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- Bredewold, Obbo W, et al.
(författare)
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Cardiovascular Risk Following Conversion to Belatacept From a Calcineurin Inhibitor in Kidney Transplant Recipients : A Randomized Clinical Trial
- 2023
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Ingår i: Kidney Medicine. - : Elsevier. - 2590-0595. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE & OBJECTIVE: In kidney transplant recipients (KTRs), a belatacept-based immunosuppressive regimen is associated with beneficial effects on cardiovascular (CV) risk factors compared with calcineurin inhibitor (CNI)-based regimens. Our objective was to compare the calculated CV risk between belatacept and CNI (predominantly tacrolimus) treatments using a validated model developed for KTRs.STUDY DESIGN: Prospective, randomized, open-label, parallel-group, investigator-initiated, international multicenter trial.SETTING & PARTICIPANTS: KTRs aged 18-80 years with a stable graft function (estimated glomerular filtration rate > 20 mL/min/1.73 m2), 3-60 months after transplantation, treated with tacrolimus or cyclosporine A, were eligible for inclusion.INTERVENTION: Continuation with a CNI-based regimen or switch to belatacept for 12 months.OUTCOMES: Comparison of the change in the estimated 7-year risk of major adverse CV events and all-cause mortality, changes in traditional markers of CV health, as well as measures of arterial stiffness.RESULTS: Among the 105 KTRs randomized, we found no differences between the treatment groups in the predicted risk for major adverse CV events or mortality. Diastolic blood pressure, measured both centrally by using a SphygmoCor device and peripherally, was lower after the belatacept treatment than after the CNI treatment. The mean changes in traditional cardiovascular (CV) risk factors, including kidney transplant function, were otherwise similar in both the treatment groups. The belatacept group had 4 acute rejection episodes; 2 were severe rejections, of which 1 led to graft loss.LIMITATIONS: The heterogeneous baseline estimated glomerular filtration rate and time from transplantation to trial enrollment in the participants. A limited study duration of 1 year.CONCLUSIONS: We found no effects on the calculated CV risk by switching to the belatacept treatment. Participants in the belatacept group had not only lower central and peripheral diastolic blood pressure but also a higher rejection rate.FUNDING: The trial has received a financial grant from Bristol-Myers Squibb.TRIAL REGISTRATION: EudraCT no. 2013-001178-20.
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2. |
- Chorell, Elin, et al.
(författare)
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A Multivariate Screening Strategy for Investigating Metabolic Effects of Strenuous Physical Exercise in Human Serum
- 2007
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Ingår i: Journal of Proteome Research. - : American Chemical Society. - 1535-3893 .- 1535-3907. ; 6:6, s. 2113-2120
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Tidskriftsartikel (refereegranskat)abstract
- A novel hypothesis-free multivariate screening methodology for the study of human exercise metabolism in blood serum is presented. Serum gas chromatography/time-of-flight mass spectrometry (GC/TOFMS) data was processed using hierarchical multivariate curve resolution (H-MCR), and orthogonal partial least-squares discriminant analysis (OPLS-DA) was used to model the systematic variation related to the acute effect of strenuous exercise. Potential metabolic biomarkers were identified using data base comparisons. Extensive validation was carried out including predictive H-MCR, 7-fold full cross-validation, and predictions for the OPLS-DA model, variable permutation for highlighting interesting metabolites, and pairwise t tests for examining the significance of metabolites. The concentration changes of potential biomarkers were verified in the raw GC/TOFMS data. In total, 420 potential metabolites were resolved in the serum samples. On the basis of the relative concentrations of the 420 resolved metabolites, a valid multivariate model for the difference between pre- and post-exercise subjects was obtained. A total of 34 metabolites were highlighted as potential biomarkers, all statistically significant (p < 8.1E-05). As an example, two potential markers were identified as glycerol and asparagine. The concentration changes for these two metabolites were also verified in the raw GC/TOFMS data.The strategy was shown to facilitate interpretation and validation of metabolic interactions in human serum as well as revealing the identity of potential markers for known or novel mechanisms of human exercise physiology. The multivariate way of addressing metabolism studies can help to increase the understanding of the integrative biology behind, as well as unravel new mechanistic explanations in relation to, exercise physiology.
