María Zambrano and the Concept of Person

Di fronte alla crisi dell’uomoeuropeo contemporaneo, Zambranoriflette sulla nascita, o meglio,sulla rinascita di quest’ultimo,percorrendo un cammino di carattereauto-coscienziale. Punto dipartenza fondamentale è, dunque,la prospettiva antropologica da cuimuove la filosofia zambraniana.Questa breve analisi prende inconsiderazione alcuni elementiessenziali, utili alla comprensionedell’idea di persona: il confrontocon il concetto di individuo;l’ordo amoris; la trascendenza.Tutti questi aspetti permettonodi cogliere i punti di contattocon alcuni degli autori che hannomaggiormente influenzato lariflessione filosofica di Zambrano,come M. Scheler e Sant’Agostino.Si aggiunge, inoltre, un rapidoconfronto con il pensiero diS. Weil e di E. Mounier.Facing the crisis of the contemporaryEuropean man, Zambranomeditates on his birth,or better, on his rebirth througha path of self-consciousness.The point from which Zambranianphilosophy departs is theanthro-pological perspective, andin this sense the analysis considerssome essential aspects, all ofthem useful in understanding theidea of person: the comparisonwith the concept of individual;the ordo amoris, and transcendence.These three elements allowus to identify the contact pointsbetween Zambrano and some ofthe authors who influenced herphilosophical reflections, suchas M. Scheler and Saint Augustine.Finally, this paper offers asynthetic comparative analysiswith the thoughts of S. Weil andE. Mounier

Caractériser l'épuisement lymphocytaire T global ou donneur-spécifique après transplantation rénale : analyse phénotypique et fonctionnelle

