Yu-Mei Chang

• Royal Veterinary College

Background – Fetuin-A aggregates with calcium and phosphate ions to form calciprotein monomers, preventing precipitation (low-density calciprotein particles [L-CPP]). Consolidation of L-CPP with further protein leads to amorphous CPP which transform spontaneously into pro-inflammatory crystalline CPP over time (high-density CPP [H-CPP]). The transi...

There is growing evidence supporting clinically important associations between age at neutering in bitches and subsequent urinary incontinence (UI), although much of this evidence to date is considered weak. Target trial emulation is an innovative approach in causal inference that has gained substantial attention in recent years, aiming to simulate...

Background Plasma total magnesium concentration (tMg) is a prognostic indicator in cats with chronic kidney disease (CKD), shorter survival time being associated with hypomagnesemia. Whether this risk factor is modifiable with dietary magnesium supplementation remains unexplored. Objectives Evaluate effects of a magnesium‐enriched phosphate‐restri...

Immune thrombocytopenia (ITP) is the most common acquired primary hemostatic disorder in dogs. Immune thrombocytopenia less commonly affects cats but is an important cause of mortality and treatment‐associated morbidity in both species. Immune thrombocytopenia remains a diagnosis of exclusion for which diagnostic guidelines are lacking. Primary, or...

Rabies is a highly virulent viral disease that has been associated with large-scale population declines of the endangered African wild dog (Lycaon pictus). Rabies vaccination may be a valuable conservation tool in this species, but studies indicate that a single dose does not always confer protective immunity. We examined 47 serum samples from 22 c...

Background Microscopic nephrocalcinosis is a common pathological feature of chronic kidney disease (CKD) in cats. Detection of macroscopic nephrocalcinosis using ultrasonography and its implications remain unexplored. Objectives Identify risk factors associated with ultrasound‐diagnosed nephrocalcinosis and evaluate the influence of nephrocalcinos...

Background Legislation was introduced in Germany in 2018, requiring bacterial culture and antimicrobial susceptibility testing before the prescription of fluoroquinolones and third‐generation cephalosporins to dogs. We hypothesised that, following this intervention, the number of clinical samples testing positive for methicillin‐resistant Staphyloc...

Background Osteoarthritis of the equine thoracolumbar articular process joints (APJs) has been linked to back pain. Changes are commonly diagnosed through nuclear scintigraphy, radiography and ultrasonography (US). Objectives (1) To assess the agreement of APJ grades between US and computed tomography (CT) images; (2) to assess the effect of locat...

Target trial emulation applies design principles from randomised controlled trials to the analysis of observational data for causal inference and is increasingly used within human epidemiology. Veterinary electronic clinical records represent a potentially valuable source of information to estimate real-world causal effects for companion animal spe...

Background Serum insulin concentration at 60 min (InsulinT60) during an oral sugar test (OST) indicates future laminitis risk and insulin dysregulation (ID). Associations between InsulinT60 and physical and owner‐reported variables may help clinicians select individuals for ID testing. Associations between InsulinT60 and other metabolic markers may...

Background Intestinal fibrosis (IF) is commonly identified on histopathology of intestinal biopsy specimens (IBSp) from cats with chronic inflammatory enteropathy (CIE) however, its clinical relevance is unknown. Objectives Characterize and determine the clinical relevance of IF in cats with CIE. Animals Sixty‐five client‐owned cats diagnosed wit...

Background While immune checkpoint inhibitors (ICIs) have been revolutionary in the treatment of cancer, their administration has been associated with a variety of immune-related adverse events (irAEs), including myasthenia gravis (MG), and Lambert-Eaton myasthenic syndrome (LEMS). Objective To provide a comprehensive synthesis of the evidence sup...

Objective To assess the occurrence of acute kidney injury (AKI) in dogs undergoing cardiac surgery under cardiopulmonary bypass (CPB) and explore associations between traditional and novel serum and urinary biomarkers. Design Prospective cohort study conducted between July 2018 and April 2019. Setting University teaching hospital. Animals Ninete...

Fluoroquinolones (FQ) are commonly used in dogs with bacterial skin infections. Their use as first choice, along with the increased incidence of FQ-resistance, represents a risk to animal and public health. Our study determined minimum inhibitory (MIC) and bactericidal (MBC) concentrations of five FQs in Staphylococcus aureus, Staphylococcus pseudi...

Introduction Myxomatous mitral valve disease (MMVD) is the most common cardiac condition in adult dogs. The disease progresses over several years and affected dogs may develop congestive heart failure (HF). Research has shown that myocardial metabolism is altered in cardiac disease, leading to a reduction in β-oxidation of fatty acids and an increa...

