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3. Australian atmospheric pressure and sea level data during the 2022 Hunga-Tonga Hunga-Ha’apai volcano tsunami

Author

Gareth Davies, Kaya Wilson, Ben Hague, Diana Greenslade, Daryl Metters, Paul Boswood, Sam Maddox, Sarah-Kate Dakin, Karen Palmer, Ben Galton-Fenzi, John French, and Claire Kain

Subjects
Science
Abstract

Abstract On January 15, 2022, an ongoing eruption at the Hunga-Tonga Hunga-Ha’apai volcano generated a large explosion which resulted in a globally observed tsunami and atmospheric pressure wave. This paper presents time series observations of the event from Australia including 503 mean sea level pressure (MSLP) sensors and 103 tide gauges. Data is provided in its original format, which varies between data providers, and a post-processed format with consistent file structure and time zone. High-pass filtered variants of the data are also provided to facilitate study of the pressure wave and tsunami. For a minority of tide gauges the raw sea level data cannot be provided, due to licence restrictions, but high-pass filtered data is always provided. The data provides an important historical record of the volcanic pressure wave and tsunami in Australia. It will be useful for research on atmospheric and ocean waves associated with large volcanic eruptions.

Published
2024
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4. Essential and virulence genes of Coxiella burnetii

Author

Metters, G., Titball, Richard, Norville, Isobel, and Hemsley, Claudia

Subjects
TraDIS, TnSeq, Transposon sequencing, Coxiella
Abstract

Coxiella burnetii is an intracellular pathogen responsible for causing Q fever in humans, which has been classified as a potential category B bioterrorism agent by the CDC. There is a requirement for the identification of possible drug and vaccine targets for C. burnetii due to the lack of a licenced vaccine in the UK, and lengthy drug regimens with undesirable side effects. Until the recent development of axenic media for C. burnetii, its obligate intracellular lifestyle has meant there is a paucity of information on the virulence mechanisms of C. burnetii. In this project the Galleria mellonella insect model was further characterised to aid its use in the identification of C. burnetii virulence determinants. It was found that in G. mellonella, C. burnetii proliferates quicker than in axenic media, and forms a vacuole comparable to that seen in mammalian cells. To identify essential and virulence determinants in a high-throughput manner, a transposon library containing > 10,000 unique transposon mutants was created. Axenic media was used to identify essential genes, and significant steps were taken in the use of G. mellonella as a screen for the high-throughput identification of virulence determinants. Finally, a transposon mutant in CBU_1468, a gene which confers a hypothetical protein of unknown function, was discovered to be attenuated in the G. mellonella model. Potentially identifying a further virulence factor and giving scope for further investigation.

Published
2022

7. An Examination of the Ming Empire's Inner Asianness: Focusing on Qing Dynasty Analogies.

Author

Zhong, Han and Phurbu Dorje Metters, Kevin

Abstract

Among overseas "New Qing History" scholars, the Ming Empire is typically interpreted as an ethnically Han-Chinese regime that lacked the characteristics of Inner Asian polities. This author, however, asserts that this view is incorrect. Like the Qing, the emperors of the Ming ruled as qaghans over their northern steppe subjects and as the incarnation of the bodhisattva Manjusri in the eyes of Tibetan-Mongolian Buddhists. Also like their Qing dynasty counterparts, the Ming Empire produced multilingual documents, combining Chinese and ethnic minority scripts, a potent symbol of their "universal" rule. Lastly, the Ming emperors also actively pursued a policy of promoting governance through religion, creating a cultural and political legacy that would come to directly shape later relations between the Qing empire and the frontier regions of their empire. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Pharmaceuticals: are you prepared for the 2D code sunrise?

Author

Metters, Lee and Cutforth, James

Subjects
Domino Printing Sciences PLC -- Product information, Printing industry -- Product information, Bar codes -- Product information, Business, Chemicals, plastics and rubber industries, Engineering and manufacturing industries, Business, international
Abstract

International standards organisation GS1 is preparing to transition away from 1D barcodes to a new 2D format, the GS1 Digital Link, with a push planned for 2027. Domino Printing Sciences [...]

