| 1. |
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| 2. |
- Erlinge, D., et al.
(författare)
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Bivalirudin versus Heparin Monotherapy in Myocardial Infarction
- 2017
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 377:12, s. 1132-1142
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Tidskriftsartikel (refereegranskat)abstract
- Background The comparative efficacy of various anticoagulation strategies has not been clearly established in patients with acute myocardial infarction who are undergoing percutaneous coronary intervention (PCI) according to current practice, which includes the use of radial-artery access for PCI and administration of potent P2Y12 inhibitors without the planned use of glycoprotein IIb/IIIa inhibitors. Methods In this multicenter, randomized, registry-based, open-label clinical trial, we enrolled patients with either ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) who were undergoing PCI and receiving treatment with a potent P2Y12 inhibitor (ticagrelor, prasugrel, or cangrelor) without the planned use of glycoprotein IIb/IIIa inhibitors. The patients were randomly assigned to receive bivalirudin or heparin during PCI, which was performed predominantly with the use of radial-artery access. The primary end point was a composite of death from any cause, myocardial infarction, or major bleeding during 180 days of follow-up. Results A total of 6006 patients (3005 with STEMI and 3001 with NSTEMI) were enrolled in the trial. At 180 days, a primary end-point event had occurred in 12.3% of the patients (369 of 3004) in the bivalirudin group and in 12.8% (383 of 3002) in the heparin group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.10; P=0.54). The results were consistent between patients with STEMI and those with NSTEMI and across other major subgroups. Myocardial infarction occurred in 2.0% of the patients in the bivalirudin group and in 2.4% in the heparin group (hazard ratio, 0.84; 95% CI, 0.60 to 1.19; P=0.33), major bleeding in 8.6% and 8.6%, respectively (hazard ratio, 1.00; 95% CI, 0.84 to 1.19; P=0.98), definite stent thrombosis in 0.4% and 0.7%, respectively (hazard ratio, 0.54; 95% CI, 0.27 to 1.10; P=0.09), and death in 2.9% and 2.8%, respectively (hazard ratio, 1.05; 95% CI, 0.78 to 1.41; P=0.76). Conclusions Among patients undergoing PCI for myocardial infarction, the rate of the composite of death from any cause, myocardial infarction, or major bleeding was not lower among those who received bivalirudin than among those who received heparin monotherapy. (Funded by the Swedish Heart-Lung Foundation and others; VALIDATE-SWEDEHEART ClinicalTrialsRegister.eu number, 2012-005260-10 ; ClinicalTrials.gov number, NCT02311231 .).
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| 3. |
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| 4. |
- Nilsson, Tina, et al.
(författare)
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An induced pluripotent stem cell t(7;12)(q36;p13) acute myeloid leukemia model shows high expression of MNX1 and a block in differentiation of the erythroid and megakaryocytic lineages
- 2022
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 151:5, s. 770-782
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Tidskriftsartikel (refereegranskat)abstract
- Acute myeloid leukemia (AML) results from aberrant hematopoietic processes and these changes are frequently initiated by chromosomal translocations. One particular subtype, AML with translocation t(7;12)(q36;p13), is found in children diagnosed before 2 years of age. The mechanisms for leukemogenesis induced by t(7;12) is not understood, in part because of the lack of efficient methods to reconstruct the leukemia-associated genetic aberration with correct genomic architecture and regulatory elements. We therefore created induced pluripotent stem cell (iPSC) lines that carry the translocation t(7;12) using CRISPR/Cas9. These t(7;12) iPSC showed propensity to differentiate into all three germ layers, confirming retained stem cell properties. The potential for differentiation into hematopoietic stem and progenitor cells (HSPC) was shown by expression of CD34, CD43 and CD45. Compared with the parental iPSC line, a significant decrease in cells expressing CD235a and CD41a was seen in the t(7;12) iPSC-derived HSPC (iHSPC), suggesting a block in differentiation. Moreover, colony formation assay showed an accumulation of cells at the erythroid and myeloid progenitor stages. Gene expression analysis revealed significant down-regulation of genes associated with megakaryocyte differentiation and up-regulation of genes associated with myeloid pathways but also genes typically seen in AML cases with t(7;12). Thus, this iPSC t(7;12) leukemia model of the t(7;12) AML subtype constitutes a valuable tool for further studies of the mechanisms for leukemia development and to find new treatment options.
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| 5. |
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| 6. |
- Almuzzaini, Bader, et al.
(författare)
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In beta-actin knockouts, epigenetic reprogramming and rDNA transcription inactivation lead to growth and proliferation defects
- 2016
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Ingår i: The FASEB Journal. - 0892-6638 .- 1530-6860. ; 30:8, s. 2860-2873
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Tidskriftsartikel (refereegranskat)abstract
- Actin and nuclear myosin 1 (NM1) are regulators of transcription and chromatin organization. Using a genome-wide approach, we report here that beta-actin binds intergenic and genic regions across the mammalian genome, associated with both protein-coding and rRNA genes. Within the rDNA, the distribution of beta-actin correlated with NM1 and the other subunits of the B-WICH complex, WSTF and SNF2h. In beta-actin(-/-) mouse embryonic fibroblasts (MEFs), we found that rRNA synthesis levels decreased concomitantly with drops in RNA polymerase I (Pol I) and NM1 occupancies across the rRNA gene. Reintroduction of wild-type beta-actin, in contrast to mutated forms with polymerization defects, efficiently rescued rRNA synthesis underscoring the direct role for a polymerization-competent form of beta-actin in Pol I transcription. The rRNA synthesis defects in the beta-actin(-/-) MEFs are a consequence of epigenetic reprogramming with up-regulation of the repressive mark H3K4me1 (mono-methylation of lys4 on histone H3) and enhanced chromatin compaction at promoter-proximal enhancer (T0 sequence), which disturb binding of the transcription factor TTF1. We propose a novel genome-wide mechanism where the polymerase-associated beta-actin synergizes with NM1 to coordinate permissive chromatin with Pol I transcription, cell growth, and proliferation.
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| 7. |
- Astvaldsdottir, A., et al.
(författare)
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Oral health and dental care of older persons-A systematic map of systematic reviews
- 2018
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Ingår i: Gerodontology. - : Wiley. - 0734-0664 .- 1741-2358. ; 35:4, s. 290-304
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Forskningsöversikt (refereegranskat)abstract
- Objectives: To examine the current knowledge on oral health status and dental care of older persons through a systematic mapping of systematic reviews of low or moderate risk of bias. Background: Geriatric dentistry covers all aspects of oral health and oral care of older persons. Oral health is part of general health and contributes to a person's physical, psychological and social wellbeing. Methods: A literature search was performed in three different databases (PubMed, The Cochrane Library and Cinahl) within 12 domains: Dental caries, periodontitis, Orofacial pain and temporomandibular joint (TMJ) pain, mucosal lesions, oral motor function, dry mouth, halitosis, interaction between oral status and other medical conditions, ability to interrelate and communicate, quality of life, ethics and organisation of dental care for older persons. Systematic reviews were identified and scrutinised, highlighting scientific knowledge and knowledge gaps. Results: We included 32 systematic reviews of which 14 were judged to be of low/moderate risk of bias. Most of the domains lack systematic reviews with low or moderate risk of bias. In two of the domains evidence was identified; in institutionalised people aged 65 or older, effective oral hygiene can prevent pneumonia. Furthermore, there is an evidence of a relationship between malnutrition (protein energy-related malnutrition, PEM) and poor appetite and edentulousness. Conclusions: There is an urgent need for further research and evidence-based knowledge within most domains in geriatric dentistry and in other fields related to oral health and dental care for older persons striving for multi-disciplinary research programmes.
