Experimental and theoretical studies on the effect of the oxo group in 1,4-benzodiazepines

Two families of regioisomeric 1,4-benzodiazepines, 4-benzyl-3H-benzo[e][1,4]diazepin-5-ones and 4-benzoyl-4,5-dihydro-3H-benzo[e][1,4]diazepines, have been synthesized through a similar Ugi/reduction cyclization sequence. Their conformation and stability depend on the position of the tautomeric imine/enamine equilibrium present in the diazepine nucleus, which in turn depends on the relative position of the carbonyl group adjacent to the nitrogen at the 4-position in the benzodiazepine system. Moreover, the electrophilic center on the imine tautomer is essential for the antitumor activity of some benzodiazepines as a DNA binding position. The mechanism of tautomerization in the presence or absence of the oxo group has been studied computationally using DFT methods (B3LYP/6-31G** level).Ministerio de Economía y Competitividad, Spain (project CTQ2012- 31611), from Ministerio de Ciencia e Innovación, Spain and Fondo de Desarrollo Regional (project MAT2011-22781), as well as from Junta de Castilla y León, Consejería de Educación y Cultura y Fondo Social Europeo (project ref. BU246A12-1 and BU327A11-2)

Determination of Sr-90 in milk samples from the study of statistical results

[Abstract] The determination of 90Sr in milk samples is the main objective of radiation monitoring laboratories because of its environmental importance. In this paper the concentration of activity of 39 milk samples was obtained through radiochemical separation based on selective retention of Sr in a cationic resin (Dowex 50WX8, 50-100 mesh) and subsequent determination by a low-level proportional gas counter. The results were checked by performing the measurement of the Sr concentration by using the flame atomic absorption spectroscopy technique, to finally obtain the mass of 90Sr. From the data obtained a statistical treatment was performed using linear regressions. A reliable estimate of the mass of 90Sr was obtained based on the gravimetric technique, and secondly, the counts per minute of the third measurement in the 90Sr and 90Y equilibrium, without having to perform the analysis. These estimates have been verified with 19 milk samples, obtaining overlapping results. The novelty of the manuscript is the possibility of determining the concentration of 90Sr in milk samples, without the need to perform the third measurement in the equilibrium

Local Clergy and Ecclesiastical Reorganization in the Diocese of Leon (11th-13th Centuries)

This paper analyzes the transformations undergone by the local clergy in the diocese of Leon between the mid-eleventh and the beginning of the 13th Century, with a view to shedding light on how this group adjusted to the new framework of ecclesiastical organization promoted by the Gregorian Reform. To this end, the study examines different aspects such as the changes in the ways clergymen were appointed, the subordination of local clergymen to the episcopal jurisdiction, their adjustment to certain standards of discipline and behavior, and their participation in the ecclesiastical income, within a context characterized by the strengthening of episcopal authority and the configuration of the parish system in northern Iberia

Emission polarization control in semiconductor quantum dots coupled to a photonic crystal microcavity

8 páginas, 5 figuras.-- OCIS codes: (160.4760) Optical properties; (230.5298) Photonic crystals; (230.5590) Quantumwell, -wire and –dot devices.We study the optical emission of single semiconductor quantum dots weakly coupled to a photonic-crystal micro-cavity. The linearly polarized emission of a selected quantum dot changes continuously its polarization angle, from nearly perpendicular to the cavity mode polarization at large detuning, to parallel at zero detuning, and reversing sign for negative detuning. The linear polarization rotation is qualitatively interpreted in terms of the detuning dependent mixing of the quantum dot and cavity states. The present result is relevant to achieve continuous control of the linear polarization in single photon emitters.This work has been supported by research contracts of the Spanish Ministry of Education Grants MAT2008-01555/NAN, Consolider CSD 2006-19 and Naninpho-QD TEC2008-06756-C03- 01, and the Community of Madrid Grant Grant CAM (S2009/ESP-1503).Peer reviewe

Intracranial atherosclerotic plaque enhancement and long-term risk of future strokes: A prospective, longitudinal study

