| 1. |
- 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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| 2. |
- Kueppers, Michael, et al.
(författare)
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Triple F-a comet nucleus sample return mission
- 2009
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Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 23:3, s. 809-847
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Tidskriftsartikel (refereegranskat)abstract
- The Triple F (Fresh From the Fridge) mission, a Comet Nucleus Sample Return, has been proposed to ESA's Cosmic Vision program. A sample return from a comet enables us to reach the ultimate goal of cometary research. Since comets are the least processed bodies in the solar system, the proposal goes far beyond cometary science topics (like the explanation of cometary activity) and delivers invaluable information about the formation of the solar system and the interstellar molecular cloud from which it formed. The proposed mission would extract three sample cores of the upper 50 cm from three locations on a cometary nucleus and return them cooled to Earth for analysis in the laboratory. The simple mission concept with a touch-and-go sampling by a single spacecraft was proposed as an M-class mission in collaboration with the Russian space agency ROSCOSMOS.
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| 3. |
- Lønborg, C., et al.
(författare)
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A global database of dissolved organic matter (DOM) concentration measurements in coastal waters (CoastDOM v1)
- 2024
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Ingår i: Earth System Science Data. - : Copernicus Publications. - 1866-3508 .- 1866-3516. ; 16:2, s. 1107-1119
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Tidskriftsartikel (refereegranskat)abstract
- Measurements of dissolved organic carbon (DOC), nitrogen (DON), and phosphorus (DOP) concentrations are used to characterize the dissolved organic matter (DOM) pool and are important components ofbiogeochemical cycling in the coastal ocean. Here, we present the first edition of a global database (CoastDOMv1; available at https://doi.org/10.1594/PANGAEA.964012, Lønborg et al., 2023) compiling previously published and unpublished measurements of DOC, DON, and DOP in coastal waters. These data are complementedby hydrographic data such as temperature and salinity and, to the extent possible, other biogeochemical variables(e.g. chlorophyll a, inorganic nutrients) and the inorganic carbon system (e.g. dissolved inorganic carbon andtotal alkalinity). Overall, CoastDOM v1 includes observations of concentrations from all continents. However,most data were collected in the Northern Hemisphere, with a clear gap in DOM measurements from the SouthernHemisphere. The data included were collected from 1978 to 2022 and consist of 62 338 data points for DOC,20 356 for DON, and 13 533 for DOP. The number of measurements decreases progressively in the sequenceDOC > DON > DOP, reflecting both differences in the maturity of the analytical methods and the greater focuson carbon cycling by the aquatic science community. The global database shows that the average DOC concentration in coastal waters (average ± standard deviation (SD): 182±314 µmolC L−1; median: 103 µmolC L−1) is13-fold higher than the average coastal DON concentration (13.6 ± 30.4 µmol N L−1; median: 8.0 µmol N L−1),which is itself 39-fold higher than the average coastal DOP concentration (0.34 ± 1.11 µmol P L−1; median:0.18 µmol P L−1). This dataset will be useful for identifying global spatial and temporal patterns in DOM and willhelp facilitate the reuse of DOC, DON, and DOP data in studies aimed at better characterizing local biogeochemical processes; closing nutrient budgets; estimating carbon, nitrogen, and phosphorous pools; and establishing abaseline for modelling future changes in coastal waters.
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| 4. |
- Swat, M. J., et al.
(författare)
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Pharmacometrics Markup Language (PharmML) : Opening New Perspectives for Model Exchange in Drug Development
- 2015
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Ingår i: CPT. - : American Society for Clinical Pharmacology & Therapeutics. - 2163-8306. ; 4:6, s. 316-319
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Tidskriftsartikel (refereegranskat)abstract
- The lack of a common exchange format for mathematical models in pharmacometrics has been a long-standing problem. Such a format has the potential to increase productivity and analysis quality, simplify the handling of complex workflows, ensure reproducibility of research, and facilitate the reuse of existing model resources. Pharmacometrics Markup Language (PharmML), currently under development by the Drug Disease Model Resources (DDMoRe) consortium, is intended to become an exchange standard in pharmacometrics by providing means to encode models, trial designs, and modeling steps.
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| 5. |
- Contessotto, P., et al.
