Characterization of scintillator screens under irradiation of low energy 133Cs ions

An imaging heavy ion beam probe (i-HIBP) diagnostic, for the simultaneous measurement of plasma density, magnetic field and electrostatic potential in the plasma edge, has been installed at ASDEX Upgrade. Unlike standard heavy ion beam probes, in the i-HIBP the probing (heavy) ions are collected by a scintillator detector, creating a light pattern or strike-line, which is then imaged by a camera. Therefore, a good characterization of the scintillator response is needed. Previous works focused on the scintillator behaviour against irradiation with light ions such as hydrogen and alpha particles. In this work we present the characterization of several scintillator screens — TG-Green (SrGa2S4:Eu2+), YAG-Ce (Y3Al5O12:Ce3+) and P11 (ZnS:Ag) — against irradiation with 133Cs+ ions, in an energy range between 5 and 70 keV and ion currents between 105 and 107ions/(s·cm2). Three main properties of the scintillators have been studied: the ionolumenescence efficiency or yield, the linearity and the degradation as a function of the fluence. The highest yield was delivered by the TG-Green scintillator screen with > 8·103 photons/ion at 50 keV. All the samples showed a linear response with increasing incident ion flux. The degradation was quantified in terms of the fluence F1/2, which leads to a reduction of the emissivity by a factor of 2. TG-Green showed the lowest degradation with F1/2= 5.4·1014ions/cm2. After the irradiation the samples were analyzed by Scanning Electron Microscopy (SEM), Rutherford Backscattering Spectrometry (RBS) and Particle Induced X-ray Emission (PIXE). No trace of Cs was found in the irradiated regions. These results indicate that, among the tested materials, TG-Green is the best candidate for the i-HIBP detector.European Union’s Horizon 2020 (grant agreement No. 805162)Helmholtz Association VHNG-1350Spanish Ministry of Science and Innovation FJC2019-041092-I

Chaperoned amyloid proteins for immune manipulation: A-synuclein/hsp70 shifts immunity toward a modulatory phenotype

a-Synuclein (aSyn) is a 140-residue amyloid-forming protein whose aggregation is linked to Parkinson’s disease (PD). It has also been found to play a critical role in the immune imbalance that accompanies disease progression, a characteristic that has prompted the search for an effective aSyn-based immunotherapy. In this study, we have simultaneously exploited two important features of certain heat-shock proteins (HSPs): their classical ‘‘chaperone’’ activities and their recently discovered and diverse ‘‘immunoactive’’ properties. In particular, we have explored the immune response elicited by immunization of C57BL/6 mice with an aSyn/Hsp70 protein combination in the absence of added adjuvant. Our results show differential effects for mice immunized with the aSyn/Hsp70 complex, including a restrained aSyn-specific (IgM and IgG) humoral response as well as minimized alterations in the Treg (CD4 CD25 Foxp3 ) and Teff (CD4 Foxp3 ) cell populations, as opposed to significant changes in mice immunized with aSyn and Hsp70 alone. Furthermore, in vitro-stimulated splenocytes from immunized mice showed the lowest relative response against aSyn challenge for the ‘‘aSyn/Hsp70’’ experimental group as measured by IFN-g and IL-17 secretion, and higher IL-10 levels when stimulated with LPS. Finally, serum levels of Th1-cytokine IFN-g and immunomodulatory IL-10 indicated a unique shift toward an immunomodulato-ry/immunoprotective phenotype in mice immunized with the aSyn/Hsp70 complex. Overall, we propose the use of functional ‘‘HSP-chaperoned amyloid/ aggregating proteins’’ generated with appropriate HSP-substrate protein combinations, such as the aSyn/Hsp70 complex, as a novel strategy for immune-based intervention against synucleinopathies and other amyloid or ‘‘misfolding’’ neurodegenerative disorders.Financial support was provided by the Carlos III Institute of Health of Spain (Spanish Ministry of Economy and Competitiveness) according to the Strategic Action in Health (CP10/00527 to CR; PI14-01600 to DP) with co-funding by FEDER funds, the Spanish Ministry of Economy and Competitiveness (SAF-2012/39720 to CR), the Andalusian Ministry of Economy, Science and Innovation (P10-CTS-6928 and P11-CTS-8161 to DP) and the PAIDI Program from the Andalusian Government (CTS- 677 to DP). ALG holds a FPU Predoctoral Fellowship from the Spanish Ministry of Education (AP-2009/3816). The works of EJDG and CMD are supported by the Wellcome Trust, and the UK Medical, and Biotechnological and Biological Sciences Research Councils

