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

Association of adipokines and joint biomarkers with cartilage-modifying effects of weight loss in obese subjects

SummaryObjectivesTo determine (1) the effects of weight loss in obese subjects on six adipokines and joint biomarkers; and (2) the relationship between changes in these markers with changes in cartilage outcomes.DesignPlasma levels of adiponectin, leptin, IL-6, COMP, MMP-3 and urine levels of CTX-II were measured at baseline and 12 months from 75 obese subjects enrolled in two weight-loss programs. Magnetic resonance imaging (MRI) was used to assess cartilage volume and thickness. Associations between weight loss, cartilage outcomes and markers were adjusted for age, gender, baseline BMI, presence of clinical knee OA, with and without weight loss percent.ResultsMean weight loss was 13.0 ± 9.5%. Greater weight loss percentage was associated with an increase in adiponectin (β = 0.019, 95% CI 0.012 to 0.026,) and a decrease in leptin (β = −1.09, 95% CI −1.37 to −0.82). Multiple regression analysis saw an increase in adiponectin associated with reduced loss of medial tibial cartilage volume (β = 14.4, CI 2.6 to 26.3) and medial femoral cartilage volume (β = 18.1, 95% CI 4.4 to 31.8). Decrease in leptin was associated with reduced loss of medial femoral volume (β = −4.1, 95% CI −6.8 to −1.4) and lateral femoral volume (β = −1.8, 95% CI −3.7 to 0.0). When weight loss percent was included in the model, only the relationships between COMP and cartilage volume remained statistically significant.ConclusionsAdiponectin and leptin may be associated with cartilage loss. Further work will determine the relative contributions of metabolic and mechanical factors in the obesity-related joint changes

The floor in the interplanetary magnetic field: Estimation on the basis of relative duration of ICME observations in solar wind during 1976-2000

To measure the floor in interplanetary magnetic field and estimate the time- invariant open magnetic flux of Sun, it is necessary to know a part of magnetic field of Sun carried away by CMEs. In contrast with previous papers, we did not use global solar parameters: we identified different large-scale types of solar wind for 1976-2000 interval, obtained a fraction of interplanetary CMEs (ICMEs) and calculated magnitude of interplanetary magnetic field B averaged over 2 Carrington rotations. The floor of magnetic field is estimated as B value at solar cycle minimum when the ICMEs were not observed and it was calculated to be 4,65 \pm 6,0 nT. Obtained value is in a good agreement with previous results.Comment: 10 pages, 2 figures, submitted in GR

Time variation of fundamental couplings and dynamical dark energy

Scalar field dynamics may give rise to a nonzero cosmological variation of fundamental constants. Within different scenarios based on the unification of gauge couplings, the various claimed observations and bounds may be combined in order to trace or restrict the time history of the couplings and masses. If the scalar field is responsible for a dynamical dark energy or quintessence, cosmological information becomes available for its time evolution. Combining this information with the time variation of couplings, one can determine the interaction strength between the scalar and atoms, which may be observed by tests of the Weak Equivalence Principle. We compute bounds on the present rate of coupling variation from experiments testing the differential accelerations for bodies with equal mass and different composition and compare the sensitivity of various methods. In particular, we discuss two specific models of scalar evolution: crossover quintessence and growing neutrino models.Comment: 26 pages, 2 figures; minor typos & added references, to be published in JCA

Ab-initio simulation of high-temperature liquid selenium

Ab initio molecular dynamics simulation is used to investigate the structure and dynamics of liquid Se at temperatures of 870 and 1370~K. The calculated static structure factor is in excellent agreement with experimental data. The calculated radial distribution function gives a mean coordination number close to 2, but we find a significant fraction of one-fold and three-fold atoms, particularly at 1370~K, so that the chain structure is considerably disrupted. The self-diffusion coefficient has values ($\sim 1 \times 10^{-8}$~m~s$^{-1}$) typical of liquid metals.Comment: 10 pages, 4 Poscript figures, uses REVTE

Reconstruction of the trachea with a tubed radial forearm free flap

AbstractBackgroundWe present the case of a patient with adenoid cystic carcinoma of the trachea who had 60 mm of the trachea excised and reconstructed with a stented radial forearm free flap. The patient was well in the immediate postoperative period with good function of the neotrachea. Problems developing after the reconstruction included proximal stricture, sputum retention, and recurrent pneumonia.ResultThe patient died of malignant hypercalcemia 16 months after the reconstruction. To our knowledge this is the first reported case of a total tracheal resection and reconstruction with a combination of free tissue transfer and internal stenting.ConclusionWe conclude that tracheal reconstruction has the potential to provide a reliable airway in patients not able to be reconstructed with a primary anastomosis

Influence of prior walking on postprandial lipaemia in South Asian and White European women

Influence of prior walking on postprandial lipaemia in South Asian and White European wome