ALBERT

Description: Studie zu einer prognostizierten Anzahl von Tagen mit Wärme- und mit Kältestress, basierend auf Klimaszenarien für den Zeitraum 2071 bis 2100 KATASTER-BESCHREIBUNG: Prognose: größere Zahl an Todesfällen durch Hitze im Süden gegenüber dem Norden Deutschlands und zugleich größerer Rückgang der Todesfälle durch Kälte im Norden, Anstieg der Todesopferzahl durch zunehmende Hitze insgesamt größer als Rückgang der Opferzahl durch weniger Kälte KATASTER-DETAIL:

Description: Numerous studies have indicated that dysregulation of the immune system occurs during or after spaceflight. Using 21 day -6 degrees head-down tilt bed rest as a spaceflight analog, this study describes the effects of artificial gravity (AG) as a daily countermeasure on immunity, stress and reactivation of clinically important latent herpes viruses. The specific aims were to evaluate psychological and physiological stress, to determine the status of the immune system, and to quantify reactivation of latent herpes viruses. Blood, saliva, and urine samples were collected from each participating subject at different times throughout the study. An immune assessment was performed on all treatment and control subjects that consisted of a comprehensive peripheral immunophenotype analysis, intracellular cytokine profiles and a measurement of T cell function. The treatment group displayed no differences throughout the course of the study with regards to peripheral leukocyte distribution, cytokine production or T cell function. Shedding of Epstein barr virus (EBV), Cytomegalovirus (CMV), and Varicella zoster virus (VZV) was quantified by real time PCR in saliva and urine samples, respectively. There was no significant difference in CMV DNA in the treatment group as compared to the control group. EBV and VZV on the other hand showed a mild reactivation during the study. There were no significant differences in cortisol between the control and treatment groups. In addition, no significant differences between antiviral antibody titers (EBV-VCA, -EA, -EBNA, CMV) or tetramer-positive (EBV, CMV) were found between the two groups. EBV DNA copies in blood were typically undetectable but never exceeded 1,500 copies per 106 PBMCs. Overall, these data indicate that the artificial gravity countermeasure and the 21 day head-down tilt bed rest regimen had no observable adverse effect on immune function.

Description: A growing number of studies show strong associations between stress and altered immune function. In vivo studies of chronic and acute stress have demonstrated that cognitive stressors are strongly correlated with high levels of catecholamines (CT) and corticosteroids (CS). Although both CS and CT individually can inhibit the production of T-helper 1 (TH1, type-1 like) cytokines and simultaneously promote the production of T-helper 2 (TH2, type-2 like) cytokines in antigen-specific and mitogen stimulated human leukocyte cultures in vitro, little attention has been focused on the effects of combination CT and CS in immune responses that may be more physiologically relevant. We therefore investigated the combined effects of in vitro CT and CS upon the type-1/type-2 cytokine balance of human peripheral blood mononuclear cells (PBMC) as a model to study the immunomodulatory effects of superimposed acute and chronic stress. Results demonstrated a significant decrease in type-1 cytokine production (IFN-gamma) and a significant increase in type-2 cytokine production (IL-4, IL-10) in our CS+CT incubated cultures when compared to either CT or CS agents alone. Furthermore, variable enhancement of type-1/type-2 immune deviation occurred depending upon when the CT was added. The data suggest that CS can increase the sensitivity of PBMC to the immunomodulatory effects of CT and establishes an in vitro model to study the combined effects of in vivo type-1/type-2 cytokine alterations observed in acute and chronic stress.

Description: A viewgraph presentation on the Decompression Sickness (DCS) Contingency Plan for manned spaceflight is shown. The topics include: 1) Approach; 2) DCS Contingency Plan Overview; 3) Extravehicular Activity (EVA) Cuff Classifications; 4) On-orbit Treatment Philosophy; 5) Long Form Malfunction Procedure (MAL); 6) Medical Checklist; 7) Flight Rules; 8) Crew Training; 9) Flight Surgeon / Biomedical Engineer (BME) Training; and 10) DCS Emergency Landing Site.

Description: Sonography is the only medical imaging modality aboard the ISS, and is likely to remain the leading imaging modality in future human space flight programs. While trauma sonography (TS) has been well recognized for terrestrial trauma settings, the technique had to be evaluated for suitability in space flight prior to adopting it as an operational capability. The authors found the following four-phased evaluative approach applicable to this task: 1) identifying standard or novel terrestrial techniques for potential use in space medicine; 2) developing and testing these techniques with suggested modifications on the ground (1g) either in clinical settings or in animal models, as appropriate; 3) evaluating and refining the techniques in parabolic flight (0g); and 4) validating and implementing for clinical use in space. In Phase I of the TS project, expert opinion and literature review suggested TS to be a potential screening tool for trauma in space. In Phase II, animal models were developed and tested in ground studies, and clinical studies were carried out in collaborating trauma centers. In Phase III, animal models were flight-tested in the NASA KC-135 Reduced Gravity Laboratory. Preliminary results of the first three phases demonstrated potential clinical utility of TS in microgravity. Phase IV studies have begun to address crew training issues, on-board imaging protocols, and data transfer procedures necessary to offer the modified TS technique for space use.

Description: A review of currently available data on in vivo induced chromosome damage in the blood lymphocytes of astronauts proves that, after protracted exposure of a few months or more to space radiation, cytogenetic biodosimetry analyses of blood collected within a week or two of return from space provides a reliable estimate of equivalent radiation dose and risk. Recent studies indicate that biodosimetry estimates from single spaceflights lie within the range expected from physical dosimetry and biophysical models, but very large uncertainties are associated with single individual measurements and the total sample population remains low. Retrospective doses may be more difficult to estimate because of the fairly rapid time-dependent loss of "stable" aberrations in blood lymphocytes. Also, biodosimetry estimates from individuals who participate in multiple missions, or very long (interplanetary) missions, may be complicated by an adaptive response to space radiation and/or changes in lymphocyte survival and repopulation. A discussion of published data is presented and specific issues related to space radiation biodosimetry protocols are discussed.

Description: The NASA Study of Cataract in Astronauts (NASCA) is a five-year, multi-centered, investigation of lens opacification in populations of U.S. astronauts, military pilots, and ground-based (nonaviator) comparison participants. For astronauts, the explanatory variable of most interest is radiation exposure during space flight, however to properly evaluate its effect, the secondary effects of age, nutrition, general health, solar ocular exposure, and other confounding variables encountered in non-space flight must also be considered. NASCA contains an initial baseline, cross-sectional objective assessment of the severity of cortical (C), nuclear (N), and posterior subcapsular (PSC) lens opacification, and annual follow-on assessments of severity and progression of these opacities in the population of astronauts and in participants sampled from populations of military pilots and ground-based exposure controls. From these data, NASCA will estimate the degree to which space radiation affects lens opacification for astronauts and how the overall risks of each cataract type for astronauts compared with those of the other exposure control groups after adjusting for differences in age and other explanatory variables.

Description: Immune system dysregulation has been demonstrated to occur during spaceflight and has the potential to cause serious health risks to crewmembers participating in exploration-class missions. A comprehensive immune assessment was recently performed on 13 short duration Space Shuttle crewmembers and 8 long duration International Space Station (ISS) crewmembers. Statistically significant post-flight phenotype alterations (as compared to pre-flight baseline) for the Shuttle crewmembers included: granulocytosis, increased percentage of B cells, reduced percentage of NK cells, elevated CD4/CD8 ratio, elevated levels of memory CD4+ T cells, and a CD8+ T cell shift to a less differentiated state. For the Shuttle crewmembers, T cell function was surprisingly elevated post-flight, among both the CD4+ and CD8+ subsets. This is likely an acute stress response in less-deconditioned crewmembers. The percentage of CD4+/IL-2+, CD4+/IFNg+ and CD8+/IFNg+ T cells were all decreased at landing. Culture secreted IFNg production was significantly decreased at landing, whereas production of Th2 cytokines was largely unchanged. It was found that the IFNg:IL-10 ratio was obviously declined in the Shuttle crewmembers immediately post-flight. A similar pattern of alterations were observed for the long duration ISS crewmembers. In contrast to Shuttle crewmembers, the ISS crewmembers demonstrated a dramatic reduction in T cell function immediately post-flight. This may be related to the effect of acute landing stress in conjunction with prolonged deconditioning associated with extended flight. The reduction in IFNg:IL-10 ratio (Th2 shift) was also observed post-flight in the ISS crewmembers to a much higher degree. These data indicate consistent peripheral phenotype changes and altered cytokine production profiles occur following space travel of both short and long duration.

Description: Biologists typically define living organisms as carbon and water-based cellular forms with :self-replication" as the fundamental trait of the life process. However, this standard dictionary definition of life does not help scientists to categorize self-replicators like viruses, prions, proteons and artificial life. CNP also named nanobacteria were discovered in early 1990s as about 100 nanometer-sized bacteria-like particles with unique apatite mineral-shells around them, and found to be associated with pathological-calcification related diseases. Although CNP have been isolated and cultured from mammalian blood and diseased calcified tissues, and their biomineralizing properties well established, their biological nature and self-replicating capability have always been severely challenged. The terms "self-replication", "self-assembly" or "self-propagation" have been widely used for all systems including nanomachines, crystals, computer viruses and memes. In a simple taxonomy, all biological and non-biological "self replicators", have been classified into "living" or "nonliving" based on the properties of the systems and the amount of support they require to self-replicate. To enhance our understanding about self-replicating nature of CNP, we have investigated their growth in specific culture conditions using conventional inverted light microscope and BioStation IM, Nikon s latest time-lapse imaging system. Their morphological structure was examined using scanning (SEM) and transmission (TEM) electron microscopy. This present study, in conjunction with previous findings of metabolic activity, antibiotic sensitivity, antibody specificity, morphological aspects and infectivity, all concomitantly validate CNP as living self-replicators.

Description: Microgravity of spaceflight induces bone loss due in part to decreased bone formation by osteoblasts. We have previously examined the microgravity-induced changes in gene expression profiles in 2T3 preosteoblasts using the Random Positioning Machine (RPM) to simulate microgravity conditions. Here, we hypothesized that exposure of preosteoblasts to an independent microgravity simulator, the Rotating Wall Vessel (RWV), induces similar changes in differentiation and gene transcript profiles, resulting in a more confined list of gravi-sensitive genes that may play a role in bone formation. In comparison to static 1g controls, exposure of 2T3 cells to RWV for 3 days inhibited alkaline phosphatase activity, a marker of differentiation, and downregulated 61 genes and upregulated 45 genes by more than two-fold as shown by microarray analysis. The microarray results were confirmed with real time PCR for downregulated genes osteomodulin, bone morphogenic protein 4 (BMP4), runx2, and parathyroid hormone receptor 1. Western blot analysis validated the expression of three downregulated genes, BMP4, peroxiredoxin IV, and osteoglycin, and one upregulated gene peroxiredoxin I. Comparison of the microarrays from the RPM and the RWV studies identified 14 gravi-sensitive genes that changed in the same direction in both systems. Further comparison of our results to a published database showing gene transcript profiles of mechanically loaded mouse tibiae revealed 16 genes upregulated by the loading that were shown to be downregulated by RWV and RPM. These mechanosensitive genes identified by the comparative studies may provide novel insights into understanding the mechanisms regulating bone formation and potential targets of countermeasure against decreased bone formation both in astronauts and in general patients with musculoskeletal disorders.

Description: Cosmic rays were discovered in 1911 by the Austrian physicist, Victor Hess. The planet earth is continuously bathed in high-energy galactic cosmic ionizing radiation (GCR), emanating from outside the solar system, and sporadically exposed to bursts of energetic particles from the sun referred to as solar particle events (SPEs). The main source of GCR is believed to be supernovae (exploding stars), while occasionally a disturbance in the sun's atmosphere (solar flare or coronal mass ejection) leads to a surge of radiation particles with sufficient energy to penetrate the earth's magnetic field and enter the atmosphere. The inhabitants of planet earth gain protection from the effects of cosmic radiation from the earth s magnetic field and the atmosphere, as well as from the sun's magnetic field and solar wind. These protective effects extend to the occupants of aircraft flying within the earth s atmosphere, although the effects can be complex for aircraft flying at high altitudes and high latitudes. Travellers in space do not have the benefit of this protection and are exposed to an ionizing radiation field very different in magnitude and quality from the exposure of individuals flying in commercial airliners. The higher amounts and distinct types of radiation qualities in space lead to a large need for understanding the biological effects of space radiation. It is recognized that although there are many overlaps between the aviation and the space environments, there are large differences in radiation dosimetry, risks and protection for airline crew members, passengers and astronauts. These differences impact the application of radiation protection principles of risk justification, limitation, and the principle of as low as reasonably achievable (ALARA). This chapter accordingly is divided into three major sections, the first dealing with the basic physics and health risks, the second with the commercial airline experience, and the third with the aspects of cosmic radiation appertaining to space travel including future considerations.

Description: As logistical access for in-flight space research becomes more limited, the use of ground based spaceflight analogs for life science studies will increase. These studies are particularly important as NASA progresses towards the Lunar and eventually Mars missions outlined in the 2005 Vision for Space Exploration. Countermeasures must be developed to mitigate the clinical risks associated with exploration class space missions. In an effort to coordinate studies across multiple disciplines, NASA has selected 90-day bed rest as the analog of choice, and initiated the Flight Analogs Project to implement research studies with or without the evaluation of countermeasures. Although bed rest is not the analog of choice to evaluate spaceflight-associated immune dysfunction, a standard Immune Assessment was developed for subjects participating in the 90-day bed best studies. The Immune Assessment consists of: leukocyte subset distribution, T cell functional responses, intracellular cytokine production profiles, latent viral reactivation, virus specific T cell levels, virus specific T cell function, stress hormone levels and a behavioral assessment using stress questionnaires. The purpose of the assessment during the initial studies (without countermeasure) is to establish control data against which future studies (with countermeasure) will be evaluated. It is believed that some of the countermeasures planned to be evaluated in future studies, such as exercise, pharmacologic intervention or nutritional supplementation, have the ability to impact immune function. Therefore immunity will likely be monitored during those studies. The data generated during the first three control studies showed that the subjects in general did not display altered peripheral leukocyte subsets, constitutive immune activation, significant latent viral reactivation (EBV, VZV) or altered T cell function. Interestingly, for some subjects the level of constitutively activated T cells (CD8+/CD69+) and virus-specific T cells (CMV and EBV) both decreased during the studies. This likely reflects the isolation of the subjects (from an immunological perspective) and absence of everyday subclinical challenges to the immune system. Cortisol levels (plasma and saliva) did not vary significantly during the studies. This probably reflects a lack of physiological stress during the study and the stress of readaptation to the 1xG environment at R+1. These data demonstrate the absence of significant immune alteration during 90-day bed rest, and establish control data against which future studies (including countermeasures) may be compared.

