| 1. |
- Timmen, Ludger, et al.
(författare)
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Observing Fennoscandian Gravity Change by Absolute Gravimetry
- 2006
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Ingår i: International Association of Geodesy Symposia, Vol. 131, Geodetic Deformation Monitoring: From Geophysical to Engineering Roles. ; , s. 193-199
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The Nordic countries Norway, Sweden, Denmark and Finland are a key study region for the research of glacial isostasy, and, in addition, it offers a unique opportunity for validating and testing the results of the GRACE experiment. Over a period of five years, the expected life time of GRACE, a temporal geoid variation of 3.0 mm is expected in the centre of the Fennoscandian land uplift area, corresponding to a gravity change of about 100 nm/s2. This is expected to be within the detection capabilities of GRACE. With terrestrial absolute gravimetry, the gravity change due to the land uplift can be observed with an accuracy of ±10 to 20 nm/s2 for a 5-year period. Thus, the terrestrial insitu observations (ground-truth) may be used to validate and test the GRACE results.Since 2003, absolute gravity measurements have been performed in Fennoscandia at about 30 stations covering Norway, Sweden, Finland and Denmark. Four groups with FG5 absolute gravimeters (BKG, FGI, IfE, UMB) are engaged to survey the uplift network annually by a mutually controlled procedure. Nearly all absolute stations are colocated with permanent GPS stations. From the 2003 and 2004 comparisons between the instruments, an overall accuracy of ±30 nm/s2 is indicated for a single absolute gravimeter and a single station determination. This is in full agreement with the project goal.
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| 2. |
- Ericsson, Olle, et al.
(författare)
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Clinical validation of a novel automated cell-free DNA screening assay for trisomies 21, 13, and 18 in maternal plasma.
- 2019
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Ingår i: Prenatal diagnosis. - : Wiley. - 1097-0223 .- 0197-3851. ; 39:11, s. 1011-1015
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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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| 3. |
- Alm, Björn
(författare)
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The un/selfish leader : Changing notions in a Tamil Nadu village
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 'The un/selfish' leader explores notions of selfishness, as they were perceived by people in the village of Ekkaraiyur, Tamil Nadu, India, at a time they associated with thorough changes in their lives.Discussing locally held notions about agrarian change, seen as causing the erosion of earlier village loyalties and leading to the emergence of a new type of leaders, the study focus on the censure of the alleged corruption of these leaders. Expressed in a rich repertoire of stories about the ideals of leadership and about the excellence of the past and foreign societies, the censure was routinely voiced in public debates and in everyday conversations.Set against a background an increasing role of the state for the people in Ekkaraiyur, the censure of leaders implied a critique of the contemporary society they were taken to represent. Moreover, the study argues that the critique was grounded in evaluations of individualism and selfishness in human nature.The study is based on fieldwork carried out in Ekkaraiyur between 1988 and 1990
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| 4. |
- Andersson, Björn, 1978-, et al.
(författare)
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Skolbränder och skolbrandsprevention : Underlag för planerade insatser enligt ”Karlstadsmodellen”
- 2009
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Kan man förebygga anlagda bränder och annan skadegörelse i skolor med miljöinriktade åtgärder? Den bedömningen gör man i Karlstads kommun med stöd i kriminologisk teori och erfarenheter från andra sektorer. Den traditionella ansatsen är annars är att kombinera brandtekniska åtgärder med ett mer individorienterat perspektiv riktat mot gärningspersoner. Syftet med föreliggande rapport är att ge en djupare belysning av den teoretiska grundvalen för en bredare miljöinriktad strategi, samt att peka på möjligheter att följa och utvärdera effekter av en lokal tillämpning. I bilaga redovisas även en forskningsöversikt kring den vetenskapliga evidens som idag föreligger beträffande miljöinriktad brottsprevention.
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| 5. |
- Blanck, Hans, 1950, et al.
(författare)
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A retrospective analysis of contamination and periphyton PICT patterns for the antifoulant irgarol 1051, around a small marina on the Swedish west coast
- 2009
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Ingår i: Marine Pollution Bulletin. - : Elsevier BV. - 0025-326X .- 1879-3363. ; 58:2, s. 230-237
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Tidskriftsartikel (refereegranskat)abstract
- Irgarol is a triazine photosystem II (PSII) inhibitor that has been used in Sweden as an antifouling ingredient since the 1990´s. Early microcosm studies indicated that periphyton was sensitive to irgarol at concentrations regularly found in harbours and marinas. However, field studies of irgarol effects on the Swedish west coast in 1994, using the Pollution-Induced Community Tolerance (PICT) approach, failed to detect any effects of the toxicant in the field. A PICT study involves sampling of replicate communities in a gradient of contamination, and a comparison of their community tolerance levels, with an increase being an indication that sensitive species have been eliminated and replaced by more tolerant ones. Typically, short-term assays are used to quantify the community tolerance levels. Later PICT studies in the same area over a 10 year period demonstrate that irgarol tolerance levels have increased, although the contamination pattern has been stable. Our results support the hypothesis that that the PICT potential was low initially, due to a small differential sensitivity between the community members, and that a persistent selection pressure was required to favour and enrich irgarol tolerant species or genotypes.
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| 6. |
- Carlsson, Björn, et al.
(författare)
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Enantioselective Analysis of Citalopram and Metabolites in Adolescents
- 2001
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Ingår i: Therapeutic drug monitoring. - : Ovid Technologies (Wolters Kluwer Health). - 0163-4356. ; 23, s. 658-
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Tidskriftsartikel (refereegranskat)abstract
- Studies of the antidepressant effect and pharmacokinetics of citalopram have been performed in adults, but the effects on children and adolescents have only been studied to a minor extent despite its increasing use in these age groups. The aim of this study was to investigate a group of adolescents treated for depression, with respect to the steady-state plasma concentrations of the enantiomers of citalopram and its demethylated metabolites desmethylcitalopram and didesmethylcitalopram. Moreover, the authors studied the genotypes for the polymorphic cytochrome P450 enzymes CYP2D6 and CYP2C19 in relation to the different enantiomers. The S/R ratios of citalopram and desmethylcitalopram found in this study of 19 adolescents were similar to studies involving older patients. The concentrations of the R-(-)- and S-(+)-enantiomers of citalopram and desmethylcitalopram were also in agreement with values from earlier studies, the R-(-)-enantiomer (distomer) being the major enantiomer. The results indicate that the use of oral contraceptives may have some influence on the metabolism of citalopram. This might be because of an interaction of the contraceptive hormones with the CYP2C19 enzyme.
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| 7. |
- Carlsson, Magnus, et al.
