| 1. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 2. |
- Dyke, Stephanie O M, et al.
(författare)
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Epigenome data release : a participant-centered approach to privacy protection
- 2015
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Large-scale epigenome mapping by the NIH Roadmap Epigenomics Project, the ENCODE Consortium and the International Human Epigenome Consortium (IHEC) produces genome-wide DNA methylation data at one base-pair resolution. We examine how such data can be made open-access while balancing appropriate interpretation and genomic privacy. We propose guidelines for data release that both reduce ambiguity in the interpretation of open-access data and limit immediate access to genetic variation data that are made available through controlled access.
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| 3. |
- Paul, Dirk S., et al.
(författare)
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Increased DNA methylation variability in type 1 diabetes across three immune effector cell types
- 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
- The incidence of type 1 diabetes (T1D) has substantially increased over the past decade, suggesting a role for non-genetic factors such as epigenetic mechanisms in disease development. Here we present an epigenome-wide association study across 406,365 CpGs in 52 monozygotic twin pairs discordant for T1D in three immune effector cell types. We observe a substantial enrichment of differentially variable CpG positions (DVPs) in T1D twins when compared with their healthy co-twins and when compared with healthy, unrelated individuals. These T1D-associated DVPs are found to be temporally stable and enriched at gene regulatory elements. Integration with cell type-specific gene regulatory circuits highlight pathways involved in immune cell metabolism and the cell cycle, including mTOR signalling. Evidence from cord blood of newborns who progress to overt T1D suggests that the DVPs likely emerge after birth. Our findings, based on 772 methylomes, implicate epigenetic changes that could contribute to disease pathogenesis in T1D.
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| 4. |
- Raval, Aparna, et al.
(författare)
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Downregulation of death-associated protein kinase 1 (DAPK1) in chronic lymphocytic leukemia
- 2007
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 129:5, s. 879-890
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Tidskriftsartikel (refereegranskat)abstract
- The heritability of B cell chronic lymphocytic leukemia (CLL) is relatively high; however, no predisposing mutation has been convincingly identified. We show that loss or reduced expression of death-associated protein kinase 1 (DAPK1) underlies cases of heritable predisposition to CLL and the majority of sporadic CLL. Epigenetic silencing of DAPK1 by promoter methylation occurs in almost all sporadic CLL cases. Furthermore, we defined a disease haplotype, which segregates with the CLL phenotype in a large family. DAPK1 expression of the CLL allele is downregulated by 75% in germline cells due to increased HOXB7 binding. In the blood cells from affected family members, promoter methylation results in additional loss of DAPK1 expression. Thus, reduced expression of DAPK1 can result from germline predisposition, as well as epigenetic or somatic events causing or contributing to the CLL phenotype.
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| 5. |
- Abdelhalim, Mohamed A., et al.
