| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Blokland, G. A. M., et al.
(författare)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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| 4. |
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| 5. |
- Munn-Chernoff, M. A., et al.
(författare)
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Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies
- 2021
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Ingår i: Addiction Biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 26:1
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Tidskriftsartikel (refereegranskat)abstract
- Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [r(g)], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from similar to 2400 to similar to 537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (r(g) = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (r(g) = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (r(g) = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (r(gs) = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.
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| 6. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 7. |
- Bryois, J., et al.
(författare)
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Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease
- 2020
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:5, s. 482-493
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson’s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson’s disease. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
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| 8. |
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| 10. |
- Watson, H. J., et al.
(författare)
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Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa
- 2019
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:8
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Tidskriftsartikel (refereegranskat)abstract
- Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness(1), affecting 0.9-4% of women and 0.3% of men(2-4), with twin-based heritability estimates of 50-60%(5). Mortality rates are higher than those in other psychiatric disorders(6), and outcomes are unacceptably poor(7). Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)(8,9) and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.
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| 20. |
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| 21. |
- Watson, Hunna J., et al.
(författare)
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Common Genetic Variation and Age of Onset of Anorexia Nervosa
- 2022
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Ingår i: BIOLOGICAL PSYCHIATRY: GLOBAL OPEN SCIENCE. - : Elsevier BV. - 2667-1743. ; 2:4, s. 368-378
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche.METHODS: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (,13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses.RESULTS: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism-h2) were 0.01-0.04 for age of onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early-and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early -onset AN.CONCLUSIONS: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.
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| 26. |
- Angelison, Leif, et al.
(författare)
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Long-term outcome of infliximab treatment in chronic active ulcerative colitis : a Swedish multicentre study of 250 patients
- 2017
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley-Blackwell Publishing Inc.. - 0269-2813 .- 1365-2036. ; 45:4, s. 519-532
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Tidskriftsartikel (refereegranskat)abstract
- Background: Real-life long-term data on infliximab treatment in ulcerative colitis are limited.Aim: To study the long-term efficacy and safety of infliximab in chronic active ulcerative colitis and possible predictors of colectomy and response were also examined.Methods: A retrospective multi-centre study of infliximab treatment in 250 patients with chronic active ulcerative colitis with inclusion criteria: age ≥18 years, ambulatory treated, steroid-dependent or intolerant and/or immunomodulator refractory or intolerant.Results: Steroid-free clinical remission was achieved by 123/250 patients (49.2%) at 12 months and in 126/250 patients at a median follow-up of 2.9 years (50.4%). Primary response at 3 months was achieved by 190/250 (76.0%) patients and associated with a high probability of response 168/190 (88.4%) at 12 months and 143/190 (75.3%) at follow-up. Long-term rate of colectomy in primary responders was 6/190 (3.2%) at 12 months and 27/190 (14.2%) at last follow-up. Failure to achieve response at 3 months was associated with a high risk of subsequent colectomy, 29/60 (48.3%) at 12 months and 41/60 (68.3%) at follow-up. Response at 12 months was associated with a low risk of subsequent colectomy, 14/181 (7.7%) compared with non-response 19/34 (55.9%) (P < 0.0001). Non-response at 3 months was an independent predictor of subsequent colectomy (HR = 9.40, 95% CI = 5.10-17.35, P < 0.001). Concomitant azathioprine therapy did not influence outcome in terms of colectomy.Conclusions: Long-term efficacy of infliximab treatment in chronic active ulcerative colitis is excellent especially in patients who respond to induction treatment. Conversely, non-response at 3 months predicts a poor outcome, with a high risk of subsequent colectomy.
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| 27. |
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| 28. |
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| 29. |
- Jorgensen, F S, et al.
