Age-dependent patterns of bovine tuberculosis in cattle.

Bovine tuberculosis (BTB) is an important livestock disease, seriously impacting cattle industries in both industrialised and pre-industrialised countries. Like TB in other mammals, infection is life long and, if undiagnosed, may progress to disease years after exposure. The risk of disease in humans is highly age-dependent, however in cattle, age-dependent risks have yet to be quantified, largely due to insufficient data and limited diagnostics. Here, we estimate age-specific reactor rates in Great Britain by combining herd-level testing data with spatial movement data from the Cattle Tracing System (CTS). Using a catalytic model, we find strong age dependencies in infection risk and that the probability of detecting infection increases with age. Between 2004 and 2009, infection incidence in cattle fluctuated around 1%. Age-specific incidence increased monotonically until 24-36 months, with cattle aged between 12 and 36 months experiencing the highest rates of infection. Beef and dairy cattle under 24 months experienced similar infection risks, however major differences occurred in older ages. The average reproductive number in cattle was greater than 1 for the years 2004-2009. These methods reveal a consistent pattern of BTB rates with age, across different population structures and testing patterns. The results provide practical insights into BTB epidemiology and control, suggesting that targeting a mass control programme at cattle between 12 and 36 months could be beneficial.EBP is funded by an Engineering and Physical Sciences Research Council (EPSRC) fellowship. JLNW is supported by the Alborada Trust and the RAPIDD program of the Science & Technology Directorate, U.S. Department of Homeland Security, and the Fogarty International Center, U.S. National Institutes of Health. AJKC is supported by Defra grant no. SE-3127. TJM is supported by the BBSRC. We thank Steve Holdship and Rose Nicholson at Defra the AHVLA team for providing access to the CTS and VetNet

Potential Benefits of Cattle Vaccination as a Supplementary Control for Bovine Tuberculosis

This is the final published version of the article. It was originally published in PLOS Computational Biology (Conlan AJK, Brooks Pollock E, McKinley TJ, Mitchell AP, Jones GJ, Vordermeier M, Wood JLN, PLoS Computational Biology 2015, 11(2): e1004038. doi:10.1371/journal.pcbi.1004038).\ud \ud ? 2015 Crown Copyright. This is an open-access article distributed under the terms of the free Open Government Licence, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited. See: http://www.nationalarchives.gov.uk/doc/o?pen-government-licence/open-government-l?icence.htmVaccination for the control of bovine tuberculosis (bTB) in cattle is not currently used within any international control program, and is illegal within the EU. Candidate vaccines, based upon Mycobacterium bovis bacillus Calmette-Gu?rin (BCG) all interfere with the action of the tuberculin skin test, which is used to determine if animals, herds and countries are officially bTB-free. New diagnostic tests that Differentiate Infected from Vaccinated Animals (DIVA) offer the potential to introduce vaccination within existing eradication programs. We use within-herd transmission models estimated from historical data from Great Britain (GB) to explore the feasibility of such supplemental use of vaccination. The economic impact of bovine Tuberculosis for farmers is dominated by the costs associated with testing, and associated restrictions on animal movements. Farmers? willingness to adopt vaccination will require vaccination to not only reduce the burden of infection, but also the risk of restrictions being imposed. We find that, under the intensive sequence of testing in GB, it is the specificity of the DIVA test, rather than the sensitivity, that is the greatest barrier to see a herd level benefit of vaccination. The potential negative effects of vaccination could be mitigated through relaxation of testing. However, this could potentially increase the hidden burden of infection within Officially TB Free herds. Using our models, we explore the range of the DIVA test characteristics necessary to see a protective herd level benefit of vaccination. We estimate that a DIVA specificity of at least 99.85% and sensitivity of >40% is required to see a protective benefit of vaccination with no increase in the risk of missed infection. Data from experimentally infected animals suggest that this target specificity could be achieved in vaccinates using a cocktail of three DIVA antigens while maintaining a sensitivity of 73.3% (95%CI: 61.9, 82.9%) relative to post-mortem detection.This study was funded by Defra project SE3127 and uses nationally collected incidence and cattle-movement data sets held by Defra. The funders had no role in study design, data analysis, decision to publish, or preparation of the manuscript

Potential benefits of cattle vaccination as a supplementary control for bovine tuberculosis

