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| 2. |
- Barkholt, L, et al.
(författare)
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Safety analysis of ex vivo-expanded NK and NK-like T cells administered to cancer patients: a phase I clinical study
- 2009
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Ingår i: Immunotherapy. - : Future Medicine Ltd. - 1750-7448 .- 1750-743X. ; 1:5, s. 753-764
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Tidskriftsartikel (refereegranskat)abstract
- The chimeric state after allogeneic hematopoietic stem cell transplantation provides a platform for adoptive immunotherapy using donor-derived immune cells. The major risk with donor lymphocyte infusions (DLIs) is the development of graft-versus-host disease (GvHD). Development of new DLI products with antitumor reactivity and reduced GvHD risk represents a challenging task in cancer immunotherapy. Although natural killer (NK) and NK-like T cells are promising owing to their antitumor activity, their low concentrations in peripheral blood mononuclear cells reduces their utility in DLIs. We have recently developed a system that allows expansion of clinical-grade NK and NK-like T cells in large numbers. In this study, the safety of donor-derived long-term ex vivo-expanded human NK and NK-like T cells given as DLIs was investigated as immunotherapy for cancer in five patients following allogeneic stem cell infusion. Infusion of the cells was safe whether administered alone or with IL-2 subcutaneously. No signs of acute GvHD were observed. One patient with hepatocellular carcinoma showed markedly decreased serum α-fetoprotein levels following cell infusions. These findings suggest that the use of ex vivo-expanded NK and NK-like T cells is safe and appears an attractive approach for further clinical evaluation in cancer patients.
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| 3. |
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| 4. |
- Bergman, T, et al.
(författare)
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C-terminal sequence analysis
- 2003
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Ingår i: Current protocols in protein science. - : Wiley. - 1934-3663 .- 1934-3655. ; Chapter 11, s. 11.8-
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Tidskriftsartikel (refereegranskat)
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| 10. |
- Arlander, E, et al.
(författare)
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No volume effect on retrograde colonic spread of rectally-administered ropivacaine gel
- 2003
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 18:6, s. 655-660
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Tidskriftsartikel (refereegranskat)abstract
- Background: Rectal administration of enemas, foams and suppositories is the most efficient way to deliver locally acting drugs to the distal colon. Ropivacaine, a long-acting local anaesthetic, was chosen as a candidate for a new rectal treatment of ulcerative colitis. Aim: To determine the colonic spread of a rectal ropivacaine formulation. Methods: In this randomized, incomplete cross-over study, 12 male volunteers were given 200 mg ropivacaine HCl rectally in 20, 40, 60 and 80 mL hydroxypropyl methylcellulose gel. The viscosity of the gel was 1.1 Pa s. The spread of the radiolabelled ( 99mTc-labelled diethylenetriaminepenta-acetic acid) formulations was assessed by gamma-scintigraphy. Plasma was collected and analysed for ropivacaine base. Results: The retrograde spread was limited to the descending colon and the difference between the studied volumes was not statistically significant. Only the 80-mL volume tended to have a larger distribution, although the 20-mL volume showed the same maximal distribution in two subjects. No distinct relationship between volume, retrograde colonic spread and plasma concentrations could be found. Ropivacaine was well tolerated. Conclusions: Rectal ropivacaine gel in all volumes between 20 and 80 mL can spread up to the descending colon. There was no relationship between either retrograde colonic spread or the administered volume and the ropivacaine plasma concentrations.
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| 11. |
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| 12. |
- Bergström, Göran, et al.
(författare)
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Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
- 2021
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Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
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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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| 13. |
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| 14. |
- Cederlund, A, et al.
