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PubMed2004

Predicting survival causes after out of hospital cardiac arrest using data mining method.

BACKGROUND: The prognosis of life for patients with heart failure remains poor. By using data mining methods, the purpose of this study was to evaluate the most important criteria for predicting patient survival and to profile patients to estimate their survival chances together with the most appropriate technique for health care. METHODS: Five hundred and thirty three patients who had suffered from cardiac arrest were included in the analysis. We performed classical statistical analysis and data mining analysis using mainly Bayesian networks. RESULTS: The mean age of the 533 patients was 63 (+/- 17) and the sample was composed of 390 (73 %) men and 143 (27 %) women. Cardiac arrest was observed at home for 411 (77 %) patients, in a public place for 62 (12 %) patients and on a public highway for 60 (11 %) patients. The belief network of the variables showed that the probability of remaining alive after heart failure is directly associated to five variables: age, sex, the initial cardiac rhythm, the origin of the heart failure and specialized resuscitation techniques employed. CONCLUSIONS: Data mining methods could help clinicians to predict the survival of patients and then adapt their practices accordingly. This work could be carried out for each medical procedure or medical problem and it would become possible to build a decision tree rapidly with the data of a service or a physician. The comparison between classic analysis and data mining analysis showed us the contribution of the data mining method for sorting variables and quickly conclude on the importance or the impact of the data and variables on the criterion of the study. The main limit of the method is knowledge acquisition and the necessity to gather sufficient data to produce a relevant model.

Bayes Theorem↗

PubMed1997

Meta-analysis for the evaluation of potential surrogate markers.

We describe a meta-analysis approach for the evaluation of a potential surrogate marker. Surrogate markers are useful in helping to identify therapeutic mechanisms of action and disease pathogenesis, and for selecting therapies to take forward from phase II to phase III clinical trials. They have also become increasingly important for regulatory purposes by providing a basis for preliminary approval of drugs pending clinical outcome studies. Methodology for evaluating surrogate markers has focused on determining the difference in the effects of two treatments on clinical outcome in an individual clinical trial, and then estimating the proportion of this difference explained by the treatment's effects on the potential marker. Studies are, however, frequently underpowered or cease before they accumulate sufficient evidence to draw strong conclusions about the value of a potential surrogate marker using this approach, and there are also some technical difficulties with the approach. Consideration of the association between the difference in treatment effects on the clinical outcome and the difference in treatment effects on the potential marker over a range of trials provides an alternative means to evaluate a potential marker. We describe a meta-analysis approach using Bayesian methods to model this association. Importantly, this approach enables one to obtain prediction intervals for the true difference in clinical outcome for a given estimated treatment difference in the effect on the potential marker. We illustrate the methodology by applying it to results from studies of the AIDS Clinical Trials Group to assess the value of CD4 T-lymphocyte cell count as a potential surrogate marker for the treatment effects on the development of AIDS or death.

Anti-HIV Agents↗

PubMed2005

The ITS2 ribosomal DNA of Anopheles beklemishevi and further remarks on the phylogenetic relationships within the Anopheles maculipennis group of species (Diptera: Culicidae).

Anopheles beklemishevi specimens from Russia were analysed by their ITS2 ribosomal DNA sequence to amend and to specify the phylogenetic tree of the Anopheles maculipennis species complex. Surprisingly, with 638 base pairs, the ITS2 regions of all the 34 An beklemishevi specimens examined were considerably longer than those of all their sibling species. Sequence alignment with GenBank derived sequences of the other siblings was only possible in the beginning (for approx. 335 bp) and at the end (for approx. 150 bp) of the PCR-amplified DNA fragment, whereas in the middle, the An beklemishevi DNA sequence found no counterpart in sequences of the other siblings. Closer analysis of this intermediate part suggests a duplicated insertion of about 140 bp that has undergone subsequent mutational changes. Due to this large putative insertion, computerized phylogenetic analysis by the Bayesian inference method locates An beklemishevi in a closer relationship to the nearctic than to the palaearctic sibling species. However, when only ITS2 regions are compared, that have corresponding sequences in the other siblings, An beklemishevi forms a lineage with the palaearctic species although it is still most remotely related. It is hypothesized that during the evolution An beklemishevi separated first from the common ancestor of the palaearctic species, which had presumably made its way from the Nearctic to the Palaearctic.

