Classification models for neurocognitive impairment in HIV infection based on demographic and clinical variables

Objective: We used demographic and clinical data to design practical classification models for prediction of neurocognitive impairment (NCI) in people with HIV infection. Methods: The study population comprised 331 HIV-infected patients with available demographic, clinical, and neurocognitive data collected using a comprehensive battery of neuropsychological tests. Classification and regression trees (CART) were developed to btain detailed and reliable models to predict NCI. Following a practical clinical approach, NCI was considered the main variable for study outcomes, and analyses were performed separately in treatment-naïve and treatment-experienced patients. Results: The study sample comprised 52 treatment-naïve and 279 experienced patients. In the first group, the variables identified as better predictors of NCI were CD4 cell count and age (correct classification [CC]: 79.6%, 3 final nodes). In treatment-experienced patients, the variables most closely related to NCI were years of education, nadir CD4 cell count, central nervous system penetration-effectiveness score, age, employment status, and confounding comorbidities (CC: 82.1%, 7 final nodes). In patients with an undetectable viral load and no comorbidities, we obtained a fairly accurate model in which the main variables were nadir CD4 cell count, current CD4 cell count, time on current treatment, and past highest viral load (CC: 88%, 6 final nodes). Conclusion: Practical classification models to predict NCI in HIV infection can be obtained using demographic and clinical variables. An approach based on CART analyses may facilitate screening for HIV-associated neurocognitive disorders and complement clinical information about risk and protective factors for NCI in HIV-infected patients.

Evaluation of drug-induced neurotoxicity based on metabolomics, proteomics and electrical activity measurements in complementary CNS in vitro models.

The present study was performed in an attempt to develop an in vitro integrated testing strategy (ITS) to evaluate drug-induced neurotoxicity. A number of endpoints were analyzed using two complementary brain cell culture models and an in vitro blood-brain barrier (BBB) model after single and repeated exposure treatments with selected drugs that covered the major biological, pharmacological and neuro-toxicological responses. Furthermore, four drugs (diazepam, cyclosporine A, chlorpromazine and amiodarone) were tested more in depth as representatives of different classes of neurotoxicants, inducing toxicity through different pathways of toxicity. The developed in vitro BBB model allowed detection of toxic effects at the level of BBB and evaluation of drug transport through the barrier for predicting free brain concentrations of the studied drugs. The measurement of neuronal electrical activity was found to be a sensitive tool to predict the neuroactivity and neurotoxicity of drugs after acute exposure. The histotypic 3D re-aggregating brain cell cultures, containing all brain cell types, were found to be well suited for OMICs analyses after both acute and long term treatment. The obtained data suggest that an in vitro ITS based on the information obtained from BBB studies and combined with metabolomics, proteomics and neuronal electrical activity measurements performed in stable in vitro neuronal cell culture systems, has high potential to improve current in vitro drug-induced neurotoxicity evaluation.

Social Presence Approach Within the Question and Answering eLearning Model: An Experiment with a Multi-Agent System

The model of Questions Answering (Q&A) for eLearning is based on collaborative learning through questions that are posed by students and their answers to that questions which are given by peers, in contrast with the classical model in which students ask questions to the teacher only. In this proposal we extend the Q&A model including the social presence concept and a quantitative measure of it is proposed; besides it is considered the evolution of the resulting Q&A social network after the inclusion of the social presence and taking into account the feedback on questions posed by students and answered by peers. The social network behaviorwas simulated using a Multi-Agent System to compare the proposed social presence model with the classical and the Q&A models

Evolutionary synthesis of stochastic gene network models using feature-based search spaces

A feature-based fitness function is applied in a genetic programming system to synthesize stochastic gene regulatory network models whose behaviour is defined by a time course of protein expression levels. Typically, when targeting time series data, the fitness function is based on a sum-of-errors involving the values of the fluctuating signal. While this approach is successful in many instances, its performance can deteriorate in the presence of noise. This thesis explores a fitness measure determined from a set of statistical features characterizing the time series' sequence of values, rather than the actual values themselves. Through a series of experiments involving symbolic regression with added noise and gene regulatory network models based on the stochastic 'if-calculus, it is shown to successfully target oscillating and non-oscillating signals. This practical and versatile fitness function offers an alternate approach, worthy of consideration for use in algorithms that evaluate noisy or stochastic behaviour.

