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| 11. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 12. |
- Ferreira, Mjv, et al.
(författare)
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Poster Session 3 : Tuesday 5 May 2015, 08
- 2015
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Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
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Tidskriftsartikel (refereegranskat)
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| 13. |
- Joshi, Peter K, et al.
(författare)
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Directional dominance on stature and cognition in diverse human populations
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
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Tidskriftsartikel (refereegranskat)abstract
- Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
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| 14. |
- Teslovich, Tanya M., et al.
(författare)
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Biological, clinical and population relevance of 95 loci for blood lipids
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7307, s. 707-713
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Tidskriftsartikel (refereegranskat)abstract
- Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P<5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.
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| 15. |
- Palmer, Nicholette D, et al.
(författare)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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| 16. |
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| 17. |
- Wuttke, Matthias, et al.
(författare)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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| 18. |
- Pattaro, Cristian, et al.
(författare)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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| 19. |
- Tinetti, G., et al.
(författare)
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A chemical survey of exoplanets with ARIEL
- 2018
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Ingår i: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 46:1, s. 135-209
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Tidskriftsartikel (refereegranskat)abstract
- Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.
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| 20. |
- Botvinik-Nezer, Rotem, et al.
(författare)
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Variability in the analysis of a single neuroimaging dataset by many teams
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 582, s. 84-88
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Tidskriftsartikel (refereegranskat)abstract
- Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed. The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
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| 21. |
- Chasman, Daniel I., et al.
(författare)
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Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:24, s. 5329-5343
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Tidskriftsartikel (refereegranskat)abstract
- In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P 5.6 10(9)) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 10(4)2.2 10(7). Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general.
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| 22. |
- Guglielmo, V., et al.
(författare)
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The XXL Survey: XXII. the XXL-North spectrophotometric sample and galaxy stellar mass function in X-ray detected groups and clusters
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 620
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Tidskriftsartikel (refereegranskat)abstract
- Context. The fraction of galaxies bound in groups in the nearby Universe is high (50% at z ∼ 0). Systematic studies of galaxy properties in groups are important in order to improve our understanding of the evolution of galaxies and of the physical phenomena occurring within this environment. Aims. We have built a complete spectrophotometric sample of galaxies within X-ray detected, optically spectroscopically confirmed groups and clusters (G&C), covering a wide range of halo masses at z ≤ 0.6. Methods. In the context of the XXL survey, we analyse a sample of 164 G&C in the XXL-North region (XXL-N), at z ≤ 0.6, with a wide range of virial masses (1.24 × 1013 ≤ M500,scal(Mo) ≤ 6.63 × 1014) and X-ray luminosities ((2.27 × 1041 ≤ L500,scalXXL(erg-s-1) ≤ 2.15 × 1044)). The G&C are X-ray selected and spectroscopically confirmed. We describe the membership assignment and the spectroscopic completeness analysis, and compute stellar masses. As a first scientific exploitation of the sample, we study the dependence of the galaxy stellar mass function (GSMF) on global environment. Results. We present a spectrophotometric characterisation of the G&C and their galaxies. The final sample contains 132 G&C, 22 111 field galaxies and 2225 G&C galaxies with r-band magnitude <20. Of the G&C, 95% have at least three spectroscopic members, and 70% at least ten. The shape of the GSMF seems not to depend on environment (field versus G&C) or X-ray luminosity (used as a proxy for the virial mass of the system). These results are confirmed by the study of the correlation between mean stellar mass of G&C members and L500,scalXXL. We release the spectrophotometric catalogue of galaxies with all the quantities computed in this work. Conclusions. As a first homogeneous census of galaxies within X-ray spectroscopically confirmed G&C at these redshifts, this sample will allow environmental studies of the evolution of galaxy properties.
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| 23. |
- Parsa, Afshin, et al.
(författare)
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Common Variants in Mendelian Kidney Disease Genes and Their Association with Renal Function
- 2013
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 24:12, s. 2105-2117
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Tidskriftsartikel (refereegranskat)abstract
- Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.
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| 24. |
- Pattaro, Cristian, et al.
(författare)
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Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function
- 2012
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 8:3, s. e1002584-
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genomewide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.
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| 25. |
- Alves, Dimas, I, et al.
