Medicine and Health Sciences Commons^™

Understanding The Role Of Apoe Fragments In Alzheimer's Disease, Sonia Sanz Munoz, Brett Garner, Lezanne Ooi

Illawarra Health and Medical Research Institute

Alzheimer's disease (AD) is one of the most devastating neurodegenerative diseases. It has been known for decades that the APOE ɛ4 allele is the most significant genetic risk factor for late-onset AD and yet its precise role in the disease remains unclear. The APOE gene encodes apolipoprotein E (apoE), a 35 kDa glycoprotein highly expressed in the brain. There are three different isoforms: apoE3 is the most common allele in the population, whilst apoE2 decreases, and apoE4 increases AD risk. ApoE has numerous functions that affect neuronal and non-neuronal cells, thus how it contributes to disease onset and progression is …

Synthesis Of Methotrexate-Loaded Tantalum Pentoxide-Poly(Acrylic Acid) Nanoparticles For Controlled Drug Release Applications, Kathrin Bogusz, Malgorzata Zuchora, Vitor Sencadas, Moeava Tehei, Michael L. F Lerch, Nathan Thorpe, Anatoly B. Rosenfeld, Shi Xue Dou, Hua-Kun Liu, Konstantin K. Konstantinov

Illawarra Health and Medical Research Institute

Over the past decade, there has been increasing interest in the use of multifunctional nanoparticles (NPs) for cancer treatment. Of importance are systems that can deliver drugs at a sustained rate to target cancer cells, which can result in higher efficiency and reduced systemic toxicity. In this study, we present the route for the synthesis of tantalum pentoxide (Ta₂O₅) NPs with a particle size of 27 nm that were individually coated with poly(acrylic acid) (PAA) with a different layer thickness of 2-8 nm by in-situ polymerization of the acrylic acid monomer. The capability of Ta_{2 …}

Early Antipsychotic Exposure Affects Nmda And Gabaa Receptor Binding In The Brains Of Juvenile Rats, Jiamei Lian, Chao Deng

Illawarra Health and Medical Research Institute

Antipsychotics were developed to treat schizophrenia in adults; however they have been increasingly prescribed in children and adolescents. The NMDA and GABAA receptors are involved in neurodevelopment and the pathophysiology of various mental disorders in children and adolescents. Male and female juvenile rats were treated orally with risperidone (0.3 mg/kg, 3 times/day), aripiprazole (1 mg/kg), olanzapine (1 mg/kg) or vehicle (control), starting from postnatal day (PD) 23 (±1 day) for 3 weeks (corresponding to the childhood-adolescent period in humans). Quantitative autoradiography was used to detect the binding density of [³H]MK-801 (an NMDA receptor antagonist) and [³H]muscimol …

Illawarra Born Cross-Generational Health Study: Feasibility Of A Multi-Generational Birth Cohort Study, Michelle L. Townsend, Megan A. Kelly, Judith A. Pickard, Theresa A. Larkin, Victoria M. Flood, Peter Caputi, Ian M. R Wright, Alison L. Jones, Brin F. S Grenyer

Illawarra Health and Medical Research Institute

Background: There is a strong interest in the concept of developmental origins of health and disease and their influence on various factors "from cradle to grave". Despite the increasing appreciation of this lifelong legacy across the human life course, many gaps remain in the scientific understanding of mechanisms influencing these formative phases. Cross-generational susceptibility to health problems is emerging as a focus of research in the context of birth cohort studies. The primary aim of the Illawarra Born study is to make scientific discoveries associated with improving health and wellbeing across the lifespan, with a particular focus on preventable …

A Stepped Wedge Cluster Randomised Trial Of A Cognitive Remediation Intervention In Alcohol And Other Drug (Aod) Residential Treatment Services, Jamie Berry, Isabella Jacomb, Jo Lunn, Antoinette Sedwell, Anthony Shakeshaft, Peter James Kelly, Pooria Sarrami, Megan James, Skye Russell, Talia Nardo, Daniel Barker, Jennifer Holmes

