The effects of lithium sulfur battery ageing on second-life possibilities and environmental life cycle assessment studies

The development of Li-ion batteries has enabled the re-entry of electric vehicles into the market. As car manufacturers strive to reach higher practical specific energies (550 Wh/kg) than what is achievable for Li-ion batteries, new alternatives for battery chemistry are being considered. Li-Sulfur batteries are of interest due to their ability to achieve the desired practical specific energy. The research presented in this paper focuses on the development of the Li-Sulfur technology for use in electric vehicles. The paper presents the methodology and results for endurance tests conducted on in-house manufactured Li-S cells under various accelerated ageing conditions. The Li-S cells were found to reach 80% state of health after 300–500 cycles. The results of these tests were used as the basis for discussing the second life options for Li-S batteries, as well as environmental Life Cycle Assessment results of a 50 kWh Li-S batteryPeer ReviewedPostprint (published version

Electric vehicle battery health expected at end of life in the upcoming years based on UK data

Second-life businesses from Electric Vehicle (EV) batteries are gaining attention considering that these batteries are deemed as inappropriate for transport purposes once they reach 80 or 70% of State of Health (SoH). However, the limited number of retired batteries and the trend in battery capacity increase hinder a realistic evaluation of second-life applications. To analyze battery reuse, a closer look at the End of Life (EoL) conditions of these batteries must be taken. This study presents a battery ageing model to estimate the SoH of EV batteries according to their age and mileage. The model is applied to the current retirement characteristics of combustion vehicles to statistically determine the expected SoH at the vehicle EoL. Results indicate that most EVs will reach EoL for reasons other than under-performance. Once retired, most EV batteries will have a SoH higher than 75% within the next 20 years, opening an interesting market for second-life businesses. However, battery reuse is an option that, considering the growing EV market, will rapidly saturate the stationary energy storage demand. Before 2040, most EV batteries will follow streams towards the circular economy, although at some point, they will have to be sent directly to recycling after the vehicular use.Peer ReviewedObjectius de Desenvolupament Sostenible::11 - Ciutats i Comunitats Sostenibles::11.2 - Per a 2030, proporcionar accés a sistemes de transport segurs, assequibles, accessi­bles i sostenibles per a totes les persones, i millorar la seguretat viària, en particular mitjan­çant l’ampliació del transport públic, amb especial atenció a les necessitats de les persones en situació vulnerable, dones, nenes, nens, persones amb discapacitat i persones gransObjectius de Desenvolupament Sostenible::11 - Ciutats i Comunitats SosteniblesPostprint (published version

Procedure for Assessing the Suitability of Battery Second Life Applications after EV First Life

Using batteries after their first life in an Electric Vehicle (EV) represents an opportunity to reduce the environmental impact and increase the economic benefits before recycling the battery. Many different second life applications have been proposed, each with multiple criteria that have to be taken into consideration when deciding the most suitable course of action. In this article, a battery assessment procedure is proposed that consolidates and expands upon the approaches in the literature, and facilitates the decision-making process for a battery after it has reached the end of its first life. The procedure is composed of three stages, including an evaluation of the state of the battery, an evaluation of the technical viability and an economic evaluation. Options for battery configurations are explored (pack direct use, stack of battery packs, module direct use, pack refurbish with modules, pack refurbish with cells). By comparing these configurations with the technical requirements for second life applications, a reader can rapidly understand the tradeoffs and practical strategies for how best to implement second life batteries for their specific application. Lastly, an economic evaluation process is developed to determine the cost of implementing various second life battery configurations and the revenue for different end use applications. An example of the battery assessment procedure is included to demonstrate how it could be carried out.This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 963540 and No. 963580. This funding includes funds to support research work and open-access publications.Peer ReviewedPostprint (published version

First-Trimester Sequential Screening for Preeclampsia Using Angiogenic Factors: Study Protocol for a Prospective, Multicenter, Real Clinical Setting Study

