Malignant catarrhal fever in sika deer (Cervus nippon) in the UK

[Extract]\ud Malignant catarrhal fever (MCF) is a viral disease characterised by lymphoproliferation, vasculitis and erosive-ulcerative mucosal and cutaneous lesions (Brown and others 2007, Russell and others 2009); it is commonly fatal. The antigenic 15-A epitope and base similarity in conserved regions have been used to define the group of MCF-causing viruses (Li and others 2001) and four viruses from the genus Rhadinovirus, subfamily Gammaherpesvirinae, are currently associated with clinical MCF. The disease has been described in over 30 species of wild and domestic ruminant species (Heuschele 1988). Based on the host in which the virus was originally detected, the MCF-causing viruses include alcelaphine herpesvirus type 1 (AlHV-1) from wildebeest, ovine herpesvirus type 2 (OvHV-2) from domestic sheep, whose reservoir host remains unidentified, the MCF-causing virus in white-tailed deer (Odocoileus virginianus) (Li and others 2000), and caprine herpesvirus type 2 (CpHV-2), identified from domestic goats and a pig in Germany (Chmielewicz and others 2001), and from goats in North America (Li and others 2001). These viruses are considered to be usually transmitted directly from the reservoir host

Direct binding between Orai1 and AC8 mediates dynamic interplay between Ca2+ and cAMP signaling

The interplay between calcium ion (Ca(2+)) and cyclic adenosine monophosphate (cAMP) signaling underlies crucial aspects of cell homeostasis. The membrane-bound Ca(2+)-regulated adenylyl cyclases (ACs) are pivotal points of this integration. These enzymes display high selectivity for Ca(2+) entry arising from the activation of store-operated Ca(2+) (SOC) channels, and they have been proposed to functionally colocalize with SOC channels to reinforce crosstalk between the two signaling pathways. Using a multidisciplinary approach, we have identified a direct interaction between the amino termini of Ca(2+)-stimulated AC8 and Orai1, the pore component of SOC channels. High-resolution biosensors targeted to the AC8 and Orai1 microdomains revealed that this protein-protein interaction is responsible for coordinating subcellular changes in both Ca(2+) and cAMP. The demonstration that Orai1 functions as an integral component of a highly organized signaling complex to coordinate Ca(2+) and cAMP signals underscores how SOC channels can be recruited to maximize the efficiency of the interplay between these two ubiquitous signaling pathways

Early outcomes of thymoglobulin and basiliximab induction in kidney transplantation : Application of statistical approaches to reduce bias in observational comparisons

Background: Retrospective comparison of treatment-related kidney transplant outcomes may be facilitated by multivariable statistical adjustments and case-matching. Methods: We studied Organ Procurement and Transplantation Network registry data for kidney transplants in 2001 to 2005 managed with thymoglobulin, basiliximab or no antibody induction and discharge maintenance immunosuppression regimens of tacrolimus and mycophenolate mofetil. The primary outcome was the six-month, Food and Drug Administration-approved composite endpoint of rejection, graft failure, or death. Outcomes were according to induction exposure were compared using logistic regression, exposure propensity matching, and outcome risk score matching. Results: All statistical approaches demonstrated lower rates of the six-month triple endpoint with thymoglobulin compared with basiliximab when steroids were present, with approximately 22% adjusted, relative reduction by logistic and 3% absolute reductions by matching approaches. When steroids were absent, risk reduction among thymoglobulin versus basiliximab-treated patients was of larger magnitude but borderline statistical significance. Triple endpoint incidence was lower with both induction regimens compared to no induction across methods. Estimated sample sizes necessary to detect the observed differences between induction types in the presence of steroids in a prospective trial ranged from 1600 to nearly 7000 patients. Conclusions: Consistency of these data across statistical approaches suggests superiority of thymoglobulin compared to basiliximab or no antibody induction therapy for six-month kidney transplant outcomes in the modern immunosuppression era. As the sample sizes necessary to power a prospective superiority trial are likely prohibitive, studies such as these provide clinically relevant information that may not be otherwise attainabl

A Robust Bayesian Approach for Structural Equation Models with Missing Data

robust Bayesian methods, normal/independent distributions, nonlinear structural equation models with covariates, model comparison,