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- Spronk, H. M. H., et al.
(author)
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Atherothrombosis and Thromboembolism : Position Paper from the Second Maastricht Consensus Conference on Thrombosis
- 2018
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In: Thrombosis and Haemostasis. - : SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN. - 0340-6245 .- 2567-689X. ; 118:2, s. 229-250
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Research review (peer-reviewed)abstract
- Atherothrombosis is a leading cause of cardiovascular mortality and long-term morbidity. Platelets and coagulation proteases, interacting with circulating cells and in different vascular beds, modify several complex pathologies including atherosclerosis. In the second Maastricht Consensus Conference on Thrombosis, this theme was addressed by diverse scientists from bench to bedside. All presentations were discussed with audience members and the results of these discussions were incorporated in the final document that presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following five topics:1. Risk factors, biomarkers and plaque instability: In atherothrombosis research, more focus on the contribution of specific risk factors like ectopic fat needs to be considered; definitions of atherothrombosis are important distinguishing different phases of disease, including plaque (in) stability; proteomic and metabolomics data are to be added to genetic information.2. Circulating cells including platelets and atherothrombosis: Mechanisms of leukocyte and macrophage plasticity, migration, and transformation in murine atherosclerosis need to be considered; diseasemechanism-based biomarkers need to be identified; experimental systems are needed that incorporatewhole-blood flow to understand how red blood cells influence thrombus formation and stability; knowledge on platelet heterogeneity and priming conditions needs to be translated toward the in vivo situation.3. Coagulation proteases, fibrin(ogen) and thrombus formation: The role of factor (F) XI in thrombosis including the lower margins of this factor related to safe and effective antithrombotic therapy needs to be established; FXI is a key regulator in linking platelets, thrombin generation, and inflammatory mechanisms in a renin-angiotensin dependent manner; however, the impact on thrombin-dependent PAR signaling needs further study; the fundamental mechanisms in FXIII biology and biochemistry and its impact on thrombus biophysical characteristics need to be explored; the interactions of red cells and fibrin formation and its consequences for thrombus formation and lysis need to be addressed. Platelet-fibrin interactions are pivotal determinants of clot formation and stability with potential therapeutic consequences.4. Preventive and acute treatment of atherothrombosis and arterial embolism; novel ways and tailoring? The role of protease-activated receptor (PAR)-4 vis a vis PAR-1 as target for antithrombotic therapy merits study; ongoing trials on platelet function test-based antiplatelet therapy adjustment support development of practically feasible tests; risk scores for patients with atrial fibrillation need refinement, taking new biomarkers including coagulation into account; risk scores that consider organ system differences in bleeding may have added value; all forms of oral anticoagulant treatment require better organization, including education and emergency access; laboratory testing still needs rapidly available sensitive tests with short turnaround time.5. Pleiotropy of coagulation proteases, thrombus resolution and ischaemia-reperfusion: Biobanks specifically for thrombus storage and analysis are needed; further studies on novelmodified activated protein C-based agents are required including its cytoprotective properties; new avenues for optimizing treatment of patients with ischaemic stroke are needed, also including novel agents that modify fibrinolytic activity (aimed at plasminogen activator inhibitor-1 and thrombin activatable fibrinolysis inhibitor.
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- Spronk, Inge, et al.
