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PubMed2002

Testing for genetic evidence of population expansion and contraction: an empirical analysis of microsatellite DNA variation using a hierarchical Bayesian model.

The role of past climatic change in shaping the distributions of tropical rain forest vertebrates is central to long-standing hypotheses about the legacy of the Quaternary ice ages. One approach to testing such hypotheses is to use genetic data to infer the demographic history of codistributed species. Population genetic theory that relates the structure of allelic genealogies to historical changes in effective population size can be used to detect a past history of demographic expansion or contraction. The fruit bats Cynopterus sphinx and C. brachyotis (Chiroptera: Pteropodidae) exhibit markedly different distribution patterns across the Indomalayan region and therefore represent an exemplary species pair to use for such tests. The purpose of this study was to test alternative hypotheses about historical patterns of demographic expansion and contraction in C. sphinx and C. brachyotis using a coalescent-based analysis of microsatellite variation. Specifically, we used a hierarchical Bayesian model based on Markov chain Monte Carlo simulations to estimate the posterior distribution of genealogical and demographic parameters. The results revealed strong evidence for population contraction in both species. Evidence for a population contraction in C. brachyotis was expected on the basis of biogeographic considerations. However, similar evidence for population contraction in C. sphinx does not support the hypothesis that this species underwent a pronounced range expansion during the late Quaternary. Genetic evidence for population decline may reflect the consequences of habitat destruction on a more recent time scale.

Animals↗

PubMed2001

Bayesian modeling of age-specific survival in nesting studies under Dirichlet priors.

There has been much work done in nest survival analysis using the maximum likelihood (ML) method. The ML method suffers from the instability of numerical calculations when models having a large number of unknown parameters are used. A Bayesian approach of model fitting is developed to estimate age-specific survival rates for nesting studies using a large class of prior distributions. The computation is done by Gibbs sampling. Some latent variables are introduced to simplify the full conditional distributions. The method is illustrated using both a real and a simulated data set. Results indicate that Bayesian analysis provides stable and accurate estimates of nest survival rates.

Age Factors↗

PubMed2006

Bayesian methods for evidence synthesis in cost-effectiveness analysis.

Recently, health systems internationally have begun to use cost-effectiveness research as formal inputs into decisions about which interventions and programmes should be funded from collective resources. This process has raised some important methodological questions for this area of research. This paper considers one set of issues related to the synthesis of effectiveness evidence for use in decision-analytic cost-effectiveness (CE) models, namely the need for the synthesis of all sources of available evidence, although these may not 'fit neatly' into a CE model. Commonly encountered problems include the absence of head-to-head trial evidence comparing all options under comparison, the presence of multiple endpoints from trials and different follow-up periods. Full evidence synthesis for CE analysis also needs to consider treatment effects between patient subpopulations and the use of nonrandomised evidence. Bayesian statistical methods represent a valuable set of analytical tools to utilise indirect evidence and can make a powerful contribution to the decision-analytic approach to CE analysis. This paper provides a worked example and a general overview of these methods with particular emphasis on their use in economic evaluation.

Bayes Theorem↗

PubMed2005

Collateral missing value imputation: a new robust missing value estimation algorithm for microarray data.

MOTIVATION: Microarray data are used in a range of application areas in biology, although often it contains considerable numbers of missing values. These missing values can significantly affect subsequent statistical analysis and machine learning algorithms so there is a strong motivation to estimate these values as accurately as possible before using these algorithms. While many imputation algorithms have been proposed, more robust techniques need to be developed so that further analysis of biological data can be accurately undertaken. In this paper, an innovative missing value imputation algorithm called collateral missing value estimation (CMVE) is presented which uses multiple covariance-based imputation matrices for the final prediction of missing values. The matrices are computed and optimized using least square regression and linear programming methods. RESULTS: The new CMVE algorithm has been compared with existing estimation techniques including Bayesian principal component analysis imputation (BPCA), least square impute (LSImpute) and K-nearest neighbour (KNN). All these methods were rigorously tested to estimate missing values in three separate non-time series (ovarian cancer based) and one time series (yeast sporulation) dataset. Each method was quantitatively analyzed using the normalized root mean square (NRMS) error measure, covering a wide range of randomly introduced missing value probabilities from 0.01 to 0.2. Experiments were also undertaken on the yeast dataset, which comprised 1.7% actual missing values, to test the hypothesis that CMVE performed better not only for randomly occurring but also for a real distribution of missing values. The results confirmed that CMVE consistently demonstrated superior and robust estimation capability of missing values compared with other methods for both series types of data, for the same order of computational complexity. A concise theoretical framework has also been formulated to validate the improved performance of the CMVE algorithm. AVAILABILITY: The CMVE software is available upon request from the authors.

