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Using the IMK–IAA data processor, methane and nitrous oxide distributions were retrieved from version-8 limb emission spectra recorded with the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS). The dataset includes measurements from the nominal, upper troposphere–lower stratosphere, middle-atmosphere, upper-atmosphere and noctilucent-cloud observation modes. The processing differs from the previous version-5 data with respect to the atmospheric state variables that are jointly retrieved along with the target gases CH4 and N2O, the treatment of the radiance offset, the selection of microwindows, the regularization, the spectroscopic data used and the treatment of horizontal variability of the atmospheric state. Besides the regular data product, a coarse-grid representation of the profiles with unity averaging kernels is available, as well as a specific research product for middle-atmosphere measurements resulting from a slightly different retrieval approach. The CH4 errors are dominated by the large spectroscopic uncertainty for line intensities, which probably is too pessimistic, and estimated to be 21 %–34 % in the altitude range 6–68 km for northern midlatitude summer day conditions. The N2O errors are 7 %–17 % below 45 km. At higher altitudes they increase strongly due to nearly vanishing N2O amounts. Analysis of the horizontal averaging kernels reveals that for both gases the horizontal resolution is sampling-limited; i.e., information is not smeared over consecutive limb scans. Zonal-mean seasonal composites of both CH4 and N2O exhibit the typical distribution of source gases with strong upwelling in the tropics and subsidence above the winter poles. Comparison with the previous data version shows several improvements: first, the vertical resolution of the retrieved CH4 (N2O) profiles has generally been significantly enhanced and varies between 2.5 (2.5) and 4 (5) km at altitudes between 10 and 60 km, with the best resolution around 30 km for both species. Secondly, the number of non-converged retrievals has been clearly reduced, and thirdly, formerly strongly oscillating profiles are now considerably smoother.

The Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) on Envisat provided infrared limb emission spectra, which were used to infer global distributions of CFC-11, CFC-12, and HCFC-22. Spectra were analysed using constrained non-linear least-squares fitting. Changes with respect to earlier data versions refer to the use of version 8 spectra, the altitude range where the background continuum is considered, details of the regularization and microwindow selection, and the occasional joint fitting of interfering species, the use of new spectroscopic data, the joint fit of a tangent-height-dependent spectral offset, and the use of 2D temperature fields. In the lower stratosphere the error budget is dominated by uncertainties in spectroscopic data, while above this measurement noise is the leading error source. The vertical resolution of CFC-11 and CFC-12 is 2–3 km near the tropopause, about 4 km at 30 km altitude, and 6–10 km at 50 km. The vertical resolution of HCFC-22 is somewhat coarser, 3–4 km at the tropopause and 10–12 km at 35 km altitude. In the altitude range of interest, the horizontal resolution is typically limited by the horizontal sampling of the measurements, not by the smearing of the retrievals. Horizontal information displacement does not exceed 150 km, which can become an issue only for comparisons with model simulations with high horizontal resolution or localized in situ observations. Along with the regular data product, an alternative representation of the data on a coarser vertical grid is offered. These data can be used without consideration of the averaging kernels. The new data version provides improvement with respect to reduction of biases and improved consistency between the full- and reduced-resolution mission period of MIPAS.

Introduction: Data on positive rechallenge in idiosyncratic drug-induced liver injury (DILI) are scarce. We aim to analyse the clinical presentation, outcome and drugs associated with positive rechallenge in two DILI registries. Methods: Cases from the Spanish and Latin American DILI registries were included. Demographics, clinical characteristics and outcome of cases with positive rechallenge according to CIOMS/RUCAM and current definitions were analysed. Results: Of 1418 patients with idiosyncratic DILI, 58 cases had positive rechallenge (4.1%). Patients with positive rechallenge had shorter duration of therapy (p=0.001) and latency (p=0.003). In patients with rechallenge, aspartate transaminase levels were increased (p=0.026) and showed a prolonged time to recovery (p=0.020), albeit no differences were seen in terms of fatal outcomes. The main drug implicated in rechallenge was amoxicillin-clavulanate (17%). The majority of re-exposure events were unintentional (71%). Using both existing definitions of positive rechallenge, there were four cases which exclusively fulfilled the current criteria and five which only meet the historical definition. All cases of positive rechallenge, irrespective of the pattern of damage, fulfilled the criteria of either alanine transaminase (ALT) ≥3 times the upper limit of normal (ULN) and/or alkaline phosphatase (ALP) ≥2 times ULN. Conclusions: Episodes of rechallenge were characterised by shorter duration of therapy and latency, and longer time to resolution, but did not show an increased incidence of fatal outcome. Based on our findings, ALT ≥3 times ULN and/or ALP ≥2 times ULN, regardless of the pattern of damage, is proposed as a new definition of rechallenge in DILI.

A modified self-propagating high-temperature synthesis in bath (SHSB) via cast was successfully used to produce the aluminium-based composites reinforced by TiC and (Ti,W)C nanoparticles. The process was managed by the addition of a moderator affecting supercooling, which consequently influences the nucleation and growth of TiC crystals. Thus, by choosing the suitable amount of moderator, not only the size and amount but also the distribution of the strengthening particles can be controlled. In this work, the research was performed in a twin-track approach: fabrication of good quality TiC particles with a homogenous distribution inside of the aluminium matrix (1), and modification of TiC particles by the addition of W in order to improve the coherency degree between both particles and the matrix and ensure more uniform distribution of the reinforcement (2). Moreover, the homogenous microstructure of Al/TiC composites was obtained. TiC particles were uniformly distributed, and no cluster in the matrix in composite up to the highest moderator content (80 wt%) was found. The compressive strength and hardness of composites reinforced with TiC particles have been significantly improved (over 100 %) compared to the base alloy while the highest values were achieved for the composite containing 80 wt% of the moderator. Moreover, the addition of W causes a significant change in the lattice parameters of TiC at the interface without changing its face-centered cubic structure (fcc). This in turn leads to improved coherence at the particle/matrix interface.

Abstract Background The term sepsis refers to a complex and heterogeneous syndrome. Although great progress has been made in improving the diagnosis and treatment of this condition, it continues to have a huge impact on morbidity and mortality worldwide. Mesenchymal stem cells are a population of multipotent cells that have immunomodulatory properties, anti-apoptotic effects, and antimicrobial activity. We studied these capacities in a porcine model of peritoneal sepsis. Methods We infused human adipose-derived mesenchymal stem cells (ADSCs) into a porcine model of peritoneal sepsis. Twenty piglets were treated with antibiotics alone (control group) or antibiotics plus peritoneal infusion of ADSCs at a concentration of 2 × 106 cells/kg or 4 × 106 cells/kg (low- and high-dose experimental groups, respectively). The animals were evaluated at different time points to determine their clinical status, biochemical and hematologic parameters, presence of inflammatory cytokines and chemokines in blood and peritoneal fluid, and finally by histologic analysis of the organs of the peritoneal cavity. Results One day after sepsis induction, all animals presented peritonitis with bacterial infection as well as elevated C-reactive protein, haptoglobin, IL-1Ra, IL-6, and IL-1b. Xenogeneic ADSC infusion did not elicit an immune response, and peritoneal administration of the treatment was safe and feasible. One day after infusion, the two experimental groups showed a superior physical condition (e.g., mobility, feeding) and a significant increase of IL-10 and TGF-β in blood and a decrease of IL-1Ra, IL-1b, and IL-6. After 7 days, all animals treated with ADSCs had better results concerning blood biomarkers, and histopathological analysis revealed a lower degree of inflammatory cell infiltration of the organs of the peritoneal cavity. Conclusions Intraperitoneal administration of ADSCs as an adjuvant therapy for sepsis improves the outcome and diminishes the effects of peritonitis and associated organ damage by regulating the immune system and reducing intra-abdominal adhesions in a clinically relevant porcine model of abdominal sepsis.

