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The field of human space travel is in the midst of a dramatic revolution. Upcoming missions are looking to push the boundaries of space travel, with plans to travel for longer distances and durations than ever before. Both the National Aeronautics and Space Administration (NASA) and several commercial space companies (e.g., Blue Origin, SpaceX, Virgin Galactic) have already started the process of preparing for long-distance, long-duration space exploration and currently plan to explore inner solar planets (e.g., Mars) by the 2030s. With the emergence of space tourism, space travel has materialized as a potential new, exciting frontier of business, hospitality, medicine, and technology in the coming years. However, current evidence regarding human health in space is very limited, particularly pertaining to short-term and long-term space travel. This review synthesizes developments across the continuum of space health including prior studies and unpublished data from NASA related to each individual organ system, and medical screening prior to space travel. We categorized the extraterrestrial environment into exogenous (e.g., space radiation and microgravity) and endogenous processes (e.g., alteration of humans' natural circadian rhythm and mental health due to confinement, isolation, immobilization, and lack of social interaction) and their various effects on human health. The aim of this review is to explore the potential health challenges associated with space travel and how they may be overcome in order to enable new paradigms for space health, as well as the use of emerging Artificial Intelligence based (AI) technology to propel future space health research.

Background: Thrombosis of the left internal jugular vein in an astronaut aboard the International Space Station was recently described, incidentally discovered during a research study of blood flow in neck veins in microgravity. Given this event, and the high incidence of flow abnormalities, the National Aeronautics and Space Administration (NASA) instituted an occupational surveillance program to evaluate astronauts for venous thrombosis., Methods: Duplex ultrasound of the bilateral internal jugular veins was conducted on all NASA astronauts terrestrially, and at three points during spaceflight. Respiratory maneuvers were performed. Images were analyzed for thrombosis and certain hemodynamic characteristics, including peak velocity and degree of echogenicity., Results: Eleven astronauts were evaluated with matching terrestrial and in-flight ultrasounds. No thrombosis was detected. Compared to terrestrial ultrasound measurements, in-flight peak velocity was reduced and lowest in the left. Six of 11 astronauts had mild-moderate echogenicity in the left internal jugular vein during spaceflight, but none had more than mild echogenicity in the right internal jugular vein. Two astronauts developed retrograde blood flow in the left internal jugular vein., Conclusion: Abnormal flow characteristics in microgravity, most prominent in the left internal jugular vein, may signal an increased risk for thrombus formation in some individuals.

Determining the extent of bone recovery after prolonged spaceflight is important for understanding risks to astronaut long-term skeletal health. We examined bone strength, density, and microarchitecture in seventeen astronauts (14 males; mean 47 years) using high-resolution peripheral quantitative computed tomography (HR-pQCT; 61 μm). We imaged the tibia and radius before spaceflight, at return to Earth, and after 6- and 12-months recovery and assessed biomarkers of bone turnover and exercise. Twelve months after flight, group median tibia bone strength (F.Load), total, cortical, and trabecular bone mineral density (BMD), trabecular bone volume fraction and thickness remained - 0.9% to - 2.1% reduced compared with pre-flight (p ≤ 0.001). Astronauts on longer missions (> 6-months) had poorer bone recovery. For example, F.Load recovered by 12-months post-flight in astronauts on shorter (< 6-months; - 0.4% median deficit) but not longer (- 3.9%) missions. Similar disparities were noted for total, trabecular, and cortical BMD. Altogether, nine of 17 astronauts did not fully recover tibia total BMD after 12-months. Astronauts with incomplete recovery had higher biomarkers of bone turnover compared with astronauts whose bone recovered. Study findings suggest incomplete recovery of bone strength, density, and trabecular microarchitecture at the weight-bearing tibia, commensurate with a decade or more of terrestrial age-related bone loss., (© 2022. The Author(s).)

Objectives: Bone loss remains a primary health concern for astronauts, despite in-flight exercise. We examined changes in bone microarchitecture, density and strength before and after long-duration spaceflight in relation to biochemical markers of bone turnover and exercise., Methods: Seventeen astronauts had their distal tibiae and radii imaged before and after space missions to the International Space Station using high-resolution peripheral quantitative CT. We estimated bone strength using finite element analysis and acquired blood and urine biochemical markers of bone turnover before, during and after spaceflight. Pre-flight exercise history and in-flight exercise logs were obtained. Mixed effects models examined changes in bone and biochemical variables and their relationship with mission duration and exercise., Results: At the distal tibia, median cumulative losses after spaceflight were -2.9% to -4.3% for bone strength and total volumetric bone mineral density (vBMD) and -0.8% to -2.6% for trabecular vBMD, bone volume fraction, thickness and cortical vBMD. Mission duration (range 3.5-7 months) significantly predicted bone loss and crewmembers with higher concentrations of biomarkers of bone turnover before spaceflight experienced greater losses in tibia bone strength and density. Lower body resistance training volume (repetitions per week) increased 3-6 times in-flight compared with pre-spaceflight. Increases in training volume predicted preservation of tibia bone strength and trabecular vBMD and thickness., Conclusions: Findings highlight the fundamental relationship between mission duration and bone loss. Pre-flight markers of bone turnover and exercise history may identify crewmembers at greatest risk of bone loss due to unloading and may focus preventative measures., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose of Review: Within the last decade, it was realized that during and after long-duration spaceflight, some astronauts experience ophthalmic abnormalities including refractive changes, optic disc edema, globe flattening, choroidal folds, and cotton wool spots. Much research has been initiated and conducted, but little evidence is available to differentiate affected crewmembers., Recent Findings: The first published data to distinguish between affected and nonaffected crewmembers identified biochemical differences in affected astronauts: one-carbon pathway metabolite concentrations were higher in these individuals than in nonaffected astronauts, even before flight. These data led to findings that genetics and B-vitamin status were predictors of the incidence of the ophthalmic abnormalities. A multihit hypothesis was developed, with genetics and B-vitamin status as two of several important elements that all contribute to endothelial dysfunction and ultimately to ophthalmic changes after flight. One of these contributing factors - response to carbon dioxide exposure - was recently documented to be affected by the same one-carbon pathway genetics., Summary: This line of research may help identify which astronauts are at risk of these ophthalmic changes, and allow targeted treatment. This research may have implications for clinical populations, including patients with polycystic ovary syndrome, that have similar biochemical, endocrine, and genetic characteristics, and it may shed light on why links between cardiovascular disease and the metabolites homocysteine and folate have been elusive and confounded.