L'utilisation d'une immunosuppression (IS) au long cours reste indispensable après transplantation, même si le phénotype des rejets se modifie avec le délai de greffe. Cependant, les complications liées à la sur- IS (néoplasies, infections...), ou sous- IS (rejet aigu ou chronique) réduisent toujours la survie des patients ou des greffons. Améliorer la compréhension des mécanismes lymphocytaires impliqués dans les modifications des réponses allo-spécifiques ou non spécifiques après greffe est importante pour individualiser la prescription des immunosuppresseurs et limiter leurs complications. Une altération des fonctions lymphocytaires T peut survenir au cours des mécanismes allo-immuns, ou sous traitement immunosuppresseur au long cours. L'épuisement lymphocytaire T (ELT) caractérise un état de dysfonction affectant les lymphocytes T mémoires, dans des situations de stimulation chronique avec persistance de l'exposition à un antigène. Cet état est caractérisé par une baisse des capacités prolifératives ou fonctionnelles de ces cellules, et la co-expression de récepteurs inhibiteurs (RIs). Bien que des modèles murins aient récemment souligné le rôle de l'ELT dans le rejet de greffe, cet état dysfonctionnel reste peu étudié. Dans une première étude, nous avons analysé l'expression de 3 RIs classiquement associés à l'ELT (2B4 (CD244), Programmed cell Death protein (PD)-1), et CD160, au cours du traitement par anti-PD1 (nivolumab) de 3 transplantés rénaux présentant une leucoencéphalopathie multifocale progressive. L'analyse des RIs dans les CD4+ et CD8+ a montré des taux élevés d'expression de 2B4, PD-1, et CD160 avant traitement, suggérant un ELT. Après traitement, seule l'expression de PD-1 diminuait, alors que les autres RIs n'étaient pas affectés par l'utilisation du traitement, suggérant la persistance de cet dysfonction lymphocytaire. Par la suite, nous avons cherché par une étude transversale à caractériser l'ELT dans une population de patients exposés à de forts niveaux d'IS, les patients greffés avec anticorps spécifiques du donneur préformés (greffes HLA incompatibles, HLAi). Ces patients recevaient tous une induction par sérum anti-lymphocytaire et rituximab, ainsi qu'un traitement de maintenance par tacrolimus, acide mycophenolique, et corticoides. Afin de comparer l'expression des RIs (PD-1, Tigit, 2B4) et les capacités de production cytokinique (IFNgamma, TNFalpha, IL2) de ces patients, nous avons utilisé un groupe de patients greffés en incompatibilité ABO (greffes ABOi) recevant un traitement d'induction et de maintenance similaire, mais exposé à un antigène dont la réponse est T-indépendante. Nous avons pu observer une augmentation de la co-expression des récepteurs inhibiteurs dans le groupe de patients HLAi en comparaison aux patients ABOi. Particulièrement, Tigit présentait un niveau d'expression dans les CD4 et CD8 du groupe HLAi plus élevé comparativement aux ABOi. De plus, alors que Tigit était négativement corrélé aux capacités fonctionnelles des LT du groupe ABOi, toute corrélation était perdue dans le groupe HLAi. Ces données suggèrent que l'ELT au cours de la reconstitution lymphocytaire serait plus important après greffe HLAi, ce qui est cohérent avec le niveau élevé de complications infectieuses et néoplasiques décrites après ce type de greffe. Dans une deuxième étude transversale portant sur des patients transplantés rénaux, libres de toute complication infectieuse, néoplasique, allo-immune, et sous traitement immunosuppresseur standard, nous avons montré une corrélation positive entre le délai de greffe et l'expression de Tigit dans les CD4 mémoires, alors que la proportion de cellules CD4+ TIGIT-CD226+ diminuait. L'analyse fonctionnelle de ces cellules nous a permis de montrer une dysfonction de l'axe Tigit/CD226 au cours du temps dans les CD4 mémoires. Dans les CD8 mémoires, nous avons pu montrer un profil dysfonctionnel de ces cellules, associé à une augmentation d'expression des cellules CD8+PD-1+Tigit+. La réponse allo-spécifique (approchée par réaction lymphocytaire mixte) était diminuée en comparaison à la réponse non-spécifique, et corrélée au pourcentage de cellules mémoires CD4+Tigit+CD226+Tim3-PD-1-2B4- avant stimulation. Enfin, nous avons étudié les différences immunologiques T et B au cours de formes modérées et graves du COVID-19 chez des patients transplantés d'organe solide, et montré des différences immunologiques majeures au sein des différents compartiments entre les deux groupes. Par ces différents travaux nous avons montré que l'ELT pourrait être impliqué dans la diminution progressive des rejets T-médiés après greffe. La caractérisation d'une signature d'ELT post greffe pour limiter les complications liées à l'IS parait utile pour améliorer les résultats post-transplantation.Kidney transplantation requires the long-term use of immunosuppressive therapy (IT) even if a modification of rejections phenotype with time was previously noted. However, patient and graft survival remain entailed by over-IT (e.g cancer and infections), or under-IT (e.g acute or chronic rejections) complications. A better comprehension of immune mechanisms involved in changes concerning global or allo-specific responses is a key point to improve the individualization of IT and decrease IT-related complications. Several dysfunctional states could occur during allo-immune response, or on long-term immunosuppressive therapy. T cell exhaustion (TCE) is a dysfunctional state affecting memory T cells during chronic stimulation due to the persistent exposure of a high load of foreign antigen. This state is characterized by a decrease proliferative capacity, reduced production of cytokines, and is associated with co-expression of inhibitory receptors (IRs) expression. Murine models of solid organ transplantation suggested a role for T cell exhaustion. However, until now this dysfunctional state is barely studied after transplantation. We first analyzed the expression of 3 IRs classically associated with T cell exhaustion (2B4 (CD244), Programmed cell Death protein (PD)-1), and CD160), in 3 kidney transplant recipients treated with anti-PD1 (nivolumab) therapy for progressive multifocal leukoencephalopathy. Before treatment, we observed a high-level expression of IRs in both CD4 and CD8+ T cells, suggesting T cell exhaustion. After treatment, PD-1 expression, but not of others IRs, decreased, suggesting the persistence of this dysfunctional state, strengthened by the absence of clinical improvement. We next investigated TCE in a cross-sectional study in a highly immunocompromised population, patients with preformed donor-specific antibodies (HLA incompatible, HLAi). All included patients received anti-lymphocyte globulins and anti-20 antibodies (rituximab), followed by a maintenance therapy (tacrolimus, mycophenolic acid, and steroids). We compared IRs expression ( PD-1, Tigit, 2B4) and cytokine production (IFNgamma, TNFalpha, IL2) of these patients to ABO incompatible recipients that received the same induction and maintenance therapy, but was exposed to a T-independent response antigen. We observed an increased co-expression of IRs in the HLAi group comparing with ABOi. Especially, Tigit expression was expressed in higher levels by CD4+ and CD8+ T cells in HLAi comparing with ABOi. Moreover, while Tigit was as expected negatively correlated with functional capacities in ABOi patients, we did not observe any correlation between Tigit expression and function in HLAi recipients. These data suggest that TCE during reconstitution of HLAi patients would be more important than in ABOi recipients, which is consistent with the higher rate of infectious and neoplastic complications previously reported in this group. Thereafter, we performed a second cross-sectional study a living-donor kidney transplant recipients, free from infectious, neoplastic, alloimmune complications, and receiving a standard immunosuppressive maintenance therapy (no induction, maintenance with tacrolimus, mycophenolic acid, steroids). We observed a positive correlation between time post transplantation and Tigit expression in memory CD4+ T cells, while the proportion of CD4+Tigit-CD226+ decreased. Functional analysis of these cells revealed a dysfunctional state of Tigit/ CD226 axis with time post transplantation in memory CD4. In memory CD8+ T cells, we observed a dysfunctional profile of these cells with time post transplantation, associated with an increased proportion of CD8+PD-1+Tigit+ cells. Donor-specific response, investigated by the mean of mixed lymphocyte reaction, was reduced comparing with third-parties responses, and was correlated to the percentage of CD4+Tigit+CD226+Tim3-PD-1-2B4- before stimulation. Finally, we studied T and B cells differences during moderate and severe forms of COVID-19 in solid organ transplant recipients. We observed accurate immunological differences between mild and severe forms (lower CD3+ and CD8+ T cells number, higher proportion of activated CD4+ T cells and lower proportion of regulatory T cells, NK cells, and transitional B cells in severe forms). This work suggests that TCE could be involved in the progressive decrease of T cell rejection post transplantation. Characterizing a post-transplant TCE signature to reduce immunosuppression-related complication appears to be usefull to improve post-transplant outcomes

