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2.
  • Astvaldsdottir, A., et al. (författare)
  • Oral health and dental care of older persons-A systematic map of systematic reviews
  • 2018
  • Ingår i: Gerodontology. - : Wiley. - 0734-0664 .- 1741-2358. ; 35:4, s. 290-304
  • 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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  • Fernández-Ardèvol, M., et al. (författare)
  • Methodological Strategies to Understand Smartphone Practices for Social Connectedness in Later Life
  • 2019
  • 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
  • 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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4.
  • Hagström, Emil, et al. (författare)
  • Growth Differentiation Factor 15 Predicts All-Cause Morbidity and Mortality in Stable Coronary Heart Disease
  • 2017
  • Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 63:1, s. 325-333
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Higher growth differentiation factor 15 (GDF-15) concentrations are associated with cardiovascular (CV) and non-CV morbidity and mortality. However, information on associations between GDF-15 and the risk of specific CV and non-CV events in stable coronary heart disease (CHD) patients is limited.METHODS: In 14 577 patients with stable CHD participating in the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial (STABILITY), GDF-15 and other prognostic biomarkers (N-terminal pro-B-type natriuretic peptide, high-sensitivity troponin T, cystatin C, and high-sensitivity C-reactive protein) were measured. In adjusted Cox regression models, the associations between GDF-15 and the composite CV end point [CV death, myocardial infarction (MI), and stroke], as well as other CV and non-CV events, were assessed.RESULTS: The median concentration (interquartile range) of GDF-15 at baseline was 1253 (915-1827) ng/L. The hazard ratio for the composite end point for the highest compared to the lowest quartile of GDF-15 was 1.8 (95% CI, 1.5-2.2); for CV death, 2.63 (1.9-3.6); for sudden death, 3.06 (1.9-4.8); for heart failure (HF) death, 4.3 (1.3-14); for cancer death, 2.5 (1.3-4.7); for hospitalization for HF, 5.8 (3.2-10); for MI 1.4 (95% CI, 1.1-1.9); and for stroke, 1.8 (95% CI, 1.1-2.8). After adjustment for other prognostic biomarkers, GDF-15 remained significantly associated with all outcomes except for MI.CONCLUSIONS: In stable CHD, GDF-15 was independently associated with CV, non-CV, and cancer mortality, as well as with MI and stroke. When also adjusting for other prognostic biomarkers, the associations to all fatal and nonfatal events were maintained except for MI. Information on GDF-15, therefore, might be helpful when assessing the risk of adverse outcomes in patients with stable CHD. ClinicalTrials.gov Identifier: NCT00799903.
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5.
  • Hultcrantz, Monica, et al. (författare)
  • The GRADE Working Group clarifies the construct of certainty of evidence
  • 2017
  • Ingår i: Journal of Clinical Epidemiology. - : Pergamon Press. - 0895-4356 .- 1878-5921. ; 87, s. 4-13
  • 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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6.
  • Lim, Jang-Kwon, et al. (författare)
  • 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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7.
  • Vedin, Ola, et al. (författare)
  • Associations between tooth loss and prognostic biomarkers and the risk for cardiovascular events in patients with stable coronary heart disease
  • 2017
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 245, s. 271-276
  • Tidskriftsartikel (refereegranskat)abstract
    • Background:Underlying mechanisms behind the hypothesized relationship between periodontal disease (PD) and coronary heart disease (CHD) have been insufficiently explored. We evaluated associations between self-reported tooth loss-a marker of PD- and prognostic biomarkers in 15,456 (97%) patients with stable CHD in the global STABILITY trial.Methods and results:Baseline blood samples were obtained and patients reported their number of teeth according to the following tooth loss levels: "26-32 (All)" [lowest level], "20-25", "15-19", "1-14", and "No Teeth" [highest level]. Linear and Cox regression models assessed associations between tooth loss levels and biomarker levels, and the relationship between tooth loss levels and outcomes, respectively.After multivariable adjustment, the relative biomarker increase between the highest and the lowest tooth loss level was: high-sensitivity C-reactive protein 1.21 (95% confidence interval, 1.14-1.29), interleukin 6 1.14 (1.10-1.18), lipoprotein-associated phospholipase A(2) activity 1.05 (1.03-1.06), growth differentiation factor 15 1.11 (1.08-1.14), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) 1.18 (1.11-1.25). No association was detected for high-sensitivity troponin T 1.02 (0.98-1.05). Some attenuation of the relationship between tooth loss and outcomes resulted from the addition of biomarkers to the multivariable analysis, of which NT-proBNP had the biggest impact.Conclusions:A graded and independent association between tooth loss and several prognostic biomarkers was observed, suggesting that tooth loss and its underlying mechanisms may be involved in multiple pathophysiological pathways also implicated in the development and prognosis of CHD. The association between tooth loss and cardiovascular death and stroke persisted despite comprehensive adjustment including prognostic biomarkers.
