Use of Hy's law and a new composite algorithm to predict acute liver failure in patients with drug-induced liver injury.

BACKGROUND & AIMS Hy's Law, which states that hepatocellular drug-induced liver injury (DILI) with jaundice indicates a serious reaction, is used widely to determine risk for acute liver failure (ALF). We aimed to optimize the definition of Hy's Law and to develop a model for predicting ALF in patients with DILI. METHODS We collected data from 771 patients with DILI (805 episodes) from the Spanish DILI registry, from April 1994 through August 2012. We analyzed data collected at DILI recognition and at the time of peak levels of alanine aminotransferase (ALT) and total bilirubin (TBL). RESULTS Of the 771 patients with DILI, 32 developed ALF. Hepatocellular injury, female sex, high levels of TBL, and a high ratio of aspartate aminotransferase (AST):ALT were independent risk factors for ALF. We compared 3 ways to use Hy's Law to predict which patients would develop ALF; all included TBL greater than 2-fold the upper limit of normal (×ULN) and either ALT level greater than 3 × ULN, a ratio (R) value (ALT × ULN/alkaline phosphatase × ULN) of 5 or greater, or a new ratio (nR) value (ALT or AST, whichever produced the highest ×ULN/ alkaline phosphatase × ULN value) of 5 or greater. At recognition of DILI, the R- and nR-based models identified patients who developed ALF with 67% and 63% specificity, respectively, whereas use of only ALT level identified them with 44% specificity. However, the level of ALT and the nR model each identified patients who developed ALF with 90% sensitivity, whereas the R criteria identified them with 83% sensitivity. An equal number of patients who did and did not develop ALF had alkaline phosphatase levels greater than 2 × ULN. An algorithm based on AST level greater than 17.3 × ULN, TBL greater than 6.6 × ULN, and AST:ALT greater than 1.5 identified patients who developed ALF with 82% specificity and 80% sensitivity. CONCLUSIONS When applied at DILI recognition, the nR criteria for Hy's Law provides the best balance of sensitivity and specificity whereas our new composite algorithm provides additional specificity in predicting the ultimate development of ALF.

Materials nanocomposits a partir de whiskers de cel•lulosa i matriu polimèrica de cautxú

De acuerdo con los objetivos generales del proyecto y plan de trabajo previsto, para esta anualidad, se obtuvieron fibras y microfibras de celulosa a partir de dos fuentes: celulosa vegetal de pino y eucalipto y celulosa bacterial. Las microfibrillas han sido utilizadas como material de refuerzo para la fabricación de materiales compuestos a partir de caucho natural, policaprolactona y polivinil alcohol. Las muestras se fabricaron mediante la técnica de "casting" en medio acuoso y temperatura ambiente. Las muestras fueron caracterizados en sus propiedades mecánicas, físicas y térmicas. Se observó que, en general, la adición de las microfibrillas de celulosa en las matrices poliméricas provoca una mejora sustancial en las propiedades mecánicas del material en comparación con el polímero sin reforzar. Los resultados pueden resumirse de la siguiente manera: 1.Fabricación de materiales compuestos a base de caucho natural y fibras de celulosa. Se obtuvieron fibras y nanofibras de celulosa que fueron modificadas químicamente y usadas como refuerzo en matriz de caucho. Los resultados mostraron mejora de propiedades mecánicas del material, principalmente en los materiales compuestos reforzados con nanofibras. 2. Obtención de whiskers de celulosa y su utilización como material de refuerzo en una matriz de policaprolactona. Se obtuvieron whiskers de celulosa a partir de pasta blanqueada. La adición en una matriz de policaprolactona produjo materiales compuestos con propiedades mecánicas superiores a la matriz, con buena dispersión de los whiskers. 3. Obtención de fibras de celulosa bacterial y nanofibras de celulosa, aislamiento y utilización sobre una matriz de polivinil alcohol. Se obtuvo celulosa bacterial a partir de la bacteria Gluconacetobacter xylinum. Además se fabricaron nanofibras de celulosa a partir eucalipto blanqueado. La celulosa bacterial como material de refuerzo no produjo importantes mejoras en las propiedades mecánicas de la matriz; en cambio se observaron mejoras destacables con la nanofibra como refuerzo.