(författare)
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Multicenter trans-Atlantic experience with fenestrated-branched endovascular aortic repair of chronic post-dissection thoracoabdominal aortic aneurysms
- 2023
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Ingår i: Journal of Vascular Surgery. - : Elsevier. - 0741-5214 .- 1097-6809. ; 78:4, s. 854-862.e1
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: This multicenter international study aimed to describe outcomes of fenestrated-branched endovascular aortic repairs (FB-EVAR) in a cohort of patients treated for chronic post-dissection thoracoabdominal aortic aneurysms (PD-TAAAs).METHODS: We reviewed the clinical data of all consecutive patients treated by FB-EVAR for repair of extent I to III PD-TAAAs in 16 centers from the United States and Europe (2008-2021). Data were extracted from institutional prospectively maintained databases and electronic patient records. All patients received off-the-shelf or patient-specific manufactured fenestrated-branched stent grafts. Endpoints were any cause mortality and major adverse events at 30 days, technical success, target artery (TA) patency, freedom from TA instability, minor (endovascular with <12 Fr sheath) and major (open or ≥12 Fr sheath) secondary interventions, patient survival, and freedom from aortic-related mortality (ARM).RESULTS: A total of 246 patients (76% male; median age, 67 years [interquartile range, 61-73 years]) were treated for extent I (7%), extent II (55%), and extent III (35%) PD-TAAAs by FB-EVAR. The median aneurysm diameter was 65 mm (interquartile range, 59-73 mm). Eighteen patients (7%) were octogenarians, 212 (86%) were American Society of Anesthesiologists class ≥3, and 21 (9%) presented with contained ruptured or symptomatic aneurysms. There were 917 renal-mesenteric vessels targeted by 581 fenestrations (63%) and 336 directional branches (37%), with a mean of 3.7 vessels per patient. Technical success was 96%. Mortality and rate of major adverse events at 30 days was 3% and 28%, including disabling complications such as new onset dialysis in 1%, major stroke in 1%, and permanent paraplegia in 2%. Mean follow-up was 24 months. Kaplan-Meier (KM) estimated patient survival at 3 and 5 years was 79% ± 6% and 65% ± 10%. KM estimated freedom from ARM was 95% ± 3% and 93% ± 5% at the same intervals. Unplanned secondary interventions were needed in 94 patients (38%), including minor procedures in 64 (25%) and major procedures in 30 (12%). There was one conversion to open surgical repair (<1%). KM estimated freedom from any secondary intervention was 44% ± 9% at 5 years. KM estimated primary and secondary TA patency were 93% ± 2% and 96% ± 1% at 5 years, respectively.CONCLUSIONS: FB-EVAR for chronic PD-TAAAs was associated with high technical success and a low rate of mortality (3%) and disabling complications at 30 days. Although the procedure is effective in the prevention of ARM, patient survival was low at 5 years (65%), likely due to the significant comorbidities in this cohort of patients. Freedom from secondary interventions at 5 years was 44%, although most procedures were minor. The significant rate of reinterventions highlights the need for continued patient surveillance.
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| 6. |
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| 7. |
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| 8. |
- Budin-Ljosne, Isabelle, et al.
(författare)
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Dynamic Consent : a potential solution to some of the challenges of modern biomedical research
- 2017
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Ingår i: BMC Medical Ethics. - : Springer Science and Business Media LLC. - 1472-6939. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Innovations in technology have contributed to rapid changes in the way that modern biomedical research is carried out. Researchers are increasingly required to endorse adaptive and flexible approaches to accommodate these innovations and comply with ethical, legal and regulatory requirements. This paper explores how Dynamic Consent may provide solutions to address challenges encountered when researchers invite individuals to participate in research and follow them up over time in a continuously changing environment. Methods: An interdisciplinary workshop jointly organised by the University of Oxford and the COST Action CHIP ME gathered clinicians, researchers, ethicists, lawyers, research participants and patient representatives to discuss experiences of using Dynamic Consent, and how such use may facilitate the conduct of specific research tasks. The data collected during the workshop were analysed using a content analysis approach. Results: Dynamic Consent can provide practical, sustainable and future-proof solutions to challenges related to participant recruitment, the attainment of informed consent, participant retention and consent management, and may bring economic efficiencies. Conclusions: Dynamic Consent offers opportunities for ongoing communication between researchers and research participants that can positively impact research. Dynamic Consent supports inter-sector, cross-border approaches and large scale data-sharing. Whilst it is relatively easy to set up and maintain, its implementation will require that researchers re-consider their relationship with research participants and adopt new procedures.
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| 9. |
- Butorin, Sergei, et al.