Background Nephrocalcinosis is a pathological feature of chronic kidney disease (CKD). Its pathophysiological implications for cats with CKD are unexplored. Objectives Identify nephrocalcinosis risk factors and evaluate its influence on CKD progression and all‐cause mortality. Animals Fifty‐one euthyroid client‐owned cats with International Renal...

Background: Myasthenia gravis (MG) is an autoimmune disorder of unknown etiology in most patients, in which autoantibodies target components of neuromuscular junctions and impair nerve to muscle transmission. Objective: To provide a synthesis of the evidence examining infectious agents associated with the onset of MG. Hypothesis: We hypothesized th...

Background Blood l‐lactate concentrations are higher in people with developing or established diabetes mellitus and insulin resistance. Objectives To investigate whether blood l‐lactate concentrations are positively correlated with measures of insulin dysregulation (ID) or increased autumnal ACTH concentrations in ponies. Animals Systemically hea...

Background There is limited published information on the outcome for cats where total thyroxine concentration (TT4) remains elevated after treatment with radioactive iodine (RAI). Objective To determine the frequency of, and predictors for, subsequent treatment failure in cats for which TT4 remains elevated at hospital discharge, and to report cli...

Background The effect of assisted enteral feeding on treatment outcome in dogs with protein‐losing enteropathy (PLE) is unknown. Objectives To determine if dogs with inflammatory PLE that had an enteral feeding tube placed had better outcome vs dogs with inflammatory PLE without a feeding tube. Animals Fifty‐seven dogs with inflammatory PLE. Met...

Objectives: Early diagnosis of arterial hypertension is essential to prevent target organ damage. In humans, retinal arteriolar narrowing predicts hypertension. This blinded prospective observational study investigated the retinal vessel diameters in senior and geriatric cats of varying systolic blood pressure (SBP) status and evaluated retinal va...

Background Hypercalcemia is commonly observed in cats with azotemic chronic kidney disease (CKD). Dietary phosphate restriction is considered standard of care but may contribute to the development of hypercalcemia. The optimal dietary management strategy for these cats is unclear. Objectives To describe the effect of feeding a moderately phosphate...

Anesthetics may worsen the outcome of patients undergoing oncologic surgery via immune suppression. This study examines the impact of propofol, ketamine, and alfaxalone on canine peripheral blood lymphocyte (PBL) cytotoxic function in vitro. PBLs isolated from healthy canine blood were cultured in the presence or absence of alfaxalone, propofol, ke...

Myasthenia gravis (MG) is a T cell-dependent, B cell-mediated autoimmune disease. Little is known about its cellular pathogenesis in dogs. This study provides the first preliminary assessment of the frequency of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in the peripheral blood of dogs with seropositive generalized MG....

Background Dietary phosphate restriction improves survival in cats with chronic kidney disease (CKD). However, feeding a phosphate‐restricted diet may disrupt calcium homeostasis leading to hypercalcemia in some cats. Objectives To identify risk factors associated with increasing plasma total calcium (tCa) concentration after transition to a phosp...

Background Cats with chronic kidney disease (CKD) have an increased prevalence of positive urine cultures (PUC). Limited information is available regarding the prognosis of cats with CKD and concurrent PUC. Objective To determine the association of PUC with survival time and disease progression in cats with CKD. Animals Medical records of 509 cat...

Background: Since the epidemiology of canine and feline dermatophytosis might evolve in response to chronological, sociological and ecological factors, the authors studied the occurrence of dermatophyte pathogens over 27 years subsequent to the last major UK survey. Methods: Dermatophyte culture submission records from dogs and cats to the Royal...

Dietary phosphate restriction improves survival in cats with chronic kidney disease (CKD). However, feeding a phosphate‐restricted diet may contribute to development of hypercalcemia. This study aimed to identify risk factors associated with increasing plasma total calcium concentrations (TCa) following transition onto a phosphate‐restricted diet i...

Compromised gut health and dysbiosis in people with heart failure has received a great deal of attention over the last decade. Whether dogs with heart failure have a similar dysbiosis pattern to what is described in people is currently unknown. We hypothesised that dogs with congestive heart failure have quantifiable dysbiosis compared to healthy d...

Gene expression profiling has revealed molecular heterogeneity of diffuse large B cell lymphoma (DLBCL) in both humans and dogs. Two DLBCL subtypes based on cell of origin are generally recognized, germinal center B (GCB)-like and activated B cell (ABC)-like. A pilot study to characterize the transcriptomic phenotype of 11 dogs with multicentric BC...

Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are implicated in the progression and outcome of a variety of pathological states, from cancer to infection. Our previous work has identified three antimicrobial peptides differentially expressed by PMN-MDSCs compared to conventional neutrophils isolated from dogs, mice, and human patie...

Background Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that is increased in azotemic cats with chronic kidney disease (CKD) and predictive of the onset of azotemia in older cats. The introduction of symmetric dimethylarginine (SDMA) as a biomarker of glomerular filtration rate has led to the identification of cats in which SDMA is...

Regulatory T cells (Tregs) are a double-edged regulator of the immune system. Aberrations of Tregs correlate with pathogenesis of inflammatory, autoimmune and neoplastic disorders. Phenotypically and functionally distinct subsets of Tregs have been identified in humans and mice on the basis of their extensive portfolios of monoclonal antibodies (mA...

Methods A randomised non-blinded non-inferiority trial was conducted to determine whether treatment with an unfractionated regimen of oral prednisolone was inferior to a fractionated regimen for dogs with primary immune-mediated haemolytic anaemia. Dogs received the same total daily dose of prednisolone as unfractionated (group 1, starting at 4 mg/...

Chronic kidney disease (CKD) is a frequent diagnosis in cats attending primary care practice and the most frequent cause of death in cats aged over five years, yet there is limited published research for CKD in cats attending primary care practice. This study aimed to estimate the prevalence of CKD and investigate risk factors for diagnosis and sur...

Background: We report the development of a cutaneous melanoma risk algorithm based upon 7 factors; hair colour, skin type, family history, freckling, nevus count, number of large nevi and history of sunburn, intended to form the basis of a self-assessment webtool for the general public. Methods: Predicted odds of melanoma were estimated by analysin...

Mutations in the CDKN2A and CDK4 genes predispose to melanoma. From three case-control studies of cutaneous melanoma, we estimated the prevalence and predictors of these mutations for people from regions with widely differing latitudes and melanoma incidence. Population-based cases and controls from the United Kingdom (1586 cases, 499 controls) and...

Saline to freshwater invasions have become increasingly common in recent years. A key hypothesis is that rates of freshwater invasions have been amplified in recent years by increased food concentration, yet this hypothesis has remained unexplored. We examined whether elevated food concentration could enhance freshwater tolerance, and whether this...

Objective: To assess relationships among serum N-terminal procollagen type III concentration, urinary aldosterone-to-creatinine concentration ratio (UAC), and clinical variables in dogs with myxomatous mitral valve disease (MMVD) and healthy dogs. Animals: 162 dogs with MMVD and 24 healthy control dogs of comparable age and body weight. Procedu...

Objective To examine the frequency and correlates of skin examination behaviors in an international sample of individuals at varying risk of developing melanoma. Design A cross-sectional, web-based survey. Setting Data were collected from the general population over a 20-month period on behalf of the Melanoma Genetics Consortium (GenoMEL). Particip...

We report the determinants of serum levels of vitamin D in a U.K. melanoma case-control study benefitting from detailed exposure and genotyping data. Sun exposure, supplemental vitamin D, and SNPs reported to be associated with serum levels were assessed as predictors of a single serum 25-hydroxyvitamin D3 measurement adjusted for season, age, sex,...

A model has been proposed whereby melanomas arise through two distinct pathways dependent on the relative influence of host susceptibility and sun exposure. Such pathways may explain site-specific patterns of melanoma occurrence. To explore this model, we investigated the relationship between melanoma risk and general markers of acute (recalled sun...

To evaluate whether the addition of a protease inhibitor (PI) to feline plasma improves the temporal stability of N-terminal pro-B-type natriuretic peptide (NT-proBNP). Forty-four EDTA blood samples were collected from 42 cats with cardiac disease or hyperthyroidism. Samples were separated within 15 min of collection and the plasma stored at -80 °C...

CDKN2A mutations confer a substantial risk of cutaneous melanoma; however, the magnitude of risk is uncertain. The study estimated the hazard ratio (HR) and the average age specific cumulative risk (ie, penetrance) of reported melanoma for CDKN2A mutation carriers in case families using a modified segregation analysis of the first and higher degree...

To test the hypothesis that changing the orientation of a thoracic radiograph aids diagnosis of rib fractures, a case-control study was carried out using 120 radiographs of small animal patients with recent thoracic trauma. Six independent observers representing three levels of experience viewed the radiographs in randomized order in conventional a...

A melanoma case-control study was conducted to elucidate the complex relationship between sun exposure and risk. Nine hundred and sixty population-ascertained cases, 513 population and 174 sibling controls recruited in England provided detailed sun exposure and phenotype data; a subset provided serum 25-hydroxyvitamin D(2)+D(3) levels. Phenotypes a...