Published
2024

9. An evaluation of a student-led career profiling project to support the exploration of a career in general practice and other specialties

Author

Hannah Gyekye-Mensah, Arabella Watkins, Joseph Wenden, Imogen Horn, Jemimah Beardwood, Melvyn Jones, and Emma Metters

Subjects
career choice, career guidance, general practice, medical students, Medicine (General), R5-920
Abstract

Background: Choosing medical careers is complex but the undergraduate period is formative. St George’s University of London (SGUL) students called for greater careers information. Aim: To develop and evaluate students’ careers resources. Design & setting: A quality improvement student–staff project at SGUL, UK. Method: A ‘Plan-Do-Study-Act’ (PDSA) cycle was completed. For the ‘Plan’ element, students’ career intentions and information preferences were surveyed. For the ‘Do’ element, video interviews with clinicians and infographic posters were produced and published on SGUL’s virtual learning environment. For the ‘Study’ element, feedback questionnaires were thematically analysed using Kirkpatrick’s framework. For the ‘Act’ element, the model was rolled out across SGUL programmes. Results: In the ‘Plan’ stage, 79 students ranked interest in specialties, with general practice being the second most popular. Students were unconfident in how to pursue careers and wanted more information. For the ‘Do’ element, 13 careers videos and infographics were created for 10 specialties. The ‘Study’ questionnaire showed changes across three of the four levels in Kirkpatrick’s model of evaluation of training. Level 1 (Response): students found resources helpful and accessible. Level 2 (Learning): students reported increased understanding of careers. Level 3 (Transfer): students planned using checklists and made career comparisons by specialty. Level 4 (Results): students’ career choices were not demonstrated, but there were tentative proxy measures such as copying and modelling career routes and choices. ‘Act’ involved rolling out and regularly updating resources. Conclusion: This PDSA model enabled development of resources by students mapped to students’ needs. Changes were demonstrated in relation to students’ response, learning, and transfer, with tentative suggestions of impact on career choice.

Published
2022
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11. Cooperative Lewis pairs in small molecule activation and dehydrocoupling of amine- and phosphine-boranes

Author

Metters, Owen J.

Subjects
547
Abstract

This thesis contains a diverse body of work based around the theme of Lewis acid/base chemistry. The reactivity of classical Lewis adducts, such as amine- and phosphine-boranes, has been investigated in addition to the more nascent field of frustrated Lewis pairs (FLPs). Chapter 1 contains a brief overview of the concept of Lewis acidity and basicity whilst also providing a survey of previous work relevant to this thesis. Chapter 2 reports a novel, modular synthetic route to intermolecular Zr/P FLPs with varying steric and electronic properties. The reactivity of these pairs with a plethora of small molecules has been assessed (H2, C02, Phenylacetylene, THF) and is found to be directly related to both the steric and electronic character of the Lewis acid and base employed. The results contained in Chapter 3 build. on those in Chapter 2. by applying the intermolecular Zr/P FLPs as catalysts for the dehydrocoupling of amineboranes. Initial insights into the mechanism of these dehydrocoupling reactions are also provided. Chapter 4 describes preliminary investigations into new directions for the field of transition metal FLP chemistry. Expansion of the intermolecular FLP paradigm to include alternate Lewis acids (Ti(IV) and Ti(III)) and Lewis bases (N-heterocyclic carbenes (NHCs)) has been attempted. Furthermore previously reported intramolecular ZrlP FLPs are shown to be active catalysts for the dehydrocoupling of primary and secondary phosphine-boranes. Finally Chapter 5 details an alternative approach to the synthesis of amine-borane dehydrocoupling products via the deprotonation of amineboronium cations and related species. This methodology has allowed for the synthesis of poly(N-methylaminoborane) in the absence of a transition metal catalyst, whilst also permitting the study of highly reactive primary aminoboranes (RNH=BH2, R = Me or Bu).

