| 1. |
- Marenholz, I, et al.
(författare)
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Meta-analysis identifies seven susceptibility loci involved in the atopic march
- 2015
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6, s. 8804-
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Tidskriftsartikel (refereegranskat)abstract
- Eczema often precedes the development of asthma in a disease course called the ‘atopic march’. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P=2.1 × 10−8) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P=5.3 × 10−9). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.
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| 2. |
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| 3. |
- Camuffo, I, et al.
(författare)
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State of the art and eVALUE scope
- 2008
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- eVALUE will address the real function of ICT-based safety systems and their capability to perform the function through two courses of action: defining and quantifying the function output to be achieved by the safety system and developing the testing and evaluation methods for the ICT-based safety systems. The safety systems within the eVALUE scope are classified into four clusters: longitudinal, lateral and yaw/stability. The fourth cluster remains open for upcoming systems. Based on market availability and penetration rate, the consortium decided to focus on eight preventive or mitigating safety systems: ACC, FCW and CM by braking, in the longitudinal assistance domain; BSD, LDW and LKA, in the lateral assistance domain; and finally, ABS and ESC, in the yaw/stability assistance domain. Following the description of current test and evaluation methods, sensor technologies, system function output and ECUs globally applicable to ICT based safety systems, the report covers these technologies and components for the eight selected systems in detail. As a next step to this deliverable and according to the work plan, concepts for design reviews, physical vehicle testing as well as laboratory testing will be analysed. The result will be an in-depth understanding of the possibilities to investigate and evaluate the eight active safety systems within the first phase of the project. The different concepts will then support the decision about the development of the testing and evaluation methods that are able to point out the safety benefit of those systems in the most representative way.
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| 4. |
- Hilbert, Kevin, et al.
(författare)
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Cortical and Subcortical Brain Alterations in Specific Phobia and Its Animal and Blood-Injection-Injury Subtypes: A Mega-Analysis From the ENIGMA Anxiety Working Group.
- 2024
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Ingår i: The American Journal of Psychiatry. - 1535-7228. ; 181:8, s. 728-740
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Tidskriftsartikel (refereegranskat)abstract
- Specific phobia is a common anxiety disorder, but the literature on associated brain structure alterations exhibits substantial gaps. The ENIGMA Anxiety Working Group examined brain structure differences between individuals with specific phobias and healthy control subjects as well as between the animal and blood-injection-injury (BII) subtypes of specific phobia. Additionally, the authors investigated associations of brain structure with symptom severity and age (youths vs. adults).Data sets from 31 original studies were combined to create a final sample with 1,452 participants with phobia and 2,991 healthy participants (62.7% female; ages 5-90). Imaging processing and quality control were performed using established ENIGMA protocols. Subcortical volumes as well as cortical surface area and thickness were examined in a preregistered analysis.Compared with the healthy control group, the phobia group showed mostly smaller subcortical volumes, mixed surface differences, and larger cortical thickness across a substantial number of regions. The phobia subgroups also showed differences, including, as hypothesized, larger medial orbitofrontal cortex thickness in BII phobia (N=182) compared with animal phobia (N=739). All findings were driven by adult participants; no significant results were observed in children and adolescents.Brain alterations associated with specific phobia exceeded those of other anxiety disorders in comparable analyses in extent and effect size and were not limited to reductions in brain structure. Moreover, phenomenological differences between phobia subgroups were reflected in diverging neural underpinnings, including brain areas related to fear processing and higher cognitive processes. The findings implicate brain structure alterations in specific phobia, although subcortical alterations in particular may also relate to broader internalizing psychopathology.
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| 5. |
- Camuffo, I, et al.
(författare)
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Concepts definition
- 2009
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Rapport (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Lindblom, Rickard P. F., et al.
(författare)
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Complement receptor 2 is up regulated in the spinal cord following nerve root injury and modulates the spinal cord response
- 2015
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Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Activation of the complement system has been implicated in both acute and chronic states of neurodegeneration. However, a detailed understanding of this complex network of interacting components is still lacking. Methods: Large-scale global expression profiling in a rat F2(DAxPVG) intercross identified a strong cis-regulatory influence on the local expression of complement receptor 2 (Cr2) in the spinal cord after ventral root avulsion (VRA). Expression of Cr2 in the spinal cord was studied in a separate cohort of DA and PVG rats at different time-points after VRA, and also following sciatic nerve transection (SNT) in the same strains. Consequently, Cr2(-/-) mice and Wt controls were used to further explore the role of Cr2 in the spinal cord following SNT. The in vivo experiments were complemented by astrocyte and microglia cell cultures. Results: Expression of Cr2 in naive spinal cord was low but strongly up regulated at 5-7 days after both VRA and SNT. Levels of Cr2 expression, as well as astrocyte activation, was higher in PVG rats than DA rats following both VRA and SNT. Subsequent in vitro studies proposed astrocytes as the main source of Cr2 expression. A functional role for Cr2 is suggested by the finding that transgenic mice lacking Cr2 displayed increased loss of synaptic nerve terminals following nerve injury. We also detected increased levels of soluble CR2 (sCR2) in the cerebrospinal fluid of rats following VRA. Conclusions: These results demonstrate that local expression of Cr2 in the central nervous system is part of the axotomy reaction and is suggested to modulate subsequent complement mediated effects.
