THE DESIGN AND ANALYSIS OF EXPERIMENTS. By Oscar Kempthorne. New York, John Wiley and Sons, Inc., 1952. 631 pp. $8.50. This book by a teacher of statistics (as well as a consultant for \"experimenters\") is a comprehensive study of the philosophical background for the statistical design of experiment. It is necessary to have some facility with algebraic notation and manipulation to be able to use the volume intelligently. The problems are presented from the theoretical point of view, without such practical examples as would be helpful for those not acquainted with mathematics. The mathematical justification for the techniques is given. As a somewhat advanced treatment of the design and analysis of experiments, this volume will be interesting and helpful for many who approach statistics theoretically as well as practically. With emphasis on the \"why,\" and with description given broadly, the author relates the subject matter to the general theory of statistics and to the general problem of experimental inference. MARGARET J. ROBERTSON

The Design and Analysis of Experiments

Bayesian inference of phylogeny using Markov chain Monte Carlo (MCMC) plays a central role in understanding evolutionary history from molecular sequence data. Visualizing and analyzing the MCMC-generated samples from the posterior distribution is a key step in any non-trivial Bayesian inference. We present the software package Tracer (version 1.7) for visualizing and analyzing the MCMC trace files generated through Bayesian phylogenetic inference. Tracer provides kernel density estimation, multivariate visualization, demographic trajectory reconstruction, conditional posterior distribution summary, and more. Tracer is open-source and available at http://beast.community/tracer.

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Posterior Summarization in Bayesian Phylogenetics Using Tracer 1.7.

1. Introduction and Overview. 2. Detecting Influential Observations and Outliers. 3. Detecting and Assessing Collinearity. 4. Applications and Remedies. 5. Research Issues and Directions for Extensions. Bibliography. Author Index. Subject Index.

Regression Diagnostics: Identifying Influential Data and Sources of Collinearity

Evolution and ecology of influenza A viruses.

Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are two highly transmissible and pathogenic viruses that emerged in humans at the beginning of the 21st century. Both viruses likely originated in bats, and genetically diverse coronaviruses that are related to SARS-CoV and MERS-CoV were discovered in bats worldwide. In this Review, we summarize the current knowledge on the origin and evolution of these two pathogenic coronaviruses and discuss their receptor usage; we also highlight the diversity and potential of spillover of bat-borne coronaviruses, as evidenced by the recent spillover of swine acute diarrhoea syndrome coronavirus (SADS-CoV) to pigs. Coronaviruses have a broad host range and distribution, and some highly pathogenic lineages have spilled over to humans and animals. Here, Cui, Li and Shi explore the viral factors that enabled the emergence of diseases such as severe acute respiratory syndrome and Middle East respiratory syndrome.

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Origin and evolution of pathogenic coronaviruses

Chapter 48 – Rabies Management in Wild Carnivores

Rabies is one of the oldest known zoonoses. Recognized etiological agents consist of at least 15 proposed species of lyssaviruses with primary reservoirs residing in the Orders Carnivora and Chiroptera. A plethora of viral variants, maintained by a diverse set of abundant hosts, presents a formidable challenge to a strict concept of true disease eradication. Despite the availability of affordable and efficacious animal and human vaccines, today however dog rabies continues to escalate unabated across much of Asia and Africa, causing millions of suspect human exposures and tens of thousands of human rabies deaths annually. By identifying what hampers global human rabies elimination this chapter emphasizes that, given the global epidemiology of rabies, the “One Health” concept is key to solving the problem. Next to state of the art human rabies prevention, immunization and experimental therapy, it is obvious that human rabies can only be eliminated through rabies control at the animal source. This ‘paradigm shift’, however, needs new grassroot initiatives as well as political will and the closing of ranks of all stakeholders in the near future.

