ALBERT

Description: Cells respond to a wide range of mechanical stimuli such as fluid shear and strain, although the contribution of gravity to cell structure and function is not understood. We hypothesized that bone-forming osteoblasts are sensitive to increased mechanical loading by hypergravity. A centrifuge suitable for cell culture was developed and validated, and then primary cultures of fetal rat calvarial osteoblasts at various stages of differentiation were mechanically loaded using hypergravity. We measured microtubule network morphology as well as release of the paracrine factor prostaglandin E2 (PGE2). In immature osteoblasts, a stimulus of 10x gravity (10 g) for 3 h increased PGE2 2.5-fold and decreased microtubule network height 1.12-fold without affecting cell viability. Hypergravity (3 h) caused dose-dependent (5-50 g) increases in PGE2 (5.3-fold at 50 g) and decreases (1.26-fold at 50 g) in microtubule network height. PGE2 release depended on duration but not orientation of the hypergravity load. As osteoblasts differentiated, sensitivity to hypergravity declined. We conclude that primary osteoblasts demonstrate dose- and duration-dependent sensitivity to gravitational loading, which appears to be blunted in mature osteoblasts.

Description: The purpose of this study was to compare the bone changes induced by unloading in rats fed different diets, because space flight studies use a semipurified diet, whereas space flight simulation studies typically use nonpurified diets. Female Sprague-Dawley rats were fed a purified American Institute of Nutrition (AIN) 93G diet or a standard nonpurified diet and kept ambulatory or subjected to unloading by hindlimb suspension (HLS) for 38 days. Bone mineral content (BMC), mechanical strength, and factors related to the diet that affect bone (i.e., urinary calcium excretion, estradiol, and corticosterone) were measured. Average food intakes (grams per day) differed for diets, but caloric intake (kilocalories per day) and the final body masses of treatment groups were similar. The HLS-induced decrease in femoral BMC was not statistically different for rats fed a nonpurified diet (-8.6%) compared with a purified AIN-93G diet (-11.4%). The HLS-induced decrease in femoral mechanical strength was not statistically different for rats fed a nonpurified diet (-24%) compared with a purified AIN-93G diet (-31%). However, bone lengths were decreased (P 〈 0.05) in rats fed a nonpurified diet compared with a purified diet. Plasma estradiol levels were lower (P 〈 0.05) in the HLS/AIN-93G group but similar in the HLS and ambulatory rats fed a nonpurified diet. Plasma estradiol was related to femoral BMC (r = 0.85, P 〈 0.01). Urinary calcium excretion was higher (P 〈 0.05) in rats fed a nonpurified diet than those fed a purified AIN-93G diet, which is consistent with the higher level of calcium in the nonpurified diet. Urinary corticosterone levels were higher (P 〈 0.05) in rats fed a nonpurified diet than rats fed the AIN-93G diet. Although the osteopenia induced by unloading was similar in both diet groups, there were differences in longitudinal bone growth, calcium excretion, plasma estradiol levels, and urinary corticosterone levels. Results indicate that the type of standard diet used is an important factor to consider when measuring bone end points.

Description: Intact and operated newts Pleumdeles waltl flown on Foton-M2 for 16 days were used to study the effects of spaceflight as well as tail amputation and lensectomy on their hemopoiesis. The flight did not produce noticeable changes in the peripheral blood of nonoperated newts. However, in operated animals, the number of lymphocytes increased whereas that of neutrophils decreased. There were no morphological differences in hemopoietic organs (liver and spleen) between flown non-operated and operated animals or their controls. However, in both non-operated and operated newts the liver weight and the number of hemopoietic cells in it increased. In contrast to nonoperated newts, space-flown mammals typically showed significant changes in blood cell counts. Experiments with BrdU incorporation revealed labeled cells in the hemopoietic area of the liver as well as in blood and spleen. This observation gives evidence that the BrdU label can be used to study proliferation of hemopoietic cells.

Description: There are grounds to believe that space flown experiments on thick-toed geckos may help solve the problem of floatation of vertebrates in microgravity. Geckos of this species carry on the lower surface of their toes numerous setae, which allow them to remain attached to any surfaces regardless of the gravitational effects. Experiments were performed on 5 animals in each of the following groups: flight, basal, synchronous and laboratory controls. 32 hours after a 16- day flight the animals were euthanazed and examined using traditional histology and X-ray microtomography. Body mass losses were 10% in the flight animals, 7.4% in the synchronous controls, and 12.3% in the laboratory controls. Since the flight and synchronous animals were kept at 15-19 C, whereas the laboratory controls - at 26-28 C, it can be inferred that environmental temperatures impacted animal metabolism no less than flight induced stress. Blood tests of the flown animals showed a 12% decrease of erythrocytes and a 40% decrease of dark-nuclear granulocytes, with the number of light-nuclear granulocytes remaining unchanged. In the small intestine the number of goblet cells increased allowing them to occupy a large portion of the cyptal surface. Enhanced secretion was accompanied by the appearance of dead intestinal cells in the lumen. Clusters of degraded hepatocytes were found at the liver edges of flight animals. Signs of liver involution were similar to the changes produced by alcohol consumption but did not spread to its central part. In the heart, insignificant hypertrophy and excessive blood supply that still remained within the physiological norm were detected. No significant changes were found in the pancreas, lungs, nervous systems or the snouts of the flown animals, but the volume of their gallbladders was greater than in controls. The epithelium of toe pads of the flight animals became thinner. Histological examination of the humerus did not demonstrate significant mineral losses. However, X-ray microtomography showed changes in the trabecular structure in the subepyphyseal zone of bones in flight animals compared to the controls. In summary, all the changes detected in the flight animals were adaptive. Therefore, geckos of this species can be used as an animal model for morphological studies in longer-duration space flights.

Description: High-protein and acidogenic diets induce hypercalciuria. Foods or supplements with excess sulfur-containing amino acids increase endogenous sulfuric acid production and therefore have the potential to increase calcium excretion and alter bone metabolism. In this study, effects of an amino acid/carbohydrate supplement on bone resorption were examined during bed rest. Thirteen subjects were divided at random into two groups: a control group (Con, n = 6) and an amino acid-supplemented group (AA, n = 7) who consumed an extra 49.5 g essential amino acids and 90 g carbohydrate per day for 28 days. Urine was collected for n-telopeptide (NTX), deoxypyridinoline (DPD), calcium, and pH determinations. Bone mineral content was determined and potential renal acid load was calculated. Bone-specific alkaline phosphatase was measured in serum samples collected on day 1 (immediately before bed rest) and on day 28. Potential renal acid load was higher in the AA group than in the Con group during bed rest (P 〈 0.05). For all subjects, during bed rest urinary NTX and DPD concentrations were greater than pre-bed rest levels (P 〈 0.05). Urinary NTX and DPD tended to be higher in the AA group (P = 0.073 and P = 0.056, respectively). During bed rest, urinary calcium was greater than baseline levels (P 〈 0.05) in the AA group but not the Con group. Total bone mineral content was lower after bed rest than before bed rest in the AA group but not the Con group (P 〈 0.05). During bed rest, urinary pH decreased (P 〈 0.05), and it was lower in the AA group than the Con group. These data suggest that bone resorption increased, without changes in bone formation, in the AA group.

Description: Spaceflight and prolonged bed rest (BR) alter plasma hormone levels inconsistently. This may be due, in part, to prescription of heavy exercise as a countermeasure for ameliorating the adverse effects of disuse. The initial project was to assess exercise programs to maintain aerobic performance and leg strength during BR. The present study evaluates the effect of BR and the performance of the prescribed exercise countermeasures on plasma steroid levels. In a 30-day BR study of male subjects, the efficacy of isotonic (ITE, n = 7) or isokinetic exercise (IKE, n = 7) training was evaluated in contrast to no exercise (n = 5). These exercise countermeasures protected aerobic performance and leg strength successfully. BR alone (no-exercise group) did not change steroidogenesis, as assessed by the plasma concentrations of cortisol, progesterone, aldosterone, and free (FT) and total testosterone (TT). In the exercise groups, both FT and TT were decreased (P 〈 0.05): FT during IKE from 24 +/- 1.7 to 18 +/- 2.0 pg/ml and during ITE from 21 +/- 1.5 to 18 +/- 1 pg/ml, and TT during IKE from 748 +/- 68 to 534 +/- 46 ng/dl and during ITE from 565 +/- 36 to 496 +/- 38 ng/dl. The effect of intensive exercise countermeasures on plasma testosterone was not associated with indexes of overtraining. The reduction in plasma testosterone associated with both the IKE and ITE countermeasures during BR supports our hypothesis that intensive exercise countermeasures may, in part, contribute to changes in plasma steroid concentrations during spaceflight.

