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1.	Ladenvall, Per, 1972, et al. (författare) Genetic variation at the human connexin 43 locus but not at the connexin 40 locus is associated with left bundle branch block. 2015 Ingår i: Open heart. - : BMJ. - 2053-3624. ; 2:1 Tidskriftsartikel (refereegranskat)abstract Bundle branch block (BBB) has been regarded as a disease of the conduction system, but occurs in mice lacking connexin 40 (expressed in atria, proximal conduction system) or connexin 43 (expressed in Purkinje cells, cardiomyocytes).
2.	Sundström, Johan, Professor, 1971-, et al. (författare) Risk factors for subarachnoid haemorrhage : a nationwide cohort of 950 000 adults 2019 Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:6, s. 2018-2025 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium.METHODS: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries.RESULTS: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH.CONCLUSIONS: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.
3.	Eriksson, John, et al. (författare) Surgery and radiofrequency ablation for treatment of liver metastases from midgut and foregut carcinoids and endocrine pancreatic tumors 2008 Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 32:5, s. 930-938 Tidskriftsartikel (refereegranskat)abstract BACKGROUND:Many neuroendocrine tumors (NETs) have a tendency to metastasize to the liver. In case of limited number of metastases, liver surgery or radiofrequency ablation (RFA) may result in apparently total clearance of metastases. However, it is not clear whether such therapy will provide symptom reduction or increased survival.METHODS: Seventy-three patients with foregut (n=6) or midgut carcinoids (n=37) or endocrine pancreatic tumors (n=28), and two patients with NETs without discernable origin were studied. Symptoms were evaluated using a Symptom Severity Score. Liver surgery was performed in 42 operations and RFA on 205 lesions.RESULTS:Apparently total clearance of liver metastases was attained in 1 of 6 patients with foregut carcinoids, 15 of 37 with midgut carcinoids, and 13 of 28 with EPT. Symptom improvement was noted in 12 of 17 (70.6%) patients with carcinoid syndrome, and 75% also reduced their 5-HIAA and P-CgA by at least 50%. Patients with nonfunctioning EPT generally had no improvement of symptoms after surgical/RFA liver treatment, but eight patients had functioning EPT, and four of these reduced their biochemical markers by at least 50%. NETs with higher Ki67 index tended to recur more often. Complications occurred in 9 of 45 open surgery procedures, and in 8 of 203 RFA procedures.CONCLUSIONS:Treatment of liver metastases is successful in midgut carcinoid patients with limited liver metastases. Patients with foregut carcinoid and EPTs recur more often, possibly related to higher Ki67 index, and treatment of liver lesions less often reduces symptoms. Liver resections and RFA may be safely performed, and RFA is associated with few complications.
4.	Gustafsson, Jan-Eric, 1949, et al. (författare) School, Learning and Mental Health : A systematic review 2010 Rapport (övrigt vetenskapligt/konstnärligt)abstract Rapporten presenterar resultaten från en systematisk översikt av forskning om skola, lärande och barns psykiska hälsa. Kungliga Vetenskapsakademiens Hälsoutskottet har givit uppdraget att genomföra en sådan översikt till en arbetsgrupp som har arbetat med uppdraget från hösten 2008 till mars 2009. Det första syftet med översikten är att genomföra en kartläggning av forskning inom det breda fält som behandlar frågor om skola, lärande och barns och ungdomars psykiska hälsa. Det andra syftet är att genomföra en narrativ syntes av forskning som undersökt orsaksförhållanden mellan psykisk hälsa å ena sidan och skolresultat och lärande å den andra sidan. Det tredje syftet är att redovisa resultat från forskning som har studerat svenska barns och ungdomars erfarenheter och upplevelser av skola och undervisningssituationer. För att uppnå de första två syftena genomfördes systematiska litteratursökningar i bibliografiska databaser av artiklar publicerade i vetenskapliga internationella tidskrifter inom olika discipliner. Det tredje syftet undersöktes med litteratursökningar av kvalitativa svenska studier i bibliografiska databaser. Slutsatser På grundval dels av kartläggningen av forskning om skola, lärande och psykisk hälsa, dels av de två fördjupade översikterna kan följande slutsatser dras: • Omfattningen av forskning som undersöker relationerna mellan olika aspekter av skola och psykisk hälsa är begränsad och i synnerhet gäller detta forskning som undersöker organisationsfaktorer och undervisnings-faktorer, aktiviteter, läroplaners utformning, resurser, specialpedagogiskt stöd, och olika former av betyg och bedömning. • Tidiga svårigheter i skolan och i synnerhet läs- och skrivsvårigheter kan orsaka internaliserande och externaliserande psykiska problem. • Svårigheter i skola och psykiska problem tenderar att vara stabila över tid. • Skolrelaterade hälsoproblem tenderar att minska när eleverna börjar på gymnasiet och får tillgång till nya områden av aktiviteter, roller och valmöjligheter. • Att genomföra stora ansträngningar utan att detta leder till resultat är relaterat till utveckling av depression. Problem i skolan med skolresultat och prestationer orsakar inter-naliserande symptom för flickor under tonåren. • Det finns samband mellan olika typer av psykiska problem och de är också relaterade till ett brett spektrum av somatiska och psykosomatiska symptom. • Internaliserande och externaliserande psykiska problem har negativa effekter på skolprestationer genom mekanismer som är delvis ålders- och genusspecifika. • Kompetenser och prestationer i skolan är relaterade till psykisk hälsa. • Goda resultat i skolan har en positiv effekt på självuppfattning. • En god självuppfattning bidrar inte direkt till bättre resultat, men andra faktorer som är relaterade till självuppfattning (motivation och upplevd inre/yttre kontroll) påverkar lärande och resultat • Relationer med klasskamrater och lärare bidrar till processer som kopplar skolmisslyckande till psykisk ohälsa. Relationer med kamrater och lärare kan också skydda mot utvecklingen av psykiska problem. • Jämförelser med klasskamrater påverkar självuppfattningen, med effekter som varierar beroende på gruppsammansättning och typ av skola.
5.	Hägg, Daniel, 1974, et al. (författare) Expression profiling of macrophages from subjects with atherosclerosis to identify novel susceptibility genes. 2008 Ingår i: International journal of molecular medicine. - 1107-3756. ; 21:6, s. 697-704 Tidskriftsartikel (refereegranskat)abstract Although a number of environmental risk factors for atherosclerosis have been identified, heredity seems to be a significant independent risk factor. The aim of our study was to identify novel susceptibility genes for atherosclerosis. The screening process consisted of three steps. First, expression profiles of macrophages from subjects with atherosclerosis were compared to macrophages from control subjects. Secondly, the subjects were genotyped for promoter region polymorphisms in genes with altered gene expression. Thirdly, a population of subjects with coronary heart disease and control subjects were genotyped to test for an association with identified polymorphisms that affected gene expression. Twenty-seven genes were differentially expressed in both macrophages and foam cells from subjects with atherosclerosis. Three of these genes, IRS2, CD86 and SLC11A1 were selected for further analysis. Foam cells from subjects homozygous for the C allele at the -765C-->T SNP located in the promoter region of IRS2 had increased gene expression compared to foam cells from subjects with the nonCC genotype. Also, macrophages and foam cells from subjects homozygous for allele 2 at a repeat element in the promoter region of SLC11A1 had increased gene expression compared to macrophages and foam cells from subjects with the non22 genotype. Genotyping of 512 pairs of subjects with coronary heart disease (CHD) and matched controls revealed that subjects homozygous for C of the IRS2 SNP had an increased risk for CHD; odds ratio 1.43, p=0.010. Immunohistochemical staining of human carotid plaques showed that IRS2 expression was localised to macrophages and endothelial cells in vivo. Our method provides a reliable approach for identifying susceptibility genes for atherosclerosis, and we conclude that elevated IRS2 gene expression in macrophages may be associated with an increased risk of CHD.
6.	Mirzada, Naqibullah, 1977, et al. (författare) Multidisciplinary management of patent foramen ovale (PFO) and cryptogenic stroke/TIA 2013 Ingår i: Journal of Multidisciplinary Healthcare. - 1178-2390. ; 6, s. 357-363 Tidskriftsartikel (refereegranskat)abstract PURPOSE: Patent foramen ovale (PFO) has been implicated as a risk factor for cryptogenic ischemic stroke (CS). However, there is still a lack of widely accepted, undisputed indications for PFO closure. The present study describes the concept of the multidisciplinary PFO conference and a decision making process for closure versus no closure that was developed into a formalized clinical algorithm, and presents the results of implementing these, in terms of number and proportion of PFO closures as well as repeat referrals. DESIGN: Five specialists in neurology, cardiology, internal medicine, thromboembolism, and echocardiography evaluated the clinical data of 311 patients at PFO conferences during 2006 to 2009. The main criteria for closure were patients with first-ever CS with PFO and atrial septal aneurysm, or patients with recurrent CS and PFO without atrial septal aneurysm. RESULTS: A total of 143 patients (46%) were accepted for closure and 167 patients were rejected. Patients accepted for closure were younger (mean 50 years versus 58 years) (P < 0.001). The acceptance rate for PFO closure was similar throughout these years, with an average of 45%. Three of 167 patients (1.8%) initially rejected for PFO closure were re-referred due to recurrent stroke, and the PFO closure was subsequently performed. CONCLUSION: The acceptance rate of less than 50% in the present study underscores the complex relationship between CS and PFO. Whatever the criteria used for PFO closure, any unit caring for these patients needs to have a rigorous process to avoid overtreatment as well as undertreatment and to ensure that personal preferences and economic incentives do not steer the selection process. Our algorithm provides a stable acceptance rate and a low rate of repeat referrals.