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  • 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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  • Almuzzaini, Bader, et al. (författare)
  • In beta-actin knockouts, epigenetic reprogramming and rDNA transcription inactivation lead to growth and proliferation defects
  • 2016
  • Ingår i: The FASEB Journal. - 0892-6638 .- 1530-6860. ; 30:8, s. 2860-2873
  • 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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  • Almuzzaini, Bader, et al. (författare)
  • Nuclear myosin 1 contributes to a chromatin landscape compatible with RNA polymerase II transcription activation
  • 2015
  • Ingår i: BMC Biology. - : Springer Science and Business Media LLC. - 1741-7007. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Nuclear myosin 1c (NM1) is emerging as a regulator of transcription and chromatin organization. Results: Using chromatin immunoprecipitation and deep sequencing (ChIP-Seq) in combination with molecular analyses, we investigated the global association of NM1 with the mammalian genome. Analysis of the ChIP-Seq data demonstrates that NM1 binds across the entire mammalian genome with occupancy peaks correlating with distributions of RNA Polymerase II (Pol II) and active epigenetic marks at class II gene promoters. In mouse embryonic fibroblasts subjected to RNAi mediated NM1 gene silencing, we show that NM1 synergizes with polymerase-associated actin to maintain active Pol II at the promoter. NM1 also co-localizes with the nucleosome remodeler SNF2h at class II promoters where they assemble together with WSTF as part of the B-WICH complex. A high resolution micrococcal nuclease (MNase) assay and quantitative real time PCR shows that this mechanism is required for local chromatin remodeling. Following B-WICH assembly, NM1 mediates physical recruitment of the histone acetyl transferase PCAF and the histone methyl transferase Set1/Ash2 to maintain and preserve H3K9acetylation and H3K4trimethylation for active transcription. Conclusions: We propose a novel genome-wide mechanism where myosin synergizes with Pol II-associated actin to link the polymerase machinery with permissive chromatin for transcription activation.
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  • Böhm, Felix, et al. (författare)
  • FFR-Guided Complete or Culprit-Only PCI in Patients with Myocardial Infarction
  • 2024
  • Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 390:16, s. 1481-1492
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The benefit of fractional flow reserve (FFR)-guided complete revascularization in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease remains unclear. METHODS: In this multinational, registry-based, randomized trial, we assigned patients with STEMI or very-high-risk non-STEMI (NSTEMI) and multivessel disease who were undergoing primary percutaneous coronary intervention (PCI) of the culprit lesion to receive either FFR-guided complete revascularization of nonculprit lesions or no further revascularization. The primary outcome was a composite of death from any cause, myocardial infarction, or unplanned revascularization. The two key secondary outcomes were a composite of death from any cause or myocardial infarction and unplanned revascularization. RESULTS: A total of 1542 patients underwent randomization, with 764 assigned to receive FFR-guided complete revascularization and 778 assigned to receive culprit-lesion-only PCI. At a median follow-up of 4.8 years (interquartile range, 4.3 to 5.2), a primary-outcome event had occurred in 145 patients (19.0%) in the complete-revascularization group and in 159 patients (20.4%) in the culprit-lesion-only group (hazard ratio, 0.93; 95% confidence interval [CI], 0.74 to 1.17; P = 0.53). With respect to the secondary outcomes, no apparent between-group differences were observed in the composite of death from any cause or myocardial infarction (hazard ratio, 1.12; 95% CI, 0.87 to 1.44) or unplanned revascularization (hazard ratio, 0.76; 95% CI, 0.56 to 1.04). There were no apparent between-group differences in safety outcomes. CONCLUSIONS: Among patients with STEMI or very-high-risk NSTEMI and multivessel coronary artery disease, FFR-guided complete revascularization was not shown to result in a lower risk of a composite of death from any cause, myocardial infarction, or unplanned revascularization than culprit-lesion-only PCI at 4.8 years. (Funded by the Swedish Research Council and others; FULL REVASC ClinicalTrials.gov number, NCT02862119.).
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  • Calado Botelho, Salomé, et al. (författare)
  • The association of Brahma with the Balbiani ring 1 gene of Chironomus tentans studied by immunoelectron microscopy and chromatin immunoprecipitation
  • 2008
  • Ingår i: Insect molecular biology (Print). - : Wiley. - 0962-1075 .- 1365-2583. ; 17:5, s. 505-13
  • Tidskriftsartikel (refereegranskat)abstract
    • Many steps of gene expression take place during transcription, and important functional information can thus be obtained by determining the distribution of specific factors along a transcribed gene. The Balbiani ring (BR) genes of the dipteran Chironomus tentans constitute a unique system for mapping the association of specific factors along a eukaryotic gene using immuno-electron microscopy (immuno-EM). The chromatin immunoprecipitation (ChIP) technique has provided an alternative, more general method for studying the association of proteins with specific genomic sequences. The immuno-EM and the ChIP methods suffer from different limitations, and thus a combination of both is advantageous. We have established optimal conditions for ChIP on chromatin extracted from the salivary glands of C. tentans, and we have analyzed the association of the SWI/SNF chromatin remodelling factor Brahma (Brm) with the BR1 gene by combined immuno-EM and ChIP. We show that Brm is not restricted to the promoter of the BR1 gene but is also associated with sequences in the middle and distal portions of the gene, which suggests that Brm has additional roles apart from regulating transcription initiation.
