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1.
  • 2021
  • swepub:Mat__t
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  • 2021
  • swepub:Mat__t
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3.
  • Glasbey, JC, et al. (författare)
  • 2021
  • swepub:Mat__t
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  • Murari, A., et al. (författare)
  • A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
  • 2024
  • Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
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  • Reimerdes, H., et al. (författare)
  • Overview of the TCV tokamak experimental programme
  • 2022
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 62:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The tokamak a configuration variable (TCV) continues to leverage its unique shaping capabilities, flexible heating systems and modern control system to address critical issues in preparation for ITER and a fusion power plant. For the 2019-20 campaign its configurational flexibility has been enhanced with the installation of removable divertor gas baffles, its diagnostic capabilities with an extensive set of upgrades and its heating systems with new dual frequency gyrotrons. The gas baffles reduce coupling between the divertor and the main chamber and allow for detailed investigations on the role of fuelling in general and, together with upgraded boundary diagnostics, test divertor and edge models in particular. The increased heating capabilities broaden the operational regime to include T (e)/T (i) similar to 1 and have stimulated refocussing studies from L-mode to H-mode across a range of research topics. ITER baseline parameters were reached in type-I ELMy H-modes and alternative regimes with 'small' (or no) ELMs explored. Most prominently, negative triangularity was investigated in detail and confirmed as an attractive scenario with H-mode level core confinement but an L-mode edge. Emphasis was also placed on control, where an increased number of observers, actuators and control solutions became available and are now integrated into a generic control framework as will be needed in future devices. The quantity and quality of results of the 2019-20 TCV campaign are a testament to its successful integration within the European research effort alongside a vibrant domestic programme and international collaborations.
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13.
  • Pucella, G., et al. (författare)
  • Overview of the FTU results
  • 2022
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 62:4
  • Forskningsöversikt (refereegranskat)abstract
    • Since the 2018 IAEA FEC Conference, FTU operations have been devoted to several experiments covering a large range of topics, from the investigation of the behaviour of a liquid tin limiter to the runaway electrons mitigation and control and to the stabilization of tearing modes by electron cyclotron heating and by pellet injection. Other experiments have involved the spectroscopy of heavy metal ions, the electron density peaking in helium doped plasmas, the electron cyclotron assisted start-up and the electron temperature measurements in high temperature plasmas. The effectiveness of the laser induced breakdown spectroscopy system has been demonstrated and the new capabilities of the runaway electron imaging spectrometry system for in-flight runaways studies have been explored. Finally, a high resolution saddle coil array for MHD analysis and UV and SXR diamond detectors have been successfully tested on different plasma scenarios.
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14.
  • Sartelli, Massimo, et al. (författare)
  • Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action
  • 2023
  • Ingår i: WORLD JOURNAL OF EMERGENCY SURGERY. - 1749-7922. ; 18:1
  • Forskningsöversikt (refereegranskat)abstract
    • Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or "golden rules," for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice.
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15.
  • Esposito, B., et al. (författare)
  • Progress of Design and Development for the ITER Radial Neutron Camera
  • 2022
  • Ingår i: Journal of fusion energy. - : Springer. - 0164-0313 .- 1572-9591. ; 41:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The paper presents an overview of the design status of the Radial Neutron Camera (RNC), that, together with the Vertical Neutron Camera, will provide, through reconstruction techniques applied to the measured line-integrated neutron fluxes, the time resolved measurement of the ITER neutron and alpha-source profile (i.e. neutron emissivity, neutrons emitted per unit time and volume). The RNC is composed of two subsystems, the In-Port RNC and Ex-Port RNC located, respectively, inside and outside the Plug of Equatorial Port #01. The In-Port subsystem is in a more advanced design stage since it has recently undergone the Final Design Review in the ITER procurement process. The paper describes the diagnostic layout, the interfaces, the measurement capabilities and the main challenges in its realization. Prototyping and testing of neutron detectors and electronics components were carried out and led to the choice of the component solutions that can match the environmental and operational constraints in terms radiation hardness, high temperature and electromagnetic compatibility. The performance of the RNC in terms of neutron emissivity measurement capability was assessed through 1D and 2D reconstruction analysis. It is proven that the neutron emissivity can be reconstructed in real-time within the measurement requirements: 10% accuracy, 10 ms time resolution and a/10 (a = plasma minor radius) space resolution.
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16.
