| 1. |
- Lyons, PA, et al.
(författare)
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Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 5120-
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA.
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| 2. |
- Sator, Lea, et al.
(författare)
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Overdiagnosis of COPD in Subjects With Unobstructed Spirometry A BOLD Analysis
- 2019
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Ingår i: Chest. - : Elsevier BV. - 0012-3692 .- 1931-3543. ; 156:2, s. 277-288
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There are several reports on underdiagnosis of COPD, while little is known about COPD overdiagnosis and overtreatment. We describe the overdiagnosis and the prevalence of spirometrically defined false positive COPD, as well as their relationship with overtreatment across 23 population samples in 20 countries participating in the BOLD Study between 2003 and 2012.METHODS: A false positive diagnosis of COPD was considered when participants reported a doctor's diagnosis of COPD, but postbronchodilator spirometry was unobstructed (FEV1/FVC > LLN). Additional analyses were performed using the fixed ratio criterion (FEV1/FVC < 0.7).RESULTS: Among 16,177 participants, 919 (5.7%) reported a previous medical diagnosis of COPD. Postbronchodilator spirometry was unobstructed in 569 subjects (61.9%): false positive COPD. A similar rate of overdiagnosis was seen when using the fixed ratio criterion (55.3%). In a subgroup analysis excluding participants who reported a diagnosis of "chronic bronchitis" or "emphysema" (n = 220), 37.7% had no airflow limitation. The site-specific prevalence of false positive COPD varied greatly, from 1.9% in low- to middle-income countries to 4.9% in high-income countries. In multivariate analysis, overdiagnosis was more common among women, and was associated with higher education; former and current smoking; the presence of wheeze, cough, and phlegm; and concomitant medical diagnosis of asthma or heart disease. Among the subjects with false positive COPD, 45.7% reported current use of respiratory medication. Excluding patients with reported asthma, 34.4% of those with normal spirometry still used a respiratory medication.CONCLUSIONS: False positive COPD is frequent. This might expose nonobstructed subjects to possible adverse effects of respiratory medication.
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| 3. |
- Dobsicek Trefna, Hana, 1979, et al.
(författare)
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Quality assurance guidelines for interstitial hyperthermia
- 2019
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Ingår i: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 36:1, s. 277-294
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Tidskriftsartikel (refereegranskat)abstract
- Quality assurance (QA) guidelines are essential to provide uniform execution of clinical hyperthermia treatments and trials. This document outlines the clinical and technical consequences of the specific properties of interstitial heat delivery and specifies recommendations for hyperthermia administration with interstitial techniques. Interstitial hyperthermia aims at tumor temperatures in the 40–44 °C range as an adjunct to radiation or chemotherapy. The clinical part of this document imparts specific clinical experience of interstitial heat delivery to various tumor sites as well as recommended interstitial hyperthermia workflow and procedures. The second part describes technical requirements for quality assurance of current interstitial heating equipment including electromagnetic (radiative and capacitive) and ultrasound heating techniques. Detailed instructions are provided on characterization and documentation of the performance of interstitial hyperthermia applicators to achieve reproducible hyperthermia treatments of uniform high quality. Output power and consequent temperature rise are the key parameters for characterization of applicator performance in these QA guidelines. These characteristics determine the specific maximum tumor size and depth that can be heated adequately. The guidelines were developed by the ESHO Technical Committee with participation of senior STM members and members of the Atzelsberg Circle.
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| 4. |
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| 5. |
- Dobsicek Trefna, Hana, 1979, et al.
