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Multiple solar particle event dose time profile predictions using Bayesian inference.

The prediction of solar particle event occurrence and the resulting effects on humans and electronics continues to be a mission and/or life-threatening concern for the National Aeronautics and Space Administration and military and commercial satellite operators. While the frequency of events generally follows the solar cycle, individual event occurrence is sporadic and the prediction of resulting effects prior to the event onset is difficult. In one approach to space weather prediction, the forecaster begins to make predictions after the onset of an event. Previous work proved the efficacy of a forecasting methodology that used Bayesian inference and dose and/or dose rate information obtained early after the onset of an event to make predictions of dose and dose rate time profiles out to 120 h beyond onset. The previous work, however, was restricted to predictions for single-event solar particle events. Some of the largest recorded events, including the October 1989 and August 1972 events, were actually multiple events. In this study, we present an analysis of nine large events, some single and some multiple. This work ties together particle flux and fluence data with dose rate and dose calculations in an effort to develop a criterion for characterising an event as multiple and thus, generalising the Bayesian methodology to allow predictions for all events. Dose time profile predictions are made for the four separate events that made up the October 1989 event.

Bayes Theorem↗

The perception of moving comets at high retinal illuminance levels: a rod-cone interaction effect.

A small circular target of high retinal illuminance level can have a comet-like appearance when presented moving continuously with a speed as low as 0.2 deg/s. This perceived lengthening of the circular target increases with the speed of movement and is only observed for target presentations outside the foveal region. Data on the parametric properties of the "comet effect" are presented together with related results on the time-course of recovery of retinal sensitivity following brief exposure to intense stimuli. Measurement of target spectral irradiance levels which are just sufficient to yield the comet effect suggests that the lengthening of the circular target reflects a rod-cone interaction and therefore it may be due to unsuppressed, saturated rod responses at high retinal illuminance levels. The restriction of the comet effect to areas outside the foveal region is used to produce spatial maps of what appears to be the rod-free area of the retina. A model simulation by means of a computational approach shows that the predicted appearance of the moving target matches very closely the experimental observations on the comet effect. Model predictions based on psychophysical estimates of comet length for the stimulus conditions of these experiments yield an overall response time for the rod system of some 600 ms.

Humans↗

Electron microscope study on the hepatic sinusoidal wall and fat-storing cells in the bat.

The three cell types known to form the hepatic sinusoidal wall were electron microscopically observed in three kinds of bats captured in winter and summer. 1. The cytoplasmic extensions of sinusoidal endothelial cells consisted of continuous thicker parts ("cytoplasmic processes") and discontinuous thinner parts ("sieve plates"). The alternate disposition of the two parts was rather irregular, and the sizes, shapes and spacings of the fenestrae were variable. In the thinner parts with numerous small fenestrae, larger gaps were also mingled. The endothelium was simple-layered and devoid of basal lamina. Interendothelial junctions were found mainly between closely apposed margins of the "cytoplasmic processes" and agreed in structure with the "junctional complex" of WISSE (1970). 2. Kupffer cells, morphologically distinct from the endothelial cells, bulged strongly into the sinusoidal lumen. Provided with many microvillous pseudopods, they were stellate in appearance. They were fixed to the endothelial lining by small junctional areas which occurred between the Kupffer cell body and the "cytoplasmic processes" of the endothelium. 3. Fat-storing cells were located in the Disse's space. They generally contained only smaller amounts of lipid in a few droplets. So-called empty fat-storing cells were numerous, especially in winter bats. The perikaryonal cytoplasm revealed a large Golgi complex and well-developed granular endoplasmic reticulum. The three mesenchymal cell types of the sinusoidal wall possessed the centriole in common within the Golgi complex, but only the fat-storing cell was provided with the single cilium. Fat-storing cells extended cytoplasmic processes ramifying beneath the endothelial lining occasionally surrounding the sinusoids almost completely, and which seemed to reinforce the endothelial lining and to bring about the constriction of the sinusoid. In hypervitaminotic bats that daily received 6,000 I.U. vitamin A for three days, remarkable increase in size and number of lipid droplets was observed in slightly hypertrophic fat-storing cells, and the empty cells disappeared simulating an increased number of fat-storing cells. Suggestion was made of an antidotal function of fat-storing cells against excess vitamin A which might be considered a toxic agent in the broad sense. 4. The Disse's space of bat liver contained plasma cells, lymphocytes and macrophages, the latter too often being under migration through the endothelial fenestrae.

