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Estimating membrane voltage correlations from extracellular spike trains.

The cross-correlation coefficient between neural spike trains is a commonly used tool in the study of neural interactions. Two well-known complications that arise in its interpretation are 1) modulations in the correlation coefficient may result solely from changes in the mean firing rate of the cells and 2) the mean firing rates of the neurons impose upper and lower bounds on the correlation coefficient whose absolute values differ by an order of magnitude or more. Here, we propose a model-based approach to the interpretation of spike train correlations that circumvents these problems. The basic idea of our proposal is to estimate the cross-correlation coefficient between the membrane voltages of two cells from their extracellular spike trains and use the resulting value as the degree of correlation (or association) of neural activity. This is done in the context of a model that assumes the membrane voltages of the cells have a joint normal distribution and spikes are generated by a simple thresholding operation. We show that, under these assumptions, the estimation of the correlation coefficient between the membrane voltages reduces to the calculation of a tetrachoric correlation coefficient (a measure of association in nominal data introduced by Karl Pearson) on a contingency table calculated from the spike data. Simulations of conductance-based leaky integrate-and-fire neurons indicate that, despite its simplicity, the technique yields very good estimates of the intracellular membrane voltage correlation from the extracellular spike trains in biologically realistic models.

Action Potentials↗

High fidelity medical simulation in the difficult environment of a helicopter: feasibility, self-efficacy and cost.

BACKGROUND: This study assessed the feasibility, self-efficacy and cost of providing a high fidelity medical simulation experience in the difficult environment of an air ambulance helicopter. METHODS: Seven of 12 EM residents in their first postgraduate year participated in an EMS flight simulation as the flight physician. The simulation used the Laerdal SimMantrade mark to present a cardiac and a trauma case in an EMS helicopter while running at flight idle. Before and after the simulation, subjects completed visual analog scales and a semi-structured interview to measure their self-efficacy, i.e. comfort with their ability to treat patients in the helicopter, and recognition of obstacles to care in the helicopter environment. After all 12 residents had completed their first non-simulated flight as the flight physician; they were surveyed about self-assessed comfort and perceived value of the simulation. Continuous data were compared between pre- and post-simulation using a paired samples t-test, and between residents participating in the simulation and those who did not using an independent samples t-test. Categorical data were compared using Fisher's exact test. Cost data for the simulation experience were estimated by the investigators. RESULTS: The simulations functioned correctly 5 out of 7 times; suggesting some refinement is necessary. Cost data indicated a monetary cost of 440 dollars and a time cost of 22 hours of skilled instructor time. The simulation and non-simulation groups were similar in their demographics and pre-hospital experiences. The simulation did not improve residents' self-assessed comfort prior to their first flight (p > 0.234), but did improve understanding of the obstacles to patient care in the helicopter (p = 0.029). Every resident undertaking the simulation agreed it was educational and it should be included in their training. Qualitative data suggested residents would benefit from high fidelity simulation in other environments, including ground transport and for running codes in hospital. CONCLUSION: It is feasible to provide a high fidelity medical simulation experience in the difficult environment of the air ambulance helicopter, although further experience is necessary to eliminate practical problems. Simulation improves recognition of the challenges present and provides an important opportunity for training in challenging environments. However, use of simulation technology is expensive both in terms of monetary outlay and of personnel involvement. The benefits of this technology must be weighed against the cost for each institution.

Adult↗

Analysis of role-play in medical communication training using a theatrical device the fourth wall.

BACKGROUND: Communication training is a central part of medical education. The aim of this article is to explore the positions and didactic functions of the fourth wall in medical communication training, using a role-play model basically similar to a theatrical performance. METHOD: The empirical data stem from a communication training model demonstrated at an international workshop for medical teachers and course organizers. The model involves an actress playing a patient, students alternating in the role of the doctor, and a teacher who moderates. The workshop was videotaped and analyzed qualitatively. RESULTS: The analysis of the empirical material revealed three main locations of the fourth wall as it moved and changed qualities during the learning session: 1) A traditional theatre location, where the wall was transparent for the audience, but opaque for the participants in the fiction. 2) A "timeout/reflection" location, where the wall was doubly opaque, for the patient on the one side and the moderator, the doctor and the audience on the other side and 3) an "interviewing the character" location where the wall enclosed everybody in the room. All three locations may contribute to the learning process. CONCLUSION: The theatrical concept 'the fourth wall' may present an additional tool for new understanding of fiction based communication training. Increased understanding of such an activity may help medical teachers/course organizers in planning and evaluating communication training courses.

