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3. Analysis of Metrological Provision Problems of a Test Stand for Testing Radio-Electronic Products for Resistance to Irradiation with High-Energy Heavy Ions

Author

Butenko, A. V., Syresin, E. M., Tyutyunnikov, S. I., Batyaev, V. F., Kulevoy, T. V., Pavlov, K. V., Rogov, V. I., Titarenko, A. Yu., Titarenko, Yu. E., Berlyand, A. V., Berlyand, V. A., Sobolevskiy, N. M., Bobrovskiy, D. V., Chumakov, A. I., Saburov, V. O., Soloviev, A. N., and Pesic, M. P.

Published
2019
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7. Flexibility as a Service

Author

van der Aalst, W. M. P., Adams, M., ter Hofstede, A. H. M., Pesic, M., Schonenberg, H., Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Nierstrasz, Oscar, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Sudan, Madhu, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Vardi, Moshe Y., Series editor, Weikum, Gerhard, Series editor, Chen, Lei, editor, Liu, Chengfei, editor, Liu, Qing, editor, and Deng, Ke, editor

Published
2009
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8. Constraint-Based Workflow Models: Change Made Easy

Author

Pesic, M., Schonenberg, M. H., Sidorova, N., van der Aalst, W. M. P., Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Doug, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Meersman, Robert, editor, and Tari, Zahir, editor

Published
2007
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10. DecSerFlow: Towards a Truly Declarative Service Flow Language

Author

van der Aalst, W. M. P., Pesic, M., Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Dough, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Bravetti, Mario, editor, Núñez, Manuel, editor, and Zavattaro, Gianluigi, editor

Published
2006
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11. A Declarative Approach for Flexible Business Processes Management

Author

Pesic, M., van der Aalst, W. M. P., Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Dough, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Eder, Johann, editor, and Dustdar, Schahram, editor

Published
2006
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21. Photochemical regeneration of flavoenzymes – An Old Yellow Enzyme case-study

Author

Rauch, M.C.R. (author), Huijbers, M.M.E. (author), Pabst, M. (author), Paul, C.E. (author), Pesic, M. (author), Arends, I.W.C.E. (author), Hollmann, F. (author), Rauch, M.C.R. (author), Huijbers, M.M.E. (author), Pabst, M. (author), Paul, C.E. (author), Pesic, M. (author), Arends, I.W.C.E. (author), and Hollmann, F. (author)

Abstract

Direct, NAD(P)H-independent regeneration of Old Yellow Enzymes represents an interesting approach for simplified reaction schemes for the stereoselective reduction of conjugated C=C-double bonds. Simply by illuminating the reaction mixtures with blue light in the presence of sacrificial electron donors enables to circumvent the costly and unstable nicotinamide cofactors and a corresponding regeneration system. In the present study, we characterise the parameters determining the efficiency of this approach and outline the current limitations. Particularly, the photolability of the flavin photocatalyst and the (flavin-containing) biocatalyst represent the major limitation en route to preparative application., BT/Biocatalysis, OLD BT/Cell Systems Engineering

Published
2020
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23. Flexibility as a Service

Author

van der Aalst, W. M. P., primary, Adams, M., additional, ter Hofstede, A. H. M., additional, Pesic, M., additional, and Schonenberg, H., additional

Published
2009
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27. Maintaining hepatic PD-L1 expression improves sepsis survival in a murine polymicrobial sepsis model by tolerizing CTL

Author

Knethen, A. von, Schäfer, A., Kuchler, L., Knape, T., Christen, U., Hintermann, E., Fisslthaler, B., Schröder, K., Brandes, R.P., Genz, B., Abshagen, K., Pützer, B.M., Sha, L.K., Weigert, A., Syed, S.N., Schulz, M., Shah, A.M., Ernst, A., Putyrski, M., Finkelmeier, F., Pesic, M., Greten, F., Hoghardt, M., Kempf, V.A.J., Gunne, S., Parnham, M.J., Brüne, B., and Publica

Published
2019

28. Oral Semaglutide Versus Empagliflozin in Patients With Type 2 Diabetes Uncontrolled on Metformin: The PIONEER 2 Trial

Author

Rodbard, HW, Rosenstock, J, Canani, LH, Deerochanawong, C, Gumprecht, J5, Lindberg, SØ, Lingvay, I, Søndergaard, AL, Treppendahl, MB, Montanya, E, Cruz, P, Loredo, L, Luquez, C, Moisello, M, Augusto, GA, Castro, M, Canani, L, Akrap, Branko, Bulum, Tomislav, Rahelić, Dario, Šunić-Grčić, Ivana, Tušek, Srećko, Avramidis, I, Benroubi, M, Didangelos, T, Karousos, G, Pagkalos, E, Sampanis, C, Somali, M, Domboróczki, Z, Faludi, P, Gaál, Z, Kis- Gombos, P, Kocsis, G, Marton, Z, Sudár, Z, Buscemi, S, Di Carlo, A, Dotta, F, Gambineri, A, Lauro, D, Maranghi, M, Arciszewska, M, Gumprecht, J, Matuszewska, K, Skokowska, E, Stasinska, T, Feofanova, S, Filippova, E, Galstyan, G, Gaysina, L, Kunitsyna, M, Suplotova, L, Antic, S, Djukic, A, Mitrovic, M, Pesic, M, Stokic, E, Jodar, E, Martínez, E, Raya, PM, Portillo, CM, Vera, MP, Fernández, MR, San Jose, P, Riera, MT, Boonyavarakul, A, Sriwijitkamol, A, Ajani, D, Armas, E, Barbel- Johnson, K, Bartilucci, D, Bonabi, G, Busch, R, Butuk, D, Cannon, K, Chase, C, Chaykin, L, Cheekati, V, Davis, T, Delgado, B, Farris, N, Graves, M, Ha, C, Harper, L, Herring, S, Hewitt, M, Hsia, D, Jackson, R, Jardula, M, Joyce, M, Juarez, M, Kapoor, A, Karounos, D, Kayne, D, Lacour, A, Ledesma, G, Lipetz, R, Lomboy, J, Lynd, S, Morawski, E, Morin, R, Murphy, R, Overcash, JS, Pullman, J, Ruoff, G, Steenkamp, D, Toro, H, Trachtenbarg, D, Tulloch, B, Weisbrot, A, Wright, A., Rodbard H.W., Rosenstock J., Canani L.H., Deerochanawong C., Gumprecht J., Lindberg S.O., Lingvay I., Sondergaard A.L., Treppendahl M.B., Montanya E., and Buscemi S.

