Efficacy of Combination of Immunotherapies in a Murine in a Murine Squamous Cell Carcinoma Model

Introduction: Head and neck squamous cell carcinomas (HNSCCs) are a type of neoplasm found in the epithelium of the oral cavity, oropharynx, nasopharynx, larynx, or hypopharynx. Recent evidence has demonstrated that 70-90% of HNSCC are associated with Human Papillomavirus (HPV), particularly strain 16 producing oncogenic proteins E6/E7. Currently, HNSCCs are treated with surgery, chemotherapy, and radiation, however immunotherapy with immune checkpoint (PD-1) blocking agents promises to improve outcomes in HNSCC. Objective: This study examined the therapeutic effects of dual and triple combination immunotherapies in a mouse model of HPV-associated HNSCC. Methods: Treatment modalities included a tumor vaccine (attenuated Listeria monocytogenes based vaccine encoding HPV16 E6/E7 (AXAL)), an immune checkpoint inhibitor targeting PD1 (RMP1-14) and topical subtherapeutic radiation. Mice were injected subcutaneously with tumor cells expressing HPV16 E6/E7 (TC-1). When tumors were established, mice were vaccinated with AXAL (3 injections) either alone and/or with anti-PDi and/or with a single dose of radiation. Results: Partial responses were observed in some mice receiving dual combination therapies. Most mice treated with triple immunotherapy revealed complete tumor regression. Discussion: Combination immunotherapy is effective in the TC-1 HNSCC model system. The results obtained set the stage for investing immune mechanism underpinning treatment-associated tumor regression

Evaluación de la estrategia “educadores de pares” para prevención de infecciones de transmisión sexual y VIH entre escolares de Sullana y Ayabaca

Las infecciones de transmisión sexual y la epidemia producida por el virus de inmunodeficiencia humana (VIH), causante del síndrome de inmunodeficiencia adquirida (SIDA), se extiende inexorable e indeteniblemente hacia todos los rincones del mundo y constituye un gran reto para la supervivencia de la humanidad. Una estrategia implementada para controlar y prevenir esta epidemia es la de “educadores pares” para la población vulnerable (hombres que tienen sexo con hombres y trabajadoras sexuales). Es una estrategia efectiva para la prevención de VIH en población de elevada prevalencia, sin embargo, no existe una evaluación de esta estrategia en grupos de orientadores pares de adolescentes y jóvenes. La problemática que envuelve a las ITS y al VIH/SIDA demanda la articulación de los agentes que trabajan e inciden en la prevención, acción y propagación de los mismos. Es un problema de salud pública, ya que las conductas de riesgo en adolescentes y jóvenes incrementan la posibilidad de ITS y de contagio con el VIH/SIDA, manteniendo y propiciando el desarrollo de la epidemia con secuelas de morbilidad y mortalidad, consume recursos públicos ya que las personas infectadas demandan y requieren de diagnóstico, tratamiento paliativo y prevención secundaria haciendo que el Estado deje de lado otras prioridades. Afecta el bienestar social y familiar debido a la destrucción de los proyectos de vida personales y familiares

Polifarmacia psiquiátrica en personas con esquizofrenia en un establecimiento público de salud mental en Lima

Objetivos: El presente estudio busca identificar retrospectivamente la prevalencia de polifarmacia psiquiátrica en pacientes con el diagnóstico de esquizofrenia que reciben atención ambulatoria en el Instituto Nacional de Salud Mental “Honorio Delgado – Hideyo Noguchi” (Lima, Perú). Material y Métodos: Se revisaron 430 historias clínicas de pacientes con diagnóstico único de esquizofrenia, supuestamente estables clínicamente, atendidos en Consulta Externa de la Dirección de Adultos o en el Módulo de Intervención Breve del Instituto, durante el año 2016. Resultados: El 84,4% de la muestra recibió más de un psicofármaco, con un promedio de 3,0 psicofármacos por paciente; el 40,5% recibió más de un antipsicótico, con un promedio de 1,5 antipsicóticos por paciente; al 96,2% de los que recibían antipsicóticos de depósito, se agregó uno o más psicofármacos, y al 86,2%, uno o más antipsicóticos por vía oral. Como psicofármacos adicionales, el 50,9% tomaba una benzodiacepina, el 47,0% un anticolinérgico, el 24,4% un antidepresivo inhibidor de la recaptación de serotonina, y el 21,2%, por lo menos un estabilizador del ánimo. El número de psicofármacos en general y antipsicóticos en particular se asoció significativamente con hospitalizaciones previas, antecedente de terapia electroconvulsiva, uso de antipsicóticos de primera generación y uso de antipsicóticos de depósito. Conclusiones: Se encontró una elevada prevalencia de polifarmacia psiquiátrica en la población estudiada, lo que debe motivar la revisión de las guías de práctica clínica y la elaboración de normas que regulen el uso de psicofármacos

