ALBERT

Description: Current human space travel consists primarily of long-duration missions onboard the International Space Station (ISS), but in the future may include exploration-class missions to nearby asteroids, Mars, or its moons. These missions will expose astronauts to increased risk of oxidative and inflammatory damage from a variety of sources, including radiation, psychological stress, reduced physical activity, diminished nutritional status, and hyperoxic exposure during extravehicular activity. Evidence exists that increased oxidative stress and inflammation can accelerate the development of atherosclerosis.

Description: Future exploration missions will be the first time humanity travels beyond Low Earth Orbit (LEO) since the Apollo program, taking us to cis-lunar space, interplanetary space, and Mars. These long-duration missions will cover vast distances, severely constraining opportunities for emergency evacuation to Earth and cargo resupply opportunities. Communication delays and blackouts between the crew and Mission Control will eliminate reliable, real-time telemedicine consultations. As a result, compared to current LEO operations onboard the International Space Station, exploration mission medical care requires an integrated medical system that provides additional in-situ capabilities and a significant increase in crew autonomy. The Medical System Concept of Operations for Mars Exploration Missions illustrates how a future NASA Mars program could ensure appropriate medical care for the crew of this highly autonomous mission. This Concept of Operations document, when complete, will document all mission phases through a series of mission use case scenarios that illustrate required medical capabilities, enabling the NASA Human Research Program (HRP) Exploration Medical Capability (ExMC) Element to plan, design, and prototype an integrated medical system to support human exploration to Mars.

Description: Congestion is commonly reported during spaceflight, and most crewmembers have reported using medications for congestion during International Space Station (ISS) missions. Although congestion has been attributed to fluid shifts during spaceflight, fluid status reaches equilibrium during the first week after launch while congestion continues to be reported throughout long duration missions. Congestion complaints have anecdotally been reported in relation to ISS CO2 levels; this evaluation was undertaken to determine whether or not an association exists. METHODS: Reported headaches, congestion symptoms, and CO2 levels were obtained for ISS expeditions 2-31, and time-weighted means and single-point maxima were determined for 24-hour (24hr) and 7-day (7d) periods prior to each weekly private medical conference. Multiple imputation addressed missing data, and logistic regression modeled the relationship between probability of reported event of congestion or headache and CO2 levels, adjusted for possible confounding covariates. The first seven days of spaceflight were not included to control for fluid shifts. Data were evaluated to determine the concentration of CO2 required to maintain the risk of congestion below 1% to allow for direct comparison with a previously published evaluation of CO2 concentrations and headache. RESULTS: This study confirmed a previously identified significant association between CO2 and headache and also found a significant association between CO2 and congestion. For each 1-mm Hg increase in CO2, the odds of a crew member reporting congestion doubled. The average 7-day CO2 would need to be maintained below 1.5 mmHg to keep the risk of congestion below 1%. The predicted probability curves of ISS headache and congestion curves appear parallel when plotted against ppCO2 levels with congestion occurring at approximately 1mmHg lower than a headache would be reported. DISCUSSION: While the cause of congestion is multifactorial, this study showed congestion is associated with CO2 levels on ISS. Data from additional expeditions could be incorporated to further assess this finding. CO2 levels are also associated with reports of headaches on ISS. While it may be expected for astronauts with congestion to also complain of headaches, these two symptoms are commonly mutually exclusive. Furthermore, it is unknown if a temporal CO2 relationship exists between congestion and headache on ISS. CO2 levels were time-weighted for 24hr and 7d, and thus the time course of congestion leading to headache was not assessed; however, congestion could be an early CO2-related symptom when compared to headache. Future studies evaluating the association of CO2-related congestion leading to headache would be difficult due to the relatively stable daily CO2 levels on ISS currently, but a systematic study could be implemented on-orbit if desired.

Description: This panel presents recent updates to and a comprehensive overview of the operational medical support provided to ISS crewmembers in Star City, Russia and Kazakhstan as part of UTMB/KBRwyle's Human Health & Performance contract. With the current Soyuz training flow, physician support is required for nominal training evolutions involving pressure changes or other potential physical risks detailed in this presentation. In addition, full-time physician presence in Star City helps to address the disparity in access to health care in these relatively remote practice areas, while also developing and maintaining relationships with host nation resources. A unique part of standard training in Russia also involves survival training in both winter and water environments; logistic details and medical impacts of each of these training scenarios will be discussed. Following support of a successful training flow, UTMB/KBRwyle's Star City Medical Support Group (SCMSG) is also responsible for configuring medical packs in support of Soyuz launches and landings; we will present the rationale for current pack contents within the context of specific operational needs. With respect to contingency events, the group will describe their preparedness to respond appropriately by activating both local and global resources as necessary, detailing a specialized subset of the group who continually work and update these assets, given changes in international infrastructure and other impacts.

Description: Management guidelines were created to screen and manage asymptomatic renal stones in U.S. astronauts. The true risk for renal stone formation in astronauts due to the space flight environment is unknown. Proper management of this condition is crucial to mitigate health and mission risks. The NASA Flight Medicine Clinic electronic medical record and the Lifetime Surveillance of Astronaut Health databases were reviewed. An extensive review of the literature and current aeromedical standards for the monitoring and management of renal stones was also done. This work was used to develop a screening and management protocol for renal stones in astronauts that is relevant to the spaceflight operational environment. In the proposed guidelines all astronauts receive a yearly screening and post-flight renal ultrasound using a novel ultrasound protocol. The ultrasound protocol uses a combination of factors, including: size, position, shadow, twinkle and dispersion properties to confirm the presence of a renal calcification. For mission-assigned astronauts, any positive ultrasound study is followed by a low-dose renal computed tomography scan and urologic consult. Other specific guidelines were also created. A small asymptomatic renal stone within the renal collecting system may become symptomatic at any time, and therefore affect launch and flight schedules, or cause incapacitation during a mission. Astronauts in need of definitive care can be evacuated from the International Space Station, but for deep space missions evacuation is impossible. The new screening and management algorithm has been implemented and the initial round of screening ultrasounds is under way. Data from these exams will better define the incidence of renal stones in U.S. astronauts, and will be used to inform risk mitigation for both short and long duration spaceflights.

Description: The neural correlates of spaceflight-induced sensorimotor impairments are unknown. Head down-tilt bed rest (HDBR) serves as a microgravity analog because it mimics the headward fluid shift and limb unloading of spaceflight. We investigated focal brain white matter (WM) changes and fluid shifts during 70 days of 6 deg HDBR in 16 subjects who were assessed pre (2x), during (3x), and post-HDBR (2x). Changes over time were compared to those in control subjects (n=12) assessed four times over 90 days. Diffusion MRI was used to assess WM microstructure and fluid shifts. Free-Water Imaging, derived from diffusion MRI, was used to quantify the distribution of intracranial extracellular free water (FW). Additionally, we tested whether WM and FW changes correlated with changes in functional mobility and balance measures. HDBR resulted in FW increases in fronto-temporal regions and decreases in posterior-parietal regions that largely recovered by two weeks post-HDBR. WM microstructure was unaffected by HDBR. FW decreased in the post-central gyrus and precuneus. We previously reported that gray matter increases in these regions were associated with less HDBR-induced balance impairment, suggesting adaptive structural neuroplasticity. Future studies are warranted to determine causality and underlying mechanisms.

Description: PURPOSE: Exploration space missions pose several challenges to providing a comprehensive medication formulary designed to accommodate the size and space limitations of the spacecraft; while addressing the individual medications needs and preferences of the Crew; the negative outcome of a degrading inventory over time, the inability to resupply before expiration dates; and the need to properly forecast the best possible medication candidates to treat conditions that will occur in the future. METHODS: The Pharmacotherapeutics Discipline has partnered with the Exploration Medical Capabilities (ExMC) Element to develop and propose a research pathway that is comprehensively focused on evidence-based models and theories, as well as on new diagnostic tools and treatments or preventive measures aimed at closure of the Med02 Pharmacy Gap; defined in the Human Research Programs (HRP) risk-based research strategy. The Med02 Gap promotes the challenge to identify a strategy to ensure that medications used to treat medical conditions during exploration space missions are available, safe, and effective. It is abundantly clear that pharmaceutical intervention is an essential component of risk management planning for astronaut healthcare during exploration space. However, the quandary still remains of how to assemble a formulary that is comprehensive enough to prevent or treat anticipated medical events; and is also chemically stable, safe, and robust enough to have sufficient potency to last for the duration of an exploration space mission. In cases where that is not possible, addressing this Gap requires exploration of novel drug development techniques, dosage forms, and dosage delivery platforms that enhance chemical stability as well as therapeutic effectiveness. RESULTS: The proposed research pathway outlines the steps, processes, procedures, and a research portfolio aimed at identifying a capability that will provide a safe and effective pharmacy for any specific exploration Design Reference Mission (DRM). The proposed approach to building this research portfolio is to seek research projects that concentrate on four major focus areas; (1) Formulary selection, (2) Formulary potency and shelf life, (3) Formulary safety and toxicity, and (4) Novel technology and innovation such as portable real-time chemical analysis innovative drug therapies and dosage and delivery platforms. CONCLUSION: The research pathway has been completed and presented to the HRP. In spring 2017, it is scheduled to be reviewed by a panel of pharmaceutical and clinical experts that will evaluate the scientific merit and operational feasibility of the research pathway, as well as make suggestions for any warranted additions or improvements. Once finalized, the ExMC Element will proceed with the execution of this research pathway with the goal of gathering as much data, and learning as much as possible, to provide a safe and effective pharmaceutical formulary for use during exploration missions.

Description: INTRODUCTION: Among otherwise healthy astronauts undertaking deep space missions, the risks for acute appendicitis (AA) and cholecystitis (AC) are not zero. If these conditions were to occur during spaceflight they may require surgery for definitive care. The proposed study quantifies and compares the risks of developing de novo AA and AC in-flight to the surgical risks of prophylactic laparoscopic appendectomy (LA) and cholecystectomy (LC) using NASA's Integrated Medical Model (IMM). METHODS: The IMM is a Monte Carlo simulation that forecasts medical events during spaceflight missions and estimates the impact of these medical events on crew health. In this study, four Design Reference Missions (DRMs) were created to assess the probability of an astronaut developing in-flight small-bowel obstruction (SBO) following prophylactic 1) LA, 2) LC, 3) LA and LC, or 4) neither surgery (SR# S-20160407-351). Model inputs were drawn from a large, population-based 2011 Swedish study that examined the incidence and risks of post-operative SBO over a 5-year follow-up period. The study group included 1,152 patients who underwent LA, and 16,371 who underwent LC. RESULTS: Preliminary results indicate that prophylactic LA may yield higher mission risks than the control DRM. Complete analyses are pending and will be subsequently available. DISCUSSION: The risk versus benefits of prophylactic surgery in astronauts to decrease the probability of acute surgical events during spaceflight has only been qualitatively examined in prior studies. Within the assumptions and limitations of the IMM, this work provides the first quantitative guidance that has previously been lacking to this important question for future deep space exploration missions.

Description: Background: Carotid Intima Media Thickness (CIMT) has been demonstrated to be predictive of future cardiovascular events. Within various populations, radiation exposure, stress, and physical confinement have all been linked to an increased CIMT. Recent research discovered CIMT was significantly increased in ten long duration astronauts from pre-flight to four days post flight. The relationship between spaceflight and CIMT is not understood and trends in CIMT within the larger astronaut population are unknown. Methods: In 2010, CIMT was offered as part of the astronaut annual exam at the JSC Flight Medicine Clinic using a standardized CIMT screening protocol and professional sonographers. Between 2010 and 2016, CIMT measurements were collected on 213 NASA astronauts and payload specialists. The values used in this retrospective chart review are the mean of the CIMT from the right and left. Spaceflight exposure was categorized based on the total number of days spent in space at the time of the ground-based ultrasound (0, 1-29, 30-100, 101-200, 200). Linear regression with generalized estimating equations were used to estimate the association between spaceflight exposures and CIMT. Results: 530 studies were completed among 213 astronauts with a mean of 2.5 studies (range 1-6) per astronaut over the six year period. As in other populations, CIMT was significantly associated with age; however, gender was not. While there was no significant direct correlation between total spaceflight exposure and CIMT found, astronauts with 30-100 spaceflight days and astronauts with greater than 100 spaceflight days had significantly increased CIMT over astronauts who had never flown (p=0.002 and p=〈0.0001 respectively) after adjustment for age. Conclusion: Further work is needed to fully understand CIMT and its association to spaceflight. Current occupational surveillance activities are under way to study CIMT values in conjunction with other cardiovascular risk factors among astronauts as compared to the general population.

