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Sökning: WFRF:(Thor Maria)

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1.
  • Hudson, Lawrence N, et al. (författare)
  • The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
  • 2017
  • Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
  • Tidskriftsartikel (refereegranskat)abstract
    • The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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2.
  • Zamora, Juan Carlos, et al. (författare)
  • Considerations and consequences of allowing DNA sequence data as types of fungal taxa
  • 2018
  • Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
  • Tidskriftsartikel (refereegranskat)abstract
    • Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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3.
  • Martrat, Griselda, et al. (författare)
  • Exploring the link between MORF4L1 and risk of breast cancer
  • 2011
  • Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 13:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens. Methods: Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk. Results: A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to g-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, P-trend = 0.45 and 0.05, P-2df = 0.51 and 0.14, respectively; and rs10519219, P-trend = 0.92 and 0.72, P-2df = 0.76 and 0.07, respectively. Conclusions: While the present study expands on the role of MRG15 in the control of genomic stability, weak associations cannot be ruled out for potential low-penetrance variants at MORF4L1 and BrCa risk among BRCA2 mutation carriers.
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4.
  • Estrada, Karol, et al. (författare)
  • Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
  • 2012
  • Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
  • Tidskriftsartikel (refereegranskat)abstract
    • Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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5.
  • Abrahamsson, Cecilia, et al. (författare)
  • TMD before and after correction of dentofacial deformities by orthodontic and orthognathic treatment
  • 2013
  • Ingår i: International Journal of Oral and Maxillofacial Surgery. - : Elsevier. - 0901-5027 .- 1399-0020. ; 46:6, s. 752-758
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract The aims of the study were to investigate the alteration of temporomandibular disorders (TMD) after correction of dentofacial deformities by orthodontic treatment in conjunction with orthognathic surgery; and to compare the frequency of TMD in patients with dentofacial deformities with an age and gender matched control group. TMD were evaluated in 121 consecutive patients (treatment group), referred for orthognathic surgery, by a questionnaire and a clinical examination. 18 months after treatment, 81% of the patients completed a follow-up examination. The control group comprised 56 age and gender matched subjects, of whom 68% presented for follow-up examination. TMD were diagnosed according to research diagnostic criteria for TMD. At baseline examination, the treatment group had a higher frequency of myofascial pain (P=.035) and arthralgia (P=.040) than the control group. At follow-up, the frequencies of myofascial pain, arthralgia and disc displacement had decreased in the treatment group (P=.050, P=.004, P=.041, respectively). The frequency of TMD was comparable in the two groups at follow-up. Patients with dentofacial deformities, corrected by orthodontic treatment in conjunction with orthognathic surgery, seem to have a positive treatment outcome in respect of TMD pain
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6.
  • Abrahamsson, Cecilia, et al. (författare)
  • TMD in consecutive patients referred for orthognathic surgery
  • 2009
  • Ingår i: Angle orthodontist. - : The Angle Orthodontist (EH Angle Education & Research Foundation). - 0003-3219 .- 1945-7103. ; 33:4, s. 201-226
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To answer the question whether temporomandibular disorders (TMD) were more common in a group of individuals referred for orthognathic surgery than in a control group. The null hypothesis was that neither the frequency of signs and symptoms of TMD or diagnosed TMD would differ between the patient group and a control group. MATERIALS AND METHODS: A sample of 121 consecutive patients referred for orthognathic surgery at the Department of Oral Maxillofacial Surgery, Malmö University Hospital, Sweden, was interviewed and examined regarding signs and symptoms of TMD and headaches. A control group was formed by 56 age- and gender-matched individuals attending the Department of Oral Diagnosis, Faculty of Odontology, Malmö University, Sweden, and Public Dental Health Clinic in Oxie, County of Skane, Sweden. TMD diagnoses were used according to Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). RESULTS: The patient group showed more myofascial pain without limited opening, disc displacement with reduction, and arthralgia according to RDC/TMD than the control group. The patient group also had more symptoms and signs of TMD in general. CONCLUSIONS: The null hypothesis was rejected because patients who were to be treated with orthognathic surgery had more signs and symptoms of TMD and higher frequency of diagnosed TMD compared with the matched control group.
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7.
  • Aevarsson, Arnthór, et al. (författare)
  • Going to extremes - a metagenomic journey into the dark matter of life
  • 2021
  • Ingår i: FEMS Microbiology Letters. - : Oxford University Press (OUP). - 1574-6968. ; 368:12
  • Forskningsöversikt (refereegranskat)abstract
    • The Virus-X-Viral Metagenomics for Innovation Value-project was a scientific expedition to explore and exploit uncharted territory of genetic diversity in extreme natural environments such as geothermal hot springs and deep-sea ocean ecosystems. Specifically, the project was set to analyse and exploit viral metagenomes with the ultimate goal of developing new gene products with high innovation value for applications in biotechnology, pharmaceutical, medical, and the life science sectors. Viral gene pool analysis is also essential to obtain fundamental insight into ecosystem dynamics and to investigate how viruses influence the evolution of microbes and multicellular organisms. The Virus-X Consortium, established in 2016, included experts from eight European countries. The unique approach based on high throughput bioinformatics technologies combined with structural and functional studies resulted in the development of a biodiscovery pipeline of significant capacity and scale. The activities within the Virus-X consortium cover the entire range from bioprospecting and methods development in bioinformatics to protein production and characterisation, with the final goal of translating our results into new products for the bioeconomy. The significant impact the consortium made in all of these areas was possible due to the successful cooperation between expert teams that worked together to solve a complex scientific problem using state-of-the-art technologies as well as developing novel tools to explore the virosphere, widely considered as the last great frontier of life.
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8.
  • Ali, Sadiq Mohammad, et al. (författare)
  • Social capital, the miniaturisation of community, traditionalism and first time acute myocardial infarction: A prospective cohort study in southern Sweden.
  • 2006
  • Ingår i: Social Science and Medicine. - : Elsevier BV. - 1873-5347 .- 0277-9536. ; 63:8, s. 2204-2217
  • Tidskriftsartikel (refereegranskat)abstract
    • This longitudinal study investigates the impact of social participation, trust and the combinations of social participation and trust on the incidence of first time acute myocardial infarction (AMI) in the population of Scania, southern Sweden. It is based on the cross-sectional 2000 public-health survey in Scania with a 59% participation rate and 13,604 participants, and prospective morbidity/mortality data collected for three years (January 2000-December 2002). The study cohort was followed prospectively to examine first ever AMI Hazard rate ratios (HRR) for first time AMI in the social participation, trust and social participation/trust combinations were calculated in a Cox regression model with adjustments for age, sex, education, economic stress, daily smoking, leisure time physical activity, body mass index (BMI), and self-reported health. The prevalence of low social participation was 32.8% among men and 31.5% among women. The prevalence of low trust was 40.0% among men and 44.2% among women. The three-year first time AMI rate was significantly higher among people with higher age, low education, daily smoking, poor self-reported health (among men), low social participation, and the combinations of low social participation/high trust and low social participation/low trust. The results show that low social participation but not trust was significantly associated with first time AMI after adjustment for age and sex. The positive association between low social participation and myocardial infarction remained significant after further adjustments for education, economic stress, daily smoking, physical activity and BMI, and became not significant only after additional adjustment for self-reported health, HRR 1.3 (0.9-2.0). High trust in combination with low social participation as well as low social capital (low trust/low social participation) were significantly associated with AMI, but after multiple adjustments only the low social participation/high trust category remained significant, HRR 1.6 (1.0-2.6).
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9.