Published
2016

18. Coxiella burnetii replicates in Galleria mellonella hemocytes and transcriptome mapping reveals in vivo regulated genes

Author

Andrea Kovacs-Simon, Georgie Metters, Isobel Norville, Claudia Hemsley, and Richard W. Titball

Subjects
coxiella burnetii, galleria mellonella, t4ss, virulence, transcriptome profiling, Infectious and parasitic diseases, RC109-216
Abstract

Larvae of the greater wax moth (Galleria mellonella) are susceptible to infection with C. burnetii, an obligate intracellular bacterial pathogen. We show that bacteria are found in hemocytes after infection, and occupy vacuoles which are morphologically similar to Coxiella-containing vacuoles seen in infected mammalian phagocytes. We characterized the infection by transcriptome profiling of bacteria isolated from the hemocytes of infected larvae and identified 46 highly upregulated genes. The encoded proteins are predicted to be involved in translation, LPS biosynthesis, biotin synthesis, scavenging of reactive oxygen species, and included a T4SS effector and 30 hypothetical proteins. Some of these genes had previously been shown to be upregulated in buffalo green monkey (BGM) cells or in mice, whilst others appear to be regulated in a host-specific manner. Altogether, our results demonstrate the value of the G. mellonella model to study intracellular growth and identify potential virulence factors of C. burnetii.

Published
2020
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20. Designing and fabricating novel screen printed electrochemical configurations

Author

Metters, Jonathan Peter

Subjects
541
Abstract

This thesis reports the design and fabrication of novel never before reported screen printed electrochemical devices. Chapters 1 and 2 of this thesis give an overview of the relevant fundamental electrochemical concepts with which this thesis is concerned. Additionally Chapter 2 focuses on the technique of screen printing upon which this thesis is focused on with a detailed overview not only of the screen printing process, but also its current prevalence within the field of electrochemistry with particular attention paid towards the development of novel screen printed electrode configurations. Chapter 3 reports modified electrodes presenting the first examples of noble metal and carbon nanotube modified screen printed electrodes which are evaluated and benchmarked towards target analytes and the current literature. Again, simplification of analytical protocols is sought through the production of screen printed sensors using screen printing technology rather than alternative techniques such as drop-coating and electroplating. The final part of this thesis explores electrode geometry and substrate composition (described in Chapters 4 and 5) in order to impart improvements and greater understanding in the mass transport characteristics in order to lead to significant improvement in the electroanalytical sensing features of the devised sensors. In the case of substrate composition the role of the underlying substrate, a fundamental component concerning screen printing is explored with different potential substrate materials being trialled and compared to the commonly utilised polyester substrate with regards to the effects of mechanical force upon the electrochemical performance of the sensors.

Published
2013

22. Serialisation beyond compliance: the gateway to competitive differentiation: Product-level serialisation has historically been associated with compliance mandates in highly regulated industries such as pharmaceuticals, medical devices and tobacco; its central premise was to prevent counterfeit goods from entering these markets

Author

Metters, Lee

Subjects
Domino Printing Sciences PLC -- Marketing, Medical equipment -- Marketing, Physiological apparatus -- Marketing, Logistics, Product counterfeiting, Company marketing practices, Business, Chemicals, plastics and rubber industries, Engineering and manufacturing industries, Business, international
Abstract

However, as organisations within these sectors have realised, having full traceability within the supply chain offers benefits beyond compliance alone, providing opportunities for greater visibility, data exchange and information sharing [...]

Published
2023

23. Extreme water levels, waves and coastal impacts during a severe tropical cyclone in northeastern Australia: a case study for cross-sector data sharing

Author

T. R. Mortlock, D. Metters, J. Soderholm, J. Maher, S. B. Lee, G. Boughton, N. Stewart, E. Zavadil, and I. D. Goodwin

Subjects
Environmental technology. Sanitary engineering, TD1-1066, Geography. Anthropology. Recreation, Environmental sciences, GE1-350, Geology, QE1-996.5
Abstract

Severe tropical cyclone (TC) Debbie made landfall on the northern Queensland coast of Australia on 27 March 2017 after crossing the Great Barrier Reef as a slow-moving Category 4 system. Groups from industry, government and academia collected coastal hazard and impact data before, during and after the event and shared these data to produce a holistic picture of TC Debbie at the coast. Results showed the still water level exceeded the highest astronomical tide by almost a metre. Waves added a further 16 % to water levels along the open coast, and were probably unprecedented for this area since monitoring began. In most places, coastal barriers were not breached and as a result there was net offshore sand transport. If landfall had occurred 2 h earlier with the high tide, widespread inundation and overwash would have ensued. This paper provides a case study of effective cross-sector data sharing in a natural hazard context. It advocates for a shared information platform for coastal extremes in Australia to help improve the understanding and prediction of TC-related coastal hazards in the future.