  • Graham, N. S. N., et al. (författare)
  • Axonal marker neurofilament light predicts long-term outcomes and progressive neurodegeneration after traumatic brain injury
  • 2021
  • Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 13:613
  • Tidskriftsartikel (refereegranskat)abstract
    • Axonal injury is a key determinant of long-term outcomes after traumatic brain injury (TBI) but has been difficult to measure clinically. Fluid biomarker assays can now sensitively quantify neuronal proteins in blood. Axonal components such as neurofilament light (NfL) potentially provide a diagnostic measure of injury. In the multicenter BIO-AX-TBI study of moderate-severe TBI, we investigated relationships between fluid biomarkers, advanced neuroimaging, and clinical outcomes. Cerebral microdialysis was used to assess biomarker concentrations in brain extracellular fluid aligned with plasma measurement. An experimental injury model was used to validate biomarkers against histopathology. Plasma NfL increased after TBI, peaking at 10 days to 6 weeks but remaining abnormal at 1 year. Concentrations were around 10 times higher early after TBI than in controls (patients with extracranial injuries). NfL concentrations correlated with diffusion MRI measures of axonal injury and predicted white matter neurodegeneration. Plasma TAU predicted early gray matter atrophy. NfL was the strongest predictor of functional outcomes at 1 year. Cerebral microdialysis showed that NfL concentrations in plasma and brain extracellular fluid were highly correlated. An experimental injury model confirmed a dose-response relationship of histopathologically defined axonal injury to plasma NfL. In conclusion, plasma NfL provides a sensitive and clinically meaningful measure of axonal injury produced by TBI. This reflects the extent of underlying damage, validated using advanced MRI, cerebral microdialysis, and an experimental model. The results support the incorporation of NfL sampling subacutely after injury into clinical practice to assist with the diagnosis of axonal injury and to improve prognostication.
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  • Spartà, R., et al. (författare)
  • 8B reaction dynamics researched at HIE-ISOLDE
  • 2024
  • Ingår i: Nuovo Cimento della Societa Italiana di Fisica C. - 2037-4909 .- 1826-9885. ; 47:2
  • Tidskriftsartikel (refereegranskat)abstract
    • For the first time a measurement of 8B + 64Zn reaction has been performed at HIE-ISOLDE at CERN at energies around the Coulomb barrier, to understand how the debated halo structure of the light nucleus can affect reaction dynamics.
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  • Spartà, R., et al. (författare)
  • Probing proton halo effects in the 8 B+ 64 Zn collision around the Coulomb barrier
  • 2021
  • Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 820
  • Tidskriftsartikel (refereegranskat)abstract
    • Proton halo effects in the 8B+64Zn reaction at an energy around 1.5 times the Coulomb barrier have been studied at HIE-ISOLDE CERN using, for the first time, the only existing postaccelerated 8B beam. This, together with the use of a high granularity and large solid angle detection system, allowed for a careful mapping of the elastic angular distribution, especially in the Coulomb-nuclear interference region. Contrary to what is observed for the one-neutron halo nucleus 11Be on the same target in a similar energy range, the analysis of the elastic scattering angular distribution shows only a modest suppression of the Coulomb-nuclear interference peak, with no remarkable enhancement of the total reaction cross-section. Inclusive angular and energy distributions of 7Be produced in direct reaction processes have also been measured. The comparison of these data with the results of theoretical calculations for the elastic and non-elastic breakup contributions indicate that both processes are important. Overall, the experimental data suggest a 8B collision dynamics at the barrier very different from the one of neutron halo nuclei, showing only modest effects of coupling to continuum. This behaviour can be interpreted as due to the presence of the additional Coulomb interactions halo-core and halo-target together with the presence of the centrifugal barrier felt by the valence proton of 8B.
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20.
