999 resultados para Pinto, Jeffrey K


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Kirjallisuusarvostelu

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Oropouche virus (OROV) is a member of the Orthobunyavirus genus in the Bunyaviridae family and a prominent cause of insect-transmitted viral disease in Central and South America. Despite its clinical relevance, little is known about OROV pathogenesis. To define the host defense pathways that control OROV infection and disease, we evaluated OROV pathogenesis and immune responses in primary cells and mice that were deficient in the RIG-I-like receptor signaling pathway (MDA5, RIG-I, or MAVS), downstream regulatory transcription factors (IRF-3 or IRF-7), IFN-β, or the receptor for type I IFN signaling (IFNAR). OROV replicated to higher levels in primary fibroblasts and dendritic cells lacking MAVS signaling, the transcription factors IRF-3 and IRF-7, or IFNAR. In mice, deletion of IFNAR, MAVS, or IRF-3 and IRF-7 resulted in uncontrolled OROV replication, hypercytokinemia, extensive liver damage, and death whereas wild-type (WT) congenic animals failed to develop disease. Unexpectedly, mice with a selective deletion of IFNAR on myeloid cells (CD11c Cre(+) Ifnar(f/f) or LysM Cre(+) Ifnar(f/f)) did not sustain enhanced disease with OROV or La Crosse virus, a closely related encephalitic orthobunyavirus. In bone marrow chimera studies, recipient irradiated Ifnar(-/-) mice reconstituted with WT hematopoietic cells sustained high levels of OROV replication and liver damage, whereas WT mice reconstituted with Ifnar(-/-) bone marrow were resistant to disease. Collectively, these results establish a dominant protective role for MAVS, IRF-3 and IRF-7, and IFNAR in restricting OROV virus infection and tissue injury, and suggest that IFN signaling in non-myeloid cells contributes to the host defense against orthobunyaviruses. Oropouche virus (OROV) is an emerging arthropod-transmitted orthobunyavirus that causes episodic outbreaks of a debilitating febrile illness in humans in countries of South and Central America. The continued expansion of the range and number of its arthropod vectors increases the likelihood that OROV will spread into new regions. At present, the pathogenesis of OROV in humans or other vertebrate animals remains poorly understood. To define cellular mechanisms of control of OROV infection, we performed infection studies in a series of primary cells and mice that were deficient in key innate immune genes involved in pathogen recognition and control. Our results establish that a MAVS-dependent type I IFN signaling pathway has a dominant role in restricting OROV infection and pathogenesis in vivo.

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Na região estuarina da Lagoa dos Patos, o siri-azul Callinectes sapidus Rathbun, 1869 é o mais abundante dentre as espécies do gênero. Apesar do siri-azul exercer influência sobre as comunidades bentônicas, por ser considerado um predador do topo da cadeia alimentar, não existem muitos estudos sobre aspectos ecológicos, inclusive sobre a composição e variabilidade sazonal de sua dieta natural, neste estuário. O objetivo principal deste estudo foi investigar a composição da dieta do siri-azul, evidenciando possíveis relações com a comunidade bentônica da região estuarina da Lagoa dos Patos. O período de estudo foi de março de 2003 a março de 2004, com coletas bimestrais. Os organismos foram coletados com auxílio de rede de arrasto de fundo, com malha de 13 mm entre nós opostos. Ainda em campo os animais foram fixados em formol 10%. Após a coleta os animais foram separados quanto ao sexo, medidos (largura e comprimento da carapaça - cm) e pesados (peso - g). Após a triagem, os animais foram dissecados e os intestinos retirados e pesados. As análises dos conteúdos alimentares dos siris demonstraram que os hábitos alimentares são diversificados, constituindo-se principalmente de invertebrados bentônicos. O item encontrado com maior freqüência foi Detrito, seguido pelo molusco filtrador Erodona mactroides Bosc, 1802 (Erodonidae). Crustáceos da classe Ostracoda e grãos de areia foram importantes componentes dos conteúdos dos intestinos anteriores, sendo que areia não foi considerada como item alimentar, propriamente dito. Também foram encontradas cerdas e mandíbulas de poliquetos, além de sementes das macrófitas Ruppia maritima L. (Potamogatonaceae) e Zannichellia palustris L. (Potamogatonaceae). Este estudo serve como subsídio para medidas de proteção e conservação da população do siri-azul, bem como caracteriza relações tróficas com comunidades bentônicas do estuário da Lagoa dos Patos.

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Artikel i konferensrapport.

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Este documento tiene como propósito reunir y analizar el universo de información disponible al respecto del proceso de Lanzamiento de la Marca Davivienda en tres mercados Centroamericanos: Costa Rica, El Salvador y Honduras y así, lograr aprovechar al máximo las experiencias y lecciones aprendidas por la entidad durante este período. Para este propósito, la estructura del trabajo consta de un marco teórico que contempla las teorías sobre el posicionamiento de marca, procediendo a un estudio de caso formal. Este estudio se compone inicialmente de la descripción del Banco Davivienda y los países en los que la entidad ingresó tras la adquisición de la operación de HSBC. Posteriormente, se analiza el proceso del Lanzamiento de Marca desde la formulación e implementación de la estrategia hasta la evaluación y análisis de los resultados obtenidos. Por último, se presentan las conclusiones y recomendaciones con base en la teoría, resultados y aprendizajes.