Published
2018
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24. Macrophage infectivity potentiator protein, a peptidyl prolyl cis-trans isomerase, essential for Coxiella burnetii growth and pathogenesis

Author

Debowski, Aleksandra W., primary, Bzdyl, Nicole M., additional, Thomas, David R., additional, Scott, Nichollas E., additional, Jenkins, Christopher H., additional, Iwasaki, Jua, additional, Kibble, Emily A., additional, Khoo, Chen Ai, additional, Scheuplein, Nicolas J., additional, Seibel, Pamela M., additional, Lohr, Theresa, additional, Metters, Georgie, additional, Bond, Charles S., additional, Norville, Isobel H., additional, Stubbs, Keith A., additional, Harmer, Nicholas J., additional, Holzgrabe, Ulrike, additional, Newton, Hayley J., additional, and Sarkar-Tyson, Mitali, additional

Published
2023
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36. Macrophage infectivity potentiator protein, a peptidyl prolyl cis-trans isomerase, essential for Coxiella burnetii growth and pathogenesis

Author

Zamboni, DS, Debowski, AWW, Bzdyl, NMM, Thomas, DRR, Scott, NEE, Jenkins, CHH, Iwasaki, J, Kibble, EAA, Khoo, CA, Scheuplein, NJJ, Seibel, PMM, Lohr, T, Metters, G, Bond, CSS, Norville, IHH, Stubbs, KAA, Harmer, NJJ, Holzgrabe, U, Newton, HJJ, Sarkar-Tyson, M, Zamboni, DS, Debowski, AWW, Bzdyl, NMM, Thomas, DRR, Scott, NEE, Jenkins, CHH, Iwasaki, J, Kibble, EAA, Khoo, CA, Scheuplein, NJJ, Seibel, PMM, Lohr, T, Metters, G, Bond, CSS, Norville, IHH, Stubbs, KAA, Harmer, NJJ, Holzgrabe, U, Newton, HJJ, and Sarkar-Tyson, M

Abstract

Coxiella burnetii is a Gram-negative intracellular pathogen that causes the debilitating disease Q fever, which affects both animals and humans. The only available human vaccine, Q-Vax, is effective but has a high risk of severe adverse reactions, limiting its use as a countermeasure to contain outbreaks. Therefore, it is essential to identify new drug targets to treat this infection. Macrophage infectivity potentiator (Mip) proteins catalyse the folding of proline-containing proteins through their peptidyl prolyl cis-trans isomerase (PPIase) activity and have been shown to play an important role in the virulence of several pathogenic bacteria. To date the role of the Mip protein in C. burnetii pathogenesis has not been investigated. This study demonstrates that CbMip is likely to be an essential protein in C. burnetii. The pipecolic acid derived compounds, SF235 and AN296, which have shown utility in targeting other Mip proteins from pathogenic bacteria, demonstrate inhibitory activities against CbMip. These compounds were found to significantly inhibit intracellular replication of C. burnetii in both HeLa and THP-1 cells. Furthermore, SF235 and AN296 were also found to exhibit antibiotic properties against both the virulent (Phase I) and avirulent (Phase II) forms of C. burnetii Nine Mile Strain in axenic culture. Comparative proteomics, in the presence of AN296, revealed alterations in stress responses with H2O2 sensitivity assays validating that Mip inhibition increases the sensitivity of C. burnetii to oxidative stress. In addition, SF235 and AN296 were effective in vivo and significantly improved the survival of Galleria mellonella infected with C. burnetii. These results suggest that unlike in other bacteria, Mip in C. burnetii is required for replication and that the development of more potent inhibitors against CbMip is warranted and offer potential as novel therapeutics against this pathogen.