Animals↗

PubMed1989

A Bayesian methodology for scaling radiation studies from animals to man.

This paper describes a Bayesian methodology for integrating studies in experimental animals and humans to obtain a risk estimate for a radionuclide for which no data or very limited human data are available. The method is quite general and is not limited to radiation studies. In fact, it was first developed for chemical toxicants. The methodology is illustrated using studies with rats, beagles, and humans exposed to isotopes of Ra and Pu. The goal is a quantitative risk estimate for bone cancer in humans exposed to internally deposited Pu. The choice of bone cancer as an end point and of Pu as the source of exposure was made partially because of its inherent interest but also because of issues of data availability and suitability. We performed Poisson regression analyses on 13 of 15 data sets. These analyses form the basis for the unifying method of interpreting the entire ensemble of studies. Each of the studies is summarized by the estimated dose-response slope and its estimated standard error. These summary statistics are combined with other available biological and physical information about species differences, physical and metabolic characteristics of isotopes, disease mechanisms, and the like. This information enters the analysis in the form of prior assumptions about the parameters of the Bayesian model combining the studies. The posterior distribution for the bone cancer rate in man from the Bayesian analysis of the 13 studies is updated with the limited data on Pu in humans. This update gives the final probability density for the bone cancer rate in humans exposed to internally deposited Pu. This density has a median of about three cancers per 100 Gy and has a 95% probability interval from 0.8 to 11 bone cancers per 100 Gy.

Animals↗

PubMed2006

Phylogeography of Indonesian and Sino-Himalayan region bush warblers (Cettia, Aves).

We present a hypothesis for the phylogeny and phylogeography of a group of bush warblers in the genus Cettia, based on parts of the mitochondrial Cytochrome b gene and the nuclear myoglobin intron II (in all approximately 1.7 kb). Ancestral areas were reconstructed by dispersal-vicariance analysis and constrained Bayesian inference. The results suggest that the insular taxa in the Cettia vulcania group are most closely related to Cettia flavolivacea, and originated from a dispersal by an ancestral population in the Himalayas towards the south, to the Sunda region. From this population, a second dispersal along a different route colonized China and northern Vietnam. Hence, the Chinese taxon intricata and Vietnamese oblita, currently allocated to C. flavolivacea, are more closely related to the vulcania group than to the other taxa in the flavolivacea group, and we propose that they be treated as conspecific with C. vulcania, restricting C. flavolivacea to Myanmar and the Himalayas.

Animals↗

PubMed2005

The phylogenetic relationships among non-diplomystid catfishes as inferred from mitochondrial cytochrome b sequences; the search for the ictalurid sister taxon (Otophysi: Siluriformes).

The relationships among families of catfishes are poorly understood and have yet to be the subject of a comprehensive investigation with molecular data. Existing phylogenetic hypotheses are based on morphological data and incompletely resolved. This study analyzed complete sequences of mitochondrial gene cytochrome b for 170 species from 29 of 33 extant families, and focused on the relationships of Ictaluridae to other catfishes. In addition to previous phylogenetic studies, the fossil record, paleogeography, biogeography, and distribution of extant catfish families collectively suggest the location (if extant) of the ictalurid sister taxon to be Northern or Eastern Asia. Of the extant catfishes currently native to this area and included in this analysis, parsimony and Bayesian likelihood analyses recovered Cranoglanis bouderius as the most proximal sister taxon of Ictaluridae. Seemingly, ictalurids and cranoglanidids represent another biogeographic component linking freshwater fishes of North America and eastern Asia, e.g., catostomids and paddlefishes. The results coupled with present-day catfish distributions and inferences from the fossil record collectively suggest the ancestor of Ictaluridae to have invaded freshwaters of North America at the close of the Cretaceous through northeastern Asia and northwestern North America. Other superfamilial nodes supported the results of previous phylogenetic studies of narrower taxonomic scope. Several novel relationships were recovered (including a clade composed of Pimelodidae, Pseudopimelodidae, and Heptapteridae) and these along with sources of systematic error are discussed. A broad sampling of Bagridae permitted an examination of intergeneric relationships within this family and in light of recent morphological and molecular studies.

Animals↗

PubMed2003

Clinical efficacies of antihypertensive drugs.

