| 1. |
- Cruz, Raquel, et al.
(författare)
-
Novel genes and sex differences in COVID-19 severity
- 2022
-
Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
-
Tidskriftsartikel (refereegranskat)abstract
- Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
|
|
| 2. |
-
- 2019
-
Tidskriftsartikel (refereegranskat)
|
|
| 3. |
- Abdellaoui, G., et al.
(författare)
-
First observations of speed of light tracks by a fluorescence detector looking down on the atmosphere
- 2018
-
Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- EUSO-Balloon is a pathfinder mission for the Extreme Universe Space Observatory onboard the Japanese Experiment Module (JEM-EUSO). It was launched on the moonless night of the 25(th) of August 2014 from Timmins, Canada. The flight ended successfully after maintaining the target altitude of 38 km for five hours. One part of the mission was a 2.5 hour underflight using a helicopter equipped with three UV light sources (LED, xenon flasher and laser) to perform an inflight calibration and examine the detectors capability to measure tracks moving at the speed of light. We describe the helicopter laser system and details of the underflight as well as how the laser tracks were recorded and found in the data. These are the first recorded laser tracks measured from a fluorescence detector looking down on the atmosphere. Finally, we present a first reconstruction of the direction of the laser tracks relative to the detector.
|
|
| 4. |
- Abdellaoui, G., et al.
(författare)
-
Meteor studies in the framework of the JEM-EUSO program
- 2017
-
Ingår i: Planetary and Space Science. - : Elsevier. - 0032-0633 .- 1873-5088. ; 143, s. 245-255
-
Tidskriftsartikel (refereegranskat)abstract
- We summarize the state of the art of a program of UV observations from space of meteor phenomena, a secondary objective of the JEM-EUSO international collaboration. Our preliminary analysis indicates that JEM-EUSO, taking advantage of its large FOV and good sensitivity, should be able to detect meteors down to absolute magnitude close to 7. This means that JEM-EUSO should be able to record a statistically significant flux of meteors, including both sporadic ones, and events produced by different meteor streams. Being unaffected by adverse weather conditions, JEM-EUSO can also be a very important facility for the detection of bright meteors and fireballs, as these events can be detected even in conditions of very high sky background. In the case of bright events, moreover, exhibiting some persistence of the meteor train, preliminary simulations show that it should be possible to exploit the motion of the ISS itself and derive at least a rough 3D reconstruction of the meteor trajectory. Moreover, the observing strategy developed to detect meteors may also be applied to the detection of nuclearites, exotic particles whose existence has been suggested by some theoretical investigations. Nuclearites are expected to move at higher velocities than meteoroids, and to exhibit a wider range of possible trajectories, including particles moving upward after crossing the Earth. Some pilot studies, including the approved Mini-EUSO mission, a precursor of JEM-EUSO, are currently operational or in preparation. We are doing simulations to assess the performance of Mini-EUSO for meteor studies, while a few meteor events have been already detected using the ground-based facility EUSO-TA.
|
|
| 5. |
- Alex-Amor, Antonio, et al.
(författare)
-
Elliptical Glide-Symmetric Holey Metasurfaces for Wideband Anisotropy
- 2020
-
Ingår i: 2020 14th European Conference on Antennas and Propagation (EUCAP 2020). - : Institute of Electrical and Electronics Engineers (IEEE).
-
Konferensbidrag (refereegranskat)abstract
- This paper presents a mode-matching technique to study the dispersive features of periodic structures composed of glide-symmetric elliptical holes. As a difference from purely numerical methods, our formulation provides physical insight on the Floquet harmonics. At the same time, the computational cost is reduced compared to general purpose commercial software. The fields inside the holes are described by means of Mathieu functions and subsequently used to compute the full 2-D dispersion diagrams. With the presented analysis, we demonstrate that glide-symmetric periodic structures with elliptical holes offer anisotropic refractive indexes over a wide range of frequencies.
|
|
| 6. |
- Alex-Amor, Antonio, et al.
(författare)
-
Glide-Symmetric Metallic Structures With Elliptical Holes for Lens Compression
- 2020
-
Ingår i: IEEE transactions on microwave theory and techniques. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9480 .- 1557-9670. ; 68:10, s. 4236-4248
-
Tidskriftsartikel (refereegranskat)abstract
- In this article, we study the wave propagation in a metallic parallel-plate structure with glide-symmetric elliptical holes. To perform this study, we derived a mode-matching technique based on the generalized Floquet theorem for glide-symmetric structures. This mode-matching technique benefits from a lower computational cost since it takes advantage of the glide symmetry in the structure. It also provides physical insight into the specific properties of Floquet modes propagating in these specific structures. With our analysis, we demonstrate that glide-symmetric structures with periodic elliptical holes exhibit an anisotropic refractive index over a wide range of frequencies. The equivalent refractive index can be controlled by tuning the dimensions of the holes. Finally, by combining the anisotropy related to the elliptical holes and transformation optics, a Maxwell fish-eye (MFL) lens with a 33.33% size compression is designed. This lens operates in a wideband frequency range from 2.5 to 10 GHz.
|
|
| 7. |
- Alex-Amor, Antonio, et al.
(författare)
-
Wave Propagation in Periodic Metallic Structures with Equilateral Triangular Holes
- 2020
-
Ingår i: Applied Sciences. - : MDPI. - 2076-3417. ; 10:5
-
Tidskriftsartikel (refereegranskat)abstract
- This paper studies wave propagation in a periodic parallel-plate waveguide with equilateral triangular holes. A mode-matching method is implemented to analyze the dispersion diagram of the structure possessing glide and mirror symmetries. Both structures present an unexpected high degree of isotropy, despite the triangle not being symmetric with respect to rotations of 90 degrees. We give some physical insight on the matter by carrying out a modal decomposition of the total field on the hole and identifying the most significant modes. Additionally, we demonstrate that the electrical size of the triangular hole plays a fundamental role in the physical mechanism that causes that isotropic behavior. Finally, we characterize the influence of the different geometrical parameters that conform the unit cell (period, triangle size, hole depth, separation between metallic plates). The glide-symmetric configuration offers higher equivalent refractive indexes and widens the stopband compared to the mirror-symmetric configuration. We show that the stopband is wider as the triangle size is bigger, unlike holey structures composed of circular and elliptical holes where an optimal hole size exists.
|
|
| 8. |
- Artiach, Gonzalo, et al.
(författare)
-
Omega-3 Polyunsaturated Fatty Acids Decrease Aortic Valve Disease through the Resolvin E1 and ChemR23 Axis.
