| 471. |
- Lönnberg, Maria, 1953-
(författare)
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Membrane-Assisted Isoform ImmunoAssay : Separation and determination of protein isoforms
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Proteins exist in a variety of isoforms with minor differences, mostly due to their glycosylation patterns, which can modulate their biological functions. It seems to be of clinical relevance to measure the isoform-distribution.Thesis describes a novel technology named Membrane-Assisted Isoform ImmunoAssay (MAIIA). This technique allows rapid (< 15 min.) isoform determination. It is based on a chromatographic separation combined with immunoassay detection. These steps are performed along a thin, disposable micro-porous chip in which capillary forces maintain the flow. By using anion-exchange as a chromatographic principle the technology has been utilized for the determination of transferrin isoforms in ten minutes. In one variant (the one-dimensional), selected isoforms (carbohydrate-deficient transferrin) are quantified. In a more elaborate variant (the two-dimensional) it was possible to determine the entire isoform profile of transferrin. Isoforms differing by only 0.1 pH unit in isoelectric point could be distinguished.The chromatography along the microporous bed of nitrocellulose showed very good separation performance with plate heights of 10-20 µm and only minor flow rate variations between individual devices. The quantitative determination of antibody-captured molecules was performed by using antibodies labelled with carbon black particles. Combined with a detection procedure by means of a flatbed scanner, a highly sensitive and specific immunoassay with a detection limit of 0.13 pM was obtained upon using IgE as a model analyte.This technology can thus be used to rapidly distinguish proteins with minor structure differences and specifically determine protein isoforms in complex environments, e.g., blood, down in the pM (10-12 M) concentration range.
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| 472. |
- Maasfeh, Lujain, et al.
(författare)
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Impaired Luminal Control of Intestinal Macrophage Maturation in Patients With Ulcerative Colitis During Remission
- 2021
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Ingår i: Cellular and Molecular Gastroenterology and Hepatology. - : Elsevier BV. - 2352-345X. ; 12:4, s. 1415-1432
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Intestinal macrophages adopt a hyporesponsive phenotype through education by local signals. Lack of proper macrophage maturation in patients with ulcerative colitis (UC) in remission may initiate gut inflammation. The aim, therefore, was to determine the effects of fecal luminal factors derived from healthy donors and UC patients in remission on macrophage phenotype and function. METHODS: Fecal supernatants (FS) were extracted from fecal samples of healthy subjects and UC patients in remission. Monocytes were matured into macrophages in the presence of granulocyte-macrophage colony-stimulating factor without/with FS, stimulated with lipopolysaccharide, and macrophage phenotype and function were assessed. Fecal metabolomic profiles were analyzed by gas-chromatography/mass-spectrometry. RESULTS: Fecal luminal factors derived from healthy donors were effective in down-regulating Toll-like receptor signaling, cytokine signaling, and antigen presentation in macrophages. Fecal luminal factors derived from UC patients in remission were less potent in inducing lipopolysaccharide hyporesponsiveness and modulating expression of genes involved in macrophage cytokine and Toll-like receptor signaling pathways. Although phagocytic and bactericidal abilities of macrophages were not affected by FS treatment, healthy FS-treated macrophages showed a greater ability to suppress cluster of differentiation 4(+) T-cell activation and interferon gamma secretion compared with UC remission FS-treated counterparts. Furthermore, metabolomic analysis showed differential fecal metabolite composition for healthy donors and UC patients in remission. CONCLUSIONS: Our data indicate that UC patients in remission lack luminal signals able to condition macrophages toward a hyporesponsive and tolerogenic phenotype, which may contribute to their persistent vulnerability to relapse.
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| 473. |
- Madsen, I. E. H., et al.
(författare)
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Job strain as a risk factor for clinical depression : systematic review and meta-analysis with additional individual participant data
- 2017
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Ingår i: Psychological Medicine. - : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 47:8, s. 1342-1356
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Forskningsöversikt (refereegranskat)abstract
- Background. Adverse psychosocial working environments characterized by job strain (the combination of high demands and low control at work) are associated with an increased risk of depressive symptoms among employees, but evidence on clinically diagnosed depression is scarce. We examined job strain as a risk factor for clinical depression. Method. We identified published cohort studies from a systematic literature search in PubMed and PsycNET and obtained 14 cohort studies with unpublished individual-level data from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium. Summary estimates of the association were obtained using random-effects models. Individual-level data analyses were based on a pre-published study protocol. Results. We included six published studies with a total of 27 461 individuals and 914 incident cases of clinical depression. From unpublished datasets we included 120 221 individuals and 982 first episodes of hospital-treated clinical depression. Job strain was associated with an increased risk of clinical depression in both published [relative risk (RR) = 1.77, 95% confidence interval (CI) 1.47-2.13] and unpublished datasets (RR = 1.27, 95% CI 1.04-1.55). Further individual participant analyses showed a similar association across sociodemographic subgroups and after excluding individuals with baseline somatic disease. The association was unchanged when excluding individuals with baseline depressive symptoms (RR = 1.25, 95% CI 0.94-1.65), but attenuated on adjustment for a continuous depressive symptoms score (RR = 1.03, 95% CI 0.81-1.32). Conclusions. Job strain may precipitate clinical depression among employees. Future intervention studies should test whether job strain is a modifiable risk factor for depression.
