An Efficient Stochastic Approximation Algorithm and Model Selection for a Class of Nonlinear Random Effect Models with Incomplete Responses

The EM algorithm is a widely used technique for finding maximum likelihood (ML) estimates when the data are not fully observed. Despite its popularity for computing ML estimates in unrestricted problems and the need for simplified computations for problems with equality and inequality restrictions, there have been few applications of the algorithm to restricted ML estimation. The EM algorithm is presented for restricted ML estimation and provides its applications to the probit model under equality and inequality restrictions using two small data sets.

Local influence analysis of nonlinear structural equation models with nonignorable missing outcomes from reproductive dispersion models

The pharmaceutical industry is currently interested in the population approach and population models, also known as mixed effects models and random effects models depending on the precise form. Population models are useful in that they can account for both withinand between-individual sources of variability and serial correlation within individual observations when analyzing unbalanced repeated measures data. The modelling of population pharmacodynamic or pharmacokinetic profiles typically involves nonlinear random effects models. Each individual's observations are modelled by identical (up to unknown parameter values) nonlinear regression models, with the distribution of the observations, or a transformation of the observations, about expected responses taken to be normal, with the degree of variability described by a variance model. Between-individual variability is modelled by a population distribution for the individual regression parameter values (random effects). In a parametric analysis the population distribution is taken to be normal, the parameters of which, along with the parameters of the variance model, are known as the population parameters. Maximum likelihood estimation of the population parameters for nonlinear random effects models was pioneered by Beal and Sheiner (1979), and since then a number of algorithms have appeared for approximate maximum likelihood, including Steimer et al. (1984), Lindstrom and Bates (1990), Beal and Sheiner (1992), and Mentre and Gomeni (1995). All of these algorithms are approximate in some way. For a summary see Beal and Sheiner (1992), Wolfinger (1993), Pinheiro and Bates (1994), and Davidian and Giltinan (1995). In this paper an EM algorithm for exact maximum likelihood estimation is introduced. An EM algorithm obtaining maximum likelihood estimates for linear random effects models was introduced by Dempster, Laird, and Rubin (1977). Laird and Ware (1982), Lindstrom and Bates (1988), Jennrich and Schluchter (1986), and Liu and Rubin (1994) all describe hybrid EM algorithms for the linear random effects model. A true EM algorithm for the linear model is described by Jamshidian and Jennrich (1993). Mentre and Gomeni (1995) describe an approximate EM algorithm for nonlinear random effects models and, from the algorithm given in this paper, it can be seen clearly how their approximations arise. The present algorithm uses Monte Carlo methods to perform the E step, a strategy previously adopted in an altogether different model by Guo and Thompson (1994). Guo and Thompson require a Gibbs sampler, that is, a Markov chain Monte Carlo method for their E step, but the present algorithm uses independent samples. In Section 2 of this paper the nonlinear random effects model is described. Section 3 gives the EM algorithm without random effect covariates, while Section 4 gives the modified algorithm in the

Finite mixtures of multivariate skew t (MST) distributions have proven to be useful in modelling heterogeneous data with asymmetric and heavy tail behaviour. Recently, they have been exploited as an effective tool for modelling flow cytometric data. A number of algorithms for the computation of the maximum likelihood (ML) estimates for the model parameters of mixtures of MST distributions have been put forward in recent years. These implementations use various characterizations of the MST distribution, which are similar but not identical. While exact implementation of the expectation-maximization (EM) algorithm can be achieved for `restricted' characterizations of the component skew t-distributions, Monte Carlo (MC) methods have been used to fit the `unrestricted' models. In this paper, we review several recent fitting algorithms for finite mixtures of multivariate skew t-distributions, at the same time clarifying some of the connections between the various existing proposals. In particular, recent results have shown that the EM algorithm can be implemented exactly for faster computation of ML estimates for mixtures with unrestricted MST components. The gain in computational time is effected by noting that the semi-infinite integrals on the E-step of the EM algorithm can be put in the form of moments of the truncated multivariate non-central t-distribution, similar to the restricted case, which subsequently can be expressed in terms of the non-truncated form of the central t-distribution function for which fast algorithms are available. We present comparisons to illustrate the relative performance of the restricted and unrestricted models, and demonstrate the usefulness of the recently proposed methodology for the unrestricted MST mixture, by some applications to three real datasets.

