ORCID Profile
0000-0001-6654-0278
Current Organisation
Peter MacCallum Cancer Centre
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Publisher: Wiley
Date: 18-02-2022
DOI: 10.1002/JMRS.570
Abstract: The use of ionising radiation results in occupational exposure to medical imaging professionals, requiring routine monitoring. This study aims to assess the effect of increased utilisation of mobile X‐ray units, mobile imaging of non‐routine body regions and radiographer work practice changes for impact on staff radiation dose during the early stages of the COVID‐19 pandemic. A retrospective analysis of general radiology departments across two metropolitan hospitals was performed. Personal radiation monitor exposure reports between January 2019 and December 2020 were analysed. Statistical analysis was conducted using a Mann–Whitney U test when comparing each quarter, from 2019 to 2020. Categorical data were compared using a Chi‐squared test. Mobile X‐ray use during the pandemic increased approximately 1.7‐fold, with the peak usage observed in September 2020. The mobile imaging rate per month of non‐routine body regions increased from approximately 6.0–7.8%. Reported doses marginally increased during Q2, Q3 and Q4 of 2020 (in comparison to 2019 data), though was not statistically significant (Q2: P = 0.13 Q3: P = 0.31 and Q4 P = 0.32). In Q1, doses marginally decreased and were not statistically significant ( P = 0.22). Increased utilisation and work practice changes had no significant effect on reported staff radiation dose. The average reported dose remained significantly lower than the occupational dose limits for radiation workers of 20 mSv.
Publisher: CSIRO Publishing
Date: 2012
DOI: 10.1071/CH12140
Abstract: The thiazolidinedione, compound 1, has previously shown pan-inhibition of the phosphoinositide 3-kinase (PI3K) class I isoforms. We hypothesized the derivatization of the thiazolidinedione core of compound 1 could introduce isoform selectivity. We report the synthesis, characterization, and inhibitory activity of a novel series of 4-iminothiazolidin-2-ones for inhibition of the class I PI3K isoforms. Their synthesis was successfully achieved by multiple pathways described in this paper. Initial in vitro data of 28 analogues demonstrated poor inhibition of all class I PI3K isoforms. However, we identified an alternate target, the phosphodiesterases, and present preliminary screening results showing improved inhibitory activity.
Publisher: Wiley
Date: 19-10-2023
DOI: 10.1002/JMRS.623
Abstract: Allied health assistants are support staff who assist medical imaging professionals in their clinical and non‐clinical role. Assistants can improve efficiency of medical imaging services however, little is known about the specific tasks they perform. A two‐phase explanatory, sequential mixed‐methods study design comprising a time motion survey and qualitative interviews was conducted across three health services in Victoria, Australia. Participants were medical imaging assistants supporting medical imaging professionals. Participants recorded tasks completed on a time motion proforma across two working days. Time spent on tasks was categorised into patient related and non‐patient related tasks. Semi‐structured interviews were conducted to explore assistants' perspectives about tasks, their roles and any responsibilities. Time motion data was descriptively analysed. Qualitative data were audiotaped, transcribed verbatim and analysed using the framework analysis method. Quantitative and qualitative findings were integrated using data triangulation. Four medical imaging assistants participated, providing 4170 min of time motion data and 138 min of interview data. Integration of time motion and interview data revealed the medical imaging assistant role is predominantly non‐patient facing autonomous and critical to workflow erse and requires flexibility has the potential to expand into a more patient‐facing role. Medical imaging assistants make significant contributions to workflow management. Their role is predominantly non‐patient facing but there appear opportunities for the clinical role to expand. Realizing these opportunities will require careful consideration of the challenges and benefits of extending their scope of practice.
Publisher: American Chemical Society (ACS)
Date: 08-09-2015
DOI: 10.1021/ACS.CHEMRESTOX.5B00202
Abstract: Drug-induced toxicity is a leading cause of drug withdrawal from clinical development and clinical use and represents a major impediment to the development of new drugs. The mechanisms underlying drug-induced toxicities are varied however, metabolic bioactivation to form reactive metabolites has been identified as a major contributor.1,2 These electrophilic species can covalently modify important biological macromolecules and thereby increase the risk of adverse drug reactions or idiosyncratic toxicity. Consequently, screening compounds for their propensity to form reactive metabolites has become an integral part of drug discovery programs. This screening process typically involves identification of structural alerts as well as the generation of reactive metabolites in vitro in subcellular hepatic fractions, followed by trapping the reactive species with nucleophiles and characterization via LC-MS. This article presents evidence for the bioactivation of a series of aminopyrazole derivatives via LC-MS detection of glutathione ethyl ester-trapped reactive intermediates formed in human liver microsomal incubations. These results indicate that the aminopyrazole motif, within specific contexts, may be considered a new structural alert for the potential formation of reactive metabolites.
