Protective effects of zoledronate after denosumab discontinuation

RESUMEN : Tras suspender el tratamiento con denosumab se produce un aumento de los marcadores bioquímicos de remodelado óseo por encima de los valores de partida, conocido como “efecto rebote”. Este se acompaña de una disminución de la densidad mineral ósea (DMO) y un aumento del riesgo de fracturas vertebrales, especialmente fracturas vertebrales múltiples. Se ha sugerido que la administración de fármacos antirresortivos podría prevenir este efecto rebote. Por tanto, hemos considerado importante verificar que la administración de antirresortivos tras la suspensión de denosumab previene realmente el incremento de los marcadores de remodelado óseo. Describimos los casos de trece pacientes con osteoporosis que habían recibido denosumab durante más de cuatro años. Aproximadamente 6 meses después de la última inyección de denosumab recibieron una infusión intravenosa de 5 mg de ácido zoledrónico, fármaco escogido por su elevada potencia y su posología. Fueron seguidos durante un periodo de dos años, en el que ninguno presentó fracturas clínicas. Además, ningún valor de CTX ni la DMO en la columna lumbar sobrepasó su nivel basal correspondiente en ningún momento. Por tanto, como resultado de nuestro estudio, podemos decir que una infusión de zoledronato tras la suspensión de denosumab parece prevenir adecuadamente el fenómeno rebote.ABSTRACT : Discontinuation of denosumab results in a marked increase in bone turnover markers (BTM) above baseline, known as “rebound phenomenon”. This is accompanied by a decrease in bone mineral density (BMD) and an increase in the risk of vertebral fractures, particularly multiple vertebral fractures. It has been suggested that the administration of antiresorptive drugs could prevent the turnover rebound. Therefore, we have considered important to verify that the administration of antiresorptives after denosumab discontinuation certainly prevents the rebound of BTM. We report here a case series of thirteen patients with osteoporosis who had received denosumab for more than four years. Approximately 6 months after the last denosumab injection, they were given a single infusion of zoledronate (5 mg), drug chosen due to its potency and posology. They were followed-up for over a two-year period, in which none of them presented any clinical fractures. Furthermore, no single value of CTX nor lumbar spine BMD surpassed their corresponding baseline at any time. So, as a result of our study we can confirm that an injection of zoledronate at denosumab discontinuation seems to adequately prevent the rebound phenomenon.Grado en Medicin

Validación de las alturas de un plan de vuelo

El objetivo de este trabajo consiste en verificar un plan de vuelo de un UAV (Unmanned Aerial Vehicle) contra posibles colisiones que se puedan producir con el nivel del terreno y teniendo en cuenta que no puede entrar en el espacio aéreo controlado. Para poder verificarlo se analizan los diferentes requisitos propuestos por el usuario, e.g: detectar posibles conflictos del plan de vuelo propuesto, la presencia de márgenes de seguridad, el formato de los datos de la altura del cartográfico, etc. También, se informará al usuario de la altura mínima obtenida en un flight plan completo, ya que será la altura más crítica que adquirirá el avión en todo su recorrido. El avión tendrá especificado un flight plan en el cual podrá realizar dos tipos de trayectorias diferentes (LEGs). La primera consiste en una línea recta (Trackto- Fix) y la segunda en un arco de circunferencia (Radius-to-Fix). Los datos de entrada de la aplicación, que verificará el plan de vuelo, estarán compuestos por un conjunto de matrices de alturas (cada matriz corresponde a la elevación del terreno por el que pasa un LEG propuesto) y los datos de cada LEG. En ambos tipos de LEGs será necesario conocer la posición inicial y final, así como la altura en dichas posiciones, y en el caso del Radius-to-Fix, además de los datos anteriores, se necesitará el centro y el sentido de giro (clockwise o anticlockwise). La implementación de las trayectorias anteriores se ha realizado mediante dos algoritmos que identifican las posiciones por las que volará el avión y así comprobar el principal objetivo, es decir, que no se produzca una colisión. La aplicación analizará cada uno de los LEGs y comprobará si es seguro (no hay colisión y no entra en espacio aéreo controlado). Si el flight plan es correcto se informará de la altura mínima obtenida por el avión en todo el trayecto. Si no es correcto se informará que el plan de vuelo es erróneo

Multiple macroevolutionary routes to becoming a biodiversity hotspot.