Description: The purpose of this investigation was to determine if increasing body mass while maintaining bodyweight would affect ground reaction forces and joint kinetics during walking and running. It was hypothesized that performing gait with increased mass while maintaining body weight would result in greater ground reaction forces, and would affect the net joint torques and work at the ankle, knee and hip when compared to gait with normal mass and bodyweight. Vertical ground reaction force was measured for ten subjects (5M/5F) during walking (1.34 m/s) and running (3.13 m/s) on a treadmill. Subjects completed one minute of locomotion at normal mass and bodyweight and at four added mass (AM) conditions (10%, 20%, 30% and 40% of body mass) in random order. Three-dimensional joint position data were collected via videography. Walking and running were analyzed separately. The addition of mass resulted in several effects. Peak impact forces and loading rates increased during walking, but decreased during running. Peak propulsive forces decreased during walking and did not change during running. Stride time increased and hip extensor angular impulse and positive work increased as mass was added for both styles of locomotion. Work increased at a greater rate during running than walking. The adaptations to additional mass that occur during walking are different than during running. Increasing mass during exercise in microgravity may be beneficial to increasing ground reaction forces during walking and strengthening hip musculature during both walking and running. Future study in true microgravity is required to determine if the adaptations found would be similar in a weightless environment.

Description: Background: A previous study has shown that analysis of high-frequency QRS components (HF-QRS) is highly sensitive and reasonably specific for detecting reversible perfusion defects on myocardial perfusion imaging (MPI) scans during adenosine. The purpose of the present study was to try to reproduce those findings. Methods: 12-lead high-resolution electrocardiogram recordings were obtained from 100 patients before (baseline) and during adenosine Tc-99m-tetrofosmin MPI tests. HF-QRS were analyzed regarding morphology and changes in root mean square (RMS) voltages from before the adenosine infusion to peak infusion. Results: The best area under the curve (AUC) was found in supine patients (AUC=0.736) in a combination of morphology and RMS changes. None of the measurements, however, were statistically better than tossing a coin (AUC=0.5). Conclusion: Analysis of HF-QRS was not significantly better than tossing a coin for determining reversible perfusion defects on MPI scans.

Description: The Respiratory Support Pack (RSP) is a medical pack onboard the International Space Station (ISS) that contains much of the necessary equipment for providing aid to a conscious or unconscious crewmember in respiratory distress. Inside the RSP lid pocket is a 5.5 by 11 inch paper procedural cue card, which is used by a Crew Medical Officer (CMO) to set up the equipment and deliver oxygen to a crewmember. In training, crewmembers expressed concerns about the readability and usability of the cue card; consequently, updating the cue card was prioritized as an activity to be completed. The Usability Testing and Analysis Facility at the Johnson Space Center (JSC) evaluated the original layout of the cue card, and proposed several new cue card designs based on human factors principles. The approach taken for the assessment was an iterative process. First, in order to completely understand the issues with the RSP cue card, crewmember post training comments regarding the RSP cue card were taken into consideration. Over the course of the iterative process, the procedural information was reorganized into a linear flow after the removal of irrelevant (non-emergency) content. Pictures, color coding, and borders were added to highlight key components in the RSP to aid in quickly identifying those components. There were minimal changes to the actual text content. Three studies were conducted using non-medically trained JSC personnel (total of 34 participants). Non-medically trained personnel participated in order to approximate a scenario of limited CMO exposure to the RSP equipment and training (which can occur six months prior to the mission). In each study, participants were asked to perform two respiratory distress scenarios using one of the cue card designs to simulate resuscitation (using a mannequin along with the hardware). Procedure completion time, errors, and subjective ratings were recorded. The last iteration of the cue card featured a schematic of the RSP, colors, borders, and simplification of the flow of information. The time to complete the RSP procedure was reduced by approximately three minutes with the new design. In an emergency situation, three minutes significantly increases the probability of saving a life. In addition, participants showed the highest preference for this design. The results of the studies and the new design were presented to a focus group of astronauts, flight surgeons, medical trainers, and procedures personnel. The final cue card was presented to a medical control board and approved for flight. The revised RSP cue card is currently onboard ISS.

Description: A case study of a medical emergency aboard the International Space Station is reviewed. The case involves a female crewmember who is experiencing acute abdominal pain. The interplay of the Crew Medical Officer (CMO) and the NASA Flight Surgeon is given. Possible diagnoses, and advised medical actions are reviewed. Along the case study questions are posed to the reader, and at the end answers are given.

Description: A comprehensive analysis of both the molecular genetic and phenotypic responses of any organism to the spaceflight environment has never been accomplished due to significant technological and logistical hurdles. Moreover, the effects of spaceflight on microbial pathogenicity and associated infectious disease risks have not been studied. The bacterial pathogen Salmonella typhimurium was grown aboard Space Shuttle mission STS-115 and compared to identical ground control cultures. Global microarray and proteomic analyses revealed 167 transcripts and 73 proteins changed expression with the conserved RNA-binding protein Hfq identified as a likely global regulator involved in the response to this environment. Hfq involvement was confirmed with a ground based microgravity culture model. Spaceflight samples exhibited enhanced virulence in a murine infection model and extracellular matrix accumulation consistent with a biofilm. Strategies to target Hfq and related regulators could potentially decrease infectious disease risks during spaceflight missions and provide novel therapeutic options on Earth.

Description: Malnutrition, either by insufficient supply of some nutrients or by overfeeding has a profound effect on the health of an organism. Therefore, optimal nutrition is mandatory on Earth (1 g), in microgravity and also when applying artificial gravity to the human system. Immobilization like in microgravity or bed rest also has a profound effect on different physiological systems, like body fluid regulation, the cardiovascular, the musculoskeletal, the immunological system and others. Up to now there is no countermeasure available which is effective to counteract cardiovascular deconditioning (rf. Chapter 5) together with maintenance of the musculoskeletal system in a rather short period of time. Gravity seems therefore to be one of the main stimuli to keep these systems and application of certain duration of artificial gravity per day by centrifugation has often been proposed as a very potential countermeasure against the weakening of the physiological systems. Up to now, neither optimal intensity nor optimal length of application of artificial gravity has been studied sufficiently to recommend a certain, effective and efficient protocol. However, as shown in chapter 5 on cardiovascular system, in chapter 6 on the neuromuscular system and chapter 7 (bone and connective system) artificial gravity has a very high potential to counteract any degradation caused by immobilization. But, nutrient supply -which ideally should match the actual needs- will interact with these changes and therefore has also to be taken into account. It is well known that astronauts beside the Skylab missions- were and are still not optimally nourished during their stay in space (Bourland et al. 2000;Heer et al. 1995;Heer et al. 2000b;Smith et al. 1997;Smith & Lane 1999;Smith et al. 2001;Smith et al. 2005). It has also been described anecdotally that astronauts have lower appetites. One possible explanation could be altered taste and smell sensations during space flight, although in some early space flights no significant changes were found (Heidelbaugh et al. 1968;Watt et al. 1985). However, data from a recent head-down bed rest study showed significant decrease in smell sensation (Enck et al. unpublished data) suggesting that fluid shifts might have an impact. If this holds true and which has to be validated in further studies, this seems to play an important role for lowered food intake causing insufficient energy intake and subsequently insufficient supply of most of the macro- and micronutrients. Other nutrients are taken in excess, for example sodium. As it is very well known from daily food consumption especially premanufactured food with high salt content seems to be more palatable than that with low salt content. Salt also functions as preservation which is very important taking into account the space food system limitations (i.e., lack of refrigerators and freezers). The preference for food with high salt intake by astronauts might therefore very likely be caused by altered smell and taste sensations in microgravity.

Description: Toxicology dates to the very earliest history of humanity with various poisons and venom being recognized as a method of hunting or waging war with the earliest documentation in the Evers papyrus (circa 1500 BCE). The Greeks identified specific poisons such as hemlock, a method of state execution, and the Greek word toxos (arrow) became the root of our modern science. The first scientific approach to the understanding of poisons and toxicology was the work during the late middle ages of Paracelsus. He formulated what were then revolutionary views that a specific toxic agent or "toxicon" caused specific dose-related effects. His principles have established the basis of modern pharmacology and toxicology. In 1700, Bernardo Ramazzini published the book De Morbis Artificum Diatriba (The Diseases of Workers) describing specific illnesses associated with certain labor, particularly metal workers exposed to mercury, lead, arsenic, and rock dust. Modern toxicology dates from development of the modern industrial chemical processes, the earliest involving an analytical method for arsenic by Marsh in 1836. Industrial organic chemicals were synthesized in the late 1800 s along with anesthetics and disinfectants. In 1908, Hamilton began the long study of occupational toxicology issues, and by WW I the scientific use of toxicants saw Haber creating war gases and defining time-dosage relationships that are used even today.

Description: The addition of inertia to exercising astronauts could increase ground reaction forces and potentially provide a greater health benefit. However, conflicting results have been reported regarding the adaptations to additional mass (inertia) without additional net weight (gravitational force) during locomotion. We examined the effect of increasing inertia while maintaining net gravitational force on vertical ground reaction forces and kinematics during walking and running. Vertical ground reaction force was measured for ten healthy adults (5 male/5 female) during walking (1.34 m/s) and running (3.13 m/s) using a force-measuring treadmill. Subjects completed locomotion at normal weight and mass, and at 10, 20, 30, and 40% of added inertial force. The added gravitational force was relieved with overhead suspension, so that the net force between the subject and treadmill at rest remained equal to 100% body weight. Peak vertical impact forces and loading rates increased with increased inertia during walking, and decreased during running. As inertia increased, peak vertical propulsive forces decreased during walking and did not change during running. Stride time increased during walking and running, and contact time increased during running. Vertical ground reaction force production and adaptations in gait kinematics were different between walking and running. The increased inertial forces were utilized independently from gravitational forces by the motor control system when determining coordination strategies.

Description: Medical requirements for the future Crew Exploration Vehicle (CEV), Lunar Surface Access Module (LSAM), advanced Extravehicular Activity (EVA) suits and Lunar habitat are currently being developed. Crews returning to the lunar surface will construct the lunar habitat and conduct scientific research. Inherent in aggressive surface activities is the potential risk of injury to crewmembers. Physiological responses and the operational environment for short forays during the Apollo lunar missions were studied and documented. Little is known about the operational environment in which crews will live and work and the hardware will be used for long-duration lunar surface operations. Additional information is needed regarding productivity and the events that affect crew function such as a compressed timeline. The Space Medicine Division at the NASA Johnson Space Center (JSC) requested a study in December 2005 to identify Apollo mission issues relevant to medical operations that had impact to crew health and/or performance. The operationally oriented goals of this project were to develop or modify medical requirements for new exploration vehicles and habitats, create a centralized database for future access, and share relevant Apollo information with the multiple entities at NASA and abroad participating in the exploration effort.

Description: Thermoregulation in the space environment is critical for survival, especially in off- nominal operations. In such cases, mathematical models of thermoregulation are frequently employed to evaluate safety-of-flight issues in various human mission scenarious. In this study, the 225-node Wissler model and the 41-Node Metabolic Man model are employed to evaluate the effects of such a scenario. Metabolic loads on astronauts wearing the advanced crew escape suit (ACES) and liquid cooled ventilation garment (LCVG) are imposed on astronauts exposed to elevated cabin temperatures resulting from a systems failure. The study indicates that the performance of the ACES/LCVG cooling system is marginal. Increases in workload and or cabin temperature above nominal will increase rectal temperature, stored heat load, heart rate, and sweating, which could lead to deficits in the performance of cognitive and motor tasks. This is of concern as the ACES/LCVG is employed during Shuttle decent when the likelihood of a safe landing may be compromised. The study indicates that the most effective mitigation strategy would be to decrease the LCVG inlet temperature.

Description: Aerobic deconditioning occurs during long duration space flight despite the use of exercise countermeasures (Convertino, 1996). As a part of International Space Station (ISS) medical operations, periodic tests designed to estimate aerobic capacity are performed to track changes in aerobic fitness and to determine the effectiveness of exercise countermeasures. These tests are performed prior to, during, and after missions of greater than 30 days in duration. Crewmembers selected for missions aboard the ISS perform a graded exercise test on a cycle ergometer approximately 270 days prior to their scheduled launch date in order to measure peak oxygen consumption (VO2PK) and peak heart rate (HRpk). Approximately 30 to 45 days prior to launch, crewmembers perform a submaximal cycle ergometer test at work rates set to elicit 25, 50 and 75% of their pre-flight VO2PK. This test, known as the Periodic Fitness Evaluation (PFE), serves as a baseline measure to which subsequent in-and post-flight exercise tests are compared. While onboard the ISS, crewmembers are normally scheduled to perform the PFE beginning with flight day (FD) 14 and every 30 days thereafter. The PFE is also conducted 5 and 30 days following flight. Using PFE data, aerobic fitness is estimated by quantifying the VO2 vs. HR relationship using linear regression and calculating the VO2 that would occur at the crewmember s previously measured HRpk. Currently, for data collected during flight, this technique assumes that the pre- vs. in-flight oxygen consumption per given cycle workload is similar. However, the validity of this assumption is based upon a sparse amount of data collected during the Skylab era (Michel, et al. 1977). The method of using heart rate and cycle ergometer work rates has been used to estimate aerobic fitness in normal gravity (Astrand and Ryhming, 1954; Lee, 1993). Due to spaceflight induced physiological alterations, such as shifts in extracellular fluid (e.g. plasma) volume, this method may not be valid during space flight. In addition, the ergometer onboard ISS is vibration-isolated and moves with the astronaut s application of force into the pedals. The effect of this movement on the VO2 of cycle exercise on ISS has not been quantified.

Description: This viewgraph presentation reviews issues of health care in space. Some of the issues reviewed are: (1) Physiological adaptation to microgravity, partial gravity, (2) Medical events during spaceflight, (3) Space Vehicle and Environmental and Surface Health Risks, (4) Medical Concept of Operations (CONOPS), (4a) Current CONOPS & Medical Hardware for Shuttle (STS) and ISS, (4b) Planned Exploration Medical CONOPS & Hardware needs, (5) Exploration Plans for Lunar Return Mission & Mars, and (6) Developing Medical Support Systems.