Subjects
Male, Settore MED/09 - Medicina Interna, Endocrinology, Diabetes and Metabolism, Glucagon-Like Peptides, Administration, Oral, Type 2 diabetes, law.invention, Settore MED/13 - Endocrinologia, 0302 clinical medicine, Glucosides, Randomized controlled trial, law, 030212 general & internal medicine, Settore MED/49 - Scienze Tecniche Dietetiche Applicate, Benzhydryl Compound, Middle Aged, Metformin, Treatment Outcome, diabetes mellitus, Drug Therapy, Combination, Female, medicine.drug, Human, Adult, medicine.medical_specialty, Glucagon-Like Peptide, Glucoside, Urology, 030209 endocrinology & metabolism, 03 medical and health sciences, Pharmacotherapy, Double-Blind Method, Weight Loss, Diabetes mellitus, Internal Medicine, medicine, Empagliflozin, Humans, Hypoglycemic Agents, Benzhydryl Compounds, Glycated Hemoglobin, Advanced and Specialized Nursing, Hypoglycemic Agent, business.industry, Semaglutide, medicine.disease, Discontinuation, Diabetes Mellitus, Type 2, business
Abstract

OBJECTIVE Efficacy and safety of the glucagon-like peptide 1 (GLP-1) analog oral semaglutide and the sodium–glucose cotransporter 2 inhibitor empagliflozin were compared in patients with type 2 diabetes uncontrolled on metformin. RESEARCH DESIGN AND METHODS Patients were randomized to once-daily open-label treatment with oral semaglutide 14 mg (n = 412) or empagliflozin 25 mg (n = 410) in a 52-week trial. Key end points were change from baseline to week 26 in HbA1c (primary) and body weight (confirmatory secondary). Two estimands addressed efficacy-related questions: treatment policy (regardless of trial product discontinuation or rescue medication) and trial product (on trial product without rescue medication) in all randomized patients. RESULTS Four hundred (97.1%) patients in the oral semaglutide group and 387 (94.4%) in the empagliflozin group completed the trial. Oral semaglutide provided superior reductions in HbA1c versus empagliflozin at week 26 (treatment policy –1.3% vs. –0.9% [–14 vs. –9 mmol/mol], estimated treatment difference [ETD] –0.4% [95% CI –0.6, –0.3] [–5 mmol/mol (–6, –3)]; P < 0.0001). The treatment difference in HbA1c significantly favored oral semaglutide at week 26 for the trial product estimand (–1.4% vs. –0.9% [–15 vs. –9 mmol/mol], ETD –0.5% [95% CI –0.7, –0.4] [–6 mmol/mol (–7, –5)]; P < 0.0001) and at week 52 for both estimands (P < 0.0001). Superior weight loss was not confirmed at week 26 (treatment policy), but oral semaglutide was significantly better than empagliflozin at week 52 (trial product −4.7 vs. −3.8 kg; P = 0.0114). Gastrointestinal adverse events were more common with oral semaglutide. CONCLUSIONS Oral semaglutide was superior to empagliflozin in reducing HbA1c but not body weight at 26 weeks in patients with type 2 diabetes uncontrolled on metformin. At week 52, HbA1c and body weight (trial product estimand) were significantly reduced versus empagliflozin. Oral semaglutide was well tolerated within the established safety profile of GLP-1 receptor agonists.

Published
2019

29. Expanding the Spectrum of Light-Driven Peroxygenase Reactions

Author

Willot, S.J. (author), Fernandez Fueyo, E. (author), Tieves, F. (author), Pesic, M. (author), Alcalde, Miguel (author), Arends, I.W.C.E. (author), Park, Chan Beum (author), Hollmann, F. (author), Willot, S.J. (author), Fernandez Fueyo, E. (author), Tieves, F. (author), Pesic, M. (author), Alcalde, Miguel (author), Arends, I.W.C.E. (author), Park, Chan Beum (author), and Hollmann, F. (author)

Abstract

Peroxygenases require a controlled supply of H2O2 to operate efficiently. Here, we propose a photocatalytic system for the reductive activation of ambient O2 to produce H2O2 which uses the energy provided by visible light more efficiently based on the combination of wavelength-complementary photosensitizers. This approach was coupled to an enzymatic system to make formate available as a sacrificial electron donor. The scope and current limitations of this approach are reported and discussed., BT/Biocatalysis, BN/Greg Bokinsky Lab

Published
2019
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30. A new method for measurement of safety rod drop times

Author

Pesic, M., Marinkovic, P., and Stefanovic, D.

Subjects
Transducers -- Innovations, Analog to digital converters -- Research, Nuclear reactors -- Safety and security measures, Business, Electronics, Electronics and electrical industries
Abstract

A new method for the accurate measurement of safety rod drop times is proposed. It is based on a fast electromagnetic transducer and an analog-to-digital converter (ADC) connected to a computer system. Evaluation of recorded data is conducted by a developed computer codes. The first measurements performed at the HERBE fast-thermal RB reactor show that a relative uncertainty (confidence level 95%) of less than 6% can be achieved in determination of rod drop time (with time intervals ranging from 0.4-10.0 s). Further improvements in accuracy are possible.

Published
1992

33. Combining Photo-Organo Redox- and Enzyme Catalysis Facilitates Asymmetric C-H Bond Functionalization

Author

Zhang, W. (author), Fernandez Fueyo, E. (author), Hollmann, F. (author), Leemans Martin, L. (author), Pesic, M. (author), Wardenga, Rainer (author), Höhne, Matthias (author), Schmidt, S. (author), Zhang, W. (author), Fernandez Fueyo, E. (author), Hollmann, F. (author), Leemans Martin, L. (author), Pesic, M. (author), Wardenga, Rainer (author), Höhne, Matthias (author), and Schmidt, S. (author)

Abstract

In this study, we combined photo-organo redox catalysis and biocatalysis to achieve asymmetric C–H bond functionalization of simple alkane starting materials. The photo-organo catalyst anthraquinone sulfate (SAS) was employed to oxyfunctionalise alkanes to aldehydes and ketones. We coupled this light-driven reaction with asymmetric enzymatic functionalisations to yield chiral hydroxynitriles, amines, acyloins and α-chiral ketones with up to 99 % ee. In addition, we demonstrate functional group interconversion to alcohols, esters and carboxylic acids. The transformations can be performed as concurrent tandem reactions. We identified the degradation of substrates and inhibition of the biocatalysts as limiting factors affecting compatibility, due to reactive oxygen species generated in the photocatalytic step. These incompatibilities were addressed by reaction engineering, such as applying a two-phase system or temporal and spatial separation of the catalysts. Using a selection of eleven starting alkanes, one photo-organo catalyst and 8 diverse biocatalysts, we synthesized 26 products and report for the model compounds benzoin and mandelonitrile > 97 % ee at gram scale., BT/Biocatalysis, BN/Greg Bokinsky Lab