Published onlineJournal ArticleResearch Support, Non-U.S. Gov'tVaccination for the control of bovine tuberculosis (bTB) in cattle is not currently used within any international control program, and is illegal within the EU. Candidate vaccines, based upon Mycobacterium bovis bacillus Calmette-Guérin (BCG) all interfere with the action of the tuberculin skin test, which is used to determine if animals, herds and countries are officially bTB-free. New diagnostic tests that Differentiate Infected from Vaccinated Animals (DIVA) offer the potential to introduce vaccination within existing eradication programs. We use within-herd transmission models estimated from historical data from Great Britain (GB) to explore the feasibility of such supplemental use of vaccination. The economic impact of bovine Tuberculosis for farmers is dominated by the costs associated with testing, and associated restrictions on animal movements. Farmers' willingness to adopt vaccination will require vaccination to not only reduce the burden of infection, but also the risk of restrictions being imposed. We find that, under the intensive sequence of testing in GB, it is the specificity of the DIVA test, rather than the sensitivity, that is the greatest barrier to see a herd level benefit of vaccination. The potential negative effects of vaccination could be mitigated through relaxation of testing. However, this could potentially increase the hidden burden of infection within Officially TB Free herds. Using our models, we explore the range of the DIVA test characteristics necessary to see a protective herd level benefit of vaccination. We estimate that a DIVA specificity of at least 99.85% and sensitivity of >40% is required to see a protective benefit of vaccination with no increase in the risk of missed infection. Data from experimentally infected animals suggest that this target specificity could be achieved in vaccinates using a cocktail of three DIVA antigens while maintaining a sensitivity of 73.3% (95%CI: 61.9, 82.9%) relative to post-mortem detection.This study was funded by Defra project SE3127 and uses nationally collected incidence and cattle-movement data sets held by Defra

Primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphomas: reappraisal of a provisional entity in the 2016 WHO classification of cutaneous lymphomas.

Primary cutaneous CD8-positive aggressive epidermotropic T-cell lymphoma is a rare and poorly characterized variant of cutaneous lymphoma still considered a provisional entity in the latest 2016 World Health Organization Classification of Cutaneous lymphomas. We sought to better characterize and provide diagnostic and therapeutic guidance of this rare cutaneous lymphoma. Thirty-four patients with a median age of 77 years (range 19-89 years) presented primarily with extensive annular necrotic plaques or tumor lesions with frequent mucous membrane involvement. The 5-year survival was 32% with a median survival of 12 months. A subset of 17 patients had a prodrome of chronic patches prior to the development of aggressive ulcerative lesions. We identified cases with lack of CD8 or αβ T-cell receptor expression yet with similar clinical and pathological presentation. Allogeneic stem cell transplantation provided partial or complete remissions in 5/6 patients. We recommend the term primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphoma as this more broad designation better describes this clinical-pathologic presentation, which allows the inclusion of cases with CD8 negative and/or αβ/γδ T-cell receptor chain double-positive or double-negative expression. We have identified early skin signs of chronic patch/plaque lesions that are often misdiagnosed as eczema, psoriasis, or mycosis fungoides. Our experience confirms the poor prognosis of this entity and highlights the inefficacy of our standard therapies with the exception of allogeneic stem cell transplantation in selected cases

Dietary exposures and allergy prevention in high-risk infants

Allergic conditions in children are a prevalent health concern in Canada. The burden of disease and the societal costs of proper diagnosis and management are considerable, making the primary prevention of allergic conditions a desirable health care objective. This position statement reviews current evidence on dietary exposures and allergy prevention in infants at high risk for developing allergic conditions. It revisits previous dietary recommendations for pregnancy, breastfeeding and formula feeding, and provides an approach for introducing solid foods to high-risk infants. While there is no evidence that delaying the introduction of any specific food beyond six months of age helps to prevent allergy, the protective effect of early introduction of potentially allergenic foods (at four to six months of age) remains under investigation. Recent research appears to suggest that regularly ingesting a new, potentially allergenic food may be as important as when that food is first introduced. © Canadian Paediatric Society 2013

Bayesian model comparison with un-normalised likelihoods

Models for which the likelihood function can be evaluated only up to a parameter-dependent unknown normalizing constant, such as Markov random field models, are used widely in computer science, statistical physics, spatial statistics, and network analysis. However, Bayesian analysis of these models using standard Monte Carlo methods is not possible due to the intractability of their likelihood functions. Several methods that permit exact, or close to exact, simulation from the posterior distribution have recently been developed. However, estimating the evidence and Bayes’ factors for these models remains challenging in general. This paper describes new random weight importance sampling and sequential Monte Carlo methods for estimating BFs that use simulation to circumvent the evaluation of the intractable likelihood, and compares them to existing methods. In some cases we observe an advantage in the use of biased weight estimates. An initial investigation into the theoretical and empirical properties of this class of methods is presented. Some support for the use of biased estimates is presented, but we advocate caution in the use of such estimates

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Paternal mtDNA and Maleness Are Co-Inherited but Not Causally Linked in Mytilid Mussels

BACKGROUND: In marine mussels of the genus Mytilus there are two mitochondrial genomes. One is transmitted through the female parent, which is the normal transmission route in animals, and the other is transmitted through the male parent which is an unusual phenomenon. In males the germ cell line is dominated by the paternal mitochondrial genome and the somatic cell line by the maternal. Research to date has not allowed a clear answer to the question of whether inheritance of the paternal genome is causally related to maleness. METHODOLOGY/PRINCIPAL FINDINGS: Here we present results from hybrid crosses, from triploid mussels and from observations of sperm mitochondria in fertilized eggs which clearly show that maleness and presence of the paternal mitochondrial genome can be decoupled. These same results show that the female mussel has exclusive control of whether her progeny will inherit the mitochondrial genome of the male parent. CONCLUSIONS/SIGNIFICANCE: These findings are important in our efforts to understand the mechanistic basis of this unusual mode of mitochondrial DNA inheritance that is common among bivalves