Browse ORBi by ORBi project

- Background
- Content
- Benefits and challenges
- Legal aspects
- Functions and services
- Team
- Help and tutorials

Bayesian P-spline estimation in hierarchical models specified by systems of affine differential equations Jaeger, Jonathan ; Lambert, Philippe in Statistical Modelling : An International Journal (2013), 13 Ordinary differential equations (ODEs) are widely used to model physical, chemical and biological processes. Current methods for parameter estimation can be computationally intensive and/or not suitable ... [more ▼] Ordinary differential equations (ODEs) are widely used to model physical, chemical and biological processes. Current methods for parameter estimation can be computationally intensive and/or not suitable for inference and prediction. Frequentist approaches based on ODE-penalized smoothing techniques have recently solved part of these drawbacks. A full Bayesian approach based on ODE-penalized B-splines is proposed to jointly estimate ODE parameters and state functions from affine systems of differential equations. Simulations inspired by pharmacokinetic studies show that the proposed method provides comparable results to methods based on explicit solution of the ODEs and outperforms the frequentist ODE-penalized smoothing approach. The basic model is extended to a hierarchical one in order to study cases where several subjects are involved. This Bayesian hierarchical approach is illustrated on real data for the study of perfusion ratio after a femoral artery occlusion. Model selection is feasible through the analysis of the posterior distributions of the ODE adhesion parameters and is illustrated on a real pharmacokinetic dataset. [less ▲] Detailed reference viewed: 46 (13 ULg)A Bayesian Design Space for analytical methods based on multivariate models and predictions Lebrun, Pierre ; Boulanger, Bruno ; Debrus, Benjamin et al in Journal of Biopharmaceutical Statistics (2013), 23 The International Conference for Harmonization (ICH) has released regulatory guidelines for Pharmaceutical Development. In the document ICH Q8, The Design Space of a process is presented as the set of ... [more ▼] The International Conference for Harmonization (ICH) has released regulatory guidelines for Pharmaceutical Development. In the document ICH Q8, The Design Space of a process is presented as the set of factor settings providing satisfactory results. However, ICH Q8 does not propose any practical methodology to define, derive and compute Design Space. In parallel, in the last decades, it has been observed that the diversity and the quality of analytical methods have evolved exponentially allowing substantial gains in selectivity and sensitivity. However, there is still a lack for a rationale towards the development of robust separation methods in a systematic way. Applying ICH Q8 to analytical methods provides a methodology for predicting a region of the space of factors in which results will be reliable. Combining design of experiments and Bayesian standard multivariate regression, an identified form of the predictive distribution of a new response vector has been identified and used, under non-informative as well as informative prior distributions of the parameters. From the responses and their predictive distribution, various critical quality attributes can be easily derived. This Bayesian framework was then extended to the multi-criteria setting to estimate the predictive probability that several critical quality attributes will be jointly achieved in the future use of an analytical method. An example based on a high-performance liquid chromatography (HPLC) method is given. For this example, a constrained sampling scheme was applied to ensure the modeled responses have desirable properties. [less ▲] Detailed reference viewed: 253 (64 ULg)Nonparametric additive location-scale models for interval censored data Lambert, Philippe in Statistics and computing (2013), 23 An nonparametric additive model for the location and dispersion of a continuous response with an arbitrary smooth conditional distribution is proposed. B-splines are used to specify the three components ... [more ▼] An nonparametric additive model for the location and dispersion of a continuous response with an arbitrary smooth conditional distribution is proposed. B-splines are used to specify the three components of the model. It can deal with interval censored data and multiple covariates. After a simulation study, the relation between age, the number of years of full-time education and the net income (provided as intervals) available per person in Belgian households is studied from survey data. [less ▲] Detailed reference viewed: 59 (12 ULg)Bayesian ODE-penalized B-spline model with Gaussian mixture as error distribution Jaeger, Jonathan ; Lambert, Philippe Scientific conference (2012, July 18) In the standard Bayesian ODE-penalized B-spline approach, it is assumed that the error distribution is homogeneous Gaussian. But, in many applications, the normal assumption for the error