Mathematical models in Developmental Biology

We will introduce some of the mathematical modeling tools that have been introduced in the field of Developmental Biology, focusing in specific problems in embryogenesis. The use of multiscale models based on a combination of ordinary and partial differential equations is a well established research paradigm in this area by now. After reviewing some of the past and present contributions, we will discuss both their merits and shortcomings in the light of recent experimental results.Universidad de Málaga. Campus de Excelencia Andalucía Tech

Anisotropic tempered diffusion equations

We introduce a functional framework which is specially suited to formulate several classes of anisotropic evolution equations of tempered diffusion type. Under an amenable set of hypothesis involving a very natural potential function, these models can be shown to belong to the entropy solution framework devised by [F. Andreu, V. Caselles, J. M. Mazo ́n, Nonlinear Anal. 61 (2005), J. Eur. Math. Soc. 7 (2005)], therefore ensuring well-posedness. We connect the properties of this potential with those of the associated cost function, thus providing a link with optimal transport theory and a supply of new examples of relativistic cost functions. Moreover, we characterize the anisotropic spreading properties of these models and we determine the Rankine–Hugoniot conditions that rule the temporal evolution of jump hypersurfaces under the given anisotropic flows.“Plan Propio de Investigación, programa 9” (funded by Universidad de Granada and european FEDER (ERDF) funds)Project RTI2018-098850-B-I00 (funded by MICINN and european FEDER funds)Project A-FQM-311-UGR18 (funded by Junta de Andalucía and european FEDER funds)Project P18-RT-2422 (funded by Junta de Andalucía and european FEDER funds

Desarrollo de herramientas y casos para el aprendizaje no presencial de Ingeniería de la Calidad

El nuevo paradigma de enseñanza-aprendizaje introducido por el Espacio Europeo de Educación Superior coloca al estudiante en el centro de su proceso de aprendizaje. En relación a ello, el sistema universitario español ha realizado en estos últimos años grandes esfuerzos de adaptación al nuevo planteamiento docente y a las nuevas metodologías utilizadas. Dentro de este contexto la enseñanza no presencial cobra cada vez mayor importancia, a ello debemos unir las herramientas informáticas con las que se cuenta a día de hoy para llevar a cabo una enseñanza de garantías. El objetivo del presente proyecto es la utilización de muchas de estas herramientas formativas que nos ofrecen las TIC´S (Tecnologías de la información y la comunicación) y los Entornos virtuales de aprendizaje para el desarrollo de un curso de formación no presencial de Ingeniería de la Calidad. Siendo el resultado final del mismo un ejemplo de curso en la plataforma web de enseñanza no presencial Moodle 2.3, en el que se han incluido ejemplos de contenidos teóricos, casos prácticos, vídeo-presentaciones explicativas, herramientas de comunicación profesor-estudiantes, etc. El desarrollo de este proyecto se encuentra enmarcado en una de las asignaturas del Máster Propio en Metrología Industrial e Ingeniería de la Calidad, estudio propio de la Universidad de Zaragoza. En la elaboración del mismo se ha procedido a la realización y resolución de diferentes casos prácticos ligados a determinados conceptos teóricos, aplicables a día de hoy al entorno industrial y a las diferentes necesidades demandadas por este. Los casos prácticos a desarrollar incluyen temas relacionados con metodologías de calidad de gran actualidad y peso en la industria actual: Lean Manufacturing, 6 sigma, Advanced Product Quality Planning (APQP), etc. Mediante el uso de Moodle 2.3 se ha optimizado la actividad docente no presencial, empleando para ello los recursos actuales de dicha herramienta, tales como: un espacio virtual para colgar el temario y los supuestos prácticos, foros, cuestionarios, etc. Además de la utilidad que nos ofrece Google Hangouts junto a YouTube para la aplicación de mensajería instantánea en la que gracias a su servicio de videoconferencias, permite realizar seminarios y tutorías online

Experiencias de Innovación docente en los Estudios Jurídicos: una visión práctica