Illawarra Health and Medical Research Institute

Background: Executive functioning impairment is common in substance use disorder and is a major risk factor for poor treatment outcomes, including treatment drop-out and relapse. Cognitive remediation interventions seek to improve executive functioning and offer a promising approach to increase the efficacy of alcohol and other drug (AOD) treatments and improve long-term therapeutic outcomes. This protocol describes a study funded by the NSW Agency for Clinical Innovation that assesses the effectiveness of delivering a six-week group-based intervention of cognitive remediation in an ecologically valid sample of people attending residential AOD treatment services. We primarily aim to investigate whether cognitive …

Novel Dual-Action Prodrug Triggers Apoptosis In Glioblastoma Cells By Releasing A Glutathione Quencher And Lysine-Specific Histone Demethylase 1a Inhibitor, Martin Engel, Yi Sing Gee, Dale Cross, Alan T. Maccarone, Benjamin Heng, Amy Hulme, Grady Smith, Gilles Guillemin, Brett Stringer, Christopher J. T Hyland, Lezanne Ooi

Illawarra Health and Medical Research Institute

Targeting epigenetic mechanisms has shown promise against several cancers but has so far been unsuccessful against glioblastoma (GBM). Altered histone 3 lysine 4 methylation and increased lysine‐specific histone demethylase 1A (LSD1) expression in GBM tumours nonetheless suggest that epigenetic mechanisms are involved in GBM. We engineered a dual‐action prodrug, which is activated by the high hydrogen peroxide levels associated with GBM cells. This quinone methide phenylaminecyclopropane prodrug releases the LSD1 inhibitor 2‐phenylcyclopropylamine with the glutathione scavenger para‐quinone methide to trigger apoptosis in GBM cells. Quinone methide phenylaminocyclopropane impaired GBM cell behaviours in two‐dimensional and three‐dimensional assays, and triggered cell apoptosis …

What Do Individuals With Borderline Personality Disorder Want From Treatment? A Study Of Self-Generated Treatment And Recovery Goals, Fiona Y. Ng, Phoebe Carter, Marianne E. Bourke, Brin F. S Grenyer

Illawarra Health and Medical Research Institute

Outcome measurement has progressed in the field of personality disorders. While the majority of trials have evaluated outcomes on the basis of symptom and diagnostic indices, what is considered a meaningful and valued outcome to individuals has seldom been investigated. Self-generated treatment goals were collected from 102 individuals seeking treatment for borderline personality disorder and independently coded by 2 raters. Responses were content-analyzed to determine the categories of goals people want for treatment. A total of 464 individual goal units across 4 main goal types emerged in the content analysis: reducing symptoms, improved well-being, better interpersonal relationships, and having a …

The Endocannabinoid System And Cannabidiol's Promise For The Treatment Of Substance Use Disorder, Yann Chye, Erynn Christensen, Nadia Solowij, Murat Yucel

Illawarra Health and Medical Research Institute

Substance use disorder is characterized by repeated use of a substance, leading to clinically significant distress, making it a serious public health concern. The endocannabinoid system plays an important role in common neurobiological processes underlying substance use disorder, in particular by mediating the rewarding and motivational effects of substances and substance-related cues. In turn, a number of cannabinoid drugs (e.g., rimonabant, nabiximols) have been suggested for potential pharmacological treatment for substance dependence. Recently, cannabidiol (CBD), a non-psychoactive phytocannabinoid found in the cannabis plant, has also been proposed as a potentially effective treatment for the management of substance use disorder. Animal …

The United Chemicals Of Cannabis: Beneficial Effects Of Cannabis Phytochemicals On The Brain And Cognition, Katrina Weston-Green

Illawarra Health and Medical Research Institute

‘Medicinal cannabis’ can be defined as pharmaceutical grade cannabis-based products used for the treatment of illness. Beneficial treatment effects of cannabidiol (CBD), a major non-intoxicating compound isolated from the cannabis plant, have been shown in multiple states of cognitive impairment, including neurodegenerative (Alzheimer’s, Huntington’s and Parkinson’s disease), neuroinflammatory (sepsis-induced encephalopathy) and neurological disorders (ischemic brain injury). CBD can also treat some of the symptoms of schizophrenia, including cognitive deficits (impairments in learning and memory), which is a major symptom domain of the illness that is largely resistant to existing antipsychotic medications. However, empirical evidence suggests the presence of an ‘entourage …

