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PubMed2002

The role of quantitative (18)F-FDG PET studies for the differentiation of malignant and benign bone lesions.

UNLABELLED: The role of quantitative (18)F-FDG PET studies for the differentiation of benign and malignant bone lesions is still an open question. METHODS: Our evaluation included 83 patients with 37 histologically proven malignancies and 46 benign lesions. Thirty-five of the 46 benign lesions were histologically confirmed. The (18)F-FDG studies were accomplished as a dynamic series for 60 min. Evaluation of the (18)F-FDG kinetics was performed using the following parameters: standardized uptake value (SUV), global influx (Ki), computation of the transport constants K1-k4 with consideration of the distribution volume (VB) according to a 2-tissue-compartment model, fractal dimension based on the box-counting procedure (parameter for the inhomogeneity of the tumors). RESULTS: The mean SUV, the vascular fraction VB, K1, and k3 were higher in malignant tumors compared with benign lesions (t test; P < 0.05). Although the (18)F-FDG SUV was helpful to differentiate benign and malignant tumors, there was some overlap, which limited the diagnostic accuracy. On the basis of the discriminant analysis, the SUV alone showed a sensitivity of only 54.05%, a specificity of 91.30%, and a diagnostic accuracy of 74.70%. The fractal dimension was superior and showed a sensitivity of 71.88%, a specificity of 81.58%, and an accuracy of 77.14%. The combination of SUV, fractal dimension, VB, K1-k4, and Ki revealed the best results with a sensitivity of 75.86%, a specificity of 97.22%, and an accuracy of 87.69%. Bayesian analysis showed true-positive results at the level of 0.8 for a low prevalence of disease (0.235) if the full kinetic data were used in the evaluation. CONCLUSION: (18)F-FDG PET has a high specificity for the exclusion of a malignant bone tumor. Evaluation of the full (18)F-FDG kinetics and the application of discriminant analysis are required and can be used prospectively to classify a bone lesion as malignant or benign.

Bayes Theorem↗

PubMed2004

[The risk of cancer in inhabitants of Weurt, the Netherlands].

OBJECTIVE: To analyze the risk of cancer in the population of Weurt, a village near Nijmegen, the Netherlands, using long-term data (13 years). DESIGN: Cluster analysis. METHOD: Anonymous data on newly diagnosed cases of cancer in the years 1989-2001 were obtained from the regional cancer registry. The region had about 1 million inhabitants and 263 postal code areas. The Dutch Central Statistical Office (Statistics Netherlands) provided age- and sex-specific population data for each postal code area. Ratios of observed and expected numbers of cancer cases were calculated (uncorrected standardized mortality ratio; SMR). A Bayesian analysis with a random effects model with spatial correlation was used to adjust the SMRs for cancer incidence in neighbouring postal code areas. RESULTS: In the years 1989-2001, a total number of 167 cases of cancer (97 in males and 70 in females) were diagnosed in Weurt. The number of cancers in the entire area was 58,126. In Weurt the adjusted SMR for all cancers was 1.18 (95% CI: 0.95-1.44) in males and 1.10 (95% CI: 0.86-1.39) in females. For lung cancer the adjusted SMR was 1.35 (95% CI: 0.88-1.94) in males and 1.00 (95% CI: 0.29-2.13) in females. None of the other types of cancer showed a statistically significant increase in incidence in Weurt. CONCLUSIONS: Although based on relatively small numbers of diagnosed cancers, these results are not suggestive of a real cancer cluster in Weurt. Lung cancer incidence was slightly increased in males and not in females, which may indicate that chance, lifestyle or occupational factors were more obvious causes than environmental factors. In general, it is advised to be reluctant to perform cluster analyses. Such analyses may only be valuable if specific hypotheses regarding causes of specific types of cancer are present.

Adult↗

PubMed2003

Estimating allelic number and identity in state of QTLs in interconnected families.

