| 1. |
- Montagnese, Sara, et al.
(författare)
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A pilot study of golexanolone, a new GABA-A receptor-modulating steroid antagonist, in patients with covert hepatic encephalopathy
- 2021
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Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 75:1, s. 98-107
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Golexanolone is a novel small molecule GABA-A receptor-modulating steroid antagonist under development for the treatment of cognitive and vigilance disorders caused by allosteric over-activation of GABA-A receptors by neurosteroids. It restored spatial learning and motor coordination in animal models of hepatic encephalopathy (HE) and mitigated the effects of intravenous allopregnanolone in healthy adults in a dose-dependent fashion. Herein, we report data on the safety, pharmacokinetics (PK) and efficacy of golexanolone in adult patients with cirrhosis.Methods: Following single/multiple ascending dose studies, adults with Child-Pugh A/B cirrhosis and abnormal continuous reaction time (CRT) on screening were randomized to 3 weeks’ dosing with golexanolone (10, 40 or 80 mg BID) or placebo. CRT, psychometric hepatic encephalopathy score (PHES), animal naming test (ANT), Epworth sleepiness scale (ESS) and electroencephalogram (mean dominant frequency [MDF]; delta+theta/alpha+beta ratio [DT/AB]) were obtained at baseline, 10, and 21 days.Results: Golexanolone exhibited satisfactory safety and PK. Baseline characteristics were similar between the 12 and 33 patients randomized to placebo or golexanolone, respectively. By prespecified analyses, golexanolone was associated with directionally favourable changes vs. placebo in ESS (p = 0.047), MDF (p = 0.142) and DT/AB (p = 0.021). All patients also showed directionally favourable changes in CRT, PHES and ANT, but with no statistical difference between golexanolone and placebo. Post hoc analyses taking into account the variability and improvement in CRT, PHES and ANT observed between screening and baseline suggested an efficacy signal by cognitive measures as well.Conclusion: Golexanolone was well tolerated and associated with improvement in cognitive performance. These results implicate GABA-A receptor-modulating neurosteroids in the pathogenesis of HE and support the therapeutic potential of golexanolone.Lay summary: Many patients with cirrhosis experience subtle but disabling cognitive problems, including sleepiness and poor attention span, that impair their ability to be gainfully employed or carry out activities of daily living. This pilot study tested the hypothesis that these problems with cognition, for which there is no approved treatment, might be improved by an experimental drug, golexanolone, designed to normalize the function of receptors which inhibit brain function. The results of this study suggest that golexanolone is well tolerated and may improve cognition, as reflected by measures of sleepiness, attention span and brain wave activity, paving the way for future larger studies of this promising experimental drug.Clinical trial registration number: EudraCT 2016-003651-30.
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| 2. |
- Apel, Jan, 1965-, et al.
(författare)
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Fågelbacken och trattbägarsamhället : samhällsorganisation och rituella samlingsplatser vid övergången till en bofats tillvaro i östra Mellansverige
- 1995
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Ingår i: Tor. - Uppsala : Tor. - 0495-8772. ; 27, s. 47-132
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- A discussion of the TRB cultural landscape and form of society is attempted on the basis of the excavation of an Early Neolithic Funnel-beaker settlement site at Fågelbacken in eastern central Sweden. The site, situated on top of an esker, is characterized by finds of TRB pottery, quartz and flint debitage, pits with charred human bones, a cultbuilding and D-shaped huts. As a result of intra-site spatial analysis, ceramic analysis and a discussion of the site features, it is suggested that Fågelbacken should be interpreted not only as a coastal hunting site but also as a repeatedly visited, communal ritual site. A spatial analysis of thin-butted axes in the area surrounding the site, suggests that it is probably one of a whole series of similar, evenly spaced, ritual sites in the area. A sociocultural interpretation of Funnel-beaker huts and houses, together with an analysis of the distribution of stray finds of TRB type in the research area, further suggests that coastal sites like Fågelbacken are structurally related to groups of swidden-agriculture farmsteads and hunting stations in the interior.
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| 3. |
- Backström, Fredrik, et al.