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17.
  • Dominic, Chris A. S., et al. (författare)
  • Towards a conceptual sustainable packaging development model : A corrugated box case study
  • 2015
  • Ingår i: Packaging technology & science. - New York : Wiley. - 0894-3214 .- 1099-1522. ; 28:5, s. 397-413
  • 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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  • Fadl, Helena E., 1965-, et al. (författare)
  • Maternal and neonatal outcomes and time trends of gestational diabetes mellitus in Sweden from 1991 to2003
  • 2010
  • Ingår i: Diabetic Medicine. - Malden 02148, MA USA : Wiley-Blackwell. - 0742-3071 .- 1464-5491. ; 27:4, s. 436-441
  • 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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  • Fadl, Helena, 1965-, et al. (författare)
  • Gestational diabetes mellitus and later cardiovascular disease : a Swedish population based case-control study
  • 2014
  • Ingår i: British Journal of Obstetrics and Gynecology. - : Wiley-Blackwell. - 1470-0328 .- 1471-0528. ; 121:12, s. 1530-1536
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To identify if gestational diabetes mellitus (GDM) is a clinically useful marker of future cardiovascular disease (CVD) risk and if GDM combined with other risks (smoking, hypertension or body mass) identifies high-risk groups.Design: Population-based matched case-control study.Setting: National Swedish register data from 1991 to 2008.Population: A total of 2639 women with a cardiovascular event and matched controls.Methods: Conditional logistic regression examined associations with CVD before and after adjustment for conventional risk factors and confounders. Effect modification for the association of GDM with CVD by body mass index (BMI), smoking and chronic hypertension was assessed by stratification and interaction testing. Adjustment for diabetes post-pregnancy evaluated its mediating role.Main outcome measures: Inpatient diagnoses or causes of death identifying ischemic heart disease, ischemic stroke, atherosclerosis or peripheral vascular disease.Results: The adjusted odds ratios (and 95% confidence intervals) for the association of CVD with GDM are 1.51 (1.07-2.14), 2.23 (2.01-2.48) for smoking, 1.98 (1.71-2.29) for obesity and 5.10 (3.18-8.18) for chronic hypertension. In stratified analysis the association of CVD with GDM was only seen among women with BMI 25, with an odds ratio of 2.39 (1.39-4.10), but only women with a BMI <30 accounted for this increased risk. Adjustment for post-pregnancy diabetes attenuated it somewhat to 1.99 (1.13-3.52).Conclusions: In the absence of other recognised cardiovascular risk factors, such as smoking, obesity or chronic hypertension, GDM is a useful marker of raised CVD risk among women with BMI between 25 and 29.
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20.
  • Held, Claes, 1956-, et al. (författare)
  • 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
  • Ingår i: Journal of the American Heart Association. - 2047-9980. ; 6:10
  • 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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22.
  • Hofmann, Robin, et al. (författare)
  • Oxygen therapy in suspected acute myocardial infarction
  • 2017
  • Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 377:13, s. 1240-1249
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The clinical effect of routine oxygen therapy in patients with suspected acute myocardial infarction who do not have hypoxemia at baseline is uncertain. METHODS: In this registry-based randomized clinical trial, we used nationwide Swedish registries for patient enrollment and data collection. Patients with suspected myocardial infarction and an oxygen saturation of 90% or higher were randomly assigned to receive either supplemental oxygen (6 liters per minute for 6 to 12 hours, delivered through an open face mask) or ambient air. RESULTS: A total of 6629 patients were enrolled. The median duration of oxygen therapy was 11.6 hours, and the median oxygen saturation at the end of the treatment period was 99% among patients assigned to oxygen and 97% among patients assigned to ambient air. Hypoxemia developed in 62 patients (1.9%) in the oxygen group, as compared with 254 patients (7.7%) in the ambient-air group. The median of the highest troponin level during hospitalization was 946.5 ng per liter in the oxygen group and 983.0 ng per liter in the ambient-air group. The primary end point of death from any cause within 1 year after randomization occurred in 5.0% of patients (166 of 3311) assigned to oxygen and in 5.1% of patients (168 of 3318) assigned to ambient air (hazard ratio, 0.97; 95% confidence interval [CI], 0.79 to 1.21; P=0.80). Rehospitalization with myocardial infarction within 1 year occurred in 126 patients (3.8%) assigned to oxygen and in 111 patients (3.3%) assigned to ambient air (hazard ratio, 1.13; 95% CI, 0.88 to 1.46; P=0.33). The results were consistent across all predefined subgroups. CONCLUSIONS: Routine use of supplemental oxygen in patients with suspected myocardial infarction who did not have hypoxemia was not found to reduce 1-year all-cause mortality. (Funded by the Swedish Heart–Lung Foundation and others; DETO2X-AMI ClinicalTrials.gov number, NCT01787110.)
