| 1. |
- Aad, G., et al.
(författare)
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- 2010
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swepub:Mat__t
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| 2. |
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| 3. |
- Ederle, Joerg, et al.
(författare)
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Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
- 2010
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Ingår i: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
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Tidskriftsartikel (refereegranskat)abstract
- Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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| 4. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 5. |
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| 6. |
- Bruzzi, M, et al.
(författare)
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Radiation-hard semiconductor detectors for SuperLHC
- 2005
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002. ; 541:1-2, s. 189-201
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Tidskriftsartikel (refereegranskat)abstract
- An option of increasing the luminosity of the Large Hadron Collider (LHC) at CERN to 1035 cm-2 s-1 has been envisaged to extend the physics reach of the machine. An efficient tracking down to a few centimetres from the interaction point will be required to exploit the physics potential of the upgraded LHC. As a consequence, the semiconductor detectors close to the interaction region will receive severe doses of fast hadron irradiation and the inner tracker detectors will need to survive fast hadron fluences of up to above 1016cm-2. The CERN-RD50 project "Development of Radiation Hard Semiconductor Devices for Very High Luminosity Colliders" has been established in 2002 to explore detector materials and technologies that will allow to operate devices up to, or beyond, this limit. The strategies followed by RD50 to enhance the radiation tolerance include the development of new or defect engineered detector materials (SiC, GaN, Czochralski and epitaxial silicon, oxygen enriched Float Zone silicon), the improvement of present detector designs and the understanding of the microscopic defects causing the degradation of the irradiated detectors. The latest advancements within the RD50 collaboration on radiation hard semiconductor detectors will be reviewed and discussed in this work.
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| 7. |
- Botvinik-Nezer, Rotem, et al.
(författare)
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Variability in the analysis of a single neuroimaging dataset by many teams
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 582, s. 84-88
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Tidskriftsartikel (refereegranskat)abstract
- Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed. The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
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| 8. |
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| 9. |
- Kuhle, J., et al.
(författare)
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Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study
- 2015
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Ingår i: Multiple Sclerosis Journal. - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 21:8, s. 1013-1024
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. Methods: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years' follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. Results: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71-2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52-2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04-3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98-0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres. Conclusions: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.
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| 10. |
- Shrine, N, et al.
(författare)
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Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk
- 2023
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 55:3, s. 410-
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Tidskriftsartikel (refereegranskat)abstract
- Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.
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| 11. |
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| 13. |
- Fabian, ID, et al.
(författare)
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Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European countries
- 2021
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Ingår i: The British journal of ophthalmology. - : BMJ. - 1468-2079 .- 0007-1161. ; 105:10, s. 1435-1443
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Tidskriftsartikel (refereegranskat)abstract
- The travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe.MethodsA cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries.ResultsCapture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI −12.4 to −5.4, p<0.001), had fewer cases of familial retinoblastoma (95% CI 2.0 to 5.3, p<0.001) and presented with more advanced disease (95% CI 6.0 to 9.8, p<0.001); 43.4% and 15.4% of Africans had extraocular retinoblastoma and distant metastasis at the time of diagnosis, respectively, compared to 2.9% and 1.0% of the Europeans. To reach a retinoblastoma centre, European patients travelled 421.8 km compared to Africans who travelled 185.7 km (p<0.001). On regression analysis, lower-national income level, African residence and older age (p<0.001), but not travel distance (p=0.19), were risk factors for advanced disease.ConclusionsFewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral.
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| 14. |
- Benjamin, L. A., et al.
