| 1. |
- Nordanstig, Annika, 1974, et al.
(författare)
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EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients (EVA-TRISP) registry: basis and methodology of a pan-European prospective ischaemic stroke revascularisation treatment registry.
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry.All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS).Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups.This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements.
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| 2. |
- Frazier-Wood, Alexis C., et al.
(författare)
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Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
- 2016
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Ingår i: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
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Tidskriftsartikel (refereegranskat)abstract
- Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
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| 3. |
- Smith, Jennifer A, et al.
(författare)
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Genome-wide association study identifies 74 loci associated with educational attainment
- 2016
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Ingår i: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542
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Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
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| 4. |
- Blomstrand, Peter, et al.
(författare)
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Pulsed tissue Doppler imaging for the detection of myocardial ischaemia, a comparison with myocardial perfusion SPECT
- 2004
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Ingår i: Clinical Physiology and Functional Imaging. - : John Wiley & Sons. - 1475-0961 .- 1475-097X. ; 24:5, s. 289-295
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Tidskriftsartikel (refereegranskat)abstract
- In order to compare the diagnostic ability of pulsed tissue Doppler and myocardial perfusion Single Photon Emission Computed Tomography (SPECT) in patients with a history of unstable coronary artery disease, CAD, 26 patients, 22 men and four women, age 47-76 years, were investigated in a prospective study, 5-10 day after an episode of unstable angina. Tissue Doppler and two-dimensional echocardiography were performed during dobutamine stress testing and myocardial scintigraphy after bicycle exercise and at rest. Patients with a normal SPECT had higher peak systolic velocity during dobutamine infusion, 18.9 ± 4.1 cm s-1, than patients with ischaemia, 12.2 ± 3.8 cm s-1 (P<0.001) or scar, 8.8 ± 3.0 cm s-1 (P<0.01). In a territorial analysis the difference in peak systolic velocity between areas with a normal and abnormal SPECT was less apparent. Failure to achieve ≥13 cm s-1 in mean-peak systolic velocity was the most accurate criterion for detection of significant CAD on SPECT. We conclude that pulsed tissue Doppler can be used for objective quantification of left ventricular wall motion during dobutamine stress testing and for identification of patients with CAD on SPECT but not for identification of regional ischaemia.
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| 5. |
- Kanter-Smoler, Gunilla, et al.
(författare)
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Novel findings in Swedish patients with MYH-associated polyposis: mutation detection and clinical characterization
- 2006
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Ingår i: Clin Gastroenterol Hepatol. - : Elsevier BV. - 1542-3565. ; 4:4, s. 499-506
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Biallelic mutations in the base-excision repair gene MYH have recently been associated with recessive inheritance of multiple colorectal adenomas. An investigation and characterization of MYH mutations in Swedish patients were therefore carried out. METHODS: A set of 15 unrelated adenomatous polyposis coli (APC)-mutation negative patients from the Swedish Polyposis Registry was screened for germline mutations in the MYH gene. The patients were clinically characterized and compared with 43 APC-mutation positive probands diagnosed during the same period. RESULTS: Disease-causing biallelic MYH mutations were identified in 6 patients (40%). The mean age at diagnosis was 47.8 years versus 34.1 years in APC-mutation positive patients (P = .015). Colorectal cancer at diagnosis of polyposis was present in 67% (4/6) of the patients, and all were right-sided, compared with only 19% versus 12.5% right-sided cancer in APC-mutation positive patients. Upper gastrointestinal manifestations were diagnosed in 1 of 5 compared with 23 of 27 in APC-mutation positive patients (odds ratio, 23; 95% confidence interval, 2-263; P = .0086). One family exhibited apparent dominant inheritance of colorectal adenomatous polyposis. Two new pathogenic mutations, MYH p.G175E and p.P391L, were identified. The mutations are argued to introduce profound changes in substrate-recognizing domains of the protein. CONCLUSIONS: Biallelic MYH mutations, including 2 novel mutations, were found in a substantial number of the patients with multiple colorectal adenomas who were negative for APC-mutation. The examined MYH-mutation positive patients were found to have higher risks of colorectal cancer at diagnosis, right-sided location of cancers, and a significantly lower incidence of upper gastrointestinal manifestations, compared with APC-mutation positive patients.
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| 6. |
- Karlsson, Karolina, 1975, et al.
(författare)
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Interventions for peri-implantitis and their effects on further bone loss: A retrospective analysis of a registry-based cohort
- 2019
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Ingår i: Journal of Clinical Periodontology. - : Wiley. - 0303-6979 .- 1600-051X. ; 46:8, s. 872-879
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Tidskriftsartikel (refereegranskat)abstract
- Objective The aim of the present study was to assess interventions and their consequences with regard to further bone loss at sites diagnosed with peri-implantitis. Materials and Methods In 2017, records of 70 patients diagnosed with moderate/severe peri-implantitis at >= 1 implant sites 4 years earlier were obtained. Changes of marginal bone levels during the study period assessed on radiographs and predictors of disease progression were identified by Cox regression and mixed linear modelling. Patient files were analysed for professional interventions related to the treatment of peri-implantitis. Results Mean bone loss (+/- SD) at implants diagnosed with moderate/severe peri-implantitis was 1.1 +/- 2.0 mm over the observation period of 3.3 years. While non-surgical measures including submucosal and/or supra-mucosal cleaning of implants were provided to almost all patients, surgical treatment of peri-implantitis was limited to a subgroup (17 subjects). Surgically treated implant sites demonstrated a mean bone loss of 1.4 +/- 2.4 mm prior to surgical intervention, while only minor changes (0.2 +/- 1.0 mm) occurred after therapy. Clinical parameters (bleeding/suppuration on probing and probing depth) assessed at diagnosis were statistically significant predictors of disease progression. Conclusions Non-surgical procedures were insufficient to prevent further bone loss at implant sites affected by moderate/severe peri-implantitis. Surgical treatment of peri-implantitis markedly diminished the progression of bone loss. Clinical assessments of bleeding on probing and probing depth at diagnosis predicted further bone loss.
