Development of a population-based cost-effectiveness model of chronic graft versus host disease in Spain

Chronic graft-versus-host disease (cGvHD) is the leading cause of late nonrelapse mortality (transplant-related mortality) after hematopoietic stem cell transplant. Given that there are a wide range of treatment options for cGvHD, assessment of the associated costs and efficacy can help clinicians and health care providers allocate health care resources more efficiently. OBJECTIVE: The purpose of this study was to assess the cost-effectiveness of extracorporeal photopheresis (ECP) compared with rituximab (Rmb) and with imatinib (Imt) in patients with cGvHD at 5 years from the perspective of the Spanish National Health System. METHODS: The model assessed the incremental cost-effectiveness/utility ratio of ECP versus Rmb or Imt for 1000 hypothetical patients by using microsimulation cost-effectiveness techniques. Model probabilities were obtained from the literature. Treatment pathways and adverse events were evaluated taking clinical opinion and published reports into consideration. Local data on costs (2010 Euros) and health care resources utilization were validated by the clinical authors. Probabilistic sensitivity analyses were used to assess the robustness of the model. RESULTS: The greater efficacy of ECP resulted in a gain of 0.011 to 0.024 quality-adjusted life-year in the first year and 0.062 to 0.094 at year 5 compared with Rmb or Imt. The results showed that the higher acquisition cost of ECP versus Imt was compensated for at 9 months by greater efficacy; this higher cost was partially compensated for ( 517) by year 5 versus Rmb. After 9 months, ECP was dominant (cheaper and more effective) compared with Imt. The incremental cost-effectiveness ratio of ECP versus Rmb was 29,646 per life-year gained and 24,442 per quality-adjusted life-year gained at year 2.5. Probabilistic sensitivity analysis confirmed the results. The main study limitation was that to assess relative treatment effects, only small studies were available for indirect comparison. CONCLUSION: ECP as a third-line therapy for cGvHD is a more cost-effective strategy than Rmb or Imt.

Reflexive Space. A Constructionist Model of the Russian Reflexive Marker

This study examines the structure of the Russian Reflexive Marker ( ся/-сь) and offers a usage-based model building on Construction Grammar and a probabilistic view of linguistic structure. Traditionally, reflexive verbs are accounted for relative to non-reflexive verbs. These accounts assume that linguistic structures emerge as pairs. Furthermore, these accounts assume directionality where the semantics and structure of a reflexive verb can be derived from the non-reflexive verb. However, this directionality does not necessarily hold diachronically. Additionally, the semantics and the patterns associated with a particular reflexive verb are not always shared with the non-reflexive verb. Thus, a model is proposed that can accommodate the traditional pairs as well as for the possible deviations without postulating different systems. A random sample of 2000 instances marked with the Reflexive Marker was extracted from the Russian National Corpus and the sample used in this study contains 819 unique reflexive verbs. This study moves away from the traditional pair account and introduces the concept of Neighbor Verb. A neighbor verb exists for a reflexive verb if they share the same phonological form excluding the Reflexive Marker. It is claimed here that the Reflexive Marker constitutes a system in Russian and the relation between the reflexive and neighbor verbs constitutes a cross-paradigmatic relation. Furthermore, the relation between the reflexive and the neighbor verb is argued to be of symbolic connectivity rather than directionality. Effectively, the relation holding between particular instantiations can vary. The theoretical basis of the present study builds on this assumption. Several new variables are examined in order to systematically model variability of this symbolic connectivity, specifically the degree and strength of connectivity between items. In usage-based models, the lexicon does not constitute an unstructured list of items. Instead, items are assumed to be interconnected in a network. This interconnectedness is defined as Neighborhood in this study. Additionally, each verb carves its own niche within the Neighborhood and this interconnectedness is modeled through rhyme verbs constituting the degree of connectivity of a particular verb in the lexicon. The second component of the degree of connectivity concerns the status of a particular verb relative to its rhyme verbs. The connectivity within the neighborhood of a particular verb varies and this variability is quantified by using the Levenshtein distance. The second property of the lexical network is the strength of connectivity between items. Frequency of use has been one of the primary variables in functional linguistics used to probe this. In addition, a new variable called Constructional Entropy is introduced in this study building on information theory. It is a quantification of the amount of information carried by a particular reflexive verb in one or more argument constructions. The results of the lexical connectivity indicate that the reflexive verbs have statistically greater neighborhood distances than the neighbor verbs. This distributional property can be used to motivate the traditional observation that the reflexive verbs tend to have idiosyncratic properties. A set of argument constructions, generalizations over usage patterns, are proposed for the reflexive verbs in this study. In addition to the variables associated with the lexical connectivity, a number of variables proposed in the literature are explored and used as predictors in the model. The second part of this study introduces the use of a machine learning algorithm called Random Forests. The performance of the model indicates that it is capable, up to a degree, of disambiguating the proposed argument construction types of the Russian Reflexive Marker. Additionally, a global ranking of the predictors used in the model is offered. Finally, most construction grammars assume that argument construction form a network structure. A new method is proposed that establishes generalization over the argument constructions referred to as Linking Construction. In sum, this study explores the structural properties of the Russian Reflexive Marker and a new model is set forth that can accommodate both the traditional pairs and potential deviations from it in a principled manner.

