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1.
  • Pulit, SL, et al. (författare)
  • Loci associated with ischaemic stroke and its subtypes (SiGN): a genome-wide association study.
  • 2016
  • Ingår i: The Lancet. Neurology. - 1474-4465. ; 15:2, s. 174-84
  • Tidskriftsartikel (refereegranskat)abstract
    • The discovery of disease-associated loci through genome-wide association studies (GWAS) is the leading genetic approach to the identification of novel biological pathways underlying diseases in humans. Until recently, GWAS in ischaemic stroke have been limited by small sample sizes and have yielded few loci associated with ischaemic stroke. We did a large-scale GWAS to identify additional susceptibility genes for stroke and its subtypes.To identify genetic loci associated with ischaemic stroke, we did a two-stage GWAS. In the first stage, we included 16851 cases with state-of-the-art phenotyping data and 32473 stroke-free controls. Cases were aged 16 to 104 years, recruited between 1989 and 2012, and subtypes of ischaemic stroke were recorded by centrally trained and certified investigators who used the web-based protocol, Causative Classification of Stroke (CCS). We constructed case-control strata by identifying samples that were genotyped on nearly identical arrays and were of similar genetic ancestral background. We cleaned and imputed data by use of dense imputation reference panels generated from whole-genome sequence data. We did genome-wide testing to identify stroke-associated loci within each stratum for each available phenotype, and we combined summary-level results using inverse variance-weighted fixed-effects meta-analysis. In the second stage, we did in-silico lookups of 1372 single nucleotide polymorphisms identified from the first stage GWAS in 20941 cases and 364736 unique stroke-free controls. The ischaemic stroke subtypes of these cases had previously been established with the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification system, in accordance with local standards. Results from the two stages were then jointly analysed in a final meta-analysis.We identified a novel locus (G allele at rs12122341) at 1p13.2 near TSPAN2 that was associated with large artery atherosclerosis-related stroke (first stage odds ratio [OR] 1·21, 95% CI 1·13-1·30, p=4·50×10(-8); joint OR 1·19, 1·12-1·26, p=1·30×10(-9)). Our results also supported robust associations with ischaemic stroke for four other loci that have been reported in previous studies, including PITX2 (first stage OR 1·39, 1·29-1·49, p=3·26×10(-19); joint OR 1·37, 1·30-1·45, p=2·79×10(-32)) and ZFHX3 (first stage OR 1·19, 1·11-1·27, p=2·93×10(-7); joint OR 1·17, 1·11-1·23, p=2·29×10(-10)) for cardioembolic stroke, and HDAC9 (first stage OR 1·29, 1·18-1·42, p=3·50×10(-8); joint OR 1·24, 1·15-1·33, p=4·52×10(-9)) for large artery atherosclerosis stroke. The 12q24 locus near ALDH2, which has previously been associated with all ischaemic stroke but not with any specific subtype, exceeded genome-wide significance in the meta-analysis of small artery stroke (first stage OR 1·20, 1·12-1·28, p=6·82×10(-8); joint OR 1·17, 1·11-1·23, p=2·92×10(-9)). Other loci associated with stroke in previous studies, including NINJ2, were not confirmed.Our results suggest that all ischaemic stroke-related loci previously implicated by GWAS are subtype specific. We identified a novel gene associated with large artery atherosclerosis stroke susceptibility. Follow-up studies will be necessary to establish whether the locus near TSPAN2 can be a target for a novel therapeutic approach to stroke prevention. In view of the subtype-specificity of the associations detected, the rich phenotyping data available in the Stroke Genetics Network (SiGN) are likely to be crucial for further genetic discoveries related to ischaemic stroke.US National Institute of Neurological Disorders and Stroke, National Institutes of Health.
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2.
  • Bratthall, G., et al. (författare)
  • Comparison of ready-to-use EMDOGAIN®-gel and EMDOGAIN® in patients with chronic adult periodontitis. A multicenter clinical study
  • 2001
  • Ingår i: Journal of Clinical Periodontology. - : John Wiley & Sons. - 0303-6979 .- 1600-051X. ; 28:10, s. 923-929
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The aim of this multicenter trial was to compare the clinical and radiographical outcome of a ready-to-use Emdogain®-gel (test) with the marketed Emdogain® (control). Methods: Subjects with bilateral infrabony defects ≥4 mm deep and ≥2 mm wide according to radiographs were selected. 88 subjects with probing pocket depth (PPD) ≥6 mm ≥1 month after supervised oral hygiene and scaling participated. At baseline plaque index, bleeding on probing, PPD and probing attachment level were recorded and reproducible radiographs for computer-based bone level measurements were taken. In each subject, 1 tooth was randomly treated with the test and 1 tooth with the control gel. Examinations were repeated 8 and 16 months post-operatively. Results: After 16 months, the mean test PPD was 4.1 mm and the mean control PPD 4.2 mm. The mean gain of attachment was 2.7 mm for test and 2.9 mm for the control sites, and the radiographic measurements demonstrated a mean gain of 1 mm for both test and control sites. Conclusion: This series of cases demonstrated a statistically significant reduction of pocket depths and gain of attachment and bone after 8 and 16 months with no difference between the 2 preparations.
