Estudio de aplicabilidad de humedales artificiales para la mejora de la calidad de las aguas en los meandros abandonados del río Segura

[ES] La actuación consiste en la utilización de tres meandros abandonados del río Segura, actualmente incluidos en el catálogo de zonas húmedas de la Comunidad Valenciana para la instalación de unos humedales artificiales que permitan depurar y mejorar la calidad del agua del río Segura mediante fitodepuración.[CA] L'actuació consistix en la utilització de tres meandres abandonats del riu Segura, actualment inclosos en el catàleg de zones humides de la Comunitat Valenciana per a la instal·lació d'uns aiguamolls artificials que permeten depurar i millorar la qualitat de l'aigua del riu Segura per mitjà de fitodepuració.[EN] The action consists in the use of three meanders abandoned the river Segura, currently included in the list of wetlands of the Community of Valencia for the installation of constructed wetlands that enable debug and improve the water quality of the River Segura through Phytodepuration.Soto Fuster, JL. (2016). Estudio de aplicabilidad de humedales artificiales para la mejora de la calidad de las aguas en los meandros abandonados del río Segura. http://hdl.handle.net/10251/70818.Archivo delegad

Diseño de un nuevo trazado de carretera C-90

[ES] Realizar todo el proceso de diseño Geométrico de una nueva carretera, con estudio de alternativas y justificación y desarrollo de alternativa elegida. Todo ello con el software profesional de Diseño de carreteras. Cumpliendo la normativa vigente.[EN] Carry out the entire Geometric design process of a new road, with study of alternatives and justification and development of the chosen alternative. All this with professional road design software. Complying with current regulations.Martí Fuster, JL. (2021). Diseño de un nuevo trazado de carretera C-90. Universitat Politècnica de València. http://hdl.handle.net/10251/173995TFG

Recaída de la leucemia aguda linfoblástica en la infancia: resultados actuales del tratamiento y nuevas alternativas terapéuticas

