Study of Healthcare Personnel with Influenza and other Respiratory Viruses in Israel (SHIRI): study protocol

Abstract Background The Study of Healthcare Personnel with Influenza and other Respiratory Viruses in Israel (SHIRI) prospectively follows a cohort of healthcare personnel (HCP) in two hospitals in Israel. SHIRI will describe the frequency of influenza virus infections among HCP, identify predictors of vaccine acceptance, examine how repeated influenza vaccination may modify immunogenicity, and evaluate influenza vaccine effectiveness in preventing influenza illness and missed work. Methods Cohort enrollment began in October, 2016; a second year of the study and a second wave of cohort enrollment began in June 2017. The study will run for at least 3 years and will follow approximately 2000 HCP (who are both employees and members of Clalit Health Services [CHS]) with routine direct patient contact. Eligible HCP are recruited using a stratified sampling strategy. After informed consent, participants complete a brief enrollment survey with questions about occupational responsibilities and knowledge, attitudes, and practices about influenza vaccines. Blood samples are collected at enrollment and at the end of influenza season; HCP who choose to be vaccinated contribute additional blood one month after vaccination. During the influenza season, participants receive twice-weekly short message service (SMS) messages asking them if they have acute respiratory illness or febrile illness (ARFI) symptoms. Ill participants receive follow-up SMS messages to confirm illness symptoms and duration and are asked to self-collect a nasal swab. Information on socio-economic characteristics, current and past medical conditions, medical care utilization and vaccination history is extracted from the CHS database. Information about missed work due to illness is obtained by self-report and from employee records. Respiratory specimens from self-collected nasal swabs are tested for influenza A and B viruses, respiratory syncytial virus, human metapneumovirus, and coronaviruses using validated multiplex quantitative real-time reverse transcription polymerase chain reaction assays. The hemagglutination inhibition assay will be used to detect the presence of neutralizing influenza antibodies in serum. Discussion SHIRI will expand our knowledge of the burden of respiratory viral infections among HCP and the effectiveness of current and repeated annual influenza vaccination in preventing influenza illness, medical utilization, and missed workdays among HCP who are in direct contact with patients. Trial registration NCT03331991 . Registered on November 6, 2017.https://deepblue.lib.umich.edu/bitstream/2027.42/146186/1/12879_2018_Article_3444.pd

Improved BGP Convergence via Ghost Flushing

In [1], [2] it was noticed that sometimes it takes BGP a substantial amount of time and messages to converge and stabilize following the failure of some node in the Internet. In this paper we suggest a minor modification to BGP that eliminates the problem pointed out and substantially reduces the convergence time and communication complexity of BGP. Roughly speaking, our modification ensures that bad news (the failure of a node/edge) propagate fast, while good news (the establishment of a new path to a destination) propagate somewhat slower. This is achieved in BGP by allowing withdrawal messages to propagate with no delay as fast as the network forwards them, while announcements propagate as they do in BGP with a delay at each node of one minRouteAd er (except for the first wave of announcements)

High capacity clinical SARS-CoV-2 molecular testing using combinatorial pooling

Abstract Background The SARS-CoV-2 pandemic led to unprecedented testing demands, causing major testing delays globally. One strategy used for increasing testing capacity was pooled-testing, using a two-stage technique first introduced during WWII. However, such traditional pooled testing was used in practice only when positivity rates were below 2%. Methods Here we report the development, validation and clinical application of P-BEST - a single-stage pooled-testing strategy that was approved for clinical use in Israel. Results P-BEST is clinically validated using 3636 side-by-side tests and is able to correctly detect all positive samples and accurately estimate their Ct value. Following regulatory approval by the Israeli Ministry of Health, P-BEST was used in 2021 to clinically test 837,138 samples using 270,095 PCR tests - a 3.1fold reduction in the number of tests. This period includes the Alpha and Delta waves, when positivity rates exceeded 10%, rendering traditional pooling non-practical. We also describe a tablet-based solution that allows performing manual single-stage pooling in settings where liquid dispensing robots are not available. Conclusions Our data provides a proof-of-concept for large-scale clinical implementation of single-stage pooled-testing for continuous surveillance of multiple pathogens with reduced test costs, and as an important tool for increasing testing efficiency during pandemic outbreaks

Engrafted parenchymal brain macrophages differ from microglia in transcriptome, chromatin landscape and response to challenge

Irradiation depletes brain microglia cells and induces replenishment of the pool by bone marrow (BM)-derived macrophage. Here the authors show, using mouse BM chimera, that BM-derived macrophages establish long-term residency in the brain, but remain distinct from resident microglia in their transcriptome and gene accessibility landscape

G1 is the major APOL1 risk allele for hypertension-attributed nephropathy in Central Africa.

peer reviewedBackground: Sub-Saharan Africans exhibit a higher frequency of chronic kidney disease (CKD) than other populations. In this study, we sought to determine the frequency of apolipoprotein L1 (APOL1) genotypes in hypertension-attributed CKD in Kinshasa, Democratic Republic of the Congo. Methods: We performed a case-control study identifying 162 subjects: 79 with hypertension-attributed CKD and 83 controls living in Kinshasa who were genotyped for APOL1 risk variants between July 2013 and November 2016. We selected control subjects from the general population and matched them with the cases according to age. Logistic regression analysis was used to examine the relationship between APOL1 high-risk genotypes and CKD. Results: The frequencies of the APOL1 G1 and G2 alleles were 19.1 and 7.1%, respectively. The number of individuals with the G1 and G2 risk alleles was significantly higher in the CKD group (12.7%) than in the control group (2.4%), particularly in individuals with end-stage kidney disease (14.3%). Subjects carrying two risk alleles was strongly and independently associated with hypertension-attributed nephropathy, with an adjusted odds ratio of 7.7 (95% confidence interval 1.5-39.7; P = 0.014). The high-risk APOL1 genotypes were G1/G1 and G1/G2, whereas G2/G2 was not found in the study population. Conclusions: The results of this study demonstrate the association of high-risk APOL1 genotypes with kidney disease in Kinshasa. The absence of G2/G2 may be consistent with powerful selective sweeps induced by Trypanosoma brucei gambiense infection. In contrast, the presence of APOL1 G2/G2 among individuals of African ancestry in the USA may indicate relaxation of natural selection in a trypanosome-free environment

Guidelines for the use of flow cytometry and cell sorting in immunological studies

International audienceThe classical model of hematopoiesis established in the mouse postulates that lymphoid cells originate from a founder population of common lymphoid progenitors. Here, using a modeling approach in humanized mice, we showed that human lymphoid development stemmed from distinct populations of CD127(-) and CD127(+) early lymphoid progenitors (ELPs). Combining molecular analyses with in vitro and in vivo functional assays, we demonstrated that CD127(-) and CD127(+) ELPs emerged independently from lympho-mono-dendritic progenitors, responded differently to Notch1 signals, underwent divergent modes of lineage restriction, and displayed both common and specific differentiation potentials. Whereas CD127(-) ELPs comprised precursors of T cells, marginal zone B cells, and natural killer (NK) and innate lymphoid cells (ILCs), CD127(+) ELPs supported production of all NK cell, ILC, and B cell populations but lacked T potential. On the basis of these results, we propose a "two-family" model of human lymphoid development that differs from the prevailing model of hematopoiesis