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The malaria parasite Plasmodium falciparum has a great capacity for evolutionary adaptation to evade host immunity and develop drug resistance. Current understanding of parasite evolution is impeded by the fact that a large fraction of the genome is either highly repetitive or highly variable and thus difficult to analyze using short-read sequencing technologies. Here, we describe a resource of deep sequencing data on parents and progeny from genetic crosses, which has enabled us to perform the first genome-wide, integrated analysis of SNP, indel and complex polymorphisms, using Mendelian error rates as an indicator of genotypic accuracy. These data reveal that indels are exceptionally abundant, being more common than SNPs and thus the dominant mode of polymorphism within the core genome. We use the high density of SNP and indel markers to analyze patterns of meiotic recombination, confirming a high rate of crossover events and providing the first estimates for the rate of non-crossover events and the length of conversion tracts. We observe several instances of meiotic recombination within copy number variants associated with drug resistance, demonstrating a mechanism whereby fitness costs associated with resistance mutations could be compensated and greater phenotypic plasticity could be acquired.

methods for the large-scale analysis of genetic variation in Plasmodium falciparum by deep sequencing of parasite DNA obtained from the blood of patients with malaria, either directly or after short-term culture. Analysis of 86,158 exonic single nucleotide polymorphisms that passed genotyping quality control in 227 samples from Africa, Asia and Oceania provides genomewide estimates of allele frequency distribution, population structure and linkage disequilibrium. By comparing the genetic diversity of individual infections with that of the local parasite population, we derive a metric of within-host diversity that is related to the level of inbreeding in the population. An open-access web application has been established for the exploration of regional differences in allele frequency and of highly differentiated loci in the P. falciparum genome. The genetic diversity and evolutionary plasticity of P. falciparum are major obstacles for malaria elimination. New forms of resistance against antimalarial drugs are continually emerging 1,2 , and new forms of antigenic variation are a critical point of vulnerability for future malaria vaccines. Effective tools are needed to detect evolutionary changes in the parasite population and to monitor the spread of genetic variants that affect malaria control. Here we describe the use of deep sequencing to analyse P. falciparum diversity, using blood samples from patients with malaria. The P. falciparum genome has several unusual features that greatly complicate sequence analysis, such as extreme AT bias, large tracts of nonunique sequence and several large families of intensely polymorphic genes 3 . Our aim was therefore not to determine the entire genome sequence of individual field samples—which would be prohibitively expensive with current technologies—but to define an initial set of single nucleotide polymorphisms (SNPs) distributed across the P. falciparum genome, whose genotype can be ascertained with confidence in parasitized blood samples by deep sequencing. An additional complication in the analysis of P. falciparum genome variation is that the billions of haploid parasites that infect a single individual can be a complex mixture of genetic types. Previous studies 4–8 have largely focused on laboratory-adapted parasite clones, but the within-host diversity of natural infections is of fundamental biological interest. Parasites in the blood replicate asexually, but when they are taken up in the blood meal of an Anopheles mosquito they undergo sexual mating. If the parasites in the blood are of diverse genetic types, this process of sexual mating can generate novel recombinant forms. Deep sequencing provides new ways of investigating within-host diversity and the role of sexual recombination in parasite evolution.

la segmentación es un proceso utilizado en visión artificial que consiste en dividir una escena en un conjunto de regiones, facilitando con ello la tarea de interpretación de una imagen. Los algoritmos de segmentación se basan en criterios como homogeneidad de la región y discontinuidad entre regiones disjuntas adyacentes. El presente artículo describe e implementa un modelo de segmentación que usa procesos de decisión estocásticos, el cual requiere apoyo y tiempo de computación para conseguir etiquetas óptimas, pero, entre otras ventajas, tiende a ser local y conduce a una implementación en hardware paralelo de manera natural.

