Longitudinal Analysis of Antibody Responses to the mRNA BNT162b2 Vaccine in Patients Undergoing Maintenance Hemodialysis: A 6-Month Follow-Up

Background: Patients on hemodialysis (HD) are at higher risk for COVID-19, overall are poor responders to vaccines, and were prioritized in the Portuguese vaccination campaign.Objective: This work aimed at evaluating in HD patients the immunogenicity of BTN162b2 after the two doses induction phase, the persistence of specific antibodies along time, and factors predicting these outcomes.Methods: We performed a prospective, 6-month long longitudinal cohort analysis of 156 HD patients scheduled to receive BTN162b2. ELISA quantified anti-spike IgG, IgM, and IgA levels in sera were collected every 3 weeks during the induction phase (t0 before vaccine; t1, d21 post first dose; and t2 d21 post second dose), and every 3–4 months during the waning phase (t3, d140, and t4, d180 post first dose). The age-matched control cohort was similarly analyzed from t0 to t2.Results: Upon exclusion of participants identified as previously exposed to SARS-CoV-2, seroconversion at t1 was lower in patients than controls (29 and 50%, respectively, p = 0.0014), while the second vaccine dose served as a boost in both cohorts (91 and 95% positivity, respectively, at t2, p = 0.2463). Lower response in patients than controls at t1 was a singularity of the participants ≤ 70 years (p = 2.01 × 10−05), associated with immunosuppressive therapies (p = 0.013), but not with lack of responsiveness to hepatitis B. Anti-spike IgG, IgM, and IgA levels decreased at t3, with IgG levels further waning at t4 and resulting in >30% seronegativity. Anti-spike IgG levels at t1 and t4 were correlated (ρ = 0.65, p < 2.2 × 10−16).Conclusions: While most HD patients seroconvert upon 2 doses of BNT162b2 vaccination, anti-spike antibodies levels wane over the following 4 months, leading to early seroreversion in a sizeable fraction of the patients. These findings warrant close monitoring of COVID-19 infection in vaccinated HD patients, and advocate for further studies following reinforced vaccination schedules.

Supertagging the Long Tail with Tree-Structured Decoding of Complex Categories

Although current CCG supertaggers achieve high accuracy on the standard WSJ test set, few systems make use of the categories’ internal structure that will drive the syntactic derivation during parsing. The tagset is traditionally truncated, discarding the many rare and complex category types in the long tail. However, supertags are themselves trees. Rather than give up on rare tags, we investigate constructive models that account for their internal structure, including novel methods for tree-structured prediction. Our best tagger is capable of recovering a sizeable fraction of the long-tail supertags and even generates CCG categories that have never been seen in training, while approximating the prior state of the art in overall tag accuracy with fewer parameters. We further investigate how well different approaches generalize to out-of-domain evaluation sets.

Bacteria have numerous distinctive groups of phage–plasmids with conserved phage and variable plasmid gene repertoires

Plasmids and temperate phages are key contributors to bacterial evolution. They are usually regarded as very distinct. However, some elements, termed phage–plasmids, are known to be both plasmids and phages, e.g. P1, N15 or SSU5. The number, distribution, relatedness and characteristics of these phage–plasmids are poorly known. Here, we screened for these elements among ca. 2500 phages and 12000 plasmids and identified 780 phage–plasmids across very diverse bacterial phyla. We grouped 92% of them by similarity of gene repertoires to eight defined groups and 18 other broader communities of elements. The existence of these large groups suggests that phage–plasmids are ancient. Their gene repertoires are large, the average element is larger than an average phage or plasmid, and they include slightly more homologs to phages than to plasmids. We analyzed the pangenomes and the genetic organization of each group of phage–plasmids and found the key phage genes to be conserved and co-localized within distinct groups, whereas genes with homologs in plasmids are much more variable and include most accessory genes. Phage–plasmids are a sizeable fraction of the sequenced plasmids (∼7%) and phages (∼5%), and could have key roles in bridging the genetic divide between phages and other mobile genetic elements.

Computational Analysis of Base Drag Reduction for a Subsonic Missile Projectile at Different Flow Velocity Conditions

Base drag is arising from flow separation at blunt base of a body. It can be a sizeable fraction of total drag in context of projectiles, missiles and after bodies of fighter aircrafts. The base drag is the major contribution of total drag for low speed regimes, flight tests have shown that the base drag may account for up to 50% of total drag. In this paper an experimental investigation for simple semi-circular flight vehicle body of length 500mm and diameter 50mm was conducted for the purpose of investigating base drag. The base drags for three configurations are calculated and the results are compared with CFD data. The three configurations used for testing are flat base configuration, closed nozzle configuration and boat tail configuration. The evaluation of base drag for three different flow velocities such as (i) 20m/s, (ii) 35m/s and (iii) 50m/s at different angle of attack such as -2, 0 and 2 are experimented and compared.

