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| 8. |
- Arking, D. E., et al.
(författare)
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Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
- 2014
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:8, s. 826-836
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Tidskriftsartikel (refereegranskat)abstract
- The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼ 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. © 2014 Nature America, Inc.
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| 12. |
- Fernandez, J. L. Abelleira, et al.
(författare)
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A Large Hadron Electron Collider at CERN
- 2012
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Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 39:7
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Tidskriftsartikel (refereegranskat)
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| 13. |
- Zhang, W., et al.
(författare)
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EULAR evidence-based recommendations for the diagnosis of hand osteoarthritis: report of a task force of ESCISIT
- 2009
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 68:1, s. 8-17
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Forskningsöversikt (refereegranskat)abstract
- Objectives: To develop evidence-based recommendations for the diagnosis of hand osteoarthritis (OA). Methods: The multidisciplinary guideline development group, representing 15 European countries, generated 10 key propositions regarding diagnosis using a Delphi consensus approach. For each recommendation, research evidence was searched for systematically. Whenever possible, the sensitivity, specificity and likelihood ratio (LR) were calculated; relative risk and odds ratios were estimated for risk factors for hand OA. Quality of evidence was categorised using the European League Against Rheumatism (EULAR) hierarchy, and strength of recommendation was assessed by the EULAR visual analogue scale. Results: Diagnostic topics included clinical manifestations, radiographic features, subgroups, differential diagnosis, laboratory tests, risk factors and comorbidities. The sensitivity, specificity and LR varied between tests depending upon the cut-off level, gold standard and controls. Overall, no single test could be used to define hand OA on its own (LR,10) but a composite of the tests greatly increased the chance of the diagnosis. The probability of a subject having hand OA was 20% when Heberden nodes alone were present, but this increased to 88% when in addition the subject was over 40 years old, had a family history of nodes and had joint space narrowing in any finger joint. Conclusion: Ten key recommendations for diagnosis of hand OA were developed using research evidence and expert consensus. Diagnosis of hand OA should be based on assessment of a composite of features.
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| 14. |
- Zhang, W., et al.
(författare)
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EULAR evidence-based recommendations for the diagnosis of knee osteoarthritis
- 2010
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 69:3, s. 483-489
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Forskningsöversikt (refereegranskat)abstract
- Objective To develop evidence-based recommendations for the diagnosis of knee osteoarthritis (OA). Methods The multidisciplinary guideline development group, representing 12 European countries, generated 10 key propositions regarding diagnosis using a Delphi consensus approach. For each recommendation, research evidence was searched systematically. Whenever possible, the sensitivity, specificity and likelihood ratio were calculated for individual diagnostic indicators and a diagnostic ladder was developed using Bayes' method. Secondary analyses were undertaken to test directly the recommendations using multiple predictive models in two populations from the UK and the Netherlands. Strength of recommendation was assessed by the EULAR visual analogue scale. Results Recommendations covered the definition of knee OA and its risk factors, subsets, typical symptoms and signs, the use of imaging and laboratory tests and differential diagnosis. Three symptoms (persistent knee pain, limited morning stiffness and reduced function) and three signs (crepitus, restricted movement and bony enlargement) appeared to be the most useful. Assuming a 12.5% background prevalence of knee OA in adults aged >= 45 years, the estimated probability of having radiographic knee OA increased with increasing number of positive features, to 99% when all six symptoms and signs were present. The performance of the recommendations in the study populations varied according to the definition of knee OA, background risk and number of tests applied. Conclusion 10 key recommendations for diagnosis of knee OA were developed using both research evidence and expert consensus. Although there is no agreed reference standard, thorough clinical assessment alone can provide a confident rule-in diagnosis.
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- Forsyth, C., et al.
