Las personas mayores ante la crisis económica

La comunicació consisteix en una anàlisi dels efectes de la crisi sobre les persones grans a partir de l’exploració de dades estadístiques i d’un ampli treball de camp qualitatiu fet amb persones grans durant l’any 2013. S’elabora al seu torn una tipologia temptativa d’impactes de la crisi en aquest grup, discutint com s’insereixen aquests canvis en les trajectòries de vida i les xarxes socials de la gent gran, quins són els elements que generen una major vulnerabilitat i, finalment, en quina mesura les alteracions econòmiques produïdes per la crisi es tradueixen també en transformacions en el seu rol econòmic, social i familiar.

Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria: a literature review and meta-analysis of individual patient data.

BACKGROUND: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). METHODS: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. RESULTS: In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P <0.001); fever (>37.5 °C) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). CONCLUSIONS: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility.

Structural Insight into the Mode of Action of a Direct Inhibitor of Coregulator Binding to the Thyroid Hormone Receptor.

The development of nuclear hormone receptor antagonists that directly inhibit the association of the receptor with its essential coactivators would allow useful manipulation of nuclear hormone receptor signaling. We previously identified 3-(dibutylamino)-1-(4-hexylphenyl)-propan-1-one (DHPPA), an aromatic β-amino ketone that inhibits coactivator recruitment to thyroid hormone receptor β (TRβ), in a high-throughput screen. Initial evidence suggested that the aromatic β-enone 1-(4-hexylphenyl)-prop-2-en-1-one (HPPE), which alkylates a specific cysteine residue on the TRβ surface, is liberated from DHPPA. Nevertheless, aspects of the mechanism and specificity of action of DHPPA remained unclear. Here, we report an x-ray structure of TRβ with the inhibitor HPPE at 2.3-Å resolution. Unreacted HPPE is located at the interface that normally mediates binding between TRβ and its coactivator. Several lines of evidence, including experiments with TRβ mutants and mass spectroscopic analysis, showed that HPPE specifically alkylates cysteine residue 298 of TRβ, which is located near the activation function-2 pocket. We propose that this covalent adduct formation proceeds through a two-step mechanism: 1) β-elimination to form HPPE; and 2) a covalent bond slowly forms between HPPE and TRβ. DHPPA represents a novel class of potent TRβ antagonist, and its crystal structure suggests new ways to design antagonists that target the assembly of nuclear hormone receptor gene-regulatory complexes and block transcription.

Evaluación de las curvaturas locales de un frente de onda mediante interferometria de difracción por múltiples puntos

El objetivo fundamental de este trabajo es modificar el diseño clásico del interferómetro de difracción por punto para que permita medir simultáneamente las curvaturas locales de la fase de una onda en distintos puntos de un plano transversal a la dirección de propagación de un haz de luz con aberraciones. Para ello, y como segundo objetivo, propondremos un método de cálculo nuevo y sencillo que nos permitirá diseñar el componente fundamental del interferómetro para cada aplicación deseada.

Anàlisis antropològica de les restes neolítiques de la Caserna de Sant Pau (Biometria, Dentició, ADN i Microestriació Dentària).

Les restes esquelètiques analitzades corresponen tant al nivell neolític (n=26) com a l"època del bronze (n=2), encara que aquí es presenten tan sols els resultats de la població neolítica (taula 1). En tots els casos les sepultures són individuals, amb l"única excepció de la sepultura 20, on s"han recuperat les restes corresponents a un individu femení adult (CSP201) i un fetus (CSP202) (taula 1). Per tal de caracteritzar biomètricament la població s"ha emprat la metodologia proposada per Martin i Saller (1959), Brothwell (1981) i Bass (1971). La determinació del sexe s"ha realitzat a través dels caràcters sexuals secundaris del crani i de la pelvis, i se"n pot trobar una descripció més detallada a Estebaranz et alii (2007). En el cas específic de les paleopatologies es van seguir les recomanacions de Campillo (Campillo, 1977).

Allosteric conversation in the androgen receptor ligand-binding domain surfaces

Androgen receptor (AR) is a major therapeutic target that plays pivotal roles in prostate cancer (PCa) and androgen insensitivity syndromes. We previously proposed that compounds recruited to ligand-binding domain (LBD) surfaces could regulate AR activity in hormone-refractory PCa and discovered several surface modulators of AR function. Surprisingly, the most effective compounds bound preferentially to a surface of unknown function [binding function 3 (BF-3)] instead of the coactivator-binding site [activation function 2 (AF-2)]. Different BF-3 mutations have been identified in PCa or androgen insensitivity syndrome patients, and they can strongly affect AR activity. Further, comparison of AR x-ray structures with and without bound ligands at BF-3 and AF-2 showed structural coupling between both pockets. Here, we combine experimental evidence and molecular dynamic simulations to investigate whether BF-3 mutations affect AR LBD function and dynamics possibly via allosteric conversation between surface sites. Our data indicate that AF-2 conformation is indeed closely coupled to BF-3 and provide mechanistic proof of their structural interconnection. BF-3 mutations may function as allosteric elicitors, probably shifting the AR LBD conformational ensemble toward conformations that alter AF-2 propensity to reorganize into subpockets that accommodate N-terminal domain and coactivator peptides. The induced conformation may result in either increased or decreased AR activity. Activating BF-3 mutations also favor the formation of another pocket (BF-4) in the vicinity of AF-2 and BF-3, which we also previously identified as a hot spot for a small compound. We discuss the possibility that BF-3 may be a protein-docking site that binds to the N-terminal domain and corepressors. AR surface sites are attractive pharmacological targets to develop allosteric modulators that might be alternative lead compounds for drug design.

Ironías de la ironía: argumento dialéctico, figura retórica o categoría estética

[spa] El artículo plantea una breve revisión de la idea de ironía desde el punto de vista de la retórica y sus derivaciones en algunos de los estudios lingüísticos del siglo XX. Se parte de la clasificación tradicional de la ironía socrática, la ironía retórica y la ironía romántica para centrar el análisis en aspectos básicos del fenómeno irónico tales como la oposición, la verosimilitud, la complicidad con el intérprete o el papel desempeñado por el contexto. [eng] This article is a brief review of the concept of irony from the point of view of rhetoric and its influences in some of the twentieth century linguistic studies. The review begins with the traditional classification of Socratic irony, rhetoric irony and romantic irony in order to focus the analysis on some fundamental elements of ironic phenomenon such as opposition, verisimilitude, camaraderie with the interpreter or the role played by the context.

Pego do Diabo (Loures, Portugal): Dating the Emergence of Anatomical Modernity in Westernmost Eurasia

Neandertals and the Middle Paleolithic persisted in the Iberian Peninsula south of the Ebro drainage system for several millennia beyond their assimilation/replacement elsewhere in Europe. As only modern humans are associated with the later stages of the Aurignacian, the duration of this persistence pattern can be assessed via the dating of diagnostic occurrences of such stages.

Análisis estadístico de la litigiosidad en los Tribunales Económico-Administrativos Regionales y Central

El presente artículo versa sobre la litigiosidad acaecida en los Tribunales Económico Administrativos Regionales y Locales, así como en el Tribunal Económico Administrativo Central, a cuyo fin se lleva a cabo una visión comparada de la conflictividad tributaria observada en las diferentes Comunidades Autónomas, con especial incidencia en los T.E.A.R.s de las Comunidades de Andalucía, Madrid, Cataluña y Valencia. Dedicamos la segunda parte del estudio a la litigiosidad registrada en el Tribunal Económico-Administrativo Central.