Publications by authors named "John Betts"

9 Publications

  • Page 1 of 1

Design and development of a new ambr250® bioreactor vessel for improved cell and gene therapy applications.

Biotechnol Lett 2021 May 2;43(5):1103-1116. Epub 2021 Feb 2.

Advanced Centre for Biochemical Engineering, Department of Biochemical Engineering, University College London, Gower Street, London, WC1E 6BT, UK.

The emergence of cell and gene therapies has generated significant interest in their clinical and commercial potential. However, these therapies are prohibitively expensive to manufacture and can require extensive time for development due to our limited process knowledge and understanding. The automated ambr250® stirred-tank bioreactor platform provides an effective platform for high-throughput process development. However, the original dual pitched-blade 20 mm impeller and baffles proved sub-optimal for cell therapy candidates that require suspension of microcarriers (e.g. for the culture of adherent human mesenchymal stem cells) or other particles such as activating Dynabeads® (e.g. for the culture of human T-cells). We demonstrate the development of a new ambr250® stirred-tank bioreactor vessel which has been designed specifically to improve the suspension of microcarriers/beads and thereby improve the culture of such cellular systems. The new design is unbaffled and has a single, larger elephant ear impeller. We undertook a range of engineering and physical characterizations to determine which vessel and impeller configuration would be most suitable for suspension based on the minimum agitation speed (N) and associated specific power input (P/V). A vessel (diameter, T, = 60 mm) without baffles and incorporating a single elephant ear impeller (diameter 30 mm and 45° pitch-blade angle) was selected as it had the lowest (P/V) and therefore potentially, based on Kolmogorov concepts, was the most flexible system. These experimentally-based conclusions were further validated firstly with computational fluid dynamic (CFD) simulations and secondly experimental studies involving the culture of both T-cells with Dynabeads® and hMSCs on microcarriers. The new ambr250® stirred-tank bioreactor successfully supported the culture of both cell types, with the T-cell culture demonstrating significant improvements compared to the original ambr250® and the hMSC-microcarrier culture gave significantly higher yields compared with spinner flask cultures. The new ambr250® bioreactor vessel design is an effective process development tool for cell and gene therapy candidates and potentially for autologous manufacture too.
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http://dx.doi.org/10.1007/s10529-021-03076-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043889PMC
May 2021

Molecular profiling of Peru Balsam reveals active ingredients responsible for its pharmaceutical properties.

Nat Prod Res 2020 Apr 21:1-6. Epub 2020 Apr 21.

Research Laboratory for Archaeology and the History of Art, University of Oxford, Oxford, UK.

Peru Balsam, a resinous substance derived from var. , has historically been used as a topical ointment for various skin conditions such as scabies, poorly healing wounds, eczema, and haemorrhoids. The ingredients responsible for these properties are not fully elucidated. We investigated the chemical composition of two Peru Balsam samples, one historical and one modern, using gas chromatography/mass spectrometry to identify the active ingredients responsible for its pharmaceutical properties. Both Peru Balsam specimens investigated had similar compositions, showing the stability of the substance. Components identified are effective against scabies, exhibit antimicrobial activity and aid skin penetration. These properties are consistent with historical uses of Peru Balsam. Several ingredients are also known allergens. This study, combining chemical information with scientific literature related to pharmaceutical properties of natural substances, represents a breakthrough in the elucidation of active ingredients in Peru Balsam.
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http://dx.doi.org/10.1080/14786419.2020.1753056DOI Listing
April 2020

The effects of local socio-political events on group cohesion in online far-right communities.

PLoS One 2020 30;15(3):e0230302. Epub 2020 Mar 30.

Department of Criminology, University of Derby, Derby, United Kingdom.

In recent years, the reach and influence of far-right ideologies have been extended through online communities with devastating effects in the real world. In this research, we examine how far-right online communities can be empowered by socio-political events that are significant to them. Using over 14 years of data extracted from an Australian national sub-forum of a global online white supremacist community, we investigate whether the group cohesion of the community is affected by local race riots. Our analysis shows that the online community, not only became more cohesive after the riots, but was also reinvigorated by highly active new members who joined during the week of the riots or soon after. These changes were maintained over the longer-term, highlighting pervasive ramifications of the local socio-political context for this white supremacist community. Pre-registered analyses of data extracted from other white supremacist online communities (in South Africa and the United Kingdom) show similar effects on some of the indicators of group cohesion, but of reduced magnitude, and not as enduring as the effects found in the context of the Australian far-right online community.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0230302PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105128PMC
June 2020

Leadless Permanent Pacing: A Single Centre Australian Experience.

