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ABSTRACT Introduction and objectives: The optimal treatment of nonculprit angiographic intermediate lesions (diameter stenosis 40%-69%) in patients with ST-segment elevation myocardial infarction (STEMI) is still unknown. Lesions with fractional flow reserve (FFR) ≤ 0.80 are indicative of ischemia and benefit from revascularization. However, lesions with FFR > 0.80 and optical coherence tomography (OCT) findings of vulnerability have been hypothesized to cause adverse events during follow-up. The study aims to compare the efficacy of a preventive treatment with stent implantation plus optimal medical therapy vs optimal medical therapy alone for nonculprit intermediate lesions with FFR > 0.80 and OCT findings of plaque vulnerability in STEMI patients at 4 years of follow-up. Methods: This parallel-group, multicenter, controlled, single-blind, and 1:1 randomized trial will enroll a total of 600 STEMI patients with ≥ 1 intermediate nonculprit lesions with FFR > 0.80 and OCT findings of plaque vulnerability. The primary endpoint is target vessel failure, defined as the composite of cardiac death, target vessel myocardial infarction, or target vessel revascularization. The study will include a parallel registry of patients with FFR > 0.80 but without OCT findings of vulnerability. Vulnerable plaques are defined as lipid-rich fibroathermas with plaque burden ≥ 70% and a thin fibrous cap (≤ 80 μm). Results: The VULNERABLE trial will reveal the role of preventive treatment with stent implantation for nonculprit and functionally nonsignificant vulnerable plaques in STEMI patients. Conclusions: This is the first randomized trial of OCT-guided treatment of vulnerables plaques. Registered at ClinicalTrials.gov (NCT05599061).

Introducción y objetivos: El tratamiento óptimo de las lesiones angiográficas intermedias (diámetro de estenosis 40-69%) no culpables en pacientes con infarto agudo de miocardio con elevación del segmento ST (IAMCEST) está por determinar. La reserva fraccional de flujo (RFF) permite diagnosticar lesiones causantes de isquemia (RFF ≤ 0,80) que se benefician de una revascularización. No obstante, las lesiones con RFF > 0,80 y criterios de vulnerabilidad por tomografía de coherencia óptica (OCT) también se ha hipotetizado que pueden causar eventos adversos en el seguimiento. El objetivo es comparar la eficacia del tratamiento preventivo con implantación de stent más tratamiento médico óptimo de lesiones intermedias no culpables con RFF > 0,80 y características de placa vulnerable frente a solo tratamiento médico óptimo en pacientes con IAMCEST a 4 años de seguimiento. Métodos: Estudio de grupos paralelos, multicéntrico, controlado, aleatorizado 1:1 y simple ciego. Se incluirán 600 pacientes con IAMCEST y al menos una lesión intermedia no culpable que presenten RFF > 0,80 y características de placa vulnerable por OCT. El objetivo primario se define como fallo del vaso diana, compuesto de muerte cardiaca, infarto del vaso diana y necesidad de revascularización del vaso diana. El estudio incluye un registro paralelo para pacientes con RFF > 0,80 sin características de placa vulnerable. Se define placa vulnerable como fibroateromas lipídicos con carga de placa ≥ 70% y capa fibrosa fina (≤ 80 µm). Resultados: El estudio VULNERABLE permitirá conocer el papel del tratamiento preventivo con stent de placas vulnerables no culpables funcionalmente no significativas en pacientes con IAMCEST. Conclusiones: Se trata del primer estudio aleatorizado para el tratamiento de placas vulnerables guiado por OCT. Registrado en ClinicalTrials.gov (NCT05599061).

Background: Longitudinal changes in gut microbiome and inflammation may be involved in the evolution of atherosclerosis after an acute coronary syndrome (ACS). We aimed to characterize repeated profiles of gut microbiota and peripheral CD4+ T lymphocytes during the first year after an ACS, and to address their relationship with atherosclerotic plaque changes. Methods: Over one year we measured the microbiome, peripheral counts of CD4+ T populations and cytokines in 67 patients shortly after a first ACS. We compared baseline measurements to those of a matched population of 40 chronic patients. A subgroup of 20 ACS patients underwent repeated assessment of fibrous cap thickness (FCT) of a non-culprit lesion. Results: At admission, ACS patients showed gut dysbiosis compared with the chronic group, which was rapidly reduced and remained low at 1-year. Also, their Th1 and Th2 CD4+ T counts were increased but decreased over time. The CD4+ T counts were related to ongoing changes in gut microbiome. Unsupervised clustering of repeated CD4+ Th0, Th1, Th2, Th17 and Treg counts in ACS patients identified two different cell trajectory patterns, related to cytokines. The group of patients following a high-CD4+ T cell trajectory showed a one-year reduction in their FCT [net effect = -24.2 µm; p = 0.016]. Conclusions: Patients suffering an ACS show altered profiles of microbiome and systemic inflammation that tend to mimic values of chronic patients after 1-year. However, in one-third of patients, this inflammatory state remains particularly dysregulated. This persistent inflammation is likely related to plaque vulnerability as evident by fibrous cap thinning (Clinical Trial NCT03434483).

Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P

Gait monitoring using hip joint angles offers a promising approach for person identification, leveraging the capabilities of smartphone inertial measurement units (IMUs). This study investigates the use of smartphone IMUs to extract hip joint angles for distinguishing individuals based on their gait patterns. The data were collected from 10 healthy subjects (8 males, 2 females) walking on a treadmill at 4 km/h for 10 min. A sensor fusion technique that combined accelerometer, gyroscope, and magnetometer data was used to derive meaningful hip joint angles. We employed various machine learning algorithms within the WEKA environment to classify subjects based on their hip joint pattern and achieved a classification accuracy of 88.9%. Our findings demonstrate the feasibility of using hip joint angles for person identification, providing a baseline for future research in gait analysis for biometric applications. This work underscores the potential of smartphone-based gait analysis in personal identification systems.