Background: Bed rest studies document that a lower dietary acid load is associated with lower bone resorption., Objective: We tested the effect of dietary acid load on bone metabolism during spaceflight., Design: Controlled 4-d diets with a high or low animal protein-to-potassium (APro:K) ratio (High and Low diets, respectively) were given to 17 astronauts before and during spaceflight. Each astronaut had 1 High and 1 Low diet session before flight and 2 High and 2 Low sessions during flight, in addition to a 4-d session around flight day 30 (FD30), when crew members were to consume their typical in-flight intake. At the end of each session, blood and urine samples were collected. Calcium, total protein, energy, and sodium were maintained in each crew member's preflight and in-flight controlled diets., Results: Relative to preflight values, N-telopeptide (NTX) and urinary calcium were higher during flight, and bone-specific alkaline phosphatase (BSAP) was higher toward the end of flight. The High and Low diets did not affect NTX, BSAP, or urinary calcium. Dietary sulfur and age were significantly associated with changes in NTX. Dietary sodium and flight day were significantly associated with urinary calcium during flight. The net endogenous acid production (NEAP) estimated from the typical dietary intake at FD30 was associated with loss of bone mineral content in the lumbar spine after the mission. The results were compared with data from a 70-d bed rest study, in which control (but not exercising) subjects' APro:K was associated with higher NTX during bed rest., Conclusions: Long-term lowering of NEAP by increasing vegetable and fruit intake may protect against changes in loss of bone mineral content during spaceflight when adequate calcium is consumed, particularly if resistive exercise is not being performed. This trial was registered at clinicaltrials.gov as NCT01713634.

Background: Zinc and copper have many physiologic functions and little or no functional storage capability, so persistent losses of either element present health concerns, especially during extended-duration space missions. Objectives: We evaluated the effects of short-term bed rest (BR), a spaceflight analog, on copper and zinc metabolism to better understand the role of these nutrients in human adaptation to (simulated) spaceflight. We also investigated the effect of artificial gravity on copper and zinc homeostasis. Methods: Zinc and copper balances were studied in 15 men [mean ± SD age: 29 ± 3 y; body mass index (in kg/m 2 ): 26.4 ± 2.2] before, during, and after 21 d of head-down tilt BR, during which 8 of the participants were subjected to artificial gravity (AG) by centrifugation for 1 h/d. Control subjects were transferred onto the centrifuge but were not exposed to centrifugation. The study was conducted in a metabolic ward; all urine and feces were collected. Data were analyzed by 2-factor repeated-measures ANOVA. Results: Urinary zinc excretion values for control and AG groups were 33% and 14%, respectively, higher during BR than before BR, and fecal zinc excretion values for control and AG groups were 36% and 19%, respectively, higher during BR, resulting in 67% and 82% lower net zinc balances for controls and AG, respectively (both P < 0.01), despite lower nutrient intake during BR. Fecal copper values for control and AG groups were 40% and 33%, respectively, higher during BR than before BR ( P < 0.01 for both). Urinary copper did not change during BR, but a 19% increase was observed after BR compared with before BR in the AG group ( P < 0.05). Conclusions: The increased fecal excretion of copper and zinc by men during BR suggests that their absorption of these minerals from the diet was reduced, secondary to the release of minerals from bone and muscle. These findings highlight the importance of determining dietary requirements for astronauts on space missions and ensuring provision and intake of all nutrients., Competing Interests: 2: Author disclosures: HN Heacox, PL Gillman, SR Zwart, and SM Smith, no conflicts of interest., (© 2017 American Society for Nutrition.)

Neutral buoyancy's value was far from obvious when human spaceflight began in 1961. Starting in 1964, Environmental Research Associates, a tiny company in the suburbs of Baltimore, developed the key innovations in an obscure research project funded by NASA's Langley Research Center. The new Houston center dismissed it until a mid-1966 EVA crisis, after which it rapidly took over. In parallel, NASA Marshall Space Flight Center developed many of the same techniques, as did many large aerospace corporations, yet the long-run technological impact of corporate activity was near zero. Because ERA and Marshall's pioneering activities led to the two long-running NASA training centers at Houston and Huntsville, those two organizations deserve primary credit for the construction of the neutral buoyancy technological system., (Published by Elsevier Ltd.)

Astronaut intestinal health may be impacted by microgravity, radiation, and diet. The aim of this study was to characterize how high and low linear energy transfer (LET) radiation, microgravity, and elevated dietary iron affect colon microbiota (determined by 16S rDNA pyrosequencing) and colon function. Three independent experiments were conducted to achieve these goals: 1) fractionated low LET γ radiation (137Cs, 3 Gy, RAD), high Fe diet (IRON) (650 mg/kg diet), and a combination of low LET γ radiation and high Fe diet (IRON+RAD) in male Sprague-Dawley rats; 2) high LET 38Si particle exposure (0.050 Gy), 1/6 G partial weight bearing (PWB), and a combination of high LET38Si particle exposure and PWB in female BalbC/ByJ mice; and 3) 13 d spaceflight in female C57BL/6 mice. Low LET radiation, IRON and spaceflight increased Bacteroidetes and decreased Firmicutes. RAD and IRON+RAD increased Lactobacillales and lowered Clostridiales compared to the control (CON) and IRON treatments. Low LET radiation, IRON, and spaceflight did not significantly affect diversity or richness, or elevate pathogenic genera. Spaceflight increased Clostridiales and decreased Lactobacillales, and similar trends were observed in the experiment using a ground-based model of microgravity, suggesting altered gravity may affect colonic microbiota. Although we noted no differences in colon epithelial injury or inflammation, spaceflight elevated TGFβ gene expression. Microbiota and mucosal characterization in these models is a first step in understanding the impact of the space environment on intestinal health.

