Inference of Microbial Recombination Rates from Metagenomic Data

Metagenomic sequencing projects from environments dominated by a small number of species produce genome-wide population samples. We present a two-site composite likelihood estimator of the scaled recombination rate, ρ = 2Nec, that operates on metagenomic assemblies in which each sequenced fragment derives from a different individual. This new estimator properly accounts for sequencing error, as quantified by per-base quality scores, and missing data, as inferred from the placement of reads in a metagenomic assembly. We apply our estimator to data from a sludge metagenome project to demonstrate how this method will elucidate the rates of exchange of genetic material in natural microbial populations. Surprisingly, for a fixed amount of sequencing, this estimator has lower variance than similar methods that operate on more traditional population genetic samples of comparable size. In addition, we can infer variation in recombination rate across the genome because metagenomic projects sample genetic diversity genome-wide, not just at particular loci. The method itself makes no assumption specific to microbial populations, opening the door for application to any mixed population sample where the number of individuals sampled is much greater than the number of fragments sequenced

On The Nature of Variations in the Measured Star Formation Efficiency of Molecular Clouds

Measurements of the star formation efficiency (SFE) of giant molecular clouds (GMCs) in the Milky Way generally show a large scatter, which could be intrinsic or observational. We use magnetohydrodynamic simulations of GMCs (including feedback) to forward-model the relationship between the true GMC SFE and observational proxies. We show that individual GMCs trace broad ranges of observed SFE throughout collapse, star formation, and disruption. Low measured SFEs (<<1%) are "real" but correspond to early stages, the true "per-freefall" SFE where most stars actually form can be much larger. Very high (>>10%) values are often artificially enhanced by rapid gas dispersal. Simulations including stellar feedback reproduce observed GMC-scale SFEs, but simulations without feedback produce 20x larger SFEs. Radiative feedback dominates among mechanisms simulated. An anticorrelation of SFE with cloud mass is shown to be an observational artifact. We also explore individual dense "clumps" within GMCs and show that (with feedback) their bulk properties agree well with observations. Predicted SFEs within the dense clumps are ~2x larger than observed, possibly indicating physics other than feedback from massive (main sequence) stars is needed to regulate their collapse.Comment: Fixed typo in the arXiv abstrac

Immune loss as a driver of coexistence during host-phage coevolution

Bacteria and their viral pathogens face constant pressure for augmented immune and infective capabilities, respectively. Under this reciprocally imposed selective regime, we expect to see a runaway evolutionary arms race, ultimately leading to the extinction of one species. Despite this prediction, in many systems host and pathogen coexist with minimal coevolution even when wellmixed. Previous work explained this puzzling phenomenon by invoking fitness tradeoffs, which can diminish an arms race dynamic. Here we propose that the regular loss of immunity by the bacterial host can also produce host-phage coexistence. We pair a general model of immunity with an experimental and theoretical case study of the CRISPR-Cas immune system to contrast the behavior of tradeoff and loss mechanisms in well-mixed systems. We find that, while both mechanisms can produce stable coexistence, only immune loss does so robustly within realistic parameter ranges

Development and evaluation of a patient decision aid for young people and parents considering fixed orthodontic appliances

OBJECTIVES: To develop and evaluate a child-centred patient decision aid for young people, and their parents, supporting shared decision making about fixed orthodontic appliance treatment with dental health professionals, namely the Fixed Appliance Decision Aid (FADA). METHODS: The studies were undertaken in a UK teaching dental hospital orthodontic department in 2013-2014. The development phase involved an interview study with: (a) 10 patients (12-16 years old), and their parents, receiving orthodontic care to investigate treatment decision making and inform the content of the FADA and (b) 23 stakeholders critiquing the draft decision aid's content, structure and utility. The evaluation phase employed a pre-/post-test study design, with 30 patients (12-16 years old) and 30 parents. Outcomes included the Decisional Conflict Scale; measures of orthodontic treatment expectations and knowledge. RESULTS: Qualitative analysis identified two informational needs: effectiveness of treatment on orthodontic outcomes and treatment consequences for patients' lives. Quantitative analysis found decisional conflict reduced in both patients (mean difference -12.3, SD 15.3, 95% CI 6.6-17.9; p < 0.001) and parents (mean difference - 8.6, SD 16.6, 95% CI 2.5-14.8; p = 0.002); knowledge about duration and frequency of orthodontic treatment increased; expectations about care were unchanged. CONCLUSIONS: Using the FADA may enable dental professionals to support patients and their parents, decisions about fixed appliance treatments more effectively, ensuring young people's preferences are integrated into care planning

Uniformly Accelerated Charge in a Quantum Field: From Radiation Reaction to Unruh Effect