Description: The Cumulative Trauma Disorder (CTD) risks for three different tasks using McCauley-Bell and Badiru's (1993) formula based on task, personal, and organizational factors were examined. For the Multi-Layer Insulation (MLI) blanket task, the results showed that the task, personal, and organizational risks were at about the same level. The personal risk factors for this task were evaluated using a hypothetical female employee age 52. For the pizza dough task, it was shown that the organizational risk was particularly high, with task related factors also at quite dangerous levels. On the other hand, there was a very low level of personal risk factors, based on a female age 17. The flow cytometer task was assessed with three different participants, a11 of whom had quite disparate levels of personal risk, which slightly affected the overall CTD risk. This reveals how individual difference variables certainly need to be considered. The task and organizational risks for this task were rated at about the same moderate level. The overall CTD risk averaged across the three participants was .335, indicating some risk. Compruing across the tasks revealed that the pizza dough task created the greatest overall CTD risk by far (.568), with the MLI (.325) and flow cytometer task (.335) having some risk associated with them. Future research should look into different tasks for more of a comparison

Description: Ocular counter-rolling (OCR) induced by whole body tilt in roll has been explored after spaceflight as an indicator of the adaptation of the otolith function to microgravity. It has been claimed that the overall pattern of OCR responses during static body tilt after spaceflight is indicative of a decreased role of the otolith function, but the results of these studies have not been consistent, mostly due to large variations in the OCR within and across individuals. By contrast with static head tilt, off-vertical axis rotation (OVAR) presents the advantage of generating a sinusoidal modulation of OCR, allowing averaged measurements over several cycles, thus improving measurement accuracy. Accordingly, OCR and the sense of roll tilt were evaluated in seven astronauts before and after spaceflight during OVAR at 45 /s in darkness at two angles of tilt (10 and 20 ). There was no significant difference in OCR during OVAR immediately after landing compared to preflight. However, the amplitude of the perceived roll tilt during OVAR was significantly larger immediately postflight, and then returned to control values in the following days. Since the OCR response is predominantly attributed to the shearing force exerted on the utricular macula, the absence of change in OCR postflight suggests that the peripheral otolith organs function normally after short-term spaceflight. However, the increased sense of roll tilt indicates an adaptation in the central processing of gravitational input, presumably related to a re-weigthing of the internal representation of gravitational vertical as a result of adaptation to microgravity.

Description: Microbial monitoring of spacecraft environments provides key information in the assessment of infectious disease risk to the crew. Monitoring aboard the Mir space station and International Space Station (ISS) has provided a tremendous informational baseline to aid in determining the types and concentrations of microorganisms during a mission. Still, current microbial monitoring hardware utilizes culture-based methodology which may not detect many medically significant organisms, such as Legionella pneumophila. We hypothesize that evaluation of the ISS environment using non-culture-based technologies would reveal microorganisms not previously reported in spacecraft, allowing for a more complete health assessment. To achieve this goal, a spaceflight experiment, operationally designated as SWAB, was designed to evaluate the DNA from environmental samples collected from ISS and vehicles destined for ISS. Results from initial samples indicate that the sample collection and return procedures were successful. Analysis of these samples using denaturing gradient gel electrophoresis and targeted PCR primers for fungal contaminants is underway. The current results of SWAB and their implication for in-flight molecular analysis of environmental samples will be discussed.

Description: For nearly 3.5 years, the Volatile Organic Analyzer (VOA) has routinely analyzed the International Space Station (ISS) atmosphere for a target list of approximately 20 volatile organic compounds (VOCs). Additionally, an early prototype of the VOA collected data aboard submarines in two separate trials. Comparison of the data collected on ISS and submarines showed a surprising similarity in the atmospheres of the two environments. Furthermore, in both cases it was demonstrated that the VOA data can detect hardware issues unrelated to crew health. Finally, it was also clear in both operations that the VOA s size and resource consumption were major disadvantages that would restrict its use in the future. The VOA showed the value of measuring VOCs in closed environments, but it had to be shrunk if it was to be considered for future operations in these environments that are characterized by cramped spaces and limited resources. The Sionex Microanalyzer is a fraction of the VOA s size and this instrument seems capable of maintaining or improving upon the analytical performance of the VOA. The two design improvements that led to a smaller, less complex instrument are the Microanalyzer s use of recirculated air as the gas chromatograph s carrier gas and a micromachined detector. Although the VOA s ion mobility spectrometer and the Microanalyzer s differential mobility spectrometer (DMS) are related detector technologies, the DMS was more amenable to micromachining. This paper will present data from the initial assessment of the Microanalyzer. The instrument was challenged with mixtures that simulated the VOCs typically detected in closed-environment atmospheres.

Description: When cells are exposed to radiation, cellular lesions are induced in the DNA including double strand breaks (DSBs), single strand breaks and clustered DNA damage, which if not repaired with high fidelity may lead to detrimental biological consequences. Complex DSBs are induced by ionizing radiation and characterized by the presence of base lesions close to the break termini. They are believed to be one of the major causes of the biological effects of IR. The complexity of DSBs increases with the ionization density of the radiation and these complex DSBs are distinct from the damage induced by sparsely ionizing gamma-radiation. It has been hypothesized that complex DSBs produced by heavy ions in space pose problems to the DNA repair machinery. We have used imm uno-cyto-chemical staining of phosphorylated histone H2AX (gamma-H2AX) foci, as a marker of DSBs. We have investigated the formation and loss of gamma-H2AX foci and RAD51 foci (a protein involved in the homologous recombination pathway) in mammalian cells induced by low fluences of low-LET gamma-radiation and high-LET Fe-56 ions (1GeV/n, 151 keV/micron LET). M059J and M059K cells, which are deficient and proficient in DNA-PK(sub cs) activity respectively, were used to examine the role of DNA-PK(sub cs), a key protein in the non-homologous end joining (NHEJ) pathway of DSB repair, along with HF19 human fibroblasts. Followi ng irradiation with Fe-56 ions the rate of repair was slower in M059J cells compared with that in M059K, indicating a role for DNA-PK(sub cs) in the repair of DSB induced by Fe-56 ions. However a small percentage of DSBs induced are rejoined within 5 h although many DSBs still persist up to 24 h. When RAD51 was examined in M059J/K cells, RAD51 foci are visible 24 hours after irradiation in approximately 40% of M059J cells compared with 〈5% of M059K cells indicating that persistent DSBs or those formed at stalled replication forks recruit RAD51 in DNA-PK(sub cs) deficient cells. Following 1 Gy gamma-radiation the induction of gamma-H2AX foci is similar in M059J and M059K cells. However, the repair rate of DSBs is slower in M059J cells than in M059K as shown previously but faster than seen with DSB induced by 56Fe ions. Vanillin, an inhibitor of DNA-PK(sub cs), reduces significantly the rate of DSB repair in HF19 cells following 1 Gy gamma-radiation but at 0.25 Gy gamma-irradiation the rate of DSB repair is similar in the presence or absence vanillin, thus suggesting the repair of a sub-set of DSBs induced by low dose, low-LET radiation does not require DNA-PK(sub cs). This sub-set of DSBs is formed in lower yield with high LET radiation. T he complexity of DNA DSBs induced by HZE radiation will be discussed in terms of reduced repair efficiency and provide scope to model different sub-classes of DSBs as precursors that may lead to the detrimental health effects of HZE radiation.

Description: During space travel, astronauts are exposed to energetic particles of a complex composition and energy distribution. For the same amount of absorbed dose, these particles can be much more effective than X- or gamma rays in the induction of biological effects, including cell inactivation, genetic mutations, cataracts, and cancer induction. Several of the biological consequences of space radiation exposure have already been observed in astronauts. This presentation will introduce the space radiation environment and discuss its associated health risks. Accurate assessment of the radiation risks and development of respective countermeasures are essential for the success of future exploration missions to the Moon and Mars.

Description: The Space Flight Cognitive Assessment Tool for Windows (WinSCAT) is a medical requirement on the International Space Station, and its purpose is to evaluate cognitive functioning after physical insult (e.g., head trauma, decompression sickness, exposure to toxic gases, medication side effects). The current objective is to assess cognitive functioning in a long duration space mission analog environment where Artificial Gravity is being applied as a countermeasure in a Bed Rest study. Methods: Fifteen male subjects (8 treatment and 7 control) who participated in 21 days of -6 degree head-down bed rest were assessed. Three practice and three baseline WinSCAT test sessions were administered during the pre-bed rest phase of study participation. During the bed rest phase, the WinSCAT test was scheduled every other day, following the centrifuge, for a total of 10 test sessions. (The treatment group received 60 minutes of centrifugation each day during the 21 days of bed rest. The control subjects were strapped to the centrifuge for the same length of time as the treatment group but were not spun.) During the post-bed rest (reconditioning) phase, the test was administered 4 times. Results: Individual differences were found both within and between the treatment and control groups. After controlling for the number of subjects in each group, the treatment group accounted for more off-nominal WinSCAT scores than the control group. Conclusions:There is some preliminary evidence that centrifuge spinning might negatively impact cognitive functioning. However, due to sample size limitations, it cannot be ascertained whether there were significant differences in cognitive performance between the treatment and control groups. If centrifugation had a negative effect on cognitive functioning, consistent decrements would be expected to be found with all treatment subjects across time. Individual differences in underlying cognitive ability and motivation level are other possible explanations for the results found in this study.

Description: We have previously detected VZV in healthy astronauts both during spaceflight and shortly after landing. Herein, we show that VZV shed in seropositive astronauts is infectious. A total of 40 saliva samples were obtained from each of the 3 astronauts. From each astronaut, 14 samples were taken 109 to 133 days before liftoff, 1 sample was taken every day during 12 days in space, and one sample was taken for 14 consecutive days beginning the second day after landing. Quantitative PCR was used to detect VZV DNA in saliva. None of 42 preflight saliva samples contained VZV DNA. VZV DNA was detected in saliva from 2 of 3 astronauts. In 1 astronaut, 6 of 12 samples obtained during space flight contained 120 to 2,500 copies of VZV DNA per ml; after landing, 1250 copies of VZV DNA were present on day 2, 45 copies on day 3, and 110 copies on day 5. All samples taken 6 to 15 days after touchdown were negative for VZV DNA. In the second astronaut, 5 of 12 samples obtained during space flight contained 18 to 650 copies of VZV DNA per ml; after landing, 560 copies of VZV DNA were present in saliva on day 2, 340 copies on day 4, 45 copies on day 5, and 23 copes on day 6. All samples taken 7 to 15 days after touchdown were negative for VZV DNA. Saliva taken 2 to 6 days after landing from all 3 astronauts was cultured on human fetal lung cells. After one subcultivation, a cytopathic effect developed in cultures inoculated with saliva from the two astronauts whose saliva contained VZV DNA. Both PCR and immunostaining identified the isolates to be VZV and not HSV-1. Importantly, the astronaut in whom no VZV was detected had a history of zoster 9 years earlier. It is possible that a boost in cell-mediated immunity to VZV which is known to develop after zoster protected him from subclinical reactivation. The genotype of the two VZV isolates was determined by VZV ORF22-based PCR/sequencing along with FRET-based PCR assays that target specific nucleotide polymorphisms. Both VZV isolates were found to be the European genotype which also contained a rare MspI restriction enodnuclease site in VZV ORF62 at position 107,252. These findings extend our previous demonstration of VZV DNA in saliva of astronauts by showing that infectious VZV is also present. Thus, like HSV-1 and HSV-2, VZV can reactivate and shed infectious virus in the absence of clinical disease.

Description: Dr. Davis' presentation includes a brief overview of space flight and the lessons learned for health care in microgravity. He will describe the development of policy for health care for international crews. He will conclude his remarks with a discussion of an integrated health care system.

Description: The goal of this project was to examine the effects of artificial gravity (2.5 g) on skeletal muscle strength and key anabolic/catabolic markers known to regulate muscle mass. Two groups of subjects were selected for study: 1) a 21 day-bed rest (BR) control (C) group (N=7); and 2) an AG group (N=8), which was exposed to 21 days of bed-rest plus daily 1 hr exposures to AG (2.5 g). This particular experiment was part of an integrated AG Pilot Project sponsored by NASA/Johnson Space Center. The in vivo torque-velocity relationships of the knee extensors and plantar flexors of the ankle were determined pre and post treatment. Also, pre- and post treatment biopsy samples were obtained from both the vastus lateralis and soleus muscles and were used, in part, for a series of analyses on gene expression (mRNA abundance) of key factors implicated in the anabolic versus catabolic state of the muscle. Post/Pre toque-velocity determinations revealed greater decrements in knee extensor performance in the C versus AG group (P less than 0.04). The plantar flexor muscle group of the AG subjects actually demonstrated a net gain in torque-velocity relationship; whereas, in the C group the overall post/pre responses declined (AG vs C; P less than 0.001). Measurements of muscle fiber cross-sectional area (for both muscles) demonstrated a loss of approx. 20% in the C group while no losses were evident in the AG group. RT-PCR analyses of muscle biopsy specimens demonstrated that markers of growth and cytoskeletal integrity (IGF-1, IGF-1 BP4, mechano growth factor, total RNA, and pro-collagen 3a) were higher in the AG group, whereas catabolic markers (myostatin and atrogen) were elevated in the C group. Importantly, these patterns were seen in both muscles. Based on these observations we conclude that paradigms of AG have the potential to maintain the functional, biochemical, and structural homeostasis of skeletal muscle in the face of chronic unloading states. These findings also warrant further studies since it is likely that other robust paradigms of AG that employ various exercise strategies may be more effective in counteracting long duration unloading states as anticipated on the platforms of the Moon and Mars.

Description: The purpose is to assess physical and chemical degradation of select pharmaceutical formulations from the Shuttle and ISS medical kits. Eleven pharmaceuticals dispensed as different dosage forms were selected based on their physical / chemical characteristics and susceptibility to environmental factors such as, temperature, humidity and light sensitivity. When available, ground-controls of the study medications with matching brand and lot numbers were used for comparison. Samples retrieved from flight were stored along with their matching controls in a temperature and humidity controlled environmental chamber. Temperature, humidity, and radiation data from the Shuttle and ISS were retrieved from onboard HOBO U12 Temp/RH Data Loggers, and from passive dosimeters. Physical and chemical analyses of the pharmaceuticals were conducted using validated United States Pharmacopeia (USP) methods. Results indicated degradation of 6 of the 11 formulations returned from space flights. Four formulations, Amoxicillin / Clavulanate, promethazine, sulfamethoxazole / trimethoprim, and ciprofloxacin tablets depicted discoloration after flight. Chemical content analyses using High or Ultra Performance Liquid Chromatography (HPLC / UPLC) methods revealed that dosage forms of Amoxicillin / Clavulanate, promethazine, sulfamethoxazole / trimethoprim, lidocaine, ciprofloxacin and mupirocin contained less than 95% of manufacturer s labeled claim of active drug compound. Shuttle and ISS environments affect stability and shelf life of certain mediations flown on these missions. Data analysis is in progress to examine the effect of specific space flight environmental factors on pharmaceutical stability. The degradation profiles generated from ground studies in analog environments will be useful in establishing predictive shelf-life profiles for medications intended for use during long-term space exploration missions.

Description: In space, astronauts are constantly bombarded with energetic particles. The goal of the National Aeronautics and Space Agency and the NASA Space Radiation Project is to ensure that astronauts can safely live and work in the space radiation environment. The space radiation environment poses both acute and chronic risks to crew health and safety, but unlike some other aspects of space travel, space radiation exposure has clinically relevant implications for the lifetime of the crew. Among the identified radiation risks are cancer, acute and late CNS damage, chronic and degenerative tissue decease, and acute radiation syndrome. The term "safely" means that risks are sufficiently understood such that acceptable limits on mission, post-mission and multi-mission consequences can be defined. The NASA Space Radiation Project strategy has several elements. The first element is to use a peer-reviewed research program to increase our mechanistic knowledge and genetic capabilities to develop tools for individual risk projection, thereby reducing our dependency on epidemiological data and population-based risk assessment. The second element is to use the NASA Space Radiation Laboratory to provide a ground-based facility to study the health effects/mechanisms of damage from space radiation exposure and the development and validation of biological models of risk, as well as methods for extrapolation to human risk. The third element is a risk modeling effort that integrates the results from research efforts into models of human risk to reduce uncertainties in predicting the identified radiation risks. To understand the biological basis for risk, we must also understand the physical aspects of the crew environment. Thus, the fourth element develops computer algorithms to predict radiation transport properties, evaluate integrated shielding technologies and provide design optimization recommendations for the design of human space systems. Understanding the risks and determining methods to mitigate the risks are keys to a successful radiation protection strategy.