Introducción. La leucemia aguda linfoblástica (LAL) es la enfermedad maligna más frecuente en la infancia. A pesar de los avances logrados en el tratamiento de primera línea, la recaída sigue siendo el principal obstáculo para la curación con resultados de supervivencia global (SG) inferiores al 50% con los abordajes clásicos que incluyen la quimioterapia, la radioterapia y el trasplante hematopoyético alogénico (TPH) de donante compatible, por lo que la LAL sigue siendo una de las causas principales de muerte por cáncer en niños. La incidencia de la recaída es escasa y para generar conocimiento es preciso el trabajo colaborativo desarrollando esquemas diagnósticos y terapéuticos y registros que permitan su abordaje de forma unificada y el análisis de los resultados. La guía de recomendaciones terapéuticas “LAL/SEHOP-PETHEMA 2015” se elaboró con esta intención por iniciativa del grupo de trabajo de leucemia de la Sociedad Española de Hematología y Oncología Pediátricas (SEHOP). Es necesaria la incorporación de nuevos fármacos y estrategias de tratamiento para mejorar los resultados y para intentar reducir la incidencia de secuelas tardías o permanentes y es precisa la colaboración estrecha entre los clínicos con experiencia en recaída y los investigadores pre-clínicos. Nuevas estrategias de inmunoterapia basadas en el empleo de anticuerpos monoclonales (AMs) y células T dotadas de receptores antigénicos quiméricos (CARTs) se han incorporado recientemente al arsenal terapéutico frente a esta enfermedad. Objetivos. 1) Evaluar la experiencia clínica en España con los AMs blinatumomab e inotuzumab ozogamicina (InO) en niños con LAL. 2) Describir una experiencia pre-clínica orientada a identificar nuevas dianas terapéuticas para la aplicación de estrategias de tratamiento con linfocitos T modificados (CARTs). 3) Revisar los resultados recientes del tratamiento convencional de la primera recaída de la LAL en niños en España. 4) Evaluar el papel del TPH de donante haploidéntico como alternativa al TPH de donante HLA compatible como tratamiento de consolidación en los pacientes pediátricos con LAL en segunda remisión completa (RC2). Metodología. 1) Estudio retrospectivo y análisis de la tasa de respuesta, la toxicidad y los resultados de supervivencia tras el tratamiento con blinatumomab e InO en una serie de 29 pacientes pediátricos con LAL procedentes de 11 instituciones españolas. 2) Generación de un anticuerpos anti-CD22, desarrollo de un CART dirigido a una secuencia distal del antígeno CD22 y evaluación de su eficacia in vitro e in vivo. 3) Análisis de los resultados de SG y supervivencia libre de evento (SLE) de una cohorte de 76 pacientes pediátricos incluidos en el registro de la guía “LAL/SEHOP-PETHEMA 2015” y revisión de la experiencia publicada con blinatumomab en niños tras la primera recaída. 4) Comparación de los resultados del TPH a partir de donante haploidéntico (n = 25) o donante compatible (n = 51) en niños con LAL en RC2. Conclusiones. 1) Blinatumomab e InO fueron eficaces para inducir la remisión completa en un 47,6% de pacientes con LAL en situación avanzada. 2) Describimos un nuevo CART con elevada afinidad por un epítopo distal de CD22 que es capaz de eliminar eficientemente muestras de LAL in vitro e in vivo. 3) Tras una mediana de seguimiento de 12,5 meses, con el tratamiento estándar de la primera recaída de LAL, obtuvimos tasas de SLE y SG a 3 años de 40,1 ± 12,5% y 54,8 ± 14.9% (59,3 ± 16,8% y 71,2 ± 15, 2% para riesgo estándar; 13,5 ± 14,8% y 33,3 ± 23,9% para alto riesgo). A juzgar por los resultados obtenidos en dos ensayos clínicos prospectivos aleatorizados, los autores reclaman que se facilite el acceso al tratamiento con blinatumomab en todos los niños con primera recaída de alto riesgo de LAL. 4) Los resultados de supervivencia del TPH a partir de donante haploidéntico no difieren de los obtenidos con el TPH de donante compatible; la enfermedad de injerto con receptor crónica tiene un impacto favorable y la enfermedad residual mínima ≥ 0,01% antes del TPH un impacto desfavorable en la supervivencia libre de leucemia.Introduction. Acute lymphoblastic leukemia (ALL) is the most common malignant disease in childhood. Even though results from first line treatment have dramatically improved during recent decades, relapse remains the main cause of treatment failure with overall survival (OS) below 50% after first relapse in patient undergoing standard treatment approaches, including chemotherapy, radiotherapy and allogeneic stem cell transplantation (SCT) from an HLA compatible donor. As a consequence, ALL remains one of the major causes of cancer-related death among children. Incidence of relapse is low and, in order to gain knowledge and improve treatment results, collaborative efforts are needed in order to elaborate coordinated diagnostic and therapeutic approaches and to collect data allowing the analysis of results. With this aim, the “LAL/SEHOP-PETHEMA 2015” recommendation guidelines were developed by the leukemia working group of the Spanish Society of Pediatric Hematology and Oncology (SEHOP). In order to improve current results and reduce the incidence of long-term adverse events it will be necessary to incorporate novel drugs and treatment approaches, and close collaboration among experts in ALL relapse and basic researchers is crucial. New immunotherapy-based treatment modalities such as monoclonal antibodies (MAs) and chimeric antigen receptor T-cell (CART) therapy have recently been incorporated as treatment options for ALL. Objectives. 1) To evaluate early clinical experience in Spain with the MAs blinatumomab and inotuzumab oaogamycin (InO) in children with ALL. 2) To describe a pre-clinical experience directed to identify novel targets for the applications of new modified T-cell strategies (CART). 3) To analyze recent treatment outcomes after standard treatment of children with first relapse of ALL in Spain. 4) To evaluate the role of haploidentical donor as an alternative to HLA-compatible SCT as consolidation of children with second complete remission (CR2) of ALL. Methods. 1) Retrospective analysis of treatment results (rate of response, toxicity and outcome) from 29 children from 11 Spanish institution undergoing treatment with blinatumomab and InO. 2) Development of an anti-CD22 antibody and a membrane-distal epitope of the CD22 antigen targeted CART and evaluation of its efficacy in vitro and in vivo. 3) Analysis of OS and event free survival (EFS) rates from 76 children with first relapse of ALL undergoing standard treatment according to the “LAL/SEHOP-PETHEMA 2015” guidelines. 4) Comparative analysis of outcome in children with ALL undegoing SCT in CR2 from haploidental (n = 25) versus HLA-compatible donors (n = 51). Conclusions. 1) Blinatumomab and InO were able to induce complete remissions in 47.6% of heavily pre-treated advanced stage ALL patients. 2). Our novel CART hCD22.7, with high affinity for a membrane-distal epitope of CD22, efficiently eliminate ALL samples in vitro and in vivo. 3) After a median follow up of 12.5 months, with standard treatment for ALL first relapse, we found 3-year EFS and OS rates of 40.1 ± 12.5% and 54.8 ± 14.9%, respectively (59.3±16.8% and 71.2±15.2% for standard risk; 13.5 ± 14.8% and 33.3 ± 23.9% for high risk patients). According to recent data reported from two prospective randomized studies, the authors claim to provide accessibility to blinatumomab for all children after high risk first relapse of ALL in Spain. 4) We found no differences in treatment outcome among patients undergoing haploidentical versus HLA-compatible donor SCT. Chronic graft versus host disease had protective impact, and minimal residual disease ≥ 0.01% before SCT had unfavorable impact on leukemia free survival