  • Tristao-Pereira, C., et al. (författare)
  • Longitudinal interplay between subclinical atherosclerosis, cardiovascular risk factors, and cerebral glucose metabolism in midlife: results from the PESA prospective cohort study
  • 2023
  • Ingår i: Lancet Healthy Longevity. - 2666-7568. ; 4:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Cardiovascular disease and dementia often coexist at advanced stages. Yet, longitudinal studies examining the interplay between atherosclerosis and its risk factors on brain health in midlife are scarce. We aimed to characterise the longitudinal associations between cerebral glucose metabolism, subclinical atherosclerosis, and cardiovascular risk factors in middle-aged asymptomatic individuals. Methods The Progression of Early Subclinical Atherosclerosis (PESA) study is a Spanish longitudinal observational cohort study of 4184 asymptomatic individuals aged 40-54 years (NCT01410318). Participants with subclinical atherosclerosis underwent longitudinal cerebral [18F]fluorodeoxyglucose ([18F]FDG)-PET, and annual percentage change in [18F]FDG uptake was assessed (primary outcome). Cardiovascular risk was quantified with SCORE2 and subclinical atherosclerosis with three-dimensional vascular ultrasound (exposures). Multivariate regression and linear mixed effects models were used to assess associations between outcomes and exposures. Additionally, blood based biomarkers of neuropathology were quantified and mediation analyses were performed. Secondary analyses were corrected for multiple comparisons using the false discovery rate (FDR) approach. Findings This longitudinal study included a PESA subcohort of 370 participants (median age at baseline 49 & BULL;8 years [IQR 46 & BULL;1-52 & BULL;2]; 309 [84%] men, 61 [16%] women; median follow-up 4 & BULL;7 years [IQR 4 & BULL;2-5 & BULL;2]). Baseline scans took place between March 6, 2013, and Jan 21, 2015, and follow-up scans between Nov 24, 2017, and Aug 7, 2019. Persistent high risk of cardiovascular disease was associated with an accelerated decline of cortical [18F]FDG uptake compared with low risk (& beta;=-0 & BULL;008 [95% CI -0 & BULL;013 to -0 & BULL;002]; pFDR=0 & BULL;040), with plasma neurofilament light chain, a marker of neurodegeneration, mediating this association by 20% (& beta;=0 & BULL;198 [0 & BULL;008 to 0 & BULL;740]; pFDR=0 & BULL;050). Moreover, progression of subclinical carotid atherosclerosis was associated with an additional decline in [18F]FDG uptake in Alzheimer's disease brain regions, not explained by cardiovascular risk (& beta;=-0 & BULL;269 [95% CI -0 & BULL;509 to -0 & BULL;027]; p=0 & BULL;029). Interpretation Middle-aged asymptomatic individuals with persistent high risk of cardiovascular disease and subclinical carotid atherosclerosis already present brain metabolic decline, suggesting that maintenance of cardiovascular health during midlife could contribute to reductions in neurodegenerative disease burden later in life.
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  • Graham, N., et al. (författare)
  • Alzheimer's disease marker phospho-tau181 is not elevated in the first year after moderate-to-severe TBI
  • 2024
  • Ingår i: Journal of Neurology Neurosurgery and Psychiatry. - 0022-3050. ; 95:4, s. 356-359
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundTraumatic brain injury (TBI) is associated with the tauopathies Alzheimer's disease and chronic traumatic encephalopathy. Advanced immunoassays show significant elevations in plasma total tau (t-tau) early post-TBI, but concentrations subsequently normalise rapidly. Tau phosphorylated at serine-181 (p-tau181) is a well-validated Alzheimer's disease marker that could potentially seed progressive neurodegeneration. We tested whether post-traumatic p-tau181 concentrations are elevated and relate to progressive brain atrophy.MethodsPlasma p-tau181 and other post-traumatic biomarkers, including total-tau (t-tau), neurofilament light (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), were assessed after moderate-to-severe TBI in the BIO-AX-TBI cohort (first sample mean 2.7 days, second sample within 10 days, then 6 weeks, 6 months and 12 months, n=42). Brain atrophy rates were assessed in aligned serial MRI (n=40). Concentrations were compared patients with and without Alzheimer's disease, with healthy controls.ResultsPlasma p-tau181 concentrations were significantly raised in patients with Alzheimer's disease but not after TBI, where concentrations were non-elevated, and remained stable over one year. P-tau181 after TBI was not predictive of brain atrophy rates in either grey or white matter. In contrast, substantial trauma-associated elevations in t-tau, NfL, GFAP and UCH-L1 were seen, with concentrations of NfL and t-tau predictive of brain atrophy rates.ConclusionsPlasma p-tau181 is not significantly elevated during the first year after moderate-to-severe TBI and levels do not relate to neuroimaging measures of neurodegeneration.
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22.
  • Pietro, A Di, et al. (författare)
  • Proton halo effects in the 8B+64Zn collision around the Coulomb barrier
  • 2023
  • Ingår i: Journal of Physics: Conference Series. - 1742-6596 .- 1742-6588. ; 2586:1, s. 012079-012079
  • Tidskriftsartikel (refereegranskat)abstract
    • The 8B+64Zn reaction at 38.5 MeV has been studied at HIE-ISOLDE CERN to investigate proton halo effect on the reaction dynamics. For the first time it was used the only existing post-accelerated 8B beam. The measured elastic scattering angular distribution showed a small suppression of the Coulomb-nuclear interference peak, opposite to what observed for the one-neutron halo nucleus 11Be on the same target where a large suppression was observed instead. Inclusive angular and energy distributions of breakup fragments were also measured showing that, both, elastic and non-elastic breakup contribute. The presence of the additional Coulomb interactions halo-core and halo-target in 8B makes the reaction dynamics in this proton-halo nucleus different than the neutron-halo case. © 2023 Institute of Physics Publishing. All rights reserved.