Published
2023

38. Symmetrical Derivative of Anthrone as a Novel Receptor for Mercury Ions: Enhanced Performance of Modified Screen-Printed Electrode

Author

Karamjeet Kaur, Susheel K. Mittal, Ashok Kumar SK, Ashwani Kumar, Subodh Kumar, Jonathan P. Metters, and Craig E. Banks

Subjects
modified screen-printed electrode, anthrone derivative, voltammetric sensor for mercury ions, disposable chemical sensor, regeneration of SPE, Organic chemistry, QD241-441
Abstract

Voltammetric sensor using a symmetrical derivative of anthrone3 (1,7-diamino-3,9-dibutyl benzo[1,2,3-de:4,5,6-d’e’]diquinoline-2,8(3H,9H)-dione) (SPE-A) has been developed as a probe for Hg(II) ions. Performance of the probe as screen-printed electrode modified with the receptor (SPE-A) has been compared with anthrone3 in solution phase, using 1:1 water-acetonitrile solvent system. Anthrone3 displayed an electrochemically quasi-reversible nature in voltammograms with both the systems and is presented as a novel disposable voltammetric sensor for mercury ions. Upon interaction with cations, both the electrode systems showed sensitivity towards Hg2+ ions with a lower detection limit of 0.61 µM. The magnitude of the voltammetric current with the SPE-A exhibited three times the current obtained with a bare glassy carbon electrode (GC). Kinetic performance of the SPE-A electrode is better than the GC electrode. The morphological studies indicate reusability of the electrodes.

Published
2021
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39. Change in bathymetry and tidal dynamics after the Bribie Island breakthrough.

Author

Metters, Daryl, Ryan, John, and Daniels, Ralph

Subjects
COASTAL engineering, COASTAL ecology, CLIMATE change, CONSTRUCTION contracts
Abstract

Bribie Island is a barrier island separated from the mainland by Pumicestone Passage. The tidal regime in the northern section is influenced by restrained bathymetric features with diurnal tidal form. The northern end of Bribie Island consists of a narrow sand barrier, and in January 2022, it experienced significant erosion caused by unusually high tides and large waves associated with ex-tropical cyclone Seth. The erosion resulted in a wave wash-over and a tidal breakthrough of the barrier island, forming a new entrance approximately 40 m wide. Changes to bathymetry are assessed via satellite imagery and bathymetric surveys of the passage and breakthrough channel. The breakthrough is orientated in a northwest direction across the island, with a newly formed sand bar extending from the inside of the breakthrough and a tidal delta on the ocean side. Water level data from sites within Pumicestone Passage were analysed to assess changes to the tidal dynamics and tidal levels. The northern section near the breakthrough expressed an increase in the tidal range of 0.46 m with a fall in the mean low water level of -0.21 m and an increase in the mean high-water level of 0.23 metres. The four major tidal constituents increased in amplitude by 0.01 to 0.18 m while the phase changed by between - 22° (O1) and -36° (M2). Southward of the breakthrough, the change in tidal range decreased in a gradient from 0.57 to 0.06 m over the historic tidal range. The tidal form has become more semidiurnal in nature within the passage, changing from strong diurnal to weak diurnal in the northern section. The breakthrough has increased the tidal flow through the northern entrance to Pumicestone Passage and reduced tidal restrictions, hence increasing the tidal range and altering the tidal form. [ABSTRACT FROM AUTHOR]

Published
2023

40. Modelling of Wave-Current interaction along the northern East Coast of Australia.

Author

Faivre, G., Ma, M., Lee, S., Strauss, D., Zhang, H., Tomlinson, R., and Metters, D.

