Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “probabilistic modelling”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,369 records · Page 76Linked to original sources
PubMedDate not supplied

Cost-effectiveness and cost-utility of long-term management strategies for heartburn.

OBJECTIVES: To compare the expected costs and outcomes of seven alternative long-term primary care strategies for the management of patients with moderate-to-severe heartburn over a 1-year period. METHODS: A decision-analytic model was developed to estimate costs and effects (weeks with heartburn symptoms and quality adjusted life years [QALYs]) for each strategy. Meta-analyses were used to synthesize acute treatment and maintenance studies and physician surveys to collect information on patient management. The impact of uncertainty on the base case results was assessed using probabilistic sensitivity analysis. Probability distributions were defined for key model parameters and techniques of Monte Carlo simulation were used to draw values from these distributions. Cost-effectiveness acceptability curves (CEACs) conditional on the monetary value decision makers are willing to pay for a symptom-free day or QALY were created for each strategy. RESULTS: In the base case, no strategy was strictly dominated by any other strategy. However, two strategies (maintenance H2-receptor antagonists H2RA] and step-down proton pump inhibitor PPI]) were dominated through principles of extended dominance. The least costly and least effective strategy was intermittent H2RA, while maintenance PPI was the most costly and most effective. CONCLUSIONS: This analysis showed that the best way of managing patients with heartburn depends on how much society is willing to pay to achieve health improvements. Based on the commonly quoted threshold of US 50,000 dollars per QALY, the optimal primary care strategy for managing patients with moderate-to-severe heartburn symptoms is to treat the symptoms with a PPI followed by maintenance therapy with an H2RA to prevent symptomatic recurrence.

Canada↗
PubMed2007

Cost effectiveness of palivizumab for respiratory syncytial virus prophylaxis in high-risk children: a UK analysis.

OBJECTIVE: To assess the cost effectiveness of palivizumab (a preventative treatment against severe respiratory syncytial virus [RSV] infection) in children at high risk of hospitalisation, i.e. preterm infants < or = 35 weeks gestation, children with bronchopulmonary dysplasia (BPD) and children with congenital heart disease (CHD). METHODS: A decision tree model was developed employing data sources from the published literature, palivizumab clinical trials, official UK price/tariff lists and national population statistics. The comparator was no prophylaxis. The primary perspective of the study was that of the UK NHS. In a societal perspective scenario analysis, the future lost productivity of a child resulting from RSV-related mortality (indirect costs) was also included. The cost of administration of palivizumab, hospital care for RSV infections and the cost of asthma treatment were included. The analysis was based on a lifetime follow-up period in order to capture the impact of palivizumab on long-term morbidity and mortality resulting from an RSV infection. The primary efficacy outcome in the palivizumab clinical trials was the number of RSV hospitalisations avoided, which was extrapolated to effectiveness outcomes, i.e. number of life-years gained and number of QALYs. Costs and effects were discounted by 3.5%. RESULTS: In preterm infants and children with BPD, prophylaxis with palivizumab compared with no prophylaxis had an incremental cost-effectiveness ratio (ICER) of 7042 pounds/QALY without discounting outcomes, increasing to 16,720 pounds/QALY after discounting. In babies with CHD, the use of palivizumab resulted in an ICER of 2427 pounds/QALY without discounting outcomes and 6664 pounds/QALY after discounting. One-way sensitivity analyses and probabilistic sensitivity analyses confirmed the robustness of the model. A scenario analysis showed that the inclusion of indirect costs leads to further improvement in the cost-effectiveness outcomes for palivizumab. CONCLUSION: This study suggests that palivizumab prophylaxis against severe RSV infection in children at high risk may be cost effective from the NHS perspective (vs no prophylaxis), and that the positive clinical and economic benefits may persist beyond one RSV season.

Antibodies, Monoclonal↗
PubMed2003

A comparison of model performance for six quantitative structure-activity relationship packages that predict acute toxicity to fish.

