ALBERT

Description: Sensorimotor changes such as postural and gait instabilities can affect the functional performance of astronauts when they transition across different gravity environments. We are developing a method, based on stochastic resonance (SR), to enhance information transfer by applying non-zero levels of external noise on the vestibular system (vestibular stochastic resonance, VSR). Our previous work has shown the advantageous effects of VSR in a balance task of standing on an unstable surface. This technique to improve detection of vestibular signals uses a stimulus delivery system that is wearable or portable and provides imperceptibly low levels of white noise-based binaural bipolar electrical stimulation of the vestibular system. The goal of this project is to determine optimal levels of stimulation for SR applications by using a defined vestibular threshold of motion detection. A series of experiments were carried out to determine a robust paradigm to identify a vestibular threshold that can then be used to recommend optimal stimulation levels for SR training applications customized to each crewmember. Customizing stimulus intensity can maximize treatment effects. The amplitude of stimulation to be used in the VSR application has varied across studies in the literature such as 60% of nociceptive stimulus thresholds. We compared subjects' perceptual threshold with that obtained from two measures of body sway. Each test session was 463s long and consisted of several 15s sinusoidal stimuli, at different current amplitudes (0-2 mA), interspersed with 20-20.5s periods of no stimulation. Subjects sat on a chair with their eyes closed and had to report their perception of motion through a joystick. A force plate underneath the chair recorded medio-lateral shear forces and roll moments. First we determined the percent time during stimulation periods for which perception of motion (activity above a pre-defined threshold) was reported using the joystick, and body sway (two standard deviation of the noise level in the baseline measurement) was detected by the sensors. The percentage time at each stimulation level for motion detection was normalized with respect to the largest value and a logistic regression curve fit was applied to these data. The threshold was defined at the 50% probability of motion detection. Comparison of threshold of motion detection obtained from joystick data versus body sway suggests that perceptual thresholds were significantly lower, and were not impacted by system noise. Further, in order to determine optimal stimulation amplitude to improve balance, two sets of experiments were carried out. In the first set of experiments, all subjects received the same level of stimuli and the intensity of optimal performance was projected back on subjects' vestibular threshold curve. In the second set of experiments, on different subjects, stimulation was administered from 20-400% of subjects' vestibular threshold obtained from joystick data. Preliminary results of our study show that, in general, using stimulation amplitudes at 40-60% of perceptual motion threshold improved balance performance significantly compared to control (no stimulation). The amplitude of vestibular stimulation that improved balance function was predominantly in the range of +/- 100 to +/- 400 micro A. We hypothesize that VSR stimulation will act synergistically with sensorimotor adaptability (SA) training to improve adaptability by increasing utilization of vestibular information and therefore will help us to optimize and personalize a SA countermeasure prescription. This combination will help to significantly reduce the number of days required to recover functional performance to preflight levels after long-duration spaceflight.

Description: The cephalad fluid shift induced by microgravity has been hypothesized to cause an elevation in intracranial pressure (ICP) and contribute to the development of the Visual Impairment/Intracranial Pressure (VIIP) syndrome, as experienced by some astronauts during long-duration space flight. Elevated ambient partial pressure of carbon dioxide (PCO2) on ISS may also raise ICP and contribute to VIIP development. We seek to determine if the combination of mild CO2 exposure, similar to that occurring on the International Space Station, with the cephalad fluid shift induced by head-down tilt, will induce ophthalmic and cerebral blood flow changes similar to those described in the VIIP syndrome. We hypothesize that mild hypercapnia in the head-down tilt position will increase choroidal blood volume and cerebral blood flow, raise intraocular pressure (IOP), and transiently reduce visual acuity as compared to the seated or the head-down tilt position without elevated CO2, respectively.

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

Description: 1. Project Overview Visual impairment and intracranial pressure (VIIP) is a spaceflight-associated medical condition affecting at least a third of American astronauts who have flown International Space Station (ISS) missions. VIIP is defined primarily by visual acuity deficits and anatomical changes to eye structures. In some astronauts, eye-related changes do not revert back to the preflight state upon return to Earth. Our team will study some of the possible causes for this syndrome. This will be achieved by reviewing previous astronaut data for factors that may predispose astronauts to higher rates of developing this syndrome or greater severity of symptoms. Additionally, we will conduct 3 separate experiments that will characterize vessels in the head and neck and measure the effects of the experimental conditions on ocular structures and function. 2. Technical Summary The primary objective of this study is to determine whether vascular compliance is altered by spaceflight and whether such adaptations are related to the incidence of the VIIP. In particular, we will measure ocular parameters and vascular compliance in vessels of the head and neck in astronauts who have no spaceflight experience (Ground), in astronauts before, during, and after spaceflight (Flight), and in bed rest subjects with conditions similar to spaceflight (Bed Rest). Additionally, we will analyze astronaut data from the Lifetime Surveillance of Astronaut Health (LSAH) archives to determine which factors might be predictive of the development of VIIP (Data Mining). The project will be conducted in four separate, but related parts. Hypothesis The central hypothesis of this proposal is that exposure to the spaceflight environment aboard the ISS may lead to development of the VIIP syndrome (increased intracranial pressure and impaired visual acuity) and that this may be related to alterations in venous and/or arterial compliance in the head and neck. Specific Aims 1. To determine whether noninvasive measures of venous and arterial compliance are altered by long-duration spaceflight exposure in ISS astronauts and whether these changes are related to the development of the VIIP syndrome. (Flight) 2. To determine whether previous spaceflight experience predispose astronauts to lower venous compliance and/or the development of the VIIP syndrome. (Ground + Flight) 3. To use a 14-day, 6deg head-down-tilt bed rest as a model of spaceflight, to evaluate the effect of aging on vascular compliance using a subject population similar to younger (25-35 yr) and older (45-55 yr) astronaut cohorts. (Bed Rest) 4. To determine what factors contribute to lower venous compliance and/or the development of the VIIP syndrome in astronauts. (Data Mining) 3. Earth Applications This research may inform the mechanisms that regulate blood/fluid flow in and out of the brain in the head and neck. This information may help with understanding of the mechanisms behind idiopathic intracranial hypertension. 4. Link to NASA Taskbook Entry Not Yet Available

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

Description: Ionizing radiation produces several radiolytic species such as.OH, e-aq, and H. when interacting with biological matter. Following their creation, radiolytic species diffuse and chemically react with biological molecules such as DNA. Despite years of research, many questions on the DNA damage by ionizing radiation remains, notably on the indirect effect, i.e. the damage resulting from the reactions of the radiolytic species with DNA. To simulate DNA damage by ionizing radiation, we are developing a step-by-step radiation chemistry code that is based on the Green's functions of the diffusion equation (GFDE), which is able to follow the trajectories of all particles and their reactions with time. In the recent years, simulations based on the GFDE have been used extensively in biochemistry, notably to simulate biochemical networks in time and space and are often used as the "gold standard" to validate diffusion-reaction theories. The exact GFDE for partially diffusion-controlled reactions is difficult to use because of its complex form. Therefore, the radial Green's function, which is much simpler, is often used. Hence, much effort has been devoted to the sampling of the radial Green's functions, for which we have developed a sampling algorithm This algorithm only yields the inter-particle distance vector length after a time step; the sampling of the deviation angle of the inter-particle vector is not taken into consideration. In this work, we show that the radial distribution is predicted by the exact radial Green's function. We also use a technique developed by Clifford et al. to generate the inter-particle vector deviation angles, knowing the inter-particle vector length before and after a time step. The results are compared with those predicted by the exact GFDE and by the analytical angular functions for free diffusion. This first step in the creation of the radiation chemistry code should help the understanding of the contribution of the indirect effect in the formation of DNA damage and double-strand breaks.

Description: Current and future Space exploration missions and extended human presence in space aboard the ISS will expose crew to risks that differ both quantitatively and qualitatively from those encountered before by space travelers and will impose an unknown risk of safety and crew health. The technology development challenges for optimizing therapeutics in space must include the development of pharmaceuticals with extended stability, optimal efficacy and bioavailability with minimal toxicity and side effects. Innovative technology development goals may include sustained/chronic delivery preventive health care products and vaccines, low-cost highefficiency noninvasive, nonoral dosage forms with radioprotective formulation matrices and dispensing technologies coupled with selfreliant tracking technologies for quality assurance and quality control assessment. These revolutionary advances in pharmaceutical technology will assure human presence in space and healthy living on Earth. Additionally, the Joint Commission on Accreditation of Healthcare Organizations advocates the use of health information technologies to effectively execute all aspects of medication management (prescribing, dispensing, and administration). The advent of personalized medicine and highly streamlined treatment regimens stimulated interest in new technologies for medication management. Intelligent monitoring devices enhance medication accountability compliance, enable effective drug use, and offer appropriate storage and security conditions for dangerous drug and controlled substance medications in remote sites where traditional pharmacies are unavailable. These features are ideal for Exploration Medical Capabilities. This presentation will highlight current novel commercial offtheshelf (COTS) intelligent medication management devices for the unique dispensing, therapeutic drug monitoring, medication tracking, and drug delivery demands of exploration space medical operations.

Description: The environment of space results in a multitude of challenges to the human physiology that present barriers to extended habitation and exploration. Over 40 years of investigation to define countermeasures to address space flight adaptation has left gaps in our knowledge regarding mitigation strategies partly due to the lack of investigative tools, monitoring strategies, and real time diagnostics to understand the central causative agent(s) responsible for physiologic adaptation and maintaining homeostasis. Spaceflight-adaptation syndrome is the combination of space environmental conditions and the synergistic reaction of the human physiology. Our work addresses the role of oxidative stress and damage (OSaD) as a negative and contributing Risk Factor (RF) in the following areas of combined spaceflight related dysregulation: i) radiation induced cellular damage [1], [2] ii) immune impacts and the inflammatory response [3], [4] and iii) varicella zoster virus (VZV) reactivation [5]. Varicella-zoster (VZV)/Chicken Pox virus is a neurotropic human alphaherpesvirus resulting in varicella upon primary infection, suppressed by the immune system becomes latent in ganglionic neurons, and reactivates under stress events to re-express in zoster and possibly shingles. Our laboratory has developed a complex threedimensional (3D) normal human neural tissue model that emulates several characteristics of the human trigeminal ganglia (TG) and allows the study of combinatorial experimentation which addresses, simultaneously, OSaD associated with Spaceflight adaptation and habitation [6].

Description: The array of physiological changes that occur when humans venture into space for long periods presents a challenge to future exploration. The changes are conventionally investigated independently, but a complete understanding of adaptation requires a conceptual basis founded in intergrative physiology, aided by appropriate mathematical modeling. NASA is in the early stages of developing such an approach.

Description: Planetary Robotic and Human Spaceflight Exploration Humans are exposed to a great variety of hazards in the space environment. These include the effects of weightlessness, radiation, isolation and confinement, altered day-night cycles, and others. These inherent hazards have both physiological and behavioral consequences. The adaptive capabilities of humans in these situations is remarkable, and often exceed our expectations. However, the demanding environment and challenging operational pace can push some of these adaptive processes to their limits. The NASA Human Research Program (HRP) is tasked with mitigating the most serious of these effects on human health, safety, and performance, in long-duration space flight. This can involve the development and deployment of physiological countermeasures, better understanding of the physiological alterations and avoidance of exacerbating situations, inputs to the design of future spacecraft to minimize risks, and in some cases the awareness that some level of risk might have to be accepted based on the resulting consequences and their likelihood. HRP has identified a few areas that are of special concern due to their severity, lack of understanding of underlying causes, or potential for negative impact on health or performance. Some of these areas are visual impairment possibly due to increased intracranial pressure, behavioral and performance problems due to sleep deficits and isolation, and acute and chronic effects of radiation. These problems can, if not addressed, be expected to increase on longer and more distant missions. The evidence from spaceflight, laboratory, and analog studies that supports the selection of the most critical risks will be discussed. Current and planned research programs that address these risks, and their anticipated outcomes, will also be described.

Description: The Contributing Factor Map (CFM) is a visual representation of a taxonomy of factors influencing human health and performance in space. This presentation will give an overview of its development and its structure. It will describe various uses of the CFM that can support researchers working within the Human Research Program (HRP) Architecture of Evidence-Risk-Gap-Task-Deliverable. For example, during the Risk phase, the CFM can be used as a "menu" to help formulate a qualitative model of the factors contributing to specific consequences of concern. It provides a reference set of factors from across the operational, vehicle design, and human domains that otherwise might not be considered if approaching a risk from a specific domain perspective. Using the CFM as a reference can increase awareness of potential cross-disciplinary collaborations for overall risk mitigation. The CFM can also be used as a framework for identifying gaps in knowledge about a risk. This identification can support the subsequent development of gaps and tasks comprising the research plan aimed at risk mitigation. Examples of these types of applications of the CFM will be discussed and information on the support available to researchers in using it will be provided.

Description: After an initial stone episode persons are at increased risk for future stone formation. A systematic approach is required to monitor the efficacy of treatment and preventive measures, and to assess the risk of developing new stones. This is important for persons working in critical jobs or austere environments, such as astronauts. A literature review of the current standards of care for renal stone monitoring and imaging was done. Military and civil aviation standards were also reviewed, as well as the medical precedents from the space program. Additionally, a new, more effective, renal stone ultrasound protocol has been developed. Using this work, a monitoring algorithm was proposed that takes into consideration the unique mission and operational environment of spaceflight. The approach to imaging persons with history of renal stones varies widely in the literature. Imaging is often done yearly or biannually, which may be too long for mission critical personnel. In the proposed algorithm astronauts with a history of renal stone, who may be under consideration for assignment, are imaged by a detailed, physiciandriven, ultrasound protocol. Unassigned personnel are monitored by yearly ultrasound and urine studies. Any positive ultrasound study is then followed by low-dose renal computed tomography scan. Other criteria are also established. The proposed algorithm provides a balanced approach between efficacy and reduced radiation exposure for the monitoring of astronauts with a renal stone history. This may eventually allow a transition from a risk-averse, to a risk-modifying approach that can enable continued service of individuals with history of renal stone that have adequately controlled risk factors.