Algorithms↗

PubMed2005

Genetic variation in the sodium-dependent vitamin C transporters, SLC23A1, and SLC23A2 and risk for preterm delivery.

Vitamin C has been the focus of epidemiologic investigation in preterm delivery (<37 weeks' gestation), which is a leading cause of neonatal mortality and birth-related morbidity. There are two sodium-dependent membrane transporters encoded by SLC23A1 and SLC23A2, which have key roles in human vitamin C metabolism and which control dietary uptake, reabsorption, and tissue distribution of vitamin C. Using maternal DNA, the authors evaluated common single-nucleotide polymorphisms (SNPs) in SLC23A1 and SLC23A2 in a nested case-control analysis of the Pregnancy, Infection, and Nutrition Study (1995-2000) cohort. Of the associations observed for both haplotypes in SLC23A1 and individual SNPs in SLC23A2, the most robust finding is with an intron 2 variant in SLC23A2. Heterozygotes and homozygotes for this variant had a 1.7-fold (95% confidence interval: 0.9, 3.3) and a 2.7-fold (95% confidence interval: 1.2, 6.3) elevation in the risk of spontaneous preterm birth, respectively. Semi-Bayesian hierarchical regression analysis, which simultaneously adjusted for multiple SNPs within the same gene, gave comparable results. The authors' findings link genetic variants in the vitamin C transporters to spontaneous preterm birth, which may explain previous dietary associations. If the findings from this study are confirmed, they may serve as the foundation for genetic risk assessment of nutritional pathways in preterm birth.

Adult↗

PubMedDate not supplied

The economic impact of payer policies after the Rx-to-OTC switch of second-generation antihistamines.

OBJECTIVE: As a result of the over-the-counter (OTC) introduction of loratadine, health plans have been struggling to determine the best policy to incorporate this change within their existing drug benefit structure for second-generation antihistamines (SGA). The objective of this study was to examine the economic impact of payer policies in response to the Rx-to-OTC switch of loratadine. STUDY DESIGN: Decision analysis was used to model the budgetary impact and cost-effectiveness of four policies for SGA benefits for the managed care organization (MCO), employer, and Medicaid perspectives separately. PATIENTS AND METHODS: Outcomes included direct medical costs and lost productivity (employers only), discounted, quality-adjusted life-years (QALYs) saved because of amelioration of allergic rhinitis symptoms and avoidance of unintentional injuries associated with the use of first-generation antihistamines (FGA). Bayesian probabilistic sensitivity analysis was conducted using second-order Monte Carlo simulation. RESULTS: Providing limited OTC and second-tier prescription benefits would cost approximately 0.13 dollars and 0.30 dollars compared to third-tier prescription benefits for employers and MCOs, respectively, and would save Medicaid 0.02 dollars per member per month (PMPM). Providing limited coverage for OTC loratadine while retaining second-tier prescription benefits for SGA was the optimal policy for a willingness to pay below 26,200 dollars per QALY for all payers. CONCLUSIONS: Offering second-tier prescription and limited OTC benefits provides greater effectiveness and is not significantly more expensive PMPM than discontinuation. Some of the drug savings from limiting coverage of prescription SGA may be attenuated by the cost of lost productivity and direct medical expenditures due to unintentional injuries associated with increased FGA use in addition to the increased cost of therapeutic substitutes.

Bayes Theorem↗

PubMed1997

A Bayesian approach to validating STR multiplex databases for use in forensic casework.