Description: Introduction. This joint European Space Agency/NASA pre- and post-flight study investigates the influence of exposure to microgravity on the subjective straight ahead (SSA) in crewmembers returning from long-duration expeditions to the International Space Station (ISS). The SSA is a measure of the internal representation of body orientation and to be influenced by stimulation of sensory systems involved in postural control. The use of a vibrotactile sensory aid to correct the representation of body tilted relative to gravity is also tested as a countermeasure. This study addresses the sensorimotor research gap to "determine the changes in sensorimotor function over the course of a mission and during recovery after landing." Research Plans. The ISS study will involve eight crewmembers who will participate in three pre-flight sessions (between 120 and 60 days before launch) and then three post-flight sessions on R plus 0/1 day, R plus 4 days, and R plus 8 days. Sixteen control subjects were also tested during three sessions to evaluate the effects of repeated testing and to establish normative values. The experimental protocol includes measurements of gaze and arm movements during the following tasks: (1) Near & Far Fixation: The subject is asked to look at actual targets in the true straight-ahead direction or to imagine these targets in the dark. Targets are located at near distance (arm's length) and far distance (beyond 2 meters). This task is successively performed with the subject's body aligned with the gravitational vertical, and with the subject's body tilted in pitch relative to the gravitational vertical using a tilt chair. Measures are then compared with and without a vibrotactile sensory aid that indicates how far one has tilted relative to the vertical; (2) Eye and Arm Movements: The subject is asked to look and point in the SSA direction in darkness and then make horizontal and vertical eye or arm movements, relative to Earth coordinates (allocentric) and to the subject's head/body reference (egocentric). This task is successively performed with the subject's body aligned with the gravitational vertical, and with subject's body tilted in roll using a tilt chair; (3) Linear Vestibulo-Ocular Reflex: The subject is asked to fixate actual visual targets at near and far distances in the true straight-ahead direction, and to evaluate the distance of these targets. The subject is asked to continue fixating the same imagined targets in darkness while he/she is passively accelerated up and down on a spring-loaded vertical linear accelerator. Results. In the control subject population, the perceived tilt angles, translations, and distances were remarkably close to the actual values. The pointing tasks indicated that the orientation of arm saccades was influenced by both the gravitational vertical and the body idiotropic vector. Repeating the testing did not reveal any significant changes. Preliminary results obtained in three crewmembers before and after flight will also be presented. Applications. A change in an individual's egocentric reference might have negative consequences on evaluating the direction of an approaching object or on the accuracy of reaching movements or locomotion. Consequently, investigating how microgravity affects the target location will have theoretical, operational, and even clinical implications for future space exploration missions. The use of vibrotactile feedback as a sensorimotor countermeasure is applicable to balance therapy applications for patients with vestibular loss and the elderly to mitigate risks due to loss of spatial orientation.

Description: Upon return from spaceflight, a majority of crewmembers experience motion sickness (MS) symptoms. The interactions between crewmembers' adaptation to a gravitational transition, the performance decrements resulting from MS and/or use of promethazine (PMZ), and the constraints imposed by mission task demands could significantly challenge and limit an astronaut's ability to perform functional tasks during gravitational transitions. No operational countermeasure currently exists to mitigate the risks associated with these sensorimotor disturbances. Stochastic resonance (SR) can be thought of simply as "noise benefit" or an increase in information transfer by a system when in the presence of a non-zero level of noise. We have shown that low levels of stochastic vestibular stimulation (SVS) improve balance and locomotor performance due to SR (Goel et al. 2015, Mulavara et al. 2011, 2015). Additionally, a study in a 6-hydroxydopamine (6-OHDA) hemi-lesioned rat model of Parkinson's disease demonstrated improvements in locomotor activity after low-level SVS delivery possibly due to an increase in nigral gamma-aminobutyric acid (GABA) release in a dopamine independent way (Samoudi et al. 2012). SVS specifically increased GABA release on the lesioned, but not the intact side. These results suggest that SVS can cause targeted alterations of GABA release to affect performance of functional tasks. Activation of the GABA pathway is important in modulating MS and promoting adaptability (Cohen 2008). Magnusson et al. (2000) supported this finding by showing that the administration of a GABAB agonist caused a reversal of the symptoms that is normally seen after unilateral labyrinthectomy. Thus, GABA could play a significant role in reducing MS and promoting adaptability. We have taken advantage of the SR mechanism as a modulator of neurotransmitters to develop a unique SVS countermeasure system to mitigate MS symptoms and improve functional performance after landing. Healthy subjects (n=20) participated in two test sessions, one in which they received +/-400 microA of SVS and one where they received no stimulation (0 microA); the study design was counterbalanced. Subjects began by performing a series of four functional tasks 3-5 times as baseline measurements of task performance. Then, to induce MS, subjects walked an obstacle course with up-down reversing prisms. If they completed the course before achieving our pre-determined level of MS, they were asked to read a poster while making large up-down head movements to a metronome while still wearing the reversing prism goggles. Subjects were stopped every two minutes and asked to report their MS symptoms. Using the Pensacola Scale for motion sickness, test operators evaluated the level of MS of each subject. Once a subject reached an 8 on this scale, which is equivalent to mild malaise, or 30 minutes had passed since the start of the MS induction, this protocol was stopped. Finally, immediately after MS induction, subjects were asked to complete the four functional tasks again. Although, 100% of our subjects experienced at least one MS symptom, only 55% of our subjects experienced stomach awareness to any degree. Without SVS, only 40% of subjects lasted the full 30-minute MS induction protocol, while 65% of subjects lasted the full 30 minutes with SVS, which is nearly a significant increase (p=0.056). In addition, subjects showed significant improvement from baseline when performing a tandem walk and a prone-to-stand test immediately after the MS induction protocol was stopped but the stimulation level was continued. The results are promising and future work includes comparing MS progression between PMZ and SVS directly in subjects that are provoked to a minimum of nausea. Low levels of SVS stimulation may serve as a non-pharmacological countermeasure to replace or reduce the PMZ dosage requirements and concurrently improve functional performance during transitions to new gravitational environments after spaceflight.

Description: Introduction. NASA's Human Research Program is focused on addressing health risks associated with long-duration missions on the International Space Station (ISS) and future exploration-class missions beyond low Earth orbit. Visual acuity changes observed after short-duration missions were largely transient, but now more than 50 percent of ISS astronauts have experienced more profound, chronic changes with objective structural findings such as optic disc edema, globe flattening and choroidal folds. These structural and functional changes are referred to as the visual impairment and intracranial pressure (VIIP) syndrome. Development of VIIP symptoms may be related to elevated intracranial pressure (ICP) secondary to spaceflight-induced cephalad fluid shifts, but this hypothesis has not been tested. The purpose of this study is to characterize fluid distribution and compartmentalization associated with long-duration spaceflight and to determine if a relation exists with vision changes and other elements of the VIIP syndrome. We also seek to determine whether the magnitude of fluid shifts during spaceflight, as well as any VIIP-related effects of those shifts, are predicted by the crewmember's pre-flight status and responses to acute hemodynamic manipulations, specifically posture changes and lower body negative pressure. Methods. We will examine a variety of physiologic variables in 10 long-duration ISS crewmembers using the test conditions and timeline presented in the figure below. Measures include: (1) fluid compartmentalization (total body water by D2O, extracellular fluid by NaBr, intracellular fluid by calculation, plasma volume by CO rebreathe, interstitial fluid by calculation); (2) forehead/eyelids, tibia, and calcaneus tissue thickness (by ultrasound); (3) vascular dimensions by ultrasound (jugular veins, cerebral and carotid arteries, vertebral arteries and veins, portal vein); (4) vascular dynamics by MRI (head/neck blood flow, cerebrospinal fluid pulsatility); (5) ocular measures (optical coherence tomography; intraocular pressure; 2-dimensional ultrasound including optic nerve sheath diameter, globe flattening, and retina-choroid thickness; Doppler ultrasound of ophthalmic and retinal arteries and veins); (6) cardiac variables by ultrasound (inferior vena cava, tricuspid flow and tissue Doppler, pulmonic valve, stroke volume, right heart dimensions and function, four-chamber views); and (7) ICP measures (tympanic membrane displacement, otoacoustic emissions). Pre- and post-flight, acute head-down tilt will induce cephalad fluid shifts, whereas lower body negative pressure will oppose these shifts. Controlled Mueller maneuvers will manipulate cardiovascular variables. Through interventions applied before, during, and after flight, we intend to fully evaluate the relationship between fluid shifts and the VIIP syndrome. Discussion. Ten subjects have consented to participate in this experiment, including the recent One-Year Mission crewmembers, who have recently completed R plus180 testing; all other subjects have completed pre-flight testing. Preliminary results from the One-Year Mission crewmembers will be presented, including measures of ocular structure and function, vascular dimensions, fluid distribution, and non-invasive estimates of intracranial pressure.

Description: Given that spaceflight may induce adverse changes in bone ultimate strength with respect to mechanical loads during and post-mission, there is a possibility a fracture may occur for activities otherwise unlikely to induce fracture prior to initiating spaceflight.

Description: No abstract available

Description: As spaceflight durations have increased over the last four decades, the effects of weightlessness on the human body are far better understood, as are the countermeasures. A combination of aerobic and resistive exercise devices contribute to countering the losses in muscle strength, aerobic fitness, and bone strength of today's astronauts and cosmonauts that occur during their missions on the International Space Station. Creation of these systems has been a dynamically educational experience for designers and engineers. The ropes and cables in particular have experienced a wide range of challenges, providing a full set of lessons learned that have already enabled improvements in on-orbit reliability by initiating system design improvements. This paper examines the on-orbit experience of ropes and cables in several exercise devices and discusses the lessons learned from these hardware items, with the goal of informing future system design.

Description: NASA has identified a potential risk of spatial disorientation to future astronauts during re-entry of the proposed Orion spacecraft. The purpose of this study was to determine if a 6-hour physiological training procedure, Autogenic-Feedback Training Exercise (AFTE), can mitigate these effects. Twenty subjects were assigned to two groups (AFTE and Control) matched for motion sickness susceptibility and gender. All subjects received a standard rotating chair test to determine motion sickness susceptibility; three training sessions on a manual performance task; and four exposures to a simulated Orion re-entry test in the rotating chair. Treatment subjects were given two hours of AFTE training before each Orion test. A diagnostic scale was used to evaluate motion sickness symptom severity. Results showed that 2 hours of AFTE significantly reduced motion sickness symptoms during the second Orion test. AFTE subjects were able to maintain lower heart rates and skin conductance levels and other responses than the control group subjects during subsequent tests. Trends show that performance was less degraded for AFTE subjects. The results of this study indicate that astronauts could benefit from receiving at least 2 hours of preflight AFTE. In addition, flight crews could benefit further by practicing physiologic self-regulation using mobile devices.

Description: No abstract available

Description: The present invention includes compositions and methods for the use of an encapsulation additive having between about 0.1 to about 30 percent isolated and purified vitelline protein B to provide for mixed and extended release formulations.

Description: NASA has concerns regarding the incidence and clinical significance of cardiac arrhythmias that could occur during long-term exposure to the spaceflight environment, such as on the International Space Station (ISS) or during a prolonged (e.g., up to 3 years) sojourn to Mars or on the Moon. There have been some anecdotal reports and a few documented cases of cardiac arrhythmias in space, including one documented episode of non-sustained ventricular tachycardia. The potential catastrophic nature of a sudden cardiac death in the remote space environment has led to concerns from the early days of the space program that spaceflight might be arrhythmogenic. Indeed, there are known and well-defined changes in the cardiovascular system with spaceflight: a) plasma volume is reduced, b) left ventricular mass is decreased, and c) the autonomic nervous system adapts to the weightless environment. Combined, these physiologic adaptations suggest that changes in cardiac structure and neuro-humoral environment during spaceflight could alter electrical conduction, although the evidence supporting this contention consists mostly of minor changes in QT interval (the time between the start of the Q wave and the end of the T wave on an electrocardiogram tracing) in a small number of astronauts after long-duration spaceflight. Concurrent with efforts by NASA Medical Operations to refine and improve screening techniques relevant to arrhythmias and cardiovascular disease, as NASA enters the era of exploration-class missions it will be critical to determine with the highest degree of certainty whether spaceflight by itself alters cardiac structure and function sufficiently to increase the risk of arrhythmias.

Description: A subset of astronauts develop neuro-ocular structural and functional changes during prolonged periods of spaceflight that may lead to additional neurologic and ocular consequences upon return to Earth.

Description: NASA medical care standards establish requirements for providing health and medical programs for crewmembers during all phases of a mission. These requirements are intended to prevent or mitigate negative health consequences of long-duration spaceflight, thereby optimizing crew health and performance over the course of the mission. Current standards are documented in the two volumes of the NASA-STD-3001 Space Flight Human-System Standard document, established by the Office of the Chief Health and Medical Officer. Its purpose is to provide uniform technical standards for the design, selection, and application of medical hardware, software, processes, procedures, practices, and methods for human-rated systems. NASA-STD-3001 Vol. 1 identifies five levels of care for human spaceflight. These levels of care are accompanied by several components that illustrate the type of medical care expected for each. The Exploration Medical Capability (ExMC) of the Human Research Program has expanded the context of these provided levels of care and components. This supplemental information includes definitions for each component of care and example actions that describe the type of capabilities that coincide with the definition. This interpretation is necessary in order to fully and systematically define the capabilities required for each level of care in order to define the medical requirements and plan for infrastructure needed for medical systems of future exploration missions, such as one to Mars.