Esta publicación se enmarca dentro de las actividades del Grupo de Investigación de la Universidad de Extremadura Fiscalitas & Iuris.Este trabajo surge con el objetivo principal de dar visibilidad y publicidad a las nuevas técnicas docentes en el seno de la Facultad de Derecho de la UEx. Como se sabe, se ha producido un innegable y significativo avance en el uso de nuevas técnicas docentes y también de las TICs aplicadas a la docencia en la Facultad de Derecho, no obstante, aún es necesario profundizar en el uso de las mismas y extenderlas entre todos los miembros del claustro de profesores, y fundamentalmente entre aquellos que llevan más años ejerciendo la docencia a través de la colaboración y la coordinación con los profesores noveles, que son quienes principalmente se sirven en mayor medida de tales instrumentos docentes. De otra parte, también era necesario que los docentes más experimentados pudieran encontrar un foro en el que transmitir y compartir con los noveles cuales son las técnicas e instrumentos docentes que ellos han venido utilizando durante el ejercicio de su magisterio, de modo que, en el marco de una relación sinalagmática, se produjera una interacción entre uno u otro grupo de docentes, a fin de fomentar el necesario debate y el intercambio de experiencias e instrumentos docentes, y en su caso el desarrollo y perfeccionamiento de los mismos; algo que hemos pretendido realizar con este trabajo, y que en buena medida hemos logrado. Las finalidades y objetivos concretos que perseguíamos, en atención a la situación expuesta eran fundamentalmente tres: • En primer lugar, la implementación de un proyecto de innovación docente integrado por una diversidad de actividades coordinadas, cada uno de ellas bajo la directa coordinación de un profesor o profesora de la UEx, aplicado a una o varias asignaturas impartidas en la Facultad de Derecho. • En segundo lugar, el establecimiento en la Facultad de Derecho de un foro de coordinación e intercambio de buenas prácticas docentes sobre la base de cada uno de las actividades coordinadas, en el que pudieran participar profesores noveles y veteranos. Para ello se desarrolló espacio virtual de innovación docente en estudios jurídicos, a través del Campus Virtual de la UEx, en el que los Profesores noveles y veteranos pudieron y puede compartir recursos e informaciones sobre prácticas de innovación. • Y, en tercer lugar, la difusión y consolidación de instrumentos de innovación docente directamente aplicadas a la docencia de los estudios jurídicos, mediante la transferencia de los resultados y la publicación de los mismos; a fin de que esta transferencia sirva de base a futuras profundizaciones en el campo de la innovación docente en los estudios jurídicos.Proyecto “Desarrollo, profundización e intercambio de buenas prácticas de innovación docente en la Facultad de Derecho” (UEx 2015-2016

The CARBA-MAP study: national mapping of carbapenemases in Spain (2014–2018)

Introduction:Infections caused by carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa, including isolates producing acquired carbapenemases, constitute a prevalent health problem worldwide. The primary objective of this study was to determine the distribution of the different carbapenemases among carbapenemase-producing Enterobacterales (CPE, specifically Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae complex, and Klebsiella aerogenes) and carbapenemase-producing P. aeruginosa (CPPA) in Spain from January 2014 to December 2018.Methods: A national, retrospective, cross-sectional multicenter study was performed. The study included the first isolate per patient and year obtained from clinical samples and obtained for diagnosis of infection in hospitalized patients. A structured questionnaire was completed by the participating centers using the REDCap platform, and results were analyzed using IBM SPSS Statistics 29.0.0.Results: A total of 2,704 carbapenemase-producing microorganisms were included, for which the type of carbapenemase was determined in 2692 cases: 2280 CPE (84.7%) and 412 CPPA (15.3%), most often using molecular methods and immunochromatographic assays. Globally, the most frequent types of carbapenemase in Enterobacterales and P. aeruginosa were OXA-48-like, alone or in combination with other enzymes (1,523 cases, 66.8%) and VIM (365 cases, 88.6%), respectively. Among Enterobacterales, carbapenemase-producing K. pneumoniae was reported in 1821 cases (79.9%), followed by E. cloacae complex in 334 cases (14.6%). In Enterobacterales, KPC is mainly present in the South and South-East regions of Spain and OXA-48-like in the rest of the country. Regarding P. aeruginosa, VIM is widely distributed all over the country. Globally, an increasing percentage of OXA-48-like enzymes was observed from 2014 to 2017. KPC enzymes were more frequent in 2017–2018 compared to 2014–2016.Discussion: Data from this study help to understand the situation and evolution of the main species of CPE and CPPA in Spain, with practical implications for control and optimal treatment of infections caused by these multi-drug resistant organisms

Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections

IMPORTANCE The consumption of broad-spectrum drugs has increased as a consequence of the spread of multidrug-resistant (MDR) Escherichia coli. Finding alternatives for these infections is critical, for which some neglected drugs may be an option. OBJECTIVE To determine whether fosfomycin is noninferior to ceftriaxone or meropenem in the targeted treatment of bacteremic urinary tract infections (bUTIs) due to MDR E coli. DESIGN, SETTING, AND PARTICIPANTS This multicenter, randomized, pragmatic, open clinical trial was conducted at 22 Spanish hospitals from June 2014 to December 2018. Eligible participants were adult patients with bacteremic urinary tract infections due to MDR E coli; 161 of 1578 screened patients were randomized and followed up for 60 days. Data were analyzed in May 2021. INTERVENTIONS Patients were randomized 1 to 1 to receive intravenous fosfomycin disodium at 4 g every 6 hours (70 participants) or a comparator (ceftriaxone or meropenem if resistant; 73 participants) with the option to switch to oral fosfomycin trometamol for the fosfomycin group or an active oral drug or pa renteral ertapenem for the comparator group after 4 days. MAIN OUTCOMES AND MEASURES The primary outcome was clinical and microbiological cure (CMC) 5 to 7 days after finalization of treatment; a noninferiority margin of 7% was considered. RESULTS Among 143 patients in the modified intention-to-treat population (median [IQR] age, 72 [62-81] years; 73 [51.0%] women), 48 of 70 patients (68.6%) treated with fosfomycin and 57 of 73 patients (78.1%) treated with comparators reached CMC (risk difference, -9.4 percentage points; 1-sided 95% CI, -21.5 to infinity percentage points; P = .10). While clinical or microbiological failure occurred among 10 patients (14.3%) treated with fosfomycin and 14 patients (19.7%) treated with comparators (risk difference, -5.4 percentage points; 1-sided 95% CI. -infinity to 4.9; percentage points; P = .19), an increased rate of adverse event-related discontinuations occurred with fosfomycin vs comparators (6 discontinuations [8.5%] vs 0 discontinuations; P = .006). In an exploratory analysis among a subset of 38 patients who underwent rectal colonization studies, patients treated with fosfomycin acquired a new ceftriaxone-resistant or meropenem-resistant gram-negative bacteria at a decreased rate compared with patients treated with comparators (0 of 21 patients vs 4 of 17 patients [23.5%]; 1-sided P = .01). CONCLUSIONS AND RELEVANCE This study found that fosfomycin did not demonstrate noninferiority to comparators as targeted treatment of bUTI from MDR E coli; this was due to an increased rate of adverse event-related discontinuations. This finding suggests that fosfomycin may be considered for selected patients with these infections

Somatic NLRP3 mosaicism in Muckle-Wells syndrome. A genetic mechanism shared by different phenotypes of cryopyrin-associated periodic syndromes

