Protocol for the isotoxic intensity modulated radiotherapy (IMRT) in stage III non-small cell lung cancer (NSCLC): a feasibility study.

Introduction The majority of stage III patients with non-small cell lung cancer (NSCLC) are unsuitable for concurrent chemoradiotherapy, the non-surgical gold standard of care. As the alternative treatment options of sequential chemoradiotherapy and radiotherapy alone are associated with high local failure rates, various intensification strategies have been employed. There is evidence to suggest that altered fractionation using hyperfractionation, acceleration, dose escalation, and individualisation may be of benefit. The MAASTRO group have pioneered the concept of ‘isotoxic’ radiotherapy allowing for individualised dose escalation using hyperfractionated accelerated radiotherapy based on predefined normal tissue constraints. This study aims to evaluate whether delivering isotoxic radiotherapy using intensity modulated radiotherapy (IMRT) is achievable.

Methods and analysis Isotoxic IMRT is a multicentre feasibility study. From June 2014, a total of 35 patients from 7 UK centres, with a proven histological or cytological diagnosis of inoperable NSCLC, unsuitable for concurrent chemoradiotherapy will be recruited. A minimum of 2 cycles of induction chemotherapy is mandated before starting isotoxic radiotherapy. The dose of radiation will be increased until one or more of the organs at risk tolerance or the maximum dose of 79.2 Gy is reached. The primary end point is feasibility, with accrual rates, local control and overall survival our secondary end points. Patients will be followed up for 5 years.

Ethics and dissemination The study has received ethical approval (REC reference: 13/NW/0480) from the National Research Ethics Service (NRES) Committee North West—Greater Manchester South. The trial is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice (GCP). The trial results will be published in a peer-reviewed journal and presented internationally.

Trial registration number NCT01836692; Pre-results.

Potential strategies for the eradication of multi-drug resistant Gram-negative bacterial infections

Antimicrobial resistance is one of the leading threats to society. The increasing burden of multidrug-resistant Gram-negative infection is particularly concerning as such bacteria are demonstrating resistance to nearly all currently licensed therapies. Various strategies have been hypothesized to treat multidrug-resistant Gram-negative infections including: targeting the Gram-negative outer membrane; neutralization of lipopolysaccharide; inhibition of bacterial efflux pumps and prevention of protein folding. Silver and silver nanoparticles, fusogenic liposomes and nanotubes are potential strategies for extending the activity of licensed, Gram-positive selective, antibiotics to Gram-negatives. This may serve as a strategy to fill the current void in pharmaceutical development in the short term. This review outlines the most promising strategies that could be implemented to solve the threat of multidrug-resistant Gram-negative infections

Consensus of Official Position of IOF/ISCD FRAX Initiatives in Asia-Pacific Region.

The fracture risk assessment tool (FRAX(®)) has been developed for the identification of individuals with high risk of fracture in whom treatment to prevent fractures would be appropriate. FRAX models are not yet available for all countries or ethnicities, but surrogate models can be used within regions with similar fracture risk. The International Society for Clinical Densitometry (ISCD) and International Osteoporosis Foundation (IOF) are nonprofit multidisciplinary international professional organizations. Their visions are to advance the awareness, education, prevention, and treatment of osteoporosis. In November 2010, the IOF/ISCD FRAX initiative was held in Bucharest, bringing together international experts to review and create evidence-based official positions guiding clinicians for the practical use of FRAX. A consensus meeting of the Asia-Pacific (AP) Panel of the ISCD recently reviewed the most current Official Positions of the Joint Official Positions of ISCD and IOF on FRAX in view of the different population characteristics and health standards in the AP regions. The reviewed position statements included not only the key spectrum of positions but also unique concerns in AP regions.

A Meta-Analysis of Trabecular Bone Score in Fracture Risk Prediction and Its Relationship to FRAX.

Trabecular bone score (TBS) is a gray-level textural index of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images. TBS is a bone mineral density (BMD)-independent predictor of fracture risk. The objective of this meta-analysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine their combined performance by adjusting the FRAX probability for TBS. We utilized individual-level data from 17,809 men and women in 14 prospective population-based cohorts. Baseline evaluation included TBS and the FRAX risk variables, and outcomes during follow-up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities, and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1 SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% confidence interval [CI] 1.35-1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10-year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR = 1.32, 95% CI 1.24-1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95% CI 1.65-1.87 versus 1.70, 95% CI 1.60-1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines. © 2015 American Society for Bone and Mineral Research.

