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[Reconstruction methods for 3D imaging and quantification of intracoronary ultrasound cross-sectional images using biplanar fluoroscopy. Initial experiences in vitro and in vivo].

In this investigation, we studied the feasibility of 3D-reconstruction from 2D cross-sectional intracoronary ultrasound images. A computer-aided, automated 3D-reconstruction was used to generate cylindrical and sagittal format of vessels in vitro (n = 9) and in vivo (n = 48). Ultrasound 2D-images were acquired with a 20 MHz mechanical intracoronary ultrasound catheter (Boston Scientific). A slow pullback (about 1 mm/s) of the catheter was performed during continuous recording of the ultrasound images. The recorded 2D-images were then fed to an image processing computer. Correction and scaling of the axial vessel dimensions was performed by the assessment of the catheter position in the simultaneously recorded biplane fluoroscopy. Digitized data were then processed to 3D-images with use of voxel space modeling. The 3D-views from any plane can be reconstructed. The in-vitro study demonstrated that the reconstructed images were able to correctly portray the pathological changes of the vessel wall in all specimen as proved by pathologic examination. In the in-vivo study, 3D-reconstruction provided not only a spatial visualization of the coronary arterial disorders (such as coronary aneurysm, coronary dissection, spontaneous plaque rupture etc.) but also provides the potential to quantify the mass of lesions. By combining sagittal and cylindrical views, 3D-reconstruction enables longitudinal and orthogonal imaging of the both the vessel lumen and vessel wall, therefore, it has the advantage of cross-sectional viewing as obtained from intracoronary ultrasound and the longitudinal viewing as derived from coronary angiography. These preliminary results of the study indicate that 3D-reconstruction of coronary segments is a promising technique for studying coronary artery disease. Analysis can be based not only on single or multiple cross-sectional images but also on vessel segments facilitating serial studies as for instance studies assessing the progression and regression of atherosclerosis.

Aortic Dissection↗

Individual-based modelling of biofilms.

Understanding the emergence of the complex organization of biofilms from the interactions of its parts, individual cells and their environment, is the aim of the individual-based modelling (IbM) approach. This IbM is version 2 of BacSim, a model of Escherichia coli colony growth, which was developed into a two-dimensional multi-substrate, multi-species model of nitrifying biofilms. It was compared with the established biomass-based model (BbM) of Picioreanu and others. Both models assume that biofilm growth is due to the processes of diffusion, reaction and growth (including biomass growth, division and spreading). In the IbM, each bacterium was a spherical cell in continuous space and had variable growth parameters. Spreading of biomass occurred by shoving of cells to minimize overlap between cells. In the BbM, biomass was distributed in a discrete grid and each species had uniform growth parameters. Spreading of biomass occurred by cellular automata rules. In the IbM, the effect of random variation of growth parameters of individual bacteria was negligible in contrast to the E. coli colony model, because the heterogeneity of substrate concentrations in the biofilm was more important. The growth of a single cell into a clone, and therefore also the growth of the less abundant species, depended on the randomly chosen site of attachment, owing to the heterogeneity of substrate concentrations in the biofilm. The IbM agreed with the BbM regarding the overall growth of the biofilm, due to the same diffusion-reaction processes. However, the biofilm shape was different due to the different biomass spreading mechanisms. The IbM biofilm was more confluent and rounded due to the steady, deterministic and directionally unconstrained spreading of the bacteria. Since the biofilm shape is influenced by the spreading mechanism, it is partially independent of growth, which is driven by diffusion-reaction. Chance in initial attachment events modifies the biofilm shape and the growth of single cells because of the high heterogeneity of substrate concentrations in the biofilm, which again results from the interaction of diffusion-reaction with spreading. This stresses the primary importance of spreading and chance in addition to diffusion-reaction in the emergence of the complexity of the biofilm community.

Algorithms↗

Multipolar representation of protein structure.

