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Item VEGF-A cis-located SNPs on human chromosome 6 associated with VEGF-A plasma levels and survival in a coronary disease cohort(BioMed Central Ltd, 2025-12) Meza-Alvarado JC; Pilbrow AP; Frampton CM; Cameron VA; Richards AM; Troughton RW; Doughty RN; Page RA; Mallard B; Bromhead C; Palmer BRBackground: Cardiovascular disease (CVD) is the leading cause of death worldwide. Risk stratification of CVD patients may be improved by predictive biomarkers, including genetic markers. Elevated circulating vascular endothelial growth factor A (VEGF-A) levels have been linked to CVD development. We explored whether single nucleotide polymorphisms (SNPs) at the VEGFA locus on human chromosome 6 were associated with VEGF-A levels and clinical outcomes in established CVD. VEGF-A levels were compared between coronary heart disease patients and heart healthy controls. Methods: Imputed genotypes of 30 SNPs from the VEGFA region for 1935 patients from the Coronary Disease Cohort Study (CDCS) and 1183 individuals from the Canterbury Healthy Volunteers Study (HVOL) were analysed for associations with cardiometabolic parameters. Association with clinical endpoints was assessed using Kaplan-Meier analysis and multivariate regression models. To validate the findings from imputed data, DNA samples of 2027 CDCS patients and 227 HVOL participants were manually genotyped for variants rs6921438 and rs7767396. Baseline plasma VEGF-A assayed by ELISA in 227 HVOL participants was compared with levels in 549 CDCS patients. Results: Manual genotyping showed rs6921438 AA and rs7767396 GG genotype groups had lower VEGF-A levels at baseline (CDCS: rs6921438 AA (27.7 pg/mL), AG (43.3 pg/mL), GG (63.2 pg/mL), p = 4.49 × 10− 22; rs7767396: GG (27.4 pg/mL), AG (42.8 pg/mL), AA (61.5 pg/mL) p = 3.47 × 10− 21; HVOL rs6921438 AA (12.8 pg/mL), GA (19.9 pg/mL), GG (26.4 pg/mL) p = 0.021; rs7767396 GG (12.6 pg/mL), AG (19.6 pg/mL), AA (25.9 pg/mL) p = 0.029). In the CDCS cohort rs6921438 AA was associated with increased risk of all-cause death (p = 0.03); non ST-elevated myocardial infarction (NSTEMI, p = 0.0003), heart failure (HF, p = 0.035) and major adverse cardiovascular events (p = 0.032); rs7767396 GG was associated with increased NSTEMI (p = 0.001) and HF (p = 0.023) risk; rs6921438 AA (Hazard Ratio (HR) = 6.55 p = 0.017), rs7767396 GG (HR = 0.149, p = 0.017) and VEGF-A (HR = 2.55, p = 0.018) were independent HF admission risk predictors. Conclusions: Variants rs6921438 and rs7767396 are associated with plasma VEGF-A levels. Both SNPs and VEGF-A may be useful in prognosis for HF after acute coronary events.Item Bedside EEG predicts longitudinal behavioural changes in disorders of consciousness(Elsevier Inc, 2020) Bareham CA; Roberts N; Allanson J; Hutchinson PJA; Pickard JD; Menon DK; Chennu SProviding an accurate prognosis for prolonged disorder of consciousness (pDOC) patients remains a clinical challenge. Large cross-sectional studies have demonstrated the diagnostic and prognostic value of functional brain networks measured using high-density electroencephalography (hdEEG). Nonetheless, the prognostic value of these neural measures has yet to be assessed by longitudinal follow-up. We address this gap by assessing the utility of hdEEG to prognosticate long-term behavioural outcome, employing longitudinal data collected from a cohort of patients assessed systematically with resting hdEEG and the Coma Recovery Scale-Revised (CRS-R) at the bedside over a period of two years. We used canonical correlation analysis to relate clinical (including CRS-R scores combined with demographic variables) and hdEEG variables to each other. This analysis revealed that the patient’s age, and the hdEEG theta band power and alpha band connectivity, contributed most significantly to the relationship between hdEEG and clinical variables. Further, we found that hdEEG measures recorded at the time of assessment augmented clinical measures in predicting CRS-R scores at the next assessment. Moreover, the rate of hdEEG change not only predicted later changes in CRS-R scores, but also outperformed clinical measures in terms of prognostic power. Together, these findings suggest that improvements in functional brain networks precede changes in behavioural awareness in pDOC. We demonstrate here that bedside hdEEG assessments conducted at specialist nursing homes are feasible, have clinical utility, and can complement clinical knowledge and systematic behavioural assessments to inform prognosis and care.Item Downer cows: a reanalysis of an old data set.