Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial

BACKGROUND: Prostate cancer might have high radiation-fraction sensitivity that would give a therapeutic advantage to hypofractionated treatment. We present a pre-planned analysis of the efficacy and side-effects of a randomised trial comparing conventional and hypofractionated radiotherapy after 5 years follow-up.

METHODS: CHHiP is a randomised, phase 3, non-inferiority trial that recruited men with localised prostate cancer (pT1b-T3aN0M0). Patients were randomly assigned (1:1:1) to conventional (74 Gy delivered in 37 fractions over 7·4 weeks) or one of two hypofractionated schedules (60 Gy in 20 fractions over 4 weeks or 57 Gy in 19 fractions over 3·8 weeks) all delivered with intensity-modulated techniques. Most patients were given radiotherapy with 3-6 months of neoadjuvant and concurrent androgen suppression. Randomisation was by computer-generated random permuted blocks, stratified by National Comprehensive Cancer Network (NCCN) risk group and radiotherapy treatment centre, and treatment allocation was not masked. The primary endpoint was time to biochemical or clinical failure; the critical hazard ratio (HR) for non-inferiority was 1·208. Analysis was by intention to treat. Long-term follow-up continues. The CHHiP trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN97182923.

FINDINGS: Between Oct 18, 2002, and June 17, 2011, 3216 men were enrolled from 71 centres and randomly assigned (74 Gy group, 1065 patients; 60 Gy group, 1074 patients; 57 Gy group, 1077 patients). Median follow-up was 62·4 months (IQR 53·9-77·0). The proportion of patients who were biochemical or clinical failure free at 5 years was 88·3% (95% CI 86·0-90·2) in the 74 Gy group, 90·6% (88·5-92·3) in the 60 Gy group, and 85·9% (83·4-88·0) in the 57 Gy group. 60 Gy was non-inferior to 74 Gy (HR 0·84 [90% CI 0·68-1·03], pNI=0·0018) but non-inferiority could not be claimed for 57 Gy compared with 74 Gy (HR 1·20 [0·99-1·46], pNI=0·48). Long-term side-effects were similar in the hypofractionated groups compared with the conventional group. There were no significant differences in either the proportion or cumulative incidence of side-effects 5 years after treatment using three clinician-reported as well as patient-reported outcome measures. The estimated cumulative 5 year incidence of Radiation Therapy Oncology Group (RTOG) grade 2 or worse bowel and bladder adverse events was 13·7% (111 events) and 9·1% (66 events) in the 74 Gy group, 11·9% (105 events) and 11·7% (88 events) in the 60 Gy group, 11·3% (95 events) and 6·6% (57 events) in the 57 Gy group, respectively. No treatment-related deaths were reported.

INTERPRETATION: Hypofractionated radiotherapy using 60 Gy in 20 fractions is non-inferior to conventional fractionation using 74 Gy in 37 fractions and is recommended as a new standard of care for external-beam radiotherapy of localised prostate cancer.

FUNDING: Cancer Research UK, Department of Health, and the National Institute for Health Research Cancer Research Network.

Tsunami characteristics along the Peru-Chile trench: analysis of the 2015 Mw8.3 Illapel, the 2014 Mw8.2 iquique and the 2010 Mw8.8 maule tsunamis in the near-field

Tsunamis occur quite frequently following large magnitude earthquakes along the Chilean coast. Most of these earthquakes occur along the Peru-Chile Trench, one of the most seismically active subduction zones of the world. This study aims to understand better the characteristics of the tsunamis triggered along the Peru-Chile Trench. We investigate the tsunamis induced by the Mw8.3 Illapel, the Mw8.2 Iquique and the Mw8.8 Maule Chilean earthquakes that happened on September 16th, 2015, April 1st, 2014 and February 27th, 2010, respectively. The study involves the relation between the co-seismic deformation and the tsunami generation, the near-field tsunami propagation, and the spectral analysis of the recorded tsunami signals in the near-field. We compare the tsunami characteristics to highlight the possible similarities between the three events and, therefore, attempt to distinguish the specific characteristics of the tsunamis occurring along the Peru-Chile Trench. We find that these three earthquakes present faults with important extensions beneath the continent which result in the generation of tsunamis with short wavelengths, relative to the fault widths involved, and with reduced initial potential energy. In addition, the presence of the Chilean continental margin, that includes the shelf of shallow bathymetry and the continental slope, constrains the tsunami propagation and the coastal impact. All these factors contribute to a concentrated local impact but can, on the other hand, reduce the far-field tsunami effects from earthquakes along Peru-Chile Trench.

