University General - Research Publications
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Mid-infrared Magnetic Mirror Based on a Hybrid Metal/Dielectric Metasurface
We propose a hybrid metal/dielectric metasurface that functions as a mid-infrared magnetic mirror. It consists amorphous silicon cuboids on gold. The physical mechanism is explained by image theory. Measured reflection spectra agree with simulations.
Systematic review of pharmacogenomics and adverse drug reactions in paediatric oncology patients.
Many paediatric patients with cancer experience significant chemotherapy side effects. Predisposition to drug reactions is governed by single nucleotide polymorphisms (SNPs). We performed a systematic review of the literature from 2006 through 2016. Outcomes of interest included patient characteristics, cancer type drug of interest, genes investigated, toxicity identified and genetic polymorphisms implicated. The primary toxicities studied were neurotoxicity cardiotoxicity, osteonecrosis, and thromboembolism and hypersensitivity reactions. The retrieved studies were grouped according to toxicity reported and SNP associations. This review highlights the discoveries to date in pharmacogenomics and paediatric oncology along with highlighting some of the important limitations in the area.
Atopy in people aged 40 years and over: Relation to airflow limitation.
BACKGROUND: Previous studies have reached conflicting conclusions about the role of atopy as a risk factor for COPD. In part, this is attributable to variation in the definitions of airflow limitation and the treatment of people with asthma. OBJECTIVE: To establish whether there is any independent association between atopy and post-bronchodilator airflow limitation in the general population aged 40 years and over. METHODS: A cross-sectional survey was conducted in a general population sample of 2415 people aged 40 years and over in Australia. A history of ever being diagnosed with asthma was elicited by questionnaire. Atopy was defined as any skin prick test weal to common aeroallergens ≥4 mm. Airflow limitation was defined as post-bronchodilator spirometric (FEV1 /FVC) ratio <lower limit of normal. Analyses were adjusted for potential confounding due to age, sex, smoking, race and socio-economic status. RESULTS: The prevalence of atopy, ever diagnosed asthma and post-bronchodilator airflow obstruction was 44.8%, 19.3% and 7.5%, respectively. In the population as a whole, atopy was associated with lower FEV₁ (adjusted difference -0.068L, 95% confidence interval (CI) -0.104 to -0.032), FVC (adj. difference -0.043L, 95% CI -0.086 to -0.0009) and post-bronchodilator FEV₁/FVC ratio (adj. difference -0.011, 95% CI -0.017 to -0.0055). The effect of atopy on lung function was no longer apparent when participants who reported ever diagnosed asthma were excluded (FEV₁ -0.011L, [95% CI -0.05 to 0.028L], FVC -0.012L [95% CI -0.060 to 0.036] and FEV₁/FVC ratio -0.0012 [95% CI -0.0072 to 0.0047L]). CONCLUSION AND CLINICAL RELEVANCE: The apparent association between atopy and post-bronchodilator airflow limitation in the general population appears to be explained by the association between atopy and having ever diagnosed asthma and the effect of asthma on lung function.
Short-term (48hours) intravenous serelaxin infusion has no effect on myogenic tone or vascular remodeling in rat mesenteric arteries
BACKGROUND: Short-term IV sRLX (recombinant human relaxin-2) infusion enhances endothelium-dependent relaxation in mesenteric arteries. This is initially underpinned by increased NO followed by a transition to prostacyclin. The effects of short-term IV sRLX treatment on pressure-induced myogenic tone and vascular remodeling in these arteries are unknown. Therefore, we investigated the effects of sRLX infusion on pressure-induced myogenic tone and passive mechanical wall properties in mesenteric arteries. METHODS: Mesenteric artery myogenic tone and passive mechanics were examined after 48-hours and 10-days infusion of sRLX. Potential mechanisms of action were assessed by pressure myography, qPCR, and Western blot analysis. RESULTS: Neither 48-hours nor 10-days sRLX treatment had significant effects on myogenic tone, passive arterial wall stiffness, volume compliance, or axial lengthening. However, in 48-hours sRLX -treated rats, incubation with the NO synthase blocker L-NAME significantly increased myogenic tone (P<.05 vs placebo), demonstrating an increased contribution of NO to the regulation of myogenic tone. eNOS dimerization, but not phosphorylation, was significantly upregulated in the arteries of sRLX -treated rats. CONCLUSION: In mesenteric arteries, 48-hours sRLX treatment upregulates the role of NO in the regulation of myogenic tone by enhancing eNOS dimerization, without altering overall myogenic tone or vascular remodeling.