Motivated by an improved European Space Agency (ESA) version of calibrated Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) spectra (version 8.03), we have released version 8 of MIPAS temperatures and pointing information retrieved from 2005–2012 MIPAS measurements at 12–15 µm in the Middle Atmosphere (MA), Upper Atmosphere (UA) and Noctilucent Cloud (NLC) measurement modes. The Institute of Meteorology and Climate Research–Instituto de Astrofisica de Andalucia (IMK–IAA) retrieval processor in use considers non-local thermodynamic equilibrium (non-LTE) emission explicitly for each limb scan. This non-LTE treatment is essential to obtain accurate temperatures above the mid-mesosphere because at the altitudes covered, up to 115 km, the simplified climatology-based non-LTE treatment employed for the Nominal (NOM) measurements is insufficient. Other updates in MA/UA/NLC version 8 non-LTE temperature retrievals from previous data releases include more realistic atomic oxygen and carbon dioxide abundances, an updated set of spectroscopic data, an improved spectral shift retrieval, a continuum retrieval extended to altitudes up to 58 km, consideration of an altitude-dependent radiance offset retrieval, the use of wider microwindows above 85 km to capture the offset, an improved accuracy in forward model calculations, new a priori temperature information, improved temperature horizontal gradient retrievals and the use of MIPAS version 5 interfering species where available. The resulting MIPAS MA/UA/NLC IMK–IAA temperature dataset is reliable for scientific analysis in the full measurement vertical range for the MA (18–102 km) and the NLC (39–102 km) observations and from 42 to 115 km for the UA observations. The random temperature errors, dominated by the instrumental noise, are typically less than 1 K below 60 km, 1–3 K at 60–70 km, 3–5 K at 70–90 km, 6–8 K at 90–100 km, 8–12 K at 100–105 km and 12–20 K at 105–115 km. Random pointing correction errors, also mainly arising from instrumental noise, are on average 50 m for tangent altitudes up to 60 km and decrease linearly to values smaller than 20 m for altitudes above 95 km. The vertical resolution is 3 km at altitudes below 50 km, 3–5 km at 50–70 km, 4–6 km at 70–90 km, 6–10 km at 90–100 km and 8–11 km at 100–115 km. The systematic errors in retrieved temperatures below 75 km are driven by uncertainties in the CO2 spectroscopic data and, above 80 km, by uncertainties in the non-LTE model parameters (including collisional rates and atomic oxygen abundance) and the CO2 abundance. These lead to systematic temperature errors of less than 0.7 K below 55 km, 1 K at 60–80 km, 1–2 K at 80–90 km, 3 K at 95 km, 6–8 K at 100 km, 10–20 K at 105 km and 20–30 K at 115 km. Systematic errors in the tangent altitude correction, mainly arising from CO2 spectroscopic uncertainties, are 250 m at 20 km, 200 m at 40–60 km, 100 m at 80 km and smaller than 50 m above 90 km. The consistency between the MA/UA/NLC and the NOM IMK–IAA datasets is excellent below 70 km (typical 0.5–1 K differences). The comparison of this temperature dataset with co-located Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) temperature measurements shows excellent agreement, with differences typically within 1.5 K below 90 km, 1–3 K at 90–95 km, 1–5 K at 95–100 km, 1–8 K at 100–105 km and 1–10 K above. The agreement with SABER improves with respect to previous MIPAS IMK–IAA data versions.

We present a new version of O3 data retrieved from the three Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) observation modes that we refer to for simplicity as the modes of the middle atmosphere (middle atmosphere, MA; upper atmosphere, UA; and noctilucent cloud, NLC). The O3 profiles cover altitudes from 20 up to 100 km for the daytime and up to 105 km at nighttime, for all latitudes, and the period 2005 until 2012. The data have been obtained with the IMK–IAA (Institute of Meteorology and Climate Research and Instituto de Astrofísica de Andalucía) MIPAS level-2 data processor and are based on ESA version-8 re-calibrated radiance spectra with improved temporal stability. The processing included several improvements with respect to the previous version, such as the consistency of the microwindows and spectroscopic data with those used in the nominal-mode V8R data, the O3 a priori profiles, and updates of the non-local thermodynamic equilibrium (non-LTE) parameters and the nighttime atomic oxygen. In particular, the collisional relaxation of O3(v1,v3) by the atomic oxygen was reduced by a factor of 2 in order to obtain a better agreement of nighttime mesospheric O3 with “non-LTE-free” measurements. Random errors are dominated by the measurement noise with 1σ values for single profiles for the daytime of < 5 % below ∼ 60 km, 5 %–10 % between 60 and 70 km, 10 %–20 % at 70–90 km, and about 30 % at 95 km. For nighttime, they are very similar below 70 km but smaller above (10 %–20 % at 75–95 km, 20 %–30 % at 95–100 km and larger than 30 % above 100 km). The systematic error is ∼ 6 % below ∼ 60 km (dominated by uncertainties in spectroscopic data) and 8 %–12 % above ∼ 60 km, mainly caused by non-LTE uncertainties. The systematic errors in the 80–100 km range are significantly smaller than in the previous version. The major differences with respect to the previous version are as follows: (1) the new retrievals provide O3 abundances in the 20–50 km altitude range that are larger by about 2 %–5 % (0.2–0.5 ppmv); (2) O3 abundances were reduced by ∼ 2 %–4 % between 50 and 60 km in the tropics and mid-latitudes; (3) O3 abundances in the nighttime O3 minimum just below 80 km were reduced, leading to a more realistic diurnal variation; (4) daytime O3 concentrations in the secondary maximum at the tropical and middle latitudes (∼ 40 %, 0.2–0.3 ppmv) were larger; and (5) nighttime O3 abundances in the secondary maximum were reduced by 10 %–30 %. The O3 profiles retrieved from the nominal mode (NOM) and the middle-atmosphere modes are fully consistent in their common altitude range (20–70 km). Only at 60–70 km does daytime O3 of NOM seem to be larger than that of MA/UA by 2 %–10 %. Compared to other satellite instruments, MIPAS seems to have a positive bias of 5 %–8 % below 70 km. Noticeably, the new version of MIPAS data agrees much better than before with all instruments in the upper mesosphere–lower thermosphere, reducing the differences from ∼± 20 % to ∼± 10 %. Further, the diurnal variation in O3 in the upper mesosphere (near 80 km) has been significantly improved.

Actinotignum schaalii affects elderly people and is associated with individuals with urological-related predispositions, but can be found in a variety of locations, such as cutaneous, intraabdominal, genitourinary and surgical infections. Disseminated infections occur less frequently and are by and large related to urinary tract colonisation.This pathogen is often neglected due to growth requirements, especially in urinary tract infections. We present 107 Actinotignum schaalii isolated from genitourinary samples (80.4%), from skin and soft tissue infections (13.1%), from bone and deep tissue infection (4.7%) and from blood cultures (1.9%). The automated system Alfred 60/AST was paramount for the isolation of 77.6% of the UTI.All the isolates tested were susceptible to penicillin, ampicillin, linezolid, vancomycin, teicoplanin, rifampicin and tetracycline.In conclusion, we present a large series of Actinotignum schaalii infections. This pathogen is hard to isolate, and is resistant to commonly used empirical antimicrobials.

The use of magnetic fields as external stimuli to improve the kinetics of electrochemical reactions is attracting substantial attention, given their potential to reduce energy losses. Despite recent reports showing a positive effect on catalytic performance upon applying a magnetic field to a working electrode, there are still many uncertainties and a lack of experimental evidence correlating the presence of the magnetic field to the electrocatalytic performance. Here, we present a combination of electrochemical and spectroscopic tools that demonstrate how the presence of an external magnetic field alters the reaction mechanism of the electrocatalytic oxygen evolution reaction (OER), accelerating the overall performance of a Ni4FeOx electrode. Complementary experimental evidence has been gathered supporting the participation of this microscopic magnetic field effect. Electrochemical impedance spectroscopy (EIS) points to a speed-up of the intrinsic reaction kinetics, independent of other indirect effects. In the same direction, the spectro-electrochemical fingerprint of the intermediate species that appear during the electrocatalytic cycle, as detected under operando conditions, indicates a change in the order of the reaction as a function of hole accumulation. All these experimental data confirm the direct influence of an external magnetic field on the reaction mechanism at the origin of the magnetically enhanced electrocatalytic OER.

Atenolol (ATL) is a beta-blocker pharmaceutical product which is excreted mainly unchanged and may represent a long-term risk for organisms present in the sea and in fresh water. Due to its low biodegradation rate, electrochemical advanced oxidation processes (EAOPs) can be used to remove this compound. In this work, ATL ecotoxicity was analyzed in the presence of sodium sulfate (Na2SO4), which is widely used as supporting electrolyte in EAOPs. Ecotoxicity values were expressed as the pollutant concentration that leads to a 50% inhibition of the root elongation of Lactuca sativa seeds in relation to the control (EC50(5 days)). The obtained values for ATL showed an EC50(5 days) of 1377 mg L−1 towards Lactuca sativa. When Na2SO4 was added, the toxicity of the sample increased but no synergy was detected between both compounds. With 2 g L−1 Na2SO4, ATL showed an EC50(5 days) of 972 mg L−1; and with 4 g L−1 Na2SO4 and higher concentrations, EC50 value for ATL was 0 mg L−1. Statistical tools were used to obtain the zones of the [ATL]-[Na2SO4] plane which are toxic towards Lactuca sativa.Solutions containing ATL and Na2SO4 were treated by electrooxidation. Two anode materials (a boron-doped diamond electrode and a microporous Sb-doped SnO2 ceramic one); three operation currents (0.4, 0.6 and 1 A); and two reactor configurations (one-compartment reactor and two-compartment reactor separated by a cation exchange membrane) were used. Lactuca sativa seeds and Vibrio fischeri bacterium tests were employed to evaluate the toxicity of the solutions before and after applying the electrooxidation process. In all the tests, the ecotoxicity of the treated sample increased. This fact is owing to the persulfate presence in the solution due to the sulfate electrochemical oxidation. Nevertheless, none of the final samples were toxic towards Vibrio fischeri because ecotoxicity values were lower than 10 TU; and, in the case of the one-compartment reactor, practically all of them were also non-toxic towards Lactuca sativa. The toxicity of the treated samples increased when using the two-compartment reactor in the presence of the BDD anode, and when the operation current was increased. This is attributed to the highest formation of persulfates. Amongst all the tests performed in this work, the lowest toxicity value (i.e., 3 TU) together with the complete mineralization and degradation degrees was achieved with the two-compartment reactor using the BDD anode and operating at 0.6 A.