7.	Mirzada, Naqibullah, 1977, et al. (författare) Quality of life after percutaneous closure of patent foramen ovale in patients after cryptogenic stroke compared to a normative sample 2018 Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 257, s. 46-49 Tidskriftsartikel (refereegranskat)abstract Aims: Despite the widespread use of percutaneous closure of patent foramen ovale (PFO) in patients after a cryptogenic stroke, little is known about its impact on health-related quality of life (HRQoL). The aim of this study was to assess HRQoL in these patients compared to PFO patients not considered candidates for percutaneous closure, and to a normal population. Methods and results: A total of 402 patients with cryptogenic stroke or transient ischaemic attack (TIA) who had been referred to our center for PFO closure were invited to a long-term clinical follow-up (mean follow-up 5.5 years; range 3-13 years). HRQoL was assessed using the SF-36 Health Survey and data were compared with an age-and gender-matched reference group from the Swedish SF-36 normative database. Fifteen patients had died and 43 did not answer the SF-36. Of the remaining 344 patients, 208 had undergone PFO closure, and 136 had not. The closure group and reference group reported similar HRQoL levels. However, the non-closure group showed significantly lower HRQoL in role limitation -physical, vitality, general health, mental health (p < 0.05) and social functioning (p = 0.05) than the reference group and also had significantly lower scores than the closure group, correcting for age differences, on physical functioning, role limitation - physical, vitality and general health (p < 0.05). Conclusions: Non-closure patients had lower HRQoL than their counterparts in the normal population and the closure group. Percutaneous PFO closure is associated with a favorable quality of life.
8.	Mirzada, Naqibullah, 1977, et al. (författare) Recurrent stroke in patients with patent foramen ovale: An observational prospective study of percutaneous closure of PFO versus non-closure 2015 Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 195, s. 293-299 Tidskriftsartikel (refereegranskat)abstract Aims: Observational studies favor percutaneous closure of patent foramen ovale (PFO) over medical therapy to reduce the risk of recurrent stroke, whereas randomized clinical trials have not shown significant differences. This study aims to compare long-term outcomes of PFO closure versus non-closure. Methods and results: Patients with PFO and stroke considered for PFO closure were invited to a long-term clinical follow-up. Of the 314 patients, 151 (48%) were accepted for closure and 163 (52%) were not accepted (mean age 50 vs. 58 years). The cumulative incidence of all-cause mortality, stroke or transient ischemic attacks (TIAs) for closure vs. non-closure under a mean follow-up time of five years was 10.6% (16 events) vs. 12.9% (21 events), p = 0.53. Six patients, 3.7% vs. 3.6%, died in each group, but no deaths were associated with PFO closure, recurrent stroke or TIA. The incidence of recurrent stroke or TIA for closure vs. non-closure was 6.6% (10 events) vs. 9.2% (15 events), p = 0.63. The respective event rates for stroke were 3.9% (6 events) vs. 5.5% (9 events), p = 0.50 and for TIA, 2.6% (4 events) vs. 3.7% (6 events), p = 0.59. Conclusion: PFO closure was associated with a low risk of recurrent events; however, compared to the non-closure group, no significant differences could be demonstrated. Careful patient selection can avoid under-as well as over-treatment of PFO patients. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
9.	Mirzada, Naqibullah, 1977, et al. (författare) Seven-year follow-up of percutaneous closure of patent foramen ovale 2013 Ingår i: IJC Heart and Vessels. - : Elsevier BV. - 2214-7632. ; 1, s. 32-36 Tidskriftsartikel (refereegranskat)abstract Background: Observational studies favor percutaneous closure of patent foramen ovale (PFO) over medical treatment to reduce recurrent stroke while randomized trials fail to demonstrate significant superiority of percutaneous PFO closure. Few long-term studies are available post PFO closure. This study reports long-term clinical outcomes after percutaneous PFO closure. Methods: Between 1997 and 2006, 86 consecutive eligible patients with cerebrovascular events, presumably related to PFO, underwent percutaneous PFO closure. All 86 patients were invited to a long-term follow-up, which was carried out during 2011 and 2012. Results: Percutaneous PFO closure was successfully performed in 85 of 86 patients. The follow-up rate was 100%. No cardiovascular or cerebrovascular deaths occurred. Two patients (both women) died from lung cancer during follow-up. Follow-up visits were conducted for 64 patients and the remaining 20 patients were followed up by phone. The mean follow-up time was 7.3. years (5 to 12.4. years). Mean age at PFO closure was 49. years. One patient had a minor stroke one month after PFO closure and a transient ischemic attack (TIA) two years afterwards. One other patient suffered from a TIA six years after closure. No long-term device-related complications were observed. Conclusions: Percutaneous PFO closure was associated with very low risk of recurrent stroke and is suitable in most patients. We observed no mortality and no long-term device-related complications related to PFO closure, indicating that percutaneous PFO closure is a safe and efficient treatment even in the long term. © 2013 Elsevier B.V.
10.	Almroth, Gabriel, 1953-, et al. (författare) Cyklophosphamide pulse treatment and infections in systemic vasculitis with renal involvement 2004 Ingår i: JASN 15 2004,2004. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
11.	Almroth, Gabriel, 1953-, et al. (författare) Långtidsresultat av cyklofosfamidbehandling vid ANCA-associerad systemisk vaskulit med njurengagemang 2004 Ingår i: Svenska Läkaresällskapets,2004. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
12.	Anfelter, P, et al. (författare) The effect of percutaneous dilatation of renal arterial stenosis on captopril renography in hypertension 2005 Ingår i: Blood Pressure. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 14:6, s. 359-365 Tidskriftsartikel (refereegranskat)abstract Background. The clinical effects of percutaneous transluminal renal artery angioplasty (PTRA) in patients with renal vascular stenosis and hypertension is controversial. Methods. We consecutively recruited all 23 patients referred for evaluation of renovascular hypertension that eventually underwent unilateral PTRA, to be investigated with captopril MAG3 renography (CR), both before and after the endovascular procedure. Data were evaluated on an intention-to-treat basis. Results. We found that the relative MAG3 clearance of the stenotic kidney increased (from 29.9 ± 14% to 35.1 ± 14%, p=0.01) and that the creatinine levels fell following the intervention (from 110 ± 19 to 99 ± 17 μmol/l, p=0.0003). Blood pressure levels were also lowered (from 173 ± 32/93 ± 17 to 158 ± 31/86 ± 15 mmHg, p<0.006) while the mean number of anti-hypertensive drugs was unchanged following PTRA (2.9 ± 1.4 before and 2.8 ± 1.3 drugs after the intervention, respectively, p-0.6). Conclusion. This prospective trial showed statistically significant improvements of individual kidney function as measured by CR and blood pressure in subjects with suspected renovascular hypertension treated with PTRA. Although the endovascular procedure was found to be safe, the magniture of the absolute improvements was rather modest. © 2005 Taylor & Francis.
13.	Appelgren, Daniel, 1985-, et al. (författare) Regulatory B cells are reduced in the blood in patients with granulomatosis with polyangiitis, and fail to regulate T-cell IFN-γproduction 2023 Ingår i: Clinical and Experimental Immunology. - : Oxford University Press. - 0009-9104 .- 1365-2249. ; 213:2, s. 190-201 Tidskriftsartikel (refereegranskat)abstract Regulatory B (Breg) cells can dampen inflammation, autoreactivity, and transplant rejection. We investigated the frequencies, phenotypes, and function of Breg cells in granulomatosis with polyangiitis (GPA) to gain further knowledge as to whether there are numerical alterations or limitations of their ability to regulate T-cell function. Frequencies and phenotypes of CD24hiCD27+ and CD24hiCD38hi B-cells in the blood were determined with flow cytometry in 37 GPA patients (22 in remission and 15 with active disease) and 31 healthy controls (HC). A co-culture model was used to study the capacity of Breg cells to regulate T-cell activation and proliferation in cells from 10 GPA patients in remission and 12 HC. T-cell cytokine production in vitro and levels in plasma were determined with enzyme-linked immunosorbent assay. Frequencies of CD24hiCD27+ B-cells were reduced both during active disease and remission compared with HC (P = 0.005 and P = 0.010, respectively), whereas CD24hiCD38hi B-cells did not differ. Patient CD24hiCD27+ B-cells exhibited decreased expression of CD25 but increased expression of PD-L1 and PD-L2 during remission. B-cells from GPA patients regulated T-cell proliferation but failed to regulate interferon (IFN)-γproduction (median T-cells alone 222 ng/ml vs. T-cells + B-cells 207 ng/ml, P = 0.426). IFN-γwas also elevated in patient plasma samples (P = 0.016). In conclusion, GPA patients exhibit altered numbers and phenotypes of CD24hiCD27+ B-cells. This is accompanied by a disability to control T-cell production of Th1-type cytokines during remission, which might be of fundamental importance for the granulomatous inflammation that characterizes the chronic phase of this disease. © 2023 The Author(s). Published by Oxford University Press on behalf of the British Society for Immunology.
