Journal Articles

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    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 BR
    Background: 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.
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    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 S
    Providing 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.
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    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 C
    AIMS: 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.
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    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 ID
    OBJECTIVES: 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.
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    Plasma levels of soluble VEGF receptor isoforms, circulating pterins and VEGF system SNPs as prognostic biomarkers in patients with acute coronary syndromes
    (BioMed Central Ltd, 15/08/2018) Marks ECA; Wilkinson TM; Frampton CM; Skelton L; Pilbrow AP; Yandle TG; Pemberton CJ; Doughty RN; Whalley GA; Ellis CJ; Troughton RW; Owen MC; Pattinson NR; Cameron VA; Richards AM; Gieseg SP; Palmer BR
    BACKGROUND: Development of collateral circulation in coronary artery disease is cardio-protective. A key process in forming new blood vessels is attraction to occluded arteries of monocytes with their subsequent activation as macrophages. In patients from a prospectively recruited post-acute coronary syndromes cohort we investigated the prognostic performance of three products of activated macrophages, soluble vascular endothelial growth factor (VEGF) receptors (sFlt-1 and sKDR) and pterins, alongside genetic variants in VEGF receptor genes, VEGFR-1 and VEGFR-2. METHODS: Baseline levels of sFlt-1 (VEGFR1), sKDR (VEGFR2) and pterins were measured in plasma samples from subgroups (n = 513; 211; 144, respectively) of the Coronary Disease Cohort Study (CDCS, n = 2067). DNA samples from the cohort were genotyped for polymorphisms from the VEGFR-1 gene SNPs (rs748252 n = 2027, rs9513070 n = 2048) and VEGFR-2 gene SNPs (rs2071559 n = 2050, rs2305948 n = 2066, rs1870377 n = 2042). RESULTS: At baseline, levels of sFlt-1 were significantly correlated with age, alcohol consumption, NTproBNP, BNP and other covariates relevant to cardiovascular pathophysiology. Total neopterin levels were associated with alcohol consumption at baseline. 7,8 dihydroneopterin was associated with BMI. The A allele of VEGFR-2 variant rs1870377 was associated with higher plasma sFlt-1 and lower levels of sKDR at baseline. Baseline plasma sFlt-1 was univariately associated with all cause mortality with (p < 0.001) and in a Cox's proportional hazards regression model sFlt-1 and pterins were both associated with mortality independent of established predictors (p < 0.027). CONCLUSIONS: sFlt-1 and pterins may have potential as prognostic biomarkers in acute coronary syndromes patients. Genetic markers from VEGF system genes warrant further investigation as markers of levels of VEGF system components in these patients. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry. ACTRN12605000431628 . 16 September 2005, Retrospectively registered.