ALBERT

Beschreibung: The goal of the Functional Task Test study is to determine the effects of space flight on functional tests that are representative of high priority exploration mission tasks and to identify the key underlying physiological factors that contribute to decrements in performance. Ultimately this information will be used to assess performance risks and inform the design of countermeasures for exploration class missions. We are currently conducting studies on both ISS crewmembers and on subjects experiencing 70 days of 6 degrees head-down bed-rest as an analog for space flight. Bed-rest provides the opportunity for us to investigate the role of prolonged axial body unloading in isolation from the other physiological effects produced by exposure to the microgravity environment of space flight. This allows us to parse out the contribution of the body unloading component on functional performance. In this on-going study both ISS crewmembers and bed-rest subjects were tested using an interdisciplinary protocol that evaluated functional performance and related physiological changes before and after 6 months in space and 70 days of 6 head-down bed-rest, respectively. Functional tests included ladder climbing, hatch opening, jump down, manual manipulation of objects and tool use, seat egress and obstacle avoidance, recovery from a fall, and object translation tasks. Crewmembers were tested three times before flight, and on 1, 6 and 30 days after landing. Bed-rest subjects were tested three times before bed-rest and immediately after getting up from bed-rest as well as 1, 6 and 12 days after reambulation. A comparison of bed-rest and space flight data showed a significant concordance in performance changes across all functional tests. Tasks requiring a greater demand for dynamic control of postural equilibrium (i.e. fall recovery, seat egress/obstacle avoidance during walking, object translation, jump down) showed the greatest decrement in performance. Functional tests with reduced requirements for postural stability (i.e. hatch opening, ladder climb, manual manipulation of objects and tool use) showed little reduction in performance. Bed-rest results indicate that body support unloading experienced during space flight plays a central role in postflight alteration of functional task performance. These data point to the importance of providing axial body loading as a central component of an inflight training system that will integrate cardiovascular, resistance and sensorimotor adaptability training modalities into a single interdisciplinary countermeasure system.

Beschreibung: Pre- and post-flight dynamometry is performed on International Space Station crewmembers to characterize microgravity-induced strength changes. Strength is not assessed in flight due to hardware limitations and there is poor understanding of the time course of in-flight changes. PURPOSE: To assess the reliability of a prototype dynamometer, the X1 Exoskeleton (EXO) and its agreement with a Biodex System 4 (BIO). METHODS: Eight subjects (4 M/4 F) completed 2 counterbalanced testing sessions of knee extension/flexion (KE/KF), 1 with BIO and 1 with EXO, with repeated measures within each session in normal gravity. Test-retest reliability (test 1 and 2) and device agreement (BIO vs. EXO) were evaluated. Later, to assess device agreement for ankle plantarflexion (PF), 10 subjects (4 M/6 F) completed 3 test conditions (BIO, EXO, and BIOEXO); BIOEXO was a hybrid condition comprised of the Biodex dynamometer motor and the X1 footplate and ankle frame. Ankle comparisons were: BIO vs. BIOEXO (footplate differences), BIOEXO vs. EXO (motor differences), and BIO vs. EXO (all differences). Reliability for KE/KF was determined by intraclass correlation (ICC). Device agreement was assessed with: 1) repeated measures ANOVA, 2) a measure of concordance (rho), and 3) average difference. RESULTS: ICCs for KE/KF were 0.99 for BIO and 0.96 to 0.99 for EXO. Agreement was high for KE (concordance: 0.86 to 0.95; average differences: -7 to +9 Nm) and low to moderate for KF (concordance: 0.64 to 0.78; average differences: -4 to -29 Nm, P〈0.05). BIO vs. BIOEXO PF concordance ranged from 0.89 to 0.92 and mean differences ranged from -9 to +3 Nm (BIO 〈 BIOEXO). BIOEXO vs. EXO PF concordance ranged from 0.73 to 0.80 while mean differences were -18 to -36 Nm (BIOEXO 〈 EXO, P〈0.05). PF concordance for BIO vs. EXO was slightly lower (0.61 to 0.84) and mean differences were greater (-27 to -33 Nm; BIO 〈 EXO, P〈0.05). CONCLUSION: BIO and EXO were similarly reliable for KE and KF. KE measures produced high agreement between devices; KF did not. For ankle PF, torque differences due to the two footplates were small. However, the X1 motor reports greater torques than the Biodex motor during PF. This first prototype provides proof of concept for a reliable, robotic-based exoskeleton to perform portable dynamometry for large muscle groups of the lower body.

