| 1. |
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| 2. |
- Lundstedt-Enkel, Katrin, et al.
(författare)
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A Statistical Resampling Method To Calculate Biomagnification Factors Exemplified with Organochlorine Data from Herring (Clupea harengus) Muscle and Guillemot (Uria aalge) Egg from the Baltic Sea
- 2005
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Ingår i: ENVIRONMENTAL SCIENCE & TECHNOLOGY. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 39:21, s. 8395-8402
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Tidskriftsartikel (refereegranskat)abstract
- A novel method for calculating biomagnification factors is presented and demonstrated using contaminant concentration data from the Swedish national monitoring program regarding organochlorine contaminants (OCs) in herring (Clupea harengus) muscle and guillemot (Uria aalge) egg, sampled from 1996 to 1999 from the Baltic Sea. With this randomly sampled ratios (RSR) method, biomagnification factors (BMFRSR) were generated and denoted with standard deviation (0) as a measure of the variation. The BMFRSR were calculated by randomly selecting one guillemot egg out of a total of 29 and one herring out of a total of 74, and the ratio was determined between the concentration of a given OC in that egg and the concentration of the same OC in that herring. With the resampling technique, this was performed 50 000 times for any given OC, and from this new distribution of ratios, BMFRSR for each OC were calculated and given as geometric mean (GM) with GM standard deviation (GMSD) range, arithmetic mean (AM) with AMSD range, and minimum (BMFMIN) as well as maximum (BMFMAX) biomagnification factors. The 14 analyzed OCs were p,p'DDT and its metabolites p,p'DDE and p,p'DDD, polychlorinated biphenyls (PCB congeners: CB28, CB52, CB101, CB118, CB138, CB153, and CB180), hexachlorocyclohexane isomers (alpha-, beta-, and gamma HCH), and hexachlorobenzene (HCB). Multivariate data analysis (MVDA) methods, including principal components analysis (PCA), partial least squares regression (PLS), and PLS discriminant analyses (PLS-DA), were first used to extract information from the complex biological and chemical data generated from each individual animal. MVDA were used to model similarities/dissimilarities regarding species (PCA, PLS-DA), sample years (PLS), and sample location (PLS-DA) to give a deeper understanding of the data that the BMF modeling was based upon. Contaminants that biomagnify, that had BMFRSR significantly higher than one, were p,p'DDE, CB118, HCB, CB138, CB180, CB153, beta HCH, and CB28. The contaminants that did not biomagnify were p,p'DDT, p,p'DDD, alpha HCH, CB101, and CB52. Eventual biomagnification for gamma HCH could not be determined. The BMFRSR for OCs present in herring muscle and guillemot egg showed a broad span with large variations for each contaminant. To be able to make reliable calculations of BMFs for different contaminants, we emphasize the importance of using data based upon large numbers of, as well as well-defined, individuals.
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| 3. |
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| 4. |
- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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| 5. |
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| 6. |
- Anastasopoulou, Stavroula, et al.
(författare)
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Acute central nervous system toxicity during treatment of pediatric acute lymphoblastic leukemia : phenotypes, risk factors and genotypes
- 2020
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Ingår i: Haematologica. - : Ferrata Storti Foundation. - 0390-6078 .- 1592-8721. ; 107:10, s. 2318-2328
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Tidskriftsartikel (refereegranskat)abstract
- Central nervous system (CNS) toxicity is common at diagnosis and during treatment of pediatric acute lymphoblastic leukemia (ALL). We studied CNS toxicity in 1,464 children aged 1.0-17.9 years, diagnosed with ALL and treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol. Genome-wide association studies, and a candidate single-nucleotide polymorphism (SNP; n=19) study were performed in 1,166 patients. Findings were validated in an independent Australian cohort of children with ALL (n=797) in whom two phenotypes were evaluated: diverse CNS toxicities (n=103) and methotrexate-related CNS toxicity (n=48). In total, 135/1,464 (9.2%) patients experienced CNS toxicity for a cumulative incidence of 8.7% (95% confidence interval: 7.31-10.20) at 12 months from diagnosis. Patients aged >= 10 years had a higher risk of CNS toxicity than had younger patients (16.3% vs. 7.4%; P < 0.001). The most common CNS toxicities were posterior reversible encephalopathy syndrome (n=52, 43 with seizures), sinus venous thrombosis (n=28, 9 with seizures), and isolated seizures (n=16). The most significant SNP identified by the genome-wide association studies did not reach genomic significance (lowest P-value: 1.11x10(-6)), but several were annotated in genes regulating neuronal functions. In candidate SNP analysis, ATXN1 rs68082256, related to epilepsy, was associated with seizures in patients < 10 years (P=0.01). ATXN1 rs68082256 was validated in the Australian cohort with diverse CNS toxicities (P=0.04). The role of ATXN1 as well as the novel SNP in neurotoxicity in pediatric ALL should be further explored.
