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PubMed2001

Benchmarking patient outcomes.

PURPOSE: To examine the usefulness of three types of benchmarking for interpreting patient outcome data. DESIGN: This study was part of a multiyear, multihospital longitudinal survey of 10 patient outcomes. The patient outcome used for this methodologic presentation was central line infections (CLI). The sample included eight hospitals in an integrated healthcare system, with a range in size from 144 to 861 beds. The unit of analysis for CLI was the number of line days, with the CLI rate defined as the number of infections per 1,000 patient-line days per month. METHODS: Data on each outcome were collected at the unit level according to standardized protocols. Results were submitted via standardized electronic forms to a central data management center. Data for this presentation were analyzed using a Bayesian hierarchical Poisson model. Results are presented for each hospital and the system as a whole. FINDINGS: In comparison to published benchmarks, hospital performances were mixed with regard to CLI. Five of the 8 hospitals exceeded 2.2 infections per 1,000 patient-line days. When benchmarks were established for each hospital using 95% credible intervals, hospitals did reasonably well with only isolated months reaching or going beyond the benchmark limits. When the entire system was used to establish benchmarks with the 95% credible intervals, the hospitals that reached or exceeded the benchmark limits remained the same, but some hospitals had CLI rates more frequently in the upper 50% of the benchmarking limits. CONCLUSIONS: Benchmarking of quality indicators can be accomplished in a variety of ways as a means to quantify patient care and identify areas needing attention and improvement. Hospital-specific and system-wide benchmarks provide relevant feedback for improving performance at individual hospitals.

Benchmarking↗
PubMed1996

Influence of biochemical parameters of liver function on vancomycin pharmacokinetics.

The influence of biochemical parameters of hepatic function on vancomycin pharmacokinetics was retrospectively evaluated in 76 adult patients (age 18 to 81 years), from biochemistry data gathered during routine therapeutic drug monitoring. All subjects had normal serum creatinine levels. Vancomycin concentrations were determined by fluorescence polarization immunoassay in 101 paired serum samples. All data for vancomycin concentration versus time were fitted to a one-compartment model using the bayesian approach. Bilirubin, transaminases (n = 101), gamma-glutamyl transferase (n = 97), alkaline phosphatase (n = 95), albumin (n = 92) and lactate dehydrogenase (n = 42) were determined. No strong correlation was seen between any of the pharmacokinetic and biochemistry parameters studied. In patients with hyperbilirubinaemia, the mean Vss and t1/2 were increased (Vss: 0.75 +/- 0.31 versus 0.92 +/- 0.42 1.kg-1, p = 0.020; t1/2 5.93 +/- 3.30 versus 7.48 +/- 4.44 hr, p = 0.049). When liver function was evaluated according to hepatic profile (normal, mildly altered and severely altered), no significant differences were observed in vancomycin pharmacokinetics among the groups. In conclusion, vancomycin pharmacokinetics are only weakly influenced by the biochemistry parameters of liver function.

Adolescent↗
PubMed2006

Operon prediction for sequenced bacterial genomes without experimental information.

Various computational approaches have been proposed for operon prediction, but most algorithms rely on experimental or functional data that are only available for a small subset of sequenced genomes. In this study, we explored the possibility of using phylogenetic information to aid in operon prediction, and we constructed a Bayesian hidden Markov model that incorporates comparative genomic data with traditional predictors, such as intergenic distances. The prediction algorithm performs as well as the best previously reported method, with several significant advantages. It uses fewer data sources and so it is easier to implement, and the method is more broadly applicable than previous methods--it can be applied to essentially every gene in any sequenced bacterial genome. Furthermore, we show that near-optimal performance is easily reached with a generic set of comparative genomes and does not depend on a specific relationship between the subject genome and the comparative set. We applied the algorithm to the Bacillus anthracis genome and found that it successfully predicted all previously verified B. anthracis operons. To further test its performance, we chose a predicted operon (BA1489-92) containing several genes with little apparent functional relatedness and tested their cotranscriptional nature. Experimental evidence shows that these genes are cotranscribed, and the data have interesting implications for B. anthracis biology. Overall, our findings show that this algorithm is capable of highly sensitive and accurate operon prediction in a wide range of bacterial genomes and that these predictions can lead to the rapid discovery of new functional relationships among genes.

