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| 2. |
- Middeldorp, Christel M., et al.
(författare)
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The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
- 2019
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
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Tidskriftsartikel (refereegranskat)abstract
- The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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| 3. |
- Gerkin, Richard C., et al.
(författare)
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Recent Smell Loss Is the Best Predictor of COVID-19 Among Individuals With Recent Respiratory Symptoms
- 2021
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Ingår i: Chemical Senses. - : Oxford University Press (OUP). - 0379-864X .- 1464-3553. ; 46
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Tidskriftsartikel (refereegranskat)abstract
- In a preregistered, cross-sectional study, we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0–100 visual analog scales (VAS) for participants reporting a positive (C19+; n = 4148) or negative (C19−; n = 546) COVID-19 laboratory test outcome. Logistic regression models identified univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery. Both C19+ and C19− groups exhibited smell loss, but it was significantly larger in C19+ participants (mean ± SD, C19+: −82.5 ± 27.2 points; C19−: −59.8 ± 37.7). Smell loss during illness was the best predictor of COVID-19 in both univariate and multivariate models (ROC AUC = 0.72). Additional variables provide negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms (e.g., fever). Olfactory recovery within 40 days of respiratory symptom onset was reported for ~50% of participants and was best predicted by time since respiratory symptom onset. We find that quantified smell loss is the best predictor of COVID-19 amongst those with symptoms of respiratory illness. To aid clinicians and contact tracers in identifying individuals with a high likelihood of having COVID-19, we propose a novel 0–10 scale to screen for recent olfactory loss, the ODoR-19. We find that numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4 < OR < 10). Once independently validated, this tool could be deployed when viral lab tests are impractical or unavailable.
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| 8. |
- Bedri, SK, et al.
(författare)
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From Genetic Variations to Biomarkers
- 2014
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Ingår i: SCANDINAVIAN JOURNAL OF IMMUNOLOGY. - 0300-9475. ; 79:6, s. 477-477
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 14. |
- Fiessinger, J. N., et al.
(författare)
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Ximelagatran vs low-molecular-weight heparin and warfarin for the treatment of deep vein thrombosis: a randomized trial
- 2005
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Ingår i: Jama. - 1538-3598. ; 293:6, s. 681-9
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Ximelagatran, an oral direct thrombin inhibitor with a rapid onset of action and predictable antithrombotic effect, has the potential to be a simple therapeutic alternative to current standard treatment of acute venous thromboembolism. OBJECTIVE: To compare the efficacy and safety of ximelagatran with standard enoxaparin/warfarin treatment for the prevention of recurrent venous thromboembolism. DESIGN, SETTING, AND PATIENTS: Randomized, double-blind, noninferiority trial (Thrombin Inhibitor in Venous Thromboembolism [THRIVE] Treatment Study) of 2489 patients with acute deep vein thrombosis, of whom approximately one third had concomitant pulmonary embolism. The study was conducted at 279 centers in 28 countries from September 2000 through December 2002. INTERVENTIONS: Patients were randomized to receive 6 months of treatment with either oral ximelagatran, 36 mg twice daily, or subcutaneous enoxaparin, 1 mg/kg twice daily, for 5 to 20 days followed by warfarin adjusted to maintain an international normalized ratio of 2.0 to 3.0. MAIN OUTCOME MEASURES: Recurrent venous thromboembolism, bleeding, and mortality. RESULTS: Venous thromboembolism recurred in 26 of the 1240 patients assigned to receive ximelagatran (estimated cumulative risk, 2.1%) and in 24 of the 1249 patients assigned to receive enoxaparin/warfarin (2.0%). The absolute difference between ximelagatran and enoxaparin/warfarin was 0.2% (95% confidence interval [CI], -1.0% to 1.3%). This met the prespecified criterion for noninferiority. Corresponding values for major bleeding were 1.3% and 2.2% (difference, -1.0%; 95% CI, -2.1% to 0.1%), and for mortality were 2.3% and 3.4% (difference, -1.1%; 95% CI, -2.4% to 0.2%). Alanine aminotransferase levels increased to more than 3 times the upper limit of normal in 119 patients (9.6%) and 25 patients (2.0%) receiving ximelagatran and enoxaparin/warfarin, respectively. Increased enzyme levels were mainly asymptomatic. Retrospective analysis of locally reported adverse events showed a higher rate of serious coronary events with ximelagatran (10/1240 patients) compared with enoxaparin/warfarin (1/1249 patients). CONCLUSIONS: Oral ximelagatran administered in a fixed dose without coagulation monitoring, was as effective as enoxaparin/warfarin for treatment of deep vein thrombosis with or without pulmonary embolism and showed similar, low rates of bleeding. Increased levels of liver enzymes in 9.6% of ximelagatran-treated patients require regular monitoring; the mechanism requires further evaluation. Prospective assessment of coronary events in future studies is warranted.