(författare)
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The Effect of Schooling on Cognitive Skills
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- How schooling affects cognitive skills is a fundamental question forstudies of human capital and labor markets. While scores on cognitive ability testsare positively associated with schooling, it has proven difficult to ascertain whetherthis relationship is causal. Moreover, the effect of schooling is difficult to separate from the confounding factors of age at test date, relative age within a classroom, season of birth, and cohort effects. In this paper, we use a fundamentally different identification approach compared to the previous literature. We exploit conditionally random variation in the assigned test date for a battery of cognitive tests which almost all 18 year-old males were required to take in preparation for military servicein Sweden. Both age at test date and number of days spent in school vary randomly across individuals after flexibly controlling for date of birth, parish, and expected graduation date (the three variables the military conditioned on when assigningtest date). We find an extra 10 days of school instruction raises cognitive scoreson crystallized intelligence tests (synonym and technical comprehension tests) by approximately one percent of a standard deviation, whereas extra nonschool dayshave almost no effect. The benefit of additional school days is homogeneous, with similar effect sizes based on past grades in school, parental education, and father’s earnings. In contrast, test scores on fluid intelligence tests (spatial and logic tests) do not increase with additional days of schooling, but do increase modestly with age. We discuss the importance of these findings for questions about the malleability of cognitive skills in young adults, schooling models of signaling versus human capital ,the interpretation of test scores in wage regressions, and policies related to the length of the school year
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| 8. |
- Carlsson, Magnus, 1975-, et al.
(författare)
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The Effect of Schooling on Cognitive Skills
- 2015
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Ingår i: Review of Economics and Statistics. - 0034-6535 .- 1530-9142. ; 97:3, s. 533-547
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Tidskriftsartikel (refereegranskat)abstract
- To identify the causal effect of schooling on cognitive skills, we exploit conditionally random variation in the date Swedish males take a battery of cognitive tests in preparation for military service. We find an extra 10 days of school instruction raises scores on crystallized intelligence tests (synonym and technical comprehension tests) by approximately one percent of a standard deviation, whereas extra nonschool days have almost no effect. In contrast, test scores on fluid intelligence tests (spatial and logic tests) do not increase with additional days of schooling, but do increase modestly with age.
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| 9. |
- Dahl, Alva, 1985-
(författare)
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I skriftens gränstrakter : Interpunktionens funktioner i tre samtida svenska romaner
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Punctuation is an indispensable element in formal and literary texts as well as everyday writing. Studying punctuation is therefore necessary in order to understand written language. Still, it does not fit easily into descriptions of language as an abstract, given system, composed of lexicon and grammar. Within the framework of Bakhtinian dialogism, however, linguists have started to study languaging as an interactive, situated process, meaningful in concrete, embodied utterances. While many such studies have focused on spoken language, this PhD dissertation is an attempt to study written language from a dialogical perspective. The aim of the study is to explore the functions of punctuation and to integrate the analysis of punctuation into a broader theoretical understanding of written language. This is achieved through qualitative analyses of three contemporary Swedish novels: DIVA by Monika Fagerholm (1998), Förvandling by Eva Adolfsson (2005) and Fadevår, tack för ljuset! by Fredrik Ekelund (2010). In order to discover the rich meaning of specific instances, linguistic details are studied in relation to different aspects of context: the local co-text of the sentence, paragraph, chapter and novel as a whole, relevant intertextual contexts, and, to some extent, contemporary literary movements and technological developments, etc.In all of the three novels, punctuation is an integrated element of style and characterization, and important thematic aspects of each novel are visible at the level of punctuation. General patterns are also to be seen, the most important of which concern, firstly, how punctuation divides the units of written language, and regulates the relationship between these units, and secondly, how shifts in voice and tone are constructed in the novels with the help of punctuation. Furthermore, punctuation can create visually iconic references. The results have many implications for further research. Punctuation is a necessary and integrated part of written meaning-making and should not be overlooked in text analyses. Moreover, punctuation plays a crucial role in the construction of aspects like viewpoint and discourse presentation, which can no longer be ignored. On the spatial surface of text, writers and readers create complex interplays of voices.
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| 10. |
- Dahl, Solveig, et al.
(författare)
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Sex differences in risk factors, treatment, and prognosis in acute stroke.
- 2020
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Ingår i: Women's health (London, England). - : SAGE Publications. - 1745-5065. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Stroke is a major cause of long-term disability and death worldwide. Several studies have shown that women in general have more severe symptoms at arrival to hospital and are less likely to return home and independent living. Our aim with the present study was to update previous results concerning sex differences in baseline characteristics, stroke management, and outcome in a population study from Sahlgrenska University Hospital, Gothenburg, Sweden.This study included patients with acute ischemic and hemorrhagic stroke in 2014 at Sahlgrenska University Hospital. All data were collected from The Swedish National Stroke Registry (Riksstroke).The study population consisted of 1453 patients, with 46.7% females. Women were 5years older than men. There was no sex difference in acute stroke severity. Frequency of revascularization was equal between men and women. The stroke mortality rate was the same between the sexes. At 3-months follow-up, women had a worse functional outcome and a higher frequency of depression and post-stroke fatigue.Our results show that there are no sex differences in management of acute stroke. However, the cause of worse functional outcome in women at 3-months follow-up, independent of other risk factors, is not clear and warrants further investigations.
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| 11. |
- Draptchinskaia, Natalia, et al.
(författare)
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The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia
- 1999
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 21:2, s. 169-75
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Tidskriftsartikel (refereegranskat)abstract
- Diamond-Blackfan anaemia (DBA) is a constitutional erythroblastopenia characterized by absent or decreased erythroid precursors. The disease, previously mapped to human chromosome 19q13, is frequently associated with a variety of malformations. To identify the gene involved in DBA, we cloned the chromosome 19q13 breakpoint in a patient with a reciprocal X;19 chromosome translocation. The breakpoint occurred in the gene encoding ribosomal protein S19. Furthermore, we identified mutations in RPS19 in 10 of 40 unrelated DBA patients, including nonsense, frameshift, splice site and missense mutations, as well as two intragenic deletions. These mutations are associated with clinical features that suggest a function for RPS19 in erythropoiesis and embryogenesis.
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- Flygt, Hjalmar, et al.
(författare)
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Long-term tolerability and efficacy after initial PegIFN-α addition to dasatinib in CML-CP : Five-year follow-up of the NordCML007 study
- 2021
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Ingår i: European Journal of Haematology. - : John Wiley & Sons. - 0902-4441 .- 1600-0609. ; 107:6, s. 617-623
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTreatment-free remission (TFR) has emerged as a treatment goal in chronic myeloid leukemia in the chronic phase (CML-CP). Attempts to increase proportion of patients achieving TFR include combination of tyrosine kinase inhibitors (TKI) and other drugs. Interferon-α in addition to TKI has shown promising efficacy but with dose-dependent toxicity and discontinuations. NordCML007 was initiated to study the efficacy and safety of low dose pegylated IFN-α (PegIFN-α) in combination with dasatinib (DAS) in CML-CP.MethodsForty patients with newly diagnosed CML-CP were given DAS upfront. After month 3 (M3) 15 μg/wk of PegIFN-α was added and increased to 25 μg/wk from M7 until M15. DAS treatment was continued and adverse events and BCR-ABL1 qRT-PCR values were reported yearly after M24. Results from M1 to M18 have previously been published, and here we present long-term data.ResultsAfter 5 years of follow-up, there were no suspected unexpected serious adverse reactions, no increase in serosal effusions, no disease progressions and no CML-related deaths. Rates of MR3.0 (MMR), MR4.0 and MR4.5 were 84.6%, 64.1% and 51.3% respectively at M60, and 95% of patients reached MMR at some point during the study.ConclusionInitial addition of PegIFN-α to DAS shows good long-term efficacy without increased toxicity.
