Transmission of canine transmissible venereal tumour between two dogs in the UK.

Canine transmissible venereal tumour (CTVT) is a contagious cancer spread by transfer of living cancer cells. Occasional cases are observed in the UK in dogs imported from endemic regions. Here, we report a case of imported canine transmissible venereal tumour that was transmitted to a second dog within the UK. Transmission of genital canine transmissible venereal tumour occurred despite neutered status of the second dog. The aggressive course of disease in both cases, which included metastasis, resistance to therapeutic interventions and ultimate euthanasia of both dogs, is described. The diagnosis of canine transmissible venereal tumour was made using a combination of cytology, histology, immunohistochemistry and PCR to detect the LINE-MYC rearrangement. Practitioners unfamiliar with canine transmissible venereal tumour are reminded of this disease of concern, particularly when imported dogs are placed in multi-dog households, irrespective of neuter status.

Prospective clinical trial of masitinib mesylate treatment for advanced stage III and IV canine malignant melanoma.

OBJECTIVE: To investigate efficacy of masitinib mesylate for the treatment of advanced malignant melanoma in dogs. MATERIALS AND METHODS: Prospective clinical trial on 17 dogs with stage III and IV malignant melanoma (two digital, one anal and 14 oral mucosal). Only dogs with advanced gross disease for which the owner declined conventional treatment or dogs with progressive tumour despite conventional treatment were included. RESULTS: There was a partial response in two dogs, stable disease in seven and tumour progression in eight dogs. Median survival time for all 17 dogs was 119 days (range 21-255). Masitinib was generally well-tolerated but grade 2 anaemia, grade 1 neutropenia, grade 1 diarrhoea and grade 2 anorexia were observed in one dog each. CLINICAL SIGNIFICANCE: There was only mild effectiveness in end-stage disease, indicating that masitinib mesylate is not an appropriate sole-agent option for treatment of advanced malignant melanoma in dogs.

Idiopathic sterile pyogranuloma in three domestic cats.

Pyogranulomatous inflammation has been extensively described in cats, in particular in cases of feline infectious peritonitis and also associated with Mycobacteria, Actinomyces, Nocardia, Rhodococcus and fungal infections. Idiopathic sterile pyogranulomatous dermatitis has also been described. In this case series we describe the clinical presentation, histopathology and outcome of three cases of feline idiopathic sterile steroid-responsive pyogranuloma with different presentation and different locations of the lesion, but with the common feature of having a mass with no superficial skin involvement.

Significant advances in veterinary oncology - 60 years on.

The first edition of the Journal of Small Animal Practice published in February 1960, contained a paper entitled "Recent Treatments of Malignant Neoplasia" by Dr Larry Owen. Now we have reached the 60th anniversary of JSAP, that article provides a baseline from which to review subsequent advances in veterinary oncology, which now includes worldwide networks that have resulted in veterinary oncology becoming the multidisciplinary speciality that it is today. There certainly have been many advances in understanding of the pathology and epidemiology of animal cancers and in methods of diagnosis and treatment. However, the subject has become so large and diverse that not all aspects can be covered in detail here. It should also be acknowledged that there are still many gaps in knowledge in this field and that, because of a lack of randomised clinical trials, the evidence base for what is often regarded as "standard of care" is weak.

Geographic distribution and environmental risk factors of lymphoma in dogs under primary-care in the UK.

OBJECTIVES: To integrate external data sources with VetCompass postcode data to explore the spatial distribution and examine potential associations with environmental risk factors in dogs diagnosed with lymphoma at primary care veterinary practices. MATERIALS AND METHODS: Cases of lymphoma were identified from electronic patient records of 455,553 dogs under primary veterinary care during 2013 in the UK. Cases were defined as either laboratory-confirmed or non-laboratory-confirmed. Disease maps at the postcode-district level were used to define the geographic distribution of lymphoma incidence and spatial clustering was explored. Environmental risk factors from external data sources were transferred to a compatible format and logistic regression modelling was used to examine associations between environmental herbicide, fungicide and radon concentrations with lymphoma. RESULTS: From the denominator population of 455,553 dogs, 279 lymphoma cases (187 with laboratory confirmation and 93 without) were identified. Heterogeneous geographic variation was observed with weak evidence of clustering around London and the south-west of England. Herbicide and fungicide exposures were weakly associated with a diagnosis of lymphoma in the univariable analysis. After accounting for the age at diagnosis and breed in the multivariable analysis, herbicide exposure was associated with a diagnosis of lymphoma. CLINICAL SIGNIFICANCE: The heterogeneous distribution of lymphoma in UK dogs provides further evidence for geographic variation of lymphoma, perhaps in part associated with underlying environmental risk factors. The results suggest an association between environmental herbicide and canine lymphoma.

