De la teoria de la causa y el fin o motivo determinante de la voluntad

uno de los temas mas interesantes y debatidos de la Teoria General de las Obligaciones, cual es, la Teoría de la Causa. Surge este elemento de carácter discutible que se llama "causa", en la formacion de las obligaciones y de los contratos: y adquiere carta de ciudadanía en el Derecho Francés para después pasar a otros derechos. Con motivo de este elemento, por demás polémico, se han elaborado dos teorías: una llamada causalista y otra anticausalista. En la teoría causalista encontramos diferentes etapas: 1o. La Doctrina Clásica de la Causa: 2o. La Doctrina Moderna de la Causa debida a Capitant y 3o. Las Doctrinas basadas en la jurisprudencia francesa de mediados del siglo pasado

An analysis of the spanish ceramic tile industry research contracts and patents

In this work, we apply a systemic approach to the analysis of a particular geographic territory, the industrial district. We are particularly interested in analysing the interaction between the productive-technological environment and the scientific environment by an examination of research contracts and patents. Our analysis shows that R&D activity in the Spanish ceramic tile District Innovation System was mainly conducted by suppliers. Final producers’ innovation efforts were related to non-technological aspects and differentiatio

Interventions for improving clinical outcomes and health-related quality-of-life for people living with skeletal dysplasias: an evidence gap map

Purpose: Skeletal dysplasias are rare genetic disorders that are characterized by abnormal development of bone and cartilage. There are multiple medical and non-medical treatments for specific symptoms of skeletal dysplasias e.g. pain, as well as corrective surgical procedures to improve physical functioning. The aim of this paper was to develop an evidence-gap map of treatment options for skeletal dysplasias, and their impact on patient outcomes. Methods: We conducted an evidence-gap map to identify the available evidence on the impact of treatment options on people with skeletal dysplasias on clinical outcomes (such as increase in height), and dimensions of health-related quality of life. A structured search strategy was applied to five databases. Two reviewers independently assessed articles for inclusion in two stages: titles and abstracts (stage 1), and full text of studies retained at stage 2. Results: 58 studies fulfilled our inclusion criteria. The included studies covered 12 types of skeletal dysplasia that are non-lethal with severe limb deformities that could result in significant pain and numerous orthopaedic interventions. Most studies reported on the effect of surgical interventions (n = 40, 69%), followed by the effect of treatments on dimensions of health quality-of-life (n = 4, 6.8%) and psychosocial functioning (n = 8, 13.8%). Conclusion: Most studies reported on clinical outcomes from surgery for people living with Achondroplasia. Consequently, there are gaps in the literature on the full range of treatment options (including no active treatment), outcomes and the lived experience of people living with other skeletal dysplasias. More research is warranted to examine the impact of treatments on health-related quality-of-life of people living with skeletal dysplasias, including their relatives to enable them to make preference- and valued based decisions about treatment

Highly trabeculated structure of the human endocardium underlies asymmetrical response to low-energy monophasic shocks

Novel low-energy defibrillation therapies are thought to be driven by virtual-electrodes (VEs), due to the interaction of applied monophasic electric shocks with fine-scale anatomical structures within the heart. Significant inter-species differences in the cardiac (micro)-anatomy exist, however, particularly with respect to the degree of endocardial trabeculations, which may underlie important differences in response to low-energy defibrillation protocols. Understanding the interaction of monophasic electric fields with the specific human micro-anatomy is therefore imperative in facilitating the translation and optimisation of these promising experimental therapies to the clinic. In this study, we sought to investigate how electric fields from implanted devices interact with the highly trabeculated human endocardial surface to better understand shock success in order to help optimise future clinical protocols. A bi-ventricular human computational model was constructed from high resolution (350 μm) ex-vivo MR data, including anatomically accurate endocardial structures. Monophasic shocks were applied between a basal right ventricular catheter and an exterior ground. Shocks of varying strengths were applied with both anodal [positive right ventricle (RV) electrode] and cathodal (negative RV electrode) polarities at different states of tissue refractoriness and during induced arrhythmias. Anodal shocks induced isolated positive VEs at the distal side of “detached” trabeculations, which rapidly spread into hyperpolarised tissue on the surrounding endocardial surfaces following the shock. Anodal shocks thus depolarised more tissue 10 ms after the shock than cathodal shocks where the propagation of activation from VEs induced on the proximal side of “detached” trabeculations was prevented due to refractory endocardium. Anodal shocks increased arrhythmia complexity more than cathodal shocks during failed anti-arrhythmia shocks. In conclusion, multiple detached trabeculations in the human ventricle interact with anodal stimuli to induce multiple secondary sources from VEs, facilitating more rapid shock-induced ventricular excitation compared to cathodal shocks. Such a mechanism may help explain inter-species differences in response to shocks and help to develop novel defibrillation strategies

