MGMT methylation status: the advent of stratified therapy in glioblastoma?

Glioblastomas are the most malignant gliomas with median survival times of only 15 months despite modern therapies. All standard treatments are palliative. Pathogenetic factors are diverse, hence, stratified treatment plans are warranted considering the molecular heterogeneity among these tumors. However, most patients are treated with "one fits all" standard therapies, many of them with minor response and major toxicities. The integration of clinical and molecular information, now becoming available using new tools such as gene arrays, proteomics, and molecular imaging, will take us to an era where more targeted and effective treatments may be implemented. A first step towards the design of such therapies is the identification of relevant molecular mechanisms driving the aggressive biological behavior of glioblastoma. The accumulation of diverse aberrations in regulatory processes enables tumor cells to bypass the effects of most classical therapies available. Molecular alterations underlying such mechanisms comprise aberrations on the genetic level, such as point mutations of distinct genes, or amplifications and deletions, while others result from epigenetic modifications such as aberrant methylation of CpG islands in the regulatory sequence of genes. Epigenetic silencing of the MGMT gene encoding a DNA repair enzyme was recently found to be of predictive value in a randomized clinical trial for newly diagnosed glioblastoma testing the addition of the alkylating agent temozolomide to standard radiotherapy. Determination of the methylation status of the MGMT promoter may become the first molecular diagnostic tool to identify patients most likely to respond that will allow individually tailored therapy in glioblastoma. To date, the test for the MGMT-methylation status is the only tool available that may direct the choice for alkylating agents in glioblastoma patients, but many others may hopefully become part of an arsenal to stratify patients to respective targeted therapies within the next years.

Diabetes and pre-diabetes are associated with cardiovascular risk factors and carotid/femoral intima-media thickness independently of markers of insuline resistance and adiposity

Background Impaired glucose regulation (IGR) is associated with detrimental cardiovascular outcomes such as cardiovascular disease risk factors (CVD risk factors) or intima-media thickness (IMT). Our aim was to examine whether these associations are mediated by body mass index (BMI), waist circumference (waist) or fasting serum insulin (insulin) in a population in the African region. Methods Major CVD risk factors (systolic blood pressure, smoking, LDL-cholesterol, HDL-cholesterol,) were measured in a random sample of adults aged 25-64 in the Seychelles (n=1255, participation rate: 80.2%). According to the criteria of the American Diabetes Association, IGR was divided in four ordered categories: 1) normal fasting glucose (NFG), 2) impaired fasting glucose (IFG) and normal glucose tolerance (IFG/NGT), 3) IFG and impaired glucose tolerance (IFG/IGT), and 4) diabetes mellitus (DM). Carotid and femoral IMT was assessed by ultrasound (n=496). Results Age-adjusted levels of the major CVD risk factors worsened gradually across IGR categories (NFG < IFG/NGT < IFG/IGT < DM), particularly HDL-cholesterol and blood pressure (p for trend <0.001). These relationships were marginally attenuated upon further adjustment for waist, BMI or insulin (whether considered alone or combined) and most of these relationships remained significant. With regards to IMT, the association was null with IFG/NGT, weak with IFG/IGT and stronger with DM (all more markedly at femoral than carotid levels). The associations between IMT and IFG/IGT or DM (adjusted by age and major CVD risk factors) decreased only marginally upon further adjustment for BMI, waist or insulin. Further adjustment for family history of diabetes did not alter the results. Conclusions We found graded relationships between IGR categories and both major CVD risk factors and carotid/femoral IMT. These relationships were only partly accounted for by BMI, waist and insulin. This suggests that increased CVD-risk associated with IGR is also mediated by factors other than the considered markers of adiposity and insulin resistance. The results also imply that IGR and associated major CVD risk factors should be systematically screened and appropriately managed.

Self-potentials in partially saturated media: the importance of explicit modeling of electrode effects

Self-potential (SP) data are of interest to vadose zone hydrology because of their direct sensitivity to water flow and ionic transport. There is unfortunately little consensus in the literature about how to best model SP data under partially saturated conditions, and different approaches (often supported by one laboratory data set alone) have been proposed. We argue that this lack of agreement can largely be traced to electrode effects that have not been properly taken into account. A series of drainage and imbibition experiments were considered in which we found that previously proposed approaches to remove electrode effects were unlikely to provide adequate corrections. Instead, we explicitly modeled the electrode effects together with classical SP contributions using a flow and transport model. The simulated data agreed overall with the observed SP signals and allowed decomposing the different signal contributions to analyze them separately. After reviewing other published experimental data, we suggest that most of them include electrode effects that have not been properly taken into account. Our results suggest that previously presented SP theory works well when considering the modeling uncertainties presently associated with electrode effects. Additional work is warranted to not only develop suitable electrodes for laboratory experiments but also to assure that associated electrode effects that appear inevitable in longer term experiments are predictable, so that they can be incorporated into the modeling framework.

