Automatic filtering and substantiation of drug safety signals

Drug safety issues pose serious health threats to the population and constitute a major cause of mortality worldwide. Due to the prominent implications to both public health and the pharmaceutical industry, it is of great importance to unravel the molecular mechanisms by which an adverse drug reaction can be potentially elicited. These mechanisms can be investigated by placing the pharmaco-epidemiologically detected adverse drug reaction in an information-rich context and by exploiting all currently available biomedical knowledge to substantiate it. We present a computational framework for the biological annotation of potential adverse drug reactions. First, the proposed framework investigates previous evidences on the drug-event association in the context of biomedical literature (signal filtering). Then, it seeks to provide a biological explanation (signal substantiation) by exploring mechanistic connections that might explain why a drug produces a specific adverse reaction. The mechanistic connections include the activity of the drug, related compounds and drug metabolites on protein targets, the association of protein targets to clinical events, and the annotation of proteins (both protein targets and proteins associated with clinical events) to biological pathways. Hence, the workflows for signal filtering and substantiation integrate modules for literature and database mining, in silico drug-target profiling, and analyses based on gene-disease networks and biological pathways. Application examples of these workflows carried out on selected cases of drug safety signals are discussed. The methodology and workflows presented offer a novel approach to explore the molecular mechanisms underlying adverse drug reactions

Posibles causas de la reducci��n de la poblaci��n penitenciaria en Espa��a y Catalu��a entre 2010 y 2013 : Efecto de la Ley Org��nica 5/2010 sobre esta reducci��n

Desde 1980 hasta 2010, la poblaci��n penitenciaria no dej�� de crecer. Sin embargo, desde 2010 esta tasa se est�� reduciendo. En este trabajo se trata de buscar una serie de explicaciones para este aumento, y para la posterior reducci��n. Se pone especialatenci��n en la entrada en vigor de la Ley Org��nica 5/2010, que supuso una extensa reforma del C��digo Penal. Con esta Ley Org��nica, se introdujo la posibilidad de reducir en un grado ciertas conductas contra la salud p��blica, en forma de subtipo atenuado.Esto puede haber supuesto un efecto considerable sobre la reducci��n de las tasas de encarcelamiento. Para estudiar el efecto de este nuevo subtipo, se realiza una peque��a investigaci��n cuantitativa sobre una muestra de sentencias por delitos contra la saludp��blica. Despu��s, se muestran los resultados y se proponen nuevas l��neas de investigaci��n.

The EU-ADR Web Platform: delivering advanced pharmacovigilance tools

PURPOSE: Pharmacovigilance methods have advanced greatly during the last decades, making post-market drug assessment an essential drug evaluation component. These methods mainly rely on the use of spontaneous reporting systems and health information databases to collect expertise from huge amounts of real-world reports. The EU-ADR Web Platform was built to further facilitate accessing, monitoring and exploring these data, enabling an in-depth analysis of adverse drug reactions risks.METHODS: The EU-ADR Web Platform exploits the wealth of data collected within a large-scale European initiative, the EU-ADR project. Millions of electronic health records, provided by national health agencies, are mined for specific drug events, which are correlated with literature, protein and pathway data, resulting in a rich drug-event dataset. Next, advanced distributed computing methods are tailored to coordinate the execution of data-mining and statistical analysis tasks. This permits obtaining a ranked drug-event list, removing spurious entries and highlighting relationships with high risk potential.RESULTS: The EU-ADR Web Platform is an open workspace for the integrated analysis of pharmacovigilance datasets. Using this software, researchers can access a variety of tools provided by distinct partners in a single centralized environment. Besides performing standalone drug-event assessments, they can also control the pipeline for an improved batch analysis of custom datasets. Drug-event pairs can be substantiated and statistically analysed within the platform's innovative working environment.CONCLUSIONS: A pioneering workspace that helps in explaining the biological path of adverse drug reactions was developed within the EU-ADR project consortium. This tool, targeted at the pharmacovigilance community, is available online at https://bioinformatics.ua.pt/euadr/. Copyright �� 2012 John Wiley & Sons, Ltd.

Elaboraci�� d"una base de dades per a l"autoformaci�� i autoavaluaci�� de coneixements i compet��ncies en estudis cient��fics superiors

L'objectiu principal ��s oferir uns recursos educatius multim��dia (en format HTML i JAVA) utilitzables en l��nea (Internet) o en suport aut��nom (CD-ROM) per a l'autoformaci�� i l'autoevaluaci�� ...

Determination of the components of the gyration tensor of quartz by oblique incidence transmission two-modulator generalized ellipsometry

The two independent components of the gyration tensor of quartz, g11 and g33, have been spectroscopically measured using a transmission two-modulator generalized ellipsometer. The method is used to determine the optical activity in crystals in directions other than the optic axis, where the linear birefringence is much larger than the optical activity.