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4.
  • Nylén, H., et al. (författare)
  • O KVV Auger emission versus resonant photoemission at the O K edge of high-Tc superconductors
  • 1998
  • Ingår i: Physica C: Superconductivity and its Applications. - 0921-4534. ; 300:3-4, s. 161-170
  • Tidskriftsartikel (refereegranskat)abstract
    • Photoelectron spectroscopy results on single crystals of the superconductors Bi2Sr2CaCu2O8,Bi2Sr 2CuO6, Ba0.6K0.4BiO3 and the semiconductor Ba0.9K0.1BiO3 are reported for the photon energy region around the O K absorption threshold. The development of the O-KVV Auger structure has been carefully monitored as a function of photon energy. A non-monotonic behavior displaying a feature at a constant binding energy of about 14 eV was found for Bi2Sr2CaCu2O8 and Bi2Sr2CuO6 in a narrow photon energy region of 1 eV at the main edge of the O K absorption spectrum around 530 eV. The corresponding enhancement, connected with the autoionization of O 2 p states, is absent in Ba1-xKxBiO3 in contrast to Bi2Sr2CaCu2O8 and Bi2Sr2CuO6. The resonant enhancement is more pronounced for Bi2Sr2CuO6 as compared to Bi2Sr2CaCu2O8, which can be explained by a lower charge carrier concentration in the former case, leading to a more localized nature of intermediate O 2 p states. The model parameters Cu d-d and O p-p Coulomb interactions and the charge transfer energy Δ are estimated from the experiments.
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6.
  • Bergemalm, Daniel, 1977-, et al. (författare)
  • Systemic Inflammation in Preclinical Ulcerative Colitis
  • 2021
  • Ingår i: Gastroenterology. - : AGA Institute. - 0016-5085 .- 1528-0012. ; 161:5, s. 1526-1539.e9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & Aims: Preclinical ulcerative colitis is poorly defined. We aimed to characterize the preclinical systemic inflammation in ulcerative colitis, using a comprehensive set of proteins.Methods: We obtained plasma samples biobanked from individuals who developed ulcerative colitis later in life (n = 72) and matched healthy controls (n = 140) within a population-based screening cohort. We measured 92 proteins related to inflammation using a proximity extension assay. The biologic relevance of these findings was validated in an inception cohort of patients with ulcerative colitis (n = 101) and healthy controls (n = 50). To examine the influence of genetic and environmental factors on these markers, a cohort of healthy twin siblings of patients with ulcerative colitis (n = 41) and matched healthy controls (n = 37) were explored.Results: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP-1) were up-regulated (P < .05) in preclinical ulcerative colitis compared with controls based on both univariate and multivariable models. Ingenuity Pathway Analyses identified several potential key regulators, including interleukin-1β, tumor necrosis factor, interferon-gamma, oncostatin M, nuclear factor-κB, interleukin-6, and interleukin-4. For validation, we built a multivariable model to predict disease in the inception cohort. The model discriminated treatment-naïve patients with ulcerative colitis from controls with leave-one-out cross-validation (area under the curve = 0.92). Consistently, MMP10, CXCL9, CXCL11, and MCP-1, but not CCL11 and SLAMF1, were significantly up-regulated among the healthy twin siblings, even though their relative abundances seemed higher in incident ulcerative colitis.Conclusions: A set of inflammatory proteins are up-regulated several years before a diagnosis of ulcerative colitis. These proteins were highly predictive of an ulcerative colitis diagnosis, and some seemed to be up-regulated already at exposure to genetic and environmental risk factors.
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7.