(författare)
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Reproducing extracellular matrix adverse remodelling of non-ST myocardial infarction in a large animal model
- 2023
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The rising incidence of non-ST-segment elevation myocardial infarction (NSTEMI) and associated long-term high mortality constitutes an urgent clinical issue. Unfortunately, the study of possible interventions to treat this pathology lacks a reproducible pre-clinical model. Indeed, currently adopted small and large animal models of MI mimic only full-thickness, ST-segment-elevation (STEMI) infarcts, and hence cater only for an investigation into therapeutics and interventions directed at this subset of MI. Thus, we develop an ovine model of NSTEMI by ligating the myocardial muscle at precise intervals parallel to the left anterior descending coronary artery. Upon histological and functional investigation to validate the proposed model and comparison with STEMI full ligation model, RNA-seq and proteomics show the distinctive features of post-NSTEMI tissue remodelling. Transcriptome and proteome-derived pathway analyses at acute (7 days) and late (28 days) post-NSTEMI pinpoint specific alterations in cardiac post-ischaemic extracellular matrix. Together with the rise of well-known markers of inflammation and fibrosis, NSTEMI ischaemic regions show distinctive patterns of complex galactosylated and sialylated N-glycans in cellular membranes and extracellular matrix. Identifying such changes in molecular moieties accessible to infusible and intra-myocardial injectable drugs sheds light on developing targeted pharmacological solutions to contrast adverse fibrotic remodelling. The study of the pathophysiology and possible interventions for non-ST-segment elevation myocardial infarction is hindered by the lack of a reproducible pre-clinical model. Here, authors develop an ovine model to reproduce post-ischemic remodeling in non-ST myocardial infarction and reveal distinct complex sugar moieties in cellular membranes and extracellular matrix patterns in infarcted tissue.
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| 6. |
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| 7. |
- Spelat, R., et al.
(författare)
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Metabolic reprogramming and membrane glycan remodeling as potential drivers of zebrafish heart regeneration
- 2022
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- The ability of the zebrafish heart to regenerate following injury makes it a valuable model to deduce why this capability in mammals is limited to early neonatal stages. Although metabolic reprogramming and glycosylation remodeling have emerged as key aspects in many biological processes, how they may trigger a cardiac regenerative response in zebrafish is still a crucial question. Here, by using an up-to-date panel of transcriptomic, proteomic and glycomic approaches, we identify a metabolic switch from mitochondrial oxidative phosphorylation to glycolysis associated with membrane glycosylation remodeling during heart regeneration. Importantly, we establish the N- and O-linked glycan structural repertoire of the regenerating zebrafish heart, and link alterations in both sialylation and high mannose structures across the phases of regeneration. Our results show that metabolic reprogramming and glycan structural remodeling are potential drivers of tissue regeneration after cardiac injury, providing the biological rationale to develop novel therapeutics to elicit heart regeneration in mammals.
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| 8. |
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| 9. |
- Vanhatalo, A., et al.
(författare)
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The mechanistic bases of the power–time relationship: muscle metabolic responses and relationships to muscle fibre type
- 2016
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Ingår i: Journal of Physiology. - 0022-3751. ; 594:15, s. 4407-4423
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Tidskriftsartikel (refereegranskat)abstract
- Key points: The power-asymptote (critical power; CP) of the hyperbolic power–time relationship for high-intensity exercise defines a threshold between steady-state and non-steady-state exercise intensities and the curvature constant (W′) indicates a fixed capacity for work >CP that is related to a loss of muscular efficiency. The present study reports novel evidence on the muscle metabolic underpinnings of CP and W′ during whole-body exercise and their relationships to muscle fibre type. We show that the W′ is not correlated with muscle fibre type distribution and that it represents an elevated energy contribution from both oxidative and glycolytic/glycogenolytic metabolism. We show that there is a positive correlation between CP and highly oxidative type I muscle fibres and that muscle metabolic steady-state is attainable CP. Our findings indicate a mechanistic link between the bioenergetic characteristics of muscle fibre types and the power–time relationship for high-intensity exercise. Abstract: We hypothesized that: (1) the critical power (CP) will represent a boundary separating steady-state from non-steady-state muscle metabolic responses during whole-body exercise and (2) that the CP and the curvature constant (W′) of the power–time relationship for high-intensity exercise will be correlated with type I and type IIx muscle fibre distributions, respectively. Four men and four women performed a 3min all-out cycling test for the estimation of CP and constant work rate (CWR) tests slightly >CP until exhaustion (Tlim), slightly CP Tlim isotime to test the first hypothesis. Eleven men performed 3min all-out tests and donated muscle biopsies to test the second hypothesis. Below CP, muscle [PCr] [42.6±7.1vs. 49.4±6.9mmol(kgd.w.)−1], [La−] [34.8±12.6vs. 35.5±13.2mmol(kgd.w.)−1] and pH (7.11±0.08 vs. 7.10±0.11) remained stable between ∼12 and 24min (P>0.05 for all), whereas these variables changed with time >CP such that they were greater [[La−] 95.6±14.1mmol(kgd.w.)−1] and lower [[PCr] 24.2±3.9mmol(kgd.w.)−1; pH 6.84±0.06] (P<0.05) at Tlim (740±186s) than during the
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