| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- 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.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Morales, D. R., et al.
(författare)
-
Characteristics and outcomes of COVID-19 patients with and without asthma from the United States, South Korea, and Europe
- 2023
-
Ingår i: Journal of Asthma. - : Informa UK Limited. - 0277-0903 .- 1532-4303. ; 60:1, s. 76-86
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Large international comparisons describing the clinical characteristics of patients with COVID-19 are limited. The aim of the study was to perform a large-scale descriptive characterization of COVID-19 patients with asthma. Methods: We included nine databases contributing data from January to June 2020 from the US, South Korea (KR), Spain, UK and the Netherlands. We defined two cohorts of COVID-19 patients ('diagnosed' and 'hospitalized') based on COVID-19 disease codes. We followed patients from COVID-19 index date to 30 days or death. We performed descriptive analysis and reported the frequency of characteristics and outcomes in people with asthma defined by codes and prescriptions. Results: The diagnosed and hospitalized cohorts contained 666,933 and 159,552 COVID-19 patients respectively. Exacerbation in people with asthma was recorded in 1.6-8.6% of patients at presentation. Asthma prevalence ranged from 6.2% (95% CI 5.7-6.8) to 18.5% (95% CI 18.2-18.8) in the diagnosed cohort and 5.2% (95% CI 4.0-6.8) to 20.5% (95% CI 18.6-22.6) in the hospitalized cohort. Asthma patients with COVID-19 had high prevalence of comorbidity including hypertension, heart disease, diabetes and obesity. Mortality ranged from 2.1% (95% CI 1.8-2.4) to 16.9% (95% CI 13.8-20.5) and similar or lower compared to COVID-19 patients without asthma. Acute respiratory distress syndrome occurred in 15-30% of hospitalized COVID-19 asthma patients. Conclusion: The prevalence of asthma among COVID-19 patients varies internationally. Asthma patients with COVID-19 have high comorbidity. The prevalence of asthma exacerbation at presentation was low. Whilst mortality was similar among COVID-19 patients with and without asthma, this could be confounded by differences in clinical characteristics. Further research could help identify high-risk asthma patients. KEY MESSAGES Asthma prevalence in COVID-19 patients varied internationally (5.2-20.5%).The prevalence of asthma exacerbation at presentation with COVID-19 in diagnosed and hospitalized patients was low.Comorbidities were common in COVID-19 patients with asthma. Supplemental data for this article is available online at https://doi.org/10.1080/02770903.2021.2025392 .
|
|
| 8. |
- Sena, AG, et al.
(författare)
-
FIRST LINE TREATMENT WITH CONVENTIONAL SYNTHETIC DISEASE MODIFYING ANTIRHEUMATIC DRUGS IN RHEUMATOID ARTHRITIS: A MULTINATIONAL POPULATION-BASED COHORT FROM 14 REAL WORLD HEALTHCARE DATABASES AND 9 COUNTRIES - REALITY VERSUS GUIDELINES
- 2020
-
Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 327-327
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Treatment guidelines recommend early initiation of csDMARDs following diagnosis of rheumatoid arthritis (RA), with methotrexate (MTX) as first-line therapy. Scarce evidence exists on adherence to this guidanceObjectives:To characterize first-line csDMARD treatment during the first year following an RA diagnosis.Methods:14 real world databases (3 Primary care, 6 primary/secondary care records, 5 claims) from 9 countries were included, all mapped to the OMOP common data model.Patients were included on the earliest event of: 1st diagnosis of RA or 1st DMARD prescription with an RA diagnosis within 30 days. Patients were >18 years-old, required 1+ year pre-index data, and at least 1-year follow-up. Study period covered 2000-2018. Previous users of DMARDs or non-RA inflammatory arthritis history were excluded. Only MTX, Hydroxychloroquine (HCQ), Sulfasalazine (SSZ) and Leflunomide (LEF) were available in all databases.Results:We identified 323,547 eligible participants. Large variation was observed internationally (Figure 1). MTX as first-line monotherapy ranged from 33.3% to 74.5%, and in combination with HCQ from 2.1% to 6.7%. Three additional csDMARDs were used as first-line: HCQ in 10.1% to 30.2%, SSZ in 0.9% to 28.7%, and LEF in 1.8% to 15.2%.Figure 1.First line csDMARD treatment during 1yr from first observed RA diagnosisConclusion:We report wide heterogeneity of first-line csDMARDs regimens internationally. Despite recommendations for MTX to be first line therapy, data suggest that a large