In order to have confidence in model-based phylogenetic analysis, the model of nucleotide substitution adopted must be selected in a statistically rigorous manner. Several model-selection methods are applicable to maximum likelihood (ML) analysis, including the hierarchical likelihood-ratio test (hLRT), Akaike information criterion (AIC), Bayesian information criterion (BIC), and decision theory (DT), but their performance relative to empirical data has not been investigated thoroughly. In this study, we use 250 phylogenetic data sets obtained from TreeBASE to examine the effects that choice in model selection has on ML estimation of phylogeny, with an emphasis on optimal topology, bootstrap support, and hypothesis testing. We show that the use of different methods leads to the selection of two or more models for approximately 80% of the data sets and that the AIC typically selects more complex models than alternative approaches. Although ML estimation with different best-fit models results in incongruent tree topologies approximately 50% of the time, these differences are primarily attributable to alternative resolutions of poorly supported nodes. Furthermore, topologies and bootstrap values estimated with ML using alternative statistically supported models are more similar to each other than to topologies and bootstrap values estimated with ML under the Kimura two-parameter (K2P) model or maximum parsimony (MP). In addition, Swofford-Olsen-Waddell-Hillis (SOWH) tests indicate that ML trees estimated with alternative best-fit models are usually not significantly different from each other when evaluated with the same model. However, ML trees estimated with statistically supported models are often significantly suboptimal to ML trees made with the K2P model when both are evaluated with K2P, indicating that not all models perform in an equivalent manner. Nevertheless, the use of alternative statistically supported models generally does not affect tests of monophyletic relationships under either the Shimodaira-Hasegawa (S-H) or SOWH methods. Our results suggest that although choice in model selection has a strong impact on optimal tree topology, it rarely affects evolutionary inferences drawn from the data because differences are mainly confined to poorly supported nodes. Moreover, since ML with alternative best-fit models tends to produce more similar estimates of phylogeny than ML under the K2P model or MP, the use of any statistically based model-selection method is vastly preferable to forgoing the model-selection process altogether.

Many diseases show dichotomous phenotypic variation but do not follow a simple Mendelian pattern of inheritance. Variances of these binary diseases are presumably controlled by multiple loci and environmental variants. A least-squares method has been developed for mapping such complex disease loci by treating the binary phenotypes (0 and 1) as if they were continuous. However, the least-squares method is not recommended because of its ad hoc nature. Maximum Likelihood (ML) and Bayesian methods have also been developed for binary disease mapping by incorporating the discrete nature of the phenotypic distribution. In the ML analysis, the likelihood function is usually maximized using some complicated maximization algorithms (e.g. the Newton-Raphson or the simplex algorithm). Under the threshold model of binary disease, we develop an Expectation Maximization (EM) algorithm to solve for the maximum likelihood estimates (MLEs). The new EM algorithm is developed by treating both the unobserved genotype and the disease liability as missing values. As a result, the EM iteration equations have the same form as the normal equation system in linear regression. The EM algorithm is further modified to take into account sexual dimorphism in the linkage maps. Applying the EM-implemented ML method to a four-way-cross mouse family, we detected two regions on the fourth chromosome that have evidence of QTLs controlling the segregation of fibrosarcoma, a form of connective tissue cancer. The two QTLs explain 50-60% of the variance in the disease liability. We also applied a Bayesian method previously developed (modified to take into account sex-specific maps) to this data set and detected one additional QTL on chromosome 13 that explains another 26% of the variance of the disease liability. All the QTLs detected primarily show dominance effects.