Determinación de Mercurio, Cadmio, Plomo y Arsénico en ríos de la zona minera de la subcuenca del Río Titihuapa, Cabañas, El Salvador

La subcuenca del río Titihuapa en el departamento de Cabañas alberga parte del vulcanismo Terciario de El Salvador en esa región, y por ende posee una abundancia de minerales. La actividad minera que se desarrolló desde finales del siglo XIX, hizo figurar a esta zona como una de las más propicias para la explotación de oro y plata en El Salvador. Sin embargo, esta prosperidad minera, pudo haber propiciado la contaminación metálica de buena parte de la cuenca del río Titihuapa. La metodología empleada incluyó la toma de muestras de sedimentos en sitios ubicados en los puntos de confluencia de los ríos tributarios a la subcuenca Titihuapa, las cuales fueron resguardadas y transportadas al laboratorio para su respectivo análisis mediante técnicas de absorción atómica, método de horno de grafito y método de generador de flama. Se usó como parámetro el nivel de efectos leves (NEL) de la Guía Para la Evaluación de Sedimentos, del departamento de Protección Ambiental de New Jersey, 1998. Las concentraciones de Hg, Cd y Pb están por debajo de los valores de la NEL. Las concentraciones de As, la mayoría sobrepasa el NEL que es de 6.0 µg/g

Small molecules containing chalcogen elements (S, Se, Te) as new warhead to fight neglected tropical diseases

Neglected tropical diseases (NTDs) encompass a group of infectious diseases with a protozoan etiology, high incidence, and prevalence in developing countries. As a result, economic factors constitute one of the main obstacles to their management. Endemic countries have high levels of poverty, deprivation and marginalization which affect patients and limit their access to proper medical care. As a matter of fact, statistics remain un- collected in some affected areas due to non-reporting cases. World Health Organization and other organizations proposed a plan for the eradication and control of the vector, although many of these plans were halted by the COVID-19 pandemic. Despite of the available drugs to treat these pathologies, it exists a lack of effectiveness against several parasite strains. Treatment protocols for diseases such as American trypanosomiasis (Chagas disease), leishmaniasis, and human African trypanosomiasis (HAT) have not achieved the desired results. Un- fortunately, these drugs present limitations such as side effects, toxicity, teratogenicity, renal, and hepatic impairment, as well as high costs that have hindered the control and eradication of these diseases. This review focuses on the analysis of a collection of scientific shreds of evidence with the aim of identifying novel chalcogen- derived molecules with biological activity against Chagas disease, leishmaniasis and HAT. Compounds illustrated in each figure share the distinction of containing at least one chalcogen element. Sulfur (S), selenium (Se), and tellurium (Te) have been grouped and analyzed in accordance with their design strategy, chemical synthesis process and biological activity. After an exhaustive revision of the related literature on S, Se, and Te compounds, 183 compounds presenting excellent biological performance were gathered against the different causative agents of CD, leishmaniasis and HAT