Adult↗

Bow-tie effect: differential operator.

We propose to use a differential operator for representing the influence of phase-only filters on the defocused modulation transfer function of the clear pupil aperture. We present a phase-only filter that implements optically Taylor's theorem in phase space. We show numerical simulations of the modulation transfer functions and the images that can be obtained by using the proposed filter.

Journal Article↗

The response of a spherical tissue-equivalent proportional counter to iron particles from 200-1000 MeV/nucleon.

The radiation environment on board the space shuttle and the International Space Station includes high-Z and high-energy (HZE) particles that are part of the galactic cosmic radiation (GCR) spectrum. Iron-56 particles are considered to be one of the most biologically important parts of the GCR spectrum. Tissue-equivalent proportional counters (TEPCs) are used as active dosimeters on manned space flights. These TEPCs are further used to determine the average quality factor for each space mission. A TEPC simulating a 1-microm-diameter sphere of tissue was exposed as part of a particle spectrometer to (56)Fe particles at energies from 200-1000 MeV/nucleon. The response of TEPCs in terms of mean lineal energy, y(F), and dose mean lineal energy, y(D), as well as the energy deposited at different impact parameters through the detector was determined for six different incident energies of (56)Fe particles in this energy range. Calculations determined that charged-particle equilibrium was achieved for each of the six experiments. Energy depositions at different impact parameters were calculated using a radial dose distribution model, and the results were compared to experimental data.

Cosmic Radiation↗

Simulation of spike-burst generation and Ca(2+) oscillation in pancreatic beta-cells.

Based on the experimental evidence that Na(+)-Ca(2+) exchange participates in the regulation of intracellular Ca(2+) concentration in pancreatic beta-cells, we construct a mathematical model for the cyclic spike-bursts and oscillations of intracellular Ca(2+) concentration. In our model, an increase in ATP concentration by the stimulation of glucose metabolism leads to the closure of ATP-sensitive K(+) channels (K(ATP) channels) and gradual depolarization to the threshold of voltage-gated Ca(2+) channels. Spikes are generated by the alternate activation of voltage-gated Ca(2+) and K(+) channels, causing Ca(2+) entry. The accumulated Ca(2+) ions are extruded by Na(+)-Ca(2+) exchange and Ca(2+) active transport. An increase in Na(+) influx through Na(+)-Ca(2+) exchangers results in a rise in intracellular Na(+) concentration and the activation of Na(+)-K(+) active transport. The consumption of ATP during the process of Ca(2+) extrusion leads to the opening of K(ATP) channels and repolarization. The present model could reproduce the main experimental features of the spike-burst activity and Ca(2+) oscillations following changes in the extracellular glucose concentration. As the rate of ATP production increases, the spike-burst pattern changes from bursts with long silent phases to continuous spiking. Changes in the pattern of electrical activity produced by the alteration of extracellular Na(+) and K(+) concentrations and the addition of ouabain could be reproduced in the present model.

Action Potentials↗

Comparison and assessment of blood gas related quantities including base excess, the gas exchange indices, and temperature corrected pH/PO2/PCO2, as defined in approved NCCLS standard C12-A, using a computer simulation of input variables.

Blood gases and related quantities reported to clinicians have, since the earliest days, included both directly measured as well as calculated or estimated quantities. Some developed as substitutes for quantities that were or are difficult to measure routinely, others to explain relationships between older, difficult to measure quantities and newly measureable quantities, and still others attempt to better understand the physiology of the acid-base process. The net result is a plethora of acid-base and related quantities that may be reported by different blood gas systems. In an attempt to address the issue of which quantities have stood the test of usefulness over time, and further, to examine the optimum algorithm for use in quantification, the NCCLS has developed, through its consensus process, a recommended set of quantities and their quantifying algorithms. We have studied these quantities and compared them with some other recognized approaches and present our analysis in this report. The major conclusion is that among those quantities recommended, the NCCLS algorithms present the most sensible overall approach and that we would recommend their use as described so that the quantities can be most effectively applied clinically, without differences in final values occurring due solely simple algorithm differences.

Acid-Base Equilibrium↗

Stimulus dependence of the development of the zebrafish (Danio rerio) vestibular system.

