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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↗

PubMed2026

Precision targeting of teacher burnout using network-informed ecological momentary interventions.

Teacher well-being affects classroom functioning and workforce stability, yet generic digital programs rarely use person-specific affect dynamics to select support. This cluster-randomised trial evaluated whether micro-interventions selected from high expected influence (EI) nodes in teachers' contemporaneous affect networks produced larger changes in burnout-related EI and everyday happiness than content-matched random allocation. The objectives were to estimate allocation effects on changes in estimated network summaries and happiness, evaluate network change as a statistical mediator, examine personality moderation, and benchmark simpler allocation rules. A two-arm cluster randomised platform trial was conducted in 84 public schools across four urban districts in H Province. After a 14 day baseline of ecological momentary assessment (EMA), person specific partial correlation networks were estimated for happiness, exhaustion, detachment, efficacy and rumination. An optimisation engine prioritised three brief micro-intervention types per teacher according to baseline EI, while the active control received the same library without network information. EMA continued for 8 weeks; Bayesian multilevel models, permutation-based mediation, and benchmarking analyses were applied. EI-based targeting produced larger reductions in the composite EI-change index than active control (mean difference 0.11, 95% credible interval 0.08 to 0.14) and higher week 7 EMA happiness (4.4 points on a 0 to 100 scale, 95% credible interval 2.7 to 6.0), with a positive arm by week slope difference of 0.62 points per week (95% credible interval 0.39 to 0.85). Model-based mediation estimates were consistent with approximately one half of the happiness difference being statistically associated with change in the composite EI-change index (average conditional mediation estimate 3.5 points, 95% credible interval 2.0 to 5.2). Benchmarking showed smaller gains under severity, threshold, or group-level centrality rules. Effects were stronger among teachers higher in conscientiousness. The findings indicate that integrating EMA, network modelling, and EI-driven optimisation yields measurable gains beyond content-matched exposure, providing a proof of concept for district-scale precision mental health that requires prospective implementation testing. Replication in additional regions, expanded node sets, and longer follow up are warranted to assess durability and generalisability.

Female↗

PubMed1996

Choroid plexus cysts and trisomy 18: risk modification based on maternal age and multiple-marker screening.

Choroid plexus cysts are more common in fetuses with chromosomal aneuploidies, particularly trisomy 18. Although it is accepted that the risk of karyotypic abnormality justifies amniocentesis when associated abnormalities are present, disagreement continues as to the risk of trisomy 18 in a fetus with an isolated choroid plexus cyst. We propose consideration of maternal age and multiple-marker screening for chromosomal aneuploidy in the assessment of risk. Bayesian statistical modeling was used to calculate the risk of trisomy 18 from age-related risk figures for trisomy 18 and the incidence of isolated choroid plexus cysts in fetuses with trisomy 18. The risk was further modified on the basis of the ability of multiple-marker screening to detect fetuses with trisomy 18. From risk estimates calculated across maternal ages 20 to 45 years, the risk of trisomy 18 does not approach that of amniocentesis until a maternal age of > or = 37 years. Therefore in the presence of an isolated choroid plexus cyst and normal multiple-marker screen results amniocentesis is justified only in the patient with advanced maternal age.

Adult↗

PubMed1996

The CYP2D6 genotype predicts the oral clearance of the neuroleptic agents perphenazine and zuclopenthixol.

BACKGROUND: Most antidepressant and neuroleptic agents are metabolized by the polymorphic cytochrome P450 enzyme CYP2D6. This study evaluates the importance of the CYP2D6 genotype for the disposition of the neuroleptic agents perphenazine and zuclopenthixol. METHODS: Patients treated with neuroleptic agents (n = 36) were studied prospectively with regard to CYP2D6 genotype and neuroleptic plasma concentration during oral treatment. Because no patient provided enough samples for individual kinetic modeling, a bayesian approach was used for determination of the clearance. Population kinetic parameters for this procedure were collected from retrospective therapeutic drug monitoring data (n = 113) by use of a nonparametric approach. RESULTS: The CYP2D6 genotype significantly predicted the oral clearance of perphenazine and zuclopenthixol (p < 0.01 by multiple regression). The difference in clearance between homozygous extensive metabolizers and poor metabolizers was threefold for perphenazine and twofold for zuclopenthixol. CONCLUSION: The results show that the genotype for CYP2D6 is closely related to the oral clearances of perphenazine and zuclopenthixol. If this finding can be confirmed in a larger population, genotyping may become an important tool for the dosing of these two neuroleptic agents.

