26 research outputs found

    Potential of implementation of residential photovoltaics at city level: the case of London

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    In recent years, reductions in the price of photovoltaic panels and batteries have made them profitable. However, the achievement of grid parity, i.e. whether these systems are cheaper than the national grid for residential users, is still being debated. This paper quantifies the proportion of demand that could be covered assuming that solar-battery adoption is decided based on the maximum profit, the maximum autarky with no extra cost or the maximum autarky with limited extra-cost. A simulation model is developed which performs a half-hourly analysis for one year, considering the solar radiation, the consumption pattern and characteristics of equipment. London is examined using a database gathering consumption from 5567 households. In particular, the techno-economic performance of the systems is studied according to different reward schemes (from a non-subsidized to a high compensation one). Results are discussed according to the optimisation strategy: maximising profit, for users seeking economic performance; and maximum autarky, for users willing independence from the grid. Complementarily, the correlation between characteristics of consumption profiles and autarky is analysed. Results show that installations are profitable for a reward of 0.03 ÂŁ/kWh, under profit maximisation, and can attain 90% autarky. The injection reward is still essential to make batteries profitable.Peer ReviewedPostprint (published version

    Specialized proresolving mediators protect against experimental autoimmune myocarditis by modulating Ca2+ handling and NRF2 activation

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    Specialized proresolving mediators and, in particular, 5(S), (6)R, 7-trihydroxyheptanoic acid methyl ester (BML-111) emerge as new therapeutic tools to prevent cardiac dysfunction and deleterious cardiac damage associated with myocarditis progression. The cardioprotective role of BML-111 is mainly caused by the prevention of increased oxidative stress and nuclear factor erythroid-derived 2-like 2 (NRF2) down-regulation induced by myocarditis. At the molecular level, BML-111 activates NRF2 signaling, which prevents sarcoplasmic reticulum–adenosine triphosphatase 2A down-regulation and Ca2+ mishandling, and attenuates the cardiac dysfunction and tissue damage induced by myocarditis.This work was supported by the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund (SAF-2017-84777R), Instituto de Salud Carlos III (ISCIII) (PI17/01093, PI17/01344, and PI20/01482), Sociedad Española de CardiologĂ­a, Proyecto Traslacional 2019 and AsociaciĂłn del Ritmo Cardiaco (SEC, España), Proyecto AsociaciĂłn Insuficiencia Cardiaca (Trasplante Cardiaco) 2020, Fondo Europeo de Desarrollo Regional, Fondo Social Europeo, and CIBERCV, a network funded by ISCIII, Spanish Ministry of Science, Innovation and Universities (PGC2018-097019-B-I00), Ministerio de EconomĂ­a, Industria y Competitividad/Agencia Estatal de InvestigaciĂłn 10.13039/501100011033 PID2020-113238RB-I00, PID2019-105600RB-I00, the Instituto de Salud Carlos III (Fondo de InvestigaciĂłn Sanitaria grant PRB3 [PT17/0019/0003-ISCIII-SGEFI/ERDF, ProteoRed]), and “la Caixa” Foundation (project code HR17-00247). The Centro Nacional de Investigaciones Cardiovasculares is supported by the ISCIII, the Ministerio de Ciencia, InnovaciĂłn y Universidades. Dr Ruiz-Hurtado is Miguel Servet I researcher of ISCIII (CP15/00129 Carlos III Health Institute). Dr Tamayo and R.I. JaĂ©n, and M. Gil-FernĂĄndez were or currently are PhD students funded by the FormaciĂłn de Profesorado Universitario program of the Spanish Ministry of Science, Innovation and Universities (FPU17/06135; FPU16/00827, FPU1901973)

    Differential expression of genes mapping to recurrently abnormal chromosomal regions characterize neuroblastic tumours with distinct ploidy status

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    <p>Abstract</p> <p>Background</p> <p>Neuroblastic tumours (NBTs) represent a heterogeneous spectrum of neoplastic diseases associated with multiple genetic alterations. Structural and numerical chromosomal changes are frequent and are predictive parameters of NBTs outcome. We performed a comparative analysis of the biological entities constituted by NBTs with different ploidy status.</p> <p>Methods</p> <p>Gene expression profiling of 49 diagnostic primary NBTs with ploidy data was performed using oligonucleotide microarray. Further analyses using Quantitative Real-Time Polymerase Chain Reaction (Q-PCR); array-Comparative Genomic Hybridization (aCGH); and Fluorescent <it>in situ </it>Hybridization (FISH) were performed to investigate the correlation between aneuploidy, chromosomal changes and gene expression profiles.</p> <p>Results</p> <p>Gene expression profiling of 49 primary near-triploid and near-diploid/tetraploid NBTs revealed distinct expression profiles associated with each NBT subgroup. A statistically significant portion of genes mapped to 1p36 (<it>P </it>= 0.01) and 17p13-q21 (<it>P </it>< 0.0001), described as recurrently altered in NBTs. Over 90% of these genes showed higher expression in near-triploid NBTs and the majority are involved in cell differentiation pathways. Specific chromosomal abnormalities observed in NBTs, 1p loss, 17q and whole chromosome 17 gains, were reflected in the gene expression profiles. Comparison between gene copy number and expression levels suggests that differential expression might be only partly dependent on gene copy number. Intratumoural clonal heterogeneity was observed in all NBTs, with marked interclonal variability in near-diploid/tetraploid tumours.</p> <p>Conclusion</p> <p>NBTs with different cellular DNA content display distinct transcriptional profiles with a significant portion of differentially expressed genes mapping to specific chromosomal regions known to be associated with outcome. Furthermore, our results demonstrate that these specific genetic abnormalities are highly heterogeneous in all NBTs, and suggest that NBTs with different ploidy status may result from different mechanisms of aneuploidy driving tumourigenesis.</p