  • Bonkhoff, A. K., et al. (författare)
  • Sex-specific lesion pattern of functional outcomes after stroke
  • 2022
  • Ingår i: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 4:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Relying on neuroimaging and clinical data of 822 acute stroke patients, Bonkhoff et al. report substantially more detrimental effects of lesions in left-hemispheric posterior circulation regions on functional outcomes in women compared to men. These findings may motivate a sex-specific clinical stroke management to improve outcomes in the longer term. Stroke represents a considerable burden of disease for both men and women. However, a growing body of literature suggests clinically relevant sex differences in the underlying causes, presentations and outcomes of acute ischaemic stroke. In a recent study, we reported sex divergences in lesion topographies: specific to women, acute stroke severity was linked to lesions in the left-hemispheric posterior circulation. We here determined whether these sex-specific brain manifestations also affect long-term outcomes. We relied on 822 acute ischaemic patients [age: 64.7 (15.0) years, 39% women] originating from the multi-centre MRI-GENIE study to model unfavourable outcomes (modified Rankin Scale >2) based on acute neuroimaging data in a Bayesian hierarchical framework. Lesions encompassing bilateral subcortical nuclei and left-lateralized regions in proximity to the insula explained outcomes across men and women (area under the curve = 0.81). A pattern of left-hemispheric posterior circulation brain regions, combining left hippocampus, precuneus, fusiform and lingual gyrus, occipital pole and latero-occipital cortex, showed a substantially higher relevance in explaining functional outcomes in women compared to men [mean difference of Bayesian posterior distributions (men - women) = -0.295 (90% highest posterior density interval = -0.556 to -0.068)]. Once validated in prospective studies, our findings may motivate a sex-specific approach to clinical stroke management and hold the promise of enhancing outcomes on a population level.
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9.
  • Dorvall, Malin, 1991, et al. (författare)
  • Mosaic Loss of Chromosome Y Is Associated With Functional Outcome After Ischemic Stroke.
  • 2023
  • Ingår i: Stroke. - : Wolters Kluwer. - 1524-4628 .- 0039-2499. ; 54:9, s. 2434-2437
  • Tidskriftsartikel (refereegranskat)abstract
    • Mosaic loss of chromosome Y (LOY) is associated with cardiovascular and neurodegenerative diseases in men, and genetic predisposition to LOY is associated with poor poststroke outcome. We, therefore, tested the hypothesis that LOY itself is associated with functional outcome after ischemic stroke.The study comprised male patients with ischemic stroke from the cohort studies SAHLSIS2 (Sahlgrenska Academy Study on Ischemic Stroke Phase 2; n=588) and LSR (Lund Stroke Register; n=735). We used binary logistic regression to analyze associations between LOY, determined by DNA microarray intensity data, and poor 3-month functional outcome (modified Rankin Scale score, >2) in each cohort separately and combined. Patients who received recanalization therapy were excluded from sensitivity analyses.LOY was associated with about 2.5-fold increased risk of poor outcome in univariable analyses (P<0.001). This association withstood separate adjustment for stroke severity and diabetes in both cohorts but not age. In sensitivity analyses restricted to the nonrecanalization group (n=987 in the combined cohort), the association was significant also after separate adjustment for age (odds ratio, 1.6 [95% CI, 1.1-2.4]) and when additionally adjusting for stroke severity and diabetes (odds ratio, 1.6 [95% CI, 1.1-2.5]).We observed an association between LOY and poor outcome after ischemic stroke in patients not receiving recanalization therapy. Future studies on LOY and other somatic genetic alterations in larger stroke cohorts are warranted.
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10.
  • E., Svensson, et al. (författare)
  • Risk factors for spontaneous intracerebral hemorrhage
  • 2018
  • Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9881 .- 2396-9873. ; 3:1 Suppl, s. 60-61
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Background and Aims: Results from prior studies of risk factors for intracerebral hemorrhage (ICH) are inconsistent. Few studies have investigated risk factors measured before the event and separately for different locations of ICH. We investigated risk factors for incident ICH in the population-based Malmö Diet and Cancer cohort. Method: Baseline information, assessed by a questionnaire and in a physical examination, was gathered from 28,416 subjects without a history of ICH. ICH cases (n=333) were identified using local and national patient registers during follow-up (mean follow-up time 18.4 years), validated by review of hospital records, and classified as lobar or non-lobar. Potential risk factors were studied using Cox regression. Results: The following factors were significantly (p
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11.