Publisher: American Chemical Society (ACS)
Date: 31-12-2012
DOI: 10.1021/ML300336J
Publisher: Elsevier BV
Date: 02-2010
DOI: 10.1016/J.CHEMBIOL.2010.02.001
Abstract: PI3 kinase inhibitors are hot property. In this issue of Chemistry & Biology, Williams et al. add a dual PI3Kdelta/gamma inhibitor to the collection and show that its anti-inflammatory profile in vitro is quite different from pan-PI3K inhibitors, but bears an uncanny resemblance to that of the glucocorticoid drugs.
Publisher: MDPI AG
Date: 30-03-2023
DOI: 10.3390/MOLECULES28073103
Abstract: Human immunodeficiency virus type I (HIV-1) is a retrovirus that infects cells of the host’s immune system leading to acquired immunodeficiency syndrome and potentially death. Although treatments are available to prevent its progression, HIV-1 remains a major burden on health resources worldwide. Continued emergence of drug-resistance mutations drives the need for novel drugs that can inhibit HIV-1 replication through new pathways. The viral protein reverse transcriptase (RT) plays a fundamental role in the HIV-1 replication cycle, and multiple approved medications target this enzyme. In this study, fragment-based drug discovery was used to optimize a previously identified hit fragment (compound B-1), which bound RT at a novel site. Three series of compounds were synthesized and evaluated for their HIV-1 RT binding and inhibition. These series were designed to investigate different vectors around the initial hit in an attempt to improve inhibitory activity against RT. Our results show that the 4-position of the core scaffold is important for binding of the fragment to RT, and a lead compound with a cyclopropyl substitution was selected and further investigated. Requirements for binding to the NNRTI-binding pocket (NNIBP) and a novel adjacent site were investigated, with lead compound 27—a minimal but efficient NNRTI—offering a starting site for the development of novel dual NNIBP-Adjacent site inhibitors.
Publisher: Wiley
Date: 19-09-2020
DOI: 10.1002/SONO.12238
Publisher: Springer Science and Business Media LLC
Date: 25-03-2022
DOI: 10.1038/S41467-022-29234-3
Abstract: The emergence of multidrug-resistant (MDR) Gram-negative pathogens is an urgent global medical challenge. The old polymyxin lipopeptide antibiotics (polymyxin B and colistin) are often the only therapeutic option due to resistance to all other classes of antibiotics and the lean antibiotic drug development pipeline. However, polymyxin B and colistin suffer from major issues in safety (dose-limiting nephrotoxicity, acute toxicity), pharmacokinetics (poor exposure in the lungs) and efficacy (negligible activity against pulmonary infections) that have severely limited their clinical utility. Here we employ chemical biology to systematically optimize multiple non-conserved positions in the polymyxin scaffold, and successfully disconnect the therapeutic efficacy from the toxicity to develop a new synthetic lipopeptide, structurally and pharmacologically distinct from polymyxin B and colistin. This resulted in the clinical candidate F365 ( QPX9003 ) with superior safety and efficacy against lung infections caused by top-priority MDR pathogens Pseudomonas aeruginosa , Acinetobacter baumannii and Klebsiella pneumoniae .
Publisher: Elsevier BV
Date: 02-2013
DOI: 10.1016/J.BMCL.2012.11.076
Abstract: Phosphoinositide 3-kinases (PI3K) hold significant therapeutic potential as novel targets for the treatment of cancer. ZSTK474 (4a) is a potent, pan-PI3K inhibitor currently under clinical evaluation for the treatment of cancer. Structural studies have shown that derivatisation at the 5- or 6-position of the benzimidazole ring may influence potency and isoform selectivity. However, synthesis of these derivatives by the traditional route results in a mixture of the two regioisomers. We have developed a straightforward regioselective synthesis that gave convenient access to 5- and 6-methoxysubstituted benzimidazole derivatives of ZSTK474. While 5-methoxy substitution abolished activity at all isoforms, the 6-methoxy substitution is consistently 10-fold more potent. This synthesis will allow convenient access to further 6-position derivatives, thus allowing the full scope of the structure-activity relationships of ZSTK474 to be probed.
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.BMCL.2016.08.028
Abstract: A series of PI3Kδ inhibitors derived from the pan-PI3K inhibitor ZSTK474 was prepared that target a non-conserved region of the catalytic site. Dependent upon the substituents present, these analogues show different levels of isoform selectivity and sensitivity to the mutation N836D in PI3Kδ. As a marker of 'on-target' activity and permeability, a selection of the most potent PI3Kδ inhibitors were shown to inhibit pAkt production in the Nawalma Burkitt lymphoma cell line.
