| 1. |
- Mancina, Rosellina Margherita, et al.
(författare)
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A two gene-based risk score predicts alcoholic cirrhosis development in males with at-risk alcohol consumption
- 2019
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Ingår i: Application of Clinical Genetics. - 1178-704X. ; 12, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alcoholic cirrhosis represents 1% of all cause-of-deaths worldwide. Its incidence is higher in males and results from the combination of environmental and genetic factors. Among all the genetic determinants of alcoholic cirrhosis, the patatin-like phospholipase domain protein 3 (PNPLA3) rs738409 represents the most widely validated determinant. Recent cross-sectional studies on alcohol abusers identified transmembrane-6 superfamily member 2 (TM6SF2) rs58542926, membrane bound O-acyltransferase domain containing 7 (MBOAT7) rs641738, and cluster of differentiation 14 (CD14) rs2569190 as new genetic risk factors for alcoholic cirrhosis. We aimed to develop a gene-based risk score to predict the incidence of alcoholic cirrhosis in males with at-risk alcohol consumption. Materials and methods: A total of 416 male at-risk alcohol drinkers were retrospectively examined. The association between alcoholic cirrhosis incidence and PNPLA3, CD14, TM6SF2, and MBOAT7 variants was tested. Age at onset of at-risk alcohol consumption, age, and body mass index (BMI) were included as covariates to determine the prediction score for alcoholic cirrhosis incidence by evaluating time-dependent receiver operating characteristic curves. Results: We found that PNPLA3, CD14, and TM6SF2 were associated with alcoholic cirrhosis prevalence. PNPLA3 and CD14 were also associated with its incidence. The best predictive score formula was (age at onset of at-risk alcohol consumption x 0.1) + (number of CD14 allele T) + (number of PNPLA3 allele M) + (BMI x 0.1). A threshold of 7.27 was identified as cutoff for the predictive risk of alcoholic cirrhosis development in 36 years from the onset of at-risk alcohol consumption with 70.1% sensitivity and 78.7% specificity. Conclusion: We developed the first score for alcoholic cirrhosis prediction that combines clinical and genetic factors.
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| 2. |
- Burza, Maria Antonella, 1980, et al.
(författare)
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PNPLA3 I148M (rs738409) genetic variant and age at onset of at-risk alcohol consumption are independent risk factors for alcoholic cirrhosis
- 2014
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Ingår i: Liver International. - : Wiley. - 1478-3223 .- 1478-3231. ; 34:4, s. 514-520
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims Environmental and genetic factors contribute to alcoholic cirrhosis onset. In particular, age at exposure to liver stressors has been shown to be important in progression to fibrosis in hepatitis C individuals. However, no definite data on the role of age at onset of at-risk alcohol consumption are available. Moreover, patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M (rs738409) variant has been associated with alcoholic cirrhosis, but only in cross-sectional studies. The aim of this study was to investigate the role of age at onset of at-risk alcohol consumption and PNPLA3 I148M variant on alcoholic cirrhosis incidence. A total of 384 at-risk alcohol drinkers were retrospectively examined. The association among age at onset of at-risk alcohol consumption, PNPLA3 I148M variant and cirrhosis incidence was tested. A higher incidence of alcoholic cirrhosis was observed in individuals with an older (>= 24years) compared with a younger (<24) age at onset of at-risk alcohol consumption (P-value<0.001). Moreover, PNPLA3 148M allele carriers showed an increased incidence of cirrhosis (P-value<0.001). Both age at onset of at-risk alcohol consumption and PNPLA3148M allele were independent risk factors for developing cirrhosis (H.R. (95% C.I.): 2.76 (2.18-3.50), P-value<0.001; 1.53(1.07-2.19), P-value=0.021 respectively). The 148M allele was associated with a two-fold increased risk of cirrhosis in individuals with a younger compared with an older age at onset of at-risk alcohol consumption (H.R. (95% C.I.): 3.03(1.53-6.00) vs. 1.61(1.09-2.38). Age at onset of at-risk alcohol consumption and PNPLA3 I148M genetic variant are independently associated with alcoholic cirrhosis incidence.
