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Article ; Online: Human leucocytes processed by fast-rate inertial microfluidics retain conventional functional characteristics.

Carvell, Tom / Burgoyne, Paul / Milne, Laura / Campbell, John D M / Fraser, Alasdair R / Bridle, Helen

2024 Volume 21, Issue 212, Page(s) 20230572

Abstract: The manufacturing of clinical cellular therapies is a complex process frequently requiring manipulation of cells, exchange of buffers and volume reduction. Current manufacturing processes rely on either low throughput open centrifugation-based devices, ... ...

Abstract	The manufacturing of clinical cellular therapies is a complex process frequently requiring manipulation of cells, exchange of buffers and volume reduction. Current manufacturing processes rely on either low throughput open centrifugation-based devices, or expensive closed-process alternatives. Inertial focusing (IF) microfluidic devices offer the potential for high-throughput, inexpensive equipment which can be integrated into a closed system, but to date no IF devices have been approved for use in cell therapy manufacturing, and there is limited evidence for the effects that IF processing has on human cells. The IF device described in this study was designed to simultaneously separate leucocytes, perform buffer exchange and provide a volume reduction to the cell suspension, using high flow rates with high Reynolds numbers. The performance and effects of the IF device were characterized using peripheral blood mononuclear cells and isolated monocytes. Post-processing cell effects were investigated using multi-parameter flow cytometry to track cell viability, functional changes and fate. The IF device was highly efficient at separating CD14+ monocytes (approx. 97% to one outlet, approx. 60% buffer exchange, 15 ml min
MeSH term(s)	Humans ; Leukocytes, Mononuclear ; Microfluidics ; Leukocytes ; Cell Survival ; Lab-On-A-Chip Devices
Language	English
Publishing date	2024-03-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2156283-0
ISSN	1742-5662 ; 1742-5689
ISSN (online)	1742-5662
ISSN	1742-5689
DOI	10.1098/rsif.2023.0572
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Article: Lampenflora in a Show Cave in the Great Basin Is Distinct from Communities on Naturally Lit Rock Surfaces in Nearby Wild Caves.

Burgoyne, Jake / Crepeau, Robin / Jensen, Jacob / Smith, Hayden / Baker, Gretchen / Leavitt, Steven D

Microorganisms

2021 Volume 9, Issue 6

Abstract: In show caves, artificial lighting is intended to illuminate striking cave formations for visitors. However, artificial lighting also promotes the growth of novel and diverse biofilm communities, termed lampenflora, that obtain their energy from these ... ...

Abstract	In show caves, artificial lighting is intended to illuminate striking cave formations for visitors. However, artificial lighting also promotes the growth of novel and diverse biofilm communities, termed lampenflora, that obtain their energy from these artificial light sources. Lampenflora, which generally consist of cyanobacteria, algae, diatoms, and bryophytes, discolor formations and introduce novel ecological interactions in cave ecosystems. The source of lampenflora community members and patterns of diversity have generally been understudied mainly due to technological limitations. In this study, we investigate whether members of lampenflora communities in an iconic show cave-Lehman Caves-in Great Basin National Park (GRBA) in the western United States also occur in nearby unlit and rarely visited caves. Using a high-throughput environmental DNA metabarcoding approach targeting three loci-the ITS2 (fungi), a fragment of the 16S (bacteria), and a fragment of 23S (photosynthetic bacteria and eukaryotes)-we characterized diversity of lampenflora communities occurring near artificial light sources in Lehman Caves and rock surfaces near the entrances of seven nearby "wild" caves. Most caves supported diverse and distinct microbial-dominated communities, with little overlap in community members among caves. The lampenflora communities in the show cave were distinct, and generally less diverse, from those occurring in nearby unlit caves. Our results suggest an unidentified source for a significant proportion of lampenflora community members in Lehman Caves, with the majority of community members not found in nearby wild caves. Whether the unique members of the lampenflora communities in Lehman Caves are related to distinct abiotic conditions, increased human visitation, or other factors remains unknown. These results provide a valuable framework for future research exploring lampenflora community assemblies in show caves, in addition to a broad perspective into the range of microbial and lampenflora community members in GRBA. By more fully characterizing these communities, we can better monitor the establishment of lampenflora and design effective strategies for their management and removal.
Language	English
Publishing date	2021-05-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms9061188
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Article ; Online: Long-Distance Avian Migrants Fail to Bring 2.3.4.4b HPAI H5N1 Into Australia for a Second Year in a Row.

