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Abstract Background Missing data in confounding variables present a frequent challenge in generating evidence using real-world data, including electronic health records (EHR). Our objective was to apply a recently published toolkit for characterizing missing data patterns and based on the toolkit results about likely missingness mechanisms, illustrate the decision-making process for analyses in an empirical case example. Methods We utilized the Structural Missing Data Investigations (SMDI) toolkit to characterize missing data patterns in the context of a pharmacoepidemiology study comparing cardiovascular outcomes of initiating sodium-glucose-cotransporter-2 inhibitors (SGLT2i) and dipeptidyl peptidase‐4 inhibitors (DPP‐4i) among older adults. The study used a linked EHR-Medicare claims dataset from Duke Health patients (2015–2017), focusing on partially observed confounders from EHR data (HbA1c lab and body mass index [BMI] values). Our analysis incorporated SMDI's descriptive functions and diagnostic tests to explore missingness patterns and determine missingness mitigation approaches. We used findings from these investigations to inform estimation of adjusted hazard ratios comparing the two classes of medications. Results High levels of missingness were noted for important confounding variables including HbA1c (63.6%) and BMI (16.5%). Diagnostic tests resulted in output that described: 1) the distributions of patient characteristics, exposure, and outcome between patients with or without an observed value of the partially observed covariate, 2) the ability to predict missingness based on observed covariates, and 3) estimate if the missingness of a partially observed covariate is differential with respect to the outcome. There was evidence that missingness could be sufficiently described using observed data, which allowed multiple imputation by chained equations using random forests to address missing confounder data in estimating treatment effects. Multiple imputation resulted in improved alignment of effect estimates with previous studies. Conclusions We were able to demonstrate the practical application of the SMDI toolkit in a real-world setting. Application of the SMDI toolkit and the resulting insights of potential missingness patterns can inform the choice of appropriate analytic methods and increase transparency of research methods in handling missing data. This type of approach can inform analytic decision making and may increase our ability to generate evidence from real-world data.

Abstract This study provides an analysis of atmospheric neutrino oscillations at the ESSnuSB far detector facility. The prospects of the two cylindrical Water Cherenkov detectors with a total fiducial mass of 540 kt are investigated over 10 years of data taking in the standard three-flavor oscillation scenario. We present the confidence intervals for the determination of mass ordering, θ 23 octant as well as for the precisions on sin2 θ 23 and Δ m 31 2 $$ \left|\Delta {m}_{31}^2\right| $$ . It is shown that mass ordering can be resolved by 3σ CL (5σ CL) after 4 years (10 years) regardless of the true neutrino mass ordering. Correspondingly, the wrong θ 23 octant could be excluded by 3σ CL after 4 years (8 years) in the case where the true neutrino mass ordering is normal ordering (inverted ordering). The results presented in this work are complementary to the accelerator neutrino program in the ESSnuSB project.

There is evidence that maternal viral load of HCV during delivery influences the risk for Mother-to-child transmission (MTCT), but this does not explain all cases. We study the role of the immunogenetic profile (HLA, KIRs and KIR-ligand binding) of mothers and children in HCV-MTCT and in chronicity in the children.79 HCV-RNA (+) mothers and their 98 children were included. 24 children were infected, becoming chronic in 8 cases and clearing in 16. HLA-class-I and II and KIRs were determined by Luminex.MTCT study: The presence of HLA-C1-ligand in mothers and/or their children reduces the risk of transmission (mothers: Pc = 0.011, children: P = 0.033), whereas the presence of HLA-C2C2-ligand in mothers increases it (Pc = 0.011). In children KIR2DL3-HLA-C1 is a protector factor (Pc = 0.011). Chronicity in children study: Maternal DQA1*01 allele (Pc = 0.027), KIR2DS1 (Pc = 0.011) or KIR3DS1 (Pc = 0.011) favours chronicity in the child. The presence of the DQB1*03 allele (Pc = 0.027) and KIR2DS3 (P = 0.056) in the child and homozygosity for KIR3DL1/3DL1 (Pc = 0.011) and for the HLA-Bw4/Bw4 ligand (P = 0.027) is associated with viral clearance, whereas the presence of HLA-Bw6 ligand (P = 0.027), the binding of KIR3DS1-HLA-Bw4 (P = 0.037) and heterozygosity for KIR3DL1/3DS1 (Pc = 0.011) favour viral chronicity. Mother/child allele matching: In the joint HLA analysis, matching was greater between mothers and children with chronic infection vs those who had cleared the virus (67%±4.1 vs 57%±1.2, P = 0.003).The HLA-C1 ligand in the mother is related to MTCT, while several genetic factors of the mother or child are involved in the chronification or clearance of infection in the child. Matching allelic data is considered to be an indicator of HCV chronicity in the child and can be used as a potential prognostic test. This implies that NK cells may play a previously undocumented role in protecting against MTCT and that both NK cell immunity and adaptive T-cell responses may influence viral clearance in infected children.

El Parque Provincial Ischigualasto (PPI) fue declarado Patrimonio Natural de la Humanidad por la UNESCO en el año 2000, junto con el Parque Nacional Talampaya. Se han realizado relevamientos de la diversidad de mamíferos, aves, anfibios y reptiles presentes en el PPI y una actualización de la herpetofauna. En este trabajo reportamos el primer registro de Oxyrhopus rhombifer bachmanni para el PPI. Con este registro, se incrementa a seis el número de especies de serpientes registradas en el PPI, dando una riqueza total de 26 especies para la herpetofauna presente en el mismo. Además, el conocimiento de la distribución de la herpetofauna dentro del PPI podría ser utilizada como herramienta para la toma de decisiones de manejo en esta área natural protegida.

