Modelling challenges of stationary combustion in inert porous media

Thanks to strong heat recirculation, submerged combustion within porous media presents unique technological features such as broadened flammability limits and extended power range. The associated possibility to burn ultra-lean mixtures with minimal CO/NOx emissions makes porous media combustion a potential alternative in the industry, for instance in domestic heat generation or clean aviation where low pollutant emissions and robust operability are of paramount importance. However, even though this combustion mode has been studied for decades, there remains many open questions regarding the intertwined flame structure and the validity of associated low-order modelling. To date, volume-averaged models are mostly based upon ad hoc hypotheses and still present large discrepancies with experiments. Aiming to chal- lenge and strengthen these models, the present work presents analytical and numerical studies of the volume-averaged equations, followed by 3D direct pore-level simulations of methane-air and hydrogen-air combustion. Chapters 1 and 2 provide a critical review of concepts associated to flows and flames within porous media, with a focus on non-adiabatic combustion and macroscopic effective characteriza- tion. A classification of gaseous flames in terms of the thermal Péclet number is proposed, and the upscaling procedure on the pointwise equations is presented. Chapter 3 presents asymptotic results based on the volume-averaged equations, and the proposed theoretical framework un- veils the first fully-explicit formulae for flame speed in infinite and finite-length porous burners. Multi-layered burners are also considered theoretically for the first time, and the important con- cept of contact resistance between two stacked porous plates is underlined. Chapter 4 proposes a general classification of porous media combustion in three distinct regimes for increasing inter- phase heat transfer, only based on two reduced parameters, in order to reconcile the literature frameworks of local thermal equilibrium (LTE) and non-equilibrium (LTNE). Chapter 5, 6 and 7 present 3D pore-level direct numerical simulations of flames within porous media using complex kinetics, for various structural topologies and pore sizes. As a major technical hurdle encountered during the thesis, the meshing workflow from X-ray tomography to conformal computational mesh is given for practical use in the community. These DNS unveil the internal flame structure of methane-air and hydrogen-air flames within typical porous burners, and it is shown that when the pore size is larger than the flame thickness, sharp and locally- anchored flame fronts are observed. These local discontinuities related to the strongly non-linear reaction rates are shown to be in direct violation of the classical volume-averaged hypotheses. This demonstrates that new volume-averaged models are required, and accordingly a closure for reaction rates based upon phenomenology and observations in the 3D DNS is proposed. Eventually, the pore-level specificities of hydrogen combustion at pore scale are described

Fully explicit formulae for flame speed in infinite and finite porous media

This work proposes new analytical expressions for gaseous flames in inert porous media, based on the existing modelling strategies. The central hypothesis is that interphase heat transfer has negligible impact on the local flame structure. This requires a gradual separation between the length scales of chemical reactions, gas diffusion, and interphase thermal re-equilibriation. By resolving the gas and solid equations without reaction on each side of the reaction sheet, the preheating of the fresh gases ahead of the flame front is analytically computed at leading order. Combustion kinetics are solved separately, assuming the consumption rate to be a sole function of this preheating. Two kinetic models are considered, namely, single-step Arrhenius and power law fits from experiments or detailed computations. Several fully explicit formulae for flame speed in porous media are given accordingly. A universal abacus provides the maximum flame speed attainable in finite porous media. The explicit, ready-to-use nature of the present theory is particularly suitable for practical designs. This work is consistent with previous theoretical, numerical and experimental trends of the literature

Stratégies de modélisation de la combustion stationnaire en milieu poreux inerte

Porous media combustion consists in submerging a flame inside a tortuous solid matrix. The solid, once heated up, holds the flame in an environment hotter than free air, which accelerates reaction kinetics. This effect is referred to as heat recirculation, and allows to burn mixtures of very low fuel content with minimal pollutant emissions. This work focuses on the macroscopic and microscopic quantification of this phenomenon. At the macroscopic scale, a theoretical work is performed on the volume-averaged equations, unveiling the first fully-explicit formulae for submerged flame speed. At the microscopic scale, detailed numerical simulations reveal the convoluted, intertwined nature of the internal flame front. The influence of volume-averaging is then described and quantified, and it is shown that current models are not adapted to cases where the pore size is larger than the flame thickness – although typical of most industrial burners.La combustion en milieu poreux consiste à immerger une flamme dans une matrice solide tortueuse. Le solide, réchauffé, maintient la flamme dans un environnement plus chaud que l’air libre, ce qui accélère la cinétique de réaction. On parle alors de recirculation de chaleur - qui permet de brûler des mélanges très pauvres et moins polluants. Cette thèse s’intéresse à la quantification macroscopique et microscopique de ce phénomène. A l’échelle macroscopique, un travail théorique est mené sur les équations filtrées en volume, révélant notamment des formules théoriques explicites pour la vitesse de flamme immergée. A l’échelle microscopique, des simulations numériques détaillées révèlent la nature convoluée du front de flamme interne. L’impact du filtrage en volume est évalué qualitativement et quantitativement, et l’on montre que lorsque l’épaisseur de flamme est plus petite que la taille des pores, les modèles actuels échouent à prédire le comportement de la combustion poreuse