The main purpose of anti-forensic computer techniques, in the broadest sense, is to hinder the investigation of a computer attack by eliminating traces and preventing the collection of data contained in a computer system. Nowadays, cyber-attacks are becoming more and more frequent and sophisticated, so it is necessary to understand the techniques used by hackers to be able to carry out a correct forensic analysis leading to the identification of the perpetrators. Despite its importance, this is a poorly represented area in the scientific literature. The disparity of the existing works, together with the small number of articles, makes it challenging to find one’s way around the vast world of computer forensics. This article presents a comprehensive review of the existing scientific literature on anti-forensic techniques, mainly DFIR (digital forensics incident response), organizing the studies according to their subject matter and orientation. It also presents key ideas that contribute to the understanding of this field of forensic science and details the shortcomings identified after reviewing the state of the art.

Clot formation is a crucial process that prevents bleeding, but can lead to severe disorders when imbalanced. This process is regulated by the coagulation cascade, a biochemical network that controls the enzyme thrombin, which converts soluble fibrinogen into the fibrin fibers that constitute clots. Coagulation cascade models are typically complex and involve dozens of partial differential equations (PDEs) representing various chemical species' transport, reaction kinetics, and diffusion. Solving these PDE systems computationally is challenging, due to their large size and multi-scale nature. We propose a multi-fidelity strategy to increase the efficiency of coagulation cascade simulations. Leveraging the slower dynamics of molecular diffusion, we transform the governing PDEs into ordinary differential equations (ODEs) representing the evolution of species concentrations versus blood residence time. We then Taylor-expand the ODE solution around the zero-diffusivity limit to obtain spatiotemporal maps of species concentrations in terms of the statistical moments of residence time, [Formula: see text], and provide the governing PDEs for [Formula: see text]. This strategy replaces a high-fidelity system of N PDEs representing the coagulation cascade of N chemical species by N ODEs and p PDEs governing the residence time statistical moments. The multi-fidelity order (p) allows balancing accuracy and computational cost providing a speedup of over N/p compared to high-fidelity models. Moreover, this cost becomes independent of the number of chemical species in the large computational meshes typical of the arterial and cardiac chamber simulations. Using a coagulation network with N = 9 and an idealized aneurysm geometry with a pulsatile flow as a benchmark, we demonstrate favorable accuracy for low-order models of p = 1 and p = 2. The thrombin concentration in these models departs from the high-fidelity solution by under 20% (p = 1) and 2% (p = 2) after 20 cardiac cycles. These multi-fidelity models could enable new coagulation analyses in complex flow scenarios and extensive reaction networks. Furthermore, it could be generalized to advance our understanding of other reacting systems affected by flow.

Los autores dan a conLos autores dan a conocer una nueva inscripción procedente de Irni, gravada sobre una uncia, con el nombre del edil que ha garantizado su peso de acuerdo con las atribuciones que le confiere el artículo 19 de la lex Irnitana. Este nuevo documento amplia el ya importante corpus epigráfico del municipio Flavio Irnitano, formado con inscripciones procedentes del propio yacimiento del Molino del Postero y de otros lugares próximos, que, sin duda, formarían parte del territorium de Irni.

IntroductionClostridioides difficile infection (CDI) is the main cause of nosocomial diarrhoea in developed countries. Recurrent CDI (R-CDI), which affects 20%-30% of patients and significantly increases hospital stay and associated costs, is a key challenge. The main objective of this study was to explore the role of the microbiome and calprotectin levels as predictive biomarkers of R-CDI.MethodsWe prospectively (2019-2021) included patients with a primary episode of CDI. Clinical data and faecal samples were collected. The microbiome was analysed by sequencing the hypervariable V4 region of the 16S rRNA gene on an Illumina Miseq platform.ResultsWe enrolled 200 patients with primary CDI, of whom 54 developed R-CDI and 146 did not. We analysed 200 primary samples and found that Fusobacterium increased in abundance, while Collinsella, Senegalimassilia, Prevotella and Ruminococcus decreased in patients with recurrent versus non-recurrent disease. Elevated calprotectin levels correlated significantly with R-CDI (p=0.01). We built a risk index for R-CDI, including as prognostic factors age, sex, immunosuppression, toxin B amplification cycle, creatinine levels and faecal calprotectin levels (overall accuracy of 79%).DiscussionCalprotectin levels and abundance of microbial genera such as Fusobacterium and Prevotella in primary episodes could be useful as early markers of R-CDI. We propose a readily available model for prediction of R-CDI that can be applied at the initial CDI episode. The use of this tool could help to better tailor treatments according to the risk of R-CDI.

Nowadays, the study of ports in Hispania has a firmly established line of research highlighting the port configuration of numerous Atlantic and Mediterranean cities. Within this context, along the coasts of the Iberian Peninsula —as well as in the course of the main rivers— the port settlements that mark the water from the Mediterranean to the Cantabrian Sea have a series of structures or environments whose architectural elements seem to follow standard patterns in their structural systems and location that are perpetuated throughout their evolution. The common need to solve the various problems caused by maritime traffic and port activity linked to the commercial networks of an increasingly complex provincialized imperial economy seems to lie in their endowment.

Estuaries are excellent environments for identifying pollution episodes that have affected river basins, as their sediments are the final destination of some of the pollutants. This paper studies the geochemical evolution of five elements (As, Co, Cu, Pb, Zn) in a core extracted from the middle estuary of the Tinto River (SW Spain). The results are based on facies interpretation, ICP atomic emission spectrometry analysis, the application of a regional background to obtain the geoaccumulation index and dating. The main objective of this communication is the detection of natural or anthropogenic pollution episodes in the middle estuary of the Tinto River (SW Spain). Four pollution episodes have been detected: (1) ~5.8 cal. kyr BP, probably caused by natural acid rock drainage processes derived from the oxidation of the Iberian Pyritic Belt deposits found in its drainage basin; (2) 4.7–4.5 kyr BP, coming from the first mining activities and characterized by a significant increase in the concentrations of the five elements analyzed; (3) 1850–1960 interval, coinciding with intensive mining and characterized by increasing values of As and, to a lesser extent, Pb (intensive mining); and (4) the second half of the 20th century, with high element concentrations from mining and industrial effluents. All episodes show an increase in their geochemical classes deduced from the geoaccumulation index. This communication can serve as an example for assessing the impact of different types of pollution in estuarine environments.