Zim17/Tim15 links mitochondrial iron���sulfur cluster biosynthesis to nuclear genome stability

Genomic instability is related to a wide-range of human diseases. Here, we show that mitochondrial iron���sulfur cluster biosynthesis is important for the maintenance of nuclear genome stability in Saccharomyces cerevisiae. Cells lacking the mitochondrial chaperone Zim17 (Tim15/Hep1), a component of the iron���sulfur biosynthesis machinery, have limited respiration activity, mimic the metabolic response to iron starvation and suffer a dramatic increase in nuclear genome recombination. Increased oxidative damage or deficient DNA repair do not account for the observed genomic hyperrecombination. Impaired cell-cycle progression and genetic interactions of ZIM17 with components of the RFC-like complex involved in mitotic checkpoints indicate that replicative stress causes hyperrecombination in zim17�� mutants. Furthermore, nuclear accumulation of pre-ribosomal particles in zim17�� mutants reinforces the importance of iron���sulfur clusters in normal ribosome biosynthesis. We propose that compromised ribosome biosynthesis and cell-cycle progression are interconnected, together contributing to replicative stress and nuclear genome instability in zim17�� mutants.

In situ spectroellipsometric study of the nucleation and growth of amorphous silicon

A detailed in situ spectroellipsometric analysis of the nucleation and growth of hydrogenated amorphous silicon (a:Si:H) is presented. Photoelectronic quality a���Si:H films are deposited by plasma���enhanced chemical vapor deposition on smooth metal (NiCr alloy) and crystalline silicon (c���Si) substrates. The deposition of a���Si:H is analyzed from the first monolayer up to a final thickness of 1.2 ��m. In order to perform an improved analysis, real time ellipsometric trajectories are recorded, using fixed preparation conditions, at various photon energies ranging from 2.2 to 3.6 eV. The advantage of using such a spectroscopic experimental procedure is underlined. New insights into the nucleation and growth mechanisms of a���Si:H are obtained. The nucleation mechanism on metal and c���Si substrates is very accurately described assuming a columnar microstructural development during the early stage of the growth. Then, as a consequence of the incomplete coalescence of the initial nuclei, a surface roughness at the 10-15 �� scale is identified during the further growth of a���Si:H on both substrates. The bulk a���Si:H grows homogeneously beneath the surface roughness. Finally, an increase of the surface roughness is evidenced during the long term growth of a���Si:H. However, the nature of the substrate influenced the film growth. In particular, the film thickness involved in the nucleation���coalescence phase is found lower in the case of c���Si (67��8 ��) as compared to NiCr (118��22 ��). Likewise films deposited on c���Si present a smaller surface roughness even if thick samples are considered (>1 ��m). More generally, the present study illustrates the capability of in situ spectroellipsometry to precisely analyze fundamental processes in thin���film growth, but also to monitor the preparation of complex structures on a few monolayers scale.

Properties of amorphous silicon thin films grown in square wave modulated silane rf discharges.

Hydrogenated amorphous silicon (a���Si:H) thin films have been obtained from pure SiH4 rf discharges by using the square wave modulation (SQWM) method. Film properties have been studied by means of spectroellipsometry, thermal desorption spectrometry, photothermal deflection spectroscopy and electrical conductivity measurements, as a function of the modulation frequency of the rf power amplitude (0.2-4000 Hz). The films deposited at frequencies about 1 kHz show the best structural and optoelectronic characteristics. Based upon the experimental results, a qualitative model is presented, which points up the importance of plasma negative ions in the deposition of a���Si:H from SQWM rf discharges through their influence on powder particle formation.

Determinaci��n de la paleosalinidad, mediante la relaci��n Br/Cl, en las sales de la cuenca pot��sica catalana (Sallent, Barcelona, Espa��a)

Debido a su acumdaci��n en las salmueras de las cubetas de deposici��n evapor��tica, el Br se concentra progresivamente en los ultimos precipitados de los cloruros. La relaci��n Br/Cl ha sido utilizada (BOEKE y EITEL, 1923; D'ANS y K��HN, 1944) para determinar variaciones en la concentraci��n de la salmuera durante la deposici��n evapor��tica. Para la determinaci��n cuantitativa del Br y CL en varias muestras recogidas en la explotaci��n de Sallent, se ha utilizado la fluorescencia de rayos X.