- 2020
-
Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 142, s. 776-789
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Aortic valve stenosis (AVS), which is the most common valvular heart disease, causes a progressive narrowing of the aortic valve as a consequence of thickening and calcification of the aortic valve leaflets. The beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) in cardiovascular prevention have been recently demonstrated in a large randomized controlled trial. In addition, n-3 PUFA serve as the substrate for the synthesis of specialized pro-resolving mediators (SPMs), which are known by their potent beneficial anti-inflammatory, pro-resolving and tissue-modifying properties in cardiovascular disease. However, the effects of n-3 PUFA and SPMs on AVS have not yet been determined. The aim of this study was to identify the role of n-3 PUFA-derived SPMs in relation to the development of AVS. Methods: Lipidomic and transcriptomic analyses were performed in human tricuspid aortic valves. Apoe-/- mice and wire injury in C57BL/6J mice were used as models for mechanistic studies. Results: We found that n-3 PUFA incorporation into human stenotic aortic valves was higher in non-calcified regions compared with calcified regions. LC-MS-MS based lipid mediator lipidomics identified that the n-3 PUFA-derived SPM resolvin E1 (RvE1) was dysregulated in calcified regions and acted as a calcification inhibitor. Apoe-/- mice expressing the Caenorhabditis elegans Fat-1 transgene (Fat-1tgxApoe-/-), which enables the endogenous synthesis of n-3 PUFA, increased valvular n-3 PUFA content, exhibited reduced valve calcification, lower aortic valve leaflet area, increased M2 macrophage polarization and improved echocardiographic parameters. Finally, abrogation of the RvE1 receptor ChemR23 enhanced disease progression, and the beneficial effects of Fat-1tg were abolished in the absence of ChemR23. Conclusions: n-3 PUFA-derived RvE1 and its receptor ChemR23 emerge as a key axis in the inhibition of AVS progression, and may represent a novel potential therapeutic opportunity to be evaluated in patients with AVS.
|
|
| 9. |
- Ayala, Alba, et al.
(författare)
-
Influence of Active and Healthy Ageing on Quality of Life Changes : Insights from the Comparison of Three European Countries
- 2021
-
Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 18:8
-
Tidskriftsartikel (refereegranskat)abstract
- This study aimed to analyze the determinants of quality of life (QoL) in older people in three European countries (Portugal, Spain and Sweden). A sample of 7589 participants in waves 4 (2011) and 6 (2015) of the Survey on Health, Aging, and Retirement in Europe (SHARE) project, aged 50 and over and living in Portugal, Spain and Sweden, was included. The CASP-12 scale was used to measure QoL. A principal component analysis was performed to group preselected variables related to active and healthy ageing into the dimensions of health, social participation, and lifelong learning. A linear regression model was built using the change in CASP-12 scores over the 4-year follow-up as the dependent variable, including the interactions between country and each independent variable in the model. After four years, the average QoL increased in Portugal (difference = 0.8, p < 0.001), decreased in Spain (-0.8, p < 0.001), and remained constant in Sweden (0.1, p = 0.408). A significant country-participation component interaction (p = 0.039) was found. In Spain, a higher participation (beta = 0.031, p = 0.002) was related to a higher QoL improvement at 4 years, but not in Sweden or Portugal. Physical health and emotional components (beta = 0.099, p < 0.001), functional ability (beta = 0.044, p = 0.023), and cognitive and sensory ability (beta = 0.021, p = 0.026) were associated with QoL changes over time in all countries. The country-specific associations between health, social participation and QoL should be taken into account when developing public health policies to promote QoL among European older people.
|
|
| 10. |
- Bentham, James, et al.
(författare)
-
A century of trends in adult human height
- 2016
-
Ingår i: eLIFE. - 2050-084X. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
|
|
| 11. |
- Bentham, James, et al.
(författare)
-
A century of trends in adult human height
- 2016
-
Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
|
|
| 12. |
- Beridze, Giorgi, et al.
(författare)
-
Are Loneliness and Social Isolation Associated with Quality of Life in Older Adults? Insights from Northern and Southern Europe
- 2020
-
Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 17:22
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Loneliness and social isolation have detrimental effects on health in old age; however, the prospective associations with quality of life (QoL) remain unclear. Furthermore, despite the existence of a European north-south gradient in the distribution of loneliness and social isolation, little is known whether the associations are context-specific. We investigated the relationships between loneliness, social isolation and QoL of older adults residing in the North (Sweden) and South (Spain) of Europe. Methods: Study sample consisted of 2995 Swedish and 4154 Spanish older adults who participated in waves six and seven of the Study on Health, Aging and Retirement in Europe (SHARE). Loneliness and social isolation were measured at the baseline, and QoL was measured at the baseline and follow-up using CASP-12. Prospective associations were assessed via multivariate linear regression. Results: In Sweden, subjects with higher vs. lower loneliness had 1.01 (95% CI: -1.55, -0.40) units lower QoL, while every standard deviation increase in social isolation was associated with a 0.27 (95% CI: -0.42, -0.09)-unit decrease in QoL. In Spain, every standard deviation increase in social isolation was associated with a 0.66 (95% CI: -1.11, -0.22)-unit decrease in QoL. The association was stronger in subjects aged <= 65 years old and those with no chronic diseases. The association with loneliness was not statistically significant in Spain. Conclusion: Loneliness and social isolation are prospectively associated with decreased QoL among older adults, yet the associations are contextually bound. Future interventions should target both exposures, among others, in order to increase QoL in this group.
|
|
| 13. |
- Castillo Tapia, Pilar, et al.
(författare)
-
Ray-Tracing Model for the Design and Efficiency Calculation of a Monolithic Geodesic Lens Array Antenna
- 2024
-
Ingår i: 18th European Conference on Antennas and Propagation, EuCAP 2024. - : Institute of Electrical and Electronics Engineers (IEEE).
-
Konferensbidrag (refereegranskat)abstract
- We propose the use of a generalized ray-tracing model to design geodesic lens array antennas. This model is capable of computing the radiation patterns and taking into account losses due to finite conductivity and surface roughness, which are essential when producing prototypes as single monolithic pieces. The ray-tracing model is used to design a modified Rinehart-Luneburg lens that shows very good agreement with simulations while significantly decreasing computation time. The profile of the lens is designed in such a way that it can be vertically stacked in an array and produced as a single piece. The lens array antenna is manufactured as a single monolithic piece using the laser powder-bed fusion technique. The tests of this prototype validate the use of additive manufacturing for geodesic lens antennas operating in V-band.
|
|
| 14. |
- Castillo Tapia, Pilar, et al.
(författare)
-
V-Band Monolithic Additive-Manufactured Geodesic Lens Array Antenna
- 2023
-
Ingår i: IEEE Antennas and Wireless Propagation Letters. - : Institute of Electrical and Electronics Engineers (IEEE). - 1536-1225 .- 1548-5757. ; 22:10, s. 2527-2531
-
Tidskriftsartikel (refereegranskat)abstract
- Fully metallic geodesic lens antennas are popular for millimeter-wave band applications due to their simplicity, robustness, and low loss. Here, we report the experimental results of a geodesic lens array antenna, which was specifically designed to be additive-manufactured in one single piece using laser powder-bed fusion (LPBF). LPBF in aluminum alloy AlSi10Mg is able to produce high conductivity and relatively low surface roughness, so the antenna is highly directive and efficient. In addition, LPBF increases the robustness of the design since the lens array is monolithic, i.e., the risks associated with the assembly, including misalignments and undesired air gaps between pieces, are totally eliminated.
|
|
| 15. |
- Clendinning, Sarah, et al.
(författare)
-
Tailoring the Performance of Geodesic Lens Antennas By Defining their Footprint
- 2024
-
Ingår i: 18th European Conference on Antennas and Propagation, EuCAP 2024. - : Institute of Electrical and Electronics Engineers (IEEE).
