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At least 343 records · Page 19

The effects of heavy particle irradiation on exploration and response to environmental change

Free radicals produced by exposure to heavy particles have been found to produce motor and cognitive behavioral toxicity effects in rats similar to those found during aging. The present research was designed to investigate the effects of exposure to 56Fe particles on the ability of male Sprague-Dawley rats to detect novel arrangements in a given environment. Using a test of spatial memory previously demonstrated to be sensitive to aging, open field activity and reaction to spatial and non-spatial changes were measured in a group that received a dose of 1.5 Gy (n=10) of 56Fe heavy particle radiation or in non-radiated controls (n=10). Animals irradiated with 1.5 Gy of 56Fe particles exhibited some age-like effects in rats tested, even though they were, for the most part, subtle. Animals took longer to enter, visited less and spent significantly less time in the middle and the center portions of the open field, independently of total frequency and duration of activity of both groups. Likewise, irradiated subjects spend significantly more time exploring novel objects placed in the open field than did controls. However, irradiated subjects did not vary from controls in their exploration patterns when objects in the open field were spatially rearranged. Thus, irradiation with a dose of 1.5 Gy of 56Fe high-energy particle radiation elicited age-like effects in general open field exploratory behavior, but did not elicit age-like effects during the spatial and non-spatial rearrangement tasks. Published by Elsevier Ltd on behalf of COSPAR.

NASA Program Biomedical Research and Countermeasur↗

PET Imaging of Leg Arteries for Determining the Input Function in PET/MRI Brain Studies Using a Compact, MRI-Compatible PET System

In this work, we used a compact, high-resolution, and magnetic resonance imaging (MRI)-compatible positron emission tomography (PET) camera (VersaPET) to assess the feasibility of measuring the image-derived input function (IDIF) from arteries in the leg with the ultimate goal of enabling fully quantitative PET brain imaging without blood sampling. We used this approach in five 18 F-FDG PET/MRI brain studies in which the input function was also acquired using the gold standard of serial arterial blood sampling. After accounting for partial volume, dispersion, and calibration effects, we compared the metabolic rates of glucose (MRglu) quantified from VersaPET IDIFs in 80 brain regions to those using the gold standard and achieved a bias and variability of <5% which is within the range of reported test-retest values for this type of study. We also achieved a strong linear relationship (R 2 >0.97) against the gold standard across regions. The results of this preliminary study are promising and support further studies to optimize methods, validate in a larger cohort, and extend to the modeling of other radiotracers.

47 OTHER INSTRUMENTATION↗

The Influence of Alkyl Spacers and Molecular Weight on the Charge Transport and Storage Properties of Oxy‐Bithiophene‐Based Conjugated Polymers

Abstract Conjugated polymers (CPs) with polar side chains can conduct electronic and ionic charges simultaneously, making them promising for bioelectronics, electrocatalysis and energy storage. Recent work showed that adding alkyl spacers between CP backbones and polar side chains improved electronic charge carrier mobility, reduced swelling and enhanced stability, without compromising ion transport. However, how alkyl spacers impact polymer backbone conformation and, subsequently, electronic properties remain unclear. In this work, we design two oxy‐bithiophene‐based CP series, each featuring progressively extended alkyl spacer lengths and two distinct molecular weight (MW) distributions. Using operando characterisations, we evaluate the (spectro)electrochemical and swelling properties of the polymer thin films, and their performance in organic field‐effect transistors and organic electrochemical transistors. Surprisingly, alkyl spacers negatively impact the hole mobility of our polymers, with higher MW amplifying this effect. Using molecular dynamics simulations, we show that it is thermodynamically favourable for adjacent non‐polar alkyl spacers to aggregate in polar electrolytes, leading to backbone twisting. Further spectroscopic measurements corroborate this prediction. Our findings demonstrate the active interactions between side chain structure, MW and electrolyte/solvent polarity in influencing polymer performance, underscoring the importance of considering solvation environment effects on polymer conformation when designing new mixed conducting CPs for electrochemical applications.