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| 8. |
- Barbier, Christophe, 1974-, et al.
(författare)
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Experimental investigation of damage at folding of coated papers
- 2002
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Ingår i: Nordic Pulp & Paper Research Journal. - Sundsvall : Mittuniversitetet. - 0283-2631 .- 2000-0669. ; 17:1, s. 34-
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Tidskriftsartikel (refereegranskat)abstract
- To achieve a better understanding of the folding properties of coated papers pertinent to the mechanical behaviour, a microscopic investigation was performed. The influence on the damage levels in the coating from such features as delamination, humidity and paper thickness have been studied
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| 9. |
- Barbier, Christophe, et al.
(författare)
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Folding of printed papers: experiments and numerical analysis
- 2003
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Konferensbidrag (populärvet., debatt m.m.)abstract
- Folding of digital prints has been investigated experimentally in order to determine the influence from different features on the residual strength of the folded paper. In particular, the effect of toner-layer, paper-fibre orientation and pre-creasing is investigated and the experimental results are supplemented with numerical ones based on the finite element method. The results indicate that creasing, and to a less extend also fibre orientation, is the most important factor influencing the residual tensile strength after folding
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| 10. |
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| 11. |
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| 12. |
- Börjesson, Stefan, 1979-, et al.
(författare)
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Detection of an IMI-2 carbapenemase-producing Enterobacter asburiae at a Swedish feed mill
- 2022
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Ingår i: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Occurrence of multidrug resistant Enterobacteriaceae in livestock is of concern as they can spread to humans. A potential introduction route for these bacteria to livestock could be animal feed. We therefore wanted to identify if Escherichia spp., Enterobacter spp., Klebsiella spp., or Raoutella spp. with transferable resistance to extended spectrum cephalosporins, carbapenems or colistin could be detected in the environment at feed mills in Sweden. A second aim was to compare detected isolates to previous described isolates from humans and animals in Sweden to establish relatedness which could indicate a potential transmission between sectors and feed mills as a source for antibiotic resistant bacteria. However, no isolates with transferable resistance to extended-cephalosporins or colistin could be identified, but one isolate belonging to the Enterobacter cloacae complex was shown to be carbapenem-resistant and showing carbapenemase-activity. Based on sequencing by both short-read Illumina and long-read Oxford Nanopore MinIon technologies it was shown that this isolate was an E. asburiae carrying a bla IMI-2 gene on a 216 Kbp plasmid, designated pSB89A/IMI-2, and contained the plasmid replicons IncFII, IncFIB, and a third replicon showing highest similarity to the IncFII(Yp). In addition, the plasmid contained genes for various functions such as plasmid segregation and stability, plasmid transfer and arsenical transport, but no additional antibiotic resistance genes. This isolate and the pSB89A/IMI-2 was compared to three human clinical isolates positive for bla IMI-2 available from the Swedish antibiotic monitoring program Swedres. It was shown that one of the human isolates carried a plasmid similar with regards to gene content to the pSB89A/IMI-2 except for the plasmid transfer system, but that the order of genes was different. The pSB89A/IMI-2 did however share the same transfer system as the bla IMI-2 carrying plasmids from the other two human isolates. The pSB89A/IMI-2 was also compared to previously published plasmids carrying bla IMI-2, but no identical plasmids could be identified. However, most shared part of the plasmid transfer system and DNA replication genes, and the bla IMI-2 gene was located next the transcription regulator imiR. The IS3-family insertion element downstream of imiR in the pSB89A was also related to the IS elements in other bla IMI-carrying plasmids.
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| 13. |
- Coradeschi, Silvia, et al.
(författare)
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GiraffPlus : A System for Monitoring Activities and Physiological Parameters and Promoting Social Interaction for Elderly
- 2014
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Ingår i: Human-Computer Systems Interaction. - Cham : Springer. - 2194-5357. - 9783319084909 - 9783319084916 ; , s. 261-271
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Bokkapitel (refereegranskat)abstract
- This chapter presents a telehealth system called GiraffPlus supporting independent living of elderly in their own home. GiraffPlus system is a complex system which monitors activities and physiological parameters in the home using a network of sensors. The elaborated information is presented to the primary user, the elderly, and to secondary users like health care and home care providers and possibly to family members as a help to assess possible health and wellbeing deterioration, provide acute alarms, and support health procedure. The secondary users can also visit the elderly via the Giraff, a teleoperated robot that can communicate and move in the home under the control of the secondary user. The chapter focusses in particular on the deployment of the system in six real homes in Sweden, Italy and Spain. The chapter outlines the technological various components used, the expectations of the users and the evaluation method.
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| 14. |
- Crawley, E. F., et al.
(författare)
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Curriculum design based on the CDIO model
- 2005
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Ingår i: SEFI 2005 Annual Conference. - : Middle East Technical University, Faculty of Engineering. - 9789754292367 ; , s. 184-191
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Konferensbidrag (refereegranskat)abstract
- Implement-Operate (CDIO) engineering educational strategy has been adopted by a number of universities as a framework for reforming engineering programs. One of the key activities in CDIO adoption and implementation is designing the engineering curriculum to integrate personal, interpersonal and system-building learning outcomes into the curriculum. This paper details approaches and experiences from curriculum design efforts at MIT, KTH, and Chalmers.
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| 15. |
- Dominic, Chris A. S., et al.
(författare)
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Towards a conceptual sustainable packaging development model : A corrugated box case study
- 2015
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Ingår i: Packaging technology & science. - New York : Wiley. - 0894-3214 .- 1099-1522. ; 28:5, s. 397-413
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Tidskriftsartikel (refereegranskat)abstract
- Corrugated package designers are focused on balancing the need for product protection, material use efficiency and the packaging material's impact on the environment in the supply chain. The purpose of this paper is to develop a conceptual sustainable packaging model that integrates the variables of technical design, supply chain systems and environmental factors and then use the model to identify to improve upon corrugated container design. A model was developed, from the extant literature, and a case study was performed on a corrugated container. This is believed to be a unique integrated model of most relevant agents related to the design and implementation of a corrugated box through a supply chain from design to potential post-consumer reuse. From this study, we found opportunities to improve the environmental design of the corrugated container through four ex ante design stages, and two ex post facto supply chain stages. Further, research can evaluate and refine this model via a 'live supply chain' for use in guiding corrugated box material selection design and reuse/recycling. Integration of the design criterion for a unit load in the supply chain creates opportunity to observe the packaging system holistically. Waste in the manufacturing process and CO2 emissions are traced along the material flow until the end of its useful life to provide an overall picture of the packaging system.