Beschreibung: Exercise prescriptions completed by International Space Station (ISS) crewmembers are typically based upon evidence obtained during ground-based investigations, with the assumption that the results of long-term training in weightlessness will be similar to that attained in normal gravity. Coupled with this supposition are the assumptions that exercise motions and external loading are also similar between gravitational environments. Normal control of locomotion is dependent upon learning patterns of muscular activation and requires continual monitoring of internal and external sensory input [1]. Internal sensory input includes signals that may be dependent on or independent of gravity. Bernstein hypothesized that movement strategy planning and execution must include the consideration of segmental weights and inertia [2]. Studies of arm movements in microgravity showed that individuals tend to make errors but that compensation strategies result in adaptations, suggesting that control mechanisms must include peripheral information [3-5]. To date, however, there have been no studies examining a gross motor activity such as running in weightlessness other than using microgravity analogs [6-8]. The objective of this evaluation was to collect biomechanical data from crewmembers during treadmill exercise before and during flight. The goal was to determine locomotive biomechanics similarities and differences between normal and weightless environments. The data will be used to optimize future exercise prescriptions. This project addresses the Critical Path Roadmap risks 1 (Accelerated Bone Loss and Fracture Risk) and 11 (Reduced Muscle Mass, Strength, and Endurance). Data were collected from 7 crewmembers before flight and during their ISS missions. Before launch, crewmembers performed a single data collection session at the NASA Johnson Space Center. Three-dimensional motion capture data were collected for 30 s at speeds ranging from 1.5 to 9.5 mph in 0.5 mph increments with a 12-camera system. During flight, each crewmember completed up to 6 data collection sessions spread across their missions, performing their normal exercise prescription for the test day, resulting in varying data collection protocols between sessions. Motion data were collected by a single HD video camera positioned to view the crewmembers' left side, and tape markers were placed on their feet, legs, and neck on specific landmarks. Before data collection, the crewmembers calibrated the video camera. Video data were collected during the entire exercise session at 30 Hz. Kinematic data were used to determine left leg hip, knee, and ankle range of motion and contact time, flight time, and stride time for each stride. 129 trials in weightlessness were analyzed. Mean time-normalized strides were found for each trial, and cross-correlation procedures were used to examine the strength and direction of relationships between segment movement pattern timing in each gravitational condition. Cross-correlation analyses between gravitational conditions revealed highly consistent movement patterns at each joint. Peak correlation coefficients occurred at 0% phase, indicating there were no lags in movement timing. Joint ranges of motion were similar between gravitational conditions, with some slight differences between subjects. Motion patterns in weightlessness were highly consistent at a given speed with those occurring in 1G, indicating that despite differing sensory input, subjects maintain running kinematics. The data suggest that individuals are capable of compensating for loss of limb weight when creating movement strategies. These results have important implications for creating training programs for use in weightlessness as practitioners can have greater confidence in running motions transferring across gravitational environments. Furthermore, these results have implications for use by researchers investigating motor control mechanisms and investigating hypotheses related to movement strategies when using sensory input that is dependent upon gravity.

Beschreibung: An intranasal gel formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness. The bioavailability and pharmacokinetics (PK) were evaluated under the Food and Drug Administration guidelines for clinical trials for an Investigative New Drug (IND). The aim of this project was to develop a PK model that can predict the relationship between plasma, saliva and urinary scopolamine concentrations using data collected from the IND clinical trial with INSCOP. METHODS: Twelve healthy human subjects were administered three dose levels (0.1, 0.2 and 0.4 mg) of INSCOP. Serial blood, saliva and urine samples were collected between 5 min to 24 h after dosing and scopolamine concentrations measured by using a validated LC-MS-MS assay. Pharmacokinetic Compartmental models, using actual dosing and sampling times, were built using Phoenix (version 1.2). Model discrimination was performed, by minimizing the Akaike Information Criteria (AIC), maximizing the coefficient of determination (r) and by comparison of the quality of fit plots. RESULTS: The best structural model to describe scopolamine disposition after INSCOP administration (minimal AIC =907.2) consisted of one compartment for plasma, saliva and urine respectively that were inter-connected with different rate constants. The estimated values of PK parameters were compiled in Table 1. The model fitting exercises revealed a nonlinear PK for scopolamine between plasma and saliva compartments for K21, Vmax and Km. CONCLUSION: PK model for INSCOP was developed and for the first time it satisfactorily predicted the PK of scopolamine in plasma, saliva and urine after INSCOP administration. Using non-linear PK yielded the best structural model to describe scopolamine disposition between plasma and saliva compartments, and inclusion of non-linear PK resulted in a significant improved model fitting. The model can be utilized to predict scopolamine plasma concentration using saliva and/or urine data that allows non-invasive assessment of pharmacotherapeutics of scopolamine in space and other remote environments without requiring blood sampling.

