The relationship of drug reimbursement with the price and the quality of pharmaceutical innovations

This paper studies the strategic interaction between pharmaceutical firms' pricing decisions and government agencies' reimbursement decisions which discriminate between patients by giving reimbursement rights to patients for whom the drug is most effective. We show that if the reimbursement decision preceeds the pricing decision, the agency only reimburses some patients if the private and public health benefits from the new drug diverge. That is, when (i) there are large externalities of consuming the drug and (ii) the difference in costs between the new drug and the alternative treatment is large. Alternatively, if the firm can commit to a price in advance of the reimbursement decision, we identify a strategic effect which implies that by committing to a high price ex ante, the firm can force a listing outcome and make the agency more willing to reimburse than in the absence of commitment

Cell adhesion on ti surface with controlled roughness

In this report, the in situ interaction between Saos-2 osteoblast cells and a smooth Ti surface was examined over time. The adhesion kinetics and mechanisms of cellular proliferation were monitored by quartz crystal microbalance (QCM) and electrochemical impedance spectroscopy (EIS). The rate of Saos-2 attachment on Ti surfaces, obtained from the measurements performed with the QCM, is a first-order reaction, with k=2.103 min1. The impedance measurements indicate that in the absence of cells, the Ti resistance diminishes over time (7 days), due to the presence of amino acids and proteins from the culture medium that have been a dsorbed, while in the presence of osteoblasts, this decrease is much greater because of the compounds generated by the cells that accelerate the dissolution of TiAdhesión de osteoblastos sobre una superficie de Ti de rugosidad controlada. En este trabajo, se ha estudiado la interacción in situ entre células osteoblásticas Saos-2 y una superficie de Ti de rugosidad controlada a lo largo del tiempo. El estudio de la cinética y los mecanismos de proliferación celular de adhesión se ha realizado a través de la microbalanza de cristal de cuarzo (QCM) y espectroscopía de impedancia electroquímica (EIS). La velocidad de adhesión de los osteoblastos sobre la superficie de Ti obtenida a través de medidas con la QCM, sigue una reacción de primer orden, con k=2×10−3 min−1. Los ensayos de impedancia indican que, en ausencia de las células, la resistencia del Ti disminuye con el tiempo (7 días), debido a la presencia de aminoácidosy proteínas del medio de cultivo que se han adsorbido, mientras que en presencia de células, esta disminución es mucho mayor debido a los productos metabólicos generados por las células que aceleran la disolución del TiThe authors thank the financial support under projects MAT 2008-06719-C03-01, CTQ2008-05775/ BQU and by the Comunidad Autónoma de Madrid (CAM) through AVANSENS S2009/PPQ-164

Complicaciones a corto plazo de la artroplastia total primaria de cadera

Objetivos: Se pretende analizar las principales complicaciones a corto plazo (seis semanas) tras la Artroplastia total primaria de cadera. ;aterial y métodos: Se revisaron todos los pacientes a los que se realizó artroplastia total de cadera durante el año 2003. Las variables estudiadas fueron el índice de luxaciones, sangrado, infección, fracturas periprotésicas, complicaciones vásculo-nerviosas y mortalidad. Resultados: Obtuvimos una tasa del 4,4% de luxaciones; 1,7% de trombosis venosa profunda con un 0,87% de embolismo pulmonar, 1,7% de infecciones superficiales sin casos de infección profunda. El 14,9% de los casos necesitaron una transfusión postquirúrgica. Intraoperatoriamente observamos apertura del cálcar en el 3,5%, y fracturas periprotésicas postoperatorias en el 0,87%. No registramos complicaciones neurológicas ni mortalidad en estas primeras seis semanas del estudio. Conclusiones: La complicación más frecuente es la luxación, fundamentalmente en los casos secundarios a fractura. La trombosis venosa profunda, a èsar de la profilaxis, continúa siendo una complicación frecuente.Objectives: Our purpose was to analyze the main early complications (six weeks) after primary total hip arthroplasty. Materials and Methods: All patients who had undergone primary total hip replacement during 2003 were reviewed. The studied outcomes were the rates of dislocation, blood loss, infection, periprosthetic fractures, neural and vascular complications, and mortality. Results: Our rates were 4,4% for hip dislocation, 1,7% for deep vein thrombosis with 0,87% for pulmonary embolism, 1,7% for wound infection without cases of deep infection. 14,9% of the patients needed postoperative transfusion. We reported 3,5% fractures of the calcar during surgery and 0,87% of postoperative periprosthetic fractures. We didn ́t reported any neural complications or mortality within six weeks postoperatively. Conclusions: The most frequent complication is dislocation, mainly in cases whose underlying diagnose was hip fracture. Although prophylaxis is done, deep vein thrombosis goes on being a frequent complication

