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- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 4. |
- García, Antonio, et al.
(författare)
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Combining in-cylinder pressure and 1D simulation tools to understand the combustion characteristics of natural gas in pre-chamber ignition systems for energy generation
- 2021
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Ingår i: Energy Conversion and Management. - : Elsevier BV. - 0196-8904. ; 240
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Tidskriftsartikel (refereegranskat)abstract
- Recent outlooks suggest a long-term relevance of internal combustion engines for both power generation and transportation. Nonetheless, stringent pollutant reduction requirements combined with new CO2 mandates draws a challenging scenario, requiring intensive research and development activities to develop and optimize combustion modes to fulfill these requirements. Among the recent advancements, the active pre-chamber ignition system has been considered as a potential alternative to achieve a highly efficient and clean combustion process. Its combustion development is dictated by the pre-chamber ignition system which will provides a high energy flow jet inside the main chamber to enable a multi-site oxidation of the global lean mixture. The comprehension and quantification of the flow and combustion characteristics of the pre-chamber are of utmost importance to optimize the engine operation and pre-chamber design. Nonetheless, restrictive space for instrumentation at experimental side requires alternative numerical methods to aid the quantification of the state parameters and combustion process of these systems. In this sense, this research proposes a novel methodology combining in-cylinder pressure measurement and 1-D simulations as a tool to determine the state, flow and combustion development of different active pre-chambers operating with natural gas in a heavy-duty engine for power generation. The methodology is developed considering 3 different pre-chamber geometries, operating at different spark timings and equivalence ratios. The results suggest that the methodology is able to quantify the state conditions prior to the spark discharge as well as the evolution of the combustion process by means of considering the perturbations of the mass flow from the pre-chamber inside the main chamber energy balance. Moreover, the methodology allowed to quantify variations of equivalence ratio as small as 0.1 and combustion durations variations of 1 CAD.
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| 6. |
- Huybrechts, I, et al.
(författare)
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Evaluation of the Children's Eating Habits Questionnaire used in the IDEFICS study by relating urinary calcium and potassium to milk consumption frequencies among European children
- 2011
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Ingår i: Int J Obesity. - : Springer Science and Business Media LLC. - 0307-0565. ; 35, suppl 1, s. 69-78
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Tidskriftsartikel (refereegranskat)abstract
- Background: Measuring dietary intake in children is notoriously difficult. Therefore, it is crucial to evaluate the performance of dietary intake assessment methods in children. Given the important contribution of milk consumption to calcium (Ca) and potassium (K) intakes, urinary calcium (UCa) and potassium (UK) excretions in spot urine samples could be used for estimating correlations with milk consumption frequencies. Objective: The aim of this study was to evaluate the assessment of milk consumption frequencies derived from the Food Frequency Questionnaire section of the Children's Eating Habits Questionnaire (CEHQ-FFQ) used in the IDEFICS (Identification and prevention of dietary- and lifestyle induced health effects in children and infants) study by comparing with UCa and UK excretions in spot urine samples. Design: This study was conducted as a setting-based community-oriented intervention study and results from the first cross-sectional survey have been included in the analysis. Subjects: A total of 10309 children aged 2–10 years from eight European countries are included in this analysis. Methods: UCa and UK excretions were measured in morning spot urine samples. Calcium and potassium urine concentrations were standardised for urinary creatinine (Cr) excretion. Ratios of UCa/Cr and UK/Cr were used for multivariate regression analyses after logarithmic transformation to obtain normal distributions of data. Milk consumption frequencies were obtained from the CEHQ-FFQ. Multivariate regression analyses were used to investigate the effect of milk consumption frequencies on UCa and UK concentrations, adjusting for age, gender, study centre, soft drink consumption and frequency of main meals consumed at home. Results: A significant positive correlation was found between milk consumption frequencies and ratios of UK/Cr and a weaker but still significant positive correlation with ratios of UCa/Cr, when using crude or partial Spearman's correlations. Multivariate regression analyses showed that milk consumption frequencies were predictive of UCa/Cr and UK/Cr ratios, when adjusted for age, gender, study centre, soft drink consumption and frequency of main meals consumed at home. Mean ratios of UK/Cr for increasing milk consumption frequency tertiles showed a progressive increase in UK/Cr. Children consuming at least two milk servings per day had significantly higher mean UCa/Cr and UK/Cr ratios than children who did not. Large differences in correlations between milk consumption frequencies and ratios of UCa/Cr and UK/Cr were found between the different study centres. Conclusion: Higher milk consumption frequencies resulted in a progressive increase in UK/Cr and UCa/Cr ratios, reflecting the higher Ca and K intakes that coincide with increasing milk consumption, which constitutes a major K and Ca source in children's diet.