Published
2018
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34. Biocatalytic Oxidation Reactions: A Chemist's Perspective

Author

Dong, J. (author), Fernandez Fueyo, E. (author), Hollmann, F. (author), Paul, C.E. (author), Pesic, M. (author), Schmidt, S. (author), Wang, Yonghua (author), Younes, S.H.H. (author), Zhang, W. (author), Dong, J. (author), Fernandez Fueyo, E. (author), Hollmann, F. (author), Paul, C.E. (author), Pesic, M. (author), Schmidt, S. (author), Wang, Yonghua (author), Younes, S.H.H. (author), and Zhang, W. (author)

Abstract

Oxidation chemistry using enzymes is approaching maturity and practical applicability in organic synthesis. Oxidoreductases (enzymes catalysing redox reactions) enable chemists to perform highly selective and efficient transformations ranging from simple alcohol oxidations to stereoselective halogenations of non‐activated C−H bonds. For many of these reactions, no “classical” chemical counterpart is known. Hence oxidoreductases open up shorter synthesis routes based on a more direct access to the target products. The generally very mild reaction conditions may also reduce the environmental impact of biocatalytic reactions compared to classical counterparts. In this Review, we critically summarise the most important recent developments in the field of biocatalytic oxidation chemistry and identify the most pressing bottlenecks as well as promising solutions., BT/Biocatalysis, BN/Greg Bokinsky Lab

Published
2018
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35. Multienzymatic in situ hydrogen peroxide generation cascade for peroxygenase-catalysed oxyfunctionalisation reactions

Author

Pesic, M. (author), Willot, S.J. (author), Fernandez Fueyo, E. (author), Tieves, F. (author), Alcalde, Miguel (author), Hollmann, F. (author), Pesic, M. (author), Willot, S.J. (author), Fernandez Fueyo, E. (author), Tieves, F. (author), Alcalde, Miguel (author), and Hollmann, F. (author)

Abstract

There is an increasing interest in the application of peroxygenases in biocatalysis, because of their ability to catalyse the oxyfunctionalisation reaction in a stereoselective fashion and with high catalytic efficiencies, while using hydrogen peroxide or organic peroxides as oxidant. However, enzymes belonging to this class exhibit a very low stability in the presence of peroxides. With the aim of bypassing this fast and irreversible inactivation, we study the use of a gradual supply of hydrogen peroxide to maintain its concentration at stoichiometric levels. In this contribution, we report a multienzymatic cascade for in situ generation of hydrogen peroxide. In the first step, in the presence of NAD+ cofactor, formate dehydrogenase from Candida boidinii (FDH) catalysed the oxidation of formate yielding CO2. Reduced NADH was reoxidised by the reduction of the flavin mononucleotide cofactor bound to an old yellow enzyme homologue from Bacillus subtilis (YqjM), which subsequently reacts with molecular oxygen yielding hydrogen peroxide. Finally, this system was coupled to the hydroxylation of ethylbenzene reaction catalysed by an evolved peroxygenase from Agrocybe aegerita (rAaeUPO). Additionally, we studied the influence of different reaction parameters on the performance of the cascade with the aim of improving the turnover of the hydroxylation reaction., Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public., BT/Biocatalysis, BN/Greg Bokinsky Lab

Published
2018
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36. A Photoenzymatic NADH Regeneration System

Author

Höfler, G.T. (author), Fernandez Fueyo, E. (author), Pesic, M. (author), Younes, S.H.H. (author), Choi, Eun Gyu (author), Kim, Yong H. (author), Urlacher, Vlada B. (author), Arends, I.W.C.E. (author), Hollmann, F. (author), Höfler, G.T. (author), Fernandez Fueyo, E. (author), Pesic, M. (author), Younes, S.H.H. (author), Choi, Eun Gyu (author), Kim, Yong H. (author), Urlacher, Vlada B. (author), Arends, I.W.C.E. (author), and Hollmann, F. (author)

Abstract

A photoenzymatic NADH regeneration system was established. The combination of deazariboflavin as a photocatalyst with putidaredoxin reductase enabled the selective reduction of NAD+ into the enzyme-active 1,4-NADH to promote an alcohol dehydrogenase catalysed stereospecific reduction reaction. The catalytic turnover of all the reaction components was demonstrated. Factors influencing the efficiency of the overall system were identified., BT/Biocatalysis, BN/Greg Bokinsky Lab, BT/Biotechnology

Published
2018
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37. Deazaflavins as photocatalysts for the direct reductive regeneration of flavoenzymes

Author

van Schie, M.M.C.H. (author), Younes, S.H.H. (author), Rauch, M.C.R. (author), Pesic, M. (author), Paul, C.E. (author), Arends, I.W.C.E. (author), Hollmann, F. (author), van Schie, M.M.C.H. (author), Younes, S.H.H. (author), Rauch, M.C.R. (author), Pesic, M. (author), Paul, C.E. (author), Arends, I.W.C.E. (author), and Hollmann, F. (author)

Abstract

Deazaflavins are potentially useful redox mediators for the direct, nicotinamide-independent regeneration of oxidoreductases. Especially the O2-stability of their reduced forms have attracted significant interest for the regeneration of monooxygenases. In this contribution we further investigate the photochemical properties of deazaflavins and investigate the scope and limitations of deazaflavin-based photoenzymatic reaction systems., Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public., BT/Biocatalysis, BT/Biotechnology

Published
2018
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38. Carbon Nanotube-Graphitic Carbon Nitride Hybrid Films for Flavoenzyme-Catalyzed Photoelectrochemical Cells

Author

Son, Eun Jin (author), Lee, Sahng Ha (author), Kuk, Su Keun (author), Pesic, M. (author), Choi, Da Som (author), Ko, Jong Wan (author), Kim, Kayoung (author), Hollmann, F. (author), Park, Chan Beum (author), Son, Eun Jin (author), Lee, Sahng Ha (author), Kuk, Su Keun (author), Pesic, M. (author), Choi, Da Som (author), Ko, Jong Wan (author), Kim, Kayoung (author), Hollmann, F. (author), and Park, Chan Beum (author)

