Life cycle assessment of alternative processes to treat fly ash from waste incineration

Unsustainable consumption and production patterns, together with industrialization and population growth, have increased the generation of municipal solid waste (MSW), causing several environmental problems. The European Waste Framework Directive (WFD) sets waste prevention, preparation for reuse and recycling as priority strategies. Nevertheless, still a great amount of MSW ends up in landfills and waste-to-energy (WtE) plants. WtE plants reduces waste volume and allows efficient recovery of energy, however, incineration results in various types of solid wastes, bottom, boiler and fly ashes (FA). Due to the concentration of dangerous substances, FA are treated by means of stabilisation/solidification (S/S), thermal treatments or combined treatments, to reduce their toxicity and to avoid negative impacts on the environment and human health. Among S/S alternatives, stabilisation with cement and carbonation are one of the most popular. To determine the environmental performance of these processes this paper conducted a life cycle assessment (LCA). The study evaluated FA stabilisation with cement and water and FA carbonation for 55 % and 100 % excess of CO2 in the flue gas at the outlet of the reactor, and pressures of 1, 5, 10, 15 and 20 bar. The results showed that the range of pressure between 3 and 4 bar, and 55 % excess of CO2 in the flue gas have an efficient performance. The comparison of FA carbonation and stabilization displayed that the latter has higher impacts than the alternative carbonation due mainly to the cement production and the reduction of lixiviation and CO2 capture in the ash

Heterogeneous Infectivity and Pathogenesis of SARS-CoV-2 Variants Beta, Delta and Omicron in Transgenic K18-hACE2 and Wildtype Mice

The emerging SARS-CoV-2 variants of concern (VOCs) may display enhanced transmissibility, more severity and/or immune evasion; however, the pathogenesis of these new VOCs in experimental SARS-CoV-2 models or the potential infection of other animal species is not completely understood. Here we infected K18-hACE2 transgenic mice with B.1, B.1.351/Beta, B.1.617.2/Delta and BA.1.1/Omicron isolates and demonstrated heterogeneous infectivity and pathogenesis. B.1.351/Beta variant was the most pathogenic, while BA.1.1/Omicron led to lower viral RNA in the absence of major visible clinical signs. In parallel, we infected wildtype (WT) mice and confirmed that, contrary to B.1 and B.1.617.2/Delta, B.1.351/Beta and BA.1.1/Omicron can infect them. Infection in WT mice coursed without major clinical signs and viral RNA was transient and undetectable in the lungs by day 7 post-infection. In silico modeling supported these findings by predicting B.1.351/Beta receptor binding domain (RBD) mutations result in an increased affinity for both human and murine ACE2 receptors, while BA.1/Omicron RBD mutations only show increased affinity for murine ACE2.info:eu-repo/semantics/publishedVersio

Heterogeneous Infectivity and Pathogenesis of SARS-CoV-2 Variants Beta, Delta and Omicron in Transgenic K18-hACE2 and Wildtype Mice

Altres ajuts: Fundació La Marató de TV3 202126-30-21The emerging SARS-CoV-2 variants of concern (VOCs) may display enhanced transmissibility, more severity and/or immune evasion; however, the pathogenesis of these new VOCs in experimental SARS-CoV-2 models or the potential infection of other animal species is not completely understood. Here we infected K18-hACE2 transgenic mice with B.1, B.1.351/Beta, B.1.617.2/Delta and BA.1.1/Omicron isolates and demonstrated heterogeneous infectivity and pathogenesis. B.1.351/Beta variant was the most pathogenic, while BA.1.1/Omicron led to lower viral RNA in the absence of major visible clinical signs. In parallel, we infected wildtype (WT) mice and confirmed that, contrary to B.1 and B.1.617.2/Delta, B.1.351/Beta and BA.1.1/Omicron can infect them. Infection in WT mice coursed without major clinical signs and viral RNA was transient and undetectable in the lungs by day 7 post-infection. In silico modeling supported these findings by predicting B.1.351/Beta receptor binding domain (RBD) mutations result in an increased affinity for both human and murine ACE2 receptors, while BA.1/Omicron RBD mutations only show increased affinity for murine ACE2

Role of the first WHO mutation catalogue in the diagnosis of antibiotic resistance in Mycobacterium tuberculosis in the Valencia Region, Spain: a retrospective genomic analysis

