| 1. |
- Ederle, Joerg, et al.
(författare)
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Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
- 2010
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Ingår i: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
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Tidskriftsartikel (refereegranskat)abstract
- Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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| 2. |
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| 3. |
- Abdo, A. A., et al.
(författare)
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Gamma-ray emission concurrent with the nova in the symbiotic binary V407 cygni
- 2010
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 329:5993, s. 817-821
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Tidskriftsartikel (refereegranskat)abstract
- Novae are thermonuclear explosions on a white dwarf surface fueled by mass accreted from a companion star. Current physical models posit that shocked expanding gas from the nova shell can produce x-ray emission, but emission at higher energies has not been widely expected. Here, we report the Fermi Large Area Telescope detection of variable γ-ray emission (0.1 to 10 billion electron volts) from the recently detected optical nova of the symbiotic star V407 Cygni. We propose that the material of the nova shell interacts with the dense ambient medium of the red giant primary and that particles can be accelerated effectively to produce π0 decay γ-rays from proton-proton interactions. Emission involving inverse Compton scattering of the red giant radiation is also considered and is not ruled out.
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| 4. |
- Chalmers, J. R., et al.
(författare)
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Report from the fourth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative)
- 2016
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Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 175:1, s. 69-79
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Tidskriftsartikel (refereegranskat)abstract
- This article is a report of the fourth meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in Malmo, Sweden on 23-24 April 2015 (HOME IV). The aim of the meeting was to achieve consensus over the preferred outcome instruments for measuring patient-reported symptoms and quality of life for the HOME core outcome set for atopic eczema (AE). Following presentations, which included data from systematic reviews, consensus discussions were held in a mixture of whole group and small group discussions. Small groups were allocated a priori to ensure representation of different stakeholders and countries. Decisions were voted on using electronic keypads. For the patient-reported symptoms, the group agreed by vote that itch, sleep loss, dryness, redness/inflamed skin and irritated skin were all considered essential aspects of AE symptoms. Many instruments for capturing patient-reported symptoms were discussed [ including the Patient-Oriented SCOring Atopic Dermatitis index, Patient-Oriented Eczema Measure (POEM), Self-Administered Eczema Area and Severity Index, Itch Severity Scale, Atopic Dermatitis Quickscore and the Nottingham Eczema Severity Score] and, by consensus, POEM was selected as the preferred instrument to measure patient-reported symptoms. Further work is needed to determine the reliability and measurement error of POEM. Further work is also required to establish the importance of pain/soreness and the importance of collecting information regarding the intensity of symptoms in addition to their frequency. Much of the discussion on quality of life concerned the Dermatology Life Quality Index and Quality of Life Index for Atopic Dermatitis; however, consensus on a preferred instrument for measuring this domain could not be reached. In summary, POEM is recommended as the HOME core outcome instrument for measuring AE symptoms.
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| 5. |
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| 6. |
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| 7. |
- Bozzola, Tiago, et al.
(författare)
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Sialic Acid Derivatives Inhibit SiaT Transporters and Delay Bacterial Growth
- 2022
-
Ingår i: Acs Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 17:7, s. 1890-1900
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Tidskriftsartikel (refereegranskat)abstract
- Antibiotic resistance is a major worldwide concern, and new drugs with mechanistically novel modes of action are urgently needed. Here, we report the structure-based drug design, synthesis, and evaluation in vitro and in cellular systems of sialic acid derivatives able to inhibit the bacterial sialic acid symporter SiaT. We designed and synthesized 21 sialic acid derivatives and screened their affinity for SiaT by a thermal shift assay and elucidated the inhibitory mechanism through binding thermodynamics, computational methods, and inhibitory kinetic studies. The most potent compounds, which have a 180-fold higher affinity compared to the natural substrate, were tested in bacterial growth assays and indicate bacterial growth delay in methicillin-resistant Staphylococcus aureus. This study represents the first example and a promising lead in developing sialic acid uptake inhibitors as novel antibacterial agents.
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| 8. |
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| 9. |
- Hachinski, Vladimir, et al.
(författare)
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Stroke: Working Toward a Prioritized World Agenda
- 2010
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Ingår i: Stroke: a journal of cerebral circulation. - 1524-4628. ; 41:6, s. 1084-1099
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-The aim of the Synergium was to devise and prioritize new ways of accelerating progress in reducing the risks, effects, and consequences of stroke. Methods-Preliminary work was performed by 7 working groups of stroke leaders followed by a synergium (a forum for working synergistically together) with approximately 100 additional participants. The resulting draft document had further input from contributors outside the synergium. Results-Recommendations of the Synergium are: Basic Science, Drug Development and Technology: There is a need to develop: (1) New systems of working together to break down the prevalent "silo" mentality; (2) New models of vertically integrated basic, clinical, and epidemiological disciplines; and (3) Efficient methods of identifying other relevant areas of science. Stroke Prevention: (1) Establish a global chronic disease prevention initiative with stroke as a major focus. (2) Recognize not only abrupt clinical stroke, but subtle subclinical stroke, the commonest type of cerebrovascular disease, leading to impairments of executive function. (3) Develop, implement and evaluate a population approach for stroke prevention. (4) Develop public health communication strategies using traditional and novel (eg, social media/marketing) techniques. Acute Stroke Management: Continue the establishment of stroke centers, stroke units, regional systems of emergency stroke care and telestroke networks. Brain Recovery and Rehabilitation: (1) Translate best neuroscience, including animal and human studies, into poststroke recovery research and clinical care. (2) Standardize poststroke rehabilitation based on best evidence. (3) Develop consensus on, then implementation of, standardized clinical and surrogate assessments. (4) Carry out rigorous clinical research to advance stroke recovery. Into the 21st Century: Web, Technology and Communications: (1) Work toward global unrestricted access to stroke-related information. (2) Build centralized electronic archives and registries. Foster Cooperation Among Stakeholders (large stroke organizations, nongovernmental organizations, governments, patient organizations and industry) to enhance stroke care. Educate and energize professionals, patients, the public and policy makers by using a "Brain Health" concept that enables promotion of preventive measures. Conclusions-To accelerate progress in stroke, we must reach beyond the current status scientifically, conceptually, and pragmatically. Advances can be made not only by doing, but ceasing to do. Significant savings in time, money, and effort could result from discontinuing practices driven by unsubstantiated opinion, unproven approaches, and financial gain. Systematic integration of knowledge into programs coupled with careful evaluation can speed the pace of progress.