2d Monolithic Silicon-Diode Array Detectors In Megavoltage Photon Beams: Does The Fabrication Technology Matter? A Medical Physicist's Perspective, Nauljun Stansook, Giordano Biasi, Kananan Utitsarn, Marco Petasecca, Peter E. Metcalfe, Martin G. Carolan, Michael L. F Lerch, Vladimir Perevertaylo, Tomas Kron, Anatoly B. Rosenfeld

Illawarra Health and Medical Research Institute

A family of prototype 2D monolithic silicon-diode array detectors (MP512, Duo, Octa) has been proposed by the Centre for Medical Radiation Physics, University of Wollongong (Australia) for relative dosimetry in small megavoltage photon beams. These detectors, which differ in the topology of their 512 sensitive volumes, were originally fabricated on bulk p-type substrates. More recently, they have also been fabricated on epitaxial p-type substrates. In the literature, their performance has been individually characterized for quality assurance (QA) applications. The present study directly assessed and compared that of a MP512-bulk and that of a MP512-epitaxial in terms of radiation hardness, long-term …

Effect Of Cannabidiol On Muscarinic Neurotransmission In The Pre-Frontal Cortex And Hippocampus Of The Poly I:C Rat Model Of Schizophrenia, Carlos Jimenez Naranjo, Ashleigh L. Osborne, Katrina Weston-Green

Illawarra Health and Medical Research Institute

Cognitive impairment is a core symptom of schizophrenia; however, current antipsychotic drugs have limited efficacy to treat these symptoms and can cause serious side-effects, highlighting a need for novel therapeutics. Cannabidiol (CBD) is a non-intoxicating phytocannabinoid that has demonstrated pro-cognitive effects in multiple disease states, including a maternal immune activation (poly I:C) model of schizophrenia, but the mechanisms underlying the efficacy of CBD require investigation. Muscarinic neurotransmission is highly implicated in the cognitive impairments of schizophrenia; however, the effect of CBD on this system is unknown. We examined alterations in markers of muscarinic neurotransmission in the pre-frontal cortex (PFC) and …

Increased Tau Phosphorylation In Motor Neurons From Clinically Pure Sporadic Amyotrophic Lateral Sclerosis Patients, Claire H. Stevens, Natalie Guthrie, Marloes Van Roijen, Glenda M. Halliday, Lezanne Ooi

Illawarra Health and Medical Research Institute

Amyotrophic lateral sclerosis (ALS) is characterized by the progressive degeneration of motor neurons. There is a pathological and genetic link between ALS and frontotemporal lobar degeneration (FTLD). Although FTLD is characterized by abnormal phosphorylated tau deposition, it is unknown whether tau is phosphorylated in ALS motor neurons. Therefore, this study assessed tau epitopes that are commonly phosphorylated in FTLD, including serine 396 (pS396), 214 (pS214), and 404 (pS404) in motor neurons from clinically pure sporadic ALS cases compared with controls. In ALS lower motor neurons, tau pS396 was observed in the nucleus or the nucleus and cytoplasm. In ALS upper …

The Use Of Primary Care Electronic Health Records For Research: Lipid Medications And Mortality In Elderly Patients, Adam J. Hodgkins, Judy Mullan, Darren J. Mayne, Andrew D. Bonney

Illawarra Health and Medical Research Institute

General practice electronic health record (EHR) data have significant potential for clinical research. This study demonstrates the feasibility of utilising longitudinal EHR data analysis to address clinically relevant outcomes and uses the relationship between lipid medication prescription and all-cause mortality in the elderly as an exemplar for the validity of this methodology. EHR data were analysed to describe the association of lipid medication use, non-use or cessation with all-cause mortality in patients aged ≥75 years. Survival analysis with Cox regression was used to calculate hazard ratios, which were adjusted for confounders. There was no significant difference in all-cause mortality among …