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  • Ali, Sk M., et al. (författare)
  • Study of the 7Be(d,3He)6Li* reaction at 5 MeV/u
  • 2024
  • Ingår i: Physics Letters B. - 0370-2693. ; 853
  • Tidskriftsartikel (refereegranskat)abstract
    • The measurement of the 7Be(d,3He)6Li* transfer cross section at 5 MeV/u is carried out. The population of the 2.186 MeV excited state of 6Li in this reaction channel is observed for the first time. The experimental angular distributions have been analyzed in the finite range DWBA and coupled-channel frameworks. The effect of the 7Be(d,3He)6Li reaction on both the 6Li and 7Li abundances are investigated at the relevant big-bang nucleosynthesis energies. The excitation function is calculated by TALYS and normalized to the experimental data. The S factor of the (d,3He) channel from the present work is about 50% lower than existing data at nearby energies. At big-bang energies, the S factor is about three orders of magnitude smaller than that of the (d,p) channel. The (d,3He) reaction rate is found to have a less than 0.1% effect on the 6,7Li abundances.
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28.
  • Chow, LS, et al. (författare)
  • Reply to 'Lactate as a major myokine and exerkine'
  • 2022
  • Ingår i: Nature reviews. Endocrinology. - : Springer Science and Business Media LLC. - 1759-5037 .- 1759-5029. ; 18:11, s. 713-713
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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  • Kundalia, K., et al. (författare)
  • Study of elastic and inelastic scattering of 7Be + 12C at 35 MeV
  • 2022
  • Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693. ; 833, s. 137294-137294
  • Tidskriftsartikel (refereegranskat)abstract
    • The elastic and inelastic scattering of 7Be from 12C have been measured at an incident energy of 35 MeV. The inelastic scattering leading to the 4.439 MeV excited state of 12C has been measured for the first time. The experimental data cover an angular range of θcm = 15∘-120∘. Optical model analyses were carried out with Woods-Saxon and double-folding potential using the density dependent M3Y (DDM3Y) effective interaction. The microscopic analysis of the elastic data indicates breakup channel coupling effect. A coupled-channel analysis of the inelastic scattering, based on collective form factors, shows that mutual excitation of both 7Be and 12C is significantly smaller than the single excitation of 12C. The larger deformation length obtained from the DWBA analysis could be explained by including the excitation of 7Be in a coupled-channel analysis. The breakup cross section of 7Be is estimated to be less than 10% of the reaction cross section. The intrinsic deformation length obtained for the 12C⁎ (4.439 MeV) state is δ2 = 1.37 fm. The total reaction cross section deduced from the analysis agrees very well with Wong's calculations for similar weakly bound light nuclei on 12C target.
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  • Li, L. M., et al. (författare)
  • Investigating the characteristics and correlates of systemic inflammation after traumatic brain injury: the TBI-BraINFLAMM study
  • 2023
  • Ingår i: Bmj Open. - 2044-6055. ; 13:5
  • Tidskriftsartikel (refereegranskat)abstract
    • IntroductionA significant environmental risk factor for neurodegenerative disease is traumatic brain injury (TBI). However, it is not clear how TBI results in ongoing chronic neurodegeneration. Animal studies show that systemic inflammation is signalled to the brain. This can result in sustained and aggressive microglial activation, which in turn is associated with widespread neurodegeneration. We aim to evaluate systemic inflammation as a mediator of ongoing neurodegeneration after TBI.Methods and analysisTBI-braINFLAMM will combine data already collected from two large prospective TBI studies. The CREACTIVE study, a broad consortium which enrolled >8000 patients with TBI to have CT scans and blood samples in the hyperacute period, has data available from 854 patients. The BIO-AX-TBI study recruited 311 patients to have acute CT scans, longitudinal blood samples and longitudinal MRI brain scans. The BIO-AX-TBI study also has data from 102 healthy and 24 non-TBI trauma controls, comprising blood samples (both control groups) and MRI scans (healthy controls only). All blood samples from BIO-AX-TBI and CREACTIVE have already been tested for neuronal injury markers (GFAP, tau and NfL), and CREACTIVE blood samples have been tested for inflammatory cytokines. We will additionally test inflammatory cytokine levels from the already collected longitudinal blood samples in the BIO-AX-TBI study, as well as matched microdialysate and blood samples taken during the acute period from a subgroup of patients with TBI (n=18).We will use this unique dataset to characterise post-TBI systemic inflammation, and its relationships with injury severity and ongoing neurodegeneration.Ethics and disseminationEthical approval for this study has been granted by the London-Camberwell St Giles Research Ethics Committee (17/LO/2066). Results will be submitted for publication in peer-review journals, presented at conferences and inform the design of larger observational and experimental medicine studies assessing the role and management of post-TBI systemic inflammation.
