Magnetic nanoparticles studied by synchrotron radiation and rf transverse susceptibility

Las propiedades magnéticas de los sistemas de nanopartículas son totalmente novedosas y han sido y continúan siendo estudiadas con detalle por numerosos grupos alrededor del mundo, debido a sus posibles aplicaciones y a las nuevas propiedades físicas que se manifiestan a esta escala. Tales aplicaciones van desde dispositivos magnéticos de alto rendimiento [1-3], biomedicina [4, 5] e imágenes por resonancia magnética (IRM) [6, 7]. Cada una de estas aplicaciones requiere partículas con características específicas, para lo cual es indispensable la comprensión y el control de sus propiedades como su anisotropía magnética e interacciones dipolares entre partículas. Por tal motivo, es fundamental emplear diferentes técnicas experimentales para la completa caracterización estructural y magnética de los sistemas de nanopartículas . De ahí que esta memoria esté enfocada en la descripción de diversos estudios en sistemas de nanopartículas magnéticas, donde una adecuada combinación de métodos de caracterización estructural, electrónica y magnética nos ha permitido tener un mayor entendimiento de sus propiedades, en particular de su anisotropía magnética. En la primera parte de esta memoria empleamos técnicas de radiación de sincrotrón, especialmente aquellas basadas en espectroscopías de absorción de rayos X: espectroscopía de Estructura Fina por Absorción de Rayos X (XANES de X­ray Absorption Near Edge Structure y EXAFS de Extended X-ray Absorption Fine Structure) y Dicroísmo Circular Magnético de Rayos X (XMCD de X-ray Mag­netic Circular Dichroism). En las últimas décadas se ha demostrado la potencia y funcionalidad de estas técnicas para el estudio de fenómenos en la nanoescala, ya que permiten obtener de forma directa y selectiva información acerca del estado electrónico, la estructura local y los momentos magnéticos orbital y espinorial de los átomos que componen las partículas. En consecuencia, se han conseguido avances importantes en el papel desempeñado por el momento orbital en la generación de la anisotropía magnética de los sistemas de nanopartículas. Principalmente, se ha puesto de manifiesto la relevancia de acoplamiento espín-órbita en los sistemas de dimensiones nanométricas. Así, el estudio de sistemas de nanopartículas que presentamos en esta memoria continúa trabajos previos desarrollados en el grupo de investigación sobre el aumento de anisotropía en sistemas de nanopartículas de Co debido a efectos espín-órbita por medio de técnicas de radiación de sincrotrón [8, 9]. Estos sistemas de nanopartículas son preparados por deposición tipo "sputtering" secuencial de Alúmina, Co y un metal que cubre las partículas. En esta ocasión hemos explorado la introducción de elementos no magnéticos con alto spín-órbita en tal cubrimiento para mejorar la anisotropía magnética de las partículas de Co: estudiamos su comportamiento al recubrirlas con W y Pt. Así, hemos realizado la correspondiente caracterización estructural de las nanopartículas de Co-W y Co-Pt por medio de técnicas de microscopia electrónica y de Espectroscopía de Estructura Fina por Absorción de Rayos X (EXAFS de Extended X -ray Absorption Fine Structure), esta última en fuentes de radiación de sincrotrón, técnicas que permiten obtener la morfología y estructura local de las partículas. Asimismo, la caracterización magnética de las partículas ha incluido tanto medidas macroscópicas por magnetometría SQUID convencional, como