Efectividad del tratamiento farmacológico de la agresividad en pacientes con trastorno límite de la personalidad. Revisión sistemática

Introducción: el Trastorno Límite de la Personalidad afecta del 2% al 6% de los adultos en Estados Unidos. Es una condición de alta relevancia dentro de las patologías psiquiátricas debido a características como impulsividad, inestabilidad en las relaciones interpersonales, disregulación en el estado de ánimo y comportamiento agresivo. Esto determina un impacto negativo en la funcionalidad del individuo siendo la agresividad contra sí mismo o contra otras personas uno de sus componentes claves. Métodos: Revisión sistemática de la literatura de artículos de bases de datos y búsqueda manual de revistas relacionadas que aportaran la mejor evidencia con el fin de encontrar estudios que evaluaran, con instrumentos objetivos, los tratamientos farmacológicos disponibles para el manejo de la agresividad en el TLP .Se evaluó calidad metodológica y los estudios se organizaron en tablas de evidencia. Resultados: La búsqueda arrojo 1081 artículos de los cuales se seleccionaron 52 como potenciales y cinco fueron incluidos en esta revisión. Se clasificaron como nivel de evidencia Ib. El topiramato, el aripiprazol, el divalproato y la fluoxetina mostraron mejores resultados que el placebo especialmente en agresividad e impulsividad. El topiramato fue asociado con pérdida de peso. Los medicamentos fueron seguros y bien tolerados. Discusión: Los medicamentos evaluados mostraron ser mejores que placebo. La diversidad en las escalas utilizadas genera complejidad en la interpretación de resultados. Conclusión: La evidencia sugiere que el tratamiento farmacológico es efectivo en síntomas como agresividad e impulsividad comparado con placebo. Deben considerarse estudios que evalúen combinaciones de fármacos y psicoterapia.

Mental health of internally displaced preschool children: a cross-sectional study conducted in Bogotá, Colombia

A causa de los conflictos armados, como el de Colombia, se han desplazado por la fuerza a millones de personas, entre ellas una importante parte de la población infantil. Este estudio tuvo como objetivo evaluar la salud mental de los niños desplazados internos en edad preescolar en Bogotá Colombia, e identificar los determinantes de la salud mental en estos niños. Métodos: Estudio transversal realizado entre 279 niños que asisten a cuatro jardines infantiles en un barrio marginal de Bogotá. La salud mental infantil se evaluó con el instrumento validado de Comportamiento Infantil (CBCL) 1,5-5 años, aplicados a padres y cuidadores. Se realizo un análisis univariado y multivariado de regresión logística para evaluar la asociación entre el desplazamiento y la salud mental de los niños y para identificar las relaciones con la salud mental en los niños desplazados. Resultados: los Niños desplazados (n = 90) se identificaron con más frecuencia sobre los puntos de corte límite para las escalas CBCL que los no desplazados (n = 189) (por ejemplo, problemas totales 46,7 vs 22,8%;p \ 0,001). La asociación entre el desplazamiento y la presencia de problemas CBCL totales se mantuvo después del ajuste por factores socio-demográficos (OR Ajustado 3.3 del 95%: 1,5; 6,9). Donde la salud mental del cuidador explica en parte la asociación. En los niños desplazados, la salud mental del cuidador (p \ 0,01) y el funcionamiento familiar (p \ 0,01) se asociaron independientemente con la salud mental de los niños. La exposición a eventos traumáticos y el apoyo social también se asociaron con la salud mental del niño, sin embargo, las asociaciones no fueron independientes. Conclusión: En este barrio marginal de Bogotá, los niños en edad preescolar registrados como desplazados internos presentan peor salud mental que los no desplazados. El funcionamiento familiar y la salud mental del cuidador fueron fuerte e independientemente asociados con la salud mental de los niños y niñas desplazados.

Variación en la resistencia al flujo de los tubos endotraqueales pediátricos modificando su longitud

Introducción: Se conocen los beneficios del uso de los tubos endotraqueales con neumotaponador, aunque dicha práctica tiene un impacto sobre el trabajo respiratorio durante el acto anestésico sin embargo se propone estudiar las consecuencias físicas de la variación en la longitud de los tubos para compensar dicha perdida de flujo, con base en la ley de Hagen-Poiseuille. Metodología: Se realizó un estudio experimental in vitro, en el cual se realizaron mediciones repetidas de flujo, variando la longitud y diámetro de diferentes tubos endotraqueales pediátricos (desde calibre 3.5mm hasta 6.5mm), con longitudes de 20cm, 15 cm, 10 cm y manteniendo su longitud original. Se analizaron los datos con el fin de medir el impacto sobre el flujo. Resultados: A pesar que los resultados muestran diferencias estadísticamente significativas (p0,000), la variación en la longitud de los tubos endotraqueales pediátricos tiene mucho menor impacto sobre la variación en el flujo, que la modificación del diámetro. Discusión: Si bien la práctica de acortar la longitud de un tubo endotraqueal pediátrico puede ayudar a reducir el espacio muerto y la retención de CO2, el impacto que tiene sobre el flujo es poco. Cuando se trata de disminuir el trabajo respiratorio de un niño en ventilación espontánea durante el acto anestésico, se debe escoger de forma apropiada el calibre de tubo correspondiente para la edad.

Docentes globales : un modelo para el desarrollo de la competencia intercultural on-line.