IntroductionParents of children with neuromuscular diseases experience multiple difficulties in their daily lives that affect their physical and psychological health. The risk factors for these health issues have not been sufficiently investigated. Therefore, the aim of this study was to analyze the potential predictors of overload in these parents, including QoL, somatic symptomatology, life satisfaction, psychological adjustment and certain sociodemographic variables.MethodsA cross-sectional research study was conducted among parents who are caregivers for children with NMD in Spain. A convenience sample of 110 parents who were contacted by associations and hospitals was used. Variables were evaluated using the sociodemographic questionnaire, CarerQol-7D, PHQ-15, Barthel Index, Psychological Adaptation Scale, Zarit Overload Scale and Satisfaction with Life Scale.ResultsOne of the most relevant findings of the present study is the identification of 3 overload groups (mild to moderate, moderate to severe, and severe overload) based on life satisfaction and somatic symptom scores within the predictive model of the discriminate analysis. Wilk’s lambda of the discriminant function was 0.568, χ2 (2, n = 55) = 8.815, p

Satellite data records of stratospheric water vapour have been compared to balloon-borne frost point hygrometer (FP) profiles that are coincident in space and time. The satellite data records of 15 different instruments cover water vapour data available from January 2000 through December 2016. The hygrometer data are from 27 stations all over the world in the same period. For the comparison, real or constructed averaging kernels have been applied to the hygrometer profiles to adjust them to the measurement characteristics of the satellite instruments. For bias evaluation, we have compared satellite profiles averaged over the available temporal coverage to the means of coincident FP profiles for individual stations. For drift determinations, we analysed time series of relative differences between spatiotemporally coincident satellite and hygrometer profiles at individual stations. In a synopsis we have also calculated the mean biases and drifts (and their respective uncertainties) for each satellite record over all applicable hygrometer stations in three altitude ranges (10–30 hPa, 30–100 hPa, and 100 hPa to tropopause). Most of the satellite data have biases % and average drifts % yr−1 in at least one of the respective altitude ranges. Virtually all biases are significant in the sense that their uncertainty range in terms of twice the standard error of the mean does not include zero. Statistically significant drifts (95 % confidence) are detected for 35 % of the ≈ 1200 time series of relative differences between satellites and hygrometers.

Resumen: Introducción: La aplicación de la inteligencia artificial y en particular de algoritmos de aprendizaje automático o «machine learning» (ML) constituye un desafío y al mismo tiempo una gran oportunidad en diversas disciplinas científicas, técnicas y clínicas. Las aplicaciones específicas en el estudio de la esclerosis múltiple (EM) no han sido una excepción mostrando un creciente interés en los últimos años. Objetivo: Realizar una revisión sistemática de la aplicación de algoritmos de ML en la EM. Material y métodos: Empleando el motor de búsqueda de libre acceso PubMed que accede a la base de datos MEDLINE, se seleccionaron aquellos estudios que incluyeran simultáneamente los dos siguientes conceptos de búsqueda: «machine learning» y «multiple sclerosis». Se rechazaron aquellos estudios que fueran revisiones, estuvieran en otro idioma que no fuera el castellano o el inglés, y aquellos trabajos que tuvieran un carácter técnico y no fueran aplicados para la EM. Se seleccionaron como válidos 76 artículos y fueron rechazados 38. Conclusiones: Tras la revisión de los estudios seleccionados, se pudo observar que la aplicación del ML en la EM se concentró en cuatro categorías: 1) clasificación de subtipos de pacientes dentro de la enfermedad; 2) diagnóstico del paciente frente a controles sanos u otras enfermedades; 3) predicción de la evolución o de la respuesta a intervenciones terapéuticas y por último 4) otros enfoques. Los resultados hallados hasta la fecha muestran que los diferentes algoritmos de ML pueden ser un gran apoyo para el profesional sanitario tanto en la clínica como en la investigación de la EM. Abstract: Introduction: The applications of artificial intelligence, and in particular automatic learning or “machine learning” (ML), constitute both a challenge and a great opportunity in numerous scientific, technical, and clinical disciplines. Specific applications in the study of multiple sclerosis (MS) have been no exception, and constitute an area of increasing interest in recent years. Objective: We present a systematic review of the application of ML algorithms in MS. Materials and methods: We used the PubMed search engine, which allows free access to the MEDLINE medical database, to identify studies including the keywords “machine learning” and “multiple sclerosis.” We excluded review articles, studies written in languages other than English or Spanish, and studies that were mainly technical and did not specifically apply to MS. The final selection included 76 articles, and 38 were rejected. Conclusions: After the review process, we established 4 main applications of ML in MS: 1) classifying MS subtypes; 2) distinguishing patients with MS from healthy controls and individuals with other diseases; 3) predicting progression and response to therapeutic interventions; and 4) other applications. Results found to date have shown that ML algorithms may offer great support for health professionals both in clinical settings and in research into MS.

Abstract We report on outstanding photo-responsivity, R > 103 A/W, fast response (~0.1 s), and broadband sensitivity ranging from the UV to the NIR in two terminal graphene/MoS2 photodetectors. Our devices are based on the deterministic transfer of MoS2 on top of directly grown graphene on sapphire, and their performance outperforms previous similar photodetectors using large-scale grown graphene. Here we devise a protocol for the direct growth of transparent (transmittance, Tr > 90%), highly conductive (sheet resistance, R □

Introduction: Little is known about the clinical characteristics of women at increased risk for abnormal uterine bleeding (UB) during anticoagulation for venous thromboembolism (VTE). Methods: We used the RIETE registry to identify the baseline characteristics of women developing abnormal UB during anticoagulation. We used logistic regression analysis to identify independent predictors for abnormal UB. Then, we built a prognostic score to identify at-risk women. Results: From March 2001 through October 2022, there were 54,372 women with VTE. During anticoagulation (median, 181 days), 318 (0.6%) developed abnormal UB (major bleeding = 88, clinically relevant non-major (CRNM) = 230). On multivariable analysis, women aged 70 kg, with uterine cancer, recent UB, anemia, estrogen-related VTE, or receiving rivaroxaban or apixaban were at increased risk for abnormal UB. Using the prognostic score, 42,273 women (78%) were at low-risk, 8,828 (16%) intermediate-, and 3,271 (6.1%) at high-risk for abnormal UB. Their rates of abnormal UB were: 0.28 (95%CI: 0.23–0.35), 1.32 (95%CI: 1.07–1.61) and 7.12 (95%CI: 5.98–8.41) bleeds per 100 patient-years, respectively. The c-statistic was 0.80 (95%CI: 0.77–0.83). The rates of major UB were: 0.06 (95%CI: 0.04–0.09), 0.43 (95%CI: 0.30–0.60) and 1.85 (95%CI: 1.31–2.53) per 100 patient-years, respectively (c-statistic: 0.84; 95%CI: 0.80–0.89). The rates of CRNM uterine bleeding were: 0.21 (95%CI: 0.17–0.26), 0.85 (95%CI: 0.65–1.08), and 5.02 (95%CI: 4.09–6.10) bleeds per 100 patient-years, respectively (c-statistic: 0.78; 95%CI: 0.75–0.82). Conclusions: Using 7 variables easily available at admission, we built a prognostic score that reliably identified women with VTE at increased risk for abnormal UB during anticoagulation.