Some regulatory programs rely on quantitative structure-activity relationship (QSAR) models to predict toxic effects to biota. Many currently existing QSAR models can predict the effects of a wide range of substances to biota, particularly aquatic biota. The difficulty for regulatory programs is in choosing the appropriate QSAR model or models for application in their new and existing substances programs. We evaluated model performance of six QSAR modeling packages: Ecological Structure Activity Relationship (ECOSAR), TOPKAT, a Probabilistic Neural Network (PNN), a Computational Neural Network (CNN), the QSAR components of the Assessment Tools for the Evaluation of Risk (ASTER) system, and the Optimized Approach Based on Structural Indices Set (OASIS) system. Using a testing data set of 130 substances that had not been included in the training data sets of the QSAR models under consideration, we compared model predictions for 96-h median lethal concentrations (LC50s) to fathead minnows to the corresponding measured toxicity values available in the AQUIRE database. The testing data set was heavily weighted with neutral organics of low molecular weight and functionality. Many of the testing data set substances also had a nonpolar narcosis mode of action and/or were chlorinated. A variety of statistical measures (correlation coefficient, slope and intercept from a linear regression analysis, mean absolute and squared difference between log prediction and log measured toxicity, and the percentage of predictions within factors of 2, 5, 10, 100, and 1,000 of measured toxicity values) indicated that the PNN model had the best model performance for the full testing data set of 130 substances. The rank order of the remainder of the models depended on the statistical measure employed. TOPKAT also had excellent model performance for substances within its optimum prediction space. Only 37% of the substances in the testing data set, however, fell within this optimum prediction space.

Animals↗
PubMedDate not supplied

Using general regression and probabilistic neural networks to predict human intestinal absorption with topological descriptors derived from two-dimensional chemical structures.

The objective of this study was to develop rapid and reliable methods to predict the percent human intestinal absorption (%HIA) of compounds based on their 2D descriptors. The analyzed data set included 86 drug and drug-like molecules and was the same as that studied by Wessel and co-workers. Instead of using three-dimensional descriptors such as polar surface area, which require lengthy computations, we employed only two-dimensional topological descriptors derived from information about the two-dimensional structure of molecules. The %HIA values were modeled using a general regression neural network (GRNN) and a probabilistic neural network (PNN), variants of normalized radial basis function networks. Both networks performed well to model the %HIA values. The root-mean square (rms) error was 22.8 %HIA unit for the external prediction set for a GRNN model, and 80% of the external prediction set was correctly classified for a PNN model, indicating the potential of our approach to estimate the %HIA values for a large set of compounds as virtual libraries.

Humans↗
PubMed1979

Correlation between cell size and position within the division cycle in suspension cultures of Chang liver cells.

Chang liver cells from exponentially growing suspension cultures have been separated by sedimentation at unit gravity. Determinations of the protein content per cell showed that the fractionation procedure resulted in good separation of cells of different size. On the other hand, the DNA content of individual cells from the fractions, as determined cytofluorimetrically, indicated considerable heterogeneity in the size of cells from the same stage of the division cycle. On the basis of earlier results on intermitotic growth and the variation in the length of the cell cycle in homogeneous cell populations, a mathematical model has been constructed and tested using a computer program. The present results on the size distribution of cells from the different stages of the mitotic cycle are consistent with a regeneration of size heterogeneity in each cell generation, as a result of the dispersion of intermitotic times. The variation in cell cycle times may be related to a probabilistic event in the G1 period. In the mathematical model it was necessary to include a mechanism by which the regeneration of abnormally large cells is prevented. The experimental data are compatible with a gradually increasing inhibition of growth in cells larger than a certain size (circa 400 pg protein per cell).

Animals↗
PubMed2006

Precise physical models of protein-DNA interaction from high-throughput data.

A cell's ability to regulate gene transcription depends in large part on the energy with which transcription factors (TFs) bind their DNA regulatory sites. Obtaining accurate models of this binding energy is therefore an important goal for quantitative biology. In this article, we present a principled likelihood-based approach for inferring physical models of TF-DNA binding energy from the data produced by modern high-throughput binding assays. Central to our analysis is the ability to assess the relative likelihood of different model parameters given experimental observations. We take a unique approach to this problem and show how to compute likelihood without any explicit assumptions about the noise that inevitably corrupts such measurements. Sampling possible choices for model parameters according to this likelihood function, we can then make probabilistic predictions for the identities of binding sites and their physical binding energies. Applying this procedure to previously published data on the Saccharomyces cerevisiae TF Abf1p, we find models of TF binding whose parameters are determined with remarkable precision. Evidence for the accuracy of these models is provided by an astonishing level of phylogenetic conservation in the predicted energies of putative binding sites. Results from in vivo and in vitro experiments also provide highly consistent characterizations of Abf1p, a result that contrasts with a previous analysis of the same data.