BACKGROUND: That the structure determines the function of proteins is a central paradigm in biology. However, protein functions are more directly related to cooperative effects at the residue and multi-residue scales. As such, current representations based on atomic coordinates can be considered inadequate. Bridging the gap between atomic-level structure and overall protein-level functionality requires parameterizations of the protein structure (and other physicochemical properties) in a quasi-continuous range, from a simple collection of unrelated amino acids coordinates to the highly synergistic organization of the whole protein entity, from a microscopic view in which each atom is completely resolved to a "macroscopic" description such as the one encoded in the three-dimensional protein shape. RESULTS: Here we propose such a parameterization and study its relationship to the standard Euclidian description based on amino acid representative coordinates. The representation uses multipoles associated with residue Calpha coordinates as shape descriptors. We demonstrate that the multipoles can be used for the quantitative description of the protein shape and for the comparison of protein structures at various levels of detail. Specifically, we construct a (dis)similarity measure in multipolar configuration space, and show how such a function can be used for the comparison of a pair of proteins. We then test the parameterization on a benchmark set of the protein kinase-like superfamily. We prove that, when the biologically relevant portions of the proteins are retained, it can robustly discriminate between the various families in the set in a way not possible through sequence or conventional structural representations alone. We then compare our representation with the Cartesian coordinate description and show that, as expected, the correlation with that representation increases as the level of detail, measured by the highest rank of multipoles used in the representation, approaches the dimensionality of the fold space. CONCLUSION: The results described here demonstrate how a granular description of the protein structure can be achieved using multipolar coefficients. The description has the additional advantage of being immediately generalizable for any residue-specific property therefore providing a unitary framework for the study and comparison of the spatial profile of various protein properties.

Algorithms↗

Rigorous Green's function formulation for transmembrane potential induced along a 3-D infinite cylindrical cell.

The quasi-static electromagnetic field interaction with three-dimensional infinite-cylindrical cell is investigated for both intracellular (IPS) and extracellular (EPS) current point-source excitation. The induced transmembrane potential (TMP), expressed conventionally via Green's function, may alternatively be expanded into a faster-converging representation using a complex contour integration, consisting of an infinite-discrete set of exponentially decaying oscillating modes (corresponding to complex eigenvalues) and a continuous source-mode convolution integral. The dominant contributions for both the IPS and EPS problems are obtained in simple closed-form expressions, including well documented special mathematical functions. In the IPS case, the dominant modal contribution (of order zero)--an exact solution of the well-known cable equation--is explicitly and analytically corrected by the imaginary part of its eigenvalue and the source-mode convolution contribution. However, the TMP along a fiber was shown to decay at infinity algebraically and not exponentially, as predicted by the classic cable equation solution. In the EPS case, the dominant contribution is expressed as a source-mode convolution integral. However, for a long EPS distance (e.g., >10 cable length constant) the order-one-modes involved in the convolution is not a solution of the cable equation. Only for shorter EPS distance should the cable equation solution (i.e., the order zero dominant mode) be included in addition to the modes of order one. For on-membrane EPS location, additional modes should be included as well. In view of our EPS result, we suggest that the cable equation modeling existing in the literature and related to functional electrical stimulation for EPS problems, should be critically reviewed and corrected.

Axons↗

Breast cancer screening; cost-effective in practice?

The main aim of national breast screening is a reduction in breast cancer mortality. The data on the reduction in breast cancer mortality from three (of the five) Swedish trials in particular gave rise to the expectation that the Dutch programme of 2-yearly screening for women aged 50-70 would produce a 16% reduction in the total population. In all likelihood, many of the years of life gained as a result of screening are enjoyed in good health. According to its critics the actual benefit that can be achieved from the national breast cancer screening programmes is overstated. Considerable benefits have recently been demonstrated in England and Wales. However, the fall was so considerable in such a relatively short space of time that screening (started in 1987) was thought to only have played a small part. As far as the Dutch screening programme is concerned it is still too early to reach any conclusions about a possible reduction in mortality. The first short-term results of the screening are favourable and as good as (or better than) expectations. In Swedish regions where mammographic screening was introduced, a 19% reduction in breast cancer mortality can be estimated at population level, and recently a 20% reduction was presented in the UK. In countries where women are expected to make appointments for screening themselves, the attendance figures are significantly lower and the quality of the process as a whole is sometimes poorer. The benefits of breast cancer screening need to be carefully balanced against the burden to women and to the health care system. Mass breast screening requires many resources and will be a costly service. Cost-effectiveness of a breast cancer screening programme can be estimated using a computer model. Published cost-effectiveness ratios may differ tremendously, but are often the result of different types of calculation, time periods considered, including or excluding downstream cost. The approach of simulation and estimation is here the same for all countries. The effects of a breast-screening program depend on many factors, such as the epidemiology of the disease, the health care system, costs of health care, the quality of the screening programme and the attendance rate. The estimated CE-ratio ranges from 2650 euros per life-year gained in Navarra to 9650 in Germany. Although relatively low incidence levels expected, the CE-ratio in Navarra is most favourable probably due to a relatively unfavourable clinical stage distribution before screening and the increasing incidence. The UK has a screening situation that is almost similar with the Netherlands. Therefore, the CE-ratios of both countries are comparable. The differences between countries make it impossible to set up one uniform screening policy. The theoretical outcomes of the benefit that can be achieved are generally from small-scale trials involving a limited number of experts, persons examined, and areas. On a national scale, with hundreds of professional practitioners, it can be expected to be more difficult to attain uniform quality. Continuous quality control, monitoring and evaluation are therefore crucial.