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| 3. |
- Palmer, C. N. A., et al.
(författare)
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Paradoxical Lower Serum Triglyceride Levels and Higher Type 2 Diabetes Mellitus Susceptibility in Obese Individuals with the PNPLA3 148M Variant
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Obesity is highly associated with elevated serum triglycerides, hepatic steatosis and type 2 diabetes (T2D). The I148M (rs738409) genetic variant of patatin-like phospholipase domain-containing 3 gene (PNPLA3) is known to modulate hepatic triglyceride accumulation, leading to steatosis. No association between PNPLA3 I148M genotype and T2D in Europeans has been reported. Aim of this study is to examine the relationship between PNPLA3 I148M genotypes and serum triglycerides, insulin resistance and T2D susceptibility by testing a gene-environment interaction model with severe obesity. Methods and Findings: PNPLA3 I148M was genotyped in a large obese cohort, the SOS study (n = 3,473) and in the Go-DARTS (n = 15,448), a T2D case-control study. Metabolic parameters were examined across the PNPLA3 I148M genotypes in participants of the SOS study at baseline and at 2- and 10-year follow up after bariatric surgery or conventional therapy. The associations with metabolic parameters were validated in the Go-DARTS study. Serum triglycerides were found to be lower in the PNPLA3 148M carriers from the SOS study at baseline and from the Go-DARTS T2D cohort. An increased risk for T2D conferred by the 148M allele was found in the SOS study (O.R. 1.09, 95% C.I. 1.01-1.39, P = 0.040) and in severely obese individuals in the Go-DARTS study (O. R. 1.37, 95% C.I. 1.13-1.66, P = 0.001). The 148M allele was no longer associated with insulin resistance or T2D after bariatric surgery in the SOS study and no association with the 148M allele was observed in the less obese (BMI<35) individuals in the Go-DARTS study (P for interaction = 0.002). This provides evidence for the obesity interaction with 148M allele and T2D risk in a large-scale cross-sectional and a prospective interventional study. Conclusions: Severely obese individuals carrying the PNPLA3 148M allele have lower serum triglyceride levels, are more insulin resistant and more susceptible to T2D. This study supports the hypothesis that obesity-driven hepatic lipid accumulation may contribute to T2D susceptibility.
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| 4. |
- Coury, M., et al.
(författare)
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Injection and transport properties of fast electrons in ultraintense laser-solid interactions
- 2013
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Ingår i: Physics of Plasmas. - : AIP Publishing. - 1070-664X .- 1089-7674. ; 20:4
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Tidskriftsartikel (refereegranskat)abstract
- Fast electron injection and transport in solid foils irradiated by sub-picosecond-duration laser pulses with peak intensity equal to 4 x 10(20)W/cm(2) is investigated experimentally and via 3D simulations. The simulations are performed using a hybrid-particle-in-cell (PIC) code for a range of fast electron beam injection conditions, with and without inclusion of self-generated resistive magnetic fields. The resulting fast electron beam transport properties are used in rear-surface plasma expansion calculations to compare with measurements of proton acceleration, as a function of target thickness. An injection half-angle of similar to 50 degrees - 70 degrees is inferred, which is significantly larger than that derived from previous experiments under similar conditions. (C) 2013 American Institute of Physics. [http://dx.doi.org/10.1063/1.4799726]
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| 5. |
- McKenna, P., et al.
