Measurement of limb venous compliance in humans: technical considerations and physiological findings.

We conducted a series of studies to develop and test a rapid, noninvasive method to measure limb venous compliance in humans. First, we measured forearm volume (mercury-in-Silastic strain gauges) and antecubital intravenous pressure during inflation of a venous collecting cuff around the upper arm. Intravenous pressure fit the regression line, -0.3 +/- 0.7 + 0.95 +/- 0.02. cuff pressure (r = 0.99 +/- 0.00), indicating cuff pressure is a good index of intravenous pressure. In subsequent studies, we measured forearm and calf venous compliance by inflating the venous collecting cuff to 60 mmHg for 4 min, then decreasing cuff pressure at 1 mmHg/s (over 1 min) to 0 mmHg, using cuff pressure as an estimate of venous pressure. This method produced pressure-volume curves fitting the quadratic regression (Deltalimb volume) = beta(0) + beta(1). (cuff pressure) + beta(2). (cuff pressure)(2), where Delta is change. Curves generated with this method were reproducible from day to day (coefficient of variation: 4.9%). In 11 subjects we measured venous compliance via this method under two conditions: with and without (in random order) superimposed sympathetic activation (ischemic handgrip exercise to fatigue followed by postexercise ischemia). Calf and forearm compliance did not differ between control and sympathetic activation (P > 0.05); however, the data suggest that unstressed volume was reduced by the maneuver. These studies demonstrate that venous pressure-volume curves can be generated both rapidly and noninvasively with this technique. Furthermore, the results suggest that although whole-limb venous compliance is under negligible sympathetic control in humans, unstressed volume can be affected by the sympathetic nervous system.     

Unconfined compression of articular cartilage: nonlinear behavior and comparison with a fibril-reinforced biphasic model

Mechanical behavior of articular cartilage was characterized in unconfined compression to delineate regimes of linear and nonlinear behavior, to investigate the ability of a fibril-reinforced biphasic model to describe measurements, and to test the prediction of biphasic and poroelastic models that tissue dimensions alter tissue stiffness through a specific scaling law for time and frequency. Disks of full-thickness adult articular cartilage from bovine humeral heads were subjected to successive applications of small-amplitude ramp compressions cumulating to a 10 percent compression offset where a series of sinusoidal and ramp compression and ramp release displacements were superposed. We found all equilibrium behavior (up to 10 percent axial compression offset) to be linear, while most nonequilibrium behavior was nonlinear, with the exception of small-amplitude ramp compressions applied from the same compression offset. Observed nonlinear behavior included compression-offset-dependent stiffening of the transient response to ramp compression, nonlinear maintenance of compressive stress during release from a prescribed offset, and a nonlinear reduction in dynamic stiffness with increasing amplitudes of sinusoidal compression. The fibril-reinforced biphasic model was able to describe stress relaxation response to ramp compression, including the high ratio of peak to equilibrium load. However, compression offset-dependent stiffening appeared to suggest strain-dependent parameters involving strain-dependent fibril network stiffness and strain-dependent hydraulic permeability. Finally, testing of disks of different diameters and rescaling of the frequency according to the rule prescribed by current biphasic and poroelastic models (rescaling with respect to the sample's radius squared) reasonably confirmed the validity of that scaling rule. The overall results of this study support several aspects of current theoretical models of articular cartilage mechanical behavior, motivate further experimental characterization, and suggest the inclusion of specific nonlinear behaviors to models.     

Sex-related effects on venous compliance and capillary filtration in the lower limb

Recent studies in humans have suggested sex differences in venous compliance of the lower limb, with lower compliance in women. Capillary fluid filtration could, however, be a confounder in the evaluation of venous compliance. The venous capacitance and capillary filtration response in the calves of 12 women (23.2 +/- 0.5 years) and 16 men (22.9 +/- 0.5 years) were studied during 8 min lower body negative pressure (LBNP) of 11, 22, and 44 mmHg. Calf venous compliance is dependent on pressure and was determined using the first derivative of a quadratic regression equation that described the capacitance-pressure relationship [compliance = beta1 + (2 x beta2 x transmural pressure)]. We found a lower venous compliance in women at low transmural pressures, and the venous capacitance in men was increased (P < 0.05). However, the difference in compliance between sexes was reduced and not seen at higher transmural pressures. Net capillary fluid filtration and capillary filtration coefficient (CFC) were greater in women than in men during LBNP (P < 0.05). Furthermore, calf volume increase (capacitance response + total capillary filtration) during LBNP was equivalent in both sexes. When total capillary filtration was not subtracted from the calf capacitance response in the calculation of venous compliance, the sex differences disappeared, emphasizing that venous compliance measurement should be corrected for the contribution of CFC.     

