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An assessment of dead space in pulmonary ventilation of the toad Bufo schneideri.

The respiratory cycles of Rana and Bufo has been disputed in relation to flow patterns and to the respiratory dead-space of the buccal volume. A small tidal volume combined with a much larger buccal space motivated the "jet steam" model that predicts a coherent expired flow within the dorsal part of the buccal space. Some other studies indicate an extensive mixing of lung gas within the buccal volume. In Bufo schneideri, we measured arterial, end-tidal and intrapulmonary PCO(2) to evaluate dead-space by the Bohr equation. Dead-space was also estimated as: V(D)=(total ventilation-effective ventilation)/f(R), where total ventilation and f(R) were measured by pneumotachography, while effective ventilation was derived from the alveolar ventilation equation. These approaches were consistent with a dead space of 30-40% of tidal volume, which indicates a specific pathway for the expired lung gas.

Animals↗

Anisometry of space representation in neglect dyslexia.

Patients with unilateral neglect show disorders in horizontal space perception. It has been argued that these disorders may depend on a left-right relaxation of the representational medium that becomes progressively "relaxed" toward the contralesional space and progressively "compressed" toward the ipsilesional space. We tested this hypothesis in 31 right-brain-damaged patients, 17 with neglect and 14 without neglect in two different experiments. Patients were asked to read words in canonical and anisometric letter spacing. Only in neglect patients, the manipulation of letters spacing may ameliorate neglect dyslexia. These results support the idea that the abnormalities observed in typical neglect tests are due to a distorted internal representation of the outside world. In addition, the space distortion seems to depend on the degree of horizontal relaxation of the representational medium and it is unrelated to hemianopia.

Aged↗

Unilateral neglect: a theory of proprioceptive space of a stimulus as determined by the cerebellar component of motor efference copy (and is autism a special case of neglect).

Unilateral neglect is a devastating condition, which manifests as a loss of a person's spatial awareness opposite the damaged side of the brain. It challenges our conception of the seat of the soul and its explanation is at the heart of the mind-body problem. A heuristic definition of the dorsal stream of a modality is here based on the categorization of parietal networks by the cerebellar component of motor efference copy. Taking this premise, the proprioceptive space of a stimulus is established as a concept in this paper. It is proposed that unilateral neglect is typically a dysfunction of proprioceptive space of a stimulus associated with lesions of the dorsal stream. Furthermore, most experimental findings of unilateral visual neglect (and by extrapolation, other sensory modalities), can be explained by two developmental mechanisms by which the proprioceptive space of a stimulus is encoded in the parietal cortex. Its right and left hemisphere representation can be dissociated from the hemifield of presentation of perceptual information, such that the left hemifield can have a left hemisphere representation through callosal connections and likewise, the right hemifield can have a right hemifield representation. The processing of a sensory stimulus in either parietal hemisphere is dynamically determined as shown by experimental modulation of performance. A theory of historical precedence will provide a developmental background to the organization of proprioceptive space and will invoke separate models according to specified terms of engagement. A model based on the expansion and contraction of the proprioceptive space of a stimulus as a gradient across both hemispheres and modulated by concurrent proprioceptive state will be differentiated from a model that is non-graduating but competitive and lacks such modulation. In other words, the dorsal representation of a sensory stimulus in the former case is shared to a varying degree by the two parietal hemispheres, whereas in the latter case the representation of left and right aspects of the same object stimulus is strictly divided between the two hemispheres. A further hypothesis of a dorsoventral gradient of the peripheral and foveal components of proprioceptive space characterizing dorsal stream networks will predict the double dissociation revealed by experimental paradigms. It will explain why some patients show neglect only in foveal while others only in peripheral vision. The paper proposes to unify neglect, extinction and optic ataxia on the one hand, and spatial and object-based neglect on the other hand, under a singularly proficient paradigmatic structure. A binding model as described is a component theory that acknowledges how the involved pathways or transitional zones in a pathway may contribute to a differential clinical picture as one progresses from posterior to anterior parietal cortex. Finally, a brief discussion is given on how autistic subjects neglect spatial cues and the inability of a spatial cognitive transformation underlies the impairments postulated for 'a theory of mind'.

Autistic Disorder↗

Space-time interaction as an indicator of local spread during the 2001 FMD outbreak in the UK.