Stratégies de modélisation de la combustion stationnaire en milieu poreux inerte

La combustion en milieu poreux consiste à immerger une flamme dans une matrice solide tortueuse. Le solide, réchauffé, maintient la flamme dans un environnement plus chaud que l’air libre, ce qui accélère la cinétique de réaction. On parle alors de recirculation de chaleur - qui permet de brûler des mélanges très pauvres et moins polluants. Cette thèse s’intéresse à la quantification macroscopique et microscopique de ce phénomène. A l’échelle macroscopique, un travail théorique est mené sur les équations filtrées en volume, révélant notamment des formules théoriques explicites pour la vitesse de flamme immergée. A l’échelle microscopique, des simulations numériques détaillées révèlent la nature convoluée du front de flamme interne. L’impact du filtrage en volume est évalué qualitativement et quantitativement, et l’on montre que lorsque l’épaisseur de flamme est plus petite que la taille des pores, les modèles actuels échouent à prédire le comportement de la combustion poreuse.Porous media combustion consists in submerging a flame inside a tortuous solid matrix. The solid, once heated up, holds the flame in an environment hotter than free air, which accelerates reaction kinetics. This effect is referred to as heat recirculation, and allows to burn mixtures of very low fuel content with minimal pollutant emissions. This work focuses on the macroscopic and microscopic quantification of this phenomenon. At the macroscopic scale, a theoretical work is performed on the volume-averaged equations, unveiling the first fully-explicit formulae for submerged flame speed. At the microscopic scale, detailed numerical simulations reveal the convoluted, intertwined nature of the internal flame front. The influence of volume-averaging is then described and quantified, and it is shown that current models are not adapted to cases where the pore size is larger than the flame thickness – although typical of most industrial burners

IMPact of the COVID-19 epidemic on the moRTAlity of kidney transplant recipients and candidates in a French Nationwide registry sTudy (IMPORTANT)

International audienceEnd stage kidney disease increase the risk of COVID-19 related death but how the kidney replacement strategy should be adapted during the pandemic is unknown. Chronic hemodialysis makes social distancing difficult to achieve. Alternatively, kidney transplantation could increase the severity of COVID-19 due to therapeutic immunosuppression and contribute to saturation of intensive care units. For these reasons, kidney transplantation was suspended in France during the first epidemic wave. Here, we retrospectively evaluated this strategy by comparing the overall and COVID-19 related mortality in kidney transplant recipients and candidates over the last three years. Cross-interrogation of two national registries for the period 1 March and 1 June 2020, identified 275 deaths among the 42812 kidney transplant recipients and 144 deaths among the 16210 candidates. This represents an excess of deaths for both populations, as compared with the same period the two previous years (mean of two previous years: 253 in recipients and 112 in candidates). This difference was integrally explained by COVID-19, which accounted for 44% (122) and 42% (60) of the deaths in recipients and candidates, respectively. Taking into account the size of the two populations and the geographical heterogeneity of virus circulation, we found that the excess of risk of death due to COVID-19 was similar for recipients and candidates in high viral risk area but four-fold higher for candidates in the low viral risk area. Thus, in case of a second epidemic wave, kidney transplantation should be suspended in high viral risk areas but maintained outside those areas, both to reduce the excess of deaths of candidates and avoid wasting precious resources

Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial

BackgroundSparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks from the double-blind final analysis.MethodsPROTECT, a double-blind, randomised, active-controlled, phase 3 study, was done across 134 clinical practice sites in 18 countries throughout the Americas, Asia, and Europe. Patients aged 18 years or older with biopsy-proven primary IgA nephropathy and proteinuria of at least 1·0 g per day despite maximised renin–angiotensin system inhibition for at least 12 weeks were randomly assigned (1:1) to receive sparsentan (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral irbesartan once daily) based on a permuted-block randomisation method. The primary endpoint was proteinuria change between treatment groups at 36 weeks. Secondary endpoints included rate of change (slope) of the estimated glomerular filtration rate (eGFR), changes in proteinuria, a composite of kidney failure (confirmed 40% eGFR reduction, end-stage kidney disease, or all-cause mortality), and safety and tolerability up to 110 weeks from randomisation. Secondary efficacy outcomes were assessed in the full analysis set and safety was assessed in the safety set, both of which were defined as all patients who were randomly assigned and received at least one dose of randomly assigned study drug. This trial is registered with ClinicalTrials.gov, NCT03762850.FindingsBetween Dec 20, 2018, and May 26, 2021, 203 patients were randomly assigned to the sparsentan group and 203 to the irbesartan group. One patient from each group did not receive the study drug and was excluded from the efficacy and safety analyses (282 [70%] of 404 included patients were male and 272 [67%] were White) . Patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group. eGFR chronic 2-year slope (weeks 6–110) was −2·7 mL/min per 1·73 m2 per year versus −3·8 mL/min per 1·73 m2 per year (difference 1·1 mL/min per 1·73 m2 per year, 95% CI 0·1 to 2·1; p=0·037); total 2-year slope (day 1–week 110) was −2·9 mL/min per 1·73 m2 per year versus −3·9 mL/min per 1·73 m2 per year (difference 1·0 mL/min per 1·73 m2 per year, 95% CI −0·03 to 1·94; p=0·058). The significant reduction in proteinuria at 36 weeks with sparsentan was maintained throughout the study period; at 110 weeks, proteinuria, as determined by the change from baseline in urine protein-to-creatinine ratio, was 40% lower in the sparsentan group than in the irbesartan group (−42·8%, 95% CI −49·8 to −35·0, with sparsentan versus −4·4%, −15·8 to 8·7, with irbesartan; geometric least-squares mean ratio 0·60, 95% CI 0·50 to 0·72). The composite kidney failure endpoint was reached by 18 (9%) of 202 patients in the sparsentan group versus 26 (13%) of 202 patients in the irbesartan group (relative risk 0·7, 95% CI 0·4 to 1·2). Treatment-emergent adverse events were well balanced between sparsentan and irbesartan, with no new safety signals.InterpretationOver 110 weeks, treatment with sparsentan versus maximally titrated irbesartan in patients with IgA nephropathy resulted in significant reductions in proteinuria and preservation of kidney function

Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial

Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to 1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein-creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850. Findings: Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49·8%) than the irbesartan group (-15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups. Interpretation: Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. Funding: Travere Therapeutics

Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial

Background Sparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks from the double-blind final analysis. Methods PROTECT, a double-blind, randomised, active-controlled, phase 3 study, was done across 134 clinical practice sites in 18 countries throughout the Americas, Asia, and Europe. Patients aged 18 years or older with biopsy-proven primary IgA nephropathy and proteinuria of at least 1·0 g per day despite maximised renin–angiotensin system inhibition for at least 12 weeks were randomly assigned (1:1) to receive sparsentan (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral irbesartan once daily) based on a permuted-block randomisation method. The primary endpoint was proteinuria change between treatment groups at 36 weeks. Secondary endpoints included rate of change (slope) of the estimated glomerular filtration rate (eGFR), changes in proteinuria, a composite of kidney failure (confirmed 40% eGFR reduction, end-stage kidney disease, or all-cause mortality), and safety and tolerability up to 110 weeks from randomisation. Secondary efficacy outcomes were assessed in the full analysis set and safety was assessed in the safety set, both of which were defined as all patients who were randomly assigned and received at least one dose of randomly assigned study drug. This trial is registered with ClinicalTrials.gov, NCT03762850. Findings Between Dec 20, 2018, and May 26, 2021, 203 patients were randomly assigned to the sparsentan group and 203 to the irbesartan group. One patient from each group did not receive the study drug and was excluded from the efficacy and safety analyses (282 [70%] of 404 included patients were male and 272 [67%] were White) . Patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group. eGFR chronic 2-year slope (weeks 6–110) was −2·7 mL/min per 1·73 m2 per year versus −3·8 mL/min per 1·73 m2 per year (difference 1·1 mL/min per 1·73 m2 per year, 95% CI 0·1 to 2·1; p=0·037); total 2-year slope (day 1–week 110) was −2·9 mL/min per 1·73 m2 per year versus −3·9 mL/min per 1·73 m2 per year (difference 1·0 mL/min per 1·73 m2 per year, 95% CI −0·03 to 1·94; p=0·058). The significant reduction in proteinuria at 36 weeks with sparsentan was maintained throughout the study period; at 110 weeks, proteinuria, as determined by the change from baseline in urine protein-to-creatinine ratio, was 40% lower in the sparsentan group than in the irbesartan group (−42·8%, 95% CI −49·8 to −35·0, with sparsentan versus −4·4%, −15·8 to 8·7, with irbesartan; geometric least-squares mean ratio 0·60, 95% CI 0·50 to 0·72). The composite kidney failure endpoint was reached by 18 (9%) of 202 patients in the sparsentan group versus 26 (13%) of 202 patients in the irbesartan group (relative risk 0·7, 95% CI 0·4 to 1·2). Treatment-emergent adverse events were well balanced between sparsentan and irbesartan, with no new safety signals. Interpretation Over 110 weeks, treatment with sparsentan versus maximally titrated irbesartan in patients with IgA nephropathy resulted in significant reductions in proteinuria and preservation of kidney function.</p