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Sökning: WFRF:(Wahlgren T)

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1.
  • Abdo, A. A., et al. (författare)
  • Gamma-ray emission concurrent with the nova in the symbiotic binary V407 cygni
  • 2010
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 329:5993, s. 817-821
  • 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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  • Ederle, Joerg, et al. (författare)
  • 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
  • Ingår i: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
  • 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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  • Chalmers, J. R., et al. (författare)
  • Report from the fourth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative)
  • 2016
  • Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 175:1, s. 69-79
  • 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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  • Lebzelter, T., et al. (författare)
  • Comparative modelling of the spectra of cool giants
  • 2012
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 547, s. A108-
  • 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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  • Bergqvist, D, et al. (författare)
  • Haverikommission granskade karotiskirurgins komplikationer. Hälften kunde förklaras med misstag eller tveksamma indikationer
  • 2000
  • Ingår i: Läkartidningen. - 0023-7205. ; 97:14, s. 1673-1676
  • Tidskriftsartikel (refereegranskat)abstract
    • As carotid endarterectomy is a prophylactic procedure, it would seem particularly important to analyze complications with an aim to avoiding them. All carotid endarterectomies in Sweden are registered, and all serious complications (death and permanent neurological deficit) are analyzed in detail, classified and discussed within the profession. During the period 1994-1996 the frequency was 4.3 percent (technical causes in 17 percent, contraindications in 8 percent and dubious indications in 21 percent, but correct indication and surgery in 54 percent). Thus, even when conditions are optimal there is a certain price to pay for the prevention of ischemic stroke.
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11.
  • Carrillo, M., et al. (författare)
  • High-resolution crystal structures of transient intermediates in the phytochrome photocycle
  • 2021
  • Ingår i: Structure. - : Elsevier BV. - 0969-2126. ; 29:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Phytochromes are red/far-red light photoreceptors in bacteria to plants, which elicit a variety of important physiological responses. They display a reversible photocycle between the resting Pr state and the light-activated Pfr state. Light signals are transduced as structural change through the entire protein to modulate its activity. It is unknown how the Pr-to-Pfr interconversion occurs, as the structure of intermediates remains notoriously elusive. Here, we present short-lived crystal structures of the photosensory core modules of the bacteriophytochrome from myxobacterium Stigmatella aurantiaca captured by an X-ray free electron laser 5 ns and 33 ms after light illumination of the Pr state. We observe large structural displacements of the covalently bound bilin chromophore, which trigger a bifurcated signaling pathway that extends through the entire protein. The snapshots show with atomic precision how the signal progresses from the chromophore, explaining how plants, bacteria, and fungi sense red light.
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  • Kull, T, et al. (författare)
  • Effect of surface properties and added electrolyte on the structure of β-casein layers adsorbed at the solid/aqueous interface
  • 1997
  • Ingår i: Langmuir. - 0743-7463 .- 1520-5827. ; 13, s. 5141-5147
  • Tidskriftsartikel (refereegranskat)abstract
    • The adsorption of -casein at hydrophobic and hydrophilic silica surfaces has been studied by time-resolved ellipsometry. Marked differences in, e.g., adsorption kinetics and plateau adsorption coverage, were observed on the two types of surfaces. The miscellaneous adsorption mechanisms at the two surfaces resulted in different structures of the adsorbed layers as evident from the thicknesses and protein densities measured on the two substrates as well as the effect on the adsorbed layer properties of a subsequently added specific proteolytic enzyme, endoproteinase Asp-N. At the hydrophobic surface, the adsorption is fast and the surface is saturated within a relatively short period. The addition of endoproteinase Asp-N reduces the surface excess and the thickness by 24 and 45%, respectively. This corresponds to cleavage at amino acid residues 43 and/or 47 in the hydrophilic portion of the protein. Adsorption from solutions containing added electrolyte leads to significant increase of the surface excess. However, no significant change was observed in the ellipsometric layer thickness. At constant ionic strength, the surface excess increased in the order NaCl < MgCl2 < CaCl2. From the experimental evidence, it was concluded that the adsorbed layer structure at the hydrophobic surface can be described as a monolayer with an inner dense region comprising the relatively large hydrophobic portions of the protein molecules and an outer region of the highly charged N-terminal portions protruding into the aqueous phase. The adsorption kinetics at the hydrophilic silica surface, although initially the same as on the hydrophobic surface, was found to be much slower and plateau surface excess values were not reached even after 2 h of adsorption. This suggests that substantial rearrangements of the protein molecules take place within the adsorbed layer during the adsorption process. Although the maximum surface excess at the hydrophilic surface of 4.3 mg m-2 is higher than the value of 2.8 mg m-2 measured at the hydrophobic surface, the thickness is slightly smaller, i.e., 60 Å and 66 Å, respectively. Hence, the protein adopt a more compact structure at the hydrophilic surface, at least in the inner part of the adsorbed layer. The different structure at the hydrophilic surface was confirmed by the larger reduction of the surface excess and layer thickness associated with the addition of endoproteinase Asp-N, leaving a very thin compact layer at the surface.