Animals↗

Interactions between adjacent fibers in a cardiac muscle bundle.

A strand of cardiac muscle was modeled as a small bundle of individual fibers surrounded by a large volume conductor. The bundle is a uniform assembly of small identical cylindrical fibers, arranged as a series of concentric layers, and its behavior is examined in the presence (coupled bundle) or absence (uncoupled bundle) of transverse resistive coupling between adjacent fibers. Individual fibers are continuous cables of excitable membrane, with circumferential segmentation into 12 equal patches to make the membrane potential changes dependent upon the local interstitial potential. The minimum spacing (d) between adjacent fibers is used to modify the interstitial microstructural organization and the intracellular volume fraction (fi). When d is small enough (d < 0.01 micron), fi remains unchanged at its maximum of about 90%, the interstitial potential is large, the transverse interstitial resistance is high, and the proximity effect arising from the close juxtaposition of adjacent fibers is important. A surface fiber of the uncoupled bundle exhibits little sensitivity to changes in the interstitial microstructure, owing to the dominant influence of the external volume conductor, whereas the central fiber shows a large decrease in velocity, substantial waveshape modifications, and a large increase in interstitial potential as d is reduced. In the coupled bundle, all fibers adopt the same velocity during uniform propagation, owing to the strong transverse resistive coupling; when d is reduced in the range of d < 0.01 micron, the velocity and interstitial potential changes are less pronounced than in the uncoupled bundle. When d is large enough (d > 0.01 micron), the bundle behavior (coupled and uncoupled) approaches that obtained with a bidomain formulation.

Action Potentials↗

Changes in volume, muscle compartment, and compliance of the lower extremities in man following 30 days of exposure to simulated microgravity.

The purpose of these experiments was to test the hypothesis that reduced size of the leg muscle compartment following exposure to long-duration microgravity would be associated with increased leg compliance. Eight men, 31-45 years of age, were measured for vascular compliance of the calf and serial circumferences of the thigh and calf before, during and after 30 d of continuous 6 degrees head-down bedrest. Cross-sectional areas (CSA) of muscle, fat, and bone compartments in the thigh and calf were determined pre- and post-bedrest by computed tomography. Calculated leg volumes decreased (p less than 0.05) in the calf by 9.9% and in the thigh by 4.5% from pre- to post-bedrest. Muscle compartment CSA also decreased (p less than 0.05) in both calf (-4.8%) and thigh (-8.1%); leg compliance (vol%/mm Hg x 100) increased (p less than 0.05) from 3.9 +/- 0.7 to 4.9 +/- 0.5. Calf compliance measured before and after bedrest was inversely related to calf muscle compartment CSA (r = -0.61, p less than 0.05) and the percent decrease in calf muscle compartment CSA from pre- to post-bedrest was inversely correlated with an increase in calf compliance (r = -0.72, p less than 0.05). Increased leg compliance following long-duration spaceflight is associated with reduced size of the leg muscle compartment.

Adipose Tissue↗

Dosimetric penumbra effects in catheter-based intravascular brachytherapy using a centered photon or beta line source.