Description: The Behavioral Health and Performance Section (BHP) at NASA Johnson Space Center provides direct and indirect psychological services to the International Space Station (ISS) astronauts and their families. Beginning with the NASA-Mir Program, services available to the crews and families have gradually expanded as experience is gained in long-duration flight. Enhancements to the overall BHP program have been shaped by crewmembers' personal preferences, family requests, specific events during the missions, programmatic requirements, and other lessons learned. The BHP program focuses its work on four areas: operational psychology, behavioral medicine, human-to-system interface, and sleep and circadian. Within these areas of focus are psychological and psychiatric screening for astronaut selection as well as many resources that are available to the crewmembers, families, and other groups such as crew surgeon and various levels of management within NASA. Services include: preflight, in flight, and postflight preparation; training and support; resources from a Family Support Office; in-flight monitoring; clinical care for astronauts and their families; and expertise in the workload and work/rest scheduling of crews on the ISS. Each of the four operational areas is summarized, as are future directions for the BHP program.

Description: Microgravity and its environment have adverse effects on the immune system. Abnormal immune responses observed in microgravity may pose serious consequences, especially for the recent directions of NASA for long-term space missions to Moon, Mars and deep Space exploration. The study of space flight immunology is limited due to relative inaccessibility, difficulty of performing experiments in space, and inadequate provisions in this area in the United States and Russian space programs (Taylor 1993). Microgravity and stress experienced during space flights results in immune system aberration (Taylor 1993). In ground-based mouse models for some of the microgravity effects on the human body, hindlimb unloading (HU) has been reported to cause abnormal cell proliferation and cytokine production (Armstrong et al., 1993, Chapes et al. 1993). In this report, we document that a nutritional nucleotide supplementation as studied in ground-based microgravity analogs, has potential to serve as a countermeasure for the immune dysfunction observed in space travel.

Description: No abstract available

Description: Maintaining optimal alertness and neurobehavioral functioning during space operations is critical to enable the National Aeronautics and Space Administration's (NASA's) vision "to extend humanity's reach to the Moon, Mars and beyond" to become a reality. Field data have demonstrated that sleep times and performance of crewmembers can be compromised by extended duty days, irregular work schedules, high workload, and varying environmental factors. This paper documents evidence of significant sleep loss and disruption of circadian rhythms in astronauts and associated performance decrements during several space missions, which demonstrates the need to develop effective countermeasures. Both sleep and circadian disruptions have been identified in the Behavioral Health and Performance (BH&P) area and the Advanced Human Support Technology (AHST) area of NASA's Bioastronautics Critical Path Roadmap. Such disruptions could have serious consequences on the effectiveness, health, and safety of astronaut crews, thus reducing the safety margin and increasing the chances of an accident or incident. These decrements oftentimes can be difficult to detect and counter effectively in restrictive operational environments. NASA is focusing research on the development of optimal sleep/wake schedules and countermeasure timing and application to help mitigate the cumulative effects of sleep and circadian disruption and enhance operational performance. Investing research in humans is one of NASA's building blocks that will allow for both short- and long-duration space missions and help NASA in developing approaches to manage and overcome the human limitations of space travel. In addition to reviewing the current state of knowledge concerning sleep and circadian disruptions during space operations, this paper provides an overview of NASA's broad research goals. Also, NASA-funded research, designed to evaluate the relationships between sleep quality, circadian rhythm stability, and performance proficiency in both ground-based simulations and space mission studies, as described in the 2003 NASA Task Book, will be reviewed.

Description: INTRODUCTION: The performance of complex tasks on the International Space Station (ISS) requires significant preflight crew training commitments and frequent skill and knowledge refreshment. This report documents a recently developed "just-in-time" training methodology, which integrates preflight hardware familiarization and procedure training with an on-orbit CD-ROM-based skill enhancement. This "just-in-time" concept was used to support real-time remote expert guidance to complete ultrasound examinations using the ISS Human Research Facility (HRF). METHODS: An American and Russian ISS crewmember received 2 h of "hands on" ultrasound training 8 mo prior to the on-orbit ultrasound exam. A CD-ROM-based Onboard Proficiency Enhancement (OPE) interactive multimedia program consisting of memory enhancing tutorials, and skill testing exercises, was completed by the crewmember 6 d prior to the on-orbit ultrasound exam. The crewmember was then remotely guided through a thoracic, vascular, and echocardiographic examination by ultrasound imaging experts. RESULTS: Results of the CD-ROM-based OPE session were used to modify the instructions during a complete 35-min real-time thoracic, cardiac, and carotid/jugular ultrasound study. Following commands from the ground-based expert, the crewmember acquired all target views and images without difficulty. The anatomical content and fidelity of ultrasound video were adequate for clinical decision making. CONCLUSIONS: Complex ultrasound experiments with expert guidance were performed with high accuracy following limited preflight training and multimedia based in-flight review, despite a 2-s communication latency. In-flight application of multimedia proficiency enhancement software, coupled with real-time remote expert guidance, facilitates the successful performance of ultrasound examinations on orbit and may have additional terrestrial and space applications.

Description: NASA's participation in nearly 10 yr of long-duration mission (LDM) training and flight confirms that these missions remain a difficult challenge for astronauts and their medical care providers. The role of the astronaut's crew surgeon is to maximize the astronaut's health throughout all phases of the LDM: preflight, in flight, and postflight. In support of the crew surgeon, the NASA-Johnson Space Center Behavioral Health and Performance Group (JSC-BHPG) has focused on four key factors that can reduce the astronaut's behavioral health and performance. These factors are defined as: sleep and circadian factors; behavioral health factors; psychological adaptation factors; and human-to-system interface (the interface between the astronaut and the mission workplace) factors. Both the crew surgeon and the JSC-BHPG must earn the crewmember's trust preflight to encourage problem identification and problem solving in these four areas. Once on orbit, the crew medical officer becomes a valuable extension of the crew surgeon and BHPG on the ground due to the crew medical officer's constant interaction with crewmembers and preflight training in these four factors. However, the crew surgeon, BHPG, and the crew medical officer need tools that will help predict, prevent, monitor, and respond to developing problems. Objective data become essential when difficult mission termination decisions must be made. The need for behavioral health and performance tool development creates an environment rich for collaboration between operational healthcare providers and researchers. These tools are also a necessary step to safely complete future, more autonomous exploration-class space missions.

Description: In response to hypergravity, it appears that the larger the animal, the greater the response, if present. Therefore, the response of a rat exceeds that of a mouse in the same hypergravity environment. When investigated in the microgravity environment of space flight, this appears to hold true. The lack of definitive data obtained in space for either species makes the extrapolation of the continuum to levels below Earth-gravity problematic. However, in systems where responses are detected for both space flight and acceleration by centrifugation, a gravitational continuum is present supporting the "principle of continuity". For those and similar systems, it appears that the use of hypergravity could be used to predict responses to space flight.

Description: The deleterious effects of skeletal unloading on bone mass and strength may, in part, result from increased production of oxygen-derived free radicals and proinflammatory cytokines. This study was designed to evaluate the ability of vitamin E (alpha-tocopherol), a free-radical scavenger with antiinflammatory properties, to protect against bone loss caused by skeletal unloading in mature male Sprague-Dawley rats. A 2 x 3 factorial design was used with either hindlimb unloading (HU) or normal loading (ambulatory; AMB), and low-dose (LD; 15 IU/kg diet), adequate-dose (AD; 75 IU/kg diet), or high-dose (HD; 500 IU/kg diet) vitamin E (DL-alpha-tocopherol acetate). To optimize the effects of vitamin E on bone, dietary treatments were initiated 9 weeks prior to unloading and continued during the 4-week unloading period, at which time animals were euthanized and blood and tissue samples were collected. Serum vitamin E was dose-dependently increased, confirming the vitamin E status of animals. The HD treatment improved oxidation parameters, as indicated by elevated serum ferric-reducing ability and a trend toward reducing tissue lipid peroxidation. Histomorphometric analysis of the distal femur revealed significant reductions in trabecular thickness (TbTh), double-labeled surface (dLS/BS), and rate of bone formation to bone volume (BFR/BV) due by HU. AMB animals on the HD diet and HU animals on the LD diet had reduced bone surface normalized to tissue volume (BS/TV) and trabecular number (TbN); however, the HD vitamin E protected against these changes in the HU animals. Our findings suggest that vitamin E supplementation provides modest bone protective effects during skeletal unloading.

Description: No abstract available

Description: No abstract available

Description: A novel, unobtrusive and wearable, multiparameter ambulatory physiologic monitoring system for space and terrestrial applications, termed LifeGuard, is presented. The core element is a wearable monitor, the crew physiologic observation device (CPOD), that provides the capability to continuously record two standard electrocardiogram leads, respiration rate via impedance plethysmography, heart rate, hemoglobin oxygen saturation, ambient or body temperature, three axes of acceleration, and blood pressure. These parameters can be digitally recorded with high fidelity over a 9-h period with precise time stamps and user-defined event markers. Data can be continuously streamed to a base station using a built-in Bluetooth RF link or stored in 32 MB of on-board flash memory and downloaded to a personal computer using a serial port. The device is powered by two AAA batteries. The design, laboratory, and field testing of the wearable monitors are described.