Α-Conotoxin Vc1.1 Structure-Activity Relationship At The Human Α9Α10 Nicotinic Acetylcholine Receptor Investigated By Minimal Side Chain Replacement, Xin Chu, Han Shen Tae, Qingliang Xu, Tao Jiang, David J. Adams, Rilei Yu

Illawarra Health and Medical Research Institute

α-Conotoxin Vc1.1 inhibits the nicotinic acetylcholine receptor (nAChR) α9α10 subtype and has the potential to treat neuropathic chronic pain. To date, the crystal structure of Vc1.1-bound α9α10 nAChR remains unavailable; thus, understanding the structure–activity relationship of Vc1.1 with the α9α10 nAChR remains challenging. In this study, the Vc1.1 side chains were minimally modified to avoid introducing large local conformation perturbation to the interactions between Vc1.1 and α9α10 nAChR. The results suggest that the hydroxyl group of Vc1.1, Y10, forms a hydrogen bond with the carbonyl group of α9 N107 and a hydrogen bond donor is required. However, Vc1.1 S4 is …

The Drivers Of Antibiotic Use And Misuse: The Development And Investigation Of A Theory Driven Community Measure, Mitchell K. Byrne, Sebastien R. Miellet, Anica Mcglinn, Janaye Fish, Shahla Meedya, Nina Reynolds, Antoine M. Van Oijen

Illawarra Health and Medical Research Institute

BACKGROUND: Antimicrobial resistance is a global public health concern, with extensive associated health and economic implications. Actions to slow and contain the development of resistance are imperative. Despite the fact that overuse and misuse of antibiotics are highlighted as major contributing factors to this resistance, no sufficiently validated measures aiming to investigate the drivers behind consumer behaviour amongst the general population are available. The objective of this study was to develop and investigate the psychometric properties of an original, novel and multiple-item questionnaire, informed by the Theory of Planned Behaviour, to measure factors contributing to self-reported antibiotic use within the …

Molecular Processes Implicated In Human Age-Related Nuclear Cataract, Roger J. W Truscott, Michael G. Friedrich

Illawarra Health and Medical Research Institute

Human age-related nuclear cataract is commonly characterized by four biochemical features that involve modifications to the structural proteins that constitute the bulk of the lens: coloration, oxidation, insolubility, and covalent cross-linking. Each of these is progressive and increases as the cataract worsens. Significant progress has been made in understanding the origin of the factors that underpin the loss of lens transparency. Of these four hallmarks of cataract, it is protein-protein cross-linking that has been the most intransigent, and it is only recently, with the advent of proteomic methodology, that mechanisms are being elucidated. A diverse range of cross-linking processes involving …

Exploring The Geography Of Serious Mental Illness And Type 2 Diabetes Comorbidity In Illawarra-Shoalhaven, Australia (2010 -2017), Ramya Walsan, Darren J. Mayne, Nagesh B. Pai, Xiaoqi Feng, Andrew D. Bonney

Illawarra Health and Medical Research Institute

Objectives The primary aim of this study was to describe the geography of serious mental illness (SMI)-type 2 diabetes comorbidity (T2D) in the Illawarra-Shoalhaven region of NSW, Australia. The Secondary objective was to determine the geographic concordance if any, between the comorbidity and the single diagnosis of SMI and diabetes. Methods Spatial analytical techniques were applied to clinical data to explore the above objectives. The geographic variation in comorbidity was determined by Moran's I at the global level and the local clusters of significance were determined by Local Moran's I and spatial scan statistic. Choropleth hotspot maps and spatial scan …