The Maximum Likelihood (ML) and Best Linear Unbiased (BLU) estimators of the location and scale parameters of an extreme value distribution (Lawless [1982]) are compared under conditions of small sample sizes and Type I censorship. The comparisons were made in terms of the mean square error criterion. According to this criterion, the ML estimator of σ in the case of very small sample sizes (n < 10) and heavy censorship (low censoring time) proved to be more efficient than the corresponding BLU estimator. However, the BLU estimator for σ attains parity with the corresponding ML estimator when the censoring time increases even for sample sizes as low as 10. The BLU estimator of σ attains equivalence with the ML estimator when the sample size increases above 10, particularly when the censoring time is also increased. The situation is reversed when it came to estimating the location parameter μ, as the BLU estimator was found to be consistently more efficient than the ML estimator despite the improved performance of the ML estimator when the sample size increases. However, computational ease and convenience favor the ML estimators. Keywords: maximum likelihood estimatorsbest linear unbiased estimatorslife-testingreliability

MCOIN: a novel heuristic for determining TFBS motif width

Multiple imputation and maximum likelihood estimation (via the expectation‐maximization algorithm) are two well‐known methods readily used for analyzing data with missing values. While these two methods are often considered as being distinct from one another, multiple imputation (when using improper imputation) is actually equivalent to a stochastic expectation‐maximization approximation to the likelihood. In this article, we exploit this key result to show that familiar likelihood‐based approaches to model selection, such as Akaike's information criterion (AIC) and the Bayesian information criterion (BIC), can be used to choose the imputation model that best fits the observed data. Poor choice of imputation model is known to bias inference, and while sensitivity analysis has often been used to explore the implications of different imputation models, we show that the data can be used to choose an appropriate imputation model via conventional model selection tools. We show that BIC can be consistent for selecting the correct imputation model in the presence of missing data. We verify these results empirically through simulation studies, and demonstrate their practicality on two classical missing data examples. An interesting result we saw in simulations was that not only can parameter estimates be biased by misspecifying the imputation model, but also by overfitting the imputation model. This emphasizes the importance of using model selection not just to choose the appropriate type of imputation model, but also to decide on the appropriate level of imputation model complexity.

In this paper, a computationally efficient algorithm is presented for joint maximum likelihood (ML) timing and carrier phase estimation of OFDM systems employing M-PSK modulation scheme with additive Gaussian noise, based on the expectation-maximization (EM) algorithm. A nondata-aided (NDA) scheme is considered for the joint timing and phase synchronizer which maximizes the low SNR limit of the likelihood function averaged over the M-PSK signal constellation. For this, an EM algorithm is derived which estimates the timing offset and the phase rotations of each subcarrier iteratively and which converges to the true ML estimation of the unknown timing and phase. It is shown that the algorithm becomes independent of the signal-to-noise ratio for both low and high SNR cases. The algorithm is applied to the QPSK modulated OFDM systems and it is concluded that for SNR values greater than 10 dB the convergence is achieved in first iteration and for SNR values less than 10 dB, at most in three iterations. It is also concluded that the convergence is independent of the initial starting points.

The Multiple Comparison Procedures with Modeling Techniques (MCP-Mod) framework has been recently approved by the U.S. Food, Administration, and European Medicines Agency as fit-for-purpose for phase II studies. Nonetheless, this approach relies on the asymptotic properties of Maximum Likelihood (ML) estimators, which might not be reasonable for small sample sizes. In this paper, we derived improved ML estimators and correction for their covariance matrices in the censored Weibull regression model based on the corrective and preventive approaches. We performed two simulation studies to evaluate ML and improved ML estimators with their covariance matrices in (i) a regression framework (ii) the Multiple Comparison Procedures with Modeling Techniques framework. We have shown that improved ML estimators are less biased than ML estimators yielding Wald-type statistics that controls type I error without loss of power in both frameworks. Therefore, we recommend the use of improved ML estimators in the MCP-Mod approach to control type I error at nominal value for sample sizes ranging from 5 to 25 subjects per dose.