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| 16. |
- Ericsson, T S, et al.
(författare)
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History and forest biodiversity of woodland key habitats in south boreal Sweden
- 2005
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Ingår i: Biological Conservation. - : Elsevier BV. - 0006-3207 .- 1873-2917. ; 122:2, s. 289-303
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Tidskriftsartikel (refereegranskat)abstract
- Forest exploitation has destructed forest habitats in Fermoscandia during last centuries. Vital components of existing forest biodiversity have been identified as small (a few ha) woodland key habitats (WKHs). Many WKHs in boreal forest landscapes are assumed to represent remnant near-natural forests from before the phase of industrial forest exploitation. Thus, WKHs are supposed to (i) exhibit a low degree of exploitation, (ii) have old-growth characteristics and (iii) host Red-list species. Yet, WKHs' history and biodiversity have not been systematically investigated. Thus, their conservation values remain unclear. This study investigates history and biodiversity of 15 WKHs in central Sweden with retrospective methods and field studies. We analyze (1) forest structure before, during and after the forest exploitation period, (2) existing biodiversity, i.e. species and structural elements, and (3) to what extent human activities (forestry) have influenced current biodiversity. Our results indicate that forest structure within the areas that currently are classified as WKHs has changed dramatically since the mid-19th century, when forests were unaffected by logging. The results suggest that fire-suppression during last century, gradually increased logging until mid-20th century and abandonment by modern forestry during the late 20th century, are main causes behind this transformation. Less than 10% of studied WKHs had biological features that resembled those of pristine boreal forests. Thus, most studied WKHs cannot be classified as near-natural or remnants of pristine forest. We Suggest that the program for WKHs give more focus to pre-industrial forest structure, local historical aspects being seriously regarded and ecological restoration efforts being introduced.
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| 17. |
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| 18. |
- Esteves, Cláudia S. V. G., 1989-, et al.
(författare)
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Evaluating the Potential to Modify Pulp and Paper Properties through Oxygen Delignification
- 2020
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Ingår i: ACS Omega. - : American Chemical Society (ACS). - 2470-1343. ; 5:23, s. 13703-13711
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Tidskriftsartikel (refereegranskat)abstract
- The potential to modify pulp and paper properties by oxygen delignification was assessed by looking beyond the ordinary purpose of oxygen delignification. Pulps with the same kappa number were obtained by both pulping and the combination of pulping and oxygen delignification, and the mechanical and chemical properties were compared. The oxidation of pulp components leads to an increase in carboxylic acid groups in the fibers, resulting in a large influence on fiber swelling, seen as an increase in the water retention value and fiber saturation point. The introduction of charged groups appears to replace some of the morphological changes caused by refining and enhance the strength of fiber–fiber joints, generating pulps with better refinability and higher tensile strength. Oxygen delignification was able to improve the tensile index with 6% at the same sheet density and less refining energy, when the amount of total fiber charges was higher than 140 μekv/g.
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| 19. |
- Fadl, Helena E., 1965-, et al.
(författare)
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Maternal and neonatal outcomes and time trends of gestational diabetes mellitus in Sweden from 1991 to2003
- 2010
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Ingår i: Diabetic Medicine. - Malden 02148, MA USA : Wiley-Blackwell. - 0742-3071 .- 1464-5491. ; 27:4, s. 436-441
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Tidskriftsartikel (refereegranskat)abstract
- Aims To determine maternal and neonatal outcomes for women with gestational diabetes mellitus (GDM) in Sweden during 1991–2003, and to compare the outcomes in the two time periods.Methods This is a population-based cohort study using the Swedish Medical Birth Register data for the period 1991–2003. There were 1 260 297 women with singleton pregnancies registered during this time, of whom 10 525 were diagnosed with GDM, based on a 75 g oral glucose tolerance test. The main diagnostic criteria were fasting capillary whole blood glucose ≥ 6.1 mmol⁄l and 2 h blood glucose ≥ 9.0 mmol⁄l.Results Maternal characteristics differed significantly between the GDM and non-GDM group. Adjusted odds ratios (OR) were as follows: for pre-eclampsia, 1.81 (95% confidence interval (CI) 1.64–2.00); for shoulder dystocia, 2.74 (2.04–3.68); and for Caesarean section, 1.46 (1.38–1.54).No difference was seen in perinatal mortality, stillbirth rates, Apgar scores, fetal distress or transient tachypnoea. There was a markedly higher risk of large for gestational age,OR3.43 (3.21–3.67), and Erb’s palsy, OR 2.56 (1.96–3.32), in the GDMgroup, and statistically significant differences in prematurity < 37 weeks, birthweight > 4.5 kg, and major malformation, OR 1.19–1.71. No statistically significant improvement in outcomes was seen between the two study periods.Conclusions Women with GDM have higher risks of pre-eclampsia, shoulder dystocia and Caesarean section. Their infants are often large for gestational age and have higher risks of prematurity, Erb’s palsy and major malformations. These outcomes did not improve over time.
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| 20. |
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| 21. |
- Fadl, Helena E., 1965-, et al.
(författare)
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Randomized controlled study in pregnancy on treatment of marked hyperglycemia that is short of overt diabetes
- 2015
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley-Blackwell. - 0001-6349 .- 1600-0412. ; 94:11, s. 1181-1187
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: A randomized multicenter study was conducted in the Stockholm-orebro areas in Sweden to evaluate how treatment aiming at normoglycemia affects fetal growth, pregnancy and neonatal outcome in pregnant women with severe hyperglycemia.Material and methods: Pregnant women with hyperglycemia defined as fasting capillary plasma glucose <7.0 mmol/L and a two-hour plasma glucose value 10.0 and <12.2 mmol/L following a 75-g oral glucose tolerance test (OGTT) diagnosed before 34 weeks of gestation were randomized to treatment (n=33) or controls (n=36). Women assigned to the control group were blinded for the OGTT results and received routine care. The therapeutic goal was fasting plasma glucose 4-5 mmol/L, and <6.5 mmol/L after a meal. Primary outcomes were size at birth and number of large-for-gestational age (>90th percentile) neonates. Secondary outcomes were pregnancy complications, neonatal morbidity and glycemic control.Results: The planned number of participating women was not reached. There was a significantly reduced rate of large-for-gestational age neonates, 21 vs. 47%, P<0.05. Group differences in pregnancy complications and neonatal morbidity were not detected because of limited statistical power. In total, 66.7% of the women in the intervention group received insulin. Of all measured plasma glucose values, 64.1% were in the target range, 7.2% in the hypoglycemic range and 28.7% above target values. There were no cases of severe hypoglycemia.Conclusions: Aiming for normalized glycemia in a pregnancy complicated by severe hyperglycemia reduces fetal growth but is associated with an increased rate of mild hypoglycemia.
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| 22. |
- Fernández-Ardèvol, M., et al.
