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| 2. |
- Naehrlich, L., et al.
(författare)
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Incidence of SARS-CoV-2 in people with cystic fibrosis in Europe between February and June 2020
- 2021
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Ingår i: Journal of Cystic Fibrosis. - : Elsevier BV. - 1569-1993. ; 20:4, s. 566-577
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Tidskriftsartikel (refereegranskat)abstract
- Background: Viral infections can cause significant morbidity in cystic fibrosis (CF). The current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic could therefore have a serious impact on the health of people with CF (pwCF). Methods: We used the 38-country European Cystic Fibrosis Society Patient Registry (ECFSPR) to collect case data about pwCF and SARS-CoV-2 infection. Results: Up to 30 June 2020, 16 countries reported 130 SARS-CoV-2 cases in people with CF, yielding an incidence of 2.70/10 0 0 pwCF. Incidence was higher in lung-transplanted patients (n = 23) versus non transplanted patients (n = 107) (8.43 versus 2.36 cases/10 0 0). Incidence was higher in pwCF versus the age-matched general population in the age groups < 15, 15-24, and 25-49 years (p < 0.001), with similar trends for pwCF with and without lung transplant. Compared to the general population, pwCF (regardless of transplantation status) had significantly higher rates of admission to hospital for all age groups with available data, and higher rates of intensive care, although not statistically significant. Most pwCF recovered (96.2%), however 5 died, of whom 3 were lung transplant recipients. The case fatality rate for pwCF (3.85%, 95% CI: 1.26-8.75) was non-significantly lower than that of the general population (7.46%; p = 0.133). Conclusions: SARS-CoV-2 infection can result in severe illness and death for pwCF, even for younger patients and especially for lung transplant recipients. PwCF should continue to shield from infection and should be prioritized for vaccination. (c) 2021 The Authors. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )
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| 3. |
- Jung, A, et al.
(författare)
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Factors for severe outcomes following SARS-CoV-2 infection in people with cystic fibrosis in Europe
- 2021
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Ingår i: ERJ open research. - : European Respiratory Society (ERS). - 2312-0541. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in people with cystic fibrosis (pwCF) can lead to severe outcomes.MethodsIn this observational study, the European Cystic Fibrosis Society Patient Registry collected data on pwCF and SARS-CoV-2 infection to estimate incidence, describe clinical presentation and investigate factors associated with severe outcomes using multivariable analysis.ResultsUp to December 31, 2020, 26 countries reported information on 828 pwCF and SARS-CoV-2 infection. Incidence was 17.2 per 1000 pwCF (95% CI: 16.0–18.4). Median age was 24 years, 48.4% were male and 9.4% had lung transplants. SARS-CoV-2 incidence was higher in lung-transplanted (28.6; 95% CI: 22.7–35.5) versus non-lung-transplanted pwCF (16.6; 95% CI: 15.4–17.8) (p≤0.001).SARS-CoV-2 infection caused symptomatic illness in 75.7%. Factors associated with symptomatic SARS-CoV-2 infection were age >40 years, at least one F508del mutation and pancreatic insufficiency.Overall, 23.7% of pwCF were admitted to hospital, 2.5% of those to intensive care, and regretfully 11 (1.4%) died. Hospitalisation, oxygen therapy, intensive care, respiratory support and death were 2- to 6-fold more frequent in lung-transplanted versus non-lung-transplanted pwCF.Factors associated with hospitalisation and oxygen therapy were lung transplantation, cystic fibrosis-related diabetes (CFRD), moderate or severe lung disease and azithromycin use (often considered a surrogate marker for Pseudomonas aeruginosa infection and poorer lung function).ConclusionSARS-CoV-2 infection yielded high morbidity and hospitalisation in pwCF. PwCF with forced expiratory volume in 1 s <70% predicted, CFRD and those with lung transplants are at particular risk of more severe outcomes.
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| 4. |
- Almani, T., et al.