We present a stochastic theory for the nonequilibrium dynamics of charges moving in a quantum scalar field based on the worldline influence functional and the close-time-path (CTP or in-in) coarse-grained effective action method. We summarize (1) the steps leading to a derivation of a modified Abraham-Lorentz-Dirac equation whose solutions describe a causal semiclassical theory free of runaway solutions and without pre-acceleration patholigies, and (2) the transformation to a stochastic effective action which generates Abraham-Lorentz-Dirac-Langevin equations depicting the fluctuations of a particle's worldline around its semiclassical trajectory. We point out the misconceptions in trying to directly relate radiation reaction to vacuum fluctuations, and discuss how, in the framework that we have developed, an array of phenomena, from classical radiation and radiation reaction to the Unruh effect, are interrelated to each other as manifestations at the classical, stochastic and quantum levels. Using this method we give a derivation of the Unruh effect for the spacetime worldline coordinates of an accelerating charge. Our stochastic particle-field model, which was inspired by earlier work in cosmological backreaction, can be used as an analog to the black hole backreaction problem describing the stochastic dynamics of a black hole event horizon.Comment: Invited talk given by BLH at the International Assembly on Relativistic Dynamics (IARD), June 2004, Saas Fee, Switzerland. 19 pages, 1 figur

Evaluation of Low versus High Volume per Minute Displacement CO₂ Methods of Euthanasia in the Induction and Duration of Panic-Associated Behavior and Physiology

Current recommendations for the use of CO ₂ as a euthanasia agent for rats require the use of gradual fill protocols (such as 10% to 30% volume displacement per minute) in order to render the animal insensible prior to exposure to levels of CO ₂ that are associated with pain. However, exposing rats to CO ₂ , concentrations as low as 7% CO ₂ are reported to cause distress and 10%-20% CO ₂ induces panic-associated behavior and physiology, but loss of consciousness does not occur until CO ₂ concentrations are at least 40%. This suggests that the use of the currently recommended low flow volume per minute displacement rates create a situation where rats are exposed to concentrations of CO ₂ that induce anxiety, panic, and distress for prolonged periods of time. This study first characterized the response of male rats exposed to normoxic 20% CO ₂ for a prolonged period of time as compared to room air controls. It demonstrated that rats exposed to this experimental condition displayed clinical signs consistent with significantly increased panic-associated behavior and physiology during CO ₂ exposure. When atmospheric air was then again delivered, there was a robust increase in respiration rate that coincided with rats moving to the air intake. The rats exposed to CO ₂ also displayed behaviors consistent with increased anxiety in the behavioral testing that followed the exposure. Next, this study assessed the behavioral and physiologic responses of rats that were euthanized with 100% CO ₂ infused at 10%, 30%, or 100% volume per minute displacement rates. Analysis of the concentrations of CO ₂ and oxygen in the euthanasia chamber and the behavioral responses of the rats suggest that the use of the very low flow volume per minute displacement rate (10%) may prolong the duration of panicogenic ranges of ambient CO ₂ , while the use of the higher flow volume per minute displacement rate (100%) increases agitation. Therefore, of the volume displacement per minute rates evaluated, this study suggests that 30% minimizes the potential pain and distress experienced by the animal

Clusters of Extragalactic Ultra Compact HII Regions

We report on the detection of optically thick free-free radio sources in the galaxies M33, NGC 253, and NGC 6946 using data in the literature. We interpret these sources as being young, embedded star birth regions, which are likely to be clusters of ultracompact HII regions. All 35 of the sources presented in this article have positive radio spectral indices alpha>0 suggesting an optically thick thermal bremsstrahlung emission arising in the HII region surrounding hot stars. Energy requirements indicate a range of a several to >500 O7V star equivalents powering each HII region. Assuming a Salpeter IMF, this corresponds to integrated stellar masses of 0.1--60,000 Msun. For roughly half of the sources in our sample, there is no obvious optical counterpart, giving further support for their deeply embedded nature. Their luminosities and radio spectral energy distributions are consistent with HII regions having electron densities from 1500 cm^-3 to 15000 cm^-3 and radii of 1 - 7 pc. We suggest that the less luminous of these sources are extragalactic ultracompact HII region complexes, those of intermediate luminosity are similar to W49 in the Galaxy, while the brightest will be counterparts to 30 Doradus. These objects constitute the lower mass range of extragalactic ``ultradense HII regions'' which we argue are the youngest stages of massive star cluster formation yet observed. This sample is beginning to fill in the continuum of objects between small associations of ultracompact HII regions and the massive extragalactic clusters that may evolve into globular clusters.Comment: 37 pages, uses AASTeX; scheduled to appear in ApJ v. 559 October 2001. Full postscript version available from http://www.astro.wisc.edu/~chip/Papers/Johnson_Kobulnicky_etal_ApJ559.ps.g

A New Approach to Convective Core Overshooting: Probabilistic Constraints from Color\u2013Magnitude Diagrams of LMC Clusters

We present a framework to simultaneously constrain the values and uncertainties of the strength of convective core overshooting, metallicity, extinction, distance, and age in stellar populations. We then apply the framework to archival Hubble Space Telescope observations of six stellar clusters in the Large Magellanic Cloud that have reported ages between ~1-2.5 Gyr. Assuming a canonical value of the strength of core convective overshooting, we recover the well-known age-metallicity correlation, and additional correlations between metallicity and extinction and metallicity and distance. If we allow the strength of core overshooting to vary, we find that for intermediate-aged stellar clusters, the measured values of distance and extinction are negligibly effected by uncertainties of core overshooting strength. However, cluster age and metallicity may have disconcertingly large systematic shifts when core overshooting strength is allowed to vary by more than +/- 0.05 Hp. Using the six stellar clusters, we combine their posterior distribution functions to obtain the most probable core overshooting value, 0.500 +0.016 -0.134 Hp, which is in line with canonical values. ArXIV