Analysis of applicability of Peleg model to the cooking-infusion of mackerel (Scomber japonicus) slices

Mass transfer kinetics in osmotic dehydration is usually modeled by Fick's law, empirical models and probabilistic models. The aim of this study was to determine the applicability of Peleg model to investigate the mass transfer during osmotic dehydration of mackerel (Scomber japonicus) slices at different temperatures. Osmotic dehydration was performed on mackerel slices by cooking-infusion in solutions with glycerol and salt (a w = 0.64) at different temperatures: 50, 70, and 90 ºC. Peleg rate constant (K1) (h(g/gdm)-1) varied with temperature variation from 0.761 to 0.396 for water loss, from 5.260 to 2.947 for salt gain, and from 0.854 to 0.566 for glycerol intake. In all cases, it followed the Arrhenius relationship (R²>0.86). The Ea (kJ / mol) values obtained were 16.14; 14.21, and 10.12 for water, salt, and glycerol, respectively. The statistical parameters that qualify the goodness of fit (R²>0.91 and RMSE<0.086) indicate promising applicability of Peleg model.

Suppression of long-branch attraction artefacts in the animal phylogeny using a site-heterogeneous model

Affiliation: Département de Biochimie, Université de Montréal

Macroemesures in Computable General Equilibrium Models: a Probabilistic Treatment with an Application to Morocco.

With the help of an illustrative general equilibrium (CGE) model of the Moroccan Economy, we test for the significance of simulation results in the case where the exact macromesure is not known with certainty. This is done by computing lower and upper bounds for the simulation resukts, given a priori probabilities attached to three possible closures (Classical, Johansen, Keynesian). Our Conclusion is that, when there is uncertainty on closures several endogenous changes lack significance, which, in turn, limit the use of the model for policy prescriptions.

A Statistical Image-Based Shape Model for Visual Hull Reconstruction and 3D Structure Inference

We present a statistical image-based shape + structure model for Bayesian visual hull reconstruction and 3D structure inference. The 3D shape of a class of objects is represented by sets of contours from silhouette views simultaneously observed from multiple calibrated cameras. Bayesian reconstructions of new shapes are then estimated using a prior density constructed with a mixture model and probabilistic principal components analysis. We show how the use of a class-specific prior in a visual hull reconstruction can reduce the effect of segmentation errors from the silhouette extraction process. The proposed method is applied to a data set of pedestrian images, and improvements in the approximate 3D models under various noise conditions are shown. We further augment the shape model to incorporate structural features of interest; unknown structural parameters for a novel set of contours are then inferred via the Bayesian reconstruction process. Model matching and parameter inference are done entirely in the image domain and require no explicit 3D construction. Our shape model enables accurate estimation of structure despite segmentation errors or missing views in the input silhouettes, and works even with only a single input view. Using a data set of thousands of pedestrian images generated from a synthetic model, we can accurately infer the 3D locations of 19 joints on the body based on observed silhouette contours from real images.