Description: There is little evidence obtained from space flight to support the notion that occurrence of cardiac dysrhythmias, impaired cardiac and vascular function, and manifestation of asymptomatic cardiovascular disease represent serious risks during space flight. Therefore, the development of orthostatic hypotension and instability immediately after return from spaceflight probably reflect the most significant operational risks associated with the cardiovascular system of astronauts. Significant reductions in stroke volume and lower reserve for increasing peripheral vascular resistance contribute to ineffective maintenance of systemic arterial blood pressure during standing after spaceflight despite compensatory elevations in heart rate. The primary mechanism underlying reduced stroke volume appears to be a reduction in preload associated with less circulating blood volume while inadequate peripheral vasoconstriction may be caused partly by hyporeactivity of receptors that control arterial smooth muscle function. A focus for development of future countermeasures for hemodynamic responses to central hypovolemia includes the potential application of pharmacological agents that specifically target and restore blood volume (e.g., fludrocortisone, electrolyte-containing beverages) and reserve for vasoconstriction (e.g., midodrine, vasopressin). Based on systematic evaluations, acute physical exercise designed to elicit maximal effort or inspiratory resistance have shown promise as successful countermeasures that provide protection against development of orthostatic hypotension and intolerance without potential risks and side effects associated with specific pharmacological interventions.

Description: No abstract available

Description: The hindlimb unloading rodent model is used extensively to study the response of many physiological systems to certain aspects of space flight, as well as to disuse and recovery from disuse for Earth benefits. This chapter describes the evolution of hindlimb unloading, and is divided into three sections. The first section examines the characteristics of 1064 articles using or reviewing the hindlimb unloading model, published between 1976 and April 1, 2004. The characteristics include number of publications, journals, countries, major physiological systems, method modifications, species, gender, genetic strains and ages of rodents, experiment duration, and countermeasures. The second section provides a comparison of results between space flown and hindlimb unloading animals from the 14-day Cosmos 2044 mission. The final section describes modifications to hindlimb unloading required by different experimental paradigms and a method to protect the tail harness for long duration studies. Hindlimb unloading in rodents has enabled improved understanding of the responses of the musculoskeletal, cardiovascular, immune, renal, neural, metabolic, and reproductive systems to unloading and/or to reloading on Earth with implications for both long-duration human space flight and disuse on Earth.

Description: No abstract available

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

Description: Medullary Sponge Kidney (MSK) is a benign disorder associated with renal stones in 60% of patients. Patients frequently have episodic painless hematuria but are otherwise asymptomatic unless renal calculi or infections complicate the disease. Nephrolithiasis is a relative, but frequently enforced, contraindication to space or other high performance flight. Two case reports of asymptomatic NASA flight crew with MSK and three cases of military aviators diagnosed with MSK are reviewed, all cases resulted in waiver and return to flight status after treatment and a vigorous follow up and prophylaxis protocol. MSK in aviation and space flight necessitates a highly case-by-case dependent evaluation and treatment process to rule out other potential confounding factors that might also contribute to stone formation and in order to re-qualify the aviator for flight duties.

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: 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 a necessity in normal gravity on Earth, in microgravity, and when applying artificial gravity to the human system. Reduced physical activity, such as observed in microgravity or bed rest, has an effect on many physiological systems, such as the cardiovascular, musculoskeletal, immune, and body fluids regulation systems. There is currently no countermeasure that is effective to counteract both the cardiovascular and musculoskeletal deconditioning when applied for a short duration (see Chapter 1). Artificial gravity therefore seems the simplest physiological approach to keep these systems intact. The application of intermittent daily dose of artificial gravity by means of centrifugation has often been proposed as a potential countermeasure against the physiological deconditioning induced by spaceflight. However, neither the optimal gravity level, nor its optimal duration of exposure have been enough studied to recommend a validated, effective, and efficient artificial gravity application. As discussed in previous chapters, artificial gravity has a very high potential to counteract any changes caused by reduced physical activity. The nutrient supply, which ideally should match the actual needs, will interact with these changes and therefore has also to be taken into account. This chapter reviews the potential interactions between these nutrients (energy intake, vitamins, minerals) and the other physiological systems affected by artificial gravity generated by an on-board short-radius centrifuge.

Description: In several studies we tested the concepts that diet can alter acid-base balance and that reducing the dietary acid load has a positive effect on maintenance of bone. In study 1, (n = 11, 60-90 d bed rest), the renal acid load of the diet was estimated from its chemical composition, and was positively correlated with urinary markers of bone resorption (P less than 0.05); that is, the greater the acid load, the greater the excretion of bone resorption markers. In study 2, in males (n = 8, 30 d bed rest), an estimate of the ratio of nonvolatile acid precursors to base precursors in the diet was positively correlated (P less than 0.05) with markers of bone resorption. In study 3, for 28 d subjects received either a placebo (n = 6) or an essential amino acid supplement (n = 7) that included methionine, a known acid precursor. During bed rest (28 d), urinary calcium was greater than baseline levels in the supplemented group but not the control group (P less than 0.05), and in the supplemented group, urinary pH decreased (P less than 0.05). In study 4, less bone resorption occurred in space crew members who received potassium citrate (n = 6) during spaceflight of 4-6 months than in crew members who received placebo or were not in the study (n = 8) (P less than 0.05). Reducing acid load has the potential to mitigate increased bone resorption during spaceflight, and may serve as a bone loss countermeasure.

Description: Prolonged exposure in humans to a microgravity environment can lead to significant loss of bone and muscle mass, cardiovascular and sensory-motor deconditioning, and hormonal changes. These adaptive changes to weightlessness present a formidable obstacle to human exploration of space, particularly for missions requiring travel times of several months or more, such as on a trip to Mars. Countermeasures that address each of these body systems separately show only limited success. One possible remedy for this situation is artificial gravity, because it tackles all these systems across the board.

Description: Based on the summaries presented in the above sections of what is still to be learned on the effects of artificial gravity on human functions, this chapter will discuss the short- and long-term steps of research required to understand fundamentals and to validate operational aspects of using artificial gravity as an effective countermeasure for long-duration space travel.

Description: This chapter describes the pros and cons of artificial gravity applications in relation to human sensory-motor functioning in space. Spaceflight creates a challenge for sensory-motor functions that depend on gravity, which include postural balance, locomotion, eye-hand coordination, and spatial orientation. The sensory systems, and in particular the vestibular system, must adapt to weightlessness on entering orbit, and again to normal gravity upon return to Earth. During this period of adaptation, which persists beyond the actual gravity-level transition itself the sensory-motor systems are disturbed. Although artificial gravity may prove to be beneficial for the musculoskeletal and cardiovascular systems, it may well have negative side effects for the neurovestibular system, such as spatial disorientation, malcoordination, and nausea.

Description: Prolonged microgravity exposure disrupts natural bone remodeling processes and can lead to a significant loss of bone strength, increasing injury risk during missions and placing astronauts at a greater risk of bone fracture later in life. Resistance based exercise during missions is used to combat bone loss, but current exercise countermeasures do not completely mitigate the effects of microgravity. To address this concern, we present work to develop a personalizable, site-specific computational modeling tool chain of bone remodeling dynamics to understand and estimate changes in volumetric bone mineral density (BMD) in response to microgravityinduced bone unloading and in-flight exercise. The toolchain is evaluated against data collected from subjects in a 70-day bed rest study and is found to provide insight into the amount of exercise stimulus needed to minimize bone loss, quantitatively predicting post-study volumetric BMD of control subjects who did not perform exercise, and qualitatively predicting the effects of exercise. Results suggest that, with additional data, the toolchain could be improved to aid in developing customized in-flight exercise regimens and predict exercise effectiveness.

Description: The charts, that are the totality of this document, presents tasks, duration of the tasks, the start and finish of the tasks, and subtasks. Also presented are PERT charts that display the beginning, external milestones, and end points for the tasks, and sub tasks.

Description: This viewgraph presentation provides a review of NASA Johnson Space Center's Toxicology program. The mission of this program is to protect crews from toxic exposures during spaceflight. The presentation reviews some of the health hazards. A toxicological hazard level chart is presented that reviews the rating of hazard level, irritancy, systemic effects and containability. The program also participates in the Lunar Airborne Dust Toxicity Advisory Group.

Description: During lunar excursions in the EVA suit, real-time measurement of metabolic rate is required to manage consumables and guide activities to ensure safe return to the base. Metabolic rate, or oxygen consumption (VO2), is normally measured from pulmonary parameters but cannot be determined with standard techniques in the oxygen-rich environment of a spacesuit. Our group developed novel near infrared spectroscopic (NIRS) methods to calculate muscle oxygen saturation (SmO2), hematocrit, and pH, and we recently demonstrated that we can use our NIRS sensor to measure VO2 on the leg during cycling. Our NSBRI-funded project is looking to extend this methodology to examine activities which more appropriately represent EVA activities, such as walking and running and to better understand factors that determine the metabolic cost of exercise in both normal and lunar gravity. Our 4 year project specifically addresses risk: ExMC 4.18: Lack of adequate biomedical monitoring capability for Constellation EVA Suits and EPSP risk: Risk of compromised EVA performance and crew health due to inadequate EVA suit systems.

