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2.
  • Bergström, Göran, 1964, et al. (författare)
  • Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
  • 2021
  • Ingår i: Circulation. - Philadelphia : American Heart Association. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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3.
  • Bergström, Göran, et al. (författare)
  • Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
  • 2021
  • Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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4.
  • Cederström, Sofia, et al. (författare)
  • Association between high-sensitivity C-reactive protein and coronary atherosclerosis in a general middle-aged population.
  • 2023
  • Ingår i: Scientific reports. - : Springer Nature. - 2045-2322. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite abundant knowledge about the relationship between inflammation and coronary atherosclerosis, it is still unknown whether systemic inflammation measured as high-sensitivity C-reactive protein (hsCRP) is associated with coronary atherosclerosis in a general population. This study aimed to examine the association between hsCRP and coronary computed tomography angiography (CCTA)-detected coronary atherosclerosis in a population-based cohort. Out of 30,154 randomly invited men and women aged 50 to 64years in the Swedish Cardiopulmonary Bioimage Study (SCAPIS), 25,408 had a technically acceptable CCTA and analysed hsCRP. Coronary atherosclerosis was defined as presence of plaque of any degree in any of 18 coronary segments. HsCRP values were categorised in four groups. Compared with hsCRP below the detection limit, elevated hsCRP (≥2.3mg/L) was weakly associated with any coronary atherosclerosis (OR 1.15, 95% CI 1.07-1.24), coronary diameter stenosis≥50% (OR 1.27, 95% CI 1.09-1.47),≥4 segments involved (OR 1.13, 95% CI 1.01-1.26 ) and severe atherosclerosis (OR 1.33, 95% CI 1.05-1.69) after adjustment for age, sex and traditional risk factors. The associations were attenuated after further adjustment for body mass index (BMI), although elevated hsCRP still associated with noncalcified plaques (OR 1.16, 95% CI 1.02-1.32), proposed to be more vulnerable. In conclusion, the additional value of hsCRP to traditional risk factors in detection of coronary atherosclerosis is low. The association to high-risk noncalcified plaques, although unlikely through a causal pathway, could explain the relationship between hsCRP and clinical coronary events in numerous studies.
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5.
  • Einarsdottir, Berglind Osk, 1979, et al. (författare)
  • A patient-derived xenograft pre-clinical trial reveals treatment responses and a resistance mechanism to karonudib in metastatic melanoma
  • 2018
  • Ingår i: Cell Death & Disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 9:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Karonudib (TH1579) is a novel compound that exerts anti-tumor activities and has recently entered phase I clinical testing. The aim of this study was to conduct a pre-clinical trial in patient-derived xenografts to identify the possible biomarkers of response or resistance that could guide inclusion of patients suffering from metastatic melanoma in phase II clinical trials. Patient-derived xenografts from 31 melanoma patients with metastatic disease were treated with karonudib or a vehicle for 18 days. Treatment responses were followed by measuring tumor sizes, and the models were categorized in the response groups. Tumors were harvested and processed for RNA sequencing and protein analysis. To investigate the effect of karonudib on T-cell-mediated anti-tumor activities, tumor-infiltrating T cells were injected in mice carrying autologous tumors and the mice treated with karonudib. We show that karonudib has heterogeneous anti-tumor effect on metastatic melanoma. Thus, based on the treatment responses, we could divide the 31 patient-derived xenografts in three treatment groups: progression group (32%), suppression group (42%), and regression group (26%). Furthermore, we show that karonudib has anti-tumor effect, irrespective of major melanoma driver mutations. Also, we identify high expression of ABCB1, which codes for p-gp pumps as a resistance biomarker. Finally, we show that karonudib treatment does not hamper T-cell-mediated anti-tumor responses. These findings can be used to guide future use of karonudib in clinical use with a potential approach as precision medicine.
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6.
  • Engström, Gunnar, et al. (författare)
  • Pulmonary function and atherosclerosis in the general population : causal associations and clinical implications
  • 2024
  • Ingår i: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 39:1, s. 35-49
  • Tidskriftsartikel (refereegranskat)abstract
    • Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50–64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.