Administration, Oral↗

PubMed1998

Reducing the incidence of epileptic seizures in the Belgian Tervuren through selection.

There is growing evidence that idiopathic epilepsy in the Belgium Tervuren has a genetic foundation. Reducing the incidence of this disorder, which may afflict as much as 17% of the breed, will rely upon the wise selection of parents. Seizure data on 997 dogs from the American Belgian Tervuren Club were collected through questionnaires in which animals were classified into one of four mutually exclusive categories: 1) no seizures observed, 2) one seizure observed, 3) two to five seizures, and 4) more than five seizures. The analysis of this ordered data made use of a threshold model of Bayesian inference. Integration of posterior densities was accomplished through Gibbs sampling. Through this analysis we are able to predict that the offspring of the mating of two non-epileptic dogs has a probability of 0.99 of never suffering from a seizure. The offspring of the mating of two dogs who have each had 1 seizure has a predicted probability 0.58 of never suffering from a seizure. Prevention of this disease is best prescribed through the selection of non-epileptic dogs as parents of future generations.

Animals↗

PubMed1993

[Computer-assisted intravenous anesthesia: value, method and use].

Total intravenous anaesthesia (TIVA) is becoming increasingly popular among anaesthetists. It has several advantages, namely each component of the anaesthetic protocol can be independently controlled, and the operating room remains unpolluted with nitrous oxide or volatile anaesthetic agents. TIVA aims to maintain a constant blood concentration of each anaesthetic agent. This means that infusion rates need to be repeatedly altered. A computer calculates theoretical blood concentrations of agent according to a pharmacokinetic model, and drives an infusion device. Only a few programmes have been developed by research teams. No commercial device is available as yet. However, there are several syringe pumps and volumetric pumps which are accurate enough for use in TIVA and which may be controlled by computer. Clinical studies have shown the benefits of TIVA: greater haemodynamic stability, decreased drug consumption, more rapid recovery, and a lesser need for postoperative ventilatory support. The most appropriate agents are propofol and etomidate as hypnotics, alfentanil and sufentanil for opioids, vecuronium and atracurium as muscle relaxants. Etomidate is not recommended for prolonged infusions, because of the risk of adrenocortical suppression. TIVA seems to be attractive for neurosurgery, thoracic surgery, day case surgery, endoscopic procedures, and anaesthesia in remote locations. Unfortunately, it is an expensive technique. Moreover, there is considerable interpatient variability of the drug concentration required for a same clinical effect. Two methods are proposed to decrease this variability: population pharmacokinetic models and Bayesian forecasting. Closed loop systems are still research tools. It is concluded that computer-driven anaesthesia is the equivalent to the vaporizer for volatile agents. However, further clinical studies are needed to determine whether the advantages of this technique outweigh its disadvantages.

Analgesics, Opioid↗

PubMed2000

HIV testing and retesting for men and women in Switzerland.

This study was conducted to describe voluntary HIV testing in the general population in Switzerland and to estimate yearly HIV test incidence. In 1994, a representative telephone survey of individuals aged 17 to 45 years obtained self-reported information on HIV testing. In addition to describing cumulative HIV test incidence, yearly HIV test incidence over time was estimated by a Bayesian hurdle model allowing for the plausible scenario of test consumption differing between first test and subsequent retests. Overall, 33% of the Swiss population (age 17 to 45 years) has been tested at some time for HIV on a voluntary basis (30% men, 36% women). For the time period 1990-1994, the result showed for 35-year-old individuals with supposedly low risk behavior, that 1) annual test incidence (first test or retest) showed a greater increase for men (4.2 to 5.9%) than for women (5.0 to 6.0%); 2) annual first test incidence increased moderately and differed for men and women (2.9 to 3.4% for men, 4.6 to 5.2% for women), and 3) annual retest incidence was twice as high for men (17.6%) as for women (8.6%). In conclusion, a substantial part of the Swiss population has been tested at some stage for HIV on a voluntary basis, and differences exist for testing and retesting between men and women.