Familial cold autoinflammatory syndrome, Muckle-Wells syndrome (MWS), and chronic, infantile, neurological, cutaneous and articular (CINCA) syndrome are dominantly inherited autoinflammatory diseases associated to gain-of-function NLRP3 mutations and included in the cryopyrin-associated periodic syndromes (CAPS). A variable degree of somatic NLRP3 mosaicism has been detected in ≈35% of patients with CINCA. However, no data are currently available regarding the relevance of this mechanism in other CAPS phenotypes. OBJECTIVE: To evaluate somatic NLRP3 mosaicism as the disease-causing mechanism in patients with clinical CAPS phenotypes other than CINCA and NLRP3 mutation-negative. METHODS: NLRP3 analyses were performed by Sanger sequencing and by massively parallel sequencing. Apoptosis-associated Speck-like protein containing a CARD (ASC)-dependent nuclear factor kappa-light chain-enhancer of activated B cells (NF-κB) activation and transfection-induced THP-1 cell death assays determined the functional consequences of the detected variants. RESULTS: A variable degree (5.5-34.9%) of somatic NLRP3 mosaicism was detected in 12.5% of enrolled patients, all of them with a MWS phenotype. Six different missense variants, three novel (p.D303A, p.K355T and p.L411F), were identified. Bioinformatics and functional analyses confirmed that they were disease-causing, gain-of-function NLRP3 mutations. All patients treated with anti-interleukin1 drugs showed long-lasting positive responses. CONCLUSIONS: We herein show somatic NLRP3 mosaicism underlying MWS, probably representing a shared genetic mechanism in CAPS not restricted to CINCA syndrome. The data here described allowed definitive diagnoses of these patients, which had serious implications for gaining access to anti-interleukin 1 treatments under legal indication and for genetic counselling. The detection of somatic mosaicism is difficult when using conventional methods. Potential candidates should benefit from the use of modern genetic tool

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

CARB-ES-19 Multicenter Study of Carbapenemase-Producing Klebsiella pneumoniae and Escherichia coli From All Spanish Provinces Reveals Interregional Spread of High-Risk Clones Such as ST307/OXA-48 and ST512/KPC-3

ObjectivesCARB-ES-19 is a comprehensive, multicenter, nationwide study integrating whole-genome sequencing (WGS) in the surveillance of carbapenemase-producing K. pneumoniae (CP-Kpn) and E. coli (CP-Eco) to determine their incidence, geographical distribution, phylogeny, and resistance mechanisms in Spain.MethodsIn total, 71 hospitals, representing all 50 Spanish provinces, collected the first 10 isolates per hospital (February to May 2019); CPE isolates were first identified according to EUCAST (meropenem MIC &gt; 0.12 mg/L with immunochromatography, colorimetric tests, carbapenem inactivation, or carbapenem hydrolysis with MALDI-TOF). Prevalence and incidence were calculated according to population denominators. Antibiotic susceptibility testing was performed using the microdilution method (EUCAST). All 403 isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis.ResultsIn total, 377 (93.5%) CP-Kpn and 26 (6.5%) CP-Eco isolates were collected from 62 (87.3%) hospitals in 46 (92%) provinces. CP-Kpn was more prevalent in the blood (5.8%, 50/853) than in the urine (1.4%, 201/14,464). The cumulative incidence for both CP-Kpn and CP-Eco was 0.05 per 100 admitted patients. The main carbapenemase genes identified in CP-Kpn were blaOXA–48 (263/377), blaKPC–3 (62/377), blaVIM–1 (28/377), and blaNDM–1 (12/377). All isolates were susceptible to at least two antibiotics. Interregional dissemination of eight high-risk CP-Kpn clones was detected, mainly ST307/OXA-48 (16.4%), ST11/OXA-48 (16.4%), and ST512-ST258/KPC (13.8%). ST512/KPC and ST15/OXA-48 were the most frequent bacteremia-causative clones. The average number of acquired resistance genes was higher in CP-Kpn (7.9) than in CP-Eco (5.5).ConclusionThis study serves as a first step toward WGS integration in the surveillance of carbapenemase-producing Enterobacterales in Spain. We detected important epidemiological changes, including increased CP-Kpn and CP-Eco prevalence and incidence compared to previous studies, wide interregional dissemination, and increased dissemination of high-risk clones, such as ST307/OXA-48 and ST512/KPC-3

Dispersion vs diffusion in transport partial differential equations

Incluye Resumen y resultados escritos en inglés y españolTesis Univ. Granada. Departamento de Matemática Aplicada. Leída el 26 de marzo de 201