Investigation of Reduction in Base Drag using Experiment and CFD at Subsonic Speed Regimes

Base drag, arising from flow separation at the blunt base of a body can be a sizeable fraction of total drag in the context of projectiles, missiles and after bodies of fighter aircrafts. The base drag is the major contribution of total drag for low speed regimes, flight tests have shown that the base drag may account for up to 50% of the total drag. Computational and experimental investigation for a hemispherical flight vehicle body of length 500mm and diameter 50mm was conducted for the purpose of investigating the base drag. Three case studies were conducted to investigate the properties of the flow field around the flight vehicle at different flow velocities of 20m/s, 30m/s and 50m/s at zero angle of attack (AoA). The three cases were (i) a flight vehicle with flat base configuration, (ii) a flight vehicle with a nozzle at the base and (iii) a flight vehicle configuration with a boat tail, Fig 1. Also, the three configurations were investigated at different AoA of -2, 0 and +2. The base drags for three configurations are calculated and the experimental results are compared with the CFD results.

A protocol for probabilistic extreme event attribution analyses

Over the last few years, methods have been developed to answer questions on the effect of global warming on recent extreme events. Many “event attribution” studies have now been performed, a sizeable fraction even within a few weeks of the event, to increase the usefulness of the results. In doing these analyses, it has become apparent that the attribution itself is only one step of an extended process that leads from the observation of an extreme event to a successfully communicated attribution statement. In this paper we detail the protocol that was developed by the World Weather Attribution group over the course of the last 4 years and about two dozen rapid and slow attribution studies covering warm, cold, wet, dry, and stormy extremes. It starts from the choice of which events to analyse and proceeds with the event definition, observational analysis, model evaluation, multi-model multi-method attribution, hazard synthesis, vulnerability and exposure analysis and ends with the communication procedures. This article documents this protocol. It is hoped that our protocol will be useful in designing future event attribution studies and as a starting point of a protocol for an operational attribution service.

Bacteria have numerous phage-plasmid families with conserved phage and variable plasmid gene repertoires

ABSTRACTPlasmids and temperate phages are mobile genetic elements driving bacterial evolution. They are usually regarded as very distinct. However, some elements, termed phage-plasmids, are known to be both plasmids and phages, e.g. P1, N15 or SSU5. The number, distribution, relatedness and characteristics of these phage-plasmids are poorly known. Here, we screened for these elements among ca. 14000 phages and plasmids and identified 780 phage-plasmids across very diverse bacterial phyla. We grouped 92% of them by similarity of gene repertoires to define 8 families and 18 other broader communities of elements. The existence of these large groups suggests that phage-plasmids are ancient. Their gene repertoires are large, the average element is larger than an average phage or plasmid, and they include slightly more homologs to phages than to plasmids. We analyzed the pangenomes and the genetic organization of each group of phage-plasmids and found the key phage genes to be conserved and co-localized within families, whereas genes with homologs in plasmids are much more variable and include most accessory genes. Phage-plasmids are a sizeable fraction of all phages and plasmids and could have key roles in bridging the genetic divide between phages and other mobile genetic elements.

The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity

SARS-CoV-2 can mutate to evade immunity, with consequences for the efficacy of emerging vaccines and antibody therapeutics. Herein we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is the most divergent region of S, and provide epidemiological, clinical, and molecular characterization of a prevalent RBM variant, N439K. We demonstrate that N439K S protein has enhanced binding affinity to the hACE2 receptor, and that N439K virus has similar clinical outcomes and in vitro replication fitness as compared to wild- type. We observed that the N439K mutation resulted in immune escape from a panel of neutralizing monoclonal antibodies, including one in clinical trials, as well as from polyclonal sera from a sizeable fraction of persons recovered from infection. Immune evasion mutations that maintain virulence and fitness such as N439K can emerge within SARS-CoV-2 S, highlighting the need for ongoing molecular surveillance to guide development and usage of vaccines and therapeutics.

Dark matter simulations with primordial black holes in the early Universe

ABSTRACT Primordial black holes (PBH) with masses of order $10\!-\!30 \, \mathrm{M}_\odot$ have been proposed as a possible explanation of the gravitational waves emission events recently discovered by the Laser Interferometer Gravitational-Wave Observatory (LIGO). If true, then PBHs would constitute a sizeable fraction of the dark matter component in the Universe. Using a series of cosmological N-body simulations that include both dark matter and a variable fraction of PBHs ranging from fPBH = 10−4 to fPBH = 1, we analyse the processes of formation and disruption of gravitationally bound PBH pairs, as well as the merging of both bound and unbound pairs, and estimate the probabilities of such events. We show that they are in good agreement with the constrains to the PBH abundance obtained by the LIGO and other research groups. We find that pair stability, while being a main factor responsible for the merger rate, is significantly affected by the effects of dark matter halo formation and clustering. As a side result, we also evaluate the effects of numerical errors in the stability of bound pairs, which can be useful for future research using this methodology.

The Case for Valuing Non-Health and Indirect Benefits

Health policy is only one part of social policy. Although spending administered by the health sector constitutes a sizeable fraction of total state spending in most countries, other sectors such as education and transportation also represent major portions of national budgets. Additionally, though health is one important aspect of economic and social activity, people pursue many other goals in their social and economic lives. Similarly, direct benefits—those that are immediate results of health policy choices—are only a small portion of the overall impact of health policy. This chapter considers what weight health policy should give to its “spillover effects,” namely non-health and indirect benefits. This chapter defends the view that indirect and non-health benefits should not be given lower priority than direct health benefits in the context of priority-setting in global health.