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| 15. |
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| 16. |
- Hassan, Sk Sarif, et al.
(författare)
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A unique view of SARS-CoV-2 through the lens of ORF8 protein
- 2021
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Ingår i: Computers in Biology and Medicine. - : Elsevier BV. - 0010-4825 .- 1879-0534. ; 133
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Tidskriftsartikel (refereegranskat)abstract
- Immune evasion is one of the unique characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attributed to its ORF8 protein. This protein modulates the adaptive host immunity through down regulation of MHC-1 (Major Histocompatibility Complex) molecules and innate immune responses by surpassing the host's interferon-mediated antiviral response. To understand the host's immune perspective in reference to the ORF8 protein, a comprehensive study of the ORF8 protein and mutations possessed by it have been performed. Chemical and structural properties of ORF8 proteins from different hosts, such as human, bat, and pangolin, suggest that the ORF8 of SARS-CoV-2 is much closer to ORF8 of Bat RaTG13-CoV than to that of Pangolin-CoV. Eighty-seven mutations across unique variants of ORF8 in SARS-CoV-2 can be grouped into four classes based on their predicted effects (Hussain et al., 2021) [1]. Based on the geo-locations and timescale of sample collection, a possible flow of mutations was built. Furthermore, conclusive flows of amalgamation of mutations were found upon sequence similarity analyses and consideration of the amino acid conservation phylogenies. Therefore, this study seeks to highlight the uniqueness of the rapidly evolving SARS-CoV-2 through the ORF8.
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| 21. |
- Jonsson, S W, et al.
(författare)
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Increased prevalence of atherosclerosis in patients with medium term rheumatoid arthritis
- 2001
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Ingår i: Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 28, s. 2597-2602
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To measure the extent of atherosclerosis in patients with rheumatoid arthritis (RA) with a disease duration of considerable length, and in age and sex matched individuals. Methods. Thirty-nine patients with RA (30 women, 9 men) with disease onset occurring between 1974 and 1978, and less than 65 years of age at the time of investigation, were enrolled together with 39 sex and age matched controls. Quantitative measurement of intima-media thickness (IMT) and semiquantitative assessment of the presence of plaque were undertaken by B-mode ultrasound of the common carotid artery (CCA-IMT) and the common femoral artery on the right-hand side. Echo Doppler cardiography was performed with an Accuson Aspen. The results were related to disease activity variables and accumulated disease activity, to lipid levels [i.e., cholesterol, high density lipoproteins, low density lipoproteins, triglycerides (TG)], to hemostatic factors [tissue plasminogen activator antigen (tPAag), plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF)], and to soluble adhesion molecules (sICAM-1 and sE-selectin). Results. Patients with RA had higher maximal and mean IMT values compared with controls. The difference concerning mean CCA-IMT reached statistical significance in patients with RA and correlated significantly with lipids (cholesterol, LDL, LDL/HDL ratio, TG) and tPAag. The prevalence of plaques, as well as of aortic cusp sclerosis, was higher in RA but only the difference in aortic cusp sclerosis was statistically significant. Patients with plaques had significantly higher levels of lipids (cholesterol, LDL, LDL/HDL ratio) than patients without plaques, while patients with cusp sclerosis had significantly higher cholesterol and TG levels. sICAM-1 was significantly higher both in patients with plaques and in those with aortic cusp sclerosis compared to patients without. Conclusion. Our results suggest an accelerated atherosclerosis in patients with RA that is related mainly to lipid levels.