Frontal ablation is responsible for a large fraction of the mass loss from tidewater glaciers. The main contributors to frontal ablation are iceberg calving and submarine melting, with calving often being the largest. However, submarine melting, in addition to its direct contribution to mass loss, also promotes calving through the changes induced in the stress field at the glacier terminus, so both processes should be jointly analysed. Among the factors influencing submarine melting, the formation of a buoyant plume due to the emergence of fresh subglacial water at the glacier grounding line plays a key role. In this study we used Elmer/Ice to develop a 3D glacier dynamics model including calving and subglacial hydrology coupled with a line plume model to calculate the calving front position at every time step. We applied this model to the Hansbreen–Hansbukta glacier–fjord system in southern Spitsbergen, Svalbard, where a large set of data are available for both the glacier and the fjord from September 2008 to March 2011. We found that our 3D model reproduced the expected seasonal cycle of advance–retreat. Besides, the modelled front positions were in good agreement with the observed front positions at the central part of the calving front, with longitudinal differences, on average, below 15 m for the period from December 2009 to March 2011. But there were regions of the front, especially the eastern margin, that presented major differences.

Background: Ischaemic stroke may be a major complication of SARS-CoV-2 infection. Studying and characterising the different aetiological subtypes, clinical characteristics, and functional outcomes may be valuable in guiding patient selection for optimal management and treatment. Methods: Data were collected retrospectively on consecutive patients with COVID-19 who developed acute focal brain ischaemia (between 1 March and 19 April 2020) at a tertiary university hospital in Madrid (Spain). Results: During the study period, 1594 patients were diagnosed with COVID-19. We found 22 patients with ischaemic stroke (1.38%), 6 of whom did not meet the inclusion criteria. The remaining 16 patients were included in the study (15 cases of ischaemic stroke and one case of transient ischaemic attack).Median baseline National Institutes of Health Stroke Scale score was 9 (interquartile range: 16), and mean (standard deviation) age was 73 years (12.8). Twelve patients (75%) were men. Mean time from COVID-19 symptom onset to stroke onset was 13 days. Large vessel occlusion was identified in 12 patients (75%).We detected elevated levels of D-dimer in 87.5% of patients and C-reactive protein in 81.2%. The main aetiology was atherothrombotic stroke (9 patients, 56.3%), with the predominant subtype being endoluminal thrombus (5 patients, 31.2%), involving the internal carotid artery in 4 cases and the aortic arch in one. The mortality rate in our series was 44% (7 of 16 patients). Conclusions: In patients with COVID-19, the most frequent stroke aetiology was atherothrombosis, with a high proportion of endoluminal thrombus (31.2% of patients). Our clinical and laboratory data support COVID-19–associated coagulopathy as a relevant pathophysiological mechanism for ischaemic stroke in these patients. Resumen: Introducción: El ictus isquémico puede ser una complicación grave en los pacientes con infección por SARS-CoV-2.Estudiar y caracterizar los diferentes subtipos etiológicos, las características clínicas y el pronóstico funcional podrá resultar útil en la selección de pacientes para un manejo y tratamiento óptimos. Métodos: La recogida de variables se hizo de forma retrospectiva en pacientes consecutivos con infección por COVID-19 que desarrollaron un episodio de isquemia cerebral focal (entre el 1 de Marzo 1, 2020, y el 19 de Abril, 2020). Se llevó a cabo en un hospital universitario de tercer nivel en la Comunidad de Madrid. (España). Resultados: Durante el período de estudio 1594 pacientes fueron diagnosticados de infección por COVID 19. Identificamos 22 pacientes con ictus isquémico (1.38%), de estos no cumplieron los criterios de inclusión 6. Un total de 16 pacientes con isquemia cerebral focal constituyeron la serie del estudio (15 con ictus isquémico y 1 con accidente isquémico transitorio).En la valoración basal en el National Institutes of Health Stroke Scale (NIHSS) la mediana fue de 9 (Rango Intercuartil RIQ: 16), la edad media fue de 73 años (DE ± 12.8). 12 pacientes fueros varones (75%). El tiempo desde los síntomas de COVID-19 hasta el ictus fue de 13 días. Se encontró oclusión de gran vaso en 12 pacientes (75%).El dímero –D estuvo elevado en el 87.5% y la proteína C reactiva en el 81.2% de los casos. La etiología más frecuente del ictus isquémico fue la aterotrombosis (9 pacientes, 56.3%) con un subtipo predominante que fue el trombo endoluminal sobre placa de ateroma (5 pacientes, 31.2%), 4 de ellos en la arteria carótida interna y uno de ellos en el arco aórtico. La mortalidad en nuestra serie fue del 44% (7 de 16 pacientes). Conclusiones: En los pacientes con ictus y COVID-19 la etiología más frecuente fue la aterotrombótica con una elevada frecuencia de trombo endoluminal sobre placa de ateroma (31.2% de los pacientes). Nuestros hallazgos clínicos y de laboratorio apoyan la coagulopatía asociada a COVID-19 como un mecanismo etiopatogénico relevante en el ictus isquémico en este contexto.