Yu, Hang [Department of Physics and Centre for Pro↗

Tomographic detection of photon pairs produced from high-energy X-rays for the monitoring of radiotherapy dosing

Measuring the radiation dose reaching a patient’s body is difficult. Here we report a technique for the tomographic reconstruction of the location of photon pairs originating from the annihilation of positron–electron pairs produced by high-energy X-rays travelling through tissue. We used Monte Carlo simulations on pre-recorded data from tissue-mimicking phantoms and from a patient with a brain tumour to show the feasibility of this imaging modality, which we named ‘pair-production tomography’, for the monitoring of radiotherapy dosing. We simulated three image-reconstruction methods, one applicable to a pencil X-ray beam scanning through a region of interest, and two applicable to the excitation of tissue volumes via broad beams (with temporal resolution sufficient to identify coincident photon pairs via filtered back projection, or with higher temporal resolution sufficient for the estimation of a photon’s time-of-flight). In addition to the monitoring of radiotherapy dosing, we show that image contrast resulting from pair-production tomography is highly proportional to the material’s atomic number. The technique may thus also allow for element mapping and for soft-tissue differentiation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Short-term adaptation of the VOR: non-retinal-slip error signals and saccade substitution

We studied short-term (30 min) adaptation of the vestibulo-ocular reflex (VOR) in five normal humans using a "position error" stimulus without retinal image motion. Both before and after adaptation a velocity gain (peak slow-phase eye velocity/peak head velocity) and a position gain (total eye movement during chair rotation/amplitude of chair motion) were measured in darkness using search coils. The vestibular stimulus was a brief ( approximately 700 ms), 15 degrees chair rotation in darkness (peak velocity 43 degrees /s). To elicit adaptation, a straight-ahead fixation target disappeared during chair movement and when the chair stopped the target reappeared at a new location in front of the subject for gain-decrease (x0) adaptation, or 10 degrees opposite to chair motion for gain-increase (x1.67) adaptation. This position-error stimulus was effective at inducing VOR adaptation, though for gain-increase adaptation the primary strategy was to substitute augmenting saccades during rotation while for gain-decrease adaptation both corrective saccades and a decrease in slow-phase velocity occurred. Finally, the presence of the position-error signal alone, at the end of head rotation, without any attempt to fix upon it, was not sufficient to induce adaptation. Adaptation did occur, however, if the subject did make a saccade to the target after head rotation, or even if the subject paid attention to the new location of the target without actually looking at it.

Non-NASA Center↗

Muscle sympathetic nerve responses to physiological changes in prostaglandin production in humans

Previous studies suggest that prostaglandins may contribute to exercise-induced increases in muscle sympathetic nerve activity (MSNA). To test this hypothesis, MSNA was measured at rest and during exercise before and after oral administration of ketoprofen, a cyclooxygenase inhibitor, or placebo. Twenty-one subjects completed two bouts of graded dynamic and isometric handgrip to fatigue. Each exercise bout was followed by 2 min of postexercise muscle ischemia. The second exercise bouts were performed after 60 min of rest in which 11 subjects were given ketoprofen (300 mg) and 10 subjects received a placebo. Ketoprofen significantly lowered plasma thromboxane B(2) in the drug group (from 36 +/- 6 to 22 +/- 3 pg/ml, P < 0.04), whereas thromboxane B(2) in the placebo group increased from 40 +/- 5 to 61 +/- 9 pg/ml from trial 1 to trial 2 (P < 0.008). Ketoprofen and placebo did not change sympathetic and cardiovascular responses to dynamic handgrip, isometric handgrip, and postexercise muscle ischemia. There was no relationship between thromboxane B(2) concentrations and MSNA or arterial pressure responses during both exercise modes. The data indicate that physiological increases or decreases in prostaglandins do not alter exercise-induced increases in MSNA and arterial pressure in humans. These findings suggest that contraction-induced metabolites other than prostaglandins mediate MSNA responses to exercise in humans.