distribution is ... [more ▼] In the standard Bayesian ODE-penalized B-spline approach, it is assumed that the error distribution is homogeneous Gaussian. But, in many applications, the normal assumption for the error distribution is not a realistic choice. The goal of this paper is to extend the standard Bayesian ODE-penalized B-spline approach to settings where the error term distribution can be described using a mixture of normals. [less ▲] Detailed reference viewed: 25 (2 ULg)On the use of adhesion parameters to validate models specified using systems of affine differential equations Jaeger, Jonathan ; Lambert, Philippe E-print/Working paper (2012) A strategy for the selection of system of differential equations is proposed based on Bayesian ODE-penalized B-spline approach. It estimates the ODE parameters, approximates the solution of the ODE model ... [more ▼] A strategy for the selection of system of differential equations is proposed based on Bayesian ODE-penalized B-spline approach. It estimates the ODE parameters, approximates the solution of the ODE model and quantifies the suitability of the proposed differential equations to model the dynamics of the observed state functions. Simulation study confirms that these ODE-adhesion parameters are able to question a system of differential equations as a descriptor of the dynamics in the state functions. This methodology is illustrated on a pharmacokinetic study. [less ▲] Detailed reference viewed: 22 (2 ULg)Testing conditional asymmetry: a residual-based approach Lambert, Philippe ; ; in Journal of Economic Dynamics & Control (2012), 36 We propose three residual-based tests for conditional asymmetry. The distribution is assumed to fall into the class of skewed distributions of Fernandez and Steel (1998). In this class, asymmetry is ... [more ▼] We propose three residual-based tests for conditional asymmetry. The distribution is assumed to fall into the class of skewed distributions of Fernandez and Steel (1998). In this class, asymmetry is measured by the ratio between the probabilities of being larger and smaller than the mode. Estimation is performed under the null hypothesis of constant asymmetry of the innovations and, in a second step, tests for conditional asymmetry are performed on generalized residuals through parametric and non- parametric methods. We derive the asymptotic distribution of the tests that incorporates the uncertainty of the estimated parameters. A Monte Carlo study shows that neglecting this uncertainty severely biases the tests. An empirical application on a basket of daily returns reveals that financial data often present dynamics in the conditional skewness. [less ▲] Detailed reference viewed: 15 (3 ULg)Efficacy of pre-ascent climbing route visual inspection in indoor sport climbing ; Lambert, Philippe ; et al in Scandinavian Journal of Medicine & Science in Sports (2012), 22 Pre-ascent climbing route visual inspection (route preview) has been suggested as a key climbing performance para- meter although its role has never been verified experimentally. We examined the efficacy ... [more ▼] Pre-ascent climbing route visual inspection (route preview) has been suggested as a key climbing performance para- meter although its role has never been verified experimentally. We examined the efficacy of this perceptual-cognitive skill on indoor sport climbing performance. Twenty-nine male climbers, divided into intermediate, advanced and expert climbing level groups, climbed two indoor sport routes matching their climbing level and, where applicable, routes below their climbing level. At each level, one route was climbed with a preview, where participants benefited from a 3-min pre-ascent climbing route visual inspection. Performance was assessed in terms of output (route comple- tion) and form (number and duration of moves and stops). Route preview did not influence the output performance. Climbers using visual inspection were no more likely to finish the ascent than those without the option of using visual inspection. Conversely, route preview did influence form performance; climbers made fewer, and shorter stops during their ascent following a preview of the route. Form performances differences remained when baseline ability levels were taken into account, although for shorter duration of stops only with expert climbers benefiting most from route preview. The ability to visually inspect a climb before its ascent may represent an essential component of performance optimization. [less ▲] Detailed reference viewed: 90 (4 ULg)Smooth estimation of survival functions and hazard ratios from interval-censored data using Bayesian penalized B-splines Cetinyürek, Aysun ; Lambert, Philippe in Statistics in Medicine (2011), 30(1), 75-90 We discuss the use of Bayesian P-spline and of the composite link model to estimate survival functions and hazard-ratios from interval-censored data. If one further assumes proportionality of the hazards ... [more ▼] We discuss the use of Bayesian P-spline and of the composite link model to estimate