999 resultados para Burr, Aaron, 1716-1757


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En el presente trabajo se analiza el origen del almudí de Lérida –mercado de granos de la ciudad, su funcionamiento y su papel en el territorio. En base a la mercurial de Lérida, hemos elaborado una nueva serie de los precios del trigo siguiendo el año agrícola y utilizando cinco mercados, uno por semana. Finalmente, se presenta un primer estudio comparativo para el periodo 1757/58-1807/08 entre estos precios de Lérida y los de Barcelona, elaborados con la misma metodología. Las fuentes principales son los registros de precios y las actas del ayuntamiento de Lérida. Los precios del almudí serán un referente para el conjunto de la Cataluña occidental y el Aragón oriental. A pesar de que el mercado de Lérida está poco regulado, en los momentos de crisis de la segunda mitad del siglo XVIII y en el primer tercio de la siguiente centuria, la municipalidad realiza diversas acciones a favor de los vecinos más necesitados. Estas iniciativas nos remiten a la economía moral. Si bien los nuevos precios de Lérida son, en general, muy similares a los equivalentes realizados con el mercado central del mes, las diferencias son muy significativas para determinados momentos críticos. Este hecho confirma la necesidad de elaborar precios de mayor calidad para los diferentes mercados catalanes y españoles. Finalmente, la comparación de los precios de Lérida y Barcelona del período 1777/78-1807/08 con 1757/58-1776/77, permite confirmar que las coyunturas críticas del último tercio del siglo XVIII y comienzos del siglo XIX provocan respuestas de los diferentes agentes económicos de la Cataluña occidental que retrasan temporalmente la transferencia de la información que reflejan los precios de Barcelona a los precios del almudí de Lérida.

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There is a widespread agreement from patient and professional organisations alike that the safety of stem cell therapeutics is of paramount importance, particularly for ex vivo autologous gene therapy. Yet current technology makes it difficult to thoroughly evaluate the behaviour of genetically corrected stem cells before they are transplanted. To address this, we have developed a strategy that permits transplantation of a clonal population of genetically corrected autologous stem cells that meet stringent selection criteria and the principle of precaution. As a proof of concept, we have stably transduced epidermal stem cells (holoclones) obtained from a patient suffering from recessive dystrophic epidermolysis bullosa. Holoclones were infected with self-inactivating retroviruses bearing a COL7A1 cDNA and cloned before the progeny of individual stem cells were characterised using a number of criteria. Clonal analysis revealed a great deal of heterogeneity among transduced stem cells in their capacity to produce functional type VII collagen (COLVII). Selected transduced stem cells transplanted onto immunodeficient mice regenerated a non-blistering epidermis for months and produced a functional COLVII. Safety was assessed by determining the sites of proviral integration, rearrangements and hit genes and by whole-genome sequencing. The progeny of the selected stem cells also had a diploid karyotype, was not tumorigenic and did not disseminate after long-term transplantation onto immunodeficient mice. In conclusion, a clonal strategy is a powerful and efficient means of by-passing the heterogeneity of a transduced stem cell population. It guarantees a safe and homogenous medicinal product, fulfilling the principle of precaution and the requirements of regulatory affairs. Furthermore, a clonal strategy makes it possible to envision exciting gene-editing technologies like zinc finger nucleases, TALENs and homologous recombination for next-generation gene therapy.

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Literature on medical dispatch is growing, focusing mainly on efficiency (under and overtriage) and dispatch-assisted CPR. But the issue of population catchment size, functional costs and rationalization is rarely addressed. If we can observe a trend toward a decreasing number of dispatch centres in many European countries, there is today no evidence on what is the right catchment size to reach the best balance between quality of services and costs.

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Despite decades of research, the exact pathogenic mechanisms underlying acute mountain sickness (AMS) are still poorly understood. This fact frustrates the search for novel pharmacological prophylaxis for AMS. The prevailing view is that AMS results from an insufficient physiological response to hypoxia and that prophylaxis should aim at stimulating the response. Starting off from the opposite hypothesis that AMS may be caused by an initial excessive response to hypoxia, we suggest that directly or indirectly blunting-specific parts of the response might provide promising research alternatives. This reasoning is based on the observations that (i) humans, once acclimatized, can climb Mt Everest experiencing arterial partial oxygen pressures (PaO2 ) as low as 25 mmHg without AMS symptoms; (ii) paradoxically, AMS usually develops at much higher PaO2 levels; and (iii) several biomarkers, suggesting initial activation of specific pathways at such PaO2 , are correlated with AMS. Apart from looking for substances that stimulate certain hypoxia triggered effects, such as the ventilatory response to hypoxia, we suggest to also investigate pharmacological means aiming at blunting certain other specific hypoxia-activated pathways, or stimulating their agonists, in the quest for better pharmacological prophylaxis for AMS.

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La reciente implantación y extensión de la red de alta velocidad ferroviaria en España está permitiendo relanzar un debate que en muchas ciudades no había sido resuelto de forma satisfactoria: la integración del ferrocarril en el medio urbano. En muchos casos, la llegada del nuevo tren se ha convertido en un instrumento urbanístico de primer orden, ya que conlleva una transformación de gran calado. En este artículo se realiza una lectura transversal, a través de las experiencias de diferentes ciudades españolas, para desarrollar una clasificación de las formas de integración de la alta velocidad ferroviaria y su impacto en la estructura urbana.

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Åbo 1757, Jacob Merckell

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Aboa 1755, Jacob Merckell

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Aboa 1755, Jacob Merckell