CNS safety at 48-week of switching to ATV/r plus 3TC or two nucleos(t)ides in HIV-suppressed patients on stable ART: the SALT neurocognitive sub-study.

INTRODUCTION Due to their low CNS penetrance, there are concerns about the capacity of non-conventional PI-based ART (monotherapy and dual therapies) to preserve neurocognitive performance (NP). METHODS We evaluated the NP change of aviremic participants of the SALT clinical trial (1) switching therapy to dual therapy (DT: ATV/r+3TC) or triple therapy (TT: ATV/r+2NRTI) who agreed to perform an NP assessment (NPZ-5) at baseline and W48. Neurocognitive impairment and NP were assessed using AAN-2007 criteria (2) and global deficit scores (GDS) (3). Neurocognitive change (GDS change: W48 - baseline) and the effect of DT on NP evolution crude and adjusted by significant confounders were determined using ANCOVA. RESULTS A total of 158 patients were included (Table 1). They had shorter times because HIV diagnosis, ART initiation and HIV-suppression and their virologic outcome at W48 by snapshot was higher (79.1% vs 72.7%; p=0.04) compared to the 128 patients not included in the sub-study. By AAN-2007 criteria, 51 patients in each ART group (68% vs 63%) were neurocognitively impaired at baseline (p=0.61). Forty-seven patients were not reassessed at W48: 30 lost of follow-up (16 DT-14 TT) and 17 had non-evaluable data (6 DT-11 TT). Patients retested were more likely to be men (78.9% vs 61.4%) and had neurological cofounders (9.6% vs 0%) than patients non-retested. At W48, 3 out of 16 (5.7%) patients on DT and 6 out of 21 (10.5%) on TT who were non-impaired at baseline became impaired (p=0.49) while 10 out of 37 (18.9%) on DT and 7 out of 36 (12.3%) on TT who were neurocognitively impaired at baseline became non-impaired (p=0.44). Mean GDS changes (95% CI) were: Overall -0.2 (-0.3 to -0.04): DT -0.26 (-0.4 to -0.07) and TT -0.08 (-0.2 to 0.07). NP was similar between DT and TT (0.15). This absence of differences was also observed in all cognitive tests. Effect of DT: -0.16 [-0.38 to 0.06]) (r(2)=0.16) on NP evolution was similar to TT (reference), even after adjusting (DT: -0.11 [-0.33 to 0.1], TT: reference) by significant confounders (geographical origin, previous ATV use and CD4 cell count) (r(2)=0.25). CONCLUSIONS NP stability was observed after 48 weeks of follow up in the majority of patients whether DT or TT was used to maintain HIV-suppression. Incidence rates of NP impairment or NP impairment recovery were also similar between DT and TT.

The lincRNA HOTAIRM1, located in the HOXA genomic region, is expressed in acute myeloid leukemia, impacts prognosis in patients in the intermediate-risk cytogenetic category, and is associated with a distinctive microRNA signature.

Long non-coding RNAs (lncRNAs) are deregulated in several tumors, although their role in acute myeloid leukemia (AML) is mostly unknown.We have examined the expression of the lncRNA HOX antisense intergenic RNA myeloid 1 (HOTAIRM1) in 241 AML patients. We have correlated HOTAIRM1 expression with a miRNA expression profile. We have also analyzed the prognostic value of HOTAIRM1 expression in 215 intermediate-risk AML (IR-AML) patients.The lowest expression level was observed in acute promyelocytic leukemia (P < 0.001) and the highest in t(6;9) AML (P = 0.005). In 215 IR-AML patients, high HOTAIRM1 expression was independently associated with shorter overall survival (OR:2.04;P = 0.001), shorter leukemia-free survival (OR:2.56; P < 0.001) and a higher cumulative incidence of relapse (OR:1.67; P = 0.046). Moreover, HOTAIRM1 maintained its independent prognostic value within the favorable molecular subgroup (OR: 3.43; P = 0.009). Interestingly, HOTAIRM1 was overexpressed in NPM1-mutated AML (P < 0.001) and within this group retained its prognostic value (OR: 2.21; P = 0.01). Moreover, HOTAIRM1 expression was associated with a specific 33-microRNA signature that included miR-196b (P < 0.001). miR-196b is located in the HOX genomic region and has previously been reported to have an independent prognostic value in AML. miR-196b and HOTAIRM1 in combination as a prognostic factor can classify patients as high-, intermediate-, or low-risk (5-year OS: 24% vs 42% vs 70%; P = 0.004).Determination of HOTAIRM1 level at diagnosis provided relevant prognostic information in IR-AML and allowed refinement of risk stratification based on common molecular markers. The prognostic information provided by HOTAIRM1 was strengthened when combined with miR-196b expression. Furthermore, HOTAIRM1 correlated with a 33-miRNA signature.

