Полімер-електролітна мембрана для паливних елементів на основі зшитого полііміду і протонної іонної рідини

The aim of this research was to develop polymer-electrolyte membrane on the base of commercial polyimide Matrimid which has high proton conductivity at elevated temperatures above 100 °C. Hydrophobic ionic liquid 1-butylimidazolium bis(trifluoromethylsulfonyl)imide (BIM-TFSI) has been synthesized and used as proton conducting electrolyte. The electrical conductivity of the ionic liquid determined by electrochemical impedance method was found to have a value of 10–3 S/cm in the temperature range from 100 to 180 °С. The composite film based on Matrimid polyimide containing 70 wt % of protic ionic liquid has been prepared by casting from methylene chloride solution. Polyetheramine Jeffamine® D-2000 was used as a cross-linking agent for polyimide. According to mechanical and thermal analysis data, Matrimid/BIM-TFSI composite has tensile strength of 18 MPa and thermal degradation point of 306 °С. Electrophysical properties of polyimide film impregnated with ionic liquid was studied by two-probe technique at the frequencies of 0.1, 1.0 and 10 kHz by using immitance meter in the temperature range from 25 to 180 °С. The electrical conductivity was found to be 2.7∙10–4 S/cm at room temperature and reached the value of 1.5∙10–3 S/cm at 180 °С. Thus, in this work proton conducting membrane based on commercial polyimide has been obtained for the first time by simple method without additional sulfonation stage. Matrimid/BIM-TFSI composite membrane is promising for applications in fuel cells operating at elevated temperature without external humidification.Целью работы было получение полимер-электролитной мембраны на основе промышленного полиимида Matrimid с высоким уровнем протонной проводимости при температурах выше 100 °С. Синтезирована гидрофобная протонная ионная жидкость бис(трифторметилсульфонил)имид 1-бутилимидазолия (БИМ-ТФСИ), которая была использована в качестве протонпроводящего электролита. Удельная электропроводность ионной жидкости, измеренная методом электрохимического импеданса, имеет значение порядка 10–3 См/см в интервале температур 100–180 °С. Получена композитная пленка на основе полиимида Matrimid, содержащая 70 % ионной жидкости, поливом из раствора в метиленхлориде. Полиэфир Jeffamine® D-2000 использован в качестве сшивающего агента для полиимида. Согласно результатам механических и термических исследований, прочность на разрыв композита Matrimid/БИМ-ТФСИ составляет 18 мПа, а температура начала деструкции – 306 °С. Электрофизические свойства полиимидной пленки, насыщенной протонной ионной жидкостью, исследовали двухконтактным методом с помощью измерителя иммитанса на частотах 0.1, 1.0 и 10 кГц в температурном интервале 25–180 °С. Установлено, что удельная электропроводность материала составляет 2.7∙10–4 См/см при комнатной температуре, возрастая до величины 1.5∙10–3 См/см при 180 °С.  Таким образом, в данной работе впервые получена протонобменная мембрана на основе коммерческого полиимида технологически простым методом, без дополнительной стадии сульфирования полимера. Композитная мембрана Matrimid/БІМ-ТФСІ перспективна для использования в топливных элементах, которые эксплуатируются при температурах выше 100 °С при отсутствии увлажнения.Метою роботи було отримання полімер-електролітної мембрани на основі промислового полііміду Matrimid з високим рівнем протонної провідності при температурі вище 100 °С. Синтезовано гідрофобну іонну рідину біс(трифторметилсульфоніл)імід 1-бутилімідазолію (БІМ-ТФСІ), яку використано в якості протонпровідного електроліту. Питома електропровідність іонної рідини, визначена методом електрохімічного імпедансу, має значення порядку 10-3 См/см в інтервалі температур  100-180 °С. Отримано композитну плівку на основі полііміду Matrimid із вмістом протонної іонної рідини 70 % поливом з розчину в метиленхлориді. Поліетерамін Jeffamine® D-2000 використано в якості зшиваючого агенту для полііміду. Згідно з результатами механічних і термічних досліджень, міцність на розрив композиту Matrimid/БІМ-ЕФСІ становить 18 мПа, а температура початку деструкції – 306 °С. Електрофізичні властивості поліімідної плівки, насиченої протонною іонною рідиною, досліджували двоконтактним методом за допомогою вимірювача іммітансу на частотах 0.1, 1.0 і 10 кГц в температурному інтервалі 25-180 °С. Встановлено, що питома електропровідність матеріалу становить 2.7 ∙ 10-4 См/см при кімнатній температурі, досягаючи величини 1.5 ∙ 10-3 См/см при 180 °С. Таким чином, в даній роботі вперше отримано протонобмінну мембрану на основі комерційного полііміду технологічно простим методом, без додаткової стадії сульфування полімеру. Композитна мембрана Matrimid/БІМ-ТФСІ перспективна для використання в паливних елементах, які експлуатуються при підвищених температурах за відсутності зволоження.

