Prescripción inducida en atención primaria de la Comarca Bilbao

ObjetivosPrincipales: conocer la proporción de prescripción inducida (PI) en Comarca Bilbao y su procedencia, la proporción de gasto correspondiente a la PI, la proporción de PI en los principales grupos terapéuticos, la actitud del médico de atención primaria ante la prescripción solicitada y su influencia en el gasto, la proporción de desacuerdo con dicha prescripción y los motivos de desacuerdo, y la proporción con informe del especialista. Secundarios: conocer la proporción de PI en los demás grupos terapéuticos, en fármacos VINE, EFG y en los de nula o baja mejora terapéutica.Diseño.Estudio transversal, descriptivoEmplazamientoAtención primariaParticipantesFármacos financiables prescritos por y/o solicitados a los médicos de familia de EAP.Resultados principalesSe estudiaron 7.922 fármacos. Tipo de prescripción: PI, 48,3% (IC del 95%, 47,2–49,4); del médico de atención primaria (PRO), 50,6% (IC del 95%, 49,5–51,7); desconocida, 1,1% (IC del 95%, 0,9–1,3). Procedencia principal: especialista público (72,2%), especialista privado (16,6%). Un 62,5% del gasto correspondió a la PI. En el grupo terapéutico más prescrito, sistema nervioso central (24,2%), PI, 39,8%; PRO, 58,9%; en aparato cardiovascular (19,1%), PI, 56,2%, PRO, 43,1%. Se prescribió el fármaco solicitado en un 98,4% de los casos, se cambio en el 1,2% y se suprimió en un 0,4%. Proporción de desacuerdo, 11%; motivos de desacuerdo, no hay necesidad de tratar (23,9%), grupo terapéutico (34,4%), principio activo (13,2%), marca comercial (28,5%). Hubo informe de especialista en un 62,4% de los casos.ConclusionesSe detecta una proporción considerable de prescripción no atribuible a atención primaria y una proporción importante de fármacos que el médico de primaria prescribe sin estar de acuerdo. Sería necesario un sistema que permitiera separar el gasto por niveles, así como mejorar la comunicación entre éstos.ObjectivesMain objetives: to know the proportion of induced prescription (IP) in Area Bilbao and its source, the proportion of cost IP accounts for, the proportion of IP in the main therapeutic groups, the attitude of GP when requested for prescription and its influence on cost, the proportion of disagreement with requested prescription, the reasons for disagreement, and the proportion with letter from specialist. Secondary objectives: to know the proportion of IP in the remaining therapeutic groups, in drugs of low clinical value, in generic drugs and in new drugs with low or no therapeutic improvement.DesignA descriptive cross-sectional study.SettingPrimary health care.ParticipantsDrugs prescribable under National Health Service prescribed by and/or requested to GPs.Main results7.922 drugs were analysed. Type of prescription: IP, 48.3% (95% CI, 47.2–49.4); GP prescription (GPP), 50.6% (95% CI, 49.5–51.7); unknown source, 1,1% (95% CI, 0.9–1.3). Main source, public specialist (72.2%), private specialist (16.6%). IP accounted for 62.5% of cost. In the most prescribed therapeutic group, central nervous system (24.2%), IP, 39.8%; GPP, 58.9%; in cardiovascular system (19.1%), IP, 56.2%; GPP, 43.1%. 98.4% of requested prescription was actually prescribed, 1.2% was changed and 0.4%, suppressed. Proportion of disagreement, 11%; reasons for disagreement, no need for medical treatment (23.9%), therapeutic group (34.4%), active ingredient (13.2%), brand name (28.5%). There was a 62.4% with letter from specialist.ConclusionsPrimary care is not accountable for a substantial proportion of prescription. GP prescribes a considerable proportion of drugs without agreement. It would be necessary a system that allows to separate the cost by care levels and also improve their communication

Lower Rydberg series of methane : A combined coupled cluster linear response and molecular quantum defect orbital calculation

Vertical excitation energies as well as related absolute photoabsorption oscillator strength data are very scarce in the literature for methane. In this study, we have characterized the three existing series of low-lying Rydberg states of CH4 by computing coupled cluster linear response (CCLR) vertical excitation energies together with oscillator strengths in the molecular-adapted quantum defect orbital formalism from a distorted Cs geometry selected on the basis of outer valence green function calculations. The present work provides a wide range of data of excitation energies and absolute oscillator strengths which correspond to the Rydberg series converging to the three lower ionization potential values of the distorted methane molecule, in energy regions for which experimentally measured data appear to be [email protected] [email protected] [email protected]