Aged↗

Effect of standing or walking on physiological changes induced by head down bed rest: implications for spaceflight.

BACKGROUND/HYPOTHESIS: To simulate exposure to microgravity and to determine the effectiveness of intermittent exposure to passive and active +1 Gz force (head-to-foot) in preventing head-down bed rest (HDBR) deconditioning, 4 d of 6 degrees HDBR were used. METHODS: Volunteers were 9 males, 30-50 yr, who performed periodic standing or controlled walking for 2 or 4 h.d-1 in 15-min bouts, one bout per hour, or remained in a continuous HDBR control condition (0 Gz). RESULTS: Standing 4 h (S4) completely prevented, and standing 2 h (S2) partially prevented, decreases in post-HDBR orthostatic tolerance (survival rates with 30 min of upright tilt at 60 degrees). Walking, both 2 h (W2) and 4 h (W4), and S4 attenuated decreases in peak oxygen uptake compared to 0 Gz. Compared to 0 Gz, both S4 and W4 attenuated plasma volume loss during HDBR. Urinary Ca2+ excretion increased over time with HDBR; the quadratic trend for urinary Ca2+, however, was attenuated with W2 and W4. CONCLUSIONS: We concluded that various physiological systems benefit differentially from passive +1 Gz or activity in +1 Gz and, in addition to the duration of the stimulus, the number of exposures to postural stimuli may be an important moderating factor.

Adult↗

A quantitative evaluation of the AVITEWRITE model of handwriting learning.

Much sensory-motor behavior develops through imitation, as during the learning of handwriting by children. Such complex sequential acts are broken down into distinct motor control synergies, or muscle groups, whose activities overlap in time to generate continuous, curved movements that obey an inverse relation between curvature and speed. The adaptive vector integration to endpoint handwriting (AVITEWRITE) model of Grossberg and Paine (2000) [A neural model of corticocerebellar interactions during attentive imitation and predictive learning of sequential handwriting movements. Neural Networks, 13, 999-1046] addressed how such complex movements may be learned through attentive imitation. The model suggested how parietal and motor cortical mechanisms, such as difference vector encoding, interact with adaptively-timed, predictive cerebellar learning during movement imitation and predictive performance. Key psychophysical and neural data about learning to make curved movements were simulated, including a decrease in writing time as learning progresses; generation of unimodal, bell-shaped velocity profiles for each movement synergy; size scaling with isochrony, and speed scaling with preservation of the letter shape and the shapes of the velocity profiles; an inverse relation between curvature and tangential velocity; and a two-thirds power law relation between angular velocity and curvature. However, the model learned from letter trajectories of only one subject, and only qualitative kinematic comparisons were made with previously published human data. The present work describes a quantitative test of AVITEWRITE through direct comparison of a corpus of human handwriting data with the model's performance when it learns by tracing the human trajectories. The results show that model performance was variable across the subjects, with an average correlation between the model and human data of 0.89+/-0.10. The present data from simulations using the AVITEWRITE model highlight some of its strengths while focusing attention on areas, such as novel shape learning in children, where all models of handwriting and the learning of other complex sensory-motor skills would benefit from further research.

Attention↗

Increased orthostatic blood pressure variability after prolonged head-down tilt.