POLYMER-ELECTROLYTE MEMBRANE FOR FUEL CELLS BASED ON CROSS-LINKED POLYIMIDE AND PROTIC IONIC LIQUID

The aim of this research was to develop polymer-electrolyte membrane on the base of commercial polyimide Matrimid which has high proton conductivity at elevated temperatures above 100 °C. Hydrophobic ionic liquid 1-butylimidazolium bis(trifluoromethylsulfonyl)imide (BIM-TFSI) has been synthesized and used as proton conducting electrolyte. The electrical conductivity of the ionic liquid determined by electrochemical impedance method was found to have a value of 10–3 S/cm in the temperature range from 100 to 180 °С. The composite film based on Matrimid polyimide containing 70 wt % of protic ionic liquid has been prepared by casting from methylene chloride solution. Polyetheramine Jeffamine® D-2000 was used as a cross-linking agent for polyimide. According to mechanical and thermal analysis data, Matrimid/BIM-TFSI composite has tensile strength of 18 MPa and thermal degradation point of 306 °С. Electrophysical properties of polyimide film impregnated with ionic liquid was studied by two-probe technique at the frequencies of 0.1, 1.0 and 10 kHz by using immitance meter in the temperature range from 25 to 180 °С. The electrical conductivity was found to be 2.7∙10–4 S/cm at room temperature and reached the value of 1.5∙10–3 S/cm at 180 °С. Thus, in this work proton conducting membrane based on commercial polyimide has been obtained for the first time by simple method without additional sulfonation stage. Matrimid/BIM-TFSI composite membrane is promising for applications in fuel cells operating at elevated temperature without external humidification

2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS)