A risk-adapted strategy based on all-trans retinoic acid (ATRA) and anthracycline monochemotherapy (PETHEMALPA99 trial) has demonstrated a high antileukemic efficacy in acute promyelocytic leukemia. We designed a new trial (LPA2005) with the objective of achieving stepwise improvements in outcome. Between July 2005 and April 2009, low- and intermediate-risk patients (leukocytes < 10 x 10(9)/L) received a reduced dose of mitoxantrone for the second consolidation course, whereas high-risk patients younger than 60 years of age received cytarabine combined with ATRA and idarubicin in the first and third consolidation courses. Of 372 patients attaining complete remission after ATRA plus idarubicin (92.5%), 368 proceeded to consolidation therapy. For low- and intermediate-risk patients, duration of neutropenia and thrombocytopenia and hospital stay were significantly reduced without sacrificing antileukemic efficacy, compared with the previous LPA99 trial. For high-risk patients, the 3-year relapse rate was significantly lower in the LPA2005 trial (11%) than in the LPA99 (26%; P = .03). Overall disease-free survival was also better in the LPA2005 trial (P = .04). In conclusion, the lower dose of mitoxantrone resulted in a significant reduction of toxicity and hospital stay while maintaining the antileukemic activity, and the combination of ATRA, idarubicin, and cytarabine for high-risk acute promyelocytic leukemia significantly reduced the relapse rate in this setting. Registered at http://www.clinicaltrials.gov as NCT00408278. (Blood. 2010; 115(25):5137-5146)

Introducción: La traqueostomía descrita ya hacia el 1500 AC, en las últimas décadas ha evolucionado al desarrollo de sistemas de abordaje mínimamente invasivos o percutáneos, de los cuales la técnica de Ciaglia Blue Rhino (dilatador único), es la más utilizada en la actualidad. Objetivo: Se realizó un estudio retrospectivo descriptivo de las traqueostomías realizadas en el Hospital Clínico FUSAT de Rancagua, entre los años 2006 y 2012, con el fin de evaluar ventajas, desventajas e incidencia de complicaciones de la técnica abierta versus la técnica percutánea en nuestras manos. Material y método: Se incluyeron 64 traqueostomías consecutivas de las cuales 42 fueron percutáneas con técnica de Ciaglia Blue Rhino y el resto con técnica abierta clásica. Resultados: Al analizar los resultados encontramos ventajas de la técnica percutánea como un importante acortamiento del tiempo quirúrgico (de 45,27 minutos en la técnica clásica a 15,28 minutos promedio en la técnica percutánea), una menor incidencia de complicaciones (14% en procedimiento percutáneo versus 27% en procedimiento abierto) y una curva de aprendizaje relativamente rápida que permitió que la indicación para el procedimiento percutáneo pasara desde 68% en la primera mitad de la serie al 92% en la segunda mitad de ésta. Conclusión: Creemos que la técnica es segura en manos de otorrinolaringólogos y debería incorporarse como una herramienta más al arsenal quirúrgico de la especialidad. Introduction: The tracheostomy described as about 1500 BC, only in recent decades has seen the development of systems for minimally invasive or percutaneous, of which the Ciaglia Blue Rhino technique (single dilator), is most often used today. Aim: We performed a retrospective study of tracheostomies performed at the FUSAT Clinical Hospital from Rancagua, between 2006 and 2012, in order to evaluate advantages, disadvantages and incidence of complications of open surgery versus percutaneous technique in our hands. Material and methods: Included 64 tracheostomies of which 42 were percutaneous Ciaglia Blue Rhino technique. Results: In analyzing the results highlights shortening surgical time from 45.27 minutes for classical technique to 15.28 minutes for percutaneous (statistically significant) in relation to complications, they showed a lower incidence in the group with percutaneous technique, the learning curve of the procedure is quick, reaching its indication in our series more than 90% of cases once acquired experience. Conclusion: We believe that the technique is safe in the hands of Otolaryngologists and should be incorporated as another tool to the arsenal surgical specialty.

2014AbstractA new type of bioceramic has been designed and obtained within the sub-system Ca2SiO4–7CaOP2O52SiO2. The selected composition wasthat corresponding to the eutectoid point 69 wt% dicalcium silicate–31 wt% tricalcium phosphate. Sintering behavior, phase evolution andmicrostructural changes were analyzed by XRD and SEM. Bio-reactivity was determined by immersion of materials in simulated body fluid forseveral periods of time as well as studies in human adipose stem cells (hASC). The investigated materials are bio-acceptable since no toxic or otherharmful evidence was detected. A carbonated hydroxyapatite was formed on the surface of the 31R material within 3 days. Cell attachment assayshowed that the ceramics supported the hASC cells adhesion and spreading, and the cells established close contacts with the ceramics after 24 h ofculture. The influence of the microstructure (porosity, grain size and phase composition) on the in vitro behavior of the obtained bioceramics wasalso examined.

