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1. Analysis of Osteosarcoma Cell Lines and Patient Tissue Using a 3D In Vivo Tumor Model—Possible Effects of Punicalagin

Author

Anna Rebecca Dorn, Sara Neff, Sophia Hupp, Melissa Engelhardt, Eric Pion, Ulrich Lenze, Carolin Knebel, Anna Duprée, Simone Schewe, Markus Weber, Christian Wulbrand, Axel Hillmann, Florian Weber, Phillip Clarke, Philipp Kainz, Thiha Aung, and Silke Haerteis

Subjects
osteosarcoma, CAM assay, 3D in vivo tumor model, punicalagin, MTT assay, angiogenesis, Cytology, QH573-671
Abstract

Osteosarcomas are the most common primary malignant bone tumors and mostly affect children, adolescents, and young adults. Despite current treatment options such as surgery and polychemotherapy, the survival of patients with metastatic disease remains poor. In recent studies, punicalagin has reduced the cell viability, angiogenesis, and invasion in cell culture trials. The aim of this study was to examine the effects of punicalagin on osteosarcomas in a 3D in vivo tumor model. Human osteosarcoma biopsies and SaOs-2 and MG-63 cells, were grown in a 3D in vivo chorioallantoic membrane (CAM) model. After a cultivation period of up to 72 h, the tumors received daily treatment with punicalagin for 4 days. Weight measurements of the CAM tumors were performed, and laser speckle contrast imaging (LSCI) and a deep learning-based image analysis software (CAM Assay Application v.3.1.0) were used to measure angiogenesis. HE, Ki-67, and Caspase-3 staining was performed after explantation. The osteosarcoma cell lines SaOs-2 and MG-63 and osteosarcoma patient tissue displayed satisfactory growth patterns on the CAM. Treatment with punicalagin decreased tumor weight, proliferation, and tumor-induced angiogenesis, and the tumor tissue showed pro-apoptotic characteristics. These results provide a robust foundation for the implementation of further studies and show that punicalagin offers a promising supplementary treatment option for osteosarcoma patients. The 3D in vivo tumor model represents a beneficial model for the testing of anti-cancer therapies.

Published
2024
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2. Feasibility and acceptability of the use of flash glucose monitoring encountered by Indigenous Australians with type 2 diabetes mellitus: initial experiences from a pilot study

Author

Audrey Sing Yi Eer, Rebecca Chia Yee Ho, Tracey Hearn, Mariam Hachem, Megan Freund, Luke James Burchill, Sharon Atkinson-Briggs, Satpal Singh, Sandra Eades, Richard Charles O’Brien, John Stuart Furler, David Norman O’Neal, David Andrew Story, Jeffrey David Zajac, Sabine Braat, Alex Brown, Phillip Clarke, Ashim Kumar Sinha, Anna Gerardina McLean, Stephen Morris Twigg, and Elif Ilhan Ekinci

Subjects
Indigenous Australian, Aboriginal people, Type 2 diabetes mellitus, Flash glucose monitoring, Qualitative research, Phenomenological study, Public aspects of medicine, RA1-1270
Abstract

Abstract Background Type 2 diabetes mellitus (T2DM) is highly prevalent within the Indigenous Australian community. Novel glucose monitoring technology offers an accurate approach to glycaemic management, providing real-time information on glucose levels and trends. The acceptability and feasibilility of this technology in Indigenous Australians with T2DM has not been investigated. Objective This feasibility phenomenological study aims to understand the experiences of Indigenous Australians with T2DM using flash glucose monitoring (FGM). Methods Indigenous Australians with T2DM receiving injectable therapy (n = 8) who used FGM (Abbott Freestyle Libre) for 6-months, as part of a clinical trial, participated in semi-structured interviews. Thematic analysis of the interviews was performed using NVivo12 Plus qualitative data analysis software (QSR International). Results Six major themes emerged: 1) FGM was highly acceptable to the individual; 2) FGM’s convenience was its biggest benefit; 3) data from FGM was a tool to modify lifestyle choices; 4) FGM needed to be complemented with health professional support; 5) FGM can be a tool to engage communities in diabetes management; and 6) cost of the device is a barrier to future use. Conclusions Indigenous Australians with T2DM had positive experiences with FGM. This study highlights future steps to ensure likelihood of FGM is acceptable and effective within the wider Indigenous Australian community.