(författare)
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Methodological Strategies to Understand Smartphone Practices for Social Connectedness in Later Life
- 2019
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Ingår i: Proceedings 5th International Conference on Human Aspects of IT for the Aged Population, ITAP 2019, held as part of the 21st International Conference on Human-Computer Interaction, HCI International 2019. - Cham : Springer Verlag. - 9783030220143 ; , s. 46-64
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Konferensbidrag (refereegranskat)abstract
- Digital practices in later life are not yet well understood. Therefore, this paper discusses the framework for a research design project that aims at tracing differences and similarities in how older adults use their smartphones in circumstances in and outside their homes in Spain, the Netherlands, Sweden, and Canada. The research questions of this international research project focus on the extent to which digital mobile practices relate to perceived social connectedness among older adults aged 55–79 years old. While studies have shown that the subjective experience of ‘being connected’ supports continued wellbeing in later life, there remains an insufficient understanding of the processes through which digital mediated social interaction is effective for social connectedness. The analytical framework of the project prioritizes the co-constituency of (digital) technology and ageing, and takes digital practices in everyday life as its entry point. The main data collection tool will be the tracking of smartphone activity of 600 older adults (150 per country) during four weeks. An online survey and qualitative interviews will gather data about the meanings of the quantified digital practices, and how they shape (if they do) the participants’ connection to the world. This approach will allow us not only to get insight into what older adults say how they used their smartphone but also to gain insight into their real-life daily use. The assessment of the challenges, strengths, and weaknesses of the methods contributes towards an accurate and appropriate interpretation of empirical results and their implications.
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| 23. |
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| 24. |
- Gronlund, C., et al.
(författare)
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Simultaneous estimation of muscle fibre conduction velocity and muscle fibre orientation using 2D multichannel surface electromyogram
- 2005
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Ingår i: Medical and Biological Engineering and Computing. - 0140-0118 .- 1741-0444. ; 43:1, s. 63-70
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Tidskriftsartikel (refereegranskat)abstract
- The paper presents a new approach for simultaneous estimation of muscle fibre conduction velocity (MFCV) and muscle fibre orientation (MFO) for motor units (MUs) in two-dimensional (2D) multichannel surface electromyography recordings. This is an important tool for detecting changes and abnormalities in muscle function and structure. In addition, simultaneous estimation of MFO and MFCV avoids the necessity of manual electrode alignment. The proposed method detected propagating MU action potentials (MUAPs) in a running time window as moving components in amplitude maps. Thereafter, estimations were obtained by fitting a three-dimensional function to these maps. The performance was evaluated using synthetic MU signals at 10 dB SNR and authentic biceps brachii measurements. Results demonstrated MFCV and MFO estimates with standard deviations of less than 0.05 m s-1 and 1° for simulated signals, and less than 0.2 m s-1 and 4° for experimental data. However, standard deviations as low as 0.12 m s-1 and 1.6° from real signals were demonstrated. It was concluded that the method performs as well as, or better than, linear array multichannel methods when individual propagating MUAPs can be identified, even if electrodes are not aligned with fibre direction. © IFMBE 2005.
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| 25. |
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| 26. |
- Held, Claes, 1956-, et al.
(författare)
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Inflammatory Biomarkers Interleukin-6 and C-Reactive Protein and Outcomes in Stable Coronary Heart Disease : Experiences From the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) Trial
- 2017
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 6:10
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundEvaluation of cardiovascular prognosis in patients with stable coronary heart disease is based on clinical characteristics and biomarkers indicating dysglycemia, dyslipidemia, renal dysfunction, and possibly cardiac dysfunction. Inflammation plays a key role in atherosclerosis, but the association between inflammatory biomarkers and clinical outcomes is less studied in this population.Methods and ResultsOverall, 15 828 patients with coronary heart disease in the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial werer and randomized to treatment with darapladib or placebo and observed for a median of 3.7 years. In 14 611 patients, levels of interleukin-6 (IL-6) and high-sensitivity C-reactive protein were measured in plasma samples: median levels were2.1 (interquartile range, 1.4-3.2) ng/Land1.3 (interquartile range, 0.6-3.1) mg/L, respectively. Associations between continuous levels or quartile groups and adjudicated outcomes were evaluated by spline graphs and Cox regression adjusted for clinical factors and cardiovascular biomarkers. IL-6 was associated with increased risk of major adverse cardiovascular events (quartile 4 versus quartile 1 hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.30-1.97; P< 0.0001); cardiovascular death (HR, 2.15; 95% CI, 1.53-3.04; P< 0.0001); myocardial infarction (HR, 1.53; 95% CI, 1.14-2.04; P< 0.05); all-cause mortality (HR, 2.11; 95% CI, 1.62-2.76; P< 0.0001); and risk of hospitalization for heart failure (HR, 2.28; 95% CI, 1.34-3.89; P< 0.001). Cancer death was doubled in the highest IL-6 quartile group (HR, 2.34; 95% CI, 1.20-4.53; P< 0.05). High-sensitivity C-reactive protein was associated with both cardiovascular and non-cardiovascular events in the unadjusted model, but these did not remain after multivariable adjustments.ConclusionsIL-6, an upstream inflammatory marker, was independently associated with the risk of major adverse cardiovascular events, cardiovascular and all-cause mortality, myocardial infarction, heart failure, and cancer mortality in patients with stable coronary heart disease. IL-6 might reflect a pathophysiological process involved in the development of these events.
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| 27. |
- Hirn, Ulrich, et al.
(författare)
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The Area of Molecular Contact in Fiber-Fiber Bonds
- 2013
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Ingår i: Advances in Pulp and Paper Reserach, Cambridge 2013. - 9780992616304 ; , s. 201-223
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Konferensbidrag (refereegranskat)abstract
- We are presenting a coherent theoretical concept as well as empirical evidence suggesting that there is a high degree of molecular contact in fiberfiber bonds, the surfaces might even be in full contact.Fundamental theoretical relations from contact mechanics governing the area in molecular contact between surfaces are reviewed and proposed for the quantitative analysis of the area in molecular contact in fiber-fiber bonds.The key parameters determining the degree of molecular contact according to the theory are indentation hardness and elastic modulus of the wet pulp fibers, surface roughness of the wet fibers and the pressure applied to the fiber bonds during bond formation.We provide results for fiber indentation hardness and effective elastic modulus from nanoindentation measurements of fiber surfaces at varying relative humidity and in water. The fiber surface properties have been determined with an atomic force microscopy technique specifically designed to measure soft, viscoelastic materials. Also, surface roughness has been measured in the wet and dry state.Experiments with individual fiber-fiber joints show that the breaking strength of these joints is independent from the pressure during bond formation indicating that the surfaces in fiber-fiber bonds are in a high degree of molecular contact, maybe even full contact. This is the case even if they are formed without external pressure. Computer simulations of the degree of mechanical contact of fiber surfaces during drying were performed indicating that capillary adhesion is pulling the fiber surfaces into a high degree of molecular contact. These findings are discussed with respect to the literature considering FRET microscopy and Transmission Electron Microscopy of fiber-fiber bonds.
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| 28. |
- Hultcrantz, Monica, et al.