Description: High-energy secondary neutrons, produced by the interaction of galactic cosmic rays (GCR) with the atmosphere, spacecraft structure and planetary surfaces, contribute a significant fraction to the dose equivalent radiation measurement in crew members and passengers of commercial aviation travel as well as astronauts in space missions. The Los Alamos Nuclear Science Center (LANSCE) neutron facility's 30L beam line (4FP30L-A/ICE House) is known to generate neutrons that simulate the secondary neutron spectrum of the Earth's atmosphere at high altitude. The neutron spectrum is also similar to that measured onboard spacecrafts like the MIR and the International Space Station (ISS). To evaluate the biological damage, we exposed human epithelial cells in vitro to the LANSCE neutron beams with an entrance dose rate of 2.5 cGy/hr, and studied the induction of chromosome aberrations that were identified with multicolor-banding in situ hybridization (mBAND) technique. With this technique, individually painted chromosomal bands on one chromosome allowed the identification of inter-chromosomal aberrations (translocation to unpainted chromosomes) and intra-chromosomal aberrations (inversions and deletions within a single painted chromosome). Compared to our previous results with gamma-rays and 600 MeV/nucleon Fe ions of high dose rate at NSRL (NASA Space Radiation Laboratory at Brookhaven National Laboratory), the neutron data from the LANSCE experiments showed significantly higher frequency of chromosome aberrations. However, detailed analysis of the inversion type revealed that all of the three radiation types in the study induced a low incidence of simple inversions. Most of the inversions in gamma-ray irradiated samples were accompanied by other types of intrachromosomal aberrations but few inversions were accompanied by interchromosomal aberrations. In contrast, neutrons and Fe ions induced a significant fraction of inversions that involved complex rearrangements of both inter- and intrachromosome exchanges. The distribution of damage sites on chromosome 3 was also compared for different radiation types. The breakpoints were randomly localized on chromosome 3 with neutrons and Fe ions exposure, whereas non-random distribution with clustering breakpoints was observed with gamma-rays exposure. The specific fingerprint of neutron radiations on chromosomal aberrations will be discussed.

Description: Purpose: Scopolamine is the preferred treatment for motion sickness during space flight because of its quick onset of action, short half-life and favorable side-effect profile. The dose administered depends on the mode of administration and usually ranges between 0.1 and 0.8 mg. Such small doses make it difficult to detect concentrations of scopolamine in biological fluids by using conventional HPLC methods. To measure scopolamine in saliva and thereby to evaluate the pharmacokinetics of scopolamine, we developed an LC/MS/MS method using off-line solid phase extraction. Method: Samples (0.5mL) were loaded onto Waters Oasis HLB co-polymer cartridges (10 mg, 1 mL) and eluted with 0.5 mL methanol without evaporation and reconstitution. HPLC separation of the eluted sample was performed using an Agilent Zorbax SB-CN column (50 x 2.1 mm) at a flow rate of 0.2 mL/min for 4 minutes. The mobile phase for separation was 90:10 (v/v) methanol: ammonium acetate (2 mM) in water, pH 5.0 +/- 0.1. Concentrations of scopolamine were determined using a Micromass Quattro Micro(TM) mass spectrometer with electrospray ionization (ESI). ESI mass spectra were acquired in positive ion mode with multiple reaction monitoring for the determination of scopolamine m/z = 304.2 yields 138.1 and internal standard (IS) hyoscyamine m/z = 290.2 yields 124.1. Results: The method is rapid, reproducible, specific and has the following parameters: scopolamine and the IS are eluted at 1.7 and 3.2 min respectively. The linear range is 50-5000 pg/mL for scopolamine in saliva with correlation coefficients 〉 0.99 with a CV 〈 0.5 %. The intra-day and inter-day CVs are 〈 15 % for quality control samples with concentrations of 75, 300, 750 and 3000 pg/mL of scopolamine in human saliva. Conclusion: Solid phase extraction allows more rapid sample preparation and greater precision than liquid extraction. Furthermore, we increased the sensitivity and specificity by adjusting the LC mobile phase and using an MS/MS detector.

Description: The vestibular function and tracking eye movements were investigated in 12 Russian crew members of ISS missions on days 1(2), 4(5-6), and 8(9-10) after prolonged exposure to microgravity (126 to 195 days). The spontaneous oculomotor activity, static torsional otolith-cervico-ocular reflex, dynamic vestibulo-cervico-ocular responses, vestibular reactivity, tracking eye movements, and gaze-holding were studied using videooculography (VOG) and electrooculography (EOG) for parallel eye movement recording. On post-flight days 1-2 (R+1-2) some cosmonauts demonstrated: - an increased spontaneous oculomotor activity (floating eye movements, spontaneous nystagmus of the typical and atypical form, square wave jerks, gaze nystagmus) with the head held in the vertical position; - suppressed otolith function (absent or reduced by one half amplitude of torsional compensatory eye counter-rolling) with the head inclined statically right- or leftward by 300; - increased vestibular reactivity (lowered threshold and increased intensity of the vestibular nystagmus) during head turns around the longitudinal body axis at 0.125 Hz; - a significant change in the accuracy, velocity, and temporal characteristics of the eye tracking. The pattern, depth, dynamics, and velocity of the vestibular function and tracking eye movements recovery varied with individual participants in the investigation. However, there were also regular responses during readaptation to the normal gravity: - suppression of the otolith function was typically accompanied by an exaggerated vestibular reactivity; - the structure of visual tracking (the accuracy of fixational eye rotations, smooth tracking, and gaze-holding) was disturbed (the appearance of correcting saccades, the transition of smooth tracking to saccadic tracking) only in those cosmonauts who, in parallel to an increased reactivity of the vestibular input, also had central changes in the oculomotor system (spontaneous nystagmus, gaze nystagmus).

Description: NASA is developing a systems biology approach to improve the assessment of health risks associated with space radiation. The primary toxic and mutagenic lesion following radiation exposure is the DNA double strand break (DSB), thus a model incorporating proteins and pathways important in response and repair of this lesion is critical. One key protein heterodimer for systems models of radiation effects is the Ku(sub 70/80) complex. The Ku70/80 complex is important in the initial binding of DSB ends following DNA damage, and is a component of nonhomologous end joining repair, the primary pathway for DSB repair in mammalian cells. The C-terminal domain of Ku70 (Ku70c, residues 559-609), contains an helix-extended strand-helix motif and similar motifs have been found in other nucleic acid-binding proteins critical for DNA repair. However, the exact mechanism of damage recognition and substrate specificity for the Ku heterodimer remains unclear in part due to the absence of a high-resolution structure of the Ku70c/DNA complex. We performed a series of molecular dynamics (MD) simulations on a system with the subunit Ku70c and a 14 base pairs DNA duplex, whose starting structures are designed to be variable so as to mimic their different binding modes. By analyzing conformational changes and energetic properties of the complex during MD simulations, we found that interactions are preferred at DNA ends, and within the major groove, which is consistent with previous experimental investigations. In addition, the results indicate that cooperation of Ku70c with other subunits of Ku(sub 70/80) is necessary to explain the high affinity of binding as observed in experiments.

Description: The Habitability & Environmental Factors and Space Medicine Divisions have developed the Space Flight Human System Standard (SFHSS) (NASA-STD-3001) to replace NASA-STD-3000 as a new NASA standard for all human spaceflight programs. The SFHSS is composed of 2 volumes. Volume 1, Crew Health, contains medical levels of care, permissible exposure limits, and fitness for duty criteria, and permissible outcome limits as a means of defining successful operating criteria for the human system. Volume 2, Habitability and Environmental Health, contains environmental, habitability and human factors standards. Development of the Human Integration Design Handbook (HIDH), a companion to the standard, is currently under construction and entails the update and revision of NASA-STD-3000 data. This new handbook will, in the fashion of NASA STD-3000, assist engineers and designers in appropriately applying habitability, environmental and human factors principles to spacecraft design. Organized in a chapter-module-element structure, the HIDH will provide the guidance for the development of requirements, design considerations, lessons learned, example solutions, background research, and assist in the identification of gaps and research needs in the disciplines. Subject matter experts have been and continue to be solicited to participate in the update of the chapters. The purpose is to build the HIDH with the best and latest data, and provide a broad representation from experts in industry, academia, the military and the space program. The handbook and the two standards volumes work together in a unique way to achieve the required level of human-system interface. All new NASA programs will be required to meet Volumes 1 and 2. Volume 2 presents human interface goals in broad, non-verifiable standards. Volume 2 also requires that each new development program prepare a set of program-specific human factors requirements. These program-specific human and environmental factors requirements must be verifiable and tailored to assure the new system meets the Volume 2 standards. Programs will use the HIDH to write their verifiable program-specific requirements.

Description: The artificial gravity pilot project was designed to investigate the efficacy of daily exposure to a Gz acceleration gradient for counteracting the physiologic decrements induced by prolonged bed rest. A short radius centrifuge was used to produce a Gz gradient such that 1 g was applied at the level of the subject s heart and 2.5 g at the feet. For inclusion in the study, subjects were required to complete a 75-minute screening spin on the centrifuge. During the study, each active treatment subject was scheduled for a 60-minute spin each day for 20 consecutive days. During centrifugation, subjects were continuously monitored by a physician for signs and symptoms of pre-syncope, motion sickness, arrhythmias, joint/muscle pain and any other unanticipated problems. The physician was also present to provide emergency care in the case of a medical emergency. Cameras mounted on the centrifuge were used to provide a means of observing the subject s face and torso. Audio communication was continuously maintained. Other monitoring tools included two-lead EKG tracings, pulse oximetry, intermittent sphygmomanometer readings, lights in the peripheral visual field, and continuous blood pressure readout from a tonometry device. Thirty screening runs were attempted using twenty-seven subjects. Seven of these runs were terminated early for symptoms of pre-syncope, motion sickness, or GI distress. A total of eight subjects completed the active treatment arm of the study. Of the 160 centrifuge runs that were scheduled for these eight treatment subjects, 152 were completed, seven were terminated early, and one was not attempted. Of the seven early terminations, four were related to symptoms of pre-syncope, one to leg pain, one to GI discomfort, and one to equipment failure. Three terminations for adverse symptoms occurred on the first treatment day. Three terminations occurred on day nineteen of treatment and within 24 hours after scheduled soleus and quadriceps muscle biopsies. We have summarized the relative usefulness of the information obtained by the various monitoring modalities in making a decision to terminate a centrifuge run. The video and audio communication information was essential to the decision-making process. Heart rate and EKG tracings are considered valuable, even though no spins were terminated due to significant arrhythmias. The tonometer device was generally not reliable in this application. Our observations suggest that subjects may be less tolerant of centrifugation just after starting bed rest and after invasive procedures.

Description: The IMAG Pilot Study, recently completed at the University of Texas Medical Branch, filled in the second major gap in knowledge standing in the way of development of a practical Short Radius Centrifuge (SRC) and the use of Artificial Gravity (AG) as a multi-system countermeasure to combat the deconditioning associated with extended weightlessness. (The first challenge, to adapt rapidly rotating subjects to permit unlimited head movements without excessive motion sickness, was achieved in a series of studies at MIT involving incremental increases in head and centrifuge velocity.) It remained to be demonstrated that intermittent exposure to AG, at only one hour per day for 21 days, would have any positive effect on slowing or eliminating of deconditioning. Bed-rested normal subjects were used as a ground analog for astronauts in weightlessness. The results are clearly positive for the key physiological systems of interest: cardiovascular, muscle, and bone. No functionally relevant changes were observed in immune, cognitive, or sensory-motor function. Furthermore, we found that our initial concerns about the inability of deconditioned subjects to withstand daily centrifugation without syncope were misplaced. These encouraging initial results clearly support the further development of AG protocols. We recommend, as the next steps, the integration of a controlled exercise device on the SRC to determine the synergy between AG and exercise. Coupled with appropriate exercise device(s) the AG protocol will be tuned to-ward an optimal prescription for minimum exposure duration and frequency, maximum AG level and SRC speed.. Performance of these next steps will require extensive use of bed-rest/centrifuge facilities and eventually validation using an SRC in space. A space SRC could be placed in the ISS or on a planetary surface.

Description: Astronauts often use promethazine (PMZ) to counteract space motion sickness; however PMZ may cause drowsiness, which might impair cognitive function. In a NASA ground study, subjects received PMZ and their cognitive performance was then monitored over time. Subjects also reported sleepiness using the Karolinska Sleepiness Score (KSS), which ranges from 1 - 9. A problem arises when using KSS to establish an association between true sleepiness and performance because KSS scores tend to overly concentrate on the values 3 (fairly awake) and 7 (moderately tired). Therefore, we defined a latent sleepiness measure as a continuous random variable describing a subject s actual, but unobserved true state of sleepiness through time. The latent sleepiness and observed KSS are associated through a conditional probability model, which when coupled with demographic factors, predicts performance.

Description: Decompression sickness (DCS) is multivariable. But we hypothesize an aerobically fit person is less likely to experience hypobaric DCS than an unfit person given that fitness is exploited as part of the denitrogenation (prebreathe, PB) process prior to an altitude exposure. Aerobic fitness is peak oxygen uptake (VO2pk, ml/kg/min). METHODS: Treadmill or cycle protocols were used over 15 years to determine VO2pks. We evaluated dichotomous DCS outcome and venous gas emboli (VGE) outcome detected in the pulmonary artery with Doppler ultrasound associated with VO2pk for two classes of experiments: 1) those with no PB or PB under resting conditions prior to ascent in an altitude chamber, and 2) PB that included exercise for some part of the PB. There were 165 exposures (mean VO2pk 40.5 +/- 7.6 SD) with 25 cases of DCS in the first protocol class and 172 exposures (mean VO2pk 41.4 +/- 7.2 SD) with 25 cases of DCS in the second. Similar incidence of the DCS (15.2% vs. 14.5%) and VGE (45.5% vs. 44.8%) between the two classes indicates that decompression stress was similar. The strength of association between outcome and VO2pk was evaluated using univariate logistic regression. RESULTS: An inverse relationship between the DCS outcome and VO2pk was evident, but the relationship was strongest when exercise was done as part of the PB (exercise PB, coef. = -0.058, p = 0.07; rest or no PB, coef. = -0.005, p = 0.86). There was no relationship between VGE outcome and VO2pk (exercise PB, coef. = -0.003, p = 0.89; rest or no PB, coef. = 0.014, p = 0.50). CONCLUSIONS: A significant change in probability of DCS was associated with fitness only when exercise was included in the denitrogenation process. We believe a fit person that exercises during PB efficiently eliminates dissolved nitrogen from tissues.