(författare)
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Incoherent Change Detection Methods for Wavelength-Resolution SAR Image Stacks Based on Masking Techniques
- 2020
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Ingår i: 2020 IEEE National Radar Conference - Proceedings. - : IEEE. - 9781728189420
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Konferensbidrag (refereegranskat)abstract
- This paper presents two incoherent change detection methods for wavelength-resolution synthetic aperture radars (SAR) image stacks based on masking techniques. The first technique proposed is the Simple Masking Detection (SMD). This method uses the statistical behavior of pixels-sets in the image stack to create a binary mask, which is used to remove pixels that are not related to changes in a surveillance image from the same interest region. The second technique is the Multiple Concatenated Masking Detection (MCMD), which produces a more selective mask than the SMD by concatenating multiple masks from different image stacks. The MCMD can be used in specific applications where multiple stacks share common patterns of target deployments. Both proposed techniques were evaluated using 24 incoherent SAR images obtained by the CARABAS II system. The experimental results revealed that the proposed detection methods have better performance in terms of probability of detection and false alarm rate when compared with other change detection techniques, especially for high detection probabilities scenarios.
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| 26. |
- Alves, Dimas I., et al.
(författare)
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Neyman-Pearson Criterion-Based Change Detection Methods for Wavelength-Resolution SAR Image Stacks
- 2022
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Ingår i: IEEE Geoscience and Remote Sensing Letters. - : Institute of Electrical and Electronics Engineers Inc.. - 1545-598X .- 1558-0571. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- This letter presents two new change detection (CD) methods for synthetic aperture radar (SAR) image stacks based on the Neyman-Pearson criterion. The first proposed method uses the data from wavelength-resolution images stack to obtain background statistics, which are used in a hypothesis test to detect changes in a surveillance image. The second method considers a priori information about the targets to obtain the target statistics, which are used together with the previously obtained background statistics, to perform a hypothesis test to detect changes in a surveillance image. A straightforward processing scheme is presented to test the proposed CD methods. To assess the performance of both proposed methods, we considered the coherent all radio band sensing (CARABAS)-II SAR images. In particular, to obtain the temporal background statistics required by the derived methods, we used stacks with six images. The experimental results show that the proposed techniques provide a competitive performance in terms of probability of detection and false alarm rate compared with other CD methods. CCBY
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| 27. |
- Atun, Rifat, et al.
(författare)
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Sustainable care for children with cancer : a Lancet Oncology Commission
- 2020
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Ingår i: The Lancet Oncology. - 1470-2045. ; 21:4, s. 185-224
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Forskningsöversikt (refereegranskat)abstract
- We estimate that there will be 13·7 million new cases of childhood cancer globally between 2020 and 2050. At current levels of health system performance (including access and referral), 6·1 million (44·9%) of these children will be undiagnosed. Between 2020 and 2050, 11·1 million children will die from cancer if no additional investments are made to improve access to health-care services or childhood cancer treatment. Of this total, 9·3 million children (84·1%) will be in low-income and lower-middle-income countries. This burden could be vastly reduced with new funding to scale up cost-effective interventions. Simultaneous comprehensive scale-up of interventions could avert 6·2 million deaths in children with cancer in this period, more than half (56·1%) of the total number of deaths otherwise projected. Taking excess mortality risk into consideration, this reduction in the number of deaths is projected to produce a gain of 318 million life-years. In addition, the global lifetime productivity gains of US$2580 billion in 2020–50 would be four times greater than the cumulative treatment costs of $594 billion, producing a net benefit of $1986 billion on the global investment: a net return of $3 for every $1 invested. In sum, the burden of childhood cancer, which has been grossly underestimated in the past, can be effectively diminished to realise massive health and economic benefits and to avert millions of needless deaths.
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| 28. |
- Aulchenko, Yurii S, et al.