Comparative Genetic Architectures Of Schizophrenia In East Asian And European Populations, Max Lam, Chia Chen, Zhiqiang Li, Alicia Martin, Julien Bryois, Xixian Ma, Helena Gaspar, Masashi Ikeda, Beben Benyamin, Brielin Brown, Ruize Liu, Wei Zhou, Lili Guan, Yoichiro Kamatani, Sung Kim, Michiaki Kubo, Agung A.A.A Kusumawardhani, Chih Liu, Hong Ma, Sathish Periyasamy, Atsushi Takahashi, Zhida Xu, Hao Yu, Feng Zhu, Wei Chen, Stephen Faraone, Stephen Glatt, Lin He, Steven Hyman, Hai Hwu, Steven Mccarroll, Benjamin M. Neale, Pamela Sklar, Dieter B. Wildenauer, Xin Yu, Dai Zhang, Bryan J. Mowry, Jimmy Lee, Peter A. Holmans, Shuhua Xu, Patrick Sullivan, Stephan Ripke, Michael O'Donovan, Mark Daly, Shengying Qin, Pak Sham, Nakao Iwata, Kyung-Han Hong, Sibylle G. Schwab, Weihua Yue, Ming Tsuang, Jianjun Liu, Xiancang Ma, Rene S. Kahn, Yongyong Shi, Hailiang Huang

Illawarra Health and Medical Research Institute

Schizophrenia is a debilitating psychiatric disorder with approximately 1% lifetime risk globally. Large-scale schizophrenia genetic studies have reported primarily on European ancestry samples, potentially missing important biological insights. Here, we report the largest study to date of East Asian participants (22,778 schizophrenia cases and 35,362 controls), identifying 21 genome-wide-significant associations in 19 genetic loci. Common genetic variants that confer risk for schizophrenia have highly similar effects between East Asian and European ancestries (genetic correlation = 0.98 ± 0.03), indicating that the genetic basis of schizophrenia and its biology are broadly shared across populations. A fixed-effect meta-analysis including individuals from East …

Shining A Spotlight On Dna: Single-Molecule Methods To Visualise Dna, Gurleen Kaur, Jacob S. Lewis, Antoine M. Van Oijen

Illawarra Health and Medical Research Institute

The ability to watch single molecules of DNA has revolutionised how we study biological transactions concerning nucleic acids. Many strategies have been developed to manipulate DNA molecules to investigate mechanical properties, dynamics and protein-DNA interactions. Imaging methods using small molecules and protein-based probes to visualise DNA have propelled our understanding of complex biochemical reactions involving DNA. This review focuses on summarising some of the methodological developments made to visualise individual DNA molecules and discusses how these probes have been used in single-molecule biophysical assays.

Area-Level Walkability And The Geographic Distribution Of High Body Mass In Sydney, Australia: A Spatial Analysis Using The 45 And Up Study, Darren J. Mayne, Geoffrey Morgan, Bin Jalaludin, Adrian E. Bauman

Illawarra Health and Medical Research Institute

Improving the walkability of built environments to promote healthy lifestyles and reduce high body mass is increasingly considered in regional development plans. Walkability indexes have the potential to inform, benchmark and monitor these plans if they are associated with variation in body mass outcomes at spatial scales used for health and urban planning. We assessed relationships between area-level walkability and prevalence and geographic variation in overweight and obesity using an Australian population-based cohort comprising 92,157 Sydney respondents to the 45 and Up Study baseline survey between January 2006 and April 2009. Individual-level data on overweight and obesity were aggregated to …

Pharmacological Blockade Of The Cd39/Cd73 Pathway But Not Adenosine Receptors Augments Disease In A Humanized Mouse Model Of Graft-Versus-Host Disease, Nicholas Geraghty, Debbie Watson, Ronald Sluyter

Illawarra Health and Medical Research Institute

Allogeneic hematopoietic stem cell transplantation is a curative therapy for a number of hematological malignancies, but is limited by the development of graft‐versus‐host disease (GVHD). CD39 and CD73 form an ectoenzymatic pathway that hydrolyzes extracellular adenosine 5′‐triphosphate (ATP) to adenosine, which respectively exacerbate or alleviate disease in allogeneic mouse models of GVHD. The current study aimed to explore the role of the CD39/CD73 pathway and adenosine receptor (AR) blockade in a humanized mouse model of GVHD. Immunodeficient nonobese diabetic‐severe combined immunodeficiency‐IL‐2 receptor γ^null mice were injected with human peripheral blood mononuclear cells, and subsequently injected with the CD39/CD73 antagonist …

