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Innovative cross-over study designs were explored in non-human primate (NHP) studies to determine the value of this approach for the evaluation of drug efficacy against tuberculosis (TB). Firstly, the pharmacokinetics (PK) of each of the drugs Isoniazid (H), Rifampicin (R), Pyrazinamide (Z) and Ethambutol (E), that are standardly used for the treatment of tuberculosis, was established in the blood of macaques after oral dosing as a monotherapy or in combination. Two studies were conducted to evaluate the pharmacokinetics and pharmacodynamics of different drug combinations using cross-over designs. The first employed a balanced, three-period Pigeon design with an extra period; this ensured that treatment by period interactions and carry-over could be detected comparing the treatments HR, HZ and HRZ using H37Rv as the challenge strain of Mycobacterium tuberculosis (M. tb). Although the design accounted for considerable variability between animals, the three regimens evaluated could not be distinguished using any of the alternative endpoints assessed. However, the degree of pathology achieved using H37Rv in the model during this study was less than expected. Based on these findings, a second experiment using a classical AB/BA design comparing HE with HRZ was conducted using the M. tb Erdman strain. More extensive pathology was observed, and differences in computerized tomography (CT) scores and bacteriology counts in the lungs were detected, although due to the small group sizes, clearer differences were not distinguished. Type 1 T helper (Th1) cell response profiles were characterized using the IFN-γ ELISPOT assay and revealed differences between drug treatments that corresponded to decreases in disease burden. Therefore, the studies performed support the utility of the NHP model for the determination of PK/PD of TB drugs, although further work is required to optimize the use of cross-over study designs.

Los problemas de localización tratan de averiguar la ubicación de las instalaciones de una empresa de modo que se minimicen los costes o se maximicen los beneficios. Dos de los modelos más utilizados en localización en redes son el problema de la p-mediana y el problema del p-centro. El primero consiste en minimizar la suma total de las distancias ponderadas, mientras que el segundo trata de minimizar la máxima distancia ponderada desde un centro de servicio hasta sus usuarios asignados. El objetivo del problema de la p-mediana hace que sea eficiente pero no equitativo, mientras que la cota implícita en el problema del p-centro lo convierte en equitativo pero no eficiente. Para combinar ambos aspectos, aparece en la década de los 70 un nuevo problema, el de la p-centdiana, cuya función objetivo es una mezcla de las dos anteriores. En este trabajo presentamos un modelo de programación binaria mixta para el problema generalizado de la p-centdiana sobre una red en el que los pesos asociados al p-centro y a la p-mediana no son necesariamente iguales. El primer paso para resolver el problema es identificar su conjunto dominante finito. En consecuencia, previamente a la descripción del modelo, proponemos un algoritmo que nos permitirá calcular este conjunto.

El problema de la p-mediana es un modelo básico de localización en redes donde las longitudes de las aristas (distancias) y los pesos de los vértices (demandas) son conocidos. Consiste en encontrar p puntos de la red de modo que se minimice la distancia total ponderada entre estos puntos y los vértices. Como la mayoría de problemas de localización, se utiliza para tomar decisiones a largo plazo en un entorno incierto. En consecuencia, la hipótesis de que los datos son deterministas no parece apropiada para resolver un problema real. En este trabajo presentamos el problema de la mediana sobre un árbol con incertidumbre en las demandas, resuelto mediante técnicas de optimización robusta. En concreto, hemos supuesto que la incertidumbre viene reflejada por el hecho de que cada demanda puede variar en un rango de valores. Nuestro objetivo es conseguir una solución que, cuando los datos tomen algún valor en el futuro, minimice la demanda no atendida y cuyo coste no esté muy lejos del mínimo coste que hubiésemos obtenido de saber con antelación el auténtico valor de los datos. Puesto que la forma de plantear matemáticamente este objetivo no es única, presentamos y comparamos varias opciones entre las que puede elegir el decisor.

