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Glasson J.,LBT Innovations Ltd | Hill R.,University of Adelaide | Summerford M.,LBT Innovations Ltd | Giglio S.,Healthscope Pathology
Journal of Clinical Microbiology | Year: 2016

While advancements have been made in some areas of pathology with diagnostic materials being screened using image analysis technologies, the reporting of cultures from agar plates remains a manual process. We compared the results for 2,163 urine cultures read by a reference panel of microbiologists, by the routine laboratory process, and by an automated plate reading system, APAS (LBT Innovations Ltd., South Australia). APAS detected colonies with a sensitivity of 99.1% and a specificity of 99.3% on blood agar, while on MacConkey agar, the colony detection sensitivity was 99.4% with a specificity of 99.3%. The device's ability to enumerate growth had an accuracy of 89.2%, and the morphological identification of colonies showed a high level of performance for the colony types typical of Escherichia coli and other enteric bacilli. On blood agar, lactose-fermenting colonies were morphologically identified with a sensitivity of 98.9%, while on MacConkey agar they were identified with a sensitivity of 99.2%. In this first clinical evaluation, APAS demonstrated high performance in the detection, enumeration, and colony classification of isolates compared with that for conventional plate-reading methods. The device found all cases reported by the laboratory and detected the most commonly encountered organisms found in urinary tract infections. Copyright © 2016 Mokhtari et al.


Singh A.B.,Deakin University | Singh A.B.,University of Melbourne | Bousman C.A.,University of Melbourne | Bousman C.A.,Swinburne University of Technology | And 7 more authors.
Translational Psychiatry | Year: 2012

The ATP-binding cassette family of transporter proteins, subfamily B (MDR/TAP), member 1 (ABCB1) (P-glycoprotein) transporter is a key component of the blood-brain barrier. Many antidepressants are subject to ABCB1 efflux. Functional polymorphisms of ABCB1 may influence central nervous system bioavailability of antidepressants subject to efflux. Single-nucleotide polymorphisms (SNPs) at rs1045642 (C3435T) of ABCB1 have been associated with efflux pump efficiency. This may explain part of the interindividual variation in antidepressant dose needed to remit. Individuals (N113) with DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) major depressive disorder (MDD) were treated with escitalopram (ESC) or venlafaxine (VEN) over 8 weeks. The17-item Hamilton Depression Rating Scale was assessed serially, blind to genotype. SNP rs1045642 of ABCB1 along with two SNPs previously reported to be in linkage disequilibrium with it (rs2032582 and rs1128503) were genotyped. Demographic features, clinical features, P450 metabolizer status and 5-HTTLPR (serotonin-transporter-linked promoter region) genotype were controlled for. Carriers of rs1045642 TT needed on average 11 mg of ESC to remit, whereas TC and CC carriers required 24 and 19 mg, respectively (P<0.0001). This equates to a 2.0-(95% confidence interval1.5-3.4; P<0.001) fold greater ESC dose needed to remit for C carriers compared with TT carriers at rs1045642. Of VEN-treated subjects carrying TT genotype at rs1045642, 73.3% remitted compared with 12.5% for CC genotype (odds ratio6.69; 95% confidence interval1.72-25.9, P<0.006). These data suggest that antidepressant dose needed to remit can be predicted by an ABCB1 SNP. This has the potential clinical translation implications for dose selection and remission from MDD. © 2012 Macmillan Publishers Limited All rights reserved.


