| 1. |
- Furmark, Tomas, et al.
(författare)
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Guided and unguided self-help for social anxiety disorder : randomised controlled trial
- 2009
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Ingår i: British Journal of Psychiatry. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 195:5, s. 440-447
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Tidskriftsartikel (refereegranskat)abstract
- Background Internet-delivered self-help programmes with added guidance have shown efficacy in social anxiety disorder, unguided self-help has been insufficiently studied. Aims To evaluate the efficacy of guided and unguided self-help social anxiety disorder. Method Participants followed a cognitive-behavioural self-help programme in the form of either pure bibliotherapy or an internet-based treatment with therapist guidance and online group discussions. A subsequent trial was conducted to evaluate treatment specificity. Participants (n=235) were randomised to one of three conditions in the first trial, or one of four conditions in the second. Results Pure bibliotherapy and the internet-based treatment were better than waiting list on measures of social anxiety, general anxiety, depression and quality of life. The internet-based therapy had the highest effect sizes, but directly comparable effects were noted for bibliotherapy augmented with online group discussions. Gains were well maintained a year later. Conclusions Unguided self-help through bibliotherapy can produce enduring improvement for individuals with social anxiety disorder.
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| 2. |
- Tillfors, Maria, 1963-, et al.
(författare)
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Treating university students with social phobia and public speaking fears : Internet delivered self-help with or without live group exposure sessions
- 2008
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Ingår i: Depression and anxiety (Print). - : Hindawi Limited. - 1091-4269 .- 1520-6394. ; 25:8, s. 708-717
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: This study investigated the efficacy of an Internet-based self-help program with minimal therapist contact via e-mail for Swedish university students with social phobia and public speaking fears. The main objective was to test if the Internet-based self-help program would be more effective if five live group exposure sessions were added. METHODS: Thirty-eight students meeting the diagnostic and statistical manual of mental disorders, 4th edition criteria for social phobia were randomized into two different treatment groups: Internet delivered cognitive behavior therapy combined with five group exposure sessions (ICBT+ exp) or the Internet program alone (ICBT). RESULTS: Results were analyzed on an intention-to-treat basis. Both treatment groups showed significant improvement from pre- to post-test, and from pre-test to 1-year follow-up, on all measured dimensions (social anxiety, general anxiety, depression levels, and quality of life). For both the groups, the average within-group effect sizes for the primary social anxiety scales, expressed as Cohen's d, were comparable to those seen in traditionally administered cognitive behavioral therapy both at post-test and at 1- year follow-up. CONCLUSIONS: The results suggest that the Internet-based self-help program on its own is efficient in the treatment of university students with social phobia. Adding group exposure sessions did not improve the outcome significantly.
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| 3. |
- Torén, Kjell, 1952, et al.
(författare)
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The ratio FEV1/FVC and its association to respiratory symptoms-A Swedish general population study
- 2021
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Ingår i: Clinical Physiology and Functional Imaging. - : Wiley. - 1475-0961 .- 1475-097X. ; 41:2, s. 181-191
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Tidskriftsartikel (refereegranskat)abstract
- Chronic airflow limitation (CAL) can be defined as fixed ratio of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) any respiratory symptom. In a cross-sectional general population study, 15,128 adults (50-64 years of age), 7,120 never-smokers and 8,008 ever-smokers completed a respiratory questionnaire and performed FEV1 and FVC after bronchodilation. We calculated different ratios of FEV1/FVC from 0.40 to 1.0 using 0.70 as reference category. We analysed odds ratios (OR) between different ratios and any respiratory symptom using adjusted multivariable logistic regression. Among all subjects, regardless of smoking habits, the lowest odds for any respiratory symptom was at FEV1/FVC = 0.82, OR 0.48 (95% CI 0.41-0.56). Among never-smokers, the lowest odds for any respiratory symptom was at FEV1/FVC = 0.81, OR 0.53 (95% CI 0.41-0.70). Among ever-smokers, the odds for any respiratory symptom was lowest at FEV1/FVC = 0.81, OR 0.43 (95% CI 0.16-1.19), although the rate of inclining in odds was small in the upper part, that is FEV1/FVC = 0.85 showed similar odds, OR 0.45 (95% CI 0.38-0.55). We concluded that the odds for any respiratory symptoms continuously decreased with higher FEV1/FVC ratios and reached a minimum around 0.80-0.85, with similar results among never-smokers. These results indicate that the optimal threshold associated with respiratory symptoms may be higher than 0.70 and this should be further investigated in prospective longitudinal studies.
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| 4. |
- Almevik, Gunnar, 1969, et al.
(författare)
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Crafting film instructions: e-learning in craft education
- 2019
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Ingår i: Make and learn, Nordic Research Conference in Sloyd, September 17-20, 2019, Gothenburg.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Academisation concerns the phenomenon where vocational and practice-oriented fields enter higher education, but also the fact that higher education in general becomes more firmly directed towards scholar competences and research. The ongoing academisation have put pressure on craft educations to develop more efficient pedagogical approaches to hands on skills-acquisition. This paper elaborate on combinations of film instruction and face-to-face learning to augment both hands-on skills and analytical attitudes in crafts. The paper reviews the research field and reflects on own experiences in the use of e-learning and filmed instructions in craft education. The research material consist of own production of film instructions and assessment of pedagogical uses in craft education in graduate courses. The research question is how e-learning can be used in craft education to complement and gear up the efficiency of face-to-face instruction? The preliminary result points at the need to develop a variety of genres of instructions. Filmed instructions need to be declared in terms of learning outcomes and constructively linked to other pedagogical formats of a course curriculum.
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| 5. |
- Arkkukangas, Marina, et al.
(författare)
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Older persons' experiences of a home-based exercise program with behavioral change support
- 2017
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Ingår i: Physiotherapy Theory and Practice. - : Taylor & Francis. - 0959-3985 .- 1532-5040. ; 33:12, s. 905-913
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is a challenge to promote exercise among older persons. Knowledge is needed regarding the maintenance of exercise aiming at preventing falls and promoting health and well-being in older persons.Purpose: This descriptive study used a qualitative inductive approach to describe older persons' experiences of a fall-preventive, home-based exercise program with support for behavioral change.Methods: Semi-structured interviews were conducted with 12 elderly persons aged 75years or older, and a qualitative content analysis was performed.Results: Four categories emerged: facilitators of performing exercise in everyday life, the importance of support, perceived gains from exercise, and the existential aspects of exercise.Conclusion: With support from physiotherapists (PTs), home-based exercise can be adapted to individual circumstances in a meaningful way. Including exercises in everyday life and daily routines could support the experience of being stronger, result in better physical functioning, and give hope for an extended active life in old age.
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| 6. |
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| 7. |
- Brorsson, Annelie, 1963, et al.
(författare)
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Development and evaluation of a new seated heel-rise test in the early stages of rehabilitation after an acute Achilles tendon rupture.
- 2014
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Ingår i: 16th ESSKA (European Society of Sports Traumatology, Knee Surgery and Arthroscopy) Congress, 14-17 May 2014, Amsterdam, Netherlands.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The early stages of rehabilitation appear to be of great importance for outcome after an Achilles tendon rupture. It is a challenge to evaluate the patients’ calf muscle endurance at this stage in a safe and adequate way. The aim of our study was to develop a seated heel-rise test suitable for evaluating calf muscle endurance three months after an Achilles tendon rupture. Furthermore we wanted to evaluate how the seated heel-rise test correlated to the ability to perform one-legged standing heel-rise and patient-reported symptoms. Method: Ninety-three patients, 79 men and 14 women, mean age of 40 (20-63) years, were included from a cohort of 100 patients participating in a prospective, randomized controlled trial comparing non-surgical and surgical treatment after Achilles tendon rupture. Forty-seven were treated with surgery and 46 with non-surgery. They were evaluated after 3, 6 and 12 months. Patient reported outcome was evaluated with Achilles Tendon Rupture Score (ATRS) and functional outcome with seated and standing heel-rise test. The seated heel-rise test was performed with the patient sitting with hip and knee in 90°. A leg extension weight-training machine was used to provide load onto the patient’s thigh at 50% body weight. The limb symmetry index (LSI=injured/healthy x 100) was calculated in order to compare the results from the seated and standing heel-rise test. Results: Ninety-one patients out of 93 (98%) could perform the seated heel-rise test. At the 3-month follow-up there was a significant difference (p<0.01) in the seated heel-rise test between the injured and the healthy side. There were no significant differences between the surgical and non-surgical treatment groups. There were significant differences in the seated heel-rise test and in ATRS (p<0.01) when comparing the group who could perform a standing heel-rise test at the 3-months follow-up, with the group who could not. There were significant correlations between the LSI-values in the seated heel-rise height at the 3-month follow-up and the standing heel-rise height at the 6-month (r=0.36, p<0.001, n= 91) and the 12-month follow-up (r=0.35, p=0.001, n=85). There were also significant correlations (r=0.22-0.37, p=<0.04) between the seated heel-rise test and ATRS. Conclusions: The seated heel-rise-test has the capacity to identify differences between the injured and the healthy side three months after injury. This test also correlates with patient reported outcomes and the heel-rise ability at 6 and 12 months. This test appears to be a safe and suitable test for evaluating calf muscle endurance and function in the early stages of rehabilitation after an Achilles tendon rupture.
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| 8. |
- Brorsson, Annelie, 1963, et al.
(författare)
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Long-term follow up after acute Achilles tendon rupture.
- 2015
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Ingår i: Danish Sports Medicine Congress, Copenhagen, January 22-24, 2015. - : Danish Association of Sports Medicine.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- It is still unknown why many patients never fully recover after an Achilles tendon rupture (ATR). The aim of this study was to perform a long-term follow-up (5-9 years) of patients treated either surgically or non-surgically after an ATR. Furthermore, we wanted to examine if the patients had a tendon elongation on the injured side and evaluate if this correlated to function, symptoms and foot structure. Material and Method Sixty-seven patients (13 women) mean age of 50 years were evaluated 5-9 years after injury. Thirty-five patients were treated with surgery and 32 with non-surgery. Patient reported outcome and activity level, lower leg function, tendon length, and foot-structure were evaluated. Both the healthy and the injured side were examined and the limb symmetry index (LSI=injured/healthy x 100) was calculated. Results There were significant differences between the healthy and injured side in all function tests (p<0.001-0.015) and the tendon was significantly longer on the injured side (p<0.001) independent of treatment. There were no significant correlations between tendon length and patient reported outcome, function or foot structure. The heel-rise height increased significantly (p<0.000) from the 1 year- to the 5-9-years-follow up. The mean Achilles tendon Total Rupture Score (ATRS) was 91/100, indicating minor symptoms. Conclusion: Patients with an Achilles tendon rupture continues to have significant deficits in tendon structure and function 5-9 years after injury. There is, however continued improvement between the 1 and 5-9 year follow-up.
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| 9. |
- Brorsson, Annelie, 1963, et al.
(författare)
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Recovery of calf muscle endurance 3 months after an Achilles tendon rupture.
- 2016
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Ingår i: Scandinavian journal of medicine & science in sports. - : Wiley. - 1600-0838 .- 0905-7188. ; 26:7, s. 844-853
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to evaluate calf muscle endurance in a seated position 3 months after an Achilles tendon rupture and to evaluate how the ability to perform standardized seated heel-rises correlated to the single-leg standing heel-rise test and to patient-reported symptoms evaluated with the Achilles tendon Total Rupture Score (ATRS) 3 and 6 months after the injury. Ninety-three patients were included from a cohort of 101 patients participating in a prospective, randomized controlled trial comparing surgical and nonsurgical treatment after Achilles tendon rupture. Forty-seven patients were treated surgically and 46 nonsurgically. Ninety-one patients out of 93 (98%) could perform the standardized seated heel-rises. At the 3-month follow-up, there was a significant difference (P<0.001) between the injured and the healthy side performing standardized seated heel-rises. There were also significant correlations (r=0.29-0.37, P=<0.05) between the standardized seated heel-rises and ATRS 3 and 6 months after injury in the group who could not perform single-leg standing heel-rises. There were no significant differences between the surgical and nonsurgical treatment groups. The evaluation of standardized seated heel-rises appears to be a useful tool to quantify progress and predict future functional performance and patient-reported symptoms.
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| 10. |
- Carlson, Annelie, 1969-, et al.
(författare)
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Energy use due to traffic and pavement maintenance : the cost effectiveness of reducing rolling resistance
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- There is a potential to reduce energy use of traffic by performing maintenance measures that lower the rolling resistance. However, the overall aim should be to decrease the total energy use in a life cycle perspective, including energy for both traffic and maintenance. When choosing maintenance alternative, it is also of importance to consider the costs involved. Pavement management is focused on keeping wide spread road networks in acceptable condition given certain budget constraints. Therefore, the economic constraints need to be addressed and in the case of choosing a maintenance alternative that reduces total energy, it also has to be cost-efficient in order for it to be performed. The main scope of the research presented in this report is to investigate how road management should act to reduce total energy use of roads, including traffic and maintenance induced energy use, while also taking cost efficiency and the aspect of uncertainty into consideration. The purpose is to enable a better consideration of the total energy used and maintenance cost when managing the road network. The objective is to derive a meaningful instrument for decision making situations such as when selecting and designing maintenance treatments, in which total energy use and maintenance cost is considered. A general method is developed and presented. A criterion, CR, has been identified for how to choose a pavement maintenance strategy in regards to cost and energy efficiency. A cost benefit analysis approach using Benefit to Cost Ratio, BCR, has been adopted. The study indicates that it is difficult to establish a simple rule of thumb. However, the CR-value may be a useful criterion in some circumstances and it is important to have guidelines as decision support where assessments are made of the road surface characteristics, total energy use and maintenance cost and where the different aspects are valued. This is especially important on an object level.
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| 11. |
- Carlson, Annelie, 1969-, et al.
(författare)
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Fordonsemissionsmodellen PHEM : förstudie om att inkludera vägytans betydelseför rullmotstånd och bränsleförbrukning
- 2021
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Rullmotståndet är en viktig komponent vid beräkning av bränsleförbrukning och emissioner. Denna rapport redovisar alternativ till metodutveckling för att med mikrosimuleringmodellen PHEM bättre kunna beakta vägytans påverkan på ett fordons rullmotstånd. Betydelsen av vägytans egenskaper har tidigare gjorts med modellen VETO där det går att ange specifika egenskaper hos vägen. Dessa möjligheter gör att VETO passar bra för analyser av hur vägens egenskaper påverkar bränsleförbruk-ningen. Samma möjligheter finns inte i PHEM. De utvecklingsalternativ som berörs i rapporten är att: (1) ändra källkoden till PHEM så att möjligheten att inkludera vägytans egenskaper blir samma som i VETO; (2) att i PHEM:s indatafiler lägga till en kolumn som ersätter rullmotståndet som beräknas av PHEM med ett rullmotstånd som beräknas på annat sätt och därmed kan koppla till vägytans egenskaper; (3) att ersätta rullmotståndsdelen i PHEM med motsvarande block i VETO med viss förenkling och (4) att sätta in ett referensfall från VETO i PHEM och göra övriga justeringar i efterhand med hjälp av VETO. Alternativen (1) till och med (3) ändrar rullmotståndsdelen men behåller allt övrigt inom PHEM medan (4) omfattar fler simuleringar. Alternativ (3) och (4) kräver inte någon ändring av källkoden.
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| 12. |
- Coignard, J, et al.
(författare)
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A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 1078-
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.
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| 13. |
- de-Wahl Granelli, Anne, 1970, et al.
(författare)
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Impact of pulse oximetry screening on the detection of duct dependent congenital heart disease: a Swedish prospective screening study in 39,821 newborns.
- 2009
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Ingår i: BMJ (Clinical research ed.). - 1468-5833. ; 338
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the use of pulse oximetry to screen for early detection of life threatening congenital heart disease. DESIGN: Prospective screening study with a new generation pulse oximeter before discharge from well baby nurseries in West Götaland. Cohort study comparing the detection rate of duct dependent circulation in West Götaland with that in other regions not using pulse oximetry screening. Deaths at home with undetected duct dependent circulation were included. SETTING: All 5 maternity units in West Götaland and the supraregional referral centre for neonatal cardiac surgery. PARTICIPANTS: 39,821 screened babies born between 1 July 2004 and 31 March 2007. Total duct dependent circulation cohorts: West Götaland n=60, other referring regions n=100. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive values, and likelihood ratio for pulse oximetry screening and for neonatal physical examination alone. RESULTS: In West Götaland 29 babies in well baby nurseries had duct dependent circulation undetected before neonatal discharge examination. In 13 cases, pulse oximetry showed oxygen saturations
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| 14. |
- Dork, T, et al.
(författare)
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Two truncating variants in FANCC and breast cancer risk
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 12524-
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Tidskriftsartikel (refereegranskat)abstract
- Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44–1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
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| 15. |
- Eriksson, Annelie, et al.
(författare)
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Distriktssköterskors beskrivningar av sjukdomsförebyggande arbete i daglig verksamhet och strukturella förutsättningar för detta arbete : [District nurses’ perceptions of their preventive work and structural conditions for this work]
- 2015
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Ingår i: Nordic journal of nursing research. - : Sage Publications. - 2057-1585 .- 2057-1593. ; 35:2, s. 77-84
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Tidskriftsartikel (refereegranskat)abstract
- Background There is much research about district nurses’ preventive work, effects of it and their perceptions of the preventive work. Less is known about how district nurses perceive their preventive work in relation to structural conditions for this work.Aim The aim was to describe district nurses’ perceptions of their preventive work in daily practice; and structural conditions for this using Kanter’s theory of structural empowerment.Methods Interviews were conducted 2012 with nine Swedish district nurses. Data were analysed using qualitative content analysis.Findings The analysis resulted in one theme; ‘To experience stimulation versus frustration; a consistency versus a discrepancy between will and structural conditions’. District nurses who worked with specialized tasks felt that they mostly had the structural conditions required to work in a preventive manner and that they could prioritize which unhealthy living habits to discuss with their patients. District nurses without specialized tasks described that their structural conditions for preventive work was limited in the present streamlined organization. This in turn led to a feeling of frustration.Conclusion Preventive work is described as stimulating when district nurses have the conditions required, yet the conditions required are sometimes lacking and especially for district nurses without specialized tasks. There is a will to work in a preventive manner but structural conditions need to be improved.
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| 16. |
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| 17. |
- Eriksson, Jessica, 1975-, et al.
(författare)
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Kreativ grammatikundervisning: från förskoleklass till åk 6
- 2017. - 2
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Huvudsyftet med Kreativ Grammatikundervisning är att både ge studenter på förskollärar- och lärarprogrammen (F-6) samt verksamma pedagoger nödvändiga ämneskunskaper och samtidigt visa hur man kan arbeta med grammatik på ett kreativt och inspirerande sätt.
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| 18. |
- Eriksson, Olle, 1967-, et al.
(författare)
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Förenklad bränsleförbrukningsfunktion : fokus på vägytans betydelse
- 2021
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Bränsleförbrukningen hos ett vägfordon påverkas av ett flertal faktorer. För att enklare och snabbare kunna göra analyser av bränsleförbrukningen, utan att göra faktiska mätningar i fordonen, är det önskvärt att kunna beskriva bränsleförbrukningens samband med dessa faktorer genom en funktion eller en modell. Det finns bränsleförbrukningsmodeller, men de kan vara byggda runt komplicerade sambandsfunktioner som är svåra att använda. De är oftast inte uttryckta som en summa av olika komponenter och erbjuder ingen möjlighet att enkelt diskutera komponenterna var och en för sig. Man kan t.ex. inte bryta ut en separat delmodell för att beräkna vad en åtgärd av vägytan får för effekt på bränsleförbrukningen. Det finns även bränsleförbrukningsfunktioner som är nära att uppträda som en summa av komponenter. Rapporten avser att använda en sådan funktion som utgångspunkt och förenkla något för att göra den till en summa av komponenter. Förenklingen utvärderas genom att sätta olika mått på hur mycket sämre resultat den förenklade funktionen ger, men samtidigt visa hur mycket mer användbar den blir. Det förekommer direkta effekter som att ojämnheter påverkar bränsleförbrukningen och indirekta som att ojämnheter påverkar hastigheten som påverkar luftmotståndet och bränsleförbrukningen. De direkta effekterna har störst utrymme i rapporten men de indirekta behandlas också utan att vara huvudföremål för rapporten. Modellerna är approximationer. Man kan behöva väga användbarhet och noggrannhet mot varandra och välja att använda en modell med enklare användning men sämre noggrannhet. För den valda modellen visar sig förenklingen av bränsleförbrukningsfunktionen fungera väl för personbil och lastbil men bara en del av förenklingen rekommenderas för lastbil med släp. Rapporten redovisar den förenklade funktionen och jämför med den ursprungliga. Den ger också exempel på beräkning av om en åtgärd kan motiveras ur energisynvinkel med den förenklade funktionen och jämför resultaten med och utan förenkling.
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| 19. |
- Eriksson Ström, Jonas, et al.
(författare)
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Airway regulatory T cells are decreased in COPD with a rapid decline in lung function
- 2020
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Ingår i: Respiratory Research. - : BioMed Central. - 1465-9921 .- 1465-993X. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Differences in the expression of regulatory T cells (Tregs) have been suggested to explain why some smokers develop COPD and some do not. Upregulation of Tregs in response to smoking would restrain airway inflammation and thus the development of COPD; while the absense of such upregulation would over time lead to chronic inflammation and COPD. We hypothesized that—among COPD patients—the same mechanism would affect rate of decline in lung function; specifically, that a decreased expression of Tregs would be associated with a more rapid decline in FEV1.Methods: Bronchoscopy with BAL was performed in 52 subjects recruited from the longitudinal OLIN COPD study; 12 with COPD and a rapid decline in lung function (loss of FEV1 ≥ 60 ml/year), 10 with COPD and a non-rapid decline in lung function (loss of FEV1 ≤ 30 ml/year), 15 current and ex-smokers and 15 non-smokers with normal lung function. BAL lymphocyte subsets were determined using flow cytometry.Results: The proportions of Tregs with regulatory function (FoxP3+/CD4+CD25bright) were significantly lower in COPD subjects with a rapid decline in lung function compared to those with a non-rapid decline (p = 0.019). This result was confirmed in a mixed model regression analysis in which adjustments for inhaled corticosteroid usage, smoking, sex and age were evaluated. No significant difference was found between COPD subjects and smokers or non-smokers with normal lung function.Conclusions: COPD subjects with a rapid decline in lung function had lower proportions of T cells with regulatory function in BAL fluid, suggesting that an inability to suppress the inflammatory response following smoking might lead to a more rapid decline in FEV1.
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| 20. |
- Eriksson Ström, Jonas, et al.
(författare)
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Chronic obstructive pulmonary disease is associated with epigenome-wide differential methylation in BAL lung cells
- 2022
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Ingår i: American Journal of Respiratory Cell and Molecular Biology. - : American Thoracic Society. - 1044-1549 .- 1535-4989. ; 66:6, s. 638-647
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Tidskriftsartikel (refereegranskat)abstract
- DNA methylation patterns in chronic pulmonary obstructive disease (COPD) might offer new insights into disease pathogenesis. To assess methylation profiles in the main COPD target organ, we performed an epigenome-wide association study on BAL cells. Bronchoscopies were performed in 18 subjects with COPD and 15 control subjects (ex- and current smokers). DNA methylation was measured using the Illumina MethylationEPIC BeadChip Kit, covering more than 850,000 CpGs. Differentially methylated positions (DMPs) were examined for 1) enrichment in pathways and functional gene relationships using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology, 2) accelerated aging using Horvath's epigenetic clock, 3) correlation with gene expression, and 4) colocalization with genetic variation. We found 1,155 Bonferroni-significant (P < 6.74 × 10-8) DMPs associated with COPD, many with large effect sizes. Functional analysis identified biologically plausible pathways and gene relationships, including enrichment for transcription factor activity. Strong correlation was found between DNA methylation and chronological age but not between COPD and accelerated aging. For 79 unique DMPs, DNA methylation correlated significantly with gene expression in BAL cells. Thirty-nine percent of DMPs were colocalized with COPD-associated SNPs. To the best of our knowledge, this is the first epigenome-wide association study of COPD on BAL cells, and our analyses revealed many differential methylation sites. Integration with mRNA data showed a strong functional readout for relevant genes, identifying sites where DNA methylation might directly affect expression. Almost half of DMPs were colocated with SNPs identified in previous genome-wide association studies of COPD, suggesting joint genetic and epigenetic pathways related to disease.
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| 21. |
- Eriksson Ström, Jonas, et al.
(författare)
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Cytotoxic lymphocytes in COPD airways : increased NK cells associated with disease, iNKT and NKT-like cells with current smoking
- 2018
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Ingår i: Respiratory Research. - : BMC. - 1465-9921 .- 1465-993X. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cytotoxic lymphocytes are increased in the airways of COPD patients. Whether this increase is driven primarily by the disease or by smoking is not clear, nor whether it correlates with the rate of decline in lung function.Methods: Bronchoscopy with BAL was performed in 52 subjects recruited from the longitudinal OLIN COPD study according to pre-determined criteria; 12 with COPD and a rapid decline in lung function (loss of FEV1 ≥ 60 ml/year), 10 with COPD and a non-rapid decline in lung function (loss of FEV1 ≤ 30 ml/year), 15 current and ex-smokers and 15 non-smokers with normal lung function. BAL lymphocyte subsets were determined using flow cytometry.Results: In BAL fluid, the proportions of NK, iNKT and NKT-like cells all increased with pack-years. Within the COPD group, NK cells – but not iNKT or NKT-like cells – were significantly elevated also in subjects that had quit smoking. In contrast, current smoking was associated with a marked increase in iNKT and NKT-like cells but not in NK cells. Rate of lung function decline did not significantly affect any of the results.Conclusions: In summary, increased proportions of NK cells in BAL fluid were associated with COPD; iNKT and NKT-like cells with current smoking but not with COPD. Interestingly, NK cell percentages did not normalize in COPD subjects that had quit smoking, indicating that these cells might play a role in the continued disease progression seen in COPD even after smoking cessation.Trial registration: Clinicaltrials.gov identifier NCT02729220.
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| 22. |
- Eriksson Ström, Jonas
(författare)
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Epigenetic changes and immunological features of chronic obstructive pulmonary disease
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Chronic obstructive pulmonary disease (COPD) is a heterogenous and chronic inflammatory syndrome with the lungs as its main target organ. Clinically, COPD is characterized by airflow limitation, chronic respiratory symptoms, and many extrapulmonary comorbidities. Tobacco smoke is the main environmental risk factor, but pollutants and smoke from biomass fuel are also major contributors. Why some, but not all, smokers develop the disease is a key but largely unresolved research question. Genetic factors seem to explain 40—60% of COPD susceptibility, but what additional role epigenetic factors such as DNA methylation might play has not been thoroughly investigated.Immune cells are of vital importance in the COPD pathogenesis. Among airway lymphocytes, cytotoxic CD8+ T cells are the ones most often found to be involved in the disease, but other lymphocyte populations are not as well studied.Among patients with manifest COPD, the rate of decline in lung function differs widely. Smoking cessation decreases the rate, but beyond that, it is not well understood why some patients experience a more rapid and some a much slower disease progression. Rapid decline is associated with a poor prognosis and has been recognized as a separate phenotype of COPD. Aim: The overall aim of this thesis was to examine the immunologic and epigenetic features of COPD with a focus on the rapid decline phenotype, using flow cytometry and measurement of DNA methylation in cells from bronchoalveolar lavage (BAL) fluid together with clinical characteristics such as rate of decline in lung function, use of inhaled corticosteroids and smoking status. The studies included in this thesis were all part of the Respiratory and Cardiovascular Effects in COPD (“KOLIN”) study.Methods: The study population was the same for all studies in this thesis. Subjects were recruited from the Obstructive Lung Disease in Northern Sweden (OLIN) COPD study according to predetermined criteria. OLIN COPD also provided the longitudinal data needed for classification of rapid/non-rapid decliners (decline in forced expiratory volume in the first second [FEV1] ≥60 or ≤30 mL/year respectively). BAL fluid was analyzed for cell type composition using flow cytometry. DNA methylation in BAL cells was measured using the Illumina MethylationEPIC BeadChip. In the statistical analysis, flow cytometry data was analyzed using group-wise comparisons and multivariable regression models. DNA methylation data was analyzed for association with COPD and accelerated epigenetic aging (defined as the difference between chronological and epigenetic age) using multilinear regression models. Differentially methylated positions and regions associated with COPD were analyzed for gene association and pathway enrichment and integrated with data from previous gene expression and genome-wide association studies.Results: Paper I: in this first paper based on flow cytometry, we focused on cytotoxic lymphocytes and found that Natural Killer (NK) cells in BAL were increased in COPD while invariant Natural Killer T (iNKT) and Natural Killer T-like (NKT-like) cells increased with smoking but not with COPD. NK cells were also higher when comparing ex-smokers with and without COPD. No significant differences were found between COPD subjects with a rapid vs. a non-rapid decline in lung function.Paper II: regulatory immune cells were investigated in this second flow cytometry-based paper. We found that FoxP3+ regulatory T cells (Tregs) were significantly lower in COPD subjects with a rapid decline in lung function compared to those with a non-rapid decline. This result was significant before as well as after adjustments for inhaled corticosteroids (ICS) usage and smoking. None of the investigated regulatory immune cell populations (T helper cells, activated T helper cells, and FoxP3+ Tregs) displayed significant differences associated with either COPD or smoking.Paper III: measurements of BAL cell DNA methylation revealed epigenome-wide differential methylation in COPD; 1,155 differentially methylated positions (DMPs) and 7,097 differentially methylated regions. Functional analysis using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology databases identified biologically plausible pathways and gene relationships, including enrichment for transcription factor activity. No correlation was found between COPD and accelerated aging. For 79 unique DMPs, DNA methylation correlated significantly with gene expression in BAL. Thirty-nine percent of DMPs were co-located with single nucleotide polymorphisms (SNPs) associated with COPD.Conclusions: Among cytotoxic cell types, the NK cell population stood out as it 1) was increased in COPD; and 2) did not normalize in COPD subjects that had quit smoking. This indicates that NK cells might contribute to the continued disease progression in COPD even after smoking cessation.COPD subjects with a rapid decline in lung function had significantly lower levels of Fox P3+ Tregs in BAL. Further longitudinal research is needed to establish the causal direction of this relationship, but based on the evidence available to date, I deem it more plausible that a low expression of Fox P3+ Tregs would lead to a rapid decline in lung function, than the other way around.Our epigenome-wide association study (EWAS) identified widespread differential methylation in COPD, and many DMPs displayed a strong correlation with gene expression. Somewhat less than half of DMPs were located in close proximity to COPD-associated SNPs, suggesting that these might be sites where genetic factors regulate methylation status. In sum, our findings suggest strong associations between epigenetic factors and COPD. As this was the first ever published EWAS of COPD based on BAL cells, results must be validated in future studies.
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| 23. |
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| 24. |
- Falkevall, Annelie, et al.
(författare)
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Reducing VEGF-B Signaling Ameliorates Renal Lipotoxicity and Protects against Diabetic Kidney Disease
- 2017
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 25:3, s. 713-726
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Tidskriftsartikel (refereegranskat)abstract
- Diabetic kidney disease (DKD) is the most common cause of severe renal disease, and few treatment options are available today that prevent the progressive loss of renal function. DKD is characterized by altered glomerular filtration and proteinuria. A common observation in DKD is the presence of renal steatosis, but the mechanism(s) underlying this observation and to what extent they contribute to disease progression are unknown. Vascular endothelial growth factor B (VEGF-B) controls muscle lipid accumulation through regulation of endothelial fatty acid transport. Here, we demonstrate in experimental mouse models of DKD that renal VEGF-B expression correlates with the severity of disease. Inhibiting VEGF-B signaling in DKD mouse models reduces renal lipotoxicity, re-sensitizes podocytes to insulin signaling, inhibits the development of DKD-associated pathologies, and prevents renal dysfunction. Further, we show that elevated VEGF-B levels are found in patients with DKD, suggesting that VEGF-B antagonism represents a novel approach to treat DKD.
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| 25. |
- Grävare Silbernagel, Karin, 1965, et al.
(författare)
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Sex Differences in Outcome After an Acute Achilles Tendon Rupture.
- 2015
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Ingår i: Orthopaedic journal of sports medicine. - : SAGE Publications. - 2325-9671. ; 3:6
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Tidskriftsartikel (refereegranskat)abstract
- Tendon healing differs between the sexes. Comparisons in outcome between the sexes after an Achilles tendon rupture are often not possible because of the small cohort (<20%) of women.
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