| 1. |
- Björklund, Camilla, et al.
(författare)
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Matematikkundervisning
- 2013
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Denna boken är skriven av en grupp erfarna norska och svenska lärarutbildare i matematik. Boken bygger på utprövad erfarenhet - såväl egen som andras - och på aktuell, relevant forskning i matematikdidaktik. Texten väver samman matematik och matematikdidaktik, det vill säga ämnet som det undervisas i och frågor om hur ämnet kan läras och undervisas. Boken innehåller det som är absolut viktigast att få med sig i den grundläggande lärarutbildningen i matmatik.
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| 2. |
- Clausen, Henning, et al.
(författare)
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Evaluation of Circulating Cardiovascular Biomarker Levels for Early Detection of Congenital Heart Disease in Newborns in Sweden
- 2020
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Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 3:12
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Congenital heart disease (CHD) is the most common congenital malformation in humans worldwide. Circulating cardiovascular biomarkers could potentially improve the early detection of CHD, even in asymptomatic newborns. Objectives: To assess the performance of a dried blood spot (DBS) test to measure the cardiovascular biomarker amino terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP) levels in newborns and to compare DBS with standard EDTA analysis in control newborns during the first week of life. Design, Setting, and Participants: This diagnostic study was conducted in a single regional pediatric service in southern Sweden. Healthy, term neonates born between July 1, 2018, and May 31, 2019, were prospectively enrolled and compared against retrospectively identified newborns with CHD born between September 1, 2003, and September 30, 2019. Neonates who required inpatient treatment beyond the standard postnatal care were excluded. Exposure: New DBS test for NT-proBNP quantification in newborns that used 3 μL of blood vs the current screening standard. Main Outcomes and Measures: Performance of the new test and when combined with pulse oximetry screening was measured by receiver operating characteristic curve analysis. Performance of the new test and EDTA screening was compared using Pearson linear correlation analysis. Results: The DBS samples of 115 neonates (81 control newborns and 34 newborns with CHD, of whom 63 were boys [55%] and the mean [SD] gestational age was 39.6 [1.4] weeks) were analyzed. The new NT-proBNP test alone identified 71% (n = 24 of 34) of all CHD cases and 68% (n = 13 of 19) of critical CHD cases as soon as 2 days after birth. Detection of any CHD type improved to 82% (n = 28 of 34 newborns) and detection of critical CHD improved to 89% (n = 17 of 19 newborns) when combined pulse oximetry screening and NT-proBNP test results were used. Performance of the NT-proBNP test was excellent when control newborns were matched to newborns with CHD born between July 1, 2018, and May 31, 2019 (area under the curve, 0.96; SE, 0.027; 95% CI, 0.908-1.0; asymptotic P < .05). Conclusions and Relevance: This study found that NT-proBNP assay using minimal DBS samples appears to be timely and accurate in detecting CHD in newborns and to discriminate well between healthy newborns and newborns with various types of CHD. This finding warrants further studies in larger cohorts and highlights the potential of NT-proBNP to improve neonatal CHD screening.
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| 3. |
- Grevholm, Barbro, et al.
(författare)
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Lära och undervisa matematik : från förskoleklass till åk 6
- 2012
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Lära och undervisa matematik - från förskoleklass till åk 6 är en grundbok i matematik och matematikämnets didaktik. Den vänder sig till lärarstuderande och till verksamma lärare som vill aktualisera sina kunskaper och ta del av den senaste forskningen samt sätta sig in i de nya kursplanerna och kunskapskraven i matematik.
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| 4. |
- Noren, Elisabeth, et al.
(författare)
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Genetic variation and expression levels of tight junction genes identifies association between MAGI3 and inflammatory bowel disease
- 2017
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Ingår i: BMC Gastroenterology. - : BIOMED CENTRAL LTD. - 1471-230X. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: Inflammatory bowel disease (IBD) is associated with increased intestinal permeability, which involves paracellular passage regulated through tight junctions (TJ). The aim of the study was to investigate single nucleotide polymorphisms (SNP) located in genes encoding interacting TJ proteins and corresponding expressions, in relation to IBD. Methods: Allelic associations between TJ-related genes (F11R, MAGI1, MAGI2, MAGI3, PARD3, PTEN, and TJP1) and IBD, Crohns disease (CD), or ulcerative colitis (UC) were investigated. PTPN22 was included since its located in the same genetic region as MAGI3. Gene expression levels were investigated in relation to genotype, inflammatory status, phenotype, and medical treatment. Results: The two strongest allelic associations were observed between IBD and SNPs in MAGI2 (rs6962966) and MAGI3 (rs1343126). Another MAGI3 SNP marker (rs6689879) contributed to increased ileal MAGI3 expression level in non-IBD controls. Furthermore, association between inflammation and decreased expression levels of MAGI3, PTEN, and TJP1 in colonic IBD as well as UC mucosa, and between inflammation and increased expression of PTPN22 in colonic IBD mucosa, was observed. Conclusions: Our findings lend support to a genetic basis for modulation of intestinal epithelial barrier in IBD, and we have identified MAGI3 as a new candidate gene for IBD.