Wille, Michelle / Atkinson, Robyn / Barr, Ian G / Burgoyne, Charlotte / Bond, Alexander L / Boyle, David / Christie, Maureen / Dewar, Meagan / Douglas, Tegan / Fitzwater, Teagan / Hassell, Chris / Jessop, Roz / Klaassen, Hiske / Lavers, Jennifer L / Leung, Katherine K-S / Ringma, Jeremy / Sutherland, Duncan R / Klaassen, Marcel

Influenza and other respiratory viruses

2024 Volume 18, Issue 4, Page(s) e13281

MeSH term(s)	Animals ; Humans ; Influenza A Virus, H5N1 Subtype/genetics ; Birds ; Influenza in Birds/epidemiology ; Australia/epidemiology
Language	English
Publishing date	2024-03-30
Publishing country	England
Document type	Letter
ZDB-ID	2274538-5
ISSN	1750-2659 ; 1750-2640
ISSN (online)	1750-2659
ISSN	1750-2640
DOI	10.1111/irv.13281
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Article ; Online: A biomechanical paradigm for axonal insult within the optic nerve head in aging and glaucoma.

Burgoyne, Claude F

Experimental eye research

2010 Volume 93, Issue 2, Page(s) 120–132

Abstract: ... M.R., Pena, J.D., 1997. The optic nerve head in glaucomatous optic neuropathy. Arch Ophthalmol. 115 ... contained herein have been initially presented within or derived from her work (Hernandez, M.R., 2000 ...

Abstract	This article is dedicated to Rosario Hernandez for her warm support of my own work and her genuine enthusiasm for the work of her colleagues throughout her career. I first met Rosario as a research fellow in Harry Quigley's laboratory between 1991 and 1993. Along with Harry, John Morrison, Elaine Johnson, Abe Clark, Colm O'Brien and many others, Rosario's work has provided lamina cribrosa astrocyte cellular mechanisms that are biomechanically plausible and in so doing provided credibility to early notions of the optic nerve head (ONH) as a biomechanical structure. We owe a large intellectual debt to Rosario for her dogged persistence in the characterization of the ONH astrocyte and lamina cribrosacyte in age and disease. Two questions run through her work and remain of central importance today. First, how do astrocytes respond to and alter the biomechanical environment of the ONH and the physiologic stresses created therein? Second, how do these physiologic demands on the astrocyte influence their ability to deliver the support to retinal ganglion cell axon transport and flow against the translaminar pressure gradient? The purpose of this article is to summarize what is known about the biomechanical determinants of retinal ganglion cell axon physiology within the ONH in the optic neuropathy of aging and Glaucoma. My goal is to provide a biomechanical framework for this discussion. This framework assumes that the ONH astrocytes and glia fundamentally support and influence both the lamina cribrosa extracellular matrix and retinal ganglion cell axon physiology. Rosario Hernandez was one of the first investigators to recognize the implications of this unique circumstance. Many of the ideas contained herein have been initially presented within or derived from her work (Hernandez, M.R., 2000. The optic nerve head in glaucoma: role of astrocytes in tissue remodeling. Prog Retin Eye Res. 19, 297-321.; Hernandez, M.R., Pena, J.D., 1997. The optic nerve head in glaucomatous optic neuropathy. Arch Ophthalmol. 115, 389-395.).
MeSH term(s)	Aging/physiology ; Astrocytes/physiology ; Axonal Transport/physiology ; Axons/physiology ; Glaucoma/physiopathology ; Humans ; Optic Disk/physiopathology ; Optic Nerve Diseases/physiopathology ; Retinal Ganglion Cells/physiology
Language	English
Publishing date	2010-09-16
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80122-7
ISSN	1096-0007 ; 0014-4835
ISSN (online)	1096-0007
ISSN	0014-4835
DOI	10.1016/j.exer.2010.09.005
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Article ; Online: Cabozantinib plus atezolizumab in previously untreated advanced hepatocellular carcinoma and previously treated gastric cancer and gastroesophageal junction adenocarcinoma: results from two expansion cohorts of a multicentre, open-label, phase 1b trial (COSMIC-021).

