Economic evaluation of sunitinib versus pazopanib and best supportive care for the treatment of metastatic renal cell carcinoma in Chile: cost-effectiveness analysis and a mixed treatment comparison

© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group. Background: Sunitinib and Pazopanib are two metastatic renal cell carcinoma (MRCC) treatment alternatives, however the health system in Chile does not consider coverage for any. The cost-effectiveness versus relevant comparator was assessed to support evidence-based decision making. Methods: A four health states Markov model was built: first, second line treatments, BSC and death. Benefits were measured in QALYs, and efficacy estimates were obtained from an indirect treatment comparison. A 10-year time horizon and a 3% undifferentiated discount rate were considered. Deterministic and probabilistic sensitivity analyses were performed. Results: The costs of treating MRCC with Sunitinib were higher than Pazopanib and BSC. When comparing Sunitinib versus Pazopanib, the incremental benefit is small favoring Sunitinib (0.03 QALYs). The base case scenario shows an average ICER of PA versus BSC of US$62,327.11/QALY and of US$85,885/QALY for Sunitinib versus Pazopanib. The ICER was most sensitive to the OS relative to BSC, where evidence was associated to important bias. Conclusions: Sunitinib or Pazopanib can be considered cost-effective if a 3 GDP per-capita threshold is assumed. The decision between SU or PA is highly sensitive to the price of the drugs, rather than the outcomes. Therefore, the decision might be made based on cost-minimization exercise

Obtención de monoglicosidos de ageratina vacciniaefolia y determinación de su estructura tridimensional

La planta fue recolectada en el páramo Cruz Verde, ubicado sobre la vía que de Bogotá conduce a Choachí. Fue sometida a un proceso de extracción utilizando solventes de polaridad creciente y aislándolas por medio de cromatografía RP- 18 y Silica Gel, tanto de columna como de capa fina. La identificación de las sustancias fue realizada por medio del análisis de espectros de infrarojo, determinación del punto de fusión, actividad óptica, comportamiento ante reactivos químicos y el análisis de espectros unidimesionales de resonancia magnética nuclear tales como: H1, C13, DEPT 45, 90 y 135 y mediante el uso de los espectros bidimensionales COSY, HMQC y HMBC. Se encontró que las sustancias son diterpenos pertenecientes a la familia de los kauranos y se identificaron como (-)-17-(beta-glucopiranosiloxil)- kauran-19-oico-acid y (-)-16-(beta-glucopiranosiloxil)-16-ol-kauran-19-oicoacid Para la determinación de la configuración tridimensional se obtuvo monocristales utilizando el método de evaporación lenta desde una solución. Los párametros cristalográficos y las fases del factor de estructura fueron obtenidas directamente de las intensidades del patrón de difracción de rayos X (métodos directos). El refinamiento de los modelos se realizó utilizando el método de mínimos cuadrados

The History of Galveston's Concrete Ships

Selma is one of three World War I concrete shipwrecks in the Galveston area. While the other two are not identified, one of them is likely the Durham. This research explores how and why these ships ended their service here, and looks at the different methods used for the creation of early concrete ships and the differences in their performance. Selma, one of twelve Emergency Fleet Corporation ships, had a much different design than Durham, but both of the ships were out of use quickly after launch. Selma ran aground and damaged its bow; it was subsequently taken to Galveston for repairs that never occurred. Durham proved to be a very poor sailor, but remained afloat for many more years before becoming a fishing pier in Galveston. Both of these ships have histories of re-use that last beyond their abandonment. This research focuses on the history and construction of Selma and Durham. The text discusses the developments that lead to the development of these ships and how they fared after construction. Additionally, visual survey of how the condition of Selma has changed over time is included

Streptococcus pneumoniae TIGR4 flavodoxin: Structural and biophysical characterization of a novel drug target