(författare)
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MULTISCAN--a Scandinavian multicenter second trimester obstetric ultrasound and serum screening study
- 1999
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - 1600-0412. ; 78:6, s. 501-510
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To study the detection rates of second trimester ultrasound screening for neural tube defects (NTD), abdominal wall defects (AWD) and Down's syndrome (DS) in low risk populations at tertiary centers, and to compare the ultrasound screening detection rates with those that were obtainable by biochemical serum screening (double test: alpha-fetoprotein/human chorion gonadotrophin/age test). STUDY DESIGN: Prospective multicenter study with a three year inclusion period: 1/1/1989-31/12/1991. SUBJECTS: 27,844 low-risk women at 18-34 years of age who had a second trimester ultrasound screening examination. Of these, 10,264 also had a serum test. METHODS: An ultrasound malformation scan and a serum test were carried out at 17-19 weeks of gestation. Risk calculations regarding DS were based on alpha-fetoprotein, human chorion gonadotrophin and maternal age; performed retrospectively for the first two years. RESULTS: In total 73 cases were identified in the study population: NTD (n=34), AWD (n=7) and DS (n=32). The detection rates, (%, with 95% confidence interval) for ultrasound screening were: NTD: 79.4 (62.1-91.3); AWD: 85.7 (42.1-99.6); DS: 6.3 (0.8-20.8). In the subgroup of women who had both tests, the detection rates for ultrasound screening vs double test were: NTD: 62.5 (24.5-91.5) vs 75.0 (34.9-96.8); AWD: 66.7 (9.4-99.2) vs 100 (29.2-100.0); DS: 7.7 (0.2-36.0) vs 46.2 (19.2-74.9). The false positive rates (%) for ultrasound screening vs double test were: NTD: 0.01/3.3; AWD: 0.01/3.3; DS: 0.1/4.0. CONCLUSION: Second trimester ultrasound screening in a low risk population gave a low detection rate for fetal DS (6.3%) and an acceptable detection rate for NTD (79.4%) and AWD (85.7%). In the subgroup of women who had both tests, serum screening performed better than ultrasound as applied in the present study, especially regarding DS.
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| 30. |
- Nyberg, L., et al.
(författare)
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Observational study of tofacitinib in ulcerative colitis in Sweden (ODEN) - Interim analysis of clinical and biomarker data
- 2024
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Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 18:Suppl. 1, s. I1703-I1704
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Tofacitinib is a Janus kinase (JAK) inhibitor for the treatment of moderate to severe ulcerative colitis (UC). ODEN is an ongoing Swedish multicentre prospective observational study regarding effectiveness of tofacitinib in UC. In this interim analysis, we aimed to assess the clinical outcomes during the first 16 weeks.Methods: Patients with active UC were enrolled 2020-2023 when starting tofacitinib as per clinical indication. Inclusion criteria were fecal (F) calprotectin >250 mg/kg or Mayo endoscopic score ≥2. Data were collected using an electronic case report form linked to the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG). Data concerning inflammatory markers, endoscopic activity, partial (p) Mayo, extra intestinal manifestations, health-related quality of life measures, corticosteroid use, and colectomy rates were collected regardless of tofacitinib discontinuation. Information collected at week 8 and 16 is presented here. Intention-to-treat (ITT) analysis was applied and tofacitinib discontinuation was considered as treatment failure (i.e., no tofacitinib-induced clinical or laboratory response or remission). McNemar’s test was used for proportion differences.Results: The proportion of patients who previously had failed at least one biologic was 95% and at least two biologics, 62%. At inclusion, median p-Mayo was 5 and 39% of patients were on corticosteroids (Table 1a). Patients’ survival on drug is shown in Figure 1a. At week 8 and 16, 42% and 43%, respectively, achieved corticosteroid free clinical remission, Figure 1b. A 50% reduction in F-calprotectin was seen in 54% and 49% at week 8 and 16, respectively. The endpoint of Mayo endoscopic score 0 and/or F-calprotectin <100 mg/kg was achieved by 30% and 38% at week 8 and 16, respectively. Arthralgia frequency decreased significantly from baseline from 29% at inclusion to 13% and 11% at week 8 and 16 respectively. Three patients underwent colectomy the first 16 weeks (Table 1b).Conclusion: After 16 weeks of treatment with tofacitinib, a substantial proportion of previously treatment refractory UC patients were in clinical and endoscopic corticosteroid-free remission, and a distinct improvement in F-calprotectin levels was observed. In addition, a significant reduction in arthralgia was noted.
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| 31. |
- Nyberg, L., et al.