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| 23. |
- Lundstrom, M, et al.
(författare)
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Strategy to reduce the number of patients perceiving impaired visual function after cataract surgery
- 2002
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Ingår i: Journal of Cataract and Refractive Surgery. - 1873-4502. ; 28:6, s. 971-976
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To reduce the number of patients who perceive more difficulties performing daily life activities 6 months after cataract extraction than before surgery. Setting: Surgeons at 4 surgical units participating in the yearly outcome studies organized by the Swedish National Cataract Register. Methods: This study comprised surgical outcomes data and completed Catquest results before and after surgery collected from consecutive patients during a 1-month period yearly since 1995. The reasons for a no-benefit outcome from 1995 to 1997 were identified. During the 1-month study period in 1999, a strategy was launched to reduce postoperative anisometropia and disturbances from cataract in the fellow eye through better surgical planning. Results: The percentage of patients with a no-benefit outcome who had anisometropia or cataract in the fellow eye as a probable reason for the outcome decreased from 27.3% and 13.0%, respectively, in the 1995 to 1997 study to 10.5% and 10.5%, respectively, in the 1999 study. Other reasons for a no-benefit outcome such as ocular co-morbidity or few preoperative problems increased in frequency, presumably as a result of a change in case mix. Conclusions: A strategy to reduce the number of patients perceiving more difficulties in performing daily life activities after cataract extraction than before surgery was tested, The number of patients with reasons for a poor outcome that the study focused on was reduced. Patients who gave reasons for a poor outcome other than anisometropia or cataract in the fellow eye increased in frequency, probably as a result of a change in case mix.
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| 24. |
- Lundstrom, UH, et al.
(författare)
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Barriers and opportunities to increase PD incidence and prevalence: Lessons from a European Survey
- 2021
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Ingår i: Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. - : SAGE Publications. - 1718-4304 .- 0896-8608. ; 41:6, s. 542-551
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Tidskriftsartikel (refereegranskat)abstract
- Peritoneal dialysis (PD) remains underutilised and unplanned start of dialysis further diminishes the likelihood of patients starting on PD, although outcomes are equal to haemodialysis (HD). Methods: A survey was sent to members of EuroPD and regional societies presenting a case vignette of a 48-year-old woman not previously known to the nephrology department and who arrives at the emergency department with established end-stage kidney disease (unplanned start), asking which dialysis modality would most likely be chosen at their respective centre. We assessed associations between the modality choices for this case vignette and centre characteristics and PD-related practices. Results: Of 575 respondents, 32.8%, 32.2% and 35.0% indicated they would start unplanned PD, unplanned HD or unplanned HD with intention to educate patient on PD later, respectively. Likelihood for unplanned start of PD was only associated with quality of structure of the pre-dialysis program. Structure of pre-dialysis education program, PD program in general, likelihood to provide education on PD to unplanned starters, good collaboration with the PD access team and taking initiatives to enhance home-based therapies increased the likelihood unplanned patients would end up on PD. Conclusions: Well-structured pre-dialysis education on PD as a modality, good connections to dedicated PD catheter placement teams and additional initiatives to enhance home-based therapies are key to grow PD programs. Centres motivated to grow their PD programs seem to find solutions to do so.
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| 25. |
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| 26. |
- Lundstrom, W, et al.
(författare)
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Interferon beta treatment of multiple sclerosis increases serum interleukin-7
- 2014
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 20:13, s. 1727-1736
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin-7 (IL-7) is a non-redundant cytokine for T-cell development and survival. The IL-7 signaling pathway has been genetically and functionally associated with several autoimmune diseases including multiple sclerosis (MS). Objective: The objective of this paper is to elucidate the effect of the widely used immunomodulatory MS therapy interferon beta (IFNβ) on IL-7 homeostasis. Methods: Swedish MS patients were screened for IL-7 concentration in serum and blood cell counts. IL-7 receptor alpha chain (IL-7Rα) expression was determined by semi-quantitative real-time polymerase chain reaction (PCR) and flow cytometry. Results: IFNβ treatment led to significantly increased serum IL-7 levels (mean: 17 pg/ml) compared with healthy controls (mean: 7.6 pg/ml) and natalizumab-treated patients (mean: 5.3 pg/ml). In vitro and in vivo, peripheral blood leukocytes showed decreased IL-7Rα expression and IL-7 consumption upon IFNβ exposure, suggesting that their IL-7 responsiveness is impaired during treatment. Conclusions: MS patients undergoing IFNβ treatment have increased serum IL-7 levels and decreased IL-7 consumption. Given IL-7’s important role in T-cell immunity, this relationship may be highly relevant for IFNβ’s treatment efficacy.
