A Bayesian inference framework to reconstruct transmission trees using epidemiological and genetic data

The accurate identification of the route of transmission taken by an infectious agent through a host population is critical to understanding its epidemiology and informing measures for its control. However, reconstruction of transmission routes during an epidemic is often an underdetermined problem: data about the location and timings of infections can be incomplete, inaccurate, and compatible with a large number of different transmission scenarios. For fast-evolving pathogens like RNA viruses, inference can be strengthened by using genetic data, nowadays easily and affordably generated. However, significant statistical challenges remain to be overcome in the full integration of these different data types if transmission trees are to be reliably estimated. We present here a framework leading to a bayesian inference scheme that combines genetic and epidemiological data, able to reconstruct most likely transmission patterns and infection dates. After testing our approach with simulated data, we apply the method to two UK epidemics of Foot-and-Mouth Disease Virus (FMDV): the 2007 outbreak, and a subset of the large 2001 epidemic. In the first case, we are able to confirm the role of a specific premise as the link between the two phases of the epidemics, while transmissions more densely clustered in space and time remain harder to resolve. When we consider data collected from the 2001 epidemic during a time of national emergency, our inference scheme robustly infers transmission chains, and uncovers the presence of undetected premises, thus providing a useful tool for epidemiological studies in real time. The generation of genetic data is becoming routine in epidemiological investigations, but the development of analytical tools maximizing the value of these data remains a priority. Our method, while applied here in the context of FMDV, is general and with slight modification can be used in any situation where both spatiotemporal and genetic data are available

Evolution of foot-and-mouth disease virus intra-sample sequence diversity during serial transmission in bovine hosts

RNA virus populations within samples are highly heterogeneous, containing a large number of minority sequence variants which can potentially be transmitted to other susceptible hosts. Consequently, consensus genome sequences provide an incomplete picture of the within- and between-host viral evolutionary dynamics during transmission. Foot-and-mouth disease virus (FMDV) is an RNA virus that can spread from primary sites of replication, via the systemic circulation, to found distinct sites of local infection at epithelial surfaces. Viral evolution in these different tissues occurs independently, each of them potentially providing a source of virus to seed subsequent transmission events. This study employed the Illumina Genome Analyzer platform to sequence 18 FMDV samples collected from a chain of sequentially infected cattle. These data generated snap-shots of the evolving viral population structures within different animals and tissues. Analyses of the mutation spectra revealed polymorphisms at frequencies >0.5% at between 21 and 146 sites across the genome for these samples, while 13 sites acquired mutations in excess of consensus frequency (50%). Analysis of polymorphism frequency revealed that a number of minority variants were transmitted during host-to-host infection events, while the size of the intra-host founder populations appeared to be smaller. These data indicate that viral population complexity is influenced by small intra-host bottlenecks and relatively large inter-host bottlenecks. The dynamics of minority variants are consistent with the actions of genetic drift rather than strong selection. These results provide novel insights into the evolution of FMDV that can be applied to reconstruct both intra- and inter-host transmission routes

Light Charged Higgs Bosons in Supersymmetric Models

We point out that present experimental limits from searches for neutral Higgs bosons at LEP already imply stringent lower bounds on the mass of the charged Higgs boson in the Minimal Supersymmetric Standard Model (MSSM); these bounds are especially severe for low values of \tanb (\tanb \leq 3), where the $H^+ \bar{t} b$ coupling is large. However, these indirect constraints are much weaker in simple extensions of the MSSM Higgs sector involving the introduction of an extra U(1) gauge group or an extra $SU(2) \times U(1)_Y$ Higgs singlet field; in the latter case charged Higgs bosons can even be light enough to be pair produced at LEP.Comment: LaTeX with equation.sty, 3 PS figures. Version to appear in PLB: Added one paragraph concerning charged Higgs searches at the Tevatro

Future Prospects: Deep Imaging of Galaxy Outskirts using Telescopes Large and Small

The Universe is almost totally unexplored at low surface brightness levels. In spite of great progress in the construction of large telescopes and improvements in the sensitivity of detectors, the limiting surface brightness of imaging observations has remained static for about forty years. Recent technical advances have at last begun to erode the barriers preventing progress. In this Chapter we describe the technical challenges to low surface brightness imaging, describe some solutions, and highlight some relevant observations that have been undertaken recently with both large and small telescopes. Our main focus will be on discoveries made with the Dragonfly Telephoto Array (Dragonfly), which is a new telescope concept designed to probe the Universe down to hitherto unprecedented low surface brightness levels. We conclude by arguing that these discoveries are probably only scratching the surface of interesting phenomena that are observable when the Universe is explored at low surface brightness levels.Comment: 27 pages, 10 figures, Invited review, Book chapter in "Outskirts of Galaxies", Eds. J. H. Knapen, J. C. Lee and A. Gil de Paz, Astrophysics and Space Science Library, Springer, in pres