Role of Age and Sex in the Diagnosis of Early-stage Malignant Melanoma: A Cross-Sectional study.

Age and sex have been identified as predictors of outcome in malignant melanoma (MM). This aim of this multicentre, cross-sectional study was to analyse the role of age and sex as explanatory variables for the diagnosis of thin MM. A total of 2430 patients with MM were recruited. Cases of in situ-T1 MM were more frequent than T2-T4 MM (56.26% vs. 43.74%). Breslow thickness increased throughout decades of life (analysis of variance (ANOVA) p < 0.001), with a weak correlation between Breslow thickness and patient's age (r   = 0.202, p < 0.001). Breslow thickness was significantly less in women (1.79 vs. 2.38 mm, p = 0.0001). Binary logistic regression showed a significant (p < 0.001) odds ratio for age 0-29 years (1.18), and 30-59 years (1.16), and for women (1.09). Age and sex explained 3.64% of the variation observed in Tis-T1 frequency (R2 = 0.0364). Age and sex appear to explain a low percentage of the variation in the early detection of MM.

Estudio de la tecnología VoIP a través de Elastix

Estudio sobre cómo encaja la tecnología IP en el mundo de la telefonía para ver qué ventajas e inconvenientes supone cada posible solución a un problema, y elegir la mejor.

Treball Final de Master - Servidor de Comunicacions Unificades

L'objectiu d'aquest projecte és la creació d'una prova de concepte de comunicacions unificades utilitzant productes de programari lliure existents. Aquesta prova de concepte servirà per poder fer demostracions del funcionament general del programari implicat amb el mínim de preparacions, instal·lacions i configuracions prèvies possibles. El projecte es dividirà en dos appliances o LiveCD, creats a traves de Suse Studio, anomenats Comunicacions Unificades i Comunicacions Unificades 2.Els productes de programari lliure que composen el Servidor de Comunicacions Unificades els podem classificar en productes principals, plugins o addons dels productes i productes secundaris.Com a productes principals tenim els següents servidors que cobreixen les necessitats principals del Servidor de Comunicacions Unificades:Asterisk v1.8.3 : Servidor de telefonia amb veu sobre IP (VoIP).FreePBX v2.9.0beta2 : GUI de control i administració d'Asterisk.Openfire v3.7.0 : Servidor de IM basat en el protocol XMPP.BigBlueButton v0.71a : Sistema de conferència web. Pendent finalitzar-ne l'implementació.I els seguents productes principals que cobreixen les necessitats del servidor de Comunicacions Unificades 2:Zimbra v7.0.1 : Servidor de correu electrònic i de calendari. Pendent resoldre conflicte inicialització LDAP.Funambol v9.0.0 : Sincronització Zimbra amb mòbils.Com a plugins o addons del productes tenim, classificats segons el producte:Asterisk addons: chan_jingle i chan_gtalkZimlets: Asterisk, Google Translator, Funambol i SocialsOpenfire pugins: Asterisk, Facebook i GmailCom a productes secundaris tenim els clients necessaris per poder utilitzar l'appliance:Firefox: Navegador web que servirà com a interfície d'usuari per les diferents eines d'administració i la demostració.Pigdin o Spark: Clients de missatgeria instantània, per l'appliance Comunicacions Unificades.A més d'instal·lar aquests productes, s'implementa una interfície web, mitjançant Drupal, en format HTML per enllaçar les diferents eines d'administració dels productes, per a cadascun dels dos appliances i es realitzara un Kiosk appliance per a familiaritzar-se amb l'entorn SuseStudio.