Dietary analysis and nutritional counselling for caries prevention in dental practise: a pilot study
BACKGROUND: Dental practitioners agree that dietary counselling is essential for caries prevention; however, they provide advice infrequently due to a lack of confidence and competence. This study aimed to improve practises through an online training module exploring the use of a brief counselling method, and a diet assessment of caries risk form. METHODS: Dental practitioners (N = 41) completed a survey on current practises and confidence in providing dietary advice, followed by an online training module. Ten practitioners were involved in recruiting patients, eliciting a diet assessment of caries risk, and using brief counselling techniques with these patients. Patients were followed up at 6 months for a risk assessment review. Dental practitioners also completed a 6-month follow-up survey exploring changes in confidence and perceived barriers. RESULTS: Dental hygienists' confidence improved significantly following the intervention (P < 0.025). Patients showed a significant reduction in high-risk behaviour pertaining to quantity and timing of sugar intake, and significant trends in improvement of behaviours relating to frequency, exposure time and drinking style (P < 0.05). CONCLUSIONS: It appears that a simple online learning module can improve hygienists' confidence in dietary advice provision, and have a positive impact on patient behaviour change, within a relatively short time-frame.
Younger age is a risk factor for regrowth and recurrence of nonfunctioning pituitary macroadenomas: Results from a single Australian centre.
OBJECTIVE: The natural history of nonfunctioning pituitary macroadenomas (NFPMA) after surgical resection is variable, with guidelines unable to define the duration of radiological follow-up. In this first Australian series, we identify risk factors for regrowth/recurrence of NFPMA to assist with guiding recommendations for long-term follow-up. DESIGN: Retrospective analysis of all radiotherapy-naïve cases with NFPMA resected between 1995 and 2013. PATIENTS: One hundred and twenty-three cases had both ≥2 postoperative scans and ≥12-month follow-up. MEASUREMENTS: Regrowth was defined as any sustained increase in diameter of residual adenoma or recurrence as any new adenoma occurring post complete resection on serial pituitary MRI. RESULTS: Median follow-up time was 48 months (interquartile range [IQR]: 31-86). Overall regrowth/recurrence occurred in 29% (36/123). Regrowth occurred in 40% (30/76) at a median time of 44.5 months (IQR 22-80) compared to recurrence of 12.5% (6/48; P=.003), occurring at a median time of 48 months (IQR 12-96; P=.7). Further treatment was required in 66.7% and 56.7%, respectively (=1.0). Risk factors for regrowth/recurrence by multivariate analysis were presence of residual disease and younger age at presentation. The longest time for regrowth was 168 months (14 years) and recurrence 156 months (13 years). CONCLUSIONS: Presence of postoperative residual adenoma and younger age at presentation are the main predictors of regrowth/recurrence in NFPMA. Long-term serial imaging is required to detect regrowth and recurrence in younger patients and those with residual disease. Most regrowth/recurrences will occur within 10 years of follow-up.
