Densely sampled phylogenies frequently deviate from maximum parsimony in simple and local ways

Why do phylogenetic algorithms fail when they return incorrect answers? This simple question has not been answered in detail, even for maximum parsimony (MP), the simplest phylogenetic criterion. Understanding MP has recently gained relevance in the regime of extremely dense sampling, where each virus sample commonly differs by zero or one mutation from another previously sampled virus. Although recent research shows that evolutionary histories in this regime are close to being maximally parsimonious, the structure of their deviations from MP is not yet understood. In this paper, we develop algorithms to understand how the correct tree deviates from being MP in the densely sampled case. By applying these algorithms to simulations that realistically mimic the evolution of SARS-CoV-2, we find that simulated trees frequently only deviate from maximally parsimonious trees locally, through simple structures consisting of the same mutation appearing independently on sister branches.Comment: 18 pages, 7 figures, submitted to RECOMB 202

The local Gromov-Witten theory of CP^1 and integrable hierarchies

In this paper we begin the study of the relationship between the local Gromov-Witten theory of Calabi-Yau rank two bundles over the projective line and the theory of integrable hierarchies. We first of all construct explicitly, in a large number of cases, the Hamiltonian dispersionless hierarchies that govern the full descendent genus zero theory. Our main tool is the application of Dubrovin's formalism, based on associativity equations, to the known results on the genus zero theory from local mirror symmetry and localization. The hierarchies we find are apparently new, with the exception of the resolved conifold O(-1) + O(-1) -> P1 in the equivariantly Calabi-Yau case. For this example the relevant dispersionless system turns out to be related to the long-wave limit of the Ablowitz-Ladik lattice. This identification provides us with a complete procedure to reconstruct the dispersive hierarchy which should conjecturally be related to the higher genus theory of the resolved conifold. We give a complete proof of this conjecture for genus g<=1; our methods are based on establishing, analogously to the case of KdV, a "quasi-triviality" property for the Ablowitz-Ladik hierarchy at the leading order of the dispersive expansion. We furthermore provide compelling evidence in favour of the resolved conifold/Ablowitz-Ladik correspondence at higher genus by testing it successfully in the primary sector for g=2.Comment: 30 pages; v2: an issue involving constant maps contributions is pointed out in Sec. 3.3-3.4 and is now taken into account in the proofs of Thm 1.3-1.4, whose statements are unchanged. Several typos, formulae, notational inconsistencies have been fixed. v3: typos fixed, minor textual changes, version to appear on Comm. Math. Phy

On the Genus Two Free Energies for Semisimple Frobenius Manifolds

We represent the genus two free energy of an arbitrary semisimple Frobenius manifold as a sum of contributions associated with dual graphs of certain stable algebraic curves of genus two plus the so-called "genus two G-function". Conjecturally the genus two G-function vanishes for a series of important examples of Frobenius manifolds associated with simple singularities as well as for ${\bf P}^1$-orbifolds with positive Euler characteristics. We explain the reasons for such Conjecture and prove it in certain particular cases.Comment: 37 pages, 3 figures, V2: the published versio

Double Ramification Cycles and Integrable Hierarchies

In this paper we present a new construction of a hamiltonian hierarchy associated to a cohomological field theory. We conjecture that in the semisimple case our hierarchy is related to the Dubrovin–Zhang hierarchy by a Miura transformation, and we check it in several examples

Azithromycin resistance in Escherichia coli and Salmonella from food-producing animals and meat in Europe.