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  • Sorelius, Karl, et al. (författare)
  • The Microbiology of Infective Native Aortic Aneurysms in a Population-Based Setting
  • 2022
  • Ingår i: Annals of Vascular Surgery. - : Elsevier. - 0890-5096 .- 1615-5947. ; 78, s. 112-122
  • 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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  • Wahlgren, N G, et al. (författare)
  • Multidisciplinärt samarbete bakom kvalitetsregister för karotiskirurgi. God täckningsgrad under de första två verksamhetsåren
  • 2000
  • Ingår i: Läkartidningen. - 0023-7205. ; 97:14, s. 1678-1678
  • Tidskriftsartikel (refereegranskat)abstract
    • Carotid surgery prevents recurrent stroke in patients with symptomatic tight stenosis of the carotid artery. The Swedish Carotid Surgery Monitoring Registry seeks to promote selection of patients with significant spontaneous risk for recurrent stroke, with an eye toward expediting evaluation and minimizing surgical complications. To this end, professionals at participating hospitals are informed about their own patient selection and surgery risk in comparison with those in the country as a whole and with set targets. We report the results from the first two years, during which it is estimated that more than half of all patients eligible for carotid surgery in Sweden were included in the registry. Although almost all patients had recent onset of relevant neurological symptoms, less than 60% had a documented tight (80-99% occlusion) stenosis. While the final decision to operate a patient was made within 4 weeks of onset of symptoms for only 18% of the patients the first year, this proportion increased to 33% in the following year. The total incidence of surgery related stroke, myocardial infarct and death was 7.7%, while the incidence of severe stroke, myocardial infarct and death was 3.0%.
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18.
  • Wahlgren, N., et al. (författare)
  • Mechanical thrombectomy in acute ischemic stroke: Consensus statement by ESO-Karolinska Stroke Update 2014/2015, supported by ESO, ESMINT, ESNR and EAN
  • 2016
  • Ingår i: International Journal of Stroke. - : SAGE Publications. - 1747-4930 .- 1747-4949. ; 11:1, s. 134-147
  • Tidskriftsartikel (refereegranskat)abstract
    • The original version of this consensus statement on mechanical thrombectomy was approved at the European Stroke Organisation (ESO)-Karolinska Stroke Update conference in Stockholm, 16-18 November 2014. The statement has later, during 2015, been updated with new clinical trials data in accordance with a decision made at the conference. Revisions have been made at a face-to-face meeting during the ESO Winter School in Berne in February, through email exchanges and the final version has then been approved by each society. The recommendations are identical to the original version with evidence level upgraded by 20 February 2015 and confirmed by 15 May 2015. The purpose of the ESO-Karolinska Stroke Update meetings is to provide updates on recent stroke therapy research and to discuss how the results may be implemented into clinical routine. Selected topics are discussed at consensus sessions, for which a consensus statement is prepared and discussed by the participants at the meeting. The statements are advisory to the ESO guidelines committee. This consensus statement includes recommendations on mechanical thrombectomy after acute stroke. The statement is supported by ESO, European Society of Minimally Invasive Neurological Therapy (ESMINT), European Society of Neuroradiology (ESNR), and European Academy of Neurology (EAN).