Biallelic JAK1 mutations in immunodeficient patient with mycobacterial infection

Mutations in genes encoding components of the immune system cause primary immunodeficiencies. Here, we study a patient with recurrent atypical mycobacterial infection and early-onset metastatic bladder carcinoma. Exome sequencing identified two homozygous missense germline mutations, P733L and P832S, in the JAK1 protein that mediates signalling from multiple cytokine receptors. Cells from this patient exhibit reduced JAK1 and STAT phosphorylation following cytokine stimulations, reduced induction of expression of interferon-regulated genes and dysregulated cytokine production; which are indicative of signalling defects in multiple immune response pathways including Interferon-γ production. Reconstitution experiments in the JAK1-deficient cells demonstrate that the impaired JAK1 function is mainly attributable to the effect of the P733L mutation. Further analyses of the mutant protein reveal a phosphorylation-independent role of JAK1 in signal transduction. These findings clarify JAK1 signalling mechanisms and demonstrate a critical function of JAK1 in protection against mycobacterial infection and possibly the immunological surveillance of cancer.Wellcome Trust (095198/Z/10/Z and 090233/Z/09/Z); Higher Education Funding Council for England; Great Ormond Street Hospital Children’s Charity; National Institute for Health Research (NIHR); Great Ormond Street Hospital Biomedical Research Centre; NIHR Cambridge Biomedical Research Centre; Alfonso Martin Escudero Foundatio

Systemic metabolic derangement, pulmonary effects, and insulin insufficiency following subchronic ozone exposure in rats

Acute ozone exposure induces a classical stress response with elevated circulating stress hormones along with changes in glucose, protein and lipid metabolism in rats, with similar alterations in ozone-exposed humans. These stress-mediated changes over time have been linked to insulin resistance. We hypothesized that acute ozone-induced stress response and metabolic impairment would persist during subchronic episodic exposure and induce peripheral insulin resistance. Male Wistar Kyoto rats were exposed to air or 0.25 ppm or 1.00 ppm ozone, 5 h/day, 3 consecutive days/week (wk) for 13 wks. Pulmonary, metabolic, insulin signaling and stress endpoints were determined immediately after 13 wk or following a 1 wk recovery period (13 wk + 1 wk recovery). We show that episodic ozone exposure is associated with persistent pulmonary injury and inflammation, fasting hyperglycemia, glucose intolerance, as well as, elevated circulating adrenaline and cholesterol when measured at 13 wk, however, these responses were largely reversible following a 1 wk recovery. Moreover, the increases noted acutely after ozone exposure in non-esterified fatty acids and branched chain amino acid levels were not apparent following a subchronic exposure. Neither peripheral or tissue specific insulin resistance nor increased hepatic gluconeogenesis were present after subchronic ozone exposure. Instead, long-term ozone exposure lowered circulating insulin and severely impaired glucose-stimulated beta-cell insulin secretion. Thus, our findings in young-adult rats provide potential insights into epidemiological studies that show a positive association between ozone exposures and type 1 diabetes. Ozone-induced beta-cell dysfunction may secondarily contribute to other tissue-specific metabolic alterations following chronic exposure due to impaired regulation of glucose, lipid, and protein metabolism

Evidences of volcanic unrest on high-temperature fumaroles by satellite thermal monitoring: The case of Santa Ana volcano, El Salvador

International audienceOn October 1st, 2005, Santa Ana volcano (El Salvador) underwent a VEI 3 phreatomagmatic eruption after approximately one century of rest. Casualties and damages to some of the local infrastructures and surrounding plantations were followed by the evacuation of the nearby communities. The analysis of MODIS (Moderate Resolution Imaging Spectroradiometer) infrared data reveals that the main explosion was preceded by a one-year-long thermal unrest, associated to the development of a fumaroles field, located at the western rim of the summit crater lake. By combining space-based thermal flux and ground-based measurements (seismicity, sulfur emissions and lake temperatures), we suggest that the activity observed at Santa Ana between 2004 and 2005 was driven by the gradual intrusion of an undegassed magma body at a very shallow depth. Magma injection induced thermal anomalies associated with sustained degassing from the fumaroles field and promoted the interaction between the magmatic-hydrothermal system and the overlying water table. This process culminated into the VEI 3 phreatomagmatic eruption of October 2005 that strongly modified the shallow structure of the crater area. The subsequent three-years-long activity resulted from self-sealing of the fracture system and by the opening of a new fracture network directly connecting the deeper hydrothermal system with the crater lake. Our results show that satellite-based thermal data allow us to detect the expansion of the high-temperature fumarolic field. This may precede an explosive eruption and/or a lava dome extrusion. In particular, we show that thermal records can be analyzed with other geochemical (i.e. SO2 emissions) and geophysical (seismicity) data to track a shallow magmatic intrusion interacting with the surrounding hydrothermal system. This provides a remarkable support for volcano monitoring and eruption forecasting, particularly in remote areas where permanent ground data acquisition is hazardous, expensive and difficult