Abstract Background Primary prevention trials have demonstrated that the traditional Mediterranean diet is associated with a reduction in cardiovascular mortality and morbidity. However, this benefit has not been proven for secondary prevention after an acute coronary syndrome (ACS). We hypothesized that a high-intensity Mediterranean diet intervention after an ACS decreases the vulnerability of atherosclerotic plaques by complex interactions between anti-inflammatory effects, microbiota changes and modulation of gene expression. Methods The MEDIMACS project is an academically funded, prospective, randomized, controlled and mechanistic clinical trial designed to address the effects of an active randomized intervention with the Mediterranean diet on atherosclerotic plaque vulnerability, coronary endothelial dysfunction and other mechanistic endpoints. One hundred patients with ACS are randomized 1:1 to a monitored high-intensity Mediterranean diet intervention or to a standard-of-care arm. Adherence to diet is assessed in both arms using food frequency questionnaires and biomarkers of compliance. The primary endpoint is the change (from baseline to 12 months) in the thickness of the fibrous cap of a non-significant atherosclerotic plaque in a non-culprit vessel, as assessed by repeated optical coherence tomography intracoronary imaging. Indices of coronary vascular physiology and changes in gastrointestinal microbiota, immunological status and protein and metabolite profiles will be evaluated as secondary endpoints. Discussion The results of this trial will address the key effects of dietary habits on atherosclerotic risk and will provide initial data on the complex interplay of immunological, microbiome-, proteome- and metabolome-related mechanisms by which non-pharmacological factors may impact the progression of coronary atherosclerosis after an ACS. Trial registration ClinicalTrials.gov NCT03842319 . Registered on 13 May 2019

The arrhythmic substrate of ventricular tachycardias in many structural heart diseases is located in the epicardium, often resulting in poor outcomes with currently available therapies. Cardiosphere-derived cells (CDCs) have been shown to modify myocardial scarring. A total of 19 Large White pigs were infarcted by occlusion of the mid-left anterior descending coronary artery for 150 min. Baseline cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement sequences was obtained 4 weeks post-infarction and pigs were randomized to a treatment group (intrapericardial administration of 300,000 allogeneic CDCs/kg), (n = 10) and to a control group (n = 9). A second CMR and high-density endocardial electroanatomical mapping were performed at 16 weeks post-infarction. After the electrophysiological study, pigs were sacrificed and epicardial optical mapping and histological studies of the heterogeneous tissue of the endocardial and epicardial scars were performed. In comparison with control conditions, intrapericardial CDCs reduced the growth of epicardial dense scar and epicardial electrical heterogeneity. The relative differences in conduction velocity and action potential duration between healthy myocardium and heterogeneous tissue were significantly smaller in the CDC-treated group than in the control group. The lower electrical heterogeneity coincides with heterogeneous tissue with less fibrosis, better cardiomyocyte viability, and a greater quantity and better polarity of connexin 43. At the endocardial level, no differences were detected between groups. Intrapericardial CDCs produce anatomical and functional changes in the epicardial arrhythmic substrate, which could have an anti-arrhythmic effect.

El presente artículo tiene como propósito realizar una aproximación a la realidad arquitectónica y al fenómeno urbano desarrollado en la ciudad de Huelva entre los siglos VIII y VI a.C. Esta investigación parte de la consulta de los resultados de las diferentes intervenciones arqueológicas realizadas en lo que conocemos como la Zona Arqueológica de Huelva, destacando aquellas que han sido trascendentales para el desarrollo de esta línea de investigación. Asimismo, para enriquecer y proporcionar nuevas perspectivas al estado de la investigación, hemos propuesto el SIG como herramienta de apoyo por su capacidad para interconectar, gestionar y analizar toda la información relativa a nuestro caso de estudio. Así como un nuevo medio por el cual difundir virtualmente el patrimonio protohistórico y punto de partida para avanzar en la investigación en el futuro.

La vivienda urbana puede aportar información de una enorme relevancia para la reflexión sobre el pasado romano al dar cabida al planteamiento y resolución de cuestiones de muy diversa naturaleza sobre la sociedad. El presente trabajo contempla el estudio arquitectónico y funcional de la Domus de Peristilo de la ciudad hispanorromana de Arucci (Aroche, Huelva), con el objetivo de presentar una panorámica general sobre la vivienda y la arquitectura doméstica de la ciudad, pero también sobre el marco urbano, económico, político, social y cultural en el que se inserta. Con ello, trataremos de conciliar la situación dispar que caracteriza a este tipo de estudios, tradicionalmente relegados a un segundo plano en favor del análisis de las grandes construcciones públicas, a la par que subrayaremos la necesidad de verlos incrementados en un futuro a corto y medio plazo.

El edificio termal de la ciudad romana de Arucci se constituye como un interesante conjunto arquitectónico dentro de esta categoría de edificios públicos en el contexto hispano. Ubicado en una de las cotas más altas de la ciudad, este espacio dedicado al baño ha podido ser delimitado parcialmente a lo largo de diversas campañas de excavación y prospecciones geofísicas enmarcadas en distintos proyectos de investigación. Los resultados de las últimas actividades vienen a sumarse a los ya conocidos, lo que ha permitido individualizar numerosas dependencias, piscinae, latrinae, apodyterium, cisternae, etc., que nos aproximan a conocer, de manera más precisa, la funcionalidad y el funcionamiento de las termas en su época de actividad. Desde el punto de vista cronológico, el edificio está estructurado en dos ambientes, construyéndose el primero en un momento previo a la segunda mitad del siglo I d.C.; y el segundo, muy probablemente enmarcado en el impulso monumentalizador que sufre la ciudad en época Flavia, manteniendo su uso hasta su abandono en el primer cuarto del siglo III d.C.

La Baeturia Céltica ha sido estudiada en innumerables ocasiones y, en tiempos recientes, son numerosas las investigaciones basadas en la aplicación de nuevas tecnologías que se han llevado a cabo, aportando datos de gran interés. Por ello, el presente estudio analiza mediante la aplicación de SIG los modelos de poblamiento y explotación de recursos de los asentamientos prerromanos de la Rivera del Chanza y sus transformaciones durante el proceso de conquista y colonización romana del territorio, cuya máxima expresión sería la fundación de la ciudad de Arucci. Todo ello nos permitirá saber más sobre si estas poblaciones presentaban, o no, relaciones de subordinación, si la conquista romana pudo aprovechar la realidad social previa a su favor, qué papel desempeñan los recursos naturales del entorno en todo ello o cómo se traducen estas cuestiones en el modelo de poblamiento.