Streptococcus pneumoniae (Sp) strain TIGR4 is a virulent, encapsulated serotype that causes bacteremia, otitis media, meningitis and pneumonia. Increased bacterial resistance and limited efficacy of the available vaccine to some serotypes complicate the treatment of diseases associated to this microorganism. Flavodoxins are bacterial proteins involved in several important metabolic pathways. The Sp flavodoxin (Spfld) gene was recently reported to be essential for the establishment of meningitis in a rat model, which makes SpFld a potential drug target. To facilitate future pharmacological studies, we have cloned and expressed SpFld in E. coli and we have performed an extensive structural and biochemical characterization of both the apo form and its active complex with the FMN cofactor. SpFld is a short-chain flavodoxin containing 146 residues. Unlike the well-characterized long-chain apoflavodoxins, the Sp apoprotein displays a simple two-state thermal unfolding equilibrium and binds FMN with moderate affinity. The X-ray structures of the apo and holo forms of SpFld differ at the FMN binding site, where substantial rearrangement of residues at the 91-100 loop occurs to permit cofactor binding. This work will set up the basis for future studies aiming at discovering new potential drugs to treat S. pneumoniae diseases through the inhibition of SpFld.We acknowledge financial support from BFU2010-16297 and BFU2010-19504 [Ministerio de Ciencia e Innovación Spain], BFU2013-47064-P, BIO2014-57314-REDT and CTQ2013-44367-C2-2-P [Ministerio de Economía y Competitividad, Spain], and DGA (Protein Targets B89). We also thank synchrotron radiation sources DLS (Oxford), and in particular beamline I04-1 (experiment number MX8035-3 and MX8035-11). The research leading to these results has also received funding from the FP7 (2007–2013) under BIOSTRUCTX-7687. A.R.C. was funded by a Banco Santander Central Hispano/Universidad de Zaragoza predoctoral fellowship. M. C-G was recipient of a predoctoral fellowship from the Government of Aragón.Peer Reviewe

Turbulencia empresarial en Colombia : sector de seguros

En el año 2010, la Facultad de Administración de la Universidad del Rosario puso en marcha un proyecto de investigación donde se exploraba el fenómeno de la turbulencia empresarial. En este momento han sido publicados más de 15 documentos donde se realiza la descripción de lo ocurrido en igual número de sectores. En este número se realiza un análisis del sector asegurador, actividad empresarial que contribuye de manera significativa a la economía del país. El trabajo ha sido realizado de manera conjunta por los profesores Natalia Malaver y Hugo Rivera de la asignatura Estrategia de empresa I, con estudiantes del pregrado de la Facultad, quienes se motivaron por encontrar respuestas a la forma como algunas empresas del sector enfrentan la turbulencia sectorial. La estructura del documento incluye una breve descripción del sector; luego un análisis de la turbulencia, y un estudio sectorial realizado aplicando la metodología del Análisis Estructural de Sectores Estratégicos (AESE) desarrollada por el grupo de investigación en perdurabilidad empresarial de la Facultad de Aministración de la Universidad del Rosario

Clay-induced DNA breaks as a path for genetic diversity, antibiotic resistance, and asbestos carcinogenesis

Natural clays and synthetic nanofibres can have a severe impact on human health. After several decades of research, the molecular mechanism of how asbestos induces cancer is not well understood. Different fibres, including asbestos, can penetrate cell membranes and introduce foreign DNA in bacterial and eukaryotic cells. Incubating Escherichia coli under friction forces with sepiolite, a clayey material, or with asbestos, causes double-strand DNA breaks. Antibiotics and clays are used together in animal husbandry, the mutagenic effect of these fibres could be a pathway to antibiotic resistance due to the friction provided by peristalsis of the gut from farm animals in addition to horizontal gene transfer. Moreover, we raise the possibility that the same mechanism could generate bacteria diversity in natural scenarios, playing a role in the evolution of species. Finally, we provide a new model on how asbestos may promote mutagenesis and cancer based on the observed mechanical genotoxicity