The European Aerosol Research Lidar Network (EARLINET), part of the Aerosols, Clouds and Trace gases Research Infrastructure (ACTRIS), organized an intensive observational campaign in May 2020, with the objective of monitoring the atmospheric state over Europe during the COVID-19 lockdown and relaxation period. Besides the standard operational processing of the lidar data in EARLINET, for seven EARLINET sites having collocated sun-photometric observations in the Aerosol Robotic Network (AERONET), a network exercise was held in order to derive profiles of the concentration and effective column size distributions of the aerosols in the atmosphere, by applying the GRASP/GARRLiC (from Generalized Aerosol Retrieval from Radiometer and Lidar Combined data – GARRLiC – part of the Generalized Retrieval of Atmosphere and Surface Properties – GRASP) inversion algorithm. The objective of this network exercise was to explore the possibility of identifying the anthropogenic component and of monitoring its spatial and temporal characteristics in the COVID-19 lockdown and relaxation period. While the number of cases is far from being statistically significant so as to provide a conclusive description of the atmospheric aerosols over Europe during this period, this network exercise was fundamental to deriving a common methodology for applying GRASP/GARRLiC to a network of instruments with different characteristics. The limits of the approach are discussed, in particular the missing information close to the ground in the lidar measurements due to the instrument geometry and the sensitivity of the GRASP/GARRLiC retrieval to the settings used, especially for cases with low aerosol optical depth (AOD) like the ones we show here. We found that this sensitivity is well-characterized in the GRASP/GARRLiC products, since it is included in their retrieval uncertainties.

Background and Objectives: The Coronal Plane Alignment of the Knee (CPAK) classification is a pragmatic distribution of nine phenotypes for coronal knee alignment that can be used on healthy and arthritic knees. Our study aimed to describe the CPAK distributions in a Spanish southeast osteoarthritic population and compare them to other populations’ published alignment distributions. Method and Materials: Full-leg standing X-rays of the lower limb from 528 cases originating from the so-called Vega Alta del Segura (southeast of the Iberian Peninsula) were retrospectively analysed. We measured the mechanical hip–knee–ankle, lateral distal femoral, and medial proximal tibial angles. We calculated the arithmetic hip–knee–ankle angle and the joint line obliquity to classify each case according to the criteria of the CPAK classification. Results: Based on the aHKA result, 59.1% of the cases were varus (less than −2°), 32.7% were neutral (0° ± 2°), and 8.2% were valgus (greater than +2°). Based on the JLO result, 56.7% of the cases had a distal apex (less than 177°), 39.9% had a neutral apex (180° ± 3°), and 3.4% had a proximal apex (greater than 183°). The most common CPAK distribution in our Spanish southeast osteoarthritic population was type I (30.7%), followed by type IV (25.9%), type II (21%), type V (11.2%), type III (5%), type VI (2.8%), type VII (2.4%), type VIII (0.6%), and type IX (0.4%). Conclusions: We described the distribution according to the CPAK classification in a sample of the osteoarthritic population from southeastern Spain. In our sample, more than 75% of the patients were classified as type I, II, and IV.

Abstract The genus Ceratocystis includes many phytopathogenic fungi that affect different plant species. One of these is Ceratocystis cacaofunesta, which is pathogenic to the cocoa tree and causes Ceratocystis wilt, a lethal disease for the crop. However, little is known about how this pathogen interacts with its host. The knowledge and identification of possible genes encoding effector proteins are essential to understanding this pathosystem. The present work aimed to predict genes that code effector proteins of C. cacaofunesta from a comparative analysis of the genomes of five Ceratocystis species available in databases. We performed a new genome annotation through an in-silico analysis. We analyzed the secretome and effectorome of C. cacaofunesta using the characteristics of the peptides, such as the presence of signal peptide for secretion, absence of transmembrane domain, and richness of cysteine residues. We identified 160 candidate effector proteins in the C. cacaofunesta proteome that could be classified as cytoplasmic (102) or apoplastic (58). Of the total number of candidate effector proteins, 146 were expressed, presenting an average of 206.56 transcripts per million. Our database was created using a robust bioinformatics strategy, followed by manual curation, generating information on pathogenicity-related genes involved in plant interactions, including CAZymes, hydrolases, lyases, and oxidoreductases. Comparing proteins already characterized as effectors in Sordariomycetes species revealed five groups of protein sequences homologous to C. cacaofunesta. These data provide a valuable resource for studying the infection mechanisms of these pathogens in their hosts.

INTRODUCCIÓN. La enseñanza de la gramática es tradicionalmente el núcleo didáctico en la materia de lengua castellana en la enseñanza preuniversitaria, pero su planteamiento metodológico ha sido cuestionado por el dudoso impacto que el conocimiento de la estructura de la lengua puede tener en el desarrollo de la competencia comunicativa de los estudiantes. Con la LOMLOE y la orientación de la educación hacia el desarrollo de competencias, deberían aplicarse cambios procedimentales que redundasen en la eficacia comunicativa. MÉTODO. Para corroborar la necesidad de esos cambios discutidos desde hace décadas de manera recurrente, se ha llevado a cabo un estudio metacognitivo con 355 estudiantes del grado en Maestro de Educación Primaria mediante el cuestionario ExCOGE, validado a través del método Delphi. Se ha realizado un análisis cualitativo para conocer las creencias epistémicas de los estudiantes sobre su experiencia de aprendizaje de la gramática, su motivación y sus futuras intenciones docentes. RESULTADOS. Los resultados reflejan una actitud acorde con la crítica más extendida, que considera el trabajo del docente poco actualizado; los contenidos gramaticales, recurrentes y sin perspectiva práctica; y la metodología, mecánica, sin reflexión y desmotivadora. DISCUSIÓN. La mejor intención de los futuros maestros es enseñar gramática reorientando los contenidos hacia el aprendizaje competencial. De este modo, sí parece que los cambios exigidos en la enseñanza de la gramática desde hace décadas se perciben como una necesidad presente y una realidad de intenciones futuras.