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  • Ahmed, N, et al. (författare)
  • The SITS-UTMOST: A registry-based prospective study in Europe investigating the impact of regulatory approval of intravenous Actilyse in the extended time window (3-4.5 h) in acute ischaemic stroke
  • 2016
  • Ingår i: European stroke journal. - : SAGE Publications. - 2396-9881 .- 2396-9873. ; 1:3, s. 213-221
  • Tidskriftsartikel (refereegranskat)abstract
    • The SITS-UTMOST (Safe Implementation of Thrombolysis in Upper Time window Monitoring Study) was a registry-based prospective study of intravenous alteplase used in the extended time window (3–4.5 h) in acute ischaemic stroke to evaluate the impact of the approval of the extended time window on routine clinical practice. Patients and methods Inclusion of at least 1000 patients treated within 3–4.5 h according to the licensed criteria and actively registered in the SITS-International Stroke Thrombolysis Registry was planned. Prospective data collection started 2 May 2012 and ended 2 November 2014. A historical cohort was identified for 2 years preceding May 2012. Clinical management and outcome were contrasted between patients treated within 3 h versus 3–4.5 h in the prospective cohort and between historical and prospective cohorts for the 3 h time window. Outcomes were functional independency (modified Rankin scale, mRS) 0–2, favourable outcome (mRS 0–1), and death at 3 months and symptomatic intracerebral haemorrhage (SICH) per SITS. Results 4157 patients from 81 centres in 12 EU countries were entered prospectively ( N = 1118 in the 3–4.5 h, N = 3039 in the 0–3 h time window) and 3454 retrospective patients in the 0–3 h time window who met the marketing approval conditions. In the prospective cohort, median arrival to treatment time was longer in the 3–4.5 h than 3 h window (79 vs. 55 min). Within the 3 h time window, treatment delays were shorter for prospective than historical patients (55 vs. 63). There was no significant difference between the 3–4.5 h versus 3 h prospective cohort with regard to percentage of reported SICH (1.6 vs. 1.7), death (11.6 vs. 11.1), functional independency (66 vs. 65) at 3 months or favourable outcome (51 vs. 50). Discussion Main weakness is the observational design of the study. Conclusion This study neither identified negative impact on treatment delay, nor on outcome, following extension of the approved time window to 4.5 h for use of alteplase in stroke.
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  • Al-Rukn, S, et al. (författare)
  • Stroke in the Middle-East and North Africa: A 2-year prospective observational study of intravenous thrombolysis treatment in the region. Results from the SITS-MENA Registry
  • 2020
  • Ingår i: International journal of stroke : official journal of the International Stroke Society. - : SAGE Publications. - 1747-4949. ; 15:9, s. 980-987
  • Tidskriftsartikel (refereegranskat)abstract
    • Intravenous thrombolysis for acute ischemic stroke in the Middle-East and North African (MENA) countries is still confined to the main urban and university hospitals. This was a prospective observational study to examine outcomes of intravenous thrombolysis-treated stroke patients in the MENA region compared to the non-MENA stroke cohort in the SITS International Registry. Results Of 32,160 patients with ischemic stroke registered using the SITS intravenous thrombolysis protocol between June 2014 and May 2016, 500 (1.6%) were recruited in MENA. Compared to non-MENA (all p < 0.001), median age in MENA was 55 versus 73 years, NIH Stroke Scale score 12 versus 9, onset-to-treatment time 138 versus 155 min and door-to-needle time 54 min versus 64 min. Hypertension was the most reported risk factor, but lower in MENA (51.7 vs. 69.7%). Diabetes was more frequent in MENA (28.5 vs. 20.8%) as well as smoking (20.8 vs. 15.9%). Hyperlipidemia was less observed in MENA (17.6 vs. 29.3%). Functional independence (mRS 0–2) at seven days or discharge was similar (53% vs. 52% in non-MENA), with mortality slightly lower in MENA (2.3% vs. 4.8%). SICH rates by SITS-MOST definition were low (<1.4%) in both groups. Conclusions Intravenous thrombolysis patients in MENA were younger, had more severe strokes and more often diabetes. Although stroke severity was higher in MENA, short-term functional independency and mortality were not worse compared to non-MENA, which could partly be explained by younger age and shorter OTT in MENA. Decreasing the burden of stroke in this young population should be prioritized.