Purpose: In catheter-based intravascular brachytherapy, either photon or beta emitters are often used in a linear arrangement so that blood vessels of 10-30 mm lengths can be treated. With a line source, the dose gradient in the radial direction and longitudinal direction depend on the type of radionuclides used in the treatment. The purpose of this study was to investigate the dose fall-off at the edges of a linear source in a blood vessel for different types of photon and beta emitters.Materials/Methods: Dose distributions were calculated on cylindrical blood vessels of various radii. Radioactive sources of 192Ir, 125I, 103Pd, 188Re, 32P, and 90Y/Sr were studied. All the sources were assumed to be in the form of a line. The dose rate at a point in space produced by a radioactive source was computed by integrating the point dose rate kernel of the corresponding radionuclide over the radioactive line. The point dose rate kernel was computed with Monte Carlo simulation of radiation transport. The edge effects were characterized with three newly defined quantities: longitudinal dose uniformity (LDU), effective coverage length (ECL), and margin length (ML). LDU was defined as the ratio of dose at a distance along the long axis of the vessel to the dose at center. ECL was defined as the length over which the LDU was greater than 0.95. ML was defined as half of the length difference between source length L and ECL, which is essentially the length segment at each edge that is covered by the source physical length but is being underdosed.Results: All beta emitters provided more uniform dose distributions and covered a larger portion of blood vessels longitudinally than photon emitters. Typical MLs were 2-3 mm for beta emitters and 4-6 mm for gamma emitters. As the radial depth of the point of interest increased, both the LDU and ECL decreased and ML increased. The ML increased from 2 to 3 mm for beta emitters and from 4 to 6 mm for photon emitters when the radial depth of the point of interest increased from 1.5 to 2.5 mm (typical proximal and distal media points for a 3-mm diameter lumen). The ML increased with increasing source length for all radionuclides. For beta emitters the ML increased initially from 1.5 mm to more than 2.5 mm as source length increased from 5 to 10 mm. When the source length was longer than 15 mm, the ML remains nearly constant, about 3 mm. For photon emitters, ML increased continuously from 1.5 mm to more than 6.0 mm, as source length increased from 5 to 50 mm.Conclusions: A formalism to quantify the dose uniformity along the length of a blood vessel undergoing catheter-based intravascular brachytherapy has been developed. This formalism was used to study the edge effects at the ends of several beta and photon sources. The results indicated that for a centered source the ML at each end due to penumbra effects was about 2 to 3 mm for beta emitters; about 4-6 mm for photon emitters. The ML increases as the radial depth of point of interest in the vessel increases. The ML increases also with increasing source length, especially for photon sources.

Journal Article↗

Dosimetric penumbra effects in catheter-based intravascular brachytherapy using a centered photon or beta line source.

PURPOSE: In catheter-based intravascular brachytherapy, either photon or beta emitters are often used in a linear arrangement so that blood vessels of 10-30 mm lengths can be treated. With a line source, the dose gradient in the radial direction and longitudinal direction depend on the type of radionuclides used in the treatment. The purpose of this study was to investigate the dose fall-off at the edges of a linear source in a blood vessel for different types of photon and beta emitters. MATERIALS/METHODS: Dose distributions were calculated on cylindrical blood vessels of various radii. Radioactive sources of 192Ir, 125I, 103Pd, 188Re, 32P, and 90Y/Sr were studied. All the sources were assumed to be in the form of a line. The dose rate at a point in space produced by a radioactive source was computed by integrating the point dose rate kernel of the corresponding radionuclide over the radioactive line. The point dose rate kernel was computed with Monte Carlo simulation of radiation transport. The edge effects were characterized with three newly defined quantities: longitudinal dose uniformity (LDU), effective coverage length (ECL), and margin length (ML). LDU was defined as the ratio of dose at a distance along the long axis of the vessel to the dose at center. ECL was defined as the length over which the LDU was greater than 0.95. ML was defined as half of the length difference between source length L and ECL, which is essentially the length segment at each edge that is covered by the source physical length but is being underdosed. RESULTS: All beta emitters provided more uniform dose distributions and covered a larger portion of blood vessels longitudinally than photon emitters. Typical MLs were 2-3 mm for beta emitters and 4-6 mm for gamma emitters. As the radial depth of the point of interest increased, both the LDU and ECL decreased and ML increased. The ML increased from 2 to 3 mm for beta emitters and from 4 to 6 mm for photon emitters when the radial depth of the point of interest increased from 1.5 to 2.5 mm (typical proximal and distal media points for a 3-mm diameter lumen). The ML increased with increasing source length for all radionuclides. For beta emitters the ML increased initially from 1.5 mm to more than 2.5 mm as source length increased from 5 to 10 mm. When the source length was longer than 15 mm, the ML remains nearly constant, about 3 mm. For photon emitters, ML increased continuously from 1.5 mm to more than 6.0 mm, as source length increased from 5 to 50 mm. CONCLUSIONS: A formalism to quantify the dose uniformity along the length of a blood vessel undergoing catheter-based intravascular brachytherapy has been developed. This formalism was used to study the edge effects at the ends of several beta and photon sources. The results indicated that for a centered source the ML at each end due to penumbra effects was about 2 to 3 mm for beta emitters; about 4-6 mm for photon emitters. The ML increases as the radial depth of point of interest in the vessel increases. The ML increases also with increasing source length, especially for photon sources.

