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PubMed2002

Stages of change among ethnically diverse college students.

The authors applied the stage-of-change construct in the transtheoretical model to examine the distribution of Asian (n = 869), African American (n = 373), White (n = 1322), and Hispanic (n = 535) American undergraduate students across the 5 stages of change for exercise. Stage of change varied as a function of ethnicity. Higher percentages of minorities were in the precontemplation and contemplation stages. The likelihood of being in these stages was from 43% to 82% greater for minorities than for White students. Also examined were the congruency between stage of change and self-reported levels of physical activity. Half of the sedentary students and 15.6% of the active students were misclassified by the stage-of-change procedure. Misclassification rates were higher for minority women (27.8%) than for White women (17.8%) and for Asian students (24.6%) compared with all others (20.6%). The results of this study have implications for the design of physical activity interventions based on stage of change.

Adolescent↗
PubMed2001

Estimation for paired binomial data with application to radiation therapy.

We compare and contrast several different methods for estimating the effect of treatment when responses are paired binomial observations. The ratio of binomial probabilities is the parameter of interest, while the binomial probabilities are nuisance parameters which may vary between pairs. The application is a meta-analysis of the treatment of rectal cancer, with observations in each study indicating the number of recurrences of the cancer in each of two groups, one with radiation therapy and one without. The ratio of the probabilities of recurrence in the radiation to non-radiation groups is of substantive interest, and is modelled as a logistic or complementary log-log function of an unknown linear combination of the covariates. The three methods we consider are maximum likelihood, a Bayesian approach and an approach based on estimating equations. For the MLE and Bayesian approach the potentially large number of nuisance parameters are estimated together with the parameters of interest, whereas for the estimating equation approach only the parameters of interest are estimated. A simulation study is performed to compare the methods and evaluate the impact of overdispersion.

Bayes Theorem↗
PubMed2024

Leveraging clinical intuition to improve accuracy of phenotype-driven prioritization.

PURPOSE: Clinical intuition is commonly incorporated into the differential diagnosis as an assessment of the likelihood of candidate diagnoses based either on the patient population being seen in a specific clinic or on the signs and symptoms of the initial presentation. Algorithms to support diagnostic sequencing in individuals with a suspected rare genetic disease do not yet incorporate intuition and instead assume that each Mendelian disease has an equal pretest probability. METHODS: The LIkelihood Ratio Interpretation of Clinical AbnormaLities (LIRICAL) algorithm calculates the likelihood ratio of clinical manifestations represented by Human Phenotype Ontology terms to rank candidate diagnoses. The initial version of LIRICAL assumed an equal pretest probability for each disease in its calculation of the posttest probability (where the test is diagnostic exome or genome sequencing). We introduce Clinical Intuition for Likelihood Ratios (ClintLR), an extension of the LIRICAL algorithm that boosts the pretest probability of groups of related diseases deemed to be more likely. RESULTS: The average rank of the correct diagnosis in simulations using ClintLR showed a statistically significant improvement over a range of adjustment factors. CONCLUSION: ClintLR successfully encodes clinical intuition to improve ranking of rare diseases in diagnostic sequencing. ClintLR is freely available at https://github.com/TheJacksonLaboratory/ClintLR.

Humans↗
PubMed1999

Local EM estimation of the hazard function for interval-censored data.

We propose a smooth hazard estimator for interval-censored survival data using the method of local likelihood. The model is fit using a local EM algorithm. The estimator is more descriptive than traditional empirical estimates in regions of concentrated information and takes on a parametric flavor in regions of sparse information. We derive two different standard error estimates for the smooth curve, one based on asymptotic theory and the other on the bootstrap. We illustrate the local EM method for times to breast cosmesis deterioration (Finkelstein, 1986, Biometrics 42, 845-854) and for times to HIV-1 infection for individuals with hemophilia (Kroner et al., 1994, Journal of AIDS 7, 279-286). Our hazard estimates for each of these data sets show interesting structures that would not be found using a standard parametric hazard model or empirical survivorship estimates.

Algorithms↗
PubMed2003

A simple approach to fitting Bayesian survival models.