Singh A.B.,Deakin University | Singh A.B.,University of Melbourne | Bousman C.A.,University of Melbourne | Bousman C.A.,Florey Institute for Neuroscience and Mental Health | And 7 more authors.
International Clinical Psychopharmacology | Year: 2013

Predicting differential antidepressant efficacy remains an elusive goal in major depressive disorder (MDD). The aims of this study were three-fold. Firstly, to examine if psychomotor retardation symptoms (item 8 on the 17-item Hamilton Depression Rating Scale) improve preferentially to venlafaxine (VEN) over escitalopram (ESC) treatment. Secondly, whether the 18 item CORE psychomotor signs scale predicted antidepressant remission. Finally, to investigate the role of two norepinephrine transporter gene (NET) polymorphisms (rs2242446 and rs5569) on antidepressant efficacy. Adults with Diagnostic and Statistical Manual of Mental Disorders, 4th ed. MDD (n=113) were treated with ESC or VEN prospectively for 8 weeks and rated serially with the Hamilton Depression Rating Scale. In a subsample (n=51) of patients from one of the three recruitment sites, the CORE psychomotor signs scale was also administered at baseline. Participants treated with VEN had significantly greater reduction in psychomotor retardation symptoms than those treated with ESC. The CORE scale did not predict antidepressant response or remission. Neither NET polymorphism moderated antidepressant efficacy. Findings suggest possible preferential utility of a selective serotonin and noradrenaline reuptake inhibitor in cases of MDD presenting with greater psychomotor retardation. The moderate to small sample size makes a type II error risk possible, and the negative findings need to be interpreted with caution. The positive finding of preferential efficacy of VEN for psychomotor retardation symptoms has potential translational utility. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


PubMed | Healthscope Pathology, University of Adelaide and LBT Innovations Ltd.
Type: Journal Article | Journal: Journal of clinical microbiology | Year: 2016

While advancements have been made in some areas of pathology with diagnostic materials being screened using image analysis technologies, the reporting of cultures from agar plates remains a manual process. We compared the results for 2,163 urine cultures read by a reference panel of microbiologists, by the routine laboratory process, and by an automated plate reading system, APAS (LBT Innovations Ltd., South Australia). APAS detected colonies with a sensitivity of 99.1% and a specificity of 99.3% on blood agar, while on MacConkey agar, the colony detection sensitivity was 99.4% with a specificity of 99.3%. The devices ability to enumerate growth had an accuracy of 89.2%, and the morphological identification of colonies showed a high level of performance for the colony types typical of Escherichia coli and other enteric bacilli. On blood agar, lactose-fermenting colonies were morphologically identified with a sensitivity of 98.9%, while on MacConkey agar they were identified with a sensitivity of 99.2%. In this first clinical evaluation, APAS demonstrated high performance in the detection, enumeration, and colony classification of isolates compared with that for conventional plate-reading methods. The device found all cases reported by the laboratory and detected the most commonly encountered organisms found in urinary tract infections.


Watson S.B.,Environment Canada | Monis P.,South Australian Water Corporation | Baker P.,South Australian Water Corporation | Giglio S.,Healthscope Pathology
Harmful Algae | Year: 2016

Cyanobacteria are one of the principal sources of volatile organic compounds (VOCs) which cause offensive taste and odor (T&O) in drinking and recreational water, fish, shellfish and other seafood. Although non-toxic to humans, these T&O compounds severely undermine public trust in these commodities, resulting in substantial costs in treatment, and lost revenue to drinking water, aquaculture, food and beverage and tourist/hospitality industries. Mitigation and control have been hindered by the complexity of the communities and processes which produce and modify T&O events, making it difficult to source-track the major producer(s) and the factors governing VOC production and fate. Over the past decade, however, advances in bioinformatics, enzymology, and applied detection technologies have greatly enhanced our understanding of the pathways, the enzymes and the genetic coding for some of the most problematic VOCs produced by cyanobacteria. This has led to the development of tools for rapid and sensitive detection and monitoring for the VOC production at source, and provided the basis for further diagnostics of endogenous and exogenous controls. This review provides an overview of current knowledge of the major cyanobacterial VOCs, the producers, the biochemistry and the genetics and highlight the current applications and further research needs in this area. © 2016 Elsevier B.V.