Brachytherapy↗

Humans use continuous visual feedback from the hand to control both the direction and distance of pointing movements.

Vision of the hand during reaching provides dynamic feedback that can be used to control movement. We investigated the relative contributions of feedback about the direction and distance of the hand relative to a target. Subjects made pointing movements in a 3-D virtual environment, in which a small sphere provided dynamic visual feedback about the position of their unseen fingertip. On a subset of trials, the position of the virtual fingertip was smoothly shifted by 2 cm during movement, either (1) in the direction of movement, which would require adjustments to the distance moved, or (2) orthogonal to the direction of movement, which would require adjustments to the direction moved. Despite not noticing the perturbations, subjects adjusted their movements to compensate for both types of visual shifts. Corrective responses to direction perturbations were observed within 117 ms, and response latencies were invariant to movement speed and perturbation onset time. Initial corrections to distance perturbations were smaller and appeared after longer delays of 130-200 ms, and both the speed and magnitude of responses were reduced for early onset perturbations. Simulations of a feedback control model that optimally integrates visual information over time show that the results can be explained by differences in the sensory noise levels in the visual dimensions relevant for direction and distance control.

Adaptation, Physiological↗

Constructing diffeomorphic representations for the groupwise analysis of nonrigid registrations of medical images.

Groupwise nonrigid registrations of medical images define dense correspondences across a set of images, defined by a continuous deformation field that relates each target image in the group to some reference image. These registrations can be automatic, or based on the interpolation of a set of user-defined landmarks, but in both cases, quantifying the normal and abnormal structural variation across the group of imaged structures implies analysis of the set of deformation fields. We contend that the choice of representation of the deformation fields is an integral part of this analysis. This paper presents methods for constructing a general class of multi-dimensional diffeomorphic representations of deformations. We demonstrate, for the particular case of the polyharmonic clamped-plate splines, that these representations are suitable for the description of deformations of medical images in both two and three dimensions, using a set of two-dimensional annotated MRI brain slices and a set of three-dimensional segmented hippocampi with optimized correspondences. The class of diffeomorphic representations also defines a non-Euclidean metric on the space of patterns, and, for the case of compactly supported deformations, on the corresponding diffeomorphism group. In an experimental study, we show that this non-Euclidean metric is superior to the usual ad hoc Euclidean metrics in that it enables more accurate classification of legal and illegal variations.

Algorithms↗

Structure and phase transitions of alkyl chains on mica.

We use molecular dynamics as a tool to understand the structure and phase transitions [Osman, M. A.; et al. J. Phys. Chem. B 2000, 104, 4433-4439. Osman, M. A.; et al. J. Phys. Chem. B 2002, 106, 653-662] in alkylammonium micas. The consistent force field 91 is extended for accurate simulation of mica and related minerals. We investigate mica sheets with 12 octadecyltrimethylammonium (C(18)) ions or 12 dioctadecyldimethylammonium (2C(18)) ions, respectively, as single and layered structures at different temperatures with periodicity in the xy plane by NVT dynamics. The alkylammonium ions reside preferably above the cavities in the mica surface with an aluminum-rich boundary. The nitrogen atoms are 380-390 pm away from the superficial silicon-aluminum plane. With increasing temperature, rearrangements of C(18) ions on the mica surface are found, while 2C(18) ions remain tethered due to geometric restraints. We present basal-plane spacings in the duplicate structures, tilt angles of the alkyl chains, and gauche-trans ratios to analyze the chain conformation. Agreement with experimental data, where available, is quantitative. In C(18)-mica with less than 100% alkali-ion exchange, the disordered C(18) rods in the island structures [Hayes, W. A.; Schwartz, D. K. Langmuir 1998, 14, 5913-5917] break at 40 degrees C. At 60 degrees C, the headgroups of the C(18) alkyl chains rearrange on the mica surface, and the broken chain backbones assume a coillike structure. The C(18)-mica obtained on fast cooling of this phase is metastable due to slow reverse rearrangements of the headgroups. In 2C(18)-mica with 70-80% ion exchange, the alkali ions are interspersed between the alkyl chains, corresponding to a single phase on the surface. The observed phase transition at approximately 53 degrees C involves an increase of chain disorder (partial melting) of the 2C(18) ions without significant rearrangements on the mica surface. We propose a geometric parameter lambda for the saturation of the surface with alkyl chains, which determines the preferred self-assembly pattern, that is, islands, intermediate, or continuous. lambda allows the calculation of tilt angles in continuous layers on mica or other surfaces. The thermal decomposition seems to be a Hofmann elimination with mica as a base-template.