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  • Al Rukn, S, et al. (författare)
  • Stroke in the Middle-East and North Africa: A 2-year prospective observational study of stroke characteristics in the region-Results from the Safe Implementation of Treatments in Stroke (SITS)-Middle-East and North African (MENA)
  • 2019
  • Ingår i: International journal of stroke : official journal of the International Stroke Society. - : SAGE Publications. - 1747-4949. ; 14:7, s. 715-722
  • Tidskriftsartikel (refereegranskat)abstract
    • Stroke incidence and mortality are reported to have increased in the Middle-East and North African (MENA) countries during the last decade. This was a prospective observational study to examine the baseline characteristics of stroke patients in the MENA region and to compare the MENA vs. the non-MENA stroke cohort in the Safe Implementation of Treatments in Stroke (SITS) International Registry. Results Of the 13,822 patients with ischemic and hemorrhagic stroke enrolled in the SITS-All Patients Protocol between June 2014 and May 2016, 5897 patients (43%) were recruited in MENA. The median onset-to-door time was 5 h (IQR: 2:20–13:00), National Institutes of Health Stroke Scale (NIHSS) score was 8 (4–13) and age was 65 years (56–76). Hypertension (66%) and diabetes (38%) were the prevailing risk factors; large artery stenosis > 50% (25.3%) and lacunar strokes (24.1%) were the most common ischemic stroke etiologies. In comparison, non-MENA countries displayed an onset-to-door time of 5:50 h (2:00–18:45), a median of NIHSS 6 (3–14), and a median age of 66 (56–76), with other large vessel disease and cardiac embolism as the main ischemic stroke etiologies. Hemorrhagic strokes (10%) were less common compared to non-MENA countries (13.9%). In MENA, only a low proportion of patients (21%) was admitted to stroke units. Conclusions MENA patients are slightly younger, have a higher prevalence of diabetes and slightly more severe ischemic strokes, commonly of atherosclerotic or microvascular etiology. Admission into stroke units and long-term follow-up need to be improved. It is suspected that cardiac embolism and atrial fibrillation are currently underdiagnosed in MENA countries.
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  • Billsten, Peter, et al. (författare)
  • Structural Changes of T4 Lysozyme upon Adsorption to Silica Nanoparticles Measured by Circular Dichroism
  • 1995
  • Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 1095-7103 .- 0021-9797. ; 175:1, s. 77-82
  • Tidskriftsartikel (refereegranskat)abstract
    • The change in the secondary structure of T4 lysozyme upon adsorption to silica particles was studied with circular dichroism. Two different mutants of the protein along with the wild type were investigated. The mutants differ from wild type by substitution of isoleucine for cysteine or tryptophan at position 3 and were chosen to represent a range of stability as quantified by their energies of thermal unfolding. The mutants differ in ΔG, at 65°C and pH 6.5, compared to the wild-type enzyme with -2.8 and 1.2 kcal/mol for the tryptophan and cysteine mutants, respectively. After adsorption to 9-nm silica nanoparticles for 90 min, a large change in the spectrum was observed for the less stable tryptophan mutant, while the changes were smaller for the wild type and the cysteine mutant. The spectral changes before and after adsorption corresponded to a calculated loss of α-helix of 12% for the wild type, 9% for the cysteine mutant, and 29% for the tryptophan mutant. Structural changes during adsorption of the proteins were also followed kinetically at 222 nm. The rate of conformational change differed among the three proteins and was fastest for the tryptophan mutant. In the case of the tryptophan mutant the time required for half of the measured change to occur was approximately 5 min, while for the cysteine mutant and the wild-type T4 lysozyme more than 10 min was required.
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  • Cellini, Andrea, 1991, et al. (författare)
  • Structural basis of the radical pair state in photolyases and cryptochromes
  • 2022
  • Ingår i: Chemical Communications. - : Royal Society of Chemistry (RSC). - 1359-7345 .- 1364-548X. ; , s. 4889-4892
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the structure of a photoactivated animal (6-4) photolyase in its radical pair state, captured by serial crystallography. We observe how a conserved asparigine moves towards the semiquinone FAD chromophore and stabilizes it by hydrogen bonding. Several amino acids around the final tryptophan radical rearrange, opening it up to the solvent. The structure explains how the protein environment stabilizes the radical pair state, which is crucial for function of (6-4) photolyases and cryptochromes.