IntroductionThe incidence of preeclampsia (PE) is about 2–8%, making it one of the leading causes of perinatal morbidity and maternal mortality in the world. Early prophylactic low dose administration (150 mg) of acetylsalicylic acid is associated with a significant reduction in the incidence of early-onset PE, intrauterine growth restriction (IUGR), and neonatal mean stay in the intensive care unit (ICU). Universal implementation of a first-trimester screening system including angiogenic and antiangiogenic markers [the Placental Growth Factor (PlGF) and/or soluble fms-like Tyrosine Kinase-1 (sFlt-1)] has shown a prediction rate of 90% for early-onset PE but entails a high financial cost. The aim of this study is to determine the predictive and preventive capacity of a universal PE first-trimester two-step sequential screening model, determining the PlGF only in patients previously classified as intermediate risk by means of a multivariate model based on resources already used in the standard pregnancy control, in a real clinical setting. We hypothesize that this screening model will achieve similar diagnostic performance as the universal determination of PlGF but at a lower economic cost.Methods and AnalysisThis is a prospective, multicentric, cohort study in a real-world clinical setting. Every singleton pregnancy will be recruited at the routine first pregnancy visit. In a first step, the first-trimester risk of PE will be calculated using a multivariate Gaussian distribution model, based on medical history, mean blood pressure, Pregnancy-Associated Plasma Protein A (PAPP-A), and Uterine Artery Doppler Pulsatility Index (UTPI). Patients will be classified into three risk groups for PE: (1) risk ≥ 1/50, high-risk with no further testing (blinded PlGF); (2) risk between 1/51 and 1/500, medium-risk requiring further testing; and (3) risk ≤ 1/501, low-risk with no further testing. In a second step, the PlGF will only be determined in those patients classified as intermediate risk after this first step, and then reclassified into high- or low-risk groups. Prophylactic administration of aspirin (150 mg/day) will be prescribed only in high risk patients. As a secondary objective, sFlt-1 values will be blindly determined in patients with high and intermediate risk to assess its potential performance in the screening for PE.Ethics and DisseminationThe study will be conducted in accordance with the principles of Good Clinical Practice. This study is approved by the Aragon Research Ethics Committee (CEICA) on 3 July 2020 (15/2020).Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT04767438

First-Trimester Sequential Screening for Preeclampsia Using Angiogenic Factors : Study Protocol for a Prospective, Multicenter, Real Clinical Setting Study

The incidence of preeclampsia (PE) is about 2-8%, making it one of the leading causes of perinatal morbidity and maternal mortality in the world. Early prophylactic low dose administration (150 mg) of acetylsalicylic acid is associated with a significant reduction in the incidence of early-onset PE, intrauterine growth restriction (IUGR), and neonatal mean stay in the intensive care unit (ICU). Universal implementation of a first-trimester screening system including angiogenic and antiangiogenic markers [the Placental Growth Factor (PlGF) and/or soluble fms-like Tyrosine Kinase-1 (sFlt-1)] has shown a prediction rate of 90% for early-onset PE but entails a high financial cost. The aim of this study is to determine the predictive and preventive capacity of a universal PE first-trimester two-step sequential screening model, determining the PlGF only in patients previously classified as intermediate risk by means of a multivariate model based on resources already used in the standard pregnancy control, in a real clinical setting. We hypothesize that this screening model will achieve similar diagnostic performance as the universal determination of PlGF but at a lower economic cost. This is a prospective, multicentric, cohort study in a real-world clinical setting. Every singleton pregnancy will be recruited at the routine first pregnancy visit. In a first step, the first-trimester risk of PE will be calculated using a multivariate Gaussian distribution model, based on medical history, mean blood pressure, Pregnancy-Associated Plasma Protein A (PAPP-A), and Uterine Artery Doppler Pulsatility Index (UTPI). Patients will be classified into three risk groups for PE: (1) risk ≥ 1/50, high-risk with no further testing (blinded PlGF); (2) risk between 1/51 and 1/500, medium-risk requiring further testing; and (3) risk ≤ 1/501, low-risk with no further testing. In a second step, the PlGF will only be determined in those patients classified as intermediate risk after this first step, and then reclassified into high- or low-risk groups. Prophylactic administration of aspirin (150 mg/day) will be prescribed only in high risk patients. As a secondary objective, sFlt-1 values will be blindly determined in patients with high and intermediate risk to assess its potential performance in the screening for PE. The study will be conducted in accordance with the principles of Good Clinical Practice. This study is approved by the Aragon Research Ethics Committee (CEICA) on 3 July 2020 (15/2020). , identifier: NCT04767438

Update in collecting duct carcinoma: Current aspects of the clinical and molecular characterization of an orphan disease

