| 21. |
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| 22. |
- De Caterina, Raffaele, et al.
(författare)
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New Oral Anticoagulants in Atrial Fibrillation and Acute Coronary Syndromes : ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease Position Paper
- 2012
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 59:16, s. 1413-1425
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Forskningsöversikt (refereegranskat)abstract
- Until recently, vitamin K antagonists were the only available oral anticoagulants, but with numerous limitations that prompted the introduction of new oral anticoagulants targeting the single coagulation enzymes thrombin (dabigatran) or factor Xa (apixaban, rivaroxaban, and edoxaban) and given in fixed doses without coagulation monitoring. Here we review the pharmacology and the results of clinical trials with these new agents in stroke prevention in atrial fibrillation and secondary prevention after acute coronary syndromes, providing perspectives on their future incorporation into clinical practice. In phase III trials in atrial fibrillation, compared with warfarin, dabigatran etexilate 150 mg B.I.D. reduced the rates of stroke/systemic embolism without any difference in major bleeding; dabigatran etexilate 110 mg B.I.D. had similar efficacy with decreased bleeding; apixaban 5 mg B.I.D. reduced stroke, systemic embolism, and mortality as well as major bleeding; and rivaroxaban 20 mg Q.D. was noninferior to warfarin for stroke and systemic embolism without a difference in major bleeding. All these agents reduced intracranial hemorrhage. Edoxaban is currently being evaluated in a further large phase III trial. Apixaban and rivaroxaban were evaluated in phase III trials for prevention of recurrent ischemia in patients with acute coronary syndromes who were mostly receiving dual antiplatelet therapy, with conflicting results on efficacy but consistent results for increased major bleeding. Overall, the new oral anticoagulants are poised to replace vitamin K antagonists for many patients with atrial fibrillation and may have a role after acute coronary syndromes. Although convenient to administer and manage, they present challenges that need to be addressed.
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| 23. |
- De Caterina, Raffaele, et al.
(författare)
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Oral anticoagulants in coronary heart disease (Section IV) Position paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease
- 2016
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 115:4, s. 685-711
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Tidskriftsartikel (refereegranskat)abstract
- Until recently, vitamin K antagonists (VKAs) were the only available oral anticoagulants evaluated for long-term treatment of patients with coronary heart disease (CHD), particularly after an acute coronary syndrome (ACS). Despite efficacy in this setting, VKAs are rarely used because they are cumbersome to administer. Instead, the more readily manageable antiplatelet agents are the mainstay of prevention in ACS patients. This situation has the potential to change with the introduction of non-VKA oral anticoagulants (NOACs), which are easier to administer than VKAs because they can be given in fixed doses without routine coagulation monitoring. The NOACs include dabigatran, which inhibits thrombin, and apixaban, rivaroxaban and edoxaban, which inhibit factor Xa. Apixaban and rivaroxaban were evaluated in phase III trials for prevention of recurrent ischaemia in ACS patients, most of whom were also receiving dual antiplatelet therapy with aspirin and clopidogrel. Although at the doses tested rivaroxaban was effective and apixaban was not, both agents increased major bleeding. The role for the NOACs in ACS management, although promising, is therefore complicated, because it is uncertain how they compare with newer antiplatelet agents, such as prasugrel, ticagrelor or vorapaxar, and because their safety in combination with these other drugs is unknown. Ongoing studies are also now evaluating the use of NOACs in non-valvular atrial fibrillation patients, where their role is established, with coexistent ACS or coronary stenting. Focusing on CHD, we review the results of clinical trials with the NOACs and provide a perspective on their future incorporation into clinical practice.
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| 24. |
- De Caterina, Raffaele, et al.