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| 7. |
- Lindblom, Rickard P. F., et al.
(författare)
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Unbiased expression mapping identifies a link between the complement and cholinergic systems in the rat central nervous system
- 2014
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 192:3, s. 1138-1153
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Tidskriftsartikel (refereegranskat)abstract
- The complement system is activated in a wide spectrum of CNS diseases and is suggested to play a role in degenerative phenomena such as elimination of synaptic terminals. Still, little is known of mechanisms regulating complement activation in the CNS. Loss of synaptic terminals in the spinal cord after an experimental nerve injury is increased in the inbred DA strain compared with the PVG strain and is associated with expression of the upstream complement components C1q and C3, in the absence of membrane attack complex activation and neutrophil infiltration. To further dissect pathways regulating complement expression, we performed genome-wide expression profiling and linkage analysis in a large F2(DA × PVG) intercross, which identified quantitative trait loci regulating expression of C1qa, C1qb, C3, and C9. Unlike C1qa, C1qb, and C9, which all displayed distinct coregulation with different cis-regulated C-type lectins, C3 was regulated in a coexpression network immediately downstream of butyrylcholinesterase. Butyrylcholinesterase hydrolyses acetylcholine, which exerts immunoregulatory effects partly through TNF-α pathways. Accordingly, increased C3, but not C1q, expression was demonstrated in rat and mouse glia following TNF-α stimulation, which was abrogated in a dose-dependent manner by acetylcholine. These findings demonstrate new pathways regulating CNS complement expression using unbiased mapping in an experimental in vivo system. A direct link between cholinergic activity and complement activation is supported by in vitro experiments. The identification of distinct pathways subjected to regulation by naturally occurring genetic variability is of relevance for the understanding of disease mechanisms in neurologic conditions characterized by neuronal injury and complement activation.
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| 8. |
- Perlet, C, et al.
(författare)
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Magnetic resonance-guided, vacuum-assisted breast biopsy - Results from a European Multicenter Study of 538 lesions
- 2006
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Ingår i: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 106:5, s. 982-990
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. The objective of this study was to determine the accuracy, reproducibility, and clinical value of magnetic resonance (MR)-guided, vacuum-assisted breast biopsy (MR-VAB) in a prospective, multicenter study. METHODS. in 5 European centers, MR-VAB was performed or attempted on 538 suspicious lesions that were visible or could targeted only by MR imaging (MRI). Verification of malignant or borderline lesions included reexcision of the biopsy cavity. Benign biopsy results were verified by retrospective correlation of histology with preinterventional and postinterventional MRI studies. Follow-up of 24-48 months (median, 32 months) was available for 491 of 538 patients. RESULTS. MR-VAB was unsuccessful or was not completed in 21 of 538 patients, for which an immediate repeat biopsy was recommended. Five hundred seventeen of 538 performed VAB procedures (96%) were successful. Histology yielded 138 (27%) malignancies, 17 (3%) atypical ductal hyperplasias, and 362 (70%) benign entities. No false-negative diagnoses occurred among the 517 successful MR-VAB procedures. The positive predictive value of VAB depended on patient preselection, which differed according to the indication for the initial MRI study. CONCLUSIONS. The results of this study indicated that MR-VAB offers excellent accuracy. Small lesion size did not prove to be a limitation.
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| 9. |
- Perlet, C, et al.
(författare)
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Multicenter study for the evaluation of a dedicated biopsy device for MR-guided vacuum biopsy of the breast
- 2002
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Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 12:6, s. 1463-1470
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this multicenter study was to determine the accuracy and clinical value of a dedicated breast biopsy system which allows for MR-guided vacuum biopsy (VB) of contrast-enhancing lesions. In five European centers, MR-guided 11-gauge VB was performed on 341 lesions. In 7 cases VB was unsuccessful. This was immediately realized on postinterventional images or direct follow-up combined with histopathology-imaging correlation; thus, a false-negative diagnosis was avoided. Histology of 334 successful biopsies yielded 84 (25%) malignancies, 17 (5%) atypical ductal hyperplasias, and 233 (70%) benign entities. Verification of malignant or borderline lesions included re-excision of the biopsy cavity. Benign histologic biopsy results were verified by retrospective correlation with the pre- and postinterventional MRI and by subsequent follow-up. Our results indicate that MR-guided VB, in combination with the dedicated biopsy coil, offers the possibility to accurately diagnose even very small lesions that can only be visualized or localized by MRI.
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