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23.
  • Hu, Yifei, et al. (författare)
  • Design and optimization procedure of a single-sided linear induction motor applied to an Articulated funiculator
  • 2016
  • Ingår i: 2016 IEEE 8th International Power Electronics and Motion Control Conference, IPEMC-ECCE Asia 2016. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781509012107 ; , s. 3096-3102
  • Konferensbidrag (refereegranskat)abstract
    • The paper describes the design of a single-sided linear induction motor (SLIM) intended for an Articulated Funiculator (AF). A procedure is proposed where first an analytical design is carried out to obtain a preliminary geometry. The analytical design is based on approximate equivalent circuits under constrained conditions. In the second step a two-dimensional finite element method (2D-FEM) analysis is performed to validate the accuracy of the analytical models. The modification and optimization are conducted to acquire the best design.
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24.
  • Jamialahmadi, A., et al. (författare)
  • Dynamic performance of corrugated boxes
  • 2008
  • Ingår i: Proceedings of the 16th IAPRI World Conference on Packaging. - : IAPRI.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • This paper summarizes dynamic analysis of the interaction of corrugated boxes in transport using a pressure-mapping system. The dynamic contact forces on the contact area between boxes in both vertical and horizontal directions were measured and the position of the instantaneous Centre of Force (COF) was traced from which the pitch motion of boxes relative to each other was studied. The level-crossing diagrams of the contact forces show a Rayleigh distribution for the vertical contact and a Gaussian distribution for horizontal contacts. The contact force and acceleration power spectral density from accelerometers and pressure-mapping system were compared.The results show that a pressure mapping system is an interesting tool for analysis of the dynamic performance of systems of corrugated boxes under different stacking and loading conditions.
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25.
  • Landen, Jaren W., et al. (författare)
  • Ponezumab in mild-to-moderate Alzheimer's disease : Randomized phase II PET-PIB study
  • 2017
  • Ingår i: Alzheimer's and Dementia: Translational Research and Clinical Interventions. - : Wiley. - 2352-8737. ; 3:3, s. 393-401
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction The safety, pharmacokinetics, and effect on peripheral and central amyloid β (Aβ) of multiple doses of ponezumab, an anti-Aβ monoclonal antibody, were characterized in subjects with mild-to-moderate Alzheimer's disease treated for 1 year. Methods Subjects were aged ≥50 years with Mini–Mental State Examination scores 16 to 26. Cohort Q was randomized to ponezumab 10 mg/kg (n = 12) or placebo (n = 6) quarterly. Cohort M was randomized to a loading dose of ponezumab 10 mg/kg or placebo, followed by monthly ponezumab 7.5 mg/kg (n = 12) or placebo (n = 6), respectively. Results Ponezumab was generally well tolerated. Plasma concentrations increased dose dependently, but cerebrospinal fluid (CSF) penetration was low. Plasma Aβ increased dose dependently with ponezumab, but CSF biomarkers, brain amyloid burden, cognition, and function were not affected. Conclusions Both ponezumab dosing schedules were generally safe and well tolerated but did not alter CSF biomarkers, brain amyloid burden, or clinical outcomes.
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26.
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27.
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28.
  • Lindholm, Daniel, 1982-, et al. (författare)
  • Biomarker-Based Risk Model to Predict Cardiovascular Mortality in Patients With Stable Coronary Disease
  • 2017
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 70:7, s. 813-826
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Currently, there is no generally accepted model to predict outcomes in stable coronary heart disease (CHD).Objectives This study evaluated and compared the prognostic value of biomarkers and clinical variables to develop a biomarker-based prediction model in patients with stable CHD.Methods In a prospective, randomized trial cohort of 13,164 patients with stable CHD, we analyzed several candidate biomarkers and clinical variables and used multivariable Cox regression to develop a clinical prediction model based on the most important markers. The primary outcome was cardiovascular (CV) death, but model performance was also explored for other key outcomes. It was internally bootstrap validated, and externally validated in 1,547 patients in another study.Results During a median follow-up of 3.7 years, there were 591 cases of CV death. The 3 most important biomarkers were N-terminal pro–B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and low-density lipoprotein cholesterol, where NT-proBNP and hs-cTnT had greater prognostic value than any other biomarker or clinical variable. The final prediction model included age (A), biomarkers (B) (NT-proBNP, hs-cTnT, and low-density lipoprotein cholesterol), and clinical variables (C) (smoking, diabetes mellitus, and peripheral arterial disease). This “ABC-CHD” model had high discriminatory ability for CV death (c-index 0.81 in derivation cohort, 0.78 in validation cohort), with adequate calibration in both cohorts.Conclusions This model provided a robust tool for the prediction of CV death in patients with stable CHD. As it is based on a small number of readily available biomarkers and clinical factors, it can be widely employed to complement clinical assessment and guide management based on CV risk. (The Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial [STABILITY]; NCT00799903)
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29.