Cambios globales y el mercado laboral peruano: comercio, legislación, capital humano y empleo

El presente libro contiene los principales aportes al conocimiento del mercado laboral peruano y el diseño de políticas de empleo que se discutieron en la Primera Conferencia de Economía Laboral del Perú, desarrollada en la Universidad del Pacífico. Se incluyen trabajos que, desde las visiones de la economía y el derecho laboral, cubren las áreas de macroeconomía internacional y nacional, instituciones en el mercado de trabajo, formación y retornos al capital humano, y desarrollo de mercados de trabajo regionales.

The Shrine of ʿAbd al-Qādir al-Jīlānī in Baghdad & the Shrine of ʿAbd al-ʿAzīz al-Jīlānī in ʿAqra: Mapping the multiple orientations of two Qādirī Sufi shrines in Iraq

This thesis charts the stakeholder communities, physical environment and daily life of two little studied Qādiriyya Sufi shrines associated with Shaikh ʿAbd al-Qādir al-Jīlānī (1077 – 1165 AD), a 12th century Ḥanbalī Muslim theologian and the posthumous founder of one of the oldest Sufi orders in Islam. The first shrine is based in Baghdad and houses his burial chamber; and the second shrine, on the outskirts of the city of ‘Aqra in the Kurdish region of northern Iraq, is that of his son Shaikh ʿAbd al-ʿAzīz (died 1206 AD). The latter was also known for lecturing in Ḥanbalī theology in the region, and venerated for this as well as his association with Shaikh ʿAbd al-Qādir. Driven by the research question “What shapes the identity orientations of these two Qādiriyya Sufi shrines in modern times?” the findings presented here are the result of field research carried out between November 2009 and February 2014. This field research revealed a complex context in which the two shrines existed and interacted, influenced by both Sufi and non-Sufi stakeholders who identified with and accessed these shrines to satisfy a variety of spiritual and practical needs, which in turn influenced the way each considered and viewed the two shrines from a number of orientations. These overlapping orientations include the Qādirī Sufi entity and the resting place of its patron saint; the orthodox Sunnī mosque with its muftī-imams, who are employed by the Iraqi government; the local Shīʿa community’s neighbourhood saint’s shrine and its destination for spiritual and practical aid; and the local provider of welfare to the poor of the city (soup kitchen, funeral parlour and electricity-generation amongst other services). The research findings also revealed a continuously changing and adapting Qādirī Sufi scene not immune from the national and regional socio-religio-political environments in which the two shrines exist: a non-Sufi national political class vying to influence and manipulate these shrines for their own purposes; and powerful national sectarian factions jostling to do the same. The mixture of stakeholders using and associating with the two shrines were found to be influential shapers of these entities, both physically and spiritually. Through encountering and interacting with each other, most stakeholders contributed to maintaining and rejuvenating the two shrines, but some also sought to adapt and change them driven by their particular orientation’s perspective.

Systematic reviews as a tool for planning and interpreting trials

Background Systematic reviews followed by ameta-analysis are carried out in medical research to combine the results of two or more related studies. Stroke trials have struggled to show beneficial effects and meta-analysis should be used more widely throughout the research process to either speed up the development of useful interventions, or halt more quickly research with hazardous or ineffective interventions. Summary of review. This review summarises the clinical research process and illustrates how and when systematic reviews may be used throughout the development programme. Meta-analyses should be performed after observational studies, preclinical studies in experimental stroke, and after phase I, II, and III clinical trials and phase IV clinical surveillance studies. Although meta-analyses most commonly work with summary data, they may be performed to assess relationships between variables (meta-regression) and, ideally, should utilise individual patient data. Meta-analysis techniques may alsoworkwith ordered categorical outcome data (ordinal meta-analysis) and be used to perform indirect comparisons where original trial data do not exist. Conclusion Systematic review/meta-analyses are powerful tools in medical research and should be used throughout the development of all stroke and other interventions

EVALUACIÓN DE LA PROPUESTA PARA EL ESTABLECIMIENTO DE UN SISTEMA DE GARANTÍA DE DEPÓSITOS EN EL SISTEMA FINANCIERO COSTARRICENSE