none107siNon presentemixedValgimigli, Marco*; Bueno, Héctor; Byrne, Robert A.; Collet, Jean-Philippe; Costa, Francesco; Jeppsson, Anders; Kastrati, Adnan; Kolh, Philippe; Mauri, Laura; Montalescot, Gilles; Neumann, Franz-Josef; Petricevic, Mate; Roffi, Marco; Steg, Philippe Gabriel; Zamorano, Jose Luis; Levine, Glenn N.; Badimon, Lina; Vranckx, Pascal; Agewall, Stefan; Andreotti, Felicita; Antman, Elliott; Barbato, Emanuele; Bassand, Jean-Pierre; Bugiardini, Raffaele; Cikirikcioglu, Mustafa; Cuisset, Thomas; De Bonis, Michele; Delgado, Victora; Fitzsimons, Donna; Galiè, Nazzareno; Gilard, Martine; Hamm, Christian W.; Ibanez, Borja; James, Stefan; Knuuti, Juhani; Landmesser, Ulf; Leclercq, Christophe; Lettino, Maddalena; Lip, Gregory; Piepoli, Massimo Francesco; Pierard, Luc; Schwerzmann, Markus; Sechtem, Udo; Simpson, Iain A.; Uva, Miguel Sousa; Stabile, Eugenio; Storey, Robert F.; Tendera, Michal; Van De Werf, Frans; Verheugt, Freek; Aboyans, Victor; Windecker, Stephan; Coca, Antonio; Coman, Ioan Mircea; Dean, Veronica; Delgado, Victoria; Gaemperli, Oliver; Hindricks, Gerhard; Iung, Bernard; Jüni, Peter; Katus, Hugo A.; Lancellotti, Patrizio; McDonagh, Theresa; Ponikowski, Piotr; Richter, DImitrios J.; Shlyakhto, Evgeny; Roithinger, Franz Xaver; Aliyev, Farid; Stelmashok, Valeriy; Desmet, Walter; Postadzhiyan, Arman; Georghiou, Georgios P.; Motovska, Zuzana; Grove, Erik Lerkevang; Marandi, Toomas; Kiviniemi, Tuomas; Kedev, Sasko; Massberg, Steffen; Alexopoulos, DImitrios; Kiss, Robert Gabor; Gudmundsdottir, Ingibjorg Jona; McFadden, Eugène P.; Lev, Eli; De Luca, Leonardo; Sugraliyev, Akhmetzhan; Haliti, Edmond; Mirrakhimov, Erkin; Latkovskis, Gustavs; Petrauskiene, Birute; Huijnen, Steve; Magri, Caroline Jane; Cherradi, Rhizlan; Ten Berg, Jurrien M.; Eritsland, Jan; Budaj, Andrzej; Aguiar, Carlos Tavares; Duplyakov, Dmitry; Zavatta, Marco; Antonijevic, Nebojsa M.; Fras, Zlatko; Montoliu, Antonio Tello; Varenhorst, Christoph; Tsakiris, DImitri; Addad, Faouzi; Aydogdu, Sinan; Parkhomenko, Alexander; Kinnaird, TimValgimigli, Marco*; Bueno, Héctor; Byrne, Robert A.; Collet, Jean-Philippe; Costa, Francesco; Jeppsson, Anders; Kastrati, Adnan; Kolh, Philippe; Mauri, Laura; Montalescot, Gilles; Neumann, Franz-Josef; Petricevic, Mate; Roffi, Marco; Steg, Philippe Gabriel; Zamorano, Jose Luis; Levine, Glenn N.; Badimon, Lina; Vranckx, Pascal; Agewall, Stefan; Andreotti, Felicita; Antman, Elliott; Barbato, Emanuele; Bassand, Jean-Pierre; Bugiardini, Raffaele; Cikirikcioglu, Mustafa; Cuisset, Thomas; De Bonis, Michele; Delgado, Victora; Fitzsimons, Donna; Galiè, Nazzareno; Gilard, Martine; Hamm, Christian W.; Ibanez, Borja; James, Stefan; Knuuti, Juhani; Landmesser, Ulf; Leclercq, Christophe; Lettino, Maddalena; Lip, Gregory; Piepoli, Massimo Francesco; Pierard, Luc; Schwerzmann, Markus; Sechtem, Udo; Simpson, Iain A.; Uva, Miguel Sousa; Stabile, Eugenio; Storey, Robert F.; Tendera, Michal; Van De Werf, Frans; Verheugt, Freek; Aboyans, Victor; Windecker, Stephan; Coca, Antonio; Coman, Ioan Mircea; Dean, Veronica; Delgado, Victoria; Gaemperli, Oliver; Hindricks, Gerhard; Iung, Bernard; Jüni, Peter; Katus, Hugo A.; Lancellotti, Patrizio; McDonagh, Theresa; Ponikowski, Piotr; Richter, DImitrios J.; Shlyakhto, Evgeny; Roithinger, Franz Xaver; Aliyev, Farid; Stelmashok, Valeriy; Desmet, Walter; Postadzhiyan, Arman; Georghiou, Georgios P.; Motovska, Zuzana; Grove, Erik Lerkevang; Marandi, Toomas; Kiviniemi, Tuomas; Kedev, Sasko; Massberg, Steffen; Alexopoulos, DImitrios; Kiss, Robert Gabor; Gudmundsdottir, Ingibjorg Jona; McFadden, Eugène P.; Lev, Eli; De Luca, Leonardo; Sugraliyev, Akhmetzhan; Haliti, Edmond; Mirrakhimov, Erkin; Latkovskis, Gustavs; Petrauskiene, Birute; Huijnen, Steve; Magri, Caroline Jane; Cherradi, Rhizlan; Ten Berg, Jurrien M.; Eritsland, Jan; Budaj, Andrzej; Aguiar, Carlos Tavares; Duplyakov, Dmitry; Zavatta, Marco; Antonijevic, Nebojsa M.; Fras, Zlatko; Montoliu, Antonio Tello; Varenhorst, Christoph; Tsakiris, DImitri; Addad, Faouzi; Aydogdu, Sinan; Parkhomenko, Alexander; Kinnaird, Ti

Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI) : a phase 3, placebo-controlled, randomised trial

Background: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. Methods: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). Findings: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8–3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74–0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, p interaction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78–1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75–1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48–2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36–3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74–1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75–0·95, p=0·005, in contrast to patients without PCI where it did not, p interaction=0·012. Benefit was present irrespective of time from most recent PCI. Interpretation: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk

A Survey of Empirical Results on Program Slicing

International audienceBACKGROUND:Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications.METHODS:This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS:Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043).INTERPRETATION:Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding

Alirocumab and cardiovascular outcomes after acute coronary syndrome

BACKGROUN

Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome

BACKGROUN

Effect of Alirocumab on Mortality After Acute Coronary Syndromes An Analysis of the ODYSSEY OUTCOMES Randomized Clinical Trial

10.1161/CIRCULATIONAHA.118.038840CIRCULATION1402103-11

Apolipoprotein B, Residual Cardiovascular Risk After Acute Coronary Syndrome, and Effects of Alirocumab.

Background: Apolipoprotein B (apoB) provides an integrated measure of atherogenic risk. Whether apoB levels and apoB lowering hold incremental predictive information on residual risk after acute coronary syndrome beyond that provided by low-density lipoprotein cholesterol is uncertain. Methods: The ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) compared the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome and elevated atherogenic lipoproteins despite optimized statin therapy. Primary outcome was major adverse cardiovascular events (MACE; coronary heart disease death, nonfatal myocardial infarction, fatal/nonfatal ischemic stroke, hospitalization for unstable angina). Associations between baseline apoB or apoB at 4 months and MACE were assessed in adjusted Cox proportional hazards and propensity score–matched models. Results: Median follow-up was 2.8 years. In proportional hazards analysis in the placebo group, MACE incidence increased across increasing baseline apoB strata (3.2 [95% CI, 2.9–3.6], 4.0 [95% CI, 3.6–4.5], and 5.5 [95% CI, 5.0–6.1] events per 100 patient-years in strata 35–<50, and ≤35 mg/dL, respectively). Compared with propensity score–matched patients from the placebo group, treatment hazard ratios for alirocumab also decreased monotonically across achieved apoB strata. Achieved apoB was predictive of MACE after adjustment for achieved low-density lipoprotein cholesterol or non–high-density lipoprotein cholesterol but not vice versa. Conclusions: In patients with recent acute coronary syndrome and elevated atherogenic lipoproteins, MACE increased across baseline apoB strata. Alirocumab reduced MACE across all strata of baseline apoB, with larger absolute reductions in patients with higher baseline levels. Lower achieved apoB was associated with lower risk of MACE, even after accounting for achieved low-density lipoprotein cholesterol or non–high-density lipoprotein cholesterol, indicating that apoB provides incremental information. Achievement of apoB levels as low as ≤35 mg/dL may reduce lipoprotein-attributable residual risk after acute coronary syndrome. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01663402.gov; Unique identifier: NCT01663402.URL: https://www