Description: Long duration missions outside of low Earth orbit will present unique challenges to the maintenance of human health. Stressors with physiologic and psychological impacts are inherent in exploration missions, including reduced gravity, increased radiation, isolation, limited habitable volume, circadian disruptions, and cabin atmospheric changes. Operational stressors such as mission timeline and extravehicular activities must also be considered, and these varied stressors may act in additive or synergistic fashions. Should changes to physiology or behavior manifest as a health condition, the rendering of care in an exploration environment must also be considered. Factors such as the clinical background of the crew, inability to evacuate to Earth in a timely manner, communication delay, and limitations in available medical resources will have an impact on the assessment and treatment of these conditions. The presentations associated with this panel will address these unique challenges from the perspective of several elements of the NASA Human Research Program, including Behavioral Health and Performance, Human Health Countermeasures, Space Radiation, and Exploration Medical Capability.

Description: Future human space travel will primarily consist of long duration missions onboard the International Space Station or exploration class missions to Mars, its moons, or nearby asteroids. Current evidence suggests that long duration missions might increase risk of permanent ocular structural and functional changes, possibly due to increased intracranial pressure resulting from a spaceflight-induced cephalad (headward) fluid shift.

Description: Long-duration space flight carries the risk of developing Visual Impairment and Intracranial Pressure (VIIP) syndrome, a spectrum of ophthalmic changes including posterior globe flattening, choroidal folds, distension of the optic nerve sheath (ONS), optic nerve kinking and potentially permanent degradation of visual function. The slow onset of VIIP, its chronic nature, and certain clinical features strongly suggest that biomechanical factors acting on the ONS play a role in VIIP. Here we measure several relevant ONS properties needed to model VIIP biomechanics. The ONS (meninges) of fresh porcine eyes (n7) was reflected, the nerve proper was truncated near the sclera, and the meninges were repositioned to create a hollow cylinder of meningeal connective tissue attached to the posterior sclera. The distal end was cannulated, sealed, and pressure clamped (mimicking cerebrospinal fluid [CSF] pressure), while the eye was also cannulated for independent control of intraocular pressure (IOP). The meninges were inflated (CSF pressure cycling 7-50 mmHg) while ONS outer diameter was imaged. In another set of experiments (n4), fluid permeation rate across the meninges was recorded by observing the drainage of an elevated fluid reservoir (30 mmHg) connected to the meninges. The ONS showed behavior typical of soft tissues: viscoelasticity, with hysteresis in early preconditioning cycles and repeatable behavior after 4 cycles, and nonlinear stiffening, particularly at CSF pressures 15 mmHg (Figure). Tangent moduli measured from the loading curve were 372 101, 1199 358, and 2050 379 kPa (mean SEM) at CSF pressures of 7, 15 and 30 mmHg, respectively. Flow rate measurements through the intact meninges at 30mmHg gave a permeability of 1.34 0.46 lmincm2mmHg (mean SEM). The ONS is a tough, strain-stiffening connective tissue that is surprisingly permeable. The latter observation suggests that there could be significant CSF drainage through the ONS into the orbit, likely important for CSF transport in the optic nerve. These experimental measurements, extended to human eyes, are informing computational models of the pathophysiology and biomechanics of the ONS in VIIP syndrome.

Description: No abstract available

Description: Develop a compact low-power neutron spectrometer that uniquely identifies neutrons in the mixed radiation field expected on crewed deep-space missions. Secondary neutrons are generated by cosmic rays striking heavy crewed spacecraft as well as lunar and planetary surfaces1,2. It has been shown that secondary neutrons can account for up to 50% if the total dose-equivalent received by the crew.

Description: No abstract available

Description: Arterial health may be affected by microgravity or ground based analogs of spaceflight, as shown by an increase in thoracic aorta stiffness1. Head-down tilt bed rest (HDTBR) is often used as a ground-based simulation of spaceflight because it induces physiological changes similar to those that occur in space2, 3. This abstract details an analysis of arterial stiffness (a subclinical measure of atherosclerosis), the distensibility coefficient (DC), and the pressure-strain elastic modulus (PSE) of the arterial walls during HDTBR. This project may help determine how spaceflight differentially affects arterial function in the upper vs. lower body.

Description: After space flight there are changes in multiple physiological systems including: Cardiovascular function; Sensorimotor function; and Muscle function. How do changes in these physiological system impact astronaut functional performance?

Description: Under the conditions of microgravity, astronauts lose bone mass at a rate of 1% to 2% a month, particularly in the lower extremities such as the proximal femur: (1) The most commonly used countermeasure against bone loss has been prescribed exercise, (2) However, current exercise countermeasures do not completely eliminate bone loss in long duration, 4 to 6 months, spaceflight, (3,4) leaving the astronaut susceptible to early onset osteoporosis and a greater risk of fracture later in their lives. The introduction of the Advanced Resistive Exercise Device, coupled with improved nutrition, has further minimized the 4 to 6 month bone loss. But further work is needed to implement optimal exercise prescriptions, and (5) In this light, NASA's Digital Astronaut Project (DAP) is working with NASA physiologists to implement well-validated computational models that can help understand the mechanisms of bone demineralization in microgravity, and enhance exercise countermeasure development.

Description: Long duration spaceflight (i.e., 22 days or longer) has been associated with changes in sensorimotor systems, resulting in difficulties that astronauts experience with posture control, locomotion, and manual control. It is unknown whether and how spaceflight impacts sensorimotor brain structure and function, and whether such changes may potentially underlie behavioral effects. Long duration head down tilt bed rest has been used repeatedly as an exclusionary analog to study microgravity effects on the sensorimotor system [1]. Bed rest mimics microgravity in body unloading and bodily fluid shifts. We are currently testing sensorimotor function, brain structure, and brain function pre and post a 70day bed rest period. We will acquire the same measures on NASA crewmembers starting in 2014. Here we present the results of the first eight bed rest subjects. Subjects were assessed at 12 and 7 days before, at 7, 30, and ~70 days in, and at 8 and 12 days post 70 days of bed rest at the NASA bed rest facility, UTMB, Galveston, TX, USA. At each time point structural MRI scans (i.e., high resolution T1weighted imaging and Diffusion Tensor Imaging (DTI)) were obtained using a 3T Siemens scanner. Focal changes over time in gray matter density were assessed using the voxel based morphometry 8 (VBM8) toolbox under SPM. Focal changes in white matter microstructural integrity were assessed using tract based spatial statistics (TBSS) as part of the FMRIB software library (FSL). TBSS registers all DTI scans to standard space. It subsequently creates a study specific white matter skeleton of the major white matter tracts. Nonparametric permutation based ttests and ANOVA's were used for voxelwise comparison of the skeletons. For both VBM and TBSS, comparison of the two pre bed rest measurements did not show significant differences. VBM analysis revealed decreased gray matter density in bilateral areas including the frontal medial cortex, the insular cortex and the caudate nucleus from pre to in bed rest. Over the same time period, there was an increase in gray matter density in the cerebellum, occipital, and parietal cortices. The majority of these changes did not recover from during to post bed rest. TBSS analyses will also be presented. Extended bed rest, which is an analog for microgravity, can result in gray matter changes and potentially in microstructural white matter changes in areas that are important for neuromotor behavior and cognition. These changes did not recover at two weeks post bed rest. These results have significant public health implications, and will also aid in interpretation of our future data obtained pre and post spaceflight. Whether the effects of bed rest wear off at longer times post bed rest, and if they are associated with behavior are important questions that warrant further research.

Description: No abstract available

Description: The objective is to define successive bed rest campaigns leading to a potential VIIP (Vision Impairment and Intracranial Pressure) countermeasure. To determine if the analog is successful, changes need to occur in the following outcome measures (dependent variables): Intracranial pressure; Retinal nerve fiber layer; Choroidal engorgement; Globe flattening; Axial biometry; Optic nerve sheath diameter distention; Cycloplegic refraction; Visual acuity. Study parameters (independent variables) to include: CO2; Sodium; Exercise (resistive & aerobic); Strict tilt angle.

Description: To investigate the pathways and kinetics of protein aggregation to allow accurate predictive modeling of the process and evaluation of potential inhibitors to prevalent diseases including cataract formation, chronic traumatic encephalopathy, Alzheimer's Disease, Parkinson's Disease and others.

Description: The area of Space Health and Medicine is one of the NASA's Space Technology Grand Challenges. Space is an extreme environment which is not conducive to human life. The extraterrestrial environment can result in the deconditioning of various human physiological systems and thus require easy to use physiological monitoring technologies in order to better monitor space crews for appropriate health management and successful space missions and space operations. Furthermore, the Space Technology Roadmap's Technology Area Breakdown Structure calls for improvements in research to support human health and performance (Technology Area 06). To address these needs, this project investigated a potential noncontact and noninvasive radio frequency-based technique of monitoring central hemodynamic function in human research subjects in response to orthostatic stress.

Description: No abstract available

Description: There continue to be important concerns about the possibility of the occurrence of acute radiation syndromes following nuclear and radiological terrorism or accidents that may result in mass casualties in densely populated areas. To guide medical personnel in their clinical decisions for effective medical management and treatment of the exposed individuals, biological markers are usually applied to examine radiation induced biological changes to assess the severity of radiation injury to sensitive organ systems. Among these the peripheral blood cell counts are widely used to assess the extent of radiation induced bone marrow injury. This is due to the fact that the hematopoietic system is the most vulnerable part of the human body to radiation damage. Particularly, the lymphocyte, granulocyte, and platelet cells are the most radiosensitive of the blood elements, and monitoring their changes after exposure is regarded as a practical and recommended laboratory test to estimate radiation dose and injury. Based upon years of physiological and pathophysiological investigation of mammalian hematopoietic systems, and rigorous coarse-grained bio-mathematical modeling and validation on species from mouse, to dog, monkey, and human, we have developed a set of software tools Hemodose, which can use single or serial granulocyte, lymphocyte, leukocyte, or platelet counts after exposure to estimate absorbed doses of adult victims very rapidly and accurately. Some patient data from historical accidents are utilized as examples to demonstrate the capabilities of these tools as a rapid point-of-care diagnostic or centralized high-throughput assay system in a large-scale radiological disaster scenario. Most significant to the improvement of national and local preparedness of a potential nuclear/radiological disaster, this HemoDose approach establishes robust correlations between the absorbed doses and victim's various types of blood cell counts not only in the early time window (1 or 2 days), but also in the very late phase (up to 4 weeks) after exposure.

Description: The effect that extended-duration space flights may have on human space travelers, including exploration missions, is widely discussed at the present time. Specifically, there is an increasing amount of evidence showing that the physical capacity of cosmonauts is significantly reduced after long-duration space flights. It is evident that the most impaired functions are those that rely on gravity, particularly up right posture and gait. Because of the sensorimotor disturbances manifested in the neurology of the posture and gait space flight and postflight changes may also be observed in debilitating motion sickness. While the severity of particular symptoms varies, disturbances in spatial orientation and alterations in the accuracy of voluntary movements are persistently observed after long-duration space flights. At this time most of the currently available data are primarily descriptive and not yet suitable for predicting operational impacts of most sensorimotor decrements observed upon landing on planetary surfaces or asteroids. In particular there are no existing data on the recovery dynamics or functionality of neurological, cardiovascular or muscle performance making it difficult to model or simulate the cosmonauts' activity after landing and develop the appropriate countermeasure that will ensure the rapid and safe recovery of crewmembers immediately after landing in what could be hostile environments. However and as a starting position, the videos we have acquired during recent data collection following the long duration flights of cosmonauts and astronauts walking and performing other tasks shortly after return from space flight speak volumes about their level of deconditioning. A joint Russian-American team has developed a new study specifically to address the changes in crewmembers performance and the recovery of performance with the intent of filling the missing data gaps. The first (pilot) phase of this study includes recording body kinematics and quantifying the coordination and timing of relatively simple basic movements - transition from seated and prone positions to standing, walking, stepping over obstacles, tandem walking, muscle compliance, as well as characteristics of postural sway and orthostatic tolerance. Testing for changes in these parameters have been initiated in the medical tent at the landing site. The first set of experiments showed that during the first hour after landing, cosmonauts and astronauts were able to execute (although slower and with more effort than preflight) simple movements such as egress from a seated or prone position and also to remain standing for 3.5 minutes without exhibiting pronounced cardiovascular changes. More challenging tests, however, demonstrated a prominent reduction in coordination - the obstacle task, for example, was performed at much slower speed and with a marked overestimation of the obstacle height and tandem walking was greatly degraded suggesting significant changes in proprioception, brainstem and vestibular function. There is some speculation that the neural changes, either from the bottom-up or top down may be long lasting; requiring compensatory responses that will modify or mask the adverse responses we have observed. Furthermore, these compensatory responses may actually be beneficial, helping achieve a more rapid adaptation to both weightlessness and a return to earth.

Description: High protein intake further increases bone resorption markers in head-down tilt bed rest (HDBR), most likely induced by low-grade metabolic acidosis. Adding an alkaline salt to a diet with high protein content prevents this additional rise of bone resorption markers in HDBR. In addition, high protein intake, specifically whey protein, increases muscle protein synthesis and improves glucose tolerance, which both are affected by HDBR. Resistive vibration exercise (RVE) training counteracts the inactivity-induced bone resorption during HDBR. To test the hypothesis that WP plus alkaline salt (KHCO3) together with RVE during HDBR will improve bone turnover markers, we conducted a randomized, three-campaign crossover design study with 12 healthy, moderately fit male subjects (age 34+/-8 y, body mass [BM] 70 +/- 8 kg). All study campaigns consisted of a 7-d ambulatory period, 21days of -6 deg. head-down tilt bed rest (HDBR), and a 6-d recovery period. Diet was standardized and identical across phases. In the control (CON) campaign, subjects received no supplement or RVE. In the intervention campaigns, subjects received either RVE alone or combined with WP and KHCO3 (NEX). WP was applied in 3 doses per day of 0.6 g WP/kg BM together with 6 doses of 15 mmol KHCO3 per day. Eleven subjects completed the RVE and CON campaign, 8 subjects completed all three campaigns. On day 21 of HDBR excretion of the bone resorption marker C-telopeptide (CTX) was 80+/-28% (p〈0.001) higher than baseline, serum calcium concentrations increased by 12 +/- 29% (p〈0.001) and serum osteocalcin concentrations decreased by 6+/-12% (p=0.001). Urinary CTX excretion was 11+/- 25% (p=0.02) lower on day 21 of HDBR in the RVE- and tended to decrease by 3+/- 22% (p=0.06) in the NEX campaign compared to CON. Urinary calcium excretion was higher on day 21 in HDBR in the RVE and NEX (24+/- 43% p=0.01; 25+/- 37% p=0.03) compared to the CON campaign. We conclude that combination of RVE with WP/KHCO3 was not superior to RVE alone in any of these results.

