| 1. |
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| 2. |
- Feroci, M., et al.
(författare)
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The large observatory for x-ray timing
- 2014
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 9780819496126
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Konferensbidrag (refereegranskat)abstract
- The Large Observatory For x-ray Timing (LOFT) was studied within ESA M3 Cosmic Vision framework and participated in the final downselection for a launch slot in 2022-2024. Thanks to the unprecedented combination of effective area and spectral resolution of its main instrument, LOFT will study the behaviour of matter under extreme conditions, such as the strong gravitational field in the innermost regions of accretion flows close to black holes and neutron stars, and the supranuclear densities in the interior of neutron stars. The science payload is based on a Large Area Detector (LAD, 10 m2 effective area, 2-30 keV, 240 eV spectral resolution, 1° collimated field of view) and a Wide Field Monitor (WFM, 2-50 keV, 4 steradian field of view, 1 arcmin source location accuracy, 300 eV spectral resolution). The WFM is equipped with an on-board system for bright events (e.g. GRB) localization. The trigger time and position of these events are broadcast to the ground within 30 s from discovery. In this paper we present the status of the mission at the end of its Phase A study.
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| 3. |
- Feroci, M., et al.
(författare)
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LOFT - The large observatory for x-ray timing
- 2012
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE - International Society for Optical Engineering. - 9780819491442 ; , s. 84432D-
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Konferensbidrag (refereegranskat)abstract
- The LOFT mission concept is one of four candidates selected by ESA for the M3 launch opportunity as Medium Size missions of the Cosmic Vision programme. The launch window is currently planned for between 2022 and 2024. LOFT is designed to exploit the diagnostics of rapid X-ray flux and spectral variability that directly probe the motion of matter down to distances very close to black holes and neutron stars, as well as the physical state of ultradense matter. These primary science goals will be addressed by a payload composed of a Large Area Detector (LAD) and a Wide Field Monitor (WFM). The LAD is a collimated (<1 degree field of view) experiment operating in the energy range 2-50 keV, with a 10 m2 peak effective area and an energy resolution of 260 eV at 6 keV. The WFM will operate in the same energy range as the LAD, enabling simultaneous monitoring of a few-steradian wide field of view, with an angular resolution of <5 arcmin. The LAD and WFM experiments will allow us to investigate variability from submillisecond QPO's to yearlong transient outbursts. In this paper we report the current status of the project.
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| 4. |
- Bar, N., et al.
(författare)
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A reference map of potential determinants for the human serum metabolome
- 2020
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Ingår i: Nature. - : Nature Research. - 0028-0836 .- 1476-4687. ; 588:7836, s. 135-140
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Tidskriftsartikel (refereegranskat)abstract
- The serum metabolome contains a plethora of biomarkers and causative agents of various diseases, some of which are endogenously produced and some that have been taken up from the environment1. The origins of specific compounds are known, including metabolites that are highly heritable2,3, or those that are influenced by the gut microbiome4, by lifestyle choices such as smoking5, or by diet6. However, the key determinants of most metabolites are still poorly understood. Here we measured the levels of 1,251 metabolites in serum samples from a unique and deeply phenotyped healthy human cohort of 491 individuals. We applied machine-learning algorithms to predict metabolite levels in held-out individuals on the basis of host genetics, gut microbiome, clinical parameters, diet, lifestyle and anthropometric measurements, and obtained statistically significant predictions for more than 76% of the profiled metabolites. Diet and microbiome had the strongest predictive power, and each explained hundreds of metabolites—in some cases, explaining more than 50% of the observed variance. We further validated microbiome-related predictions by showing a high replication rate in two geographically independent cohorts7,8 that were not available to us when we trained the algorithms. We used feature attribution analysis9 to reveal specific dietary and bacterial interactions. We further demonstrate that some of these interactions might be causal, as some metabolites that we predicted to be positively associated with bread were found to increase after a randomized clinical trial of bread intervention. Overall, our results reveal potential determinants of more than 800 metabolites, paving the way towards a mechanistic understanding of alterations in metabolites under different conditions and to designing interventions for manipulating the levels of circulating metabolites.
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| 5. |
- Wilman, H. R., et al.