Abstract Background The identification of patients with advanced chronic conditions and palliative care needs is essential since their care represents one of the main challenges for public health systems. The study aimed to determine the prevalence and characteristics of inpatients with palliative care needs in different services of a tertiary care hospital using the NECPAL CCOMS-ICO© tool. Methods A descriptive, cross-sectional cohort study was conducted in a tertiary hospital. The NECPAL tool identifies patients who require palliative care. Any patient with the Surprise Question with the answer “NO” and at least another question of the tool with a positive answer is considered a positive identification. Patients were classified as Non-NECPAL, NECPAL I-II, and NECPAL III, depending on the NECPAL tool criteria they met. The presence of physical symptoms, emotional distress, and social risk factors was assessed. Results Of the 602 inpatients, 236 (39.2%) were enrolled. Of them, 34 (14.4%) non-NECPAL, 202 (85.6%) NECPAL+ [105 (44.5%) NECPAL I-II, and 97 (41.1%) NECPAL III]. Physical symptom burden was high (pain intensity ≥ 1 in 68.3% of patients; tiredness ≥ 1 in 83.5%; somnolence ≥ 1 in 50.6%; dyspnea ≥ 1 in 37.9%; anorexia ≥ 1 in 59.5%). 64.1% had emotional distress, and 83.6% had social risk factors. The NECPAL-III group contained a higher percentage of cancer patients, higher demand for palliative care, and greater need for palliative care (p

¿Cómo hacer para que una materia con un alto grado de “asignaturización” como la literatura permita aprendizajes significativos en una lengua extranjera? ¿Cómo motivar e implicar al alumno en el proceso educativo cuando existe un filtro poderoso como es la complejidad del texto literario, más aún si se trata de un usuario básico? Este artículo presenta algunos resultados de la aplicación de una secuencia de actividades en el aula de español de un liceo lingüístico romano. El objetivo es desarrollar la competencia afectiva y metafórica a través de la poesía y afianzar destrezas comunicativas de tipo gramatical, funcional y nocional.

Abstract Epstein–Barr virus (EBV), human herpesvirus 6A/B (HHV-6A/B) and multiple sclerosis (MS)-associated retrovirus (MSRV) have been described as possible MS triggers. We analysed antibody titres against EBV and HHV-6, and MSRV envelope (env) mRNA expression, in the serum of pregnant multiple sclerosis patients (P-MS) to study their possible link to the clinical activity of MS during pregnancy and postpartum and their possible role as relapse predictors. For that purpose, serum samples were collected from 71 pregnant women (50 pregnant MS and 21 pregnant healthy controls—P-HC) during pregnancy and postpartum. Relating to antibody titres, IgM antibody titres against HHV-6A/B were significantly higher in P-MS than in P-HC both in each pregnancy trimester and in the postpartum period. Moreover, IgM antibody titres against HHV-6A/B were higher in P-MS who suffered a relapse during the postpartum. Regarding MSRV env mRNA expression, the prevalence in the first trimester of pregnancy was significantly higher in P-MS who suffered relapses during pregnancy. Summing it up, high IgM antibody titres against HHV-6A/B and MSRV env mRNA expression during the first trimester of pregnancy could act as relapse predictors for the gestation/postpartum periods.

This paper analyzes some of the modalities acquired by endogenous or exogenous bilingualism through the methodology of the case study. I present some linguistic biographies of poets from the historical communities of Spain, as well as from Italy and Latin America interviewed for this research: Fabio Morábito (Italy-Mexico), Gigliola Zecchin (Italy-Argentina), Yolanda Castaño (Spain: Galicia), Josep Maria Rodríguez (Spain: Catalonia) and Vanna Andreini (Italy-Argentina). Also included are comments by the Catalans Joan Margarit and Mireia Vidal-Conte and the Argentines Sylvia Molloy and Adrián Bravi. The study is completed with some reflections on vertical and horizontal self-translation, the role of schooling in bilingual competence and the impact of linguistic contact on the poetic idiolect (code switching, loanwords, calques, allusions, or intertextual quotations) as well as the coining somatic metaphors to describe one’s own bilingualism.