Description: From dealing with the inherent uncertainties in outcomes of scientific research to the lack of applicability of current NASA Procedural Requirements guidance documentation, research-based projects present challenges that require unique application of classical project management techniques. If additionally challenged by the creation of a new program transitioning from basic to applied research in a technical environment often unfamiliar with the cost and schedule constraints addressed by project management practices, such projects can find themselves struggling throughout their life cycles. Finally, supplying deliverables to a prime vehicle customer, also in the formative stage, adds further complexity to the development and management of research-based projects. The Biomedical Research and Countermeasures Projects Branch at NASA Johnson Space Center encompasses several diverse applied research-based or research-enabling projects within the newly-formed Human Research Program. This presentation will provide a brief overview of the organizational structure and environment in which these projects operate and how the projects coordinate to address and manage technical requirements. We will identify several of the challenges (cost, technical, schedule, and personnel) encountered by projects across the Branch, present case reports of actions taken and techniques implemented to deal with these challenges, and then close the session with an open forum discussion of remaining challenges and potential mitigations.

Description: Efficient, effective, multi-system countermeasures will likely be required to protect the health, safety, and performance of crews aboard planned exploration-class space flight missions to Mars and beyond. To that end, NASA, DLR, and IMBP initiated a multi-center international project to begin systematically exploring the utility of artificial gravity (AG) as a multi-system countermeasure in ground based venues using test subjects deconditioned by bed rest. The goal of this project is to explore the efficacy of short-radius, intermittent AG as a countermeasure to bone, muscle, cardiovascular, and sensory-motor adaptations to hypogravity. This session reports the results from a pilot study commissioned to validate a standardized protocol to be used by all centers involved in the project. Subject selection criteria, medical monitoring requirements, medical care procedures, experiment control procedures, and standardized dependent measures were established jointly. Testing was performed on 15 rigorously screened male volunteers subjected to 21 days of 6deg HDT bed rest. (All provided written consent to volunteer after the nature of the study and its hazards were clearly explained to them.) Eight were treated with daily 1hr AG exposures (2.5g at the feet decreasing to 1.0g at the heart) aboard a short radius (3m) centrifuge, while the other seven served as controls. Multiple tests of multiple dependent measures were made in each of the primary physiological systems of interest during a 10 day acclimatization period prior to HDT bed rest and again during an 8 day recovery period after the bed rest period was complete. Analyses of these data (presented in other papers in this session) suggest the AG prescription had salutary effects on aspects of the bone, muscle, and cardiovascular systems, with no untoward effects on the vestibular system, the immune system, or cognitive function. Furthermore, treatment subjects were able to tolerate 153/160 centrifuge sessions over the 21 day deconditioning protocol, suggesting that tolerance was unaffected by deconditioning. These positive results set the stage for full implementation of the planned multi-center international AG project. Future work will be devoted to developing optimization techniques for AG prescriptions (likely supplemented by exercise) to provide maximum physiological protection across all systems subject to space flight deconditioning in both men and women with minimum time and/or side effects. While a continuous AG solution (rotating vehicle) would likely be more efficient, this study suggests that intermittent AG could be an effective multi-system countermeasure.

Description: In preparation for the NASA Artificial Gravity (AG) pilot study, the tolerability of the proposed AG parameters was tested in 11 ambulatory human subjects (6m, 5w) by exposing each to a short arm centrifuge trial. Subjects were oriented in the supine position (but inclined 6deg head down) on one arm of the centrifuge, and the rotation rate (30.6-33.4 rpm) and radial position of the feet were set to produce 2.5G of equivalent gravitational load at the force plate directly beneath the feet, 1G at the level of the mediastinum, and approximately 0.55G at the labyrinth. Amongst the 6 men participating in this preliminary study, 5 completed at least 60 minutes of the trial successfully with no adverse sequelae. However, amongst the female cohort the test was stopped by the medical monitor before 60 min in all but one case, with pre-syncope listed as the reason for termination in all cases. Mean time before abort of the centrifuge run amongst the women was 33.2 +/- 20.97 min. It is known that women have a greater predisposition to syncope during orthostatic stress, under normal tilt table conditions, during LBNP, and following space flight. The reasons for this difference are the subject of some debate, but anthropometric factors, the vasoactive effects of sex hormones, gender differences in susceptibility to motion sickness, catecholamine levels, ability to augment total peripheral resistance in response to orthostatic stress, and structural differences in cardiac anatomy and physiology have all been suggested. This finding led to the exclusion of women from the AG pilot study. Clearly if AG is to be employed as a multi-system countermeasure it must provide physiological protection at rotation rates within the tolerance limits of all potential astronauts. Further investigation of the responses of women to centrifugation will be necessary to determine how to adjust AG parameters for tolerance by female subjects before a more detailed investigation of the appropriate dose in terms of G load, rotation rate, exposure duration and frequency can be performed.

Description: To study the effects of 21 days of head-down bed rest (HDBR), with versus without an artificial gravity (AG) countermeasure, on cardiac autonomic and advanced electrocardiographic function. Fourteen healthy men participated in the study: seven experienced 21 days of HDBR alone ("HDBR controls") and seven the same degree and duration of HDBR but with approximately 1hr daily short-arm centrifugation as an AG countermeasure ("AG-treated"). Five minute supine high-fidelity 12-lead ECGs were obtained in all subjects: 1) 4 days before HDBR; 2) on the last day of HDBR; and 3) 7 days after HDBR. Besides conventional 12-lead ECG intervals and voltages, all of the following advanced ECG parameters were studied: 1) both stochastic (time and frequency domain) and deterministic heart rate variability (HRV); 2) beat-to-beat QT interval variability (QTV); 3) T-wave morphology, including signal-averaged T-wave residua (TWR) and principal component analysis ratios; 4) other SAECG-related parameters including high frequency QRS ECG and late potentials; and 5) several advanced ECG estimates of left ventricular (LV) mass. The most important results by repeated measures ANOVA were that: 1) Heart rates, Bazett-corrected QTc intervals, TWR, LF/HF power and the alpha 1 of HRV were significantly increased in both groups (i.e., by HDBR), but with no relevant HDBR*group differences; 2) All purely "vagally-mediated" parameters of HRV (e.g., RMSSD, HF power, Poincare SD1, etc.), PR intervals, and also several parameters of LV mass (Cornell and Sokolow-Lyon voltages, spatial ventricular activation times, ventricular gradients) were all significantly decreased in both groups (i.e., by HDBR), but again with no relevant HDBR*group differences); 3) All "generalized" or "vagal plus sympathetic" parameters of stochastic HRV (i.e., SDNN, total power, LF power) were significantly more decreased in the AG-treated group than in the HDBR-only group (i.e., here there was a relevant HDBR*group difference); and 4) QTV index was also significantly more changed (increased) in the AG-treated group than in the HDBR-only group, although this was clearly due to a greater decrease in generalized HRV and not to a greater increase in QTV proper because there was no relevant HDBR*group effect for either the SDNN or the RMSSD of QTV. Brief daily AG treatment by short-arm centrifuge during each of 21 days of HDBR does not appear to protect against HDBR-related losses of cardiac autonomic function or of LV mass as estimated by ECG.

Description: Cardiovascular effects of an artificial gravity (AG) countermeasure on deconditioned male volunteers were studied. In two groups of men we measured cardiovascular parameters at rest and in response to 30 minutes of 80 deg. head up tilt (HUT) before, at the end of, and four days following 21 days of 6 deg. head down bed rest (HDBR). One group (N=7) underwent no countermeasure while the other (N=8) received a daily, one hour, dose (2.5 gz at the foot, decreasing to 1.0 gz at the heart) of AG training on the Johnson Space Center short radius centrifuge. Cardiovascular parameters measured included heart rate, blood pressure, stroke volume, cardiac output, peripheral vascular resistance, plasma volume shifts, and vasoactive hormones. Untrained subjects exhibited shorter tilt survival (on average 8 minutes shorter) compared to trained subjects. By the end of bed rest, mean heart rate (MHR) was elevated in both groups (both supine and during tilt). In addition, treated subjects demonstrated lower, tilt-induced, increases in MHR four days following HDBR, indicating a more rapid return to pre bed rest conditions. Results from an index of autonomic balance (percentage of MHR spectral power in the respiratory frequency range) in control of heart rate are consistent with the interpretation that parasympathetic nervous system withdrawal was responsible for both tilt- and bed rest-induced increases in MHR. Our data support our pre-study hypothesis that AG treatment would lessen cardiovascular effects of deconditioning in bed rested men and suggest that AG should be further pursued as a space flight countermeasure.

Description: Conventional saturation decompression protocols use linear decompression rates that become progressively slower at shallower depths, consistent with free gas phase control vs. dissolved gas elimination kinetics. If decompression is limited by control of free gas phase, linear decompression is an inefficient strategy. The NASA prebreathe reduction program demonstrated that exercise during O2 prebreathe resulted in a 50% reduction (2 h vs. 4 h) in the saturation decompression time from 14.7 to 4.3 psi and a significant reduction in decompression sickness (DCS: 0 vs. 23.7%). Combining exercise with intermittent recompression, which controls gas phase growth and eliminates supersaturation before exercising, may enable more efficient saturation decompression schedules. A tissue bubble dynamics model (TBDM) was used in conjunction with a NASA exercise prebreathe model (NEPM) that relates tissue inert gas exchange rate constants to exercise (ml O2/kg-min), to develop a schedule for decompression from helium saturation at 400 fsw. The models provide significant prediction (p 〈 0.001) and goodness of fit with 430 cases of DCS in 6437 laboratory dives for TBDM (p = 0.77) and with 22 cases of DCS in 159 altitude exposures for NEPM (p = 0.70). The models have also been used operationally in over 25,000 dives (TBDM) and 40 spacewalks (NEPM). The standard U.S. Navy (USN) linear saturation decompression schedule from saturation at 400 fsw required 114.5 h with a maximum Bubble Growth Index (BGI(sub max)) of 17.5. Decompression using intermittent recompression combined with two 10 min exercise periods (75% VO2 (sub peak)) per day required 54.25 h (BGI(sub max): 14.7). Combined intermittent recompression and exercise resulted in a theoretical 53% (2.5 day) reduction in decompression time and theoretically lower DCS risk compared to the standard USN decompression schedule. These results warrant future decompression trials to evaluate the efficacy of this approach.

Description: Human presence in space, whether permanent or temporary, is accompanied by the presence of microbes. However, the extent of microbial changes in response to spaceflight conditions and the corresponding changes to infectious disease risk is unclear. Previous studies have indicated that spaceflight weakens the immune system in humans and animals. In addition, preflight and in-flight monitoring of the International Space Station (ISS) and other spacecraft indicates the presence of opportunistic pathogens and the potential of obligate pathogens. Altered antibiotic resistance of microbes in flight has also been shown. As astronauts and cosmonauts live for longer periods in a closed environment, especially one using recycled water and air, there is an increased risk to crewmembers of infectious disease events occurring in-flight. Therefore, understanding how the space environment affects microorganisms and their disease potential is critically important for spaceflight missions and requires further study. The goal of this flight experiment, operationally called MICROBE, is to utilize three model microbial pathogens, Salmonella typhimurium, Pseudomonas aeruginosa, and Candida albicans to examine the global effects of spaceflight on microbial gene expression and virulence attributes. Specifically, the aims are (1) to perform microarray-mediated gene expression profiling of S. typhimurium, P. aeruginosa, and C. albicans, in response to spaceflight in comparison to ground controls and (2) to determine the effect of spaceflight on the virulence potential of these microorganisms immediately following their return from spaceflight using murine models. The model microorganisms were selected as they have been isolated from preflight or in-flight monitoring, represent different degrees of pathogenic behavior, are well characterized, and have sequenced genomes with available microarrays. In particular, extensive studies of S. typhimurium by the Principal Investigator, Dr. Nickerson, using ground-based analog systems demonstrate important changes in the genotypic, phenotypic, and virulence characteristics of this pathogen resulting from exposure to a flight-like environment (i.e. modeled microgravity).

Description: Computerized dynamic posturography (CDP) has become a standard technique for objectively quantifying balance control performance, diagnosing the nature of functional impairments underlying balance disorders, and monitoring clinical treatment outcomes. We have long used CDP protocols to assess recovery of sensory-motor function in astronauts following space flight. The most reliable indicators of post-flight crew performance are the sensory organization tests (SOTs), particularly SOTs 5 and 6, which are sensitive to changes in availability and/or utilization of vestibular cues. We have noted, however, that some astronauts exhibiting obvious signs of balance impairment after flight are able to score within clinical norms on these tests, perhaps as a result of adopting competitive strategies or by their natural skills at substituting alternate sensory information sources. This insensitivity of the CDP protocol could underestimate of the degree of impairment and, perhaps, lead to premature release of those crewmembers to normal duties. To improve the sensitivity of the CDP protocol we have introduced static and dynamic head tilt SOT trials into our protocol. The pattern of postflight recovery quantified by the enhanced CDP protocol appears to more aptly track the re-integration of sensory-motor function, with recovery time increasing as the complexity of sensory-motor/biomechanical task increases. The new CDP protocol therefore seems more suitable for monitoring post-flight sensory-motor recovery and for indicating to crewmembers and flight surgeons fitness for return to duty and/or activities of daily living. There may be classes of patients (e.g., athletes, pilots) having motivation and/or performance characteristics similar to astronauts whose sensory-motor treatment outcomes would also be more accurately monitored using the enhanced CDP protocol. Furthermore, the enhanced protocol may be useful in early detection of age-related balance disorders.

Description: Virtual environments (VE) offer unique training opportunities, particularly for training astronauts and preadapting them to the novel sensory conditions of microgravity. Sensorimotor aftereffects of VEs are often quite similar to adaptive sensorimotor responses observed in astronauts during and/or following space flight. The purpose of this research was to compare disturbances in sensorimotor coordination produced by dome virtual environment display and to examine the effects of exposure duration, and repeated exposures to VR systems. The current study examined disturbances in eye-head-hand (EHH) and eye-head coordination. Preliminary results will be presented. Eleven subjects have participated in the study to date. One training session was completed in order to achieve stable performance on the EHH coordination and VE tasks. Three experimental sessions were performed each separated by one day. Subjects performed a navigation and pick and place task in a dome immersive display VE for 30 or 60 min. The subjects were asked to move objects from one set of 15 pedestals to the other set across a virtual square room through a random pathway as quickly and accurately as possible. EHH coordination was measured before, immediately after, and at 1 hr, 2 hr, 4 hr and 6 hr following exposure to VR. EHH coordination was measured as position errors and reaction time in a pointing task that included multiple horizontal and vertical LED targets. Repeated measures ANOVAs were used to analyze the data. In general, we observed significant increases in position errors for both horizontal and vertical targets. The largest decrements were observed immediately following exposure to VR and showed a fairly rapid recovery across test sessions, but not across days. Subjects generally showed faster RTs across days. Individuals recovered from the detrimental effects of exposure to the VE on position errors within 1-2 hours. The fact that subjects did not significantly improve across days suggests that in order to achieve dual adaptation of EHH coordination may require more than three training sessions. These findings provide some direction for developing training schedules for VE users that facilitate adaptation, support the idea that preflight training of astronauts may serve as useful countermeasure for the sensorimotor effects of space flight, and support the idea that VEs may serve as an analog for sensorimotor effects of spaceflight.

