Correcting Inhomogeneity of Variance with Power Transformation Weighting

Box, George E. P.; Hill, William J.

doi:10.2307/1267668

Cited by 52 publications

(25 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Data were analyzed by one-way analysis of variance (ANOVA) followed by Tukey's honestly significant difference post hoc test. When necessary, transformations were performed to ensure that variances were homogeneous among groups and that the residuals of the one-way analysis of variance model followed a Gaussian (normal) distribution (Box and Cox, 1964;Box and Hill, 1974). For the tissue distribution study, concentrations of LGD-3303 in the ventral prostate and levator ani were compared by two-tailed paired Student's t test.…”

Section: Compoundsmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of LGD-3303 [9-Chloro-2-ethyl-1-methyl-3-(2,2,2-trifluoroethyl)-3H-pyrrolo-[3,2-f]quinolin-7(6H)-one], an Orally Available Nonsteroidal-Selective Androgen Receptor Modulator

Vajda¹,

López²,

Rix³

et al. 2008

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Selective androgen receptor modulators (SARMs) are a new class of molecules in development to treat a variety of diseases. SARMs maintain the beneficial effects of androgens, including increased muscle mass and bone density, while having reduced activity on unwanted side effects. The mechanisms responsible for the tissue-selective activity of SARMs are not fully understood, and the pharmacokinetic (PK)/pharmacodynamic (PD) relationships are poorly described. Tissue-specific compound distribution potentially could be a mechanism responsible for apparent tissue selectivity. We examined the PK/PD relationship of a novel SARM, LGD-3303 [9-chloro-2-ethyl-1-methyl-3-(2,2,2-trifluoroethyl)-3H-pyrrolo[3,2-f]quinolin-7(6H)-one], in a castrated rat model of androgen deficiency.LGD-3303 has potent activity on levator ani muscle but is a partial agonist on the preputial gland and ventral prostate.LGD-3303 never stimulated ventral prostate above intact levels despite increasing plasma concentrations of compound. Tissue-selective activity was maintained when LGD-3303 was dosed orally or by continuous infusion, two routes of administration with markedly different time versus exposure profiles. Despite the greater muscle activity relative to prostate activity, local tissue concentrations of LGD-3303 were higher in the prostate than in the levator ani muscle.LGD-3303 has SARM properties that are independent of its pharmacokinetic profile, suggesting that the principle mechanism for tissue-selective activity is the result of altered molecular interactions at the level of the androgen receptor.

show abstract

Section: Compoundsmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of LGD-3303 [9-Chloro-2-ethyl-1-methyl-3-(2,2,2-trifluoroethyl)-3H-pyrrolo-[3,2-f]quinolin-7(6H)-one], an Orally Available Nonsteroidal-Selective Androgen Receptor Modulator

Vajda¹,

López²,

Rix³

et al. 2008

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…Let the m × 1 residual vector be given by (4) Let the sum of squares of weighted residuals SSR(θ) be denoted by (5) The Jacobian matrix is defined as ∂f(θ,x)/∂θ in its continuous form, but requires redefinition where numerical derivatives requires taking a finite step in θ. Therefore, the sensitivity matrix S(θ) is defined with components (6) and is an approximation of the Jacobian matrix, where I j is the jth column of a p × p identity matrix, and h ij is the step size or mesh spacing for jth parameter and ith observation.…”

Section: Notationmentioning

confidence: 99%

SENSOP: A derivative-free solver for nonlinear least squares with sensitivity scaling

1993

View full text Add to dashboard Cite

Nonlinear least squares optimization is used most often in fitting a complex model to a set of data. An ordinary nonlinear least squares optimizer assumes a constant variance for all the data points. This paper presents SENSOP, a weighted nonlinear least squares optimizer, which is designed for fitting a model to a set of data where the variance may or may not be constant. It uses a variant of the Levenberg-Marquardt method to calculate the direction and the length of the step change in the parameter vector. The method for estimating appropriate weighting functions applies generally to 1-dimensional signals and can be used for higher dimensional signals. Sets of multiple tracer outflow dilution curves present special problems because the data encompass three to four orders of magnitude; a fractional power function provides appropriate weighting giving success in parameter estimation despite the wide range.

show abstract

“…Important applications of variance functions include, but not limited to, description of volatility or risk in a stock market and identification of homoscedastic transformations in regression. For more classical applications of variance functions, one can refer to Box and Hill (1974), Box and Meyer (1986), Carroll and Ruppert (1988), Davidian, Carroll and Smith (1988), Davidian and Carroll (1987). In the recent study of social inequality (Western and Bloome, 2009), variance function estimation is the main quantity to characterize the income insecurity.…”

Section: Introductionmentioning

confidence: 99%

Semiparametric Estimation and Inference of Variance Function with Large Dimensional Covariates

Zhu

2019

STAT SINICA

View full text Add to dashboard Cite

We investigate the simultaneous estimation and inference of the central mean subspace and central variance subspace to reduce the effective number of covariates that predict respectively the mean and variability of the response variable. We study the estimation, inference and efficiency properties under different scenarios, and further propose a class of locally efficient estimators when the truly efficient estimator is not practically available. This partially explains the necessity of some dimension-reduction assumptions which were commonly imposed on the conditional mean function in estimating the central variance subspace. Comprehensive simulation studies and a real-data analysis are performed to demonstrate the finite sample performance and efficiency gain of the locally efficient estimators in comparison with existing estimation procedures.

show abstract

Correcting Inhomogeneity of Variance with Power Transformation Weighting

Cited by 52 publications

References 0 publications

Pharmacokinetics and Pharmacodynamics of LGD-3303 [9-Chloro-2-ethyl-1-methyl-3-(2,2,2-trifluoroethyl)-3H-pyrrolo-[3,2-f]quinolin-7(6H)-one], an Orally Available Nonsteroidal-Selective Androgen Receptor Modulator

Pharmacokinetics and Pharmacodynamics of LGD-3303 [9-Chloro-2-ethyl-1-methyl-3-(2,2,2-trifluoroethyl)-3H-pyrrolo-[3,2-f]quinolin-7(6H)-one], an Orally Available Nonsteroidal-Selective Androgen Receptor Modulator

SENSOP: A derivative-free solver for nonlinear least squares with sensitivity scaling

Semiparametric Estimation and Inference of Variance Function with Large Dimensional Covariates

Contact Info

Product

Resources

About