OBJECTIVE: According to published data, the ability to prevent various hypertension-related events differs between the various antihypertensive drug groups. Although absolute drug effects differ among studies, relative drug effects could be considered constant. We therefore explored the possibility of drawing statistically valid conclusions about the differences in clinical efficacy between various drug groups by doing an overview of published data. DESIGN: We made a meta-analysis with a Bayesian fixed effect model in which we related the drug effects to the effects of placebo drugs. We selected 27 clinical trials from the literature according to specific criteria, including results from studies reporting the effects of the newer drugs when tested against diuretics and beta-blockers, and from studies in which diuretics and beta-blockers had been tested against placebo. We calculated the posterior probability distributions of the relative effects of angiotensin-converting enzyme (ACE) inhibitors vs calcium antagonists with three different endpoints: stroke, coronary disease and heart failure with point estimates of effects and with 95% credibility intervals. As an intermediate step in this procedure we obtained similar information about the effects of the three groups of active drugs, ACE inhibitors, calcium antagonists and diuretics or beta-blockers, tested against placebo. For coronary disease we also tested calcium antagonists against diuretics or beta-blockers. RESULTS: ACE inhibitors and calcium antagonists have an almost identical ability to prevent stroke in hypertensive individuals with a risk ratio (RR) of 1.04. On the other hand, calcium antagonists reduce coronary disease by only 8% relative to placebo. When ACE inhibitors and calcium antagonists are compared with the Bayesian method, the outcome is a 14% difference in favor of the ACE inhibitors to prevent coronary disease, with a credibility interval almost reaching identity. Nor do calcium antagonists do as well as diuretics or beta-blockers in this respect, RR = 1.12 with 95% credibility interval 1.01-1.24. All the tested drug groups have a profound preventive effect on the occurrence of heart failure when given to hypertensive patients, showing reductions of 42-54%. When ACE inhibitors are compared with calcium antagonists RR = 0.79, with a credibility interval 0.65-0.95. CONCLUSION: There is statistically an indisputable difference between ACE inhibitors and calcium antagonists in respect of effects on coronary disease and heart failure when treating hypertensive individuals, ACE inhibitors being more efficacious. There are no differences in the effect on stroke. Moreover, beta-blockers or diuretics are also superior to calcium antagonists in preventing coronary events.

Adrenergic beta-Antagonists↗

PubMed2003

Analysis of the evolutionary relationships of HIV-1 and SIVcpz sequences using bayesian inference: implications for the origin of HIV-1.

The most plausible origin of HIV-1 group M is an SIV lineage currently represented by SIVcpz isolated from the chimpanzee subspecies Pan troglodytes troglodytes. The origin of HIV-1 group O is less clear. Putative recombination between any of the HIV-1 and SIVcpz sequences was tested using bootscanning and Bayesian-scanning plots, as well as a new method using a Bayesian multiple change-point (BMCP) model to infer parental sequences and crossing-over points. We found that in the case of highly divergent sequences, such as HIV-1/SIVcpz, Bayesian scanning and BMCP methods are more appropriate than bootscanning analysis to investigate spatial phylogenetic variation, including estimating the boundaries of the regions with discordant evolutionary relationships and the levels of support of the phylogenetic clusters under study. According to the Bayesian scanning plots and BMCP method, there was strong evidence for discordant phylogenetic clustering throughout the genome: (1) HIV-1 group O clustered with SIVcpzANT/TAN in middle pol, and partial vif/env; (2) SIVcpzGab1 clustered with SIVcpzANT/TAN in 3'pol/vif, and middle env; (3) HIV-1 group O grouped with SIVcpzCamUS and SIVcpzGab1 in p17/p24; (4) HIV-1 group M was more closely related to SIVcpzCamUS in 3'gag/pol and in middle pol, whereas in partial gp120 group M clustered with group O. Conditionally independent phylogenetic analysis inferred by maximum likelihood (ML) and Bayesian methods further confirmed these findings. The discordant phylogenetic relationships between the HIV-1/SIVcpz sequences may have been caused by ancient recombination events, but they are also due, at least in part, to altered rates of evolution between parental SIVcpz lineages.

Animals↗

PubMed2006

Bayesian method for gene detection and mapping, using a case and control design and DNA pooling.

