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See detailSet up of a serum-free culture system for bovine embryos: embryo development and quality before and after transient transfer
George, F.; Daniaux, C.; Génicot, G. 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 ▲]

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See detailArchimedean copula estimation using Bayesian splines smoothing techniques
Lambert, Philippe ULg

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 ▲]

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See detailEffect of a collaborative approach on the quality of prescribing for geriatric inpatients: a randomized controlled trial
Spinewine, A.; Swine, C.; Dhillon, S. 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 ▲]

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See detailComparison between principal component analysis and independent component analysis in EEG modelling
Bugli, Céline; Lambert, Philippe ULg

in Biometrical Journal = Biometrische Zeitschrift (2007), 49

Principal Component Analysis (PCA) is a classical technique in statistical data analysis, feature extraction and data reduction, aiming at explaining observed signals as a linear combination of orthogonal ... [more ▼]

Principal Component Analysis (PCA) is a classical technique in statistical data analysis, feature extraction and data reduction, aiming at explaining observed signals as a linear combination of orthogonal principal components. Independent Component Analysis (ICA) is a technique of array processing and data analysis, aiming at recovering unobserved signals or ‘sources’ from observed mixtures, exploiting only the assumption of mutual independence between the signals. The separation of the sources by ICA has great potential in applications such as the separation of sound signals (like voices mixed in simultaneous multiple records, for example), in telecommunication or in the treatment of medical signals. However, ICA is not yet often used by statisticians. In this paper, we shall present ICA in a statistical framework and compare this method with PCA for electroencephalograms (EEG) analysis.We shall see that ICA provides a more useful data representation than PCA, for instance, for the representation of a particular characteristic of the EEG named event-related potential (ERP). [less ▲]

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See detailRobust specification of the roughness penalty prior distribution in spatially adaptive Bayesian P-splines models
Jullion, Astrid; Lambert, Philippe ULg

in Computational Statistics & Data Analysis (2007), 51

The potential important role of the prior distribution of the roughness penalty parameter in the resulting smoothness of Bayesian Psplines models is considered. The recommended specification for that ... [more ▼]

The potential important role of the prior distribution of the roughness penalty parameter in the resulting smoothness of Bayesian Psplines models is considered. The recommended specification for that distribution yields models that can lack flexibility in specific circumstances. In such instances, these are shown to correspond to a frequentist P-splines model with a predefined and severe roughness penalty parameter, an obviously undesirable feature. It is shown that the specification of a hyperprior distribution for one parameter of that prior distribution provides the desired flexibility. Alternatively, a mixture prior can also be used. An extension of these two models by enabling adaptive penalties is provided. The posterior of all the proposed models can be quickly explored using the convenient Gibbs sampler. [less ▲]

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See detailFunctional ANOVA with random functional effects: an application to event-related potentials modelling for electroencephalograms analysis
Bugli, Céline; Lambert, Philippe ULg

in Statistics in Medicine (2006), 25

The di erential e ects of basic visual or auditory stimuli on electroencephalograms (EEG), named event related potentials (ERPs), are often used to evaluate the impact of treatments on brain performances ... [more ▼]

The di erential e ects of basic visual or auditory stimuli on electroencephalograms (EEG), named event related potentials (ERPs), are often used to evaluate the impact of treatments on brain performances. In the present paper, we propose a P-splines based model that can be used to evaluate treatment e ect on the timing and the amplitude of some peaks of the ERPs curves. Functional ANOVA is an adaptation of linear model or analysis of variance to analyse functional observations. The changes in the functional of interest e ects are generally described using smoothing splines. Eilers and Marx proposed to work with P-splines, a combination of B-splines and di erence penalties on coe cients. We de ne a Psplines model for ERPs curves combined with random e ects. In particular, we show that it is a useful alternative to classical strategies requiring the visual and usually imprecise localization of speci c ERP peaks from curves with a low signal-to-noise ratio. [less ▲]

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See detailDiscrimination of shifts in a soil microbial community assosciated with TNT-contamination using a functional ANOVA of 16S rRNA hybridized to oligonucleotide microarrays
Eyers; Smoot, J. C.; Smoot, L. M. et al

in Environmental Science & Technology (2006), 40

A functional ANOVA analysis of the thermal dissociation of RNA hybridized to DNA microarrays was used to improve discrimination between two soil microbial communities. Following hybridization of in vitro ... [more ▼]