Mechanical and electromagnetic design of the vacuum vessel of the SMART tokamak

The SMall Aspect Ratio Tokamak (SMART) is a new spherical device that is currently being designed at the University of Seville. SMART is a compact machine with a plasma major radius (R) greater than 0.4 m, plasma minor radius (a) greater than 0.2 m, an aspect ratio (A) over than 1.7 and an elongation (k) of more than 2. It will be equipped with 4 poloidal field coils, 4 divertor field coils, 12 toroidal field coils and a central solenoid. The heating system comprises of a Neutral Beam Injector (NBI) of 600 kW and an Electron Cyclotron Resonance Heating (ECRH) of 6 kW for pre-ionization. SMART has been designed for a plasma current (I) of 500 kA, a toroidal magnetic field (B) of 1 T and a pulse length of 500 ms preserving the compactness of the machine. The free boundary equilibrium solver code FIESTA [1] coupled to the linear time independent, rigid plasma model RZIP [2] has been used to calculate the target equilibria taking into account the physics goals, the required plasma parameters, vacuum vessel structures and power supply requirements. We present here the final design of the SMART vacuum vessel together with the Finite Element Model (FEM) analysis carried out to ensure that the tokamak vessel provides high quality vacuum and plasma performance withstanding the electromagnetic j×B loads caused by the interaction between the eddy currents induced in the vessel itself and the surrounding magnetic fields. A parametric model has been set up for the topological optimization of the vessel where the thickness of the wall has been locally adapted to the expected forces. An overview of the new machine is presented here.This work received funding from the Fondo Europeo de Desarollo Regional (FEDER) by the European Commission under grant agreement numbers IE17-5670 and US-15570. This work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014-2018 and 2019-2020 under grant agreement No 633053. The views and opinions expressed herein do not necessarily reflect those of the European Commission

Characterization of scintillator screens under irradiation of low energy 133Cs ions

An imaging heavy ion beam probe (i-HIBP) diagnostic, for the simultaneous measurement of plasma density, magnetic field and electrostatic potential in the plasma edge, has been installed at ASDEX Upgrade. Unlike standard heavy ion beam probes, in the i-HIBP the probing (heavy) ions are collected by a scintillator detector, creating a light pattern or strike-line, which is then imaged by a camera. Therefore, a good characterization of the scintillator response is needed. Previous works focused on the scintillator behaviour against irradiation with light ions such as hydrogen and alpha particles. In this work we present the characterization of several scintillator screens - TG-Green (SrGa2S4:Eu2+), YAG-Ce (Y3Al5O12:Ce3+) and P11 (ZnS:Ag) - against irradiation with 133Cs+ ions, in an energy range between 5 and 70 keV and ion currents between 105 and 107 ions/(s·cm2). Three main properties of the scintillators have been studied: the ionolumenescence efficiency or yield, the linearity and the degradation as a function of the fluence. The highest yield was delivered by the TG-Green scintillator screen with > 8·103 photons/ion at 50 keV. All the samples showed a linear response with increasing incident ion flux. The degradation was quantified in terms of the fluence F1/2, which leads to a reduction of the emissivity by a factor of 2. TG-Green showed the lowest degradation with F1/2= 5.4·1014 ions/cm2. After the irradiation the samples were analyzed by Scanning Electron Microscopy (SEM), Rutherford Backscattering Spectrometry (RBS) and Particle Induced X-ray Emission (PIXE). No trace of Cs was found in the irradiated regions. These results indicate that, among the tested materials, TG-Green is the best candidate for the i-HIBP detector.This work received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 805162). G. Birkenmeier acknowledges funding from the Helmholtz Association under grant no. VHNG-1350. J. Galdon-Quiroga acknowledges funding from the Spanish Ministry of Science and Innovation under grant no. FJC2019-041092-I

Impact of COVID-19 pandemic on the PREDIMED-Plus randomized clinical trial: Effects on the interventions, participants follow-up, and adiposity