Association mapping studies aim to determine the genetic basis of a trait. A common experimental design uses a sample of unrelated individuals classified into 2 groups, for example cases and controls. If the trait has a complex genetic basis, consisting of many quantitative trait loci (QTLs), each group needs to be large. Each group must be genotyped at marker loci covering the region of interest; for dense coverage of a large candidate region, or a whole-genome scan, the number of markers will be very large. The total amount of genotyping required for such a study is formidable. A laboratory effort efficient technique called DNA pooling could reduce the amount of genotyping required, but the data generated are less informative and require novel methods for efficient analysis. In this paper, a Bayesian statistical analysis of the classic model of McPeek and Strahs is proposed. In contrast to previous work on this model, I assume that data are collected using DNA pooling, so individual genotypes are not directly observed, and also account for experimental errors. A complete analysis can be performed using analytical integration, a propagation algorithm for a hidden Markov model, and quadrature. The method developed here is both statistically and computationally efficient. It allows simultaneous detection and mapping of a QTL, in a large-scale association mapping study, using data from pooled DNA. The method is shown to perform well on data sets simulated under a realistic coalescent-with-recombination model, and is shown to outperform classical single-point methods. The method is illustrated on data consisting of 27 markers in an 880-kb region around the CYP2D6 gene.

Alleles↗

PubMed1991

Thomas: building Bayesian statistical expert systems to aid in clinical decision making.

Knowledge-based system for classical statistical analysis must separate the task of analyzing data from that of using the results of the analysis. In contrast, a Bayesian framework for building biostatistical expert system allows for the integration of the data-analytic and decision-making tasks. The architecture of such a framework entails enabling the system (1) to make its recommendations on decision-analytic grounds; (2) to construct statistical models dynamically; (3) to update a statistical model based on the user's prior beliefs and on data from, the methodological concerns evinced by, the study. This architecture permits the knowledge engineer to represent a variety of types of statistical and domain knowledge. Construction of such systems requires that the knowledge engineer reinterpret traditional statistical concerns, such as by replacing the notion of statistical significance with that of a pragmatic clinical threshold. The clinical user of such a system can interact with the system at a semantic level appropriate to her fund of methodological knowledge, rather than at the level of statistical details. We demonstrate these issues with a prototype system called THOMAS which helps a physician decision maker interpret the results of a published randomized clinical trial.

Artificial Intelligence↗

PubMed2004

The association between late-onset fecal incontinence and obstetric anal sphincter defects.

HYPOTHESIS: Endoanal ultrasonographic results have demonstrated that clinically occult anal sphincter damage during vaginal delivery is common. This may or may not be associated with postpartum fecal incontinence (FI). Bayesian meta-analysis of the literature revealed that at least two thirds of obstetric sphincter disruptions are asymptomatic in the postpartum period. Women with postpartum asymptomatic sphincter damage may be at increased risk for FI with aging compared with those without sphincter injury. DESIGN: Case series. SETTING: Tertiary referral center. PATIENTS: After excluding patients with other possible causes of FI, the histories of 124 consecutive women with late-onset FI after vaginal delivery were analyzed. MAIN OUTCOME MEASURES: Endoanal ultrasonographic findings, pudendal nerve terminal motor latency assessment, and anal manometric results. RESULTS: Eighty-eight women (71%) with a median of 3 vaginal deliveries had sphincter defects on endoanal ultrasonographic results. The mean incontinence score, squeeze and resting pressures, median age at last delivery, and median duration of FI were not significantly different between patients with and without sphincter defects. Pudendal neuropathy was more frequent in patients without sphincter defects (10 [30.3%], left side; 12 [36.4%], right side) than in patients with sphincter defects (12 [14.3%] and 16 [19.3%], respectively), with the difference nearly reaching statistical significance (P =.054 and P =.059, respectively). The median age at onset of FI in patients with a sphincter defect was 61.5 years vs 68.0 years in those without a sphincter defect, which was not statistically significant (P =.08). CONCLUSION: Analysis of the current patient population revealed that 88 women (71%) with late-onset FI after vaginal delivery had an anatomical sphincter defect. Thus, FI related to anal sphincter defects is likely to occur even in an elderly population who had experienced vaginal deliveries earlier in life.

Aged↗

PubMed2006

Estimating transitions between symptom severity states over time in schizophrenia: a Bayesian meta-analytic approach.