(författare)
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The GRADE Working Group clarifies the construct of certainty of evidence
- 2017
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Ingår i: Journal of Clinical Epidemiology. - : Pergamon Press. - 0895-4356 .- 1878-5921. ; 87, s. 4-13
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To clarify the grading of recommendations assessment, development and evaluation (GRADE) definition of certainty of evidence and suggest possible approaches to rating certainty of the evidence for systematic reviews, health technology assessments, and guidelines. Study Design and Setting: This work was carried out by a project group within the GRADE Working Group, through brainstorming and iterative refinement of ideas, using input from workshops, presentations, and discussions at GRADE Working Group meetings to produce this document, which constitutes official GRADE guidance. Results: Certainty of evidence is best considered as the certainty that a true effect lies on one side of a specified threshold or within a chosen range. We define possible approaches for choosing threshold or range. For guidelines, what we call a fully contextualized approach requires simultaneously considering all critical outcomes and their relative value. Less-contextualized approaches, more appropriate for systematic reviews and health technology assessments, include using specified ranges of magnitude of effect, for example, ranges of what we might consider no effect, trivial, small, moderate, or large effects. Conclusion: It is desirable for systematic review authors, guideline panelists, and health technology assessors to specify the threshold or ranges they are using when rating the certainty in evidence. (C) 2017 The Authors. Published by Elsevier Inc.
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| 29. |
- Häggman Henrikson, Birgitta, et al.
(författare)
-
Pharmacological treatment of oro-facial pain : health technology assessment including a systematic review with network meta-analysis
- 2017
-
Ingår i: Journal of Oral Rehabilitation. - Hoboken : John Wiley & Sons. - 1365-2842 .- 0305-182X. ; 44:10, s. 800-826
-
Forskningsöversikt (refereegranskat)abstract
- This health technology assessment evaluated the efficacy of pharmacological treatment in patients with oro-facial pain. Randomised controlled trials were included if they reported pharmacological treatment in patients >= 18 years with chronic (>= 3 months) oro-facial pain. Patients were divided into subgroups: TMD-muscle [ temporomandibular disorders (TMD) mainly associated with myalgia]; TMD-joint (TMD mainly associated with temporomandibular joint pain); and burning mouth syndrome (BMS). The primary outcome was pain intensity reduction after pharmacological treatment. The scientific quality of the evidence was rated according to GRADE. An electronic search in PubMed, Cochrane Library, and EMBASE from database inception to 1 March 2017 combined with a handsearch identified 1552 articles. After screening of abstracts, 178 articles were reviewed in full text and 57 studies met the inclusion criteria. After risk of bias assessment, 41 articles remained: 15 studies on 790 patients classified as TMD-joint, nine on 375 patients classified as TMD-muscle and 17 on 868 patients with BMS. Of these, eight studies on TMD-muscle, and five on BMS were included in separate network meta-analysis. The narrative synthesis suggests that NSAIDs as well as corticosteroid and hyaluronate injections are effective treatments for TMD-joint pain. The network meta-analysis showed that clonazepam and capsaicin reduced pain intensity in BMS, and the muscle relaxant cyclobenzaprine, for the TMD-muscle group. In conclusion, based on a limited number of studies, evidence provided with network meta-analysis showed that clonazepam and capsaicin are effective in treatment of BMS and that the muscle relaxant cyclobenzaprine has a positive treatment effect for TMD-muscle pain.
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| 30. |
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| 31. |
- Karlsson, J.S, et al.
(författare)
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An estimation of the influence of force decrease on the mean power spectral frequency shift of the EMG during repetitive maximum dynamic knee extensions
- 2003
-
Ingår i: Journal of Electromyography & Kinesiology. - 1050-6411 .- 1873-5711. ; 13:5, s. 461-468
-
Tidskriftsartikel (refereegranskat)abstract
- Frequency analysis of myoelectric (ME) signals, using the mean power spectral frequency (MNF), has been widely used to characterize peripheral muscle fatigue during isometric contractions assuming constant force. However, during repetitive isokinetic contractions performed with maximum effort, output (force or torque) will decrease markedly during the initial 40-60 contractions, followed by a phase with little or no change. MNF shows a similar pattern. In situations where there exist a significant relationship between MNF and output, part of the decrease in MNF may per se be related to the decrease in force during dynamic contractions. This study estimated force effects on the MNF shifts during repetitive dynamic knee extensions. Twenty healthy volunteers participated in the study and both surface ME signals (from the right vastus lateralis, vastus medialis, and rectus femoris muscles) and the biomechanical signals (force, position, and velocity) of an isokinetic dynamometer were measured. Two tests were performed: (i) 100 repetitive maximum isokinetic contractions of the right knee extensors, and (ii) five gradually increasing static knee extensions before and after (i). The corresponding ME signal time-frequency representations were calculated using the continuous wavelet transform. Compensation of the MNF variables of the repetitive contractions was performed with respect to the individual MNF-force relation based on an average of five gradually increasing contractions. Whether or not compensation was necessary was based on the shape of the MNF-force relationship. A significant compensation of the MNF was found for the repetitive isokinetic contractions. In conclusion, when investigating maximum dynamic contractions, decreases in MNF can be due to mechanisms similar to those found during sustained static contractions (force-independent component of fatigue) and in some subjects due to a direct effect of the change in force (force-dependent component of fatigue). In order to compare MNF shifts during sustained static and repetitive dynamic contractions it is necessary to estimate the force-dependent component of fatigue of dynamic contractions. Our results are preliminary and have to be confirmed in larger experiments using single dynamic contractions when determining the MNF-force relationship of the unfatigued situation.
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| 32. |
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| 33. |
- Lim, Jang-Kwon, et al.
(författare)
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A theoretical and experimental comparison of 4H- and 6H-SiC MSM UV photodetectors
- 2012
-
Ingår i: Silicon Carbide and Related Materials 2011. - : Trans Tech Publications Inc.. - 9783037854198 ; , s. 1207-1210
-
Konferensbidrag (refereegranskat)abstract
- This paper reports on fabrication and modeling of 4H- and 6H-SiC metal-semiconductor-metal (MSM) photodetectors (PDs). MSM PDs have been fabricated on 4H-SiC and 6H-SiC epitaxial layers, and their performance analyzed by MEDICI simulation and measurements. The simulations were also used to optimize the sensitivity by varying the width and spacing of the interdigitated electrodes. The fabricated PDs with 2 ÎŒm wide metal electrodes and 3 ÎŒm spacing between the electrodes exhibited, under UV illumination, a peak current to dark current ratio of 10 5 and 10 4 in 4H-SiC and 6H-SiC, respectively. The measured spectral responsivity of 6H-SiC PDs was higher compared to that of 4H-SiC PDs, with a cutoff at 407 nm compared to 384 nm in 4H-SiC PDs. Also the peak responsivity occurred at a shorter wavelength in 6H material. A high rejection ratio between the photocurrent and dark current was found in both cases. These experimental results were in agreement with simulation.
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| 34. |
- Magnusson, Mikael S., et al.