Algorithms↗
PubMed2006

Comparative phylogenomics of Clostridium difficile reveals clade specificity and microevolution of hypervirulent strains.

Clostridium difficile is the most frequent cause of nosocomial diarrhea worldwide, and recent reports suggested the emergence of a hypervirulent strain in North America and Europe. In this study, we applied comparative phylogenomics (whole-genome comparisons using DNA microarrays combined with Bayesian phylogenies) to model the phylogeny of C. difficile, including 75 diverse isolates comprising hypervirulent, toxin-variable, and animal strains. The analysis identified four distinct statistically supported clusters comprising a hypervirulent clade, a toxin A(-) B(+) clade, and two clades with human and animal isolates. Genetic differences among clades revealed several genetic islands relating to virulence and niche adaptation, including antibiotic resistance, motility, adhesion, and enteric metabolism. Only 19.7% of genes were shared by all strains, confirming that this enteric species readily undergoes genetic exchange. This study has provided insight into the possible origins of C. difficile and its evolution that may have implications in disease control strategies.

Animals↗
PubMed2026

Investigating the zoonotic origins of ESBL-producing E. coli in community-acquired urinary tract infections in Ecuador.

Extended-spectrum β-lactamase-producing Escherichia coli (ESBL-producing E. coli) pose a growing global health threat. Although Latin America has been identified as a global hotspot of antimicrobial resistance, the zoonotic contribution to drug-resistant infections in the region remains poorly defined. We analyzed 137 clinical ESBL-producing E. coli isolates from urinary tract infections (UTIs) in Quito, Ecuador, applying a Bayesian latent class model informed by host-associated mobile genetic elements to estimate the fraction of infections attributable to food-animal sources. We estimated that 25.5% (35/137) of UTI isolates were putative zoonotic cases. This proportion rose to 42.5% after excluding ST131-H30, a human-associated pandemic lineage. Putative zoonotic isolates were enriched for animal-associated β-lactamase genes (e.g., blaTEM-1B, blaCTX-M-65), lacked human-associated markers such as blaOXA-1, and exhibited diverse antimicrobial resistance gene profiles resembling those observed among food-animal isolates. These isolates were also enriched for ColV-associated virulence genes typically linked to avian pathogenic E. coli. Putative zoonotic strains contributed substantially to third-generation cephalosporin-resistant UTIs in Quito, Ecuador, challenging assumptions derived from high-income settings that such infections are driven predominantly by human-to-human transmission. These findings highlight the importance of integrated One Health surveillance and mitigation, particularly in low- and middle-income countries where gaps in water, sanitation, and hygiene (WASH) may interact with antimicrobial use in food production to amplify antimicrobial resistance transmission.IMPORTANCEESBL-producing E. coli have rapidly emerged as a major global antimicrobial resistance threat. In Latin America, cephalosporins are commonly used in food-animal production, fueling the emergence of ESBL-producing E. coli. In low- and middle-income countries, excessive antimicrobial use driven by poorly regulated over-the-counter sales, combined with inadequate water, sanitation, and hygiene (WASH) infrastructure, can facilitate antimicrobial-resistant pathogen transmission from food animals to humans. Using a novel statistical-genomic approach, we found that over one in four cephalosporin-resistant UTIs in Quito, Ecuador, may be caused by E. coli strains originating from food animals. Our findings highlight the public health risks associated with antimicrobial use in food-animal production and the role of environmental and infrastructure-related vulnerabilities. As global demand for animal protein continues rising in middle-income countries, controlling zoonotic antimicrobial resistance transmission becomes increasingly urgent for protecting human health through integrated One Health strategies.

ESBL-producing E. coli↗
PubMed2005

Incidence of sports and recreation related injuries resulting in hospitalization in Wisconsin in 2000.

