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| 3. |
- Kuhle, J, et al.
(författare)
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A 10-year follow-up of the European multicenter trial of interferon β-1b in secondary-progressive multiple sclerosis
- 2016
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 22:4, s. 533-543
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Tidskriftsartikel (refereegranskat)abstract
- To explore long-term effects of treatment and prognostic relevance of variables assessed at baseline and during the European secondary progressive multiple sclerosis (SPMS) trial of interferon beta 1b (IFNB-1b). Methods: We assessed 362 patients (60% female; median age 41 years; Expanded Disability Status Scale (EDSS): 5.5; 51% randomized to IFNB-1b) for their EDSS and treatment history after 10 years. Non-parametric analysis of covariance (ANCOVA) and multivariate linear regression models were applied. Results: Median EDSS was 6.0 at the end of the randomized controlled trial (RCT), in the IFNB-1b and placebo groups, and 7.0 in long-term follow-up patients (those receiving IFNB-1b in the RCT were 6.5 and those receiving placebo in the RCT were 7.0; p = 0.086). 24 patients (6.6%) were deceased. The EDSS at baseline and the EDSS change during the RCT were the most important predictors of the EDSS 10 years later (partial R2: 0.47). The ability to predict changes in EDSS 10 years after the RCT was limited ( R2: 0.12). Magnetic resonance imaging (MRI) measures remained in the predictive models, but explained < 5% of the variability. Conclusions: The results from this analysis did not provide convincing evidence to support a favorable long-term outcome in those patients allocated IFNB-1b during the RCT, in our SPMS cohort. The progressive stage of the disease remains largely unpredictable by clinical and conventional MRI measures, so better prognostic markers are needed.
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| 4. |
- Hilbert, Kevin, et al.
(författare)
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Cortical and Subcortical Brain Alterations in Specific Phobia and Its Animal and Blood-Injection-Injury Subtypes: A Mega-Analysis From the ENIGMA Anxiety Working Group.
- 2024
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Ingår i: The American Journal of Psychiatry. - 1535-7228. ; 181:8, s. 728-740
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Tidskriftsartikel (refereegranskat)abstract
- Specific phobia is a common anxiety disorder, but the literature on associated brain structure alterations exhibits substantial gaps. The ENIGMA Anxiety Working Group examined brain structure differences between individuals with specific phobias and healthy control subjects as well as between the animal and blood-injection-injury (BII) subtypes of specific phobia. Additionally, the authors investigated associations of brain structure with symptom severity and age (youths vs. adults).Data sets from 31 original studies were combined to create a final sample with 1,452 participants with phobia and 2,991 healthy participants (62.7% female; ages 5-90). Imaging processing and quality control were performed using established ENIGMA protocols. Subcortical volumes as well as cortical surface area and thickness were examined in a preregistered analysis.Compared with the healthy control group, the phobia group showed mostly smaller subcortical volumes, mixed surface differences, and larger cortical thickness across a substantial number of regions. The phobia subgroups also showed differences, including, as hypothesized, larger medial orbitofrontal cortex thickness in BII phobia (N=182) compared with animal phobia (N=739). All findings were driven by adult participants; no significant results were observed in children and adolescents.Brain alterations associated with specific phobia exceeded those of other anxiety disorders in comparable analyses in extent and effect size and were not limited to reductions in brain structure. Moreover, phenomenological differences between phobia subgroups were reflected in diverging neural underpinnings, including brain areas related to fear processing and higher cognitive processes. The findings implicate brain structure alterations in specific phobia, although subcortical alterations in particular may also relate to broader internalizing psychopathology.
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| 7. |
- Gilbert, M. Thomas P., et al.
(författare)
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Intraspecific phylogenetic analysis of Siberian woolly mammoths using complete mitochondrial genomes
- 2008
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 105:24, s. 8327-8332
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Tidskriftsartikel (refereegranskat)abstract
- We report five new complete mitochondrial DNA (mtDNA) genomes of Siberian woolly mammoth (Mammuthus primigenius), sequenced with up to 73-fold coverage from DNA extracted from hair shaft material. Three of the sequences present the first complete mtDNA genomes of mammoth clade II. Analysis of these and 13 recently published mtDNA genomes demonstrates the existence of two apparently sympatric mtDNA clades that exhibit high interclade divergence. The analytical power afforded by the analysis of the complete mtDNA genomes reveals a surprisingly ancient coalescence age of the two clades, approximate to 1-2 million years, depending on the calibration technique. Furthermore, statistical analysis of the temporal distribution of the C-14 ages of these and previously identified members of the two mammoth clades suggests that clade II went extinct before clade I. Modeling of protein structures failed to indicate any important functional difference between genomes belonging to the two clades, suggesting that the loss of clade II more likely is due to genetic drift than a selective sweep.