When multiple related families derived from inbred lines are jointly analysed to detect quantitative trait loci (QTLs), the analysis should estimate allelic effects as accurately as possible and estimate the probability that different parents carry alleles that are identical in state. Analyses exist that assume that all parents carry unique alleles or that all parents but one carry the same allele. In practice, many configurations are possible that group different parents according to their identity-in-state condition at a putative QTL allele. Here, we propose a variable model Bayesian analysis that selects among possible identity-in-state configurations and jointly estimates the allelic effects of identical-in-state parents. We contrast this analysis with a fixed model analysis that estimates unique allelic effects for all parents. We analyse two simulated mating designs: an experimental design in which three inbred parents were crossed to generate two families of 150 doubled haploid lines; and a breeding design in which 20 inbred parents were crossed to generate 60 families of 20 doubled haploid lines, with each parent contributing to six families. In all cases where some parents were simulated to carry alleles of identical effect (that is, they were identical in state), the variable analysis estimated allelic effects with lower mean-squared error than the fixed analysis. The variable analysis showed that, unless each family contains many individuals (more than 100), there is insufficient information in DNA-marker and phenotypic data to determine with high probability the QTL allelic number.

Bayes Theorem↗

PubMed2005

Predictive value of fetal pulmonary venous flow patterns in identifying the need for atrial septoplasty in the newborn with hypoplastic left ventricle.

BACKGROUND: Pulmonary venous Doppler (PVD) flow patterns in the fetus with hypoplastic left heart syndrome (HLHS) have been correlated with restrictive interatrial communication or intact atrial septum (RAS) postnatally; however, the ability of PVD to identify the neonate requiring emergent atrial septoplasty (EAS) for severe left atrial hypertension and hypoxemia has not been critically evaluated. It was the purpose of this study to determine the predictive power of fetal PVD in identifying the need for EAS in newborns with HLHS and RAS. METHODS AND RESULTS: Forty-one patients with fetal PVD flow analysis and postnatally confirmed HLHS were studied. Pulsed-wave assessment of PVD flow included S-, D-, and A-wave velocity, time-velocity integral (VTI) of forward and reverse flow, and S/D velocity and forward/reverse VTI ratio. Neonatal EAS was used as the primary clinical outcome variable. Receiver operating characteristic curves were used to determine cutpoints at which PVD indices best predicted EAS. Cutpoints were evaluated for clinical accuracy and usefulness by use of Bayesian analysis. Eight of 41 subjects underwent EAS. Need for EAS was most accurately predicted by forward/reverse VTI ratio <5 (sensitivity, 0.88, 95% CI, 0.49 to 0.99; specificity, 0.97, 95% CI, 0.82 to 0.99), which, when present, increases the posttest likelihood of EAS to 74%, assuming a pretest prevalence of 10%. Accuracy and usefulness of other PVD indices were affected by false-positive results. CONCLUSIONS: In the fetus with HLHS, a PVD forward/reverse VTI ratio of <5 is the strongest predictor of the need for EAS in the newborn period. These observations should improve our ability to identify and expectantly manage the fetus with HLHS and RAS.

Angioplasty↗

PubMed2000

Bayesian inference for kappa from single and multiple studies.

Cohen's kappa coefficient is a widely popular measure for chance-corrected nominal scale agreement between two raters. This article describes Bayesian analysis for kappa that can be routinely implemented using Markov chain Monte Carlo (MCMC) methodology. We consider the case of m > or = 2 independent samples of measured agreement, where in each sample a given subject is rated by two rating protocols on a binary scale. A major focus here is on testing the homogeneity of the kappa coefficient across the different samples. The existing frequentist tests for this case assume exchangeability of rating protocols, whereas our proposed Bayesian test does not make any such assumption. Extensive simulation is carried out to compare the performances of the Bayesian and the frequentist tests. The developed methodology is illustrated using data from a clinical trial in ophthalmology.

Bayes Theorem↗

PubMed1988

Predicting serum lithium concentration using Bayesian method: a comparison with other methods.