Adolescent↗

PubMed2000

On Bayesian inference for proportional hazards models using noninformative priors.

In this article, we investigate the properties of the posterior distribution under the uniform improper prior for two commonly used proportional hazards models; the Weibull regression model and the extreme value regression model. We allow the observations to be right censored. We obtain sufficient conditions for the existence of the posterior moment generating function of the regression coefficients. A dataset involving a lung cancer clinical trial and a simulation are presented to illustrate our results.

Bayes Theorem↗

PubMed2026

Pneumococcal population structure influences the effects of air pollution on invasive disease risk in South Africa.

Streptococcus pneumoniae is highly diverse, comprising over 100 serotypes and hundreds of genomic lineages amid widespread vaccination. While it can cause invasive pneumococcal disease (IPD) which exhibits pronounced seasonal spikes, the interplay between pneumococcal diversity and environmental drivers remains unexplored. Here we analysed 59,017 IPD cases over 19 years from South Africa, incorporating 4,350 genome-sequenced isolates, using Bayesian spatiotemporal models to link environmental exposure and pneumococcal diversity. Cumulatively, across an 8-week period, moderate relative humidity (33-49%) and cold minimum temperatures (4-10 °C) increased IPD risk by 5% and 4%, respectively. Conversely, warm maximum temperatures (27-38 °C) were associated with up to a 10% increased risk within a week of exposure. There was a positive association between air pollution (PM2.5) and IPD, although it varied by age, disease presentation, and most notably serotype and lineage. Specifically, the lag time between PM2.5 exposure and disease onset varied by serotype, with only serotypes 4, 8 and 23F conferring an immediate IPD risk. High prevalence of GPSC21 lineage (serotype 19F) also modified the pollution response, shifting the lag structure to produce immediate risk of disease following high PM2.5 exposure. Our results demonstrate that pneumococcal population structure shapes air quality risk which in turn can shape the fitness landscape of microbial populations. Integration of these data may inform public health policy.

Journal Article↗

PubMed2025

Limited contributions of bacteria and fungi to coral nutrition revealed by amino acid δ13C analysis.

Corals often form reef ecosystems that support diverse marine life, but they are sensitive to environmental fluctuations that can affect their nutrient acquisition. While coral-associated microbes (e.g., Symbiodiniaceae, bacteria and fungi) may supplement nutrients to coral hosts via metabolite translocation and nutrient recycling, the extent to which these microbial partners contribute to coral autotrophy or heterotrophy remains unclear. Here, we seasonally measure the carbon isotopes of amino acids (δ13CAA) in reef-building coral Pocillopora damicornis and its nutrient sources (e.g., Symbiodiniaceae and particulate organic matter). Regional Bayesian mixing models show that P. damicornis increased autotrophy (from 67.1 to 80.5%), but decreased particulate feeding (from 32.9 to 19.5%) from the cool season to the warm season. Stable essential δ13CAA values (valine, leucine and isoleucine) suggest limited seasonal changes in microbial contributions. Linear discriminant analysis, which combines current and published data from basal organisms (e.g., bacteria and fungi) to coral consumers, also reveals limited bacterial and fungal contributions to coral nutrition. Thus, we advocate that coral nutrition is primarily determined by Symbiodiniaceae translocation and particulate feeding. As these nutritional pathways are highly subject to environmental fluctuations, corals lacking trophic flexibility may suffer more from malnutrition and even population decline under global environmental change.

Anthozoa↗

PubMed2025

Detection of cell-type-specific differentially methylated regions in epigenome-wide association studies.