microscópicas por XMCD. También hemos explorado la estructura electrónica de los átomos por medio de técnicas de absorción de rayos X, medidas en energías cercanas a los umbrales de absorción (XANES de X-ray Absorption Near Edge Structure). En estos estudios, hemos observado la producción de aleaciones entre el Co y el metal de cubrimiento y hemos demostrado que la estructura local de tales aleaciones son determinantes en las propiedades de anisotropía magnética de las partículas. Las técnicas selectivas de espectroscopía de absorción de rayos X también permiten explorar el magnetismo de sistemas de nanopartículas de metales nobles. Estas estructuras presentan fenómenos magnéticos interesantes que no se dan en el metal masivo. En esta memoria presentamos una revisión del magnetismo de la banda d en nanoparticulas de metales nobles: Ag, Au, Pd y Pt. Con este estudio aportamos claves para la comprensión de sus propiedades magnéticas. Además de las técnicas de radiación de sincrotrón, la anisotropía magnética de sistemas de nanopartículas puede ser estudiada con medidas de magnetometría en laboratorios convencionales. Una de las técnicas poco exploradas, pero que permite obtener directamente parámetros relacionados con la anisotropía magnética es la medida de la susceptibilidad transversal [10]. Esta técnica consiste en la aplicación de un campo magnético constante (dc) en una dirección de la muestra a estudiar, junto con un campo variable en el tiempo (ac) en la dirección perpendicular. El método de medida está basado en un circuito oscilador acoplado a un tanque LC, donde la muestra se introduce en la bobina que forma dicho circuito resonante. Cualquier cambio en las propiedades físicas del material con el campo o la temperatura, inducen un cambio en la inductancia del circuito, y por tanto en la frecuencia de resonancia. La frecuencia de resonancia del circuito se mide con gran precisión con lo que este método es de alta sensibilidad [10]. Esta técnica ha demostrado su efectividad en el estudio de la anisotropía magnética de diversos sistemas nanoestructurados [11, 12]. Avances previos en esta técnica de susceptibilidad transversal han permitido su implementación en el equipo de medidas físicas (PPMS de physical properties mea­surement system) de Quantum Design [10], frecuentemente usado por la comunidad científica en el mundo. Por tanto, en la segunda parte de esta memoria presentamos el desarrollo de un sistema de medidas de susceptibilidad magnética transversal que se ha puesto en funcionamiento en el PPMS con el que cuenta el Servicio de Medidas Físicas de la Universidad de Zaragoza. En este desarrollo hemos mejorado muchos aspectos del diseño, la electrónica y la adquisición de datos de los susceptometros transversales hasta ahora descritos en la literatura [10]. Asimismo, hemos descrito el uso de esta instalación para explorar las propiedades de anisotropía magnética de dos sistemas de nanopartículas de oxido de hierro, que son especialmente interesantes para las aplicaciones biomédicas. Igualmente, otros usuarios del servicio de medidas físicas pueden continuar beneficiándose de tal instalación para realizar estudios de propiedades magnéticas de interés en diversas muestras, tales como campos de anisotropía, dinámica de espín, correlaciones de corto alcance, entre otras. En esta memoria demostramos el buen funcionamiento del equipo y las potencialidades que ofrece el hecho de tener un sistema de medida de este tipo dentro de las instalaciones de la Universidad de Zaragoza

