| 1. |
- Hansson, Kristofer, et al.
(author)
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Introduction: Interpreting the brain in society
- 2017
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In: Interpreting the brain in society. Cultural reflections on neuroscientific practices. - 1404-000X. - 9789179242930 - 9789198085495 - 9789179242961 ; , s. 11-15
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Book chapter (peer-reviewed)
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| 2. |
- Bergström, Markus, et al.
(author)
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The Settlement
- 2019
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In: Verksmidjan art space in Hjalteyri, Iceland (Permanent installation) N4 regional television.
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Artistic work (other academic/artistic)abstract
- A one week workshop and performance leading up to a permanent installation of a prototyped, functional living space within a former fish factory. Initiated by french artist Sonia Levy, director of Verksmidjan Gustav Geir Bollason and myself. Carried out in all by 13 participants (stated above).
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| 3. |
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| 4. |
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| 6. |
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| 7. |
- Lindgren, Markus, 1975-
(author)
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Measurement and Simulation Based Techniques for Real-Time Systems Analysis
- 2000
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Licentiate thesis (other academic/artistic)abstract
- Rigorous methods for design and implementation of safety critical real-time systems are vital to avoid loss of human lives and/or severe economic losses. Unfortunately, many of these systems are designed and evaluated using ad-hoc techniques. There are, on the other hand, relatively well developed theories for modeling and analysis of timing and reliability. These theories are, however, seldom applied in industry for system development, mainly because of the simplifying model assumptions and lack of appropriate tool support.This thesis presents two new methods aimed to narrow the gap between research results and industrial practice in evaluation and design of real-time systems.The first contribution is a technique that can be used to derive worst-case execution time estimates for real-time software by measurments on the target system. Such estimates are essential when verifying if a system fulfills its timing requirements. The second contribution is a simulation based technique that can be used to evaluate timing aspects of distributed real-time systems, as well as calculating reliability estimates of these systems. Such estimates are essential in determining if a system meets its requirements sufficiently well. Compared to existing analytical methods for execution time analysis and schedulability analysis, which analyze models of the hardware, the starting point for both these methods are real target systems, rather than an abstract model with limited correspondance to reality.The presented initial case-studies give clear evidence that the proposed methods have potential of being both applicable and useful.
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| 8. |
- Mitchell, Jonathan S., et al.
(author)
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Genome-wide association study identifies multiple susceptibility loci for multiple myeloma
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P = 1.31 x 10(-8)), 6q21 (rs9372120, P = 9.09 x 10(-15)), 7q36.1 (rs7781265, P = 9.71 x 10(-9)), 8q24.21 (rs1948915, P = 4.20 x 10(-11)), 9p21.3 (rs2811710, P = 1.72 x 10(-13)), 10p12.1 (rs2790457, P = 1.77 x 10(-8)), 16q23.1 (rs7193541, P = 5.00 x 10(-12)) and 20q13.13 (rs6066835, P = 1.36 x 10(-13)), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development.
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| 9. |
- Schmidt, Amand F., et al.
(author)
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Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9
- 2019
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In: BMC Cardiovascular Disorders. - : BMC. - 1471-2261 .- 1471-2261. ; 19:1
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Journal article (peer-reviewed)abstract
- Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.
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| 10. |
- Went, Molly, et al.
(author)
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Genetic correlation between multiple myeloma and chronic lymphocytic leukaemia provides evidence for shared aetiology
- 2018
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In: Blood Cancer Journal. - : Springer Science and Business Media LLC. - 2044-5385. ; 9:1
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Journal article (peer-reviewed)abstract
- The clustering of different types of B-cell malignancies in families raises the possibility of shared aetiology. To examine this, we performed cross-trait linkage disequilibrium (LD)-score regression of multiple myeloma (MM) and chronic lymphocytic leukaemia (CLL) genome-wide association study (GWAS) data sets, totalling 11,734 cases and 29,468 controls. A significant genetic correlation between these two B-cell malignancies was shown (Rg = 0.4, P = 0.0046). Furthermore, four of the 45 known CLL risk loci were shown to associate with MM risk and five of the 23 known MM risk loci associate with CLL risk. By integrating eQTL, Hi-C and ChIP-seq data, we show that these pleiotropic risk loci are enriched for B-cell regulatory elements and implicate B-cell developmental genes. These data identify shared biological pathways influencing the development of CLL and, MM and further our understanding of the aetiological basis of these B-cell malignancies.
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| 11. |
- Went, Molly, et al.
(author)
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Transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genes
- 2019
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In: Human Genomics. - : Springer Science and Business Media LLC. - 1479-7364. ; 13:1
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Journal article (peer-reviewed)abstract
- BackgroundWhile genome-wide association studies (GWAS) of multiple myeloma (MM) have identified variants at 23 regions influencing risk, the genes underlying these associations are largely unknown. To identify candidate causal genes at these regions and search for novel risk regions, we performed a multi-tissue transcriptome-wide association study (TWAS).ResultsGWAS data on 7319 MM cases and 234,385 controls was integrated with Genotype-Tissue Expression Project (GTEx) data assayed in 48 tissues (sample sizes, N = 80–491), including lymphocyte cell lines and whole blood, to predict gene expression. We identified 108 genes at 13 independent regions associated with MM risk, all of which were in 1 Mb of known MM GWAS risk variants. Of these, 94 genes, located in eight regions, had not previously been considered as a candidate gene for that locus.ConclusionsOur findings highlight the value of leveraging expression data from multiple tissues to identify candidate genes responsible for GWAS associations which provide insight into MM tumorigenesis. Among the genes identified, a number have plausible roles in MM biology, notably APOBEC3C, APOBEC3H, APOBEC3D, APOBEC3F, APOBEC3G, or have been previously implicated in other malignancies. The genes identified in this TWAS can be explored for follow-up and validation to further understand their role in MM biology.
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| 12. |
- Abildgaard, Niels, et al.