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  • Ericson, Oskar, et al. (författare)
  • The Potential Cost and Cost-Effectiveness Impact of Using a Machine Learning Algorithm for Early Detection of Sepsis in Intensive Care Units in Sweden
  • 2022
  • Ingår i: Journal of health economics and outcomes research. - : The Journal of Health Economics and Outcomes Research. - 2326-697X .- 2327-2236. ; 9:1, s. 101-110
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Early diagnosis of sepsis has been shown to reduce treatment delays, increase appropriate care, and reduce mortality. The sepsis machine learning algorithm NAVOY® Sepsis, based on variables routinely collected at intensive care units (ICUs), has shown excellent predictive properties. However, the economic consequences of forecasting the onset of sepsis are unknown.Objectives: The potential cost and cost-effectiveness impact of a machine learning algorithm forecasting the onset of sepsis was estimated in an ICU setting.Methods: A health economic model has been developed to capture short-term and long-term consequences of sepsis. The model is based on findings from a randomized, prospective clinical evaluation of NAVOY® Sepsis and from literature sources. Modeling the relationship between time from sepsis onset to treatment and prevalence of septic shock and in-hospital mortality were of particular interest. The model base case assumes that the time to treatment coincides with the time to detection and that the algorithm predicts sepsis 3 hours prior to onset. Total costs include the costs of the prediction algorithm, days spent at the ICU and hospital ward, and long-term consequences. Costs are estimated for an average patient admitted to the ICU and for the healthcare system. The reference method is sepsis diagnosis in accordance with clinical practice.Results: In Sweden, the total cost per patient amounts to €16 436 and €16 512 for the algorithm and current practice arms, respectively, implying a potential cost saving per patient of €76. The largest cost saving is for the ICU stay, which is reduced by 0.16 days per patient (5860 ICU days for the healthcare sector) resulting in a cost saving of €1009 per ICU patient. Stochastic scenario analysis showed that NAVOY® Sepsis was a dominant treatment option in most scenarios and well below an established threshold of €20 000 per quality-adjusted life-year. A 3-hour faster detection implies a reduction in in-hospital mortality, resulting in 356 lives saved per year.Conclusions: A sepsis prediction algorithm such as NAVOY® Sepsis reduces the cost per ICU patient and will potentially have a substantial cost-saving and life-saving impact for ICU departments and the healthcare system.
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  • Kronschläger, Martin, et al. (författare)
  • Protective Effect of The Thioltransferase Gene On In Vivo UVR-300 nm Induced Cataract : In vivo protection of Grx1 against UVR in the lens
  • 2012
  • Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 53:1, s. 248-252
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose. To determine the protection factor (PF) for glutaredoxin-1 (Grx1) with regard to UVR-induced cataract by comparison of in vivo ultraviolet radiation (UVR) lens toxicity between double knockout Grx1−/− and Grx1+/+ mice.Methods. Twenty Grx1+/+ mice and 20 Grx1−/− mice were unilaterally exposed in vivo to UVR for 15 minutes. Groups of four animals each received 0.0, 2.1, 2.9, 3.6, and 4.1 kJ/m2 UVR-300 nm. At 48 hours after UVR exposure, light-scattering in the exposed and contralateral nonexposed lenses was measured quantitatively. Macroscopic lens changes were documented with dark-field illumination photography.Results. UVR-300 nm induced subcapsular and cortical cataract in Grx1−/− and Grx1+/+ mice. In both Grx1−/− and Grx1+/+, the light-scattering intensified with increased in vivo exposure doses of UVR-300 nm. The intensity of forward light-scattering was higher in the lenses of Grx1−/− mice than in the lenses of Grx1+/+ mice. The threshold dose for in vivo UVR-300 nm–induced cataract, expressed as MTD2.3:16, was 3.8 in the Grx1+/+ group and 3.0 in the Grx1−/− group, resulting in a PF of 1.3.Conclusions. The PF is an objective relative measure of protective properties. The Grx1 gene is associated with an in vivo PF of 1.3. This result signifies that the presence of the gene allows a 1.3 times longer in vivo exposure to UVR, at equivalent irradiance, than the absence of the gene before early-onset, UVR-induced cataract occurs. This finding indicates the important role of the Grx1 gene in the oxidation defense system of the lens.
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10.