This work uses sandbox analog models to analyze the formation and subsequent inversion of a decoupled extensional system comprised of two segmented half-grabens separated by a diffuse accommodation zone with thick early syn-rift salt. The segmented half-grabens strike perpendicular to the direction of extension and subsequent shortening. Rifting first created a basement topography that was infilled by model salt, followed by a second phase of extension and sedimentation, followed afterwards by inversion. During the second phase of extension, syn-rift syncline minibasins developed above the basement extensional system and extended beyond the confines of the fault blocks. Sedimentary downbuilding and extension initiated the migration of model salt to the basement highs, forming salt anticlines, reactive diapirs, and salt walls perpendicular to the direction of extension, except for along the intervening accommodation zone where a slightly oblique salt anticline developed. Inversion resulted in decoupled cover and basement thrust systems. Thrusts in the cover system nucleated along squeezed salt structures and along primary welds. New primary welds developed where the cover sequence touched down on basement thrust tips due to uplift, salt extrusion, and syn-contractional downbuilding caused by the loading of syn-contractional sedimentation. Model geometries reveal the control imposed by the basement configuration and distribution of salt in the development of a thrust front from the inversion of a salt-bearing extensional system. In 3D, the interaction of salt migrating from adjacent syn-rift basins can modify the expected salt structure geometry, which may in turn influence the location and style of thrust in the cover sequence upon inversion. Results are compared to the Northern Lusitanian Basin, offshore Portugal, and the Isábena area of the South-Central Pyrenees, Spain.

In 2018, the European Space Agency launched the first Doppler wind lidar system into space, providing wind observation profiles from the lower stratosphere down to the surface in two different channels based on the scene classification: cloudy or clear. A statistical validation campaign of Aeolus wind products has been performed with a ground-based Doppler lidar system and radiosondes at the Aerosol, Clouds and Trace Gases Research Infrastructure (ACTRIS)–Andalusian Global ObseRvatory of the Atmosphere (AGORA) facility in Granada (Spain). The validation activities with the automatic ground-based lidar system lasted from July 2019 to the orbit shift of June 2021. Aeolus data from two different processing baselines (10 and 11) were validated with 30 min averages of coincident ground-based lidar measurements, using a 100 km horizontal spatial collocation criterion. This resulted in 109 collocations and a mean observation distance from the ground-based lidar system of ∼50 km. The comparison did not raise any significant over- or underestimation of Aeolus horizontal line-of-sight wind speed during that period for the Rayleigh-clear and Mie-cloudy configurations. However, the ground-based lidar measurements were limited to the lower 3.5 km of the atmosphere and, consequently, the obtained results. Multiple analyses were performed varying the criteria of maximum distance and the average period for the ground-based lidar measurements in order to confirm the reliability of the criteria considered. A separate study was performed with Aeolus products after the orbit shift (baseline 12) with different collocation criteria (mean observation distance of ∼75 km, to the station), from July 2021 to May 2022. A set of seven radiosondes were launched with the aim of increasing their coincidence in space and time with the satellite overpass (∼30 min before). The radiosondes could provide full vertical coverage of Aeolus profiles (from the surface up to ∼20 km above sea level), and the comparison did not yield any significant over- or underestimation of the Rayleigh-clear wind speed, while the Mie-cloudy wind speed was significantly overestimated. Multiple analyses were performed in order to test how the spatiotemporal collocation of the radiosonde affected the results. Radiosondes not ideally collocated were proven to still be useful for comparison with the Rayleigh-clear observations but not with the Mie-cloudy observations.

Background The management of acromioclavicular (AC) joint dislocation remains controversial. Recently, anatomic coracoclavicular (CC) fixation with a double clavicular tunnel and three flip-buttons has shown promising results. This study aimed to evaluate functional and radiological outcomes in patients with high-grade AC joint dislocation treated with anatomic CC fixation using double clavicular tunnels and three flip-buttons. Methods A retrospective, unicentric study was performed. The study included patients with high-grade AC joint dislocation who underwent surgery with anatomic CC fixation using double clavicular tunnels and three flip-buttons. Demographic data were obtained from medical records. A functional evaluation using subjective shoulder value (SSV), visual analog scale (VAS), and disabilities of the arm, shoulder and hand (DASH) questionnaires was performed, and an evaluation of preoperative and postoperative comparative Zanca view images was performed. Factors associated with functional outcomes and radiological AC reduction were analyzed. Results A total of 83 patients completed follow-up and were included in the analysis. The mean SSV, VAS, and DASH scores were 92.8, 0.8, and 6.4, respectively. Patients who had complications experienced significantly worse functional outcomes (DASH: P=0.037). Suboptimal final AC reduction was observed in nine patients (11.1%), and significantly more frequently in patients older than 40 years (P=0.031) and in surgeries performed more than 7 days after injury (P=0.034). There were two reoperations (2.4%). Conclusions Anatomic CC fixation with a double clavicular tunnel and three flip-buttons leads to good functional outcomes, low complication rates, and high rates of optimal AC reduction. Conclusions Anatomic CC fixation with a double clavicular tunnel and three flip-buttons leads to good functional outcomes, low complication rates, and high rates of optimal AC reduction. Level of Evidence Level IV, case series.

