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PubMed2001

Bayesian association mapping for quantitative traits in a mixture of two populations.

We introduce a novel Bayesian approach to estimate and account for population structure simultaneously with association mapping of multiple quantitative trait loci. The method is designed for an analysis of unrelated individuals from a mixture of two populations (no admixture), where the individual population memberships are unknown. In our approach, the population structure is estimated and accounted for by using data on additional "grouping" markers which are assumed to be in Hardy-Weinberg equilibrium within the populations but have different allele frequencies between the populations. We use Bayesian hierarchical modeling and Markov chain Monte Carlo estimation, where we allow both population stratification and genetic heterogeneity. In our model the number of quantitative trait loci and their positions are treated as random variables, and we obtain their posterior distributions. Here we select the candidate and the grouping markers based on results from a preliminary SOLAR analysis.

Bayes Theorem↗

PubMed2005

Fine mapping by linkage and association in nuclear family and case-control designs.

This report summarizes the Genetic Analysis Workshop 14 contributions related to fine-mapping strategies, in which examining smaller regions by association with single-nucleotide polymorphisms (SNPs) can yield savings in genotyping and multiple-testing penalties. The aim of the analyses conducted in Group 7 contributions was to localize disease susceptibility loci from either the simulated or the Collaborative Study on the Genetics of Alcoholism (COGA) data within identified regions of linkage. Among the 10 contributions, most groups analyzed the simulated data, one group analyzed the COGA data only, and one group analyzed both data sets. The research questions included evaluation of new methods of analysis, as well as comparisons among alternative methods, analytic strategies, and study designs. Methods of interest included an algorithm for SNP marker ordering, a locally weighted transmission disequilibrium test statistic, a likelihood-ratio test statistic for family-based association in nuclear families, a robust test statistic for case-control association studies, and Bayesian spatial modeling methods for haplotype clustering and association. Evaluations included comparisons among confidence intervals for loci detected via linkage, effects of multiple testing adjustments and trade-offs between type I error and power, comparisons among haplotype-based (multilocus) and genotype-based (multilocus and single-locus) association analyses, and design of fine-mapping and replication studies. While several promising new approaches were identified, further development and evaluation of methods for multiple testing, regression modeling of association with multiple markers and haplotypes, and combined treatment of linkage and association data are necessary if we are to identify many of the genes that contribute to complex traits.

Alcoholism↗

PubMed2007

An empirical analysis of US and Japanese health insurance using age-period-cohort decomposition.

Aggregate data on household health insurance expenditure in the US and Japan that are classified by period and age are decomposed into age, period, and cohort effects by using the Bayesian cohort models. These models are developed to overcome the identification problem involved in cohort analysis. Despite the differences between the health insurance systems of the two countries, three interesting empirical findings are obtained. First, in both the countries, the age effects are the most influential, and the cohort effects have negligible influence. The latter provides a striking policy implication since the generational imbalance in social security expenditures is widely recognized in developed countries. Second, in both the countries, the period effects show a roughly upward trend. Finally, the age effects exhibit a roughly upward movement for all age groups in the US; however, in Japan, these effects show a downward movement for the 55-59 age group due to the changes in the health insurance system on retirement.

Adult↗

PubMed2003

Multivariate meta-analysis.

Meta-analysis is now a standard statistical tool for assessing the overall strength and interesting features of a relationship, on the basis of multiple independent studies. There is, however, recent acknowledgement of the fact that in many applications responses are rarely uniquely determined. Hence there has been some change of focus from a single response to the analysis of multiple outcomes. In this paper we propose and evaluate three Bayesian multivariate meta-analysis models: two multivariate analogues of the traditional univariate random effects models which make different assumptions about the relationships between studies and estimates, and a multivariate random effects model which is a Bayesian adaptation of the mixed model approach. Our preferred method is then illustrated through an analysis of a new data set on parental smoking and two health outcomes (asthma and lower respiratory disease) in children.

Asthma↗

PubMed2003

Measuring spatial effects in time to event data: a case study using months from angiography to coronary artery bypass graft (CABG).

