ALBERT

Description: BACKGROUND: Medical operations on the International Space Station will emphasize the stabilization and transport of critically injured personnel and so will need to be capable of advanced trauma life support (ATLS). METHODS: We evaluated the ATLS invasive procedures in the microgravity environment of parabolic flight using a porcine animal model. Included in the procedures evaluated were artificial ventilation, intravenous infusion, laceration closure, tracheostomy, Foley catheter drainage, chest tube insertion, peritoneal lavage, and the use of telemedicine methods for procedural direction. RESULTS: Artificial ventilation was performed and appeared to be unaltered from the 1-G environment. Intravenous infusion, laceration closure, percutaneous dilational tracheostomy, and Foley catheter drainage were achieved without difficulty. Chest tube insertion and drainage were performed with no more difficulty than in the 1-G environment due to the ability to restrain patient, operator and supplies. A Heimlich valve and Sorenson drainage system were both used to provide for chest tube drainage collection with minimal equipment, without the risk of atmospheric contamination, and with the capability to auto-transfuse blood drained from a hemothorax. The use of telemedicine in chest tube insertion was demonstrated to be useful and feasible. Peritoneal lavage using a percutaneous technique, although requiring less training to perform, was found to be dangerous in weightlessness due to the additional pressure of the bowel on the anterior abdominal wall creating a high risk of bowel perforation. CONCLUSIONS: The performance of ATLS procedures in microgravity appears to be feasible with the exception of diagnostic peritoneal lavage. Minor modifications to equipment and techniques are required in microgravity to effect surgical drainage in the presence of altered fluid dynamics, to prevent atmospheric contamination, and to provide for the restraint requirements. A parabolic simulation system was developed for equipment and procedure verification, physiological research, and possible crew medical officer training in the future.

Description: During two years, from November 1994 to 1996, the particle detector REM measured the highly energetic electron and proton environment at the outside of the MIR orbital station. Using mission averaged data we investigate various aspects of the proton fluxes in the SAA. Comparison with the radiation belt model AP8 reveal important differences. c2002 Elsevier Science Ltd. All rights reserved.

Description: The photosynthetic rate, the leaf characteristics related to photosynthesis, such as the chlorophyll content, chlorophyll a/b ratio and density of the stomata, the leaf area and the dry weight in seedlings of Japanese flowering cherry grown under normal gravity and simulated microgravity conditions were examined. No significant differences were found in the photosynthetic rates between the two conditions. Moreover, leaf characteristics such as the chlorophyll content, chlorophyll a/b ratio and density of the stomata in the seedlings grown under the simulated microgravity condition were not affected. However, the photosynthetic product of the whole seedling under the simulated microgravity condition increased compared with the control due to its leaf area increase. The results suggest that dynamic gravitational stimulus controls the partitioning of the products of photosynthesis.

Description: BACKGROUND: Fiber atrophy and an increase in the percentage of fast fibers have been observed in Rhesus leg muscles after spaceflight. Hypothesis: Hypergravity will result in muscle fiber hypertrophy and an increase in the percentage of slow fibers. METHODS: Open muscle biopsies were obtained from Rhesus soleus, medial gastrocnemius (MG), and tibialis anterior (TA) muscles before and after 14 d of centrifugation (2 G) and in time-matched controls. Cage activity levels were measured by telemetry. RESULTS: Based on monoclonal antibody binding for myosin heavy chains (MHC), the fastest region of soleus contained a higher proportion of type I+II (27 vs. 13%) and had a tendency for a lower proportion of type I (38 vs. 61%, p = 0.10) fibers after than before centrifugation. There was a higher proportion of type I+II fibers in post- vs. pre-2 G (10 vs. 0.6%) MG biopsies. Fiber type distribution and MHC composition were unaffected in the TA. Overall, mean fiber sizes were unaffected by centrifugation. Average cage activity levels were 36% lower during than before 2 G. CONCLUSIONS: Our hypothesis was rejected. The changes in the proportion of fibers expressing type I MHC are the reverse of that expected with chronic loading of extensors and, paradoxically, are similar to changes observed with chronic unloading, such as occurs during spaceflight, in this primate model. The data are consistent with the observed decrease in total daily activity levels.

Description: We investigated the effect of major histocompatibility complex class II (MHC II) knockout on the development of the mouse peripheral skeleton. These C2D mice had less skeletal development at 8, 12 and 16 weeks of age compared to wild-type C57BL/6J (B6) male mice. The C2D mice had decreased femur mechanical, geometric and compositional measurements compared to wild type mice at each of these ages. C2D femur stiffness (S), peak force in 3-pt bending (Pm), and mineral mass (Min-M) were 74%, 64% and 66%, respectively, of corresponding B6 values at 8 weeks of age. Similar differences were measured at 12 weeks (for which C2D femoral S, Pm and Min-M were 71%, 72% and 73%, respectively, of corresponding B6 values) and at 16 weeks (for which C2D femoral S, Pm and Min-M were 80%, 66% and 61%, respectively, of corresponding B6 values). MHC II knockout delays the development of adult bone properties and is accompanied by lower body mass compared to wild-type controls.

Description: The structure of the adult skeleton is determined, in large part, by its genome. Whether genetic variations may influence the effectiveness of interventions to combat skeletal diseases remains unknown. The differential response of trabecular bone to an anabolic (low-level mechanical vibration) and a catabolic (disuse) mechanical stimulus were evaluated in three strains of adult mice. In low bone-mineral-density C57BL/6J mice, the low-level mechanical signal caused significantly larger bone formation rates (BFR) in the proximal tibia, but the removal of functional weight bearing did not significantly alter BFR. In mid-density BALB/cByJ mice, mechanical stimulation also increased BFR, whereas disuse significantly decreased BFR. In contrast, neither anabolic nor catabolic mechanical signals influenced any index of bone formation in high-density C3H/HeJ mice. Together, data from this study indicate that the sensitivity of trabecular tissue to both anabolic and catabolic stimuli is influenced by the genome. Extrapolated to humans, these results may explain in part why prophylaxes for low bone mass are not universally effective, yet also indicate that there may be a genotypic indication of people who are at reduced risk of suffering from bone loss.

Description: Elevated serum levels of insulin-like growth factor binding protein-2 (IGFBP-2) and a precursor form of IGF-II are associated with marked increases in bone formation and skeletal mass in patients with hepatitis C-associated osteosclerosis. In vitro studies indicate that IGF-II in complex with IGFBP-2 has high affinity for bone matrix and is able to stimulate osteoblast proliferation. The purpose of this study was to determine the ability of the IGF-II/IGFBP-2 complex to increase bone mass in vivo. Osteopenia of the femur was induced by unilateral sciatic neurectomy in rats. At the time of surgery, 14-day osmotic minipumps containing vehicle or 2 microg IGF-II+9 microg IGFBP-2/100g body weight/day were implanted subcutaneously in the neck. Bone mineral density (BMD) measurements were taken the day of surgery and 14 days later using a PIXImus small animal densitometer. Neurectomy of the right hindlimb resulted in a 9% decrease in right femur BMD (P〈0.05 vs. baseline). This loss in BMD was completely prevented by treatment with IGF-II/IGFBP-2. On the control limb, there was no loss of BMD over the 14 days and IGF-II/IGFBP-2 treatment resulted in a 9% increase in left femur BMD (P〈0.05). Bone histomorphometry indicated increases in endocortical and cancellous bone formation rates and in trabecular thickness. These results demonstrate that short-term administration of the IGF-II/IGFBP-2 complex can prevent loss of BMD associated with disuse osteoporosis and stimulate bone formation in adult rats. Furthermore, they provide proof of concept for a novel anabolic approach to increasing bone mass in humans with osteoporosis.

Description: BACKGROUND: An objective method that accurately quantifies the severity of Acute Mountain Sickness (AMS) symptoms is needed to enable more reliable evaluation of altitude acclimatization and testing of potentially beneficial interventions. HYPOTHESIS: Changes in human articulation, as quantified by timed variations in acoustic waveforms of specific spoken words (voice onset time; VOT), are correlated with the severity of AMS. METHODS: Fifteen volunteers were exposed to a simulated altitude of 4300 m (446 mm Hg) in a hypobaric chamber for 48 h. Speech motor control was determined from digitally recorded and analyzed timing patterns of 30 different monosyllabic words characterized as voiced and unvoiced, and as labial, alveolar, or velar. The Environmental Symptoms Questionnaire (ESQ) was used to assess AMS. RESULTS: Significant AMS symptoms occurred after 4 h, peaked at 16 h, and returned toward baseline after 48 h. Labial VOTs were shorter after 4 and 39 h of exposure; velar VOTs were altered only after 4 h; and there were no changes in alveolar VOTs. The duration of vowel sounds was increased after 4 h of exposure and returned to normal thereafter. Only 1 of 15 subjects did not increase vowel time after 4 h of exposure. The 39-h labial (p = 0.009) and velar (p = 0.037) voiced-unvoiced timed separations consonants and the symptoms of AMS were significantly correlated. CONCLUSIONS: Two objective measures of speech production were affected by exposure to 4300 m altitude and correlated with AMS severity. Alterations in speech production may represent an objective measure of AMS and central vulnerability to hypoxia.

Description: BACKGROUND: A discrepancy exists between the incidence of ground-based decompression sickness (DCS) during simulated extravehicular activity (EVA) at hypobaric space suit pressure (20-40%) and crewmember reports during actual EVA (zero reports). This could be due to the effect of gravity during ground-based DCS studies. HYPOTHESIS: At EVA suit pressures of 29.6 kPa (4.3 psia), there is no difference in the incidence of hypobaric DCS between a control group and group exposed to simulated weightlessness (supine body position). METHODS: Male subjects were exposed to a hypobaric pressure of 29.6 kPa (4.3 psi) for up to 4 h. The control group (n = 26) pre-oxygenated for 60 min (first 10 min exercising) before hypobaric exposure and walking around in the altitude chamber. The test group (n = 39) remained supine for a 3 h prior to and during the 60-min pre-oxygenation (also including exercise) and at hypobaric pressure. DCS symptoms and venous gas emboli (VGE) at hypobaric pressure were registered. RESULTS: DCS occurred in 42% in the control and in 44% in simulated weightlessness group (n.s.). The mean time for DCS to develop was 112 min (SD +/- 61) and 123 min (+/- 67), respectively. VGE occurred in 81% of the control group subjects and in 51% of the simulated weightlessness subjects (p = 0.02), while severe VGE occurred in 58% and 33%, respectively (p = 0.08). VGE started after 113 min (+/- 43) in the control and after 76 min (+/- 64) in the simulated weightlessness group. CONCLUSIONS: No difference in incidence of DCS was shown between control and simulated weightlessness conditions. VGE occurred more frequently during the control condition with bubble-releasing arm and leg movements.

Description: The purpose of the present study was to examine postprandial myoelectric activity of the stomach and gastric activity associated with space motion sickness using electrogastrography. Three crewmembers participated in this investigation. Preflight, subjects exhibited normal postprandial responses to the ingestion of a meal. Inflight, crewmembers exhibited an abnormal decrease in the power of the normal gastric slow wave after eating on flight day 1, but had a normal postprandial response by flight day 3. Prior to and during episodes of nausea and vomiting, the electrical activity of the stomach became dysrhythmic with 60-80% of the spectral power in the bradygastric and tachygastric frequency ranges. These findings indicate that gastric motility may be decreased during the first few days of space flight. In addition, changes in the frequency of the gastric slow wave associated with space motion sickness symptoms are consistent with those reported for laboratory-induced motion sickness.

Description: PURPOSE: Supine, moderate exercise is ineffective in maintaining orthostatic tolerance after bed rest (BR). Our purpose was to test the hypothesis that adding an orthostatic stress during exercise would maintain orthostatic function after BR. METHODS: Seven healthy men completed duplicate 15-d 6 degrees head-down tilt BR using a crossover design. During one BR, subjects did not exercise (CON). During another BR, subjects exercised for 40 min.d(-1) on a supine treadmill against 50-60 mm Hg LBNP (EX). Exercise training consisted of an interval exercise protocol of 2- to 3-min intervals alternating between 41 and 65% (.)VO(2max). Before and after BR, an LBNP tolerance test was performed in which the LBNP chamber was decompressed in 10-mm Hg stages every 3 min until presyncope. RESULTS: LBNP tolerance, as assessed by the cumulative stress index (CSI) decreased after BR in both the CON (830 +/- 144, pre-BR vs 524 +/- 56 mm Hg.min, post-BR) and the EX (949 +/- 118 pre-BR vs 560 +/- 44 mm Hg.min, post-BR) conditions. However, subtolerance (0 to -50 mm Hg LBNP) heart rates were lower and systolic blood pressures were better maintained after BR in the EX condition compared with CON. CONCLUSION: Moderate exercise performed against LBNP simulating an upright 1-g environment failed to protect orthostatic tolerance after 15 d of BR.

Description: BACKGROUND: The use of centrifugation at 1 G has been advocated as a control condition during spaceflight and as a countermeasure to compensate for the adverse effects of spaceflight. Rodents are the primary animal model for the study of the effects of spaceflight and will be used in the evaluation of centrifugation as a countermeasure and means of control at 1 G during flight. HYPOTHESIS: The present study was designed to assess whether resting energy expenditure (EER) of male rats was increased in relation to the magnitude of the level of gravity to which the animals were exposed. The influence of body mass and age on resting energy expenditure (EER) of male rats (n = 42, age 40-400 d) was determined following 2 wk of acclimation to 1, 2.3, or 4.1 G. Hypergravity environments were created by centrifugation. Measurements were made at the gravity level to which the animal was acclimated and during the lights-on period. RESULTS: In rats matched for body mass (approximately 400 g), mean O2 consumption and CO2 production were higher (18% and 27%, respectively) in the 2.3- and 4.1 -G groups than controls. Mean respiratory exchange ratio (RER) increased from 0.80 to 0.87. EER was increased from 47 +/- 0.1 kcal x d(-1) at 1 G, to 57 +/- 1.5 and 58 +/- 2.2 kcal x d(-1) at 2.3 and 4.1 G, respectively. There was no difference in EER between the hypergravity groups. When age differences were considered, EER (kcal x kg(-1) x d(-1)) with increased gravity was 40% higher than at 1 G. The increase in EER was not proportional over gravity levels. CONCLUSION: Acclimation of rats to hypergravity increases their EER, dependent on body mass and age, and may alter substrate metabolism. The increase in EER was not related to the level of gravity increase.