  • Fejrskov, Anja, et al. (författare)
  • Novel biomarker profiles to improve individual diagnosis and prognosis in patients with suspected inflammatory bowel disease : protocol for the Nordic inception cohort study (NORDTREAT)
  • 2024
  • Ingår i: BMJ Open. - : BioMed Central (BMC). - 2044-6055. ; 14:5
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, can be challenging to diagnose, and treatment outcomes are difficult to predict. In the NORDTREAT cohort study, a Nordic prospective multicentre study, we aim to identify novel molecular biomarkers of diagnostic value by assessing the diagnostic test accuracy (cross-sectionally), as well as the prognostic utility when used as prognostic markers in the long-term (cohort study). In the diagnostic test accuracy study, the primary outcome is a successful diagnosis using one or more novel index tests at baseline compared with the ECCO criteria as the reference standard. The composite outcome of the prognostic utility study is 'severe IBD' within 52 weeks from inclusion, defined as one or more of the following three events: IBD-related surgery, IBD-related hospitalisation or IBD-related death.METHODS AND ANALYSIS: We aim to recruit 800 patients referred on suspicion of IBD to this longitudinal observational study, a collaboration between 11 inclusion sites in Denmark, Iceland, Norway and Sweden. Inclusion will occur from February 2022 until December 2023 with screening and baseline visits for all participants and three outcome visits at weeks 12, 26 and 52 after baseline for IBD-diagnosed patients. Biological material (blood, faeces, biopsies, urine and hair), clinical data and lifestyle information will be collected during these scheduled visits.ETHICS AND DISSEMINATION: This study will explore novel biomarkers to improve diagnostic accuracy and prediction of disease progression, thereby improving medical therapy and the quality of life for patients with IBD.The study is approved by the Ethics Committee (DK: S-20200051, v1.4, 16.10.2021; IS: VSNb2021070006/03.01, NO: 193064; SE: DNR 2021-05090) and the Danish Data Protecting Agency (20/54594). Results will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences.CLINICAL TRIAL REGISTRATION NUMBER: NCT05414578; Pre-results.
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12.
  • Geraldi, Joana G, et al. (författare)
  • Innovation in project management: Voices of researchers
  • 2008
  • Ingår i: International Journal of Project Management. - : Elsevier BV. - 0263-7863 .- 1873-4634. ; 26:5, s. 586-589
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper reports and reflects on the discussions about the nature of the discipline of project management that took place during the 8th conference of the International Research Network of Organizing by Projects (IRNOP VIII), held in Brighton in September 2007. The discussions started with the provocative motion “This house believes that we no longer need the discipline of project management”. The arguments are organised in the following areas: the use of the traditional body of knowledge by practitioners and by academics; the use of project management as a knowledge field by practitioners and by academics. The discussions indicate that project management research is in a fruitful moment of revolution of paradigms. We wish that the new paradigm accepts the plurality of research in projects and we need discussions supporting and also refusing the ‘motion’, and by this means, proposing answers, rather than the answer, to the future of ‘the project management discipline’.
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13.
  • Hermansson, Cecilia, et al. (författare)
  • DN Debatt: Klimatlagen kräver att regeringen ändrar politik
  • 2022
  • Ingår i: Dagens nyheter (DN debatt). - 1101-2447.
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • Nästa år ska regeringen enligt klimatlagen presentera en handlingsplan för hur Sverige ska nå klimatmålen. Minst ett dussin myndigheter har bidragit med underlag. Men inte ens om samtliga förslag i dessa rapporter genomförs kommer det att räcka för att fylla det gap som har uppstått med den nya regeringens politik, skriver Klimatpolitiska rådet.
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14.
  • Hermansson, Cecilia, et al. (författare)
  • Klimatpolitiska rådets rapport 2023
  • 2023
  • Rapport (populärvet., debatt m.m.)abstract
    • Stigande halter av växthusgaser i atmosfären har rubbat balansen i jordens klimatsystem vilket har medfört en snabbt stigande global medeltemperatur. Den globala uppvärmningen ligger nu på drygt 1,1 grader jämfört med förindustriell tid. Utöver högre temperaturer har detta lett till fler extrema väderhändelser, smältande isar och stigande havsnivåer. De ekologiska, ekonomiska och sociala effekterna av klimatförändringarna blir allt påtagligare.
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15.