The application of Bayesian hierarchical models to measure spatial effects in time to event data has not been widely reported. This case study aims to estimate the effect of area of residence on waiting times to coronary artery bypass graft (CABG) and to assess the role of important individual specific covariates (age, sex and disease severity). The data involved all patients with definite coronary artery disease who were referred to one cardiothoracic unit from five contiguous health authorities covering 488 electoral wards (areas). Time to event was the waiting time in months from angiography (diagnosis) to CABG (event). A number of discrete time survival models were fitted to the data. A discrete baseline hazard was estimated by fitting waiting time non-parametrically into the models. Ward was fitted as a spatial effect using a Gaussian Markov random field prior. Individual specific covariates considered were age, sex and number of diseased vessels. The recently proposed DIC criteria was used for comparing models. Results showed a marked spatial effect on time to bypass surgery after including age, sex and disease severity in the model. Notably this spatial effect was not apparent when these covariates were not included in the model. The observed small area spatial variation in time to CABG warrants further investigation.

Bayes Theorem↗

PubMed2005

Intrinsic meta-analysis of contingency tables.

Meta-analysis has a natural formulation as a Bayesian hierarchical model. The main theoretical difficulty is the construction of a sensible relationship between the parameters of the individual statistical experiments and the meta-parameter. Since that prior information on such a relationship is typically not available, we argue that this relationship should be dictated by the structure of the model at hand. We then propose a novel procedure based on intrinsic priors which we fully develop for the case of meta-analysis of 2 x 2 contingency tables. Illustrations on real and artificial tables are given.

Adrenergic beta-Antagonists↗

PubMed2005

Single patient (n-of-1) trials with binary treatment preference.

The use of a fully parametric Bayesian method for analysing single patient trials based on the notion of treatment 'preference' is described. This Bayesian hierarchical modelling approach allows for full parameter uncertainty, use of prior information and the modelling of individual and patient sub-group structures. It provides updated probabilistic results for individual patients, and groups of patients with the same medical condition, as they are sequentially enrolled into individualized trials using the same medication alternatives. Two clinically interpretable criteria for determining a patient's response are detailed and illustrated using data from a previously published paper under two different prior information scenarios.

Amitriptyline↗

PubMed2006

A Bayesian hierarchical approach to multirater correlated ROC analysis.

In a common ROC study design, several readers are asked to rate diagnostics of the same cases processed under different modalities. We describe a Bayesian hierarchical model that facilitates the analysis of this study design by explicitly modelling the three sources of variation inherent to it. In so doing, we achieve substantial reductions in the posterior uncertainty associated with estimates of the differences in areas under the estimated ROC curves and corresponding reductions in the mean squared error (MSE) of these estimates. Based on simulation studies, both the widths of coverage intervals and MSE of estimates of differences in the area under the curves appear to be reduced by a factor that often exceeds five. Thus, our methodology has important implications for increasing the power of analyses based on ROC data collected from an available study population.

Bayes Theorem↗

PubMed1999

Brain segmentation and the generation of cortical surfaces.

This paper describes methods for white matter segmentation in brain images and the generation of cortical surfaces from the segmentations. We have developed a system that allows a user to start with a brain volume, obtained by modalities such as MRI or cryosection, and constructs a complete digital representation of the cortical surface. The methodology consists of three basic components: local parametric modeling and Bayesian segmentation; surface generation and local quadratic coordinate fitting; and surface editing. Segmentations are computed by parametrically fitting known density functions to the histogram of the image using the expectation maximization algorithm [DLR77]. The parametric fits are obtained locally rather than globally over the whole volume to overcome local variations in gray levels. To represent the boundary of the gray and white matter we use triangulated meshes generated using isosurface generation algorithms [GH95]. A complete system of local parametric quadratic charts [JWM+95] is superimposed on the triangulated graph to facilitate smoothing and geodesic curve tracking. Algorithms for surface editing include extraction of the largest closed surface. Results for several macaque brains are presented comparing automated and hand surface generation.

Algorithms↗

PubMed2006

Genetic relatedness and population differentiation of Himalayan hulless barley (Hordeum vulgare L.) landraces inferred with SSRs.

