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Innovations in bayes and empirical bayes methods: estimating parameters, populations and ranks.

By formalizing the relation among components and 'borrowing information' among them, Bayes and empirical Bayes methods can produce more valid, efficient and informative statistical evaluations than those based on traditional methods. In addition, Bayesian structuring of complicated models and goals guides development of appropriate statistical approaches and generates summaries which properly account for sampling and modelling uncertainty. Computing innovations enable implementation of complex and relevant models, thereby substantially increasing the role of Bayes/empirical Bayes methods in important statistical assessments. Policy-relevant statistical assessments involve synthesis of information from a set of related components such as medical clinics, geographic regions or research studies. Typical assessments include inference for individual parameters, synthesis over the collection of components (for example, the parameter histogram) and comparisons among parameters (for example, ranks). The relative importance of these goals depends on the context. Bayesian structuring provides a guide to valid inference. For example, while posterior means are the 'obvious' and optimal estimates for individual components under squared error loss, their empirical distribution function (EDF) is underdispersed and never valid for estimating the EDF of the true, underlying parameters. Effective histogram estimates result from optimizing a loss function based in a distance between the histogram and its estimate. Similarly, ranking observed data usually produces poor estimates and ranking posterior means can be inappropriate. Effective estimates should be based on a loss function that caters directly to ranks. Using examples of 'borrowing information', shrinkage and the variance/bias trade-off we motivate Bayes and empirical Bayes analysis. Then, we outline the formal approach and discuss 'triple-goal' estimates with values that when ranked produce optimal ranks, for which the EDF is an optimal estimate of the parameter EDF and such that the values themselves are effective estimates of co-ordinate-specific parameters. We use basic models and data analysis examples to highlight the conceptual and structural issues.

Animals↗

Non-parametric analysis of transfusion-related HIV and AIDS incidence data.

The method for making non-parametric inferences about the probability distribution of the incubation period for AIDS from transfusion-related AIDS data is extended to include data on individuals who have tested positive for HIV but do not have AIDS at the time of analysis. The method is illustrated with data on individuals infected by transfusion in Australia. The shape of the incubation distribution, as represented by the truncated distribution function, can be estimated, but the additional data contribute very little to the estimation of this shape. With a general non-parametric form for the incubation distribution the additional data do not overcome the identifiability problem that exists for non-parametric estimation of this distribution from AIDS data alone. If quarterly rates for HIV testing are specified, the additional data make it possible to estimate the cumulative distribution function for the incubation period. This is also possible when a simple parametric form, with one or two unknown parameters, is used for the testing rates. However, the additional data do not allow effective estimation of the HIV testing rates. The estimated shape of the incubation distribution indicates a higher proportion of short incubation periods than an earlier estimate based on U.S. data. Estimates for the incubation distribution itself do not vary much over a plausible range of HIV testing rates.

Acquired Immunodeficiency Syndrome↗

Soft and hard classification by reproducing kernel Hilbert space methods.

Reproducing kernel Hilbert space (RKHS) methods provide a unified context for solving a wide variety of statistical modelling and function estimation problems. We consider two such problems: We are given a training set [yi, ti, i = 1, em leader, n], where yi is the response for the ith subject, and ti is a vector of attributes for this subject. The value of y(i) is a label that indicates which category it came from. For the first problem, we wish to build a model from the training set that assigns to each t in an attribute domain of interest an estimate of the probability pj(t) that a (future) subject with attribute vector t is in category j. The second problem is in some sense less ambitious; it is to build a model that assigns to each t a label, which classifies a future subject with that t into one of the categories or possibly "none of the above." The approach to the first of these two problems discussed here is a special case of what is known as penalized likelihood estimation. The approach to the second problem is known as the support vector machine. We also note some alternate but closely related approaches to the second problem. These approaches are all obtained as solutions to optimization problems in RKHS. Many other problems, in particular the solution of ill-posed inverse problems, can be obtained as solutions to optimization problems in RKHS and are mentioned in passing. We caution the reader that although a large literature exists in all of these topics, in this inaugural article we are selectively highlighting work of the author, former students, and other collaborators.

Classification↗

The variance reaction time model.

The variance reaction time model (VRTM) is proposed to account for various recognition data on reaction time, the mirror effect, receiver-operating-characteristic (ROC) curves, etc. The model is based on simple and plausible assumptions within a neural network: VRTM is a two layer neural network where one layer represents items and one layer represents contexts. The recognition decision is based on a random walk of nodes activated at recognition. VRTM suggests theoretical constraints on the distributions of nodes activated at recognition and the noise in the random walk. The variability in the net inputs to nodes depends on the item frequency (the number of times that the item has been encoded) and the list length. The essential mechanism that accounts for the empirical data is a non-linear activation function. The mean activation threshold in the non-linear activation function is placed to achieve efficient discriminability between new and old items and there is variability in the activation threshold. VRTM predicts the mirror effect for low and high frequency words, a strength based mirror effect between conditions but not within one condition, appropriate ROC-curves for old/new and high/low frequency items, and list-length effects. Furthermore, it predicts appropriate means and distributions of reaction times for old/new, correct/incorrect, and high/low frequency items as well as speed/accuracy tradeoffs. VRTM has an explicit mathematical solution, it is simulated in a neural network, and it is fitted to a number of datasets.

