Évaluation environnementale des conséquences de la décarbonisation des services énergétiques

Abstract: The services provided by energy commodities are essential for human wellbeing but the reliance on fossil-fuels is jeopardising the livelihood of future generations and ecosystems, through global warming and other cause-effect pathways. There is an urgent need to transform the energy system, but this transformation may create unforeseen problems if not planned comprehensively. Many energy transitions plans rely on energy system optimisation models (ESOM), but these models are ill-prepared to evaluate the range of environmental stressors and their effects, and have oversimplified representations of production systems. An integrative approach combining ESOMs with life cycle assessment (LCA) can overcome the limitations of ESOMs, helping to avoid the ‘backfire’ of mitigation policies. This thesis gives an overview of the limitations of existing approaches linking ESOMs and LCA and implements a novel approach to overcome them. Several questions related to the energy transition in the province of Quebec (Canada) are assessed with the North American TIMES Energy Model (NATEM). The main scenario investigated, modelling the consequences of greenhouse gas (GHG) mitigation targets, is assessed from a life cycle perspective. To link both the optimization and the LCA models, a set of functions and procedures are encoded in an open-source software, that can be reused in other assessments. Results show that just a relatively narrow number of processes drive the changes in GHG, and this feature can be used to simplify the linking between TIMES and LCA models. The integrated ESOM-LCA assessment applied to Quebec indicates that global warming (GW) mitigation policies would reduce impacts on human health and biodiversity. This reduced impact is driven by reduced climate change but also other cause-effect mechanisms such as reduced water scarcity and metal contamination. Additionally, full-year building simulations of Quebec detached houses introduced as new technological options in NATEM suggest that better insulated buildings would reduce the total costs of GW mitigation. The introduction of low-carbon technologies could raise the costs of energy services by 20% but these costs could be substantially lowered with demand-side measures. ESOMs provide an interesting but limited perspective to plan energy transitions. The softlink of ESOMs with LCA is a viable approach to give a more comprehensive view of relative importance of cause-effect pathways affecting human health and biodiversity. The integrated assessment is a powerful tool to analyse a wide range of issues related to the needed energy transitions. Understanding the underlying assumptions and principles of models is also important to interpret and design assessments. To facilitate this kind of analysis, researchers should facilitate the reusability of their works, agreeing on output formats, documenting the code underlying the analyses, and providing tools to integrate models. To this end, scriptable open-source software tools are extremely useful. This thesis attempts to put a step forward in this direction.Les services énergétiques sont essentiels au bien-être humain, mais l’utilisation de combustibles fossiles pour répondre à la demande énergétique compromet les moyens de subsistance des générations futures et des écosystèmes, par le réchauffement climatique et d’autres menaces. Il est donc urgent de transformer le système énergétique existant. Cependant, cette transformation peut créer des problèmes imprévus si elle n’est pas planifiée de manière cohérente et complète. Plusieurs plans de transition énergétique reposent sur des modèles d'optimisation des systèmes énergétiques (MOSE), mais ces modèles sont peu adaptés pour évaluer les facteurs de stress environnementaux et leurs effets, et ils adoptent des représentations trop simplistes des systèmes de production. L’hypothèse de base de cette thèse est qu’une approche combinant les MOSE et l’analyse du cycle de vie (ACV) peut permettre de surmonter les limites des MOSE, en aidant à éviter des imprévus dans les politiques de réduction de gaz à effet de serre. Cette thèse donne un aperçu des limites des approches existantes reliant MOSE et ACV et met en oeuvre une méthodologie possible pour les surmonter. Plusieurs questions liées à la transition énergétique au Québec sont évaluées à l'aide d’un modèle TIMES (NATEM) pour la province de Québec. Le scénario de modélisation des conséquences des objectifs de réduction des gaz à effet de serre (GES) est ensuite évalué selon une perspective de cycle de vie. Pour relier les deux modèles, un ensemble de fonctions et de procédures est codé dans un langage open source (Python), qui peut être réutilisé dans d'autres évaluations. Les résultats montrent que seul un nombre relativement restreint de processus est à l'origine des changements dans la quantité de GES. Cette observation est utilisée pour simplifier la liaison entre les modèles TIMES et ACV. L'évaluation intégrée MOSE-ACV appliquée au Québec indique que les politiques de réduction de GES peuvent réduire les impacts sur la santé humaine et la biodiversité. Cette réduction d’impacts est due à la mitigation du changement climatique, mais également à d'autres mécanismes de cause à effet tels que la réduction de la pénurie d'eau et de la contamination par les métaux. De plus, la liaison des MOSE avec des modèles de simulation énergétique de bâtiments suggère que des bâtiments mieux isolés réduiraient les coûts totaux de réduction de GES. L'introduction de technologies à faibles émissions de carbone pourrait augmenter les coûts des services énergétiques de 20%, mais ces coûts pourraient être considérablement réduits grâce à des mesures axées sur la demande énergétique. Les MOSE offrent une perspective intéressante, mais limitée, pour planifier les transitions énergétiques. La liaison des MOSE avec ACV est une approche viable pour donner une vue plus complète de l’importance relative des mécanismes qui affectent la santé humaine et la biodiversité. L'évaluation intégrée est un outil puissant pour analyser une large gamme de problèmes liés aux transitions énergétiques. Comprendre les hypothèses et principes sous-jacents des modèles est également important pour interpréter les résultats. Pour faciliter ce type d'analyse, les chercheurs doivent faciliter la réutilisation de leurs travaux, en convenant des formats de sortie, en documentant le code sous-jacent aux analyses et en fournissant des outils pour intégrer les modèles. À cette fin, les outils open-source scriptables sont extrêmement utiles. Cette thèse tente de faire un pas en avant dans cette direction

