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Mouse infection models for space flight immunology.

Several immunological processes can be affected by space flight. However, there is little evidence to suggest that flight-induced immunological deficits lead to illness. Therefore, one of our goals has been to define models to examine host resistance during space flight. Our working hypothesis is that space flight crews will come from a heterogeneous population; the immune response gene make-up will be quite varied. It is unknown how much the immune response gene variation contributes to the potential threat from infectious organisms, allergic responses or other long term health problems (e.g. cancer). This article details recent efforts of the Kansas State University gravitational immunology group to assess how population heterogeneity impacts host health, either in laboratory experimental situations and/or using the skeletal unloading model of space-flight stress. This paper details our use of several mouse strains with several different genotypes. In particular, mice with varying MHCII allotypes and mice on the C57BL background with different genetic defects have been particularly useful tools with which to study infections by Staphylococcus aureus, Salmonella typhimurium, Pasteurella pneumotropica and Ehrlichia chaffeensis. We propose that some of these experimental challenge models will be useful to assess the effects of space flight on host resistance to infection.

Animals↗

Chemical sensors for space applications.

There will be a great need for a wide variety of chemical analyses, both for biomedical experimentation and for the monitoring of water and air recycling processes on Space Station Freedom and later long-term space missions. The infrequent logistics flights of the Space Shuttle will necessitate onboard analysis. Chemical sensors offer several advantages over conventional analysis onboard a spacecraft. They require less crew time, space, and power. A chemical sensor consists of a selector which selectively interacts with the analyte present in a mixture of substances, and a transducer which produces an electric signal in response to the interaction of analyte and selector. The transducer signal thus provides a quantitative and selective measurement of the analyte. Types and requirements for chemical sensors to be used in biomedical experimentation and monitoring of water recycling during long-term space missions are discussed. With chemical sensors, a wide variety of analytes can be determined selectively without separation steps. In principle, chemical sensors can provide (near) real-time monitoring of many important analytes. In some cases they can even provide continuous monitoring of such analytes. The sensors, and even the ancillary instruments, are small compared to conventional analytical instruments. Their power consumption is low. Sensor measurements do not require extensive sample treatment before analysis. In most cases a sensor can simply be inserted in, or be attached to, the organism; or be placed in the water flowing through the water recycling system. Since the sensor signal can usually be provided in digitized form, rapid transmission to the ground is possible. The use of sensors thus provides an efficient use of the scarce resources of crew time, pressurized volume, and power.

Biosensing Techniques↗

Pharmacology in space: pharmacotherapy.

This chapter summarized the information available on the pharmacological kits onboard spacecraft and on the use of drugs in space, while the next chapter is dedicated to the impacts of weightlessness on drug pharmacokinetics. The need of a selected group of drugs for the use of astronauts during short-term and long-term spaceflights has been discussed. Recommendations are made for a Space Pharmacopoeia as well as for the areas of research needed to adapt medication to the weightlessness of the space environment. Although the usefulness of these drugs has been clearly demonstrated, their use also raises several problems. Physiological changes due to weightlessness may induce changes in pharmacokinetic behavior of drugs and influence their dosage regimen. Inflight data obtained by salivary drug monitoring have shown changes in the distribution of scopolamine and a significant change in the disposition of the common pain-relief agent acetaminophen taken inflight, in both drug concentration and time course. The authors of this study emphasize, however, that their data are preliminary and as yet incomplete. Further simulation studies and, if possible, inflight experiments are required. In vitro studies of the antibacterial activity of antibiotics under space conditions have shown an increased resistance of Escherichia Coli to colistin and kanamycin, and a lowered resistance of Staphylococcus Aureus to oxacillin, chloramphenicol, and erythromycin. The possible consequences of these findings for the treatment of infections contracted by astronauts are yet to be elucidated. There is still a lack of pharmacological countermeasures, particularly for preventing the progressive bone demineralization occurring in weightlessness. The treatment of space motion sickness with drugs carries with it the problem of undesirable side-effects on psychomotor performance. In order to arrive at the most appropriate medical kit for a particular mission, the best trade-off of risk versus benefit for the individual and the mission must always be attempted for any pharmacological agent.

Aerospace Medicine↗

Hindlimb unloading of growing rats: a model for predicting skeletal changes during space flight.