Clinical Trial↗

The energetics and dynamics of confinement in flexible frameworks and molecular confinement

Porous frameworks form the chemical and structural basis for critical technologies in separations, catalysis, nuclear waste containment and biomedical applications. Hundreds of zeolites and metal organic frameworks (MOFs) have been synthesized, and their ability to separate and store hydrogen, methane and carbon dioxide has been investigated both experimentally and theoretically. Nevertheless, a fundamental and systematic molecular-level understanding of the thermodynamic and structural factors governing the stability and guest-host interactions in these materials lags behind focused studies of specific systems. Because the guest molecules interact with each other and with the host framework, molecular confinement is a finely balanced and complex phenomenon. The ability of the guest molecules to bind and diffuse through the pores is determined by the nature of the host framework which, in turn, responds to the nature and concentration of guest molecules and to pressure and temperature. The work explores how framework flexibility, tailored by structure, composition, temperature and pressure, is a general phenomenon, similar in nature but variable in extent, in both zeolites and MOFs and is part of a free energy landscape in which framework-guest interactions, pressure, and temperature result in changes in framework geometry and, in some cases, phase transitions. These subtle and/or pronounced changes in lattice geometry, energetics, and dynamics can play a decisive role in confinement and in differentiating the binding of molecules of similar size. The free energy landscape created by these structural changes links polymorphism, amorphization, “breathing,” “gate opening” and confinement. Specifically, the generality of such behavior arises from commonalities in lattice dynamics and energetics of frameworks containing a combination of strong rigid bonds and weaker more flexible deformation modes. Identifying and describing these common and collective phenomena is the focus of the research on a selected group of zeolites and MOFs. Structural studies using X-ray and neutron diffraction explore the mechanical functionality of these important materials, specifically how framework materials respond to changes in temperature, pressure and guest loading. These structural studies are combined with calorimetric measurements, using techniques uniquely developed in the participating laboratories, of heats of formation, heat capacities and entropies, and guest-host interactions. The experimental thermodynamic studies are complemented by inelastic neutron scattering studies of the lattice dynamics related both to framework vibrations and to guest-host interactions. The report below summarizes the work done at UC Davis, which is complemented by work done at BYU (Woodfield) and Virginia Tech (Ross).

36 MATERIALS SCIENCE↗

The energetics and dynamics of confinement in flexible frameworks and molecular confinement

Porous frameworks form the chemical and structural basis for critical technologies in separations, catalysis, nuclear waste containment and biomedical applications. Hundreds of zeolites and metal organic frameworks (MOFs) have been synthesized, and their ability to separate and store hydrogen, methane and carbon dioxide has been investigated both experimentally and theoretically. Nevertheless, a fundamental and systematic molecular-level understanding of the thermodynamic and structural factors governing the stability and guest-host interactions in these materials lags behind focused studies of specific systems. Because the guest molecules interact with each other and with the host framework, molecular confinement is a finely balanced and complex phenomenon. The ability of the guest molecules to bind and diffuse through the pores is determined by the nature of the host framework which, in turn, responds to the nature and concentration of guest molecules and to pressure and temperature. The work explores how framework flexibility, tailored by structure, composition, temperature and pressure, is a general phenomenon, similar in nature but variable in extent, in both zeolites and MOFs and is part of a free energy landscape in which framework-guest interactions, pressure, and temperature result in changes in framework geometry and, in some cases, phase transitions. These subtle and/or pronounced changes in lattice geometry, energetics, and dynamics can play a decisive role in confinement and in differentiating the binding of molecules of similar size. The free energy landscape created by these structural changes links polymorphism, amorphization, “breathing,” “gate opening” and confinement. Specifically, the generality of such behavior arises from commonalities in lattice dynamics and energetics of frameworks containing a combination of strong rigid bonds and weaker more flexible deformation modes. Identifying and describing these common and collective phenomena is the focus of the research on a selected group of zeolites and MOFs. Structural studies using X-ray and neutron diffraction explore the mechanical functionality of these important materials, specifically how framework materials respond to changes in temperature, pressure and guest loading. These structural studies are combined with calorimetric measurements, using techniques uniquely developed in the participating laboratories, of heats of formation, heat capacities and entropies, and guest-host interactions. The experimental thermodynamic studies are complemented by inelastic neutron scattering studies of the lattice dynamics related both to framework vibrations and to guest-host interactions. This research was a collaboration between UC Davis (A. Navrotsky) BYU (B. Woodfield) and Virginia Tech (N. Ross).