Description: In this work, we evaluate the differential effects of low- and high-LET radiation on 3-D organotypic cultures in order to investigate radiation quality impacts on gene expression and cellular responses. Reducing uncertainties in current risk models requires new knowledge on the fundamental differences in biological responses (the so-called radiation quality effects) triggered by heavy ion particle radiation versus low-LET radiation associated with Earth-based exposures. We are utilizing novel 3-D organotypic human tissue models that provide a format for study of human cells within a realistic tissue framework, thereby bridging the gap between 2-D monolayer culture and animal models for risk extrapolation to humans. To identify biological pathway signatures unique to heavy ion particle exposure, functional gene set enrichment analysis (GSEA) was used with whole transcriptome profiling. GSEA has been used extensively as a method to garner biological information in a variety of model systems but has not been commonly used to analyze radiation effects. It is a powerful approach for assessing the functional significance of radiation quality-dependent changes from datasets where the changes are subtle but broad, and where single gene based analysis using rankings of fold-change may not reveal important biological information. We identified 45 statistically significant gene sets at 0.05 q-value cutoff, including 14 gene sets common to gamma and titanium irradiation, 19 gene sets specific to gamma irradiation, and 12 titanium-specific gene sets. Common gene sets largely align with DNA damage, cell cycle, early immune response, and inflammatory cytokine pathway activation. The top gene set enriched for the gamma- and titanium-irradiated samples involved KRAS pathway activation and genes activated in TNF-treated cells, respectively. Another difference noted for the high-LET samples was an apparent enrichment in gene sets involved in cycle cycle/mitotic control. It is plausible that the enrichment in these particular pathways results from the complex DNA damage resulting from high-LET exposure where repair processes are not completed during the same time scale as the less complex damage resulting from low-LET radiation.

Description: Orthostatic intolerance affects 6080% of astronauts returning from longduration missions, representing a significant risk to completing missioncritical tasks. While likely multifactorial, a reduction in stroke volume (SV) represents one factor contributing to orthostatic intolerance during stand and head up tilt (HUT) tests. Current measures of SV during stand or HUT tests use Doppler ultrasound and require a trained operator and specialized equipment, restricting its use in the field. BeatScope (Finapres Medical Systems BV, The Netherlands) uses a modelflow algorithm to estimate SV from continuous blood pressure waveforms in supine subjects; however, evidence supporting the use of Modelflow to estimate SV in subjects completing stand or HUT tests remain scarce. Furthermore, because the blood pressure device is held extended at heart level during HUT tests, but allowed to rest at the side during stand tests, changes in the finger arterial pressure waveform resulting from arm positioning could alter modelflow estimated SV. The purpose of this project was to compare Doppler ultrasound and BeatScope estimations of SV to determine if BeatScope can be used during stand or HUT tests. Finger photoplethysmography was used to acquire arterial pressure waveforms corrected for hydrostatic fingertoheart height using the Finometer (FM) and Portapres (PP) arterial pressure devices in 10 subjects (5 men and 5 women) during a stand test while simultaneous estimates of SV were collected using Doppler ultrasound. Measures were made after 5 minutes of supine rest and while subjects stood for 5 minutes. Next, SV estimates were reacquired while each arm was independently raised to heart level, a position similar to tilt testing. Supine SV estimates were not significantly different between all three devices (FM: 68+/-20, PP: 71+/-21, US: 73+/-21 ml/beat). Upon standing, the change in SV estimated by FM (18+/-8 ml) was not different from PP (21+/-12), but both were significantly less than US (37+/-16 ml, p〈.05). Raising finger BP devices to heart level caused no significant change in SV measured with any of the devices (FM: 1.5+/-19, PP: 1.7+/-26, US: 0.5+/-6), although variability was 36x greater as assessed by both blood pressure devices compared to US. Retrospective analysis of blood pressure data to assess SV in 11 supine subjects revealed significantly different estimates between methods (FM: 95+/-17, US: 75+/-32, p〈.05), but the change in SV resulting from HUT was similar between methods (FM: 37+/-9, US: 40+/-18 ml). However, the correlation coefficient determined from pairs of SV estimated by US and FM was weak (r2=0.03). These data suggest Modelflow cannot be used in lieu of Doppler ultrasound to estimate SV during stand or HUT tests. Further investigation should focus on identifying factors contributing to differences between these measurement techniques in order to make use of a simple method for assessing beatbybeat changes in SV during postural changes, especially during field testing.

Description: In an effort to develop occupant protection standards for future multipurpose crew vehicles, the National Aeronautics and Space Administration (NASA) has looked to evaluate the test device for human occupant restraint with the modification kit (THORK) anthropomorphic test device (ATD) in relevant impact test scenarios. With the allowance and support of the National Highway Traffic Safety Administration, NASA has performed a series of sled impact tests on the latest developed THORK ATD. These tests were performed to match test conditions from human volunteer data previously collected by the U.S. Air Force. The objective of this study was to evaluate the THORK finite element (FE) model and the Total HUman Model for Safety (THUMS) FE model with respect to the tests performed. These models were evaluated in spinal and frontal impacts against kinematic and kinetic data recorded in ATD and human testing. Methods: The FE simulations were developed based on recorded pretest ATD/human position and sled acceleration pulses measured during testing. Predicted responses by both human and ATD models were compared to test data recorded under the same impact conditions. The kinematic responses of the models were quantitatively evaluated using the ISOmetric curve rating system. In addition, ATD injury criteria and human stress/strain data were calculated to evaluate the risk of injury predicted by the ATD and human model, respectively. Results: Preliminary results show wellcorrelated response between both FE models and their physical counterparts. In addition, predicted ATD injury criteria and human model stress/strain values are shown to positively relate. Kinematic comparison between human and ATD models indicates promising biofidelic response, although a slightly stiffer response is observed within the ATD. Conclusion: As a compliment to ATD testing, numerical simulation provides efficient means to assess vehicle safety throughout the design process and further improve the design of physical ATDs. The assessment of the THORK and THUMS FE models in a spaceflight testing condition is an essential first step to implementing these models in the computational evaluation of spacecraft occupant safety. Promising results suggest future use of these models in the aerospace field.

Description: Prolonged exposure to spaceflight conditions results in a battery of physiological changes, some of which contribute to sensorimotor and neurovestibular deficits. Upon return to Earth, functional performance changes are tested using the Functional Task Test (FTT), which includes an obstacle course to observe postflight balance and postural stability, specifically during turning. The goal of this study was to quantify changes in movement strategies during turning events by observing the latency between headandtrunk coordinated movements. It was hypothesized that subjects experiencing neurovestibular adaptations would exhibit headtotrunk locking ('en bloc' movement) during turning, exhibited by a decrease in latency between head and trunk movement. FTT data samples were collected from ISS missions. Samples were analyzed three times preexposure, immediately postexposure (1 day post) and 2to3 times during recovery from the microgravity environment. Two 3D inertial measurements units (XSens MTx) were attached to subjects, one on the head and one on the upper back. This study focused primarily on the yaw movements about the subject's center of rotation. Time differences (latency) between head and trunk movement were calculated at two points on the obstacle course: the first turn to enter the obstacle course (approximately 90 turn) and averaged across a slalom obstacle portion, consisting of three turns (approximately three 90 turns). Preliminary analysis of the data shows a trend toward decreasing headtotrunk movement latency during postflight ambulation in slalom turning after reintroduction to Earth gravity in ISS astronauts. It is clear that changes in movement strategies are adopted during exposure to the microgravity environment and upon reintroduction to a gravity environment. Most ISS subjects exhibit symptoms of neurovestibular changes ('en bloc head and trunk movement) which may impact their ability to perform postflight functional tasks.

Description: 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. 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 damage and inflammation can accelerate the development of atherosclerosis. PURPOSE The purpose of this investigation is to determine whether biomarkers of oxidative and inflammatory stress are elevated during and after long-duration spaceflight and investigate if a relation exists between levels of these biomarkers and structural and functional indices of atherosclerotic risk measured in the carotid and brachial arteries. This is the first study to propose assessing atherosclerotic risk using biochemical, structural, and functional measures before, during, and immediately after spaceflight, and structural and functional measures for up to 5 years after landing. METHODS We will study 12 astronauts before, during, and up to 5 years after long-duration ISS missions. A panel of biomarkers of oxidative and inflammatory stress will be measured twice before flight, early (flight days 15 and 60) and late (2 weeks before landing) during the mission, and early in the postflight recovery phase (approx 3 days after landing). Arterial structure and vascular compliance will be measured at the same times and also at 1, 3, and 5 years after landing (surveillance). Arterial function will be measured using the same preflight, postflight, and surveillance schedule as arterial structure and vascular compliance measures, but will not be measured inflight. Biomarkers, some of which we have previously shown to be elevated with spaceflight, will be measured in venous blood samples and 24-h (in-flight) and 48-h (pre- and post-flight) urine pools. Arterial structure will be assessed from measures of carotid intima-media thickness, which have been shown to be better indicators of atherosclerotic than the Framingham Risk Score. Arterial function will be assessed using brachial flow-mediated dilation, a well-validated measure used to assess endothelium-dependent vasodilation and is a sensitive predictor of atherosclerotic risk. Arterial pulse pressure measured in the brachial artery and stroke volume measured from cardiac ultrasound will be used to assess hemodynamic status, cardiac function, and systemic vascular compliance. Three astronauts are actively participating in the preflight data collection and training activities. One astronaut has completed all preflight activities and will participate in the first in-flight data collection sessions by the end of 2013. The first post-flight data collection sessions will occur in the spring of 2014. EXPECTED RESULTS We hypothesize that biomarkers of oxidative and inflammatory stress will increased with spaceflight and will correlate with increased carotid intima-media thickness during and after flight and with decreased flow-mediated dilation after the mission. Furthermore, we hypothesize that measures of oxidative stress will return to baseline after flight, but biomarkers of inflammatory stress and vascular indices of atherosclerotic risk will remain elevated.

Description: Liver function, especially the rate of metabolic enzyme activities, determines the concentration of circulating drugs and the duration of their efficacy. Most pharmaceuticals are metabolized by the liver, and clinically-used medication doses are given with normal liver function in mind. A drug overdose can result in the case of a liver that is damaged and removing pharmaceuticals from the circulation at a rate slower than normal. Alternatively, if liver function is elevated and removing drugs from the system more quickly than usual, it would be as if too little drug had been given for effective treatment. Because of the importance of the liver in drug metabolism, we want to understand any effects of spaceflight on the enzymes of the liver. Dietary factors and exposure to radiation are aspects of spaceflight that are potential oxidative stressors and both can be modeled in ground experiments. In this experiment, we examined the effects of high dietary iron and low dose gamma radiation (individually and combined) on the gene expression of enzymes involved in drug metabolism, redox homeostasis, and DNA repair. METHODS All procedures were approved by the JSC Animal Care and Use Committee. Male Sprague-Dawley rats were divided into 4 groups (n=8); control, high Fe diet (650 mg iron/kg), radiation (fractionated 3 Gy exposure from a Cs- 137 source) and combined high Fe diet + radiation exposure. Animals were euthanized 24h after the last treatment of radiation; livers were removed immediately and flash -frozen in liquid nitrogen. Expression of genes thought to be involved in redox homeostasis, drug metabolism and DNA damage repair was measured by RT-qPCR. Where possible, protein expression of the same genes was measured by western blotting. All data are expressed as % change in expression normalized to reference gene expression; comparisons were then made of each treatment group to the sham exposed/ normal diet control group. Data was considered significant at p〈 0.5. RESULTS Among the redox homeostasis genes examined, metallothionein showed a significant down regulation in the radiation treated group (-3.85 fold) and a trend toward down regulation in the high Fe + rad group. Metallothionein is involved in the regulation of physiological metals and also has antioxidant activities. Among the drug metabolism genes examined, ATP binding cassette subfamily B (Abcb1b) gene expression increased more than 10-fold in both groups that received radiation treatments. This increased expression was also seen at the protein level. This ABC transporter carries many different compounds across cell membranes, including administered medications. The cytochrome P450 2E1 enzyme, a mixed-function oxidase that deactivates some medications and activates others, showed about a 2-fold increase in gene expression in both radiation-treated groups, with a trend toward increased expression at the protein level. Expression of epoxide hydrolase, which detoxifies polycyclic aromatic hydrocarbons, showed similar 2-fold increases. Among the DNA repair genes examined, expression of RAD51 was significantly down regulated (1.5 fold) in the radiation treated group. RAD51 is involved in repair of double-stranded DNA breaks. CONCLUSION This experiment used 2 different sources of physiological oxidative stress, administered separately and together, and examined their impacts on liver gene and protein expression. It is clear that significant changes occurred in expression of several genes and proteins in the radiation-treated animals. If the results from this ground analog of portions of the spaceflight environment hold true for the spaceflight environment itself, the physiological roles of the affected enzymes (drug transport and metabolism, redox homeostasis) could mean consequences in redox homeostasis or the pharmacokinetics of administered medications

Description: Brain derived neurotrophic factor (BDNF) is the main activity-dependent neurotrophin in the human nervous system. BDNF is implicated in production of new neurons from dentate gyrus stem cells (hippocampal neurogenesis), synapse formation, sprouting of new axons, growth of new axons, sprouting of new dendrites, and neuron survival. Alterations in the amount or activity of BDNF can produce significant detrimental changes to cortical function and synaptic transmission in the human brain. This can result in glial and neuronal dysfunction, which may contribute to a range of clinical conditions, spanning a number of learning, behavioral, and neurological disorders. There is an extensive body of work surrounding the BDNF molecular network, including BDNF gene polymorphisms, methylated BDNF gene promoters, multiple gene transcripts, varied BDNF functional proteins, and different BDNF receptors (whose activation differentially drive the neuron to neurogenesis or apoptosis). BDNF is also closely linked to mitochondrial biogenesis through PGC-1alpha, which can influence brain and muscle metabolic efficiency. BDNF AS A HUMAN SPACE FLIGHT COUNTERMEASURE TARGET Earth-based studies reveal that BDNF is negatively impacted by many of the conditions encountered in the space environment, including oxidative stress, radiation, psychological stressors, sleep deprivation, and many others. A growing body of work suggests that the BDNF network is responsive to a range of diet, nutrition, exercise, drug, and other types of influences. This section explores the BDNF network in the context of 1) protecting the brain and nervous system in the space environment, 2) optimizing neurobehavioral performance in space, and 3) reducing the residual effects of space flight on the nervous system on return to Earth