14.	Berg, Johanna, et al. (författare) Making Archival Speech Recordings Accessible for Research : A Report from the Tilltal Project 2019 Ingår i: Svenska landsmål och svenskt folkliv. - : Kungl. Skogs- och Lantbruksakademien. - 0347-1837. ; 141, s. 171-178 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
15.	Dahlqvist, Johanna, 1979-, et al. (författare) Identification and functional characterization of a novel susceptibility locus for small vessel vasculitis with MPO-ANCA 2022 Ingår i: Rheumatology. - Oxford, United Kingdom : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:8, s. 3461-3470 Tidskriftsartikel (refereegranskat)abstract Objective To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV). Methods Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay. Results PR3-ANCA(+) AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P = 6.3 x 10(-61), odds ratio (OR) 0.10; rs9277341, P = 1.5 x 10(-44), OR 0.22] and with rs28929474 in the SERPINA1 gene (P = 2.7 x 10(-10), OR 2.9). MPO-ANCA(+) AAV was significantly associated with the HLA-DQB1/HLA-DQA2 locus (rs9274619, P = 5.4 x 10(-25), OR 3.7) and with a rare variant in the BACH2 gene (rs78275221, P = 7.9 x 10(-7), OR 3.0), the latter a novel susceptibility locus for MPO-ANCA(+) granulomatosis with polyangiitis/microscopic polyangiitis. The rs78275221-A risk allele reduced luciferase gene expression in endothelial cells, specifically, as compared with the non-risk allele. Conclusion We identified a novel susceptibility locus for MPO-ANCA(+) AAV and propose that the associated variant is of mechanistic importance, exerting a regulatory function on gene expression in specific cell types.
16.	Dalianis, Tina, et al. (författare) Management of BK-virus infection - Swedish recommendations 2019 Ingår i: Infectious Diseases. - : TAYLOR & FRANCIS LTD. - 2374-4235 .- 2374-4243. ; 51:7, s. 479-484 Forskningsöversikt (refereegranskat)abstract BK-virus (BKV) associated nephropathy (BKVAN) and BKV associated haemorrhagic cystitis (HC) are complications of BKV infection/reactivation in renal and allogeneic haematopoietic stem cell transplantation (HSCT) patients, respectively. The task of how to manage these diseases was given to the chair by the Swedish Reference Group for Antiviral Therapy (RAV). After individual contributions by members of the working group, consensus discussions were held in a meeting on 23 January 2018 arranged by RAV. Thereafter, the recommendations were published in Swedish on November 2018. The current translation to English has been approved by all co-authors. High BKV serum levels suggest an increased risk for BKVAN and potential graft failure. For detection of BKVAN, careful monitoring of BKV DNA levels in serum or plasma is recommended the first year after renal transplantation and when increased creatinine serum levels of unknown cause are observed. Notably, a renal biopsy is mandatory for diagnosis. To reduce the risk for progression of BKVAN, there is no specific treatment, and tailored individual decrease of immunosuppression is recommended. For BKV-HC, BKV monitoring is not recommended, since BK-viruria frequently occurs in HSCT patients and the predictive value of BKV in plasma/serum has not been determined. However, the risk for BKV-HC is higher for patients undergoing myeloablative conditioning, having an unrelated, HLA-mismatched, or a cord blood donor, and awareness of the increased risk and early intervention may benefit the patients. Also for BKV-HC, no specific therapy is available. Symptomatic treatment, e.g. forced diuresis and analgesics could be of use.
17.	Domeij, Rickard, 1958-, et al. (författare) Exploring the archives for textual entry points to speech - Experiences of interdisciplinary collaboration in making cultural heritage accessible for research 2020 Ingår i: CEUR Workshop Proceedings. - Riga : CEUR-WS. ; , s. 45-55, s. 45-55 Konferensbidrag (refereegranskat)abstract Tilltal (Tillgängligt kulturarv för forskning i tal, 'Accessible cultural heritage for speech research') is a multidisciplinary and methodological project undertaken by the Institute of Language and Folklore, KTH Royal Institute of Technology, and The Swedish National Archives in cooperation with the National Language Bank and SWE-CLARIN [1]. It aims to provide researchers better access to archival audio recordings using methods from language technology. The project comprises three case studies and one activity and usage study. In the case studies, actual research agendas from three different fields (ethnology, sociolinguistics and interaction analysis) serve as a basis for identifying procedures that may be simplified with the aid of digital tools. In the activity and usage study, we are applying an activity-theoretical approach with the aim of involving researchers and investigating how they use - and would like to be able to use - the archival resources at ISOF. Involving researchers in participatory design ensures that digital solutions are suggested and evaluated in relation to the requirements expressed by researchers engaged in specific research tasks [2]. In this paper we focus on one of the case studies, which investigates the process by which personal experience narratives are transformed into cultural heritage [3], and account for our results in exploring how different types of text material from the archives can be used to find relevant sections of the audio recordings. Finally, we discuss what lessons can be learned, and what conclusions can be drawn, from our experiences of interdisciplinary collaboration in the project.
18.	Eriksson, David, et al. (författare) Exploring opportunities for moral disengagement in codes of conduct from the textile industry 2018 Ingår i: World Review of Intermodal Transportation Research (WRITR). - 1749-4729 .- 1749-4737. ; 7:4, s. 371-389 Tidskriftsartikel (refereegranskat)abstract The purpose of this research is to assess how codes of conducts are outlined and formulated in relation to moral disengagement along the supply chain. The research is focused on the idea that supply chain structure may reduce the actors' sense of moral responsibility for the actions and impacts of the supply chain on workers and environment. The research has been conducted as a case study including Swedish firms in the textile industry. The research has used secondary data from codes of conducts. The findings show that codes of conduct do not cover all supply chain practices linked with moral disengagement. This does not cause immoral behaviour as such, but might cause moral disengagement. Supply chain research needs to focus on what should be included in codes of conduct and other ethical guidelines, so as to reduce the risk of immoral behaviour. In order to reduce the likelihood for moral disengagement, there are several supply chain practices that should be included in codes of conduct, such as power asymmetry, managerial support, and incentives.
19.	Eriksson, David, et al. (författare) Exploring opportunities for moral disengagement in codes of conduct from the textile industry 2018 Ingår i: World Review of Intermodal Transportation Research (WRITR). - : InderScience Publishers. - 1749-4729 .- 1749-4737. ; 7:4, s. 371-389 Tidskriftsartikel (refereegranskat)abstract The purpose of this research is to assess how codes of conducts are outlined and formulated in relation to moral disengagement along the supply chain. The research is focused on the idea that supply chain structure may reduce the actors' sense of moral responsibility for the actions and impacts of the supply chain on workers and environment. The research has been conducted as a case study including Swedish firms in the textile industry. The research has used secondary data from codes of conducts. The findings show that codes of conduct do not cover all supply chain practices linked with moral disengagement. This does not cause immoral behaviour as such, but might cause moral disengagement. Supply chain research needs to focus on what should be included in codes of conduct and other ethical guidelines, so as to reduce the risk of immoral behaviour. In order to reduce the likelihood for moral disengagement, there are several supply chain practices that should be included in codes of conduct, such as power asymmetry, managerial support, and incentives.
20.	Eriksson, Karin, 1976, et al. (författare) Pre-study on the establishment of a research collaboration between industrial energy systems and process control at Chalmers 2013 Rapport (övrigt vetenskapligt/konstnärligt)abstract The aim of the project described in this report has been to create a platform for collaboration between the research areas of industrial energy systems and process control at Chalmers. The authors of this report, belonging to the division of Heat and Power Technology, the Automatic control group and to CIT Industriell Energi, are convinced that a close collaboration between these areas could generate benefits for the process industry including •Improved efficiency with respect to energy•Improved opportunities to ensure satisfying operability•Improved process stability and product uniformity•Intensified utilization of available process equipment•Increased profitabilityIn accordance with the project scope, an inventory of relevant academic literature and of past and ongoing activities within the relevant research community has been conducted. Firstly, this inventory recognizes that researchers at Lehigh University (US), NTNU (Norway) and Carnegie Mellon University (US) have been strongly involved in the establishment of a research field commonly referred to as Integrated design and control. It is found that the research questions that are in the interest of the project partners largely can be attributed to this field. Other related labels used, and investigated as part of the project, are plant-wide control and heat exchanger network control. In a specific section of the report, definitions of important terms like operability, controllability and flexibility are given and commented on. Secondly, international research groups of special interest that has been identified are presented. In this category, I2C2 at University of Auckland and CAPEC at Technical University of Denmark can be mentioned. Relevant publications of the above mentioned research groups and their associates have been studied and are commented on in the report. Special emphasize has been put on review papers and on recent publications. Furthermore, the project has mapped the competences, experience and interest of the project partners. On this basis, the following keywords were identified:•Retrofit•Bio-based processes•Pulp and paper industry•Real life case studies•Industrial co-operation•Economic evaluation•Simulation•Scale up challengesThis list was used during discussions on research questions and project ideas for future collaboration. This project has provided the partners an opportunity to obtain deeper insight into each other’s knowledge and experiences, and, moreover, research areas of common interest have been recognized. To further develop the collaboration, the next step seems to imply joint participation in specific research projects. Research questions of interest and ideas for future projects are presented in the full report. This relates to the prevailing possibilities to apply for research grant - an issue that is addressed lastly in this report. In relation to this it should be noted that there is a program on Industrial Process Automation, supported by Vinnova, the Swedish Energy Agency and Formas, that is soon to be launched. A strategy for monitoring calls from this program as well as other relevant programs was formulated. As a result of the work in this project, it has also been possible to formulate proposals for two specific PhD-student projects within the Preem-Chalmers cooperation. These proposals take the outcome of this project into account and include opportunities to further develop the collaboration between industrial energy systems and process control at Chalmers.