(författare)
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Antiphospholipid antibodies and neurological manifestations in acute COVID-19: A single-centre cross-sectional study
- 2021
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Ingår i: Eclinicalmedicine. - : Elsevier BV. - 2589-5370. ; 39
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Tidskriftsartikel (refereegranskat)abstract
- Background: A high prevalence of antiphospholipid antibodies has been reported in case series of patients with neurological manifestations and COVID-19; however, the pathogenicity of antiphospholipid antibodies in COVID-19 neurology remains unclear. Methods: This single-centre cross-sectional study included 106 adult patients: 30 hospitalised COVID-neurological cases, 47 non-neurological COVID-hospitalised controls, and 29 COVID-non-hospitalised controls, recruited between March and July 2020. We evaluated nine antiphospholipid antibodies: anticardiolipin antibodies [aCL] IgA, IgM, IgG; anti-beta-2 glycoprotein-1 [a beta(2)GPI] IgA, IgM, IgG; anti-phosphatidylserine/prothrombin [aPS/PT] IgM, IgG; and anti-domain I b2GPI (aD1 beta 2GPI) IgG. Findings: There was a high prevalence of antiphospholipid antibodies in the COVID-neurological (73.3%) and non-neurological COVID-hospitalised controls (76.6%) in contrast to the COVID-non-hospitalised controls (48.2%). aPS/PT IgG titres were significantly higher in the COVID-neurological group compared to both control groups (p < 0.001). Moderate-high titre of aPS/PT IgG was found in 2 out of 3 (67%) patients with acute disseminated encephalomyelitis [ADEM]. aPS/PT IgG titres negatively correlated with oxygen requirement (FiO(2) R=-0.15 p = 0.040) and was associated with venous thromboembolism (p = 0.043). In contrast, aCL IgA (p < 0.001) and IgG (p < 0.001) was associated with non-neurological COVID-hospitalised controls compared to the other groups and correlated positively with D-dimer and creatinine but negatively with FiO(2). Interpretation: Our findings show that aPS/PT IgG is associated with COVID-19-associated ADEM. In contrast, aCL IgA and IgG are seen much more frequently in non-neurological hospitalised patients with COVID-19. Characterisation of antiphospholipid antibody persistence and potential longitudinal clinical impact are required to guide appropriate management. (C) 2021 The Author(s). Published by Elsevier Ltd.
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| 15. |
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| 16. |
- Galluzzi, L, et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes.
- 2009
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Ingår i: Cell death and differentiation. - : Springer Science and Business Media LLC. - 1476-5403 .- 1350-9047. ; 16:8, s. 1093-107
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Forskningsöversikt (refereegranskat)abstract
- Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases. Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies. It is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/or in tissues, from model organisms and/or humans, in healthy and/or pathological scenarios. Thus far, dozens of methods have been proposed to quantify cell death-related parameters. However, no guidelines exist regarding their use and interpretation, and nobody has thoroughly annotated the experimental settings for which each of these techniques is most appropriate. Here, we provide a nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls. These guidelines are intended for investigators who study cell death, as well as for reviewers who need to constructively critique scientific reports that deal with cellular demise. Given the difficulties in determining the exact number of cells that have passed the point-of-no-return of the signaling cascades leading to cell death, we emphasize the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells.
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| 17. |
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| 18. |
- Psaridi, A., et al.
(författare)
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Discovery of two warm mini-Neptunes with contrasting densities orbiting the young K3V star TOI-815
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 685
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Tidskriftsartikel (refereegranskat)abstract
- We present the discovery and characterization of two warm mini-Neptunes transiting the K3V star TOI-815 in a K–M binary system. Analysis of its spectra and rotation period reveal the star to be young, with an age of 200+−400200 Myr. TOI-815b has a 11.2-day period and a radius of 2.94 ± 0.05 R+ with transits observed by TESS, CHEOPS, ASTEP, and LCOGT. The outer planet, TOI-815c, has a radius of 2.62 ± 0.10 R+, based on observations of three nonconsecutive transits with TESS; targeted CHEOPS photometry and radial velocity follow-up with ESPRESSO were required to confirm the 35-day period. ESPRESSO confirmed the planetary nature of both planets and measured masses of 7.6 ± 1.5 M+ (ρP = 1.64+−003331 g cm−3) and 23.5 ± 2.4 M+ (ρP = 7.2+−1110 g cm−3), respectively. Thus, the planets have very different masses, which is unusual for compact multi-planet systems. Moreover, our statistical analysis of mini-Neptunes orbiting FGK stars suggests that weakly irradiated planets tend to have higher bulk densities compared to those undergoing strong irradiation. This could be ascribed to their cooler atmospheres, which are more compressed and denser. Internal structure modeling of TOI-815b suggests it likely has a H-He atmosphere that constitutes a few percent of the total planet mass, or higher if the planet is assumed to have no water. In contrast, the measured mass and radius of TOI-815c can be explained without invoking any atmosphere, challenging planetary formation theories. Finally, we infer from our measurements that the star is viewed close to pole-on, which implies a spin-orbit misalignment at the 3σ level. This emphasizes the peculiarity of the system’s orbital architecture, and probably hints at an eventful dynamical history.
