Guía para la implementación de la norma ISO 9001:2008 para establecimientos farmacéuticos a partir del instrumento de verificación contemplado en la Resolución 0444 del 2008

The purpose of this guide is to show a basic model that allows design and implement a system of quality management ISO 9001:2008 with the Good Manufacturing Practices (BPE) existing in the Colombian pharmaceutical industry. This project which has been called "Guidelines for the implementation of ISO 9001:2008 for Pharmaceutical Establishments from the verification instrument referred to in Resolution 0444 of 2008", is aimed especially at those who provide pharmaceutical services under the name Mixtures of Central parenteral, focusing on certification under ISO 9001 for the attention of the users. Pharmaceutical establishments face daily challenges which bring into play complex survival of health systems. To do this, management systems are required agile and modern, tailored to meet needs not only of customers, patients and / or users, also from the regulatory authorities and other stakeholders. The guide was made from the activities in pharmaceutical services covered by the resolution 0444 of 2008 published by the ministry of social protection. Are specified in this harmonization and integration elements that provide insight into the similarities between the two standards and provide information on how to implement the requirements of ISO are not covered by Colombian law, thus implementing a quality management compatible and consistent with existing regulations.El objetivo de la presente guía es mostrar un modelo básico que permita diseñar e implementar un sistema de gestión de la calidad según la norma ISO 9001:2008 con las Buenas Prácticas de Elaboración (BPE) existentes en la industria farmacéutica colombiana. Este proyecto el cual se ha denominado: “Guía para la implementación de la Norma ISO 9001: 2008 para Establecimientos Farmacéuticos a partir del Instrumento de verificación contemplado en la Resolución 0444 del 2008”; está orientada especialmente a quienes prestan sus servicios farmacéuticos bajo la denominación de Centrales de Mezclas Parenterales, enfocando la certificación bajo la norma ISO 9001 en la atención a los usuarios. Los establecimientos farmacéuticos enfrentan diariamente retos complejos que ponen en juego la supervivencia de los sistemas de salud. Para ello, son necesarios sistemas de gestión ágiles y modernos, adaptados a resolver necesidades no solo de los clientes, pacientes y/o usuarios, también de las autoridades regulatorias y demás partes interesadas. La guía se realizó a partir de las actividades desarrolladas en los servicios farmacéuticos que trata la resolución 0444 de 2008 publicada por el ministerio de la protección social. En la presente se concretan elementos de armonización e integración que permiten conocer las similitudes entre ambas normas y brindar información de cómo se puede aplicar los requisitos de la norma ISO que no se encuentran contemplados en la legislación Colombiana, implementando así un sistema de gestión de calidad compatible y coherente con la reglamentación vigente

Régimen general de los beneficiarios en el contrato de seguro

Especialista en Derecho de SegurosEspecializació

Estimationof the energy saving potentials in foundry industries based on iso 50001

This paper presents the application of tools to develop a procedure to estimate the energy saving potentials in a small foundry company in Colombia, based on the ISO 50001 standard. This work was carried within the framework of a national industrial project, funded by UNIDO, aimed at the small and medium industrial sector companies (SMEs) of Valle del Cauca, to establish the requirements that are needed to implement an energy management system. With the aim of increasing the energy efficiency of the processes, the energy planning process proposed by ISO 50001 is carried out, whose lead to the establishment of concrete and attainable goals, as well as to the proposal of various improvement plans regarding savings and efficient use of energy. As a result, the savings potentials for the different production levels were estimated, which represents a saving of 15984.25 kWh, which corresponds to 8.7% of the total energy consumed in the 10 months analyzed, and a value of 1486 US

Electronic Conductance and Thermopower of Cross-Conjugated and Skipped-Conjugated Molecules in Single-Molecule Junctions