Published
2023
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3. Patient and clinician characteristics and preferences for increasing participation in placebo surgery trials: a scoping review of attributes to inform a discrete choice experiment

Author

Madeleine Hinwood, Laura Wall, Danielle Lang, Zsolt J. Balogh, Angela Smith, Michelle Dowsey, Phillip Clarke, Peter Choong, Samantha Bunzli, and Francesco Paolucci

Subjects
Medicine (General), R5-920
Abstract

Abstract Background Orthopaedic surgeries include some of the highest volume surgical interventions globally; however, studies have shown that a significant proportion of patients report no clinically meaningful improvement in pain or function after certain procedures. As a result, there is increasing interest in conducting randomised placebo-controlled trials in orthopaedic surgery. However, these frequently fail to reach recruitment targets suggesting a need to improve trial design to encourage participation. The objective of this study was to systematically scope the available evidence on patient and clinician values and preferences which may influence the decision to participate in placebo surgery trial. Methods A systematic review was conducted via a literature search in the MEDLINE, Embase, PsycInfo, CINAHL, and EconLit databases as of 19 July 2021, for studies of any design (except commentaries or opinion pieces) based on two key concepts: patient and clinician characteristics, values and preferences, and placebo surgery trials. Results Of 3424 initial articles, we retained 18 eligible studies. Characteristics, preferences, values, and attitudes of patients (including levels of pain/function, risk/benefit perception, and altruism) and of clinicians (including concerns regarding patient deception associated with placebo, and experience/training in research) influenced their decisions to participate in placebo-controlled trials. Furthermore, some aspects of trial design, including randomisation procedures, availability of the procedure outside of the trial, and the information and consent procedures used, also influenced decisions to participate. Conclusion Participant recruitment is a significant challenge in placebo surgery trials, and individual decisions to participate appear to be sensitive to preferences around treatment. Understanding and quantifying the role patient and clinician preferences may play in surgical trials may contribute to the optimisation of the design and implementation of clinical trials in surgery.

Published
2022
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4. Promoting Independence Through quality dementia Care at Home (PITCH): a research protocol for a stepped-wedge cluster-randomised controlled trial

Author

Steven Savvas, Anita M. Y. Goh, Frances Batchelor, Colleen Doyle, Erica Wise, Esther Tan, Anita Panayiotou, Sue Malta, Margaret Winbolt, Phillip Clarke, Jason Burton, Lee-Fay Low, Samantha M. Loi, Anne Fairhall, Meg Polacsek, Jay Stiles, Fenny Muliadi, Nadia Chau, Samuel Scherer, David Ames, Tanara Vieira Sousa, and Briony Dow

Subjects
Home care, Aged care, Dementia, Home care worker, HCW, Aged care staff, Medicine (General), R5-920
Abstract

Abstract Background Home care service providers are increasingly supporting clients living with dementia. Targeted and comprehensive dementia-specific training for home care staff is necessary to meet this need. This study evaluates a training programme delivered to care staff (paid personal carers) of clients living with dementia at home. Methods This study is a pragmatic stepped-wedge cluster-randomised controlled trial (SW-CRT). Home care workers (HCWs) from seven home care service providers are grouped into 18 geographical clusters. Clusters are randomly assigned to intervention or control groups. The intervention group receives 7 h of a dementia education and upskilling programme (Promoting Independence Through quality dementia Care at Home [PITCH]) after baseline measures. The control group receives PITCH training 6 months after baseline measures. This approach will ensure that all participants are offered the program. Home care clients living with dementia are also invited to participate, as well as their family carers. The primary outcome measure is HCWs’ sense of competence in dementia care provision. Discussion Upskilling home care staff is needed to support the increasing numbers of people living with dementia who choose to remain at home. This study uses a stepped-wedge cluster-randomised trial to evaluate a training programme (PITCH) for dementia care that is delivered to front-line HCWs. Trial registration anzctr.org.au ; ACTRN12619000251123. Registered on 20 February 2019.