(författare)
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Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:1, s. 47-55
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Tidskriftsartikel (refereegranskat)abstract
- Recent genome-wide association (GWA) studies of lipids have been conducted in samples ascertained for other phenotypes, particularly diabetes. Here we report the first GWA analysis of loci affecting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform. Our study included a total of 17,797-22,562 persons, aged 18-104 years and from geographic regions spanning from the Nordic countries to Southern Europe. We established 22 loci associated with serum lipid levels at a genome-wide significance level (P < 5 x 10(-8)), including 16 loci that were identified by previous GWA studies. The six newly identified loci in our cohort samples are ABCG5 (TC, P = 1.5 x 10(-11); LDL, P = 2.6 x 10(-10)), TMEM57 (TC, P = 5.4 x 10(-10)), CTCF-PRMT8 region (HDL, P = 8.3 x 10(-16)), DNAH11 (LDL, P = 6.1 x 10(-9)), FADS3-FADS2 (TC, P = 1.5 x 10(-10); LDL, P = 4.4 x 10(-13)) and MADD-FOLH1 region (HDL, P = 6 x 10(-11)). For three loci, effect sizes differed significantly by sex. Genetic risk scores based on lipid loci explain up to 4.8% of variation in lipids and were also associated with increased intima media thickness (P = 0.001) and coronary heart disease incidence (P = 0.04). The genetic risk score improves the screening of high-risk groups of dyslipidemia over classical risk factors.
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| 29. |
- Babes, Alexandru, et al.
(författare)
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Photosensitization in porphyrias and photodynamic therapy involves TRPA1 and TRPV1
- 2016
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Ingår i: The Journal of Neuroscience. - 0270-6474. ; 36:19, s. 5264-5278
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Tidskriftsartikel (refereegranskat)abstract
- Photosensitization, an exaggerated sensitivity to harmless light, occurs genetically in rare diseases, such as porphyrias, and in photodynamic therapy where short-term toxicity is intended. A common feature is the experience of pain from bright light. In human subjects, skin exposure to 405 nm light induced moderate pain, which was intensified by pretreatment with aminolevulinic acid. In heterologous expression systems and cultured sensory neurons, exposure to blue light activated TRPA1 and, to a lesser extent, TRPV1 channels in the absence of additional photosensitization. Pretreatment with aminolevulinic acid or with protoporphyrin IX dramatically increased the light sensitivity of both TRPA1 and TRPV1 via generation of reactive oxygen species. Artificial lipid bilayers equipped with purified human TRPA1 showed substantial single-channel activity only in the presence of protoporphyrin IX and blue light. Photosensitivity and photosensitization could be demonstrated in freshly isolated mouse tissues and led to TRP channel-dependent release of proinflammatory neuropeptides upon illumination. With antagonists in clinical development, these findings may help to alleviate pain during photodynamic therapy and also allow for disease modification in porphyria patients.
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| 30. |
- Bernatchez, Louis, et al.
(författare)
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Harnessing the Power of Genomics to Secure the Future of Seafood
- 2017
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Ingår i: Trends in Ecology and Evolution. - : Elsevier BV. - 0169-5347. ; 32:9, s. 665-680
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Forskningsöversikt (refereegranskat)abstract
- Best use of scientific knowledge is required to maintain the fundamental role of seafood in human nutrition. While it is acknowledged that genomic-based methods allow the collection of powerful data, their value to inform fisheries management, aquaculture, and biosecurity applications remains underestimated. We review genomic applications of relevance to the sustainable management of seafood resources, illustrate the benefits of, and identify barriers to their integration. We conclude that the value of genomic information towards securing the future of seafood does not need to be further demonstrated. Instead, we need immediate efforts to remove structural roadblocks and focus on ways that support integration of genomic-informed methods into management and production practices. We propose solutions to pave the way forward. Advancements of genetic technologies now allow the collection of genome-wide data in nonmodel species in a cost-effective manner. These genomic-informed technologies allow addressing a comprehensive spectrum of needs and applications relevant to fisheries, aquaculture, and biosecurity. Genomics tools also improve our understanding of how aquatic organisms adapt and respond to the environment, and improve our ability to monitor environmental variation and exploited species. Genomic approaches are now rapidly replacing traditional genetic markers, but their application in fisheries and aquaculture management has stagnated when compared to agriculture where they have long been used for improved production. There is no reason to further delay the application of genomic tools in fisheries management and aquaculture production.
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| 31. |
- Boeger, Carsten A., et al.