(author)
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Real-world treatment patterns and outcomes for patients with multiple myeloma in Denmark, Finland and Sweden : An analysis using linked Nordic registries
- 2024
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In: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 201
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Journal article (peer-reviewed)abstract
- Aim: The Health outcomes and Understanding of MyelomA multi-National Study (HUMANS) was a large-scale, retrospective study conducted across Denmark, Finland and Sweden using linked data from national registries. We describe the characteristics, treatment patterns and clinical outcomes for patients with newly diagnosed multiple myeloma (NDMM) over 2010–2018.Methods: Patients with NDMM who received MM-specific, first-line treatments, were categorised by treatment (autologous stem cell transplantation [ASCT] or a combination chemotherapy regimen based on bortezomib, lenalidomide or melphalan-prednisolone-thalidomide).Results: 11,023 patients received treatment over 2010–2018. Time between diagnosis and treatment was shortest in Denmark (0.9 months), then Sweden (2.9 months) and Finland (4.6 months). Around one third of patients underwent ASCT. Lenalidomide-based regimens were prescribed to 23–28% of patients in Denmark and Finland, versus 12% in Sweden. Patients receiving lenalidomide had the longest wait for treatment, from 3.2 months (Denmark) to 12.1 months (Sweden). Treatment persistence was highest among patients receiving melphalan-prednisolone-thalidomide (7–8 months) in Finland and Sweden and lowest among those receiving bortezomib (3.5 months) in Finland. Overall survival (OS) was longest among patients with ASCT (7–10 years). Among patients receiving chemotherapy, OS (from diagnosis/treatment initiation), varied between cohorts. In a sensitivity analysis excluding patients with smouldering MM, OS decreased for all; for patients receiving bortezomib or lenalidomide, OS from diagnosis was 40–49 and 27–54 months, respectively.Conclusions: This population-based study of patients with NDMM receiving first-line MM-specific treatment, provides real-world data on treatment patterns and outcomes to complement data from randomised clinical trials.
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| 13. |
- Abildgaard, Niels, et al.
(author)
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Use of Linked Nordic Registries for Population Studies in Hematologic Cancers: The Case of Multiple Myeloma
- 2023
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In: Clinical Epidemiology. - : Dove Medical Press. - 1179-1349. ; 15, s. 987-999
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Journal article (peer-reviewed)abstract
- Purpose: Linked health-care registries and high coverage in Nordic countries lend themselves well to epidemiologic research. Given its relatively high incidence in Western Europe, complexity in diagnosis, and challenges in registration, multiple myeloma (MM) wasselected to compare registries in Denmark, Finland, and Sweden.Patients and Methods: Data were obtained from four archetypal registries in each country (spanning January 2005–October 2018):National Patient Registry (NPR), Prescribed Drug Registry (PDR), Cancer Registry (CR), and Cause of Death Registry. Patients newlydiagnosed with MM who received MM-specific treatment were included. PDR/NPR treatment records were used to assess incidentNPR cases. The registration quality of MM-specific drugs in the PDR of each country was also evaluated.Results: In Denmark, only 6% of patients in the NPR were not registered in the CR; in Sweden, it was 16.9%. No systematicdifferences were identified that could explain this discrepancy. In Denmark, lenalidomide and bortezomib were registered in the NPRwith high coverage, but less expensive drugs typically given in combination with bortezomib were not covered in any of the registries.In Finland and Sweden, bortezomib records were not identified in the PDR, but some were in the NPR; other drugs had good coveragein the PDR.Conclusions: The registries evaluated in this study can be used to identify the MM population; however, given the gaps in MMregistration in the Finnish and Swedish CRs, Danish registries provide the most comprehensive datasets for research on treatmentpatterns for MM.
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| 14. |
- Ahlén Bergman, Emma, et al.
(author)
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Increased CD4+ T cell lineage commitment determined by CpG methylation correlates with better prognosis in urinary bladder cancer patients
- 2018
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In: Clinical Epigenetics. - : BMC. - 1868-7083 .- 1868-7075. ; 10
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Journal article (peer-reviewed)abstract
- BACKGROUND: Urinary bladder cancer is a common malignancy worldwide. Environmental factors and chronic inflammation are correlated with the disease risk. Diagnosis is performed by transurethral resection of the bladder, and patients with muscle invasive disease preferably proceed to radical cystectomy, with or without neoadjuvant chemotherapy. The anti-tumour immune responses, known to be initiated in the tumour and draining lymph nodes, may play a major role in future treatment strategies. Thus, increasing the knowledge of tumour-associated immunological processes is important. Activated CD4+ T cells differentiate into four main separate lineages: Th1, Th2, Th17 and Treg, and they are recognized by their effector molecules IFN-γ, IL-13, IL-17A, and the transcription factor Foxp3, respectively. We have previously demonstrated signature CpG sites predictive for lineage commitment of these four major CD4+ T cell lineages. Here, we investigate the lineage commitment specifically in tumour, lymph nodes and blood and relate them to the disease stage and response to neoadjuvant chemotherapy.RESULTS: Blood, tumour and regional lymph nodes were obtained from patients at time of transurethral resection of the bladder and at radical cystectomy. Tumour-infiltrating CD4+ lymphocytes were significantly hypomethylated in all four investigated lineage loci compared to CD4+ lymphocytes in lymph nodes and blood (lymph nodes vs tumour-infiltrating lymphocytes: IFNG -4229 bp p < 0.0001, IL13 -11 bp p < 0.05, IL17A -122 bp p < 0.01 and FOXP3 -77 bp p > 0.05). Examination of individual lymph nodes displayed different methylation signatures, suggesting possible correlation with future survival. More advanced post-cystectomy tumour stages correlated significantly with increased methylation at the IFNG -4229 bp locus. Patients with complete response to neoadjuvant chemotherapy displayed significant hypomethylation in CD4+ T cells for all four investigated loci, most prominently in IFNG p < 0.0001. Neoadjuvant chemotherapy seemed to result in a relocation of Th1-committed CD4+ T cells from blood, presumably to the tumour, indicated by shifts in the methylation patterns, whereas no such shifts were seen for lineages corresponding to IL13, IL17A and FOXP3.CONCLUSION: Increased lineage commitment in CD4+ T cells, as determined by demethylation in predictive CpG sites, is associated with lower post-cystectomy tumour stage, complete response to neoadjuvant chemotherapy and overall better outcome, suggesting epigenetic profiling of CD4+ T cell lineages as a useful readout for clinical staging.
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| 15. |
- Ahmadi, Khazar, et al.