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| 10. |
- Meeuwsen, John A.L., et al.
(författare)
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High levels of (un)switched memory B cells are associated with better outcome in patients with advanced atherosclerotic disease
- 2017
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 6:9
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Tidskriftsartikel (refereegranskat)abstract
- Background--Atherosclerosis is an inflammatory lipid disorder and the main underlying pathology of acute ischemic events. Despite a vast amount of data from murine atherosclerosis models, evidence of B-cell involvement in human atherosclerotic disease is limited. We therefore investigated the association of circulating B-cell subtypes with the occurrence of secondary cardiovascular events in advanced atherosclerotic disease. Methods and Results--This cohort study consists of 168 patients who were included in the Athero-Express biobank between 2009 and 2011. Before surgery, peripheral blood mononuclear cells were isolated and stored in liquid nitrogen. After gentle thawing of the peripheral blood mononuclear cells, different B-cell subtypes including naïve, (un)switched memory, and CD27+CD43+ B1-like B cells, were analyzed by flow cytometry. Univariable and multivariable Cox proportional hazard models were used to analyze associations between B-cell subtypes, circulating antibodies and secondary cardiovascular manifestations during the 3-year follow-up period. Mean age was 70.1±9.6 years, males represented 62.8% of the population, and 54 patients had secondary manifestations during follow-up. High numbers of unswitched memory cells were protective against secondary outcome (hazard ratio, 0.30 [95% CI, 0.13-0.69]; P < 0.01). Similar results were obtained for the switched memory cells that also showed to be protective against secondary outcome (hazard ratio, 0.33 [95% CI, 0.14-0.77]; P = 0.01). Conclusions--A high number of (un)switched memory B cells is associated with better outcome following carotid artery endarterectomy. These findings suggest a potential role for B-cell subsets in prediction and prevention of secondary cardiovascular events in patients with atherosclerosis.
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| 14. |
- Andersson, G, et al.
(författare)
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Regional cerebral blood flow during tinnitus : a PET case study with lidocaine and auditory stimulation.
- 2000
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Ingår i: Acta Otolaryngol. - 0001-6489. ; 120:8, s. 967-72
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Tidskriftsartikel (refereegranskat)abstract
- Brain imaging of tinnitus has suggested central correlates of tinnitus perception. This study presents positron emission tomographic (PET) measurements of regional cerebral blood flow (rCBF) in a female tinnitus patient with bilateral left dominant tinnitus. Lidocaine infusion (75 mg during 5 min (0.2 mg/kg/min)) resulted in a 75% reduction of tinnitus and a temporary abolition of the dominant tinnitus in her left ear. Regional CBF was measured in four conditions: i) at rest while concentrating on tinnitus, ii) following maximum effect of lidocaine, iii) during sound stimulation, and iv) the following day at rest while concentrating on tinnitus. Subtraction analyses showed that tinnitus was associated with increased rCBF in the left parieto-temporal auditory cortex, including the primary and secondary auditory cortex with a focus in the parietal cortex (Brodmann areas 39, 41, 42, 21, 22). Activations were also found in right frontal paralimbic areas (Brodmann areas 47, 49 and 15). Sound stimulation resulted in bilateral activation of auditory areas. It is suggested that tinnitus is processed in primary, secondary and integrative auditory cortical areas. Tinnitus perception may involve areas related to auditory attention, while emotional processing relates to temporofrontal paralimbic areas.
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| 18. |
- Björkbacka, H, et al.