Role of Particle Shape on the Stress Propagation in Granular Packings

We present an experimental and numerical study on the influence that particle aspect ratio has on the mechanical and structural properties of granular packings. For grains with maximal symmetry (squares), the stress propagation in the packing localizes forming chainlike forces analogous to the ones observed for spherical grains. This scenario can be understood in terms of stochastic models of aggregation and random multiplicative processes. As the grains elongate, the stress propagation is strongly affected. The interparticle normal force distribution tends toward a Gaussian, and, correspondingly, the force chains spread leading to a more uniform stress distribution reminiscent of the hydrostatic profiles known for standard liquids

Probabilistic evidential assessment of gunshot residue particle evidence (Part II) : Bayesian parameter estimation for experimental count data.

Part I of this series of articles focused on the construction of graphical probabilistic inference procedures, at various levels of detail, for assessing the evidential value of gunshot residue (GSR) particle evidence. The proposed models - in the form of Bayesian networks - address the issues of background presence of GSR particles, analytical performance (i.e., the efficiency of evidence searching and analysis procedures) and contamination. The use and practical implementation of Bayesian networks for case pre-assessment is also discussed. This paper, Part II, concentrates on Bayesian parameter estimation. This topic complements Part I in that it offers means for producing estimates useable for the numerical specification of the proposed probabilistic graphical models. Bayesian estimation procedures are given a primary focus of attention because they allow the scientist to combine (his/her) prior knowledge about the problem of interest with newly acquired experimental data. The present paper also considers further topics such as the sensitivity of the likelihood ratio due to uncertainty in parameters and the study of likelihood ratio values obtained for members of particular populations (e.g., individuals with or without exposure to GSR).

Evaluation of Composite Pavement Unbonded Overlays: Phases I and II, April 2003

In recent years, thin whitetopping has evolved as a viable rehabilitation technique for deteriorated asphalt cement concrete (ACC) pavements. Numerous projects have been constructed and tested; these projects allow researchers to identify the important elements contributing to the projects’ successes. These elements include surface preparation, overlay thickness, synthetic fiber reinforcement usage, joint spacing, and joint sealing. Although the main factors affecting thin whitetopping performance have been identified by previous research, questions still existed as to the optimum design incorporating these variables. The objective of this research is to investigate the interaction between these variables over time. Laboratory testing and field-testing were planned in order to accomplish the research objective. Laboratory testing involved shear testing of the bond between the portland cement concrete (PCC) overlay and the ACC surface. Field-testing involved falling weight deflectometer deflection responses, measurement of joint faulting and joint opening, and visual distress surveys on the 9.6-mile project. The project was located on Iowa Highway 13 extending north from the city of Manchester, Iowa, to Iowa Highway 3 in Delaware County. Variables investigated included ACC surface preparation, PCC thickness, synthetic fiber reinforcement usage, and joint spacing. This report documents the planning, equipment selection, construction, field changes, and construction concerns of the project built in 2002. The data from this research could be combined with historical data to develop a design specification for the construction of thin, unbonded overlays.

Causal explanations and scientific realism in particle physics

Particle physics studies highly complex processes which cannot be directly observed. Scientific realism claims that we are nevertheless warranted in believing that these processes really occur and that the objects involved in them really exist. This dissertation defends a version of scientific realism, called causal realism, in the context of particle physics. I start by introducing the central theses and arguments in the recent philosophical debate on scientific realism (chapter 1), with a special focus on an important presupposition of the debate, namely common sense realism. Chapter 2 then discusses entity realism, which introduces a crucial element into the debate by emphasizing the importance of experiments in defending scientific realism. Most of the chapter is concerned with Ian Hacking's position, but I also argue that Nancy Cartwright's version of entity realism is ultimately preferable as a basis for further development. In chapter 3,1 take a step back and consider the question whether the realism debate is worth pursuing at all. Arthur Fine has given a negative answer to that question, proposing his natural ontologica! attitude as an alternative to both realism and antirealism. I argue that the debate (in particular the realist side of it) is in fact less vicious than Fine presents it. The second part of my work (chapters 4-6) develops, illustrates and defends causal realism. The key idea is that inference to the best explanation is reliable in some cases, but not in others. Chapter 4 characterizes the difference between these two kinds of cases in terms of three criteria which distinguish causal from theoretical warrant. In order to flesh out this distinction, chapter 5 then applies it to a concrete case from the history of particle physics, the discovery of the neutrino. This case study shows that the distinction between causal and theoretical warrant is crucial for understanding what it means to "directly detect" a new particle. But the distinction is also an effective tool against what I take to be the presently most powerful objection to scientific realism: Kyle Stanford's argument from unconceived alternatives. I respond to this argument in chapter 6, and I illustrate my response with a discussion of Jean Perrin's experimental work concerning the atomic hypothesis. In the final part of the dissertation, I turn to the specific challenges posed to realism by quantum theories. One of these challenges comes from the experimental violations of Bell's inequalities, which indicate a failure of locality in the quantum domain. I show in chapter 7 how causal realism can further our understanding of quantum non-locality by taking account of some recent experimental results. Another challenge to realism in quantum mechanics comes from delayed-choice experiments, which seem to imply that certain aspects of what happens in an experiment can be influenced by later choices of the experimenter. Chapter 8 analyzes these experiments and argues that they do not warrant the antirealist conclusions which some commentators draw from them. It pays particular attention to the case of delayed-choice entanglement swapping and the corresponding question whether entanglement is a real physical relation. In chapter 9,1 finally address relativistic quantum theories. It is often claimed that these theories are incompatible with a particle ontology, and this calls into question causal realism's commitment to localizable and countable entities. I defend the commitments of causal realism against these objections, and I conclude with some remarks connecting the interpretation of quantum field theory to more general metaphysical issues confronting causal realism.