Description: Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have demonstrated that genes with upregulated expression induced by IR may play important roles in DNA damage sensing, cell cycle checkpoint and chromosomal repair, the relationship between the regulation of gene expression by IR and its impact on cytogenetic responses to ionizing radiation has not been systematically studied. In our present study, the expression of 25 genes selected based on their transcriptional changes in response to IR or from their known DNA repair roles were individually knocked down by siRNA transfection in human fibroblast cells. Chromosome aberrations (CA) and micronuclei (MN) formation were measured as the cytogenetic endpoints. Our results showed that the yield of MN and/or CA formation were significantly increased by suppressed expression of 5 genes that included Ku70 in the DSB repair pathway; XPA in the NER pathway; RPA1 in the MMR pathway; RAD17 and RBBP8 in cell cycle control. Knocked-down expression of 4 genes including MRE11A, RAD51 in the DSB pathway, and SESN1 and SUMO1 showed significant inhibition of cell cycle progression, possibly because of severe impairment of DNA damage repair. Furthermore, loss of XPA, p21 and MLH1 expression resulted in both enhanced cell cycle progression and significantly higher yield of cytogenetic damage, indicating the involvement of these gene products in both cell cycle control and DNA damage repair. Of these 11 genes that affected the cytogenetic response, 9 were up-regulated in the cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulating the biological consequences after IR. Failure to express these IR-responsive genes, such as by gene mutation, could seriously change the outcome of the post IR scenario and lead to carcinogenesis.

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: The goal of the present study was to investigate the adaptive effects of variation in the direction of optic flow, experienced during linear treadmill walking, on modifying locomotor trajectory. Subjects (n = 30) walked on a motorized linear treadmill at 4.0 km/h for 24 minutes while viewing the interior of a 3D virtual scene projected onto a screen 1.5 m in front of them. The virtual scene depicted constant self-motion equivalent to either 1) walking around the perimeter of a room to one s left (Rotating Room group) 2) walking down the center of a hallway (Infinite Hallway group). The scene was static for the first 4 minutes, and then constant rate self-motion was simulated for the remaining 20 minutes. Before and after the treadmill locomotion adaptation period, subjects performed five stepping trials where in each trial they marched in place to the beat of a metronome at 90 steps/min while blindfolded in a quiet room. The subject s final heading direction (deg), final X (for-aft, cm) and final Y (medio-lateral, cm) positions were measured for each trial. During the treadmill locomotion adaptation period subject s 3D torso position was measured. We found that subjects in the Rotating Room group as compared to the Infinite Hallway group: 1) showed significantly greater deviation during post exposure testing in the heading direction and Y position opposite to the direction of optic flow experienced during treadmill walking 2) showed a significant monotonically increasing torso yaw angular rotation bias in the direction of optic flow during the treadmill adaptation exposure period. Subjects in both groups showed greater forward translation (in the +X direction) during the post treadmill stepping task that differed significantly from their pre exposure performance. Subjects in both groups reported no perceptual deviation in position during the stepping tasks. We infer that 3 viewing simulated rotary self-motion during treadmill locomotion causes adaptive modification of sensory-motor integration in the control of position and trajectory during locomotion which functionally reflects adaptive changes in the integration of visual, vestibular, and proprioceptive cues. Such an adaptation in the control of position and heading direction during locomotion due to the congruence of sensory information demonstrates the potential for adaptive transfer between sensorimotor systems and suggests a common neural site for the processing and self-motion perception and concurrent adaptation in motor output. This will result in lack of subjects perception of deviation of position and trajectory during the post treadmill step test while blind folded.

Description: High-energy secondary neutrons, produced by the interaction of galactic cosmic rays with the atmosphere, spacecraft structure and planetary surfaces, contribute to a significant fraction to the dose equivalent in crew members and passengers during commercial aviation travel, and astronauts in space missions. The Los Alamos Nuclear Science Center (LANSCE) neutron facility#s ICE House 30L beamline is known to generate neutrons that simulate the secondary neutron spectra of earth#s atmosphere. The neutron spectrum is also similar to that measured onboard spacecraft like the MIR and International Space Station (ISS). To evaluate the biological damage, we exposed human fibroblasts in vitro to the LANSCE neutron beams without degrader at an entrance dose rate of 25 mGy/hr and analyzed the micronuclei (MN) induction. The cells were also placed behind a 9.9 cm water column to study effect of shielding in the protection of neutron induced damages. It was found that the dose response in the MN frequency was linear for the samples with and without shielding and the slope of the MN yield behind the shielding was reduced by a factor of 3.5. Compared to the MN induction in human fibroblasts exposed to a gamma source at a low dose rate, the RBE was found to be 16.7 and 10.0 for the neutrons without and with 9.9 cm water shielding, respectively.

Description: Clear vision and accurate localization of objects in the environment are prerequisites for reliable performance of motor tasks. Space flight confronts the crewmember with a stimulus rearrangement that requires adaptation to function effectively with the new requirements of altered spatial orientation and motor coordination. Adaptation and motor learning driven by the effects of cerebellar disorders may share some of the same demands that face our astronauts. One measure of spatial localization shared by the astronauts and those suffering from cerebellar disorders that is easily quantified, and for which a neurobiological substrate has been identified, is the control of the angle of gaze (the "line of sight"). The disturbances of gaze control that have been documented to occur in astronauts and cosmonauts, both in-flight and postflight, can be directly related to changes in the extrinsic gravitational environment and intrinsic proprioceptive mechanisms thus, lending themselves to description by simple non-linear statistical models. Because of the necessity of developing robust normal response populations and normative populations against which abnormal responses can be evaluated, the basic models can be formulated using normal, non-astronaut test subjects and subsequently extended using centrifugation techniques to alter the gravitational and proprioceptive environment of these subjects. Further tests and extensions of the models can be made by studying abnormalities of gaze control in patients with cerebellar disease. A series of investigations were conducted in which a total of 62 subjects were tested to: (1) Define eccentric gaze-holding parameters in a normative population, and (2) explore the effects of linear acceleration on gaze-holding parameters. For these studies gaze-holding was evaluated with the subjects seated upright (the normative values), rolled 45 degrees to both the left and right, or pitched back 30 and 90 degrees. In a separate study the further effects of acceleration on gaze stability was examined during centrifugation (+2 G (sub x) and +2 G (sub z) using a total of 23 subjects. In all of our investigations eccentric gaze-holding was established by having the subjects acquire an eccentric target (+/-30 degrees horizontal, +/- 15 degrees vertical) that was flashed for 750 msec in an otherwise dark room. Subjects were instructed to hold gaze on the remembered position of the flashed target for 20 sec. Immediately following the 20 sec period, subjects were cued to return to the remembered center position and to hold gaze there for an additional 20 sec. Following this 20 sec period the center target was briefly flashed and the subject made any corrective eye movement back to the true center position. Conventionally, the ability to hold eccentric gaze is estimated by fitting the natural log of centripetal eye drifts by linear regression and calculating the time constant (G) of these slow phases of "gaze-evoked nystagmus". However, because our normative subjects sometimes showed essentially no drift (tau (sub c) = m), statistical estimation and inference on the effect of target direction was performed on values of the decay constant theta = 1/(tau (sub c)) which we found was well modeled by a gamma distribution. Subjects showed substantial variance of their eye drifts, which were centrifugal in approximately 20 % of cases, and 〉 40% for down gaze. Using the ensuing estimated gamma distributions, we were able to conclude that rightward and leftward gaze holding were not significantly different, but that upward gaze holding was significantly worse than downward (p〈0.05). We also concluded that vertical gaze holding was significantly worse than horizontal (p〈0.05). In the case of left and right roll, we found that both had a similar improvement to horizontal gaze holding (p〈0.05), but didn't have a significant effect on vertical gaze holding. For pitch tilts, both tilt angles significantly decreased gaze-holding ility in all directions (p〈0.05). Finally, we found that hyper-g centrifugation significantly decreased gaze holding ability in the vertical plane. The main findings of this study are as follows: (1) vertical gaze-holding is less stable than horizontal, (2) gaze-holding to upward targets is less stable than to downward targets, (3) tilt affects gaze holding, and (4) hyper-g affects gaze holding. This difference between horizontal and vertical gaze-holding may be ascribed to separate components of the velocity-to-position neural integrator for eye movements, and to differences in orbital mechanics. The differences between upward and downward gaze-holding may be ascribed to an inherent vertical imbalance in the vestibular system. Because whole body tilt and hyper-g affects gaze-holding, it is implied that the otolith organs have direct connections to the neural integrator and further studies of astronaut gaze-holding are warranted. Our statistical method for representing the range of normal eccentric gaze stability can be readily applied to normals who maybe exposed to environments which may modify the central integrator and require monitoring, and to evaluate patients with gaze-evoked nystagmus by comparing to the above established normative criteria.