Political Language and Reflections on the Concept of Canon from a Transatlantic Perspective in the First Manifesto of the Movement Poesía ante la incertidumbre. In this article I intend to examine the strengths of Panhispanic or Transatlantic Studies, which represent an appropriate line of research into and analysis of the current circumstances of literature written in Spanish, from a vantage point capable of observing the plurality of changes in the Hispanic-American poetics of twenty-first century works. First of all, I define what is traditionally understood as a literary canon and outline the theoretical support on which I rely to argue my point of view. Secondly, I add the notes of the critics who propose a Transatlantic literary analysis, that is, the ideas of Panhispanism, as a way of analyzing current poetic productions, which I exemplify with the Poetry Facing Uncertainty movement. REZUMAT. Limbaj politic și reflecții asupra conceptului de canon din perspectivă panhispanică în primul manifest al mișcării Poesía ante la incertidumbre. Acest articol își propune să reflecteze asupra coincidenței temporale între redactarea manifestului inițial al mișcării poetice transaltantice Poesía ante la incertidumbre și apariția mișcării 15M sau a indignaților în Spania, ambele având loc în mai 2011, ca fenomen care exemplifică suprapunerea dintre estetic și social. Coincidențele se evidențiază în mărcile intratextuale, discursive, din primul lor manifest ”Apărarea poeziei”, pe care-l vom analiza în acest articol. De asemenea, vom cerceta scopurile principale ale acesti grup, care este încă activ la zece ani de la fondarea sa, precum vocația programatică de a scrie o poezie cu caracter panhispanic. Cuvinte-cheie: canon, studii panhispanice, literatură transaltantică, poezie în spaniolă, Poesía ante la incertidumbre

El presente dossier estudia una serie de corrientes de la poesía hispanoamericana desde 1960 a la actualidad y reconstruye algunas señas de las tradiciones nacionales en las que estas surgieron y evolucionaron (con especial atención a manifestaciones poéticas de Colombia, Nicaragua y México). Se pone en evidencia la expansión de algunas propuestas locales a la cartografía lírica continental a partir de la segunda mitad del siglo pasado (como fue el caso de la poesía conversacional y del compromiso social) para concluir con la identificación de una acentuada orientación panhispánica en el siglo XXI, momento en el que el género manifiesta una creciente liberación de cotos estéticos nacionales en favor de las tradiciones compartidas a ambas orillas del Atlántico, privilegiando el común denominador del idioma. Este dossier nace, entonces, de las reflexiones surgidas en el marco del II Congreso Internacional sobre Poéticas celebrado en junio de 2019 en la Universidad Guglielmo Marconi de Roma, organizado por Alí Calderón y Marisa Martínez Pérsico.

Multiple sclerosis (MS) pathology progressively affects multiple central nervous system (CNS) areas. Due to this fact, MS produces a wide array of symptoms. Symptomatic therapy of one MS symptom can cause or worsen other unwanted symptoms (anticholinergics used for bladder dysfunction produce impairment of cognition, many MS drugs produce erectile dysfunction, etc.). Appropriate symptomatic therapy is an unmet need. Several important functions/symptoms (muscle tone, sleep, bladder, pain) are mediated, in great part, in the brainstem. Cannabinoid receptors are distributed throughout the CNS irregularly: There is an accumulation of CB1 and CB2 receptors in the brainstem. Nabiximols (a combination of THC and CBD oromucosal spray) interact with both CB1 and CB2 receptors. In several clinical trials with Nabiximols for MS spasticity, the investigators report improvement not only in spasticity itself, but also in several functions/symptoms mentioned before (spasms, cramps, pain, gait, sleep, bladder function, fatigue, and possibly tremor). We can conceptualize and, therefore, hypothesize, through this indirect information, that it could be considered the existence of a broad “Spasticity-Plus Syndrome” that involves, a cluster of symptoms apart from spasticity itself, the rest of the mentioned functions/symptoms, probably because they are interlinked after the increase of muscle tone and mediated, at least in part, in the same or close areas of the brainstem. If this holds true, there exists the possibility to treat several spasticity-related symptoms induced by MS pathology with a single therapy, which would permit to avoid the unnecessary adverse effects produced by polytherapy. This would result in an important advance in the symptomatic management of MS.

