Use of whole-genome sequencing to identify clusters of Shigella flexneri associated with sexual transmission in men who have sex with men in England: a validation study using linked behavioural data

Since the 1970s, shigellosis has been reported as a sexually transmissible infection, and in recent years, genomic data have revealed the breadth of Shigella spp. transmission among global networks of men who have sex with men (MSM). In 2015, Public Health England (PHE) introduced routine whole-genome sequencing (WGS) of Shigella spp. to identify transmission clusters. However, limited behavioural information for the cases hampers interpretation. We investigated whether WGS can distinguish between clusters representing sexual transmission in MSM and clusters representing community (non-sexual) transmission to inform infection control. WGS data for Shigella flexneri from August 2015 to July 2017 were aggregated into single linkage clusters based on SNP typing using a range of SNP distances (the standard for Shigella surveillance at PHE is 10 SNPs). Clusters were classified as 'adult male', 'household', 'travel-associated' or 'community' using routine demographic data submitted alongside laboratory cultures. From August 2015 to March 2017, PHE contacted those with shigellosis as part of routine public-health follow-up and collected exposure data on a structured questionnaire, which for the first time included questions about sexual identity and behaviour. The questionnaire data were used to determine whether clusters classified as 'adult male' represented likely sexual transmission between men, thereby validating the use of the SNP clustering tool for informing appropriate public-health responses. Overall, 1006 S. flexneri cases were reported, of which 563 clustered with at least one other case (10-SNP threshold). Linked questionnaire data were available for 106 clustered cases, of which 84.0 % belonged to an 'adult male' cluster. At the 10-SNP threshold, 95.1 % [95 % confidence interval (CI) 88.0-98.1%] of MSM belonged to an 'adult male' cluster, while 73.2 % (95 % CI 49.1-87.5%) of non-MSM belonged to a 'community' or 'travel-associated' cluster. At the 25-SNP threshold, all MSM (95 % CI 96.0-100%) belonged to an 'adult male' cluster and 77.8 % (95 % CI 59.2-89.4%) of non-MSM belonged to a 'community' or 'travel-associated' cluster. Within one phylogenetic clade of S. flexneri, 9 clusters were identified (7 'adult male'; 2 'community') using a 10-SNP threshold, while a single 'adult male' cluster was identified using a 25-SNP threshold. Genotypic markers of azithromycin resistance were detected in 84.5 % (294/348) of 'adult male' cases and 20.9 % (9/43) of cases in other clusters (10-SNP threshold), the latter of which contained gay-identifying men who reported recent same-sex sexual contact. Our study suggests that SNP clustering can be used to identify Shigella clusters representing likely sexual transmission in MSM to inform infection control. Defining clusters requires a flexible approach in terms of genetic relatedness to ensure a clear understanding of underlying transmission networks

Internally Electrodynamic Particle Model: Its Experimental Basis and Its Predictions

The internally electrodynamic (IED) particle model was derived based on overall experimental observations, with the IED process itself being built directly on three experimental facts, a) electric charges present with all material particles, b) an accelerated charge generates electromagnetic waves according to Maxwell's equations and Planck energy equation and c) source motion produces Doppler effect. A set of well-known basic particle equations and properties become predictable based on first principles solutions for the IED process; several key solutions achieved are outlined, including the de Broglie phase wave, de Broglie relations, Schr\"odinger equation, mass, Einstein mass-energy relation, Newton's law of gravity, single particle self interference, and electromagnetic radiation and absorption; these equations and properties have long been broadly experimentally validated or demonstrated. A specific solution also predicts the Doebner-Goldin equation which emerges to represent a form of long-sought quantum wave equation including gravity. A critical review of the key experiments is given which suggests that the IED process underlies the basic particle equations and properties not just sufficiently but also necessarily.Comment: Presentation at the 27th Int Colloq on Group Theo Meth in Phys, 200

Ground-state Spectrum of Light-quark Mesons

A confining, Goldstone theorem preserving, separable Ansatz for the ladder kernel of the two-body Bethe-Salpeter equation is constructed from phenomenologically efficacious $u$, $d$ and $s$ dressed-quark propagators. The simplicity of the approach is its merit. It provides a good description of the ground-state isovector-pseudoscalar, vector and axial-vector meson spectrum; facilitates an exploration of the relative importance of various components of the two-body Bethe-Salpeter amplitudes, showing that sub-leading Dirac components are quantitatively important in the isovector-pseudoscalar meson channels; and allows a scrutiny of the domain of applicability of ladder truncation studies. A colour-antitriplet diquark spectrum is obtained. Shortcomings of separable Ans\"atze and the ladder kernel are highlighted.Comment: 30 pages, LaTeX/REVTEX 3.0, no figure

An improved measurement of muon antineutrino disappearance in MINOS

We report an improved measurement of muon anti-neutrino disappearance over a distance of 735km using the MINOS detectors and the Fermilab Main Injector neutrino beam in a muon anti-neutrino enhanced configuration. From a total exposure of 2.95e20 protons on target, of which 42% have not been previously analyzed, we make the most precise measurement of the anti-neutrino "atmospheric" delta-m squared = 2.62 +0.31/-0.28 (stat.) +/- 0.09 (syst.) and constrain the anti-neutrino atmospheric mixing angle >0.75 (90%CL). These values are in agreement with those measured for muon neutrinos, removing the tension reported previously.Comment: 5 pages, 4 figures. In submission to Phys.Rev.Let

Search for the disappearance of muon antineutrinos in the NuMI neutrino beam

We report constraints on antineutrino oscillation parameters that were obtained by using the two MINOS detectors to measure the 7% muon antineutrino component of the NuMI neutrino beam. In the Far Detector, we select 130 events in the charged-current muon antineutrino sample, compared to a prediction of 136.4 ± 11.7(stat)^(+10.2)_(-8.9)(syst) events under the assumption │Δm^2│ = 2.32 X 10^(-3) eV^2, sin^2(2θ) = 1.0

Measurement of the neutrino mass splitting and flavor mixing by MINOS

Measurements of neutrino oscillations using the disappearance of muon neutrinos from the Fermilab NuMI neutrino beam as observed by the two MINOS detectors are reported. New analysis methods have been applied to an enlarged data sample from an exposure of $7.25 imes 10^{20}$ protons on target. A fit to neutrino oscillations yields values of $|Delta m^2| = (2.32^{+0.12}_{-0.08}) imes10^{-3}$,eV$^2$ for the atmospheric mass splitting and m sin^2!(2 heta) > 0.90 (90%,C.L.) for the mixing angle. Pure neutrino decay and quantum decoherence hypotheses are excluded at 7 and 9 standard deviations, respectively

Measurement of the Neutrino Mass Splitting and Flavor Mixing by MINOS

Measurements of neutrino oscillations using the disappearance of muon neutrinos from the Fermilab NuMI neutrino beam as observed by the two MINOS detectors are reported. New analysis methods have been applied to an enlarged data sample from an exposure of 7.25×10^(20) protons on target. A fit to neutrino oscillations yields values of |Δm^2|=(2.32_(-0.08)^(+0.12))×10^(-3)  eV^2 for the atmospheric mass splitting and sin^2(2θ)>0.90 (90% C.L.) for the mixing angle. Pure neutrino decay and quantum decoherence hypotheses are excluded at 7 and 9 standard deviations, respectively