A functional ANOVA analysis of the thermal dissociation of RNA hybridized to DNA microarrays was used to improve discrimination between two soil microbial communities. Following hybridization of in vitro transcribed 16S rRNA derived from uncontaminated and 2,4,6- trinitrotoluene contaminated soils to an oligonucleotide microarray containing group- and species-specific perfect match (PM) probes and mismatch (MM) variants, thermal dissociation was used to analyze the nucleic acid bound to each PM-MM probe set. Functional ANOVA of the dissociation curves generally discriminated PM-MM probe sets when Td values (temperature at 50% probe-target dissociation) could not. Maximum discrimination for many PM and MM probes often occurred at temperatures greater than theTd. Comparison of signal intensities measured prior to dissociation analysis from hybridizations of the two soil samples revealed significant differences in domain-, group-, and species-specific probes. Functional ANOVA showed significantly different dissociation curves for 11 PM probes when hybridizations from the two soil samples were compared, even though initial signal intensities for 3 of the 11 did not vary. [less ▲]

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See detailConstraints on concordance measures in bivariate discrete data
Denuit, Michel; Lambert, Philippe ULg

in Journal of Multivariate Analysis (2005), 93

This paper aims to investigate the constraints on dependence measures based on the concept of concordance when discrete random variables are involved. The main technical argument consists in a continuous ... [more ▼]

This paper aims to investigate the constraints on dependence measures based on the concept of concordance when discrete random variables are involved. The main technical argument consists in a continuous extension of integer-valued random variables by convolution with unit support kernels [less ▲]

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See detailLocal dependence estimation using semi-parametric Archimedean copulas
Vandenhende, François; Lambert, Philippe ULg

in Canadian Journal of Statistics = Revue Canadienne de Statistique (2005), 33

The authors de¯ne a new semiparametric Archimedean copula family having a °exible depen- dence structure. The family's generator is a local interpolation of existing generators. It has locally-de¯ned ... [more ▼]

The authors de¯ne a new semiparametric Archimedean copula family having a °exible depen- dence structure. The family's generator is a local interpolation of existing generators. It has locally-de¯ned dependence parameters. The authors present a penalized constrained least-squares method to estimate and smooth these parameters. They illustrate the °exibility of their dependence model in a bivariate survival example. [less ▲]

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See detailffects of oligofructose on glucose and lipid metabolism in patients with nonalcoholic steatohepatitis : results of a pilot study
Daubioul, C. A.; Horsmans, Y.; Lambert, Philippe ULg et al

in European Journal of Clinical Nutrition (2005), 59

Objective: In experimental animals, recent results suggest that the addition of inulin-type fructans such as oligofructose (OFS) in the diet decreases triacylglycerol accumulation in the liver tissue ... [more ▼]

Objective: In experimental animals, recent results suggest that the addition of inulin-type fructans such as oligofructose (OFS) in the diet decreases triacylglycerol accumulation in the liver tissue. Therefore, we have investigated the effect of daily ingestion of OFS in seven patients with nonalcoholic steatohepatitis (NASH), confirmed by liver biopsies. Design: They received 16 g/day OFS or maltodextrine (placebo) for 8 weeks in a randomized double-blind crossover design. Energy intake, body composition, liver steatosis and blood parameters were analysed after 4 and 8 weeks of dietary supplementation. Results: Compared to placebo, OFS decreased significantly serum aminotransferases, aspartate aminotransferase after 8 weeks, and insulin level after 4 weeks, but this could not be related to significant effect on plasma lipids. Conclusion: This pilot study supports the putative interest of OFS in the management of liver diseases associated with abnormal lipid accumulation in humans. [less ▲]

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See detailBayesian proportional hazards model with time varying regression coefficients: a penalized Poisson regression approach
Lambert, Philippe ULg; Eilers, Paul H.C.

in Statistics in Medicine (2005), 24

One can fruitfully approach survival problems without covariates in an actuarial way. In narrow time bins, the number of people at risk is counted together with the number of events. The relationship ... [more ▼]