(Taylor and Francis Group on behalf of the New Zealand Veterinary Association, 2023-01-23) Lawrence KE; Clark RG; Henderson HV; Govindaraju K; Balcomb CAIMS: To compare the performance of two predictive models for the survival of downer cows. METHODS: The first model had been developed in 1987 using a dataset containing missing values, while the second, new model was developed on the same dataset but using modern data imputation and analytical methods. Missing data were imputed using multiple imputation by chained equations and a logistic regression model fitted to the imputed data, with survival or not as the outcome variable. The predictive ability of the model built on the imputed data was contrasted with the original prognostic model by testing them both on a second smaller but complete data set, collected contemporaneously with the development of the original model but from a different region of New Zealand. Sensitivity, specificity, accuracy, and cut point for the two models were calculated. RESULTS: The original 1987 model had a slightly higher accuracy than that of the new one with a sensitivity of 0.85 (95% CI = 0.72-0.94) and a specificity of 0.82 (95% CI = 0.7-0.91), using a cut point for the probability of survival = 0.313. CONCLUSIONS: The original prognostic formula published by Clark et al. in 1987 performed as well as a modern model built on an imputed data set. CLINICAL RELEVANCE: The use of a prognostic test based on the Clark model should remain an important part of the clinical examination of downer cows by New Zealand veterinarians. Abbreviations: AUC: Area under the curve; AST: Aspartate transaminase activity; CK: Creatine phosphokinase activity; GAM: Generalised additive model; NSAID: Non-steroidal-anti-inflammatory drugs; PCV: Packed cell volume.Item Prognostic significance of tumour-associated inflammation related markers in canine mammary gland tumours : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Veterniary Science at Massey University, Manawatū, New Zealand(Massey University, 2020) Ariyarathna, HarshaCanine mammary gland tumours (CMGTs) are a major cause of illness and premature death in female dogs, especially in countries like Sri Lanka where early de-sexing is not a routine veterinary practice. Therefore, there is a need for prognostic markers which can better predict the behaviour of a CMGT. In human breast cancers (HBCs), some markers of tumour-associated inflammation (TAI) have been shown to better predict prognosis than many conventional prognostic markers. This thesis investigated whether TAI prognostic markers adopted from human breast cancers are similarly prognostic for CMGTs. The prognostic markers investigated in this thesis included tumour stromal mast cell density determined by toluidine blue staining, gene expression of chemokines: CCL5, CXCL12, CXCL10, and chemokine receptors: CXCR3, CXCR4, CXCR7, CCR4, CCR9 and gene expression and immunostaining of two immune checkpoint molecules: programme death ligand-1 (PD-L1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) . Similar to HBCs, all markers except CXCL10 and CCR4 were prognostic of the disease outcome determined by disease-specific survival times of the dogs with mammary neoplasms. Of them, stromal mast cell density, CCL5 gene expression and PD-L1 immunostaining were prognostic independent of tumour size, tumour histological grade, and lympho-vascular invasion observed in histological sections. In conclusion, this thesis identified that similar to HBCs, TAI related prognostic markers are useful to better predict the behaviour of CMGTs while stromal mast cell density has the potential to be adopted for routine laboratory prognostic determination. In addition to identification of prognostic markers, surveys of CMGTs in Sri Lanka and New Zealand conducted for sample collection gathered large amounts of information that allowed a comparison of CMGTs between the two countries. These studies allowed a determination of the characteristics of dogs with CMGTs, as well as allowing histological characterisation of the tumours within the two countries.Item Understanding the prognosis and progression of soft tissue sarcoma in the