Description: BACKGROUND: As a medical emergency that can affect even well-screened, healthy individuals, peritonitis developing during a long-duration space exploration mission may dictate deviation from traditional clinical practice due to the absence of otherwise indicated surgical capabilities. Medical management can treat many intra-abdominal processes, but treatment failures are inevitable. In these circumstances, percutaneous aspiration under sonographic guidance could provide a "rescue" strategy. Hypothesis: Sonographically guided percutaneous aspiration of intra-peritoneal fluid can be performed in microgravity. METHODS: Investigations were conducted in the microgravity environment of NASA's KC-135 research aircraft (0 G). The subjects were anesthetized female Yorkshire pigs weighing 50 kg. The procedures were rehearsed in a terrestrial animal lab (1 G). Colored saline (500 mL) was introduced through an intra-peritoneal catheter during flight. A high-definition ultrasound system (HDI-5000, ATL, Bothell, WA) was used to guide a 16-gauge needle into the peritoneal cavity to aspirate fluid. RESULTS: Intra-peritoneal fluid collections were easily identified, distinct from surrounding viscera, and on occasion became more obvious during weightless conditions. Subjectively, with adequate restraint of the subject and operators, the procedure was no more demanding than during the 1-G rehearsals. CONCLUSIONS: Sonographically guided percutaneous aspiration of intra-peritoneal fluid collections is feasible in weightlessness. Treatment of intra-abdominal inflammatory conditions in spaceflight might rely on pharmacological options, backed by sonographically guided percutaneous aspiration for the "rescue" of treatment failures. While this risk mitigation strategy cannot guarantee success, it may be the most practical option given severe resource limitations.

Description: Weightlessness induces bone loss. Understanding the nature of this loss and developing means to counteract it are significant challenges to potential human exploration missions. This article reviews the existing information from studies of bone and calcium metabolism conducted during space flight. It also highlights areas where nutrition may play a specific role in this bone loss, and where countermeasures may be developed to mitigate that loss.

Description: Exercise and nutrition represent primary countermeasures used during space flight to maintain or restore maximal aerobic capacity, musculoskeletal structure, and orthostatic function. However, no single exercise, dietary regimen, or combination of prescriptions has proven entirely effective in maintaining or restoring cardiovascular and musculoskeletal functions to preflight levels after prolonged space flight. As human space flight exposures increase in duration, identification, assessment, and development of various effective exercise- and nutrition-based protective procedures will become paramount. The application of adequate dietary intake in combination with effective exercise prescription will be based on identification of basic physiologic stimuli that maintain normal function in terrestrial gravity, and understanding how specific combinations of exercise characteristics (e.g., duration, frequency, intensity, and mode) can be combined with minimal nutritional requirements that mimic the stimuli normally produced by living in Earth's gravity environment. This can be accomplished only with greater emphasis of research on ground-based experiments targeted at understanding the interactions between caloric intake and expenditure during space flight. Future strategies for application of nutrition and exercise countermeasures for long-duration space missions must be directed to minimizing crew time and the impact on life-support resources.

Description: It is very likely that the human immune system will be altered in astronauts exposed to the conditions of long-term space flight: isolation, containment, microgravity, radiation, microbial contamination, sleep disruption, and insufficient nutrition. In human and animal subjects flown in space, there is evidence of immune compromise, reactivation of latent virus infection, and possible development of a premalignant or malignant condition. Moreover, in ground-based space flight model investigations, there is evidence of immune compromise and reactivation of latent virus infection. All of these observations in space flight itself or in ground-based models of space flight have a strong resonance in a wealth of human pathologic conditions involving the immune system where reactivated virus infections and cancer appear as natural consequences. The clinical conditions of Epstein-Barr-driven lymphomas in transplant patients and Kaposi's sarcoma in patients with autoimmune deficiency virus come easily to mind in trying to identify these conditions. With these thoughts in mind, it is highly appropriate, indeed imperative, that careful investigations of human immunity, infection, and cancer be made by space flight researchers.

Description: Space flight is associated with an increase in oxidative stress after return to 1g. The effect is more pronounced after long-duration space flight. The effects lasts for several weeks after landing. In humans there is increased lipid peroxidation in erythrocyte membranes, reduction in some blood antioxidants, and increased urinary excretion of 8-iso-prostaglandin F(2alpha) and 8-oxo-7,8 dihydro-2 deoxyguanosine. Isoprostane 8-iso-prostaglandin F(2alpha) and 8-oxo-7,8 dihydro-2 deoxyguanosine are markers for oxidative damage to lipids and DNA, respectively. The changes have been attributed to a combination of the energy deficiency that occurs during flight and substrate competition for amino acids occurring between repleting muscle and other tissues during the recovery phase. The observations in humans have been complemented by rodent studies. Most rodent studies showed increased production of lipid peroxidation products postflight and decreased antioxidant enzyme activity postflight. The rodent observations were attributed to the stress associated with reentry into Earth's gravity. Decreasing the imbalance between the production of endogenous oxidant defenses and oxidant production by increasing the supply of dietary antioxidants may lessen the severity of the postflight increase in oxidative stress.

Description: Conducting research during actual or simulated weightlessness is a challenging endeavor, where even the simplest activities may present significant challenges. This article reviews some of the potential obstacles associated with performing research during space flight and offers brief descriptions of current and previous space research platforms and ground-based analogs, including those for human, animal, and cell-based research. This review is intended to highlight the main issues of space flight research analogs and leave the specifics for each physiologic system for the other papers in this section.

Description: Smart medical systems are being developed to allow medical treatments to address alterations in chemical and physiologic status in real time. In a smart medical system, sensor arrays assess subject status, which is interpreted by computer processors that analyze multiple inputs and recommend treatment interventions. The response of the subject to the treatment is again assessed by the sensor arrays, thus closing the loop. An early form of "smart medicine" has been practiced in space to assess nutrition. Nutrient levels are assessed with food frequency questionnaires, which are interpreted by flight surgeons to recommend inflight alterations in diet. In the future, sensor arrays will directly probe body chemistry. Near-infrared spectroscopy can be used to non-invasively measure several blood and tissue parameters that are important in the assessment of nutrition and fitness. In particular, this technology can be used to measure blood hematocrit and interstitial fluid pH. The non-invasive measurement of interstitial pH is discussed as a surrogate for blood lactate measurement for the development and real-time assessment of exercise protocols in space. Earth-based application of these sensors is also described.

Description: The Mir Orbital Station provided a unique platform on which to carry out a variety of space radiation dosimetry measurements. A number of experiments were conducted using a combination of passive detectors on the interior of the Mir during 1996-97. Thermoluminescent detectors were used to measure absorbed dose. CR-39 plastic nuclear track detectors were used to measure the LET spectra 〉 or =5 keV.microm(-1). Results from TLDs and CR-39 PNTDs were combined to determine total dose and dose equivalent. Mean dose rate was found to decrease while mean dose equivalent rate and average quality factor increased with increasing shielding. Secondary particles from proton-induced target fragmentation interactions, not primary HZE particles, were found to be the largest contributor to the LET spectrum above 100 keV.microm(-1). During the 1997 measurements, mean quality factor was found to vary from 1.7 to 2.1 as a function of location within the Mir.

Description: As evidenced from Mir and other long-duration space missions, the space environment can cause significant alterations in the human physiology that could prove dangerous for astronauts. The NASA programme to develop countermeasures for these deleterious human health effects is being carried out by the National Space Biomedical Research Institute (NSBRI). The NSBRI has 12 research teams, ten of which are primarily physiology based, one addresses on-board medical care, and the twelfth focuses on technology development in support of the other research teams. This Technology Development (TD) Team initially supported four instrumentation developments: (1) an advanced, multiple projection, dual energy X ray absorptiometry (AMPDXA) scanning system: (2) a portable neutron spectrometer; (3) a miniature time-of-flight mass spectrometer: and (4) a cardiovascular identification system. Technical highlights of the original projects are presented along with an introduction to the five new TD Team projects being funded by the NSBRI.

Description: Chips of a radiophotoluminescence glass dosemeter (RPLG) were used for measurements of space radiation during a 9.8 d Shuttle-Mir mission (STS-91) at an altitude of 400 km and an inclination of 51.65 degrees. Two of RPLG chips were put into each of 59 positions in or on a life-size human phantom. The RPLG values equivalent to 137Cs gamma ray absorbed doses were found to be systematically lower than those of a Mg2SiO4:Tb thermoluminescence dosemeter (TDMS). In comparison with the organ or tissue absorbed dose and dose equivalent values that were estimated using a combination of TDMS and plastic nuclear track detectors, the efficiencies of the RPLG chips were about 80% for the water absorbed dose and about 40% for the dose equivalent. Whereas the percentage values will change during different missions, such additional information obtained from small RPLG chips is useful for improving the reliability of radiation dosimetry in space.

Description: NASA is contemplating sending humans to Mars and to the moon for further exploration. Volcanic ashes from Arizona and Hawaii with mineral properties similar to those of lunar and Martian soils, respectively, are used to simulate lunar and Martian environments for instrument testing. Martian soil is highly oxidative; this property is not found in Earth's volcanic ashes. NASA is concerned about the health risk from potential exposure of workers in the test facilities. Fine lunar soil simulant (LSS), Martian soil simulant (MSS), titanium dioxide, or quartz in saline was intratracheally instilled into groups of 4 mice (C57BL/6J) at 0.1 mg/mouse (low dose, LD) or 1 mg/mouse (high dose, HD). Separate groups of mice were exposed to ozone (0.5 ppm for 3 h) prior to MSS instillation. Lungs were harvested for histopathological examination 7 or 90 days after the single dust treatment. The lungs of the LSS-LD groups showed no evidence of inflammation, edema, or fibrosis; clumps of particles and an increased number of macrophages were visible after 7 days but not 90 days. In the LSS-HD-7d group, the lungs showed mild to moderate alveolitis, and perivascular and peribronchiolar inflammation. The LSS-HD-90d group showed signs of mild chronic pulmonary inflammation, septal thickening, and some fibrosis. Foci of particle-laden macrophages (PLMs) were still visible. Lung lesions in the MSS-LD-7d group were similar to those observed in the LSS-HD-7d group. The MSS-LD-90d group had PLMs and scattered foci of mild fibrosis in the lungs. The MSS-HD-7d group showed large foci of PLMs, intra-alveolar debris, mild-to-moderate focal alveolitis, and perivascular and peribronchiolar inflammation. The MSS-HD-90d group showed focal chronic mild-to-moderate alveolitis and fibrosis. The findings in the O(3)-MSS-HD-90d group included widespread intra-alveolar debris, focal moderate alveolitis, and fibrosis. Lung lesions in the MSS groups were more severe with the ozone pretreatment. The effects of O(3) and MSS coexposure appeared to be more than additive. Results for the TiO(2) and quartz controls were consistent with the known pulmonary toxicity of these compounds. The overall severity of lung injury was TiO(2) 〈 LSS 〈 MSS 〈 O(3) + MSS 〈 quartz. Except for TiO(2), the increased duration of dust presence in the lung from 7 to 90 days transformed the acute inflammatory response to a chronic inflammatory lesion. This study showed that LSS and MSS are more hazardous in the lungs than nuisance dusts.

Description: Volcanic ashes from Arizona and Hawaii, with chemical and mineral properties similar to those of lunar and Martian soils, respectively, are used by the National Aeronautics and Space Administration (NASA) to simulate lunar and Martian environments for instrument tests. NASA needs toxicity data on these volcanic soils to assess health risks from potential exposures of workers in facilities where these soil simulants are used. In this study we investigated the acute effects of lunar soil simulant (LSS) and Martian soil simulant (MSS), as a complement to a histopathological study assessing their subchronic effects (Lam et al., 2002). Fine dust of LSS, MSS, TiO(2), or quartz suspended in saline was intratracheally instilled into C57Bl/6J mice (4/group) in single doses of 0.1 mg/mouse or 1 mg/mouse. The mice were euthanized 4 or 24 h after the dust treatment, and bronchoalveolar lavage fluid (BALF) was obtained. Statistically significant lower cell viability and higher total protein concentration in the BALF were seen only in mice treated with the high dose of quartz for 4 h and with the high dose of MSS or quartz for 24 h, compared to mice treated only with saline. A significant increase in the percentage of neutrophils was not observed with any dust-treated group at 4 h after the instillation, but was observed after 24 h in all the dust-treated groups. This observation indicates that these dusts were not acutely toxic and the effects were gradual; it took some time for neutrophils to be recruited into and accumulate significantly in the lung. A statistically significant increase in apoptosis of lavaged macrophages from mice 4 h after treatment was found only in the high-dose silica group. The overall results of this study on the acute effects of these dusts in the lung indicate that LSS is slightly more toxic than TiO(2), and that MSS is comparable to quartz. These results were consistent with the subchronic histopathological findings in that the order of severity of lung toxicity was TiO(2) 〈 LSS 〈 MSS 〈 quartz.

Description: INTRODUCTION: Pulmonary altitude decompression sickness (DCS) is a rare condition. 'Chokes' which are characterized by the triad of substernal pain, cough, and dyspnea, are considered to be associated with severe accumulation of gas bubbles in the pulmonary capillaries and may rapidly develop into a life-threatening medical emergency. This study was aimed at characterizing early symptomatology and the appearance of venous gas emboli (VGE). METHODS: Symptoms of simulated-altitude DCS and VGE (with echo-imaging ultrasound) were analyzed in 468 subjects who participated in 22 high altitude hypobaric chamber research protocols from 1983 to 2001 at Brooks Air Force Base, TX. RESULTS: Of 2525 subject-exposures to simulated altitude, 1030 (41%) had symptoms of DCS. Only 29 of those included DCS-related pulmonary symptoms. Of these, only 3 subjects had all three pulmonary symptoms of chokes; 9 subjects had two of the pulmonary symptoms; and 17 subjects had only one. Of the 29 subject-exposures with pulmonary symptoms, 27 had VGE and 21 had severe VGE. The mean onset times of VGE and symptoms in the 29 subject-exposures were 42 +/- 30 min and 109 +/- 61 min, respectively. In 15 subjects, the symptoms disappeared during recompression to ground level followed by 2 h of oxygen breathing. In the remaining 14 cases, the symptoms disappeared with immediate hyperbaric oxygen treatment. CONCLUSIONS: Pulmonary altitude DCS or chokes is confirmed to be a rare condition. Our data showed that when diagnosed early, recompression to ground level pressure and/or hyperbaric oxygen treatment was 100% successful in resolving the symptoms.

Description: Targeted gene silencing in mammalian cells by RNA interference (RNAi) using small interfering RNAs (siRNAs) was recently described by Elbashir et al. (S. M. Elbashir et al., Nature (Lond.), 411: 494-498, 2001). We have used this methodology in several human cell strains to reduce expression of the Prkdc (DNA-PKcs) gene coding for the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs) that is involved in the nonhomologous end joining of DNA double-strand breaks. We have also demonstrated a radiosensitization for several phenotypic endpoints of radiation damage. In low-passage normal human fibroblasts, siRNA knock-down of DNA-PKcs resulted in a reduced capacity for restitution of radiation-induced interphase chromosome breaks as measured by premature chromosome condensation, an increased yield of acentric chromosome fragments at the first postirradiation mitosis, and an increased radiosensitivity for cell killing. For three strains of related human lymphoblasts, DNA-PKcs-targeted siRNA transfection resulted in little or no increase in radiosensitivity with respect to cell killing, a 1.5-fold decrease in induced mutant yield in TK6- and p53-null NH32 cells, but about a 2-fold increase in induced mutant yield in p53-mutant WTK1 cells at both the hypoxanthine quanine phosphoribosyl transferase (hprt) and the thymidine kinase loci.