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| 10. |
- Hachinski, Vladimir, et al.
(författare)
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Stroke: Working toward a Prioritized World Agenda
- 2010
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Ingår i: Cerebrovascular Diseases. - : S. Karger AG. - 1421-9786 .- 1015-9770. ; 30:2, s. 127-147
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: The aim of the Synergium was to devise and prioritize new ways of accelerating progress in reducing the risks, effects, and consequences of stroke. Methods: Preliminary work was performed by 7 working groups of stroke leaders followed by a synergium (a forum for working synergistically together) with approximately 100 additional participants. The resulting draft document had further input from contributors outside the synergium. Results: Recommendations of the Synergium are: Basic Science, Drug Development and Technology: There is a need to develop: (1) New systems of working together to break down the prevalent 'silo' mentality; (2) New models of vertically integrated basic, clinical, and epidemiological disciplines; and (3) Efficient methods of identifying other relevant areas of science. Stroke Prevention: (1) Establish a global chronic disease prevention initiative with stroke as a major focus. (2) Recognize not only abrupt clinical stroke, but subtle subclinical stroke, the commonest type of cerebrovascular disease, leading to impairments of executive function. (3) Develop, implement and evaluate a population approach for stroke prevention. (4) Develop public health communication strategies using traditional and novel (e. g., social media/marketing) techniques. Acute Stroke Management: Continue the establishment of stroke centers, stroke units, regional systems of emergency stroke care and telestroke networks. Brain Recovery and Rehabilitation: (1) Translate best neuroscience, including animal and human studies, into poststroke recovery research and clinical care. (2) Standardize poststroke rehabilitation based on best evidence. (3) Develop consensus on, then implementation of, standardized clinical and surrogate assessments. (4) Carry out rigorous clinical research to advance stroke recovery. Into the 21st Century: Web, Technology and Communications: (1) Work toward global unrestricted access to stroke-related information. (2) Build centralized electronic archives and registries. Foster Cooperation Among Stakeholders (large stroke organizations, nongovernmental organizations, governments, patient organizations and industry) to enhance stroke care. Educate and energize professionals, patients, the public and policy makers by using a 'Brain Health' concept that enables promotion of preventive measures. Conclusions: To accelerate progress in stroke, we must reach beyond the current status scientifically, conceptually, and pragmatically. Advances can be made not only by doing, but ceasing to do. Significant savings in time, money, and effort could result from discontinuing practices driven by unsubstantiated opinion, unproven approaches, and financial gain. Systematic integration of knowledge into programs coupled with careful evaluation can speed the pace of progress. Copyright (C) 2010 American Heart Association. Inc., S. Karger AG, Basel, and John Wiley & Sons, Inc.
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| 11. |
- Hachinski, Vladimir, et al.
(författare)
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Stroke: working toward a prioritized world agenda
- 2010
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Ingår i: International Journal of Stroke. - : SAGE Publications. - 1747-4949 .- 1747-4930. ; 5:4, s. 238-256
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and Purpose The aim of the Synergium was to devise and prioritize new ways of accelerating progress in reducing the risks, effects, and consequences of stroke. Methods Preliminary work was performed by seven working groups of stroke leaders followed by a synergium (a forum for working synergistically together) with approximately 100 additional participants. The resulting draft document had further input from contributors outside the synergium. Results Recommendations of the Synergium are: Basic Science, Drug Development and Technology: There is a need to develop: (1) New systems of working together to break down the prevalent 'silo' mentality; (2) New models of vertically integrated basic, clinical, and epidemiological disciplines; and (3) Efficient methods of identifying other relevant areas of science. Stroke Prevention: (1) Establish a global chronic disease prevention initiative with stroke as a major focus. (2) Recognize not only abrupt clinical stroke, but subtle subclinical stroke, the commonest type of cerebrovascular disease, leading to impairments of executive function. (3) Develop, implement and evaluate a population approach for stroke prevention. (4) Develop public health communication strategies using traditional and novel (eg, social media/marketing) techniques. Acute Stroke Management: Continue the establishment of stroke centers, stroke units, regional systems of emergency stroke care and telestroke networks. Brain Recovery and Rehabilitation: (1) Translate best neuroscience, including animal and human studies, into poststroke recovery research and clinical care. (2) Standardize poststroke rehabilitation based on best evidence. (3) Develop consensus on, then implementation of, standardized clinical and surrogate assessments. (4) Carry out rigorous clinical research to advance stroke recovery. Into the 21st Century: Web, Technology and Communications: (1) Work toward global unrestricted access to stroke-related information. (2) Build centralized electronic archives and registries. Foster Cooperation Among Stakeholders (large stroke organizations, nongovernmental organizations, governments, patient organizations and industry) to enhance stroke care. Educate and energize professionals, patients, the public and policy makers by using a 'Brain Health' concept that enables promotion of preventive measures. Conclusions To accelerate progress in stroke, we must reach beyond the current status scientifically, conceptually, and pragmatically. Advances can be made not only by doing, but ceasing to do. Significant savings in time, money, and effort could result from discontinuing practices driven by unsubstantiated opinion, unproven approaches, and financial gain. Systematic integration of knowledge into programs coupled with careful evaluation can speed the pace of progress.
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| 12. |
- Johansson, Linda C, 1983, et al.
(författare)
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Lipidic phase membrane protein serial femtosecond crystallography.
