Learning from Ordinal Data with Inductive Logic Programming in Description Logic

Here we describe a Description Logic (DL) based Inductive Logic Programming (ILP) algorithm for learning relations of order. We test our algorithm on the task of learning user preferences from pairwise comparisons. The results have implications for the development of customised recommender systems for e-commerce, and more broadly, wherever DL-based representations of knowledge, such as OWL ontologies, are used. The use of DL makes for easy integration with such data, and produces hypotheses that are easy to interpret by novice users. The proposed algorithm outperforms SVM, Decision Trees and Aleph on data from two domains

Presence and distribution of urocortin and corticotrophin-releasing hormone receptors in the bovine thyroid gland

Urocortin (UCN), a 40 amino acid peptide is a Corticotrophin-Releasing Hormone (CRH) related peptide. The biological actions of CRH family peptides are mediated via two types of G-protein coupled receptors, CRH type 1 (CRHR1) and CRH type 2 (CRHR2). The aim of the present study was to investigate the expression of UCN, CRHR1 and CRHR2 by immunoprecipitation, Western blot, immunohistochemistry and RT-PCR in the bovine thyroid gland. Immunoprecipitation and Western blot analysis showed that tissue extracts reacted with the anti-UCN, -CRHR1 and –CRHR2 antibodies. RT-PCR experiments demonstrated that mRNAs of UCN, CRHR1 and CRHR2 were expressed. UCN-immunoreactivity (IR) and CRHR2–IR were found in the thyroid follicular and parafollicular cells and CRHR1-IR in the smooth muscle of the blood vessels. These results suggest that a regulatory system exists in the bovine thyroid gland based on UCN, CRHR1 and CRHR2 and that UCN plays a role in the regulation of thyroid physiological functions through an autocrine/paracrine mechanis

Association of nicotine metabolism and sex with relapse following varenicline and nicotine replacement therapy.

Nicotine is metabolized into cotinine and then into trans-3'-hydroxycotinine, mainly by cytochrome P450 2A6. Recent studies reported better effectiveness of varenicline in women and in nicotine normal metabolizers phenotypically determined by nicotine-metabolite ratio. Our objective was to study the influence of nicotine-metabolite ratio, CYP2A6 genotype and sex on the response to nicotine replacement therapy and varenicline. Data were extracted from a longitudinal study which included smokers participating in a smoking cessation program. Response to treatment was defined by the absence of relapse when a set threshold of reduction in cigarettes per day relative to the week before the study was no more reached. The analysis considered total and partial reduction defined by a diminution of 100% and of 90% in cigarettes per day, respectively. The hazard ratio of relapsing was estimated in multivariate Cox regression models including the sex and the nicotine metabolism determined by the phenotype or by CYP2A6 genotyping (rs1801272 and rs28399433). In the normal metabolizers determined by phenotyping and in women, the hazard ratio for relapsing was significantly lower with varenicline for a partial decrease (HR = 0.33, 95% CI [0.12, 0.89] and HR = 0.20, 95% CI [0.04, 0.91], respectively) and nonsignificantly lower for a total cessation (HR = 0.45, 95% CI [0.20, 1.0] and HR = 0.38, 95% CI [0.14, 1.0]). When compared with the normal metabolizers determined by phenotyping, the hazard ratio for a partial decrease was similar in the normal metabolizers determined by genotyping (HR = 0.42, 95% CI [0.18, 0.94]) while it was significantly lower with varenicline for a total cessation (HR = 0.50, 95% CI [0.26, 0.98]). Women and normal nicotine metabolizers may benefit more from varenicline over nicotine replacement therapy. (PsycINFO Database Recor

Learning implicational models of universal grammar parameters

The use of parameters in the description of natural language syntax has to balance between the need to discriminate among (sometimes subtly different) languages, which can be seen as a cross-linguistic version of Chomsky's descriptive adequacy (Chomsky, 1964), and the complexity of the acquisition task that a large number of parameters would imply, which is a problem for explanatory adequacy. Here we first present a novel approach in which machine learning is used to detect hidden dependencies in a table of parameters. The result is a dependency graph in which some of the parameters can be fully predicted from others. These findings can be then subjected to linguistic analysis, which may either refute them by providing typological counter-examples of languages not included in the original dataset, dismiss them on theoretical grounds, or uphold them as tentative empirical laws worth of further study. Machine learning is also used to explore the full sets of parameters that are sufficient to distinguish one historically established language family from others. These results provide a new type of empirical evidence about the historical adequacy of parameter theories