A model that uses hindlimb unloading of rats was developed to study the consequences of skeletal unloading and reloading as occurs during and following space flight. Studies using the model were initiated two decades ago and further developed at National Aeronautics and Space Administration (NASA)-Ames Research Center. The model mimics some aspects of exposure to microgravity by removing weightbearing loads from the hindquarters and producing a cephalic fluid shift. Unlike space flight, the forelimbs remain loaded in the model, providing a useful internal control to distinguish between the local and systemic effects of hindlimb unloading. Rats that are hindlimb unloaded by tail traction gain weight at the same rate as pairfed controls, and glucocorticoid levels are not different from controls, suggesting that systemic stress is minimal. Unloaded bones display reductions in cancellous osteoblast number, cancellous mineral apposition rate, trabecular bone volume, cortical periosteal mineralization rate, total bone mass, calcium content, and maturation of bone mineral relative to controls. Subsequent studies reveal that these changes also occur in rats exposed to space flight. In hindlimb unloaded rats, bone formation rates and masses of unloaded bones decline relative to controls, while loaded bones do not change despite a transient reduction in serum 1,25-dihydroxyvitamin D (1,25D) concentrations. Studies using the model to evaluate potential countermeasures show that 1,25D, growth hormone, dietary calcium, alendronate, and muscle stimulation modify, but do not completely correct, the suppression of bone growth caused by unloading, whereas continuous infusion of transforming growth factor-beta2 or insulin-like growth factor-1 appears to protect against some of the bone changes caused by unloading. These results emphasize the importance of local as opposed to systemic factors in the skeletal response to unloading, and reveal the pivotal role that osteoblasts play in the response to gravitational loading. The hindlimb unloading model provides a unique opportunity to evaluate in detail the physiological and cellular mechanisms of the skeletal response to weightbearing loads, and has proven to be an effective model for space flight.

Animals↗

Lessons from the space experiment SL-J/FMPT/L7: the effect of microgravity on chicken embryogenesis and bone formation.

Thirty fertilized chicken eggs preincubated for 0, 7, and 10 days on earth (10 eggs each) were flown in the space shuttle "Endeavour" and further incubated for 7 days under microgravity. Twenty out of 30 eggs (nine out of ten 10-day-old eggs; 10 out of ten 7-day-old eggs; 1 out of ten 0-day-old eggs) were recovered alive after landing. The only living embryo of the 0-day-old egg died 24 days after launch, and was comparable to a 16-day-old embryo when it died. The high mortality of the 0-day-old eggs appeared to be related to the specific inner structure of the egg. The yolk (specific gravity, 1.029) would not have separated from the albumen (1.040) during space flight. The subtle difference in specific gravity between the yolk and the albumen appeared to play a critical role in early chick embryogenesis. All the tissues, including cartilage and bone, were formed normally in 7- and 10-day-old chicken embryos during space flight. When the 7- and 10-day-old embryos recovered at Kennedy Space Center (KSC) were further incubated on earth, they hatched normally. No appreciable changes were recognized in these chicks. The reason for these unexpected results is not known. Further space experiments are needed to explain the failure of the effects of microgravity on chicken embryogenesis.

Alkaline Phosphatase↗

Color space distortions in patients with type 2 diabetes mellitus.

Color vision impairment was examined in patients with type 2 diabetes mellitus (DM2) without retinopathy. We assessed the type and degree of distortions of individual color spaces. DM2 patients (n = 32), and age-matched controls (n = 20) were tested using the Farnsworth D-15 and the Lanthony D-15d tests. In addition, subsets of caps from both tests were employed in a triadic procedure (Bimler & Kirkland, 2004). Matrices of inter-cap subjective dissimilarities were estimated from each subject's "odd-one-out" choices, and processed using non-metric multidimensional scaling. Two-dimensional color spaces, individual and group (DM2 patients; controls), were reconstructed, with the axes interpreted as the R/G and B/Y perceptual opponent systems. Compared to controls, patient results were not significant for the D-15 and D-15d. In contrast, in the triadic procedure the residual distances were significantly different compared to controls: right eye, P = 0.021, and left eye, P = 0.022. Color space configurations for the DM2 patients were compressed along the B/Y and R/G dimensions. The present findings agree with earlier studies demonstrating diffuse losses in early stages of DM2. The proposed method of testing uses color spaces to represent discrimination and provides more differentiated quantitative diagnosis, which may be interpreted as the perceptual color system affected. In addition, it enables the detection of very mild color vision impairment that is not captured by the D-15d test. Along with fundoscopy, individual color spaces may serve for monitoring early functional changes and thereby to support a treatment strategy.