Size effects in the magnetic behaviour of TbAl_2 milled alloys

The study of the magnetic properties depending upon mechanical milling of the ferromagnetic polycrystalline TbAl_2 material is reported. The Rietveld analysis of the X-ray diffraction data reveals a decrease of the grain size down to 14 nm and -0.15 % of variation of the lattice parameter, after 300 hours of milling time. Irreversibility in the zero field cooled - field cooled (ZFC-FC) DC-susceptibility and clear peaks in the AC susceptibility between 5 and 300 K show that the long-range ferromagnetic structure is inhibited in favour of a disordered spin arrangement below 45 K. This glassy behaviour is also deduced from the variation of the irreversibility transition with the field (H^{2/3}) and frequency. The magnetization process of the bulk TbAl_2 is governed by domain wall thermal activation processes. By contrast, in the milled samples, cluster-glass properties arise as a result of cooperative interactions due to the substitutional disorder. The interactions are also influenced by the nanograin structure of the milled alloys, showing a variation of coercivity with the grain size, below the crossover between the multi- and single-domain behaviours.Comment: 23 pages, 11 figures, to appear in J. Phys.: Condens. Ma

Examination of the Feynman-Hibbs Approach in the Study of NeN_N-Coronene Clusters at Low Temperatures

Feynman-Hibbs (FH) effective potentials constitute an appealing approach for investigations of many-body systems at thermal equilibrium since they allow us to easily include quantum corrections within standard classical simulations. In this work we apply the FH formulation to the study of Ne$_N$-coronene clusters ($N=$ 1-4, 14) in the 2-14 K temperature range. Quadratic (FH2) and quartic (FH4) contributions to the effective potentials are built upon Ne-Ne and Ne-coronene analytical potentials. In particular, a new corrected expression for the FH4 effective potential is reported. FH2 and FH4 cluster energies and structures -obtained from energy optimization through a basin-hoping algorithm as well as classical Monte Carlo simulations- are reported and compared with reference path integral Monte Carlo calculations. For temperatures $T> 4$ K, both FH2 and FH4 potentials are able to correct the purely classical calculations in a consistent way. However, the FH approach fails at lower temperatures, especially the quartic correction. It is thus crucial to assess the range of applicability of this formulation and, in particular, to apply the FH4 potentials with great caution. A simple model of $N$ isotropic harmonic oscillators allows us to propose a means of estimating the cut-off temperature for the validity of the method, which is found to increase with the number of atoms adsorbed on the coronene molecule

Quantum Zeno and anti-Zeno effects in surface diffusion of interacting adsorbates

Surface diffusion of interacting adsorbates is here analyzed within the context of two fundamental phenomena of quantum dynamics, namely the quantum Zeno effect and the anti-Zeno effect. The physical implications of these effects are introduced here in a rather simple and general manner within the framework of non-selective measurements and for two (surface) temperature regimes: high and very low (including zero temperature). The quantum intermediate scattering function describing the adsorbate diffusion process is then evaluated for flat surfaces, since it is fully analytical in this case. Finally, a generalization to corrugated surfaces is also discussed. In this regard, it is found that, considering a Markovian framework and high surface temperatures, the anti-Zeno effect has already been observed, though not recognized as such.Comment: 17 pages, 1 figur

Proxima Centauri b is not a transiting exoplanet

We report Spitzer Space Telescope observations during predicted transits of the exoplanet Proxima Centauri b. As the nearest terrestrial habitable-zone planet we will ever discover, any potential transit of Proxima b would place strong constraints on its radius, bulk density, and atmosphere. Subsequent transmission spectroscopy and secondary-eclipse measurements could then probe the atmospheric chemistry, physical processes, and orbit, including a search for biosignatures. However, our photometric results rule out planetary transits at the 200~ppm level at 4.5$~{\mu}m$, yielding a 3$\sigma$ upper radius limit of 0.4~R_\rm{\oplus} (Earth radii). Previous claims of possible transits from optical ground- and space-based photometry were likely correlated noise in the data from Proxima Centauri's frequent flaring. Follow-up observations should focus on planetary radio emission, phase curves, and direct imaging. Our study indicates dramatically reduced stellar activity at near-to-mid infrared wavelengths, compared to the optical. Proxima b is an ideal target for space-based infrared telescopes, if their instruments can be configured to handle Proxima's brightness.Comment: 8 pages, 3 figures, 2 tables, accepted for publication in MNRA