Post-weaning multi-systemic wasting syndrome (PMWS) causes major economic losses for the English pig industry and severity of clinical signs and economic impact vary considerably between affected farms. We present here a novel approach to quantify severity of PMWS based on morbidity and mortality data and presence of porcine circovirus type 2 (PCV2...

The incidence of melanoma continues to increase in many countries, and primary prevention of melanoma includes avoidance of sunburn as well as adequate sun protection behavior. The aim of this study was to examine the prevalence of self-reported sun protection behaviors and sunburn in users of the Internet, and to identify the demographic, clinical...

Increased number of melanocytic nevi is a potent melanoma risk factor. We have carried out a large population-based case-control study to explore the environmental and genetic determinants of nevi and the relationship with melanoma risk. We report nevus phenotype in relation to differing patterns of sun exposure, inherited variation at loci shown i...

Cutaneous melanoma continues to increase in incidence in many countries, and intentional tanning is a risk factor for melanoma. The aim of this study was to understand how melanoma risk factors, perceived threat and preferences for a suntan relate to intentional tanning. Self-report data were collected on behalf of GenoMEL (www.genomel.org) from th...

We report an investigation of gene dosage at 9p21.3 and mutations in BRAF and NRAS, as predictors of relapse and histological markers of poor melanoma prognosis. Formalin-fixed primary melanomas from 74 relapsed and 42 nonrelapsed patients were sequenced for common BRAF and NRAS mutations (N = 71 results) and gene dosage at 9p21.3 including the gen...

A cohort study was carried out to test the hypothesis that higher vitamin D levels reduce the risk of relapse from melanoma. A pilot retrospective study of 271 patients with melanoma suggested that vitamin D may protect against recurrence of melanoma. We tested these findings in a survival analysis in a cohort of 872 patients recruited to the Leeds...

We have carried out melanoma case-control comparisons for six vitamin D receptor (VDR) gene single nucleotide polymorphisms (SNPs) and serum 25-hydroxyvitamin D(3) levels in order to investigate the role of vitamin D in melanoma susceptibility. There was no significant evidence of an association between any VDR SNP and risk in 1028 population-ascer...

Melanoma risk is related to sun exposure; we have investigated risk variation by tumour site and latitude. We performed a pooled analysis of 15 case-control studies (5700 melanoma cases and 7216 controls), correlating patterns of sun exposure, sunburn and solar keratoses (three studies) with melanoma risk. Pooled odds ratios (pORs) and 95% Bayesian...

A "divergent pathway" model for the development of cutaneous melanoma has been proposed. The model hypothesizes that melanomas occurring in people with a low tendency to develop nevi will, on average, arise more commonly on habitually sun-exposed body sites such as the head and neck. In contrast, people with an inherent propensity to develop nevi w...

An abnormal nevus phenotype is associated with an increased risk of melanoma. We report a pooled analysis conducted using individual nevus data from 15 case-control studies (5,421 melanoma cases and 6,966 controls). The aims were to quantify the risk better and to determine whether relative risk is varied by latitude. Bayesian unconditional logisti...

Dark spots in the fleece area are often associated with dark fibres in wool, which limits its competitiveness with other textile fibres. Field data from a sheep experiment in Uruguay revealed an excess number of zeros for dark spots. We compared the performance of four Poisson and zero-inflated Poisson (ZIP) models under four simulation scenarios....

A Bayesian procedure for analyzing longitudinal binary responses using a periodic cosine function was developed. It was assumed that, after adjustment for "seasonal" effects, the oscillation of the underlying latent variables for longitudinal binary responses was a stationary series. Based on this assumption, a single dimension sinusoidal analysis...

While natural selection might in some cases facilitate invasions into novel habitats, few direct measurements of selection response exist for invasive populations. This study examined selection response to changes in salinity using the copepod Eurytemora affinis. This copepod has invaded fresh water from saline habitats multiple times independently...

Genetic variation and covariation of liability to clinical mastitis in the course of first lactation in Norwegian Cattle (NRF) were investigated. The data consisted of 36,178 first-lactation cows with 354,506 clinical mastitis (absence=0 vs. presence=1) monthly records. A longitudinal binary data analysis was carried out using Bayesian threshold mo...

Test-day milk yield records (1752) of 451 first-lactation ewes in four flocks from Nebraska and Wisconsin were analyzed. Breeds included crosses among Dorset, Romanov, Targhee, Rideau Arcott, Polypay, Booroola Merino, Suffolk, Rambouillet, Finnsheep and East Friesian. The objective was to investigate genetic variation of features of lactation curve...