The effect of simulated weightlessness on orthostatic blood pressure regulation was evaluated with passive 70 degrees head-up tilt (HUT) after 10 days 6 degrees head-down tilt (HDT). Six healthy male volunteers were studied. Continuous recording of finger blood pressure (BP) was obtained non-invasively with a FinapresTM device. Instantaneous heart rate (HR) was derived from the electrocardiogram. To quantify orthostatic BP variability, a fast fourier transform (FFT) of the beat-by-beat BP- and RR-interval values was performed. Control HR before HUT after the 10-day HDT period was increased, probably due to an arousal state of the test subjects. The change in BP induced by HUT was not influenced by 10 days' HDT, in contrast to the HR rise which increased from 24 +/- 2 beats/min to 41 +/- 7 beats/min (P less than 0.05). After HDT the total variance in orthostatic BP almost doubled. FFT indicated that this increase in variance can be ascribed to BP oscillations with a frequency of around 0.1 Hz. In three subjects transient HR decelerations during HUT after HDT were observed. Analysis of the relationship between BP and HR in the transients showed that each HR decrease was preceded by a BP increase above normal. These HR decelerations seemed, therefore, to be an effect of the vagal part of the arterial baroreflex and did not necessary signal an impending vasovagal syncope. The present study indicates that although 10 days' HDT do not influence absolute BP responses to 70 degrees HUT BP was maintained by an increased sympathetic activity, reflected by an increased HR response and an augmented variance in BP around 0.1 Hz.

Adult↗

Weightlessness experiments on Biosatellite II.

Four experiments in the aft compartment of Biosatellite II investigated the broad question of the effect of nearly zero gravity on the development, morphology and metabolism of plants and animals. The fertilization and development of the egg of a vertebrate (the frog, Rana pipiens), the feeding and growth of a protozoan (the giant amoeba, Pelomyxa carolinensis), the orientation of leaves and petioles of a young dicotyledon (pepper plants, Capsicum annuum) and the morphogenesis, orientation, histochemistry and biochemistry of a monocotyledon seedling (wheat, Triticum vulgare) gave a broad scope. All are known to have specific responses to normal gravity and changes in them might be expected to reflect the effects of orbital flight on living organisms. No differences in development of the frog eggs could be detected. Unfortunately, the 3 1/2 hour delay in launch allowed the first cleavage (the stage most sensitive to inversion) to appear before launch. Although the orbited embryos were somewhat slower to reach certain stages of development, recovered embryos developed just as did the controls. The amoebae fed normally while in orbit, and specimens fixed in orbit retained the ordinary heteropodal shape. Growth rates of orbited amoebae, both fed and starved, were slower than controls following reentry and recovery procedures. In continuous-fed organisms there was little or no effect of flight detectable in growth rate or actual number of divisions. Electron micrographs showed no abnormalities and few differences between flight and control organisms. The pepper plants were photographed in orbit at ten-minute intervals, as were the clinostat and erect controls. The subsequent measurement of photographs showed that in the orbited plants all leaves showed epinasty, the interaxial angle decreasing by 20-60 degrees C. Plants on the horizontal clinostat behaved comparably, but recovered more rapidly than orbited plants when returned to the normal erect position. Although the maximum age of wheat seedlings was only 65 hours, coleoptile and root growth rates during that time had not been significantly altered by flight or by slow rotation on a horizontal clinostat. There was some evidence that growth was accelerated after normal gravity was restored. The orientation of coleoptiles and of primary and lateral roots of orbited plants varied significantly from the normal erect seedlings but was almost identical with that of clinostat plants. The Periodic-Acid-Schiff technique on sectioned material showed starch grains at the bottom of cells of erect control coleoptile and root tips, while in orbited and clinostated plants the grains were located more or less at random. Histochemical differences between clinostat and orbited tissues are apparent however. Peroxidase localization varied and its activity was higher in both clinostat and orbited tissues; five other enzymes studied biochemically showed no differences. These experiments all suggest that there is no deleterious effect on living organisms or their activities from short-term weightlessness. Several results indicate that the horizontal clinostat may simulate the weightless state effectively here on Earth.

Amoeba↗

Periodic structures and diurnal variation in blood pressure and heart rate in relation to microgravity on space station MIR.