(författare)
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Quality assurance guidelines for superficial hyperthermia clinical trials: II. Technical requirements for heating devices
- 2017
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Ingår i: Strahlentherapie und Onkologie. - : Springer Science and Business Media LLC. - 1439-099X .- 0179-7158. ; 193:5, s. 351-366
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Forskningsöversikt (refereegranskat)abstract
- Quality assurance (QA) guidelines are essential to provide uniform execution of clinical trials with uniform quality hyperthermia treatments. This document outlines the requirements for appropriate QA of all current superficial heating equipment including electromagnetic (radiative and capacitive), ultrasound, and infrared heating techniques. Detailed instructions are provided how to characterize and document the performance of these hyperthermia applicators in order to apply reproducible hyperthermia treatments of uniform high quality. Earlier documents used specific absorption rate (SAR) to define and characterize applicator performance. In these QA guidelines, temperature rise is the leading parameter for characterization of applicator performance. The intention of this approach is that characterization can be achieved with affordable equipment and easy-to-implement procedures. These characteristics are essential to establish for each individual applicator the specific maximum size and depth of tumors that can be heated adequately. The guidelines in this document are supplemented with a second set of guidelines focusing on the clinical application. Both sets of guidelines were developed by the European Society for Hyperthermic Oncology (ESHO) Technical Committee with participation of senior Society of Thermal Medicine (STM) members and members of the Atzelsberg Circle.
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| 6. |
- Dobsicek Trefna, Hana, 1979, et al.
(författare)
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Quality assurance guidelines for superficial hyperthermia clinical trials: I. Clinical requirements
- 2017
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Ingår i: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 33:4, s. 471-482
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Tidskriftsartikel (refereegranskat)abstract
- Quality assurance guidelines are essential to provide uniform execution of clinical trials and treatment in the application of hyperthermia. This document provides definitions for a good hyperthermia treatment and identifies the clinical conditions where a certain hyperthermia system can or cannot adequately heat the tumour volume. It also provides brief description of the characteristics and performance of the current electromagnetic (radiative and capacitive), ultrasound and infra-red heating techniques. This information helps to select the appropriate heating technique for the specific tumour location and size, and appropriate settings of the water bolus and thermometry. Finally, requirements of staff training and documentation are provided. The guidelines in this document focus on the clinical application and are complemented with a second, more technical quality assurance document providing instructions and procedure to determine essential parameters that describe heating properties of the applicator for superficial hyperthermia. Both sets of guidelines were developed by the ESHO Technical Committee with participation of senior STM members and members of the Atzelsberg Circle.
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| 7. |
- Winkler, M., et al.
(författare)
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The rich sides of mountain summits - a pan-European view on aspect preferences of alpine plants
- 2016
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Ingår i: Journal of Biogeography. - : Wiley. - 0305-0270. ; 43:11, s. 2261-2273
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Tidskriftsartikel (refereegranskat)abstract
- Aim In the alpine life zone, plant diversity is strongly determined by local topography and microclimate. We assessed the extent to which aspect and its relatedness to temperature affect plant species diversity, and the colonization and disappearance of species on alpine summits on a pan-European scale. Methods Vascular plant species and their percentage cover were recorded in permanent plots in each cardinal direction on 123 summits in 32 regions across Europe. For a subset from 17 regions, resurvey data and 6-year soil temperature series were available. Differences in temperature sum and Shannon index as well as species richness, colonization and disappearance of species among cardinal directions were analysed using linear mixed-effects and generalised mixed-effects models, respectively. Results Temperature sums were higher in east-and south-facing aspects than in the north-facing ones, while the west-facing ones were intermediate; differences were smallest in northern Europe. The patterns of temperature sums among aspects were consistent among years. In temperate regions, thermal differences were reflected by plant diversity, whereas this relationship was weaker or absent on Mediterranean and boreal mountains. Colonization of species was positively related to temperature on Mediterranean and temperate mountains, whereas disappearance of species was not related to temperature. Main conclusions Thermal differences caused by solar radiation determine plant species diversity on temperate mountains. Advantages for plants on eastern slopes may result from the combined effects of a longer diurnal period of radiation due to convection cloud effects in the afternoon and the sheltered position against the prevailing westerly winds. In northern Europe, long summer days and low sun angles can even out differences among aspects. On Mediterranean summits, summer drought may limit species numbers on the warmer slopes. Warmer aspects support a higher number of colonization events. Hence, aspect can be a principal determinant of the pace of climate-induced migration processes.
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