(författare)
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Effect of carbon content on electronic structure of uranium carbides
- 2023
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- The electronic structure of UCx (x = 0.9, 1.0, 1.1, 2.0) was studied by means of x-ray absorption spectroscopy (XAS) at the CK edge and measurements in the high energy resolution fluorescence detection (HERFD) mode at the U M-4 and L-3 edges. The full-relativistic density functional theory calculations taking into account the 5f - 5f Coulomb interaction U and spin-orbit coupling (DFT+U+SOC) were also performed for UCand UC2. While the U L-3 HERFD-XAS spectra of the studied samples reveal little difference, the U M-4 HERFD-XAS spectra show certain sensitivity to the varying carbon content in uranium carbides. The observed gradual changes in the U M-4 HERFD spectra suggest an increase in the C2p-U 5f charge transfer, which is supported by the orbital population analysis in the DFT+U+ SOC calculations, indicating an increase in the U 5f occupancy in UC2 as compared to that in UC. On the other hand, the density of states at the Fermi level were found to be significantly lower in UC2, thus affecting the thermodynamic properties. Both the x-ray spectroscopic data (in particular, the CK XAS measurements) and results of the DFT+U+SOC calculations indicate the importance of taking into account U and SOC for the description of the electronic structure of actinide carbides.
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| 10. |
- Butorin, Sergei, et al.
(författare)
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X-ray spectroscopic study of chemical state in uranium carbides
- 2022
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Ingår i: Journal of Synchrotron Radiation. - : International Union of Crystallography (IUCr). - 0909-0495 .- 1600-5775. ; 29, s. 295-302
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Tidskriftsartikel (refereegranskat)abstract
- UC and UMeC2 (Me = Fe, Zr, Mo) carbides were studied by the high-energyresolution fluorescence-detected X-ray absorption (HERFD-XAS) technique at the U M-4 and L-3 edges. Both U M-4 and L-3 HERFD-XAS reveal some differences between UMeC2 and UC; there are differences also between the M-4 and L-3 edge results for both types of carbide in terms of the spectral width and energy position. The observed differences are attributed to the consequences of the U 5f, 6d-4d(3d) hybridization in UMeC2. Calculations of the U M-4 HERFD-XAS spectra were also performed using the Anderson impurity model (AIM). Based on the analysis of the data, the 5f occupancy in the ground state of UC was estimated to be 3.05 electrons. This finding is also supported by the analysis of U N-4,N-5 XAS of UC and by the results of the AIM calculations of the U 4f X-ray photoelectron spectrum of UC.
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| 11. |
- Cardona, Alexia, et al.
(författare)
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Epigenome-wide association study of incident type 2 diabetes in a British population : EPIC-Norfolk study
- 2019
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 68:12, s. 2315-2326
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Tidskriftsartikel (refereegranskat)abstract
- Epigenetic changes may contribute substantially to risks of diseases of aging. Previous studies reported seven methylation variable positions (MVPs) robustly associated with incident type 2 diabetes mellitus (T2DM). However, their causal roles in T2DM are unclear. In an incident T2DM case-cohort study nested within the populationbased European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort, we used whole blood DNA collected at baseline, up to 11 years before T2DM onset, to investigate the role of methylation in the etiology of T2DM. We identified 15 novel MVPs with robust associations with incident T2DM and robustly confirmed three MVPs identified previously (near to TXNIP, ABCG1, and SREBF1). All 18 MVPs showed directionally consistent associations with incident and prevalent T2DM in independent studies. Further conditional analyses suggested that the identified epigenetic signals appear related to T2DM via glucose and obesityrelated pathways acting before the collection of baseline samples.We integrated genome-wide genetic data to identify methylation-associated quantitative trait loci robustly associated with 16 of the 18 MVPs and found one MVP, cg00574958 at CPT1A, with a possible direct causal role in T2DM. None of the implicated genes were previously highlighted by genetic association studies, suggesting that DNA methylation studies may reveal novel biological mechanisms involved in tissue responses to glycemia.
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| 12. |
- Carén, Helena, 1979, et al.
(författare)
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Differentiation therapy for glioblastoma - too many obstacles?