Description: Radiation measurements made onboard the MIR Orbital Station have spanned nearly a decade and covered two solar cycles, including one of the largest solar particle events, one of the largest magnetic storms, and a mean solar radio flux level reaching 250 x 10(4) Jansky that has been observed in the last 40 years. The cosmonaut absorbed dose rates varied from about 450 microGy day-1 during solar minimum to approximately half this value during the last solar maximum. There is a factor of about two in dose rate within a given module, and a similar variation from module to module. The average radiation quality factor during solar minimum, using the ICRP-26 definition, was about 2.4. The drift of the South Atlantic Anomaly was measured to be 6.0 +/- 0.5 degrees W, and 1.6 +/- 0.5 degrees N. These measurements are of direct applicability to the International Space Station. This paper represents a comprehensive review of Mir Space Station radiation data available from a variety of sources. c2002 Elsevier Science Ltd. All rights reserved.

Description: Passive radiation dosimeters were exposed aboard the Mir Orbital Station over a substantial portion of the solar cycle in order to measure the change in dose and dose equivalent rates as a function of time. During solar minimum, simultaneous measurements of the radiation environment throughout the habitable volume of the Mir were made using passive dosimeters in order to investigate the effect of localized shielding on dose and dose equivalent. The passive dosimeters consisted of a combination of thermoluminescent detectors to measure absorbed dose and CR-39 PNTDs to measure the linear energy transfer (LET) spectrum from charged particles of LET infinity H2O 〉 or = 5 keV/micrometers. Results from the two detector types were then combined to yield mean total dose rate, mean dose equivalent rate, and average quality factor. Contrary to expectations, both dose and dose equivalent rates measured during May-October 1991 near solar maximum were higher than similar measurements carried out in 1996-1997 during solar minimum. The elevated dose and dose equivalent rates measured in 1991 were probably due to a combination of intense solar activity, including a large solar particle event on 9 June 1991, and the temporary trapped radiation belt created in the slot region by the solar particle event and ensuing magnetic storm of 24 March 1991. During solar minimum, mean dose and dose equivalent rates were found to vary by factors of 1.55 and 1.37, respectively, between different locations through the interior of Mir. More heavily shielded locations tended to yield lower total dose and dose equivalent rates, but higher average quality factor than did more lightly shielding locations. However, other factors such as changes in the immediate shielding environment surrounding a given detector location, changes in the orientation of the Mir relative to its velocity vector, and changes in the altitude of the station also contributed to the variation. Proton and neutron-induced target fragment secondaries, not primary galactic cosmic rays, were found to dominate the LET spectrum above 100 keV/micrometers. This indicates that in low earth orbit, trapped protons in the South Atlantic Anomaly are responsible for the major fraction of the total dose equivalent. c2002 Elsevier Science Ltd. All rights reserved.

Description: This paper reports results from the first measurements made on the exterior of a LEO spacecraft of mean dose equivalent rate and average quality factor as functions of shielding depth for shielding less than 1 g/cm2 Al equivalent. Two sets of measurements were made on the outside of the Mir Orbital Station; one near solar maximum in June 1991 and one near solar minimum in 1997. Absorbed dose was measured using stacks of TLDs. LET spectrum from charged particles of LET infinity H2O 〉 o r= 5keV/micrometers was measured using stacks of CR-39 PNTDs. Results from the TLD and PNTD measurements at a given shielding depth were combined to yield mean total dose rate, mean dose equivalent rate, and average quality factor. Measurements made near solar maximum tend to be greater than those made during solar minimum. Both mean dose rate and mean dose equivalent rate decrease by nearly four orders of magnitude within the first g/cm2 shielding illustrating the attenuation of both trapped electrons and low-energy trapped protons. In order to overcome problems with detector saturation after standard chemical processing, measurement of LET spectrum in the least shielded CR-39 PNTD layer (0.005 g/cm2 Al) was carried out using an atomic force microscope. c2002 Elsevier Science Ltd. All rights reserved.

Description: INTRODUCTION: Since strenuous exercise for 10 min during preoxygenation was shown to provide better protection from decompression sickness (DCS) incidence than resting preoxygenation, a logical question was: would a longer period of strenuous exercise improve protection even further? HYPOTHESIS: Increased strenuous exercise duration during preoxygenation increases DCS protection. METHODS: There were 60 subjects, 30 men and 30 women, who were exposed to 9,144 m (4.3 psia) for 4 h while performing mild, upper body exercise. Before the exposures, each subject performed three preoxygenation profiles on different days in balanced order: a 90-min resting preoxygenation control; a 240-min resting preoxygenation control; and a 90-min preoxygenation including exercise during the first 15 min. The subjects were monitored at altitude for venous gas emboli (VGE) with an echo-imaging system and observed for signs and symptoms of DCS. RESULTS: There were no significant differences in occurrence of DCS following any of the three preoxygenation procedures. Results were also comparable to an earlier report of 42% DCS with a 60-min preoxygenation including a 10-min exercise. There was no difference between VGE incidence in the comparison of protection offered by a 90-min preoxygenation with or without 13 min of strenuous exercise. The DCS incidence following a 240-min resting preoxygenation, 40%, was higher than observed during NASA studies and nearly identical with the earlier 42% DCS after a 60-min preoxygenation including exercise during the first 10 min. CONCLUSION: The protection offered by a 10 min exercise in a 60-min preoxygenation was not increased with extension of the preoxygenation exercise period to 15 min in a 90-min preoxygenation, indicating an upper time limit to the beneficial effects of strenuous exercise.

Description: The effects of gravitational unloading with or without intact neural activity and/or tension development on myosin heavy chain (MHC) composition, cross-sectional area (CSA), number of myonuclei, and myonuclear domain (cytoplasmic volume per myonucleus ratio) in single fibers of both slow and fast muscles of rat hindlimbs are reviewed briefly. The atrophic response to unloading is generally graded as follows: slow extensors 〉 fast extensors 〉 fast flexors. Reduction of CSA is usually greater in the most predominant fiber type of that muscle. The percentage of fibers expressing fast MHC isoforms increases in unloaded slow but not fast muscles. Myonuclear number per mm of fiber length and myonuclear domain is decreased in the fibers of the unloaded predominantly slow soleus muscle, but not in the predominantly fast plantaris. Decreases in myonuclear number and domain, however, are observed in plantaris fibers when tenotomy, denervation, or both are combined with hindlimb unloading. All of these results are consistent with the view that a major factor for fiber atrophy is an inhibition or reduction of loading of the hindlimbs. These data also indicate that predominantly slow muscles are more responsive to unloading than predominantly fast muscles. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

Description: Although the space radiation environment consists predominantly of energetic protons, astronauts inside a spacecraft are chronically exposed to both primary particles as well as secondary particles that are generated when the primary particles penetrate the spacecraft shielding. Secondary neutrons and secondary charged particles can have an LET value that is greater than the primary protons and, therefore, produce a higher relative biological effectiveness (RBE). Using the accelerator facility at Loma Linda University, we exposed human lymphocytes in vitro to 250 MeV protons with doses ranging from 0 to 60 cGy at three different dose rates: a low dose rate of 7.5 cGy/h, an intermediate dose rate of 30 cGy/h and a high dose rate of 70 cGy/min. The effect of 15 g/cm2 aluminum shielding on the induction of chromosome aberrations was investigated for each dose rate. After exposure, lymphocytes were incubated in growth medium containing phytohemagglutinin (PHA) and chromosome spreads were collected using a chemical-induced premature chromosome condensation (PCC) technique. Aberrations were analyzed using the fluorescence in situ hybridization (FISH) technique with three different colored chromosome-painting probes. The frequency of reciprocal and complex-type chromosome exchanges were compared in shielded and unshielded samples. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

Description: Proper assessments of spacecraft shielding requirements and concomitant estimates of risk to critical body organs of spacecraft crews from energetic space radiation require accurate, quantitative methods of characterizing the compositional changes in these radiation fields as they pass through the spacecraft and overlying tissue. When estimating astronaut radiation organ doses and dose equivalents it is customary to use the Computerized Anatomical Man (CAM) model of human geometry to account for body self-shielding. Usually, the distribution for the 50th percentile man (175 cm height; 70 kg mass) is used. Most male members of the U.S. astronaut corps are taller and nearly all have heights that deviate from the 175 cm mean. In this work, estimates of critical organ doses and dose equivalents for interplanetary crews exposed to an event similar to the October 1989 solar particle event are presented for male body sizes that vary from the 5th to the 95th percentiles. Overall the results suggest that calculations of organ dose and dose equivalent may vary by as much as approximately 15% as body size is varied from the 5th to the 95th percentile in the population used to derive the CAM model data. c2002 Published by Elsevier Science Ltd on behalf of COSPAR.

Description: The radiation risk to astronauts has always been based on measurements using passive thermoluminescent dosimeters (TLDs). The skin dose is converted to dose equivalent using an average radiation quality factor based on model calculations. The radiological risk estimates, however, are based on organ and tissue doses. This paper describes results from the first space flight (STS-91, 51.65 degrees inclination and approximately 380 km altitude) of a fully instrumented Alderson Rando phantom torso (with head) to relate the skin dose to organ doses. Spatial distributions of absorbed dose in 34 1-inch-thick sections measured using TLDs are described. There is about a 30% change in dose as one moves from the front to the back of the phantom body. Small active dosimeters were developed specifically to provide time-resolved measurements of absorbed dose rates and quality factors at five organ locations (brain, thyroid, heart/lung, stomach and colon) inside the phantom. Using these dosimeters, it was possible to separate the trapped-proton and the galactic cosmic radiation components of the doses. A tissue-equivalent proportional counter (TEPC) and a charged-particle directional spectrometer (CPDS) were flown next to the phantom torso to provide data on the incident internal radiation environment. Accurate models of the shielding distributions at the site of the TEPC, the CPDS and a scalable Computerized Anatomical Male (CAM) model of the phantom torso were developed. These measurements provided a comprehensive data set to map the dose distribution inside a human phantom, and to assess the accuracy and validity of radiation transport models throughout the human body. The results show that for the conditions in the International Space Station (ISS) orbit during periods near the solar minimum, the ratio of the blood-forming organ dose rate to the skin absorbed dose rate is about 80%, and the ratio of the dose equivalents is almost one. The results show that the GCR model dose-rate predictions are 20% lower than the observations. Assuming that the trapped-belt models lead to a correct orbit-averaged energy spectrum, the measurements of dose rates inside the phantom cannot be fully understood. Passive measurements using 6Li- and 7Li-based detectors on the astronauts and inside the brain and thyroid of the phantom show the presence of a significant contribution due to thermal neutrons, an area requiring additional study.

Description: The purpose of this study was to examine site- and compartment-specific changes in bone induced by hindlimb unloading (HU) in the mature adult male rat (6 months old). Tibiae, femora, and humeri were removed after 14, 21, and 28 days of HU for determination of bone mineral density (BMD) and geometry by peripheral quantitative computed tomography (pQCT), mechanical properties, and bone formation rate (BFR), and compared with baseline (0 day) and aging (28 day) controls. HU resulted in 20%-21% declines in cancellous BMD at the proximal tibia and femoral neck after 28 day HU vs. 0 day controls (CON). Cortical shell BMD at these sites was greater (by 4%-6%) in both 28 day HU and 28 day CON vs. 0 day CON animals, and nearly identical to that gain seen in the weight-bearing humerus. Mechanical properties at the proximal tibia exhibited a nonsignificant decline after HU vs. those of 0 day CON rats. At the femoral neck, a 10% decrement was noted in ultimate load in 28 day HU rats vs. 28 day CON animals. Middiaphyseal tibial bone increased slightly in density and area during HU; no differences in structural and material properties between 28 day HU and 28 day CON rats were noted. BFR at the tibial midshaft was significantly lower (by 90%) after 21 day HU vs. 0 day CON; this decline was maintained throughout 28 day HU. These results suggest there are compartment-specific differences in the mature adult skeletal response to hindlimb unloading, and that the major impact over 28 days of unloading is on cancellous bone sites. Given the sharp decline in BFR for midshaft cortical bone, it appears likely that deficits in BMD, area, or mechanical properties would develop with longer duration unloading.

Description: Regulated animal growth occurred following a single electroporated injection of a mixture of two plasmids (10 microg of DNA), one expressing the GeneSwitch regulator protein, the other an inducible growth hormone releasing hormone (GHRH) gene, into the tibialis anterior muscles of adult SCID mice. Administration of the ligand mifepristone (MFP) up-regulated GHRH expression, as shown by elevations of IGF-I levels, and when MFP dosing was withdrawn, IGF-I returned to baseline levels. Five cycles of IGF-I induction were observed during a five-month period. Chronic MFP dosing for 25 days increased lean body mass, weight gain, and bone mineral density significantly compared with non-MFP treated controls. In summary, long-term drug-regulated GHRH expression was achieved following plasmid-based gene therapy, and chronic induction of GHRH expression in adult animals led to improvements in weight gain and body composition.

Description: Previous studies established that vestibular reflexes can have two adapted states (e.g., gains) simultaneously, and that a context cue (e.g., vertical eye position) can switch between the two states. Our earlier work demonstrated this phenomenon of context-specific adaptation for saccadic eye movements: we asked for gain decrease in one context state and gain increase in another context state, and then determined if a change in the context state would invoke switching between the adapted states. Horizontal and vertical eye position and head orientation could serve, to varying degrees, as cues for switching between two different saccade gains. In the present study, we asked whether gravity magnitude could serve as a context cue: saccade adaptation was performed during parabolic flight, which provides alternating levels of gravitoinertial force (0 g and 1.8 g). Results were less robust than those from ground experiments, but established that different saccade magnitudes could be associated with different gravity levels.

Description: A numerical model of the cardiovascular system was used to quantify the influences on cardiac function of intrathoracic pressure and intravascular and intraventricular hydrostatic pressure, which are fundamental biomechanical stimuli for orthostatic response. The model included a detailed arterial circulation with lumped parameter models of the atria, ventricles, pulmonary circulation, and venous circulation. The venous circulation was divided into cranial, central, and caudal regions with nonlinear compliance. Changes in intrathoracic pressure and the effects of hydrostatic pressure were simulated in supine, launch, sitting, and standing postures for 0, 1, and 1.8 G. Increasing intrathoracic pressure experienced with increasing gravity caused 12% and 14% decreases in cardiac output for 1 and 1.8 G supine, respectively, compared to 0 G. Similar results were obtained for launch posture, in which the effects of changing intrathoracic pressure dominated those of hydrostatic pressure. Compared to 0 G, cardiac output decreased 0.9% for 1 G launch and 15% for 1.8 G launch. In sitting and standing, the position of the heart above the hydrostatic indifference level caused the effects of changing hydrostatic pressure to dominate those of intrathoracic pressure. Compared to 0 G, cardiac output decreased 13% for 1 G sitting and 23% for 1.8 G sitting, and decreased 17% for 1 G standing and 31% for 1.8 G standing. For a posture change from supine to standing in 1 G, cardiac output decreased, consistent with the trend necessary to explain orthostatic intolerance in some astronauts during postflight stand tests. Simulated lower body negative pressure (LBNP) in 0 G reduced cardiac output and mean aortic pressure similar to I G standing, suggesting that LBNP provides at least some cardiovascular stimuli that may be useful in preventing postflight orthostatic intolerance. A unifying concept, consistent with the Frank-Starling mechanism of the heart, was that cardiac output was proportional to cardiac diastolic transmural pressure for all postures and gravitational accelerations.