  • Kalla, R., et al. (författare)
  • Serum proteomic profiling at diagnosis predicts clinical course, and need for intensification of treatment in inflammatory bowel disease
  • 2021
  • Ingår i: Journal of Crohn's & Colitis. - : Elsevier. - 1873-9946 .- 1876-4479. ; 15:5, s. 699-708
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Success in personalised medicine in complex disease is critically dependent on biomarker discovery. We profiled serum proteins using a novel proximity extension assay (PEA) to identify diagnostic and prognostic biomarkers in inflammatory bowel disease (IBD).METHODS: We conducted a prospective case-control study in an inception cohort of 552 patients (328 IBD, 224 non-IBD), profiling proteins recruited across 6 centres. Treatment escalation was characterised by the need for biological agents or surgery after initial disease remission. Nested leave-one-out cross validation was used to examine the performance of diagnostic and prognostic proteins.RESULTS: A total of 66 serum proteins differentiated IBD from symptomatic non-IBD controls including MMP-12 (Holm adjusted p=4.1×10 -23 ) and OSM (p=3.7×10 -16). Nine of these proteins associate with cis- germline variation (59 independent SNPs). Fifteen proteins, all members of TNF independent pathways including IL-1 and OSM predicted escalation, over a median follow-up of 518 (IQR 224-756) days. Nested cross-validation of the entire data set allows characterisation of 5-protein-models (96% comprising five core proteins ITGAV, EpCAM, IL18, SLAMF7, and IL8) which define a high-risk subgroup in IBD (HR 3.90, CI: 2.43-6.26), or allows distinct 2, and 3 protein models for UC and CD respectively.CONCLUSION: We have characterised a simple oligo-protein panel that has the potential to identify IBD from symptomatic controls and to predict future disease course. Further prospective work is required to validate our findings.
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16.
  • Kalla, R., et al. (författare)
  • Whole blood profiling of T-cell derived miRNA allows the development of prognostic models in inflammatory bowel disease
  • 2020
  • Ingår i: Journal of Crohn's & Colitis. - : Elsevier. - 1873-9946 .- 1876-4479. ; 14:12, s. 1724-1733
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: MicroRNAs (miRNAs) are cell-specific small non-coding RNAs that can regulate gene expression and have been implicated in Inflammatory Bowel Disease (IBD) pathogenesis. In our study, we define the cell-specific miRNA profiles and investigate its biomarker potential in IBD.METHODS: In a 2-stage prospective multi-centre case control study, Next Generation sequencing was performed on a discovery cohort of immunomagnetically separated leucocytes from 32 patients (9 CD, 14 UC, 8 healthy controls) and differentially expressed signals were validated in whole blood in 294 patients (97 UC, 98 CD, 98 non-IBD) using quantitative PCR. Correlations were analysed with phenotype, including need for early treatment escalation as a marker of progressive disease using Cox proportional hazards.RESULTS: In stage 1, each leucocyte subset (CD4+ and CD8+ T-cells and CD14+ monocytes) was analysed in IBD and controls. Three specific miRNAs differentiated IBD from controls in CD4+ T-cells, including miR-1307-3p (p=0.01), miR-3615 (p=0.02) and miR-4792 (p=0.01). In the extension cohort, in stage 2, miR-1307-3p was able to predict disease progression in IBD (HR 1.98, IQR:1.20-3.27;logrank p=1.80×10-3), in particular CD (HR 2.81; IQR: 1.11-3.53, p=6.50×10-4). Using blood-based multimarker miRNA models, the estimated chance of escalation in CD was 83% if 2 or more criteria were met and 90% for UC if 3 or more criteria are met.INTERPRETATION: We have identified and validated unique CD4+ T-cell miRNAs that are differentially regulated in IBD. These miRNAs may be able to predict treatment escalation and have the potential for clinical translation; further prospective evaluation is now indicated.
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17.
  • Klimov, A. B., et al. (författare)
  • Assessing the Polarization of a Quantum Field from Stokes Fluctuations
  • 2010
  • Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 105:15, s. 153602-
  • Tidskriftsartikel (refereegranskat)abstract
    • We propose an operational degree of polarization in terms of the variance of the Stokes vector minimized over all the directions of the Poincare sphere. We examine the properties of this second-order definition and carry out its experimental determination. Quantum states with the same standard (first-order) degree of polarization are correctly discriminated by this new measure. We argue that a comprehensive quantum characterization of polarization properties requires a whole hierarchy of higher-order degrees.
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18.