Journal Article↗

Responses of Purkinje cells in the cerebellar anterior vermis to off-vertical axis rotation.

Responses of 67 Purkinje cells (P-cells) and 44 unidentified neurons (U-cells) located in the cerebellar anterior vermis were recorded in decerebrate cats during off-vertical axis rotation (OVAR). This stimulus consisted of a slow constant velocity (9.4%/s) rotation in the clockwise (CW) and counterclockwise (CCW) directions around an axis inclined by 5 degrees with respect to the vertical. OVAR imposes on the animal head a 5 degrees tilt, whose direction changes continuously over the horizontal plane, thus eliciting a selective stimulation of macular receptors. A total of 27/67 P-cells (40%) and 24/44 U-cells (55%) responded to both CW and CCW rotations. For these bidirectional units, the direction of maximum sensitivity to tilt (Smax) could be identified. Smax directions were distributed over the whole horizontal plane of stimulation. Among bidirectional neurons, 48% of the P-cells and 33% of the U-cells displayed an equal amplitude of modulation during CW and CCW rotations, indicating a cosine-tuned behaviour. In these instances, the temporal phase of the unit response to a given direction of tilt remained constant, while the sensitivity was maximal along the Smax direction and declined with the cosine of the angle between Smax and the tilt direction. The remaining bidirectional units displayed unequal amplitudes of modulation during CW and CCW rotations. For these neurons, a nonzero sensitivity along the null direction was expected and the response phase varied as a function of stimulus direction. Finally, 31% and 23% of P-cells and U-cells, respectively, responded during OVAR in one direction only (unidirectional units). This behaviour predicts equal sensitivities along any tilt direction in the horizontal plane and a response phase that changes linearly with the stimulus direction. The posibility that the tested neurons formed a population which coded the direction of head tilt in space was also investigated. The data from the whole population of cells were analysed using a modified version of vectorial analysis. This model assumes that for a particular tilt each cell makes vectorial contributions; the vectorial sum of these contributions represent the outcome of the population code and points in the direction of head tilt in space. Thus, a dynamic head tilt along four representative directions was simulated. For each of the four directions, 12 population vectors were calculated at regular time intervals so as to cover an entire cycle of head tilt. The results indicate that for each selected time in the cycle the direction of the population vector closely corresponded to that of the head tilt, while its amplitude was related to the amount of head tilt. These data were particularly obtained for the P-cells. In view of their efferent connections, the cerebellar anterior vermis may provide a framework for the spatial organization of vestibulospinal reflexes induced by stimulation of otolith receptors.

Animals↗

Cooperative regulation of myosin-actin interactions by a continuous flexible chain II: actin-tropomyosin-troponin and regulation by calcium.

The model of myosin regulation by a continuous tropomyosin chain is generalized to a chain of tropomyosin-troponin units. Myosin binding to regulated actin is cooperative and initially inhibited by the chain as before. In the absence of calcium, myosin is further inhibited by the binding of troponin-I to actin, which through the whole of troponin pins the tropomyosin chain in a blocking position; myosin and TnI compete for actin and induce oppositely-directed chain kinks. The model predicts equilibrium binding curves for myosin-S1 and TnI as a function of their first-order affinities K(S1) and L(TI). Myosin is detached by the actin binding of TnI, but TnI is more efficiently detached by myosin when the kink size (typically nine to ten actin sites) spans the seven-site spacing between adjacent TnI molecules. An allosteric mechanism is used for coupling the detachment of TnI to calcium binding by TnC. With thermally activated TnI kinks (kink energy B approximately k(B)T), TnI also binds cooperatively to actin, producing cooperative detachment of myosin and biphasic myosin-calcium Hill plots, with Hill coefficients of 2 at high calcium and 4-6 at low calcium as observed in striated muscle. The theory also predicts the cooperative effects observed in the calcium loading of TnC.