Binding Sites↗
PubMed1991

Cell cycle kinetics with supramitotic control, two cell types, and unequal division: a model of transformed embryonic cells.

We develop a mathematical model of cell cycle kinetics of transformed embryonic cells. The model includes supramitotic regulation, in which decisions regarding growth control are made at a point inside the cell division cycle and their impact extends to the next decision point, located in the next division cycle. Another feature is the presence of two varieties of cells, which switch from one to the other with given transition probabilities. The third factor considered is unequal division of cells, also defined in probabilistic terms. We provide a rigorous description of the model and derivation of its equations and analyze its asymptotic properties by defining and investigating an abstract semigroup of positive linear operators in appropriate state space. The spectral properties of the semigroup yield the balanced exponential growth law for the model. To compare the model to experimental data, we derive basic pedigree statistics, beta curves, and generation time correlations. We present numerical calculations based on measurements available for the embryonic cells. We conclude that to yield the experimentally obtained pedigree statistics, switches from one cell variety to the other must be quite infrequent.

Animals↗
PubMed2005

Managing fatigue: it's about sleep.

Fatigue has increasingly been viewed by society as a safety hazard. This has lead to increased regulation of fatigue by governments. The most common control process has been compliance with prescriptive hours of service (HOS) rule sets. Despite the frequent use of prescriptive rule sets, there is an emerging consensus that they are an ineffective hazard control, based on poor scientific defensibility and lack of operational flexibility. In exploring potential alternatives, we propose a shift from prescriptive HOS limitations toward a broader Safety management system (SMS) approach. Rather than limiting HOS, this approach provides multiple layers of defence, whereby fatigue-related incidents are the final layer of many in an error trajectory. This review presents a conceptual basis for managing the first two levels of an error trajectory for fatigue. The concept is based upon a prior sleep/wake model, which determines fatigue-risk thresholds by the amount of sleep individuals have acquired in the prior 24 and 48 h. In doing so, managing level 1 of the error trajectory involves the implementation of systems that determine probabilistic sleep opportunity, such as prescriptive HOS rules or fatigue modelling. Managing level 2, requires individuals to be responsible for monitoring their own prior sleep and wake to determine individual fitness for duty. Existing subjective, neurobehavioral and electrophysiological research is reviewed to make preliminary recommendations for sleep and wake thresholds. However, given the lack of task- and industry-specific data, any definitive conclusions will rely in post-implementation research to refine the thresholds.

Accidents, Occupational↗
PubMed1998

On the appropriateness of marginal models for repeated measurements in clinical trials.

Although models developed directly to describe marginal distributions have become widespread in the analysis of repeated measurements, some of their disadvantages are not well enough known. These include producing profile curves that correspond to no possible individual, possibly showing that a treatment is superior on average when it is poorer for each individual subject, implicitly generating complex and implausible physiological explanations, including underdispersion in subgroups, and sometimes corresponding to no possible probabilistic data generating mechanism. We conclude that such marginal models may sometimes be appropriate for descriptive observational studies, such as sample surveys in epidemiology, but should only be used with great care in causal experimental settings, such as clinical trials.

Clinical Trials as Topic↗
PubMed2006

Heterotachy processes in rhodophyte-derived secondhand plastid genes: Implications for addressing the origin and evolution of dinoflagellate plastids.