Published
2021
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5. The impact of viral mutations on recognition by SARS-CoV-2 specific T cells

Author

Thushan I. de Silva, Guihai Liu, Benjamin B. Lindsey, Danning Dong, Shona C. Moore, Nienyun Sharon Hsu, Dhruv Shah, Dannielle Wellington, Alexander J. Mentzer, Adrienn Angyal, Rebecca Brown, Matthew D. Parker, Zixi Ying, Xuan Yao, Lance Turtle, Susanna Dunachie, Mala K. Maini, Graham Ogg, Julian C. Knight, Yanchun Peng, Sarah L. Rowland-Jones, Tao Dong, David M. Aanensen, Khalil Abudahab, Helen Adams, Alexander Adams, Safiah Afifi, Dinesh Aggarwal, Shazaad S.Y. Ahmad, Louise Aigrain, Adela Alcolea-Medina, Nabil-Fareed Alikhan, Elias Allara, Roberto Amato, Tara Annett, Stephen Aplin, Cristina V. Ariani, Hibo Asad, Amy Ash, Paula Ashfield, Fiona Ashford, Laura Atkinson, Stephen W. Attwood, Cressida Auckland, Alp Aydin, David J. Baker, Paul Baker, Carlos E. Balcazar, Jonathan Ball, Jeffrey C. Barrett, Magdalena Barrow, Edward Barton, Matthew Bashton, Andrew R. Bassett, Rahul Batra, Chris Baxter, Nadua Bayzid, Charlotte Beaver, Angela H. Beckett, Shaun M. Beckwith, Luke Bedford, Robert Beer, Andrew Beggs, Katherine L. Bellis, Louise Berry, Beatrice Bertolusso, Angus Best, Emma Betteridge, David Bibby, Kelly Bicknell, Debbie Binns, Alec Birchley, Paul W. Bird, Chloe Bishop, Rachel Blacow, Victoria Blakey, Beth Blane, Frances Bolt, James Bonfield, Stephen Bonner, David Bonsall, Tim Boswell, Andrew Bosworth, Yann Bourgeois, Olivia Boyd, Declan T. Bradley, Cassie Breen, Catherine Bresner, Judith Breuer, Stephen Bridgett, Iraad F. Bronner, Ellena Brooks, Alice Broos, Julianne R. Brown, Giselda Bucca, Sarah L. Buchan, David Buck, Matthew Bull, Phillipa J. Burns, Shirelle Burton-Fanning, Timothy Byaruhanga, Matthew Byott, Sharon Campbell, Alessandro M. Carabelli, James S. Cargill, Matthew Carlile, Silvia F. Carvalho, Anna Casey, Anibolina Castigador, Jana Catalan, Vicki Chalker, Nicola J. Chaloner, Meera Chand, Joseph G. Chappell, Themoula Charalampous, Wendy Chatterton, Yasmin Chaudhry, Carol M. Churcher, Gemma Clark, Phillip Clarke, Benjamin J. Cogger, Kevin Cole, Jennifer Collins, Rachel Colquhoun, Thomas R. Connor, Kate F. Cook, Jason Coombes, Sally Corden, Claire Cormie, Nicholas Cortes, Marius Cotic, Seb Cotton, Simon Cottrell, Lindsay Coupland, MacGregor Cox, Alison Cox, Noel Craine, Liam Crawford, Aidan Cross, Matthew R. Crown, Dorian Crudgington, Nicola Cumley, Tanya Curran, Martin D. Curran, Ana da Silva Filipe, Gavin Dabrera, Alistair C. Darby, Rose K. Davidson, Alisha Davies, Robert M. Davies, Thomas Davis, Daniela de Angelis, Elen De Lacy, Leonardo de Oliveira Martins, Johnny Debebe, Rebecca Denton-Smith, Samir Dervisevic, Rebecca Dewar, Jayasree Dey, Joana Dias, Donald Dobie, Matthew J. Dorman, Fatima Downing, Megan Driscoll, Louis du Plessis, Nichola Duckworth, Jillian Durham, Kirstine Eastick, Lisa J. Easton, Richard Eccles, Jonathan Edgeworth, Sue Edwards, Kate El Bouzidi, Sahar Eldirdiri, Nicholas Ellaby, Scott Elliott, Gary Eltringham, Leah Ensell, Michelle J. Erkiert, Marina Escalera Zamudio, Sarah Essex, Johnathan M. Evans, Cariad Evans, William Everson, Derek J. Fairley, Karlie Fallon, Arezou Fanaie, Ben W. Farr, Christopher Fearn, Theresa Feltwell, Lynne Ferguson, Laia Fina, Flavia Flaviani, Vicki M. Fleming, Sally Forrest, Ebenezer Foster-Nyarko, Benjamin