(författare)
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Temporal evolution and electric potential structure of the auroral acceleration region from multispacecraft measurements
- 2012
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 117:12, s. A12203-
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Tidskriftsartikel (refereegranskat)abstract
- Bright aurorae can be excited by the acceleration of electrons into the atmosphere in violation of ideal magnetohydrodynamics. Modeling studies predict that the accelerating electric potential consists of electric double layers at the boundaries of an acceleration region but observations suggest that particle acceleration occurs throughout this region. Using multispacecraft observations from Cluster, we have examined two upward current regions on 14 December 2009. Our observations show that the potential difference below C4 and C3 changed by up to 1.7 kV between their respective crossings, which were separated by 150 s. The field-aligned current density observed by C3 was also larger than that observed by C4. The potential drop above C3 and C4 was approximately the same in both crossings. Using a novel technique of quantitively comparing the electron spectra measured by Cluster 1 and 3, which were separated in altitude, we determine when these spacecraft made effectively magnetically conjugate observations, and we use these conjugate observations to determine the instantaneous distribution of the potential drop in the AAR. Our observations show that an average of 15% of the potential drop in the AAR was located between C1 at 6235 km and C3 at 4685 km altitude, with a maximum potential drop between the spacecraft of 500 V, and that the majority of the potential drop was below C3. Assuming a spatial invariance along the length of the upward current region, we discuss these observations in terms of temporal changes and the vertical structure of the electrostatic potential drop and in the context of existing models and previous single- and multispacecraft observations.
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- Storey, Jennifer, et al.
(författare)
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Utilization and implications of the Static-99 in practice
- 2012
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Ingår i: Sexual abuse. A Journal of Research and Treatment. - : SAGE Publications. - 1079-0632 .- 1573-286X. ; 24:3, s. 289-302
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Tidskriftsartikel (refereegranskat)abstract
- The Static-99 is the most commonly used risk assessment instrument for sexual violence in North America and its results can affect highly consequential decisions made in the criminal and civil justice systems. Despite its influence, few studies have systematically examined how the Static-99 is used by clinicians in practice. The current study compares the Static-99 ratings of clinicians to those of researchers for 100 adult males who completed an outpatient sex offender treatment program and were followed up over an average of about 4 years. Results showed good agreement between the ratings of clinicians and researchers for total scores on the Static-99, as well as for most individual items. Ratings by clinicians tended to be slightly lower than those made by researchers. The predictive validity of ratings made by clinicians and researchers was very similar and moderate in terms of effect size. In 30 cases, clinicians used discretion to "override" or adjust the Static-99 ratings when making final risk judgments, but the predictive validity of the clinical adjusted ratings was worse than that of the original Static-99 ratings made by clinicians. The need for quality assurance and training are discussed along with the need for clear empirically supported guidelines regarding overrides. © The Author(s) 2012.
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| 20. |
- Almet, A, et al.
(författare)
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A roadmap for the human skin cell atlas
- 2023
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Ingår i: JOURNAL OF INVESTIGATIVE DERMATOLOGY. - 0022-202X. ; 143:9, s. B10-B10
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 21. |
- Andersen, J. R., et al.
(författare)
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Small-x phenomenology - Summary of the 3rd Lund small-x workshop in 2004
- 2006
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 48:1, s. 53-105
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Forskningsöversikt (refereegranskat)abstract
- A third workshop on small-x physics, within the Small-x Collaboration, was held in Hamburg in May 2004 with the aim of overviewing recent theoretical progress in this area and summarizing the experimental status.
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| 22. |
- Anton, Christian, et al.
(författare)
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Research needs for incorporating the ecosystem service approach into EU biodiversity conservation policy
- 2010
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Ingår i: Biodiversity and Conservation. - : Springer Science and Business Media LLC. - 0960-3115 .- 1572-9710. ; 19:10, s. 2979-2994
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Tidskriftsartikel (refereegranskat)abstract
- Using a range of different methods including extensive reviews, workshops and an electronic conference, 70 key research recommendations and 12 priority research needs to integrate the ecosystem services approach into biodiversity conservation policy and funding were identified by a cross-disciplinary group of over 100 scientists and 50 stakeholders, including research funders and policy-makers. These recommendations focus on the ecological underpinning of ecosystem services, drivers that affect ecosystems and their services, biological traits and ecosystem services, the valuation of ecosystem services, spatial and temporal scales in ecosystem service assessment, indicators of ecosystem services, and habitat management, conservation policy and ecosystem services. The recommendations in this paper help steer the research agenda on ecosystem services into policy-relevant areas, agreed upon by funders, researchers and policy-makers. This research agenda will only succeed with increased collaboration between researchers across disciplines, thereby providing a challenge to the research community and research funders to work in new, interdisciplinary ways.
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| 23. |
- Apostolou, E, et al.
(författare)
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Progress and challenges in stem cell biology
- 2023
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Ingår i: Nature cell biology. - : Springer Science and Business Media LLC. - 1476-4679 .- 1465-7392. ; 25:2, s. 203-206
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Tidskriftsartikel (refereegranskat)
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| 24. |
- Berthomier, M., et al.