A set of 107 hulless barley (Hordeum vulgare L. subsp. vulgare) landraces originally collected from the highlands of Nepal along the Annapurna and Manaslu Himalaya range were studied for genetic relatedness and population differentiation using simple sequence repeats (SSRs). The 44 genome covering barley SSRs applied in this study revealed a high level of genetic diversity among the landraces (diversity index, DI = 0.536) tested. The genetic similarity (GS) based UPGMA clustering and Bayesian Model-based (MB) structure analysis revealed a complex genetic structure of the landraces. Eight genetically distinct populations were identified, of which seven were further studied for diversity and differentiation. The genetic diversity estimated for all and each population separately revealed a hot spot of genetic diversity at Pisang (DI = 0.559). The populations are fairly differentiated (theta = 0.433, R(ST) = 0.445) accounting for > 40% of the genetic variation among the populations. The pairwise population differentiation test confirmed that many of the geographic populations significantly differ from each other but that the differentiation is independent of the geographic distance (r = 0.224, P > 0.05). The high level of genetic diversity and complex population structure detected in Himalayan hulless barley landraces and the relevance of the findings are discussed.

Alleles↗

PubMed2006

Lean mass plays a gender-specific role in familial resemblance for femoral neck bone mineral density in adult subjects.

INTRODUCTION: Whether the femoral neck bone mineral density (FN BMD) of children may be better predicted from that of their parents when taking into account the anthropometry of the children was assessed in a healthy adult sample consisting of 86 mother-daughter, 32 mother-son, 32 father-daughter, and 23 father-son pairs from 128 families. Heritability for FN BMD, which is considered to be a measurement of general resemblance, was defined as the regression coefficient of the mean of the parents' BMD. Among the anthropometric factors, lean mass was the most strongly associated with FN BMD following the adjustment for age in women (r=0.52, p<0.0001) and men (r=0.25, p=0.02). After adjustment for age, calcium intake, physical activity, and menopause and hormonal replacement therapy if relevant, heritability estimates (h2) for FN BMD were 0.68+/-0.23 [95% credible interval (CI): 0.15-0.99] in father-daughter pairs, 0.40+/-0.17 (95% CI: 0.08-0.74) in mother-daughter pairs, and 0.19+/-0.15 (95% CI: 0.01-0.57) in father-son pairs. Adjustment for lean mass of children increased the h2 for FN BMD in mother-son pairs [from 0.24+/-0.17 (95% CI: 0.01-0.57) to 0.66+/-0.18 (95% CI: 0.26-0.95)]. The present results show that FN BMD is heritable in adult father-daughter pairs (7.2% of a daughter's FN BMD variance was explained by the father's FN BMD) and that taking into account the lean mass of sons might improve the prediction of their FN BMD based on that of their mother's (reduction of sons' FN BMD residual variance by 5.1%). Taking the lean mass of children into account might improve the prediction of their FN BMD by 9.1% in daughters and by 18.1% in sons, irrespective of their parent's FN BMD. These results, obtained using a Bayesian regression model, have to be confirmed in further studies involving a greater number of adult parent-offspring pairs of both genders before extrapolation to clinical practice.

Absorptiometry, Photon↗

PubMed2004

New NIST sediment SRM for inorganic analysis.

NIST maintains a portfolio of more than 1300 standard reference materials (SRM), more than a third of these relating to measurements in the biological and environmental fields. As part of the continuous renewal and replacement efforts, a set of new marine sediments has been recently developed covering organic and inorganic determinations. This paper describes the steps taken in sample preparation, homogeneity assay, and analytical characterization and certification with specific emphasis on SRM 2702 inorganics in marine sediment. Neutron activation analysis showed the SRM to be highly homogeneous, opening the possibility for use with solid sampling techniques. The certificate provides certified mass fraction values for 25 elements, reference values for eight elements, and information values for 11 elements, covering most of the priority pollutants with small uncertainties of only several percent relative. The values were obtained by combining results from different laboratories and techniques using a Bayesian statistical model. An intercomparison carried out in field laboratories with the material before certification illustrates a high commutability of this SRM.

Certification↗

PubMed2005

A pilot study of ondansetron plus metopimazine vs. ondansetron monotherapy in children receiving highly emetogenic chemotherapy: a Bayesian randomized serial N-of-1 trials design.