We report citrin deficiency in a neonatal non-East-Asian patient, the ninth Caucasian reported with this disease. The association of intrahepatic cholestasis, galactosuria, very high alpha-fetoprotein and increased plasma and urine citrulline, tyrosine, methionine and threonine levels suggested citrin deficiency. Identification of a protein-truncating mutation (c.1078C>T; p.Arg360*) in the SLC25A13 gene confirmed the diagnosis. An immediate response to a high-protein, lactose-free, low-carbohydrate formula was observed. Our report illustrates the need for awareness on citrin deficiency in Western countries.

The geographic information required to implement precision viticulture applications in real fields has led to the extensive use of remote sensing and airborne imagery. While advantageous because they cover large areas and provide diverse radiometric data, they are unreachable to most of medium-size Spanish growers who cannot afford such image sourcing. This research develops a new methodology to generate globally-referenced vigor maps in vineyards from ground images taken with a camera mounted on a conventional tractor. This monocular camera was able to sense in the visible, NIR, and UV spectra, selectively isolated with bandpass filters. The versatility of the system was further enhanced by implementing two sampling levels: intensive coverage of 1 m2 and super-intensive for 0.1 m2. The core of the procedure resides in the algorithm for automatically segmenting the filtered images in such a way that relative differences in canopy vigor were objectively quantified. The calculation of the dynamic threshold involved the mathematical concepts of gradient and curvature. Field results showed that relative differences in vine vigor can be detected from NIR-filtered images and intensive sampling. Furthermore, individual images were successfully merged into a global vigor map that can be directly employed by end-users. Super-intensive sampling and UV perception were not appropriate for building vigor maps, but could be of interest for other agronomical purposes as the early detection of diseases. Field tests proved the feasibility of building global vigor maps from ground-based imagery, and showed the potential of this technique as a predictive instrument for modest-size producers., La información requerida para implementar aplicaciones de viticultura de precisión en parcelas reales ha desembocado en el uso extensivo de la teledetección y la detección aérea. Si bien estos métodos son ventajosos por cubrir vastas áreas y proveer diversa información radiométrica, suelen ser inalcanzables para el productor español medio debido a los gastos ocasionados. Esta investigación desarrolla una nueva metodología para generar mapas de vigor con referencias globales basados en imágenes digitales tomadas con una cámara montada sobre un tractor convencional y con capacidad para percibir en el espectro visible, infrarrojo cercano (NIR) y ultravioleta (UV). Para hacer el sistema más versátil se analizaron dos niveles de muestreo: intensivo (1 m2 de cobertura vegetal) y super-intensivo (0,1 m2 de cobertura). El núcleo de la metodología propuesta se basa en el algoritmo de segmentación de imágenes para cuantificar automáticamente diferencias en vigor vegetativo. El cálculo del umbral dinámico se fundamenta en los conceptos matemáticos de gradiente y curvatura. Los resultados obtenidos mostraron que es posible cuantificar diferencias en vigor vegetativo de viñas utilizando el rango espectral del NIR con un muestreo intensivo. El muestreo super-intensivo y la banda espectral UV no resultaron adecuados para esta aplicación, aunque pueden aportar información clave en otras aplicaciones agronómicas. Las pruebas de campo demostraron la viabilidad de generar mapas georreferenciados de vigor desde vehículos convencionales, y mostraron el potencial de esta técnica como instrumento predictivo para explotaciones de tamaño medio.