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| 7. |
- Karlsson, Karolina, 1975, et al.
(författare)
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Technical complications following implant-supported restorative therapy performed in Sweden
- 2018
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Ingår i: Clinical Oral Implants Research. - : Wiley. - 0905-7161 .- 1600-0501. ; 29:6, s. 603-611
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveThe aim of this study was to evaluate the occurrence and consequences of technical complications in implant-supported restorative therapy. Material & MethodsThe occurrence and consequences of technical complications in implant-supported restorative therapy over a mean follow-up period of 5.3years were assessed based on documentation in files from 2,666 patients. Risk indicators were identified by the use of survival models, considering repeated events. Results were expressed as hazard ratios (HR) including 95% confidence intervals. ResultsTechnical complications occurred in 24.8% of the patients. Chipping and loss of retention were the most common, affecting 11.0% and 7.9% of supraconstructions, respectively, while implant-related complications (e.g., implant fracture) were rare. More than 50% of the affected patients experienced technical complications more than once and almost all reported complications led to interventions by a dental professional. The extent of the supraconstruction was the strongest risk indicator for both chipping (HR<0.2) and loss of retention (HR>3). ConclusionOver a 5-year period, technical complications in implant-supported restorative therapy occurred frequently and their management required professional intervention.
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| 8. |
- Balmes, Olivier, et al.
(författare)
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Cryo-TEM observation of 3-dimensionally ordered aggregates of 5-nm gold particles in organic solvents
- 2004
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Ingår i: Journal of Nanoparticle Research. - : Springer Science and Business Media LLC. - 1572-896X .- 1388-0764. ; 6:6, s. 569-576
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Tidskriftsartikel (refereegranskat)abstract
- In this article, we show evidence for the assembly of ordered 3-dimensional aggregates of 5-nm gold particles in toluene, 1-octanol, n-decane, and chloroform. The use of plunge-freezing allows to freeze the solution containing the aggregates at a rate which does not allow reorganisation of the particles during sample preparation. The samples were then observed using cryo-transmission electron microscopy (cryo-TEM) showing that most of the particles were part of ordered aggregates, thus proving that organisation already exists in solution. In some cases, the stability of the sample under the electron beam made it possible to record several pictures of the same aggregate at different angles and build animated tilt series.
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| 9. |
- Balmes, Olivier, et al.
(författare)
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Imaging atomic structure in metal nanoparticles using high-resolution cryo-TEM
- 2006
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Ingår i: Microscopy and Microanalysis. - 1435-8115. ; 12:2, s. 145-150
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Tidskriftsartikel (refereegranskat)abstract
- It has been shown, by imaging gold (200) planes, that it is possible to achieve better than 0.20-nm structural resolution in cryo-transmission electron microscopy (cryo-TEM). This has been done using commercially available cryo equipment and using a 300-kV field emission gun (FEG) TEM. The images of 15-nm gold particles embedded in amorphous frozen water clearly show the (111) planes (separated by 0.235 nm) in gold. Fourier transform demonstrates the presence of (200) planes in the image, proving a resolution of better than 0.20 nm. The experimental results are Supported by image simulations using the multislice method. These simulations suggest that it should be possible to achieve the same resolution even in smaller particles and particles of lighter elements. The crucial experimental problem to overcome is keeping the thickness of the amorphous film low and to work at low electron dose conditions.
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| 10. |
- Berglund, Erik, et al.
(författare)
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Intracellular concentration of the tyrosine kinase inhibitor imatinib in gastrointestinal stromal tumor cells.
- 2014
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Ingår i: Anti-Cancer Drugs. - 0959-4973 .- 1473-5741. ; 25:4, s. 415-22
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Tidskriftsartikel (refereegranskat)abstract
- Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm in the gastrointestinal tract. In most GISTs, the underlying mechanism is a gain-of-function mutation in the KIT or the PDGFRA gene. Imatinib is a tyrosine kinase inhibitor that specifically blocks the intracellular ATP-binding sites of these receptors. A correlation exists between plasma levels of imatinib and progression-free survival, but it is not known whether the plasma concentration correlates with the intracellular drug concentration. We determined intracellular imatinib levels in two GIST cell lines: the imatinib-sensitive GIST882 and the imatinib-resistant GIST48. After exposing the GIST cells to imatinib, the intracellular concentrations were evaluated using LC-MS (TOF). The concentration of imatinib in clinical samples from three patients was also determined to assess the validity and reliability of the method in the clinical setting. Determination of imatinib uptake fits within detection levels and values are highly reproducible. The GIST48 cells showed significantly lower imatinib uptake compared with GIST882 in therapeutic doses, indicating a possible difference in uptake mechanisms. Furthermore, imatinib accumulated in the tumor tissues and showed intratumoral regional differences. These data show, for the first time, a feasible and reproducible technique to measure intracellular imatinib levels in experimental and clinical settings. The difference in the intracellular imatinib concentration between the cell lines and clinical samples indicates that drug transporters may contribute toward resistance mechanisms in GIST cells. This highlights the importance of further clinical studies to quantify drug transporter expression and measure intracellular imatinib levels in GIST patients.
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