  • Kvarnström, Maria, 1971-, et al. (författare)
  • Myelin protein P0-specific IgM producing monoclonal B cell lines were established from polyneuropathy patients with monoclonal gammopathy of undetermined significance (MGUS)
  • 2002
  • Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 127:2, s. 255-262
  • Tidskriftsartikel (refereegranskat)abstract
    • Monoclonal expansion of B cells and plasma cells, producing antibodies against ‘self’ molecules, can be found not only in different autoimmune diseases, such as peripheral neuropathy (PN), but also in malignancies, such as Waldenström’s macroglobulinaemia and B-type of chronic lymphocytic leukaemia (B-CLL), as well as in precancerous conditions including monoclonal gammopathy of undetermined significance (MGUS). About 50% of patients with PN-MGUS have serum antibodies against peripheral nerve myelin, but the specific role of these antibodies remains uncertain. The aims of the study were to establish, and characterize, myelin-specific B cell clones from peripheral blood of patients with PN-MGUS, by selection of cells bearing specific membrane Ig-receptors for myelin protein P0, using beads coated with P0. P0-coated magnetic beads were used for selection of cells, which subsequently were transformed by Epstein–Barr virus. The specificity of secreted antibodies was tested by ELISA. Two of the clones producing anti-P0 antibodies were selected and expanded. The magnetic selection procedure was repeated and new clones established. The cells were CD5+ positive, although the expression declined in vitro over time. The anti-P0 antibodies were of IgM-λ type. The antibodies belonged to the VH3 gene family with presence of somatic mutations. The IgM reacted with P0 and myelin-associated glycoprotein (MAG), and showed no evidence for polyreactivity, in contrast to other IgM CD5+ clones included in the study as controls. The expanded clones expressed CD80 and HLA-DR, which is compatible with properties of antigen-presenting cells. The immunomagnetic selection technique was successfully used for isolation of antimyelin protein P0-specific clones. The cell lines may provide useful tools in studies of monoclonal gammopathies, leukaemia, and autoimmune diseases, including aspects of antigen-presentation by these cells followed by T cell activation.
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11.
  • Larsson, Erik, et al. (författare)
  • INTERNET OF THINGS AS A COMPLEMENT TO INCREASE SAFETY
  • 2020
  • Ingår i: Journal of the Belarusian State University. International Relations. - 2521-6848. ; 2020:1, s. 88-93
  • Tidskriftsartikel (refereegranskat)abstract
    • Safety evaluations made in the city Helsingborg indicate a decreased risk of being exposed to crime, but an increased feeling of unsafe. Damage in the form of scribbling (graffiti) is one of several indicators contributing to feeling unsafe. In this paper we investigate whether the use of Internet­-of-­things technology, where a sensor monitors a walking and cycling tunnel, makes it possible to reduce scribbling. The study shows a number of interesting results. When the sensor was in­ stalled, the public showed a great and positive interest. A short time after installation, the sensor was subjected to a qua­lified attack where heavy shocks were followed by an initiated way to determine if the sensor was damaged. A setting and tuning phase was used to empirically test different settings of the sensor to detect scribbling behavior. However, it became evident during the approximately 6­month long measurement period that we received many false alarms, which were, for example, that people took shelter in the tunnel in the rain and stood or walked slowly when using their mobile phone. Du­ ring the measurement period, two scribbles occurred where the sensor detected one of them. We observe that the amount of scribbling has decreased significantly. The number of error reports on scribbling dropped from an average of 3.33 per month before the sensor was in place to 0.75 cases per month after the sensor was in place.
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12.