Bellini carcinoma; Clear-cell carcinoma; Collecting ductCarcinoma de Bellini; Carcinoma de cèl·lules clares; Conducte col·lectorCarcinoma de Bellini; Carcinoma de células claras; Conducto colectorCollecting duct renal cell carcinoma (cdRCC), which until recently was thought to arise from the collecting ducts of Bellini in the renal medulla, is a rare and aggressive type of non-clear renal cell carcinoma (ncRCC), accounting for 1% of all renal tumors and with nearly 50% of patients being diagnosed with Stage IV disease. The median overall survival in this setting is less than 12 months. Several regimens of chemotherapies had been used based on morphologic and cytogenetic similarities with urothelial cell carcinoma described previously, although the prognosis still remains poor. The use of targeted therapies also did not result in favorable outcomes. Recent works using NGS have highlighted genomic alterations in SETD2, CDKN2A, SMARCB1, and NF2. Moreover, transcriptomic studies have confirmed the differences between urothelial carcinoma and cdRCC, the possible true origin of this disease in the distal convoluted tubule (DCT), differentiating from other RCC (e.g., clear cell and papillary) that derive from the proximal convoluted tubule (PCT), and enrichment in immune cells that may harbor insights in novel treatment strategies with immunotherapy and target agents. In this review, we update the current aspects of the clinical, molecular characterization, and new targeted therapeutic options for Collecting duct carcinoma and highlight the future perspectives of treatment in this setting

Cardiac dysfunction and remodeling regulated by anti-angiogenic environment in patients with preeclampsia : the ANGIOCOR prospective cohort study protocol

Background: Cardiovascular diseases (CVD) are cause of increased morbidity and mortality in spite of advances for diagnosis and treatment. Changes during pregnancy affect importantly the maternal CV system. Pregnant women that develop preeclampsia (PE) have higher risk (up to 4 times) of clinical CVD in the short- and long-term. Predominance of an anti-angiogenic environment during pregnancy is known as main cause of PE, but its relationship with CV complications is still under research. We hypothesize that angiogenic factors are associated to maternal cardiac dysfunction/remodeling and that these may be detected by new cardiac biomarkers and maternal echocardiography. Methods: Prospective cohort study of pregnant women with high-risk of PE in first trimester screening, established diagnosis of PE during gestation, and healthy pregnant women (total intended sample size n = 440). Placental biochemical and biophysical cardiovascular markers will be assessed in the first and third trimesters of pregnancy, along with maternal echocardiographic parameters. Fetal cardiac function at third trimester of pregnancy will be also evaluated and correlated with maternal variables. Maternal cardiac function assessment will be determined 12 months after delivery, and correlation with CV and PE risk variables obtained during pregnancy will be evaluated. Discussion: The study will contribute to characterize the relationship between anti-angiogenic environment and maternal CV dysfunction/remodeling, during and after pregnancy, as well as its impact on future CVD risk in patients with PE. The ultimate goal is to improve CV health of women with high-risk or previous PE, and thus, reduce the burden of the disease. Trial registration: NCT04162236

A Genomic Approach for the Identification and Classification of Genes Involved in Cell Wall Formation and its Regulation in Saccharomyces Cerevisiae

Using a hierarchical approach, 620 non-essential single-gene yeast deletants generated by EUROFAN I were systematically screened for cell-wall-related phenotypes. By analyzing for altered sensitivity to the presence of Calcofluor white or SDS in the growth medium, altered sensitivity to sonication, or abnormal morphology, 145 (23%) mutants showing at least one cell wall-related phenotype were selected. These were screened further to identify genes potentially involved in either the biosynthesis, remodeling or coupling of cell wall macromolecules or genes involved in the overall regulation of cell wall construction and to eliminate those genes with a more general, pleiotropic effect. Ninety percent of the mutants selected from the primary tests showed additional cell wall-related phenotypes. When extrapolated to the entire yeast genome, these data indicate that over 1200 genes may directly or indirectly affect cell wall formation and its regulation. Twenty-one mutants with altered levels of β1,3-glucan synthase activity and five Calcofluor white-resistant mutants with altered levels of chitin synthase activities were found, indicating that the corresponding genes affect β1,3-glucan or chitin synthesis. By selecting for increased levels of specific cell wall components in the growth medium, we identified 13 genes that are possibly implicated in different steps of cell wall assembly. Furthermore, 14 mutants showed a constitutive activation of the cell wall integrity pathway, suggesting that they participate in the modulation of the pathway either directly acting as signaling components or by triggering the Slt2-dependent compensatory mechanism. In conclusion, our screening approach represents a comprehensive functional analysis on a genomic scale of gene products involved in various aspects of fungal cell wall formation

Biometría placentaria para predecir el riesgo de preeclampsia y alteraciones del crecimiento fetal