MOTIVATION: DNA methylation at cytosine-phosphate-guanine (CpG) sites is one of the most important epigenetic markers. Therefore, epidemiologists are interested in investigating DNA methylation in large cohorts through epigenome-wide association studies (EWAS). However, the observed EWAS data are bulk data with signals aggregated from distinct cell types. Deconvolution of cell-type-specific signals from EWAS data is challenging because phenotypes can affect both cell-type proportions and cell-type-specific methylation levels. Recently, there has been active research on detecting cell-type-specific risk CpG sites for EWAS data. However, existing methods all assume that the methylation levels of different CpG sites are independent and perform association detection for each CpG site separately. Although these methods significantly improve the detection at the aggregated-level-identifying a CpG site as a risk CpG site as long as it is associated with the phenotype in any cell type, they have low power in detecting cell-type-specific associations for EWAS with typical sample sizes. RESULTS: Here, we develop a new method, Fine-scale inference for Differentially Methylated Regions (FineDMR), to borrow strengths of nearby CpG sites to improve the cell-type-specific association detection. Via a Bayesian hierarchical model built upon Gaussian process functional regression, FineDMR takes advantage of the spatial dependencies between CpG sites. FineDMR can provide cell-type-specific association detection as well as output subject-specific and cell-type-specific methylation profiles for each subject. Simulation studies and real data analysis show that FineDMR substantially improves the power in detecting cell-type-specific associations for EWAS data. AVAILABILITY AND IMPLEMENTATION: FineDMR is freely available at https://github.com/JiaRuofan/Detection-of-Cell-type-specific-DMRs-in-EWAS.

DNA Methylation↗

PubMed2025

Bayesian estimation of allele-specific expression in the presence of phasing uncertainty.

MOTIVATION: Allele-specific expression (ASE) analyses aim to detect imbalanced expression of maternal versus paternal copies of an autosomal gene. Such allelic imbalance can result from a variety of cis-acting causes, including disruptive mutations within one copy of a gene that impact the stability of transcripts, as well as regulatory variants outside the gene that impact transcription initiation. Current methods for ASE estimation suffer from a number of shortcomings, such as relying on only one variant within a gene, assuming perfect phasing information across multiple variants within a gene, or failing to account for alignment biases and possible genotyping errors. RESULTS: We developed BEASTIE, a Bayesian hierarchical model designed for precise ASE quantification at the gene level, based on given genotypes and RNA-Seq data. BEASTIE addresses the complexities of allelic mapping bias, genotyping error, and phasing errors by incorporating empirical phasing error rates derived from Genome-in-a-Bottle individual NA12878. BEASTIE surpasses existing methods in accuracy, especially in scenarios with high phasing errors. This improvement is critical for identifying rare genetic variants often obscured by such errors. Through rigorous validation on simulated data and application to real data from the 1000 Genomes Project, we establish the robustness of BEASTIE. These findings underscore the value of BEASTIE in revealing patterns of ASE across gene sets and pathways. AVAILABILITY AND IMPLEMENTATION: The software is freely available from Github (https://github.com/x811zou/BEASTIE); and Zendo (DOI: 10.5281/zenodo.15062124).

Bayes Theorem↗

PubMed2025

Bayesian reconstruction and differential testing of excised introns.

MOTIVATION: Characterizing the differential excision of introns is critical for understanding the functional complexity of a cell or tissue, from normal developmental processes to disease pathogenesis. Most transcript reconstruction methods infer full-length transcripts from high-throughput sequencing data. However, this is a challenging task due to incomplete annotations and the heterogeneous expression of transcripts across cell-types, tissues, and experimental conditions. Several recent methods circumvent these difficulties by considering local splicing events, but these methods lose transcript-level splicing information and may conflate similar, but distinct transcripts. RESULTS: In this work, we formalize a new transcript reconstruction problem that interpolates between the full-length and local splicing perspectives by considering sequences of exon-exon junctions (SEEJs) that co-occur in transcripts. We then present a hierarchical Bayesian admixture model and posterior inference algorithms for computing SEEJs (BSEEJ), and a generalized linear model for characterizing differential SEEJ usage based on model parameter estimates. We show that BSEEJ achieves high F1 score for reconstruction tasks and improved accuracy and sensitivity in differential splicing when compared with six transcript and local splicing methods on simulated data. Lastly, we evaluate BSEEJ on experimental data based on transcript reconstruction, novelty of transcripts produced, model sensitivity to hyperparameters, and a functional analysis of differentially expressed SEEJs. AVAILABILITY AND IMPLEMENTATION: BSEEJ is freely available at https://github.com/bayesomicslab/BSEEJ.

Bayes Theorem↗

PubMed2000

Bayesian analysis of mutational spectra.