Alternativas de recogida, tratamiento y eliminación de residuos sólidos urbanos

[EN] It is a monograph that analyzes the systems for the collection of existing waste, the different types of treatment and recovery, and the final disposal of the waste.[ES] Es un trabajo monográfico que analiza los sistemas de recogida de residuos existente, los diferentes tipos de tratamiento y valorización y la eliminación final de los residuos.[CA] És un treball monogràfic que analitza els sistemes d'arreplega de residus existent, els diferents tipus de tractament i valoració i l'eliminació final dels residus.Soto Fuster, JL. (2014). Alternativas de recogida, tratamiento y eliminación de residuos sólidos urbanos. http://hdl.handle.net/10251/39869.Archivo delegad

Numerical iterative methods for Markovian dependability and performability models: new results and a comparison

In this paper we deal with iterative numerical methods to solve linear systems arising in continuous-time Markov chain (CTMC) models. We develop an algorithm to dynamically tune the relaxation parameter of the successive over-relaxation method. We give a sufficient condition for the Gauss-Seidel method to converge when computing the steady-state probability vector of a finite irreducible CTMC, an a suffient condition for the Generalized Minimal Residual projection method not to converge to the trivial solution 0 when computing that vector. Finally, we compare several splitting-based iterative methods an a variant of the Generalized Minimal Residual projection method.Postprint (published version

Recreational Drug Use in People Living with HIV in Spain : Factors Associated with Drug Use and the Impact on Clinical Outcomes

We analysed the impact of recreational drug use (RDU) on different outcomes in people living with HIV (PLHIV). A multicentre retrospective cohort study was performed with two cohorts of PLHIV included: people using recreational drugs (PURD) vs. people not using recreational drugs (PNURD). Overall, 275 PLHIV were included. RDU was associated with men having sex with men (OR 4.14, 95% CI [1.14, 5.19]), previous sexually transmitted infections (OR 4.00, 95% CI [1.97, 8.13]), and current smoking (OR 2.74, 95% CI [1.44, 5.19]). While the CD/CD ratio increased amongst PNURD during the follow-up year, it decreased amongst PURD (p = 0.050). PURD presented lower scores of self-reported and multi-interval antiretroviral adherence (p = 0.017, and p = 0.006, respectively), emotional well-being (p < 0.0001), and regular follow-up (p = 0.059), but paid more visits to the emergency unit (p = 0.046). RDU worsens clinical, immunological, and mental health outcomes amongst PLHIV

An analysis of safety evidence management with the Structured Assurance Case Metamodel

SACM (Structured Assurance Case Metamodel) it a standard for assurance case specification and exchange. It consists of an argumentation metamodel and an evidence metamodel for justifying that a system satisfies certain requirements. For assurance of safety-critical systems, SACM can be used to manage safety evidence and to specify safety cases. The standard is a promising initiative towards harmonizing and improving system assurance practices, but its suitability for safety evidence management needs to be further studied. To this end, this paper studies how SACM 1.1 supports this activity according to requirements from industry and from prior work. We have analysed the notion of evidence in SACM, its evidence lifecycle, the classes and associations of the evidence metamodel, and the link of this metamodel with the argumentation one. As a result, we have identified several improvement opportunities and extension possibilities in SACM

Inception 1D-convolutional neural network for accurate prediction of electrical insulator leakage current from environmental data during its normal operation using long-term recording