Background and Purpose The prognostic significance of postcontrast enhancement of intracranial atheromatous plaque is uncertain. Prospective, long-term follow-up studies in Caucasians, using a multicenter design, are lacking. We aimed to evaluate whether this radiological sign predicts long-term new stroke in symptomatic and asymptomatic intracranial atherosclerotic disease (ICAD) patients. Methods This was a prospective, observational, longitudinal, multicenter study. We included a symptomatic and an asymptomatic cohort of ICAD patients that underwent 3T MRI including high-resolution sequences focused on the atheromatous plaque. We evaluated grade of stenosis, plaque characteristics, and gadolinium enhancement ratio (postcontrast plaque signal/postcontrast corpus callosum signal). The occurrence of new events was evaluated at 3, 6, 9, and 12 months and annually thereafter. The association between plaque characteristics and new stroke was studied using Cox multiple regression survival analysis and Kaplan-Meier curves. Results Forty-eight symptomatic and 13 asymptomatic patients were included. During 56.3 ± 16.9 months, 11 patients (18%) suffered a new event (seven ischemic, two hemorrhagic, and two transient ischemic attacks). A receiver operating characteristic curve identified an enhancement ratio of >1.77 to predict a new event. In a multivariable Cox regression, postcontrast enhancement ratio >1.77 (hazard ratio [HR]= 3.632; 95% confidence interval [CI], 1.082-12.101) and cerebral microbleeds (HR = 5.244; 95% CI, 1.476-18.629) were independent predictors of future strokes. Patients with a plaque enhancement ratio >1.77 had a lower survival free of events (p < .05). Conclusions High intracranial postcontrast enhancement is a long-term predictor of new stroke in ICAD patients. Further studies are needed to elucidate whether postcontrast enhancement reflects inflammatory activity of intracranial atheromatous plaque.This study has been funded by the Spanish Ministry of Science, via FIS project PI13/02544, PI16/01396, and PI19/01398 and through the INVICTUS PLUS research network RD16/0019. Beatriz Gómez-Vicente received a research contract from the Junta de Castilla y León and European Social Fund, Spain. María Hernandez-Perez was funded by The Instituto de Salud Carlos III, Spain (JR17/00006)

Brain atrophy and the risk of futile endovascular reperfusion in acute ischemic stroke

[Background and Purpose]: We aimed to evaluate the impact of brain atrophy on long-term clinical outcome in patients with acute ischemic stroke treated with endovascular therapy, and more specifically, to test whether there are interactions between the degree of atrophy and infarct volume, and between atrophy and age, in determining the risk of futile reperfusion.[Methods]: We studied consecutive patients with acute ischemic stroke with proximal anterior circulation intracranial arterial occlusions treated with endovascular therapy achieving successful arterial recanalization. Brain atrophy was evaluated on baseline computed tomography with the global cortical atrophy scale, and Evans index was calculated to assess subcortical atrophy. Infarct volume was assessed on control computed tomography at 24 hours using the formula for irregular volumes (A×B×C/2). Main outcome variable was futile recanalization, defined by functional dependence (modified Rankin Scale score >2) at 3 months. The predefined interactions of atrophy with age and infarct volume were studied in regression models.[Results]: From 361 consecutive patients with anterior circulation acute ischemic stroke treated with endovascular therapy, 295 met all inclusion criteria. Futile reperfusion was observed in 144 out of 295 (48.8%) patients. Cortical atrophy affecting parieto-occipital and temporal regions was associated with futile recanalization. Total global cortical atrophy score and Evans index were independently associated with futile recanalization in an adjusted logistic regression. Multivariable adjusted regression models disclosed significant interactions between global cortical atrophy score and infarct volume (odds ratio, 1.003 [95%CI, 1.002–1.004], P<0.001) and between global cortical atrophy score and age (odds ratio, 1.001 [95% CI, 1.001–1.002], P<0.001) in determining the risk of futile reperfusion.[Conclusions]: A higher degree of cortical and subcortical brain atrophy is associated with futile endovascular reperfusion in anterior circulation acute ischemic stroke. The impact of brain atrophy on insufficient clinical recovery after endovascular reperfusion appears to be independently amplified by age and by infarct volume.This study has been partially funded by the Spanish Ministry of Science, via FIS projects PI13/02544 and PI16/01396, and through the INVICTUS PLUS research network RD16/0019.Peer reviewe