Pranlukast Antagonizes CD49f and Reduces Sternness in Triple-Negative Breast Cancer Cells

Introduction: Cancer stem cells (CSCs) drive the initiation, maintenance, and therapy response of breast tumors. CD49f is expressed in breast CSCs and functions in the maintenance of stemness. Thus, blockade of CD49f is a potential therapeutic approach for targeting breast CSCs. In the present study, we aimed to repurpose drugs as CD49f antagonists. Materials and Methods: We performed consensus molecular docking using a subdomain of CD49f that is critical for heterodimerization and a collection of pharmochemicals clini-cally tested. Molecular dynamics simulations were employed to further characterize drug-target binding. Using MDA-MB-231 cells, we evaluated the effects of potential CD49f antagonists on 1) cell adhesion to laminin; 2) mammosphere formation; and 3) cell viability. We analyzed the effects of the drug with better CSC-selectivity on the activation of CD49f-downstream signaling by Western blot (WB) and co-immunoprecipitation. Expressions of the stem cell markers CD44 and SOX2 were analyzed by flow cytometry and WB, respectively. Transactivation of SOX2 promoter was evaluated by luciferase reporter assays. Changes in the number of CSCs were assessed by limiting-dilution xenotransplantation. Results: Pranlukast, a drug used to treat asthma, bound to CD49f in silico and inhibited the adhesion of CD49f+ MDA-MB-231 cells to laminin, indicating that it antagonizes CD49f-containing integrins. Molecular dynamics analysis showed that pranlukast binding induces con-formational changes in CD49f that affect its interaction with β1-integrin subunit and constrained the conformational dynamics of the heterodimer. Pranlukast decreased the clonogenicity of breast cancer cells on mammosphere formation assay but had no impact on the viability of bulk tumor cells. Brief exposure of MDA-MB-231 cells to pranlukast altered CD49f-dependent signaling, reducing focal adhesion kinase (FAK) and phosphatidylinositol 3-kinase (PI3K) activation. Further, pranlukast-treated cells showed decreased CD44 and SOX2 expression, SOX2 promoter transacti-vation, and in vivo tumorigenicity, supporting that this drug reduces the frequency of CSC. Conclusion: Our results support the function of pranlukast as a CD49f antagonist that reduces the CSC population in triple-negative breast cancer cells. The pharmacokinetics and toxicology of this drug have already been established, rendering a potential adjuvant therapy for breast cancer patients

Observation of the Crab Nebula with the HAWC Gamma-Ray Observatory

The Crab Nebula is the brightest TeV gamma-ray source in the sky and has been used for the past 25 years as a reference source in TeV astronomy, for calibration and verification of new TeV instruments. The High Altitude Water Cherenkov Observatory (HAWC), completed in early 2015, has been used to observe the Crab Nebula at high significance across nearly the full spectrum of energies to which HAWC is sensitive. HAWC is unique for its wide field-of-view, nearly 2 sr at any instant, and its high-energy reach, up to 100 TeV. HAWC's sensitivity improves with the gamma-ray energy. Above $\sim$1 TeV the sensitivity is driven by the best background rejection and angular resolution ever achieved for a wide-field ground array. We present a time-integrated analysis of the Crab using 507 live days of HAWC data from 2014 November to 2016 June. The spectrum of the Crab is fit to a function of the form $\phi(E) = \phi_0 (E/E_{0})^{-\alpha -\beta\cdot{\rm{ln}}(E/E_{0})}$. The data is well-fit with values of $\alpha=2.63\pm0.03$, $\beta=0.15\pm0.03$, and log$_{10}(\phi_0~{\rm{cm}^2}~{\rm{s}}~{\rm{TeV}})=-12.60\pm0.02$ when $E_{0}$ is fixed at 7 TeV and the fit applies between 1 and 37 TeV. Study of the systematic errors in this HAWC measurement is discussed and estimated to be $\pm$50\% in the photon flux between 1 and 37 TeV. Confirmation of the Crab flux serves to establish the HAWC instrument's sensitivity for surveys of the sky. The HAWC survey will exceed sensitivity of current-generation observatories and open a new view of 2/3 of the sky above 10 TeV.Comment: Submitted 2017/01/06 to the Astrophysical Journa

