Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Design and configurations for the Shielding of the Beam Dump of IFMIF DONES

IFMIF-DONES (International Fusion Materials Irradiation Facility–DEMO Oriented Neutron Source) is currentlybeing developed in the frame of the EUROfusion Early Neutron Source work package (WPENS). It will be aninstallation for fusion material testing, that will generate aflux of neutrons of 1018m−2s−1with a broad peak at14 MeV by Li(d,xn) nuclear reactions thanks to a deuteron beam colliding on a liquid Liflow.The accelerator system is in charge of providing such high energy deuterons in order to produce the neutronflux expected. The objective of the Beam Dump, part of the High Energy Beam Transport Line (HEBT), is to stopthe pulsed beam at low duty cycle during DONES accelerator commissioning and start-up phases.The present work explains the radiological design of the beam dump shielding and two different configurationapproaches for the materialization of the design. The radiological design considers maintenance and operation,and it was done together with the building walls dimensioning so that the combined radiation attenuation by thelocal shield and the building leads to dose rates in the different rooms that satisfy the requirements. Activation ofthe materials in the HEBT line, originated by the leakage of neutrons through the beam dump entrance isevaluated and an ad-hoc solution is proposed for its minimization. Regarding the mechanical design, in thefirstconfiguration, the shielding is split into two halves horizontally, the upper-half requiring external lifting cap-abilities for its commission and maintenance. The second approach consists in a vertical splitting into two halves,which are self-moveable, avoiding the needs of external lifting capabilities for the remote handling of theshielding.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 undergrant agreement No 633053. The views and opinions expressed hereindo not necessarily reflect those of the European Commission.The radiological design of the shield has been supported by the Spanish Government in the frame of the Broader Approach Agreement.The work done by IREC has been supported by the CERCA Programme from Generalitat de Catalunya (Government of Catalonia).Peer reviewe

Detailed mechanical design of the LIPAc beam dump radiological shielding

The LIPAc is a 9 MeV, D+ linear prototype accelerator for the validation of the IFMIF accelerator design. The high intensity, 125 mA CW beam is stopped in a copper cone involving a high production of neutrons and gamma radiation and activation of its surface. The beam stopper is surrounded by a shielding to attenuate the resulting radiation so that dose rate values comply with the limits at the different zones of the installation. The shielding includes for that purpose polyethylene rings, water tanks and gray cast iron rings. A lead shutter has also been designed to shield the gamma radiation that comes through the beam tube when the linear accelerator is not in operation, in order to allow access inside the building for maintenance tasks. The present work summarizes the detailed mechanical design of the beam dump shielding and the lead shutter taking into account the design constraints, such as working conditions and other external loads, as well as including provisions for dismantling.Peer Reviewe

Detailed mechanical design of the LIPAc beam dump radiological shielding

The LIPAc is a 9 MeV, D+ linear prototype accelerator for the validation of the IFMIF accelerator design. The high intensity, 125 mA CW beam is stopped in a copper cone involving a high production of neutrons and gamma radiation and activation of its surface. The beam stopper is surrounded by a shielding to attenuate the resulting radiation so that dose rate values comply with the limits at the different zones of the installation. The shielding includes for that purpose polyethylene rings, water tanks and gray cast iron rings. A lead shutter has also been designed to shield the gamma radiation that comes through the beam tube when the linear accelerator is not in operation, in order to allow access inside the building for maintenance tasks. The present work summarizes the detailed mechanical design of the beam dump shielding and the lead shutter taking into account the design constraints, such as working conditions and other external loads, as well as including provisions for dismantling.Peer Reviewe

Comparison of the Fecal Bacteriome of HIV-Positive and HIV-Negative Older Adults

2023 Descuento MDPIHIV infection is considered a scenario of accelerated aging. Previous studies have suggested a link between aging, frailty, and gut dysbiosis, but there is a knowledge gap regarding the HIV population. Our objective was to compare the fecal bacteriome of older people with HIV (PWH) and non-HIV controls, and to assess potential links between gut dysbiosis and frailty. A total of 36 fecal samples (24 from PWH and 12 from non-HIV controls) were submitted to a metataxonomic analysis targeting the V3–V4 hypervariable region of the 16S rRNA gene. High-quality reads were assembled and classified into operational taxonomic units. Alpha diversity, assessed using the Shannon index, was higher in the control group than in the HIV group (p < 0.05). The relative abundance of the genus Blautia was higher in the HIV group (p < 0.001). The presence of Blautia was also higher in PWH with depression (p = 0.004), whereas the opposite was observed for the genus Bifidobacterium (p = 0.004). Our study shows shifts in the composition of the PWH bacteriome when compared to that of healthy controls. To our knowledge, this is the first study suggesting a potential link between depression and gut dysbiosis in the HIV population.Depto. de Nutrición y Ciencia de los AlimentosFac. de VeterinariaTRUEpubDescuento UC

Combined dielectrophoretic and impedance system for on-chip controlled bacteria concentration: Application to Escherichia coli

The present paper reports a bacteria autonomous controlled concentrator prototype with a user-friendly interface for bench-top applications. It is based on a micro-fluidic lab-on-a-chip and its associated custom instrumentation, which consists in a dielectrophoretic actuator, to pre-concentrate the sample, and an impedance analyser, to measure concentrated bacteria levels. The system is composed by a single micro-fluidic chamber with interdigitated electrodes and a instrumentation with custom electronics. The prototype is supported by a real-time platform connected to a remote computer, which automatically controls the system and displays impedance data used to monitor the status of bacteria accumulation on-chip. The system automates the whole concentrating operation. Performance has been studied for controlled volumes of Escherichia coli (E. coli) samples injected into the micro-fluidic chip at constant flow rate of 10 μL/min. A media conductivity correcting protocol has been developed, as the preliminary results showed distortion of the impedance analyser measurement produced by bacterial media conductivity variations through time. With the correcting protocol, the measured impedance values were related to the quantity of bacteria concentrated with a correlation of 0.988 and a coefficient of variation of 3.1%. Feasibility of E. coli on-chip automated concentration, using the miniaturized system, has been demonstrated. Furthermore, the impedance monitoring protocol had been adjusted and optimized, to handle changes in the electrical properties of the bacteria media over time

Lattice Design for 5MeV-125mA CW RFQ Operation in the LIPAc

International audienceThe installation and commissioning of the LIPAc are ongoing under the Broader Approach agreement, which is the prototype accelerator of the IFMIF for proof of princi-ple and design. The deuteron beam will be accelerated by the RFQ linac from 100 keV to 5 MeV during the com-missioning phase-B and by the SRF linac up to 9 MeV during the phase-C. The commissioning phase-B+ will be implemented between phase-B and C to complete the engineering validation of the RFQ linac before installing the SRF linac. The lattice for the deuteron beam of 5 MeV and 125 mA at the commissioning phase-B+ was designed