The O3N2 and N2 abundance indicators revisited: improved calibrations based on CALIFA and T e-based literature data

Astronomy and Astrophysics 559 (2013): A114 reproduced with permission from Astronomy and AstrophysicsThe use of integral field spectroscopy is since recently allowing to measure the emission line fluxes of an increasingly large number of star-forming galaxies, both locally and at high redshift. Many studies have used these fluxes to derive the gas-phase metallicity of the galaxies by applying the so-called strong-line methods. However, the metallicity indicators that these datasets use were empirically calibrated using few direct abundance data points (Te-based measurements). Furthermore, a precise determination of the prediction intervals of these indicators is commonly lacking in these calibrations. Such limitations might lead to systematic errors in determining the gas-phase metallicity, especially at high redshift, which might have a strong impact on our understanding of the chemical evolution of the Universe. The main goal of this study is to review the most widely used empirical oxygen calibrations, O3N2 and N2, by using newdirect abundance measurements. We pay special attention to (1) the expected uncertainty of these calibrations as a function of the index value or abundance derived and (2) the presence of possible systematic offsets. This is possible thanks to the analysis of the most ambitious compilation of Te-based H ii regions to date. This new dataset compiles the Te-based abundances of 603 H ii regions extracted from the literature but also includes new measurements from the CALIFA survey. Besides providing new and improved empirical calibrations for the gas abundance, we also present a comparison between our revisited calibrations with a total of 3423 additional CALIFA H ii complexes with abundances derived using the ONS calibration from the literature. The combined analysis of T e-based and ONS abundances allows us to derive their most accurate calibration to date for both the O3N2 and N2 single-ratio indicators, in terms of all statistical significance, quality, and coverage of the parameters space. In particular, we infer that these indicators show shallower abundance dependencies and statistically significant offsets compared to others'. The O3N2 and N2 indicators can be empirically applied to derive oxygen abundances calibrations from either direct abundance determinations with random errors of 0.18 and 0.16, respectively, or from indirect ones (but based on a large amount of data), reaching an average precision of 0.08 and 0.09 dex (random) and 0.02 and 0.08 dex (systematic; compared to the direct estimations), respectivelyR.A. Marino is funded by the Spanish program of International Campus of Excellence Moncloa (CEI). D. Mast thank the Plan Nacional de Investigación y Desarrollo funding programs, AYA2012-31935 of the Spanish Ministerio de Economía y Competitividad, for the support given to this project. S.F.S thanks the the Ramón y Cajal project RyC-2011-07590 of the spanish Ministerio de Economía y Competitividad, for the support giving to this project. F.F.R.O. acknowledges the Mexican National Council for Science and Technology (CONACYT) for financial support under the program Estancias Postdoctorales y Sabáticas al Extranjero para la Consolidación de Grupos de Investigación, 2010-2012. We acknowledge financial support for the ESTALLIDOS collaboration by the Spanish Ministerio de Ciencia e Innovación under grant AYA2010- 21887-C04-03. BG-L also acknowledges support from the Spanish Ministerio de Economía y Competitividad (MINECO) under grant AYA2012- 39408-C02-02. J.F.-B. acknowledges financial support from the Ramón y Cajal Program and grant AYA2010-21322-C03-02 from the Spanish Ministry of Economy and Competitiveness (MINECO), as well as to the DAGAL network from the People’s Program (Marie Curie Actions) of the European Union’s Seventh Framework Program FP7/2007-2013/ under REA grant agreement number PITN-GA-2011-289313. CK has been funded by project AYA2010-21887 from the Spanish PNAYA. P.P. acknowledges support by the Fundação para a Ciência e a Tecnologia (FCT) under project FCOMP-01-0124-FEDER-029170 (Reference FCT PTDC/FIS-AST/3214/2012), funded by FCT-MEC (PIDDAC) and FEDER (COMPETE). R.M.G.D. and R.G.B. also acknowledge support from the Spanish Ministerio de Economía y Competitividad (MINECO) under grant AyA2010-15081. V.S., L.G., and A.M.M. acknowledge financial support from the Fundação para a Ciência e a Tecnologia (FCT) under program Ciência 2008 and the research grant PTDC/CTE-AST/112582/200

Inter-Rater Variability in the Evaluation of Lung Ultrasound in Videos Acquired from COVID-19 Patients