Incidence and risk factors for the diagnosis of lymphoma in dogs in UK primary-care practice.

OBJECTIVES: To identify the incidence, risk factors and presenting signs of lymphoma in dogs presenting to primary-care practice in the UK using analysis of data within the VetCompass™ programme. MATERIALS AND METHODS: Case records from the VetCompass™ programme from primary-care practices in the UK were searched for newly diagnosed lymphoma in dogs within a 1-year period: 2013. Diagnosis was based on clinical records with or without laboratory confirmation. Signalment was evaluated as risk factors for lymphoma diagnosis using multivariable logistic regression. RESULTS: There were 286 presumed newly diagnosed cases identified during 2013 from 455,553 dogs (overall incidence risk 63 of 100,000 dogs per year) of which 193 (67%) were laboratory confirmed (42 of 100,000 dogs per year). Advanced age, dogs older than 12 years, dogs weighing more than 30 kg and some specific breeds were significantly associated with lymphoma diagnosis. Only 18 dogs (6%) of the population identified were referred to a specialist clinic. CLINICAL SIGNIFICANCE: This study concurs with others that age, bodyweight and breed are significant risk factors for lymphoma. Results of this study highlight: (1) the low number of dogs with lymphoma that are referred to specialists in the UK and (2) that few dogs undergo immunophenotyping (which can carry prognostic importance), emphasising the importance of epidemiological programmes that evaluate diseases presented to primary-care veterinarians.

Spotting Zika spots: descriptive features of the rash used in 66 published cases.

Zika virus (ZV) is an important emerging infection. Rash is a key feature, but the summative literature lacks description of the rash beyond 'maculopapular'. Our aim was to identify the cutaneous features described in the published literature. A literature search using defined terms for ZV cases reports and series was performed on the OVID, Clinical Key and University of Dundee's e-library journals databases in December 2016; a later case report was included while the paper was under review. Diagnosis in all cases was via PCR. Exclusion criteria were Zika cases without rash or omitting any description of the rash. Ocular features (conjunctivitis) were not included. In total, 42 publications with 66 cases met the criteria. The most frequent descriptive features included maculopapular (59%), lower limb petechial purpura (11%) and erythematous/red (9%). Pruritus was described in 44% and tenderness in 3%. Lesions were located on the trunk (29%), limbs (5% arms, 11% both arms and legs), face (17%) and extremities (14%) or were diffuse/generalized (12%). There was facial sparing in 3%. Other features were centrifugal spread (6%), palmar and/or plantar involvement (6%), palmoplantar desquamation (2%) and malar erythema with oedema (2%). Mucosal features included gingival bleeding (11%), oral haemorrhagic blisters (8%) and painful blisters/vesicles (4%). Oedema/swelling was described in the upper limbs (5%), lower limbs (5%) and both (3%). Mean rash duration was 6 days (range 3-11 days). The ZV exanthema is most frequently maculopapular, pruritic, sometimes with centrifugal spread from the trunk to extremities. This may include lower limb petechial purpura, palmoplantar lesions, oedema of limb extremities, and gingival bleeding or painful oral bullae. As ZV becomes more prevalent, recognition of the clinical features will enable earlier diagnosis and appropriate testing.

Evaluation of Histological, Immunohistochemical, Clinical and Genetic Prognostic Factors Associated with the Response of Canine Mast Cell Tumours to Glucocorticotherapy.

Mast cell tumours (MCTs) are one of the most frequent neoplasms in dogs. Glucocorticoids (GCs) are widely used in the management of this disease, although no guidelines for their use have been established. The aim of this study was to evaluate the correlation of MCT prognostic factors with measurable response to GCs. This retrospective study included 60 dogs treated with prednisone or prednisolone prior to surgical biopsy of MCT. Incisional or excisional biopsy was performed 7-14 days after initiation of GC therapy. Histopathology, immunohistochemical labelling for Ki67 and KITr, and polymerase chain reaction for the c-KIT gene were performed. Partial response occurred in 63.3% of cases (38/60), while 36.7% (22/60) did not respond. A response to GCs was correlated with lower stage of the disease, low histological grade, lower pattern of KITr expression and Ki67 score. Response to GCs was positively correlated with well-established favourable prognostic factors.

The future of radiotherapy in small animals - should the fractions be coarse or fine?

Radiation therapy has been used to treat animal cancers for more than 100 years. Clinical experiences and experimental results have been widely published and provide a basis for the recognition of radiation therapy as an integral component of multimodal cancer management in veterinary oncology. As the expectations of pet owners and the demand for treatment of companion animals with cancer have increased, veterinary oncology itself has undergone dramatic advances in the past several decades both in terms of improved diagnostics and treatments, including increased accessibility of radiation therapy. Synchronous with development of the specialism of veterinary radiation oncology, confusion and controversy have arisen with regard to distinguishing between different types of radiotherapy and methods of treatment delivery. Importantly, the confusion extends beyond semantics, and includes opinionated debate about defining which forms of therapy (if any at all) are optimal for a given patient. This exemplifies how, despite marks of maturity including age and a robust publication history, the field of veterinary radiation oncology is in some ways still in its infancy. The purpose of this article is to review the evidence base for daily (fine) fractionation versus weekly (coarse) hypofractionation in veterinary oncology, using selected tumour types as examples.

A model based bayesian solution for characterization of complex damage scenarios in aerospace composite structures.

Ultrasonic damage detection and characterization is commonly used in nondestructive evaluation (NDE) of aerospace composite components. In recent years there has been an increased development of guided wave based methods. In real materials and structures, these dispersive waves result in complicated behavior in the presence of complex damage scenarios. Model-based characterization methods utilize accurate three dimensional finite element models (FEMs) of guided wave interaction with realistic damage scenarios to aid in defect identification and classification. This work describes an inverse solution for realistic composite damage characterization by comparing the wavenumber-frequency spectra of experimental and simulated ultrasonic inspections. The composite laminate material properties are first verified through a Bayesian solution (Markov chain Monte Carlo), enabling uncertainty quantification surrounding the characterization. A study is undertaken to assess the efficacy of the proposed damage model and comparative metrics between the experimental and simulated output. The FEM is then parameterized with a damage model capable of describing the typical complex damage created by impact events in composites. The damage is characterized through a transdimensional Markov chain Monte Carlo solution, enabling a flexible damage model capable of adapting to the complex damage geometry investigated here. The posterior probability distributions of the individual delamination petals as well as the overall envelope of the damage site are determined.

First Searches for Axions and Axionlike Particles with the LUX Experiment.

The first searches for axions and axionlike particles with the Large Underground Xenon experiment are presented. Under the assumption of an axioelectric interaction in xenon, the coupling constant between axions and electrons g_{Ae} is tested using data collected in 2013 with an exposure totaling 95 live days ×118 kg. A double-sided, profile likelihood ratio statistic test excludes g_{Ae} larger than 3.5×10^{-12} (90% C.L.) for solar axions. Assuming the Dine-Fischler-Srednicki-Zhitnitsky theoretical description, the upper limit in coupling corresponds to an upper limit on axion mass of 0.12 eV/c^{2}, while for the Kim-Shifman-Vainshtein-Zhakharov description masses above 36.6 eV/c^{2} are excluded. For galactic axionlike particles, values of g_{Ae} larger than 4.2×10^{-13} are excluded for particle masses in the range 1-16 keV/c^{2}. These are the most stringent constraints to date for these interactions.

Temporal and spatial heterogeneity in milk and immune-related gene expression during mammary gland involution in dairy cows.

The aim of this study was to investigate heterogeneity in tissue morphology, milk protein and immune-related gene expression, and apoptosis of epithelial cells in the lactating and involuting mammary glands of the dairy cow. Mammary tissue from different regions of the gland (alveolar, cisternal, and peripheral) was collected postmortem from nonpregnant, pasture-fed, Holstein-Friesian primiparous cows in mid-lactation that were killed at different time points postmilking: 0, 6, 12, 18, 24, 36, and 72 h (n = 6 per time point). The CSN1NS1 and LALBA mRNA was decreased in alveolar, cisternal, and peripheral tissue by 12 to 36 h postmilking. In contrast, lactoferrin (LF) and mammary serum amyloid A3 (M-SAA3) mRNA was increased in these regions by 36 to 72 h. During lactation, more variability was present in gene expression in alveolar tissue between cows and between quarters within a cow, than within quarters. Histological analysis indicated the alveolar tissue from lactating cows was mostly uniform in structure; however, in situ hybridization indicated that although most of the alveolar tissue expressed milk proteins, the level of expression varied within and between alveoli. This heterogeneity became more pronounced with involution and with increasing regions of alveoli expressing lactoferrin, indicating that alveoli enter involution asynchronously. The peripheral and cisternal tissue had more variability in gene expression between cows compared with the alveolar tissue. The M-SAA3 signal was more intense in the cisternal tissue and less intense than the peripheral compartment compared with LF particularly in the earlier time points. In addition, between cows within the later time points, differences were observed in tissue morphology, the levels of milk protein and immune-related gene expression, and phosphorylated signal transducer and activator of transcription (STAT) 5-P and STAT3-P proteins, and degree of apoptosis, indicating that involution of the mammary gland occurs at different rates between cows. Understanding the mechanisms initiating the process of involution of the mammary gland provides an opportunity for enhancing milk production of the dairy cow.

Limits on Spin-Dependent WIMP-Nucleon Cross Section Obtained from the Complete LUX Exposure.

We present experimental constraints on the spin-dependent WIMP-nucleon elastic cross sections from the total 129.5 kg yr exposure acquired by the Large Underground Xenon experiment (LUX), operating at the Sanford Underground Research Facility in Lead, South Dakota (USA). A profile likelihood ratio analysis allows 90% C.L. upper limits to be set on the WIMP-neutron (WIMP-proton) cross section of σ_{n}=1.6×10^{-41} cm^{2} (σ_{p}=5×10^{-40} cm^{2}) at 35 GeV c^{-2}, almost a sixfold improvement over the previous LUX spin-dependent results. The spin-dependent WIMP-neutron limit is the most sensitive constraint to date.

Comparing intra-articular CTXII levels assessed via magnetic capture or lavage in a rat knee osteoarthritis model.

OBJECTIVE: Parallel measures of osteoarthritis (OA) across species can help evaluate OA models relative to humans. Toward this need, our group recently developed a magnetic nanoparticle-based technology, termed magnetic capture, to analyze biomarkers within a rat knee. The objectives of this study were to directly compare magnetic capture to lavage, and assess c-telopeptide of collagen type II (CTXII) in the rat medial meniscus transection (MMT) model of knee OA. DESIGN: MMT surgery was performed in 30 male Lewis rats (3 months, 250 g). Using lavage or magnetic capture, CTXII was assessed in the OA-affected and contralateral knee at 1 week (n = 6 per group) or 4 weeks (n = 8 per group) after surgery. RESULTS: While lavage detected elevated CTXII concentrations in the OA-affected knee at 1 week (P = 0.002), magnetic capture detected elevated CTXII levels in the OA-affected knee at 4 weeks (P = 0.016). While magnetic capture did not detect significant elevation of CTXII at week 1, five of six rats evaluated with magnetic capture had higher CTXII levels in the OA-affected joint relative to the contralateral limb. Moreover, with magnetic capture, CTXII levels increased from 1 week to 4 weeks, corresponding to histological damage. CTXII concentrations evaluated via lavage were relatively constant across time. CONCLUSIONS: Magnetic capture and lavage evaluate CTXII in different ways: Magnetic capture measures total CTXII in the joint, while lavage measures concentration. Our data indicate magnetic capture may be advantageous at later time points, where CTXII can be diluted by effusions.

Glycolysis inhibition improves photodynamic therapy response rates for equine sarcoids.