(author)
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Fixel-Based Analysis Reveals Tau-Related White Matter Changes in Early Stages of Alzheimer’s Disease
- 2024
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In: Journal of Neuroscience. - 0270-6474. ; 44:18
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Journal article (peer-reviewed)abstract
- Several studies have shown white matter (WM) abnormalities in Alzheimer’s disease (AD) using diffusion tensor imaging (DTI). Nonetheless, robust characterization of WM changes has been challenging due to the methodological limitations of DTI. We applied fixel-based analyses (FBA) to examine microscopic differences in fiber density (FD) and macroscopic changes in fiber cross-section (FC) in early stages of AD (N = 393, 212 females). FBA was also compared with DTI, free-water corrected (FW)-DTI and diffusion kurtosis imaging (DKI). We further investigated the correlation of FBA and tensor-derived metrics with AD pathology and cognition. FBA metrics were decreased in the entire cingulum bundle, uncinate fasciculus and anterior thalamic radiations in Aβ-positive patients with mild cognitive impairment compared to control groups. Metrics derived from DKI, and FW-DTI showed similar alterations whereas WM degeneration detected by DTI was more widespread. Tau-PET uptake in medial temporal regions was only correlated with reduced FC mainly in the parahippocampal cingulum in Aβ-positive individuals. This tau-related WM alteration was also associated with impaired memory. Despite the spatially extensive between-group differences in DTI-metrics, the link between WM and tau aggregation was only revealed using FBA metrics implying high sensitivity but low specificity of DTI-based measures in identifying subtle tau-related WM degeneration. No relationship was found between amyloid load and any diffusion-MRI measures. Our results indicate that early tau-related WM alterations in AD are due to macrostructural changes specifically captured by FBA metrics. Thus, future studies assessing the effects of AD pathology in WM tracts should consider using FBA metrics.
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| 16. |
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| 17. |
- Akhoondi, Shahab, et al.
(author)
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FBXW7/hCDC4 is a general tumor suppressor in human cancer
- 2007
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In: Cancer Research. - 0008-5472 .- 1538-7445. ; 67:19, s. 9006-9012
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Journal article (peer-reviewed)abstract
- The ubiquitin-proteasome system is a major regulatory pathway of protein degradation and plays an important role in cellular division. Fbxw7 (or hCdc4), a member of the F-box family of proteins, which are substrate recognition components of the multisubunit ubiquitin ligase SCF (Skpl-Cdc53/ Cullin-F-box-protein), has been shown to mediate the ubiquitin-dependent proteolysis of several oncoproteins including cyclin El, c-Myc, c-Jun, and Notch. The oncogenic potential of Fbxw7 substrates, frequent allelic loss in human cancers, and demonstration that mutation of FBXW7 cooperates with p53 in mouse tumorigenesis have suggested that Fbxw7 could function as a tumor suppressor in human cancer. Here, we carry out an extensive genetic screen of primary tumors to evaluate the role of FBXW7 as a tumor suppressor in human tumorigenesis. Our results indicate that FBXW7 is inactivated by mutation in diverse human cancer types with an overall mutation frequency of ∼ 6%. The highest mutation frequencies were found in tumors of the bile duct (cholangio-carcinomas, 35%), blood (T-cell acute lymphocytic leukemia, 31%), endometrium (9%), colon (9%), and stomach (6%). Approximately 43% of all mutations occur at two mutational "hotspots," which alter Arg residues (Arg465 and Arg479) that are critical for substrate recognition. Furthermore, we show that Fbxw7Arg465 hotspot mutant can abrogate wild-type Fbxw7 function through a dominant negative mechanism. Our study is the first comprehensive screen of FBXW7 mutations in various human malignancies and shows that FBXW7 is a general tumor suppressor in human cancer.
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- Ali, Mina, et al.
(author)
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The multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression
- 2018
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 1649-
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Journal article (peer-reviewed)abstract
- Recently, we identified ELL2 as a susceptibility gene for multiple myeloma (MM). To understand its mechanism of action, we performed expression quantitative trait locus analysis in CD138+ plasma cells from 1630 MM patients from four populations. We show that the MM risk allele lowers ELL2 expression in these cells (Pcombined = 2.5 × 10−27; βcombined = −0.24 SD), but not in peripheral blood or other tissues. Consistent with this, several variants representing the MM risk allele map to regulatory genomic regions, and three yield reduced transcriptional activity in plasmocytoma cell lines. One of these (rs3777189-C) co-locates with the best-supported lead variants for ELL2 expression and MM risk, and reduces binding of MAFF/G/K family transcription factors. Moreover, further analysis reveals that the MM risk allele associates with upregulation of gene sets related to ribosome biogenesis, and knockout/knockdown and rescue experiments in plasmocytoma cell lines support a cause–effect relationship. Our results provide mechanistic insight into MM predisposition.
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| 22. |
- Andersson, Emelie, et al.
(author)
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Blood and cerebrospinal fluid neurofilament light differentially detect neurodegeneration in early Alzheimer's disease
- 2020
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In: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 95, s. 143-153
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Journal article (peer-reviewed)abstract
- Cerebrospinal fluid (CSF) neurofilament light (NfL) concentration has reproducibly been shown to reflect neurodegeneration in brain disorders, including Alzheimer's disease (AD). NfL concentration in blood correlates with the corresponding CSF levels, but few studies have directly compared the reliability of these 2 markers in sporadic AD. Herein, we measured plasma and CSF concentrations of NfL in 478 cognitively unimpaired (CU) subjects, 227 patients with mild cognitive impairment, and 113 patients with AD dementia. We found that the concentration of NfL in CSF, but not in plasma, was increased in response to Aβ pathology in CU subjects. Both CSF and plasma NfL concentrations were increased in patients with mild cognitive impairment and AD dementia. Furthermore, only NfL in CSF was associated with reduced white matter microstructure in CU subjects. Finally, in a transgenic mouse model of AD, CSF NfL increased before serum NfL in response to the development of Aβ pathology. In conclusion, NfL in CSF may be a more reliable biomarker of neurodegeneration than NfL in blood in preclinical sporadic AD.
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| 23. |
- Andersson, Markus, 1981, et al.
