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- Glasbey, JC, et al.
(author)
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- 2021
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swepub:Mat__t
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- Tabiri, S, et al.
(author)
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- 2021
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swepub:Mat__t
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- Bravo, L, et al.
(author)
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- 2021
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swepub:Mat__t
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- Khatri, C, et al.
(author)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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In: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Journal article (peer-reviewed)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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- Hobirk, J., et al.
(author)
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The JET hybrid scenario in Deuterium, Tritium and Deuterium-Tritium
- 2023
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In: Nuclear Fusion. - : Institute of Physics Publishing (IOPP). - 0029-5515 .- 1741-4326. ; 63:11
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Journal article (peer-reviewed)abstract
- The JET hybrid scenario has been developed from low plasma current carbon wall discharges to the record-breaking Deuterium-Tritium plasmas obtained in 2021 with the ITER-like Be/W wall. The development started in pure Deuterium with refinement of the plasma current, and toroidal magnetic field choices and succeeded in solving the heat load challenges arising from 37 MW of injected power in the ITER like wall environment, keeping the radiation in the edge and core controlled, avoiding MHD instabilities and reaching high neutron rates. The Deuterium hybrid plasmas have been re-run in Tritium and methods have been found to keep the radiation controlled but not at high fusion performance probably due to time constraints. For the first time this scenario has been run in Deuterium-Tritium (50:50). These plasmas were re-optimised to have a radiation-stable H-mode entry phase, good impurity control through edge Ti gradient screening and optimised performance with fusion power exceeding 10 MW for longer than three alpha particle slow down times, 8.3 MW averaged over 5 s and fusion energy of 45.8 MJ.
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- Birken, Sarah A., et al.
(author)
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Toward a more comprehensive understanding of organizational influences on implementation: the organization theory for implementation science framework
- 2023
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In: FRONTIERS IN HEALTH SERVICES. - : FRONTIERS MEDIA SA. - 2813-0146. ; 3
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Journal article (peer-reviewed)abstract
- IntroductionImplementation is influenced by factors beyond individual clinical settings. Nevertheless, implementation research often focuses on factors related to individual providers and practices, potentially due to limitations of available frameworks. Extant frameworks do not adequately capture the myriad organizational influences on implementation. Organization theories capture diverse organizational influences but remain underused in implementation science. To advance their use among implementation scientists, we distilled 70 constructs from nine organization theories identified in our previous work into theoretical domains in the Organization Theory for Implementation Science (OTIS) framework.MethodsThe process of distilling organization theory constructs into domains involved concept mapping and iterative consensus-building. First, we recruited organization and implementation scientists to participate in an online concept mapping exercise in which they sorted organization theory constructs into domains representing similar theoretical concepts. Multidimensional scaling and hierarchical cluster analyses were used to produce visual representations (clusters) of the relationships among constructs in concept maps. Second, to interpret concept maps, we engaged members of the Cancer Prevention and Control Research Network (CPCRN) OTIS workgroup in consensus-building discussions.ResultsTwenty-four experts participated in concept mapping. Based on resulting construct groupings coherence, OTIS workgroup members selected the 10-cluster solution (from options of 7-13 clusters) and then reorganized clusters in consensus-building discussions to increase coherence. This process yielded six final OTIS domains: organizational characteristics (e.g., size; age); governance and operations (e.g., organizational and social subsystems); tasks and processes (e.g., technology cycles; excess capacity); knowledge and learning (e.g., tacit knowledge; sense making); characteristics of a population of organizations (e.g., isomorphism; selection pressure); and interorganizational relationships (e.g., dominance; interdependence).DiscussionOrganizational influences on implementation are poorly understood, in part due to the limitations of extant frameworks. To improve understanding of organizational influences on implementation, we distilled 70 constructs from nine organization theories into six domains. Applications of the OTIS framework will enhance understanding of organizational influences on implementation, promote theory-driven strategies for organizational change, improve understanding of mechanisms underlying relationships between OTIS constructs and implementation, and allow for framework refinement. Next steps include testing the OTIS framework in implementation research and adapting it for use among policymakers and practitioners.
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- Peluso, A. Augusto, et al.
(author)
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Functional assay for assessment of agonistic or antagonistic activity of angiotensin AT2 receptor ligands reveals that EMA401 and PD123319 have agonistic properties
- 2023
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In: Biochemical Pharmacology. - : Elsevier BV. - 0006-2952 .- 1356-1839. ; 216
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Journal article (peer-reviewed)abstract
- With the discovery of the protective arm of the renin-angiotensin system (RAS), interest has grown in protective RAS-related receptors such as the angiotensin AT2-receptor [AT2R] as potential new drug targets. While it is known that AT2R couple to Gi, it is also apparent that they do not signal via inhibition of adenylyl cyclase/ decrease in cAMP, as do many Gi-coupled receptors. Thus, standard commercially-available assays cannot be applied to test for agonistic or antagonistic properties of AT2R ligands. This lack of standard assays has hampered the development of new drugs targeting the AT2R.Therefore, we aimed at developing a reliable, technically easy assay for the determination of intrinsic activity of AT2R ligands, primarily for distinguishing between AT2R agonists and antagonists. We found that measure-ment of NO release by DAF-FM fluorescence in primary human aortic endothelial cells (HAEC) or in AT2R-transfected CHO cells is a reliable assay for the characterization of AT2R ligands. While testing the assay, we made several novel findings, including: a) C21 is a full agonist at the AT2R (with the same efficacy as angiotensin II); b) C21 has no intrinsic activity at the receptor Mas; c) AT2R-transfected HEK-293 cells are unresponsive to AT2R stimulation; d) EMA401 and PD123319, which are commonly regarded as AT2R antagonists, are partial agonists at the AT2R.Collectively, we have developed and tested an assay based on the measurement and quantification of NO release in HAEC or in AT2R-CHO cells that is suitable for the characterisation of novel and established AT2R ligands.
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