Kaizen: estudo de caso na empresa J. Rascão, Lda

Na situação económica atual torna-se crucial para as empresas adaptarem-se de forma rápida a um meio envolvente dinâmico e em constante mutação, de forma a obterem uma vantagem competitiva. Esta vantagem pode ser obtida através da adoção de técnicas subjacentes ao kaizen, que lhes permitem reduzir desperdícios, otimizando os seus recursos, e obter níveis de qualidade e de produtividade maiores, sem que isso implique custos elevados. Este projeto teve lugar na empresa J. Rascão Lda., do sector metalomecânico, em resposta à necessidade que esta sentiu em melhorar o seu processo produtivo, reaproveitando os seus recursos. Com este trabalho pretende-se expor as três técnicas características do kaizen, que podem contribuir de forma significativa para uma melhor gestão de uma empresa. Pretende-se também averiguar a aplicabilidade das mesmas no contexto de uma empresa do sector metalomecânico, assim como analisar o impacto e aceitação que estas poderão ter no quotidiano da empresa. Foi possível concluir, através deste projeto, que o fator que caracteriza o kaizen como único, é a existência de uma cultura própria, constituindo-se a sua ausência numa das causas para a dificuldade de implementação das técnicas, na realidade concreta. Prova disso foram as técnicas implementadas, a curto prazo, que apesar de terem surtido efeitos positivos, não foi possível incutir na empresa, em causa, o “espírito” kaizen

Multi-Source Glacial Lake Outburst Flood Hazard Assessment and Mapping for Huaraz, Cordillera Blanca, Peru

The Quillcay catchment in the Cordillera Blanca, Peru, contains several glacial lakes, including Lakes Palcacocha (with a volume of 17 × 106 m3), Tullparaju (12 × 106 m3), and Cuchillacocha (2 × 106 m3). In 1941 an outburst of Lake Palcacocha, in one of the deadliest historical glacial lake outburst floods (GLOF) worldwide, destroyed large parts of the city of Huaraz, located in the lowermost part of the catchment. Since this outburst, glaciers, and glacial lakes in Quillcay catchment have undergone drastic changes, including a volume increase of Lake Palcacocha between around 1990 and 2010 by a factor of 34. In parallel, the population of Huaraz grew exponentially to more than 120,000 inhabitants nowadays, making a comprehensive assessment and mapping of GLOF hazards for the Quillcay catchment and the city of Huaraz indispensable. Here we present a scenario-based multi-source GLOF hazard mapping, applying a chain of interacting numerical models to simulate involved cascading mass movement processes. Susceptibility assessments for rock-ice avalanches and breach formation at moraine dams were used to define scenarios of different magnitudes and related probabilities, which are then simulated by corresponding mass movement models. The evaluation revealed, that (1) the three investigated lakes pose a significant GLOF hazard to the Quillcay Catchment and the city of Huaraz, (2) in some scenarios the highest hazard originates from the lake with the smallest volume (Cuchillacocha), and (3) current moraine characteristics of Lake Palcacocha cannot be compared to the situation prior and during the 1941 outburst. Results of outburst floods obtained by the RAMMS model were then converted into intensity maps and corresponding hazard levels according to national and international standards, and eventually combined into the GLOF hazard map for the entire Quillcay catchment, including the urban area of Huaraz. Besides technical aspects of such a multi-source model-based hazard mapping, special attention is also paid to approval and dissemination aspects in a complex institutional context. Finally, some general conclusions are drawn and recommendations are given, that go beyond the presented case of the Quillcay Catchment