- 2016
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Ingår i: Molecular & cellular oncology. - : Informa UK Limited. - 2372-3556. ; 3:2
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Forskningsöversikt (refereegranskat)abstract
- The therapeutic potential of differentiation therapy for glioblastoma will depend on the robustness and stability of the differentiated state. We recently reported several obstacles to bone morphogenetic protein (BMP)-induced differentiation therapy. Improved understanding of the mechanisms that tumor cells use to escape differentiation commitment is urgently needed.
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| 13. |
- Dias, N., et al.
(författare)
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Outcomes of Elective and Non-elective Fenestrated-branched Endovascular Aortic Repair for Treatment of Thoracoabdominal Aortic Aneurysms
- 2023
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Ingår i: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 278:4, s. 568-577, s. 568-577
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe outcomes after elective and non-elective fenestrated-branched endovascular aortic repair (FB-EVAR) for thoracoabdominal aortic aneurysms (TAAAs).Background: FB-EVAR has been increasingly utilized to treat TAAAs; however, outcomes after non-elective versus elective repair are not well described.Methods: Clinical data of consecutive patients undergoing FB-EVAR for TAAAs at 24 centers (2006-2021) were reviewed. Endpoints including early mortality and major adverse events (MAEs), all-cause mortality, and aortic-related mortality (ARM), were analyzed and compared in patients who had non-elective versus elective repair.Results: A total of 2603 patients (69% males; mean age 72 +/- 10 year old) underwent FB-EVAR for TAAAs. Elective repair was performed in 2187 patients (84%) and non-elective repair in 416 patients [16%; 268 (64%) symptomatic, 148 (36%) ruptured]. Non-elective FB-EVAR was associated with higher early mortality (17% vs 5%, P < 0.001) and rates of MAEs (34% vs 20%, P < 0.001). Median follow-up was 15 months ( interquartile range, 7-37 months). Survival and cumulative incidence of ARM at 3 years were both lower for non-elective versus elective patients (50 +/- 4% vs 70 +/- 1% and 21 +/- 3% vs 7 +/- 1%, P < 0.001). On multivariable analysis, non-elective repair was associated with increased risk of all-cause mortality ( hazard ratio, 1.92; 95% CI] 1.50-2.44; P < 0.001) and ARM (hazard ratio, 2.43; 95% CI, 1.63-3.62; P < 0.001).Conclusions: Non-elective FB-EVAR of symptomatic or ruptured TAAAs is feasible, but carries higher incidence of early MAEs and increased all-cause mortality and ARM than elective repair. Long-term follow-up is warranted to justify the treatment.
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| 14. |
- Dias-Neto, Marina, et al.
(författare)
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Comparison of single- and multistage strategies during fenestrated-branched endovascular aortic repair of thoracoabdominal aortic aneurysms
- 2023
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Ingår i: Journal of Vascular Surgery. - : MOSBY-ELSEVIER. - 0741-5214 .- 1097-6809. ; 77:6, s. 1588-1597
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to compare outcomes of single or multistage approach during fenestrated-branched endovascular aortic repair (FB-EVAR) of extensive thoracoabdominal aortic aneurysms (TAAAs).Methods: We reviewed the clinical data of consecutive patients treated by FB-EVAR for extent I to III TAAAs in 24 centers (2006-2021). All patients received a single brand manufactured patient-specific or off-the-shelf fenestrated-branched stent grafts. Staging strategies included proximal thoracic aortic repair, minimally invasive segmental artery coil embolization, temporary aneurysm sac perfusion and combinations of these techniques. Endpoints were analyzed