Association of Pharmacogenetic Markers with Premature Discontinuation of First-line Anti-HIV Therapy: An Observational Cohort Study

Background. Poor tolerance and adverse drug reactions are main reasons for discontinuation of antiretroviral therapy (ART). Identifying predictors of ART discontinuation is a priority in HIV care. Methods. A genetic association study in an observational cohort to evaluate the association of pharmacogenetic markers with time to treatment discontinuation during the first year of ART. Analysis included 577 treatment-naive individuals initiating tenofovir (n = 500) or abacavir (n = 77), with efavirenz (n = 272), lopinavir/ritonavir (n = 184), or atazanavir/ritonavir (n = 121). Genotyping included 23 genetic markers in 15 genes associated with toxicity or pharmacokinetics of the study medication. Rates of ART discontinuation between groups with and without genetic risk markers were assessed by survival analysis using Cox regression models. Results. During the first year of ART, 190 individuals (33%) stopped 1 or more drugs. For efavirenz and atazanavir, individuals with genetic risk markers experienced higher discontinuation rates than individuals without (71.15% vs 28.10%, and 62.5% vs 14.6%, respectively). The efavirenz discontinuation hazard ratio (HR) was 3.14 (95% confidence interval (CI): 1.35-7.33, P = .008). The atazanavir discontinuation HR was 9.13 (95% CI: 3.38-24.69, P < .0001). Conclusions. Several pharmacogenetic markers identify individuals at risk for early treatment discontinuation. These markers should be considered for validation in the clinical settin

Using ILP to Detect Anomalies in Pipelines

Simulated data generated from an accurate modelling tool can demonstrate real-life events. This approach mimics pipeline opera- tion without the need for maintaining the original anomaly record that is already scarce in the pipeline industry. This synthetic data carries precise signatures and the shape of the curve depicts the type of alarm. Learning rules can be inferred from this parametric data and the examples are con- strued from the threshold levels. The issue is addressed by considering the method that lessens data handling and the associated complexity of the problem. Probabilistic ILPs can be the most appropriate candidate for classifying anomalies of this nature. A logic program addresses this issue by learning the parameters of a program given the structure (the rules), using the ability to incorporate probability in logic programming, interpreting the examples for target predicate, and refining background knowledge for the dissemination of discoveries. This synthetic data also develops a direct link with the ILP parameter learning for competing hypotheses. The modelling tool will receive feedback, check and tune the hypothesis until exclusivity is evolved. This will fall in the domain of closed-loop active learnin

Health care provider communication training in rural Tanzania empowers HIV-infected patients on antiretroviral therapy to discuss adherence problems

Objectives: Self-reported adherence assessment in HIV-infected patients on antiretroviral therapy (ART) is challenging and may overestimate adherence. The aim of this study was to improve the ability of health care providers to elicit patients’ reports of nonadherence using a “patient-centred” approach in a rural sub-Saharan African setting. Methods: A prospective interventional cohort study of HIV-infected patients on ART for ≥ 6 months attending an HIV clinic in rural Tanzania was carried out. The intervention consisted of a 2-day workshop for health care providers on patient-centred communication and the provision of an adherence assessment checklist for use in the consultations. Patients’ self-reports of nonadherence (≥ 1 missed ART dose/4 weeks), subtherapeutic plasma ART concentrations (< 2.5th percentile of published population-based pharmacokinetic models), and virological and immunological failure according to the World Health Organization definition were assessed before and after (1–3 and 6–9 months after) the intervention. Results: Before the intervention, only 3.3% of 299 patients included in the study reported nonadherence. Subtherapeutic plasma ART drug concentrations and virological and immunological failure were recorded in 6.5%, 7.7% and 14.5% of the patients, respectively. Two months after the intervention, health care providers detected significantly more patients reporting nonadherence compared with baseline (10.7 vs. 3.3%, respectively; P < 0.001), decreasing to 5.7% after 6–9 months. A time trend towards higher drug concentrations was observed for efavirenz but not for other drugs. The virological failure rate remained unchanged whereas the immunological failure rate decreased from 14.4 to 8.7% at the last visit (P = 0.002). Conclusions: Patient-centred communication can successfully be implemented with a simple intervention in rural Africa. It increases the likelihood of HIV-infected patients reporting problems with adherence to ART; however, sustainability remains a challenge

Estudio de la contribución de los factores genéticos a la variabilidad farmacocinética y farmacodinámica de los inhibidores de la HMG-CoA reductasa en voluntarios sanos

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina. Departamento de Farmacología y Terapéutica. Fecha de lectura: 20 de Abril de 201