Description: G-induced vestibular dysfunction (GIVD) is a condition well known to aircraft pilots who experience high positive and negative G loads during unlimited-aerobatic competitions and air-show demonstrations. After landing and walking from their aircraft, pilots with GIVD manifest an extremely unstable gait, which they call the wobblies. This article includes a report of one such case of GIVD, which to the author's knowledge is the first published case report of this condition in the medical literature. The author also discusses what is known and theorized about the pathogenesis of GIVD, and he reviews its diagnosis, treatment, and prevention.

Description: Changes in the material characteristics of bone marrow with aging can be a significant source of error in measurements of bone density when using X-ray and ultrasound imaging modalities. In the context of computed tomography, dual-energy computed techniques have been used to correct for changes in marrow composition. However, dual-energy quantitative computed tomography (DE-QCT) protocols, while increasing the accuracy of the measurement, reduce the precision and increase the radiation dose to the patient in comparison to single-energy quantitative computed tomography (SE-QCT) protocols. If the attenuation properties of the marrow for a particular bone can be shown to be relatively constant with age, it should be possible to use single-energy techniques without experiencing errors caused by unknown marrow composition. Marrow was extracted by centrifugation from 10 mm thick frontal sections of 34 adult cadaver calcanei (28 males, 6 females, ages 17-65 years). The density and energy-dependent linear X-ray attenuation coefficient of each marrow sample were determined. For purposes of comparing our results, we then computed an effective CT number at two GE CT/i scan voltages (80 and 120 kVp) for each specimen. The coefficients of variation for the density, CT number at 80 kVp and CT number at 120 kVp were each less than 1%, and the parameters did not change significantly with age (p 〉 0.2, r2 〈 0.02, power 〉 0.8 where the minimum acceptable r2 = 0.216). We could demonstrate no significant gender-associated differences in these relationships. These data suggest that calcaneal bone marrow X-ray attenuation properties and marrow density are essentially constant from the third through sixth decades of life.

Description: BACKGROUND: When an astronaut walks or runs on a treadmill in microgravity, a subject load device (SLD) is used to return him or her back to the treadmill belt. The gravity replacement load (GRL) in the SLD is transferred, via a harness, to the pelvis and/or the shoulders. This research compared comfort and ground reaction forces during treadmill running in a microgravity locomotion simulator at GRLs of 60%, 80%, and 100% of body weight (BW). Two harness designs (shoulder springs only (SSO) and waist and shoulder springs (WSS)) were used. HYPOTHESES: 1) The 100% BW gravity replacement load conditions would be comfortably tolerated and would result in larger ground reaction forces and loading rates than the lower load conditions, and 2) the WSS harness would be more comfortable than the SSO harness. METHODS: Using the Penn State Zero Gravity Locomotion Simulator (ZLS), 8 subjects ran at 2.0 m x s(-1) (4.5 mph) for 3 min at each GRL setting in each harness. Subjective ratings of harness comfort, ground reaction forces, and GRL data were collected during the final minute of exercise. RESULTS: The 100% BW loading conditions were comfortably tolerated (2.3 on a scale of 0-10), although discomfort increased as the GRL increased. There were no overall differences in perceived comfort between the two harnesses. The loading rates (27.1, 33.8, 39.1 BW x s(-1)) and the magnitudes of the first (1.0, 1.4, 1.6 BW) and second (1.3, 1.7, 1.9 BW) peaks of the ground reaction force increased with increasing levels (60, 80, 100% BW respectively) of GRL. CONCLUSIONS: Subjects were able to tolerate a GRL of 100% BW well. The magnitude of the ground reaction force peaks and the loading rate is directly related to the magnitude of the GRL.

Description: As a 'window to the body', the eye offers the opportunity to use light in various forms to detect ocular and systemic abnormalities long before clinical symptoms appear and help develop preventative/therapeutic countermeasures early. The effects of space travel on human body are similar to those of normal aging. For example, radiation exposure in space could lead to formation of cataracts and cancer by damaging the DNA and causing gene mutation. Additionally, the zero-gravity environment causes fluid shifts in the upper extremities of the body and changes the way blood flows and organ system performs. Here on Earth, cataract, age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma are major eye diseases and are expected to double in next two decades. To detect, prevent, and treat untoward effects of prolonged space travel in real-time requires the development of non-invasive diagnostic technologies that are compact and powerful. We are developing fiber-optic sensors to evaluate the ocular tissues in health, aging, and disease employing the techniques of dynamic light scattering (cataract, uveitis, Alzheimer's, glaucoma, DR, radiation damage, refractive surgery outcomes), auto-fluorescence (aging, DR), laser-Doppler flowmetry (choroidal blood flow), Raman spectroscopy (AMD), polarimetry (diabetes), and retinal oximetry (occult blood loss). The non-invasive feature of these technologies integrated in a head-mounted/goggles-like device permits frequent repetition of tests, enabling evaluation of the results to therapy that may ultimately be useful in various telemedicine applications on Earth and in space.

Description: The International Space Station will provide a "World Class" environment for microgravity research. Ensuring this environment requires care in all aspects of its design. These aspects include consideration of the acceleration at near-orbit-tune-periods, such as gravity gradients and station drag, as well as controlling station structural dynamic modes, mechanical disturbances, and crew disturbances. Station designers must also ensure that the required acceleration environment is provided for long duration. The microgravity requirements placed on ISS will be reviewed, along with major considerations for achieving such an environment. Further, a description of the Space Station program strategy and implementation for meeting those requirements will be discussed. c2002 Published by Elsevier Science Ltd.

Description: PURPOSE: The purpose of this study was to determine whether hindlimb suspension (which simulates the effects of microgravity) results in impaired hemodynamic responses to heat stress or alterations in mesenteric small artery sympathetic nerve innervation. METHODS: Over 28 d, 16 male Sprague-Dawley rats were hindlimb-suspended, and 13 control rats were housed in the same type of cage. After the treatment, mean arterial pressure (MAP), colonic temperature (Tcol), and superior mesenteric and iliac artery resistances (using Doppler flowmetry) were measured during heat stress [exposure to 42 degrees C until the endpoint of 80 mm Hg blood pressure was reached (75 +/- 9 min); endpoint Tcore = 43.6 +/- 0.2] while rats were anesthetized (sodium pentobarbital, 50 mg x kg(-1) BW). RESULTS: Hindlimb-suspended and control rats exhibited similar increases in Tcol, MAP, and superior mesenteric artery resistance, and similar decreases in iliac resistance during heat stress (endpoint was a fall in MAP below 80 mm Hg). Tyrosine hydroxylase immunostaining indicated similar sympathetic nerve innervation in small mesenteric arteries from both groups. CONCLUSION: Hindlimb suspension does not alter the hemodynamic or thermoregulatory responses to heat stress in the anesthetized rat or mesenteric sympathetic nerve innervation, suggesting that this sympathetic pathway is intact.

Description: Radiation exposures are typically characterized by two quantities. The first is the absorbed dose, or the energy deposited per unit mass for specific types of radiation passing through specified materials. The same amount of energy deposited in material by two different types of radiation, however, can result in two different levels of risk. Because of this, for the purpose of radiation protection operations, absorbed dose is modified by a second factor intended to normalize the risk associated with a given exposure. We present here an inter-comparison of methods for this modification. First is the radiation quality factor (Q), as defined by ICRP publication 60. This quantity is related functionally to the unrestricted linear energy transfer (LET) of a given radiation, and is multiplied by the absorbed dose to derive the dose equivalent (H). The second method for modifying absorbed dose is the radiation weighting factor, also given in ICRP-60, or as modified in NCRP report 115. To implement the weighting factor, the absorbed dose resulting from incidence of a particular radiation is multiplied by a factor assigned to that type of radiation, giving the equivalent dose. We compare calculations done based on identical fields of radiation representative of that encountered by the MIR space station, applying each of these two methods. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

Description: Recent studies suggest that an underlying mechanism for susceptibility of patients and astronauts to presyncope includes hypoadrenergic responses to orthostatic stress. However, data used to reach this conclusion are open to various interpretations. In this report, maintenance of sympathetic neural activity (MSNA; peroneal nerve microneurography) during -60 mmHg lower body negative pressure (LBNP) was associated with maintenance of orthostatic tolerance, and disappearance of MSNA was associated with hypotension and pre-syncope. However, MSNA was substantially higher during progressive increases of negative pressure in the presyncopal subject, compared to the non-presyncopal subjects. The data from this case report question the notion that orthostatic hypotension occurs due to inadequate sympathetic neural activation during orthostatic stress in apparently normal, healthy subjects.

Description: To determine the influence of dietary calcium on spaceflight-induced alterations in calcium metabolism and blood pressure (BP), 9-wk-old spontaneously hypertensive rats, fed either high- (2%) or low-calcium (0.02%) diets, were flown on an 18-day shuttle flight. On landing, flight animals had increased ionized calcium (P 〈 0.001), elevated parathyroid hormone levels (P 〈 0.001), reduced calcitonin levels (P 〈 0.05), unchanged 1,25(OH)(2)D(3) levels, and elevated skull (P 〈 0.01) and reduced femur bone mineral density. Basal and thrombin-stimulated platelet free calcium (intracellular calcium concentration) were also reduced (P 〈 0.05). There was a tendency for indirect systolic BP to be reduced in conscious flight animals (P = 0.057). However, mean arterial pressure was elevated (P 〈 0.001) after anesthesia. Dietary calcium altered all aspects of calcium metabolism (P 〈 0.001), as well as BP (P 〈 0.001), but the only interaction with flight was a relatively greater increase in ionized calcium in flight animals fed low- compared with high-calcium diets (P 〈 0.05). The results indicate that 1) flight-induced disruptions of calcium metabolism are relatively impervious to dietary calcium in the short term, 2) increased ionized calcium did not normalize low-calcium-induced elevations of BP, and 3) parathyroid hormone was paradoxically increased in the high-calcium-fed flight animals after landing.

Description: Vascular contractile hyporesponsiveness is an important mechanism underlying orthostatic intolerance after microgravity. Baroreceptor reflexes can modulate both pulmonary resistance and capacitance function and thus cardiac output. We hypothesized, therefore, that pulmonary vasoreactivity is impaired in the hindlimb-unweighted (HLU) rat model of microgravity. Pulmonary artery (PA) contractile responses to phenylephrine (PE) and U-46619 (U4) were significantly decreased in the PAs from HLU vs. control (C) animals. N(G)-nitro-L-arginine methyl ester (10(-5) M) enhanced the contractile responses in the PA rings from both C and HLU animals and completely abolished the differential responses to PE and U4 in HLU vs. C animals. Vasorelaxant responses to ACh were significantly enhanced in PA rings from HLU rats compared with C. Moreover, vasorelaxant responses to sodium nitroprusside were also significantly enhanced. Endothelial nitric oxide synthase (eNOS) and soluble guanlyl cyclase expression were significantly enhanced in PA and lung tissue from HLU rats. In marked contrast, the expression of inducible nitric oxide synthase was unchanged in lung tissue. These data support the hypothesis that vascular contractile responsiveness is attenuated in PAs from HLU rats and that this hyporesponsiveness is due at least in part to increased nitric oxide synthase activity resulting from enhanced eNOS expression. These findings may have important implications for blood volume distribution and attenuated stroke volume responses to orthostatic stress after microgravity exposure.

Description: The purpose of this study was to test the hypothesis that regional brain blood flow and vascular resistance are altered by acute and chronic head-down tail suspension (HDT). Regional cerebral blood flow, arterial pressure, heart rate, and vascular resistance were measured in a group of control rats during normal standing and following 10 min of HDT and in two other groups of rats after 7 and 28 days of HDT. Heart rate was not different among conditions, whereas mean arterial pressure was elevated at 10 min of HDT relative to the other conditions. Total brain blood flow was reduced from that during standing by 48, 24, and 27% following 10 min and 7 and 28 days of HDT, respectively. Regional blood flows to all cerebral tissues and the eyes were reduced with 10 min of HDT and remained lower in the eye, olfactory bulbs, left and right cerebrum, thalamic region, and the midbrain with 7 and 28 days of HDT. Total brain vascular resistance was 116, 44, and 38% greater following 10 min and 7 and 28 days of HDT, respectively, relative to that during control standing. Vascular resistance was elevated in all cerebral regions with 10 min of HDT and remained higher than control levels in most brain regions. These results demonstrate that HDT results in chronic elevations in total and regional cerebral vascular resistance, and this may be the underlying stimulus for the HDT-induced smooth muscle hypertrophy of cerebral resistance arteries.

Description: We used Ca2+-activated skinned muscle fibers to test the hypothesis that unilateral lower leg suspension (ULLS) alters cross-bridge mechanisms of muscle contraction. Soleus and gastrocnemius biopsies were obtained from eight subjects before ULLS, immediately after 12 days of ULLS (post-0 h), and after 6 h of reambulation (post-6 h). Post-0 h soleus fibers expressing type I myosin heavy chain (MHC) showed significant reductions in diameter, absolute and specific peak Ca2+-activated force, unloaded shortening velocity, and absolute and normalized peak power. Fibers obtained from the gastrocnemius were less affected by ULLS, particularly fibers expressing fast MHC isoforms. Post-6 h soleus fibers produced less absolute and specific peak force than did post-0 h fibers, suggesting that reambulation after ULLS induced cell damage. Like bed rest and spaceflight, ULLS primarily affects soleus over gastrocnemius fibers. However, in contrast to these other models, slow soleus fibers obtained after ULLS showed a decrease in unloaded shortening velocity and a greater reduction in specific force.

Description: It is important to know whether the human population includes genetically predisposed radiosensitive subsets. In vitro studies have shown that cells from individuals homozygous for ataxia telangiectasia (A-T) are much more radiosensitive than cells from unaffected individuals. Although cells heterozygous for the ATM gene (ATM(+/-)) may be slightly more radiosensitive in vitro, it remained to be determined whether the greater susceptibility of ATM(+/-) cells translates into an increased sensitivity for late effects in vivo, though there is a suggestion that radiotherapy patients that are heterozygous for the ATM gene may be more at risk of developing late normal tissue damage. We chose cataractogenesis in the lens as a means to assay for the effects of ATM deficiency in a late-responding tissue. One eye of wild-type, Atm heterozygous and homozygous knockout mice was exposed to 0.5-, 1.0-, 2.0-, or 4.0-Gy x rays. The animals were followed weekly for cataract development by conventional slit-lamp biomicroscopy. Cataract development in the animals of all three groups was strongly dependent on dose. The lenses of homozygous mice were the first to opacify at any given dose. Most important in the present context is that cataracts appeared earlier in the heterozygous versus wild-type animals. The data suggest that ATM heterozygotes in the human population may also be radiosensitive. This may influence the choice of individuals destined to be exposed to higher than normal doses of radiation, such as astronauts, and may also suggest that radiotherapy patients who are ATM heterozygotes could be predisposed to increased late normal tissue damage.