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| 19. |
- Schiller, D, et al.
(författare)
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The Human Affectome
- 2024
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Ingår i: Neuroscience and biobehavioral reviews. - 1873-7528. ; 158, s. 105450-
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Tidskriftsartikel (refereegranskat)
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| 20. |
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| 21. |
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| 25. |
- Osborn, H. P., et al.
(författare)
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Uncovering the true periods of the young sub-Neptunes orbiting TOI-2076
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 664
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Tidskriftsartikel (refereegranskat)abstract
- Context. TOI-2076 is a transiting three-planet system of sub-Neptunes orbiting a bright (G = 8.9 mag), young (340 +/- 80 Myr) K-type star. Although a validated planetary system, the orbits of the two outer planets were unconstrained as only two non-consecutive transits were seen in TESS photometry. This left 11 and 7 possible period aliases for each. Aims. To reveal the true orbits of these two long-period planets, precise photometry targeted on the highest-probability period aliases is required. Long-term monitoring of transits in multi-planet systems can also help constrain planetary masses through TTV measurements. Methods. We used the MonoTools package to determine which aliases to follow, and then performed space-based and ground-based photometric follow-up of TOI-2076 c and d with CHEOPS, SAINT-EX, and LCO telescopes. Results. CHEOPS observations revealed a clear detection for TOI-2076 c at P = 21.01538(-0.00074)(+0.00084) d, and allowed us to rule out three of the most likely period aliases for TOI-2076 d. Ground-based photometry further enabled us to rule out remaining aliases and confirm the P = 35.12537 +/- 0.00067 d alias. These observations also improved the radius precision of all three sub-Neptunes to 2.518 +/- 0.036, 3.497 +/- 0.043, and 3.232 +/- 0.063 R-circle plus. Our observations also revealed a clear anti-correlated TTV signal between planets b and c likely caused by their proximity to the 2:1 resonance, while planets c and d appear close to a 5:3 period commensurability, although model degeneracy meant we were unable to retrieve robust TTV masses. Their inflated radii, likely due to extended H-He atmospheres, combined with low insolation makes all three planets excellent candidates for future comparative transmission spectroscopy with JWST.
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| 26. |
- Tuson, A., et al.
(författare)
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TESS and CHEOPS discover two warm sub-Neptunes transiting the bright K-dwarf HD 15906
- 2023
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Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 523:2, s. 3090-3118
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of two warm sub-Neptunes transiting the bright (G = 9.5 mag) K-dwarf HD 15906 (TOI 461, TIC 4646810). This star was observed by the Transiting Exoplanet Survey Satellite (TESS) in sectors 4 and 31, revealing two small transiting planets. The inner planet, HD 15906 b, was detected with an unambiguous period but the outer planet, HD 15906 c, showed only two transits separated by ∼ 734 d, leading to 36 possible values of its period. We performed follow-up observations with the CHaracterising ExOPlanet Satellite (CHEOPS) to confirm the true period of HD 15906 c and improve the radius precision of the two planets. From TESS, CHEOPS, and additional ground-based photometry, we find that HD 15906 b has a radius of 2.24 ± 0.08 R and a period of 10.924709 ± 0.000032 d, whilst HD 15906 c has a radius of 2.93+−000607 R and a period of 21.583298+−00000055000052 d. Assuming zero bond albedo and full day-night heat redistribution, the inner and outer planet have equilibrium temperatures of 668 ± 13 K and 532 ± 10 K, respectively. The HD 15906 system has become one of only six multiplanet systems with two warm (700 K) sub-Neptune sized planets transiting a bright star (G ≤ 10 mag). It is an excellent target for detailed characterization studies to constrain the composition of sub-Neptune planets and test theories of planet formation and evolution.