Probabilistic Independence Networks for Hidden Markov Probability Models

Graphical techniques for modeling the dependencies of randomvariables have been explored in a variety of different areas includingstatistics, statistical physics, artificial intelligence, speech recognition, image processing, and genetics.Formalisms for manipulating these models have been developedrelatively independently in these research communities. In this paper weexplore hidden Markov models (HMMs) and related structures within the general framework of probabilistic independencenetworks (PINs). The paper contains a self-contained review of the basic principles of PINs.It is shown that the well-known forward-backward (F-B) and Viterbialgorithms for HMMs are special cases of more general inference algorithms forarbitrary PINs. Furthermore, the existence of inference and estimationalgorithms for more general graphical models provides a set of analysistools for HMM practitioners who wish to explore a richer class of HMMstructures.Examples of relatively complex models to handle sensorfusion and coarticulationin speech recognitionare introduced and treated within the graphical model framework toillustrate the advantages of the general approach.

Probabilistic models to assist maintenance of multiple instruments

The paper discusses maintenance challenges of organisations with a huge number of devices and proposes the use of probabilistic models to assist monitoring and maintenance planning. The proposal assumes connectivity of instruments to report relevant features for monitoring. Also, the existence of enough historical registers with diagnosed breakdowns is required to make probabilistic models reliable and useful for predictive maintenance strategies based on them. Regular Markov models based on estimated failure and repair rates are proposed to calculate the availability of the instruments and Dynamic Bayesian Networks are proposed to model cause-effect relationships to trigger predictive maintenance services based on the influence between observed features and previously documented diagnostics

Parameter sensitivity and predictive uncertainty in a new water quality model, Q(2)

A new dynamic model of water quality, Q(2), has recently been developed, capable of simulating large branched river systems. This paper describes the application of a generalized sensitivity analysis (GSA) to Q(2) for single reaches of the River Thames in southern England. Focusing on the simulation of dissolved oxygen (DO) (since this may be regarded as a proxy for the overall health of a river); the GSA is used to identify key parameters controlling model behavior and provide a probabilistic procedure for model calibration. It is shown that, in the River Thames at least, it is more important to obtain high quality forcing functions than to obtain improved parameter estimates once approximate values have been estimated. Furthermore, there is a need to ensure reasonable simulation of a range of water quality determinands, since a focus only on DO increases predictive uncertainty in the DO simulations. The Q(2) model has been applied here to the River Thames, but it has a broad utility for evaluating other systems in Europe and around the world.

Probabilistic simulations of crop yield over western India using the DEMETER seasonal hindcast ensembles

Process-based integrated modelling of weather and crop yield over large areas is becoming an important research topic. The production of the DEMETER ensemble hindcasts of weather allows this work to be carried out in a probabilistic framework. In this study, ensembles of crop yield (groundnut, Arachis hypogaea L.) were produced for 10 2.5 degrees x 2.5 degrees grid cells in western India using the DEMETER ensembles and the general large-area model (GLAM) for annual crops. Four key issues are addressed by this study. First, crop model calibration methods for use with weather ensemble data are assessed. Calibration using yield ensembles was more successful than calibration using reanalysis data (the European Centre for Medium-Range Weather Forecasts 40-yr reanalysis, ERA40). Secondly, the potential for probabilistic forecasting of crop failure is examined. The hindcasts show skill in the prediction of crop failure, with more severe failures being more predictable. Thirdly, the use of yield ensemble means to predict interannual variability in crop yield is examined and their skill assessed relative to baseline simulations using ERA40. The accuracy of multi-model yield ensemble means is equal to or greater than the accuracy using ERA40. Fourthly, the impact of two key uncertainties, sowing window and spatial scale, is briefly examined. The impact of uncertainty in the sowing window is greater with ERA40 than with the multi-model yield ensemble mean. Subgrid heterogeneity affects model accuracy: where correlations are low on the grid scale, they may be significantly positive on the subgrid scale. The implications of the results of this study for yield forecasting on seasonal time-scales are as follows. (i) There is the potential for probabilistic forecasting of crop failure (defined by a threshold yield value); forecasting of yield terciles shows less potential. (ii) Any improvement in the skill of climate models has the potential to translate into improved deterministic yield prediction. (iii) Whilst model input uncertainties are important, uncertainty in the sowing window may not require specific modelling. The implications of the results of this study for yield forecasting on multidecadal (climate change) time-scales are as follows. (i) The skill in the ensemble mean suggests that the perturbation, within uncertainty bounds, of crop and climate parameters, could potentially average out some of the errors associated with mean yield prediction. (ii) For a given technology trend, decadal fluctuations in the yield-gap parameter used by GLAM may be relatively small, implying some predictability on those time-scales.