A previous paper in this journal has described the conventional statistical analysis of three databases (Caucasian, Afro-Caribbean and Asians from the Indian subcontinent) where individuals are typed at six short tandem repeat (STR) loci. This paper presents a Bayesian analysis of the same data and the approach is centred on the concept of estimating coancestry coefficients from mixed databases. Posterior distributions for the three databases are presented and the discussed and the consequences of implementing bootstrap estimation procedures are also shown.

Bayes Theorem↗

PubMed2006

Bayesian evidence synthesis to extrapolate survival estimates in cost-effectiveness studies.

This paper is concerned with survival extrapolation that represents an integral part of cost-effectiveness analysis. In the absence of long-term survival estimates from randomized clinical trials or meta-analysis we show how age-sex matched U.K. population data can additionally be used to estimate survival patterns. We adopt a Bayesian approach and we synthesize evidence from different sources such as patient registries, U.K. population statistics and meta-analyses. We also present methodology for Bayesian analysis of the additive hazards model and we show how to apply the techniques using freely available software. The methods are illustrated using data from a cohort of cardiac arrhythmia patients.

Aged↗

PubMed1981

Operability of nuclear instruments for medical use in developing countries. A decision-analytic approach.

Nuclear technology in diagnostic medicine has become a world-wide phenomenon. One of the problems encountered in implementing this technology in developing countries is predicting the operability of nuclear instruments under local conditions of maintenance and use. Our approach to this problem employs an analytic method often applied in medical decision making, and which can be incorporated into schemes for evaluating the total diagnostic process which utilizes nuclear technology. A recent survey of nine types of nuclear instruments in medical use in eight countries in Southeast Asia provided comprehensive information on the application and maintenance of these instruments, as well as a detailed record of actual operability and use of these instruments over a six-month period. A multivariate statistical analysis for predicting the operability of these instruments was carried out with some of the survey data. Responses to a set of 14 potentially important attributes of instrument use and maintenance obtained from the survey data were used to estimate the posterior probabilities of an instrument being inoperable for more than a given total number of hours in the six-month period during which operability was required. The posterior probabilities were determined by means of both Bayesian and discriminant analysis and summarized in the form of receiver operating characteristic (ROC) curves. Among a number of possible interpretations of the results, the analysis suggests that attributes generally involving installation, documentation, environment, and personnel training appear to be particularly important in predicting the operability of the instruments surveyed.

Decision Making↗

PubMed1987

Effect of using warfarin plasma concentrations in Bayesian forecasting of prothrombin-time response.

The predictive performance of a Bayesian computer program using prothrombin-time (PT) response data with and without warfarin plasma concentrations to forecast patients' PTs at the time of hospital discharge was evaluated. A log-linear pharmacokinetic-pharmacodynamic model was used to describe and predict warfarin dose response in patients recently started on warfarin sodium. Individual patients' pharmacodynamic variables relating warfarin concentration to clotting-factor synthesis were obtained by Bayesian nonlinear regression analysis. Pharmacokinetic values for warfarin clearance and volume of distribution were either calculated using nonlinear regression from measured plasma warfarin concentrations or estimated based on literature-derived population regression equations. Percent mean absolute prediction error (precision) and prediction error (bias) for PT predictions were compared among and between analysis methods that used only literature data to estimate PT response and methods that used zero to five PTs with or without warfarin plasma concentrations. Eleven women and eight men completed the study. Predictions after four days of warfarin therapy using PT measurements beginning after either the first or third warfarin dose were clinically useful regardless of whether warfarin concentrations were used in the predictions. Predictions using fewer than four PT measurements were imprecise and biased. The Bayesian method in this study provided good predictions of PTs immediately before hospital discharge based on warfarin dosing and PT response after either four or five days of therapy. The use of warfarin plasma concentrations in the pharmacokinetic-pharmacodynamic model used here appears unwarranted.

Adolescent↗

PubMed2006

Spatiotemporal noise covariance estimation from limited empirical magnetoencephalographic data.