Attention↗

Parametric modeling of reaction time experiment data.

A simple parametric model is proposed for data from a point-process version of a reaction time experiment. It is used to statistically check for the presence and nature of nonlinear inhibition in the eye-brain-hand system, as well as to study the nature of the reaction time delay distribution. The model tells us that, in principle, the second-order intensity estimate can be used to determine whether the experimental subject is systematically observing the first or the second of two flashes transmitted in short succession. Nonparametric estimates of second-order intensity functions are used in conjunction with this model. In particular, the model allows for the computation of good bandwidths for intensity curve estimation. A parametric bootstrap can also be implemented. Our methods are illustrated with 12 runs of data from a real reaction time experiment. It is found that nonlinear inhibition is present in the eye-brain-hand system. However, there are insufficient data to distinguish between log-normality and normality in the reaction time distribution, due partly to confounding with the particular kind of nonlinear inhibition present in the system.

Biometry↗

The effect of crown length on the fracture resistance of posterior porcelain and glass-ceramic crowns.

This in vitro study measured the changes in the fracture resistance of posterior crowns as a function of crown length. The crowns, 10 for each group, were made of a feldspathic porcelain (Ceramco), a glass-ceramic material (Dicor), and an alumina-reinforced glass (In-Ceram). Three different crown lengths were tested on acrylic resin dies. The restorations were fractured in a testing machine using a steel ball, 12.7 mm in diameter, that contacted the occlusal surface at three distinct points. Statistical analysis was performed using the Weibull distribution. The fracture resistance increased significantly with increasing crown length for all crown materials.

Aluminum Oxide↗

Estimation of the depth-dependent component of the point spread function of SPECT.

The point spread function (PSF) of a gamma camera describes the photon count density distribution at the detector surface when a point source is imaged. Knowledge of the PSF is important for computer simulation and accurate image reconstruction of single photon emission computed tomography (SPECT) images. To reduce the number of measurements required for PSF characterization and the amount of computer memory to store PSF tables, and to enable generalization of the PSF to different collimator-to-source distances, the PSF may be modeled as the two-dimensional (2D) convolution of the depth-dependent component which is free of detector blurring (PSF(ideal)) and the distance-dependent detector response. Owing to limitations imposed by the radioactive strength of point sources, extended sources have to be used for measurements. Therefore, if PSF(ideal) is estimated from measured responses, corrections have to be made for both the detector blurring and for the extent of the source. In this paper, an approach based on maximum likelihood expectation-maximization (ML-EM) is used to estimate PSF(ideal). In addition, a practical measurement procedure which avoids problems associated with commonly used line-source measurements is proposed. To decrease noise and to prevent nonphysical solutions, shape constraints are applied during the estimation of PSF(ideal). The estimates are generalized to depths other than those which have been measured and are incorporated in a SPECT simulator. The method is validated for Tc-99m and T1-201 by means of measurements on physical phantoms. The corrected responses have the desired shapes and simulated responses closely resemble measured responses. The proposed methodology may, consequently, serve as a basis for accurate three-dimensional (3D) SPECT reconstruction.

Algorithms↗

Multiple site electromyograph amplitude estimation.

Temporal whitening of individual surface electromyograph (EMG) waveforms and spatial combination of multiple recording sites have separately been demonstrated to improve the performance of EMG amplitude estimation. This investigation combined these two techniques by first whitening, then combining the data from multiple EMG recording sites to form an EMG amplitude estimate. A phenomenological mathematical model of multiple sites of the surface EMG waveform, with analytic solution for an optimal amplitude estimate, is presented. Experimental surface EMG waveforms were then sampled from multiple sites during nonfatiguing, constant-force, isometric contractions of the biceps or triceps muscles, over the range of 10-75% maximum voluntary contraction. A signal-to-noise ratio (SNR) was computed from each amplitude estimate (deviations about the mean value of the estimate were considered as noise). Results showed that SNR performance: 1) increased with the number of EMG sites, 2) was a function of the sampling frequency, 3) was predominantly invariant to various methods of determining spatial uncorrelation filters, 4) was not sensitive to the intersite correlations of the electrode configuration investigated, and 5) was best at lower levels of contraction. A moving average root mean square estimator (245-ms window) provided an average +/- standard deviation (A +/- SD) SNR of 10.7 +/- 3.3 for single site unwhitened recordings. Temporal whitening and four combined sites improved the A +/- SD SNR to 24.6 +/- 10.4. On one subject, eight whitened combined sites were achieved, providing an A +/- SD SNR or 35.0 +/- 13.4.