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| 16. |
- Flygt, Hjalmar, et al.
(författare)
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Treatment-free remission after a second TKI discontinuation attempt in patients with Chronic Myeloid Leukemia re-treated with dasatinib - interim results from the DAstop2 trial.
- 2024
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Ingår i: Leukemia. - : Springer. - 0887-6924 .- 1476-5551.
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Tidskriftsartikel (refereegranskat)abstract
- Tyrosine kinase inhibitor (TKI) discontinuation in chronic myeloid leukemia (CML) has become part of routine care for patients with a sustained deep molecular response (DMR). Approximately 50% experience a molecular relapse upon TKI cessation. Most of them quickly regain DMR upon TKI resumption. Whether these patients can achieve a second treatment-free remission (TFR) remains unclear. DAstop2 (ClinicalTrials.gov ID: NCT03573596) is a prospective study including patients with a failed first TFR attempt re-treated with any TKI for ≥ one year. Upon entering the study, patients received the TKI dasatinib for additional two years. Patients with sustained DMR for ≥1 year qualified for a second TKI stop. Ninety-four patients were included between Oct 2017-Dec 2021. At the time of data analysis, 62 patients had attempted a 2nd stop. After a median follow-up of 27 months from 2nd stop, TFR rates were 61, 56 and 46% at 6, 12 and 24 months respectively. No progression to advanced stage disease was seen and 87% had re-achieved MR4 within a median of 3 months from TKI re-initiation. In summary, we show that a 2nd TFR attempt after dasatinib treatment is safe, feasible and TFR rates seem in the range of those reported in trials of a first TKI stop.
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| 17. |
- Fransson, Torbjörn, et al.
(författare)
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Nationwide Study of the Outcome of Treatment of Lower Extremity Atherosclerotic Lesions With Endovascular Surgery With or Without Drug Eluting Methods in Patients With Diabetes
-
Ingår i: Journal of Endovascular Therapy. - 1526-6028.
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Tidskriftsartikel (refereegranskat)abstract
- Paclitaxel eluting balloons and stents reduce the development of intimal hyperplasia and restenosis rate after endovascular treatment for peripheral arterial disease (PAD) in the lower extremities. As diabetes mellitus (DM) worsens the prognosis in PAD patients after invasive endovascular treatment, we assessed the effects of drug eluting technology for PAD with special focus on effects in patients with and without DM. All Swedish patients registered in the Swedish vascular registry Swedvasc after vascular or endovascular surgery for intermittent claudication, IC; (n=1948) or chronic limb threatening ischemia, CLTI (n=3353) in 2013 to 2015 were followed up regarding a composite of either major amputation and/or mortality during median 607 days and for reinterventions for PAD during median 522 days. Patients with DM registered in the Swedish National Diabetes Registry (NDR) and patients without DM were evaluated separately. The 201 CLTI patients with DM treated with drug eluting methods had a lower adjusted risk for amputation or mortality after adjustment than the 1476 CLTI patients with DM treated without drug eluting methods (hazard ratio [HR] 0.712 [0.562-0.901], P=.005). There were no differences among IC patients. Regarding the need for reinterventions for PAD, there were no differences between patients treated with and without drug eluting methods, irrespectively of the presence or absence of DM. In conclusion, this nationwide follow-up study indicated potential benefits of drug eluting treatment in CLTI patients with diabetes. The results need to be evaluated and confirmed in prospective randomized studies. Clinical Impact: This retrospective observational registry trial combines national registries for vascular surgical procedures and diabetes mellitus to clarify results of drug eluting technology in treating diabetic subjects with intermittent claudication or chronic limb threatening ischemia compared to treatment of non-diabetic subjects. As earlier proposed and showed in this trial, there may be an implication for a beneficial treatment efficacy with drug eluting therapy in the diabetic population with PAD compared to the non-diabetic population. A finding worth further exploration.
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| 18. |
- Gee, Kira, et al.
(författare)
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Can tools contribute to integration in MSP? : A comparative review of selected tools and approaches
- 2019
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Ingår i: Ocean and Coastal Management. - : Elsevier. - 0964-5691 .- 1873-524X. ; 179, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- The role of tools and approaches is currently much debated in maritime spatial planning (MSP). Past evaluation has mainly concentrated on decision support tools and the tangible outputs these can provide for MSP, but little attention has so far been been given to the soft or indirect benefits tool use can have in MSP. This paper assesses the potential benefits of tool use in the context of four common integration challenges in MSP. Drawing on case study material from the Baltic Sea region, the paper reviews the potential contribution of five selected tools and approaches to multi-level and transboundary, policy and sector, stakeholder and knowledge integration. Specific end points are defined for each integration challenge, including general desired outcomes of integrated MSP processes as a template for assessment. Our review shows that the selected tools play different roles in moving towards the various end points of MSP integration. There is an important difference between the potential of each tool, or its inherent capacity, and how it is applied, e.g. in a participative or non-participative setting. Another lesson is that some integration benefits can be achieved by the tools alone, while others – often secondary benefits - depend on how the outcomes of tool use are taken up by the subsequent MSP process. Although the nature of a tool does restrict its potential contribution to MSP integration challenges, the secondary “soft” benefits that can be achieved through certain styles of application and good links to the MSP process can add important integration benefits up and beyond the tool itself. The results presented here may also be relevant to other types of spatial planning and conservation management.
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| 19. |
- Grillitsch, Markus, et al.
(författare)
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Agency and economic change in regions : identifying routes to new path development using qualitative comparative analysis
- 2023
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Ingår i: Regional Studies. - : Informa UK Limited. - 0034-3404 .- 1360-0591. ; 57:8, s. 453-1468
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Tidskriftsartikel (refereegranskat)abstract
- This paper investigates the role of human agency in 40 phases of regional economic development in 12 Nordic regions over 30 years. It contributes with a theoretical framework to study agency over time and a fuzzy-set qualitative comparative analysis based on a unique dataset combining over 200 interviews, with printed and online sources, and quantitative data. The paper identifies which combinations of agency types and context conditions make industrial upgrading or diversification possible, and investigates how such combinations come into being. The causal claims from this analysis are illustrated with empirical examples and discussed in relation to previous literature.
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| 20. |
- Hassellöv, Ida-Maja, 1974, et al.