Abstract Background Sarcoptic mange is one of the main parasitic diseases affecting the Iberian ibex Capra pyrenaica. Scabietic animals suffer a decline in body condition and reproductive fitness and in severe cases may die. Although several previous studies of the pathology of this disease and the physiological changes it produces in ibex have been carried out in recent years, our knowledge of the relationship between Sarcoptes scabiei and other ectoparasites of this host is still limited. Methods We analysed 430 Iberian ibex skin samples. Ectoparasites were removed, counted and identified. Mite (S. scabiei) numbers were obtained after digesting the skin samples in a 5% KOH solution. We modelled mite numbers in terms of host sex and age, site, year, season and the presence of other ectoparasites such as ticks and lice using generalized linear mixed models (GLMMs) and ectoparasite co-occurrence patterns using two different models: the probabilistic model species co-occurrence and the generalized linear latent variable model (GLLVM). Results The ectoparasite community was mainly composed of S. scabiei, six ticks (Haemaphysalis sulcata, Haemaphysalis punctata, Rhipicephalus bursa, Rhipicephalus turanicus, Dermacentor marginatus and Ixodes ricinus) and two lice (Bovicola crassipes and Linognathus stenopsis). Adult male ibex harboured more mites than females. Mite numbers varied greatly spatially and seasonally and increased with the presence of other parasites. Some positive co-occurrence relationships between pairs of different ectoparasites were observed, particularly between ticks. The presence of S. scabiei negatively affected lice and H. sulcata numbers. Conclusions Sarcoptic mange has spread above all in ibex populations in and around the Mediterranean Basin, where it is now found in almost a third of its host’s range. Mite numbers varied seasonally and spatially and were higher in male hosts. The presence of S. scabiei had a negative effect on lice numbers but favoured the presence of ticks. Graphical Abstract

BackgroundGender influences the health and social risks faced by individuals initiating drug injecting. Using mixed methods across three settings in North America, we investigated the gender composition of injection initiation events and the gendered risk environments in which they occurred.MethodsThe PReventing Injecting by Modifying Existing Responses (PRIMER) study pooled data from three prospective community-recruited cohorts of people who inject drugs (PWID) in San Diego, USA, Vancouver, Canada, and Tijuana, Mexico. A qualitative subsample provided narrative data on their experiences of, and the contexts for, injection initiation events. Guided by Rhodes' risk environment framework, we examined the gender composition of initiation events stratified by city, and analyzed qualitative data using abductive thematic analyses.ResultsAmong 2,622 PWID (Tijuana: n = 531; San Diego: n = 352; Vancouver: n = 1,739), 112 (4.3%) reported providing initiation assistance to injection-naïve individuals in the previous six months. The proportion of gender concordant (e.g., male-male) initiation pairs varied, (χ2 = 10.32, p

Human papillomavirus (HPV)-positive Head and Neck Squamous Cell Carcinomas (HNSCC) comprise a particular cancer entity traditionally associated with better clinical outcomes. Around 25% of HNSCC are HPV positive, HPV16 being the most prevalent type. Nevertheless, close to 30% of the HPV-positive patients have an unfavorable prognosis, revealing that this type of tumor exhibits great heterogeneity leading to different clinical behaviors. Efforts have been made to identify RNA molecules with prognostic value associated with the clinical outcome of patients with HPV-positive HNSCC, with the aim of identifying patients at high risk of metastasis, disease recurrence, and poor survival, who would require closer clinical follow-up and timely intervention. Moreover, the molecular identification of those HPV-positive HNSCC patients with good prognosis will allow the implementation of de-escalating therapeutic strategies, aiming to reduce side effects, resulting in a better quality of life. This review compiles a series of recent studies addressing different methodological and conceptual approaches aimed at searching for potential gene expression-based biomarkers associated with the prognosis of patients with HPV-positive HNSCC.

We introduce a novel method to derive rotation curves with light-day spatial resolution of the inner regions of lensed quasars. We aim to probe the kinematics of the inner part of the broad-line region by resolving the microlensing response—a proxy for the size of the emitting region—in the wings of the broad emission lines. Specifically, we assess the strength of the microlensing effects in the wings of the high-ionization lines Si iv and C iv across various velocity bins in five gravitationally lensed quasars: SDSS J1001+5027, SDSS J1004+4112, HE 1104−1805, SDSS J1206+4332, and SDSS J1339+1310. Using Bayesian methods to estimate the dimensions of the corresponding emission regions and adopting a Keplerian model as our baseline, we examine the consistency of the hypothesis of disklike rotation. Our results reveal a monotonic, smooth increase in microlensing magnification with velocity. The deduced velocity–size relationships inferred for the various quasars and emission lines closely conform to the Keplerian model of an inclined disk. This study provides the first direct evidence of Keplerian rotation in the innermost region of quasars across a range of radial distances spanning from ∼5 to 20 lt-days.