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| 31. |
- Osborn, H. P., et al.
(författare)
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Two warm Neptunes transiting HIP 9618 revealed by TESS and Cheops
- 2023
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Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 523:2, s. 3069-3089
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Tidskriftsartikel (refereegranskat)abstract
- HIP 9618 (HD 12572, TOI-1471, TIC 306263608) is a bright (G = 9.0 mag) solar analogue. TESS photometry revealed the star to have two candidate planets with radii of 3.9 ± 0.044 R (HIP 9618 b) and 3.343 ± 0.039 R (HIP 9618 c). While the 20.77291 d period of HIP 9618 b was measured unambiguously, HIP 9618 c showed only two transits separated by a 680-d gap in the time series, leaving many possibilities for the period. To solve this issue, CHEOPS performed targeted photometry of period aliases to attempt to recover the true period of planet c, and successfully determined the true period to be 52.56349 d. High-resolution spectroscopy with HARPS-N, SOPHIE, and CAFE revealed a mass of 10.0 ± 3.1M for HIP 9618 b, which, according to our interior structure models, corresponds to a 6.8 ± 1.4 per cent gas fraction. HIP 9618 c appears to have a lower mass than HIP 9618 b, with a 3-sigma upper limit of <18M. Follow-up and archival RV measurements also reveal a clear long-term trend which, when combined with imaging and astrometric information, reveal a low-mass companion (0.08+−000512M☉) orbiting at 26.0+−111900 au. This detection makes HIP 9618 one of only five bright (K < 8 mag) transiting multiplanet systems known to host a planet with P > 50 d, opening the door for the atmospheric characterization of warm (Teq < 750 K) sub-Neptunes.
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| 32. |
- Underwood, J, et al.
(författare)
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Validation of a Novel Multivariate Method of Defining HIV-Associated Cognitive Impairment
- 2019
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Ingår i: Open forum infectious diseases. - : Oxford University Press (OUP). - 2328-8957. ; 6:6, s. ofz198-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient– reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts.MethodsDifferences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria.ResultsThe prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment (P < .05).There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres (P < .05), as well as smaller brain volumes (P < .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker.ConclusionDifferent methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach.
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| 34. |
- Barros, S. C. C., et al.
(författare)
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Detection of the tidal deformation of WASP-103b at 3σ with CHEOPS
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 657
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Tidskriftsartikel (refereegranskat)abstract
- Context. Ultra-short period planets undergo strong tidal interactions with their host star which lead to planet deformation and orbital tidal decay.Aims. WASP-103b is the exoplanet with the highest expected deformation signature in its transit light curve and one of the shortest expected spiral-in times. Measuring the tidal deformation of the planet would allow us to estimate the second degree fluid Love number and gain insight into the planet's internal structure. Moreover, measuring the tidal decay timescale would allow us to estimate the stellar tidal quality factor, which is key to constraining stellar physics.Methods. We obtained 12 transit light curves of WASP-103b with the CHaracterising ExOplanet Satellite (CHEOPS) to estimate the tidal deformation and tidal decay of this extreme system. We modelled the high-precision CHEOPS transit light curves together with systematic instrumental noise using multi-dimensional Gaussian process regression informed by a set of instrumental parameters. To model the tidal deformation, we used a parametrisation model which allowed us to determine the second degree fluid Love number of the planet. We combined our light curves with previously observed transits of WASP-103b with the Hubble Space Telescope (HST) and Spitzer to increase the signal-to-noise of the light curve and better distinguish the minute signal expected from the planetary deformation.Results. We estimate the radial Love number of WASP-103b to be h(f) = 1.59(-0.53)(+0.45). This is the first time that the tidal deformation is directly detected (at 3 sigma) from the transit light curve of an exoplanet. Combining the transit times derived from CHEOPS, HST, and Spitzer light curves with the other transit times available in the literature, we find no significant orbital period variation for WASP-103b. However, the data show a hint of an orbital period increase instead of a decrease, as is expected for tidal decay. This could be either due to a visual companion star if this star is bound, the Applegate effect, or a statistical artefact.Conclusions. The estimated Love number of WASP-103b is similar to Jupiter's. This will allow us to constrain the internal structure and composition of WASP-103b, which could provide clues on the inflation of hot Jupiters. Future observations with James Webb Space Telescope can better constrain the radial Love number of WASP-103b due to their high signal-to-noise and the smaller signature of limb darkening in the infrared. A longer time baseline is needed to constrain the tidal decay in this system.
