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| 2. |
- Bazigou, Eleni, et al.
(författare)
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Genes regulating lymphangiogenesis control venous valve formation and maintenance in mice.
- 2011
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 121:8
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Tidskriftsartikel (refereegranskat)abstract
- Chronic venous disease and venous hypertension are common consequences of valve insufficiency, yet the molecular mechanisms regulating the formation and maintenance of venous valves have not been studied. Here, we provide what we believe to be the first description of venous valve morphogenesis and identify signaling pathways required for the process. The initial stages of valve development were found to involve induction of ephrin-B2, a key marker of arterial identity, by venous endothelial cells. Intriguingly, developing and mature venous valves also expressed a repertoire of proteins, including prospero-related homeobox 1 (Prox1), Vegfr3, and integrin-α9, previously characterized as specific and critical regulators of lymphangiogenesis. Using global and venous valve-selective knockout mice, we further demonstrate the requirement of ephrin-B2 and integrin-α9 signaling for the development and maintenance of venous valves. Our findings therefore identified molecular regulators of venous valve development and maintenance and highlighted the involvement of common morphogenetic processes and signaling pathways in controlling valve formation in veins and lymphatic vessels. Unexpectedly, we found that venous valve endothelial cells closely resemble lymphatic (valve) endothelia at the molecular level, suggesting plasticity in the ability of a terminally differentiated endothelial cell to take on a different phenotypic identity.
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- Clough, Rachel E, et al.
(författare)
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Endovascular treatment of acute aortic syndrome
- 2011
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Ingår i: Journal of Vascular Surgery. - : Elsevier BV. - 0741-5214 .- 1097-6809. ; 54:6, s. 1580-1587
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The term acute aortic syndrome (AAS) encompasses a range of conditions that have a risk of imminent aortic rupture and where delays in treatment result in increased mortality. Endovascular treatment offers an attractive alternative to open surgery but little is known about the durability of the repair and the factors that predict mortality. METHODS: Prospective data were collected for a cohort of 110 consecutive patients with endovascular treatment for AAS. Patient and procedural characteristics were related to short- and midterm outcome using multivariate logistic regression analysis. RESULTS: There were 75 men and 35 women with a median age of 68 (range 57-76) years. The pathologies treated were acute dissection (35), symptomatic aneurysm (32), infected aneurysm (18), transection (12), chronic dissection (9), penetrating ulcer (3), and intramural hematoma (1). Thirty-day mortality was 12.7% and this was associated with hypotension (odds ratio [OR], 5.25), use of general anesthetic (OR, 5.23), long procedure duration (OR, 2.03), and increasing age (OR, 1.07). The causes of death were aortic rupture (4), myocardial infarction (4), stroke (3), and multisystem organ failure (3). The stroke and paraplegia rates were 7.3% and 6.4%, respectively. The 1-year survival was 81% and the 5-year survival 63%. Secondary procedures were required in 13 (11.8%) patients. Factors associated with death at 1 year were presence of an aortic fistula (OR, 9.78), perioperative stroke (OR, 5.87), and use of general anesthetic (OR, 3.76); and at 5 years were aortic fistula (OR, 12.31) and increasing age (OR, 1.06). CONCLUSIONS: Acute aortic syndrome carries significant early and late mortality. Emergency endovascular repair offers a minimally invasive treatment option associated with acceptable short and midterm results. Continued surveillance is important as secondary procedures and aortic-related deaths continue to occur throughout the follow-up period.
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- Geerts, Jaason M., et al.
(författare)
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Guidance for Health Care Leaders During the Recovery Stage of the COVID-19 Pandemic A Consensus Statement
- 2021
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Ingår i: JAMA Network Open. - : American Medical Association. - 2574-3805. ; 4:7
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The COVID-19 pandemic is the greatest global test of health leadership of our generation. There is an urgent need to provide guidance for leaders at all levels during the unprecedented preresolution recovery stage.OBJECTIVE: To create an evidence- and expertise-informed framework of leadership imperatives to serve as a resource to guide health and public health leaders during the postemergency stage of the pandemic.EVIDENCE REVIEW: A literature search in PubMed, MEDLINE, and Embase revealed 10 910 articles published between 2000 and 2021 that included the terms leadership and variations of emergency, crisis, disaster, pandemic, COVID-19, or public health. Using the Standards for Quality Improvement Reporting Excellence reporting guideline for consensus statement development, this assessment adopted a 6-round modified Delphi approach involving 32 expert coauthors from 17 countries who participated in creating and validating a framework outlining essential leadership imperatives.FINDINGS: The 10 imperatives in the framework are; (1) acknowledge staff and celebrate successes; (2) provide support for staff well-being; (3) develop a clear understanding of the current local and global context, along with informed projections; (4) prepare for future emergencies (personnel, resources, protocols, contingency plans, coalitions, and training); (5) reassess priorities explicitly and regularly and provide purpose, meaning, and direction; (6) maximize team, organizational, and system performance and discuss enhancements; (7) manage the backlog of paused services and consider improvements while avoiding burnout and moral distress; (8) sustain learning, innovations, and collaborations, and imagine future possibilities; (9) provide regular communication and engender trust; and (10) in consultation with public health and fellow leaders, provide safety information and recommendations to government, other organizations, staff, and the community to improve equitable and integrated care and emergency preparedness systemwide.CONCLUSIONS AND RELEVANCE: Leaders who most effectively implement these imperatives are ideally positioned to address urgent needs and inequalities in health systems and to cocreate with their organizations a future that best serves stakeholders and communities.
