Statistical inference based on the nonparametric maximum likelihood estimator under double-truncation.

Fragility analysis and probabilistic performance evaluation of nuclear containment structure subjected to internal pressure

We recently proposed a representation of the bivariate survivor function as a mapping of the hazard function for truncated failure time variates. The representation led to a class of estimators that includes van der Laan's repaired nonparametric maximum likelihood estimator (NPMLE) as an important special case. We proposed a Greenwood-like variance estimator for the repaired NPMLE but found somewhat poor agreement between the empirical variance estimates and these analytic estimates for the sample sizes and bandwidths considered in our simulation study. The simulation results also confirmed those of others in showing slightly inferior performance for the repaired NPMLE compared to other competing estimators as well as a sensitivity to bandwidth choice in moderate sized samples. Despite its attractive asymptotic properties, the repaired NPMLE has drawbacks that hinder its practical application. This paper presents a modification of the repaired NPMLE that improves its performance in moderate sized samples and renders it less sensitive to the choice of bandwidth. Along with this modified estimator, more extensive simulation studies of the repaired NPMLE and Greenwood-like variance estimates are presented. The methods are then applied to a real data example.

The events of interest in any survival analysis study are regularly subject to censoring. There are various censoring schemes, including right or left censoring, and interval censoring. The most frequent censoring scheme is the right censoring, where subjects might drop out of the study or simply because not all events of interest occur before the end of the study. Moreover, for each subject, additional information referred to as covariates is registered at the beginning or throughout the study, such as age, sex, undergoing treatment, etc. The classical model to study the distribution of the events of interest, while accounting for additional information, is the Cox model. The Cox model expresses the hazard function of a subject given a set of covariates in terms of a baseline hazard, for which all covariates are zero, and an exponential function of the covariates and corresponding regression parameters. The baseline hazard can be left completely unspecified while estimating the regression parameters. Nonetheless, in practice, there are numerous studies in which the baseline hazard appears to be monotone. Time to death or to the onset of a disease are observed to have a nondecreasing baseline hazard, while the survival or recovery time after a successful medical treatment usually exhibit a nonincreasing baseline hazard. The aim of this thesis is to study the behavior of nonparametric baseline hazard and baseline density estimators in the Cox model under monotonicity constraints. The event times are assumed to be right censored and the censoring mechanism is assumed to be independent of the event of interest and non-informative. The covariates are assumed to be time-independent, usually recorded at the beginning of the study. In addition to point estimates, interval estimates of a monotone baseline hazard will be provided, based on a likelihood ratio method, along with testing at a fixed point. Furthermore, kernel smoothed estimates of a monotone baseline hazard will be defined and their behavior will be investigated. In Chapter 2, we propose several nonparametric monotone estimators of a baseline hazard or a baseline density within the Cox model. We derive the nonparametric maximum likelihood estimator of a nondecreasing baseline hazard and we consider a Grenander-type estimator, defined as the left-hand slope of the greatest convex minorant of the Breslow estimator. The two estimators are then shown to be strongly consistent and asymptotically equivalent. Moreover, we derive their common limit distribution at a fixed point. The two equivalent estimators of a nonincreasing baseline hazard and their asymptotic properties are acquired similarly. Furthermore, we introduce a Grenander-type estimator of a nonincreasing baseline density, defined as the left-hand slope of the least concave majorant of an estimator of the baseline cumulative distribution function derived from the Breslow estimator. This estimator is proven to be strongly consistent and its asymptotic distribution at a fixed point is derived. Chapter 3 provides an asymptotic linear representation of the Breslow estimator of the baseline cumulative hazard function in the Cox model. This representation can be used to derive the asymptotic distribution of the Grenander type estimator of a monotone baseline hazard estimator. The representation consists of an average of independent random variables and a term involving the difference between the maximum partial likelihood estimator and the underlying regression parameter. The order of the remainder term is arbitrarily close to n^-1. Chapter 4 focuses on interval estimation and on testing whether a monotone baseline hazard function in the Cox model has a particular value at a fixed point, via a likelihood ratio method. Nonparametric maximum likelihood estimators under the null hypothesis are defined for both nondecreasing and nonincreasing baseline hazard functions. These characterizations, along with those of the monotone nonparametric maximum likelihood estimators provide the asymptotic distribution of the likelihood ratio test. This asymptotic distribution enables, via inversion, the construction of pointwise confidence intervals. This method of constructing confidence intervals avoids the issue of estimating the nuisance parameters, as in the case of confidence intervals based on the asymptotic distribution of the estimators. Simulations indicate that the two methods yield confidence intervals with comparable coverage probabilities. Nonetheless, the confidence intervals based on the likelihood ratio are smaller, on average. Finally, in chapter 5 we consider smooth baseline hazard estimators. The estimators are obtained by kernel smoothing the maximum likelihood and Grenander-type estimators of a monotone baseline hazard function. Three different estimators are proposed for a nondecreasing baseline hazard, which are provided by the interchange of the smoothing and isotonization step. With this respect, we define a smoothed maximum likelihood estimator (SMLE), as well as a smoothed Grenander type (SG) estimator and a Grenander type smoothed (GS) estimator. All estimators are shown to be strongly pointwise or uniformly consistent.