  • Andersen, Thomas, et al. (författare)
  • C-X-C Ligand 16 Is an Independent Predictor of Cardiovascular Death and Morbidity in Acute Coronary Syndromes
  • 2019
  • Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 39:11, s. 2402-2410
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective:The chemokine CXCL16 (C-X-C motif ligand 16) is a scavenger receptor for OxLDL (oxidized low-density lipoproteins) and involved in inflammation at sites of atherosclerosis. This study aimed to investigate the association of CXCL16 with clinical outcome in patients with acute coronary syndrome.Approach and Results:Serial measurements of CXCL16 were performed in a subgroup of 5142 patients randomized in the PLATO trial (Platelet Inhibition and Patient Outcome). Associations between CXCL16 and a composite of cardiovascular death, spontaneous myocardial infarction or stroke, and the individual components were assessed by multivariable Cox regression analyses. The hazard ratio per 50% increase in admission levels of CXCL16 analyzed as continuous variable was 1.64 (95% CI, 1.44-1.88), P<0.0001. This association remained statistically significant after adjustment for randomized treatment, clinical variables, CRP (C-reactive protein), leukocytes, cystatin C, NT-proBNP (N-terminal pro-brain natriuretic peptide), troponin T, GDF-15 (growth differentiation factor 15), and other biomarkers; hazard ratio 1.23 (1.05-1.45), P=0.0126. The admission level of CXCL16 was independently associated with cardiovascular death (1.50 [1.17-1.92], P=0.0014) but not with ischemic events alone, in fully adjusted analyses. No statistically independent association was found between CXCL16 measured at 1 month, or change in CXCL16 from admission to 1 month, and clinical outcomes.Conclusions:In patients with acute coronary syndrome, admission level of CXCL16 is independently related to adverse clinical outcomes, mainly driven by an association to cardiovascular death. Thus, CXCL16 measurement may enhance risk stratification in patients with this condition.
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10.
  • Artigas Soler, María, et al. (författare)
  • Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.
  • 2011
  • Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1082-90
  • Tidskriftsartikel (refereegranskat)abstract
    • Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.
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11.
  • Auffret, Alistair, et al. (författare)
  • Can field botany be effectively taught as a distance course? Experiences and reflections from the COVID-19 pandemic
  • 2022
  • Ingår i: AoB PLANTS. - : Oxford University Press (OUP). - 2041-2851. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • The COVID-19 pandemic that started in 2020 forced a rapid change in university teaching, with large numbers of courses switching to distance learning with very little time for preparation. Courses involving many practical elements and field excursions required particular care if students were to fulfil planned learning outcomes. Here, we present our experiences in teaching field botany in 2020 and 2021. Using a range of methods and tools to introduce students to the subject, promote self-learning and reflection and give rapid and regular feedback, we were able to produce a course that allowed students to achieve the intended learning outcomes and that obtained similarly positive student evaluations to previous years. The course and its outcomes were further improved in 2021. We describe how we structured field botany as a distance course in order that we could give the best possible learning experience for the students. Finally, we reflect on how digital tools can aid teaching such subjects in the future, in a world where public knowledge of natural history is declining.In an era of large-scale biodiversity change and reductions in basic knowledge of natural history, it is important that practical courses in subjects like field botany continue to be taught effectively. Forced by the COVID-19 pandemic to teach plant identification with no direct contact with students, we used a range of methods and tools to promote self-learning and reflection in students, and to facilitate rapid feedback by teachers. Here, we present our method for producing a course that allowed students to achieve the intended learning outcomes and that obtained positive student evaluations.
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12.
  • Baturova, Maria A., et al. (författare)
  • Atrial fibrillation as a clinical characteristic of arrhythmogenic right ventricular cardiomyopathy : Experience from the Nordic ARVC Registry
  • 2020
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 298, s. 39-43
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Recent studies in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients have drawn attention to atrial fibrillation (AF) as an arrhythmic manifestation of ARVC and as an indicator of atrial involvement in the disease progression. We aimed to assess the prevalence of AF in the Scandinavian cohort of ARVC patients and to evaluate its association with disease clinical manifestations. Methods: Study sample comprised of 293 definite ARVC patients by 2010 Task Force criteria (TFC2010) and 141 genotype-positive family members (total n = 434, 43% females, median age at ARVC diagnosis 41 years [interquartile range (IQR) 28–52 years]). ARVC diagnostic score was calculated as the sum of major (2 points) and minor (1 point) criteria in all categories of the TFC2010. Results: AF was diagnosed in 42 patients (10%): in 41 patients with definite ARVC diagnosis (14%) vs in one genotype-positive family member (1%), p < 0.001. The median age at AF onset was 51 (IQR 38–58) years. The prevalence of AF was related to the ARVC diagnostic score: it significantly increased starting with the diagnostic score 4 (2% in those with score 3 vs 13% in those with score 4, p = 0.023) and increased further with increased diagnostic score (Somer's d value is 0.074, p < 0.001). Conclusion: AF is seen in 14% of definite ARVC patients and is related to the severity of disease phenotype thus suggesting AF being an arrhythmic manifestation of this cardiomyopathy indicating atrial myocardial involvement in the disease progression.
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13.
  • Bergerum, Carolina, 1967-, et al. (författare)
  • How might patient involvement in healthcare quality improvement efforts work—A realist literature review
  • 2019
  • Ingår i: Health Expectations. - : Wiley. - 1369-6513 .- 1369-7625. ; 00:00, s. 1-13
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction This realist literature review, regarding active patient involvement in healthcare quality improvement (QI), seeks to identify possible mechanisms that contribute to success or failure. Furthermore, the paper outlines key considerations for organising and supporting patient involvement in healthcare QI efforts. Methods Two literature searches were performed. Altogether, 1,204 articles from a healthcare context were screened, focusing on improvement efforts that involve patients, healthcare professionals and/or managers and leaders. Among these, 107 articles fulfilled the chosen study selection criteria and were further analysed. 18 articles underwent a full realist review. In the realist synthesis, context-mechanism-outcome configurations were articulated as middle-range theories and organised thematically to generate a program theory on how active patient involvement in QI efforts might work. Results The articles exhibited a diversity of patient involvement approaches at different levels of healthcare organisations. To be successful, organisations’ support of QI efforts that actively involved patients tailored the QI efforts to their context to achieve the desired outcomes, and involved the relevant microsystem members. Furthermore, it promoted interaction and partnership within the microsystem, and supported the behavioural change that follows.Conclusion This realist synthesis generates a program theory for active patient involvement in QI efforts; active patient involvement can be a tool (resource), if tailored for interaction and partnership (reasoning), that leads to behaviour change (outcome) within healthcare QI efforts. The theory explains essential resource and reasoning mechanisms, and outcomes that together form guidance for healthcare organisations when managing active patient involvement in QI efforts.
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14.
  • Bergerum, Carolina, 1967-, et al. (författare)
  • Organising and managing patient and public involvement to enhance quality improvement—Comparing a Swedish and a Dutch hospital
  • 2022
  • Ingår i: Health Policy. - : Elsevier. - 0168-8510 .- 1872-6054. ; 126:7, s. 603-612
  • Tidskriftsartikel (refereegranskat)abstract
    • As co-production approaches to quality improvement (QI) gain importance in healthcare, hospital leaders and managers are expected to organise and support such efforts. Yet, patient and public involvement (PPI) can be challenging. Hospital organisations, emphasising knowledge and evidence domains, are characterised by operational-professional rather than patient-preference led management. Thus, PPI adds aspects of influence and responsibility that are not clearly defined or understood, with limited knowledge about how it can be orchestrated. This study, therefore, aimed to explore hospital leaders’ and managers’ contextualised experiences of managing QI efforts involving patients, by comparing two European hospitals.The study draws on field observations and qualitative interviews with a total of 21 QI team leaders and hospital managers in a Swedish and a Dutch hospital organisation. The data were subjected to thematic analysis with a critical realist approach.Results define seven themes, or areas, in which mechanisms are at play: (1) patient involvement in hospital QI, and (2) improving outcomes for patients, originating from the strategic view of achieving the hospital vision. Furthermore, (3) societal influence, (4) knowledge and evidence, (5) complexity, (6) individual resources, and (7) cooperation are areas in which mechanisms operate in the process. These areas are equally relevant for both hospitals, yet the mechanisms involved play out differently depending on contextual structure and local means of action.
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15.