dog : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy at Massey University, Manawatū, New Zealand(Massey University, 2020) Bray, JonathanSoft tissue sarcoma (STS) are tumours derived from tissues of mesenchymal origin. Local recurrence of the tumour following surgical resection is the characteristic challenge in the management of STS. There are currently no prognostic tests that can reliably predict which tumours have a higher or lower risk of recurrence. The aim of the studies contained in this thesis was to investigate aspects of STS biology to identify new prognostic markers. A large archive of STS was established with patient outcomes determined by questionnaire. Tissue was subsequently analysed using immunohistochemistry and reverse transcriptase-polymerase chain reaction to understand the role of two molecules – vascular endothelial growth factor (VEGF) and decorin – in influencing tumour behaviour. This study revealed that when the tissue stroma surrounding the tumour cells had a strong immunostaining intensity for decorin, the risk of tumour-related death was significantly reduced. In addition, STS with a high immunostaining for VEGF were more than 7 times more likely to recur, and 5 times more likely to cause the death of the dog. When the immunostaining characteristics for VEGF and decorin were combined with other patient and tumour features into a predictive algorithm called a nomogram, it was possible to determine, with almost 100% accuracy, which dogs would remain disease-free 3 years after surgery. The importance of VEGF in the progression of tumour growth was subsequently demonstrated by treating dogs with haemangiosarcoma (HSA) – a mesenchymal tumour with many characteristics similar to STS – with thalidomide. Thalidomide is a potent antagonist of VEGF, but also has a number of other modulating influences on the tumour microenvironment. Dogs treated with thalidomide survived significantly longer than dogs that did not receive this drug, suggesting that thalidomide can slow the ability for residual microscopic tumour cells to develop into a grossly visible, and life-threatening tumour. An analysis of metastatic lesions that developed in dogs treated with thalidomide revealed that immunostaining for VEGF was significantly reduced. This suggests that thalidomide may be a useful adjuvant therapy for dogs with STS that are considered to be at high risk of recurrence after surgery, as determined by their VEGF immunostaining intensity.Item Clinical parameters at time of admission as prognostic indicators in cats presented for trauma to an emergency centre in New Zealand: a retrospective analysis.(2022-12) Fitzgerald WR; Cave NJ; Yozova IDOBJECTIVES: The aims of this study were to describe the clinical features of cats presented for trauma in a first-opinion and referral teaching hospital in New Zealand, and to determine the relationship between those features and outcome. METHODS: The electronic medical records of cats presented for trauma to the Massey University Pet Emergency Centre between September 2013 and January 2019 were examined, from which the signalment, clinical parameters and patient outcomes were extracted. Cases were assigned an Animal Trauma Triage (ATT) score and Modified Glasgow Coma Scale (MGCS) score. Variables were selected for inclusion in a logistic regression model to predict survival, and backward elimination was used to find the minimal significant model. RESULTS: In total, 530 cats met the inclusion criteria. The cause of injury was not known in the majority of cases (38.0%). The most common location of injury was the hindlimbs/pelvis/tail (n = 247; 41%), and skin lacerations/abrasions were the most common specific injury. Multivariate analysis revealed altered mentation (odds ratio [OR] 0.31, P = 0.029), hypothermia (rectal temperature <37.8°C [<100.04°F]; OR 0.45, P = 0.015) and an ATT score ⩾5 (OR 0.13, P <0.001) to be statistically significantly associated with mortality. CONCLUSIONS AND RELEVANCE: Altered mentation and hypothermia are easily measurable perfusion parameter abnormalities associated with mortality in cats presenting with trauma. The ATT score appears to be an accurate prognostic indicator in cats presenting with trauma in New Zealand. These results highlight the importance of incorporating a hands-on triage examination in each cat that presents as an emergency after trauma.