H. Foulkes, Luke Foulser, Mireille Fragakis, Dan Frampton, Sarah Francois, Christophe Fraser, Timothy M. Freeman, Helen Fryer, Marc Fuchs, William Fuller, Kavitha Gajee, Katerina Galai, Abbie Gallagher, Eileen Gallagher, Michael D. Gallagher, Marta Gallis, Amy Gaskin, Bree Gatica-Wilcox, Lily Geidelberg, Matthew Gemmell, Iliana Georgana, Ryan P. George, Laura Gifford, Lauren Gilbert, Sophia T. Girgis, Sharon Glaysher, Emily J. Goldstein, Tanya Golubchik, Andrea N. Gomes, Sónia Gonçalves, Ian G. Goodfellow, Scott Goodwin, Salman Goudarzi, Marina Gourtovaia, Clive Graham, Lee Graham, Paul R. Grant, Luke R. Green, Angie Green, Jane Greenaway, Richard Gregory, Martyn Guest, Rory N. Gunson, Ravi K. Gupta, Bernardo Gutierrez, Sam T. Haldenby, William L. Hamilton, Samantha E. Hansford, Tanzina Haque, Kathryn A. Harris, Ian Harrison, Ewan M. Harrison, Jennifer Hart, John A. Hartley, William T. Harvey, Matthew Harvey, Mohammed O. Hassan-Ibrahim, Judith Heaney, Thomas Helmer, John H. Henderson, Andrew R. Hesketh, Jessica Hey, David Heyburn, Ellen E. Higginson, Verity Hill, Jack D. Hill, Rachel A. Hilson, Ember Hilvers, Matthew T.G. Holden, Amy Hollis, Christopher W. Holmes, Nadine Holmes, Alison H. Holmes, Richard Hopes, Hailey R. Hornsby, Myra Hosmillo, Catherine Houlihan, Hannah C. Howson-Wells, Jonathan Hubb, Hannah Huckson, Warwick Hughes, Joseph Hughes, Margaret Hughes, Stephanie Hutchings, Giles Idle, Chris J. Illingworth, Robert Impey, Dianne Irish-Tavares, Miren Iturriza-Gomara, Rhys Izuagbe, Chris Jackson, Ben Jackson, Leigh M. Jackson, Kathryn A. Jackson, David K. Jackson, Aminu S. Jahun, Victoria James, Keith James, Christopher Jeanes, Aaron R. Jeffries, Sarah Jeremiah, Andrew Jermy, Michaela John, Rob Johnson, Kate Johnson, Ian Johnston, Owen Jones, Sophie Jones, Hannah Jones, Christopher R. Jones, Neil Jones, Amelia Joseph, Sarah Judges, Gemma L. Kay, Sally Kay, Jon-Paul Keatley, Alexander J. Keeley, Anita Kenyon, Leanne M. Kermack, Manjinder Khakh, Stephen P. Kidd, Maimuna Kimuli, Stuart Kirk, Christine Kitchen, Katie Kitchman, Bridget A. Knight, Cherian Koshy, Moritz U.G. Kraemer, Sara Kumziene-Summerhayes, Dominic Kwiatkowski, Angie Lackenby, Kenneth G. Laing, Temi Lampejo, Cordelia F. Langford, Deborah Lavin, Andrew I. Lawton, Jack Lee, David Lee, Stefanie V. Lensing, Steven Leonard, Lisa J. Levett, Thanh Le-Viet, Jonathan Lewis, Kevin Lewis, Jennifier Liddle, Steven Liggett, Patrick J. Lillie, Michelle M. Lister, Rich Livett, Stephanie Lo, Nicholas J. Loman, Matthew W. Loose, Stavroula F. Louka, Katie F. Loveson, Sarah Lowdon, Hannah Lowe, Helen L. Lowe, Anita O. Lucaci, Catherine Ludden, Jessica Lynch, Ronan A. Lyons, Katrina Lythgoe, Nicholas W. Machin, George MacIntyre-Cockett, Andrew Mack, Ben Macklin, Alasdair Maclean, Emily Macnaughton, Pinglawathee Madona, Mailis Maes, Laurentiu Maftei, Adhyana I.K. Mahanama, Tabitha W. Mahungu, Daniel Mair, Joshua Maksimovic, Cassandra S. Malone, Daniel Maloney, Nikos Manesis, Robin Manley, Anna Mantzouratou, Angela Marchbank, Arun Mariappan, Inigo Martincorena, Rocio T. Martinez Nunez, Alison E. Mather, Patrick Maxwell, Megan Mayhew, Tamyo Mbisa, Clare M. McCann, Shane A. McCarthy, Kathryn McCluggage, Patrick C. McClure, J.T. McCrone, Martin P. McHugh, James P. McKenna, Caoimhe McKerr, Georgina M. McManus, Claire L. McMurray, Claire McMurray, Alan McNally, Lizzie