Description: Ultrasound (US) specifically looking for asymptomatic renal calcifications that may be renal stones is typically not done in the terrestrial setting. Standard abdominal US without a renal focus may discover incidental, mineralized renal material (MRM); however punctate solid areas of MRM is less than 3 mm are usually considered subclinical. Detecting these early calcifications before they become symptomatic renal stones is critical to prevent adverse medical and mission outcomes during spaceflight.

Description: While Ocular Coherence Tomography (OCT) is not a first-line modality to evaluate anterior eye structures terrestrially, it is a resource already available on the International Space Station (ISS) that can be used in medical contingencies that involve the anterior eye. With remote guidance and subject matter expert (SME) support from the ground, a minimally trained crewmember can now use OCT to evaluate anterior eye pathologies on orbit. OCT utilizes low-coherence interferometry to produce detailed cross-sectional and 3D images of the eye in real time. Terrestrially, it has been used to evaluate macular pathologies and glaucoma. Since 2013, OCT has been used onboard the ISS as one part of a suite of hardware to evaluate the Visual Impairment/Intracranial Pressure risk faced by astronauts, specifically assessing changes in the retina and choroid during space flight. The Anterior Segment Module (ASM), an add-on lens, was also flown for research studies, providing an opportunity to evaluate the anterior eye in real time if clinically indicated. Anterior eye pathologies that could be evaluated using OCT were identified. These included corneal abrasions and ulcers, scleritis, and acute angle closure glaucoma. A remote guider script was written to provide ground specialists with step-by-step instructions to guide ISS crewmembers, who do not get trained on the ASM, to evaluate the anterior eye. The instructions were tested on novice subjects and/or operators, whose feedback was incorporated iteratively. The final remote guider script was reviewed by SME optometrists and NASA flight surgeons. The novel application of OCT technology to space flight allows for the acquisition of objective data to diagnose anterior eye pathologies when other modalities are not available. This demonstrates the versatility of OCT and highlights the advantages of using existing hardware and remote guidance skills to expand clinical capabilities in space flight.

Description: Long duration spaceflight has a negative effect on the human body, and exercise countermeasures are used on-board the International Space Station (ISS) to minimize bone and muscle loss, combatting these effects. Given the importance of these hardware systems to the health of the crew, this equipment must continue to be readily available. Designing spaceflight exercise hardware to meet high reliability and availability standards has proven to be challenging throughout the time the crewmembers have been living on ISS beginning in 2000. Furthermore, restoring operational capability after a failure is clearly time-critical, but can be problematic given the challenges of troubleshooting the problem from 220 miles away. Several best-practices have been leveraged in seeking to maximize availability of these exercise systems, including designing for robustness, implementing diagnostic instrumentation, relying on user feedback, and providing ample maintenance and sparing. These factors have enhanced the reliability of hardware systems, and therefore have contributed to keeping the crewmembers healthy upon return to Earth. This paper will review the failure history for three spaceflight exercise countermeasure systems identifying lessons learned that can help improve future systems. Specifically, the Treadmill with Vibration Isolation and Stabilization System (TVIS), Cycle Ergometer with Vibration Isolation and Stabilization System (CEVIS), and the Advanced Resistive Exercise Device (ARED) will be reviewed, analyzed, and conclusions identified so as to provide guidance for improving future exercise hardware designs. These lessons learned, paired with thorough testing, offer a path towards reduced system down-time.

Description: Radiation induced cancer risks are driven by genetic instability. It is not well understood how different radiation sources induce genetic instability in cells with different genetic background. Here we report our studies on genetic instability, particularly chromosome instability using fluorescence in situ hybridization (FISH), in human primary lymphocytes, normal human fibroblasts, and transformed human mammary epithelial cells in a temporal manner after exposure to high energy protons and Fe ions. The chromosome spread was prepared 48 hours, 1 week, 2 week, and 1 month after radiation exposure. Chromosome aberrations were analyzed with whole chromosome specific probes (chr. 3 and chr. 6). After exposure to protons and Fe ions of similar cumulative energy (??), Fe ions induced more chromosomal aberrations at early time point (48 hours) in all three types of cells. Over time (after 1 month), more chromosome aberrations were observed in cells exposed to Fe ions than in the same type of cells exposed to protons. While the mammary epithelial cells have higher intrinsic genetic instability and higher rate of initial chromosome aberrations than the fibroblasts, the fibroblasts retained more chromosomal aberration after long term cell culture (1 month) in comparison to their initial frequency of chromosome aberration. In lymphocytes, the chromosome aberration frequency at 1 month after exposure to Fe ions was close to unexposed background, and the chromosome aberration frequency at 1 month after exposure to proton was much higher. In addition to human cells, mouse bone marrow cells isolated from strains CBA/CaH and C57BL/6 were irradiated with proton or Fe ions and were analyzed for chromosome aberration at different time points. Cells from CBA mice showed similar frequency of chromosome aberration at early and late time points, while cells from C57 mice showed very different chromosome aberration rate at early and late time points. Our results suggest that relative biological effectiveness (RBE) of radiation are different for different radiation sources, for different cell types, and for the same cell type with different genetic background at different times after radiation exposure. Caution must be taken in using RBE value to estimate biological effects from radiation exposure.

Description: Introduction: Microgravity exposure may alter the likelihood that astronauts will experience renal stones. The potential risk includes both acute and chronic health issues, with the potential for significant impact on mission objectives. Methods: To understand the role of the NASA's Human Research Program (HRP) research agenda in both preventing and addressing renal stones in spaceflight, current astronaut epidemiologic data and a summary of programmatic considerations are reviewed. Results: Although there has never been a symptomatic renal stone event in a U.S. crewmember during spaceflight, urine chemistry has been altered - likely due to induced changes in renal physiology as a result of exposure to microgravity. This may predispose astronauts to stone formation, leading the HRP to conduct and sponsor research to: 1) understand the risk of stone formation in space; 2) prevent stones from forming; and 3) address stones that may form by providing novel diagnostic and therapeutic approaches. Discussion: The development of a renal stone during spaceflight is a significant medical concern that requires the HRP to minimize this risk by providing the ability to prevent, diagnose, monitor and treat the condition during spaceflight. A discussion of the risk as NASA understands it is followed by an overview of the multiple mitigations currently under study, including novel ultrasound techniques for stone detection and manipulation, and how they may function as part of a larger exploration medical system.

Description: The Exploration Medical Capability (ExMC) Element systems engineering goals include defining the technical system needed to implement exploration medical capabilities for Mars. This past year, scenarios captured in the medical system concept of operations laid the foundation for systems engineering technical development work. The systems engineering team analyzed scenario content to identify interactions between the medical system, crewmembers, the exploration vehicle, and the ground system. This enabled the definition of functions the medical system must provide and interfaces to crewmembers and other systems. These analyses additionally lead to the development of a conceptual medical system architecture. The work supports the ExMC community-wide understanding of the functional exploration needs to be met by the medical system, the subsequent development of medical system requirements, and the system verification and validation approach utilizing terrestrial analogs and precursor exploration missions.

Description: Medical support of spaceflight training operations across international lines is a unique circumstance with potential applications to other aerospace medicine support scenarios. KBRwyle's Star City Medical Support Group (SCMSG) has fulfilled this role since the Mir-Shuttle era, with extensive experience and updates to share with the greater AsMA community. OVERVIEW: The current Soyuz training flow for assigned ISS crewmembers takes place in Star City, Russia. Soyuz training flow involves numerous activities that pose potential physical and occupational risks to crewmembers, including centrifuge runs and pressurized suit simulations at ambient and hypobaric pressures. In addition, Star City is a relatively remote location in a host nation with variable access to reliable, Western-standard medical care. For these reasons, NASA's Human Health & Performance contract allocates full-time physician support to assigned ISS crewmembers training in Star City. The Star City physician also treats minor injuries and illnesses as needed for both long- and short-term NASA support personnel traveling in the area, while working to develop and maintain relationships with local health care resources in the event of more serious medical issues that cannot be treated on-site. The specifics of this unique scope of practice will be discussed. SIGNIFICANCE: ISS crewmembers training in Star City are at potential physical and occupational risk of trauma or dysbarism during nominal Soyuz training flow, requiring medical support from an on-duty aerospace medicine specialist. This support maintains human health and performance by preserving crewmember safety and well-being for mission success; sharing information regarding this operational model may contribute to advances in other areas of international, military, and civilian operational aerospace medicine.

Description: INTRODUCTION: NASA's Space Medicine community knowledge regarding the "Vision Impairment Intracranial Pressure", or VIIP.has been evolving over time.. Various measures of occupational health related to this condition had to be determined and then plans/processes put into place. The most robust of these processes were inititated in 2010. This presentation will provide a clinic update of the astronaut occupational health data related to VIIP. METHODS: NASA and its international partners require its astronauts to undergo routine health measures deemed important to monitoring VIIP. The concern is that the spaceflight environment aboard ISS could cause some astronauts to have physiologic changes detrimental to either ongoing mission operations or long-term health related to the ocular system and possibly the CNS. Specific medical tests include but are not limited to brain/orbit MRI (NASA unique protocol), OCT, fundoscopy and ocular ultrasound. Measures are taken prior to spaceflight, in-flight and post-flight. Measures to be reported include incidence of disc edema, globe flattening, choroidal folds, ONSD and change in refractive error. RESULTS: 73 ISS astronauts have been evaluated at least partially for VIIP related measures. Of these individuals, approximately 1 in 7 have experienced disc edema. The prevalence of the other findings is more complicated as the medical testing has changed over time. Overall, 26 separate individuals have experienced at least one of the findings NASA has associated with VIIP Another confounding factor is most of the astronauts have prior spaceflight experience at the time of the "pre-flight" testing. DISCUSSION: In 2010 NASA and its US operating segment (USOS) partners (CSA, ESA and JAXA) began routine occupational monitoring and data collection for most VIIP related changes. Interpretation of that data is extremely challenging for several reasons. For example, the determination of disc edema is the most complete finding as we have had highly qualified optometrists routinely and competently performing post-flight funduscopic exams for the entirety of the ISS program. Yet in 2013 NASA added OCT to our in-flight suite of eye exams. Shortly after routine screening with the OCT, a new term appeared within VIIP vernacular - "subclinical disc edema". OCT has much greater ability to measure change within the retina and provides significantly more data to analyze, understand and communicate out. Communicating VIIP data clearly adds even more challenge. Historically we've reported data per eye and not necessarily per person. This has led to difficulty in understanding how many individuals have experienced "VIIP" within the aerospace medicine community. The presenter will attempt to provide clear and concise communication of VIIP findings.

Description: It is known that spaceflight adversely affects human sensorimotor function. With interests in longer duration deep space missions it is important to understand microgravity dose-response relationships. NASA's One Year Mission project allows for comparison of the effects of one year in space with those seen in more typical six month missions to the International Space Station. In the Neuromapping project we are performing structural and functional magnetic resonance brain imaging to identify the relationships between changes in neurocognitive function and neural structural alterations following a six month International Space Station mission. Our central hypothesis is that measures of brain structure, function, and network integrity will change from pre- to post-spaceflight. Moreover, we predict that these changes will correlate with indices of cognitive, sensory, and motor function in a neuroanatomically selective fashion. Our interdisciplinary approach utilizes cutting edge neuroimaging techniques and a broad-ranging battery of sensory, motor, and cognitive assessments that are conducted pre-flight, during flight, and post-flight to investigate potential neuroplastic and maladaptive brain changes in crewmembers following long-duration spaceflight. With the one year mission we had one crewmember participate in all of the same measures pre-, per- and post-flight as in our ongoing study. During this presentation we will provide an overview of the magnitude of changes observed with our brain and behavioral assessments for the one year crewmember in comparison to participants that have completed our six month study to date.