Actins↗

Modeling genome evolution with a diffusion approximation of a birth-and-death process.

MOTIVATION: In our previous studies, we developed discrete-space birth, death and innovation models (BDIMs) of genome evolution. These models explain the origin of the characteristic Pareto distribution of paralogous gene family sizes in genomes, and model parameters that provide for the evolution of these distributions within a realistic time frame have been identified. However, extracting the temporal dynamics of genome evolution from discrete-space BDIM was not technically feasible. We were interested in obtaining dynamic portraits of the genome evolution process by developing a diffusion approximation of BDIM. RESULTS: The diffusion version of BDIM belongs to a class of continuous-state models whose dynamics is described by the Fokker-Plank equation and the stationary solution could be any specified Pareto function. The diffusion models have time-dependent solutions of a special kind, namely, generalized self-similar solutions, which describe the transition from one stationary distribution of the system to another; this provides for the possibility of examining the temporal dynamics of genome evolution. Analysis of the generalized self-similar solutions of the diffusion BDIM reveals a biphasic curve of genome growth in which the initial, relatively short, self-accelerating phase is followed by a prolonged phase of slow deceleration. This evolutionary dynamics was observed both when genome growth started from zero and proceeded via innovation (a potential model of primordial evolution), and when evolution proceeded from one stationary state to another. In biological terms, this regime of evolution can be tentatively interpreted as a punctuated-equilibrium-like phenomenon whereby evolutionary transitions are accompanied by rapid gene amplification and innovation, followed by slow relaxation to a new stationary state.

Algorithms↗

Kinetics of amyloplast movement in cress root statocytes under different gravitational loads.

In order to investigate the movement of a statolith complex along the longitudinal axis of root cap statocytes under different mass accelerations, a series of experiments with Lepidium sativum L. in an automatically operating centrifuge during the Bion-11 satellite flight and on a centrifuge-clinostat have been performed. During spaceflight, roots were grown for 24 h under root-tip-directed centrifugal 1-g acceleration, then exposed to microgravity for 6, 12 and 24 min and chemically fixed. During the first 6 min of microgravity, the statoliths moved towards the cell center with a mean velocity of 0.31 +/- 0.04 micrometers/min, which decreased to 0.12 +/- 0.01 micrometers/min within subsequent 12-24 min period. The mean relative position of the statolith complex in respect to the distal cell wall (% of total cell length) increased from 24.0 +/- 0.5% in 1 g-grown roots to 38.8 +/- 0.8% in roots exposed for 24 min to microgravity, but remained smaller than in roots grown continuously in microgravity (48.0 +/- 0.7%). The properties of the statolith movement away from the distal pole of the statocyte were studied in roots grown for 24 h vertically under 1 g and then placed for 6 min on a fast rotating clinostat (50 rpm) or 180 degrees inverted. After 2 min of both treatments, the mean relative position of the statoliths increased by about 10% versus its initial position. Later on, the proximal displacement of amyloplasts slowed down under simulated weightlessness, while it proceeded at a constant velocity under 1 g inversion. In roots grown on the clinostat and then exposed to 1 g in the longitudinal direction, amyloplast sedimentation away from the central region of statocyte was similar at the beginning of distal and proximal 6-min 1-g stimulation. However, at the end of this period statolith displacement was more pronounced in proximal direction as compared to distal. It is proposed that statolith position in the statocyte of a vertical root is controlled by the force of gravity, however, the intracellular forces, first of all those generated by the network of the cytoskeleton, are manifested when an usual orientation of the organ is changed or the statocytes are exposed to microgravity and clinorotation.

Centrifugation↗

Patterns of and mechanisms for shock-induced polarization in the heart: a bidomain analysis.