The nonparametric maximum likelihood estimation (NPMLE) of the distribution function from the interval censored (IC) data has been extensively studied in the extant literature. The NPMLE was also developed for the subdistribution functions in an IC competing risks model and in an illness-death model under various interval-censoring scenarios. But the important problem of estimation of the cumulative intensities (CIs) in the interval-censored models has not been considered previously. We develop the NPMLE of the CI in a simple alive/dead model and of the CIs in a competing risks model. Assuming that data are generated by a discrete and finite mixed case interval censoring mechanism we provide a discussion and the simulation study of the asymptotic properties of the NPMLEs of the CIs. In particular we show that they are asymptotically unbiased; in contrast the ad hoc estimators presented in extant literature are substantially biased. We illustrate our methods with the data from a prospective cohort study on the longevity of dental veneers.

We show that under reasonable conditions the nonparametric maximum likelihood estimate (NPMLE) of the distribution function from left-truncated and case 1 interval-censored data is inconsistent, in contrast to the consistency properties of the NPMLE from only left-truncated data or only interval-censored data. However, the conditional NPMLE is shown to be consistent. Numerical examples are provided to illustrate their finite sample properties.

A receiver operating characteristic (ROC) curve plots the true positive rate of a classier against its false positive rate, both of which are accuracy measures of the classier. The ROC curve has several interesting geometrical properties, including concavity which is a neces- sary condition for a classier to be optimal. In this paper, we study the nonparametric maximum likelihood estimator (NPMLE) of a con- cave ROC curve and its modication to reduce bias. We characterize the NPMLE as a solution to a geometric programming, a special type of a mathematical optimization problem. Wend that the NPMLE is close to the convex hull of the empirical ROC curve and, thus, has smaller variance but positive bias at a given false positive rate. To reduce the bias, we propose a modication of the NPMLE which minimizes the L1 distance from the empirical ROC curve. We numerically compare the �nite sample performance of three estimators, the empirical ROC curve, the NMPLE, and the modied NPMLE. Finally, we apply the estimators to estimating the optimal ROC curve of the variance-thresho classier to segment a low depth ofeld image and tonding a diagnostic tool with multiple tests for detection of hemophilia A carrier.

We study efficient nonparametric estimation of distribution functions of several scientifically meaningful sub-populations from data consisting of mixed samples where the sub-population identifiers are missing. Only probabilities of each observation belonging to a sub-population are available. The problem arises from several biomedical studies such as quantitative trait locus (QTL) analysis and genetic studies with ungenotyped relatives where the scientific interest lies in estimating the cumulative distribution function of a trait given a specific genotype. However, in these studies subjects' genotypes may not be directly observed. The distribution of the trait outcome is therefore a mixture of several genotype-specific distributions. We characterize the complete class of consistent estimators which includes members such as one type of nonparametric maximum likelihood estimator (NPMLE) and least squares or weighted least squares estimators. We identify the efficient estimator in the class that reaches the semiparametric efficiency bound, and we implement it using a simple procedure that remains consistent even if several components of the estimator are mis-specified. In addition, our close inspections on two commonly used NPMLEs in these problems show the surprising results that the NPMLE in one form is highly inefficient, while in the other form is inconsistent. We provide simulation procedures to illustrate the theoretical results and demonstrate the proposed methods through two real data examples.