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| 7. |
- Anastasopoulou, Stavroula, et al.
(författare)
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Does minimal central nervous system involvement in childhood acute lymphoblastic leukemia increase the risk for central nervous system toxicity?
- 2022
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Ingår i: Pediatric Blood & Cancer. - : John Wiley & Sons. - 1545-5009 .- 1545-5017. ; 69:7
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Tidskriftsartikel (refereegranskat)abstract
- Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) implicates enhanced intrathecal chemotherapy, which is related to CNS toxicity. Whether CNS involvement alone contributes to CNS toxicity remains unclear. We studied the occurrence of all CNS toxicities, seizures, and posterior reversible encephalopathy syndrome (PRES) in children with ALL without enhanced intrathecal chemotherapy with CNS involvement (n = 64) or without CNS involvement (n = 256) by flow cytometry. CNS involvement increased the risk for all CNS toxicities, seizures, and PRES in univariate analysis and, after adjusting for induction therapy, for seizures (hazard ratio [HR] = 3.33; 95% confidence interval [CI]: 1.26-8.82; p = 0.016) and PRES (HR = 4.85; 95% CI: 1.71-13.75; p = 0.003).
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| 8. |
- Anastasopoulou, Stavroula, et al.
(författare)
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Posterior reversible encephalopathy syndrome in children with acute lymphoblastic leukemia : Clinical characteristics, risk factors, course, and outcome of disease
- 2019
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Ingår i: Pediatric Blood & Cancer. - : WILEY. - 1545-5009 .- 1545-5017. ; 66:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Posterior reversible encephalopathy syndrome (PRES) is a distinct entity with incompletely known predisposing factors. The aim of this study is to describe the incidence, risk factors, clinical course, and outcome of PRES in childhood acute lymphoblastic leukemia (ALL).Procedure: Patients aged 1.0 to 17.9 years diagnosed with ALL from July 2008 to December 2015 and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol were included. Patients with PRES were identified in the prospective NOPHO leukemia toxicity registry, and clinical data were collected from the medical records.Results: The study group included 1378 patients, of whom 52 met the criteria for PRES. The cumulative incidence of PRES at one month was 1.7% (95% CI, 1.1-2.5) and at one year 3.7% (95% CI, 2.9-4.9). Older age (hazard ratios [HR] for each one-year increase in age 1.1; 95% CI, 1.0-1.2, P = 0.001) and T-cell immunophenotype (HR, 2.9; 95% CI, 1.6-5.3, P = 0.0005) were associated with PRES. Central nervous system (CNS) involvement (odds ratios [OR] = 2.8; 95% CI, 1.2-6.5, P = 0.015) was associated with early PRES and high-risk block treatment (HR = 2.63; 95% CI, 1.1-6.4, P = 0.033) with late PRES. At follow-up of the PRES patients, seven patients had epilepsy and seven had neurocognitive difficulties.Conclusion: PRES is a neurotoxicity in the treatment of childhood ALL with both acute and long-term morbidity. Older age, T-cell leukemia, CNS involvement and high-risk block treatment are risk factors for PRES.
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| 9. |
- Anastasopoulou, Stavroula, et al.