(författare)
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Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration
- 2019
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Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 71:3, s. 594-602
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Excess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases. Methods: First, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n = 1,513 from IMI DIRECT). Second, we used Mendelian randomisation to test the causal effects of 25 predominantly metabolic traits on liver iron content. Third, we tested phenome-wide associations between liver iron variants and 770 traits and disease outcomes. Results: We identified 3 independent genetic variants (rs1800562 [C282Y] and rs1799945 [H63D] in HFE and rs855791 [V736A] in TMPRSS6) associated with liver iron content that reached the GWAS significance threshold (p <5 × 10−8). The 2 HFE variants account for ∼85% of all cases of hereditary haemochromatosis. Mendelian randomisation analysis provided evidence that higher central obesity plays a causal role in increased liver iron content. Phenome-wide association analysis demonstrated shared aetiopathogenic mechanisms for elevated liver iron, high blood pressure, cirrhosis, malignancies, neuropsychiatric and rheumatological conditions, while also highlighting inverse associations with anaemias, lipidaemias and ischaemic heart disease. Conclusion: Our study provides genetic evidence that mechanisms underlying higher liver iron content are likely systemic rather than organ specific, that higher central obesity is causally associated with higher liver iron, and that liver iron shares common aetiology with multiple metabolic and non-metabolic diseases. Lay summary: Excess liver iron content is common and is associated with liver diseases and metabolic diseases including diabetes, high blood pressure, and heart disease. We identified 3 genetic variants that are linked to an increased risk of developing higher liver iron content. We show that the same genetic variants are linked to higher risk of many diseases, but they may also be associated with some health advantages. Finally, we use genetic variants associated with waist-to-hip ratio as a tool to show that central obesity is causally associated with increased liver iron content.
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| 6. |
- Altstadt, S.G., et al.
(författare)
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B-13,B-14(n,gamma) via Coulomb Dissociation for Nucleosynthesis towards the r-Process
- 2014
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Ingår i: Nuclear Data Sheets. - : Elsevier BV. - 1095-9904 .- 0090-3752. ; 120, s. 197-200
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Konferensbidrag (refereegranskat)abstract
- Radioactive beams of 14,15B produced by fragmentation of a primary 40Ar beam were directed onto a Pb target to investigate the neutron breakup within the Coulomb field. The experiment was performed at the LAND/R3B setup. Preliminary results for the Coulomb dissociation cross sections as well as for the astrophysically interesting inverse reactions, 13,14B(n,γ), are presented.
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| 7. |
- Aprile, E., et al.
(författare)
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First Results on the Scalar WIMP-Pion Coupling, Using the XENON1T Experiment
- 2019
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 122:7
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Tidskriftsartikel (refereegranskat)abstract
- We present first results on the scalar coupling of weakly interacting massive particles (WIMPs) to pions from 1 t yr of exposure with the XENON1T experiment. This interaction is generated when the WIMP couples to a virtual pion exchanged between the nucleons in a nucleus. In contrast to most nonrelativistic operators, these pion-exchange currents can be coherently enhanced by the total number of nucleons and therefore may dominate in scenarios where spin-independent WIMP-nucleon interactions are suppressed. Moreover, for natural values of the couplings, they dominate over the spin-dependent channel due to their coherence in the nucleus. Using the signal model of this new WIMP-pion channel, no significant excess is found, leading to an upper limit cross section of 6.4 x 10(-46) cm(2) (90% confidence level) at 30 GeV/c(2) WIMP mass.
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| 8. |
- Caesar, C., et al.
(författare)
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Beyond the neutron drip line: The unbound oxygen isotopes O-25 and O-26
- 2013
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Ingår i: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993 .- 0556-2813. ; 88:3
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Tidskriftsartikel (refereegranskat)abstract
- The very neutron-rich oxygen isotopes O-25 and O-26 are investigated experimentally and theoretically. The unbound states are populated in an experiment performed at the R3B-LAND setup at GSI via proton-knockout reactions from F-26 and F-27 at relativistic energies around 442 and 414 MeV/nucleon, respectively. From the kinematically complete measurement of the decay into O-24 plus one or two neutrons, the O-25 ground-state energy and width are determined, and upper limits for the O-26 ground-state energy and lifetime are extracted. In addition, the results provide indications for an excited state in O-26 at around 4 MeV. The experimental findings are compared to theoretical shell-model calculations based on chiral two- and three-nucleon (3N) forces, including for the first time residual 3N forces, which are shown to be amplified as valence neutrons are added.
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| 9. |
- Vandebrouck, M., et al.