Description: Prior to 2010, several ISS crewmembers returned from spaceflight with changes to their vision, ranging from a mild hyperopic shift to frank disc edema. As a result, NASA expanded clinical vision testing to include more comprehensive medical imaging, including Optical Coherence Tomography and 3 Tesla Brain and Orbit MRIs. The Space and Clinical Operations (SCO) Division developed a clinical practice guideline that classified individuals based on their symptoms and diagnoses to facilitate clinical care. For the purposes of clinical surveillance, this classification was applied retrospectively to all crewmembers who had sufficient testing for classification. This classification is also a tool that has been leveraged for researchers to identify potential risk factors. In March 2014, driven in part by a more comprehensive understanding of the imaging data and increased imaging capability on orbit, the SCO Division revised their clinical care guidance to outline inflight care and increase postflight follow up. The new clinical guidance does not include a classification scheme

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

Description: Ongoing collaborative research efforts between NASA's Neuroscience and Cardiovascular Laboratories, and the Institute of Biomedical Problems' (IBMP) Sensory-Motor and Countermeasures Laboratories have been measuring functional sensorimotor, cardiovascular and strength responses following bed rest, dry immersion, short-duration (Space Shuttle) and long-duration (Mir and International Space Station [ISS]) space flights. While the unloading paradigms associated with dry immersion and bed rest does serve as acceptable flight analogs, testing of crew responses following the long-duration flights previously has not been possible until a minimum of 24 hours after landing. As a result, it is not possible to estimate the nonlinear trend of the early (〈24 hours) recovery process nor is it possible to accurately assess the full impact of the decrements associated with long-duration flight. To overcome these limitations, both the Russian and U.S. programs have implemented testing at the landing site. By joint agreement, this research effort has been identified as the functional Field Test (FT). For practical reasons the FT has been divided into two phases: the full FT and a preliminary pilot version (PFT) of the FT that is reduced in both length and scope. The primary goal of this research is to determine functional abilities in long-duration space-flight crews beginning as soon after landing as possible (〈 2 hours) with one to three immediate follow-up measurements on the day of landing. This goal has both sensorimotor and cardiovascular elements, including evaluations of NASA's new anti-orthostatic compression garment and the Russian Kentavr garment. Functional sensorimotor measurements will include, but are not limited to, assessing hand/eye coordination, egressing from a seated position, walking normally without falling, measuring of dynamic visual acuity, discriminating different forces generated with both the hands and legs, recovering from a fall, coordinated walking involving tandem heel-to-toe placement, and determining postural ataxia while standing. The cardiovascular portion of the investigation includes measuring blood pressure and heart rate during a timed stand test in conjunction with postural ataxia testing (quiet stance sway) as well as cardiovascular responses during the other functional tasks. In addition to the immediate post-landing collection of data for the full FT, postflight data will be acquired between one and three more other times within the 24 hours after landing and will continue over the subsequent weeks until functional sensorimotor and cardiovascular responses have returned to preflight normative values. The PFT represents a single trial run comprised of a jointly agreed upon subset of tests from the full FT and relies heavily on IBMP's Sensory-Motor and Countermeasures Laboratories for content and implementation. The PFT has been collected on several ISS missions. Testing included: (1) a sit-to-stand test, (2) recovery from a fall where the crewmember began in the prone position on the ground and then stood for 3 minutes while cardiovascular stability was determined and postural ataxia data were acquired, and (3) a tandem heel-totoe walk test to determine changes in the central locomotor program. Video, cardiovascular parameters (heart rate and blood pressure), data from body-worn inertial sensors, and severity of postflight motion sickness were collected for each test session. In summary, the level of functional deficit is expected to be most profound during the acquisition of gravity loads immediately after landing when the demands for crew intervention in response to emergency operations will be greatest. Clearly measureable performance parameters such as ability to perform a seat egress, recover from a fall or the ability to see clearly when walking, and related physiologic data (orthostatic responses) are required to provide an evidence base for characterizing programmatic risks and the degree of variability among crewmembers for exploration missions where the crew will be unassisted after landing. Overall, these early functional and related physiologic measurements will allow estimation of nonlinear sensorimotor and cardiovascular recovery trends that has not been previously captured in over 50 years of space flight.

Description: This joint 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 project specifically addresses the sensorimotor research gap "What are the changes in sensorimotor function over the course of a mission?" Six ISS crewmembers will be requested to participate in three preflight sessions (between 120 and 60 days prior to launch) and then three postflight sessions on R+0/1 day, R+4 +/-2 days, and R+8 +/-2 days. The three specific aims include: (a) fixation of actual and imagined target locations at different distances; (b) directed eye and arm movements along different spatial reference frames; and (c) the vestibulo-ocular reflex during translation motion with fixation targets at different distances. These measures will be compared between upright and tilted conditions. Measures will then be compared with and without a vibrotactile sensory aid that indicates how far one has tilted relative to the straight-ahead direction. The flight study was been approved by the medical review boards and will be implemented in the upcoming Informed Crew Briefings to solicit flight subject participation. Preliminary data has been recorded on 6 subjects during parabolic flight to examine the spatial coding of eye movements during roll tilt relative to perceived orientations while free-floating during the microgravity phase of parabolic flight or during head tilt in normal gravity. Binocular videographic recordings obtained in darkness allowed us to quantify the mean deviations in gaze trajectories along both horizontal and vertical coordinates relative to the aircraft and head orientations. During some parabolas, a vibrotactile sensory aid provided feedback of body orientation relative to the plane coordinates. RESULTS Both variability and curvature of gaze trajectories increased during roll tilt compared to the upright position. The saccades were less accurate during parabolic flight compared to measurements obtained in normal gravity. Although subjects were instructed to look off in the distance while performing the eye movements, fixation distance varied with vertical gaze direction independent of whether the saccades were made along perceived aircraft or head orientations. The increased errors in gaze trajectories along both perceived orientations during microgravity can be attributed to the otolith's role in spatial coding of eye movements. 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 vestibular loss patients and the elderly to mitigate risks due to loss of orientation.

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

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

Description: There is considerable variability among astronauts with respect to changes in maximal aerobic capacity (VO2peak) during International Space Station (ISS) missions, ranging from a 5% increase to 30% decline. Individual differences may be due to in-flight aerobic exercise time and intensity. PURPOSE: To evaluate the effects of in-flight aerobic exercise time and intensity on change in VO2peak during ISS missions. METHODS: Astronauts (N=11) performed peak cycle tests approx 60 days before flight (L-60), on flight day (FD) approx 14, and every approx 30 days thereafter. Metabolic gas analysis and heart rate (HR) were measured continuously during the test using the portable pulmonary function system. HR and duration of each in-flight cycle ergometer and treadmill (TM) session were recorded and averaged in time segments corresponding to each peak test. Mixed effects linear regression with exercise mode (TM or cycle) as a categorical variable was used to assess the contributions of exercise intensity (%time 〉70% peak HR or %time 〉90% peak HR) and time (min/wk), adjusted for body weight, on %change in VO2peak during the mission, and incorporating the repeated-measures experimental design. RESULTS: 110 observations were included in the model (4-6 peak cycle tests per astronaut, 2 exercise devices). VO2peak was reduced from preflight throughout the mission (FD14: 13+/-13% and FD 105: 8+/-10%). Exercise intensity (%peak HR: FD14=66+/-14; FD105=75+/-8) and time (min/wk: FD14=82+/-46; FD105=158+/-40) increased during flight. The models showed main effects for exercise time and intensity with no interactions between time, intensity, and device (70% peak HR: time [z-score=2.39; P=0.017], intensity [z-score=3.51; P=0.000]; 90% peak HR: time [zscore= 3.31; P=0.001], intensity [z-score=2.24; P=0.025]). CONCLUSION: Exercise time and intensity independently contribute to %change in VO2peak during ISS missions, indicating that there are minimal values for exercise time and intensity required to maintain VO2peak. As the FD105 average exercise intensity and time did not prevent a decline in VO2peak from preflight, astronauts' exercise prescriptions should target at least 160 min of weekly aerobic exercise at an average above 75% peak HR with increased time at intensities above 90% of peak HR starting early in the mission.

Description: Aerobic capacity (VO2peak) previously has not been measured during or after long-duration spaceflight. PURPOSE: To measure VO2peak and submaximal exercise responses during and after International Space Station (ISS) missions. METHODS: Astronauts (9 M, 5 F: 49 +/- 5 yr, 175 +/- 7 cm, 77.2 +/- 15.1 kg, 40.6 +/- 6.4 mL/kg/min [mean +/-SD]) performed graded peak cycle tests ~90 days before spaceflight, 15 d (FD15) after launch and every ~30 d thereafter during flight, and 1 (R+1), 10 (R+10), and 30 d (R+30) after landing. Oxygen consumption (VO2) and heart rate (HR) were measured from rest to peak exercise, while cardiac output (Q), stroke volume (SV), and arterial-venous oxygen difference (a-vO2diff) were measured only during rest and submaximal exercise. Data were analyzed using mixed-model linear regression. Body mass contributed significantly to statistical models, and thus results are reported as modeled estimates for an average subject. RESULTS: Early inflight (FD15) VO2peak was 17% lower (95% CI = - 22%, -13%) than preflight. VO2peak increased during spaceflight (0.001 L/min/d, P = 0.02) but did not return to preflight levels. On R+1 VO2peak was 15% (95% CI = -19%, -10%) lower than preflight but recovered to within 2% of preflight by R+30 (95% CI = -6%, +3%). Peak HR was not significantly different from preflight at any time. Inflight submaximal VO2 and a-vO2diff were generally lower than preflight, but the Q vs. VO2 slope was unchanged. In contrast, the SV vs. VO2 slope was lower (P 〈 0.001), primarily due to elevated SV at rest, and the HR vs. VO2 slope was greater (P 〈 0.001), largely due to elevated HR during more intense exercise. On R+1 although the relationships between VO2 and Q, SV, and HR were not statistically different than preflight, resting and submaximal exercise SV was lower (P 〈 0.001), resting and submaximal exercise HR was higher (P 〈 0.002), and a-vO2diff was unchanged. HR and SV returned to preflight levels by R+30. CONCLUSION: In the average astronaut VO2peak was reduced during spaceflight and immediately after landing but factors contributing to lower VO2peak may be different during spaceflight and recovery. Maintaining Q while VO2 is reduced inflight may be suggestive of an elevated blood flow to vascular beds other than exercising muscles, but decreased SV after flight likely reduces Q at peak exertion.

Description: Spaceflight reduces aerobic capacity and may be linked with maladaptations in the O2 transport pathway. The aim was to 1) evaluate the cardiorespiratory adaptations following 6 months aboard the International Space Station and 2) model the contributions of convective (Q (raised dot) O2) and peripheral diffusive (DO2) components of O2 transport to changes in peak O2 uptake (V (raised dot) O2PEAK). To date, 1 male astronaut (XX yrs) completed an incremental exercise test to measure V (raised dot) O2PEAK prior to and 2 days post-flight. Cardiac output (Q (raised dot) ) was measured at three submaximal work rates via carbon dioxide rebreathing. The Q (raised dot) :V (raised dot) O2 relationship was extrapolated to V (raised dot) O2PEAK to determine Q (raised dot) PEAK. Hemoglobin concentration was measured at rest via a venous blood sample. These measurements were used to model the changes in Q (raised dot) O2 and DO2 using Fick's principle of mass conservation and Law of Diffusion as established by Wagner and colleagues (Annu. Rev. Physiol 58: 21-50, 1996 and J. Appl. Physiol. 73: 1067-1076, 1992). V (raised dot) O2PEAK decreased postflight from 3.72 to 3.45 l min-1, but Q (raised dot) PEAK increased from 24.5 to 27.7 l min-1. The decrease in V (raised dot) O2PEAK post-flight was associated with a 21.2% decrease in DO2, an 18.6% decrease in O2 extraction, but a 3.4% increase in Q (raised dot) O2. These preliminary data suggest that long-duration spaceflight reduces peripheral diffusing capacity and that it largely contributes to the post-flight decrease in aerobic capacity.

Description: The One Year Mission (1YM) by two astronauts on the International Space Station (ISS), starting in March 2015, offers a unique opportunity to expand multilateral collaboration by sharing data and resources among the partner agencies in preparation for planned space exploration missions beyond low Earth orbit. Agreements and protocols will be established for the collection, distribution, analysis and reporting of both research and clinical data. Data will be shared between the agencies sponsoring the investigators, and between the research and clinical medicine communities where common interests are identified. The assignment of only two astronauts, one Russian and the other American, to the 1YM necessitated creativity in bilateral efforts to maximize the biomedical return from the opportunity. Addition of Canadian, European and Japanese investigations make the effort even more integrative. There will be three types of investigations: joint, crossparticipation and dataexchange. The joint investigations have US and Russian coprincipal investigators, and the data acquired will be their common responsibility. The other two types must develop data sharing agreements and processes specific to their needs. A multilateral panel of ISS partner space agencies will develop policies for international exchange of scientific information to meet their science objectives and priorities. They will promote archiving of space flight data and will inform each other and the scientific community at large about the results obtained from space life sciences studies. Integration tasks for the 1YM are based on current experience from the ISS and previous efforts on the Russian space station Mir. Closer coordination between international partners requires more common approaches to remove barriers to multilateral resource utilization on the ISS. Greater integration in implementation should increase utilization efficiency to benefit all participants in spaceflight human research. This presentation will describe the overarching principles for multilateral data collection, analysis and sharing and for data security for medical and research data shared between ISS partners prior to release in public forums.

Description: The bisphosphonate study is a collaborative effort between the NASA and JAXA space agencies to investigate the potential for antiresorptive drugs to mitigate bone changes associated with long-duration spaceflight. Elevated bone resorption is a hallmark of human spaceflight and bed rest (common zero-G analog). We tested whether an antiresorptive drug in combination with in-flight exercise would ameliorate bone loss and hypercalcuria during longduration spaceflight. Measurements include DXA, QCT, pQCT, and urine and blood biomarkers. We have completed analysis of 7 crewmembers treated with alendronate during flight and the immediate postflight (R+〈2 week) data collection in 5 of 10 controls without treatment. Both groups used the advanced resistive exercise device (ARED) during their missions. We previously reported the pre/postflight results of crew taking alendronate during flight (Osteoporosis Int. 24:2105-2114, 2013). The purpose of this report is to present the 12-month follow-up data in the treated astronauts and to compare these results with preliminary data from untreated crewmembers exercising with ARED (ARED control) or without ARED (Pre-ARED control). Results: the table presents DXA and QCT BMD expressed as percentage change from preflight in the control astronauts (18 Pre-ARED and the current 5 ARED-1-year data not yet available) and the 7 treated subjects. As shown previously the combination of exercise plus antiresorptive is effective in preventing bone loss during flight. Bone measures for treated subjects, 1 year after return from space remain at or near baseline values. Except in one region, the treated group maintained or gained bone 1 year after flight. Biomarker data are not currently available for either control group and therefore not presented. However, data from other studies with or without ARED show elevated bone resorption and urinary Ca excretion while bisphosphonate treated subjects show decreases during flight. Comparing the two control groups suggests significant but incomplete improvement in maintaining BMD using the newer exercise protocols compared to earlier resistive exercise protocols. Quantitative characterization of this improvement requires additional measurements in the ARED control group that we are currently collecting. In conclusion, these results indicate that an antiresorptive may be an effective adjunct to exercise during long-duration spaceflight.