During the 2001 FMD outbreak in the UK, decisions on the level of implementation of control measures were supported by predictive models. Models were mainly used as macro-level tools to predict the behaviour of the disease in the whole country rather than at the local level. Here we explore the use of the magnitude and characteristics of the space-time interaction as an indicator of local spread and, indirectly, of the effectiveness of control measures aimed at reducing short-range transmission during the course of a major livestock disease epidemic. The spatiotemporal evolution patterns are described in the four main clusters that were observed during the outbreak by means of the hazard rate and space-time K-function (K(s,t)). For each local outbreak, the relative measure D(0)(s,t), derived from K(s,t), which represents the excess risk attributable to the space-time interaction was calculated for consecutive 20-day temporal windows to represent the dynamics of the space-time interaction. The dynamics of the spatiotemporal interaction were very different among the four local clusters, suggesting that the intensity of local spread, and therefore the effectiveness of control measures, markedly differed between local outbreaks. The large heterogeneity observed in the relative impact of being close in time and space to an infected premises suggests that the decision making in relation to control of the outbreak would have benefited from indicators of local spread which could be used to complement global predictive modelling results. Despite its limitations, our results suggest that the real-time analysis of the space-time interaction can be a valuable decision support tool during the course of a livestock disease epidemic.

Animals↗

Unilateral neglect is not unilateral: evidence for additional neglect of extreme right space.

Six patients with visuospatial neglect following right hemisphere lesions were given three tasks that assessed performance in areas of space ranging from extreme left to extreme right. A line bisection task required the patients to detect and bisect lines of four different lengths at seven left-right spatial locations, a number report task required the patients to name 11 two-digit numbers in a left-right array, and a tiling task required patients to place small black tiles over the black squares of a grid that stretched from 65 degrees left to 65 degrees right. Performance was compared with that of 20 age-matched controls. The patients showed the characteristic signs of left-side neglect in left space, extending to the central midline. Performance was relatively normal in centre-right space but all 6 patients showed signs of neglect of extreme right space (60 degrees to the right of the midline and beyond). We propose that neglect is best characterised as a bilateral, asymmetrical compression of experienced space in which the constriction extends further from the left than from the right but nevertheless affects both sides of space.

Aged↗

The U.S. National Research Council's views of the radiation hazards in space.

The author was the Chairman of a Task Group on the Biological Effects of Space Radiation formed as a result of discussions between NASA and the U.S. National Research Council's Committee on Space Biology and Medicine - a committee under the U.S. National Research Council's Space Studies Board. The Task Group was asked to review current knowledge on the effects of long-term exposure to radiation in space and to consider NASA radiation shielding requirements for orbital and interplanetary spacecraft. The group was charged with assessing the adequacy of NASA planning for the protection of humans from radiation in space and with making recommendations regarding needed research and/or new shielding requirements. This manuscript is a summary of the findings and recommendations of the Task Group. Beyond the protection of the Earth's atmosphere and its magnetosphere, the exposure to ionizing radiations far exceeds that on Earth. Of all the risks astronauts may face, this one is probably the most straightforward to control - by providing adequate shielding. However, because shielding adds weight, cost and complexity to space vehicles, it is important for designers to have a good quantitative understanding of the true risk and its degree of uncertainty so as not to under- or overshield spacecrafts. The extrapolations from our knowledge of ionizing radiation effects of low linear energy transfer (LET) to the risks from high-atomic-number high-energy energetic (HZE) cosmic rays are very uncertain because the necessary experiments on the effects of such particles have not been carried out and the extrapolation from low-LET to very high-LET has great uncertainties. These uncertainties were enumerated by the Task Group, and the types of experiments needed to minimize the uncertainties were described. The report found that, because of the small amounts of available time for biological research at HZE accelerators, it would take more than a decade of effort to obtain the answers to a narrow set of key questions that would facilitate reduction in risks and identification of the types of shielding needed.

Animals↗

Apparent size of an object remains uncompressed during presaccadic compression of visual space.