Spanish home enteral nutrition registry of the year 2014 and 2015 from the NADYA-SENPE Group

Objetivo: exponer los resultados del registro de nutrición enteral domiciliaria (NED) del año 2014 y 2015 del Grupo NADYA-SENPE. Métodos: se recopilaron los pacientes introducidos en el registro desde el 1 de enero al 31 de diciembre de 2014 y la mismas fechas de 2015, y se procedió al análisis descriptivo y analítico de los datos. Resultados: en el año 2014, se registraron 3.749 pacientes y en 2015, 4.202; la prevalencia fue de 80,58 pacientes/millón de habitantes en el año 2014 y de 90,51 en 2015. Por sexos, hubo un 49,9% de mujeres en 2014 y un 50,3% en 2015. La edad media fue de 73 años (IIQ 59-83) en ambos años. Finalizaron 684 episodios de NED en 2014 y 631 en 2015, la causa principal fue el fallecimiento en el 54,9% y 50,4% de los casos, respectivamente. Los portadores de sonda nasogástrica presentan una edad media superior a los pacientes con cualquier otra vía (p < 0,001). Se registraron 67 pacientes pediátricos en 2014 (56,7% niñas) y 77 en 2015 (55,8% niñas). La vía principal de administración fue la gastrostomía en el 52,0% de los casos de 2014 y sonda nasogástrica en el 50,8% de los casos de 2015. La causa principal de fi nalización de la nutrición fue el fallecimiento (57,1% en 2014 y 38,5% en 2015). Se observó que los niños más pequeños eran los que se alimentaban preferentemente por SNG (p 0,004 vs. 0,002).Tanto en pacientes pediátricos como en adultos el diagnóstico principal que motivó la necesidad de NED fue la enfermedad neurológica que cursa con afagia o disfagia severa. Conclusiones: se ha incrementado el número de pacientes del registro, así como el número de centros participantes y el número medio de pacientes comunicados por cada centro respecto a años anteriores, sin que se hayan modificado sustancialmente las características de los pacientes, salvo mayor duración de los episodiosObjective: To present the results of the Spanish home enteral nutrition (HEN) registry of the NADYA-SENPE group for the years 2014 and 2015. Methods: From January 1st 2014 to December 31st 2015 the HEN registry was recorded and afterwards a further descriptive and analytical analysis was done. Results: In 2014, 3749 patients were recorded, and 4202 in 2015; prevalence was 80.58 patients/one million inhabitants in Spain in 2014 and 90.51 in 2015. There were 49.9% females in 2014 and 50.3% in 2015. Median age was 73 years (IQI 59-83) in 2014 as well as in 2015. 684 episodes fi nished in 2014 and 631 in 2015, with death as the main cause, in 54.9% and 50.4%, respectively. The ones who were fed through nasogastric tube had a mean age higher than the ones fed by any other route (p-value < 0.001). Sisty-seven paediatric patients were recorded in 2014 (56.7% females) and 77 in 2015 (55.8% females). Median age at the beginning of HEN among children was 5 months in 2014 and 5 months in 2015. The main route of administration was gastrostomy, in 52.5% in 2014 and nasogastric tube in 50.8% in 2015. 7 episodes fi nished in 2014 and 13 in 2015, having death as the main cause (57.1% in 2014 and 38.5% in 2015). It was found that were younger children the ones who were mainly fed by nasogastric tubes (p-value 0.004 vs. 0.002). Among paediatric patients as well as adults, the main diagnosis leading to HEN was neurological disease which gives aphagia or severe dysphagia. Conclusions: There has been an increase in the number of patients in the registry as well as the participating centers and the number of patients per center, without any signifi cant change in the characteristics of the patients other than longer duration of the episode

IL-6 serum levels predict severity and response to tocilizumab in COVID-19: An observational study