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| 35. |
- Catar, R, et al.
(författare)
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Expanded Hemodialysis Therapy Ameliorates Uremia-Induced Systemic Microinflammation and Endothelial Dysfunction by Modulating VEGF, TNF-α and AP-1 Signaling
- 2021
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 12, s. 774052-
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Tidskriftsartikel (refereegranskat)abstract
- Systemic chronic microinflammation and altered cytokine signaling, with adjunct cardiovascular disease (CVD), endothelial maladaptation and dysfunction is common in dialysis patients suffering from end-stage renal disease and associated with increased morbidity and mortality. New hemodialysis filters might offer improvements. We here studied the impact of novel improved molecular cut-off hemodialysis filters on systemic microinflammation, uremia and endothelial dysfunction. Human endothelial cells (ECs) were incubated with uremic serum obtained from patients treated with two different hemodialysis regimens in the Permeability Enhancement to Reduce Chronic Inflammation (PERCI-II) crossover clinical trial, comparing High-Flux (HF) and Medium Cut-Off (MCO) membranes, and then assessed for their vascular endothelial growth factor (VEGF) production and angiogenesis. Compared to HF membranes, dialysis with MCO membranes lead to a reduction in proinflammatory mediators and reduced endothelial VEGF production and angiogenesis. Cytokine multiplex screening identified tumor necrosis factor (TNF) superfamily members as promising targets. The influence of TNF-α and its soluble receptors (sTNF-R1 and sTNF-R2) on endothelial VEGF promoter activation, protein release, and the involved signaling pathways was analyzed, revealing that this detrimental signaling was indeed induced by TNF-α and mediated by AP-1/c-FOS signaling. In conclusion, uremic toxins, in particular TNF-signaling, promote endothelial maladaptation, VEGF expression and aberrant angiogenesis, which can be positively modulated by dialysis with novel MCO membranes.Translational Perspective and Graphical AbstractSystemic microinflammation, altered cytokine signaling, cardiovascular disease, and endothelial maladaptation/dysfunction are common clinical complications in dialysis patients suffering from end-stage renal disease. We studied the impact of novel improved medium-cut-off hemodialysis filters on uremia and endothelial dysfunction. We can show that uremic toxins, especially TNF-signaling, promote endothelial maladaptation, VEGF expression and aberrant angiogenesis, which can be positively modulated by dialysis with novel improved medium-cut-off membranes.
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| 36. |
- Engler, N., et al.