36 MATERIALS SCIENCE↗

Horizontal vestibuloocular reflex evoked by high-acceleration rotations in the squirrel monkey. III. Responses after labyrinthectomy

The horizontal angular vestibuloocular reflex (VOR) evoked by high-frequency, high-acceleration rotations was studied in four squirrel monkeys after unilateral labyrinthectomy. Spontaneous nystagmus was measured at the beginning and end of each testing session. During the period that animals were kept in darkness (4 days), the nystagmus at each of these times measured approximately 20 degrees /s. Within 18-24 h after return to the light, the nystagmus (measured in darkness) decreased to 2.8 +/- 1.5 degrees /s (mean +/- SD) when recorded at the beginning but was 20.3 +/- 3.9 degrees /s at the end of the testing session. The latency of the VOR measured from responses to steps of acceleration (3,000 degrees /s(2) reaching a velocity of 150 degrees /s) was 8.4 +/- 0.3 ms for responses to ipsilesional rotations and 7.7 +/- 0.4 ms for contralesional rotations. During the period that animals were kept in darkness after the labyrinthectomy, the gain of the VOR measured during the steps of acceleration was 0.67 +/- 0.12 for contralesional rotations and 0.39 +/- 0.04 for ipsilesional rotations. Within 18-24 h after return to light, the VOR gain for contralesional rotations increased to 0.87 +/- 0.08, whereas there was only a slight increase for ipsilesional rotations to 0.41 +/- 0. 06. A symmetrical increase in the gain measured at the plateau of head velocity was noted after the animals were returned to light. The VOR evoked by sinusoidal rotations of 2-15 Hz, +/-20 degrees /s, showed a better recovery of gain at lower (2-4 Hz) than at higher (6-15 Hz) frequencies. At 0.5 Hz, gain decreased symmetrically when the peak amplitude was increased from 20 to 100 degrees /s. At 10 Hz, gain was decreased for ipsilesional half-cycles and increased for contralesional half-cycles when velocity was raised from 20 to 50 degrees /s. A model incorporating linear and nonlinear pathways was used to simulate the data. Selective increases in the gain for the linear pathway accounted for the recovery in VOR gain for responses at the velocity plateau of the steps of acceleration and for the sinusoidal rotations at lower peak velocities. The increase in gain for contralesional responses to steps of acceleration and sinusoidal rotations at higher frequencies and velocities was due to an increase in the contribution of the nonlinear pathway. This pathway was driven into cutoff and therefore did not affect responses for rotations toward the lesioned side.

NASA Discipline Neuroscience↗

Modeling beta-adrenergic control of cardiac myocyte contractility in silico

The beta-adrenergic signaling pathway regulates cardiac myocyte contractility through a combination of feedforward and feedback mechanisms. We used systems analysis to investigate how the components and topology of this signaling network permit neurohormonal control of excitation-contraction coupling in the rat ventricular myocyte. A kinetic model integrating beta-adrenergic signaling with excitation-contraction coupling was formulated, and each subsystem was validated with independent biochemical and physiological measurements. Model analysis was used to investigate quantitatively the effects of specific molecular perturbations. 3-Fold overexpression of adenylyl cyclase in the model allowed an 85% higher rate of cyclic AMP synthesis than an equivalent overexpression of beta 1-adrenergic receptor, and manipulating the affinity of Gs alpha for adenylyl cyclase was a more potent regulator of cyclic AMP production. The model predicted that less than 40% of adenylyl cyclase molecules may be stimulated under maximal receptor activation, and an experimental protocol is suggested for validating this prediction. The model also predicted that the endogenous heat-stable protein kinase inhibitor may enhance basal cyclic AMP buffering by 68% and increasing the apparent Hill coefficient of protein kinase A activation from 1.0 to 2.0. Finally, phosphorylation of the L-type calcium channel and phospholamban were found sufficient to predict the dominant changes in myocyte contractility, including a 2.6x increase in systolic calcium (inotropy) and a 28% decrease in calcium half-relaxation time (lusitropy). By performing systems analysis, the consequences of molecular perturbations in the beta-adrenergic signaling network may be understood within the context of integrative cellular physiology.