Molecular diffusion on surfaces: The diffusive behavior of aromatic compounds absorbed on graphitic surfaces studied with Quasi-Elastic-Neutron Scattering (QENS)

Este trabajo está dedicado al estudio de la dinámica de anillos aromáticos en fase adsorbida sobre el plano basal de microcristales de grafito, (es decir la familia de planos cuya dirección normal es paralela a la dirección [0001]). Se trata de un trabajo experimental basado en técnicas de dispersión quasi-elástica de neutrones. Hemos medido con técnicas espectroscópicas de tiempo de vuelo, la difusión de benceno hidrogenado, C6H6, para cuatro recubrimientos: desde 0.1 ML (sólo un 10 % de los sitios de adsorpción están ocupados), 0.2 ML, 0.5 ML y 1.0 ML (el 100 % de los sitios de adsorbción están ocupados) y la difusión de benceno deuterado, C6D6, para recubrimientos de 0.5 ML y 0.9 ML. Además hemos explorado un amplio rango de temperaturas: desde 60 K hasta 140 K, siendo la temperatura de desorpción del benceno en grafito de 150 K [1]. Observamos que la dinámica de las moléculas es muy sensible al recubrimiento. A bajos recubrimientos (0.1ML) las moléculas cumplen un régimen balístico mientras que a medios y altos recubrimientos (a partir de 0.2 ML) la difusión es Browniana. Podemos extraer del análisis de los espectros la velocidad cuadrática promedia de las moléculas en régimen balístico y que satisfacen el principio de equipartición de la energía. En el caso de recubrimientos por encima de 0.2 ML hemos obtenido los parámetros de fricción del orden de 2.5±0.1 ps-1 (para 0.5 ML a 140K) y que es coherente con estudios recientes [2]. Por otro lado, una estimación de la fricción fonónica en el plano basal del grafito conduce a un valor de 0.02 ps-1 que es al menos dos órdenes de magnitud menor que los parámetros de fricción extraídos de los ajuste de datos. Concluimos que la interacción entre adsorbatos gobierna el comportamiento difusivo de las moléculas mientras que la interacción entre adsorbatos y substrato juega un papel secundario. Referencias: [1] R. Zacharia et al. Phys. Rev. B 69, 155406 (2004). [2] H. Hedgeland et al. Nature Phys. 5, 561 (2009)

Deep reinforcement learning for flow control exploits different physics for increasing Reynolds-number regimes

Deep artificial neural networks (ANNs) used together with deep reinforcement learning (DRL) are receiving growing attention due to their capabilities to control complex problems. This technique has been recently used to solve problems related to flow control. In this work, an ANN trained through a DRL agent is used to perform active flow control. Two-dimensional simulations of the flow around a cylinder are conducted and an active control based on two jets located on the walls of the cylinder is considered. By gathering information from the flow surrounding the cylinder, the ANN agent is able to learn effective control strategies for the jets, leading to a significant drag reduction. In the present work, a Reynolds-number range beyond those previously considered is studied and compared with results obtained using classical flow-control methods. Significantly different nature in the control strategies is identified by the DRL as the Reynolds number Re increases. For Re <= 1000 the classical control strategy based on an opposition control relative to the wake oscillation is obtained. For Re = 2000 the new strategy consists of an energisation of the boundary layers and the separation area, which modulate the flow separation and reduce drag in a fashion similar to that of the drag crisis, through a high frequency actuation. A cross-application of agents is performed for a flow at Re = 2000, obtaining similar results in terms of drag reduction with the agents trained at Re = 1000 and 2000. The fact that two different strategies yield the same performance make us question whether this Reynolds number regime (Re = 2000) belongs to a transition towards a nature-different flow which would only admit a high-frequency actuation strategy to obtain drag reduction. This finding allows the application of ANNs trained at lower Reynolds numbers but comparable in nature, saving computational resources.Comment: 26 pages, 5 figures, submitted to MDP

Risk Factors and Predictive Score for Bacteremic Biliary Tract Infections Due to Enterococcus faecalis and Enterococcus faecium: a Multicenter Cohort Study from the PROBAC Project