Heart Lung Circ 2019 Nov 15;28(11):1677-1682. Epub 2018 Oct 15.

Department of Cardiology, The Prince Charles Hospital, Brisbane, Qld, Australia; Faculty of Medicine, University of Queensland, Brisbane, Qld, Australia.

Background: To describe the performance and clinical outcomes of consecutive patients having a leadless pacemaker (LP) implanted at a single institution.

Methods: Clinical data and device parameters were prospectively collected on all patients undergoing LP implantation from November 2015 to April 2018.

Results: A total of 79 patients (52 male), median age of 78 years, was included. Leadless pacemaker implantation was successful in 76 patients (96%). Implantation failed in two patients due to excessive venous tortuosity and due to inadequate sensing in another. Seventy-three (73) patients (96%) had chronic atrial fibrillation and all had a Class I or II indication for pacing. Procedure time was 29minutes (IQR 21-43) and fluoroscopy time was 8minutes (IQR 5-13). The median R wave at implant was 11.2mV (IQR 6.9-15.0). The median capture threshold at 0.24ms was 0.5V (IQR 0.4-0.9) and impedance was 754Ω (IQR 680-880). Intraprocedural acute dislodgement occurred in one patient following cutting of the tether but successful snaring and reimplantation was performed. During a median follow-up of 355days (range 9-905), overall electrical performance has been excellent. No patients have been readmitted for device revision or complications. Five (5) patients (7%) died during follow-up from unrelated causes.

Conclusions: Leadless pacemakers can be implanted safely and effectively in the majority of patients. Device electrical performance was excellent over a median follow-up of 12 months.
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http://dx.doi.org/10.1016/j.hlc.2018.09.014DOI Listing
November 2019

High throughput automated microbial bioreactor system used for clone selection and rapid scale-down process optimization.

Biotechnol Prog 2018 01 10;34(1):58-68. Epub 2017 Aug 10.

The Advanced Centre for Biochemical Engineering, Department of Biochemical Engineering, University College London, Gower Street, Bernard Katz Building, London, WC1E 6BT, U.K.

High throughput automated fermentation systems have become a useful tool in early bioprocess development. In this study, we investigated a 24 x 15 mL single use microbioreactor system, ambr 15f, designed for microbial culture. We compared the fed-batch growth and production capabilities of this system for two Escherichia coli strains, BL21 (DE3) and MC4100, and two industrially relevant molecules, hGH and scFv. In addition, different carbon sources were tested using bolus, linear or exponential feeding strategies, showing the capacity of the ambr 15f system to handle automated feeding. We used power per unit volume (P/V) as a scale criterion to compare the ambr 15f with 1 L stirred bioreactors which were previously scaled-up to 20 L with a different biological system, thus showing a potential 1,300 fold scale comparability in terms of both growth and product yield. By exposing the cells grown in the ambr 15f system to a level of shear expected in an industrial centrifuge, we determined that the cells are as robust as those from a bench scale bioreactor. These results provide evidence that the ambr 15f system is an efficient high throughput microbial system that can be used for strain and molecule selection as well as rapid scale-up. © 2017 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers Biotechnol. Prog., 34:58-68, 2018.
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http://dx.doi.org/10.1002/btpr.2534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836883PMC
January 2018

Ultra-low radiation dose during electrophysiology procedures using optimized new generation fluoroscopy technology.

Pacing Clin Electrophysiol 2017 Aug 21;40(8):947-954. Epub 2017 Jul 21.

Cardiology Department, The Prince Charles Hospital, Chermside, Queensland, Australia.

Background: Electrophysiology procedures require fluoroscopic guidance, with the associated potentially adverse effects of ionizing radiation. Newer fluoroscopy systems have more features that enable dose-reduction strategies. This study aimed to investigate any reduction in radiation dose between an older fluoroscopy system (Philips Integris H5000, Philips Healthcare, Einhoven, Netherlands) and one of the latest systems (Siemens Artis Q, Siemens Healthcare, Erlangen, Germany), optimized with dose-reduction strategies.

Methods: Radiation dose measures were collected over a 2-year period in a single electrophysiology laboratory. Procedures were separated into seven groups: devices, biventricular devices, electrophysiology studies, standard radiofrequency ablation, complex atrial ablation, ablation for ventricular arrhythmias, and pulmonary vein isolation. In the first year, an older fluoroscopy system was used, and in the second year, a new system, with dose reduction strategies. Comparisons were also made to the literature with regard to radiation dose levels.