Age at onset and persistence of eczema are related to subsequent risk of asthma and hay fever from birth to 18 years of age
BACKGROUND: Few studies have simultaneously addressed the importance of age of onset and persistence of eczema for the subsequent development of asthma and hay fever, particularly into early adulthood. METHODS: A high-risk birth cohort was recruited comprising 620 infants, who were then followed up frequently until 2 years of age, annually from age 3 to 7, then at 12 and 18 years, to document any episodes of eczema, current asthma, and hay fever. The generalized estimation equation technique was used to examine asthma and hay fever outcomes at 6 (n = 325), 12 (n = 248) and 18 (n = 240) years, when there was consistency of associations across the follow-ups. RESULTS: Very early-onset persistent (onset <6 months, still present from 2 to 5 years) eczema was related to current asthma (adjusted OR = 3.2 [95% CI = 1.7-6.1]), as was very early-onset remitting eczema (onset <6 months but not present from 2-5 years, OR = 2.7, 95% CI = 1.0-7.2) and early-onset persistent eczema (onset from 6-24 months, OR = 2.3, 95% CI = 1.2-4.7). Late-onset eczema (commenced from 2-5 years) was associated with increased risk of asthma at 12 years (OR = 3.0, 95% CI=1.1-8.2) but not at age 6 years. Only very early-onset persistent eczema was associated with increased risk of hay fever (aOR = 2.4, 95% CI = 1.4-4.1). CONCLUSION AND CLINICAL RELEVANCE: Eczema which commences in early infancy and persists into toddler years is strongly associated with asthma, and to a lesser extent hay fever, in high-risk children. If these associations are causal, prevention of early-life eczema might reduce the risk of respiratory allergy.
Can additional N fertiliser ameliorate the elevated CO2-induced depression in grain and tissue N concentrations of wheat on a high soil N background?
Elevated COâ stimulates crop yields but leads to lower tissue and grain nitrogen concentrations [N], raising concerns about grain quality in cereals. To test whether N fertiliser application above optimum growth requirements can alleviate the decline in tissue [N], wheat was grown in a Free Air COâ Enrichment facility in a lowâ rainfall cropping system on high soil N. Crops were grown with and without addition of 50â 60Â kg N/ha in 12 growing environments created by supplemental irrigation and two sowing dates over 3Â years. Elevated COâ increased yield and biomass (on average by 25%) and decreased biomass [N] (3%â 9%) and grain [N] (5%). Nitrogen uptake was greater (20%) in crops grown under elevated COâ . Additional N supply had no effect on yield and biomass, confirming high soil N. Small increases in [N] with N addition were insufficient to offset declines in grain [N] under elevated COâ . Instead, N application increased the [N] in straw and decreased N harvest index. The results suggest that conventional addition of N does not mitigate grain [N] depression under elevated COâ , and lend support to hypotheses that link decreases in crop [N] with biochemical limitations rather than N supply.
High serum vitamin D level correlates with better prognostic indicators in primary melanoma: A pilot study
BACKGROUND/OBJECTIVES: Sunlight is a major risk factor for cutaneous melanoma. However, its interaction with melanoma is complex. In particular, vitamin D is a UVB-derived hormone that has been shown to have anti-cancer effects. In this retrospective pilot study we sought to determine an association between the clinicopathological features of melanoma and the patients' corresponding serum vitamin D level. METHODS: In total, 109 primary melanomas diagnosed between 2001 and 2013 were retrospectively identified from our institutional database with a corresponding 25-hydroxyvitamin D3 level estimated within 6 months of diagnosis. Tumour, clinical (age, sex, tumour location) and pathological (thickness, mitosis, ulceration, Clark level, subtype, metastatic status) parameters were correlated with vitamin D. For statistical analysis, an unpaired Student's t-test and anova was used for categorical variables, and Spearman's correlation for continuous variables. RESULTS: Vitamin D level was inversely associated with Breslow thickness as a dichotomous, categorical and continuous variable. The association remained significant when controlled for patient's age and sex (P = 0.026). Vitamin D was higher in non-ulcerated tumours compared with ulcerated tumours (P = 0.006) and in tumours with mitotic rate <1/mm2 compared with ≥1/mm2 (P = 0.036). A significant association was found between vitamin D level and tumour histological subtype (P = 0.019). On subgroup analysis, significant associations were found between superficial spreading melanoma (SSM) and nodular melanoma (P = 0.026), and SSM and acral lentiginous melanoma (P = 0.007). CONCLUSION: A high vitamin D status may benefit prognosis in patients diagnosed with primary melanoma. A prospective cohort analysis with a large sample and controlled for other vitamin D confounders would validate these findings.