Description: Ground-based analogs of spaceflight are an important means of studying physiological and nutritional changes associated with space travel, particularly since exploration missions are anticipated, and flight research opportunities are limited. A clinical nutritional assessment of the NASA Extreme Environment Mission Operation V (NEEMO) crew (4 M, 2 F) was conducted before, during, and after the 14-d saturation dive. Blood and urine samples were collected before (D-12 and D-1), during (MD 7 and MD 12), and after (R + 0 and R + 7) the dive. The foods were typical of the spaceflight food system. A number of physiological changes were reported both during the dive and post dive that are also commonly observed during spaceflight. Serum hemoglobin and hematocrit were decreased (P less than 0.05) post dive. Serum ferritin and ceruloplasmin significantly increased during the dive, while transferring receptors tended to go down during the dive and were significantly decreased by the last day (R + 0). Along with significant hematological changes, there was also evidence for increased oxidative damage and stress during the dive. 8-hydroxydeoxyguanosine was elevated (P less than 0.05) during the dive, while glutathione peroxidase and superoxide disrnutase activities were decreased (P less than 0.05) during the dive. Serum C-reactive protein (CRP) concentration also tended to increase during the dive, suggesting the presence of a stress-induced inflammatory response, Decreased leptin during the dive (P less than 0.05) may also be related to the increased stress. Similar to what is observed during spaceflight, subjects had decreased energy intake and weight loss during the dive. Together, these similarities to spaceflight provide a model to further define the physiological effects of spaceflight and investigate potential countermeasures.

Description: An historical look at exploration medicine, upcoming missions and medical challenges, risk and spaceflight events, getting the medicine into the engineering system

Description: Prolonged microgravity exposure disrupts natural bone remodeling processes and can lead to a significant loss of bone strength, increasing injury risk during missions and placing astronauts at a greater risk of bone fracture later in life. Resistance-based exercise during missions is used to combat bone loss, but current exercise countermeasures do not completely mitigate the effects of microgravity. To address this concern, we present work to develop a personalizable, site-specific computational modeling toolchain of bone remodeling dynamics to understand and estimate changes in volumetric bone mineral density (BMD) in response to microgravity-induced bone unloading and in-flight exercise. The toolchain is evaluated against data collected from subjects in a 70-day bedrest study and is found to provide insight into the amount of exercise stimulus needed to minimize bone loss, quantitatively predicting post-study volumetric BMD of control subjects who did not perform exercise, and qualitatively predicting the effects of exercise. Results suggest that, with additional data, the toolchain could be improved to aid in developing customized in-flight exercise regimens and predict exercise effectiveness.

Description: An engineering evaluation was performed on the ExerGenie(r) exercise device to quantify its capabilities and limitations to address questions from the Constellation Program. Three subjects performed rowing and circuit training sessions to assess the suitability of the device for aerobic exercise. Three subjects performed a resistive exercise session to assess the suitability of the device for resistive exercise. Since 1 subject performed both aerobic and resistive exercise sessions, a total of 5 subjects participated.

Description: We have used cross-species multi-color banding (RxFISH) combined with telomere FISH probes, to measure chromosomal aberrations in the progeny of human peripheral blood lymphocytes exposed to ionizing radiation. Accelerated iron particles (energy 1 GeV/nucleon) induced many more terminal deletions than the same dose of gamma-rays. We found that truncated chromosomes without telomeres could be transmitted for at least three cell cycles following exposure, and represented about 10% of all aberrations observed in the progeny of cells exposed to iron ions. High energy heavy ions generate the most significant health risk for human space exploration and the results suggest that telomere loss may be the leading mechanism for their high efficiency in the induction of late effects.

Description: The purpose of this investigation was to determine the effect of different cadences on the ground reaction force (GRF(sub R)) during the squat exercise. It is known that squats performed with greater acceleration will produce greater inertial forces; however, it is not well understood how different squat cadences affect GRF(sub R). It was hypothesized that faster squat cadences will result in greater peak GRF(sub R). METHODS: Six male subjects (30.8+/-4.4 y, 179.5+/-8.9 cm, 88.8+/-13.3 kg) with previous squat experience performed three sets of three squats using three different cadences (FC = 1 sec descent/1 sec ascent; MC = 3 sec descent/1 sec ascent; SC = 4 sec descent/2 sec ascent) with barbell mass equal to body mass. Ground reaction force was used to calculate inertial force trajectories of the body plus barbell (FI(sub system)). Forces were normalized to body mass. RESULTS: Peak GRF(sub R) and peak FI(sub system) were significantly higher in FC squats compared to MC (p=0.0002) and SC (p=0.0002). Range of GRF(sub R) and FI(sub system) were also significantly higher in FC compared to MC (p〈0.05), and MC were significantly higher than SC (p〈0.05). DISCUSSION: Faster squat cadences result in significantly greater peak GRF(sub R) due to the inertia of the system. GRF(sub R) was more dependent upon decent cadence than on ascent cadence. PRACTICAL APPLICATION: This study demonstrates that faster squat cadences produce greater ground reaction forces. Therefore, the use of faster squat cadences might enhance strength and power adaptations to long-term resistance exercise training. Key Words: velocity, weight training, resistive exercise

Description: NASA is currently the leader, in conjunction with our Russian counterpart co-leads, of the Multilateral Medical Policy Board (MMPB), the Multilateral Medical Operations Panel (MMOP), which coordinates medical system support for International Space Station (ISS) crews, and the Multilateral Space Medicine Board (MSMB), which medically certifies all crewmembers for space flight on-board the ISS. These three organizations have representatives from NASA, RSA-IMBP (Russian Space Agency- Institute for Biomedical Problems), GCTC (Gagarin Cosmonaut Training Center), ESA (European Space Agency), JAXA (Japanese Space Agency), and CSA (Canadian Space Agency). The policy and strategic coordination of ISS medical operations occurs at this level, and includes interactions with MMOP working groups in Radiation Health, Countermeasures, Extra Vehicular Activity (EVA), Informatics, Environmental Health, Behavioral Health and Performance, Nutrition, Clinical Medicine, Standards, Post-flight Activities and Rehabilitation, and Training. Each ISS Expedition has a lead Crew Surgeon from NASA and a Russian Crew Surgeon from GCTC assigned to the mission. Day-to-day issues are worked real-time by the flight surgeons and biomedical engineers (also called the Integrated Medical Group) on consoles at the MCC (Mission Control Center) in Houston and the TsUP (Center for Flight Control) in Moscow/Korolev. In the future, this may also include mission control centers in Europe and Japan, when their modules are added onto the ISS. Private medical conferences (PMCs) are conducted regularly and upon crew request with the ISS crew via private audio and video communication links from the biomedical MPSR (multipurpose support room) at MCC Houston. When issues arise in the day-to-day medical support of ISS crews, they are discussed and resolved at the SMOT (space medical operations team) meetings, which occur weekly among the International Partners. Any medical or life science issue that is not resolved at the SMOT can be taken to the Mission Management Team meeting, which occurs biweekly from MCC-Houston. This meeting includes the other International Partners and all flight support and console position representatives via teleconference. ISS Crew Surgeons have handled many medical conditions on orbit; including skin rashes, dental abscesses, lacerations, and STT segment EKG changes. Fortunately to date, there have not been any forced medical evacuations from the ISS. This speaks well for the implementation of the primary, secondary and even tertiary prevention strategies invoked by the Integrated Medical Group, as there were several medical evacuations during the previous Russian space stations.

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: Dietary control and nutrient intake are critical aspects of any metabolic study, but this is especially true in the case of bed rest studies. We sought to define nutrient requirements, develop menus, and implement them in a series of three long-duration bed rest studies. With regard to energy intake, the goal was to maintain subject body weight to within 3% of their body weight on day 3 of bed rest (after fluid shift had occurred). For other nutrients, intakes were based on the NASA space flight nutritional requirements (with some adaptations based on the ground-based model used here). A secondary goal was to develop menus with foods similar to those expected to be approved for space flight (however, this was relaxed to attain desired nutrient intakes). This paper also describes the role of the research dietitian as part of the multi-disciplinary team and the importance of the metabolic kitchen staff. It also provides insight into some of the dietary challenges that arise during extended-duration bed rest studies. Regardless of the overall objective of the study, nutrition must be carefully planned, implemented, and monitored for results to be uncompromised.

Description: Because NASA's approach to space exploration calls for long-term extended missions, there is a pressing need to equip astronauts with effective exercise regimens that will maintain musculoskeletal and cardiovascular health. ZIN Technologies, Inc., has developed an innovative miniature treadmill for use in both zero-gravity and terrestrial environments. The treadmill offers excellent periodic impact exercise to stimulate cardiovascular activity and bone remodeling as well as resistive capability to encourage full-body muscle maintenance. A novel speed-control algorithm allows users to modulate treadmill speed by adjusting stride, and a new subject load device provides a more Earth-like gravity replacement load. This new and compact treadmill offers a unique approach to managing astronaut health while addressing the inherent and stringent challenges of space flight. The innovation also has the potential to offer numerous terrestrial applications, as a real-time daily load stimulus (DLS) measurement feature provides an effective mechanism to combat or manage osteoporosis, a major public health threat for 55 percent of Americans over the age of 50.