-
Konferensbidrag (refereegranskat)abstract
- This paper discusses non-rotationally symmetric geodesic lens antennas. By defining the shape of the lens footprint, additional degrees of freedom are introduced into the design process, allowing for further tailoring of the electromagnetic performance of the lens while simultaneously reducing the volume occupied by the lens. An in-house ray-tracing model for geodesic lenses has been modified to analyze this class of lenses. Examples showing the effect of modifying the lens profile are presented, with a more detailed discussion on profile presenting improved side-lobe levels at the extreme ports. The examples presented operate at 30 GHz.
|
|
| 16. |
- Corman, Alba, et al.
(författare)
-
A chemical screen for modulators of mRNA translation identifies a distinct mechanism of toxicity for sphingosine kinase inhibitors
- 2021
-
Ingår i: PLoS biology. - : Public library of science. - 1544-9173 .- 1545-7885. ; 19:5
-
Tidskriftsartikel (refereegranskat)abstract
- We here conducted an image-based chemical screen to evaluate how medically approved drugs, as well as drugs that are currently under development, influence overall translation levels. None of the compounds up-regulated translation, which could be due to the screen being performed in cancer cells grown in full media where translation is already present at very high levels. Regarding translation down-regulators, and consistent with current knowledge, inhibitors of the mechanistic target of rapamycin (mTOR) signaling pathway were the most represented class. In addition, we identified that inhibitors of sphingosine kinases (SPHKs) also reduce mRNA translation levels independently of mTOR. Mechanistically, this is explained by an effect of the compounds on the membranes of the endoplasmic reticulum (ER), which activates the integrated stress response (ISR) and contributes to the toxicity of SPHK inhibitors. Surprisingly, the toxicity and activation of the ISR triggered by 2 independent SPHK inhibitors, SKI-II and ABC294640, the latter in clinical trials, are also observed in cells lacking SPHK1 and SPHK2. In summary, our study provides a useful resource on the effects of medically used drugs on translation, identified compounds capable of reducing translation independently of mTOR and has revealed that the cytotoxic properties of SPHK inhibitors being developed as anticancer agents are independent of SPHKs.
|
|
| 17. |
- Danaei, Goodarz, et al.
(författare)
-
Effects of diabetes definition on global surveillance of diabetes prevalence and diagnosis: a pooled analysis of 96 population-based studies with 331288 participants
- 2015
-
Ingår i: The Lancet Diabetes & Endocrinology. - 2213-8595 .- 2213-8587. ; 3:8, s. 624-637
-
Tidskriftsartikel (refereegranskat)abstract
- Background Diabetes has been defined on the basis of different biomarkers, including fasting plasma glucose (FPG), 2-h plasma glucose in an oral glucose tolerance test (2hOGTT), and HbA(1c). We assessed the effect of different diagnostic definitions on both the population prevalence of diabetes and the classification of previously undiagnosed individuals as having diabetes versus not having diabetes in a pooled analysis of data from population-based health examination surveys in different regions. Methods We used data from 96 population-based health examination surveys that had measured at least two of the biomarkers used for defining diabetes. Diabetes was defined using HbA(1c) (HbA(1c) >= 6 . 5% or history of diabetes diagnosis or using insulin or oral hypoglycaemic drugs) compared with either FPG only or FPG-or-2hOGTT definitions (FPG >= 7 . 0 mmol/L or 2hOGTT >= 11 . 1 mmol/L or history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated diabetes prevalence, taking into account complex survey design and survey sample weights. We compared the prevalences of diabetes using different definitions graphically and by regression analyses. We calculated sensitivity and specificity of diabetes diagnosis based on HbA1c compared with diagnosis based on glucose among previously undiagnosed individuals (ie, excluding those with history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated sensitivity and specificity in each survey, and then pooled results using a random-effects model. We assessed the sources of heterogeneity of sensitivity by meta-regressions for study characteristics selected a priori. Findings Population prevalence of diabetes based on FPG- or-2hOGTT was correlated with prevalence based on FPG alone (r= 0 . 98), but was higher by 2-6 percentage points at different prevalence levels. Prevalence based on HbA(1c) was lower than prevalence based on FPG in 42 . 8% of age-sex-survey groups and higher in another 41 . 6%; in the other 15 . 6%, the two definitions provided similar prevalence estimates. The variation across studies in the relation between glucose-based and HbA(1c)-based prevalences was partly related to participants' age, followed by natural logarithm of per person gross domestic product, the year of survey, mean BMI, and whether the survey population was national, subnational, or from specific communities. Diabetes defined as HbA(1c) 6 . 5% or more had a pooled sensitivity of 52 . 8% (95% CI 51 . 3-54 . 3%) and a pooled specificity of 99 . 74% (99 . 71-99 . 78%) compared with FPG 7 . 0 mmol/L or more for diagnosing previously undiagnosed participants; sensitivity compared with diabetes defined based on FPG-or-2hOGTT was 30 . 5% (28 . 7-32 . 3%). None of the preselected study-level characteristics explained the heterogeneity in the sensitivity of HbA(1c) versus FPG. Interpretation Different biomarkers and definitions for diabetes can provide different estimates of population prevalence of diabetes, and differentially identify people without previous diagnosis as having diabetes. Using an HbA(1c)-based definition alone in health surveys will not identify a substantial proportion of previously undiagnosed people who would be considered as having diabetes using a glucose-based test.
|
|
| 18. |
- Deming, Yuetiva, et al.
(författare)
-
Genome-wide association study identifies four novel loci associated with Alzheimer’s endophenotypes and disease modifiers
- 2017
-
Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 133:5, s. 839-856
-
Tidskriftsartikel (refereegranskat)abstract
- More than 20 genetic loci have been associated with risk for Alzheimer’s disease (AD), but reported genome-wide significant loci do not account for all the estimated heritability and provide little information about underlying biological mechanisms. Genetic studies using intermediate quantitative traits such as biomarkers, or endophenotypes, benefit from increased statistical power to identify variants that may not pass the stringent multiple test correction in case–control studies. Endophenotypes also contain additional information helpful for identifying variants and genes associated with other aspects of disease, such as rate of progression or onset, and provide context to interpret the results from genome-wide association studies (GWAS). We conducted GWAS of amyloid beta (Aβ42), tau, and phosphorylated tau (ptau181) levels in cerebrospinal fluid (CSF) from 3146 participants across nine studies to identify novel variants associated with AD. Five genome-wide significant loci (two novel) were associated with ptau181, including loci that have also been associated with AD risk or brain-related phenotypes. Two novel loci associated with Aβ42 near GLIS1 on 1p32.3 (β = −0.059, P = 2.08 × 10−8) and within SERPINB1 on 6p25 (β = −0.025, P = 1.72 × 10−8) were also associated with AD risk (GLIS1: OR = 1.105, P = 3.43 × 10−2), disease progression (GLIS1: β = 0.277, P = 1.92 × 10−2), and age at onset (SERPINB1: β = 0.043, P = 4.62 × 10−3). Bioinformatics indicate that the intronic SERPINB1 variant (rs316341) affects expression of SERPINB1 in various tissues, including the hippocampus, suggesting that SERPINB1 influences AD through an Aβ-associated mechanism. Analyses of known AD risk loci suggest CLU and FERMT2 may influence CSF Aβ42 (P = 0.001 and P = 0.009, respectively) and the INPP5D locus may affect ptau181 levels (P = 0.009); larger studies are necessary to verify these results. Together the findings from this study can be used to inform future AD studies.
|
|
| 19. |
|
|
| 20. |
- Fabian, ID, et al.
