Tumour genomic and microenvironmental heterogeneity for integrated prediction of 5-year biochemical recurrence of prostate cancer: a retrospective cohort study.

BACKGROUND Clinical prognostic groupings for localised prostate cancers are imprecise, with 30-50% of patients recurring after image-guided radiotherapy or radical prostatectomy. We aimed to test combined genomic and microenvironmental indices in prostate cancer to improve risk stratification and complement clinical prognostic factors. METHODS We used DNA-based indices alone or in combination with intra-prostatic hypoxia measurements to develop four prognostic indices in 126 low-risk to intermediate-risk patients (Toronto cohort) who will receive image-guided radiotherapy. We validated these indices in two independent cohorts of 154 (Memorial Sloan Kettering Cancer Center cohort [MSKCC] cohort) and 117 (Cambridge cohort) radical prostatectomy specimens from low-risk to high-risk patients. We applied unsupervised and supervised machine learning techniques to the copy-number profiles of 126 pre-image-guided radiotherapy diagnostic biopsies to develop prognostic signatures. Our primary endpoint was the development of a set of prognostic measures capable of stratifying patients for risk of biochemical relapse 5 years after primary treatment. FINDINGS Biochemical relapse was associated with indices of tumour hypoxia, genomic instability, and genomic subtypes based on multivariate analyses. We identified four genomic subtypes for prostate cancer, which had different 5-year biochemical relapse-free survival. Genomic instability is prognostic for relapse in both image-guided radiotherapy (multivariate analysis hazard ratio [HR] 4·5 [95% CI 2·1-9·8]; p=0·00013; area under the receiver operator curve [AUC] 0·70 [95% CI 0·65-0·76]) and radical prostatectomy (4·0 [1·6-9·7]; p=0·0024; AUC 0·57 [0·52-0·61]) patients with prostate cancer, and its effect is magnified by intratumoral hypoxia (3·8 [1·2-12]; p=0·019; AUC 0·67 [0·61-0·73]). A novel 100-loci DNA signature accurately classified treatment outcome in the MSKCC low-risk to intermediate-risk cohort (multivariate analysis HR 6·1 [95% CI 2·0-19]; p=0·0015; AUC 0·74 [95% CI 0·65-0·83]). In the independent MSKCC and Cambridge cohorts, this signature identified low-risk to high-risk patients who were most likely to fail treatment within 18 months (combined cohorts multivariate analysis HR 2·9 [95% CI 1·4-6·0]; p=0·0039; AUC 0·68 [95% CI 0·63-0·73]), and was better at predicting biochemical relapse than 23 previously published RNA signatures. INTERPRETATION This is the first study of cancer outcome to integrate DNA-based and microenvironment-based failure indices to predict patient outcome. Patients exhibiting these aggressive features after biopsy should be entered into treatment intensification trials. FUNDING Movember Foundation, Prostate Cancer Canada, Ontario Institute for Cancer Research, Canadian Institute for Health Research, NIHR Cambridge Biomedical Research Centre, The University of Cambridge, Cancer Research UK, Cambridge Cancer Charity, Prostate Cancer UK, Hutchison Whampoa Limited, Terry Fox Research Institute, Princess Margaret Cancer Centre Foundation, PMH-Radiation Medicine Program Academic Enrichment Fund, Motorcycle Ride for Dad (Durham), Canadian Cancer Society.

Conservation of the Cinereous Vulture Aegypius monachus in Spain (1966–2011): a bibliometric review of threats, research and adaptive management

Detecting and quantifying threats and researching and implementing management actions are key to improving the conservation status of endangered species. Bibliometric analysis can constitute a useful tool for the evaluation of such questions from a long-term perspective. Taking as a case study the Cinereous Vulture Aegypius monachus in Spain, we tested relationships between population dynamics, research efforts, existing threats and conservation milestones. The population growth of the species (from 206 pairs in 1976 to 2,068 in 2011) was parallelled by the increase in the total number of publications, the number of articles in SCI journals and the number of published works dealing with aspects of conservation, threats and management. These results are discussed in terms of cause-effect relationships taking into account that the influence of other non-mutually exclusive factors could also probably explain such associations. Similarly, we analysed the trend of the Cinereous Vulture breeding population with respect to different threats and indices of food availability, obtaining a positive correlation with the increase in big-game hunting bags in Spain. With respect to conservation milestones, we concluded that the current situation is positive in terms of the protection of the species and its habitat, with the situation in relation to food availability being unclear. Finally, we reviewed the main conservation actions that have been taken for the species in Spain and how these have been progressively modified based on new scientific and technical evidence, as an example of adaptive management applied to conservation.

Measurement of the production of a W boson in association with a charm quark in pp collisions at sqrts = 7 TeV with the ATLAS detector

The production of a W boson in association with a single charm quark is studied using 4.6 fb−1 of pp collision data at ps = 7TeV collected with the ATLAS detector at the Large Hadron Collider. In events in which a W boson decays to an electron or muon, the charm quark is tagged either by its semileptonic decay to a muon or by the presence of a charmed meson. The integrated and differential cross sections as a function of the pseudorapidity of the lepton from the W-boson decay are measured. Results are compared to the predictions of next-to-leading-order QCD calculations obtained from various parton distribution function parameterisations. The ratio of the strange-to-down sea-quark distributions is determined to be 0.96+0.26−0.30 at Q2 = 1.9 GeV2, which supports the hypothesis of an SU(3)-symmetric composition of the light-quark sea. Additionally, the cross-section ratio ơ(W++c)/ơ(W−+c) is compared to the predictions obtained using parton distribution function parameterisations with different assumptions about the s–s quark asymmetry.