Li, Daneng / Loriot, Yohann / Burgoyne, Adam M / Cleary, James M / Santoro, Armando / Lin, Daniel / Aix, Santiago Ponce / Garrido-Laguna, Ignacio / Sudhagoni, Ramu / Guo, Xiang / Andrianova, Svetlana / Paulson, Scott

EClinicalMedicine

2023 Volume 67, Page(s) 102376

Abstract: Background: Cabozantinib is approved for previously treated advanced hepatocellular carcinoma (aHCC) and has been investigated in gastric cancer (GC) and gastroesophageal junction adenocarcinoma (GEJ). Atezolizumab plus bevacizumab is approved for ... ...

Abstract	Background: Cabozantinib is approved for previously treated advanced hepatocellular carcinoma (aHCC) and has been investigated in gastric cancer (GC) and gastroesophageal junction adenocarcinoma (GEJ). Atezolizumab plus bevacizumab is approved for unresectable or metastatic HCC untreated with prior systemic therapy. We evaluated efficacy and safety of cabozantinib plus atezolizumab in aHCC previously untreated with systemic anticancer therapy or previously treated GC/GEJ. Methods: COSMIC-021 (ClinicalTrials.gov, NCT03170960) is an open-label, phase 1b study in solid tumours with a dose-escalation stage followed by tumour-specific expansion cohorts, including aHCC (cohort 14) and GC/GEJ (cohort 15). Eligible patients were aged ≥18 years with measurable locally advanced, metastatic, or recurrent disease per RECIST version 1.1. Patients received oral cabozantinib 40 mg daily and intravenous atezolizumab 1200 mg once every 3 weeks until progressive disease or unacceptable toxicity. The primary endpoint was investigator-assessed objective response rate per RECIST version 1.1. Findings: Patients were screened between February 14, 2019, and May 7, 2020, and 61 (30 aHCC, 31 GC/GEJ) were enrolled and received at least one dose of study treatment. Median duration of follow-up was 31.2 months (IQR 28.5-32.7) for aHCC and 30.4 months (28.7-31.9) for GC/GEJ. Objective response rate was 13% (4/30, 95% CI 4-31) for aHCC and 0% (95% CI 0-11) for GC/GEJ. Six (20%) aHCC patients and three (10%) GC/GEJ patients had treatment-related adverse events resulting in discontinuation of either study drug. Interpretation: Cabozantinib plus atezolizumab had clinical activity with a manageable safety profile in aHCC previously untreated with systemic anticancer therapy. Clinical activity of cabozantinib plus atezolizumab was minimal in previously treated GC/GEJ. Funding: Exelixis, Inc., Alameda, CA, USA.
Language	English
Publishing date	2023-12-21
Publishing country	England
Document type	Journal Article
ISSN	2589-5370
ISSN (online)	2589-5370
DOI	10.1016/j.eclinm.2023.102376
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Article ; Online: Personalising monitoring for chemotherapy patients through predicting deterioration in renal and hepatic function.

Chambers, Pinkie / Watson, Matthew / Bridgewater, John / Forster, Martin D / Roylance, Rebecca / Burgoyne, Rebecca / Masento, Sebastian / Steventon, Luke / Harmsworth King, James / Duncan, Nick / Al Moubayed, Noura

Cancer medicine

2023 Volume 12, Issue 17, Page(s) 17856–17865

Abstract: Background: In those receiving chemotherapy, renal and hepatic dysfunction can increase the risk of toxicity and should therefore be monitored. We aimed to develop a machine learning model to identify those patients that need closer monitoring, enabling ...

Abstract	Background: In those receiving chemotherapy, renal and hepatic dysfunction can increase the risk of toxicity and should therefore be monitored. We aimed to develop a machine learning model to identify those patients that need closer monitoring, enabling a safer and more efficient service. Methods: We used retrospective data from a large academic hospital, for patients treated with chemotherapy for breast cancer, colorectal cancer and diffuse-large B-cell lymphoma, to train and validate a Multi-Layer Perceptrons (MLP) model to predict the outcomes of unacceptable rises in bilirubin or creatinine. To assess the performance of the model, validation was performed using patient data from a separate, independent hospital using the same variables. Using this dataset, we evaluated the sensitivity and specificity of the model. Results: 1214 patients in total were identified. The training set had almost perfect sensitivity and specificity of >0.95; the area under the curve (AUC) was 0.99 (95% CI 0.98-1.00) for creatinine and 0.97 (95% CI: 0.95-0.99) for bilirubin. The validation set had good sensitivity (creatinine: 0.60, 95% CI: 0.55-0.64, bilirubin: 0.54, 95% CI: 0.52-0.56), and specificity (creatinine 0.98, 95% CI: 0.96-0.99, bilirubin 0.90, 95% CI: 0.87-0.94) and area under the curve (creatinine: 0.76, 95% CI: 0.70, 0.82, bilirubin 0.72, 95% CI: 0.68-0.76). Conclusions: We have demonstrated that a MLP model can be used to reduce the number of blood tests required for some patients at low risk of organ dysfunction, whilst improving safety for others at high risk.
MeSH term(s)	Humans ; Retrospective Studies ; Creatinine ; Machine Learning ; Sensitivity and Specificity ; Bilirubin
Chemical Substances	Creatinine (AYI8EX34EU) ; Bilirubin (RFM9X3LJ49)
Language	English
Publishing date	2023-08-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2659751-2
ISSN	2045-7634 ; 2045-7634
ISSN (online)	2045-7634
ISSN	2045-7634
DOI	10.1002/cam4.6418
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Article: Targeting the chromaffin cell.