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| 5. |
- Noren, Elisabeth, et al.
(författare)
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Genetic Variation and Gene Expression Levels of Tight Junction Genes Indicates Relationships Between PTEN as well as MAGI1 and Microscopic Colitis
- 2018
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Ingår i: Digestive Diseases and Sciences. - : SPRINGER. - 0163-2116 .- 1573-2568. ; 63:1, s. 105-112
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Tidskriftsartikel (refereegranskat)abstract
- Microscopic colitis (MC) has been associated with increased paracellular permeability. Therefore, we aimed to investigate potential associations between MC and several genes encoding tight junction (TJ) proteins reported to interact with each other. The association between MC and single nucleotide polymorphisms (SNP; n = 63) within TJ genes (F11R, MAGI1, MAGI2, MAGI3, PARD3, PTEN, and TJP1) were investigated in a case-control study (n (MC patients) = 104 and n (controls) = 423). The genes that exhibited an association with MC were further investigated for gene expression related to genotype, MC phenotype, and gender using colonic biopsies from MC patients (n = 25) and controls (n = 58). Based on the number of investigated genes and after correction for multiple testing, an association was detected between a SNP marker in PTEN (rs1234224) and both MC overall (OR = 1.70, 95% CI 1.23-2.34, p = 0.001) and collagenous colitis (CC; OR = 1.79, 95% CI 1.22-2.62, p = 0.003). Further, SNP markers in MAGI1 (rs17417230) and F11R (rs790055) were associated with MC overall (OR = 1.58, 95% CI 1.14-2.19, p = 0.006) and with CC (OR = 2.58, 95% CI 1.27-5.25, p = 0.007), respectively. However, none of the associated SNPs contributed markedly to the expression of the respective genes. Nonetheless, decreased MAGI1 (p = 3.47 x 10(-4)) and PTEN (p = 0.004) expression was associated with lymphocytic colitis (LC) and CC, respectively, compared to controls. Decreased expression of PTEN and MAGI1 in the colonic mucosa might contribute to the pathogenesis of MC and its sub-phenotypes. Furthermore, our study indicates that genetic variants of TJ components are predisposing factors in the etiology of MC. Finally, F11R, MAGI1, and PTEN are new candidate genes that exhibit an association with MC.
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| 6. |
- Norén, Elisabeth
(författare)
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Genetic variation of tight junction structures in intestinal inflammation
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The epithelial barrier facing the external environment in the gastrointestinal (GI) tract is comprised of several components, including the tight junction (TJ) structures observed for the first time in 1963. TJ structures, which are multiprotein complexes composed of transmembrane proteins and a diverse spectrum of intracellular components, create a primary barrier to diffusion of ions, solutes, and water and they concomitantly prevent permeation of pro-inflammatory factors, such as pathogens, toxins, and antigens. Recent studies suggested that disturbance of epithelial integrity is associated with intestinal inflammatory conditions, such as inflammatory bowel disease (IBD), graft-versus-host disease (GVHD), celiac disease, but also diabetes. The general aim of this thesis was to identify novel genetic variants related to the development of intestinal inflammation with a specific focus on the TJ structures, yielding implications for epithelial integrity and paracellular permeability. Using a case-control study approach (Swedish cases and controls) in paper I, potential associations were investigated between IBD and three selected genetic markers in the genetic region of CLDN1, CLDN2, and CLDN4 (one marker per gene). The strongest association was observed between Crohn’s disease (CD) and the single nucleotide polymorphism (SNP) marker in the genetic region of CLDN2. The same SNP markers were further investigated using a family-based approach in non-Swedish families, but none of the identified associations from the Swedish case-control approach were confirmed. MORC4 which is located in the same genetic region as CLDN2 was also included in the investigation. A significant association was observed between a nonsynonymous SNP in MORC4 and CD in the Swedish case-control cohort. Similarities between IBD and GVHD include intestinal barrier defects and genetic contributions. GVHD is considered to be multifactorial, where the human leucocyte antigen (HLA) acts as a cornerstone; however, non-HLA genes have been identified in association with the outcome after stem cell transplantation (SCT). By using a casecontrol approach the relationship between non-HLA polymorphisms and emergence of GVHD as well as overall mortality after SCT was analyzed in paper II. The markers of MORC4, CD14, TLR4, and NOD2 were found to associate with the outcome (overall mortality) after SCT. The SNP marker of CD14 was the only analyzed marker that associated with acute GVHD. In paper III, the associations between IBD and several TJ genes that encode proteins reported to interact with each other were analyzed in a Swedish population. The strongest associations were observed between IBD and SNP markers in the membraneassociated guanylate kinase inverted genes MAGI2 and MAGI3. The MAGI3 SNP was also associated with ileal MAGI3 expression level in the non-inflamed non-IBD subgroup. Furthermore, no overlap between the expression levels of PTEN in inflamed colonic mucosa from patients with CD and those in the non-inflamed mucosa was detected, suggesting that PTEN is an inflammatory marker in CD. In paper IV, the genetic associations between microscopic colitis (MC) and TJ genes were analyzed in a Swedish population. The strongest association was identified between a SNP marker in PTEN and MC and also the sub-phenotype collagenous colitis (CC). Furthermore, significant associations were observed between genetic variations of MAGI1 and MC and also between a SNP marker in F11R and CC. Moreover, decreased expression levels of PTEN and MAGI1 were primarily associated to CC and the MC subtype lymphocytic colitis (LC), respectively, in comparison with controls. In conclusion, genes encoding proteins involved in the regulation of the intestinal epithelial integrity, including those contributing to TJ structures, may predispose individuals to intestinal inflammation, such as IBD and MC. Furthermore, MORC4 may be a predisposing factor for CD and one-year mortality after SCT for hematological malignancies.