for elective repair in patients who had a single-or multistage approach before and after propensity score adjustment for baseline differences, including the composite 30-day/in-hospital mortality and/or permanent paraplegia, major adverse event, patient survival, and freedom from aortic-related mortality.Results: A total of 1947 patients (65% male; mean age, 71 +/- 8 years) underwent FB-EVAR of 155 extent I (10%), 729 extent II (46%), and 713 extent III TAAAs (44%). A single-stage approach was used in 939 patients (48%) and a multistage approach in 1008 patients (52%). A multistage approach was more frequently used in patients undergoing elective compared with non-elective repair (55% vs 35%; P < .001). Staging strategies were proximal thoracic aortic repair in 743 patients (74%), temporary aneurysm sac perfusion in 128 (13%), minimally invasive segmental artery coil embolization in 10 (1%), and combinations in 127 (12%). Among patients undergoing elective repair (n = 1597), the composite endpoint of 30-day/in-hospital mortality and/or permanent paraplegia rate occurred in 14% of single-stage and 6% of multistage approach patients (P < .001). After adjustment with a propensity score, multistage approach was associated with lower rates of 30-day/in-hospital mortality and/or permanent paraplegia (odds ratio, 0.466; 95% confidence interval, 0.271-0.801; P = .006) and higher patient survival at 1 year (86.9 +/- 1.3% vs 79.6 +/- 1.7%) and 3 years (72.7 +/- 2.1% vs 64.2 +/- 2.3%; adjusted hazard ratio, 0.714; 95% confidence interval, 0.528-0.966; P = .029), compared with a single stage approach.Conclusions: Staging elective FB-EVAR of extent I to III TAAAs was associated with decreased risk of mortality and/or permanent paraplegia at 30 days or within hospital stay, and with higher patient survival at 1 and 3 years.
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| 15. |
- Kling, Teresia, 1985, et al.
(författare)
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Validation of the MethylationEPIC BeadChip for fresh-frozen and formalin-fixed paraffin-embedded tumours.
- 2017
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Ingår i: Clinical epigenetics. - : Springer Science and Business Media LLC. - 1868-7083 .- 1868-7075. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- DNA methylation is the most studied epigenetic modification due to its role in regulating gene expression, and its involvement in the pathogenesis of cancer and several diseases upon aberrations in methylation. The method of choice to evaluate genome-wide methylation has been the Illumina HumanMethylation450 BeadChip (450K), but it was recently replaced with the MethylationEPIC BeadChip (EPIC). We therefore sought to validate the EPIC array in comparison to the 450K array for both fresh-frozen (FF) and formalin-fixed paraffin-embedded (FFPE) tumours. We also performed analysis on the EPIC array with paired FF and FFPE samples to adapt to a clinical setting where FFPE is routinely used. Further, we compared two restoration methods, REPLI-g and Infinium, for FFPE-derived DNA on the EPIC array. The Pearson correlation of β values for common probes on the 450K and EPIC array was high for both FF (mean: 0.992) and FFPE (mean: 0.984) samples. The β values generated from the EPIC array for FFPE samples correlated well with the paired FF tumours, but varied between 0.901 and 0.987. We did note that sample pairs with lower correlation had less bimodal density distributions of β values and displayed higher noise in the copy number alteration plots (generated from the methylation array data) in the FFPE sample. Both REPLI-g and the Infinium restoration for FFPE samples performed well on the EPIC array and generated equivalent correlation scores to the paired FF sample.
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| 16. |
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| 17. |
- Mardor, Israel, et al.