- 2012
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Ingår i: Nature methods. - : Springer Science and Business Media LLC. - 1548-7105 .- 1548-7091. ; 9:3, s. 263-265
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Tidskriftsartikel (refereegranskat)abstract
- X-ray free electron laser (X-FEL)-based serial femtosecond crystallography is an emerging method with potential to rapidly advance the challenging field of membrane protein structural biology. Here we recorded interpretable diffraction data from micrometer-sized lipidic sponge phase crystals of the Blastochloris viridis photosynthetic reaction center delivered into an X-FEL beam using a sponge phase micro-jet.
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| 13. |
- Lebzelter, T., et al.
(författare)
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Comparative modelling of the spectra of cool giants
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 547, s. A108-
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Tidskriftsartikel (refereegranskat)abstract
- Context. Our ability to extract information from the spectra of stars depends on reliable models of stellar atmospheres and appropriate techniques for spectral synthesis. Various model codes and strategies for the analysis of stellar spectra are available today. Aims. We aim to compare the results of deriving stellar parameters using different atmosphere models and different analysis strategies. The focus is set on high-resolution spectroscopy of cool giant stars. Methods. Spectra representing four cool giant stars were made available to various groups and individuals working in the area of spectral synthesis, asking them to derive stellar parameters from the data provided. The results were discussed at a workshop in Vienna in 2010. Most of the major codes currently used in the astronomical community for analyses of stellar spectra were included in this experiment. Results. We present the results from the different groups, as well as an additional experiment comparing the synthetic spectra produced by various codes for a given set of stellar parameters. Similarities and differences of the results are discussed. Conclusions. Several valid approaches to analyze a given spectrum of a star result in quite a wide range of solutions. The main causes for the differences in parameters derived by different groups seem to lie in the physical input data and in the details of the analysis method. This clearly shows how far from a definitive abundance analysis we still are.
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| 14. |
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| 15. |
- Ringleb, P, et al.
(författare)
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Extending the time window for intravenous thrombolysis in acute ischemic stroke using magnetic resonance imaging-based patient selection
- 2019
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Ingår i: International journal of stroke : official journal of the International Stroke Society. - : SAGE Publications. - 1747-4949. ; 14:5, s. 483-490
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Tidskriftsartikel (refereegranskat)abstract
- Intravenous thrombolysis with alteplase within a time window up to 4.5 h is the only approved pharmacological treatment for acute ischemic stroke. We studied whether acute ischemic stroke patients with penumbral tissue identified on magnetic resonance imaging 4.5–9 h after symptom onset benefit from intravenous thrombolysis compared to placebo. Methods Acute ischemic stroke patients with salvageable brain tissue identified on a magnetic resonance imaging were randomly assigned to receive standard dose alteplase or placebo. The primary end point was disability at 90 days assessed by the modified Rankin scale, which has a range of 0–6 (with 0 indicating no symptoms at all and 6 indicating death). Safety end points included death, symptomatic intracranial hemorrhage, and other serious adverse events. Results The trial was stopped early for slow recruitment after the enrollment of 119 (61 alteplase, 58 placebo) of 264 patients planned. Median time to intravenous thrombolysis was 7 h 42 min. The primary endpoint showed no significant difference in the modified Rankin scale distribution at day 90 (odds ratio alteplase versus placebo, 1.20; 95% CI, 0.63–2.27, P = 0.58). One symptomatic intracranial hemorrhage occurred in the alteplase group. Mortality at 90 days did not differ significantly between the two groups (11.5 and 6.8%, respectively; P = 0.53). Conclusions Intravenous alteplase administered between 4.5 and 9 h after the onset of symptoms in patients with salvageable tissue did not result in a significant benefit over placebo. (Supported by Boehringer Ingelheim, Germany; ISRCTN 71616222).
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| 16. |
- Sanchez, J. C., et al.
(författare)
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High-resolution crystal structures of amyxobacterial phytochrome at cryo and roomtemperatures
- 2019
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Ingår i: Structural Dynamics-Us. - : AIP Publishing. - 2329-7778. ; 6:5
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Tidskriftsartikel (refereegranskat)abstract
- Phytochromes (PHYs) are photoreceptor proteins first discovered in plants, where they control a variety of photomorphogenesis events. PHYs as photochromic proteins can reversibly switch between two distinct states: a red light (Pr) and a far-red light (Pfr) absorbing form. The discovery of Bacteriophytochromes (BphPs) in nonphotosynthetic bacteria has opened new frontiers in our understanding of the mechanisms by which these natural photoswitches can control single cell development, although the role of BphPs in vivo remains largely unknown. BphPs are dimeric proteins that consist of a photosensory core module (PCM) and an enzymatic domain, often a histidine kinase. The PCM is composed of three domains (PAS, GAF, and PHY). It holds a covalently bound open-chain tetrapyrrole (biliverdin, BV) chromophore. Upon absorption of light, the double bond between BV rings C and D isomerizes and reversibly switches the protein between Pr and Pfr states. We report crystal structures of the wild-type and mutant (His275Thr) forms of the canonical BphP from the nonphotosynthetic myxobacterium Stigmatella aurantiaca (SaBphP2) in the Pr state. Structures were determined at 1.65A degrees and 2.2A degrees (respectively), the highest resolution of any PCM construct to date. We also report the room temperature wild-type structure of the same protein determined at 2.1A degrees at the SPring-8 Angstrom Compact free electron LAser (SACLA), Japan. Our results not only highlight and confirm important amino acids near the chromophore that play a role in Pr-Pfr photoconversion but also describe the signal transduction into the PHY domain which moves across tens of angstroms after the light stimulus. (C) 2019 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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| 17. |
- Sorelius, Karl, et al.