Introduction: There is an association between rheological alterations and lower extremity deep vein thrombosis, although no research has been carried out regarding the possible influence of rheological alterations in the development of venous thrombosis in the upper limbs. Materials and methods: We have determined in 54 patients (23 male, 31 female; aged 35±11 years) with primary upper extremity deep vein thrombosis (UEDVT), and in a well matched control group of 87 subjects (41 male, 46 female; aged 36±12 years) the rheological profile (blood viscosity, plasma viscosity, fibrinogen, erythrocyte aggregation, erythrocyte deformability) along with plasma lipids (total cholesterol and triglycerides) and body mass index (BMI). Thrombophilic defects (antithrombin, protein C, protein S deficiencies, factor V Leiden, prothrombin G20210A mutation and antiphospholipid antibodies) were also determined. Results: No statistical differences were observed in any of the rheological parameters analyzed (p>0.05), as well as in plasma lipids and BMI (p>0.05) when cases and controls were compared. In investigating the associated factors, we found that more than 60% of events could be explained through effort (28%), thrombophilic defects (19%) and oral contraceptives (26%). Obesity and hyperlipidaemia were not associated with primary UEDVT. Conclusion: Hemorheological alterations do not seem to contribute from a pathogenic point of view to the development of thrombotic events in this infrequent venous location, which is in accordance both with the absence of cardiovascular risk factors and the high shear forces existing in the upper extremity. [ABSTRACT FROM AUTHOR]

Objetivo: Conocer las experiencias de pacientes y cuidadores que conviven con la enfermedad pulmonar obstructiva crónica avanzada, el impacto de sus síntomas y las necesidades de atención que generan en su contexto funcional, emocional y social. Diseño: Estudio cualitativo. Perspectiva fenomenológica. Recogida de datos durante 2013-2015. Emplazamiento: Atención primaria, hospitalaria e intermedia. Osona (Barcelona). Participantes y/o contextos: Diez pacientes de atención primaria con enfermedad pulmonar obstructiva crónica avanzada, 10 cuidadores principales respectivos y 19 profesionales de atención primaria, 2 neumólogos, 2 de cuidados paliativos, implicados en su atención y un psicólogo clínico. Método: Muestreo teórico. Entrevistas semiestructuradas y en profundidad a pacientes, cuidadores y profesionales (47 entrevistas). Resultados: Las temáticas emergentes identificadas en las entrevistas de pacientes y cuidadores hacen referencia a la disnea, síntoma predominante sin un tratamiento efectivo y con un gran impacto en la vida de pacientes y cuidadores. Un síntoma con gran repercusión funcional, emocional y social al que es necesario adaptarse para sobrevivir. Conclusiones: La atención adecuada de los pacientes con enfermedad pulmonar obstructiva crónica, más allá de las medidas farmacológicas para controlar los síntomas respiratorios, pasa por la comprensión del sufrimiento, las pérdidas y las limitaciones que provoca en sus vidas y las de sus cuidadores. Un abordaje paliativo, holístico y cercano a sus vivencias reales, junto al empoderamiento para la adaptación a los síntomas debilitantes, podría contribuir a una vida mejor en la etapa final de la enfermedad.