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| 28. |
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| 29. |
- Lundstrom, W, et al.
(författare)
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Soluble IL7Rα potentiates IL-7 bioactivity and promotes autoimmunity
- 2013
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 110:19, s. E1761-E1770
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Tidskriftsartikel (refereegranskat)abstract
- Many genes have been shown to influence the risk of developing multiple sclerosis (MS); however, the biological processes responsible are not clear. We found that a genetic polymorphism associated with increased MS risk is responsible for potentiating the effects of a cytokine named interleukin (IL)-7 by securing its availability and bioactivity over time. This effect was mediated by an isoform of the IL-7 receptor that circulates at high levels in blood. IL-7 is an important factor for T-cell maturation and proliferation, and, hence, its association to MS, which is an autoimmune disease, is not surprising.
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| 30. |
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| 31. |
- Rajula, H. S. R., et al.
(författare)
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Overview of CAPICE-Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe-an EU Marie Sklodowska-Curie International Training Network
- 2022
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Ingår i: European Child & Adolescent Psychiatry. - : Springer Science and Business Media LLC. - 1018-8827 .- 1435-165X. ; 31:5, s. 829-839
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Tidskriftsartikel (refereegranskat)abstract
- The Roadmap for Mental Health and Wellbeing Research in Europe (ROAMER) identified child and adolescent mental illness as a priority area for research. CAPICE (Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe) is a European Union (EU) funded training network aimed at investigating the causes of individual differences in common childhood and adolescent psychopathology, especially depression, anxiety, and attention deficit hyperactivity disorder. CAPICE brings together eight birth and childhood cohorts as well as other cohorts from the EArly Genetics and Life course Epidemiology (EAGLE) consortium, including twin cohorts, with unique longitudinal data on environmental exposures and mental health problems, and genetic data on participants. Here we describe the objectives, summarize the methodological approaches and initial results, and present the dissemination strategy of the CAPICE network. Besides identifying genetic and epigenetic variants associated with these phenotypes, analyses have been performed to shed light on the role of genetic factors and the interplay with the environment in influencing the persistence of symptoms across the lifespan. Data harmonization and building an advanced data catalogue are also part of the work plan. Findings will be disseminated to non-academic parties, in close collaboration with the Global Alliance of Mental Illness Advocacy Networks-Europe (GAMIAN-Europe).
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| 33. |
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| 34. |
- van der Sluijs, AV, et al.
(författare)
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Assisted peritoneal dialysis across Europe: Practice variation and factors associated with availability
- 2021
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Ingår i: Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. - : SAGE Publications. - 1718-4304 .- 0896-8608. ; 41:6, s. 533-541
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Tidskriftsartikel (refereegranskat)abstract
- In Europe, the number of elderly end-stage kidney disease patients is increasing. Few of those patients receive peritoneal dialysis (PD), as many cannot perform PD autonomously. Assisted PD programmes are available in most European countries, but the percentage of patients receiving assisted PD varies considerably. Hence, we assessed which factors are associated with the availability of an assisted PD programme at a centre level and whether the availability of this programme is associated with proportion of home dialysis patients. Methods: An online survey was sent to healthcare professionals of European nephrology units. After selecting one respondent per centre, the associations were explored by χ 2 tests and (ordinal) logistic regression. Results: In total, 609 respondents completed the survey. Subsequently, 288 respondents from individual centres were identified; 58% worked in a centre with an assisted PD programme. Factors associated with availability of an assisted PD programme were Western European and Scandinavian countries (OR: 5.73; 95% CI: 3.07–10.68), non-academic centres (OR: 2.01; 95% CI: 1.09–3.72) and centres with a dedicated team for education (OR: 2.87; 95% CI: 1.35–6.11). Most Eastern & Central European respondents reported that the proportion of incident and prevalent home dialysis patients was <10% (72% and 63%), while 27% of Scandinavian respondents reported a proportion of >30% for both incident and prevalent home dialysis patients. Availability of an assisted PD programme was associated with a higher incidence (cumulative OR: 1.91; 95% CI: 1.21–3.01) and prevalence (cumulative OR: 2.81; 95% CI: 1.76–4.47) of patients on home dialysis. Conclusions: Assisted PD was more commonly offered among non-academic centres with a dedicated team for education across Europe, especially among Western European and Scandinavian countries where higher incidence and prevalence of home dialysis patients was reported.
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| 36. |
- Vestin, Jenny L. K., et al.
(författare)
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The influence of alkaline and non-alkaline parent material on Norway spruce tree chemical composition and growth rate
- 2013
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Ingår i: Plant and Soil. - : Springer Science and Business Media LLC. - 0032-079X .- 1573-5036. ; 370:1-2, s. 103-113
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated the influence of contrasting parent materials on tree chemical composition and growth rate under field conditions. On the island of Alno, Sweden, alkaline intrusions are interspersed into non-alkaline gneiss bedrock, which provides a unique opportunity to conduct this study with a minimum of confounding effects. Three plots with alkaline and three plots with non-alkaline parent material were established in a homogenous Norway spruce stand. The chemical composition of soil and soil solution was determined throughout the soil profiles. The chemical composition of bark, wood and needles was determined for each plot, and the latest 5 year basal area growth increment calculated. Concentrations of Ca in needles were correlated with the soil exchangeable Ca levels. Tree growth rate was significantly higher on the alkaline plots and positively correlated with soil concentrations of Ca, Mg, P, and Zn. The tree growth rate also tended to correlate with soil N concentrations, but levelled out for the highest soil N concentrations. Tree growth was enhanced on the alkaline plots and was correlated with several elements. However, none of these elements could be confirmed as the limiting one for tree growth at the current site.
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| 37. |
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| 38. |
- Zhou, D, et al.
(författare)
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Low copy numbers of complement C4 and C4A deficiency are risk factors for myositis, its subgroups and autoantibodies
- 2023
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 82:2, s. 235-245
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Tidskriftsartikel (refereegranskat)abstract
- Idiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases characterised by myositis-related autoantibodies plus infiltration of leucocytes into muscles and/or the skin, leading to the destruction of blood vessels and muscle fibres, chronic weakness and fatigue. While complement-mediated destruction of capillary endothelia is implicated in paediatric and adult dermatomyositis, the complex diversity of complementC4in IIM pathology was unknown.MethodsWe elucidated the gene copy number (GCN) variations of totalC4,C4AandC4B, longandshort genesin 1644 Caucasian patients with IIM, plus 3526 matched healthy controls using real-time PCR or Southern blot analyses. Plasma complement levels were determined by single radial immunodiffusion.ResultsThe large study populations helped establish the distribution patterns of variousC4GCN groups. Low GCNs ofC4T(C4T=2+3) andC4Adeficiency (C4A=0+1) were strongly correlated with increased risk of IIM with OR equalled to 2.58 (2.28–2.91), p=5.0×10−53forC4T, and 2.82 (2.48–3.21), p=7.0×10−57forC4Adeficiency. Contingency and regression analyses showed that among patients withC4Adeficiency, the presence ofHLA-DR3became insignificant as a risk factor in IIM except for inclusion body myositis (IBM), by which 98.2% hadHLA-DR3with an OR of 11.02 (1.44–84.4). Intragroup analyses of patients with IIM for C4 protein levels and IIM-related autoantibodies showed that those with anti-Jo-1 or with anti-PM/Scl had significantly lower C4 plasma concentrations than those without these autoantibodies.ConclusionsC4Adeficiency is relevant in dermatomyositis,HLA-DRB1*03is important in IBM and bothC4Adeficiency andHLA-DRB1*03contribute interactively to risk of polymyositis.
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