21.	Eriksson, Maja, 1975, et al. (författare) Comparing mono- and divalent DNA groove binding cyanine dyes--Binding geometries, dissociation rates, and fluorescence properties 2006 Ingår i: Biophysical Chemistry. - : Elsevier BV. - 1873-4200 .- 0301-4622. ; 122:3, s. 195-205 Tidskriftsartikel (refereegranskat)abstract The unsymmetrical cyanine dyes BOXTO-PRO and BOXTO-MEE were derived from the DNA groove binder BOXTO, by adding a positively charged or a non-ionic hydrophilic tail to BOXTO, respectively. The main objective was to obtain more efficient DNA probes, for instance in electrophoresis and microscopy, by slowing down the dissociation of BOXTO from DNA. The interactions with mixed sequence DNA was studied with fluorescence and absorbance spectroscopy, stopped-flow dissociation and gel electrophoresis. Both the derivatives are groove bound as BOXTO, and have similar fluorescence properties when bound to mixed sequence DNA in free solution. BOXTO-PRO exhibits a slower dissociation than BOXTO from DNA, whereas the dissociation rate for BOXTO-MEE is faster and, unexpectedly independent of the ionic strength. During gel electrophoresis both BOXTO-PRO and BOXTO-MEE exhibit a faster dissociation rate than BOXTO. Still, BOXTO-PRO seems to be a good alternative as DNA probe, especially for applications in free solution where the dissociation is slower than for the corresponding intercalator TOPRO-1.
22.	Eriksson, Per, 1958- (författare) Nine patients with anti-neutrophil cytoplasmic antibody-positive vasculitis successfully treated with rituximab 2005 Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 257:6, s. 540-548 Tidskriftsartikel (refereegranskat)abstract Objectives. Rituximab (RIT) is a monoclonal anti-CD20 antibody, which depletes B-lymphocytes but not plasma cells. RIT is used for treatment of B-cell lymphomas, but has also shown beneficial effects in autoimmune diseases. In this case series RIT was used in anti-neutrophil cytoplasmic antibody (ANCA)-positive vasculitis. Design. Case series with a structured follow-up of treated patients. Setting. Departments of Nephrology and Rheumatology of a university hospital. Subjects. Two women with myeloperoxidase-ANCA-positive microscopic polyangiitis and seven patients (five men and two women) with proteinase 3-ANCA-positive Wegener's granulomatosis. All patients were resistant to conventional therapy or had relapsed repeatedly after cessation of cyclophosphamide (Cyc). Interventions. The cases were treated with intravenous infusions of RIT once a week two times (three cases) or four times (six cases). To prevent formation of antibodies to RIT, mycophenolate mofetil (five patients), azathioprine (one patient), or a short course of Cyc (two patients) were added or allowed to continue. Mainoutcome measures. Remission at 6 months assessed with Birmingham vasculitis activity score. The cases were followed 6-24 months and relapse rate was also noted. Results. Eight of nine patients responded completely and one case responded partially. Pulmonary X-ray improved (four cases), progress of lower extremity gangrene stopped (one case), remission of neuropathy was stable (one patient), renal vasculitis went into remission (two cases), and severe musculoskeletal pain improved (one case). Minor relapse in the nose occurred in two cases. No adverse events or major infections were noted. Conclusion. RIT seems promising and safe in ANCA-positive vasculitis, and controlled studies should be conducted. © 2005 Blackwell Publishing Ltd.
23.	Eriksson, Per, 1958-, et al. (författare) Relationship between serum levels of IL-18 and IgG1 in patients with primary Sjögren's syndrome, rheumatoid arthritis and healthy controls 2004 Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 137:3, s. 617-620 Tidskriftsartikel (refereegranskat)abstract Primary Sjögren's syndrome (SS) is characterized by inflammation in salivary and lachrymal glands, with a local predominance of Th1-like cytokines, as well as the pleiotropic cytokine interleukin (IL) 18. High serum levels of polyclonal IgG are common, with a subclass imbalance in which IgG1 is increased and IgG2 is normal or low. IL-18 is also of pathogenetic importance in rheumatoid arthritis. In the present study we looked for any relationship between serum IL-18 as well as transforming growth factor (TGF) β1 versus IgA, IgM, and IgG subclass levels in SS (n = 16), rheumatoid arthritis (RA) (n = 15), and healthy controls (n = 15). SS was defined by the revised American-European classification criteria. IL-18 and TGF-β1 were analyzed with enzyme immunoassays (EIA), and IgG1, IgG2 and IgG3 by single radial immunodiffusion. In the composite group of RA, SS and normal controls, IgG1 and IL-18 were related (R = 0.52, P = 0.0005). No relation was found neither between IL-18 versus IgG2, IgG3 or IgA, nor between serum TGF-β1 versus any of the immunoglobulins. Since serum levels of IL-18 are related to serum IgG1, IL-18 may be of importance for IgG1 switch and/or release.
24.	Eriksson, Per, 1958- (författare) Renal disease in primary Sjögren's syndrome 1996 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Primary Sjögren's syndrome (SS) is characterised by inflammation in the lacrimal and salivary glands. The kidneys may be involved, e.g. tubulointerstitial nephritis (TIN) and distal renal tubular acidosis (dRTA). dRTA is often associated with hypocitraturia, and both represent risk factors for the development of urolithiasis. The present investigations were undertaken to evaluate renal tubular function (including -dRTA), glomerular filtration rate (GFR), renal histopathology and mechanisms of stone formation, as well as the serum IgG subclass pattern in patients with SS. Furthermore, patients presenting with urolithiasis and dRTA in absence of sicca symptoms, as well as patients with urolithiasis andhypocitraturia, were studied with respect to autoantibodies and clinical features of SS. Renal tubular dysfunction, such as dRTA; impaired urine concentrating ability; hypocitraturia; and decreased tubular reabsorption of phosphate (1RP%), was conunonly detected in the SS-patients. Tubular proteinuria (al-microglobulin) and tubular enzymuria (NAG) were primarily associated with decreased GFR. GFR, investigated with 5Icr-EDTA plasma clearance, was below the reference limit in 33% of SS-patients. An inverse correlation was found between GFR and the extent of tubulointerstitial nephritis (adjusted CTIN score). Decreased GFR was mostly due to TIN, although urolithiasis and upper urinary tract infections may have contributed in some patients. TIN was demonstrated in most biopsied patients with SS, and the histopathological picture was characterised by mainly focal interstitial inflanunation, tubular atrophy, interstitial fibrosis and a varying extent of glomerular sclerosis. Fourty-one percent of the SS-patients had formed at least one stone, and calcium phosphate was the main constituent in most stones. All stone formers had dRTA, and most of them had hypocitraturia. Urinary calcium and urate excretion was also significantly higher than in non-stone formers. The SS-patients often had low serum levels of IgG2, despite high levels of total IgG. Low levels of IgG2 were sometimes associated with infections. A high IgG lngG2 ratio indicated autoimmune disease. Of 10 patients presenting with urolithiasis and dRTA, anti-SS-A antibodies were detected in eight. Subjective sicca symptoms subsequently developed l-48 years after the presentation of urolithiasis, and objective signs of SS were found in 7 patients. In a large population of hypocitraturic stone formers, ANA and anti-SS-A antibodies were commonly detected in the women but not in the men. Four of 14 evaluated hypocitraturic women with anti-SS-A antibodies or ANA, fulfilled the criteria for SS. In conclusion, the present investigations show that 24-hour urinary excretion of citrate is a valuable tool for detection of renal disease in SS, slightly-moderately decreased GFR is not unusual in SS-patients with. renal disease, the "adjusted CTIN score" can be a useful tool for quantifying the extent of tu'bulointerstitial nephritis, and the urine composition in stone formers with SS is similar to that of other dRT A-patients. The possibility of a Sjögren-related renal disease charcterised by urolithiasis and/or dRTA and antibodies to SS-A, regardless of whether subjective sicca symptoms are present or not, is hypothesised.