It has been suggested that stimulus dependence is a general feature of all developing sensory systems. We tested this idea for the developing zebrafish vestibular system using a bioreactor the National Aeronautic and Space Agency designed to simulate microgravity for cells in culture on earth. We replaced the culture medium with aquarium water and maintained zebrafish eggs/hatchlings in the bioreactor for either 72 or 96 h postfertilization. These experimental animals displayed a swimming behavior that was indistinguishable from the control animals when illuminated from above. However, when illuminated from below, experimental animals swam not only dorsal surface up, but also lying on their side; they corkscrewed, swam vertical loops, and occasionally even swam upside down. When incubated in the bioreactor for 96 h, the saccular otolith was significantly smaller than normal, suggesting that otolith development was either delayed or slower than normal. When incubated in the bioreactor for 72 h, some animals were missing one or more otoliths. In contrast, control animals all had two otoliths on each side. This supports the idea that otolith development was delayed. Immediately upon removal from the bioreactor at 96 h, experimental animals showed some signs of compensatory eye rotation, but with a much less clear relationship between the orientation of the eye and the direction of gravity than the age-matched control animals. This difference was still obvious 1 day later. These results support the idea that development of the vestibular system in zebrafish is dependent on the presence of the normal stimulus the system is designed to detect.

Animals↗

Force models for needle insertion created from measured needle puncture data.

The focus of this paper is to present a force-feedback model that has been developed for the epidural needle insertion procedure. The model is based on data collected from biomaterials testing studies, and consists of separate force models for each of the tissue types relevant to the epidural needle insertion procedure. These tissue force models were generalized to create force-feedback models to drive haptic devices for needle insertion simulation.

Animals↗

A numerical identifiability test for state-space models--application to optimal experimental design.

This paper describes a mathematical tool for identifiability analysis, easily applicable to high order non-linear systems modelled in state-space and implementable in simulators with a time-discrete approach. This procedure also permits a rigorous analysis of the expected estimation errors (average and maximum) in calibration experiments. The methodology is based on the recursive numerical evaluation of the information matrix during the simulation of a calibration experiment and in the setting-up of a group of information parameters based on geometric interpretations of this matrix. As an example of the utility of the proposed test, the paper presents its application to an optimal experimental design of ASM Model No. 1 calibration, in order to estimate the maximum specific growth rate microH and the concentration of heterotrophic biomass XBH.

Biodegradation, Environmental↗

[Isokinetic concentric dynamometry of knee flexors and extensors in young male].

Objective. To investigate the effects of different moving speeds on isokinetic dynamometry of knee flexors and extensors, and to provide normative data for comparative purposes in strength evaluations. Method. Thirty healthy male were tested at 60, 180, and 240 deg/sec angular velocities using a REV9000 testing and rehabilitation system. Result. Both PT (peak torque) and PT/BW (peak torque/body weights) showed significant differences (P< 0.01, P< 0.05) between flexors and extensors, and declined significantly with increased speed (P< 0.001). Peak torque differences between dominant and nondominant knee (Di%) was 10%. TPT (time to peak torque) tended to decrease as moving speeds increased (P< 0.001). APT (angle of peak torque) were 50%-70% for quadriceps, and 32%-45% for hamstrings; H/Q (hamstrings peak torque/quadriceps peak torque) was 50%-60%; WF (work fatigue) was 65%. Conclusion. The results provided a reference for strength evaluations in space medicine and space physiology, especially under simulated weightlessness and microgravity.

Aerospace Medicine↗

Comparative efficacy of cefoperazone, cefoperazone plus sulbactam, ciprofloxacin, clindamycin, metronidazole, and penicillin G against anaerobic bacteria in an animal model.

Treatment efficacy of various antimicrobial regimens against anaerobes was studied in semipermeable chambers simulating a closed-space, locally neutropenic infection site in rabbits. Bacteroides fragilis, Bacteroides melaninogenicus, Clostridium perfringens, and Peptostreptococcus anaerobius were inoculated (at a mean of 5.3 log10 CFU/ml in prereduced pooled rabbit serum) into the chambers (one isolate per chamber) in triplicate. Antimicrobial therapy consisted of cefoperazone, cefoperazone plus sulbactam, ciprofloxacin, clindamycin, metronidazole (against the gram-negative anaerobes), or penicillin G (against the gram-positive anaerobes), beginning 4 hours after organism inoculation and continuing every 6 hours for 16 doses. With the use of anaerobic techniques for specimen acquisition, transport, and culture, quantitative bacterial findings were measured at the start of therapy and at various time points thereafter. Antibiotic concentrations were measured in blood and chamber fluid by liquid chromatography or bioassay methods. At the end of the study in vivo organisms were reduced by at least 3 log10 CFU/ml from drug-free growth control chambers by all the antimicrobial regimens tested except for cefoperazone against B. fragilis and ciprofloxacin against the three isolates tested. The addition of sulbactam to cefoperazone inhibited B. fragilis beta-lactamase activity and eradicated B. fragilis in vivo. In vivo results with this model confirmed in vitro susceptibilities of all tested antimicrobials except ciprofloxacin and should provide useful indications of the potential clinical efficacy of other new agents against anaerobes.