(författare)
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The Microbiology of Infective Native Aortic Aneurysms in a Population-Based Setting
- 2022
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Ingår i: Annals of Vascular Surgery. - : Elsevier. - 0890-5096 .- 1615-5947. ; 78, s. 112-122
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim was to describe the microbiology of surgically treated infective native (mycotic) aortic aneurysms (INAAs), and associated survival and development of infection-related complications (IRCs). Methods: Data were pooled from 2 nationwide studies on surgically treated patients with INAAs in Sweden, between 1994 - 2016. Patients were grouped and analyzed according to culture results: 1) Staphylococcus aureus, 2) Streptococcus species (sp.), 3) Salmonella sp., 4) Enterococcus sp., 5) Gram-negative intestinal bacteria, 6) Other sp. (all other species found in culture), and 7) Negative cultures. Results: A sum of 182 patients were included, mean age 71 years (standard deviation; SD: 8.9). The median follow-up was 50.3 months (range 0 - 360). 128 (70.3%) patients had positive blood and/or tissue culture; Staphylococcus aureus n = 38 (20.9%), Streptococcus sp. n = 37 (20.3%), Salmonella sp. n = 19 (10.4%), Enterococcus sp. n = 16 (8.8%), Gram-negative intestinal bacteria n = 6, (3.3%), Other sp. n = 12 (6.6%) and Negative cultures n = 54 (29.7%). The estimated survival for the largest groups at 2-years after surgery was: Staphylococcus aureus 62% (95% Confidence interval 53.9 - 70.1), Streptococcus sp. 74.7% (67.4 - 82.0), Salmonella sp. 73.7% (63.6 - 83.8), Enterococcus sp. 61.9% (49.6 - 74.2), and Negative cultures 89.8% (85.5 - 94.1), P =.051. There were 37 IRCs (20.3%), and 19 (51.4%) were fatal, the frequency was insignificant between the groups. The majority of IRCs, 30/37 (81%), developed during the first postoperative year. Conclusion: In this assessment of microbiological findings of INAAs in Sweden, 50% of the pathogens were Staphylococcus aureus, Streptococcus sp., or Salmonella sp.. The overall 20%-frequency of IRCs, and its association with high mortality, motivates long-term antibiotic treatment regardless of microbial findings.
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| 18. |
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| 19. |
- Wahlgren, Glenn, et al.
(författare)
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The Bismuth Abundance in the HGMN Stars chi Lupi and HR 7775 and Improved Atomic Data for Selected Transitions of BI I, BI II, and BI III
- 2001
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 551:1, s. 520-535
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Tidskriftsartikel (refereegranskat)abstract
- High-resolution spectra of the chemically peculiar HgMn stars chi Lupiand HR 7775, obtained with the Hubble Space Telescope/Goddard HighResolution Spectrograph, are investigated for their abundance of bismuthby comparison with LTE synthetic spectrum modeling. HR 7775, previouslyknown from International Ultraviolet Explorer spectra to display stronglines of Bi II, is determined to have bismuth present at an enhancementlevel of nearly 5 orders of magnitude from the lines Bi IIlambdalambda1436, 1902 and Bi III lambda1423. The bismuthenhancement for chi Lupi is found to be near a level of 1.5 dex, andan ionization anomaly between Bi+ and Bi++ isapparent. HR 7775 abundance enhancements of the heavy elements platinum,[Pt/H]=4.7 dex, and gold, [Au/H]=3.8 dex, have also been determined. Newlaboratory measurements for wavelengths and hyperfine structure patternsof Bi I/Bi II/Bi III lines are presented, as well as the results ofcalculations for hyperfine structure constants and oscillator strengthsfor selected lines of Bi II and Bi III. Based on observations with theNASA/ESA Hubble Space Telescope, obtained at the Space Telescope ScienceInstitute, which is operated by the Association of Universities forResearch in Astronomy, Inc., under NASA contract NAS5-26555.
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| 20. |
- Currie, Michael J., et al.
(författare)
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Structural and biophysical analysis of a Haemophilus influenzae tripartite ATP-independent periplasmic (TRAP) transporter
- 2024
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Ingår i: ELIFE. - 2050-084X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Tripartite ATP-independent periplasmic (TRAP) transporters are secondary-active transporters that receive their substrates via a soluble-binding protein to move bioorganic acids across bacterial or archaeal cell membranes. Recent cryo-electron microscopy (cryo-EM) structures of TRAP transporters provide a broad framework to understand how they work, but the mechanistic details of transport are not yet defined. Here we report the cryo-EM structure of the Haemophilus influenzae N-acetylneuraminate TRAP transporter (HiSiaQM) at 2.99 & Aring; resolution (extending to 2.2 & Aring; at the core), revealing new features. The improved resolution (the previous HiSiaQM structure is 4.7 & Aring; resolution) permits accurate assignment of two Na+ sites and the architecture of the substrate-binding site, consistent with mutagenic and functional data. Moreover, rather than a monomer, the HiSiaQM structure is a homodimer. We observe lipids at the dimer interface, as well as a lipid trapped within the fusion that links the SiaQ and SiaM subunits. We show that the affinity (K-D) for the complex between the soluble HiSiaP protein and HiSiaQM is in the micromolar range and that a related SiaP can bind HiSiaQM. This work provides key data that enhances our understanding of the 'elevator-with-an-operator' mechanism of TRAP transporters.
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| 21. |
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| 22. |
- Escudero-Martnez, I, et al.
(författare)
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Association of cholesterol levels with hemorrhagic transformation and cerebral edema after reperfusion therapies
- 2023
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Ingår i: European stroke journal. - : SAGE Publications. - 2396-9881 .- 2396-9873. ; 8:1, s. 294-300
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Tidskriftsartikel (refereegranskat)abstract
- The association between cholesterol levels and cerebral edema (CED) or hemorrhagic transformation (HT) as an expressions of blood-brain barrier (BBB) dysfunction after ischemic stroke is not well established. The aim of this study is to determine the association of total cholesterol (TC) levels with the incidence of HT and CED after reperfusion therapies. Methods: We analyzed SITS Thrombolysis and Thrombectomy Registry data from January 2011 to December 2017. We identified patients with data on TC levels at baseline. TC values were categorized in three groups (reference group ⩾200 mg/dl). The two primary outcomes were any parenchymal hemorrhage (PH) and moderate to severe CED on follow up imaging. Secondary outcomes included death and functional independence (mRS 0–2) at 3 months. Multivariable logistic regression analysis adjusted for baseline factors including statin pretreatment was used to assess the association between TC levels and outcomes. Results: Of 35,314 patients with available information on TC levels at baseline, 3372 (9.5%) presented with TC levels ⩽130 mg/dl, 8203 (23.2%) with TC 130–200 mg/dl and 23,739 (67.3%) with TC ⩾ 200 mg/dl. In the adjusted analyses, TC level as continuous variable was inversely associated with moderate to severe CED (OR 0.99, 95% CI 0.99–1.00, p = 0.025) and as categorical variable lower TC levels were associated with a higher risk of moderate to severe CED (aOR 1.24, 95% CI 1.10–1.40, p = 0.003). TC levels were not associated with any PH, functional independence, and mortality at 3 months. Conclusions: Our findings indicate an independent association between low levels of TC and higher odds of moderate/severe CED. Further studies are needed to confirm these findings.