(författare)
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Convergence of the undrained split iterative scheme for coupling flow with geomechanics in heterogeneous poroelastic media
- 2019
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Ingår i: Computational Geosciences. - : Springer. - 1420-0597 .- 1573-1499. ; 24:2, s. 551-569
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Tidskriftsartikel (refereegranskat)abstract
- Recently, an accurate coupling between subsurface flow and reservoir geomechanics has received more attention in both academia and industry. This stems from the fact that incorporating a geomechanics model into upstream flow simulation is critical for accurately predicting wellbore instabilities and hydraulic fracturing processes. One of the recently introduced iterative coupling algorithms to couple flow with geomechanics is the undrained split iterative coupling algorithm as reported by Kumar et al. (2016) and Mikelic and Wheeler (Comput. Geosci. 17: 455–461 2013). The convergence of this scheme is established in Mikelic and Wheeler (Comput. Geosci. 17:455–461 2013) for the single rate iterative coupling algorithm and in Kumar et al. (2016) for the multirate iterative coupling algorithm, in which the flow takes multiple finer time steps within one coarse mechanics time step. All previously established results study the convergence of the scheme in homogeneous poroelastic media. In this work, following the approach in Almani et al. (2017), we extend these results to the case of heterogeneous poroelastic media, in which each grid cell is associated with its own set of flow and mechanics parameters for both the single rate and multirate schemes. Second, following the approach in Almani et al. (Comput. Geosci. 21:1157–1172 2017), we establish a priori error estimates for the single rate case of the scheme in homogeneous poroelastic media. To the best of our knowledge, this is the first rigorous and complete mathematical analysis of the undrained split iterative coupling scheme in heterogeneous poroelastic media.
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| 5. |
- Kojima, T, et al.
(författare)
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The Effects of High Molecular Weight Hyaluronic Acid Eye Drop Application in Environmental Dry Eye Stress Model Mice
- 2020
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 21:10
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Tidskriftsartikel (refereegranskat)abstract
- Hyaluronic acid (HA) ophthalmic solution is widely used in dry eye treatment worldwide. However, there are no reports comparing the dry eye treatment effects of high molecular weight HA with low molecular weight HA. Sixty eight-week-old C57BL/6 mice were assigned to the following 6 groups and exposed to environmental dry eye stress (EDES) that mimics office work environment: (1) 0.1% low molecular weight HA (LMWHA) eye drops, (2) 0.3% LMWHA eye drops, (3) 3% diquafosol sodium (DQ) eye drops, (4) 0.15% high molecular weight HA (HMWHA) eye drops, (5) no treatment with exposure to EDES (EDES+/Treatment−), and (6) no treatment without exposure to EDES (EDES−/Treatment−). After EDES, the HMWHA group had significantly longer break-up time (BUT) than the 0.1%, 0.3% LMWHA groups and the DQ group. After EDES, the HMWHA group had significantly lower lissamine green staining scores than the LMWHA and DQ groups. Subepithelial presumed dendritic cell density in the HMWHA group was significantly lower than the EDES+/Treatment− group. After EDES exposure, Conjunctival Muc5AC mRNA expression in the HMWHA group was significantly higher than the 0.1 and 0.3% LMWHA groups. Ophthalmic HMWHA solution may have a better dry eye treatment effect than LMWHA or DQ solution, owing to its anti-inflammatory effect.
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| 6. |
- Popichenko, Dmitry, et al.
(författare)
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Jeb/Alk signalling regulates the Lame duck GLI family transcription factor in the Drosophila visceral mesoderm
- 2013
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Ingår i: Development. - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 140:15, s. 3156-3166
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Tidskriftsartikel (refereegranskat)abstract
- The Jelly belly (Jeb)/Anaplastic Lymphoma Kinase (Alk) signalling pathway regulates myoblast fusion in the circular visceral mesoderm (VM) of Drosophila embryos via specification of founder cells. However, only a limited number of target molecules for this pathway are described. We have investigated the role of the Lame Duck (Lmd) transcription factor in VM development in relationship to Jeb/Alk signal transduction. We show that Alk signalling negatively regulates Lmd activity post-transcriptionally through the MEK/MAPK (ERK) cascade resulting in a relocalisation of Lmd protein from the nucleus to cytoplasm. It has previously been shown that downregulation of Lmd protein is necessary for the correct specification of founder cells. In the visceral mesoderm of lmd mutant embryos, fusion-competent myoblasts seem to be converted to 'founder-like' cells that are still able to build a gut musculature even in the absence of fusion. The ability of Alk signalling to downregulate Lmd protein requires the N-terminal 140 amino acids, as a Lmd(141-866) mutant remains nuclear in the presence of active ALK and is able to drive robust expression of the Lmd downstream target Vrp1 in the developing VM. Our results suggest that Lmd is a target of Jeb/Alk signalling in the VM of Drosophila embryos.