Abstract

In green plants, solar-powered electrons are transferred through sophistically arranged photosystems and are subsequently channelled into the Calvin cycle to generate chemical energy. Inspired by the natural photosynthetic scheme, a photoelectrochemical cell (PEC) is constructed configured with protonated graphitic carbon nitride (p-g-C3N4) and carbon nanotube hybrid (CNT/p-g-C3N4) film cathode, and FeOOH-deposited bismuth vanadate (FeOOH/BiVO4) photoanode for the production of industrially useful chiral alkanes using an old yellow enzyme homologue from Thermus scotoductus (TsOYE). In the biocatalytic PEC platform, photoexcited electrons provided by the FeOOH/BiVO4 photoanode are transferred to the robust and self-standing CNT/p-g-C3N4 hybrid film that electrocatalytically reduces flavin mononucleotide (FMN) mediator. The p-g-C3N4 promotes a two-electron reduction of FMN coupled with an accelerated electron transfer by the conductive CNT network. The reduced FMN subsequently delivers the electrons to TsOYE for the highly enantioselective conversion of ketoisophorone to (R)-levodione. Under light illumination (>420 nm) and external bias, (R)-levodione is synthesized with the enantiomeric excess value of above 83%, not influenced by the scale of applied bias, simultaneously exhibiting stable and high current efficiency. The results suggest that the biocatalytic PEC made up of economical materials can selectively synthesize high-value organic chemicals using water as an electron donor., Accepted Author Manuscript, BT/Biocatalysis

Published
2017
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39. Characterization of the Old Yellow Enzyme Homolog from Bacillus subtilis (YqjM)

Author

Pesic, M. (author), Fernandez Fueyo, E. (author), Hollmann, F. (author), Pesic, M. (author), Fernandez Fueyo, E. (author), and Hollmann, F. (author)

Abstract

Old Yellow Enzymes (OYEs) have become practical catalysts for the stereoselective trans-hydrogenation of conjugated C=C-double bonds. Despite their importance, in-depth characterization of their kinetic parameters and factors influencing their activity and stability have largely been neglected in the past years. In this study, we close this gap for one of the most prominent OYEs, i. e. the OYE from Bacillus subtilis (YqjM)., BT/Biocatalysis

Published
2017
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40. Cofactor-Free, Direct Photoactivation of Enoate Reductases for the Asymmetric Reduction of C=C Bonds

Author

Lee, Sahng Ha (author), Choi, Da Som (author), Pesic, M. (author), Lee, Yang Woo (author), Paul, C.E. (author), Hollmann, F. (author), Park, Chan Beum (author), Lee, Sahng Ha (author), Choi, Da Som (author), Pesic, M. (author), Lee, Yang Woo (author), Paul, C.E. (author), Hollmann, F. (author), and Park, Chan Beum (author)

Abstract

Enoate reductases from the family of old yellow enzymes (OYEs) can catalyze stereoselective trans-hydrogenation of activated C=C bonds. Their application is limited by the necessity for a continuous supply of redox equivalents such as nicotinamide cofactors [NAD(P)H]. Visible light-driven activation of OYEs through NAD(P)H-free, direct transfer of photoexcited electrons from xanthene dyes to the prosthetic flavin moiety is reported. Spectroscopic and electrochemical analyses verified spontaneous association of rose bengal and its derivatives with OYEs. Illumination of a white light-emitting-diode triggered photoreduction of OYEs by xanthene dyes, which facilitated the enantioselective reduction of C=C bonds in the absence of NADH. The photoenzymatic conversion of 2-methylcyclohexenone resulted in enantiopure (ee>99 %) (R)-2-methylcyclohexanone with conversion yields as high as 80–90 %. The turnover frequency was significantly affected by the substitution of halogen atoms in xanthene dyes., BT/Biocatalysis

Published
2017
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42. Declarative and procedural approaches for modelling clinical guidelines: Addressing flexibility issues

Author

Mulyar, N.A., Pesic, M., Aalst, van der, W.M.P., Peleg, M., Hofstede, ter, A.H.M., Benatallah, B., Paik, H.Y., Information Systems IE&IS, and Information Systems W&I

Subjects
Flexibility (engineering), Management science, Computer science, business.industry, Encoding (memory), Temporal logic, Guideline, State (computer science), Software engineering, business, Domain (software engineering)
Abstract

Recent analysis of clinical Computer-Interpretable Guideline (CIG) modelling languages from the perspective of the control-flow patterns has revealed limited capabilities of these languages to provide flexibility for encoding and executing clinical guidelines. The concept of flexibility is of major importance in the medical-care domain since no guarantee can be given on predicting the state of patients at the point of care. In this paper, we illustrate how the flexibility of CIG modelling languages can be improved by describing clinical guidelines using a declarative approach. We propose a CIGDec language for modelling and enacting clinical guidelines.

Published
2008

48. Impact of field cycling on HfO2 based non-volatile memory devices

Author

Schroeder, U., primary, Pesic, M., additional, Schenk, T., additional, Mulaosmanovic, H., additional, Slesazeck, S., additional, Ocker, J., additional, Richter, C., additional, Yurchuk, E., additional, Khullar, K., additional, Muller, J., additional, Polakowski, P., additional, Grimley, E. D., additional, LeBeau, J. M., additional, Flachowsky, S., additional, Jansen, S., additional, Kolodinski, S., additional, van Bentum, R., additional, Kersch, A., additional, Kunneth, C., additional, and Mikolajick, T., additional

Published
2016
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50. Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo

Author

UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, Bentley-Lewis, R., Aguilar, D., Riddle, M.C., Claggett, B., Diaz, R., Dickstein, K., Gerstein, H.C., Johnston, P., Køber, L.V., Lawson, F., Lewis, E.F., Maggioni, A.P., McMurray, J.J.V., Ping, L., Probstfield, J.L., Solomon, S.D., Tardif, J.-C., Wu, Y., Pfeffer, M.A., Barkoudah, E., Brahimi, A., Charytan, D., Finn, P., Flynn, A., Hartley, L.H., Henderson, G., Joseph, J., Odutayo, K., Rajesh, V., Vazir, A., Weinrauch, L., Del Prato, S., Petrie, J., Kaplan, A., Lieberman, P., Zuraw, B.L., O'Reilly, E., Patel, K., Allen, P., Scarpa, A., Schattner, M., Granger, C., Rouleau, J., DeMets, D., Chaturvedi, N., Raccah, D., Aizenberg, D., Alvarez, C., Alvarisqueta, A., Baccaro, C., Bartolacci, I., Bordonava, A., Bustamante Labarta, M., Caccavo, A., Calella, P., Cantero, M., Codutti, R., Commendatore, V., Costamagna, O., Cuello, J., Fernandez, A., Garcia Duran, R., Gomez Vilamajo, O., Gorban De Lapertosa, S., Grinfeld, D., Hermida, S., Lagrutta, M., Leon De La Fuente, R., Licheri, A., Luciardi, H., Mackinnon, I., Maffei, L., Marino, J., Montaña, O., Novaretto, L., Orio, S., Orlandini, A., Oviedo, A., Pérez Manghi, F., Patocchi, C., Ramos, H., Rolandi, F., Saa Zarandon, R., Saavedra, S.S., Schiavi, L., Schygiel, P., Trivi, M., Ulla, M., Urdiales, P., Vallejos, J., Vico, M., Waisman, F., Amerena, J., Paul, V., Sangla, K., Van Gaal, W., Yeap, B., Fasching, P., Pieber, T., Danilova, L., Mitkovskaya, N., Sudzhaeva, S., Mathieu, C., Pouleur, Anne-Catherine, Botelho, R.V., Cerqueira, M.J., Chacra, A., Dos Santos, F., Feitosa, G., Forti, A., Golbert, M., Halpern, A., Hissa, M., Lisboa, H., Moraes, J., Nery, M., Quadros, A., Raduan, R., Reis, G., Ribeiro Filho, F., Rollin, G., Rossi, P., Santos, E., Sgarbi, J., Souza, J., Souza, M.R., Delchev, A., Ivanov, V., Klyuchkova, N., Kyoleyan, M., Levterov, G., Lucheva, M., Raev, D., Shumkova, R., Tokmakova, M., Tzekova, M., Yordanov, V., Bailey, G., Bertrand, O., Bhargava, R., Burton, J., Campeau, J., Dumas, R., Filteau, P., Syan, G., Syan, R., Tsoukas, G., Warnica, J.W., Acuña, S., Araneda, G., Bunster, L., Cobos, L., Corbalán, R., Dussaillant, G., Eggers, G., Florenzano, F., Godoy, G., Huidobro, L.A., Lahsen, R., Lanas, F., Larenas, G., Manriquez, L., Medina, M., Palma, J.C., Perez, L., Potthoff, S., Raffo, C., Reyes, E., Saavedra, V., Sanhueza, P., Sepulveda, P., Solis, C.L., Soto, N., Torres, C., Westerberg, B., Yañez, M., Chen, L., Dong, Y., Du, J., Guo, X., Han, P., Hu, T., Jiang, B., Ke, Y., Li, Z., Lu, J., Ma, C., Peng, Y., Shi, Y., Su, G., Tang, B., Xu, B., Yang, J., Yang, Y., Accini, J.L., Arteaga, J.M., Botero, R., Castillo, G., Coronel, J., Cure, C., Garcia, H., Garcia, L., Gomez, C., Hernandez Triana, E., Hernandez, H., Lopez, M., Lopez, P., Manzur, F., Molina, D., Rodriguez, J., Sanchez Vallejo, G., Yupanqui, H., Bronnum-Schou, J., Kaiser Nielsen, P., Nielsen, H., Rønne, H., Rasmussen, S., Rungby, J., Skagen, K., Thomsen, K.K., Torp-Pedersen, C., Duarte-Vera, Y., Marmol Alvear, R., Peñaherrera-Patiño, C., Assaad, S., Shelbaya, S., Ambos, A., Jakovlev, U., Lubi, M., Märtsin, K., Rosenthal, S., Vides, H., Alanko, J., Korsoff, P., Koski, A.-M., Lahtela, J., Nelimarkka, L., Tuomilehto, J., Cariou, B., Catargi, B., Ducloux, R., Hadjadj, S., Kerlan, V., Malecot, J.-M., Petit, C., Rodier, M., Chumburidze, V., Glonti, S., Lominadze, Z., Todua, F., Contzen, C., Marck, C., Fischer, H., Hagenow, A., Himpel-Bönninghoff, A., Kihm, L., Killat, H., Kleinertz, K., Kosch, C., Kreutzmann, K., Lappo, M., Mertes, B., Piechatzek, R., Prohaska, M., Rinke, A., Schellenberg, D., Toursarkissian, N., Arango, J., Gonzalez, R., Granados, A., Herrera, M., Montenegro, P., Munoz, R., Rodriguez, E., Turcios, E., Villalobos, R., Wyss, F., Hatterjee, S., Chopda, M., Chopra, V., Deshpande, N., Dutta, R., Dwivedi, S., Gandhi, P., Gupta, S.K., Gupta, J.B., Gupta, S., Hiregouder, N., Jha, S., Joshi, A., Khan, N., Kumbla, M., Magdum, M., Murthy, K., Prabhu, M., Sahay, R., Sethuraman, S., Shah, N., Shamanna, P., Singh, K.S., Singh, P., Somasekharan, A., Sreenivasamurthy, L., Supe, P., Adawi, F., Atar, S., Cohen, O., Efrati, S., Karnieli, E., Klainman, E., Minuchin, O., Mosenzon, O., Stern, N., Turgeman, Y., Wainstein, J., Aimaretti, G., Berra, C., Ciardullo, A.V., Consoli, A., Cucinotta, D., Di Marco, S., Giorda, C., Giordano, C., Mannucci, E., Orsi, E., Piatti, P., Pontiroli, A., Ponzani, P., Pozzilli, P., Rivellese, A., Akahori, H., Eki, Y., Fujii, K., Hata, Y., Himeno, H., Hirayama, A., Kishimoto, I., Kobayashi, Y., Miyaoka, H., Niiya, T., Nishi, Y., Nozaki, A., Nunohiro, T., Saito, T., Satoh, Y., Takahashi, A., Takahashi, J., Takase, H., Takase, S., Tsuboko, Y., Tsujimoto, M., Tsujino, M., Tsuzuki, M., Watanabe, S., Yamada, T., Chung, W.J., Rim, S., Jang, H., Kim, U., Chung, C.H., Shin, S.-H., Kim, K., Kim, J., Rha, S., Lee, N.H., Kim, C.-J., Park, K.S., Amolina, I., Ducena, K., Helda, R., Konrade, I., Pirags, V., Sime, I., Sokolova, J., Kakariekiene, V., Kavaliauskiene, R., Petrulioniene, Z., Sakalyte, G., Urboniene, A., Zarankiene, R., Uribe, M., Garcia-Hernandez, P., Garza, J., Vazquez-Garcia, A., Gonzalez, J.G., Escalante, M., Zavala, A., Bayram, E., Hernandez-Muñuzuri, J., Ramos, Lopez, G.A., Lujan, J., Garcia-Soria, M., Velasco-Sanchez, R., Rodriguez, I., Jimenez, S., Galeana, C., Lara, S., Garcia-Castillo, A., Castro, M.G., Aguilar-Orozco, R., Lopez Rosas, E., Vidrio, M., Llamas, G., Stobschinski De Alba, C.A., Carranza-Madrigal, J., Cardosa-Torres, F., Cornel, J.H., Dekkers, P., Frederiks, J., Hermans, W., Lok, D., Meeder, J., Nierop, P., Cooper, J., Lappegård, K.T., Nedrebø, B.G., Castro, E., Gonzalez Castillo, B., Gonzalez, E., Nieto Ortega, R., Andrade, M., Calderon, J., Chavez, C., Correa Flores, R.M., Farfan, J., Lu, L., Luque, E., Manrique, H., Mogrovejo, W., Pariona-Javier, M., Pinto, M., Roldan, Y., Zubiate, C., Dans, A., Gomez, M.H., Panelo, A., Rey, N., Sulit, D.J., Sy, R.A., Timonera, M., Bednarski, J., Bijata-Bronisz, R., Bryniarski, L., Busz-Papiez, B., Czajkowska-Kaczmarek, E., Drzewiecka, A., Dulak, E., Gorska, M., Hamankiewicz, M., Janik, K., Kincel, K., Konieczny, M., Lubinski, A., Olszanecka-Glinianowicz, M., Ponikowski, P., Pulka, G., Rekosz, J., Skudlarski, D., Szymkowiak, K., Wilczewski, P., Bragança, N., Duarte, J., Monteiro, P., Rodrigues, E., Vinhas, M., Adina, P.