There has been much recent work on Bayesian approaches to survival analysis, incorporating features such as flexible baseline hazards, time-dependent covariate effects, and random effects. Some of the proposed methods are quite complicated to implement, and we argue that as good or better results can be obtained via simpler methods. In particular, the normal approximation to the log-gamma distribution yields easy and efficient computational methods in the face of simple multivariate normal priors for baseline log-hazards and time-dependent covariate effects. While the basic method applies to piecewise-constant hazards and covariate effects, it is easy to apply importance sampling to consider smoother functions.

Bayes Theorem↗
PubMed2002

An application of the technique of density estimation in geographical epidemiology of goitre in the Muzaffarpur district of Bihar state of India.

The Gangetic plains in the Sub-Himalayan belt of India are known endemic areas for goitre. The districts of Muzaffarpur and Sitamarhi in the eastern zone in the Bihar state of India showed a prevalence of over 30 per cent of goitre in a survey conducted by the Indian Council of Medical Research (ICMR) during 1983-1986. In the present paper, the technique of density estimation is employed to estimate the probability density functions of goitre-affected and normal (non-goitre) populations of the district of Muzaffarpur. The likelihood ratio is then plotted against distance of the villages from the Indo-Nepal border keeping their distances from the headquarters in the district of Sitamarhi at fixed level. Using the odds form of Bayes rule, the posterior odds of goitre are calculated and compared at two given points.

Bayes Theorem↗
PubMed2000

Fluctuating mutation bias and the evolution of base composition in Drosophila.

The idea that the pattern of point mutation in Drosophila has remained constant during the evolution of the genus has recently been challenged. A study of the nucleotide composition focused on the Drosophila saltans group has evidenced unsuspected nucleotide composition differences among lineages. Compositional differences are associated with an accelerated rate of amino acid replacement in functionally less constrained regions. Here we reassess this issue from a different perspective. Adopting a maximum-likelihood estimation approach, we focus on the different predictions that mutation and selection make about the nonsynonymous-to-synonymous rate ratio. We investigate two gene regions, alcohol dehydrogenase (Adh) and xanthine dehydrogenase (Xdh), using a balanced data set that comprises representatives from the melangaster, obscura, saltans, and willistoni groups. We also consider representatives of the Hawaiian picture-winged group. These Hawaiian species are known to have experienced repeated bottlenecks and are included as a reference for comparison. Our results confirm patterns previously detected. The branch ancestral to the fast-evolving willistoni/saltans lineage, where most of the change in GC content has occurred, exhibits an excess of synonymous substitutions. The shift in mutation bias has affected the extent of the rate variation among sites in Xdh.

Alcohol Dehydrogenase↗
PubMedDate not supplied

A statistical approach to computer processing of cryo-electron microscope images: virion classification and 3-D reconstruction.

The scattering density of the virus is represented as a truncated weighted sum of orthonormal basis functions in spherical coordinates, where the angular dependence of each basis function has icosahedral symmetry. A statistical model of the image formation process is proposed and the maximum likelihood estimation method computed by an expectation-maximization algorithm is used to estimate the weights in the sum and thereby compute a 3-D reconstruction of the virus particle. If multiple types of virus particle are represented in the boxed images then multiple 3-D reconstructions are computed simultaneously without first requiring that the type of particle shown in each boxed image be determined. Examples of the procedure are described for viruses with known structure: (1). 3-D reconstruction of Flockhouse Virus from experimental images, (2). 3-D reconstruction of the capsid of Nudaurelia Omega Capensis Virus from synthetic images, and (3). 3-D reconstruction of both the capsid and the procapsid of Nudaurelia Omega Capensis Virus from a mixture of unclassified synthetic images.

Algorithms↗
PubMed1997

Intestinal motility during hypoxia and reoxygenation in vitro.