A novel method for obtaining ceramic (tricalcium phosphate, TCP) fibres with a small diameter (below 0.1 mm) is proposed and its potential use in the 3D printing of scaffolds for biomedical applications is explored. An ink consisting of a high solid content (40 vol%) ceramic slurry in a photocurable resin was prepared and extruded using near-field electrospinning. The influence of the electric potential, flow rate, and distance between tip and collector on the fabrication process in static mode were studied and the role played by unidirectional motion of the collector was also analyzed. A one order of magnitude reduction in the diameter of the jet to around 30 μm is demonstrated under static conditions, which increased to around 100 μm when collector was displaced. Continuous fibres were deposited but the slurry spread over the collector. The method was implemented on a DIW system, using in-flight UV light curing to prevent the spreading of the ink upon deposition. The feasibility of the strategy was demonstrated, although challenges remain for the optimization and control of the fabrication process. Nevertheless, these preliminary results suggest this could be a promising alternative to produce 3D ceramic scaffolds for biomedical applications with improved spatial resolution. Resumen: Se propone un nuevo método para la obtención de fibras cerámicas (fosfato tricálcico, TCP) de pequeño diámetro (menos de 0.1 mm) y se explora su potencial uso en la impresión 3D de andamiajes para aplicaciones biomédicas. Suspensiones cerámicas de alto contenido sólido (40 vol%) en una resina fotocurable fueron extruidas mediante electrohilado de campo cercano, analizando la influencia del potencial eléctrico, el caudal y la distancia entre la punta y el colector y el movimiento de este en el diámetro de la fibra. Se demuestra una reducción de un orden de magnitud en el diámetro del chorro hasta ∼30 μm en estático y hasta ∼100 μm con el colector en movimiento. Se depositaron fibras continuas, pero se observó esparcimiento de la suspensión sobre el colector. El método se implementó en un sistema de moldeo robotizado, utilizando curado en vuelo por luz ultravioleta para evitar el esparcimiento de la tinta tras la deposición. Aunque la viabilidad de la estrategia queda demostrada, siguen existiendo retos para la optimización y control del proceso de fabricación. No obstante, estos resultados preliminares indican que esta técnica podría ser una alternativa prometedora para producir andamios cerámicos 3D para aplicaciones biomédicas con una resolución espacial mejorada.

AbstractSympatric distribution and syntopy are not common in closely related species since sporadic crosses may lead to the formation of hybrid zones disrupting the differentiation of sympatric incipient species. In Central Spain two morphologically similar species of Mediimorda Méquignon, 1946, M. batteni Plaza-Infante, 1985 and M. bipunctata (Germar, 1827) are strictly sympatric. Mediimorda batteni is endemic to the Iberian Peninsula while M. bipunctata is widely distributed in the Western Palaearctic Region. Intriguingly, sympatric distribution among closely related taxa that exhibits little morphological variation is not common. This makes us wonder if we are really facing two independent evolutionary units of Mediimorda as previously proposed or just two phenotypic morphs of a single taxon. To test for this hypothesis, we performed Bayesian and phylogeographic analyses based on mitochondrial (cox1) and nuclear (ITS2) data and estimated divergence time of clades. Additionally, a morphological revision and construction of potential distribution models were included to determine possible niche differences. Our results corroborate the existence of two lineages well differentiated, that probably diverged during the Pliocene. According to the morphology, each clade corresponds to the previously recognized M. batteni and M. bipunctata. The absence of hybridization and ecological segregation suggests that sympatric and syntopic distribution was accomplished long time after the speciation event that separated the two taxa took place. We propose that the divergence between clades was originated by allopatric speciation during the Late Pliocene subsequently followed by range shifts during the Pleistocene climatic oscillations, which resulted in the current syntopy of the two taxa.

New global nitric oxide (NO) volume mixing ratio and lower-thermospheric temperature data products, retrieved from Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) spectra with the Institute of Meteorology and Climate Research and Instituto de Astrofísica de Andalucía (IMK-IAA) MIPAS data processor, have been released. The dataset covers the entire Envisat mission lifetime and includes retrieval results from all MIPAS observation modes. The data are based on European Space Agency (ESA) version 8 calibration and were processed using an improved retrieval approach compared to previous versions, specifically regarding the choice and construction of the a priori and atmospheric parameter profiles, the treatment of horizontal inhomogeneities, the treatment of the radiance offset correction, and the selection of optimized numerical settings. NO retrieval errors in individual observations are dominated by measurement noise and range from 5 % to 50 % in the stratosphere and thermosphere and reach 40 % to 90 % in the mesosphere. Systematic errors are typically within 10 %–30 %. Lower-thermospheric temperature errors are 5 to 50 K with a systematic component of around 20 K, the latter being dominated by non-thermodynamic equilibrium (non-LTE)-related uncertainties. NO data from different observation modes are consistent within 5 %–10 %. MIPAS version 8 temperatures have a better representation of the diurnal tide in the lower thermosphere compared to previous data versions. The new MIPAS temperatures are systematically warmer than results from the empirical US Naval Research Laboratory Mass Spectrometer Incoherent Scatter Radar (NRLMSIS) version 2.0 model by 30 to 80 K in the 100–120 km region and are colder above.

Accurate and spatially explicit information on forest fuels becomes essential to designing an integrated fire risk management strategy, as fuel characteristics are critical for fire danger estimation, fire propagation, and emissions modelling, among other aspects. This paper proposes a new European fuel classification system that can be used for different spatial scales and purposes (propagation, behaviour, and emissions). The proposed classification system is hierarchical and encompasses a total of 85 fuel types, grouped into six main fuel categories (forest, shrubland, grassland, cropland, wet and peat/semi-peat land, and urban), plus a nonfuel category. For the forest cover, fuel types include two vertical strata, overstorey and understorey, to account for both surface and canopy fuels. In addition, this paper presents the methods to map fuel types at the European scale, including the first-level of the classification system. Land cover, biogeographic datasets, and bioclimatic modelling were used. The final map, which is publicly available (https://doi.org/10.21950/YABYCN; Aragoneses et al., 2022a), included 20 fuel categories at 1 km spatial resolution. A first assessment of this map was performed using field information obtained from LUCAS (Land Use and Coverage Area frame Survey), complemented with high-resolution data. This validation exercise provided an overall accuracy of 88 % for the main fuel types and 81 % for all mapped fuel types. To facilitate the use of this fuel dataset in fire behaviour modelling, an assignment of fuel parameters to each fuel type was performed by developing a crosswalk to the standard fuel models defined by Scott and Burgan (2005; FBFMs – Fire Behavior Fuel Models), considering European climate diversity. This work has been developed within the framework of the FirEUrisk project, which aims to create a European-integrated strategy for fire danger assessment, reduction, and adaptation.

A new global O3 data product retrieved from the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) spectra with the IMK–IAA MIPAS data processor has been released. These data are based on ESA version 8 recalibrated radiance spectra with improved temporal stability. Changes in the level-2 processing with respect to previous data versions include the following: (1) the retrievals use improved temperature data and thus suffer less from the propagation of related errors. (2) The background continuum is now considered up to 58 km. (3) A priori information is now used to constrain the retrieval of the radiance offset. (4) Water vapour is fitted jointly with ozone to minimize the impact of interfering water lines. (5) A more adequate regularization has been chosen. (6) Ozone absorption lines in the MIPAS A band (685–980 cm−1) are used almost exclusively because of inconsistencies in spectroscopic data in the MIPAS AB band (1010–1180 cm−1). Only at altitudes above 50 km, where A-band ozone lines do not provide sufficient information, are ozone lines in the MIPAS AB band used. (7) Temperature-adjusted climatologies of vibrational temperatures of O3 and CO2 are considered to account for non-local thermodynamic equilibrium radiation. Ozone errors are estimated to be less than 10 % in the altitude range 20–50 km. The error budget is dominated by the spectroscopic errors, followed by the uncertainty of the instrumental line shape function, the gain calibration error, and the spectral noise. The error contribution of interfering gases is almost negligible. The vertical resolution depends on altitude and atmospheric conditions. In 2002–2004 it varies between 2.5 km at the lowest altitudes and 6 km at 70 km, while in 2005–2012 it covers 2 to 5.5 km in the same altitude range. The horizontal smearing in terms of the full width at half maximum of the horizontal component of the two-dimensional averaging kernel matrix is smaller than, or approximately equal to, the distance between two subsequent limb scans at all altitudes. This implies that the horizontal resolution is sampling-limited or optimal, respectively. An additional data version is made available that is free of the formal a priori information and thus more user-friendly for certain applications. Version 8 ozone results show a better consistency between the two MIPAS measurement periods. They seem to be more realistic than preceding data versions in terms of long-term stability, as at least a part of the drift is corrected. Further, the representation of elevated stratopause situations is improved.