Description: Spaceflight perturbs the human immune system. Among other manifestations, crewmembers may experience latent herpes viruses reactivation due to impaired lymphocyte function, as well as allergic/hypersensitivity reactions. Considering future space travel will be of longer duration (thereby increasing stress, exposure to radiation, etc) with no rapid return option, it is of paramount importance to develop a countermeasure(s) to immune dysregulation. Monophosphoryl lipid A (MPLA) is a derivative of lipopolysaccharide (LPS), a potent inflammatory agent that can cause septic shock. MPLA possesses the immune-stimulatory effects of LPS without the adverse inflammatory effects. We hypothesize that treating immune cells with MPLA will boost their function enough to overcome the inhibitory effects of microgravity. While MPLA has been tested as an adjuvant extensively in mice and preliminarily for human vaccines, it has never been assessed for efficacy in microgravity.

Description: The Portable Test System (PTS) is a hand-held device for monitoring the presence of potentially hazardous bacteria in the environment. It uses an immunological method derived from the horseshoe crab (Limulus polyphemus) to detect bacterial cell membranes and other molecular components of a cell. Further modifications of the PTS will allow detection of individual hazardous species of bacteria. This study was a follow-up of previous PTS and other immunological tests performed on the KC-135 during 2002-2003 (Maule et al., 2003, J. Gravit. Physiol.) and in the underwater habitat Aquarius during NEEMO 5 (Maule et al., 2005, Appl. Environ. Microbiol in prep.). The experiments described here were part of a final testing phase prior to use of the PTS on the International Space Station (ISS), scheduled for launch on 12A.1 on February 9th 2006. The specific aspects of PTS operation studied were those involving a fluid component: pumping, mixing, incubations and pipetting into the instrument. The PTS uses a stepper motor to move fluid along small channels, which may be affected by reduced gravity.

Description: A spaceflight-compatible flow cytometer would be useful for the diagnosis of astronaut illness during long duration spaceflight and for conducting in-flight research to evaluate the effects of microgravity on human physiology. Until recently, the primary limitations preventing the development of a spaceflight compatible flow cytometer have been largely mechanical. Standard commercially available flow cytometers are large, complex instruments that use high-energy lasers and require significant training to operate. Standard flow cytometers function by suspending the particles to be analyzed inside a sheath fluid for analysis. This requires the presence of several liters of sheath fluid for operation, and generates a corresponding amount of liquid hazardous waste. The particles are then passed through a flow cell which uses the fluid mechanical property of hydrodynamic focusing to place the cells in single-file (laminar flow) as they pass through a laser beam for scanning and evaluation. Many spaceflight experiments have demonstrated that fluid physics is dramatically altered in microgravity (MSF [Manned Space Flight] Fluid Physics Data Sheet-August 1997) and previous studies have shown that sheath-fluid based hydrodynamic focusing may also be altered during microgravity (Crucian et al, 2000). For these reasons it is likely that any spaceflight compatible design for a flow cytometer would abandon the sheath fluid requirement. The elimination of sheath fluid would remove both the problems of weight associated with large volumes of liquids as well as the large volume of liquid waste generated. It would also create the need for a method to create laminar particle flow distinct from the standard sheath-fluid based method. The spaceflight prototype instrument is based on a recently developed commercial flow cytometer possessing a novel flow cell design that creates single-particle laser scanning and evaluation without the need for sheath-fluid based hydrodynamic focusing. This instrument also possesses a number of design advances that make it conditionally microgravity compatible: it is highly miniaturized and lightweight, uses a low energy diode laser, has a small number of moving parts, does not use sheath fluid and does not generate significant liquid waste. Although possessing certain limitations, the commercial cytometer functions operationally like a standard bench top laboratory flow cytometer, aspirating liquid particle samples and generating histogram or dot-plot data in standard FCS file format. In its current configuration however, the cytometer is limited to three parameter/two-color capability (two color PMTs + forward scatter), does not allow compensation between colors, does not allow linear analysis and is operated by rather inflexible software with limited capabilities. This is due to the fact that the cytometer has been designed and marketed as an instrument specific to a few particular assays, not as a multipurpose cytometer.

Description: Prior to the human exploration of Mars or long duration stays on the Earth s moon, the risk of cancer and other diseases from space radiation must be accurately estimated and mitigated. Space radiation, comprised of energetic protons and heavy nuclei, has been show to produce distinct biological damage compared to radiation on Earth, leading to large uncertainties in the projection of cancer and other health risks, while obscuring evaluation of the effectiveness of possible countermeasures. Here, we describe how research in cancer radiobiology can support human missions to Mars and other planets.

Description: There is ample evidence to suggest that space flight leads to immune system dysregulation. This may be a result of microgravity, confinement, physiological stress, radiation, environment or other mission-associated factors. It is attractive to utilize ground-based spaceflight analogs as appropriate to investigate this phenomenon. For spaceflight-associated immune dysregulation (SAID), the authors believe the most appropriate analogs might be NEEMO (short duration, Shuttle analog), Antarctic winter-over (long-duration, ISS analog) and the Haughton Mars Project in the Canadian Arctic (intermediate-duration). Each of these analogs replicate isolation, mission-associated stress, disrupted circadian rhythms, and other aspects of flight thought to contribute to SAID. To validate NEEMO as a flight analog with respect to SAID, a pilot study was conducted during the NEEMO-12 and 13 missions during 2007. Assays were performed that assessed immune status, physiological stress and latent viral reactivation. Blood and saliva samples were collected at pre-, mid-, and post-mission timepoints.

Description: This review summarizes what has been learned from studies of human neurovestibular system in weightless conditions, including balance and locomotion, gaze control, vestibular-autonomic function and spatial orientation, and gives some examples of the potential Earth benefits of this research. Results show that when astronauts and cosmonauts return from space flight, both the peripheral and central neural processes are physiologically and functionally altered. There are clear distinctions between the virtually immediate adaptive compensations to weightlessness and those that require longer periods of time to adapt. However, little is known to date about the adaptation of sensory-motor functions to long-duration space missions in weightlessness and to the transitions between various reduced gravitational levels, such as on the Moon and Mars. Results from neurovestibular research in space have substantially enhanced our understanding of the mechanisms and characteristics of postural, gaze, and spatial orientation deficits, analogous to clinical cases of labyrinthine-defective function. Also, space neurosciences research has participated in the development and application of significant new technologies, such as video recording and processing of three-dimensional eye movements and posture, hardware for the unencumbered measurement of head and body movement, and procedures for investigating otolith function on Earth. In particular, devices such as centrifugation or off-vertical axis rotation could enhance clinical neurological testing because it provides linear acceleration which specifically stimulates the otolith organs in a frequency range close to natural head and body movement.

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: Ionizing radiation is a major health risk of long-term space travel, the biological consequences of which include genetic and oxidative damage. In this study, we propose an original mechanism by which high doses of ionizing radiation induce acute toxicity. We identified biological components that appear in the lymphatic vessels shortly after gamma irradiation. These radiation-induced toxins, which we have named specific radiation determinants (SRD), were generated in the irradiated tissues and then collected and circulated throughout the body via the lymph circulation and bloodstream. Depending on the type of SRD elicited, different syndromes of acute radiation sickness (ARS) were expressed. The SRDs were developed into a vaccine used to confer active immunity against acute radiation toxicity in immunologically naive animals. Animals that were pretreated with SRDs exhibited resistance to lethal doses of gamma radiation, as measured by increased survival times and survival rates. In comparison, untreated animals that were exposed to similar large doses of gamma radiation developed acute radiation sickness and died within days. This phenomenon was observed in a number of mammalian species. We partially analyzed the biochemical characteristics of the SRDs. The SRDs were large molecular weight (200-250 kDa) molecules that were comprised of a mixture of protein, lipid, carbohydrate, and mineral. Further analysis is required to further identify the SRD molecules and the biological mechanism by which the mediate the toxicity associated with acute radiation sickness. By doing so, we may develop an effective specific immunoprophylaxis as a countermeasure against the acute effects of ionizing radiation.

Description: Dysregulation of the immune system has been shown to occur during space flight, although the detailed nature of the phenomenon and the clinical risks for exploration class missions has yet to be established. In addition, the growing clinical significance of immune system evaluation combined with epidemic infectious disease rates in third world countries provides a strong rationale for the development of field-compatible clinical immunology techniques and equipment. In July 2002 NASA performed a comprehensive field immunology assessment on crewmembers participating in the Haughton-Mars Project (HMP) on Devon Island in the high Canadian Arctic. The purpose of the study was to evaluate mission-associated effects on the human immune system, as well as to evaluate techniques developed for processing immune samples in remote field locations. Ten HMP-2002 participants volunteered for the study. A field protocol was developed at NASA-JSC for performing sample collection, blood staining/processing for immunophenotype analysis, wholeblood mitogenic culture for functional assessments and cell-sample preservation on-location at Devon Island. Specific assays included peripheral leukocyte distribution; constitutively activated T cells, intracellular cytokine profiles and plasma EBV viral antibody levels. Study timepoints were L-30, midmission and R+60. The protocol developed for immune sample processing in remote field locations functioned properly. Samples were processed in the field location, and stabilized for subsequent analysis at the Johnson Space Center in Houston. The data indicated that some phenotype, immune function and stress hormone changes occurred in the HMP field participants that were largely distinct from pre-mission baseline and post-mission recovery data. These immune changes appear similar to those observed in Astronauts following spaceflight. The sample processing protocol developed for this study may have applications for immune assessment during exploration-class space missions or in remote terrestrial field locations. The data validate the use of the HMP as a ground-based spaceflight/planetary exploration analog for some aspects of human physiology.