-M., Avram, R.I., Cif, A., Creteanu, G., Dragomir, D., Ferariu, I.E., Iancu, A.-C., Istratoaie, O., Ivanica, G., Lichiardopol, R., Militaru, C., Minescu, B., Onaca, A., Pintilei, E., Podoleanu, C., Pop, L., Popa, B., Ranetti, A.E., Rosu, D., Tase, A., Tesloianu, D.N., Vinereanu, D., Ageev, F., Akhmedzhanov, N., Barbarash, O., Barbarich, V., Belousov, Y., Berns, S., Bokarev, I., Bolshakova, O., Boyarkin, M., Chumakova, G., Dmitry, P., Fitilev, S., Galyavich, A., Glezer, M., Ivanova, L., Kalashnikov, V., Kalashnikova, M., Karpov, Y., Khaisheva, L., Khalimov, Y., Kobalava, Z., Kosmachova, E., Kostenko, V., Koziolova, N., Kulibaba, E., Lesnov, V., Libov, I., Lyamina, N., Markov, V., Moiseev, V., Molchanova, O., Oleynikov, V., Orlikova, O., Panov, A., Rafalskiy, V., Rodionova, T., Samitin, V., Schokotov, V., Shilkina, N., Shogenov, Z., Shustov, S., Shvarts, Y., Sobolev, K., Stryuk, R., Suplotova, L., Viktorova, I., Vishnevsky, A., Vorokhobina, N., Yakusevich, V., Yakushin, S., Zadionchenko, V., Zalevskaya, A., Zalevsky, G., Zateyshchikova, A., Andjelic Jelic, M., Kocic, R., Komnenovic, S., Lalic, K., Lalic, N., Micic, D., Otasevic, P., Pesic, M., Seferovic, P., Stankovic, G., Arnold, S., Burgess, L., Coetzee, K., Dawood, S., Delport, E., Ebrahim, I., Ellis, G., Ismail, S., Kelbe, D., Naidoo, V., Ntsekhe, M., Sebastian, P.J., Siebert, M., Van Zyl, L., Venter, T., Lonso, E., Antorrena, I., Bodi, V., Botella, M., De La Fuente, J., Delgado, E., Duran Garcia, S., Elorza, J., Enciso, F., Gaztambide, S., Marin, F., Martin, V., Mauricio, D., Soto, A., Vida, M., Boberg, G., Jörneskog, G., Jendle, J., Mathiesen, U., Svensson, K.-A., Torstensson, I., Vasko, P., Moccetti, T., Chiang, C.-E., Chiu, Y.-W., Huang, T.-Y., Lu, C.-H., Pei, D., Shyu, K.-G., Ueng, K.-C., Wang, T.-D., Abid, M., Ben Abdallah, N., Haouala, H., Slimane, H., Zidi, B., Bascil Tutuncu, N., Camsari, A., Delibasi, T., Dinccag, N., Kultursay, H., Oto, A., Sahin, M., Saygili, F., Yigit, Z., Zorkun, C., Karpenko, O., Korpachev, V., Koval, O., Maslyanko, V., Perepelytsya, M., Pertseva, T., Petrosyan, O., Rudenko, L., Sychov, O., Synenko, V., Tseluyko, V., Zhuravleva, L., Al Mahmeed, W., Kaddaha, G.M., Andrews, R., Bain, S., Basu, A., Bhatnagar, D., Bickerton, A., Browne, D., Gibson, M., Hammond, P., Hanna, F., Issa, B., Jaap, A., Joseph, F., Jude, E., Kelly, C., Khan, A., Malik, R., Mukhopadhyay, B., O'Kane, M., Rayman, G., Robinson, A., Rooney, D., Sainsbury, C., Saravanan, P., Shakher, J., Singh, B., Turner, J., Whitelaw, D., Wilding, J., Wiles, P., Adenuga, B., Ahmad, Z., Akinboboye, O., Akright, L., Alappat, P., Alawad, M., Alfonso, T., Alimard, R., Alzohaili, O., Ariani, M., Arora, C., Azad, N., Azzam, S., Benjamin, S., Block, B., Borzadek, E., Breisblatt, W., Bright, T., Byrd, L., Chiou, C., Chochinov, R., Christensen, T., Christofides, E., Cohen, R., Dawood, G., De Souza, J., Dempsey, M., Eagerton, D., East, C., Elder, C., Fernando, R., Fogelfeld, L., Foucauld, J., French, W., Frohnauer, M., Gaffney, M., Gangopadhyay, S., Gogia, H., Gosmanov, A., Greenberg, C., Greenway, F., Hanna, E., Hargrove, J., Harris, A., Harris, B., Hart, T., Herrington, D., Hewitt, M., Howard, D., Izuora, K., Jetty, P., Kapoor, A., Kasper, J.F., Kelehan, S., Kelly, R., Kereiakes, D., Khaira, A., Khan, M., Khan, S., Korban, E., Kosiborod, M., Laguerre, J., Larocque, J., Latif, K., Lester, F., Levin, P., Levine, S., Li, C., Lovell, C., Lupovitch, S., Madu, I.-J., Mahabadi, V., Mahmood, A., Maragos, S., Mariash, C., Martin, P., Mathew, J., May, M., Mayfield, R., McCall, A., Mcdaniel, C., Mcgrew, F., Mckenzie, M., Mefford, I., Mehta, A., Mikdadi, G., Mikhail, M., Monchamp, T., Moore, C., Moran, M., Morrar, N., Mosley, J., Mulford, M., Murray, J., Nakhle, S., Nallasivan, M., Odio, A., Oh, C., Olelewe, S., Palchick, B., Paliwal, Y., Papademetriou, V., Parikh, N., Patel, S., Phillips, L., Pitts, T., Prieto, F., Puttnam, R., Quyyumi, A., Randhawa, P., Rendell, M., Rhie, F., Roberts, J., Robinson, J., Robinson, M., Rubino, J., Ryan, E., Saathoff, S., Sachmechi, I., Saifi, A., Salacata, A., Sanders, R., Sanson, J., Savin, V., Schabauer, A., Schmedtje, J., Schwartz, A., Scott, C., Selagamsetty, M., Shannon, M., Shaw, S., Singal, D., Sjoberg, R., Smith, K., Sofley, C., Sonn, A., Sorof, S., Soroka, E., Spellman, C.W., Steinhoff, J., Suresh, D., Tahir, M., Tanenberg, R., Thawani, H., Thomson, S., Thrasher, J., Trachtenbarg, D., Trotta, M., Tuan, W., Twahirwa, M., Umpierrez, G., Vaid, B., Vance, C., Wang, T., Warner, A., Watson, H., Weber, S., Webster, B., Weindorff, K., Welch, M., Welker, J., White, A., White, L., Williams, M., Wu, W.-C., Wynne, A., Yocono, M., Yuen, K., UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, Bentley-Lewis, R., Aguilar, D., Riddle, M.C., Claggett, B., Diaz, R., Dickstein, K., Gerstein, H.C., Johnston, P., Køber, L.V., Lawson, F., Lewis, E.F., Maggioni, A.P., McMurray, J.J.V., Ping, L., Probstfield, J.L., Solomon, S.D., Tardif, J.