  • Bergerum, Carolina, 1967- (författare)
  • Patient and public involvement in hospital quality improvement interventions : the mechanisms, monitoring and management
  • 2022
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This dissertation focuses on the mechanisms, monitoring and management of patient and public involvement in hospital quality improvement (QI) interventions. Findings from a literature review generated an initial programme theory (PT) on active patient involvement in healthcare QI interventions (Paper 1). Empirical studies were also undertaken in order to describe what was actually happening in the hospital QI teams and what patients and professionals experience influence their joint involvement (Paper 2), and to compare hospital leaders’ and managers’ experiences of managing QI interventions involving patients and the public (Paper 3). Finally, it was studied how patient-reported measures stimulate patient involvement in QI interventions in practice (Paper 4). The research had a qualitative design. The approach was descriptive and comparative, and the studies were carried out prospectively. Data were collected in two hospital organisations in Sweden and in one hospital organisation in the Netherlands. Data collection methods were a literature search (Paper 1), interviews and field observations (Paper 2 and 3) and data collection meetings (Paper 4). Altogether, 93 team meetings and meetings between the team leaders and management were attended and a total of 20 days of study visits with different forms of meetings were made. Twelve patients, 12 healthcare professionals and 17 and 8 hospital leaders and managers, respectively, participated in the interviews and data collection meetings. Realist synthesis was used to formulate the initial PT (Paper 1). Constructivist grounded theory was used to analyse and describe what was happening in the QI teams and how it was experienced by the team members (Paper 2). To compare hospital leaders’ and managers’ different, contextual meanings in Sweden and the Netherlands, the reflexive thematic analysis informed by critical realism was used (Paper 3). To order, manage and map data from 31 examples of local QI interventions associated to patient-reported measures, the framework method was used (Paper 4). The results formulate a generic PT on the mechanisms, monitoring and management perspectives of co-produced QI interventions in hospital services where patients and the public are involved. The PT provides a hypothesis on the various mechanisms at play and outcomes obtained at the different levels of hospital organisations in the process. It is argued that focus should be on experiences, interaction, relationships and dialogue, integration of context, and the matching of hospital resources to patient and public demands and needs. Subsequently, the outcome will be the resources and reasoning interplay resulting in actions and processes, experiences and knowledge, ‘product’ benefits, emotions, judgements and motivations. Monitoring constitutes an important feedback loop to enable such learnings. The PT aligns the perspectives of the clinical microsystem, improvement science and the service-dominant logic, and has a potential to explain how patient and public involvement in QI interventions might work.
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16.
  • Bergerum, Carolina, 1967-, et al. (författare)
  • Patient involvement in quality improvement - a 'tug of war' or a dialogue in a learning process to improve healthcare?
  • 2020
  • Ingår i: BMC Health Services Research. - : BioMed Central. - 1472-6963. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Co-production and co-design approaches to quality improvement (QI) efforts are gaining momentum in healthcare. Yet, these approaches can be challenging, not least when it comes to patient involvement. The aim of this study was to examine what might influence QI efforts in which patients are involved, as experienced by the patients and the healthcare professionals involved.METHODS: This study involved a qualitative design inspired by the constructivist grounded theory. In one mid-sized Swedish hospital's patient process organisation, data was collected from six QI teams that involved patients in their QI efforts, addressing care paths for patients with transient, chronic and/or multiple parallel diagnoses. Field notes were collected from participant observations during 53 QI team meetings in three of the six patient processes. Individual, semi-structured interviews were conducted with 12 patients and 12 healthcare professionals in all the six QI teams.RESULTS: Patients were involved in QI efforts in different ways. In three of the QI teams, patient representatives attended team meetings regularly. One team consulted patient representatives on a single occasion, one team collected patient preferences structurally from individual interviews with patients, and one team combined interviews and a workshop with patients. The patients' and healthcare professionals' expressions of what might influence the QI efforts involving patients were similar in several ways. QI team members emphasized the importance of organisational structure and culture. Furthermore, they expressed a desire for ongoing interaction between patients and healthcare professionals in healthcare QI.CONCLUSIONS: QI team members recognised continuous dialogue and collective thinking by the sharing of experiences and preferences between patients and healthcare professionals as essential for achieving better matches between healthcare resources and patient needs in their QI efforts. Significant structural and cultural aspects of performing QI in complex hospital organisations were considered to be obstructions to progress. Therefore, to sustain learning and behaviour change through QI efforts at the team level, a deeper understanding of how structural and cultural aspects of QI promote or prevent success appears essential.
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17.
  • Bergerum, Carolina, et al. (författare)
  • 'We are data rich but information poor' : how do patient-reported measures stimulate patient involvement in quality improvement interventions in Swedish hospital departments?
  • 2022
  • Ingår i: BMJ Open Quality. - : BMJ Publishing Group Ltd. - 2399-6641. ; 11:3
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveThis study aimed to investigate if and how patient-reported measures from national and local monitoring stimulate patient involvement in hospital quality improvement (QI) interventions. We were also interested in the factors that influence the level and degree of patient involvement in the QI interventions.MethodsThe study used a qualitative, descriptive design. Inspired by the Framework Method, we created a working analytical framework. Four hospital departments participated in the data collection. Collaborating with a QI leader from each department, we identified the monitoring systems for the patient-reported measures that were used to initiate or evaluate QI interventions. Thereafter, the level and degree of patient involvement and the factors that influenced this involvement were analysed for all QI interventions. Data were mapped in an Excel spreadsheet to analyse connections and differences.ResultsDepartments used patient-reported measures from both national and local monitoring systems to initiate or evaluate their QI interventions. Thirty-one QI interventions were identified and analysed. These interventions were mainly conducted at the direct care and organisational levels. By participating in questionnaires, patients were involved to the degree of consultation. Patients were not involved to the degree of partnership and shared leadership for the identified QI interventions.ConclusionsOverall, hospital departments have limited knowledge regarding patient-reported measures and how they are best applied in QI interventions and how they support improvements. Applying patient-reported measures to hospital QI interventions does not enhance patient involvement beyond the degree of consultation.
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18.
  • Ceasar (Berg), Ina, et al. (författare)
  • Curcumin Promotes A-beta Fibrillation and Reduces Neurotoxicity in Transgenic Drosophila
  • 2012
  • Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 7:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The pathology of Alzheimers disease (AD) is characterized by the presence of extracellular deposits of misfolded and aggregated amyloid-beta (A beta) peptide and intraneuronal accumulation of tangles comprised of hyperphosphorylated Tau protein. For several years, the natural compound curcumin has been proposed to be a candidate for enhanced clearance of toxic A beta amyloid. In this study we have studied the potency of feeding curcumin as a drug candidate to alleviate A beta toxicity in transgenic Drosophila. The longevity as well as the locomotor activity of five different AD model genotypes, measured relative to a control line, showed up to 75% improved lifespan and activity for curcumin fed flies. In contrast to the majority of studies of curcumin effects on amyloid we did not observe any decrease in the amount of A beta deposition following curcumin treatment. Conformation-dependent spectra from p-FTAA, a luminescent conjugated oligothiophene bound to A beta deposits in different Drosophila genotypes over time, indicated accelerated pre-fibrillar to fibril conversion of A beta(1-42) in curcumin treated flies. This finding was supported by in vitro fibrillation assays of recombinant A beta(1-42). Our study shows that curcumin promotes amyloid fibril conversion by reducing the pre-fibrillar/oligomeric species of A beta, resulting in a reduced neurotoxicity in Drosophila.
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19.
  • Crary, John F., et al. (författare)
  • Primary age-related tauopathy (PART) : a common pathology associated with human aging
  • 2014
  • Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 128:6, s. 755-766
  • Tidskriftsartikel (refereegranskat)abstract
    • We recommend a new term, "primary age-related tauopathy" (PART), to describe a pathology that is commonly observed in the brains of aged individuals. Many autopsy studies have reported brains with neurofibrillary tangles (NFTs) that are indistinguishable from those of Alzheimer's disease (AD), in the absence of amyloid (A beta) plaques. For these "NFT+/A beta-aEuroe brains, for which formal criteria for AD neuropathologic changes are not met, the NFTs are mostly restricted to structures in the medial temporal lobe, basal forebrain, brainstem, and olfactory areas (bulb and cortex). Symptoms in persons with PART usually range from normal to amnestic cognitive changes, with only a minority exhibiting profound impairment. Because cognitive impairment is often mild, existing clinicopathologic designations, such as "tangle-only dementia" and "tangle-predominant senile dementia", are imprecise and not appropriate for most subjects. PART is almost universally detectable at autopsy among elderly individuals, yet this pathological process cannot be specifically identified pre-mortem at the present time. Improved biomarkers and tau imaging may enable diagnosis of PART in clinical settings in the future. Indeed, recent studies have identified a common biomarker profile consisting of temporal lobe atrophy and tauopathy without evidence of A beta accumulation. For both researchers and clinicians, a revised nomenclature will raise awareness of this extremely common pathologic change while providing a conceptual foundation for future studies. Prior reports that have elucidated features of the pathologic entity we refer to as PART are discussed, and working neuropathological diagnostic criteria are proposed.