Description: BACKGROUND: There are large individual differences in susceptibility to motion sickness. Attempts to predict who will become motion sick have had limited success. In the present study, we examined gender differences in resting levels of salivary amylase and total protein, cardiac interbeat intervals (R-R intervals), and a sympathovagal index and evaluated their potential to correctly classify individuals into two motion sickness severity groups. METHODS: Sixteen subjects (10 men and 6 women) flew four sets of 10 parabolas aboard NASA's KC-135 aircraft. Saliva samples for amylase and total protein were collected preflight on the day of the flight and motion sickness symptoms were recorded during each parabola. Cardiovascular parameters were collected in the supine position 1-5 days before the flight. RESULTS: There were no significant gender differences in sickness severity or any of the other variables mentioned above. Discriminant analysis using salivary amylase, R-R intervals and the sympathovagal index produced a significant Wilks' lambda coefficient of 0.36, p=0.006. The analysis correctly classified 87% of the subjects into the none-mild sickness or the moderate-severe sickness group. CONCLUSIONS: The linear combination of resting levels of salivary amylase, high-frequency R-R interval levels, and a sympathovagal index may be useful in predicting motion sickness severity.

Description: BACKGROUND: A major challenge for flight crews is the need to maintain vigilance during long, highly automated nighttime flights. No system currently exists to assist in managing alertness, and countermeasure options are limited. Surveys reveal many pilots use breaks as an in-flight countermeasure, but there have been no controlled studies of their effectiveness. HYPOTHESIS: We hypothesized that brief, regular breaks could improve alertness and performance during an overnight flight. METHOD: A 6-h, uneventful, nighttime flight in a Boeing 747-400 flight simulator was flown by fourteen two-man crews. The 14 subjects in the treatment group received 5 short breaks spaced hourly during cruise; the 14 subjects in the control group received 1 break in the middle of cruise. Continuous EEG/EOG, subjective sleepiness, and psychomotor vigilance performance data were collected. RESULTS: During the latter part of the night, the treatment group showed significant reductions for 15 min post-break in slow eye movements, theta-band activity, and unintended sleep episodes compared with the control group. The treatment group reported significantly greater subjective alertness for up to 25 min post-break, with strongest effects near the time of the circadian trough. There was no evidence of objective vigilance performance improvement at 15-25 min post-break, with expected performance deterioration occurring due to elevated sleep drive and circadian time. CONCLUSIONS: The physiological and subjective data indicate the breaks reduced nighttime sleepiness for at least 15 min post-break and may have masked sleepiness for up to 25 min, suggesting the potential usefulness of short-duration breaks as an in-flight fatigue countermeasure.

Description: BACKGROUND: Decompression, as occurs with aviators and astronauts undergoing high altitude operations or with deep-sea divers returning to surface, can cause gas bubbles to form within the organism. Pressure changes to evoke bubble formation in vivo during depressurization are several orders of magnitude less than those required for gas phase formation in vitro in quiescent liquids. Preformed micronuclei acting as "seeds" have been proposed, dating back to the 1940's. These tissue gas micronuclei have been attributed to a minute gas phase located in hydrophobic cavities, surfactant-stabilized microbubbles, or arising from musculoskeletal activity. The lifetimes of these micronuclei have been presumed to be from a few minutes to several weeks. HYPOTHESIS: The greatest incidence of venous gas emboli (VGE) will be detected by precordial Doppler ultrasound with depressurization immediately following lower extremity exercise, with progressively reduced levels of VGE observed as the interval from exercise to depressurization lengthens. METHODS: In a blinded cross-over design, 20 individuals (15 men, 5 women) at sea level exercised by performing knee-bend squats (150 knee flexes over 10 min, 235-kcal x h(-1)) either at the beginning, middle, or end of a 2-h chair-rest period without an oxygen prebreathe. Seated subjects were then depressurized to 6.2 psia (6,706 m or 22,000 ft altitude equivalent) for 120 min with no exercise performed at altitude. RESULTS: Of the 20 subjects with VGE in the pulmonary artery, 10 demonstrated a greater incidence of bubbles with exercise performed just prior to depressurization, compared with decreasing bubble grades and incidence as the interval of rest increased prior to depressurization. No decompression illness was reported. CONCLUSIONS: There is a significant increase in decompression-induced bubble formation at 6.2 psia when lower extremity exercise is performed just prior to depressurization as compared with longer rest intervals. Analysis indicated that micronuclei half-life is on the order of an hour under these hypobaric conditions.

Description: Extravehicular activity (EVA), i.e., exercise performed under unique environmental conditions, is indispensable for supporting daily living in weightlessness and for further space exploration. From 1965-1996 an average of 20 h x yr(-1) were spent performing EVA. International Space Station (ISS) assembly will require 135 h x yr(-1) of EVA, and 138 h x yr(-1) is planned for post-construction maintenance. The extravehicular mobility unit (EMU), used to protect astronauts during EVA, has a decreased pressure of 4.3 psi that could increase astronauts' risk of decompression sickness (DCS). Exercise in and repeated exposure to this hypobaria may increase the incidence of DCS, although weightlessness may attenuate this risk. Exercise thermoregulation within the EMU is poorly understood; the liquid cooling garment (LCG), worn next to the skin and designed to handle thermal stress, is manually controlled. Astronauts may become dehydrated (by up to 2.6% of body weight) during a 5-h EVA, further exacerbating the thermoregulatory challenge. The EVA is performed mainly with upper body muscles; but astronauts usually exercise at only 26-32% of their upper body maximal oxygen uptake (VO2max). For a given ground-based work task in air (as opposed to water), the submaximal VO2 is greater while VO2max and metabolic efficiency are lower during ground-based arm exercise as compared with leg exercise, and cardiovascular responses to exercise and training are also different for arms and legs. Preflight testing and training, whether conducted in air or water, must account for these differences if ground-based data are extrapolated for flight requirements. Astronauts experience deconditioning during microgravity resulting in a 10-20% loss in arm strength, a 20-30% loss in thigh strength, and decreased lower-body aerobic exercise capacity. Data from ground-based simulations of weightlessness such as bed rest induce a 6-8% decrease in upper-body strength, a 10-16% loss in thigh extensor strength, and a 15-20% decrease in lower-body aerobic exercise capacity. Changes in EVA support systems and training based on a greater understanding of the physiological aspects of exercise in the EVA environment will help to insure the health, safety, and efficiency of working astronauts.

Description: This study was designed to examine the skeletal response to copper depletion and mechanical unloading in mature animals. In a 2 x 2 experimental design, 5.5-mo-old male Sprague-Dawley rats (n = 36) consumed either the control (AIN-93M) or Cu-depletion ((-)Cu) diet beginning 21 d before suspension and throughout the remainder of the study. Half of the rats in each dietary treatment group were either tail-suspended (TS) or kept ambulatory (AMB) for 28 d. Lower bone mineral densities (BMD) of 5th lumbar vertebra (L5) (P 〈 0.05) and femur were observed with (-)Cu and TS, but no differences were noted in the BMD of the humerus. Mechanical strength in the femur and vertebra decreased in response to TS, but were unaffected by copper depletion. Urinary deoxypyridinoline, an index of bone resorption, was significantly greater in TS rats, but unaltered by (-)Cu. No changes in serum or bone alkaline phosphatase activity, an indicator of bone formation, were observed. Our findings suggest that TS and (-)Cu decreased BMD in unloaded femur and vertebra but had no effect on normally loaded humerus. Bone loss with TS appeared to be related to accelerated bone resorption. Alterations in bone metabolism and bone mechanical properties in the mature skeleton resulting from (-)Cu warrant further investigation.

Description: The objective of this study is to develop a model of the cardiovascular system capable of simulating the short-term (〈 or = 5 min) transient and steady-state hemodynamic responses to head-up tilt and lower body negative pressure. The model consists of a closed-loop lumped-parameter representation of the circulation connected to set-point models of the arterial and cardiopulmonary baroreflexes. Model parameters are largely based on literature values. Model verification was performed by comparing the simulation output under baseline conditions and at different levels of orthostatic stress to sets of population-averaged hemodynamic data reported in the literature. On the basis of experimental evidence, we adjusted some model parameters to simulate experimental data. Orthostatic stress simulations are not statistically different from experimental data (two-sided test of significance with Bonferroni adjustment for multiple comparisons). Transient response characteristics of heart rate to tilt also compare well with reported data. A case study is presented on how the model is intended to be used in the future to investigate the effects of post-spaceflight orthostatic intolerance.

Description: The purpose of this study was to quantify precisely aging-induced changes in skeletal perfusion and bone mechanical properties in a small rodent model. Blood flow was measured in conscious juvenile (2 months old), adult (6 months old), and aged (24 months old) male Fischer-344 rats using radiolabeled microspheres. There were no significant differences in bone perfusion rate or vascular resistance between juvenile and adult rats. However, blood flow was lower in aged versus adult rats in the forelimb bones, scapulas, and femurs. To test for functional effects of this decline in blood flow, bone mineral density and mechanical properties were measured in rats from these two age groups. Bone mineral density and cross-sectional moment of inertia in femoral and tibial shafts and the femoral neck were significantly larger in the aged versus adult rats, resulting in increased (+14%-53%) breaking strength and stiffness. However, intrinsic material properties at midshaft of the long bones were 12% to 25% lower in the aged rats. Although these data are consistent with a potential link between decreased perfusion and focal alterations in bone remodeling activity related to clinically relevant bone loss, additional studies are required to establish the mechanisms for this putative relationship.

Description: No abstract available

Description: BACKGROUND: The overall effect of vasoactive drugs on blood pressure is determined by a combination of the direct effect on vascular tone and an indirect baroreflex-mediated effect, a baroreflex buffering of blood pressure. Differences in baroreflex function affect the responsiveness to vasoactive medications, particularly baroreflex buffering of blood pressure; however, the magnitude is not known. METHODS AND RESULTS: We characterized baroreflex function and responses to vasoactive drugs in patients with idiopathic orthostatic intolerance, patients with essential hypertension, patients with monogenic hypertension and brachydactyly, patients with multiple system atrophy, and control subjects. We used phenylephrine sensitivity during ganglionic blockade as a measure of baroreflex buffering. Phenylephrine (25 microg) increased systolic blood pressure 6+/-1.6 mm Hg in control subjects, 6+/-1.1 mm Hg in orthostatic intolerance patients, 18+/-3.9 mm Hg in patients with essential hypertension, 31+/-3.4 mm Hg in patients with monogenic hypertension, and 25+/-3.4 mm Hg in patients with multiple system atrophy. Similar differences in sensitivities between groups were observed with nitroprusside. The sensitivity to vasoactive drugs was highly correlated with baroreflex buffering function and to a lesser degree with baroreflex control of heart rate. In control subjects, sensitivities to nitroprusside and phenylephrine infusions were correlated with baroreflex heart rate control and sympathetic nerve traffic. CONCLUSIONS: Our findings are consistent with an important effect of baroreflex blood pressure buffering on the sensitivity to vasoactive drugs. They suggest that even moderate changes in baroreflex function may have a substantial effect on the sensitivity to vasoactive medications.

Description: Short-radius centrifugation offers a promising and affordable countermeasure to the adverse effects of prolonged weightlessness. However, head movements made in a fast rotating environment elicit Coriolis effects, which seriously compromise sensory and motor processes. We found that participants can adapt to these Coriolis effects when exposed intermittently to high rotation rates and, at the same time, can maintain their perceptual-motor coordination in stationary environments. In this paper, we explore the role of inter-sensory conflict in this adaptation process. Different measures (vertical nystagmus, illusory body tilt, motion sickness) react differently to visual-vestibular conflict and adapt differently. In particular, proprioceptive-vestibular conflict sufficed to adapt subjective parameters and the time constant of nystagmus decay, while retinal slip was required for VOR gain adaptation. A simple correlation between the strength of intersensory conflict and the efficacy of adaptation fails to explain the data. Implications of these findings, which differ from existing data for low rotation rates, are discussed.

Description: The effects of cross-coupled stimuli on the semicircular canals are shown to be influenced by the position of the subject's head with respect to gravity and the axis of rotation, but not by the subject's head position relative to the trunk. Seventeen healthy subjects made head yaw movements out of the horizontal plane while lying on a horizontal platform (MIT short radius centrifuge) rotating at 23 rpm about an earth-vertical axis. The subjects reported the magnitude and duration of the illusory pitch or roll sensations elicited by the cross-coupled rotational stimuli acting on the semicircular canals. The results suggest an influence of head position relative to gravity. The magnitude estimation is higher and the sensation decays more slowly when the head's final position is toward nose-up (gravity in the subject's head x-z-plane) compared to when the head is turned toward the side (gravity in the subject's head y-z-plane). The results are discussed with respect to artificial gravity in space and the possible role of pre-adaptation to cross-coupled angular accelerations on earth.

Description: As a countermeasure to the debilitating physiological effects of weightlessness, astronauts could live continuously in an artificial gravity environment created by slow rotation of an entire spacecraft or be exposed to brief daily "doses" in a short radius centrifuge housed within a non-rotating spacecraft. A potential drawback to both approaches is that head movements made during rotation may be disorienting and nauseogenic. These side effects are more severe at higher rotation rates, especially upon first exposure. Head movements during rotation generate aberrant vestibular stimulation and Coriolis force perturbations of the head-neck motor system. This article reviews our progress toward distinguishing vestibular and motor factors in side effects of rotation, and presents new data concerning the rates of rotation up to which adaptation is possible. We have studied subjects pointing to targets during constant velocity rotation, because these movements generate Coriolis motor perturbations of the arm but do not involve unusual vestibular stimulation. Initially, reaching paths and endpoints are deviated in the direction of the transient lateral Coriolis forces generated. With practice, subjects soon move in straighter paths and land on target once more. If sight of the arm is permitted, adaptation is more rapid than in darkness. Initial arm movement trajectory and endpoint deviations are proportional to Coriolis force magnitude over a range of rotation speeds from 5 to 20 rpm, and there is rapid, complete motor adaptation at all speeds. These new results indicate that motor adaptation to high rotation rates is possible. Coriolis force perturbations of head movements also occur in a rotating environment but adaptation gradually develops over the course of many head movements.

Description: INTRODUCTION: Repeated altitude exposures in a single day occur during special operations parachute training, hypobaric chamber training, unpressurized flight, and extravehicular space activity. Inconsistent and contradictory information exists regarding the risk of decompression sickness (DCS) during such hypobaric exposures. HYPOTHESIS: We hypothesized that four short exposures to altitude with and without ground intervals would result in a lower incidence of DCS than a single exposure of equal duration. METHODS: The 32 subjects were exposed to 3 different hypobaric exposures--condition A: 2 h continuous exposure (control); condition B: four 30-min exposures with descent/ascent but no ground interval between the exposures; condition C: four 30-min exposures with descent/ascent and 60 min of ground interval breathing air between exposures. All exposures were to 25,000 ft with 100% oxygen breathing. Subjects were observed for symptoms of DCS, and precordial monitoring of venous gas emboli (VGE) was accomplished with a SONOS 1000 echo-imaging system. RESULTS: DCS occurred in 19 subjects during A (mean onset 70+/-29 min), 7 subjects in B (60+/-34 min), and 2 subjects in C (40+/-18 min). There was a significant difference in DCS incidence between B and A (p = 0.0015) and C and A (p = 0.0002), but no significant difference between B and C. There were 28 cases of VGE in A (mean onset 30+/-23 min), 21 in B (41+/-35 min), and 21 in C (41+/-32 min) with a significant onset curve difference between B and A and between C and A, but not between B and C. Exposure A resulted in four cases of serious respiratory/neurological symptoms, while B had one and C had none. All symptoms resolved during recompression to ground level. CONCLUSION: Data indicate that repeated simulated altitude exposures to 25,000 ft significantly reduce DCS and VGE incidence compared with a single continuous altitude exposure.