(författare)
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Parenteral anticoagulants in heart disease : Current status and perspectives (Section II) Position Paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease
- 2013
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 109:5, s. 769-786
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Tidskriftsartikel (refereegranskat)abstract
- Anticoagulants are a mainstay of cardiovascular therapy, and parenteral anticoagulants have widespread use in cardiology, especially in acute situations. Parenteral anticoagulants include unfractionated heparin, low-molecular-weight heparins, the synthetic pentasaccharides fondaparinux, idraparinux and idrabiotaparinux, and parenteral direct thrombin inhibitors. The several shortcomings of unfractionated heparin and of low-molecular-weight heparins have prompted the development of the other newer agents. Here we review the mechanisms of action, pharmacological properties and side effects of parenteral anticoagulants used in the management of coronary heart disease treated with or without percutaneous coronary interventions, cardioversion for atrial fibrillation, and prosthetic heart valves and valve repair. Using an evidence-based approach, we describe the results of completed clinical trials, highlight ongoing research with currently available agents, and recommend therapeutic options for specific heart diseases.
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| 25. |
- De Caterina, Raffaele, et al.
(författare)
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Vitamin K antagonists in heart disease : Current status and perspectives (Section III)
- 2013
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 110:6, s. 1087-1107
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Tidskriftsartikel (refereegranskat)abstract
- Oral anticoagulants are a mainstay of cardiovascular therapy, and for over 60 years vitamin K antagonists (VKAs) were the only available agents for long-term use. VKAs interfere with the cyclic inter-conversion of vitamin K and its 2,3 epoxide, thus inhibiting gamma-carboxylation of glutamate residues at the amino-termini of vitamin K-dependent proteins, including the coagulation factors (F) II (prothrombin), VII, IX and X, as well as of the anticoagulant proteins C, S and Z. The overall effect of such interference is a dose-dependent anticoagulant effect, which has been therapeutically exploited in heart disease since the early 1950s. In this position paper, we review the mechanisms of action, pharmacological properties and side effects of VKAs, which are used in the management of cardiovascular diseases, including coronary heart disease (where their use is limited), stroke prevention in atrial fibrillation, heart valves and/or chronic heart failure. Using an evidence-based approach, we describe the results of completed clinical trials, highlight areas of uncertainty, and recommend therapeutic options for specific disorders. Although VKAs are being increasingly replaced in most patients with non-valvular atrial fibrillation by the new oral anticoagulants, which target either thrombin or FXa, the VKAs remain the agents of choice for patients with atrial fibrillation in the setting of rheumatic valvular disease and for those with mechanical heart valves.
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| 26. |
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| 27. |
- Dias, Pedro, et al.
(författare)
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Geophysical investigation of the down-dip extension of the Lombador massive sulphide deposit, Neves-Corvo, Portugal
- 2021
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Ingår i: International journal of earth sciences. - : Springer Nature. - 1437-3254 .- 1437-3262. ; 110:3, s. 911-922
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Tidskriftsartikel (refereegranskat)abstract
- The 150 Mt Lombador massive sulphide deposit is one of the seven known deposits of the Neves-Corvo mine. The deposit dips approximately 30o-35o to the NE and is open down dip, with current exploitation reaching down at 1 km depth. To investigate the possible downwards continuation of the deposit, a 1D constrained inversion of time-domain electromagnetic (TEM) ground loop data was conducted, followed by 3D electromagnetic (EM) forward modeling and a constrained 3D gravimetric inversion over the same area. To perform the EM and gravity modeling/inversion, a 3D geologic model was built using a density database comprising of approximately 300 drill-holes, and an electrical conductivity database with measurements from resistivity surveys and 1D inversion of the TEM data. The EM modeling shows that the Neves Formation shales are a regional conductive layer extending down to approximately 1.6 km depth in the Lombador area. This layer, often topped by massive sulphides, has an average density of 2.83 g/cm(3), whereas stockwork and massive sulphide reach on average 3.1 g/cm(3) and 4.5 g/cm(3), respectively. The 3D constrained gravity inversion results do not support the hypothesis of the presence of massive sulphides located in the down-dip direction of the Lombador deposit in the immediate vicinity of the known deposit. The lack of spatial resolution of the gravity grid, the study area limited size and the lack of information from within the basement suggest further studies are required to confirm the presence and amount of stockwork mineralization down-dip the Lombador deposit inside the Neves-Formation or the Phyllite-Quartzite basement.
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| 28. |
- Donis, Daphne, et al.