(author)
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Vinylimidazole copolymers: coordination chemistry, solubility, and cross-linking as function of Cu2+ and Zn2+ complexation
- 2011
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In: Colloid and Polymer Science. - : Springer Science and Business Media LLC. - 0303-402X .- 1435-1536. ; 289:12, s. 1361-1372
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Journal article (peer-reviewed)abstract
- P(1-VIm-co-MMA) copolymers with 4 or 44 wt.% 1-VIm (abbreviated PVM-4 and PVM-44) where polymerized from 1-VIm (1-vinylimidazole) and methylmethacrylate with azobisisobutyronitrile as initiator and reacted with either Cu(2+) or Zn(2+). The resulting coordinated polymer complexes were studied using ICP-AES, CP/MAS (13)C NMR, conductivity measurements, vibrational spectroscopy (mid-FTIR and far-FTIR), DSC, and EPR. It was established by ICP-AES, CP/MAS (13)C NMR, conductivity, mid-FTIR and EPR measurements that the transition metal ions in the complexes were exclusively coordinated by the imidazole ligand. The coordination geometry is square planar with regard to Cu(II) complexes. The strong interaction between the polymeric imidazole ligand and the transition metal ion cross-links the system, resulting in augmentation of T (g) (the glass transition temperature), especially for copolymers with high relative amount of 1-VIm. The effect of changing metal ion is more complicated and depends on both the strength of the coordinate interaction as well as the coordination number. The solubility of the coordinate polymer complex in conventional solvents is low due to the coordinate cross-links. However, the coordinate polymer complexes are soluble in strongly coordinating solvents such as acetonitrile and dimethylsulfoxide.
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| 24. |
- Ashton, Nicholas J., et al.
(author)
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A multicentre validation study of the diagnostic value of plasma neurofilament light
- 2021
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12, s. 1-12
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Journal article (peer-reviewed)abstract
- Increased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can also be assessed in blood. Here, we investigate plasma NfL as a marker of neurodegeneration in 13 neurodegenerative disorders, Down syndrome, depression and cognitively unimpaired controls from two multicenter cohorts: King's College London (n = 805) and the Swedish BioFINDER study (n = 1,464). Plasma NfL was significantly increased in all cortical neurodegenerative disorders, amyotrophic lateral sclerosis and atypical parkinsonian disorders. We demonstrate that plasma NfL is clinically useful in identifying atypical parkinsonian disorders in patients with parkinsonism, dementia in individuals with Down syndrome, dementia among psychiatric disorders, and frontotemporal dementia in patients with cognitive impairment. Data-driven cut-offs highlighted the fundamental importance of age-related clinical cut-offs for disorders with a younger age of onset. Finally, plasma NfL performs best when applied to indicate no underlying neurodegeneration, with low false positives, in all age-related cut-offs.
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| 25. |
- Askman, Sandra, et al.
(author)
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Decreased neutrophil function in newly diagnosed multiple myeloma patients is restored with lenalidomide therapy
- 2024
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In: EUROPEAN JOURNAL OF HAEMATOLOGY. - 0902-4441 .- 1600-0609.
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Journal article (peer-reviewed)abstract
- ObjectivesBacterial infections are common and a major cause of morbidity and mortality in multiple myeloma (MM). We have investigated the function of polymorphonuclear leukocyte (PMN), the immune system's first line of defense against bacteria, in peripheral blood (PB) and bone marrow (BM) samples from patients with newly diagnosed MM (NDMM), smoldering MM (SMM), monoclonal gammopathy of undetermined significance (MGUS) and healthy controls.MethodsPhagocytosis and oxidative burst in PMN cells from patients and healthy donors were investigated using PhagoTest and PhagoBurst assay.ResultsPMN from NDMM, SMM, and MGUS patients had reduced phagocytosis and oxidative burst ability compared with healthy controls. The dysfunction was most prominent in BM samples from MM, SMM, and MGUS patients. Importantly the reduced phagocytosis in MM patients was restored in patients on lenalidomide therapy. Consistently the ability of Escherichia coli stimulated oxidative burst in BM was reduced for the MM, SMM, and MGUS cohort in contrast to the healthy controls and the patients on lenalidomide treatment.ConclusionOur results show that MM patients have neutrophil dysfunction that could contribute to susceptibility for bacterial infections and that lenalidomide therapy was associated with restored PMN function.
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| 26. |
- Aurelius, Johan, 1980, et al.
(author)
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Monocytic AML cells inactivate antileukemic lymphocytes: role of NADPH oxidase/gp91(phox) expression and the PARP-1/PAR pathway of apoptosis.
- 2012
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In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 119:24, s. 5832-7
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Journal article (peer-reviewed)abstract
- Dysfunction of T cells and natural killer (NK) cells has been proposed to determine the course of disease in acute myeloid leukemia (AML), but only limited information is available on the mechanisms of lymphocyte inhibition. We aimed to evaluate to what extent human malignant AML cells use NADPH oxidase-derived reactive oxygen species (ROS) as an immune evasion strategy. We report that a subset of malignant myelomonocytic and monocytic AML cells (French-American-British [FAB] classes M4 and M5, respectively), recovered from blood or BM of untreated AML patients at diagnosis, expressed the NADPH oxidase component gp91(phox). Highly purified FAB M4/M5 AML cells produced large amounts of ROS on activation and triggered poly-[ADP-ribose] polymerase-1-dependent apoptosis in adjacent NK cells, CD4(+) T cells, and CD8(+) T cells. In contrast, immature (FAB class M1) and myeloblastic (FAB class M2) AML cells rarely expressed gp91(phox), did not produce ROS, and did not trigger NK or T-cell apoptosis. Microarray data from 207 AML patients confirmed a greater expression of gp91(phox) mRNA by FAB-M4/M5 AML cells than FAB-M1 cells (P < 10(-11)) or FAB-M2 cells (P < 10(-9)). Our data are suggestive of a novel mechanism by which monocytic AML cells evade cell-mediated immunity.
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| 27. |
- Aurelius, Johan, 1980, et al.