Adult↗

A hybrid Bayesian adaptive design for dose response trials.

In recent years, the use of adaptive design methods based on accrued data of on-going trials have become very popular for dose response trials in early clinical development due to their flexibility (EMEA, 2002). In this paper, we developed a hybrid frequentist-Bayesian continual reassessment method (CRM) in conjunction with utility-adaptive randomization for clinical trial designs with multiple endpoints. The proposed hyperlogistic function family with multiple parameters gives users flexibility for probability modeling. CRM reassesses a dose-response relationship based on accrued data of the on-going trial, which allows investigators to make decisions based on a constantly updated dose-response model. The proposed utility-adaptive randomization for multiple-endpoint trials allows more patients to be assigned to superior treatment groups. The performance of the proposed method was examined in terms of its operating characteristics through computer simulations.

Algorithms↗

Accuracy of haplotype frequency estimation for biallelic loci, via the expectation-maximization algorithm for unphased diploid genotype data.

Haplotype analyses have become increasingly common in genetic studies of human disease because of their ability to identify unique chromosomal segments likely to harbor disease-predisposing genes. The study of haplotypes is also used to investigate many population processes, such as migration and immigration rates, linkage-disequilibrium strength, and the relatedness of populations. Unfortunately, many haplotype-analysis methods require phase information that can be difficult to obtain from samples of nonhaploid species. There are, however, strategies for estimating haplotype frequencies from unphased diploid genotype data collected on a sample of individuals that make use of the expectation-maximization (EM) algorithm to overcome the missing phase information. The accuracy of such strategies, compared with other phase-determination methods, must be assessed before their use can be advocated. In this study, we consider and explore sources of error between EM-derived haplotype frequency estimates and their population parameters, noting that much of this error is due to sampling error, which is inherent in all studies, even when phase can be determined. In light of this, we focus on the additional error between haplotype frequencies within a sample data set and EM-derived haplotype frequency estimates incurred by the estimation procedure. We assess the accuracy of haplotype frequency estimation as a function of a number of factors, including sample size, number of loci studied, allele frequencies, and locus-specific allelic departures from Hardy-Weinberg and linkage equilibrium. We point out the relative impacts of sampling error and estimation error, calling attention to the pronounced accuracy of EM estimates once sampling error has been accounted for. We also suggest that many factors that may influence accuracy can be assessed empirically within a data set-a fact that can be used to create "diagnostics" that a user can turn to for assessing potential inaccuracies in estimation.

Algorithms↗

The dynamics of living arrangements in later life: evidence from the British Household Panel Survey.

Living arrangements are a key dimension of quality of life and well-being in old age. Availability of family care, as well as social and economic support, is in part a function of whom you live with. In order to be able to forecast future changes in household composition, particularly in relation to planning and targeting particular community care services, information is needed on the probability of a person experiencing a change in their living arrangements, and the life course events that may act as triggers for such changes. This article uses data from the British Household Panel Survey (1991-99) to analyse the dynamics of living arrangements in later life.

Adult↗

Bayesian estimation of cost-effectiveness ratios from clinical trials.

Estimation of the incremental cost-effectiveness ratio (ICER) is difficult for several reasons: treatments that decrease both cost and effectiveness and treatments that increase both cost and effectiveness can yield identical values of the ICER; the ICER is a discontinuous function of the mean difference in effectiveness; and the standard estimate of the ICER is a ratio. To address these difficulties, we have developed a Bayesian methodology that involves computing posterior probabilities for the four quadrants and separate interval estimates of ICER for the quadrants of interest. We compute these quantities by simulating draws from the posterior distribution of the cost and effectiveness parameters and tabulating the appropriate posterior probabilities and quantiles. We demonstrate the method by re-analysing three previously published clinical trials.

Bayes Theorem↗

Did the loss of sigma factors initiate pseudogene accumulation in M. leprae?

Pseudogenes are non-functional regions in the genome that have arisen as a consequence of accumulating mutations that either result in the premature termination of proteins during protein synthesis or the disruption of transcription. There have been various discussions of the origins of pseudogenes and the models for their formation, but there has been little input on how pseudogenes could have accumulated in an organism. In this brief communication, I propose a two-step model for the accretion of pseudogenes in the Mycobacterium leprae genome, triggered by the loss of different sets of sigma factors at different time points during the course of evolution.

DNA-Directed RNA Polymerases↗

MIAMOD: a computer package to estimate chronic disease morbidity using mortality and survival data.