Projection-Based Statistical Inference in Linear Structural Models with Possibly Weak Instruments

It is well known that standard asymptotic theory is not valid or is extremely unreliable in models with identification problems or weak instruments [Dufour (1997, Econometrica), Staiger and Stock (1997, Econometrica), Wang and Zivot (1998, Econometrica), Stock and Wright (2000, Econometrica), Dufour and Jasiak (2001, International Economic Review)]. One possible way out consists here in using a variant of the Anderson-Rubin (1949, Ann. Math. Stat.) procedure. The latter, however, allows one to build exact tests and confidence sets only for the full vector of the coefficients of the endogenous explanatory variables in a structural equation, which in general does not allow for individual coefficients. This problem may in principle be overcome by using projection techniques [Dufour (1997, Econometrica), Dufour and Jasiak (2001, International Economic Review)]. AR-types are emphasized because they are robust to both weak instruments and instrument exclusion. However, these techniques can be implemented only by using costly numerical techniques. In this paper, we provide a complete analytic solution to the problem of building projection-based confidence sets from Anderson-Rubin-type confidence sets. The latter involves the geometric properties of “quadrics” and can be viewed as an extension of usual confidence intervals and ellipsoids. Only least squares techniques are required for building the confidence intervals. We also study by simulation how “conservative” projection-based confidence sets are. Finally, we illustrate the methods proposed by applying them to three different examples: the relationship between trade and growth in a cross-section of countries, returns to education, and a study of production functions in the U.S. economy.

Finite-Sample Simulation-Based Inference in VAR Models with Applications to Order Selection and Causality Testing

Statistical tests in vector autoregressive (VAR) models are typically based on large-sample approximations, involving the use of asymptotic distributions or bootstrap techniques. After documenting that such methods can be very misleading even with fairly large samples, especially when the number of lags or the number of equations is not small, we propose a general simulation-based technique that allows one to control completely the level of tests in parametric VAR models. In particular, we show that maximized Monte Carlo tests [Dufour (2002)] can provide provably exact tests for such models, whether they are stationary or integrated. Applications to order selection and causality testing are considered as special cases. The technique developed is applied to quarterly and monthly VAR models of the U.S. economy, comprising income, money, interest rates and prices, over the period 1965-1996.

Region-Based Feature Interpretation for Recognizing 3D Models in 2D Images

In model-based vision, there are a huge number of possible ways to match model features to image features. In addition to model shape constraints, there are important match-independent constraints that can efficiently reduce the search without the combinatorics of matching. I demonstrate two specific modules in the context of a complete recognition system, Reggie. The first is a region-based grouping mechanism to find groups of image features that are likely to come from a single object. The second is an interpretive matching scheme to make explicit hypotheses about occlusion and instabilities in the image features.

New Architectural Models for Visibly Controllable Computing: The Relevance of Dynamic Object Oriented Architectures and Plan Based Computing Models

Traditionally, we've focussed on the question of how to make a system easy to code the first time, or perhaps on how to ease the system's continued evolution. But if we look at life cycle costs, then we must conclude that the important question is how to make a system easy to operate. To do this we need to make it easy for the operators to see what's going on and to then manipulate the system so that it does what it is supposed to. This is a radically different criterion for success. What makes a computer system visible and controllable? This is a difficult question, but it's clear that today's modern operating systems with nearly 50 million source lines of code are neither. Strikingly, the MIT Lisp Machine and its commercial successors provided almost the same functionality as today's mainstream sytsems, but with only 1 Million lines of code. This paper is a retrospective examination of the features of the Lisp Machine hardware and software system. Our key claim is that by building the Object Abstraction into the lowest tiers of the system, great synergy and clarity were obtained. It is our hope that this is a lesson that can impact tomorrow's designs. We also speculate on how the spirit of the Lisp Machine could be extended to include a comprehensive access control model and how new layers of abstraction could further enrich this model.