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| 474. |
- Madsen, Ida E.H., et al.
(författare)
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Study protocol for examining job strain as a risk factor for severe unipolar depression in an individual participant meta-analysis of 14 European cohorts
- 2014
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Ingår i: F1000 Research. - : F1000 Research Ltd. - 2046-1402. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous studies have shown that gainfully employed individuals with high work demands and low control at work (denoted "job strain") are at increased risk of common mental disorders, including depression. Most existing studies have, however, measured depression using self-rated symptom scales that do not necessarily correspond to clinically diagnosed depression. In addition, a meta-analysis from 2008 indicated publication bias in the field.Methods: This study protocol describes the planned design and analyses of an individual participant data meta-analysis, to examine whether job strain is associated with an increased risk of clinically diagnosed unipolar depression based on hospital treatment registers. The study will be based on data from approximately 120,000 individuals who participated in 14 studies on work environment and health in 4 European countries. The self-reported working conditions data will be merged with national registers on psychiatric hospital treatment, primarily hospital admissions. Study-specific risk estimates for the association between job strain and depression will be calculated using Cox regressions. The study-specific risk estimates will be pooled using random effects meta-analysis.Discussion: The planned analyses will help clarify whether job strain is associated with an increased risk of clinically diagnosed unipolar depression. As the analysis is based on pre-planned study protocols and an individual participant data meta-analysis, the pooled risk estimates will not be influenced by selective reporting and publication bias. However, the results of the planned study may only pertain to severe cases of unipolar depression, because of the outcome measure applied.
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| 475. |
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| 476. |
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| 477. |
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| 478. |
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| 479. |
- Magnusson, Carl, 1976, et al.
(författare)
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Suboptimal prehospital decision- making for referral to alternative levels of care - frequency, measurement, acceptance rate and room for improvement
- 2022
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Ingår i: Bmc Emergency Medicine. - : Springer Science and Business Media LLC. - 1471-227X. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The emergency medical services (EMS) have undergone dramatic changes during the past few decades. Increased utilisation, changes in care-seeking behaviour and competence among EMS clinicians have given rise to a shift in EMS strategies in many countries. From transport to the emergency department to at the scene deciding on the most appropriate level of care and mode of transport. Among the non-conveyed patients some may suffer from "time-sensitive conditions" delaying diagnosis and treatment. Thus, four questions arise: How often are time-sensitive cases referred to primary care or self-care advice? How can we measure and define the level of inappropriate clinical decision-making? What is acceptable? How to increase patient safety? Main text To what extent time-sensitive cases are non-conveyed varies. About 5-25% of referred patients visit the emergency department within 72 hours, 5% are hospitalised, 1-3% are reported to have a time-sensitive condition and seven-day mortality rates range from 0.3 to 6%. The level of inappropriate clinical decision-making can be measured using surrogate measures such as emergency department attendances, hospitalisation and short-term mortality. These measures do not reveal time-sensitive conditions. Defining a scoring system may be one alternative, where misclassifications of time-sensitive cases are rated based on how severely they affected patient outcome. In terms of what is acceptable there is no general agreement. Although a zero-vision approach does not seem to be realistic unless under-triage is split into different levels of severity with zero-vision in the most severe categories. There are several ways to reduce the risk of misclassifications. Implementation of support systems for decision-making using machine learning to improve the initial assessment is one approach. Using a trigger tool to identify adverse events is another. Conclusion A substantial number of patients are non-conveyed, including a small portion with time-sensitive conditions. This poses a threat to patient safety. No general agreement on how to define and measure the extent of such EMS referrals and no agreement of what is acceptable exists, but we conclude an overall zero-vision is not realistic. Developing specific tools supporting decision making regarding EMS referral may be one way to reduce misclassification rates.
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| 480. |
- Magnusson, Daniel, 1978, et al.
(författare)
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Demonstration of a SANEX process in centrifugal contactors using the CyMe4-BTBP molecule on a genuine fuel solution
- 2009
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Ingår i: Solvent Extraction and Ion Exchange. - : Informa UK Limited. - 0736-6299 .- 1532-2262. ; 27:2, s. 97-106
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Tidskriftsartikel (refereegranskat)abstract
- Efficient recovery of minor actinides from a genuine spent fuel solution has been successfully demonstrated by the CyMe4-BTBP/DMDOHEMA extractant mixture dissolved in octanol. The continuous countercurrent process, in which actinides(III) were separated from lanthanides(III), was carried out in laboratory centrifugal contactors using an optimized flow-sheet involving a total of 16 stages. The process was divided into 9 stages for extraction from a 2 M nitric acid feed solution, 3 stages for lanthanide scrubbing, and 4 stages for actinide back-extraction. Excellent feed decontamination factors for Am (7000) and Cm (1000) were obtained and the recoveries of these elements were higher than 99.9%. More than 99.9% of the lanthanides were directed to the raffinate except Gd for which 0.32% was recovered in the product.
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