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| 7. |
- Noren, Elisabeth, et al.
(författare)
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Single Nucleotide Polymorphisms in MORC4, CD14, and TLR4 Are Related to Outcome of Allogeneic Stem Cell Transplantation
- 2016
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Ingår i: Annals of Transplantation. - Warsaw, Poland : International Scientific Literature. - 1425-9524 .- 2329-0358. ; 21, s. 56-67
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Tidskriftsartikel (refereegranskat)abstract
- Background: Non-HLA genes may contribute to the prognosis after hematopoietic stem cell transplantation. We investigated associations between single nucleotide polymorphisms in regions of MORC4, CD14, TLR4, NOD2, SLC22A4, SLC22A5, CARD8, NLRP3, and CLDN2 and the outcomes of patients undergoing allogeneic stem cell transplantation. Material/Methods: Single nucleotide polymorphisms in selected regions were determined and analyzed for putative associations with overall mortality and acute graft-versus-host disease. Significant associations were further explored by logistic regression, controlling for additional variables. Results: A significant association was identified between overall mortality among recipients and a nonsynonymous coding variant of MORC4 (rs6622126) in the recipient genetic makeup (P=0.029). Since MORC4 is located on the X-chromosome, the results were also analyzed separately for males and females. The association between overall mortality for recipients and the risk allele (rs6622126; A) was confirmed for males with respect to genetic makeup of recipients (P=0.012), donor genetic makeup (P=0.004), and the combined allele composition of the donor and recipient (P=0.001). A significant association was also identified between overall mortality and the recipient risk allele of CD14 (rs2569190; P=0.031), TLR4 (rs4986790; P=0.043), and NOD2 (carriage of at least 1 mutant allele of rs2066844, rs2066845, or rs2066847; P=0.048). Among the investigated genes, only the CD14 (rs2569190) recipient risk allele was significantly associated with acute graft-versus-host disease (P=0.023). Logistic regression models confirmed these findings, except for NOD2, and also identified a significant contribution by age at stem cell transplantation (MORC4, CD14, TLR4), diagnosis (CD14, TLR4), and prophylaxis (MORC4). Conclusions: Genetic variation in MORC4, CD14, and TLR4 may affect the outcome of allogeneic stem cell transplantation.
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| 8. |
- Soderman, Jan, et al.
(författare)
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Analysis of single nucleotide polymorphisms in the region of CLDN2-MORC4 in relation to inflammatory bowel disease
- 2013
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Ingår i: World Journal of Gastroenterology. - : Baishideng Publishing Group Inc.. - 1007-9327 .- 2219-2840. ; 19:30, s. 4935-4943
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To investigate a possible genetic influence of claudin (CLDN) 1, CLDN2 and CLDN4 in the etiology of inflammatory bowel disease.METHODS: Allelic association between genetic regions of CLDN1, CLDN2 or CLDN4 and patients with inflammatory bowel disease, Crohn's disease (CD) or ulcerative colitis were investigated using both a case-control study approach (one case randomly selected from each of 191 Swedish inflammatory bowel disease families and 333 controls) and a family-based study (463 non-Swedish European inflammatory bowel disease-families). A nonsynonymous coding single nucleotide polymorphism in MORC4, located on the same linkage block as CLDN2, was investigated for association, as were two novel CLDN2 single nucleotide polymorphism markers, identified by resequencing.RESULTS: A single nucleotide polymorphism marker (rs12014762) located in the genetic region of CLDN2 was significantly associated to CD (case-control allelic OR = 1.98, 95% CI: 1.17-3.35, P = 0.007). MORC4 was present on the same linkage block as this CD marker. Using the case-control approach, a significant association (case control allelic OR = 1.61, 95% CI: 1.08-2.41, P = 0.018) was found between CD and a nonsynonymous coding single nucleotide polymorphism (rs6622126) in MORC4. The association between the CLDN2 marker and CD was not replicated in the family-based study. Ulcerative colitis was not associated to any of the single nucleotide polymorphism markers.CONCLUSION: These findings suggest that a variant of the CLDN2-MORC4 region predisposes to CD in a Swedish population.