(författare)
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Verification of a benthic boxcosm system with potential for extrapolating experimental results to the field
- 2007
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Ingår i: Journal of Experimental Marine Biology and Ecology. - : Elsevier BV. - 0022-0981. ; 353:2, s. 265-278
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Tidskriftsartikel (refereegranskat)abstract
- A marine mesocosm system (boxcosm system) was developed for ecological and/or ecotoxicological studies of sediment community function and structure. The system consists of continuous flow-through incubations of intact sediment samples, each with a surface area of 0.25 m2. The experimental setup enables repeated non-destructive measurements of benthic fluxes, such as of nutrients, oxygen and dissolved inorganic carbon, over the sediment–water interface. The benthic fluxes reflect the function of the sediment community, integrating over the chemical, biological and physical activities in the sediment. The suitability of the boxcosm system for controlled, highly ecologically relevant studies of intact sediment communities was evaluated in two experiments of six weeks and five months duration respectively, where the functional and structural development over time was compared to the development of the sampling site. The function of the sediment was measured as nutrient and oxygen fluxes, and the structural component consisted of microbial functional diversity and meio- and macrofauna composition. Differences between the boxcosm and the sampling site were detected especially in nitrate fluxes and meiofauna diversity and abundance, but all differences fell within seasonal and inter-annual variability at the sampling site. The cause of the differences could be referred to differences in oxygen availability, supply of organic matter particles, and recruitment of larvae. These factors can however be compensated for within the present setup. The study shows that the boxcosms are suitable tools for ecologically relevant studies generating comparable conditions to the natural environment.
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| 21. |
- Holmgren, Per, et al.
(författare)
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Enantioselective analysis of citalopram and its metabolites in postmortem blood and genotyping for CYD2D6 and CYP2C19
- 2004
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Ingår i: Journal of Analytical Toxicology. - : Oxford University Press (OUP). - 0146-4760 .- 1945-2403. ; 28:2, s. 94-104
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Tidskriftsartikel (refereegranskat)abstract
- Citalopram, a selective serotonin reuptake inhibitor, is one of the most commonly found drugs in Swedish forensic autopsy cases. Citalopram is a racemic drug with 50:50 of the S- and R- enantiomers. Enantioselective analysis of citalopram and its metabolites desmethylcitalopram and didesmethylcitalopram were performed in femoral blood from 53 autopsy cases by a chiral high-performance liquid chromatography (HPLC) method. The mean (± standard deviation) S/R ratio for citalopram was 0.67 ± 0.25 and for desmethylcitalopram, 0.68 ± 0.20. We found increasing S/R ratios with increasing concentrations of citalopram. We also found that high citalopram S/R ratios were associated with a high parent drug-to-metabolite ratio and may be an indicator of recent intake. Citalopram is metabolized by cytochrome P450 (CYP) 3A4, 2C19, and 2D6. Genotyping for the polymorphic CYP2C19 and CYP2D6 revealed no poor metabolizers regarding CYP2C19 and only 2 (3.8%) poor metabolizers regarding CYP2D6. The presence of drugs metabolized by and/or inhibiting these enzymes in several of the cases suggests that such pharmacokinetic interactions are a more important (practical) problem than metabolic deficiency. Enantioselective analysis of citalopram and its metabolites can provide additional information when interpreting forensic toxicology results and might be a necessity in the future.
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| 22. |
- Huuhtanen, Jani, et al.
(författare)
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IFN-alfa with dasatinib broadens the immune repertoire in patients with chronic-phase chronic myeloid leukemia
- 2022
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Ingår i: Journal of Clinical Investigation. - : AMER SOC CLINICAL INVESTIGATION INC. - 0021-9738 .- 1558-8238. ; 132:17
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Tidskriftsartikel (refereegranskat)abstract
- In chronic myeloid leukemia (CML), combination therapies with tyrosine kinase inhibitors (TKIs) aim to improve the achievement of deep molecular remission that would allow therapy discontinuation. IFN-alpha is one promising candidate, as it has long-lasting effects on both malignant and immune cells. In connection with a multicenter clinical trial combining dasatinib with IFN-alpha in 40 patients with chronic-phase CML (NordCML007, NCT01725204), we performed immune monitoring with single-cell RNA and T cell receptor (TCR) sequencing (n = 4, 12 samples), bulk TCR beta sequencing (n = 13, 26 samples), flow cytometry (n = 40, 106 samples), cytokine analyses (n = 17, 80 samples), and ex vivo functional studies (n = 39, 80 samples). Dasatinib drove the immune repertoire toward terminally differentiated NK and CD8+ T cells with dampened functional capabilities. Patients with dasatinib-associated pleural effusions had increased numbers of CD8(+) recently activated effector memory T (Temra) cells. In vitro, dasatinib prevented CD3-induced cell death by blocking TCR signaling. The addition of IFN-alpha reversed the terminally differentiated phenotypes and increased the number of costimulatory intercellular interactions and the number of unique putative epitope-specific TCR clusters. In vitro IFN-alpha had costimulatory effects on TCR signaling. Our work supports the combination of IFN-alpha with TKI therapy, as IFN-alpha broadens the immune repertoire and restores immunological function.
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| 23. |
- Högberg, Björn, 1988-
(författare)
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Vulnerability and inequalities in health and wellbeing : the role of social policy
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis is to investigate the moderating role of social policies for the association between vulnerable social positions and health and wellbeing. Vulnerable social positions are identified in relation to age-related transition points in to or out of the labour market. Specifically, the focal groups are young adults, on the route to establish themselves in the labour market, and older persons, having just left the labour market, and inequalities by labour market status, class, or gender within these age groups. The thesis moreover aims to contribute to the theoretical development of the comparative health literature, by developing and implementing a theoretical framework for analyzing the role of social policy for the health and wellbeing of vulnerable groups.Data and methods: The aim is addressed through a cross-country comparative approach, by fitting multilevel regression models on harmonized individual level data from the European Social Survey. Specifically, cross-level interactions between social position and social policies are estimated, with self-reported general health and psychological wellbeing as outcomes. The focal social policies are pension systems and elderly care policies, as well as education policies.Results and conclusions: Overall, the empirical results showed that public investment in, and public organization of, elderly care was associated with smaller health inequalities by both social class and gender, and that redistributive minimum pensions were associated with smaller inequalities by social class, while more status-maintaining standard pensions were associated with larger gender-based inequalities. Regarding the role of education policies, the analyses showed that inclusive policies – specifically low degree of tracking, generous second chance opportunities, low out-of-pocket costs for, and a larger supply of, education – were associated with smaller inequalities by both social background and employment status. The overall conclusion of the thesis is that redistributive social policies, which distribute essential resources to vulnerable groups, have the potential to reduce inequalities in health and wellbeing between vulnerable and more advantaged groups.
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| 24. |
- Krackhardt, F., et al.