(författare)
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Effective proton-neutron interaction near the drip line from unbound states in F-25,F-26
- 2017
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Ingår i: Physical Review C. - 2469-9985 .- 2469-9993. ; 96:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Odd-odd nuclei, around doubly closed shells, have been extensively used to study proton-neutron interactions. However, the evolution of these interactions as a function of the binding energy, ultimately when nuclei become unbound, is poorly known. The F-26 nucleus, composed of a deeply bound pi 0d(5/2) proton and an unbound v0d(3/2) neutron on top of an O-24 core, is particularly adapted for this purpose. The coupling of this proton and neutron results in a J(pi) = 1(1)(+) - 4(1)(+) multiplet, whose energies must be determined to study the influence of the proximity of the continuum on the corresponding proton-neutron interaction. The J(pi) = 1(1)(+), 2(1)(+), 4(1)(+) bound states have been determined, and only a clear identification of the J(pi) = 3(1)(+) is missing. Purpose: We wish to complete the study of the J(pi) = 1(1)(+) - 4(1)(+) multiplet in F-26, by studying the energy and width of the J(pi) = 3(1)(+) unbound state. The method was first validated by the study of unbound states in F-25, for which resonances were already observed in a previous experiment. Method: Radioactive beams of Ne-26 and Ne-27, produced at about 440AMeV by the fragment separator at the GSI facility were used to populate unbound states in F-25 and F-26 via one-proton knockout reactions on a CH2 target, located at the object focal point of the (RB)-B-3/LAND setup. The detection of emitted. rays and neutrons, added to the reconstruction of the momentum vector of the A - 1 nuclei, allowed the determination of the energy of three unbound states in F-25 and two in F-26. Results: Based on its width and decay properties, the first unbound state in F-25, at the relative energy of 49(9) keV, is proposed to be a J(pi) = 1/ 2(-) arising from a p1/2 proton- hole state. In F-26, the first resonance at 323(33) keV is proposed to be the J(pi) = 3(1)(+) member of the J(pi) = 1(1)(+) - 4(1)(+) multiplet. Energies of observed states in F-25,F-26 have been compared to calculations using the independent-particle shell model, a phenomenological shell model, and the ab initio valence-space in-medium similarity renormalization group method. Conclusions: The deduced effective proton- neutron interaction is weakened by about 30-40% in comparison to the models, pointing to the need for implementing the role of the continuum in theoretical descriptions or to a wrong determination of the atomic mass of F-26.
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| 10. |
- Ciemala, M., et al.
(författare)
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Testing ab initio nuclear structure in neutron-rich nuclei : Lifetime measurements of second 2(+) state in C-16 and O-20
- 2020
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Ingår i: Physical Review C. - : AMER PHYSICAL SOC. - 2469-9985 .- 2469-9993. ; 101:2
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Tidskriftsartikel (refereegranskat)abstract
- To test the predictive power of ab initio nuclear structure theory, the lifetime of the second 2(+) state in neutron-rich O-20, tau(2(2)(+)) = 150(-30)(+80) fs, and an estimate for the lifetime of the second 2(+) state in C-16 have been obtained for the first time. The results were achieved via a novel Monte Carlo technique that allowed us to measure nuclear state lifetimes in the tens-to-hundreds of femtoseconds range by analyzing the Doppler-shifted gamma-transition line shapes of products of low-energy transfer and deep-inelastic processes in the reaction O-18 (7.0 MeV/u) + Ta-181. The requested sensitivity could only be reached owing to the excellent performances of the Advanced gamma-Tracking Array AGATA, coupled to the PARIS scintillator array and to the VAMOS++ magnetic spectrometer. The experimental lifetimes agree with predictions of ab initio calculations using two- and three-nucleon interactions, obtained with the valence-space in-medium similarity renormalization group for O-20 and with the no-core shell model for C-16. The present measurement shows the power of electromagnetic observables, determined with high-precision gamma spectroscopy, to assess the quality of first-principles nuclear structure calculations, complementing common benchmarks based on nuclear energies. The proposed experimental approach will be essential for short lifetime measurements in unexplored regions of the nuclear chart, including r-process nuclei, when intense beams, produced by Isotope Separation On-Line (ISOL) techniques, become available.
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| 11. |
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| 12. |
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| 13. |
- Koivula, Robert W., et al.