9 páginas, 2 figuras, 1 tablaBackground: In June, 2021, WHO published the most complete catalogue to date of resistance-conferring mutations in Mycobacterium tuberculosis. Here, we aimed to assess the performance of genome-based antimicrobial resistance prediction using the catalogue and its potential for improving diagnostics in a real low-burden setting. Methods: In this retrospective population-based genomic study M tuberculosis isolates were collected from 25 clinical laboratories in the low-burden setting of the Valencia Region, Spain. Culture-positive tuberculosis cases reported by regional public health authorities between Jan 1, 2014, and Dec 31, 2016, were included. The drug resistance profiles of these isolates were predicted by the genomic identification, via whole-genome sequencing (WGS), of the high-confidence resistance-causing variants included in the catalogue and compared with the phenotype. We determined the minimum inhibitory concentration (MIC) of the isolates with discordant resistance profiles using the resazurin microtitre assay. Findings: WGS was performed on 785 M tuberculosis complex culture-positive isolates, and the WGS resistance prediction sensitivities were: 85·4% (95% CI 70·8–94·4) for isoniazid, 73·3% (44·9–92·2) for rifampicin, 50·0% (21·1–78·9) for ethambutol, and 57·1% (34·0–78·2) for pyrazinamide; all specificities were more than 99·6%. Sensitivity values were lower than previously reported, but the overall pan-susceptibility accuracy was 96·4%. Genotypic analysis revealed that four phenotypically susceptible isolates carried mutations (rpoB Leu430Pro and rpoB Ile491Phe for rifampicin and fabG1 Leu203Leu for isoniazid) known to give borderline resistance in standard phenotypic tests. Additionally, we identified three putative resistance-associated mutations (inhA Ser94Ala, katG Leu48Pro, and katG Gly273Arg for isoniazid) in samples with substantially higher MICs than those of susceptible isolates. Combining both genomic and phenotypic data, in accordance with the WHO diagnostic guidelines, we could detect two new multidrug-resistant cases. Additionally, we detected 11 (1·6%) of 706 isolates to be monoresistant to fluoroquinolone, which had been previously undetected. Interpretation: We showed that the WHO catalogue enables the detection of resistant cases missed in phenotypic testing in a low-burden region, thus allowing for better patient-tailored treatment. We also identified mutations not included in the catalogue, relevant at the local level. Evidence from this study, together with future updates of the catalogue, will probably lead in the future to the partial replacement of culture testing with WGS-based drug susceptibility testing in our setting. Funding: European Research Council and the Spanish Ministerio de Ciencia.This project received funding from the European Research Council under the European Union’s Horizon 2020 Research and Innovation Program Grant 101001038 (TB-RECONNECT; awarded to IC), from Ministerio de Ciencia (Spanish Government) Project PID2019-104477RB-I00 (awarded to IC), and from Generalitat Valenciana Project AICO/2018/113 (awarded to IC). AMG-M is funded by a Formación deProfesorado Universitario grant programme (FPU19/04562) from Ministerio de Universidades (Spanish Government). IC is also supported by the European Commission–NextGenerationEU, through Centro Superior de Investigaciones Científicas Global Health Platform (PTI Salud Global). We thank all the members of the Valencia RegionTuberculosis Working Group

Novel Spike-stabilized trimers with improved production protect K18-hACE2 mice and golden Syrian hamsters from the highly pathogenic SARS-CoV-2 Beta variant

Most COVID-19 vaccines are based on the SARS-CoV-2 Spike glycoprotein (S) or their subunits. However, S shows some structural instability that limits its immunogenicity and production, hampering the development of recombinant S-based vaccines. The introduction of the K986P and V987P (S-2P) mutations increases the production and immunogenicity of the recombinant S trimer, suggesting that these two parameters are related. Nevertheless, S-2P still shows some molecular instability and it is produced with low yield. Here we described a novel set of mutations identified by molecular modeling and located in the S2 region of the S-2P that increase its production up to five-fold. Besides their immunogenicity, the efficacy of two representative S-2P-based mutants, S-29 and S-21, protecting from a heterologous SARS-CoV-2 Beta variant challenge was assayed in K18-hACE2 mice (an animal model of severe SARS-CoV-2 disease) and golden Syrian hamsters (GSH) (a moderate disease model). S-21 induced higher level of WH1 and Delta variants neutralizing antibodies than S-2P in K18-hACE2 mice three days after challenge. Viral load in nasal turbinate and oropharyngeal samples were reduced in S-21 and S-29 vaccinated mice. Despite that, only the S-29 protein protected 100% of K18-hACE2 mice from severe disease. When GSH were analyzed, all immunized animals were protected from disease development irrespectively of the immunogen they received. Therefore, the higher yield of S-29, as well as its improved immunogenicity and efficacy protecting from the highly pathogenic SARS-CoV-2 Beta variant, pinpoint the S-29 mutant as an alternative to the S-2P protein for future SARS-CoV-2 vaccine development

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

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe

Life cycle assessment of alternative processes to treat fly ash from waste incineration

Grado en Ingeniería Químic

Environmental performance of alternatives to treat fly ash from a waste to energy plant