Low-dose rituximab and concurrent adjuvant therapy for pemphigus: Protocol and single-centre long-term review of nine patients
Pemphigus is an autoimmune B-cell mediated blistering disease associated with significant morbidity and mortality. Rituximab has proven effective for the treatment of steroid-refractory pemphigus, although there is controversy over the optimum dosing protocol. Additionally, effective disease control often requires long-term immunosuppression, even in disease-free periods. We present a case series of a single-centre long-term follow up of nine patients with pemphigus, treated with two 500-mg doses of rituximab separated by 14 days along with concurrent adjuvant therapy. In all these patients, low-dose rituximab resulted in B-cell depletion, along with a reduction in blistering disease. Three of these patients required repeat dosing cycles due to either relapsed disease or incomplete disease control following the first dosing cycle, and have remained disease free up to 154 weeks thus far. Six patients developed minor infections during the course of their treatment, but no major complications were observed.
Breast milk polyunsaturated fatty acids: associations with adolescent allergic disease and lung function
BACKGROUND: It has been hypothesized that n-3 PUFA in breast milk may assist immune and lung development. There are very limited data on possible long-term effects on allergic disease and lung function. The aim was to investigate associations of n-3 and n-6 PUFA levels in colostrum and breast milk with allergic disease and lung function at ages 12 and 18 years. METHODS: Polyunsaturated fatty acids were measured in 194 colostrum samples and in 118 three-month expressed breast milk samples from mothers of children enrolled in the Melbourne Atopy Cohort (MACS) Study, a high-risk birth cohort study. Associations with allergic diseases, skin prick tests and lung function assessed at 12 and 18 years were estimated using multivariable regression. RESULTS: Higher levels of n-3 but not n-6 PUFAs in colostrum were associated with a trend towards increased odds of allergic diseases, with strong associations observed for allergic rhinitis at 12 (OR = 5.69[95% CI: 1.83,17.60] per weight%) and 18 years (4.43[1.46,13.39]) and eczema at 18 years (9.89[1.44, 68.49]). Higher levels of colostrum n-3 PUFAs were associated with reduced sensitization (3.37[1.18, 9.6]), mean FEV1 (-166 ml [-332, -1]) and FEV1 /FVC ratio (-4.6%, [-8.1, -1.1]) at 12 years. CONCLUSION: Higher levels of colostrum n-3 PUFAs were associated with increased risks of allergic rhinitis and eczema up to 18 years, and sensitization and reduced lung function at 12 years. As residual confounding may have caused these associations, they should be replicated, but these results could indicate that strategies that increase maternal n-3 PUFA intake may not aid in allergic disease prevention.
Beyond the Storm: Comparison of Clinical Factors, Arrhythmogenic Substrate, and Catheter Ablation Outcomes in Structural Heart Disease Patients With versus Those Without a History of Ventricular Tachycardia Storm.
AIMS: Catheter ablation can be lifesaving in ventricular tachycardia (VT) storm, but the underlying substrate in patients with storm is not well characterized. We sought to compare the clinical factors, substrate, and outcomes differences in patients with sustained monomorphic VT who present for catheter ablation with VT storm versus those with a nonstorm presentation. METHODS: Consecutive ischemic (ICM; n = 554) or nonischemic cardiomyopathy patients (NICM; n = 369) with a storm versus nonstorm presentation were studied (ICM storm 186; NICM storm 101). RESULTS: In ICM, storm compared with nonstorm patients had significantly lower left ventricular (LV) ejection fraction (EF), greater number of antiarrhythmic drug (AAD) failures, slower VTs, greater number of scarred LV segments, higher incidence of anterior, septal, and apical endocardial LV scar (all P < 0.05). However, outcomes in follow-up were similar (12-month ventricular arrhythmia [VA]-free survival: 51% vs. 52%, P = 0.6; survival free of death/transplant 75% vs. 87%, P = 0.7). In addition to the above differences, NICM storm patients were also older; however, the extent and distribution of scar was similar except for a higher incidence of lateral endocardial scar in storm patients (P = 0.05). VA-free survival (36% vs. 47%, P = 0.004) and survival free of death/transplant, however, were worse in NICM storm than nonstorm patients (72% vs. 88%, P = 0.001). NICM storm patients had worse VA-free survival than ICM storm patients. CONCLUSION: There are differences in clinical factors and scar patterns in patients undergoing VT ablation who present with VT storm versus those with a nonstorm presentation. Clinical outcomes are worse in NICM storm patients.