Results: Patient characteristics, fluoroscopy times, number of digital acquisitions, procedural times, and procedural success were largely similar between the old and new system across procedure groups. Overall dose area product (DAP) was reduced by 91% (5.0 [2.0-17.0] to 0.45 [0.16-2.61] Gycm [P > 0.001]) with the new system and was lower across all groups. DAP readings with the new system are some of the lowest published in the literature in all groups.

Conclusion: An optimized contemporary digital fluoroscopy system, with low radiation dose configuration and continued good procedural practice, can result in ultra-low radiation levels for all electrophysiology procedures, without compromising procedural time or procedural success.
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http://dx.doi.org/10.1111/pace.13141DOI Listing
August 2017

Nanophyetus salmincola, vector of the salmon poisoning disease agent Neorickettsia helminthoeca, harbors a second pathogenic Neorickettsia species.

Vet Parasitol 2016 Oct 4;229:107-109. Epub 2016 Oct 4.

Department of Biology, University of North Dakota, Grand Forks, ND, 10 Cornell Street, 58202, USA. Electronic address:

The trematode Nanophyetus salmincola is known as the carrier of Neorickettsia helminthoeca, an obligate intracellular endosymbiotic bacterium that causes salmon poisoning disease (SPD), a fatal disease of dogs. The bacteria are maintained through the complex life cycle of N. salmincola that involves snails Juga plicifera as the first intermediate host, salmonid fishes as the second intermediate host and fish-eating mammals as definitive hosts. N. salmincola was also found to harbor a second species of Neorickettsia that causes the Elokomin fluke fever disease (EFF) which has clinical signs similar to SPD in bears, but only low grade illness in dogs. The EFF agent has not been sequenced. In this study we identified N. salmincola as the vector of yet additional species of Neorickettsia known as Stellanchasmus falcatu (SF) agent using DNA sequencing.
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http://dx.doi.org/10.1016/j.vetpar.2016.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5123816PMC
October 2016

A radiobiology-based inverse treatment planning method for optimisation of permanent l-125 prostate implants in focal brachytherapy.

Phys Med Biol 2016 Jan 16;61(1):430-44. Epub 2015 Dec 16.

Department Physical Sciences Peter MacCallum Cancer Centre, Vic, 3002, Australia. Sir Peter MacCallum Department of Oncology, University of Melbourne, Vic, 3010, Australia.

Treatment plans for ten patients, initially treated with a conventional approach to low dose-rate brachytherapy (LDR, 145 Gy to entire prostate), were compared with plans for the same patients created with an inverse-optimisation planning process utilising a biologically-based objective. The 'biological optimisation' considered a non-uniform distribution of tumour cell density through the prostate based on known and expected locations of the tumour. Using dose planning-objectives derived from our previous biological-model validation study, the volume of the urethra receiving 125% of the conventional prescription (145 Gy) was reduced from a median value of 64% to less than 8% whilst maintaining high values of TCP. On average, the number of planned seeds was reduced from 85 to less than 75. The robustness of plans to random seed displacements needs to be carefully considered when using contemporary seed placement techniques. We conclude that an inverse planning approach to LDR treatments, based on a biological objective, has the potential to maintain high rates of tumour control whilst minimising dose to healthy tissue. In future, the radiobiological model will be informed using multi-parametric MRI to provide a personalised medicine approach.
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http://dx.doi.org/10.1088/0031-9155/61/1/430DOI Listing
January 2016

Monitoring moving queries inside a safe region.

ScientificWorldJournal 2014 16;2014:630396. Epub 2014 Feb 16.

Clayton School of Information Technology, Monash University, Clayton, VIC 3800, Australia.

With mobile moving range queries, there is a need to recalculate the relevant surrounding objects of interest whenever the query moves. Therefore, monitoring the moving query is very costly. The safe region is one method that has been proposed to minimise the communication and computation cost of continuously monitoring a moving range query. Inside the safe region the set of objects of interest to the query do not change; thus there is no need to update the query while it is inside its safe region. However, when the query leaves its safe region the mobile device has to reevaluate the query, necessitating communication with the server. Knowing when and where the mobile device will leave a safe region is widely known as a difficult problem. To solve this problem, we propose a novel method to monitor the position of the query over time using a linear function based on the direction of the query obtained by periodic monitoring of its position. Periodic monitoring ensures that the query is aware of its location all the time. This method reduces the costs associated with communications in client-server architecture. Computational results show that our method is successful in handling moving query patterns.
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http://dx.doi.org/10.1155/2014/630396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3947889PMC
January 2015