Four Russian crew members were studied on space station MIR, and blood pressure (BP) and heart rate (HR) data were continuously collected. BP and HR data were collected on earth 1 day before orbital flight to the space station, then at weeks 8, 16 and 24 during space flight, and again 1 or 2 days after returning to earth. Time serial data for BP and HR were analyzed by spectral analysis with the MemCalc system (Suwa Trust, Sapporo, Japan). Periodic structures of diurnal variation in systolic blood pressure (SBP), diastolic blood pressure (DBP) and HR were compared at 24-hour, 12-hour and 8-hour intervals, these being determined as the main periodic components for the assessment of BP and HR variability. The 24-h mean levels of SBP and HR during space flight were unchanged. Waking SBP was not different from pre-flight values. During sleep, in-flight changes in HR did not differ from pre-flight values. SBP during sleep in orbit increased to over pre-flight values. Waking DBP was reduced during flight. The SBP and HR phases over a 24-hour cycle were shortened with a more pronounced shortening in weeks 8 and 16 compared with pre-flight values, and at week 24 recovered to preflight values. The 12, 8-hour-cycle remained unchanged, and were similar to pre-flight values. At the space station, the astronauts' mission was carried out under strict control of sleeping and waking hours; therefore, their 24-hour schedule is an artificially constructed situation. Main periodicity structures were maintained by strict control of lifestyle during long-term space flight. The conclusions reached were as follows: 1) SBP levels during sleep in a space environment increased compared with those on earth; 2) the periodicity phase of BP and HR shifted toward to 24-hour cycle as a result of long-term space flight, even though these periods shortened after a few months compared with pre-space flight values.

Adult↗

Hypoxia-induced increases in pulmonary transvascular protein escape in rats. Modulation by glucocorticoids.

Pulmonary edema after ascent to altitude is well recognized but its pathogenesis is poorly understood. To determine whether altitude exposure increases lung vascular permeability, we exposed rats to a simulated altitude of approximately 14,500 feet (barometric pressure [Pb] 450 Torr) and measured the pulmonary transvascular escape of radiolabeled 125I-albumin corrected for lung blood content with 51Cr-tagged red blood cells (protein leak index = PLI). Exposures of 24 and 48 h caused significant increases in PLI (2.30 +/- 0.08 and 2.40 +/- 0.06) compared with normoxic controls (1.76 +/- 0.06), but brief hypoxic exposures of 1-13 h produced no increase in PLI, despite comparable increases in pulmonary artery pressure. There were associated increases in gravimetric estimates of lung water in the altitude-exposed groups and perivascular edema cuffs on histologic examination. Normobaric hypoxia (48 h; fractional inspired oxygen concentration [FIO2] = 15%) also increased lung transvascular protein escape and lung water. Dexamethasone has been used to prevent and treat altitude-induced illnesses, but its mechanism of action is unclear. Dexamethasone (0.5 or 0.05 mg/kg per 12 h) started 12 h before and continued during 48 h of altitude exposure prevented the hypoxia-induced increases in transvascular protein escape and lung water. Hemodynamic measurements (mean pulmonary artery pressure and cardiac output) were unaffected by dexamethasone, suggesting that its effect was not due to a reduction in pulmonary artery pressure or flow. The role of endogenous glucocorticoid activity was assessed in adrenalectomized rats that showed augmented hypoxia-induced increases in transvascular protein escape, which were prevented by exogenous glucocorticoid replacement. In summary, subacute hypoxic exposures increased pulmonary transvascular protein escape and lung water in rats. Dexamethasone prevented these changes independent of reductions of mean pulmonary artery pressure or flow, whereas adrenalectomy increased pulmonary vascular permeability and edema at altitude. Increases in vascular permeability in hypoxia could contribute to the development of high-altitude pulmonary edema and endogenous glucocorticoids may have an important influence on pulmonary vascular permeability in hypoxia.

Adrenalectomy↗

Gamma knife radiosurgery as a primary treatment for prolactinomas.

OBJECT: The purpose of this study was to estimate the efficacy of gamma knife radiosurgery (GKS) in controlling tumor growth and endocrinopathy associated with prolactinomas. METHODS: Between 1993 and 1997, 164 of 469 patients with pituitary adenomas treated by GKS harbored prolactinomas. The dose to the tumor margin ranged from 9 to 35 Gy (mean 31.2 Gy), and the visual pathways were exposed to a dose of less than 10 Gy. The mean tumor diameter was 13.4 mm. The mean follow-up time for 128 cases was 33.2 months (range 6-72 months). Tumor control was observed in all but two patients who underwent surgery 18 and 36 months, respectively, after GKS. Clinical cure was achieved in 67 cases. Clinical improvement was noted with a decrease in the hyperprolactinemia after GKS. Nonetheless, in 31 (29%) of 108 patients who were followed for more than 2 years no improvement in serum prolactin levels was demonstrated, although this could be normalized by bromocriptine administration after treatment. Nine infertile women became pregnant 2 to 13 months after GKS and all gave birth to normal children. There was no visual deterioration related to GKS. Five women experienced premature menopause. In these patients there was subtotal disappearance of the tumor and an empty sella developed. CONCLUSIONS: Gamma knife radiosurgery as a primary treatment for prolactinomas can be safe and effective both for controlling tumor growth and for normalization of prolactin hypersecretion. A higher margin dose (> or = 30 Gy) seemed to be associated with a better clinical outcome. Gamma knife radiosurgery may make prolactinomas more sensitive to the bromocriptine.