The 2HWC HAWC Observatory Gamma Ray Catalog

We present the first catalog of TeV gamma-ray sources realized with the recently completed High Altitude Water Cherenkov Observatory (HAWC). It is the most sensitive wide field-of-view TeV telescope currently in operation, with a 1-year survey sensitivity of ~5-10% of the flux of the Crab Nebula. With an instantaneous field of view >1.5 sr and >90% duty cycle, it continuously surveys and monitors the sky for gamma ray energies between hundreds GeV and tens of TeV. HAWC is located in Mexico at a latitude of 19 degree North and was completed in March 2015. Here, we present the 2HWC catalog, which is the result of the first source search realized with the complete HAWC detector. Realized with 507 days of data and represents the most sensitive TeV survey to date for such a large fraction of the sky. A total of 39 sources were detected, with an expected contamination of 0.5 due to background fluctuation. Out of these sources, 16 are more than one degree away from any previously reported TeV source. The source list, including the position measurement, spectrum measurement, and uncertainties, is reported. Seven of the detected sources may be associated with pulsar wind nebulae, two with supernova remnants, two with blazars, and the remaining 23 have no firm identification yet.Comment: Submitted 2017/02/09 to the Astrophysical Journa

Evidence of paleoecological changes and Mousterian occupations at the Galeria de las Estatuas site, Sierra de Atapuerca, northern Iberian plateau, Spain

Here we present a new site in the Sierra de Atapuerca (Burgos, Spain): Galeria de las Estatuas (GE), which provides new information about Mousterian occupations in the Iberian Plateau. The GE was an ancient entrance to the cave system, which is currently closed and sealed by a stalagmitic crust, below which a detritic sedimentary sequence of more than 2 m is found. This has been divided into five litostratigraphic units with a rich assemblage of faunal and lithic remains of clear Mousterian affinity. Radiocarbon dates provide minimum ages and suggest occupations older than 45 C-14 ka BP. The palynological analysis detected a landscape change to increased tree coverage, which suggests that the sequence recorded a warming episode. The macromammal assemblage is composed of both ungulates (mainly red deer and equids) and carnivores. Taphonomic analysis reveals both anthropic, and to a lesser extent, carnivore activities. The GE was occupied by Neanderthals and also sporadically by carnivores. This new site broadens the information available regarding different human occupations at the Sierra de Atapuerca, which emphasizes the importance of this site-complex for understanding human evolution in Western Europe

Daily monitoring of TeV gamma-ray emission from Mrk 421, Mrk 501, and the Crab Nebula with HAWC

We present results from daily monitoring of gamma rays in the energy range $\sim0.5$ to $\sim100$ TeV with the first 17 months of data from the High Altitude Water Cherenkov (HAWC) Observatory. Its wide field of view of 2 steradians and duty cycle of $>95$% are unique features compared to other TeV observatories that allow us to observe every source that transits over HAWC for up to $\sim6$ hours each sidereal day. This regular sampling yields unprecedented light curves from unbiased measurements that are independent of seasons or weather conditions. For the Crab Nebula as a reference source we find no variability in the TeV band. Our main focus is the study of the TeV blazars Markarian (Mrk) 421 and Mrk 501. A spectral fit for Mrk 421 yields a power law index $\Gamma=2.21 \pm0.14_{\mathrm{stat}}\pm0.20_{\mathrm{sys}}$ and an exponential cut-off $E_0=5.4 \pm 1.1_{\mathrm{stat}}\pm 1.0_{\mathrm{sys}}$ TeV. For Mrk 501, we find an index $\Gamma=1.60\pm 0.30_{\mathrm{stat}} \pm 0.20_{\mathrm{sys}}$ and exponential cut-off $E_0=5.7\pm 1.6_{\mathrm{stat}} \pm 1.0_{\mathrm{sys}}$ TeV. The light curves for both sources show clear variability and a Bayesian analysis is applied to identify changes between flux states. The highest per-transit fluxes observed from Mrk 421 exceed the Crab Nebula flux by a factor of approximately five. For Mrk 501, several transits show fluxes in excess of three times the Crab Nebula flux. In a comparison to lower energy gamma-ray and X-ray monitoring data with comparable sampling we cannot identify clear counterparts for the most significant flaring features observed by HAWC.Comment: 18 pages, 10 figures, accepted for publication in The Astrophysical Journa