  • Lundqvist, Joakim, et al. (författare)
  • The AAA(+) motor complex of subunits CobS and CobT of cobaltochelatase visualized by single particle electron microscopy
  • 2009
  • Ingår i: Journal of Structural Biology. - : Elsevier BV. - 1047-8477 .- 1095-8657. ; 167:3, s. 227-234
  • Tidskriftsartikel (refereegranskat)abstract
    • Cobalamins belong to the tetrapyrrole family of prosthetic groups. The presence of a metal ion is a key feature of these compounds. In the oxygen-dependent (aerobic) cobalamin biosynthetic pathway, cobalt is inserted into a ring-contracted tetrapyrrole called hydrogenobyrinic acid a,c-diamide (HBAD) by a cobaltochelatase that is constituted by three subunits, CobN, CobS and COT, with molecular masses of 137, 37 and 71 kDa, respectively. Based on the similarities with magnesium chelatase, cobaltochelatase has been suggested to belong to the AAA(+) superfamily of proteins. In this paper we present the cloning of the Brucella melitensis cobN, cobS and cobT, the purification of the encoded protein products, and a single-particle reconstruction of the macromolecular assembly formed between CobS and COT from negatively stained electron microscopy images of the complex. The results show for the first time that subunits CobS and COT form a chaperone-like complex, characteristic for the AAA(+) class of proteins. The molecules are arranged in a two-tiered ring structure with the six subunits in each ring organized as a trimer of dimers. The similarity between this structure and that of magnesium chelatase, as well as analysis of the amino acid sequences confirms the suggested evolutionary relationship between the two enzymes.
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14.
  • Löf, Liza, et al. (författare)
  • Flow Cytometric Measurement of Blood Cells with BCR-ABL1 Fusion Protein in Chronic Myeloid Leukemia
  • 2017
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic myeloid leukemia (CML) is characterized in the majority of cases by a t(9;22)(q34;q11) translocation, also called the Philadelphia chromosome, giving rise to the BCR-ABL1 fusion protein. Current treatment with tyrosine kinase inhibitors is directed against the constitutively active ABL1 domain of the fusion protein, and minimal residual disease (MRD) after therapy is monitored by real-time quantitative PCR (RQ-PCR) of the fusion transcript. Here, we describe a novel approach to detect and enumerate cells positive for the BCR-ABL1 fusion protein by combining the in situ proximity ligation assay with flow cytometry as readout (PLA-flow). By targeting of the BCR and ABL1 parts of the fusion protein with one antibody each, and creating strong fluorescent signals through rolling circle amplification, PLA-flow allowed sensitive detection of cells positive for the BCR-ABL1 fusion at frequencies as low as one in 10,000. Importantly, the flow cytometric results correlated strongly to those of RQ-PCR, both in diagnostic testing and for MRD measurements over time. In summary, we believe this flow cytometry-based method can serve as an attractive approach for routine measurement of cells harboring BCR-ABL1 fusions, also allowing simultaneously assessment of other cell surface markers as well as sensitive longitudinal follow-up.
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16.
  • Nilsson, Jonas, et al. (författare)
  • Tests of HPGe- and scintillation-based backpack γ-radiation survey systems.
  • 2014
  • Ingår i: Journal of Environmental Radioactivity. - : Elsevier BV. - 1879-1700 .- 0265-931X. ; 135:Apr 24, s. 54-62
  • Tidskriftsartikel (refereegranskat)abstract
    • The performance of three different backpack-mounted γ-radiation survey systems has been investigated. The systems are based on a LaBr3:Ce detector and a NaI(Tl) detector both with active volume dimensions of 76.2 mm in diameter and 76.2 mm length and a 123% relative efficiency HPGe detector. The detection limits of the systems were tested in a controlled outdoor environment in Sweden, followed by field tests of the HPGe- and LaBr3:Ce-based systems at the site of a radioactive waste repository in Georgia (in the Caucasus region of Eurasia). The results showed that the high efficiency HPGe detector performed significantly better than similar sized LaBr3:Ce and NaI(Tl) detectors, however, the HPGe detector was significantly heavier than the other systems. The use of different analysis methods revealed that creating maps of the survey area was the best method for offline analysis of survey data collected from a large area. Using off-site personnel for analysis of the data proved to be beneficial.
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17.
