Inferring pandemic growth rates from sequence data

Using sequence data to infer population dynamics is playing an increasing role in the analysis of outbreaks. The most common methods in use, based on coalescent inference, have been widely used but not extensively tested against simulated epidemics. Here, we use simulated data to test the ability of both parametric and non-parametric methods for inference of effective population size (coded in the popular BEAST package) to reconstruct epidemic dynamics. We consider a range of simulations centred on scenarios considered plausible for pandemic influenza, but our conclusions are generic for any exponentially growing epidemic. We highlight systematic biases in non-parametric effective population size estimation. The most prominent such bias leads to the false inference of slowing of epidemic spread in the recent past even when the real epidemic is growing exponentially. We suggest some sampling strategies that could reduce (but not eliminate) some of the biases. Parametric methods can correct for these biases if the infected population size is large. We also explore how some poor sampling strategies (e.g. that over-represent epidemiologically linked clusters of cases) could dramatically exacerbate bias in an uncontrolled manner. Finally, we present a simple diagnostic indicator, based on coalescent density and which can easily be applied to reconstructed phylogenies, that identifies time-periods for which effective population size estimates are less likely to be biased. We illustrate this with an application to the 2009 H1N1 pandemic

Extracting the Number of Short Range Correlated Nucleon Pairs from Inclusive Electron Scattering Data

The extraction of the relative abundances of short-range correlated (SRC) nucleon pairs from inclusive electron scattering is studied using the generalized contact formalism (GCF) with several nuclear interaction models. GCF calculations can reproduce the observed scaling of the cross-section ratios for nuclei relative to deuterium at high xB and large Q2, a2 = (σA/A)/(σd/2). In the nonrelativistic instant-form formulation, the calculation is very sensitive to the model parameters and only reproduces the data using parameters that are inconsistent with ab initio many-body calculations. Using a light-cone GCF formulation significantly decreases this sensitivity and improves the agreement with ab initio calculations. The ratio of similar mass isotopes, such as 40Ca and 48Ca, should be sensitive to the nuclear asymmetry dependence of SRCs, but is found to also be sensitive to low-energy nuclear structure. Thus the empirical association of SRC pair abundances with the measured a2 values is only accurate to about 20%. Improving this will require cross-section calculations that reproduce the data while properly accounting for both nuclear structure and relativistic effects

Extracing the number of short-range corerlated nucleon pairs from inclusive electron scattering data

The extraction of the relative abundances of short-range correlated (SRC) nucleon pairs from inclusive electron scattering is studied using the generalized contact formalism (GCF) with several nuclear interaction models. GCF calculations can reproduce the observed scaling of the cross-section ratios for nuclei relative to deuterium at high-$x_B$ and large-$Q^2$, $a_2=(\sigma_A/A)/(\sigma_d/2)$. In the non-relativistic instant-form formulation, the calculation is very sensitive to the model parameters and only reproduces the data using parameters that are inconsistent with ab-initio many-body calculations. Using a light-cone GCF formulation significantly decreases this sensitivity and improves the agreement with ab-initio calculations. The ratio of similar mass isotopes, such as $^{40}$Ca and $^{48}$Ca, should be sensitive to the nuclear asymmetry dependence of SRCs, but is found to also be sensitive to low-energy nuclear structure. Thus the empirical association of SRC pair abundances with the measured $a_2$ values is only accurate to about $20\%$. Improving this will require cross-section calculations that reproduce the data while properly accounting for both nuclear structure and relativistic effects.Comment: Accepted for publication in Phys. Rev. C (Lett). 6 pages, 4 figures, and online supplementary material

Laser Calibration System for Time of Flight Scintillator Arrays

A laser calibration system was developed for monitoring and calibrating time of flight (TOF) scintillating detector arrays. The system includes setups for both small- and large-scale scintillator arrays. Following test-bench characterization, the laser system was recently commissioned in experimental Hall B at the Thomas Jefferson National Accelerator Facility for use on the new Backward Angle Neutron Detector (BAND) scintillator array. The system successfully provided time walk corrections, absolute time calibration, and TOF drift correction for the scintillators in BAND. This showcases the general applicability of the system for use on high-precision TOF detectors.Comment: 11 pages, 11 figure