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| 23. |
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| 24. |
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| 25. |
- Johansson, C., et al.
(författare)
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Atopy patch test reactions to Malassezia allergens differentiate subgroups of atopic dermatitis patients.
- 2003
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Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 1365-2133 .- 0007-0963. ; 148:3, s. 479-488
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Tidskriftsartikel (refereegranskat)abstract
- Background The yeast Malassezia is considered to be one of the factors that can contribute to atopic dermatitis (AD). Objectives To investigate the reactivity to Malassezia allergens, measured as specific serum IgE, positive skin prick test and positive atopy patch test (APT), in adult patients with AD. Methods In total, 132 adult patients with AD, 14 with seborrhoeic dermatitis (SD) and 33 healthy controls were investigated for their reactions to M. sympodialis extract and three recombinant Malassezia allergens (rMal s 1, rMal s 5 and rMal s 6). Results Sixty-seven per cent of the AD patients, but only one of the SD patients and none of the healthy controls, showed a positive reaction to at least one of the Malassezia allergens (extract and/or recombinant allergens) in at least one of the tests. The levels of M. sympodialis-specific IgE in serum correlated with the total serum IgE levels. Elevated serum levels of M. sympodialis-specific IgE were found in 55% and positive APT reactions in 41% of the AD patients with head and neck dermatitis. A relatively high proportion of patients without head and neck dermatitis and patients with low total serum IgE levels had a positive APT for M. sympodialis, despite lower proportions of individuals with M. sympodialis-specific IgE among these groups of patients. Conclusions These results support that Malassezia can play a role in eliciting and maintaining eczema in patients with AD. The addition of an APT to the test battery used in this study reveals a previously overlooked impact of Malassezia hypersensitivity in certain subgroups of AD patients.
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| 26. |
- Johansson, Linda C, 1983, et al.
(författare)
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Structure of a photosynthetic reaction centre determined by serial femtosecond crystallography.
- 2013
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Serial femtosecond crystallography is an X-ray free-electron-laser-based method with considerable potential to have an impact on challenging problems in structural biology. Here we present X-ray diffraction data recorded from microcrystals of the Blastochloris viridis photosynthetic reaction centre to 2.8Å resolution and determine its serial femtosecond crystallography structure to 3.5Å resolution. Although every microcrystal is exposed to a dose of 33MGy, no signs of X-ray-induced radiation damage are visible in this integral membrane protein structure.
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| 27. |
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| 28. |
- Karlsson, Camilla A-C, et al.
(författare)
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Detergent Induced Removal of b-Lactoglobulin from Stainless Steel Surfaces at Influenced by Surface Pretreatment
- 1999
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 1095-7103 .- 0021-9797. ; 220, s. 471-473
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Tidskriftsartikel (refereegranskat)abstract
- The adsorption of β-lactoglobulin to stainless steel and its subsequent removal were followed using in situ null ellipsometry. The influence of the surface pretreatment on the protein removal by the surfactant SDS and by sodium hydroxide was studied. All surfaces were precleaned in strongly alkaline solution. Some surfaces received no further pretreatment, while others were either passivated in nitric acid or plasma-cleaned prior to experiments. Stainless steel surfaces subjected to different surface pretreatments showed considerable differences in cleaning behavior. Cleaning, using NaOH, of surfaces which had been precleaned with alkali only or with plasma resulted in practically complete β-lactoglobulin removal. In contrast, appreciable amounts of protein remained on passivated stainless steel. Protein removal by SDS was limited and comparable for all three surface pretreatments investigated. Only minor effects on the protein adsorption tendency were observed. The amounts of β-lactoglobulin adsorbed tended to be somewhat lower on the passivated surfaces.
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| 29. |
- Karlsson, Camilla A.C., et al.
(författare)
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Non-invasive monitoring of protein adsorption and removal in a turbulent flow cell
- 2001
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Ingår i: Colloids and Surfaces B: Biointerfaces. - 0927-7765. ; 20:1, s. 9-25
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Tidskriftsartikel (refereegranskat)abstract
- A flow cell was designed for continuous non-invasive measurements of macromolecular adsorption and removal under well-defined flow conditions. The adsorption of the protein β-lactoglobulin to stainless steel surfaces and its subsequent detergent-induced removal were followed in the flow cell using in situ ellipsometry under both laminar and turbulent conditions. Factors varied include the cleaning agent type and concentration, the flow rate and the protein concentration. In addition, the experiments studying different cleaning agents were repeated in a stirred cuvette system employed in previous work. The ellipsometer as well as the experimental set-ups are described, with particular emphasis on the flow cell design. Evaluation of the results is done by comparing the amounts of protein adsorbed from solution, the initial adsorption rates, the amounts removed in water or detergent and the residual amounts after cleaning. The results are discussed in terms of β-lactoglobulin unfolding, preferential adsorption, different states of adsorbed molecules, additional physicochemical aspects and hydrodynamic characteristics. (C) 2001 Elsevier Science B.V.
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| 30. |
- Karlsson, Camilla A-C, et al.