Bone loss, a key concern for long-duration space travelers, is typically considered a female issue. The number of women who have flown long-duration space missions is now great enough to allow a quantitative comparison of changes in bone and renal stone risk by sex. Participants were 42 astronauts (33 men and 9 women) on long-duration missions to the International Space Station. Bone mineral density (by dual-energy X-ray absorptiometry) and biochemical markers of bone metabolism (from blood and urine samples) were evaluated before and after flight. Data were analyzed in two groups, based on available resistance exercise equipment. Missions were 49 to 215 days in duration, flown between 2000 and 2012. The bone density response to spaceflight was the same for men and women in both exercise groups. The bone mineral density response to flight was the same for men and women, and the typical decrease in bone mineral density (whole body and/or regional) after flight was not observed for either sex for those using an advanced resistive exercise device. Biochemical markers of bone formation and resorption responded similarly in male and female astronauts. The response of urinary supersaturation risk to spaceflight was not significantly different between men and women, although risks were typically increased after flight in both groups, and risks were greater in men than in women before and after flight. The responses of men and women to spaceflight with respect to these measures of bone health were not different., (© 2014 American Society for Bone and Mineral Research.)

Calcium and bone metabolism remain key concerns for space travelers, and ground-based models of space flight have provided a vast literature to complement the smaller set of reports from flight studies. Increased bone resorption and largely unchanged bone formation result in the loss of calcium and bone mineral during space flight, which alters the endocrine regulation of calcium metabolism. Physical, pharmacologic, and nutritional means have been used to counteract these changes. In 2012, heavy resistance exercise plus good nutritional and vitamin D status were demonstrated to reduce loss of bone mineral density on long-duration International Space Station missions. Uncertainty continues to exist, however, as to whether the bone is as strong after flight as it was before flight and whether nutritional and exercise prescriptions can be optimized during space flight. Findings from these studies not only will help future space explorers but also will broaden our understanding of the regulation of bone and calcium homeostasis on Earth.

Astronauts on a mission to Mars would be exposed for up to 3 years to galactic cosmic rays (GCR)--made up of high-energy protons and high charge (Z) and energy (E) (HZE) nuclei. GCR exposure rate increases about three times as spacecraft venture out of Earth orbit into deep space where protection of the Earth's magnetosphere and solid body are lost. NASA's radiation standard limits astronaut exposures to a 3% risk of exposure induced death (REID) at the upper 95% confidence interval (CI) of the risk estimate. Fatal cancer risk has been considered the dominant risk for GCR, however recent epidemiological analysis of radiation risks for circulatory diseases allow for predictions of REID for circulatory diseases to be included with cancer risk predictions for space missions. Using NASA's models of risks and uncertainties, we predicted that central estimates for radiation induced mortality and morbidity could exceed 5% and 10% with upper 95% CI near 10% and 20%, respectively for a Mars mission. Additional risks to the central nervous system (CNS) and qualitative differences in the biological effects of GCR compared to terrestrial radiation may significantly increase these estimates, and will require new knowledge to evaluate.

The United States has had human space flight programs for >50 y and has had a continued presence in space since 2000. Providing nutritious and safe food is imperative for astronauts because space travelers are totally dependent on launched food. Space flight research topics have included energy, protein, nutritional aspects of bone and muscle health, and vision issues related to 1-carbon metabolism. Research has shown that energy needs during flight are similar to energy needs on Earth. Low energy intakes affect protein turnover. The type of dietary protein is also important for bone health, plant-based protein being more efficacious than animal protein. Bone loss is greatly ameliorated with adequate intakes of energy and vitamin D, along with routine resistive exercise. Astronauts with lower plasma folate concentrations may be more susceptible to vision changes. Foods for space flight were developed initially by the U.S. Air Force School of Aerospace Medicine in conjunction with the U.S. Army Natick Laboratories and NASA. Hazard Analysis Critical Control Point safety standards were specifically developed for space feeding. Prepackaged foods for the International Space Station were originally high in sodium (5300 mg/d), but NASA has recently reformulated >90 foods to reduce sodium intake to 3000 mg/d. Food development has improved nutritional quality as well as safety and acceptability.

Bone loss is a well documented phenomenon occurring in humans both in short- and in long-term spaceflights. This phenomenon can be also reproduced on the ground in human and animals and also modeled in cell-based analogs. Since space flights are infrequent and expensive to study the biomedical effects of microgravity on the human body, much of the known pathology of bone loss comes from experimental studies. The most commonly used in vitro simulators of microgravity are clinostats while in vivo simulators include the bed rest studies in humans and hindlimb unloading experiments in animals. Despite the numerous reports that have documented bone loss in wide ranges in multiple crew members, the pathology remains a key concern and development of effective countermeasures is still a major task. Thus far, the offered modalities have not shown much success in preventing or alleviating bone loss in astronauts and cosmonauts. The objective of this review is to capture the most recent research on bone loss from spaceflights, bed rest and hindlimb unloading, and in vitro studies utilizing cellular models in clinostats. Additionally, this review offers projections on where the research has to focus to ensure the most rapid development of effective countermeasures., (Copyright © 2012 Wiley Periodicals, Inc.)

The space flight environment is known to induce bone loss and, subsequently, calcium loss. The longer the mission, generally the more bone and calcium are lost. This review provides a history of bone and calcium studies related to space flight and highlights issues related to calcium excretion that the space program must consider so that urine can be recycled. It also discusses a novel technique using natural stable isotopes of calcium that will be helpful in the future to determine calcium and bone balance during space flight.

Exercise has shown little success in mitigating bone loss from long-duration spaceflight. The first crews of the International Space Station (ISS) used the "interim resistive exercise device" (iRED), which allowed loads of up to 297 lb(f) (or 1337 N) but provided little protection of bone or no greater protection than aerobic exercise. In 2008, the Advanced Resistive Exercise Device (ARED), which allowed absolute loads of up to 600 lb(f) (1675 N), was launched to the ISS. We report dietary intake, bone densitometry, and biochemical markers in 13 crewmembers on ISS missions from 2006 to 2009. Of these 13, 8 had access to the iRED and 5 had access to the ARED. In both groups, bone-specific alkaline phosphatase tended to increase during flight toward the end of the mission (p = 0.06) and increased 30 days after landing (p < 0.001). Most markers of bone resorption were also increased in both groups during flight and 30 days after landing (p < 0.05). Bone densitometry revealed significant interactions (time and exercise device) for pelvis bone mineral density (BMD) and bone mineral content (p < 0.01), hip femoral neck BMD (p < 0.05), trochanter BMD (p < 0.05), and total hip BMD (p < 0.05). These variables were unchanged from preflight only for ARED crewmembers, who also returned from flight with higher percent lean mass and lower percent fat mass. Body mass was unchanged after flight in both groups. All crewmembers had nominal vitamin D status (75 ± 17 nmol/L) before and during flight. These data document that resistance exercise, coupled with adequate energy intake (shown by maintenance of body mass determined by dual-energy X-ray absorptiometry [DXA]) and vitamin D, can maintain bone in most regions during 4- to 6-month missions in microgravity. This is the first evidence that improving nutrition and resistance exercise during spaceflight can attenuate the expected BMD deficits previously observed after prolonged missions., (Copyright © 2012 American Society for Bone and Mineral Research.)