Generalized Contact Formalism Analysis of the ⁴He(e,e′pN) Reaction

Measurements of short-range correlations in exclusive 4He (e , e ′ p N) reactions are analyzed using the Generalized Contact Formalism (GCF). We consider both instant-form and light-cone formulations with both the AV18 and local N2LO(1.0) nucleon-nucleon (NN) potentials. We find that kinematic distributions, such as the reconstructed pair opening angle, recoil neutron momentum distribution, and pair center of mass motion, as well as the measured missing energy, missing mass distributions, are all well reproduced by GCF calculations. The missing momentum dependence of the measured 4He (e , e ′ p N) /4He (e , e ′ p) cross-section ratios, sensitive to nature of the NN interaction at short-distacnes, are also well reproduced by GCF calculations using either interaction and formulation. This gives credence to the GCF scale-separated factorized description of the short-distance many-body nuclear wave-function

Antibody responses to avian influenza viruses in wild birds broaden with age

For viruses such as avian influenza, immunity within a host population can drive the emergence of new strains by selecting for viruses with novel antigens that avoid immune recognition. The accumulation of acquired immunity with age is hypothesized to affect how influenza viruses emerge and spread in species of different lifespans. Despite its importance for understanding the behaviour of avian influenza viruses, little is known about age-related accumulation of immunity in the virus's primary reservoir, wild birds. To address this, we studied the age structure of immune responses to avian influenza virus in a wild swan population (Cygnus olor), before and after the population experienced an outbreak of highly pathogenic H5N1 avian influenza in 2008. We performed haemagglutination inhibition assays on sampled sera for five avian influenza strains and show that breadth of response accumulates with age. The observed age-related distribution of antibody responses to avian influenza strains may explain the age-dependent mortality observed during the highly pathogenic H5N1 outbreak. Age structures and species lifespan are probably important determinants of viral epidemiology and virulence in birds

Short-Range Correlations and the Nuclear EMC Effect in Deuterium and Helium-3

The EMC effect in deuterium and helium-3 is studied using a convolution formalism that allows isolating the impact of high-momentum nucleons in short-ranged correlated (SRC) pairs. We assume that the modification of the structure function of bound nucleons is given by a universal (i.e. nucleus independent) function of their virtuality, and find that the effect of such modifications is dominated by nucleons in SRC pairs. This SRC-dominance of nucleon modifications is observed despite the fact that the bulk of the nuclear inelastic scattering cross-section comes from interacting with low-momentum nucleons. These findings are found to be robust to model details including nucleon modification function parametrization, free nucleon structure function and treatment of nucleon motion effects. While existing data cannot discriminate between such model details, we present predictions for measured, but not yet published, tritium EMC effect and tagged nucleon structure functions in deuterium that are sensitive to the neutron structure functions and bound nucleon modification functions.Comment: 9 pages, 9 figures, 1 table, and online supplementary material

Assessing the role of live poultry trade in community-structured transmission of avian influenza in China

The live poultry trade is thought to play an important role in the spread and maintenance of highly pathogenic avian influenza A viruses (HP AIVs) in Asia. Despite an abundance of small-scale observational studies, the role of the poultry trade in disseminating AIV over large geographic areas is still unclear, especially for developing countries with complex poultry production systems. Here we combine virus genomes and reconstructed poultry transportation data to measure and compare the spatial spread in China of three key subtypes of AIV: H5N1, H7N9, and H5N6. Although it is difficult to disentangle the contribution of confounding factors, such as bird migration and spatial distance, we find evidence that the dissemination of these subtypes among domestic poultry is geographically continuous and likely associated with the intensity of the live poultry trade in China. Using two independent data sources and network analysis methods, we report a regional-scale community structure in China that might explain the spread of AIV subtypes in the country. The identification of this structure has the potential to inform more targeted strategies for the prevention and control of AIV in China