El cribratge de la preeclàmpsia (PE) precoç en el primer trimestre és possible en l’actualitat, el que permet aplicar tractaments preventius. S’ han avaluat diverses característiques ecogràfiques relatives a la mida i volum de la placenta en el primer trimestre, trobant una associació significativa amb el risc de desenvolupar PE o alteracions del creixement fetal. No obstant això, cap dels algoritmes de cribratge multivariables utilitzats actualment inclou variables placentàries de primer trimestre. L’ objectiu principal d’ aquesta tesi doctoral és analitzar el rendiment diagnòstic de la biometria placentària en el primer trimestre per al cribratge de la insuficiència placentària, de forma aïllada i combinada amb altres variables maternes, bioquímiques i biofísiques. Així mateix, s’ avaluaran els factors determinants de la mida placentària en primer trimestre, així com la relació entre la mida i volum placentaris, i les característiques maternes i obstètriques i el resultat perinatal. Les variables principals de resultat van ser el diagnòstic de PE o alteracions del creixement fetal (creixement intrauterí restringit o petit per a l’edat gestacional (PEG)). Les dades es van analitzar de forma individual per a cadascuna d’ aquestes variables, i de forma agrupada en forma de variables compostes de resultat segons criteri de severitat. Totes les variables es van ajustar per edat gestacional. Es va realitzar en primer lloc un estudi intra- i interobservador de les variables placentàries en estudi per comprovar la reproductibilitat de les mesures, i es van elaborar taules de referència de primer trimestre per a cadascuna d’ elles. A continuació, es va realitzar una anàlisi de correlació i una anàlisi bivariant per avaluar la relació entre la biometria placentària de primer i segon trimestre, i les característiques maternes, variables bioquímiques (proteïna plasmàtica A associada l’embaràs (PAPP-A) i placental growth factor), i variables biofísiques incloses en l’ estudi. Es van incloure 1340 en l’estudi. L’anàlisi intra- i interobservador va mostrar una bona reproductibilitat dels mesuraments placentaris en primer trimestre. Es va trobar una correlació positiva entre la biometria placentària i les variables bioquímiques estudiades, i una correlació negativa amb el Doppler de les artèries uterines. Hi va haver una correlació positiva entre la mida i volum placentaris en primer trimestre i el pes neonatal i placentari al néixer. En comparació amb les dones sense PE, les dones amb un resultat perinatal advers sever relacionat amb la insuficiència placentària van presentar un menor gruix i volum placentaris en primer trimestre. En canvi, no hi va haver diferències en comparació amb les dones amb PE a terme. Les dones amb fetus PEG van presentar una menor mida placentària per a totes les variables de biometria analitzades, tot i que les diferències respecte a a la placa basal i coriònica no van assolir la significació estadística. Entre els models de predicció analitzats per a les variables compostes de resultat perinatal advers, el que major rendiment diagnòstic va obtenir va incloure variables maternes, bioquímiques (PAPP-A), biofísiques i totes les variables de biometria placentària. La biometria placentària de primer trimestre, en el context d’ un cribratge multivariable, és d’ utilitat en la detecció precoç de gestacions amb risc de complicacions derivades de la insuficiència placentària, especialment per PEG. Els models de cribratge analitzats en aquest estudi van mostrar una bona capacitat de discriminació, però aquesta va ser inferior a la dels sistemes multivariables utilitzats en l’actualitat. Això suggereix que la incorporació de les variables placentàries en el cribratge de la PE i les seves complicacions és poc probable en el nostre medi.El cribado de la preeclampsia (PE) precoz en el primer trimestre es posible en la actualidad, lo que permite aplicar tratamientos preventivos. Se han evaluado diversas características ecográficas relativas al tamaño y volumen de la placenta en el primer trimestre, encontrando una asociación significativa con el riesgo de desarrollar PE o alteraciones del crecimiento fetal. No obstante, ninguno de los algoritmos de cribado multivariables utilizados actualmente incluye variables placentarias de primer trimestre. El objetivo principal de esta tesis doctoral es analizar el rendimiento diagnóstico de la biometría placentaria en el primer trimestre para el cribado de la insuficiencia placentaria, de forma aislada y combinada con otras variables maternas, bioquímicas y biofísicas. Asimismo, se evaluarán los factores determinantes del tamaño placentario en primer trimestre, así como la relación entre el tamaño y volumen placentarios, y las características maternas y obstétricas y el resultado perinatal. Las variables principales de resultado fueron el diagnóstico de PE o alteraciones del crecimiento fetal (crecimiento intrauterino restringido o pequeño para la edad gestacional (PEG)). Los datos se analizaron de forma individual para cada una de estas variables, y de forma agrupada en forma de variables compuestas de resultado según criterio de severidad. Todas las variables se ajustaron por edad gestacional. Se realizó en primer lugar un estudio intra- e interobservador de las variables placentarias en estudio para comprobar la reproductibilidad de las medidas, y se elaboraron tablas de referencia de primer trimestre para cada una de ellas. A continuación, se realizó un análisis de correlación y un análisis bivariante para evaluar la