Cross species transmission of Ovine Johne's Disease - Phase 2 cattle.

One thousand seven hundred and seventy four cattle from 12 properties were sampled by ELISA and faecal culture to detect Johne’s Disease. All properties had a known significant history of Johne’s disease in sheep. They were mostly selected from participants in NOJDP Trial 1.1 (a study to examine the effectiveness of an eradication strategy) and had cattle known to be susceptible to JD at the time that their properties were infected with OJD. All gave negative results on serology; only one animal from a herd of 349 gave a single positive faecal culture result, with all follow-up investigations being negative, suggesting passive transfer of the organism. Due to the small size of some of the herds tested, and the fact that no confirmed infected animals or herds were detected, it is not possible to give maximum estimate of the prevalence of OJD in exposed susceptible cattle. However, using information derived from previous investigations and some additional results in the addendum to this project report, it is known that there are at least 6 cattle herds infected with “S” strain, in NSW, at the present time

Magnetic dipole moments in single and coupled split-ring resonators

We examine the role of magnetic dipoles in single and coupled pairs of metallic split-ring resonators by numerically computing their magnitude and examining their relative contributions to the scattering cross section. We demonstrate that magnetic dipoles can strongly influence the scattering cross section along particular directions. It is also found that the magnetic dipole parallel to the incident magnetic field and/or high-order multipoles may play a significant role in the linear response of coupled split-ring resonators.Comment: 7 pages, 3 figures, 1 tabl

Unanticipated improvement in seizure control in drug-resistant epilepsy - real world observations

Objectives: To determine the clinical features and anti-seizure medication (ASM) strategies associated with an unanticipated substantial improvement in seizure control in patients with drug-resistant epilepsy (DRE). Methods: This retrospective analysis of patients attending a tertiary care epilepsy clinic between 2008 and 2017 identified all patients with active DRE (at least 1 seizure per month for 6 months, despite treatment with 2 different ASMs). All treatment interventions were recorded from when DRE was first identified to the end of the study. The primary end points were seizure freedom or meaningful reduction in seizure frequency (greater than 75 %) sustained for at least 12 months after a treatment intervention. Results: Three hundred and twenty-two patients were included in the analysis. Overall, 10 % became seizure free following ASM adjustment and an additional 10 % had a greater than 75 % improvement in seizure control (median follow-up, 4 years). An ASM introduction was ten times more likely than an ASM dose increase to improve seizure control. Combined focal and generalized epilepsy, intellectual disability and prior treatment with more than 5 ASMs were more frequently observed in those with continued pharmacoresistance. ASM responders were more likely to have primary generalized epilepsy. Rational polytherapy (combining ASMs with different mechanisms of action) was almost ubiquitous amongst ASMs responders (95 % taking at least 2 drugs with different mechanistic targets). Of the ASM additions that heralded improved seizure control, 85 % were maintained at submaximal doses. Conclusions: This retrospective analysis of a large number of ‘real-world’ patients provides evidence to persist with ASM trials in DRE. Early rotation of ASMs if a clinical response is not observed at a substantial dose and rational ASM polytherapy may yield better clinical outcomes in patients with DRE, although a prospective study would need to be conducted to validate these findings

Renormalization group theory for finite-size scaling in extreme statistics

We present a renormalization group (RG) approach to explain universal features of extreme statistics, applied here to independent, identically distributed variables. The outlines of the theory have been described in a previous Letter, the main result being that finite-size shape corrections to the limit distribution can be obtained from a linearization of the RG transformation near a fixed point, leading to the computation of stable perturbations as eigenfunctions. Here we show details of the RG theory which exhibit remarkable similarities to the RG known in statistical physics. Besides the fixed points explaining universality, and the least stable eigendirections accounting for convergence rates and shape corrections, the similarities include marginally stable perturbations which turn out to be generic for the Fisher-Tippett-Gumbel class. Distribution functions containing unstable perturbations are also considered. We find that, after a transitory divergence, they return to the universal fixed line at the same or at a different point depending on the type of perturbation.Comment: 15 pages, 8 figures, to appear in Phys. Rev.

Extreme value statistics and return intervals in long-range correlated uniform deviates

We study extremal statistics and return intervals in stationary long-range correlated sequences for which the underlying probability density function is bounded and uniform. The extremal statistics we consider e.g., maximum relative to minimum are such that the reference point from which the maximum is measured is itself a random quantity. We analytically calculate the limiting distributions for independent and identically distributed random variables, and use these as a reference point for correlated cases. The distributions are different from that of the maximum itself i.e., a Weibull distribution, reflecting the fact that the distribution of the reference point either dominates over or convolves with the distribution of the maximum. The functional form of the limiting distributions is unaffected by correlations, although the convergence is slower. We show that our findings can be directly generalized to a wide class of stochastic processes. We also analyze return interval distributions, and compare them to recent conjectures of their functional form

Using airborne LiDAR Survey to explore historic-era archaeological landscapes of Montserrat in the eastern Caribbean

This article describes what appears to be the first archaeological application of airborne LiDAR survey to historic-era landscapes in the Caribbean archipelago, on the island of Montserrat. LiDAR is proving invaluable in extending the reach of traditional pedestrian survey into less favorable areas, such as those covered by dense neotropical forest and by ashfall from the past two decades of active eruptions by the Soufrière Hills volcano, and to sites in localities that are inaccessible on account of volcanic dangers. Emphasis is placed on two aspects of the research: first, the importance of ongoing, real-time interaction between the LiDAR analyst and the archaeological team in the field; and second, the advantages of exploiting the full potential of the three-dimensional LiDAR point cloud data for purposes of the visualization of archaeological sites and features

The Influence of Meteorology on the Spread of Influenza: Survival Analysis of an Equine Influenza (A/H3N8) Outbreak.