(författare)
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Seizures during treatment of childhood acute lymphoblastic leukemia : A population-based cohort study
- 2020
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Ingår i: European journal of paediatric neurology. - : ELSEVIER SCI LTD. - 1090-3798 .- 1532-2130. ; 27, s. 72-77
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Tidskriftsartikel (refereegranskat)abstract
- Background: Seizures are common in children with acute lymphoblastic leukemia (ALL). As ALL survival rates are improving, the challenge to minimize treatment related side effects and late sequelae rises. Here, we studied the frequency, timing, etiology and risk factors of seizures in ALL patients. Methods: The study included children aged 1-17.9 years at diagnosis of B-cell-precursor and T cell ALL who were treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol between 2008 and 2015. Detailed patient data were acquired from the NOPHO ALL2008 registry and by review of medical records. Results: Seizures occurred in 81/1464 (5.5%) patients. The cumulative incidence of seizures at one months was 1.7% (95% CI: 1.2-2.5) and at one year 5.3% (95% CI 4.2-6.5%). Patients aged 10-17.9 years, those with T cell immunophenotype, CNS involvement, or high-risk induction with dexamethasone had higher risk for seizures in univariable analyses. Only age remained a risk factor in multivariable analyses (the cumulative incidence of seizures for patients 10-17.9 years old at one year was 9.0% (95% CI: 6.2-12.9)). Of the 81 patients with seizures, 43 had posterior reversible encephalopathy syndrome (PRES), 15 had isolated seizures, nine had sinus venous thrombosis (SVT), three had stroke-like syndrome, and 11 had other neurotoxicities. Epilepsy diagnosis was reported in totally 11 ALL survivors at last follow up. Conclusion: Seizures are relatively common in ALL patients and occur most often in patients with PRES, SVT, or as an isolated symptom. Older children have higher risk of seizures. (C) 2020 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
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| 10. |
- Basu, Samar, et al.
(författare)
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Effects of melagatran, a novel direct thrombin inhibitor, during experimental septic shock
- 2000
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Ingår i: Expert Opinion on Investigational Drugs. - : Informa Healthcare. - 1354-3784 .- 1744-7658. ; 9:5, s. 1129-1137
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Tidskriftsartikel (refereegranskat)abstract
- Sepsis and endotoxaemia initiate the generation of thrombin, which is responsible for the conversion of fibrinogen to fibrin, platelet aggregation and acts as an inflammatory mediator affecting numerous types of cells, including myocardial, smooth muscle and endothelial cells. Human Gram-negative septic shock, frequently seen in intensive care units, is a condition with high mortality. This condition can be replicated in the endotoxaemic pig. As many of the toxic effects of sepsis are due to thrombin generation, it was of interest to study, using this porcine experimental septic shock model, whether inhibition of thrombin could alleviate the effects of endotoxaemia. For this purpose melagatran, a direct synthetic thrombin inhibitor with a molecular weight of 429 Da, was employed. Melagatran does not significantly interact with any other enzymes in the coagulation cascade or fibrinolytic enzymes aside from thrombin. Furthermore, melagatran does not require endogenous co-factors such as antithrombin or heparin co-Factor II for its antithrombin effect, which is important, as these inhibitors are often consumed in septic patients. We have shown that melagatran exerts a beneficial effect on renal function, as evaluated by plasma creatinine and urinary output, during experimental septic shock. These effects were most pronounced during the later phase of the experimental period, after the infusion of melagatran had been discontinued. Prevention of intrarenal coagulation may be attributable to this finding. In addition, melagatran had beneficial effects on systemic haemodynamics (left ventricular stroke work index, pulmonary capillary wedge pressure and systemic vascular resistance index) in endotoxaemic pigs. This result may be explained by the ability of melagatran to inhibit thrombin, thereby counteracting thrombin's cellular effects. Thus, it can be seen, using this experimental model of septic shock, that melagatran may help to alleviate some of the damaging effects of endotoxaemia, although more research is required to test this further.
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| 11. |
- Bejerot, Susanne, 1955-, et al.