(författare)
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Determining spontaneous fission properties by direct mass measurements with the FRS Ion Catcher
- 2020
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Ingår i: ND 2019. - : EDP Sciences. - 9782759891061
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Konferensbidrag (refereegranskat)abstract
- We present a direct method to measure fission product yield distributions (FPY) and isomeric yield ratios (IYR) for spontaneous fission (SF) fragments. These physical properties are of utmost importance to the understanding of basic nuclear physics, the astrophysical rapid neutron capture process ('r process') of nucle-osynthesis, neutron star composition, and nuclear reactor safety. With this method, fission fragments are produced by spontaneous fission from a source that is mounted in a cryogenic stopping cell (CSC), thermalized and stopped within it, and then extracted and transported to a multiple-reflection time-of-flight mass-spectrometer (MR-TOF-MS). We will implement the method at the FRS Ion Catcher (FRS-IC) at GSI (Germany), whose MR-TOF-MS relative mass accuracy (similar to 10(-7)) and resolving power (similar to 600,000 FWHM) are sufficient to separate all isobars and numerous isomers in the fission fragment realm. The system's essential element independence and its fast simultaneous mass measurement provide a new direct way to measure isotopic FPY distributions, which is complementary to existing methods. It will enable nuclide FPY measurements in the high fission peak, which is hardly accessible by current techniques. The extraction time of the CSC, tens of milliseconds, enables a direct measurement of independent fission yields, and a first study of the temporal dependence of FPY distributions in this duration range. The ability to resolve isomers will further enable direct extraction of numerous IYRs while performing the FPY measurements. The method has been recently demonstrated at the FRS-ICr for SF with a 37 kBq Cf-252 fission source, where about 70 different fission fragments have been identified and counted. In the near future, it will be used for systematic studies of SF with a higher-activity Cf-252 source and a Cm-248 source. The method can be implemented also for neutron induced fission at appropriate facilities.
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| 18. |
- Mutarindwa, Samuel
(författare)
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Institutions, regulations, performance and stability of African banks
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis consists of four independent papers preceded by the introductory chapter linked through the thesis title. The first two papers focus on determinants of bank stability, while the other two focus on the determinants of bank performance.Paper one assesses the effects of bank compliance with Basel III liquidity and capital requirements on lending and stability. African banks complying with the liquidity threshold above median lend more but are less stable. However, banks above the median capital requirement are more stable but lend less. Compliance depend on central banks’ supervision, regulatory quality, and legal systems.Paper two investigates how legal systems and institutions influence central banks’ provision of supervisory guidance on corporate governance, and via this channel, affect governance and stability of banks. The publication of supervisory guidance on corporate governance helps banks to improve internal governance and stability, conditional on countries’ legal traditions and institutional quality.Paper three investigates why legal traditions matter for law development, institutions for creditors and investors, as well as the development of banking systems. The paper provides strong supports for the law and finance theory that legal traditions strongly matter for legal systems development in common law countries but provide partial support for the influence of institutions on bank systems development.The fourth paper investigates the role of ownership on bank efficiency. A novel approach is applied which addresses the incidental parameter problem associated with Stochastic Frontier Analysis (SFA). Results show both cost and profit efficiency’ superiority of foreign and privately-owned banks.
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| 19. |
- Schael, S, et al.
(författare)
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Precision electroweak measurements on the Z resonance
- 2006
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Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Forskningsöversikt (refereegranskat)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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| 20. |
- Schuette, Moritz, et al.
(författare)
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Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal carcinoma represents a heterogeneous entity, with only a fraction of the tumours responding to available therapies, requiring a better molecular understanding of the disease in precision oncology. To address this challenge, the OncoTrack consortium recruited 106 CRC patients (stages I-IV) and developed a pre-clinical platform generating a compendium of drug sensitivity data totalling 44,000 assays testing 16 clinical drugs on patient-derived in vivo and in vitro models. This large biobank of 106 tumours, 35 organoids and 59 xenografts, with extensive omics data comparing donor tumours and derived models provides a resource for advancing our understanding of CRC. Models recapitulate many of the genetic and transcriptomic features of the donors, but defined less complex molecular sub-groups because of the loss of human stroma. Linking molecular profiles with drug sensitivity patterns identifies novel biomarkers, including a signature outperforming RAS/RAF mutations in predicting sensitivity to the EGFR inhibitor cetuximab.
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| 21. |
- Volkert, Dorothee, et al.