Asynchronous exponential growth for a two-phase size-structured population model and comparison with the corresponding one-phase model

In this paper we study a two-phase size-structured population model with distributed delay in the birth process. This model distinguishes individuals by ‘active’ or ‘resting’ status. The individuals in the two life-stages have different growth rates. Only individuals in the ‘active’ stage give birth to the individuals in the ‘active’ stage or the ‘resting’ stage. The size of all the newborns is 0. By using the method of semigroups, we obtain that the model is globally well-posed and its solution possesses the property of asynchronous exponential growth. Moreover, we give a comparison between this two-phase model with the corresponding one-phase model and show that the asymptotic behaviours of the sum of the densities of individuals in the ‘active’ stage and the ‘resting’ stage and the solution of the corresponding one-phase model are different.     

A comparison of cartilage stress-relaxation models in unconfined compression: QLV and stretched exponential in combination with fluid flow

Cartilage exhibits nonlinear viscoelastic behaviour. Various models have been proposed to explain cartilage stress relaxation, but it is unclear whether explicit modelling of fluid flow in unconfined compression is needed. This study compared Fung's quasi-linear viscoelastic (QLV) model with a stretched-exponential model of cartilage stress relaxation and examined each of these models both alone and in combination with a fluid-flow model in unconfined compression. Cartilage explants were harvested from bovine calf patellofemoral joints and equilibrated in tissue culture for 5 days before stress-relaxation testing in unconfined compression at 5% nominal strain. The stretched exponential models fit as well as the QLV models. Furthermore, the average stretched exponential relaxation time determined by this model lies within the range of experimentally measured relaxation times for extracted proteoglycan aggregates, consistent with the hypothesis that the stretched exponential model represents polymeric mechanisms of cartilage viscoelasticity.     

The exponential model for a regulatory enzyme. An interpretation of the linear free-energy relationship.

A physical mechanism is suggested to explain the linear free-energy relationship employed in the exponential model for a regulatory enzyme [Ainsworth (1977) J. Theor. Biol. 68, 391-413]. The interpretation depends on the assumption that the structure of the enzyme changes in proportion to its saturation by substrate but at a rate that is low compared with the rates of the association-dissociation reactions of the enzyme-substrate system.     

Prediction in censored survival data: a comparison of the proportional hazards and linear regression models.

Although the analysis of censored survival data using the proportional hazards and linear regression models is common, there has been little work examining the ability of these estimators to predict time to failure. This is unfortunate, since a predictive plot illustrating the relationship between time to failure and a continuous covariate can be far more informative regarding the risk associated with the covariate than a Kaplan-Meier plot obtained by discretizing the variable. In this paper the predictive power of the Cox (1972, Journal of the Royal Statistical Society, Series B 34, 187-202) proportional hazards estimator and the Buckley-James (1979, Biometrika 66, 429-436) censored regression estimator are compared. Using computer simulations and heuristic arguments, it is shown that the choice of method depends on the censoring proportion, strength of the regression, the form of the censoring distribution, and the form of the failure distribution. Several examples are provided to illustrate the usefulness of the methods.     

Sexual mixing models: a comparison of analogue deterministic and stochastic models.

Models for sexual partner choice are discussed for the case of highly variable sexual activity in the population. It is demonstrated that the variances in the number of infected persons may be extremely large. For the random mixing model, higher order cumulants are also evaluated. On the basis of these results the applicability of deterministic models and models for expectations only are questioned. A general model is proposed for handling nonrandom, or correlated, mixing. The problem of inconsistency is overcome by considering the couples having sex as the natural unit in the model. In the case of s discrete homogeneous groups it is shown that only (s2) parameters defining the interaction between the groups can be chosen freely. Finally, the effect of correlation in partner choice is demonstrated by a bivariate lognormal model for partner choice.     

