3,420 research outputs found
Estimation of nonparametric regression models with a mixture of Berkson and classical errors
postprin
The nested dirichlet distribution and incomplete categorical data analysis
The nested Dirichlet distribution (NDD) is an important distribution defined on the closed n-dimensional simplex. It includes the classical Dirichlet distribution and is useful in incomplete categorical data (ICD) analysis. In this article, we develop the distributional properties of NDD. New large-sample likelihood and small-sample Bayesian approaches for analyzing ICD are proposed and compared with existing likelihood/Bayesian strategies. We show that the new approaches have at least three advantages over existing approaches based on the traditional Dirichlet distribution in both frequentist and conjugate Bayesian inference for ICD. The new methods possess closed-form expressions for both the maximum likelihood and Bayes estimates when the likelihood function is in NDD form; produce computationally efficient EM and data augmentation algorithms when the likelihood is not in NDD form; and provide exact sampling procedures for some special cases. The methodologies are illustrated with simulated and real data.published_or_final_versio
Further properties and new applications of the nested Dirichlet distribution
Recently, Ng et al. (2009) studied a new family of distributions, namely the nested Dirichlet distributions. This family includes the traditional Dirichlet distribution as a special member and can be adopted to analyze incomplete categorical data. However, other important aspects of the family, such as marginal and conditional distributions and related properties are not yet available in the literature. Moreover, diverse applications of the family to the real world need to be further explored. In this paper, we first obtain the marginal and conditional distributions and other related properties of the nested Dirichlet distribution. We then present new applications of the family in fitting competing-risks model, analyzing incomplete categorical data and evaluating cancer diagnosis tests. Three real data involving failure times of radio transmitter receivers, attitude toward the death penalty and ultrasound ratings for breast cancer metastasis are provided. © 2009 Elsevier B.V. All rights reserved.postprin
Confidence-interval construction for rate ratio in matched-pair studies with incomplete data
Matched-pair design is often used in clinical trials to increase the efficiency of establishing equivalence between two treatments with binary outcomes. In this article, we consider such a design based on rate ratio in the presence of incomplete data. The rate ratio is one of the most frequently used indices in comparing efficiency of two treatments in clinical trials. In this article, we propose 10 confidence-interval estimators for the rate ratio in incomplete matched-pair designs. A hybrid method that recovers variance estimates required for the rate ratio from the confidence limits for single proportions is proposed. It is noteworthy that confidence intervals based on this hybrid method have closed-form solution. The performance of the proposed confidence intervals is evaluated with respect to their exact coverage probability, expected confidence interval width, and distal and mesial noncoverage probability. The results show that the hybrid Agresti–Coull confidence interval based on Fieller’s theorem performs satisfactorily for small to moderate sample sizes. Two real examples from clinical trials are used to illustrate the proposed confidence intervals.postprin
The absolute position of a resonance peak
It is common practice in scattering theory to correlate between the position
of a resonance peak in the cross section and the real part of a complex energy
of a pole of the scattering amplitude. In this work we show that the resonance
peak position appears at the absolute value of the pole's complex energy rather
than its real part. We further demonstrate that a local theory of resonances
can still be used even in cases previously thought impossible
Dirichlet composition distribution for compositional data with zero components: An application to fluorescence in situ hybridization (FISH) detection of chromosome
Copyright © 2021 The Authors. Zeros in compositional data are very common and can be classified into rounded and essential zeros. The rounded zero refers to a small proportion or below detection limit value, while the essential zero refers to the complete absence of the component in the composition. In this article, we propose a new framework for analyzing compositional data with zero entries by introducing a stochastic representation. In particular, a new distribution, namely the Dirichlet composition distribution, is developed to accommodate the possible essential-zero feature in compositional data. We derive its distributional properties (e.g., its moments). The calculation of maximum likelihood estimates via the Expectation-Maximization (EM) algorithm will be proposed. The regression model based on the new Dirichlet composition distribution will be considered. Simulation studies are conducted to evaluate the performance of the proposed methodologies. Finally, our method is employed to analyze a dataset of fluorescence in situ hybridization (FISH) for chromosome detection.National Natural Science Foundation of China. Grant Numbers: 12171167, 11801184; Research Grant Council of the Hong Kong Special Administrative Region. Grant Numbers: UGC/FDS14/P06/17, UGC/FDS14/P02/18