Similar outcome of upfront-unrelated and matched sibling stem cell transplantation in idiopathic paediatric aplastic anaemia. A study on behalf of the UK Paediatric BMT Working Party, Paediatric Diseases Working Party and Severe Aplastic Anaemia Working Party of EBMT

Abstract We explored the feasibility of unrelated donor haematopoietic stem cell transplant (HSCT) upfront without prior immunosuppressive therapy (IST) in paediatric idiopathic severe aplastic anaemia (SAA). This cohort was then compared to matched historical controls who had undergone first-line therapy with a matched sibling/family donor (MSD) HSCT (n = 87) or IST with horse antithymocyte globulin and ciclosporin (n = 58) or second-line therapy with unrelated donor HSCT post-failed IST (n = 24). The 2-year overall survival in the upfront cohort was 96 ± 4% compared to 91 ± 3% in the MSD controls (P = 0·30) and 94 ± 3% in the IST controls (P = 0·68) and 74 ± 9% in the unrelated donor HSCT post-IST failure controls (P = 0·02).The 2-year event-free survival in the upfront cohort was 92 ± 5% compared to 87 ± 4% in MSD controls (P = 0·37), 40 ± 7% in IST controls (P = 0·0001) and 74 ± 9% in the unrelated donor HSCT post-IST failure controls (n = 24) (P = 0·02). Outcomes for upfront-unrelated donor HSCT in paediatric idiopathic SAA were similar to MSD HSCT and superior to IST and unrelated donor HSCT post-IST failure. Front-line therapy with matched unrelated donor HSCT is a novel treatment approach and could be considered as first-line therapy in selected paediatric patients who lack a MSD. © 2015 John Wiley & Sons Ltd.

Escuelas bilingues de frontera: discursos (des) encontrados. 16H225

El proyecto tiene como propósito analizar los discursos de docentes y funcionarios argentinos y brasileños que integran el Programa bilateral de Enseñanza Común para Escuelas de Frontera Español-portugués. El interés por la temática reside en desvendar problemas existentes en el programa. Problemas que creemos que en parte se fundan en las diferencias conceptuales e ideológicas que se vislumbran al comparar los discursos de los participantes argentinos y brasileños. Para realizar la investigación se seleccionó un corpus de textos basados en diferentes trabajos de campo, tales como: entrevistas, observaciones de clases, notas, textos de circulación interna del programa (acuerdos, informes, relatorías, grabaciones de reuniones, planificaciones conjuntas, etc.). El análisis del mismo fue abordado desde la perspectiva del análisis del discurso.) Objetivos del Proyecto -Identificar cuáles son los conceptos que subyacen en los discursos políticos pedagógicos de equipos técnicos y docentes de ambos países. -Reconocer los factores discursivo-culturales que provocan confusiones y malos entendidos entre argentinos y brasileños. -Interpretar los efectos de sentidos producidos en la interdiscursividad del programa. -Estudiar la problemática para contribuir a mejorar las re

Lengua indígena: lengua extranjera en tierra indígena. En: Avá, nº 14

A pesar de las reiteradas manifestaciones y instrucciones al respecto del valor de las lenguas indígenas y sobre la importancia de la enseñanza en lengua materna, sea en documentos oficiales del gobierno brasileño, sea en artículos, declaraciones y propuestas firmadas por maestros indígenas o por pesquisadores no indígenas, el hecho es que en la mayor parte de los programas educacionales en comunidades indígenas de Brasil el espacio destinado a la lengua autóctona es muy semejante a lo que acostumbramos encontrar para una lengua extranjera en la escuela nacional. Como a menudo los maestros indígenas demuestran tener convicción en la necesidad de valorizar y fortalecer sus lenguas propias, y son – ellos mismos – hablantes nativos de sus lenguas, las preguntas que se plantean son: ¿Por cuales razones las escuelas indígenas siguen restringiendo el espacio de la lengua autóctona? ¿Es posible que los maestros indígenas de hecho estén creyentes de las potencialidades y en el futuro de su lengua materna? Y, por fin, ¿Serán las presiones de la burocracia o de maestros no-indígenas en la escuela indígena lo que impide la experimentación de programas auténticamente bilingües?

Aportes semióticos para la alfabetización en umbrales. 16H246

Actividades desarrolladas durante el período: Marco teórico: organización del corpus conceptual y de categorías teóricas; trabajo de campo: en esta etapa, se terminaron de definir las unidades de observación para una descripción in situ de las prácticas alfabetizadoras rurales, afianzando trabajos con la “red de escuelas rurales” de la localidad de San Javier (en la costa del río Uruguay); por otra parte, para la construcción del perfil alfabetizador del umbral, se realizaron reuniones de trabajo y conversaciones con docentes de los IFDC de zonas rurales; avances en la escritura de la tesis en una organización de cuyo contenido da cuenta el índice que se adjunta; redacción de avances, logros de proceso, síntesis parciales en la escritura de ensayos, ponencias, artículos que se mencionan en el ítem siguiente de este informe; asistencia a Congresos y jornadas con presentación de ponencias e intercambios con pares de la comunidad científica; cursado del último semestre del posgrado doctoral: asistencia a seminarios y al último taller de tesis (actividad de cierre del bloque de investigación del doctorado) con presentación y exposición de avances, logros y obstáculos en el proceso investigativo que han sido evaluados y aprobados sin objeción por el comité académico.