With ever-rising population comes a corresponding rise in people with mobility issues who have difficulty handling tasks in their daily lives. Such persons could benefit significantly from an active movement assistance device. This paper presents the design of a lower-limb exosuit designed to provide the wearer with useful gait assistance. While exoskeletons have existed for a while, soft exoskeletons or exosuits are relatively new. One challenge in the design of a gait-assistance device is the reduction of device weight. In order to facilitate this, the concept of kinematic synergies is implemented to reduce the number of actuators. In this prototype, the exosuit can actuate the hip, ankle, and knee of both legs using just one single motor, and a transmission system consisting of gears and clutches. The implementation of these synergies and their advantages are detailed in this paper, as well as preliminary tests to assess performance. This was performed by testing the exosuit worn by a subject on a treadmill while taking EMG readings and measuring cable tension produced. Significant reductions by up to 35% in certain muscle activations were observed, demonstrating the validity of this prototype for gait assistance.

Ageing results in the eventual loss of muscle mass and strength, joint problems, and overall slowing of movements, with a greater risk of suffering falls or other such accidents. The use of gait assistance exoskeletons can help in the active aging of this segment of the population. Given the user specificity of the mechanics and control these devices need, the facility used to test different design parameters is indispensable. This work deals with the modeling and construction of a modular test bench and prototype exosuit to test different mounting and control schemes for a cable-driven exoskeleton or exosuit. The test bench allows the experimental implementation of postural or kinematic synergies to assist multiple joints by using only one actuator and the optimization of the control scheme to better adapt to the characteristics of the specific patient. The design is open to the research community and it is expected to improve the design of cable-driven systems for exosuits.

The problem of digital identity acquires more relevance every day in the eyes of a society that spends more and more time connected to the Internet. It has evolved throughout its history to reach a decentralized model known as Self-Sovereign Identity (SSI), which finds its natural tools in the blockchain technology and Zero-Knowledge Proofs (ZKPs). ZKPs, in this context, allow users to prove that their credentials are legitimate without revealing more information than is strictly necessary, and constitute one of the most promising areas of applied cryptography. In this work, an application is developed for the study of Zero-Knowledge Proof methods and, specifically, in their application for authentication in public-private key encryption systems. It focuses on the study of three ZKP protocols (Feige-Fiat-Shamir, Guillou-Quisquater, and Schnorr, which rely on the problems of large number factorizations and discrete logarithms for security) in the practical use-case where a prover wants to demonstrate knowledge of a private key for a public key without revealing the key itself. The application allows the user to modify the necessary parameters in each method to achieve a better understanding of their role in their safety and efficiency. Several types of attacks are carried out against the above-mentioned protocols to analyze their degree of security and what recommendations can be made to improve it.

Noninvasive staging of decompensated cirrhosis is an unmet clinical need. The aims of this study were to characterize and validate a novel microRNA (miRNA) signature to stage decompensated cirrhosis and predict the portal pressure and systolic cardiac response to nonselective beta‐blockers (NSBBs). Serum samples from patients with decompensated cirrhosis (n = 36) and healthy controls (n = 36) were tested for a novel signature of five miRNAs (miR‐452‐5p, miR‐429, miR‐885‐5p, miR‐181b‐5p, and miR‐122‐5p) identified in the secretome of primary human hepatocytes and for three miRNAs (miR‐192‐5p, miR‐34a‐5p, and miR‐29a‐5p) previously discovered as biomarkers of chronic liver disease. All patients had ascites, which was refractory in 18 (50%), and were placed on NSBBs for variceal bleeding prophylaxis. In all patients, serum miRNAs, hepatic venous pressure gradient, and an echocardiogram study were performed before and 1 month after NSBBs. Patients with cirrhosis had lower serum levels of miR‐429, miR‐885‐5p, miR‐181b‐5p, miR‐122‐5p, miR‐192‐5p, and miR‐29a‐5p (P

Injection attacks against web applications are still frequent, and organizations like OWASP places them within the Top Ten of security risks to web applications. The main goal of this work is to contribute to the community with the design of an effective protection of web applications against common injection attacks. Our proposal is a validation filter of input fields that is based on OWASP Stinger, a set of regular expressions, and a sanitization process. It validates both fundamental characters (letters, numbers, dot, dash, question marks, and exclamation point) and complex statements (JSON and XML files) for each field. The procedure of deploying the proposed filter is detailed, specifying the sections and contents of the configuration file. In addition, the infrastructure for running the tests is described, including the setting of an attack tool, and the implementation of a controller. The attack tool is used as a security scanner for common injection attacks, and the controller is developed for routing the requests in two steps; first a request is addressed to the filter, and if it is valid, it will redirect to the web application itself. The proposal filter has been tested on three public as well as on a real private web application. An accuracy of 98,4% and an average processing time of 50 ms are achieved, based on wich it is possible to conclude the proposed filter is highly reliable and does not require additional computational resources.

Organizations use Active Directory Windows service to authenticate users in a network with the extended Kerberos Authentication protocol. Therefore, it is necessary to investigate its resistance to the different types of attacks it can suffer, the best way to detect them and to parameterize it to mitigate the effects of the attacks. This work analyzes the main Kerberos attacks in Active Directory Windows networks, inherent in the design of the protocol and not resolved. For each attack the objective is studied, implementation is developed in a virtual laboratory and detection is analyzed, proposing measures for mitigation and response. Subsequently, they are discussed in a general way and the results of the attacks are analyzed according to some parameters. As conclusions of the work carried out, it should be noted that although the attacks are mostly difficult to implement, their detection is even more complicated, and the damage is very severe so it’s necessary to continuously monitor the logs in these environments to detect them and taking into account strict recommendations for mitigation and response.