(författare)
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CUBN Is a Gene Locus for Albuminuria
- 2011
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 22:3, s. 555-570
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Tidskriftsartikel (refereegranskat)abstract
- Identification of genetic risk factors for albuminuria may alter strategies for early prevention of CKD progression, particularly among patients with diabetes. Little is known about the influence of common genetic variants on albuminuria in both general and diabetic populations. We performed a meta-analysis of data from 63,153 individuals of European ancestry with genotype information from genome-wide association studies (CKDGen Consortium) and from a large candidate gene study (CARe Consortium) to identify susceptibility loci for the quantitative trait urinary albumin-to-creatinine ratio (UACR) and the clinical diagnosis microalbuminuria. We identified an association between a missense variant (I2984V) in the CUBN gene, which encodes cubilin, and both UACR (P = 1.1 x 10(-11)) and microalbuminuria (P = 0.001). We observed similar associations among 6981 African Americans in the CARe Consortium. The associations between this variant and both UACR and microalbuminuria were significant in individuals of European ancestry regardless of diabetes status. Finally, this variant associated with a 41% increased risk for the development of persistent microalbuminuria during 20 years of follow-up among 1304 participants with type 1 diabetes in the prospective DCCT/EDIC Study. In summary, we identified a missense CUBN variant that associates with levels of albuminuria in both the general population and in individuals with diabetes.
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| 32. |
- Esparza, Alicia, et al.
(författare)
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Asymptotic statistical analysis for model-based control design strategies
- 2011
-
Ingår i: Automatica. - : Elsevier BV. - 0005-1098 .- 1873-2836. ; 47:5, s. 1041-1046
-
Tidskriftsartikel (refereegranskat)abstract
- In this paper, we generalize existing fundamental limitations on the accuracy of the estimation of dynamic models. In addition, we study the large sample statistical behavior of different estimation-based controller design strategies. In particular, fundamental limitations on the closed-loop performance using a controller obtained by Virtual Reference Feedback Tuning (VRFT) are studied. We also extend our results to more general estimation-based control design strategies. We present numerical examples to show the application of our results.
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| 33. |
- Galdino, Lidia, et al.
(författare)
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On the limits of digital back-propagation in the presence of transceiver noise
- 2017
-
Ingår i: Optics Express. - 1094-4087 .- 1094-4087. ; 25:4, s. 4564-4578
-
Tidskriftsartikel (refereegranskat)abstract
- © 2017, OSA - The Optical Society. All rights reserved. This paper investigates the impact of transceiver noise on the performance of digital back-propagation (DBP). A generalized expression to estimate the signal-to-noise ratio (SNR) obtained using DBP in the presence of transceiver noise is described. This new expression correctly accounts for the nonlinear beating between the transceiver noise and the signal in the optical fiber transmission link. The transceiver noise-signal nonlinear beating has been identified as the main reason for the discrepancy between predicted and practical performance of DBP; which has not been previously suggested. This nonlinear beating has been included in the GN model, allowing DBP gains in practical systems to be predicted analytically. Experiments and split-step simulations with and without polarization-mode dispersion (PMD) in the transmission link have been performed. The results show that the impact of transceiver noise greatly outweighs that of PMD, and the analytical expressions are confirmed by the numerical simulations.
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| 34. |
- Godoy, B. I., et al.
(författare)
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A novel input design approach for systems with quantized output data
- 2014
-
Ingår i: 2014 European Control Conference, ECC. - : IEEE. - 9783952426913 ; , s. 1049-1054
-
Konferensbidrag (refereegranskat)abstract
- In this paper, we explore the problem of input design for systems with quantized measurements. For the input design problem, we calculate and optimize a function of the Fisher Information Matrix (FIM). The calculation of the FIM is greatly simplified by using known relationships of the derivative of the likelihood function, and the auxiliary function arising from the Expectation Maximization (EM) algorithm. To optimize the FIM, we design an experiment using a recently published method based on graph theory. A numerical example shows that the proposed experiment can be successfully used in quantized systems.
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| 35. |
- Goodwin, Graham C., et al.
(författare)
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Robust Identification of Process Models from Plant Data
- 2008
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Ingår i: Journal of Process Control. - : Elsevier. - 0959-1524. ; 18:9, s. 810-820
-
Tidskriftsartikel (refereegranskat)abstract
- A precursor to any advanced control solution is the step of obtaining an accurate model of the process. Suitable models can be obtained from phenomenological reasoning, analysis of plant data or a combination of both. Here, we will focus on the problem of estimating (or calibrating) models from plant data. A key goal is to achieve robust identification. By robust we mean that small errors in the hypotheses should lead to small errors in the estimated models. We argue that, in some circumstances, it is essential that special precautions, including discarding some part of the data, be taken to ensure that robustness is preserved. We present several practical case studies to illustrate the results.
