Thermal Treatments of AlSi10Mg Processed by Laser Beam Melting

peer reviewedRecent studies have shown that AlSi10Mg processed by Laser Beam Melting (LBM) exhibits a much finer microstructure when compared to its cast counterpart as a consequence of the much faster cooling rates imposed in the LBM process. Such microstructural refinement causes a significant increase in strength and hardness, to such an extent that as-fabricated LBM AlSi10Mg was reported to present hardness value of 127 ± 3 Hv0.5, similar to the hardness of high pressure die cast AlSi10Mg in the aged condition (i.e. 130-133 Hv). Yet, little attention has been given so far to the influence of thermal treatments on the microstructure and mechanical behavior of LBM AlSi10Mg. The present work hence aims to investigate the effect of two different types of heat treatments – i.e. (i) stress relief and (ii) solutionizing and ageing − on the microstructure, hardness and tensile properties of LBM AlSi10Mg

Microstructural and mechanical aspects of AlSi7Mg0.6 alloy related to scanning strategies in L-PBF

AlSi7Mg0.6 alloy is the most widely used cast alloy for aerospace and automotive applications. Therefore, it is essential to explore the effect of scanning strategy parameters on the final part properties in the laser powder bed fusion (L-PBF) process. The effect of stripes and chessboard strategies parameters such as stripe length, rotation angle, and chessboard island size on mechanical and microstructural properties of L-PBF processed AlSi7Mg0.6 alloy is studied. The evolution of the residual stresses is also investigated in the longitudinal and transverse directions. Cooling rates are also estimated using the cell size within the melt pool. Three distinct regions (i.e., fine, coarse, and heat-affected zone) within the melt pool corresponding to different cooling rates could be identified based on Si morphology. The texture of the final material can be tailored by changing the scanning strategies. This study comprehensively presents the results concerning porosity, mechanical properties, crystallographic texture, cooling rates, grain morphology, and residual stresses for additively manufactured AlSi7Mg0.6 alloy

SURFACE ENGINEERING FOR PARTS MADE BY ADDITIVE MANUFACTURING

peer reviewedthe surface preparation of metal parts made by additive manufacturing (AM). AM is a technology of choice for manufacturing of parts with complex shapes (heat exchangers, RF supports, optical parts…) and integrated functions such as conformal cooling channels, clips, hinges, etc. This opens the door for lightweight parts which are of prime importance for space applications. The potential of the AM technologies is however impeded by the quite rough surface finish that is observed on the as-manufactured parts. It is known that such a finish is likely to impact the performance of the parts. Several post-treatment techniques can be applied to improve the surface condition of the AM parts. However, so far, the influence of the successive post-processing steps on the final properties is not well established. Therefore, a better understanding of the impact of surface characteristics on the material behaviour is needed to expand the use of AM for high performance parts. The objective of this study, supported by ESA, is to propose and evaluate various surface finishing techniques for parts made by the AM technologies, in order to check their compatibility, evaluate their properties and derive guidelines for future applications. CRM is the prime proposer of this study and is in charge of the surface treatment and characterisations. Sirris additive manufacturing facilities are used to produce the parts. Thales Alenia Space and Walopt are included into the industrial team to provide concrete application cases. The study focuses on metals. Two metals under study are presented here: AlSi10Mg and Ti6Al4V. This paper is devoted to the early results of the first steps of surface preparation, namely material removal from the surface of the produced parts in order to improve their surface properties. As a first phase, tribo-finishing (TF) is tested on prototype parts to check its capabilities. Surface and volume parameters are analyzed, namely achieved roughness, material removal rate, location of removed material. The limitations in terms of geometry and applicability are discussed as well. These first observations should serve as guidelines for further application of AM for the design of parts used in space industry