Studies that examine both the frequency of gene mutation and the pattern or spectrum of mutational changes can be used to identify chemical mutagens and to explore the molecular mechanisms of mutagenesis. In this article, we propose a Bayesian hierarchical modeling approach for the analysis of mutational spectra. We assume that the total number of independent mutations and the numbers of mutations falling into different response categories, defined by location within a gene and/or type of alteration, follow binomial and multinomial sampling distributions, respectively. We use prior distributions to summarize past information about the overall mutation frequency and the probabilities corresponding to the different mutational categories. These priors can be chosen on the basis of data from previous studies using an approach that accounts for heterogeneity among studies. Inferences about the overall mutation frequency, the proportions of mutations in each response category, and the category-specific mutation frequencies can be based on posterior distributions, which incorporate past and current data on the mutant frequency and on DNA sequence alterations. Methods are described for comparing groups and for assessing dose-related trends. We illustrate our approach using data from the literature.

Animals↗

PubMed1996

Estimating defibrillation efficacy using combined upper limit of vulnerability and defibrillation testing.

It is frequently necessary, both clinically and in the laboratory, to estimate how strong a stimulus is required to defibrillate. Current techniques for forming such estimates require the repeated induction of ventricular fibrillation (VF) and subsequent attempts at defibrillation (DF testing). DF testing can be time consuming and in the operating room may increase the patient risks. A novel scheme is presented which combines DF testing with upper limit of vulnerability (ULV) testing. ULV testing is a relatively safe procedure which yields data well correlated with defibrillation efficacy. A Bayesian statistical model of combined ULV/DF testing is presented which is both powerful and concise. The model is used in two examples to design minimum rms error protocols and estimators for the DF95 (the stimulus strength which defibrillates 95% of the time). A simulation for humans of one example solution shows that a single VF episode of combined ULV/DF testing (rms error = 23% of the mean DF95) is better than two VF episodes with DF testing alone (25%). The simulation results for a second example are directly compared with laboratory results from six pigs, showing a less than 1.0% average difference between the simulated and measured rms errors.

Algorithms↗

PubMed1978

Computer-assisted identification of anaerobic bacteria.

A computer program was developed to identify anaerobic bacteria by using simultaneous pattern recognition via a Bayesian probabilistic model. The system is intended for use as a rapid, precise, and reproducible aid in the identification of unknown isolates. The program operates on a data base of 28 genera comprising 238 species of anaerobic bacteria that can be separated by the program. Input to the program consists of biochemical and gas chromatographic test results in binary format. The system is flexible and yields outputs of: (i) most probable species, (ii) significant test results conflicting with established data, and (iii) differential tests of significance for missing test results.

Anaerobiosis↗

PubMed1986

How to construct a subjective index.

We present a method of constructing quantitative indices, which is based on the subjective opinions of a panel of experts, and discuss how a Bayesian probability model and panel opinions can be used together to produce an index. Among the advantages of the method are its face validity and ease of construction. Research shows that when expert opinions are solicited according to certain guidelines, subjective methods may be as accurate as the more objective ones. Guidelines along with a brief report of a recent application are also discussed.

Abstracting and Indexing↗

PubMedDate not supplied

Medical decision making in the choice of a thrombolytic agent for acute myocardial infarction. Quebec Acute Coronary Care Working Group.

Little is known about how physicians make decisions when the evidence is incomplete or controversial. While thrombolysis improves survival following acute myocardial infarction (AMI), conflicting evidence exists as to any specific agent's superiority, particularly if cost-effectiveness is considered. Using a Bayesian hierarchical model, the authors examined the patient, physician, and hospital characteristics that are related to the decision-making process concerning the choice of thrombolytic agent in a prospective registry of 1,165 AMI patients receiving thrombolysis. Tissue plasminogen activator (t-PA) was administered to 432 patients (31.8%) and streptokinase (SK) to the remainder. The presence of an anterior infarction, a previous myocardial infarction, low blood pressure, a cardiologist decision maker, younger age, and receiving treatment within six hours after the start of symptoms were independent predictors of receiving t-PA. The levels of importance that physicians accorded to these patient characteristics differed according to their practicing institutions. Generally, they followed evidence-based medicine and reasonably targeted high-risk patients to receive the more expensive t-PA. However, they also preferentially treated younger patients, where only a small absolute advantage appears to exist.

Aged↗