Decreased capillary filtration but maintained venous compliance in the lower limb of aging women

There are sex-related differences in venous compliance and capillary filtration in the lower limbs, which to some extent can explain the susceptibility to orthostatic intolerance in young women. With age, venous compliance and capacitance are reduced in men. This study was designed to evaluate age-related changes in venous compliance and capillary filtration in the lower limbs of healthy women. Included in this study were 22 young and 12 elderly women (23.1 +/- 0.4 and 66.4 +/- 1.4 yr). Lower body negative pressure (LBNP) of 11, 22, and 44 mmHg created defined transmural pressure gradients in the lower limbs. A plethysmographic technique was used on the calf to assess venous capacitance and net capillary filtration. Venous compliance was calculated with the aid of a quadratic regression equation. No age-related differences in venous compliance and capacitance were found. Net capillary filtration and capillary filtration coefficient (CFC) were lower in elderly women at a LBNP of 11 and 22 mmHg (0.0032 vs. 0.0044 and 0.0030 vs. 0.0041 ml.100 ml(-1).min(-1).mmHg(-1), P < 0.001). At higher transmural pressure (LBNP, 44 mmHg), CFC increased by approximately 1/3 (0.010 ml.100 ml(-1).min(-1).mmHg(-1)) in the elderly (P < 0.001) but remained unchanged in the young women. In conclusion, no age-related decrease in venous compliance and capacitance was seen in women. However, a decreased CFC was found with age, implying reduced capillary function. Increasing transmural pressure increased CFC in the elderly women, indicating an increased capillary susceptibility to transmural pressure load in dependent regions. These findings differ from earlier studies on age-related effects in men, indicating sex-specific vascular aging both in the venous section and microcirculation.     

Fabrication of elastomer arterial models with specified compliance.

A simple way of making elastic tubes using a mechanical lathe for precise control of the wall thickness is proposed in this study. These tubes are particularly useful for modeling properties of large arteries. Tubes with different geometric parameters and hence different elastic behavior have been made with a silicon elastomer (Rhodorsil RTV 1556). They have been created to be used for compliance measurements in hemodynamics research. Within a limited range of pressures, depending on the wall thickness, such tubes can be used to study models in which the compliance value is assumed to be constant.     

Decreased venous compliance in dogs with chronic renal hypertension.

Femoral vein (FV) pressure-volume relationships were measured in vitro in 14 dogs with chronic (more than 4 weeks), one-kidney perinephritic hypertension and in 13 unilaterally nephrectomized normotensive control dogs. Segments of FV were also examined histologically and analyzed for their water and electrolyte contents. Compared to controls: (I) the FV pressure-volume curves of hypertensive dogs were shifted toward the pressure axis (P is less than 0.05); (ii) calcaulated vagous compliance in the pressure range of 0-15 mm Hg was decreased (P is less than 0.05); and (iii) the water and sodium contents of vwins from hypertensive dogs were increased (P is less than 0.05). Histological examination of the FV from hypertensive and control dogs did not reveal significant differences. The findings indicate that the decreases in venous compliance that we have previously observed in the early stages (less than 4 weeks) of perinephritic hypertension in dogs persist into the chronic stage of hypertension. Venous wall "edema" may account for the decreased venous compliance in this form of hypertension.     

Mechanisms of cardiac cell excitation with premature monophasic and biphasic field stimuli: a model study.

The mechanisms by which extracellular electric field stimuli induce the (re)excitation of cardiac cells in various stages of refractoriness are still not well understood. We modeled the interactions between an isolated cardiac cell and imposed extracellular electric fields to determine the mechanisms by which relatively low-strength uniform monophasic and biphasic field stimuli induce premature reexcitations. An idealized ventricular cell was simulated with 11 subcellular membrane patches, each of which obeyed Luo-Rudy (phase 1) kinetics. Implementing a standard S1-S2 pulse protocol, strength-interval maps of the cellular excitatory responses were generated for rectangular monophasic and symmetric biphasic field stimuli of 2, 5, 10, and 20 ms total duration. In contrast to previously documented current injection studies, our results demonstrate that a cardiac cell exhibits a significantly nonmonotonic excitatory response to premature monophasic and, to a much lesser degree, biphasic field stimuli. Furthermore, for monophasic stimuli at low field strengths, the cell is exquisitely sensitive to the timing of the shock, demonstrating a classic all-or-none depolarizing response. However, at higher field strengths this all-or-none sensitivity reverts to a more gradual transition of excitatory responses with respect to stimulus prematurity. In contrast, biphasic stimuli produce such graded responses at all suprathreshold stimulus strengths. Similar behaviors are demonstrated at all S2 stimulus durations tested. The generation of depolarizing (sodium) currents is triggered by one or more of the sharp field gradient changes produced at the stimulus edges-i.e., make, break, and transphasic (for biphasic stimuli)-with the magnitude of these edge-induced current contributions dependent on both the prematurity and the strength of the applied field. In all cases, however, depolarizing current arises from the partial removal of sodium inactivation from at least part of the cell, because of either the natural process of repolarization or a localized acceleration of this process by the impressed field.     