One can fruitfully approach survival problems without covariates in an actuarial way. In narrow time bins, the number of people at risk is counted together with the number of events. The relationship between time and probability of an event can then be estimated with a parametric or semi-parametric model. The number of events observed in each bin is described using a Poisson distribution with the log mean speci ed using a exible penalized B-splines model with a large number of equidistant knots. Regression on pertinent covariates can easily be performed using the same log-linear model, leading to the classical proportional hazard model. We propose to extend that model by allowing the regression coe cients to vary in a smooth way with time. Penalized B-splines models will be proposed for each of these coe cients. We show how the regression parameters and the penalty weights can be estimated e ciently using Bayesian inference tools based on the Metropolis-adjusted Langevin algorithm. [less ▲]

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See detailParametric accelerated failure time models with random effects and an application to kidney transplant survival
Lambert, Philippe ULg; Collett, Dave; Kimber, Alan et al

in Statistics in Medicine (2004), 23

Accelerated failure time models with a shared random component are described, and are used to evaluate the effect of explanatory factors and different transplant centres on survival times following kidney ... [more ▼]

Accelerated failure time models with a shared random component are described, and are used to evaluate the effect of explanatory factors and different transplant centres on survival times following kidney transplantation. Different combinations of the distribution of the random effects and baseline hazard function are considered and the fit of such models to the transplant data is critically assessed. A mixture model that combines short- and long-term components of a hazard function is then developed, which provides a more flexible model for the hazard function. The model can incorporate different explanatory variables and random effects in each component. The model is straightforward to fit using standard statistical software, and is shown to be a good fit to the transplant data. [less ▲]

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See detailStatistical models for the analysis of controlled trials on acute migraine
Vandenhende, François; Lambert, Philippe ULg

in Pharmaceutical Statistics (2003), 2

pecific efficacy criteria were defined by the International Headache Society for controlled clinical trials on acute migraine. They are derived from the pain profile and the timing of rescue medication ... [more ▼]

pecific efficacy criteria were defined by the International Headache Society for controlled clinical trials on acute migraine. They are derived from the pain profile and the timing of rescue medication intake. We present a methodology to improve the analysis of such trials. Instead of analysing each endpoint separately, we model the joint distribution and derive success rates in any criteria as predictions. We use cumulative regression models for each response at a time and a multivariate normal copula to model the dependence between responses. Parameters are estimated using maximum likelihood. Benefits of the method include a reduction in the number of tests performed and an increase in their power. The method is well suited to dose-response trials from which predictions can be used to select doses and optimize the design of subsequent trials. More generally, our method permits a very flexible modelling of longitudinal series of ordinal data. [less ▲]

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See detailGeneralized Pareto fit to the Society of Actuaries large claims database
Cebrian, Ana; Denuit, Michel; Lambert, Philippe ULg

in North American Actuarial Journal (2003), 7

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See detailImproved rank-based dependence measures for categorical data
Vandenhende, François; Lambert, Philippe ULg

in Statistics & Probability Letters (2003), 63

We extend rank-based dependence measures like Spearman's rho to categorical data so that the same ±1 limits are always reached under complete dependence. A goodness-of-fit procedure is derived for ... [more ▼]

We extend rank-based dependence measures like Spearman's rho to categorical data so that the same ±1 limits are always reached under complete dependence. A goodness-of-fit procedure is derived for dependence models using copulas. [less ▲]

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See detailAnalysis of bivariate tail dependence using extreme values copulas: An application to the SOA medical large claims database
Cebrian, Ana; Denuit, Michel; Lambert, Philippe ULg

in Belgian Actuarial Journal (2003)

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See detailA mixture model to assess the effect of a hormonal stimulation on the development of follicles in prepubertal heifers
Lambert, Philippe ULg

in Journal of the Royal Statistical Society : Series C (Applied Statistics) (2002), 4

The goal of this study is to assess the effect of follicle stimulating hormone (FSH) on the growth of follicles in prepubertal heifers. Adams and co-workers have shown that follicles develop in waves as ... [more ▼]

The goal of this study is to assess the effect of follicle stimulating hormone (FSH) on the growth of follicles in prepubertal heifers. Adams and co-workers have shown that follicles develop in waves as in post-pubertal heifers: after a few days, a dominant follicle arises on one of the two ovaries whereas the other subordinate follicles regress.The dominant follicle remains detectable when the next wave occurs. The number and the diameters of these follicles have been measured for 14 days.The same experiment was repeated after a 3-day FSH stimulation. Several large follicles now arise simultaneously on both ovaries together with small follicles which cannot be detected any more when the next wave occurs. Unfortunately, follicles were not individually tracked. Therefore a three-component mixture model was used to describe the potential simultaneous observation of dominant, decaying dominant and subordinate follicles before the FSH stimulation; the same type of model was considered for large, decaying large and small follicles after the hormonal stimulation. Moreover, for technical reasons, only follicles larger than 2 mm are observable. Measurements were thus left truncated.The models fitted are used to quantify the effects of the stimulation and to determine the ideal time point at which follicles should be punctured under ultrasonography to harvest ovocytes that will be fertilized and cultured in vitro. [less ▲]