(författare)
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Alfven : magnetosphere-ionosphere connection explorers
- 2012
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Ingår i: Experimental astronomy. - Dordrecht : Springer. - 0922-6435 .- 1572-9508. ; 33:2-3, s. 445-489
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Tidskriftsartikel (refereegranskat)abstract
- The aurorae are dynamic, luminous displays that grace the night skies of Earth's high latitude regions. The solar wind emanating from the Sun is their ultimate energy source, but the chain of plasma physical processes leading to auroral displays is complex. The special conditions at the interface between the solar wind-driven magnetosphere and the ionospheric environment at the top of Earth's atmosphere play a central role. In this Auroral Acceleration Region (AAR) persistent electric fields directed along the magnetic field accelerate magnetospheric electrons to the high energies needed to excite luminosity when they hit the atmosphere. The "ideal magnetohydrodynamics" description of space plasmas which is useful in much of the magnetosphere cannot be used to understand the AAR. The AAR has been studied by a small number of single spacecraft missions which revealed an environment rich in wave-particle interactions, plasma turbulence, and nonlinear acceleration processes, acting on a variety of spatio-temporal scales. The pioneering 4-spacecraft Cluster magnetospheric research mission is now fortuitously visiting the AAR, but its particle instruments are too slow to allow resolve many of the key plasma physics phenomena. The Alfv,n concept is designed specifically to take the next step in studying the aurora, by making the crucial high-time resolution, multi-scale measurements in the AAR, needed to address the key science questions of auroral plasma physics. The new knowledge that the mission will produce will find application in studies of the Sun, the processes that accelerate the solar wind and that produce aurora on other planets.
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| 25. |
- Buitelaar, M. R., et al.
(författare)
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Pauli spin blockade in carbon nanotube double quantum dots
- 2008
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 77:24, s. 245439-
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Tidskriftsartikel (refereegranskat)abstract
- We report Pauli spin blockade in a carbon nanotube double quantum dot defined by tunnel barriers at the contacts and a structural defect in the nanotube. We observe a pronounced current suppression for negative source-drain bias voltages, which is investigated for both symmetric and asymmetric coupling of the quantum dots to the leads. The measured differential conductance agrees well with a theoretical model of a double quantum dot system in the spin-blockade regime, which allows us to estimate the occupation probabilities of the relevant singlet and triplet states. This work shows that effective spin-to-charge conversion in nanotube quantum dots is feasible and opens the possibility of single-spin readout in a material that is not limited by hyperfine interaction with nuclear spins.
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| 26. |
- Chow, LS, et al.
(författare)
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Exerkines in health, resilience and disease
- 2022
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Ingår i: Nature reviews. Endocrinology. - : Springer Science and Business Media LLC. - 1759-5037 .- 1759-5029. ; 18:5, s. 273-289
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Tidskriftsartikel (refereegranskat)
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| 27. |
- Cohen, Lois K, et al.
(författare)
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Dentistry's future.
- 2018
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Ingår i: Journal of the American Dental Association. - : Elsevier BV. - 1943-4723 .- 0002-8177. ; 149:9, s. 752-753
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 28. |
- Forsyth, C., et al.
(författare)
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In situ spatiotemporal measurements of the detailed azimuthal substructure of the substorm current wedge
- 2014
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Ingår i: Journal of Geophysical Research: Space Physics. - 2169-9380. ; 119:2, s. 927-946
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Tidskriftsartikel (refereegranskat)abstract
- The substorm current wedge (SCW) is a fundamental component of geomagnetic substorms. Models tend to describe the SCW as a simple line current flowing into the ionosphere toward dawn and out of the ionosphere toward dusk, linked by a westward electrojet. We use multispacecraft observations from perigee passes of the Cluster 1 and 4 spacecraft during a substorm on 15 January 2010, in conjunction with ground-based observations, to examine the spatial structuring and temporal variability of the SCW. At this time, the spacecraft traveled east-west azimuthally above the auroral region. We show that the SCW has significant azimuthal substructure on scales of 100km at altitudes of 4000-7000km. We identify 26 individual current sheets in the Cluster 4 data and 34 individual current sheets in the Cluster 1 data, with Cluster 1 passing through the SCW 120-240s after Cluster 4 at 1300-2000km higher altitude. Both spacecraft observed large-scale regions of net upward and downward field-aligned current, consistent with the large-scale characteristics of the SCW, although sheets of oppositely directed currents were observed within both regions. We show that the majority of these current sheets were closely aligned to a north-south direction, in contrast to the expected east-west orientation of the preonset aurora. Comparing our results with observations of the field-aligned current associated with bursty bulk flows (BBFs), we conclude that significant questions remain for the explanation of SCW structuring by BBF-driven wedgelets. Our results therefore represent constraints on future modeling and theoretical frameworks on the generation of the SCW.