12 páginas, 7 figuras, 1 tablaLung ultrasound (LUS) allows for the detection of a series of manifestations of COVID-19, such as B-lines and consolidations. The objective of this work was to study the inter-rater reliability (IRR) when detecting signs associated with COVID-19 in the LUS, as well as the performance of the test in a longitudinal or transverse orientation. Thirty-three physicians with advanced experience in LUS independently evaluated ultrasound videos previously acquired using the ULTRACOV system on 20 patients with confirmed COVID-19. For each patient, 24 videos of 3 s were acquired (using 12 positions with the probe in longitudinal and transverse orientations). The physicians had no information about the patients or other previous evaluations. The score assigned to each acquisition followed the convention applied in previous studies. A substantial IRR was found in the cases of normal LUS (κ = 0.74), with only a fair IRR for the presence of individual B-lines (κ = 0.36) and for confluent B-lines occupying 50% (κ = 0.50). No statistically significant differences between the longitudinal and transverse scans were found. The IRR for LUS of COVID-19 patients may benefit from more standardized clinical protocols.This research was partially funded by CDTI (Spanish acronym: Centre for Industrial Tech- nological Development), funding number COI-20201153. Partially supported by the Google Cloud Research Credits program with the funding number GCP19980904, by the project RTI2018-099118- A-I00 founded by MCIU/AEI/FEDER UE and by the European Commission–NextGenerationEU, through CSIC’s Global Health Platform (PTI Salud Global)

Effects of intubation timing in patients with COVID-19 throughout the four waves of the pandemic : a matched analysis

The primary aim of our study was to investigate the association between intubation timing and hospital mortality in critically ill patients with COVID-19-associated respiratory failure. We also analysed both the impact of such timing throughout the first four pandemic waves and the influence of prior non-invasive respiratory support on outcomes. This is a secondary analysis of a multicentre, observational and prospective cohort study that included all consecutive patients undergoing invasive mechanical ventilation due to COVID-19 from across 58 Spanish intensive care units (ICU) participating in the CIBERESUCICOVID project. The study period was between 29 February 2020 and 31 August 2021. Early intubation was defined as that occurring within the first 24 h of intensive care unit (ICU) admission. Propensity score (PS) matching was used to achieve balance across baseline variables between the early intubation cohort and those patients who were intubated after the first 24 h of ICU admission. Differences in outcomes between early and delayed intubation were also assessed. We performed sensitivity analyses to consider a different timepoint (48 h from ICU admission) for early and delayed intubation. Of the 2725 patients who received invasive mechanical ventilation, a total of 614 matched patients were included in the analysis (307 for each group). In the unmatched population, there were no differences in mortality between the early and delayed groups. After PS matching, patients with delayed intubation presented higher hospital mortality (27.3% versus 37.1%, p =0.01), ICU mortality (25.7% versus 36.1%, p=0.007) and 90-day mortality (30.9% versus 40.2%, p=0.02) when compared to the early intubation group. Very similar findings were observed when we used a 48-hour timepoint for early or delayed intubation. The use of early intubation decreased after the first wave of the pandemic (72%, 49%, 46% and 45% in the first, second, third and fourth wave, respectively; first versus second, third and fourth waves p<0.001). In both the main and sensitivity analyses, hospital mortality was lower in patients receiving high-flow nasal cannula (n=294) who were intubated earlier. The subgroup of patients undergoing NIV (n=214) before intubation showed higher mortality when delayed intubation was set as that occurring after 48 h from ICU admission, but not when after 24 h. In patients with COVID-19 requiring invasive mechanical ventilation, delayed intubation was associated with a higher risk of hospital mortality. The use of early intubation significantly decreased throughout the course of the pandemic. Benefits of such an approach occurred more notably in patients who had received high-flow nasal cannul

Prognostic implications of comorbidity patterns in critically ill COVID-19 patients: A multicenter, observational study

Background The clinical heterogeneity of COVID-19 suggests the existence of different phenotypes with prognostic implications. We aimed to analyze comorbidity patterns in critically ill COVID-19 patients and assess their impact on in-hospital outcomes, response to treatment and sequelae. Methods Multicenter prospective/retrospective observational study in intensive care units of 55 Spanish hospitals. 5866 PCR-confirmed COVID-19 patients had comorbidities recorded at hospital admission; clinical and biological parameters, in-hospital procedures and complications throughout the stay; and, clinical complications, persistent symptoms and sequelae at 3 and 6 months. Findings Latent class analysis identified 3 phenotypes using training and test subcohorts: low-morbidity (n=3385; 58%), younger and with few comorbidities; high-morbidity (n=2074; 35%), with high comorbid burden; and renal-morbidity (n=407; 7%), with chronic kidney disease (CKD), high comorbidity burden and the worst oxygenation profile. Renal-morbidity and high-morbidity had more in-hospital complications and higher mortality risk than low-morbidity (adjusted HR (95% CI): 1.57 (1.34-1.84) and 1.16 (1.05-1.28), respectively). Corticosteroids, but not tocilizumab, were associated with lower mortality risk (HR (95% CI) 0.76 (0.63-0.93)), especially in renal-morbidity and high-morbidity. Renal-morbidity and high-morbidity showed the worst lung function throughout the follow-up, with renal-morbidity having the highest risk of infectious complications (6%), emergency visits (29%) or hospital readmissions (14%) at 6 months (p<0.01). Interpretation Comorbidity-based phenotypes were identified and associated with different expression of in-hospital complications, mortality, treatment response, and sequelae, with CKD playing a major role. This could help clinicians in day-to-day decision making including the management of post-discharge COVID-19 sequelae. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