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  • Claesson, Elin, 1989, et al. (författare)
  • The primary structural photoresponse of phytochrome proteins captured by a femtosecond X-ray laser
  • 2020
  • Ingår i: eLife. - 2050-084X. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Phytochrome proteins control the growth, reproduction, and photosynthesis of plants, fungi, and bacteria. Light is detected by a bilin cofactor, but it remains elusive how this leads to activation of the protein through structural changes. We present serial femtosecond X-ray crystallographic data of the chromophore-binding domains of a bacterial phytochrome at delay times of 1 ps and 10 ps after photoexcitation. The data reveal a twist of the D-ring, which leads to partial detachment of the chromophore from the protein. Unexpectedly, the conserved so-called pyrrole water is photodissociated from the chromophore, concomitant with movement of the A-ring and a key signaling aspartate. The changes are wired together by ultrafast backbone and water movements around the chromophore, channeling them into signal transduction towards the output domains. We suggest that the observed collective changes are important for the phytochrome photoresponse, explaining the earliest steps of how plants, fungi and bacteria sense red light.
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  • Daryapeyma, A, et al. (författare)
  • Perioperative cytokine response to infection associated with elective arterial surgery
  • 2014
  • Ingår i: Vascular and endovascular surgery. - : SAGE Publications. - 1938-9116 .- 1538-5744. ; 48:2, s. 116-122
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim was to assess the cytokine response to acute inflammation and infection in vascular surgery.Design of Study:Single-center, prospective cohort study.Methods:Blood samples from 96 consecutive patients undergoing elective vascular surgery were analyzed for C-reactive protein (CRP), total leukocyte counts (LPK), neutrophil CD64 expression, and cytokines using enzyme-linked immunosorbent assay.Results:Of the 25 investigated cytokines, 22 had lower postoperative mean values compared to preoperative values. Interleukin (IL) 6 (IL-6) was the only cytokine that increased significantly postoperatively. Combined analysis of CRP and CD64 together with IL-6 or IL-10 showed an individually unique association with postoperative infection ( P < .05).Conclusion:We have shown a positive correlation with perioperative infection for the proinflammatory cytokines and the anti-inflammatory cytokine IL-10 as well as a number of chemokines. To our knowledge, this is the first report linking IL-10 and chemokine plasma levels to perioperative infection in vascular surgery.
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  • Elfstrand, Lidia, et al. (författare)
  • Recrystallisation behaviour of native and processed waxy maize starch in relation to the molecular characteristics
  • 2004
  • Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617. ; 57:4, s. 389-400
  • Tidskriftsartikel (refereegranskat)abstract
    • Molecular characteristics were determined for native waxy maize starch and maize starch modified in different way (by mechanical treatment or/and acid hydrolysis). Recrystallisation behaviour was studied. Methods used in this study were MALLS, HPAEC-PAD, NMR, DSC, SEM, light microscopy. Five starch materials were subjected to storage under the same conditions in the presence of water (70 w/w%). Molecular weight, radius of gyration, initial crystallinity, and degree of polymerisation, degree of branching, chain length distribution profiles, were related to nucleation rate during the recrystallisation process, rate of recrystallisation, thermal stability and amount of obtained crystallinity. This allowed the following connections between the molecular characteristics and kinetic of recrystallisation to be proposed: Amylopectin molecular weight appeared to affect the number of starch crystallites formed and amount of crystallinity but not the stability of the rebuilt crystallites. The stability of rebuilt crystallites can be controlled by degree of polymerization, degree of branching and unit chain length distribution, characteristics which were similar for the starches. A mixture of two starches, with and without crystalline structure in initial state but with molecular weight in same range, were stored and scanned in order to understand possible cocrystallisation effects. (C) 2004 Elsevier Ltd. All rights reserved.