(författare)
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Some surface-related aspects of the cleaning of new and reused stainless-steel surfaces fouled by protein
- 1998
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Ingår i: International Dairy Journal. - 0958-6946. ; 8:10, s. 925-933
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Tidskriftsartikel (refereegranskat)abstract
- The adsorption of β-lactoglobulin to stainless steel and its subsequent alkali-induced removal were followed using ellipsometry. New steel samples differing in bulk composition, surface finish or chemical pretreatment were used. All surfaces were precleaned in strongly alkaline solution, and some were subsequently passivated in nitric acid. Furthermore, on surfaces differing in pretreatment measurements were performed during repeated fouling and cleaning cycles. No correlation was found between the bulk composition or the surface finish and the fouling tendency or the cleanability. However, striking differences in cleanability between stainless-steel surfaces subjected to different chemical pretreatments were evident, particularly at low temperature. Still, only minor effects on the fouling tendency were observed. When subjecting surfaces to repeated fouling and cleaning without renewed pretreatment, the differences in cleaning performance decreased but were still significant. While the cleanability of non-passivated surfaces appeared to decrease somewhat when reused, changes seemed smaller for passivated surfaces.
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| 31. |
- Karlsson, Camilla A-C, et al.
(författare)
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Time and temperature aspects of β-lactoglobulin removal from methylated silica surfaces by sodium dodecyl sulphate
- 1996
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Ingår i: Colloids and Surfaces B: Biointerfaces. - : Elsevier BV. - 0927-7765. ; 6:4, s. 317-328
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Tidskriftsartikel (refereegranskat)abstract
- The adsorption of β-lactoglobulin onto methylated silica surfaces and the subsequent protein removal by the anionic surfactant sodium dodecyl sulphate (SDS) were followed using in-situ ellipsometry. Experiments were performed at pH 6.0 in phosphate-buffered saline solution. Parameters varied include temperature, length of time for protein adsorption from solution and surface residence time of β-lactoglobulin. The temperature was kept constant throughout a trial, and the majority of experiments were carried out at a few degrees below the protein denaturation temperature as reported from differential scanning calorimetry studies. β-Lactoglobulin adsorption at high temperatures resulted in aggregation at the surface after a lag phase of several minutes. Varying the protein adsorption time and thus the amount adsorbed while keeping the protein surface residence time fixed did not seem to affect the amount desorbed upon rinsing or the amount eluted by surfactant. For short β-lactoglobulin adsorption times, the adsorbed amounts were comparable at all temperatures studied. The temperature hardly affected the amount desorbed during rinsing, but did however have a pronounced influence on the protein removed by surfactant. Up to around 60°C practically all β-lactoglobulin was eluted by the SDS. The fraction removed then decreased with temperature, with a sharp drop between 70 and 73°C, and a further decline at higher levels. SDS was seen to be highly inefficient at removing β-lactoglobulin adsorbed at temperatures above 70°C. The trend observed is attributed to temperature-dependent changes in the protein resident on the surface. The β-lactoglobulin surface residence time was seen to significantly affect the elutability. At short residence times the removal efficiency was comparably high, but decreased with time. However, no significant difference could be detected between two sufficiently long residence times. The behaviour is consistent with the assumption of multiple states of adsorbed proteins, together with slow conformational changes in the adsorbed protein layer.
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| 32. |
- Karlsson, Camilla A-C, et al.
(författare)
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β-Lactoglobulin fouling and its removal upon rinsing and by SDS as influenced by surface characteristics, temperature and adsorption time
- 1996
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Ingår i: Journal of Food Engineering. - 0260-8774. ; 30:1-2, s. 43-60
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Tidskriftsartikel (refereegranskat)abstract
- The extensive fouling common in the food industry puts high demands on equipment cleaning. The adsorption of β-lactoglobulin and its removal by the anionic surfactant sodium dodecyl sulphate (SDS) were followed at pH 6.0 using in situ ellipsometry. Hydrophilic chromium oxide and stainless steel together with hydrophobic methylated silica were studied at different temperatures. Differences between chromium oxide and steel were small, while hydrophobic silica showed significantly different initial adsorption kinetics and adsorbed amounts. Also, the temperature-dependence of the amount desorbed upon rinsing as well as of the overall cleanability differed greatly. At around the β-lactoglobulin denaturation temperature, multilayer build-up at the surface was seen, and the cleanability was very low. Of two protein adsorption times employed, the longer resulted, for metal oxide surfaces, in less desorption during rinsing.
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| 33. |
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| 34. |
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| 35. |
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| 36. |
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| 37. |
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| 38. |
- Montan, C., et al.
(författare)
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Massive Blood Transfusion in Patients with Ruptured Abdominal Aortic Aneurysm
- 2016
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884. ; 52:5, s. 597-603
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The aim was to study blood transfusions and blood product ratios in massively transfused patients treated for ruptured abdominal aortic aneurysms (rAAAs). Methods This was a registry based cohort study of rAAA patients repaired at three major vascular centres between 2008 and 2013. Data were collected from the Swedish Vascular Registry, hospitals medical records, and local transfusion registries. The transfusion data were analysed for the first 24 h of treatment. Massive transfusion (MT) was defined as 4 or more units of red blood cell (RBC) transfused within 1 h, or 10 or more RBC units within 24 h. Logistic regression was used to calculate the odds ratio of 30 day mortality associated with the ratios of blood products and timing of first units of platelets (PLTs) and fresh frozen plasma (FFP) transfused. Results Three hundred sixty nine rAAA patients were included: 80% men; 173 endovascular aneurysm repairs (EVARs) and 196 open repairs (ORs) with median RBC transfusion 8 units (Q1–Q3, 4–14) and 14 units (Q1–Q3, 8–28), respectively. A total of 261 (71%) patients required MT. EVAR patients with MT (n = 96) required less transfusion than OR patients (n = 165): median RBC 10 units (Q1–Q3, 6–16.5) vs. 15 units (Q1–Q3, 9–26) (p = .002), FFP 6 units (Q1–Q3, 2–14.5) vs. 13 units (Q1–Q3, 7–24) (p < .001), and PLT 0 units (Q1–Q3, 0–2) vs. 2 units (Q1–Q3, 0–4) (p = .01). Median blood product ratios in MT patients were FFP/RBC (EVAR group 0.59 [0.33–0.86], OR group 0.84 [0.67–1.2]; p < .001], and PLT/RBC (EVAR 0 [0–0.17], OR 0.12 (0–0.18); p < .001]. In patients repaired by OR a FFP/RBC ratio close to 1 was associated with reduced 30 day mortality (p = .003). The median PLT/RBC ratio was higher during the later part of the study period (p < .001, median test), whereas there was no significant difference in median FFP/RBC ratio (p = .101, median test). Conclusion The majority of rAAA patients undergoing EVAR required MT. EVAR patients treated with MT had lower FFP/RBC and PLT/RBC ratios than OR patients with MT. The mortality risk was lower with FFP/RBC ratio close to 1:1 in open repaired patients requiring MT. The 24 h PLT/RBC ratio increased over the study period.