Subjects
THEORY of wave motion, COASTAL zone management, CLIMATE change, METEOROLOGY
Abstract

Protecting coastal infrastructure requires a thorough understanding of coastal processes and wave propagation from deep water. The southeast Queensland coast is exposed to a highly dynamic variety of wave sources including high-energy tropical cyclones, persistent trade winds, east coast lows and Southern Ocean storms. Strong effects of currents on wave propagation often occur near tidal entrances, however the impact of strong currents on wave propagation offshore is rarely considered. The effect of the East Australian Current (EAC) and its variability on deep-water wave propagation to the coast is the focus of this study. We explore wave-current interaction by process-based modelling of the EAC and its influence on wave propagation to coastal waters. Data from a suite of deep water and nearshore monitoring buoys in Southeast Queensland were analysed to study the wave transformation under the influence of the EAC. These data were compared to the Centre for Australian Weather and Climate Research (CAWCR) hindcast wave model data and used for calibration of a local numerical model employed in this study. The results indicate that the wave hindcast model tends to underestimate significant wave height during highenergy events. To address this limitation, an artificial neural network (ANN) model is employed, incorporating output from a hindcast-driven numerical model. The ANN model successfully improves the wave hindcast data used as wave boundaries, thereby enhancing the performance of the local numerical model in accurately representing deep and nearshore wave data. We conducted tests with the coupled wave and hydrodynamic models to compare wave propagation under various scenarios, including tidal forcing, boundary current input from regional models, and local and regional wind conditions. These results demonstrate the variability of the EAC, but also reveal an underestimation of the current compared to observed data. A better understanding of the coupled wave-current interaction can assist future coastal management strategies. [ABSTRACT FROM AUTHOR]

Published
2023

41. Dual phase tsunami modified by shelf resonance on the east coast of Australia.

Author

Metters, Daryl and Waldron, Jim

Subjects
TSUNAMIS, EMERGENCY management, COASTAL engineering, RESONANCE
Abstract

The explosive eruption of the Hunga-Tonga Hunga-Ha'apia volcano transmitted a pressure wave radially from the explosion site, which was reported by pressure sensors across Australia and the globe. Based on modelled traditional seismic tsunami travel speeds, a tsunami was forecast to arrive at the eastern Australia coast within five hours of the eruption. The pressure wave took three hours to reach the east coast of Australia, while the tsunami arrived only 33 minutes after the atmospheric pressure wave. An increase in tsunami amplitude coincides with the modelled arrival time suggesting a two-phase nature of the tsunami. The tsunami resonated over the continental shelf with a peak wave period of 85 to 93 minutes at sites on the central east coast. The peak wave period at an offshore site that has no continental shelf (Norfolk Island) shows a tsunami peak wave period of around 5 minutes. Sea surface perturbations from two tsunami are represented by short period tsunami at an offshore island site, while at coastal east Australia sites, local resonance transferred tsunami energy into longer periods and excited a dominant fundamental oscillation mode through continental shelf resonance. [ABSTRACT FROM AUTHOR]

Published
2023

42. Storm Tide in Moreton Bay - Investigation of Wave Surge Interactions via Experimental Hindcasts.

Author

Smith, Mitchell, Waterhouse, Alexander, Couper, Zachariah, Teakle, Ian, and Metters, Daryl

Subjects
STORM surges, COASTAL zone management, BEACHES, ATMOSPHERIC temperature
Abstract

Existing numerical modelling of storm tide using tide plus surge only approaches within Moreton Bay has underestimated observed peak tidal residuals by over 40%. Scientific debate regarding the source of this "missing" contribution hypothesises it to result from one, or a combination of: storm tide enhancement due to wave breaking and wave-current interaction; limitations of our current wind surface stress parameterisation for surge generation in extreme conditions; and/or the disturbance of existing offshore geostrophic currents by extreme weather events and their 3D interaction with the continental shelf and nearshore bathymetry. This study investigates the wave breaking and wave-current interaction hypothesis by undertaking integrated hydrodynamic and spectral wave modelling hindcast experiments supported by high quality gridded wind, observed water level and wave data at sites throughout Moreton Bay and the Southeast Queensland coast. The case studies for these experiments are the observed regional surge responses occurring during the passages of Ex. Tropical Cyclone Oswald and Tropical Cyclones Dinah, Daisy, Roger, and Oma. For all simulated case study events, the shape and magnitude of modelled residuals resulting from experiments with breaking-wave influences activated provide a 20-30% better match to observations than did experiments with tide plus surge only. Findings also support the theory of offshore geostrophic effects, particularly for remote approach systems TC Roger and TC Oma. Experiments with an allowance for both breaking-wave influences and regional geostrophic mean sea level variations provide a 30 to 95% improvement over experiments with tide plus surge only. The implication of these findings is that each key surge-generating physical process (wind and pressure, waves, and regional offshore ocean weather) requires careful representation in order to reproduce observed storm surges in sub-tropical, semi-open coastal embayments such as Moreton Bay. [ABSTRACT FROM AUTHOR]