Multivariate, heteroscedastic errors complicate statistical inference in many large-scale denoizing problems. Empirical Bayes is attractive in such settings, but standard parametric approaches rest on assumptions about the form of the prior distribution which can be hard to justify and which introduce unnecessary tuning parameters. We extend the nonparametric maximum-likelihood estimator (NPMLE) for Gaussian location mixture densities to allow for multivariate, heteroscedastic errors. NPMLEs estimate an arbitrary prior by solving an infinite-dimensional, convex optimization problem; we show that this convex optimization problem can be tractably approximated by a finite-dimensional version. The empirical Bayes posterior means based on an NPMLE have low regret, meaning they closely target the oracle posterior means one would compute with the true prior in hand. We prove an oracle inequality implying that the empirical Bayes estimator performs at nearly the optimal level (up to logarithmic factors) for denoizing without prior knowledge. We provide finite-sample bounds on the average Hellinger accuracy of an NPMLE for estimating the marginal densities of the observations. We also demonstrate the adaptive and nearly optimal properties of NPMLEs for deconvolution. We apply our method to two denoizing problems in astronomy and to two hierarchical linear modelling problems in social science and biology.

We develop the non-parametric maximum likelihood estimator (MLE) of the full Mbh capture-recapture model which utilizes both initial capture and recapture data and permits both heterogeneity (h) between animals and behavioural (b) response to capture. Our MLE procedure utilizes non-parametric maximum likelihood estimation of mixture distributions (Lindsay, 1983; Lindsay and Roeder, 1992) and the EM algorithm (Dempsteret al., 1977). Our MLE estimate provides the first non-parametric estimate of the bivariate capture-recapture distribution. Since non-parametric maximum likelihood estimation exists for submodels Mh (allowing heterogeneity only), Mb (allowing behavioural response only) and M0 (allowing no changes), we develop maximum likelihood-based model selection, specifically the Akaike information criterion (AIC) (Akaike, 1973). The AIC procedure does well in detecting behavioural response but has difficulty in detecting heterogeneity.

Bootstrap is a returned re-sampling method used to estimate the variance component and their variability. Adjusted bootstrap method was used by Wiley in p×i design for normal data in 2001. However, Wiley did not compare the difference between adjusted method and unadjusted method when estimating the variability. To expand Wiley’s 2001 study, our study applied Monte Carlo method to simulate four distribution data. The aim of simulation is to explore the effects of four different estimation methods when estimating the variability of estimated variance components for generalizability theory. The four distribution data are normal distribution data, dichotomous distribution data, polytomous distribution data and skewed distribution data. It is common that researchers focus on normal distribution data and neglect non-normal distribution data, yet non-normal distribution data could always be seen in tests such as TOEFL and GRE. There are several methods to estimate the variability of variance components, including traditional, bootstrap, jackknife and Markov Chain Monte Carlo (MCMC). Former research by Li and Zhang (2009) shows that bootstrap method is significantlybetter than traditional, jackknife, and MCMC methods in estimating the variability for four distribution data. Bootstrap method has superior cross-distribution quality when estimating the variability of estimated variance components. Li and Zhang (2009) also suggest that bootstrap method should be adopted with a divide-and-conquer strategy to obtain good estimated standard error and estimated confidence interval and the criteria of such strategy should be set to: boot-p for person, boot-pi for item, and boot-i for person and item. However, it is unclear that which of the bootstrap methods (adjusted and unadjusted) is better for boot-p, boot-pi, and boot-i. Therefore, our study intends to probe into this comparison as well. This aim of the study is to explore whether adjusted bootstrap method is superior to unadjusted method in improving the estimation of variance components and their variability relative for generalizability theory. The simulation is implemented in R statistical programming environment. To simulate skewed data, HyperbolicDist package is used. Some criteria are set to compare the four methods. The bias is considered when variance components and their standard errors are estimated. The smaller the absolute bias is, the more reliable the result is. The criterion of confidence intervals is 80% interval coverage. If the 80% interval coverage is closer to 0.80, the confidence interval is more reliable. The results indicate that for four distribution data, adjusted bootstrap method is superior to unadjusted bootstrap method whether in point estimation of variance components or in variability estimation of variance components. For its improvement of the estimation of variance components and their variability for generalizability theory, adjusted bootstrap should be adopted as soon as possible.

Causal mediation modeling has become a popular approach for studying the effect of an exposure on an outcome through mediators. Currently, the literature on mediation analyses with survival outcomes largely focused on settings with a single mediator and quantified the mediation effects on the hazard, log hazard and log survival time (Lange and Hansen 2011; VanderWeele 2011). In this article, we propose a multi-mediator model for survival data by employing a flexible semiparametric probit model. We characterize path-specific effects (PSEs) of the exposure on the outcome mediated through specific mediators. We derive closed form expressions for PSEs on a transformed survival time and the survival probabilities. Statistical inference on the PSEs is developed using a nonparametric maximum likelihood estimator under the semiparametric probit model and the functional Delta method. Results from simulation studies suggest that our proposed methods perform well in finite sample. We illustrate the utility of our method in a genomic study of glioblastoma multiforme survival.