Resumen tomado de la publicación. - El artículo forma parte del monográfico de la revista dedicado a: Alfabetización mediática en contextos múltiples

A razão da retórica : hermenêutica, pragmatismo e a lógica argumentativa no discurso econômico

Esta dissertação tem como objetivo defender a perspectiva da existência de uma lógica por trás dos discursos retórico-persuasivos – tal como inaugurada por McCloskey (1983) e Arida (1983) dentro da ciência econômica. O objetivo é demonstrar a completa inadequação de se confundir filosoficamente “retoricismo” com “irracionalismo”, pois, de acordo com nossa interpretação, nem McCloskey nem Arida propõem que não se deva utilizar critérios racionais para validação de teorias econômicas. O que eles propõem, a nosso ver, é que não se deva compreender a história do pensamento econômico e a própria teoria econômica atual como resultado de uma evolução apodíctica epistemologicamente mediada por evidências (sejam elas empíricas ou dedutivas). Isto, no entanto não implica numa desconsideração da “razão” por completo – a não ser que se entenda a “razão” por um prisma estritamente epistemológico; o que não nos parece muito razoável. Sendo assim, procuramos desenvolver ao longo do trabalho argumentos filosóficos oriundos das perspectivas hermenêuticas de: Heidegger, Gadamar, Habermas e Ricoeur, além do pragmatismo de Richard Rorty; com o intuito de relaciona-los com as perspectivas retóricas de McCloskey e Arida; buscando, mais especificamente, demonstrar a fundamentação racional da perspectiva retórica em relação à filosofia contemporânea, e contribuir com o debate retórico na economia a partir de uma tentativa de aproximação entre as perspectivas hermenêuticas – mais especificamente de Habermas e Ricoeur – e a perspectiva retórica de Arida; além de procurar uma melhor explicação e relação entre a filosofia hermenêutica-pragmática, e a perspectiva da “racionalidade prática” presente na ‘nova retórica” de Chaïm Perelman.

Two and a Half Cheers for the Midwestern Bourgeoisie: Role of the Virtues in Tempering Business Decisions

A recent book (The Bourgeois Virtues: Ethics for an Age of Commerce, D. N. McCloskey), raises the matter of the role of the virtues in business and economic choice, arguing that capitalism can indeed, be virtuous or at least better than the alternative(s). This argument is especially timely in light of the apparent excesses on Wall Street and in some banking/financial institutions. Excessive greed and often the lack of business ethics contributed in substantive ways to the financial crisis and near economic meltdown we have been experiencing. As McCloskey, (2006, pp. 1-2) argues (in setting the stage for the complex argument made in this 616-page book!): “The book … is directed toward you who are suspicious of the phrase ‘bourgeois virtues,’ pretty sure that it is a contradiction in terms. And the book is directed, with less optimism about changing their minds, toward you who think the phrase is worse: a lie. ‘Bourgeois virtues’ is neither. The claim here is that modern capitalism does not need to be offset to be good. Capitalism can on the contrary be virtuous. In a fallen world bourgeois life is not perfect. But it’s better than any available alternative. American capitalism needs to be inspirited, moralized, completed. Two and a half cheers for the Midwestern bourgeoisie (middle-class, small business owners…. yet)… Many a businessman is an ethical shell or worse. Even the virtues of the bourgeoisie, … do not lead straight to heaven.”

Mythologizing Greed and Betrayal in the Strait of Magellan in Juan de Miramontes' Armas Antarticas

Taking as a starting point Antonio Sanchez Jimenez's recent work on the myth of Jason in Lope de Vega's El Vellocino de Oro, this article examines the myths of Jason and Leander in Juan de Miramontes Zuazola's epic, Armas antarticas (1608-1609). After exploring the explicit allusions to the myths in the epic, I analyse an implicit reference to Leander in the portrayal of Tome Hernandez, the only survivor of the failed sixteenth-century Spanish settlements in the Strait of Magellan. As it turns out, Hernandez was rescued by the English pirate, Thomas Cavendish. In evoking the myth of Leander on the southern coast of Chile, Armas antarticas recalls Alonso de Ercilla's self-description in La Araucana (1569, 78, 89) as analysed by Ricardo Padron. However, I contend that the representation of Hernandez is best understood in comparison to Juan Boscan's Leandro (1543), the fullest and most widely disseminated Spanish version of the tale in the sixteenth century. Appealing to the Leander myth allows Armas antarticas to turn away from a focus on the role of greed in colonization. Yet shadows of Jason still lurk behind the portrayal of Hernandez, which raise other serious ethical questions for the Spanish Empire concerning piracy and loyalty as these play out in the Strait of Magellan. This essay shows that the poetic portrayal of Hernandez and Cavendish ends up exhibiting the same ambiguities associated with piracy as analysed by Daniel Heller-Roazen.

A meta-analysis of trabecular bone score in fracture risk prediction and its relationship to FRAX

Trabecular bone score (TBS) is a grey-level textural index of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images. TBS is a BMD-independent predictor of fracture risk. The objective of this meta-analysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine their combined performance by adjusting the FRAX probability for TBS. We utilized individual level data from 17,809 men and women in 14 prospective population-based cohorts. Baseline evaluation included TBS and the FRAX risk variables and outcomes during follow up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% CI: 1.35-1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10-year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR 1.32, 95%CI: 1.24-1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95%CI: 1.65, 1.87 vs. 1.70, 95%CI: 1.60-1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines. This article is protected by copyright. All rights reserved.