Continuous spectra in high-harmonic generation driven by multicycle laser pulses

We present observations of the emission of XUV continua in the 20-37 eV region by high harmonic generation (HHG) with $4$-$7\ \mathrm{fs}$ pulses focused onto a Kr gas jet. The underlying mechanism relies on coherent control of the relative delays and phases between individually generated attosecond pulse, achievable by adjusting the chirp of the driving pulses and the interaction geometry. Under adequate negative chirp and phase matching conditions, the resulting interpulse interference yields a continuum XUV spectrum, which is due to both microscopic and macroscopic (propagation) contributions. This technique opens the route for modifying the phase of individual attosecond pulses and for the coherent synthesis of XUV continua from multicycle driving laser pulses without the need of an isolated attosecond burst.Comment: 14 pages, 5 figures. Submitted to Physical Review

Diseño eficiente de elementos constructivos: fachadas.

Se presentan la metodología y algunos resultados para el análisis de elementos constructivos de fachada de edificios de viviendas en España desde una perspectiva de ciclo de vida, teniendo en cuenta el impacto ambiental de los materiales que componen dicha fachada, y sus prestaciones en la fase de uso de las viviendas. Para ello se ha tomado un modelo de vivienda, y se han estudiado diferentes escenarios para la construcción de la fachada. Los resultados obtenidos proporcionan datos de referencia del comportamiento de estos sistemas en España, y permiten detectar las mejores estrategias para reducir el consumo energético en viviendas, en una amplia variedad de situaciones posibles, que se dan tanto en fachadas de nueva construcción como en la rehabilitación de fachadas existentes. Las categorías de impacto estudiadas son: consumo de combustibles fósiles y cambio climático y las estrategias de diseño están vinculadas a las zonas climáticas, la orientación, renovación del aire interior, materiales y composición de fachada. Tanto el enfoque como los resultados obtenidos suponen una aportación para la valoración ambiental de las estrategias de diseño en una fase inicial de proyecto

Influence of inflammation in the process of T lymphocyte differentiation: Proliferative, metabolic, and oxidative changes

T lymphocytes, from their first encounter with their specific antigen as naïve cell until the last stages of their differentiation, in a replicative state of senescence, go through a series of phases. In several of these stages, T lymphocytes are subjected to exponential growth in successive encounters with the same antigen. This entire process occurs throughout the life of a human individual and, earlier, in patients with chronic infections/pathologies through inflammatory mediators, first acutely and later in a chronic form. This process plays a fundamental role in amplifying the activating signals on T lymphocytes and directing their clonal proliferation. The mechanisms that control cell growth are high levels of telomerase activity and maintenance of telomeric length that are far superior to other cell types, as well as metabolic adaptation and redox control. Large numbers of highly differentiated memory cells are accumulated in the immunological niches where they will contribute in a significant way to increase the levels of inflammatory mediators that will perpetuate the new state at the systemic level. These levels of inflammation greatly influence the process of T lymphocyte differentiation from naïve T lymphocyte, even before, until the arrival of exhaustion or cell death. The changes observed during lymphocyte differentiation are correlated with changes in cellular metabolism and these in turn are influenced by the inflammatory state of the environment where the cell is located. Reactive oxygen species (ROS) exert a dual action in the population of T lymphocytes. Exposure to high levels of ROS decreases the capacity of activation and T lymphocyte proliferation; however, intermediate levels of oxidation are necessary for the lymphocyte activation, differentiation, and effector functions. In conclusion, we can affirm that the inflammatory levels in the environment greatly influence the differentiation and activity of T lymphocyte populations. However, little is known about the mechanisms involved in these processes. The elucidation of these mechanisms would be of great help in the advance of improvements in pathologies with a large inflammatory base such as rheumatoid arthritis, intestinal inflammatory diseases, several infectious diseases and even, cancerous processes