Humans↗

A new parametric method based on S-distributions for computing receiver operating characteristic curves for continuous diagnostic tests.

Receiver operating characteristic (ROC) curves provides a method for evaluating the performance of a diagnostic test. These curves represent the true positive ratio, that is, the true positives among those affected by the disease, as a function of the false positive ratio, that is, the false positives among the healthy, corresponding to each possible value of the diagnostic variable. When the diagnostic variable is continuous, the corresponding ROC curve is also continuous. However, estimation of such curve through the analysis of sample data yields a step-line, unless some assumption is made on the underlying distribution of the considered variable. Since the actual distribution of the diagnostic test is seldom known, it is difficult to select an appropriate distribution for practical use. Data transformation may offer a solution but also may introduce a distortion on the evaluation of the diagnostic test. In this paper we show that the distribution family known as the S-distribution can be used to solve this problem. The S-distribution is defined as a differential equation in which the dependent variable is the cumulative. This special form provides a highly flexible family of distributions that can be used as models for unknown distributions. It has been shown that classical statistical distributions can be represented accurately as S-distributions and that they occur in a definite subspace of the parameter space corresponding to the whole S-distribution family. Consequently, many other distributional forms that do not correspond to known distributions are provided by the S-distribution. This property can be used to model observed data for unknown distributions and is very useful in constructing parametric ROC curves in those cases. After fitting an S-distribution to the observed samples of diseased and healthy populations, ROC curve computation is straightforward. A ROC curve can be considered as the solution of a differential equation in which the dependent variable is the ratio of true positives and the independent variable is the ratio of false positives. This equation can be easily obtained from the S-distributions fitted to observed data. Using these results, we can compute pointwise confidence bands for the ROC curve and the corresponding area under the curve. We shall compare this approach with the empirical and the binormal methods for estimating a ROC curve to show that the S-distribution based method is a useful parametric procedure.

Area Under Curve↗

The timing of control signals underlying fast point-to-point arm movements.

It is known that proprioceptive feedback induces muscle activation when the facilitation of appropriate motoneurons exceeds their threshold. In the suprathreshold range, the muscle-reflex system produces torques depending on the position and velocity of the joint segment(s) that the muscle spans. The static component of the torque-position relationship is referred to as the invariant characteristic (IC). According to the equilibrium-point (EP) hypothesis, control systems produce movements by changing the activation thresholds and thus shifting the IC of the appropriate muscles in joint space. This control process upsets the balance between muscle and external torques at the initial limb configuration and, to regain the balance, the limb is forced to establish a new configuration or, if the movement is prevented, a new level of static torques. Taken together, the joint angles and the muscle torques generated at an equilibrium configuration define a single variable called the EP. Thus by shifting the IC, control systems reset the EP. Muscle activation and movement emerge following the EP resetting because of the natural physical tendency of the system to reach equilibrium. Empirical and simulation studies support the notion that the control IC shifts and the resulting EP shifts underlying fast point-to-point arm movements are gradual rather than step-like. However, controversies exist about the duration of these shifts. Some studies suggest that the IC shifts cease with the movement offset. Other studies propose that the IC shifts end early in comparison to the movement duration (approximately, at peak velocity). The purpose of this study was to evaluate the duration of the IC shifts underlying fast point-to-point arm movements. Subjects made fast (hand peak velocity about 1.3 m/s) planar arm movements toward different targets while grasping a handle. Hand forces applied to the handle and shoulder/elbow torques were, respectively, measured from a force sensor placed on the handle, or computed with equations of motion. In some trials, an electromagnetic brake prevented movements. In such movements, the hand force and joint torques reached a steady state after a time that was much smaller than the movement duration in unobstructed movements and was approximately equal to the time to peak velocity (mean difference < 80 ms). In an additional experiment, subjects were instructed to rapidly initiate corrections of the pushing force in response to movement arrest. They were able to initiate such corrections only when the joint torques and the pushing force had practically reached a steady state. The latency of correction onset was, however, smaller than the duration of unobstructed movements. We concluded that during the time at which the steady state torques were reached, the control pattern of IC shifts remained the same despite the movement block. Thereby the duration of these shifts did not exceed the time of reaching the steady state torques. Our findings are consistent with the hypothesis that, in unobstructed movements, the IC shifts and resulting shifts in the EP end approximately at peak velocity. In other words, during the latter part of the movement, the control signals responsible for the equilibrium shift remained constant, and the movement was driven by the arm inertial, viscous and elastic forces produced by the muscle-reflex system. Fast movements may thus be completed without continuous control guidance. As a consequence, central corrections and sequential commands may be issued rapidly, without waiting for the end of kinematic responses to each command, which may be important for many motor behaviours including typing, piano playing and speech. Our study also illustrates that the timing of the control signals may be substantially different from that of the resulting motor output and that the same control pattern may produce different motor outputs depending on external conditions.