(författare)
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Results from the "Me & My Heart" (eMocial) Study: a Randomized Evaluation of a New Smartphone-Based Support Tool to Increase Therapy Adherence of Patients with Acute Coronary Syndrome
- 2023
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Ingår i: Cardiovascular Drugs and Therapy. - : Springer Science and Business Media LLC. - 0920-3206 .- 1573-7241. ; 37:4, s. 729-741
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose This study evaluated whether patient support, administered via an electronic device-based app, increased adherence to treatment and lifestyle changes in patients with acute coronary syndrome (ACS) treated with ticagrelor in routine clinical practice. Methods Patients (aged >= 18 years) with diagnosed ACS treated with ticagrelor co-administered with low-dose acetylsalicylic acid were randomized into an active group (with support tool app for medication intake reminders and motivational messages) and a control group (without support tool app), and observed for 48 weeks (ClinicalTrials.gov Identifier: NCT02615704). Patients were asked to complete the 36-item Short-Form Health Survey (SF-36) and Lifestyle Changes Questionnaire (LSQ), and were assessed for blood pressure and body mass index (BMI) at baseline (visit 1) and at the end of the study (visit 2). Medication adherence was measured using the Brilique Adherence Questionnaire (BAQ). Results Patients (N = 676) were randomized to an active (n = 342) or a control (n = 334) group. BAQ data were available for 174 patients in the active group and 174 patients in the control group. Over the 48-week period, mean (standard deviation) adherence for the active and control groups was 96.4% (13.2%) and 91.5% (23.1%), respectively (effect of app intervention, p < 0.05). There were no significant differences in blood pressure and BMI between visits. General improvements in SF-36 and LSQ scores were observed for both groups. Conclusion The patient support tool app was associated with significant improvements in patient-reported treatment adherence compared with a data collection app alone in patients prescribed ticagrelor for ACS.
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| 25. |
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| 26. |
- Krogvold, Lars, et al.
(författare)
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Detection of a low-grade enteroviral infection in the islets of Langerhans of living patients newly diagnosed with type 1 diabetes
- 2015
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 64:5, s. 1682-1687
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Tidskriftsartikel (refereegranskat)abstract
- The Diabetes Virus Detection study (DiViD) is the first to examine fresh pancreatic tissue at the diagnosis of type 1 diabetes for the presence of viruses. Minimal pancreatic tail resection was performed 3-9 weeks after onset of type 1 diabetes in 6 adult patients (age 24-35 years). The presence of enteroviral capsid protein 1 (VP1) and the expression of class I HLA were investigated by immunohistochemistry. Enterovirus RNA was analyzed from isolated pancreatic islets and from fresh frozen whole pancreatic tissue using PCR and sequencing. Non-diabetic organ donors served as controls. VP1 was detected in the islets of all type 1 diabetes patients (2 of 9 controls). Hyperexpression of class I HLA molecules was found in the islets of all patients (1 of 9 controls). Enterovirus specific RNA sequences were detected in 4 of 6 cases (0 of 6 controls). The results were confirmed in different laboratories. Only 1.7 % of the islets contained VP1 positive cells and the amount of enterovirus RNA was low. The results provides evidence for the presence of enterovirus in pancreatic islets of type 1 diabetic patients, being consistent with the possibility that a low grade enteroviral infection in the pancreatic islets contribute to disease progression in humans.
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| 27. |
- Krogvold, Lars, et al.
(författare)
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Insulitis and characterisation of infiltrating T cells in surgical pancreatic tail resections from patients at onset of type 1 diabetes
- 2016
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 59:3, s. 492-501
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesisIt is thought that T cells play a major role in the immune-mediated destruction of beta cells in type 1 diabetes, causing inflammation of the islets of Langerhans (insulitis). The significance of insulitis at the onset of type 1 diabetes is debated, and the role of the T cells poorly understood.MethodsIn the Diabetes Virus Detection (DiViD) study, pancreatic tissue from six living patients with recent-onset type 1 diabetes was collected. The insulitis was characterised quantitatively by counting CD3+ T cells, and qualitatively by transcriptome analysis targeting 84 T and B lymphocyte genes of laser-captured microdissected islets. The findings were compared with gene expression in T cells collected from kidney biopsies from allografts with ongoing cellular rejection. Cytokine and chemokine release from isolated islets was characterised and compared with that from islets from non-diabetic organ donors.ResultsAll six patients fulfilled the criteria for insulitis (5–58% of the insulin-containing islets in the six patients had ≥ 15 T cells/islet). Of all the islets, 36% contained insulin, with several resembling completely normal islets. The majority (61–83%) of T cells were found as peri-insulitis rather than within the islet parenchyma. The expression pattern of T cell genes was found to be markedly different in islets compared with the rejected kidneys. The islet-infiltrating T cells showed only background levels of cytokine/chemokine release in vitro.Conclusions/interpretationInsulitis and a significant reserve reservoir for insulin production were present in all six cases of recent-onset type 1 diabetes. Furthermore, the expression patterns and levels of cytokines argue for a different role of the T cells in type 1 diabetes when compared with allograft rejection.
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| 28. |
- Kuric, Enida, et al.
(författare)
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Demonstration of Tissue Resident Memory CD8 T Cells in Insulitic Lesions in Adult Patients with Recent-Onset Type 1 Diabetes
- 2017
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 0002-9440 .- 1525-2191. ; 187:3, s. 581-588
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Tidskriftsartikel (refereegranskat)abstract
- Subtypes of CD8(+) T cells in insulitic lesions in biopsy specimens from six subjects with recent-onset type 1 diabetes (T1D) and six nondiabetic matched controls were analyzed using simultaneous multicolor immunofluorescence. Also, insulitic islets based on accumulation of CD3(+) T cells were microdissected with laser-capture microscopy, and gene transcripts associated with inflammation and autoimmunity were analyzed. We found a substantial proportion, 43%, of the CD8(+) T cells in the insulitic lesions to display a tissue resident memory T cell (TRM) (CD8(+)CD69(+)CD103(+)) phenotype in T1D subjects. Most TRM cells were located in the insulitic lesion in the endocrine-exocrine interface. TRM cells were also sporadically found in islets of control subjects. Moreover, gene expression analysis showed a lack of active transcription of genes associated with acute inflammatory or cytotoxic T-cell responses. We present evidence that a substantial proportion of T cells in insulitic lesions of recent-onset T1D patients are TRM cells and not classic cytotoxic CD8(+) T cells. Our findings highlight the need for further analysis of the T cells involved in insulitis to elucidate their role in the etiology of T1D.
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| 29. |
- Lindqvist, Karin, et al.
