Estudio de factores moleculares predictores de respuesta a IMATINIB en pacientes diagnósticados de leucemia mieloide crónica en fase crónica

La leucemia mieloide crónica (LMC) es una enfermedad clonal originada en la célula madre totipotente hematopoyética, caracterizada por la translocación de los brazos largos de los cromosomas 9 y 22, y que da lugar al gen de fusión BCR-ABL1. En 1996 se reporta la gran eficacia in-vitro del compuesto STI571 y en 2003 se publican los resultados del estudio IRIS. Los resultados de este estudio suponen un hito en la historia de la LMC y, por extensión, del tratamiento de la patología tumoral. Posteriormente, dasatinib y nilotinib fueron también aprobados para su uso en primera línea. De los 3 inhibidores de tirosinkinasa (ITK) disponibles en primera línea, imatinib parece ser el de uso más extendido por la buena respuesta de la mayoría de los pacientes y por la mayor experiencia de uso que se tiene con el mismo, durante la cual no se han desarrollado efectos secundarios severos. No obstante, en torno al 25% de los pacientes requerirá el uso de los ITK de segunda generación por falta de eficacia de imatinib. En la LMC hay 3 scores clínicos: Sokal, Hasford y EUTOS. Ninguno de los cuales está claramente recomendado para dirigir la terapia de primera línea, aunque la clasificación en el grupo de alto riesgo en cualquiera de ellos podría apoyar el uso de los ITK de segunda generación, al ser considerado una alarma por la ELN. Se han desarrollado diversos estudios comparando el perfil de expresión génica de pacientes respondedores frente a no respondedores a imatinib pese a lo cual actualmente no se aplica ningún test molecular al diagnóstico que ayude a predecir la respuesta a imatinib. Por lo tanto, la mejor manera de saber la respuesta del paciente a los ITK es valorando esta, una vez iniciado el tratamiento y la tendencia es a hacerlo lo antes posible para llevar a cabo un cambio de línea precoz. Parece razonable pensar que sería incluso más beneficioso saber, antes de iniciar el tratamiento, las probabilidades de respuesta al mismo para comenzar desde el inicio con el ITK adecuado..

Refrigerador doméstico con efecto Peltier, acumuladores térmicos y termosifones evaporativos

Referencia OEPM: P9801016.-- Fecha de solicitud: 14/05/1998.-- Titular: Consejo Superior de Investigaciones Científicas (CSIC).La patente se refiere a instalaciones frigoríficas que funcionan gracias a la combinación de elementos productores de efecto Peltier y termosifones con cambio de fase líquido-vapor. Básicamente consta de: 1) Recinto de refrigeración. 2) Disipador de calor. 3) Un circuito cerrado y estanco conteniendo un fluido, que hierve o se evapora. 4) Elementos de efecto Peltier (primera etapa). 5) Termosifón que transporta el calor, a las caras frías de las pastillas de efecto Peltier de la primera etapa. 6) Termosifón que intercambia el calor con el anterior y transporta éste de las caras calientes de las pastillas Peltier de la segunda etapa. 7) Elementos de efecto Peltier (segunda etapa). 8) Termosifón que transporta el calor, del recinto a baja temperatura, a las caras frías de las placas Peltier de la segunda etapa.Peer reviewe

Modernización de equipo feedback MS-150 para el aprendizaje activo en ingeniería de control

[Resumen] En este artículo se presenta el desarrollo e integración de elementos hardware para construir un sistema de adquisición de datos que permite modernizar el equipo didáctico Feedback MS-150 con el fin de ampliar su tiempo de vida y aumentar el alcance de los conceptos de control que se pueden explicar con él. El sistema de adquisición no supera los 100 €

Flint and Quartzite: Distinguishing Raw Material Through Bone Cut Marks

Since the 1980s, several experimental analyses have been able to differentiate some lithic tool types and some of their raw materials according to the morphology of cut marks imprinted by such tools when used for butchering activities. Thus, metal tool use has been differentiated in contexts with an abundance of lithic tools, or even the use of hand axes has been documented in carcass processing, in contrast with simple unretouched or retouched flakes. As important as this information is, there are still other important aspects to be analysed. Can cut marks produced with different lithic raw material types be differentiated? Can cut marks made with different types of the same raw material type be characterized and differentiated? The objective of this study is to evaluate if cut marks resulting from the use of different flints and different quartzites are distinguishable from each other. In the present work, an experimental analysis of hundreds of cut marks produced by five types of flint and five varieties of quartzite was carried out. Microphotogrammetry and geometric–morphometric techniques were applied to analyse these cut marks. The results show that flint cut marks and quartzite cut marks can be characterized at the assemblage level. Different types of flint produced cut marks that were not significantly different from each other. Cut marks made with Olduvai Gorge quartzite were significantly different from those produced with a set comprising several other types of quartzites. Crystal size, which is larger in Olduvai Gorge quartzites (0.5 mm) than Spanish quartzites (177–250 μm), is discussed as being the main reason for these statistically significant differences. This documented intra-sample and inter-sample variance does not hinder the resolution of the approach to differentiate between these two generic raw material types and opens the door for the application of this method in archaeological contexts