Currency Crises During the Great Recession: Is This Time Different?

During the 2007-2009 financial crisis the foreign exchange market was characterized by large volatility and wide currency swings. In this paper we evaluate whether during the period of the Great Recession there has been a structural break in the relationship between fundamentals and exchange rates within an early-warning framework. This is done by extending the original data set by Kaminsky and Reinhart (1999) and including not only the most recent period, but also 17 new countries. Our analysis considers two variations of the original early-warning system. First, we propose two new methods to obtain the probability distribution of the early-warning indicator (conditional on the occurrence of a crisis) – one fully parametric and one based on a novel distribution-free semi-parametric approach. Second, we compare the original early-warning indicator with a core indicator that includes only “pseudo-financial variables” (domestic credit/GDP, the real exchange rate, international reserves and the real interest-rate differential) and we evaluate their performance not only for currency crises during the Great Recession, but also for the Asian Crisis. All tests make us conclude that “this time is different”, i.e. early-warning systems based on traditional macroeconomic variables have not only failed to forecast currency crises during the Great Recession, but have also significantly worsened with respect to the period of the Asian crisis.Early Warning Systems; Exchange Rates; Semi-parametric Meth- ods

An analytical model for gas overpressure in slug-driven explosions:insights into Strombolian volcanic eruptions

Strombolian eruptions, common at basaltic volcanoes, are mildly explosive events that are driven by a large bubble of magmatic gas (a slug) rising up the conduit and bursting at the surface. Gas overpressure within the bursting slug governs explosion dynamics and vigor and is the main factor controlling associated acoustic and seismic signals. We present a theoretical investigation of slug overpressure based on magma-static and geometric considerations and develop a set of equations that can be used to calculate the overpressure in a slug when it bursts, slug length at burst, and the depth at which the burst process begins. We find that burst overpressure is controlled by two dimensionless parameters: V', which represents the amount of gas in the slug, and A', which represents the thickness of the film of magma that falls around the rising slug. Burst overpressure increases nonlinearly as V' and A' increase. We consider two eruptive scenarios: (1) the "standard model," in which magma remains confined to the vent during slug expansion, and (2) the " overflow model," in which slug expansion is associated with lava effusion, as occasionally observed in the field. We find that slug overpressure is higher for the overflow model by a factor of 1.2-2.4. Applying our model to typical Strombolian eruptions at Stromboli, we find that the transition from passive degassing to explosive bursting occurs for slugs with volume >24-230 m(3), depending on magma viscosity and conduit diameter, and that at burst, a typical Strombolian slug (with a volume of 100-1000 m(3)) has an internal gas pressure of 1-5 bars and a length of 13-120 m. We compare model predictions with field data from Stromboli for low-energy " puffers," mildly explosive Strombolian eruptions, and the violently explosive 5 April 2003 paroxysm. We find that model predictions are consistent with field observations across this broad spectrum of eruptive styles, suggesting a common slug-driven mechanism; we propose that paroxysms are driven by unusually large slugs (large V')

How does the treadmill affect gait in Parkinson’s disease?