  • Nordström, Eva, et al. (författare)
  • ABBV-0805, a novel antibody selective for soluble aggregated alpha-synuclein, prolongs lifespan and prevents buildup of alpha-synuclein pathology in mouse models of Parkinson's disease
  • 2021
  • Ingår i: Neurobiology of Disease. - : Elsevier. - 0969-9961 .- 1095-953X. ; 161
  • Tidskriftsartikel (refereegranskat)abstract
    • A growing body of evidence suggests that aggregated alpha-synuclein, the major constituent of Lewy bodies, plays a key role in the pathogenesis of Parkinson's disease and related alpha-synucleinopathies. Immunotherapies, both active and passive, against alpha-synuclein have been developed and are promising novel treatment strategies for such disorders. Here, we report on the humanization and pharmacological characteristics of ABBV-0805, a monoclonal antibody that exhibits a high selectivity for human aggregated alpha-synuclein and very low affinity for monomers. ABBV-0805 binds to a broad spectrum of soluble aggregated alpha-synuclein, including small and large aggregates of different conformations. Binding of ABBV-0805 to pathological alpha-synuclein was demonstrated in Lewy body-positive post mortem brains of Parkinson's disease patients. The functional potency of ABBV-0805 was demonstrated in several cellular assays, including Fc gamma-receptor mediated uptake of soluble aggregated alpha-synuclein in microglia and inhibition of neurotoxicity in primary neurons. In vivo, the murine version of ABBV-0805 (mAb47) displayed significant dose dependent decrease of alpha-synuclein aggregates in brain in several mouse models, both in prophylactic and therapeutic settings. In addition, mAb47 treatment of alpha-synuclein transgenic mice resulted in a significantly prolonged survival. ABBV-0805 selectively targets soluble toxic alpha-synuclein aggregates with a picomolar affinity and demonstrates excellent in vivo efficacy. Based on the strong preclinical findings described herein, ABBV-0805 has been progressed into clinical development as a potential disease-modifying treatment for Parkinson's disease.
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19.
  • Persson, Inger, et al. (författare)
  • A Machine Learning Sepsis Prediction Algorithm for Intended Intensive Care Unit Use (NAVOY Sepsis) : Proof-of-Concept Study
  • 2021
  • Ingår i: JMIR Formative Research. - : JMIR Publications. - 2561-326X. ; 5:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background:  Despite decades of research, sepsis remains a leading cause of mortality and morbidity in intensive care units worldwide. The key to effective management and patient outcome is early detection, for which no prospectively validated machine learning prediction algorithm is currently available for clinical use in Europe.Objective:  We aimed to develop a high-performance machine learning sepsis prediction algorithm based on routinely collected intensive care unit data, designed to be implemented in European intensive care units.Methods:  The machine learning algorithm was developed using convolutional neural networks, based on Massachusetts Institute of Technology Lab for Computational Physiology MIMIC-III clinical data from intensive care unit patients aged 18 years or older. The model uses 20 variables to produce hourly predictions of onset of sepsis, defined by international Sepsis-3 criteria. Predictive performance was externally validated using hold-out test data.Results:  The algorithm-NAVOY Sepsis-uses 4 hours of input and can identify patients with high risk of developing sepsis, with high performance (area under the receiver operating characteristics curve 0.90; area under the precision-recall curve 0.62) for predictions up to 3 hours before sepsis onset.Conclusions:  The prediction performance of NAVOY Sepsis was superior to that of existing sepsis early warning scoring systems and comparable with those of other prediction algorithms designed to predict sepsis onset. The algorithm has excellent predictive properties and uses variables that are routinely collected in intensive care units.
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21.
  • Söderberg, Håkan, 1966, et al. (författare)
  • In video war games, are military personnel's fixation patterns different compared with those of civilians?
  • 2012
  • Ingår i: The Journal of Defense Modeling and Simulation: Applications, Methodology, Technology. - : Sage Publications. - 1557-380X .- 1548-5129. ; 11:4, s. 329-338
  • Tidskriftsartikel (refereegranskat)abstract
    • For combat personnel in urban operations, situational awareness is critical and of major importance for a safe and efficient performance. One way to train situational awareness is to adopt video games. Twenty military and 20 civilian subjects played the game “Close Combat: First to Fight” on two different platforms, Xbox and PC, wearing an eye tracker. The purpose was to investigate if the visual search strategies used in a game correspond to live training, and how military-trained personnel search for visual information in a game environment. A total of 27,081 fixations were generated through a centroid mode algorithm and analyzed frame-by-frame, 48% of them from military personnel. Military personnel’s visual search strategies were different from those of civilians. Fixation durations were, however, equally short, that is, about 170 ms, for both groups. Surprisingly, the military-trained personnel’s fixation patterns were less orientated towards tactical objects and areas of interest than the civilians’; the underlying mechanisms remaining unclear. Military training was apparently not advantageous with respect to playing “Close Combat: First to Fight”. Further research within the area of gaming, military training and visual search strategies is warranted.
