| 1. |
- 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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| 2. |
- Plompen, A. J. M., et al.
(författare)
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The joint evaluated fission and fusion nuclear data library, JEFF-3.3
- 2020
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Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 56:7
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Forskningsöversikt (refereegranskat)abstract
- The joint evaluated fission and fusion nuclear data library 3.3 is described. New evaluations for neutron-induced interactions with the major actinides 235U, 238U and 239Pu, on 241Am and 23Na, 59Ni, Cr, Cu, Zr, Cd, Hf, W, Au, Pb and Bi are presented. It includes new fission yields, prompt fission neutron spectra and average number of neutrons per fission. In addition, new data for radioactive decay, thermal neutron scattering, gamma-ray emission, neutron activation, delayed neutrons and displacement damage are presented. JEFF-3.3 was complemented by files from the TENDL project. The libraries for photon, proton, deuteron, triton, helion and alpha-particle induced reactions are from TENDL-2017. The demands for uncertainty quantification in modeling led to many new covariance data for the evaluations. A comparison between results from model calculations using the JEFF-3.3 library and those from benchmark experiments for criticality, delayed neutron yields, shielding and decay heat, reveals that JEFF-3.3 performes very well for a wide range of nuclear technology applications, in particular nuclear energy.
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| 3. |
- van Hilst, Jony, et al.
(författare)
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Minimally invasive versus open distal pancreatectomy for pancreatic ductal adenocarcinoma (DIPLOMA) : study protocol for a randomized controlled trial
- 2021
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Ingår i: Trials. - : BMC. - 1745-6215. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recently, the first randomized trials comparing minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) for non-malignant and malignant disease showed a 2-day reduction in time to functional recovery after MIDP. However, for pancreatic ductal adenocarcinoma (PDAC), concerns have been raised regarding the oncologic safety (i.e., radical resection, lymph node retrieval, and survival) of MIDP, as compared to ODP. Therefore, a randomized controlled trial comparing MIDP and ODP in PDAC regarding oncological safety is warranted. We hypothesize that the microscopically radical resection (R0) rate is non-inferior for MIDP, as compared to ODP. Methods/design: DIPLOMA is an international randomized controlled, patient- and pathologist-blinded, non-inferiority trial performed in 38 pancreatic centers in Europe and the USA. A total of 258 patients with an indication for elective distal pancreatectomy with splenectomy because of proven or highly suspected PDAC of the pancreatic body or tail will be randomly allocated to MIDP (laparoscopic or robot-assisted) or ODP in a 1:1 ratio. The primary outcome is the microscopically radical resection margin (R0, distance tumor to pancreatic transection and posterior margin >= 1 mm), which is assessed using a standardized histopathology assessment protocol. The sample size is calculated with the following assumptions: 5% one-sided significance level (alpha), 80% power (1-beta), expected R0 rate in the open group of 58%, expected R0 resection rate in the minimally invasive group of 67%, and a non-inferiority margin of 7%. Secondary outcomes include time to functional recovery, operative outcomes (e.g., blood loss, operative time, and conversion to open surgery), other histopathology findings (e.g., lymph node retrieval, perineural- and lymphovascular invasion), postoperative outcomes (e.g., clinically relevant complications, hospital stay, and administration of adjuvant treatment), time and site of disease recurrence, survival, quality of life, and costs. Follow-up will be performed at the outpatient clinic after 6, 12, 18, 24, and 36 months postoperatively. Discussion: The DIPLOMA trial is designed to investigate the non-inferiority of MIDP versus ODP regarding the microscopically radical resection rate of PDAC in an international setting.
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| 4. |
- Coquery, N, et al.
(författare)
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Locomotion and eating behavior changes in Yucatan minipigs after unilateral radio-induced ablation of the caudate nucleus
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 17082-
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Tidskriftsartikel (refereegranskat)abstract
- The functional roles of the Caudate nucleus (Cd) are well known. Selective Cd lesions can be found in neurological disorders. However, little is known about the dynamics of the behavioral changes during progressive Cd ablation. Current stereotactic radiosurgery technologies allow the progressive ablation of a brain region with limited adverse effects in surrounding normal tissues. This could be of high interest for the study of the modified behavioral functions in relation with the degree of impairment of the brain structures. Using hypofractionated stereotactic radiotherapy combined with synchrotron microbeam radiation, we investigated, during one year after irradiation, the effects of unilateral radio-ablation of the right Cd on the behavior of Yucatan minipigs. The right Cd was irradiated to a minimal dose of 35.5 Gy delivered in three fractions. MRI-based morphological brain integrity and behavioral functions, i.e. locomotion, motivation/hedonism were assessed. We detected a progressive radio-necrosis leading to a quasi-total ablation one year after irradiation, with an additional alteration of surrounding areas. Transitory changes in the motivation/hedonism were firstly detected, then on locomotion, suggesting the influence of different compensatory mechanisms depending on the functions related to Cd and possibly some surrounding areas. We concluded that early behavioral changes related to eating functions are relevant markers for the early detection of ongoing lesions occurring in Cd-related neurological disorders.
