Medicine and Health Sciences Commons^™

Astrocytic Modulation Of Cortical Oscillations, Alba Bellot-Saez, Greg Cohen, Andre Van Schaik, Lezanne Ooi, John W. Morley, Yossi Buskila

Illawarra Health and Medical Research Institute

Brain waves are rhythmic voltage oscillations emerging from the synchronization of individual neurons into a neuronal network. These oscillations range from slow to fast fluctuations, and are classified by power and frequency band, with different frequency bands being associated with specific behaviours. It has been postulated that at least ten distinct mechanisms are required to cover the frequency range of neural oscillations, however the mechanisms that gear the transition between distinct oscillatory frequencies are unknown. In this study, we have used electrophysiological recordings to explore the involvement of astrocytic K⁺ clearance processes in modulating neural oscillations at both network …

Stoichiometry Dependent Inhibition Of Rat Α3Β4 Nicotinic Acetylcholine Receptor By The Ribbon Isomer Of Α-Conotoxin Auib, Xiaosa Wu, Han Shen Tae, Yen-Hua Huang, David J. Adams, David J. Craik, Quentin Kaas

Illawarra Health and Medical Research Institute

The ribbon isomer of α-conotoxin AuIB has 10-fold greater potency than the wild-type globular isomer at inhibiting nicotinic acetylcholine receptors (nAChRs) in rat parasympathetic neurons, and unlike its globular isoform, ribbon AuIB only targets a specific stoichiometry of the α3β4 nAChR subtype. Previous electrophysiological recordings of AuIB indicated that ribbon AuIB binds to the α3(+)α3(−) interface within the nAChR extracellular domain, which is displayed by the (α3)₃(β4)₂ stoichiometry but not by (α3)₂(β4)₃. This specificity for a particular stoichiometry is remarkable and suggests that ribbon isoforms of α-conotoxins might have great potential in drug …

Transcription Factor Tbx18 Induces The Differentiation Of C-Kit+Canine Mesenchymal Stem Cells (Cmscs) Into San-Like Pacemaker Cells In A Co-Culture Model In Vitro, Hua Xiao, Yong-Jun Yang, Yi-Zhang Lin, Song Peng, Shu Lin, Zhi-Yuan Song

Illawarra Health and Medical Research Institute

Bone mesenchymal stem cells (MSCs), as well as cardiomyocytes, are derived from early mesoderm, becoming committed to their fate under the influence of different differentiation factors. We examined whether the overexpression of Tbx18 can induce the differentiation of c-kit⁺ cMSCs into a phenotype similar to that of native pacemaker cells and whether these transfected cells can couple to adjacent atrial cells with functional consequences. The c-kit⁺ cMSCs were first sorted, then transfected with different lentiviral vectors. Tbx18-c-kit⁺ cMSCs represented the experimental group, while EYFP-c-kit⁺ cMSCs and canine sinoatrial node (SAN) cells were used as controls. Within …

Novel Analgesic Ω-Conotoxins From The Vermivorous Cone Snail Conus Moncuri Provide New Insights Into The Evolution Of Conopeptides, Silmara Sousa, Jeffrey R. Mcarthur, Andreas Brust, Rebecca Bhola, K. . Johan Rosengren, L Ragnarsson, Sebastien Dutertre, Paul F. Alewood, Macdonald J. Christie, David J. Adams, Irina Vetter, Richard J. Lewis

Illawarra Health and Medical Research Institute

Cone snails are a diverse group of predatory marine invertebrates that deploy remarkably complex venoms to rapidly paralyse worm, mollusc or fish prey. ω-Conotoxins are neurotoxic peptides from cone snail venoms that inhibit Ca_v2.2 voltage-gated calcium channel, demonstrating potential for pain management via intrathecal (IT) administration. Here, we isolated and characterized two novel ω-conotoxins, MoVIA and MoVIB from Conus moncuri, the first to be identified in vermivorous (worm-hunting) cone snails. MoVIA and MoVIB potently inhibited human Ca_v2.2 in fluorimetric assays and rat Ca_v2.2 in patch clamp studies, and both potently displaced radiolabeled ω-conotoxin …

A Systematic Benchmarking Of Computational Vibrational Spectroscopy With Dftb3: Normal Mode Analysis And Fast Fourier Transform Dipole Autocorrelation Function, Venkatasaisandeep Inakollu, Haibo Yu

Illawarra Health and Medical Research Institute

Computational vibrational spectroscopy serves as an important tool in the interpretation of experimental infrared (IR) spectra. In this article, we present a systematic benchmarking study of DFTB3 with two different computational vibrational spectroscopic methods, based on either normal mode analysis (NMA) or fast Fourier transform dipole autocorrelation function (FT‐DAC). The results were compared with experimental data and theoretical calculations with B3LYP/cc‐pVTZ. The empirical scaling factors for DFTB3/NMA, DFTB3‐freq/NMA, and DFTB3/FT‐DAC methods are 0.9993, 1.0059, and 0.9982, respectively. We also demonstrate the significance of anharmonicity and conformational sampling in vibrational spectroscopic calculations on flexible molecules. As expected, DFTB3/FT‐DAC predicted the anharmonic …

Modelling The Dorsal Root Ganglia Using Human Pluripotent Stem Cells: A Platform To Study Peripheral Neuropathies, Serena Viventi, Mirella Dottori

Illawarra Health and Medical Research Institute

Sensory neurons of the dorsal root ganglia (DRG) are the primary responders to stimuli inducing feelings of touch, pain, temperature, vibration, pressure and muscle tension. They consist of multiple subpopulations based on their morphology, molecular and functional properties. Our understanding of DRG sensory neurons has been predominantly driven by rodent studies and using transformed cell lines, whereas less is known about human sensory DRG neurons simply because of limited availability of human tissue. Although these previous studies have been fundamental for our understanding of the sensory system, it is imperative to profile human DRG subpopulations as it is becoming evident …

6-Substituted Hexamethylene Amiloride (Hma) Derivatives As Potent And Selective Inhibitors Of The Human Urokinase Plasminogen Activator For Use In Cancer, Benjamin J. Buckley, Ashraf Abdel A. Aboelela, Elahe Minaei, Longguang Jiang, Zhihong Xu, Umar Ali, Karen J. Fildes, Chen Cheung, Simon M. Cook, Darren Johnson, Daniel Bachovchin, Gregory Cook, Minoti Apte, Mingdong Huang, Marie Ranson, Michael J. Kelso

Illawarra Health and Medical Research Institute

Metastasis is the cause of death in the majority (∼90%) of malignant cancers. The oral potassium-sparing diuretic amiloride and its 5-substituted derivative 5-N,N-(hexamethylene)amiloride (HMA) reportedly show robust antitumor/metastasis effects in multiple in vitro and animal models. These effects are likely due, at least in part, to inhibition of the urokinase plasminogen activator (uPA), a key protease determinant of cell invasiveness and metastasis. This study reports the discovery of 6-substituted HMA analogs that show nanomolar potency against uPA, high selectivity over related trypsin-like serine proteases, and minimal inhibitory effects against epithelial sodium channels (ENaC), the diuretic and antikaliuretic target of amiloride. …

Dosimetric Effects Of Brass Mesh Bolus On Skin Dose And Dose At Depth For Postmastectomy Chest Wall Irradiation, Zakiya Al-Rahbi, Dean L. Cutajar, Peter E. Metcalfe, Anatoly B. Rosenfeld

Illawarra Health and Medical Research Institute

Purpose: To investigate the feasibility of using the brass mesh bolus as an alternative to tissue- equivalent bolus for post mastectomy chest wall cancer by characterizing the dosimetric effects of the 2-mm fine brass bolus on both the skin dose, the dose at depth and spatial distribution.

Materials and methods: Surface dose and percent depth dose data were acquired for a 6 MV photon beam in a solid water phantom using MOSkin™ Gafchromic EBT3 film and an Advanced Markus ionization chamber. Data were acquired for the case of: no bolus, Face-up bass bolus, Face-down brass bolus, …

Bacterial Replisomes, Zhi-Qiang Xu, Nicholas E. Dixon

Illawarra Health and Medical Research Institute

Bacterial replisomes are dynamic multiprotein DNA replication machines that are inherently difficult for structural studies. However, breakthroughs continue to come. The structures of Escherichia coli DNA polymerase III (core)-clamp-DNA subcomplexes solved by single-particle cryo-electron microscopy in both polymerization and proofreading modes and the discovery of the stochastic nature of the bacterial replisomes represent notable progress. The structures reveal an intricate interaction network in the polymerase-clamp subassembly, providing insights on how replisomes may work. Meantime, ensemble and single-molecule functional assays and fluorescence microscopy show that the bacterial replisomes can work in a decoupled and uncoordinated way, with polymerases quickly exchanging and …

Nmr Structure Of Μ-Conotoxin Giiic: Leucine 18 Induces Local Repacking Of The N-Terminus Resulting In Reduced Nav Channel Potency, Peta J. Harvey, Nyoman D. Kurniawan, Rocio K. Finol Urdaneta, Jeffrey R. Mcarthur, Dorien Van Lysebetten, Thomas S. Dash, Justine M. Hill, David J. Adams, Thomas Durek, David J. Craik

Illawarra Health and Medical Research Institute

µ-Conotoxins are potent and highly specific peptide blockers of voltage-gated sodium channels. In this study, the solution structure of µ-conotoxin GIIIC was determined using 2D NMR spectroscopy and simulated annealing calculations. Despite high sequence similarity, GIIIC adopts a three-dimensional structure that differs from the previously observed conformation of µ-conotoxins GIIIA and GIIIB due to the presence of a bulky, non-polar leucine residue at position 18. The side chain of L18 is oriented towards the core of the molecule and consequently the N-terminus is re-modeled and located closer to L18. The functional characterization of GIIIC defines it as a canonical µ-conotoxin …

A Whole Of School Intervention For Personality Disorder And Self-Harm In Youth: A Pilot Study Of Changes In Teachers' Attitudes, Knowledge And Skills, Michelle L. Townsend, Annaleise Gray, Tanya M. Lancaster, Brin F. S Grenyer

Illawarra Health and Medical Research Institute

Background The school environment offers an ideal opportunity for early identification and intervention for youth with self-harm and complex mental health issues, such as borderline personality disorder (BPD). Yet, class teachers often report minimal knowledge, feeling ill-equipped to respond, and experience high levels of stress when exposed to such challenges. Research is required to understand how training and development activities led by school counsellors may enhance teacher attitudes, confidence and knowledge of self-harm and complex mental health issues, such as BPD. We aimed to explore the extent that a whole of school initiative might enhance capacity for early identification and …

Treatment Of Personality Disorder Using A Whole Of Service Stepped Care Approach: A Cluster Randomized Controlled Trial, Brin F. S Grenyer, Kate L. Lewis, Mahnaz Fanaian, Beth Kotze

Illawarra Health and Medical Research Institute

Background and objectives People with personality disorders are prevalent in emergency and inpatient mental health services. We examined whether implementing a stepped care model of psychological therapy reduces demand on hospital units by people with personality disorder, in a cluster randomized controlled trial.

Method A total of 642 inpatients (average age 36.8, 50.5% female) with a primary ICD-10 personality disorder were recruited during 18 months baseline, then monitored during an 18 month active trial phase. In the active trial phase two equivalent sites were randomised to either treatment as usual (TAU), or a whole of service intervention that diverted people …

Bdnf As A Pharmacogenetic Target For Antipsychotic Treatment Of Schizophrenia, Mei Han, Chao Deng

Illawarra Health and Medical Research Institute

Antipsychotic drugs remain the mainstay of pharmacotherapy for schizophrenia. As there are large individual variations in efficacy and side-effects of antipsychotic drugs, there is a strong demand for personalized medication to treat schizophrenia. Pharmacogenetic research into antipsychotic drugs has examined a number of genetic variants and only a few polymorphisms have been found which promise to be associated with the therapeutic efficacy and side-effects of antipsychotic drugs. Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a major role in neurogenesis and neuroplasticity, and in the modulation of several neurotransmitter systems including the dopaminergic system involved in the pathophysiology of …

Clusterin From Human Clinical Tear Samples: Positive Correlation Between Tear Concentration And Schirmer Strip Test Results, Valerie Yu, Dhruva Bhattacharya, Andrew Webster, Aditi Bauskar, Charles Flowers, Martin Heur, Shravan Chintala, Tatsuo Itakura, Mark R. Wilson, Joseph T. Barr, Shinwu Jeong, Mingwu Wang, M Elizabeth Fini

Illawarra Health and Medical Research Institute

Purpose: To investigate the relationship between tear concentration of the homeostatic protein clusterin (CLU) and dry eye signs and symptoms, and to characterize tear CLU protein.

Methods: Two independent studies were conducted, one in Tucson (44 subjects), the other in Los Angeles (52 subjects). A cohort study design was employed to enroll patients without regard to dry eye diagnosis. Dry eye signs and symptoms were assessed using clinical tests. Tear samples were collected by Schirmer strip, and also by micropipette at slit lamp when possible. CLU from both sample types was quantified by immunoassay. The relationship between CLU …

The Effect Of Dna Backbone On The Triplet Mechanism Of Uv-Induced Thymine-Thymine (6-4) Dimer Formation, Xingyong Wang, Haibo Yu

Illawarra Health and Medical Research Institute

Density functional theory calculations have been carried out to investigate the formation mechanism of the thymine-thymine (6-4) dimer ((6-4)TT), which is one of the main DNA lesions induced by ultraviolet radiation and is closely related to skin cancers. The DNA backbone was found to have nonnegligible effects on the triplet reaction pathway, particularly the reaction steps involving substantial base rotations. The mechanism for the isomerisation from (6-4)TT to its Dewar valence isomer (DewarTT) was also explored, confirming the necessity of absorbing a second photon. In addition, the solvation effects were examined and showed considerable influence on the potential energy surface.

Personal Exposure To Radio Frequency Electromagnetic Fields Among Australian Adults, Berihun Zeleke, Christopher Brzozek, Chhavi Bhatt, Michael J. Abramson, Rodney J. Croft, Frederik Freudenstein, Peter M. Wiedemann, Geza P. Benke

Illawarra Health and Medical Research Institute

The measurement of personal exposure to radiofrequency electromagnetic fields (RF-EMFs) is important for epidemiological studies. RF-EMF exposure can be measured using personal exposimeters that register RF-EMFs over a wide range of frequency bands. This study aimed to measure and describe personal RF-EMF exposure levels from a wide range of frequency bands. Measurements were recorded from 63 participants over an average of 27.4 (±4.5) hours. RF-EMF exposure levels were computed for each frequency band, as well as from downlink (RF from mobile phone base station), uplink (RF from mobile phone handsets), broadcast, and Wi-Fi. Participants had a mean (±SD) age of …

Social Media In Dietetics: Insights Into Use And User Networks, Yasmine Probst, Qingcai Peng

Illawarra Health and Medical Research Institute

Aim: Social media has transformed the interaction between healthcare professionals and consumers, yet research of its use in dietetics is limited. The aim of this study was to investigate the influence of dietetic user networks on use of social media and test the applicability of a social media metrics tool to determine influential users.

Methods: An online survey about social media use and practices based on the scientific literature was developed and implemented online with dietitians. Feasibility of a social media metrics analysis was conducted via Twitter using the NodeXL metrics tool to determine influential dietetic networks based …

Dual Transcriptomics Of Host-Pathogen Interaction Of Cystic Fibrosis Isolate Pseudomonas Aeruginosa Pass1 With Zebrafish, Sheemal S. Kumar, Julia I. Tandberg, Anahit Penesyan, Liam Elbourne, Nadia E. Suarez-Bosche, Emily Don, Eline Skadberg, Federico Fenaroli, Nicholas Cole, Hanne Cecilie Winther-Larsen, Ian T. Paulsen

Illawarra Health and Medical Research Institute

Pseudomonas aeruginosa is a significant cause of mortality in patients with cystic fibrosis (CF). To explore the interaction of the CF isolate P. aeruginosa PASS1 with the innate immune response, we have used Danio rerio (zebrafish) as an infection model. Confocal laser scanning microscopy (CLSM) enabled visualization of direct interactions between zebrafish macrophages and P. aeruginosa PASS1. Dual RNA-sequencing of host-pathogen was undertaken to profile RNA expression simultaneously in the pathogen and the host during P. aeruginosa infection. Following establishment of infection in zebrafish embryos with PASS1, 3 days post infection (dpi), there were 6739 genes found to be significantly …

Targeting Of N-Type Calcium Channels Via Gabab-Receptor Activation By Α-Conotoxin Vc1.1 Variants Displaying Improved Analgesic Activity, Fengtao Cai, Ning Xu, Zhuguo Liu, Rong Ding, Shuo Yu, Mingxin Dong, Shuo Wang, Jintao Shen, Han Shen Tae, David J. Adams, Xuerong Zhang, Qiuyun Dai

Illawarra Health and Medical Research Institute

α-Conotoxins exhibiting analgesic activity, such as Vc1.1, have been shown to inhibit α9α10 nicotinic acetylcholine receptors (nAChRs) and GABA_B-receptor (GABA_BR) coupled N-type (Ca_V2.2) calcium channels. Here, we report two Vc1.1 variants, Vc1.1[N9R] and benzoyl-Vc1.1[N9R], that selectively inhibit Ca_V2.2 channels via GABA_BR activation but exhibit reduced inhibitory activity at α9α10 and other neuronal nAChR subtypes compared with Vc1.1. Surprisingly, the analgesic activity of Vc1.1[N9R] and benzoyl-Vc1.1[N9R] was more potent than that of Vc1.1 when tested in partial sciatic nerve ligation injury and chronic constriction injury models. Vc1.1[N9R] and benzoyl-Vc1.1[N9R] exhibited either …

Obesity, Altered Oxidative Stress, And Clinical Correlates In Chronic Schizophrenia Patients, Hui-Mei An, Xiangdong Du, Xingbing Huang, Lingyan Qi, Qiufang Jia, Guangzhong Yin, Chunling Xiao, Xu-Feng Huang, Yuping Ning, Ryan Cassidy, Li Wang, Jair C. Soares, Xiang Yang Zhang

Illawarra Health and Medical Research Institute

Antipsychotic pharmacotherapy is strongly obesogenic and is associated with increased oxidative stress in patients with schizophrenia. However, whether these changes reflect psychopathology, antipsychotic efficacy, or some other factor is not known. Our study aims to investigate the degree of oxidative stress in different BMI categories and to identify clinical symptomatology that may be paired with increased oxidative stress in a schizophrenia population. To this end, we performed a cross-sectional study and recruited 89 long-term inpatients with schizophrenia and collected the following variables: plasma malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), routine biochemical analysis, and psychopathology through …

Sod1a4v Aggregation Alters Ubiquitin Homeostasis In A Cell Model Of Als, Natalie E. Farrawell, Isabella Lambert-Smith, Kristen Mitchell, Jessie Mckenna, Luke Mcalary, Prajwal Ciryam, Kara L. Vine, Darren N. Saunders, Justin J. Yerbury

Illawarra Health and Medical Research Institute

A hallmark of amyotrophic lateral sclerosis (ALS) pathology is the accumulation of ubiquitylated protein inclusions within motor neurons. Recent studies suggest the sequestration of ubiquitin (Ub) into inclusions reduces the availability of free Ub, which is essential for cellular function and survival. However, the dynamics of the Ub landscape in ALS have not yet been described. Here, we show that Ub homeostasis is altered in a cell model of ALS induced by expressing mutant SOD1 (SOD1^A4V). By monitoring the distribution of Ub in cells expressing SOD1^A4V, we show that Ub is present at the earliest stages …

Exposure To High-Frequency Electromagnetic Field Triggers Rapid Uptake Of Large Nanosphere Clusters By Pheochromocytoma Cells, Palalle G. Tharushi Perera, The Hong Phong Nguyen, Chaitali Dekiwadia, Jason V. Wandiyanto, I Sbarski, Olga Bazaka, Kateryna Bazaka, Russell Crawford, Rodney J. Croft, Elena Ivanova

Illawarra Health and Medical Research Institute

Background: Effects of man-made electromagnetic fields (EMF) on living organisms potentially include transient and permanent changes in cell behaviour, physiology and morphology. At present, these EMF-induced effects are poorly defined, yet their understanding may provide important insights into consequences of uncontrolled (e.g., environmental) as well as intentional (e.g., therapeutic or diagnostic) exposure of biota to EMFs. In this work, for the first time, we study mechanisms by which a high frequency (18 GHz) EMF radiation affects the physiology of membrane transport in pheochromocytoma PC 12, a convenient model system for neuro-toxicological and membrane transport studies.

Methods and results: …

Mobile Phone Use And Incidence Of Brain Tumour Histological Types, Grading Or Anatomical Location: A Populationbased Ecological Study, Ken Karipidis, Mark Elwood, Geza P. Benke, Masoumeh Sanagou, Lydiawati Tjong, Rodney J. Croft

Illawarra Health and Medical Research Institute

Objective Some studies have reported increasing trends in certain brain tumours and a possible link with mobile phone use has been suggested. We examined the incidence time trends of brain tumour in Australia for three distinct time periods to ascertain the influence of improved diagnostic technologies and increase in mobile phone use on the incidence of brain tumours.

Design In a population-based ecological study, we examined trends of brain tumour over the periods 1982- 1992, 1993-2002 and 2003-2013. We further compared the observed incidence during the period of substantial mobile phone use (2003-2013) with predicted (modelled) incidence for the same …

Microglia Activation In The Offspring Of Prenatal Poly I: C Exposed Rats: A Pet Imaging And Immunohistochemistry Study, Xue Li, Xin Tian, Luxian Lv, Gangrui Hei, Xu-Feng Huang, Xiaoduo Fan, Jinming Zhang, Jianjiang Zhang, Lijuan Pang, Xueqin Song

Illawarra Health and Medical Research Institute

Background The well-known ‘pyrotherapy’ of Julius Wagner-Jauregg might be the beginning of the study on the immunological concepts of schizophrenia. As the primary immune effector cells in the brain, microglia play a pivotal role in neuroinflammatory processes. Maternal viral infection during pregnancy is associated with an increased risk for psychiatric disorders with presumed neurodevelopmental origin, including autism spectrum disorders and schizophrenia. The present study was to quantify microglia activation in vivo in the mature offspring of rats exposed to polyriboinosinic–polyribocytidilicacid (Poly I:C) during pregnancy using ¹¹C-PK11195 positron emission tomography (PET) and immunohistochemistry.

Objective The study aimed to quantify microglia …

A High-Throughput Method For The Analysis Of Erythrocyte Fatty Acids And The Omega-3 Index, Ayedh Alqarni, Kiara Mcintyre, Simon H. J Brown, Barbara J. Meyer, Todd W. Mitchell

Illawarra Health and Medical Research Institute

Omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) have several health benefits. In particular, low n-3 LCPUFA status is associated with cardiovascular disease (CVD) and led to the development of the omega-3 index that is the proportion of eicosapentaenoic acid and docosahexaenoic acid in the erythrocyte membranes, as a marker of CVD risk. Most methods used to measure the omega-3 index are laborious and time consuming. Therefore, the aim of this study was to develop a high-throughput method for the extraction and measurement of erythrocyte fatty acids and the omega-3 index. For sample extraction and quantification, two methods were used; a …

Could An Allied Health Care Approach Reduce The Unacceptable Incidence Of Suicide After Psychiatric Hospital Discharge?, Katrina Weston-Green, Ashleigh L. Osborne, Kelly A. Newell

Illawarra Health and Medical Research Institute

We propose that an allied care model could assist to reduce the unacceptably high incidence of suicide after psychiatric hospital discharge. A designated care coordinator is needed to provide holistic discharge planning that incorporates medical, functional and social support for the patient. At a minimum, this approach must include assessment of suicide means access and modifications to the home environment to reduce risk of injury as a standard management procedure.

Defining And Developing A Generic Framework For Monitoring Data Quality In Clinical Research, Lauren Houston, Ping Yu, Allison Martin, Yasmine Probst

Illawarra Health and Medical Research Institute

Evidence for the need for high data quality in clinical research is well established. The rigor of clinical research conclusions rely heavily on good quality data, which relies on good documentation practices. Little attention has been given to clear guidelines and definitions to monitor data quality. To address this, a "fit-for-use" data quality monitoring framework (DQMF) for clinical research was developed based on a holistic design-oriented approach. An integrated literature review and feasibility study underpinned the framework development. Ontology of key terms, concepts, methods, and standards were recorded using a consensus approach and mind mapping technique. The DQMF is presented …

Assessing Data Quality And The Variability Of Source Data Verification Auditing Methods In Clinical Research Settings, Lauren Houston, Yasmine Probst, Allison Martin

Illawarra Health and Medical Research Institute

Introduction: Data audits within clinical settings are extensively used as a major strategy to identify errors, monitor study operations and ensure high-quality data. However, clinical trial guidelines are non-specific in regards to recommended frequency, timing and nature of data audits. The absence of a well-defined data quality definition and method to measure error undermines the reliability of data quality assessment. This review aimed to assess the variability of source data verification (SDV) auditing methods to monitor data quality in a clinical research setting.

Material and methods: The scientific databases MEDLINE, Scopus and Science Direct were searched for English …

Characterisation And Evaluation Of A Pnp Strip Detector For Synchrotron Microbeam Radiation Therapy, Jeremy A. Davis, Jason Paino, Andrew Dipuglia, Matthew Cameron, Rainer Siegele, Zeljko Pastuovic, Marco Petasecca, Vladimir Perevertaylo, Anatoly B. Rosenfeld, Michael L. F Lerch

Illawarra Health and Medical Research Institute

The Quality Assurance requirements of detectors for Synchrotron Micro-beam Radiation Therapy are such that there are limited commercial systems available. The high intensity and spatial fractionation of synchrotron microbeams requires detectors be radiation hard and capable of measuring high dose gradients with high spatial resolution sensitivity. Silicon single strip detectors are a promising candidate for such applications. The PNP strip detector is an alternative design of an already proven technology and is assessed on its contextual viability. In this study, the electrical and charge collection efficiency properties of the device are characterised. In addition, a dedicated TCAD model is used …

Antibacterial Properties Of Four Novel Hit Compounds From A Methicillin-Resistant Staphylococcus Aureus-Caenorhabditis Elegans High-Throughput Screen, Nagendran Tharmalingam, Rajmohan Rajmuthiah, Wooseong Kim, Beth Fuchs, Elamparithi Jeyamani, Michael J. Kelso, Eleftherios Mylonakis

Illawarra Health and Medical Research Institute

There is an urgent need for the discovery of effective new antimicrobial agents to combat the rise of bacterial drug resistance. High-throughput screening (HTS) in whole-animal infection models is a powerful tool for identifying compounds that show antibacterial activity and low host toxicity. In this report, we characterize the activities of four novel antistaphylococcal compounds identified from an HTS campaign conducted using Caenorhabditis elegans nematodes infected with methicillin-resistant Staphylococcus aureus (MRSA). The hit compounds included an Nhydroxy indole-1, a substituted melamine derivative-2, N-substituted indolic alkyl isothiocyanate-3, and pdifluoromethylsulfide analog-4 of the well-known protonophore carbonyl cyanide m-chlorophenyl hydrazone. Minimal inhibitory concentrations …