(författare)
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Surgical Needs at the End of the Battle of Mosul: Results from Mosul General Hospital
- 2020
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Ingår i: World Journal of Surgery. - : SPRINGER. - 0364-2313 .- 1432-2323.
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The aim of the study was to analyze the surgical needs of patients seeking emergency care at the Mosul General Hospital in the final phase of the battle of Mosul in northern Iraq between an international military coalition and rebel forces. During the conflict, the International Red Committee of the Red Cross (ICRC) supported the hospital with staff and resources. Ceasefire in the conflict was declared at the end of July 2017. Methods Routinely collected hospital data from the ICRC-supported Mosul General Hospital from June 6, 2017, to October 1, 2017 were collected and analyzed retrospectively. All patients with weapon-related injuries as well as all patients with other types of injuries or acute surgical illness were included. Results Some 265 patients were admitted during the study period. Non-weapon-related conditions were more common than weapon-related (55.1%). The most common non-weapon-related condition was appendicitis followed by hernia and soft tissue wounds. Blast/fragment was the most frequent weapon-related injury mechanism followed by gunshot. The most commonly injured body regions were chest and abdomen. Children accounted for 35.3% of all weapon-related injuries. Patients presented at the hospital with weapon-related injuries more than 2 months after the official declaration of ceasefire. A majority of the non-weapon-related, as well as the weapon-related conditions, needed surgery (88.1% and 87.6%, respectively). Few postoperative complications were reported. Conclusions The number of children affected by the fighting seems to be higher in this cohort compared to previous reports. Even several months after the fighting officially ceased, patients with weapon-related injuries were presenting. Everyday illnesses or non-weapon-related injuries dominated. This finding underlines the importance of providing victims of conflicts with surgery for life-threatening conditions, whether weapon related or not.
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| 4. |
- Bengtsson, Martin, et al.
(författare)
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Experimental method for verification of calculated Cs-137 content in nuclear fuel assemblies
- 2022
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Ingår i: Nuclear Technology. - : Informa UK Limited. - 0029-5450 .- 1943-7471. ; 208:2, s. 295-302
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Tidskriftsartikel (refereegranskat)abstract
- A method to determine the absolute activity of 137Cs in irradiated nuclear fuel is presented. Using a well-known point-like calibration source in combination with measurements of the gamma-ray intensity from the nuclear fuel and Monte Carlo calculations based on the nominal measurement geometry, the activity content can be determined without prior knowledge of the intrinsic detection efficiency of the gamma-ray detector. The presented method is tested using measurements of the 137Cs intensity from spent nuclear fuel of the pressurized water type at the central interim storage in Sweden. Using an assumption of homogeneous distribution of 137Cs throughout the fuel, we demonstrate a linear relationship between measured activity and the activity calculated by a state-of-the-art simulation code. For future studies, we suggest some factors that potentially can decrease the uncertainty in the correlation between measured and calculated activity.
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| 5. |
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| 6. |
- Björklund, Fredrik, et al.
(författare)
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Company norms affect which traits are preferred in job candidates and may cause employment discrimination
- 2012
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Ingår i: The Journal of Psychology: Interdisciplinary and applied. - : Informa UK Limited. - 1940-1019. ; 146:6, s. 579-594
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated a possible mechanism behind employment discrimination. Participants completed a recruitment task where emphasis on cohesion (employees should “fit in”) vs. fairness (everybody should be treated equally) was manipulated by describing the norms of a fictitious company differently. There was a comparatively stronger preference in the cohesion condition for traits and interview questions related to social competence (e.g. friendliness, gregariousness, empathy). Furthermore, participants in the cohesion condition primarily pictured socially competent employees, whereas those in the fairness condition primarily pictured employees possessing productivity-related characteristics (e.g. education, experience and talent). The norm effect was moderated by participants’ awareness of the applicants’ ethnicity. When expecting applicants with foreign backgrounds, participants in the cohesion condition showed increased preference for selection methods related to social competence. Implications for recruitment practices are discussed.
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| 7. |
- Björklund, Fredrik, et al.