(författare)
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The extreme male brain revisited: gender coherence in adults with autism spectrum disorder
- 2012
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Ingår i: British Journal of Psychiatry. - London, United Kingdom : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 201:2, s. 116-123
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Tidskriftsartikel (refereegranskat)abstract
- Background The 'extreme male brain' theory suggests that autism spectrum disorder (ASD) is an extreme variant of male intelligence. However, somewhat paradoxically, many individuals with ASD display androgynous physical features regardless of gender. Aims To assess physical measures, supposedly related to androgen influence, in adults with and without ASD. Method Serum hormone levels, anthropometry, the ratio of 2nd to 4th digit length (2D:4D) and psychiatric symptomatology were measured in 50 adults with high-functioning ASD and age- and gender-matched neurotypical controls. Photographs of face and body, as well as voice recordings, were obtained and assessed with respect to gender coherence, blindly and independently, by eight assessors. Results Women with ASD had higher total and bioactive testosterone levels, less feminine facial features and a larger head circumference than female controls. Men in the ASD group were assessed as having less masculine body characteristics and voice quality, and displayed higher (i.e. less masculine) 2D:4D ratios, but similar testosterone levels to controls. Androgynous facial features correlated strongly and positively with autistic traits measured with the Autism-Spectrum Quotient in the total sample. In males and females with ASD dehydroepiandrosterone sulfate did not decrease with age, in contrast to the control group. Conclusions Women with ASD had elevated testosterone levels and several masculinised characteristics compared with controls, whereas men with ASD displayed several feminised characteristics. Our findings suggest that ASD, rather than being characterised by masculinisation in both genders, may constitute a gender defiant disorder.
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| 12. |
- Bergström, Göran, 1964, et al.
(författare)
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Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
- 2021
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Ingår i: Circulation. - Philadelphia : American Heart Association. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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| 13. |
- Bergström, Göran, et al.
(författare)
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Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
- 2021
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Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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| 14. |
- Bladh, Mats, et al.
(författare)
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Staten, finansmarknaden och Stadshypotek
- 2002
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Ingår i: I takt och otakt med tiden. - : Ekerlids förlag, Stockholm. - 9189617193
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 15. |
- Cullberg, M., et al.
(författare)
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Pharmacokinetics of ximelagatran and relationship to clinical response in acute deep vein thrombosis
- 2005
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Ingår i: Clin Pharmacol Ther. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 77:4, s. 279-90
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Our objective was to characterize the pharmacokinetics of melagatran, the active form of the oral direct thrombin inhibitor ximelagatran, and the relationship between melagatran exposure and clinical outcome in patients with acute deep vein thrombosis. METHODS: A population pharmacokinetic analysis was performed on samples from patients with deep vein thrombosis participating in a randomized dose-finding study (THRombin Inhibitor in Venous thrombo-Embolism [THRIVE I]). Patients received fixed doses of oral ximelagatran (24, 36, 48, or 60 mg twice daily) for 12 to 16 days. Thrombus size was evaluated by venography before and after treatment. Exposure-response curves were characterized for the probability of regression, no change, and progression of the thrombus extension and of having a bleeding-related event, by use of logistic regression models. RESULTS: The pharmacokinetics of melagatran (1836 samples in 264 patients) was predictable, without significant time or dose dependencies. Clearance after oral administration (population mean, 27.3 L/h) was correlated with creatinine clearance (P < 10(-6)), and volume of distribution (population mean, 176 L) was correlated with body weight (P = 2 x 10(-5)). Gender, age, or smoking did not significantly influence melagatran pharmacokinetics after the influence of renal function and body weight was accounted for. Unexplained interpatient variability values in total plasma clearance and bioavailability were 19% and 21%, respectively. The median area under the plasma melagatran concentration versus time curve across all patients and dose levels was 3.22 h x micromol/L (5th-95th percentiles, 1.35-7.69). There was no significant relationship between area under the plasma concentration versus time curve and change in thrombus extension (P = .59) or bleeding-related events (P = .77), and the estimated exposure-response curves were relatively flat. CONCLUSIONS: The pharmacokinetics of melagatran in patients with acute deep vein thrombosis was predictable after oral ximelagatran administration. Shallow exposure-response curves for efficacy and bleeding indicate that there is no need for individualized dosing or therapeutic drug monitoring in the patient population studied.
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| 16. |
- Erikson, Martin G, et al.