Evaluation of two lyophilized molecular assays to rapidly detect foot-and-mouth disease virus directly from clinical samples in field settings

Accurate, timely diagnosis is essential for the control, monitoring and eradication of foot‐and‐mouth disease (FMD). Clinical samples from suspect cases are normally tested at reference laboratories. However, transport of samples to these centralized facilities can be a lengthy process that can impose delays on critical decision making. These concerns have motivated work to evaluate simple‐to‐use technologies, including molecular‐based diagnostic platforms, that can be deployed closer to suspect cases of FMD. In this context, FMD virus (FMDV)‐specific reverse transcription loop‐mediated isothermal amplification (RT‐LAMP) and real‐time RT‐PCR (rRT‐PCR) assays, compatible with simple sample preparation methods and in situ visualization, have been developed which share equivalent analytical sensitivity with laboratory‐based rRT‐PCR. However, the lack of robust ‘ready‐to‐use kits’ that utilize stabilized reagents limits the deployment of these tests into field settings. To address this gap, this study describes the performance of lyophilized rRT‐PCR and RT‐LAMP assays to detect FMDV. Both of these assays are compatible with the use of fluorescence to monitor amplification in real‐time, and for the RT‐LAMP assays end point detection could also be achieved using molecular lateral flow devices. Lyophilization of reagents did not adversely affect the performance of the assays. Importantly, when these assays were deployed into challenging laboratory and field settings within East Africa they proved to be reliable in their ability to detect FMDV in a range of clinical samples from acutely infected as well as convalescent cattle. These data support the use of highly sensitive molecular assays into field settings for simple and rapid detection of FMDV

Multiplicativity of completely bounded p-norms implies a new additivity result

We prove additivity of the minimal conditional entropy associated with a quantum channel Phi, represented by a completely positive (CP), trace-preserving map, when the infimum of S(gamma_{12}) - S(gamma_1) is restricted to states of the form gamma_{12} = (I \ot Phi)(| psi >< psi |). We show that this follows from multiplicativity of the completely bounded norm of Phi considered as a map from L_1 -> L_p for L_p spaces defined by the Schatten p-norm on matrices; we also give an independent proof based on entropy inequalities. Several related multiplicativity results are discussed and proved. In particular, we show that both the usual L_1 -> L_p norm of a CP map and the corresponding completely bounded norm are achieved for positive semi-definite matrices. Physical interpretations are considered, and a new proof of strong subadditivity is presented.Comment: Final version for Commun. Math. Physics. Section 5.2 of previous version deleted in view of the results in quant-ph/0601071 Other changes mino

Heating and decoherence suppression using decoupling techniques

We study the application of decoupling techniques to the case of a damped vibrational mode of a chain of trapped ions, which can be used as a quantum bus in linear ion trap quantum computers. We show that vibrational heating could be efficiently suppressed using appropriate ``parity kicks''. We also show that vibrational decoherence can be suppressed by this decoupling procedure, even though this is generally more difficult because the rate at which the parity kicks have to applied increases with the effective bath temperature.Comment: 13 pages, 5 figures. Typos corrected, references adde

'Drowning in here in his bloody sea' : exploring TV cop drama's representations of the impact of stress in modern policing

The Criminal Justice System is a part of society that is both familiar and hidden. It is familiar in that a large part of daily news and television drama is devoted to it (Carrabine, 2008; Jewkes, 2011). It is hidden in the sense that the majority of the population have little, if any, direct contact with the Criminal Justice System, meaning that the media may be a major force in shaping their views on crime and policing (Carrabine, 2008). As Reiner (2000) notes, the debate about the relationship between the media, policing, and crime has been a key feature of wider societal concerns about crime since the establishment of the modern police force. He outlines the recurring themes in post-war debates in this field. For Conservatives there has been an ongoing concern that the media is criminongenic, as it serves to undermine traditional institutions, including the police. From the viewpoint of radical criminology, the impact of the media is two-fold: it exaggerates legitimate concerns about crime and emphasises the bureaucratic and other restrictions under which the police operate (Reiner, 2000). This is seen as undermining due process and legitimatising what can be termed a ‘maverick’ approach to policing. An early example of this can be seen in Clint Eastwood’s Dirty Harry movies (Siegel, 1971) where Harry Callaghan acts as a one-man law enforcement system outside of the formal legal process, a process portrayed as corrupt, inefficient, and concerned with offenders’ rights rather than protecting victims. From a policing perspective, Reiner (2000) argues that film and TV drama creates a simplistic narrative of crime solving that is almost completely divorced from the reality of modern police work, a finding consistent with more recent work by Cummins et al., (2014)