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20.
  • Crespo, Ana, et al. (författare)
  • Phylogenetic generic classification of parmelioid lichens (Parmeliaceae,Ascomycota) based on molecular, morphological and chemical evidence.
  • 2010
  • Ingår i: Taxon. - : John Wiley & Sons. - 0040-0262 .- 1996-8175. ; 59:6, s. 1735-1753
  • Tidskriftsartikel (refereegranskat)abstract
    • Parmelioid lichens are a diverse and ubiquitous group of foliose lichens. Generic delimitation in parmelioid lichens has been in a state of flux since the late 1960s with the segregation of the large, heterogeneous genus Parmelia into numerous smaller genera. Recent molecular phylogenetic studies have demonstrated that some of these new genera were monophyletic, some were not, and others, previously believed to be unrelated, fell within single monophyletic groups, indicating the need for a revision of the generic delimitations. This study aims to give an overview of current knowledge of the major clades of all parmelioid lichens. For this, we assembled a dataset of 762 specimens, including 31 of 33 currently accepted parmelioid genera (and 63 of 84 accepted genera of Parmeliaceae). We performed maximum likelihood and Bayesian analyses of combined datasets including two, three and four loci. Based on these phylogenies and the correlation of morphological and chemical characters that characterize monophyletic groups, we accept 27 genera within nine main clades. We re-circumscribe several genera and reduce Parmelaria to synonymy with Parmotrema. Emodomelanelia Divakar & A. Crespo is described as a new genus (type: E. masonii). Nipponoparmelia (Kurok.) K.H. Moon, Y. Ohmura & Kashiw. ex A. Crespo & al. is elevated to generic rank and 15 new combinations are proposed (in the genera Flavoparmelia, Parmotrema, Myelochroa, Melanelixia and Nipponoparmelia). A short discussion of the accepted genera is provided and remaining challenges and areas requiring additional taxon sampling are identified.
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21.
  • Dewan, Ramita, et al. (författare)
  • Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.
  • 2021
  • Ingår i: Neuron. - : Elsevier BV. - 1097-4199 .- 0896-6273. ; 109:3
  • Tidskriftsartikel (refereegranskat)abstract
    • We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered.
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22.
  • Divakar, Pradeep K., et al. (författare)
  • Evolution of complex symbiotic relationships in a morphologically derived family of lichen-forming fungi
  • 2015
  • Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 208:4, s. 1217-1226
  • Tidskriftsartikel (refereegranskat)abstract
    • We studied the evolutionary history of the Parmeliaceae (Lecanoromycetes, Ascomycota), one of the largest families of lichen-forming fungi with complex and variable morphologies, also including several lichenicolous fungi. We assembled a six-locus data set including nuclear, mitochondrial and low-copy protein-coding genes from 293 operational taxonomic units (OTUs). The lichenicolous lifestyle originated independently three times in lichenized ancestors within Parmeliaceae, and a new generic name is introduced for one of these fungi. In all cases, the independent origins occurred c. 24 million yr ago. Further, we show that the Paleocene, Eocene and Oligocene were key periods when diversification of major lineages within Parmeliaceae occurred, with subsequent radiations occurring primarily during the Oligocene and Miocene. Our phylogenetic hypothesis supports the independent origin of lichenicolous fungi associated with climatic shifts at the Oligocene-Miocene boundary. Moreover, diversification bursts at different times may be crucial factors driving the diversification of Parmeliaceae. Additionally, our study provides novel insight into evolutionary relationships in this large and diverse family of lichen-forming ascomycetes.
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23.
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24.
  • Ekelund, Maria, 1970- (författare)
  • Psoriasis and Temporomandibular Joint Involvement in Juvenile Idiopathic Arthritis (JIA) : A Longitudinal Study of the Nordic JIA Cohort
  • 2020
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Juvenile idiopathic arthritis, JIA, is used as an umbrella term covering a heterogeneous group of chronic arthritis forms in children, many of which have important differences compared to adult arthritis, while others possibly represent similar diseases among children and adults. Classification aims to give a better understanding of the pathogenesis, patterns, disease trajectories and treatment responses. For the juvenile psoriatic arthritis, JPsA, the classification criteria are currently being debated. The distribution of affected joints in JIA differs greatly and it is unknown why some joints appear to be more affected than others. The temporomandibular joint (TMJ) can be affected early in the course of the disease and often the symptoms are mild and without obvious swelling.This thesis has its origin in the Nordic Study Group of Paediatric Rheumatology and the population-based prospective study of 510 children with newly diagnosed JIA included between 1997 and 1999. Totally 440 children were included in the eight-year follow-up, and in the TMJ study 265 patients were examined and underwent cone-beam computed tomography, CBCT, 17 years after onset.After eight years a considerable proportion of the children with definite psoriasis were classified as undifferentiated JIA based on the exclusion criteria in the ILAR classification. Our data also presents the heterogenicity of JPsA and the development over time of clinical variables supporting a psoriatic diathesis, as well as the overlap between JPsA and enthesitis-related arthritis in a group of patients.  We found that extensive symptoms and dysfunctions of the TMJ are seen in JIA 17 years after disease onset, even in patients registered with inactive disease or remission. Individuals with substantial condylar damage on CBCT were found in all JIA categories. The deeper understanding of a chronic disease over time is crucial for research initiatives to improve care as well as for clinical decisions and planning of the health care.Our findings suggest a need for a more appropriate classification of JPsA and also that aspects of TMJ involvement should be included in the general health assessment in JIA.
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25.
  • Eriksson, Mikael, et al. (författare)
  • Needle biopsy through the abdominal wall for the diagnosis of gastrointestinal stromal tumour - Does it increase the risk for tumour cell seeding and recurrence?
  • 2016
  • Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 59, s. 128-133
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Preoperative percutaneous transabdominal wall biopsy may be considered to diagnose gastrointestinal stromal tumour (GIST) and plan preoperative treatment with tyrosine kinase inhibitors when an endoscopic biopsy is not possible. Hypothetically, a transabdominal wall biopsy might lead to cell seeding and conversion of a local GIST to a disseminated one. We investigated the influence of preoperative needle biopsy on survival outcomes.METHODS: We collected the clinical data from hospital case records of the 397 patients who participated in the Scandinavian Sarcoma Group (SSG) XVIII/Arbeitsgemeinschaft Internistische Onkologie (AIO) randomised trial and who had a transabdominal fine needle and/or core needle biopsy carried out prior to study entry. The SSG XVIII/AIO trial compared 1 and 3 years of adjuvant imatinib in a patient population with a high risk of GIST recurrence after macroscopically radical surgery. The primary end-point was recurrence-free survival (RFS), and the secondary end-points included overall survival (OS).RESULTS: A total of 47 (12.0%) out of the 393 patients with data available underwent a percutaneous biopsy. No significant difference in RFS or OS was found between the patients who underwent or did not undergo a percutaneous biopsy either in the entire series or in subpopulation analyses, except for a statistically significant RFS advantage for patients who had a percutaneous biopsy and a tumour ≥10 cm in diameter.CONCLUSION: A preoperative diagnostic percutaneous biopsy of a suspected GIST may not increase the risk for GIST recurrence in a patient population who receive adjuvant imatinib after the biopsy.
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26.