OBJECTIVE: To describe the incidence and patterns of sports and recreation related injuries resulting in inpatient hospitalization in Wisconsin. Although much sports and recreation related injury research has focused on the emergency department setting, little is known about the scope or characteristics of more severe sports injuries resulting in hospitalization. SETTING: The Wisconsin Bureau of Health Information (BHI) maintains hospital inpatient discharge data through a statewide mandatory reporting system. The database contains demographic and health information on all patients hospitalized in acute care non-federal hospitals in Wisconsin. METHODS: The authors developed a classification scheme based on the International Classification of Diseases External cause of injury code (E code) to identify hospitalizations for sports and recreation related injuries from the BHI data files (2000). Due to the uncertainty within E codes in specifying sports and recreation related injuries, the authors used Bayesian analysis to model the incidence of these types of injuries. RESULTS: There were 1714 (95% credible interval 1499 to 2022) sports and recreation-related injury hospitalizations in Wisconsin in 2000 (32.0 per 100,000 population). The most common mechanisms of injury were being struck by/against an object in sports (6.4 per 100,000 population) and pedal cycle riding (6.2 per 100,000). Ten to 19 year olds had the highest rate of sports and recreation related injury hospitalization (65.3 per 100,000 population), and males overall had a rate four times higher than females. CONCLUSIONS: Over 1700 sports and recreation related injuries occurred in Wisconsin in 2000 that were treated during an inpatient hospitalization. Sports and recreation activities result in a substantial number of serious, as well as minor injuries. Prevention efforts aimed at reducing injuries while continuing to promote participation in physical activity for all ages are critical.

Adolescent↗
PubMed2006

Remapping in human visual cortex.

With each eye movement, stationary objects in the world change position on the retina, yet we perceive the world as stable. Spatial updating, or remapping, is one neural mechanism by which the brain compensates for shifts in the retinal image caused by voluntary eye movements. Remapping of a visual representation is believed to arise from a widespread neural circuit including parietal and frontal cortex. The current experiment tests the hypothesis that extrastriate visual areas in human cortex have access to remapped spatial information. We tested this hypothesis using functional magnetic resonance imaging (fMRI). We first identified the borders of several occipital lobe visual areas using standard retinotopic techniques. We then tested subjects while they performed a single-step saccade task analogous to the task used in neurophysiological studies in monkeys, and two conditions that control for visual and motor effects. We analyzed the fMRI time series data with a nonlinear, fully Bayesian hierarchical statistical model. We identified remapping as activity in the single-step task that could not be attributed to purely visual or oculomotor effects. The strength of remapping was roughly monotonic with position in the visual hierarchy: remapped responses were largest in areas V3A and hV4 and smallest in V1 and V2. These results demonstrate that updated visual representations are present in cortical areas that are directly linked to visual perception.

Acoustic Stimulation↗
PubMed2000

Approximate maximum entropy joint feature inference consistent with arbitrary lower-order probability constraints: application to statistical classification

We propose a new learning method for discrete space statistical classifiers. Similar to Chow and Liu (1968) and Cheeseman (1983), we cast classification/inference within the more general framework of estimating the joint probability mass function (p.m.f.) for the (feature vector, class label) pair. Cheeseman's proposal to build the maximum entropy (ME) joint p.m.f. consistent with general lower-order probability constraints is in principle powerful, allowing general dependencies between features. However, enormous learning complexity has severely limited the use of this approach. Alternative models such as Bayesian networks (BNs) require explicit determination of conditional independencies. These may be difficult to assess given limited data. Here we propose an approximate ME method, which, like previous methods, incorporates general constraints while retaining quite tractable learning. The new method restricts joint p.m.f. support during learning to a small subset of the full feature space. Classification gains are realized over dependence trees, tree-augmented naive Bayes networks, BNs trained by the Kutato algorithm, and multilayer perceptrons. Extensions to more general inference problems are indicated. We also propose a novel exact inference method when there are several missing features.

Journal Article↗
PubMed2001

Correctness of belief propagation in Gaussian graphical models of arbitrary topology.