We obtain the posterior predictive distribution of transition probabilities between symptom severity states over time for patients with schizophrenia by (i) employing a Bayesian meta-analysis of published clinical trials and observational studies to estimate the posterior distribution of parameters that guide changes in Positive and Negative Syndrome Scale (PANSS) scores over time and under the influence of various drugs and (ii) by propagating the variability from the posterior distributions of the parameters through a micro-simulation model that is formulated based on schizophrenia progression. Results show detailed differences among haloperidol, risperidone and olanzapine in controlling various levels of severities of positive, negative and joint symptoms over time. For example, risperidone seems best in controlling severe positive symptoms while olanzapine is the worst in that during the first quarter of drug treatment; however, olanzapine seems to be best in controlling severe negative symptoms across all four quarters of treatment while haloperidol is the worst in this regard. These details may further serve to better estimate quality of life of patients and aid in resource utilization decisions in treating schizophrenic patients. In addition, consistent estimation of uncertainty in the time-profile parameters also has important implications for the practice of cost-effectiveness analysis and for future resource allocation policies in schizophrenia treatment.

Antipsychotic Agents↗

PubMed2006

Extensive gene flow blurs phylogeographic but not phylogenetic signal in Olea europaea L.

Genetic structure and evolutionary patterns of the wild olive tree (Olea europaea L.) were investigated with AFLP fingerprinting data at three geographic levels: (a) phylogenetic relationships of the six currently recognized subspecies in Eurasia and Africa; (b) lineage identification in subsp. europaea of the Mediterranean basin; and (c) phylogeography in the western Mediterranean. Two statistical approaches (Bayesian inference and analysis of molecular variance) were used to analyse the AFLP fingerprints. To determine the congruency and transferability of results across studies previous RAPD and ISSR data were analysed in a similar manner. Comparisons proved that qualitative results were mostly congruent but quantitative values differed, depending on the method of analysis. Neighbour-Joining analysis of AFLP phenotypes supported current classification of subspecies. At a Mediterranean scale no clear cut phylogeographic pattern was recovered, likely due to extensive gene flow between populations of subsp. europaea. Gene flow estimates calculated with conventional F-statistics showed that reproductive barriers separated neither populations nor lineages of O. europaea. Genetic divergence between eastern and western parts of the Mediterranean basin was observed only when geographical and population information were incorporated into the analyses through hierarchical analysis of molecular variance (AMOVA). Within the western Mediterranean, the highest genetic diversity was found in two regions: on both sides of the Strait of Gibraltar and in the Balearic archipelago. Additionally, long-lasting isolation of the northern-most populations of the Iberian Peninsula appeared to be responsible for a significant divergence.

DNA Fingerprinting↗

PubMed2005

Examination of ancestry and ethnic affiliation using highly informative diallelic DNA markers: application to diverse and admixed populations and implications for clinical epidemiology and forensic medicine.

We and others have identified several hundred ancestry informative markers (AIMs) with large allele frequency differences between different major ancestral groups. For this study, a panel of 199 widely distributed AIMs was used to examine a diverse set of 796 DNA samples including self-identified European Americans, West Africans, East Asians, Amerindians, African Americans, Mexicans, Mexican Americans, Puerto Ricans and South Asians. Analysis using a Bayesian clustering algorithm (STRUCTURE) showed grouping of individuals with similar ethnic identity without any identifier other than the AIMs genotyping and showed admixture proportions that clearly distinguished different individuals of mixed ancestry. Additional analyses showed that, for the majority of samples, the predicted ethnic identity corresponded with the self-identified ethnicity at high probability (P > 0.99). Overall, the study demonstrates that AIMs can provide a useful adjunct to forensic medicine, pharmacogenomics and disease studies in which major ancestry or ethnic affiliation might be linked to specific outcomes.

Algorithms↗

PubMed2026

Parting ways: Pan-Homo divergence revisited.