(författare)
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Label-free quantitative mass spectrometry reveals novel pathways involved in LL-37 expression
- 2014
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Ingår i: Journal of innate immunity. - : S. Karger AG. - 1662-8128 .- 1662-811X. ; 6:3, s. 365-376
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial peptides are important for a healthy host-microbe homeostasis. In infections characterized by low levels of the human cathelicidin, LL-37, induction of its expression increases clearance of pathogens. Our aim was to discover signaling pathways and compounds capable of affecting the expression of LL-37. We recently observed a synergistic induction of LL-37 expression by stimulating the colonic epithelial cell-line HT-29 with lactose and phenylbutyrate (PBA). Here, we studied regulatory circuits mediating this synergism in HT-29 cells stimulated with lactose (60 g/l) and PBA (2 m<smlcap>M</smlcap>) for 24 h by using mass spectrometry and pathway analyses. Selected pathways were evaluated for their involvement in LL-37 regulation in a <i>CAMP</i> gene-luciferase reporter system. Three pathways were examined in detail: thyroid hormone receptor and retinoid X receptor (TR/RXR) activation, eicosanoid signaling and steroid biosynthesis. Induced expression of LL-37 was observed upon stimulation with triiodothyronine (T3, 2.5 n<smlcap>M</smlcap>-1 µ<smlcap>M</smlcap> for 3-30 h) and thyroxine (T4, 2.5-10 n<smlcap>M</smlcap> for 24 h). Furthermore, the synergism of lactose and PBA was reduced in cells coincubated with inhibitors of phospholipase A2, cyclooxygenase 2 or HMG-CoA reductase. Based on these results, we conclude that proteomics and pathway analyses are valuable tools for dissecting the regulatory networks involved in LL-37 expression.
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| 19. |
- Cederlund, K, et al.
(författare)
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Visual grading of emphysema severity in candidates for lung volume reduction surgery. Comparison between HRCT, spiral CT and "density-masked" images
- 2002
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Ingår i: Acta radiologica (Stockholm, Sweden : 1987). - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 43:1, s. 48-53
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate which of three types of CT imaging yielded the best results in estimating the degree of emphysema in patients undergoing evaluation for lung volume reduction surgery (LVRS), whether there was any difference in this regard between the cranial and caudal part of the lung, and whether the degree of emphysema had an impact on the estimation. Material and Methods: Four radiologists visually classified different degrees of emphysema on three different types of CT images into four groups. The degree of emphysema was calculated by a computer. The three types of images were as follows: HRCT images (2-mm slice thickness); spiral CT images (10-mm slice thickness); and density-masked images (spiral CT images printed with pixels below -960 HU, depicted in white). Results: The conventionally presented images from HRCT and spiral CT yielded the same results (60% respective 62% correct classifications) in assessing the degree of emphysema irrespective of localisation. Significantly improved results were obtained when the spiral CT images were presented as density-masked images (74%). Conclusion: There was no difference between HRCT and spiral CT in assessing the degree of emphysema in candidates for LVRS. Improvement can be achieved by the use of density-masked images.
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| 20. |
- Cederlund, Martin, et al.
(författare)
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A1M/α1-microglobulin is proteolytically activated by myeloperoxidase, binds its heme group and inhibits low density lipoprotein oxidation.
- 2015
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- α1-microglobulin (A1M) is a 26 kDa plasma and tissue protein with reductase activity and radical- and heme-binding anti-oxidative functions. In addition, exposure of A1M to hemoglobin has been shown to induce proteolytic elimination of a C-terminal tetrapeptide yielding a heme-degrading form, truncated A1M (t-A1M). Myeloperoxidase (MPO), a heme-containing enzyme that catalyzes the production of free radicals and hypochlorite, is released by neutrophils during the inflammatory response to bacterial infections. MPO-induced low density lipoprotein (LDL)-oxidation in blood has been suggested as a causative factor in atherosclerosis. In this study we have hypothesized that A1M interacts with MPO in a similar mode as with hemoglobin, and is a regulator of its activity. The results show that A1M is proteolytically cleaved, with formation of t-A1M, after exposure to MPO, and that t-A1M contains iron and heme-degradation products. The reaction is dependent of pH, time and concentration of substrates and a pH-value around 7 is shown to be optimal for cleavage. Furthermore, A1M inhibits MPO- and hydrogen peroxide-induced oxidation of LDL. The results suggest that A1M may have a role as an inhibitor of the damaging effects of the neutrophil respiratory burst on bystander tissue components.