(författare)
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Från Högskolan i Borås till Humboldt, volym 4
- 2018
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Denna rapport består av åtta kapitel baserade på en seminarieserie om akademiskt ansvar, som arrangerades av Högskolan i Borås under 2015 och 2016. Seminarierna utgjorde den fjärde omgången av de så kallade Humboldtseminarierna, som högskolan arrangerat i olika omgångar sedan 2010. Vid Humboldtseminarierna har aktuella frågor kring akademins möjligheter och utmaningar belysts utifrån olika teman, inte minst kopplat till samhällets förväntningar på forskning och högre utbildning. I det perspektivet blev akademiskt ansvar ett naturligt tema för den fjärde och avslutande omgången av Humboldtseminarierna. Just kopplingen till samhällsnytta är också en röd tråd igenom rapporten. Författarna skriver utifrån skilda erfarenheter som forskare, lärare och akademiska ledare – inte minst är rektorsperspektivet väl företrätt. Ett annat återkommande ämne är kopplingen mellan akademiskt ansvar och akademisk frihet, där ansvaret inte minst bidrar till att legitimera friheten. Kollegialitet är en viktig fråga för flera av författarna, både som princip för kvalitetsstyrning och som beslutsform. Sammantaget visar de olika bidragen att akademiskt ansvar berör många frågor av stor relevans för forskare, lärare, ledare och studenter, men också för intressenter utanför akademin. Där har författarnas bidrag goda möjligheter att ge nya insikter och inspirera till fortsatta diskussioner inom många olika områden.
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| 17. |
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| 18. |
- Eriksson, Göran, 1964-, et al.
(författare)
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Managing political crisis : an interactional approach to "image repair"
- 2012
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Ingår i: Journal of Communication Management. - : Emerald Group Publishing Limited. - 1363-254X .- 1478-0852. ; 16:3, s. 264-279
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Tidskriftsartikel (refereegranskat)abstract
- Purpose - The purpose of this paper is to extend the image repair theory by focusing on the largely ignored context of the face-to-face communication. The paper offers an exploratory study of how image repair work is carried out in interviews with politicians in the context of press conferences.Design/methodology/approach - The paper combines theoretical reflections with two qualitative case studies of press conferences of Swedish politicians. These press conferences were held to manage the challenge posed to the politicians’ public image by the media criticism. The analytical frame employed in this study is Conversation Analysis (CA).Findings - The way journalists act during interviews and how they pose questions have noticeable consequences for the accused actor´s image repair work. Image repair strategies like "apologizing" and "mortification" during the speech section of a press conference tend to be more effective as they give the accused greater opportunities to take control of the interaction.Research limitations/implications - Due to the exploratory nature of this interactional approach and the fact that the analysis involves only two cases, the findings must be seen as provisional.Practical implications - The knowledge of how journalists construct question is of high relevance for crisis communication and image repair work, and therefore of high value of public relations practitioners.Originality/value - The interactional approach to image repair offers a new theoretical frame for the understanding of crisis management in interview situations. The approach especially highlights the importance of journalists' questions in image repair work.
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| 19. |
- Eriksson, Jens, et al.
(författare)
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Characterization of motility and piliation in pathogenic Neisseria
- 2015
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Ingår i: BMC Microbiology. - : Springer Science and Business Media LLC. - 1471-2180. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: The type IV pili (Tfp) of pathogenic Neisseria (i. e., N. gonorrhoeae and N. meningitidis) are essential for twitching motility. Tfp retraction, which is dependent on the ATPase PilT, generates the forces that move bacteria over surfaces. Neisseria motility has mainly been studied in N. gonorrhoeae whereas the motility of N. meningitidis has not yet been characterized. Results: In this work, we analyzed bacterial motility and monitored Tfp retraction using live- cell imaging of freely moving bacteria. We observed that N. meningitidis moved over surfaces at an approximate speed of 1.6 mu m/s, whereas N. gonorrhoeae moved with a lower speed (1.0 mu/s). An alignment of the meningococcal and gonococcal pilT promoters revealed a conserved single base pair variation in the -10 promoter element that influence PilT expression. By tracking mutants with altered pilT expression or pilE sequence, we concluded that the difference in motility speed was independent of both. Live-cell imaging using total internal reflection fluorescence microscopy demonstrated that N. gonorrhoeae more often moved with fewer visible retracting filaments when compared to N. meningitidis. Correspondingly, meningococci also displayed a higher level of piliation in transmission electron microscopy. Nevertheless, motile gonococci that had the same number of filaments as N. meningitidis still moved with a lower speed. Conclusions: These data reveal differences in both speed and piliation between the pathogenic Neisseria species during twitching motility, suggesting a difference in Tfp-dynamics.
