| 1. |
- Walker, Anthony P, et al.
(author)
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Horizon 2020 EuPRAXIA design study
- 2017
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In: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 874:1
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Journal article (peer-reviewed)abstract
- The Horizon 2020 Project EuPRAXIA ("European Plasma Research Accelerator with eXcellence In Applications") is preparing a conceptual design report of a highly compact and cost-effective European facility with multi-GeV electron beams using plasma as the acceleration medium. The accelerator facility will be based on a laser and/or a beam driven plasma acceleration approach and will be used for photon science, high-energy physics (HEP) detector tests, and other applications such as compact X-ray sources for medical imaging or material processing. EuPRAXIA started in November 2015 and will deliver the design report in October 2019. EuPRAXIA aims to be included on the ESFRI roadmap in 2020.
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| 2. |
- Clifford, B. L., et al.
(author)
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FXR activation protects against NAFLD via bile-acid-dependent reductions in lipid absorption
- 2021
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In: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 33:8
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Journal article (peer-reviewed)abstract
- FXR agonists are used to treat non-alcoholic fatty liver disease (NAFLD), in part because they reduce hepatic lipids. Here, we show that FXR activation with the FXR agonist GSK2324 controls hepatic lipids via reduced absorption and selective decreases in fatty acid synthesis. Using comprehensive lipidomic analyses, we show that FXR activation in mice or humans specifically reduces hepatic levels of mono-and polyunsaturated fatty acids (MUFA and PUFA). Decreases in MUFA are due to FXR-dependent repression of Scd1, Dgat2, and Lpin1 expression, which is independent of SHP and SREBP1c. FXR-dependent decreases in PUFAs are mediated by decreases in lipid absorption. Replenishing bile acids in the diet prevented decreased lipid absorption in GSK2324-treated mice, suggesting that FXR reduces absorption via decreased bile acids. We used tissue-specific FXR KO mice to show that hepatic FXR controls lipogenic genes, whereas intestinal FXR controls lipid absorption. Together, our studies establish two distinct pathways by which FXR regulates hepatic lipids.
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| 3. |
- Mörtzell Henriksson, Monica, et al.
(author)
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Adverse events in apheresis : an update of the WAA registry data
- 2016
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In: Transfusion and apheresis science. - : Elsevier. - 1473-0502 .- 1878-1683. ; 54:1, s. 2-15
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Research review (peer-reviewed)abstract
- Apheresis with different procedures and devices are used for a variety of indications that may have different adverse events (AEs). The aim of this study was to clarify the extent and possible reasons of various side effects based on data from a multinational registry. The WAA-apheresis registry data focus on adverse events in a total of 50846 procedures in 7142 patients (42% women). AEs were graded as mild, moderate (need for medication), severe (interruption due to the AE) or death (due to AE). More AEs occurred during the first procedures versus subsequent (8.4 and 5.5%, respectively). AEs were mild in 2.4% (due to access 54%, device 7%, hypotension 15%, tingling 8%), moderate in 3% (tingling 58%, urticaria 15%, hypotension 10%, nausea 3%), and severe in 0.4% of procedures (syncope/hypotension 32%, urticaria 17%, chills/fever 8%, arrhythmia/asystole 4.5%, nausea/vomiting 4%). Hypotension was most common if albumin was used as the replacement fluid, and urticaria when plasma was used. Arrhythmia occurred to similar extents when using plasma or albumin as replacement. In 64% of procedures with bronchospasm, plasma was part of the replacement fluid used. Severe AEs are rare. Although most reactions are mild and moderate, several side effects may be critical for the patient. We present side effects in relation to the procedures and suggest that safety is increased by regular vital sign measurements, cardiac monitoring and by having emergency equipment nearby.
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| 4. |
- Ovadia, C., et al.
