Contact transmission of influenza virus between ferrets imposes a looser bottleneck than respiratory droplet transmission allowing propagation of antiviral resistance

Influenza viruses cause annual seasonal epidemics and occasional pandemics. It is important to elucidate the stringency of bottlenecks during transmission to shed light on mechanisms that underlie the evolution and propagation of antigenic drift, host range switching or drug resistance. The virus spreads between people by different routes, including through the air in droplets and aerosols, and by direct contact. By housing ferrets under different conditions, it is possible to mimic various routes of transmission. Here, we inoculated donor animals with a mixture of two viruses whose genomes differed by one or two reverse engineered synonymous mutations, and measured the transmission of the mixture to exposed sentinel animals. Transmission through the air imposed a tight bottleneck since most recipient animals became infected by only one virus. In contrast, a direct contact transmission chain propagated a mixture of viruses suggesting the dose transferred by this route was higher. From animals with a mixed infection of viruses that were resistant and sensitive to the antiviral drug oseltamivir, resistance was propagated through contact transmission but not by air. These data imply that transmission events with a looser bottleneck can propagate minority variants and may be an important route for influenza evolution

How does over-squashing affect the power of GNNs?

Graph Neural Networks (GNNs) are the state-of-the-art model for machine learning on graph-structured data. The most popular class of GNNs operate by exchanging information between adjacent nodes, and are known as Message Passing Neural Networks (MPNNs). Given their widespread use, understanding the expressive power of MPNNs is a key question. However, existing results typically consider settings with uninformative node features. In this paper, we provide a rigorous analysis to determine which function classes of node features can be learned by an MPNN of a given capacity. We do so by measuring the level of pairwise interactions between nodes that MPNNs allow for. This measure provides a novel quantitative characterization of the so-called over-squashing effect, which is observed to occur when a large volume of messages is aggregated into fixed-size vectors. Using our measure, we prove that, to guarantee sufficient communication between pairs of nodes, the capacity of the MPNN must be large enough, depending on properties of the input graph structure, such as commute times. For many relevant scenarios, our analysis results in impossibility statements in practice, showing that over-squashing hinders the expressive power of MPNNs. We validate our theoretical findings through extensive controlled experiments and ablation studies

On diagrammatic bounds of knot volumes and spectral invariants

In recent years, several families of hyperbolic knots have been shown to have both volume and $\lambda_1$ (first eigenvalue of the Laplacian) bounded in terms of the twist number of a diagram, while other families of knots have volume bounded by a generalized twist number. We show that for general knots, neither the twist number nor the generalized twist number of a diagram can provide two-sided bounds on either the volume or $\lambda_1$. We do so by studying the geometry of a family of hyperbolic knots that we call double coil knots, and finding two-sided bounds in terms of the knot diagrams on both the volume and on $\lambda_1$. We also extend a result of Lackenby to show that a collection of double coil knot complements forms an expanding family iff their volume is bounded.Comment: 16 pages, 7 figure

Profinite rigidity for Seifert fibre spaces

An interesting question is whether two 3-manifolds can be distinguished by computing and comparing their collections of finite covers; more precisely, by the profinite completions of their fundamental groups. In this paper, we solve this question completely for closed orientable Seifert fibre spaces. In particular, all Seifert fibre spaces are distinguished from each other by their profinite completions apart from some previously-known examples due to Hempel. We also characterize when bounded Seifert fibre space groups have isomorphic profinite completions, given some conditions on the boundary

Persistent SARS-CoV-2 PCR Positivity Despite Anti-viral Treatment in Immunodeficient Patients

PURPOSE: COVID-19 infection in immunodeficient individuals can result in chronically poor health, persistent or relapsing SARS-CoV-2 PCR positivity, and long-term infectious potential. While clinical trials have demonstrated promising outcomes using anti-SARS-CoV-2 medicines in immunocompetent hosts, their ability to achieve sustained viral clearance in immunodeficient patients remains unknown. We therefore aimed to study long-term virological outcomes in patients treated at our centre. METHODS: We followed up immunocompromised inpatients treated with casirivimab-imdevimab (Ronapreve) between September and December 2021, and immunocompromised patients who received sotrovimab, molnupiravir, nirmatrelvir/ritonavir (Paxlovid), or no treatment from December 2021 to March 2022. Nasopharyngeal swab and sputum samples were obtained either in hospital or in the community until sustained viral clearance, defined as 3 consecutive negative PCR samples, was achieved. Positive samples were sequenced and analysed for mutations of interest. RESULTS: We observed sustained viral clearance in 71 of 103 patients, none of whom died. Of the 32/103 patients where sustained clearance was not confirmed, 6 died (between 2 and 34 days from treatment). Notably, we observed 25 cases of sputum positivity despite negative nasopharyngeal swab samples, as well as recurrence of SARS-CoV-2 positivity following a negative sample in 12 cases. Patients were then divided into those who cleared within 28 days and those with PCR positivity beyond 28 days. We noted lower B cell counts in the group with persistent PCR positivity (mean (SD) 0.06 (0.10) ×109/L vs 0.22 (0.28) ×109/L, p = 0.015) as well as lower IgA (median (IQR) 0.00 (0.00-0.15) g/L vs 0.40 (0.00-0.95) g/L, p = 0.001) and IgM (median (IQR) 0.05 (0.00-0.28) g/L vs 0.35 (0.10-1.10) g/L, p = 0.005). No differences were seen in CD4+ or CD8+ T cell counts. Antiviral treatment did not impact risk of persistent PCR positivity. CONCLUSION: Persistent SARS-CoV-2 PCR positivity is common among immunodeficient individuals, especially those with antibody deficiencies, regardless of anti-viral treatment. Peripheral B cell count and serum IgA and IgM levels are predictors of viral persistence