Does serelaxin treatment alter passive mechanical wall properties in small resistance arteries?
The peptide hormone relaxin is recognized for its connective tissue remodeling actions in the reproductive tract during pregnancy and parturition, but it also has vascular remodeling actions independent of pregnancy. Recombinant human relaxin (serelaxin) treatment in male and non-pregnant female rodents enhances passive arterial compliance in the renal vasculature. This review focuses on serelaxin's actions on passive mechanical wall properties in small arteries and highlights the diversity of responses to serelaxin treatment in rodents. Different experimental approaches (duration of serelaxin treatment, rat strain, age) and animal models of disease (obesity, hypertension) will be considered. Most studies in young rodents demonstrate that serelaxin treatment fails to alter passive compliance in resistance-size arteries (mesenteric and femoral arteries and cerebral parenchymal arterioles), suggesting that serelaxin's beneficial effects are minimal in healthy animals. Short-term serelaxin treatment (5d) in aged, obese, and spontaneously hypertensive rats (SHRs) is largely without effect on passive mechanical wall properties. However, a longer duration of serelaxin treatment in SHRs (14d) enhances passive compliance in large muscular arteries as well as resistance-size arteries. In conclusion, serelaxin is capable of vascular remodeling. Its actions are vascular bed-dependent, more prominent in disease, and likely requires a longer duration of treatment to be effective.
Sites With Small Impedance Decrease During Catheter Ablation for Atrial Fibrillation Are Associated With Recovery of Pulmonary Vein Conduction
OBJECTIVE: To correlate impedance decrease during atrial fibrillation (AF) ablation with lesion durability and PV conduction recovery demonstrated during redo procedures. BACKGROUND: Markers of successful ablation beyond acute conduction block are needed to improve durability of pulmonary vein (PV) isolation (PVI). Local impedance decrease resulting from ablation is a real-time marker of tissue heating and is correlated with lesion creation. METHODS: Impedance changes associated with point-by-point radiofrequency ablation in the PV antra were recorded during 167 consecutive first-time AF ablations. During clinically indicated redo procedures, sites of recovered PV conduction were identified, and were correlated with the impedance change achieved during ablation at these locations during the initial procedure. RESULTS: Redo procedures were performed in 28 patients, in whom 19 sites of recovered PV conduction were documented. Most sites of PV reconnection (58%) occurred along the posterior PV antra. Ablation resulting in impedance decrease <10 ohms during the initial procedure was present in 89% (17/19) of sites with conduction recovery. Regions with adjacent ablation resulting in impedance decrease <10 ohms were associated with a higher rate of conduction recovery (37% vs. 1.5%, P < 0.001). Likewise, patients with PV conduction recovery demonstrated during redo procedure (Group 1) had larger regions where ablation resulted in <10 ohm impedance decrease than patients without PV conduction recovery (Group 2) (21.9 ± 15.5 mm vs. 11.5 ± 2.1 mm, P < 0.01). CONCLUSION: Recovered PV conduction occurs predominantly in regions where adjacent ablation applications result in impedance decreases <10 ohms. Impedance-guided ablation strategies may improve durability of PVI.
Vascular actions of relaxin: nitric oxide and beyond
The peptide hormone relaxin regulates the essential maternal haemodynamic adaptations in early pregnancy through direct actions on the renal and systemic vasculature. These vascular actions of relaxin occur mainly through endothelium-derived NO-mediated vasodilator pathways and improvements in arterial compliance in small resistance-size arteries. This work catalysed a plethora of studies which revealed quite heterogeneous responses across the different regions of the vasculature, and also uncovered NO-independent mechanisms of relaxin action. In this review, we first describe the role of endogenous relaxin in maintaining normal vascular function, largely referring to work in pregnant and male relaxin-deficient animals. We then discuss the diversity of mechanisms mediating relaxin action in different vascular beds, including the involvement of prostanoids, VEGF, endothelium-derived hyperpolarisation and antioxidant activity in addition to the classic NO-mediated vasodilatory pathway. We conclude the review with current perspectives on the vascular remodelling capabilities of relaxin. LINKED ARTICLES: This article is part of a themed section on Recent Progress in the Understanding of Relaxin Family Peptides and their Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.10/issuetoc.