  • Lutgendorff, Femke, 1981-, et al. (författare)
  • Probiotics enhance pancreatic glutathione biosynthesis and reduce oxidative stress in experimental acute pancreatitis
  • 2008
  • Ingår i: American Journal of Physiology - Gastrointestinal and Liver Physiology. - : American Physiological Society. - 0193-1857 .- 1522-1547. ; 295:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Factors determining severity of acute pancreatitis (AP) are poorly understood. Oxidative stress causes acinar cell injury and contributes to the severity, whereas prophylactic probiotics ameliorate experimental pancreatitis. Our objective was to study how probiotics affect oxidative stress, inflammation, and acinar cell injury during the early phase of AP. Fifty-three male Sprague-Dawley rats were randomly allocated into groups: 1) control, 2) sham procedure, 3) AP with no treatment, 4) AP with probiotics, and 5) AP with placebo. AP was induced under general anesthesia by intraductal glycodeoxycholate infusion (15 mM) and intravenous cerulein (5 μg·kg-1·h-1, for 6 h). Daily probiotics or placebo were administered intragastrically, starting 5 days prior to AP. After cerulein infusion, pancreas samples were collected for analysis including lipid peroxidation, glutathione, glutamate-cysteine-ligase activity, histological grading of pancreatic injury, and NF-κB activation. The severity of pancreatic injury correlated to oxidative damage (r = 0.9) and was ameliorated by probiotics (1.5 vs. placebo 5.5, P = 0.014). AP-induced NF-κB activation was reduced by probiotics (0.20 vs. placebo 0.53 OD 450nm/mg nuclear protein, P < 0.001). Probiotics attenuated AP-induced lipid peroxidation (0.25 vs. placebo 0.51 pmol malondialdehyde/mg protein, P < 0.001). Not only was AP-induced glutathione depletion prevented (8.81 vs. placebo 4.1 μmol/mg protein, P < 0.001), probiotic pretreatment even increased glutathione compared with sham rats (8.81 vs. sham 6.18 μmol/mg protein, P < 0.001). Biosynthesis of glutathione (glutamate-cysteine-ligase activity) was enhanced in probiotic-pretreated animals. Probiotics enhanced the biosynthesis of glutathione, which may have reduced activation of inflammation and acinar cell injury and ameliorated experimental AP, via a reduction in oxidative stress. Copyright © 2008 the American Physiological Society.
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19.
  • Lutgendorff, Femke, et al. (författare)
  • Probiotics prevent intestinal barrier dysfunction in acute pancreatitis in rats via induction of ileal mucosal glutathione biosynthesis.
  • 2009
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:2, s. e4512-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: During acute pancreatitis (AP), oxidative stress contributes to intestinal barrier failure. We studied actions of multispecies probiotics on barrier dysfunction and oxidative stress in experimental AP. METHODOLOGY/PRINCIPAL FINDINGS: Fifty-three male Spraque-Dawley rats were randomly allocated into five groups: 1) controls, non-operated, 2) sham-operated, 3) AP, 4) AP and probiotics and 5) AP and placebo. AP was induced by intraductal glycodeoxycholate infusion and intravenous cerulein (6 h). Daily probiotics or placebo were administered intragastrically, starting five days prior to AP. After cerulein infusion, ileal mucosa was collected for measurements of E. coli K12 and (51)Cr-EDTA passage in Ussing chambers. Tight junction proteins were investigated by confocal immunofluorescence imaging. Ileal mucosal apoptosis, lipid peroxidation, and glutathione levels were determined and glutamate-cysteine-ligase activity and expression were quantified. AP-induced barrier dysfunction was characterized by epithelial cell apoptosis and alterations of tight junction proteins (i.e. disruption of occludin and claudin-1 and up-regulation of claudin-2) and correlated with lipid peroxidation (r>0.8). Probiotic pre-treatment diminished the AP-induced increase in E. coli passage (probiotics 57.4+/-33.5 vs. placebo 223.7+/-93.7 a.u.; P<0.001), (51)Cr-EDTA flux (16.7+/-10.1 vs. 32.1+/-10.0 cm/s10(-6); P<0.005), apoptosis, lipid peroxidation (0.42+/-0.13 vs. 1.62+/-0.53 pmol MDA/mg protein; P<0.001), and prevented tight junction protein disruption. AP-induced decline in glutathione was not only prevented (14.33+/-1.47 vs. 8.82+/-1.30 nmol/mg protein, P<0.001), but probiotics even increased mucosal glutathione compared with sham rats (14.33+/-1.47 vs. 10.70+/-1.74 nmol/mg protein, P<0.001). Glutamate-cysteine-ligase activity, which is rate-limiting in glutathione biosynthesis, was enhanced in probiotic pre-treated animals (probiotics 2.88+/-1.21 vs. placebo 1.94+/-0.55 nmol/min/mg protein; P<0.05) coinciding with an increase in mRNA expression of glutamate-cysteine-ligase catalytic (GCLc) and modifier (GCLm) subunits. CONCLUSIONS: Probiotic pre-treatment diminished AP-induced intestinal barrier dysfunction and prevented oxidative stress via mechanisms mainly involving mucosal glutathione biosynthesis.
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21.