(författare)
-
Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European countries
- 2021
-
Ingår i: The British journal of ophthalmology. - : BMJ. - 1468-2079 .- 0007-1161. ; 105:10, s. 1435-1443
-
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.
|
|
| 21. |
- Faccio, Ricardo, et al.
(författare)
-
Electronic and Structural Distortions in Graphene Induced by Carbon Vacancies and Boron Doping
- 2010
-
Ingår i: JOURNAL OF PHYSICAL CHEMISTRY C. - : American Chemical Society. - 1932-7447 .- 1932-7455. ; 114:44, s. 18961-18971
-
Tidskriftsartikel (refereegranskat)abstract
- We present an ab initio-DFT/GGA-study on the structural and electronic distortions of modified graphene by the creation of vacancies, the inclusion of boron atoms, and the coexistence of both, by means of total energy and band structure calculations. In the case of coexistence of boron atoms and vacancy, the modified grapheme presents spin polarization only when B atoms locate far from vacancy. Thus, when a boron atom fills single and divacancies, it suppresses the spin polarization of the charge density. In particular, when B atoms fill a divacancy, a new type of rearrangement occurs, where a stable BC4 unit is formed inducing important out-of-plane distortions to graphene. All these findings suggest that new chemical modifications to grapheme and new types of vacancies can be used to modify its electronic properties.
|
|
| 22. |
- Fernández-de-las-Peñas, César, et al.
(författare)
-
Serological Biomarkers at Hospital Admission and Hospitalization Treatments Are Not Related to Sensitization-Associated Symptoms in Patients with Post-COVID Pain
- 2023
-
Ingår i: Pathogens. - 2076-0817. ; 12:10
-
Tidskriftsartikel (refereegranskat)abstract
- Current evidence suggests that a group of patients who had survived coronavirus disease, 2019 (COVID-19) and developed post-COVID pain can exhibit altered nociceptive processing. The role of serological biomarkers and hospitalization treatments in post-COVID pain is unclear. This study aimed to investigate the association of serological biomarkers and treatments received during hospitalization with sensitization-associated symptoms in COVID-19 survivors with post-COVID pain. One hundred and eighty-three (n = 183) patients who had been hospitalized due to COVID-19 in one urban hospital of Madrid (Spain) during the first wave of the pandemic were assessed in a face-to-face interview 9.4 (SD 3.4) months after hospitalization. Levels of 19 serological biomarkers, hospitalization data, and treatments during hospitalization were obtained from hospital records. Sensitization-associated symptoms (Central Sensitization Inventory, CSI), sleep quality (Pittsburgh Sleep Quality Index, PSQI), pain catastrophism (Pain Catastrophizing Scale), and anxiety/depressive level (Hospital Anxiety and Depression Scale, HADS) were assessed. The prevalence of post-COVID pain was 40.9% (n = 75). Twenty-nine (38.6%) patients had sensitization-associated symptoms. Overall, no differences in hospitalization data and serological biomarkers were identified according to the presence of sensitization-associated symptoms. The analysis revealed that patients with sensitization-associated symptoms exhibited higher lymphocyte count and lower urea levels than those without sensitization-associated symptoms, but differences were small. Pain catastrophism and depressive levels, but not fatigue, dyspnea, brain fog, anxiety levels, or poor sleep, were higher in individuals with sensitization-associated symptoms. In conclusion, this study revealed that sensitization-associated post-COVID pain symptoms are not associated with serological biomarkers at hospital admission and hospitalization treatments received.
|
|
| 23. |
- Fernandez-Prieto, Armando, et al.
(författare)
-
Glide Symmetry Applied to the Design of Common-Mode Rejection Filters Based on Complementary Split-Ring Resonators
- 2023
-
Ingår i: IEEE Transactions on Circuits and Systems - II - Express Briefs. - : Institute of Electrical and Electronics Engineers (IEEE). - 1549-7747 .- 1558-3791. ; 70:6, s. 1911-1915
-
Tidskriftsartikel (refereegranskat)abstract
- In this brief, glide symmetry is applied to design common-mode rejection filters based on defected ground structures with bandstop response. To this aim, complementary split-ring resonators are chosen as the basic components for common-mode rejection. To illustrate the advantages of using glide symmetry, three implementations are studied and compared. The results reveal that glide symmetry offers the best performance in terms of common-mode rejection level and fractional bandwidth. Furthermore, glide symmetry barely affects the integrity of the differential mode. A prototype of each of the considered symmetries has been designed, simulated, and tested for practical validation. Good agreement is observed between the simulated and measured results, experimentally demonstrating the advantages of glide symmetry.
|
|
| 24. |
|
|
| 25. |
- Ferrando, Carlos, et al.
(författare)
-
Effects of oxygen on post-surgical infections during an individualised perioperative open-lung ventilatory strategy : a randomised controlled trial
- 2020
-
Ingår i: British Journal of Anaesthesia. - : ELSEVIER SCI LTD. - 0007-0912 .- 1471-6771. ; 124:1, s. 110-120
-
Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to examine whether using a high fraction of inspired oxygen (FIO2) in the context of an individualised intra- and postoperative open-lung ventilation approach could decrease surgical site infection (SSI) in patients scheduled for abdominal surgery. Methods: We performed a multicentre, randomised controlled clinical trial in a network of 21 university hospitals from June 6, 2017 to July 19, 2018. Patients undergoing abdominal surgery were randomly assigned to receive a high (0.80) or conventional (0.3) FIO2 during the intraoperative period and during the first 3 postoperative hours. All patients were mechanically ventilated with an open-lung strategy, which included recruitment manoeuvres and individualised positive end-expiratory pressure for the best respiratory-system compliance, and individualised continuous postoperative airway pressure for adequate peripheral oxyhaemoglobin saturation. The primary outcome was the prevalence of SSI within the first 7 postoperative days. The secondary outcomes were composites of systemic complications, length of intensive care and hospital stay, and 6-month mortality. Results: We enrolled 740 subjects: 371 in the high FIO2 group and 369 in the low FIO2 group. Data from 717 subjects were available for final analysis. The rate of SSI during the first postoperative week did not differ between high (8.9%) and low (9.4%) FIO2 groups (relative risk [RR]: 0.94; 95% confidence interval [CI]: 0.59-1.50; P=0.90]). Secondary outcomes, such as atelectasis (7.7% vs 9.8%; RR: 0.77; 95% CI: 0.48-1.25; P=0.38) and myocardial ischaemia (0.6% [n=2] vs 0% [n=0]; P=0.47) did not differ between groups. Conclusions: An oxygenation strategy using high FIO2 compared with conventional FIO2 did not reduce postoperative SSIs in abdominal surgery. No differences in secondary outcomes or adverse events were found.
|
|
| 26. |
- Fonseca, Nelson J. G., et al.