Peptidomic study of Spanish blue cheese (Valdeón) and changes after simulated gastrointestinal digestion

It is increasingly evident that digestion can affect the biological activity of cheese by the release of new active peptides from their precursors or, on the contrary, giving rise to fragments without activity. The characterization of the peptidome of a Spanish blue cheese, Valdeón, has been conducted before and after gastrointestinal digestion, and the digests have been compared to those obtained from pasteurized skimmed milk powder (SMP) using a bioinformatics platform. Peptidomic profiling of digests revealed several regions that are especially resistant to digestion (among them β-casein 60-93, 128-140, and 193-209). Some of them correspond to well-conserved regions between species (human, cow, sheep, and goat) and include peptide sequences with reported bioactivity. The great peptide homology found between both digests, cheese and SMP, suggests that the gastrointestinal digestion could bring closer the profile of products with different proteolytic state. Although most of the biologically active peptides found in cheese after digestion were also present in SMP digest, there were some exceptions that can be attributed to the absence of the relevant precursor peptide before digestion. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Funded by: Consolider-Ingenio FUN-C-Food CSD 2007-063. Grant Number: AGL2011-24643 and Ministerio de Economía y Competitividad. Grant Number: L021A12-2.Peer Reviewe

Aplicación de técnicas interactivas de aprendizaje en las sesiones de Tecnologías Industriales en el Grado de Ingeniería Biomédica de la Universidad de Alicante

La universidad afronta el reto de dar respuesta a las necesidades de formación de los profesionales de las próximas décadas. A pesar de las dificultades inherentes, este reto supone una magnífica oportunidad para la mejora de la formación universitaria a partir del cambio de modelo formativo que permita pasar de una formación basada en la enseñanza teórica o lección magistral a una formación orientada al desarrollo de competencias. En este contexto, se imparte la asignatura Tecnologías Industriales (33745), perteneciente al segundo curso del Grado en Ingeniería Biomédica durante el curso 2019/2020 y en esta asignatura se plantea el empleo de nuevas técnicas de docencia basadas en la preparación de preguntas acerca de los contenidos teóricos desarrollados en las sesiones de clase, que los alumnos podrán realizar simultáneamente con el empleo de una plataforma interactiva. Esta aplicación se clasifica dentro del aprendizaje móvil electrónico (M-learning) y de la gamificación, así como en Bring your own device, permitiendo al alumnado aprender por medio del juego pero no un contexto lúdico sino dentro del aula para que la experiencia de aprendizaje sea más motivadora. Así pues, se pretende extrapolar el uso de las experiencias similares y exitosas que se tiene constancia en el grado de Ingeniería Biomédica

Bioavailability and kinetics of the antihypertensive casein-derived peptide HLPLP in rats

The aim of this study was to investigate the oral bioavailability and kinetics of the milk casein-derived peptide HLPLP, which had previously demonstrated antihypertensive effect in spontaneously hypertensive rats. HLPLP disposition after single intravenous (4 mg/kg body weight) and oral (40 mg/kg body weight) doses was studied in rats. Plasma concentrations of HLPLP [β-casein fragment f(134-138)], and two derived fragments found after HLPLP administration, LPLP [β-casein fragment f(135-138)] and HLPL [β-casein fragment f(134-137)], were determined by ultrahigh performance liquid chromatography (UPLC) coupled on line to a Q-TOF instrument. For HLPLP, the elimination half-lives (T1/2β) were 7.95 min after intravenous and 11.7 min after oral administration. The volume of distribution at steady state (Vss = 30.8 L/kg) suggests a considerable uptake of HLPLP into tissues. HLPLP was converted to the peptides LPLP and HLPL. After HLPLP intravenous administration, the elimination half-lives (T1/2β) for these biotransformed peptides, LPLP and HLPL, were 8.38 and 10.9 min, respectively. After oral administration, HLPLP was rapidly absorbed with an absorption half-life (T1/2a) of 2.79 min. The oral bioavailability of HLPLP was found to be 5.18%. Our study suggested that HLPLP was rapidly absorbed and eliminated after oral administration, biotransformed into smaller fragments LPLP and HLPL, and distributed throughout the body by the circulation blood. The present pharmacokinetic information from a preclinical kinetic study in rats can also play an important role in designing future kinetic studies in humans for assessing HLPLP dose-response relationship.This work was supported by projects Consolider-Ingenio FUNC-Food CSD 2007-063, FP7-SME-2012-315349 (FOFIND), and AGL2011-24643 from Ministerio de Economiá y Competitividad, projects P2009/AGR-1469 and (ALIBIRDCM) S2013/ABI-2728 from Comunidad de Madrid, and project 920204 UCM-BSCH from Universidad Complutense de Madrid.Peer Reviewe