survival functions and hazard-ratios from interval-censored data. If one further assumes proportionality of the hazards, the proposed strategy provides a smoothed estimate of the baseline hazard along with estimates of global covariate effects. The frequentist properties of our Bayesian estimators are assessed by an extensive simulation study. We further illustrate the methodology by two examples showing that the proportionality of the hazards might also be found inappropriate from interval-censored data. [less ▲] Detailed reference viewed: 33 (13 ULg)Comments on: Inference in multivariate Archimedean copulas models Lambert, Philippe in Test (2011), 20 Detailed reference viewed: 26 (0 ULg)Health insurance coverage and adverse selection Lambert, Philippe ; Perelman, Sergio ; Pestieau, Pierre et al in Börsch-Supan, Axel; Brandt, Martina; Hank, Karsten (Eds.) et al The Individual and the Welfare State: Life Histories in Europe (2011) Detailed reference viewed: 53 (9 ULg)Smooth semiparametric and nonparametric Bayesian estimation of bivariate densities from bivariate histogram data Lambert, Philippe in Computational Statistics & Data Analysis (2011), 55 Penalized B-splines combined with the composite link model are used to estimate a bivariate density from a histogram with wide bins. The goals are multiple: they include the visualization of the ... [more ▼] Penalized B-splines combined with the composite link model are used to estimate a bivariate density from a histogram with wide bins. The goals are multiple: they include the visualization of the dependence between the two variates, but also the estimation of derived quantities like Kendall’s tau, conditional moments and quantiles. Two strategies are proposed: the first one is semiparametric with flexible margins modeled using B-splines and a parametric copula for the dependence structure; the second one is nonparametric and is based on Kronecker products of the marginal B-spline bases. Frequentist and Bayesian estimations are described. A large simulation study quantifies the performances of the two methods under different dependence structures and for varying strengths of dependence, sample sizes and amounts of grouping. It suggests that Schwarz’s BIC is a good tool for classifying the competing models. The density estimates are used to evaluate conditional quantiles in two applications in social and in medical sciences. [less ▲] Detailed reference viewed: 41 (6 ULg)Developing and optimizing analytical chromatographic method in a Quality by Design environment. Bayesian multi-criteria risk-based Design Space to guarantee future quality. Lebrun, Pierre ; Lambert, Philippe ; Debrus, Benjamin et al Poster (2010, December) Detailed reference viewed: 78 (10 ULg)Use of Bayesian multivariate prediction models to optimize chromatographic methods Lebrun, Pierre ; Boulanger, Bruno ; Lambert, Philippe Conference (2010, May) Detailed reference viewed: 30 (8 ULg)Adaptive Bayesian P-splines to estimate varying regression coeﬃcients: application to receptor occupancy estimation ; Lambert, Philippe ; in JSM Proceedings, Statistical Computing Section. Alexandria, VA: American Statistical Association. (2009) In many applications of linear regression models, the regression coeﬃcients are not regarded as ﬁxed but as varying with another covariate named the eﬀect modiﬁer. A useful extension of the linear ... [more ▼] In many applications of linear regression models, the regression coeﬃcients are not regarded as ﬁxed but as varying with another covariate named the eﬀect modiﬁer. A useful extension of the linear regression models are then varying coeﬃcient models. To link the regression coeﬃcient with the eﬀect modiﬁer, several methods may be considered. Here, we propose to use Bayesian P-splines to relate in a smoothed way the regression coeﬃcient with the eﬀect modiﬁer. We show that this method enables a large level of ﬂexibility: if necessary, adaptive penalties can be introduced in the model (Jullion and Lambert 2007) and linear constraints on the relation between the regression coeﬃcient and the eﬀect modiﬁer may easily be added. We provide an illustration of the proposed method in a PET study where we want to estimate the relation between the Receptor Occupancy and the drug concentration in the plasma. As we work in a Bayesian setting, credibility sets are easily obtained for receptor occupancy, which take into account the uncertainty appearing at all the diﬀerent estimation steps. [less ▲] Detailed reference viewed: 75 (13 ULg)Pharmacokinetic parameters estimation using adaptive Bayesian P-splines models ; Lambert, Philippe ; et al in Pharmaceutical Statistics (2009), 8 In preclinical and clinical experiments, pharmacokinetic (PK) studies are designed to analyse the evolution of drug concentration in plasma over time i.e. the PK profile. Some PK parameters are estimated ... [more ▼] In preclinical and clinical experiments, pharmacokinetic (PK) studies are designed to analyse the evolution of drug concentration in plasma over time i.e. the PK profile. Some