Phytophthora cinnamomi is an important plant pathogen responsible for dieback diseases in plant genera including Quercus, Fagus, Castanea, Eucalyptus, and Pinus, among others, all over the world. P. cinnamomi infection exerts tremendous ecological and economic losses. Several strategies have been developed to combat this pathogenic oomycete, including the search for novel anti-oomycete compounds. In this work, a Mediterranean vascular plant, Phlomis purpurea, has been screened for secondary bioactivity against this pathogen. The genus Phlomis includes a group of herbaceous plants and shrubs described as producers of many different bioactive compounds, including several triterpenoids. Triterpenoids are well-known molecules synthesized by plants and microorganisms with potent antioxidant, antitumoral, and antimicrobial activities. We have isolated by HPLC-DAD and characterized by HPLC-MS and NMR two nortriterpenoid compounds (phlomispentaol A and phlomispurtetraolone) from the root extracts of P. purpurea. One of them (phlomispentaol A) is active against the plant pathogenic oomycete P. cinnamomi (based on in vitro inhibition bioassays). Based on their chemical structure and their relationship to other plant triterpenoids, oleanolic acid is proposed to be the common precursor for these molecules. The anti-oomycete activity shown by phlomispentaol A represents a promising alternative to counteract the worldwide-scale damage caused to forest ecosystems by this pathogen.

Research on urban biodiversity has primarily addressed the effects of urbanization and human activity synergistically as it has been virtually impossible to dissociate their impact on city wildlife. However, the anthropause resulting from COVID–19 lockdowns provided an unprecedented scenario to study the relative role of human activity on avian communities. Here we provide evidence of the relationships between human activity and bird species richness in urban areas of Colombia during its strict and subsequent relaxed lockdowns. Once the strict lockdown was lifted and human activity increased, avian species richness decreased by 32 % in 46 % of our sampling sites. Although the strict lockdown lasted only six weeks, local assemblages (mainly from low–intensity urbanization peri–urban sites) swiftly became more diverse. Our findings highlight the importance of taking human activity into account when planning cities, with important focus on greenspaces, if our aim is to conserve and enhance urban biodiversity. Such plans will require not only the cooperation of local governments but also greater awareness among the local population regarding the importance of creating livable, healthy, biodiverse, and resilient cities.

Abstract Asymmetric pumping is a sub-category of valveless pumping in which a flexible tube is rhythmically compressed in the transverse symmetry plane. Due to the resulting asymmetry between the suction and discharge pipes, a net pumping head is achieved. Asymmetric pumping is regarded as one of the main mechanisms responsible for the Liebau effect in addition to impedance pumping. However, there remains a paucity of research surrounding the governing parameters of asymmetric pumping. Here, we conducted an experimental study of the performance of an asymmetric pump, with an aim to assess its potential for extravascular flow augmentation. A custom flexible latex tube and experimental platform were developed for this purpose. We tested various tube thicknesses and pinching frequencies. Our results demonstrate that the performance is within the range of physiological requirements for pediatric circulatory devices (~ 1 L/min and

Breast cancer is the most commonly diagnosed and leading cause of cancer death among women worldwide. Mitogen-activated protein kinase-interacting kinases (MNKs) promote the expression of several oncogenic proteins and are overexpressed in several types of cancer. In human cells, there are four isoforms of MNKs. The truncated isoform MNK1b, first described in our laboratory, has a higher basal activity and is constitutively active. Aptamers are emerging in recent years as potential therapeutic agents that show significant advantages over drugs of other nature. We have previously obtained and characterized a highly specific aptamer against MNK1b, named apMNK2F, with a dissociation constant in the nanomolar range, which produces significant inhibition of proliferation, migration, and colony formation in breast cancer cells. Furthermore, its sequence analysis predicted two G-quadruplex structures. In this work, we show the optimization process of the aptamer to reduce its size, improving its stability. The obtained aptamer, named apMNKQ2, is able to inhibit proliferation, colony formation, migration, and invasion in breast cancer cells. In murine models of breast cancer, apMNKQ2 has demonstrated its efficacy in reducing tumor volume and the number of metastases. In conclusion, apMNKQ2 could be used as an anti-tumor drug in the future.

Resumen: Introducción y objetivos: Aunque se ha publicado mucho sobre el efecto de la pandemia en las urgencias traumatológicas, no se ha analizado si la incidencia de la infección o la distinta organización de los recursos disponibles según la comunidad autónoma fueron factores influyentes. Presentamos un estudio multicéntrico de tres hospitales terciarios de tres ciudades españolas con distintas características para estudiar cómo estos factores influyeron a las urgencias traumatológicas pediátricas durante la primera ola de la pandemia. Material y métodos: Presentamos un estudio retrospectivo de cohortes que compara y analiza las urgencias traumatológicas pediátricas en tres hospitales distintos durante el periodo de la primera ola de la pandemia COVID-19 y comparamos sus resultados con los del mismo periodo del año anterior, analizando el número de urgencias, la gravedad de la patología, la edad media de los pacientes, los días de ingreso y el tiempo de espera de los casos que requirieron tratamiento quirúrgico. Resultados: Se han analizado 6.474 episodios de urgencias traumatológicas infantiles. Se produjo una drástica reducción de la actividad en los tres hospitales, pero en distinta cuantía: del 83,5% en el hospital localizado en Madrid, del 75% en el hospital localizado en Valencia y del 65,9% en el ubicado en Palma de Mallorca. Las urgencias atendidas fueron de mayor gravedad en el año 2020 en comparación con el año 2019. La edad media de los pacientes atendidos durante la pandemia fue menor en comparación con el año anterior. No hubo diferencias en los días de ingreso, pero sí en la demora de la cirugía de las fracturas quirúrgicas. Conclusiones: La repercusión de la primera ola de la pandemia COVID-19 y el confinamiento decretado tuvieron una repercusión distinta en las urgencias traumatológicas pediátricas en los distintos hospitales según la incidencia de la infección y las medidas adoptadas en las diferentes comunidades autónomas. En todos los casos hubo una reducción importante de la actividad, se atendió una mayor proporción de patología media y grave, la edad media de los pacientes atendidos fue menor y se observó un retraso en las cirugías realizadas en urgencias, probablemente por la necesidad de solicitar una prueba PCR para detectar una infección por COVID-19. Abstract: Introduction and objectives: Although much has been published on the effect of the pandemic on trauma emergencies, it has not been analyzed whether the incidence of infection or different organization of available resources according to the Spanish region were influential factors. We present a multicenter study of three tertiary hospitals in three Spanish cities with different characteristics to study how these factors influenced pediatric trauma emergencies during the first wave of the pandemic. Material and methods: We present a retrospective cohort study that compares and analyzes pediatric trauma emergencies in three different hospitals during the period of the first wave of the COVID-19 pandemic and we compare them with the same period of the previous year, analyzing the number of emergencies, the severity of the pathology, the average age of the patients, the days of admission and the waiting time of the cases that required surgical treatment. Results: A total of 6,474 pediatric trauma emergency episodes have been analyzed. There was a drastic reduction in activity in the three hospitals, but in different amounts: 83.5% in the hospital located in Madrid, 75% in the hospital located in Valencia and 65.9% in the one located in Palma, Majorca. The emergencies attended were more serious in 2020 compared to 2019. The average age of patients treated during the pandemic was lower compared to the previous year. There were no differences in the days of admission, but there were differences in the delay in surgery for surgical fractures. Conclusions: The impact of the first wave of the COVID-19 pandemic and the decreed confinement had a different impact on pediatric trauma emergencies in the different hospitals according to the incidence of infection and the measures adopted in the different regions. In all cases there was a significant reduction in activity, a greater proportion of medium and severe pathologies were attended to, the average age of the patients attended was lower and a delay was observed in surgeries performed in the emergency room, probably due to the need to request a PCR test to detect a COVID-19 infection.

By using an ultradeep JWST/MIRI image at 5.6 μ m in the Hubble eXtreme Deep Field, we constrain the role of strong H α emitters (HAEs) during “cosmic reionization” at z ≃ 7–8. Our sample of HAEs is comprised of young (

A huge family of luminescent low-dimensional metal halides for optoelectronic applications has emerged recently as a green alternative to the highly toxic lead halide phosphors. To date, studies on the controlled deposition of these materials as films to be integrated into optoelectronic architectures remain scarce. Here, the synthesis and characterization of highly luminescent films of copper halide phosphors with emissions in violet: K2CuCl3, blue: Cs5Cu3Cl6I2, and green: Cs3Cu2Cl5 are reported. The films were obtained by multisource aerosol-assisted chemical vapor deposition (AACVD) from methanolic solutions at low temperature and under ambient conditions. Photoluminescent quantum yield values obtained for the films deposited on quartz substrates have values of 52% for K2CuCl3, 85% for Cs5Cu3Cl6I2, and 99% for Cs3Cu2Cl5. These values were highly influenced by the substrate since for samples deposited on glass substrates the values are 26.17% for K2CuCl3, 60.47% for Cs5Cu3Cl6I2, and 59.7% for Cs3Cu2Cl5. Different textured morphologies, with valuable applications in light-harvesting, were found for each stoichiometry. Finally, x-ray photo-emitted spectroscopy was employed to demonstrate the existence of only Cu(I) highly emissive species, suggesting that AACVD could be an excellent alternative for metal halide film deposition.