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  • Hacke, W, et al. (författare)
  • Effects of alteplase for acute stroke according to criteria defining the European Union and United States marketing authorizations: Individual-patient-data meta-analysis of randomized trials
  • 2018
  • Ingår i: International journal of stroke : official journal of the International Stroke Society. - : SAGE Publications. - 1747-4949. ; 13:2, s. 175-189
  • Tidskriftsartikel (refereegranskat)abstract
    • The recommended maximum age and time window for intravenous alteplase treatment of acute ischemic stroke differs between the Europe Union and United States. Aims We compared the effects of alteplase in cohorts defined by the current Europe Union or United States marketing approval labels, and by hypothetical revisions of the labels that would remove the Europe Union upper age limit or extend the United States treatment time window to 4.5 h. Methods We assessed outcomes in an individual-patient-data meta-analysis of eight randomized trials of intravenous alteplase (0.9 mg/kg) versus control for acute ischemic stroke. Outcomes included: excellent outcome (modified Rankin score 0–1) at 3–6 months, the distribution of modified Rankin score, symptomatic intracerebral hemorrhage, and 90-day mortality. Results Alteplase increased the odds of modified Rankin score 0–1 among 2449/6136 (40%) patients who met the current European Union label and 3491 (57%) patients who met the age-revised label (odds ratio 1.42, 95% CI 1.21−1.68 and 1.43, 1.23−1.65, respectively), but not in those outside the age-revised label (1.06, 0.90−1.26). By 90 days, there was no increased mortality in the current and age-revised cohorts (hazard ratios 0.98, 95% CI 0.76−1.25 and 1.01, 0.86–1.19, respectively) but mortality remained higher outside the age-revised label (1.19, 0.99–1.42). Similarly, alteplase increased the odds of modified Rankin score 0-1 among 1174/6136 (19%) patients who met the current US approval and 3326 (54%) who met a 4.5-h revised approval (odds ratio 1.55, 1.19−2.01 and 1.37, 1.17−1.59, respectively), but not for those outside the 4.5-h revised approval (1.14, 0.97−1.34). By 90 days, no increased mortality remained for the current and 4.5-h revised label cohorts (hazard ratios 0.99, 0.77−1.26 and 1.02, 0.87–1.20, respectively) but mortality remained higher outside the 4.5-h revised approval (1.17, 0.98–1.41). Conclusions An age-revised European Union label or 4.5-h-revised United States label would each increase the number of patients deriving net benefit from alteplase by 90 days after acute ischemic stroke, without excess mortality.
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39.
  • Harmenberg, U, et al. (författare)
  • Treatment and overall survival (OS) in metastatic renal cell carcinoma (mRCC): A Swedish population-based study (2000-2008).
  • 2012
  • Ingår i: JOURNAL OF CLINICAL ONCOLOGY. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 30:5
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • 389 Background: This retrospective register study assessed OS in all mRCC patients in Sweden diagnosed before (2000–2005) and after (2006–2008) the introduction of targeted therapies, plus factors and treatment options influencing OS. Methods: Three Swedish national health registers were used: the Swedish Cancer register (diagnosis and death), the National Patient Register (in-/out-patient data), and the Swedish Prescribed Drug Register. From 2000-2008, 3,243 patients were identified with mRCC; 602 were recorded as receiving 1st-line treatment. Cox proportional hazards regression analysis, including estimation of adjusted OS, was used in three models with the covariates: diagnosis period, age, gender, institution size, nephrectomy status, geographic region (all models); mRCC treatments, defined as any tyrosine kinase inhibitor (TKI; Model 1; n=417); sunitinib (SU), sorafenib (SO), and interferon-alfa (IFN-α) in the 1st-line setting (Model 2; n=602 [SU=244, SO=110, IFN-α=248]); and variations of these drugs as 1st- and 2nd-line treatment sequences (Model 3; n=602). Results: Amongst mRCC patients diagnosed from 2006–2008 compared with 2000–2005, median adjusted OS was 16.1 vs. 10.9 months, respectively (HR=0.76, 95% CI: 0.69, 0.83; P<0.001). In all three models, factors independently associated with significantly improved OS included female gender, large institution, and prior nephrectomy. Prescription of any TKI (Model 1: HR=0.82, 95% CI: 0.73, 0.93; P=0.002) and 1st-line SU treatment (Model 2: HR=0.79, 95% CI: 0.67, 0.94; P=0.007) were associated with significantly improved OS compared with other or no treatments. A similar significant improvement in OS was also confirmed for patients treated with SU only in Model 3; however, due to a low number of observations, the model had insufficient statistical power to be appropriate for all sequences. Conclusions: An improved OS for mRCC patients was demonstrated for the period 2006-2008 compared with 2000-2005. Although the observed survival advantage is multifactorial in origin, contribution of targeted therapies is highly probable. Of the drugs studied, given design limitations, only SU was associated with improved OS.