Background: Patients with coronavirus disaese 2019 (COVID-19) can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome requiring invasive mechanical ventilation (IMV). Because IL-6 is a relevant cytokine in acute respiratory distress syndrome, the blockade of its receptor with tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19. Objective: We sought to determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ. Methods: A retrospective observational study was performed in hospitalized patients diagnosed with COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with preadministration and postadministration of TCZ. Multivariable logistic and linear regressions and survival analysis were performed depending on outcomes: need for IMV, evolution of arterial oxygen tension/fraction of inspired oxygen ratio, or mortality. Results: One hundred forty-six patients were studied, predominantly males (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels greater than 30 pg/mL was the best predictor for IMV (odds ratio, 7.1; P < .001). Early administration of TCZ was associated with improvement in oxygenation (arterial oxygen tension/fraction of inspired oxygen ratio) in patients with high IL-6 (P = .048). Patients with high IL-6 not treated with TCZ showed high mortality (hazard ratio, 4.6; P = .003), as well as those with low IL-6 treated with TCZ (hazard ratio, 3.6; P = .016). No relevant serious adverse events were observed in TCZ-treated patients. Conclusions: Baseline IL-6 greater than 30 pg/mL predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administrationThis study was funded by Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and Instituto de Salud Carlos III (grant nos. RD16/0011/0012 and PI18/ 0371 to I.G.A., grant no. PI19/00549 to A.A., and grant no. SAF2017-82886-R to F.S.-M.) and co-funded by the European Regional Development Fund. The study was also funded by ‘‘La Caixa Banking Foundation’’ (grant no. HR17-00016 to F.S.-M.) and ‘‘Fondos Supera COVID19’’ by Banco de Santander and CRUE. None of these sponsors have had any role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publicatio

Humanizar emprendiendo: homenaje a Rafael Alvira

Este cuaderno contiene "El Instituto y Rafael Alvira" "La carta 9 de Séneca" "Rafael Alvira: la castiza filosofía del hombre que vuelve" "Añoranza del humanismo necesario" "Una reflexión filosófica sobre lo económico: comentario a un texto de Rafael Alvira" "La dimensión societaria de la economía y de la empresa" "Sobre el espíritu aristocrático y el empresario: responsabilidades de ayer, responsabilidades de hoy" "Sobre el sistema de los derechos del hombre: el punto de vista de Charles Péguy" "El hogar familiar: espacio de lo eterno" "¿Filosofar con el martillo o con la empresa?" "Qué queremos decir cuando hablamos de desarrollo" "Tipologías de la información económico-financiera en la empresa. Valores y valoración" "Rafael Alvira y la Universidad de Montevideo" "Breve introducción al examen sistemático de “Cristianismo y empresarialidad”" "La realidad del poder en la familia y en la empresa familiar" "El todo y la parte. Alabanza de la sinécdoque" "Las raíces del liderazgo auténtico. Una fenomenología básica" "Algunas consideraciones sobre el poder político

Architectural Systemic Approach: The Serpentine Gallery 2005, a Reciprocal Frame Case Study

The application of the systemic approach in architecture aims to promote an integral, holistic view of the architectural design process. The literature reviewed calls for models with systemic behavior, and for these models to be applied in concrete cases. This paper proposes an original approach, using the foundation matrix and the constructive logic matrix. Both matrices are part of a developing model that is being tested on a case study. The work presented here had two objectives: to check this part of the model and gain more knowledge about the model itself. The selected case study, the 2005 Serpentine Gallery Pavilion, is a contemporary ephemeral construction of significant architectural interest. It is a reciprocal frame structure, linked to the construction history. The methodology used was a systemic analysis. In the first phase of the analysis, the reciprocal structures documented historically in the West were reviewed. The other two phases corresponded to the application of the two model matrices. Conceptual diagramming was used in all phases of the process. The results show the importance of the study of historical building solutions. The use of matrices facilitates the identification and understanding of the operations carried out in the design process of the case study. Matrices favor the organization of concepts and relationships from through a systemic approach. Understanding generation operations in an integrated way leads to a type of knowledge (relational knowledge) that allows architecture to be thought about in a holistic way. This makes the systemic view of art and technology as a unit possible, attending to the whole complexity of architectural thinking