The performance of parametric magnetoencephalography (MEG) and electroencephalography (EEG) source localization approaches can be degraded by the use of poor background noise covariance estimates. In general, estimation of the noise covariance for spatiotemporal analysis is difficult mainly due to the limited noise information available. Furthermore, its estimation requires a large amount of storage and a one-time but very large (and sometimes intractable) calculation or its inverse. To overcome these difficulties, noise covariance models consisting of one pair or a sum of multi-pairs of Kronecker products of spatial covariance and temporal covariance have been proposed. However, these approaches cannot be applied when the noise information is very limited, i.e., the amount of noise information is less than the degrees of freedom of the noise covariance models. A common example of this is when only averaged noise data are available for a limited prestimulus region (typically at most a few hundred milliseconds duration). For such cases, a diagonal spatiotemporal noise covariance model consisting of sensor variances with no spatial or temporal correlation has been the common choice for spatiotemporal analysis. In this work, we propose a different noise covariance model which consists of diagonal spatial noise covariance and Toeplitz temporal noise covariance. It can easily be estimated from limited noise information, and no time-consuming optimization and data-processing are required. Thus, it can be used as an alternative choice when one-pair or multi-pair noise covariance models cannot be estimated due to lack of noise information. To verify its capability we used Bayesian inference dipole analysis and a number of simulated and empirical datasets. We compared this covariance model with other existing covariance models such as conventional diagonal covariance, one-pair and multi-pair noise covariance models, when noise information is sufficient to estimate them. We found that our proposed noise covariance model yields better localization performance than a diagonal noise covariance, while it performs slightly worse than one-pair or multi-pair noise covariance models - although these require much more noise information. Finally, we present some localization results on median nerve stimulus empirical MEG data for our proposed noise covariance model.

Algorithms↗

PubMed1990

A Bayesian method for synthesizing evidence. The Confidence Profile Method.

This article describes a collection of meta-analysis techniques based on Bayesian statistics for interpreting, adjusting, and combining evidence to estimate parameters and outcomes important to the assessment of health technologies. The result of an analysis by the Confidence Profile Method is a joint posterior probability distribution for the parameters of interest, from which marginal distributions for any particular parameter can be calculated. The method can be used to analyze problems involving a variety of types of outcomes, a variety of measures of effect, and a variety of experimental designs. This article presents the elements necessary for analysis, including prior distributions, likelihood functions, and specific models for experimental designs that include adjustment for biases.

Bayes Theorem↗

PubMed2004

A molecular supermatrix of the rabbits and hares (Leporidae) allows for the identification of five intercontinental exchanges during the Miocene.

The hares and rabbits belonging to the family Leporidae have a nearly worldwide distribution and approximately 72% of the genera have geographically restricted distributions. Despite several attempts using morphological, cytogenetic, and mitochondrial DNA evidence, a robust phylogeny for the Leporidae remains elusive. To provide phylogenetic resolution within this group, a molecular supermatrix was constructed for 27 taxa representing all 11 leporid genera. Five nuclear (SPTBN1, PRKCI, THY, TG, and MGF) and two mitochondrial (cytochrome b and 12S rRNA) gene fragments were analyzed singly and in combination using parsimony, maximum likelihood, and Bayesian inference. The analysis of each gene fragment separately as well as the combined mtDNA data almost invariably failed to provide strong statistical support for intergeneric relationships. In contrast, the combined nuclear DNA topology based on 3601 characters greatly increased phylogenetic resolution among leporid genera, as was evidenced by the number of topologies in the 95% confidence interval and the number of significantly supported nodes. The final molecular supermatrix contained 5483 genetic characters and analysis thereof consistently recovered the same topology across a range of six arbitrarily chosen model specifications. Twelve unique insertion-deletions were scored and all could be mapped to the tree to provide additional support without introducing any homoplasy. Dispersal-vicariance analyses suggest that the most parsimonious solution explaining the current geographic distribution of the group involves an Asian or North American origin for the Leporids followed by at least nine dispersals and five vicariance events. Of these dispersals, at least three intercontinental exchanges occurred between North America and Asia via the Bering Strait and an additional three independent dispersals into Africa could be identified. A relaxed Bayesian molecular clock applied to the seven loci used in this study indicated that most of the intercontinental exchanges occurred between 14 and 9 million years ago and this period is broadly coincidental with the onset of major Antarctic expansions causing land bridges to be exposed.