(författare)
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Affect-Focused Psychodynamic Internet-Based Therapy for Adolescent Depression : Randomized Controlled Trial
- 2020
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Ingår i: Journal of Medical Internet Research. - Toronto, ON, Canada : JMIR Publications Inc.. - 1438-8871. ; 22:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Adolescent depression is one of the largest health issues in the world and there is a pressing need for effective and accessible treatments.Objective: This trial examines whether affect-focused internet-based psychodynamic therapy (IPDT) with therapist support is more effective than an internet-based supportive control condition on reducing depression in adolescents.Methods: The trial included 76 adolescents (61/76, 80% female; mean age 16.6 years), self-referred via an open access website and fulfilling criteria for major depressive disorder. Adolescents were randomized to 8 weeks of IPDT (38/76, 50%) or supportive control (38/76, 50%). The primary outcome was self-reported depressive symptoms, measured with the Quick Inventory of Depressive Symptomatology for Adolescents (QIDS-A17-SR). Secondary outcomes were anxiety severity, emotion regulation, self-compassion, and an additional depression measure. Assessments were made at baseline, postassessment, and at 6 months follow-up, in addition to weekly assessments of the primary outcome measure as well as emotion regulation during treatment.Results: IPDT was significantly more effective than the control condition in reducing depression (d=0.82, P=.01), the result of which was corroborated by the second depression measure (d=0.80, P<.001). IPDT was also significantly more effective in reducing anxiety (d=0.78, P<.001) and increasing emotion regulation (d=0.97, P<.001) and self-compassion (d=0.65, P=.003). Significantly more patients in the IPDT group compared to the control group met criteria for response (56% vs 21%, respectively) and remission (35% vs 8%, respectively). Results on depression and anxiety symptoms were stable at 6 months follow-up. On average, participants completed 5.8 (SD 2.4) of the 8 modules.Conclusions: IPDT may be an effective intervention to reduce adolescent depression. Further research is needed, including comparisons with other treatments.Trial Registration: International Standard Randomised Controlled Trial Number (ISRCTN) 16206254; http://www.isrctn.com/ISRCTN16206254
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| 30. |
- Länne, T, et al.
(författare)
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Noninvasive measurement of diameter changes in the distal abdominal aorta in man
- 1992
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Ingår i: Ultrasound in Medicine and Biology. - 0301-5629. ; 18:5, s. 451-457
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Tidskriftsartikel (refereegranskat)abstract
- An ultrasound phase-locked, echo-tracking system was used to determine the dynamic properties of the distal abdominal aorta in 10 Caucasian male subjects (mean age, 25 years). Recordings were made at rest and during the blood pressure increase resulting from isometric exercise. The pressure diameter curve was nonlinear with an inflection at about 90-110 mmHg. Above this pressure range, the vessel was stiffer (less compliant), but the pressure diameter relationship was roughly linear above as well as below the inflection. Individual pressure diameter curves showed hysteresis, i.e., the aorta had a smaller diameter during expansion than during retraction at corresponding pressures. The pressure strain elastic modulus (Ep) and stiffness (beta) were at rest [Mean Arterial Pressure (MAP), 81 mmHg] 0.70 10(5) N/m2 and 6.0, respectively. During isometric exercise (MAP, 122 mmHg), Ep increased significantly by 91% and stiffness (beta) nonsignificantly by 27%. The variability of the compliance determinations was 5% when the ultrasonic system was combined with intra-arterial blood pressure measurements and less than 7% when combined with auscultatory blood pressure measurements. It is concluded that the phase-locked, echo-tracking system fulfills clinical requirements for routine measurements of vascular compliance.
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| 31. |
- Lööf, Birgitta, et al.
(författare)
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Krav på långsamhet efterlyses i byggdebatten
- 2019
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Annan publikation (populärvet., debatt m.m.)abstract
- Forcerade planprocesser är fel väg att gå om regeringsförklaringens uppmaning om snabbare och billigare bostadsbyggande ska bli verklighet. Det är inte reglerna som är krångliga – det är verkligheten. Stadsbyggnad måste få ta tid, skriver juryn för Sveriges Arkitekters Planpris.
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| 32. |
- Mechler, Jakob, et al.
(författare)
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Internet-based psychodynamic versus cognitive behaviour therapy for adolescents with depression : study protocol for a non-inferiority randomized controlled trial (the ERiCA study)
- 2020
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Adolescent depression is a common mental health problem and there is an urgent need for effective and accessible treatments. Internet-based interventions solve many obstacles for seeking and receiving treatment, thus increasing access to effective treatments. Internet-based cognitive behavioural therapy (ICBT) for adolescent depression has demonstrated efficacy in previous trials. In order to broaden the range of evidence-based treatments for young people, we evaluated a newly developed affect-focused Internet-based psychodynamic treatment (IPDT) in a previous study with promising results. The purpose of the planned study is to evaluate the efficacy of IPDT for adolescent depression in a non-inferiority trial, comparing it to ICBT.Methods: The study will employ a parallel randomized non-inferiority design (ratio 1:1; n = 270). Eligible participants are adolescents 15–19 years suffering from depression. The primary hypothesis is that IPDT will be non-inferior to ICBT in reducing depressive symptoms from pre-treatment to end of treatment. Secondary research questions include comparing outcomes of IPDT and ICBT regarding anxiety symptoms, emotion regulation and self-compassion. Additional data will be collected to evaluate cost-effectiveness as well as investigating predictors, moderators and mediators of outcome. In addition, we will examine long-term outcome up to 1 year after end of treatment. Diagnostic interviews with MINI 7.0 will be used to establish primary diagnosis of depression as well as ruling out any exclusion criteria. Both treatments consist of eight modules over 10 weeks, complemented with therapist support through text messages and weekly chat sessions. Primary outcome measure is the Quick Inventory of Depressive Symptomatology in Adolescents Self-Rated (QIDS-A17-SR). Primary outcome will be analysed using data from all participants entering the study using a multilevel growth curve strategy based on the weekly measurements of QIDS-A17-SR. The non-inferiority margin is defined as d = 0.30.Discussion: This trial will demonstrate whether IPDT is non-inferior to ICBT in the treatment of adolescent depression. The study might therefore broaden the range of evidence-based treatment alternatives for young people struggling with depression. Further analyses of data from this trial may increase our knowledge about “what works for whom” and the pathways of change for two distinct types of interventions.Trial registration: ISRCTN12552584, Registered on 13 August 2019.
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| 33. |
- Mechler, Jakob, et al.