Description: Astronauts and cosmonauts may experience symptoms of orthostatic intolerance during re-entry, landing, and for several days post-landing following short- and long-duration spaceflight. Presyncopal symptoms have been documented in approximately 20% of short-duration and greater than 60% of long-duration flyers on landing day specifically during 5-10 min of controlled (no countermeasures employed at the time of testing) stand tests or 80 deg head-up tilt tests. Current operational countermeasures to orthostatic intolerance include fluid loading prior to and whole body cooling during re-entry as well as compression garments that are worn during and for up to several days after landing. While both NASA and the Russian space program have utilized compression garments to protect astronauts and cosmonauts traveling on their respective vehicles, a "next-generation" gradient compression garment (GCG) has been developed and tested in collaboration with a commercial partner to support future space flight missions. Unlike previous compression garments used operationally by NASA that provide a single level of compression across only the calves, thighs, and lower abdomen, the GCG provides continuous coverage from the feet to below the pectoral muscles in a gradient fashion (from approximately 55 mm Hg at the feet to approximately 16 mmHg across the abdomen). The efficacy of the GCG has been demonstrated previously after a 14-d bed rest study without other countermeasures and after short-duration Space Shuttle missions. Currently the GCG is being tested during a stand test following long-duration missions (~6 months) to the International Space Station. While results to date have been promising, interactions of the GCG with other space suit components have not been examined. Specifically, it is unknown whether wearing the GCG over NASA's Maximum Absorbency Garment (MAG; absorbent briefs worn for the collection of urine and feces while suited during re-entry and landing) will interfere with the effectiveness of the GCG or conversely whether the GCG will reduce the fluid absorption capabilities of the MAG. Methods: This operational, directed study, will (1) determine whether the effectiveness of the GCG is affected by the MAG with regard to cardiovascular responses to head-up tilt, the standard orthostatic intolerance test employed for astronauts and bed rest subjects; (2) determine whether the effectiveness of the MAG is compromised by the GCG tested by injecting a standard fluid volume (950 ml in 3 separate simulated "urine voids") at a standardized rate (30 ml/sec); and (3) determine whether comfort is affected by wearing the MAG under the GCG using a standardized questionnaire. Results from this study will guide future development and operational use of the GCG and MAG to maximize crew health, safety, and comfort.

Description: Damaging effects due to spaceflight and long-duration weightlessness are seen in the musculoskeletal system, specifically with regards to bone loss, bone resorption, and changes in overall bone structure. These adverse effects are all seen with indicators of oxidative stress and a variation in the levels of oxidative gene expression. Once gravity is restored, however, the recovery is slow and incomplete. Despite this, few reports have investigated the correlation between oxidative damage and general modifications within the bone. In this project, we will make use of a ground-based model of simulated weightlessness (hindlimb unloading, HU) in order to observe skeletal changes in response to induced microgravity due to changes in oxidative pressures. With this model we will analyze samples at 14-day and 90-day time points following HU for the determination of acute and chronic effects, each with corresponding controls. We hypothesize that simulated microgravity will lead to skeletal adaptations including time-dependent activation of pro-oxidative processes and pro-osteoclastogenic signals related to the progression, plateau, and recovery of the bone. Microcomputed tomography techniques will be utilized to measure skeletal changes in response to HU. With the results of this study, we hope to further the understanding of skeletal affects as a result of long-duration weightlessness and develop countermeasures to combat bone loss in spaceflight and osteoporosis on Earth.

Description: Human exploration missions that reach destinations beyond low Earth orbit, such as Mars, will present significant new challenges to crew health management. For the medical system, lack of consumable resupply, evacuation opportunities, and real-time ground support are key drivers toward greater autonomy. Recognition of the limited mission and vehicle resources available to carry out exploration missions motivates the Exploration Medical Capability (ExMC) Element's approach to enabling the necessary autonomy. The Element's work must integrate with the overall exploration mission and vehicle design efforts to successfully provide exploration medical capabilities. ExMC is applying systems engineering principles and practices to accomplish its goals. This paper discusses the structured and integrative approach that is guiding the medical system technical development. Assumptions for the required levels of care on exploration missions, medical system goals, and a Concept of Operations are early products that capture and clarify stakeholder expectations. Model-Based Systems Engineering techniques are then applied to define medical system behavior and architecture. Interfaces to other flight and ground systems, and within the medical system are identified and defined. Initial requirements and traceability are established, which sets the stage for identification of future technology development needs. An early approach for verification and validation, taking advantage of terrestrial and near-Earth exploration system analogs, is also defined to further guide system planning and development.

Description: Biological risks associated with microgravity is a major concern for space travel. Although determination of risk has been a focus for NASA research, data examining systemic (i.e., multi- or pan-tissue) responses to space flight are sparse. The overall goal of our work is to identify potential master regulators responsible for such responses to microgravity conditions. To do this we utilized the NASA GeneLab database which contains a wide array of omics experiments, including data from: 1) different flight conditions (space shuttle (STS) missions vs. International Space Station (ISS); 2) different tissues; and 3) different types of assays that measure epigenetic, transcriptional, and protein expression changes. We have performed meta-analysis identifying potential master regulators involved with systemic responses to microgravity. The analysis used 7 different murine and rat data sets, examining the following tissues: liver, kidney, adrenal gland, thymus, mammary gland, skin, and skeletal muscle (soleus, extensor digitorum longus, tibialis anterior, quadriceps, and gastrocnemius). Using a systems biology approach, we were able to determine that p53 and immune related pathways appear central to pan-tissue microgravity responses. Evidence for a universal response in the form of consistency of change across tissues in regulatory pathways was observed in both STS and ISS experiments with varying durations; while degree of change in expression of these master regulators varied across species and strain, some change in these master regulators was universally observed. Interestingly, certain skeletal muscle (gastrocnemius and soleus) show an overall down-regulation in these genes, while in other types (extensor digitorum longus, tibialis anterior and quadriceps) they are up-regulated, suggesting certain muscle tissues may be compensating for atrophy responses caused by microgravity. Studying these organtissue-specific perturbations in molecular signaling networks, we demonstrate the value of GeneLab in characterizing potential master regulators associated with biological risks for spaceflight.

Description: A review will be presented on the progress made under STMDGame Changing Development Program Funding towards the development of a Medical Decision Support System for augmenting crew capabilities during long-duration missions, such as Mars Transit. To create an MDSS, initial work requires acquiring images and developing models that analyze and assess the features in such medical biosensor images that support medical assessment of pathologies. For FY17, the project has focused on ultrasound images towards cardiac pathologies: namely, evaluation and assessment of pericardial effusion identification and discrimination from related pneumothorax and even bladder-induced infections that cause inflammation around the heart. This identification is substantially changed due to uncertainty due to conditions of fluid behavior under space-microgravity. This talk will present and discuss the work-to-date in this Project, recognizing conditions under which various machine learning technologies, deep-learning via convolutional neural nets, and statistical learning methods for feature identification and classification can be employed and conditioned to graphical format in preparation for attachment to an inference engine that eventually creates decision support recommendations to remote crew in a triage setting.

Description: Understanding the effects of spaceflight on mammalian reproductive and developmental physiology is important to future human space exploration and permanent settlement beyond Earth orbit. Fetal developmental programming, including modulation of the HPA axis, is thought to originate at the placental-uterine interface, where both transfer of maternal hormones to the fetus and synthesis of endogenous hormones occurs. In healthy rats, fetal corticosterone levels are kept significantly lower by 11BetaHSD-2, which inactivates corticosterone by conversion into cortisone. Placental tissues express endogenous HPA axis-associated hormones including corticotropin-releasing hormone (CRH), pre-opiomelanocortin (POMC), and vasopressin, which may contribute to fetal programming alongside maternal hormones. DNA methylase 3A, 11BetaHSD-2, and 11BetaHSD-1, which are involved in the regulation of maternal cortisol transfer and modulation of the HPA axis, are also expressed in placental tissues along with glucocorticoid receptor and may be affected by differential gravity exposure during pregnancy. Fetuses may respond differently to maternal glucocorticoid exposure during gestation through sexually dimorphic expression of corticosterone-modulating hormones. To elucidate effects of altered gravity on placental gene expression, here we present a ground-based analogue study involving continuous centrifugation to produce 2g hypergravity. We hypothesized that exposure to 2g would induce a decrease in 11BetaHSD-2 expression through the downregulation of DNA methylase 3a and GC receptor, along with concurrent upregulation in endogenous CRH, POMC, and vasopressin expression. Timed pregnant female rats were exposed to 2G from Gestational day 6 to Gestational day 20, and comparisons made with Stationary Control (SC) and Vivarium Control (VC) dams at 1G. Dams were euthanized and placentas harvested on G20. We homogenized placental tissues, extracted and purified RNA, synthesized cDNA, and quantified the expression levels of the genes of interest relative to the GAPDH housekeeping gene, using RT-qPCR and gene-specific cDNA probes. Elucidation of glucocorticoid transfer and synthesis in the placenta can provide new insights into the unique dynamics of mammalian development in microgravity and guide future multi-generational studies in space.

Description: No abstract available

Description: Upon atmospheric exitre-entry and during training, astronauts are subjected to temporary periods of hypergravity, which has been implicated in the activation of oxidative stress pathways contributing to mitochondrial dysfunction and neuronal degeneration. The pathogenesis of Parkinsons disease and other neurodegenerative disorders is associated with oxidative damage to neurons involved in dopamine systems of the brain. Our study aims to examine the effects of a hypergravitational developmental environment on the degeneration of dopaminergic systems in Drosophila melanogaster. Male and female flies (Gal4-UAS transgenic line) were hatched and raised to adulthood in centrifugal hypergravity (97rpm, 3g). The nuclear expression of the reporter, Green Fluorescent Protein (GFP) is driven by the dopaminergic enzyme tyrosine hydroxylase (TH) promoter, allowing for the targeted visualization of dopamine producing neurons. After being raised to adulthood and kept in hypergravity until 18 days of age, flies were dissected and the expression of TH was measured by fluorescence confocal microscopy. TH expression in the fly brains was used to obtain counts of healthy dopaminergic neurons for flies raised in chronic hypergravity and control groups. Dopaminergic neuron expression data were compared with those of previous studies that limited hypergravity exposure to late life in order to determine the flies adaptability to the gravitational environment when raised from hatching through adulthood. Overall, we observed a significant effect of chronic hypergravity exposure contributing to deficits in dopaminergic neuron expression (p 0.003). Flies raised in 3g had on average lower dopaminergic neuron counts (mean 97.7) when compared with flies raised in 1g (mean 122.8). We suspect these lower levels of TH expression are a result of oxidative dopaminergic cell loss in flies raised in hypergravity. In future studies, we hope to further elucidate the mechanism by which hypergravity-induced oxidative stress damages the dopaminergic neuronal system, as well as examining possible chemical countermeasures to the hypergravity-induced oxidative stress response in dopaminergic neurons in order to combat cell death and consequent mental and behavioral deficits.

Description: As NASA and other space agencies prepare for future long-term space missions beyond the LEO, the cumulative impact of risk factors encountered in space increases substantially rising concerns about astronauts health. Application of on-board medications to mitigate clinical symptoms associated with certain medical conditions and illnesses is the first line of response to ensure sustainable health and performance of crew. Unfortunately, very limited research has been conducted to determine efficacy of the earth-based pharmaceuticals in a microgravity environment. In some instances, orally administered medications taken during flight were reported to be less effective than expected. Evaluation of series of experiments involving astronauts from shuttle flights shows notable individual variability to several pharmaceuticals during flight. These data provide reasonable assumption of perturbation in CYP450 enzymes during spaceflight, which contribute to the hepatic metabolism of the majority of drugs and therefore may have significant effects on therapeutic efficacy and increase treatment-related toxicity. The genes encoding the CYP450 enzymes are highly variable in humans. Inheritable variations of CYP450 hepatic metabolizer enzymes and transport proteins play a crucial role in the inter-individual variability of drug efficiency and risks of adverse drug reactions. Additionally, there are some reports that document changes in the levels of production of drug-metabolizing enzymes in microgravity. Therefore, in order to provide a safe and effective pharmaceutical treatment in space, medications selection should be based not only on the specific efficacy of medications but also on the individual drug sensitivity and flight-induced changes in metabolism of astronauts chosen for a particular mission. To our knowledge, there was no pre-flight drug sensitivity testing on a genetic level for any of the previous manned NASA space missions. Therefore, technologies capable of predicting and managing medication efficacy, side effects, and toxicity of drugs based on individual genetic variability of crew members are increasingly needed. In this report, we present results of testing the market available Personalized Prescribing System (PPS), a comprehensive, non-invasive solution for safer, targeted medication management for every crew member. Statistical accuracy and simplicity of non-invasive sample analysis demonstrate the feasibility of drug sensitivity assessment and record-keeping tool for flight surgeons and astronauts in applying the recommended medications for situations arising in flight. The information on individual drug sensitivity will translate into personalized risk assessment for adverse drug reactions and treatment failures for each drug from the medication kit as well as predefined outcome. This will address the HHCs raised Concern of Clinically Relevant Unpredicted Effects of Medication as recently updated.

