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- Mewton, Nathan, et al.
(författare)
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Rationale and design of the Cyclosporine to ImpRove Clinical oUtcome in ST-elevation myocardial infarction patients (the CIRCUS trial)
- 2015
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Ingår i: American Heart Journal. - : Elsevier BV. - 1097-6744 .- 0002-8703. ; 169:6, s. 6-766
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Tidskriftsartikel (refereegranskat)abstract
- Background Both acute myocardial ischemia and reperfusion contribute to cardiomyocyte death in ST-elevation myocardial infarction (STEMI). The final infarct size is the principal determinant of subsequent clinical outcome in STEMI patients. In a proof-of-concept phase II trial, the administration of cyclosporine prior to primary percutaneous coronary intervention (PPCI) has been associated with a reduction of infarct size in STEMI patients. Methods CIRCUS is an international, prospective, multicenter, randomized, double-blinded, placebo-controlled trial. The study is designed to compare the efficacy and safety of cyclosporine versus placebo, in addition to revascularization by PPCI, in patients presenting with acute anterior myocardial infarction within 12 hours of symptoms onset and initial TIMI flow <= 1 in the culprit left anterior descending coronary artery. Patients are randomized in a 1: 1 fashion to 2.5 mg/kg intravenous infusion of cyclosporine or matching placebo performed in theminutes preceding PCI. The primary efficacy end point of CIRCUS is a composite of 1-year all-cause mortality, rehospitalization for heart failure or heart failure worsening during initial hospitalization, and left ventricular adverse remodeling as determined by sequential transthoracic echochardiography. Secondary outcomes will be tested using a hierarchical sequence of left ventricular (LV) ejection fraction and absolute measurements of LV volumes. The composite of death and rehospitalization for heart failure or heart failure worsening during initial hospitalization will be further assessed at three years after the initial infarction. Results Recruitment lasted from April 2011 to February 2014. The CIRCUS trial has recruited 975 patients with acute anterior myocardial infarction. The 12-months results are expected to be available in 2015. Conclusions The CIRCUS trial is testing the hypothesis that cyclosporine in addition to early revascularization with PPCI compared to placebo in patients with acute anterior myocardial infarction reduces the incidence of death, heart failure and adverse LV remodeling at one-year follow-up.
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- Atar, Dan, et al.
(författare)
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Rationale and Design of the 'MITOCARE' Study: A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of TRO40303 for the Reduction of Reperfusion Injury in Patients Undergoing Percutaneous Coronary Intervention for Acute Myocardial Infarction
- 2012
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Ingår i: Cardiology. - : S. Karger AG. - 1421-9751 .- 0008-6312. ; 123:4, s. 201-207
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Tidskriftsartikel (refereegranskat)abstract
- Treatment of acute ST-elevation myocardial infarction (STEMI) by reperfusion using percutaneous coronary intervention (PCI) or thrombolysis has provided clinical benefits; however, it also induces considerable cell death. This process is called reperfusion injury. The continuing high rates of mortality and heart failure after acute myocardial infarction (AMI) emphasize the need for improved strategies to limit reperfusion injury and improve clinical outcomes. The objective of this study is to assess safety and efficacy of TRO40303 in limiting reperfusion injury in patients treated for STEMI. TRO40303 targets the mitochondrial permeability transition pore, a promising target for the prevention of reperfusion injury. This multicenter, double-blind study will randomize patients with STEMI to TRO40303 or placebo administered just before balloon inflation or thromboaspiration during PCI. The primary outcome measure will be reduction in infarct size (assessed as plasma creatine kinase and troponin I area under the curve over 3 days). The main secondary endpoint will be infarct size normalized to the myocardium at risk (expressed by the myocardial salvage index assessed by cardiac magnetic resonance). The study is being financed under an EU-FP7 grant and conducted under the auspices of the MITOCARE research consortium, which includes experts from clinical and basic research centers, as well as commercial enterprises, throughout Europe. Results from this study will contribute to a better understanding of the complex pathophysiology underlying myocardial injury after STEMI. The present paper describes the rationale, design and the methods of the trial. Copyright (c) 2012 S. Karger AG, Basel
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| 4. |
- Car, Clement, et al.
