58 research outputs found

    Sedimentology and sedimentary evolution of the Artoles Fm in Miravete de la Sierra (Teruel, Iberian Chain)

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    The sedimentology and sedimentary evolution of the Barremian Artoles Fm in the Camino de Miravete section (Galve sub-basin, Spain) is presented. The detailed log of the stratigraphic succession together with facies analysis and fossil content have allowed the distinction of four main facies associations: mixed terrigenous-carbonate lagoon, flood-tidal delta, proximal middle ramp and distal middle ramp. The sedimentary evolution of facies associations characterizes three successive stages: I- restricted carbonate lagoon system, II- middle ramp system and III- turning back to another carbonate lagoon with more open facies. Eustasy and tectonics may be responsible of the abrupt deepening that took place between stages I and II

    Nottingham Prognostic Index Plus (NPI+): a modern clinical decision making tool in breast cancer

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    Current management of breast cancer (BC) relies on risk stratification based on well-defined clinicopathologic factors. Global gene expression profiling studies have demonstrated that BC comprises distinct molecular classes with clinical relevance. In this study, we hypothesized that molecular features of BC are a key driver of tumour behaviour and when coupled with a novel and bespoke application of established clinicopathologic prognostic variables, can predict both clinical outcome and relevant therapeutic options more accurately than existing methods. In the current study, a comprehensive panel of biomarkers with relevance to BC was applied to a large and well-characterised series of BC, using immunohistochemistry and different multivariate clustering techniques, to identify the key molecular classes. Subsequently, each class was further stratified using a set of well-defined prognostic clinicopathologic variables. These variables were combined in formulae to prognostically stratify different molecular classes, collectively known as the Nottingham Prognostic Index Plus (NPI+). NPI+ was then used to predict outcome in the different molecular classes with.Seven core molecular classes were identified using a selective panel of 10 biomarkers. Incorporation of clinicopathologic variables in a second stage analysis resulted in identification of distinct prognostic groups within each molecular class (NPI+). Outcome analysis showed that using the bespoke NPI formulae for each biological breast cancer class provides improved patient outcome stratification superior to the traditional NPI. This study provides proof-of-principle evidence for the use of NPI+ in supporting improved individualised clinical decision making

    Combining clustering and classification ensembles: A novel pipeline to identify breast cancer profiles

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    Breast Cancer is one of the most common causes of cancer death in women, representing a very complex disease with varied molecular alterations. To assist breast cancer prognosis, the classification of patients into biological groups is of great significance for treatment strategies. Recent studies have used an ensemble of multiple clustering algorithms to elucidate the most characteristic biological groups of breast cancer. However, the combination of various clustering methods resulted in a number of patients remaining unclustered. Therefore, a framework still needs to be developed which can assign as many unclustered (i.e. biologically diverse) patients to one of the identified groups in order to improve classification. Therefore, in this paper we develop a novel classification framework which introduces a new ensemble classification stage after the ensemble clustering stage to target the unclustered patients. Thus, a step-by-step pipeline is introduced which couples ensemble clustering with ensemble classification for the identification of core groups, data distribution in them and improvement in final classification results by targeting the unclustered data. The proposed pipeline is employed on a novel real world breast cancer dataset and subsequently its robustness and stability are examined by testing it on standard datasets. The results show that by using the presented framework, an improved classification is obtained. Finally, the results have been verified using statistical tests, visualisation techniques, cluster quality assessment and interpretation from clinical experts

    The combined expression of solute carriers is associated with a poor prognosis in highly proliferative ER+ breast cancer

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    Purpose: Breast cancer (BC) is a heterogeneous disease characterised by variant biology, metabolic activity, and patient outcome. Glutamine availability for growth and progression of BC is important in several BC subtypes. This study aimed to evaluate the biological and prognostic role of the combined expression of key glutamine transporters, SLC1A5, SLC7A5 and SLC3A2 in BC with emphasis on the intrinsic molecular subtypes. Methods: SLC1A5, SLC7A5 and SLC3A2 were assessed at the protein level, using immunohistochemistry on tissue microarrays constructed from a large well characterised BC cohort (n=2,248). Patients were stratified into accredited clusters based on protein expression and correlated with clinicopathological parameters, molecular subtypes, and patient outcome. Results: Clustering analysis of SLC1A5, SLC7A5 and SLC3A2 identified three clusters Low SLCs (SLC1A5-/SLC7A5-/SLC3A2-), High SLC1A5 (SLC1A5+/SLC7A5-/SLC3A2-) and High SLCs (SLC1A5+/SLC7A5+/SLC3A2+) which had distinct correlations to known prognostic factors and patient outcome (p<0.001). The key regulator of tumour cell metabolism, c-MYC, was significantly expressed in tumours in the High SLCs cluster (p<0.001). When different BC subtypes were considered, the association with the poor outcome was observed in the ER+ high proliferation/luminal B class only (p= 0.003). In multivariate analysis, SLC clusters were independent risk factor for shorter breast cancer specific survival (p= 0.001). Conclusion: The co-operative expression of SLC1A5, SLC7A5 and SLC3A2 appears to play a role in the aggressive subclass of ER+ high proliferation/ luminal BC, driven by c-MYC, and therefore have the potential to act as therapeutic targets, particularly in synergism

    Resolviendo un asesinato: una experiencia con la Geología Forense como estrategia de enseñanza-aprendizaje en la Educación Secundaria