It is well known that compression of visual space occurs near the saccade goal when visual stimuli are briefly flashed at various locations on a visual reference just before a saccade. We investigated how presaccadic compression of visual space affected the apparent size of an object. In the first experiment, subjects were instructed to report the apparent number of multiple bars briefly presented around the time of saccade onset. The reported number of four bars began to decline at the 50 ms mark before a saccade and reached a minimum near the saccade onset. This confirms that the compression of visual space occurs just before saccades. In the second experiment, subjects judged the apparent width of a rectangle (a single element) or four bars (four elements) presented just before saccades. The apparent width of the four-bar stimulus was compressed just before saccades, but that of the rectangle stimulus was not compressed. Experiment 3 shows that the width compression of the four-bar stimulus is consistent with the width change predicted by compression of position. These findings indicate that the shape of a single object is not distorted at the saccade goal during presaccadic compression of visual space. In addition, experiment 4 indicates that the apparent width of a flashed stimulus just before saccades depends on the processing of global shape. This extends the definition of a visual object during presaccadic compression of visual space to not only a solid element but also a constellation of multiple elements. Furthermore, the results from these experiments suggest that presaccadic compression of visual space does not prevent object recognition underlying an attentional mechanism in generating saccadic eye movements.

Adult↗

Using Spacelab as a precursor of science operations for the Space Station.

For more than 15 years, Spacelab, has provided a laboratory in space for an international array of experiments, facilities, and experimenters. In addition to continuing this important work, Spacelab is now serving as a crucial stepping-stone to the improved science, improved operations, and rapid access to space that will characterize International Space Station. In the Space Station era, science operations will depend primarily on distributed/remote operations that will allow investigators to direct science activities from their universities, facilities, or home bases. Spacelab missions are a crucial part of preparing for these activities, having been used to test, prove, and refine remote operations over several missions. The knowledge gained from preparing these Missions is also playing a crucial role in reducing the time required to put an experiment into orbit, from revolutionizing the processes involved to testing the hardware needed for these more advanced operations. This paper discusses the role of the Spacelab program and the NASA Marshall Space Flight Center- (MSFC-) managed missions in developing and refining remote operations, new hardware and facilities for use on Space Station, and procedures that dramatically reduce preparation time for flight.

Equipment Design↗

Structured methods for identifying and correcting potential human errors in space operations.

Human performance plays a significant role in the development and operation of any complex system, and human errors are significant contributors to degraded performance, incidents, and accidents for technologies as diverse as medical systems, commercial aircraft, offshore oil platforms, nuclear power plants, and space systems. To date, serious accidents attributed to human error have fortunately been rare in space operations. However, as flight rates go up and the duration of space missions increases, the accident rate could increase unless proactive action is taken to identity and correct potential human errors in space operations. The Idaho National Engineering and Environmental Laboratory (INEEL) has developed and applied structured methods of human error analysis to identify potential human errors, assess their effects on system performance, and develop strategies to prevent the errors or mitigate their consequences. These methods are being applied in NASA-sponsored programs to the domain of commercial aviation, focusing on airplane maintenance and air traffic management. The application of human error analysis to space operations could contribute to minimize the risks associated with human error in the design and operation of future space systems.

Accidents, Aviation↗

Neuronal plasticity: adaptation and readaptation to the environment of space.

While there have been few documented permanent neurological changes resulting from space travel, there is a growing literature which suggests that neural plasticity sometimes occurs within peripheral and central vestibular pathways during and following spaceflight. This plasticity probably has adaptive value within the context of the space environment, but it can be maladaptive upon return to the terrestrial environment. Fortunately, the maladaptive responses resulting from neuronal plasticity diminish following return to earth. However, the literature suggests that the longer the space travel, the more difficult the readaptation. With the possibility of extended space voyages and extended stays on board the international space station, it seems worthwhile to review examples of plastic vestibular responses and changes in the underlying neural substrates. Studies and facilities needed for space station investigation of plastic changes in the neural substrates are suggested.

Adaptation, Physiological↗

Space radiation dosimetry in low-Earth orbit and beyond.

Space radiation dosimetry presents one of the greatest challenges in the discipline of radiation protection. This is a result of both the highly complex nature of the radiation fields encountered in low-Earth orbit (LEO) and interplanetary space and of the constraints imposed by spaceflight on instrument design. This paper reviews the sources and composition of the space radiation environment in LEO as well as beyond the Earth's magnetosphere. A review of much of the dosimetric data that have been gathered over the last four decades of human space flight is presented. The different factors affecting the radiation exposures of astronauts and cosmonauts aboard the International Space Station (ISS) are emphasized. Measurements made aboard the Mir Orbital Station have highlighted the importance of both secondary particle production within the structure of spacecraft and the effect of shielding on both crew dose and dose equivalent. Roughly half the dose on ISS is expected to come from trapped protons and half from galactic cosmic rays (GCRs). The dearth of neutron measurements aboard LEO spacecraft and the difficulty inherent in making such measurements have led to large uncertainties in estimates of the neutron contribution to total dose equivalent. Except for a limited number of measurements made aboard the Apollo lunar missions, no crew dosimetry has been conducted beyond the Earth's magnetosphere. At the present time we are forced to rely on model-based estimates of crew dose and dose equivalent when planning for interplanetary missions, such as a mission to Mars. While space crews in LEO are unlikely to exceed the exposure limits recommended by such groups as the NCRP, dose equivalents of the same order as the recommended limits are likely over the course of a human mission to Mars.