Animals↗

PubMed1992

Anesthetic techniques during surgical repair of femoral neck fractures. A meta-analysis.

Fracture of the hip typically occurs in older women. These patients usually have serious accompanying chronic illnesses. There is a difference of opinion as to the choice of regional versus general anesthesia for surgery in these patients. This meta-analysis compared survival of patients with traumatic femoral neck fractures undergoing operative repair during regional or general anesthesia. The data sources were articles comparing regional and general anesthesia from peer reviewed journals. Thirteen randomized controlled trials were found. Besides 1-month mortality, variables used were estimated operative blood loss and the incidence of deep venous thrombosis. For dichotomous outcomes, two effect measures were calculated: the difference in probabilities and the odds ratio. For blood loss, a continuous variable, the effect measure was the mean difference in blood loss. A random-effects Bayesian meta-analysis was used to combine study data, estimate parameters and create 95% confidence intervals. Only the incidence of deep venous thrombosis was clearly greater for patients receiving general anesthesia, being 31 percentage points higher than for patients receiving regional anesthesia. By the odds ratio, deep venous thrombosis was almost four times more likely following general anesthesia. There was no difference in estimated operative blood loss. By probability difference, mortality was a non-significant 2.7 percentage points less following regional anesthesia. By odds ratio effect measure, death was 1.5 times more likely following general anesthesia, but the lower bound of the 95% confidence interval was close to 1. Meta-analysis does not allow a conclusion that important differences in mortality exist between regional and general anesthesia for traumatic hip fracture surgery.

Aged↗

PubMed2002

Postmenopausal estrogen replacement and risk for venous thromboembolism: a systematic review and meta-analysis for the U.S. Preventive Services Task Force.

BACKGROUND: Postmenopausal estrogen replacement is widely used in the United States but poses important health risks. PURPOSE: To assess the risk for venous thromboembolism with postmenopausal estrogen replacement by using literature review and meta-analysis. DATA SOURCES: All relevant English-language studies identified in searches of the MEDLINE (1966 to December 2000), HealthSTAR (1975 to December 2000), and Cochrane Library databases, and references lists of key articles. STUDY SELECTION: All published studies of postmenopausal estrogen replacement reporting venous thromboembolism as an outcome or adverse event. DATA EXTRACTION: 12 studies of estrogen were identified (3 randomized, controlled trials; 8 case-control studies; and 1 cohort study). Data were extracted on participants, interventions, event rates, and confounders. Two reviewers independently rated study quality on the basis of established criteria. DATA SYNTHESIS: A Bayesian meta-analysis was conducted. When data from all studies were pooled, current estrogen use was associated with an increased risk for venous thromboembolism (relative risk, 2.14 [95% credible interval, 1.64 to 2.81]). Estimates did not significantly change when studies were pooled according to study design, quality score, or whether participants had preexisting coronary artery disease. The absolute rate increase was 1.5 venous thromboembolic events per 10 000 women in 1 year. Six case-control studies that reported risk according to duration of use found that risk was highest in the first year of use (relative risk, 3.49 [credible interval, 2.33 to 5.59]). CONCLUSION: Postmenopausal estrogen replacement is associated with an increased risk for venous thromboembolism, and this risk may be highest in the first year of use.

Bayes Theorem↗

PubMed2003

Limited sampling strategies using Bayesian estimation or multilinear regression for cyclosporin AUC(0-12) monitoring in cardiac transplant recipients over the first year post-transplantation.