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23.
  • Welén Schef, Kerstin, et al. (författare)
  • Prevalence of angina pectoris and association with coronary atherosclerosis in a general population
  • 2023
  • Ingår i: Heart. - : BMJ Publishing Group Ltd. - 1355-6037 .- 1468-201X. ; 109:19, s. 1450-1459
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To assess the contemporary prevalence of, and factors associated with angina pectoris symptoms, and to examine the relationship to coronary atherosclerosis in a middle-aged, general population.Methods: Data were based on the Swedish CArdioPulmonary bioImage Study (SCAPIS), in which 30 154 individuals were randomly recruited from the general population between 2013 and 2018. Participants that completed the Rose Angina Questionnaire were included and categorised as angina or no angina. Subjects with a valid coronary CT angiography (CCTA) were categorised by degree of coronary atherosclerosis; ≥50% obstruction (obstructive coronary atherosclerosis), <50% obstruction or any atheromatosis (non-obstructive coronary atherosclerosis) or none (no coronary atherosclerosis).Results: The study population consisted of 28 974 questionnaire responders (median age 57.4 years, female 51.6%, hypertension 19.9%, hyperlipidaemia 7.9%, diabetes mellitus 3.7%), of which 1025 (3.5%) fulfilled the criteria of angina. Coronary atherosclerosis was more common in individuals having angina compared with those with no angina (n=24 602, obstructive coronary atherosclerosis 11.8% vs 5.4%, non-obstructive coronary atherosclerosis 38.9% vs 37.0%, no coronary atherosclerosis 49.4% vs 57.7%, all p<0.001). Factors independently associated with angina were birthplace outside of Sweden (OR 2.58 (95% CI 2.10 to 2.92)), low educational level (OR 1.41 (1.10 to 1.79)), unemployment (OR 1.51 (1.27 to 1.81)), poor economic status (OR 1.85 (1.38 to 2.47)), symptoms of depression (OR 1.63 (1.38 to 1.92)) and high degree of stress (OR 2.92 (1.80 to 4.73)).Conclusion: Angina pectoris symptoms are common (3.5%) among middle-aged individuals of the general population of Sweden, though with low association to obstructive coronary atherosclerosis. Sociodemographic and psychological factors are highly associated with angina symptoms, irrespective of degree of coronary atherosclerosis.
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25.
  • Wijk, Helle, 1958, et al. (författare)
  • Verksamhetsförlagd utbildning på avancerad nivå : ny utmaning för specialistutbildningar för sjuksköterskor
  • 2009
  • Ingår i: Vård i Norden. - København : Sjuksköterskornas samarbete i Norden. - 0107-4083 .- 1890-4238. ; 29:94, s. 41-43
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • The aim of this article is to discuss challenges in the development of Specialist Nursing Educations as a result of the 2007 Swedish Higher EducationReform: the implementation of the so-called Bologna process. Certain challenges follow this reform, particularly since the specialist nursingprogrammes will be part of the second cycle of the higher education system, and it will be possible to combine the professional degree witha masters degree (one year). Possible strategies in four areas related to the Specialist Nursing Education are discussed: integration of researchbasedknowledge, experienced-based knowledge, improvement knowledge, and strategies for collaboration between university institutions andclinics. Specific didactical issues are raised.
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26.