Description: There are no specific guidelines for the management of renal stones in astronauts. Given the increased risk for bone loss, hypercalcuria, and stone formation due to microgravity, a clinical practice guideline is needed. Methods An extensive review of the literature and current aeromedical standards for the management of renal stones was done. The NASA Flight Medicine Clinic's electronic medical record and Longitudinal Survey of Astronaut Health were also reviewed. This information was used to create an algorithm for the management of renal stones in astronauts. Results Guidelines are proposed based on accepted standards of care, with consideration to the environment of spaceflight. In a usual medical setting, asymptomatic, small stones less than 7 mm are often observed over time. Given the constraints of schedule, and the risks to crew health and mission, this approach is too liberal. An upper limit of 3 mm stone diameter was adopted before requiring intervention, because this is the largest size that has a significant chance of spontaneous passage on its own. Other specific guidelines were also created. Discussion The spaceflight environment requires more aggressive treatment than would otherwise be found with the usual practice of medicine. A small stone can become a major problem because it may ultimately require medical evacuation from orbit. Thus renal stones are a significant mission threat and should be managed in a systematic way to mitigate risks to crew health and mission success.

Description: The NASA Human Research Program's (HRP) Behavioral Health and Performance Element (BHP) supports and conducts research to mitigate deleterious outcomes related to fatigue, sleep loss, circadian desynchronization, and work overload. Objective evidence indicates that within the context of the International Space Station (ISS), sleep is reduced and there is circadian misalignment. Despite chronic sleep loss and high workloads; however, astronauts successfully complete their missions. Contributing to their success is not only the tremendous skills and capabilities of each astronaut, but also the collaborative team efforts amongst the crew, between flight and ground crews, and through realtime care provided by medical personnel. It is anticipated that risks to human health and performance will increase in the context of exploration missions, where crewmembers will venture to deep space for extended durations and in small vehicles with limited communication with home. Hence, fatiguerelated countermeasures are being developed and/or validated that include unobtrusive monitoring technologies to detect fatiguerelated performance decrements, environmental countermeasures, and sleep education and training for flight and ground crews. Given that fatigue is an issue in current ISS missions, the BHP works collaboratively with Space Medicine operations to collect data in the operational environment, to validate fatigue-related countermeasures, and provide evidencebased mitigations. Our presentation will summarize fatiguerelated operational research that is underway through NASA's BHP in partnership with its operational counterparts. Efforts include studies evaluating the effects of hypnotics, lighting protocols as countermeasures for circadian entrainment, and investigations involving education and training. This presentation will further identify, based on flight and terrestrial evidence, additional sleep and circadian countermeasures that may still be needed to support exploration missions. Lessons learned from transitioning research deliverables into ISS operations will also be discussed.

Description: No abstract available

Description: No abstract available

Description: Astronauts experience a profound sensorimotor adaptation during transition to and from the microgravity environment of space. With the upcoming shift to extralong duration missions (upwards of 1 year) aboard the International Space Station, the immediate risks to astronauts during these transitory periods become more important than ever to understand and prepare for. Recent advances in virtual reality technology enable everyday adoption of these tools for entertainment and use in training. Embedding an individual in a virtual environment (VE) allows the ability to change the perception of visual flow, elicit automatic motor behavior and produce sensorimotor adaptation, not unlike those required during long duration microgravity exposure. The overall goal of this study is to determine the feasibility of present head mounted display technology (HMD) to produce reliable visual flow information and the expected adaptation associated with virtual environment manipulation to be used in future sensorimotor adaptability countermeasures. To further understand the influence of visual flow on gait adaptation during treadmill walking, a series of discordant visual flow manipulations in a virtual environment are proposed. Six healthy participants (3 male and 3 female) will observe visual flow information via HMD (Oculus Rift DK2) while walking on an instrumented treadmill at their preferred walking speed. Participants will be immersed in a series of VE's resembling infinite hallways with different visual characteristics: an office hallway, a hallway with pillars and the hallway of a fictional spacecraft. Participants will perform three trials of 10 min. each, which include walking on the treadmill while receiving congruent or incongruent visual information via the HMD. In the first trial, participants will experience congruent visual information (baseline) where the hallway is perceived to move at the same rate as their walking speed. The final two trials will be randomized among participants where the hallway is perceived to move at either half (0.5x) or twice (2.0x) their preferred walking speed. Participants will remain on the treadmill between trials and will not be warned of the upcoming change to visual flow to minimize preparatory adjustments. Stride length, step frequency and dualsupport time will be quantified during each trial. We hypothesize that participants will experience a rapid modification in gait performance during periods of adaptive change, expressed as a decrease in step length, an increase in step frequency and an increase in dualsupport time, followed by a period of adaptation where these movement parameters will return to nearbaseline levels. As stride length, step frequency and dual support times return to baseline values, an adaptation time constant will be derived to establish individual timetoadapt (TTA). HMD technology represents a paradigm shift in sensorimotor adaptation training where gait adaptability can be stressed using offtheshelf consumer products and minimal experimental equipment, allowing for greater training flexibility in astronaut and terrestrial applications alike.

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

Description: Spaceflight-induced bone loss is associated with increased bone resorption (1, 2), and either unchanged or decreased rates of bone formation. Resistive exercise had been proposed as a countermeasure, and data from bed rest supported this concept (3). An interim resistive exercise device (iRED) was flown for early ISS crews. Unfortunately, the iRED provided no greater bone protection than on missions where only aerobic and muscular endurance exercises were available (4, 5). In 2008, the Advanced Resistive Exercise Device (ARED), a more robust device with much greater resistance capability, (6, 7) was launched to the ISS. Astronauts who had access to ARED, coupled with adequate energy intake and vitamin D status, returned from ISS missions with bone mineral densities virtually unchanged from preflight (7). Bone biochemical markers showed that while the resistive exercise and adequate energy consumption did not mitigate the increased bone resorption, bone formation was increased (7, 8). The typical drop in circulating parathyroid hormone did not occur in ARED crewmembers. In 2014, an updated look at the densitometry data was published. This study confirmed the initial findings with a much larger set of data. In 42 astronauts (33 male, 9 female), the bone mineral density response to flight was the same for men and women (9), and those with access to the ARED did not have the typical decrease in bone mineral density that was observed in early ISS crewmembers with access to the iRED (Figure 1) (7). Biochemical markers of bone formation and resorption responded similarly in men and women. These data are encouraging, and represent the first in-flight evidence in the history of human space flight that diet and exercise can maintain bone mineral density on long-duration missions. However, the maintenance of bone mineral density through bone remodeling, that is, increases in both resorption and formation, may yield a bone with strength characteristics different from those that existed before space flight. Studies to assess bone strength after flight are underway at NASA, to better understand the results of bone remodeling. Studies are also underway to evaluate optimized exercise protocols and nutritional countermeasures. Regardless, there is clear evidence of progress being made to protect bone during spaceflight.

Description: As mission distance and duration increase, the need grows for noninvasive disease prevention and immunomodulation, especially given the limited medical response capability expected for these missions and the immune dysregulation documented in crew. Additionally, changes in diet, lifestyle, antibiotic usage, and the environmental stresses during spaceflight may alter crewmembers' intestinal microbiome. The addition of probiotic bacteria to the space food system is expected to confer immunostimulatory benefits on crewmembers, with the potential to counteract the immune dysregulation that has been documented in spaceflight. Based on previous studies that demonstrated unique microbiological responses to the low shear environment of spaceflight, probiotic organisms hold the potential to induce enhanced beneficial responses through mechanisms, such as beneficial interactions with human immune cells and repression of colonization of pathogens on the mucosa. The work presented here will begin to address two research gaps related to providing probiotics in spaceflight: 1) delivery, and 2) the effect of the low shear microgravity environment on probiotic attributes. The probiotic Lactobacillus acidophilus was selected for investigation due to its wide commercial use and documented benefits that include inhibition of virulence related gene expression in pathogens and mucosal stimulation of immune cells. The delivery system for probiotics has not been determined for spaceflight, where the food system is shelf stable and the lack of refrigeration prevents the use of traditional dairy delivery methods. In order to demonstrate the potential of the space food system to deliver viable probiotic bacteria to crewmembers, the probiotic L. acidophilus was packaged in high barrier flight packaging in nonfat dry milk (NFDM) or retained in commercial capsule form. Viable cells were enumerated over 8 months of storage at 22, 4, and 80C. The survival of L. acidophilus rehydrated in NFDM, in a PBS control, and directly from the capsule was also evaluated following stress challenge with simulated gastric and intestinal juices to determine the method that would deliver the most viable cells to the intestine, where they would be expected to confer beneficial effects. L. acidophilus was found to be stable to gastric and intestinal juice challenge when delivered in rehydrated NFDM, even after two hours of exposure. In comparison, L. acidophilus was reduced by 15 logs when exposed to gastric and intestinal juice directly and when rehydrated in a PBS control. Shelf life data indicated that L. acidophilus would require refrigerated or frozen storage to remain viable at adequate levels over the multiyear storage periods required for spaceflight. This study suggests that the protective effect provided by the dairy matrix, and not merely rehydration prior to consumption, extends probiotic viability and stress tolerance during storage in spaceflight and in simulated digestion conditions more adequately than a capsule. In addition to effective delivery, it is essential to understand the microgravity effects on the stress tolerances and genetic expression of probiotic bacteria to enable optimization of growth, survival, strain selection, and conferred benefits in spaceflight. In our current study, groundbased characterization of the growth, stress response, and transcriptomic response of L. acidophilus will be accomplished using the low shear modeled microgravity (LSMMG) culture environment in the rotating wall vessel (RWV). We hypothesize that L. acidophilus will maintain or improve its growth and stress response following culture in the LSMMG environment, and that transcriptomic analysis will define the associated molecular mechanism(s), resulting in the ability to optimize strain selection.

Description: Visual assessment of exercise form on the Advanced Resistive Exercise Device (ARED) on orbit is difficult due to the motion of the entire device on its Vibration Isolation System (VIS). The VIS allows for two degrees of device translational motion, and one degree of rotational motion. In order to minimize the forces that the VIS must damp in these planes of motion, the floor of the ARED moves as well during exercise to reduce changes in the center of mass of the system. To help trainers and other exercise personnel better assess squat and deadlift form a tool was developed that removes the VIS motion and creates a stick figure video of the exerciser. Another goal of the study was to determine whether any useful kinematic information could be obtained from just a single camera. Finally, the use of these data may aid in the interpretation of QCT hip structure data in response to ARED exercises performed in-flight. After obtaining informed consent, four International Space Station (ISS) crewmembers participated in this investigation. Exercise was videotaped using a single camera positioned to view the side of the crewmember during exercise on the ARED. One crewmember wore reflective tape on the toe, heel, ankle, knee, hip, and shoulder joints. This technique was not available for the other three crewmembers, so joint locations were assessed and digitized frame-by-frame by lab personnel. A custom Matlab program was used to assign two-dimensional coordinates to the joint locations throughout exercise. A second custom Matlab program was used to scale the data, calculate joint angles, estimate the foot center of pressure (COP), approximate normal and shear loads, and to create the VIS motion-corrected stick figure videos. Kinematics for the squat and deadlift vary considerably for the four crewmembers in this investigation. Some have very shallow knee and hip angles, and others have quite large ranges of motion at these joints. Joint angle analysis showed that crewmembers do not return to a normal upright stance during squat, but remain somewhat bent at the hips. COP excursions were quite large during these exercises covering the entire length of the base of support in most cases. Anterior-posterior shear was very pronounced at the bottom of the squat and deadlift correlating with a COP shift to the toes at this part of the exercise. The stick figure videos showing a feet fixed reference frame have made it visually much easier for exercise personnel and trainers to assess exercise kinematics. Not returning to fully upright, hips extended position during squat exercises could have implications for the amount of load that is transmitted axially along the skeleton. The estimated shear loads observed in these crewmembers, along with a concomitant reduction in normal force, may also affect bone loading. The increased shear is likely due to the surprisingly large deviations in COP. Since the footplate on ARED moves along an arced path, much of the squat and deadlift movement is occurring on a tilted foot surface. This leads to COP movements away from the heel. The combination of observed kinematics and estimated kinetics make squat and deadlift exercises on the ARED distinctly different from their ground-based counterparts. CONCLUSION This investigation showed that some useful exercise information can be obtained at low cost, using a single video camera that is readily available on ISS. Squat and deadlift kinematics on the ISS ARED differ from ground-based ARED exercise. The amount of COP shift during these exercises sometimes approaches the limit of stability leading to modifications in the kinematics. The COP movement and altered kinematics likely reduce the bone loading experienced during these exercises. Further, the stick figure videos may prove to be a useful tool in assisting trainers to identify exercise form and make suggestions for improvements

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

Description: Crewmember adapted to the microgravity state may need to egress the vehicle within a few minutes for safety and operational reasons after gravitational transitions. The transition from one sensorimotor state to another consists of two main mechanisms: strategic and plastic-adaptive and have been demonstrated in astronauts returning after long duration space flight. Strategic modifications represent "early adaptation" - immediate and transitory changes in control that are employed to deal with short-term changes in the environment. If these modifications are prolonged then plastic-adaptive changes are evoked that modify central nervous system function, automating new behavioral responses. More importantly, this longer term adaptive recovery mechanism was significantly associated with their strategic ability to recover on the first day after return to Earth G. We are developing a method based on stochastic resonance to enhance information transfer by improving the brain's ability to detect vestibular signals (Vestibular Stochastic Resonance, VSR) especially when combined with balance training exercises such as sensorimotor adaptability (SA) training for rapid improvement in functional skill, for standing and mobility. This countermeasure to improve detection of vestibular signals is a stimulus delivery system that is wearable/portable providing low imperceptible levels of white noise based binaural bipolar electrical stimulation of the vestibular system (stochastic vestibular stimulation). To determine efficacy of vestibular stimulation on physiological and perceptual responses during otolith-canal conflicts and dynamic perturbations we have conducted a series of studies: We have shown that imperceptible binaural bipolar electrical stimulation of the vestibular system across the mastoids enhances balance performance in the mediolateral (ML) plane while standing on an unstable surface. We have followed up on the previous study showing VSR stimulation improved balance performance in both ML and anteroposterior planes while stimulating in the ML axis only. We have shown the efficacy of VSR stimulations on enhancing physiological and perceptual responses of whole-body orientation during low frequency perturbations (0.1 Hz) on the ocular motor system using a variable radius centrifuge on both physiological (using eye movements) and perceptual responses (using a joystick) to track imposed oscillations. The variable radius centrifuge provides a selective tilting sensation that is detectable only by the otolith organs providing conflicting information from the canal organs of the vestibular system (intra-vestibular conflict). These results indicate that VSR can improve performance in sensory conflict scenarios like that experienced during space flight. We have showed the efficacy of VSR stimulation to improve balance and locomotor control on subjects exposed to continuous, sinusoidal lateral motion of the support surface while walking on a treadmill while viewing perceptually matched linear optic flow. We have shown the safety of short term continuous use of up to 4 hours of VSR stimulation and its efficacy in improving balance and locomotor function in Parkinson's Disease patients. This technique for improving vestibular signal detection may thus provide additional information to improve strategic abilities. We hypothesize that VSR stimulation will act synergistically with SA training to improve adaptability by increased utilization of vestibular information and therefore serve to optimize and personalize the SA countermeasure prescription. This forms the basis of its usefulness both as a training modality and further help in significantly reducing the number of days required to recover functional performance to preflight levels after long duration space flight.