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| 11. |
- Lyons, Oliver, et al.
(författare)
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Human venous valve disease caused by mutations in FOXC2 and GJC2
- 2017
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 214:8, s. 2437-2452
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Tidskriftsartikel (refereegranskat)abstract
- Venous valves (VVs) prevent venous hypertension and ulceration. We report that FOXC2 and GJC2 mutations are associated with reduced VV number and length. In mice, early VV formation is marked by elongation and reorientation ("organization") of Prox1(hi) endothelial cells by postnatal day 0. The expression of the transcription factors Foxc2 and Nfatc1 and the gap junction proteins Gjc2, Gja1, and Gja4 were temporospatially regulated during this process. Foxc2 and Nfatc1 were coexpressed at P0, and combined Foxc2 deletion with calcineurin-Nfat inhibition disrupted early Prox1(hi) endothelial organization, suggesting cooperative Foxc2-Nfatc1 patterning of these events. Genetic deletion of Gjc2, Gja4, or Gja1 also disrupted early VV Prox1(hi) endothelial organization at postnatal day 0, and this likely underlies the VV defects seen in patients with GJC2 mutations. Knockout of Gja4 or Gjc2 resulted in reduced proliferation of Prox1(hi) valve-forming cells. At later stages of blood flow, Foxc2 and calcineurin-Nfat signaling are each required for growth of the valve leaflets, whereas Foxc2 is not required for VV maintenance.
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| 12. |
- Lyons, Oliver, et al.
(författare)
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Mutations in EPHB4 cause human venous valve aplasia
- 2021
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Ingår i: JCI Insight. - : American Society For Clinical Investigation. - 2379-3708. ; 6:18
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Tidskriftsartikel (refereegranskat)abstract
- Venous valve (VV) failure causes chronic venous insufficiency, but the molecular regulation of valve development is poorly understood. A primary lymphatic anomaly, caused by mutations in the receptor tyrosine kinase EPHB4, was recently described, with these patients also presenting with venous insufficiency. Whether the venous anomalies are the result of an effect on VVs is not known. VV formation requires complex "organization" of valve-forming endothelial cells, including their reorientation perpendicular to the direction of blood flow. Using quantitative ultrasound, we identified substantial VV aplasia and deep venous reflux in patients with mutations in EPHB4. We used a GFP reporter in mice to study expression of its ligand, ephrinB2, and analyzed developmental phenotypes after conditional deletion of floxed Ephb4 and Efnb2 alleles. EphB4 and ephrinB2 expression patterns were dynamically regulated around organizing valve-forming cells. Efnb2 deletion disrupted the normal endothelial expression patterns of the gap junction proteins connexin37 and connexin43 (both required for normal valve development) around reorientating valve-forming cells and produced deficient valve-forming cell elongation, reorientation, polarity, and proliferation. Ephb4 was also required for valve-forming cell organization and subsequent growth of the valve leaflets. These results uncover a potentially novel cause of primary human VV aplasia.
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- Murari, A., et al.
(författare)
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A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
- 2024
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Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
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| 17. |
- Sörelius, Karl, et al.
(författare)
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Endovascular treatment of mycotic aortic aneurysms: a European multicenter study.
- 2014
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 1524-4539 .- 0009-7322. ; 130:24, s. 2136-42
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Tidskriftsartikel (refereegranskat)abstract
- Mycotic aortic aneurysm (MAA) is a rare and life-threatening disease. The aim of this European multicenter collaboration was to study the durability of endovascular aortic repair (EVAR) of MAA, by assessing late infection-related complications and long-term survival.
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| 22. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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| 23. |
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