Description: Orthostatic hypotension is a recognized risk for crewmembers returning from space. Numerous cardiovascular mechanisms have been proposed to account for this problem including vascular and cardiac dysfunction. We studied arterial and cardiac function in 6-degree head-down tilt bed rest, which is the most widely accepted ground-based analog of spaceflight. Eleven subjects are included in this study (8 men and 3 women). Data analysis was limited to the first 49 days, and compared to pre-bed rest baseline data. Using ultrasound, data was collected on arterial diameters and flows at baseline and during reactive hyperemia and following administration of nitroglycerin. Echocardiography was used to acquire information regarding systolic and diastolic function as well as ventricular mass and diameter. Plasma volumes were significantly decreased by 7 days of bed rest and stayed down through 49 days. There were no differences in reactive hyperemic response in the arm at any time point. However, the hyperemic response in the leg was significantly increased at day 49. Arterial responses to nitroglycerin did not change over the duration of bed rest (day effect) in either the arm or leg, but there was a significant difference between the arm and the leg responses. There was a marked decrease in anterior tibial intimal-medial thickness at days 21, 35 and 49. Several cardiac functional parameters including IVRT, Mitral e-wave, ejection time, velocity of circumferential shortening and myocardial performance index were significantly changed following 49 days of bed rest. These data show that some cardiovascular measures change during bed rest, while others do not. Further study is needed to determine if these measures can provide any insight into the effects of bed rest, or spaceflight, on human cardiovascular performance.

Description: Space radiation presents major challenges to astronauts on the International Space Station and for future missions to the Earth s moon or Mars. Methods used to project risks on Earth need to be modified because of the large uncertainties in projecting cancer risks from space radiation, and thus impact safety factors. We describe NASA s unique approach to radiation safety that applies uncertainty based criteria within the occupational health program for astronauts: The two terrestrial criteria of a point estimate of maximum acceptable level of risk and application of the principle of As Low As Reasonably Achievable (ALARA) are supplemented by a third requirement that protects against risk projection uncertainties using the upper 95% confidence level (CL) in the radiation cancer projection model. NASA s acceptable level of risk for ISS and their new lunar program have been set at the point-estimate of a 3-percent risk of exposure induced death (REID). Tissue-averaged organ dose-equivalents are combined with age at exposure and gender-dependent risk coefficients to project the cumulative occupational radiation risks incurred by astronauts. The 95% CL criteria in practice is a stronger criterion than ALARA, but not an absolute cut-off as is applied to a point projection of a 3% REID. We describe the most recent astronaut dose limits, and present a historical review of astronaut organ doses estimates from the Mercury through the current ISS program, and future projections for lunar and Mars missions. NASA s 95% CL criteria is linked to a vibrant ground based radiobiology program investigating the radiobiology of high-energy protons and heavy ions. The near-term goal of research is new knowledge leading to the reduction of uncertainties in projection models. Risk projections involve a product of many biological and physical factors, each of which has a differential range of uncertainty due to lack of data and knowledge. The current model for projecting space radiation cancer risk relies on the three assumptions of linearity, additivity, and scaling along with the use of population averages. We describe uncertainty estimates for this model, and new experimental data that sheds light on the accuracy of the underlying assumptions. These methods make it possible to express risk management objectives in terms of quantitative metrics, i.e., the number of days in space without exceeding a given risk level within well defined confidence limits. The resulting methodology is applied to several human space exploration mission scenarios including lunar station, deep space outpost, and a Mars mission. Factors that dominate risk projection uncertainties and application of this approach to assess candidate mitigation approaches are described.

Description: Energetic primary and secondary particles pose a health risk to astronauts in extended ISS and future Lunar and Mars missions. High-LET radiation is much more effective than low-LET radiation in the induction of various biological effects, including cell inactivation, genetic mutations, cataracts and cancer. Most of these biological endpoints are closely correlated to chromosomal damage, which can be utilized as a biomarker for radiation insult. In this study, human epithelial cells were exposed in vitro to gamma rays, 1 GeV/nucleon Fe ions and secondary neutrons whose spectrum is similar to that measured inside the Space Station. Chromosomes were condensed using a premature chromosome condensation technique and chromosome aberrations were analyzed with the multi-color banding (mBAND) technique. With this technique, individually painted chromosomal bands on one chromosome allowed the identification of both interchromosomal (translocation to unpainted chromosomes) and intrachromosomal aberrations (inversions and deletions within a single painted chromosome). Results of the study confirmed the observation of higher incidence of inversions for high-LET irradiation. However, detailed analysis of the inversion type revealed that all of the three radiation types in the study induced a low incidence of simple inversions. Half of the inversions observed in the low-LET irradiated samples were accompanied by other types of intrachromosome aberrations, but few inversions were accompanied by interchromosome aberrations. In contrast, Fe ions induced a significant fraction of inversions that involved complex rearrangements of both the inter- and intrachromosome exchanges.

Description: Protecting crew from ionizing radiation is a key life sciences problem for long-duration space missions. The three major sources/types of radiation are found in space: galactic cosmic rays, trapped Van Allen belt radiation, and solar particle events. All present varying degrees of hazard to crews; however, exposure to high doses of any of these types of radiation ultimately induce both acute and long-term biological effects. High doses of space radiation can lead to the development of toxicity associated with the acute radiation syndrome (ARS) which could have significant mission impact, and even render the crew incapable of performing flight duties. The creation of efficient radiation protection technologies is considered an important target in space radiobiology, immunology, biochemistry and pharmacology. Two major mechanisms of cellular, organelle, and molecular destruction as a result of radiation exposure have been identified: 1) damage induced directly by incident radiation on the macromolecules they encounter and 2) radiolysis of water and generation of secondary free radicals and reactive oxygen species (ROS), which induce chemical bond breakage, molecular substitutions, and damage to biological molecules and membranes. Free-radical scavengers and antioxidants, which neutralize the damaging activities of ROS, are effective in reducing the impact of small to moderate doses of radiation. In the case of high doses of radiation, antioxidants alone may be inadequate as a radioprotective therapy. However, it remains a valuable component of a more holistic strategy of prophylaxis and therapy. High doses of radiation directly damage biological molecules and modify chemical bond, resulting in the main pathological processes that drive the development of acute radiation syndromes (ARS). Which of two types of radiation-induced cellular lethality that ultimately develops, apoptosis or necrosis, depends on the spectrum of incident radiation, dose, dose rate, and functional conditions of impacted cells/organisms. The administration of an experimental anti-radiation vaccine may provide an immunologically based, adjunct method of prevention or prophylaxis against clinical ARS. The administration of experimental anti-radiation serum (ARS) and the use of the blood dialysis methods, such as immune plasma-sorption, may assist in the clearance of radiation-specific toxins and may enhance established strategies for the mitigation of the biological effects leading to ARS, and should be evaluated for use on exploration-class space missions.

Description: Introduction: Achieving NASA's Space Exploration Vision scientific objectives will require human access into cratered and uneven terrain for the purpose of sample acquisition to assess geological, and perhaps even biological features and experiments. Operational risk management is critical to safely conduct the anticipated tasks. This strategy, along with associated contingency plans, will be a driver of EVA system requirements. Therefore, a medical contingency EVA scenario was performed with the Haughton-Mars Project/NASA to develop belay and medical evacuation techniques for exploration and rescue respectively. Methods: A rescue system to allow two rescuer astronauts to evacuate one in incapacitated astronaut was evaluated. The systems main components were a hard-bottomed rescue litter, hand-operated winch, rope, ground picket anchors, and a rover-winch attachment adapter. Evaluation was performed on 15-25deg slopes of dirt with embedded rock. The winch was anchored either by adapter to the rover or by pickets hammered into the ground. The litter was pulled over the surface by rope attached to the winch. Results: The rescue system was utilized effectively to extract the injured astronaut up a slope and to a waiting rover for transport to a simulated habitat for advanced medical care, although several challenges to implementation were identified and overcome. Rotational stabilization of the winch was found to be important to get maximize mechanical advantage from the extraction system. Discussion: Further research and testing needs to be performed to be able to fully consider synergies with the other Exploration surface systems, in conducting contingency operations. Structural attachment points on the surface EVA suits may be critical to assist in incapacitated evacuation. Such attach points could be helpful in microgravity incapacitated crewmember transport as well. Wheeled utility carts or wheels that may be attachable to a litter may also aid in extraction and transport. Utilizing parts of the rover (e.g. seats) to deploy as a litter may be considered. Testing in simulated 1/6-g to determine feasibility of winch operation and anchor establishment will further reduce implementation uncertainties.

Description: The advanced resistive exercise device (ARED), now at the prototype stage of development, is a versatile machine that can be used to perform different customized exercises for which, heretofore, it has been necessary to use different machines. Conceived as a means of helping astronauts and others to maintain muscle and bone strength and endurance in low-gravity environments, the ARED could also prove advantageous in terrestrial settings (e.g., health clubs and military training facilities) in which many users are exercising simultaneously and there is heavy demand for use of exercise machines.

Description: Higher-level physical laws applicable to biological tissues are presented that will permit the modeling of metabolic activity at the cellular level, including variations in the mass of a tissue. Here the tissue is represented as a fluid/solid mixture, wherein molecular solutes transport within the fluid, and cells can migrate throughout the porous solid. Variations in mass can arise via exchanges in mass between the constituent phases within a control volume such that mass is conserved in the tissue overall. The governing balance laws for mass, momentum, energy, and entropy are a special case of those describing a chemically reacting mixture with diffusion. Thermodynamic constraints on the constitutive structure are addressed. Biophysics; Biomechanics; Brownian motion; Cell migration; Mixture theory; Thermodynamic laws; Tissue mechanics

Description: The US-based health care system of the International Space Station (ISS) contains several subsystems, the Health Maintenance System, Environmental Health System and the Countermeasure System. These systems are designed to provide primary, secondary and tertiary medical prevention strategies. The medical system deployed in Low Earth Orbit (LEO) for the ISS is designed to enable a "stabilize and transport" concept of operations. In this paradigm, an ill or injured crewmember would be rapidly evacuated to a definitive medical care facility (DMCF) on Earth, rather than being treated for a protracted period on orbit. The medical requirements of the short (7 day) and long duration (up to 6 months) exploration class missions to the Moon are similar to LEO class missions with the additional 4 to 5 days needed to transport an ill or injured crewmember to a DCMF on Earth. Mars exploration class missions are quite different in that they will significantly delay or prevent the return of an ill or injured crewmember to a DMCF. In addition the limited mass, power and volume afforded to medical care will prevent the mission designers from manifesting the entire capability of terrestrial care. NASA has identified five Levels of Care as part of its approach to medical support of future missions including the Constellation program. In order to implement an effective medical risk mitigation strategy for exploration class missions, modifications to the current suite of space medical systems may be needed, including new Crew Medical Officer training methods, treatment guidelines, diagnostic and therapeutic resources, and improved medical informatics.

Description: The purpose of this review paper is to discuss the research literature on the effects of blood glucose levels on executive and non-executive functions in humans. The review begins with a brief description of blood glucose, how it has been studied, previous syntheses of prior studies, and basic results regarding the role of blood glucose on cognitive functioning. The following sections describe work that investigated the effect of blood glucose on both non-executive and executive functions (e.g., sensory processing, psychomotor functioning, attention, vigilance, memory, language and communication, judgement and decision-making, and complex task performance). Within each section, summaries of the findings and challenges to the literature are included. Measurement conversions of blood glucose levels, blood glucose values, and associated symptoms are depicted. References to the types of tests used to investigate blood glucose and cognitive performance are provided. For more detailed descriptions of references within (and in addition to) this paper, an annotated bibliography is also provided. Several moderator variables including individual differences and contextual variables related to the effects of blood glucose levels on performance (e.g., age, gender, time of day, familiarity with the task and symptom awareness, expectancy effects, dose dependent effects, time dependent effects, task specific effects, rising and falling blood glucose levels, and speed and/or accuracy trade-offs) are addressed later in the paper. Some suggestions for future experimental methodologies are also made.

Description: This viewgraph presentation reviews the efforts of the International Multidisciplinary Artificial Gravity Project. Specifically it reviews the NASA Exploration Planning Status, NASA Exploration Roadmap, Status of Planning for the Moon, Mars Planning, Reference health maintenance scenario, and The Human Research Program.

Description: The ISS may have communication gaps of up to 45 minutes during each orbit and therefore it is imperative to have medical protocols, including an effective ACLS algorithm, that can be reliably autonomously executed during flight. The aim of this project was to compare the effectiveness of the current ACLS algorithm with an improved algorithm having a new navigation format.

Description: Loss of functional weight bearing, such as experienced during space flight or bed rest (BR), distorts intervertebral disc (IVD) and muscle morphology. IVDs are avascular structures consisting of cells that may derive their nutrition and waste removal from the load induced fluid flow into and out of the disc. A diurnal cycle is produced by forces related to weight bearing and muscular activity, and comprised of a supine and erect posture over a 24 hr period. A diurnal cycle will include a disc volume change of approx. 10-13%. However, in space there are little or no diurnal changes because of the microgravity, which removes the gravitational load and compressive forces to the back muscles. The BR model and the etiology of the disc swelling and muscle atrophy could provide insight into those subjects confined to bed for chronic disease/injury and aging. We hypothesize that extremely low-magnitude, high frequency mechanical vibrations will abate the disc degeneration and muscle loss associated with long-term BR.

Description: Space medicine is primarily preventative medicine Outcomes of space medicine pharmaceutical care are: a) Elimination or reduction of a patient's symptomatology; b) Arresting or slowing of long term effects from microgravity; and c) Preventing long term effects or symptomatology as a result of microgravity. Space medicine pharmaceutical care is about both the patient and the mission. Pharmaceutical care in the area of space medicine is evolving. A pharmacist serves a critical role in this care. Commercial space travel will require pharmacist involvement.

Description: This viewgraph poster presentation reviews the rationale for a call for a new program in residency for aerospace pharmacy. Aerospace medicine provides a unique twist on traditional medicine, and a specialty has evolved to meet the training for physicians, and it is becoming important to develop such a program for training in pharmacy designed for aerospace. The reasons for this specialist training are outlined and the challenges of developing a program are reviewed.