Cosmic Radiation↗

Manifesto of space medicine: the next dermatologic frontier.

As the fields of astronomy, cosmology, and space travel move rapidly forward, so must space medicine. The manned space program and medical knowledge and support have developed in tandem. Dermatology will play a fundamental role in survival during space flight. This paper reviews past, present, and future accomplishments of the space program as they relate to medicine and characterizes some of dermatology's multiple roles in the future. It further explores the immunologic alterations noted during space flight and the attendant implications for health and well-being both in flight and on return to Earth, or to an Earthlike environment.

Aerospace Medicine↗

The SOS-LUX-LAC-FLUORO-Toxicity-test on the International Space Station (ISS).

In the 21st century, an increasing number of astronauts will visit the International Space Station (ISS) for prolonged times. Therefore it is of utmost importance to provide necessary basic knowledge concerning risks to their health and their ability to work on the station and during extravehicular activities (EVA) in free space. It is the aim of one experiment of the German project TRIPLE-LUX (to be flown on the ISS) to provide an estimation of health risk resulting from exposure of the astronauts to the radiation in space inside the station as well as during extravehicular activities on one hand, and of exposure of astronauts to unavoidable or as yet unknown ISS-environmental genotoxic substances on the other. The project will (i) provide increased knowledge of the biological action of space radiation and enzymatic repair of DNA damage, (ii) uncover cellular mechanisms of synergistic interaction of microgravity and space radiation and (iii) examine the space craft milieu with highly specific biosensors. For these investigations, the bacterial biosensor SOS-LUX-LAC-FLUORO-Toxicity-test will be used, combining the SOS-LUX-Test invented at DLR Germany (Patent) with the commercially available LAC-FLUORO-Test. The SOS-LUX-Test comprises genetically modified bacteria transformed with the pBR322-derived plasmid pPLS-1. This plasmid carries the promoterless lux operon of Photobacterium leiognathi as a reporter element under control of the DNA-damage dependent SOS promoter of ColD as sensor element. This system reacts to radiation and other agents that induce DNA damages with a dose dependent measurable emission of bioluminescence of the transformed bacteria. The analogous LAC-FLUORO-Test has been developed for the detection of cellular responses to cytotoxins. It is based on the constitutive expression of green fluorescent protein (GFP) mediated by the bacterial protein expression vector pGFPuv (Clontech, Palo Alto, USA). In response to cytotoxic agents, this system reacts with a dose-dependent reduction of GFP-fluorescence. Currently, a fully automated miniaturized hardware system for the bacterial set up, which includes measurements of luminescence and fluorescence or absorption and the image analysis based evaluation is under development. During the first mission of the SOS-LUX-LAC-FLUORO-Toxicity-Test on the ISS, a standardized, DNA-damaging radiation source still to be determined will be used as a genotoxic inducer. A panel of recombinant Salmonella typhimurium strains carrying either the SOS-LUX plasmid or the fluorescence-mediating lac-GFPuv plasmid will be used to determine in parallel on one microplate the genotoxic and the cytotoxic action of the applied radiation in combination with microgravity. Either in addition to or in place of the fluorometric measurements of the cytotoxic agents, photometric measurements will simultaneously monitor cell growth, giving additional data on survival of the cells. The obtained data will be available on line during the TRIPLE-LUX mission time. Though it is the main goal during the TRIPLE-LUX mission to measure the radiation effect in microgravity, the SOS-LUX-LAC-FLUORO-Toxicity-test in principle is also applicable as a biomonitor for the detection and measurement of genotoxic substances in air or in the (recycled) water system on the ISS or on earth in general.

Cosmic Radiation↗

Effects of space flight on surface marker expression.