Graphical models, such as Bayesian networks and Markov random fields, represent statistical dependencies of variables by a graph. Local "belief propagation" rules of the sort proposed by Pearl (1988) are guaranteed to converge to the correct posterior probabilities in singly connected graphs. Recently, good performance has been obtained by using these same rules on graphs with loops, a method we refer to as loopy belief propagation. Perhaps the most dramatic instance is the near Shannon-limit performance of "Turbo codes," whose decoding algorithm is equivalent to loopy propagation. Except for the case of graphs with a single loop, there has been little theoretical understanding of loopy propagation. Here we analyze belief propagation in networks with arbitrary topologies when the nodes in the graph describe jointly gaussian random variables. We give an analytical formula relating the true posterior probabilities with those calculated using loopy propagation. We give sufficient conditions for convergence and show that when belief propagation converges, it gives the correct posterior means for all graph topologies, not just networks with a single loop. These results motivate using the powerful belief propagation algorithm in a broader class of networks and help clarify the empirical performance results.

Journal Article↗
PubMed1997

Selecting optimal experiments for multiple output multilayer perceptrons.

Where should a researcher conduct experiments to provide training data for a multilayer perceptron? This question is investigated, and a statistical method for selecting optimal experimental design points for multiple output multilayer perceptrons is introduced. Multiple class discrimination problems are examined using a framework in which the multilayer perceptron is viewed as a multivariate nonlinear regression model. Following a Bayesian formulation for the case where the variance-covariance matrix of the responses is unknown, a selection criterion is developed. This criterion is based on the volume of the joint confidence ellipsoid for the weights in a multilayer perceptron. An example is used to demonstrate the superiority of optimally selected design points over randomly chosen points, as well as points chosen in a grid pattern. Simplification of the basic criterion is offered through the use of Hadamard matrices to produce uncorrelated outputs.

Algorithms↗
PubMedDate not supplied

A genetic and spatial Bayesian analysis of mastitis resistance.

A nationwide health card recording system for dairy cattle was introduced in Norway in 1975 (the Norwegian Cattle Health Services). The data base holds information on mastitis occurrences on an individual cow basis. A reduction in mastitis frequency across the population is desired, and for this purpose risk factors are investigated. In this paper a Bayesian proportional hazards model is used for modelling the time to first veterinary treatment of clinical mastitis, including both genetic and environmental covariates. Sire effects were modelled as shared random components, and veterinary district was included as an environmental effect with prior spatial smoothing. A non-informative smoothing prior was assumed for the baseline hazard, and Markov chain Monte Carlo methods (MCMC) were used for inference. We propose a new measure of quality for sires, in terms of their posterior probability of being among the, say 10% best sires. The probability is an easily interpretable measure that can be directly used to rank sires. Estimating these complex probabilities is straightforward in an MCMC setting. The results indicate considerable differences between sires with regards to their daughters disease resistance. A regional effect was also discovered with the lowest risk of disease in the south-eastern parts of Norway.

Animals↗
PubMed2005

Does alendronate reduce the risk of fracture in men? A meta-analysis incorporating prior knowledge of anti-fracture efficacy in women.

BACKGROUND: Alendronate has been found to reduce the risk of fractures in postmenopausal women as demonstrated in multiple randomized controlled trials enrolling thousands of women. Yet there is a paucity of such randomized controlled trials in osteoporotic men. Our objective was to systematically review the anti-fracture efficacy of alendronate in men with low bone mass or with a history of prevalent fracture(s) and incorporate prior knowledge of alendronate efficacy in women in the analysis. METHODS: We examined randomized controlled trials in men comparing the anti-fracture efficacy of alendronate to placebo or calcium or vitamin D, or any combination of these. Studies of men with secondary causes of osteoporosis other than hypogonadism were excluded. We searched the following electronic databases (without language restrictions) for potentially relevant citations: Medline, Medline in Process (1966-May 24/2004), and Embase (1996-2004). We also contacted the manufacturer of the drug in search of other relevant trials. Two reviewers independently identified two trials (including 375 men), which met all inclusion criteria. Data were abstracted by one reviewer and checked by another. Results of the male trials were pooled using Bayesian random effects models, incorporating prior information of anti-fracture efficacy from meta-analyses of women. RESULTS: The odds ratios of incident fractures in men (with 95% credibility intervals) with alendronate (10 mg daily) were: vertebral fractures, 0.44 (0.23, 0.83) and non-vertebral fractures, 0.60 (0.29, 1.44). CONCLUSION: In conclusion, alendronate decreases the risk of vertebral fractures in men at risk. There is currently insufficient evidence of a statistically significant reduction of non-vertebral fractures, but the paucity of trials in men limit the statistical power to detect such an effect.