(author)
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NOX2-dependent immunosuppression in chronic myelomonocytic leukemia
- 2017
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In: Journal of Leukocyte Biology. - 0741-5400 .- 1938-3673. ; 102:2, s. 459-466
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Journal article (peer-reviewed)abstract
- Chronic myelomonocytic leukemia (CMML) is a myeloproliferative and myelodysplastic neoplasm with few treatment options and dismal prognosis. The role of natural killer (NK) cells and other antileukemic lymphocytes in CMML is largely unknown. We aimed to provide insight into the mechanisms of immune evasion in CMML with a focus on immunosuppressive reactive oxygen species (ROS) formed by the myeloid cell NADPH oxidase-2 (NOX2). The dominant population of primary human CMML cells was found to express membrane-bound NOX2 and to release ROS, which, in turn, triggered extensive PARP-1-dependent cell death in cocultured NK cells, CD8(+) T effector memory cells, and CD8(+) T effector cells. Inhibitors of ROS formation and scavengers of extracellular ROS prevented CMML cell-induced lymphocyte death and facilitated NK cell degranulation toward Ab-coated, primary CMML cells. In patients with CMML, elevation of immature cell counts (CD34(+)) in blood was associated with reduced expression of several NK cell-activating receptors. We propose that CMML cells may use extracellular ROS as a targetable mechanism of immune escape.
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| 28. |
- Aurelius, Johan, 1980, et al.
(author)
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Remission maintenance in acute myeloid leukemia: impact of functional histamine H-2 receptors expressed by leukemic cells
- 2012
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In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 97:12, s. 1904-1908
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Journal article (peer-reviewed)abstract
- Post-consolidation immunotherapy with histamine dihydrochloride and interleukin-2 has been shown to improve leukemia-free survival in acute myeloid leukemia in a phase III trial. For this study, treatment efficacy was determined among 145 trial patients with morphological forms of acute myeloid leukemia as defined by the French-American-British classification. Leukemia-free survival was strongly improved in M4/M5 (myelomonocytic/monocytic) leukemia but not in M2 (myeloblastic) leukemia. We also analyzed histamine H-2 receptor expression by leukemic cells recovered from 26 newly diagnosed patients. H-2 receptors were typically absent from M2 cells but frequently expressed by M4/M5 cells. M4/M5 cells, but not M2 cells, produced reactive oxygen species that triggered apoptosis in adjacent natural killer cells. These events were significantly inhibited by histamine dihydrochloride. Our data demonstrate the presence of functional histamine H2 receptors on human AML cells and suggest that expression of these receptors by leukemic cells may impact on the effectiveness of histamine-based immunotherapy.
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| 29. |
- Bengtsen, Peter, et al.
(author)
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Pathological creativity : How popular media connect neurological disease and creative practices
- 2017
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In: Interpreting the brain in society. Cultural reflections on neuroscientific practices. - 1404-000X. - 9789179242930 - 9789198085495 - 9789179242961 ; 25, s. 29-47
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Book chapter (peer-reviewed)abstract
- Book chapter about the linking that is often made in popular media of creativity - frequently through examples from art history - and neurological disease. The chapter discusses the implications this linking may have for the dissemination of ideas about personality traits, artistic expression, neurological disease and neuroscience as a discipline.
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| 30. |
- Bengtsson, Anders, et al.
(author)
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Low production of reactive oxygen species in granulocytes is associated with organ damage in systemic lupus erythematosus
- 2014
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In: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 16:3
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Journal article (peer-reviewed)abstract
- Introduction: Polymorphonuclear leukocytes (PMN) are main effector cells in the acute immune response. While the specific role of PMN in systemic lupus erythematosus (SLE) and autoimmunity is still unclear, their importance in chronic inflammation is gaining more attention. Here we investigate aspects of function, bone marrow release and activation of PMN in patients with SLE. Methods: The following PMN functions and subsets were evaluated using flow cytometry; (a) production of reactive oxygen species (ROS) after ex vivo stimulation with phorbol 12-myristate 13-acetate (PMA) or Escherichia coli (E. coli); (b) capacity to phagocytose antibody-coated necrotic cell material; (c) PMN recently released from bone marrow, defined as percentage of CD10(-)D16(low) in peripheral blood, and (d) PMN activation markers; CD11b, CD62L and C5aR. Results: SLE patients (n = 92) showed lower ROS production compared with healthy controls (n = 38) after activation ex vivo. The ROS production was not associated with corticosteroid dose or other immunotherapies. PMA induced ROS production was significantly reduced in patients with severe disease. In contrast, neither ROS levels after E. coli activation, nor the capacity to phagocytose were associated with disease severity. This suggests that decreased ROS production after PMA activation is a sign of changed PMN behaviour rather than generally impaired functions. The CD10(-)CD16(low) phenotype constitute 2% of PMN in peripheral blood of SLE patients compared with 6.4% in controls, indicating a decreased release of PMN from the bone marrow in SLE. A decreased expression of C5aR on PMN was observed in SLE patients, pointing towards in vivo activation. Conclusions: Our results indicate that PMN from SLE patients have altered function, are partly activated and are released abnormally from bone marrow. The association between low ROS formation in PMN and disease severity is consistent with findings in other autoimmune diseases and might be considered as a risk factor.
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| 31. |
- Bjurbom, Markus, et al.
(author)
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Type A Aortic Dissection Repair in Patients With Prior Cardiac Surgery
- 2023
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In: Annals of Thoracic Surgery. - : Elsevier BV. - 0003-4975 .- 1552-6259. ; 115:3, s. 591-598
-
Journal article (peer-reviewed)abstract
- Background: Emergency surgery for acute type A aortic dissection in patients with previous cardiac surgery is controversial. This study aimed to evaluate the association between previous cardiac surgery and outcomes after surgery for acute type A aortic dissection, to appreciate whether emergency surgery can be offered with acceptable risks. Methods: All patients operated on for acute type A aortic dissection between 2005 and 2014 from the Nordic Consortium for Acute Type A Aortic Dissection database were eligible. Patients with previous cardiac surgery were compared with patients without previous cardiac surgery. Univariable and multivariable statistical analyses were performed to identify predictors of 30-day mortality and early major adverse events (a secondary composite endpoint comprising 30-day mortality, perioperative stroke, postoperative cardiac arrest, or de novo dialysis). Results: In all, 1159 patients were included, 40 (3.5%) with previous cardiac surgery. Patients with previous cardiac surgery had higher 30-day mortality (30% vs 17.8%, P = .049), worse medium-term survival (51.7% vs 71.2% at 5 years, log rank P = .020), and higher unadjusted prevalence of major adverse events (52.5% vs 35.7%, P = .030). In multivariable analysis, previous cardiac surgery was not associated with 30-day mortality (odds ratio 0.78; 95% CI, 0.30-2.07; P = .624) or major adverse events (odds ratio 1.07; 95% CI, 0.45-2.55, P = .879). Conclusions: Major adverse events after surgery for acute type A aortic dissection were more frequent in patients with previous cardiac surgery. Previous cardiac surgery itself was not an independent predictor for adverse events, although the small sample size precludes definite conclusions. Previous cardiac surgery should not deter from emergency surgery.