  • Erkapers, Maria, et al. (författare)
  • Patient satisfaction following dental implant treatment with immediate loading in the edentulous atrophic maxilla
  • 2011
  • Ingår i: International Journal of Oral & Maxillofacial Implants. - 0882-2786 .- 1942-4434. ; 26:2, s. 356-364
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: The present study evaluated patient satisfaction using the Oral Health Impact Profile 49 (OHIP-49) questionnaire for patients who received six implants in the severely resorbed maxilla and an implant-supported prosthesis that was delivered within 24 hours after surgery. Materials and Methods: Fifty-one edentulous patients with severe atrophy in the maxilla were included in the study, which was performed at two centers. Six implants were placed in the maxilla and loaded within 24 hours with a provisional restoration. The definitive restorations were delivered 20 to 24 weeks later. Patients were asked to complete the OHIP-49 questionnaire (which includes seven domains representing functional limitation, physical pain, psychologic discomfort, physical disability, psychologic disability, social disability, and handicap) prior to implant placement and on three subsequent occasions. The data were collected and analyzed and OHIP scores were compared over time. Results: Baseline satisfaction scores for the two different centers displayed no statistically significant differences. Treatment resulted in improved total OHIP-49 scores in both centers, with no significant difference between centers. Furthermore, no significant differences were observed in any of the individual pretreatment and posttreatment OHIP-49 domains between centers. All seven domains showed a statistically significant improvement posttreatment. Of the seven domains, social disability and handicap showed the least improvement and had the lowest pretreatment scores, indicating lower significance for these domains compared to the other domains during implant treatment. This study also indicated that domains one to five (functional limitation, physical pain, psychologic discomfort, physical disability, and psychologic disability) are the most important domains in patient satisfaction with implant therapy. Conclusion: Measurement with the OHIP-49 questionnaire displayed that patient satisfaction increases after treatment with a fixed restoration on implants loaded within 24 hours.
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27.
  • Erkapers, Maria, et al. (författare)
  • The influence of immediately loaded implant treatment in the atrophic edentulous maxilla on oral health related quality of life of edentulous patients : 3-year results of a prospective study
  • 2017
  • Ingår i: Head & Face Medicine. - : Springer Science and Business Media LLC. - 1746-160X. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: To evaluate oral health related quality of life (OHQoL) in edentulous patients treated with immediately loaded implants in the maxilla.METHODS: Fifty-one edentulous patients in two centers received six maxillary implants each were loaded within 24 h with provisional restoration. Definitive restoration was delivered 20-24 weeks later. OHQoL was evaluated preoperatively with the Oral Health Impact Profile 49 questionnaire (OHIP-49) and on five subsequent occasions. OHIP-49 includes seven domains representing functional limitation, physical pain, psychological discomfort, physical disability, psychological disability, social disability, and handicap. A reduction in OHIP scores indicated an improved OHQoL.RESULTS: Forty-five patients reached the three-year follow up. OHQoL improved after treatment. A plateau of OHQoL improvement was observed at 12 months after surgery. The seven domains improved at different pace, 12 weeks to 12 months after treatment. OHIP showed continuously low scores with no significant changes at consecutive visits 12 months to three years after treatment. Dental status with removable prosthesis in the mandible had a negative impact on OHQoL prior to and during treatment, but did not affect OHQoL after permanent restoration was placed. Patients age or gender did not affect OHQoL.CONCLUSIONS: Patients with edentulous maxilla who received prosthetic rehabilitation on immediately loaded implants experienced the highest improved OHQoL 12 months after implant installation. Quality of life related to oral health continued to be high after three years. Edentulous patients with atrophy of the maxilla experience an improved OHQoL after implant treatment with immediate loading protocol.TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00711022 .
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28.
  • He, Anna, et al. (författare)
  • Timing of high-efficacy therapy for multiple sclerosis: a retrospective observational cohort study.
  • 2020
  • Ingår i: The Lancet. Neurology. - 1474-4465. ; 19:4, s. 307-316
  • Tidskriftsartikel (refereegranskat)abstract
    • High-efficacy therapies in multiple sclerosis are traditionally used after unsuccessful treatment with first-line disease modifying therapies. We hypothesised that early commencement of high-efficacy therapy would be associated with reduced long-term disability. We therefore aimed to compare long-term disability outcomes between patients who started high-efficacy therapies within 2 years of disease onset with those who started 4-6 years after disease onset.In this retrospective international observational study, we obtained data from the MSBase registry and the Swedish MS registry, which prospectively collect patient data that are specific to multiple sclerosis as part of routine clinical care. We identified adult patients (aged ≥18 years) with relapsing-remitting multiple sclerosis, with at least 6 years of follow-up since disease onset, and who started the high-efficacy therapy (rituximab, ocrelizumab, mitoxantrone, alemtuzumab, or natalizumab) either 0-2 years (early) or 4-6 years (late) after clinical disease onset. We matched patients in the early and late groups using propensity scores calculated on the basis of their baseline clinical and demographic data. The primary outcome was disability, measured with the Expanded Disability Status Score (EDSS; an ordinal scale of 0-10, with higher scores indicating increased disability), at 6-10 years after disease onset, assessed with a linear mixed-effects model.We identified 6149 patients in the MSBase registry who had been given high-efficacy therapy, with data collected between Jan 1, 1975, and April 13, 2017, and 2626 patients in the Swedish MS Registry, with data collected between Dec 10, 1997, and Sept 16, 2019. Of whom, 308 in the MSBase registry and 236 in the Swedish MS registry were eligible for inclusion. 277 (51%) of 544 patients commenced therapy early and 267 (49%) commenced therapy late. For the primary analysis, we matched 213 patients in the early treatment group with 253 in the late treatment group. At baseline, the mean EDSS score was 2·2 (SD 1·2) in the early group and 2·1 (SD 1·2) in the late group. Median follow-up time for matched patients was 7·8 years (IQR 6·7-8·9). In the sixth year after disease onset, the mean EDSS score was 2·2 (SD 1·6) in the early group compared with 2·9 (SD 1·8) in the late group (p<0·0001). This difference persisted throughout each year of follow-up until the tenth year after disease onset (mean EDSS score 2·3 [SD 1·8] vs 3·5 [SD 2·1]; p<0·0001), with a difference between groups of -0·98 (95% CI -1·51 to -0·45; p<0·0001, adjusted for proportion of time on any disease-modifying therapy) across the 6-10 year follow-up period.High-efficacy therapy commenced within 2 years of disease onset is associated with less disability after 6-10 years than when commenced later in the disease course. This finding can inform decisions regarding optimal sequence and timing of multiple sclerosis therapy.National Health and Medical Research Council Australia and MS Society UK.
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29.
  • Henrikson, Thor, et al. (författare)
  • Can orthodontic treatment improve mastication? : A controlled, prospective and longitudinal study
  • 2009
  • Ingår i: Swedish Dental Journal. - : Swedish dental association. - 0347-9994. ; 33:2, s. 59-65
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To prospectively and longitudinally evaluate the self-perceived masticatory ability and the tested masticatory efficiency in orthodontically treated and untreated groups. DESIGN: Prospective observational cohort. SUBJECTS AND METHODS: Three groups of age matched adolescent girls were included. Sixty-five Class II subjects received orthodontic treatment fixed appliance treatment (Orthodontic group), 58 subjects were orthodontically untreated (Class II group) and 60 subjects had a normal occlusion (Normal group).The self-perceived masticatory ability was assessed on a visual analogue scale while the masticatory efficiency was evaluated with a masticatory efficiency test using round silicon tablets. Registrations were performed at the start and after two years when all subjects in the Orthodontic group had finished orthodontic treatment. RESULTS: Over the two-year period the self-perceived masticatory ability increased significantly in the Orthodontic group. After treatment, the Orthodontic group perceived their masticatory ability as high as the Normal group did. The masticatory efficiency increased significantly, during the two years, in all three groups. However,the normal occlusion group presented a significantly better masticatory efficiency than both the Orthodontic group and the Class II group on both registrations. CONCLUSIONS: Orthodontic treatment was beneficial for the self-perceived masticatory ability. The masticatory efficiency increases with age during adolescence. Normal occlusion subjects had a better masticatory efficiency than subjects with orthodontically treated as well as untreated Class II malocclusion.
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30.