Expansion in perfect groups

Let Ga be a subgroup of GL_d(Q) generated by a finite symmetric set S. For an integer q, denote by Ga_q the subgroup of Ga consisting of the elements that project to the unit element mod q. We prove that the Cayley graphs of Ga/Ga_q with respect to the generating set S form a family of expanders when q ranges over square-free integers with large prime divisors if and only if the connected component of the Zariski-closure of Ga is perfect.Comment: 62 pages, no figures, revision based on referee's comments: new ideas are explained in more details in the introduction, typos corrected, results and proofs unchange

Quivers, YBE and 3-manifolds

We study 4d superconformal indices for a large class of N=1 superconformal quiver gauge theories realized combinatorially as a bipartite graph or a set of "zig-zag paths" on a two-dimensional torus T^2. An exchange of loops, which we call a "double Yang-Baxter move", gives the Seiberg duality of the gauge theory, and the invariance of the index under the duality is translated into the Yang-Baxter-type equation of a spin system defined on a "Z-invariant" lattice on T^2. When we compactify the gauge theory to 3d, Higgs the theory and then compactify further to 2d, the superconformal index reduces to an integral of quantum/classical dilogarithm functions. The saddle point of this integral unexpectedly reproduces the hyperbolic volume of a hyperbolic 3-manifold. The 3-manifold is obtained by gluing hyperbolic ideal polyhedra in H^3, each of which could be thought of as a 3d lift of the faces of the 2d bipartite graph.The same quantity is also related with the thermodynamic limit of the BPS partition function, or equivalently the genus 0 topological string partition function, on a toric Calabi-Yau manifold dual to quiver gauge theories. We also comment on brane realization of our theories. This paper is a companion to another paper summarizing the results.Comment: 61 pages, 16 figures; v2: typos correcte

Clinical and socioeconomic impact of different types and subtypes of seasonal influenza viruses in children during influenza seasons 2007/2008 and 2008/2009

<p>Abstract</p> <p>Background</p> <p>There are few and debated data regarding possible differences in the clinical presentations of influenza A/H1N1, A/H3N2 and B viruses in children. This study evaluates the clinical presentation and socio-economic impact of laboratory-confirmed influenza A/H1N1, A/H3N2 or B infection in children attending an Emergency Room because of influenza-like illness.</p> <p>Methods</p> <p>Among the 4,726 children involved, 662 had influenza A (143 A/H1N1 and 519 A/H3N2) and 239 influenza B infection detected by means of real-time polymerase chain reaction. Upon enrolment, systematic recordings were made of the patients' demographic characteristics and medical history using standardised written questionnaires. The medical history of the children was re-evaluated 5-7 days after enrolment and until the resolution of their illness by means of interviews and a clinical examination by trained investigators using standardised questionnaires. During this evaluation, information was also obtained regarding illnesses and related morbidity among households.</p> <p>Results</p> <p>Children infected with influenza A/H1N1 were significantly younger (mean age, 2.3 yrs) than children infected with influenza A/H3N2 (mean age, 4.7 yrs; p < 0.05)) or with influenza B (mean age, 5.2 yrs; p < 0.05). Adjusted for age and sex, children with influenza A/H3N2 in comparison with those infected by either A/H1N1 or with B influenza virus were more frequently affected by fever (p < 0.05) and lower respiratory tract involvement (p < 0.05), showed a worse clinical outcome (p < 0.05), required greater drug use (p < 0.05), and suffered a worse socio-economic impact (p < 0.05). Adjusted for age and sex, children with influenza B in comparison with those infected by A/H1N1 influenza virus had significantly higher hospitalization rates (p < 0.05), the households with a disease similar to that of the infected child (p < 0.05) and the need for additional household medical visits (p < 0.05).</p> <p>Conclusions</p> <p>Disease due to influenza A/H3N2 viral subtype is significantly more severe than that due to influenza A/H1N1 subtype and influenza B virus, which indicates that the characteristics of the different viral types and subtypes should be adequately considered by health authorities when planning preventive and therapeutic measures.</p

Discrete element modelling of scaled railway ballast under triaxial conditions

The aim of this study is to demonstrate the use of tetrahedral clumps to model scaled railway ballast using the discrete element method (DEM). In experimental triaxial tests, the peak friction angles for scaled ballast are less sensitive to the confining pressure when compared to full-sized ballast. This is presumed to be due to the size effect on particle strength, whereby smaller particles are statistically stronger and exhibit less abrasion. To investigate this in DEM, the ballast is modelled using clumps with breakable asperities to produce the correct volumetric deformation. The effects of the quantity and properties of these asperities are investigated, and it is shown that the strength affects the macroscopic shear strength at both high and low confining pressures, while the effects of the number of asperities diminishes with increasing confining pressure due to asperity breakage. It is also shown that changing the number of asperities only affects the peak friction angle but not the ultimate friction angle by comparing the angles of repose of samples with different numbers of asperities