(författare)
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The high-albedo, low polarization disk around HD 114082 that harbors a Jupiter-sized transiting planet Constraints from VLT/SPHERE completed with TESS, Gaia, and radial velocities
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 672
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Tidskriftsartikel (refereegranskat)abstract
- Aims. We present new optical and near-infrared images of the debris disk around the F-type star HD 114082 in the Scorpius-Centaurus OB association. We obtained direct imaging observations and analyzed the TESS photometric time series data of this target with the goal of searching for planetary companions to HD 114082 and characterizing the morphology of the debris disk and the scattering properties of dust particles. Methods. HD 114082 was observed with the VLT/SPHERE instrument in different modes - the IRDIS camera in the K band (2.0-2.3 mu m) together with the IFS in the Y, J, and H bands (0.95-1.66 mu m) using the angular differential imaging technique as well as IRDIS in the H band (1.5-1.8 mu m) and ZIMPOL in the I_PRIME band (0.71-0.87 mu m) using the polarimetric differential imaging technique. To constrain the basic geometrical parameters of the disk and the scattering properties of dust grains, scattered light images were fitted with a 3D model for single scattering in an optically thin dust disk using a Markov chain Monte Carlo approach. We performed aperture photometry to derive the scattering and polarized phase functions, the polarization fraction, and the spectral scattering albedo for the dust particles in the disk. This method was also used to obtain the reflectance spectrum of the disk and, in turn, to retrieve the disk color and study the dust reflectivity in comparison to the debris disk HD 117214. We also performed the modeling of the HD 114082 light curve measured by TESS using models for planet transit and stellar activity to put constraints on the radius of the detected planet and its orbit. Last, we searched for additional planets in the system by combining archival radial velocity data, astrometry, and direct imaging. Results. The debris disk HD 114082 appears as an axisymmetric debris belt with a radius of similar to 0.37 '' (35 au), an inclination of similar to 83 degrees, and a wide inner cavity. Dust particles in HD 114082 have a maximum polarization fraction of similar to 17% and a higher reflectivity when compared to the debris disk HD 117214. This high reflectivity results in a spectral scattering albedo of similar to 0.65 for the HD 114082 disk at near-infrared wavelengths. The disk reflectance spectrum exhibits a red color at the position of the planetesimal belt and shows no obvious features, whereas that of HD 117214 might indicate the presence of CO2 ice. The analysis of TESS photometric data reveals a transiting planetary companion to HD 114082 with a radius of similar to 1 R-Jup on an orbit with a semimajor axis of 0.7 +/- 0.4 au. No additional planet was detected in the system when we combined the SPHERE images with constraints from astrometry and radial velocity. We reach deep sensitivity limits down to similar to 5 M-Jup at 50 au and similar to 10 M-Jup at 30 au from the central star.
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| 37. |
- Rose, K, et al.
(författare)
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Responses of paediatric emergency departments to the first wave of the COVID-19 pandemic in Europe: a cross-sectional survey study
- 2021
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Ingår i: BMJ paediatrics open. - : BMJ. - 2399-9772. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Understanding how paediatric emergency departments (PEDs) across Europe adapted their healthcare pathways in response to COVID-19 will help guide responses to ongoing waves of COVID-19 and potential future pandemics. This study aimed to evaluate service reconfiguration across European PEDs during the initial COVID-19 wave.DesignThis cross-sectional survey included 39 PEDs in 17 countries. The online questionnaire captured (1) study site characteristics, (2) departmental changes and (3) pathways for children with acute illness pre and during the first wave of COVID-19 pandemic (January–May 2020). Number of changes to health services, as a percentage of total possible changes encompassed by the survey, was compared with peak national SARS-CoV-2 incidence rates, and for both mixed and standalone paediatric centres.ResultsOverall, 97% (n=38) of centres remained open as usual during the pandemic. The capacity of 18 out of 28 (68%) short-stay units decreased; in contrast, 2 units (7%) increased their capacity. In 12 (31%) PEDs, they reported acting as receiving centres for diverted children during the pandemic.There was minimal change to the availability of paediatric consultant telephone advice services, consultant supervision of juniors or presence of responsible specialists within the PEDs.There was no relationship between percentage of possible change at each site and the peak national SARS-CoV-2 incidence rate. Mixed paediatric and adult hospitals made 8% of possible changes and standalone paediatric centres made 6% of possible changes (p=0.086).ConclusionOverall, there was limited change to the organisation or delivery of services across surveyed PEDs during the first wave of the COVID-19 pandemic.
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| 38. |
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| 39. |
- Szabo, Gy M., et al.
(författare)
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Transit timing variations of AU Microscopii b and c*
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 659
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Tidskriftsartikel (refereegranskat)abstract
- Here we report large-amplitude transit timing variations (TTVs) for AU Microcopii b and c as detected in combined TESS (2018, 2020) and CHEOPS (2020, 2021) transit observations. AU Mic is a young planetary system with a debris disk and two transiting warm Neptunes. A TTV on the order of several minutes was previously reported for AU Mic b, which was suggested to be an outcome of mutual perturbations between the planets in the system. In 2021, we observed AU Mic b (five transits) and c (three transits) with the CHEOPS space telescope to follow-up the TTV of AU Mic b and possibly detect a TTV for AU Mic c. When analyzing TESS and CHEOPS 2020-2021 measurements together, we find that a prominent TTV emerges with a full span of >= 23 min between the two TTV extrema. Assuming that the period change results from a periodic process -such as mutual perturbations- we demonstrate that the times of transits in the summer of 2022 are expected to be 30-85 min later than predicted by the available linear ephemeris.