In the present work the synthesis of ZnO semiconductor thin films was performed successively using spin coating and chemical bath deposition techniques. The deposition was made by varying the concentration of zinc acetate and hexamethylenetetramine (HMTA: ZnAc) in the precursor solution. This process led to two preferred growth directions (002) and (101), both with very similar texture coefficients, too; a noticeable change in morphology of structured surface, variation in unit cell parameters and crystalline grain size. All the films turned out homogeneously submicro and microstructured and with a wurtzite-type hexagonal crystalline structure. Using pre-loaded Mathematica 11.3 software functions and an algorithm developed in it, the micrographies were analyzed to calculate the percentage of substrate-covered area which was always greater than 80%. Likewise, it also found that resistivity decreases at a higher percentage of covered area and that the variation in the shape of the photo luminescent emission spectrum can be considered as a qualitative indication of the concentration of charge carriers.

Resumen: Introducción y objetivo: La rosácea es una dermatosis acneiforme crónica donde la disrupción de la barrera cutánea puede provocar una facilidad para la sensibilización a distintos alérgenos. Nuestro objetivo es analizar la sensibilización alérgica de contacto en los pacientes con rosácea de nuestro medio. Material y métodos: Se realizó estudio de cohortes retrospectivo analizando todos los pacientes parchados en la consulta de Alergia Cutánea de nuestro servicio entre mayo de 1991 hasta mayo de 2019. Resultados: Durante el tiempo de estudio han sido remitidos a nuestra consulta un total de 200 pacientes con rosácea, el 2,1% del total de pacientes parchados en este tiempo. El 81% de los pacientes eran mujeres, con una edad media de 44,7 años. El 46,5% presentaron al menos un parche positivo, considerándose de relevancia presente (RP) en el 15%. Los parches positivos más frecuentes fueron níquel (26%), seguido de cloruro de cobalto (6,5%), isotiazolinonas (6%), PPDA (5,5%), mezcla II de perfumes (5%) y thiomersal (3,5%). Los parches positivos de RP más frecuentes fueron isotiazolinonas en 10/200 pacientes (5%), PPDA, mezcla II de fragancias, toluensulfonamida formaldehído resina en 4/200 pacientes cada uno (2%), tixocortol y mezcla I de fragancias en 2/200 cada uno (1%). El grupo de sustancias más frecuentemente detectadas fueron los metales, con una RP en el 12,6%, seguido de los fármacos con una RP en el 25,8%. Los conservantes y las fragancias fueron los siguientes grupos de sustancias más frecuentemente positivas, con una RP en el 70,8% y el 43,7%, respectivamente. La fuente de sensibilización más frecuente fueron los cosméticos, seguidos de los fármacos tópicos, destacando los corticoides y los antifúngicos tópicos. Conclusiones: Destacamos una elevada prevalencia de dermatitis alérgica de contacto en pacientes con rosácea, lo que sustenta la realización de pruebas epicutáneas, especialmente en aquellos con empeoramiento de sus lesiones en relación con la aplicación de productos cosméticos o fármacos tópicos. Abstract: Background and objective: Rosacea is a chronic acneiform skin disorder in which impaired skin barrier function can lead to sensitization to allergens. We aimed to analyze contact allergies in our patients with rosacea. Material and methods: Retrospective cohort study of all patients who underwent patch testing in our skin allergy clinic between May 1991 and May 2019. Results: A total of 200 patients with rosacea were referred to our clinic for patch testing during the study period; they represented 2.1% of all patch tested patients in the period. Eighty-one percent were women (mean age, 44.7 years). At least 1 positive patch test was recorded for 46.5%; 15% were of current relevance. The most frequent positive reaction was to nickel (26%), followed by cobalt chloride (6.5%), isothiazolinones (6%), p-phenylenediamine (5.5%), fragrance mix II (5%), and thimerosal (3.5%). The most common currently relevant patch test reactions were to isothiazolinones in 10 of the 200 patients (5%); to phenylenediamine, fragrance mix II, and toluensulfonamide formaldehyde resin in 4 patients (2%) each; and to tixocortol and fragrance mix I in 2 patients (1%) each. The allergen groups most often implicated were metals (of current relevance in 12.6%) and drugs (of current relevance in 25.8%). Preservatives and fragrances were the next most common allergen groups, and 70.8% and 43.7% of the positive reactions in these groups, respectively, were of current relevance. Cosmetics were the most frequent source of sensitization, followed by topical medications — notably corticosteroids and antifungal agents. Conclusions: We emphasize the high prevalence of allergic contact dermatitis in patients with rosacea, a finding which supports patch testing, especially if eruptions worsen when these patients use cosmetics and topical medications.

Introduction Adolescents with emotional dysregulation are at risk for self-injury. Antipsychotics are often used to manage these symptoms. Objectives The aim of the present case is to show the use of cariprazine as an effective drug for emotional dysregulation and impulsivity in a 17-year-old adolescent girl Methods Case report Results The patient was a 17-year-old female admitted to in patient psychiatric unit for a self-harm attempt due to sertraline overdose. She was being followed up for self-injury, anxiety and eating disorder symptoms. Her treatment was sertraline 200 mg, diazepam 20 mg per day and olanzapine 15 mg per day. With this medication she had gained up to 7 kgs in 4 months. A progressive change was made with cariprazine up to 3 mg and olanzapine was reduced to 2.5 mg at night. With this adjustment the patient did not present worsening in anxiety levels, with adequate impulse control and being able to perform emotional regulation strategies. Conclusions Although it has no indication in patients under 18 years of age, it shows a case of good tolerance and efficacy for the management of impulsivity by improving emotional regulation. Cariprazine is an atypical antipsychotic that works through partial agonism on dopaminergic receptors, serotonin 5-HT1A receptors and an antagonist at the 5-HT2B receptors, with moderate affinity for adrenergic, histaminergic, and cholinergic receptors reducing the likelihood of side effects Disclosure of Interest None Declared

Introduction Substance Use Disorders are frequently associated to other medical problems. The temporal evolution of the main drug requests is related to drug and drug users’ facts. COVID-19 pandemic is worthy of investigation. Objectives To analyze temporal trends in the characteristics of all medical requests to the Addiction Liaison Psychiatric Unit from January 2010 to December 2022. Methods Study data will be obtained from all patients that were referred to the Addiction Liaision Psychiatric Unit during 12 years in Hospital del Mar (Barcelona). Demographics and clinical data (substance use, medical diagnosis, dual diagnosis) will be obtained and analyzed by semesters. Results The results will be presented as soon as all data is obtained. We will explore COVID-19 pandemic implications. Conclusions . Disclosure of Interest None Declared

Introduction We often find it challenging to manage hyperactivity, low frustration tolerance and angry outbursts in patients with ASD and comorbid ADHD. Fewer drugs are approved for these disorders and these patients are more likely to develop adverse effects. Objectives The aim of this case is to show how the combination of lisdexamfetamine together with guanfacine has very positive effects on anger outbursts and boundary heteroaggressiveness in patients with ASD and ADHD. Methods Case report and literature review Results This is a 14-year-old minor admitted to the psychiatric unit after physical aggression against his family due to anger after removal of video games, requiring police intervention. He has been diagnosed since he was 11 years old with ADHD and Autism Spectrum Disorder. He was being treated with methylphenidate 54 mg and aripiprazole 10 mg. Since the beginning of the admission, the following pharmacological adjustment has been made: Methylphenidate is substituted by lisdexamfetamine up to 50 mg per day. Guanfacine has been started up to 4 mg per day and the dose of aripiprazole has been maintained. The patient had no adverse effects with adequate tolerance without sedation, hyporexia or hypotension. With this adjustment, improvement was found in the levels of restlessness and hyperactivity. The patient expressed a subjective improvement in the levels of restlessness and with a notable improvement in attention in the hospital classroom. An improvement in emotional regulation was also observed, with more tolerance to the imposition of limits, without an explosion of anger in the face of any rule during admission Conclusions The management of hyperactivity and episodes of low frustration tolerance in patients with ASD and ADHD is complex. Many studies point out the time-limited use of some antipsychotics such as risperidone or aripiprazole. This work aims to show guanfacine in combination with lisdexamfetamine as an excellent combination for the management of agitation and rage explosion in these patients. In addition, the profile of adverse effects at metabolic level is much better than that of atypical antipsychotics. Reference - Extended-Release Guanfacine for Hyperactivity in Children With Autism Spectrum Disorder. Lawrence Scahill et al. Am J Psychiatry. 2015 Dec. Disclosure of Interest None Declared