  • Linvill, Eric (författare)
  • 3-D Forming of Paper Materials
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Paper materials have a long history of use as a packaging material, although traditional paper-based packaging is limited in its shape, complexity, and design. In order to better understand the deformation and failure mechanisms during 3-D forming, two experimental studies of paper materials have been conducted. Furthermore, constitutive modeling combined with explicit finite element modeling have been validated against numerous experimental setups and utilized to develop further understanding of 3-D forming processes.Two experimental studies were necessary to further investigate and model the 3-D formability of paper materials. The combined effect of moisture and temperature on the uniaxial mechanical properties of paper was investigated, providing new insights into how moisture and temperature affect both the elastic and plastic properties of paper materials. Furthermore, the in-plane, biaxial yield and failure surfaces were experimentally investigated in both stress and strain space, which gave an operating window for 3-D forming processes as well as input parameters for the constitutive models.The constitutive modeling of paper materials and explicit finite element modeling were directed towards two 3-D forming processes: deep drawing and hydroforming. The constitutive models were calibrated and validated against simple (typically uniaxial) mechanical tests, and the explicit finite element models (which utilize the developed constitutive models) were validated against 3-D forming experiments. Hand-made papers with fibers partially oxidized to dialcohol cellulose, which has greater extensibility than typical paper materials, was furthermore characterized, modeled, and 3-D formed as a demonstration of the potential of modified paper fiber products for 3-D forming applications.
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30.
  • Linvill, Eric, et al. (författare)
  • Advanced three-dimensional paper structures : Mechanical characterization and forming of sheets made from modified cellulose fibers
  • 2017
  • Ingår i: Materials & design. - : Elsevier. - 0264-1275 .- 1873-4197. ; 128, s. 231-240
  • Tidskriftsartikel (refereegranskat)abstract
    • Cellulose partially converted to dialcohol cellulose has been identified as a potential breakthrough material for the production of bio-based, complex, double-curved surfaces due to its extensive strain-at-break characteristics (reaching as great as 80% in tensile loading). Tensile testing of handsheets made from modified cellulose fibers was conducted from 50 to 90% relative humidity (RH) and from 23 to 150 °C. Strain-at-break of the handsheets ranged from 35 to 80% over this humidity and temperature range, which is significantly greater than typical cellulose-based materials. The combined effect of moisture and temperature was further investigated by dynamic mechanical thermal analysis, which was utilized to determine the glass-transition temperature of the handsheets as a function of relative humidity. Based on the tensile test results and verified by the three-dimensional (3-D) forming and simulation, a forming limit diagram (strain-based failure surface which describes and illustrates the formability of the material) for the handsheets was generated. This forming limit illustrates significant extent to which this bio-based material can be 3-D formed into advanced structures. Furthermore, temperature was identified as the best, quickest, and most controllable method of improving extensibility of this material during 3-D forming.
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31.
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32.
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33.
  • López-López, ÁJ., et al. (författare)
  • A variable no-load voltage scheme for improving energy efficiency in DC-electrified mass transit systems
  • 2014
  • Ingår i: 2014 Joint Rail Conference, JRC 2014. - 9780791845356
  • Konferensbidrag (refereegranskat)abstract
    • Railway mass transit systems like subways play a fundamental role in the concept of sustainable cities. In these systems, the amount of passengers strongly fluctuates along the day. Hence, in order to provide a proper service without incurring disproportionate energy consumption, operation at different traffic densities is required. The majority of underground systems are DC-electrified. Standard DC voltages in railway systems are low for historical and safety reasons. In the rush hours, the large number of trains demanding power of the system may lead to overloaded substations and voltage dips. This problem is partially mitigated by means of substation-transformer tap regulation, which allows operators to increase the no-load voltage. High no-load voltage has a beneficial effect at all trafficdensity scenarios in terms of transmission losses. However, at the same time it effectively reduces the system's capacity to absorb regenerated energy, which may lead to inefficient energy consumption figures during off-peak hours. In this paper, the sensitivity of system energy consumption to no-load voltage has been analyzed. Several traffic-density scenarios in a case-study system are explored. As a result, a scheduled no-load voltage scheme is proposed for the operation of the system. This operation strategy improves energy efficiency without incurring a high investment cost. The only costs related to this proposed method are the costs of wear-andtear in tap-changers. In case there are devices such as energy storage systems installed in the system, there would be additional operation costs related to a simultaneous update of the voltage limits for their operation.
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34.