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  • Ciccarone, F., et al. (författare)
  • Imaging in gynecological disease (23) : clinical and ultrasound characteristics of ovarian carcinosarcoma
  • 2022
  • Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 59:2, s. 241-247
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To describe the clinical and ultrasound characteristics of ovarian carcinosarcoma. Methods: This was a retrospective multicenter study. Patients with a histological diagnosis of ovarian carcinosarcoma, who had undergone preoperative ultrasound examination between 2010 and 2019, were identified from the International Ovarian Tumor Analysis (IOTA) database. Additional patients who were examined outside of the IOTA study were identified from the databases of the participating centers. The masses were described using the terms and definitions of the IOTA group. Additionally, two experienced ultrasound examiners reviewed all available images to identify typical ultrasound features using pattern recognition. Results: Ninety-one patients with ovarian carcinosarcoma who had undergone ultrasound examination were identified, of whom 24 were examined within the IOTA studies and 67 were examined outside of the IOTA studies. Median age at diagnosis was 66 (range, 33–91) years and 84/91 (92.3%) patients were postmenopausal. Most patients (67/91, 73.6%) were symptomatic, with the most common complaint being pain (51/91, 56.0%). Most tumors (67/91, 73.6%) were International Federation of Gynecology and Obstetrics (FIGO) Stage III or IV. Bilateral lesions were observed on ultrasound in 46/91 (50.5%) patients. Ascites was present in 38/91 (41.8%) patients. The median largest tumor diameter was 100 (range, 18–260) mm. All ovarian carcinosarcomas contained solid components, and most were described as solid (66/91, 72.5%) or multilocular-solid (22/91, 24.2%). The median diameter of the largest solid component was 77.5 (range, 11–238) mm. Moderate or rich vascularization was found in 78/91 (85.7%) cases. Retrospective analysis of ultrasound images and videoclips using pattern recognition in 73 cases revealed that all tumors had irregular margins and inhomogeneous echogenicity of the solid components. Forty-seven of 73 (64.4%) masses appeared as a solid tumor with cystic areas. Cooked appearance of the solid tissue was identified in 28/73 (38.4%) tumors. No pathognomonic ultrasound sign of ovarian carcinosarcoma was found. Conclusions: Ovarian carcinosarcomas are usually diagnosed in postmenopausal women and at an advanced stage. The most common ultrasound appearance is a large solid tumor with irregular margins, inhomogeneous echogenicity of the solid tissue and cystic areas. The second most common pattern is a large multilocular-solid mass with inhomogeneous echogenicity of the solid tissue.
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35.
  • Cupak, C., et al. (författare)
  • Absence of synergistic effects in quasi-simultaneous sputtering of tungsten by Ar and D ions
  • 2023
  • Ingår i: Nuclear Materials and Energy. - : Elsevier. - 2352-1791. ; 35
  • Tidskriftsartikel (refereegranskat)abstract
    • A quartz crystal microbalance was used to experimentally study the erosion of tungsten during rapidly alternating bombardment with 2 keV argon and deuterium projectiles. A key goal was to investigate whether the mean sputtering yield of the alternating irradiation can be predicted from data for sputtering yields of single ion species. In addition, influences by residual gas pressure in the UHV experiment and variable ion fluxes have been studied. Our results show that the mean sputtering yield of irradiations with alternating ion species can be well predicted for a range of different fluence ratios as a simple superposition of individual sputtering yields, weighted by the respective relative fluences. This finding supports that no synergistic sputtering effects were relevant in the investigated low-flux regime.
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36.
  • Cupak, C., et al. (författare)
  • Sputter yields of rough surfaces : Importance of the mean surface inclination angle from nano- to microscopic rough regimes
  • 2021
  • Ingår i: Applied Surface Science. - : Elsevier. - 0169-4332 .- 1873-5584. ; 570
  • Tidskriftsartikel (refereegranskat)abstract
    • The roughness of a surface is known to have a strong influence on the sputtering process. Commonly used 1D Monte Carlo codes for calculating sputter yields show good agreement with experimental data only for comparably flat surfaces, whereas local ion incidence angles, shadowing and redeposition influence the sputter yields in both magnitude and angular dependence on rough surfaces. In the present work, we therefore investigated tungsten samples of largely different roughness, characterised by atomic force and confocal microscopy. A highly sensitive quartz crystal microbalance was used to determine sputter yields during ion irradiation. Low ion fluences were applied to ensure that the surface morphology did not change during irradiation. The results were used to benchmark our new ray-tracing simulation code SPRAY, which can take microscopy images without limitations in size as input. SPRAY was furthermore applied to perform systematic simulations for artificially roughened and computer-generated surfaces. A clear result was that the governing parameter for description of the sputtering behaviour is the mean value of the surface inclination angle distribution, rather than the commonly used root mean square roughness. Our simulations show that this parameter is universally applicable for a wide range of different surface structures.
