Joint Modelling in Liver Transplantation

In the setting of liver transplantation, clinical trials and transplant registries regularly collect repeated measurements of clinical biomarkers which may be strongly associated with a time-to-event such as graft failure or disease recurrence. Multiple time-to-event outcomes are routinely collected. However, joint models are rarely used. This thesis will describe important considerations for joint modelling in the setting of liver transplantation. We will focus on transplant registry data from the United States. We develop a new tool for joint modelling in the context where a critical health event can be tracked in the longitudinal biomarker and often presents as a non-linear trajectory with a sharp jump. We capture this non-linearity with a sin- gle change-point longitudinal component that is linked to the survival model via random effects in a way that incorporates the size of this change, which is a novel way to use a sharp change in the subject-specific random effect as a linkage in a joint model. We also propose an alternative to time dependent analysis of treatment effects by using a joint survival outcome model with a time-to-drug-failure event and a terminal event in graft failure that is more appropriate to use in drug effectiveness studies where subjects are discontinued from an immunosuppressant (in favour of alternative treatment) due to health reasons. Modelling drug regime failures as a time-to-event process has not been previously considered in transplant studies. We show that this method shows a significant association of time-to-drug-failure with time-to-graft-failure, whether applied with a longitudinal component or on its own in a joint survival outcome model

Genetic and Physiological Characterisation of Oenococcus oeni Strains to Perform Malolactic Fermentation in Wines

Malolactic fermentation (MLF) is a process that is increasingly conducted by Oenococcus oeni industrial strains.Recently, studies of the diversity of O. oeni strains have developed some potential genetic tools to characterise theabilities of the strains. During this work, a mutation on a partial sequence of the rpoB gene and the presence ofsome genes previously established to be present in the most performing strains were tested on some strains thatare already marketed and some potential new strains. These tests were compared with a physiological test neverpreviously taken into account: the tolerance to octanoic and decanoic acid, important inhibitory compounds in wines.Our objectives were to compare the relevance of the genetic tests currently available, that of resistance to mediumchain fatty acids and the results of winemaking. Ultimately, it is clear that, as far as current knowledge is concerned,genetic tests are not yet sufficient to completely characterise the strain potential, and physiological tests thereforeare always needed. The resistance to medium chain fatty acids is an interesting point to be considered to explain thedifficulty that some strains have to resist inoculation in wine. But other criteria should also be characterised better,such as the duration of the latent phase between inoculation and the beginning of MLF, and the rate of degradationof malic acid by the different strains

Relevance of visco-plastic theory in a multi-directional inhomogeneous granular flow

We confront a recent visco-plastic description of dense granular flows [P. Jop et al, Nature, {\bf 441} (2006) 727] with multi-directional inhomogeneous steady flows observed in non-smooth contact dynamics simulations of 2D half-filled rotating drums. Special attention is paid to check separately the two underlying fundamental statements into which the considered theory can be recast, namely (i) a single relation between the invariants of stress and strain rate tensors and (ii) the alignment between these tensors. Interestingly, the first prediction is fairly well verified over more than four decades of small strain rate, from the surface rapid flow to the quasi-static creep phase, where it is usually believed to fail because of jamming. On the other hand, the alignment between stress and strain rate tensors is shown to fail over the whole flow, what yields an apparent violation of the visco-plastic rheology when applied without care. In the quasi-static phase, the particularly large misalignment is conjectured to be related to transient dilatancy effects

The S shape of a granular pile in a rotating drum

The shape of a granular pile in a rotating drum is investigated. Using Discrete Elements Method (DEM) simulations we show that the "S shape" obtained for high rotation speed can be accounted for by the friction on the end plates. A theoretical model which accounts for the effect of the end plates is presented and the equation of the shape of the free surface is derived. The model reveals a dimensionless number which quantifies the influence of the end plates on the shape of the pile. Finally, the scaling laws of the system are discussed and numerical results support our conclusions

Changes in Grape Maturity Induced by Spraying Ethanol

Three different ethanol solutions were sprayed onto Cabernet Sauvignon (Vitis vinifera L.) clusters during the ripening period: 2.5, 5 and 10% by volume in water. Controls were sprayed with water alone. Three different times of spraying were also tested: 8, 10 and 13 weeks post-flowering. One of the observed changes was a lower titratable acidity in grape samples at harvest, when the clusters were sprayed with ethanol at 10 weeks, in comparison with controls. The wines made with grapes treated with ethanol after mid-veraison, had higher ODs at 520 nm than did the controls. This may due to a combined effect of red pigment levels and acidity. In addition, following malolactic fermentation, the acidity levels of wines made with ethanoltreated grapes were slightly higher than those made with the control grapes. Spraying ethanol at 13 weeks post-flowering increased the berry weight by 10% at harvest without decreasing the °Brix value. The corresponding wines had similar degrees of alcohol. This observation was made for the first time in 2001

Numerical simulation of 2D steady granular flows in rotating drum: On surface flows rheology

13 pages, 14 figures, 61 references, submitted to Phys. FluidsThe rheology of 2D steady surface flow of cohesionless cylinders in a rotating drum is investigated through {\em Non Smooth Contact Dynamics} simulations. Profile of volume fraction, translational and angular velocity, rms velocity, strain rate and stress tensor were measured at the midpoint along the length of the surface flowing layer where the flow is generally considered as steady and homogeneous. Analysis of these data and their inter-relations suggest the local inertial number - defined as the ratio between local inertial forces and local confinement forces - to be the relevant dimensionless parameter to describe the transition from the quasi-static part of the packing to the flowing part at the surface of the heap. Variations of the components of the stress tensor as well as the ones of rms velocity as a function of the inertial number are analysed within both the quasi-static and the flowing phases. Their implications are discussed

Yeasts and wine off-flavours: a technological perspective

Review article. Part of the special issue "Wine microbiology and safety: from the vineyard to the bottle (Microsafety Wine)", 19-20 Nov. 2009, ItalyIn wine production, yeasts have both beneficial and detrimental activities. Saccharomyces cerevisiae is the yeast mainly responsible for turning grape juice into wine but this species and several others may also show undesirable effects in wines. Among such effects, technologists are particularly concerned with the production of offflavours that may occur during all stages of winemaking. Typical spoiling activities include the production of ethyl acetate by apiculate yeasts before fermentation, hydrogen sulphide by S. cerevisiae during fermentation phases, acetaldehyde by film-forming yeasts during bulk storage, and volatile phenols by Dekkera bruxellensis during storage or after bottling. The occurrence of these hazards depends on the technological operations designed to obtain a given type of wine and most can be avoided by current preventive or curative measures. On the contrary, good manufacturing practices must be strengthened to deal with the problem of volatile phenol production in red wines. Appropriate monitoring of D. bruxellensis populations and quantification of 4-ethylphenol is advised during storage, particularly when oak barrels are used, and absence of viable cells must be guaranteed in bottled wines. This work, which is based on our experience at winery level, aims to provide information on appropriate technological strategies to deal with the problem of off-flavours produced by yeasts