  • Medronho, B., et al. (författare)
  • Cyclodextrin-grafted cellulose: Physico-chemical characterization
  • 2013
  • Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617. ; 93:1, s. 324-330
  • Tidskriftsartikel (refereegranskat)abstract
    • Cyclodextrins (CDs) can form inclusion complexes with a wide variety of molecules making them very attractive in different areas, such as pharmaceutics, biochemistry, food chemistry and textile. In this communication we will report on the physico-chemical characterization of cellulose modified with CDs by means of infra-red spectroscopy (FTIR), cross polarization magic angle spinning solid state nuclear magnetic resonance (CP-MAS NMR), polarized optical microscopy (POM) and thermal gravimetric analysis (TGA). Both CP-MAS NMR and FTIR indicate that CDs are chemically attached to cellulose backbone through the formation of ester bonds. Furthermore, the CD-grafted cellulose was dissolved in a "superphosphoric" acid solution but, despite the increase of hydrophilicity due to the modification, POM revealed that grafted cellulose was less soluble when compared to the unmodified polymer. The formation of a complex CD-cellulose network is suggested.
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35.
  • 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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37.
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38.
  • Porsch, Christian, et al. (författare)
  • In Vitro Evaluation of Non-Protein Adsorbing Breast Cancer Theranostics Based on 19F-Polymer Containing Nanoparticles
  • 2013
  • Ingår i: Particle and Particle Systems Characterization. - : Wiley. - 0934-0866 .- 1521-4117. ; 30:4, s. 381-390
  • Tidskriftsartikel (refereegranskat)abstract
    • Eight fluorinated nanoparticles (NPs) are synthesized, loaded with doxorubicin (DOX), and evaluated as theranostic delivery platforms to breast cancer cells. The multifunctional NPs are formed by self-assembly of either linear or star-shaped amphiphilic block copolymers, with fluorinated segments incorporated in the hydrophilic corona of the carrier. The sizes of the NPs confirm that small circular NPs are formed. The release kinetics data of the particles reveals clear hydrophobic core dependence, with longer sustained release from particles with larger hydrophobic cores, suggesting that the DOX release from these carriers can be tailored. Viability assays and flow cytometry evaluation of the ratios of apoptosis/necrosis indicate that the materials are non-toxic to breast cancer cells before DOX loading; however, they are very efficient, similar to free DOX, at killing cancer cells after drug encapsulation. Both flow cytometry and confocal microscopy confirm the cellular uptake of NPs and DOX-NPs into breast cancer cells, and in vitro 19F-MRI measurement shows that the fluorinated NPs have strong imaging signals, qualifying them as a potential in vivo contrast agent for 19F-MRI.
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39.
  • 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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40.
  • 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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41.
  • Rubertsson, Sten, et al. (författare)
  • Mechanical chest compressions and simultanous defibrillationvs conventional cardiopulmonary resuscitationin out-of hospital cardiac arrest:the LINC randomized trial
  • 2014
  • Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association. - 0098-7484 .- 1538-3598. ; 311:1, s. 53-61
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE: A strategy using mechanical chest compressions might improve the poor outcome in out-of-hospital cardiac arrest, but such a strategy has not been tested in large clinical trials. OBJECTIVE: To determine whether administering mechanical chest compressions with defibrillation during ongoing compressions (mechanical CPR), compared with manual cardiopulmonary resuscitation (manual CPR), according to guidelines, would improve 4-hour survival. DESIGN, SETTING, AND PARTICIPANTS: Multicenter randomized clinical trial of 2589 patients with out-of-hospital cardiac arrest conducted between January 2008 and February 2013 in 4 Swedish, 1 British, and 1 Dutch ambulance services and their referring hospitals. Duration of follow-up was 6 months. INTERVENTIONS: Patients were randomized to receive either mechanical chest compressions (LUCAS Chest Compression System, Physio-Control/Jolife AB) combined with defibrillation during ongoing compressions (n = 1300) or to manual CPR according to guidelines (n = 1289). MAIN OUTCOMES AND MEASURES: Four-hour survival, with secondary end points of survival up to 6 months with good neurological outcome using the Cerebral Performance Category (CPC) score. A CPC score of 1 or 2 was classified as a good outcome. RESULTS: Four-hour survival was achieved in 307 patients (23.6%) with mechanical CPR and 305 (23.7%) with manual CPR (risk difference, -0.05%; 95% CI, -3.3% to 3.2%; P > .99). Survival with a CPC score of 1 or 2 occurred in 98 (7.5%) vs 82 (6.4%) (risk difference, 1.18%; 95% CI, -0.78% to 3.1%) at intensive care unit discharge, in 108 (8.3%) vs 100 (7.8%) (risk difference, 0.55%; 95% CI, -1.5% to 2.6%) at hospital discharge, in 105 (8.1%) vs 94 (7.3%) (risk difference, 0.78%; 95% CI, -1.3% to 2.8%) at 1 month, and in 110 (8.5%) vs 98 (7.6%) (risk difference, 0.86%; 95% CI, -1.2% to 3.0%) at 6 months with mechanical CPR and manual CPR, respectively. Among patients surviving at 6 months, 99% in the mechanical CPR group and 94% in the manual CPR group had CPC scores of 1 or 2. CONCLUSIONS AND RELEVANCE: Among adults with out-of-hospital cardiac arrest, there was no significant difference in 4-hour survival between patients treated with the mechanical CPR algorithm or those treated with guideline-adherent manual CPR. The vast majority of survivors in both groups had good neurological outcomes by 6 months. In clinical practice, mechanical CPR using the presented algorithm did not result in improved effectiveness compared with manual CPR. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00609778.