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41.
  • Bergstrom, A, et al. (författare)
  • Severe liver disease resembling PSC in mice with K5-Cre mediated deletion of Krüppel-like factor 5 (Klf5)
  • 2021
  • Ingår i: Transgenic research. - : Springer Science and Business Media LLC. - 1573-9368 .- 0962-8819. ; 30:5, s. 701-707
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic cholestatic liver diseases including primary sclerosing cholangitis (PSC) present a complex spectrum with regards to the cause, age of manifestation and histopathological features. Current treatment options are severely limited primarily due to a paucity of model systems mirroring the disease. Here, we describe the Keratin 5 (K5)-Cre; Klf5fl/fl mouse that spontaneously develops severe liver disease during the postnatal period with features resembling PSC including a prominent ductular reaction, fibrotic obliteration of the bile ducts and secondary degeneration/necrosis of liver parenchyma. Over time, there is an expansion of Sox9+ hepatocytes in the damaged livers suggestive of a hepatocyte-mediated regenerative response. We conclude that Klf5 is required for the normal function of the hepatobiliary system and that the K5-Cre; Klf5fl/fl mouse is an excellent model to probe the molecular events interlinking damage and regenerative response in the liver.
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42.
  • Correa, S. A., et al. (författare)
  • A multipurpose set-up using keV ions for nuclear reaction analysis, high -resolution backscattering spectrometry, low-energy PIXE and in-situ irradiation experiments
  • 2020
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section B. - : ELSEVIER. - 0168-583X .- 1872-9584. ; 478, s. 104-110
  • Tidskriftsartikel (refereegranskat)abstract
    • A new chamber for material analysis and modification using energetic ions with primary particle energies in the keV regime was developed at the single stage 350 kV high-current Danfysik implanter at the Tandem Laboratory, Uppsala University. The experimental set-up allows for B-11 and O-18 depth profiling by Nuclear Reaction Analysis using the B-11(p,alpha(0))Be-8 and O-18(p,alpha)N-15 nuclear resonances at 163 keV and at 151 keV, respectively. Additionally, a surface barrier detector with a cryogenic assembly enables High-Resolution Backscattering Spectrometry with average resolution approximate to 4 keV FWHM for protons. A silicon drift detector enables Low-Energy Particle Induced X-ray Emission analysis for elements with low atomic number (Z >= 8). The available instrumentation of the chamber assembly with its specifications are described in details with a series of applied and fundamental benchmark studies, together with some suggestions for future applications.
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  • Gorchs, L, et al. (författare)
  • The vitamin D analogue calcipotriol promotes an anti-tumorigenic phenotype of human pancreatic CAFs but reduces T cell mediated immunity
  • 2020
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 17444-
  • Tidskriftsartikel (refereegranskat)abstract
    • The pancreatic tumour stroma is composed of phenotypically heterogenous cancer-associated fibroblasts (CAFs) with both pro- and anti-tumorigenic functions. Here, we studied the impact of calcipotriol, a vitamin D3 analogue, on the activation of human pancreatic CAFs and T cells using 2- and 3-dimensional (2D, 3D) cell culture models. We found that calcipotriol decreased CAF proliferation and migration and reduced the release of the pro-tumorigenic factors prostaglandin E2, IL-6, periostin, and leukemia inhibitory factor. However, calcipotriol promoted PD-L1 upregulation, which could influence T cell mediated tumour immune surveillance. Calcipotriol reduced T cell proliferation and production of IFN-γ, granzyme B and IL-17, but increased IL-10 secretion. These effects were even more profound in the presence of CAFs in 2D cultures and in the presence of CAFs and pancreatic tumour cell line (PANC-1) spheroids in 3D cultures. Functional assays on tumour infiltrating lymphocytes also showed a reduction in T cell activation by calcipotriol. This suggests that calcipotriol reduces the tumour supportive activity of CAFs but at the same time reduces T cell effector functions, which could compromise the patients’ tumour immune surveillance. Thus, vitamin D3 analogues appear to have dual functions in the context of pancreatic cancer, which could have important clinical implications.