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| 39. |
- Montan, C., et al.
(författare)
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Perioperative Haemorrhage in Endovascular Abdominal Aneurysm Repair Affects Outcome
- 2013
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1532-2165 .- 1078-5884. ; 46:1, s. 87-92
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study aimed to evaluate the outcome and predisposing factors related to perioperative bleeding in patients treated with endovascular aneurysm repair (VAR) for ruptured and non-ruptured abdominal aortic aneurysm (AAA). Design: This was a retrospective cohort study. Methods: A total of 525 consecutive patients (73% elective) with AAA underwent EVAR at two vascular centres from 2008 to 2011. From registry data perioperative bleeding was analysed in relation to outcome and preoperative data. Results: A total of 453 (86%) patients presented with a perioperative bleeding <1000 ml, 42 (8%) patients 1000-1999 ml, 19 (4%) patients 2000-5000 ml and 11 (2%) >5000 ml. Other than ruptured AAA (n = 90), no preoperative risk factors for increased perioperative bleeding were found. Open femoral artery access (n = 101), branched (n = 18) and uni-iliacal endografts (n = 18) and introducer size were associated with increased perioperative bleeding (P < 0.001). In multivariable logistic regression only rupture and perioperative bleeding >2000 ml were significantly related to 30-day mortality (odds ratio 10.6 (range 3.8-29.6) and 13.4 (range 4.8-37.4), respectively). Postoperative renal failure, multi-organ failure, >5 days at intensive care unit, bowel ischaemia and abdominal compartments syndrome were significantly related to perioperative bleeding >2000 ml (P < 0.001). Conclusion: Large perioperative bleeding during EVAR is a clinical problem that affects outcome. About 10% of elective AAA patients and 34% of patients with ruptured AAA, undergoing EVAR, present a perioperative blood loss exceeding 1 I. In our study, a perioperative blood loss exceeding 2 I was independently associated with increased mortality and morbidity in both acute and elective AAA patients. Open femoral access, branched EVAR and larger diameter introducers were associated with increased perioperative blood loss. Ethical application: 2011/664-31/3 (approved). (C) 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
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| 40. |
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| 41. |
- North, Rachel A, et al.
(författare)
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"Just a spoonful of sugar...": import of sialic acid across bacterial cell membranes
- 2018
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Ingår i: Biophysical reviews. - : Springer Science and Business Media LLC. - 1867-2450 .- 1867-2469. ; 10:2, s. 219-227
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Forskningsöversikt (refereegranskat)abstract
- Eukaryotic cell surfaces are decorated with a complex array of glycoconjugates that are usually capped with sialic acids, a large family of over 50 structurally distinct nine-carbon amino sugars, the most common member of which is N-acetylneuraminic acid. Once made available through the action of neuraminidases, bacterial pathogens and commensals utilise host-derived sialic acid by degrading it for energy or repurposing the sialic acid onto their own cell surface to camouflage the bacterium from the immune system. A functional sialic acid transporter has been shown to be essential for the uptake of sialic acid in a range of human bacterial pathogens and important for host colonisation and persistence. Here, we review the state-of-play in the field with respect to the molecular mechanisms by which these bio-nanomachines transport sialic acids across bacterial cell membranes.
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| 42. |
- Ringleb, PA, et al.
(författare)
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Guidelines for management of ischaemic stroke and transient ischaemic attack 2008
- 2008
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Ingår i: Cerebrovascular diseases (Basel, Switzerland). - : S. Karger AG. - 1421-9786 .- 1015-9770. ; 25:5, s. 457-507
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Tidskriftsartikel (refereegranskat)abstract
- This article represents the update of the European Stroke Initiative Recommendations for Stroke Management. These guidelines cover both ischaemic stroke and transient ischaemic attacks, which are now considered to be a single entity. The article covers referral and emergency management, Stroke Unit service, diagnostics, primary and secondary prevention, general stroke treatment, specific treatment including acute management, management of complications, and rehabilitation.
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| 43. |
- Sandström Falk, Mari Helen, 1958, et al.
(författare)
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The prevalence of Malassezia yeasts in patients with atopic dermatitis, seborrhoeic dermatitis and healthy controls
- 2005
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Ingår i: Acta Derm Venereol. - : Medical Journals Sweden AB. ; 85:1, s. 17-23
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Tidskriftsartikel (refereegranskat)abstract
- Cultures for Malassezia yeasts were taken from both normal-looking skin and lesional skin in 124 patients with atopic dermatitis, 16 patients with seborrhoeic dermatitis and from normal skin of 31 healthy controls. Positive Malassezia growth was found in fewer patients with atopic dermatitis (56%) than in patients with seborrhoeic dermatitis (88%) or in healthy controls (84%, p<0.01). In the patients with atopic dermatitis, fewer positive cultures were found in lesional (28%) than in non-lesional skin (44%, p<0.05), while positive cultures were found in 75% of both lesional and non-lesional skin of patients with seborrhoeic dermatitis (not significant). M. sympodialis dominated in patients with atopic dermatitis (46%) and in healthy controls (69%). In patients with seborrhoeic dermatitis both M. sympodialis and M. obtusa were cultured in 43%. A Malassezia species extract mixture would increase the possibility of detecting IgE sensitization to Malassezia in patients with atopic dermatitis.