25.	Eriksson, Per, 1958-, et al. (författare) Sjögren´s syndrome with myalgia is associated with subnormal secretion of cytokines by peripheral blood mononuclear cells. 2004 Ingår i: Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 31, s. 729-735 Tidskriftsartikel (refereegranskat)
26.	Eriksson, Per, et al. (författare) Successful Treatment of AA Amyloidosis in Ankylosing Spondylitis Using Tocilizumab: Report of Two Cases and Review of the Literature 2021 Ingår i: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 8 Forskningsöversikt (refereegranskat)abstract Historically, secondary amyloidosis has been a feared complication of chronic inflammatory conditions. The fibril protein AA derives from the acute phase reactant serum amyloid A (SAA). Long-term elevation of SAA levels remains a major risk factor for the development of AA amyloidosis in rheumatic diseases, and the prognosis may be unpredictable. Nowadays, with increased availability of effective biological agents, the incidence of AA amyloidosis seems to be declining. Still, genetically predisposed subjects with slowly progressive disease and mild symptoms combined with ongoing systemic inflammation may be at risk. Interleukin-6 (IL-6) is one of the drivers of SAA release and effectiveness of the humanized anti-IL-6 receptor antibody tocilizumab (TCZ) for the treatment of AA amyloidosis has been observed in some rheumatic conditions. Herein, we report two male subjects with longstanding ankylosing spondylitis (AS) complicated by renal amyloidosis who received TCZ with rapid and beneficial effects regarding inflammation and proteinuria. To the best of our knowledge, the use of TCZ in AS patients with this extra-articular manifestation has not previously been described. The paper includes histopathology, clinical follow-up, and longitudinal data of the two cases along with a comprehensive review of relevant literature. Mechanisms behind amyloid-mediated tissue damage and organ dysfunction are discussed. Altogether, our data highlight that blocking IL-6 signaling may represent a promising therapeutic option in patients with renal AA amyloidosis.
27.	Eriksson, Per, 1958-, et al. (författare) Systemisk vaskulit 2018. - 6 Ingår i: Internmedicin. - Stockholm : Liber. - 9789147113262 ; , s. 939-949 Bokkapitel (övrigt vetenskapligt/konstnärligt)
28.	Farjana, Sadia, 1983, et al. (författare) Realizing a 140 GHz Gap Waveguide–Based Array Antenna by Low-Cost Injection Molding and Micromachining 2021 Ingår i: Journal of Infrared, Millimeter and Terahertz Waves. - : Springer. - 1866-6892 .- 1866-6906. ; 42:8, s. 893-914 Tidskriftsartikel (refereegranskat)abstract This paper presents a novel micromachining process to fabricate a 140 GHz planar antenna based on gap waveguide technology to be used in the next-generation backhauling links. The 140 GHz planar array antenna consists of three layers, all of which have been fabricated using polymer-based microfabrication and injection molding. The 140 GHz antenna has the potential to be used as an element in a bigger 3D array in a line-of-sight (LOS) multiple input multiple output (MIMO) configuration to boost the network capacity. In this work, we focus on the fabrication of a single antenna array element based on gap waveguide technology. Depending on the complexity of each antenna layer’s design, three different micromachining techniques, SU8 fabrication, polydimethylsiloxane (PDMS) molding, and injection molding of the polymer (OSTEMER), together with gold (Au) coating, have been utilized to fabricate a single 140 GHz planar array antenna. The input reflection coefficient was measured to be below − 11 dB over a 14% bandwidth from 132 to 152 GHz, and the antenna gain was measured to be 31 dBi at 140 GHz, both of which are in good agreement with the simulations. © 2021, The Author(s).
29.	Fjellström, Mona, 1958-, et al. (författare) Fakultetsaudit : Intern bedömning av kvalitetsarbete för utbildning på grund- och avancerad nivå vid Teknisk-naturvetenskaplig fakultet hösten 2016 2017 Rapport (populärvet., debatt m.m.)
30.	Geetha, Duvuru, et al. (författare) Rituximab for treatment of severe renal disease in ANCA associated vasculitis 2016 Ingår i: JN. Journal of Nephrology. - : Springer. - 1121-8428 .- 1724-6059. ; 29:2, s. 195-201 Tidskriftsartikel (refereegranskat)abstract BackgroundRituximab (RTX) is approved for remission induction in ANCA associated vasculitis (AAV). However, data on use of RTX in patients with severe renal disease is lacking.MethodsWe conducted a retrospective multi-center study to evaluate the efficacy and safety of RTX with glucocorticoids (GC) with and without use of concomitant cyclophosphamide (CYC) for remission induction in patients presenting with e GFR less than 20 ml/min/1.73 m2. We evaluated outcomes of remission at 6 months (6 M), renal recovery after acute dialysis at diagnosis, e-GFR rise at 6 M, patient and renal survival and adverse events.ResultsA total 37 patients met the inclusion criteria. The median age was 61 years. (55–73), 62 % were males, 78 % had new diagnosis and 59 % were MPO ANCA positive. The median (IQR) e-GFR at diagnosis was 13 ml/min/1.73 m2 (7–16) and 15 required acute dialysis. Eleven (30 %) had alveolar hemorrhage. Twelve (32 %) received RTX with GC, 25 (68 %) received RTX with GC and CYC and seventeen (46 %) received plasma exchange. The median (IQR) follow up was 973 (200–1656) days. Thirty two of 33 patients (97 %) achieved remission at 6 M and 10 of 15 patients (67 %) requiring dialysis recovered renal function. The median prednisone dose at 6 M was 6 mg/day. The mean (SD) increase in e-GFR at 6 months was 14.5 (22) ml/min/m2. Twelve patients developed ESRD during follow up. There were 3 deaths in the first 6 months. When stratified by use of concomitant CYC, there were no differences in baseline e GFR, use of plasmapheresis, RTX dosing regimen or median follow up days between the groups. No differences in remission, renal recovery ESRD or death were observed.ConclusionsThis study of AAV patients with severe renal disease demonstrates that the outcomes appear equivalent when treated with RTX and GC with or without concomitant CYC.
31.	Giang, Kok Wai, 1984, et al. (författare) Long-Term Risk of Hemorrhagic Stroke in Young Patients With Congenital Heart Disease 2018 Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 49:5, s. 1155-1162 Tidskriftsartikel (refereegranskat)abstract Background and Purpose-The risk of ischemic stroke is increased in patients with congenital heart disease (CHD); however, data on the risk of hemorrhagic stroke, including intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH), are lacking. Methods-The Swedish Patient Register was used to identify all patients who were born with a diagnosis of CHD between 1970 and 1993. Each patient was compared with 10 randomly selected controls from the general population, matched for age, sex, and county. Follow-up data were collected until December 2011 for both cases and controls. Results-Of 21 982 patients with CHD, 70 developed ICH and 57 developed SAH up to the age of 42 years. CHD patients had more than an 8x higher risk (incidence rate ratio, 8.23; 95% confidence interval, 6-11.2) of developing ICH and almost an 8x higher risk of developing SAH (incidence rate ratio, 7.64; 95% confidence interval, 5.41-10.7) compared with controls. The absolute risk of ICH and SAH was low, with incidence rates of 1.18 and 0.96 cases per 10 000 person-years, respectively. Patients with severe nonconotruncal defects (incidence rate ratio, 16.5; 95% confidence interval, 5.63-51.2) or coarctation of the aorta (incidence rate ratio, 17.3; 95% confidence interval, 6.63-51.8) had the highest relative risk of developing hemorrhagic stroke, with incidence rates of 3.22 and 2.79 cases per 10 000 person-years, respectively. Conclusions-The relative risk of hemorrhagic stroke among children and young adults with CHD was almost 8x higher than that of matched controls from the general population, although the absolute risk was low. The highest risk of ICH and SAH occurred in patients with severe nonconotruncal defects and coarctation of the aorta.
32.	Ivanov, S.A., et al. (författare) Ba3Fe2WO9-delta : Effect of oxygen non-stoichiometry on structural and magnetic properties 2006 Ingår i: Journal of Solid State Chemistry. - : Elsevier BV. - 0022-4596 .- 1095-726X. ; 179:8, s. 2645-2655:8, s. 2645-2655 Tidskriftsartikel (refereegranskat)abstract The magnetic and structural properties of oxygen-deficient perovskites with composition Ba3Fe2WO9-6 (BFWO) have been systematically studied for two different oxygen contents corresponding to delta = 0.00 and 0.55 in the chemical formula in order, to determine and correlate their chemical composition, structural and magnetic properties. The evolution of nuclear and magnetic structures with temperature has been investigated by neutron powder diffraction. It was shown that at room temperature the stoichiometric compound (delta = 0.00) adopts a hexagonal 6H-perovskite structure (space group P6(3)/mmc). This phase, when heated at high temperature under a stream of Ar gas, transforms to an oxygen-deficient phase delta = 0.55), which is an ordered cubic perovskite structure (space group Fm-3m). The crystallographic and magnetic properties of the obtained phases are compared, and it is clear that the magnetic properties are significantly affected by oxygen non-stoichiometry. These changes of magnetic properties for such a slight decrease in oxygen content are interpreted as a result of structural transformations. Together with the experimental results based on neutron powder diffraction data a discussion of some aspects of the structural transformation (P6(3)/mmc -> Fm-3m) is presented.