(författare)
-
Fully-Metallic Additively Manufactured Monolithic Double-Ridged Waveguide Rotman Lens in the K/K-a-Band
- 2023
-
Ingår i: Sensors. - : MDPI AG. - 1424-8220. ; 23:14, s. 6573-
-
Tidskriftsartikel (refereegranskat)abstract
- This paper reports on the design and experimental validation of a fully-metallic doubleridged waveguide 10 x 10 Rotman lens additively manufactured as a single part. The wide band operation of this quasi-optical beamformer enables us to cover the uplink and downlink frequencies allocated to satellite communications in the K/K-a-band, from 17.3GHz to 30 GHz. The feeding port design was adjusted to enable vertical printing, thus minimizing the use of supporting structures. A prototype was manufactured and tested. The reported results indicate losses in the range of 0.5 dB in the lower-frequency band and 0.8 dB in the upper-frequency band, including the waveguide transitions added for test purposes. The measured reflection and coupling coefficients remain below 11.5 dB over the operating band. The standard deviation of the residual phase error across the array ports is below 5 degrees in simulation and below 10 degrees in measurements. Array factors synthesized using the scattering parameters confirm the good stability of the beamforming functionality over the wide frequency band analyzed. This monolithic design is a promising step toward more integrated antenna systems, such as a compact dual-stack configuration for planar array design.
|
|
| 27. |
- Franch, Xavier, et al.
(författare)
-
How do Practitioners Perceive the Relevance of Requirements Engineering Research? An Ongoing Study
- 2017
-
Ingår i: 2017 IEEE 25TH INTERNATIONAL REQUIREMENTS ENGINEERING CONFERENCE (RE). - : IEEE. - 2332-6441. - 9781538631911 ; , s. 382-387
-
Konferensbidrag (refereegranskat)abstract
- The relevance of Requirements Engineering (RE) research to practitioners is a prerequisite for problem-driven research in the area and key for a long-term dissemination of research results to everyday practice. To understand better how industry practitioners perceive the practical relevance of RE research, we have initiated the RE-Pract project, an international collaboration conducting an empirical study. This project opts for a replication of previous work done in two different domains and relies on survey research. To this end, we have designed a survey to be sent to several hundred industry practitioners at various companies around the world and ask them to rate their perceived practical relevance of the research described in a sample of 418 RE papers published between 2010 and 2015 at the RE, ICSE, FSE, ESEC/FSE, ESEM and REFSQ conferences. In this paper, we summarize our research protocol and present the current status of our study and the planned future steps.
|
|
| 28. |
|
|
| 29. |
- Hedman, Linnea, et al.
(författare)
-
Receiving support to quit smoking and quit attempts among smokers with and without smoking related diseases : Findings from the EUREST-PLUS ITC Europe Surveys
- 2018
-
Ingår i: Tobacco Induced Diseases. - Heraklion : European Publishing. - 1617-9625. ; 16
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION Having a chronic disease either caused or worsened by tobacco smoking does not always translate into quitting smoking. Although smoking cessation is one of the most cost-effective medical interventions, it remains poorly implemented in healthcare settings. The aim was to examine whether smokers with chronic and respiratory diseases were more likely to receive support to quit smoking by a healthcare provider or make a quit attempt than smokers without these diseases.METHODS This population-based study included a sample of 6011 adult smokers in six European countries. The participants were interviewed face-to-face and asked questions on sociodemographic characteristics, current diagnoses for chronic diseases, healthcare visits in the last 12 months and, if so, whether they had received any support to quit smoking. Questions on smoking behavior included nicotine dependence, motivation to quit smoking and quit attempts in the last 12 months. The results are presented as weighted percentages with 95% confidence intervals (CI) and as adjusted odds ratios with 95% CI based on logistic regression analyses.RESULTS Smokers with chronic respiratory disease, those aged 55 years and older, as well as those with one or more chronic diseases were more likely to receive smoking cessation advice from a healthcare professional. Making a quit attempt in the last year was related to younger age, high educational level, higher motivation to quit, lower nicotine dependence and having received advice to quit from a healthcare professional but not with having chronic diseases. There were significant differences between countries with smokers in Romania consistently reporting more support to quit as well as quit attempts.CONCLUSIONS Although smokers with respiratory disease did indeed receive smoking cessation support more often than smokers without disease, many smokers did not receive any advice or support to quit during a healthcare visit.
|
|
| 30. |
- Hibar, Derrek P., et al.
(författare)
-
Novel genetic loci associated with hippocampal volume
- 2017
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
|
|
| 31. |
- Jimenez-del-Toro, Oscar, et al.
(författare)
-
Cloud-Based Evaluation of Anatomical Structure Segmentation and Landmark Detection Algorithms : VISCERAL Anatomy Benchmarks
- 2016
-
Ingår i: IEEE Transactions on Medical Imaging. - : Institute of Electrical and Electronics Engineers (IEEE). - 0278-0062 .- 1558-254X. ; 35:11, s. 2459-2475
-
Tidskriftsartikel (refereegranskat)abstract
- Variations in the shape and appearance of anatomical structures in medical images are often relevant radiological signs of disease. Automatic tools can help automate parts of this manual process. A cloud-based evaluation framework is presented in this paper including results of benchmarking current state-of-the-art medical imaging algorithms for anatomical structure segmentation and landmark detection: the VISCERAL Anatomy benchmarks. The algorithms are implemented in virtual machines in the cloud where participants can only access the training data and can be run privately by the benchmark administrators to objectively compare their performance in an unseen common test set. Overall, 120 computed tomography and magnetic resonance patient volumes were manually annotated to create a standard Gold Corpus containing a total of 1295 structures and 1760 landmarks. Ten participants contributed with automatic algorithms for the organ segmentation task, and three for the landmark localization task. Different algorithms obtained the best scores in the four available imaging modalities and for subsets of anatomical structures. The annotation framework, resulting data set, evaluation setup, results and performance analysis from the three VISCERAL Anatomy benchmarks are presented in this article. Both the VISCERAL data set and Silver Corpus generated with the fusion of the participant algorithms on a larger set of non-manually-annotated medical images are available to the research community.
|
|
| 32. |
- Jones, Benedict C, et al.
(författare)
-
To which world regions does the valence-dominance model of social perception apply?
- 2021
-
Ingår i: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 5:1, s. 159-169
-
Tidskriftsartikel (refereegranskat)abstract
- Over the past 10 years, Oosterhof and Todorov's valence-dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov's methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov's original analysis strategy, the valence-dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence-dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1 .
|
|
| 33. |
- Kobialka, Piotr, et al.