(författare)
-
Experimental Evaluation of the Interfibre Joint Strength of Papermaking Fibres in Terms of Manufacturing Parameters and in Two Different Loading Directions
- 2013
-
Ingår i: Experimental mechanics. - : Springer Science and Business Media LLC. - 0014-4851 .- 1741-2765. ; 53:9, s. 1621-1634
-
Tidskriftsartikel (refereegranskat)abstract
- The strength properties of interfibre bonds play a vital role in the response of fibrous materials, such as paper and paperboard, under mechanical loading. To help tailor the properties of such materials by chemical or mechanical treatments of the fibre wall and fibre surfaces, improved understanding of the microscopic damage and failure mechanisms of interfibre joints is desirable. In this paper, a method for manufacturing and testing of interfibre joint specimens in two principally different modes of loading is presented. The method was applied to investigate the strength of Kraft pulp interfibre joints with different geometries and in two different modes of loading: the conventional shearing mode and also a peeling mode of loading. The method was also used to investigate the influence of drying pressure, defined as the nominal pressure between two Teflon surfaces or between a rubber surface and a Teflon one as well as a simple comparison of a pulp with two different degrees of refining. The results are presented in terms of rupture force and using different methods of normalization such as nominal overlap area, length, and width of the joint region, measured using a microscope. It was shown in this study that normalising the force at rupture by either geometric parameter reduced the scatter of the strength measurements slightly, but, neither were unambiguously more successful than the other. The results of tests done with the peeling type of loading were about 20 % of those done with the conventional shearing type of loading.
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| 35. |
- Magnusson, Mikael S., et al.
(författare)
-
Experimental evaluation of the interfibre joint strength ofpapermaking fibres in terms of manufacturing parameters and intwo different loading directions
- 2012
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The strength properties of interfibre bonds play a vital role in the response of fibrous materials,such as paper and paperboard, under mechanical loading. To help tailor the properties of suchmaterials by chemical or mechanical treatments of the fibre wall and fibre surfaces, improvedunderstanding of the microscopic damage and failure mechanisms of interfibre joints is desirable.In this paper, a method for manufacturing and testing of interfibre joint specimens in twoprincipally different modes of loading is presented.The method was applied to investigate the strength of Kraft pulp interfibre joints with differentgeometries and in two different modes of loading: the conventional shearing mode and also apeeling mode of loading. The method was also used to investigate the influence of dryingpressure, defined as the nominal pressure between two Teflon surfaces or between a rubbersurface and a Teflon one as well as a simple comparison of a pulp with two different degrees ofrefining.The results are presented in terms of rupture force and using different methods of normalizationsuch as nominal overlap area, length, and width of the joint region, measured using a microscope.It was shown in this study that neither of the methods of normalization unambiguously reducedthe large scatter of the strength measurements. The results of tests done with the peeling type ofloading were about 20 % of those done with the conventional shearing type of loading.
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| 36. |
- Magnusson, Mikael S.
(författare)
-
Interfibre Joint Strength under Mixed Modes of Loading
- 2014
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The load carrying capacity of interbre joints are one of the key entities for build-up of strength inpaper materials. In order to gain insight in how to tailor the macroscopic properties of such materialsby chemical and/or mechanical treatments at a microscopic level, direct measurement of individualbre{bre crosses are typically performed. However, the state of loading in the interbre joint, intesting of individual bre{bre crosses, is in general very complex and an increased understandingfor how to evaluate the mechanical properties of interbre joints is desirable. In Paper A, amethod for manufacturing and measuring the strength of isolated interbre joints is presented. Themethod is applied to investigate the strength of bre{bre crosses at two dierent modes of loading.Also, an investigation on the manufacturing conditions is presented. The strength distribution ofindividually prepared bre{bre crosses is characterized and it was found that the median strengthin a peeling type of loading was about 20% compared to samples tested in the conventional shearingtype of loading. In Paper B, a procedure for evaluating interbre joint strength measurementsin terms of resultant forces and moments in the interbre joint region is presented. The methodis applied to investigate the state of loading in bre{bre crosses tested in peeling and shearing,respectively. It is shown that for a typical interbre joint strength test, the load components otherthan shear, cannot in general be neglected and is strongly dependent on the structural geometry ofthe bre{bre crosses. In Paper C, four distinctly dierent load cases; peeling, shearing, tearingand a biaxial type of loading was tested mechanically and evaluated numerically in order to gainmore information on how interbre joints behave in dierent modes of loading. In Paper D, thein uence of a chemical additive on the interbre joint strength is investigated on the microscopic(joint) scale and correlated to the eect previously observed on the macroscopic (sheet) scale. Xraymicrotomography and image analysis was used to understand structural changes in the brousnetwork in terms of the number of interbre joints as well as the average interbre joint contact area.The results showed that the median interbre joint strength increased by 18% upon adsorption, andthat the polyelectrolyte increased the number of contacts between the bres as well as an increasedarea of contact. In Paper E, the damage behaviour of individual interbre joints is analyzed. Froman extensive number of mechanical tests, the typical damage behaviour is identied and a failurecriterion is used to study the in uence of failure properties to give indications on how to tailor thematerial to optimize the joint strength.
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| 37. |
- Magnusson, Mikael S., 1984-, et al.
(författare)
-
Interfibre joint strength under peeling, shearing and tearing types of loading
- 2013
-
Ingår i: Advances in Pulp and Paper Research, Cambridge 2013. - 9780992616304 ; , s. 103-124
-
Konferensbidrag (refereegranskat)abstract
- The mechanical properties of interfibre joints are essential for the load carrying capacity of fibre network materials such as paper and board. Mechanical measurements of fibre–fibre crosses can been used to characterize the strength of these interfibre joints in order to obtain knowledge on how these hierarchical network materials behave at the micrometer scale. The general method for these interfibre joint strength experiments has been to pull one of the fibres of a fibre–fibre cross and attribute the force at rupture to the shear strength of the interfibre joint. However, without taking the geometry of the fibres and the resulting mixed mode of loading at the interfibre joints into account, limited information on the strength properties can be obtained using this technique. In this study, isolated fibre–fibre crosses have been tested mechanically using four distinctly different load cases; peeling, shearing, tearing and a biaxial type of loading, in order to gain more information on how interfibre joints behave in different modes of loading. The centerline geometry of the fibres, microfibril angles, initial twists as well as the wall thickness of each individual test piece was used to model each experiment using the finite element method, and from the simulation results, the local state of loading in the interfibre joints at failure was obtained for each specific experiment. The force–displacement curve for the experiments as well as the estimated local state of loading was also used to compare the different load cases and to evaluate the information that can be obtained on the strength properties of interfibre joints using these load cases.
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| 38. |
- Magnusson, Mikael S., et al.
(författare)
-
Numerical evaluation of interfibre joint strength measurements in terms of three-dimensional resultant forces and moments
- 2013
-
Ingår i: Cellulose. - : Springer Science and Business Media LLC. - 0969-0239 .- 1572-882X. ; 20:4, s. 1691-1710
-
Tidskriftsartikel (refereegranskat)abstract
- The interfibre joint is one of the key elements in creating the strength of self-binding fibrous materials such as paper and board. In order evaluate the strength properties of interfibre joints using direct measurements, a greater understanding on how the mode of loading influences the results is desirable. The methods reported in the literature do not in general distinguish between the contributions of normal and shear stresses in the bonded region. This paper presents a numerical analysis procedure, based on the finite element method, for evaluating interfibre joint strength measurements in terms of the normal, shear, and moment loading components during testing. The target is to estimate the resultant forces and moments, that acts in the interfibre joint region at rupture, of Kraft pulp interfibre joints tested under two principally different modes of loading. The results show that for a typical interfibre joint test, modes of loading other than pure shear cannot, in general, be neglected, and are strongly dependent on the structural geometry of the fibre-fibre crosses. In addition, the resultant forces and moments were scaled in terms of the interface area and the twisting and bending resistance of the interface approximated as an ellipse to account for differences in interface area between the measurements. These scaled resultants were used to quantify how the mode of loading influences the relation between the amount of normal stress and the amount of shear stress that develop in the interfibre joint.