OBJECTIVES To characterize the genetic basis of azithromycin resistance in Escherichia coli and Salmonella collected within the EU harmonized antimicrobial resistance (AMR) surveillance programme in 2014-18 and the Danish AMR surveillance programme in 2016-19. METHODS WGS data of 1007 E. coli [165 azithromycin resistant (MIC > 16 mg/L)] and 269 Salmonella [29 azithromycin resistant (MIC > 16 mg/L)] were screened for acquired macrolide resistance genes and mutations in rplDV, 23S rRNA and acrB genes using ResFinder v4.0, AMRFinder Plus and custom scripts. Genotype-phenotype concordance was determined for all isolates. Transferability of mef(C)-mph(G)-carrying plasmids was assessed by conjugation experiments. RESULTS mph(A), mph(B), mef(B), erm(B) and mef(C)-mph(G) were detected in E. coli and Salmonella, whereas erm(C), erm(42), ere(A) and mph(E)-msr(E) were detected in E. coli only. The presence of macrolide resistance genes, alone or in combination, was concordant with the azithromycin-resistant phenotype in 69% of isolates. Distinct mph(A) operon structures were observed in azithromycin-susceptible (n = 50) and -resistant (n = 136) isolates. mef(C)-mph(G) were detected in porcine and bovine E. coli and in porcine Salmonella enterica serovar Derby and Salmonella enterica 1,4, [5],12:i:-, flanked downstream by ISCR2 or TnAs1 and associated with IncIγ and IncFII plasmids. CONCLUSIONS Diverse azithromycin resistance genes were detected in E. coli and Salmonella from food-producing animals and meat in Europe. Azithromycin resistance genes mef(C)-mph(G) and erm(42) appear to be emerging primarily in porcine E. coli isolates. The identification of distinct mph(A) operon structures in susceptible and resistant isolates increases the predictive power of WGS-based methods for in silico detection of azithromycin resistance in Enterobacterales

Structured headache services as the solution to the ill-health burden of headache: 1. Rationale and description

In countries where headache services exist at all, their focus is usually on specialist (tertiary) care. This is clinically and economically inappropriate: most headache disorders can effectively and more efficiently (and at lower cost) be treated in educationally supported primary care. At the same time, compartmentalizing divisions between primary, secondary and tertiary care in many health-care systems create multiple inefficiencies, confronting patients attempting to navigate these levels (the “patient journey”) with perplexing obstacles. High demand for headache care, estimated here in a needs-assessment exercise, is the biggest of the challenges to reform. It is also the principal reason why reform is necessary. The structured headache services model presented here by experts from all world regions on behalf of the Global Campaign against Headache is the suggested health-care solution to headache. It develops and refines previous proposals, responding to the challenge of high demand by basing headache services in primary care, with two supporting arguments. First, only primary care can deliver headache services equitably to the large numbers of people needing it. Second, with educational supports, they can do so effectively to most of these people. The model calls for vertical integration between care levels (primary, secondary and tertiary), and protection of the more advanced levels for the minority of patients who need them. At the same time, it is amenable to horizontal integration with other care services. It is adaptable according to the broader national or regional health services in which headache services should be embedded. It is, according to evidence and argument presented, an efficient and cost-effective model, but these are claims to be tested in formal economic analyses

Transmission in Heteronymous Spinal Pathways Is Modified after Stroke and Related to Motor Incoordination

Changes in reflex spinal pathways after stroke have been shown to affect motor activity in agonist and antagonist muscles acting at the same joint. However, only a few studies have evaluated the heteronymous reflex pathways modulating motoneuronal activity at different joints. This study investigates whether there are changes in the spinal facilitatory and inhibitory pathways linking knee to ankle extensors and if such changes may be related to motor deficits after stroke. The early facilitation and later inhibition of soleus H reflex evoked by the stimulation of femoral nerve at 2 times the motor threshold of the quadriceps were assessed in 15 healthy participants and on the paretic and the non-paretic sides of 15 stroke participants. The relationships between this reflex modulation and the levels of motor recovery, coordination and spasticity were then studied. Results show a significant (Mann-Whitney U; P<0.05) increase in both the peak amplitude (mean±SEM: 80±22% enhancement of the control H reflex) and duration (4.2±0.5 ms) of the facilitation on the paretic side of the stroke individuals compared to their non-paretic side (36±6% and 2.9±0.4 ms) and to the values of the control subjects (33±4% and 2.8±0.4 ms, respectively). Moreover, the later strong inhibition observed in all control subjects was decreased in the stroke subjects. Both the peak amplitude and the duration of the increased facilitation were inversely correlated (Spearman r = −0.65; P = 0.009 and r = −0.67; P = 0.007, respectively) with the level of coordination (LEMOCOT) of the paretic leg. Duration of this facilitation was also correlated (r = −0.58, P = 0.024) with the level of motor recovery (CMSA). These results confirm changes in transmission in heteronymous spinal pathways that are related to motor deficits after stroke

Rifapentine access in Europe: growing concerns over key tuberculosis treatment component

[No abstract available]Support statement: C. Lange is supported by the German Center of Infection Research (DZIF). All other authors have no funding to declare for this study. Funding information for this article has been deposited with the Crossref Funder Registry