(författare)
-
The onset of PI3K-related vascular malformations occurs during angiogenesis and is prevented by the AKT inhibitor miransertib
- 2022
-
Ingår i: EMBO Molecular Medicine. - : EMBO Press. - 1757-4676 .- 1757-4684. ; 14:7
-
Tidskriftsartikel (refereegranskat)abstract
- Low-flow vascular malformations are congenital overgrowths composed of abnormal blood vessels potentially causing pain, bleeding and obstruction of different organs. These diseases are caused by oncogenic mutations in the endothelium, which result in overactivation of the PI3K/AKT pathway. Lack of robust in vivo preclinical data has prevented the development and translation into clinical trials of specific molecular therapies for these diseases. Here, we demonstrate that the Pik3caH1047R activating mutation in endothelial cells triggers a transcriptome rewiring that leads to enhanced cell proliferation. We describe a new reproducible preclinical in vivo model of PI3K-driven vascular malformations using the postnatal mouse retina. We show that active angiogenesis is required for the pathogenesis of vascular malformations caused by activating Pik3ca mutations. Using this model, we demonstrate that the AKT inhibitor miransertib both prevents and induces the regression of PI3K-driven vascular malformations. We confirmed the efficacy of miransertib in isolated human endothelial cells with genotypes spanning most of human low-flow vascular malformations.
|
|
| 34. |
- Kristjansdottir, Gudlaug, et al.
(författare)
-
Interferon Regulatory Factor 5 (IRF5) Gene Variants are Associated with Multiple Sclerosis in Three Distinct Populations
- 2008
-
Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 45:6, s. 362-369
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: IRF5 is a transcription factor involved both in the type I interferon and the toll-like receptor signalling pathways. Previously, IRF5 has been found to be associated with systemic lupus erythematosus, rheumatoid arthritis and inflammatory bowel diseases. Here we investigated whether polymorphisms in the IRF5 gene would be associated with yet another disease with features of autoimmunity, multiple sclerosis (MS). METHODS: We genotyped nine single nucleotide polymorphisms and one insertion-deletion polymorphism in the IRF5 gene in a collection of 2337 patients with MS and 2813 controls from three populations: two case-control cohorts from Spain and Sweden, and a set of MS trio families from Finland. RESULTS: Two single nucleotide polymorphism (SNPs) (rs4728142, rs3807306), and a 5 bp insertion-deletion polymorphism located in the promoter and first intron of the IRF5 gene, showed association signals with values of p<0.001 when the data from all cohorts were combined. The predisposing alleles were present on the same common haplotype in all populations. Using electrophoretic mobility shift assays we observed allele specific differences in protein binding for the SNP rs4728142 and the 5 bp indel, and by a proximity ligation assay we demonstrated increased binding of the transcription factor SP1 to the risk allele of the 5 bp indel. CONCLUSION: These findings add IRF5 to the short list of genes shown to be associated with MS in more than one population. Our study adds to the evidence that there might be genes or pathways that are common in multiple autoimmune diseases, and that the type I interferon system is likely to be involved in the development of these diseases.
|
|
| 35. |
- Lee, Byung-Boong, et al.
(författare)
-
Venous hemodynamic changes in lower limb venous disease : the UIP consensus according to scientific evidence
- 2016
-
Ingår i: International Journal of Angiology. - : Springer. - 0392-9590 .- 1827-1839. ; 35:3, s. 236-352
-
Tidskriftsartikel (refereegranskat)abstract
- There are excellent guidelines for clinicians to manage venous diseases but few reviews to assess their hemodynamic background. Hemodynamic concepts that evolved in the past have largely remained unchallenged in recent decades, perhaps due to their often complicated nature and in part due to emergence of new diagnostic techniques. Duplex ultrasound scanning and other imaging techniques which evolved in the latter part of the 20th century have dominated investigation. They have greatly improved our understanding of the anatomical patterns of venous reflux and obstruction. However, they do not provide the physiological basis for understanding the hemodynamics of flow, pressure, compliance and resistance. Hemodynamic investigations appear to provide a better correlation with post-treatment clinical outcome and quality of life than ultrasound findings. There is a far better prospect for understanding the complete picture of the patient's disability and response to management by combining ultrasound with hemodynamic studies. Accordingly, at the instigation of Dr Angelo Scuderi, the Union Internationale de Phlebologie (UIP) executive board commissioned a large number of experts to assess all aspects of management for venous disease by evidence-based principles. These included experts from various member societies including the European Venous Forum (EVF), American Venous Forum (AVF), American College of Phlebology (ACP) and Cardiovascular Disease Educational and Research Trust (CDERT). Their aim was to confirm or dispel long-held hemodynamic principles and to provide a comprehensive review of venous hemodynamic concepts underlying the pathophysiology of lower limb venous disorders, their usefulness for investigating patients and the relevant hemodynamic changes associated with various forms of treatment. Chapter 1 is devoted to basic hemodynamic concepts and normal venous physiology. Chapter 2 presents the mechanism and magnitude of hemodynamic changes in acute deep vein thrombosis indicating their pathophysiological and clinical significance. Chapter 3 describes the hemodynamic changes that occur in different classes of chronic venous disease and their relation to the anatomic extent of disease in the macrocirculation and microcirculation. The next four chapters (Chapters 4-7) describe the hemodynamic changes resulting from treatment by compression using different materials, intermittent compression devices, pharmacological agents and finally surgical or endovenous ablation. Chapter 8 discusses the unique hemodynamic features associated with alternative treatment techniques used by the CHIVA and ASVAL. Chapter 9 describes the hemodynamic effects following treatment to relieve pelvic reflux and obstruction. Finally, Chapter 10 demonstrates that contrary to general belief there is a moderate to good correlation between certain hemodynamic measurements and clinical severity of chronic venous disease. The authors believe that this document will be a timely asset to both clinicians and researchers alike. It is directed towards surgeons and physicians who are anxious to incorporate the conclusions of research into their daily practice. It is also directed to postgraduate trainees, vascular technologists and bioengineers, particularly to help them understand the hemodynamic background to pathophysiology, investigations and treatment of patients with venous disorders. Hopefully it will be a platform for those who would like to embark on new research in the field of venous disease.
|
|
| 36. |
- Li, Xuexin, et al.
(författare)
-
The anti-leprosy drug clofazimine reduces polyQ toxicity through activation of PPARγ
- 2024
-
Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 103
-
Tidskriftsartikel (refereegranskat)abstract
- Background: PolyQ diseases are autosomal dominant neurodegenerative disorders caused by the expansion of CAG repeats. While of slow progression, these diseases are ultimately fatal and lack effective therapies.Methods: A high-throughput chemical screen was conducted to identify drugs that lower the toxicity of a protein containing the fi rst exon of Huntington's disease (HD) protein huntingtin (HTT) harbouring 94 glutamines (Htt-Q94). 94 ). Candidate drugs were tested in a wide range of in vitro and in vivo models of polyQ toxicity.Findings: The chemical screen identified fi ed the anti-leprosy drug clofazimine as a hit, which was subsequently validated in several in vitro models. Computational analyses of transcriptional signatures revealed that the effect of clofazimine was due to the stimulation of mitochondrial biogenesis by peroxisome proliferator-activated receptor gamma (PPARγ). In agreement with this, clofazimine rescued mitochondrial dysfunction triggered by Htt-Q94 expression. Importantly, clofazimine also limited polyQ toxicity in developing zebrafish fish and neuron-specific worm models of polyQ disease.Interpretation: Our results support the potential of repurposing the antimicrobial drug clofazimine for the treatment of polyQ diseases.
|
|
| 37. |
- Llewellyn, Tim, et al.