  • Mayfield, L., et al. (författare)
  • Root conditioning using EDTA gel as an adjunct to surgical therapy for the treatment of intraosseous periodontal defects
  • 1998
  • Ingår i: Journal of Clinical Periodontology. - : John Wiley & Sons. - 0303-6979 .- 1600-051X. ; 25:9, s. 707-714
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this clinical study was to compare the treatment outcome following root surface conditioning using an EDTA gel preparation in conjunction with surgical therapy with that following conventional flap surgery in periodontal intraosseous defects. 36 patients, each of them contributing one intraosseous defect ≥4 mm in depth participated. Defect sites had a probing pocket depth ≥5 mm and bled on probing following hygienic treatment phase. No furcation involvement or endodontic complications were present. In the EDTA group, 18 consecutive patients, defects were treated by root conditioning with EDTA gel for 3 minutes in combination with surgical therapy. In the control group, 18 patients, conventional flap surgery was performed without root conditioning. Chlorhexidine rinsings 0.2% were prescribed following surgery for 2-3 weeks with modified oral hygiene instruction. A strict recall program was implemented including professional prophylaxis and oral hygiene reinforcement every 4-6 weeks until 6-month re-evaluation. Baseline probing pocket depths and defect depths of 7.1±1.3 mm and 6.9±1.6 mm in the EDTA group and 7.6±1.9 mm and 6.6±1.7 mm, respectively, in the control group were measured. 6-month clinical results showed a significant probing attachment level gain of 1.8±1.5 mm and 1.0±1.7 mm in the EDTA and control groups respectively. A probing bone gain of 1.0±1.3 mm in the EDTA group was measured with a non-significant gain of 0.4±1.2 mm in the control group. Radiographic analysis confirmed these results. There were no statistically significant differences in treatment outcome between the group treated by root conditioning in combination with flap surgery and conventional flap surgery alone. 
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22.
  • Qvarford, M., et al. (författare)
  • X-ray absorption study of oxygen in the high-Tc superconductor Bi2Sr2CaCu2O8 near the interfaces to Cu, Ag and Au
  • 1996
  • Ingår i: Physica C: Superconductivity and its Applications. - : Elsevier BV. - 0921-4534 .- 1873-2143. ; 265:1-2, s. 113-120
  • Tidskriftsartikel (refereegranskat)abstract
    • The influence on O 2p holes in single crystalline Bi2Sr2CaCu2O8 upon the interface formation to Cu, Ag and Au has been studied by O K edge X-ray absorption measurements. It was found that Cu reduces the amount of doping induced O 2p holes significantly in the vicinity of the interface, whereas Ag and Au gave a much smaller reduction of these states. Photoemission spectra confirmed previous findings that Cu causes a strong chemical reaction at the Bi-O surface of Bi2Sr2CaCu2O8, in contrast to Ag and Au which induced only a minimal reaction. The results support the opinion that the Bi-O layers are essential for the doping of the Cu-O2 layers in Bi2Sr2CaCu2O8.
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23.
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24.
  • Sánchez-Soto, L. L., et al. (författare)
  • Polarization correlations in quantum optics
  • 2011
  • Ingår i: Opt.InfoBase Conf. Papers. - 9781557529282
  • Konferensbidrag (refereegranskat)abstract
    • The standard degree of polarization involves exclusively first-order moments of the Stokes variables. This may be sufficient for most classical problems, but for quantum fields higher-order correlations are crucial. We claim that a complete polarization characterization must involve a whole hierarchy of polarization degrees constructed order by order, as it happens in coherence theory. We present here a second-order degree and determine it experimentally.
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25.
  • Sonnenwald, D.H., et al. (författare)
  • Illuminating collaboration in emergency health care situations : paramedic-physician collaboration and 3D telepresence technology
  • 2014
  • Ingår i: Information research. - : University of Sheffield: Department of Information Studies. - 1368-1613. ; 19:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction. This paper focuses on paramedics' perspectives regarding paramedic-physician collaboration today, and their perspectives regarding the potential of 3D telepresence technology in the future. Method. Interviews were conducted with forty practicing paramedics. Analysis. The interview data were analysed using open and axial coding. An agreement of 0.82 using Cohen's kappa inter-coder reliability measure was reached. After coding was completed themes and relationships among codes were synthesised using topic memos. Results. Paramedics expressed concern about the lack of respect and trust exhibited towards them by other medical professionals. They discussed how they paint the picture for physicians and the importance of the physician trusting the paramedic. They further reported 3D telepresence technology would make their work visible in ways not previously possible. They also reported the technology would require additional training, changes to existing financial models used in emergency health care, and increased access to physicians. Conclusions. Teaching collaboration skills and strategies to physicians and paramedics could benefit their collaboration today, and increase their readiness to effectively use collaboration technologies in the future.