Mutational Patterns In Metastatic Cutaneous Squamous Cell Carcinoma, Simon Mueller, Marie-Emilie A. Gauthier, Bruce G. Ashford, Ruta Gupta, Velimir Gayevskiy, Sydney Ch'ng, Carsten Palme, Kerwin Shannon, Jonathan Clark, Marie Ranson, Mark Cowley

Illawarra Health and Medical Research Institute

Cutaneous squamous cell carcinoma from the head and neck typically metastasize to the lymph nodes of the neck and parotid glands. When a primary is not identified, they are difficult to distinguish from metastases of mucosal origin and primary salivary gland squamous cell carcinoma. UV radiation causes a mutation pattern that predominantly features cytosine to thymine transitions at dipyrimidine sites and has been associated with cutaneous squamous cell carcinoma. In this study, we used whole genome sequencing data from 15 cutaneous squamous cell carcinoma metastases and show that a UV mutation signature is pervasive across the cohort and distinct from …

Geographic And Area-Level Socioeconomic Variation In Cardiometabolic Risk Factor Distribution: A Systematic Review Of The Literature, Renin Melkias Baby Selvi Toms, Andrew D. Bonney, Darren J. Mayne, Xiaoqi Feng, Ramya Walsan

Illawarra Health and Medical Research Institute

Introduction: A growing number of publications report variation in the distribution of cardiometabolic risk factors (CMRFs) at different geographic scales. A review of these variations may help inform policy and health service organisation.

Aim: To review studies reporting variation in the geographic distribution of CMRFs and its association with various proxy measures of area-level socioeconomic disadvantage (ASED) among the adult ( ≥ 18 years) population across the world.

Methods: A systematic search for published articles was conducted in four databases (MEDLINE (Ovid), PubMed, Scopus and Web of Science) considering the interdisciplinary nature of the review question. Population-based …

Association Of Camk2a Genetic Variants With Transition Time From Occasional To Regular Heroin Use In A Sample Of Heroin-Dependent Individuals, Antonia Eirich, Teresa Biermann, Christian Muller, Johannes Kornhuber, Beben Benyamin, Gary K. Hulse, Dieter B. Wildenauer, Sibylle G. Schwab

Illawarra Health and Medical Research Institute

Objectives: Susceptibility to heroin dependence is strongly influenced by genetic factors with heritability estimates as high as 0.7. A number of genes, as well as environmental factors, are likely to contribute to its etiology. Not all individuals who have ever tried heroin at some stage during their lifetime become dependent on heroin. It has been suggested that genetic factors might be more important in the transition stage to heroin dependence rather than in environmental exposures and experimenting with heroin. As the features of substance dependence and memory formation have been found to be strikingly similar, we have focused on …

Alterations To The Microbiota-Colon-Brain Axis In High-Fat-Diet-Induced Obese Mice Compared To Diet-Resistant Mice, Peng Zhang, Yinghua Yu, Yanfang Qin, Yuan Zhou, Renxian Tang, Qingling Wang, Xiangyang Li, Hongqin Wang, Katrina Weston-Green, Xu-Feng Huang, Kuiyang Zheng

Illawarra Health and Medical Research Institute

Obesity is underpinned by both genetic and environmental factors, including a high-saturated-fat diet. Some mice develop diet-induced obesity (DIO), but others remain diet resistant (DR) despite intake of the same high-saturated-fat diet, a phenomenon that mimics characteristics of the human obese phenotype. Microbiota-colon-brain axis regulation is important for energy metabolism and cognition. Using DIO and DR mouse models, this study aimed to examine gut microbiota, colonic inflammation and cognitive function to elucidate the role of microbiota-gut-brain regulation in DIO. C57Bl6/J mice fed a chronic saturated-palmitic-acid diet for 22 weeks showed significant body weight gain differences, with the top one third …

Radiofrequency Electromagnetic Field Exposure And Risk Perception: A Pilot Experimental Study, Berihun Zeleke, Chhavi Bhatt, Christopher Brzozek, Michael J. Abramson, Frederik Freudenstein, Rodney J. Croft, Peter M. Wiedemann, Geza P. Benke

Illawarra Health and Medical Research Institute

Background: Exposure to far-field radiofrequency electromagnetic fields (RF-EMF) has raised public concerns in recent decades. However, it is not known if individuals' perception towards the health risks of RF-EMF is dependent on their knowledge of the objectively measured personal RF-EMF exposure levels.