This paper examines the combined action of cardiac fiber curvature and transmural fiber rotation in polarizing the myocardium under the conditions of a strong electrical shock. The study utilizes a three-dimensional finite element model and the continuous bidomain representation of cardiac tissue to model steady-state polarization resulting from a defibrillation-strength uniform applied field. Fiber architecture is incorporated in the model via the shape of the heart, an ellipsoid of variable ellipticity index, and via an analytical function, linear or nonlinear, describing the transmural fiber rotation. Analytical estimates and numerical results are provided for the location and shape of the "bulk" polarization (polarization away from the tissue boundaries) as a function of the fiber field, or more specifically, of the conductivity changes in axial and radial direction with respect to the applied electrical field lines. Polarization in the tissue "bulk" is shown to exist only under the condition of unequal anisotropy ratios in the extra- and intracellular spaces. Variations in heart geometry and, thus, fiber curvature, are found to lead to change in location of the zones of significant membrane polarization. The transmural fiber rotation function modulates the transmembrane potential profile in the radial direction. A higher gradient of the transmural transmembrane potential is observed in the presence of fiber rotation as compared to the no rotation case. The analysis presented here is a step forward in understanding the interaction between tissue structure and applied electric field in establishing the pattern of membrane polarization during the initial phase of the defibrillation shock.

Anisotropy↗

Chronic cerebral vasospasm: effect of calcium antagonists.

The efficacy of the calcium antagonists nifedipine and nimodipine was evaluated in a multiinjection canine model of severe chronic cerebral vasospasm. Each of 21 adult mongrel dogs (15 to 20 kg) was assigned to one of four experimental groups. All animals received a total of 15 ml of fresh, unheparinized arterial blood via three cisterna magna injections. Selective left vertebral arteriography was performed 1 week before and exactly 7 days after the simulated subarachnoid hemorrhage. Treatment with calcium antagonists was initiated at 24 hours and continued for 7 consecutive days. Comparisons were based on the percentage of reduction in basilar artery diameter. On a milligram/kilogram basis, we used the manufacturer's maximal recommended daily dosages of nifedipine, whereas the dosages of nimodipine used were 3 to 7 times greater than that reported to be therapeutically effective in reducing the incidence of severe deficits from vasospasm in patients with aneurysmal subarachnoid hemorrhage. In this laboratory trial, systemic treatment with calcium antagonists did not prevent or significantly reduce chronic arterial narrowing. In the control group, spasm reduced basilar artery diameter an average of 71% +/- 11 (SD). In the group treated with nifedipine, 10 mg orally every 6 hours, vessel diameter was reduced an average of 58% +/- 13%. In those animals treated with nimodipine, 20 or 40 mg orally every 4 hours, the basilar artery diameter was decreased an average of 59% +/- 8 and 56% +/- 7, respectively. A preliminary trial using direct intracisternal administration of these agents demonstrated increased vessel diameter within 20 minutes in four of six animals, supporting other reports that this route of administration may prove more efficacious in the treatment of chronic cerebral vasospasm.

Animals↗

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↗

Experimental studies of transient mass transfer and reaction in the liver: interpretation with a heterogeneous compartment model.

The uptake and metabolism of lipophilic compounds by the liver were studied by administering a model compound, lidocaine, to the isolated rat liver. Lidocaine was continuously infused into the liver until steady state was reached. Subsequent step changes in the inlet concentration were used to obtain information on rates of cellular uptake and release and to assess the extent of mixing within the organ. A simple heterogeneous model combining mass transfer and enzyme reactions was required to simulate the effluent levels of lidocaine and two primary metabolites, monoethylglycinexylidide and 3-hydroxylidocaine. The rate constants for uptake and release of lidocaine were 1200 and 46 min-1, respectively. The rate-limiting step was intracellular reaction, with a rate constant of 0.49 min-1. Although the rate of lidocaine uptake was fast, it was 50 times slower than the rate of facilitated uptake of galactose, a fact suggesting passive transport of lidocaine between the tissue and the vasculature. The rates of mass transfer of lidocaine and its metabolites differed, but the ratios of the rate of uptake to the rate of release were the same. The results suggested that all three species had an affinity for the cellular region of the liver; concentrations in tissue were approximately five times greater than concentrations in effluent. Because of the large capacity of the organ for uptake of lidocaine and its metabolites, concentrations from washout experiments were controlled by linear mass transfer from the tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