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    El trabajo se inspira en la Geología Forense como estrategia de enseñanza-aprendizaje de la Geología para ESO y Bachillerato. Se pretende proveer al profesorado de un recurso u´til y estructurado, complementario para su tarea didáctica. Los objetivos generales se resumen en: 1) Fomentar la motivación hacia la Geología mostrándola como una ciencia capaz de resolver problemas que interesen al alumnado, en este caso por su similitud con series policiacas. 2) Incrementar la creatividad y el trabajo cooperativo de los estudiantes y su interés por el aprendizaje de la ciencia básica y sus métodos. El proyecto está centrado en el alumnado y aporta una metodología basada en la enseñanza de las ciencias centrada en la indagación. Además, persigue la adquisición de la competencia “interpretar datos y pruebas científicamente”, buscando indicios o evidencias mediante dinámicas de gamificación, todo ello aplicable a otros campos de la ciencia. Para ello se utilizan un conjunto de destrezas como la observación de muestras geológicas a diferentes escalas (visu y microscopía) y el manejo de la bru´jula. Es un modelo de experiencia sencillo de realizar, precisa de materiales de bajo coste, que se puede adaptar y aplicar en diferentes contextos académicos, cientí cos y sociales. Las características mencionadas han hecho a esta experiencia merecedora del Primer Premio del concurso “Ciencia en Acción” 2017 en la modalidad Laboratorio de Geología. La actividad se ha realizado, durante este curso académico, en diferentes centros de secundaria aragoneses, lo que permite recomendar el repaso de algunos contenidos previamente a su desarrollo en el aula. The project is inspired by Forensic Geology as a Geology teaching and learning strategy for students of Secondary School in Spain (E.S.O. and Bachillerato). It provides teachers in charge of these levels with a useful and well-structured resource as a complementary tool for their didactic tasks. The main objectives are: 1) Motivating students towards Geology by presenting it as a science able to give answers to problems students are interested in, in this case for its similarity with crime series. 2) Increasing students’ creativity and cooperative work and their interest in learning basic Science and its methods. We present a student-centred project; its methodology is based on Earth Sciences teaching, mainly focused on inquiry. One of the main objectives of the proposed activity is the acquisition of the skill “scienti c interpretation of data and evidence“ by searching for clues and evidence through gami cation dynamics, all of which is applicable to other elds of Science. For these purposes skills such as the study of geological samples at different scales, or orientation and compass navigation are put to use. This experience is easy to put into practice, the materials needed are affordable and present in any school. It can be adapted to different scienti c, social and academic contexts. By virtue of the above- mentioned characteristics this contribution deserved the First Prize in the Spanish state competition “Ciencia en Accio´n 2017” (Science in Action) in the Geology Lab section. This activity has been carried out, during this academic year, in different secondary schools in Aragon so we can recommend a revision of some contents prior to their implementation in the classroom

    Cicloestratigrafía del Grupo Enciso, Cuenca oriental de Cameros (N de España)

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    El Grupo Enciso (Cretácico Inferior) se localiza en la parte oriental de la Cuenca de Cameros. Está formado por arenis- cas, limolitas, margas y calizas organizadas en ciclos de diferente rango que han sido interpretados como de origen orbital (Angulo y Muñoz, 2013; Hernán, 2018; Muñoz et al., en prensa). En los alrededores de Navalsaz (La Rioja) se ha levantado un perfil estratigráfico de 1.371 m donde se han medido valores de susceptibilidad magnética cada 50 cm y se han tomado muestras cada metro para la medida en laboratorio del contenido en carbonato y de parámetros de color (CIE L*a*b*). Se han construido series de tiempo continuas cuantitativas de la susceptibilidad magnética, el contenido total de carbonato, la luminosidad (L*), y las coordenadas rojo/verde (a*) y amarillo/azul (b*). El análisis espectral de estas series de tiempo ha puesto de manifiesto la existencia de ciclos referibles a las frecuencias de Milankovitch de excentricidad, oblicuidad y precesión. The Enciso Group (Lower Cretaceous) is located in the eastern part of Cameros Basin. It is made up of sandstones, limolites, marls and limestones organized in different rank cycles which have been interpreted as orbitally-controlled cycles (Angulo and Muñoz, 2013; Hernán, 2018; Muñoz et al., in press). Magnetic susceptibility was measured every 50 cm in a 1,371 m-thick stratigraphic column made nearby of Navalsaz (La Rioja), and samples, spaced every meter, taken for carbonate content and colour parameter measurements (CIE L* a* b*) in the laboratory. Continuous quantitative time series were built based on magnetic susceptibility values, total carbonate content, luminosity (L*), as well as red/green (a*) and yellow/blue (b*) coordinates. The spectral analysis of such series reveals the existence of cycles that can be referred to eccentricity, obliquity and precession Milankovitch frequencies

    'Disc-jet' coupling in black hole X-ray binaries and active galactic nuclei

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    In this chapter I will review the status of our phenomenological understanding of the relation between accretion and outflows in accreting black hole systems. This understanding arises primarily from observing the relation between X-ray and longer wavelength (infrared, radio) emission. The view is necessarily a biased one, beginning with observations of X-ray binary systems, and attempting to see if they match with the general observational properties of active galactic nuclei.Comment: 28 pages, 15 figures, To appear in Belloni, T. (ed.): The Jet Paradigm - From Microquasars to Quasars, Lect. Notes Phys. 794 (2009
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