The reactivation of former rift systems and passive margins during tectonic inversion and their incorporation into fold-and-thrust belts result in significant structural differences not only between internal and external domains, but also along-strike. The Basque–Cantabrian and Asturian systems are among the best examples to address the role of along-strike changes in rift inheritance since they show a transition from salt to basement-inherited structures divided by a transition zone separating thick- from thin-skinned structural domains. While both domains have been widely described in the literature, the transfer system separating the two has not been sufficiently investigated due to poor seismic imaging and the lack of large-scale outcrops. This contribution aims to address the linkage between basement-controlled (i.e. thick-skinned) and salt-decoupled (i.e. thin-skinned) domains and to describe how deformation is accommodated in the transitional zone between these domains. An experimental programme based on analogue models has been designed that was inspired by the transition from the thin-skinned Basque–Cantabrian Pyrenees to the east to the thick-skinned Asturian Massif to the west. As observed in nature, experimental results show that oblique structures (at low angle with the shortening direction) form in the transitional domain, and their location depends on the linkage of the active structures occurring in both surrounding thick- and thin-skinned domains at different positions. Nevertheless, their orientation and evolution are controlled by the underlying decoupling horizon (i.e. salt). The deformation in the thick-skinned domain produces significant topography over a narrow deformation area due to the lack of effective decoupling levels. On the contrary, deformation in the thin-skinned domain is more distributed due to decoupling, resulting in a wider deformation area of less topography. As a result, syn-contractional sedimentation occurs mainly in the foreland basin in front of the thick-skinned domain, whereas it is observed in the foreland but also in piggyback basins in the thin-skinned domain.

An intense and long-lasting Saharan dust outbreak crossed the Iberian Peninsula (IP) from the southwest (SW) to the northeast (NE) from 25 March until 7 April 2021. This work aims to assess the optical and mass contribution of both fine and coarse dust particles along their transport. Five Iberian lidar stations were monitoring the transport and evolution of the Saharan dust particles, i.e. El Arenosillo/Huelva, Granada, Torrejón/Madrid and Barcelona in Spain, and Évora in Portugal. The particular meteorological conditions determined the aerosol scenario along the overall dust event, differing in the first part of the event (25–31 March), in which the strongest dust incidence occurred on 29–31 March at the south and central stations and 1 April at Barcelona, from the second one (1–7 April). The use of the two-step POLIPHON algorithm showed the relevance of using polarized lidar measurements for separating the aerosol properties of dust fine and coarse particles as an added value. Both the fine dust (Df) and coarse dust (Dc) components of the total particle backscatter coefficient (total dust, DD = Dc + Df) were separately derived. The dust plume was well-mixed with height and no significant differences were found in the vertical structure of both the Dc and Df particle backscatter coefficients. From the beginning of the dust outbreak until 1 April, the vertical Df / DD mass ratio was nearly constant in time at each station and also in altitude with values of ∼ 10 %. Moreover, the mean dust optical depth at 532 nm was decreasing along that dust pathway, reporting values from SW to NE stations of 0.34 at El Arenosillo/Huelva, 0.28 at Granada, 0.20 at Évora, 0.28 at Torrejón/Madrid, and 0.14 at Barcelona, although its Df / DD ratio remained almost constant (28 %–30 %). A similar pattern was found for the total dust mass loading and its Df / DD ratio, i.e. mostly decreasing mean mass values were reported, being constant in its Df / DD ratio (∼ 10 %) along the SW–NE dust pathway. In addition, the episode-mean centre-of-mass height increased with latitude overall, showing a high variability, being greater than 0.5 km at the southern sites (El Arenosillo/Huelva, Granada, Évora) and ∼ 1.0 km at Torrejón/Madrid and Barcelona. However, despite the relatively high intensity of the dust intrusion, the expected ageing of the dust particles was hardly observed, by taking into account the minor changes found in the contribution and properties of the coarse and fine dust particles. This is on the basis that the IP is relatively close to the Saharan dust sources and then, under certain dust transport conditions, any potential ageing processes in the dust particles remained unappreciated. The following must be highlighted: the different relative contribution of the fine dust particles to the total dust found for their optical properties (∼ 30 %) associated with the radiative effect of dust, with respect to that for the mass features (∼ 10 %) linked to air quality issues, along the overall dust event by crossing the IP.

Este estudio se centra en identificar los factores que influyen en la percepción de la calidad del consumidor en restaurantes de servicio a mesa en el pueblo mágico Real del Monte, Hidalgo, México. La metodología se basa en dos perspectivas, en primer lugar, en el análisis de los factores más importantes de los resultados de una encuesta de 22 ítems por medio de redes neuronales artificiales aplicada a 320 comensales y, en segundo lugar, en la aplicación de entrevistas semiestructuradas a ocho comensales. Los hallazgos muestran que los aspectos fundamentales que influyen en la percepción de los consumidores son la capacidad del personal para responder preguntas, la música de fondo, así como la calidad y el sabor de los alimentos.

The elbow is one of the most commonly dislocated joints. While conservative management is frequently performed for simple elbow dislocations, the importance of primary surgical treatment is still undetermined. However, promising results have been reached after surgical repair. We propose an arthroscopic surgical repair of the lateral ligament complex (LCL), performed with a horizontal suture and 2 Fibertak Knotless implants (Arthrex) placed on the LCL origin, one anterior and the other posterior. Operative treatment should be performed in patients with moderate and gross elbow laxity to avoid post-traumatic sequelae and decrease revision rates. Arthroscopic techniques create fewer complications. This procedure allows one to address intra-articular elbow joint pathology with less chance of wound complications and the ability to use bone anchors if desired.