(author)
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Ursodeoxycholic acid enriches intestinal bile salt hydrolase-expressing Bacteroidetes in cholestatic pregnancy
- 2020
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- Ursodeoxycholic acid (UDCA) treatment can reduce itch and lower endogenous serum bile acids in intrahepatic cholestasis of pregnancy (ICP). We sought to determine how it could influence the gut environment in ICP to alter enterohepatic signalling. The gut microbiota and bile acid content were determined in faeces from 35 pregnant women (14 with uncomplicated pregnancies and 21 with ICP, 17 receiving UDCA). Faecal bile salt hydrolase activity was measured using a precipitation assay. Serum fibroblast growth factor 19 (FGF19) and 7α-hydroxy-4-cholesten-3-one (C4) concentrations were measured following a standardised diet for 21 hours. Women with a high ratio of Bacteroidetes to Firmicutes were more likely to be treated with UDCA (Fisher’s exact test p = 0.0178) than those with a lower ratio. Bile salt hydrolase activity was reduced in women with low Bacteroidetes:Firmicutes. Women taking UDCA had higher faecal lithocholic acid (p < 0.0001), with more unconjugated bile acids than women with untreated ICP or uncomplicated pregnancy. UDCA-treatment increased serum FGF19, and reduced C4 (reflecting lower bile acid synthesis). During ICP, UDCA treatment can be associated with enrichment of the gut microbiota with Bacteroidetes. These demonstrate high bile salt hydrolase activity, which deconjugates bile acids enabling secondary modification to FXR agonists, enhancing enterohepatic feedback via FGF19. © 2020, The Author(s).
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| 5. |
- Pirozhkov, A. S., et al.
(author)
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Diagnostic of laser contrast using target reflectivity
- 2009
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In: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 94:24
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Journal article (peer-reviewed)abstract
- Using three different laser systems, we demonstrate a convenient and simple plasma based diagnostic of the contrast of high-power short-pulse lasers. The technique is based on measuring the specular reflectivity from a solid target. The reflectivity remains high even at relativistic intensities above 10(19) W/cm(2) in the case of a high-contrast prepulse-free laser. On the contrary, the specular reflectivity drops with increasing intensities in the case of systems with insufficient contrast due to beam breakup and increased absorption caused by preplasma.
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| 6. |
- Giuffrida, L., et al.
(author)
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Nano and micro structured targets to modulate the spatial profile of laser driven proton beams
- 2017
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In: Journal of Instrumentation. - 1748-0221. ; 12:3, s. article no C03040 -
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Journal article (peer-reviewed)abstract
- Nano and micro structured thin (μ m-scale) foils were designed, fabricated and irradiated with the high intensity laser system operating at LLC (Lund Laser Centre, Sweden) in order to systematically study and improve the main proton beam parameters. Nano-spheres deposited on the front (laser irradiated) surface of a flat Mylar foil enabled a small enhancement of the maximum energy and number of the accelerated protons. Nano-spheres on the rear side allowed to modify the proton beam spatial profile. In particular, with nanospheres deposited on the rear of the target, the proton beam spatial homogeneity was clearly enhanced. Silicon nitride thin foils having micro grating structures (with different step dimensions) on the rear surface were also used as targets to influence the divergence of the proton beam and drastically change its shape through a sort of stretching effect. The target fabrication process used for the different target types is described, and representative experimental results are shown and discussed along with supporting 3D particle-in-cell simulations. © 2017 IOP Publishing Ltd and Sissa Medialab srl.
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| 7. |
- Schneider, K. M., et al.
(author)
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Gut microbiota depletion exacerbates cholestatic liver injury via loss of FXR signalling
- 2021
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In: Nature Metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 3:9, s. 1228-1241
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Journal article (peer-reviewed)abstract
- Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown aetiology for which there are no approved therapeutic options. Patients with PSC display changes in gut microbiota and in bile acid (BA) composition; however, the contribution of these alterations to disease pathogenesis remains controversial. Here we identify a role for microbiota-dependent changes in BA synthesis that modulates PSC pathophysiology. In a genetic mouse model of PSC, we show that loss of microbiota-mediated negative feedback control of BA synthesis results in increased hepatic BA concentrations, disruption of bile duct barrier function and, consequently, fatal liver injury. We further show that these changes are dependent on decreased BA signalling to the farnesoid X receptor, which modulates the activity of the rate-limiting enzyme in BA synthesis, CYP7A1. Moreover, patients with advanced stages of PSC show suppressed BA synthesis as measured by serum C4 levels, which is associated with poor disease prognosis. Our preclinical data highlight the microbiota-dependent dynamics of BA metabolism in cholestatic liver disease, which could be important for future therapies targeting BA and gut microbiome interactions, and identify C4 as a potential biomarker to functionally stratify patients with PSC and predict disease outcomes. Patients with primary sclerosing cholangitis (PSC), a chronic cholestatic liver disease, display changes in the gut microbiota and in bile acid composition. Schneider, Candels and colleagues identify a role for microbiota-dependent regulation of bile acid synthesis through farnesoid X receptor signalling, which is relevant for PSC disease progression.