We report a combined experimental and theoretical study of a series of thiomethyl (SMe) anchored cross-conjugated molecules featuring an acyclic central bridging ketone and their analogous skipped-conjugated alcohol derivatives. Studies of these molecules in a gold|single-molecule|gold junction using scanning tunneling microscopy-break junction techniques reveal a similar conductance (G) value for both the cross-conjugated molecules and their skipped-conjugated partners. Theoretical studies based on density functional theory of the molecules in their optimum geometries in the junction reveal the reason for this similarity in conductance, as the predicted conductance for the alcohol series of compounds varies more with the tilt angle. Thermopower measurements reveal a higher Seebeck coefficient (S) for the cross-conjugated ketone molecules relative to the alcohol derivatives, with a particularly high S for the biphenyl derivative 3a (−15.6 μV/K), an increase of threefold compared to its alcohol analog. The predicted behavior of the quantum interference (QI) in this series of cross-conjugated molecules is found to be constructive, though the appearance of a destructive QI feature for 3a is due to the degeneracy of the HOMO orbital and may explain the enhancement of the value of S for this molecule

Quantum interference dependence on molecular configurations for cross-conjugated systems in single-molecule junctions

We report a combined experimental and computational study of seven cross-conjugated enediyne derivatives functionalised with a pendant group (diphenyl, 9-fluorenyl, 9-thioxanthene or cyclohexyl) at the central alkene site, and with thiomethyl (SMe) or thioacetate, as protected thiol, (SAc) groups as anchors. Measurements of the conductance (G) and Seebeck coefficient (S) of gold|single-molecule|gold junctions were obtained using a modified scanning tunnelling microscope-break junction (STM-BJ) technique. It is shown that most of the molecules give multiple conductance plateaus ascribed to different molecular configurations inside the junction. The higher conductance plateaus are consistent with the aryl pendant units interacting with one of the gold electrodes, thereby circumventing transmission of electrons through the enediyne system; the lower conductance plateaus are consistent with anchoring of both of the terminal SMe or S units to the electrodes. Most of the compounds show a positive value of S in the range 3.7–12.7 μV K−1 indicating electronic transport through the HOMO, while one of them presents a negative value of S (−6.2 μV K−1) indicating a predominance of the LUMO in the electronic transport. Theoretical calculations using density functional theory show a destructive quantum interference (DQI) feature in the gap between the highest occupied and lowest unoccupied molecular orbitals (the HOMO–LUMO gap) for the lower conductance plateaus, supporting the trends observed in the experimental data

La formación continua y los jóvenes empresarios

El libro presenta los resultados de un estudio a nivel andaluz sobre las necesidades de formación de los jóvenes empresarios de la comunidad Andaluza. El objetivo general de la acción llevada a cabo consiste en realizar un diagnóstico de las necesidades de formación continua entre algunas líneas de actividad del sector empresarial andaluz (servicios empresariales, publicidad, empresas de actividades deportivas y comercio minorista), con una especial atención a las empresas dirigidas y gestionadas por jóvenes empresarios. El conocimiento de las necesidades de formación continua trata de poner de manifiesto los déficits objetivamente existentes entre la realidad de la actividad laboral y lo que sería deseable, déficits que son salvables mediante acciones de formación. Entre los objetivos específicos de la acción podemos destacar los siguientes: 1. Detección de necesidades de formación continua que puedan ser satisfechas, así como un análisis de las características requeridas por los potenciales destinatarios atendiendo a los diferentes segmentos de población objetivo. 2. Agrupamiento de información relacionada con competencias necesarias para desempeñar los puestos de trabajo englobados en el marco de las empresas objeto de la muestra. 3. Un estudio de futuros cambios significativos (innovaciones tecnológicas y/u organizativas, lanzamiento de actividades, etc.) que pudieran justificar unas exigencias especiales de formación para el personal de las empresas encuestadas. 3. Redacción de un informe sobre necesidades de formación en el que se manifiesten, de una parte, los contenidos u objetivos de la formación, así como sus demandantes atendiendo a la orientación estratégica y cultural de éstos; y de otra, la distribución numérica de las necesidades, lo que nos permitirá aproximarnos mejor a los centros de demanda. 4. Establecimiento de prioridades en el orden de ejecución de los programas de formación continua.FUNDACIÓN PARA LA FORMACIÓN CONTINUA EN LA EMPRESA (FORCEM). ASOCIACIÓN DE JÓVENES EMPRESARIOS DE ANDALUCÍA (AJE