[Recueil composite].

Contient : Job, cum commentariis ; Fridegisus, Tractatus de grammatica (34-36). - S. Bonifatius, Ars grammatica (36v-47v, 58-70). - Tatuinus, Ars grammatica (48, 57, 49-56v, 79-86, 71-78v)

Evaluation of Composite Pavement Unbonded Overlays: Phase III, August 2006

In recent years, thin whitetopping has evolved as a viable rehabilitation technique for deteriorated asphalt cement concrete (ACC) pavements. Numerous projects have been constructed and tested, allowing researchers to identify the important elements contributing to the projects’ successes. These elements include surface preparation, overlay thickness, synthetic fiber reinforcement usage, joint spacing, and joint sealing. Although the main factors affecting thin whitetopping performance have been identified by previous research, questions still existed as to the optimum design incorporating these variables. The objective of this research is to investigate the interaction between these variables over time. Laboratory testing and field testing were conducted to achieve the research objectives. Laboratory testing involved shear testing of the bond between the portland cement concrete (PCC) overlay and the ACC surface. Field testing involved falling weight deflectometer deflection responses, measurement of joint faulting and joint opening, and visual distress surveys on the 9.6-mile project. The project was located on Iowa Highway 13 extending north from the city of Manchester, Iowa, to Iowa Highway 3 in Delaware County. Variables investigated include ACC surface preparation, PCC thickness, slab size, synthetic fiber reinforcement usage, and joint spacing. This report documents the planning, construction, and performance of each variable in the time period from summer 2002 through spring 2006. The project has performed well with only minor distress identification since its construction.

An assessment of empirical Bayes and composite estimators for small areas

We compare a set of empirical Bayes and composite estimators of the population means of the districts (small areas) of a country, and show that the natural modelling strategy of searching for a well fitting empirical Bayes model and using it for estimation of the area-level means can be inefficient.

Using composite estimators to improve both domain and total area estimation

In this article we propose using small area estimators to improve the estimatesof both the small and large area parameters. When the objective is to estimateparameters at both levels accurately, optimality is achieved by a mixed sampledesign of fixed and proportional allocations. In the mixed sample design, oncea sample size has been determined, one fraction of it is distributedproportionally among the different small areas while the rest is evenlydistributed among them. We use Monte Carlo simulations to assess theperformance of the direct estimator and two composite covariant-freesmall area estimators, for different sample sizes and different sampledistributions. Performance is measured in terms of Mean Squared Errors(MSE) of both small and large area parameters. It is found that the adoptionof small area composite estimators open the possibility of 1) reducingsample size when precision is given, or 2) improving precision for a givensample size.

Rate of convergence of a particle method to the solution of the Mc Kean-Vlasov's equation

This paper studies the rate of convergence of an appropriatediscretization scheme of the solution of the Mc Kean-Vlasovequation introduced by Bossy and Talay. More specifically,we consider approximations of the distribution and of thedensity of the solution of the stochastic differentialequation associated to the Mc Kean - Vlasov equation. Thescheme adopted here is a mixed one: Euler/weakly interactingparticle system. If $n$ is the number of weakly interactingparticles and $h$ is the uniform step in the timediscretization, we prove that the rate of convergence of thedistribution functions of the approximating sequence in the $L^1(\Omega\times \Bbb R)$ norm and in the sup norm is of theorder of $\frac 1{\sqrt n} + h $, while for the densities is ofthe order $ h +\frac 1 {\sqrt {nh}}$. This result is obtainedby carefully employing techniques of Malliavin Calculus.