Introduction: Iodine is often used for water purification and has been used throughout the U.S. space program. Because of concern about potential effects on crewmembers' thyroid function, in 1997 a system was implemented on board the Space Shuttles to remove iodine from water before it was consumed. We report here thyroid hormone data from crews flying before and after this system was implemented., Methods: Blood samples were collected and analyzed for thyroid hormone content during routine medical exams before and after Space Shuttle missions. Data are reported for 224 male and 49 female astronauts (about two-thirds of them before implementation of iodine removal)., Results: Serum concentrations of total thyroxine (T4) and the free T4 index were elevated in men after flight and triiodothyronine (T3) was lower after flight, regardless of iodine removal status. T4 was higher, even before flight, in the group of men who flew after iodine removal was implemented. Conversely, T3 was lower in men who flew during that period. Before iodine removal was implemented, thyroid stimulating hormone (TSH) was elevated in male and tended to be elevated in female astronauts, with average increases of 27% and 19% after flight, respectively. After iodine removal was implemented, postflight TSH was not significantly different from preflight values., Discussion: These data provide evidence that crewmembers' increase in serum TSH on landing day after early Shuttle flights resulted from their consumption of iodinated water during spaceflight, because the same increase was not observed after implementation of the iodine removal system.

Introduction: Astronauts exhibit sensorimotor changes upon return from long-duration spaceflight that can result in altered gait kinematics and possibly an increased risk of tripping. Toe trajectory during locomotion is a precise motor control task involving both legs, thus providing a composite metric of locomotor control. The purpose of this study was to determine whether astronauts are at an increased risk of tripping after their return from long-duration spaceflight. This was accomplished by assessing the pre- to postflight changes in toe clearance during treadmill walking., Methods: Ten crewmembers walked on a treadmill while performing a visual-acuity task pre- and postflight., Results: In the three subjects on whom landing day data were available, each exhibited a characteristic of increased tripping risk on landing day: either a decreased median toe clearance or an increased interquartile range (a measure of variance). For all crewmembers, toe clearance median and interquartile range were not significantly different from preflight for the other postflight sessions (the earliest being 1 d after landing). A follow-up analysis showed that changes in foot pitch, ankle dorsiflexion, and pelvis roll angles were significant predictors of changes in toe clearance., Discussion: The landing-day observations indicated an increased risk of tripping, which may pose a hazard during locomotion immediately upon return to Earth, especially in an emergency scenario. However, tripping risk on subsequent days was not different than preflight. The joint angle analysis suggested that the crewmembers tried to reestablish their normal walking pattern postflight, instead of developing a new motor control strategy.

An operationally available diagnostic imaging capability augments spaceflight medical support by facilitating the diagnosis, monitoring and treatment of medical or surgical conditions, by improving medical outcomes and, thereby, by lowering medical mission impacts and the probability of crew evacuation due to medical causes. Microgravity-related physiological changes occurring during spaceflight can affect the genitourinary system and potentially cause conditions such as urinary retention or nephrolithiasis for which ultrasonography (U/S) would be a useful diagnostic tool. This study describes the first genitourinary ultrasound examination conducted in space, and evaluates image quality, frame rate, resolution requirements, real-time remote guidance of nonphysician crew medical officers and evaluation of on-orbit tools that can augment image acquisition. A nonphysician crew medical officer (CMO) astronaut, with minimal training in U/S, performed a self-examination of the genitourinary system onboard the International Space Station, using a Philips/ATL Model HDI-5000 ultrasound imaging unit located in the International Space Station Human Research Facility. The CMO was remotely guided by voice commands from experienced, earth-based sonographers stationed in Mission Control Center in Houston. The crewmember, with guidance, was able to acquire all of the target images. Real-time and still U/S images received at Mission Control Center in Houston were of sufficient quality for the images to be diagnostic for multiple potential genitourinary applications. Microgravity-based ultrasound imaging can provide diagnostic quality images of the retroperitoneum and pelvis, offering improved diagnosis and treatment for onboard medical contingencies. Successful completion of complex sonographic examinations can be obtained even with minimally trained nonphysician ultrasound operators, with the assistance of ground-based real-time guidance.

Spaceflight-induced microgravity appears to be a risk factor for the development of urinary calculi, resulting in urolithiasis during and after spaceflight. Calcifying nanoparticles, or nanobacteria, multiply more rapidly in simulated microgravity and create external shells of calcium phosphate. The question arises whether calcifying nanoparticles are nidi for calculi and contribute to the development of clinically significant urolithiasis in those who are predisposed to the development of urinary calculi because of intrinsic or extrinsic factors. This case report describes a calculus recovered after flight from an astronaut that, on morphologic and immunochemical analysis (including specific monoclonal antibody staining), demonstrated characteristics of calcifying nanoparticles.

The atmosphere of Mars significantly attenuates the heavy ion component of the primary galactic cosmic rays (GCR), however, increases the fluence of secondary light ions (neutrons, and hydrogen and helium isotopes) because of particle production processes. We describe results of the quantum multiple scattering fragmentation (QMSFRG) model for the production of light nuclei through the distinct mechanisms of nuclear abrasion and ablation, coalescence, and cluster knockout. The QMSFRG model is shown to be in excellent agreement with available experimental data for nuclear fragmentation cross sections. We use the QMSFRG model and the space radiation transport code, HZETRN to make predictions of the light particle environment on the Martian surface at solar minimum and near maximum. The radiation assessment detector (RAD) experiment will be launched in 2009 as part of the Mars Science Laboratory (MSL). We make predictions of the expected results for time dependent count-rates to be observed by the RAD experiment. Finally, we consider sensitivity assessments of the impact of the Martian atmospheric composition on particle fluxes at the surface.