Evaluation of probabilistic occupancy map people detection for surveillance systems

In this paper, we evaluate the Probabilistic Occupancy Map (POM) pedestrian detection algorithm on the PETS 2009 benchmark dataset. POM is a multi-camera generative detection method, which estimates ground plane occupancy from multiple background subtraction views. Occupancy probabilities are iteratively estimated by fitting a synthetic model of the background subtraction to the binary foreground motion. Furthermore, we test the integration of this algorithm into a larger framework designed for understanding human activities in real environments. We demonstrate accurate detection and localization on the PETS dataset, despite suboptimal calibration and foreground motion segmentation input.

A forward constrained selection algorithm for probabilistic neural network

A new probabilistic neural network (PNN) learning algorithm based on forward constrained selection (PNN-FCS) is proposed. An incremental learning scheme is adopted such that at each step, new neurons, one for each class, are selected from the training samples arid the weights of the neurons are estimated so as to minimize the overall misclassification error rate. In this manner, only the most significant training samples are used as the neurons. It is shown by simulation that the resultant networks of PNN-FCS have good classification performance compared to other types of classifiers, but much smaller model sizes than conventional PNN.

Early warning with calibrated and sharper probabilistic forecasts

Given a nonlinear model, a probabilistic forecast may be obtained by Monte Carlo simulations. At a given forecast horizon, Monte Carlo simulations yield sets of discrete forecasts, which can be converted to density forecasts. The resulting density forecasts will inevitably be downgraded by model mis-specification. In order to enhance the quality of the density forecasts, one can mix them with the unconditional density. This paper examines the value of combining conditional density forecasts with the unconditional density. The findings have positive implications for issuing early warnings in different disciplines including economics and meteorology, but UK inflation forecasts are considered as an example.

Regularized logistic models for probabilistic forecasting and diagnostics

Logistic models are studied as a tool to convert dynamical forecast information (deterministic and ensemble) into probability forecasts. A logistic model is obtained by setting the logarithmic odds ratio equal to a linear combination of the inputs. As with any statistical model, logistic models will suffer from overfitting if the number of inputs is comparable to the number of forecast instances. Computational approaches to avoid overfitting by regularization are discussed, and efficient techniques for model assessment and selection are presented. A logit version of the lasso (originally a linear regression technique), is discussed. In lasso models, less important inputs are identified and the corresponding coefficient is set to zero, providing an efficient and automatic model reduction procedure. For the same reason, lasso models are particularly appealing for diagnostic purposes.

Reliability of regional climate model trends

A necessary condition for a good probabilistic forecast is that the forecast system is shown to be reliable: forecast probabilities should equal observed probabilities verified over a large number of cases. As climate change trends are now emerging from the natural variability, we can apply this concept to climate predictions and compute the reliability of simulated local and regional temperature and precipitation trends (1950–2011) in a recent multi-model ensemble of climate model simulations prepared for the Intergovernmental Panel on Climate Change (IPCC) fifth assessment report (AR5). With only a single verification time, the verification is over the spatial dimension. The local temperature trends appear to be reliable. However, when the global mean climate response is factored out, the ensemble is overconfident: the observed trend is outside the range of modelled trends in many more regions than would be expected by the model estimate of natural variability and model spread. Precipitation trends are overconfident for all trend definitions. This implies that for near-term local climate forecasts the CMIP5 ensemble cannot simply be used as a reliable probabilistic forecast.