Adult↗

Transfer of space technologies past and present: the Russian case.

Since the end of the 1980's transfer of government sponsored high technology space goods and services to other sectors, industry, and eventually non-government use has been a growing concern of the Russian policy makers. Today the real and functional transformation of this field is on the agenda. The paper is organized as follows. The first section analyzes the evolution of the common approach to technology transfer, looks at the main obstacles to this processes as a whole, and in the space sector in particular. The second section examines the Russian space R&D sector from the point of view of its role and place in the Russian scientific and technological base. New mechanisms of technology transfer are then considered. Here, problems of conversion, commercialization, dual-use, and internationalization are examined in the context of space technology transfer. Furthermore, issues of innovation in technology transfer are discussed. The new networks that are forming through which technologies diffuse is considered. The paper then turns to legislative and regulatory problems, including the discussion of the main principles of the Russian space transfer code, which is now being drafted. It is necessary to underline, that in the Russian case, official statistics still do not help analyze the question of technology transfer.

Government Agencies↗

Soda lime temperatures during low-flow sevoflurane anaesthesia and differences in dead-space.

BACKGROUND: Sevoflurane degrades during low-flow anaesthesia to compound A, and high carbon dioxide absorbent temperatures cause increased degradation. The purpose of this investigation was to determine if larger tidal volumes, without increasing alveolar ventilation, decrease the temperature in the carbon dioxide absorber during low- and minimal-flow sevoflurane anaesthesia. METHODS: Prospective, randomized study, including 45 patients (ASA 1-2), scheduled for elective general or urology surgery. The patients were randomly assigned to one of three treatments. Patients in group 1 (NDS) received fresh gas flow of 1 litre/min without using additional dead-space volumes. In group 2 (DS + 1.0), the patients received fresh gas flow of 1 litre/min using additional dead-space volumes, placed between the Y-piece and the HME, and patients in group 3 (DS + 0.5) received the same technique with a fresh gas flow of 0.5 litre/min. The soda lime temperatures, dead-space volumes, end-tidal carbon dioxide, sevoflurane concentrations, ventilation volumes and pressures, absorbent weight and ear temperatures were measured. RESULTS: The maximum temperature of the soda lime was 44.1 +/- 1.1 degrees C in the NDS group, 37.8 +/- 0.8 degrees C in the DS + 1.0 group and 38.5 +/- 2.7 degrees C in the DS + 0.5 group (P<0.0001). The dead-space volume between the Y-piece the tracheal tube was 164 +/- 69 ml in the DS + 1.0 group and 196 +/- 15 ml in the DS + 0.5 group (P<0.05). The ventilator pressure were higher in the DS groups compared with the NDS group (P<0.001). Soda lime weight increased in all groups. End-tidal carbon dioxide, sevoflurane concentrations and ear temperatures were similar between the groups. CONCLUSION: Increasing dead-space volumes can reduce carbon dioxide absorber temperature during low- and minimal-flow sevoflurane anaesthesia.

Aged↗

Bias toward regular form in mental shape spaces.

The distribution of figural "goodness" in 2 mental shape spaces, the space of triangles and the space of quadrilaterals, was examined. In Experiment 1, participants were asked to rate the typicality of visually presented triangles and quadrilaterals (perceptual task). In Experiment 2, participants were asked to draw triangles and quadrilaterals by hand (production task). The rated typicality of a particular shape and the probability that that shape was generated by participants were each plotted as a function of shape parameters, yielding estimates of the subjective distribution of shape goodness in shape space. Compared with neutral distributions of random shapes in the same shape spaces, these distributions showed a marked bias toward regular forms (equilateral triangles and squares). Such psychologically modal shapes apparently represent ideal forms that maximize the perceptual preference for regularity and symmetry.

Adult↗

A statistical explanation of visual space.

The subjective visual space perceived by humans does not reflect a simple transformation of objective physical space; rather, perceived space has an idiosyncratic relationship with the real world. To date, there is no consensus about either the genesis of perceived visual space or the implications of its peculiar characteristics for visually guided behavior. Here we used laser range scanning to measure the actual distances from the image plane of all unoccluded points in a series of natural scenes. We then asked whether the differences between real and apparent distances could be explained by the statistical relationship of scene geometry and the observer. We were able to predict perceived distances in a variety of circumstances from the probability distribution of physical distances. This finding lends support to the idea that the characteristics of human visual space are determined probabilistically.