Background: The COVID-19 pandemic has affected the implementation of most ongoing clinical trials worldwide including the PREDIMED-Plus study. The PREDIMED-Plus is an ongoing, multicenter, controlled intervention trial, aimed at weight-loss and cardiovascular disease prevention, in which participants were randomized (1:1 ratio) to an intervention group (energy-reduced Mediterranean diet, promotion of physical activity, and behavioral support) or to a control group (Mediterranean diet with usual care advice). When the pandemic began, the trial was in the midst of the planned intervention. The objective of this report was to examine the effects of the pandemic on the delivery of the intervention and to describe the strategies established to mitigate the possible adverse effects of the pandemic lockdown on data collection and adiposity. Methods: We assessed the integrity of the PREDIMED-Plus trial during 5 identified periods of the COVID-19 pandemic determined according to restrictions dictated by the Spanish government authorities. A standardized questionnaire was delivered to each of the 23 PREDIMED-Plus recruiting centers to collected data regarding the trial integrity. The effect of the restrictions on intervention components (diet, physical activity) was evaluated with data obtained in the three identified lockdown phases: pre lockdown, lockdown proper, and post lockdown. Results: During the lockdown (March/2020-June/2021), 4,612 participants (48% women, mean age 65y) attended pre-specified yearly follow-up visits to receive lifestyle recommendations and obtain adiposity measures. The overall mean (SD) of the proportions reported by each center showed that 40.4% (25.4) participants had in-person visits, 39.8% (18.2) participants were contacted by telephone and 35% (26.3) by electronic means. Participants' follow-up and data collection rates increased across lockdown periods (from ≈10% at onset to ≈80% at the end). Compared to pre-lockdown, waist circumference increased during (0.75 cm [95% CI: 0.60-0.91]) and after (0.72 cm [95% CI: 0.56-0.89]) lockdown. Body weight did not change during lockdown (0.01 kg [95% CI: -0.10 to 0.13) and decreased after lockdown (-0.17 kg [95% CI: -0.30 to -0.04]). Conclusion: Mitigating strategies to enforce the intervention and patient's follow-up during lockdown have been successful in preserving the integrity of the trial and ensuring its continuation, with minor effects on adiposity. Clinical trial registration: https://doi.org/10.1186/ISRCTN89898870, identifier ISRCTN89898870. Keywords: COVID-19; Mediterraean diet; PREDIMED-Plus; clinical trial; lockdown; weight-loss. Copyright © 2023 Paz-Graniel, Fitó, Ros, Buil-Cosiales, Corella, Babio, Martínez, Alonso-Gómez, Wärnberg, Vioque, Romaguera, López-Miranda, Estruch, Tinahones, Lapetra, Serra-Majem, Bueno-Cavanillas, Tur, Martín-Sánchez, Pintó, Gaforio, Matía-Martín, Vidal, Vázquez, Daimiel, García-Gavilán, Toledo, Nishi, Sorlí, Castañer, García-Ríos, García de la Hera, Barón-López, Ruiz-Canela, Morey, Casas, Garrido-Garrido, Tojal-Sierra, Fernández-García, Vázquez-Ruiz, Fernández-Carrión, Goday, Peña-Orihuela, Compañ-Gabucio, Schröder, Martínez-Gonzalez and Salas-Salvadó. Conflict of interest statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest

Genetic Ancestry, Race, and Severity of Acutely Decompensated Cirrhosis in Latin America

Background & Aims: Genetic ancestry or racial differences in health outcomes exist in diseases associated with systemic inflammation (eg, COVID-19). This study aimed to investigate the association of genetic ancestry and race with acute-on-chronic liver failure (ACLF), which is characterized by acute systemic inflammation, multi-organ failure, and high risk of short-term death. / Methods: This prospective cohort study analyzed a comprehensive set of data, including genetic ancestry and race among several others, in 1274 patients with acutely decompensated cirrhosis who were nonelectively admitted to 44 hospitals from 7 Latin American countries. / Results: Three hundred ninety-five patients (31.0%) had ACLF of any grade at enrollment. Patients with ACLF had a higher median percentage of Native American genetic ancestry and lower median percentage of European ancestry than patients without ACLF (22.6% vs 12.9% and 53.4% vs 59.6%, respectively). The median percentage of African genetic ancestry was low among patients with ACLF and among those without ACLF. In terms of race, a higher percentage of patients with ACLF than patients without ACLF were Native American and a lower percentage of patients with ACLF than patients without ACLF were European American or African American. In multivariable analyses that adjusted for differences in sociodemographic and clinical characteristics, the odds ratio for ACLF at enrollment was 1.08 (95% CI, 1.03–1.13) with Native American genetic ancestry and 2.57 (95% CI, 1.84–3.58) for Native American race vs European American race. / Conclusions: In a large cohort of Latin American patients with acutely decompensated cirrhosis, increasing percentages of Native American ancestry and Native American race were factors independently associated with ACLF at enrollment

