| 1. |
- Stray-Pedersen, Asbjorg, et al.
(författare)
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Primary immunodeficiency diseases : Genomic approaches delineate heterogeneous Mendelian disorders
- 2017
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Ingår i: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 139:1, s. 232-245
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Tidskriftsartikel (refereegranskat)abstract
- Background: Primary immunodeficiency diseases (PIDDs) are clinically and genetically heterogeneous disorders thus far associated with mutations in more than 300 genes. The clinical phenotypes derived from distinct genotypes can overlap. Genetic etiology can be a prognostic indicator of disease severity and can influence treatment decisions. Objective: We sought to investigate the ability of whole-exome screening methods to detect disease-causing variants in patients with PIDDs. Methods: Patients with PIDDs from 278 families from 22 countries were investigated by using whole-exome sequencing. Computational copy number variant (CNV) prediction pipelines and an exome-tiling chromosomal microarray were also applied to identify intragenic CNVs. Analytic approaches initially focused on 475 known or candidate PIDD genes but were nonexclusive and further tailored based on clinical data, family history, and immunophenotyping. Results: A likely molecular diagnosis was achieved in 110 (40%) unrelated probands. Clinical diagnosis was revised in about half (60/ 110) and management was directly altered in nearly a quarter (26/ 110) of families based on molecular findings. Twelve PIDD-causing CNVs were detected, including 7 smaller than 30 Kb that would not have been detected with conventional diagnostic CNV arrays. Conclusion: This high-throughput genomic approach enabled detection of disease-related variants in unexpected genes; permitted detection of low-grade constitutional, somatic, and revertant mosaicism; and provided evidence of a mutational burden in mixed PIDD immunophenotypes.
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| 2. |
- Andersson, Bodil, et al.
(författare)
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Combining Keystroke Logging with Eye Tracking
- 2006
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Ingår i: Writing and Digital Media. - 1572-6304. - 0080448631 ; 17, s. 166-172
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Bokkapitel (refereegranskat)abstract
- This chapter describes the successful development of a new methodology for studying on-line writing. The text-logging tool ScriptLog has been combined with the eyetracking technology iView X HED HT, in order to enhance the study of the interplay between writing, monitoring and revision. Data on the distribution of visual attention during writing help determining to what extent pauses are used for monitoring. The complexity of the experimental settings, and the expertise needed for interpreting the eye-tracking data make this a method suitable mainly for laboratory settings. The chapter also introduces an analysis tool that merges data from ScriptLog and iView and thus helps the researcher to organise and analyse the vast amount of data produced.
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| 3. |
- Bergemalm, Daniel, 1977-, et al.
(författare)
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Systemic Inflammation in Preclinical Ulcerative Colitis
- 2021
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Ingår i: Gastroenterology. - : AGA Institute. - 0016-5085 .- 1528-0012. ; 161:5, s. 1526-1539.e9
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Preclinical ulcerative colitis is poorly defined. We aimed to characterize the preclinical systemic inflammation in ulcerative colitis, using a comprehensive set of proteins.Methods: We obtained plasma samples biobanked from individuals who developed ulcerative colitis later in life (n = 72) and matched healthy controls (n = 140) within a population-based screening cohort. We measured 92 proteins related to inflammation using a proximity extension assay. The biologic relevance of these findings was validated in an inception cohort of patients with ulcerative colitis (n = 101) and healthy controls (n = 50). To examine the influence of genetic and environmental factors on these markers, a cohort of healthy twin siblings of patients with ulcerative colitis (n = 41) and matched healthy controls (n = 37) were explored.Results: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP-1) were up-regulated (P < .05) in preclinical ulcerative colitis compared with controls based on both univariate and multivariable models. Ingenuity Pathway Analyses identified several potential key regulators, including interleukin-1β, tumor necrosis factor, interferon-gamma, oncostatin M, nuclear factor-κB, interleukin-6, and interleukin-4. For validation, we built a multivariable model to predict disease in the inception cohort. The model discriminated treatment-naïve patients with ulcerative colitis from controls with leave-one-out cross-validation (area under the curve = 0.92). Consistently, MMP10, CXCL9, CXCL11, and MCP-1, but not CCL11 and SLAMF1, were significantly up-regulated among the healthy twin siblings, even though their relative abundances seemed higher in incident ulcerative colitis.Conclusions: A set of inflammatory proteins are up-regulated several years before a diagnosis of ulcerative colitis. These proteins were highly predictive of an ulcerative colitis diagnosis, and some seemed to be up-regulated already at exposure to genetic and environmental risk factors.
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| 4. |
- Collan, Camilla, et al.
(författare)
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To capture the child's interest - nurses experiences of 'Saga stories in health talks'.