(författare)
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Plasma stem cell factor levels are associated with risk of cardiovascular disease and death
- 2017
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 282:6, s. 508-521
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Stem cell factor (SCF) is a key growth factor for several types of stem and progenitor cells. There is experimental evidence that such cells are of importance for maintaining the integrity of the cardiovascular system. We investigated the association between circulating levels of SCF and risk for development of cardiovascular events and death.METHODS: SCF was analysed by the proximity extension assay technique in plasma from 4742 subjects participating in the Malmö Diet and Cancer Study. Cardiovascular events and death were monitored through national registers with a mean follow-up time of 19.2 years.RESULTS: Subjects with high baseline levels of SCF had lower cardiovascular (n = 340) and all-cause mortality (n = 1159) as well as a lower risk of heart failure (n = 177), stroke (n = 318) and myocardial infarction (n = 452). Smoking, diabetes and high alcohol consumption were associated with lower levels of SCF. Single nucleotide polymorphisms in the gene region encoding PDX1 C-terminal inhibiting factor 1 (PCIF1) and matrix metalloproteinase-9 were associated with plasma SCF levels. The highest SCF quartile remained independently associated with a lower risk of a lower risk of cardiovascular [hazard ratio and 95% confidence interval 0.59 (0.43-0.81)] and all-cause mortality [0.68 (0.57-0.81)], heart failure [0.50 (0.31-0.80)] and stroke [0.66 (0.47-0.92)], but not with MI [0.96 (0.72-1.27)] as compared with the lowest quartile when adjusting for traditional cardiovascular risk factors in Cox proportional hazard regression models.CONCLUSIONS: This prospective population-based study demonstrates that subjects with high levels of SCF have a lower risk of cardiovascular events and death. The findings provide clinical support for a protective role of SCF in maintaining cardiovascular integrity.
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| 19. |
- Cheng, Q., et al.
(författare)
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Clinical epidemiology of Guillain-Barré syndrome in adults in Sweden 1996-97 : A prospective study
- 2000
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 7:6, s. 685-692
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Tidskriftsartikel (refereegranskat)abstract
- We described clinical manifestations, outcomes, prognostic indicators and clinico-epidemiological subgroups for 53 adult patients with Guillain-Barré syndrome (GBS) in Sweden during the period 1996-97. These patients were identified from a population of 2.8 million inhabitants and prospectively followed up for one year by a network of neurologists. An additional 10 cases, of whom five were adults who had not been prospectively followed up, were not included in the analyses. At 6 months after onset 80% of the patients could walk without aid, while at 1 year 46% were fully recovered, 42% had mild residual signs or symptoms, 4% had moderate and 6% severe disabilities, and 2% had died. Intravenous human immunoglobulin or plasmapheresis were used in 72% of the patients. The sum of the Medical Research Council (MRC) score at nadir was found as the only significant predictor for residual signs at 1 year in a multivariate model. Three subgroups, with different clinico-epidemiological characteristics, were identified by using cluster analysis. In conclusion, GBS in Sweden is frequently preceded by a respiratory infection, is often treated with immunomodulatory therapies, and exhibits a high recovery rate and a low fatality rate.
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| 24. |
- Ekstedt, M, et al.
(författare)
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Reply
- 2016
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Ingår i: Hepatology (Baltimore, Md.). - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 64:1, s. 310-311
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 25. |
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| 30. |
- Fischer, H, et al.
(författare)
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Dispositional pessimism and amygdala activity: a PET study in healthy volunteers
- 2001
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Ingår i: NEUROREPORT. - : LIPPINCOTT WILLIAMS & WILKINS. - 0959-4965. ; 12:8, s. 1635-1638
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Tidskriftsartikel (refereegranskat)abstract
- The present study used scores from Seligman's Attribution Style Questionnaire and [O-15] water positron emission tomographic measurements of regional cerebral blood flow (rCBF) to investigate the relation between individual differences in dispositional pe
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| 31. |
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| 33. |
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| 34. |
- Furmark, Tomas, et al.
(författare)
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Elevated uptake of [C-11] 5-hydroxy-tryptophan in the amygdala in patients with social anxiety disorder : a PET study
- 2009
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Ingår i: Biol. Psychiatry 65, 126S-127S. ; , s. 421-
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Social anxiety disorder (SAD) is associated with amygdala hyperresponsivity and imbalances in serotonergic neurotransmission. We have previously noted altered uptake of carbon-11 labelled 5-hydroxytryptophan (5-HTP) in a small sample of patients with SAD, suggesting deficiencies in presynaptic serotonin synthesis. In the present study, positron emission tomography (PET) was used to assess uptake of [11C]5-HTP in a larger sample of patients with SAD compared with age and sex-matched healthy controls. Methods: PET-data were available for 17 patients (8 females, age 33±8 years) diagnosed with SAD and for 17 healthy controls (9 females, age 35±10 years). Accumulation of the [11C]5-HTP tracer was assessed at Uppsala Imanet during 60 minutes in the resting state. Parametric images were generated using the graphical reference Patlak method assuming irreversible trapping of [11C]5-HTP from 11-60 minutes. Cerebellum was selected as reference region after correction for the decarboxylation rate of [11C]5-HTP. Exploratory and amygdala focused analyses were performed using statistical parametric mapping (SPM2). Results: Patients with SAD had significantly higher [11C]5-HTP uptake than controls in several regions including the superior, medial and inferior frontal gyrus, anterior cingulate cortex, hippocampus and lentiform nucleus, all in the left hemisphere. Region of interest analyses also revealed significantly higher uptake (SAD > controls) in the left (x-28 y-4 z-12; T=3.16) and right (x24 y1 z-15; T=2.82) amygdala (p<0.05 corrected). Conclusions: Higher [11C]5-HTP uptake, suggesting an elevated serotonin synthesis rate, was noted in patients with SAD compared to healthy controls predominantly in frontal and temporal regions including the amygdala.