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| 20. |
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| 21. |
- Eriksson, Jens, 1980-, et al.
(författare)
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Difference in twitching motility between Neisseria meningitidis and Neisseria gonorrhoeae and its relation to pilus dynamics
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Type IV pili of pathogenic Neisseria, i. e. Neisseria gonorrhoeae and Neisseria meningitidis, are essential for initial attachment to host cells, induction of signal transduction cascades and disease development. A characteristic feature of type IV pili is their ability to retract, which generates forces that move bacteria over surfaces. However, the relation between bacterial motility and pilus dynamics remains poorly understood. In this work we analyzed bacterial motility and monitored movement of fluorescently labeled pili by live cell imaging. We found that movement of N. meningitidis occurred at higher speed and with a larger number of retracting pili than for N. gonorrhoeae. Analysis of time-lapse images suggested that N. gonorrhoeae most often moved using one retracting pilus, whereas N. meningitidis most often used four pili. There were no differences in the membrane distribution of PilT among strains. However, we found significantly higher levels of PilT in N. gonorrhoeae than in N. meningitidis. This produces a higher retraction probability, which could contribute to explaining the lower number of pili observed in N. gonorrhoeae. Finally, we propose a mechanism for how the speed of bacterial movement on a surface depends on the number of retracting pili.
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| 22. |
- Eriksson, Jesper, 1974, et al.
(författare)
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Early inequalities in excellent health and performance among young adult women and men in Sweden.
- 2007
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Ingår i: Gender medicine : official journal of the Partnership for Gender-Specific Medicine at Columbia University. - : Excerpta Medica, Inc.. - 1550-8579 .- 1878-7398. ; 4:2, s. 170-82
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although health inequality between young adult women and men has been strikingly evident in symptoms of ill health, we found no studies examining these inequalities with a focus on positive health and performance. OBJECTIVE: The aim of the present study was to examine possible inequalities between young adult women and men in a combined assessment of positive health and health-related performance. METHODS: Women and men aged 18 to 25 years studying medicine or computer science at 6 colleges/universities in 5 cities in Sweden were recruited for this study. All respondents answered a Web-based questionnaire regarding health, health-related performance, information and communication technology exposure, mood, and individual factors. A combined assessment of excellent health and health-related performance (EHHP) was defined and tested. Prevalence ratios (PRs) with 95% CIs of EHHP were calculated separately for female and male respondents. To assess potential determinants of EHHP, differences in the relationships between EHHP and the explanatory factors were compared for both sexes. Results: In a study group of young adult students consisting of 1046 women and 1312 men, women were less likely than men to have EHHP (PR 0.90 [95% CI, 0.83-0.98]). This inequality was even stronger within each course of study (medicine or computer science). Health-related factors showed similar patterns of relationship to EHHP for women and men; however, the strength of these relationships differed between the sexes. Logical relationships were observed between EHHP and almost all of the symptoms as well as between EHHP, the mood index, and health-related behavior. CONCLUSIONS: The well-known inequality in symptoms of ill health between young adult women and men was prevalent even in a combined assessment of positive health and health-related performance. That this inequality was prevalent in a relatively homogeneous sample of young adults indicates the importance of gender-based psychological and psychosocial factors beyond the more well-known structural gender-differentiating factors of vertical and horizontal segregation and disproportional responsibilities for domestic work. It may therefore be essential to emphasize these gender-based psychological and psychosocial factors when designing future studies and health promotion programs.