Serial transfer of plastids from one eukaryotic host to another is the key process involved in evolution of secondhand plastids. Such transfers drastically change the environment of the plastids and hence the selection regimes, presumably leading to changes over time in the characteristics of plastid gene evolution and to misleading phylogenetic inferences. About half of the dinoflagellate protists species are photosynthetic and unique in harboring a diversity of plastids acquired from a wide range of eukaryotic algae. They are therefore ideal for studying evolutionary processes of plastids gained through secondary and tertiary endosymbioses. In the light of these processes, we have evaluated the origin of 2 types of dinoflagellate plastids, containing the peridinin or 19'-hexanoyloxyfucoxanthin (19'-HNOF) pigments, by inferring the phylogeny using "covarion" evolutionary models allowing the pattern of among-site rate variation to change over time. Our investigations of genes from secondary and tertiary plastids derived from the rhodophyte plastid lineage clearly reveal "heterotachy" processes characterized as stationary covarion substitution patterns and changes in proportion of variable sites across sequences. Failure to accommodate covarion-like substitution patterns can have strong effects on the plastid tree topology. Importantly, multigene analyses performed with probabilistic methods using among-site rate and covarion models of evolution conflict with proposed single origin of the peridinin- and 19'-HNOF-containing plastids, suggesting that analysis of secondhand plastids can be hampered by convergence in the evolutionary signature of the plastid DNA sequences. Another type of sequence convergence was detected at protein level involving the psaA gene. Excluding the psaA sequence from a concatenated protein alignment grouped the peridinin plastid with haptophytes, congruent with all DNA trees. Altogether, taking account of complex processes involved in the evolution of dinoflagellate plastid sequences (both at the DNA and amino acid level), we demonstrate the difficulty of excluding independent, tertiary origin for both the peridinin and 19'-HNOF plastids involving engulfment of haptophyte-like algae. In addition, the refined topologies suggest the red algal order, Porphyridales, as the endosymbiont ancestor of the secondary plastids in cryptophytes, haptophytes, and heterokonts.

Animals↗
PubMed1998

Is the hippocampus a Kalman filter?

Based on a large body of neurophysiological, neuroanatomical, and behavioral data, it has been suggested that the hippocampal formation serves as a spatial learning and localization system. This spatial representation is metric in nature and arises as a result of associations between sensory inputs and dead-reckoning information generated by the animal. However, despite the fact that these two information streams provide uncertain information (e.g., recognition errors, dead-reckoning drifts, etc.), the hippocampal computational models suggested to date have not explicitly addressed information fusion from erroneous sources. In this paper we develop a computational model of hippocampal spatial learning and relate its functioning to a probabilistic tool used for uncertain sensory fusion in robots: the Kalman filter. This parallel allows us to derive statistically optimal update expressions for the localization performed by our computational model.

Animals↗
PubMed2002

Evaluation of permeability of microporous media, using the modified random-trajectory approach.

The random trajectory approach derived recently for the purpose of evaluation of the percolation threshold is modified and applied to the modeling of permeability. The main modification consists in probabilistic accounting of possible trajectories, the total permeability being evaluated as a sum over all available percolation trajectories, without any preferences in orientation. Results of calculations of permeability vs porosity, sample thickness, and other structural factors are presented. It is concluded that the qualitative tendencies regarding permeability do not significantly differ from those found before for percolation.

Journal Article↗
PubMed2003

Integrating the roles of information and competitive ability on the spatial distribution of social foragers.

Understanding and predicting the spatial distribution of social foragers among patchily distributed resources is a problem that has been addressed with numerous approaches over the 30 yr since the ideal free distribution (IFD) was first introduced. The two main approaches involve perceptual constraints and unequal competitors. Here we present a model of social foragers choosing among resource patches. Each forager makes a probabilistic choice on the basis of the information acquired through past foraging experiences. Food acquisition is determined by the forager's competitive ability. This model predicts that perceptual constraints have a greater influence on the spatial distribution of foragers than unequal competitive abilities but that competitive ability plays an important role in determining an individual's information state and behavior. Better competitors have access to more information; consequently, we find that competitive abilities and perceptual constraints are integrated through the social environment occupied by individual foragers. Relative competitive abilities influence the forager's information state, and the ability to use information determines the resulting spatial distribution.

Animals↗
PubMed1999

Uncertainty of the tritium dose conversion factor.

Environmental releases of tritium oxide at a number of Department of Energy nuclear weapons facilities contribute to a significant portion of environmental dose. Several conversion factors are utilized in the estimation of human impact from these releases, e.g., dispersion coefficients, consumption rates, uptake factors, transport factors, dose conversion factors, and risk coefficients. A probabilistic determination of the tritium dose conversion factor was generated in this work to assess the uncertainty of the internal dosimetry required to estimate dose equivalent given an intake of tritium oxide. The tritium dose conversion factor was found to vary by a factor of about 15 with a median value of 2.2 x 10(-11) Sv Bq(-1) when considering orthovoltage x rays as the standard for estimating the relative biological effectiveness of tritium. The median dose conversion factor increases by about 50%; however, when gamma radiation is considered as the standard. The current deterministic estimate of the tritium dose conversion factor published by the DOE and the EPA is 1.7 x 10(-11) Sv Bq(-1), 25-50% lower than the median probabilistic values. The tritium oxide dose conversion factor model was found to be most sensitive to biological half-life and quality factor and is highly dependent on the standardizing radiation for RBE assessments.