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| 21. |
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| 23. |
- Dahle, B., et al.
(författare)
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Predation on adult moose Alces alces by European brown bears Ursus arctos
- 2013
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Ingår i: Wildlife Biology. - : Wiley. - 0909-6396 .- 1903-220X. ; 19:2, s. 165-169
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Tidskriftsartikel (refereegranskat)abstract
- Several North American studies have reported significant predation rates on moose Alces alces by brown bears Ursus arctos. We documented predation on moose by brown bears in south-central Sweden, where brown bears and moose occurred at estimated densities of 10-30 and 400-1,340/1,000 km(2), respectively. Bears killed 0.8% of radio-collared adult female moose (i.e. >= 1 year old) annually and no male moose (>= 1 year old). Bear predation was the least important mortality factor we documented. Based on tracking brown bears on snow during spring we recorded one successful hunt for every 372 km of tracks and documented attacks only by adult bears and successful attacks only by adult males. Autopsy of moose older than calves that were killed by brown bears revealed that yearlings were more prone to predation than older moose, and that older (i.e. >= 2 years) cows were more vulnerable to predation than older bulls. Our study suggests a lower tendency for Scandinavian brown bears to prey on moose compared to most of the North American studies.
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| 24. |
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| 26. |
- Gram, Magnus, et al.
(författare)
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Up-Regulation of A1M/α(1)-Microglobulin in Skin by Heme and Reactive Oxygen Species Gives Protection from Oxidative Damage.
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- During bleeding the skin is subjected to oxidative insults from free heme and radicals, generated from extracellular hemoglobin. The lipocalin α(1)-microglobulin (A1M) was recently shown to have reductase properties, reducing heme-proteins and other substrates, and to scavenge heme and radicals. We investigated the expression and localization of A1M in skin and the possible role of A1M in the protection of skin tissue from damage induced by heme and reactive oxygen species. Skin explants, keratinocyte cultures and purified collagen I were exposed to heme, reactive oxygen species, and/or A1M and investigated by biochemical methods and electron microscopy. The results demonstrate that A1M is localized ubiquitously in the dermal and epidermal layers, and that the A1M-gene is expressed in keratinocytes and up-regulated after exposure to heme and reactive oxygen species. A1M inhibited the heme- and reactive oxygen species-induced ultrastructural damage, up-regulation of antioxidation and cell cycle regulatory genes, and protein carbonyl formation in skin and keratinocytes. Finally, A1M bound to purified collagen I (K(d) = 0.96×10(-6) M) and could inhibit and repair the destruction of collagen fibrils by heme and reactive oxygen species. The results suggest that A1M may have a physiological role in protection of skin cells and matrix against oxidative damage following bleeding.
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| 27. |
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| 28. |
- Hirschberg, Daniel, et al.
(författare)
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N-terminal acetylation in a third protein family of vertebrate alcohol dehydrogenase/retinal reductase found through a 'proteomics' approach in enzyme characterization.
- 2001
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Ingår i: Cellular and Molecular Life Sciences (CMLS). - 1420-682X .- 1420-9071. ; 58:9
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Tidskriftsartikel (refereegranskat)abstract
- A recent finding of a novel class of retinol-active alcohol dehydrogenase (ADH) in frog prompted analysis of this activity in other vertebrate forms. Surprisingly, yet another and still more unrelated ADH was identified in chicken tissues. It was found to be a member of the aldo-keto reductase (AKR) enzyme family, not previously known as an ADH in vertebrates. Its terminal blocking group and the N-terminal segment, not assigned by protein and cDNA structure analysis, were determined by electrospray tandem mass spectrometry after protein isolation by two-dimensional gel electrophoresis. The N terminus is Acetyl-Ala- and the N-terminal segment contains two consecutive Asn residues. The results establish the new ADH enzyme of the AKR family and show the usefulness of combined gel separation and mass spectrometry in enzyme-characterization.
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| 29. |
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| 30. |
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| 31. |
- Markovic, O, et al.