Biliary-tract bloodstream infections (BT-BSI) caused by Enterococcus faecalis and E. faecium are associated with inappropriate empirical treatment and worse outcomes compared to other etiologies. The objective of this study was to investigate the risk factors for enterococcal BT-BSI. Patients with BT-BSI from the PROBAC cohort, including consecutive patients with BSI in 26 Spanish hospitals between October 2016 and March 2017, were selected; episodes caused by E. faecalis or E. faecium and other causes were compared. Independent predictors for enterococci were identified by logistic regression, and a predictive score was developed. Eight hundred fifty episodes of BT-BSI were included; 73 (8.5%) were due to target Enterococcus spp. (48 [66%] were E. faecium and 25 [34%] E. faecalis). By multivariate analysis, the variables independently associated with Enterococcus spp. were (OR; 95% confidence interval): cholangiocarcinoma (4.48;1.32 to 15.25), hospital acquisition (3.58;2.11 to 6.07), use of carbapenems in the previous month (3.35;1.45 to 7.78), biliary prosthesis (2.19;1.24 to 3.90), and moderate or severe chronic kidney disease (1.55;1.07 to 2.26). The AUC of the model was 0.74 [95% CI0.67 to 0.80]. A score was developed, with 7, 6, 5, 4, and 2 points for these variables, respectively, with a negative predictive value of 95% for a score # 6. A model, including cholangiocarcinoma, biliary prosthesis, hospital acquisition, previous carbapenems, and chronic kidney disease showed moderate prediction ability for enterococcal BT-BSI. Although the score will need to be validated, this information may be useful for deciding empirical therapy in biliary tract infections when bacteremia is suspected. IMPORTANCE Biliary tract infections are frequent, and a significant cause of morbidity and mortality. Bacteremia is common in these infections, particularly in the elderly and patients with cancer. Inappropriate empirical treatment has been associated with increased risk of mortality in bacteremic cholangitis, and the probability of receiving inactive empirical treatment is higher in episodes caused by enterococci. This is because many of the antimicrobial agents recommended in guidelines for biliary tract infections lack activity against these organisms. To the best of our knowledge, this is the first study analyzing the predictive factors for enterococcal BT-BSI and deriving a predictive score.8 página

Risk Factors and Predictive Score for Bacteremic Biliary Tract Infections Due to Enterococcus faecalis and Enterococcus faecium: a Multicenter Cohort Study from the PROBAC Project

Biliary-tract bloodstream infections (BT-BSI) caused by Enterococcus faecalis and E. faecium are associated with inappropriate empirical treatment and worse outcomes compared to other etiologies. The objective of this study was to investigate the risk factors for enterococcal BT-BSI. Patients with BT-BSI from the PROBAC cohort, including consecutive patients with BSI in 26 Spanish hospitals between October 2016 and March 2017, were selected; episodes caused by E. faecalis or E. faecium and other causes were compared. Independent predictors for enterococci were identified by logistic regression, and a predictive score was developed. Eight hundred fifty episodes of BT-BSI were included; 73 (8.5%) were due to target Enterococcus spp. (48 [66%] were E. faecium and 25 [34%] E. faecalis). By multivariate analysis, the variables independently associated with Enterococcus spp. were (OR; 95% confidence interval): cholangiocarcinoma (4.48;1.32 to 15.25), hospital acquisition (3.58;2.11 to 6.07), use of carbapenems in the previous month (3.35;1.45 to 7.78), biliary prosthesis (2.19;1.24 to 3.90), and moderate or severe chronic kidney disease (1.55;1.07 to 2.26). The AUC of the model was 0.74 [95% CI0.67 to 0.80]. A score was developed, with 7, 6, 5, 4, and 2 points for these variables, respectively, with a negative predictive value of 95% for a score ? 6. A model, including cholangiocarcinoma, biliary prosthesis, hospital acquisition, previous carbapenems, and chronic kidney disease showed moderate prediction ability for enterococcal BT-BSI. Although the score will need to be validated, this information may be useful for deciding empirical therapy in biliary tract infections when bacteremia is suspected. IMPORTANCE Biliary tract infections are frequent, and a significant cause of morbidity and mortality. Bacteremia is common in these infections, particularly in the elderly and patients with cancer. Inappropriate empirical treatment has been associated with increased risk of mortality in bacteremic cholangitis, and the probability of receiving inactive empirical treatment is higher in episodes caused by enterococci. This is because many of the antimicrobial agents recommended in guidelines for biliary tract infections lack activity against these organisms. To the best of our knowledge, this is the first study analyzing the predictive factors for enterococcal BT-BSI and deriving a predictive score

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

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

Epidemiological trends of HIV/HCV coinfection in Spain, 2015-2019

Altres ajuts: Spanish AIDS Research Network; European Funding for Regional Development (FEDER).Objectives: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. Methods: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. Results: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). Conclusions: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p &lt; 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics