Pathogenesis of feline enteric coronavirus infection.

Fifty-one specific pathogen-free (SPF) cats 10 weeks to 13 years of age were infected with a cat-to-cat fecal-oral passed strain of feline enteric coronavirus (FECV). Clinical signs ranged from unapparent to a mild and self-limiting diarrhea. Twenty-nine of these cats were FECV naïve before infection and followed sequentially for fecal virus shedding and antibody responses over a period of 8-48 months. Fecal shedding, as determined by real-time polymerase chain reaction (RT-PCR) from rectal swabs, appeared within a week and was significantly higher in kittens than older cats. FECV shedding remained at high levels for 2-10 months before eventually evolving into one of three excretion patterns. Eleven cats shed the virus persistently at varying levels over an observation period of 9-24 months. Eleven cats appeared to have periods of virus shedding interlaced with periods of non-shedding (intermittent or recurrent shedders), and seven cats ceased shedding after 5-19 months (average 12 months). There was no change in the patterns of virus shedding among cats that were excreting FECV at the time of a secondary challenge exposure. Four cats, which had ceased shedding, re-manifested a primary type infection when secondarily infected. Cats with higher feline coronavirus (FCoV) antibody titers were significantly more likely to shed virus, while cats with lower titers were significantly less likely to be shedding. Twenty-two kittens born to experimentally infected project queens began shedding virus spontaneously, but never before 9-10 weeks of age. Natural kittenhood infections appeared to be low grade and abortive. However, a characteristic primary type infection occurred following experimental infection with FECV at 12-15 weeks of age. Pregnancy, parturition and lactation had no influence on fecal shedding by queens. Methylprednisolone acetate treatment did not induce non-shedders to shed and shedders to increase shedding

Guidelines for the management of the foot health problems associated with rheumatoid arthritis

Background. Rheumatoid arthritis (RA) as a chronic systemic disease, commonly affects the feet, impacting negatively on patients' quality of life. Specialist podiatrists have a prime role to play in the assessment and management of foot and ankle problems within this patient group. However, it has been identified that in many areas there is no specialist podiatry service, with many patients being managed by non‐specialist podiatrists. Therefore, the North West Clinical Effectiveness Group for the Foot in Rheumatic Diseases (NWCEG) identified the need to develop ‘practitioner facing’ guidelines for the management of specific foot health problems associated with RA. Methods. Members of a guideline development group from the NWCEG each reviewed the evidence for specific aspects of the assessment and management of foot problems. Where evidence was lacking, ‘expert opinion’ was obtained from the members of the NWCEG and added as a consensus on current and best practice. An iterative approach was employed, with the results being reviewed and revised by all members of the group and external reviewers before the final guideline document was produced. Results. The management of specific foot problems (callus, nail pathology, ulceration) and the use of specific interventions (foot orthoses, footwear, patient education, steroid injection therapy) are detailed and standards in relation to each are provided. A diagrammatic screening pathway is presented, with the aim of guiding nonspecialist podiatrists through the complexity of assessing and managing those patients with problems requiring input from a specialist podiatrist and other members of the rheumatology multidisciplinary team. Conclusion. This pragmatic approach ensured that the guidelines were relevant and applicable to current practice as ‘best practice’, based on the available evidence from the literature and consensus expert opinion. These guidelines provide both specialist and non‐specialist podiatrists with the essential and ‘gold standard’ aspects of managing people with RA‐related foot problems

Genetic susceptibility to feline infectious peritonitis in Birman cats.

Genetic factors are presumed to influence the incidence of feline infectious peritonitis (FIP), especially among pedigreed cats. However, proof for the existence of such factors has been limited and mainly anecdotal. Therefore, we sought evidence for genetic susceptibility to FIP using feline high density single nucleotide polymorphism (SNP) arrays in a genome-wide association study (GWAS). Birman cats were chosen for GWAS because they are highly inbred and suffer a high incidence of FIP. DNA from 38 Birman cats that died of FIP and 161 healthy cats from breeders in Denmark and USA were selected for genotyping using 63K SNPs distributed across the feline genome. Danish and American Birman cats were closely related and the populations were therefore combined and analyzed in two manners: (1) all cases (FIP) vs. all controls (healthy) regardless of age, and (2) cases 1½ years of age and younger (most susceptible) vs. controls 2 years of age and older (most resistant). GWAS of the second cohort was most productive in identifying significant genome-wide associations between case and control cats. Four peaks of association with FIP susceptibility were identified, with two being identified on both analyses. Five candidate genes ELMO1, RRAGA, TNFSF10, ERAP1 and ERAP2, all relevant to what is known about FIP virus pathogenesis, were identified but no single association was fully concordant with the disease phenotype. Difficulties in doing GWAS in cats and interrogating complex genetic traits were discussed

Scattering statistics of rock outcrops: Model-data comparisons and Bayesian inference using mixture distributions

The probability density function of the acoustic field amplitude scattered by the seafloor was measured in a rocky environment off the coast of Norway using a synthetic aperture sonar system, and is reported here in terms of the probability of false alarm. Interpretation of the measurements focused on finding appropriate class of statistical models (single versus two-component mixture models), and on appropriate models within these two classes. It was found that two-component mixture models performed better than single models. The two mixture models that performed the best (and had a basis in the physics of scattering) were a mixture between two K distributions, and a mixture between a Rayleigh and generalized Pareto distribution. Bayes' theorem was used to estimate the probability density function of the mixture model parameters. It was found that the K-K mixture exhibits significant correlation between its parameters. The mixture between the Rayleigh and generalized Pareto distributions also had significant parameter correlation, but also contained multiple modes. We conclude that the mixture between two K distributions is the most applicable to this dataset.Comment: 15 pages, 7 figures, Accepted to the Journal of the Acoustical Society of Americ

Evidence for induction of humoral and cytotoxic immune responses against devil facial tumor disease cells in Tasmanian devils (Sarcophilus harrisii) immunized with killed cell preparations

Available online 20 February 2015Tasmanian devils (Sarcophilus harrisii) risk extinction from a contagious cancer, devil facial tumour disease (DFTD) in which the infectious agent is the tumor cell itself. Because devils are unable to produce an immune response against the tumor cells no devil has survived 'infection'. To promote an immune response we immunized healthy devils with killed DFTD tumor cells in the presence of adjuvants. Immune responses, including cytotoxicity and antibody production, were detected in five of the six devils. The incorporation of adjuvants that act via toll like receptors may provide additional signals to break 'immunological ignorance'. One of these devils was protected against a challenge with viable DFTD cells. This was a short-term protection as re-challenge one year later resulted in tumor growth. These results suggest that Tasmanian devils can generate immune responses against DFTD cells. With further optimization of immune stimulation it should be possible to protect Tasmanian devils against DFTD with an injectable vaccine.A. Kreiss, G.K. Brown, C. Tovar, A.B. Lyons, G.M. Wood