(författare)
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ESPEN guideline on clinical nutrition and hydration in geriatrics
- 2019
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Ingår i: Clinical Nutrition. - : Elsevier BV. - 0261-5614 .- 1532-1983. ; 38:1, s. 10-47
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Tidskriftsartikel (refereegranskat)abstract
- Background: Malnutrition and dehydration are widespread in older people, and obesity is an increasing problem. In clinical practice, it is often unclear which strategies are suitable and effective in counteracting these key health threats.Aim: To provide evidence-based recommendations for clinical nutrition and hydration in older persons in order to prevent and/or treat malnutrition and dehydration. Further, to address whether weight-reducing interventions are appropriate for overweight or obese older persons.Methods: This guideline was developed according to the standard operating procedure for ESPEN guidelines and consensus papers. A systematic literature search for systematic reviews and primary studies was performed based on 33 clinical questions in PICO format. Existing evidence was graded according to the SIGN grading system. Recommendations were developed and agreed in a multistage consensus process.Results: We provide eighty-two evidence-based recommendations for nutritional care in older persons, covering four main topics: Basic questions and general principles, recommendations for older persons with malnutrition or at risk of malnutrition, recommendations for older patients with specific diseases, and recommendations to prevent, identify and treat dehydration. Overall, we recommend that all older persons shall routinely be screened for malnutrition in order to identify an existing risk early. Oral nutrition can be supported by nursing interventions, education, nutritional counseling, food modification and oral nutritional supplements. Enteral nutrition should be initiated if oral, and parenteral if enteral nutrition is insufficient or impossible and the general prognosis is altogether favorable. Dietary restrictions should generally be avoided, and weight-reducing diets shall only be considered in obese older persons with weight-related health problems and combined with physical exercise. All older persons should be considered to be at risk of low-intake dehydration and encouraged to consume adequate amounts of drinks. Generally, interventions shall be individualized, comprehensive and part of a multimodal and multidisciplinary team approach.Conclusion: A range of effective interventions is available to support adequate nutrition and hydration in older persons in order to maintain or improve nutritional status and improve clinical course and quality of life. These interventions should be implemented in clinical practice and routinely used.
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| 22. |
- Volkert, Dorothee, et al.
(författare)
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ESPEN practical guideline : Clinical nutrition and hydration in geriatrics
- 2022
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Ingår i: Clinical Nutrition. - : Elsevier. - 0261-5614 .- 1532-1983. ; 41:4, s. 958-989
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Tidskriftsartikel (refereegranskat)abstract
- Background: Malnutrition and dehydration are widespread in older people, and obesity is an increasing problem. In clinical practice, it is often unclear which strategies are suitable and effective in counter-acting these key health threats.Aim: To provide evidence-based recommendations for clinical nutrition and hydration in older persons in order to prevent and/or treat malnutrition and dehydration. Further, to address whether weight-reducing interventions are appropriate for overweight or obese older persons.Methods: This guideline was developed according to the standard operating procedure for ESPEN guidelines and consensus papers. A systematic literature search for systematic reviews and primary studies was performed based on 33 clinical questions in PICO format. Existing evidence was graded according to the SIGN grading system. Recommendations were developed and agreed in a multistage consensus process.Results: We provide eighty-two evidence-based recommendations for nutritional care in older persons, covering four main topics: Basic questions and general principles, recommendations for older persons with malnutrition or at risk of malnutrition, recommendations for older patients with specific diseases, and recommendations to prevent, identify and treat dehydration. Overall, we recommend that all older persons shall routinely be screened for malnutrition in order to identify an existing risk early. Oral nutrition can be supported by nursing interventions, education, nutritional counselling, food modifica-tion and oral nutritional supplements. Enteral nutrition should be initiated if oral, and parenteral if enteral nutrition is insufficient or impossible and the general prognosis is altogether favorable. Dietary restrictions should generally be avoided, and weight-reducing diets shall only be considered in obese older persons with weight-related health problems and combined with physical exercise. All older persons should be considered to be at risk of low-intake dehydration and encouraged to consume adequate amounts of drinks. Generally, interventions shall be individualized, comprehensive and part of a multimodal and multidisciplinary team approach.Conclusion: A range of effective interventions is available to support adequate nutrition and hydration in older persons in order to maintain or improve nutritional status and improve clinical course and quality of life. These interventions should be implemented in clinical practice and routinely used.