Description: This document describes the forward working plan to identify what countermeasure resources are needed for a vehicle with an artificial gravity module (intermittent centrifugation) and what Countermeasure Resources are needed for a rotating transit vehicle (continuous centrifugation) to minimize the effects of microgravity to Mars Exploration crewmembers.

Description: The Visual Impairment/Intracranial Pressure (VIIP) Research and Clinical Advisory Panel convened on December 1, 2014 at the ISS Conference Facility in Houston. The panel members were provided updates to the current clinical cases and treatment plans along with the latest research activities (http://humanresearchroadmap.nasa.gov/Risks/?i=105) and preliminary study results. The following is a summary of this meeting.

Description: Evaluation of the astronaut shoulder injury rates began with an operational concern at the Neutral Buoyancy Laboratory (NBL) during Extravehicular Activity (EVA) training. An astronaut suffered a shoulder injury during an NBL training run and commented that it was possibly due to a hardware issue. During the subsequent investigation, questions arose regarding the rate of shoulder injuries in recent years and over the entire history of the astronaut corps.

Description: Lung cancer induced from exposure to space radiation is believed to be one of the most significant health risks for long-term space travels. In a previous study, normal human bronchial epithelial cells (HBECs), immortalized through the expression of Cdk4 and hTERT, were exposed to gamma rays and high energy Fe ions for the selection of transformed clones induced by low- and high-LET radiation. In this research, we analyzed chromosome aberrations in these selected clones for genomic instability using the multi-color fluorescent in situ hybridization (mFISH), as well as the multi-banding in situ hybridization (mBAND) techniques. In most of the clones, we found chromosomal aberrations involving translocations between different chromosomes, with several of the breaks occurred in the q-arm of chromosome 3. We also identified copy number variations between the transformed clones and the parental HBEC cells regardless of the exposure condition. Our results indicated that the chromosomal aberrations in low- and high radiation-induced transformed clones are inadequately different from spontaneous soft agar growth. Further analysis is underway to reveal the genomic instability in more transformed clones

Description: Understanding the nuances in clinical data is critical in developing a successful data analysis plan. Carbon dioxide (CO2) data are collected on board the International Space Station (ISS) in a continuous stream. Clinical data on ISS are primarily collected via conversations between individual crewmembers and NASA Flight Surgeons during weekly Private Medical Conferences (PMC). Law, et.al, 20141 demonstrated a statistically significant association between weekly average CO2 levels on ISS and self-reported headaches over the reporting period from March 14, 2001 to May 31, 2012. The purpose of this analysis is to describe the evaluation of a possible association between visual changes and CO2 levels on ISS and to discuss challenges in developing an appropriate analysis plan. METHODS & PRELIMINARY RESULTS: A first analysis was conducted following the same study design as the published work on CO2 and self-reported headaches1; substituting self-reported changes in visual acuity in place of self-reported headaches. The analysis demonstrated no statistically significant association between visual impairment characterized by vision symptoms self-reported during PMCs and ISS average CO2 levels over ISS missions. Closer review of the PMC records showed that vision outcomes are not well-documented in terms of clinical severity, timing of onset, or timing of resolution, perhaps due to the incipient nature of vision changes. Vision has been monitored in ISS crewmembers, pre- and post-flight, using standard optometry evaluations. In-flight visual assessments were limited early in the ISS program, primarily consisting of self-perceived changes reported by crewmembers. Recently, on-orbit capabilities have greatly improved. Vision data ranges from self-reported post-flight changes in visual acuity, pre- to postflight changes identified during fundoscopic examination, and in-flight progression measured by advanced on-orbit clinical imaging capabilities at predetermined testing intervals. In contrast, CO2 data are recorded in a continuous stream over time; however, for the initial analysis this data was categorized into weekly averages.

Description: Iron stores are increased secondary to neocytolysis of red blood cells and a high dietary intake of iron during space flight. This raises concerns about the risk of excess iron causing oxidative damage in many tissues, including bone. Biomarkers of iron status, oxidative damage, and bone resorption during space flight were analyzed for 23 (16 M/7 F) International Space Station crewmembers as part of the Nutrition SMO project. Up to 5 in-flight blood samples and 24-h urine pools were collected over the course of the 4-6 month missions. Serum iron increased slightly during space flight and was decreased at landing (P 〈 0.0004). An increase in serum ferritin early in flight (217% in women and 68% in men, P 〈 0.0004), returning to preflight concentrations at landing, and a decrease in transferrin and transferrin receptors during flight indicated that a transient increase in iron stores occurred. No inflammatory response was observed during flight. The oxidative damage markers 8-hydroxy-2'-deoxyguanosine and prostaglandin F(sub 2(alpha)) were positively correlated (both P 〈 0.001) with serum ferritin. A greater area under the curve for ferritin during flight was correlated with greater changes in bone mineral density of several bone regions after flight (1). In a separate study (2), a ground-based investigation was conducted that examined the combined effects of radiation exposure and iron overload on sensitivity to radiation injury in several physiological systems in 12-wk male Sprague-Dawley rats. The rats were acclimated to an adequate iron diet (45 mg iron (ferric citrate)/kg diet) for 3 wk and then assigned to one of four groups: adequate iron (Fe) diet/no radiation, adequate Fe diet/ radiation, moderately high Fe diet (650 mg Fe (ferric citrate)/kg diet)/no radiation, and moderately high Fe diet/radiation. Animals remained on the assigned diet for 4 wk. Starting on day 14 of experimental diet treatment, animals were exposed to a fractionated dose (0.375 Gy) of Cs-137 every other day (3 Gy total dose). On day 29 (24 h after last radiation exposure), animals were euthanized. Oxidative stress markers in the liver, bone, eyes, and serum were assessed. There was evidence that the iron diet contributed to DNA damage as well as radiation exposure in the liver, eyes, and bone. Together, the results suggest that increased iron stores do constitute a risk factor for oxidative damage and bone resorption, during space flight and on Earth. Funded by the Human Health and Countermeasures Element of the NASA Human Research Program.

Description: Currently, NASA does not have sufficient in-flight anthropometric data gathered to assess the impact of physical body shape and size changes on suit sizing. For developing future planetary and reduced gravity suits, NASA needs to quantify the impacts of microgravity on anthropometry, body posture, and neutral body postures (NBP) to ensure optimal crew performance, fit, and comfort. To obtain these impacts, anthropometric data, circumference, length, height, breadth, and depth for body segments (i.e. chest, waist, bicep, thigh, calf) from astronauts for pre, in-, and postflight conditions needs to be collected. Once this data has been collected, a comparison between pre, in-, and postflight anthropometric values will be analyzed, yielding microgravity factors. The NBP will be used to determined body posture (joint angle) changes between subjects throughout the duration of a mission. Data collection, starting with Increments 37/38, is still in progress with the completion of 3 out of 12 subjects. NASA suit engineers and NASA's Extravehicular Activity (EVA) Project Office have identified that suit fit in microgravity could become an issue. It has been noted that crewmembers often need to adjust their suit sizing once they are in orbit. This adjustment could be due to microgravity effects on anthropometry and postural changes, and is necessary to ensure optimal crew performance, fit, and comfort in space. To date, the only data collected to determine the effects of microgravity on physical human changes have been during Skylab, STS-57, and a recent HRP study on seated height changes due to spinal elongation (Spinal Elongation, Master Task List [MTL] #221). The Skylab and the STS-57 studies found that there is a distinct neutral body posture (NBP) based on photographs. The still photographs showed that there is a distinguishable posture with the arms raised and the shoulder abducted; and, in addition, the knees were flexed with noticeable hip flexion and the foot plantar flexed [1,2]. This is the one standard set of body joint angles for a NBP in microgravity. A recent simulated microgravity NBP study [3] has shown an individual variability and inconsistencies in defining NBP. This variation may be influenced by spinal growth, the type of suit fit, and other potential anthropometry factors such as spinal curvature, age, and gender. The variation aspect of this essential data is required for all kinds of space device designs (e.g. suits, habitat, mobility aids, etc.). The method proposed considers the dynamic nature of body movement and will use a measurement technique to continually monitor posture and develop a probability likelihood of the natural posture and how the NBP postures are affected by anthropometry. Additionally, Skylab studies found that crewmembers experienced a stature growth of up to 3%. The data included 3 crewmembers that showed that there is a bi-phasic stature growth once the crew enters into weightlessness. However, the Spinal Elongation study identified that the crewmembers could experience about a 6% growth in seated height and a 3% stature growth, when exposed to microgravity. The results prove that not all anthropometric measurements have the same microgravity percent growth factor. For EVA and suit engineers to properly update the sizing protocol for microgravity, they need additional anthropometric data from space missions. Hence, this study is aimed to gather additional in-flight anthropometric measurements, such as length, depth, breadth, and circumference, to determine the changes to body shape and size due to microgravity effects. It is anticipated that by recording the potential changes to body shape and size, a better suit sizing protocol will be developed for ISS and other space missions. In essence, this study will help NASA quantify the impacts of microgravity on anthropometry to ensure optimal crew performance, fit, and comfort. This study will use simplistic data collection techniques, 3D laser scanning, digital still, and video data, and perform photogrammetric analyses to determine the changes that occur to the body shape, size, and NBP when exposed to a microgravity environment.

Description: No abstract available

Description: Dual-energy x-ray absorptiometry [DXA] is the widely-applied bone densitometry method used to diagnose osteoporosis in a terrestrial population known to be at risk for age-related bone loss. This medical test, which measures areal bone mineral density [aBMD] of clinically-relevant skeletal sites (e.g., hip and spine), helps the clinician to identify which persons, among postmenopausal women and men older than 50 years, are at high risk for low trauma or fragility fractures and might require an intervention. The most recognized osteoporotic fragility fracture is the vertebral compression fracture which can lead to kyphosis or hunched backs typically seen in the elderly. DXA measurement of BMD however is recognized to be insufficient as a sole index for assessing fracture risk. DXA's limitation may be related to its inability to monitor changes in structural parameters, such as trabecular vs. cortical bone volumes, bone geometry or trabecular microarchitecture. Hence, in order to understand risks to human health and performance due to space exposure, NASA needs to expand its measurements of bone to include other contributors to skeletal integrity. To this aim, the Bone and Mineral Lab conducted a pilot study for a novel measurement of bone microarchitecture that can be obtained by retrospective analysis of DXA scans. Trabecular Bone Score (TBS) assesses changes to trabecular microarchitecture by measuring the grey color "texture" information extracted from DXA images of the lumbar spine. An analysis of TBS in 51 ISS astronauts was conducted to assess if TBS could detect 1) an effect of spaceflight and 2) a response to countermeasures independent of DXA BMD. In addition, changes in trunk body lean tissue mass and in trunk body fat tissue mass were also evaluated to explore an association between body composition, as impacted by ARED exercise, and bone microarchitecture. The pilot analysis of 51 astronaut scans of the lumbar spine suggests that, following an ISS mission, DXA BMD and TBS are detecting different effects of ARED exercise and of ARED + Bisphosphonate on the lumbar spine of astronauts. There is emerging evidence associating reduced TBS with terrestrial metabolic bone disorders where a TBS 〈1.200 is associated with "degraded" while 〉 1.350 is associated with "normal." However, it is not possible to conclude how the spaceflight-induced changes in TBS increase risk for vertebral fractures in the astronaut or if changes in body composition of the trunk region could be an indirect method of assessing exercise effect on bone microarchitecture. More importantly, this pilot analysis demonstrates a new, minimal risk approach for monitoring changes to vertebral bone microarchitecture. This method could help assess the combined skeletal effects of spaceflight with the effects of aging in the astronaut after return to Earth.