Space programmes are shifting toward planetary exploration, and in particular towards missions by human beings to the moon and Mars. However, exposure to space radiation is an important barrier to exploration of the solar system by human beings because of the biological effects of high-energy heavy ions. These ions have a high charge and energy, are the main contributors to radiation risk in deep space, and their biological effects are understood poorly. Predictions of the nature and magnitude of risks posed by exposure to radiation in space are subject to many uncertainties. In recent years, worldwide efforts have focussed on an increased understanding of the oncogenic potential of galactic cosmic rays. A review of the new results in this specialty will be presented here.

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.

Defining optimal nutrient requirements is critical for ensuring crew health during long-duration space exploration missions. Data pertaining to such nutrient requirements are extremely limited. The primary goal of this study was to better understand nutritional changes that occur during long-duration space flight. We examined body composition, bone metabolism, hematology, general blood chemistry, and blood levels of selected vitamins and minerals in 11 astronauts before and after long-duration (128-195 d) space flight aboard the International Space Station. Dietary intake and limited biochemical measures were assessed during flight. Crew members consumed a mean of 80% of their recommended energy intake, and on landing day their body weight was less (P = 0.051) than before flight. Hematocrit, serum iron, ferritin saturation, and transferrin were decreased and serum ferritin was increased after flight (P < 0.05). The finding that other acute-phase proteins were unchanged after flight suggests that the changes in iron metabolism are not likely to be solely a result of an inflammatory response. Urinary 8-hydroxy-2'-deoxyguanosine concentration was greater and RBC superoxide dismutase was less after flight (P < 0.05), indicating increased oxidative damage. Despite vitamin D supplement use during flight, serum 25-hydroxycholecalciferol was decreased after flight (P < 0.01). Bone resorption was increased after flight, as indicated by several markers. Bone formation, assessed by several markers, did not consistently rise 1 d after landing. These data provide evidence that bone loss, compromised vitamin D status, and oxidative damage are among critical nutritional concerns for long-duration space travelers.

Methods used to project risks in low-Earth orbit are of questionable merit for exploration missions because of the limited radiobiology data and knowledge of galactic cosmic ray (GCR) heavy ions, which causes estimates of the risk of late effects to be highly uncertain. Risk projections involve a product of many biological and physical factors, each of which has a differential range of uncertainty due to lack of data and knowledge. Using the linear-additivity model for radiation risks, we use Monte-Carlo sampling from subjective uncertainty distributions in each factor to obtain an estimate of the overall uncertainty in risk projections. The resulting methodology is applied to several human space exploration mission scenarios including a deep space outpost and Mars missions of duration of 360, 660, and 1000 days. The major results are the quantification of the uncertainties in current risk estimates, the identification of factors that dominate risk projection uncertainties, and the development of a method to quantify candidate approaches to reduce uncertainties or mitigate risks. The large uncertainties in GCR risk projections lead to probability distributions of risk that mask any potential risk reduction using the "optimization" of shielding materials or configurations. In contrast, the design of shielding optimization approaches for solar particle events and trapped protons can be made at this time and promising technologies can be shown to have merit using our approach. The methods used also make it possible to express risk management objectives in terms of quantitative metrics, e.g., the number of days in space without exceeding a given risk level within well-defined confidence limits., (Published by Elsevier Ltd on behalf of COSPAR.)

Fluid and energy metabolism and related endocrine changes have been studied nearly from the beginning of human space flight in association with short- and long-duration flights. Fluid and electrolyte nutrition status is affected by many factors including the microgravity environment, stress, changes in body composition, diet, exercise habits, sleep cycles, and ambient temperature and humidity conditions. Space flight exposes astronauts to all these factors and consequently poses significant challenges to establishing dietary water, sodium, potassium, and energy recommendations. The purpose of this article is to review the results of ground-based and space flight research studies that have led to current water, electrolyte, and energy dietary requirements for humans during space flight and to give an overview of related endocrinologic changes that have been observed in humans during short- and long-duration space flight.

Major accomplishments in nutritional sciences for support of human space travel have occurred over the past 40 y. This article reviews these accomplishments, beginning with the early Gemini program and continuing through the impressive results from the first space station Skylab program that focused on life sciences research, the Russian contributions through the Mir space station, the US Shuttle life sciences research, and the emerging International Space Station missions. Nutrition is affected by environmental conditions such as radiation, temperature, and atmospheric pressures, and these are reviewed. Nutrition with respect to space flight is closely interconnected with other life sciences research disciplines including the study of hematology, immunology, as well as neurosensory, cardiovascular, gastrointestinal, circadian rhythms, and musculoskeletal physiology. These relationships are reviewed in reference to the overall history of nutritional science in human space flight. Cumulative nutritional research over the past four decades has resulted in the current nutritional requirements for astronauts. Space-flight nutritional recommendations are presented along with the critical path road map that outlines the research needed for future development of nutritional requirements.

There is considerable interest in developing silicon-based telescopes because of their compactness and low power requirements. Three such telescopes have been flown on board the Space Shuttle to measure the linear energy transfer spectra of trapped, galactic cosmic ray, and solar energetic particles. Dosimeters based on single silicon detectors have also been flown on the Mir orbital station. A comparison of the absorbed dose and radiation quality factors calculated from these telescopes with that estimated from measurements made with a tissue equivalent proportional counter show differences which need to be fully understood if these telescopes are to be used for astronaut radiation risk assessments. Instrument performance is complicated by a variety of factors. A Monte Carlo-based technique was developed to model the behavior of both single element detectors in a proton beam, and the performance of a two-element, wide-angle telescope, in the trapped belt proton field inside the Space Shuttle. The technique is based on: (1) radiation transport intranuclear-evaporation model that takes into account the charge and angular distribution of target fragments, (2) Landau-Vavilov distribution of energy deposition allowing for electron escape, (3) true detector geometry of the telescope, (4) coincidence and discriminator settings, (5) spacecraft shielding geometry, and (6) the external space radiation environment, including albedo protons. The value of such detailed modeling and its implications in astronaut risk assessment is addressed., (c2001 Elsevier Science B.V. All rights reserved.)