Introduction Patients with autism spectrum disorder are characterized by high anxiety when facing social situations and dealing with interpersonal relationships on a daily basis. Although initially because of their rigid personality with the norm, and their tendency to social distancing, we do not have in mind this pathology as the most likely to develop a substance use disorder. However, it is observed in the literature a remarkable percentage of patients who resort to consumption, mainly alcohol, as an anxiolytic to be able to interact in society. Objectives To show the case of a 19-year-old adult with a diagnosis of ASD who resorts to alcohol consumption in her daily life as a strategy to manage anxiety in social situations. Methods Case report and literatura review Results This is a 19-year-old woman with a recent diagnosis of ASD. She is studying biotechnology and lives with her parents and 3 siblings. The patient reports difficulty in social relationships since early childhood, with experiences of school bullying. She expresses desire to relate with others, although she does it in an inadequate way, with difficulty in detecting nonverbal language, irony and anger when she does not understand a joke. The patient confesses that since she was 16 years old she has consumed alcohol to mitigate the anxiety caused by facing a group of people. She says that she feels that it relaxes her and facilitates interaction, making it more fluid and less tense. However, she recognizes that initially she used to drink 1 or 2 beers, but now she needs to drink up to 2 glasses of gin, recognizing this as something problematic. Conclusions The literature shows how patients with ASD can also present substance use disorder. It has been shown that about 10% of these patients have an abusive use of alcohol. Other samples show wider ranges (7-71%) of prevalence of alcohol consumption in patients with autism. In relation to cannabis, it is seen that around 3% of these patients consume it. These patients seek its anxiolytic effect and to reduce mental health symptoms. In addition, the purchase of alcohol does not involve high social interaction to obtain it, since it is a substance that can be purchased legally. It is important to explore alcohol consumption in consultation with patients with ASD to help them develop more functional anxiety management strategies. Reference Prevalence of psychiatric disorders in adults with autism spectrum disorder: A systematic review and meta-analysis. Lugo-Marín.J et al. 2019. Research in Autism Spectrum Disorders Volume 59, March 2019, Pages 22-33 Disclosure of Interest None Declared

Introduction Addiction Liaison Pychiatric Units are frequently requested by other medical services due to the high prevalence of medical pathologies in substance use disorders. We intend to know patient’s characteristics in order to improve the approach. ObjectivesTo describe patient characteristics of all medical request to the Addiction Liaison Pyshicatric Unit from January 2010 to December 2022. Methods Study data will be obtained from all patients that were referred to the Addiction Liaison Psychiatric Unit to assess addictive disorders and withdrawal symptoms related to drugs during 12 years in Hospital del Mar (Barcelona, Spain). Demographics and clinical data (substance use, medical comorbidity and dual diagnosis) were obtained. ResultsThe results will be presented as soon as all data is obtained. We will explore COVID-19 pandemic implications. Conclusions: Disclosure of Interest None Declared

Introduction Central nervous system (CNS) tumours are the most common type of solid tumour in the paediatric population. Although advances in treatment have improved survival rates, there is a substantial body of literature documenting the potential long-term effects such as psychological, neurocognitive and health-related sequelae experienced by survivors of paediatric brain tumours. TMS is a non-invasive brain stimulation technique that uses electrical stimuli applied to the cranial surface to restore neuronal connections damaged because of CNS disruption (Burke et. al., 2019). Objectives To test the efficacy of TMS in a patient diagnosed with a CNS tumour who reported pain and suffered severe cognitive-behavioural alterations refractory to other pharmacological treatments. Methods Case Presentation. A 12-year-old boy diagnosed with a hypothalamic-pituitary tumour at the age of 9, having received surgical treatment, radiotherapy and chemotherapy. He suffered loss of vision, cognitive-behavioural and emotional sequelae, and pain, for which he received various pharmacological treatments without benefit. Treatment. The patient underwent a total of 25 sessions where each session took 20 minutes to complete for 3 sessions per week. TMS intervention consisted of 1200 inhibitory magnetic pulses with a frequency of 1hz on right DLPFC at an intensity of 110% of resting motor threshold. Stimulations were carried out using a Magventure MagPro X100 equipment with a double-cone coil. The clinical assessment included The Silhouettes Fatigue Scale (PHQ-9), Pain Catastrophizing Scale (PCS) and Numerical Rating Scale (NRS), verbal subtests of the Weschler Intelligence Scale for Children (WISC-V), Patient Health Questionnaire (PHQ-9) and the Sleep Disturbance Scale for Children, SDSC Results In the post-treatment clinical interview with the family, qualitative changes included a decrease in subjective complaints of pain and fatigue. The family reported that the child stopped sleeping tied up after the intervention and a significant change in slowness was observed, which was accompanied by a higher level of awareness and consequently a slight improvement at the behavioural level, which at the present time does allow for psychological intervention. The psychometric results were clinically improved for psychomotor activity, sleep, emotional alterations, and all cognitive domains. Conclusions 25 sessions of TMS in the right DLPFC could show beneficial effects on pain, fatigue, cognition, health and sleep variables in patients with drug-resistant sequelae derived from CNS tumours. Longitudinal studies with larger sample sizes are needed to determine whether the effects observed after TMS intervention in paediatric patients with CNS diseases are significant. Disclosure of Interest None Declared

Introduction We present the case of a 41-year-old male patient with multiple psychiatric diagnoses, he was diagnosed with agenesis of the corpus callosum, which explains his clinical presentation. Objectives The objective is to carry out a brief review of the symptoms associated with the agenesis of the corpus callosum. Methods The patient has been diagnosed with ADHD, cyclothymia, depressive anxiety disorder and social phobia. He has been treated with a multitude of drugs such as antidepressants, anxiolytics, stimulants and even low-dose antipsychotics. Despite the pharmacological treatments received, as well as the therapies, the patient’s functionality has progressively worsened, to the point of restricting going out of the home or maintaining a stable job. Biographical data were collected, including psychomotor retardation and inappropriate laughter. He showed mannerisms such as fluttering and low frustration tolerance. He was slow to respond to his name and showed little affective resonance with his sister and parents. Restrictive interests, especially with English culture, for which he later studied English philology. On the other hand, his mother explains that he had no symbolic play and that, from early childhood, he had difficulties in relationships with peers. Due to the aforementioned clinical manifestations, the functional worsening and the examination carried out in the consultation room, it was decided to extend the study with a brain MRI, where an agenesis of the corpus callosum was observed. Results Agenesis of the corpus callosum is a malformation of the central nervous system, which affects one in every 4000 births. It can be partial or complete, and occurs between the 7th-20th week of gestation. Agenesis of the corpus callosum presents with a triad of symptoms: - Reduced interhemispheric communication of sensory-motor information. - Increased information processing time - Difficulty in abstract thinking. This triad causes difficulties not only cognitively, but also socially. There is difficulty in integrating and learning new verbal and visual information. Tendency to literalism, with difficulty in understanding double meanings. They also have difficulty understanding non-verbal language and reading emotions, which makes interaction with peers difficult. All these symptoms can sometimes be confused with symptoms compatible with Autism Spectrum Disorder. Conclusions After the diagnosis and after focusing the patient’s treatment on the most limiting symptoms of his daily life, an integrated approach was initiated, not only at a pharmacological level, with the use of antidepressants and anxiolytics, but also from a psychotherapeutic point of view, working on those areas in which the patient is most dysfunctional. He was accompanied in the disability application process, as well as helped in the search for associations for adults with ASD, finding there the answer to his symptoms and difficulties. Disclosure of Interest None Declared

Obesity is one of the main risk factors for type 2 diabetes, and peroxisome proliferator-activated receptor γ (PPARγ) is considered a promising pathway on insulin sensitivity and adipose tissue metabolism. The search for molecules acting as insulin sensitizers have increased, especially for molecules that block PPARγ-Ser273 phosphorylation, without reaching full agonism. We evaluated the in vivo effects of AM-879, a PPARγ non-agonist, and found that AM-879 exerts different effects in mice depending on the dose. At lower doses, this ligand decreased BAT, increased leptin and Crh expression. However, at a higher dose, it promoted improvement on insulin sensitivity, ameliorates expression of metabolism-related genes, decreased the expression of genes related to liver toxicity, maintaining body weight and adipocyte size. These results present a new lead molecule to ameliorates insulin resistance and confirm AM-879 as a PPARγ non-agonist which blocks Ser273 phosphorylation as a good strategy to modulate insulin sensitivity without developing the adverse effects promoted by PPARγ full agonists.

