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Monte carlo conditional inference for log-linear and logistic models: a survey of current methodology.

Nuisance parameters are parameters that are not of immediate interest to the experimenter. For log-linear and logistic models the null distribution of (most) statistics of interest depends on such parameters. Traditionally, nuisance parameters were eliminated by performing inference with respect to the chi-squared limiting distribution of common test statistics. An alternative solution is to eliminate the nuisance parameters by conditioning on their minimal sufficient statistics. The support of the resulting conditional distribution is often intractable, making null probability calculations challenging. An often feasible way to avoid complete enumeration of this support is to approximate conditional probabilities using Monte Carlo methods. In this article we survey recent developments in Monte Carlo conditional analysis for log-linear and logistic models focusing on the algorithms proposed by Booth and Butler, Diaconis and Sturmfels, Smith et al., and Mehta et al. We illustrate these algorithms with simple motivating examples.

Algorithms↗

Calculation of the proximity function of electrons.

A new semianalytical method to calculate the proximity function for electrons is proposed. An integral equation for the proximity function that can be solved by using information on the spatial dose distributions is obtained. The proximity function for electrons in the energy range from 10 eV to 10 keV is calculated by solving the equation numerically, using a set of electron collision cross sections for water vapor. The results are in good agreement with those obtained using the Monte Carlo method. The proposed method can be used for electrons of high energies much more efficiently than the Monte Carlo method.

Electrons↗

Ground-state properties of Fermi gases in the strongly interacting regime.

The ground-state energies and pairing gaps in dilute superfluid Fermi gases have now been calculated with the quantum Monte Carlo method without detailed knowledge of their wave functions. However, such knowledge is essential to predict other properties of these gases such as density matrices and pair distribution functions. We present a new and simple method to optimize the wave functions of quantum fluids using the Green's function Monte Carlo method. It is used to calculate the pair distribution functions and potential energies of Fermi gases over the entire regime from atomic Bardeen-Cooper-Schrieffer superfluid to molecular Bose-Einstein condensation, spanned as the interaction strength is varied.

Journal Article↗

Founder effect: assessment of variation in genetic contributions among founders.

We present a Monte Carlo method for determining the distribution of founders' genetic contributions to descendant cohorts. The simulation of genes through known pedigrees generates the probability distributions of contributed genes in recent cohorts of descendants, their means, and their variances. Genealogical data from three populations are analyzed: the Hutterite population of North America, the island population of Sottunga from the Aland archipelago, and the large Utah Mormon population. Two applications of the Monte Carlo method are presented. First we investigate the relative opportunity for founder effect in the three populations, which have dissimilar pedigree structures and dissimilar disease gene frequencies. Second, we measure the reproductive success of population founders in terms of the number of genes they contribute to a cohort some number of generations descendant and compare the effects of polygyny versus monogamy on reproductive success. The distribution of Hutterite founder contributions describes the context for a classic founder effect. Hutterite founders have a higher probability of leaving no genes in the population (72%) than Sottunga (48%) and Mormon (48%) founders. However, founder genes that survive among Hutterite descendants do so in larger numbers on average than founder genes in the other two populations. Greater variation among monogamous Hutterite founders compared with Mormon polygynous founders demonstrates that polygyny alone does not maximize the variance in reproductive success; other population characteristics are at least as important for determining variability among individuals in their genetic contributions to a gene pool. Our findings make it difficult to appreciate the reproductive advantage of polygyny in the Mormon population. Although the expected gene contributions and their variances were larger for polygynous founders compared with other Mormons, the main effect of polygyny was to increase the probability that any polygynist left a few genes among descendants. Furthermore, only 12% of the variation in the genetic contributions of Mormon founders is explained by their number of offspring. We conclude that shallow genealogical data (from one or a few generations) provide a poor measure of long-term reproductive success.

Alleles↗

Average glandular dose conversion coefficients for segmented breast voxel models.

For 8 voxel models of a compressed breast (4-7 cm thickness and two orientations for each thickness) and 14 radiation qualities commonly used in mammography (HVL 0.28-0.50 mm Al), tissue dose conversion coefficients were calculated for a focus-to-film distance of 60 cm using Monte Carlo methods. The voxel models were segmented from a high-resolution (slice thickness of 1 mm) computed tomography data set of an ablated breast specimen fixated while being compressed. The contents of glandular tissues amounted to 2.6%, and were asymmetrically distributed with regard to the midplane of the model. The calculated tissue dose conversion coefficients were compared with the recent literature values. These earlier tissue dose conversion coefficients were also calculated using Monte Carlo methods and breast models of various thickness, but these consist of homogeneous mixtures of glandular and adipose tissues embedded in 5 mm pure adipose tissue both at the entrance and exit sides. The results show that the new glandular tissue dose conversion coefficients agree well with the literature values for those cases where the glandular tissue is predominantly concentrated in the upper part of the model. In the opposite case, they were lower by up to 40%. These findings reveal a basic problem in patient dosimetry for mammography: glandular dose is not only governed by the average breast composition, which could be derived from the breast thickness, but also by the local distribution of glandular tissue within the breast, which is not known.

