| 1. |
- McCreary, D., et al.
(författare)
-
Development and Validation of a Targeted Next-Generation Sequencing Gene Panel for Children With Neuroinflammation
- 2019
-
Ingår i: Jama Network Open. - : American Medical Association (AMA). - 2574-3805. ; 2:10
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Neuroinflammatory disorders are a range of severe neurological disorders causing brain and spinal inflammation and are now increasingly recognized in the pediatric population. They are often characterized by marked genotypic and phenotypic heterogeneity, complicating diagnostic work in clinical practice and molecular diagnosis. OBJECTIVE To develop and evaluate a next-generation sequencing panel targeting genes causing neuroinflammation or mimicking neuroinflammation. DESIGN, SETTING, AND PARTICIPANTS Cohort study in which a total of 257 genes associated with monogenic neuroinflammation and/or cerebral vasculopathy, including monogenic noninflammatory diseases mimicking these entities, were selected. A customized enrichment capture array, the neuroinflammation gene panel (NIP), was created. Targeted high-coverage sequencing was applied to DNA samples taken from eligible patients referred to Great Ormond Street Hospital in London, United Kingdom, between January 1, 2017, and January 30, 2019, because of onset of disease early in life, family history, and/or complex neuroinflammatory phenotypes. MAIN OUTCOMES AND MEASURES The main outcome was the percentage of individuals with definitive molecular diagnoses, variant classification, and clinical phenotyping of patients with pathogenic variants identified using the NIP panel. The NIP panel was initially validated in 16 patients with known genetic diagnoses. RESULTS The NIP was both sensitive (95%) and specific (100%) for detection of known mutations, including gene deletions, copy number variants, small insertions and deletions, and somatic mosaicism with allele fraction as low as 3%. Prospective testing of 60 patients (30 [50%] male; median [range] age, 9.8 [0.8-20] years) presenting with heterogeneous neuroinflammatory phenotypes revealed at least 1 class 5 (clearly pathogenic) variant in 9 of 60 patients (15%); 18 of 60 patients (30%) had at least 1 class 4 (likely pathogenic) variant. Overall, a definitive molecular diagnosis was established in 12 of 60 patients (20%). CONCLUSIONS AND RELEVANCE The NIP was associated with molecular diagnosis in this cohort and complemented routine laboratory and radiological workup of patients with neuroinflammation. Unexpected genotype-phenotype associations in patients with pathogenic variants deviating from the classic phenotype were identified. Obtaining an accurate molecular diagnosis in a timely fashion informed patient management, including successful targeted treatment in some instances and early institution of hematopoietic stem cell transplantation in others.
|
|
| 2. |
- Meeren, H. K. M., et al.
(författare)
-
Early Preferential Responses to Fear Stimuli in Human Right Dorsal Visual Stream - A Meg Study
- 2016
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Emotional expressions of others are salient biological stimuli that automatically capture attention and prepare us for action. We investigated the early cortical dynamics of automatic visual discrimination of fearful body expressions by monitoring cortical activity using magnetoencephalography. We show that right parietal cortex distinguishes between fearful and neutral bodies as early as 80-ms after stimulus onset, providing the first evidence for a fast emotion-attention-action link through human dorsal visual stream.
|
|
| 3. |
- Strondl, Annika, et al.
(författare)
-
Innovative powder based manufacturing of high performance gears
- 2016
-
Ingår i: World PM 2016 Congress and Exhibition. - : European Powder Metallurgy Association (EPMA). - 9781899072484
-
Konferensbidrag (refereegranskat)abstract
- There are strong driving forces towards high-performance gear wheels which can handle higher engine outputs, or allow more compact designs of transmissions. Today the performance and life of conventionally manufactured gear wheels are limited by factors such as inhomogeneous microstructure and distribution of inclusions. Powder metallurgy (PM) can solve some of these problems but has so far had limitations caused by porosity. In this paper a cost effective way to eliminate porosity by HIP-ing without canister has been evaluated with encouraging results. Parameters such as powder particle size, lubricant and double pressing have been evaluated in the PM route in order to get a gas tight surface enabling effective post HIP-ing. So far double pressing has given promising results. Challenges such as open porosity, surface porosity and inclusions are addressed in the paper.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Frisk, Karin, et al.