(författare)
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Population transcriptogenomics highlights impaired metabolism and small population sizes in tree frogs living in the Chernobyl Exclusion Zone
- 2023
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Ingår i: BMC Biology. - : BioMed Central (BMC). - 1741-7007. ; 21
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Tidskriftsartikel (refereegranskat)abstract
- Background: Individual functional modifications shape the ability of wildlife populations to cope with anthropogenic environmental changes. But instead of adaptive response, human-altered environments can generate a succession of deleterious functional changes leading to the extinction of the population. To study how persistent anthropogenic changes impacted local species' population status, we characterised population structure, genetic diversity and individual response of gene expression in the tree frog Hyla orientalis along a gradient of radioactive contamination around the Chernobyl nuclear power plant.Results: We detected lower effective population size in populations most exposed to ionizing radiation in the Chernobyl Exclusion Zone that is not compensated by migrations from surrounding areas. We also highlighted a decreased body condition of frogs living in the most contaminated area, a distinctive transcriptomics signature and stop-gained mutations in genes involved in energy metabolism. While the association with dose will remain correlational until further experiments, a body of evidence suggests the direct or indirect involvement of radiation exposure in these changes.Conclusions: Despite ongoing migration and lower total dose rates absorbed than at the time of the accident, our results demonstrate that Hyla orientalis specimens living in the Chernobyl Exclusion Zone are still undergoing deleterious changes, emphasizing the long-term impacts of the nuclear disaster.
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| 5. |
- Engert, Andreas, et al.
(författare)
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The European Hematology Association Roadmap for European Hematology Research : a consensus document
- 2016
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Ingår i: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
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Tidskriftsartikel (refereegranskat)abstract
- The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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| 6. |
- Avery, Helen, et al.
(författare)
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Le modèle suédois : leçons et perspectives
- 2012
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Ingår i: Les alliances éducatives pour lutter contre le décrochage scolaire. - Bern, Berlin, Bruxelles, Frankfurt am Main, New York, Oxford, Wien : Peter Lang Publishing Group. - 9783035201383 - 9783034311823 ; , s. 239-258
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Bokkapitel (refereegranskat)
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| 7. |
- Bevilacqua, Riccardo, 1974-, et al.
(författare)
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Medley spectrometer for light ions in neutron-induced reactions at 175 MeV
- 2011
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 646:1, s. 100-107
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Tidskriftsartikel (refereegranskat)abstract
- We have upgraded the Medley spectrometer to measure neutron-induced double differential cross-sections for light-ion production, with neutron energies up to 175 MeV. Measurements were performed at the quasi-monoenergetic neutron beam line at the The Svedberg Laboratory, in Uppsala (Sweden). Medley is a spectrometer system composed of eight three-element telescope detectors; Delta E-E technique is used for particle identification and total kinetic energy measurement. We have improved particle separation and installed new detectors that fully stop ions with kinetic energy up to 170 MeV. To reduce the contribution of the low energy tail in the quasi-monoenergetic neutron spectrum, we have applied time-of-flight techniques and investigated the results for measurements with 175 MeV neutrons. We have investigated the response function of the CsI(Tl) scintillators and describe a method for efficiency correction. We have studied the signal-to-background ratio of the new configuration of the spectrometer and of the collimation system. A method to obtain absolute cross-section normalization, separating the peak neutrons from the low-energy tail, is proposed. Finally we have characterized the 175 MeV quasi-monoenergetic neutron spectrum with the Medley spectrometer. This upgraded configuration has been used in 2007 and 2009 for light-ion production measurements at 175 MeV from C, Si, O, Fe, Bi and U.
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| 8. |
- Fletcher, Tim D., et al.
(författare)
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SUDS, LID, BMPs, WSUD and more : The evolution and application of terminology surrounding urban drainage
- 2015
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Ingår i: Urban Water Journal. - 1573-062X. ; 12:7, s. 525-542
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Tidskriftsartikel (refereegranskat)abstract
- The management of urban stormwater has become increasingly complex over recent decades. Consequently, terminology describing the principles and practices of urban drainage has become increasingly diverse, increasing the potential for confusion and miscommunication. This paper documents the history, scope, application and underlying principles of terms used in urban drainage and provides recommendations for clear communication of these principles. Terminology evolves locally and thus has an important role in establishing awareness and credibility of new approaches and contains nuanced understandings of the principles that are applied locally to address specific problems. Despite the understandable desire to have a 'uniform set of terminology', such a concept is flawed, ignoring the fact that terms reflect locally shared understanding. The local development of terminology thus has an important role in advancing the profession, but authors should facilitate communication between disciplines and between regions of the world, by being explicit and accurate in their application. © 2014 © The work of Tim D. Fletcher is Crown copyright in the Commonwealth of Australia 2014, University of Melbourne. The work of Danielle Dagenais is Copyright of the Crown in Canada 2014, University of Montreal. The work of William Shuster was authored as part of his official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 USC. 105, no copyright protection is available for such works under US Law. William F. Hunt, Richard Ashley, David Butler, Scott Arthur, Sam Trowsdale, Sylvie Barraud, Annette Semadeni-Davies, Jean-Luc Bertrand-Krajewski, Peter Steen Mikkelsen, Gilles Rivard, Mathias Uhl and Maria Viklander hereby waive their right to assert copyright, but not their right to be named as co-authors in the article.
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