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

Fenómenos de retracción y comportamiento frente a la corrosión de materiales base cemento de bajo pH basados en OPC o CAC

Prior to using low-pH cementitious materials in underground repositories for high level waste, the characteristics determining their long-term durability must be analysed in depth. In this sense, different shrinkage tests have been made on mortar and concrete specimens using low-pH cement formulations based on ordinary portland cement (OPC) or calcium aluminate cement (CAC), with high mineral admixtures contents. They showed similar autogenous shrinkage than samples without mineral admixtures but higher drying shrinkage when materials based on OPC with high silica fume contents were considered. Besides, as the use of reinforced concrete could be required in underground repositories, the susceptibility of reinforcement to corrosion when using low-pH cementitious materials based on OPC was analyzed, considering carbon steel and galvanized steel. In the formers corrosion was detected due to the low pore solution pH but any problem was detected when galvanized reinforcement were used.Previo al empleo de materiales con cementos de bajo pH en almacenamientos geológicos profundos (AGP) de residuos radiactivos de alta actividad, características relacionadas con su durabilidad a largo plazo deben ser verificadas. Así, su estabilidad volumétrica se ha analizado en morteros y hormigones de bajo pH basados en OPC o CAC, con elevados contenidos de adiciones minerales. Estos presentaron retracciones autógenas similares a las medidas en materiales convencionales, pero retracciones por secado mayores en los basados en OPC y altos contenidos de humo de sílice. Dado que en zonas de los AGP podría emplearse hormigón armado, también se evaluó la susceptibilidad a la corrosión de aceros al carbono y aceros galvanizados en materiales de bajo pH basados en OPC. Se detectó un inicio temprano de corrosión en los primeros debido al bajo pH presente en el fluido de los poros de estos materiales, sin detectarse problemas al emplear aceros galvanizados

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

The nuclear and extended infrared emission of the Seyfert galaxy NGC 2992 and the interacting system Arp 245

We present subarcsecond resolution infrared (IR) imaging and mid-IR spectroscopic observations of the Seyfert 1.9 galaxy NGC 2992, obtained with the Gemini North Telescope and the Gran Telescopio CANARIAS (GTC). The N-band image reveals faint extended emission out to ~3 kpc, and the PAH features detected in the GTC/CanariCam 7.5-13 micron spectrum indicate that the bulk of this extended emission is dust heated by star formation. We also report arcsecond resolution MIR and far-IR imaging of the interacting system Arp 245, taken with the Spitzer Space Telescope and the Herschel Space Observatory. Using these data, we obtain nuclear fluxes using different methods and find that we can only recover the nuclear fluxes obtained from the subarcsecond data at 20-25 micron, where the AGN emission dominates. We fitted the nuclear IR spectral energy distribution of NGC 2992, including the GTC/CanariCam nuclear spectrum (~50 pc), with clumpy torus models. We then used the best-fitting torus model to decompose the Spitzer/IRS 5-30 spectrum (~630 pc) in AGN and starburst components, using different starburst templates. We find that, whereas at shorter mid-IR wavelengths the starburst component dominates (64% at 6 micron), the AGN component reaches 90% at 20 micron. We finally obtained dust masses, temperatures and star formation rates for the different components of the Arp 245 system and find similar values for NGC 2992 and NGC 2993. These measurements are within those reported for other interacting systems in the first stages of the interaction.Comment: 20 pages, 12 figures, accepted by MNRA