ClassTR: Classifying Within-Host Heterogeneity Based on Tandem Repeats with Application to Mycobacterium tuberculosis Infections.

Genomic tools have revealed genetically diverse pathogens within some hosts. Within-host pathogen diversity, which we refer to as "complex infection", is increasingly recognized as a determinant of treatment outcome for infections like tuberculosis. Complex infection arises through two mechanisms: within-host mutation (which results in clonal heterogeneity) and reinfection (which results in mixed infections). Estimates of the frequency of within-host mutation and reinfection in populations are critical for understanding the natural history of disease. These estimates influence projections of disease trends and effects of interventions. The genotyping technique MLVA (multiple loci variable-number tandem repeats analysis) can identify complex infections, but the current method to distinguish clonal heterogeneity from mixed infections is based on a rather simple rule. Here we describe ClassTR, a method which leverages MLVA information from isolates collected in a population to distinguish mixed infections from clonal heterogeneity. We formulate the resolution of complex infections into their constituent strains as an optimization problem, and show its NP-completeness. We solve it efficiently by using mixed integer linear programming and graph decomposition. Once the complex infections are resolved into their constituent strains, ClassTR probabilistically classifies isolates as clonally heterogeneous or mixed by using a model of tandem repeat evolution. We first compare ClassTR with the standard rule-based classification on 100 simulated datasets. ClassTR outperforms the standard method, improving classification accuracy from 48% to 80%. We then apply ClassTR to a sample of 436 strains collected from tuberculosis patients in a South African community, of which 92 had complex infections. We find that ClassTR assigns an alternate classification to 18 of the 92 complex infections, suggesting important differences in practice. By explicitly modeling tandem repeat evolution, ClassTR helps to improve our understanding of the mechanisms driving within-host diversity of pathogens like Mycobacterium tuberculosis

Large Magnetic Fields and Motions of OH Masers in W75 N

We report on a second epoch of VLBA observations of the 1665 and 1667 MHz OH masers in the massive star-forming region W75 N. We find evidence to confirm the existence of very strong (~40 mG) magnetic fields near source VLA 2. The masers near VLA 2 are dynamically distinct and include a very bright spot apparently moving at 50 km/s relative to those around VLA 1. This fast-moving spot may be an example of a rare class of OH masers seen in outflows in star-forming regions. Due to the variability of these masers and the rapidity of their motions, tracking these motions will require multiple observations over a significantly shorter time baseline than obtained here. Proper motions of the masers near VLA 1 are more suggestive of streaming along magnetized shocks rather than Keplerian rotation in a disk. The motions of the easternmost cluster of masers in W75 N (B) may be tracing slow expansion around an unseen exciting source.Comment: 7 pages including 4 figures (2 color) & 3 tables, to appear in Ap

Model Independent Tests of Skyrmions and Their Holographic Cousins

We describe a new exact relation for large $N_c$ QCD for the long-distance behavior of baryon form factors in the chiral limit. This model-independent relation is used to test the consistency of the structure of several baryon models. All 4D semiclassical chiral soliton models satisfy the relation, as does the Pomarol-Wulzer holographic model of baryons as 5D Skyrmions. However, remarkably, we find that the holographic model treating baryons as instantons in the Sakai-Sugimoto model does not satisfy the relation.Comment: v2. Added references, corrected typo

Trading off Time, Carbon, Active Travel, and Health: What do People Really Think about Traffic-reduction Measures?

An online survey polled a socio-demographically representative sample of approximately 2,000 UK residents concerning their attitudes to traffic restrictions that lead to longer car trips. Specifically, to what extent would respondents accept delays to everyday local car journeys if these were offset by reductions in NO2, greenhouse gas emissions or vehicular traffic, or by increases in active travel? Responses suggested high levels of acceptance of delay but this varied by nature of impact (less openness to increased active travel) and socio-demographic attribute (gender, educational attainment, car ownership, ethnicity, housing tenure, prior presence of local traffic restrictions). In particular, there were lower levels of delay acceptance amongst men, respondents without degree-level qualifications, and those in households with two or more cars. These findings are relevant to those communicating about traffic restrictions, in terms of which audiences they target and how they present impacts

Hyperfine splitting of the dressed hydrogen atom ground state in non-relativistic QED

We consider a spin-1/2 electron and a spin-1/2 nucleus interacting with the quantized electromagnetic field in the standard model of non-relativistic QED. For a fixed total momentum sufficiently small, we study the multiplicity of the ground state of the reduced Hamiltonian. We prove that the coupling between the spins of the charged particles and the electromagnetic field splits the degeneracy of the ground state.Comment: 22 page