63 research outputs found
Cross section of the 197
The 197Au(n,2n)196Au reaction cross section has been measured at two energies, namely at 17.1âMeV and 20.9âMeV, by means of the activation technique, relative to the 27Al(n,α)24Na reference reaction cross section. Quasi-monoenergetic neutron beams were produced at the 5.5âMV Tandem T11/25 accelerator laboratory of NCSR âDemokritosâ, by means of the 3H(d,n)4He reaction, implementing a new Ti-tritiated target ofââŒâ400âGBq activity. The induced Îł-ray activity at the targets and reference foils has been measured with HPGe detectors. The cross section for the population of the second isomeric (12â) state m2 of 196Au was independently determined. Auxiliary Monte Carlo simulations were performed using the MCNP code. The present results are in agreement with previous experimental data and with theoretical calculations of the measured reaction cross sections, which were carried out with the use of the EMPIRE code
COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA)
Background: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods: The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (MarchâMay 2020) and the second wave (OctoberâDecember 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. Conclusions: This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases.EPICOVIDEHA has received funds from Optics COMMITTM (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223)
Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15â20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5â528.7, P = 1.1 Ă 10â4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3â8.2], P = 2.1 Ă 10â4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1â2635.4], P = 3.4 Ă 10â3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3â8.4], P = 7.7 Ă 10â8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 Ă 10â5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old
Decoding the historical tale: COVID-19 impact on haematological malignancy patients-EPICOVIDEHA insights from 2020 to 2022
The COVID-19 pandemic heightened risks for individuals with hematological malignancies due to compromised immune systems, leading to more severe outcomes and increased mortality. While interventions like vaccines, targeted antivirals, and monoclonal antibodies have been effective for the general population, their benefits for these patients may not be as pronounced.Peer reviewe
Cross section of the 197Au(n,2n)196Au reaction
The 197Au(n,2n)196Au reaction cross section has been measured at two energies, namely at 17.1âMeV and 20.9âMeV, by means of the activation technique, relative to the 27Al(n,α)24Na reference reaction cross section. Quasi-monoenergetic neutron beams were produced at the 5.5âMV Tandem T11/25 accelerator laboratory of NCSR âDemokritosâ, by means of the 3H(d,n)4He reaction, implementing a new Ti-tritiated target ofââŒâ400âGBq activity. The induced Îł-ray activity at the targets and reference foils has been measured with HPGe detectors. The cross section for the population of the second isomeric (12â) state m2 of 196Au was independently determined. Auxiliary Monte Carlo simulations were performed using the MCNP code. The present results are in agreement with previous experimental data and with theoretical calculations of the measured reaction cross sections, which were carried out with the use of the EMPIRE code
Cross section of the
The 197Au(n,2n)196Au reaction cross section has been measured at two energies, namely at 17.1âMeV and 20.9âMeV, by means of the activation technique, relative to the 27Al(n,α)24Na reference reaction cross section. Quasi-monoenergetic neutron beams were produced at the 5.5âMV Tandem T11/25 accelerator laboratory of NCSR âDemokritosâ, by means of the 3H(d,n)4He reaction, implementing a new Ti-tritiated target ofââŒâ400âGBq activity. The induced Îł-ray activity at the targets and reference foils has been measured with HPGe detectors. The cross section for the population of the second isomeric (12â) state m2 of 196Au was independently determined. Auxiliary Monte Carlo simulations were performed using the MCNP code. The present results are in agreement with previous experimental data and with theoretical calculations of the measured reaction cross sections, which were carried out with the use of the EMPIRE code
The Hantavirus Surface Glycoprotein Lattice and Its Fusion Control Mechanism
Hantaviruses are rodent-borne viruses causing serious zoonotic outbreaks worldwide for which no treatment is available. Hantavirus particles are pleomorphic and display a characteristic square surface lattice. The envelope glycoproteins Gn and Gc form heterodimers that further assemble into tetrameric spikes, the lattice building blocks. The glycoproteins, which are the sole targets of neutralizing antibodies, drive virus entry via receptor-mediated endocytosis and endosomal membrane fusion. Here we describe the high-resolution X-ray structures of the heterodimer of Gc and the Gn head and of the homotetrameric Gn base. Docking them into an 11.4-angstrom-resolution cryoelectron tomography map of the hantavirus surface accounted for the complete extramembrane portion of the viral glycoprotein shell and allowed a detailed description of the surface organization of these pleomorphic virions. Our results, which further revealed a built-in mechanism controlling Gc membrane insertion for fusion, pave the way for immunogen design to protect against pathogenic hantaviruses.Peer reviewe
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