[Abstract] Parkinson’s disease (PD) is clinically characterized by symptoms of akinesia, rigidity, and resting tremor, which are related to a dopaminergic deficiency of the nigrostriatal pathway. Disorders of gait are common symptoms of PD that affect the quality of life in these patients. One of the main focuses of physical rehabilitation in PD is to improve the gait deficits in the patients. In the last decade, a small number of studies have investigated the use of the treadmill for the rehabilitation of gait in PD patients. Although, the results of these studies are promising, the mechanisms underlying the therapeutic effect of the treadmill in PD are still largely unknown. This paper reviews 10 years of investigation of treadmill training in PD, focusing on the possible mechanisms involved in the therapeutic effect of the treadmill. Understanding these mechanisms may improve the prescription and design of physical therapy programs for PD patients.Ministerio de Ciencia e Innovación; PSI2008-03175Xunta de Galicia; 2009/00

El bacalao en España (1850-1914): importación y política comercial

Spain has traditionally been the largest consumer market for salted cod. However, despite Spain’s important presence in the international cod market and the contribution it has made to Spanish tax revenue throughout much of the nineteenth and early twentieth century, most of the literature has addressed the issue as part of broader studies of the primary sector, consumption patterns or other matters that generally focused on the demand side. This article seeks to remedy this deficiency, placing the theme as an object of study in itself and using a supply side approach. First, we have reconstructed import market statistics, examining the relative weight of cod to total import figures and measuring their significance in relation to the revenue of the Spanish Treasury. Second, we have determined the geographical origins of imported cod and its fluctuations over time. The final part of the essay is devoted to the salted cod trade and tariff policies adopted by the Spanish government. The period examined here, 1850-1914, covers a span that extends from the earliest Spanish foreign trade statistics to the First World War, when global cod markets experienced dramatic changes

Transcranial magnetic stimulation over dorsolateral prefrontal cortex in Parkinson’s disease

[Abstract] Objective Several studies have shown that repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) is effective in the treatment of depression in patients with Parkinson disease (PD). However, since research into the effect of this type of rTMS regime on motor function is limited, we studied the effect of rTMS over the DLPFC on the motor functions in PD patients. Methods Thirteen patients were randomly assigned into 2 groups, one receiving real-rTMS (90% of resting motor threshold, 10 Hz, 450 pulses-day for 10 consecutive days) over the DLPFC contralateral to the more affected side, and the other group receiving sham-rTMS. Assessment included a clinical motor evaluation using part III of the Unified Parkinson’s Disease Rating Scale (UPDRS), and several motor tasks. The UPDRS was applied before and after 10 days of rTMS. Finger tapping, reach movement, grip movement and gait were measured in each session before and after the rTMS over the 10 day period. Results Statistical analysis (ANOVA for repeated measures; group ∗ day ∗ side ∗ rTMS) only showed a significant effect for finger tapping, reach movement and gait for the factor day. No significant change was reported for the UPDRS in any group. Conclusions Application of rTMS over the DLPFC as a 10 day course had no significant effect on motor functions and clinical motor status, and the improvement in performance of motor tasks can be attributed to the effects of practice. Significance rTMS over the DLPFC did not lead to any motor improvement in PD patients

Neighborhood Effects in Education

Using unique geo-coded information on the residential address of a representative sample of American adolescents and their friends, we revisit the importance of geographical proximity in shaping education outcomes. Our findings reveal no evidence of residential neighborhood effects. Social proximity, as measured by similarity in religion, race and family income as well as in unobserved characteristics, appears to play a major role in facilitating peer influence. Our empirical strategy is able to control for the endogeneity of both social network and location choices

Control del efectivo en la organización Talentum

Síntesis AplicadaSíntesis Aplicada en Talentum SAS, consistió en identificar los riesgo en el manejo de efectivo, en valorar y analizar los informes financieras para conocer la situación actual financiera de la organización y poder proponer alternativas que mejorarán optima y eficientemente dicha situación financiera y en especial en el departamento de cartera de la organización.RESUMEN. INTRODUCCIÓN 1. DESCRIPCIÓN Y FORMULACIÓN DEL PROBLEMA 2. OBJETIVOS 3. DATOS DE LA INSTITUCIÓN 4. FACTORES DE RIESGO EN LA GESTIÓN DE CARTERA 5. VALORACIÓN INFORMES FINANCIEROS 6. PROPUESTA 7. CONCLUSIONES 8. RECOMENDACIONES BIBLIOGRAFÍAEspecializaciónEspecialista en Análisis y Administración Financier