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4. |
- Engkvist, Inga-Lill, et al.
(författare)
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Joint investigation of working conditions, environmental and system performance at recycling centres : Development of instruments and their usage
- 2010
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Ingår i: Applied Ergonomics. - : Elsevier BV. - 0003-6870 .- 1872-9126. ; 41:3, s. 336-346
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Tidskriftsartikel (refereegranskat)abstract
- Recycling is a new and developing industry, which has only been researched to a limited extent. This article describes the development and use of instruments for data collection within a multidisciplinary research programme "Recycling centres in Sweden - working conditions, environmental and system performance". The overall purpose of the programme was to form a basis for improving the function of recycling centres with respect to these three perspectives and the disciplines of: ergonomics, safety, external environment, and production systems. A total of 10 instruments were developed for collecting data from employees, managers and visitors at recycling centres. including one instrument for observing visitors. Validation tests were performed in several steps. This, along with the quality of the collected data, and experience from the data collection, showed that the instruments and methodology used were valid and suitable for their purpose.
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5. |
- Engkvist, Inga-Lill, et al.
(författare)
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Reported occupational injuries at Swedish recycling centres - based on official statistics
- 2011
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Ingår i: Ergonomics. - : Informa UK Limited. - 0014-0139 .- 1366-5847. ; 54:4, s. 357-366
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Tidskriftsartikel (refereegranskat)abstract
- Swedish recycling centres are manned facilities for waste collection. There is no special category in the official injury statistics for employees at recycling centres, which precludes a straightforward analysis of reported occupational injuries. This study aimed at identifying the frequency of reported accidents and diseases and the type of events that contribute to such injuries at recycling centres, based on official injury statistics. The employees were identified as being affected by more than three to five times as many accidents compared with the total workforce in Sweden. The reported accidents had occurred during a wide range of situations, but most frequently during manual handling of waste. Reported work-related diseases were mostly associated with musculoskeletal disorders, mainly due to heavy lifting. A more detailed classification of sanitation professions and workplaces in the official injury statistics would facilitate future studies of injuries in a specific professional category, e.g. employees at recycling centres. Suggestions for prevention are given. Statement of Relevance: The present article describes all reported work accidents and diseases among employees at recycling centres from 1992 to February 2005. It also highlights the problem of identifying new working groups in the official statistics and gives advice for a detailed classification to facilitate such future studies of injuries.
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- Engvall, Inga-Lill, et al.
(författare)
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Impact of low-dose prednisolone on bone synthesis and resorption in early rheumatoid arthritis: experiences from a two-year randomized study
- 2008
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Patients with rheumatoid arthritis (RA) have an increased frequency of osteoporosis, mainly because of increased bone resorption. Reduction of disease activity is suggested to reduce bone remodelling. It might also be possible that prednisolone treatment could cause this effect because prednisolone has been shown to arrest the development of joint destruction in early RA. Therefore, we examined the effects of low-dose prednisolone on serum concentrations of bone remodelling markers and insulin-like growth factor-1 (IGF-1) in RA patients in relation to bone mineral density. Methods One hundred and fifty patients, 67% women, with early RA, mean disease duration of six months (95% confidence interval (CI) = three to eight months), who had participated in the BARFOT (Better Anti-Rheumatic FarmacOTherapy) low-dose prednisolone study were included. They had been randomised to either the P-group, who were treated with 7.5 mg prednisolone daily (n = 70, mean age = 51 years, 95% CI 48 to 54 years), or the NoP-group, who received no prednisolone (n = 80, mean age 58 years, 95% CI 56 to 61 years), when they started their first disease-modifying anti-rheumatic drug (DMARD). Serum samples were analysed at baseline, 3 and 12 months for procollagen type I N-terminal propeptide (P1NP), a marker of bone formation, and the C-telopeptide crosslaps of type I collagen (CTX-1) and C-terminal telopeptide of type I collagen (1CTP), markers of bone degradation. IGF-1 was analysed at baseline and after 12 months. Bone mineral density at the lumbar spine and femoral neck was assessed by dual-energy X-ray absorptiometry at baseline and after 24 months. Results Levels of P1NP decreased rapidly in the P-group (p < 0.001). Levels of CTX-1 and 1CTP decreased in both treatment groups, but significantly more in the P-group (differences between groups p < 0.019 and p < 0.001, respectively). IGF-1 increased in the P-group (p < 0.001) but remained stable in the NoP-group. Bone mineral density decreased in the spine in both groups, significantly more in postmenopausal women from the P-group. Femur bone mineral density only decreased in the NoP-group. Conclusions Low-dose prednisolone in early RA counteracts the negative impact of rheumatoid inflammation on bone tissue in the hip, a juxta-articular localisation. Thus bone mineral density was preserved in the femur in the P-group and 1CTP decreased rapidly. However, the systemic inflammatory consequences on bone could not be prevented in the lumbar spine, especially not in postmenopausal women, probably because of the combined effect of suppression of bone synthesis by prednisolone and the postmenopausal status.