Description: No abstract available

Description: Spaceflight missions expose astronauts to novel operational and environmental conditions that pose health risks that are currently not well understood, and perhaps unanticipated. Furthermore, given the limited number of humans that have flown in long duration missions and beyond low Earth-orbit, the amount of research and clinical data necessary to predict and mitigate these health and performance risks are limited. Consequently, NASA's Human Research Program (HRP) conducts research and develops advanced methods and tools to predict, assess, and mitigate potential hazards to the health of astronauts. In this light, NASA has explored the possibility of leveraging computational modeling since the 1970s as a means to elucidate the physiologic risks of spaceflight and develop countermeasures. Since that time, substantial progress has been realized in this arena through a number of HRP funded activates such as the Digital Astronaut Project (DAP) and the Integrated Medical Model (IMM). Much of this success can be attributed to HRP's endeavor to establish rigorous verification, validation, and credibility (VV&C) processes that ensure computational models and simulations (M&S) are sufficiently credible to address issues within their intended scope. This presentation summarizes HRP's activities in credibility of modeling and simulation, in particular through its outreach to the community of modeling and simulation practitioners. METHODS: The HRP requires all M&S that can have moderate to high impact on crew health or mission success must be vetted in accordance to NASA Standard for Models and Simulations, NASA-STD-7009 (7009) [5]. As this standard mostly focuses on engineering systems, the IMM and DAP have invested substantial efforts to adapt the processes established in this standard for their application to biological M&S, which is more prevalent in human health and performance (HHP) and space biomedical research and operations [6,7]. These methods have also generated substantial interest by the broader medical community though institutions like the National Institutes of Health (NIH) and the Food and Drug Administration (FDA) to develop similar standards and guidelines applicable to the larger medical operations and research community. DISCUSSION: Similar to NASA, many leading government agencies, health institutions and medical product developers around the world are recognizing the potential of computational M&S to support clinical research and decision making. In this light, substantial investments are being made in computational medicine and notable discoveries are being realized [8]. However, there is a lack of broadly applicable practice guidance for the development and implementation of M&S in clinical care and research in a manner that instills confidence among medical practitioners and biological researchers [9,10]. In this presentation, we will give an overview on how HRP is working with the NIH's Interagency Modeling and Analysis Group (IMAG), the FDA and the American Society of Mechanical Engineers (ASME) to leverage NASA's biomedical VV&C processes to establish a new regulatory standard for Verification and Validation in Computational Modeling of Medical Devices, and Guidelines for Credible Practice of Computational Modeling and Simulation in Healthcare.

Description: One of the greatest challenges surrounding adaptation to the spaceflight environment is the large variability in symptoms, and corresponding functional impairments, from one crewmember to the next. This renders preflight training and countermeasure development difficult, as a "one-size-fits-all" approach is inappropriate. Therefore, it would be highly advantageous to know ahead of time which crewmembers might have more difficulty adjusting to the novel g-levels inherent to spaceflight. Such knowledge could guide individually customized countermeasures, which would enable more efficient use of crew time, both preflight and inflight, and provide better outcomes. The primary goal of this project is to look for a baseline performance metric that can forecast sensorimotor adaptability without exposure to an adaptive stimulus. We propose a novel hypothesis that considers baseline inter-trial correlations, the trial-to-trial fluctuations in motor performance, as a predictor of individual sensorimotor adaptive capabilities. To-date, a strong relationship has been found between baseline inter-trial correlations and adaptability in two oculomotor systems. For this project, we will explore an analogous predictive mechanism in the locomotion system. METHODS: Baseline Inter-trial Correlations: Inter-trial correlations specify the relationships among repeated trials of a given task that transpire as a consequence of correcting for previous performance errors over multiple timescales. We can quantify the strength of inter-trial correlations by measuring the decay of the autocorrelation function (ACF), which describes how rapidly information from past trials is "forgotten." Processes whose ACFs decay more slowly exhibit longer-term inter-trial correlations (longer memory processes), while processes whose ACFs decay more rapidly exhibit shorterterm inter-trial correlations (shorter memory processes). Longer-term correlations reflect low-frequency activity, which is more easily measured in the frequency domain. Therefore, we use the power spectrum (PS), which is the Fourier transform of the ACF, to describe our inter-trial correlations. The decay of the PS yields a straight line on a log-log frequency plot, which we quantify by Beta = - (slope of PS on log-log axes). Hence, Beta is a measure of the strength of inter- trial correlations in the baseline data. Larger Beta values are indicative of longer inter-trial correlations. Experimental Approach: We will begin by performing a retrospective analysis of treadmill-gait adaptation data previously collected by Dr. Bloomberg and colleagues. Specifically, we will quantify the strength of inter-trial correlations in the baseline step cadence and heart rate data and compare it to the locomotor adaptability performance results already described by these investigators. Incorporating these datasets will also allow us to explore the applicability of (and potential limitations surrounding) the use of Beta in forecasting physiological performance. We will also perform a new experiment, in which Beta will be derived from baseline data collected during over-ground (non-treadmill) walking, which will enable us to consider locomotor performance, through the parameter Beta, under the most functionallyrelevant, natural gait condition. This experiment will incorporate two baseline and five post-training over-ground locomotion tests to explore the consistency and potential adaptability of the Beta values themselves. HYPOTHESES: We hypothesize that the strength of baseline inter-trial correlations of step cadence and heart rate will relate to locomotor adaptability. Specifically, we anticipate that individuals who show weaker longer-term inter-trial correlations in baseline step cadence data will be the better adaptors, as step cadence can be modified in real-time (i.e., online corrections are an inherent property of the locomotor system; analogous to results observed in the VOR). Conversely, because heart rate is not altered mid-beat, we expect that individuals who demonstrate stronger longer-term correlations in heart rate will be the better adaptors (analogous to results observed in the saccadic system). CONCLUSIONS: At the conclusion of this project we hope to uncover a baseline predictor of locomotor adaptability. If our hypotheses hold true, our results will demonstrate that the temporal structure of baseline behavioral data contains important information that may aid in forecasting adaptive capacities. The ability to predict such adaptability in the sensorimotor system has significant implications for spaceflight, where astronauts must adjust their motor programs following a change in g-level to retain movement accuracy.

Description: Despite significant progress understanding biological radiation effects via terrestrial studies, no terrestrial source duplicates spaces unique radiation environment. Furthermore, no biological experiments have been conducted beyond low Earth orbit since Apollo. Understanding spaces fundamental biological effects requires overcoming these limitations. The BioSentinel 4U payload, under development for flight aboard Exploration Mission-1, measures biological responses to deep space radiation. Traveling to more than 1AU from Earth, BioSentinel/EM-1 will record DNA double-strand breaks (DSBs) repaired using a pathway common to humans and BioSentinels bioengineered yeast model organism, responding to as few as one biologically repaired DSB. The BioSentinel/Mars 4U instrument (6-8kg; 5-8W; 0.2-1MB/week) would include eighteen 16-well biosensor fluidic cards, activated biweekly during Mars 2020s cruise phase, to provide a dose-dependent rate of DSB/repair. The instrument, which includes solid-state sensors for total ionizing dose and linear-energy-transfer spectra, addresses MEPAG SKG-B3 by simultaneously measuring both spectra and biological effects of space radiation. Biological measurements are rendered reliable by independent replicate experiments. The spatio-temporal uniformity of interplanetary galactic cosmic radiation makes BioSentinel/EM1 and BioSentinel/Mars approximate replicates, except for any major differences in solar particle events. Results will be compared to Earth and ISS controls to characterize the radiation/reduced-gravity parameter space by its biological impact.

Description: Research by NASA has established that significant risks for visual impairment in association with increased intracranial pressure (VIIP) are incurred by microgravity spaceflight, especially long-duration missions. Impairments include decreased near visual acuity, posterior globe flattening, choroidal folds, optic disc edema, and cotton wool spots. Much remains to be learned about the etiology of VIIP before effective countermeasures can be developed. Contributions of retinal vascular remodeling to the etiology of VIIP have not yet been investigated, primarily due to the current lack of ophthalmic tools for precisely measuring progressive pathophysiological remodeling of the retinal microvasculature. Although ophthalmic science and clinical practice are now highly sophisticated at detecting indirect, secondary signs of vascular remodeling such as cotton wool spots that arise during the progression of retinal vascular diseases, methods for quantifying direct, primary vascular changes are not yet established. To help develop insightful analysis of retinal vascular remodeling for aerospace medicine, we will map and quantify by our innovative VESsel GENeration Analysis (VESGEN) software the remodeling status of retinal blood vessels in crew members before and after ISS missions, and in healthy human subjects before and after head-down tilt bed rest. For this proof-of-concept study, we hypothesize that pathophysiological remodeling of retinal blood vessels occurs in coordination with microgravity-induced fluid shifts prior to development of visual impairments. VESGEN analysis in previous research supported by the US National Institutes of Health identified surprising new opportunities to regenerate retinal vessels during early-stage progression of the visually impairing, potentially blinding disease, diabetic retinopathy.

Description: Numerous published studies have reported the RBE values for chromosome chromosomes induced by charged particles of different LET. The RBE for chromosome aberrations in human lymphocytes exposed ex vivo showed a similar relationship as the quality factor for cancer induction. Consequently, increased chromosome aberrations in the astronauts' white blood cells post long-duration missions are used to determine the biological doses from exposures to space radiation. The RBE value is known to be very different for different types of cancer. Previously, we reported that the RBE for initial chromosome damages was high in human lymphocytes exposed to Fe ions. After multiple cell divisions post irradiation, the RBE was significantly smaller. To test the hypothesis that the RBE values for chromosome aberrations are different between early and late damages and also different between different cell types, we exposed human lymphocytes ex vivo, and human fibroblast cells and human mammary epithelial cells in vitro to 600 MeV/u Fe ions. Post irradiation, the cells were collected at first mitosis, or cultured for multiple generations for collections of remaining or late arising chromosome aberrations. The chromosome aberrations were quantified using fluorescent in situ hybridization (FISH) with whole chromosome specific probes. This study attempts to offer an explanation for the varying RBE values for different cancer types.

Description: BACKGROUND: A previous study [1] reported that the instantaneous risk of developing a Herniated Nucleus Pulposus (HNP) was higher in astronauts who had flown at least one mission, as compared with those in the corps who had not yet flown. However, the study only analyzed time to HNP after the first mission (if any) and did not account for the possible effects of multiple missions. While many HNP's occurred well into astronauts' careers or in some cases years after retirement, the higher incidence of HNPs relatively soon after completion of space missions appears to indicate that spaceflight may lead to an increased risk of HNP. The purpose of this study was to support the Human System Risk Board assessment of back pain, evaluate the risk of injury due to dynamic loads, and update the previous dataset which contained events up to December 31, 2006. METHODS: Data was queried from the electronic medical record and provided by the Lifetime Surveillance of Astronaut Health. The data included all 330 United States astronauts from 1959 through February 2014. Cases were confirmed by Magnetic Resonance Imaging, Computerized Tomography, Myelography, operative findings, or through clinical confirmation with a neurologist or neurosurgeon. In this analysis, astronauts who had an HNP at selection into the corps or had an HNP diagnosis prior to their first flight were excluded. The statistical challenges in using the available data to separate effects of spaceflight from those associated with general astronaut training and lifestyle on propensity to develop HNPs are many. The primary outcome is reported date of first HNP (if any), which at best is only an approximation to the actual time of occurrence. To properly analyze this data with a survival analysis model, one must also know the "exposure" time - i.e. how long each astronaut has been at risk for developing an HNP. If an HNP is reported soon after a mission, is it mission caused or general? If the former, exposure time should be counted from the time of landing (assuming the risk of HNP occurring during a mission is zero). If the latter, exposure time should be counted from the time of selection; however we can't directly know which one to use. In our analysis we take both of these possibilities into account with a competing risks model, wherein two distinct stochastic processes are going on: TG = time to HNP (general) and TS = time to HNP (spaceflight). Under this type of model, whichever of these occurs first is what we observe; in other words we don't observe TG or TS, only min(TG, TS). Here, we parameterized the model in terms of separate Weibull hazard functions for each process and estimated all parameters using maximum likelihood. In addition, we allowed for a "cured fraction" - i.e. the possibility that some astronauts may never develop an HNP. RESULTS: Results will include a depiction of the competing hazard functions as well as a probability curve for the relative likelihood that an HNP reported at a given time after a mission is actually mission caused. Other factors, such as dwell time in microgravity and vehicle landing environment will be explored. An overall assessment as to whether spaceflight truly exacerbates HNP risk will be made.

Description: Astronauts experience sensorimotor disturbances during the initial exposure to microgravity and during the readapation phase following a return to a gravitational environment. These alterations may lead to disruption in the ability to perform mission critical functions during and after these gravitational transitions. Astronauts show significant inter-subject variation in adaptive capability following gravitational transitions. The way each individual's brain synthesizes the available visual, vestibular and somatosensory information is likely the basis for much of the variation. Identifying the presence of biases in each person's use of information available from these sensorimotor subsystems and relating it to their ability to adapt to a novel locomotor task will allow us to customize a training program designed to enhance sensorimotor adaptability. Eight tests are being used to measure sensorimotor subsystem performance. Three of these use measures of body sway to characterize balance during varying sensorimotor challenges. The effect of vision is assessed by repeating conditions with eyes open and eyes closed. Standing on foam, or on a support surface that pitches to maintain a constant ankle angle provide somatosensory challenges. Information from the vestibular system is isolated when vision is removed and the support surface is compromised, and it is challenged when the tasks are done while the head is in motion. The integration and dominance of visual information is assessed in three additional tests. The Rod & Frame Test measures the degree to which a subject's perception of the visual vertical is affected by the orientation of a tilted frame in the periphery. Locomotor visual dependence is determined by assessing how much an oscillating virtual visual world affects a treadmill-walking subject. In the third of the visual manipulation tests, subjects walk an obstacle course while wearing up-down reversing prisms. The two remaining tests include direct measures of knee and ankle proprioception and a functional movement assessment that screens for movement restrictions and asymmetries. To assess each subject's locomotor adaptability subjects walk for twenty minutes on a treadmill that oscillates laterally at 0.3 Hz. Throughout the test metabolic cost provides a measure of exertion and step frequency provides a measure of stability. Additionally, at four points during the perturbation period, reaction time tests are used to probe changes in the amount of mental effort being used to perform the task. As with the adaptive capability observed in astronauts during gravitational transitions, our data shows significant variability between subjects. To aid in the analysis of the results, custom software tools have been developed to enhance in the visualization of the large number of output variables. Preliminary analyses of the data collected to date do not show a strong relationship between adaptability and any single predictor variable. Analysis continues to identify a multifactorial predictor outcome "signature" that do inform us of locomotor adaptability.

Description: This work was accomplished in support of the Finite Element [FE] Strength Task Group, NASA Johnson Space Center [JSC], Houston, TX. This group was charged with the task of developing rules for using finite-element [FE] bone-strength measures to construct operating bands for bone health that are relevant to astronauts following exposure to spaceflight. FE modeling is a computational tool used by engineers to estimate the failure loads of complex structures. Recently, some engineers have used this tool to characterize the failure loads of the hip in population studies that also monitored fracture outcomes. A Directed Research Task was authorized in July, 2012 to investigate FE data from these population studies to derive these proposed standards of bone health as a function of age and gender. The proposed standards make use of an FE-based index that integrates multiple contributors to bone strength, an expanded evaluation that is critical after an astronaut is exposed to spaceflight. The current index of bone health used by NASA is the measurement of areal BMD. There was a concern voiced by a research and clinical advisory panel that the sole use of areal BMD would be insufficient to fully evaluate the effects of spaceflight on the hip. Hence, NASA may not have a full understanding of fracture risk, both during and after a mission, and may be poorly estimating in-flight countermeasure efficacy. The FE Strength Task Group - composed of principal investigators of the aforementioned population studies and of FE modelers -donated some of its population QCT data to estimate of hip bone strength by FE modeling for this specific purpose. Consequently, Human Health Countermeasures [HHC] has compiled a dataset of FE hip strengths, generated by a single FE modeling approach, from human subjects (approx.1060) with ages covering the age range of the astronauts. The dataset has been analyzed to generate a set of FE strength cutoffs for the following scenarios: a) Qualify an applicant for astronaut candidacy, b) Qualify an astronaut for a long-duration (LD) mission, c) Qualify a veteran LD astronaut for a second LD mission, and d) Establish a non-permissible, minimum hip strength following a given mission architecture. This abstract will present the FE-based standards accepted by the FE Strength Task Group for its recommendation to HHC in January 2015.