-C., Wu, Y., Pfeffer, M.A., Barkoudah, E., Brahimi, A., Charytan, D., Finn, P., Flynn, A., Hartley, L.H., Henderson, G., Joseph, J., Odutayo, K., Rajesh, V., Vazir, A., Weinrauch, L., Del Prato, S., Petrie, J., Kaplan, A., Lieberman, P., Zuraw, B.L., O'Reilly, E., Patel, K., Allen, P., Scarpa, A., Schattner, M., Granger, C., Rouleau, J., DeMets, D., Chaturvedi, N., Raccah, D., Aizenberg, D., Alvarez, C., Alvarisqueta, A., Baccaro, C., Bartolacci, I., Bordonava, A., Bustamante Labarta, M., Caccavo, A., Calella, P., Cantero, M., Codutti, R., Commendatore, V., Costamagna, O., Cuello, J., Fernandez, A., Garcia Duran, R., Gomez Vilamajo, O., Gorban De Lapertosa, S., Grinfeld, D., Hermida, S., Lagrutta, M., Leon De La Fuente, R., Licheri, A., Luciardi, H., Mackinnon, I., Maffei, L., Marino, J., Montaña, O., Novaretto, L., Orio, S., Orlandini, A., Oviedo, A., Pérez Manghi, F., Patocchi, C., Ramos, H., Rolandi, F., Saa Zarandon, R., Saavedra, S.S., Schiavi, L., Schygiel, P., Trivi, M., Ulla, M., Urdiales, P., Vallejos, J., Vico, M., Waisman, F., Amerena, J., Paul, V., Sangla, K., Van Gaal, W., Yeap, B., Fasching, P., Pieber, T., Danilova, L., Mitkovskaya, N., Sudzhaeva, S., Mathieu, C., Pouleur, Anne-Catherine, Botelho, R.V., Cerqueira, M.J., Chacra, A., Dos Santos, F., Feitosa, G., Forti, A., Golbert, M., Halpern, A., Hissa, M., Lisboa, H., Moraes, J., Nery, M., Quadros, A., Raduan, R., Reis, G., Ribeiro Filho, F., Rollin, G., Rossi, P., Santos, E., Sgarbi, J., Souza, J., Souza, M.R., Delchev, A., Ivanov, V., Klyuchkova, N., Kyoleyan, M., Levterov, G., Lucheva, M., Raev, D., Shumkova, R., Tokmakova, M., Tzekova, M., Yordanov, V., Bailey, G., Bertrand, O., Bhargava, R., Burton, J., Campeau, J., Dumas, R., Filteau, P., Syan, G., Syan, R., Tsoukas, G., Warnica, J.W., Acuña, S., Araneda, G., Bunster, L., Cobos, L., Corbalán, R., Dussaillant, G., Eggers, G., Florenzano, F., Godoy, G., Huidobro, L.A., Lahsen, R., Lanas, F., Larenas, G., Manriquez, L., Medina, M., Palma, J.C., Perez, L., Potthoff, S., Raffo, C., Reyes, E., Saavedra, V., Sanhueza, P., Sepulveda, P., Solis, C.L., Soto, N., Torres, C., Westerberg, B., Yañez, M., Chen, L., Dong, Y., Du, J., Guo, X., Han, P., Hu, T., Jiang, B., Ke, Y., Li, Z., Lu, J., Ma, C., Peng, Y., Shi, Y., Su, G., Tang, B., Xu, B., Yang, J., Yang, Y., Accini, J.L., Arteaga, J.M., Botero, R., Castillo, G., Coronel, J., Cure, C., Garcia, H., Garcia, L., Gomez, C., Hernandez Triana, E., Hernandez, H., Lopez, M., Lopez, P., Manzur, F., Molina, D., Rodriguez, J., Sanchez Vallejo, G., Yupanqui, H., Bronnum-Schou, J., Kaiser Nielsen, P., Nielsen, H., Rønne, H., Rasmussen, S., Rungby, J., Skagen, K., Thomsen, K.K., Torp-Pedersen, C., Duarte-Vera, Y., Marmol Alvear, R., Peñaherrera-Patiño, C., Assaad, S., Shelbaya, S., Ambos, A., Jakovlev, U., Lubi, M., Märtsin, K., Rosenthal, S., Vides, H., Alanko, J., Korsoff, P., Koski, A.-M., Lahtela, J., Nelimarkka, L., Tuomilehto, J., Cariou, B., Catargi, B., Ducloux, R., Hadjadj, S., Kerlan, V., Malecot, J.-M., Petit, C., Rodier, M., Chumburidze, V., Glonti, S., Lominadze, Z., Todua, F., Contzen, C., Marck, C., Fischer, H., Hagenow, A., Himpel-Bönninghoff, A., Kihm, L., Killat, H., Kleinertz, K., Kosch, C., Kreutzmann, K., Lappo, M., Mertes, B., Piechatzek, R., Prohaska, M., Rinke, A., Schellenberg, D., Toursarkissian, N., Arango, J., Gonzalez, R., Granados, A., Herrera, M., Montenegro, P., Munoz, R., Rodriguez, E., Turcios, E., Villalobos, R., Wyss, F., Hatterjee, S., Chopda, M., Chopra, V., Deshpande, N., Dutta, R., Dwivedi, S., Gandhi, P., Gupta, S.K., Gupta, J.B., Gupta, S., Hiregouder, N., Jha, S., Joshi, A., Khan, N., Kumbla, M., Magdum, M., Murthy, K., Prabhu, M., Sahay, R., Sethuraman, S., Shah, N., Shamanna, P., Singh, K.S., Singh, P., Somasekharan, A., Sreenivasamurthy, L., Supe, P., Adawi, F., Atar, S., Cohen, O., Efrati, S., Karnieli, E., Klainman, E., Minuchin, O., Mosenzon, O., Stern, N., Turgeman, Y., Wainstein, J., Aimaretti, G., Berra, C., Ciardullo, A.V., Consoli, A., Cucinotta, D., Di Marco, S., Giorda, C., Giordano, C., Mannucci, E., Orsi, E., Piatti, P., Pontiroli, A., Ponzani, P., Pozzilli, P., Rivellese, A., Akahori, H., Eki, Y., Fujii, K., Hata, Y., Himeno, H., Hirayama, A., Kishimoto, I., Kobayashi, Y., Miyaoka, H., Niiya, T., Nishi, Y., Nozaki, A., Nunohiro, T., Saito, T., Satoh, Y., Takahashi, A., Takahashi, J., Takase, H., Takase, S., Tsuboko, Y., Tsujimoto, M., Tsujino, M., Tsuzuki, M., Watanabe, S., Yamada, T., Chung, W.J., Rim, S., Jang, H., Kim, U., Chung, C.H., Shin, S.-H., Kim, K., Kim, J., Rha, S., Lee, N.H., Kim, C.-J., Park, K.S., Amolina, I., Ducena, K., Helda, R., Konrade, I., Pirags, V., Sime, I., Sokolova, J., Kakariekiene, V., Kavaliauskiene, R., Petrulioniene, Z., Sakalyte, G., Urboniene, A., Zarankiene, R., Uribe, M., Garcia-Hernandez, P., Garza, J., Vazquez-Garcia, A., Gonzalez, J.G., Escalante, M., Zavala, A., Bayram, E., Hernandez-Muñuzuri, J., Ramos, Lopez, G.A., Lujan, J., Garcia-Soria, M., Velasco-Sanchez, R., Rodriguez, I., Jimenez, S., Galeana, C., Lara, S., Garcia-Castillo, A., Castro, M.G., Aguilar-Orozco, R., Lopez Rosas, E., Vidrio, M., Llamas, G., Stobschinski De Alba, C.A., Carranza-Madrigal, J., Cardosa-Torres, F., Cornel, J.H., Dekkers, P., Frederiks, J., Hermans, W., Lok, D., Meeder, J., Nierop, P., Cooper, J., Lappegård, K.T., Nedrebø, B.G., Castro, E., Gonzalez Castillo, B., Gonzalez, E., Nieto Ortega, R., Andrade, M., Calderon, J., Chavez, C., Correa Flores, R.M., Farfan, J., Lu, L., Luque, E., Manrique, H., Mogrovejo, W., Pariona-Javier, M., Pinto, M., Roldan, Y., Zubiate, C., Dans, A., Gomez, M.H., Panelo, A., Rey, N., Sulit, D.J., Sy, R.A., Timonera, M., Bednarski, J., Bijata-Bronisz, R., Bryniarski, L., Busz-Papiez, B., Czajkowska-Kaczmarek, E., Drzewiecka, A., Dulak, E., Gorska, M., Hamankiewicz, M., Janik, K., Kincel, K., Konieczny, M., Lubinski, A., Olszanecka-Glinianowicz, M., Ponikowski, P., Pulka, G., Rekosz, J., Skudlarski, D., Szymkowiak, K., Wilczewski, P., Bragança, N., Duarte, J., Monteiro, P., Rodrigues, E., Vinhas, M., Adina, P.-M., Avram, R.I., Cif, A., Creteanu, G., Dragomir, D., Ferariu, I.E., Iancu, A.-C., Istratoaie, O., Ivanica, G., Lichiardopol, R., Militaru, C., Minescu, B., Onaca, A., Pintilei, E., Podoleanu, C., Pop, L., Popa, B., Ranetti, A.E., Rosu, D., Tase, A., Tesloianu, D.N., Vinereanu, D., Ageev, F., Akhmedzhanov, N., Barbarash, O., Barbarich, V., Belousov, Y., Berns, S., Bokarev, I., Bolshakova, O., Boyarkin, M., Chumakova, G., Dmitry, P., Fitilev, S., Galyavich, A., Glezer, M., Ivanova, L., Kalashnikov, V., Kalashnikova, M., Karpov, Y., 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Abstract