Description: Astronauts using high-force resistance training while weightless show a high-turnover remodeling state within the skeletal system, with resorption and formation biomarkers being elevated. One countermeasure for the skeletal health of astronauts includes an antiresorptive of the bisphosphonate (BP) drug class. We asked, does the combination of an anti-resorptive and high-force exercise during weightlessness have negative effects on bone remodeling and strength? In this study, we developed an integrated model to mimic the mechanical strain of exercise via cyclical loading (CL) in mice treated with the BP Zoledronate (ZOL) combined with hind limb unloading (HU) to simulate weightlessness. We hypothesized that ZOL prevents structural degradation from simulated weightlessness and that CL and ZOL interact to render CL less effective. Thirty-two C57BL/6 mice (male, 16 weeks old, n=8/group) were exposed to 3 weeks of either HU or normal ambulation (NA). Cohorts of mice received one subcutaneous injection of ZOL (45g/kg), or saline vehicle (VEH), prior to the start of HU. The right tibia was axially compressed in vivo 60x/day to 9N (+1200strain on the periosteal surface) and repeated 3x/week during HU. Left tibiae served as a within subject, non-compressed control. Ex vivo CT was performed on all subjects to determine cancellous and cortical architectural parameters. Static and dynamic histomorphometry were carried out for the left and right tibiae to determine osteoclast- and osteoblast relevant surfaces. Further, micro damage was assessed in select groups by basic-fuchsin staining to test whether CL had an effect. For all assays, a multivariate (2x2x2) ANCOVA model was used to account for body weight changes. Additionally, for the tibiae, we incorporated a random effect for the subject (hence, a mixed model) to account for observations of both left and right tibiae within each subject. P 〈 0.05 was considered significant. In the cancellous compartment of the proximal tibial metaphysis, we observed a main effect from each independent variable, as determined by structural and histomorphometric assays. Specifically, as expected, ZOL showed an increase in the cancellous bone volume to total volume fraction (BV/TV, +32%) and trabecular number (+18%) compared to the VEH. As expected, ZOL decreased osteoclast surface (OC/BS) by -45% compared to VEH. Surprisingly, ZOL reduced mineralizing surface (MS/BS) and bone formation rate (BFR), indicators of osteoblast activity, by -40% and -54%, respectively, compared to VEH. Altogether, ZOL-treated mice displayed a low turnover state of remodeling in the metaphysis. In the context of skeletal aging, we speculate that ZOL prevented age-related cancellous strut loss during the experiment. As a main effect, as expected, HU decreased BV/TV by - 31% via reductions in both trabecular thickness (-11%) and number (-22%) compared to NA controls. Additionally, HU decreased MS/BS by -38% and bone formation rate (BFR) by -50% compared to NA controls. Altogether, these data are consistent with structural degradation resulting from imbalanced remodeling that favors resorption. As a main effect, CL increased BV/TV by +15% via increased trabecular thickness (+12%) compared to the noncompressed limb. As expected, CL increased MS/BS (+20%) and BFR (+24%), indicating osteoblast mineralization contributed to bone gains. These data show that CL provided an anabolic stimulus to the cancellous tissue. We observed unique interactions in ZOL*CL and HU*CL. First, ZOL prevented CL-induced increases in BV/TV and trabecular number, as compared to VEH. In the context of skeletal aging, these data suggest no added benefit from CL in the ZOL-treated mice. Interestingly, no microdamage was observed in mice that were unloaded and treated with ZOL (independent of CL). Secondly, HU prevented CL-induced increases in BFR, as compared to NA controls. These data suggest that either exercise is less effective or the kinetics of formation are slower during simulated weightlessness. Osteoclast surface was unchanged by either treatment. Thus, in contrast to exercising astronauts, these data do not suggest a high-turnover state in the metaphysis. To assess mechanical properties as a function of HU or ZOL, we tested the left femur in three-point bending ex vivo. As expected, HU decreased stiffness (-30%) compared to NA, and ZOL increased stiffness compared to VEH (+28%). Interestingly, HU increased the post-yield displacement, related to collagenous tensile loading, compared to NA (+20%). ZOL increased yield force (+11%) and ultimate force (+17%), which seems to explain the significant effect of ZOL increasing total energy (work-to-fracture, +15%), while not affecting the post yield displacement. Taken together, ZOL did not have detrimental affect on mechanical properties. Our integrated model simulates the combination of weightlessness, exercise-induced mechanical strain, and anti-resorptive treatment that astronauts experience during space missions. We conclude that Zoledronate was an effective countermeasure against weightlessness-induced bone loss, though zoledronate, as well as weightlessness, rendered exercise-related mechanical loading less effective.

Description: No abstract available

Description: In this study, we aim to examine skeletal responses to simulated long-duration spaceflight (90 days) and weight-bearing recovery on bone loss using the ground-based hindlimb unloading (HU) model in adolescent (3-month old) male rats. We hypothesized that simulated microgravity leads to the temporal regulation of oxidative defense genes and pro-bone resorption factors, where there is a progression and eventual plateau; furthermore, early transient changes in these pathways precede skeletal adaptations.

Description: No abstract available

Description: Presentation to be presented at IWS 2017 on forecasting the change of renal stone occurrence rates in astronauts.

Description: No abstract available

Description: No abstract available

Description: Gravity transitions cause changes in the vestibulo-occular reflex (VOR), which manifests as poor gaze control, a decrement in dynamic visual acuity (the ability to maintain gaze while in motion), both of which are caused by retinal slip. Retinal slip, the inability to keep an image focused on the retina, can drive or worsen sensory conflict, resulting in motion sickness (MS). Currently 100% of returning crewmembers report MS symptoms, which might affect their ability to perform mission critical tasks immediately after landing. Reschke et al. (2007) demonstrate that stroboscopic vision goggles improve motion sickness onset and symptom severity in motion sickness driven by retinal slip.

Description: No abstract available

Description: No abstract available

Description: Carbon dioxide (CO2) levels on board the International Space Station (ISS) have typically averaged 2.3 to 5.3 mmHg, with large fluctuations occurring over periods of hours and days. CO2 has effects on cerebral vascular tone, resulting in vasodilation and alteration of cerebral blood flow (CBF). Increased CBF leads to elevated intracranial pressure (ICP), a factor leading to visual disturbances, headaches, and other central nervous system symptoms. Ultrasound of the optic nerve and optical coherence tomography (OCT) provide surrogate measurements of ICP; in-flight measurements of both were implemented as enhanced screening tools for the Visual Impairment/Intracranial Pressure (VIIP) syndrome. This analysis examines the relationships between ambient CO2 levels on ISS, ultrasound and OCT measures of the eye in an effort to understand how CO2 may possibly be associated with VIIP and to inform future analysis of in-flight VIIP data.

Description: BACKGROUND: Future human space travel will consist primarily of long-duration missions onboard the International Space Station (ISS) or exploration-class missions to Mars, its moons, or nearby asteroids. Astronauts participating in long-duration missions may be at an increased risk of oxidative stress and inflammatory damage due to radiation, psychological stress, altered physical activity, nutritional insufficiency, and hyperoxia during extravehicular activity. By studying one identical twin during his 1-year ISS mission and his ground-based twin, this work extends a current NASA-funded investigation to determine whether these spaceflight factors contribute to an accelerated progression of atherosclerosis. This study of twins affords a unique opportunity to examine spaceflight-related atherosclerosis risk that is independent of the confounding factors associated with different genotypes. PURPOSE: The purpose of this investigation was to determine whether biomarkers of oxidative and inflammatory stress are elevated during and after long-duration spaceflight and determine if a relation exists between levels of these biomarkers and structural and functional indices of atherosclerotic risk measured in the carotid and brachial arteries. These physiological and biochemical data will be extended by using an exploratory approach to investigate the relationship between intermediate phenotypes and risk factors for atherosclerosis and the metabolomic signature from plasma and urine samples. Since metabolites are often the indirect products of gene expression, we simultaneously assessed gene expression and DNA methylation in leukocytes. HYPOTHESIS: We predict that, compared to the ground-based twin, the space-flown twin will experience elevated biomarkers of oxidative stress and inflammatory damage, altered arterial structure and function, accelerated telomere shortening, dysregulation of genes associated with oxidative stress and inflammation, and a metabolic profile shift that is associated with elevated atherosclerosis risk factors. METHODS: In the space-flown twin, a panel of biomarkers of oxidative and inflammatory stress were measured in venous blood samples and in 24-h (in-flight) and 48-h (pre- and post-flight) urine pools collected twice before flight, six times during the mission (~FD15, 75, 180, 240, 300, 335), and early in the post-flight recovery phase (3-5 days after landing). We also measured metabolomic (targeted and untargeted approaches) and genomic markers (DNA methylation, mRNA gene expression, telomere length) in these samples. Arterial structure, assessed from measures of intima-media thickness, also were measured using standard clinical ultrasound at the same time points. Arterial function was assessed using brachial flow-mediated dilation, a well-validated measure used to assess endothelium-dependent vasodilation and a sensitive predictor of atherosclerotic risk, only before and after spaceflight. All of the same measures were obtained in the ground-based twin, but less frequently. DISCUSSION: All data collection has been completed for both the space-flown twin and the ground-based twin. Vascular structure and function measures have been analyzed, blood and urine samples have been batch-processed. Results from these individuals will be compared to each other, to data from other Twin Study investigations, and to the larger complement of subjects participating in the companion study currently ongoing in ISS astronauts.

Description: Carbon dioxide (CO2) originates from human metabolism and typically remains about 10-fold higher in concentration on the International Space Station (ISS) than at the earth's surface. There have been recurring complaints by crew members of episodes of "mental viscosity" adversely affecting their performance, and there is evidence from the ISS that associates CO2 levels with reports of headaches by crewmembers. Consequently, flight rules have been employed to control CO2 below 3 mm Hg, which is well below the existing Spacecraft Maximum Allowable Concentration (SMAC) of 10 mm Hg for 24-hour exposures, and 5.3 mm Hg for exposures of 7 to 180 days. Headaches, while sometime debilitating themselves, are also symptoms that can provide evidence that physiological defense mechanisms have been breached, and there is evidence that CO2 has effects at levels below the threshold for headaches. This concern appears to be substantiated in reports that CO2 at concentrations below 2 mm Hg substantially reduced some cognitive functions that are associated with the ability to make complex decisions in conditions that are characterized by volatility, uncertainty, complexity, ambiguity, and delayed feedback. These are conditions that could be encountered by crews in off-nominal situations or during the first missions beyond low earth orbit. Therefore, we set out to determine if decision-making under volatile, uncertain, confusing and ambiguous circumstances, where feedback is delayed or absent, is correlated with low levels of CO2 during acute exposures (several hours) in crew-like subjects and to determine if additional cognitive domains are sensitive to concentrations of CO2 at, or below, current ISS levels by using a test battery that is currently available onboard ISS. We enrolled 22 volunteers (8 females, 14 males) between the ages of 30-55 (38.8 +/- 7.0) years whose training and professional experience reflect that of the astronaut corps. Subjects were divided among 4 study groups. Exposures occurred in the 20-foot environmental chamber in Bldg 7 at JSC. Each group was exposed to each of four concentrations of CO2 (600, 1200, 2500, and 5000 ppm), and the exposure order was balanced across the groups which were randomly assigned to 4 possible complete exposure orders. Study participants and investigators were blinded to the exposure order. Each exposure lasted 4 hours and occurred on the same day each week for 4 consecutive weeks. Testing included the Strategic Management Simulation (SMS) methodology and the Cognition battery of psychometric measures that are being utilized aboard the ISS. Subjects participated in a familiarization session one week prior to the start of exposure sessions. Each exposure session followed the schedule noted in Figure 1 below. On the morning of each exposure, subjects completed the Cognition battery in a conference room at indoor ambient CO2 levels. Subjects then entered the exposure chamber and were acclimated to the environment for 15 minutes before completing another round of the Cognition battery. After a 20 minute rest, subject completed the approx.80 minute SMS. Subjects were allowed another 20 minute rest period before completing the final Cognition test battery in the exposure chamber. Subjects then returned to the conference room where they completed one final round of Cognition. Data from both testing methodologies are currently being analyzed and will be presented. Study investigators have not yet been unblinded to the coded exposure concentrations, but preliminary results suggest differences.

Description: NASA's Digital Astronaut Project is developing a bone physiology model to predict changes in bone mineral density over the course of a space mission. The model intends to predict bone loss due to exposure in microgravity as well as predicting bone maintenance due to mechanical stimulus generated by exercise countermeasures. These predictions will be used to inform exercise device efficacy and to help design exercise protocols that will maintain bone mineral density during long exposures to microgravity during spaceflight. The mechanical stimulus and the stresses that are exhibited on the bone are important factors for bone remodeling. These stresses are dependent on the types of exercise that are performed and vary throughout the bone due to the geometry. A primary area of focus for bone health is the proximal femur. This location is critical in transmitting loads between the upper and lower body and have been known to be a critical failure point in older individuals with conditions like osteoporosis.