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| 36. |
- Gorski, Mathias, et al.
(författare)
-
1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function.
- 2017
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- HapMap imputed genome-wide association studies (GWAS) have revealed >50 loci at which common variants with minor allele frequency >5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value < 5 × 10(-8) previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR < 0.05) genes and 127 significantly (FDR < 0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until whole-genome sequencing becomes feasible in large samples.
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| 37. |
- Gorski, Mathias, et al.
(författare)
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Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies
- 2022
-
Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 102:3, s. 624-639
-
Tidskriftsartikel (refereegranskat)abstract
- Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genomewide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR- baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant- by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with agedependency of genetic cross- section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in- silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03- 1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.
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| 38. |
- Gorski, Mathias, et al.
(författare)
-
Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline
- 2021
-
Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 99:4, s. 926-939
-
Tidskriftsartikel (refereegranskat)abstract
- Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
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| 39. |
- Guglielmo, V., et al.
(författare)
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The XXL Survey: XXX. Characterisation of the XLSSsC N01 supercluster and analysis of the galaxy stellar populations
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 620
-
Tidskriftsartikel (refereegranskat)abstract
- Context. Superclusters form from the largest enhancements in the primordial density perturbation field and extend for tens of Mpc, tracing the large-scale structure of the Universe. X-ray detections and systematic characterisations of superclusters and the properties of their galaxies have only been possible in the last few years. Aims. We characterise XLSSsC N01, a rich supercluster at z ∼ 0.3 detected in the XXL Survey, composed of X-ray clusters of different virial masses and X-ray luminosities. As one of the first studies on this topic, we investigate the stellar populations of galaxies in different environments in the supercluster region. Methods. We study a magnitude-limited (r ≤ 20) and a mass-limited sample (log(M ∗ Mo) ≥ 10.8) of galaxies in the virialised region and in the outskirts of 11 XLSSsC N01 clusters, in high-density field regions, and in the low-density field. We compute the stellar population properties of galaxies using spectral energy distribution (SED) and spectral fitting techniques, and study the dependence of star formation rates (SFR), colours, and stellar ages on environment. Results. For r ≤ 20, the fraction of star-forming/blue galaxies, computed either from the specific-SFR (sSFR) or rest-frame colour, shows depletion within the cluster virial radii, where the number of galaxies with log (sSFR/ yr-1) > -12 and with (g - r) restframe < 0.6 is lower than in the field. For log(M ∗ Mo) ≥ 10.8, no trends with environment emerge, as massive galaxies are mostly already passive in all environments. No differences among low- and high-density field members and cluster members emerge in the sSFR-mass relation in the mass-complete regime. Finally, the luminosity-weighted age-mass relation of the passive populations within cluster virial radii show signatures of recent environmental quenching. Conclusions. The study of luminous and massive galaxies in this supercluster shows that while environment has a prominent role in determining the fractions of star-forming/blue galaxies, its effects on the star formation activity in star-forming galaxies are negligible.
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| 40. |
- Heard-Costa, Nancy L, et al.
(författare)
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NRXN3 is a novel locus for waist circumference : a genome-wide association study from the CHARGE Consortium
- 2009
-
Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 5:6, s. e1000539-
-
Tidskriftsartikel (refereegranskat)abstract
- Central abdominal fat is a strong risk factor for diabetes and cardiovascular disease. To identify common variants influencing central abdominal fat, we conducted a two-stage genome-wide association analysis for waist circumference (WC). In total, three loci reached genome-wide significance. In stage 1, 31,373 individuals of Caucasian descent from eight cohort studies confirmed the role of FTO and MC4R and identified one novel locus associated with WC in the neurexin 3 gene [NRXN3 (rs10146997, p = 6.4×10−7)]. The association with NRXN3 was confirmed in stage 2 by combining stage 1 results with those from 38,641 participants in the GIANT consortium (p = 0.009 in GIANT only, p = 5.3×10−8 for combined analysis, n = 70,014). Mean WC increase per copy of the G allele was 0.0498 z-score units (0.65 cm). This SNP was also associated with body mass index (BMI) [p = 7.4×10−6, 0.024 z-score units (0.10 kg/m2) per copy of the G allele] and the risk of obesity (odds ratio 1.13, 95% CI 1.07–1.19; p = 3.2×10−5 per copy of the G allele). The NRXN3 gene has been previously implicated in addiction and reward behavior, lending further evidence that common forms of obesity may be a central nervous system-mediated disorder. Our findings establish that common variants in NRXN3 are associated with WC, BMI, and obesity.