Published
2023

48. CT coronary angiography first prior to rapid access chest pain clinic review: a retrospective feasibility study

Author

John Graby, David Murphy, Rhys Metters, Kady Parke, Samantha Jones, Dawn Ellis, Ali Khavandi, Kevin Carson, Rob Lowe, and Jonathan C.L. Rodrigues

Subjects
Radiology, Nuclear Medicine and imaging, General Medicine
Abstract

Objectives: Since rapid access chest pain clinics (RACPC) were established to streamline stable chest pain assessment, CT coronary angiography (CTCA) has become the recommended investigation for patients without known coronary artery disease (CAD), with well-defined indications. This single-centre retrospective study assessed the feasibility of General Practice (GP)-led CTCA prior to RACPC. Methods: RACPC pathway patients without pre-existing CAD electronic records were reviewed (September–October 2019). Feasibility assessments included appropriateness for RACPC, referral clinical data vs RACPC assessment for CTCA indication and safety, and a comparison of actual vs hypothetical pathways, timelines and hospital encounters. Results: 106/172 patients screened met inclusion criteria (mean age 61 ± 14, 51% female). 102 (96%) referrals were ‘appropriate’. No safety concerns were identified to preclude a GP-led CTCA strategy. The hypothetical pathway increased CTCA requests vs RACPC (84 vs 71), whilst improving adherence to guidelines and off-loading other services. 22% (23/106) had no CAD, representing cases where one hospital encounter may be sufficient. The hypothetical pathway would have reduced referral-to-diagnosis by at least a median of 27 days (interquartile range 14–33). Conclusion: A hypothetical GP-led CTCA pathway would have been feasible and safe in a real-world RACPC patient cohort without pre-existing CAD. This novel strategy would have increased referrals for CTCA, whilst streamlining patient pathways and improved NICE guidance adherence. Advances in knowledge: GP-led CTCA is a feasible and safe pathway for patients without pre-existing CAD referred to RACPC, reducing hospital encounters required and may accelerate time to diagnosis. This approach may have implications and opportunities for other healthcare pathways.

Published
2023
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49. Identification of essential genes in Coxiella burnetii

Author

Georgie Metters, Claudia Hemsley, Isobel Norville, and Richard Titball

Subjects
General Medicine
Abstract

Coxiella burnetii is an intracellular pathogen responsible for causing Q fever in humans, a disease with varied presentations ranging from a mild flu-like sickness to a debilitating illness that can result in endocarditis. The intracellular lifestyle of C. burnetii is unique, residing in an acidic phagolysosome-like compartment within host cells. An understanding of the core molecular biology of C. burnetii will greatly increase our understanding of C. burnetii growth, survival and pathogenesis. We used transposon-directed insertion site sequencing (TraDIS) to reveal C. burnetii Nine Mile Phase II genes fundamental for growth and in vitro survival. Screening a transposon library containing >10 000 unique transposon mutants revealed 512 predicted essential genes. Essential routes of synthesis were identified for the mevalonate pathway, as well as peptidoglycan and biotin synthesis. Some essential genes identified (e.g. predicted type IV secretion system effector genes) are typically considered to be associated with C. burnetii virulence, a caveat concerning the axenic media used in the study. Investigation into the conservation of the essential genes identified revealed that 78 % are conserved across all C. burnetii strains sequenced to date, which probably play critical functions. This is the first report of a whole genome transposon screen in C. burnetii that has been undertaken for the identification of essential genes.

Published
2023
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