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| 9. |
- Wadensten, Elisabeth, et al.
(författare)
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Diagnostic Yield From a Nationwide Implementation of Precision Medicine for all Children With Cancer.
- 2023
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Ingår i: JCO Precision Oncology (JCO PO). - : American Society of Clinical Oncology. - 2473-4284. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have indicated that broad genomic characterization of childhood cancer provides diagnostically and/or therapeutically relevant information in selected high-risk cases. However, the extent to which such characterization offers clinically actionable data in a prospective broadly inclusive setting remains largely unexplored.We implemented prospective whole-genome sequencing (WGS) of tumor and germline, complemented by whole-transcriptome sequencing (RNA-Seq) for all children diagnosed with a primary or relapsed solid malignancy in Sweden. Multidisciplinary molecular tumor boards were set up to integrate genomic data in the clinical decision process along with a medicolegal framework enabling secondary use of sequencing data for research purposes.During the study's first 14 months, 118 solid tumors from 117 patients were subjected to WGS, with complementary RNA-Seq for fusion gene detection in 52 tumors. There was no significant geographic bias in patient enrollment, and the included tumor types reflected the annual national incidence of pediatric solid tumor types. Of the 112 tumors with somatic mutations, 106 (95%) exhibited alterations with a clear clinical correlation. In 46 of 118 tumors (39%), sequencing only corroborated histopathological diagnoses, while in 59 cases (50%), it contributed to additional subclassification or detection of prognostic markers. Potential treatment targets were found in 31 patients (26%), most commonly ALK mutations/fusions (n = 4), RAS/RAF/MEK/ERK pathway mutations (n = 14), FGFR1 mutations/fusions (n = 5), IDH1 mutations (n = 2), and NTRK2 gene fusions (n = 2). In one patient, the tumor diagnosis was revised based on sequencing. Clinically relevant germline variants were detected in 8 of 94 patients (8.5%).Up-front, large-scale genomic characterization of pediatric solid malignancies provides diagnostically valuable data in the majority of patients also in a largely unselected cohort.
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| 10. |
- Wadensten, Elisabeth, et al.
(författare)
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Diagnostic Yield From a Nationwide Implementation of Precision Medicine for all Children With Cancer
- 2023
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Ingår i: JCO Precision Oncology. - : American Society of Clinical Oncology. - 2473-4284. ; :7
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Several studies have indicated that broad genomic characterization of childhood cancer provides diagnostically and/or therapeutically relevant information in selected high-risk cases. However, the extent to which such characterization offers clinically actionable data in a prospective broadly inclusive setting remains largely unexplored.Methods: We implemented prospective whole-genome sequencing (WGS) of tumor and germline, complemented by whole-transcriptome sequencing (RNA-Seq) for all children diagnosed with a primary or relapsed solid malignancy in Sweden. Multidisciplinary molecular tumor boards were set up to integrate genomic data in the clinical decision process along with a medicolegal framework enabling secondary use of sequencing data for research purposes.Results: During the study's first 14 months, 118 solid tumors from 117 patients were subjected to WGS, with complementary RNA-Seq for fusion gene detection in 52 tumors. There was no significant geographic bias in patient enrollment, and the included tumor types reflected the annual national incidence of pediatric solid tumor types. Of the 112 tumors with somatic mutations, 106 (95%) exhibited alterations with a clear clinical correlation. In 46 of 118 tumors (39%), sequencing only corroborated histopathological diagnoses, while in 59 cases (50%), it contributed to additional subclassification or detection of prognostic markers. Potential treatment targets were found in 31 patients (26%), most commonly ALK mutations/fusions (n = 4), RAS/RAF/MEK/ERK pathway mutations (n = 14), FGFR1 mutations/fusions (n = 5), IDH1 mutations (n = 2), and NTRK2 gene fusions (n = 2). In one patient, the tumor diagnosis was revised based on sequencing. Clinically relevant germline variants were detected in 8 of 94 patients (8.5%).Conclusion: Up-front, large-scale genomic characterization of pediatric solid malignancies provides diagnostically valuable data in the majority of patients also in a largely unselected cohort.
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