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| 35. |
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| 36. |
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| 37. |
- Furmark, Tomas, et al.
(författare)
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Social phobia subtypes in the general population revealed by cluster analysis
- 2000
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Ingår i: Psychological Medicine. - 0033-2917 .- 1469-8978. ; 30:6, s. 1335-1344
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Tidskriftsartikel (refereegranskat)abstract
- Background. Epidemiological data on subtypes of social phobia are scarce and their defining features are debated. Hence, the present study explored the prevalence and descriptive characteristics of empirically derived social phobia subgroups in the general population. Methods. To reveal subtypes, data on social distress, functional impairment, number of social fears and criteria fulfilled for avoidant personality disorder were extracted from a previously published epidemiological study of 188 social phobics and entered into an hierarchical cluster analysis. Criterion validity was evaluated by comparing clusters on the Social Phobia Scale (SPS) and the Social Interaction Anxiety Scale (SIAS). Finally, profile analyses were performed in which clusters were compared on a set of sociodemographic and descriptive characteristics. Results. Three clusters emerged, consisting of phobics scoring either high (generalized subtype), intermediate (non-generalized subtype) or low (discrete subtype) on all variables. Point prevalence rates were 2.0%, 5.9% and 7.7% respectively. All subtypes were distinguished on both SPS and SIAS. Generalized or severe social phobia tended to be over-represented among individuals with low levels of educational attainment and social support. Overall, public-speaking was the most common fear. Conclusions. Although categorical distinctions may be used, the present data suggest that social phobia subtypes in the general population mainly differ dimensionally along a mild-moderate-severe continuum, and that the number of cases declines with increasing severity.
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| 38. |
- Furmark, T, et al.
(författare)
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Social phobia subtypes in the general population revealed by cluster analysis
- 2000
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Ingår i: PSYCHOLOGICAL MEDICINE. - : CAMBRIDGE UNIV PRESS. - 0033-2917. ; 30:6, s. 1335-1344
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Tidskriftsartikel (refereegranskat)abstract
- Background. Epidemiological data on subtypes of social phobia are scarce and their defining features are debated. Hence, the present study explored the prevalence and descriptive characteristics of empirically derived social phobia subgroups in the genera
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| 39. |
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| 40. |
- Gilbert, M. Thomas P., et al.
(författare)
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Whole-genome shotgun sequencing of mitochondria from ancient hair shafts
- 2007
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 317:5846, s. 1927-1930
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Tidskriftsartikel (refereegranskat)abstract
- Although the application of sequencing-by-synthesis techniques to DNA extracted from bones has revolutionized the study of ancient DNA, it has been plagued by large fractions of contaminating environmental DNA. The genetic analyses of hair shafts could be a solution: We present 10 previously unexamined Siberian mammoth (Mammuthus primigenius) mitochondrial genomes, sequenced with up to 48-fold coverage. The observed levels of damage-derived sequencing errors were lower than those observed in previously published frozen bone samples, even though one of the specimens was >50,000 14C years old and another had been stored for 200 years at room temperature. The method therefore sets the stage for molecular-genetic analysis of museum collections.
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| 41. |
- Goncalves, Isabel, et al.