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7. |
- Engvall, Inga-Lill, et al.
(författare)
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Low-dose prednisolone in early rheumatoid arthritis inhibits collagen type I degradation by matrix metalloproteinases as assessed by serum 1CTP--a possible mechanism for specific inhibition of radiological destruction
- 2013
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 52:4, s. 733-742
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study the effects of low-dose prednisolone on the osteoclast-regulating proteins osteoprotegerin (OPG) and RANK ligand (RANKL) and on markers of bone resorption, 1CTP generated by MMPs and CTX-1 generated by cathepsin K, in patients with early RA in relation to inflammation and joint destruction.METHODS: In 225 patients, who at the start of the first DMARD had been randomized to 7.5 mg prednisolone daily for 2 years, the P-group, or no prednisolone, the NoP-group, OPG and RANKL were analysed at 0-24 months and 1CTP and CTX-1 at 0-12 months. Radiographs of hands and feet were assessed at 0, 1 and 2 years using the modified Sharp-van der Heijde score and radiological progression defined as increase in total Sharp score above 5.8. Data were analysed with a mixed linear model and by the GENMOD procedure.RESULTS: In the P-group, RANKL and the ratio OPG/RANKL were stable between baseline and 24 months, whereas in the NoP-group, RANKL increased and the ratio OPG/RANKL decreased. CTX-1 decreased significantly more in the P-group. 1CTP decreased over time in both groups, but more in the P-group, P < 0.001, a difference also present in the subgroups of patients in remission. The decrease in 1CTP was associated with less radiological progression after 2 years and displayed a significant interaction with treatment. CONCLUSION: Low-dose prednisolone may inhibit progression of joint destruction by interfering with MMP activity, seen as a marked decrease in 1CTP, as well as by impairing osteoclast activation, shown by a stable OPG/RANKL ratio.
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8. |
- Ericson Lindquist, Kajsa, et al.
(författare)
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Difficulties in diagnostics of lung tumours in biopsies : an interpathologist concordance study evaluating the international diagnostic guidelines
- 2022
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Ingår i: Journal of Clinical Pathology. - : BMJ Publishing Group Ltd. - 0021-9746 .- 1472-4146. ; 75:5, s. 302-309
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Accurate and reliable diagnosis is essential for lung cancer treatment. The study aim was to investigate interpathologist diagnostic concordance for pulmonary tumours according to WHO diagnostic criteria.METHODS: Fifty-two unselected lung and bronchial biopsies were diagnosed by a thoracic pathologist based on a broad spectrum of immunohistochemical (IHC) stainings, molecular data and clinical/radiological information. Slides stained with H&E, thyroid transcription factor-1 (TTF-1) clone SPT24 and p40 were scanned and provided digitally to 20 pathologists unaware of reference diagnoses. The pathologists independently diagnosed the cases and stated if further diagnostic markers were deemed necessary.RESULTS: In 31 (60%) of the cases, ≥80% of the pathologists agreed with each other and with the reference diagnosis. Lower agreement was seen in non-small cell neuroendocrine tumours and in squamous cell carcinoma with diffuse TTF-1 positivity. Agreement with the reference diagnosis ranged from 26 to 45 (50%-87%) for the individual pathologists. The pathologists requested additional IHC staining in 15-44 (29%-85%) of the 52 cases. In nearly half (17 of 36) of the malignant cases, one or more pathologist advocated for a different final diagnosis than the reference without need of additional IHC markers, potentially leading to different clinical treatment.CONCLUSIONS: Interpathologist diagnostic agreement is moderate for small unselected bronchial and lung biopsies based on a minimal panel of markers. Neuroendocrine morphology is sometimes missed and TTF-1 clone SPT24 should be interpreted with caution. Our results suggest an intensified education need for thoracic pathologists and a more generous use of diagnostic IHC markers.
