| 1. |
- Acharya, B. S., et al.
(författare)
-
Introducing the CTA concept
- 2013
-
Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 43, s. 3-18
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project. (C) 2013 Elsevier B.V. All rights reserved.
|
|
| 2. |
- Mishra, A., et al.
(författare)
-
Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
-
Tidskriftsartikel (refereegranskat)abstract
- Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
|
|
| 3. |
|
|
| 4. |
- Lopez-Soley, E, et al.
(författare)
-
Dynamics and Predictors of Cognitive Impairment along the Disease Course in Multiple Sclerosis
- 2021
-
Ingår i: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 11:11
-
Tidskriftsartikel (refereegranskat)abstract
- (1) Background: The evolution and predictors of cognitive impairment (CI) in multiple sclerosis (MS) are poorly understood. We aimed to define the temporal dynamics of cognition throughout the disease course and identify clinical and neuroimaging measures that predict CI. (2) Methods: This paper features a longitudinal study with 212 patients who underwent several cognitive examinations at different time points. Dynamics of cognition were assessed using mixed-effects linear spline models. Machine learning techniques were used to identify which baseline demographic, clinical, and neuroimaging measures best predicted CI. (3) Results: In the first 5 years of MS, we detected an increase in the z-scores of global cognition, verbal memory, and information processing speed, which was followed by a decline in global cognition and memory (p < 0.05) between years 5 and 15. From 15 to 30 years of disease onset, cognitive decline continued, affecting global cognition and verbal memory. The baseline measures that best predicted CI were education, disease severity, lesion burden, and hippocampus and anterior cingulate cortex volume. (4) Conclusions: In MS, cognition deteriorates 5 years after disease onset, declining steadily over the next 25 years and more markedly affecting verbal memory. Education, disease severity, lesion burden, and volume of limbic structures predict future CI and may be helpful when identifying at-risk patients.
|
|
| 5. |
- Lopez-Soley, E, et al.
(författare)
-
Diffusion tensor imaging metrics associated with future disability in multiple sclerosis
- 2023
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 13:1, s. 3565-
-
Tidskriftsartikel (refereegranskat)abstract
- The relationship between brain diffusion microstructural changes and disability in multiple sclerosis (MS) remains poorly understood. We aimed to explore the predictive value of microstructural properties in white (WM) and grey matter (GM), and identify areas associated with mid-term disability in MS patients. We studied 185 patients (71% female; 86% RRMS) with the Expanded Disability Status Scale (EDSS), timed 25-foot walk (T25FW), nine-hole peg test (9HPT), and Symbol Digit Modalities Test (SDMT) at two time-points. We used Lasso regression to analyse the predictive value of baseline WM fractional anisotropy and GM mean diffusivity, and to identify areas related to each outcome at 4.1 years follow-up. Motor performance was associated with WM (T25FW: RMSE = 0.524, R2 = 0.304; 9HPT dominant hand: RMSE = 0.662, R2 = 0.062; 9HPT non-dominant hand: RMSE = 0.649, R2 = 0.139), and SDMT with GM diffusion metrics (RMSE = 0.772, R2 = 0.186). Cingulum, longitudinal fasciculus, optic radiation, forceps minor and frontal aslant were the WM tracts most closely linked to motor dysfunction, and temporal and frontal cortex were relevant for cognition. Regional specificity related to clinical outcomes provide valuable information that can be used to develop more accurate predictive models that could improve therapeutic strategies.
|
|
| 6. |
- Solana, E, et al.
(författare)
-
Regional grey matter microstructural changes and volume loss according to disease duration in multiple sclerosis patients
- 2021
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 16805-
-
Tidskriftsartikel (refereegranskat)abstract
- The spatio-temporal characteristics of grey matter (GM) impairment in multiple sclerosis (MS) are poorly understood. We used a new surface-based diffusion MRI processing tool to investigate regional modifications of microstructure, and we quantified volume loss in GM in a cohort of patients with MS classified into three groups according to disease duration. Additionally, we investigated the relationship between GM changes with disease severity. We studied 54 healthy controls and 247 MS patients classified regarding disease duration: MS1 (less than 5 years, n = 67); MS2 (5–15 years, n = 107); and MS3 (more than15 years, n = 73). We compared GM mean diffusivity (MD), fractional anisotropy (FA) and volume between groups, and estimated their clinical associations. Regional modifications in diffusion measures (MD and FA) and volume did not overlap early in the disease, and became widespread in later phases. We found higher MD in MS1 group, mainly in the temporal cortex, and volume reduction in deep GM and left precuneus. Additional MD changes were evident in cingulate and occipital cortices in the MS2 group, coupled to volume reductions in deep GM and parietal and frontal poles. Changes in MD and volume extended to more than 80% of regions in MS3 group. Conversely, increments in FA, with very low effect size, were observed in the parietal cortex and thalamus in MS1 and MS2 groups, and extended to the frontal lobe in the later group. MD and GM changes were associated with white matter lesion load and with physical and cognitive disability. Microstructural integrity loss and atrophy present differential spatial predominance early in MS and accrual over time, probably due to distinct pathogenic mechanisms that underlie tissue damage.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Muino, E., et al.