(författare)
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The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes : an IMI DIRECT study
- 2020
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Ingår i: Diabetologia. - : Springer Nature. - 0012-186X .- 1432-0428. ; 63:4, s. 744-756
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: It is well established that physical activity, abdominal ectopic fat and glycaemic regulation are related but the underlying structure of these relationships is unclear. The previously proposed twin-cycle hypothesis (TC) provides a mechanistic basis for impairment in glycaemic control through the interactions of substrate availability, substrate metabolism and abdominal ectopic fat accumulation. Here, we hypothesise that the effect of physical activity in glucose regulation is mediated by the twin-cycle. We aimed to examine this notion in the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) Consortium cohorts comprised of participants with normal or impaired glucose regulation (cohort 1: N ≤ 920) or with recently diagnosed type 2 diabetes (cohort 2: N ≤ 435). Methods: We defined a structural equation model that describes the TC and fitted this within the IMI DIRECT dataset. A second model, twin-cycle plus physical activity (TC-PA), to assess the extent to which the effects of physical activity in glycaemic regulation are mediated by components in the twin-cycle, was also fitted. Beta cell function, insulin sensitivity and glycaemic control were modelled from frequently sampled 75 g OGTTs (fsOGTTs) and mixed-meal tolerance tests (MMTTs) in participants without and with diabetes, respectively. Abdominal fat distribution was assessed using MRI, and physical activity through wrist-worn triaxial accelerometry. Results are presented as standardised beta coefficients, SE and p values, respectively. Results: The TC and TC-PA models showed better fit than null models (TC: χ2 = 242, p = 0.004 and χ2 = 63, p = 0.001 in cohort 1 and 2, respectively; TC-PA: χ2 = 180, p = 0.041 and χ2 = 60, p = 0.008 in cohort 1 and 2, respectively). The association of physical activity with glycaemic control was primarily mediated by variables in the liver fat cycle. Conclusions/interpretation: These analyses partially support the mechanisms proposed in the twin-cycle model and highlight mechanistic pathways through which insulin sensitivity and liver fat mediate the association between physical activity and glycaemic control.
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| 14. |
- Caceres, L., et al.
(författare)
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Nuclear structure studies of F-24
- 2015
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 92:1
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Tidskriftsartikel (refereegranskat)abstract
- The structure of the F-24 nucleus has been studied at GANIL using the beta decay of O-24 and the in-beam.-ray spectroscopy from the fragmentation of Na-27,Na-28, Ne-25,Ne-26, and Mg-29,Mg-30 nuclei. Combining these complementary experimental techniques, the level scheme of F-24 has been constructed up to 3.6 MeV by means of particle-gamma and particle-gamma gamma coincidence relations. Experimental results are compared to shell-model calculations using the standard USDA and USDB interactions as well as ab initio valence-space Hamiltonians calculated from the in-medium similarity renormalization group based on chiral two- and three-nucleon forces. Both methods reproduce the measured level spacings well, and this close agreement allows unidentified spins and parities to be consistently assigned.
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Brown, A.A., et al.
(författare)
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Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- We evaluate the shared genetic regulation of mRNA molecules, proteins and metabolites derived from whole blood from 3029 human donors. We find abundant allelic heterogeneity, where multiple variants regulate a particular molecular phenotype, and pleiotropy, where a single variant associates with multiple molecular phenotypes over multiple genomic regions. The highest proportion of share genetic regulation is detected between gene expression and proteins (66.6%), with a further median shared genetic associations across 49 different tissues of 78.3% and 62.4% between plasma proteins and gene expression. We represent the genetic and molecular associations in networks including 2828 known GWAS variants, showing that GWAS variants are more often connected to gene expression in trans than other molecular phenotypes in the network. Our work provides a roadmap to understanding molecular networks and deriving the underlying mechanism of action of GWAS variants using different molecular phenotypes in an accessible tissue. © 2023, Springer Nature Limited.
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| 19. |
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| 20. |
- Hagen, G., et al.
(författare)
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Neutron and weak-charge distributions of the Ca-48 nucleus
- 2016
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Ingår i: Nature Physics. - : Springer Science and Business Media LLC. - 1745-2481 .- 1745-2473. ; 12:2, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- What is the size of the atomic nucleus? This deceivably simple question is difficult to answer. Although the electric charge distributions in atomic nuclei were measured accurately already half a century ago, our knowledge of the distribution of neutrons is still deficient. In addition to constraining the size of atomic nuclei, the neutron distribution also impacts the number of nuclei that can exist and the size of neutron stars. We present an ab initio calculation of the neutron distribution of the neutron-rich nucleus Ca-48. We show that the neutron skin (difference between the radii of the neutron and proton distributions) is significantly smaller than previously thought. We also make predictions for the electric dipole polarizability and the weak form factor; both quantities that are at present targeted by precision measurements. Based on ab initio results for Ca-48, we provide a constraint on the size of a neutron star.