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| 29. |
- Karampelias, C, et al.
(författare)
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MNK2 deficiency potentiates β-cell regeneration via translational regulation
- 2022
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Ingår i: Nature chemical biology. - : Springer Science and Business Media LLC. - 1552-4469 .- 1552-4450. ; 18:9, s. 942-
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Tidskriftsartikel (refereegranskat)abstract
- Regenerating pancreatic β-cells is a potential curative approach for diabetes. We previously identified the small molecule CID661578 as a potent inducer of β-cell regeneration, but its target and mechanism of action have remained unknown. We now screened 257 million yeast clones and determined that CID661578 targets MAP kinase-interacting serine/threonine kinase 2 (MNK2), an interaction we genetically validated in vivo. CID661578 increased β-cell neogenesis from ductal cells in zebrafish, neonatal pig islet aggregates and human pancreatic ductal organoids. Mechanistically, we found that CID661578 boosts protein synthesis and regeneration by blocking MNK2 from binding eIF4G in the translation initiation complex at the mRNA cap. Unexpectedly, this blocking activity augmented eIF4E phosphorylation depending on MNK1 and bolstered the interaction between eIF4E and eIF4G, which is necessary for both hypertranslation and β-cell regeneration. Taken together, our findings demonstrate a targetable role of MNK2-controlled translation in β-cell regeneration, a role that warrants further investigation in diabetes.
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| 30. |
- Kettle, B., et al.
(författare)
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Single-Shot Multi-keV X-Ray Absorption Spectroscopy Using an Ultrashort Laser-Wakefield Accelerator Source
- 2019
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Ingår i: Physical Review Letters. - 0031-9007. ; 123:25
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Tidskriftsartikel (refereegranskat)abstract
- Single-shot absorption measurements have been performed using the multi-keV x rays generated by a laser-wakefield accelerator. A 200 TW laser was used to drive a laser-wakefield accelerator in a mode which produced broadband electron beams with a maximum energy above 1 GeV and a broad divergence of ≈15 mrad FWHM. Betatron oscillations of these electrons generated 1.2±0.2×106 photons/eV in the 5 keV region, with a signal-to-noise ratio of approximately 300 1. This was sufficient to allow high-resolution x-ray absorption near-edge structure measurements at the K edge of a titanium sample in a single shot. We demonstrate that this source is capable of single-shot, simultaneous measurements of both the electron and ion distributions in matter heated to eV temperatures by comparison with density functional theory simulations. The unique combination of a high-flux, large bandwidth, few femtosecond duration x-ray pulse synchronized to a high-power laser will enable key advances in the study of ultrafast energetic processes such as electron-ion equilibration.
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| 31. |
- Kloppenburg, Margreet, et al.
(författare)
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Research in hand osteoarthritis: time for reappraisal and demand for new strategies. An opinion paper
- 2007
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 66:9, s. 1157-1161
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Osteoarthritis of the hands is a prevalent musculoskeletal disease with a considerable effect on patients' lives, but knowledge and research results in the field of hand osteoarthritis are limited. Therefore, the Disease Characteristics in Hand OA (DICHOA) initiative was founded in early 2005 with the aim of addressing key issues and facilitating research into hand osteoarthritis. OBJECTIVE: To review and discuss current knowledge on hand osteoarthritis with regard to aetiopathogenesis, diagnostic criteria, biomarkers and clinical outcome measures. METHODS: Recommendations were made based on a literature review. RESULTS: Outcomes of hand osteoarthritis should be explored, including patient perspective on the separate components of disease activity, damage and functioning. All imaging techniques should be cross-validated for hand osteoarthritis with clinical status, including disease activity, function and performance, biomarkers and long-term outcome. New imaging modalities are available and need scoring systems and validation. The role of biomarkers in hand osteoarthritis has to be defined. CONCLUSION: Future research in hand osteoarthritis is warranted.
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| 36. |
- Sjölin, Gabriel, 1979-, et al.