PK parameters are estimated in order to summarize the complete drug’s kinetic profile: area under the curve (AUC), maximal concentration (Cmax), time at which the maximal concentration occurs (tmax) and half-life time (t1/2). Several methods have been proposed to estimate these PK parameters. A first method relies on interpolating between observed concentrations. The interpolation method is often chosen linear. This method is simple and fast. Another method relies on compartmental modelling. In this case, nonlinear methods are used to estimate parameters of a chosen compartmental model. This method provides generally good results. However, if the data are sparse and noisy, two difficulties can arise with this method. The first one is related to the choice of the suitable compartmental model given the small number of data available in preclinical experiment for instance. Second, nonlinear methods can fail to converge. Much work has been done recently to circumvent these problems (J. Pharmacokinet. Pharmacodyn. 2007; 34:229–249, Stat. Comput., to appear, Biometrical J., to appear, ESAIM P&S 2004; 8:115–131). In this paper, we propose a Bayesian nonparametric model based on P-splines. This method provides good PK parameters estimation, whatever be the number of available observations and the level of noise in the data. Simulations show that the proposed method provides better PK parameters estimations than the interpolation method, both in terms of bias and precision. The Bayesian nonparametric method provides also better AUC and t1/2 estimations than a correctly specified compartmental model, whereas this last method performs better in tmax and Cmax estimations. We extend the basic model to a hierarchical one that treats the case where we have concentrations from different subjects. We are then able to get individual PK parameter estimations. Finally, with Bayesian methods, we can get easily some uncertainty measures by obtaining credibility sets for each PK parameter. [less ▲] Detailed reference viewed: 77 (8 ULg)Bayesian density estimation from grouped continuous data Lambert, Philippe ; in Computational Statistics & Data Analysis (2009), 53 Grouped data occur frequently in practice, either because of limited resolution of instruments, or because data have been summarized in relatively wide bins. A combination of the composite link model with ... [more ▼] Grouped data occur frequently in practice, either because of limited resolution of instruments, or because data have been summarized in relatively wide bins. A combination of the composite link model with roughness penalties is proposed to estimate smooth densities from such data in a Bayesian framework. A simulation study is used to evaluate the performances of the strategy in the estimation of a density, of its quantiles and rst moments. Two illustrations are presented: the rst one involves grouped data of lead concentrations in the blood and the second one the number of deaths due to tuberculosis in The Netherlands in wide age classes. [less ▲] Detailed reference viewed: 32 (10 ULg)Set up of a serum-free culture system for bovine embryos: embryo development and quality before and after transient transfer ; ; et al in Theriogenology (2008), 69 It is well known that serum in culture medium negatively affects blastocyst quality. The objective of this work was to develop and test a serum-free culture medium which could improve embryo quality ... [more ▼] It is well known that serum in culture medium negatively affects blastocyst quality. The objective of this work was to develop and test a serum-free culture medium which could improve embryo quality, measured by the resistance to freezing, lipid and glutathione content of the resulting blastocysts, as well as the ability of the blastocysts to elongate after transient transfer to recipient cows. In a first experiment we showed that adding a mixture of insulin, transferrin and selenium to serum-free Synthetic Oviduct Fluid medium (SOF–ITS) improved embryo development and quality. In the second experiment, the addition of BSA to SOF–ITS further improved blastocyst development. Moreover, a reduction in lipid content of morulae was observed in SOF–ITS–BSA by comparison with morulae cultured with serum (SOF–FCS). The resistance to freezing measured by hatching rates 24 h postthawing was also improved for blastocysts with a diameter between 160 and 180 mm cultured in SOF–ITS–BSA by comparison to those produced with serum. In order to evaluate the redox potential of the embryos, reduced glutathione content (GSH) was evaluated both before and after cryopreservation. A significant decrease in glutathione was observed after freezing, whatever the culture medium, but no difference was observed between culture conditions. Transient transfers were performed and elongated D- 13 embryos were recovered. Elongation was more pronounced and the embryonic disk more often visible in embryos cultured in SOF–ITS–BSA than in embryos cultured with FCS. In conclusion, the serum-free system we developed to produce