(författare)
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Therapist-guided internet-based psychodynamic therapy versus cognitive behavioural therapy for adolescent depression in Sweden : a randomised, clinical, non-inferiority trial
- 2022
-
Ingår i: The Lancet Digital Health. - : Elsevier. - 2589-7500. ; 4:8, s. e594-e603
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Adolescent major depressive disorder (MDD) is highly prevalent and associated with lifelong adversity. Evidence-based treatments exist, but accessible treatment alternatives are needed. We aimed to compare internet-based psychodynamictherapy (IPDT) with an established evidence-based treatment (internet-based cognitive behavioural therapy [ICBT]) for the treatment of adolescents with depression.Methods: In this randomised, clinical trial, we tested whether IPDT was non-inferior to ICBT in the treatment of adolescent MDD. Eligible participants were 15–19 years old, presenting with a primary diagnosis of MDD according to DSM-5. Participants were recruited nationwide in Sweden through advertisements on social media, as well as contacts with junior and senior high schools, youth associations, social workers, and health-care providers. Adolescents who scored 9 or higher on the Quick Inventory of Depressive Symptomatology for Adolescents (QIDS-A17-SR) in an initial online screening were contacted by telephone for a diagnostic assessment using the Mini International Neuropsychiatric Interview. Participants were randomly assigned to ICBT or IPDT. Both interventions comprised eight self-help modules delivered over 10 weeks on a secure online platform. The primary outcome was change in depression severity measured weekly by the QIDS-A17-SR. Primary analyses were based on an intention-to-treat sample including all participants randomly assigned. A non-inferiority margin of Cohen's d=0·30 was predefined. The study is registered at ISRCTN, ISRCTN12552584.Findings: Between Aug 19, 2019, and Oct 7, 2020, 996 young people completed screening; 516 (52%) were contacted for a diagnostic interview. 272 participants were eligible and randomly assigned to ICBT (n=136) or IPDT (n=136). In the ICBT group, 51 (38%) of 136 participants were classified as remitted, and 54 (40%) of 136 participants were classified as remitted in the IPDT group. Within-group effects were large (ICBT: within-group d=1·75, 95% CI 1·49 to 2·01; IPDT: within-group d=1·93, 1·67 to 2·20; both p<0·0001). No statistically significant treatment difference was found in the intention-to-treat analysis. Non-inferiority for IPDT was shown for the estimated change in depression during treatment (d=–0·18, 90% CI –0·49 to 0·13; p=0·34). All secondary outcomes showed non-significant between-group differences.Interpretation: IPDT was non-inferior to ICBT in terms of change in depression for the treatment of adolescents with MDD. This finding increases the range of accessible and effective treatment alternatives for adolescents with depression.
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| 34. |
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| 35. |
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| 36. |
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| 37. |
- Reis, Margareta, 1959-, et al.
(författare)
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Serum levels of citalopram and its main metabolites in adolescent patients treated in a naturalistic clinical setting
- 2002
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Ingår i: Journal of Clinical Psychopharmacology. - : Ovid Technologies (Wolters Kluwer Health). - 0271-0749 .- 1533-712X. ; 22:4, s. 406-413
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Tidskriftsartikel (refereegranskat)abstract
- The prescribing of selective serotonin reuptake inhibitors for adolescents is extensive despite the fact that there are few pharmacokinetic (PK), effi]cacy, safety, or tolerability studies on this group. This study reports the PK findings from two trials in adolescents treated with citalopram (CIT) in naturalistic clinical settings: one retrospective and one prospective. The aim of our study was to describe serum concentrations of CIT, desmethylcitalopram (DCIT), and didesmethylcitalopram (DDCIT) (trough values in steady state) in adolescents in relation to daily dose and clinical information obtained from therapeutic drug monitoring request forms. Altogether, 44 patients younger than 21 years were scrutinized using this combined open-label approach. The main findings were that (1) there was a pronounced interindividual variability of serum CIT, DCIT, and DDCIT concentrations in all doses prescribed, in agreement with previous studies on adults; on correcting for dose, the coefficient of variance was about 50% for CIT, DCIT, and DDCIT; (2) the transformation of CIT to DCIT and of DCIT to DDCIT was similar within the dose range 20 to 60 mg/day; (3) there was a difference between the sexes on comparing the dose-corrected concentrations of CIT and DCIT, with girls presenting significantly higher values than boys; and (4) there was a strong dose-serum concentration relationship in three identified subgroups of adolescents: (a) nonsmokers (CIT, r 2 = 0.71; DCIT, r 2 = 0.81), (b) girls not taking oral contraceptives (CIT, r 2 = 0.75; DCIT, r 2 = 0.71,), and (c) girls in the last 14 days of the menstrual cycle (CIT, r 2 = 0.68; DCIT, r 2 = 0.64). In summary, the present study tentatively supports influences of sex, oral contraceptives, and smoking habits on the disposition of CIT in younger patients. Hence, future studies on CIT should assess these parameters.
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| 38. |
- Rogell, Björn, et al.
(författare)
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Adaptive divergence in body size overrides the effects of plasticity across natural habitats in the brown trout
- 2013
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 3:7, s. 1931-1941
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Tidskriftsartikel (refereegranskat)abstract
- The evolution of life-history traits is characterized by trade-offs between different selection pressures, as well as plasticity across environmental conditions. Yet, studies on local adaptation are often performed under artificial conditions, leaving two issues unexplored: (i) how consistent are laboratory inferred local adaptations under natural conditions and (ii) how much phenotypic variation is attributed to phenotypic plasticity and to adaptive evolution, respectively, across environmental conditions? We reared fish from six locally adapted (domesticated and wild) populations of anadromous brown trout (Salmo trutta) in one semi-natural and three natural streams and recorded a key life-history trait (body size at the end of first growth season). We found that population-specific reaction norms were close to parallel across different streams and Q(ST) was similar - and larger than F-ST - within all streams, indicating a consistency of local adaptation in body size across natural environments. The amount of variation explained by population origin exceeded the variation across stream environments, indicating that genetic effects derived from adaptive processes have a stronger effect on phenotypic variation than plasticity induced by environmental conditions. These results suggest that plasticity does not swamp the phenotypic variation, and that selection may thus be efficient in generating genetic change.
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| 39. |
- Rogell, Björn, et al.
(författare)
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Strong divergence in trait means but not in plasticity across hatchery and wild populations of sea-run brown trout Salmo trutta
- 2012
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Ingår i: Molecular Ecology. - 0962-1083 .- 1365-294X. ; 21:12, s. 2963-2976
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Tidskriftsartikel (refereegranskat)abstract
- There is ample evidence that organisms adapt to their native environment when gene flow is restricted. However, evolution of plastic responses across discrete environments is less well examined. We studied divergence in means and plasticity across wild and hatchery populations of sea-run brown trout (Salmo trutta) in a common garden experiment with two rearing environments (hatchery and a nearly natural experimental stream). Since natural and hatchery environments differ, this arrangement provides an experiment in contemporary adaptation across the two environments. A QST - FST approach was used to investigate local adaptation in survival and growth over the first summer. We found evidence for divergent selection in survival in 1 year and in body length in both years and rearing environments. In general, the hatchery populations had higher survival and larger body size in both environments. QST in body size did not differ between the rearing environments, and constitutive divergence in the means was in all cases stronger than divergence in the plastic responses. These results suggest that in this system, constitutive changes in mean trait values are more important for local adaptation than increased plasticity. In addition, ex situ rearing conditions induce changes in trait means that are adaptive in the hatchery, but potentially harmful in the wild, suggesting that hatchery rearing is likely to be a suboptimal management strategy for trout populations facing selection in the stream environment.