  • Hoffmann-Vold, Anna Maria, et al. (författare)
  • CCL21 as a Potential Serum Biomarker for Pulmonary Arterial Hypertension in Systemic Sclerosis
  • 2018
  • Ingår i: Arthritis and Rheumatology. - : Wiley. - 2326-5191. ; 70:10, s. 1644-1653
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Systemic sclerosis (SSc) is a major cause of pulmonary arterial hypertension (PAH). Murine models indicate key roles for chemokines CCL19 and CCL21 and their receptor CCR7 in lung inflammation leading to PAH. The objective of this study was to assess the chemokine CCL19–CCL21 axis in patients with SSc-related PAH. Methods: Serum samples obtained from 2 independent prospective SSc cohorts (n = 326), patients with idiopathic PAH (n = 12), and healthy control subjects (n = 100) were analyzed for CCL19/CCL21 levels, by enzyme-linked immunosorbent assay. The levels were defined as either high or low, using the mean + 2 SD value in controls as the cutoff value. Risk stratification at the time of PAH diagnosis and PAH-related events were performed. Descriptive and Cox regression analyses were conducted. Results: CCL21 levels were higher in patients with SSc compared with controls and were elevated prior to the diagnosis of PAH. PAH was more frequent in patients with high CCL21 levels (≥0.4 ng/ml) than in those with low CCL21 levels (33.3% versus 5.3% [P < 0.001]). In multivariate analyses, CCL21 was associated with PAH (hazard ratio [HR] 5.1, 95% CI 2.39–10.76 [P < 0.001]) and occurrence of PAH-related events (HR 4.7, 95% CI 2.12–10.46, P < 0.001). Risk stratification at the time of PAH diagnosis alone did not predict PAH-related events. However, when risk at diagnosis was combined with high or low CCL21 level, there was a significant predictive effect (HR 1.3, 95% CI 1.03–1.60 [P = 0.027]). A high CCL21 level was associated with decreased survival (P < 0.001). Conclusion: CCL21 appears to be a promising marker for predicting the risk of SSc-related PAH and PAH progression. CCL21 may be part of a dysregulated immune pathway linked to the development of lung vascular damage in SSc.
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31.
  • Hudson, Lawrence N., et al. (författare)
  • The PREDICTS database : a global database of how local terrestrial biodiversity responds to human impacts
  • 2014
  • Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 4:24, s. 4701-4735
  • Tidskriftsartikel (refereegranskat)abstract
    • Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - ). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
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32.
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33.
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34.
  • Jonson, Maria (författare)
  • Investigating Amyloid β toxicity in Drosophila melanogaster
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • In this thesis Drosophila melanogaster (the fruit fly) has been used as a model organism to study the aggregation and toxic properties of the human amyloid β (Aβ) peptide involved in the onset of Alzheimer's disease (AD). AD is one of many misfolding diseases where the important event of a protein to adopt its’ specific three-dimensional structure has failed, leading to aggregation and formation of characteristic amyloid fibrils. AD has a complex pathology and probably reflects a variety of related molecular and cellular abnormalities, however, the most apparent common denominator so far is abnormal Amyloid-β precursor protein (APP) processing, resulting in a pool of various Aβ-peptides. In AD, the Aβ peptide misfolds, aggregates and forms amyloid plaques in the brain of patients, resulting in progressive neurodegeneration that eventually leads to death.By expressing the human Aβ protein in the fly, we have studied the mechanisms and toxicity of the aggregation in detail and how different cell types in the fly are affected. We have also used this model to investigate the effect of potential drugs that can have a positive impact on disease progression. In the first and second work in this thesis, we have, in a systematic way, proved that the length of the Aβ-peptide is essential for its toxicity and propensity to aggregate. If the peptide expressed ends at amino acid 42 it is extremely toxic to the fly nervous system. However, this toxicity can be completely abolished by expressing a variant that is shorter than 42 amino acids (1-37 to 1-41 aa), or be significantly reduced by expressing a longer variant (1-43 aa). Toxicity can be partly mitigated in trans by co-expressing the 1-42 variant with a 1-38 variant. This supports the theory that the disease progression could be inhibited if the formation of Aβ 1-42 is decreased. In the third work we demonstrate that amyloid aggregates can be found in various cell types of Drosophila, however, the toxicity seem to be selective to neurons. Our results indicate that the aggregates of glial expressing flies have a more mature structure, which appear to be less toxic. This also suggests that glial cells might spread Aβ aggregates without being harmed. The last work in this thesis investigates how curcumin (turmeric) can affect Aβ aggregation and toxicity. Curcumin appears to shift the equilibrium between the less stableaggregates and mature fibers toward the final stage resulting in an improved lifespan for treated flies.In summary, this thesis demonstrates that the toxicity of Aβ in Drosophila is highly dependent on the Aβ variant expressed, the structure of the protein aggregates and which cell type that expresses the protein. We have also shed light on the potential of using Drosophila when it comes to examining possible therapeutic substances as a tool for drug discovery.
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35.
  • Jonsson, Maria, et al. (författare)
  • Aggregated Aβ1-42 Is Selectively Toxic for Neurons, Whereas Glial Cells Produce Mature Fibrils with Low Toxicity in Drosophila
  • 2018
  • Ingår i: Cell Chemical Biology. - Cambridge, United States : Elsevier BV. - 2451-9456 .- 2451-9448. ; 25:5
  • Tidskriftsartikel (refereegranskat)abstract
    • The basis for selective vulnerability of certain cell types for misfolded proteins (MPs) in neurodegenerative diseases is largely unknown. This knowledge is crucial for understanding disease progression in relation to MPs spreading in the CNS. We assessed this issue in Drosophila by cell-specific expression of human Aβ1-42 associated with Alzheimer's disease. Expression of Aβ1-42 in various neurons resulted in concentration-dependent severe neurodegenerative phenotypes, and intraneuronal ring-tangle-like aggregates with immature fibril properties when analyzed by aggregate-specific ligands. Unexpectedly, expression of Aβ1-42 from a pan-glial driver produced a mild phenotype despite massive brain load of Aβ1-42 aggregates, even higher than in the strongest neuronal driver. Glial cells formed more mature fibrous aggregates, morphologically distinct from aggregates found in neurons, and was mainly extracellular. Our findings implicate that Aβ1-42 cytotoxicity is both cell and aggregate morphotype dependent. Jonson et al. used transgenic Drosophila to understand cell-specific response to protein aggregates in neurodegenerative disease. They demonstrate that the Alzheimer-associated peptide Aβ1-42 form various amyloid structures with different toxic properties when expressed in different cell types of the brain. © 2018 Elsevier Ltd
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36.
  • Jonsson, Maria, et al. (författare)
  • Systematic A beta Analysis in Drosophila Reveals High Toxicity for the 1-42, 3-42 and 11-42 Peptides, and Emphasizes N- and C-Terminal Residues
  • 2015
  • Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 10:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Brain amyloid plaques are a hallmark of Alzheimers disease (AD), and primarily consist of aggregated A beta peptides. While A beta 1-40 and A beta 1-42 are the most abundant, a number of other A beta peptides have also been identified. Studies have indicated differential toxicity for these various A beta peptides, but in vivo toxicity has not been systematically tested. To address this issue, we generated improved transgenic Drosophila UAS strains expressing 11 pertinent A beta peptides. UAS transgenic flies were generated by identical chromosomal insertion, hence removing any transgenic position effects, and crossed to a novel and robust Gal4 driver line. Using this improved Gal4/UAS set-up, survival and activity assays revealed that A beta 1-42 severely shortens lifespan and reduces activity. N-terminal truncated peptides were quite toxic, with 3-42 similar to 1-42, while 11-42 showed a pronounced but less severe phenotype. N-terminal mutations in 3-42 (E3A) or 11-42 (E11A) resulted in reduced toxicity for 11-42, and reduced aggregation for both variants. Strikingly, C-terminal truncation of A beta (1-41, -40, -39, -38, -37) were non-toxic. In contrast, C-terminal extension to 1-43 resulted in reduced lifespan and activity, but not to the same extent as 1-42. Mutating residue 42 in 1-42 (A42D, A42R and A42W) greatly reduced A beta accumulation and toxicity. Histological and biochemical analysis revealed strong correlation between in vivo toxicity and brain A beta aggregate load, as well as amount of insoluble A beta. This systematic Drosophila in vivo and in vitro analysis reveals crucial N- and C-terminal specificity for A beta neurotoxicity and aggregation, and underscores the importance of residues 1-10 and E11, as well as a pivotal role of A42.
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37.
  • Joppe, Marion, et al. (författare)
  • Knowledge
  • 2022
  • Ingår i: Teaching Tourism : Innovative, Values-based Learning Experiences for Transformative Practices - Innovative, Values-based Learning Experiences for Transformative Practices. - 9781800374553 - 9781800374560 ; , s. 96-106
  • Bokkapitel (refereegranskat)
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38.
  • Joppe, Marion, et al. (författare)
  • Knowledge
  • 2022
  • Ingår i: Teaching Tourism. - : Edward Elgar Publishing. - 9781800374553 ; , s. 96-106
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
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39.