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| 23. |
- Eriksson, Johan, 1956-
(författare)
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Polybrominated diphenyl ethers and Tetrabromobisphenol A : Chemical synthesis, X-ray crystallography and Photochemical degradation
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the 1960s’ several manmade chemicals were detected in the environment, far from their sources. The most well known, and most likely those with the largest impact on the society, were DDT and its related compounds, and PCBs. These anthropogenic compounds were characterised as persistent organic pollutants (POPs). Following these POPs, several other chemicals have found their way to the environment. Over the last two decades, brominated flame retardants (BFRs) have become a matter of concern. Among all BFRs being commercially produced, tetrabromobisphenol A (TBBPA) and polybrominated diphenyl ethers (PBDEs) are the ones with the largest annual production. TBBPA is a very well defined compound while PBDEs consist of a large number of isomers and homologues (congeners). TBBPA does not seem to accumulate in biota as the PBDEs do, but is still of concern since it is found in e.g. sediments. The PBDEs can reach accumulation levels up in the ppm range. Still there is a lack of basic data for both TBBPA and PBDEs. Hence the present thesis is aimed to fill some of the data gaps by pursuing work on 1) photochemical degradation of TBBPA, some related compounds, and PBDEs; 2) synthesis of PBDE congeners and of TBBPA degradation products and 3) structural identifications of a selected set of BFRs by X-ray crystallography.An apparatus was designed for carrying out photochemical degradation test of chemicals in general but in particular for BFRs. Quantum yield, rate of degradation and to some extent, identification of degradation products were performed on TBBPA, the corresponding chlorinated compound and a number of TBBPA degradation products and on 15 single PBDE congeners. In order to make this work possible all three nonaBDE isomers were synthesised via a reductive pathway applying sodium borohydride as a reducing agent. The three nona-BDEs were all characterised by X-ray crystallography. The results of the photochemical degradation of TBBPA in water show a rapidly degradable compound also at pH’s that are environmentally relevant. Hence it is likely that TBBPA is not transported long distances, when exposed to sunlight, without undergoing photochemical degradation. It is notable that the TBBPA is degraded through cleavage between the two phenol rings. When the method was applied to study quantum yields and rate constants for the reaction of PBDE congeners it is evident that the decabromodiphenyl ether (BDE-209) is rapidly transformed. The reaction rate differ drastically from PBDEs with four or five bromine substituents that have very long half-lives when subjected to UV-light under the same conditions as for BDE-209. Lower brominated diphenyl ethers and polybrominated dibenzofurans were identified as PBDE degradation products. The synthesis of PBDEs and of TBBPA degradation products expanded the study as did the X-ray structure identifications.
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| 24. |
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| 25. |
- Eriksson, Jonas, et al.
(författare)
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Synthesis and preclinical evaluation of the CRTH2 antagonist [11C]MK-7246 as a novel PET tracer and potential surrogate marker for pancreatic beta-cell mass
- 2019
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Ingår i: Nuclear Medicine and Biology. - : Elsevier BV. - 0969-8051 .- 1872-9614. ; 71, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: MK-7246 is a potent and selective antagonist for chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). Within the pancreas CRTH2 is selectively expressed in pancreatic β-cells where it is believed to play a role in insulin release. Reduction in β-cell mass and insufficient insulin secretion in response to elevated blood glucose levels is a hallmark for type 1 and type 2 diabetes. Reported here is the synthesis of [11C]MK-7246 and initial preclinical evaluation towards CRTH2 imaging. The aim is to develop a method to quantify β-cell mass with PET and facilitate non-invasive studies of disease progression in individuals with type 2 diabetes.Methods: The precursor N-desmethyl-O-methyl MK-7246 was synthesized in seven steps and subjected to methylation with [11C]methyl iodide followed by hydrolysis to obtain [11C]MK-7246 labelled in the N-methyl position. Preclinical evaluation included in vitro radiography and immune-staining performed in human pancreatic biopsies. Biodistribution studies were performed in rat by PET-MRI and in pig by PET-CT imaging. The specific tracer uptake was examined in pig by scanning before and after administration of MK-7246 (1 mg/kg). Predicted dosimetry of [11C]MK-7246 in human males was estimated based on the biodistribution in rat.Results: [11C]MK-7246 was obtained with activities sufficient for the current investigations (270±120 MBq) and a radiochemical purity of 93±2%. The tracer displayed focal binding in areas with insulin positive islet of Langerhans in human pancreas sections. Baseline uptake in pig was significantly reduced in CRTH2-rich areas after administration of MK-7246; pancreas (66% reduction) and spleen (88% reduction). [11C]MK-7246 exhibited a safe human predicted dosimetry profile as extrapolated from the rat biodistribution data.Conclusions: Initial preclinical in vitro and in vivo evaluation of [11C]MK-7246 show binding and biodistribution properties suitable for PET imaging of CRTH2. Further studies are warranted to assess its potential in β-cell mass imaging and CRTH2 drug development.
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