33.	Johannesson, Kerstin, 1955, et al. (författare) Ten years of marine evolutionary biology - challenges and achievements of a multidisciplinary research initiative 2023 Ingår i: Evolutionary Applications. - : Wiley. - 1752-4571. ; 16:2, s. 530-41 Tidskriftsartikel (refereegranskat)abstract The Centre for Marine Evolutionary Biology (CeMEB) at the University of Gothenburg, Sweden, was established in 2008 through a 10-year research grant of 8.7 m€ to a team of senior researchers. Today, CeMEB members have contributed >500 scientific publications, 30 PhD theses and have organised 75 meetings and courses, including 18 three-day meetings and four conferences. What are the footprints of CeMEB, and how will the centre continue to play a national and international role as an important node of marine evolutionary research? In this perspective arcticle we first look back over the 10 years of CeMEB activities and briefly survey some of the many achievements of CeMEB. We furthermore compare the initial goals, as formulated in the grant application, with what has been achieved, and discuss challenges and milestones along the way. Finally, we bring forward some general lessons that can be learnt from a research funding of this type, and we take also look ahead, discussing how CeMEB’s achievements and lessons can be used as a springboard to the future of marine evolutionary biology.
34.	Johnson, Magnus S.C. 1969, et al. (författare) Interaction of scavenger receptor class B type I with peroxisomal targeting receptor Pex5p. 2003 Ingår i: Biochemical and biophysical research communications. - 0006-291X. ; 312:4, s. 1325-34 Tidskriftsartikel (refereegranskat)abstract Scavenger receptor class B type I (SR-BI) is an HDL receptor that mediates selective HDL lipid uptake. Peroxisomes play an important role in lipid metabolism and peroxisomal targeting signal type 1 (PTS1)-containing proteins are translocated to peroxisomes by the peroxisomal targeting import receptor, Pex5p. We have previously identified a PTS1 motif in the intracellular domain of rat SR-BI. Here, we examine the possible interaction between Pex5p and SR-BI. Expression of a Flag-tagged intracellular domain of SR-BI resulted in translocation to the peroxisome as demonstrated by double labeling with anti-Flag IgG and anti-catalase IgG analyzed by confocal microscopy. Immunoprecipitation experiments with anti-SR-BI antibody showed that Pex5p co-precipitated with SR-BI. However, when an antibody against Pex5p was used for immunoprecipitation, only the 57kDa, non-glycosylated form, of SR-BI co-precipitated. We conclude that the PTS1 domain of SR-BI is functional and can mediate peroxisomal interaction via Pex5p, in vitro.
35.	Karlsson, Maths, 1978, et al. (författare) Using Neutron Spin-Echo To Investigate Proton Dynamics in Proton-Conducting Perovskites 2010 Ingår i: Chemistry of Materials. - : American Chemical Society (ACS). - 1520-5002 .- 0897-4756. ; 22:3, s. 740-742 Tidskriftsartikel (refereegranskat)abstract The applicability and potential of neutron spin-echo (NSE) to study proton dynamics in proton-conducting ceramics was studied. The experiment was performed on hydrated BaZr 0,90 Y 0.10 O 2.95 (10Y:BZO), a cubic perovskite with a relatively high proton conductivity. The NSE experiment was performed at the IN15 spectrometer at Institut Laue-Langevin (ILL) in Grenoble, France. The relaxation rate for two Q-values for the temperature 563 K was determined. The first-principles calculations were carried out within the framework of density functional theory (DFT). The calculated diffusion harriers far from Y-dopants are found to he 0.20 and 0.18 eV for the proton transfer and hydroxyl rotation motion, respectively. The binding energy to a Y-dopant is 0.16 eV, and the influence of the Y-dopant on the energetics for the proton is quite extended in space, including both the first and the second coordination shells.
36.	Karlsson, Maths, 1978, et al. (författare) Vibrational Properties of Protons in Hydrated BaInxZr1-xO3-x/2 2005 Ingår i: Physical Review B - Condensed Matter and Materials Physics. - 2469-9950 .- 2469-9969. ; 72, s. 1-7 Tidskriftsartikel (refereegranskat)abstract We investigate the local proton dynamics in the proton conducting hydrated perovskite system BaInxZr1-xO3-x/2 (x=0.25-0.75) using infrared spectroscopy and first-principles calculations. We show that oxygen vacancies and dopant atoms in the vicinity of the proton tilt the proton toward a neighboring oxygen creating strongly hydrogen-bonded configurations. This is manifested as a strong redshift of the O-H stretch band in the infrared absorption spectrum. We also find considerable fluctuations of the nearest and next-nearest oxygen-proton distances with time, resulting in additional spectral broadening. By comparing the frequencies of computed O-H stretch modes we can relate specific local configurations to different parts of the broad O-H stretch band. Even though hydrogen-bonded configurations favor proton transfer they hinder the long-range migration by decreasing the reorientational rate. Thus, in order to optimize the proton mobility it is important to avoid extreme configurations caused by either oxygen vacancies or dopant atoms in the perovskite structure.
37.	Kottyan, Leah C., et al. (författare) The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share. 2015 Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:2, s. 582-596 Tidskriftsartikel (refereegranskat)abstract Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5-TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5-TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls. The genetic effect from the IRF5 promoter can be explained by any one of four variants in 5.7 kb (P-valuemeta = 6 × 10(-49); OR = 1.38-1.97). The second genetic effect spanned an 85.5-kb, 24-variant haplotype that included the genes IRF5 and TNPO3 (P-valuesEU = 10(-27)-10(-32), OR = 1.7-1.81). Many variants at the IRF5 locus with previously assigned biological function are not members of either final credible set of potential causal variants identified herein. In addition to the known biologically functional variants, we demonstrated that the risk allele of rs4728142, a variant in the promoter among the lowest frequentist probability and highest Bayesian posterior probability, was correlated with IRF5 expression and differentially binds the transcription factor ZBTB3. Our analytical strategy provides a novel framework for future studies aimed at dissecting etiological genetic effects. Finally, both SLE elements of the statistical model appear to operate in Sjögrens syndrome and systemic sclerosis whereas only the IRF5-TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF5-TNPO3.
38.	Kurtovic, Sanela, et al. (författare) Diverging alternative splicing fingerprints in the transforming growth factor-β signaling pathway identified in thoracic aortic aneurysms. 2011 Ingår i: Molecular medicine (Cambridge, Mass.). - : Springer Science and Business Media LLC. - 1528-3658 .- 1076-1551. ; 17:7-8, s. 665-75 Tidskriftsartikel (refereegranskat)abstract Impaired regulation of the transforming growth factor-β (TGFβ) signaling pathway has been linked to thoracic aortic aneurysm (TAA). Previous work has indicated that differential splicing is a common phenomenon, potentially influencing the function of proteins. In the present study we investigated the occurrence of differential splicing in the TGFβ pathway associated with TAA in patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV). Affymetrix human exon arrays were applied to 81 intima/media tissue samples from dilated (n = 51) and nondilated (n = 30) aortas of TAV and BAV patients. To analyze the occurrence of alternative splicing in the TGFβ pathway, multivariate techniques, including principal component analysis and OPLS-DA (orthogonal partial least squares to latent structures discriminant analysis), were applied on all exons (n = 614) of the TGFβ pathway. The scores plot, based on the splice index of individual exons, showed separate clusters of patients with both dilated and nondilated aorta, thereby illustrating the potential importance of alternative splicing in TAA. In total, differential splicing was detected in 187 exons. Furthermore, the pattern of alternative splicing is clearly differs between TAV and BAV patients. Differential splicing was specific for BAV and TAV patients in 40 and 86 exons, respectively, and splicings of 61 exons were shared between the two phenotypes. The occurrence of differential splicing was demonstrated in selected genes by reverse transcription-polymerase chain reaction. In summary, alternative splicing is a common feature of TAA formation. Our results suggest that dilatation in TAV and BAV patients has different alternative splicing fingerprints in the TGFβ pathway.
39.	Li, He, et al. (författare) Identification of a Sjögren's syndrome susceptibility locus at OAS1 that influences isoform switching, protein expression, and responsiveness to type I interferons 2017 Ingår i: PLOS Genetics. - : PUBLIC LIBRARY SCIENCE. - 1553-7390 .- 1553-7404. ; 13:6 Tidskriftsartikel (refereegranskat)abstract Sjogren's syndrome (SS) is a common, autoimmune exocrinopathy distinguished by keratoconjunctivitis sicca and xerostomia. Patients frequently develop serious complications including lymphoma, pulmonary dysfunction, neuropathy, vasculitis, and debilitating fatigue. Dysregulation of type I interferon (IFN) pathway is a prominent feature of SS and is correlated with increased autoantibody titers and disease severity. To identify genetic determinants of IFN pathway dysregulation in SS, we performed cis-expression quantitative trait locus (eQTL) analyses focusing on differentially expressed type I IFN-inducible transcripts identified through a transcriptome profiling study. Multiple cis-eQTLs were associated with transcript levels of 2'-5'-oligoadenylate synthetase 1 (OAS1) peaking at rs10774671 (PeQTL = 6.05 x 10(-14)). Association of rs10774671 with SS susceptibility was identified and confirmed through meta-analysis of two independent cohorts (P-meta = 2.59 x 10(-9); odds ratio = 0.75; 95% confidence interval = 0.66-0.86). The risk allele of rs10774671 shifts splicing of OAS1 from production of the p46 isoform to multiple alternative transcripts, including p42, p48, and p44. We found that the isoforms were differentially expressed within each genotype in controls and patients with and without autoantibodies. Furthermore, our results showed that the three alternatively spliced isoforms lacked translational response to type I IFN stimulation. The p48 and p44 isoforms also had impaired protein expression governed by the 3' end of the transcripts. The SS risk allele of rs10774671 has been shown by others to be associated with reduced OAS1 enzymatic activity and ability to clear viral infections, as well as reduced responsiveness to IFN treatment. Our results establish OAS1 as a risk locus for SS and support a potential role for defective viral clearance due to altered IFN response as a genetic pathophysiological basis of this complex autoimmune disease.