Seis aspectos de la participacion en procesos de transformacion urbana

La participaci��n ciudadana en procesos de transformaci��n del espacio p��blico se incluye cada vez con m��s fuerza en la gesti��n de las ciudades, como forma de construcci��n de urbes y ciudadan��a con consecuencias positivas en varios niveles. Pero la complejidad de este tipo de experiencias -donde ciudadan��a, Administraci��n y profesionales implicados deben trabajar a favor de una mejora substancial- retrasa y a veces paraliza este tipo de procesos, que requieren un cambio de cultura profesional y c��vica. En este art��culo no se plantean modelos ni f��rmulas, sino que se reflexiona sobre seis aspectos transversales a este tipo de experiencias participativas: la ciudadan��a como protagonista; la participaci��n como oportunidad de adaptaci��n de la urbe al ciudadano; la emergencia de la creatividad en los procesos; la relaci��n entre participaci��n y representaci��n-generaci��n de identidad; el concepto de apropiaci��n del espacio p��blico, y finalmente la necesidad de permeabilidad por parte de los agentes implicados.

La tendencia mineral��gica de las eolianitas del Pleistoceno de Mallorca, mediante la aplicaci��n del metodo de Chung

El objetivo de este trabajo es conocer la evoluci��n diagen��tica de los minerales carbonatados de las eolianitas del Pleistoceno de Mallorca. Se ha puesto de relieve un control de la composici��n original y un control clim��tico en la tendencia mineral��gica de las eolianitas. Para la determinaci��n cuantitativa se ha utilizado el m��todo de Chung.

Mueller matrix microscope with a dual continuous rotating compensator setup and digital demodulation

In this paper we describe a new Mueller matrix (MM) microscope that generalizes and makes quantitative the polarized light microscopy technique. In this instrument all the elements of the MU are simultaneously determined from the analysis in the frequency domain of the time-dependent intensity of the light beam at every pixel of the camera. The variations in intensity are created by the two compensators continuously rotating at different angular frequencies. A typical measurement is completed in a little over one minute and it can be applied to any visible wavelength. Some examples are presented to demonstrate the capabilities of the instrument.

Climate change impacts on lakes: an integrated ecological perspective based on a multi-faceted approach, with special focus on shallow lakes

Freshwater ecosystems and their biodiversity are presently seriously threatened by global development and population growth, leading to increases in nutrient inputs and intensification of eutrophication-induced problems in receiving fresh waters, particularly in lakes. Climate change constitutes another threat exacerbating the symptoms of eutrophication and species migration and loss. Unequivocal evidence of climate change impacts is still highly fragmented despite the intensive research, in part due to the variety and uncertainty of climate models and underlying emission scenarios but also due to the different approaches applied to study its effects. We first describe the strengths and weaknesses of the multi-faceted approaches that are presently available for elucidating the effects of climate change in lakes, including space-for-time substitution, time series, experiments, palaeoecology and modelling. Reviewing combined results from studies based on the various approaches, we describe the likely effects of climate changes on biological communities, trophic dynamics and the ecological state of lakes. We further discuss potential mitigation and adaptation measures to counteract the effects of climate change on lakes and, finally, we highlight some of the future challenges that we face to improve our capacity for successful prediction.

Incumbent audit firm-provided tax services and the clients with low financial reporting quality

This study investigates whether incumbent audit firm-provided tax services enhance or impair the likelihood of acknowledging client companies��� low financial reporting quality. In particular, we examine the association between tax-related fees and the likelihood of timely restatements, and internal control weakness disclosures among a sample of US companies that all have misstatements in financial information. The empirical findings indicate that companies paying higher tax-related fees are less likely to disclose SOX 404 internal control weakness disclosures, implying that underlying control problems are unacknowledged when incumbent audit firm provided tax-related fees are higher. However, the findings suggest that just providing both audit and tax-related services does not have an impact on audit quality per se, but rather it is the magnitude of the tax-related fees in particular that counts. We also find some evidence suggesting that companies paying higher tax-related fees have higher likelihood of restatement lags, whereas companies paying smaller tax-related fees to their audit firm restate financial statements in a timelier manner. Overall, the findings suggest that audit scrutiny of client companies with low quality financial reporting is weaker when the magnitude of tax-related fees is higher.

Brideshead Revisited (1945) by Evelyn Waugh (1903-1966): the benefit of an Arcadian experience in confronting the human tragedy

As the frontispiece of Book One of Evelyn Waugh���s Brideshead Revisited, the phrase ���Et in Arcadia ego��� announces the author���s intention of making the classical Arcadian theme a key reference in a text that speaks of nostalgia for a joyful past in times marked by sadness and pain. However, an interpretation may be approached from several directions even within the classical tradition. Thus, without ignoring philological or artistic aspects of the topic, this article focuses on a close study of the author���s most original message: the notion that a youthful Arcadian experience confers on young men and women a ���residue of happiness��� able to sustain their future development and assist them in dealing with the challenges of personal tragedy.