A confidence interval is an interval estimate of a parameter of a population calculated from a sample drawn from the population. Bootstrapping method, which involves producing several new data sets that are resampled from the original data in order to estimate parameter for each newly created data set, allowing an empirical distribution for the parameter to be estimated. Since certain statistics are harder to estimate, confidence intervals are rarely employed. Several statistics might necessitate multi-step formulas assuming that are impractical for calculating confidence intervals. This paper reviews research on the concept of bootstrapping and bootstrap confidence interval. The current narrative analysis was developed to answer the main research question: (1) What is the concept of the bootstrap method and bootstrap confidence interval? (2) What are the methods of bootstrapping to obtain confidence interval? This study has found general bootstrap method idea, various techniques of bootstrap methods, its advantages and disadvantages, and its limitations. There are normal interval method, percentile bootstrap method, basic method, first-order normal approximation method, bias-corrected bootstrap, accelerated bias-corrected bootstrap and bootstrap-t method. This study concludes that the advantages of using bootstrap CI is that it does not require any assumptions about the shape of distribution and universality of the approach. Bootstrapping is a computer-intensive statistical technique that relies significantly on modern high-speed digital computers to do massive computations.

SUMMARY A great deal of recent attention has focused on the estimation of survival distributions based on current status data, an extreme form of interval censored data. This particular data structure arises in a wide variety of applications where cross-sectional observation either naturally occurs or is preferred to more traditional forms of follow-up. Here we consider current status data in the context of competing risks. We briefly consider simple parametric models as a backdrop to nonparametric procedures. We make some brief comparisons and remarks regarding the nonparametric maximum likelihood estimator. The ideas are illustrated on the data of Krailo & Pike (1983) which considers estimation of the age distribution at both natural and operative menopause. We also consider the case where there is exact observation of failure times due to one of the competing risks when failure occurs prior to the monitoring time. Basic techniques of survival analysis focus on estimation of the survival distribution based on various forms of censored data. An extreme form of censoring arises where the only information on studied individuals is their survival status at a single monitoring time. This particular data structure is known as current status data. Nonparametric estimation of the survival function and semiparametric techniques for related regression models, based on current status data, have been much studied of late. Here, we consider estimation of sub-survival functions based on current status observations in the presence of competing risks. For simplicity, we describe only two competing risks, but the ideas are easily extended when there are more than two possible causes of failure. Let )j denote the cause-specific hazard function for cause j = 1, 2 (Kalbfleisch & Prentice, 2002, p. 252). If T and J are the random variables that measure time to failure and cause of failure, respectively, the two sub-distribution functions of interest are

Measurement uncertainty for < 905 > Uniformity of Dosage Units tests using Monte Carlo and bootstrapping methods – Uncertainties arising from sampling and analytical steps

ObjectiveThe purpose of this study is to compare the performance of the four estimation methods (traditional method, jackknife method, bootstrap method, and MCMC method), find the optimal one, and make a set of unified rules for Bootstrap.MethodsBased on four types of simulated data (normal, dichotomous, polytomous, and skewed data), this study estimates and compares the estimated variance components and their variability of the four estimation methods when using a p×i design in generalizability theory. The estimated variance components are vc.p, vc.i and vc.pi and the variability of estimated variance components are their estimated standard errors (SE(vc.p), SE(vc.i) and SE(vc.pi)) and confidence intervals (CI(vc.p), CI(vc.i) and CI(vc.pi)).ResultsFor the normal data, all the four methods can accurately estimate the variance components and their variability. For the dichotomous data, the |RPB| of SE (vc.i) of traditional method is 128.5714, the |RPB| of SE (vc.i), SE (vc.pi) and CI (vc.i) of jackknife method are 42.8571, 43.6893 and 40.5000, which are larger than 25 and not accurate. For the polytomous data, the |RPB| of SE (vc.i) and CI (vc.i) of MCMC method are 59.6612 and 45.2500, which are larger than 25 and not accurate. For the skewed data, the |RPB| of SE (vc.p), SE (vc.i) and SE (vc. pi) of traditional method and MCMC method are over 25, which are not accurate. Only the bootstrap method can estimate variance components and their variability accurately across different data distribution. Nonetheless, the divide-and-conquer strategy must be used when adopting the bootstrap method.ConclusionsThe bootstrap method is optimal among the four methods and shows the cross-distribution superiority over the other three methods. However, a set of unified rules for the divide-and-conquer strategy need to be recommended for the bootstrap method, which is optimal when boot-p for p (person), boot-pi for i (item), and boot-i for pi (person × item).