Humans↗

The effect of space flight on the production of actinomycin D by Streptomyces plicatus.

The effect of space flight on production of the antibiotic actinomycin D by Streptomyces plicatus WC56452 was examined onboard the US Space Shuttle mission STS-80. Paired space flight and ground control samples were similarly prepared using identical hardware, media, and inoculum. The cultures were grown in defined and complex media under dark, anaerobic, thermally controlled (20 degrees C) conditions with samples fixed after 7 and 12 days in orbit, and viable residuals maintained through landing at 17 days, 15 h. Postflight analyses indicated that space flight had reduced the colony-forming unit (CFU) per milliliter count of S. plicatus and increased the specific productivity (pg CFU(-1)) of actinomycin D. The antibiotic compound itself was not affected, but its production time course was altered in space. Viable flight samples also maintained their sporulation ability when plated on agar medium postflight, while the residual ground controls did not sporulate.

Dactinomycin↗

[Respiratory death space and ventilation of newborn infants].

The effect of dead space reduction was studied in 10 VLBW infants (GA 26-31 wks, mean BW 1100 grms) on mechanical ventilation using a constant flow ventilator with a flow sensor device (Draeger Babylog 8000, Lubeck, Germany). Shortening of the endotracheal tube and removal of the flow sensor resulted in a calculated 50% reduction of dead space (-2.3 ml) and in a fall of tcpCO2 from (mean and range) 45 (40-49) to 35 (31-36) mmHG. This corresponds to a increase of alveolar ventilation of 22% as predicted by calculation of the dead space changes. Further attempts were made in reducing dead space ventilation by using endotracheal tubes conceived for jet ventilation, using the jet entry for the inspiratory side, or by introducing a separate continuous inspiratory flow to the tip of the endotracheal tube. Besides a routinely performed shortening of the ET tube this means of ventilation was used with success in two VLBW infants with desperate respiratory situations who both survived, in an older infant with high-grade tracheal stenosis to wean him from the respirator and in three neonates with congenital diaphragmatic hernia in conjunction with delayed operative repair who could be weaned from respiratory support 4, 13 and 20 days post surgery. We conclude that dead space reduction is a means to achieve gentle ventilation and to reduce lung damage from artificial ventilation.

Airway Resistance↗

Personal space and density as factors in task performance and feeling of crowding.

The study was an investigation of the effects of density and personal space on simple and complex task performance and on feelings of crowding on 60 female Hindu students in India. A 2 x 2 design was used. Density was manipulated by varying the number of subjects in a fixed room space (social density), and the stop-distance technique was used to measure personal space. Results revealed that complex task performance was adversely affected by a high-density condition and by the personal space of the subjects, leading to a significant interaction effect of the two variables, but no significant main or interaction effect was found for the simple task performance. The subjects with "far" personal space under the high-density condition evaluated the environment of the experimental room as most crowded, more than any other subject did.

Adolescent↗

A generalized perceptual space.

Based upon experimental results on certain visual spatial discrimination tasks, we have developed a formalism for a non-Euclidian perceptual space. In this formalism, the transformation from real to perceptual space is given by a generalized covariant tensor. The concept of parallel transport of vectors in a curved space is used to prove that closed loops in real space imply closed loops with the same orientation in the perceptual space also.

Discrimination Learning↗

Understanding and measuring powered wheelchair mobility and manoeuvrability. Part I. Reach in confined spaces.

PURPOSE: To determine: (1) what wheelchair manoeuvrability factors are important and (2) the effects of powered wheelchair design on the ability to reach in a confined space. METHOD: The relative importance of five aspects of wheelchair manoeuvrability was determined through a survey of users of wheelchairs (N = 52) and health care professionals and others (N = 89). A single young, non-disabled subject undertook repeated trials of reach distance on to a counter at the end of a corridor whose width could be adjusted by moving Styrofoam walls. RESULTS: Reaching, moving in confined spaces and avoiding collisions were more important than speed and avoiding the need to drive backwards. The rear wheel drive powered wheelchair was found to allow the greatest reach when driving backwards into the space and the wheelchair which moved in a sideways direction allowed greatest reach in the narrowest corridor. CONCLUSIONS: The survey concluded that manoeuvring in small spaces and reaching without collisions were important. The powered wheelchair with sideways capability afforded the greatest reach in confined spaces except when the rear wheel drive chair was driven in backwards. The survey respondents did not place a high priority on avoiding backwards driving but some people find this difficult to do safely.