proportion of patients receive alternative csDMARD.Disclosure of Interests: :Anthony G Sena Shareholder of: J&J shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Full-time employment salary from Janssen, Employee of: Janssen employee, Paid instructor for: Janssen employee, Speakers bureau: Janssen employee, Denis Granados: None declared, Nigel Hughes Shareholder of: J&J shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Janssen employee, Employee of: Janssen employee, Paid instructor for: Janssen employee, Speakers bureau: Janssen employee, WALID FAKHOURI Shareholder of: E Lilly Shares, Employee of: Eli Lilly and Company, Antje Hottgenroth Shareholder of: Eli Lilly shares, Employee of: Lilly Deutschland GmbH, Raivo Kolde: None declared, Sulev Reisberg: None declared, Carmen Olga Torre: None declared, Talita Duarte-Salles: None declared, Yesika Díaz: None declared, Jose Felipe Golib-Dzib Grant/research support from: Full-time employment salary from Janssen, Employee of: Yes, Janssen employee, Paid instructor for: Janssen Employee, Speakers bureau: Janssen Employee, Emily S. Brouwer Shareholder of: J&J shares, Takeda shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Janssen employee, Employee of: Janssen employee, Paid instructor for: Janssen Employee, Speakers bureau: Janssen Employee, Edward Burn: None declared, Jennifer Lane: None declared, David Vizcaya Employee of: Bayer, Sara Bruce Wirta Employee of: Janssen-Cilag Sweden AB, Marcel de Wilde: None declared, Katia Verhamme: None declared, Peter Rijnbeek: None declared, Elke Theander Employee of: Janssen-Cilag Sweden AB, Katerina Chatzidionysiou Consultant of: AbbVie, Pfizer, Lilly., Daniel Prieto-Alhambra Grant/research support from: Professor Prieto-Alhambra has received research Grants from AMGEN, UCB Biopharma and Les Laboratoires Servier, Consultant of: DPA’s department has received fees for consultancy services from UCB Biopharma, Speakers bureau: DPA’s department has received fees for speaker and advisory board membership services from Amgen, Patrick Ryan: None declared
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
- Drake, A. B., et al.
(författare)
-
The MUSE Hubble Ultra Deep Field Survey VI. The faint-end of the Lyα luminosity function at 2.91
- 2017
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 608
-
Tidskriftsartikel (refereegranskat)abstract
- We present the deepest study to date of the Ly alpha luminosity function in a blank field using blind integral field spectroscopy from MUSE. We constructed a sample of 604 Ly alpha emitters (LAEs) across the redshift range 2.91 < z < 6.64 using automatic detection software in the Hubble Ultra Deep Lield. The deep data cubes allowed us to calculate accurate total Ly alpha fluxes capturing low surface-brightness extended Ly alpha emission now known to be a generic property of high-redshift star-forming galaxies. We simulated realistic extended LAEs to fully characterise the selection function of our samples, and performed flux-recovery experiments to test and correct for bias in our determination of total Ly alpha fluxes. We find that an accurate completeness correction accounting for extended emission reveals a very steep faint-end slope of the luminosity function, alpha, down to luminosities of log(10) L erg s(-1) < 41.5, applying both the 1/V-max and maximum likelihood estimators. Splitting the sample into three broad redshift bins, we see the faint-end slope increasing from -2.03(-0.07)(+1.42) at z approximate to 3.44 to -2.86(-infinity)(+0.76) Z approximate to 76 at z approximate to 5.48, however no strong evolution is seen between the 68% confidence regions in L*-alpha parameter space. Using the Ly alpha line flux as a proxy for star formation activity, and integrating the observed luminosity functions, we find that LAEs' contribution to the cosmic star formation rate density rises with redshift until it is comparable to that from continuum-selected samples by z approximate to 6. This implies that LAEs may contribute more to the star-formation activity of the early Universe than previously thought, as any additional intergalactic medium (IGM) correction would act to further boost the Ly alpha luminosities. Linally, assuming fiducial values for the escape of Ly alpha and LyC radiation, and the dumpiness of the IGM, we integrated the maximum likelihood luminosity function at 5.00 < z < 6.64 and find we require only a small extrapolation beyond the data (<1 dex in luminosity) for LAEs alone to maintain an ionised IGM at z approximate to 6.
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Farzan, N, et al.