[EN] Contamination flashover remains one of the biggest challenges for power grid designers and maintenance engineers. Insulator leakage current contains relevant information about their state so that continuous monitoring is considered the most effective way to prevent contamination flashover. In this work, we attempted to accurately predict insulator leakage current in real time during normal operations based on environmental data using long-term recordings. We first confirmed that the history of environmental data also contained relevant information to predict leakage current by conditional Granger analysis and determined that 20 was the optimal previous samples number for this purpose. We then compared the performance of typical regression models and convolutional neural network (CNN), when using both current and the last 21 samples as input features. We confirmed that the model with the last 21 samples might perform significantly better. Input features pre-processing by cascaded inception architecture was fundamental to capture the complex dynamic interaction between environmental data and leakage current and significantly improved the model performance. CNN based on inception architecture performed much better, achieving an average R2 of 0.94 ±0.03. The proposed model could be used to predict leakage current in both porcelain insulators with or without coatings and silicone composite insulators. Our results pave the way for creating an on-line pre-warning system adapted to individual installations, can anticipate the negative consequences of weather and/or pollution deposits and is useful for designing a strategic high-voltage electrical insulator preventive maintenance plan for preventing contamination flashover and thus increase power grid reliability and resilience.This work was supported by the Spanish Ministry of Economy and Competitiveness, Spain, the European Regional Development Fund (MCIU/AEI/FEDER, UE RTI2018-094449-A-I00-AR) .Bueno Barrachina, JM.; Ye Lin, Y.; Nieto Del-Amor, F.; Fuster Roig, VL. (2023). Inception 1D-convolutional neural network for accurate prediction of electrical insulator leakage current from environmental data during its normal operation using long-term recording. Engineering Applications of Artificial Intelligence. 119. https://doi.org/10.1016/j.engappai.2022.10579911

Novel technique for estimating pollution-associated leakage current in high voltage insulators based on adaptive filtering in long-term recording

[EN] Moist polluting substances on high-voltage insulator surfaces can cause power-line failures by triggering electric arcs. There are at present no effective methods of measuring insulator pollution levels during normal operations. In this work, we attempt to estimate insulator pollution leakage current (PLC) as an indirect method of measuring deposits in a 30 month period of simultaneously recording leakage current and related environmental variables in substation insulators. We analyzed the relationship between raw leakage current and environmental variables. We canceled out the influence of relative humidity on leakage current by adaptive filtering and then obtained the PLC by filtering out the anomalous peaks in the recording. The proposed method considerably reduces the correlation between leakage current and relative humidity (0.826 vs 0.019). The resulting signal was only slightly correlated with other environmental variables (<0.03), suggesting that the relationships between leakage current and temperature, wind direction and speed are mainly attributable to their influence on relative humidity. The PLC presents a quasi-annual smooth fluctuation over time with a magnitude similar to those obtained in laboratory tests. This novel technique could be used to monitor insulator PLC in real time and thus improve power supply continuity and reduce maintenance costs.Bueno-Barrachina, J.; Cañas Peñuelas, CS.; Ye Lin, Y.; Fuster Roig, VL. (2021). Novel technique for estimating pollution-associated leakage current in high voltage insulators based on adaptive filtering in long-term recording. Measurement Science and Technology. 32(5):1-10. https://doi.org/10.1088/1361-6501/abea3dS11032

The CNIC-Polypill reduces recurrent major cardiovascular events in real-life secondary prevention patients in Spain: The NEPTUNO study.

To evaluate the effectiveness of a cardiovascular polypill including aspirin, ramipril and atorvastatin (CNIC-Polypill), on the incidence of recurrent major cardiovascular events (MACE) and risk factor control in patients with established atherosclerotic cardiovascular disease (ASCVD) vs different pharmacological therapeutic strategies. Retrospective, observational study using data from electronic-health records. Patients were distributed into 4 different cohorts: CNIC-Polypill (case cohort) vs 3 control cohorts: same monocomponents taken separately (Monocomponents), equipotent drugs (Equipotent) and other drugs not included in the previous cohorts (Other therapies). Patients were followed for 2 years or until MACE or death. After propensity score matching, a total of 6456 patients (1614 patients per cohort) were analysed. After 2 years, the risk of recurrent MACE was lower in the CNIC-Polypill cohort compared to the control groups (22%; p = 0.017, 25%; p = 0.002, 27%; p = 0.001, higher in the Monocomponents, Equipotent and Other therapies cohorts, respectively). The incremental proportion of patients who achieved blood pressure (BP) and low-density lipoprotein cholesterol (LDLc) control from baseline was higher in the CNIC-Polypill cohort vs control cohorts (BP controlled patients: +12.5% vs + 6.3%; p < 0.05, +2.2%; p < 0.01, +2.4%; p < 0.01, LDLc controlled patients: +10.3% vs + 4.9%; p < 0.001, +5.7%; p < 0.001, +4.9%; p < 0.001, respectively). Medication persistence was higher in patients treated with the CNIC-Polypill (72.1% vs 62.2%, 60.0% and 54.2%, respectively; p < 0.001) at study end. In secondary prevention patients, compared with control groups, treatment with the CNIC-Polypill was associated with significant reductions in the accumulated incidence of recurrent MACE, improved BP and LDLc control rates, and increased medication persistence.FerrerS