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45.
  • Graham, Neil Samuel Nyholm, et al. (författare)
  • Multicentre longitudinal study of fluid and neuroimaging BIOmarkers of AXonal injury after traumatic brain injury: the BIO-AX-TBI study protocol.
  • 2020
  • Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 10:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Traumatic brain injury (TBI) often results in persistent disability, due particularly to cognitive impairments. Outcomes remain difficult to predict but appear to relate to axonal injury. Several new approaches involving fluid and neuroimaging biomarkers show promise to sensitively quantify axonal injury. By assessing these longitudinally in a large cohort, we aim both to improve our understanding of the pathophysiology of TBI, and provide better tools to predict clinical outcome.BIOmarkers of AXonal injury after TBI is a prospective longitudinal study of fluid and neuroimaging biomarkers of axonal injury after moderate-to-severe TBI, currently being conducted across multiple European centres. We will provide a detailed characterisation of axonal injury after TBI, using fluid (such as plasma/microdialysate neurofilament light) and neuroimaging biomarkers (including diffusion tensor MRI), which will then be related to detailed clinical, cognitive and functional outcome measures. We aim to recruit at least 250 patients, including 40 with cerebral microdialysis performed, with serial assessments performed twice in the first 10 days after injury, subacutely at 10 days to 6weeks, at 6 and 12 months after injury.The relevant ethical approvals have been granted by the following ethics committees: in London, by the Camberwell St Giles Research Ethics Committee; in Policlinico (Milan), by the Comitato Etico Milano Area 2; in Niguarda (Milan), by the Comitato Etico Milano Area 3; in Careggi (Florence), by the Comitato Etico Regionale per la Sperimentazione Clinica della Regione Toscana, Sezione area vasta centro; in Trento, by the Trento Comitato Etico per le Sperimentazioni Cliniche, Azienda Provinciale per i Servizi Sanitari della Provincia autonoma di Trento; in Lausanne, by the Commission cantonale d'éthique de la recherche sur l'être humain; in Ljubljana, by the National Medical Ethics Committee at the Ministry of Health of the Republic of Slovenia. The study findings will be disseminated to patients, healthcare professionals, academics and policy-makers including through presentation at conferences and peer-reviewed publications. Data will be shared with approved researchers to provide further insights for patient benefit.NCT03534154.
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46.
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47.
  • Kamp, JC, et al. (författare)
  • Fibrosis-Related Gene Profiling in Liver Biopsies of PiZZ α1-Antitrypsin Children with Different Clinical Courses
  • 2023
  • Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 24:3
  • Tidskriftsartikel (refereegranskat)abstract
    • PiZZ (Glu342Lys) α1-antitrypsin deficiency (AATD) is characterized by intrahepatic AAT polymerization and is a risk factor for liver disease development in children. The majority of PiZZ children are disease free, hence this mutation alone is not sufficient to cause the disease. We investigated Z-AAT polymers and the expression of fibrosis-related genes in liver tissues of PiZZ children with different clinical courses. Liver biopsies obtained during 1979–2010 at the Department of Paediatrics, Karolinska University Hospital, Sweden, were subjected to histological re-evaluation, immunohistochemistry and NanoString-based transcriptome profiling using a panel of 760 fibrosis plus 8 bile acid-related genes. Subjects were divided into three groups based on clinical outcomes: NCH (neonatal cholestasis, favourable outcome, n = 5), NCC (neonatal cholestasis, early cirrhosis and liver transplantation, n = 4), and NNCH (no neonatal cholestasis, favourable outcome, n = 5, six biopsies). Hepatocytes containing Z-AAT polymers were abundant in all groups whereas NCC showed higher expression of genes related to liver fibrosis/cirrhosis and lower expression of genes related to lipid, aldehyde/ketone, and bile acid metabolism. Z-AAT accumulation per se cannot explain the clinical outcomes of PiZZ children; however, changes in the expression of specific genes and pathways involved in lipid, fatty acid, and steroid metabolism appear to reflect the degree of liver injury.
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48.