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| 40. |
- Ulmer-Moll, S., et al.
(författare)
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TOI-5678b: A 48-day transiting Neptune-mass planet characterized with CHEOPS and HARPS
- 2023
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 674
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Tidskriftsartikel (refereegranskat)abstract
- Context. A large sample of long-period giant planets has been discovered thanks to long-term radial velocity surveys, but only a few dozen of these planets have a precise radius measurement. Transiting gas giants are crucial targets for the study of atmospheric composition across a wide range of equilibrium temperatures and, more importantly, for shedding light on the formation and evolution of planetary systems. Indeed, compared to hot Jupiters, the atmospheric properties and orbital parameters of cooler gas giants are unaltered by intense stellar irradiation and tidal effects. Aims. We aim to identify long-period planets in the Transiting Exoplanet Survey Satellite (TESS) data as single or duo-transit events. Our goal is to solve the orbital periods of TESS duo-transit candidates with the use of additional space-based photometric observations and to collect follow-up spectroscopic observations in order to confirm the planetary nature and measure the mass of the candidates. Methods. We use the CHaracterising ExOPlanet Satellite (CHEOPS) to observe the highest-probability period aliases in order to discard or confirm a transit event at a given period. Once a period is confirmed, we jointly model the TESS and CHEOPS light curves along with the radial velocity datasets to measure the orbital parameters of the system and obtain precise mass and radius measurements. Results. We report the discovery of a long-period transiting Neptune-mass planet orbiting the G7-type star TOI-5678. Our spectroscopic analysis shows that TOI-5678 is a star with a solar metallicity. The TESS light curve of TOI-5678 presents two transit events separated by almost two years. In addition, CHEOPS observed the target as part of its Guaranteed Time Observation program. After four non-detections corresponding to possible periods, CHEOPS detected a transit event matching a unique period alias. Follow-up radial velocity observations were carried out with the ground-based high-resolution spectrographs CORALIE and HARPS. Joint modeling reveals that TOI-5678 hosts a 47.73 day period planet, and we measure an orbital eccentricity consistent with zero at 2σ. The planet TOI-5678 b has a mass of 20 ± 4 Earth masses (M) and a radius of 4.91 ± 0.08 R Using interior structure modeling, we find that TOI-5678 b is composed of a low-mass core surrounded by a large H/He layer with a mass of 3.2±1.7-1.3 M. Conclusions. TOI-5678 b is part of a growing sample of well-characterized transiting gas giants receiving moderate amounts of stellar insolation (11 S). Precise density measurement gives us insight into their interior composition, and the objects orbiting bright stars are suitable targets to study the atmospheric composition of cooler gas giants.
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| 41. |
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| 46. |
- Garai, Z., et al.