Elimination of Rabies : A Missed Opportunity

The common vampire bat (Desmodus rotundus) is a hematophagous species responsible for paralytic rabies and bite damage that affects livestock, humans and wildlife from Mexico to Argentina. Current measures to control vampires, based upon coumarin-derived poisons, are not used extensively due in part to the high cost of application, risks for bats that share roosts with vampires and residual environmental contamination. Observations that vampire bat bites may induce resistance in livestock against vampire bat salivary anticoagulants encourage research into novel vaccine-based alternatives particularly focused upon increasing livestock resistance to vampire salivary components. We evaluated the action of vampire bat saliva-Freund’s incomplete adjuvant administered to sheep with anticoagulant responses induced by repeated vampire bites in a control group and examined characteristics of vampire bat salivary secretion. We observed that injections induced a response against vampire bat salivary anticoagulants stronger than by repeated vampire bat bites. Based upon these preliminary findings, we hypothesize the utility of developing a control technique based on induction of an immunologically mediated resistance against vampire bat anticoagulants and rabies virus via dual delivery of appropriate host and pathogen antigens. Fundamental characteristics of host biology favor alternative strategies than simple culling by poisons for practical, economical, and ecologically relevant management of vampire populations within a One Health context.

https://www.mdpi.com/1999-4915/13/3/515/pdf

Towards Development of an Anti-Vampire Bat Vaccine for Rabies Management: Inoculation of Vampire Bat Saliva Induces Immune-Mediated Resistance.

Rabies, a zoonotic encephalitis due to transmission of a lyssavirus, such as rabies virus (RABV), has the highest case fatality of any infectious disease. A global program for the elimination of human rabies caused by dogs is proposed for realization by 2030. Sensitive, specific, and inexpensive diagnostic tests are necessary for enhanced surveillance to detect infection, inform public health and veterinary professionals during risk assessments of exposure, and support overall programmatic goals. Multiple laboratory techniques are used to confirm a suspect case of rabies. One method for the detection of lyssavirus antigens within the brain is the direct rapid immunohistochemical test (dRIT), using light microscopy, and suitable for use under field conditions. Besides dogs, other major RABV reservoirs reside among mammalian mesocarnivores and bats. To date, use of the dRIT has been applied primarily for the diagnosis of RABV in suspect mesocarnivores. The purpose of this study was to assess the usefulness of the dRIT to the diagnosis of rabies in bats, compared to the gold-standard, the direct fluorescent antibody test (DFAT). Brains of 264 suspect bats, consisting of 21 species from Arizona and Texas, were used in the evaluation of the dRIT. The overall sensitivity of the dRIT was 100% (0.969–1.0, 95% CI) and the specificity was 94.6% (0.896–0.976, 95% CI), comparable to the DFAT. This preliminary study demonstrated the utility of the dRIT in the confirmation of RABV infection in bats. Future studies should include additional geographic, lyssavirus, and mammalian species representations for broader application during enhanced rabies surveillance, with incorporation of any potential adjustments to standard protocols, as needed.

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Use of a Direct, Rapid Immunohistochemical Test for Diagnosis of Rabies Virus in Bats

Rabies is a significant neglected vaccine-preventable disease that is global in distribution. Multiple biologics are utilized in routine prevention and control of this zoonosis. Currently, rabies vaccines are used to interrupt a productive viral encephalitis before or after pathogen exposure in humans and animals. In addition, rabies immune globulins are used as part of prophylaxis after human exposure to a known or suspect animal. Such rabid animals are diagnosed based upon antigenic detection in the brain by selective antibody conjugates. Although experimental proof of concept has been demonstrated in a variety of systems, to date no plant-produced biologics have been licensed for such applications in rabies surveillance, prevention or control. In addition, given the breadth of the host spectrum, there are multiple domestic and wild mammalian species that lack specific vaccines and the cross reactivity of existing products is limited by considerable viral diversity. Hence, if safe, effective and inexpensive biologics may be produced in plants, especially for oral delivery, there is a considerable global niche to fill within the realms of public health, veterinary medicine and conservation biology.

Charles E. Rupprecht

Papers

Chapter 48 – Rabies Management in Wild Carnivores

Elimination of Rabies : A Missed Opportunity

Towards Development of an Anti-Vampire Bat Vaccine for Rabies Management: Inoculation of Vampire Bat Saliva Induces Immune-Mediated Resistance.

Use of a Direct, Rapid Immunohistochemical Test for Diagnosis of Rabies Virus in Bats

Rabies and Related Lyssaviruses