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El presente trabajo pretende investigar y analizar la utilidad de las relaciones estratégicas comunitarias y el marketing en el sector de extracción de petróleo crudo y gas natural. El mercadeo juega un papel importante a la hora de vender cualquier tipo de producto o servicio. Dependiendo de las características de cada sector, las estrategias de mercadeo pueden llegar a ser más o menos útiles y/o efectivas que otras. Por esta razón, esta investigación pretende analizar la utilidad de las estrategias de marketing comunitario y marketing en el sector de extracción de petróleo crudo y gas natural. La forma de llegar a esa respuesta, puede hallarse por medio de tres caminos: el primero de ellos es encontrar y analizar las características del sector, el segundo es identificar cuáles son las estrategias que están utilizando las empresas que operan este campo, y por último, consistiría en analizar la utilidad de integrar el concepto de relación estratégica comunitaria y marketing al sector de extracción de petróleo crudo y gas natural, en cuanto a los beneficios que el marketing comunitario le traería al sector de interés. El sector de petróleo crudo y gas natural es uno de los más importantes en la economía global y sus clientes son numerosos y totalmente heterogéneos. El mercadeo se vuelve muy complejo para esta industria ya que al tener tipos de clientes tan distintos se dificulta alcanzar las expectativas de cada uno de ellos con una misma estrategia y por supuesto la forma de vender un producto es más compleja. Estos factores mencionados anteriormente están generando relaciones entre empresas y clientes totalmente transaccionales de corto plazo, y es ahí donde se cree que la inclusión de mercadeo relacional y estrategias de mercadeo relacional pueden ser de utilidad para el sector, generando desarrollo y beneficios mutuos tanto para clientes como empresas.

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Con la creciente popularidad de las soluciones de IT como factor clave para aumentar la competitividad y la creación de valor para las empresas, la necesidad de invertir en proyectos de IT se incrementa considerablemente. La limitación de los recursos como un obstáculo para invertir ha obligado a las empresas a buscar metodologías para seleccionar y priorizar proyectos, asegurándose de que las decisiones que se toman son aquellas que van alineadas con las estrategias corporativas para asegurar la creación de valor y la maximización de los beneficios. Esta tesis proporciona los fundamentos para la implementación del Portafolio de dirección de Proyectos de IT (IT PPM) como una metodología eficaz para la gestión de proyectos basados en IT, y una herramienta para proporcionar criterios claros para los directores ejecutivos para la toma de decisiones. El documento proporciona la información acerca de cómo implementar el IT PPM en siete pasos, el análisis de los procesos y las funciones necesarias para su ejecución exitosa. Además, proporciona diferentes métodos y criterios para la selección y priorización de proyectos. Después de la parte teórica donde se describe el IT PPM, la tesis aporta un análisis del estudio de caso de una empresa farmacéutica. La empresa ya cuenta con un departamento de gestión de proyectos, pero se encontró la necesidad de implementar el IT PPM debido a su amplia cobertura de procesos End-to-End en Proyectos de IT, y la manera de asegurar la maximización de los beneficios. Con la investigación teórica y el análisis del estudio de caso, la tesis concluye con una definición práctica de un modelo aproximado IT PPM como una recomendación para su implementación en el Departamento de Gestión de Proyectos.