(författare)
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Long term outcome after toxic nodular goitre
- 2022
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Ingår i: Thyroid Research. - : Springer Science and Business Media LLC. - 1756-6614. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The purpose of treating toxic nodular goitre (TNG) is to reverse hyperthyroidism, prevent recurrent disease, relieve symptoms and preserve thyroid function. Treatment efficacies and long-term outcomes of antithyroid drugs (ATD), radioactive iodine (RAI) or surgery vary in the literature. Symptoms often persist for a long time following euthyroidism, and previous studies have demonstrated long-term cognitive and quality of life (QoL) impairments. We report the outcome of treatment, rate of cure (euthyroidism and hypothyroidism), and QoL in an unselected TNG cohort. Methods: TNG patients (n = 638) de novo diagnosed between 2003-2005 were invited to engage in a 6-10-year follow-up study. 237 patients responded to questionnaires about therapies, demographics, comorbidities, and quality of life (ThyPRO). Patients received ATD, RAI, or surgery according clinical guidelines. Results: The fraction of patients cured with one RAI treatment was 89%, and 93% in patients treated with surgery. The rate of levothyroxine supplementation for RAI and surgery, at the end of the study period, was 58% respectively 64%. Approximately 5% of the patients needed three or more RAI treatments to be cured. The patients had worse thyroid-related QoL scores, in a broad spectrum, than the general population. Conclusion: One advantage of treating TNG with RAI over surgery might be lost due to the seemingly similar incidence of hypothyroidism. The need for up to five treatments is rarely described and indicates that the treatment of TNG can be more complex than expected. This circumstance and the long-term QoL impairments are reminders of the chronic nature of hyperthyroidism from TNG.
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| 37. |
- Wanrooij, Paulina H., et al.
(författare)
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Elimination of rNMPs from mitochondrial DNA has no effect on its stability
- 2020
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 117:25, s. 14306-14313
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Tidskriftsartikel (refereegranskat)abstract
- Ribonucleotides (rNMPs) incorporated in the nuclear genome are a well-established threat to genome stability and can result in DNA strand breaks when not removed in a timely manner. However, the presence of a certain level of rNMPs is tolerated in mitochondrial DNA (mtDNA) although aberrant mtDNA rNMP content has been identified in disease models. We investigated the effect of incorporated rNMPs on mtDNA stability over the mouse life span and found that the mtDNA rNMP content increased during early life. The rNMP content of mtDNA varied greatly across different tissues and was defined by the rNTP/dNTP ratio of the tissue. Accordingly, mtDNA rNMPs were nearly absent in SAMHD1(-/-) mice that have increased dNTP pools. The near absence of rNMPs did not, however, appreciably affect mtDNA copy number or the levels of mtDNA molecules with deletions or strand breaks in aged animals near the end of their life span. The physiological rNMP load therefore does not contribute to the progressive loss of mtDNA quality that occurs as mice age.
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| 38. |
- Watt, F. E., et al.
(författare)
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Towards prevention of post-traumatic osteoarthritis : report from an international expert working group on considerations for the design and conduct of interventional studies following acute knee injury
- 2019
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 27:1, s. 23-33
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Tidskriftsartikel (refereegranskat)abstract
- Objective: There are few guidelines for clinical trials of interventions for prevention of post-traumatic osteoarthritis (PTOA), reflecting challenges in this area. An international multi-disciplinary expert group including patients was convened to generate points to consider for the design and conduct of interventional studies following acute knee injury. Design: An evidence review on acute knee injury interventional studies to prevent PTOA was presented to the group, alongside overviews of challenges in this area, including potential targets, biomarkers and imaging. Working groups considered pre-identified key areas: eligibility criteria and outcomes, biomarkers, injury definition and intervention timing including multi-modality interventions. Consensus agreement within the group on points to consider was generated and is reported here after iterative review by all contributors. Results: The evidence review identified 37 studies. Study duration and outcomes varied widely and 70% examined surgical interventions. Considerations were grouped into three areas: justification of inclusion criteria including the classification of injury and participant age (as people over 35 may have pre-existing OA); careful consideration in the selection and timing of outcomes or biomarkers; definition of the intervention(s)/comparator(s) and the appropriate time-window for intervention (considerations may be particular to intervention type). Areas for further research included demonstrating the utility of patient-reported outcomes, biomarkers and imaging outcomes from ancillary/cohort studies in this area, and development of surrogate clinical trial endpoints that shorten the duration of clinical trials and are acceptable to regulatory agencies. Conclusions: These considerations represent the first international consensus on the conduct of interventional studies following acute knee joint trauma.
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