Acute Cardiovascular Manifestations in 286 Children With Multisystem Inflammatory Syndrome Associated With COVID-19 Infection in Europe

Background: The aim of the study was to document cardiovascular clinical findings, cardiac imaging, and laboratory markers in children presenting with the novel multisystem inflammatory syndrome associated with coronavirus disease 2019 (COVID-19) infection. Methods: This real-time internet-based survey has been endorsed by the Association for European Paediatric and Congenital Cardiologists Working Groups for Cardiac Imaging and Cardiovascular Intensive Care. Children 0 to 18 years of age admitted to a hospital between February 1 and June 6, 2020, with a diagnosis of an inflammatory syndrome and acute cardiovascular complications were included. Results: A total of 286 children from 55 centers in 17 European countries were included. The median age was 8.4 years (interquartile range, 3.8-12.4 years) and 67% were boys. The most common cardiovascular complications were shock, cardiac arrhythmias, pericardial effusion, and coronary artery dilatation. Reduced left ventricular ejection fraction was present in over half of the patients, and a vast majority of children had raised cardiac troponin when checked. The biochemical markers of inflammation were raised in most patients on admission: elevated C-reactive protein, serum ferritin, procalcitonin, N-terminal pro B-type natriuretic peptide, interleukin-6 level, and D-dimers. There was a statistically significant correlation between degree of elevation in cardiac and biochemical parameters and the need for intensive care support (P<0.05). Polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 was positive in 33.6%, whereas immunoglobulin M and immunoglobulin G antibodies were positive in 15.7% cases and immunoglobulin G in 43.6% cases, respectively, when checked. One child in the study cohort died. Conclusions: Cardiac involvement is common in children with multisystem inflammatory syndrome associated with the Covid-19 pandemic. The majority of children have significantly raised levels of N-terminal pro B-type natriuretic peptide, ferritin, D-dimers, and cardiac troponin in addition to high C-reactive protein and procalcitonin levels. In comparison with adults with COVID-19, mortality in children with multisystem inflammatory syndrome associated with COVID-19 is uncommon despite multisystem involvement, very elevated inflammatory markers, and the need for intensive care support.info:eu-repo/semantics/publishedVersio

Control of somatosensory cortical processing by thalamic posterior medial nucleus: A new role of thalamus in cortical function

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Current knowledge of thalamocortical interaction comes mainly from studying lemniscal thalamic systems. Less is known about paralemniscal thalamic nuclei function. In the vibrissae system, the posterior medial nucleus (POm) is the corresponding paralemniscal nucleus. POm neurons project to L1 and L5A of the primary somatosensory cortex (S1) in the rat brain. It is known that L1 modifies sensory-evoked responses through control of intracortical excitability suggesting that L1 exerts an influence on whisker responses. Therefore, thalamocortical pathways targeting L1 could modulate cortical firing. Here, using a combination of electrophysiology and pharmacology in vivo, we have sought to determine how POm influences cortical processing. In our experiments, single unit recordings performed in urethane- anesthetized rats showed that POm imposes precise control on the magnitude and duration of supra- and infragranular barrel cortex whisker responses. Our findings demonstrated that L1 inputs from POm imposed a time and intensity dependent regulation on cortical sensory processing. Moreover, we found that blocking L1 GABAergic inhibition or blocking P/Q-type Ca2+ channels in L1 prevents POm adjustment of whisker responses in the barrel cortex. Additionally, we found that POm was also controlling the sensory processing in S2 and this regulation was modulated by corticofugal activity from L5 in S1. Taken together, our data demonstrate the determinant role exerted by the POm in the adjustment of somatosensory cortical processing and in the regulation of cortical processing between S1 and S2. We propose that this adjustment could be a thalamocortical gain regulation mechanism also present in the processing of information between cortical areas.This work was supported by a grant from Ministerio de Economia y Competitividad (BFU2012- 36107