PubMed | South Australian Water Corporation, Environment Canada and Healthscope Pathology
Type: | Journal: Harmful algae | Year: 2017

Cyanobacteria are one of the principal sources of volatile organic compounds (VOCs) which cause offensive taste and odor (T&O) in drinking and recreational water, fish, shellfish and other seafood. Although non-toxic to humans, these T&O compounds severely undermine public trust in these commodities, resulting in substantial costs in treatment, and lost revenue to drinking water, aquaculture, food and beverage and tourist/hospitality industries. Mitigation and control have been hindered by the complexity of the communities and processes which produce and modify T&O events, making it difficult to source-track the major producer(s) and the factors governing VOC production and fate. Over the past decade, however, advances in bioinformatics, enzymology, and applied detection technologies have greatly enhanced our understanding of the pathways, the enzymes and the genetic coding for some of the most problematic VOCs produced by cyanobacteria. This has led to the development of tools for rapid and sensitive detection and monitoring for the VOC production at source, and provided the basis for further diagnostics of endogenous and exogenous controls. This review provides an overview of current knowledge of the major cyanobacterial VOCs, the producers, the biochemistry and the genetics and highlight the current applications and further research needs in this area.


PubMed | Healthscope Pathology, Limbach Laboratories, Roche Holding AG, Meander Medisch Centrum and Southern IML Pathology
Type: Evaluation Studies | Journal: Journal of clinical laboratory analysis | Year: 2016

The Roche Elecsys Vitamin D Total competitive protein-binding assay uses recombinant vitamin D binding protein for measuring 25-hydroxyvitamin D (25-OHD), which is different from commonly used antibody assays.The assay, standardized against LC-MS/MS, was tested at four sites. Evaluation included precision; between-laboratory variability; functional sensitivity; correlation to LC-MS/MS, HPLC, and immunoassays; as well as robustness, traceability, and EQAS performance.Precision testing showed within-run coefficient of variations (CVs) of 7%, within-laboratory CVs of <9.5%, between-laboratory precision CVs of 10.1%, and a functional sensitivity below 9.8 nmol/l (at CV 12.9%). The assay showed equivalent 25-OHD levels for matched serum and plasma samples, good reagent lot-to-lot consistency in pooled sera over time, and good agreement with HPLC (relative bias -8.8%). Comparison with LC-MS/MS methods yielded relative biases of -15.4, -13.5, -10.2, and 3.2%. Comparison against immunoassays showed a relative bias of 14.5% (DiaSorin Liaison) and -58.2% (IDS-iSYS). The overall mean results in 2 years DEQAS was 102% of the ALTM. In a certified reference patient panel, the average bias was < 4% for the sum of 25-OHD2 and 25-OHD3.The Elecsys Vitamin D Total assay demonstrated good overall performance and is, according to present standards, very suitable for automated measurement of 25-OHD.


Houssami N.,University of Sydney | MacAskill P.,University of Sydney | Balleine R.L.,University of Sydney | Bilous M.,Healthscope Pathology | Pegram M.D.,University of Miami
Breast Cancer Research and Treatment | Year: 2011

The proto-oncogene, HER2, has prognostic and predictive relevance in invasive breast cancer (IBC). HER2 testing of primary IBC guides treatment selection and is assumed to reflect HER2 status of associated metastases, although HER2 discordance between IBC and metastasis has been reported. Systematic review and meta-analysis of HER2 status in IBC and its paired loco-regional or distant metastasis were done. Quality appraisal considered whether (within-subject) testing conditions were maintained for paired primary and metastasis. Random effects logistic regression models were used to estimate pooled within-subject HER2 discordant proportions and to examine study-level covariates, including tumor-related and testing-related variables, potentially associated with HER2 discordance differences across (between) studies. Modelled paired HER2 data for primary and metastatic cancer (2520 subjects, 26 studies) showed a pooled HER2 discordance of 5.5% (3.6-8.5%). Sensitivity analysis, excluding the only study not maintaining same conditions for paired testing, gave a pooled estimate of 5.2% (3.5-7.8%). Pooled discordant proportion was not associated with differences between studies in test type, test scoring or interpretation criteria, subjects' median age, study time-frame, or HER2 positivity in primary cancer (all P > 0.05). However, type of metastasis was significantly associated with estimated HER2 discordance (P = 0.0017): studies of primary tumor paired with distant metastases had higher discordance [11.5% (6.9-18.6%)] than studies of primary paired with lymph node metastases only [4.1% (2.4-7.2%)], or those paired with nodal or various metastases [3.3% (2.0-5.6%)]; P < 0.01. HER2 discordant proportion was higher where paired metastases were metachronous relative to synchronous to primary IBC (P = 0.0024). Sensitivity analysis provided weak evidence (P = 0.074) that discordance in the direction of change from HER2-negative primary cancer to HER2-positive paired metastasis was more likely than the reverse. Study-level meta-analysis suggests factors associated with the type of metastasis as underlying mechanisms for observed HER2 discordance between primary IBC and paired metastasis. Test-related factors did not account for differences across studies in the HER2 discordant proportion. © 2011 Springer Science+Business Media, LLC.