Adult↗
PubMed1981

Sensitivity of health endpoints: effect on conclusions of studies.

The types of biological response to an environmental agent can depend on dose, thus in this case a family of widely different dose-response relationships would be expected. For those situations where the magnitude of the effect may be determined on probabilistic grounds as a function of dose ("stochastic" model), no particular dose-response relationship-may necessarily be inferred; the appropriate model still depends on the biological processes under consideration. Some examples of different conclusions concerning dose-response are given for studies of effects of lead and carbon monoxide at low doses. With increasingly sensitive measures of physiologic responses, these can be detected at exposures close to background, but for many cases the question remains whether an observed response really represents a true toxic effect. The application of epidemiologic data for regulatory purposes may depend on identification of the response to an agent appropriate for preventive measures. The conclusions one reaches about studies of health effects of environmental agents can be markedly influenced by the types of health endpoints under consideration.

Air Pollutants↗
PubMed1993

Violations of transitivity: Implications for a theory of contextual choice.

Violations of strong stochastic transitivity in concurrent-chains choice were first reported by Navarick and Fantino. In a series of articles, Navarick and Fantino concluded that neither a unidimensional model capable of predicting exact choice probabilities nor a fixed-variable equivalence rule was possible for the concurrent-chains procedure. I show that when choice is modeled contextually (i.e., when preference for a schedule is affected by factors other than the schedule itself, e.g., aspects of the alternative schedule), a unidimensional, exact-choice probability model is possible that both predicts the intransitivities reported by Navarick and Fantino and provides a fixed-variable equivalence rule for the concurrent-chains procedure. The contextual model is an extension of the generalized matching law and violates a key assumption underlying traditional choice models-simple scalability-because of (a) schedule interdependence and (b) bias from procedural contingencies. Therefore, strong stochastic transitivity cannot be expected to hold. Contextual scalability is analyzed to reveal a hierarchy of context effects in choice. Navarick and Fantino's intransitivities can be satisfactorily explained by bias. If attribute sensitivity is context dependent, however, and if there are similarity structures among choice alternatives, the contextual model is shown to be able to predict violations of ordinal preference. Therefore, it may be possible to formulate a deterministic, general psychophysical model of choice as a behavioral alternative to probabilistic, multidimensional choice theories.

Journal Article↗
PubMed2003

Convergence properties of three spike-triggered analysis techniques.

We analyse the convergence properties of three spike-triggered data analysis techniques. Our results are obtained in the setting of a probabilistic linear-nonlinear (LN) cascade neural encoding model; this model has recently become popular in the study of the neural coding of natural signals. We start by giving exact rate-of-convergence results for the common spike-triggered average technique. Next, we analyse a spike-triggered covariance method, variants of which have been recently exploited successfully by Bialek, Simoncelli and colleagues. Unfortunately, the conditions that guarantee that these two estimators will converge to the correct parameters are typically not satisfied by natural signal data. Therefore, we introduce an estimator for the LN model parameters which is designed to converge under general conditions to the correct model. We derive the rate of convergence of this estimator, provide an algorithm for its computation and demonstrate its application to simulated data as well as physiological data from the primary motor cortex of awake behaving monkeys. We also give lower bounds on the convergence rate of any possible LN estimator. Our results should prove useful in the study of the neural coding of high-dimensional natural signals.

Action Potentials↗
PubMed2004

Biologically valid linear factor models of gene expression.

MOTIVATION: The identification of physiological processes underlying and generating the expression pattern observed in microarray experiments is a major challenge. Principal component analysis (PCA) is a linear multivariate statistical method that is regularly employed for that purpose as it provides a reduced-dimensional representation for subsequent study of possible biological processes responding to the particular experimental conditions. Making explicit the data assumptions underlying PCA highlights their lack of biological validity thus making biological interpretation of the principal components problematic. A microarray data representation which enables clear biological interpretation is a desirable analysis tool. RESULTS: We address this issue by employing the probabilistic interpretation of PCA and proposing alternative linear factor models which are based on refined biological assumptions. A practical study on two well-understood microarray datasets highlights the weakness of PCA and the greater biological interpretability of the linear models we have developed.

Algorithms↗