This article comes with 'Supporting Information S1. Survival analysis dataset formulation examples and correlations between explanatory variables in Cox regression modelling of factors associated with time to infection in the largest cluster of the 2007 outbreak of equine influenza in Australia. doi:10.1371/journal.pone.0035284.s001The influences of relative humidity and ambient temperature on the transmission of influenza A viruses have recently been established under controlled laboratory conditions. The interplay of meteorological factors during an actual influenza epidemic is less clear, and research into the contribution of wind to epidemic spread is scarce. By applying geostatistics and survival analysis to data from a large outbreak of equine influenza (A/H3N8), we quantified the association between hazard of infection and air temperature, relative humidity, rainfall, and wind velocity, whilst controlling for premises-level covariates. The pattern of disease spread in space and time was described using extraction mapping and instantaneous hazard curves. Meteorological conditions at each premises location were estimated by kriging daily meteorological data and analysed as time-lagged time-varying predictors using generalised Cox regression. Meteorological covariates time-lagged by three days were strongly associated with hazard of influenza infection, corresponding closely with the incubation period of equine influenza. Hazard of equine influenza infection was higher when relative humidity was 30 km hour−1 from the direction of nearby infected premises were associated with increased hazard of infection. Through combining detailed influenza outbreak and meteorological data, we provide empirical evidence for the underlying environmental mechanisms that influenced the local spread of an outbreak of influenza A. Our analysis supports, and extends, the findings of studies into influenza A transmission conducted under laboratory conditions. The relationships described are of direct importance for managing disease risk during influenza outbreaks in horses, and more generally, advance our understanding of the transmission of influenza A viruses under field conditions.jointly funded by the Australian Biosecurity Cooperative Research Centre for Emerging Infectious Diseases and the Rural Industries Research and Development Corporatio

A cautionary tale of pyridoxine toxicity in cystathionine beta‐synthase deficiency detected by two‐tier newborn screening highlights the need for clear pyridoxine dosing guidelines

Classic homocystinuria is due to deficiency of cystathionine beta‐synthase (CBS), a pyridoxine‐dependent enzyme that, depending on the molecular variants, may be co‐factor responsive. Elevated methionine is often used as the primary analyte to detect CBS deficiency (CBSD) on newborn screening (NBS), but is limited by increased detection of other biochemical disorders with less clear clinical significance such as methionine aminotransferase (MAT) I/III heterozygotes. Our state has implemented a two‐tier NBS algorithm for CBSD that successfully reduced the number of MATI/III heterozygotes, yet effectively detected a mild, co‐factor responsive form of CBSD. After initial diagnosis, newborns with CBSD often undergo a pyridoxine challenge with high‐dose pyridoxine to determine responsiveness. Here we describe our NBS‐identified patient with a mild form of pyridoxine responsive CBSD who developed respiratory failure and rhabdomyolysis consistent with pyridoxine toxicity during a pyridoxine challenge. This case highlights the need for weight‐based dosing and duration recommendations for pyridoxine challenge in neonates.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163455/2/ajmga61815.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163455/1/ajmga61815_am.pd

Expression of an Activated Integrin Promotes Long-Distance Sensory Axon Regeneration in the Spinal Cord.

UNLABELLED: After CNS injury, axon regeneration is blocked by an inhibitory environment consisting of the highly upregulated tenascin-C and chondroitin sulfate proteoglycans (CSPGs). Tenascin-C promotes growth of axons if they express a tenascin-binding integrin, particularly α9β1. Additionally, integrins can be inactivated by CSPGs, and this inhibition can be overcome by the presence of a β1-binding integrin activator, kindlin-1. We examined the synergistic effect of α9 integrin and kindlin-1 on sensory axon regeneration in adult rat spinal cord after dorsal root crush and adeno-associated virus transgene expression in dorsal root ganglia. After 12 weeks, axons from C6-C7 dorsal root ganglia regenerated through the tenascin-C-rich dorsal root entry zone into the dorsal column up to C1 level and above (>25 mm axon length) through a normal pathway. Animals also showed anatomical and electrophysiological evidence of reconnection to the dorsal horn and behavioral recovery in mechanical pressure, thermal pain, and ladder-walking tasks. Expression of α9 integrin or kindlin-1 alone promoted much less regeneration and recovery. SIGNIFICANCE STATEMENT: The study demonstrates that long-distance sensory axon regeneration over a normal pathway and with sensory and sensory-motor recovery can be achieved. This was achieved by expressing an integrin that recognizes tenascin-C, one of the components of glial scar tissue, and an integrin activator. This enabled extensive long-distance (>25 mm) regeneration of both myelinated and unmyelinated sensory axons with topographically correct connections in the spinal cord. The extent of growth and recovery we have seen would probably be clinically significant. Restoration of sensation to hands, perineum, and genitalia would be a significant improvement for a spinal cord-injured patient