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991.
A semiparametric estimate of an average regression effect with right-censored failure time data has recently been proposed under the Cox-type model where the regression effect beta(t) is allowed to vary with time. In this article, we derive a simple algebraic relationship between this average regression effect and a measurement of group differences in k-sample transformation models when the random error belongs to the G(rho) family of Harrington and Fleming (1982, Biometrika 69, 553-566), the latter being equivalent to the conditional regression effect in a gamma frailty model. The models considered here are suitable for the attenuating hazard ratios that often arise in practice. The results reveal an interesting connection among the above three classes of models as alternatives to the proportional hazards assumption and add to our understanding of the behavior of the partial likelihood estimate under nonproportional hazards. The algebraic relationship provides a simple estimator under the transformation model. We develop a variance estimator based on the empirical influence function that is much easier to compute than the previously suggested resampling methods. When there is truncation in the right tail of the failure times, we propose a method of bias correction to improve the coverage properties of the confidence intervals. The estimate, its estimated variance, and the bias correction term can all be calculated with minor modifications to standard software for proportional hazards regression. 相似文献
992.
993.
Within-cluster resampling 总被引:1,自引:0,他引:1
994.
Hierarchical likelihood approach for frailty models 总被引:5,自引:0,他引:5
995.
996.
997.
The use of cryosurgery in the treatment of uterine fibroids is emerging as a possible treatment modality. The two known mechanisms of direct cell injury during the tissue freezing process are linked to intracellular ice formation and cellular dehydration. These processes have not been quantified within uterine fibroid tumor tissue. This study reports the use of a combination of freeze-substitution microscopy and differential scanning calorimetry (DSC) to quantify freeze-induced dehydration within uterine fibroid tumor tissue. Stereological analysis of histological tumor sections was used to obtain the initial cellular volume (V(o)) or the Krogh model dimensions (deltaX, the distance between the microvascular channels = 15.5 microm, r(vo), the initial radius of the extracellular space = 4.8 micro m, and L, the axial length of the Krogh cylinder = 19.1 microm), the interstitial volume ( approximately 23%), and the vascular volume ( approximately 7%) of the fibroid tumor tissue. A Boyle-van't Hoff plot was then constructed by examining freeze-substituted micrographs of "equilibrium"-cooled tissue slices to obtain the osmotically inactive cell volume, V(b) = 0.47V(o). The high interstitial volume precludes the use of freeze-substitution microscopy data to quantify freeze-induced dehydration. Therefore, a DSC technique, which does not suffer from this artifact, was used to obtain the water transport data. A model of water transport was fit to the calorimetric data at 5 and 20 degrees C/min to obtain the "combined best fit" membrane permeability parameters of the embedded fibroid tumor cells, assuming either a Krogh cylinder geometry, L(pg) = 0.92 x 10(-13) m(3)/Ns (0.55 microm/min atm) and E(Lp) = 129.3 kJ/mol (30.9 kcal/mol), or a spherical cell geometry (cell diameter = 18.3 microm), L(pg) = 0.45 x 10(-13) m(3)/Ns (0.27 microm/min atm) and E(Lp) = 110.5 kJ/mol (26.4 kcal/mol). In addition, numerical simulations were performed to generate conservative estimates, in the absence of ice nucleation between -5 and -30 degrees C, of intracellular ice volume in the tumor tissue at various cooling rates typical of those experienced during cryosurgery (< or =100 degrees C/min). With this assumption, the Krogh model simulations showed that the fibroid tumor tissue cells cooled at rates < or = 50 degrees C/min are essentially dehydrated; however, at rates >50 degrees C/min the amount of water trapped within the tissue cells increases rapidly with increasing cooling rate, suggesting the formation of intracellular ice. 相似文献
998.
The probability that beneficial mutations are lost in populations with periodic bottlenecks 总被引:9,自引:0,他引:9
Population bottlenecks affect the dynamics of evolution, increasing the probability that beneficial mutations will be lost. Recent protocols for the experimental study of evolution involve repeated bottlenecks-when fresh media are inoculated during serial transfer or when chemostat tubes are changed. Unlike population reductions caused by stochastic environmental factors, these bottlenecks occur at known, regular intervals and with a fixed dilution ratio. We derive the ultimate probability of extinction for a beneficial mutation in a periodically bottlenecked population, using both discrete and continuous approaches. We show that both approaches yield the same approximation for extinction probability. From this, we derive an approximate expression for an effective population size. 相似文献
999.
In a recent paper, Tuckwell and Le Corfec [J. Theor. Biol. 195 (1998) 450-463] applied the multi-dimensional diffusion process to model early human immunodeficiency virus type-1 (HIV-1) population dynamics. The purpose of this paper is to assess certain features and consequences of their model in the context of Tan and Wu's stochastic approach [Math. Biosci. 147 (1998) 173-205]. 相似文献
1000.
Doebler JA 《Cell biology and toxicology》1999,15(5):279-289
Studies were conducted using a novel in vitro approach to investigate the efficacy of acetamidine hydrochloride (ACE) and guanidine hydrochloride (GUAN), previously shown to block gramicidin D (GRAM) channels in artificial membranes, in preventing the toxic effects of GRAM in NG108-15 (neuroblastoma×glioma hybrid) cells. Specifically, intracellular microelectrode techniques were employed to examine changes in membrane resting potential (V
m) and input resistance (R
in). At 1 mol/L, ACE significantly reduced loss of V
m induced by 1 or 10 g/ml GRAM, although higher concentrations of ACE did not afford enhanced antagonism. GUAN, in contrast, produced a concentration-dependent antagonism of GRAM-induced V
m and R
in loss, with high concentrations (10 or 100 mol/L) completely preventing diminutions in both V
m and R
in. In control cells superfused without GRAM, ACE produced a direct, concentration-dependent reduction in V
m and R
in, whereas GUAN hyperpolarized NG108-15 cells but did not alter R
in. These data represent the initial demonstration of the reversal of GRAM toxicity in an intact cell system. 相似文献