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| 32. |
- Bjursten, Henrik, et al.
(author)
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Once after a full moon : acute type A aortic dissection and lunar phases
- 2022
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In: Interactive Cardiovascular and Thoracic Surgery. - : Oxford University Press. - 1569-9293 .- 1569-9285. ; 34:1, s. 105-110
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: Acute type A aortic dissection (ATAAD) is a rare but severe condition, routinely treated with emergent cardiac surgery. Many surgeons have the notion that patients with ATAAD tend to come in clusters, but no studies have examined these observations. This investigation was undertaken to study the potential association between the lunar cycle and the incidence of ATAAD.METHODS: We collected information on 2995 patients who underwent ATAAD surgery at centres from the Nordic Consortium for Acute Type A Aortic Dissection collaboration. We cross-referenced the time of surgery with lunar phase using a case-crossover design with 2 different definitions of full moon (>99% illumination and the 7-day full moon period).RESULTS: The period when the moon was illuminated the most (99% definition) did not show any significant increase in incidence for ATAAD surgery. However, when the full moon period was compared with all other moon phases, it yielded a relative risk of 1.08 [95% confidence interval (CI) 1.00-1.17, P = 0.057] and, compared to waxing moon, only the relative risk was 1.11 (95% CI 1.01-1.23, P = 0.027). The peak incidence came 4-6 days after the moon was fully illuminated.CONCLUSIONS: This study found an overrepresentation of surgery for ATAAD during the full moon phase. The explanation for this is not known, but we speculate that sleep deprivation during full moon leads to a temporary increase in blood pressure, which in turn could trigger rupture of the aortic wall. While this finding is interesting, it needs to be corroborated and the clinical implications are debateable.
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| 33. |
- Bjurström, Martin F., et al.
(author)
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Central nervous system monoaminergic activity in hip osteoarthritis patients with disabling pain : associations with pain severity and central sensitization
- 2022
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In: Pain Reports. - 2471-2531. ; 7:1, s. 988-988
-
Journal article (peer-reviewed)abstract
- Introduction: Monoaminergic activity modulates nociceptive transmission in the central nervous system (CNS). Although pain is the most disabling symptom of osteoarthritis (OA), limited knowledge exists regarding the CNS mechanisms that amplify pain and drive sensitization processes in humans.Objectives:The main objective of this study was to evaluate associations between cerebrospinal fluid (CSF) monoamine metabolites, pain severity, and central sensitization in patients with OA undergoing total hip arthroplasty (THA).Methods:Patients with OA (n = 52) and pain-free controls (n = 30) provided CSF samples for measurement of serotonin (5-hydroxyindoleacetic acid [5-HIAA]), noradrenaline (3-methoxy-4-hydroxyphenylglycol [HMPG]), and dopamine (homovanillic acid [HVA]) monoamine metabolites. Patients with OA completed longitudinal evaluation of pain using clinical measures and quantitative sensory testing.Results:Patients with OA had higher HMPG levels when compared with controls (P = 0.036). Within patients with OA undergoing THA, higher 5-HIAA and HVA levels were consistently associated with higher preoperative pain severity. Higher concentrations of 5-HIAA and HVA were also associated with lower conditioned pain modulation levels, whereas higher HMPG levels were linked to more efficient conditioned pain modulation. Patients with higher levels of CSF HVA exhibited increased pressure pain sensitivity (arm pressure pain detection threshold < 250 kPa vs ≥ 250 kPa, P = 0.042). Higher preoperative levels of CSF 5-HIAA predicted poorer pain control 6 months postoperatively (brief pain inventory pain severity; adjusted β = 0.010, 95% CI 0.001-0.019).Conclusions:In OA patients with disabling pain, higher CSF levels of serotonin and dopamine metabolites are associated with increased pain severity and central sensitization. Increased noradrenergic activity may be associated with more efficient pain inhibitory capacity.
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| 34. |
- Björk, Karl, et al.
(author)
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β-Arrestin 2 knockout mice exhibit sensitized dopamine release and increased reward in response to a low dose of alcohol
- 2013
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In: Psychopharmacology. - : Springer. - 0033-3158 .- 1432-2072. ; 230:3, s. 439-449
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Journal article (peer-reviewed)abstract
- RationaleThe rewarding effects of alcohol have been attributed to interactions between opioid and dopaminergic system within the mesolimbic reward pathway. We have previously shown that ablation of β-arrestin 2 (Arrb2), a crucial regulator of μ-opioid receptor function, attenuates alcohol-induced hyperlocomotion and c-fos activation in the nucleus accumbens.ObjectivesHere, we further investigated the role of Arrb2 in modulating alcohol-induced dopamine (DA) release and conditioned place preference (CPP). We also assessed the functional importance of Arrb2 for μ-opioid receptor surface expression and signaling following an acute alcohol challenge.MethodsAlcohol-evoked (0.375, 0.75, and 1.5 g/kg intraperitoneally) DA release was measured by in vivo microdialysis in the shell of nucleus accumbens. Reward was assessed by the CPP paradigm. Receptor function was assessed by μ-receptor binding and [35S]GTP-γ-S autoradiography.ResultsIn Arrb2 knockout mice accumbal DA levels reach maximum response at a lower dose compared to wild-type (wt) animals. In line with these results, Arrb2 knockout mice display increased CPP for alcohol as compared to wt mice. Finally, Arrb2 mutant mice display increased μ-opioid receptor signaling in the ventral and dorsal striatum and amygdala in response to a low dose of alcohol, indicating impaired desensitization mechanisms in these mice.ConclusionsOur results show that Arrb2 modulates the response to low doses of alcohol on various levels including μ-opioid receptor signaling, DA release, and reward. They also reveal a clear dissociation between the effects of Arrb2 on psychomotor and reward behaviors.
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| 35. |
- Blom, Elin S, et al.