(author)
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Improved and standardized method for assessing years lived with disability after burns and its application to estimate the non-fatal burden of disease of burn injuries in Australia, New Zealand and the Netherlands
- 2020
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In: BMC Public Health. - : BMC. - 1471-2458. ; 20
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Journal article (peer-reviewed)abstract
- Background: Burden of disease estimates are an important resource in public health. Currently, robust estimates are not available for the burn population. Our objectives are to adapt a refined methodology (INTEGRIS method) to burns and to apply this new INTEGRIS-burns method to estimate, and compare, the burden of disease of burn injuries in Australia, New Zealand and the Netherlands.Methods: Existing European and Western-Australian health-related quality of life (HRQL) datasets were combined to derive disability weights for three homogenous burn injury groups based on percentage total body surface area (%TBSA) burned. Subsequently, incidence data from Australia, New Zealand, and the Netherlands from 2010 to 2017 were used to compute annual non-fatal burden of disease estimates for each of these three countries. Non-fatal burden of disease was measured by years lived with disability (YLD).Results: The combined dataset included 7159 HRQL (EQ-5D-3 L) outcomes from 3401 patients. Disability weights ranged from 0.046 (subgroup < 5% TBSA burned > 24 months post-burn) to 0.497 (subgroup > 20% TBSA burned 0-1 months post-burn). In 2017 the non-fatal burden of disease of burns for the three countries (YLDs/100,000 inhabitants) was 281 for Australia, 279 for New Zealand and 133 for the Netherlands.Conclusions: This project established a method for more precise estimates of the YLDs of burns, as it is the only method adapted to the nature of burn injuries and their recovery. Compared to previous used methods, the INTEGRIS-burns method includes improved disability weights based on severity categorization of burn patients; a better substantiated proportion of patients with lifelong disability based; and, the application of burn specific recovery timeframes. Information derived from the adapted method can be used as input for health decision making at both the national and international level. Future studies should investigate whether the application is valid in low- and middle- income countries.
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- Sproson, Adam D., et al.
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Osmium and lithium isotope evidence for weathering feedbacks linked to orbitally paced organic carbon burial and Silurian glaciations
- 2022
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In: Earth and Planetary Science Letters. - : Elsevier BV. - 0012-821X. ; 577
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Journal article (peer-reviewed)abstract
- The Ordovician (∼487 to 443 Ma) ended with the formation of extensive Southern Hemisphere ice sheets, known as the Hirnantian glaciation, and the second largest mass extinction in Earth History. It was followed by the Silurian (∼443 to 419 Ma), one of the most climatically unstable periods of the Phanerozoic as evidenced by several large scale (>5‰) carbon isotope (δ13C) perturbations associated with further extinction events. Despite several decades of research, the cause of these environmental instabilities remains enigmatic. Here, we provide osmium (187Os/188Os) and lithium (δ7Li) isotope measurements of marine sedimentary rocks that cover four Silurian δ13C excursions. Osmium and Li isotope records resemble those previously recorded for the Hirnantian glaciation suggesting a similar causal mechanism. When combined with a new dynamic carbon-osmium-lithium biogeochemical model we suggest that astronomical forcing of the marine organic carbon cycle, as opposed to a decline in volcanic arc degassing or the rise of early land plants, resulted in drawdown of atmospheric CO2, triggering continental scale glaciation, intense global cooling and eustatic sea-level lows recognised in the geological record. Lower atmospheric pCO2 and temperatures during the Hirnantian and Silurian glaciations suppressed CO2 removal by silicate weathering, driving 187Os/188Os and δ7Li variability, supporting the existence of climate-regulating feedbacks.
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- Sproson, David, et al.
(author)
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Modelling the impact of Baltic Sea upwelling on the atmospheric boundary layer
- 2014
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In: Tellus. Series A, Dynamic meteorology and oceanography. - : Stockholm University Press. - 0280-6495 .- 1600-0870. ; 66, s. 24041-
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Journal article (peer-reviewed)abstract
- Coastal upwelling, with a strong sea-surface temperature (SST) signal, is extremely common in the Baltic Sea during the summer months. Although the spatial scale of upwelling is small, its high frequency of occurrence in the semi-enclosed basin may allow the SST signature to have significant feedback onto the lower atmosphere. In this paper, we develop a method to remove the signature of upwelling from SST fields, and use these modified SST fields as the lower boundary condition of an atmospheric model, allowing us to evaluate the importance of coastal upwelling to the mean summer conditions over the Baltic. The contribution of upwelling is found to be small generally, although significant locally over areas where upwelling is most common. This includes 2 m air temperature reductions of up to 2°C, wind speed reductions of up to 0.25 m s−1, and reductions in the mean boundary-layer height of up to 100 m. High-resolution simulations with artificially enhanced upwelling suggest that upwelling may become increasingly important as winds slacken at the end of an upwelling period.
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