Centraleta PBX

Creació d'un producte de centraleta telefònica IP amb la integració de tots els serveis auxiliars. Això inclou la part de seguretat i els serveis de xarxa.

Estudi / implementació de la Qualitat de Servei en els entorns de xarxa i CPU

En aquest treball final de carrera es realitza estudi, així com la implementació, de la QoS (Quality of Service) en els entorns de xarxa i CPU sota el sistema operatiu Linux. L'objectiu és garantir uns determinats amples de banda, així com reservar porcions de CPU a través del nucli del S.O., per determinades aplicacions. D'aquesta manera es podrà obtenir una execució més eficient d'aquestes aplicacions.

Utilidad de la densitometría de doble energía (DEXA) en la valoración de las alteraciones morfológicas y estructurales en el paciente VIH en relación con distintos regímenes de tratamiento antiretroviral (TAR)

Objetivo: Comparar la distribución de la grasa corporal mediante DEXA, en pacientes VIH+ monoinfectados y coinfectados VHC, que reciben tratamiento antirretroviral basado en inhibidores de proteasa o no nucléosidos. Materiales y Métodos: Estudio retrospectivo, observacional, unicéntrico. Resultados: 80 pacientes, 60 hombres, 20 mujeres. 41 monoinfectados, 39 coinfectados. Edad 48 años, peso 71 kg, IMC 24, 39 IP, 41 NN. Los coinfectados tenían triglicéridos, colesterol y LDL-c inferiores a los monoinfectados (p <0.05). La DEXA no mostró diferencias en la comparación de mono/coinfectados y grupos de tratamiento. Conclusiones: No se encontraron diferencias entre grupos. Los coinfectados muestran lípidos plasmáticos inferiores.

Compendium of projects in the European nanosafety cluster

The demand for research in the area of safety health and environmental management of nanotechnologies is present since a decade and identified by several landmark reports and studies. It is not the intention of this compendium to report on these as they are widely available. It is also not the intention to publish scientific papers and research results as this task is covered by scientific conferences and the peer reviewed press. The intention of the compendium is to bring together researchers, create synergy in their work, and establish links and communication between them mainly during the actual research phase before publication of results. Towards this purpose we find useful to give emphasis to communication of projects strategic aims, extensive coverage of specific work objectives and of methods used in research, strengthening human capacities and laboratories infrastructure, supporting collaboration for common goals and joint elaboration of future plans, without compromising scientific publication potential or IP Rights. These targets are far from being achieved with the publication in its present shape. We shall continue working, though, and hope with the assistance of the research community to make significant progress. We would like to stress that this sector is under development and progressing very fast, which might make some of the statements outdated or even obsolete. Nevertheless it is intended to provide a basis for the necessary future developments. [Ed.]

Guidelines for the use and interpretation of assays for monitoring autophagy.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

Aplicación para analizar el rendimiento de red

En el presente Trabajo de Fin de Carrera se desarrolla una aplicación para analizar el rendimiento de una red Ethernet. El rendimiento se evalúa identificando los equipos que generan el tráfico presente en la red y clasificando este según los protocolos de nivel de enlace, red, transporte o aplicación al que corresponde. Esta aplicación puede ser utilizada tanto para conocer el tráfico del ordenador en el cual se ejecuta, o bien, para evaluar el tráfico en un punto concreto de la red.

