Pindo: proyecto de investigación en la práctica docente

El cambio en el paradigma educativo de los últimos años trae consigo la organización de espacios supranacionales de educación y exige una revisión profunda de las metodologías docentes. Los diversos escenarios que han ido surgiendo con la revolución tecnológica nos permiten alcanzar un consenso en la forma de evaluar las competencias que los estudiantes han de adquirir en los diferentes niveles educativos. Para que este cambio sea efectivo es necesaria una organización de los equipos profesionales que excede el ámbito local (departamentos) y nacional (colaboración interuniversitaria en un país). Por este motivo, los profesores que participamos en este estudio, junto con varias instituciones de educación superior europeas y latinoamericanas, hemos desarrollado una propuesta acorde con las nuevas necesidades educativas en la universidad. Dicha propuesta, con su motivación, los objetivos que se consideran y la metodología para alcanzarlos, se detallan a lo largo de este artículo, con la finalidad de generar un debate que logre mejorarla e involucrar a más universidades para que aporten nuevos puntos de vista

Cryptographic properties of Boolean functions defining elementary cellular automata

In this work, the algebraic properties of the local transition functions of elementary cellular automata (ECA) were analysed. Specifically, a classification of such cellular automata was done according to their algebraic degree, the balancedness, the resiliency, nonlinearity, the propagation criterion and the existence of non-zero linear structures. It is shown that there is not any ECA satisfying all properties at the same time

An international code comparison study on coupled thermal, hydrologic and geomechanical processes of natural gas hydrate-bearing sediments

Highlights • Code comparisons build confidence in simulators to model interdependent processes. • International hydrate reservoir simulators are compared over five complex problems. • Geomechanical processes significantly impact response of gas hydrate reservoirs. • Simulators yielded comparable results, however many differences are noted. • Equivalent constitutive models are required to achieve agreement across simulators. Geologic reservoirs containing gas hydrate occur beneath permafrost environments and within marine continental slope sediments, representing a potentially vast natural gas source. Numerical simulators provide scientists and engineers with tools for understanding how production efficiency depends on the numerous, interdependent (coupled) processes associated with potential production strategies for these gas hydrate reservoirs. Confidence in the modeling and forecasting abilities of these gas hydrate reservoir simulators (GHRSs) grows with successful comparisons against laboratory and field test results, but such results are rare, particularly in natural settings. The hydrate community recognized another approach to building confidence in the GHRS: comparing simulation results between independently developed and executed computer codes on structured problems specifically tailored to the interdependent processes relevant for gas hydrate-bearing systems. The United States Department of Energy, National Energy Technology Laboratory, (DOE/NETL), sponsored the first international gas hydrate code comparison study, IGHCCS1, in the early 2000s. IGHCCS1 focused on coupled thermal and hydrologic processes associated with producing gas hydrates from geologic reservoirs via depressurization and thermal stimulation. Subsequently, GHRSs have advanced to model more complex production technologies and incorporate geomechanical processes into the existing framework of coupled thermal and hydrologic modeling. This paper contributes to the validation of these recent GHRS developments by providing results from a second GHRS code comparison study, IGHCCS2, also sponsored by DOE/NETL. IGHCCS2 includes participants from an international collection of universities, research institutes, industry, national laboratories, and national geologic surveys. Study participants developed a series of five benchmark problems principally involving gas hydrate processes with geomechanical components. The five problems range from simple geometries with analytical solutions to a representation of the world's first offshore production test of methane hydrates, which was conducted with the depressurization method off the coast of Japan. To identify strengths and limitations in the various GHRSs, study participants submitted solutions for the benchmark problems and discussed differing results via teleconferences. The GHRSs evolved over the course of IGHCCS2 as researchers modified their simulators to reflect new insights, lessons learned, and suggested performance enhancements. The five benchmark problems, final sample solutions, and lessons learned that are presented here document the study outcomes and serve as a reference guide for developing and testing gas hydrate reservoir simulators

Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19 : a multicentre, randomised, double-blind, non-inferiority phase IIb trial

A SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versus a homologous booster with BNT162b2 at 14, 28 and 98 days after vaccine administration. The HH-2 study is an ongoing multicentre, randomised, active-controlled, double-blind, non-inferiority Phase IIb trial, where participants 18 years or older who had received two doses of BNT162b2 were randomly assigned in a 2:1 ratio to receive a booster dose of vaccine-either heterologous (PHH-1V group) or homologous (BNT162b2 group)-in 10 centres in Spain. Eligible subjects were allocated to treatment stratified by age group (18-64 versus ≥65 years) with approximately 10% of the sample enrolled in the older age group. The primary endpoints were humoral immunogenicity measured by changes in levels of neutralizing antibodies (PBNA) against the ancestral Wuhan-Hu-1 strain after the PHH-1V or the BNT162b2 boost, and the safety and tolerability of PHH-1V as a boost. The secondary endpoints were to compare changes in levels of neutralizing antibodies against different variants of SARS-CoV-2 and the T-cell responses towards the SARS-CoV-2 spike glycoprotein peptides. The exploratory endpoint was to assess the number of subjects with SARS-CoV-2 infections ≥14 days after PHH-1V booster. This study is ongoing and is registered with , . From 15 November 2021, 782 adults were randomly assigned to PHH-1V (n = 522) or BNT162b2 (n = 260) boost vaccine groups. The geometric mean titre (GMT) ratio of neutralizing antibodies on days 14, 28 and 98, shown as BNT162b2 active control versus PHH-1V, was, respectively, 1.68 (p < 0.0001), 1.31 (p = 0.0007) and 0.86 (p = 0.40) for the ancestral Wuhan-Hu-1 strain; 0.62 (p < 0.0001), 0.65 (p < 0.0001) and 0.56 (p = 0.003) for the Beta variant; 1.01 (p = 0.92), 0.88 (p = 0.11) and 0.52 (p = 0.0003) for the Delta variant; and 0.59 (p ≤ 0.0001), 0.66 (p < 0.0001) and 0.57 (p = 0.0028) for the Omicron BA.1 variant. Additionally, PHH-1V as a booster dose induced a significant increase of CD4 + and CD8 + T-cells expressing IFN-γ on day 14. There were 458 participants who experienced at least one adverse event (89.3%) in the PHH-1V and 238 (94.4%) in the BNT162b2 group. The most frequent adverse events were injection site pain (79.7% and 89.3%), fatigue (27.5% and 42.1%) and headache (31.2 and 40.1%) for the PHH-1V and the BNT162b2 groups, respectively. A total of 52 COVID-19 cases occurred from day 14 post-vaccination (10.14%) for the PHH-1V group and 30 (11.90%) for the BNT162b2 group (p = 0.45), and none of the subjects developed severe COVID-19. Our interim results from the Phase IIb HH-2 trial show that PHH-1V as a heterologous booster vaccine, when compared to BNT162b2, although it does not reach a non-inferior neutralizing antibody response against the Wuhan-Hu-1 strain at days 14 and 28 after vaccination, it does so at day 98. PHH-1V as a heterologous booster elicits a superior neutralizing antibody response against the previous circulating Beta and the currently circulating Omicron BA.1 SARS-CoV-2 variants in all time points assessed, and for the Delta variant on day 98 as well. Moreover, the PHH-1V boost also induces a strong and balanced T-cell response. Concerning the safety profile, subjects in the PHH-1V group report significantly fewer adverse events than those in the BNT162b2 group, most of mild intensity, and both vaccine groups present comparable COVID-19 breakthrough cases, none of them severe. HIPRA SCIENTIFIC, S.L.U

Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods: We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings: Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. Interpretation: This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. Funding: Sanofi and Regeneron Pharmaceuticals

Numerical experiments on the convergence properties of state-based peridynamic laws and influence functions in two-dimensional problems

Peridynamics is widely used as the theoretical basis for numerical studies of fracture evolution, propagation, and behavior. While the theory has been shown to converge to continuum mechanics in the theoretical limit, its behavior as a discrete numerical approximation with respect to classic problems has not been shown. In this study, we use standard analytical solutions to thoroughly test the numerical accuracy and rate of convergence of the spatial discretization obtained by peridynamics. We analyze the accuracy and rate of convergence of three different peridynamic constitutive responses: of these, two involve a state-based dilation, and the third is based on the estimation of the deformation gradient. Additionally, we study the choice of the peridynamic influence function in each of the constitutive responses. The peridynamic materials are solved in the linear elastic regime by solving a linear system of equations obtained by symbolically differentiating the force states. We test the methods against standard constant-strain solutions for uniaxial compression, isotropic compression, and simple shear. We also apply the methods to a finite material with a pressurized thin crack, using the Westergaard's solution method to obtain an analytical displacement field for comparison. The two dilation-based peridynamic constitutive responses are found to only converge to one of the constant strain solutions, while the deformation gradient-based law converges in all cases with an appropriate choice of the influence functions. We show that a cubic influence function is the best choice of those considered in all methods. Only the deformation gradient-based model converges for all three linear deformation problems, but is less accurate than the dilation-based models for the thin crack problem because of instabilities. We demonstrate an ad hoc smoothing technique based on the influence function that is able to alleviate these instabilities and improve the accuracy of the deformation gradient-based model

Advanced malware propagation on random complex networks

[EN]In this work a novel model to simulate advanced malware spreading is introduced and analyzed. It is an individual-based model such that the dynamics of the malware outbreak is governed by means of a cellular automaton. The network topologies considered are complex random networks and each device is endowed at every step of time with one of the following possible states: susceptible, infected, attacked and recovered. A study analyzing the influence of topology variability and the structural characteristics of initially infected devices is done