Description: Long duration spaceflight causes a negative calcium balance and reduces bone density in astronauts. The potential for exposure to space radiation to contribute to lasting decrements in bone mass is not yet understood. Sustained changes to bone mass have a relatively long latency for development, however skin is a radiation sensitive organ and changes in skin gene expression may serve as an early radiation biomarker of exposures and may correlate with adverse effects on skeletal tissue. Previous studies have shown that FGF18 gene expression levels of hair follicles collected from astronauts on the ISS rose over time. In the hair follicle, FGF18 signaling mediates radioresistance in the telogen by arresting the cell cycle, and FGF18 has the potential to function as a radioprotector. In bone, FGF18 appears to regulate cell proliferation and differentiation positively during osteogenesis and negatively during chondrogenesis. Cellular defense responses to radiation are shared by a variety of organs, hence in this study, we examined whether radiation induced gene expression changes in skin may be predictive of the responses of skeletal tissue to radiation exposure. We have examined oxidative stress and growth arrest pathways in mouse skin and long bones by measuring gene expression levels via quantitative polymerase chain reaction (qPCR) after exposure to total body irradiation (TBI). To investigate the effects of irradiation on gene expression, we used skin and femora (cortical shaft) from the following treatment groups: control (normally loaded, sham-irradiated), and TBI (0.5 Gy Fe-56 600 MeV/n and 0.5 Gy H-1 150 MeV/n). Animals were euthanized one and 11 days post-IR. Statistical analysis was performed via a Student's ttest. In skin samples one day after IR, skin expression of FGF18 was significantly greater (3.8X) than sham-irradiated controls (3.8X), but did not differ 11 days post TBI. Expression levels of other radiation related genes (Nfe2l2, Trp53, Cdkn1a, FoxO3, Gadd45g, SOD1), was not different due to TBI at either time point. In bone (femora) TBI significantly increased (3.8X) expression of the pro-bone resorption cytokine, MCP-1, one day after TBI. FGF18 expression in skin and MCP- 1 expression in bone were found to be positively correlated (P less than 0.002, r=0.8779). Further, microcomputed tomography analysis of tibae from these animals showed reduced fractional cancellous bone volume (-21.7%) at 11 days post exposure. These results suggest that early radiation induced changes in FGF18 gene expression in skin may have value for predicting subsequent loss of cancellous bone mass.

Description: No abstract available

Description: No abstract available

Description: Upon return from long-duration spaceflight, 100% of crewmembers experience motion sickness (MS) symptoms. The interactions between crewmembers' adaptation to a gravitational transition, the performance decrements resulting from MS and/or use of promethazine (PMZ), and the constraints imposed by mission task demands could significantly challenge and limit an astronaut's ability to perform functional tasks during gravitational transitions. Stochastic resonance (SR) is "noise benefit": adding noise to a system might increase the information (examples to the left and above). Stochastic vestibular stimulation (SVS), or low levels of noise applied to the vestibular system, improves balance and locomotor performance (Goel et al. 2015, Mulavara et al. 2011, 2015). In hemi-lesioned rat models, Samoudi et al. 2012 found that SVS increased GABA release on the lesioned, but not the intact side. Activation of the GABA pathway is important in modulating MS and promoting adaptability (Cohen 2008) and was seen to reverse MS symptoms in rats after unilateral labyrinthectomy (Magnusson et al. 2000). Thus, SVS could be used to promote GABA pathways to reduce MS and promote adaptability, eliminate the need for PMZ or other performance-inhibiting drugs.

Description: No abstract available

Description: In order to minimize the loss of bone and muscle mass during spaceflight, the Multi-purpose Crew Vehicle (MPCV) will include an exercise device and enough free space within the cabin for astronauts to use the device effectively. The NASA Digital Astronaut Project (DAP) has been tasked with using computational modeling to aid in determining whether or not the available operational volume is sufficient for in-flight exercise.Motion capture data was acquired using a 12-camera Smart DX system (BTS Bioengineering, Brooklyn, NY), while exercisers performed 9 resistive exercises without volume restrictions in a 1g environment. Data were collected from two male subjects, one being in the 99th percentile of height and the other in the 50th percentile of height, using between 25 and 60 motion capture markers. Motion capture data was also recorded as a third subject, also near the 50th percentile in height, performed aerobic rowing during a parabolic flight. A motion capture system and algorithms developed previously and presented at last years HRP-IWS were utilized to collect and process the data from the parabolic flight [1]. These motions were applied to a scaled version of a biomechanical model within the biomechanical modeling software OpenSim [2], and the volume sweeps of the motions were visually assessed against an imported CAD model of the operational volume. Further numerical analysis was performed using Matlab (Mathworks, Natick, MA) and the OpenSim API. This analysis determined the location of every marker in space over the duration of the exercise motion, and the distance of each marker to the nearest surface of the volume. Containment of the exercise motions within the operational volume was determined on a per-exercise and per-subject basis. The orientation of the exerciser and the angle of the footplate were two important factors upon which containment was dependent. Regions where the exercise motion exceeds the bounds of the operational volume have been identified by determining which markers from the motion capture exceed the operational volume and by how much. A credibility assessment of this analysis was performed in accordance with NASA-STD-7009 prior to delivery to the MPCV program.

Description: No abstract available

Description: Ground based and ISS (International Space Station) exercise research have shown that axial loading via two-point loading at the shoulders and load quality (i.e. consistent load and at least 1:1 concentric to eccentric ratio) are extremely important to optimize musculoskeletal adaptations to resistance exercise. The Advanced Resistance Exercise Device (ARED) is on ISS now and is the "state of the art" for resistance exercise capabilities in microgravity; however, the ARED is far too large and power consuming for exploration vehicles. The single cable exercise device design selected for MPCV (Multi-Purpose Crew Vehicle), does not readily allow for the two-point loading at the shoulders.

Description: No abstract available

Description: Spaceflight impacts human physiology, including well documented immune system dysregulation. Diet, immune function, and the microbiome are interlinked, but diet is the only one of these factors that we have the ability to easily, and significantly, alter on Earth or during flight. As we understand dietary impacts on physiology more thoroughly, we may then improve the spaceflight diet to improve crew health and potentially reduce flight-associated physiological alterations. It is expected that increasing the consumption of fruits and vegetables and bioactive compounds (e.g.,omega-3 fatty acids, lycopene, flavonoids) and therefore enhancing overall nutritional intake from the nominal shelf-stable, fully-processed space food system could serve as a countermeasure to improve human immunological profiles, the taxonomic profile of the gut microbiota, and nutritional status, especially where currently dysregulated during spaceflight. This interdisciplinary study will determine the effect of the current shelf-stable spaceflight diet compared to an "enhanced" shelf-stable spaceflight diet (25% more foods rich in omega-3 fatty acids, lycopene, flavonoids, fruits, and vegetables). The NASA Human Exploration Research Analog (HERA) 2017 missions, consisting of closed chamber confinement, realistic mission simulation, in a high-fidelity mock space vehicle, will serve as a platform to replicate mission stressors and the dysregulated physiology observed in astronauts. Biosampling of crew members will occur at selected intervals, with complete dietary tracking. Outcome measures will include immune markers (e.g., peripheral leukocyte distribution, inflammatory cytokine profiles, T cell function), the taxonomic and metatranscriptomic profile of the gut microbiome, and nutritional status biomarkers and metabolites. Data collection will also include complete dietary tracking. Statistical evaluations will determine physiological and biochemical shifts in relation to nutrient in take and study phase. Beneficial improvements will provide evidence of the impact of diet on crew health and adaptation to this spaceflight analog, and will aid in the design and development of more-efficient targeted dietary interventions.

Description: No abstract available

Description: For future human exploration missions, NASA needs a health monitoring system composed of hardware that is compact, fully interoperable with an integrated data management system, and requires minimal consumables. Such a system will be achieved through the integration of small, easy to use biomedical sensors that will have the ability to measure, store and transmit physiological parameters during operational and ambulatory activity. Since 2012, the Canadian Space Agency (CSA) has been active in funding the development of wearable biomonitoring sensors. The Astroskin is the first prototype and consists of a shirt-based garment and headband with embedded sensors, and associated software and technology that measure vital signs, sleep quality and activity level of the wearer. NASA and CSA have been collaborating since 2014 to test and validate this system in a lab environment at Ames Research Center and more recently in the Human Exploration Research Analog (HERA) located at Johnson Spaceflight Center. Specific objectives of the HERA study were: 1) to assess the performance of the Astroskin biosensor system for long-term health monitoring (24-hours) capabilities and during exercise as a measure of crew fitness; 2) to obtain crew feedback on comfort and usability of the Astroskin system; 3) to demonstrate performance of Bluetooth communication during real-time transmission and for verification of data in this environment; and 4) to obtain baseline data for further development of algorithms and tools that facilitate decision support for diagnosing and monitoring of a sick or injured crewmember. HERA Campaign 3 included four missions (each 30-days in duration) with four crewmembers assigned to each mission. A total of 9 men and 7 women participated in the Astroskin evaluation that included continuous physiological monitoring (24-hours) on mission days MD-11, MD1 (high workload), MD15 (low workload), MD19, MD29, and MD+7. Mission days 19 and 29 also included 30 minutes of sub-maximal exercise on a cycle ergometer. Following each 24-hour monitoring session crew physiological data were downloaded to laptops and each crewmember completed a 28 question survey on their experiences with the Astroskin hardware and software. This presentation will focus on lessons learned from the HERA missions. Specifically it will address Astroskin system performance in terms of data loss and data quality (no comparison to lab standard devices), wireless communication with the onboard mobile device, crew usability and comfort, and future development of a next generation biomonitoring system.

Description: Astronauts experience Postflight disturbances in postural and locomotor control due to sensorimotor adaptation to the unique environment of spaceflight. These alterations might have adverse consequences if a rapid egress were required following a Mars landing or on return to Earth after a water landing. Currently, no operational countermeasure is targeted to mitigate Postflight balance and locomotor dysfunction.

Description: Despite evidence of bone loss during spaceflight and operational countermeasures to mitigate this loss, the subsequent risk of fracture among astronauts is not known. The physiologic process of diminished bone density and bone recovery during or following spaceflight is multifactorial. Such factors as age, sex, fracture history, and others may combine to increase fracture risk among astronauts. As part of the 2016 Bone Research and Clinical Advisory Panel (RCAP), the authors analyzed data collected on 338 NASA astronauts to describe the demographics, bone-relevant characteristics, and fracture history of the astronaut population. The majority of the population are male (n=286, 84.6%), have flown at least one mission (n=306, 90.5%), and were between the ages of 30 and 49 at first mission (n=296, 96.7% of those with at least one mission). Of the 338 astronauts, 241 (71.3%) experienced a fracture over the course of their lifetime. One hundred and five (43.5%) of these 241 astronauts only experienced a fracture prior to being selected into the Astronaut Corps, whereas 53 (22.0%) only experienced a fracture after selection as an astronaut. An additional 80 astronauts (33.2%) had both pre- and post-selection fractures. The remaining 3 astronauts had a fracture of unknown date, which could not be categorized as pre- or post-selection. Among the 133 astronauts with at least one post-selection fracture, males comprised 90.2% (n=120) compared to 84.5% of the entire Corps, and females accounted for 9.8% (n=13) compared to 15.4% of the Corps. Ninety-seven of the 133 astronauts with post-selection fractures (72.9%) had one fracture event, 22 (16.5%) had two fractures, and 14 (10.5%) had three or more fractures. Some astronauts with multiple fractures suffered these in a single event, such as an automobile accident. The 133 astronauts with a post-selection fracture accounted for a total of 188 fracture events. One hundred and four (78.2%) of astronauts with post-selection fractures experienced those fractures following their first mission (mean 12.7 +/- 11.1 years following first mission; range 14.0 days - 50.6 years). Additional analyses are ongoing and include examination of fracture history, skeletal site, mechanism, and type of fracture, age at time of fracture, time from spaceflight to fracture, as well as multivariable analysis comparing fracture events to non-events. The results of such analyses may reveal trends in risk factors for fracture among the astronaut corps that have yet to be systematically described through a corps-wide approach.