(author)
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Increased mRNA Levels of TCF7L2 and MYC of the Wnt Pathway in Tg-ArcSwe Mice and Alzheimer's Disease Brain
- 2010
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In: International journal of Alzheimer's disease. - : Hindawi Limited. - 2090-0252 .- 2090-8024. ; 2011, s. 936580-
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Journal article (peer-reviewed)abstract
- Several components in the Wnt pathway, including β-catenin and glycogen synthase kinase 3 beta, have been implied in AD pathogenesis. Here, mRNA brain levels from five-month-old tg-ArcSwe and nontransgenic mice were compared using Affymetrix microarray analysis. With surprisingly small overall changes, Wnt signaling was the most affected pathway with altered expression of nine genes in tg-ArcSwe mice. When analyzing mRNA levels of these genes in human brain, transcription factor 7-like 2 (TCF7L2) and v-myc myelocytomatosis viral oncogene homolog (MYC), were increased in Alzheimer's disease (AD) (P < .05). Furthermore, no clear differences in TCF7L2 and MYC mRNA were found in brains with frontotemporal lobar degeneration, suggesting that altered regulation of these Wnt-related genes could be specific to AD. Finally, mRNA levels of three neurogenesis markers were analyzed. Increased mRNA levels of dihydropyrimidinase-like 3 were observed in AD brain, suggesting that altered Wnt pathway regulation may signify synaptic rearrangement or neurogenesis.
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| 36. |
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| 37. |
- Borg, Markus, et al.
(author)
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An Analytical View ofTest Results Using CityScapes
- 2018
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Conference paper (other academic/artistic)abstract
- t— In this paper we map test results from a real ASIC project on to the file structure of the design under test andpresent it as a cityscape. In the cityscape each house is a file where its height reflects the number of commits to that file. Thecolor reflects the fraction of bad commits.We identify error prone areas (red "bad" neighborhoods) as well as the most active areas (tall "downtown" areas). Thecityscape also allows us to identify potential test coverage holes (tall green buildings) where there are a lot of activities but nofailures.
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| 38. |
- Borg, Markus, et al.
(author)
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Enabling Visual Design Verification Analytics– From Prototype Visualizations to anAnalytics Tool using the Unity Game Engine
- 2018
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Conference paper (other academic/artistic)abstract
- The ever-increasing architectural complexity in contemporary ASIC projects turns Design Verification (DV)into a highly advanced endeavor. Pressing needs for short time-to-market has made automation a key solution in DV.However, recurring execution of large regression suites inevitably leads to challenging amounts of test results. Following thedesign science paradigm, we present an action research study to introduce visual analytics in a commercial ASIC project. Wedevelop a cityscape visualization tool using the game engine Unity. Initial evaluations are promising, suggesting that the tooloffers a novel approach to identify error-prone parts of the design, as well as coverage holes.
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| 39. |
- Borg, Sixten, et al.
(author)
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Cost effectiveness of pomalidomide in patients with relapsed and refractory multiple myeloma in Sweden
- 2016
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In: Acta Oncologica. - 0284-186X. ; 55:5, s. 554-560
-
Journal article (peer-reviewed)abstract
- Background: Multiple myeloma (MM) patients who have progressed following treatment with both bortezomib and lenalidomide have a poor prognosis. In this late stage, other effective alternatives are limited, and patients in Sweden are often left with best supportive care. Pomalidomide is a new anti-angiogenic and immunomodulatory drug for the treatment of MM. Our objective was to evaluate the cost effectiveness of pomalidomide as an add-on to best supportive care in patients with relapsed and refractory MM in Sweden. Material and methods: We developed a health-economic discrete event simulation model of a patient’s course through stable disease and progressive disease, until death. It estimates life expectancy, quality-adjusted life years (QALYs) and costs from a societal perspective. Effectiveness data and utilities were taken from the MM-003 trial comparing pomalidomide plus low-dose dexamethasone with high-dose dexamethasone (HIDEX). Cost data were taken from official Swedish price lists, government sources and literature. Results: The model estimates that, if a patient is treated with HIDEX, life expectancy is 1.12 years and the total cost is SEK 179 976 (€19 100), mainly indirect costs. With pomalidomide plus low-dose dexamethasone, life expectancy is 2.33 years, with a total cost of SEK 767 064 (€81 500), mainly in drug and indirect costs. Compared to HIDEX, pomalidomide treatment gives a QALY gain of 0.7351 and an incremental cost of SEK 587 088 (€62 400) consisting of increased drug costs (59%), incremental indirect costs (33%) and other healthcare costs (8%). The incremental cost-effectiveness ratio is SEK 798 613 (€84 900) per QALY gained. Conclusion: In a model of late-stage MM patients with a poor prognosis in the Swedish setting, pomalidomide is associated with a relatively high incremental cost per QALY gained. This model was accepted by the national Swedish reimbursement authority TLV, and pomalidomide was granted reimbursement in Sweden.
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| 40. |
- Boscolo Bibi, Sara, 1993-, et al.
(author)
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Multi-spectroscopic study of electrochemically-formed oxide-derived gold electrodes
- 2024
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In: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry. - 1463-9076 .- 1463-9084. ; 26:3, s. 2332-2340
-
Journal article (peer-reviewed)abstract
- Oxide-derived metals are produced by reducing an oxide precursor. These materials, including gold, have shown improved catalytic performance over many native metals. The origin of this improvement for gold is not yet understood. In this study, operando non-resonant sum frequency generation (SFG) and ex situ high-pressure X-ray photoelectron spectroscopy (HP-XPS) have been employed to investigate electrochemically-formed oxide-derived gold (OD-Au) from polycrystalline gold surfaces. A range of different oxidizing conditions were used to form OD-Au in acidic aqueous medium (H3PO4, pH = 1). Our electrochemical data after OD-Au is generated suggest that the surface is metallic gold, however SFG signal variations indicate the presence of subsurface gold oxide remnants between the metallic gold surface layer and bulk gold. The HP-XPS results suggest that this subsurface gold oxide could be in the form of Au2O3 or Au(OH)3. Furthermore, the SFG measurements show that with reducing electrochemical treatments the original gold metallic state can be restored, meaning the subsurface gold oxide is released. This work demonstrates that remnants of gold oxide persist beneath the topmost gold layer when the OD-Au is created, potentially facilitating the understanding of the improved catalytic properties of OD-Au.