Beschreibung: The goals of the Functional Task Test (FTT) study were to determine the effects of space flight on functional tests that are representative of high priority exploration mission tasks and to identify the key underlying physiological factors that contribute to decrements in performance. Ultimately this information will be used to assess performance risks and inform the design of countermeasures for exploration class missions. We have previously shown that for Shuttle, ISS and bed rest subjects functional tasks requiring a greater demand for dynamic control of postural equilibrium (i.e. fall recovery, seat egress/obstacle avoidance during walking, object translation, jump down) showed the greatest decrement in performance. Functional tests with reduced requirements for postural stability (i.e. hatch opening, ladder climb, manual manipulation of objects and tool use) showed little reduction in performance. These changes in functional performance were paralleled by similar decrements in sensorimotor tests designed to specifically assess postural equilibrium and dynamic gait control. The bed rest analog allows us to investigate the impact of axial body unloading in isolation on both functional tasks and on the underlying physiological factors that lead to decrements in performance and then compare them with the results obtained in our space flight study. These results indicate that body support unloading experienced during space flight plays a central role in postflight alteration of functional task performance. Given the importance of body-support loading we set out to determine if there is a relationship between the load experienced during inflight treadmill exercise (produced by a harness and bungee system) and postflight functional performance. ISS crewmembers (n=13) were tested using the FTT protocol before and after 6 months in space. Crewmembers were tested three times before flight, and on 1, 6, and 30 days after landing. To determine how differences in body-support loading experienced during inflight treadmill exercise impacts postflight functional performance, the loading history for each subject during inflight treadmill (T2) exercise was correlated with postflight measures of performance. Crewmembers who walked on the treadmill with higher pull-down loads had less decrement in postflight postural stability and dynamic locomotor control than those subjects who exercised with lighter loads. These data point to the importance of providing significant body loading during inflight treadmill exercise. This and the addition of specific balance training may further mitigate decrements in critical mission tasks that require dynamic postural stability and mobility. Inflight treadmill exercise provides a multi-disciplinary platform to provide sensorimotor, aerobic and bone mechanical stimuli benefits. Forward work will focus on the development of an inflight training system that will integrate aerobic, resistive and balance training modalities into a single interdisciplinary countermeasure system for exploration class missions.

Beschreibung: The goals of the Functional Task Test (FTT) study were to determine the effects of space flight on functional tests that are representative of high priority exploration mission tasks and to identify the key underlying physiological factors that contribute to decrements in performance. Ultimately this information will be used to assess performance risks and inform the design of countermeasures for exploration class missions. We have previously shown that for Shuttle, ISS and bed rest subjects, functional tasks requiring a greater demand for dynamic control of postural equilibrium (i.e. fall recovery, seat egress/obstacle avoidance during walking, object translation, jump down) showed the greatest decrement in performance. Functional tests with reduced requirements for postural stability (i.e. hatch opening, ladder climb, manual manipulation of objects and tool use) showed little reduction in performance. These changes in functional performance were paralleled by similar decrements in sensorimotor tests designed to specifically assess postural equilibrium and dynamic gait control. The bed rest analog allows us to investigate the impact of axial body unloading in isolation on both functional tasks and on the underlying physiological factors that lead to decrements in performance and then compare them with the results obtained in our space flight study. These results indicate that body support unloading experienced during space flight plays a central role in postflight alteration of functional task performance. These data also support the concept that space flight may cause central adaptation of converging body-load somatosensory and vestibular input during gravitational transitions [1]. Therefore, we conclude that providing significant body-support loading during inflight treadmill along with balance training is necessary to mitigate decrements in critical mission tasks that require dynamic postural stability and mobility. Data obtained from space flight and bed rest support the notion that in-flight treadmill exercise, in addition to providing aerobic exercise and mechanical stimuli to the bone, also has a number of sensorimotor benefits by providing: 1) A balance challenge during locomotion requiring segmental coordination in response to a downward force. 2) Body-support loading during performance of a full-body active motor task. 3) Oscillatory stimulation of the otoliths and synchronized periodic foot impacts that facilitate the coordination of gait motions and tune the full-body gaze control system. 4) Appropriate sensory input (foot tactile input, muscle and tendon stretch input) to spinal locomotor central pattern generators required for the control of locomotion. Forward work will focus on a follow-up bed rest study that incorporates aerobic and resistance exercise with a treadmill balance and gait training system that can serve as an integrated interdisciplinary countermeasure system for future exploration class missions.