El objetivo principal de este documento consiste en evaluar el impacto que tendría sobre la exposición neta de los pasivos de los intermediarios financieros, el establecimiento de un sistema de seguro de depósitos tal como se encuentra propuesto en el Proyecto de Ley de Reformas de la Ley Orgánica del Banco Central de Costa Rica, la Ley Orgánica del Sistema Bancario Nacional y otras Leyes. Para tal efecto se recurre a la estimación de diferentes coberturas de pasivos y se realiza el análisis de diferentes escenarios.Los principales resultados indican que en el caso de los bancos estatales, contar con un fondo como el propuesto en el Proyecto analizado, permite reducir la exposición neta de los pasivos de un 40% a un 18% aproximadamente, lo cual significa que el aporte que deberá realizar el Gobierno se reduce considerablemente y con ello los costos que debe asumir la sociedad en términos de inflación ante un eventual problema financiero de un banco estatal.En cuanto a los bancos privados, existe diversidad en cuando a la capacidad de cubrir los pasivos, hay entidades que representan un mayor peso para el Fondo de Seguro de Depósitos propuesto, en tanto otras no presentan mayores problemas de cobertura.Por último debe destacarse que la metodología empleada constituye en si misma un aporte para ser considerada dentro de un sistema de indicadores de alerta temprana, puesto que muestra en forma indirecta el comportamiento de la calidad de activos y el apalancamiento.

Comportamento produtivo de cultivares de sorgo sacarino em Rio Branco-AC.

Visando avaliar a potencialidade da cultura, bem como estudar o comportamento produtivo de cultivares de sorgo na microrregião do Alto Purus, conduziu-se, no ano agrícola de 1983/84, na Fazenda Experimental da Embrapa, em Rio Branco, um experimento envolvendo quatro cultivares de sorgo procedentes do CNPMS, em Minas Gerais.

Perfil epidemiológico y análisis de la formulación antibiótica en pacientes con infección urinaria nosocomial en la Fundación Cardioinfantil en el año 2014

Introducción: La IVU es muy frecuenten en la (FCI - IC), Alrededor el 60% de los pacientes con diagnóstico de IVU nosocomial corresponden a gérmenes resistente, Desde el año 2010 el CLSI disminuyó los puntos de corte de sensibilidad en las enterobacteriaceae y removió la necesidad de tamizaje y confirmación de (BLEE), en el presente trabajo se pretende determinar el perfil epidemiológico de la formulación antibiótica en pacientes con IVU nosocomial. Diseño: Se realizó un estudio observacional analítico de corte transversal. Métodos: Se realizó un análisis univariado, bivariado y multivariado. El análisis bivariado y multivariado se realizó para determinar la medida de asociación teniendo en cuenta la formulación de Carbapenemico la variable dependiente, evaluándose mediante chi cuadrado. Resultados: Se revisaron 131 urocultivos, se incluyeron 116. Los aislamientos microbiológicos más frecuentemente encontrados fueron E. Coli y K. Pneumoniae, el 43.4% de los aislamientos, presentaron expresión de BLEE, 90% de los aislamientos fueron sensibles a Cefepime. La mayoría de los modelos obtenidos mostraron una fuerte asociación entre el reporte de BLEE en antibiograma con la formulación de carbapenémicos como terapia final OR 33,12 IC 95% (2,90 – 337,4). Conclusión: La epidemiologia de la IVU nosocomial en la FCI-IC no difiere de las referencias internacionales, no hay adherencia a las guías de manejo intrahospitalario y el reporte de la palabra BLEE en el antibiograma predice la formulación de antibiótico carbapenémico por el médico que lee el urocultivo

La exploración y producción de hidrocarburos en yacimientos no convencionales, frente a los principios de prevención, precaución y desarrollo sostenible

El presente trabajo de grado busca exponer el panorama actual de la exploración y producción de hidrocarburos en Yacimientos No Convencionales, realizada utilizando el fracturamiento hidráulico – Fracking – cómo método para lograr mejores condiciones físicas en el reservorio que permitan la extracción del recurso. El método mencionado es estudiado a la luz de los principios de prevención, precaución y desarrollo sostenible, que rigen la política ambiental en Colombia, con el objetivo de analizar los posibles impactos ambientales y sociales que se puedan generar por el desarrollo de la actividad extractiva de hidrocarburos en Yacimientos No Convencionales. Para finalmente mostrar que el Fracking como actividad está legalmente permitida en Colombia, y la legislación vigente responde a los principios mencionados previamente.