  • Moro, F., et al. (författare)
  • Imaging in gynecological disease (20) : clinical and ultrasound characteristics of adnexal torsion
  • 2020
  • Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 56:6, s. 934-943
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To describe the clinical and ultrasound characteristics of adnexal torsion. Methods: This was a retrospective study. From the operative records of the eight participating gynecological ultrasound centers, we identified patients with a surgically confirmed diagnosis of adnexal torsion, defined as surgical evidence of ovarian pedicle, paraovarian cyst and/or Fallopian tube twisted on its own axis, who had undergone preoperative ultrasound examination by an experienced examiner, between 2008 and 2018. Only cases with at least two available ultrasound images and/or videoclips (one grayscale and one with Doppler evaluation) were included. Clinical, ultrasound, surgical and histological information was retrieved from each patient's medical record and entered into an Excel file by the principal investigator at each center. In addition, two authors reviewed all available ultrasound images and videoclips of the twisted adnexa, with regard to the presence of four predefined ultrasound features reported to be characteristic of adnexal torsion: (1) ovarian stromal edema with or without peripherally displaced antral follicles, (2) the follicular ring sign, (3) the whirlpool sign and (4) absence of vascularization in the twisted organ. Results: A total of 315 cases of adnexal torsion were identified. The median age of the patients was 30 (range, 1–88) years. Most patients were premenopausal (284/314; 90.4%) and presented with acute or subacute pelvic pain (305/315; 96.8%). The surgical approach was laparoscopic in 239/312 (76.6%) patients and conservative surgery (untwisting with or without excision of a lesion) was performed in 149/315 (47.3%) cases. According to the original ultrasound reports, the median largest diameter of the twisted organ was 83 (range, 30–349) mm. Free fluid in the pouch of Douglas was detected in 196/275 (71.3%) patients. Ovarian stromal edema with or without peripherally displaced antral follicles was reported in the original ultrasound report in 167/241 (69.3%) patients, the whirlpool sign in 178/226 (78.8%) patients, absent color Doppler signals in the twisted organ in 119/269 (44.2%) patients and the follicular ring sign in 51/134 (38.1%) patients. On retrospective review of images and videoclips, ovarian stromal edema with or without peripherally displaced antral follicles (201/254; 79.1%) and the whirlpool sign (139/153; 90.8%) were the most commonly detected features of adnexal torsion. Conclusion: Most patients with surgically confirmed adnexal torsion are of reproductive age and present with acute or subacute pain. Common ultrasound signs are an enlarged adnexa, the whirlpool sign, ovarian stromal edema with or without peripherally displaced antral follicles and free fluid in the pelvis. The follicular ring sign and absence of Doppler signals in the twisted organ are slightly less common signs. Recognizing ultrasound signs of adnexal torsion is important so that the correct treatment, i.e. surgery without delay, can be offered.
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49.
  • Moro, F., et al. (författare)
  • Imaging in gynecological disease (22) : clinical and ultrasound characteristics of ovarian embryonal carcinomas, non-gestational choriocarcinomas and malignant mixed germ cell tumors
  • 2021
  • Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 57:6, s. 987-994
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To describe the clinical and ultrasound characteristics of three types of rare malignant ovarian germ cell tumor: embryonal carcinoma, non-gestational choriocarcinoma and malignant mixed germ cell tumor. Methods: This was a retrospective multicenter study. From the International Ovarian Tumor Analysis (IOTA) database, we identified patients with a histological diagnosis of ovarian embryonal carcinoma, non-gestational choriocarcinoma or malignant mixed germ cell tumor, who had undergone preoperative ultrasound examination by an experienced ultrasound examiner between 2000 and 2020. Additional patients with the same histology were identified from the databases of the departments of gynecological oncology in the participating centers. All tumors were described using IOTA terminology. Three examiners reviewed all available ultrasound images and described them using pattern recognition. Results: One patient with embryonal carcinoma, five patients with non-gestational ovarian choriocarcinoma and seven patients with ovarian malignant mixed germ cell tumor (six primary tumors and one recurrence) were identified. Seven patients were included in the IOTA studies and six patients were examined outside of the IOTA studies. The median age at diagnosis was 26 (range, 14–77) years. Beta-human chorionic gonadotropin levels were highest in non-gestational choriocarcinomas and alpha-fetoprotein levels were highest in malignant mixed germ cell tumors. Most tumors were International Federation of Gynecology and Obstetrics (FIGO) Stage I (9/12 (75.0%)). All tumors were unilateral, and the median largest diameter was 129 (range, 38–216) mm. Of the tumors, 11/13 (84.6%) were solid and 2/13 (15.4%) were multilocular-solid; 9/13 (69.2%) manifested abundant vascularization on color Doppler examination. Using pattern recognition, the typical ultrasound appearance was a large solid tumor with inhomogeneous echogenicity of the solid tissue and often dispersed cysts which, in most cases, were small and irregular. Some tumors had smooth contours while others had irregular contours. Conclusions: A unilateral, large solid tumor with inhomogeneous echogenicity of the solid tissue and with dispersed small cystic areas in a young woman should raise the suspicion of a rare malignant germ cell tumor. This suspicion can guide the clinician to test tumor markers specific for malignant germ cell tumors.
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