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| 40. |
- Saunders, Fred, 1961-, et al.
(författare)
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BONUS BALTSPACE Deliverable D2.4 : MSP as a governance approach? Knowledge integration challenges in MSP in the Baltic Sea
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Developing integrative decision-making underpinned by a diverse knowledge base is seen as essential to meet marine spatial planning’s (MSP) sustainable development aspirations. In contributing to a better understanding of how this might be achieved, this report considers knowledge integration challenges drawing on several MSP empirical cases across the Baltic Sea Region. Each case-study, involves Baltic Sea states at different stages of developing national marine spatial plans. At the Baltic-wide level, HELCOM-VASAB has interpreted the Ecosystem Approach in MSP as relying heavily on an evidence-base informed by natural scientific and expert knowledge. The results of the report show that challenges arise when trying to apply scientific knowledge to MSP events or processes for a number of reasons such as, incomplete data and associated substantial uncertainty or because stakeholders contest the policy interpretation of the data. This raises questions of how to assess or evaluate the quality and comprehensiveness/sufficiency of scientific and stakeholder knowledge or input into MSP decision-making, particularly in highly politicised, conflictual contexts, such as the integration of parts of the fishing sector in MSP in Poland. MSP in German territorial waters provides a positive example, where science and stakeholder knowledge input have been integrated in decision-making through informal and formal processes. This case exhibits evidence of social learning where authorities have reflected on previous experiences and invested in actively nurturing the meaningful participation of a wide variety of stakeholders (to form a community of practice) over an extended period of time. The key findings of the report call for more attention to be paid to ways that scientific and stakeholder knowledge can be fruitfully incorporated in MSP, through initiatives such as: the development of knowledge evaluation measures; drawing more actively on social science expertise to help facilitate processes of stakeholder engagement and knowledge inclusion; and paying more attention to how to include heterogeneous socio-cultural values and knowledge (placed-based) in a way that improves the salience of scientific knowledge and the legitimacy of MSP decision-making.
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| 41. |
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| 42. |
- Stattin, Eva-Lena, et al.
(författare)
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A missense mutation in the aggrecan C-type lectin domain disrupts extracellular matrix interactions and causes dominant familial osteochondritis dissecans
- 2010
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 86:2, s. 126-137
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Tidskriftsartikel (refereegranskat)abstract
- Osteochondritis dissecans is a disorder in which fragments of articular cartilage and subchondral bone dislodge from the joint surface. We analyzed a five-generation family in which affected members had autosomal-dominant familial osteochondritis dissecans. A genome-wide linkage analysis identified aggrecan (ACAN) as a prime candidate gene for the disorder. Sequence analysis of ACAN revealed heterozygosity for a missense mutation (c.6907G > A) in affected individuals, resulting in a p.V2303M amino acid substitution in the aggrecan G3 domain C-type lectin, which mediates interactions with other proteins in the cartilage extracellular matrix. Binding studies with recombinant mutated and wild-type G3 proteins showed loss of fibulin-1, fibulin-2, and tenascin-R interactions for the V2303M protein. Mass spectrometric analyses of aggrecan purified from patient cartilage verified that V2303M aggrecan is produced and present in the tissue. Our results provide a molecular mechanism for the etiology of familial osteochondritis dissecans and show the importance of the aggrecan C-type lectin interactions for cartilage function in vivo.
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| 43. |
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| 44. |
- Steneberg, Pär, et al.
(författare)
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PAN-AMPK activator O304 improves glucose homeostasis and microvascular perfusion in mice and type 2 diabetes patients
- 2018
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Ingår i: JCI INSIGHT. - : American Society for Clinical Investigation. - 2379-3708. ; 3:12
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Tidskriftsartikel (refereegranskat)abstract
- AMPK activated protein kinase (AMPK), a master regulator of energy homeostasis, is activated in response to an energy shortage imposed by physical activity and caloric restriction. We here report on the identification of PAN-AMPK activator O304, which - in diet-induced obese mice - increased glucose uptake in skeletal muscle, reduced beta cell stress, and promoted beta cell rest. Accordingly, O304 reduced fasting plasma glucose levels and homeostasis model assessment of insulin resistance (HOMA-IR) in a proof-of-concept phase IIa clinical trial in type 2 diabetes (T2D) patients on Metformin. T2D is associated with devastating micro-and macrovascular complications, and O304 improved peripheral microvascular perfusion and reduced blood pressure both in animals and T2D patients. Moreover, like exercise, O304 activated AMPK in the heart, increased cardiac glucose uptake, reduced cardiac glycogen levels, and improved left ventricular stroke volume in mice, but it did not increase heart weight in mice or rats. Thus, O304 exhibits a great potential as a novel drug to treat T2D and associated cardiovascular complications.
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| 45. |
- Teni, F. S., et al.
(författare)
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Variations in Patients' Overall Assessment of Their Health Across and Within Disease Groups Using the EQ-5D Questionnaire: Protocol for a Longitudinal Study in the Swedish National Quality Registers
- 2021
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Ingår i: Jmir Research Protocols. - Toronto, ON, Canada : JMIR Publications Inc.. - 1929-0748. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- Background: EQ-5D is one of the most commonly used questionnaires to measure health-related quality of life. It is included in many of the Swedish National Quality Registers (NQRs). EQ-5D health states are usually summarized using "values" obtained from members of the general public, a majority of whom are healthy. However, an alternative, which remains to be studied in detail, is the potential to use patients' self-reported overall health on the visual analog scale (VAS) as a means of capturing experience-based perspective. Objective: The aim of this study is to assess EQ VAS as a valuation method with an experience-based perspective through comparison of its performance across and within patient groups, and with that of the general population in Sweden. Methods: Data on nearly 700,000 patients from 12 NQRs covering a variety of diseases/conditions and nearly 50,000 individuals from the general population will be analyzed. The EQ-5D-3L data from the 12 registers and EQ-5D-5L data from 2 registers will be used in the analyses. Longitudinal studies of patient-reported outcomes among different patient groups will be conducted in the period from baseline to 1-year follow-up. Descriptive statistics and analyses comparing EQ-5D dimensions and observed self-assessed EQ VAS values across and within patient groups will be performed. Comparisons of the change in health state and observed EQ VAS values at 1-year follow-up will also be undertaken. Regression models will be used to assess whether EQ-5D dimensions predict observed EQ VAS values to investigate patient value sets in each patient group. These will be compared across the patient groups and with the existing Swedish experience-based VAS and time trade-off value sets obtained from the general population. Results: Data retrieval started in May 2019 and data of patients in the 12 NQRs and from the survey conducted among the general population have been retrieved. Data analysis is ongoing on the retrieved data. Conclusions: This research project will provide information on the differences across and within patient groups in terms of self-reported health status through EQ VAS and comparison with the general population. The findings of the study will contribute to the literature by exploring the potential of self-assessed EQ VAS values to develop value sets using an experience-based perspective.
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| 46. |
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