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

Enabling planetary science across light-years. Ariel Definition Study Report

Ariel, the Atmospheric Remote-sensing Infrared Exoplanet Large-survey, was adopted as the fourth medium-class mission in ESA's Cosmic Vision programme to be launched in 2029. During its 4-year mission, Ariel will study what exoplanets are made of, how they formed and how they evolve, by surveying a diverse sample of about 1000 extrasolar planets, simultaneously in visible and infrared wavelengths. It is the first mission dedicated to measuring the chemical composition and thermal structures of hundreds of transiting exoplanets, enabling planetary science far beyond the boundaries of the Solar System. The payload consists of an off-axis Cassegrain telescope (primary mirror 1100 mm x 730 mm ellipse) and two separate instruments (FGS and AIRS) covering simultaneously 0.5-7.8 micron spectral range. The satellite is best placed into an L2 orbit to maximise the thermal stability and the field of regard. The payload module is passively cooled via a series of V-Groove radiators; the detectors for the AIRS are the only items that require active cooling via an active Ne JT cooler. The Ariel payload is developed by a consortium of more than 50 institutes from 16 ESA countries, which include the UK, France, Italy, Belgium, Poland, Spain, Austria, Denmark, Ireland, Portugal, Czech Republic, Hungary, the Netherlands, Sweden, Norway, Estonia, and a NASA contribution

Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

Publisher Copyright: © 2021 The Authors, some rights reserved.Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-alpha and/or IFN-omega are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-alpha and/or IFN-omega (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients >80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1124 deceased patients (aged 20 days to 99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-beta. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-alpha and/or IFN-omega are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of individuals carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals 80 years. By contrast, auto-Abs neutralizing IFN-beta do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over 80s and total fatal COVID-19 cases.Peer reviewe