Description: Long-term exposure to microgravity causes sensorimotor adaptations that result in functional deficits upon returning to a gravitational environment. At landing, the vestibular system and the central nervous system, responsible for coordinating head and eye movements via the vestibulo-occular reflex (VOR), are adapted to microgravity and must re-adapt to the Earth's gravitational environment. This re-adaptation causes decrements in gaze control and dynamic visual acuity, with astronauts reporting oscillopsia and blurred vision. These effects are caused by retinal slip, or the inability to keep an image focused on their retina, which is thought to drive motion sickness symptoms experienced upon landing. Retinal slip can be estimated by dynamic visual acuity (DVA); visual acuity while in motion. Peters et al. (2011) find that DVA is worsened in astronauts by an average of 0.75 eye-chart lines one day after landing. Previously, the use of stroboscopic goggles has shown to be effective in minimizing motion sickness symptoms due to retinal slip (Reschke et al. 2007). In this study, we simulated the decrement in DVA caused by sensorimotor re-adaptation by using minifying lenses and then testing the efficacy of stroboscopic goggles in preventing retinal slip and improving DVA. Dynamic visual acuity is assessed using an oscillating chair developed in the Neuroscience Laboratory at JSC. This chair is motor-driven and oscillates vertically at 2 Hz with a vertical displacement of +/- 2 cm to simulate the vertical translations that occur while walking. As the subject is being oscillated, they are asked to discern the direction of Landolt-C optotypes of varying sizes and record their direction using a gamepad. The visual acuity thresholds are determined using an algorithm that alters the size of the optotype based on the previous responses of the subject using a forced-choice best parameter estimation that is able to rapidly converge on the threshold value. Visual acuity thresholds were determined both for static (seated) and dynamic (oscillating) conditions. Dynamic visual acuity is defined as the difference between the dynamic and static conditions. We found that healthy subjects (n=20) have a significantly impaired DVA while wearing the minifying lenses, demonstrating that the VOR is in an adaptive state and retinal slip is occurring. When subjects' acuity was tested wearing the stroboscopic goggles with the minifying lenses, there was no significant difference in their DVA compared to their baseline DVA. This suggests that stroboscopic goggles are preventing retinal slip and would function as an efficient countermeasure for VOR adaptations and thus help mitigate landing sickness symptoms experienced by long-duration crewmembers. These goggles might also be used to counter blurred vision (caused by retinal slip) experienced by crewmembers during launch where the vehicle vibrations are greatest. The stroboscopic effect could be built into a section of their head mounted displays on the visor of their helmets to be used in these high vibration situation if a mission critical task is necessary.

Description: In the realm of aerospace engineering and the physical sciences, we have developed laws of physics based on empirical and research evidence that reliably guide design, research, and development efforts. For instance, an engineer designs a system based on data and experience that can be consistently and repeatedly verified. This reproducibility depends on the consistency and dependability of the materials on which the engineer works and is subject to physics, geometry and convention. In life sciences and medicine, these apply as well, but individuality introduces a host of variables into the mix, resulting in characteristics and outcomes that can be quite broad within a population of individuals. This individuality ranges from differences at the genetic and cellular level to differences in an individuals personality and abilities due to sex and gender, environment, education, etc.

Description: A method of manufacturing and/or using a scaffold assembly for stem cell culture and tissue engineering applications is disclosed. The scaffold at least partially mimics a native biological environment by providing biochemical, topographical, mechanical and electrical cues by using an electroactive material. The assembly includes at least one layer of substantially aligned, electrospun polymer fiber having an operative connection for individual voltage application. A method of cell tissue engineering and/or stem cell differentiation that uses the assembly seeded with a sample of cells suspended in cell culture media, incubates and applies voltage to one or more layers, and thus produces cells and/or a tissue construct. In another aspect, the invention provides a method of manufacturing the assembly including the steps of providing a first pre-electroded substrate surface; electrospinning a first substantially aligned polymer fiber layer onto the first surface; providing a second pre-electroded substrate surface; electrospinning a second substantially aligned polymer fiber layer onto the second surface; and, retaining together the layered surfaces with a clamp and/or an adhesive compound.

Description: No abstract available

Description: Introduction: The probability of bone fracture during and after spaceflight is quantified to aid in mission planning, to determine required astronaut fitness standards and training requirements and to inform countermeasure research and design. Probability is quantified with a probabilistic modeling approach where distributions of model parameter values, instead of single deterministic values, capture the parameter variability within the astronaut population and fracture predictions are probability distributions with a mean value and an associated uncertainty. Because of this uncertainty, the model in its current state cannot discern an effect of countermeasures on fracture probability, for example between use and non-use of bisphosphonates or between spaceflight exercise performed with the Advanced Resistive Exercise Device (ARED) or on devices prior to installation of ARED on the International Space Station. This is thought to be due to the inability to measure key contributors to bone strength, for example, geometry and volumetric distributions of bone mass, with areal bone mineral density (BMD) measurement techniques. To further the applicability of model, we performed a parameter sensitivity study aimed at identifying those parameter uncertainties that most effect the model forecasts in order to determine what areas of the model needed enhancements for reducing uncertainty. Methods: The bone fracture risk model (BFxRM), originally published in (Nelson et al) is a probabilistic model that can assess the risk of astronaut bone fracture. This is accomplished by utilizing biomechanical models to assess the applied loads; utilizing models of spaceflight BMD loss in at-risk skeletal locations; quantifying bone strength through a relationship between areal BMD and bone failure load; and relating fracture risk index (FRI), the ratio of applied load to bone strength, to fracture probability. There are many factors associated with these calculations including environmental factors, factors associated with the fall event, mass and anthropometric values of the astronaut, BMD characteristics, characteristics of the relationship between BMD and bone strength and bone fracture characteristics. The uncertainty in these factors is captured through the use of parameter distributions and the fracture predictions are probability distributions with a mean value and an associated uncertainty. To determine parameter sensitivity, a correlation coefficient is found between the sample set of each model parameter and the calculated fracture probabilities. Each parameters contribution to the variance is found by squaring the correlation coefficients, dividing by the sum of the squared correlation coefficients, and multiplying by 100. Results: Sensitivity analyses of BFxRM simulations of preflight, 0 days post-flight and 365 days post-flight falls onto the hip revealed a subset of the twelve factors within the model which cause the most variation in the fracture predictions. These factors include the spring constant used in the hip biomechanical model, the midpoint FRI parameter within the equation used to convert FRI to fracture probability and preflight BMD values. Future work: Plans are underway to update the BFxRM by incorporating bone strength information from finite element models (FEM) into the bone strength portion of the BFxRM. Also, FEM bone strength information along with fracture outcome data will be incorporated into the FRI to fracture probability.

Description: This storyboard conceptualizes one scenario of an integrated medical system during a Mars exploration mission. All content is for illustrative purposes only and neither defines nor implies system design requirement.

Description: Exposure to the microgravity conditions of spaceflight causes astronauts to experience alterations in multiple physiological systems including sensorimotor disturbances, cardiovascular deconditioning, and loss of muscle mass and strength. Some or all of these changes might affect the ability of crewmembers to perform critical mission tasks immediately after landing on a planetary surface. The goal of our recently completed Functional Task Test (FTT) study was to determine the effects of spaceflight 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. The FTT is comprised of seven functional tests and a corresponding set of interdisciplinary physiological measures specifically targeting the sensorimotor, cardiovascular and muscular changes associated with exposure to spaceflight. Both Shuttle and International Space Station (ISS) astronauts were tested before and after spaceflight. Additionally, we conducted a supporting study in which subjects performed the FTT protocol before and after 70 days of 6 deg head-down bed rest, an analog for spaceflight. Two groups of bed rest subjects were studied: one group who performed aerobic and resistive exercise during bed rest using protocols similar to astronauts and one group who served as non-exercise controls. The bed rest analog allowed us to isolate the impact of body unloading without other spaceflight environmental factors on both functional tasks and on the underlying physiological factors that lead to decrements in performance, and then to compare those results with the results obtained in our spaceflight study. As an extension to the FTT study we collected data from one ISS crewmember who experienced 340 days in space using the same FTT protocol used previously to test spaceflight and bed rest subjects. Data were collected three times preflight and 1.7, 7.5 and 36.5 days after landing. The FTT one-year results will be presented at the meeting, and a comparison will be made with data previously obtained using the same protocol on astronauts tested before and after 6 months in space. Future work will focus on collecting data from additional subjects from one-year flights to gain a better assessment of extreme long-duration exposure to spaceflight on both functional measure of performance and physiological metrics.

Description: Acute effects of spaceflight on the cardiovascular system have been studied extensively, but the combined chronic effects of spaceflight and aging are not well understood. Preparation for and participation in space flight activities are potentially associated with cardiovascular disease risk factors (e.g., altered dietary and exercise habits, physical and emotional stress, circadian shifts, radiation). Further, astronauts who travel into space multiple times may be at an increased risk across their lifespan. However, comparing the risk of cardiovascular disease in astronauts to other large cohorts is difficult. For example, comparisons between astronauts and large national cohorts, such as the National Health and Nutrition Examination Survey and the National Health Information Survey, are hampered by significant differences in health status between astronauts and the general population, and most of these national studies fail to provide longitudinal data on population health. To address those limitations, NASA's Longitudinal Study of Astronaut Health previously sought to compare the astronauts to a cohort of civil servants employed at the Johnson Space Center. However, differences between the astronauts and civil servants at the beginning of the study, as well as differential follow up, limited the ability to interpret the results. To resolve some of these limitations, two unique cohorts of healthy workers, U.S. Air Force aviators and Cooper Center Longitudinal Study participants, have been identified as potential comparison populations for the astronaut corps. The Air Force cohort was chosen due to similarities in health at selection, screening, and some occupational exposures that Air Force aviators endure, many of which mirror that of the astronaut corps. The Cooper Clinic cohort, a generally healthy prevention cohort, was chosen for the vast array of clinical cardiovascular measures collected in a longitudinal manner complementary to those collected on astronauts, for a large number of subjects since 1971. The purpose of this study is to understand the incidence of cardiovascular disease outcomes and risk factors in the astronaut corps and determine whether the rates of disease are different than these two cohorts. The research questions are: 1. Are there differences in the incidence of CVD outcomes (MI, revascularization, and stroke) between each cohort and the NASA Astronaut cohort? 2. Are there differences in the incidence of CVD risks (hypertension, hyperlipidemia, arrhythmias, and diabetes) between each cohort and the NASA Astronaut cohort? 3. Are there differences between each cohort and the NASA Astronaut cohort in how CVD risk factors (e.g., lipids, behaviors) change across time? Collectively, results from these studies will enhance our understanding of how cardiovascular disease outcomes and risk factors change across time in astronauts compared to other longitudinally-studied healthy cohorts and determine if there are interactions between or additive effects of the occupational health effects of spaceflight exposure and normal aging.

Description: Human exploration missions to beyond low Earth orbit destinations such as Mars will require more autonomous capability compared to current low Earth orbit operations. For the medical system, lack of consumable resupply, evacuation opportunities, and real-time ground support are key drivers toward greater autonomy. Recognition of the limited mission and vehicle resources available to carry out exploration missions motivates the Exploration Medical Capability (ExMC) Element's approach to enabling the necessary autonomy. The Element's work must integrate with the overall exploration mission and vehicle design efforts to successfully provide exploration medical capabilities. ExMC is applying systems engineering principles and practices to accomplish its integrative goals. This talk will briefly introduce the discipline of systems engineering and key points in its application to exploration medical capability development. It will elucidate technical medical system needs to be met by the systems engineering work, and the structured and integrative science and engineering approach to satisfying those needs, including the development of shared mental and qualitative models within and external to the human health and performance community. These efforts are underway to ensure relevancy to exploration system maturation and to establish medical system development that is collaborative with vehicle and mission design and engineering efforts.

Description: No abstract available

Description: The Integrated Medical Model (IMM) is a MATLAB model that provides probabilistic assessment of the medical risk associated with human spaceflight missions.Different simulations or profiles can be run in which input conditions regarding both mission characteristics and crew characteristics may vary. For each simulation, the IMM records the total medical events that occur and treats each event with resources drawn from import scripts. IMM outputs include Total Medical Events (TME), Crew Health Index (CHI), probability of Evacuation (pEVAC), and probability of Loss of Crew Life (pLOCL).The Crew Health Index is determined by the amount of quality time lost (QTL). Previously, an optimization code was implemented in order to efficiently generate medical kits. The kits were optimized to have the greatest benefit possible, given amass and/or volume constraint. A 6-crew, 14-day lunar mission was chosen for the simulation and run through the IMM for 100,000 trials. A built-in MATLAB solver, mixed-integer linear programming, was used for the optimization routine. Kits were generated in 10% increments ranging from 10%-100% of the benefit constraints. Conditions wheremass alone was minimized, volume alone was minimized, and where mass and volume were minimizedjointly were tested.

Description: Due to the deconditioned state of crewmembers in the initial hours after landing, it is safer and more practical to perform a vision test while seated in a chair versus walking on a treadmill. The purpose of this study was to validate the ability of a manually operated oscillating chair to produce the oscillatory frequency and displacement equivalent of walking on a treadmill at a 4 mph pace. A fast Fourier transform (FFT)was performed on the vertical trunk acceleration to compare the peak and spread of the distribution of oscillation frequencies for each oscillating condition. Peak oscillation frequencies achieved with the manual chair were lower and more variable than those of treadmill walking and the automatic chair. This can mostly be attributed to operator fatigue. However, DVA scores across conditions were not significantly different, indicating that the manual chair can provide adequate vertical oscillation frequency and displacement with the added advantage of being portable enough for testing outside a laboratory. Furthermore the automatic chair very closely matches the oscillation frequency of treadmill walking, making it an ideal method for testing DVA in a laboratory setting.