(författare)
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Activator protein-1 in carotid plaques is related to cerebrovascular symptoms and cholesteryl ester content
- 2011
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Ingår i: Cardiovascular pathology. - : Elsevier. - 1054-8807 .- 1879-1336. ; 20:1, s. 36-43
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Tidskriftsartikel (refereegranskat)abstract
- Transcription factor activator protein-1 regulates genes involved in inflammation and repair. The aim of this study was to determine whether transcription factor activator protein-1 activity in carotid plaques is related to symptoms, lipid accumulation, or extracellular matrix composition. Methods: Twenty-eight atherosclerotic carotid plaques were removed by endarterectomy and divided into two groups based on the presence or absence of ipsilateral symptoms (b1 month ago). Activator protein-1 DNA binding activity was assessed, and subunit (c-Jun, JunD, JunB, c-Fos, FosB, Fra-1, Fra-2) protein levels analyzed by immunoblotting. Distribution of c-Jun in plaques was analyzed by immunohistochemistry. Results: Plaques associated with symptoms had increased activator protein-1 activity and increased expression of c-Jun and JunD, as compared to asymptomatic plaques. Fra-1 and Fra-2 were present in equal amounts in both groups, whereas JunB, FosB, and c-Fos were undetectable. Activator protein-1 activity correlated with cholesteryl ester and elastin in plaques and decreased with age. Activator protein-1 activity did not correlate with collagen, calcified tissue, or proteoglycan content. Conclusions: Activator protein-1 is increased in plaques associated with symptoms. The correlation between activator protein-1 and cholesteryl esters suggests that high activator protein-1 is a marker of plaque vulnerability. Activator protein-1 expression can also reflect the activation of repair processes.
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| 42. |
- Granberg, T, et al.
(författare)
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Clinical Feasibility of Synthetic MRI in Multiple Sclerosis : A Diagnostic and Volumetric Validation Study.
- 2016
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Ingår i: American Journal of Neuroradiology. - 0195-6108 .- 1936-959X. ; 37:6, s. 1023-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Quantitative MR imaging techniques are gaining interest as methods of reducing acquisition times while additionally providing robust measurements. This study aimed to implement a synthetic MR imaging method on a new scanner type and to compare its diagnostic accuracy and volumetry with conventional MR imaging in patients with MS and controls.MATERIALS AND METHODS: Twenty patients with MS and 20 healthy controls were enrolled after ethics approval and written informed consent. Synthetic MR imaging was implemented on a Siemens 3T scanner. Comparable conventional and synthetic proton-density-, T1-, and T2-weighted, and FLAIR images were acquired. Diagnostic accuracy, lesion detection, and artifacts were assessed by blinded neuroradiologic evaluation, and contrast-to-noise ratios, by manual tracing. Volumetry was performed with synthetic MR imaging, FreeSurfer, FMRIB Software Library, and Statistical Parametric Mapping. Repeatability was quantified by using the coefficient of variance.RESULTS: Synthetic proton-density-, T1-, and T2-weighted images were of sufficient or good quality and were acquired in 7% less time than with conventional MR imaging. Synthetic FLAIR images were degraded by artifacts. Lesion counts and volumes were higher in synthetic MR imaging due to differences in the contrast of dirty-appearing WM but did not affect the radiologic diagnostic classification or lesion topography (P = .50-.77). Synthetic MR imaging provided segmentations with the shortest processing time (16 seconds) and the lowest repeatability error for brain volume (0.14%), intracranial volume (0.12%), brain parenchymal fraction (0.14%), and GM fraction (0.56%).CONCLUSIONS: Synthetic MR imaging can be an alternative to conventional MR imaging for generating diagnostic proton-density-, T1-, and T2-weighted images in patients with MS and controls while additionally delivering fast and robust volumetric measurements suitable for MS studies.
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| 43. |
- Granqvist, P, et al.
(författare)
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Sensed presence and mystical experiences are predicted by suggestibility, not by the application of transcranial weak complex magnetic fields
- 2005
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Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940. ; 379:1, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Transcranial magnetic stimulation (TMS) with weak (micro Tesla) complex waveform fields have been claimed to evoke the sensed presence of a sentient being in up to 80% in the general population. These findings have had a questionable neurophysiological foundation as the fields are approximately six orders of magnitude weaker than ordinary TMS fields. Also, no independent replication has been reported. To replicate and extend previous findings, we performed a double-blind experiment (N = 89), with a sham-field control group. Personality characteristics indicating suggestibility (absorption, signs of abnormal temporal lobe activity, and a "new age"-life-style orientation) were used as predictors. Sensed presence, mystical, and other somatosensory experiences previously reported from the magnetic field stimulation were outcome measures. We found no evidence for any effects of the magnetic fields, neither in the entire group, nor in individuals high in suggestibility. Because the personality characteristics significantly predicted outcomes, suggestibility may account for previously reported effects. Our results strongly question the earlier claims of experiential effects of weak magnetic fields.
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