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| 41. |
- Hicks, Andrew A., et al.
(författare)
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Genetic determinants of circulating sphingolipid concentrations in European populations
- 2009
-
Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 5:10, s. e1000672-
-
Tidskriftsartikel (refereegranskat)abstract
- Sphingolipids have essential roles as structural components of cell membranes and in cell signalling, and disruption of their metabolism causes several diseases, with diverse neurological, psychiatric, and metabolic consequences. Increasingly, variants within a few of the genes that encode enzymes involved in sphingolipid metabolism are being associated with complex disease phenotypes. Direct experimental evidence supports a role of specific sphingolipid species in several common complex chronic disease processes including atherosclerotic plaque formation, myocardial infarction (MI), cardiomyopathy, pancreatic β-cell failure, insulin resistance, and type 2 diabetes mellitus. Therefore, sphingolipids represent novel and important intermediate phenotypes for genetic analysis, yet little is known about the major genetic variants that influence their circulating levels in the general population. We performed a genome-wide association study (GWAS) between 318,237 single-nucleotide polymorphisms (SNPs) and levels of circulating sphingomyelin (SM), dihydrosphingomyelin (Dih-SM), ceramide (Cer), and glucosylceramide (GluCer) single lipid species (33 traits); and 43 matched metabolite ratios measured in 4,400 subjects from five diverse European populations. Associated variants (32) in five genomic regions were identified with genome-wide significant corrected p-values ranging down to 9.08×10−66. The strongest associations were observed in or near 7 genes functionally involved in ceramide biosynthesis and trafficking: SPTLC3, LASS4, SGPP1, ATP10D, and FADS1–3. Variants in 3 loci (ATP10D, FADS3, and SPTLC3) associate with MI in a series of three German MI studies. An additional 70 variants across 23 candidate genes involved in sphingolipid-metabolizing pathways also demonstrate association (p = 10−4 or less). Circulating concentrations of several key components in sphingolipid metabolism are thus under strong genetic control, and variants in these loci can be tested for a role in the development of common cardiovascular, metabolic, neurological, and psychiatric diseases.
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| 42. |
- Jansen, Willemijn J, et al.
(författare)
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Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
- 2022
-
Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
-
Tidskriftsartikel (refereegranskat)abstract
- One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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| 43. |
- Katselis, D., et al.
(författare)
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On experiment design for single carrier and multicarrier systems
- 2015
-
Ingår i: 2015 European Control Conference, ECC 2015. - : Institute of Electrical and Electronics Engineers (IEEE). - 9783952426937 ; , s. 1772-1777
-
Konferensbidrag (refereegranskat)abstract
- In this paper, the problem of experiment design in single input single output (SISO) single carrier (SC) systems under a deterministic channel assumption is investigated and several connections with optimal preamble designs in multicarrier (MC) systems are established. In the context of SC systems, we derive optimal input sequences for the least-squares (LS) channel estimator under an input energy constraint. We then establish certain connections to optimal input designs for LS frequency domain channel estimation in MC systems. These connections reflect similarities between SC and MC systems both quantitative, i.e., in the achievable mean square error (MSE) performance, as well as qualitative, i.e., in the actual optimal input sequences. Simulations are provided to support the derived results.
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| 44. |
- Katselis, Dimitrios, et al.