relación entre la biometría placentaria de primer y segundo trimestre, y las características maternas, variables bioquímicas (proteína plasmática A asociada el embarazo (PAPP-A) y placental growth factor), y variables biofísicas incluidas en el estudio. Se incluyeron 1340 en el estudio. El análisis intra- e interobservador mostró una buena reproductibilidad de las mediciones placentarias en primer trimestre. Se encontró una correlación positiva entre la biometría placentaria y las variables bioquímicas estudiadas, y una correlación negativa con el Doppler de las arterias uterinas. Hubo una correlación positiva entre el tamaño y volumen placentarios en primer trimestre y el peso neonatal y placentario al nacer. En comparación con las mujeres sin PE, las mujeres con un resultado perinatal adverso severo relacionado con la insuficiencia placentaria presentaron un menor grosor y volumen placentarios en primer trimestre. En cambio, no hubo diferencias en comparación con las mujeres con PE a término. Las mujeres con feto PEG presentaron un menor tamaño placentario para todas las variables de biometría analizadas, aunque las diferencias respecto a la placa basal y coriónica no alcanzaron la significación estadística. Entre los modelos de predicción analizados para las variables compuestas de resultado perinatal adverso, el que mayor rendimiento diagnóstico obtuvo incluyó variables maternas, bioquímicas (PAPP-A), biofísicas y todas las variables de biometría placentaria. La biometría placentaria de primer trimestre, en el contexto de un cribado multivariable, es de utilidad en la detección precoz de gestaciones con riesgo de complicaciones derivadas de la insuficiencia placentaria, especialmente para PEG. Los modelos de cribado analizados en este estudio mostraron una buena capacidad de discriminación, pero ésta fue inferior a la de los sistemas multivariables utilizados en la actualidad. Esto sugiere que la incorporación de las variables placentarias en el cribado de la PE y sus complicaciones es poco probable en nuestro medio.Early-onset preeclampsia (PE) screening in the first trimester is currently possible, allowing preventive treatments to be applied. Several ultrasound characteristics related to the size and volume of the placenta have been evaluated in the first trimester, finding a significant association with the risk of developing PE or foetal growth disorders. However, none of the multivariate screening algorithms currently used include first-trimester placental variables. The main objective of this project is to analyse the diagnostic performance of placental biometry in the first trimester for the screening of placental insufficiency, in isolation and combined with other maternal, biochemical and biophysical variables. Likewise, the determining factors of placental size in the first trimester will be evaluated, as well as the relationship between placental size and volume, and maternal and obstetric characteristics and perinatal outcome. The main outcome variables were the diagnosis of PE or foetal growth disorders (intrauterine growth restriction or small for gestational age (SGA)). Data were analyzed individually for each of these variables, and grouped as composite outcome variables according to severity criteria. All variables were adjusted by gestational age. First, an intra- and interobserver study of placental variables was carried out to assess the reproducibility of the measurements, and first trimester reference tables were prepared for each of them. Next, a correlation analysis and a bivariate analysis were performed to evaluate the relation between first and second trimester placental biometry, and maternal characteristics, biochemical variables (pregnancy associated plasma protein-A (PAPP-A) and placental growth factor), and biophysical variables included in the study. A total of 1340 women were included in the study. Intra- and interobserver analysis showed a good reproducibility of placental measurements in the first trimester. A positive correlation was found between placental biometry and the biochemical variables studied, and there was a negative correlation with uterine artery Doppler. There was also a positive correlation between placental size and volume in the first trimester and neonatal and placental weight at birth. Compared to women without PE, women with severe adverse perinatal outcomes related to placental insufficiency had lower first-trimester thickness and placental volume. However, there were no differences compared to women with term PE. Women with SGA foetuses had smaller placental measurements, although differences with respect to basal and corionnic plate did not reach statistical significance. Among the prediction models analyzed for the composite outcome variables, the highest diagnostic performance was obtained for the model including maternal, biochemical (PAPP-A), biophysical variables and all 2D and 3D ultrasound placental variables. First trimester placental biometry, in the context of a multivariate screening, is useful in the early detection of pregnancies at risk for placental insufficiency, especially for SGA. The screening models analyzed in this study showed a good capacity for discrimination, but this was lower than that of the multivariate systems currently used in clinical practice. This suggests that the incorporation of placental variables in PE screening and its complications is unlikely in our environment.Universitat Autònoma de Barcelona. Programa de Doctorat en Pediatria, Obstetrícia i Ginecologi