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| 7. |
- Onofrio, Gessica, et al.
(författare)
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Experimental and Numerical Assessment of Active Pre-chamber Ignition in Heavy Duty Natural Gas Stationary Engine
- 2020
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Ingår i: WCX SAE World Congress Experience. - 400 Commonwealth Drive, Warrendale, PA, United States : SAE International. - 0148-7191. ; 2020-April
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Konferensbidrag (refereegranskat)abstract
- Gas engines (fuelled with CNG, LNG or Biogas) for generation of power and heat are, to this date, taking up larger shares of the market with respect to diesel engines. In order to meet the limit imposed by the TA-Luft regulations on stationary engines, lean combustion represents a viable solution for achieving lower emissions as well as efficiency levels comparable with diesel engines. Leaner mixtures however affect the combustion stability as the flame propagation velocity and consequently heat release rate are slowed down. As a strategy to deliver higher ignition energy, an active pre-chamber may be used. This work focuses on assessing the performance of a pre-chamber combustion configuration in a stationary heavy-duty engine for power generation, operating at different loads, air-to-fuel ratios and spark timings. The engine was originally a 6-cylinder compression ignition engine which is here employed as a single cylinder engine and then suitably modified to host the pre-chamber (with its natural gas injection system and spark plug) with a new bowl piston to decrease compression ratio. A 0D model is built to make a thermodynamic analysis to characterize the local conditions in the pre-chamber before spark timing (temperature, pressure and composition), based on a compressible nozzle equation for the mass transfer between the chambers and a simplified Woschni model for the pre-chamber's heat transfer. A mathematical expression was found to describe the relationship between the local conditions and the early stage of the combustion. Experimental results showed the beneficial effect of spark delay and mixture leaning for the reduction of NOx emissions, while CO, unburned hydrocarbons and engine performance see improvement with lower air-to-fuel ratios and spark advance.
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| 8. |
- Papareddy, Praveen, et al.
(författare)
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A human antithrombin isoform dampens inflammatory responses and protects from organ damage during bacterial infection
- 2019
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Ingår i: Nature Microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 4:12, s. 2442-2455
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Tidskriftsartikel (refereegranskat)abstract
- Severe infectious diseases are often characterized by an overwhelming and unbalanced systemic immune response to microbial infections. Human antithrombin (hAT) is a crucial coagulation inhibitor with anti-inflammatory activities. Here we identify three hAT-binding proteins (CD13, CD300f and LRP-1) on human monocytes that are involved in blocking the activity of nuclear factor-kappa B. We found that the modulating effect is primarily restricted to the less abundant beta-isoform (h beta AT) of hAT that lacks N-glycosylation at position 135. Individuals with a mutation at this position have increased production of h beta AT and analysis of their blood, which was stimulated ex vivo with lipopolysaccharide, showed a decreased inflammatory response. Similar findings were recorded when heterozygotic mice expressing hAT or h beta AT were challenged with lipopolysaccharide or infected with Escherichia coli bacteria. Our results finally demonstrate that in a lethal E. coli infection model, survival rates increased when mice were treated with h beta AT one hour and five hours after infection. The treatment also resulted in a reduction of the inflammatory response and less severe organ damage.
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| 9. |
- Podadera, I., et al.
(författare)
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COMMISSIONING PLAN OF THE IFMIF-DONES ACCELERATOR
- 2022
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Ingår i: LINAC 2022 - International Linear Accelerator Conference, Proceedings. - 2226-0366. - 9783954502158 ; , s. 331-334
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Konferensbidrag (refereegranskat)abstract
- IFMIF-DONES (International Fusion Materials Irradiation Facility- DEMO-Oriented Neutron Early Source) - a powerful neutron irradiation facility for studies and certification of materials to be used in fusion reactors - is planned as part of the European roadmap to fusion electricity. Its main goal will be to characterize and to qualify materials under irradiation in a neutron field similar to the one faced in a fusion reactor. The intense neutron source is produced by impinging deuterons, from high-power linear deuteron accelerator, on a liquid lithium curtain. The facility has accomplished the preliminary design phase and is currently in its detailed design phase. At the present stage, it is important to have a clear understanding of how the commissioning of the facility will be performed, especially the commissioning of a 5 MW CW deuteron beam, together with the lithium curtain and the beam optimization for the neutron irradiation. In this contribution, the present plans for the hardware and beam commissioning of the accelerator will be given, focusing on the most critical aspects of the tiered approach and on the integration of the procedure with the lithium and test systems.
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