Meadows, Nathan Medd, Oliver Megram, Mirko Menegazzo, Ian Merrick, Stephen L. Michell, Michelle L. Michelsen, Mariyam Mirfenderesky, Jeremy Mirza, Julia Miskelly, Emma Moles-Garcia, Robin J. Moll, Zoltan Molnar, Irene M. Monahan, Matteo Mondani, Siddharth Mookerjee, Christopher Moore, Jonathan Moore, Nathan Moore, Catherine Moore, Helen Morcrette, Sian Morgan, Mari Morgan, Matilde Mori, Arthur Morriss, Samuel Moses, Craig Mower, Peter Muir, Afrida Mukaddas, Florence Munemo, Robert Munn, Abigail Murray, Leanne J. Murray, Darren R. Murray, Manasa Mutingwende, Richard Myers, Eleni Nastouli, Gaia Nebbia, Andrew Nelson, Charlotte Nelson, Sam Nicholls, Jenna Nichols, Roberto Nicodemi, Kyriaki Nomikou, Justin O’Grady, Sarah O'Brien, Mina Odedra, Natasha Ohemeng-Kumi, Karen Oliver, Richard J. Orton, Husam Osman, xeine O'Toole, Nicole Pacchiarini, Debra Padgett, Andrew J. Page, Emily J. Park, Naomi R. Park, Surendra Parmar, David G. Partridge, David Pascall, Amita Patel, Bindi Patel, Steve Paterson, Brendan A.I. Payne, Sharon J. Peacock, Clare Pearson, Emanuela Pelosi, Benita Percival, Jon Perkins, Malorie Perry, Malte L. Pinckert, Steven Platt, Olga Podplomyk, Manoj Pohare, Marcus Pond, Cassie F. Pope, Radoslaw Poplawski, Jessica Powell, Jennifer Poyner, Liam Prestwood, Anna Price, James R. Price, Jacqui A. Prieto, David T. Pritchard, Sophie J. Prosolek, Georgia Pugh, Monika Pusok, Oliver G. Pybus, Hannah M. Pymont, Michael A. Quail, Joshua Quick, Clara Radulescu, Jayna Raghwani, Manon Ragonnet-Cronin, Lucille Rainbow, Diana Rajan, Shavanthi Rajatileka, Newara A. Ramadan, Andrew Rambaut, John Ramble, Paul A. Randell, Paul Randell, Liz Ratcliffe, Veena Raviprakash, Mohammad Raza, Nicholas M. Redshaw, Sara Rey, Nicola Reynolds, Alex Richter, David L. Robertson, Esther Robinson, Samuel C. Robson, Fiona Rogan, Stefan Rooke, Will Rowe, Sunando Roy, Steven Rudder, Chris Ruis, Steven Rushton, Felicity Ryan, Kordo Saeed, Buddhini Samaraweera, Christine M. Sambles, Roy Sanderson, Theo Sanderson, Fei Sang, Thea Sass, Emily Scher, Garren Scott, Carol Scott, Jasveen Sehmi, Sharif Shaaban, Divya Shah, Jessica Shaw, Ekaterina Shelest, James G. Shepherd, Liz A. Sheridan, Nicola Sheriff, Lesley Shirley, John Sillitoe, Siona Silviera, David A. Simpson, Aditi Singh, Dawn Singleton, Timofey Skvortsov, Tim J. Sloan, Graciela Sluga, Ken Smith, Kim S. Smith, Perminder Smith, Darren L. Smith, Louise Smith, Colin P. Smith, Nikki Smith, Katherine L. Smollett, Luke B. Snell, Thomas Somassa, Joel Southgate, Karla Spellman, Michael H. Spencer Chapman, Lewis G. Spurgin, Moira J. Spyer, Rachael Stanley, William Stanley, Thomas D. Stanton, Igor Starinskij, Joanne Stockton, Susanne Stonehouse, Nathaniel Storey, David J. Studholme, Malur Sudhanva, Emma Swindells, Yusri Taha, Ngee Keong Tan, Julian W. Tang, Miao Tang, Ben E.W. Taylor, Joshua F. Taylor, Sarah Taylor, Ben Temperton, Kate E. Templeton, Claire Thomas, Laura Thomson, Emma C. Thomson, Alicia Thornton, Scott A.J. Thurston, John A. Todd, Rachael Tomb, Lily Tong, Gerry Tonkin-Hill, M. Estee Torok, Jaime M. Tovar-Corona, Amy Trebes, Alexander J. Trotter, Ioulia Tsatsani, Robyn Turnbull, Katherine A. Twohig, Helen Umpleby, Anthony P. Underwood, Edith E. Vamos, Tetyana I. Vasylyeva, Sreenu Vattipally, Gabrielle Vernet, Barry B. Vipond, Erik M. Volz, Sarah Walsh, Dennis Wang, Ben Warne, Joanna