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40.
  • Hellstrom, G, et al. (författare)
  • Carotid artery blood flow and middle cerebral artery blood flow velocity during physical exercise
  • 1996
  • Ingår i: Journal of applied physiology (Bethesda, Md. : 1985). - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 81:1, s. 413-418
  • Tidskriftsartikel (refereegranskat)abstract
    • Factors controlling cerebral blood flow (CBF) during exercise are complex and incompletely known. Different techniques have shown partly contradictory results of changes in regional and global cerebral perfusion during dynamic exercise in healthy subjects. To elucidate the global CBF response to supine stepwise increasing physical exercise, we measured blood flow in the left common carotid artery (QCCA) and the left internal carotid artery (QICA) simultaneously with the blood flow velocity in the ipsilateral middle cerebral artery (VMCA) using duplex ultrasonography and transcranial Doppler ultrasonography. During moderate exercise intensity (60-67% of maximal capacity), the VMCA increased 14% (P < 0.001), the QICA 17% (P < 0.01), and the QCCA 33% (P < 0.001) compared with baseline values. High physical exercise intensity (80-90% of maximal capacity) tended to reduce VMCA and QICA compared with moderate exercise, in contrast to a continued increase in QCCA. The results indicate an increased global CBF during exercise. This increase was reduced during hard exercise due to a decrease of the arterial PCO2 secondary to hyperventilation.
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41.
  • Ismail, Hodan Ahmed, et al. (författare)
  • Subclass responses and their half-lives for antibodies against EBA175 and PfRh2 in naturally acquired immunity against Plasmodium falciparum malaria
  • 2014
  • Ingår i: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Plasmodium falciparum EBA175 and PfRh2 belong to two main families involved in parasite invasion, and both are potential vaccine candidates. Current knowledge is limited regarding which target antigens and subclasses of antibodies are actually important for protection, and how naturally acquired immunity is achieved. Methods: Repeated blood samples were collected from individuals in Nigeria over a period of almost one year. ELISA was used to analyse subclasses of IgG responses. Results: For both EBA175 (region III-V) and (a fragment of) PfRh2, the dominant antibody responses consisted of IgG1 and IgG3 followed by IgG2, while for PfRh2 there was also a relatively prominent response for IgG4. High levels of IgG1, IgG2 and IgG3 for EBA175 and total IgG for PfRh2 correlated significantly with a lower parasitaemia during the study period. Children with HbAS had higher levels of some subclasses compared to children with HbAA, while in adults the pattern was the opposite. The half-lives of IgG2 and IgG4 against EBA175 were clearly shorter than those for IgG1 and IgG3. Conclusion: EBA175 and PfRh2 are potential targets for protective antibodies since both correlated with lower parasitaemia. The shorter half-lives for IgG2 and IgG4 might explain why these subclasses are often considered less important in protection against malaria. Triggering the right subclass responses could be of critical importance in a successful vaccine. Further studies are needed to evaluate the role of haemoglobin polymorphisms and their malaria protective effects in this process.
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42.
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43.
  • Johansson, C., et al. (författare)
  • Atopy patch test reactions to Malassezia allergens differentiate subgroups of atopic dermatitis patients.
  • 2003
  • Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 1365-2133 .- 0007-0963. ; 148:3, s. 479-488
  • 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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  • Johansson, Sveneric, et al. (författare)
  • The FERRUM Project: New f-value Data for Fe II and Astrophysical Applications
  • 2002
  • Ingår i: Physica Scripta. - : Institute of Physics Publishing (IOPP). - 0281-1847 .- 0031-8949 .- 1402-4896. ; T100, s. 71-80
  • Konferensbidrag (refereegranskat)abstract
    • We present the FERRUM Project, an international collaboration aiming at a production and evaluation of oscillator strengths (transition probabilities) of selected spectral lines of singly ionized iron group elements, that are of astrophysical relevance. The results obtained include measurements and calculations of permitted and forbidden lines of Fe II. The data have been applied to both emission and absorption lines in astrophysical spectra. We make comparisons between experimental, theoretical and astrophysical f-values. We give a general review of the various measurements, and discuss the UV8 multiplet of Fe II around 1610 Šin detail.
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