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| 8. |
- Shirazi, M., et al.
(author)
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Effects on readiness to change of an educational intervention on depressive disorders for general physicians in primary care based on a modified Prochaska model : a randomized controlled study
- 2008
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In: Family Practice. - : Oxford University Press (OUP). - 0263-2136 .- 1460-2229. ; 25:2, s. 98-104
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Journal article (peer-reviewed)abstract
- Background: The Prochaska model of readiness to change has been proposed to be used in educational interventions to improve medical care. Objective: To evaluate the impact on readiness to change of an educational intervention on management of depressive disorders based on a modified version of the Prochaska model in comparison with a standard programme of continuing medical education (CME). Methods: This is a randomized controlled trial within primary care practices in southern Tehran, Iran. The participants included 192 general physicians working in primary care (GPs) were recruited after random selection and randomized to intervention (96) and control (96). Intervention consisted of interactive, learner-centred educational methods in large and small group settings depending on the GPs' stages of readiness to change. Change in stage of readiness to change measured by the modified version of the Prochaska questionnaire was the main outcome measure. Results The final number of participants was 78 (81%) in the intervention arm and 81 (84%) in the control arm. Significantly (P < 0.01), more GPs (57/96 = 59% versus 12/96 = 12%) in the intervention group changed to higher stages of readiness to change. The intervention effect was 46% points (P < 0.001) and 50% points (P < 0.001) in the large and small group setting, respectively. Conclusions: Educational formats that suit different stages of learning can support primary care doctors to reach higher stages of behavioural change in the topic of depressive disorders. Our findings have practical implications for conducting CME programmes in Iran and are possibly also applicable in other parts of the world.
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| 9. |
- Elliott, James A., et al.
(author)
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Diabetes Self-Management and Education of People Living with Diabetes : A Survey in Primary Health Care in Muscat Oman
- 2013
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:2, s. e57400-
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Journal article (peer-reviewed)abstract
- Background: Although the prevalence of type 2 diabetes in Oman is high and rising, information on how people were self-managing their disease has been lacking. The objective of this study was therefore to assess diabetes self-management and education (DSME) among people living with type 2 diabetes in Oman. Methods: A questionnaire survey was conducted in public primary health care centres in Muscat. Diabetes self-management and education was assessed by asking how patients recognized and responded to hypo- and hyperglycaemia, and if they had developed strategies to maintain stable blood glucose levels. Patients' demographic information, self-treatment behaviours, awareness of potential long-term complications, and attitudes concerning diabetes management were also recorded. Associations between these factors and diabetes self-management and education were analysed. Results: In total, 309 patients were surveyed. A quarter (26%, n = 83) were unaware how to recognize hypoglycaemia or respond to it (26%, n = 81). Around half (49%, n = 151), could not recognize hyperglycaemia and more than half could not respond to it (60%, n = 184). Twelve percent (n = 37) of the patients did not have any strategies to stabilize their blood glucose levels. Patients with formal education generally had more diabetes self-management and education than those without (p<0.001), as had patients with longer durations of diabetes (p<0.01). Self-monitoring of blood glucose was practiced by 38% (n = 117) of the patients, and insulin was used by 22% (n = 67), of which about one third independently adjusted dosages. Patients were most often aware of complications concerning loss of vision, renal failure and cardiac problems. Many patients desired further health education. Conclusions: Many patients displayed dangerous diabetes self-management and education knowledge gaps. The findings suggest a need for improving knowledge transfer to people living with diabetes in the Omani clinical setting.
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| 10. |
- Giuffrida, L., et al.
(author)
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Manipulation of laser-accelerated proton beam profiles by nanostructured and microstructured targets
- 2017
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In: Physical Review Accelerators and Beams. - 2469-9888. ; 20:8, s. 081301-
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Journal article (peer-reviewed)abstract
- Nanostructured and microstructured thin foils have been fabricated and used experimentally as targets to manipulate the spatial profile of proton bunches accelerated through the interaction with high intensity laser pulses (6 x 1019 W/cm(2)). Monolayers of polystyrene nanospheres were placed on the rear surfaces of thin plastic targets to improve the spatial homogeneity of the accelerated proton beams. Moreover, thin targets with grating structures of various configurations on their rear sides were used tomodify the proton beam divergence. Experimental results are presented, discussed, and supported by 3D particle-in-cell numerical simulations.
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