  • Zarnegar, Behdad, et al. (författare)
  • Influenza Infection in Mice Induces Accumulation of Lung Mast Cells through the Recruitment and Maturation of Mast Cell Progenitors
  • 2017
  • Ingår i: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Mast cells (MCs) are powerful immune cells that mature in the peripheral tissues from bone marrow (BM)-derived mast cell progenitors (MCp). Accumulation of MCs in lung compartments where they are normally absent is thought to enhance symptoms in asthma. The enrichment of lung MCs is also observed in mice subjected to models of allergic airway inflammation. However, whether other types of lung inflammation trigger increased number of MCp, which give rise to MCs, is unknown. Here, mouse-adapted H1N1 influenza A was used as a model of respiratory virus infection. Intranasal administration of the virus induced expression of VCAM-1 on the lung vascular endothelium and an extensive increase in integrin beta 7(hi) lung MCp. Experiments were performed to distinguish whether the influenza-induced increase in the number of lung MCp was triggered mainly by recruitment or in situ cell proliferation. A similar proportion of lung MCp from influenza-infected and PBS control mice were found to be in a proliferative state. Furthermore, BM chimeric mice were used in which the possibility of influenza-induced in situ cell proliferation of host MCp was prevented. Influenza infection in the chimeric mice induced a similar number of lung MCp as in normal mice. These experiments demonstrated that recruitment of MCp to the lung is the major mechanism behind the influenza-induced increase in lung MCp. Fifteen days post-infection, the influenza infection had elicited an immature MC population expressing intermediate levels of integrin beta 7, which was absent in controls. At the same time point, an increased number of toluidine blue(+) MCs was detected in the upper central airways. When the inflammation was resolved, the MCs that accumulated in the lung upon influenza infection were gradually lost. In summary, our study reveals that influenza infection induces a transient accumulation of lung MCs through the recruitment and maturation of MCp. We speculate that temporary augmented numbers of lung MCs are a cause behind virus-induced exacerbations of MC-related lung diseases such as asthma.
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27.
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28.
  • Öhlén, Joakim, 1958, et al. (författare)
  • A Clinical Intervention Model for Communication and Information Focusing on Existential Uncertainty – A Participatory Action Research Project Informed by Qualitative Outcome Analysis
  • 2011
  • Ingår i: Supportive Care in Cancer. ; 19:Suppl 2
  • Konferensbidrag (refereegranskat)abstract
    • Objectives. The aim was to develop a team oriented intervention model for palliative cancer care focusing on communicating changes in goals of care. Methods. A participatory action research project was designed by means of qualitative outcome analysis. Initially, bimonthly focus groups with one palliative care team at an oncology outpatient unit were performed during one and a half year. Previous major results, from qualitative studies into patients’ knowledge seeking and experiences of communication and information in palliative cancer care, were used as facilitators for discussion and reflection on the team’s professional experiences. Collaboratively, the researchers and the team worked on developing an intervention model for communication and information. Group discussion data were analyzed concurrently. A preliminary clinical intervention model was developed and refined by means of focus groups with additional palliative care teams and patients respectively. Results. A model of communication and information in palliative cancer care aimed for clinical intervention will be presented, including main concepts, strategies and outcomes. The focus of the model is communication of changes in patients’ goals of care in relation to progress of disease as well as patients’ existential uncertainty (conceptualized as certainty–uncertainty). Conclusions. The model is found to have clinical fit, thanks of the collaborative development by clinicians and researchers. The next step is to further evaluate it clinically.
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29.
  • Öhlén, Joakim, 1958, et al. (författare)
  • Students’ learning as the focus for shared involvement between universities and clinical practice : a didactic model for postgraduate degree projects
  • 2012
  • Ingår i: Advances in Health Sciences Education. - Dordrecht : Springer Netherlands. - 1382-4996 .- 1573-1677. ; 17:4, s. 471-487
  • Tidskriftsartikel (refereegranskat)abstract
    • In an academic programme, completion of a postgraduate degree project could be a significant means of promoting student learning in evidence- and experience-based practice. In specialist nursing education, which through the European Bologna process would be raised to the master’s level, there is no tradition of including a postgraduate degree project. The aim was to develop a didactic model for specialist nursing students’ postgraduate degree projects within the second cycle of higher education (master’s level) and with a specific focus on nurturing shared involvement between universities and healthcare settings. This study embodies a participatory action research and theory-generating design founded on empirically practical try-outs. The 3-year project included five Swedish universities and related healthcare settings. A series of activities was performed and a number of data sources secured. Constant comparative analysis was applied. A didactic model is proposed for postgraduate degree projects in specialist nursing education aimed at nurturing shared involvement between universities and healthcare settings. The focus of the model is student learning in order to prepare the students for participation as specialist nurses in clinical knowledge development. The model is developed for the specialist nursing education, but it is general and could be applicable to various education programmes. © 2011 Springer Science+Business Media B.V.
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