A very high-momentum resolution particle spectrometer called the Alpha Magnetic Spectrometer (AMS) was flown in the payload bay of the Space Shuttle in a 51.65 degrees x 380-km orbit during the last solar minimum. This spectrometer has provided the first high statistics data set for galactic cosmic radiation protons, and helium, as well as limited spectral data on carbon and oxygen nuclei in the International Space Station orbit. First measurements of the albedo protons at this inclination were also made. Because of the high-momentum resolution and high statistics, the data can be separated as a function of magnetic latitude. A related investigation, the balloon borne experiment with a superconducting solenoid spectrometer (BESS), has been flown from Lynn Lake, Canada and has also provided excellent high-resolution data on protons and helium. These two data sets have been used here to study the validity of two galactic cosmic ray models and the geomagnetic transmission function developed from the 1990 geomagnetic reference field model. The predictions of both the CREME96 and NASA/JSC models are in good agreement with the AMS data. The shape of the AMS measured albedo proton spectrum, up to 2 GeV, is in excellent agreement with the previous balloon and satellite observations. A new LIS spectrum was developed that is consistent with both previous and new BESS 3He observations. Because the astronaut radiation exposures onboard ISS will be highest around the time of the solar minimum, these AMS measurements and these models provide important benchmarks for future radiation studies. AMS-02 slated for launch in September 2003, will provide even better momentum resolution and higher statistics data., (Published by Elsevier Science Ltd.)

The radiation environment inside a shielded volume is highly complex, consisting of both charged and neutral particles. Since the inception of human space flights, the charged particle component has received virtually all of the attention. There is however, a significant production of secondary neutrons, particularly from the aluminum structure in low earth orbiting spacecrafts. The interactions of galactic cosmic rays (GCR), and solar energetic particles with the earth's atmosphere produce a non-isotropic distribution of albedo neutrons. Inside any reasonable habitable module, the average radiation quality factor of neutrons is about 4-5 times larger than the corresponding average quality factor of charged particles. The measurement of neutrons and their energy spectra is a difficult problem due the intense sources of charged particles. This paper reviews the results of Shuttle flight experiments (made during both solar maximum and solar minimum) to measure the contribution of neutrons to the dose equivalent, as well as theoretical calculations to estimate the appropriate range of neutron energies that contribute most to the dose equivalent., (Published by Elsevier Science Ltd.)

In estimating the crew exposures during an extra vehicular activity (EVA), the contribution of reentrant electrons has always been neglected. Although the flux of these electrons is small compared to the flux of trapped electrons, their energy spectrum extends to several GeV compared to about 7 MeV for trapped electrons. This is also true of splash electrons. Using the measured reentrant electron energy spectra, it is shown that the dose contribution of these electrons to the blood forming organs (BFO) is more that 10 times greater than that from the trapped electrons. The calculations also show that the dose-depth response is a very slowly changing function of depth, and thus adding reasonable amounts of additional shielding would not significantly lower the dose to BFO., (Published by Elsevier Science Ltd.)

The loss of bone during spaceflight is considered a physiological obstacle for the exploration of other planets. This report of calcium metabolism before, during, and after long-duration spaceflight extends results from Skylab missions in the 1970s. Biochemical and endocrine indexes of calcium and bone metabolism were measured together with calcium absorption, excretion, and bone turnover using stable isotopes. Studies were conducted before, during, and after flight in three male subjects. Subjects varied in physical activity, yet all lost weight during flight. During flight, calcium intake and absorption decreased up to 50%, urinary calcium excretion increased up to 50%, and bone resorption (determined by kinetics or bone markers) increased by over 50%. Osteocalcin and bone-specific alkaline phosphatase, markers of bone formation, increased after flight. Subjects lost approximately 250 mg bone calcium per day during flight and regained bone calcium at a slower rate of approximately 100 mg/day for up to 3 mo after landing. Further studies are required to determine the time course of changes in calcium homeostasis during flight to develop and assess countermeasures against flight-induced bone loss.

An episode of nonsustained ventricular tachycardia was recorded from a crew member during the second month aboard the MIR space station. Although asymptomatic, this cardiac event increases the concern that serious cardiac dysrhythmias may be a limiting factor during long-duration spaceflight.

Objective: To develop techniques for conducting a physical examination in microgravity and to describe and document the physiologic changes noted with use of a modified basic physical examination., Design: On the basis of data gathered from physical examinations on KC-135 flights, three physical variables were assessed serially in astronauts during two shuttle missions (of 8- and 10-day duration, respectively). Preflight, in-flight, and postflight examinations were conducted by trained physician-astronauts or flight surgeons, who used this modified examination., Material and Methods: Five male and two female crewmembers participated in the "hands-on" physical examination of all physiologic systems except the genitourinary system. Level of edema, intensity of bowel sounds, and peripheral reflexes were assessed and graded., Results: This investigation identified unique elements of a physical examination performed during space flight that will assist in the development of standard methods for conducting examinations of astronauts in weightlessness. In addition, demonstrable changes induced by microgravity were noted in most physiologic systems examined., Conclusion: The data support the hypothesis that the microgravity examination differs from that conducted on earth or in a 1g environment. In addition, alterations in the physiologic response can be detected with use of hands-on technique. These data are invaluable in the development of optimal medical care for humans in space.

The Space Shuttle has a once-through water system that is initially filled on the ground, partially drained before launch and then refilled with fuel-cell generated water on orbit. The microbiological standard for the Space Shuttle potable water system during this study period allowed only 1 microbe of any kind per l00mL and no detectable coliforms. Contamination episodes in more than 15 years of Shuttle operation have been rare; however, for the past 24 missions, bacterial contamination has been detected in 33% of the samples collected 3d before launch. These samples have had on average 55CFU/100mL of bacteria, with the median less than 1CFU/100mL. Burkholderia cepacia has been the primary contaminant of the Shuttle water supply system both before and after flight. Water samples assessed during the STS-70 mission aboard the Space Shuttle Discovery were found to be contaminated (<20CFU/100mL) with B. cepacia and B. pickettii. In 1991, waste and water lines were removed from the Space Shuttle Columbia and the waste lines were found to harbor biofilms containing Bacillus spp. Nevertheless, the water systems of the four Space Shuttle vehicles provide extremely pure water.

We conducted an opinion survey to improve the characterization of medical risk during spaceflight, using a questionnaire designed to elicit space medicine experts' perceptions of the probability, health effect, and mission impact of selected medical events occurring during spaceflight missions of 30-90 d. This questionnaire was directed toward those events about which little data currently exist, therefore medical events that have occurred during spaceflights with some frequency, such as space motion sickness, were excluded from the questionnaire. The questionnaire was mailed to 99 clinical and research professionals involved with NASA medical programs; 65 responses were returned, of which 60 could be analyzed. The experts rated skin disorders as the most likely to occur, but which would have little effect on mission completion or astronaut health. Circulatory diseases were rated as having the lowest probability of occurrence, but the highest effect on the mission or on a crewmember's health. The results of this survey will be combined with data from analogous populations and existing astronaut health data to establish a data set to support decisions about allocation of health care resources.