(författare)
-
Rationale and design of the multiethnic Pharmacogenomics in Childhood Asthma consortium
- 2017
-
Ingår i: Pharmacogenomics. - : Future Medicine Ltd. - 1744-8042 .- 1462-2416. ; 18:10, s. 931-943
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: International collaboration is needed to enable large-scale pharmacogenomics studies in childhood asthma. Here, we describe the design of the Pharmacogenomics in Childhood Asthma (PiCA) consortium. Materials & methods: Investigators of each study participating in PiCA provided data on the study characteristics by answering an online questionnaire. Results: A total of 21 studies, including 14,227 children/young persons (58% male), from 12 different countries are currently enrolled in the PiCA consortium. Fifty six percent of the patients are Caucasians. In total, 7619 were inhaled corticosteroid users. Among patients from 13 studies with available data on asthma exacerbations, a third reported exacerbations despite inhaled corticosteroid use. In the future pharmacogenomics studies within the consortium, the pharmacogenomics analyses will be performed separately in each center and the results will be meta-analyzed. Conclusion: PiCA is a valuable platform to perform pharmacogenetics studies within a multiethnic pediatric asthma population.
|
|
| 15. |
- Ginolfi, M., et al.
(författare)
-
Detection of companion galaxies around hot dust-obscured hyper-luminous galaxy W0410-0913
- 2022
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- The phase transition between galaxies and quasars is often identified with the rare population of hyper-luminous, hot dust-obscured galaxies. Galaxy formation models predict these systems to grow via mergers, that can deliver large amounts of gas toward their centers, induce intense bursts of star formation and feed their supermassive black holes. Here we report the detection of 24 galaxies emitting Lyman-α emission on projected physical scales of about 400 kpc around the hyper-luminous hot dust-obscured galaxy W0410-0913, at redshift z = 3.631, using Very Large Telescope observations. While this indicates that W0410-0913 evolves in a very dense environment, we do not find clear signs of mergers that could sustain its growth. Data suggest that if mergers occurred, as models expect, these would involve less massive satellites, with only a moderate impact on the internal interstellar medium of W0410-0913, which is sustained by a rotationally-supported fast-rotating molecular disk, as Atacama Large Millimeter Array observations suggest.
|
|
| 16. |
- Guaita, Lucia, et al.
(författare)
-
The Lyman alpha reference sample IV. Morphology at low and high redshift
- 2015
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 576
-
Tidskriftsartikel (refereegranskat)abstract
- Context. The transport of Ly alpha photons in galaxies is a complex process and the conditions under which Ly alpha photons manage to escape from certain galaxies is still under investigation. The Lyman alpha reference sample (LARS) is a sample of 14 local star-forming galaxies, designed to study Ly alpha in detail and relate it to rest-frame UV and optical emission. Aims. With the aim of identifying rest-frame UV and optical properties, which are typical of Ly alpha emitters (LAEs, galaxies with EW(Ly alpha) > 20 angstrom) at both low and high redshift, we investigated the morphological properties of the LARS galaxies, in particular the ones that exhibit intense Ly alpha radiation. Methods. We measured sizes and morphological parameters in the continuum, Ly alpha, and Ha images. We studied morphology by using the Gini coefficient vs. M20 and asymmetry vs. concentration diagrams. We then simulated LARS galaxies at z similar to 2 and 5.7, performing the same morphological measurements. We also investigated the detectability of LARS galaxies in current deep field observations. The subsample of LAEs within LARS (LARS-LAEs) was stacked to provide a comparison to stacking studies performed at high redshift. Results. LARS galaxies have continuum size, stellar mass, and rest-frame absolute magnitude typical of Lyman break analogues in the local Universe and also similar to 2 < z < 3 star-forming galaxies and massive LAEs. LARS optical morphology is consistent with the one of merging systems, and irregular or starburst galaxies. For the first time we quantify the morphology in Ly alpha images: even if a variety of intrinsic conditions of the interstellar medium can favour the escape of Ly alpha photons, LARS-LAEs appear small in the continuum, and their Ly alpha is compact. LARS galaxies tend to be more extended in Ly alpha than in the rest-frame UV. It means that Ly alpha photons escape by forming haloes around HII regions of LARS galaxies. Conclusions. The stack of LARS-LAE Ly alpha images is peaked in the centre, indicating that the conditions, which make a galaxy an LAE, tend to produce a concentrated surface brightness profile. On the other hand, the stack of all LARS galaxies is shallower and more extended. This can be caused by the variety of dust and HI amount and distribution, which produces a more complex, patchy, and extended profile, like the one observed for Lyman break galaxies that can contribute to the stack. We cannot identify a single morphological property that controls whether a galaxy emits a net positive Ly alpha flux. However, the LARS-LAEs have continuum properties consistent with merging systems.
|
|
| 17. |
- Hernandez-Pacheco, N, et al.