  • Kontny, Frederic, et al. (författare)
  • Pentraxin-3 vs C-reactive protein and other prognostic biomarkers in acute coronary syndrome : A substudy of the Platelet Inhibition and Patients Outcomes (PLATO) trial
  • 2020
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 2048-8726 .- 2048-8734. ; 9:4, s. 313-322
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: We investigated the dynamics, associations with patient characteristics, other biomarkers, and clinical outcomes of pentraxin 3 in acute coronary syndrome.METHODS AND RESULTS: In multivariate analyses, pentraxin 3 measured in 5154 patients randomised in the Platelet Inhibition and Patients Outcomes (PLATO) trial (NCT00391872) was compared with leukocytes, high-sensitivity C-reactive protein, interleukin-6, cystatin C, N-terminal prohormone brain natriuretic peptide, high-sensitivity troponin T and growth differentiation factor 15 concerning prediction of clinical outcome. Pentraxin 3 peaked earlier than high-sensitivity C-reactive protein and was more strongly correlated with N-terminal prohormone brain natriuretic peptide and high-sensitivity troponin T than with high-sensitivity C-reactive protein. The frequency of cardiovascular death, spontaneous myocardial infarction or stroke by quartiles of pentraxin 3 at admission was 6.1%, 7.3%, 9.7% and 10.7%, respectively ( p<0.0001). The hazard ratio per 50% increase of pentraxin 3 was 1.13 (95% confidence interval: 1.07-1.19), p<0.0001. This association remained significant after stepwise adjustments for leukocytes/high-sensitivity C-reactive protein (1.09 (1.02-1.15)), p=0.009, interleukin-6 (1.07 (1.01-1.14)), p=0.026, and cystatin C (1.07 (1.00-1.13)), p=0.044, but not after adjustment for N-terminal prohormone brain natriuretic peptide, high-sensitivity troponin T and growth differentiation factor 15. Admission pentraxin 3 was also associated with several of the individual endpoint components (cardiovascular death/spontaneous myocardial infarction; p=0.008, cardiovascular death; p=0.026, and spontaneous myocardial infarction; p=0.017), but not with stroke. Pentraxin 3 measured in the chronic phase (i.e. at one month) was still predictive of the composite endpoint in univariate analysis (1.12 (1.04-1.20) per 50% increase) p=0.0024, but not after adjustment for the other biomarkers.CONCLUSION: Admission level of pentraxin 3 is a modestly stronger predictor than high-sensitivity C-reactive protein and interleukin-6, but not than N-terminal prohormone brain natriuretic peptide or high-sensitivity troponin T, concerning cardiovascular outcome in acute coronary syndrome. Pentraxin 3 is more strongly correlated with N-terminal prohormone brain natriuretic peptide and high-sensitivity troponin T than with high-sensitivity C-reactive protein.
  •  
40.
  • Losada-Perez, Maria, et al. (författare)
  • Klumpfuss controls FMRFamide expression by enabling BMP signaling within the NB5-6 lineage
  • 2013
  • Ingår i: Development. - : Company of Biologists. - 0950-1991 .- 1477-9129. ; 140:10, s. 2181-2189
  • Tidskriftsartikel (refereegranskat)abstract
    • A number of transcription factors that are expressed within most, if not all, embryonic neuroblast (NB) lineages participate in neural subtype specification. Some have been extensively studied in several NB lineages (e.g. components of the temporal gene cascade) whereas others only within specific NB lineages. To what extent they function in other lineages remains unknown. Klumpfuss (Klu), the Drosophila ortholog of the mammalian Wilms tumor 1 (WT1) protein, is one such transcription factor. Studies in the NB4-2 lineage have suggested that Klu functions to ensure that the two ganglion mother cells (GMCs) in this embryonic NB lineage acquire different fates. Owing to limited lineage marker availability, these observations were made only for the NB4-2 lineage. Recent findings reveal that Klu is necessary for larval neuroblast growth and self-renewal. We have extended the study of Klu to the well-known embryonic NB5-6T lineage and describe a novel role for Klu in the Drosophila embryonic CNS. Our results demonstrate that Klu is expressed specifically in the postmitotic Ap4/FMRFa neuron, promoting its differentiation through the initiation of BMP signaling. Our findings indicate a pleiotropic function of Klu in Ap cluster specification in general and particularly in Ap4 neuron differentiation, indicating that Klu is a multitasking transcription factor. Finally, our studies indicate that a transitory downregulation of klu is crucial for the specification of the Ap4/FMRFa neuron. Similar to WT1, klu seems to have either self-renewal or differentiation-promoting functions, depending on the developmental context.
  •  
41.
  • Loth, Daan W, et al. (författare)
  • Genome-wide association analysis identifies six new loci associated with forced vital capacity
  • 2014
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46, s. 669-677
  • Tidskriftsartikel (refereegranskat)abstract
    • Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
  •  
42.
  • Lundberg, Olle, et al. (författare)
  • The role of welfare state principles and generosity in social policy programmes for public health : an international comparative study
  • 2008
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 372:9650, s. 1633-1640
  • Tidskriftsartikel (refereegranskat)abstract
    •  Background Many important social determinants of health are also the focus for social policies. Welfare states contribute to the resources available for their citizens through cash transfer programmes and subsidised services. Although all rich nations have welfare programmes, there are clear cross-national differences with respect to their design and generosity These differences are evident in national variations in poverty rates, especially among children and elderly people. We investigated to what extent variations in family and pension policies are linked to infant mortality and old-age excess mortality. Methods Infant mortality rates and old-age excess mortality rates were analysed in relation to social policy characteristics and generosity. We did pooled cross-sectional time-series analyses of 18 OECD (Organisation for Economic Co-operation and Development) countries during the period 1970-2000 for family policies and 1950-2000 for pension policies. Findings Increased generosity in family policies that support dual-earner families is linked with lower infant mortality rates, whereas the generosity in family policies that support more traditional families with gainfully employed men and homemaking women is not. An increase by one percentage point in dual-earner support lowers infant mortality by 0.04 deaths per 1000 births. Generosity in basic security type of pensions is linked to lower old-age excess mortality, whereas the generosity of earnings-related income security pensions is not. An increase by one percentage point in basic security pensions is associated with a decrease in the old age excess mortality by 0.02 for men as well as for women. Interpretation The ways in which social policies are designed, as well as their generosity, are important for health because of the increase in resources that social policies entail. Hence, social policies are of major importance for how we can tackle the social determinants of health.
  •  
43.
  • Magnusson, Kerstin, et al. (författare)
  • Scrubbers: Closing the loop; Activity 3. Task 2; Risk assessment of marine exhaust gas scrubber water.
  • 2018
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • In response to regulations on permitted levels of sulphur emissions from ships an increasing amount of ships are expected to become equipped with exhaust gas cleaning systems, so called scrubbers. The use of scrubbers makes it possible to continue to use high sulphur fuel oil on board. In the scrubbers, the exhaust gases are washed with a scrubber fluid aiming at reducing levels of sulphur dioxide. The fluid passes the exhaust gas once (“open loop scrubber”) or is recirculated (“closed loop scrubber”). This study investigates the potential impact of the discharges from open and closed loop scrubbers on marine ecosystems. Samples were taken of effluent water from ships with closed loop and open loop scrubbers. The water from closed loop systems is treated before discharge to the marine environment. The waters were tested for toxicity using experimental studies with field collected zooplankton and bottom-dwelling blue mussels. Zooplankton were found to be more sensitive than mussels. A subsequent risk assessment based on the toxicity results and data on discharged volumes together with a simple and static model on mixing in sea water showed that the issue needs further attention specially to protect sensitive and enclosed areas with heavy ship traffic.
  •  
44.