Adult↗
PubMed2006

Spatio-temporal analysis of the role of climate in inter-annual variation of malaria incidence in Zimbabwe.

BACKGROUND: On the fringes of endemic zones climate is a major determinant of inter-annual variation in malaria incidence. Quantitative description of the space-time effect of this association has practical implications for the development of operational malaria early warning system (MEWS) and malaria control. We used Bayesian negative binomial models for spatio-temporal analysis of the relationship between annual malaria incidence and selected climatic covariates at a district level in Zimbabwe from 1988-1999. RESULTS: Considerable inter-annual variations were observed in the timing and intensity of malaria incidence. Annual mean values of average temperature, rainfall and vapour pressure were strong positive predictors of increased annual incidence whereas maximum and minimum temperature had the opposite effects. Our modelling approach adjusted for unmeasured space-time varying risk factors and showed that while year to year variation in malaria incidence is driven mainly by climate, the resultant spatial risk pattern may to large extent be influenced by other risk factors except during high and low risk years following the occurrence of extremely wet and dry conditions, respectively. CONCLUSION: Our model revealed a spatially varying risk pattern that is not attributable only to climate. We postulate that only years characterized by extreme climatic conditions may be important for developing climate based MEWS and for delineating areas prone to climate driven epidemics. However, the predictive value of climatic risk factors identified in this study still needs to be evaluated.

Bayes Theorem↗
PubMed2025

Bayesian classification of OXPHOS deficient skeletal myofibres.

Mitochondria are organelles in most human cells which release the energy required for cells to function. Oxidative phosphorylation (OXPHOS) is a key biochemical process within mitochondria required for energy production and requires a range of proteins and protein complexes. Mitochondria contain multiple copies of their own genome (mtDNA), which codes for some of the proteins and ribonucleic acids required for mitochondrial function and assembly. Pathology arises from genetic defects in mtDNA and can reduce cellular abundance of OXPHOS proteins, affecting mitochondrial function. Due to the continuous turn-over of mtDNA, pathology is random and neighbouring cells can possess different OXPHOS protein abundance. Estimating the proportion of cells where OXPHOS protein abundance is too low to maintain normal function is critical to understanding disease severity and predicting disease progression. Currently, one method to classify single cells as being OXPHOS deficient is prevalent in the literature. The method compares a patient's OXPHOS protein abundance to that of a small number of healthy control subjects. If the patient's cell displays an abundance which differs from the abundance of the controls then it is deemed deficient. However, due to the natural variation between subjects and the low number of control subjects typically available, this method is inflexible and often results in a large proportion of patient cells being misclassified. These misclassifications have significant consequences for the clinical interpretation of these data. We propose a single-cell classification method using a Bayesian hierarchical mixture model, which allows for inter-subject OXPHOS protein abundance variation. The model accurately classifies an example dataset of OXPHOS protein abundances in skeletal muscle fibres (myofibres). When comparing the proposed and existing model classifications to manual classifications performed by experts, the proposed model results in estimates of the proportion of deficient myofibres that are consistent with expert manual classifications.

Oxidative Phosphorylation↗
PubMed2006

Genetic partitioning of variation in ovulatory follicle size and probability of pregnancy in beef cattle.

The objectives of this research were to partition variation in ovulatory follicle size into genetic and nongenetic components and to assess the utility of ovulatory follicle size as an indicator trait associated with reproductive success in beef cattle. Data were collected during the years 2002 to 2005 from 780 beef females that ranged in age from 1 to 12 yr (mean of 2.4 observations per female). Data were analyzed with a multiple trait Gibbs sampler for animal models to make Bayesian inferences from flat priors. A chain of 500,000 Gibbs samples was thinned to every 200th sample to produce a posterior distribution composed of 2,500 samples. Heritability estimates (posterior mean +/- SD) were 0.16 +/- 0.03 for follicle size and 0.07 +/- 0.02 and 0.02 +/- 0.01 for pregnancy rate as a trait of the female and service sire, respectively. Posterior means of genetic correlations were all <0.10, with 0.00 contained within the respective 90% probability density posterior intervals. Results indicate that whereas follicle size is of greater heritability than pregnancy rate, its usefulness to improve reproductive rate is greatest as an ancillary phenotype in multiple trait selection.