(författare)
-
RP11-362K2.2:RP11-767I20.1 Genetic Variation Is Associated with Post-Reperfusion Therapy Parenchymal Hematoma. A GWAS Meta-Analysis
- 2021
-
Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 10:14
-
Tidskriftsartikel (refereegranskat)abstract
- Stroke is one of the most common causes of death and disability. Reperfusion therapies are the only treatment available during the acute phase of stroke. Due to recent clinical trials, these therapies may increase their frequency of use by extending the time-window administration, which may lead to an increase in complications such as hemorrhagic transformation, with parenchymal hematoma (PH) being the more severe subtype, associated with higher mortality and disability rates. Our aim was to find genetic risk factors associated with PH, as that could provide molecular targets/pathways for their prevention/treatment and study its genetic correlations to find traits sharing genetic background. We performed a GWAS and meta-analysis, following standard quality controls and association analysis (fastGWAS), adjusting age, NIHSS, and principal components. FUMA was used to annotate, prioritize, visualize, and interpret the meta-analysis results. The total number of patients in the meta-analysis was 2034 (216 cases and 1818 controls). We found rs79770152 having a genome-wide significant association (beta 0.09, p-value 3.90 x 10(-8)) located in the RP11-362K2.2:RP11-767I20.1 gene and a suggestive variant (rs13297983: beta 0.07, p-value 6.10 x 10(-8)) located in PCSK5 associated with PH occurrence. The genetic correlation showed a shared genetic background of PH with Alzheimer's disease and white matter hyperintensities. In addition, genes containing the ten most significant associations have been related to aggregated amyloid-beta, tau protein, white matter microstructure, inflammation, and matrix metalloproteinases.
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Eiroa, C., et al.
(författare)
-
Cold DUst around NEarby Stars (DUNES). First results A resolved exo-Kuiper belt around the solar-like star zeta(2) Ret
- 2010
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L131-
-
Tidskriftsartikel (refereegranskat)abstract
- We present the first far-IR observations of the solar-type stars delta Pav, HR 8501, 51 Peg and zeta(2) Ret, taken within the context of the DUNES Herschel open time key programme (OTKP). This project uses the PACS and SPIRE instruments with the objective of studying infrared excesses due to exo-Kuiper belts around nearby solar-type stars. The observed 100 mu m fluxes from delta Pav, HR 8501, and 51 Peg agree with the predicted photospheric fluxes, excluding debris disks brighter than L-dust/L-star similar to 5 x 10(-7) (1 sigma level) around those stars. A flattened, disk-like structure with a semi-major axis of similar to 100 AU in size is detected around zeta(2) Ret. The resolved structure suggests the presence of an eccentric dust ring, which we interpret as an exo-Kuiper belt with L-dust/L-star approximate to 10(-5).
|
|
| 15. |
- Eiroa, C., et al.
(författare)
-
DUst around NEarby Stars. The survey observational results
- 2013
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 555, s. A11-
-
Tidskriftsartikel (refereegranskat)abstract
- Context. Debris discs are a consequence of the planet formation process and constitute the fingerprints of planetesimal systems. Their solar system counterparts are the asteroid and Edgeworth-Kuiper belts. Aims. The DUNES survey aims at detecting extra-solar analogues to the Edgeworth-Kuiper belt around solar-type stars, putting in this way the solar system into context. The survey allows us to address some questions related to the prevalence and properties of planetesimal systems. Methods. We used Herschel/PACS to observe a sample of nearby FGK stars. Data at 100 and 160 mu m were obtained, complemented in some cases with observations at 70 mu m, and at 250, 350 and 500 mu m using SPIRE. The observing strategy was to integrate as deep as possible at 100 mu m to detect the stellar photosphere. Results. Debris discs have been detected at a fractional luminosity level down to several times that of the Edgeworth-Kuiper belt. The incidence rate of discs around the DUNES stars is increased from a rate of similar to 12.1% +/- 5% before Herschel to similar to 20.2% +/- 2%. A significant fraction (similar to 52%) of the discs are resolved, which represents an enormous step ahead from the previously known resolved discs. Some stars are associated with faint far-IR excesses attributed to a new class of cold discs. Although it cannot be excluded that these excesses are produced by coincidental alignment of background galaxies, statistical arguments suggest that at least some of them are true debris discs. Some discs display peculiar SEDs with spectral indexes in the 70-160 mu m range steeper than the Rayleigh-Jeans one. An analysis of the debris disc parameters suggests that a decrease might exist of the mean black body radius from the F-type to the K-type stars. In addition, a weak trend is suggested for a correlation of disc sizes and an anticorrelation of disc temperatures with the stellar age.
|
|
| 16. |
- Carsin, A. E., et al.
(författare)
-
Spirometric patterns in young and middle-aged adults: a 20-year European study
- 2024
-
Ingår i: Thorax. - : BMJ Publishing Group Ltd. - 0040-6376 .- 1468-3296. ; 79:2, s. 153-162
-
Tidskriftsartikel (refereegranskat)abstract
- Background Understanding the natural history of abnormal spirometric patterns at different stages of life is critical to identify and optimise preventive strategies. We aimed to describe characteristics and risk factors of restrictive and obstructive spirometric patterns occurring before 40 years (young onset) and between 40 and 61 years (mid-adult onset). Methods We used data from the population- based cohort of the European Community Respiratory Health Survey (ECRHS). Prebronchodilator forced expiratory volume in one second (FEV 1) and forced vital capacity (FVC) were assessed longitudinally at baseline (ECRHS1, 1993-1994) and again 20 years later ( ECRHS3, 2010-2013). Spirometry patterns were defined as: restrictive if FEV1/ FVC >= LLN and FVC<10th percentile, obstructive if FEV1/FVC
|
|