Abstract Despite many cardioprotective interventions have shown to protect the heart against ischemia/reperfusion injury in the experimental setting, only few of them have succeeded in translating their findings into positive proof-of-concept clinical trials. Controversial and inconsistent experimental and clinical evidence supports the urgency of a disruptive paradigm shift for testing cardioprotective therapies. There is a need to evaluate experimental reproducibility before stepping into the clinical arena. The CIBERCV (acronym for Spanish network-center for cardiovascular biomedical research) has set up the “Cardioprotection Large Animal Platform” (CIBER-CLAP) to perform experimental studies testing the efficacy and reproducibility of promising cardioprotective interventions based on a pre-specified design and protocols, randomization, blinding assessment and other robust methodological features. Our first randomized, control-group, open-label blinded endpoint experimental trial assessing local ischemic preconditioning (IPC) in a pig model of acute myocardial infarction (n = 87) will be carried out in three separate sets of experiments performed in parallel by three laboratories. Each set aims to assess: (A) CMR-based outcomes; (B) histopathological-based outcomes; and (C) protein-based outcomes. Three core labs will assess outcomes in a blinded fashion (CMR imaging, histopathology and proteomics) and 2 methodological core labs will conduct the randomization and statistical analysis.

Objective One of the challenges in hypertrophic cardiomyopathy (HCM) is to determine the pathogenicity of genetic variants and to establish genotype/phenotype correlations. This study aimed to: (1) demonstrate that MYBPC3 c.2149–1G>A is a founder pathogenic variant, (2) describe the phenotype and clinical characteristics of mutation carriers and (3) compare these patients with those with the most frequent pathogenic HCM variants: MYBPC3 p.Arg502Trp/Gln.Methods We reviewed genetic tests performed in HCM probands at our institution. We carried out transcript analyses to demonstrate the splicing effect, and haplotype analyses to support the founder effect of MYBPC3 c.2149–1G>A. Carriers with this mutation were compared with those from MYBPC3 p.Arg502Trp/Gln in terms of presentation features, imaging and outcomes.Results MYBPC3 c.2149–1G>A was identified in 8 of 570 probands and 25 relatives. Penetrance was age and sex dependent, 50.0% of the carriers over age 36 years and 75.0% of the carriers over 40 years showing HCM. Penetrance was significantly higher in males: in carriers older than 30 years old, 100.0% of males vs 50.0% of females had a HCM phenotype (p=0.01). Males were also younger at diagnosis (32±13 vs 53±10 years old, pA resulted in an abnormal transcript that led to haploinsufficiency and was segregated in two haplotypes. However, both came from one founder haplotype. Affected carriers showed a better functional class and higher left ventricular ejection fraction (LVEF) than patients with MYBPC3 p.Arg502Trp/Gln (pA splicing variant is a founder mutation. Affected males show an early onset of HCM and with higher penetrance than women. Carriers show better functional class and higher LVEF than MYBPC3 p.Arg502Trp/Gln carriers, but a similar rate of major adverse outcomes.

Older adults (aged 55 years and above) have greater difficulty carrying out activities of daily living than younger adults (aged 25–55 years). Although age-related changes in human gait kinetics are well documented in qualitative terms in the scientific literature, these differences may be quantified and analyzed using the analysis of motor control strategies through kinetic synergies. The gaits of two groups of people (older and younger adults), each with ten members, were analyzed on a treadmill at a constant controlled speed and their gait kinetics were recorded. The decomposition of the kinetics into synergies was applied to the joint torques at the hip, knee, and ankle joints. Principal components determined the similarity of the kinetic torques in the three joints analyzed and the effect of the walking speed on the coordination pattern. A total of three principal components were required to describe enough information with minimal loss. The results suggest that the older group showed a change in coordination strategy compared to that of the younger group. The main changes were related to the ankle and hip torques, both showing significant differences (p-value <0.05) between the two groups. The findings suggest that the differences between the gait patterns of the two groups were closely related to a reduction in ankle torque and an increase in hip torque. This change in gait pattern may affect the rehabilitation strategy used when designing general-purpose rehabilitation devices or rehabilitation/training programs for the elderly.

The strategies for thermal regulation and environmental control found in nature are countless. In this article, a parallelism between animals and building energy systems is defined in order to identify and emphasize the immediate opportunities that biomimicry offers for future research. The motivation was the need to find alternative solutions to tackle problems mainly in the efficiency of heating, ventilation and cooling systems. Due to the wide range of possibilities offered by animals, this study is largely limited to the strategies that cold-blooded animals have developed through evolutionary adaptation to the environment.The method used for the analysis is based on a solution-based approach. Firstly, different animal thermoregulation strategies are defined (biological domain). Then the strategy is analyzed and classified into three categories. This classification is essential in order to formulate the parallelism with building systems (transfer phase). The final step is to identify the potential implementation (technological domain).This approach has been seen to be useful in creating new research opportunities based on biomimicry. In addition, suitable solutions arising from multidisciplinary team research are presented as promising answers to the challenges that building energy systems face nowadays. Keywords: Biomimicry, Building services, Energy systems, Passive design, Multidisciplinary

Soft exosuits stand out when it comes to the development of walking-assistance devices thanks to both their higher degree of wearability, lower weight, and price compared to the bulkier equivalent rigid exoskeletons. In cable-driven exosuits, the acting force is driven by cables from the actuation system to the anchor points; thus, the user’s movement is not restricted by a rigid structure. In this paper, a 3D inverse dynamics model is proposed and integrated with a model for a cable-driven actuation to predict the required motor torque and traction force in cables for a walking-assistance exosuit during gait. Joint torques are to be shared between the user and the exosuit for different design configurations, focusing on both hip and ankle assistance. The model is expected to guide the design of the exosuit regarding aspects such as the location of the anchor points, the cable system design, and the actuation units. An inverse dynamics analysis is performed using gait kinematic data from a public dataset to predict the cable forces and position of the exosuit during gait. The obtained joint reactions and cable forces are compared with those in the literature, and prove the model to be accurate and ready to be implemented in an exosuit control scheme. The results obtained in this study are similar to those found in the literature regarding the walking study itself as well as the forces under which cables operate during gait and the cable position cycle.