Air↗

The precision of positron emission tomography: theory and measurement.

The limits of quantitation with positron emission tomography (PET) are examined with respect to the noise propagation resulting from radioactive decay and other sources of random error. Theoretical methods for evaluating the statistical error have been devised but seldom applied to experimental data obtained on human subjects. This paper extends the analysis in several ways: (1) A Monte Carlo method is described for tracking the propagation of statistical error through the analysis of in vivo measurements; (2) Experimental data, obtained in phantoms, validating the Monte Carlo method and other methods are presented; (3) A difference in activation paradigm, performed on regional CBF (rCBF) data from five human subjects, was analyzed on 1.6-cm diameter regions of interest to determine the mean fractional statistical error in PET tissue concentration and in rCBF before and after stereotactic transformation; and (4) A linear statistical model and calculations of the various statistical errors were used to estimate the magnitude of the subject-specific fluctuations under various conditions. In this specific example, the root mean squared (RMS) noise in flow measurements was about three times higher than the RMS noise in the concentration measurements. In addition, the total random error was almost equally partitioned between statistical error and random fluctuations due to all other sources.

Brain↗

Calculation of likelihood ratio y/x in diagnosis of paternity using computer methods.

A new computational method using a Monte Carlo technique is described for the calculation of plausibility of paternity in blood group systems. In this study gene frequencies of a blood group system are simulated by the range of the seven digit random numbers. By using a Monte Carlo method, four random numbers are generated and converted into paternal and maternal genotypes. Then the genotype of the child is determined according to the law of inheritance, and finally genotypes of the father, mother and child are converted into phenotypes. Repeating this process more than one hundred thousand times, the phenotypic frequencies of child-mother-father combinations (trio) and the likelihood ratio of paternity in any blood group system are calculated for all phenotypic combinations of the trios. This method is much easier than methods reported previously, and is sufficiently accurate.

Blood Group Antigens↗

Scattering length instability in dipolar Bose-Einstein condensates.

We predict a new kind of instability in a Bose-Einstein condensate composed of dipolar particles. Namely, a comparatively weak dipole moment can produce a large, negative two-body scattering length that can collapse the Bose-Einstein condensate. To verify this effect, we validate mean-field solutions to this problem using exact, diffusion Monte Carlo methods. We show that the diffusion Monte Carlo energies are reproduced accurately within a mean-field framework if the variation of the s-wave scattering length with the dipole strength is accounted for properly.

Journal Article↗

Monte Carlo simulation of 4-alpha-glucanotransferase reaction.

4-alpha-Glucanotransferase (GTase, D-enzyme) catalyzes disproportionation between two short polymers of maltooligosaccharides linked by alpha-1,4-glucoside bonds. Using action modes of the potato GTase for the donor and acceptor substrates, the Monte Carlo method was applied to simulate the GTase reaction. The simulation starts from a single enzyme molecule and a finite number (10(5)) of substrate molecules. All selection processes were performed using random numbers produced by computer. The initial substrates were from trimer to 10-mer. In every case, the final stage was the steady-state distribution of polymers. The steady-state distribution by the potato GTase reaction was different from those by the hypothetical random disproportionation reaction. The simulated data from the reaction of potato GTase and trimer almost quantitatively agreed with experimental data. The mechanism of the GTase reaction was accumulation of probabilistic processes and was well simulated by the Monte Carlo method. GTase randomizes the overall distribution of chain length of the substrate. Therefore the GTase reaction is an entropy-driven process.

Algorithms↗

Determination of the spatial response of neutron based analysers using a Monte Carlo based method

One of the principal advantages of using thermal neutron capture (TNC, also called prompt gamma neutron activation analysis or PGNAA) or neutron inelastic scattering (NIS) techniques for measuring elemental composition is the high penetrating power of both the incident neutrons and the resultant gamma-rays, which means that large sample volumes can be interrogated. Gauges based on these techniques are widely used in the mineral industry for on-line determination of the composition of bulk samples. However, attenuation of both neutrons and gamma-rays in the sample and geometric (source/detector distance) effects typically result in certain parts of the sample contributing more to the measured composition than others. In turn, this introduces errors in the determination of the composition of inhomogeneous samples. This paper discusses a combined Monte Carlo/analytical method for estimating the spatial response of a neutron gauge. Neutron propagation is handled using a Monte Carlo technique which allows an arbitrarily complex neutron source and gauge geometry to be specified. Gamma-ray production and detection is calculated analytically which leads to a dramatic increase in the efficiency of the method. As an example, the method is used to study ways of reducing the spatial sensitivity of on-belt composition measurements of cement raw meal.