54 p., 9 figures, 1 table and bibliography The melanocortin 4 receptor (MC4R) is a G-protein coupled receptor mainly expressed in the central nervous system of vertebrates. Activation of the MC4R leads to a decrease in food intake, while inactivating mutations are a genetic cause of obesity. The binding of agoutirelated protein (AGRP) reduces agonist-stimulated cAMP production (competitive antagonist) but also the basal activity of the receptor, as an inverse agonist. Transgenic zebrafish overexpresing AGRP display increased food intake and linear growth, indicative of a physiological role for the melanocortin system in the control of the energy balance in fish. We report on the cloning, pharmacological characterization, tissue distribution and detailed brain mapping of a sea bass (Dicentrarchus labrax) MC4R orthologue. Sea bass MC4R is profusely expressed within food-intake controlling pathways of the fish brain. However, the activity of the melanocortin system during progressive fasting does not depend on the hypothalamic/pituitary proopiomelanocortin (POMC) and MC4R expression, which suggests that sea bass MC4R is constitutively activated and regulated by AGRP binding. We demonstrate that AGRP acts as competitive antagonist and reduces MTII-induced cAMP production. AGRP also decreases the basal activity of the receptor as an inverse agonist. This observation suggests that MC4R is constitutively active and supports the evolutionary conservation of the AGRP/MC4R interactions. The inverse agonism, but not the competitive antagonism, depends on the presence of a phosphodiesterase inhibitor (IBMX). This suggests that inverse agonism and competitive antagonism operate through different intracellular signalling pathways, a view that open up new targets for the treatment of melanocortininduced metabolic syndrome. VCR was recipient of a postdoctoral fellowship from “Fundación Séneca” and “Agencia Regional de Ciencia y Tecnología” (Science and Technology Plan for CARM 2003-2006, Séneca Program 2004). Funded by AGL2004-08137-C04-04; AGL2007-65744-C03-02; CSD 2007-00002 to JM C-R and NIH/DK64265 to GM.

The current study examines whether the fear of being laughed at (gelotophobia) can be assessed reliably and validly by means of a self-report instrument in different countries of the world. All items of the GELOPH (Ruch and Titze, GELOPH〈46〉, University of Düsseldorf, 1998; Ruch and Proyer, Swiss Journal of Psychology 67:19–27, 2008b) were translated to the local language of the collaborator (42 languages in total). In total, 22,610 participants in 93 samples from 73 countries completed the GELOPH. Across all samples the reliability of the 15-item questionnaire was high (mean alpha of .85) and in all samples the scales appeared to be unidimensional. The endorsement rates for the items ranged from 1.31% through 80.00% to a single item. Variations in the mean scores of the items were more strongly related to the culture in a country and not to the language in which the data were collected. This was also supported by a multidimensional scaling analysis with standardized mean scores of the items from the GELOPH〈15〉. This analysis identified two dimensions that further helped explaining the data (i.e., insecure vs. intense avoidant-restrictive and low vs. high suspicious tendencies towards the laughter of others). Furthermore, multiple samples derived from one country tended to be (with a few exceptions) highly similar. The study shows that gelotophobia can be assessed reliably by means of a self-report instrument in cross-cultural research. This study enables further studies of the fear of being laughed at with regard to differences in the prevalence and putative causes of gelotophobia in comparisons to different cultures.

Se describen técnicamente así como los resultados de los siguientes ensayos: Variedades verdes de espárrago Variedades blancas de espárrago. Tallos Madres Técnicas Macrotunel

[ES] La industria papelera proporciona un gran volumen de residuos de lodos de papel que se han empleado en la producción de cementos puzolánicos (Silva y Glasser, 1990; Frías et al., 2000). Se han determinado las condiciones térmicas y de estancia en el horno en las que se deben tratar estos lodos para obtener una máxima actividad puzolánica, estableciéndose que estos parámetros son 7004C y 2 horas de permanencia (Frías et al., 2005). Empleando estos lodos calcinados se ha seguido un estudio de intemperancia ante dos situaciones: fenómenos de niebla salina y de hielo/deshielo, exponiendo los cementos a las condiciones ambientales de costa (Guernica, Vizcaya) y de continentalidad (Madrid). En ambos casos se han realizado estudios morfológicos de los materiales presentes en las muestras y de difusión de iones a través de las probetas expuestas a las diferentes condiciones climatológicas Los estudios que se han realizado han sido por microscopía electrónica de barrido (SEM-EDX) y Difracción de Rayos X (DRX).

Descripción técnica de los resultados de los siguientes ensayos: 1. Variedades verdes de espárrago 2. Variedades blancas de espárrago. 3. Tallos Madres 4. Técnicas con macrotunel 5. Riego localizado enterrado y superficial. 6. Control de adventicias con escarda química.