Atrial fibrillation (AF) alters left atrial (LA) hemodynamics, which can lead to thrombosis in the left atrial appendage (LAA), systemic embolism and stroke. A personalized risk-stratification of AF patients for stroke would permit improved balancing of preventive anticoagulation therapies against bleeding risk. We investigated how LA anatomy and function impact LA and LAA hemodynamics, and explored whether patient-specific analysis by computational fluid dynamics (CFD) can predict the risk of LAA thrombosis. We analyzed 4D-CT acquisitions of LA wall motion with an in-house immersed-boundary CFD solver. We considered six patients with diverse atrial function, three with either a LAA thrombus (removed digitally before running the simulations) or a history of transient ischemic attacks (LAAT/TIA-pos), and three without a LAA thrombus or TIA (LAAT/TIA-neg). We found that blood inside the left atrial appendage of LAAT/TIA-pos patients had marked alterations in residence time and kinetic energy when compared with LAAT/TIA-neg patients. In addition, we showed how the LA conduit, reservoir and booster functions distinctly affect LA and LAA hemodynamics. Finally, fixed-wall and moving-wall simulations produced different LA hemodynamics and residence time predictions for each patient. Consequently, fixed-wall simulations risk-stratified our small cohort for LAA thrombosis worse than moving-wall simulations, particularly patients with intermediate LAA residence time. Overall, these results suggest that both wall kinetics and LAA morphology contribute to LAA blood stasis and thrombosis.

La digitalización del profesorado universitario es un aspecto que ha cobrado especial relevancia en los últimos meses, de forma más concreta en el ámbito sanitario. Las clases presenciales se han visto canceladas y sustituidas por docencia online de una manera abrupta a causa de la crisis sanitaria acontecida. A ello se suma la elevada carga asistencial que han asumido todos los profesionales sanitarios. Varios de los hospitales del grupo Quirónsalud en Madrid desarrollan gran parte del plan académico del Grado de Medicina de la Universidad Europea y, debido a las circunstancias derivadas de la pandemia, su docencia ha tenido que transformarse, usando herramientas digitales que permitieran llevar a cabo tanto la labor docente como el arduo trabajo hospitalario de forma simultánea. Este artículo presenta los datos de la docencia llevada a cabo, así como las iniciativas que se han puesto en marcha desde marzo de 2020, con la finalidad de analizar la adaptación del claustro médico docente del grupo Quirónsalud a la situación acaecida. La utilización de herramientas asíncronas ha favorecido el trabajo autónomo del estudiante y la compatibilización de la actividad asistencial y la docencia en los hospitales mediante iniciativas como clases síncronas online, seminarios grabados y presentaciones locutadas, entre otras.

Background The determinants and consequences of pulmonary hypertension after successfully corrected valvular heart disease remain poorly understood. We aim to clarify the hemodynamic bases and risk factors for mortality in patients with this condition. Methods and Results We analyzed long‐term follow‐up data of 222 patients with pulmonary hypertension and valvular heart disease successfully corrected at least 1 year before enrollment who had undergone comprehensive hemodynamic and imaging characterization as per the SIOVAC (Sildenafil for Improving Outcomes After Valvular Correction) clinical trial. Median (interquartile range) mean pulmonary pressure was 37 mm Hg (32–44 mm Hg) and pulmonary artery wedge pressure was 23 mm Hg (18–26 mm Hg). Most patients were classified either as having combined precapillary and postcapillary or isolated postcapillary pulmonary hypertension. After a median follow‐up of 4.5 years, 91 deaths accounted for 4.21 higher‐than‐expected mortality in the age‐matched population. Risk factors for mortality were male sex, older age, diabetes mellitus, World Health Organization functional class III and higher pulmonary vascular resistance—either measured by catheterization or approximated from ultrasound data. Higher pulmonary vascular resistance was related to diabetes mellitus and smaller residual aortic and mitral valve areas. In turn, the latter correlated with prosthetic nominal size. Six‐month changes in the composite clinical score and in the 6‐minute walk test distance were related to survival. Conclusions Persistent valvular heart disease–pulmonary hypertension is an ominous disease that is almost universally associated with elevated pulmonary artery wedge pressure. Pulmonary vascular resistance is a major determinant of mortality in this condition and is related to diabetes mellitus and the residual effective area of the corrected valve. These findings have important implications for individualizing valve correction procedures. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00862043.

The present paper is focused on the application of a methodological model specifically designed to develop the tasks related to analysis and dissemination of the Roman Hispania site of Arucci (Aroche, Huelva). The main aim of our approach is to reconcile the diffusion of the results obtained after the excavation, documentation, and the study of the archaeological record with the methodological analysis of a Geographic Information System (GIS). We consider that a GIS is the most appropriate tool in archaeology for this purpose since it allows users to manage a large amount of data in diverse formats and insert it in a closed topographic reference frame. For that purpose, we restrict the field of action to the North House (a house built in the time of Emperor Augustus that lasted until the 3rd century AD). The real power of this research relies on the integration of the digital building archaeological record in a GIS, while the architecture of the Roman house is reconstructed virtually from archaeological remains, in this way the domestic space is visually comprehensible. According to the results obtained in this pilot experience, we can affirm that the union of GIS and infographics allows archaeological reality to surpass the strictly academic scope and promote it to society making possible the Arucci site approachable to professionals of archaeology as well as to the uninitiated. The feasibility of the proposal that was carried out within the North House encourages us to consider the export of this study model to the rest of buildings that make up the site such as the foro, macellum, balneum as, well as other domus.

Current clinical guidelines establish Pulmonary Vein (PV) isolation as the indicated treatment for Atrial Fibrillation (AF). However, AF can also be triggered or sustained due to atrial drivers located elsewhere in the atria. We designed a new simulation workflow based on personalized computer simulations to characterize AF complexity of patients undergoing PV ablation, validated with non-invasive electrocardiographic imaging and evaluated at one year after ablation. We included 30 patients using atrial anatomies segmented from MRI and simulated an automata model for the electrical modelling, consisting of three states (resting, excited and refractory). In total, 100 different scenarios were simulated per anatomy varying rotor number and location. The 3 states were calibrated with Koivumaki action potential, entropy maps were obtained from the electrograms and compared with ECGi for each patient to analyze PV isolation outcome. The completion of the workflow indicated that successful AF ablation occurred in patients with rotors mainly located at the PV antrum, while unsuccessful procedures presented greater number of driving sites outside the PV area. The number of rotors attached to the PV was significantly higher in patients with favorable long-term ablation outcome (1-year freedom from AF: 1.61 ± 0.21 vs. AF recurrence: 1.40 ± 0.20; p-value = 0.018). The presented workflow could improve patient stratification for PV ablation by screening the complexity of the atria.

The use of allogeneic adipose-derived mesenchymal stromal cells (alloADSCs) represents an attractive approach for treating myocardial infarction (MI). Furthermore, adding a natural support improves alloADSCs engraftment and survival in heart tissues, leading to a greater therapeutic effect. We aimed to examine the safety and immunological reaction induced by epicardial implantation of a clinical-grade collagen scaffold (CS) seeded with alloADSCs for its future application in humans. Thus, cellularized scaffolds were myocardially or subcutaneously implanted in immunosuppressed rodent models. The toxicological parameters were not significantly altered, and tumor formation was not found over the short or long term. Furthermore, biodistribution analyses in the infarcted immunocompetent rats displayed cell engraftment in the myocardium but no migration to other organs. The immunogenicity of alloADSC-CS was also evaluated in a preclinical porcine model of chronic MI; no significant humoral or cellular alloreactive responses were found. Moreover, CS cellularized with human ADSCs cocultured with human allogeneic immune cells produced no alloreactive response. Interestingly, alloADSC-CS significantly inhibited lymphocyte responses, confirming its immunomodulatory action. Thus, alloADSC-CS is likely safe and does not elicit any alloreactive immunological response in the host. Moreover, it exerts an immunomodulatory action, which supports its translation to a clinical setting.

La arquitectura doméstica de las ciudades occidentales del Conventus Hispalensis continúa siendo una línea de investigación abierta y aún por desarrollar. Así, a pesar de que existe una literatura arqueológica previa, hasta la fecha, no se había realizado un estudio que presentara una panorámica global que integrara el análisis de su arquitectura, programa ornamental, cultura material y su inserción en la trama urbana, factores explicativos de gran interés en la actualidad, a tenor del desarrollo que la arquitectura doméstica en Hispania ha sido objeto en las últimas décadas (Corrales, 2012, 256). Así, pues, se hacía necesaria la generación de un marco de trabajo teórico (Wallace– Hadrill, 1997, 219) mediante el cual, la edilicia doméstica de las ciudades del territorio onubense se entendiese como una reflexión global, en la que, de la mano de las nuevas evidencias arqueológicas, se pudiera producir una aproximación interpretativa renovada.

Background Blood pressure (BP) guidelines for patients with aortic stenosis or a history of aortic stenosis treated with aortic valve replacement (AVR) match those in the general population, but this extrapolation may not be warranted. Methods and Results Among patients enrolled in the Medtronic intermediate, high, and extreme risk trials, we included those with a transcatheter AVR (n=1794) or surgical AVR (n=1103) who were alive at 30 days. The associations between early (average of discharge and 30 day post‐AVR) systolic BP (SBP) and diastolic BP (DBP) measurements and clinical outcomes between 30 days and 1 year were evaluated. Among 2897 patients, after adjustment, spline curves demonstrated an association between lower SBP (

Hybrid orthoses or rehabilitation exoskeletons have proven to be a powerful tool for subjects with gait disabilities due to their combined use of electromechanical actuation to provide motion and support, and functional electrical stimulation (FES) to contract muscle tissue so as to improve the rehabilitation process. In these devices, each degree of freedom is governed by two actuators. The main issue arises in the design of the two actuation profiles for there to be natural or normative gait motion in which the two actuators are transparent to each other. Hybrid exoskeleton control solutions proposed in the literature have been based on tracking the desired kinematics and applying FES to maintain the desired motion rather than to attain the values expected for physiological movement. This work proposes a muscle-model approach involving inverse dynamics optimization for the design of combined actuation in hybrid orthoses. The FES profile calculated in this way has the neurophysiological meaningfulness for the device to be able to fulfill its rehabilitative purpose. A general scheme is proposed for a hybrid hip-knee-ankle-foot orthosis. The actuation profiles, when muscle tissue is fatigued due to FES actuation are analyzed, and an integrated approach is presented for estimating the actuation profiles so as to overcome muscle peak force reduction during stimulation. The objective is to provide a stimulation profile for each muscle individually that is compatible with the desired kinematics and actuation of the orthosis. The hope is that the results may contribute to the design of subject-specific rehabilitation routines with hybrid exoskeletons, improving the exoskeleton's actuation while maintaining its rehabilitative function.

Background: Intracardiac flow homeostasis requires avoiding blood stasis and platelet activation during its transit through the cardiac chambers. However, the foundations of intraventricular blood washout and its exposure to shear stresses have been poorly addressed. We aimed to characterize and quantify these features in a wide population of healthy subjects and assess the relationships of these indices with age.Methods: We used color-Doppler echocardiography and custom post-processing methods to study 149 healthy volunteers from 26 days to 80 years old. From the intraventricular flow-velocity fields we obtained personalized maps of (1) the residence time of blood in the LV, and (2) the shear index, a metric accounting for the strongest occurrence of shear stresses inside the chamber. From these maps we derived quantitative indices of the overall intraventricular blood washout and shear exposure. We addressed the age-dependence of these indices and analyzed their relationship with age-related changes in filling-flow.Results: The entire intraventricular blood pool was replaced before 8 cycles. Average residence time of blood inside the LV was

Vaccine hesitancy was one of the ten major threats to global health in 2019, according to the World Health Organisation. Nowadays, social media has an important role in the spread of information, misinformation, and disinformation about vaccines. Monitoring vaccine-related conversations on social media could help us to identify the factors that contribute to vaccine confidence in each historical period and geographical area. We used a hybrid approach to perform an opinion-mining analysis on 1,499,227 vaccine-related tweets published on Twitter from 1st June 2011 to 30th April 2019. Our algorithm classified 69.36% of the tweets as neutral, 21.78% as positive, and 8.86% as negative. The percentage of neutral tweets showed a decreasing tendency, while the proportion of positive and negative tweets increased over time. Peaks in positive tweets were observed every April. The proportion of positive tweets was significantly higher in the middle of the week and decreased during weekends. Negative tweets followed the opposite pattern. Among users with ≥2 tweets, 91.83% had a homogeneous polarised discourse. Positive tweets were more prevalent in Switzerland (71.43%). Negative tweets were most common in the Netherlands (15.53%), Canada (11.32%), Japan (10.74%), and the United States (10.49%). Opinion mining is potentially useful to monitor online vaccine-related concerns and adapt vaccine promotion strategies accordingly.

The design of the techniques and algorithms used by the static, dynamic and interactive security testing tools differ. Therefore, each tool detects to a greater or lesser extent each type of vulnerability for which they are designed for. In addition, their different designs mean that they have different percentages of false positives. In order to take advantage of the possible synergies that different analysis tools types may have, this paper combines several static, dynamic and interactive analysis security testing tools—static white box security analysis (SAST), dynamic black box security analysis (DAST) and interactive white box security analysis (IAST), respectively. The aim is to investigate how to improve the effectiveness of security vulnerability detection while reducing the number of false positives. Specifically, two static, two dynamic and two interactive security analysis tools will be combined to study their behavior using a specific benchmark for OWASP Top Ten security vulnerabilities and taking into account various scenarios of different criticality in terms of the applications analyzed. Finally, this study analyzes and discuss the values of the selected metrics applied to the results for each n-tools combination.

Perfusion decellularization of cadaveric hearts removes cells and generates a cell-free extracellular matrix scaffold containing acellular vascular conduits, which are theoretically sufficient to perfuse and support tissue-engineered heart constructs. This article contains additional data of our experience decellularizing and testing structural integrity and composition of a large series of human hearts, “Acellular human heart matrix: a critical step toward whole heat grafts” (Sanchez et al., 2015) [1]. Here we provide the information about the heart decellularization technique, the valve competence evaluation of the decellularized scaffolds, the integrity evaluation of epicardial and myocardial coronary circulation, the pressure volume measurements, the primers used to assess cardiac muscle gene expression and, the characteristics of donors, donor hearts, scaffolds and perfusion decellularization process.

Malware threats pose new challenges to analytic and reverse engineering tasks. It is needed for a systematic approach to that analysis, in an attempt to fully uncover their underlying attack vectors and techniques and find commonalities between them. In this paper, a method of malware analysis is described, together with a report of its application to the case of Flame and Red October. The method has also been used by different analysts to analyze other malware threats like ‘Stuxnet’, ‘Dark Comet’, ‘Poison Ivy’, ‘Locky’, ‘Careto’, and ‘Sofacy Carberp’. The method presented in this work is a systematic and methodological process of analysis, whose main objective is the acquisition of knowledge as well as to gain a full understanding of a particular malware. Using the proposed method to analyze two well-known malware as ‘Flame’ and ‘Red October’ will help to understand the added value of the method.

La Antropología de la Educación apareció, en nuestro país, en los planes formativos para las carreras universitarias del Magisterio a finales del siglo pasado y a pesar de su carácter, peso e interés, no ha permanecido vigente tras la última reconstrucción de planes realizada hace unos años. Este hecho no ha sucedido en otros países europeos como es el caso concreto de Alemania, cuna originaria del estudio antropológico-filosófico, donde, debido a su amplia tradición, goza de un gran prestigio tanto en los programas académicos como en la extensa bibliografía científica existente sobre la misma. Este artículo pretende ensalzar la importancia de la atención a la Antropología Pedagógica desde los planes de estudios en la formación de maestros partiendo de la tesis fundamental de que para la tarea educativa es necesario disponer de un foco antropológico sustancial que facilite la comprensión del ser humano y que fundamente la posibilidad del fenómeno educativo.

En este trabajo se realiza un análisis comparativo entre el que fue el principal puerto meridional de la Península Ibérica antes de la llegada de Roma -Gades- y el que asumirá esa condición predominante tras la conformación de la Provincia Baetica -Hispalis- gracias al impulso que le proporcionará su desarrollo como puerto annonario y puerta de entrada a la provincia tras las reformas augusteas. En la segunda mitad del s. I a.C. y especialmente a inicios del principado, ambas ciudades tendrán un importante crecimiento urbanístico, transformación y aumento de espacios productivos y crecimiento de sectores económicos. Sin embargo en el devenir del s. I d.C. el puerto hispalense tendrá un importante despegue como núcleo portuario bético, confirmado por indicadores económicos así como por la presencia de importantes magistrados y funcionarios imperiales.

El castellum de Tamuda, ubicado en las proximidades de la actual Tetuán (Marruecos), supone uno de los mejores ejemplos de arquitectura militar romana en las provincias mauritanas tanto por el grado de conservación como por los datos que hasta la fecha se tienen gracias a las campañas de excavación desarrolladas durante el periodo del protectorado español y las que actualmente se están llevando a cabo por parte de la Universidad de Huelva. Uno de los aspectos más novedosos a este respecto son los datos arqueoarquitectónicos que se desprenden del análisis paramental realizado en diversas partes de este campamento, de los cuales tendrán especial relevancia las torres SE y NO tradicionalmente adscritas como de abanico, planteamiento que a día de hoy debe ser modificado dado los nuevos datos con los que se cuentan.

La realidad del yacimiento de San Mamés (Aroche, Huelva) se encuentra a día de hoy ampliamente difundida en el mundo científico y académico, sin embargo las cuestiones referentes al proceso de implantación de Roma y el modelo que desarrolla, así como la problemática histórica que gira en torno a los topónimos Arucci Turobriga, ha visto una nueva interpretación gracias a las últimas investigaciones cuya explicación reside en una sola realidad topográfica y el trasfondo de un proceso jurídico por el que se establecerá la agregación administrativa del segundo con respecto al primero. Así, todo parece indicar que estaríamos ante el desarrollo de un proceso de implantación basado en un proceso de sinecismo, que verá en la mutatio oppidi del núcleo céltico de Arucci y la contribución de los núcleos célticos del territorio el surgimiento de una nueva fundación en los Llanos debido a los reajustes territoriales y administrativos desarrolladas en torno a las últimas décadas del siglo I a.C.

The north necropolis of city was an object of an important program of building towards the change of Age destined to show before the position reached by Onoba's city in the political - economic context of the Empire. In spite of it, the knowledge of this funeral area has seen strongly determined for the system of hills and water-course in which it placed, as well as for the nonexistence of an overall view derived from the multiple research's teams that they have worked on it.