Objetivo: Describir aspectos clínicos, microbiológicos y ecocardiográficos de endocarditis en un grupo específico de pacientes sin dispositivos intracardiacos ni cardiopatía estructural subyacente. Método: Estudio retrospectivo en el que se revisaron expedientes clínicos y reportes ecocardiográficos durante el periodo de 1997 a 2020. Se aplicaron los criterios modificados de Duke. Se describió la muestra por edad, sexo, enfermedad sistémica, vegetaciones y agente microbiológico. Se excluyeron pacientes con cardiopatía estructural o Libman-Sacks. Análisis estadístico: univariado expresado en frecuencias, utilizando medidas de dispersión y tendencia central. Resultados: Se revisaron 30,000 reportes ecocardiográficos, de los cuales solo 1350 tenían como motivo de envío endocarditis infecciosa, y de estos se seleccionaron 248 casos. La edad promedio fue de 48.1 ± 16.7 años. Hubo 140 hombres (56%) y 108 mujeres (44%). El signo ecocardiográfico más frecuente fue la vegetación, en 278 (93.60%), y la ubicación más común fue mitral (35.55%), con un número mayor de casos en el ventrículo derecho de lo esperado. La enfermedad sistémica más común fue la enfermedad renal, en 135 (41.08%). Se identificó un caso de Streptococcus thoraltensis no reportado previamente en México. Conclusiones: La presencia de endocarditis infecciosa ha aumentado debido a procedimientos invasivos intrahospitalarios y fármacos. Por su complejidad, los equipos multidisciplinarios son indispensables.

Introduction and objective: Teriflunomide is an oral immunomodulatory agent approved for the treatment of relapsing–remitting multiple sclerosis (RRMS). We examined teriflunomide outcomes in patients with RRMS under clinical practice conditions in Spain. Material and methods: Non-interventional, retrospective study at 15 sites in the Autonomous Region of Madrid and nearby regions. Effectiveness (relapses, EDSS, gadolinium-enhancing T1 lesions and new/enlarged T2-weighted lesions), safety (adverse events), and reasons for discontinuation during the 24 months after teriflunomide initiation were reported. Results: A total of 776 patients were included (mean [SD] age was 43.3 (9.8) years; 69.3% were female). Two-thirds (67.7%) of patients had received a prior treatment, with beta-interferons or glatiramer acetate (BRACE) as the most frequent (93.5%) treatment. After 24 months, teriflunomide significantly reduced the annualized relapse rate (ARR) by 72% (mean [95% confidence interval] 0.12 [0.10, 0.14] vs 0.43 [0.40, 0.47] at baseline; P

Brandy is a spirit obtained from distilled wine that has an alcohol content equal to or greater than 36 % ABV (Alcohol by Volume). It undergoes an ageing process in oak wood casks with a capacity of up to 1000 L for a minimum of six months. During this process, a series of physicochemical and sensory changes take place that confer the initial wine distillate with a series of improvements to its sensory profile. Such changes are mainly determined by the intrinsic characteristics of the wood and by those associated with the manufacturing process of the casks. The previous use of the casks, ageing time and the alcoholic strength of the wine distillate are also important factors, among others. The casks, which will have previously contained some type of Sherry wine (such as Fino, Amontillado, Oloroso and Pedro Ximénez), are known as Sherry Casks® and they must be used in the production of Brandy de Jerez. During the ageing of Brandy de Jerez, Sherry Casks® contribute to the final brandy via the compounds that are both inherent to the wood they are made of and from the wine that they initially contained and that were retained in the wood pores. The alcohol content of the wine distillate to be aged significantly affects not only the quality of the brandy, but also the financial cost of the process. This study aimed to determine the influence on brandy of the alcoholic strength of wine distillates aged in static ageing systems using Sherry Casks®. Specifically, we assessed the physicochemical composition and sensory profile of Brandy de Jerez made from wine distillates with three different alcoholic strengths (40 %, 55 % and 68 % ABV) and aged for 24 months. The Brandy de Jerez with lower alcoholic strengths (40 % - 55 % ABV) were found to contain a higher concentration of polyphenolic compounds deriving from the wood as well as from the constituents of the cask-seasoning Sherry wine. The brandies with higher alcoholic strengths exhibited a marked colour change, while the 40 % and 55 % ABV brandies were perceived to have the best sensory characteristics.

While several technological solutions are available for older adults to improve their wellbeing and quality of life, little is known about the gaps between the needs, provided solutions, and their adoption from a more pragmatic perspective. This paper reports on reviewing existing technological solutions for older adults, which span the work life, life in the community, and wellbeing at home. We analyzed 50 different solutions to uncover both negative and positive features of these solutions from the perspective of the impact of technology adoption on the quality of life of older adults. Our approach harnesses holistic reasoning to determine the most suitable technologies available today and provides suggestions for improvement toward designing and implementing better solutions.

Cryptic faults concern earthquake scientists, since they pose a hidden seismic potential which is hard to identify. To address this, the authors here study off-fault deformed geomorphic markers such as marine terraces using high-resolution LiDAR topography, optical dating of sediments and space geodetic observations.