Beschreibung: An intranasal gel formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness. The bioavailability and pharmacokinetics (PK) were evaluated under the Food and Drug Administration guidelines for clinical trials with an Investigative New Drug (IND) protocol. The aim of this project was to develop a PK model that can predict the relationship between plasma, saliva and urinary scopolamine concentrations using data collected from the IND clinical trials with INSCOP. Methods: Twelve healthy human subjects were administered three dose levels (0.1, 0.2 and 0.4 mg) of INSCOP. Serial blood, saliva and urine samples were collected between 5 min and 24 h after dosing and scopolamine concentrations were measured by using a validated LCMSMS assay. Pharmacokinetic Compartmental models, using actual dosing and sampling times, were built using Phoenix (version 1.2). Model selection was based on the likelihood ratio test on the difference of criteria (2LL) and comparison of the quality of fit plots. Results: The best structural model for INSCOP (minimal 2LL= 502.8) was established. It consisted of one compartment each for plasma, saliva and urine, respectively, which were connected with linear transport processes except the nonlinear PK process from plasma to saliva compartment. The bestfit estimates of PK parameters from individual PK compartmental analysis and Population PK model analysis were shown in Tables 1 and 2, respectively. Conclusion: A population PK model that could predict population and individual PK of scopolamine in plasma, saliva and urine after dosing was developed and validated. Incorporating a nonlinear transfer from plasma to saliva compartments resulted in a significantly improved model fitting. The model could be used to predict scopolamine plasma concentrations from salivary and urinary drug levels, allowing noninvasive therapeutic monitoring of scopolamine in space and other remote environments.

Beschreibung: Astronauts perform physically demanding tasks and risk incurring musculoskeletal injuries during both groundbased training and missions. Increased injury rates throughout the history of the U.S. space program have been attributed to numerous factors, including an aging astronaut corps, increased Weightless Environment Training Facility (WETF) and Neutral Buoyancy Laboratory (NBL) training to construct the International Space Station, and improved clinical operations that promote injury prevention and reporting. With NASA program changes through the years (including retirement of the Shuttle program) and an improved training environment (including a new astronaut gym), there is no surveillance program to systematically track injury rates. A limited number of research projects have been conducted over the past 20 years to evaluate musculoskeletal injuries: (1) to evaluate orthopedic injuries from 1987 to 1995, (2) to describe upper extremity injuries, (3) to evaluate EVA spacesuit training related injuries, and (4) to evaluate in-flight musculoskeletal injuries. Nevertheless, there has been no consistently performed comprehensive assessment of musculoskeletal injuries among astronauts. The Barell Injury Diagnosis Matrix was introduced at the 2001 meeting of the International Collaborative Effort (ICE) on Injury Statistics. The Matrix proposes a standardized method of classifying body region by nature of injury. Diagnoses are coded using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) coding system. The purpose of this study is to assess the usefulness and complexity of the Barell Injury Diagnosis Matrix to classify and track musculoskeletal injuries among NASA astronauts.

Beschreibung: Astronauts experience sensorimotor disturbances during the initial exposure to microgravity and during the re-adapation phase following a return to an earth-gravitational environment. These alterations may disrupt the ability to perform mission critical functional tasks requiring ambulation, manual control and gaze stability. Interestingly, astronauts who return from space flight show substantial differences in their abilities to readapt to a gravitational environment. The ability to predict the manner and degree to which individual astronauts would be affected would improve the effectiveness of countermeasure training programs designed to enhance sensorimotor adaptability. For such an approach to succeed, we must develop predictive measures of sensorimotor adaptability that will allow us to foresee, before actual space flight, which crewmembers are likely to experience the greatest challenges to their adaptive capacities. The goals of this project are to identify and characterize this set of predictive measures that include: 1) behavioral tests to assess sensory bias and adaptability quantified using both strategic and plastic-adaptive responses; 2) imaging to determine individual brain morphological and functional features using structural magnetic resonance imaging (MRI), diffusion tensor imaging, resting state functional connectivity MRI, and sensorimotor adaptation task-related functional brain activation; 3) genotype markers for genetic polymorphisms in Catechol-O-Methyl Transferase, Dopamine Receptor D2, Brain-derived neurotrophic factor and genetic polymorphism of alpha2-adrenergic receptor that play a role in the neural pathways underlying sensorimotor adaptation. We anticipate these predictive measures will be significantly correlated with individual differences in sensorimotor adaptability after long-duration space flight and an analog bed rest environment. We will be conducting a retrospective study leveraging data already collected from relevant ongoing/completed bed rest and space flight studies. These data will be combined with predictor metrics that will be collected prospectively - behavioral, brain imaging and genomic measures; from these returning subjects to build models for predicting post-mission (bed rest - non-astronauts or space flight - astronauts) adaptive capability as manifested in their outcome measures. Comparisons of model performance will allow us to better design and implement sensorimotor adaptability training countermeasures that are customized for each crewmember's sensory biases, adaptive capacity, brain structure and functional capacities, and genetic predispositions against decrements in post-mission adaptive capability. This ability will allow more efficient use of crew time during training and will optimize training prescriptions for astronauts to ensure expected outcomes.

Beschreibung: In an effort to improve cardiovascular disease (CVD) risk prediction, this analysis evaluates and compares the applicability of multiple CVD risk scores to the NASA Astronaut Corps which is extremely healthy at selection.