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| 21. |
- Korolija, D, et al.
(författare)
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Evaluation of quality of life after laparoscopic surgery: evidence-based guidelines of the European Association for Endoscopic Surgery.
- 2004
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Ingår i: Surgical Endoscopy. - : Springer Science and Business Media LLC. - 0930-2794 .- 1432-2218. ; 18:6, s. 879-897
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Tidskriftsartikel (refereegranskat)abstract
- Background Measuring health-related quality of life (QoL) after surgery is essential for decision making by patients, surgeons, and payers. The aim of this consensus conference was twofold. First, it was to determine for which diseases endoscopic surgery results in better postoperative QoL than open surgery. Second, it was to recommend QoL instruments for clinical research. Methods An expert panel selected 12 conditions in which QoL and endoscopic surgery are important. For each condition, studies comparing endoscopic and open surgery in terms of QoL were identified. The expert panel reached consensus on the relative benefits of endoscopic surgery and recommended generic and disease-specific QoL instruments for use in clinical research. Results Randomized trials indicate that QoL improves earlier after endoscopic than open surgery for gastroesophageal reflux disease (GERD), cholecystolithiasis, colorectal cancer, inguinal hernia, obesity (gastric bypass), and uterine disorders that require hysterectomy. For spleen, prostate, malignant kidney, benign colorectal, and benign non-GERD esophageal diseases, evidence from nonrandomized trials supports the use of laparoscopic surgery. However, many studies failed to collect long-term results, used nonvalidated questionnaires, or measured QoL components only incompletely. The following QoL instruments can be recommended: for benign esophageal and gallbladder disease, the GIQLI or the QOLRAD together with SF-36 or the PGWB; for obesity surgery, the IWQOL-Lite with the SF-36; for colorectal cancer, the FACT-C or the EORTC QLQ-C30/CR38; for inguinal and renal surgery, the VAS for pain with the SF-36 (or the EORTC QLQ-C30 in case of malignancy); and after hysterectomy, the SF-36 together with an evaluation of urinary and sexual function. Conclusions Laparoscopic surgery provides better postoperative QoL in many clinical situations. Researchers would improve the quality of future studies by using validated QoL instruments such as those recommended here.
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| 22. |
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| 23. |
- Rossi, C. A., et al.
(författare)
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Longitudinal Relationships Between Proteomics and Beta-Cell Dysfunction in Type 2 Diabetes: an IMI Direct Study
- 2023
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Ingår i: 8th National Congress of Bioengineering, GNB 2023. - : Patron Editore S.r.l..
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Konferensbidrag (refereegranskat)abstract
- β-cell dysfunction is a crucial factor of glycaemic deterioration in type 2 diabetes (T2D), but the role of circulating proteins in its progression is currently not understood. We studied the potential associations between β-cell glucose sensitivity progression over 3 years and baseline proteomics in a cohort of recently diagnosed T2D patients (N = 653) from the IMI-DIRECT project, through linear regression analysis. We found that forty-six proteins have a significant association to β-cell glucose sensitivity progression. Subsequent functional analysis showed these proteins belong to functional modules linked to insulin secretion and T2D pathophysiology. These findings, along with further investigation in longitudinal studies, may point to novel protein markers and processes of β-cell function deterioration.
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| 24. |
- Allesøe, Rosa Lundbye, et al.
(författare)
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Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models
- 2023
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Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 41:3, s. 399-408
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Tidskriftsartikel (refereegranskat)abstract
- The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug–omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug–drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities.
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| 25. |
- Bacca, S., et al.
(författare)
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Neutrino processes in partially degenerate neutron matter
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 758:1, s. 34-
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Tidskriftsartikel (refereegranskat)abstract
- We investigate neutrino processes for conditions reached in simulations of core-collapse supernovae. In regions where neutrino-matter interactions play an important role, matter is partially degenerate, and we extend earlier work that addressed the degenerate regime. We derive expressions for the spin structure factor in neutron matter, which is a key quantity required for evaluating rates of neutrino processes. We show that, for essentially all conditions encountered in the post-bounce phase of core-collapse supernovae, it is a very good approximation to calculate the spin relaxation rates in the nondegenerate limit. We calculate spin relaxation rates based on chiral effective field theory interactions and find that they are typically a factor of two smaller than those obtained using the standard one-pion-exchange interaction alone.
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