Advanced monitoring of rail breakage in double-track railway lines by means of PCA techniques

This work describes a classifier designed to identify rail breakages in double-track railway lines, completing the electronic equipment carried out by authors. The main objective of this proposal is to guarantee the integrity of tracks before the railway traffic starts working. In addition, it facilitates maintenance tasks providing information about possible breakages. The detection of breakages is based on the analysis of eight currents provided by the electronic equipment, one per rail, at the ends of the section (emitting and receiving nodes). The imbalance that occurs among the value of these currents implies that there is at least a breakage in the track section under analysis. This analysis is conducted according to three phases. The first one identifies whether there is a breakage, and, in that case, the damaged track is identified. The second phase provides information about which rail is broken (internal, external or both of them) in the previously identified track. Finally, if there is only one breakage, the third phase estimates its most likely zone along the track section. This situation is considered as a classification problem, and solved by means of the Principal Component Analysis technique. This means that a significant number of measurements is required for every breakage pattern (types of breakages) to be considered. Due to the difficulty of having real data, the proposal has been validated using an 8km-long double-track hardware simulator specially designed by the authors, with specific localizations for breakages

Clinical impact of acute kidney injury on short- and long-term outcomes after transcatheter aortic valve implantation with the CoreValve prosthesis

AbstractBackgroundAcute kidney injury (AKI) after cardiac surgery is associated with increased mortality, but few data exist on the occurrence and clinical impact of AKI associated with transcatheter aortic valve implantation (TAVI). The objective of this study was to determine the incidence and prognosis of AKI after percutaneous implantation of the CoreValve® (Medtronic, Minneapolis, MN, USA) prosthesis.MethodsA total of 357 patients with severe aortic stenosis and 9 patients with pure native aortic regurgitation were treated with the CoreValve prosthesis. AKI was defined according to Valve Academic Research Consortium criteria as the absolute increase in serum creatinine ≥0.3mg/dl at 72h post percutaneous procedure.ResultsAKI was identified in 58 patients (15.8%), none of whom required renal replacement therapy. In patients with AKI, the mortality at 30 days was 13.5% compared with 1.6% of patients without AKI, [odds ratio (OR)=12.2 (95% CI 3.53–41.9); p<0.001] and total mortality after a mean of 26.2±17 months was 29.3% vs. 14.9% [OR=2.36 (95% CI 1.23–4.51), p=0.008]. In the multivariate analysis, AKI was an independent predictor of cumulative total mortality [hazard ratio=2.151, (95% CI from 1.169 to 3.957), p=0.014].ConclusionsThe deterioration of renal function in patients undergoing TAVI with the CoreValve prosthesis is a serious and frequent complication. The occurrence of AKI was associated with increased early mortality and was also a predictor of worse outcomes in follow-up

Thawing boar semen in the presence of seminal plasma improves motility, modifies subpopulation patterns and reduces chromatin alterations

P. 1576-1584Seminal plasma could have positive effects on boar semen after thawing. In the present study we investigated changes in the motility and chromatin structure in spermatozoa over 4 h incubation (37°C) of boar semen thawed in the presence of 0%, 10% or 50% seminal plasma from good-fertility boars. Cryopreserved doses were used from seven males, three of which were identified as susceptible to post-thawing chromatin alterations. Motility was analysed by computer-aided sperm analysis every hour, and data were used in a two-step clustering, yielding three subpopulations of spermatozoa (slow non-linear, fast non-linear, fast linear). Chromatin structure was analysed using a sperm chromatin structure assay and flow cytometry to determine the DNA fragmentation index (%DFI) as a percentage, the standard deviation of the DFI (SD-DFI) and the percentage of high DNA stainability (%HDS), indicating chromatin compaction. Thawing without seminal plasma resulted in a rapid loss of motility, whereas seminal plasma helped maintain motility throughout the incubation period and preserved the subpopulation comprising fast and linear spermatozoa. The incidence of chromatin alterations was very low in samples from non-susceptible males, whereas samples from males susceptible to post-thawing chromatin alterations exhibited marked alterations in %DFI and %HDS. Seminal plasma partly prevented these alterations in samples from susceptible males. Overall, 50% seminal plasma was the most efficient concentration to protect motility and chromatin. Some changes were concomitant with physiological events reported previously (e.g., semen thawed with 50% seminal plasma increased the production of reactive oxygen species and yielded higher fertility after AI). Thawing in the presence of seminal plasma could be particularly useful in the case of samples susceptible to post-thawing chromatin damage.S