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| 44. |
- Santonocito, M., et al.
(författare)
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Molecular characterization of exosomes and their microRNA cargo in human follicular fluid: bioinformatic analysis reveals that exosomal microRNAs control pathways involved in follicular maturation
- 2014
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Ingår i: Fertility and Sterility. - : Elsevier BV. - 0015-0282. ; 102:6
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To characterize well-represented microRNAs in human follicular fluid (FF) and to ascertain whether they are cargo of FF exosomes and whether they are involved in the regulation of follicle maturation. Design: FF exosomes were characterized by nanosight, flow cytometry, and exosome-specific surface markers. Expression microRNA profiles from total and exosomal FF were compared with those from plasma of the same women. Patient(s): Fifteen healthy women who had undergone intracytoplasmic sperm injection. Main Outcome Measure(s): TaqMan low-density array to investigate the expression profile of 384 microRNAs; DataAssist and geNorm for endogenous control identification; significance analysis of microarrays to identify differentially expressed microRNAs; nanosight, flow-cytometry, and bioanalyzer for exosome characterization; bioinformatic tools for microRNAs target prediction, gene ontology, and pathway analysis. Result(s): We identified 37 microRNAs upregulated in FF as compared with plasma from the same women. Thirty-two were carried by microvesicles that showed the well-characterized exosomal markers CD63 and CD81. These FF microRNAs are involved in critically important pathways for follicle growth and oocyte maturation. Specifically, nine of them target and negatively regulate mRNAs expressed in the follicular microenvironment encoding inhibitors of follicle maturation and meiosis resumption. Conclusion(s): This study identified a series of exosomal microRNAs that are highly represented in human FF and are involved in follicular maturation. They could represent noninvasive biomarkers of oocyte quality in assisted reproductive technology. (C) 2014 by American Society for Reproductive Medicine.
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| 45. |
- Sikstrom, C. M, et al.
(författare)
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New Zr II oscillator strengths and the zirconium conflict in the HgMn star chi Lupi
- 1999
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Ingår i: Astronomy & Astrophysics. - 0004-6361. ; 343:1, s. 297-302
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Tidskriftsartikel (refereegranskat)abstract
- Lifetimes on the sub-nanosecond scale for the levels v(2)D(3/2), v(2)F(3/2) and v(2)F(5/2) in the 4d5s5p configuration in Zr II have been measured, using the method of laser-induced fluorescence. Combined with branching fractions obtained with the Lund Ultraviolet (UV) Fourier Transform Spectrometer (FTS), experimental oscillator strengths have been derived. From Hubble Space Telescope/Goddard High-Resolution Spectrograph spectra, the zirconium abundance in the HgMn star chi Lupi has been determined from Zr II and Zr III lines. More than an order of magnitude difference in the Zr II abundance has been derived from these ionization stages. The difference is much too large to be explained by uncertainties in the oscillator strengths. Possible explanations of this difference have to be found in the stellar models, such as the influence of non-LTE or diffusion.
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| 46. |
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| 47. |
- Stea, T. H., et al.
(författare)
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Mapping the Concept, Content, and Outcome of Family-Based Outdoor Therapy for Children and Adolescents with Mental Health Problems : A Scoping Review
- 2022
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 19:10
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Forskningsöversikt (refereegranskat)abstract
- Outdoor therapy and family-based therapy are suggested to be promising interventions for the treatment of mental health problems. The aim of the present scoping review was to systematically map the concept, content, and outcome of combining family-and outdoor-based therapy for children and adolescents with mental health problems. The Joanna Briggs Institute methodology and PRISMA guidelines were applied. Eligible qualitative and quantitative studies were screened, included, and extracted for data. Seven studies were included. Findings from these studies indicated that family-based outdoor therapy programs have a positive impact on family-and peer relationships, adolescent behavior, mental health, self-perceptions (self-concept), school success, social engagement, and delinquency rates. However, participant characteristics, study design, and content and mode of delivery of the interventions varied substantially, hence preventing detailed comparison of outcomes across studies. In addition, most of the studies included few participants and lacked population diversity and comparable control groups. Although important ethical concerns were raised, such as non-voluntary participation in some of the programs, there was a lack of reporting on safety. This review indicates that a combination of family-and outdoor-based therapy may benefit mental health among children and adolescents, but due to the limited number of studies eligible for inclusion and high levels of heterogeneity, it was difficult to draw firm conclusions. Thus, future theory-based studies using robust designs are warranted.
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| 48. |
- van Baar, A. C. G., et al.
(författare)
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Duodenal L cell density correlates with features of metabolic syndrome and plasma metabolites
- 2018
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Ingår i: Endocrine Connections. - : Bioscientifica. - 2049-3614. ; 7:5, s. 673-680
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Tidskriftsartikel (refereegranskat)abstract
- Background: Enteroendocrine cells are essential for the regulation of glucose metabolism, but it is unknown whether they are associated with clinical features of metabolic syndrome (MetS) and fasting plasma metabolites. Objective: We aimed to identify fasting plasma metabolites that associate with duodenal L cell, K cell and delta cell densities in subjects with MetS with ranging levels of insulin resistance. Research design and methods: In this cross-sectional study, we evaluated L, K and delta cell density in duodenal biopsies from treatment-naive males with MetS using machine-learning methodology. Results: We identified specific clinical biomarkers and plasma metabolites associated with L cell and delta cell density. L cell density was associated with increased plasma metabolite levels including symmetrical dimethylarginine, 3-aminoisobutyric acid, kynurenine and glycine. In turn, these L cell-linked fasting plasma metabolites correlated with clinical features of MetS. Conclusions: Our results indicate a link between duodenal L cells, plasma metabolites and clinical characteristics of MetS. We conclude that duodenal L cells associate with plasma metabolites that have been implicated in human glucose metabolism homeostasis. Disentangling the causal relation between L cells and these metabolites might help to improve the (small intestinal-driven) pathophysiology behind insulin resistance in human obesity.
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| 50. |
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