Ischemia-reperfusion injury leads to profound functional and structural alterations of the gastrointestinal tract. We developed an in vitro model of reperfusion injury to study the changes in intestinal motility during hypoxia followed by reoxygenation. We recorded the spontaneous motor activity of intestinal rings from the proximal mouse jejunum, using force displacement transducers. In addition to the rhythmic contractions, we studied the contractile response to transmural stimulation of intrinsic nerves. During hypoxia, the frequency of the spontaneous contractions and the resting tension decreased. While 29% of the tissues still responded to neural stimulation after 15 min of hypoxia, electrical field stimulation did not evoke any response after 60 min of hypoxia. Reoxygenation resulted in a transient increase in the baseline tension and an initial normalization of the spontaneous rhythmic contractions, which subsequently became irregular. The percentage of tissues that recovered their ability to respond to electrical field stimulation 10 min after reoxygenation decreased from 100% after 15 min of hypoxia to 47% after 60 min of hypoxia. The administration of the antioxidant glutathione prevented the functional abnormalities seen 10 min after reoxygenation. The pharmacological inhibition of Cu,Zn superoxide dismutase exacerbated the functional reoxygenation damage. Conversely, the overexpression of this radical-scavenging enzyme in transgenic mice increased the likelihood of functional recovery. Reoxygenation in a calcium-free solution also prevented prolonged functional damage of the muscle rings. We conclude that hypoxia-reoxygenation significantly alters intestinal motility. The generation of reactive oxygen species and disruptions in the calcium homeostasis play an important role in the pathogenesis of reoxygenation damage. Interventions that alter the intracellular redox state or affect the secondary changes in the intracellular calcium concentration can prevent or blunt the effects of reoxygenation injury on intestinal motility.

Animals↗
PubMed2006

Short-term synaptic plasticity can enhance weak signal detectability in nonrenewal spike trains.

We study the encoding of weak signals in spike trains with interspike interval (ISI) correlations and the signals' subsequent detection in sensory neurons. Motivated by the observation of negative ISI correlations in auditory and electrosensory afferents, we assess the theoretical performance limits of an individual detector neuron receiving a weak signal distributed across multiple afferent inputs. We assess the functional role of ISI correlations in the detection process using statistical detection theory and derive two sequential likelihood ratio detector models: one for afferents with renewal statistics; the other for afferents with negatively correlated ISIs. We suggest a mechanism that might enable sensory neurons to implicitly compute conditional probabilities of presynaptic spikes by means of short-term synaptic plasticity. We demonstrate how this mechanism can enhance a postsynaptic neuron's sensitivity to weak signals by exploiting the correlation structure of the input spike trains. Our model not only captures fundamental aspects of early electrosensory signal processing in weakly electric fish, but may also bear relevance to the mammalian auditory system and other sensory modalities.

Action Potentials↗
PubMed2000

Recognizing transient low-frequency whale sounds by spectrogram correlation.

A method is described for the automatic recognition of transient animal sounds. Automatic recognition can be used in wild animal research, including studies of behavior, population, and impact of anthropogenic noise. The method described here, spectrogram correlation, is well-suited to recognition of animal sounds consisting of tones and frequency sweeps. For a sound type of interest, a two-dimensional synthetic kernel is constructed and cross-correlated with a spectrogram of a recording, producing a recognition function--the likelihood at each point in time that the sound type was present. A threshold is applied to this function to obtain discrete detection events, instants at which the sound type of interest was likely to be present. An extension of this method handles the temporal variation commonly present in animal sounds. Spectrogram correlation was compared to three other methods that have been used for automatic call recognition: matched filters, neural networks, and hidden Markov models. The test data set consisted of bowhead whale (Balaena mysticetus) end notes from songs recorded in Alaska in 1986 and 1988. The method had a success rate of about 97.5% on this problem, and the comparison indicated that it could be especially useful for detecting a call type when relatively few (5-200) instances of the call type are known.

Animals↗
PubMed2001

Genetic evaluation of dairy cattle using test-day models.

Recently there has been considerable interest in modeling individual test-day records (TDR) for genetic evaluation of dairy cattle as a replacement for the traditional use of estimated accumulated 305-d yields. Some advantages of test-day models (TDM) include the ability to account for environmental effects of each test day, the ability to model the trajectory of the lactation for individual genotypes or groups of animals, and the possibility of genetic evaluations for persistency of production. Also, the use of test-day models avoids the necessity of extending short lactations on culled animals and animals with records in progress. The disadvantages of TDM include computational difficulties associated with analyzing much larger datasets and the need to estimate many more parameters than in a traditional 305-d lactation model. Several different models have been proposed to model the trajectory of the lactation, including so-called "biological functions," various polynomials and character process models. At present, there is not universal agreement on which models to use in routine prediction of breeding values and better methods to compare models are desirable. Obtaining accurate estimates of the dispersion parameters to use in TDM remains a challenge. Methods used include a two-step procedure in which the dispersion parameters are estimated in a series of multivariate models followed by a reduction in order of fit using covariance functions, and a one-step procedure in which the parameters of TDM are estimated using restricted maximum likelihood or Bayesian methods in a random regression model. Further research should focus on including multiple lactation data and accounting for heterogeneity variance.