Non-NASA Center↗

Comparison of sympathetic nerve responses to neck and forearm isometric exercise

PURPOSE: Although the autonomic and cardiovascular responses to arm and leg exercise have been studied, the sympathetic adjustments to exercise of the neck have not. The purpose of the present study was twofold: 1) to determine sympathetic and cardiovascular responses to isometric contractions of the neck extensors and 2) to compare sympathetic and cardiovascular responses to isometric exercise of the neck and forearm. METHODS: Muscle sympathetic nerve activity (MSNA), mean arterial pressure (MAP), and heart rate were measured in nine healthy subjects while performing isometric neck extension (INE) and isometric handgrip (IHG) in the prone position. After a 3-min baseline period, subjects performed three intensities of INE for 2.5 min each: 1) unloaded (supporting head alone), 2) 10% maximal voluntary contraction (MVC), and 3) 30% MVC, then subjects performed two intensities (10% and 30% MVC) of IHG for 2.5 min. RESULTS: Supporting the head by itself did not significantly change any of the variables. During [NE, MAP significantly increased by 10 +/- 2 and 31 +/- 4 mm Hg and MSNA increased by 67 +/- 46 and 168 +/- 36 units/30 s for 10% and 30% MVC, respectively. IHG and INE evoked similar responses at 10% MVC, but IHG elicited higher peak MAP and MSNA at 30% MVC (37 +/- 7 mm Hg (P < 0.05) and 300 +/- 48 units/30 s (P < 0.01) for IHG, respectively). CONCLUSIONS: The data indicate that INE can elicit marked increases in MSNA and cardiovascular responses but that it evokes lower peak responses as compared to IHG. We speculate that possible differences in muscle fiber type composition, muscle mass, and/or muscle architecture of the neck and forearm are responsible for these differences in peak responses.

NASA Discipline Neuroscience↗

Error, stress, and teamwork in medicine and aviation: cross sectional surveys

OBJECTIVES: To survey operating theatre and intensive care unit staff about attitudes concerning error, stress, and teamwork and to compare these attitudes with those of airline cockpit crew. DESIGN:: Cross sectional surveys. SETTING:: Urban teaching and non-teaching hospitals in the United States, Israel, Germany, Switzerland, and Italy. Major airlines around the world. PARTICIPANTS:: 1033 doctors, nurses, fellows, and residents working in operating theatres and intensive care units and over 30 000 cockpit crew members (captains, first officers, and second officers). MAIN OUTCOME MEASURES:: Perceptions of error, stress, and teamwork. RESULTS:: Pilots were least likely to deny the effects of fatigue on performance (26% v 70% of consultant surgeons and 47% of consultant anaesthetists). Most pilots (97%) and intensive care staff (94%) rejected steep hierarchies (in which senior team members are not open to input from junior members), but only 55% of consultant surgeons rejected such hierarchies. High levels of teamwork with consultant surgeons were reported by 73% of surgical residents, 64% of consultant surgeons, 39% of anaesthesia consultants, 28% of surgical nurses, 25% of anaesthetic nurses, and 10% of anaesthetic residents. Only a third of staff reported that errors are handled appropriately at their hospital. A third of intensive care staff did not acknowledge that they make errors. Over half of intensive care staff reported that they find it difficult to discuss mistakes. CONCLUSIONS: Medical staff reported that error is important but difficult to discuss and not handled well in their hospital. Barriers to discussing error are more important since medical staff seem to deny the effect of stress and fatigue on performance. Further problems include differing perceptions of teamwork among team members and reluctance of senior theatre staff to accept input from junior members.