De la Analítica al Social Media Intelligence : Una nueva oportunidad de liderar el mercado mediante una importante ventaja competitiva : saber identificar las necesidades del cliente en el Social Media : La reinvención de las investigaciones de mercado

La revolución que significó Internet a finales del siglo XX supone una oportunidad inmensa para el mundo corporativo. Con la aparición del Social Media y, en concreto, de las redes sociales, se han abierto un sinfín de nuevas oportunidades.No existe ningún otro invento que haya penetrado con tanta facilidad como lo han hecho estas plataformas; es el momento de que las empresas saquen provecho de ello.El objetivo principal de este proyecto consiste en identificar los beneficios potenciales para las empresas que conlleva actuar a través del Social Media. No contentos con eso, nos disponemos a mostrar las grandes razones por las que actuar: la posibilidad deidentificar las necesidades de tu público objetivo, huecos en el mercado y, por consiguiente, conseguir una ventaja competitiva clave en tu sector. ¿Cómo? La clave está en saber gestionar grandes volúmenes de información aplicando soluciones de inteligencia competitiva.Teniendo en cuenta que el proyecto gira entorno al Social Media, la estructura del mismo está dividida en dos grandes partes: en primer lugar estudiamos las claves de la investigación de mercados actual y, seguidamente, utilizamos una perspectiva más corporativa para mostrar las principales inquietudes que surgen en las empresas.Mediante ejemplos de casos prácticos muy relevantes, estudios que aporten datos clave y, sobre todo, las opiniones de profesionales del sector dentro y fuera de España, seremos capaces de deducir la importancia que tiene este terreno, así como el largo camino que nos queda a todos por delante.

A framework for hybrid simulations of two-phase flow in porous media

Rough a global coarse problem. Although these techniques are usually employed for problems in which the fine-scale processes are described by Darcy's law, they can also be applied to pore-scale simulations and used as a mathematical framework for hybrid methods that couples a Darcy and pore scales. In this work, we consider a pore-scale description of fine-scale processes. The Navier-Stokes equations are numerically solved in the pore geometry to compute the velocity field and obtain generalized permeabilities. In the case of two-phase flow, the dynamics of the phase interface is described by the volume of fluid method with the continuum surface force model. The MsFV method is employed to construct an algorithm that couples a Darcy macro-scale description with a pore-scale description at the fine scale. The hybrid simulations results presented are in good agreement with the fine-scale reference solutions. As the reconstruction of the fine-scale details can be done adaptively, the presented method offers a flexible framework for hybrid modeling.

La migració primaveral d'ocells als Aiguamolls de l'Empordà (Girona): primer anellament de Becadell Gros (Gallinago Media) a la Península Ibèrica

En aquest treball s'exposen els resultats obtinguts en la campanya 1994 d'anellament d'ocells inclosa dins del projecte italià Piccole Isole. Es demostra que el factor meteorològic afecta directament la fenologia migratòria de diferents espècies d'ocells. Es pretén també estudiar la influència dels diferents hàbitats en el nombre i en la diversitat de captures. Es recullen també en aquest treball les principals espècies visualitzades durant la campanya, com també l'elevat nombre de controls estrangers recuperats. Dintre de les captures i l'anellament posterior, destaca sobretot la d'un becadell gros (Gallinago media) fets per primera vegada a la peninsula Ibèrica

1.° Descriptio instrumenti cujusdam astronomici, quod Saphea vocatur : authore Joanne de Lineriis ; accedunt ejusdem canones. — 2.° Turketi tractatus, qui horizon dicitur, editus à Magistro Francone de Polonia ; sive liber de nominibus partium instrumenti astronomici, quod dicitur Turketus, et de ejusdem utilitatibus. — 3.° Opus cujus is est titulus : libri duo de motibus planetarum per instrumenta manualiter mota : hujusce operis initio haec antiqua manu annotata reperias ; Magister Henricus Arnault, Medicus Alemannus de Zuvolis, qui olim Divione domicilium elegit, superiorem litteram scripsit, et hunc librum suo labore compilavit, clarus scientia horologiorum ; qui in aede beati Stephani Divionensis sepultus media navi, plurimùm laudis sibi reliquit anno 1460. — 4.° Liber proportionum musicalium : authore Magistro Joanne de Muris, olim Canonico Parisiensi. — 5.° Philonis liber de ingeniis aquarum : finis desideratur.

Colbertinus