Objectives: This pilot study aimed to demonstrate the feasibility of objectively measuring personal RF-EMF exposure from mobile phone base stations (MPBS) and to determine if the risk perception of people to the potential health risk of exposure to RF-EMF from MPBS is dependent on their knowledge of personal RF-EMF exposure levels.

Design: An experimental study was conducted …

Investigating The Management Of Alcohol‐Related Presentations In An Australian Teaching Hospital, Siyu Qian, Mudar Irani, Renee M. Brighton, Wilfred W. Yeo, David Reid, Barbara L. Sinclair, Susan Bresnahan, Peter Lynch, Xiaoqi Feng, Ping Yu

Illawarra Health and Medical Research Institute

Introduction and Aims: Alcohol‐related morbidity is estimated to range from 10-38% of the presentations to hospital emergency departments. This study aims to investigate the actual management process for alcohol‐related presentations in a teaching hospital in Australia.

Design and Methods: Retrospective audit was conducted on the electronic medical records of 210 presentations with a primary or secondary diagnosis of 'alcohol use disorder' at discharge between November 2016 and February 2017. Six key management steps were investigated: identification of alcohol use disorder, documentation, thiamine, alcohol withdrawal assessment, benzodiazepine for alcohol withdrawal and referral to the drug and alcohol consultation liaison …

Towards An Accurate Prediction Of Nitrogen Chemical Shifts By Density Functional Theory And Gauge-Including Atomic Orbital, Peng Gao, Xingyong Wang, Haibo Yu

Illawarra Health and Medical Research Institute

An effcient, yet accurate, computational protocol for predicting nitrogen NMR chemical shifts based on density functional theory and the gauge-including atomic orbital approach has been proposed. A database of small and relatively rigid compounds containing nitrogen atoms was compiled. Scaling factors for the linear correlation between experimental ¹⁵N chemical shifts and calculated isotropic shielding constants have been systematically investigated with seven different levels of theory in both chloroform and dimethyl sulfoxide, two commonly used solvents for NMR experiments. The best method yields a root-mean-square deviation of about 5.30 ppm and 7.00 ppm in CHCl₃ and DMSO, respectively. Moreover, …

Reaction Of Ionised Steryl Esters With Ozone In The Gas Phase, Sarah E. Hancock, Alan T. Maccarone, Berwyck L. J Poad, Adam J. Trevitt, Todd W. Mitchell, Stephen J. Blanksby

Illawarra Health and Medical Research Institute

Cholesterol is an ubiquitous membrane lipid, that also serves as a precursor to many steroid hormones. The 5,6 carbon-carbon double bond on the tetracyclic carbon backbone of cholesterol is an attractive target for ozone with the reaction giving rise to a wide range of possibly bioactive molecules. Despite this, little is known about the ozonolysis of cholesterol esters, which often possess an additional double bond(s) on the fatty acyl chain. Understanding the intrinsic gas phase reaction of ozone with the two disparate double bond positions on cholesteryl esters can inform our understanding of these processes in vivo, particularly reactions occurring …

Tissue Equivalence Of Diamond For Heavy Charged Particles, Jeremy A. Davis, Peter Lazarakis, James Vohradsky, Michael L. F Lerch, Marco Petasecca, Susanna Guatelli, Anatoly B. Rosenfeld

Illawarra Health and Medical Research Institute

A dedicated Geant4 study was developed to determine a correction factor (C) to convert the energy deposition response in diamond to water for heavy charged ions, with atomic number (Z) greater than 2 with energies typical of Galactic Cosmic Rays. The energy deposition response within an ideal diamond based microdosimeter was modelled and converted into a microdosimetric spectrum. The simulation was then repeated, substituting diamond with water. It was shown that by applying the correction factor, the energy deposition and microdosimetric response in diamond could be matched to that of water. The correction factor was determined to be C = …