The timing of divergence between hominins and the bonobo-chimpanzee clade has been at the core of palaeoanthropological debate for over a century. The earliest molecular studies indicated divergence times ranging from 5 Ma to as recently as 1.3 Ma. This study critically reviews the trends of time estimates published between 1967 and 2023, and analyses how these are supported or rejected by the current molecular and fossil records. We compiled 202 divergence estimates and defined three distinct thresholds based on fossil evidence at 4.4 Ma (Australopithecus anamensis and Ardipithecus ramidus), 6.2 Ma (Orrorin tugenensis and Ardipithecus kadabba), and 7.2 Ma (Sahelanthropus tchadensis). We then used these thresholds to filter out molecular estimates that are too young to fit the fossil record. Overall, the data suggests a divergence event within the late Miocene, with each threshold pushing it further back, 8.63-6.38, 10.33-7.81, and 10.95-8.81 Ma, respectively. We use a quadratic regression to demonstrate that estimates have been slowly shifting from ~ 6 Ma to ~ 8.5 Ma over the past 56 years. A Bayesian meta-analysis of genomic estimates filtered by our most consensual threshold (i.e., assuming Australopithecus belongs to Hominini) indicates that the split must have occurred early in the late Miocene, most likely before 7 Ma (~ 99.5% posterior probability) with a pooled effect of 8.69-7.28 Ma. We conclude that, despite an initial bias towards younger estimates, the molecular timing for the last common ancestor (LCA) of Pan-Homo has been progressively approaching the intervals suggested by the current fossil record.

Animals↗

PubMed2002

Multimodality in the superior colliculus: an information theoretic analysis.

The deep superior colliculus (DSC) integrates multisensory input and triggers an orienting movement toward the source of stimulation (target). It would seem reasonable to suppose that input of an additional modality should always increase the amount of information received by a DSC neuron concerning a target. However, of all DSC neurons studied, only about one half in the cat and one-quarter in the monkey were multimodal. The rest received only unimodal input. Multimodal DSC neurons show the properties of multisensory enhancement, in which the neural response to an input of one modality is augmented by input of another modality, and of inverse effectiveness, in which weaker unimodal responses produce a higher percentage enhancement. Previously, we demonstrated that these properties are consistent with the hypothesis that DSC neurons use Bayes' rule to compute the posterior probability that a target is present given their stochastic sensory inputs. Here we use an information theoretic analysis of our Bayesian model to show that input of an additional modality may indeed increase target information, but only if input received from the initial modality does not completely reduce uncertainty concerning the presence of a target. Unimodal DSC neurons may be those whose unimodal input fully reduces target uncertainty and therefore have no need for input of another modality.

Bayes Theorem↗

PubMed2005

Model inference or model selection: discussion of Klugkist, Laudy, and Hoijtink (2005).

I. Klugkist, O. Laudy, and H. Hoijtink (2005) presented a Bayesian approach to analysis of variance models with inequality constraints. Constraints may play 2 distinct roles in data analysis. They may represent prior information that allows more precise inferences regarding parameter values, or they may describe a theory to be judged against the data. In the latter case, the authors emphasized the use of Bayes factors and posterior model probabilities to select the best theory. One difficulty is that interpretation of the posterior model probabilities depends on which other theories are included in the comparison. The posterior distribution of the parameters under an unconstrained model allows one to quantify the support provided by the data for inequality constraints without requiring the model selection framework.

Analysis of Variance↗

PubMed2006

Dealing with gene expression missing data.

Compared evaluation of different methods is presented for estimating missing values in microarray data: weighted K-nearest neighbours imputation (KNNimpute), regression-based methods such as local least squares imputation (LLSimpute) and partial least squares imputation (PLSimpute) and Bayesian principal component analysis (BPCA). The influence in prediction accuracy of some factors, such as methods' parameters, type of data relationships used in the estimation process (i.e. row-wise, column-wise or both), missing rate and pattern and type of experiment [time series (TS), non-time series (NTS) or mixed (MIX) experiments] is elucidated. Improvements based on the iterative use of data (iterative LLS and PLS imputation--ILLSimpute and IPLSimpute), the need to perform initial imputations (modified PLS and Helland PLS imputation--MPLSimpute and HPLSimpute) and the type of relationships employed (KNNarray, LLSarray, HPLSarray and alternating PLS--APLSimpute) are proposed. Overall, it is shown that data set properties (type of experiment, missing rate and pattern) affect the data similarity structure, therefore influencing the methods' performance. LLSimpute and ILLSimpute are preferable in the presence of data with a stronger similarity structure (TS and MIX experiments), whereas PLS-based methods (MPLSimpute, IPLSimpute and APLSimpute) are preferable when estimating NTS missing data.

Algorithms↗