Description: Microgravity and stress of spaceflights result in immune dysfunction. The role of nutrition, especially nucleotide supplementation, has become an area of intensive research and significant interest in immunomodulation for maintenance of cellular immune responses. The studies presented here evaluate the plausibility of administering nucleotides to obviate immune dysfunction in an Earth-based in vivo analog of microgravity as studied in anti-orthostatic tail suspension (AOS) of mice. Mice were divided into three housing groups: group, isolation, and AOS. Mice were fed either control chow diet (CD), or RNA-, adenine-, or uracil-supplemented CD for the 1-wk duration of the experiments. In AOS mice, supplemental nucleotides significantly increased in vivo lymph node proliferation and ex vivo lymphoproliferation response to alloantigen and mitogens, respectively, and interleukin-2 and interferon-gamma production. A lower corticosterone level was observed in uracil-supplemented CD compared with CD. These results suggest that exogenous nucleotide supplementation, especially uracil, of normal diet is beneficial in the maintenance and restoration of the immune response during the microgravity analog conditions.

Description: The International Space Station (ISS) is now a reality with the start of a permanent human presence on board. Radiation presents a serious risk to the health and safety of the astronauts, and there is a clear requirement for estimating their exposures prior to and after flights. Predictions of the dose rate at times other than solar minimum or solar maximum have not been possible, because there has been no method to calculate the trapped-particle spectrum at intermediate times. Over the last few years, a tissue-equivalent proportional counter (TEPC) has been flown at a fixed mid-deck location on board the Space Shuttle in 51.65 degrees inclination flights. These flights have provided data that cover the expected changes in the dose rates due to changes in altitude and changes in solar activity from the solar minimum to the solar maximum of the current 23rd solar cycle. Based on these data, a simple function of the solar deceleration potential has been derived that can be used to predict the galactic cosmic radiation (GCR) dose rates to within +/-10%. For altitudes to be covered by the ISS, the dose rate due to the trapped particles is found to be a power-law function, rho(-2/3), of the atmospheric density, rho. This relationship can be used to predict trapped dose rates inside these spacecraft to +/-10% throughout the solar cycle. Thus, given the shielding distribution for a location inside the Space Shuttle or inside an ISS module, this approach can be used to predict the combined GCR + trapped dose rate to better than +/-15% for quiet solar conditions.

Description: Orthostatic intolerance is common when astronauts return to Earth: after brief spaceflight, up to two-thirds are unable to remain standing for 10 min. Previous research suggests that susceptible individuals are unable to increase their systemic vascular resistance and plasma noradrenaline concentrations above pre-flight upright levels. In this study, we tested the hypothesis that adaptation to the microgravity of space impairs sympathetic neural responses to upright posture on Earth. We studied six astronauts approximately 72 and 23 days before and on landing day after the 16 day Neurolab space shuttle mission. We measured heart rate, arterial pressure and cardiac output, and calculated stroke volume and total peripheral resistance, during supine rest and 10 min of 60 deg upright tilt. Muscle sympathetic nerve activity was recorded in five subjects, as a direct measure of sympathetic nervous system responses. As in previous studies, mean (+/- S.E.M.) stroke volume was lower (46 +/- 5 vs. 76 +/- 3 ml, P = 0.017) and heart rate was higher (93 +/- 1 vs. 74 +/- 4 beats min(-1), P = 0.002) during tilt after spaceflight than before spaceflight. Total peripheral resistance during tilt post flight was higher in some, but not all astronauts (1674 +/- 256 vs. 1372 +/- 62 dynes s cm(-5), P = 0.32). No crew member exhibited orthostatic hypotension or presyncopal symptoms during the 10 min of postflight tilting. Muscle sympathetic nerve activity was higher post flight in all subjects, in supine (27 +/- 4 vs. 17 +/- 2 bursts min(-1), P = 0.04) and tilted (46 +/- 4 vs. 38 +/- 3 bursts min(-1), P = 0.01) positions. A strong (r(2) = 0.91-1.00) linear correlation between left ventricular stroke volume and muscle sympathetic nerve activity suggested that sympathetic responses were appropriate for the haemodynamic challenge of upright tilt and were unaffected by spaceflight. We conclude that after 16 days of spaceflight, muscle sympathetic nerve responses to upright tilt are normal.

Description: After four decades of human exploration in space, many scientists consider the medical consequences from radiation exposures to be the major biological risk associated with long-term missions. This conclusion is based upon results from a research program that has evolved over the past thirty years. Despite the diversity in both opinions and approaches that necessarily arise in research endeavors such as this, a commonality has emerged from our community. We need epidemiological data for humans, animal data in areas where no human data exist, and data on mechanisms to get from animal to humans. We need a programmatic infrastructure that addresses specific goals as well as basic research. These concepts might be deemed overly simplistic and even tautologous were it not for the fact that they are frequently underutilized and even ignored. This article examines the goals, premises, and infrastructures proposed by expert panels and agencies to address radiation risks in space. It is proposed that the required level of effort and the resources available demand a unified, focused international effort that is, at the same time, subjected to rigorous peer review if it is to be successful. There is a plan; let us implement it.

Description: For many years it has been suggested that lava tubes on the Moon could provide an ideal location for a manned lunar base, by providing shelter from various natural hazards, such as cosmic radiation, meteorites, micrometeoroids, and impact crater ejecta, and also providing a natural environmental control, with a nearly constant temperature, unlike that of the lunar surface showing extreme variation in its diurnal cycle. An analysis of radiation safety issues on lunar lava tubes has been performed by considering radiation from galactic cosmic rays (GCR) and Solar Particle Events (SPE) interacting with the lunar surface, modeled as a regolith layer and rock. The chemical composition has been chosen as typical of the lunar regions where the largest number of lava tube candidates are found. Particles have been transported all through the regolith and the rock, and received particles flux and doses have been calculated. The radiation safety of lunar lava tubes environments has been demonstrated.

Description: The NCRP has recently defined RBE values and a new quantity (Gy-Eq) for use in estimation of deterministic effects in space shielding and operations. The NCRP's RBE for neutrons is left ambiguous and not fully defined. In the present report we will suggest a complete definition of neutron RBE consistent with the NCRP recommendations and evaluate attenuation properties of deterministic effects (Gy-Eq) in comparison with other dosimetric quantities.

Description: Early space radiation shield code development relied on Monte Carlo methods and made important contributions to the space program. Monte Carlo methods have resorted to restricted one-dimensional problems leading to imperfect representation of appropriate boundary conditions. Even so, intensive computational requirements resulted and shield evaluation was made near the end of the design process. Resolving shielding issues usually had a negative impact on the design. Improved spacecraft shield design requires early entry of radiation constraints into the design process to maximize performance and minimize costs. As a result, we have been investigating high-speed computational procedures to allow shield analysis from the preliminary concept to the final design. For the last few decades, we have pursued deterministic solutions of the Boltzmann equation allowing field mapping within the International Space Station (ISS) in tens of minutes using standard Finite Element Method (FEM) geometry common to engineering design methods. A single ray trace in such geometry requires 14 milliseconds and limits application of Monte Carlo methods to such engineering models. A potential means of improving the Monte Carlo efficiency in coupling to spacecraft geometry is given.

Description: The National Council on Radiation Protection and Measurements (NCRP) has recently published a report (Report #137) that discusses various aspects of the concepts used in radiation protection and the difficulties in measuring the radiation environment in spacecraft for the estimation of radiation risk to space travelers. Two novel dosimetric methodologies, fluence-based and microdosimetric event-based methods, are discussed and evaluated, along with the more conventional quality factor/LET method. It was concluded that for the present, any reason to switch to a new methodology is not compelling. It is suggested that because of certain drawbacks in the presently-used conventional method, these alternative methodologies should be kept in mind. As new data become available and dosimetric techniques become more refined, the question should be revisited and that in the future, significant improvement might be realized. In addition, such concepts as equivalent dose and organ dose equivalent are discussed and various problems regarding the measurement/estimation of these quantities are presented.

Description: The paper presents a theoretical model for the response of a tissue-equivalent proportional counter (TEPC) irradiated with charged particles. Heavy ions and iron ions in particular constitute a significant part of radiation in space. TEPCs are used for all space shuttle and International Space Station (ISS) missions to estimate the dose and radiation quality (in terms of lineal energy) inside spacecraft. The response of the tissue-equivalent proportional counters shows distortions at the wall/cavity interface. In this paper, we present microdosimetric investigation using Monte Carlo track structure calculations to simulate the response of a TEPC to charged particles of various LET (1 MeV protons, 2.4 MeV alpha particles, 46 MeV/nucleon 20Ne, 55 MeV/nucleon 20Ne, 45 MeV/nucleon 40Ar, and 1.05 GeV/nucleon 56Fe). Data are presented for energy lost and energy absorbed in the counter cavity and wall. The model calculations are in good agreement with the results of Rademacher et al. (Radiat. Res. 149, 387-389, 1998), including the study of the interface between the wall and the sensitive region of the counter. It is shown that the anomalous response observed at large event sizes in the experiment is due to an enhanced entry of secondary electrons from the wall into the gas cavity.

Description: Since its inception at the National Aeronautics and Space Administration (NASA) Ames Research Center in the mid-1970s, many laboratories around the world have used the rat hindlimb unloading model to simulate weightlessness and to study various aspects of musculoskeletal loading. In this model, the hindlimbs of rodents are elevated to produce a 30 degrees head-down tilt, which results in a cephalad fluid shift and avoids weightbearing by the hindquarters. Although several reviews have described scientific results obtained with this model, this is the first review to focus on the technical aspects of hindlimb unloading. This review includes a history of the technique, a brief comparison with spaceflight data, technical details, extension of the model to mice, and other important technical considerations (e.g., housing, room temperature, unloading angle, the potential need for multiple control groups, age, body weight, the use of the forelimb tissues as internal controls, and when to remove animals from experiments). This paper is intended as a reference for researchers, reviewers of manuscripts, and institutional animal care and use committees. Over 800 references, related to the hindlimb unloading model, can be accessed via the electronic version of this article.

Description: OBJECTIVES: We studied hemodynamic changes leading to orthostatic vasovagal presyncope to determine whether changes of cerebral artery blood flow velocity precede or follow reductions of arterial pressure. BACKGROUND: Some evidence suggests that disordered cerebral autoregulation contributes to the occurrence of orthostatic vasovagal syncope. We studied cerebral hemodynamics with transcranial Doppler recordings, and we closely examined the temporal sequence of changes of cerebral artery blood flow velocity and systemic arterial pressure in 15 patients who did or did not faint during passive 70 degrees head-up tilt. METHODS: We recorded photoplethysmographic arterial pressure, RR intervals (electrocardiogram) and middle cerebral artery blood flow velocities (mean, total, mean/RR interval; Gosling's pulsatility index; and cerebrovascular resistance [mean cerebral velocity/mean arterial pressure, MAP]). RESULTS: Eight men developed presyncope, and six men and one woman did not. Presyncopal patients reported light-headedness, diaphoresis, or a sensation of fatigue 155 s (range: 25 to 414 s) before any cerebral or systemic hemodynamic change. Average cerebral blood flow velocity (CBFV) changes (defined by an iterative linear regression algorithm) began 67 s (range: 9 to 198 s) before reductions of MAP. Cerebral and systemic hemodynamic measurements remained constant in nonsyncopal patients. CONCLUSIONS: Presyncopal symptoms and CBFV changes precede arterial pressure reductions in patients with orthostatic vasovagal syncope. Therefore, changes of cerebrovascular regulation may contribute to the occurrence of vasovagal reactions.

Description: Models of gas bubble dynamics for studying decompression sickness have been developed by considering the bubble to be immersed in an extravascular tissue with diffusion-limited gas exchange between the bubble and the surrounding unstirred tissue. In previous versions of this two-region model, the tissue volume must be theoretically infinite, which renders the model inapplicable to analysis of bubble growth in a finite-sized tissue. We herein present a new two-region model that is applicable to problems involving finite tissue volumes. By introducing radial deviations to gas tension in the diffusion region surrounding the bubble, the concentration gradient can be zero at a finite distance from the bubble, thus limiting the tissue volume that participates in bubble-tissue gas exchange. It is shown that these deviations account for the effects of heterogeneous perfusion on gas bubble dynamics, and are required for the tissue volume to be finite. The bubble growth results from a difference between the bubble gas pressure and an average gas tension in the surrounding diffusion region that explicitly depends on gas uptake and release by the bubble. For any given decompression, the diffusion region volume must stay above a certain minimum in order to sustain bubble growth.

Description: The development of orthostatic hypotension and instability immediately after return from spaceflight has been a significant operational problem to astronauts for more than four decades. Significant reductions in stroke volume and 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 reduced circulating blood volume, although cardiac atrophy might also contribute. Space flight and ground based experiments have demonstrated that an inability to provide adequate peripheral vasoconstriction in astronauts that become presyncopal may be associated with several mechanisms including reduced sympathetic nerve activity, arterial smooth muscle atrophy and/or hyporeactivity, hypersensitivity of beta-adrenergic receptors, etc. In addition, an inability to provide adequate tachycardia in presyncopal subjects may be associated with reduced carotid-cardiac baroreflex sensitivity. Based on the current knowledge and understanding of cardiovascular mechanisms that are altered during exposure to microgravity, a major focus of future research should be directed to the systematic evaluation of potential countermeasures that specifically target and restore the function of these mechanisms. Based on a preliminary systematic evaluation presented in this review, acute physical exercise designed to elicit maximal effort, G-suit inflation, artificial gravity, and specific pharmacological interventions, alone or in combination, have shown promise as successful countermeasures that provide protection against post-flight orthostatic intolerance.

Description: We measured blood erythropoietin (EPO) concentration, arterial O(2) saturation (Sa(O(2))), and urine PO(2) in 48 subjects (32 men and 16 women) at sea level and after 6 and 24 h at simulated altitudes of 1,780, 2,085, 2,454, and 2,800 m. Renal blood flow (Doppler) and Hb were determined at sea level and after 6 h at each altitude (n = 24) to calculate renal O(2) delivery. EPO increased significantly after 6 h at all altitudes and continued to increase after 24 h at 2,454 and 2,800 m, although not at 1,780 or 2,085 m. The increase in EPO varied markedly among individuals, ranging from -41 to 400% after 24 h at 2,800 m. Similar to EPO, urine PO(2) decreased after 6 h at all altitudes and returned to baseline by 24 h at the two lowest altitudes but remained decreased at the two highest altitudes. Urine PO(2) was closely related to EPO via a curvilinear relationship (r(2) = 0.99), although also with prominent individual variability. Renal blood flow remained unchanged at all altitudes. Sa(O(2)) decreased slightly after 6 h at the lowest altitudes but decreased more prominently at the highest altitudes. There were only modest, albeit statistically significant, relationships between EPO and Sa(O(2)) (r = 0.41, P 〈 0.05) and no significant relationship with renal O(2) delivery. These data suggest that 1) the altitude-induced increase in EPO is "dose" dependent: altitudes 〉 or =2,100-2,500 m appear to be a threshold for stimulating sustained EPO release in most subjects; 2) short-term acclimatization may restore renal tissue oxygenation and restrain the rise in EPO at the lowest altitudes; and 3) there is marked individual variability in the erythropoietic response to altitude that is only partially explained by "upstream" physiological factors such as those reflecting O(2) delivery to EPO-producing tissues.