Two pharmacokinetic approaches (single-point Bayesian and two fixed volume of distribution-iterative methods) for predicting serum lithium concentrations in patients treated with lithium carbonate for manic-depressive illness or cyclic neutropenia in Kyushu University Hospital were evaluated and compared retrospectively. Prior to these analyses, three methods (prediction using mean parameters reported by Mason et al., the Pepin method, and the Zetin method) without measuring serum concentrations were also compared. In the Bayesian analysis, the effect of population mean parameters (reported by Mason et al. and Pepin et al.), which were used as initial estimates in a fitting process, on predictive performance was also studied. Forty five patients (21 male, 24 female) were included in this study. The average number of determinations per patient was 6.3, and the sampling times ranged from 2 to 18 h after the last dose. Serum lithium concentrations were measured by atomic absorption spectrometer. The Bayesian method used a computer program (PEDA) developed previously by one of us. The prediction using the population mean values from Mason's report gave the least root mean squared error (RMSE; a composite measure for bias and precision of prediction), and was considered to be the most precise among the methods without measuring serum concentrations. Among the methods using a single measured concentration, the Bayesian prediction was less biased and more precise than that by the two fixed volume of distribution-iterative methods. The Bayesian method reduced prediction error in serum concentration prediction compared with those obtained from population mean parameters in both cases: A high reduction of RMSE was observed when the values from Pepin method were used as initial estimates (from 0.320 to 0.219 meq/l), while, Mason's values gave less reduction (from 0.219 to 0.213 meq/l). In the Bayesian prediction of serum lithium concentration, the selection of population-based initial estimates gave no effect on predictive ability of the Bayesian method in terms of RMSE. In conclusion, the Bayesian method was robust and flexible with regard to dosing schedule, sampling time and number of blood samples, and gave the most clinically acceptable precision among the methods evaluated.

Adolescent↗

PubMedDate not supplied

[The retrospective cytogenetic dosimetry using the results of conventional chromosomal analysis in Chernobyl clean-up workers].

The paper presents the results of the cohortal biodosimetry carried out in 435 Chernobyl clean-up workers, who were surveyed with the conventional cytogenetic technique in terms from several days to 10 years after the end of their duties in the Chernobyl accident exclusive zone. An empirical model of the aberrant cell dynamics was utilized for the calculation of mean initial yields of dicentrics and centric rings in groups with different terms and duration of staying in the Chernobyl zone. Corresponding protracted irradiation doses estimated from aberration levels ranged from 79 to 670 mGy. The probabilistic distribution of the radiation doses was constructed by the applying the Bayesian analysis to initial individual chromosome exchange yields extrapolated to the exposure termination moment. This distribution was characterized by the mean dose about 460 mGy and maximum of probability density in the interval of 50-300 mGy. For the late somatic risk assessment in clean-up workers the probabilistic distribution of equivalentally-acute radiation doses was proposed; that had the mean value about 270 mGy, modal classes of 250-350 mGy and 99.8% of the probability density concentrated within the dose range from 0 to 1000 mGy.

Adult↗

PubMed2006

Phylogeny and biogeography of the Petaurista philippensis complex (Rodentia: Sciuridae), inter- and intraspecific relationships inferred from molecular and morphometric analysis.

With modified DNA extraction and purification protocols, the complete cytochrome b gene sequences (1140 bp) were determined from degraded museum specimens. Molecular analysis and morphological examination of cranial characteristics of the giant flying squirrels of Petaurista philippensis complex (P. grandis, P. hainana, and P. yunanensis) and other Petaurista species yielded new insights into long-standing controversies in the Petaurista systematics. Patterns of genetic variations and morphological differences observed in this study indicate that P. hainana, P. albiventer, and P. yunanensis can be recognized as distinct species, and P. grandis and P. petaurista are conspecific populations. Phylogenetic relationships reconstructed by using parsimony, likelihood, and Bayesian methods reveal that, with P. leucogenys as the basal branch, all Petaurista groups formed two distinct clades. Petaurista philippensis, P. hainana, P. yunanensis, and P. albiventer are clustered in the same clade, while P. grandis shows a close relationship to P. petaurista. Deduced divergence times based on Bayesian analysis and the transversional substitution at the third codon suggest that the retreating of glaciers and upheavals or movements of tectonic plates in the Pliocene-Pleistocene were the major factors responsible for the present geographical distributions of Petaurista groups.

Animals↗

PubMed2002

Genetic consequences of sequential founder events by an island-colonizing bird.