For a balanced two‐way mixed model, the maximum likelihood (ML) and restricted ML (REML) estimators of the variance components were obtained and compared under the non‐negativity requirements of the variance components by Lee and Kapadia (1984). In this note, for a mixed (random blocks) incomplete block model, explicit forms for the REML estimators of variance components are obtained. They are always non‐negative and have smaller mean squared error (MSE) than the analysis of variance (AOV) estimators. The asymptotic sampling variances of the maximum likelihood (ML) estimators and the REML estimators are compared and the balanced incomplete block design (BIBD) is considered as a special case. The ML estimators are shown to have smaller asymptotic variances than the REML estimators, but a numerical result in the randomized complete block design (RCBD) demonstrated that the performances of the REML and ML estimators are not much different in the MSE sense.

Over-the-air computation (OAC) is a promising technique to realize fast model aggregation in the uplink of federated edge learning (FEEL). OAC, however, hinges on accurate channel-gain precoding and strict synchronization among edge devices, which are challenging in practice. As such, how to design the maximum likelihood (ML) estimator in the presence of residual channel-gain mismatch and asynchronies is an open problem. To fill this gap, this paper formulates the problem of misaligned OAC for FEEL and puts forth a whitened matched filtering and sampling scheme to obtain oversampled, but independent samples from the misaligned and overlapped signals. Given the whitened samples, a sum-product ML (SP-ML) estimator and an aligned-sample estimator are devised to estimate the arithmetic sum of the transmitted symbols. In particular, the computational complexity of our SP-ML estimator is linear in the packet length, and hence is significantly lower than the conventional ML estimator. Extensive simulations on the test accuracy versus the average received energy per symbol to noise power spectral density ratio (EsN0) yield two main results: 1) In the low EsN0 regime, the aligned-sample estimator can achieve superior test accuracy provided that the phase misalignment is not severe. In contrast, the ML estimator does not work well due to the error propagation and noise enhancement in the estimation process. 2) In the high EsN0 regime, the ML estimator attains the optimal learning performance regardless of the severity of phase misalignment. On the other hand, the aligned-sample estimator suffers from a test-accuracy loss caused by phase misalignment.

A maximum likelihood (ML) estimator is developed for determining time delay between signals received at two spatially separated sensors in the presence of uncorrelated noise. This ML estimator can be realized as a pair of receiver prefilters followed by a cross correlator. The time argument at which the correlator achieves a maximum is the delay estimate. The ML estimator is compared with several other proposed processors of similar form. Under certain conditions the ML estimator is shown to be identical to one proposed by Hannan and Thomson [10] and MacDonald and Schultheiss [21]. Qualitatively, the role of the prefilters is to accentuate the signal passed to the correlator at frequencies for which the signal-to-noise (S/N) ratio is highest and, simultaneously, to suppress the noise power. The same type of prefiltering is provided by the generalized Eckart filter, which maximizes the S/N ratio of the correlator output. For low S/N ratio, the ML estimator is shown to be equivalent to Eckart prefiltering.

The reverberation power spectral density (PSD) is often required for dereverberation and noise reduction algorithms. In this work, we compare two maximum likelihood (ML) estimators of the reverberation PSD in a noisy environment. In the first estimator, the direct path is first blocked. Then, the ML criterion for estimating the reverberation PSD is stated according to the probability density function of the blocking matrix (BM) outputs. In the second estimator, the speech component is not blocked. Instead, the ML criterion for estimating the speech and reverberation PSD is stated according to the probability density function of the microphone signals. To compare the expected mean square error (MSE) between the two ML estimators of the reverberation PSD, the Cramer–Rao Bounds (CRBs) for the two ML estimators are derived. We show that the CRB for the joint reverberation and speech PSD estimator is lower than the CRB for estimating the reverberation PSD from the BM outputs. Experimental results show that the MSE of the two estimators indeed obeys the CRB curves. Experimental results of multimicrophone dereverberation and noise reduction algorithm show the benefits of using the ML estimators in comparison with another baseline estimators.