(författare)
-
BONSEYES : Platform for Open Development of Systems of Artificial Intelligence
- 2017
-
Konferensbidrag (refereegranskat)abstract
- The Bonseyes EU H2020 collaborative project aims to develop a platform consisting of a Data Marketplace, a Deep Learning Toolbox, and Developer Reference Platforms for organizations wanting to adopt Artificial Intelligence. The project will be focused on using artificial intelligence in low power Internet of Things (IoT) devices ("edge computing"), embedded computing systems, and data center servers ("cloud computing"). It will bring about orders of magnitude improvements in efficiency, performance, reliability, security, and productivity in the design and programming of systems of artificial intelligence that incorporate Smart Cyber-Physical Systems (CPS). In addition, it will solve a causality problem for organizations who lack access to Data and Models. Its open software architecture will facilitate adoption of the whole concept on a wider scale. To evaluate the effectiveness, technical feasibility, and to quantify the real-world improvements in efficiency, security, performance, effort and cost of adding AI to products and services using the Bonseyes platform, four complementary demonstrators will be built. Bonseyes platform capabilities are aimed at being aligned with the European FI-PPP activities and take advantage of its flagship project FIWARE. This paper provides a description of the project motivation, goals and preliminary work.
|
|
| 38. |
- Lopez-Contreras, Andres J., et al.
(författare)
-
Increased Rrm2 gene dosage reduces fragile site breakage and prolongs survival of ATR mutant mice
- 2015
-
Ingår i: Genes & Development. - : Cold Spring Harbor Laboratory Press. - 0890-9369 .- 1549-5477. ; 29:7, s. 690-695
-
Tidskriftsartikel (refereegranskat)abstract
- In Saccharomyces cerevisiae, absence of the checkpoint kinase Mec1 (ATR) is viable upon mutations that increase the activity of the ribonucleotide reductase (RNR) complex. Whether this pathway is conserved in mammals remains unknown. Here we show that cells from mice carrying extra alleles of the RNR regulatory subunit RRM2 (Rrm2(TG)) present supraphysiological RNR activity and reduced chromosomal breakage at fragile sites. Moreover, increased Rrm2 gene dosage significantly extends the life span of ATR mutant mice. Our study reveals the first genetic condition in mammals that reduces fragile site expression and alleviates the severity of a progeroid disease by increasing RNR activity. Supplemental material is available for this article.
|
|
| 39. |
- Mahajan, Anubha, et al.
(författare)
-
Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
- 2018
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:4, s. 559-571
-
Tidskriftsartikel (refereegranskat)abstract
- We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10−7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.
|
|
| 40. |
- Marto, João Pedro, et al.
(författare)
-
Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry.
- 2023
-
Ingår i: Neurology. - 1526-632X. ; 100:7
-
Tidskriftsartikel (refereegranskat)abstract
- COVID-19-related inflammation, endothelial dysfunction, and coagulopathy may increase the bleeding risk and lower the efficacy of revascularization treatments in patients with acute ischemic stroke (AIS). We aimed to evaluate the safety and outcomes of revascularization treatments in patients with AIS and COVID-19.This was a retrospective multicenter cohort study of consecutive patients with AIS receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021 tested for severe acute respiratory syndrome coronavirus 2 infection. With a doubly robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT).Of a total of 15,128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19; of those, 5,848 (38.7%) patients received IVT-only and 9,280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted OR 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour mortality (OR 2.47; 95% CI 1.58-3.86), and 3-month mortality (OR 1.88; 95% CI 1.52-2.33). Patients with COVID-19 also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60).Patients with AIS and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 patients receiving treatment. Current available data do not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in patients with COVID-19 or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring, and establishing prognosis.The study was registered under ClinicalTrials.gov identifier NCT04895462.
|
|
| 41. |
- Maxwell, Tania L., et al.
(författare)
-
Global dataset of soil organic carbon in tidal marshes
- 2023
-
Ingår i: Scientific Data. - : Springer Nature. - 2052-4463. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- Tidal marshes store large amounts of organic carbon in their soils. Field data quantifying soil organic carbon (SOC) stocks provide an important resource for researchers, natural resource managers, and policy-makers working towards the protection, restoration, and valuation of these ecosystems. We collated a global dataset of tidal marsh soil organic carbon (MarSOC) from 99 studies that includes location, soil depth, site name, dry bulk density, SOC, and/or soil organic matter (SOM). The MarSOC dataset includes 17,454 data points from 2,329 unique locations, and 29 countries. We generated a general transfer function for the conversion of SOM to SOC. Using this data we estimated a median (± median absolute deviation) value of 79.2 ± 38.1 Mg SOC ha−1 in the top 30 cm and 231 ± 134 Mg SOC ha−1 in the top 1 m of tidal marsh soils globally. This data can serve as a basis for future work, and may contribute to incorporation of tidal marsh ecosystems into climate change mitigation and adaptation strategies and policies.
|
|
| 42. |
- Monelli, Erika, et al.
(författare)
-
Angiocrine polyamine production regulates adiposity
- 2022
-
Ingår i: Nature Metabolism. - : Springer Nature. - 2522-5812. ; 4:3, s. 327-
-
Tidskriftsartikel (refereegranskat)abstract
- Reciprocal interactions between endothelial cells (ECs) and adipocytes are fundamental to maintain white adipose tissue (WAT) homeostasis, as illustrated by the activation of angiogenesis upon WAT expansion, a process that is impaired in obesity. However, the molecular mechanisms underlying the crosstalk between ECs and adipocytes remain poorly understood. Here, we show that local production of polyamines in ECs stimulates adipocyte lipolysis and regulates WAT homeostasis in mice. We promote enhanced cell-autonomous angiogenesis by deleting Pten in the murine endothelium. Endothelial Pten loss leads to a WAT-selective phenotype, characterized by reduced body weight and adiposity in pathophysiological conditions. This phenotype stems from enhanced fatty acid beta-oxidation in ECs concomitant with a paracrine lipolytic action on adipocytes, accounting for reduced adiposity. Combined analysis of murine models, isolated ECs and human specimens reveals that WAT lipolysis is mediated by mTORC1-dependent production of polyamines by ECs. Our results indicate that angiocrine metabolic signals are important for WAT homeostasis and organismal metabolism. Endothelial cells in white adipose tissue are shown to produce polyamines, which regulate adipocyte lipolysis, thus demonstrating how local angiocrine signals contribute to healthy adipose tissue homeostasis.
|
|
| 43. |
- Moshontz, Hannah, et al.