- 2024
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Ingår i: BMC Nursing. - : BioMed Central (BMC). - 1472-6955. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: As unhealthy lifestyle habits have been found to be established early in life and often track into adulthood, early preventive initiatives are important. 'Saga Stories in health talks' is a newly developed material that is intended to be used as a support for nurses at child health care (CHC) centers in their health talks with children and parents in Sweden. The aim of this study is to explore how CHC nurses experience the usability of the 'Saga Stories in health talks' material.METHODS: This study used a qualitative design. The material 'Saga Stories in health talks' was tested by 33 CHC nurses working in 11 CHC centers in three regions in Sweden. All CHC nurses were invited to participate in the interviews and 17 agreed. The interviews were transcribed and analysed using content analysis.RESULTS: Three categories and eight sub-categories emerged. The categories were: (1) An appreciated tool suitable for health talks, (2) Illustrations to capture children's interest in the conversation with families, and (3) Barriers and facilitators. Saga Stories in health talks' was experienced by the CHC nurses as an appreciated tool with content highly relevant to what should be discussed during the health talks. The CHC nurses described the material as well-designed with illustrations that helped them capture the child's interest and increase their participation, while still involving the parents. Support from colleagues, the researchers, and managers were seen as important facilitators. Challenges included structural factors such as how and when to best use the material, especially concerning that the 4-year visit contained many other mandatory parts.CONCLUSIONS: This pilot study show that the material 'Saga Stories in health talks' was highly appreciated by CHC nurses and facilitated their health talks with families in CHC. Important aspects with the material were the relevant content and the focus on healthy living habits, as well as the child friendly illustrations. These findings can be used when similar material is developed to facilitate health talks with families in other contexts. Our results also highlight the importance to adjust the implementation of a new material with already established practice and routines.
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| 7. |
- Delvallée, Clarisse, et al.
(författare)
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A BBS1 SVA F retrotransposon insertion is a frequent cause of Bardet-Biedl syndrome
- 2021
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Ingår i: Clinical Genetics. - : John Wiley & Sons. - 0009-9163 .- 1399-0004. ; 99:2, s. 318-324
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Tidskriftsartikel (refereegranskat)abstract
- Bardet-Biedl syndrome (BBS) is a ciliopathy characterized by retinitis pigmentosa, obesity, polydactyly, cognitive impairment and renal failure. Pathogenic variants in 24 genes account for the molecular basis of >80% of cases. Toward saturated discovery of the mutational basis of the disorder, we carefully explored our cohorts and identified a hominid-specific SINE-R/VNTR/Alu type F (SVA-F) insertion in exon 13 of BBS1 in eight families. In six families, the repeat insertion was found in trans with c.1169 T > G, p.Met390Arg and in two families the insertion was found in addition to other recessive BBS loci. Whole genome sequencing, de novo assembly and SNP array analysis were performed to characterize the genomic event. This insertion is extremely rare in the general population (found in 8 alleles of 8 BBS cases but not in >10 800 control individuals from gnomAD-SV) and due to a founder effect. Its 2435 bp sequence contains hallmarks of LINE1 mediated retrotransposition. Functional studies with patient-derived cell lines confirmed that the BBS1 SVA-F is deleterious as evidenced by a significant depletion of both mRNA and protein levels. Such findings highlight the importance of dedicated bioinformatics pipelines to identify all types of variation.
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| 8. |
- Frid, Johan, et al.
(författare)
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r-ljuden i svenskan
- 2010
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Ingår i: Språken i Sverige. - Stockholm : Norstedts kartor. - 9187760576 ; , s. 66-67, s. 66-67
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 9. |
- Halim, Danny, et al.
(författare)
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ACTG2 variants impair actin polymerization in sporadic Megacystis Microcolon Intestinal Hypoperistalsis Syndrome
- 2016
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 25:3, s. 571-583
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Tidskriftsartikel (refereegranskat)abstract
- Megacystis Microcolon Intestinal Hypoperistalsis Syndrome (MMIHS) is a rare congenital disorder, in which heterozygous missense variants in the Enteric Smooth Muscle actin gamma-2 (ACTG2) gene have been recently identified. To investigate the mechanism by which ACTG2 variants lead to MMIHS, we screened a cohort of eleven MMIHS patients, eight sporadic and three familial cases, and performed immunohistochemistry, molecular modeling and molecular dynamics (MD) simulations, and in vitro assays. In all sporadic cases, a heterozygous missense variant in ACTG2 was identified. ACTG2 expression was detected in all intestinal layers where smooth muscle cells are present in different stages of human development. No histopathological abnormalities were found in the patients. Using molecular modeling and MD simulations, we predicted that ACTG2 variants lead to significant changes to the protein function. This was confirmed by in vitro studies, which showed that the identified variants not only impair ACTG2 polymerization, but also contribute to reduced cell contractility. Taken together, our results confirm the involvement of ACTG2 in sporadic MMIHS, and bring new insights to MMIHS pathogenesis.
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