A critical evaluation of network and pathway based classifiers for outcome prediction in breast cancer
Recently, several classifiers that combine primary tumor data, like gene
expression data, and secondary data sources, such as protein-protein
interaction networks, have been proposed for predicting outcome in breast
cancer. In these approaches, new composite features are typically constructed
by aggregating the expression levels of several genes. The secondary data
sources are employed to guide this aggregation. Although many studies claim
that these approaches improve classification performance over single gene
classifiers, the gain in performance is difficult to assess. This stems mainly
from the fact that different breast cancer data sets and validation procedures
are employed to assess the performance. Here we address these issues by
employing a large cohort of six breast cancer data sets as benchmark set and by
performing an unbiased evaluation of the classification accuracies of the
different approaches. Contrary to previous claims, we find that composite
feature classifiers do not outperform simple single gene classifiers. We
investigate the effect of (1) the number of selected features; (2) the specific
gene set from which features are selected; (3) the size of the training set and
(4) the heterogeneity of the data set on the performance of composite feature
and single gene classifiers. Strikingly, we find that randomization of
secondary data sources, which destroys all biological information in these
sources, does not result in a deterioration in performance of composite feature
classifiers. Finally, we show that when a proper correction for gene set size
is performed, the stability of single gene sets is similar to the stability of
composite feature sets. Based on these results there is currently no reason to
prefer prognostic classifiers based on composite features over single gene
classifiers for predicting outcome in breast cancer
Bridging Time Scales in Cellular Decision Making with a Stochastic Bistable Switch
Cellular transformations which involve a significant phenotypical change of
the cell's state use bistable biochemical switches as underlying decision
systems. In this work, we aim at linking cellular decisions taking place on a
time scale of years to decades with the biochemical dynamics in signal
transduction and gene regulation, occuring on a time scale of minutes to hours.
We show that a stochastic bistable switch forms a viable biochemical mechanism
to implement decision processes on long time scales. As a case study, the
mechanism is applied to model the initiation of follicle growth in mammalian
ovaries, where the physiological time scale of follicle pool depletion is on
the order of the organism's lifespan. We construct a simple mathematical model
for this process based on experimental evidence for the involved genetic
mechanisms. Despite the underlying stochasticity, the proposed mechanism turns
out to yield reliable behavior in large populations of cells subject to the
considered decision process. Our model explains how the physiological time
constant may emerge from the intrinsic stochasticity of the underlying gene
regulatory network. Apart from ovarian follicles, the proposed mechanism may
also be of relevance for other physiological systems where cells take binary
decisions over a long time scale.Comment: 14 pages, 4 figure
Harnessing Naturally Occurring Tumor Immunity: A Clinical Vaccine Trial in Prostate Cancer
International audienceBACKGROUND:Studies of patients with paraneoplastic neurologic disorders (PND) have revealed that apoptotic tumor serves as a potential potent trigger for the initiation of naturally occurring tumor immunity. The purpose of this study was to assess the feasibility, safety, and immunogenicity of an apoptotic tumor-autologous dendritic cell (DC) vaccine.METHODS AND FINDINGS:We have modeled PND tumor immunity in a clinical trial in which apoptotic allogeneic prostate tumor cells were used to generate an apoptotic tumor-autologous dendritic cell vaccine. Twenty-four prostate cancer patients were immunized in a Phase I, randomized, single-blind, placebo-controlled study to assess the safety and immunogenicity of this vaccine. Vaccinations were safe and well tolerated. Importantly, we also found that the vaccine was immunogenic, inducing delayed type hypersensitivity (DTH) responses and CD4+ and CD8+ T cell proliferation, with no effect on FoxP3+ regulatory T cells. A statistically significant increase in T cell proliferation responses to prostate tumor cells in vitro (p = 0.002), decrease in prostate specific antigen (PSA) slope (p = 0.016), and a two-fold increase in PSA doubling time (p = 0.003) were identified when we compared data before and after vaccination.CONCLUSIONS:An apoptotic cancer cell vaccine modeled on naturally occurring tumor immune responses in PND patients provides a safe and immunogenic tumor vaccine
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