Adult↗

Aging reduces the efficacy of the simulated epidural test dose in anesthetized adults.

UNLABELLED: Aging is associated with reduced beta-adrenergic responsiveness. However, the age-related effects on hemodynamic changes and effectiveness of a simulated epidural IV test dose have not been defined during general anesthesia. We studied 20 (140 total) consecutive patients (ASA physical status I) assigned in each of the following age groups after endotracheal intubation and during stable end-tidal sevoflurane 2% and 67% nitrous oxide anesthesia (in yr): 10s, 20s, 30s, 40s, 50s, 60s, and 70s. Each group first received normal saline 3 mL IV, followed 4 min later by 1.5% lidocaine 3 mL plus 15 microg epinephrine (1:200,000) IV for 5 s. Heart rate (HR) and systolic blood pressure (SBP) were continuously monitored for 4 min after saline administration and the test dose injections. None receiving IV saline and all patients receiving IV test dose in age groups 10s to 50s developed HR increases > or = 10 bpm, whereas 17 and 13 patients met this HR criterion in age groups 60s and 70s (85% and 65% sensitivities), respectively. There was a significant inverse correlation between the maximum HR increase and the age (P: < 0.001 by Spearman's rank correlation). However, none receiving saline and all patients receiving IV test dose in all age groups developed SBP increases of 15 mm Hg, resulting in 100% efficacy based on the SBP criterion. We conclude that during stable sevoflurane anesthesia administration (a) the efficacy based on the HR criterion for detecting accidental intravascular injection of the epidural test dose is age-dependent, (b) the HR criterion may be clinically applicable only in patients <60 yr of age, and (c) the SBP criterion is effective for all age groups studied. IMPLICATIONS: To determine whether an epidurally administered local anesthetic has been unintentionally injected into a blood vessel, a small dose of epinephrine is often added to a local anesthetic. We found that an increase in systolic blood pressure > or = 15 mm Hg is a more useful indicator than an increase in heart rate > or = 10 bpm in the patients > or = 60 yr old during stable sevoflurane anesthesia administration.

Adolescent↗

Retinal ganglion cell coding in simulated active vision.