(författare)
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Observational study of tofacitinib in Ulcerative Colitis in Sweden (ODEN) - Interim analysis of health-related quality of life and fatigue
- 2024
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Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 18:Suppl. 1, s. I1887-I1889
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Ulcerative colitis (UC) has a major impact on daily life. The Janus Kinas (JAK) inhibitor tofacitinib is effective in achieving remission in UC, but prospective real-world evidence concerning the effect on health-related quality of life (HRQoL) and fatigue are still scarce. Fatigue is a component of UC that is notoriously difficult to treat and not unambiguously related to inflammatory activity. ODEN is an ongoing Swedish multicentre prospective observational study of tofacitinib in UC. In this interim analysis, we assessed the effectiveness on HRQoL and fatigue during the first 16 weeks.Methods: Patients with UC and active inflammation were enrolled 2020-2023 when starting tofacitinib as per clinical indication. To measure various aspects of impairment of daily life, the validated questionnaires Short Health Scale (SHS), EQ-5D-5L [Swedish value set], and IBD-fatigue scale (IBD-F) were used. These data and information concerning clinical, biochemical, and endoscopic outcomes were collected in an e-CRF linked to the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG). For HRQoL outcomes, per protocol analysis was applied. Paired t-test and Wilcoxon’s signed-rank test were used for mean and median differences, respectively.Results: In total, 103 patients were included. Baseline data are shown in Table 1a. For patients still on tofacitinib treatment, all four dimensions of the SHS (symptoms, social function, disease related worry, and general well-being) improved significantly, Table 1b. A median decrease of one point from baseline was seen at week 8 in each of the parameters, which was maintained through week 16 with a tendency towards further improvement. EQ-5D-5L showed an impairment mainly in the aspects of pain/discomfort and ability to participate in common daily activities. Improvement in these dimensions was seen from baseline to week 16. The overall EQ-5D-5L index improved significantly from baseline (0.80) to week 8 (0.86) and week 16 (0.89), as did the EQ VAS 0-100 reflecting overall health (58, 71, and 74, respectively). A significant improvement in IBD-F part 1 and 2 was seen at week 8 and 16, Figure 1.Conclusion: This study demonstrates that tofacitinib treatment covariates with positive changes in a variety of measures of patients’ quality of life, including improvements in self-assessed overall wellbeing. Finally, fatigue significantly improved during tofacitinib treatment. Thus, tofacitinib treatment shows association with meaningful improvements in multiple aspects of quality of life during the first 16 weeks of treatment.
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| 32. |
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| 33. |
- Schon, M P, et al.
(författare)
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Mucosal T lymphocyte numbers are selectively reduced in integrin alpha E (CD103)-deficient mice
- 1999
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Ingår i: Journal of Immunology. - 1550-6606. ; 162:11, s. 6641-6649
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Tidskriftsartikel (refereegranskat)abstract
- The mucosal lymphocyte integrin alpha E(CD103)beta 7 is thought to be important for intraepithelial lymphocyte (IEL) localization or function. We cloned the murine integrin gene encoding alpha E, localized it to chromosome 11, and generated integrin alpha E-deficient mice. In alpha E-/- mice, intestinal and vaginal IEL numbers were reduced, consistent with the known binding of alpha E beta 7 to E-cadherin expressed on epithelial cells. However, it was surprising that lamina propria T lymphocyte numbers were diminished, as E-cadherin is not expressed in the lamina propria. In contrast, peribronchial, intrapulmonary, Peyer's patch, and splenic T lymphocyte numbers were not reduced in alpha E-deficient mice. Thus, alpha E beta 7 was important for generating or maintaining the gut and vaginal T lymphocytes located diffusely within the epithelium or lamina propria but not for generating the gut-associated organized lymphoid tissues. Finally, the impact of alpha E deficiency upon intestinal IEL numbers was greater at 3-4 wk of life than in younger animals, and affected the TCR alpha beta+ CD8+ T cells more than the gamma delta T cells or the TCR alpha beta+ CD4+CD8- population. These findings suggest that alpha E beta 7 is involved in the expansion/recruitment of TCR alpha beta+ CD8+ IEL following microbial colonization. Integrin alpha E-deficient mice will provide an important tool for studying the role of alpha E beta 7 and of alpha E beta 7-expressing mucosal T lymphocytes in vivo.
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| 34. |
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| 35. |
- Grankvist, Anna, et al.