Variations in the Earth's trapped (Van Allen) belts produced by solar flare particle events are not well understood. Few observations of increases in particle populations have been reported. This is particularly true for effects in low Earth orbit, where manned spaceflights are conducted. This paper reports the existence of a second proton belt and it's subsequent decay as measured by a tissue-equivalent proportional counter and a particle spectrometer on five Space Shuttle flights covering an eighteen-month period. The creation of this second belt is attributed to the injection of particles from a solar particle event which occurred at 2246 UT, March 22, 1991. Comparisons with observations onboard the Russian Mir space station and other unmanned satellites are made. Shuttle measurements and data from other spacecraft are used to determine that the e-folding time of the peak of the second proton belt. It was ten months. Proton populations in the second belt returned to values of quiescent times within eighteen months. The increase in absorbed dose attributed to protons in the second belt was approximately 20%. Passive dosimeter measurements were in good agreement with this value.

Preparing astronauts to perform the many complex extravehicular activity (EVA) tasks required to assemble and maintain Space Station will be accomplished through training simulations in a variety of facilities. The adequacy of this training is dependent on a thorough understanding of the task to be performed, the environment in which the task will be performed, high-fidelity training hardware and an awareness of the limitations of each particular training facility. Designing hardware that can be successfully operated, or assembled, by EVA astronauts in an efficient manner, requires an acute understanding of human factors and the capabilities and limitations of the space-suited astronaut. Additionally, the significant effect the microgravity environment has on the crew members' capabilities has to be carefully considered not only for each particular task, but also for all the overhead related to the task and the general overhead associated with EVA. This paper will describe various training methods and facilities that will be used to train EVA astronauts for Space Station assembly and maintenance. User-friendly EVA hardware design considerations and recent EVA flight experience will also be presented.

Human exploration of the solar system will include missions lasting years at a time. Such missions mandate extensive regeneration of life support consumables with efficient utilization of local planetary resources. As mission durations extend beyond one or two years, regenerable human life support systems which supply food and recycle air, water, and wastes become feasible; resupply of large volumes and masses of food, water, and atmospheric gases become unrealistic. Additionally, reduced dependency on resupply or self sufficiency can be an added benefit to human crews in hostile environments far from the security of Earth. Comparisons of resupply and regeneration will be discussed along with possible scenarios for developing and implementing human life support systems on the Moon and Mars.

Time-resolved radiation exposure measurements inside the crew compartment have been made during recent Shuttle missions with the USAF Radiation Monitoring Equipment-III (RME-III), a portable four-channel tissue equivalent proportional counter. Results from the first six missions are presented and discussed. The missions had orbital inclinations ranging from 28.5 degrees to 57 degrees, and altitudes from 200-600 km. Dose equivalent rates ranged from 40-5300 micro Sv/dy. The RME-III measurements are in good agreement with other dosimetry measurements made aboard the vehicle. Measurements indicate that medium- and high-LET particles contribute less than 2% of the particle fluence for all missions, but up to 50% of the dose equivalent, depending on the spacecraft's altitude and orbital inclination. Iso-dose rate contours have been developed from measurements made during the STS-28 mission. The drift rate of the South Atlantic Anomaly (SAA) is estimated to be 0.49 degrees W/yr and 0.12 degrees N/yr. The calculated trapped proton and Galactic Cosmic Radiation (GCR) dose for the STS-28 mission were significantly lower than the measured values.

Treatment strategies for Space Motion Sickness (SMS) were compared using the results of postflight oral debriefings. Standardized questionnaires were administered to all crewmembers immediately following Space Shuttle flights by NASA flight surgeons. Cases of SMS were graded as mild, moderate, or severe based on published criteria, and medication effectiveness was judged based on subjective reports of symptom relief. Since October 1989, medication effectiveness is reported inflight through Private Medical Conferences with the crew. A symptom matrix was analyzed for 19 crewmembers treated with oral combination of scopolamine and dextroamphetamine (scopdex) and 15 crewmembers treated with promethazine delivered by intramuscular i.m. or suppository routes. Scopdex has been given preflight as prophylaxis for SMS, but analysis showed delayed symptom presentation in 9 crewmembers or failed to prevent symptoms in 7. Only 3 crewmembers who took scopdex had no symptoms inflight. Fourteen out of 15 crewmembers treated with i.m. promethazine and 6 of 8 treated with promethazine suppositories after symptom development had immediate (within 1-2 h) symptom relief and required no additional medication. There were no cases of delayed symptom presentation in the crewmembers treated with promethazine. This response is in contrast to untreated crewmembers who typically have slow symptom resolution over 72-96 h. We conclude that promethazine is an effective treatment of SMS symptoms inflight. NASA policy currently recommends treating crewmembers with SMS after symptom development, and no longer recommends prophylaxis with scopdex due to delayed symptom development and apparent variable absorption of oral medications during early flight days.

Intramuscular promethazine and its efficacy in the treatment of Space Motion Sickness (SMS) were evaluated using standardized questions administered during postflight debriefings to crewmembers immediately after their first Shuttle flight. Space Motion Sickness was graded as none, mild, moderate, or severe, based on published criteria. Immediate symptom relief (within 1-2 h) was evaluated by subjective reports; medication efficacy was based on scores derived from the four most frequently reported symptoms of SMS: nausea, vomiting, loss of appetite, and stomach awareness. Scores were given for each symptom, mild = 1, moderate = 2, and severe = 3, and added for a total score for each flight day. Following intramuscular (IM) promethazine on flight day 1, the scores were used to determine if the crewmembers were "sick" or "not sick" on flight day 2. On the basis of the scoring criteria, any subject with a score adding to greater than three, with any severe symptom, or with vomiting was defined as "sick." The comparison showed that 25% of crewmembers treated with IM promethazine were "sick" on flight day 2, compared to 50% of crewmembers who did not receive promethazine (p = 0.046). Of crewmembers treated with IM promethazine, 90% reported immediate symptom relief as well. Untreated crewmembers typically have slow symptom resolution over 72-96 h, and those treated with oral scopolamine/dextroamphetamine show delayed symptom development. This study suggests that intramuscular promethazine is an effective treatment for SMS and merits continued use and further controlled investigations.