Non-NASA Center↗

Differences in the hemodynamic response to event-related motor and visual paradigms as measured by near-infrared spectroscopy

Several current brain imaging techniques rest on the assumption of a tight coupling between neural activity and hemodynamic response. The nature of this neurovascular coupling, however, is not completely understood. There is some evidence for a decoupling of these processes at the onset of neural activity, which manifests itself as a momentary increase in the relative concentration of deoxyhemoglobin (HbR). The existence of this early component of the hemodynamic response function, however, is controversial, as it is inconsistently found. Near infrared spectroscopy (NIRS) allows quantification of levels of oxyhemoglobin (HbO(2)) and HbR during task performance in humans. We acquired NIRS data during performance of simple motor and visual tasks, using rapid-presentation event-related paradigms. Our results demonstrate that rapid, event-related NIRS can provide robust estimates of the hemodynamic response without artifacts due to low-frequency signal components, unlike data from blocked designs. In both the motor and visual data the onset of the increase in HbO(2) occurs before HbR decreases, and there is a poststimulus undershoot. Our results also show that total blood volume (HbT) drops before HbO(2) and undershoots baseline, raising a new issue for neurovascular models. We did not find early deoxygenation in the motor data using physiologically plausible values for the differential pathlength factor, but did find one in the visual data. We suggest that this difference, which is consistent with functional magnetic resonance imaging (fMRI) data, may be attributable to different capillary transit times in these cortices.

NASA Program Biomedical Research and Countermeasur↗

Impact of p53 status on heavy-ion radiation-induced micronuclei in circulating erythrocytes

Transgenic mice that differed in their p53 genetic status were exposed to an acute dose of highly charged and energetic (HZE) iron particle radiation. Micronuclei (MN) in two distinct populations of circulating peripheral blood erythrocytes, the immature reticulocytes (RETs) and the mature normochromatic erythrocytes (NCEs), were measured using a simple and efficient flow cytometric procedure. Our results show significant elevation in the frequency of micronucleated RETs (%MN-RETs) at 2 and 3 days post-radiation. At 3 days post-irradiation, the magnitude of the radiation-induced MN-RET was 2.3-fold higher in the irradiated p53 wild-type animals compared to the unirradiated controls, 2.5-fold higher in the p53 hemizygotes and 4.3-fold higher in the p53 nullizygotes. The persistence of this radiation-induced elevation of MN-RETs is dependent on the p53 genetic background of the animal. In the p53 wild-type and p53 hemizygotes, %MN-RETs returned to control levels by 9 days post-radiation. However, elevated levels of %MN-RETs in p53 nullizygous mice persisted beyond 56 days post-radiation. We also observed elevated MN-NCEs in the peripheral circulation after radiation, but the changes in radiation-induced levels of MN-NCEs appear dampened compared to those of the MN-RETs for all three strains of animals. These results suggest that the lack of p53 gene function may play a role in the iron particle radiation-induced genomic instability in stem cell populations in the hematopoietic system.

NASA Discipline Radiation Health↗

Application of real-time radiation dosimetry using a new silicon LET sensor

A new type of real-time radiation monitoring device, RRMD-III, consisting of three double-sided silicon strip detectors (DSSDs), has been developed and tested on-board the Space Shuttle mission STS-84. The test succeeded in measuring the linear energy transfer (LET) distribution over the range of 0.2 keV/micrometer to 600 keV/micrometer for 178 h. The Shuttle cruised at an altitude of 300 to 400 km and an inclination angle of 51.6 degrees for 221.3 h, which is equivalent to the International Space Station orbit. The LET distribution obtained for particles was investigated by separating it into galactic cosmic ray (GCR) particles and trapped particles in the South Atlantic Anomaly (SAA) region. The result shows that the contribution in dose-equivalent due to GCR particles is almost equal to that from trapped particles. The total absorbed dose rate during the mission was 0.611 mGy/day; the effective quality factor, 1.64; and the dose equivalent rate, 0.998 mSv/day. The average absorbed dose rates are 0.158 mGy/min for GCR particles and 3.67 mGy/min for trapped particles. The effective quality factors are 2.48 for GCR particles and 1.19 for trapped particles. The absorbed doses obtained by the RRMD-III and a conventional method using TLD (Mg(2)SiO(4)), which was placed around the RRMD-III were compared. It was found that the TLDs showed a lower efficiency, just 58% of absorbed dose registered by the RRMD-III.