Eina d'anàlisi de rendiment d'una xarxa : TaFanet v1.0

Treball de final de carrera que descriu el procés d'implementació de TaFanet v1.0.

Role of the cannabinoid system in the effects induced by nicotine on anxiety-like behaviour in mice

Rationale: Acute behavioural effects and motivational responses induced by nicotine can be modulated by the endocannabinoid system supporting the existence of a physiological interaction between these two systems. Objectives: The present study was designed to examine the possible involvement of the cannabinoid system in the anxiolytic- and anxiogenic-like responses induced by nicotine in mice. Methods: Animals were only exposed once to nicotine. The acute administration of low (0.05, sc) or high (0.8 mg/kg, sc) doses of nicotine produced opposite effects in the elevated plus-maze, i.e., anxiolytic- and anxiogenic-like responses, respectively. The effects of the pretreatment with the CB1 cannabinoid receptor antagonist, rimonabant (0.25, 0.5 and 1 mg/kg, ip), and the cannabinoid agonist, 9-tetrahydrocannabinol (0.1 mg/kg, ip), were evaluated on the anxiolytic- and anxiogenic-like responses induced by nicotine. Results: Rimonabant completely abolished nicotine-induced anxiolytic-like effects and increased the anxiogenic-like responses of nicotine, suggesting an involvement of CB1 receptors in these behavioural responses. On the other hand, 9-tetrahydrocannabinol failed to modify nicotine anxiolytic-like responses, but attenuated its anxiogenic-like effects. In addition the association of non-effective doses of 9-tetrahydrocannabinol and nicotine produced clear anxiolytic-like responses. Conclusions: These results demonstrate that the endogenous cannabinoid system is involved in the regulation of nicotine anxiety-like behaviour in mice, and provide new findings to support the use of cannabinoid antagonists in the treatment of tobacco addiction.

Cross recurrence quantification for cover song identification

There is growing evidence that nonlinear time series analysis techniques can be used to successfully characterize, classify, or process signals derived from realworld dynamics even though these are not necessarily deterministic and stationary. In the present study we proceed in this direction by addressing an important problem our modern society is facing, the automatic classification of digital information. In particular, we address the automatic identification of cover songs, i.e. alternative renditions of a previously recorded musical piece. For this purpose we here propose a recurrence quantification analysis measure that allows tracking potentially curved and disrupted traces in cross recurrence plots. We apply this measure to cross recurrence plots constructed from the state space representation of musical descriptor time series extracted from the raw audio signal. We show that our method identifies cover songs with a higher accuracy as compared to previously published techniques. Beyond the particular application proposed here, we discuss how our approach can be useful for the characterization of a variety of signals from different scientific disciplines. We study coupled Rössler dynamics with stochastically modulated mean frequencies as one concrete example to illustrate this point.

IL28B expression depends on a novel TT/-G polymorphism which improves HCV clearance prediction.

Approximately 3% of the world population is chronically infected with the hepatitis C virus (HCV), with potential development of cirrhosis and hepatocellular carcinoma. Despite the availability of new antiviral agents, treatment remains suboptimal. Genome-wide association studies (GWAS) identified rs12979860, a polymorphism nearby IL28B, as an important predictor of HCV clearance. We report the identification of a novel TT/-G polymorphism in the CpG region upstream of IL28B, which is a better predictor of HCV clearance than rs12979860. By using peripheral blood mononuclear cells (PBMCs) from individuals carrying different allelic combinations of the TT/-G and rs12979860 polymorphisms, we show that induction of IL28B and IFN-γ-inducible protein 10 (IP-10) mRNA relies on TT/-G, but not rs12979860, making TT/-G the only functional variant identified so far. This novel step in understanding the genetic regulation of IL28B may have important implications for clinical practice, as the use of TT/G genotyping instead of rs12979860 would improve patient management.