Treatment strategies for Space Motion Sickness were compared using the results of postflight oral debriefings. Standardized questionnaires were administered to all crewmembers immediately following Space Shuttle flights by NASA flight surgeons. Cases of Space Motion Sickness were graded as mild, moderate or severe based on published criteria, and medication effectiveness was judged based on subjective reports of symptom relief. Since October 1989, medication effectiveness is reported inflight through Private Medical Conferences with the crew. A symptom matrix was analyzed for 19 crewmembers treated with an oral combination of scopolamine and dextroamphetamine (scopdex) and 15 crewmembers treated with promethazine delivered by intramuscular (IM) or suppository routes. Scopdex has been given preflight as prophaxis for Space Motion Sickness but analysis showed delayed symptom presentation in 9 crewmembers or failed to prevent symptoms in 7. Only three crewmembers who took scopdex had no symptoms inflight. Fourteen out of 15 crewmembers treated with IM promethazine and 6 of 8 treated with promethazine suppositories after symptom development had immediate (within 12 h) symptom relief and required no additional medication. There were no cases of delayed symptom presentation in the crewmembers treated with promethazine. This response is in contrast to untreated crewmembers who typically have slow symptom resolution over 72-96 h. We conclude that promethazine is an effective treatment of Space Motion Sickness symptoms inflight. NASA policy currently recommends treating crewmembers with Space Motion Sickness after symptom development, and no longer recommends prophylaxis with scopdex due to delayed symptom development and apparent variable absorption of oral medications during early flight days.

The effects of space flight on the cardiovascular system have been studied since the first manned flights. In several instances, the results from these investigations have directly contradicted the predictions based on established models. Results suggest associations between space flight's effects on other organ systems and those on the cardiovascular system. Such findings provide new insights into normal human physiology. They must also be considered when planning for the safety and efficiency of space flight crewmembers.

Crewmembers on missions to the Moon or Mars will be unavoidably exposed to ionizing radiation as they pass through the Van Allen belts and the Galactic Cosmic Ray (GCR) flux. There is the possibility for exposure to proton radiation from Solar Particle Events (SPE). Using absorbed doses and ICRP 26, Linear Energy Transfer (LET) -dependent quality factors, the following dose-equivalents are estimated: In a spacecraft with 0.75 cm aluminum walls (2 g/cm2) at solar minimum, the lunar round trip dose-equivalent is less than 0.05 Sv. During a Mars mission the estimated dose-equivalents are: outbound (Van Allen Belts) <0.02 Sv; Earth to Mars (205 days exposure to free space GCR) 0.32 Sv; 30 days on the Martian surface (GCR) 0.023 Sv; Mars to Earth (225 days exposure to free space) 0.35 Sv; and through the Van Allen Belts 0.02 Sv. Conventionally, the total of 0.73 Sv over 460 days could be expected to increase the risk of cancer mortality in a 35-year old male astronaut by about one percent. However three-fourths of the dose-equivalent in free space is contributed by high LET heavy ions (Z > or = 3) and target fragments with average quality factors of 10.3 and 20 respectively. The biological effectiveness of these radiations is poorly understood; so the quality factors are set at conservatively very high values. The entire concept of absorbed dose/quality factor/dose-equivalent as applied to GCR must be reconsidered.

The purpose of this report is to provide an introduction and overview of the Skylab medical program. Some of the more important medical systems and equipment provided for crew sustenance are described. The major inflight medical experiments are reviewed, and the test programs are discussed. The medical operations procedures and the techniques used to monitor crew health are reviewed to provide an understanding of the medical management of this complex mission.

In the last 20 years, the biomedical problems facing man in space have been brought into sharper focus. Space motion sickness is presently our most serious problem. Its etiology remains obscure, but the "sensory conflict" theory appears most plausible. No valid predictive tests of susceptibility exist and presently we must rely on medication for prevention or mitigation of symptoms. Adaptation/biofeedback techniques may prove useful. Cardiovascular "deconditioning" may be effectively attenuated by use of anti-g suits or plasma expanding techniques. Recent bedrest simulation studies would seem to indicate that concerns about chronically elevated central venous pressure during space flight are unfounded. The loss of red cell mass in space flight appears to be self-limited, independent of mission duration, and not of clinical concern, based on recent Soviet experiences. And finally, clodronate, a new diphosphonate effective in preventing hypercalciuria and negative calcium balance in normal human bedrested subjects, may prove effective in preventing or lessening skeletal mineral loss in space.

The sleep monitoring experiment permitted an objective evaluation of sleep characteristics during the first two manned Skylab flights. Hardware located onboard the spacecraft accomplished data acquisition, analysis, and preservation, thereby permitting near-real-time evaluation of sleep during the flights and more detailed postmission analysis. The crewman studied during the 28-Day Mission showed some decrease in total sleep time an increase in the percentage of Stage 4 sleep, while the subject in the 59-Day Mission exhibited little change in total sleep time and a small decrease in Stage 4 and REM sleep. Some disruption of sleep characteristics was seen in the final days of both missions, and both subjects exhibited decreases in REM-onset latency in the immediate postflight period. The relatively minor changes seen were not of the type nor magnitude which might be expected to be associated with significant degradation of performance capability.

Data have been accumulated from a series of studies in which men have been subjected to weightlessness in orbital space flight for periods of up to 12 weeks. These data are used to predict the long term consequences of weightlessness upon the skeletal system. Space flight induced a loss of calcium which accelerated exponentially from about 50 mg/d at the end of 1 week to approx. 300 mg/d at the end of 12 weeks. The hypercalciuria reached a constant level within 4 weeks while fecal calcium losses continued to increase throughout the period of exposure. This apparent diminution of gastrointestinal absorptive efficiency was accompanied by a slight decline in the plasma level of parathyroid hormone and a slight elevation in the plasma level of calcium and phosphorus. Although losses in mineral from the calcaneus were closely correlated with the calcium imbalance, no changes were detected in the mineral mass of the ulna and radius. From the data presented it is concluded that the process of demineralization observed in space flight is more severe than would be predicted on the basis of observations in immobilized, bed rested, or paralyzed subjects. It is, moreover, suggested that the process may not be totally reversible.