Transition between metadata models: approach based on the use open source software

This article shows the work developed for adapting metadata conform to the official Colombian metadata standard NTC 4611 to the international standard ISO 19115. CatMDedit, an open source metadata editor, is used in this task. CatMDedit is able of import variants of CSDGM such as NTC 4611 and export to the stable version of ISO 19139 (the XML implementation model of ISO 19115)

Application of cognitive diagnosis models to competency-based situational judgment tests

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A proposal for the diagnosis of uncertain dynamic systems based on interval models

The performance of a model-based diagnosis system could be affected by several uncertainty sources, such as,model errors,uncertainty in measurements, and disturbances. This uncertainty can be handled by mean of interval models.The aim of this thesis is to propose a methodology for fault detection, isolation and identification based on interval models. The methodology includes some algorithms to obtain in an automatic way the symbolic expression of the residual generators enhancing the structural isolability of the faults, in order to design the fault detection tests. These algorithms are based on the structural model of the system. The stages of fault detection, isolation, and identification are stated as constraint satisfaction problems in continuous domains and solved by means of interval based consistency techniques. The qualitative fault isolation is enhanced by a reasoning in which the signs of the symptoms are derived from analytical redundancy relations or bond graph models of the system. An initial and empirical analysis regarding the differences between interval-based and statistical-based techniques is presented in this thesis. The performance and efficiency of the contributions are illustrated through several application examples, covering different levels of complexity.

Collaborative recommender agents based on case-based reasoning and trust

La comunitat científica que treballa en Intel·ligència Artificial (IA) ha dut a terme una gran quantitat de treball en com la IA pot ajudar a les persones a trobar el que volen dins d'Internet. La idea dels sistemes recomanadors ha estat extensament acceptada pels usuaris. La tasca principal d'un sistema recomanador és localitzar ítems, fonts d'informació i persones relacionades amb els interessos i preferències d'una persona o d'un grup de persones. Això comporta la construcció de models d'usuari i l'habilitat d'anticipar i predir les preferències de l'usuari. Aquesta tesi està focalitzada en l'estudi de tècniques d'IA que millorin el rendiment dels sistemes recomanadors. Inicialment, s'ha dut a terme un anàlisis detallat de l'actual estat de l'art en aquest camp. Aquest treball ha estat organitzat en forma de taxonomia on els sistemes recomanadors existents a Internet es classifiquen en 8 dimensions generals. Aquesta taxonomia ens aporta una base de coneixement indispensable pel disseny de la nostra proposta. El raonament basat en casos (CBR) és un paradigma per aprendre i raonar a partir de la experiència adequat per sistemes recomanadors degut als seus fonaments en el raonament humà. Aquesta tesi planteja una nova proposta de CBR aplicat al camp de la recomanació i un mecanisme d'oblit per perfils basats en casos que controla la rellevància i edat de les experiències passades. Els resultats experimentals demostren que aquesta proposta adapta millor els perfils als usuaris i soluciona el problema de la utilitat que pateixen el sistemes basats en CBR. Els sistemes recomanadors milloren espectacularment la qualitat dels resultats quan informació sobre els altres usuaris és utilitzada quan es recomana a un usuari concret. Aquesta tesi proposa l'agentificació dels sistemes recomanadors per tal de treure profit de propietats interessants dels agents com ara la proactivitat, la encapsulació o l'habilitat social. La col·laboració entre agents es realitza a partir del mètode de filtratge basat en la opinió i del mètode col·laboratiu de filtratge a partir de confiança. Els dos mètodes es basen en un model social de confiança que fa que els agents siguin menys vulnerables als altres quan col·laboren. Els resultats experimentals demostren que els agents recomanadors col·laboratius proposats milloren el rendiment del sistema mentre que preserven la privacitat de les dades personals de l'usuari. Finalment, aquesta tesi també proposa un procediment per avaluar sistemes recomanadors que permet la discussió científica dels resultats. Aquesta proposta simula el comportament dels usuaris al llarg del temps basat en perfils d'usuari reals. Esperem que aquesta metodologia d'avaluació contribueixi al progrés d'aquesta àrea de recerca.