OBJECTIVE: The aim of this study was to develop routinely applicable limited sampling strategies for assessing cyclosporin (CsA) AUC(0-12 h), and possibly other exposure indices such as AUC(0-4 h) and C(max), in heart transplant patients over the first year post-transplantation. METHODS: First, the individual pharmacokinetics (PKs) of 14 adult heart-transplant patients receiving Neoral were assessed at three post-transplantation periods, at the end of the first week (W1), the third month (M3) and the first year (Y1). To fit blood concentrations, a PK model specially developed for oral CsA was applied. Second, two statistical methods were compared for AUC(0-12 h) estimation using a limited sampling strategy (maximum of three blood samples): multiple regression analysis (MR) and Bayesian estimation (BE). RESULTS: No significant difference was observed between the individual PK parameters at M3 and Y1, so population modelling was performed taking as a whole the concentration data collected at M3 and Y1. On the contrary, a significant difference ( P<0.05) was found for the C2/dose ratio between W1 and M3 and between W1 and Y1 (mean+/-SD =5.47+/-2.33; 7.78+/-1.05; 6.98+/-2.17 ml(-1 )for W1, M3 and Y1, respectively). Also, C(max)/dose and A were found significantly lower at W1 than at M3 ( P<0.01 and P<0.005, respectively), while lambda(1) was significantly higher at W1 than at both M3 and Y1 ( P<0.01). Using three sampling times (t0 h, t1 h and t3 h), BE allowed an accurate prediction of AUC(0-12 h) (mean bias =3.06+/-12.16%; +1.50+/-1.61%; and -0.20+/-11.42% at W1, M3 and Y1, respectively), AUC(0-4 h )and C(max). MR led to satisfactory estimation of AUC(0-12 h) using only two blood samples collected 2 h and 6 h post-dose (R=0.956-0.993; bias =-5.22 to +4.41; precision =6.38 to 9.90%), but this method is unable to estimate any other exposure index and requires strict respect of sampling times, contrary to BE. CONCLUSION: Neoral monitoring based on full or abbreviated AUC is possible using BE or MR in heart transplant patients over the first year post-transplantation. BE provides a good description of the individual PK profiles and thus might be useful not only in case of potential discrepancies between C2 and clinical findings, but also for clinical trials aimed at finding optimum PK monitoring in heart recipients.

Area Under Curve↗

PubMedDate not supplied

Identification of genes associated with ovarian cancer metastasis using microarray expression analysis.

Although the transition from early- to advanced-stage ovarian cancer is a critical determinant of survival, little is known about the molecular underpinnings of ovarian metastasis. We hypothesize that microarray analysis of global gene expression patterns in primary ovarian cancer and metastatic omental implants can identify genes that underlie the metastatic process in epithelial ovarian cancer. We utilized Affymetrix U95Av2 microarrays to characterize the molecular alterations that underlie omental metastasis from 47 epithelial ovarian cancer samples collected from multiple sites in 20 patients undergoing primary surgical cytoreduction for advanced-stage (IIIC/IV) serous ovarian cancer. Fifty-six genes demonstrated differential expression between ovarian and omental samples (P < 0.01), and twenty of these 56 differentially expressed genes have previously been implicated in metastasis, cell motility, or cytoskeletal function. Ten of the 56 genes are involved in p53 gene pathways. A Bayesian statistical tree analysis was used to identify a 27-gene expression pattern that could accurately predict the site of tumor (ovary versus omentum). This predictive model was evaluated using an external data set. Nine of the 27 predictive genes have previously been shown to be involved in oncogenesis and/or metastasis, and 10/27 genes have been implicated in p53 pathways. Microarray findings were validated by real-time quantitative PCR. We conclude that gene expression patterns that distinguish omental metastasis from primary epithelial ovarian cancer can be identified and that many of the genes have functions that are biologically consistent with a role in oncogenesis, metastasis, and p53 gene networks.

Bayes Theorem↗

PubMed2003

Chaotic-time-series reconstruction by the Bayesian paradigm: right results by wrong methods.

Recently, papers have appeared that champion the Bayesian approach to the analysis of experimental data. From reading these papers, the physicist could be forgiven for believing that Bayesian methods reveal deep truths about physical systems and are the correct paradigm for the analysis of all experimental data. This paper makes a contrary argument and is deliberately provocative. It is argued that the Bayesian approach to reconstruction of chaotic time series is fundamentally flawed, and the apparent successes result not from any degree of correctness of the paradigm, but by an accidental and unintended property of an algorithm. We also argue that (non-Bayesian) shadowing techniques provide all the information the erroneous Bayesian methods obtain, but much more efficiently, and also provide a wealth of additional useful information.

Journal Article↗