(författare)
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Characterization of carrot pectin methylesterase
- 2002
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Ingår i: Cellular and molecular life sciences : CMLS. - : Springer Science and Business Media LLC. - 1420-682X .- 1420-9071. ; 59:3, s. 513-518
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Tidskriftsartikel (refereegranskat)
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| 32. |
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| 36. |
- Nylen, F, et al.
(författare)
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Boosting innate immunity: development and validation of a cell-based screening assay to identify LL-37 inducers
- 2014
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Ingår i: Innate immunity. - : SAGE Publications. - 1753-4267 .- 1753-4259. ; 20:4, s. 364-376
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Tidskriftsartikel (refereegranskat)abstract
- Innate immunity, the front line of our defence against pathogens, relies, to a great extent, on the production of antimicrobial peptides (AMPs). These peptides exhibit antimicrobial activity and immunomodulatory properties. In humans, AMPs include the defensins (α- and β-families) and the cathelicidin, LL-37. Bacterial resistance against antibiotics is a growing concern, and novel antimicrobial strategies are needed urgently. Hence, the concept of strengthening immune defences against infectious microbes by inducing AMP expression may represent novel or complementary pharmaceutical interventions in the treatment or prevention of infections. We have developed and validated a robust cell-based reporter assay for LL-37 expression, which serves as a marker for a healthy epithelial barrier. This reporter assay can be a powerful tool for high-throughput screenings. We first employed our assay to screen a panel of histone deacetylase inhibitors and derivatives, and then the Prestwick Chemical Library of Food and Drug Administration-approved compounds. After hit confirmation and independent validation in the parental cell line we identified five novel inducers of LL-37. This reporter assay will help to identify novel drug candidates for the treatment and prevention of infections. Importantly, the pattern of hits obtained may suggest cellular pathways and key mediators involved in the regulation of AMP expression.
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| 37. |
- Odéus, Ellen, et al.
(författare)
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Weighted blankets for sleep problems - prescription, use and cost analysis
- 2023
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Ingår i: Scandinavian Journal of Occupational Therapy. - : Informa UK Limited. - 1103-8128 .- 1651-2014. ; 30:2, s. 211-221
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Tidskriftsartikel (refereegranskat)abstract
- Background Weighted blankets (WBs) have been suggested as a treatment option for insomnia and are commonly prescribed despite lack of evidence of efficacy. Aim To investigate prescription pattern, return rate and cost of WBs. Material and methods This observational cohort register-based study in western Sweden included every individual who, in a 2.5-year period, was prescribed and received at least one WB (n = 4092). A cost evaluation was made by mapping prescription processes for WBs and sleep medication. Results Individuals diagnosed with dementia, anxiety, autism or intellectual disability (ID) retained the WB longer than others. Individuals younger than six and older than 65 years had shorter use time. The cost evaluation showed that the prescription process for WBs was longer and resulted in a higher cost than for sleep medication. Conclusions Some individuals had longer use time, indicating a possible benefit from using a WB. Due to low risk of harm but high economic cost, a revision of the WBs prescription process could be recommended to identify those who might benefit from WB. Significance Our result points towards a need for revision of the prescription process, to implement standardized sleep assessments, and create a more efficient prescription process to lower the cost.
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| 38. |
- Ollendick, Thomas, H., et al.
(författare)
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One-Session Treatment of Specific Phobias in Youth : A Randomized Clinical Trial in the United States and Sweden
- 2009
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Ingår i: Journal of Consulting and Clinical Psychology. - : American Psychological Association (APA). - 0022-006X .- 1939-2117. ; 77:3, s. 504-509
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Tidskriftsartikel (refereegranskat)abstract
- One hundred and ninety-six youth, ages 7–16, who fulfilled Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria for various specific phobias were randomized to a one-session exposure treatment, education support treatment, or a wait list control group. After the waiting period, the wait list participants were offered treatment and, if interested, rerandomized to 1 of the 2 active treatments. The phobias were assessed with semistructured diagnostic interviews, clinician severity ratings, and behavioral avoidance tests, whereas fears, general anxiety, depression, and behavior problems were assessed with self- and parent report measures. Assessments were completed pretreatment, posttreatment, and at 6 months following treatment. Results showed that both treatment conditions were superior to the wait list control condition and that 1-session exposure treatment was superior to education support treatment on clinician ratings of phobic severity, percentage of participants who were diagnosis free, child ratings of anxiety during the behavioral avoidance test, and treatment satisfaction as reported by the youth and their parents. There were no differences on self-report measures. Treatment effects were maintained at follow-up. Implications of these findings are discussed.