Warwick-Dugdale, Elizabeth Wastnedge, Joanne Watkins, Louisa K. Watson, Sheila Waugh, Hermione J. Webster, Danni Weldon, Elaine Westwick, Thomas Whalley, Helen Wheeler, Mark Whitehead, Max Whiteley, Andrew Whitwham, Claudia Wierzbicki, Nicholas J. Willford, Lesley-Anne Williams, Rebecca Williams, Cheryl Williams, Chris Williams, Charlotte A. Williams, Rachel J. Williams, Thomas Williams, Catryn Williams, Kathleen A. Williamson, Eleri Wilson-Davies, Eric Witele, Karen T. Withell, Adam A. Witney, Paige Wolverson, Nick Wong, Trudy Workman, Victoria Wright, Derek W. Wright, Tim Wyatt, Sarah Wyllie, Li Xu-McCrae, Mehmet Yavus, Geraldine Yaze, Corin A. Yeats, Gonzalo Yebra, Wen C. Yew, Gregory R. Young, Jamie Young, Alex E. Zarebski, Peijun Zhang, J. Kenneth Baillie, Malcolm G. Semple, Peter J.M. Openshaw, Gail Carson, Beatrice Alex, Petros Andrikopoulos, Benjamin Bach, Wendy S. Barclay, Debby Bogaert, Kanta Chechi, Graham S. Cooke, Annemarie B. Docherty, Gonçalo dos Santos Correia, Marc-Emmanuel Dumas, Jake Dunning, Tom Fletcher, Christopher A. Green, William Greenhalf, Julian L. Griffin, Rishi K. Gupta, Ewen M. Harrison, Julian A. Hiscox, Antonia Ying Wai Ho, Peter W. Horby, Samreen Ijaz, Saye Khoo, Paul Klenerman, Andrew Law, Matthew R. Lewis, Sonia Liggi, Wei Shen Lim, Lynn Maslen, Laura Merson, Alison M. Meynert, Mahdad Noursadeghi, Michael Olanipekun, Anthonia Osagie, Massimo Palmarini, Carlo Palmieri, William A. Paxton, Georgios Pollakis, Nicholas Price, Clark D. Russell, Vanessa Sancho-Shimizu, Caroline J. Sands, Janet T. Scott, Louise Sigfrid, Tom Solomon, Shiranee Sriskandan, David Stuart, Charlotte Summers, Olivia V. Swann, Zoltan Takats, Panteleimon Takis, Richard S. Tedder, A.A. Roger Thompson, Ryan S. Thwaites, Maria Zambon, Hayley Hardwick, Chloe Donohue, Fiona Griffiths, Wilna Oosthuyzen, Cara Donegan, Rebecca G. Spencer, Jo Dalton, Michelle Girvan, Egle Saviciute, Stephanie Roberts, Janet Harrison, Laura Marsh, Marie Connor, Sophie Halpin, Clare Jackson, Carrol Gamble, Daniel Plotkin, James Lee, Gary Leeming, Murray Wham, Sara Clohisey, Ross Hendry, James Scott-Brown, Victoria Shaw, Sarah E. McDonald, Seán Keating, Katie A. Ahmed, Jane A. Armstrong, Milton Ashworth, Innocent G. Asiimwe, Siddharth Bakshi, Samantha L. Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Benjamin W.A. Catterall, Jordan J. Clark, Emily A. Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis W.S. Fisher, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Catherine Hartley, Rebecca L. Jensen, Christopher B. Jones, Trevor R. Jones, Shadia Khandaker, Katharine King, Robyn T. Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, Lara Lavelle-Langham, Daniella Lefteri, Lauren Lett, Lucia A. Livoti, Maria Mancini, Sarah McDonald, Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S. Miah, Joanna Middleton, Joyce Mitchell, Ellen G. Murphy, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, P. Matthew Ridley, Debby Sales, Victoria E. Shaw, Rebecca K. Shears, Benjamin Small, Krishanthi S. Subramaniam, Agnieska Szemiel, Aislynn Taggart, Jolanta Tanianis-Hughes, Jordan Thomas, Erwan Trochu, Libby van Tonder, Eve Wilcock, J. Eunice Zhang, Lisa Flaherty, Nicole Maziere, Emily Cass, Alejandra Doce Carracedo, Nicola Carlucci, Anthony Holmes, Hannah Massey, Lee Murphy, Nicola Wrobel, Sarah McCafferty, Kirstie Morrice, Alan