En busca del “N0”: siguiendo el camino de baldosas amarillas

In the last 15 years, the quantification of the reverse transcriptase chain reaction (RT-qPCR) has become the most widely used method for the quantification of gene expression (Baker M, Nature Methods, 2011, 8(3): 207-212). Some of its characteristics have contributed to the widespread use of this methodology: i) it is a one-step assay, without the need for post-PCR processing; ii) it allows a simple comparison between transcripts with a wide range of expression (differences 107 times); and iii) it uses the quantitative potential implicit in a conventional PCR, making it both a quantitative and qualitative assay.En los últimos 15 años, la cuantificación de la reacción en cadena de la transcriptasa inversa (RT-qPCR) se ha convertido en el método más utilizado para la cuantificación de la expresión génica (Baker M, Nature Methods, 2011, 8(3): 207-212). Algunos de sus características han contribuido al uso tan extendido de esta metodología: i) es un ensayo en un solo paso, sin la necesidad de proce- samiento post-PCR; ii) permite una comparación sencilla entre tránscritos con un rango amplio de expresión (diferencias  107 veces); y iii) utiliza el potencial cuantitativo implícito en una PCR convencional, haciéndolo un ensayo tanto cuantitativo como cualitativ

Extracardiac septum transversum/proepicardial endothelial cells pattern embryonic coronary arterio–venous connections

Recent reports suggest that mammalian embryonic coronary endothelium (CoE) originates from the sinus venosus and ventricular endocardium. However, the contribution of extracardiac cells to CoE is thought to be minor and nonsignificant for coronary formation. Using classic (Wt1(Cre)) and previously undescribed (G2-Gata4(Cre)) transgenic mouse models for the study of coronary vascular development, we show that extracardiac septum transversum/proepicardium (ST/PE)-derived endothelial cells are required for the formation of ventricular coronary arterio-venous vascular connections. Our results indicate that at least 20% of embryonic coronary arterial and capillary endothelial cells derive from the ST/PE compartment. Moreover, we show that conditional deletion of the ST/PE lineage-specific Wilms' tumor suppressor gene (Wt1) in the ST/PE of G2-Gata4(Cre) mice and in the endothelium of Tie2(Cre) mice disrupts embryonic coronary transmural patterning, leading to embryonic death. Taken together, our results demonstrate that ST/PE-derived endothelial cells contribute significantly to and are required for proper coronary vascular morphogenesi

Myocardial infarction ´through the window´: dual dynamics for cardiac fibroblasts activation

Activated cardiac fibroblasts (CFs) are responsible for the healing of the heart tissue after a myocardial infarction (MI). Based on high throughput technologies, several groups have recently demonstrated their heterogeneity and a unique role of each subpopulation of CFs during the ventricular remodelling process. This is relevant towards the discovery of personalized treatments to control the initial post-MI healing scar that will contribute to preserve ventricular function and prevent the onset of heart failure. However, little is known about the moment that CFs are activated, and which genes are potentially involved in this process. Using a mouse model for MI and single cell RNA-Seq, we demonstrate that the activation of Reparative Cardiac Fibroblasts (RCFs), the CFs responsible for the healing scar, happens within the first week after MI. Interestingly, our data reveals that all CFs show high expression of the top markers genes for RCF in a specific moment, but only few of them finally evolve to an RCF transcriptomic identity. Furthermore, we describe two different molecular dynamics that could give rise to this activation and, in consequence, the appearance of definitive RCFs. Using Spatial Transcriptomics, we localized the genes related to each dynamic in different anatomical regions of the infarcted heart, but, remarkably, only one persists seven days after MI. These results highlight the existence of a specific “window of activation” of RCFs at the beginning of the ventricular remodelling process. This potential ´therapeutical window´ could allow us to regulate the size of the healing scar and, in consequence, the poor prognosis for patients that have suffered an ischemic event.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

In vivo and In vitro cartilage differentiation from embryonic epicardial progenitor cells