Publisher: Springer Science and Business Media LLC
Date: 24-10-2022
DOI: 10.1186/S12913-022-08642-7
Abstract: Allied health assistants (AHAs) are support staff who complete patient and non-patient related tasks under the delegation of an allied health professional. Delegating patient related tasks to AHAs can benefit patients and allied health professionals. However, it is unclear whether the AHA workforce is utilised optimally in the provision of patient care. The purpose of this study was to determine the proportion of time AHAs spend on patient related tasks during their working day and any differences across level of AHA experience, clinical setting, and profession delegating the task. A time motion study was conducted using a self-report, task predominance work s ling method. AHAs were recruited from four publicly-funded health organisations in Victoria, Australia. AHAs worked with dietitians, occupational therapists, physiotherapists, podiatrists, social workers, speech pathologists, psychologists, and exercise physiologists. The primary outcome was quantity of time spent by AHAs on in idual task-categories. Tasks were grouped into two main categories: patient or non-patient related activities. Data were collected from July 2020 to May 2021 using an activity capture proforma specifically designed for this study. Logistic mixed-models were used to investigate the extent to which level of experience, setting, and delegating profession were associated with time spent on patient related tasks. Data from 51 AHAs showed that AHAs spent more time on patient related tasks (293 min/day, 64%) than non-patient related tasks (167 min/day, 36%). Time spent in community settings had lower odds of being delegated to patient related tasks than time in the acute hospital setting (OR 0.44, 95%CI 0.28 to 0.69, P 0.001). Time delegated by exercise physiologists and dietitians was more likely to involve patient related tasks than time delegated by physiotherapists (exercise physiology: OR 3.77, 95% 1.90 to 7.70, P 0.001 dietetics: OR 2.60, 95%CI 1.40 to 1.90, P = 0.003). Time delegated by other professions (e.g. podiatry, psychology) had lower odds of involving patient related tasks than physiotherapy (OR 0.37, 95%CI 0.16 to 0.85, P = 0.02). AHAs may be underutilised in community settings, and by podiatrists and psychologists. These areas may be targeted to understand appropriateness of task delegation to optimise AHAs’ role in providing patient care.
Publisher: Wiley
Date: 04-01-2011
Abstract: A series of synthesized and commercially available compounds were assessed against PI3Kα for in vitro inhibitory activity and the results compared to binding calculated in silico. Using published crystal structures of PI3Kγ and PI3Kδ co‐crystallized with inhibitors as a template, docking was able to identify the majority of potent inhibitors from a decoy set of 1000 compounds. On the other hand, PI3Kα in the apo‐form, modeled by induced fit docking, or built as a homology model gave only poor results. A PI3Kα homology model derived from a ligand‐bound PI3Kδ crystal structure was developed that has a good ability to identify active compounds. The docking results identified binding poses for active compounds that differ from those identified to date and can contribute to our understanding of structure–activity relationships for PI3K inhibitors.
Publisher: Wiley
Date: 04-04-2013
Publisher: Hindawi Limited
Date: 10-06-2022
DOI: 10.1111/HSC.13874
Abstract: Allied health assistants (AHAs) are important members of the health workforce and key to meeting population health needs. Previous studies exploring the role and utility of AHAs from multiple stakeholder perspectives suggest AHAs remain poorly utilised in many healthcare settings. This qualitative study explores the experiences and perspectives of AHAs working in healthcare settings to determine the contextual factors influencing their role, and mechanisms to maximise their utility. We conducted semi-structured interviews using purposive s ling with 21 AHAs, from one regional and three metropolitan health services in Australia, between February and July 2021. We used a team-based framework approach to analyse the data. Four major themes were identified: 1) AHAs' interpersonal relationships, 2), clarity and recognition of AHA roles and role boundaries, 3) AHAs accessing education and professional development, and 4) the professional identity of the AHA workforce. Underpinning each of these themes were relationships between AHAs and other healthcare professionals, their patients, health services, and the wider AHA workforce. This study may inform initiatives to optimise the utility of AHAs and increase their role in, and impact on, patient care. Such initiatives include the development and implementation of guidelines and competencies to enhance the clarity of AHAs' scope of practice, the establishment of standardised educational pathways for AHAs, and increased engagement with the AHA workforce to make decisions about their scope of practice. These initiatives may precede strategies to advance the AHA career structure.
Publisher: American Chemical Society (ACS)
Date: 26-07-2023
No related grants have been discovered for Jo-Anne Pinson.