Description: NASA astronauts on active status require medical certification for aircraft flying duties as well as readiness for long duration spaceflight training, launch to the International Space Station (ISS), and mission continuation during spaceflight operations. Behavioral fitness and adaptability is an inherent component of medical certification at NASA and requires a unique approach that spans the professional life-span of all active astronauts. TOPIC: This presentation will address the Behavioral Health and Performance (BHP) operations program at the Johnson Space Center. Components of BHP operations include astronaut selection, as well as annual, elective, preflight, inflight, and postflight BHP assessments. Each aspect of the BHP operations program will be discussed, with a focus on behavioral fitness determination and resultant outcomes. Specifically, astronaut selection generates a rating of suitability for long duration spaceflight as well as psychiatric qualification; annual, preflight and postflight BHP assessments provoke a decision regarding the presence of any aeromedical concerns; and inflight assessment requires a conclusion pertaining to mission impact. The combination of these elements provide for a unique, comprehensive approach to flight and spaceflight adaptability. APPLICATIONS: Attendees will understand the differing facets of NASA's comprehensive BHP operations program that occurs over the course of an astronaut's career and be able to compare and contrast this to the Adaptability Rating for Military Aviation (ARMA) and proposed models presented by others on this panel.

Description: As spaceflight durations have increased over the last four decades, the effects of microgravity on the human body have become far better understood, as have the exercise countermeasures. Through use of a combination of aerobic and resistive exercise devices, today's astronauts and cosmonauts are able to partially counter the losses in muscle strength, aerobic fitness, and bone strength that otherwise might occur during their missions on the International Space Station (ISS). Since 2000, the ISS has employed a variety of exercise equipment used as countermeasures to these risks. Providing reliable and available exercise systems has presented significant challenges due to the unique environment. In solving these, lessons have been learned that can inform development of future systems.

Description: No abstract available

Description: HRP Human Research Roadmap: Risk and Gap Risk of Adverse Health Outcomes and Decrements in Performance due to Inflight Medical Conditions. Med02 "Pharmacy" Gap: We do not have the capability to provide a safe and effective medication formulary for exploration missions delivering a recommendation for a chemically stable, safe, and effective medication formulary that will support the operational needs of exploration space missions research strategy evidence-based formulary and models innovative analytical tools and methodologies novel treatments and preventive measures Planned review by a panel of experts from the pharmaceutical industry, regulatory, and academic scientific communities Formulary Selection Formulary Potency and Shelf life Formulary Safety and Toxicity Novel Technology Proof-of-Concept Portable real-time chemical analysis Innovative drug development / design

Description: This joint European Space Agency (ESA) - NASA study will address adaptive changes in spatial orientation related to the subjective straight ahead and the use of a vibrotactile sensory aid to reduce perceptual errors. The study will be conducted before and after long duration expeditions to the International Space Station (ISS) to examine how spatial processing of target location is altered following exposure to microgravity. This study addresses the sensorimotor research gap to "determine the changes in sensorimotor function over the course of a mission and during recovery after landing."

Description: Long-duration spaceflight results in sensorimotor adaptations, which cause functional deficits during gravitational transitions, such as landing on a planetary surface after long-duration microgravity exposure. Both the vestibular system and the central nervous system are affected by gravitational transitions. These systems are responsible for coordinating head and eye movements via the vestibulo-ocular reflex (VOR) and go through an adaptation period upon exposure to microgravity. Consequently, they must also re-adapt to Earth's gravitational environment upon landing. This re-adaptation causes decrements in gaze control and dynamic visual acuity, with crewmembers reporting oscillopsia and blurred vision caused by retinal slip, or the inability to keep an image focused on their retina. This is thought to drive motion sickness symptoms experienced by most crewmembers following landing. Retinal slip can be estimated by dynamic visual acuity (DVA); visual acuity while in motion. Previously, DVA has been assessed in the laboratory where subjects walked at 6.4 km/hr on a motorized treadmill. Using this method, Peters et al. (2011) found that DVA is worsened in astronauts by an average of 0.75 eye-chart lines one day after landing. However, it is believed that re-adaptation occurs quickly and that DVA might be worse immediately upon re-exposure to a gravitational environment. Since many crewmembers are unable to walk safely upon landing, it was necessary to develop a method for replicating the vertical head movements associated with walking. In addition, the use of a chair to imitate the head displacement caused by walking isolates eye-head interactions without allowing for trunk and lower-body compensation, as seen with treadmill walking (Mulavara & Bloomberg 2003). Therefore, a modality for assessing DVA in the field within a few hours of landing was developed. In this study, we validated the ability of a manually operated oscillating chair to reproduce the oscillatory frequency of walking on a treadmill. Healthy non-astronaut subjects (n=14) participated in one test session and completed three static (seated) and three dynamic (walking/oscillated) visual acuity tests. DVA was assessed using a motorized treadmill, an automated oscillating chair, and a manually operated chair, both developed in the Neuroscience Laboratory at JSC. The automated chair was motor-driven and set to oscillate vertically at 2 Hz with a vertical displacement of +/- 5 cm to simulate vertical translation while walking. The manually operated chair was oscillated vertically by a test operator to the beat of a metronome at 120 beats/min (2 Hz) and a vertical displacement of approximately +/- 5 cm. As the subject was oscillated, they were asked to discern the direction gap of Landolt-C optotypes of varying sizes and verbally reported the direction while an operator recorded their response using a gamepad. Subjects were outfitted with accelerometers (sampling rate = 128 Hz) on their head, trunk and lumbar spine. A fast Fourier transform was performed on the vertical trunk acceleration to compare the peak and spread of the distribution of oscillation frequencies for each oscillating condition. The spread of the frequency distribution for the manual chair was not significantly different from either the treadmill or the automated chair. However, all three conditions had similar non-zero standard error values, suggesting a variance in head movement frequency which may affect DVA. The average oscillation frequency of the manual chair (1.85 Hz) was significantly different (=0.05) from that of treadmill walking (2.24 Hz), but not significantly different from that of the automated chair (1.85 Hz) and all three conditions had small standard errors (SEM = 0.04, 0.06, and 0.08 Hz for manual, treadmill, and automated respectively). This implies that both chairs oscillate at a frequency below that of treadmill walking, but are comparable to each other and reproducible across sessions. Additionally, DVA scores did not vary significantly across conditions. The smaller spread values of the oscillating chairs' frequencies indicated mitigation of variation induced by locomotor strategies, which enables better examination of the issue of VOR adaptation. Furthermore, due to the deconditioned state of crewmembers in the initial hours after landing, it is easier to transport a manual bouncing chair into the field and safer to perform a vision test while seated in a chair versus walking on a treadmill. Therefore, the manually oscillating chair has been deemed to meet and exceed the DVA testing capabilities previously obtained by treadmill walking.

Description: Future exploration missions will be the first time humanity travels beyond Low Earth Orbit (LEO) since the Apollo program, taking us to cis-lunar space, interplanetary space, and Mars. These long-duration missions will cover vast distances, severely constraining opportunities for emergency evacuation to Earth and cargo resupply opportunities. Communication delays and blackouts between the crew and Mission Control will eliminate reliable, real-time telemedicine consultations. As a result, compared to current LEO operations onboard the International Space Station, exploration mission medical care requires an integrated medical system that provides additional in-situ capabilities and a significant increase in crew autonomy. The Medical System Concept of Operations for Mars Exploration Missions illustrates how a future NASA Mars program could ensure appropriate medical care for the crew of this highly autonomous mission. This Concept of Operations document, when complete, will document all mission phases through a series of mission use case scenarios that illustrate required medical capabilities, enabling the NASA Human Research Program (HRP) Exploration Medical Capability (ExMC) Element to plan, design, and prototype an integrated medical system to support human exploration to Mars.

Description: The primary objective was to determine whether a high sodium diet during bed rest induced alterations in vascular compliance and was related to the incidence of VIIP. Ocular structural and functional measures and vascular ultrasound of the head and neck were acquired in bed rest subjects completing 10-14 days in 6deg head-down tilt.

Description: Visual Impairment/Intracranial Pressure (VIIP) is a top human spaceflight risk for which NASA does not currently have a proven mitigation strategy. Thigh cuffs (Braslets) and lower body negative pressure (LBNP; Chibis) devices have been or are currently being evaluated as a means to reduce VIIP signs and symptoms, but these methods alone may not provide sufficient relief of cephalic venous congestion and VIIP symptoms. Additionally, current LBNP devices are too large and cumbersome for their systematic use as a countermeasure. Therefore, a novel approach is needed that is easy to implement and provides specific relief of symptoms. This investigation will evaluate an impedance threshold device (ITD) as a VIIP countermeasure.

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Description: MOTIVATION: Spaceflight countermeasures mitigate the harmful effects of the space environment on astronaut health and performance. Exercise has historically been used as a countermeasure to physical deconditioning, and additional countermeasures including lower body negative pressure, blood flow occlusion and artificial gravity are being researched as countermeasures to spaceflight-induced fluid shifts. The NASA Digital Astronaut Project uses computational models of physiological systems to inform countermeasure design and to predict countermeasure efficacy.OVERVIEW: Computational modeling supports the development of the exercise devices that will be flown on NASAs new exploration crew vehicles. Biomechanical modeling is used to inform design requirements to ensure that exercises can be properly performed within the volume allocated for exercise and to determine whether the limited mass, volume and power requirements of the devices will affect biomechanical outcomes. Models of muscle atrophy and bone remodeling can predict device efficacy for protecting musculoskeletal health during long-duration missions. A lumped-parameter whole-body model of the fluids within the body, which includes the blood within the cardiovascular system, the cerebral spinal fluid, interstitial fluid and lymphatic system fluid, estimates compartmental changes in pressure and volume due to gravitational changes. These models simulate fluid shift countermeasure effects and predict the associated changes in tissue strain in areas of physiological interest to aid in predicting countermeasure effectiveness. SIGNIFICANCE: Development and testing of spaceflight countermeasure prototypes are resource-intensive efforts. Computational modeling can supplement this process by performing simulations that reduce the amount of necessary experimental testing. Outcomes of the simulations are often important for the definition of design requirements and the identification of factors essential in ensuring countermeasure efficacy.

Description: No abstract available

Description: The previous manned missions to the Moon represent milestones of human ingenuity, perseverance, and intellectual curiosity. However, one of the major ongoing concerns is the array of hazards associated with lunar surface dust. Not only did the dust cause mechanical and structural integrity issues with the suits, the dust 'storm' generated upon reentrance into the crew cabin caused "lunar hay fever" and "almost blindness [1-3]" (Figure 1). It was further reported that the allergic response to the dust worsened with each exposure [4]. The lack of gravity exacerbated the exposure, requiring the astronauts to wear their helmet within the module in order to avoid breathing the irritating particles [1]. Due to the prevalence of these high exposures, the Human Research Roadmap developed by NASA identifies the Risk of Adverse Health and Performance Effects of Celestial Dust Exposure as an area of concern [5]. Extended human exploration will further increase the probability of inadvertent and repeated exposures to celestial dusts. Going forward, hazard assessments of celestial dusts will be determined through sample return efforts prior to astronaut deployment. Studies on the lunar highland regolith indicate that the dust is not only respirable but also reactive [2, 6-9], and previous studies concluded that it is moderately toxic; generating a greater response than titanium oxide but a lower response than quartz [6]. The presence of reactive oxygen species (ROS) on the surface of the dust has been implicated. However, there is actually little data related to physicochemical characteristics of particulates and pulmonary toxicity, especially as it relates to celestial dust exposure. As a direct response to this deficit, the present study evaluates the role of a particulate's innate geochemical features (e.g., bulk chemistry, internal composition, morphology, size, and reactivity) in generating adverse toxicological responses in vitro and in vivo. This highly interdisciplinary study evaluates the relative toxicity of six meteorite samples representing either basalt or regolith breccia on the surfaces of the Moon, Mars, and Asteroid 4Vesta (Table 1); three potential candidates for future human exploration or colonization. Terrestrial mid-ocean ridge basalt (MORB) is also used for comparison as a control sample.

Description: Launching, landing, flight route, expeditions, Soyuz, near Kazakhstan USOS Crew Surgeon -Quarantine and direct care to crew before launch, then present in close proximity to launch for abort. IP Crew Surgeon -same Deputy Crew Surgeon -Back up for crew surgeon, care for immediate family, stationed at airport for helicopter abort response Russian based US doctor -Coordinate with SOS staff USOS Crew Surgeon -Nominal helicopter response and initial medical care and support during return on gulfstreamIPcenter dotP Crew Surgeon -same Deputy Crew Surgeon -Ballistic helicopter support Russian based US doctor -Coordinate with SOS staff Direct return doctor -Direct medical care on return flight

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