Nowadays, metaheuristic algorithms have been applied to optimize last lower-surface models. Also, the last lower-surface model has been adjusted through the computational algorithms to perform custom shoe lasts. Therefore, it is necessary to implement nature-inspired metaheuristic algorithms to perform the adjustment of last lower-surface model to the footprint topography. In this study, a metaheuristic genetic algorithm is implemented to adjust the last lower surface model to the footprint topography. The genetic algorithm is constructed through an objective function, which is defined through the last lower Bezier model and footprint topography, where a mean error function moves the last lower surface toward the footprint topography through the initial population. Also, the search space is deduced from the last lower surface and footprint topography. In this way, the genetic algorithm performs explorations and exploitations to optimize a Bezier surface model, which generates the adjusted last lower surface, where the surface is recovered via laser line scanning. Thus, the metaheuristic algorithm enhances the last lower-surface adjustment to improve the custom last manufacture. This contribution is elucidated by a discussion based on the proposed metaheuristic algorithm for surface model adjustment and the optimization methods implemented in recent years. [ABSTRACT FROM AUTHOR]

To establish classifications and to obtain pre- and post-operative information on patient-specific alignments, it is necessary to measure different angular values accurately and precisely, mainly on weight-bearing, full-length anteroposterior X-rays of the lower limbs (LLRs). This study evaluated angular measurements’ validity and absolute reliability on LLRs with a self-developed, computer-aided measurement system (TraumaMeter v.873). Eight independent observers measured the preoperative mechanical hip-knee-ankle (mHKA) angle of 52 lower extremities (26 cases) in a blinded fashion on three occasions separated by two weeks. We obtained an intra-observer mean bias error (MBE) of 0.40°, a standard deviation (SD) of 0.11°, and a 95% confidence interval (CI) of 0.37°–0.43°. We also obtained an inter-observer MBE of 0.49°, an SD of 0.15°, and a 95% C of 0.45°–0.53°. The intra-observer MBE for the measurement pair between the second and the first measurement round (T2T1) was 0.43°, the SD was 0.13°, and the 95% CI was 0.39°–0.47°; the MBE between the third and the second round (T3T2) was 0.37°, with an SD of 0.10° and a 95% CI of 0.34°–0.40°; and the MBE between the third and the first round (T3T1) was 0.40°, with an SD of 0.10° and a 95% CI of 0.37°–0.43°. The interobserver MBE for the first round of measurements was 0.52°, with an SD of 0.16° and a 95% CI of 0.48°–0.56°; the MBE for the second round was 0.50°, with an SD of 0.15° and a 95% CI of 0.46°–0.54°; and the MBE for the third round was 0.46°, with an SD of 0.14° and a 95% CI of 0.42°–0.50°. There were no statistically significant differences in the inter-observer errors for the three tests. In the case of the intra-observer analysis, there were differences between T2T1 and between T3T2, but these differences were minimal, with no overlaps in the lower or upper values, respectively, of the confidence intervals. These results led us to conclude that the TraumaMeter v.873 software extension for measuring lower-limb angles in LLRs is an accurate tool with low intra- and inter-observer variability.

We propose and discuss a new experimental approach to measure the centroid shift induced by gravitational microlensing in the images of lensed quasars (astrometric microlensing). Our strategy is based on taking the photocenter of a region in the quasar large enough as to be insensitive to microlensing as reference to measure the centroid displacement of the continuum. In this way, single-epoch measurements of astrometric microlensing can be performed. Using numerical simulations, we show that, indeed, the centroid shift monotonically decreases as the size of the emitting region increases, and only for relatively large regions, like the broad line region (BLR), does the centroid shift become negligible. This opens interesting possibilities to study the stratification of the different emitters in the accretion disk and the BLR. We estimate the amplitude of the centroid shifts for 79 gravitationally lensed images and study more thoroughly the special cases Q2237+030 A, RXJ1131-1231 A, PG1115+080 A2, and SDSS J1004+4112 A. We propose to use spectro-astrometry to simultaneously obtain the photocenters of the continuum and of different emission line regions since, with the precision of forthcoming instruments, astrometric microlensing by ∼1 M _⊙ mass microlenses may be detected in many quasar lensed images. When we consider more massive micro/millilenses, M ≳ 10 M _⊙ , often proposed as the constituents of dark matter, the BLR becomes sensitive to microlensing and can no longer be used as a positional reference to measure centroid shifts. Differential microlensing between the images of a lensed quasar along several epochs should be used instead.

In the human glucose-insulin regulatory system, diverse metabolic issues can arise, including diabetes type I and type II, hyperinsulinemia, hypoglycemia, etc. Therefore, the analysis and characterization of such a biological system is a must. It is well known that mathematical models are an excellent option to study and predict natural phenomena to some extent. On the other hand, fractional-order calculus provides a generalization of derivatives and integrals to arbitrary orders giving us a framework to add memory properties and an extra degree of freedom to the mathematical models to approximate real-world phenomena with higher accuracy. In this work, we introduce a fractional-order version of a mathematical model of the glucose-insulin regulatory system. Using the fractional-order Caputo derivative, we can investigate different concentration rates among insulin, glucose, and healthy beta cells. Additionally, the model incorporates two time-lags to represent the elapsed time in insulin secretion in response to blood glucose level and the delay in glucose drop due to increased insulin concentration. Analytical results of the equilibrium points and their corresponding stability are given. Numerical results, including phase portraits and bifurcation diagrams, reveal that the fractional-order increases the chaotic regions, leading to potential metabolic problems. Vice versa, the system seems to work correctly when the behavior evolves to periodic windows.