Objetivos: Demostrar la efectividad de la intervención psicosocial en la atención integral a personas con enfermedades avanzadas. Método: Se ha evaluado la presencia y evolución de parámetros psicológicos y espirituales de 8.964 pacientes, visitados por 117 profesionales de 29 equipos en un estudio de diseño cuasi-experimental, prospectivo, multcéntrico de un solo grupo pre-test post-test. Resultados: Los resultados muestran mejoras significativas en parámetros como ansiedad (RL 657,64; pConclusiones: El efecto positivo de la intervención psicosocial en la reducción de los parámetros psicológicos y espirituales evaluados sugiere que esta es eficaz en el contexto de la atención a personas con enfermedades avanzadas.

En el presente trabajo analizamos tres portales digitales correspondientes a dos editoriales (Teseo y Planeta) y una biblioteca virtual (Cervantes Virtual) con el objetivo de revisar algunos logros y desafíos actuales que enfrentan las políticas del libro en España y Argentina, en un entorno de creciente digitalización. El primer sitio pertenece a un emprendimiento joven cuya labor editorial nació de manos privadas pero como receptora de financiamiento estatal a través de un fondo de estímulo a las incipientes Industrias Culturales. Casi en las antípodas, el segundo sitio pertenece a un conglomerado multimedios, poderoso grupo económico de gran concentración horizontal y vertical. Se desarrolla en el ámbito no sólo de la edición de libros sino también en educación, medios audiovisuales y comunicación. Por último, hemos seleccionado una biblioteca virtual que en la última década se ha convertido en el referente ineludible de la literatura digital en lengua española. Nacida de gestión pública, ahora recibe financiamiento mixto, tanto de la Administración como de empresas privadas, y utiliza los servicios de una plataforma de autopublicación para difundir textos institucionales.

In this issue I intend to study how the Argentine writer Leopoldo marechal (1900-1970) re-elaborates the motif of Revelation in his novel Adán Buenosayres (1948) as well as in two discarded autograph and unpublished pages of the final manuscript. I will review the sketch that Marechal writes, and finally reject, of the legend of the fire theft carried out by a Caracara, among the tobas Indians, as intertext which postulates a creolization of the Promethean story. Will also analyse another two approaches of the Apocalypse in the aforementioned novel: the collapse of the amatory pretensions of the protagonist and the generational Apocalipse, through the interpretation of the death of Adán Buenosayres as a retrospective and critical balance of the ultraista-martinfierrista experience.

Resumen: Este trabajo presenta una experiencia áulica llevada a cabo con estudiantes de nivel secundario en Argentina (años 2001 a 2003) en el marco de un microemprendimiento editorial escolar. Con base en los aportes de la pedagogía para la comprensión y la lingüística textual se mostrarán los resultados obtenidos gracias a un encuadre de enseñanza-aprendizaje que apeló a la tutoría en línea, promovió la transversalidad disciplinaria de la lengua y la literatura en español con otras áreas de conocimiento, y se basó en un método de reescritura y reformulación de textos literarios con el objetivo de favorecer la adquisición de competencias lingüísticas a partir de los contrastes y cotejos efectuados entre alumno y profesor para llegar a una producción final publicable en soporte papel y digital.Abstract: This work presents a classroom experience carried out with students at the secondary level in Argentina (years 2001 to 2003). Based on the contributions of the Pedagogy for Understanding and Textual Linguistics we will show the results obtained thanks to the online tutoring, the disciplinary transversality of the language and literature in Spanish with other areas of knowledge as well as the utilization of a method of rewriting and rephrasing literary texts with the aim of promoting the acquisition of language skills to reach a publishable final production.

This work developes the analysis of blogonovels (and also printed novels) recently published by Hispano-American and Spanish authors, whose structure shows the impact of digital technologies: qualities like the creative and selective interactivity, the technique of composition in atomized chapters, the autobiographical narration, the hipertextuality, fragmentation and rupture of the narrative linearity as well as the colloquial writing. Our investigation also studies the benefits of the ‘virtual space’ in terms of democratization and production of cultural objects.