(författare)
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Effect of Lattice Structure on Energetic Electron Transport in Solids Irradiated by Ultraintense Laser Pulses
- 2011
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Ingår i: Physical Review Letters. - 1079-7114. ; 106:18
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Tidskriftsartikel (refereegranskat)abstract
- The effect of lattice structure on the transport of energetic (MeV) electrons in solids irradiated by ultraintense laser pulses is investigated using various allotropes of carbon. We observe smooth electron transport in diamond, whereas beam filamentation is observed with less ordered forms of carbon. The highly ordered lattice structure of diamond is shown to result in a transient state of warm dense carbon with metalliclike conductivity, at temperatures of the order of 1-100 eV, leading to suppression of electron beam filamentation.
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| 6. |
- Coury, M., et al.
(författare)
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Influence of laser irradiated spot size on energetic electron injection and proton acceleration in foil targets
- 2012
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 100:7
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Tidskriftsartikel (refereegranskat)abstract
- The influence of irradiated spot size on laser energy coupling to electrons, and subsequently to protons, in the interaction of intense laser pulses with foil targets is investigated experimentally. Proton acceleration is characterized for laser intensities ranging from 2 x 10(18) - 6 x 10(20) W/cm(2), by (1) variation of the laser energy for a fixed irradiated spot size, and (2) by variation of the spot size for a fixed energy. At a given laser pulse intensity, the maximum proton energy is higher under defocus illumination compared to tight focus and the results are explained in terms of geometrical changes to the hot electron injection. (C) 2012 American Institute of Physics. [doi:10.1063/1.3685615]
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| 7. |
- Yuan, X. H., et al.
(författare)
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Effects of target pre-heating and expansion on terahertz radiation production from intense laser-solid interactions
- 2014
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Ingår i: High Power Laser Science and Engineering. - : Cambridge University Press (CUP). - 2095-4719 .- 2052-3289. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- The first experimental measurements of intense laser-driven terahertz (THz) radiation from a solid target which is preheated by an intense pulse of laser-accelerated protons is reported. The total energy of the THz radiation is found to decrease by approximately a factor of 2 compared to a cold target reference. This is attributed to an increase in the scale length of the preformed plasma, driven by proton heating, at the front surface of the target, where the THz radiation is generated. The results show the importance of controlling the preplasma scale length for THz production.
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| 8. |
- Burza, Maria Antonella, 1980, et al.
(författare)
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Long-Term Effect of Bariatric Surgery on Liver Enzymes in the Swedish Obese Subjects (SOS) Study
- 2013
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:3
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aim: Obesity is associated with elevated serum transaminase levels and non- Methods: The Swedish Obese Subjects (SOS) study is a prospective controlled intervention study Results: Compared to usual care, bariatric surgery was associated with lower serum ALT and AST levels Conclusions: Bariatric surgery results in a sustained reduction in transaminase levels and a long-term
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| 9. |
- Gopal, A., et al.
(författare)
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MegaGauss magnetic field generation by ultra-short pulses at relativistic intensities
- 2013
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Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 0741-3335 .- 1361-6587. ; 55:3
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Tidskriftsartikel (refereegranskat)abstract
- We report the experimental studies on megaGauss magnetic field generation using a 35 femtosecond laser at relativistic intensities. The polarization change of the self-generated harmonics was recorded to estimate the magnetic field. A parameter scan was performed by varying the input laser intensity as well as the contrast ratio. External optical probing diagnostics were performed using the second harmonic of the incident laser. Additionally, the optical transition radiation from the rear of the target was also recorded.
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| 10. |
- MacLellan, D. A., et al.
(författare)
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Annular Fast Electron Transport in Silicon Arising from Low-Temperature Resistivity
- 2013
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Ingår i: Physical Review Letters. - 1079-7114. ; 111:9
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Tidskriftsartikel (refereegranskat)abstract
- Fast electron transport in Si, driven by ultraintense laser pulses, is investigated experimentally and via 3D hybrid particle-in-cell simulations. A transition from a Gaussian-like to an annular fast electron beam profile is demonstrated and explained by resistively generated magnetic fields. The results highlight the potential to completely transform the beam transport pattern by tailoring the resistivity-temperature profile at temperatures as low as a few eV.
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