Description: Exposure to altitude with or without exercise usually results in body dehydration. Psychological and physiological preparation for exercise at altitude involves consideration of maintaining body warmth in a cool to cold environment with progressively lower oxygen content (partial pressure) as altitude increases. However, this discussion will focus on altitudes below 14,000 it where supplemental breathing oxygen is not required for sojourns of healthy people. Background information and helpful advice for those who exercise in the cold can be found in selected articles in the 2001 Winter Issue of this Newsletter: M.B. Ducharme, Get ready for outdoor winter play: prepare yourself for the cold; C. O'Brien, Think layers when dressing for exercise in the cold; B.G. Rice and R. Ellis, Let it snow, let it snow, let it snow - but be aware of winter hazards; and L.B. Mayers, Exercise - induced asthma.

Description: In May 2000, senior officials of the U.S. Department of Veterans Affairs (VA) and NASA signed an agreement that would commit the two agencies to create the Patient Safety Reporting System (PSRS) to report: events or situations that could have resulted in accident, injury, or illness, but did not, either by chance or through timely intervention (close-calls); unexpected serious occurrences that involved a patient or employee's death, physical injury, or psychological injury; lessens learned; and safety ideas. The VA provided NASA with funding for the initial development of the new system, which automatically removes all personal names, facility names and locations, and other potentially identifying information before entering reports into its database. Designed to complement the VA's current internal reporting systems, the PSRS is modeled after NASA's Aviation Safety Reporting System, which was established in 1975 under a Memorandum of Agreement between the Federal Aviation Administration and NASA and began operation in 1976.

Description: Reduction and stabilization of solid wastes generated during space missions is a major concern for the Advanced Life Support - Resource Recovery program at the NASA, Kennedy Space Center. Solid wastes provide substrates for pathogen proliferation, produce strong odor, and increase storage requirements during space missions. A five periods experiment was conducted to evaluate the Space Operation Bioconverter (SOB), an in vessel composting system, as a biological processing technology to reduce and stabilize simulated long-term missions space related solid-wastes (SRSW). For all periods, SRSW were sorted into components with fast (FBD) and slow (SBD) biodegradability. Uneaten food and plastic were used as a major FBD and SBD components, respectively. Compost temperature (C), CO2 production (%), mass reduction (%), and final pH were utilized as criteria to determine compost quality. In period 1, SOB was loaded with a 55% FBD: 45% SBD mixture and was allowed to compost for 7 days. An eleven day second composting period was conducted loading the SOB with 45% pre-composted SRSW and 55% FBD. Period 3 and 4 evaluated the use of styrofoam as a bulking agent and the substitution of regular by degradable plastic on the composting characteristics of SRSW, respectively. The use of ceramic as a bulking agent and the relationship between initial FBD mass and heat production was investigated in period 5. Composting SRSW resulted in an acidic fermentation with a minor increase in compost temperature, low CO2 production, and slightly mass reduction. Addition of styrofoam as a bulking agent and substitution of regular by biodegradable plastic improved the composting characteristics of SRSW, as evidenced by higher pH, CO2 production, compost temperature and mass reduction. Ceramic as a bulking agent and increase the initial FBD mass (4.4 kg) did not improve the composting process. In summary, the SOB is a potential biological technology for reduction and stabilization of mission space-related solid wastes. However, the success of the composting process may depend of the physical characteristics (particle size, porosity, structure, texture) of the SBD components which would require pre-processing of solid wastes before placing them in the SOB.

Description: NASA's Jet Propulsion Laboratory's collaborated with LC Technologies, Inc., to improve LCT's Eyegaze Communication System, an eye tracker that enables people with severe cerebral palsy, muscular dystrophy, multiple sclerosis, strokes, brain injuries, spinal cord injuries, and ALS (amyotrophic lateral sclerosis) to communicate and control their environment using their eye movements. To operate the system, the user sits in front of the computer monitor while the camera focuses on one eye. By looking at control keys on the monitor for a fraction of a second, the user can 'talk' with speech synthesis, type, operate a telephone, access the Internet and e-mail, and run computer software. Nothing is attached to the user's head or body, and the improved size and portability allow the system to be mounted on a wheelchair. LCT and JPL are working on several other areas of improvement that have commercial add-on potential.

Description: The accuDEXA(R) Bone Mineral Density Assessment System, manufactured by Schick Technologies, Inc., utilizes "camera on a chip" sensor technology invented and developed by NASA's Jet Propulsion Laboratory. Schick's accuDEXA system offers several advantages over traditional osteoporosis tests, which assess bone density loss in the hip and spine, and require specialized personnel to conduct. With accuDEXA, physicians can test the entire body's bone density at a peripheral site, such as the finger, without applying gels or having patients remove garments. Results are achieved in 30 seconds and printed out in less than a minute, compared to the estimated exam time of 15 minutes for hip and spine density analyses. Schick has also applied the CMOS APS technology to a new software product that performs dental radiography using up to 90 percent less radiation exposure than conventional X-rays. Called Computed Dental Radiography(R), the new digital imaging product utilizes an electronic sensor in place of X-ray film to generate sharp and clear images that appear on a computer screen within 3 seconds, and can be enlarged and enhanced to identify problems.

Description: Cambridge Heart, Inc., has licensed the only U.S. Food and Drug Administration-cleared tool to identify those at risk for sudden cardiac death (SCD). The Microvolt T-Wave Alternans Test(TM) was invented by Dr. Richard J. Cohen, a professor at the Harvard-Massachusetts Institute of Technology (MIT) Division of Health Sciences and Technology, with developmental support and funding from NASA's Johnson Space Center and the National Space Biomedical Research Institute (NSBRI) in Houston, Texas. In 1993, MIT licensed the technology to Cambridge Heart, Inc., a start-up company that Dr. Cohen helped to establish. Cambridge Heart's non-invasive technology measures T-wave alternans, a change from one heartbeat to the next that is too minute to be detected by a standard electrocardiogram. Cardiac patients with such a change in heartbeat regulation are faced with a much greater risk of ventricular arrhythmia and SCD than those without it. The company's ability to measure electrical alternans on a microvolt level has been clinically proven to be just as accurate as - and in some studies, more accurate than - more costly and somewhat risky, invasive procedures, such as electrophysiological testing.

Description: A collaboration between NASA, Dr. Michael DeBakey, Dr. George Noon, and MicroMed Technology, Inc., resulted in a life-saving heart pump for patients awaiting heart transplants. The MicroMed DeBakey VAD functions as a "bridge to heart transplant" by pumping blood throughout the body to keep critically ill patients alive until a donor heart is available. Weighing less than 4 ounces and measuring 1 inch by 3 inches, the pump is approximately one-tenth the size of other currently marketed pulsatile VADs. This makes it less invasive and ideal for smaller adults and children. Because of the pump's small size, less than 5 percent of the patients implanted developed device-related infections. It can operate up to 8 hours on batteries, giving patients the mobility to do normal, everyday activities.The MicroMed DeBakey VAD is a registered trademark of MicroMed Technology, Inc.

Description: Acid beta-glucocerebrosidase (N-acylsphingosyl - O - beta-D - glucoside:glucohydrolase) is a lysosomal glycoprotein that catalyzes the hydrolysis of the glycolipid glucocerebroside to glucose and ceramide. Inadequate levels of this enzyme underly the pathophysiology of Gaucher's disease. Cerezyme(R) (Genzyme Corporation, Cambridge, MA) is a partially deglycosylated form of recombinant human acid beta-glucocerebrosidase that is commercially available for the treatment of Gaucher patients. Although acid beta-glucocerebrosidase belongs to a large family of glycosidases, relatively little is known regarding its structural biology. We report the crystallization and the initial diffraction analysis of Cerezyme(R). The crystals are C-centered orthorhombic, with unit-cell parameters of a = 285.0 A, b = 110.2 A, and c = 91.7 A. A 99.9 A complete data set has been collected to 2.75 A with an R(sub sym) of 8.8 %.

Description: Data describing long-term materials performance under exposure to space environments has accumulated gradually over the past four decades. The authors present here selected results from several previous flight experiments and operational spacecraft, and a few examples from a current flight experiment. As examples of environmental effects on materials, analysis of Gortex samples from the Passive Optical Sample Assembly II (POSA II) experiment on the MIR-Shuttle docking module will be described. Results from a previous evaluation of radiation on silverized Teflon from over ten individual satellites will be summarized. Several examples of contamination effects on materials properties will be presented. These include outgassing of solar arrays onto nearby surfaces of the POSA I experiment and contamination of certain surfaces of the Long Duration Exposure Facility (LDEF). Results from experiments with silicone contamination on satellites in geosynchronous orbit will be compared with measurements on the Solar Maximum satellite and the LDEF. A number of techniques are being attempted to extend the range of exposure conditions present on selected experiments. Use of focusing concentrators on the Effect of Space Environments on Materials (ESEM), POSA, and Materials International Space Station Experiment (MISSE) will be described. A technique for obtaining time-resolved data from a passive materials experiment will be described. The status of an on-going materials flight experiment, MISSE, will be reported. Finally, the authors will draw some conclusions about the current state of knowledge relating to materials chosen for spacecraft applications. Understanding of degradation mechanisms, state of predictive models, and the need to strengthen model inputs will be discussed.

Description: Accurate characterization of single-trial field potential responses is critical from a number of perspectives. For example, it allows differentiation of an evoked response from ongoing EEG. We previously developed the multiple component Event Related Potential (mcERP) algorithm to improve resolution of the single-trial evoked response. The mcERP model states that multiple components, each specified by a stereotypic waveform varying in latency and amplitude from trial to trial, comprise the evoked response. Application of the mcERP algorithm to simulated data with three independent, synthetic components has shown that the model is capable of separating these components and estimating their variability. Application of the model to single trial, visual evoked potentials recorded simultaneously from all V1 laminae in an awake, fixating macaque yielded local and far-field components. Certain local components estimated by the model were distributed in both granular and supragranular laminae. This suggests a linear coupling between the responses of thalamo-recipient neuronal ensembles and subsequent responses of supragranular neuronal ensembles, as predicted by the feedforward anatomy of V1. Our results indicate that the mcERP algorithm provides a valid estimation of single-trial responses. This will enable analyses that depend on trial-to-trial variations and those that require separation of the evoked response from background EEG rhythms

Description: Decreased working capacity and "orthostatic" intolerance are two major problems for astronauts during and after landing from spaceflight in a return vehicle. The purpose was to test the hypotheses that (1) supine-passive-acceleration training, supine-interval-exercise plus acceleration training, and supine exercise plus acceleration training will improve orthostatic tolerance (OT) in ambulatory men; and that (2) addition of aerobic exercise conditioning will not influence this enhanced OT from that of passive-acceleration training. Seven untrained men (24-38 yr) underwent 3 training regimens (30 min/d x 5d/wk x 3wk on the human-powered centrifuge - HPC): (a) Passive acceleration (alternating +1.0 Gz to 50% Gzmax); (b) Exercise acceleration (alternating 40% - 90% V02max leg cycle exercise plus 50% of HPCmax acceleration); and (c) Combined intermittent exercise-acceleration at 40% to 90% HPCmax. Maximal supine exercise workloads increased (P 〈 0.05) by 8.3% with Passive, by 12.6% with Exercise, and by 15.4% with Combined; but maximal V02 and HR were unchanged in all groups. Maximal endurance (time to cessation) was unchanged with Passive, but increased (P 〈 0.05) with Exercise and Combined. Resting pre-tilt HR was elevated by 12.9% (P 〈 0.05) only after Passive training, suggesting that exercise training attenuated this HR response. All resting pre-tilt blood pressures (SBP, DBP, MAP) were not different pre- vs. post-training. Post-training tilt-tolerance time and HR were increased (P 〈 0.05) only with Passive training by 37.8% and by 29.1%, respectively. Thus, addition of exercise training attenuated the increased Passive tilt tolerance. Resting (pre-tilt) and post-tilt cardiac R-R interval, stroke volume, end-diastolic volume, and cardiac output were all uniformly reduced (P 〈 0.05) while peripheral resistance was uniformly increased (P 〈 0.05) pre-and post-training for the three regimens indicating no effect of any training regimen on those cardiovascular variables. Plasma volume (% delta) was uniformly decreased by 8% to 14% (P 〈 0.05) at tilt-tolerance pre- vs. post-training for all regimens indicating no effect of these training regimens on the level of vascular fluid shifts.

Description: Present experiments were designed to quantify the alternating current (AC) component of the semicircular canal microphonic for angular motion stimulation as a function of stimulus frequency and amplitude. The oyster toadfish, Opsanus tau, was used as the experimental model. Calibrated mechanical indentation of the horizontal canal duct was used as a stimulus to generate hair-cell and afferent responses reproducing those present during head rotation. Sensitivity to polarization of the endolymph DC voltage re: perilymph was also investigated. Modulation of endolymph voltage was recorded using conventional glass electrodes and lock-in amplification over the frequency range 0.2-80 Hz. Access to the endolymph for inserting voltage recording and current passing electrodes was obtained by sectioning the anterior canal at its apex and isolating the cut ends in air. For sinusoidal stimulation below approx.10 Hz, the horizontal semicircular canal AC microphonic was nearly independent of stimulus frequency and equal to approximately 4 microV per micron indent (equivalent to approx. 1 microV per deg/s). A saturating nonlinearity decreasing the microphonic gain was present for stimuli exceeding approx.3 micron indent (approx. 12 deg/s angular velocity). The phase was not sensitive to the saturating nonlinearity. The microphonic exhibited a resonance near 30Hz consistent with basolateral current hair cell resonance observed previously in voltage-clamp records from semicircular canal hair cells. The magnitude and phase of the microphonic exhibited sensitivity to endolymphatic polarization consistent with electro-chemical reversal of hair cell transduction currents.