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| 39. |
- Magnusson, Mikael S., et al.
(författare)
-
Numerical evaluation of interfibre joint strength measurements in terms of three–dimensional resultant forces and moments
- 2012
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The interfibre joint is one of the key elements in creating the strength of self–binding fibrous materials such as paper and board. In order to tailor the properties of such materials by chemical and/or mechanical treatments of the fibres, and to learn how such modifications influence the properties at the microscopic level, a greater understanding of how to evaluate the mechanical properties of interfibre joints is desirable. The methods reported in the literature for determining of the interfibre joint strength do not in general distinguish between the contributions of normal and shear stresses in the bonded region. This paper presents a numerical analysis procedure, based on the finite element method, for evaluating interfibre joint strength measurements in terms of the normal, shear, and moment loading components during testing. The method is applied to investigate the strength of Kraft pulp interfibre joints under two principally different modes of loading. The results show that for a typical interfibre joint test of an isolated fibre–fibre cross with long free fibre segments, modes of loading other than pure shear cannot, in general, be neglected, and are strongly dependent on the structural geometry of the fibre–fibre crosses. In addition, the resultant forces and moments were scaled in terms of the interface area and the twisting and bending resistance of the interface approximated as an ellipse to account for differences in interface area between the measurements. These scaled resultants were used to quantify how the mode of loading influences the relation between the amount of normal stress and the amount of shear stress that develop in the interfibre joint.
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| 40. |
- Magnusson, Mikael S., 1984-
(författare)
-
Testing and Evaluation of Interfibre Joint Strength under Mixed-Mode Loading
- 2013
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The failure properties of interfibre bonds are the key for the build-up of strength in fibrous materials such as paper and paperboard. In order to tailor the properties of such materials by chemical or mechanical treatments and to learn how such modifications influence the properties at a microscopic level, direct measurement of individual fibre--fibre crosses are typically performed. However, the state of loading in the interfibre joint, in testing of individual fibre--fibre crosses, is in general very complex and a greater understanding for how to evaluate the mechanical properties of interfibre joints is desirable.In Paper A, a method for manufacturing multiple fibre--fibre cross specimens and a procedure for testing interfibre joints at different modes of loading is presented. The method is applied to investigate the strength of fibre-fibre crosses with different geometry and at two principally different modes of loading. Also, an investigation on the influence of drying pressure, the drying method as well as a comparison of pulp fibres from two different degrees of refining is presented. The force at rupture is scaled in terms of different geometric parameters; nominal overlap area, length and width of the joint region. It is shown that neither of the methods of scaling unambiguously reduced the coefficient of variation of the mean strength and that the force at rupture in a peeling type of loading was about 20% of the ones tested in the conventional shearing type of loading.In Paper B, a procedure for evaluating interfibre joint strength measurements in terms of resultant forces and moments at rupture is presented. The method is applied to investigate the state of loading in fibre-fibre crosses tested in two principally different modes of loading. It is shown that for a typical interfibre joint test, the modes of loading other than pure shear, cannot in general be neglected and is strongly dependent on the structural geometry of the fibre-fibre crosses. Also, the stress state in the interface centroid was estimated in order to quantify how the mode of loading influence the amount of normal stresses that develop in relation to the amount of shear stresses in the interfibre joint.
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| 41. |
- Mellin, Pelle, et al.
(författare)
-
A proposed Swedish national standard and best practice for detection of Ar in PM hip material
- 2018
-
Ingår i: Euro PM 2018 Congress and Exhibition. - : European Powder Metallurgy Association (EPMA). - 9781899072507
-
Konferensbidrag (refereegranskat)abstract
- Ar in metal is present as gaseous voids which affect the material performance; most notably the mechanical properties. In agreement with literature findings, our investigation confirms this for 316L steel produced by PM HIP. Detecting the Ar is possible by microscopy, but more reliably with inert gas fusion followed by gas chromatography or mass spectrometry. The users of these techniques have accumulated experience over the years and consider them robust, especially in terms of distinguishing a presence or absence of Ar. Since consensus has emerged, a standard is now possible. We propose firstly a national standard. It may be used as a quality agreement between the purchaser and provider of the PM HIP service. The proposed standard considers the distinctiveness of PM HIP. For example that Ar tends to segregate in PM HIP cans. In fact, consensus has also been reached on how to reliably sample from PM HIP cans. © European Powder Metallurgy Association (EPMA).
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| 42. |
- Naredi, S., et al.
(författare)
-
An outcome study of severe traumatic head injury using the "Lund therapy" with low-dose prostacyclin
- 2001
-
Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley-Blackwell. - 0001-5172 .- 1399-6576. ; 45:4, s. 402-406
-
Tidskriftsartikel (refereegranskat)abstract
- Background: There are two independent head injury outcome studies using the “Lund concept”, and both showed a mortality rate of about 10%, and a favourable outcome (Glasgow outcome scale, GOS 4 and 5) of about 70%. The Lund concept aims at controlling intracranial pressure, and improving microcirculation around contusions. Intracranial pressure is controlled by maintaining a normal colloid osmotic pressure and reducing the hydrostatic capillary pressure. Microcirculation is improved by ensuring strict normovolaemia and reducing sympathetic discharge. The endogenous substance prostacyclin with its antiaggregatory/antiadhesive effects may further improve microcirculation, which finds support from a microdialysis‐based clinical study and an experimental brain trauma study. The present clinical outcome study aims at evaluating whether the previously obtained good outcome with the Lund therapy can be reproduced, and whether the addition of prostacyclin has any adverse side‐effects.Methods: All 31 consecutive patients with severe head injury, Glasgow coma scale (GCS) ≤8, admitted to the University Hospital of Umeå during 1998 were included. The Lund therapy including prostacyclin infusion for the first three days at a dose of 0.5 ng kg−1 min−1. Outcome was evaluated according to the GOS >10 months after the injury.Results: One patient died, another suffered vegetative state and 7 severe disability. Of the 22 patients with favourable outcome, 19 showed good recovery and 3 moderate disability. No adverse side‐effects of prostacyclin were observed.Conclusion: The outcome results from previous studies using the Lund therapy were reproduced, and no adverse side‐effects of low‐dose prostacyclin were observed.
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| 43. |
- Prakash, Varsha, et al.