Journal Article↗

Extinction risk of a density-dependent population estimated from a time series of population size.

Environmental threats, such as habitat size reduction or environmental pollution, may not cause immediate extinction of a population but shorten the expected time to extinction. We develop a method to estimate the mean time to extinction for a density-dependent population with environmental fluctuation. We first derive a formula for a stochastic differential equation model (canonical model) of a population with logistic growth with environmental and demographic stochasticities. We then study an approximate maximum likelihood (AML) estimate of three parameters (intrinsic growth rate r, carrying capacity K, and environmental stochasticity sigma(2)(e)) from a time series of population size. The AML estimate of r has a significant bias, but by adopting the Monte Carlo method, we can remove the bias very effectively (bias-corrected estimate). We can also determine the confidence interval of the parameter based on the Monte Carlo method. If the length of the time series is moderately long (with 40-50 data points), parameter estimation with the Monte Carlo sampling bias correction has a relatively small variance. However, if the time series is short (less than or equal to 10 data points), the estimate has a large variance and is not reliable. If we know the intrinsic growth rate r, however, the estimate of K and sigma(2)(e)and the mean extinction time T are reliable even if only a short time series is available. We illustrate the method using data for a freshwater fish, Japanese crucian carp (Carassius auratus subsp.) in Lake Biwa, in which the growth rate and environmental noise of crucian carp are estimated using fishery records.

Animals↗

Favored patterns in spike trains. I. Detection.

Traditional spike-train analysis methods cannot identify patterns of firing that occur frequently but at arbitrary times. It is appropriate to search for recurring patterns because such patterns could be used for information transfer. In this paper, we present two methods for identifying "favored patterns" --patterns that occur more often than is reasonably expected at random. The quantized Monte Carlo method identifies and establishes significance for favored patterns whose detailed timing may vary but that do not have extra or missing spikes. The template method identifies favored patterns whose occurrences may have extra or missing spikes. This method is useful when employed after the results of the first method are known. Studies with simulated spike trains containing known interpolated patterns are used to establish the sensitivity and accuracy of the quantized Monte Carlo method. Certain trends with regard to parameters of the detected patterns and of the analysis methods are described. Application of these methods to neurophysiological data has shown that a large proportion of spike trains have favored patterns. These findings are described in the accompanying paper (3).

Action Potentials↗

Seasonal variation of bulk milk somatic cell counts in UK dairy herds: investigations of the summer rise.

Individual cow somatic cell count (SCC) patterns were explored over a one year period in 33 dairy herds to investigate the reason for a summer rise in bulk milk somatic cell counts (BMSCC). Cow test day somatic cell counts were categorised according to the magnitude of change since the previous test day reading, to examine which categories were responsible for the summer increase. Multilevel models using Markov chain Monte Carlo methods were specified to estimate the number of somatic cells/ml produced by different cell count categories. Stage of lactation and parity were accounted for in the models. There was an increase in the proportion of cows that remained above 200,000 cells/ml for two consecutive recordings in summer and this group of cows were responsible for 70.8% of the increase in somatic cells/ml produced from May to September compared with October to March. There was no evidence that a greater new infection rate (somatic cell counts moving from below 100,000 cells/ml to over 200,000 cells/ml) contributed to the increased summer bulk milk somatic cell counts. There was no indication that a general small increase in all somatic cell counts played an important role in the increased summer somatic cell counts. Markov chain Monte Carlo methods provided a valuable and flexible platform for parameter estimation in reasonably complex multilevel models.

Animals↗

Stochastic methods for short term projections of symptomatic HIV disease.

We designed and implemented stochastic methods for short term projections of HIV disease at the local level, that accommodate various states or stages of the disease. We gave particular attention to projection of the number of patients with HIV disease who need care, when durations of stay in these various states depend on current methods for treating opportunistic infections. We consider two types of data as input to these projections. One concerns seroprevalence surveys conducted over time and from which we can obtain time series estimates of the numbers of HIV-infected individuals. The other is a reported time series of AIDS cases adjusted for delays in reporting. Several projections, with data from the City of Philadelphia, illustrate this method. In addition, we consider a Monte Carlo method for computing confidence bounds on a projection.

Confidence Intervals↗

Investigation of photon beam output factors for conformal radiation therapy--Monte Carlo simulations and measurements.