(författare)
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In-group ratings are affected by who asks and how: interactive effects of experimenter group-membership and response format.
- 2011
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Ingår i: Journal of Social Psychology. - : Informa UK Limited. - 0022-4545 .- 1940-1183. ; 151:5, s. 625-634
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Tidskriftsartikel (refereegranskat)abstract
- In three experiments, participants rated how well a number of adjectives described their in-group (e.g. kind-hearted, helpful, intelligent, efficient, etc.). In Experiment 1, females were found to rate their ingroup (females) more favorably when reporting verbally to female (rather than male) experimenters. This finding was further explored in two subsequent experiments where response format (written vs. verbal) was also manipulated. Both experiments revealed an interaction such that ethnic Swedes rated their in-group (Swedes) the most favorably when reporting verbally to an in-group experimenter and the least favorably when reporting verbally to a Middle Eastern experimenter. Results are discussed in relation to correction and contextual activation of social norms.
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| 8. |
- Björklund, Fredrik, et al.
(författare)
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Individual differences in processing styles: validity of the Rational-Experiential Inventory.
- 2008
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Ingår i: Scandinavian Journal of Psychology. - : Wiley. - 1467-9450 .- 0036-5564. ; 49:5, s. 439-446
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Tidskriftsartikel (refereegranskat)abstract
- In Study 1 (N= 203) the factor structure of a Swedish translation of Pacini and Epstein's Rational-Experiential Inventory (REI-40) was investigated using confirmatory factor analysis. The hypothesized model with rationality and experientiality as orthogonal factors had satisfactory fit to the data, significantly better than alternative models (with two correlated factors or a single factor). Inclusion of "ability" and "favorability" subscales for rationality and experientiality increased fit further. It was concluded that the structural validity of the REI is adequate. In Study 2 (N= 72) the REI-factors were shown to have theoretically meaningful correlations to other personality traits, indicating convergent and discriminant validity. Finally, scores on the rationality scale were negatively related to risky choice framing effects in Kahneman and Tversky's Asian disease task, indicating concurrent validity. On the basis of these findings it was concluded that the test has satisfactory psychometric properties.
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| 9. |
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| 10. |
- Bäckström, Fredrik, 1971, et al.
(författare)
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Absence of in vitro responses to type II collagen by splenocytes from arthritic BALB/c mice is possibly caused by intrinsic CD25+ regulatory cells.
- 2008
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Ingår i: Scandinavian journal of immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 67:4, s. 362-9
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Tidskriftsartikel (refereegranskat)abstract
- Collagen-induced arthritis-resistant BALB/c mice develop arthritis if a foreign protein is added to an emulsion of type II collagen (CII) and adjuvant. The IgG autoantibody activity to CII is increased, whereas no CII autoreactive T cells in vitro can be recorded. In this study, we have explored whether CD25+ cells inhibit T-cell autoreactivity to CII. We also followed the IgG anti-CII autoantibody activity and the IL-6 level in serum during the development of arthritis. BALB/c mice were coimmunized with bovine CII (BCII) and keyhole limpet haemocyanin (KLH) in complete Freund's adjuvant and boostered 3 weeks later. Control animals were immunized with either BCII or KLH. Sera were collected prior to and during the development of arthritis and examined for IgG anti-CII antibody activity and IL-6 content. When all BCII-KLH immunized mice had developed arthritis, splenocytes were prepared, with and without CD25+ cells, and tested for BCII reactivity in vitro. The serum IgG, IgG1 and IgG2a anti-CII antibody activities and the IL-6 level were significantly higher in BCII-KLH immunized mice than in BCII-immunized animals that failed to develop arthritis. The BCII-specific IL-2 secretion in vitro was significantly increased in CD25-depleted splenocyte cultures prepared from arthritic BCII-KLH-immunized mice. Development of arthritis in BALB/c mice induced by coimmunization with BCII/KLH results in increased levels of circulating IL-6 and IgG autoantibodies to CII. The arthritogenic BCII-KLH immunization potentiates BCII-specific IL-2 secretion by CD25-depleted splenocytes, but CD25+ cells hamper the outcome of their action, at least in vitro.
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