Depression and anger in fathers of unsettled infants: A community cohort study
AIM: To examine the relationship between unsettled infant behaviour and fathers' depressive symptoms, cognitions surrounding infant sleep (anger, doubt), and personal sleep, in a community cohort. METHODS: Data were collected from 102 fathers of healthy infants at 4 weeks, 4 months and 6 months of age. Measures included father report of infant sleep and crying problems, depressive symptoms, cognitions about infant sleep and own sleep quality and quantity. Data were analysed using adjusted regression models. RESULTS: Sleep problems at 4 months of age were associated with increased depressive symptoms (adjusted mean difference 2.64 (1.27-4.00)), doubt (adjusted mean difference 1.82 (0.40-3.25)), anger (adjusted mean difference 1.86 (0.51-3.20)), poor personal sleep quantity (adjusted odds ratio (OR) 0.21; 95% confidence interval (CI) 0.09-0.51) and quality (adjusted OR 0.20; 95% CI 0.08-0.51); and at 6 months of age, with increased depressive symptoms (adjusted mean difference 2.56 (1.28-3.84)), anger (adjusted mean difference 1.63 (0.40-2.87)), poor personal sleep quantity (adjusted OR 0.14; 95% CI 0.05-0.38) and quality (adjusted OR 0.28; 95% CI 0.11-0.72). Infant cry problems at 4 months were associated with increased anger (adjusted mean difference 1.98 (0.60-3.36)) and doubt (adjusted mean difference 1.55 (0.05-3.05)); and at 6 months, with increased depressive symptoms (adjusted mean difference 3.04 (1.59-4.69)), anger (adjusted mean difference 2.73 (1.29-4.17)) and less personal sleep (adjusted OR 0.22; 95% CI 0.07-0.71). CONCLUSION: Fathers of unsettled infants reported greater anger towards their infant and increased depressive symptoms by 4 months infant age, with these symptoms persisting 2 months later. Evidence-based interventions are needed for these fathers.
Human glandular organoid formation in murine engineering chambers after collagenase digestion and flow cytometry isolation of normal human breast tissue single cells
Women with high mammographic density (MD) are at increased risk of breast cancer (BC) after adjustment for age and body mass index. We have developed a murine biochamber model in which both high MD (HMD) and low MD (LMD) tissue can be propagated. Here, we tested whether cells isolated by collagenase digestion and fluorescence-activated cell sorting (FACS) from normal breast can be reconstituted in our biochamber model, which would allow cell-specific manipulations to be tested. Fresh breast tissue was collected from women (n = 7) undergoing prophylactic mastectomy. The tissue underwent collagenase digestion overnight and, in some cases, additional FACS enrichment to obtain mature epithelial, luminal progenitor, mammary stem, and stromal cells. Cells were then transferred bilaterally into biochambers in SCID mice (n = 5-7) and incubated for 6 weeks, before harvesting for histological analyses, and immunohistochemical staining for cytokeratins (CK), vimentin, Ki-67, murine macrophages, and Cleaved Caspase-3. Biochambers inoculated with single cells after collagenase digestion or with flow cytometry contained glandular structures of human origin (human vimentin-positive), which expressed CK-14 and pan-CK, and were proliferating (Ki-67-positive). Glandular structures from the digested tissues were smaller than those in chambers seeded with finely chopped intact mammary tissue. Mouse macrophage infiltration was higher in the chambers arising from digested tissues. Pooled single cells and FACS fractionated cells were viable in the murine biochambers and formed proliferating glandular organoids of human origin. This is among the first report to demonstrate the success of formed human glandular organoids from isolated primary mammary cells in the murine biochamber model.