Photodynamic therapy (PDT) holds great promise in treating veterinary and human dermatological neoplasms, including equine sarcoids, but is currently hindered by the amount of photosensitiser and light that can be delivered to lesions thicker than around 2 mm, and by the intrinsic antioxidant defences of tumour cells. We have developed a new PDT technique that combines an efficient transdermal penetration enhancer solution, for topical delivery of 5-aminolevulinic acid (ALA) photosensitiser, with acute topical post-PDT application of the glycolysis inhibitor lonidamine. We show that the new PDT combination treatment selectively kills sarcoid cells in vitro, with repeated rounds of treatment increasing sarcoid sensitisation to PDT. In vivo, ALA PDT followed by 600 µM lonidamine substantially improves treatment outcomes for occult, verrucous, nodular and fibroblastic sarcoids after 1 month (93% treatment response in 27 sarcoids), compared with PDT using only ALA (14% treatment response in 7 sarcoids).

Results from a Search for Dark Matter in the Complete LUX Exposure.

We report constraints on spin-independent weakly interacting massive particle (WIMP)-nucleon scattering using a 3.35×10^{4} kg day exposure of the Large Underground Xenon (LUX) experiment. A dual-phase xenon time projection chamber with 250 kg of active mass is operated at the Sanford Underground Research Facility under Lead, South Dakota (USA). With roughly fourfold improvement in sensitivity for high WIMP masses relative to our previous results, this search yields no evidence of WIMP nuclear recoils. At a WIMP mass of 50 GeV c^{-2}, WIMP-nucleon spin-independent cross sections above 2.2×10^{-46} cm^{2} are excluded at the 90% confidence level. When combined with the previously reported LUX exposure, this exclusion strengthens to 1.1×10^{-46} cm^{2} at 50 GeV c^{-2}.

T Lymphocytes in Histiocytic Sarcomas of Flat-Coated Retriever Dogs.

Flat-Coated Retriever dogs are predisposed to the development of histiocytic sarcoma (HS), a poorly differentiated, highly malignant neoplasm. The authors have previously documented a significant lymphocytic infiltrate in such tumors. The objective of this study was to examine the presence and expression of regulatory T cells in HS tumor samples. Forty tumors were included in this study. All tumors were immunolabeled for CD3, CD79a, CD25, CD45RA, and FOXP3. The proportion of positive cells was compared between tumors presenting as a localized primary soft tissue mass (soft tissue origin HS) and disseminated HS affecting viscera, especially the spleen (splenic origin HS). By immunohistochemistry, 95% of infiltrating T cells were positive for Foxp3 in all sections, suggesting the presence of regulatory T cells. The proportion of cells positive for FOXP3 was higher in the tumors arising in soft tissues, whereas the proportion of CD45RA-positive cells was higher in the splenic origin HS. Canine HS has an aggressive clinical behavior and is uniformly fatal. The difference in the proportion of tumor-infiltrating lymphocytes positive for these 2 markers in the 2 locations may represent differences in tumor microenvironment between the 2 sites.

Housing characteristics and indoor air quality in households of Alaska Native children with chronic lung conditions.

Alaska Native children experience high rates of respiratory infections and conditions. Household crowding, indoor smoke, lack of piped water, and poverty have been associated with respiratory infections. We describe the baseline household characteristics of children with severe or chronic lung disease participating in a 2012-2015 indoor air study. We monitored indoor PM2.5, CO2 , relative humidity %, temperature, and VOCs and interviewed caregivers about children's respiratory symptoms. We evaluated the association between reported children's respiratory symptoms and indoor air quality indicators using multiple logistic regression analysis. Compared with general US households, study households were more likely overcrowded 73% (62%-82%) vs 3.2% (3.1%-3.3%); had higher woodstove use as primary heat source 16% (9%-25%) vs 2.1% (2.0%-2.2%); and higher proportion of children in a household with a smoker 49% (38%-60%) vs 26.2% (25.5%-26.8%). Median PM2.5 was 33 µg/m3 . Median CO2 was 1401 ppm. VOCs were detectable in all homes. VOCs, smoker, primary wood heat, and PM2.5>25 µg/m3 were associated with higher risk for cough between colds; VOCs were associated with higher risk for wheeze between colds and asthma diagnosis. High indoor air pollutant levels were associated with respiratory symptoms in household children, likely related to overcrowding, poor ventilation, woodstove use, and tobacco smoke.