(författare)
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Stratification strength and light climate explain variation in chlorophyll a at the continental scale in a European multilake survey in a heatwave summer
- 2021
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Ingår i: Limnology and Oceanography. - : John Wiley & Sons. - 0024-3590 .- 1939-5590. ; 66:12, s. 4314-4333
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Tidskriftsartikel (refereegranskat)abstract
- To determine the drivers of phytoplankton biomass, we collected standardized morphometric, physical, and biological data in 230 lakes across the Mediterranean, Continental, and Boreal climatic zones of the European continent. Multilinear regression models tested on this snapshot of mostly eutrophic lakes (median total phosphorus [TP] = 0.06 and total nitrogen [TN] = 0.7 mg L-1), and its subsets (2 depth types and 3 climatic zones), show that light climate and stratification strength were the most significant explanatory variables for chlorophyll a (Chl a) variance. TN was a significant predictor for phytoplankton biomass for shallow and continental lakes, while TP never appeared as an explanatory variable, suggesting that under high TP, light, which partially controls stratification strength, becomes limiting for phytoplankton development. Mediterranean lakes were the warmest yet most weakly stratified and had significantly less Chl a than Boreal lakes, where the temperature anomaly from the long-term average, during a summer heatwave was the highest (+4 degrees C) and showed a significant, exponential relationship with stratification strength. This European survey represents a summer snapshot of phytoplankton biomass and its drivers, and lends support that light and stratification metrics, which are both affected by climate change, are better predictors for phytoplankton biomass in nutrient-rich lakes than nutrient concentrations and surface temperature.
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| 29. |
- Ekblom, Anneli, 1969-
(författare)
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Changing Landscapes : An Environmental History of Chibuene, Southern Mozambique
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis analyses the dynamics of environmental change and its embeddedness in the long term interactions of social history and rainfall variability through the building of an environmental history of the Chibuene locality, the coastal plain of southern Mozambique, 5 km south of the town Vilanculos, from 400 AD to present day. Land-use practices over time are discussed on the basis of vegetation and land-use history based pollen analysis, charcoal influx and diatom analysis. It is shown that the savanna vegetation is a long term feature of the Chibuene landscapes and that there have been several expansions of savannas and subsequent retractions of forests through time, linked primarily with rainfall variation. Written sources and archaeological material are drawn upon for a discussion on changing practices of environmental management and it is argued that as the Chibuene landscape is marked by a high degree of environmental insecurity, it is the competent management of resources that has enabled the continuous occupation of Chibuene from c. the 7th century AD, through management of natural resources, flexible farming practices and wide reaching social networks. The last two decades have seen a marked change in land-use patterns, reflected in a decrease in forests of the Chibuene area, the reasons for which are complex and needs to be further studied. Interviews with individual elders in the village community provide alternative ways of understanding environmental degradation as merely the loss of disappearance of forests, or the failure of crops due to droughts, but also as the erosion of local power, wars and social unrest. In a similar way, through a long-term perspective this study stresses that socio-political life, climatic variability and environmental dynamics are interlinked, highlighting the importance of the complimentarity of different forms of knowledge and ways of knowing the Chibuene landscape.
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| 30. |
- Ferreira, P. M., et al.
(författare)
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Collider phenomenology of new neutral scalars in a flavored multi-Higgs model
- 2023
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Ingår i: Physical Review D. - 2470-0010. ; 107:9
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Tidskriftsartikel (refereegranskat)abstract
- In this work, we propose and explore for the first time a new collider signature of heavy neutral scalars typically found in many distinct classes of multi-Higgs models. This signature, particularly relevant in the context of the Large Hadron Collider (LHC) measurements, is based on a topology with two charged leptons and four jets arising from first and second generation quarks. As an important benchmark scenario of the multi-Higgs models, we focus on a recently proposed Branco-Grimus-Lavoura (BGL) type model enhanced with an Abelian U(1) flavor symmetry and featuring an additional sector of right-handed neutrinos. We discuss how kinematics of the scalar fields in this model can be used to efficiently separate the signal from the dominant backgrounds and explore the discovery potential of the new heavy scalars in the forthcoming LHC runs. The proposed method can be applied for analysis of the statistical significance of heavy scalars' production at the LHC and future colliders in any multi-Higgs model.
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