GOALS OF WORK: Chemotherapy-induced nausea and vomiting is problematic in paediatric brain tumour treatment protocols which often discourage the use of corticosteroids as anti-emetics. The dopamine receptor antagonist, metopimazine, is an effective anti-emetic in combination with ondansetron in adults. The present study was designed to assess its efficacy in children with cancer, a group in which it has not been studied previously. PATIENTS AND METHODS: We conducted a series of randomized, multiple-crossover, double-blind, placebo-controlled N-of-1 trials comparing ondansetron/metopimazine with ondansetron monotherapy in children with brain tumours receiving highly emetogenic therapy and combined the individual results using Bayesian statistical modeling. MAIN RESULTS: Ten of twelve enrolled patients completed at least one chemotherapy cycle on study (median=2.5 cycles, range 1-11). Two patients were unable to complete any cycles, and a further three patients withdrew from the study prior to completing all cycles because of an inability to tolerate the taste of the study drug. Combination therapy increased the proportion of days during which patients had no emesis (overall odds ratio=1.52, 95% credible region=0.32-6.40, probability of odds ratio>1=72%), decreased the number of emetic episodes per day (overall rate ratio=0.67, 95% credible region=0.15-3.14, probability of rate ratio<1=75%) and decreased parents' ratings of their child's distress. The drug was more effective during the delayed chemotherapy phase than the acute phase. No adverse events were attributed to metopimazine. CONCLUSIONS: Based on this pilot study, we believe that the high likelihood that metopimazine is an effective adjunct to ondansetron monotherapy suggests that this combination therapy is worthy of further study in children receiving emetogenic chemotherapy.

Antiemetics↗

PubMed2026

Minimally invasive versus open abdominoperineal resection and the risk of postoperative perineal hernia: a systematic review and meta-analysis.

BACKGROUND: The impact of minimally invasive surgery on the risk of postoperative perineal hernia after abdominoperineal resection (APR) or extralevator abdominoperineal excision (ELAPE) remains uncertain. This study compares perineal hernia rates and perioperative outcomes between minimally invasive and open approaches. METHODS: PubMed, Scopus, Web of Science, and Cochrane Library were searched through June 2026. Pooled odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated using random-effects models. A Bayesian meta-analysis was additionally performed for the primary outcome. RESULTS: Four comparative observational studies involving 763 patients were included; 249 underwent minimally invasive APR/ELAPE, and 514 underwent open APR/ELAPE. Postoperative perineal hernia was significantly more frequent following minimally invasive surgery (OR 4.13; 95% CI 2.24-7.61; p < 0.001). Intraoperative blood loss was significantly lower in the minimally invasive group (MD - 156.5 mL; 95% CI - 298.4 to - 14.5; p = 0.03), as was operative time (MD - 41.7 min; 95% CI - 60.8 to - 22.5; p < 0.01). No significant differences were observed in hospital stay (MD - 2.5 days; 95% CI - 5.4 to 0.4; p = 0.09) or 30-day readmission rates (OR 1.41; 95% CI 0.82-2.42; p = 0.209). Bayesian analysis yielded a posterior mean OR of 4.04 (95% CrI 1.96-8.36), corresponding to a 99.9% posterior probability that minimally invasive surgery increases the risk of postoperative perineal hernia. CONCLUSION: Minimally invasive APR/ELAPE was associated with an increased risk of postoperative perineal hernia compared with the open approach. Strategies to reduce this complication while preserving the benefits of minimally invasive surgery warrant further investigation.

Humans↗

PubMed2006

Recommended initial loading dose of teicoplanin, established by therapeutic drug monitoring, and outcome in terms of optimal trough level.