(författare)
-
Ribosome biogenesis during cell cycle arrest fuels EMT in development and disease
- 2019
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Ribosome biogenesis is a canonical hallmark of cell growth and proliferation. Here we show that execution of Epithelial-to-Mesenchymal Transition (EMT), a migratory cellular program associated with development and tumor metastasis, is fueled by upregulation of ribosome biogenesis during G1/S arrest. This unexpected EMT feature is independent of species and initiating signal, and is accompanied by release of the repressive nucleolar chromatin remodeling complex (NoRC) from rDNA, together with recruitment of the EMT-driving transcription factor Snai1 (Snail1), RNA Polymerase I (Pol I) and the Upstream Binding Factor (UBF). EMT-associated ribosome biogenesis is also coincident with increased nucleolar recruitment of Rictor, an essential component of the EMT-promoting mammalian target of rapamycin complex 2 (mTORC2). Inhibition of rRNA synthesis in vivo differentiates primary tumors to a benign, Estrogen Receptor-alpha (ER alpha) positive, Rictor-negative phenotype and reduces metastasis. These findings implicate the EMT-associated ribosome biogenesis program with cellular plasticity, de-differentiation, cancer progression and metastatic disease.
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| 44. |
- Quin, Jaclyn E., et al.
(författare)
-
Major transcriptional changes observed in the Fulani, an ethnic group less susceptible to malaria
- 2017
-
Ingår i: eLIFE. - 2050-084X. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- The Fulani ethnic group has relatively better protection from Plasmodium falciparum malaria, as reflected by fewer symptomatic cases of malaria, lower infection rates, and lower parasite densities compared to sympatric ethnic groups. However, the basis for this lower susceptibility to malaria by the Fulani is unknown. The incidence of classic malaria resistance genes are lower in the Fulani than in other sympatric ethnic populations, and targeted SNP analyses of other candidate genes involved in the immune response to malaria have not been able to account for the observed difference in the Fulani susceptibility to P.falciparum. Therefore, we have performed a pilot study to examine global transcription and DNA methylation patterns in specific immune cell populations in the Fulani to elucidate the mechanisms that confer the lower susceptibility to P.falciparum malaria. When we compared uninfected and infected Fulani individuals, in contrast to uninfected and infected individuals from the sympatric ethnic group Mossi, we observed a key difference: a strong transcriptional response was only detected in the monocyte fraction of the Fulani, where over 1000 genes were significantly differentially expressed upon P.falciparum infection.
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| 45. |
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| 46. |
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| 47. |
- Wallentin, Lars, et al.
(författare)
-
Lipoprotein-Associated Phospholipase A(2) Activity Is a Marker of Risk But Not a Useful Target for Treatment in Patients With Stable Coronary Heart Disease
- 2016
-
Ingår i: Journal of the American Heart Association. - 2047-9980. ; 5:6
-
Tidskriftsartikel (refereegranskat)abstract
- Background - We evaluated lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) activity in patients with stable coronary heart disease before and during treatment with darapladib, a selective Lp-PLA(2) inhibitor, in relation to outcomes and the effects of darapladib in the STABILITY trial.Methods and Results - Plasma Lp-PLA(2) activity was determined at baseline (n=14 500); at 1 month (n=13 709); serially (n=100) at 3, 6, and 18 months; and at the end of treatment. Adjusted Cox regression models evaluated associations between Lp-PLA(2) activity levels and outcomes. At baseline, the median Lp-PLA(2) level was 172.4 mu mol/min per liter (interquartile range 143.1-204.2 mu mol/min per liter). Comparing the highest and lowest Lp-PLA(2) quartile groups, the hazard ratios were 1.50 (95% CI 1.23-1.82) for the primary composite end point (cardiovascular death, myocardial infarction, or stroke), 1.95 (95% CI 1.29-2.93) for hospitalization for heart failure, 1.42 (1.07-1.89) for cardiovascular death, and 1.37 (1.03-1.81) for myocardial infarction after adjustment for baseline characteristics, standard laboratory variables, and other prognostic biomarkers. Treatment with darapladib led to a approximate to 65% persistent reduction in median Lp-PLA(2) activity. There were no associations between on-treatment Lp-PLA(2) activity or changes of Lp-PLA(2) activity and outcomes, and there were no significant interactions between baseline and on-treatment Lp-PLA(2) activity or changes in Lp-PLA(2) activity levels and the effects of darapladib on outcomes.Conclusions - Although high Lp-PLA(2) activity was associated with increased risk of cardiovascular events, pharmacological lowering of Lp-PLA(2) activity by approximate to 65% did not significantly reduce cardiovascular events in patients with stable coronary heart disease, regardless of the baseline level or the magnitude of change of Lp-PLA(2) activity.
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| 48. |
- Östlund, G., et al.
(författare)
-
Vitality among Swedish post-polio patients : A physiological phenomenon
- 2008
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Ingår i: Journal of Rehabilitation Medicine. - 1650-1977. ; 40, s. 709-714
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate quality of life, especially vitality and fatigue, in patients with postpolio syndrome (PPS), and the relative contributions of physiological and psychological parameters for level of vitality. Design: Multi-center study. Subjects: 143 patients, diagnosed with PPS from four Swedish post-polio out-clinics. Methods: Inventories of background information, quality of life (SF36), fatigue (MFI20) and sleep quality (SQS) were used. Pain was evaluated by a VAS scale. Descriptive statistics were used for examinations of demographic data, pain, quality of life, fatigue and sleep. Correlations included all selected parameters. Hierarchical regression models were constructed to examine predictors of variations in vitality, pain, reduced activity and physical fatigue. Results: General fatigue accounted for 68% of the variation in vitality. Of this, 91% was in turn accounted for by physiological indicators. After control for age, the physiological block of variables accounted for 56.6% and 25% of the variation in vitality, if entered before and after the psychological block of variables, respectively, while the impact of the psychological block almost disappeared after accounting for the physiological indicators. Physical fatigue, age and sleep quality were associated with variation in pain, whereas BMI, pain and sleep quality accounted for differences in reduced activity and physical fatigue. Conclusions: The phenomenon of vitality in PPS patients is mostly dependent on physiological parameters and mental fatigue is not a prominent predictor of vitality in PPS. The existence of subgroups of PPS patients with and without fatigue, independent of age or polio duration, needs further study.
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| 49. |
- Östlund, N., et al.
(författare)
-
Multichannel filter for heartbeat detection in noisy ECG recordings
- 2006
-
Ingår i: WORLD CONGRESS ON MEDICAL PHYSICS AND BIOMEDICAL ENGINEERING 2006, VOL 14, PTS 1-6.
-
Konferensbidrag (refereegranskat)abstract
- In ECG signals recorded with smart clothes disturbances as intermittent loss of signal from electrodes, movement artefacts, and electromyographic interference are common. In this study a multichannel method for spatio-temporal filtering is evaluated using ECG signals from a database and with three recordings made with a T-shirt with integrated textile electrodes. The sensitivity and precision of the signals from the database were 99.6% and 98.5%, respectively, if 12 channels were used and the signal-to-noise ratio was -10 dB. The filter gave a sensitivity of 99.6% and a precision of 99.5% in the recordings from the textile electrodes. In conclusion, the results obtained indicated that multichannel spatio-temporal filtration could be a suitable method for heartbeat detection in ECG measurements with textile electrodes.
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| 50. |
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