Limits to the energy resolution of a single Air Cherenkov Telescope at low energies

The photon density on the ground is a fundamental quantity in all experiments based on Cherenkov light measurements, e.g. in the Imaging Air Cherenkov Telescopes (IACT). IACT's are commonly and successfully used in order to search and study Very High Energy (VHE) gamma-ray sources. Difficulties with separating primary photons from primary hadrons (mostly protons) in Cherenkov experiments become larger at lower energies. I have calculated longitudinal and lateral density distributions and their fluctuations at low energies basing on Monte Carlo simulations (for vertical gamma cascades and protonic showers) to check the influence of the detector parameters on the possible measurement. Relative density fluctuations are significantly higher in proton than in photon induced showers. Taking into account the limited detector field of view (FOV) implies the changes of these calculated distributions for both types of primary particles and causes an enlargement in relative fluctuations. Absorption due to Rayleigh and Mie scattering has an impact on mean values but does not change relative fluctuations. The total number of Cherenkov photons is more sensitive to the observation height in gamma cascades than in proton showers at low primary energies. The relative fluctuations of the density do not depend on the reflector size in the investigated size range (from 240 m^2 up to 960 m^2). This implies that a single telescope with a mirror area larger than that of the MAGIC telescope cannot achieve better energy resolution than estimated and presented in this paper. The correlations between longitudinal and lateral distributions are much more pronounced for primary gamma-ray than for primary proton showers.Comment: 21 pages, 11 figures, accepted for publication in Journal of Physics

Prospective monitoring improves outcomes of primary total hip replacement: a cohort study

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Kidney disease pathways, options and decisions: an environmental scan of international patient decision aids

Background: Conservative management is recognized as an acceptable treatment for people with worsening chronic kidney disease; however, patients consistently report they lack understanding about their changing disease state and feel unsupported in making shared decisions about future treatment. The purpose of this review was to critically evaluate patient decision aids (PtDAs) developed to support patient–professional shared decision-making between dialysis and conservative management treatment pathways. Methods: We performed a systematic review of resources accessible in English using environmental scan methods. Data sources included online databases of research publications, repositories for clinical guidelines, research projects and PtDAs, international PtDA expert lists and reference lists from relevant publications. The resource selection was from 56 screened records; 17 PtDAs were included. A data extraction sheet was applied to all eligible resources, eliciting resource characteristics, decision architecture to boost/bias thinking, indicators of quality such as International Standards for Patient Decision Aids Standards checklist and engagement with health services. Results: PtDAs were developed in five countries; eleven were publically available via the Internet. Treatment options described were dialysis (n = 17), conservative management (n = 9) and transplant (n = 5). Eight resources signposted conservative management as an option rather than an active choice. Ten different labels across 14 resources were used to name ‘conservative management’. The readability of the resources was good. Six publications detail decision aid development and/or evaluation research. Using PtDAs improved treatment decision-making by patients. Only resources identified as PtDAs and available in English were included. Conclusions: PtDAs are used by some services to support patients choosing between dialysis options or end-of-life options. PtDAs developed to proactively support people making informed decisions between conservative management and dialysis treatments are likely to enable services to meet current best practice

Gargalos nas cadeias de produção.

Introdução. Antes da Fazenda. Defensivos químicos e biológicos no Brasil. Fertilizantes e corretivos. Biotecnologia, Softwares agricultura digital/ precisão. Conectividade e a falta de comunicação de dados nas propriedades rurais. Dentro da Fazenda. Custos de produção e melhoria do pacote tecnológico. Depois da Fazenda. Comercialização nacional e internacional. Temas Transversais. Falta de energia de qualidade nas propriedades rurais. Rastreabilidade. Aspectos da logística. Capacitação e extensão rural