(författare)
-
Characterisation of EBM-built shelled samples of Ti6Al4V compacted by HIP
- 2016
-
Ingår i: World PM 2016 Congress and Exhibition. - : European Powder Metallurgy Association (EPMA). - 9781899072484
-
Konferensbidrag (refereegranskat)abstract
- Compaction of additively manufactured Ti6Al4V components by Hot Isostatic Pressing (HIP) is often applied to eliminate porosity, producing fully dense material. In the present work shelled samples produced by Electron Beam Melting with the Arcam process (EBM) were compacted by HIP to produce fully dense samples. Cylindrical samples were studied. The walls of the cylinders were built with EBM, and the powder from the process was left uncompacted inside the cylinders. Samples with different wall thicknesses were produced. The samples were thereafter subjected to a HIP compaction. The critical wall thicknesses needed for compaction were evaluated, and the microstructures characterized. The results show that fully dense samples, with very fine microstructures, are possible.
|
|
| 7. |
- Hamalainen, Sanna, et al.
(författare)
-
Coxsackievirus B1 Reveals Strain Specific Differences in Plasmacytoid Dendritic Cell Mediated Immunogenicity
- 2014
-
Ingår i: Journal of Medical Virology. - : Wiley. - 0146-6615 .- 1096-9071. ; 86:8, s. 1412-1420
-
Tidskriftsartikel (refereegranskat)abstract
- Enterovirus infections are usually mild but can also cause severe illnesses and play a role in chronic diseases, such as cardiomyopathies and type 1 diabetes. Host response to the invading virus can markedly modulate the course of the infection, and this response varies between individuals due to the polymorphism of immune response genes. However, it is currently not known if virus strains also differ in their ability to stimulate the host immune system. Coxsackievirus B1 (CBV1) causes severe epidemics in young infants and it has recently been connected with type 1 diabetes in seroepidemiological studies. This study evaluated the ability of different field isolates of CBV1 to induce innate immune responses in PBMCs. CBV1 strains differed markedly in their capacity to induce innate immune responses. Out of the 18 tested CBV1 strains two induced exceptionally strong alpha interferon (IFN-alpha) response in PBMC cultures. The responding cell type was found to be the plasmacytoid dendritic cell. Such a strong innate immune response was accompanied by an up-regulation of several other immune response genes and secretion of cytokines, which modulate inflammation, and adaptive immune responses. These results suggest that enterovirus-induced immune activation depends on the virus strain. It is possible that the immunotype of the virus modulates the course of the infection and plays a role in the pathogenesis of chronic immune-mediated enterovirus diseases.
|
|
| 8. |
- Leicht, Alexander, 1987, et al.
(författare)
-
As-HIP microstructure of EBM fabricated shell components
- 2016
-
Ingår i: World PM 2016 Congress and Exhibition. - : European Powder Metallurgy Association (EPMA). - 9781899072484
-
Konferensbidrag (refereegranskat)abstract
- Electron Beam Melting (EBM) was used to build Ti-6Al-4V cylindrical shell samples with different wall thickness filled with powder. Built shell samples were HIPed and the difference in microstructure between the EBM-built walls and densified powder inside the shell components was studied as well as the cohesion between these two regions. Components characterization utilizing LOM and SEM+EBSD indicates that columnar grain growth was consistent before and after HIP in the EBM-built part of the components (walls), whereas the densified material in the center of the component had a fine isotropic microstructure, characteristic for HIPed material. The combination of EBM and HIP is shown to be an attractive way of manufacturing complex-shape full density components for high performance applications, involving shortening of built time in the EBM-processing and lead time in capsule fabrication for HIP.
|
|
| 9. |
|
|
| 10. |
- Lindberg, B., et al.
(författare)
-
Previous exposure to measles, mumps, and rubella--but not vaccination during adolescence--correlates to the prevalence of pancreatic and thyroid autoantibodies.
- 1999
-
Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 104:1, s. 1-5
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: This study was designed to determine whether a relationship exists between previous exposure to measles, mumps, and rubella (MMR) by natural infection or vaccination or by new immunization with MMR vaccine, and either the presence or levels of autoantibodies against thyroid cell and pancreatic beta-cell antigens. METHODS: Antibodies against MMR and autoantibodies against thyroglobulin, thyroid peroxidase, pancreas islet cells (ICA), islet cell surface, glutamic acid decarboxylase 65k autoantibodies, and insulin were studied before, and 3 months after, vaccination with combined MMR vaccine in 386 school children between 11 and 13 years of age. RESULTS: The vaccination changed neither the prevalence nor the level of autoantibodies. Children with rubella antibodies before vaccination had higher levels of ICA than did the rubella seronegative children. In contrast, thyroid autoantibody levels and prevalence were lower in children with antibodies against measles, mumps, or both before vaccination than in children without those antibodies. CONCLUSIONS: Previous natural infection or vaccination against measles, mumps, or both seemed to have an inhibitory effect on the development of thyroid autoantibodies. In contrast, children with previous exposure to rubella had higher levels of ICA. No evidence was found that MMR vaccination during adolescence may trigger autoimmunity.
|
|