40.	Lind, Ulrika, et al. (författare) Analysis of aquaporins from the euryhaline barnacle Balanus improvisus reveals differential expression in response to changes in salinity 2017 Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:7 Tidskriftsartikel (refereegranskat)abstract Barnacles are sessile macro-invertebrates, found along rocky shores in coastal areas worldwide. The euryhaline bay barnacle Balanus improvisus (Darwin, 1854) (= Amphibalanus improvisus) can tolerate a wide range of salinities, but the molecular mechanisms underlying the osmoregulatory capacity of this truly brackish species are not well understood. Aquaporins are pore-forming integral membrane proteins that facilitate transport of water, small solutes and ions through cellular membranes, and that have been shown to be important for osmoregulation in many organisms. The knowledge of the function of aquaporins in crustaceans is, however, limited and nothing is known about them in barnacles. We here present the repertoire of aquaporins from a thecostracan crustacean, the barnacle B. improvisus, based on genome and transcriptome sequencing. Our analyses reveal that B. improvisus contains eight genes for aquaporins. Phylogenetic analysis showed that they represented members of the classical water aquaporins (Aqp1, Aqp2), the aquaglyceroporins (Glp1, Glp2), the unorthodox aquaporin (Aqp12) and the arthropod-specific big brain aquaporin (Bib). Interestingly, we also found two big brain-like proteins (BibL1 and BibL2) constituting a new group of aquaporins not yet described in arthropods. In addition, we found that the two water-specific aquaporins were expressed as C-terminal splice variants. Heterologous expression of some of the aquaporins followed by functional characterization showed that Aqp1 transported water and Glp2 water and glycerol, agreeing with the predictions of substrate specificity based on 3D modeling and phylogeny. To investigate a possible role for the B. improvisus aquaporins in osmoregulation, mRNA expression changes in adult barnacles were analysed after long-term acclimation to different salinities. The most pronounced expression difference was seen for AQP1 with a substantial (>100-fold) decrease in the mantle tissue in low salinity (3 PSU) compared to high salinity (33 PSU). Our study provides a base for future mechanistic studies on the role of aquaporins in osmoregulation. © 2017 Lind et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
41.	Lindvall, Björn, 1952-, et al. (författare) Subclinical myositis is common in primary Sjögren's syndrome and is not related to muscle pain 2002 Ingår i: Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 29:4, s. 717-725 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: Although muscle pain is common in primary Sjögren's syndrome (SS), the underlying mechanisms are mainly unknown. We studied all patients with SS at our rheumatology unit with respect to muscle pain in general and to fibromyalgia (FM), and correlated clinical data to muscle biopsy findings.METHODS: We investigated 48 patients with SS according to the modified European diagnostic criteria. The ACR criteria for FM were used to subgroup the patients. Muscle biopsy was performed in 36 patients. Light microscope morphology and immunohistochemical expression of MHC class I, MHC class II, and membrane attack complex (MAC) were studied.RESULTS: We found 44% of patients complained of muscle pain; 27% fulfilled the ACR criteria for FM, whereas 17% had other forms of myalgia. Muscle pain could not be related to histopathological findings. Signs of inflammation were found in 26 of 36 biopsies (72%), and inflammation combined with degeneration/regeneration (i.e., histological signs of polymyositis) in 17 biopsies (47%). However, only 5 patients (14%) had clinical as well as histological signs of polymyositis. Eight muscle biopsies (22%) showed histological features of inclusion body myositis (IBM). However, no patient had clinical symptoms suggestive of this disease. Abnormal expression of MHC class I, MHC class II, and MAC was found in 18 (50%), 16 (44%), and 27 (75%) patients, respectively.CONCLUSION: Muscle pain, especially FM, is common in SS. Histopathological signs of myositis are very common in SS. However, muscle symptoms are not related to histological signs of muscle inflammation. IBM-like findings may represent vacuolar myopathic degeneration due to previous subclinical muscle inflammation rather than a specific clinical entity.
42.	Liu, Ke, et al. (författare) X Chromosome Dose and Sex Bias in Autoimmune Diseases 2016 Ingår i: Arthritis & Rheumatology. - : WILEY-BLACKWELL. - 2326-5191 .- 2326-5205. ; 68:5, s. 1290-1300 Tidskriftsartikel (refereegranskat)abstract Objective. More than 80% of autoimmune disease predominantly affects females, but the mechanism for this female bias is poorly understood. We suspected that an X chromosome dose effect accounts for this, and we undertook this study to test our hypothesis that trisomy X (47, XXX; occurring in similar to 1 in 1,000 live female births) would be increased in patients with female-predominant diseases (systemic lupus erythematosus [SLE], primary Sjogrens syndrome [SS], primary biliary cirrhosis, and rheumatoid arthritis [RA]) compared to patients with diseases without female predominance (sarcoidosis) and compared to controls. Methods. All subjects in this study were female. We identified subjects with 47, XXX using aggregate data from single-nucleotide polymorphism arrays, and, when possible, we confirmed the presence of 47, XXX using fluorescence in situ hybridization or quantitative polymerase chain reaction. Results. We found 47, XXX in 7 of 2,826 SLE patients and in 3 of 1,033 SS patients, but in only 2 of 7,074 controls (odds ratio in the SLE and primary SS groups 8.78 [95% confidence interval 1.67-86.79], P = 0.003 and odds ratio 10.29 [95% confidence interval 1.18-123.47], P = 0.02, respectively). One in 404 women with SLE and 1 in 344 women with SS had 47, XXX. There was an excess of 47, XXX among SLE and SS patients. Conclusion. The estimated prevalence of SLE and SS in women with 47, XXX was similar to 2.5 and similar to 2.9 times higher, respectively, than that in women with 46, XX and similar to 25 and similar to 41 times higher, respectively, than that in men with 46, XY. No statistically significant increase of 47, XXX was observed in other female-biased diseases (primary biliary cirrhosis or RA), supporting the idea of multiple pathways to sex bias in autoimmunity.
43.	Mandalenakis, Zacharias, 1979, et al. (författare) Atrial Fibrillation Burden in Young Patients with Congenital Heart Disease. 2018 Ingår i: Circulation. - 1524-4539. ; 137:9, s. 928-937 Tidskriftsartikel (refereegranskat)abstract Background -Patients with congenital heart disease (CHD) are assumed to be vulnerable to atrial fibrillation (AF) due to residual shunts, anomalous vessel anatomy, progressive valvulopathy, hypertension, and atrial scars from previous heart surgery. However, the risk of developing AF as well as the complications associated with AF in children and young adults with CHD have not been compared with those in controls. Methods -Data from the Swedish Patient and Cause of Death Registers were used to identify all patients with a diagnosis of CHD who were born from 1970 to 1993. Each patient with CHD was matched by birth year, sex, and county with 10 controls from the Total Population Register in Sweden. Follow-up data were collected until 2011. Results -Among 21,982 patients (51.6% men) with CHD and 219,816 matched controls, 654 and 328 developed AF, respectively. The mean follow-up was 27 years. The risk of developing AF was 21.99 times higher (95% confidence interval, 19.26-25.12) in patients with CHD than controls. According to a hierarchic CHD classification, patients with conotruncal defects had the highest risk (hazard ratio, 84.27; 95% confidence interval, 56.86-124.89). At the age of 42 years, 8.3% of all patients with CHD had a recorded diagnosis of AF. Heart failure was the quantitatively most important complication in patients with CHD and AF, with a 10.7% (70/654) recorded diagnosis of heart failure. Conclusions -The risk of AF in children and young adults with CHD was 22 times higher than that in matched controls. Up to the age of 42 years, 1 of 12 patients with CHD had developed AF and 1 of 10 patients with CHD with AF had developed heart failure. The patient groups with the most complex congenital defects carried the greatest risk of AF and could be considered for targeted monitoring.
44.	Mandalenakis, Zacharias, 1979, et al. (författare) Atrial natriuretic peptide as a predictor of atrial fibrillation in a male population study. The Study of Men Born in 1913 and 1923 2014 Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 171:1, s. 44-48 Tidskriftsartikel (refereegranskat)abstract Background: Atrial fibrillation is one of the most common arrhythmias in clinical practice and it is often diagnosed after a complication occurs. The study aimed to evaluate the predictive value of atrial natriuretic peptide (ANP) for atrial fibrillation in a male population-based study. Methods and results: This study is a part of the "Study of Men Born in 1913 and 1923", a longitudinal prospective cohort study of men, living in the city of Gothenburg in Sweden. A population-based sample of 528 men was investigated in 1988 when they were aged 65 years (n = 134) and 75 years (n = 394), and they were followed up for 16 years. Blood samples were collected from all 528 men at baseline and plasma ANP levels were analyzed by radioimmunoassay. Hazard ratios were estimated by competing-risk regression analysis. One hundred five participants were excluded because of a prior diagnosis of atrial fibrillation, congestive heart failure, severe hypertension, or severe chronic renal insufficiency. Of the remaining 423 participants, 90 men were diagnosed with atrial fibrillation over the 16-year follow-up. In multivariable analysis, men in the two highest quartiles of ANP levels had a significantly higher risk for atrial fibrillation compared with men in the lowest ANP quartile. The adjusted ratio was 3.14 (95% CI 1.59-6.20) for the third ANP quartile and 3.36 (95% CI 1.72-6.54) for the highest quartile of ANP level. Conclusions: In this population-based longitudinal study, we found that elevated ANP levels at baseline predicted atrial fibrillation during a follow-up time of 16 years.