Incineration has been adopted by many developed countries as an alternative to treat municipal solid waste due to its capacity to reduce the amount of waste and recover energy. Waste to energy plants produce two waste streams: bottom ashes and fly ashes (FA). FA are classified as hazardous waste, and they cannot be utilised or landfilled without prior treatment. Stabilisation with cement solidification is the most used method to treat FA because it achieves the immobilisation of pollutants at a relatively low cost. However, the accelerated carbonation of FA, which allows the encapsulation of certain mobile metals under alkaline conditions, has recently been proposed as an alternative to the solidification/stabilisation process. To determine the environmental performance of FA stabilisation and carbonation, a life cycle assessment (LCA) was conducted. The LCA results of the carbonation and stabilisation processes were compared, and multiple carbonation scenarios were analysed: carbonation with different CO2sources (incineration flue gas and flue gas from the combustion of natural gas), and different pressures (1–5 bar) and percentages of CO2 excess (10%, 55% and 100%) in the flue gas stream. Stabilisation had higher environmental impacts than carbonation due mainly to cement production and consumption. The best operating conditions of the carbonation process were found at flue gas pressures between 3 and 5 bar, since the total energy consumption decreases as the pressure increases. Moreover, the environmental benefits associated with the substitution of electricity from the grid mix made the scenarios based on the combustion of natural gas perform better than those that use the incineration gases as a CO2 source

Immunization with V987H-stabilized Spike glycoprotein protects K18-hACE2 mice and golden Syrian hamsters upon SARS-CoV-2 infection

Safe and effective severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) vaccines are crucial to fight against the coronavirus disease 2019 pandemic. Most vaccines are based on a mutated version of the Spike glycoprotein [K986P/V987P (S-2P)] with improved stability, yield and immunogenicity. However, S-2P is still produced at low levels. Here, we describe the V987H mutation that increases by two-fold the production of the recombinant Spike and the exposure of the receptor binding domain (RBD). S-V987H immunogenicity is similar to S-2P in mice and golden Syrian hamsters (GSH), and superior to a monomeric RBD. S-V987H immunization confer full protection against severe disease in K18-hACE2 mice and GSH upon SARS-CoV-2 challenge (D614G or B.1.351 variants). Furthermore, S-V987H immunized K18- hACE2 mice show a faster tissue viral clearance than RBD- or S-2P-vaccinated animals challenged with D614G, B.1.351 or Omicron BQ1.1 variants. Thus, S-V987H protein might be considered for future SARS-CoV-2 vaccines development.This work was supported by Grifols pharmaceutical, the CERCA Program (2021 SGR 00452 to B.C.; Generalitat de Catalunya), Direcció General de Recerca i Innovació en Salut (Generalitat de Catalunya) (projects SLD0015 to J.C. and SLD0016 to J.B.), the Carlos III Health Institute (PI17/ 01518 to J.B. and PI18/01332 to J.C.). J.B. is supported by the Health Department of the Catalan Government (Generalitat de Catalunya). In addition, the project was also supported by the crowdfunding projects “YomeCorono” (to A.V., V.G., J.C., B.C., J.B. and N.I.-U.), BonPreu/Esclat, and Correos (to J.B.). CAN was supported by a predoctoral grant from Generalitat de Catalunya and Fons Social Europeu (2020 FI_B_0742). A.P.G. was supported by a predoctoral grant from Generalitat de Catalunya and Fons Social Europeu (2022 FI_B_00698). P.A.R. was funded by a predoctoral fellowship from the Government of Catalonia (2020FI_B2_00138). E.P. was supported by a doctoral grant from National Agency for Research and Development of Chile (ANID: 72180406). N.I.-U. is supported by the Spanish Ministry of Science and Innovation (grant PID2020-117145RB-I00), EU HORIZON-HLTH-2021- CORONA-01 (grant 101046118). This study was also supported by CIBER—Consorcio Centro de Investigación Biomédica en Red (CB 2021), Carlos III Health Institute, Ministerio de Ciencia e Innovación and Unión Europea—NextGenerationEU. We would like to thank Foundation Dormeur that support the acquisition of the QuantStudio-5 real time PCR system, an Eclipse Ts2R-FL Inverted Research Microscope, and an ÄKTA go protein purification system. Funders had no role in study design, data analysis, decision to publish, or manuscript preparation. We thank to Ismael Valera, the CMCiB’s staff (Sara Capdevila, Jordi Grifols, Rosa Maria Ampudia, Jorge Diaz, Yaiza Rosales and Sergi Sunye) and the BSL3 IRTA-CReSA staff (Xavier Abad, Ivan Cordon, Anna Pou, Oscar García, Joanna Wiacek, Maria Angeles Osuna, Luís Ribas and Claudia Pereira Sunyé) for their technical assistance with in vivo animal studies.info:eu-repo/semantics/publishedVersio