Long-lived charged states of single porphyrin-tape junctions under ambient conditions

The ability to control the charge state of individual molecules wired in two-terminal single-molecule junctions is a key challenge in molecular electronics, particularly in relation to the development of molecular memory and other computational componentry. Here we demonstrate that single porphyrin molecular junctions can be reversibly charged and discharged at elevated biases under ambient conditions due to the presence of a localised molecular eigenstate close to the Fermi edge of the electrodes. In particular, we can observe long-lived charge-states with lifetimes upwards of 1–10 seconds after returning to low bias and large changes in conductance, in excess of 100-fold at low bias. Our theoretical analysis finds charge-state lifetimes within the same time range as the experiments. The ambient operation demonstrates that special conditions such as low temperatures or ultra-high vacuum are not essential to observe hysteresis and stable charged molecular junctions

Molecular Structure-(Thermo)electric Property Relationships in Single-Molecule Junctions and Comparisons with Single- and Multiple-Parameter Models

The most probable single-molecule conductance of each member of a series of 12 conjugated molecular wires, 6 of which contain either a ruthenium or platinum center centrally placed within the backbone, has been determined. The measurement of a small, positive Seebeck coefficient has established that transmission through these molecules takes place by tunneling through the tail of the HOMO resonance near the middle of the HOMO–LUMO gap in each case. Despite the general similarities in the molecular lengths and frontier-orbital compositions, experimental and computationally determined trends in molecular conductance values across this series cannot be satisfactorily explained in terms of commonly discussed “single-parameter” models of junction conductance. Rather, the trends in molecular conductance are better rationalized from consideration of the complete molecular junction, with conductance values well described by transport calculations carried out at the DFT level of theory, on the basis of the Landauer–Büttiker model

EVC-EVC2 complex stability and ciliary targeting are regulated by modification with ubiquitin and SUMO

Ellis van Creveld syndrome and Weyers acrofacial dysostosis are two rare genetic diseases affecting skeletal development. They are both ciliopathies, as they are due to malfunction of primary cilia, microtubule-based plasma membrane protrusions that function as cellular antennae and are required for Hedgehog signaling, a key pathway during skeletal morphogenesis. These ciliopathies are caused by mutations affecting the EVC-EVC2 complex, a transmembrane protein heterodimer that regulates Hedgehog signaling from inside primary cilia. Despite the importance of this complex, the mechanisms underlying its stability, targeting and function are poorly understood. To address this, we characterized the endogenous EVC protein interactome in control and Evc-null cells. This proteomic screen confirmed EVC’s main known interactors (EVC2, IQCE, EFCAB7), while revealing new ones, including USP7, a deubiquitinating enzyme involved in Hedgehog signaling. We therefore looked at EVC-EVC2 complex ubiquitination. Such ubiquitination exists but is independent of USP7 (and of USP48, also involved in Hh signaling). We did find, however, that monoubiquitination of EVC-EVC2 cytosolic tails greatly reduces their protein levels. On the other hand, modification of EVC-EVC2 cytosolic tails with the small ubiquitin-related modifier SUMO3 has a different effect, enhancing complex accumulation at the EvC zone, immediately distal to the ciliary transition zone, possibly via increased binding to the EFCAB7-IQCE complex. Lastly, we find that EvC zone targeting of EVC-EVC2 depends on two separate EFCAB7-binding motifs within EVC2’s Weyers-deleted peptide. Only one of these motifs had been characterized previously, so we have mapped the second herein. Altogether, our data shed light on EVC-EVC2 complex regulatory mechanisms, with implications for ciliopathies

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality