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1.
  • Beecham, Ashley H, et al. (författare)
  • Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
  • 2013
  • Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
  • Tidskriftsartikel (refereegranskat)abstract
    • Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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  • Jensen, A S, et al. (författare)
  • Prevalence of cerebral and pulmonary thrombosis in patients with cyanotic congenital heart disease.
  • 2015
  • Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 101:19, s. 1540-1546
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients with cyanotic congenital heart disease (CCHD) have a high prevalence of thrombosis, the most frequently described locations being the cerebral and pulmonary vessels. The reported prevalence of both cerebral infarction and pulmonary thrombosis has been highly variable. The aim of this study was to examine the prevalence of both cerebral and pulmonary thrombosis in CCHD according to medical history and imaging. In addition, the role of known erythrocytosis and haemostatic abnormalities as risk factors was evaluated.
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  • Stahl, Günter K., et al. (författare)
  • Sociocultural integration in mergers and acquisitions: Unresolved paradoxes and directions for future research
  • 2013
  • Ingår i: Thunderbird International Business Review. - : Wiley. - 1096-4762 .- 1520-6874. ; 55:4, s. 333-356
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite decades of research, the key factors for success in mergers and acquisitions (M&As) and the reasons why M&As often fail remain poorly understood. While attempts to explain M&A success and failure have traditionally focused on strategic and financial factors, an emergent field of inquiry has been directed at the sociocultural and human resources issues involved in the integration of acquired or merging firms. This research has sought to explain M&A performance and underperformance in terms of the impact that variables such as cultural fit, management style similarity, the pattern of dominance between merging firms, the acquirer's degree of cultural tolerance, and the social climate surrounding a takeover have on the postmerger integration process. In this article, we attempt to take stock of, and synthesize, the findings from research on sociocultural and human resources integration in M&A, to identify conflicting perspectives and unresolved questions as well as several underresearched areas, and then use our analyses to propose an agenda for the next stage of research in this field. © 2013 Wiley Periodicals, Inc.
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  • Boushel, Robert, et al. (författare)
  • Maintained peak leg and pulmonary VO2 despite substantial reduction in muscle mitochondrial capacity.
  • 2015
  • Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : Wiley. - 0905-7188 .- 1600-0838. ; 25:Suppl 4, s. 135-143
  • Tidskriftsartikel (refereegranskat)abstract
    • We recently reported the circulatory and muscle oxidative capacities of the arm after prolonged low-intensity skiing in the arctic (Boushel et al., 2014). In the present study, leg VO2 was measured by the Fick method during leg cycling while muscle mitochondrial capacity was examined on a biopsy of the vastus lateralis in healthy volunteers (7 male, 2 female) before and after 42 days of skiing at 60% HR max. Peak pulmonary VO2 (3.52 ± 0.18 L.min(-1) pre vs 3.52 ± 0.19 post) and VO2 across the leg (2.8 ± 0.4L.min(-1) pre vs 3.0 ± 0.2 post) were unchanged after the ski journey. Peak leg O2 delivery (3.6 ± 0.2 L.min(-1) pre vs 3.8 ± 0.4 post), O2 extraction (82 ± 1% pre vs 83 ± 1 post), and muscle capillaries per mm(2) (576 ± 17 pre vs 612 ± 28 post) were also unchanged; however, leg muscle mitochondrial OXPHOS capacity was reduced (90 ± 3 pmol.sec(-1) .mg(-1) pre vs 70 ± 2 post, P < 0.05) as was citrate synthase activity (40 ± 3 μmol.min(-1) .g(-1) pre vs 34 ± 3 vs P < 0.05). These findings indicate that peak muscle VO2 can be sustained with a substantial reduction in mitochondrial OXPHOS capacity. This is achieved at a similar O2 delivery and a higher relative ADP-stimulated mitochondrial respiration at a higher mitochondrial p50. These findings support the concept that muscle mitochondrial respiration is submaximal at VO2max , and that mitochondrial volume can be downregulated by chronic energy demand.
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  • Cardinale, Daniele A., 1982-, et al. (författare)
  • Muscle mass and inspired oxygen influence oxygen extraction at maximal exercise : role of mitochondrial oxygen affinity.
  • 2019
  • Ingår i: Acta Physiologica. - : Wiley-Blackwell. - 1748-1708 .- 1748-1716. ; 225:1
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM:We examined the Fick components together with mitochondrial O2 affinity (p50mito ) in defining O2 extraction and O2 uptake during exercise with large and small muscle mass during normoxia (NORM) and hyperoxia (HYPER).METHODS:Seven individuals performed two incremental exercise tests to exhaustion on a bicycle ergometer (BIKE) and two on a one-legged knee extension ergometer (KE) in NORM or HYPER. Leg blood flow and VO2 were determined by thermodilution and the Fick method. Maximal ADP-stimulated mitochondrial respiration (OXPHOS) and p50mito were measured ex vivo in isolated mitochondria. Mitochondrial excess capacity in the leg was determined from OXPHOS in permeabilized fibers and muscle mass measured with magnetic resonance imaging in relation to peak leg O2 delivery.RESULTS:The ex vivo p50mito increased from 0.06±0.02 to 0.17±0.04 kPa with varying substrate supply and O2 flux rates from 9.84±2.91 to 16.34±4.07 pmol O2 ·s-1 ·μg-1 respectively. O2 extraction decreased from 83% in BIKE to 67% in KE as a function of a higher O2 delivery, and lower mitochondrial excess capacity. There was a significant relationship between O2 extraction and mitochondrial excess capacity and p50mito that was unrelated to blood flow and mean transit time.CONCLUSION:O2 extraction varies with mitochondrial respiration rate, p50mito and O2 delivery. Mitochondrial excess capacity maintains a low p50mito which enhances O2 diffusion from microvessels to mitochondria during exercise. This article is protected by copyright. All rights reserved.
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  • de Waard, Anne-Karien M., et al. (författare)
  • Barriers and facilitators to participation in a health check for cardiometabolic diseases in primary care : A systematic review
  • 2018
  • Ingår i: European Journal of Preventive Cardiology. - : SAGE PUBLICATIONS LTD. - 2047-4873 .- 2047-4881. ; 25:12, s. 1326-1340
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Health checks for cardiometabolic diseases could play a role in the identification of persons at high risk for disease. To improve the uptake of these health checks in primary care, we need to know what barriers and facilitators determine participation.Methods: We used an iterative search strategy consisting of three steps: (a) identification of key-articles; (b) systematic literature search in PubMed, Medline and Embase based on keywords; (c) screening of titles and abstracts and subsequently full-text screening. We summarised the results into four categories: characteristics, attitudes, practical reasons and healthcare provider-related factors.Results: Thirty-nine studies were included. Attitudes such as wanting to know of cardiometabolic disease risk, feeling responsible for, and concerns about one's own health were facilitators for participation. Younger age, smoking, low education and attitudes such as not wanting to be, or being, worried about the outcome, low perceived severity or susceptibility, and negative attitude towards health checks or prevention in general were barriers. Furthermore, practical issues such as information and the ease of access to appointments could influence participation.Conclusion: Barriers and facilitators to participation in health checks for cardiometabolic diseases were heterogeneous. Hence, it is not possible to develop a one size fits all' approach to maximise the uptake. For optimal implementation we suggest a multifactorial approach adapted to the national context with special attention to people who might be more difficult to reach. Increasing the uptake of health checks could contribute to identifying the people at risk to be able to start preventive interventions.
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  • Hebert, Anders, et al. (författare)
  • Hemodynamic causes of exercise intolerance in Fontan patients.
  • 2014
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 175:3, s. 478-483
  • Tidskriftsartikel (refereegranskat)abstract
    • Exercise intolerance is frequent among Fontan patients and an important determinant for quality of life. This study investigated the hemodynamic causes of impaired exercise capacity in Fontan patients with particular focus on the influence of stroke volume index (SVI) and heart rate (HR).
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  • Hughes, Carmel M, et al. (författare)
  • Provision of pharmaceutical care by community pharmacists : a comparison across Europe
  • 2010
  • Ingår i: Pharmacy World & Science. - : Springer Science and Business Media LLC. - 0928-1231 .- 1573-739X. ; 32:4, s. 472-487
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To investigate the provision of pharmaceutical care by community pharmacists across Europe and to examine the various factors that could affect its implementation. Methods A questionnaire-based survey of community pharmacies was conducted within 13 European countries. The questionnaire consisted of two sections. The first section focussed on demographic data and services provided in the pharmacy. The second section was a slightly adapted version of the Behavioral Pharmaceutical Care Scale (BPCS) which consists of three main dimensions (direct patient care activities, referral and consultation activities and instrumental activities). Results Response rates ranged from 10–71% between countries. The mean total score achieved by community pharmacists, expressed as a percentage of the total score achievable, ranged from 31.6 (Denmark) to 52.2% (Ireland). Even though different aspects of pharmaceutical care were implemented to different extents across Europe, it was noted that the lowest scores were consistently achieved in the direct patient care dimension (particularly those related to documentation, patient assessment and implementation of therapeutic objectives and monitoring plans) followed by performance evaluation and evaluation of patient satisfaction. Pharmacists who dispensed higher daily numbers of prescriptions in Ireland, Germany and Switzerland had significantly higher total BPCS scores. In addition, pharmacists in England and Ireland who were supported in their place of work by other pharmacists scored significantly higher on referral and consultation and had a higher overall provision of pharmaceutical care. Conclusion The present findings suggest that the provision of pharmaceutical care in community pharmacy is still limited within Europe. Pharmacists were routinely engaged in general activities such as patient record screening but were infrequently involved in patient centred professional activities such as the implementation of therapeutic objectives and monitoring plans, or in self-evaluation of performance.
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  • Johansson, M. S., et al. (författare)
  • Chronic opioid use before and after exercise therapy and patient education among patients with knee or hip osteoarthritis
  • 2022
  • Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 30:11, s. 1536-1544
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate changes in opioid use after supervised exercise therapy and patient education among knee or hip osteoarthritis patients with chronic opioid use. Method: In this cohort study, we linked data from the Good Life with osteoArthritis in Denmark register (GLA:D®; standardised treatment program for osteoarthritis; January 2013 to November 2018) with national health registries. Among 35,549 patients, 1,262 were classified as chronic opioid users based on amount and temporal distribution of dispensed opioids the year before the intervention. We investigated changes in opioid use, measured as mg oral morphine equivalents (OMEQs), from the year before the intervention to the year after using generalized estimating equations. Results: We found a 10% decrease in mg OMEQs from the year before to the year after the intervention (incidence rate ratio [IRR]: 0.90, 95% confidence interval [CI]: 0.86, 0.94). Additional analyses suggested this decrease to be mainly attributable to regulatory actions targeting opioid prescribing during the study period (IRR among patients participating in the intervention before: 0.98 [95% CI: 0.89, 1.07] vs after: 0.83 [0.74, 0.93] regulatory actions). In a random general population sample of matched chronic opioid users, a similar opioid use pattern was observed over time, further supporting the impact of regulatory actions on the opioid use in the study population. Conclusion: Among patients with knee or hip osteoarthritis and chronic opioid use, a standardised treatment program did not change opioid use when regulatory changes in opioid prescribing were taken into account.
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  • Kopic, S., et al. (författare)
  • Isolated pulmonary regurgitation causes decreased right ventricular longitudinal function and compensatory increased septal pumping in a porcine model
  • 2017
  • Ingår i: Acta Physiologica. - : Wiley. - 1748-1716 .- 1748-1708. ; 221:3, s. 163-173
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: Longitudinal ventricular contraction is a parameter of cardiac performance with predictive power. Right ventricular (RV) longitudinal function is impaired in patients with free pulmonary regurgitation (PR) following corrective surgery for Tetralogy of Fallot (TOF). It remains unclear whether this is a consequence of the surgical repair, or whether it is inherent to PR. The aim of this study was to assess the relationship between longitudinal, lateral and septal pumping in a porcine model of isolated PR. Methods: Piglets were divided into a control (n = 8) group and a treatment (n = 12) group, which received a stent in the pulmonary valve orifice, inducing PR. After 2-3 months, animals were subjected to cardiac magnetic resonance imaging. A subset of animals (n = 6) then underwent percutaneous pulmonary valve replacement (PPVR) with follow-up 1 month later. Longitudinal, lateral and septal contributions to stroke volume (SV) were quantified by measuring volumetric displacements from end-diastole to end-systole in the cardiac short axis and long axis. Results: PR resulted in a lower longitudinal contribution to RV stroke volume, compared to controls (60.0 ± 2.6% vs. 73.6 ± 3.8%; P = 0.012). Furthermore, a compensatory increase in septal contribution to RVSV was observed (11.0 ± 1.6% vs. -3.1 ± 1.5%; P < 0.0001). The left ventricle (LV) showed counter-regulation with an increased longitudinal LVSV. Changes in RV longitudinal function were reversed by PPVR. Conclusion: These findings suggest that PR contributes to decreased RV longitudinal function in the absence of scarring from cardiac surgery. Measurement of longitudinal RVSV may aid risk stratification and timing for interventional correction of PR in TOF patients.
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  • Rudstam, Gabriella, et al. (författare)
  • Trauma-focused group music and imagery with women suffering from PTSD/Complex PTSD : A randomized controlled study
  • 2022
  • Ingår i: European Journal of Trauma & Dissociation. - : Elsevier. - 2468-7499. ; 6:3
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundWomen with a history of physical, sexual, and/or emotional abuse often suffer from post-traumatic stress disorder (PTSD) or complex posttraumatic stress disorder (CPTSD). Meta-analyses report that cognitive behavioural therapies (CBTs), followed by eye movement desensitization and reprocessing (EMDR) are the most studied psychotherapies for trauma treatment. Focus primarily lies on individual therapy – even though some studies on group therapy for trauma treatment also exist. Few studies exist regarding other alternative therapy forms, such as art-based psychotherapies or body-focused therapies.AimThis study investigated effects from the group music and imagery (GrpMI) method – a type of receptive music therapy – on trauma-related symptoms in women suffering from PTSD or CPTSD after physical, psychological, and/or sexual abuse.Material and methodsUsing a randomized controlled parallel-group design, a sample of 45 women were either assigned to a treatment group (T) who received 12 weekly treatment sessions of GrpMI or to a waiting list control group (WLC). Self-report scales were administered immediately before and after the intervention and at a three-month follow-upResultsA two-way mixed ANOVA showed a large group-by-time interaction effect on PTSD symptom severity (F(1, 42) = 8.68, p = .005 and Cohen's d = 0.94). A repeated-measures ANOVA showed a large effect within the T group (F(1, 20) = 16.6, p = .001, dav = 1.02), and the improvement remained at follow-up. The drop-out rate in the T group was as low as 4.5%.ConclusionThe findings suggest that GrpMI may be efficacious for treating women with PTSD/CPTSD, but further controlled studies with larger samples are warranted. The study is registered at ClinicalTrials.gov (Registration number: NCT03503526)
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  • Stenström, P, et al. (författare)
  • Total colonic aganglionosis: multicentre study of surgical treatment and patient-reported outcomes up to adulthood.
  • 2020
  • Ingår i: BJS open. - 2474-9842. ; 4:5, s. 943-953
  • Tidskriftsartikel (refereegranskat)abstract
    • Surgery for total colonic aganglionosis (TCA) is designed to preserve continence and achieve satisfactory quality of life. This study evaluated a comprehensive group of clinical and social outcomes.An international multicentre study from eight Nordic hospitals involving examination of case records and a patient-reported questionnaire survey of all patients born with TCA between 1987 and 2006 was undertaken.Of a total of 116 patients, five (4·3 per cent) had died and 102 were traced. Over a median follow-up of 12 (range 0·3-33) years, bowel continuity was established in 75 (73·5 per cent) at a median age of 11 (0·5-156) months. Mucosectomy with a short muscular cuff and straight ileoanal anastomosis (SIAA) (29 patients) or with a J pouch (JIAA) (26) were the most common reconstructions (55 of 72, 76 per cent). Major early postoperative complications requiring surgical intervention were observed in four (6 per cent) of the 72 patients. In 57 children aged over 4 years, long-term functional bowel symptoms after reconstruction included difficulties in holding back defaecation in 22 (39 per cent), more than one faecal accident per week in nine (16 per cent), increased frequency of defaecation in 51 (89 per cent), and social restrictions due to bowel symptoms in 35 (61 per cent). Enterocolitis occurred in 35 (47 per cent) of 72 patients. Supplementary enteral and/or parenteral nutrition was required by 51 (55 per cent) of 93 patients at any time during follow-up. Of 56 responders aged 2-20 years, true low BMI for age was found in 20 (36 per cent) and 13 (23 per cent) were short for age.Reconstruction for TCA was associated with persistent bowel symptoms, and enterocolitis remained common. Multidisciplinary follow-up, including continuity of care in adulthood, might improve care standards in patients with TCA.
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  • Stenum, Thomas Søndergaard, et al. (författare)
  • RNA interactome capture in Escherichia coli globally identifies RNA-binding proteins
  • 2023
  • Ingår i: Nucleic Acids Research. - : Oxford University Press. - 0305-1048 .- 1362-4962. ; 51:9, s. 4572-4587
  • Tidskriftsartikel (refereegranskat)abstract
    • RNA-binding proteins (RPBs) are deeply involved in fundamental cellular processes in bacteria and are vital for their survival. Despite this, few studies have so far been dedicated to direct and global identification of bacterial RBPs. We have adapted the RNA interactome capture (RIC) technique, originally developed for eukaryotic systems, to globally identify RBPs in bacteria. RIC takes advantage of the base pairing potential of poly(A) tails to pull-down RNA-protein complexes. Overexpressing poly(A) polymerase I in Escherichia coli drastically increased transcriptome-wide RNA polyadenylation, enabling pull-down of crosslinked RNA-protein complexes using immobilized oligo(dT) as bait. With this approach, we identified 169 putative RBPs, roughly half of which are already annotated as RNA-binding. We experimentally verified the RNA-binding ability of a number of uncharacterized RBPs, including YhgF, which is exceptionally well conserved not only in bacteria, but also in archaea and eukaryotes. We identified YhgF RNA targets in vivo using CLIP-seq, verified specific binding in vitro, and reveal a putative role for YhgF in regulation of gene expression. Our findings present a simple and robust strategy for RBP identification in bacteria, provide a resource of new bacterial RBPs, and lay the foundation for further studies of the highly conserved RBP YhgF.
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  • Søndergaard, M. L. J., et al. (författare)
  • Feminist Voices about Ecological Issues in HCI
  • 2022
  • Ingår i: Conference on Human Factors in Computing Systems - Proceedings. - New York, NY, USA : Association for Computing Machinery (ACM).
  • Konferensbidrag (refereegranskat)abstract
    • Even though issues such as climate change, pollution, and declining biodiversity impact us all, people with historically disenfranchised and socio-politically marginalized (HDSM) identities often bear the harsher brunt of ecological crises and suffer disproportionately. There is a need for listening to the voices of people with intersecting HDSM identities in relation to feminist engagements with ecological issues as applicable to HCI and IxD research and practice. Building upon and braiding together two thriving HCI discourses on feminism and environmental sustainability, we invite submissions from researchers, designers, educators, and activists interested in the intersections of feminist and ecological issues with a priority towards the well-being of people with HDSM identities. Converging feminist concerns on power, voice, and public discourse through this online workshop distributed across three time-zones, we hope to provide a forum for contemporary feminist voices as agents of change while engaging with ecological issues through an intersectional feminist orientation.
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