Teicoplanin has a long serum half-life, and therefore it takes time to reach a steady-state concentration. An initial loading procedure has been recommended for teicoplanin to enable prompt reaching of the optimal serum trough level (10-15 microg/ml). However, the dose of teicoplanin that should be administered to patients with varying renal function levels remains inconclusive. In this study, we monitored the serum concentrations of teicoplanin in patients with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia and compared different teicoplanin serum concentrations and their clinical efficacy, investigating the significance of the mean dose administered during the initial 3 days. The study included 48 patients with MRSA pneumonia. The peak and trough concentrations of teicoplanin were determined utilizing a fluorescence polarization immunoassay and a two-compartment Bayesian population model. Teicoplanin was given at a loading dose of 400 or 800 mg on the first day, followed by maintenance doses of 200 or 400 mg. The mean initial dose (MID) over the first 3 days was calculated as: (loading dose + dose on 2nd day + dose on 3rd day)/3. Patients with an MID of 266.7 mg or less (400 mg for loading, 200 mg over the 2nd and 3rd days) did not have a trough level that exceeded 10 microg/ml at the point before the injection on the 4th day. Even in patients with hemodialysis (HD), an MID of 266.7 mg was not enough to provide a trough level of 10 microg/ml. Patients with an MID than 533.3 mg had significantly elevated trough levels, showing better outcomes. A multiple regression formula for predicting trough level before the fourth day of administration is given as: 0.034 + 0.030 x (MID; mg) - 0.057 x creatinine clearance (Ccr; ml/min). These findings suggest that 800 mg as an initial dose, followed by 400 mg maintenance doses over the following 2 days, makes it possible to safely attain an optimal trough level, even in the patients with HD.

Aged↗

PubMed2006

Inferential backbone assignment for sparse data.

This paper develops an approach to protein backbone NMR assignment that effectively assigns large proteins while using limited sets of triple-resonance experiments. Our approach handles proteins with large fractions of missing data and many ambiguous pairs of pseudoresidues, and provides a statistical assessment of confidence in global and position-specific assignments. The approach is tested on an extensive set of experimental and synthetic data of up to 723 residues, with match tolerances of up to 0.5 ppm for Calpha and Cbeta resonance types. The tests show that the approach is particularly helpful when data contain experimental noise and require large match tolerances. The keys to the approach are an empirical Bayesian probability model that rigorously accounts for uncertainty in the data at all stages in the analysis, and a hybrid stochastic tree-based search algorithm that effectively explores the large space of possible assignments.

Algorithms↗

PubMed1986

The objective interpretation of histopathological data: an application to the ageing of ovine bruises.

Muscle and adipose tissue from a total of 178 experimental bruises inflicted on sheep and aged from 1 to 72 h old were processed for light microscopic examination. Five observed histopathological features of inflammation and repair were scored semiquantitatively on a scale of 1-4 according to their degrees of change from the normal state. These data were evaluated mathematically using a Bayesian probability model designed for the purpose. The model was able to age bruises with an acceptable degree of accuracy only as either 1-20 h or 24-72 h old but within these constraints a degree of confidence in excess of 90% was achieved. The exact performance of the model depended on the nature and number of tissue samples examined but mathematical ageing was superior to interpretative ageing based on personal experience.

Adipose Tissue↗

PubMed1989

Computer-assisted optimization of aminophylline therapy in the emergency department.

The emergency department (ED) is a unique setting for pharmacokinetic-guided drug administration because of the need to rapidly optimize therapy. We compared outcomes in patients receiving intravenous aminophylline according to population-based ED guidelines (group 1) or Bayesian-derived pharmacokinetic estimates (group 2), we determined predictors for admission or discharge in our study group, and we assessed the ability of a Bayesian pharmacokinetic model to estimate theophylline requirements in the ED. The study population was composed of 82 patients (42 males, 40 females) with a mean age of 43 +/- 15.5 years. Fifteen patients were excluded because of protocol violations. Of the 67 cases studied, 30 were assigned to group 1, and 37 were assigned to group 2. Patient demographics, baseline theophylline concentration, and theophylline loading dose did not differ significantly between treatment groups. The aminophylline maintenance infusion was significantly (P less than .001) lower in group 1 (0.4 +/- 0.2 mg/kg/h) than in group 2 (0.6 +/- 0.2 mg/kg/h). Serum theophylline concentrations at one hour post-loading-dose did not differ significantly between treatment groups; however, significant differences were observed at two hours post-load (P less than .002) and four hours post-load (P less than .001). Baseline peak flow rate (PFR) was significantly (P less than .03) higher in group 1 (170 +/- 85 L/min) than in group 2 (132 +/- 62 L/min), but did not differ significantly at any other times throughout the study. The PFR one hour post-load (PFR-1) was the strongest (P less than .003) predictor of outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