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| 23. |
- Wang, Yunzhang, et al.
(författare)
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Epigenetic influences on aging : a longitudinal genome-wide methylation study in old Swedish twins
- 2018
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Ingår i: Epigenetics. - : Informa UK Limited. - 1559-2294 .- 1559-2308. ; 13:9, s. 975-987
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Tidskriftsartikel (refereegranskat)abstract
- Age-related changes in DNA methylation were observed in cross-sectional studies, but longitudinal evidence is still limited. Here, we aimed to characterize longitudinal age-related methylation patterns using 1011 blood samples collected from 385 Swedish twins (age at entry: mean 69 and standard deviation 9.7, 73 monozygotic and 96 dizygotic pairs) up to five times (mean 2.6) over 20 years (mean 8.7). We identified 1316 age-associated methylation sites (P<1.3x10(-7)) using a longitudinal epigenome-wide association study design. We measured how estimated cellular compositions changed with age and how much they confounded the age effect. We validated the results in two independent longitudinal cohorts, where 118 CpGs were replicated in Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, 390 samples) (P<3.9x10(-5)), 594 in Lothian Birth Cohort (LBC, 3018 samples) (P<5.1x10(-5)) and 63 in both. Functional annotation of age-associated CpGs showed enrichment in CCCTC-binding factor (CTCF) and other transcription factor binding sites. We further investigated genetic influences on methylation and found no interaction between age and genetic effects in the 1316 age-associated CpGs. Moreover, in the same CpGs, methylation differences within twin pairs increased with 6.4% over 10 years, where monozygotic twins had smaller intra-pair differences than dizygotic twins. In conclusion, we show that age-related methylation changes persist in a longitudinal perspective, and are fairly stable across cohorts. The changes are under genetic influence, although this effect is independent of age. Moreover, methylation variability increase over time, especially in age-associated CpGs, indicating the increase of environmental contributions on DNA methylation with age.
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| 24. |
- Waschitz, Y., et al.
(författare)
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Independent isotopic fission yields of Cf-252 spontaneous fission via mass measurements at the FRS Ion Catcher
- 2023
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Ingår i: 15th International Conference on Nuclear Data for Science and Technology, ND2022. - : EDP Sciences.
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Konferensbidrag (refereegranskat)abstract
- We present first preliminary results of a novel method for measuring independent isotopic fission yields (IIFYs) of spontaneous fission (SF) via direct mass measurements, at the FRS Ion Catcher (FRS -IC) at GSI. Fission products were generated from a Cf-252 source installed in a cryogenic stopping cell, and were identified and counted with the multiple-reflection time-of-flight mass spectrometer (MR-TOR-MS) of the FRS-IC, utilizing well-established measurement and data analysis methods. The MR-TOR-MS resolves isobars unambiguously, even with limited statistics, and its non-scanning nature ensures minimal relative systematic uncertainties amongst fission products. The analysis for extracting IIFYs includes isotope-dependent efficiency corrections for all components of the FRS -IC. In particular, we applied a self-consistent technique that takes into account the element-dependent survival efficiencies in the CSC, due to chemical reactions with the buffer gas. Our IIFY results, which cover several tens of fission products in the less -accessible high-mass peak (Z = 56 to 63) down to fission yields at the level of 10(-5), are generally similar to those of the nuclear database ENDF/B-VII.O. Nevertheless, they reveal some structures that are not observed in the database smooth trends. These are the first results of a planned campaign to investigate IIFY distributions of spontaneous fission at the FRS-IC. Upcoming experiments will extend our results to wider Z and N ranges, lower fission yields, and other spontaneously-fissioning actinides.
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