NASA Discipline Radiation Health↗

Inducing jet-lag in older people: directional asymmetry

Twenty healthy elderly subjects (12 female, 8 male; mean age 81 years, range 67-87 years) each experienced a 15-day time isolation protocol in which they lived individually in a special laboratory apartment in which sleep and circadian rhythm measures could be taken. There were two experiments: one (6 females, 4 males) involved a 6-h phase advance of the sleep/wake cycle, and the other (6 females, 4 males) a 6-h phase delay. Each started with 5 baseline days, immediately followed by the phase shift. The subject was then held to the phase shifted routine for the remainder of the study. Rectal temperatures were recorded minute-by-minute throughout the entire experiment and each night of sleep was recorded using polysomnography. A directional asymmetry in phase-shift effects was apparent, with significantly more sleep disruption and circadian rhythm amplitude disruption after the phase advance than after the phase delay. Sleep disruption was reflected in reduced time spent asleep, and in changed REM latency, which increased in the phase advance direction but decreased in the phase delay direction. Although the phase advance led to a significant increase in wakefulness in the first half of the night, the phase delay did not lead to an equivalent increase in wakefulness during the second half of the night. Examination of both raw and 'demasked' circadian rectal temperature rhythms confirmed that phase adjustment was slow in both directions, but was less slow (and more monotonic) after the phase delay than after the phase advance. Subjective alertness suffered more disruption after the phase advance than after the phase delay.

NASA Discipline Regulatory Physiology↗

Comparing Theoretically Scaled Biomechanical Models

BACKGROUND An investigation into incorporating space suit aspects required a 50th-percentile male model which was not part of the existing dataset of models. Previously, theoretical models for 5th-percentile female and 95th-percentile male were created utilizing a scaled test subject as close as possible to the target height and weight. Scaling factors were created by taking the height ratio and applying it uniformly to the model body segments, then fine tuning to ensure the theoretical model’s height is as expected. This study was initiated to examine the existing method of isometrically scaling in OpenSim [1,2] and to create alternative methods which do not rely on an existing subject being close in height and weight to the theoretical model of interest. Generating a theoretical biomechanical model provides additional abilities without the reliance on available OpenSim models or real subjects. Gained abilities include creating different percentile models and attaining representative anthropometry for any target height/weight, such as targeting specific crew populations or gaps within the current dataset. METHODS AND RESULTS This study includes 3 methods for generating the theoretical model; utilizing the modified unscaled OpenSim Full Body Rajagopal Model (FBRM) [3,4], a dataset of scaled OpenSim models, and existing scaling factors from Dumas et al. [5]. All methods use the Anthropometric Survey of US Army Personnel (ANSUR II) [6] as an input of necessary anthropometric measurements. The following measurements are retrieved from the ANSUR II collection: mass, stature, cervicale height, acromial height, axilla height, waist height, trochanterion height, lateral femoral epicondyle height, lateral malleolus height, acromion-radiale length, radiale-stylion length, palm length, ball of foot length, bicristal breadth, bimalleolar breadth. Some of the measurements are direct segment lengths and others are utilized to derive segment lengths. Height, weight, and age ranges are the required inputs to parse the collection for a mean value of the measurements. A simple iterative process may be necessary for the output of mean mass and stature consistent with the theoretical model of interest. In some cases, one may specify exact values instead of a range but that is dependent upon whether those exact values pertain to a single subject from the ANSUR II collection. Equations from Dumas et al. were used to calculate scaling factors for the two methods that utilize OpenSim scaled and unscaled models. In the third method, Dumas’ scaling factors were used directly instead of generating our own. After scaling factors are achieved, they are applied along with the mass and segment lengths retrieved from ANSUR II in order to calculate the segment mass, Center of Mass (CoM), mass Moment of Inertia (MoI), and the joint location in the parent frame. The theoretical models from the different methods were compared to the previous existing method of isometrically scaling in OpenSim, as well as the standards found in NASA STD-3000 [7] and the NASA Human Integration Design Handbook [8]. The whole-body center of mass is the main comparison performed between the models and the standards. The body segment mass properties were also compared when possible. In some cases, the standards do not provide complete data, or the center of mass location is not provided with respect to the appropriate joint coordinate system. For a 50th-percentile male subject, results from isometric scaling in OpenSim and the method utilizing the unscaled FBRM were compared to the standards in NASA STD-3000. According to the standard, the whole-body vertical CoM location was taken from the head vertex to the CoM. The standards provide 80.2 cm for the CoM vertical component whereas isometric scaling in OpenSim and utilizing the unscaled FBRM provide 82.2 and 82.3 cm, respectively. Through definition, the whole-body CoM in the medial/lateral direction agreed across the models. Investigation is on-going to clearly identify the reference point pertaining to dorsal/ventral whole-body CoM position in standards and relate that to the theoretical models. REFERENCES [1] Delp, S.L., et al., “OpenSim: Open-source Software to Create and Analyze Dynamic Simulations of Movement”, IEEE Transactions on Biomedical Engineering, (2007). [2] Seth, A., Hicks J.L., Uchida, T.K., Habib, A., Dembia, C.L., Dunne, J.J., Ong, C.F., DeMers, M.S., Rajagopal, A., Millard, M., Hamner, S.R., Arnold, E.M., Yong, J.R., Lakshmikanth, S.K., Sherman,n M.A., Delp, S.L. OpenSim: Simulating musculoskeletal dynamics and neuromuscular control to study human and animal movement. Plos Computational Biology, 14(7). (2018) [3] R. K. Huffman, W. K. Thompson, C. A. Gallo, L. J. Quiocho, “Improvement of Scaling and Inverse Kinematic Results with Additional Upper Body Joints Added to Opensim Rajagopal Model”, NASA Human Research Program Investigator’s Workshop, (2019). [4] Huffman R.K., Thompson W., Gallo C., “Modified OpenSim Rajagopal Full Body Model”, New Technology Report, MSC-26872-1. (August 2020). [5] Dumas R., Cheze L. and Verriest J., 2007. “Adjustments to McConville et al. and Young et al. body segment inertial parameters”. Journal of Biomechanics 40, pp. 543-553 [6] Gordon C.C., 2012 “Anthropometric Survey of U.S. Army Personnel: Methods and Summary Statistics”, US Army Natick Soldier RD&E Center. [7] NASA STD-3000/REV-B, 1995. “The Man-System Integration Standards” [8] NASA/SP-2010-3407/REV-1, 2014. “The Human Integration Design Handbook (HIDH)”