Animals↗

Response of the seminiferous epithelium of the mouse exposed to low dose high energy (HZE) and electromagnetic radiation.

This study was undertaken to observe the response of a rapidly dividing cell population (spermatogonial) to Helium and Argon ions as compared to x-rays. Low doses (below 100 rads) were used to more nearly simulate radiation encountered during space missions. The methods used proved compatible for both light and electron microscope studies. The average relative biological effectiveness (RBE) for Helium ions is 1, while Argon is twice as effective in killing spermatogonial cells. Part of this mixed population of cells exhibits a higher sensitivity to radiation below 15 rads. Quantitation of the radiation effects by counting the necrotic cells is not feasible because of their rapid removal, therefore all measurements were done using the surviving fraction (S/So) of spermatogonial cells.

Animals↗

The optimization of technological condition in the fermentation process of glutamate by pattern recognition method.

The technological condition in the fermentation process of fermentation glutamate (such as pH value, temperature, ventilation rate, etc.) were optimized by computerized pattern recognition method. The visible optimum region may be found based on the mapping from the multi-dimensional pattern space into a plane. It is then transformed along the reciprocal direction into the original data space using Monte Carlo simulation, so the orientation of optimization and the best combination of all parameters can be determined. A new mathematical model is being proposed based on the experimental evidence in production. The transfer ratio of glucose to glutamic acid, the production capacity and the glutamic acid concentration increase 2.9%, 1.45% and 2.65% respectively by operating this optimization method. The method has been widely extended to factories and has granted in decreasing the expense of raw materials and that of the production cost.

Fermentation↗

Body volume changes during simulated microgravity. II: Comparison of horizontal and head-down bed rest.

Changes in segmental fluid volume were measured in 10 male subjects during 7 d of either horizontal (0 degrees) or antiorthostatic (-6 degrees) head-down bed rest as part of the Joint U.S./U.S.S.R. Hypokinesia Program. Impedance plethysmography (IPG) was used to measure leg, pelvic, thoracic, and arm volume changes prior to, during, and following bed rest. Results of this study demonstrate that antiorthostatic bed rest produces a larger and more persistent thoracic fluid shift than horizontal bed rest. Segmental volume responses found during this investigation are compared to those obtained during other simulated or actual space-flight experiments. Antiorthostatic thoracic volume changes from this study were found to closely approximate those estimated to take place in space while leg volume changes produced by either 0 degrees or -6 degrees bed rest were much less than those observed by others in the microgravity environment.

Adult↗

Mutation, fitness, viral diversity, and predictive markers of disease progression in a computational model of HIV type 1 infection.

The aim of this study was to develop a computational model of HIV infection able to simulate the natural history of the disease and to test predictive parameters of disease progression. We describe the results of a numerical simulation of the cellular and humoral immune response to HIV-1 infection as an adaptive pathway in a "bit-string" space. A total of 650 simulations of the HIV-1 dynamics were performed with a modified version of the Celada-Seiden immune system model. Statistics are in agreement with epidemiological studies showing a log normal distribution for the time span between infection and the development of AIDS. As predictive parameters of disease progression we found that HIV-1 accumulates "bit" mutations mainly in the peptide sequences recognized by cytotoxic CD8 T cells, indicating that cell-mediated immunity plays a major role in viral control. The viral load set point was closely correlated with the time from infection to development of AIDS. Viral divergence from the viral quasispecies that was present at the beginning of infection in long-term nonprogressors (LTNP) was found to be similar to that found in rapid progressors at the time CD4 T cells drop below the critical value of 200 cells/microl. In contrast, the diversity indicated by the number of HIV strains present at the same time was higher for rapid and normal progressors compared to LTNP, suggesting that the early immune response can make the difference. This computational model may help to define the predictive parameters of HIV dynamics and disease progression, with potential applications in therapeutic and vaccine simulations.

Biomarkers↗