Description: This viewgraph presentation is a course that reviews the diagnostic imaging techniques available for medical support on the future moon missions. The educational objectives of the course are to: 1) Update the audience on the curreultrasound imaging in space flight; 2) Discuss the unique aspects of conducting ultrasound imaging on ISS, interplanetary transit, ultrasound imaging on ISS, interplanetary transit, and lunar surface operations; and 3) Review preliminary data obtained in simulations of medical imaging in lunar surface operations.

Description: Coupled concentric-eccentric resistive exercise maintains bone mineral density (BMD) during bed rest and aging. PURPOSE: We hypothesized that 8 wks of lower body resistive exercise training with higher ratios of eccentric to concentric loading would enhance hip and lumbar BMD. METHODS: Forty untrained male volunteers (34.9+/-7.0 yrs, 80.9+/-9.8 kg, 178.2+/-7.1 cm; mean+/-SD) were matched for leg press (LP) 1-Repetition Maximum (1-RM) strength and randomly assigned to one of 5 training groups. Concentric load (% 1-RM) was constant across groups, but each group trained with different levels of eccentric load (0, 33, 66, 100, or 138% of concentric) for all training sessions. Subjects performed a periodized supine LP and heel raise (HR) training program 3 d wk-1 for 8 wks using a modified Agaton Fitness System (Agaton Fitness AB, Boden, Sweden). Hip and lumbar BMD (g/sq cm) was measured in triplicate pre- and post-training using DXA (Hologic Discovery ). Pre- and post-training means were compared using the appropriate ANOVA and Tukey's post hoc tests. Within group pre- to post-training BMD was compared using paired t-tests with a Bonferroni adjustment. RESULTS: There was a main effect of training on L1, L2, L3, L4, total lumbar, and greater trochanter BMD, but there were no differences between groups. CONCLUSION: Eights wks of lower body resistive exercise increased greater trochanter and lumbar BMD. Inability to detect group differences may have been influenced by a potentially osteogenic vibration associated with device operation in the 0, 33, and 66% groups.

Description: The aim of this research was to investigate cardiac autonomic changes associated with acute exposures to airborne particulates. Methods: High fidelity 12-lead ECG (CardioSoft, Houston, TX) was acquired from 19 (10 male / 9 female) non-smoking volunteers (age 33.6 +/- 6.6 yrs) during 10 minutes pre-exposure, exposure and post-exposure to environmental tobacco smoke (ETS), cooking oil fumes, wood smoke and sham (water vapor). To control exposure levels, noise, subject activity, and temperature, all studies were conducted inside an environmental chamber. Results: The short-term fractal scaling exponent (Alpha-1) and the ratio of low frequency to high frequency Heart Rate Variability (HRV) powers (LF/HF, a purported sympathetic index) were both higher in males (p〈0.017 and p〈0.05, respectively) whereas approximate entropy (ApEn) and HF/(LF+HF) (a purported parasympathetic index) were both lower in males (p〈0.036, and p〈0.044, respectively). Compared to pre-exposure (p〈0.0002) and sham exposure (p〈0.047), male heart rates were elevated during early ETS post-exposure. Our data suggest that, in addition to tonic HRV gender differences, cardiac responses to some acute airborne particulates are gender related.

Description: This viewgraph presentation reviews some of the techniques used to analyze the damage done to chromosome from ion radiation. Fluorescence in situ hybridization (FISH), mFISH, mBAND, telomere and centromereprobes have been used to study chromosome aberrations induced in human cells exposed to low-and high-LET radiation in vitro. There is some comparison of the different results from the various techniques. The results of the study are summarized.

Description: This viewgraph document reviews the radiation environment that is a significant potential hazard to NASA's goals for space exploration, of living and working in space. NASA has initiated a Peer reviewed research program that is charged with arriving at an understanding of the space radiation problem. To this end NASA Space Radiation Laboratory (NSRL) was constructed to simulate the harsh cosmic and solar radiation found in space. Another piece of the work was to develop a risk modeling tool that integrates the results from research efforts into models of human risk to reduce uncertainties in predicting risk of carcinogenesis, central nervous system damage, degenerative tissue disease, and acute radiation effects acute radiation effects.

Description: The Prebreathe Reduction Program (PRP) used exercise during oxygen prebreathe to reduce necessary prebreathe time prior to depressurizing to work in a 4.3 psi suit during extravehicular activity (EVA). Initial testing produced a two-hour protocol incorporating ergometry exercise and a 30 min cycle of depress/repress to 10.2 psi where subjects breathed 26.5% oxygen/balance nitrogen (Phase II - 10 min at 75% peak oxygen consumption [VO2 peak] followed by 40 min intermittent light exercise [ILE] [approx. 5.8 mL-per kilogram- per minute], then 50 min of rest). The Phase II protocol (0/45 DCS) was approved for operations and has been used on 40 EVAs, providing significant time savings compared to the standard 4 h resting oxygen prebreathe. The Phase V effort focused on performing all light in-suit exercise. Two oxygen prebreathe protocols were tested sequentially: V-4) 160 min prebreathe with 150 min of continuous ILE. The entire protocol was completed at 14.7 psi. All exercise involved upper body effort. Exercise continued until decompression. V-5) 160 min prebreathe with 140 min of ILE - first 40 min at 14.7 psi, then 30 min at 10.2 psi (breathing 26.5% oxygen) after a 20 min depress, simulating a suit donning period. Subjects were then repressed to 14.7 psi and performed another 50 min of lower body ILE, followed by 50 min rest before decompression. The V-4 protocol was rejected with 3 DCS/6 person-exposures. Initial V-5 testing has produced 0 DCS/11 person-exposures (ongoing trials). The difference in DCS rate was significant (Fisher Exact p=0.029). The observations of DCS were significantly lower in early V-5 trials than in V-4 trials. Additional studies are required to evaluate the relative contribution of the variables in exercise distribution, the 10.2 psi depress/repress component, pre-decompression rest, or possible variation in total oxygen consumption.

Description: Introduction: The cohort of NASA flight surgeons (FS) is a very accomplished group with varied clinical backgrounds; however, the NASA Flight Surgeon Office has identified that the extremely demanding schedule of this cohort prevents many of these physicians from practicing clinical medicine on a regular basis. In an effort to improve clinical competency, the NASA FS Office has dedicated one day a week for the FS to receive clinical training. Each week, an FS is assigned to one of five clinical settings, one being medical patient simulation. The Medical Operations Support Team (MOST) was tasked to develop curricula using medical patient simulation that would meet the clinical and operational needs of the NASA FS Office. Methods: The MOST met with the Lead FS and Training Lead FS to identify those core competencies most important to the FS cohort. The MOST presented core competency standards from the American Colleges of Emergency Medicine and Internal Medicine as a basis for developing the training. Results: The MOST identified those clinical areas that could be best demonstrated and taught using medical patient simulation, in particular, using high fidelity human patient simulators. Curricula are currently being developed and additional classes will be implemented to instruct the FS cohort. The curricula will incorporate several environments for instruction, including lab-based and simulated microgravity-based environments. Discussion: The response from the NASA FS cohort to the initial introductory class has been positive. As a result of this effort, the MOST has identified three types of training to meet the clinical needs of the FS Office; clinical core competency training, individual clinical refresher training, and just-in-time training (specific for post-ISS Expedition landings). The MOST is continuing to work with the FS Office to augment the clinical training for the FS cohort, including the integration of Web-based learning.

Description: To limit the risk of fire and reduce denitrogenation time to prevent decompression sickness to support frequent extravehicular activities on the Moon, a hypobaric (PB = 414 mmHg) and mildly hypoxic (ppO2 = 132 mmHg, 32% O2 - 68% N2) living environment is considered for the Crew Exploration Vehicle (CEV) and Lunar Surface Access Module (LSAM). With acute change in ppO2 from 145-178 mmHg at standard vehicular operating pressure to less than 125 mmHg at desired lunar surface vehicular operating pressures, there is the possibility that some crewmembers may develop symptoms of Acute Mountain Sickness (AMS). The signs and symptoms of AMS (headache plus nausea, dizziness, fatigue, or sleeplessness), could impact crew health and performance on lunar surface missions. An exhaustive literature review on the topic of the physiological effects of reduced ppO2 and absolute pressure as may contribute to the development of altitude symptoms or AMS was performed. The results of the nine most rigorous studies were collated, analyzed and contents on AMS and hypoxia symptoms summarized. There is evidence for an absolute pressure effect per se on AMS, so the higher the altitude for a given hypoxic alveolar O2 partial pressure (PAO2), the greater the AMS response. About 25% of adults are likely to experience mild AMS near 2,000 m altitude following a rapid ascent from sea level while breathing air (6,500 feet, acute PAO2 = 75 mmHg). The operational experience with the Shuttle staged denitrogenation protocol at 528 mmHg (3,048 m) while breathing 26.5% O2 (acute PAO2 = 85 mmHg) in astronauts adapting to microgravity suggests a similar likely experience in the proposed CEV environment. We believe the risk of mild AMS is greater given a PAO2 of 77 mmHg at 4,876 m altitude while breathing 32% O2 than at 1,828 m altitude while breathing 21% O2. Only susceptible astronauts would develop mild and transient AMS with prolonged exposure to 414 mmHg (4,876 m) while breathing 32% O2 (acute PAO2 = 77 mmHg). So the following may be employed for operational risk reduction: 1) develop procedures to increase PB as needed in the CEV, and use a gradual or staged reduction in cabin pressure during lunar outbound; 2) train crews for symptoms of hypoxia, to allow early recognition and consider pre-adaptation of crews to a hypoxic environment prior to launch, 3) consider prophylactic acetazolamide for acute pressure changes and be prepared to treat any AMS associated symptoms early with both carbonic anhydrase inhibitors and supplemental oxygen.

Description: We report a new model which uses hypovolemia to force humans into a hemodynamic state that is similar to that after spaceflight. This model can be used to test candidate countermeasures for postflight orthostatic hypotension and to identify crewmembers who will be most susceptible to that symptom on landing day.

Description: The goal of this work is to review the principles, design, and function of the ISS multilateral medical authority and the medical support system of the ISS Program. Multilateral boards and panels provide operational framework, direct, and supervise the ISS joint medical operational activities. The Integrated Medical Group (IMG) provides front-line medical support of the crews. Results of ongoing activities are reviewed weekly by physician managers. A broader status review is conducted monthly to project the state of crew health and medical support for the following month. All boards, panels, and groups function effectively and without interruptions. Consensus prevails as the primary nature of decisions made by all ISS medical groups, including the ISS medical certification board. The sustained efforts of all partners have resulted in favorable medical outcomes of the initial fourteen long-duration expeditions. The medical support system appears to be mature and ready for further expansion of the roles of all Partners, and for the anticipated increase in the size of ISS crews.

Description: Toe trajectory during the swing phase of locomotion has been identified as a precise motor control task (Karst, et al., 1999). The standard method for tracking toe trajectory is to place a marker on the superior aspect of the distal end of the 2nd toe itself (Karst, et al., 1999; Winter, 1992). However, others have based their toe trajectory results either on a marker positioned on the lateral aspect of the 5th metatarsal head (Dingwell, et al., 1999; Osaki, et al., 2007), or on a virtual toe marker computed at the anterior tip of the second toe based on the positions of other real foot markers (Miller, et al., 2006). While these methods for tracking the toe may seem similar, their results may not be directly comparable. The purpose of this study was to compute toe trajectory parameters using a 5th metatarsal marker and a virtual toe marker, and compare their results with those of the standard toe marker.

Description: The ability to read head-fixed displays on various motion platforms requires the suppression of vestibulo-ocular reflexes. This study examined dynamic visual acuity while viewing a head-fixed display during different self and surround rotation conditions. Twelve healthy subjects were asked to report the orientation of Landolt C optotypes presented on a micro-display fixed to a rotating chair at 50 cm distance. Acuity thresholds were determined by the lowest size at which the subjects correctly identified 3 of 5 optotype orientations at peak velocity. Visual acuity was compared across four different conditions, each tested at 0.05 and 0.4 Hz (peak amplitude of 57 deg/s). The four conditions included: subject rotated in semi-darkness (i.e., limited to background illumination of the display), subject stationary while visual scene rotated, subject rotated around a stationary visual background, and both subject and visual scene rotated together. Visual acuity performance was greatest when the subject rotated around a stationary visual background; i.e., when both vestibular and visual inputs provided concordant information about the motion. Visual acuity performance was most reduced when the subject and visual scene rotated together; i.e., when the visual scene provided discordant information about the motion. Ranges of 4-5 logMAR step sizes across the conditions indicated the acuity task was sufficient to discriminate visual performance levels. The background visual scene can influence the ability to read head-fixed displays during passive motion disturbances. Dynamic visual acuity using head-fixed displays can provide an operationally relevant screening tool for visual performance during exposure to novel acceleration environments.

Description: Motion sickness in the general population is a significant problem driven by the increasingly more sophisticated modes of transportation, visual displays, and virtual reality environments. It is important to investigate non-pharmacological alternatives for the prevention of motion sickness for individuals who cannot tolerate the available anti-motion sickness drugs, or who are precluded from medication because of different operational environments. Based on the initial work of Melvill Jones, in which post hoc results indicated that motion sickness symptoms were prevented during visual reversal testing when stroboscopic vision was used to prevent retinal slip, we have evaluated stroboscopic vision as a method of preventing motion sickness in a number of different environments. Specifically, we have undertaken a five part study that was designed to investigate the effect of stroboscopic vision (either with a strobe light or LCD shutter glasses) on motion sickness while: (1) using visual field reversal, (2) reading while riding in a car (with or without external vision present), (3) making large pitch head movements during parabolic flight, (4) during exposure to rough seas in a small boat, and (5) seated and reading in the cabin area of a UH60 Black Hawk Helicopter during 20 min of provocative flight patterns.

Description: The possibility of a traumatic bone fracture in space is a concern due to the observed decrease in astronaut bone mineral density (BMD) during spaceflight and because of the physical demands of the mission. The Bone Fracture Risk Module (BFxRM) was developed to quantify the probability of fracture at the femoral neck and lumbar spine during space exploration missions. The BFxRM is scenario-based, providing predictions for specific activities or events during a particular space mission. The key elements of the BFxRM are the mission parameters, the biomechanical loading models, the bone loss and fracture models and the incidence rate of the activity or event. Uncertainties in the model parameters arise due to variations within the population and unknowns associated with the effects of the space environment. Consequently, parameter distributions were used in Monte Carlo simulations to obtain an estimate of fracture probability under real mission scenarios. The model predicts an increase in the probability of fracture as the mission length increases and fracture is more likely in the higher gravitational field of Mars than on the moon. The resulting probability predictions and sensitivity analyses of the BFxRM can be used as an engineering tool for mission operation and resource planning in order to mitigate the risk of bone fracture in space.

Description: A viewgraph describing the medical contingencies of the international partner flight surgeons and biomedical engineer flight controllers aboard the International Space Station is shown.