Background: Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Furthermore, patients with T2DM and acute coronary syndrome (ACS) have a particularly high risk of CV events. The glucagonlike peptide 1 receptor agonist, lixisenatide, improves glycemia, but its effects on CV events have not been thoroughly evaluated. Methods: ELIXA (www.clinicaltrials.gov no. NCT01147250) is a randomized, double-blind, placebo-controlled, parallelgroup, multicenter study of lixisenatide in patients with T2DM and a recent ACS event. The primary aim is to evaluate the effects of lixisenatide on CV morbidity and mortality in a population at high CV risk. The primary efficacy end point is a composite of time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Data are systematically collected for safety outcomes, including hypoglycemia, pancreatitis, and malignancy. Results: Enrollment began in July 2010 and ended in August 2013; 6,068 patients from 49 countries were randomized. Of these, 69% are men and 75% are white; at baseline, the mean ± SD age was 60.3 ± 9.7 years, body mass index was 30.2 ± 5.7 kg/m2, and duration of T2DM was 9.3±8.2 years. The qualifying ACS wasamyocardial infarctionin83% and unstableangina in 17%. The study will continue until the positive adjudication of the protocol-specified number of primary CV events. Conclusion: ELIXA will be the first trial to report the safety and efficacy of a glucagon-like peptide 1 receptor agonist in people with T2DM and high CV event risk. © 2015 Elsevier Inc. All rights reserved.

Published
2015

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