in vitro bovine embryos meets the developmental and qualitative requirements for a large-scale use. [less ▲] Detailed reference viewed: 31 (4 ULg)Archimedean copula estimation using Bayesian splines smoothing techniques Lambert, Philippe in Computational Statistics & Data Analysis (2007), 51(12), 6307-6320 Copulas enable to specify multivariate distributions with given marginals. Various parametric proposals were made in the literature for these quantities, mainly in the bivariate case. They can be ... [more ▼] Copulas enable to specify multivariate distributions with given marginals. Various parametric proposals were made in the literature for these quantities, mainly in the bivariate case. They can be systematically derived from multivariate distributions with known marginals, yielding e.g. the normal and the Student copulas. Alternatively, one can restrict his/her interest to a sub-family of copulas named Archimedean. They are characterized by a strictly decreasing convex function on (0, 1) which tends to +infinity at 0 (when strict) and which is 0 at 1. A ratio approximation of the generator and of its first derivative using B-splines is proposed and the associated parameters estimated using Markov chains Monte Carlo methods. The estimation is reasonably quick. The fitted generator is smooth and parametric. The generated chain(s) can be used to build "credible envelopes" for the above ratio function and derived quantities such as Kendall's tau, posterior predictive probabilities, etc. Parameters associated to parametric models for the marginals can be estimated jointly with the copula parameters. This is an interesting alternative to the popular two-step procedure which assumes that the regression parameters are fixed known quantities when it comes to copula parameter(s) estimation. A simulation study is performed to evaluate the approach. The practical utility of the method is illustrated by a basic analysis of the dependence structure underlying the diastolic and the systolic blood pressures in male subjects. (C) 2007 Elsevier B.V. All rights reserved. [less ▲] Detailed reference viewed: 41 (5 ULg)Greatest accuracy credibility with dynamic heterogeneity: the Harvey-Fernandes model ; ; et al in Belgian Actuarial Bulletin (2007), 7(1), 14-18 This paper proposes a generalization of the merit rating system described in Dionne & Vanasse (1989,1992). The model takes into account explanatory variables as well as possible modifications in the ... [more ▼] This paper proposes a generalization of the merit rating system described in Dionne & Vanasse (1989,1992). The model takes into account explanatory variables as well as possible modifications in the policyholders unobservable risk characteristics. It is based on the analysis of time series for count observations proposed by Harvey & Fernandes (1989). Numerical results obtained with a Spanish panel databasis for motor insurance illustrate the approach described in this paper. [less ▲] Detailed reference viewed: 15 (2 ULg)Effect of a collaborative approach on the quality of prescribing for geriatric inpatients: a randomized controlled trial ; ; et al in Journal of the American Geriatrics Society (2007), 55(5), 658-665 OBJECTIVES: To evaluate the effect of pharmaceutical care provided in addition to acute Geriatric Evaluation and Management (GEM) care on the appropriateness of prescribing. DESIGN: Randomized, controlled ... [more ▼] OBJECTIVES: To evaluate the effect of pharmaceutical care provided in addition to acute Geriatric Evaluation and Management (GEM) care on the appropriateness of prescribing. DESIGN: Randomized, controlled trial, with the patient as unit of randomization. SETTING: Acute GEM unit. PARTICIPANTS: Two hundred three patients aged 70 and older. INTERVENTION: Pharmaceutical care provided from admission to discharge by a specialist clinical pharmacist who had direct contacts with the GEM team and patients. MEASUREMENTS: Appropriateness of prescribing on admission, at discharge, and 3 months after discharge, using the Medication Appropriateness Index (MAI), Beers criteria, and Assessing Care of Vulnerable Elders (ACOVE) underuse criteria and mortality, readmission, and emergency visits up to 12 months after discharge. RESULTS: Intervention patients were significantly more likely than control patients to have an improvement in the MAI and in the ACOVE underuse criteria from admission to discharge (odds ratio (OR)=9.1, 95% confidence interval (CI)=4.2-21.6 and OR=6.1, 95% CI=2.2-17.0, respectively). The control and intervention groups had comparable improvements in the Beers criteria. CONCLUSION: Pharmaceutical care provided in the context of acute GEM care improved the appropriate use of medicines during the hospital stay and after discharge. This is an important finding, because only limited data exist on the effect of various strategies to improve medication use in elderly inpatients. The present approach has the potential to minimize risk and improve patient outcomes. [less ▲] Detailed reference viewed: 81 (12 ULg) |
||