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26.
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27.
  • Söderholm, Jonas, 1978, et al. (författare)
  • Impact of Soluble CD26 on Treatment Outcome and Hepatitis C Virus-Specific T Cells in Chronic Hepatitis C Virus Genotype 1 Infection
  • 2013
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Interferon and ribavirin therapy for chronic hepatitis C virus (HCV) infection yields sustained virological response (SVR) rates of 50–80%. Several factors such as non-1 genotype, beneficial IL28B genetic variants, low baseline IP-10, and the functionality of HCV-specific T cells predict SVR. With the pending introduction of new therapies for HCV entailing very rapid clearance of plasma HCV RNA, the importance of baseline biomarkers likely will increase in order to tailor therapy. CD26 (DPPIV) truncates the chemokine IP-10 into a shorter antagonistic form, and this truncation of IP-10 has been suggested to influence treatment outcome in patients with chronic HCV infection patients. In addition, previous reports have shown CD26 to be a co-stimulator for T cells. The aim of the present study was to assess the utility of CD26 as a biomarker for treatment outcome in chronic hepatitis C and to define its association with HCV-specific T cells. Methods Baseline plasma from 153 genotype 1 and 58 genotype 2/3 infected patients enrolled in an international multicenter phase III trial (DITTO-HCV) and 36 genotype 1 infected patients participating in a Swedish trial (TTG1) were evaluated regarding baseline soluble CD26 (sCD26) and the functionality of HCV-specific CD8+ T cells. Results Genotype 1 infected patients achieving SVR in the DITTO (P = 0.002) and the TTG1 (P = 0.02) studies had lower pretreatment sCD26 concentrations compared with non-SVR patients. Sixty-five percent of patients with sCD26 concentrations below 600 ng/mL achieved SVR compared with 39% of the patients with sCD26 exceeding 600 ng/mL (P = 0.01). Patients with sCD26 concentrations below 600 ng/mL had significantly higher frequencies of HCV-specific CD8+ T cells (P = 0.02). Conclusions Low baseline systemic concentrations of sCD26 predict favorable treatment outcome in chronic HCV infection and may be associated with higher blood counts of HCV-specific CD8+ T cells.
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28.
  • Söderholm, J., et al. (författare)
  • Quantum polarization characterization and tomography
  • 2012
  • Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 14, s. 115014-
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a complete polarization characterization of any quantum state of two orthogonal polarization modes and give a systematic measurement procedure to collect the necessary data. Full characterization requires measurements of the photon number in both modes and linear optics. In the case where only the photon-number difference can be determined, a limited but useful characterization is obtained. The characteristic Stokes moment profiles are given for several common quantum states.
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29.
  • Söderholm, M, et al. (författare)
  • Exome array analysis of ischaemic stroke : results from a southern Swedish study
  • 2016
  • Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 23:12, s. 1722-1728
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND PURPOSE: Genome-wide association (GWA) studies have identified a few risk loci for ischaemic stroke, but these variants explain only a small part of the genetic contribution to the disease. Coding variants associated with amino acid substitutions or premature termination of protein synthesis could have a large effect on disease risk. We performed an exome array analysis for ischaemic stroke.METHODS: Patients with ischaemic stroke (n = 2385) and control subjects (n = 6077) from three Swedish studies were genotyped with the Illumina HumanOmniExpressExome BeadChip. Single-variant association analysis and gene-based tests were performed of exome variants with minor allele frequency of < 5%. A separate GWA analysis was also performed, based on 700 000 genotyped common markers and subsequent imputation.RESULTS: No exome variant or gene was significantly associated with all ischaemic stroke after Bonferroni correction (all P > 1.8 × 10(-6) for single-variant and >4.15 × 10(-6) for gene-based analysis). The strongest association in single-variant analysis was found for a missense variant in the DNAH11 gene (rs143362381; P = 5.01 × 10(-6) ). In gene-based tests, the strongest association was for the ZBTB20 gene (P = 7.9 × 10(-5) ). The GWA analysis showed that the sample was homogenous (median genomic inflation factor = 1.006). No genome-wide significant association with overall ischaemic stroke risk was found. However, previously reported associations for the PITX2 and ZFHX3 gene loci with cardioembolic stroke subtype were replicated (P = 7 × 10(-15) and 6 × 10(-3) ).CONCLUSIONS: This exome array analysis did not identify any single variants or genes reaching the pre-defined significance level for association with ischaemic stroke. Further studies on exome variants should be performed in even larger, well-defined and subtyped samples.
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