Pathmanathan N.,Westmead Hospital | Pathmanathan N.,University of Sydney | Michael Bilous A.,Healthscope Pathology
Pathology | Year: 2012

Testing for HER2 positivity in breast cancer carries implications for prognosis and therapeutic response in patients. In recent times there have been numerous developments and refinements in the available technologies for HER2 testing. In addition to this, guidelines have been developed and modified in an attempt to improve reliability and accuracy of testing. Immunohistochemistry and FISH testing have been the most widely used methodology, and the technique which has the largest knowledge base. Some of the inherent disadvantages have prompted the development of newer brightfield techniques which overcome some of these issues. There is gathering experience with these emerging technologies. Despite efforts to optimise and standardise procedures there remains a small percentage of cases that continue to be unresolved, whether this be due to issues of polysomy of chromosome 17, other complex genetic changes or analytical/ interpretative issues. An ideal method for the resolution of these equivocal results should be considered in a specialised testing/referral centre, and this may include karyotyping studies of chromosome 17 or multiple probes for chromosome 17 using fluorescence in situ hybridisation or multiplex ligation-dependent probe amplification. It is timely to review of some of the newer techniques available for routine testing and approaches for cases which prove difficult to resolve using conventional testing methodology. © 2012 Royal College of Pathologists of Australasia.


Wilson R.,Healthscope Pathology | Beerbaum P.,Healthscope Pathology | Giglio S.,Healthscope Pathology
Letters in Applied Microbiology | Year: 2015

A total of 274 samples were screened for toxigenic Clostridium difficile using a combination of several commercially available assays, and positive isolates ribotyped. A two-step algorithm assisted in demonstrating an increased prevalence of C. difficile infection in South Australia of 9·8%, most of which were ribotypes 014 and 052. A glutamate dehydrogenase assay followed by the detection of genes associated with toxin production was the most sensitive and specific algorithm for screening for toxigenic C. difficile. Significance and Impact of the Study: Rapid and accurate detection of toxigenic Clostridium difficile is important for the diagnosis of C. difficile colitis and the management of patients in healthcare institutions to minimize the spread of disease. A critical review of currently available commercial methods supports a recommendation for a 2-step algorithm that is relatively inexpensive and amenable to the routine pathology laboratory. It is anticipated that the detection of C. difficile will increase with improved detection methods, and the ribotype prevalence presented in this manuscript will be useful for any current and future source tracking purposes. Significance and Impact of the Study: Rapid and accurate detection of toxigenic Clostridium difficile is important for the diagnosis of C. difficile colitis and the management of patients in healthcare institutions to minimize the spread of disease. A critical review of currently available commercial methods supports a recommendation for a 2-step algorithm that is relatively inexpensive and amenable to the routine pathology laboratory. It is anticipated that the detection of C. difficile will increase with improved detection methods, and the ribotype prevalence presented in this manuscript will be useful for any current and future source tracking purposes. © 2014 The Society for Applied Microbiology.

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