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| 2. |
- van Bragt, JJMH, et al.
(författare)
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Characteristics and treatment regimens across ERS SHARP severe asthma registries
- 2020
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:1
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals.This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases.Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m−2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day−1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day−1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively.The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries.
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| 3. |
- Michelsen, B., et al.
(författare)
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Impact of discordance between patient's and evaluator's global assessment on treatment outcomes in 14 868 patients with spondyloarthritis
- 2020
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 59:9, s. 2455-2461
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To assess the impact of 'patient's minus evaluator's global assessment of disease activity' (Delta PEG) at treatment initiation on retention and remission rates of TNF inhibitors (TNFi) in psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) patients across Europe. Methods. Real-life data from PsA and axSpA patients starting their first TNFi from 11 countries in the European Spondyloarthritis Research Collaboration Network were pooled. Retention rates were compared by Kaplan-Meier analyses with log-rank test and by Cox regression, and remission rates by chi(2) test and by logistic regression across quartiles of baseline Delta PEG, separately in female and male PsA and axSpA patients. Results. We included 14 868 spondyloarthritis (5855 PsA, 9013 axSpA) patients. Baseline Delta PEG was negatively associated with 6/12/24-months' TNFi retention rates in female and male PsA and axSpA patients (P < 0.001), with 6/12/24-months' BASDAI < 2 (P <= 0.002) and ASDAS < 1.3 (P <= 0.005) in axSpA patients, and with DAS28CRP(4)<2.6 (P <= 0.04) and DAPSA28 <= 4 (P <= 0.01), but not DAS28CRP(3)<2.6 (P >= 0.13) in PsA patients, with few exceptions on remission rates. Retention and remission rates were overall lower in female than male patients. Conclusion. High baseline patient's compared with evaluator's global assessment was associated with lower 6/12/24-months' remission as well as retention rates of first TNFi in both PsA and axSpA patients. These results highlight the importance of discordance between patient's and evaluator's perspective on disease outcomes.
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| 4. |
- Soares, M., et al.
(författare)
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Particles in exhaled air (PExA): non-invasive phenotyping of small airways disease in adult asthma
- 2018
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Ingår i: Journal of Breath Research. - : IOP Publishing. - 1752-7155 .- 1752-7163. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Asthma is often characterised by inflammation, damage and dysfunction of the small airways, but no standardised biomarkers are available. Objectives: Using a novel approach-particles in exhaled air (PExA)-we sought to (a) sample and analyse abundant protein biomarkers: surfactant protein A (SPA) and albumin in adult asthmatic and healthy patients and (b) relate protein concentrations with physiological markers using phenotyping. Methods: 83 adult asthmatics and 21 healthy volunteers were recruited from a discovery cohort in Leicester, UK, and 32 adult asthmatics as replication cohort from Sweden. Markers of airways closure/small airways dysfunction were evaluated using forced vital capacity, impulse oscillometry and multiple breath washout. SPA/albumin from PEx (PExA sample) were analysed using ELISA and corrected for acquired particle mass. Topological data analysis (TDA) was applied to small airway physiology and PExA protein data to identify phenotypes. Results: PExA manoeuvres were feasible, including severe asthmatic subjects. TDA identified a clinically important phenotype of asthmatic patients with multiple physiological markers of peripheral airway dysfunction, and significantly lower levels of both SPA and albumin. Conclusion: We report that the PExA method is feasible across the spectrum of asthma severity and could be used to identify small airway disease phenotypes.
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| 5. |
- Strandberg, Bo, 1960, et al.
(författare)
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An improved method for determining dermal exposure to polycyclic aromatic hydrocarbons
- 2018
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 198, s. 274-280
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Tidskriftsartikel (refereegranskat)abstract
- Many workers are occupationally exposed to polycyclic aromatic hydrocarbons (PAHs), which may cause various health problems, and some PAHs are known or suspected carcinogens. PAH exposure is primarily monitored by air sampling, but contamination may also occur through dermal exposure. PAHs adsorbed to the skin can be sampled by tape-stripping, but subsequent extraction of sampling tapes in organic solvent also releases diverse co-eluting substances that are difficult to remove before analysis of the PAHs by gas chromatography/mass spectrometry (GC/MS). The objective of this study was to optimise a procedure for analytical clean-up after extraction of 32 PAHs from tape-strips, by dialysis in organic solvent using semipermeable membranes. With triplicate subsamples, the developed method yields acceptable precision and repeatability for both the 32 PAHs, across the concentration range 10-160 ng per sample, and for a certified reference material (urban dust). The optimized clean-up procedure and GC/MS methodology was used to assess PAHs on skin from the lower part of the ventral side of the wrist and just below the collar bone of three firefighters and seven controls (office workers). Several gaseous and particle-bound PAHs were detected in all samples, including controls. Thus, the optimized procedure using semipermeable membranes for clean-up of tape-strip extracts can be used to assess the dermal exposure of both occupational and general populations to multiple PAHs. The results also show that both gaseous and particle-bound PAHs, including alkylated species, may be present on skin.