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| 8. |
- Villforth, C., et al.
(författare)
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Variability and stability in blazar jets on time-scales of years : optical polarization monitoring of OJ 287 in 2005-2009
- 2010
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 402:3, s. 2087-2111
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Tidskriftsartikel (refereegranskat)abstract
- OJ 287 is a BL Lac object at redshift z = 0.306 that has shown double-peaked bursts at regular intervals of similar to 12 yr during the last similar to 40 yr. We analyse optical photopolarimetric monitoring data from 2005 to 2009, during which the latest double-peaked outburst occurred. The aim of this study is twofold: firstly, we aim to analyse variability patterns and statistical properties of the optical polarization light curve. We find a strong preferred position angle in optical polarization. The preferred position angle can be explained by separating the jet emission into two components: an optical polarization core and chaotic jet emission. The optical polarization core is stable on time-scales of years and can be explained as emission from an underlying quiescent jet component. The chaotic jet emission sometimes exhibits a circular movement in the Stokes plane. We find six such events, all on the time-scales of 10-20 d. We interpret these events as a shock front moving forwards and backwards in the jet, swiping through a helical magnetic field. Secondly, we use our data to assess different binary black hole models proposed to explain the regularly appearing double-peaked bursts in OJ 287. We compose a list of requirements a model has to fulfil to explain the mysterious behaviour observed in OJ 287. The list includes not only characteristics of the light curve but also other properties of OJ 287, such as the black hole mass and restrictions on accretion flow properties. We rate all existing models using this list and conclude that none of the models is able to explain all observations. We discuss possible new explanations and propose a new approach to understanding OJ 287. We suggest that both the double-peaked bursts and the evolution of the optical polarization position angle could be explained as a sign of resonant accretion of magnetic field lines, a 'magnetic breathing' of the disc.
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| 9. |
- Yamazaki, Yasuo, et al.
(författare)
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Goliath family E3 ligases regulate the recycling endosome pathway via VAMP3 ubiquitylation
- 2013
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Ingår i: EMBO Journal. - : Nature Publishing Group. - 0261-4189 .- 1460-2075. ; 32:4, s. 524-537
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Tidskriftsartikel (refereegranskat)abstract
- Diverse cellular processes depend on endocytosis, intracellular vesicle trafficking, sorting and exocytosis, processes regulated post-transcriptionally by modifications such as phosphorylation and ubiquitylation. In addition to sorting to the lysosome, cargo is recycled to the plasma membrane via recycling endosomes. Here, we describe a role of the goliath gene family of protease-associated (PA) domain E3 ligases in regulating recycling endosome trafficking. The two Drosophila members of this family-Goliath and Godzilla(CG10277) - are located on endosomes, and both ectopic expression and loss-of-function lead to the accumulation of Rab5-positive giant endosomes. Furthermore, the human homologue RNF167 exhibits similar behaviour. We show that the soluble N-ethylmaleimide-sensitive fusion attachment protein receptor (SNARE) protein VAMP3 is a target of these ubiquitin ligases, and that recycling endosome trafficking is abrogated in response to their activity. Furthermore, mutation of the Godzilla ubiquitylation target lysines on VAMP3 abrogates the formation of enlarged endosomes induced by either Godzilla or RNF167. Thus, Goliath ubiquitin ligases play a novel role in regulating recycling endosome trafficking via ubiquitylation of the VAMP3 SNARE protein.
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