Horizon 2020 EuPRAXIA design study

The Horizon 2020 Project EuPRAXIA ("European Plasma Research Accelerator with eXcellence In Applications") is preparing a conceptual design report of a highly compact and cost-effective European facility with multi-GeV electron beams using plasma as the acceleration medium. The accelerator facility will be based on a laser and/or a beam driven plasma acceleration approach and will be used for photon science, high-energy physics (HEP) detector tests, and other applications such as compact X-ray sources for medical imaging or material processing. EuPRAXIA started in November 2015 and will deliver the design report in October 2019. EuPRAXIA aims to be included on the ESFRI roadmap in 2020

Status of the Horizon 2020 EuPRAXIA conceptual design study

The Horizon 2020 project EuPRAXIA (European Plasma Research Accelerator with eXcellence In Applications) is producing a conceptual design report for a highly compact and cost-effective European facility with multi-GeV electron beams accelerated using plasmas. EuPRAXIA will be set up as a distributed Open Innovation platform with two construction sites, one with a focus on beam-driven plasma acceleration (PWFA) and another site with a focus on laser-driven plasma acceleration (LWFA). User areas at both sites will provide access to free-electron laser pilot experiments, positron generation and acceleration, compact radiation sources, and test beams for high-energy physics detector development. Support centres in four different countries will complement the pan-European implementation of this infrastructure

Status of the Horizon 2020 EuPRAXIA conceptual design study

The Horizon 2020 project EuPRAXIA (European Plasma Research Accelerator with eXcellence In Applications) is producing a conceptual design report for a highly compact and cost-effective European facility with multi-GeV electron beams accelerated using plasmas. EuPRAXIA will be set up as a distributed Open Innovation platform with two construction sites, one with a focus on beam-driven plasma acceleration (PWFA) and another site with a focus on laser-driven plasma acceleration (LWFA). User areas at both sites will provide access to free-electron laser pilot experiments, positron generation and acceleration, compact radiation sources, and test beams for high-energy physics detector development. Support centres in four different countries will complement the pan-European implementation of this infrastructure

EuPRAXIA - A compact, cost-efficient particle and radiation source

Plasma accelerators present one of the most suitable candidates for the development of more compact particle acceleration technologies, yet they still lag behind radiofrequency (RF)-based devices when it comes to beam quality, control, stability and power efficiency. The Horizon 2020-funded project EuPRAXIA ("European Plasma Research Accelerator with eXcellence In Applications") aims to overcome the first three of these hurdles by developing a conceptual design for a first international user facility based on plasma acceleration. In this paper we report on the main features, simulation studies and potential applications of this future research infrastructure

Erratum to: EuPRAXIA Conceptual Design Report – Eur. Phys. J. Special Topics 229, 3675-4284 (2020), https://doi.org/10.1140/epjst/e2020-000127-8

International audienceThe online version of the original article can be found at http://https://doi.org/10.1140/epjst/e2020-000127-8</A

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

EuPRAXIA - A Compact, Cost-Efficient Particle and Radiation Source

Plasma accelerators present one of the most suitable candidates for the development of more compact particle acceleration technologies, yet they still lag behind radiofrequency (RF)-based devices when it comes to beam quality, control, stability and power efficiency. The Horizon 2020-funded project EuPRAXIA (“European Plasma Research Accelerator with eXcellence In Applications”) aims to overcome the first three of these hurdles by developing a conceptual design for a first international user facility based on plasma acceleration. In this paper we report on the main features, simulation studies and potential applications of this future research infrastructure

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men