Description: Maintaining health and fitness in crewmembers during space missions is essential for preserving performance for mission-critical tasks. NASA's Exercise Countermeasures Project (ECP) provides space exploration exercise hardware and monitoring requirements that lead to devices that are reliable, meet medical, vehicle, and habitat constraints, and use minimal vehicle and crew resources. ECP will also develop and validate efficient exercise prescriptions that minimize daily time needed for completion of exercise yet maximize performance for mission activities. In meeting these mission goals, NASA Glenn Research Center (Cleveland, OH, USA), in collaboration with the Cleveland Clinic (Cleveland, Ohio, USA), has developed a suite of zero-gravity locomotion simulators and associated technologies to address the need for ground-based test analog capability for simulating in-flight (microgravity) and surface (partial-gravity) exercise to advance the health and safety of astronaut crews and the next generation of space explorers. Various research areas can be explored. These include improving crew comfort during exercise, and understanding joint kinematics and muscle activation pattern differences relative to external loading mechanisms. In addition, exercise protocol and hardware optimization can be investigated, along with characterizing system dynamic response and the physiological demand associated with advanced exercise device concepts and performance of critical mission tasks for Exploration class missions. Three zero-gravity locomotion simulators are currently in use and the research focus for each will be presented. All of the devices are based on a supine subject suspension system, which simulates a reduced gravity environment by completely or partially offloading the weight of the exercising test subject s body. A platform for mounting treadmill is positioned perpendicularly to the test subject. The Cleveland Clinic Zero-g Locomotion Simulator (ZLS) utilizes a pneumatic subject load device to apply a near constant gravity-replacement load to the test subject during exercise, and is currently used in conjunction with the General Clinical Research Center for evaluating exercise protocols using a bedrest analog. The enhanced ZLS (eZLS) at NASA Glenn Research Center features an offloaded treadmill that floats on a thin film of air and interfaces to a force reaction frame via variably-compliant isolators, or vibration isolation system. The isolators can be configured to simulate compliant interfaces to the vehicle, which affects mechanical loading to crewmembers during exercise, and has been used to validate system dynamic models for new countermeasures equipment designs, such as the second International Space Station treadmill slated for use in 2010. In the eZLS, the test subject and exercise device can be pitched at the appropriate angle for partial gravity simulations, such as lunar gravity (1/6th earth gravity). On both the eZLS and the NASA-Johnson Space Center standalone ZLS installed at the University of Texas Medical Branch in Galveston, Texas, USA, the subject's body weight relative to the treadmill is controlled via a linear motor subject load device (LM-SLD). The LM-SLD employs a force-feedback closed-loop control system to provide a relatively constant force to the test subject during locomotion, and is set and verified for subject safety prior to each session. Locomotion data were collected during parabolic flight and on the eZLS. The purpose was to determine the similarities and differences between locomotion in actual and simulated microgravity. Subjects attained greater amounts of hip flexion during walking and running during parabolic flight. During running, subjects had greater hip range of motion. Trunk motion was significantly less on the eZLS than during parabolic flight. Peak impact forces, loading rate, and impulse were greater on the eZLS than during parabolic while walking with a low external load (EL) and rning with a high EL. Activation timing differences existed between locations in all muscles except for the rectus femoris. The tibialis anterior and gluteus maximus were active for longer durations on the eZLS than in parabolic flight during walking. Ground reaction forces were greater with the LM-SLD than with bungees during eZLS locomotion. While the eZLS serves as a ground-based analog, researchers should be aware that subtle, but measurable, differences in kinematics and leg musculature activities exist between the environments. Aside from space applications, zero-gravity locomotion simulators may help medical researchers in the future with development of rehabilitative or therapeutic protocols for injured or ill patients. Zero-gravity locomotion simulators may be used as a ground-based test bed to support future missions for space exploration, and eventually may be used to simulate planetary locomotion in partial gravity environments, including the Moon and Mars. Figure: Zero-gravity Locomotion Simulator at the Cleveland Clinic, Cleveland, Ohio, USA

Description: The Space Medicine Operations Team (SMOT) was created to integrate International Space Station (ISS) Medical Operations, promote awareness of all Partners, provide emergency response capability and management, provide operational input from all Partners for medically relevant concerns, and provide a source of medical input to ISS Mission Management. The viewgraph presentation provides an overview of educational objectives, purpose, operations, products, statistics, and its use in off-nominal situations.

Description: Background. VZV DNA is present in saliva of healthy astronauts and patients with Ramsay Hunt syndrome (geniculate zoster). We hypothesized that a prospective analysis of patients with zoster would detect VZV in saliva independent of zoster location. Methods. We treated 54 patients with valacyclovir. On the first treatment day, 7- and 14-days later, pain was scored and saliva examined for VZV DNA. Saliva from six subjects with chronic pain and 14 healthy subjects was similarly studied. Results. Follow-up data was available for 50/54 patients. Pain decreased in 43/50 (86 percent), disappeared in 37 (74 percent), recurred after disappearing in three (6 percent) and increased in four (8 percent). VZV DNA was found in every patient the day treatment was started, decreased in 47/50 (94 percent), transiently increased in three (6 percent) before decreasing, increased in two (4 percent) and disappeared in 41 (82 percent). There was a positive correlation between the presence of VZV DNA and pain, as well as between the VZV DNA copy number and pain (P〈0.0005). Saliva of two patients was cultured, and infectious VZV was isolated from one. VZV DNA was present in one patient before rash and in four patients after pain resolved, and not in any control subjects. Conclusion. VZV DNA is present in saliva of zoster patients.

Description: The thesis of this session of the ECP Bone workshop is that computer modeling is required in order to evaluate factor of risk for fracture when considering the uniquely localized bone loss conditions experienced by Astronauts. This session provides an opportunity to introduce the Integrated Medical Model Bone Fracture Risk (IMM-BFxRM) simulation approach and how this and other models improve understanding of the effects of exercise countermeasures. This workshop session also provides an opportunity for the panel to provide recommendations on this and other "complex modeling" approaches, as well as, the importance of funding the IMM-BFxRM and companion efforts by external scientists (Lang and Keyak).

Description: Airway management techniques are necessary to establish and maintain a patent airway while treating a patient undergoing respiratory distress. There are situations where such settings are suboptimal, thus causing the caregiver to adapt to these suboptimal conditions. Such occurrences are no exception aboard the International Space Station (ISS). As a result, the NASA flight surgeon (FS) and NASA astronaut cohorts must be ready to adapt their optimal airway management techniques for suboptimal situations. Based on previous work conducted by the Medical Operation Support Team (MOST) and other investigators, the MOST had members of both the FS and astronaut cohorts evaluate two oral airway insertion techniques for the Intubating Laryngeal Mask Airway (ILMA) to determine whether either technique is sufficient to perform in suboptimal conditions within a microgravity environment. Methods All experiments were conducted in a simulated microgravity environment provided by parabolic flight aboard DC-9 aircraft. Each participant acted as a caregiver and was directed to attempt both suboptimal ILMA insertion techniques following a preflight instruction session on the day of the flight and a demonstration of the technique by an anesthesiologist physician in the simulated microgravity environment aboard the aircraft. Results Fourteen participants conducted 46 trials of the suboptimal ILMA insertion techniques. Overall, 43 of 46 trials (94%) conducted were properly performed based on criteria developed by the MOST and other investigators. Discussion The study demonstrated the use of airway management techniques in suboptimal conditions relating to space flight. Use of these techniques will provide a crew with options for using the ILMA to manage airway issues aboard the ISS. Although it is understood that the optimal method for patient care during space flight is to have both patient and caregiver restrained, these techniques provide a needed backup should conditions not present themselves in an ideal manner.

Description: This viewgraph document is comprised of two presentations about Bone Research at NASA. The first document has slides that show the percent of bone loss from specific bones as demonstrated from research of the Mir cosmonauts, and the required preflight and postflight BMD measurements for long duration flights. The second presentation entitled "Recovery of Spaceflight-induced Bone Loss: Bone Mineral Density after Long-duration Missions as Fitted with an Exponential Function" reviews the recovery of Bone Mineral Density (BMD) after long duration missions. Between 1990 and 2004, 56 missions were flown with 45 crewmembers for an average of 181 days +/- 47 days. For each of these flights the change in BMD was calculated after the flight. The BMD changes were plotted against the number of days for bone recovery after the landing. The plots for the bones that were measured are shown.

Description: This viewgraph presentation reviews NASA's role in medical translational research, and the importance in research for space exploration. The application of medical research for space exploration translates to health care in space medicine, and on earth.

Description: Clinical and translational research (CTR) is an essential part of a sustainable global health system. Informatics is now recognized as an important en-abler of CTR and informaticians are increasingly called upon to help CTR efforts. The US National Institutes of Health mandated biomedical informatics activity as part of its new national CTR grant initiative, the Clinical and Translational Science Award (CTSA). Traditionally, translational re-search was defined as the translation of laboratory discoveries to patient care (bench to bedside). We argue, however, that there are many other kinds of translational research. Indeed, translational re-search requires the translation of knowledge dis-covered in one domain to another domain and is therefore an information-based activity. In this panel, we will expand upon this view of translational research and present three different examples of translation to illustrate the point: 1) bench to bedside, 2) Earth to space and 3) academia to community. We will conclude with a discussion of our local translational research efforts that draw on each of the three examples.

Description: This viewgraph presentation reviews the use of telemedicine in a simulated microgravity environment using a patient simulator. For decades, telemedicine techniques have been used in terrestrial environments by many cohorts with varied clinical experience. The success of these techniques has been recently expanded to include microgravity environments aboard the International Space Station (ISS). In order to investigate how an astronaut crew medical officer will execute medical tasks in a microgravity environment, while being remotely guided by a flight surgeon, the Medical Operation Support Team (MOST) used the simulated microgravity environment provided aboard DC-9 aircraft teams of crew medical officers, and remote flight surgeons performed several tasks on a patient simulator.

Description: The moon's surface is covered with a thin layer of fine, charged, reactive dust capable of layer of fine, charged, reactive dust capable of capable of entering habitats and vehicle compartments, where it can result in crewmember health problems. NASA formed the Lunar Airborne Dust Toxicity Advisory Group (LADTAG) to study the effects of exposure to Lunar Dust on human health. To date, no scientifically defensible toxicological studies have been performed on lunar dusts, specifically the determination of exposure limits and their affect on human health. The multi-center LADTAG (Lunar Airborne Dust Toxicology center LADTAG (Lunar Airborne Dust Toxicology Advisory Group) was formed in response to the Office of the Chief Health and Medical Office s (OCHMO) request to develop recommendations for defining risk (OCHMO) request to develop recommendations for defining risk defining risk criteria for human lunar dust exposure.

Description: This paper describes the intravenous (IV) fluids requirements being developed for medical care during NASA s future exploration class missions. Previous research on IV solution generation and mixing in space is summarized. The current exploration baseline mission profiles are introduced, potential medical conditions described and evaluated for fluidic needs, and operational issues assessed. We briefly introduce potential methods for generating IV fluids in microgravity. Conclusions on the recommended fluid volume requirements are presented.

Description: This viewgraph presentation describes the challenges that space exploration faces in terms of medicine, research and ethics. The topics include: 1) Effects of Microgravity on Human Physiology; 2) Radiation; 3) Bone; 4) Behavior and Performance; 5) Muscle; 6) Cardiovascular; 7) Neurovestibular; 8) Food and Nutrition; 9) Immunology and Hematology; 10) Environment; 11) Exploration; 12) Building Block Approach; 13) Exploration Issues; 14) Life Sciences Contributions; 15) Health Care; and 17) Habitability.

Description: This viewgraph document reviews the sources of Nano particles in the environment, the structure and properties of Carbon Nanotubes (CNTs), the physical characteristics of CNT materials, pulmonary and other health concerns of exposure to CNTs. The toxicity of CNT in rodents is summarized and some natural, and man-made sources of CNTs are shown. CNTs are electrically and thermally conductive, fibrous, biopersistent and very complicated in structures. The factors affecting toxicity of CNTs are more than size and surface area.

Description: Do gaseous micronuclei trigger the formation of bubbles in decompression sickness (DCS)? Most previous instructions for DCS prevention have been oriented toward supersaturated gas in tissue. We are developing a mathematical model that is oriented toward the expected behavior of micronuclei. The issue is simplified in altitude decompressions because the aviator or astronaut is exposed only to decompression, whereas in diving there is a compression before the decompression. The model deals with four variables: duration of breathing of 100% oxygen before going to altitude (O2 prebreathing), altitude of the exposure, exposure duration, and rate of ascent. Assumptions: a) there is a population of micronuclei of various sizes having a range of characteristics, b) micronuclei are stable until they grow to a certain critical nucleation radius, c) it takes time for gas to diffuse in or out of micronuclei, and d) all other variables being equal, growth of micronuclei upon decompression is more rapid at high altitude because of the rarified gas in the micronuclei. To estimate parameters, we use a dataset of 4,756 men in altitude chambers exposed to various combinations of the model s variables. The model predicts occurrence of DCS symptoms quite well. It is notable that both the altitude chamber data and the model show little effect of O2 prebreathing until it lasts more than 60 minutes; this is in contrast to a conventional idea that the benefit of prebreathing is directly due to exponential washout of tissue nitrogen. The delay in response to O2 prebreathing can be interpreted as time required for outward diffusion of nitrogen; when the micronuclei become small enough, they are disabled, either by crushing or because they cannot expand to a critical nucleation size when the subject ascends to altitude.

Description: During locomotion, humans adapt their motor patterns to maintain coordination despite changing conditions (Reisman et al., 2005). Bernstein (1967) proposed that in addition to the present state of a given joint, other factors, including limb inertia and velocity, must be taken into account to allow proper motion to occur. During locomotion with added mass counterbalanced using vertical suspension to maintain body weight, vertical ground reaction forces (GRF's) increase during walking but decrease during running, suggesting that adaptation may be velocity-specific (De Witt et al., 2006). It is not known, however, how lower extremity joint torques adapt to changes in inertial forces. The purpose of this investigation was to examine the effects of increasing body mass while maintaining body weight upon lower-limb joint torque during walking and running. We hypothesized that adaptations in joint torque patterns would occur with the addition of body mass.

Description: A viewgraph presentation on biomedical data from International Space Station (ISS) Expeditions 1-12 is shown. The topics include: 1) ISS Expeditions 1-12; 2) Biomedical Data; 3) Physiological Assessments; 4) Bone Mineral Density; 5) Bone Mineral Density Recovery; 6) Orthostatic Tolerance; 7) Postural Stability Set of Sensory Organ Test 6; 8) Performance Assessment; 9) Aerobic Capacity of the Astronaut Corps; 10) Pre-flight Aerobic Fitness of ISS Astronauts; 11) In-flight and Post-flight Aerobic Capacity of the Astronaut Corps; and 12) ISS Functional Fitness Expeditions 1-12.

Description: The goal of this study is to determine the role that moisture plays in the injury to the fingers and fingernails during EVA training operations in the Neutral Buoyancy Laboratory. Current Extravehicular Mobility Unit (EMU, with a PLSS) as configured in the NBL was used for all testing and a vent tube was extended down a single arm of the crewmember during the test; vent tube was moved between left and right arm to serve as experimental condition being investigated and the other arm served as control condition.