Burgoyne, R D

Trends in cell biology

2004 Volume 5, Issue 12, Page(s) 471–473

Language	English
Publishing date	2004-03-01
Publishing country	England
Document type	Journal Article
ZDB-ID	30122-x
ISSN	1879-3088 ; 0962-8924
ISSN (online)	1879-3088
ISSN	0962-8924
DOI	10.1016/s0962-8924(00)89117-5
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Zs.A 3410: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)

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Article: The Challenge of Variable Costs in Decisions Based on Cost-Effectiveness Evidence: A Case Study for Brodalumab.

Brixner, Diana / Oderda, Gary / Biskupiak, Joseph / Burgoyne, Douglas S / Avey, Steven G / Feldman, Steven R

American health & drug benefits

2019 Volume 12, Issue 1, Page(s) 22–26

Abstract: Background: Payers often consider cost-effectiveness studies for new drugs when making decisions on coverage, formulary position, and budgets; however, cost-effectiveness studies are often calculated using estimated pricing before a drug's launch. If ... ...

Abstract	Background: Payers often consider cost-effectiveness studies for new drugs when making decisions on coverage, formulary position, and budgets; however, cost-effectiveness studies are often calculated using estimated pricing before a drug's launch. If the drug's price changes on or after launch, or if rebate programs are initiated, cost-effectiveness studies need to be updated to prevent payers from making decisions using inaccurate value assumptions, which can lead to unexpected financial impacts and potentially delay patient access to drugs. Objective: To evaluate how lower at-launch drug pricing versus initial estimated pricing affects cost-effectiveness ratios and potentially influences treatment decisions, using the case study of brodalumab, a biologic drug indicated for the treatment of moderate-to-severe plaque psoriasis. Methods: We compared the estimated cost-effectiveness of brodalumab, which was published in a December 2016 Institute for Clinical and Economic Review (ICER) report based on estimated pricing, with the drug's cost-effectiveness based on its actual pricing after its approval. Discussion: The 2016 ICER report on the cost-effectiveness of targeted immunomodulators indicated for the treatment of moderate-to-severe plaque psoriasis, brodalumab's price was estimated to be $4267 by averaging the cost of its likely competitors. Brodalumab's effectiveness as a treatment for moderate-to-severe plaque psoriasis is high in clinical trials, but its estimated cost placed it as the fourth most cost-effective targeted immunomodulatory drug in the ICER report. On its approval in February 2017, brodalumab's newly estimated base price was $3900, based on its prelaunch price. Calculations using this base price placed brodalumab as the most cost-effective option among targeted immunomodulators in this setting. At the time this current article was written, brodalumab's cost was $3500, making it even more cost-effective. Conclusion: Because payers, providers, and patients are all concerned with achieving better outcomes for the often painful and disfiguring disease of plaque psoriasis, while controlling costs, updating cost-effectiveness data when new pricing information becomes available may reveal significant cost differences to help stakeholders make better decisions about their population's healthcare outcomes and costs.
Language	English
Publishing date	2019-03-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2853721-X
ISSN	1942-2970 ; 1942-2962
ISSN (online)	1942-2970
ISSN	1942-2962
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Article ; Online: Venomous gland transcriptome and venom proteomic analysis of the scorpion Androctonus amoreuxi reveal new peptides with anti-SARS-CoV-2 activity.