Asmase Regulates autophagy and lysosomal membrane permeabilization and its inhibition prevents early stage nonalcoholic steatohepatitis

Background & Aims: Acid sphingomyelinase (ASMase) is activated in nonalcoholic steatohepatitis (NASH). However, ASMase's contribution to NASH is poorly understood and limited to hepatic steatosis and glucose metabolism. Here we examined ASMase's role in high fat diet (HFD)-induced NASH. Methods: Autophagy, endoplasmic reticulum (ER) stress and lysosomal membrane permeabilization (LMP) were determined in ASMase-/- mice fed HFD. The impact of pharmacological ASMase inhibition on NASH was analyzed in wild type mice fed HFD. Results: ASMase deficiency determined resistance to HFD or methionine and choline deficient diet-mediated hepatic steatosis. ASMase-/- mice were resistant to HFD-induced hepatic ER stress, but sensitive to tunicamycin-mediated ER stress and steatosis, indicating selectivity in the resistance of ASMase-/- mice to ER stress. Autophagic flux determined in the presence of rapamycin and/or chloroquine was lower in primary mouse hepatocytes (PMH) from ASMase-/- mice and accompanied by increased p62 levels, suggesting autophagic impairment. Moreover, autophagy suppression by chloroquine and brefeldinA caused ER stress in PMH from ASMase+/+ mice but not ASMase-/- mice. ASMase-/- PMH exhibited increased lysosomal cholesterol loading, decreased LMP and apoptosis resistance induced by O-methyl-serine dodecylamide hydrochloride or palmitic acid, effects that were reversed by decreasing cholesterol levels by the oxysterol 25-hydroxycholesterol. In vivo pharmacological ASMase inhibition by amitriptyline, a widely used tricyclic antidepressant, protected wild type mice against HFD- induced hepatic steatosis, fibrosis, and liver damage, effects indicative of early-stage NASH. Conclusions: These findings underscore a critical role for ASMase in diet-induced NASH and suggest the potential of amitriptyline as a treatment for patients with NASH

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Frequency of BRAF V600E Mutation in the Mexican Population of Patients With Metastatic Melanoma

Purpose: The BRAF V600E mutation has been described in melanomas occurring in the Caucasian, European, and Asian populations. However, in the Mexican population, the status and clinical significance of BRAF mutation has not been researched on a large scale. Methods: Consecutive BRAF-tested Mexican patients with metastatic melanoma (n = 127) were analyzed for mutations in exon 15 of the BRAF gene in genomic DNA by real-time polymerase chain reaction technology for amplification and detection. The results were correlated with the clinical-pathologic features and the prognosis of the patients. Results: The frequency of somatic mutation V600E within the BRAF gene was 54.6% (43 of 127 patients). Nodular melanoma was the most prevalent subtype in our population, with BRAF mutations in 37.2% (16 of 55 patients). In contrast, superficial spread had a frequency of 18.6% BRAF mutation (eight of 24). Other clinicopathologic features were assessed to correlate with the mutation status. Conclusion: This study searched for the most prevalent BRAF V600E mutation type in melanoma in a heterogeneous population from Mexico. Nodular melanoma was found to be the most prevalent in metastatic presentation and the presence of BRAF V600E mutation, perhaps related to the mixed ancestry; in the north, ancestry is predominantly European and in the south, it is predominantly Asian. The outcomes of the mutation correlations were similar to those found in other populations

Diagnostico y tratamiento de la myasthenia gravis estudio de una poblacion hospitalaria

Durante la observacion de 50 pacientes con Myasthenia gravis entre los anos 1974 y 1987 se encontro un predominio del sexo femenino en la proporcion de 2,5 a 1 y mayor frecuencia de presentacion en Ias 3ª y 5ª décadas de la vida. Luego de la evaluacion clínica, el diagnóstico fué confirmado mediante: (1) prueba dei edrofonio, (2) estímulo nervioso repetitivo, (3) dosaje de anticuerpos antirreceptor colinérgico y (4) transferencia pasiva del suero al raton con ulterior niedicion de la amplitud de mepp's. La positividad diagnostica vario entre el 90 y el 100%, segun el tipo de prueba empleada. El estúdio radiológico del timo fué hecho con neumomediastinografía. obteniendose excelente correlación con la descripcion histológica de la glândula, y con tomografia computada, que demostro menor eficiência diagnostica. El tratamiento fué implementado en base a anticolinesterásicos, timectomía y corticoterapia inmunosupresora, evidenciandose con esta última mejores resultados. Nueve pacientes desarrollaron peoria transitória del cuadro muscular al iniciarse el tratamiento esteroideo, 6 de ellos exhibieron posteriormente evolucion desfavorable. Esta observacion aparenta tener valor pronóstico en la evolucion de la MG

Outcomes in Newly Diagnosed Atrial Fibrillation and History of Acute Coronary Syndromes: Insights from GARFIELD-AF

BACKGROUND: Many patients with atrial fibrillation have concomitant coronary artery disease with or without acute coronary syndromes and are in need of additional antithrombotic therapy. There are few data on the long-term clinical outcome of atrial fibrillation patients with a history of acute coronary syndrome. This is a 2-year study of atrial fibrillation patients with or without a history of acute coronary syndromes