(författare)
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Multilocus sequence analysis of clinical "candidatus neoehrlichia mikurensis" strains from Europe
- 2015
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Ingår i: Journal of Clinical Microbiology. - 0095-1137 .- 1098-660X. ; 53:10, s. 3126-3132
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Tidskriftsartikel (refereegranskat)abstract
- Copyright © 2015, American Society for Microbiology. All Rights Reserved. Candidatus Neoehrlichia mikurensis" is the tick-borne agent of neoehrlichiosis, an infectious disease that primarily affects immunocompromised patients. So far, the genetic variability of "Ca. Neoehrlichia" has been studied only by comparing 16S rRNA genes and groEL operon sequences. We describe the development and use of a multilocus sequence analysis (MLSA) protocol to characterize the genetic diversity of clinical "Ca. Neoehrlichia" strains in Europe and their relatedness to other species within the Anaplasmataceae family. Six genes were selected: ftsZ, clpB, gatB, lipA, groEL, and 16S rRNA. Each MLSA locus was amplified by real-time PCR, and the PCR products were sequenced. Phylogenetic trees of MLSA locus relatedness were constructed from aligned sequences. Blood samples from 12 patients with confirmed "Ca. Neoehrlichia" infection from Sweden (n9), the Czech Republic (n2), and Germany (n1) were analyzed with the MLSA protocol. Three of the Swedish strains exhibited identical lipA sequences, while the lipA sequences of the strains from the other nine patients were identical to each other. One of the Czech strains had one differing nucleotide in the clpB sequence from the sequences of the other 11 strains. All 12 strains had identical sequences for the genes 16S rRNA, ftsZ, gatB, and groEL. According to the MLSA, among the Anaplasmataceae, "Ca. Neoehrlichia" is most closely related to Ehrlichia ruminantium, less so to Anaplasma phagocytophilum, and least to Wolbachia endosymbionts. To conclude, three sequence types of infectious "Ca. Neoehrlichia" were identified: one in the west of Sweden, one in the Czech Republic, and one spread throughout Europe.
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| 36. |
- Hansson, Stefan, et al.
(författare)
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Gene expression profiling of human placentas from preeclamptic and normotensive pregnancies.
- 2006
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Ingår i: Molecular Human Reproduction. - : Oxford University Press (OUP). - 1460-2407. ; 12:3, s. 169-179
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate patterns of gene expression in placental samples from patients with preeclampsia (PE), persistent bilateral uterine artery notching (without PE), and normal controls. This study included placental tissue from nine women with PE, seven with uncomplicated pregnancies and five with bilateral uterine artery notching in Doppler velocimetry tracings. Human cDNA microarrays with 6500 transcripts/genes were used and the results verified with real-time PCR and in-situ hybridization. Multidimensional scaling method and random permutation technique demonstrated significant differences among the three groups examined. Within the 6.5K arrays, 6198 elements were unique cDNA clones representing 5952 unique UniGenes and 5695 unique LocusLinks. Multidimensional scaling plots showed 5000 genes that met our quality criteria; among these, 366 genes were significantly different in at least one comparison. Differences in three genes of interest were confirmed with real-time PCR and in-situ hybridization; acid phosphatase 5 was shown to be overexpressed in PE samples and calmodulin 2 and v-rel reticuloendotheliosis viral oncogene homolog A (RELA) were downregulated in PE and uterine artery notch placentas. In conclusion downregulation of RELA and calmodulin 2 might represent an attempt by the placenta to compensate for elevations in intracellular calcium, possibly caused by hypoxia and/or apoptosis, in both pregnancies with uterine artery notching and preeclampsia.
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| 37. |
- Moutquin, J.M., et al.