The MIAMOD package is for use in epidemiological analysis of chronic degenerative diseases. The package has been designed to use survival and mortality data supplied by the user, to estimate incidence and prevalence rates, to forecast future mortality and morbidity levels and to provide life tables. Estimates are derived by modelling incidence as an age-period-cohort function and by the equations relating specific cause mortality and prevalence to incidence and survival. The model parameters are evaluated by fitting mortality data by means of a weighted non-linear regression model. Numerical and statistical methods used to solve the regression and to compute standard errors, projections, and life tables are discussed. The program is written in standard FORTRAN 77 and runs on a mainframe computer. The different program units are illustrated together with the principal implementation options. An example of application is provided to show a typical output pattern.

Breast Neoplasms↗

Multiresolution MAP despeckling of SAR images based on locally adaptive generalized Gaussian pdf modeling.

In this paper, a new despeckling method based on undecimated wavelet decomposition and maximum a posteriori MIAP) estimation is proposed. Such a method relies on the assumption that the probability density function (pdf) of each wavelet coefficient is generalized Gaussian (GG). The major novelty of the proposed approach is that the parameters of the GG pdf are taken to be space-varying within each wavelet frame. Thus, they may be adjusted to spatial image context, not only to scale and orientation. Since the MAP equation to be solved is a function of the parameters of the assumed pdf model, the variance and shape factor of the GG function are derived from the theoretical moments, which depend on the moments and joint moments of the observed noisy signal and on the statistics of speckle. The solution of the MAP equation yields the MAP estimate of the wavelet coefficients of the noise-free image. The restored SAR image is synthesized from such coefficients. Experimental results, carried out on both synthetic speckled images and true SAR images, demonstrate that MAP filtering can be successfully applied to SAR images represented in the shift-invariant wavelet domain, without resorting to a logarithmic transformation.

Algorithms↗

Fitting the factor analysis model in lI norm.

The well-known problem of fitting the exploratory factor analysis model is reconsidered where the usual least squares goodness-of-fit function is replaced by a more resistant discrepancy measure, based on a smooth approximation of the lI norm. Fitting the factor analysis model to the sample correlation matrix is a complex matrix optimization problem which requires the structure preservation of the unknown parameters (e.g. positive definiteness). The projected gradient approach is a natural way of solving such data matching problems as especially designed to follow the geometry of the model parameters. Two reparameterizations of the factor analysis model are considered. The approach leads to globally convergent procedures for simultaneous estimation of the factor analysis matrix parameters. Numerical examples illustrate the algorithms and factor analysis solutions.

Algorithms↗

Phylogenetic relationships of fig wasps pollinating functionally dioecious Ficus based on mitochondrial DNA sequences and morphology.

The obligate mutualism between pollinating fig wasps in the family Agaonidae (Hymenoptera: Chalcidoidea) and Ficus species (Moraceae) is often regarded as an example of co-evolution but little is known about the history of the interaction, and understanding the origin of functionally dioecious fig pollination has been especially difficult. The phylogenetic relationships of fig wasps pollinating functionally dioecious Ficus were inferred from mitochondrial cytochrome oxidase gene sequences (mtDNA) and morphology. Separate and combined analyses indicated that the pollinators of functionally dioecious figs are not monophyletic. However, pollinator relationships were generally congruent with host phylogeny and support a revised classification of Ficus. Ancestral changes in pollinator ovipositor length also correlated with changes in fig breeding systems. In particular, the relative elongation of the ovipositor was associated with the repeated loss of functionally dioecious pollination. The concerted evolution of interacting morphologies may bias estimates of phylogeny based on female head characters, but homoplasy is not so strong in other morphological traits. The lesser phylogenetic utility of morphology than of mtDNA is not due to rampant convergence in morphology but rather to the greater number of potentially informative characters in DNA sequence data; patterns of nucleotide substitution also limit the utility of mtDNA findings. Nonetheless, inferring the ancestral associations of fig pollinators from the best-supported phylogeny provided strong evidence of host conservatism in this highly specialized mutualism.

Animals↗

On a non-proportional hazards regression model for repeated medical random counts.

A wholly parametric non-proportional hazards survival model is introduced. The model retains Cox's constant of proportionality as the leading term in the relative risk but permits additional flexibility by modelling the relative risk as a function of time. Covariate effects are modelled on the log odds scale, a choice which is more in keeping with the spirit of the multiple logistic function, rather than on the logarithmic scale, as in the proportional hazards model. Some basic properties of the model are described. A special feature of the model is that, when the proportional hazards model applies, Cox's regression coefficients are easily recovered and the computation of other time dependent quantities of interest is routine. A semi-Markov version of the model is derived to analyse recurrent sequential state processes and this is applied to a study of valvotomies conducted in the Regional Medical Cardiology Centre in Belfast, Northern Ireland. The results obtained are compared with those from the classical proportional hazards analysis.

Adult↗