The presence of cartilage tissue in embryonic and adult hearts of various vertebrate species is a well-recorded fact. However, while the embryonic neural crest has been historically considered as the main source of cardiac cartilage, recently reported results on the wide connective potential of epicardial lineage cells suggest they could also differentiate into chondrocytes. During heart embryogenesis, the epicardial epithelium forms over the originally bare myocardial surface from epicardial progenitor (proepicardial) cells to then give rise to a large population of mesenchymal Epicardial-Derived Cells (EPDCs) that will crucially contribute to the building, growth, and maturation of the ventricle and atrioventricular cardiac structures. In this work, we describe the formation of cardiac cartilage clusters from proepicardial cells, both in vivo and in vitro. Our findings report, for the first time, cartilage formation from epicardial progenitor cells in the embryonic heart, and strongly support the concept of proepicardial cells as multipotent connective progenitors. These results are relevant to our understanding of cardiac cell complexity and responses to pathologic stimuli.Universidad de Málaga (UMA18-FEDERJA-146). Campus de Excelencia Internacional Andalucía Tech; Ministerio de Educación (FPU18/05219); Ministerio de Ciencias (RTI2018-095410-B-I00); ISCIII-RETICs (RD16/0011/0030); Consejería de Salud y Familias, Junta de Andalucía (PIER-0084-2019) Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Las unidades del discurso oral. La propuesta Val.Es.Co. de segmentación de la conversación (coloquial)

El presente artículo resume y examina críticamente la propuesta de segmentación del discurso realizada en Briz y Grupo Val.Es.Co (2003). El modelo Val.Es.Co. consta de ocho unidades (discurso, diálogo, intercambio/ alternancia de turnos, intervención/turno, acto y subacto), tres órdenes (social, estructural e informativo) y cuatro posiciones (inicial, media, final e independiente); se caracteriza, además, por ser jerárquico y recursivo. La aplicación del modelo Val.Es.Co. permite la segmentación de una conversación coloquial sin residuos, así como un adecuado tratamiento de diversos fenómenos conversacionales (actos truncados, solapamientos, elementos suprasegmentales o marcadores discursivos)This paper summarizes and critically reviews the model of discourse segmentation made by Briz and Grupo Val.Es.Co (2003). This model is made up of eight units (discourse, dialogue, exchange/ turn taking, intervention/turn, act and subact), three orders (social, structural and informative) and four positions (initial, medial, final and independent). The Val.Es.Co model is also hyerarchical and recursive. By applying the Val.Es.Co model, a conversation can be divided into parts and subparts without any element remaining unanalyzed. Also, some specific features occurring in conversations such as false starts, overlappings, the segmentation value of prosodic features or discourse markers, can be successfully analyze

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

El Derecho del Trabajo y de la Seguridad Social en España en 2015. Sección Juvenil de la Asociación Española de Derecho del Trabajo y de la Seguridad Social.

Este Informe deja constancia de los cambios normativos más relevantes y de las tendencias judiciales más paradigmáticas del ordenamiento laboral en 2015. En él se observa el imparable dinamismo del Derecho del Trabajo y de la Seguridad Social en España. El documento, consciente de tal mutabilidad, recoge una minuciosa selección de cuestiones esenciales, a juicio de las personas que abordan cada una de las materias, de las que son especialistas; los autores y las autoras, que forman parte de la Sección Juvenil de la Asociación Española de Derecho del Trabajo y de la Seguridad Social, se adscriben a los grupos temáticos por afinidad con sus principales líneas de investigación y su labor docente universitaria. En síntesis, en el Informe “El Derecho del Trabajo y de la Seguridad Social en España en 2015” se puede encontrar información muy útil para los profesionales del iuslaboralismo en materia de derechos fundamentales inespecíficos, contratación laboral y empleo, vicisitudes del contrato de trabajo, derechos colectivos, igualdad y corresponsabilidad, Seguridad Social o prevención de riesgos laborales. This report has as aim leaving a record of the most relevant normative changes and the most paradigmatic judicial trends in Labour Law in 2015. One can easily observe the unstoppable dynamismof Labour and Social Security Law in Spain. The document, conscious of that mutability, collects a thorough selection of key issues, according to the judgement of the authors, all of them specialists and all of them members of the Young Scholars’ Section of the Spanish Association for Labour and Social Security Law. They are part of thematic groups, linked to their main research lines and their teaching task. Summing up, in this report “Labour and Social Security Law in Spain in 2015”, one can easily find useful information for labour lawyers in subjects such as unspecific fundamental rights, work contracts and employment, issues of the labour relationship, collective rights, equality and co-responsibility, Social Security or occupational risk prevention

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI