Medicine (Austin & Northern Health) - Research Publications
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ItemProlonged Eyelid Closure Episodes during Sleep Deprivation in Professional Drivers(AMER ACAD SLEEP MEDICINE, 2016)STUDY OBJECTIVES: Real life ocular measures of drowsiness use average blink duration, amplitude and velocity of eyelid movements to reflect drowsiness in drivers. However, averaged data may conceal the variability in duration of eyelid closure episodes, and more prolonged episodes that indicate higher levels of drowsiness. The current study aimed to describe the frequency and duration of prolonged eyelid closure episodes during acute sleep deprivation. METHODS: Twenty male professional drivers (mean age ± standard deviation = 41.9 ± 8.3 years) were recruited from the Transport Workers Union newsletter and newspaper advertisements in Melbourne, Australia. Each participant underwent 24 hours of sleep deprivation and completed a simulated driving task (AusEd), the Psychomotor Vigilance Task, and the Karolinska Sleepiness Scale. Eyelid closure episodes during the driving task were recorded and analyzed manually from digital video recordings. RESULTS: Eyelid closure episodes increased in frequency and duration with a median of zero s/h of eyelid closure after 3 h increasing to 34 s/h after 23 h awake. Eyelid closure episodes were short and infrequent from 3 to 14 h of wakefulness. After 17 h of sleep deprivation, longer and more frequent eyelid closure episodes began to occur. Episodes lasting from 7 seconds up to 18 seconds developed after 20 h of wakefulness. Length of eyelid closure episodes was moderately to highly correlated with the standard deviation of lateral lane position, braking reaction time, crashes, impaired vigilance, and subjective sleepiness. CONCLUSIONS: The frequency and duration of episodes of prolonged eyelid closure increases during acute sleep deprivation, with very prolonged episodes after 17 hours awake. Automated devices that assess drowsiness using averaged measures of eyelid closure episodes need to be able to detect prolonged eyelid closure episodes that occur during more severe sleep deprivation.
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ItemData on common variants associated with coronary artery disease/myocardial infarction in ethnic Arabs.(Elsevier BV, 2016-06)The data shows results acquired in a large cohort of 5668 ethnic Arabs involved in a common variants association study for coronary artery disease (CAD) and myocardial infarction (MI) using the Affymetrix Axiom Genotyping platform ("A genome-wide association study reveals susceptibility loci for myocardial infarction/coronary artery disease in Saudi Arabs" Wakil et al. (2015) [1] ). Several loci were described that conferred risk for CAD or MI, some of which were validated in an independent set of samples. Principal Component (PCA) analysis suggested that the Saudi Cohort was close to the CEU and TSI populations, thus pointing to similarity with European populations.
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ItemProtocol for a retrospective, controlled cohort study of the impact of a change in Nature journals' editorial policy for life sciences research on the completeness of reporting study design and execution(SPRINGER, 2016-07)In recent years there has been increasing concern about the rigor of laboratory research. Here we present the protocol for a study comparing the completeness of reporting of in vivo and in vitro research carried in Nature Publication Group journals before and after the introduction of a change in editorial policy (the introduction of a set of guidelines for reporting); and in similar research published in other journals in the same periods.
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ItemAntibody-Drug Conjugates for Cancer Therapy(MDPI, 2016-09)Antibody-drug conjugates (ADCs) take advantage of the specificity of a monoclonal antibody to deliver a linked cytotoxic agent directly into a tumour cell. The development of these compounds provides exciting opportunities for improvements in patient care. Here, we review the key issues impacting on the clinical success of ADCs in cancer therapy. Like many other developing therapeutic classes, there remain challenges in the design and optimisation of these compounds. As the clinical applications for ADCs continue to expand, key strategies to improve patient outcomes include better patient selection for treatment and the identification of mechanisms of therapy resistance.
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ItemYoung Children with ASD Use Lexical and Referential Information During On-line Sentence Processing(FRONTIERS MEDIA SA, 2016-02-19)Research with adults and older children indicates that verb biases are strong influences on listeners' interpretations when processing sentences, but they can be overruled. In this paper, we ask two questions: (i) are children with Autism Spectrum Disorder (ASD) who are high functioning sensitive to verb biases like their same age typically developing peers?, and (ii) do young children with ASD and young children with typical development (TD) override strong verb biases to consider alternative interpretations of ambiguous sentences? Participants were aged 5-9 years (mean age 6.65 years): children with ASD who were high functioning and children with TD. In task 1, biasing and neutral verbs were included (e.g., eat cake versus move cake). In task 2, the focus was on whether the prepositional phrase occurring with an instrument biasing verb (e.g., 'Chop the tree with the axe') was interpreted as an instrument even if the named item was an implausible instrument (e.g., candle in 'Cut the cake with the candle'). Overall, the results showed similarities between groups but the ASD group was generally slower. In task 1, both groups looked at the named object faster in the biasing than the non-biasing condition, and in the biasing condition the ASD group looked away from the target more quickly than the TD group. In task 2, both groups identified the target in the prepositional phrase. They were more likely to override the verb instrument bias and consider the alternative (modification) interpretation in the implausible condition (e.g., looking at the picture of a cake with a candle on it'). Our findings indicate that children of age 5 years and above can use context to override verb biases. Additionally, an important component of the sentence processing mechanism is largely intact for young children with ASD who are high functioning. Like children with TD, they draw on verb semantics and plausibility in integrating information. However, they are likely to be slower in processing the language they hear. Based on previous findings of associations between processing speed and cognitive functioning, the implication is that their understanding will be negatively affected, as will their academic outcomes.
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ItemOptimizing combination dabrafenib and trametinib therapy in BRAF mutation-positive advanced melanoma patients: Guidelines from Australian melanoma medical oncologists(WILEY-BLACKWELL, 2016-12)BRAF mutations occur commonly in metastatic melanomas and inhibition of mutant BRAF and the downstream kinase MEK results in rapid tumor regression and prolonged survival in patients. Combined therapy with BRAF and MEK inhibition improves response rate, progression free survival and overall survival compared with single agent BRAF inhibition, and reduces the skin toxicity that is seen with BRAF inhibitor monotherapy. However, this combination is associated with an increase in other toxicities, particularly drug-related pyrexia, which affects approximately 50% of patients treated with dabrafenib and trametinib (CombiDT). We provide guidance on managing adverse events likely to arise during treatment with combination BRAF and MEK inhibition with CombiDT: pyrexia, skin conditions, fatigue; and discuss management of CombiDT during surgery and radiotherapy. By improving tolerability and in particular preventing unnecessary treatment cessations or reduction in drug exposure, best outcomes can be achieved for patients undergoing CombiDT therapy.
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ItemFluorine-18 radiolabeling of a nitrophenyl sulfoxide and its evaluation in an SK-RC-52 model of tumor hypoxia(WILEY-BLACKWELL, 2016-08)The significance of imaging hypoxia with the positron emission tomography ligand [(18) F]FMISO has been demonstrated in a variety of cancers. However, the slow kinetics of [(18) F]FMISO require a 2-h delay between tracer administration and patient scanning. Labeled chloroethyl sulfoxides have shown faster kinetics and higher contrast than [(18) F]FMISO in a rat model of ischemic stroke. However, these nitrogen mustard analogues are unsuitable for routine production and use in humans. Here, we report on the synthesis and in vitro and in vivo evaluation of a novel sulfoxide, which contains an ester moiety for hydrolysis and subsequent trapping in hypoxic cells. Non-decay corrected yields of radioactivity were 1.18 ± 0.24% (n = 27, 2.5 ± 0.5% decay corrected radiochemical yield) based on K[(18) F]F. The radiotracer did not show any defluorination and did not undergo metabolism in an in vitro assay using S9 liver fractions. Imaging studies using an SK-RC-52 tumor model in BALB/c nude mice have revealed that [(18) F]1 is retained in hypoxic tumors and has similar hypoxia selectivity to [(18) F]FMISO. Because of a three times faster clearance rate than [(18) F]FMISO from normoxic tissue, [(18) F]1 has emerged as a promising new radiotracer for hypoxia imaging.
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ItemTemporal lobe epilepsy following maintenance electroconvulsive therapyElectrical kindling in the human brain?(WILEY-BLACKWELL, 2016-11)Maintenance electroconvulsive therapy (ECT) is sometimes prescribed for refractory psychiatric conditions. We describe five patients who received maintenance ECT and developed florid temporal epileptiform abnormalities on electroencephalography (EEG) despite no history of epilepsy and normal neuroimaging. All patients had received regular ECT for at least 8 months. Three patients had clinical events consistent with epileptic seizures, and video-EEG monitoring captured electrographic seizures in two patients. After cessation of ECT the EEGs normalized in all patients, and no further clinical seizures occurred. Maintenance ECT may predispose to epilepsy with a seizure focus in the temporal lobe.
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ItemSystematic review with meta-analysis: fundic gland polyps and proton pump inhibitors(WILEY, 2016-11)BACKGROUND: A causal association between proton pump inhibitor (PPI) use and fundic gland polyps has been suggested, but the data are conflicting. AIM: To clarify the relationship through a meta-analysis of the existing data. METHODS: A systematic retrieval and selection of records was performed. The main inclusion criteria were original studies reporting the prevalence of fundic gland polyps in PPI users or the reverse, compared to controls. Key outcomes were the odds ratios (OR) for fundic gland polyp prevalence in association with PPI use, prevalence of PPI use amongst subjects with fundic gland polyps and fundic gland polyp prevalence among PPI users. Statistical analysis was performed using Mix 2.0 Pro. RESULTS: The initial search using electronic databases and manual searching retrieved 339 peer-reviewed articles and abstracts. Twenty articles met all inclusion and exclusion criteria, with a total of 40 218 subjects included. The meta-analysis of 12 studies revealed an increase in fundic gland polyps amongst PPI users compared to controls (OR 2.46, 95% CI 1.42-4.27, P = 0.001), particularly among individuals taking PPIs for at least 6 months (OR: 4.71, 95% CI 2.22-9.99, P < 0.001) or 12 months (OR: 5.32, 95% CI 2.58-10.99, P < 0.001). CONCLUSIONS: Proton pump inhibitor usage is associated with a significantly increased prevalence of fundic gland polyps, and there is a trend for this to increase with longer length of PPI exposure. However, the meta-analysis is limited mainly to cohort studies.