Space flight has been shown to affect expression of several cell surface markers. These markers play important roles in regulation of immune responses, including CD4 and CD8. The studies have involved flight of experimental animals and humans followed by analysis of tissue samples (blood in humans, rats and monkeys, spleen, thymus, lymph nodes and bone marrow in rodents). The degree and direction of the changes induced by space flight have been determined by the conditions of the flight. Also, there may be compartmentalization of the response of surface markers to space flight, with differences in the response of cells isolated from blood and local immune tissue. The same type of compartmentalization was also observed with cell adhesion molecules (integrins). In this case, the expression of integrins from lymph node cells differed from that of splenocytes isolated from rats immediately after space flight. Cell culture studies have indicated that there may be an inhibition in conversion of a precursor cell line to cells exhibiting mature macrophage characteristics after space flight, however, these experiments were limited as a result of technical difficulties. In general, it is clear that space flight results in alterations of cell surface markers. The biological significance of these changes remains to be established.

Animals↗

Effects of space flight and IGF-1 on immune function.

We tested the hypothesis that insulin-like growth factor-1 (IGF-1) would ameliorate space flight-induced effects on the immune system. Twelve male, Sprague-Dawley rats, surgically implanted with mini osmotic pumps, were subjected to space flight for 10 days on STS-77. Six rats received 10 mg/kg/day of IGF-1 and 6 rats received saline. Flight animals had a lymphocytopenia and granulocytosis which were reversed by IGF-1. Flight animals had significantly higher corticosterone levels than ground controls but IGF-1 did not impact this stress hormone. Therefore, the reversed granulocytosis did not correlate with serum corticosterone. Space flight and IGF-1 also combined to induce a monocytopenia that was not evident in ground control animals treated with IGF-1 or in animals subjected to space flight but given physiological saline. There was a significant increase in spleen weights in vivarium animals treated with IGF-1, however, this change did not occur in flight animals. We observed reduced agonist-induced lymph node cell proliferation by cells from flight animals compared to ground controls. The reduced proliferation was not augmented by IGF-1 treatment. There was enhanced secretion of TNF, IL-6 and NO by flight-animal peritoneal macrophages compared to vivarium controls, however, O2(-) secretion was not affected. These data suggest that IGF-1 can ameliorate some of the effects of space flight but that space flight can also impact the normal response to IGF-1. Grant Numbers: NAGW-1197, NAGW-2328.

Animals↗

Effect of ion implantation of TMA archwires on the rate of orthodontic sliding space closure.

A split-mouth randomized clinical trial was used to determine whether ion implantation of beta-titanium archwire would facilitate sliding space closure. After bilateral maxillary first premolar extractions, 0.19 x 0.025-inch beta-titanium arch wires, ion-implanted on one half only, were placed in 30 subjects aged 10 to 42 years wearing unimplanted 0.022 inch slot appliances. Nickel-titanium springs (150 g) were placed bilaterally to close the extraction spaces. Space closure was measured intraorally at monthly intervals until either the space on one side closed or 6 months had elapsed. The median rates of space closure were not significantly different between the ion-implanted and the unimplanted sides. The average rate of space closure on these beta-titanium wires, with or without ion implantation, was similar to the rate reported on stainless steel arch wires.

Adolescent↗

Immune function during space flight.

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.

Aerospace Medicine↗

Analysis of deletion mutations of the rpsL gene in the yeast Saccharomyces cerevisiae detected after long-term flight on the Russian space station Mir.

Using the yeast Saccharomyces cerevisiae on board the Russian space station Mir, we studied the effects of long-term space flight on mutation of the bacterial ribosomal protein L gene (rpsL) cloned in a yeast-Escherichia coli shuttle vector. The mutation frequencies of the cloned rpsL gene on the Mir and the ground (control) yeast samples were estimated by transformation of E. coli with the plasmid DNAs recovered from yeast and by assessment of the conversion of the rpsL wild-type phenotype (Sm(S)) to its mutant phenotype (Sm(R)). After a 40-day space flight, some part of space samples gave mutation frequencies two to three times higher than those of the ground samples. Nucleotide sequence analysis showed no apparent difference in point mutation rates between the space and the ground mutant samples. However, the greater part of the Mir mutant samples were found to have a total or large deletion in the rpsL sequence, suggesting that space radiation containing high-linear energy transfer (LET) might have caused deletion-type mutations.

Base Sequence↗