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| 41. |
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| 42. |
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| 43. |
- Bridel, Claire, et al.
(author)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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In: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
-
Research review (peer-reviewed)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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| 44. |
- Båth, Magnus, 1974, et al.
(author)
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A conceptual optimisation strategy for radiography in a digital environment.
- 2005
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In: Radiation protection dosimetry. - : Oxford University Press (OUP). - 0144-8420 .- 1742-3406. ; 114:1-3, s. 230-5
-
Journal article (peer-reviewed)abstract
- Using a completely digital environment for the entire imaging process leads to new possibilities for optimisation of radiography since many restrictions of screen/film systems, such as the small dynamic range and the lack of possibilities for image processing, do not apply any longer. However, at the same time these new possibilities lead to a more complicated optimisation process, since more freedom is given to alter parameters. This paper focuses on describing an optimisation strategy that concentrates on taking advantage of the conceptual differences between digital systems and screen/film systems. The strategy can be summarised as: (a) always include the anatomical background during the optimisation, (b) perform all comparisons at a constant effective dose and (c) separate the image display stage from the image collection stage. A three-step process is proposed where the optimal setting of the technique parameters is determined at first, followed by an optimisation of the image processing. In the final step the optimal dose level-given the optimal settings of the image collection and image display stages-is determined.
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| 45. |
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| 46. |
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| 47. |
- Carlsson, Peter, et al.
(author)
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Success factors in the process of establishing a TechCenter
- 2011
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Book (other academic/artistic)abstract
- What is the success factors when establishing a TechCenter? This thesis describes the possible success factors when establishing a TechCenter within a IT-University in Göteborg, Sweden. This thesis also describes a possible definition of what a TechCenter is, its purpose as a department in an organization and introduces the term TechCenter as a neologism. The success factors are established through analysis of a number of interviews and also through the use of questionnaires. The empirical data are gathered from people important to the TechCenter project at the IT-University in Göteborg, including the faculty, academic initiatives from private corporations and staff from organizations similar to the TechCenter project. This thesis can also be used as inspiration to other universities planning to create a TechCenter.
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| 48. |
- Chuan Chen, Max, et al.
(author)
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Low temperature activation of B implantation of Si subcell fabrication in III-V/Si tandem solar cells
- 2019
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In: Proceedings of the 36<sup>th</sup> EU PVSEC 2019. - : WIP. - 3936338604 ; , s. 764-768
-
Conference paper (other academic/artistic)abstract
- In this work, we investigated the Si pre-amorphization implantation (PAI) assisted low temperatureannealing process to activate boron implantation in n-Si in a hydride vapor phase epitaxy (HVPE) reactor, which canbe used for the Si subcell fabrication in the III-V/Si tandem solar cells enabled by the corrugated epitaxial lateralovergrowth (CELOG). A uniform boron activation in Si and a low emitter sheet resistance of 77 /sq was obtained atannealing temperatures of 600-700°C. High-resolution x-ray diffraction was used to study the recrystallization ofamorphous silicon and the incorporation of boron dopants in Si. Hall measurements revealed p-type carrierconcentrations in the order of 1020 cm-3. The n-Si wafers with B implantation activated at 700°C by HVPE wereprocessed to solar cells and characterized by the standard light-current-voltage measurement under AM1.5 spectrumand external quantum efficiency measurements. The developed B implantation and low temperature activationprocesses are applied to the InP/Si seed template preparation for CELOG, on which CELOG GaInP over a Si subcellwith a direct heterojunction was demonstrated.
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| 49. |
- Cippitelli, Andrea, et al.
(author)
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Neuropeptide Y (NPY) suppresses yohimbine-induced reinstatement of alcohol seeking
- 2010
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In: Psychopharmacology. - : Springer. - 0033-3158 .- 1432-2072. ; 208:3, s. 417-426
-
Journal article (peer-reviewed)abstract
- INTRODUCTION: Reinstatement of responding to a previously alcohol-associated lever following extinction is an established model of relapse-like behavior and can be triggered by stress exposure. Here, we examined whether neuropeptide Y (NPY), an endogenous anti-stress mediator, blocks reinstatement of alcohol-seeking induced by the pharmacological stressor yohimbine.MATERIALS AND METHODS: NPY [5.0 or 10.0 mug/rat, intracerebroventricularly (ICV)] dose-dependently blocked the reinstatement of alcohol seeking induced by yohimbine (1.25 mg/kg, i.p.) but failed to significantly suppress the maintenance of alcohol self-administration. We then used c-fos expression mapping to examine neuronal activation following treatment with yohimbine or NPY alone or yohimbine following NPY pre-treatment.RESULTS AND DISCUSSION: The analysis was focused on a network of structures previously implicated in yohimbine-induced reinstatement, comprised of central (CeA) and basolateral (BLA) amygdala and the shell of the nucleus accumbens (Nc AccS). Within this network, both yohimbine and NPY potently induced neuronal activation, and their effects were additive, presumably indicating activation of excitatory and inhibitory neuronal populations, respectively.CONCLUSION: These results suggest that NPY selectively suppresses relapse to alcohol seeking induced by stressful events and support the NPY system as an attractive target for the treatment of alcohol addiction.
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| 50. |
- Colombo, Simone, et al.
(author)
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Mining players’ experience in computer games: Immersion affects flow but not presence
- 2023
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In: Computers in Human Behavior Reports. - : Elsevier. - 2451-9588. ; 12
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Journal article (peer-reviewed)abstract
- Understanding how different levels of immersion influence the experiences of flow and presence can shed light on the intricate interplay between these constructs and provide valuable insights into the factors that contribute to engaging and immersive gameplay. The independent variable, immersion, was manipulated in three conditions (high, moderate, and low) in a between-subject design within the video game Minecraft. Participants were asked to complete 15 min of gameplay and then fill out the questionnaires concerning flow and presence. The experiment was conducted remotely on a video-sharing platform. Bayesian analysis revealed an effect of immersion level on flow, while no evidence of an effect was found for the experience of presence. This study provides evidence in favor of a relation between flow and immersion while supporting a presumed double dissociation of immersion from presence. Future research using a Bayesian approach is encouraged to build further knowledge on this research topic.
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