Comparison of peptidomic studies of simulated gastrointestinal digests from Spanish cheeses

Resumen del póster presentado al 1st International Conference on Food Digestion celebrado en Cesena (Italia) del 19 al 21 de marzo de 2012.During cheese ripening, casein is hydrolyzed into a large variety of peptides by proteases and peptidases from milk, rennet, starter culture and secondary microbial flora. These peptides are characteristic of each cheese type and ripening time and are in part responsible of the typical and differentiating organoleptic characteristics of cheese. Some of these peptides are known to be partially resistant to digestion or they can act as precursors of the peptides that finally are absorbed. Different studies performed at our laboratory aimed the identification of the major peptides generated after two-step hydrolysis process that simulates gastrointestinal digestion of different Spanish cheeses. These include: Manchego cheese which is a hard or semi-hard variety made from ewe's milk; Serena cheese which is elaborated with ewe's milk and vegetal rennet; Tetilla cheese is made from bovine milk and animal rennet and a cheeses made from mixtures of caprine, ovine and bovine milk (Iberian and Valdeon cheeses). Therefore, the degree of proteolysis and the peptidic profile before simulated digestion was different and distinctive for each cheese type and ripening time. After digestion, the water soluble extracts were subjected to ultrafiltration through a 3000 Da membrane and the permeates were analyzed by HPLC coupled to tandem spectrometry. Many homologous sequences were found in the ultrafiltrates of the water soluble extracts although they were obtained from different cheese types. There are casein regions specially resistant to hydrolysis that were found in many of these studies such as, k¿-casein f(134-139) HLPLPL; k-casein f(47-52) DKIHPF; k-casein f(114-119) YPVEPF. Interestingly, some of the most often peptides found had been previously been reported with a given bioactivity as antihypertensive, opioid or with antiallergenic properties.Peer Reviewe

Ultrafast particle size reduction of Fe73.9Si15.5Cu1Nb3B6.6 by high-energy milling: Nb2O5 as a marker of permeability enhancement and magnetic hardening

[EN] This work is conceived to provide a reproducible and fast method to obtain optimal particle sizes for competitive ultrasoft magnetic applications based on FeSiCuNbB-nanostructured particles. In this scenario, partial nanocrystallization of the α-FeSi compound is promoted by annealing and subsequent high-energy ball milling processes. The milling is performed in this material, for the first time, by a combination of mixer, vibratory, and planetary ball milling motions. Under these conditions, structural and magnetic properties are tuned as a function of milling time with reduced particle size distributions and maintaining the ultrasoft magnetic character. In addition, drastic electronic and structural changes are observed after a few minutes of milling where saturation magnetization and initial permeability are strongly influenced by the percentage of the α-FeSi nanocrystallites formed. Above 30 min of ball milling, the formation of a low concentration of NbO clusters is detected by confocal Raman microscopy. This identification is essential because the rejection of Nb from the amorphous matrix rich in Fe−Nb−B atoms acts as a marker of the seed mechanism that causes the deterioration of the softness character of these nanostructures. Therefore, on the one hand, this work introduces a successful procedure by combined milling processes to optimize the saturation magnetization and permeability with submicron particle sizes and, on the other hand, the detection of NbO clusters is implemented as an influential marker on the magnetic properties of these soft nanostructured particles.The authors acknowledge the Spanish Ministry of Industry, Economy, and Competitiveness for financing the project MAT2015-65445-C2-1-R, MAT2017-86450-C4-1-R, MAT2015-67557-C2-1-P, the Comunidad de Madrid by S2013/MIT-2850 NANOFRONTMAG, and the European Commission under H2020 frame by AMPHIBIAN project ID: 720853. The authors are also grateful for the financial support from the Spanish Ministry of Science, Innovation and Universities (MICIU) and The Spanish National Research Council (CSIC) under Grant no. PIE 2010-6OE-013. A.S. acknowledges the financial support from the Comunidad de Madrid for an “Atracción de Talento Investigador” contract (no. 2017-t2/IND5395). C.G.-M. and A.Q. acknowledges the financial support from MICINN through the “Juan de la Cierva” Program (FJC2018-035532-I) and through the Ramón y Cajal Contract RYC-2017-23320.Peer reviewe