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

SignificanceThere is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged 4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute; The Rockefeller University; the St. Giles Foundation; the NIH (Grants R01AI088364 and R01AI163029); the National Center for Advancing Translational Sciences; NIH Clinical and Translational Science Awards program (Grant UL1 TR001866); a Fast Grant from Emergent Ventures; Mercatus Center at George Mason University; the Yale Center for Mendelian Genomics and the Genome Sequencing Program Coordinating Center funded by the National Human Genome Research Institute (Grants UM1HG006504 and U24HG008956); the Yale High Performance Computing Center (Grant S10OD018521); the Fisher Center for Alzheimer’s Research Foundation; the Meyer Foundation; the JPB Foundation; the French National Research Agency (ANR) under the “Investments for the Future” program (Grant ANR-10-IAHU-01); the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (Grant ANR-10-LABX-62-IBEID); the French Foundation for Medical Research (FRM) (Grant EQU201903007798); the French Agency for Research on AIDS and Viral hepatitis (ANRS) Nord-Sud (Grant ANRS-COV05); the ANR GENVIR (Grant ANR-20-CE93-003), AABIFNCOV (Grant ANR-20-CO11-0001), CNSVIRGEN (Grant ANR-19-CE15-0009-01), and GenMIS-C (Grant ANR-21-COVR-0039) projects; the Square Foundation; Grandir–Fonds de solidarité pour l’Enfance; the Fondation du Souffle; the SCOR Corporate Foundation for Science; The French Ministry of Higher Education, Research, and Innovation (Grant MESRI-COVID-19); Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM; and the University Paris Cité. P. Bastard was supported by the FRM (Award EA20170638020). P. Bastard., J.R., and T.L.V. were supported by the MD-PhD program of the Imagine Institute (with the support of Fondation Bettencourt Schueller). Work at the Neurometabolic Disease lab received funding from Centre for Biomedical Research on Rare Diseases (CIBERER) (Grant ACCI20-767) and the European Union's Horizon 2020 research and innovation program under grant agreement 824110 (EASI Genomics). Work in the Laboratory of Virology and Infectious Disease was supported by the NIH (Grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1), a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. The Infanta Leonor University Hospital supported the research of the Department of Internal Medicine and Allergology. The French COVID Cohort study group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (Grant PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (Grant RECOVER WP 6). This work was also partly supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research, NIH (Grants ZIA AI001270 to L.D.N. and 1ZIAAI001265 to H.C.S.). This program is supported by the Agence Nationale de la Recherche (Grant ANR-10-LABX-69-01). K.K.’s group was supported by the Estonian Research Council, through Grants PRG117 and PRG377. R.H. was supported by an Al Jalila Foundation Seed Grant (Grant AJF202019), Dubai, United Arab Emirates, and a COVID-19 research grant (Grant CoV19-0307) from the University of Sharjah, United Arab Emirates. S.G.T. is supported by Investigator and Program Grants awarded by the National Health and Medical Research Council of Australia and a University of New South Wales COVID Rapid Response Initiative Grant. L.I. reports funding from Regione Lombardia, Italy (project “Risposta immune in pazienti con COVID-19 e co-morbidità”). This research was partially supported by the Instituto de Salud Carlos III (Grant COV20/0968). J.R.H. reports funding from Biomedical Advanced Research and Development Authority (Grant HHSO10201600031C). S.O. reports funding from Research Program on Emerging and Re-emerging Infectious Diseases from Japan Agency for Medical Research and Development (Grant JP20fk0108531). G.G. was supported by the ANR Flash COVID-19 program and SARS-CoV-2 Program of the Faculty of Medicine from Sorbonne University iCOVID programs. The 3C Study was conducted under a partnership agreement between INSERM, Victor Segalen Bordeaux 2 University, and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study was also supported by the Caisse Nationale d’Assurance Maladie des Travailleurs Salariés, Direction générale de la Santé, Mutuelle Générale de l’Education Nationale, Institut de la Longévité, Conseils Régionaux of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research–INSERM Program “Cohortes et collections de données biologiques.” S. Debette was supported by the University of Bordeaux Initiative of Excellence. P.K.G. reports funding from the National Cancer Institute, NIH, under Contract 75N91019D00024, Task Order 75N91021F00001. J.W. is supported by a Research Foundation - Flanders (FWO) Fundamental Clinical Mandate (Grant 1833317N). Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. Work at Vall d’Hebron was also partly supported by research funding from Instituto de Salud Carlos III Grant PI17/00660 cofinanced by the European Regional Development Fund (ERDF/FEDER). C.R.-G. and colleagues from the Canarian Health System Sequencing Hub were supported by the Instituto de Salud Carlos III (Grants COV20_01333 and COV20_01334), the Spanish Ministry for Science and Innovation (RTC-2017-6471-1; AEI/FEDER, European Union), Fundación DISA (Grants OA18/017 and OA20/024), and Cabildo Insular de Tenerife (Grants CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). T.H.M. was supported by grants from the Novo Nordisk Foundation (Grants NNF20OC0064890 and NNF21OC0067157). C.M.B. is supported by a Michael Smith Foundation for Health Research Health Professional-Investigator Award. P.Q.H. and L. Hammarström were funded by the European Union’s Horizon 2020 research and innovation program (Antibody Therapy Against Coronavirus consortium, Grant 101003650). Work at Y.-L.L.’s laboratory in the University of Hong Kong (HKU) was supported by the Society for the Relief of Disabled Children. MBBS/PhD study of D.L. in HKU was supported by the Croucher Foundation. J.L.F. was supported in part by the Evaluation-Orientation de la Coopération Scientifique (ECOS) Nord - Coopération Scientifique France-Colombie (ECOS-Nord/Columbian Administrative department of Science, Technology and Innovation [COLCIENCIAS]/Colombian Ministry of National Education [MEN]/Colombian Institute of Educational Credit and Technical Studies Abroad [ICETEX, Grant 806-2018] and Colciencias Contract 713-2016 [Code 111574455633]). A. Klocperk was, in part, supported by Grants NU20-05-00282 and NV18-05-00162 issued by the Czech Health Research Council and Ministry of Health, Czech Republic. L.P. was funded by Program Project COVID-19 OSR-UniSR and Ministero della Salute (Grant COVID-2020-12371617). I.M. is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies (PID); by the Katholieke Universiteit Leuven C1 Grant C16/18/007; by a Flanders Institute for Biotechnology-Grand Challenges - PID grant; by the FWO Grants G0C8517N, G0B5120N, and G0E8420N; and by the Jeffrey Modell Foundation. I.M. has received funding under the European Union’s Horizon 2020 research and innovation program (Grant Agreement 948959). E.A. received funding from the Hellenic Foundation for Research and Innovation (Grant INTERFLU 1574). M. Vidigal received funding from the São Paulo Research Foundation (Grant 2020/09702-1) and JBS SA (Grant 69004). The NH-COVAIR study group consortium was supported by a grant from the Meath Foundation.Peer reviewe