(författare)
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Refined parameters of the HD 22946 planetary system and the true orbital period of planet d
- 2023
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 674
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Tidskriftsartikel (refereegranskat)abstract
- Context. Multi-planet systems are important sources of information regarding the evolution of planets. However, the long-period planets in these systems often escape detection. These objects in particular may retain more of their primordial characteristics compared to close-in counterparts because of their increased distance from the host star. HD 22946 is a bright (G = 8.13 mag) late F-type star around which three transiting planets were identified via Transiting Exoplanet Survey Satellite (TESS) photometry, but the true orbital period of the outermost planet d was unknown until now. Aims. We aim to use the Characterising Exoplanet Satellite (CHEOPS) space telescope to uncover the true orbital period of HD 22946d and to refine the orbital and planetary properties of the system, especially the radii of the planets. Methods. We used the available TESS photometry of HD 22946 and observed several transits of the planets b, c, and d using CHEOPS. We identified two transits of planet d in the TESS photometry, calculated the most probable period aliases based on these data, and then scheduled CHEOPS observations. The photometric data were supplemented with ESPRESSO (Echelle SPectrograph for Rocky Exoplanets and Stable Spectroscopic Observations) radial velocity data. Finally, a combined model was fitted to the entire dataset in order to obtain final planetary and system parameters. Results. Based on the combined TESS and CHEOPS observations, we successfully determined the true orbital period of the planet d to be 47.42489 ± 0.00011 days, and derived precise radii of the planets in the system, namely 1.362 ± 0.040 R, 2.328 ± 0.039 R, and 2.607 ± 0.060 R for planets b, c, and d, respectively. Due to the low number of radial velocities, we were only able to determine 3σ upper limits for these respective planet masses, which are 13.71 M, 9.72 M, and 26.57 M. We estimated that another 48 ESPRESSO radial velocities are needed to measure the predicted masses of all planets in HD 22946. We also derived stellar parameters for the host star. Conclusions. Planet c around HD 22946 appears to be a promising target for future atmospheric characterisation via transmission spectroscopy. We can also conclude that planet d, as a warm sub-Neptune, is very interesting because there are only a few similar confirmed exoplanets to date. Such objects are worth investigating in the near future, for example in terms of their composition and internal structure.
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| 47. |
- Grabner, B, et al.
(författare)
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Disruption of STAT3 signalling promotes KRAS-induced lung tumorigenesis
- 2015
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6, s. 6285-
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Tidskriftsartikel (refereegranskat)abstract
- STAT3 is considered to play an oncogenic role in several malignancies including lung cancer; consequently, targeting STAT3 is currently proposed as therapeutic intervention. Here we demonstrate that STAT3 plays an unexpected tumour-suppressive role in KRAS mutant lung adenocarcinoma (AC). Indeed, lung tissue-specific inactivation of Stat3 in mice results in increased KrasG12D-driven AC initiation and malignant progression leading to markedly reduced survival. Knockdown of STAT3 in xenografted human AC cells increases tumour growth. Clinically, low STAT3 expression levels correlate with poor survival and advanced malignancy in human lung AC patients with smoking history, which are prone to KRAS mutations. Consistently, KRAS mutant lung tumours exhibit reduced STAT3 levels. Mechanistically, we demonstrate that STAT3 controls NF-κB-induced IL-8 expression by sequestering NF-κB within the cytoplasm, thereby inhibiting IL-8-mediated myeloid tumour infiltration and tumour vascularization and hence tumour progression. These results elucidate a novel STAT3–NF-κB–IL-8 axis in KRAS mutant AC with therapeutic and prognostic relevance.
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| 48. |
- Hobson, Melissa J., et al.
(författare)
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TOI-199 b : A Well-characterized 100 day Transiting Warm Giant Planet with TTVs Seen from Antarctica
- 2023
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Ingår i: Astronomical Journal. - 0004-6256. ; 166:5
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Tidskriftsartikel (refereegranskat)abstract
- We present the spectroscopic confirmation and precise mass measurement of the warm giant planet TOI-199 b. This planet was first identified in TESS photometry and confirmed using ground-based photometry from ASTEP in Antarctica including a full 6.5 hr long transit, PEST, Hazelwood, and LCO; space photometry from NEOSSat; and radial velocities (RVs) from FEROS, HARPS, CORALIE, and CHIRON. Orbiting a late G-type star, TOI-199 b has a 104.854 − 0.002 + 0.001 day period, a mass of 0.17 ± 0.02 M J, and a radius of 0.810 ± 0.005 R J. It is the first warm exo-Saturn with a precisely determined mass and radius. The TESS and ASTEP transits show strong transit timing variations (TTVs), pointing to the existence of a second planet in the system. The joint analysis of the RVs and TTVs provides a unique solution for the nontransiting companion TOI-199 c, which has a period of 273.69 − 0.22 + 0.26 days and an estimated mass of 0.28 − 0.01 + 0.02 M J . This period places it within the conservative habitable zone.
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