(författare)
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On the end-performance metric estimator selection
- 2015
-
Ingår i: Automatica. - : Elsevier BV. - 0005-1098 .- 1873-2836. ; 58, s. 22-27
-
Tidskriftsartikel (refereegranskat)abstract
- It is well known that appropriately biasing an estimator can potentially lead to a lower mean square error (MSE) than the achievable MSE within the class of unbiased estimators. Nevertheless, the choice of an appropriate bias is generally unclear and only recently there have been attempts to systematize such a selection. These systematic approaches aim at introducing MSE bounds that are lower than the unbiased Cramer-Rao bound (CRB) for all values of the unknown parameters and at choosing biased estimators that beat the standard maximum-likelihood (ML) and/or least squares (LS) estimators in the finite sample case. In this paper, we take these approaches one step further and investigate the same problem from the aspect of an end-performance metric different than the classical MSE. This study is motivated by recent advances in the area of system identification indicating that the optimal experiment design Should be done by taking into account the end-performance metric of interest and not by quantifying a quadratic distance of the unknown model from the true one.
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| 45. |
- Kim, Min Seo, et al.
(författare)
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Comparative effectiveness of N95, surgical or medical, and non-medical facemasks in protection against respiratory virus infection: A systematic review and network meta-analysis
- 2022
-
Ingår i: Reviews in Medical Virology. - : WILEY. - 1052-9276 .- 1099-1654. ; 32:5
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Forskningsöversikt (refereegranskat)abstract
- The aim of this systematic review and network meta-analysis is to evaluate the comparative effectiveness of N95, surgical/medical and non-medical facemasks as personal protective equipment against respiratory virus infection. The study incorporated 35 published and unpublished randomized controlled trials and observational studies investigating specific mask effectiveness against influenza virus, SARS-CoV, MERS-CoV and SARS-CoV-2. We searched PubMed, Google Scholar and medRxiv databases for studies published up to 5 February 2021 (PROSPERO registration: CRD42020214729). The primary outcome of interest was the rate of respiratory viral infection. The quality of evidence was estimated using the GRADE approach. High compliance to mask-wearing conferred a significantly better protection (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.23-0.82) than low compliance. N95 or equivalent masks were the most effective in providing protection against coronavirus infections (OR, 0.30; CI, 0.20-0.44) consistently across subgroup analyses of causative viruses and clinical settings. Evidence supporting the use of medical or surgical masks against influenza or coronavirus infections (SARS, MERS and COVID-19) was weak. Our study confirmed that the use of facemasks provides protection against respiratory viral infections in general; however, the effectiveness may vary according to the type of facemask used. Our findings encourage the use of N95 respirators or their equivalents (e.g., P2) for best personal protection in healthcare settings until more evidence on surgical and medical masks is accrued. This study highlights a substantial lack of evidence on the comparative effectiveness of mask types in community settings.
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| 46. |
- Kontsevaya, Irina, et al.
(författare)
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Perspectives for systems biology in the management of tuberculosis
- 2021
-
Ingår i: European Respiratory Review. - : European Respiratory Society (ERS). - 0905-9180 .- 1600-0617. ; 30:160
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Forskningsöversikt (refereegranskat)abstract
- Standardised management of tuberculosis may soon be replaced by individualised, precision medicine-guided therapies informed with knowledge provided by the field of systems biology. Systems biology is a rapidly expanding field of computational and mathematical analysis and modelling of complex biological systems that can provide insights into mechanisms underlying tuberculosis, identify novel biomarkers, and help to optimise prevention, diagnosis and treatment of disease. These advances are critically important in the context of the evolving epidemic of drug-resistant tuberculosis. Here, we review the available evidence on the role of systems biology approaches - human and mycobacterial genomics and transcriptomics, proteomics, lipidomics/metabolomics, immunophenotyping, systems pharmacology and gut microbiomes - in the management of tuberculosis including prediction of risk for disease progression, severity of mycobacterial virulence and drug resistance, adverse events, comorbidities, response to therapy and treatment outcomes. Application of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach demonstrated that at present most of the studies provide "very low" certainty of evidence for answering clinically relevant questions. Further studies in large prospective cohorts of patients, including randomised clinical trials, are necessary to assess the applicability of the findings in tuberculosis prevention and more efficient clinical management of patients.
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| 47. |
- Köttgen, Anna, et al.