F N Matari↗

Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency

BACKGROUND: Orthostatic intolerance is a syndrome characterized by lightheadedness, fatigue, altered mentation, and syncope and associated with postural tachycardia and plasma norepinephrine concentrations that are disproportionately high in relation to sympathetic outflow. We tested the hypothesis that impaired functioning of the norepinephrine transporter contributes to the pathophysiologic mechanism of orthostatic intolerance. METHODS: In a patient with orthostatic intolerance and her relatives, we measured postural blood pressure, heart rate, plasma catecholamines, and systemic norepinephrine spillover and clearance, and we sequenced the norepinephrine-transporter gene and evaluated its function. RESULTS: The patient had a high mean plasma norepinephrine concentration while standing, as compared with the mean (+/-SD) concentration in normal subjects (923 vs. 439+/-129 pg per milliliter [5.46 vs. 2.59+/-0.76 nmol per liter]), reduced systemic norepinephrine clearance (1.56 vs. 2.42+/-0.71 liters per minute), impairment in the increase in the plasma norepinephrine concentration after the administration of tyramine (12 vs. 56+/-63 pg per milliliter [0.07 vs. 0.33+/-0.37 pmol per liter]), and a disproportionate increase in the concentration of plasma norepinephrine relative to that of dihydroxyphenylglycol. Analysis of the norepinephrine-transporter gene revealed that the proband was heterozygous for a mutation in exon 9 (encoding a change from guanine to cytosine at position 237) that resulted in more than a 98 percent loss of function as compared with that of the wild-type gene. Impairment of synaptic norepinephrine clearance may result in a syndrome characterized by excessive sympathetic activation in response to physiologic stimuli. The mutant allele in the proband's family segregated with the postural heart rate and abnormal plasma catecholamine homeostasis. CONCLUSIONS: Genetic or acquired deficits in norepinephrine inactivation may underlie hyperadrenergic states that lead to orthostatic intolerance.

Non-NASA Center↗