The importance of founder events in promoting evolutionary changes on islands has been a subject of long-running controversy. Resolution of this debate has been hindered by a lack of empirical evidence from naturally founded island populations. Here we undertake a genetic analysis of a series of historically documented, natural colonization events by the silvereye species-complex (Zosterops lateralis), a group used to illustrate the process of island colonization in the original founder effect model. Our results indicate that single founder events do not affect levels of heterozygosity or allelic diversity, nor do they result in immediate genetic differentiation between populations. Instead, four to five successive founder events are required before indices of diversity and divergence approach that seen in evolutionarily old forms. A Bayesian analysis based on computer simulation allows inferences to be made on the number of effective founders and indicates that founder effects are weak because island populations are established from relatively large flocks. Indeed, statistical support for a founder event model was not significantly higher than for a gradual-drift model for all recently colonized islands. Taken together, these results suggest that single colonization events in this species complex are rarely accompanied by severe founder effects, and multiple founder events and/or long-term genetic drift have been of greater consequence for neutral genetic diversity.

Animals↗

PubMed1987

Evaluation of a Bayesian regression-analysis computer program using non-steady-state phenytoin concentrations.

The predictive performance of a Bayesian regression-analysis computer program that uses non-steady-state phenytoin data was evaluated. Forty patients receiving phenytoin or phenytoin sodium who had two or more non-steady-state serum concentrations were selected for study. Additional serum concentrations and dosing data were collected as they became available, but no effort was made to control the number or timing of serum concentration determinations. Patients were categorized into four groups for evaluation of the effect of potential bioavailability problems and length of dosing history (time over which serum concentration-time data were collected) on the ability to predict subsequent phenytoin concentrations. Population parameters for phenytoin maximum rate of elimination (Vmax), apparent Michaelis-Menten constant (Km), volume of distribution (V), and bioavailability (F) were obtained from the literature. Predictions based on serum phenytoin concentrations and dosing histories (information intervals) of 5 or 10 days were compared with predictions based on naive (population-based) estimates using prediction-error analysis. In each patient group, the use of either 5-day or 10-day information intervals resulted in a significant increase in precision and a significant reduction in bias compared with naive estimates. For the group of patients who initially had two or more serum concentrations within the first five days of monitoring, predictions showed a marked increase in bias and a decrease in precision as the time interval from the last measured concentration to the time of prediction increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Bayes Theorem↗

PubMed1993

Germ-line origins of mutation in families with hemophilia B: the sex ratio varies with the type of mutation.

Previous epidemiological and biochemical studies have generated conflicting estimates of the sex ratio of mutation. Direct genomic sequencing in combination with haplotype analysis extends previous analyses by allowing the precise mutation to be determined in a given family. From analysis of the factor IX gene of 260 consecutive families with hemophilia B, we report the germ-line origin of mutation in 25 families. When combined with 14 origins of mutation reported by others and with 4 origins previously reported by us, a total of 25 occur in the female germ line, and 18 occur in the male germ line. The excess of germ-line origins in females does not imply an overall excess mutation rate per base pair in the female germ line. Bayesian analysis of the data indicates that the sex ratio varies with the type of mutation. The aggregate of single-base substitutions shows a male predominance of germ-line mutations (P < .002). The maximum-likelihood estimate of the male predominance is 3.5-fold. Of the single-base substitutions, transitions at the dinucleotide CpG show the largest male predominance (11-fold). In contrast to single-base substitutions, deletions display a sex ratio of unity. Analysis of the parental age at transmission of a new mutation suggests that germ-line mutations are associated with a small increase in parental age in females but little, if any, increase in males. Although direct genomic sequencing offers a general method for defining the origin of mutation in specific families, accurate estimates of the sex ratios of different mutational classes require large sample sizes and careful correction for multiple biases of ascertainment. The biases in the present data result in an underestimate of the enhancement of mutation in males.

Adolescent↗

PubMed2000

Theophylline pharmacokinetics with concomitant steroid and gold therapy.