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9. |
- Ericsson, Stina, 1972, et al.
(författare)
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Att analysera interaktion
- 2023
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Snart sagt alla situationer en människa befinner sig i präglas av interaktion. Människor pratar med varandra, rör sig genom ett rum, utbyter blickar, lär sig saker, arbetar, skämtar, håller i föremål ... Utmärkande för oss människor är nämligen att vi får saker och ting gjorda med vårt språk och våra kroppsliga resurser. Genom sådana handlingar påverkar vi vår omvärld och våra medmänniskor - och vi gör det tillsammans med dem. Det är studiet av denna mänskliga interaktion som boken handlar om. I första delen introduceras forskningsfältet interaktionsanalys och de arbetssätt, redskap och etiska ställningstaganden som hör till fältet. Den andra delen innehåller forskningsstudier som visar på bredden inom fältet och som pedagogiskt leder läsaren genom hela analysarbetet. Till boken hör även ett videomaterial som illustrerar några av bokens exempel, och som är tillgängligt för läsarens egna studier. Att analysera interaktion är avsedd för utbildningar inom språk vetenskap och angränsande ämnen som sociologi, utbildningsvetenskap och kommunikation.
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10. |
- Geschwind, Britta Zetterström, 1976-
(författare)
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Publika museirum : Materialiseringar av demokratiska ideal på Statens Historiska Museum 1943-2013
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this dissertation is to investigate how public spaces in the Swedish History Museum in Stockholm have materialized in relation to cultural policy objectives and ideals of a democratic and inclusive museum. The investigated time period spans from 1943 to 2013. The Swedish History Museum is a state-run archaeological museum, where norms and values are expressed through various governmental policy- and control documents. Hence, entering the museum also means entering a symbolic national space. The fact that the museum has been politically regulated throughout the studied period makes it illustrative of changing democratic public ideals in the 20th century.Unlike other similar studies, the empirical focus is not on exhibitions, but on other public spaces that visitors encounter; the entrance, the shop, children’s spaces and the courtyard. These spaces are less invisible in the museum hierarchy. At the same time, they are often central spaces to visitors. The museum building is not as fixed as it might appear to be. Drawing on ideas from Bruno Latour and Doreen Massey – and their perspectives on space, materiality and power – I explore how the social and spatial changes of the museum affect each other. Efforts have continuously been made to alter these public spaces, and the outlines and uses have repeatedly changed.By combining archival materials, interviews and observations, I investigate how democratic ideals have been negotiated in material forms, and what kind of audiences/visitors these spaces have conceptualized over time. Linking different kinds of sources, that speak from various levels and positions, has been an analytically important method.The analysis describes the museum as a meaning producing network that materially embody different, and sometimes conflicting ideologies. The public spaces have been shaped by tensions; between education versus pleasure, collecting versus showing, and by the dichotomy between culture and commerce. What is communicated thorough various materialities and inscriptions in the shop, the entrance, and the spaces for children sometimes contradict perspectives produced in exhibitions and educational programmes. Hierarchies between professional positions and knowledges propagate as social extensions towards the visitors, and sometimes, reproduce structural hierarchies. Museum functions literally “takes place”, depending on how they are valued and assigned meaning. The museum has increasingly included children, while also becoming a space for commerce. Various, and sometimes incompatible ideals on equality and inclusion have been implemented, simultaneously. At the same time, the public spaces carry unique spatial qualities, which can benefit inclusion. Concluding, the dissertation stresses that the entrance, the shop, the children spaces and other public spaces perceived as “peripheral” need to be viewed as central, not as superficial services or add-ons to the “real” museum experience, i.e. the exhibition.
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