| 1. |
- Aad, G, et al.
(author)
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- 2015
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swepub:Mat__t
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| 2. |
- Wessel, Jennifer, et al.
(author)
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Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
- 2015
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Journal article (peer-reviewed)abstract
- Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
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| 3. |
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| 4. |
- Pattaro, Cristian, et al.
(author)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)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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| 5. |
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| 6. |
- Huffman, Jennifer E., et al.
(author)
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Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans
- 2015
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:3
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Journal article (peer-reviewed)abstract
- We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, P-inter= 2.6 x 10(-8)). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDAR-ADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 x 10(-8)), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 10(-8)), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (Pdifflean-obese= 2 x 10(-4)). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment.
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| 7. |
- Lin, C., et al.
(author)
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Study on probabilistic mean features of lower and upper free-surface profiles and velocity fields of a highly fluctuating free jet over a chute
- 2018
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In: Journal of Marine Science and Technology (Taiwan). - : National Taiwan Ocean University. - 1023-2796. ; 26:3, s. 309-326
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Journal article (peer-reviewed)abstract
- An optic-based method that utilizes the particle-laden images captured during high-speed particle image velocimetry (HSPIV) measurements is presented, aiming to explore the probabilistic mean characteristics of the free surface profiles and velocity fields of a free jet with high-frequency random fluctuations over a chute. The technique based on the gray-level gradients in the smoothed gray level distribution of the contrast-enhanced images is used to determine the probabilistic mean features of the free jet, right beneath and above which the water-air interfaces have I%/(100 I)% intermittent appearance of air/water phase and (100 I)% /I% fitful show-up of water/air phase. Further, the cross-correlation calculation for HSPIV measurements is employed to obtain the instantaneous and probabilistic mean velocity fields of the free jet. A target experiment of the free jet having a mean water-depth of 2.76 cm and a Froude number of 3.92 over a 17 chute model is performed in a re-circulating water channel to demonstrate the application of this method. The entire process for obtaining the probabilistic mean positions of the free surface profiles is elucidated step-by step. The lower/upper part of the free surface changing from the height at which the possibility of intermittent appearance of water phase is 3%/97%, via the counterpart for 50%/50%, to that for 97%/ 3% is identified precisely. In addition, the probabilistic mean velocity field is further categorized into the conditionally and overall time-averaged ones. Each streamwise velocity profile in the conditionally time-averaged velocity field is fairly uniform. However, the counterpart in the overall time-averaged velocity field evidently shows the non-uniform feature with prominent velocity gradient in the lower/upper part between the height at which the possibility of intermittent appearance of water phase is 3%/97% and the counterpart is 97%/3%.
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| 8. |
- Lin, C., et al.
(author)
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Velocity characteristics in boundary layer flow caused by solitary wave traveling over horizontal bottom
- 2016
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In: Experimental Thermal and Fluid Science. - : Elsevier. - 0894-1777 .- 1879-2286. ; 76, s. 238-252
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Journal article (peer-reviewed)abstract
- The characteristics of horizontal velocity in the bottom boundary-layer flow induced by a solitary wave propagating over a horizontal bottom are presented experimentally, using high-speed particle image velocimetry (HSPIV). The ratio of wave height to water depth varies from 0.096 to 0.386 and the flow inside the boundary layer is laminar. The results show that the horizontal velocity profiles can be mainly classified into two categories with respect to the passing of the solitary wave-crest at the measuring section: the pre-passing (or acceleration) phases under favorable pressure gradient and post-passing (or deceleration) phases under adverse pressure gradient. For the velocity distributions obtained during the pre-passing phases, a nonlinear regression analysis was used to precisely determine the time-dependent characteristic length and velocity scales underlying these profiles. A similarity profile of the horizontal velocity is established first using the time-dependent free-stream velocity and boundary layer thickness as the characteristic velocity and length scales, respectively. In addition, the displacement thickness, the momentum thickness, and the energy thickness are also considered as alternative length scales. All these four representative thicknesses are closely related to each other, demonstrating that any one amongst them can be regarded as the characteristic length scale. The forms of similarity profiles for the non-dimensional velocity distributions are somewhat analogous to the results of steady boundary layer flow over a thin plate under with pressure gradient, but with different coefficients or powers. While during the post-passing phases, flow reversal which acts like an unsteady wall jet and moves in the opposite direction against the wave propagation occurs after the passage of solitary wave-crest. The thickness of flow reversal layer increases with time. A similarity profile is proposed for the velocity distributions corresponding to occurrence of the extreme value in the maximum negative velocity of flow reversal. Variations of the maximum negative velocity and the thickness of flow reversal with the time right after the start of flow reversal are also discussed in detail. Moreover, the non-dimensional time leads of the horizontal velocities at different heights in the boundary layer over the free-stream velocity are evidenced to be more noticeable toward the bottom, and also in lower ratio of wave height to water depth. A similarity profile for the non-dimensional time lead versus the non-dimensional height above the bottom surface is also presented.
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| 9. |
- Loeffen, Erik A. H., et al.
(author)
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Reducing pain in children with cancer : Methodology for the development of a clinical practice guideline
- 2019
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In: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 66:6
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Journal article (peer-reviewed)abstract
- Although pain is one of the most prevalent and bothersome symptoms children with cancer experience, evidence-based guidance regarding assessment and management is lacking. With 44 international, multidisciplinary healthcare professionals and nine patient representatives, we aimed to develop a clinical practice guideline (following GRADE methodology), addressing assessment and pharmacological, psychological, and physical management of tumor-, treatment-, and procedure-related pain in children with cancer. In this paper, we present our thorough methodology for this development, including the challenges we faced and how we approached these. This lays the foundation for our clinical practice guideline, for which there is a high clinical demand.
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| 10. |
- Peña Fernández, Marta, et al.
(author)
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Preservation of Bone Tissue Integrity with Temperature Control for In Situ SR-MicroCT Experiments.
- 2018
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In: Materials. - : MDPI AG. - 1996-1944. ; 11:11
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Journal article (peer-reviewed)abstract
- Digital volume correlation (DVC), combined with in situ synchrotron microcomputed tomography (SR-microCT) mechanics, allows for 3D full-field strain measurement in bone at the tissue level. However, long exposures to SR radiation are known to induce bone damage, and reliable experimental protocols able to preserve tissue properties are still lacking. This study aims to propose a proof-of-concept methodology to retain bone tissue integrity, based on residual strain determination using DVC, by decreasing the environmental temperature during in situ SR-microCT testing. Compact and trabecular bone specimens underwent five consecutive full tomographic data collections either at room temperature or 0 °C. Lowering the temperature seemed to reduce microdamage in trabecular bone but had minimal effect on compact bone. A consistent temperature gradient was measured at each exposure period, and its prolonged effect over time may induce localised collagen denaturation and subsequent damage. DVC provided useful information on irradiation-induced microcrack initiation and propagation. Future work is necessary to apply these findings to in situ SR-microCT mechanical tests, and to establish protocols aiming to minimise the SR irradiation-induced damage of bone.
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