BACKGROUND: Theophylline has been used for several decades in the treatment of asthma. In recent years, however, with the appreciation of the importance of inflammation in the pathogenesis of asthma, new therapeutic approaches have arisen, including beta2-agonists, steroid and nonsteroidal anti-inflammatory drugs, such as gold salts. OBJECTIVE: In the present work we studied the kinetic behaviour of theophylline administered concomitantly with methylprednisolone (steroid compound) and auranofin (oral gold) in six adult female patients. METHOD: Drug concentration data for patients under routine care were collected. The kinetic analysis (Bayesian Approach) was done using two different commercial software packages, PKS (Abbott Diagnostics) and CAPCIL (SIMKIN Inc., courtesy of Dade-Behring). A one-compartment open model with first-order absorption (ka for PKS=0. 5/h; ka for CAPCIL=0.3/h ) and first- order elimination. Default CL, t1/2 and Vd values were used for each program was assumed. The measured and predicted theophylline concentrations were used to calculate percentage prediction errors defined as %PE=[(predicted conc. - measured conc.)/measured conc.] x 100. A linear regression analysis was also carried out for the observed concentrations and those predicted by each method (PKS vs. CAPCIL). RESULTS: The predicted concentrations indicating persistently over-predicted the observed theophylline serum levels (results expressed as median and interquartile range; %PE for PKS=58.1 [37.1-126.0]; %PE for CAPCIL=34.0 [12.5-93.8]). The regression analysis confirmed the same tendency, showing an intercept significantly different from zero using both PKS and CAPCIL. CONCLUSION: The results suggest a possible interaction between theophylline and auranofin. Both PKS and CAPCIL failed to predict theophylline serum levels based exclusively on population pharmacokinetic parameters. The lower observed concentrations than expected have obvious implications in practice. Periodic theophylline serum determinations are advisable until further studies provide the necessary clarification about the kinetic profile of theophylline in patients taking concomitant steroids and gold salts.

Adult↗

PubMed1998

A New Method for Estimating Model Parameters for Multinomial Data.

A new procedure for estimating the parameters of a scientific model is described, and the method is applied and illustrated for the class of experiments with multinominal data structure. The procedure is referred to as the method of population-parameter mapping, and it has a number of novel and advantageous features. The method is a variation of a standard Bayesian analysis. However, instead of directly developing a posterior distribution for the model parameters, this procedure first characterizes the population proportions for the multinomial cells. Random samples are then drawn from the posterior distribution for these proportions, and these samples are mapped to the parameters of the scientific model. This method leads naturally to a definition of model identifiability, and leads to a direct probability estimate of the coherence of the scientific model. Moreover, the new procedure can circumvent the problem of dealing with computationally difficult integrals that frequently occur with Bayesian analyses of complex multinomial models. The method is illustrated by means of several memory measurement models as well as a signal-detection model. Copyright 1998 Academic Press.

Journal Article↗

PubMed2006

Analysis of rabbit doe longevity using a semiparametric log-Normal animal frailty model with time-dependent covariates.

Data on doe longevity in a rabbit population were analysed using a semiparametric log-Normal animal frailty model. Longevity was defined as the time from the first positive pregnancy test to death or culling due to pathological problems. Does culled for other reasons had right censored records of longevity. The model included time dependent covariates associated with year by season, the interaction between physiological state and the number of young born alive, and between order of positive pregnancy test and physiological state. The model also included an additive genetic effect and a residual in log frailty. Properties of marginal posterior distributions of specific parameters were inferred from a full Bayesian analysis using Gibbs sampling. All of the fully conditional posterior distributions defining a Gibbs sampler were easy to sample from, either directly or using adaptive rejection sampling. The marginal posterior mean estimates of the additive genetic variance and of the residual variance in log frailty were 0.247 and 0.690.

Animals↗

PubMedDate not supplied

MD@: a physician-friendly decision analysis tool.

The cost-effective use of medical resources is increasingly important in justifying strategies for medical diagnosis and management. Although some software is available to help with decision analysis, it can be difficult to use these tools for medical applications. We have developed a prototype package for modeling various medical decision strategies, which can be used with a Macintosh or Windows-based personal computer. The system is graphically based, intuitive, and user-friendly. The user constructs decision trees for comparing alternative strategies for diagnosis and management. Selecting blocks from a library, the user sets mean values for variables such as prevalence, sensitivity, specificity, cost, morbidity, and mortality. The system then generates the probabilities of various pathways, using Bayesian analysis, without requiring the user to enter equations. It displays the best strategy in terms of a particular criterion and, when appropriate, performs sensitivity analysis.

Decision Support Techniques↗

PubMed2007

Protein identification by tandem mass spectrometry and sequence database searching.