LOCATE-US: Indoor Positioning for Mobile Devices Using Encoded Ultrasonic Signals, Inertial Sensors and Graph- Matching

Indoor positioning remains a challenge and, despite much research and development carried out in the last decade, there is still no standard as with the Global Navigation Satellite Systems (GNSS) outdoors. This paper presents an indoor positioning system called LOCATE-US with adjustable granularity for use with commercial mobile devices, such as smartphones or tablets. LOCATE-US is privacy-oriented and allows every device to compute its own position by fusing ultrasonic, inertial sensor measurements and map information. Ultrasonic Local Positioning Systems (ULPS) based on encoded signals are placed in critical zones that require an accuracy below a few decimeters to correct the accumulated drift errors of the inertial measurements. These systems are well suited to work at room level as walls confine acoustic waves inside. To avoid audible artifacts, the U-LPS emission is set at 41.67 kHz, and an ultrasonic acquisition module with reduced dimensions is attached to the mobile device through the USB port to capture signals. Processing in the mobile device involves an improved Time Differences of Arrival (TDOA) estimation that is fused with the measurements from an external inertial sensor to obtain real-time location and trajectory display at a 10 Hz rate. Graph-matching has also been included, considering available prior knowledge about the navigation scenario. This kind of device is an adequate platform for Location-Based Services (LBS), enabling applications such as augmented reality, guiding applications, or people monitoring and assistance. The system architecture can easily incorporate new sensors in the future, such as UWB, RFiD or others.Universidad de AlcaláJunta de Comunidades de Castilla-La ManchaAgencia Estatal de Investigació

Diversidad genética en burros criollos de México

The aim of this study was to evaluate the genetic diversity of the Mexican criollo donkey with SNP-type genetic markers. Sixteen individuals (eight males and eight females) were randomly sampled and genotyped using the GGP Equine 70K chip (71 947 loci). Within chromosome the polymorphic SNPs were identified, determining the expected (He) and observed (Ho) heterozygosity, polymorphic information content (PIC), the fixation index (FIS) and the Hardy-Weinberg equilibrium (HW). Linkage disequilibrium was assessed based on the correlation (r2) between frequencies across loci. An analysis of molecular variance (AMOVA) and a cluster study were performed to infer the number of clusters (k). It was found that 3579 loci (4.9%) presented genetic variability, but 24.9% presented HW disequilibrium (p&lt;0.05). Across chromosomes, the number of polymorphic loci ranged from 50 to 269 with a mean of 115. The (within chromosome) means for PIC and FIS ranged from 0.222 to 0.267 and -0.392 to -0.208, respectively. In all chromosomes Ho was superior to He. For r2, the mean values within chromosome were greater than 0.10; the optimal k corresponded to 2. In the AMOVA, the genetic variability within individuals explained 67%. The SNPs identified as polymorphic make up a first panel of genetic markers for the Mexican creole burro, and the estimated genetic variability can be used in development and conservation schemes.El estudio tuvo como objetivo evaluar la diversidad genética del burro criollo mexicano con marcadores genéticos de tipo SNP. Se muestreó aleatoriamente a 16 individuos (ocho machos y ocho hembras) y el genotipado se hizo con el chip GGP Equine 70K (71 947 loci). Dentro de cromosoma se identificaron los SNP polimórficos, determinándose la heterocigosis esperada (He) y observada (Ho), contenido de información polimórfica (CIP), el índice de fijación (FIS) y el equilibrio (HW) Hardy-Weinberg. El desequilibrio de ligamiento se evaluó con base en la correlación (r2) entre frecuencias a través de locus. Se realizó un análisis de varianza molecular (AMOVA) y un estudio de agrupamiento para inferir el número de cluster (k). Se encontró que 3579 loci (4.9%) presentaron variabilidad genética, pero el 24.9% presentó desequilibrio HW (p&lt;0.05). A través de cromosomas, el número de loci polimórficos osciló de 50 a 269 con un promedio de 115. Los promedios (dentro de cromosoma) para PIC y FIS fluctuaron de 0.222 a 0.267 y de -0.392 a -0.208, respectivamente. En todos los cromosomas Ho fue superior a He. Para r2, los valores promedio dentro de cromosoma fueron superior a 0.10; el k óptimo correspondió a 2. En el AMOVA, la variabilidad genética dentro de individuos explicó el 67%. Los SNP identificados como polimórficos, conforman un primer panel de marcadores genéticos para el burro criollo mexicano, y la variabilidad genética estimada puede ser utilizada en esquemas de desarrollo y conservación