The purpose of this study was to investigate beam output factors (OFs) for conformal radiation therapy and to compare the OFs measured with different detectors with those simulated with Monte Carlo methods. Four different detectors (diode, diamond, pinpoint and ionization chamber) were used to measure photon beam OFs in a water phantom at a depth of 10 cm with a source-surface distance (SSD) of 100 cm. Square fields with widths ranging from 1 cm to 15 cm were observed; the OF for the different field sizes was normalized to that measured at a 5 cm x 5 cm field size at a depth of 10 cm. The BEAM/EGS4 program was used to simulate the exact geometry of a 6 MV photon beam generated by the linear accelerator, and the DOSXYZ-code was implemented to calculate the OFs for all field sizes. Two resolutions (0.1 cm and 0.5 cm voxel size) were chosen here. In addition, to model the detector four kinds of material, water, air, graphite or silicon, were placed in the corresponding voxels. Profiles and depth dose distributions resulting from the simulation show good agreement with the measurements. Deviations of less than 2% can be observed. The OF measured with different detectors in water vary by more than 35% for 1 cm x 1 cm fields. This result can also be found for the simulated OF with different voxel sizes and materials. For field sizes of at least 2 cm x 2 cm the deviations between all measurements and simulations are below 3%. This demonstrates that very small fields have a bad effect on dosimetric accuracy and precision. Finally, Monte Carlo methods can be significant in determining the OF for small fields.

Humans↗

Hybrid Monte Carlo-diffusion method for light propagation in tissue with a low-scattering region.

The heterogeneity of the tissues in a head, especially the low-scattering cerebrospinal fluid (CSF) layer surrounding the brain has previously been shown to strongly affect light propagation in the brain. The radiosity-diffusion method, in which the light propagation in the CSF layer is assumed to obey the radiosity theory, has been employed to predict the light propagation in head models. Although the CSF layer is assumed to be a nonscattering region in the radiosity-diffusion method, fine arachnoid trabeculae cause faint scattering in the CSF layer in real heads. A novel approach, the hybrid Monte Carlo-diffusion method, is proposed to calculate the head models, including the low-scattering region in which the light propagation does not obey neither the diffusion approximation nor the radiosity theory. The light propagation in the high-scattering region is calculated by means of the diffusion approximation solved by the finite-element method and that in the low-scattering region is predicted by the Monte Carlo method. The intensity and mean time of flight of the detected light for the head model with a low-scattering CSF layer calculated by the hybrid method agreed well with those by the Monte Carlo method, whereas the results calculated by means of the diffusion approximation included considerable error caused by the effect of the CSF layer. In the hybrid method, the time-consuming Monte Carlo calculation is employed only for the thin CSF layer, and hence, the computation time of the hybrid method is dramatically shorter than that of the Monte Carlo method.

Adult↗

Fast LROC analysis of Bayesian reconstructed emission tomographic images using model observers.

Lesion detection and localization is an important task in emission computed tomography. Detection and localization performance with signal location uncertainty may be summarized by a scalar figure of merit, the area under the localization receiver operating characteristic (LROC) curve, A(LROC). We consider model observers to compute A(LROC) for two-dimensional maximum a posteriori (MAP) reconstructions. Model observers may be used to rapidly prototype studies that use human observers. We address the case background-known-exactly (BKE) and signal known except for location. Our A(LROC) calculation makes use of theoretical expressions for the mean and covariance of the reconstruction and, unlike conventional methods that also use model observers, does not require computation of a large number of sample reconstructions. We validate the results of the procedure by comparison to A(LROC) obtained using a gold-standard Monte Carlo method employing a large set of reconstructed noise samples. Under reasonable simulation conditions, our theoretical calculation is about one to two orders of magnitude faster than the conventional Monte Carlo method.

Algorithms↗

Analytic microdosimetry for radioimmunotherapeutic alpha emitters.

Analytic microdosimetry using Fourier transform techniques has been applied to internal alpha emitters. These techniques need revision and simplification for use with short-lived radionuclides such as those which may be useful for radioimmunotherapy. Analytic methods may have advantages over Monte Carlo methods in some cases (e.g., where time is important). Applications to eight different source geometries show the usefulness of these techniques. Comparisons of some of the results of Monte Carlo calculations prove its accuracy. For a uniform source of 5.867-MeV alphas spread throughout the volume outside a cell surface, the two methods agree well. Results are within 1% both for the average specific energy and for the number of hits. Analytic microdosimetry provides an alternate method to use for the critical evaluation of models that seek to predict the relation between alpha energy deposition and cell survival data. Similarly, it may be helpful to point the way toward the rational interpretation of general biological results for antibodies labeled with alpha emitters.

Alpha Particles↗