The shotgun proteomics strategy, based on digesting proteins into peptides and sequencing them using tandem mass spectrometry (MS/MS), has become widely adopted. The identification of peptides from acquired MS/MS spectra is most often performed using the database search approach. We provide a detailed description of the peptide identification process and review the most commonly used database search programs. The appropriate choice of the search parameters and the sequence database are important for successful application of this method, and we provide general guidelines for carrying out efficient analysis of MS/MS data. We also discuss various reasons why database search tools fail to assign the correct sequence to many MS/MS spectra, and draw attention to the problem of false-positive identifications that can significantly diminish the value of published data. To assist in the evaluation of peptide assignments to MS/MS spectra, we review the scoring schemes implemented in most frequently used database search tools. We also describe statistical approaches and computational tools for validating peptide assignments to MS/MS spectra, including the concept of expectation values, reversed database searching, and the empirical Bayesian analysis of PeptideProphet. Finally, the process of inferring the identities of the sample proteins given the list of peptide identifications is outlined, and the limitations of shotgun proteomics with regard to discrimination between protein isoforms are discussed.

Amino Acid Sequence↗

PubMed2005

Modeling association among demographic parameters in analysis of open population capture-recapture data.

We present a hierarchical extension of the Cormack-Jolly-Seber (CJS) model for open population capture-recapture data. In addition to recaptures of marked animals, we model first captures of animals and losses on capture. The parameter set includes capture probabilities, survival rates, and birth rates. The survival rates and birth rates are treated as a random sample from a bivariate distribution, thus the model explicitly incorporates correlation in these demographic rates. A key feature of the model is that the likelihood function, which includes a CJS model factor, is expressed entirely in terms of identifiable parameters; losses on capture can be factored out of the model. Since the computational complexity of classical likelihood methods is prohibitive, we use Markov chain Monte Carlo in a Bayesian analysis. We describe an efficient candidate-generation scheme for Metropolis-Hastings sampling of CJS models and extensions. The procedure is illustrated using mark-recapture data for the moth Gonodontis bidentata.

Animals↗

PubMed2005

Climate and life-history evolution in evening primroses (Oenothera, Onagraceae): a phylogenetic comparative analysis.

Evolutionary ecologists have long sought to understand the conditions under which perennial (iteroparous) versus annual (semelparous) plant life histories are favored. We evaluated the idea that aridity and variation in the length of droughts should favor the evolution of an annual life history, both by decreasing adult survival and by increasing the potential for high seedling survival via reduced plant cover. We calculated phylogenetically independent contrasts of climate with respect to life history in a clade of winter-establishing evening primroses (sections Anogra and Kleinia; Oenothera; Onagraceae), which includes seven annuals, 12 perennials, and two variable taxa. Climate variables were quantified from long-term records at weather stations near collection localities. To explicitly account for phylogenetic uncertainty, contrasts were calculated on a random sample of phylogenetic trees from the posterior distribution of a Bayesian analysis of DNA sequence data. Statements of association are based on comparing the per-tree mean contrast, which has a null expectation of zero, to a set of per-tree mean contrasts calculated on the same trees, after randomizing the climate data. As predicted, increased annual aridity, increased annual potential evapotranspiration, and decreased annual precipitation were associated with transitions to the annual habit, but these trends were not significantly different from the null pattern. Transitions to the annual habit were not significantly associated with increases in one measure of aridity in summer nor with increased summer drought, but they were associated with significantly increased maximum summer temperatures. In winter, increased aridity and decreased precipitation were significantly associated with transitions to the annual habit. Changes in life history were not significantly associated with changes in the coefficient of variation of precipitation, either on an annual or seasonal (summer vs. winter) basis. Though we cannot attribute causality on the basis of a correlational, historical study, our results are consistent with the idea that increased heat and drought at certain times of the year favor the evolution of the annual habit. Increased heat in summer may cause adult survival to decline, while increased aridity and decreased precipitation in the season of seedling recruitment (winter) may favor a drought-avoiding, short-lived annual strategy. Not all of the predicted patterns were observed: the capability for drought-induced dormancy may preclude change in habit in response to summer drought in our study group.

Base Sequence↗