The image on the retina is almost never static. Eye, head, and body movements, and externally generated motion create rapid and continual changes in the retinal image ("active vision"). Virtually all vision in animals such as primates, which make saccades as often as 3-4 times/s, is based on information that must be derived from the first few hundred milliseconds after sudden, global changes in the retinal image. These changes may be accompanied by large changes in area mean luminance, as well as higher order image contrast statistics. This study investigated how retinal ganglion cell responses, whose response properties have been typically studied and defined in a stable stimulus regime, are affected by sudden changes in mean luminance that are characteristic of active vision. Specifically, the steady-state responses of retinal ganglion cells to static or moving square-wave grating stimuli were recorded in an isolated, superfused rabbit eyecup preparation and compared to responses after saccade-like changes in luminance. The manner of coding after luminance changes was different for different ganglion cell classes; both suppression and enhancement of responses to patterns following luminance changes were found. Brisk-transient Off cells unambiguously signaled the darkening of the overall image, but were also modulated by the subsequently appearing grating stimulus. Several types of On-center cell behavior were observed, ranging from strong suppression of the subsequent response by luminance changes, to strong enhancement. Overall, most ganglion cells distinguished static patterns after a luminance change via differences in their spike discharges nearly as well as before, although there were clear asymmetries between the On and Off pathways. Changes in mean luminance in some ganglion cells, such as On-Off directionally selective ganglion cells, could create large phase shifts in the response to patterned, moving stimuli, although these stimuli were still detected immediately after luminance changes. The results of this study show that the image dynamics of active vision may be a fundamental challenge for the visual system because of strong effects on retinal ganglion cell function. However, rapid extraction of unambiguous information after luminance changes appears to be encoded in differences in the spike discharges in different retinal ganglion cell classes. Asymmetries among ganglion cell classes in sensitivity to luminance changes may provide a basis by which some provide the "context" for interpreting the firing of others.

Animals↗

Parasympathetic heart rate modulation during parabolic flights.

During parabolic flight short periods of microgravity and hypergravity are created. These changes influence cardiovascular function differently according to posture. During the 29th parabolic flight campaign of the European Space Agency (ESA), the electrocardiogram (ECG) was recorded continuously in seven healthy volunteers in two positions (standing and supine). Five different phases were differentiated: 1 g (1 g=9.81 m/s(2)) before and after each parabola, 1.8 g at the ascending leg of the parabola (hypergravity), 0 g at the apex, 1.6 g at the descending leg (hypergravity). We assessed heart rate variability (HRV) by indices of temporal analysis [mean RR interval (meanRR), the standard deviation of the intervals (SDRR), and the square root of the mean squared differences of successive intervals (rMSSD) and coefficient of variation (CV)]. In the supine position no significant differences were shown between different gravity phases for all HRV indices. In the standing position the 0 g phase showed a tendency towards higher values of meanRR compared to the control and to the other phases ( p=NS). SDRR, rMSSD and CV were significantly higher compared to control ( p<0.05). Significantly higher values for meanRR in the supine position at 1 g and hypergravity ( p<0.05) were found when compared to standing. SDRR was significantly higher at 0 g in the standing position compared to supine [95 (44) ms vs. 50 (15) ms; p<0.05] and lower in other phases. rMSSD and CV showed the same trend ( p=NS). We confirm that, during parabolic flights, position matters for cardiovascular measurements. Time domain indices of HRV during different gravity phases showed: (1) higher vagal modulation of the autonomic nervous system in microgravity, when compared with normo- or hypergravity in standing subjects; and (2) no differences in supine subjects between different g phases.

Adaptation, Physiological↗

Bridging the Quantum gap: attaining adequacy utilizing the Quantum night-time exchange device.

BACKGROUND: The advent of night-time exchange devices (NXDs), such as the Quantum, gives the client on home peritoneal dialysis the option of five exchanges well spaced in a day or, for those who need only four exchanges a day, the ability to change their long dwell to the daytime. PURPOSE: To ascertain whether we were able to attain the NKF-DOQI recommended Kt/V of 2.0 for CAPD clients by adding a fifth exchange utilizing the Quantum NXD or by introducing a long daytime dwell for clients who only needed four exchanges per day. We also looked at alternative uses for a NXD. METHOD: As part of our CQI process for all clients on home peritoneal dialysis, dialysis adequacy testing is performed two weeks after the start of full prescription and biannually thereafter. In this study, the first group of clients, the "lifestyle group", changed to using the NXD to allow more daytime freedom. This first group had repeated 24 hour dialysate collections to ensure they maintained adequate Kt/Vs. The second group of clients, the "adequacy group", had Kt/Vs falling below the NKF-DOQI recommendation of 2.0. This second group had their peritoneal dialysis prescription optimized utilizing a computer modeling program. Their prescription was then changed accordingly Two weeks after the change in prescription, 24 hour dialysate collections were repeated for each client to ensure the new Kt/Vs were within the predicted parameters. RESULTS CONCLUSIONS: We were able to attain the NKF-DOQI recommended Kt/V, utilizing the CANUSA recommended fill volumes, for all clients underdialyzed on CAPD through the addition of a fifth exchange using the NXD. Other clients who may benefit from the use of NXDs are those who need more daytime freedom.

Adult↗