Description: The aims of this study were: (1) to examine the effect of three days of bed rest (BR) on basal plasma epinephrine [E] and norepinephrine [NE] and the catecholamine responses to various physiological stimuli, and (2) to find out whether previous physical activity modifies effects of BR. In the first series, 29 young men (11 sedentary students, 8 endurance and 10 strength trained athletes) were submitted to oral glucose tolerance test in supine position and to active orthostatic test before and after 3 days of BR. Plasma [E] and [NE] were measured after overnight fast (basal condition), at 60, 120 and 180 min after glucose ingestion (70 a), and at the 8th min of unsupported standing. In the second series, other 22 subjects (12 sedentary students, 10 endurance and 10 strength trained athletes) were submitted to 2 min cold pressor test (CPT) and exercise. Plasma E and NE were determined in the supine position after overnight fast and at 60th and 120th s of hand cooling. Then, after breakfast followed by 2-3 hour sitting, the subjects performed cycle ergometer exercise with workload increasing until volitional exhaustion. Plasma [E] and [NE] were determined at the end of each load. Plasma catecholamines were determined made radioenzymatically. After BR, basal plasma [NE] was decreased in endurance and strength athletes (p〈0.01) but not in sedentary subjects. In neither group BR affected the basal [E]. Responses of both catecholamines to glucose load were diminished after BR in all three groups (p〈0.05) but the effect was most pronounced in the endurance athletes. All subjects tolerated well 8-min standing although their heart rate response was increased after BR. Plasma catecholamine responses standing were not significantly affected by BR in either group but the plasma [NE] and [E] during standing were lowered after BR in endurance athletes (p〈0.01). BR did not affect blood pressure and catecholamine responses to CPT. The pre- and post-exercise plasma catecholamines were similar before and after BR although the subjects achieved lower maximal loads after BR. In endurance athletes the threshold for plasma NA rise occurred at lower work intensity after than before BR (p〈0.05).

Description: The objective of this study was to determine the accuracy of bone density measurement with a new OCT technology. A phantom was fabricated using two materials, a water-equivalent compound and hydroxyapatite (HA), combined in precise proportions (QRM GrnbH, Germany). The phantom was designed to have the approximate physical size and range in bone density as a human calcaneus, with regions of 0, 50, 100, 200, 400, and 800 mg/cc HA. The phantom was scanned at 80, 120 and 140 KVp with a GE CT/i HiSpeed Advantage scanner. A ring of highly attenuating material (polyvinyl chloride or teflon) was slipped over the phantom to alter the image by introducing non-axi-symmetric beam hardening. Images were corrected with a new OCT technology using an estimate of the effective X-ray beam spectrum to eliminate beam hardening artifacts. The algorithm computes the volume fraction of HA and water-equivalent matrix in each voxel. We found excellent agreement between expected and computed HA volume fractions. Results were insensitive to beam hardening ring material, HA concentration, and scan voltage settings. Data from all 3 voltages with a best fit linear regression are displays.

Description: Dear Dr. Bronner: I have been reading in The Physiologist the letters from senior physiologists for many years with great interest. It is impressive that many of the respondents are still pursuing scientific endeavours in their 70's and some even in their 80's. The interesting task is to ponder the relative causative proportions of heredity and environment responsible. One wonders whether knowing something about physiology engenders longer and more productive lives? I suspect so because of the accompanying self-discipline. But another factor would seem to be the pervasive joy of working in this profession. I have been fortunate to be able to acquire the joy of physiology during my graduate studies at Illinois, and to have been able to carry it over here at NASA, Ames Research Center for the past 40 years. A truly academic style research environment at a federal research center is rare. The trick to a joyous research career is to overcome those ever-present slings and arrows of outrageous fortune with dignity whenever possible. To that end I have found solace and guidance in reading the history of warfare and its leaders, especially Sun Tsu's The Art of War and Clauswitz's On War. I became eligible for retirement in 1993, but to insure domestic tranquility and also the joy of pursuing my research hobby have continued working in the laboratory on human research. It is troubling to see that funding for individual scientists conducting human research is declining rapidly, along with their new ideas; perhaps the old ones are more comfortable. Hopefully I can provide a similar response when I'm 80! Thanks for your interest. Sincerely, John Greenleaf

Description: The recently commercialized multiplex fluorescence in situ hybridization (m-FISH) technique, which allows human chromosomes to be painted in 24 different colors, was used to analyze chromosome aberrations in diploid human fibroblast cells after in vitro radiation exposure. Confluent flasks of a normal primary fibroblast cell line (AG 1522) were irradiated at high dose rates with either gamma rays or 200 MeV/nucleon Fe ions (LET = 440 keV/micron), incubated at 37 C for 24 hours after exposure, and subsequently subcultured. A chemically induced premature chromosome condensation technique was used to collect chromosome samples 32 hours after subculture. Results showed that the fraction of exchanges which were identified as complex, i.e. involving misrejoining of three or more DSB, were higher in the Fe-irradiated samples compared with the gamma-irradiated samples, as has been shown previously using FISH with one or two painted chromosomes . The ratios of complex/simple type exchanges were similar for samples irradiated with 0.7 Gy and 3 Gy of Fe ions, although exchanges involving five or more breaks were found only in 3 Gy irradiated samples. The fraction of incomplete exchanges was also higher in Fe- than gamma-irradiated samples. Data on the distribution of individual chromosome involvement in interchromosomal exchanges will be presented.

Description: Russian investigators have reported changes in pursuit tracking of a vertically moving point stimulus during space flight. Early in microgravity, changes were manifested by decreased eye movement amplitude (undershooting) and the appearance of correction saccades. As the flight progressed, pursuit of the moving point stimulus deteriorated while associated saccadic movements were unchanged. Immediately postflight there was an improved execution of active head movements indicating that the deficiencies in pursuit function noted in microgravity may be of central origin. In contrast, tests of two cosmonauts showed that horizontal and vertical smooth pursuit were unchanged inflight. However, results of corresponding saccadic tasks showed a tendency toward the overshooting of a horizontal target early inflight with high accuracy developing later inflight, accompanied by an increased saccade velocity and a trend toward decreased saccade latency. Based on these equivocal results, we have further investigated the effects of space flight on the smooth pursuit mechanism during and after short duration flight, and postflight on returning MIR crewmembers. Sinusoidal target movement was presented horizontally at frequencies of 0.33 and 1.0 Hz. Subjects were asked to perform two trials for each stimulus combination: (1) moving eyes-only (EO) and (2) moving eyes and head (EH) with the target motion. Peak amplitude was 30 deg for 0.33 Hz trials and 15 deg for the 1.0 Hz trials. The relationship between saccade amplitude and peak velocity were plotted as a main sequence for each phase of flight, and linear regression analysis allowed us to determine the slope of each main sequence plot. The linear slopes were then combined for each flight phase for each individual subject. The main sequence for both EO and EH trials at both the 0.33 and 1.0 Hz frequencies during flight for the short duration flyers showed a reduction in saccade velocity and amplitude when compared to the preflight main sequence . This difference in the regression slopes between flight phase, head/eye condition (EO or EH), and pursuit target frequency was observed across all subjects (statistically significant at the p〈0.02, df= 2). It is interesting to note that postflight for the short duration flyers there was an immediate recovery to the preflight main sequence across all trials. There were no significant differences observed between the preflight slopes for either head movement condition (EO vs. EH). When the immediate postflight (R+O) regression slopes were compared with the preflight slopes, there was a tendency (not significant) for both saccade amplitude and peak velocity to increase during the postflight testing. This tendency had vanished by R+ 1. Of particular interest was the redistribution of saccades during the latter stages of the flight and immediately postflight in the EO condition. At the 1.0 Hz frequency the saccades tended to be clustered near the lowest target velocity. It was also interesting to note that gaze performance (eye in skull + head in space) was consistently better during the EH condition; a finding also observed by our Russian colleagues. As the results of the long duration flight become available we expect that they will not only show that postflight effects will be similar to those observed during the short duration flights, but will also last for a greater period of time following flight. It is not clear what mechanism is responsible for the decreased peak saccadic velocity during flight unless the change is related to the control of retinal slip. For example, it is possible that saccades will tend to initially undershoot their targets by a small percentage and these saccades are then followed, if vision is available, by a small augmenting corrective saccade. It has been postulated that the functional significance of this undershooting tendency is to maintain the spatial representation of the target on the same side of the fovea (as opposedo racing across the fovea) and hence in the same cerebral hemisphere that initiated the primary saccade thus minimizing delays caused by an intra-hemispheric transfer of information . One could also speculate that with saccade velocities greater than normal, additional corrective saccades would be required to bring the target back on the fovea. A less plausible explanation of our findings could be fatigue. Yet it seems unlikely that our subjects would show lower velocities on all inflight test days while showing increased saccade velocities immediately following space flight where fatigue is usually the greatest. Finally, the redistribution effect noted late inflight is likely caused by adaptive changes. Overall, corrective saccades appeared to be used in maintaining gaze on target; reducing retinal slip and assisting space travelers in maintaining clear vision throughout the different phases of the space flight.

Description: Musculoskeletal forces generated by normal daily activity on Earth maintain the functional and structural properties of muscle and bone throughout most of one's adult life. A reduction in the level of cumulative daily loading caused by space flight, bed rest or spinal cord injury induces rapid muscle atrophy, functional changes in muscle, and bone resorption in regions subjected to the reduced loading. Bone cells in culture and bone tissue reportedly respond to a wide variety of non-mechanical and mechanical stimuli ranging, from electromagnetic fields, and hormones to small amplitude, high frequency vibrations, fluid flow, strain rate, and stress/strain magnitude. However, neither the transduction mechanism that transforms the mechanical input into a muscle or bone metabolic response nor the characteristics, of the loading history that directly or indirectly stimulates the cell is known. Identifying the factors contributing to the input stimulus will have a major impact on the design of effective countermeasures for long duration space flight. This talk will present a brief overview of current theories of bone remodeling and functional adaptation to mechanical loading. Work from our lab will be presented from the perspective of daily cumulative loading on Earth and its relationship to bone density and structure. Our objective is to use the tibia and calcaneus as model bone sites of cortical and cancellous bone adaptation, loaded daily by musculoskeletal forces in equilibrium with the ground reaction force. All materials that will be discussed are in the open scientific literature.

Description: Air passenger miles will likely double by year 2020. The altered and restrictive environment in an airliner cabin can influence hematological homeostasis in passengers and crew. Flight-related deep various thromboemboli (DVT) have been associated with at least 577 deaths on 42 of 120 airlines from 1977 to 1984 (25 deaths/million departures), whereas many such cases go unreported. However, there are four major factors that could influence formation of possible flight-induced DVT: sleeping accomodations (via sitting immobilization), travelers' medical history (via tissue injury), cabin environmental factors (via lower partial pressure of oxygen and lower relative humidity), and the more encompassing chair-rest deconditioning (C-RD) syndrome. There is ample evidence that recent injury and surgery (especially in deconditioned hospitalized patients) facilitate thrombophlebitis and formation of DVT that may be exacerbated by the immobilization of prolonged air travel. In the healthy flying population immobilization factors associated with prolonged (〉 5 hr) C-RID such as total body dehydration, hypovolemia and increased blood viscosity, and reduced various blood flow (pooling) in the legs may facilitate formation of DVT. However, data from at least four case-controlled epidemiological studies did not confirm a direct causative relationship between air travel and DART, but factors such as history of vascular thromboemboli, various insufficiency, chronic heart failure, obesity, immobile standing position, more than 3 pregnancies, infectious disease, long-distance travel, muscular trauma and violent physical effort were significantly more frequent in DVT patients than in controls. Thus, there is no clear, direct evidence yet that prolonged sitting in airliner seats, or prolonged experimental chair-rest- or bed- rest-deconditioning treatments cause deep various thromboemboli in healthy people.

Description: Predicting the occurrence of human cancer following exposure to any agent causing genetic damage is a difficult task. This is because the uncertainty of uniform exposure to the damaging agent, and the uncertainty of uniform processing of that damage within a complex set of biological variables, degrade the confidence of predicting the delayed expression of cancer as a relatively rare event within any given clinically normal individual. The radiation health research priorities for enabling long-duration human exploration of space were established in the 1996 NRC Report entitled "Radiation Hazards to Crews of Interplanetary Missions: Biological Issues and Research Strategies". This report emphasized that a 15-fold uncertainty in predicting radiation-induced cancer incidence must be reduced before NASA can commit humans to extended interplanetary missions. That report concluded that the great majority of this uncertainty is biologically based, while a minority is physically based due to uncertainties in radiation dosimetry and radiation transport codes. Since that report, the biologically based uncertainty has remained large, and the relatively small uncertainty associated with radiation dosimetry has increased due to the considerations raised by concepts of microdosimetry. In a practical sense, however, the additional uncertainties introduced by microdosimetry are encouraging since they are in a direction of lowered effective dose absorbed through infrequent interactions of any given cell with the high energy particle component of space radiation. The biological uncertainty in predicting cancer risk for space radiation derives from two primary facts. 1) One animal tumor study has been reported that includes a relevant spectrum of particle radiation energies, and that is the Harderian gland model in mice. Fact #1: Extension of cancer risk from animal models, and especially from a single study in an animal model, to humans is inherently uncertain. 2) One human database is predominantly used for assessing cancer risk caused by space radiation, and that is the Japanese atomic bomb survivors. Fact #2: The atomic-bomb-survivor database, itself a remarkable achievement, contains uncertainties. These include the actual exposure to each individual, the radiation quality of that exposure, and the fact that the exposure was to acute doses of predominantly low-LET radiation, not to chronic exposures of high-LET radiation expected on long-duration interplanetary manned missions.

Description: Cultures of Escherichia coli grown in space reached a 25% higher average final cell population than those in comparably matched ground controls (p〈0.05). However, both groups consumed the same quantity of glucose, which suggests that space flight not only stimulated bacterial growth as has been previously reported, but also resulted in a 25% more efficient utilization of the available nutrients. Supporting experiments performed in "simulated weightlessness" under clinorotation produced similar trends of increased growth and efficiency, but to a lesser extent in absolute values. These experiments resulted in increases of 12% and 9% in average final cell population (p〈0.05), while the efficiency of substrate utilization improved by 6% and 9% relative to static controls (p=0.12 and p〈0.05, respectively). In contrast, hypergravity, produced by centrifugation, predictably resulted in the opposite effect--a decrease of 33% to 40% in final cell numbers with corresponding 29% to 40% lower net growth efficiencies (p〈0.01). Collectively, these findings support the hypothesis that the increased bacterial growth observed in weightlessness is a result of reduced extracellular mass transport that occurs in the absence of sedimentation and buoyancy-driven convection, which consequently also improves substrate utilization efficiency in suspended cultures.

Description: Idiopathic orthostatic intolerance (OI) is characterized by adrenergic symptoms with standing. Changes in central sympathetic tone or in adrenoreceptor sensitivity could contribute to this syndrome. In OI patients and control subjects, we determined heart rate (HR) and systolic blood pressure (SBP) changes after incremental bolus doses of isoproterenol and phenylephrine before and during ganglionic blockade with trimethaphan. SBP decreased by 17+/-1.6 mm Hg in patients and 3.9+/-3.8 mm Hg in control subjects (P〈0.01) with trimethaphan. Patients with a larger decrease (28+/-3.8 mm Hg, n=7) in SBP with trimethaphan had greater supine SBP and supine and upright plasma norepinephrine levels than did patients with a lesser decrease (3.0+/-3.0 mm Hg, n=7) in SBP. Supine and orthostatic HRs were similar for the groups. The majority of patients had a normal HR response to isoproterenol before and during ganglionic blockade. Phenylephrine increased SBP similarly in patients and control subjects before and during blockade. Sympathetic support is increased in a subgroup of OI patients. Hyperadrenergic and nonhyperadrenergic subgroups have similar degrees of orthostatic tachycardia. Our findings suggest that the hyperadrenergic features of OI cannot be completely explained by systemic hypersensitivity of postsynaptic alpha(1)- and beta-adrenoreceptors but rather originates in enhanced sympathetic activation.