(författare)
-
Genome-wide association study of asthma exacerbations despite inhaled corticosteroid use
- 2021
-
Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 57:5
-
Tidskriftsartikel (refereegranskat)abstract
- Substantial variability in response to asthma treatment with inhaled corticosteroids (ICS) has been described among individuals and populations, suggesting the contribution of genetic factors. Nonetheless, only a few genes have been identified to date. We aimed to identify genetic variants associated with asthma exacerbations despite ICS use in European children and young adults and to validate the findings in non-Europeans. Moreover, we explored whether a gene-set enrichment analysis could suggest potential novel asthma therapies.MethodsA genome-wide association study (GWAS) of asthma exacerbations was tested in 2681 children of European descent treated with ICS from eight studies. Suggestive association signals were followed up for replication in 538 European asthma patients. Further evaluation was performed in 1773 non-Europeans. Variants revealed by published GWAS were assessed for replication. Additionally, gene-set enrichment analysis focused on drugs was performed.Results10 independent variants were associated with asthma exacerbations despite ICS treatment in the discovery phase (p≤5×10−6). Of those, one variant at theCACNA2D3-WNT5Alocus was nominally replicated in Europeans (rs67026078; p=0.010), but this was not validated in non-European populations. Five other genes associated with ICS response in previous studies were replicated. Additionally, an enrichment of associations in genes regulated by trichostatin A treatment was found.ConclusionsThe intergenic region ofCACNA2D3andWNT5Awas revealed as a novel locus for asthma exacerbations despite ICS treatment in European populations. Genes associated were related to trichostatin A, suggesting that this drug could regulate the molecular mechanisms involved in treatment response.
|
|
| 18. |
- Kwiecinski, Jakub, 1985, et al.
(författare)
-
Tissue Plasminogen Activator Coating on Implant Surfaces Reduces Staphylococcus aureus Biofilm Formation
- 2016
-
Ingår i: Applied and Environmental Microbiology. - : American Society for Microbiology. - 0099-2240 .- 1098-5336. ; 82:1, s. 394-401
-
Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus aureus biofilm infections of indwelling medical devices are a major medical challenge because of their high prevalence and antibiotic resistance. As fibrin plays an important role in S. aureus biofilm formation, we hypothesize that coating of the implant surface with fibrinolytic agents can be used as a new method of antibiofilm prophylaxis. The effect of tissue plasminogen activator (tPA) coating on S. aureus biofilm formation was tested with in vitro microplate biofilm assays and an in vivo mouse model of biofilm infection. tPA coating efficiently inhibited biofilm formation by various S. aureus strains. The effect was dependent on plasminogen activation by tPA, leading to subsequent local fibrin cleavage. A tPA coating on implant surfaces prevented both early adhesion and later biomass accumulation. Furthermore, tPA coating increased the susceptibility of biofilm infections to antibiotics. In vivo, significantly fewer bacteria were detected on the surfaces of implants coated with tPA than on control implants from mice treated with cloxacillin. Fibrinolytic coatings (e.g., with tPA) reduce S. aureus biofilm formation both in vitro and in vivo, suggesting a novel way to prevent bacterial biofilm infections of indwelling medical devices.
|
|
| 19. |
- North, P. L., et al.