Description: Induction of cataracts by occupational exposure in flight crew has been an important topic of interest in aerospace medicine in the past five years, in association with numerous reports of flight-associated disease incidences. Due to numerous confounding variables, it has been difficult to determine if there is increased cataract risk directly caused by interaction with the flight environment, specifically associated with added radiation exposure during flight. Military aviator records from the United States Air Force (USAF) and Navy (USN) and US astronauts at the National Aeronautics and Space Administration (NASA)/Lyndon B. Johnson Space Center (JSC) were evaluated for the presence, location and age of diagnosis of cataracts. Military aviators were found to have a statistically significant younger average age of onset of their cataracts compared with astronauts, however the incidence density of cataracts was found to be statistically higher in astronauts than in military aviators. USAF and USN aviator s cataracts were most commonly located in the posterior subcapsular region of the lens while astronauts cataracts were most likely to originate generally in the cortical zone. A prospective clinical trial which controls for confounding variables in examination technique, cataract classification, diet, exposure, and pharmacological intervention is needed to determine what percentage of the risk for cataracts are due to radiation, and how to best develop countermeasures to protect flight crews from radiation bioeffects in the future.

Description: The prospect of a lunar outpost to conduct science and learn how to live and work off the Earth is exciting. The nutritional sciences will focus on the issues of over all health, with emphasis on skeletal muscle health and prevention of radiation damage. There is a great deal of research needed to determine the nutritional and food component potential for preventing the changes that occur in space flight. Further research is also needed on the interactions of systems and countermeasures, such as protein-amino acid needs for enhancement of muscle protein synthesis while not being detrimental for bone health. The interrelationship between radiation exposure, nutrition, and food components has just begun.

Description: Overall, the results obtained in both the U.S. and the Russian space programs indicate that most space crews will experience some symptoms of motion sickness (MS) causing significant impact on the operational objectives that must be accomplished to assure mission success. At this time the primary countermeasure for MS requires the administration of Promethazine. Promethazine is not a benign drug, and is most frequently administered just prior to the sleep cycle to prevent its side effects from further compromising mission objectives. Clearly other countermeasures for SMS must be developed. Currently the primary focus is on two different technologies: (1) developing new and different pharmacological compounds with less significant side effects, (2) preflight training. The primary problem with all of these methods for controlling MS is time. New drugs that may be beneficial are years from testing and development, and preflight training requires a significant investment of crew time during an already intensive pre-launch schedule. Granted, motion sickness symptoms can be minimized with either of the two methods detailed above, however, it may be possible to develop a countermeasure that does not require either extensive adaptation time or exposure to motion sickness. Approximately 25 years ago Professor Geoffrey Melvill Jones presented his work on adaptation of the vestibuloocular reflex (VOR) using optically reversed vision (left-right prisms) during head rotations in the horizontal plane. It was of no surprise that most subjects experienced motion sickness while wearing the optically reversing prisms. However, a serendipitous finding emerged during this research showing that the same subjects did not experience motion sickness symptoms when wearing the reversing prisms under stroboscopic illumination. The mechanism, by which this side-effect was believed to have occurred, is not clearly understood. However, the fact that no motion sickness was ever noted, suggests the possibility of producing functionally useful adaptation during space flight without the penalty of disabling motion sickness by controlling the rate of the adaptive process by means of an appropriate stroboscopically presented environment. After several recent meetings with Professor Melvill Jones, we were encouraged to repeat the motion sickness portions of his and Mandl's 1981 stroboscopic experiment. In conducting this experiment we used a randomized cross-over design where subjects were randomly assigned to either a stroboscopic flash or no strobe for their first exposure in the experimental design. Twenty subjects (19 subjects completed the study) read a short passage from Treasure Island mounted on the wall approximately 1 m from their eyes while wearing left-right reversing prisms. The strobe on time of 3 microseconds and flash frequency of 4 Hz was set to equal that used in the original study. Motion sickness was scored using a modified Miller and Graybiel scale that we constructed to include symptoms that may be elicited under conditions where reversing prisms are worn. On this scale a score of 5 represented Malaise IIa (mild motion sickness) and a score of 8 or above is approaching frank sickness. Symptoms were tracked and recorded every 5 min during the task. Testing was limited to 30 min unless the subject had reached the MIIa score, at which time the test was terminated. Performance under stroboscopic illumination was significantly better than when the subjects read under normal room illumination while wearing the left-right reversing prisms. Based on these results we developed a goggle system using LCD material that can be strobed. To evaluate the effectiveness of stroboscopic goggles we tested an additional 9 subjects in addition to retesting 10 used in the stroboscopic pilot study described above. These 19 subjects wore a pair of strobing LCD goggles that could be cycled at 4 Hz. These subjects wore the goggles while also wearing left-right reversg prisms. Results while wearing the goggles showed that none of the 19 subjects scored at the MIIa level on the motion sickness rating scale. When the goggles did not flash (no strobe), 11 of the 19 developed symptoms above the MIIa criteria. As a countermeasure the goggles seem to be effective, even with an on time of 10 msec (time the goggles are clear). We have also collected anecdotal data, from our personnel in the Neuroscience Laboratory at the Johnson Space Center, suggesting that the goggles may effective in preventing carsickness.

Description: This slide presentation reviews the Functional Task Test (FTT), an interdisciplinary testing regimen that has been developed to evaluate astronaut postflight functional performance and related physiological changes. The objectives of the project are: (1) to develop a set of functional tasks that represent critical mission tasks for the Constellation Program, (2) determine the ability to perform these tasks after space flight, (3) Identify the key physiological factors that contribute to functional decrements and (4) Use this information to develop targeted countermeasures.

Description: This viewgraph presentation reviews some of the challenges that spaceflight imposes on the Human system. It describes four of the signs and symptoms of fluid shift in the astronaut when they fly in low earth orbit. It describes how the leg muscles influence blood flow It also outlines the four phases of "fluid shift" and where the majority of the central volume of blood is located in the body And it reviews other changes to the body systems as a result of Fluid Shift

Description: No abstract available

Description: This document reviews NASA's Exploration Medical Capability (ExMC) program. The new space exploration program, outlined by the President will present new challenges to the crew's health. The project goals are to develop and validate requirements for reliable, efficient, and robust medical systems and treatments for space exploration to maximize crew performance for mission objectives.

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 biomechanics of exercise in space is difficult to study and there are unknowns surrounding exercise performance on future space exploration countermeasures systems. These issues are beginning to be addressed through enhanced modeling techniques fueled initially by human-in-the-loop data collections in ground-based environments. The presentation will focus on an effort completed at the University of South Florida to apply the Computer Assisted Rehabilitation Environment (CAREN) system to address a human spaceflight need. The research explored the interaction between a human and a moving platform while exercise was completed.

Description: While astronauts are returning from long duration spaceflight with multiple ocular signs that mimic those seen in terrestrial patients with elevated intracranial pressure (ICP), evidence has yet to prove a clinically significant increase in ICP during space.1 Preliminary research evidence may even suggest that ICP decreases in microgravity. Idiopathic intracranial hypertension (IIH) has long been considered the ideal terrestrial analogue to Spaceflight Associated Neuro-ocular Syndrome (SANS).1 However, there are several critical features of SANS that do not complement any reported case of IIH on Earth. These findings mandate a closer look at the accuracy of IIH as a terrestrial SANS analog.

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

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

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

Description: Vision changes identified in long duration spaceflight astronauts has led Space Medicine at NASA to adopt a more comprehensive clinical monitoring protocol. Optical Coherence Tomography (OCT) was recently implemented at NASA, including on board the International Space Station in 2013. NASA is collaborating with Heidelberg Engineering to increase the fidelity of the current OCT data set by integrating the traditional circumpapillary OCT image with radial and horizontal block images at the optic nerve head. The retinal nerve fiber layer was segmented by two experienced individuals. Intra-rater (N=4 subjects and 70 images) and inter-rater (N=4 subjects and 221 images) agreement was performed. The results of this analysis and the potential benefits will be presented.