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See detailA copula based model for multivariate non normal longitudinal data: analysis of a dose titration safety study on a new antidepressant
Lambert, Philippe ULg; Vandenhende, François

in Statistics in Medicine (2002), 21

A new model for multivariate non-normal longitudinal data is proposed. In a first step, each longitudinal series of data corresponding to a given response is modelled separately using a copula to relate ... [more ▼]

A new model for multivariate non-normal longitudinal data is proposed. In a first step, each longitudinal series of data corresponding to a given response is modelled separately using a copula to relate the marginal distributions of the response at each time of observation. In a second step, at each observation time, the conditional (on the past) distributions of each response are related using another copula describing the relationship between the corresponding variables. Note that there is no need to consider the same family of distributions for these response variables. The technique is illustrated in a dose titration safety study on a new antidepressant. The haemodynamic effect on diastolic blood pressure, systolic blood pressure and heart rate is studied. These three responses are measured repeatedly over time on ten healthy volunteers during the dose escalation. The available covariates are sex and the concentration of drug in the plasma at time of measurement. [less ▲]

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See detailOn the joint analysis of longitudinal responses and early discontinuation in randomized trials
Vandenhende, François; Lambert, Philippe ULg

in Journal of Biopharmaceutical Statistics (2002), 12

Our focus is on the joint analysis of longitudinal nonnormal responses and early discontinuation in (pre)-clinical trials. Separate models are fitted to the two series (response and discontinuation) to ... [more ▼]

Our focus is on the joint analysis of longitudinal nonnormal responses and early discontinuation in (pre)-clinical trials. Separate models are fitted to the two series (response and discontinuation) to account for covariate and time effects. The serial dependence and the dependence between response and drop-out are also modeled. This is done using particular dependence functions, called copulas. Copulas are used to create a joint distribution with given marginal distributions. Applications are given for the analysis of heart rate/morbidity in toxicology and pain severity/intake of rescue medications in a trial on migraine. Using copulas, the level of dependence between two variables remains invariant to changes in the marginal distribution of either variable. This proves interesting in modeling the association in a longitudinal setting when responses change over time. [less ▲]

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See detailEffect of conventional controlled-rate freezing and vitrification on quality of bovine blasotcysts produced in vitro
Kaidi, Safia; Bernard, S.; Lambert, Philippe ULg et al

in Biology of Reproduction (2001), 65

This study compares the effects of conventional controlled-rate freezing and vitrification on the morphology and metabolism of in vitro-produced bovine blastocysts. Day 7 expanded blastocysts cultured in ... [more ▼]

This study compares the effects of conventional controlled-rate freezing and vitrification on the morphology and metabolism of in vitro-produced bovine blastocysts. Day 7 expanded blastocysts cultured in synthetic oviduct fluid with 5% fetal calf serum were frozen in 1.36 M glycerol, 0.25 M sucrose or vitrified in 25% glycerol, 25% ethylene glycol. Cell alterations and in vitro development were evaluated immediately after thawing or after 72 h. The effect of cryopreservation on inner cell mass and trophectoderm (TE) cell number as well as glucose, pyruvate, and oxygen uptakes, and lactate release by blastocysts were evaluated. Immediately after thawing, blastocysts showed equivalent cell membrane permeabilization after both cryopreservation procedures, while alterations in nuclear staining were more frequent in vitrified embryos. After culture, similar survival and hatching rates were observed. Both procedures decreased cell number immediately after thawing and after 72 h. However, the number of TE cells was lower in frozen embryos than in vitrified ones. In relation to this, frozen blastocysts showed a decrease in glucose, pyruvate, and oxygen uptake, although those parameters were not altered in vitrified embryos. An increased glycolytic activity was also observed in frozen embryos, indicating a stress response to this procedure. [less ▲]

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