Algorithms↗
PubMed2004

Left atrial volume in the prediction of first ischemic stroke in an elderly cohort without atrial fibrillation.

OBJECTIVE: To determine the clinical importance of left atrial (LA) volume in the prediction of first ischemic stroke. PATIENTS AND METHODS: This retrospective cohort study included randomly selected residents of Olmsted County, Minnesota, aged 65 years or older, who had undergone transthoracic echocardiography at least once at the Mayo Clinic in Rochester, Minn, between January 1, 1990, and December 31, 1998, were in sinus rhythm, and had no history of stroke, transient ischemic attack, atrial fibrillation, or valvular heart disease. Patients were monitored through medical records for first ischemic stroke or death. RESULTS: Of 1554 residents (59% women) aged 75+/-7 years, 92 (6%) had experienced at least 1 ischemic stroke over 4.3+/-2.7 years (incident stroke rate, 1.4 per 100 person-years). Left atrial volume of 32 mL/m2 or greater (hazard ratio [HR], 1.63; confidence interval [CI], 1.08-2.46) was independent of age (HR, 1.04; CI, 1.02-1.07), diabetes (HR, 1.91; CI, 1.07-3.41), myocardial infarction (HR, 1.64; CI, 1.01-2.64), and hyperlipidemia (HR, 1.55; CI, 1.01-2.37) for the prediction of first ischemic stroke. When quartiles of LA dimension were plotted against quartiles of indexed LA volume, a stepwise increase in risk with each quartile increment was evident only for indexed LA volume. Also, an LA volume of 32 mL/m2 or greater was associated with an increased mortality risk (HR, 1.30; CI, 1.09-1.56), independent of age, sex, and stroke status. CONCLUSIONS: In our elderly cohort with no prior atrial fibrillation, LA volume was independently predictive of first ischemic stroke, incremental to age, diabetes, myocardial infarction, and hyperlipidemia. It was also an independent predictor of death.

Aged↗
PubMed2000

[Statistical analysis in the evaluation of controlled diffusion of iodine in the water in developing countries].

This report describes the methodology and findings of a novel statistical technique for evaluation of the efficacy of the Rhodifuse Iode system in prevention of endemic goiter in Mali. The system involves continuous release of iodine in ground water used for drinking. Study was carried out in four villages for one year. The iodine release system was used in three villages. The fourth village served as the control. The incidence of goiter graded using the criteria of the WHO was assessed in each village according to sex. Statistical analysis consisted of correlating goiter grade with four predictors, i.e., village, sex, iodine release, and time. Since goiter grade is a dependent variable, its law of probability was modeled in function of the predictors. The Cat Mot procedure included in the SAS software package allowed both definition of the law of probability of grade of goiter and its transformation in function of predictor. The generalized linear model was obtained by either the generalized least square method or greatest likelihood method. The Proc Catmod procedure was then used to generalize analysis of variance in case of a nominal or ordinal, binary or polytomic response. The results of this novel statistical technique suggested that the Rhodifuse Iode system was effective.

Adult↗
PubMed2004

A haplotype-based test of association using data from cohort and nested case-control epidemiologic studies.

Haplotype-based risk models can lead to powerful methods for detecting the association of a disease with a genomic region of interest. In population-based studies of unrelated individuals, however, the haplotype status of some subjects may not be discernible without ambiguity from available locus-specific genotype data. A score test for detecting haplotype-based association using genotype data has been developed in the context of generalized linear models for analysis of data from cross-sectional and retrospective studies. In this article, we develop a test for association using genotype data from cohort and nested case-control studies where subjects are prospectively followed until disease incidence or censoring (end of follow-up) occurs. Assuming a proportional hazard model for the haplotype effects, we derive an induced hazard function of the disease given the genotype data, and hence propose a test statistic based on the associated partial likelihood. The proposed test procedure can account for differential follow-up of subjects, can adjust for possibly time-dependent environmental co-factors and can make efficient use of valuable age-at-onset information that is available on cases. We provide an algorithm for computing the test statistic using readily available statistical software. Utilizing simulated data in the context of two genomic regions GPX1 and GPX3, we evaluate the validity of the proposed test for small sample sizes and study its power in the presence and absence of missing genotype data.

Algorithms↗