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42.
  • Rubertsson, Sten, et al. (författare)
  • Per-Protocol and Pre-Defined population analysis of the LINC study
  • 2015
  • Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 96, s. 92-99
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To perform two predefined sub-group analyses within the LINC study and evaluate if the results were supportive of the previous reported intention to treat (ITT) analysis.METHODS: Predefined subgroup analyses from the previously published LINC study were performed. The Per-Protocol population (PPP) included the randomized patients included in the ITT-population but excluding those with violated inclusion or exclusion criteria and those that did not get the actual treatment to which the patient was randomized. In the Pre-Defined population (PDP) analyses patients were also excluded if the dispatch time to ambulance arrival at the address exceeded 12min, there was a non-witnessed cardiac arrest, or if it was not possible to determine whether the arrest was witnessed or not, and those cases where LUCAS was not brought to the scene at the first instance.RESULTS: After exclusion from the 2589 patients within the ITT-population, the Per-Protocol analysis was performed in 2370 patients and the Pre-Defined analysis within 1133 patients. There was no significant difference in 4-h survival of patients between the mechanical-CPR group and the manual-CPR group in the Per-Protocol population; 279 of 1172 patients (23.8%) versus 281 of 1198 patients (23.5%) (risk difference -0.35%, 95% C.I. -3.1 to 3.8, p=0.85) or in the Pre-Defined population; 176 of 567 patients (31.0%) versus 192 of 566 patients (33.9%) (risk difference -2.88%, 95% C.I. -8.3 to 2.6, p=0.31). There was no difference in any of the second outcome variables analyzed in the Pre-Protocol or Pre-Defined populations.CONCLUSIONS: The results from these predefined sub-group analyses of the LINC study population did not show any difference in 4h survival or in secondary outcome variables between patients treated with mechanical-CPR or manual-CPR. This is consistent with the previously published ITT analysis.
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43.
  • Sabri, N, et al. (författare)
  • Evidence for a Posttranscription Role of a TFIIIC-like Protein in Chironomus tentans.
  • 2002
  • Ingår i: Molecular Biology of the Cell. - : American Society for Cell Biology (ASCB). - 1059-1524 .- 1939-4586. ; 13, s. 1765-1777
  • Tidskriftsartikel (refereegranskat)abstract
    • We have cloned and sequenced a cDNA that encodes for a nuclear protein of 238 kDa in the dipteran Chironomus tentans. This protein, that we call p2D10, is structurally similar to the α subunit of the general transcription factor TFIIIC. Using immunoelectron microscopy we have shown that a fraction of p2D10 is located at sites of transcription, which is consistent with a possible role of this protein in transcription initiation. We have also found that a large fraction of p2D10 is located in the nucleoplasm and in the nuclear pore complexes. Using gel filtration chromatography and coimmunoprecipitation methods, we have identified and characterized two p2D10-containing complexes that differ in molecular mass and composition. The heavy p2D10-containing complex contains at least one other component of the TFIIIC complex, TFIIIC-ε. Based on its molecular mass and composition, the heavy p2D10-containing complex may be the Pol III holoenzyme. The light p2D10-containing complex contains RNA together with at least two proteins that are thought to be involved in mRNA trafficking, RAE1 and hrp65. The observations reported here suggest that this new TFIIIC-α-like protein is involved in posttranscriptional steps of premRNA metabolism in Chironomus tentans.
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44.
  • Stenninger, Erik, et al. (författare)
  • Continuous Subcutaneous Glucose Monitoring System in diabetic mothers during labour and postnatal glucose adaptation of their infants
  • 2008
  • Ingår i: Diabetic Medicine. - Oxford : Blackwell. - 0742-3071 .- 1464-5491. ; 25:4, s. 450-454
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims  To assess a new technique for continuous monitoring of glucose concentration during labour in diabetic mothers. A second objective was to study maternal glucose levels in relation to postnatal glucose adaptation and the need for intravenous (IV) glucose treatment in the newborn infant.Methods  Fifteen pregnant women with insulin-treated diabetes mellitus participated in this prospective pilot study. To measure their glucose control during labour we used the Continuous Subcutaneous Glucose Monitoring System (CGMS; Medtronic, Minneapolis, MN, USA) to calculate the mean glucose concentration and the area under the curve (AUC) in the last 120 min before delivery. All infants of these women were transferred to the neonatal care unit for early oral feeding and blood glucose measurements up to 14 h after delivery. Infants received IV glucose if blood glucose values were repeatedly < 2.2 mmol/l.Results  All women coped well with the CGMS monitoring. AUC 0–120 min before delivery, mean glucose concentration 0–120 min before delivery and cord plasma insulin level were all significantly associated with the need for IV glucose in the newborn children.Conclusions  In this study we found an association between maternal glucose concentrations during labour and postnatal glucose adaptation and need for IV glucose treatment in the infants. Online monitoring of glucose levels during delivery might help us to achieve maternal normoglycaemia and further reduce the risk of postnatal hypoglycaemia in the offspring.