Comprehension↗

Effect of space flight on cytokine production and other immunologic parameters of rhesus monkeys.

During a recent flight of a Russian satellite (Cosmos #2229), initial experiments examining the effects of space flight on immunologic responses of rhesus monkeys were performed to gain insight into the effect of space flight on resistance to infection. Experiments were performed on tissue samples taken from the monkeys before and immediately after flight. Additional samples were obtained approximately 1 month after flight for a postflight restraint study. Two types of experiments were carried out throughout this study. The first experiment determined the ability of leukocytes to produce interleukin-1 and to express interleukin-2 receptors. The second experiment examined the responsiveness of rhesus bone marrow cells to recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). Human reagents that cross-reacted with monkey tissue were utilized for the bulk of the studies. Results from both studies indicated that there were changes in immunologic function attributable to space flight. Interleukin-1 production and the expression of interleukin-2 receptors was decreased after space flight. Bone marrow cells from flight monkeys showed a significant decrease in their response to GM-CSF compared with the response of bone marrow cells from nonflight control monkeys. These results suggest that the rhesus monkey may be a useful surrogate for humans in future studies that examine the effect of space flight on immune response, particularly when conditions do not readily permit human study.

Animals↗

The lumbar epidural space in pregnancy: visualization by ultrasonography.

Epidural anaesthesia is an important analgesia technique for obstetric delivery. During pregnancy, however, obesity and oedema frequently obscure anatomical landmarks. Using ultrasonography, we investigated the influence of these changes on spinal and epidural anatomy. We examined 53 pregnant women who were to receive epidural block for vaginal delivery or Caesarean section. The first ultrasound imaging was performed immediately before epidural puncture; the follow-up scan was done 9 months later. The ultrasound scan of the spinal column was performed at the L3/4 interspace in transverse and longitudinal planes, using a Sonoace 6000 ultrasonograph (Kretz, Marl, Germany) equipped with a 5.0-MHz curved array probe. We measured two distances from the skin to the epidural space: the minimum (perpendicular) and the maximum (oblique) needle trajectory. The quality of ultrasonic depiction was analysed by a numerical scoring system. An average weight reduction of 12.5 kg had occurred by the follow-up examination. During pregnancy, the optimum puncture site available on the skin for epidural space cannulation was smaller, the soft-tissue channel between the spinal processes was narrower, and the skin-epidural space distance was greater. The epidural space was narrower and deformed by the tissue changes. The visibility of the ligamentum flavum, of the dura mater and of the epidural space decreased significantly during pregnancy. Nevertheless, ultrasonography offered useful pre-puncture information. Thus far, palpation has been the only available technique to facilitate epidural puncture. Ultrasound imaging enabled us to assess the structures to be perforated. We anticipate that this technique will become valuable clinically.

Adult↗

Birth spacing and child survival in rural Senegal.

BACKGROUND: Studies examining the associations between short birth spacing and child mortality have often concentrated on the strength of the associations whilst the public health importance of short spacing in specific communities has received less attention. This study re-examines the association between short birth intervals and child mortality in rural Senegal and discusses the potential direct effects of efforts to delay births on child mortality in this community. METHODS: The study uses longitudinal data in a cohort of 4852 children born between 1983 and 1989. The associations between birth spacing and child mortality are examined using logistic and Cox proportional hazards regression models. RESULTS: The probability of dying before age five is 224 per 1000 livebirths. The median interval between births is 33 months and only 12% of the birth intervals are less than 24 months in length. The odds of dying in the neonatal and post-neonatal period is 2.27 and 2.12 times higher respectively for children born after preceding birth intervals of one year or less compared to children born after longer intervals. Children born within two years of a subsequent birth are at 4.09 times higher risk of dying in the second year of life than children whose mother gave birth more than 2 years after the index birth. CONCLUSIONS: In this community where prolonged breastfeeding causes women to space their births at long intervals, short birth intervals are a consequence rather than a cause of child mortality and the potential direct effects of birth spacing efforts on child mortality are limited. To reduce the high levels of child mortality, efforts will have to be made to ensure effective preventive and curative health services, and to maintain the traditional pattern of breastfeeding.

Birth Intervals↗