Description: The purpose of this pilot study is to investigate the collection, preparation, and analysis of tear biomarkers as a means of assessing ocular, neurological, and immunological health. At present, no published data exists on the cytokine profiles of tears from astronauts exposed to long periods of microgravity and space irradiations. In addition, no published data exist on cytokine (biomarker) profiles of tears that have been collected from irradiated non-human biological systems (primates and other animal models). A goal for the proposed pilot study is to discover novel tear biomarkers which can help inform researchers, clinicians, epidemiologist and healthcare providers about the health status of a living biological system, as well as informing them when a disease state is triggered. This would be done via analysis of the onset of expression of pro-inflammatory cytokines, leading up to the full progression of a disease (i.e. cancer, loss of vision, radiation-induced oxidative stress, cardiovascular disorders, fibrosis in major organs, bone loss). Another goal of this pilot study is to investigate the state of disease against proposed medical countermeasures, in order to determine whether the countermeasures are efficacious in preventing or mitigating these injuries. An example of an up and coming tear biomarker technology, Ascendant Dx, a clinical stage diagnostic company, is developing a screening test to detect breast cancer using proteins from tears. The team utilized Liquid Chromatography -Mass Spectrometry with Mass analysis (LC MS/MS) as a discovery platform followed by validation with ELISA to come up with a panel of protein biomarkers that can differentiate breast cancer samples from control ("cancer free") samples with results far surpassing the results of imaging techniques in use today. Continued research into additional proteins is underway to increase the sensitivity and specificity of the test and development efforts are on the way to transfer the test onto a fast, accurate and inexpensive point of care platform. In conclusion, the expected results from this proposed pilot study are to: a) establish an SOP for retrieving/storing/transporting tear fluid samples from multicentre sites b) establish a normal range for relevant biomarkers in tears; and c) establish a database (biobank) of tears of space nave versus veteran astronauts, to establish a personal baseline for long-term ocular health monitoring

Description: The International Space Station Medical Projects (ISSMP) Element provides planning, integration, and implementation services for HRP research studies for both spaceflight and flight analog research. Through the implementation of these two efforts, ISSMP offers an innovative way of guiding research decisions to meet the unique challenges of understanding the human risks to space exploration. Flight services provided by ISSMP include leading informed consent briefings, developing and validating in-flight crew procedures, providing ISS crew and ground-controller training, real-time experiment monitoring, on-orbit experiment and hardware operations and facilitating data transfer to investigators. For analog studies at the NASA Human Exploration Research Analog (HERA), the ISSMP team provides subject recruitment and screening, science requirements integration, data collection schedules, data sharing agreements, mission scenarios and facilities to support investigators. The ISSMP also serves as the HRP interface to external analog providers including the :envihab bed rest facility (Cologne, Germany), NEK isolation chamber (Moscow, Russia) and the Antarctica research stations. Investigators working in either spaceflight or analog environments requires a coordinated effort between NASA and the investigators. The interdisciplinary nature of both flight and analog research requires investigators to be aware of concurrent research studies and take into account potential confounding factors that may impact their research objectives. Investigators must define clear research requirements, participate in Investigator Working Group meetings, obtain human use approvals, and provide study-specific training, sample and data collection and procedures all while adhering to schedule deadlines. These science requirements define the technical, functional and performance operations to meet the research objectives. The ISSMP maintains an expert team of professionals with the knowledge and experience to guide investigators science through all aspects of mission planning, crew operations, and research integration. During this session, the ISSMP team will discuss best-practices approaches for successfully preparing and conducting studies in both the flight and analog environments. Critical tips and tricks will be shown to greatly improve your chances of successfully completing your research aboard the International Space Station and in Spaceflight Analogs.

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

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

Description: This fall, I was fortunate enough to have been able to participate in an internship at NASA's Lyndon B. Johnson Space Center. I was placed into the Human Health & Performance Directorate, where I was specifically tasked to work with Dr. Zarana Patel, researching the impacts of cosmic level radiation on human cells. Using different laboratory techniques, we were able to examine the cells to see if any damage had been done due to radiation exposure, and if so, how much damage was done. Cell culture samples were exposed at different doses, and fixed at different time points so that we could accumulate a large pool of quantifiable data. After examining quantifiable results relative to the impacts of space radiation on the human body at the cellular and chromosomal level, researchers can defer to different areas of the space program that have to do with astronaut safety, and research and development (extravehicular mobility unit construction, vehicle design and construction, etc.). This experience has been very eye-opening, and I was able to learn quite a bit. I learned some new laboratory techniques, and I did my best to try and learn new ways to balance such a hectic work and school schedule. I also learned some very intimate thing about working at NASA; I learned that far more people want to watch you succeed, rather than watch you fail, and I also learned that this is a place that is alive with innovators and explorers - people who have a sole purpose of exploring space for the betterment of humanity, and not for any other reason. It's truly inspiring. All of these experiences during my internship have impacted me in a really profound way, so much that my educational and career goals are completely different than when I started. I started out as a biotechnology major, and I discovered recently toward the end of the internship, that I don't want to work in a lab, nor was I as enthralled by biological life sciences as a believed myself to be. Taking that all into consideration, I've actually changed my major to mechanical engineering. I discovered that I enjoy building things, and I enjoy learning about materials and interactions between different things. And I quickly became obsessed with rocket and aerospace engineering, so I've decided that after a mechanical engineering degree, I will be pursuing an advanced degree in aerospace engineering. One final way that I was effected by this internship, is that I discovered that I don't want to have a career at NASA. I love this agency with all of my heart, but I refuse to allow my innovation to be bound by a scientifically illiterate congress. As such, I have decided to pursue commercial aerospace companies, such as Space, XCOR, Masten Space Systems, Orbital ATK, and many, many, more. Maybe one day I'll end up back here. I believe in what this agency is doing with my whole heart, and it's unfortunate to see them curtailed in some capacities as a result of budgetary constraints, brought on by people who don't fully understand the effort behind putting people in to space. All in all, this experience has been the best experience of my life - literally a childhood dream came true during this experience - and I cannot adequately explain how grateful I am to have been here for the past sixteen weeks.

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

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

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

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

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

Description: BACKGROUND: Coordinated locomotion has proven to be challenging for many astronauts following long duration spaceflight. As NASA's vision for spaceflight points toward interplanetary travel, we must prepare for unassisted landings, where crewmembers may need to perform mission critical tasks within minutes of landing. Thus, it is vital to develop a knowledge base from which operational guidelines can be written that define when astronauts can be expected to safely perform certain tasks. Data obtained during the Field Test experiment (FT) will add important insight to this knowledge base. Specifically, we aim to develop a recovery timeline of functional sensorimotor performance during the first 24 hours and several days after landing. METHODS: FT is an ongoing study of 30 long-duration ISS crewmembers. Thus far, 9 have completed the full FT (5 U.S. Orbital Segment [USOS] astronauts and 4 Russian cosmonauts) and 4 more consented and launching within the next year. This is in addition to the eighteen crewmembers that participated in the pilot FT (11 USOS and 7 Russian crewmembers). The FT is conducted three times preflight and three times during the first 24 hours after landing. All crewmembers were tested in Kazakhstan in either the medical tent at the Soyuz landing site (~one hour post-landing), or at the airport (~four hours post-landing). The USOS crewmembers were also tested at the refueling stop (~12 hours post-landing) and at the NASA Johnson Space Center (~24 hours post-landing) and a final session 7 days post-landing. Crewmembers are instrumented with 9 inertial measurement unit sensors that measure acceleration and angular displacement (APDM's Emerald Sensors) and foot pressure-sensing insoles that measure force, acceleration, and center of pressure (Moticon GmbH, Munich, Germany) along with heart rate and blood pressure recording instrumentation. The FT consists of 12 tasks, but here we will focus on the most challenging task, the Tandem Walk, which was also performed as part of pilot FT. To perform the Tandem Walk, subjects begin with their feet together, their arms crossed at their chest and eyes closed. When ready, they brought one foot forward and touched the heel of their foot to their toe, repeating with the other foot, and continuing for about 10 steps. Three trials were collected with the eyes closed and a fourth trial was collected with eyes open. There are four metrics which are used to determine the performance level of the Tandem Walk. The first is percent correct steps. For a step to be counted as correct, the foot could not touch the ground while bringing it forward (no side stepping), eyes must stay closed during the eyes closed trials, the heel and toe should be touching, or almost touching (no large gaps) and there shouldn't be more than a three second pause between steps. Three judges score each step and the median of the three scores is kept. The second metric is the average step speed, or the number of steps/time to complete them. Thirdly, the root mean squared (RMS) error in the resultant trunk acceleration is used to determine the amount of upper body instability observed during the task. Finally, the RMS error of the mediolateral center of pressure as measured by the Moticon insoles is used to determine the mediolateral instability at the foot level. These four parameters are combined into a new overall Tandem Walk Parameter. RESULTS: Preliminary results show that crewmembers perform the Tandem Walk significantly worse the first 24 hours after landing as compared to their baseline performance. We find that each of the four performance metrics is significantly worse immediately after landing. We will present the results of tandem walk performance during the FT thus far. We will also combine these with the 18 crewmembers that participated in the pilot FT, concentrating on the level of performance and recovery rate. CONCLUSION: The Tandem Walk data collected as part of the FT experiment will provide invaluable information on the performance capabilities of astronauts during the first 24 hours after returning from long-duration spaceflight that can be used in planning future Mars, or other deep-space missions with unassisted landings. FT will determine the average sensorimotor recovery timeline and inform return-to-duty guidelines for unassisted landings.