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47.
  • von Walden, Ferdinand, et al. (författare)
  • Mechanical loading induces the expression of a Pol I regulon at the onset of skeletal muscle hypertrophy
  • 2012
  • Ingår i: American Journal of Physiology - Cell Physiology. - : American Physiological Society. - 0363-6143 .- 1522-1563. ; 302:10, s. c1523-C1530
  • Tidskriftsartikel (refereegranskat)abstract
    • von Walden F, Casagrande V, Ostlund Farrants AK, Nader GA. Mechanical loading induces the expression of a Pol I regulon at the onset of skeletal muscle hypertrophy. Am J Physiol Cell Physiol 302: C1523-C1530, 2012. First published March 7, 2012; doi:10.1152/ajpcell.00460.2011.-The main goal of the present study was to investigate the regulation of ribosomal DNA (rDNA) gene transcription at the onset of skeletal muscle hypertrophy. Mice were subjected to functional overload of the plantaris by bilateral removal of the synergist muscles. Mechanical loading resulted in muscle hypertrophy with an increase in rRNA content. rDNA transcription, as determined by 45S pre-rRNA abundance, paralleled the increase in rRNA content and was consistent with the onset of the hypertrophic response. Increased transcription and protein expression of c-Myc and its downstream polymerase I (Pol I) regulon (POL1RB, TIF-1A, PAF53, TTF1, TAF1C) was also consistent with the increase in rRNA. Similarly, factors involved in rDNA transcription, such as the upstream binding factor and the Williams syndrome transcription factor, were induced by mechanical loading in a corresponding temporal fashion. Chromatin immunoprecipitation revealed that these factors, together with Pol I, were enriched at the rDNA promoter. This, in addition to an increase in histone H3 lysine 9 acetylation, demonstrates that mechanical loading regulates rRNA synthesis by inducing a gene expression program consisting of a Pol I regulon, together with accessory factors involved in transcription and chromatin remodeling at the rDNA promoter. Altogether, these data indicate that transcriptional and epigenetic mechanisms take place in the regulation of ribosome production at the onset of muscle hypertrophy.
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48.
  • Waller, K. Persson, et al. (författare)
  • Genotypic characterization of Staphylococcus chromogenes and Staphylococcus simulans from Swedish cases of bovine subclinical mastitis
  • 2023
  • Ingår i: Journal of Dairy Science. - : American Dairy Science Association. - 0022-0302 .- 1525-3198. ; 106:11, s. 7991-8004
  • Tidskriftsartikel (refereegranskat)abstract
    • Staphylococcus chromogenes and Staphylococcus simulans are commonly found in intramammary infections (IMI) associated with bovine subclinical mastitis, but little is known about genotypic variation and relatedness within species. This includes knowledge about genes encoding antimicrobial resistance (AMR) and potential virulence factors (pVF). The aim of this study was therefore to investigate these aspects by whole-genome sequencing of milk isolates from Swedish dairy cows with subclinical mastitis in an observational study. We also wanted to study if specific genotypes were associated with persistent IMI and the inflammatory response at udder quarter level. In total, 105 and 118 isolates of S. chromogenes and S. simulans, respectively, were included. Isolates were characterized using a 7-locus multilocus sequence typing (7-MLST), core genome analysis and in-silico analysis of AMR and pVF genes. Forty-seven sequence types (ST) and 7 core genome clusters of S. chromogenes were identified, and the most common ST were ST-6 and ST-109, both belonging to cluster VII. A 7-locus MLST scheme for S. simulans was not available, but 3 core genome clusters and 5 subclusters were described. Overall, substantial variation in ST and clusters among cows and herds were found in both species. Some ST of S. chromogenes were found in several herds, indicating spread between herds. Moreover, within-herd spread of the same genotype was observed for both species. Only a few AMR genes (blaZ, strpS194, vga(A)) were detected in a limited number of isolates, with the exception of blaZ coding for β-lactamase, which was identified in 22% of the isolates of S. chromogenes with ST-19, ST-102, and ST-103 more commonly carrying this gene compared with other STs. However, the blaZ gene was not identified in S. simulans. The average total number of pVF detected per isolate was similar in S. chromogenes (n = 30) and S. simulans (n = 33), but some variation in total numbers and presence of specific pVF or functional groups of pVF, was shown between ST/clusters within species. Differences in inflammatory response and potentially in persistent IMI at udder quarter level were found between S. chromogenes subtypes but not between S. simulans subtypes. In conclusion, the results from the present study generates new insight into the epidemiology of bovine S. chromogenes and S. simulans IMI, which can have implications for future prevention and antimicrobial treatment of infections related to these species.
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