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This study investigates flash flood forecast and warning communication, interpretation, and decision making, using data from a survey of 418 members of the public in Boulder, Colorado, USA. Respondents to the public survey varied in their perceptions and understandings of flash flood risks in Boulder, and some had misconceptions about flash flood risks, such as the safety of crossing fast-flowing water. About 6% of respondents indicated consistent reversals of US watch-warning alert terminology. However, more in-depth analysis illustrates the multi-dimensional, situationally dependent meanings of flash flood alerts, as well as the importance of evaluating interpretation and use of warning information along with alert terminology. Some public respondents estimated low likelihoods of flash flooding given a flash flood warning; these were associated with lower anticipated likelihood of taking protective action given a warning. Protective action intentions were also lower among respondents who had less trust in flash flood warnings, those who had not made prior preparations for flash flooding, and those who believed themselves to be safer from flash flooding. Additional analysis, using open-ended survey questions about responses to warnings, elucidates the complex, contextual nature of protective decision making during flash flood threats. These findings suggest that warnings can play an important role not only by notifying people that there is a threat and helping motivate people to take protective action, but also by helping people evaluate what actions to take given their situation.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Little information is available related to adolescent calcium intake and relationships with injuries they might suffer from sport participation. To determine calcium intake of high school athletes, to assess their self reported injury rates, and to examine the relationship between the two over a 12 month period of time. Participants received a questionnaire at their school and completed it anywhere they found convenient. Adolescent athletes in the Lincoln Public School system (n=43) that participated in at least one sport in the past year. Four age groups participated in the study with sixteen year olds having a significantly higher calcium intake at 1297 mg that of fourteen year olds. A variety of sports were represented with largest number of respondents participating in baseball/or softball at (55%). The next most played sport was basketball at (18%). Median total diet calcium was 1144.5 mg with a mean of 1182 mg + 567 mg. For the frequency of injuries that caused a missed practice or game in the past year, ankle injuries were the most common (25%). Knee injuries were the second most common (17%), followed closely by hand injuries (8%). Mean total diet calcium of athletes with five or more injuries that caused a missed practice or game was significantly higher at 1966 mg (P<.05) than athletes mean diet calcium with zero, one, two, and three injuries. Total milk calcium of those who reported three injuries that resulted in broken or fractured bones or dislocated joints was significantly higher (P<.05) at 1286 mg of total milk calcium than those who reported having zero, one, or two breaks or fractures. Athletes with higher calcium intakes have a higher number of reported injuries. This may be the result of increased vigorous activity which leads to increased calorie and calcium consumption. More importantly, this increased activity leads to an increased chance of injury. The greater calcium intake correlated with greater number of injuries may also be because of third parties advising the athletes who get injured to drink more milk and get more calcium in their diets because they have been injuries already.

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Background Although CD4 cell count monitoring is used to decide when to start antiretroviral therapy in patients with HIV-1 infection, there are no evidence-based recommendations regarding its optimal frequency. It is common practice to monitor every 3 to 6 months, often coupled with viral load monitoring. We developed rules to guide frequency of CD4 cell count monitoring in HIV infection before starting antiretroviral therapy, which we validated retrospectively in patients from the Swiss HIV Cohort Study. Methodology/Principal Findings We built up two prediction rules (“Snap-shot rule” for a single sample and “Track-shot rule” for multiple determinations) based on a systematic review of published longitudinal analyses of CD4 cell count trajectories. We applied the rules in 2608 untreated patients to classify their 18 061 CD4 counts as either justifiable or superfluous, according to their prior ≥5% or <5% chance of meeting predetermined thresholds for starting treatment. The percentage of measurements that both rules falsely deemed superfluous never exceeded 5%. Superfluous CD4 determinations represented 4%, 11%, and 39% of all actual determinations for treatment thresholds of 500, 350, and 200×106/L, respectively. The Track-shot rule was only marginally superior to the Snap-shot rule. Both rules lose usefulness for CD4 counts coming near to treatment threshold. Conclusions/Significance Frequent CD4 count monitoring of patients with CD4 counts well above the threshold for initiating therapy is unlikely to identify patients who require therapy. It appears sufficient to measure CD4 cell count 1 year after a count >650 for a threshold of 200, >900 for 350, or >1150 for 500×106/L, respectively. When CD4 counts fall below these limits, increased monitoring frequency becomes advisable. These rules offer guidance for efficient CD4 monitoring, particularly in resource-limited settings.

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Surgery and other invasive therapies are complex interventions, the assessment of which is challenged by factors that depend on operator, team, and setting, such as learning curves, quality variations, and perception of equipoise. We propose recommendations for the assessment of surgery based on a five-stage description of the surgical development process. We also encourage the widespread use of prospective databases and registries. Reports of new techniques should be registered as a professional duty, anonymously if necessary when outcomes are adverse. Case series studies should be replaced by prospective development studies for early technical modifications and by prospective research databases for later pre-trial evaluation. Protocols for these studies should be registered publicly. Statistical process control techniques can be useful in both early and late assessment. Randomised trials should be used whenever possible to investigate efficacy, but adequate pre-trial data are essential to allow power calculations, clarify the definition and indications of the intervention, and develop quality measures. Difficulties in doing randomised clinical trials should be addressed by measures to evaluate learning curves and alleviate equipoise problems. Alternative prospective designs, such as interrupted time series studies, should be used when randomised trials are not feasible. Established procedures should be monitored with prospective databases to analyse outcome variations and to identify late and rare events. Achievement of improved design, conduct, and reporting of surgical research will need concerted action by editors, funders of health care and research, regulatory bodies, and professional societies.

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Research on surgical interventions is associated with several methodological and practical challenges of which few, if any, apply only to surgery. However, surgical evaluation is especially demanding because many of these challenges coincide. In this report, the second of three on surgical innovation and evaluation, we discuss obstacles related to the study design of randomised controlled trials and non-randomised studies assessing surgical interventions. We also describe the issues related to the nature of surgical procedures-for example, their complexity, surgeon-related factors, and the range of outcomes. Although difficult, surgical evaluation is achievable and necessary. Solutions tailored to surgical research and a framework for generating evidence on which to base surgical practice are essential.