(författare)
-
MUSE- inspired view of the quasar Q2059-360, its Lyman alpha blob, and its neighborhood
- 2017
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 604
-
Tidskriftsartikel (refereegranskat)abstract
- The radio-quiet quasar Q2059-360 at redshift z = 3 : 08 is known to be close to a small Lyman ff blob (LAB) and to be absorbed by a proximate damped Ly ff (PDLA) system. Here, we present the Multi Unit Spectroscopic Explorer (MUSE) integral field spectroscopy follow-up of this quasi-stellar object (QSO). Our primary goal is to characterize this LAB in detail by mapping it both spatially and spectrally using the Ly ff line, and by looking for high-ionization lines to constrain the emission mechanism. Combining the high sensitivity of the MUSE integral field spectrograph mounted on the Yepun telescope at ESO-VLT with the natural coronagraph provided by the PDLA, we map the LAB down to the QSO position, after robust subtraction of QSO light in the spectral domain. In addition to confirming earlier results for the small bright component of the LAB, we unveil a faint filamentary emission protruding to the south over about 80 pkpc (physical kpc); this results in a total size of about 120 pkpc. We derive the velocity field of the LAB (assuming no transfer effects) and map the Ly ff line width. Upper limits are set to the flux of the N v lambda 1238 1242, C iv lambda 1548 1551, Heii lambda 1640, and C i i i] lambda 1548 1551 lines. We have discovered two probable Ly alpha emitters at the same redshift as the LAB and at projected distances of 265 kpc and 207 kpc from the QSO; their Ly alpha luminosities might well be enhanced by the QSO radiation. We also find an emission line galaxy at z = 0 : 33 near the line of sight to the QSO. This LAB shares the same general characteristics as the 17 others surrounding radio-quiet QSOs presented previously. However, there are indications that it may be centered on the PDLA galaxy rather than on the QSO.
|
|
| 20. |
- North, P., et al.
(författare)
-
Polarimetry of the Lyα envelope of the radio-quiet quasar SDSS J124020.91+145535.6
- 2024
-
Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 684
-
Tidskriftsartikel (refereegranskat)abstract
- The radio quiet quasar SDSS J1240+1455 lies at a redshift of z = 3.11, is surrounded by a Lyα blob (LAB), and is absorbed by a proximate damped Lyα system. In order to better define the morphology of the blob and determine its emission mechanism, we gathered deep narrow-band images isolating the Lyα line of this object in linearly polarized light. We provide a deep intensity image of the blob, showing a filamentary structure extending up to 16″ (or 122 physical kpc) in diameter. No significant polarization signal could be extracted from the data, but 95% probability upper limits were defined through simulations. They vary between ∼3% in the central 0.75″ disk (after subtraction of the unpolarized quasar continuum) and ∼10% in the 3.8 − 5.5″ annulus. The low polarization suggests that the Lyα photons are emitted mostly in situ, by recombination and de-excitation in a gas largely ionized by the quasar ultraviolet light, rather than by a central source and scattered subsequently by neutral hydrogen gas. This blob shows no detectable polarization signal, contrary to LAB1, a brighter and more extended blob that is not related to the nearby active galactic nucleus (AGN) in any obvious way, and where a significant polarization signal of about 18% was detected.
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
- Paalvast, M., et al.
(författare)
-
Properties and redshift evolution of star-forming galaxies with high [0 III]/[O II] ratios with MUSE at 0.28 < z < 0.85
- 2018
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 618
-
Tidskriftsartikel (refereegranskat)abstract
- We present a study of the [O III]/[O II] ratios of star-forming galaxies drawn from Multi-Unit Spectroscopic Explorer (MUSE) data spanning a redshift range 0.28 < z < 0.85. Recently discovered Lyman continuum (LyC) emitters have extremely high oxygen line ratios: [O III]lambda 5007/[O II]lambda lambda 3726, 3729 > 4. Here we aim to understand the properties and the occurrences of galaxies with such high line ratios. Combining data from several MUSE Guaranteed Time Observing (GTO) programmes, we select a population of star-forming galaxies with bright emission lines, from which we draw 406 galaxies for our analysis based on their position in the z-dependent star formation rate (SFR) stellar mass (M*) plane. Out of this sample 15 are identified as extreme oxygen emitters based on their [O III]/[O II] ratios (3.7%) and 104 galaxies have [O III]/[O II] > 1 (26%). Our analysis shows no significant correlation between M*, SFR, and the distance from the SFR M, relation with [O III]/[O II]. We find a decrease in the fraction of galaxies with [O III]/[O II] > 1 with increasing M*, however, this is most likely a result of the relationship between [O III]/[O II] and metallicity, rather than between [O III]/[O II] and M. We draw a comparison sample of local analogues with < z > 0.03 from the Sloan Digital Sky Survey, and find similar incidence rates for this sample. In order to investigate the evolution in the fraction of high [O III]/[O II] emitters with redshift, we bin the sample into three redshift subsamples of equal number, but find no evidence for a dependence on redshift. Furthermore, we compare the observed line ratios with those predicted by nebular models with no LyC escape and find that most of the extreme oxygen emitters can be reproduced by low metallicity models. The remaining galaxies are likely LyC emitter candidates.
|
|
| 27. |
|
|
| 28. |
|
|