    Differential expression of genes mapping to recurrently abnormal chromosomal regions characterize neuroblastic tumours with distinct ploidy status

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    <p>Abstract</p> <p>Background</p> <p>Neuroblastic tumours (NBTs) represent a heterogeneous spectrum of neoplastic diseases associated with multiple genetic alterations. Structural and numerical chromosomal changes are frequent and are predictive parameters of NBTs outcome. We performed a comparative analysis of the biological entities constituted by NBTs with different ploidy status.</p> <p>Methods</p> <p>Gene expression profiling of 49 diagnostic primary NBTs with ploidy data was performed using oligonucleotide microarray. Further analyses using Quantitative Real-Time Polymerase Chain Reaction (Q-PCR); array-Comparative Genomic Hybridization (aCGH); and Fluorescent <it>in situ </it>Hybridization (FISH) were performed to investigate the correlation between aneuploidy, chromosomal changes and gene expression profiles.</p> <p>Results</p> <p>Gene expression profiling of 49 primary near-triploid and near-diploid/tetraploid NBTs revealed distinct expression profiles associated with each NBT subgroup. A statistically significant portion of genes mapped to 1p36 (<it>P </it>= 0.01) and 17p13-q21 (<it>P </it>< 0.0001), described as recurrently altered in NBTs. Over 90% of these genes showed higher expression in near-triploid NBTs and the majority are involved in cell differentiation pathways. Specific chromosomal abnormalities observed in NBTs, 1p loss, 17q and whole chromosome 17 gains, were reflected in the gene expression profiles. Comparison between gene copy number and expression levels suggests that differential expression might be only partly dependent on gene copy number. Intratumoural clonal heterogeneity was observed in all NBTs, with marked interclonal variability in near-diploid/tetraploid tumours.</p> <p>Conclusion</p> <p>NBTs with different cellular DNA content display distinct transcriptional profiles with a significant portion of differentially expressed genes mapping to specific chromosomal regions known to be associated with outcome. Furthermore, our results demonstrate that these specific genetic abnormalities are highly heterogeneous in all NBTs, and suggest that NBTs with different ploidy status may result from different mechanisms of aneuploidy driving tumourigenesis.</p

    Cocoa, Hazelnuts, Sterols and Soluble Fiber Cream Reduces Lipids and Inflammation Biomarkers in Hypertensive Patients: A Randomized Controlled Trial

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    Cocoa, mixed with other food ingredients, intake can have beneficial effects on cardiovascular disease (CVD) biomarkers. We compared the effects of 4 cocoa cream products on some of these biomarkers.In this multi-centered, randomized, controlled, double-blind, parallel trial, volunteers (n = 113; age range: 43-65 years) who were pre-hypertensive, stage-1 hypertensive and hypercholesterolemic received one of 4 cocoa cream products (13 g/unit; 1 g cocoa/unit, 6 units/d; 465 Kcal/d) added to a low saturated fat diet for 4 weeks. The groups were: A) (n = 28), cocoa cream considered as control; B) (n = 28), cocoa+hazelnut cream (30 g/d hazelnuts); C) (n = 30), cocoa+hazelnuts+phytosterols (2 g/d); and D) (n = 27), cocoa+hazelnuts+phytosterols+soluble fiber (20 g/d) the patented "LMN product". Primary outcome measures were BP, LDL-c, apolipoprotein B-100 (Apo B), ApoB/ApoA ratio, oxidized LDL (oxLDL) and high-sensitive C-reactive protein (hsCRP) determined at baseline and post-cocoa cream product intake. Statistical analysis used was ANCOVA or mixed models (in case of repeated measurements), with baseline observation included as a covariate. After 4 weeks, compared to product A, product C reduced LDL-c by 11.2%, Apo B by 8.1% and ApoB/ApoA ratio by 7.8% (P = 0.01). LMN decreased LDL-c by 9.2%, Apo B-100 by 8.5%, ApoB/ApoA ratio by 10.5%, hsCRP by 33.4% and oxLDL by 5.9% (P = 0.01). Surprisingly, even "control" product A reduced systolic BP (-7.89 mmHg; 95%CI: -11.45 to -4.3) and diastolic BP (-5.54 mmHg; 95%CI: -7.79 to -3.29). The BP reductions were similar with the other 3 products. Limitations of the study are that the trial period was relatively short and that a better "BP control" product would have been preferable.The creams (particularly the LMN) have anti-inflammatory and antioxidant effects in addition to lowering LDL-c, Apo B and ApoB/ApoA ratio. Thus, the soluble fiber effects amplified with sterols (as contained in the cocoa creams) provide new dietary therapeutic perspectives.Clinicaltrials.gov NCT00511420