Why is species diversity so unevenly distributed across different regions on Earth? Regional differences in biodiversity may stem from differences in rates of speciation and dispersal and colonization times, but these hypotheses have rarely been tested simultaneously at a global scale. Our study reveals the macroevolutionary routes that have generated hotspots of mammal and bird biodiversity by analyzing the tempo and mode of diversification and dispersal within major biogeographic realms. Hotspots in tropical realms had higher rates of speciation, whereas those in temperate realms received more immigrant species from their surrounding regions. We also found that hotspots had higher spatial complexity and energy availability, providing a link between the environment and macroevolutionary history. Our study highlights how assessing differences in macroevolutionary history can help to explain why biodiversity varies so much worldwide

Novel intron markers to study the phylogeny of closely related mammalian species

BACKGROUND: Multilocus phylogenies can be used to infer the species tree of a group of closely related species. In species trees, the nodes represent the actual separation between species, thus providing essential information about their evolutionary history. In addition, multilocus phylogenies can help in analyses of species delimitation, gene flow and genetic differentiation within species. However, few adequate markers are available for such studies. RESULTS: In order to develop nuclear markers that can be useful in multilocus studies of mammals, we analyzed the mammalian genomes of human, chimpanzee, macaque, dog and cow. Rodents were excluded due to their unusual genomic features. Introns were extracted from the mammalian genomes because of their greater genetic variability and ease of amplification from the flanking exons. To an initial set of more than 10,000 one-to-one orthologous introns we applied several filters to select introns that belong to single-copy genes, show neutral evolutionary rates and have an adequate length for their amplification. This analysis led to a final list of 224 intron markers randomly distributed along the genome. To experimentally test their validity, we amplified twelve of these introns in a panel of six mammalian species. The result was that seven of these introns gave rise to a PCR band of the expected size in all species. In addition, we sequenced these bands and analyzed the accumulation of substitutions in these introns in five pairs of closely related species. The results showed that the estimated genetic distances in the five species pairs was quite variable among introns and that this divergence cannot be directly predicted from the overall intron divergence in mammals. CONCLUSIONS: We have designed a new set of 224 nuclear introns with optimal features for the phylogeny of closely related mammalian species. A large proportion of the introns tested experimentally showed a perfect amplification and enough variability in most species, indicating that this marker set can be very helpful in multilocus phylogenetics of mammals. Due to the lower variability and stronger stochasticity of nuclear markers with respect to mitochondrial genes, studies should be designed to make use of several markers like the ones designed here

Francisco Giner de los Ríos o el arte de forjar almas

Este trabajo tiene por objeto dibujar el perfil educador de Francisco Giner de los Ríos, el hombre más carismático de la Institución Libre de Enseñanza. Apoyándonos sobre todo en el testimonio escrito de algunos de sus discípulos más cualificados, estas páginas reflejan la actividad de un maestro universitario a pie de obra. Giner superó el horizonte de su época porque se opuso al memorismo estéril y construía el saber con sus discípulos, planteando problemas e invitando a encontrar soluciones. Era, en definitiva, un educador moderno, de corte europeo. Y lo era allá donde estuviera; por eso, con su buen hacer pero, sobre todo, con su ser, iluminó una herencia pedagógica de cuatro décadas, ya en el siglo XX. Que a los educadores de hoy, bien entrado el XXI, nos sirva para reforzar nuestra responsabilidad y redoblar esfuerzos en la tarea, seguramente, más comprometida que existe.The aim of these lines is to present the portrait of the most charismatic educator of the Institución Libre de Enseñanza: Francisco Giner de los Ríos. Building our discourse on the written testimony of some of his most qualified disciples, these pages show the activity of a university teacher —not just a professor—. Giner exceeded the horizon of his time because he opposed the sterile memorization and built knowledge with his disciples, not only proposing problems but also inviting them to solve them. In short, he was a modern educator who was aware of the European way of teaching. And he was all these things regardless of the place where he was. Therefore, with his savoir faire, but above all thanks to his great way of being, he lit a pedagogical legacy of four decades within the twentieth century. His life may be a good mirror in which educators could see their duties and efforts reflected

Dead Zone Accretion Flows in Protostellar Disks

Planets form inside protostellar disks in a dead zone where the electrical resistivity of the gas is too high for magnetic forces to drive turbulence. We show that much of the dead zone nevertheless is active and flows toward the star while smooth, large-scale magnetic fields transfer the orbital angular momentum radially outward. Stellar X-ray and radionuclide ionization sustain a weak coupling of the dead zone gas to the magnetic fields, despite the rapid recombination of free charges on dust grains. Net radial magnetic fields are generated in the magneto-rotational turbulence in the electrically conducting top and bottom surface layers of the disk, and reach the midplane by Ohmic diffusion. A toroidal component to the fields is produced near the midplane by the orbital shear. The process is similar to the magnetization of the Solar tachocline. The result is a laminar, magnetically-driven accretion flow in the region where the planets form.Comment: 12 pages, 4 figure