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| 5. |
- Moens, Annick, et al.
(författare)
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Pregnancy outcomes in inflammatory bowel disease patients treated with vedolizumab, anti-TNF or conventional therapy : results of the European CONCEIVE study
- 2020
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Blackwell Publishing. - 0269-2813 .- 1365-2036. ; 51:1, s. 129-138
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Tidskriftsartikel (refereegranskat)abstract
- Background: Women with inflammatory bowel diseases (IBD) often receive biologicals during pregnancy to maintain disease remission. Data on outcome of vedolizumab-exposed pregnancies (VDZE) are sparse.Aims: The aim was to assess pregnancy and child outcomes of VDZE pregnancies and to compare these results to anti-TNF exposed (TNFE) or both immunomodulatory and biologic unexposed (CON IBD) pregnancies.Methods: A retrospective multicentre case-control observational study was performed.Results: VDZE group included 79 pregnancies in 73 IBD women. The TNFE and CON IBD group included 186 pregnancies (162 live births) in 164 IBD women and 184 pregnancies (163 live births) in 155 IBD women, respectively. At conception, cases more often had active disease ([VDZE: 36% vs TNFE: 17%, P = .002] and [VDZE: 36% vs CON IBD: 24%, P = .063]). No significant difference in miscarriage rates were found between groups (VDZE and TNFE: 16% vs 13%, P = .567; VDZE and CON IBD: 16% vs 10%, P = .216). In live-born infants, median gestational age and birthweight were similar between groups. Median Apgar score at birth was numerically equal. Prematurity was similar in the VDZE group compared to the control groups, even when correcting for disease activity during pregnancy. The frequency of congenital anomalies was comparable between groups as were the percentages of breastfed babies. During the first year of life, no malignancies were reported and infants' infection risk did not significantly differ between groups.Conclusion: No new safety signal was detected in VDZE pregnancies although larger, prospective studies are required for confirmation.
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| 6. |
- Kumar, Dinesh, et al.
(författare)
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Nuclear data adjustment using Bayesian inference, diagnostics for model fit and influence of model parameters
- 2020
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Ingår i: ND 2019. - : EDP Sciences. - 9782759891061
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Konferensbidrag (refereegranskat)abstract
- The mathematical models used for nuclear data evaluations contain a large number of theoretical parameters that are usually uncertain. These parameters can be calibrated (or improved) by the information collected from integral/differential experiments. The Bayesian inference technique is used to utilize measurements for data assimilation. The Bayesian approximation is based on the least-square or Monte-Carlo approaches. In this process, the model parameters are optimized In the adjustment process, it is essential to include the analysis related to the influence of model parameters on the adjusted data. In this work, some statistical indicators such as the concept of Cook's distance; Akaike, Bayesian and deviance information criteria; effective degrees of freedom are developed within the CONRAD platform. Further, these indicators are applied to a test case of Gd-155 to evaluate and compare the influence of resonance parameters.
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| 7. |
- Noguere, G., et al.
(författare)
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Doppler broadening of neutron-induced resonances using ab initio phonon spectrum
- 2018
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Ingår i: The European Physical Journal Plus. - : Springer Berlin/Heidelberg. - 2190-5444. ; 133:5
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Tidskriftsartikel (refereegranskat)abstract
- Neutron resonances observed in neutron cross section data can only be compared with their theoretical analogues after a correct broadening of the resonance widths. This broadening is usually carried out by two different theoretical models, namely the Free Gas Model and the Crystal Lattice Model, which, however, are only applicable under certain assumptions. Here, we use neutron transmission experiments on UO2 samples at T = 23.7 K and T = 293.7 K, to investigate the limitations of these models when an ab initio phonon spectrum is introduced in the calculations. Comparisons of the experimental and theoretical transmissions highlight the underestimation of the energy transferred at low temperature and its impact on the accurate determination of the radiation widths Gamma(gamma lambda) of the U-238 resonances lambda. The observed deficiency of the model represents an experimental evidence that the Debye-Waller factor is not correctly calculated at low temperature near the Neel temperature (T-N = 30.8 K).
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