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

Description: The primary goal of this research is to determine functional abilities associated with long-duration space flight crews beginning as soon after landing as possible (〈 2 hours) with an additional two follow-up measurements sessions on the day of landing. This goal has both sensorimotor and cardiovascular elements, including evaluations of NASA's new anti-orthostatic compression garment and the Russian Kentavr garment. Functional sensorimotor measurements will include, but are not limited to, assessing hand/eye coordination, standing from a seated position (sit-to-stand), walking normally without falling, measurement of dynamic visual acuity, discriminating different forces generated with both the hands and legs, recovering from a fall (standing from a prone position), coordinated walking involving tandem heel-to-toe placement, and determining postural ataxia while standing. The cardiovascular portion of the investigation includes measuring blood pressure and heart rate during a timed stand test in conjunction with postural ataxia testing (quiet stance sway) as well as cardiovascular responses during the other functional tasks. In addition to the immediate post-landing collection of data for the full FT, postflight data is being acquired twice more within the 24 hours after landing and will continue over the subsequent weeks until functional sensorimotor and cardiovascular responses have returned to preflight normative values. The PFT represents a initial evaluation of the feasibility of testing in the field, and is comprised of a jointly agreed upon subset of tests from the full FT and relies heavily on Russia's Institute of Biomedical Problems Sensory-Motor and Countermeasures Laboratories for content and implementation. The PFT has been collected on several ISS missions. Testing on the U.S. side has included: (1) a sit-to-stand test, (2) recovery from a fall where the crewmember began in the prone position on the ground and then stood for 3 minutes while cardiovascular stability was determined and postural ataxia data were acquired, and (3) a tandem heel-to-toe walk test to determine changes in the central locomotor program. Video, cardiovascular parameters (heart rate and blood pressure), data from bodyworn inertial sensors, and severity of postflight motion sickness were collected during each test session. Our Russian investigators have added measurements associated with: (a) obstacle avoidance, (b) muscle compliance and (c) postural adjustments to perturbations (push) applied to the subject's chest area. The level of functional deficit observed in the crew tested to date is typically beyond what was expected and is clearly triggered by the acquisition of gravity loads immediately after landing when the demands for crew intervention in response to emergency operations will be greatest. Clearly measureable performance parameters such as ability to perform a seat egress, recover from a fall or the ability to see clearly when walking, and related physiologic data (orthostatic responses) are required to provide an evidence base for characterizing programmatic risks and the degree of variability among crewmembers for exploration missions where the crew will be unassisted after landing. Overall, these early functional and related physiologic measurements will allow the estimation of nonlinear sensorimotor and cardiovascular recovery trends that have not been previously captured

Description: Musculoskeletal activity has the potential to both improve and compromise decompression safety. Exercise enhances inert gas elimination during oxygen breathing prior to decompression (prebreathe), but it may also promote bubble nuclei formation (nucleation), which can lead to gas phase separation and bubble growth and increase the risk of decompression sickness (DCS). The timing, pattern and intensity of musculoskeletal activity and the level of tissue supersaturation may be critical to the net effect. There are limited data available to evaluate cost-benefit relationships. Understanding the relationship is important to improve our understanding of the underlying mechanisms of nucleation in exercise prebreathe protocols and to quantify risk in gravity and microgravity environments. Data gathered during NASA's Prebreathe Reduction Program (PRP) studies combined oxygen prebreathe and exercise followed by low pressure (4.3 psi; altitude equivalent of 30,300 ft [9,235 m]) microgravity simulation to produce two protocols used by astronauts preparing for extravehicular activity. Both the Phase II/CEVIS (cycle ergometer vibration isolation system) and ISLE (in-suit light exercise) trials eliminated ambulation to more closely simulate the microgravity environment. The CEVIS results (35 male, 10 female) serve as control data for this NASA/Duke study to investigate the influence of ambulation exercise on bubble formation and the subsequent risk of DCS.

Description: A process for purifying laccase from an ectomycorrhizal fruiting body is disclosed. The process includes steps of homogenization, sonication, centrifugation, filtration, affinity chromatography, ion exchange chromatography, and gel filtration. Purified laccase can also be separated into isomers.

Description: Insertion of astronauts into microgravity induces a cascade of physiological adaptations, notably including a cephalad fluid shift. Longer-duration flights carry an increased risk of developing Visual Impairment and Intracranial Pressure (VIIP) syndrome, a spectrum of ophthalmic changes including posterior globe flattening, choroidal folds, distension of the optic nerve sheath, kinking of the optic nerve and potentially permanent degradation of visual function. The slow onset of changes in VIIP, their chronic nature, and the similarity of certain clinical features of VIIP to ophthalmic findings in patients with raised intracranial pressure strongly suggest that: (i) biomechanical factors play a role in VIIP, and (ii) connective tissue remodeling must be accounted for if we wish to understand the pathology of VIIP. Our goal is to elucidate the pathophysiology of VIIP and suggest countermeasures based on biomechanical modeling of ocular tissues, suitably informed by experimental data, and followed by validation and verification. We specifically seek to understand the quasi-homeostatic state that evolves over weeks to months in space, during which ocular tissue remodeling occurs. This effort is informed by three bodies of work: (i) modeling of cephalad fluid shifts; (ii) modeling of ophthalmic tissue biomechanics in glaucoma; and (iii) modeling of connective tissue changes in response to biomechanical loading.

Description: No abstract available

Description: Astronauts perform exercise throughout their missions to counter the health declines that occur as a result of long-term exposure to weightlessness. Although all astronauts perform exercise during their missions, the specific prescriptions, and thus the mechanical loading, differs among individuals. For example, inflight ground reaction force data indicate that subject-specific differences exist in foot forces created when exercising on the second-generation treadmill (T2) [1]. The current exercise devices allow astronauts to complete prescriptions at higher intensities, resulting in greater benefits with increased efficiency. Although physiological outcomes have improved, the specific factors related to the increased benefits are unknown. In-flight exercise hardware collect data that allows for exploratory analyses to determine if specific performance factors relate to physiological outcomes. These analyses are vital for understanding which components of exercise are most critical for optimal human health and performance. The relationship between exercise performance variables and physiological changes during flight has yet to be fully investigated. Identifying the critical performance variables that relate to improved physiological outcomes is vital for creating current and future exercise prescriptions to optimize astronaut health. The specific aims of this project are: 1) To quantify the exercise-related mechanical loading experienced by crewmembers on T2 and ARED during their mission on ISS; 2) To explore relationships between exercise loading variables, bone, and muscle health changes during the mission; 3) To determine if specific mechanical loading variables are more critical than others in protecting physiology; 4) To develop methodology for operational use in monitoring accumulated training loads during crew exercise programs. This retrospective analysis, which is currently in progress, is being conducted using data from astronauts that have flown long-duration missions onboard the ISS and have had access to exercise on the T2 and the Advanced Resistive Exercise Device (ARED). The specific exercise prescriptions vary for each astronaut. General exercise summary metrics will be developed to quantify exercise intensities, volumes, and durations for each subject. Where available, ground reaction force data will be used to quantify mechanical loading experienced by each astronaut. These inflight exercise metrics will be investigated relative to changes in pre- to post-flight bone and muscle health to identify which specific variables are related with improved or degraded physiological outcomes. The information generated from this analysis will fill gaps related to typical bone loading characterization, exercise performance capability, exercise volume and efficiency, and importance of exercise hardware. In addition, methods for quantification of exercise loading for use in monitoring the exercise programs during future space missions will be explored with the intent to inform exercise scientists and trainers as to the critical aspects of inflight exercise prescriptions.

Description: The 2014 Bone and Muscle Risks Standing Review Panel (from here on referred to as the SRP) met for a site visit in Houston, TX on December 17 - 18, 2014. The SRP reviewed the updated research plans for the Risk of Impaired Performance Due to Reduced Muscle Mass, Strength and Endurance (Muscle Risk) and the Risk of Reduced Physical Performance Capabilities Due to Reduced Aerobic Capacity (Aerobic Risk). The SRP also received a status update on the Risk of Bone Fracture (Bone Risk), the Risk of Early Onset Osteoporosis Due To Spaceflight (Osteo Risk), the Risk of Intervertebral Disc Damage (IVD Risk), and the Risk of Renal Stone Formation (Renal Risk).

Description: Life has had a profound impact on the geological history of our planet, which in turn has had a profound impact back on the evolution of life. Life has been able to adapt and spread into every planetary nook and cranny. At this point in history, life is becoming able to engineer itself, with extreme consequences we are only dimly able to foresee. One probable outcome will be the facilitation of the expansion of the range of life to beyond our planetary cradle, an evolutionary step as profound as the ancient transition from sea to land. Current efforts at NASA and aboard the International Space Station will be discussed in this context.

Description: No abstract available

Description: The invention provides systems and methods for manipulating biological systems, for example to elicit a more desired biological response from a biological sample, such as a tissue, organ, and/or a cell. In one aspect, the invention operates by efficiently searching through a large parametric space of stimuli and system parameters to manipulate, control, and optimize the response of biological samples sustained in the system. In one aspect, the systems and methods of the invention use at least one optimization algorithm to modify the actuator's control inputs for stimulation, responsive to the sensor's output of response signals. The invention can be used, e.g., to optimize any biological system, e.g., bioreactors for proteins, and the like, small molecules, polysaccharides, lipids, and the like. Another use of the apparatus and methods includes is for the discovery of key parameters in complex biological systems.

Description: No abstract available

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Description: Spontaneous venous pulsations seen on the optic nerve head (optic disc) are presumed to be caused by fluctuations in the pressure gradient between the intraocular and retrolaminar venous systems. The disappearance of previously documented spontaneous venous pulsations is a wellrecognized clinical sign usually associated with a rise in intracranial pressure and a concomitant bilateral elevation of pressure in the subarachnoid space surrounding the optic nerves. In this correspondence we report the unilateral loss of spontaneous venous pulsations in an astronaut 5 months into a long duration space flight. We documented a normal lumbar puncture opening pressure 8 days post mission. The spontaneous venous pulsations were also documented to be absent 21 months following return to Earth.. We hypothesize that these changes may have resulted from a chronic unilateral rise in optic nerve sheath pressure caused by a microgravityinduced optic nerve sheath compartment syndrome.

Description: No abstract available

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Description: The 2014 Decompression Sickness (DCS)/Extravehicular Activity (EVA) Risks Standing Review Panel (from here on referred to as the SRP) met for a site visit in Houston, TX on November 4 - 5, 2014. The SRP reviewed the Research Plans for The Risk of Decompression Sickness and the Risk of Injury and Compromised Performance due to EVA Operations, as well as the Evidence Reports for both of these Risks. The SRP found that the NASA DCS/EVA team did an excellent job of presenting their research plans. The SRP considers it critical that NASA proceeds with the high priority tasks identified in this report (DCS1, DCS3, DCS5). The highest priority is to determine the acceptable DCS and hypoxia risk associated with the planned human exploration beyond low Earth orbit. The risk of DCS is highly dependent upon the pressure within the exploration vehicle. If slightly more hypoxia is permitted then (even with the same percentage of oxygen) the pressure within the exploration vehicle can be lowered thus further mitigating the risk of DCS. The second highest priority is to test and validate the recommended 8.2psi/34% O2 atmosphere. Development of procedures and equipment for human exploration missions are very limited until the results of this testing are completed. The SRP also suggests that DCS7 be separated into two Gaps. Gap DCS7 should deal with DCS treatment while a new Gap should be created to deal with the long-term effects of DCS. The SRP also encourages NASA to increase collaboration with other organizations and pool resources where possible. The current NASA DCS/EVA team has the extensive expertise and a wealth of knowledge in this area. The SRP suggests that increased manpower for this team would be highly productive.

Description: HRP's mission is to reduce the risks to human health and performance during long-duration spaceflight. The HRP Integrated Research Plan (IRP) contains the research plans for the 32 risks that require research to characterize and mitigate. From its inception the "integrate" aspect of the IRP has denoted the integrated nature of risks to human health and performance. Even though each risk in the IRP has its own research plan and is tracked separately, the interrelated nature of health and performance requires that they be addressed in an integrative or holistic fashion so that the connectedness of physiological systems within the human body and the integrated response to spaceflight can be addressed. Common characteristics of the spaceflight environment include altered gravity, atmospheres, and light/dark cycles; space radiation; isolation; noise; and periods of high or low workload. Long-term exposure to this unique environment produces a suite of physiological effects such as stress; vision, neurocognitive, and anthropometric changes; circadian misalignment; fluid shifts; cardiovascular deconditioning; immune dysregulation; and altered nutritional requirements. Expanding cross-disciplinary integrative approaches that synthesize concepts or data from two or more disciplines would improve the identification and characterization risk factors, and enable the development of countermeasures relevant to multiple risks. Cross-disciplinary approaches might also help to illuminate problem areas that may arise when a countermeasure adversely impacts risks other than those which it was developed to mitigate, or to identify groupings of physiological changes that are likely to occur that may impact the overall risk posture. In 2014 HRP embarked on a pilot study that combined four SRPs (and 12 HRP risks) - Behavioral Health, Sensorimotor, Cardiovascular, and Bone/Muscle - specifically to discuss cross-disciplinary integration. The points outlined below were suggested to seed the discussion, within the bounding constraint that research plans must be feasible and relevant to the HRP mission. While these were suggested starting points, the overall guiding principle was to allow free discussion from panel members on any aspect of integrated research that they felt was important, Existing cross-disciplinary integration as documented in the IRP (HRR), Existing or needed integration already identified by HRP, but not yet well defined within the IRP, Areas of integration that are missing.

Description: No abstract available

Description: No abstract available