(författare)
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New loci associated with kidney function and chronic kidney disease
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:5, s. 376-384
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 individuals of European ancestry from 20 predominantly population-based studies in order to identify new susceptibility loci for reduced renal function as estimated by serum creatinine (eGFRcrea), serum cystatin c (eGFRcys) and CKD (eGFRcrea < 60 ml/min/1.73 m2; n = 5,807 individuals with CKD (cases)). Follow-up of the 23 new genome-wide–significant loci (P < 5 × 10−8) in 22,982 replication samples identified 13 new loci affecting renal function and CKD (in or near LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2, DACH1, UBE2Q2 and SLC7A9) and 7 loci suspected to affect creatinine production and secretion (CPS1, SLC22A2, TMEM60, WDR37, SLC6A13, WDR72 and BCAS3). These results further our understanding of the biologic mechanisms of kidney function by identifying loci that potentially influence nephrogenesis, podocyte function, angiogenesis, solute transport and metabolic functions of the kidney.
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| 48. |
- Lamperti, I., et al.
(författare)
-
SUPER: V. ALMA continuum observations of z ∼2 AGN and the elusive evidence of outflows influencing star formation
- 2021
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 654
-
Tidskriftsartikel (refereegranskat)abstract
- We study the impact of active galactic nuclei (AGN) ionised outflows on star formation in high-redshift AGN host galaxies, by combining near-infrared integral field spectroscopic (IFS) observations, mapping the H emission and [O iii]5007 outflows, with matched-resolution observations of the rest-frame far-infrared (FIR) emission.We present high-resolution ALMA Band 7 observations of eight X-ray selected AGN (L2-10 keV = 1043:81045:2 erg s1) at z 2 from the SUPER (SINFONI Survey for Unveiling the Physics and Eect of Radiative feedback) sample, targeting the observed-frame 870 m (rest-frame 260 m) continuum at 2 kpc (0.200) spatial resolution. The targets were selected among the SUPER AGN with an [O iii] detection in the IFS maps and with a detection in the FIR photometry. We detected six out of eight targets with signal-to-noise ratio S=N & 10 in the ALMA maps, from which we measured continuum flux densities in the range 0:272:58 mJy and FIR half-light radii (Re) in the range 0:8-2:1 kpc. The other two targets were detected with S/N of 3.6 and 5.9, which are insucient for spatially resolved analysis. The FIR Re of our sample are comparable to other AGN and star-forming galaxies at a similar redshift from the literature. However, combining our sample with the literature samples, we find that the mean FIR size in X-ray AGN (Re = 1:16 0:11 kpc) is slightly smaller than in non-AGN (Re = 1:69 0:13 kpc). From spectral energy distribution fitting, we find that the main contribution to the 260 m flux density is dust heated by star formation, with 4% contribution from AGN-heated dust and 1% from synchrotron emission. The majority of our sample show dierent morphologies for the FIR (mostly due to reprocessed stellar emission) and the ionised gas emission (H and [O iii], mostly due to AGN emission). This could be due to the dierent locations of dust and ionised gas, the dierent sources of the emission (stars and AGN), or the eect of dust obscuration.We are unable to identify any residual H emission, above that dominated by AGN, that could be attributed to star formation. Under the assumption that the FIR emission is a reliable tracer of obscured star formation, we find that the obscured star formation activity in these AGN host galaxies is not clearly aected by the ionised outflows. However, we cannot rule out that star formation suppression is happening on smaller spatial scales than the ones we probe with our observations (<2 kpc) or on dierent timescales.
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| 49. |
- Lazaridis, Iosif, et al.
(författare)
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Ancient human genomes suggest three ancestral populations for present-day Europeans
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 513:7518, s. 409-
-
Tidskriftsartikel (refereegranskat)abstract
- We sequenced the genomes of a similar to 7,000-year-old farmer from Germany and eight similar to 8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes(1-4) with 2,345 contemporary humans to show that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians(3), who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations' deep relationships and show that early European farmers had similar to 44% ancestry from a 'basal Eurasian' population that split before the diversification of other non-African lineages.
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| 50. |
- Liga, Gabriele, et al.
(författare)
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Ultra-Wideband Nonlinearity Compensation Performance in the Presence of PMD
- 2016
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Ingår i: 42nd European Conference on Optical Communication, ECOC 2016; Dusseldorf; Germany; 18 September 2016 through 22 September 2016. - 9783800742745 ; , s. 794-796
-
Konferensbidrag (refereegranskat)abstract
- We investigate the performance of multi-channel digital backpropagation for 1 THz bandwidth optical fibre transmission in the presence of polarisation-mode dispersion. We show that the average SNR performance rapidly saturates as a function of the compensation bandwidth.
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