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| 39. |
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| 40. |
- Pesonen, Ida, et al.
(författare)
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High prevalence of interstitial lung abnormalities in middle-aged never-smokers
- 2023
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Ingår i: ERJ Open Research. - : European Respiratory Society. - 2312-0541. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Interstitial lung abnormalities (ILA) are incidental findings on chest computed tomography (CT). These patterns can present at an early stage of fibrotic lung disease. Our aim was to estimate the prevalence of ILA in the Swedish population, in particular in never-smokers, and find out its association with demographics, comorbidities and symptoms.METHODS: Participants were recruited to the Swedish CArdioPulmonary BioImage Study (SCAPIS), a population-based survey including men and women aged 50-64 years performed at six university hospitals in Sweden. CT scan, spirometry and questionnaires were performed. ILA were defined as cysts, ground-glass opacities, reticular abnormality, bronchiectasis and honeycombing.FINDINGS: Out of 29 521 participants, 14 487 were never-smokers and 14 380 were men. In the whole population, 2870 (9.7%) had ILA of which 134 (0.5%) were fibrotic. In never-smokers, the prevalence was 7.9% of which 0.3% were fibrotic. In the whole population, age, smoking history, chronic bronchitis, cancer, coronary artery calcium score and high-sensitive C-reactive protein were associated with ILA. Both ILA and fibrotic ILA were associated with restrictive spirometric pattern and impaired diffusing capacity of the lung for carbon monoxide. However, individuals with ILA did not report more symptoms compared with individuals without ILA.INTERPRETATION: ILA are common in a middle-aged Swedish population including never-smokers. ILA may be at risk of being underdiagnosed among never-smokers since they are not a target for screening.
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| 41. |
- Ripsweden, J, et al.
(författare)
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Is training essential for interpreting cardiac computed tomography?
- 2009
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Ingår i: Acta radiologica (Stockholm, Sweden : 1987). - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 50:2, s. 194-200
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cardiac computed tomography (CT) has gained increasing acceptance for diagnosing obstructive coronary artery disease (CAD). Several guidelines have been published on required education for proficiency in the interpretation of these examinations. Purpose: To describe the learning-curve effect of the interpretation of 100 consecutive cardiac CT examinations aimed at diagnosing CAD. The diagnostic accuracy of radiologists and radiographers was also compared. Material and Methods: Two radiologists and two radiographers, all with no prior experience in evaluation of cardiac CT, independently underwent a dedicated training program of 100 examinations randomized into 10 blocks (sessions), with 10 cases in each. They independently evaluated the coronary arteries regarding significant obstructive CAD. After every session, individual feedback on diagnostic accuracy and comparison with the corresponding invasive coronary angiography (currently regarded as the gold standard to detect coronary lesions) was given. The time required for interpretation was recorded. Results: The mean review time decreased ( P<0.0001) successively during the 10 sessions for all the observers together. The first session had a mean review time of 32 min, and the last session 16 min. No significant improvement in sensitivity, specificity, or negative predictive value (NPV) was observed. For positive predictive value (PPV), there was an improvement for the radiologists ( P<0.05), but not for the radiographers. The radiographers had a higher total specificity compared to the radiologists ( P<0.01). Conclusion: The review time for novices in cardiac CT was approximately halved during the first 100 cases, with maintained accuracy. There was a learning-curve effect in PPV for the radiologists. The diagnostic accuracy of dedicated radiographers indicates that they might be considered to be included as part of the evaluation team.
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