    Randomized-controlled trial of the DIALIVE liver dialysis device vs. standard of care in patients with acute-on-chronic liver failure

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    BACKGROUND AND AIMS: Acute on chronic liver failure (ACLF) is characterized by severe systemic inflammation, multi-organ failure and high mortality rates. Its treatment is an urgent unmet need. DIALIVE is a novel liver dialysis device that aims to exchange d ysfunctional albumin and remove damage- and pathogen-associated molecular patterns. This first-in-man randomized, controlled clinical trial was performed with the primary aim of assessing its safety in ACLF patients with secondary aims to evaluate its clinical effects, device performance and effect on pathophysiologically-relevant biomarkers. METHODS: 32 alcoholic cirrhosis patients with ACLF were included. Patients were treated with DIALIVE for up to 5-days and end points were assessed at Day-10. Safety was assessed in all patients (n=32). The secondary aims were assessed in a pre-specified subgroup that had at least 3-treatment sessions with DIALIVE (n=30). RESULTS: There were no significant differences in 28-day mortality or occurrence of serious adverse events between the groups. Significant reduction in the severity of endotoxemia and improvement in albumin function was observed in DIALIVE group, which translated into a significant reduction in the CLIF-C (Chronic Liver Failure consortium) organ failure (p=0.018) and CLIF-C ACLF scores (p=0.042) at Day-10. Time to resolution of ACLF was significantly faster in DIALIVE group (p=0.036). Biomarkers of systemic inflammation such as IL-8 (p=0.006), cell death [cytokeratin-18: M30 (p=0.005) and M65 (p=0.029)], endothelial function [asymmetric dimethylarginine (p=0.002)] and, ligands for toll-like receptor 4 (p=0.030) and inflammasome (p=0.002) improved significantly in DIALIVE group. CONCLUSIONS: These data indicate that DIALIVE appears to be safe and impacts positively on prognostic scores and pathophysiologically relevant biomarkers in patients with ACLF. Larger, adequately powered studies are warranted to further confirm its safety and efficacy. LAY SUMMARY: This is the first-in-man clinical trial which tested DIALIVE, a novel liver dialysis device for the treatment of liver cirrhosis and acute on chronic liver failure, a condition associated with severe inflammation, organ failures and a high risk of death. The study met the primary end point confirming DIALIVE system to be safe. Additionally, it reduced inflammation with improved clinical parameters. It did not, however, reduce mortality in this small study and requires further larger clinical trials to re-confirm its safety and evaluate efficacy. CLINICAL TRIAL NUMBER: NCT03065699

    Specific gene expression profiles and chromosomal abnormalities are associated with infant disseminated neuroblastoma

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    Background: Neuroblastoma (NB) tumours have the highest incidence of spontaneous remission, especially among the stage 4s NB subgroup affecting infants. Clinical distinction of stage 4s from lethal stage 4 can be difficult, but critical for therapeutic decisions. The aim of this study was to investigate chromosomal alterations and differential gene expression amongst infant disseminated NB subgroups. Methods: Thirty-five NB tumours from patients diagnosed at < 18 months (25 stage 4 and 10 stage 4s), were evaluated by allelic and gene expression analyses. Results: All stage 4s patients underwent spontaneous remission, only 48% stage 4 patients survived despite combined modality therapy. Stage 4 tumours were 90% near-diploid/tetraploid, 44% MYCN amplified, 77% had 1p LOH (50% 1p36), 23% 11q and/or 14q LOH (27%) and 47% had 17q gain. Stage 4s were 90% near-triploid, none MYCN amplified and LOH was restricted to 11q. Initial comparison analyses between stage 4s and 4 < 12 months tumours revealed distinct gene expression profiles. A significant portion of genes mapped to chromosome 1 (P < 0.0001), 90% with higher expression in stage 4s, and chromosome 11 (P = 0.0054), 91% with higher expression in stage 4. Less definite expression profiles were observed between stage 4s and 4 < 18m, yet, association with chromosomes 1 (P < 0.0001) and 11 (P = 0.005) was maintained. Distinct gene expression profiles but no significant association with specific chromosomal region localization was observed between stage 4s and stage 4 < 18 months without MYCN amplification. Conclusion: Specific chromosomal aberrations are associated with distinct gene expression profiles which characterize spontaneously regressing or aggressive infant NB, providing the biological basis for the distinct clinical behaviour
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