¿Audaz o tímido? Examinando el comportamiento de toma de riesgo y neofobia de los gorriones comunes invasivos y no invasivos Dado que el comportamiento proporciona un marco útil para comprender la especialización, la personalidad animal puede ayudar a explicar la capacidad invasiva de las aves. La invasión implica la dispersión por áreas desconocidas y podría requerir cambios en el comportamiento o agrupaciones espaciales basadas en la personalidad. La reducción de la neofobia y el aumento del comportamiento de exploración podrían permitir a los individuos colonizar nuevas áreas a medida que prueban y utilizan recursos que no les son familiares. En este trabajo suponemos que los individuos de gorrión común (Passer domesticus) mostrarán un comportamiento más audaz en las poblaciones invasivas que en las poblaciones no invasivas. En este estudio evaluamos la toma de riesgo y la neofobia en machos de gorrión común de Barcelona (donde se considera nativo) y de Ciudad de México (donde es invasivo) capturados en dos hábitats diferentes (urbano y no urbano). Evaluamos la latencia para entrar en la jaula experimental y para explorarla, así como la latencia para alimentarse y el tiempo de alimentación en presencia de un objeto extraño. Encontramos que los gorriones de Ciudad de México, tanto de hábitats urbanos como no urbanos, entraron más rápido en la jaula experimental que los gorriones de Barcelona. El resultado fue similar para el tiempo que les tomó comenzar a explorar la jaula. No encontramos diferencias entre ciudades y hábitats en cuanto a la latencia para alimentarse y el tiempo que les tomó alimentarse en presencia de un objeto extraño. Nuestros resultados apoyan parcialmente la idea de que las poblaciones invasivas de Ciudad de México son más atrevidas que las de Barcelona. El comportamiento es un componente importante de la plasticidad y su variabilidad puede tener un efecto importante en la adaptación a situaciones locales. Se deberían llevar a cabo otros estudios para desentrañar los mecanismos que explican las diferencias de personalidad que se encuentran entre poblaciones de distintos orígenes, así como comparando poblaciones con diferente densidad demográfica y teniendo en cuenta diferentes contextos de disponibilidad de alimentos.

Resumen: Introducción: La infección congénita por citomegalovirus (CMV) supone una importante causa de discapacidad. Existen escasas evidencias acerca del valor pronóstico de las lesiones presentes en los estudios de neuroimagen. Objetivo: Analizar la gravedad de las lesiones en la resonancia magnética (RM) y la ecografía transfontanelar, y su relación con déficits neurológicos a largo plazo. Pacientes y métodos: Se realizó un estudio observacional analítico retrospectivo de 36 pacientes con infección congénita por CMV. Se revisaron los estudios de neuroimagen y se clasificaron según la escala de Noyola et al. modificada. Se relacionaron los hallazgos de neuroimagen con la afectación neurológica en su última visita en la consulta de neuropediatría. Resultados: Un total de 36 pacientes fueron estudiados, habiéndose realizado ecografía transfontanelar en 30 y RM cerebral en 29. La ecografía transfontanelar estuvo alterada en 20/30 pacientes, de los cuales, 11 tuvieron alteración en la RM (p = 0,04) y 10 afectación neurológica (p = 0,008). Tuvo una sensibilidad del 83,3%, IC 90%: 58-100 y una especificidad del 44,4%, IC 90%: 18,7-70,2 para la predicción de secuelas neurológicas. La RM estuvo alterada en 20/29 pacientes. Dieciséis de ellos tuvieron afectación neurológica (p 2 were correlated with psychomotor retardation (P

The early introduction of a low phenylalanine (Phe) diet has been demonstrated to be the most successful treatment in subjects with phenylketonuria (PKU), especially for preventing severe cognitive and neurological damages. However, it still concerns that even if treated in the first months of life with supplements and following a diet, they can show slight scores below people without PKU in neuropsychological assignments. We investigated 20 adults with classical PKU aged 19–48 years (mean age 29 years) and 20 heathy controls matched by age, gender, and years of education. Patients and controls were assessed with an extended neuropsychological battery, as well as psychological aspects and quality of life, also the last Phe level result was obtained. Results showed that the most affected cognitive domains are processing speed, executive functioning, memory, and also theory of mind, but very well-preserved verbal fluency, language, and visuospatial functioning. In quality of life, some significant results were seen specially in anxiety of Phe levels, anxiety of Phe levels during pregnancy, guilt if poor adherence to supplements, and if dietary protein restriction not followed. No significant results were obtained for the psychological variables. In conclusion, it has been shown that a combination of a low Phe diet, supplement intake, and keeping Phe levels in a low range seems appropriate to have the most normal and alike cognitive performance to persons without PKU.

Introduction and objectives: Although much has been published on the effect of the pandemic on trauma emergencies, it has not been analysed whether the incidence of infection or different organisation of available resources according to the Spanish region were influential factors. We present a multicenter study of three tertiary hospitals in three Spanish cities with different characteristics to study how these factors influenced paediatric trauma emergencies during the first wave of the pandemic. Material and methods: We present a retrospective cohort study that compares and analyzes paediatric trauma emergencies in three different hospitals during the period of the first wave of the COVID-19 pandemic and we compare them with the same period of the previous year, analyzing the number of emergencies, the severity of the pathology, the average age of the patients, the days of admission and the waiting time of the cases that required surgical treatment. Results: A total of 6474 paediatric trauma emergency episodes have been analysed. There was a drastic reduction in activity in the three hospitals, but in different amounts: 83.5% in the hospital located in Madrid, 75% in the hospital located in Valencia and 65.9% in the one located in Palma, Majorca. The emergencies attended were more serious in 2020 compared to 2019. The average age of patients treated during the pandemic was lower compared to the previous year. There were no differences in the days of admission, but there were differences in the delay in surgery for surgical fractures. Conclusions: The impact of the first wave of the COVID-19 pandemic and the decreed confinement had a different impact on paediatric trauma emergencies in the different hospitals according to the incidence of infection and the measures adopted in the different regions. In all cases there was a significant reduction in activity, a greater proportion of medium and severe pathologies were attended to, the average age of the patients attended was lower and a delay was observed in surgeries performed in the emergency room, probably due to the need to request a PCR test to detect a COVID-19 infection. Resumen: Introducción y objetivos: Aunque se ha publicado mucho sobre el efecto de la pandemia en las urgencias traumatológicas, no se ha analizado si la incidencia de la infección o la distinta organización de los recursos disponibles según la comunidad autónoma fueron factores influyentes. Presentamos un estudio multicéntrico de 3 hospitales terciarios de 3 ciudades españolas con distintas características para estudiar cómo estos factores influyeron a las urgencias traumatológicas pediátricas durante la primera ola de la pandemia. Material y métodos: Presentamos un estudio retrospectivo de cohortes que compara y analiza las urgencias traumatológicas pediátricas en 3 hospitales distintos durante el periodo de la primera ola de la pandemia COVID-19 y comparamos sus resultados con los del mismo periodo del año anterior, analizando el número de urgencias, la gravedad de la dolencia, la edad media de los pacientes, los días de ingreso y el tiempo de espera de los casos que requirieron tratamiento quirúrgico. Resultados: Se han analizado 6.474 episodios de urgencias traumatológicas infantiles. Se produjo una drástica reducción de la actividad en los 3 hospitales, pero en distinta cuantía: del 83,5% en el hospital localizado en Madrid, del 75% en el hospital localizado en Valencia y del 65,9% en el ubicado en Palma de Mallorca. Las urgencias atendidas fueron de mayor gravedad en el año 2020 en comparación con el año 2019. La edad media de los pacientes atendidos durante la pandemia fue menor en comparación con el año anterior. No hubo diferencias en los días de ingreso, pero sí en la demora de la cirugía de las fracturas quirúrgicas. Conclusiones: La repercusión de la primera ola de la pandemia de COVID-19 y el confinamiento decretado tuvieron una repercusión distinta en las urgencias traumatológicas pediátricas en los distintos hospitales según la incidencia de la infección y las medidas adoptadas en las diferentes comunidades autónomas. En todos los casos hubo una reducción importante de la actividad, se atendió una mayor proporción de dolencias medias y graves, la edad media de los pacientes atendidos fue menor y se observó un retraso en las cirugías realizadas en urgencias, probablemente por la necesidad de solicitar una prueba PCR para detectar una infección por COVID-19.

Abstract Background There is an urgent need for highly efficacious antiviral therapies in immunosuppressed hosts who develop coronavirus disease (COVID-19), with special concern for those affected by hematological malignancies. Case presentation Here, we report the case of a 75-year-old male with chronic lymphocytic leukemia who was deficient in CD19+CD20+ B-lymphocyte populations due to previous treatment with anti-CD20 monoclonal antibodies. The patient presented with severe COVID-19 pneumonia due to prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and was treated with two courses of the antiviral plitidepsin on a compassionate use basis. The patient subsequently achieved an undetectable viral load, and his pneumonia resolved. Conclusions Treatment with plitidepsin was well-tolerated without any further hematological or cardiovascular toxicities. This case further supports plitidepsin as a potential antiviral drug in SARS-CoV-2 patients affected by immune deficiencies and hematological malignancies.