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1.
  • Ericsson, Olle, et al. (författare)
  • Clinical validation of a novel automated cell-free DNA screening assay for trisomies 21, 13, and 18 in maternal plasma.
  • 2019
  • Ingår i: Prenatal diagnosis. - 1097-0223. ; 39:11, s. 1011-1015
  • Tidskriftsartikel (refereegranskat)abstract
    • To evaluate clinical performance of a new automated cell-free (cf)DNA assay in maternal plasma screening for trisomies 21, 18, and 13, and to determine fetal sex.Maternal plasma samples from 1200 singleton pregnancies were analyzed with a new non-sequencing cfDNA method, which is based on imaging and counting specific chromosome targets. Reference outcomes were determined by either cytogenetic testing, of amniotic fluid or chorionic villi, or clinical examination of neonates.The samples examined included 158 fetal aneuploidies. Sensitivity was 100% (112/112) for trisomy 21, 89% (32/36) for trisomy 18, and 100% (10/10) for trisomy 13. The respective specificities were 100%, 99.5%, and 99.9%. There were five first pass failures (0.4%), all in unaffected pregnancies. Sex classification was performed on 979 of the samples and 99.6% (975/979) provided a concordant result.The new automated cfDNA assay has high sensitivity and specificity for trisomies 21, 18, and 13 and accurate classification of fetal sex, while maintaining a low failure rate. The study demonstrated that cfDNA testing can be simplified and automated to reduce cost and thereby enabling wider population-based screening.
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2.
  • Gustafsson, Harald, et al. (författare)
  • Den dubbla blicken. En inledning
  • 2007
  • Ingår i: Den dubbla blicken. Historia i de nordiska samhällena. - : Sekel Bokförlag. - 9789185767007 ; , s. 7-26
  • Bokkapitel (övrigt vetenskapligt)
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3.
  • Nyberg, Lena, 1979, et al. (författare)
  • A single-step competitive binding assay for mapping of single DNA molecules
  • 2012
  • Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier. - 0006-291X .- 1090-2104. ; 417:1, s. 404-408
  • Tidskriftsartikel (refereegranskat)abstract
    • Optical mapping of genomic DNA is of relevance for a plethora of applications such as scaffolding for sequencing and detection of structural variations as well as identification cif pathogens like bacteria and viruses. For future clinical applications it is desirable to have a fast and robust mapping method based on as few steps as possible. We here demonstrate a single-step method to obtain a DNA barcode that is directly visualized using nanofluidic devices and fluorescence microscopy. Using a mixture of YOYO-1, a bright DNA dye, and netropsin, a natural antibiotic with very high AT specificity, we obtain a DNA map with a fluorescence intensity profile along the DNA that reflects the underlying sequence. The netropsin binds to AT-tetrads and blocks these binding sites from YOYO-1 binding which results in lower fluorescence intensity from AT-rich regions of the DNA. We thus obtain a DNA barcode that is dark in AT-rich regions and bright in GC-rich regions with kilobasepair resolution. We demonstrate the versatility of the method by obtaining a barcode on DNA from the phage T4 that captures its circular permutation and agrees well with its known sequence.
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4.
  • Persson, Fredrik, et al. (författare)
  • USING SIMULATION TO DETERMINE THE SAFETY STOCK LEVEL FOR INTERMITTENT DEMAND
  • 2017
  • Ingår i: 2017 WINTER SIMULATION CONFERENCE (WSC). - : IEEE. - 9781538634288 ; , s. 3768-3779
  • Konferensbidrag (refereegranskat)abstract
    • Safety stock calculations are difficult for products with intermittent demand, long production lead times, and high monetary values. Theoretically, forecasts can be used to reduce the need for safety stocks. A high precision forecast minimizes the need for safety stock and forecast evaluation measurements can be used to calculate the safety stock level. However, a more realistic determination of safety stock levels can he obtained by simulation. In this paper, simulation is used to model and experiment on a case with three end products in order to determine the relationship between safety stock levels and service levels. Also, a comparison is made with theoretically calculated safety stocks to see how well basic theoretical models for safety stock calculations fulfill the requirements of service level. The result is that simulation can provide a much more accurate determination of safety stock levels for intermittent demands than theoretical calculations.
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5.
  • Alizadehheidari, Mohammadreza, et al. (författare)
  • Nanoconfined Circular and Linear DNA: Equilibrium Conformations and Unfolding Kinetics
  • 2015
  • Ingår i: Macromolecules. - : The American Chemical Society (ACS). - 0024-9297 .- 1520-5835. ; 48:3, s. 871-878
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies of circular DNA confined to nanofluidic channels are relevant both from a fundamental polymer-physics perspective and due to the importance of circular DNA molecules in vivo. We here observe the unfolding of confined DNA from the circular to linear configuration as a light-induced double-strand break occurs, characterize the dynamics, and compare the equilibrium conformational statistics of linear and circular configurations. This is important because it allows us to determine to what extent existing statistical theories describe the extension of confined circular DNA. We find that the ratio of the extensions of confined linear and circular DNA configurations increases as the buffer concentration decreases. The experimental results fall between theoretical predictions for the extended de Gennes regime at weaker confinement and the Odijk regime at stronger confinement. We show that it is possible to directly distinguish between circular and linear DNA molecules by measuring the emission intensity from the DNA. Finally, we determine the rate of unfolding and show that this rate is larger for more confined DNA, possibly reflecting the corresponding larger difference in entropy between the circular and linear configurations.
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6.
  • Alizadehheidari, Mohammadreza, et al. (författare)
  • Nanoconfined Circular DNA
  • 2014
  • Ingår i: Biophysical Journal. - 0006-3495 .- 1542-0086. ; 106:2, s. 274A-274A
  • Tidskriftsartikel (övrigt vetenskapligt)abstract
    • Nanofluidic channels have become a versatile tool to manipulate single DNA molecules. They allow investigation of confined single DNA molecules from a fundamental polymer physics perspective as well as for example in DNA barcoding techniques.
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7.
  • Alizadehheidari, Mohammadreza, 1987, et al. (författare)
  • Unfolding of nanoconfined circular DNA
  • 2015
  • Ingår i: BIOPHYSICAL JOURNAL. - 0006-3495 .- 1542-0086. ; 108:2 Supplement 1, s. 231A-231A
  • Tidskriftsartikel (övrigt vetenskapligt)
  •  
8.
  • Asp, Michaela, et al. (författare)
  • Spatial detection of fetal marker genes expressed at low level in adult human heart tissue
  • 2017
  • Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Heart failure is a major health problem linked to poor quality of life and high mortality rates. Hence, novel biomarkers, such as fetal marker genes with low expression levels, could potentially differentiate disease states in order to improve therapy. In many studies on heart failure, cardiac biopsies have been analyzed as uniform pieces of tissue with bulk techniques, but this homogenization approach can mask medically relevant phenotypes occurring only in isolated parts of the tissue. This study examines such spatial variations within and between regions of cardiac biopsies. In contrast to standard RNA sequencing, this approach provides a spatially resolved transcriptome- and tissue-wide perspective of the adult human heart, and enables detection of fetal marker genes expressed by minor subpopulations of cells within the tissue. Analysis of patients with heart failure, with preserved ejection fraction, demonstrated spatially divergent expression of fetal genes in cardiac biopsies.
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9.
  • Bergström, Göran, 1964, et al. (författare)
  • Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population.
  • 2021
  • Ingår i: Circulation. - Philadelphia : American Heart Association. - 1524-4539 .- 0009-7322. ; 144:12, s. 916-929
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.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.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.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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10.
  • 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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