Carcass conformation and fat cover scores in beef cattle: A comparison of threshold linear models vs grouped data models

Background

Beef carcass conformation and fat cover scores are measured by subjective grading performed by trained technicians. The discrete nature of these scores is taken into account in genetic evaluations using a threshold model, which assumes an underlying continuous distribution called liability that can be modelled by different methods.

Methods

Five threshold models were compared in this study: three threshold linear models, one including slaughterhouse and sex effects, along with other systematic effects, with homogeneous thresholds and two extensions with heterogeneous thresholds that vary across slaughterhouses and across slaughterhouse and sex and a generalised linear model with reverse extreme value errors. For this last model, the underlying variable followed a Weibull distribution and was both a log-linear model and a grouped data model. The fifth model was an extension of grouped data models with score-dependent effects in order to allow for heterogeneous thresholds that vary across slaughterhouse and sex. Goodness-of-fit of these models was tested using the bootstrap methodology. Field data included 2,539 carcasses of the Bruna dels Pirineus beef cattle breed.

Results

Differences in carcass conformation and fat cover scores among slaughterhouses could not be totally captured by a systematic slaughterhouse effect, as fitted in the threshold linear model with homogeneous thresholds, and different thresholds per slaughterhouse were estimated using a slaughterhouse-specific threshold model. This model fixed most of the deficiencies when stratification by slaughterhouse was done, but it still failed to correctly fit frequencies stratified by sex, especially for fat cover, as 5 of the 8 current percentages were not included within the bootstrap interval. This indicates that scoring varied with sex and a specific sex per slaughterhouse threshold linear model should be used in order to guarantee the goodness-of-fit of the genetic evaluation model. This was also observed in grouped data models that avoided fitting deficiencies when slaughterhouse and sex effects were score-dependent.

Conclusions

Both threshold linear models and grouped data models can guarantee the goodness-of-fit of the genetic evaluation for carcass conformation and fat cover, but our results highlight the need for specific thresholds by sex and slaughterhouse in order to avoid fitting deficiencies.     

光响应曲线的指数改进模型与常用模型比较

光响应曲线的参数是研究植物生理状态的重要指标, 常用的光响应曲线模型无法准确地计算出光饱和点和最大净光合速率。该文利用光响应曲线新模型——指数改进模型、直角双曲线模型、直角双曲线修正模型、非直角双曲线模型和指数模型, 拟合高粱(Sorghum bicolor)、苋(Amaranthus tricolor)、大麦(Hordeum vulgare)和半夏(Pinellia ternata)的光响应曲线, 并随机选取部分数据进行检验, 得到了各模型计算出的主要生理参数, 并对这些数据进行了比较分析, 讨论了各模型之间的优缺点和准确性, 描述了C₃、C₄植物光响应的适宜性。结果表明, 基于C₃植物得到的指数改进模型和直角双曲线修正模型能较准确地计算出C₃、C₄植物饱和光强和最大净光合速率, 并在描述光响应曲线时比另外3个模型具有更高的精确性和适宜性。实验结果可为光响应曲线模型在C₃和C₄光合途径植物中的应用提供参考。     

A comparison study of models and fitting procedures for biphasic viral dynamics in HIV-1 infected patients treated with antiviral therapies

The study of HIV dynamics is one of the most important developments in recent AIDS research. It has led to a new understanding of the pathogenesis of HIV infection. But, although important findings in HIV dynamics have been published in prestigious scientific journals in the last 5 years, the model-fitting procedures used in these publications have not been studied in any detail. In this paper, we evaluate the performance of four model-fitting procedures proposed and used in biphasic HIV dynamic data analysis via extensive Monte Carlo simulations. We propose some guidelines for practitioners to select an appropriate method for their own data analysis. Real data examples from an AIDS clinical trial are provided as illustrations.