Animals↗
PubMed2002

Frequency and heritability of supernumerary teats in German simmental and German Brown Swiss cows.

The incidence of supernumerary teats has been recorded in 179,793 German Simmental and 37,460 German Brown Swiss cows. Data were collected from first-crop daughters of test bulls from 1987 to 1998. The number of sires was 4,298 and 1,039, respectively. The average frequency of affected animals was 44.3% in German Simmental and 31.2% in German Brown Swiss. A significant yet small effect was found for herd-book membership (yes/no) and, in the Simmental data only, for inspector. The impact of year of birth and year of inspection was also significant, and more important, reflected a decrease of the population averages with time. Surprisingly, the incidence of supernumerary teats increased significantly with the parity number of dams in both breeds. A Bayesian threshold animal model approach was used to estimate the heritability of the occurrence of supernumerary teats. The posterior mean for the heritability was h2 = 0.45 in German Simmental and h2 = 0.43 in Brown Swiss, with standard errors of 0.01 and 0.03, respectively. Ranks of sires obtained from threshold and linear models showed a rank correlation of roughly 0.8 in both breeds. For a sound identification of the worst sires, a threshold model is recommended.

Animals↗
PubMed1998

Computer-adjusted dosage of anticoagulant therapy improves the quality of anticoagulation.

OBJECTIVE: Risks and benefits of anticoagulant therapy depend directly of the quality of anticoagulation. We performed a meta-analysis of published randomized trials to assess the overall effectiveness of computer-based prescription systems on the quality of anticoagulation. DESIGN: Randomized controlled trials were identified through electronic searches of the Medline database (1966-1997) and systematic analyses of the references of articles. Two investigators selected relevant papers and summarized data from the studies. METHODS: The outcome variable was the proportion of days within the target range of anticoagulation. A pooled estimate of the common odds ratio of being in the target range and its confidence interval was obtained by the Mantel-Haenszel method. RESULTS: Seven trials having included 1217 patients were identified. Computer systems were based on a pharmacokinetic-pharmacodynamic model and a bayesian prediction method. Most of them concerned the oral anticoagulant warfarin. The global odds ratio of being in the target range was 1.58 [95% CI: 1.34-1.86], thus meaning that the use of a computer for anticoagulation optimization increased by 58% the proportion of visits where patients were appropriately treated. The proportion of clinical events was too low for allowing a summary analysis. CONCLUSION: Evidence from randomized controlled trials supports the effectiveness of computer-aided anticoagulant prescription. Diffusion of these systems in ambulatory care could increase the benefit/risk ratio of anticoagulant treatment at a low cost.

Anticoagulants↗
PubMed2002

Multiscale and Bayesian approaches to data analysis in genomics high-throughput screening.

Tremendous amounts of data are produced by high-throughput screening methods currently employed in drug discovery and product development. A typical cDNA microarray or oligonucleotide-based gene chip experiment easily generates over 10,000 data points for each array or chip. The challenge of inferring meaningful information is formidable given the size and number of these datasets. This paper reviews the current status of statistical tools available for gene expression analysis, with emphasis on Bayesian approaches and multiscale wavelet filtering. Fundamental concepts of Bayesian and multiscale modeling are discussed from the perspective of their potential to address important issues related to the analysis of gene expression data, such as the fact that genomic data often have non-Gaussian distributions and feature localization and multiple scales in both frequency and measurement dimension. Recent publications in these areas are reviewed. Wavelet filtering and the advantages of multiscale methods are demonstrated by application to publicly available gene expression data from the National Cancer Institute (NCI). Multiscale methods, including multiscale principal component analysis (MSPCA), are applied to extract gene subsets and to visualize data in multidimensions for comparisons. Similarity in cell lines and gene selection are effectively visualized and quantitatively compared.

Animals↗