45.	Mandalenakis, Zacharias, 1979, et al. (författare) Ischemic Stroke in Children and Young Adults With Congenital Heart Disease 2016 Ingår i: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 5:2 Tidskriftsartikel (refereegranskat)abstract Background-Patients with congenital heart disease (CHD) may be at increased risk of ischemic stroke due to residual shunts, arrhythmias, and other cardiovascular abnormalities. We studied the relative risk and potential factors for developing ischemic stroke in children and young adults with CHD in Sweden. Methods and Results-All patients in the Swedish Patient Register with a diagnosis of CHD, born between 1970 and 1993, were identified and compared with 10 controls for each patient, matched for age, sex, and county and randomly selected from the general population. Follow-up data through 2011 were collected for both groups. Of 25 985 children and young adults with CHD (51.5% male, 48.5% female), 140 (0.5%) developed ischemic stroke. The hazard ratio for CHD patients developing ischemic stroke was 10.8 (95% CI, 8.5-13.6) versus controls. All major Marelli groups had significantly increased risk, but because of small CHD-group sizes, only atrial septal defect/patent foramen ovale, double-inlet ventricle, and aortic coarctation displayed significantly increased risk. In multivariate analysis of CHD patients, congestive heart failure carried the highest risk for developing ischemic stroke (hazard ratio 6.9 [95% CI, 4.7-10.3]), followed by hypertension and atrial fibrillation, which were also significantly associated with increased risk of ischemic stroke. Conclusions-The risk of developing ischemic stroke was almost 11 times higher in young patients with CHD than in the general population, although absolute risk is low. Cardiovascular comorbidities were strongly associated with the development of ischemic stroke in young CHD patients.
46.	Mandalenakis, Zacharias, 1979, et al. (författare) The risk of atrial fibrillation in the general male population: a lifetime follow-up of 50-year-old men 2015 Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 17:7, s. 1018-1022 Tidskriftsartikel (refereegranskat)abstract Aim This study aimed to estimate the prevalence, incidence rate, and lifetime risk of developing atrial fibrillation (AF) in a population-based study of Swedish men. Methods and results The study is a part of 'The Study of Men Born in 1913', which is a longitudinal prospective cohort study of 855 men born in 1913 and living in the city of Gothenburg in Sweden. They were followed from the age of 50 years until 98 years with repeated examinations and data from the Swedish National Hospital Discharge Register. A total of 185 (21.6%) men developed AF. The prevalence of AF increased from 0.4% at 50 years old, to 1.9% by 60 years old, to 4.6% by 70 years old, to 12.5% by 80 years old, and to 15.7% by 90 years old. The lifetime risk of developing AF was 22.5%. Conclusion Atrial fibrillation is rare at the age of 50 in Swedish men, but it increases exponentially with age, markedly accelerating after 70 years old. In nonagenarians, one of five men has or has had AF.
47.	Martinsson, Klara, et al. (författare) Elevated free secretory component in early rheumatoid arthritis and prior to arthritis development in patients at increased risk 2020 Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 59:5, s. 979-987 Tidskriftsartikel (refereegranskat)abstract Objectives. Considering growing evidence of mucosal involvement in RA induction, this study investigated circulating free secretory component (SC) in patients with either recent-onset RA or with ACPA and musculoskeletal pain. Methods. Two prospective cohorts were studied: TIRA-2 comprising 452 recent-onset RA patients with 3 years of clinical and radiological follow-up, and TIRx patients (n = 104) with ACPA IgG and musculoskeletal pain followed for 290 weeks (median). Blood donors and three different chronic inflammatory diseases served as controls. Free SC was analysed by sandwich ELISA. Results. Serum levels of free SC were significantly higher in TIRA-2 patients compared with TIRx and all control groups (P < 0.01). Among TIRx patients who subsequently developed arthritis, free SC levels were higher compared with all control groups (P < 0.05) except ankylosing spondylitis (P = 0.74). In TIRA-2, patients with ACPA had higher baseline levels of free SC compared with ACPA negative patients (P < 0.001). Free SC status at baseline did not predict radiographic joint damage or disease activity over time. In TIRx, elevated free SC at baseline trendwise associated with arthritis development during follow-up (P = 0.066) but this disappeared when adjusting for confounders (P = 0.72). Cigarette smoking was associated with higher levels of free SC in both cohorts. Conclusion. Serum free SC levels are increased in recent-onset RA compared with other inflammatory diseases, and associate with ACPA and smoking. Free SC is elevated before arthritis development among ACPA positive patients with musculoskeletal pain, but does not predict arthritis development. These findings support mucosal engagement in RA development.
48.	Mofors, Johannes, et al. (författare) Increased risk of multiple myeloma in primary Sjogrens syndrome is limited to individuals with Ro/SSA and La/SSB autoantibodies 2020 Ingår i: Annals of the Rheumatic Diseases. - : BMJ PUBLISHING GROUP. - 0003-4967 .- 1468-2060. ; 79:2, s. 307-308 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract n/a
49.	Nordin, Jessika, et al. (författare) Association of Protective HLA-A With HLA-B∗27 Positive Ankylosing Spondylitis 2021 Ingår i: Frontiers in Genetics. - Lausanne, Switzerland : Frontiers Media S.A.. - 1664-8021. ; 12 Tidskriftsartikel (refereegranskat)abstract Objectives: To further elucidate the role of the MHC in ankylosing spondylitis by typing 17 genes, searching for HLA-B∗27 independent associations and assessing the impact of sex on this male biased disease.Methods: High-confidence two-field resolution genotyping was performed on 310 cases and 2196 controls using an n-1 concordance method. Protein-coding variants were called from next-generation sequencing reads using up to four software programs and the consensus result recorded. Logistic regression tests were applied to the dataset as a whole, and also in stratified sets based on sex or HLA-B∗27 status. The amino acids driving association were also examined.Results: Twenty-five HLA protein-coding variants were significantly associated to disease in the population. Three novel protective associations were found in a HLA-B∗27 positive population, HLA-A∗24:02 (OR = 0.4, CI = 0.2–0.7), and HLA-A amino acids Leu95 and Gln156. We identified a key set of seven loci that were common to both sexes, and robust to change in sample size. Stratifying by sex uncovered three novel risk variants restricted to the female population (HLA-DQA1∗04.01, -DQB1∗04:02, -DRB1∗08:01; OR = 2.4–3.1). We also uncovered a set of neutral variants in the female population, which in turn conferred strong effects in the male set, highlighting how population composition can lead to the masking of true associations.Conclusion: Population stratification allowed for a nuanced investigation into the tightly linked MHC region, revealing novel HLA-B∗27 signals as well as replicating previous HLA-B∗27 dependent results. This dissection of signals may help to elucidate sex biased disease predisposition and clinical progression.
50.	Nyholm, Tufve, et al. (författare) A national approach for automated collection of standardized and population-based radiation therapy data in Sweden 2016 Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 119:2, s. 344-350 Tidskriftsartikel (refereegranskat)abstract Purpose: To develop an infrastructure for structured and automated collection of interoperable radiation therapy (RT) data into a national clinical quality registry. Materials and methods: The present study was initiated in 2012 with the participation of seven of the 15 hospital departments delivering RT in Sweden. A national RT nomenclature and a database for structured unified storage of RT data at each site (Medical Information Quality Archive, MIQA) have been developed. Aggregated data from the MIQA databases are sent to a national RT registry located on the same IT platform (INCA) as the national clinical cancer registries. Results: The suggested naming convention has to date been integrated into the clinical workflow at 12 of 15 sites, and MIQA is installed at six of these. Involvement of the remaining 3/15 RT departments is ongoing, and they are expected to be part of the infrastructure by 2016. RT data collection from ARIA (R), Mosaiq (R), Eclipse (TM), and Oncentra (R) is supported. Manual curation of RT-structure information is needed for approximately 10% of target volumes, but rarely for normal tissue structures, demonstrating a good compliance to the RT nomenclature. Aggregated dose/volume descriptors are calculated based on the information in MIQA and sent to INCA using a dedicated service (MIQA2INCA). Correct linkage of data for each patient to the clinical cancer registries on the INCA platform is assured by the unique Swedish personal identity number. Conclusions: An infrastructure for structured and automated prospective collection of syntactically inter operable RT data into a national clinical quality registry for RT data is under implementation. Future developments include adapting MIQA to other treatment modalities (e.g. proton therapy and brachytherapy) and finding strategies to harmonize structure delineations. How the RT registry should comply with domain-specific ontologies such as the Radiation Oncology Ontology (ROO) is under discussion.

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