Ghazal, Ahmad / Clarke, David / Abdel-Rahman, Mohamed A / Ribeiro, Antonio / Collie-Duguid, Elaina / Pattinson, Craig / Burgoyne, Kate / Muhammad, Taj / Alfadhel, Sanad / Heidari, Zeynab / Samir, Reham / Gerges, Mariam M / Nkene, Istifanus / Colamarino, Rosa A / Hijazi, Karolin / Houssen, Wael E

Peptides

2023 Volume 173, Page(s) 171139

Abstract: The recent COVID-19 pandemic shows the critical need for novel broad spectrum antiviral agents. Scorpion venoms are known to contain highly bioactive peptides, several of which have demonstrated strong antiviral activity against a range of viruses. We ... ...

Abstract	The recent COVID-19 pandemic shows the critical need for novel broad spectrum antiviral agents. Scorpion venoms are known to contain highly bioactive peptides, several of which have demonstrated strong antiviral activity against a range of viruses. We have generated the first annotated reference transcriptome for the Androctonus amoreuxi venom gland and used high performance liquid chromatography, transcriptome mining, circular dichroism and mass spectrometric analysis to purify and characterize twelve previously undescribed venom peptides. Selected peptides were tested for binding to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and inhibition of the spike RBD - human angiotensin-converting enzyme 2 (hACE2) interaction using surface plasmon resonance-based assays. Seven peptides showed dose-dependent inhibitory effects, albeit with IC
MeSH term(s)	Animals ; Humans ; SARS-CoV-2/metabolism ; Scorpions/chemistry ; COVID-19 ; Transcriptome ; Proteomics ; Pandemics ; Peptides/metabolism ; Antiviral Agents/pharmacology ; Scorpion Venoms/chemistry ; Protein Binding ; Animals, Poisonous ; Spike Glycoprotein, Coronavirus
Chemical Substances	spike protein, SARS-CoV-2 ; Peptides ; Antiviral Agents ; Scorpion Venoms ; Spike Glycoprotein, Coronavirus
Language	English
Publishing date	2023-12-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	769028-9
ISSN	1873-5169 ; 0196-9781
ISSN (online)	1873-5169
ISSN	0196-9781
DOI	10.1016/j.peptides.2023.171139
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Article ; Online: Detection of

Burgoyne, Edward D / Molina-Osorio, Andrés F / Moshrefi, Reza / Shanahan, Rachel / McGlacken, Gerard P / Stockmann, Talia Jane / Scanlon, Micheál D

The Analyst

2020 Volume 145, Issue 21, Page(s) 7000–7008

Abstract: Miniaturization of electrochemical detection methods for point-of-care-devices is ideal for their integration and use within healthcare environments. Simultaneously, the prolific pathogenic bacteria Pseudomonas aeruginosa poses a serious health risk to ... ...

Abstract	Miniaturization of electrochemical detection methods for point-of-care-devices is ideal for their integration and use within healthcare environments. Simultaneously, the prolific pathogenic bacteria Pseudomonas aeruginosa poses a serious health risk to patients with compromised immune systems. Recognizing these two factors, a proof-of-concept electrochemical method employing a micro-interface between water and oil (w/o) held at the tip of a pulled borosilicate glass capillary is presented. This method targets small molecules produced by P. aeruginosa colonies as signalling factors that control colony growth in a pseudo-multicellular process known as quorum sensing (QS). The QS molecules of interest are 4-hydroxy-2-heptylquinoline (HHQ) and 2-heptyl-3,4-dihydroxyquinoline (PQS, Pseudomonas quinolone signal). Hydrophobic HHQ and PQS molecules, dissolved in the oil phase, were observed electrochemically to facilitate proton transfer across the w/o interface. This interfacial complexation can be exploited as a facile electrochemical detection method for P. aeruginosa and is advantageous as it does not depend on the redox activity of HHQ/PQS. Interestingly, the limit-of-linearity is reached as [H+] ≈ [ligand]. Density functional theory calculations were performed to determine the proton affinities and gas-phase basicities of HHQ/PQS, as well as elucidate the likely site of stepwise protonation within each molecule.
MeSH term(s)	Humans ; Protons ; Pseudomonas aeruginosa ; Quorum Sensing ; Signal Transduction
Chemical Substances	Protons
Language	English
Publishing date	2020-09-01
Publishing country	England
Document type	Journal Article
ZDB-ID	210747-8
ISSN	1364-5528 ; 0003-2654
ISSN (online)	1364-5528
ISSN	0003-2654
DOI	10.1039/d0an01245a
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