  • Mazzocato, Pamela, et al. (författare)
  • Unpacking the key components of a programme to improve the timeliness of hip-fracture care : a mixed-methods case study
  • 2015
  • Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : Springer Science and Business Media LLC. - 1757-7241. ; 23, s. 1-12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Delay to surgery for patients with hip fracture is associated with higher incidence of post-operative complications, prolonged recovery and length of stay, and increased mortality. Therefore, many health care organisations launch improvement programmes to reduce the wait for surgery. The heterogeneous application of similar methods, and the multifaceted nature of the interventions, constrain the understanding of which method works, when, and how. In complex acute care settings, another concern is how changes for one patient group influence the care for other groups. We therefore set out to analyse how multiple components of hip-fracture improvement efforts aimed to reduce the time to surgery influenced that time both for hip-fracture patients and for other acute surgical orthopaedic inpatients.Methods: This study is an observational mixed-methods single case study of improvement efforts at a Swedish acute care hospital, which triangulates control chart analysis of process performance data over a five year period with interview, document, and non-participant observation data. Results: The improvement efforts led to an increase in the monthly percentage of hip-fracture patients operated within 24 h of admission from an average of 47 % to 83 %, with performance predictably ranging between 67 % and 98 % if the process continues unchanged. Meanwhile, no significant changes in lead time to surgery for other acute surgical orthopaedic inpatients were observed. Interview data indicated that multiple intervention components contributed to making the process more reliable. The triangulation of qualitative and quantitative data, however, indicated that key changes that improved performance were the creation of a process improvement team and having an experienced clinician coordinate demand and supply of surgical services daily and enhance pre-operative patient preparation.Conclusions: Timeliness of surgery for patients with hip fracture in a complex hospital setting can be substantially improved without displacing other patient groups, by involving staff in improvement efforts and actively managing acute surgical procedures.
  •  
45.
  • Moayyeri, Alireza, et al. (författare)
  • Genetic determinants of heel bone properties : genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium
  • 2014
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:11, s. 3054-3068
  • Tidskriftsartikel (refereegranskat)abstract
    • Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 x 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 x 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 x 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.
  •  
46.
  • Myklebust, Thor, et al. (författare)
  • Data Safety, Sources, and Data Flow in the Offshore Industry
  • 2021
  • Ingår i: Proceedings of the 31st European Safety and Reliability Conference (ESREL 2021). - Singapore : Research Publishing. - 9789811820168 ; , s. 1538-1545
  • Konferensbidrag (refereegranskat)abstract
    • Digitization may provide increased access to and more efficient use of real-time and historical data, internally as well as externally in an organization. However, when information from industrial control systems (ICS) becomes more available in office IT systems and in the “cloud”, ICS systems may become more vulnerable and attractive targets for cyberattacks. We have investigated data safety in ICS in the Norwegian offshore sector when data is processed from ICS to the office network. The work is mainly based on document review and nine interviews with selected oil companies, rig companies and service providers of operational data. The paper addresses strengths and threats related to data safety with emphasis on (1) Data sources and data flow, (2) Safety and security of data, (3) Data cleaning and processing, (4) Contextualization, (5) Validation, and (6) Quality assurance. We also discuss shortcomings for functional safety in current standards such as IEC 61508 and IEC 61511 and standard series for security, IEC 62443. It is a major challenge for the industry that there are no good international standards and guidelines that define the relevant terminology across IT systems and ICS. Future work should address data safety challenges when applying artificial intelligence and machine learning in ICS systems.
  •  
47.
  • Myklebust, Thor, et al. (författare)
  • Datakvalitet ved digitalisering i petroleumssektoren : IKT-sikkerhet – Robusthet i petroleumssektoren 2020
  • 2021
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Formålet med denne rapporten er å undersøke hvilke datakilder og data som benyttes iindustrielle IKT-systemer og hvordan data behandles og prosesseres før de gjørestilgjengelig i kontornettet. Styrker og sårbarheter knyttet til datakvalitet og sikring av datablir diskutert.Denne rapporten er en av seks SINTEF-rapporter fra prosjektet: "IKT-sikkerhet – Robustheti petroleumssektoren 2020". Prosjektet har innhentet kunnskap om risiko, sårbarheter ogIKT-sikkerhet for industrielle IKT-systemer.
  •  
48.
  • Norum, Hilde M, et al. (författare)
  • Circulating delta-like Notch ligand 1 is correlated with cardiac allograft vasculopathy and suppressed in heart transplant recipients on everolimus-based immunosuppression.
  • 2019
  • Ingår i: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. - : Elsevier BV. - 1600-6143. ; 19:4, s. 1050-1060
  • Tidskriftsartikel (refereegranskat)abstract
    • Cardiac allograft vasculopathy (CAV) causes heart failure after heart transplantation (HTx), but its pathogenesis is incompletely understood. Notch signaling, possibly modulated by everolimus (EVR), is essential for processes involved in CAV. We hypothesized that circulating Notch ligands would be dysregulated after HTx. We studied circulating delta-like Notch ligand 1 (DLL1) and periostin (POSTN) and CAV in de novo HTx recipients (n=70) randomized to standard or EVR-based, calcineurin inhibitor-free immunosuppression and in maintenance HTx recipients (n=41). Compared to healthy controls, plasma DLL1 and POSTN were elevated in de novo (P<.01; P<.001) and maintenance HTx recipients (P<.001; P<.01). Use of EVR was associated with a treatment effect for DLL1. For de novo HTx recipients, a change in DLL1 correlated with a change in CAV at 1 (P=.021) and 3years (P=.005). In vitro, activation of T cells increased DLL1 secretion, attenuated by EVR. In vitro data suggest that also endothelial cells and vascular smooth muscle cells (VSMCs) could contribute to circulating DLL1. Immunostaining of myocardial specimens showed colocalization of DLL1 with T cells, endothelial cells, and VSMCs. Our findings suggest a role of DLL1 in CAV progression, and that the beneficial effect of EVR on CAV could reflect a suppressive effect on DLL1. Trial registration numbers-SCHEDULE trial: ClinicalTrials.gov NCT01266148; NOCTET trial: ClinicalTrials.gov NCT00377962.
  •  
49.
  • Palma, Guillermo, et al. (författare)
  • Determining similarity of scientific entities in annotation datasets.
  • 2015
  • Ingår i: Database. - : Oxford University Press (OUP). - 1758-0463. ; 2015
  • Tidskriftsartikel (refereegranskat)abstract
    • Linked Open Data initiatives have made available a diversity of scientific collections where scientists have annotated entities in the datasets with controlled vocabulary terms from ontologies. Annotations encode scientific knowledge, which is captured in annotation datasets. Determining relatedness between annotated entities becomes a building block for pattern mining, e.g. identifying drug-drug relationships may depend on the similarity of the targets that interact with each drug. A diversity of similarity measures has been proposed in the literature to compute relatedness between a pair of entities. Each measure exploits some knowledge including the name, function, relationships with other entities, taxonomic neighborhood and semantic knowledge. We propose a novel general-purpose annotation similarity measure called 'AnnSim' that measures the relatedness between two entities based on the similarity of their annotations. We model AnnSim as a 1-1 maximum weight bipartite match and exploit properties of existing solvers to provide an efficient solution. We empirically study the performance of AnnSim on real-world datasets of drugs and disease associations from clinical trials and relationships between drugs and (genomic) targets. Using baselines that include a variety of measures, we identify where AnnSim can provide a deeper understanding of the semantics underlying the relatedness of a pair of entities or where it could lead to predicting new links or identifying potential novel patterns. Although AnnSim does not exploit knowledge or properties of a particular domain, its performance compares well with a variety of state-of-the-art domain-specific measures. Database URL: http://www.yeastgenome.org/
  •  
50.
  • Rafaeva, Maria, et al. (författare)
  • Modeling Metastatic Colonization in a Decellularized Organ Scaffold-Based Perfusion Bioreactor
  • 2022
  • Ingår i: Advanced healthcare materials. - : Wiley. - 2192-2640 .- 2192-2659. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Metastatic cancer spread is responsible for most cancer-related deaths. To colonize a new organ, invading cells adapt to, and remodel, the local extracellular matrix (ECM), a network of proteins and proteoglycans underpinning all tissues, and a critical regulator of homeostasis and disease. However, there is a major lack in tools to study cancer cell behavior within native 3D ECM. Here, an in-house designed bioreactor, where mouse organ ECM scaffolds are perfused and populated with cells that are challenged to colonize it, is presented. Using a specialized bioreactor chamber, it is possible to monitor cell behavior microscopically (e.g., proliferation, migration) within the organ scaffold. Cancer cells in this system recapitulate cell signaling observed in vivo and remodel complex native ECM. Moreover, the bioreactors are compatible with co-culturing cell types of different genetic origin comprising the normal and tumor microenvironment. This degree of experimental flexibility in an organ-specific and 3D context, opens new possibilities to study cell–cell and cell–ECM interplay and to model diseases in a controllable organ-specific system ex vivo.
  •  
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