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| 6. |
- Strandberg, Bo, 1960, et al.
(författare)
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Evaluation of polyurethane foam passive air sampler (PUF) as a tool for occupational PAH measurements
- 2018
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 190, s. 35-42
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Tidskriftsartikel (refereegranskat)abstract
- Routine monitoring of workplace exposure to polycyclic aromatic hydrocarbons (PAHs) is performed mainly via active sampling. However, active samplers have several drawbacks and, in some cases, may even be unusable. Polyurethane foam (PUF) as personal passive air samplers constitute good alternatives for PAH monitoring in occupational air (8 h). However, PUFs must be further tested to reliably yield detectable levels of PAHs in short exposure times (1–3 h) and under extreme occupational conditions. Therefore, we compared the personal exposure monitoring performance of a passive PUF sampler with that of an active air sampler and determined the corresponding uptake rates (Rs). These rates were then used to estimate the occupational exposure of firefighters and police forensic specialists to 32 PAHs. The work environments studied were heavily contaminated by PAHs with (for example) benzo(a)pyrene ranging from 0.2 to 56 ng m−3, as measured via active sampling. We show that, even after short exposure times, PUF can reliably accumulate both gaseous and particle-bound PAHs. The Rs-values are almost independent of variables such as the concentration and the wind speed. Therefore, by using the Rs-values (2.0–20 m3 day−1), the air concentrations can be estimated within a factor of two for gaseous PAHs and a factor of 10 for particulate PAHs. With very short sampling times (1 h), our method can serve as a (i) simple and user-friendly semi-quantitative screening tool for estimating and tracking point sources of PAH in micro-environments and (ii) complement to the traditional active pumping methods. © 2017 The Authors
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| 7. |
- Tsagarakis, Konstantinos P., et al.
(författare)
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A review of the legal framework in shallow geothermal energy in selected European countries : Need for guidelines
- 2020
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Ingår i: Renewable Energy. - : Elsevier BV. - 0960-1481. ; 147:Part 2, s. 2556-2571
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Tidskriftsartikel (refereegranskat)abstract
- Over the past years, the installations of Shallow Geothermal Energy (SGE) systems are increasing throughout Europe, and it is indicating that a specific and detailed legal framework is necessary. Towards this direction, this paper consists of an overview of legislation issues on SGE at European level, based on concise reviews from fourteen countries, i.e., Croatia, Cyprus, France, Greece, Italy, Latvia, Lithuania, Poland, Portugal, Serbia, Slovenia, Spain, Sweden, and Turkey. Said reviews discuss key national legislation as well as experts’ experience in the procedure of SGE integration. Legal and technical issues are also critically discussed for all involved countries, both individually and collectively. Findings show that high diversity exists on legislation provisions as well as on regulations, standards, and institutional support amongst European countries. The latter acts as an effective barrier for the further development of the SGE market; therefore indicating the need for a common approach. Increase of awareness, need for standardization, improvement of legal framework, and administration procedures and permitting, are essential steps in moving forward and supporting the effectiveness of design, construction, maintenance, and operation of SGE systems.
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| 8. |
- Öz, Robin, 1992, et al.
(författare)
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Dynamics of Ku and bacterial non-homologous end-joining characterized using single DNA molecule analysis
- 2021
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 49:5, s. 2629-2641
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Tidskriftsartikel (refereegranskat)abstract
- We use single-molecule techniques to characterize the dynamics of prokaryotic DNA repair by non-homologous end-joining (NHEJ), a system comprised only of the dimeric Ku and Ligase D (LigD). The Ku homodimer alone forms a ∼2 s synapsis between blunt DNA ends that is increased to ∼18 s upon addition of LigD, in a manner dependent on the C-terminal arms of Ku. The synapsis lifetime increases drastically for 4 nt complementary DNA overhangs, independently of the C-terminal arms of Ku. These observations are in contrast to human Ku, which is unable to bridge either of the two DNA substrates. We also demonstrate that bacterial Ku binds the DNA ends in a cooperative manner for synapsis initiation and remains stably bound at DNA junctions for several hours after ligation is completed, indicating that a system for removal of the proteins is active in vivo. Together these experiments shed light on the dynamics of bacterial NHEJ in DNA end recognition and processing. We speculate on the evolutionary similarities between bacterial and eukaryotic NHEJ and discuss how an increased understanding of bacterial NHEJ can open the door for future antibiotic therapies targeting this mechanism.
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