(författare)
-
The Psychological Science Accelerator: Advancing Psychology Through a Distributed Collaborative Network
- 2018
-
Ingår i: Advances in Methods and Practices in Psychological Science. - : SAGE Publications. - 2515-2459 .- 2515-2467. ; 1:4, s. 501-515
-
Tidskriftsartikel (refereegranskat)abstract
- Concerns about the veracity of psychological research have been growing. Many findings in psychological science are based on studies with insufficient statistical power and nonrepresentative samples, or may otherwise be limited to specific, ungeneralizable settings or populations. Crowdsourced research, a type of large-scale collaboration in which one or more research projects are conducted across multiple lab sites, offers a pragmatic solution to these and other current methodological challenges. The Psychological Science Accelerator (PSA) is a distributed network of laboratories designed to enable and support crowdsourced research projects. These projects can focus on novel research questions or replicate prior research in large, diverse samples. The PSA’s mission is to accelerate the accumulation of reliable and generalizable evidence in psychological science. Here, we describe the background, structure, principles, procedures, benefits, and challenges of the PSA. In contrast to other crowdsourced research networks, the PSA is ongoing (as opposed to time limited), efficient (in that structures and principles are reused for different projects), decentralized, diverse (in both subjects and researchers), and inclusive (of proposals, contributions, and other relevant input from anyone inside or outside the network). The PSA and other approaches to crowdsourced psychological science will advance understanding of mental processes and behaviors by enabling rigorous research and systematic examination of its generalizability.
|
|
| 44. |
- Mouris, Boules Atef, et al.
(författare)
-
Glide Symmetry Applied to Printed Common-Mode Rejection Filters
- 2022
-
Ingår i: IEEE transactions on microwave theory and techniques. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9480 .- 1557-9670. ; 70:2, s. 1198-1210
-
Tidskriftsartikel (refereegranskat)abstract
- In this article, we present a novel application of glide symmetry to differential lines with common-mode (CM) rejection filter properties. Two different topologies are investigated. First, glide symmetry is applied to a pair of differential lines where ground-connected mushrooms are employed as a CM rejection structure. The same idea is also used in a pair of differential lines where defective ground structures are introduced to stop the CM propagation. It is demonstrated that the CM rejection bandwidth is drastically increased when glide symmetry is exploited in both topologies when compared with their corresponding structures without glide symmetry. Furthermore, we show that the differential-mode propagation is hardly affected by the use of glide symmetry, ensuring the good integrity of the transmitted information. Experimental demonstration for both mushroom and defected ground structure is provided. Good agreement between simulations and measurements results is observed.
|
|
| 45. |
- Mouris, Boules Atef, et al.
(författare)
-
Glide Symmetry to Improve the Bandgap Operation of Periodic Microstrip Defected Ground Structures
- 2020
-
Ingår i: 2020 50th european microwave conference (EuMC). - : IEEE. ; , s. 483-486
-
Konferensbidrag (refereegranskat)abstract
- A novel one-dimensional periodic planar defected ground structure exploiting glide symmetry is proposed here. The planar structure is designed to operate as an electromagnetic bandgap structure that avoids the use of vias. Simulation results show that the glide-symmetric structure offers a wider rejection bandwidth as well as a higher rejection level than the conventional structure (without glide symmetry). Measurement results of the fabricated prototypes are provided to verify the simulation results.
|
|
| 46. |
- Mouris, Boules Atef, et al.
(författare)
-
On the Increment of the Bandwidth of Mushroom-Type EBG Structures With Glide Symmetry
- 2020
-
Ingår i: IEEE transactions on microwave theory and techniques. - 0018-9480 .- 1557-9670.
-
Tidskriftsartikel (refereegranskat)abstract
- Mushroom-type electromagnetic bandgap (EBG) structures are known to operate as high-impedance surfaces at low-frequency bands. They are broadly used in the microwave regime. However, one of the main drawbacks of mushroom-type EBG structures is their narrow bandwidth. In this article, we propose a mushroom-type EBG structure with glide-symmetric edge vias to increase the operational bandwidth. This bandwidth increment is explained by the physical insight provided by an equivalent circuit model of the structure as well as the description of the field behavior. Simulation and measurement results show an improvement of approximately 67% over the case without glide symmetry in the structure. We conclude that applying glide symmetry to the mushroom-type EBG structures can improve their bandwidth without adding additional manufacturing costs.
|
|
| 47. |
- Nguyen, Thanh N, et al.
(författare)
-
Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.
- 2023
-
Ingår i: Neurology. - 1526-632X. ; 100:4
-
Tidskriftsartikel (refereegranskat)abstract
- Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
|
|
| 48. |
- Padilla, Pablo, et al.
(författare)
-
Broken Glide-Symmetric Holey Structures for Bandgap Selection in Gap-Waveguide Technology
- 2019
-
Ingår i: IEEE Microwave and Wireless Components Letters. - : IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. - 1531-1309 .- 1558-1764. ; 29:5, s. 327-329
-
Tidskriftsartikel (refereegranskat)abstract
- In this letter, we propose a new technique to tune the bandgap in gap-waveguide technology based on broken glide-symmetric holey structures. We demonstrate that breaking the glide-symmetry in a proper manner provokes the presence of a passband within the bandgap due to the frequency sweep of the second propagating mode. This passband generates field leakage in the gap that is translated into a filtering property. This filtering effect may be used to reduce or eliminate filters in large complex devices. In order to avoid undesired coupling due to the leakage from the air gap between the plates, an absorbing sheet is proposed to dissipate the undesired fields. This idea has been numerically studied and experimentally validated with a specific design, a WR15-size gap-waveguide prototype with glide-symmetric holes with filtering properties.
|
|
| 49. |
- Padilla, P., et al.
(författare)
-
Glide-symmetric holey structures with selected bandgaps for gap-waveguide technology
- 2018
-
Ingår i: IET Conference Publications. - : Institution of Engineering and Technology.
-
Konferensbidrag (refereegranskat)abstract
- Here, we propose a new technique to accurately define and select the bandgap regions in gap waveguide technology based on glide-symmetric holey structures. This selection is accomplished by breaking the symmetry of the periodic structure. The advantage of this proposal is that filtering properties are added intrinsically in the waveguides, reducing the total complexity of the overall device, in which additional filters may not be necessary.
|
|
| 50. |
- Patil, Ajinkya H., et al.
(författare)
-
Constraining the epoch of reionization with the variance statistic : simulations of the LOFAR case
- 2014
-
Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 443:2, s. 1113-1124
-
Tidskriftsartikel (refereegranskat)abstract
- Several experiments are underway to detect the cosmic-redshifted 21-cm signal from neutral hydrogen from the Epoch of Reionization (EoR). Due to their very low signal-to-noise ratio, these observations aim for a statistical detection of the signal by measuring its power spectrum. We investigate the extraction of the variance of the signal as a first step towards detecting and constraining the global history of the EoR. Signal variance is the integral of the signal's power spectrum, and it is expected to be measured with a high significance. We demonstrate this through results from a simulation and parameter estimation pipeline developed for the Low-Frequency Array (LOFAR)-EoR experiment. We show that LOFAR should be able to detect the EoR in 600 h of integration using the variance statistic. Additionally, the redshift (z(r)) and duration (Delta z) of reionization can be constrained assuming a parametrization. We use an EoR simulation of z(r) = 7.68 and Delta(z) = 0.43 to test the pipeline. We are able to detect the simulated signal with a significance of four standard deviations and extract the EoR parameters as z(r) = 7.72(-0.18)(+0.37) and Delta z = 0.53(-0.23)(+0.12) in 600 h, assuming that systematic errors can be adequately controlled. We further show that the significance of detection and constraints on EoR parameters can be improved by measuring the cross-variance of the signal by cross-correlating consecutive redshift bins.
|
|