(författare)
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Effectiveness and safety of the oxytocin antagonist atosiban versus beta-adrenergic agonists in the treatment of preterm labour
- 2001
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Ingår i: British Journal of Obstetrics and Gynaecology. - : Wiley. - 1365-215X .- 1470-0328 .- 1471-0528. ; 108:2, s. 133-142
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Tidskriftsartikel (refereegranskat)abstract
- Objective To compare the effectiveness and safety of the oxytocin antagonist atosiban with conventional beta-adrenergic agonist (beta-agonist) therapy in the treatment of preterm labour. Design Three multinational, multicentre, double-blind, randomised, controlled trials. Setting Hospitals in Australia, Canada, Czech Republic, Denmark, France, Israel, Sweden, and the UK. Population Women diagnosed with preterm labour at 23-33 completed weeks of gestation. Methods Seven hundred and forty-two women were randomised; 733 received atosiban (n = 363; intravenous (iv) bolus dose of 6.75 mg, then 300 mug/minute iv. for 3h and 100 mug/min iv thereafter) or beta-agonist (n 379; ritodrine, salbutamol or terbutaline iv; dose titrated) for at least 18h and rip to 48 hours. Uterine contraction rate, cervical dilatation and effacement were used to assess progression of labour. An all patients treated analysis, using the Cochran-Mantel-Haenszel test, was performed. Main outcome measures Tocolytic effectiveness was assessed in terms of the number of women undelivered after 48 hours and seven days. Safety was assessed in terms of maternal side effects and neonatal morbidity. Results There were no significant differences between atosiban and beta -agonists in delaying delivery for 48h (88.1% vs 88.9%; P = 0.99) or seven days (79.7% versus 77.6%; P = 0.28). Tocolytic effectiveness was also similar in terms of mean [SD] gestational age at delivery (35.8 [3.9] weeks vs 35.5 [4.1] weeks) and mean [SD] birthweight (2491 [813] g versus 2461 [831] g). Maternal side effects, particularly cardiovascular adverse events (8.3% vs 81.2%, P < 0.001) were reported more frequently in women given beta -agonists, resulting in more treatment discontinuations due to side effects (1.1% vs 15.4%, P = 0.0001). No statistical differences in neonatal/infant outcomes were observed with either study medication. Conclusions In the largest study of tocolytic therapy to date, atosiban was comparable in clinical effectiveness to conventional beta-agonist therapy, but was associated with fewer maternal cardiovascular side effects. We conclude that atosiban has clinical advantages over current tocolytic therapy.
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| 40. |
- Salomon, Benita, 1993-, et al.
(författare)
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Prognostic potential of mucosal proteins in Ulcerative Colitis
- 2024
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Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 18:Suppl. 1, s. I544-I545
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Better prognostic measures for ulcerative colitis (UC) could significantly advance patient care. While the prognostic capacity of circulating proteins in UC has been explored, the role of mucosal proteins remains largely unknown. We examined mucosal protein markers in patients with incident ulcerative colitis and evaluated their prognostic value.Methods: Biopsies from macroscopically inflamed colonic/rectal mucosa of adult patients in the Swedish inception cohort of IBD (SIC IBD) were obtained at diagnosis of UC. Patients were followed prospectively, and clinical data were recorded after 3 and 12 months. Disease course was categorised as indolent or aggressive at 12 months, based on a composite outcome of colectomy, hospital admission for active disease, treatment refractoriness towards ≥2 biological agents; the use of >2 courses of corticosteroids, or a cumulative dose of >2.5 g. Relative estimates of 162 protein markers were assessed in homogenised tissue supernatants, using proximity extension assay technology (Olink Proteomics, Uppsala, Inflammation and Oncology II panel). Mann-Whitney U test, with Benjamini-Hochberg correction was used to identify differentially regulated mucosal proteins in aggressive vs indolent disease course, with a 5% false discovery rate (FDR). Smoothly clipped absolute deviation regularised logistic regression models were used to identify prognostic signatures distinguishing aggressive from indolent disease course. Performance was estimated in a leave-one-out cross-validation and reported as the area under the receiver operating characteristic (ROC) curve (AUC).Results: 117 patients provided a macroscopically inflamed colonic/rectal biopsy at diagnosis of UC. Basic demographics and clinical characteristics are presented in Table 1. Relative protein levels of WFdc2 and CCL20 were significantly lower in lysates from patients developing an aggressive course vs patients developing an indolent course, while estimates of MMP1, CCL11, WISP-1, OPG, RSPO3 and VEGFR2 were higher (Figure 1A). Regularized logistic regression identified signatures restricted to 28 proteins, distinguishing aggressive from indolent UC courses, yielding an AUC of 0.68 (95% confidence interval (CI): 0.56-0.80) for left-out samples (Figure 1B). Incorporating extent of inflammation at diagnosis in the model improved the AUC to 0.71 (95% CI: 0.60-0.83).Conclusion: We identified prognostic mucosal protein signatures associated with future course of ulcerative colitis by analysing inflamed mucosal biopsies that were obtained at diagnosis. These protein markers may highlight pathways of relevance for ulcerative colitis outcomes.
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| 43. |
- Zeitlin, J.A., et al.
(författare)
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Marital status, cohabitation, and the risk of preterm birth in Europe: where births outside marriage are common and uncommon.
- 2002
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Ingår i: Paediatric and Perinatal Epidemiology. - : Wiley. - 0269-5022 .- 1365-3016. ; 16:2, s. 124-130
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Tidskriftsartikel (refereegranskat)abstract
- This article explores whether the impact of marital status on the risk of preterm birth varies in relation to marital practices in the population, defined by the proportion of out-of-marriage births. Data come from a case–control study of the determinants of preterm birth in 16 European countries (5456 cases and 8234 controls). There is a significantly elevated risk of preterm birth associated with both cohabitation (OR = 1.29 [1.08, 1.55]) and single motherhood (OR = 1.61 [1.26, 2.07]) for women living in countries where fewer than 20% of births occur outside marriage. In contrast, there is no excess risk associated with marital status when out-of-marriage births are more common. This overall result does not apply to all subgroups of preterm births: different patterns emerge for early preterm births and preterm births induced for medical reasons. It is important to consider social context in the analysis of individual risk factors.
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| 44. |
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| 45. |
- Abramowicz, Jacques S., et al.
(författare)
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Guidelines for Cleaning Transvaginal Ultrasound Transducers Between Patients
- 2017
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Ingår i: Ultrasound in Medicine and Biology. - : Elsevier BV. - 0301-5629. ; 43:5, s. 1076-1079
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this article is to provide guidance regarding the cleaning and disinfection of transvaginal ultrasound probes. These recommendations are also applicable to transrectal probes.
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| 46. |
- Ayres-de-Campos, D, et al.
(författare)
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Can the reproducibility of fetal heart rate baseline estimation be improved?
- 2004
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Ingår i: European Journal of Obstetrics, Gynecology, and Reproductive Biology. - 0301-2115. ; 112:1, s. 49-54
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the reproducibility of fetal heart rate (FHR) baseline estimation according to an objective and detailed definition presented in this article, by comparison with the FIGO guidelines' definition. Study design: Three hundred consecutively acquired FHR tracings, 150 from antepartum high-risk pregnancies and 150 from unselected intrapartum cases, were presented to nine experienced clinicians included in three different groups, for an estimation of the FHR baseline. The first group consisted of clinicians using the proposed definition, without previous training in its use. The second group consisted of clinicians using the proposed definition, where a previous training session was promoted. The third group consisted of clinicians using the FIGO guidelines' definition. Agreement in baseline estimation was evaluated using the kappa statistic, the proportions of agreement and the intra-class correlation coefficient. Results: Using the baseline definition proposed in this article, agreement was significantly higher in the group with prior training in its use. This group also showed a trend towards a higher agreement than the one using the FIGO guidelines. Conclusion: The FHR baseline definition proposed in this article provides an extremely reproducible estimation when associated with prior training in its use.
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| 47. |
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| 48. |
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| 49. |
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| 50. |
- Granqvist, Claes Göran, et al.
(författare)
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Electrochromic foil-based devices : Optical transmittance and modulation range, effect of ultravioled irradiation, and quality assessment by 1/f current noise
- 2008
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Ingår i: Thin Solid Films. - : Elsevier BV. - 0040-6090 .- 1879-2731. ; 516:17, s. 5921-5926
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Tidskriftsartikel (refereegranskat)abstract
- We introduce electrochromic (EC) technology for modulating the transmittance of visible light and solar radiation in window apertures, with focus on recent work on foil-type devices embodying sputter deposited WO3 and NiO films joined by a polymer electrolyte. The purpose of this paper is to present a number of new and preliminary results showing that (i) double-sided antireflection coatings based on dip coating can enhance the transmittance significantly, (ii) tandem foils can yield a ratio between bleached-state and colored-state transmittance exceeding fifty, (iii) solar irradiance onto the EC device can enhance its charge insertion dynamics and thereby its optical modulation, and (iv) electromagnetic noise spectroscopy may serve as quality assessment of EC devices.
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