MacLean, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Erin L. Aldera, Ana Alegria, Sam Allen, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin Barlow, Stella Barnass, Nicholas Barrett, Christopher Bassford, Sneha Basude, David Baxter, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Colin Berry, Nicola Best, Pieter Bothma, David Chadwick, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Phil Donnison, Sam Douthwaite, Andrew Drummond, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Chi Eziefula, Chrisopher Fegan, Adam Finn, Duncan Fullerton, Sanjeev Garg, Atul Garg, Effrossyni Gkrania-Klotsas, Jo Godden, Arthur Goldsmith, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B. Hawcutt, Maria Hobrok, Luke Hodgson, Anil Hormis, Michael Jacobs, Susan Jain, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Jason Kendall, Caroline Kerrison, Ian Kerslake, Oliver Koch, Gouri Koduri, George Koshy, Shondipon Laha, Steven Laird, Susan Larkin, Tamas Leiner, Patrick Lillie, James Limb, Vanessa Linnett, Jeff Little, Mark Lyttle, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills, Jane Minton, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick Morgan, Craig Morris, Katherine Mortimore, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Megan Nagel, Thapas Nagarajan, Mark Nelson, Lillian Norris, Matthew K. O'Shea, Igor Otahal, Marlies Ostermann, Mark Pais, Selva Panchatsharam, Danai Papakonstantinou, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Jagtur Singh Pooni, Tim Planche, Frank Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Bobby Ruge, Brendan Ryan, Taranprit Saluja, Matthias L. Schmid, Aarti Shah, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jeremy Sizer, Manu Shankar-Hari, Richard Smith, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Richard Stewart, Pradeep Subudhi, Tamas Szakmany, Kate Tatham, Jo Thomas, Chris Thompson, Robert Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Nick Vallotton, Rama Vancheeswaran, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Padmasayee Papineni, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G. Wootton, Andrew Workman, Bryan Yates, and Peter Young

Subjects
Phylogenetics, Molecular biology, Immunology, Immune response, Virology, Science
Abstract

Summary: We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.

Published
2021
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6. Deep convolutional neural networks: Outperforming established algorithms in the evaluation of industrial optical coherence tomography (OCT) images of pharmaceutical coatings

Author

Matthias Wolfgang, Michael Weißensteiner, Phillip Clarke, Wen-Kai Hsiao, and Johannes G. Khinast

Subjects
Convolutional neural networks (CNNs), Optical coherence tomography (OCT), Image segmentation, Coating layer thickness, Single- and multi-layered coatings, Pharmacy and materia medica, RS1-441
Abstract

This paper presents a novel evaluation approach for optical coherence tomography (OCT) image analysis of pharmaceutical solid dosage forms based on deep convolutional neural networks (CNNs). As a proof of concept, CNNs were applied to image data from both, in- and at-line OCT implementations, monitoring film-coated tablets as well as single- and multi-layered pellets. CNN results were compared against results from established algorithms based on ellipse-fitting, as well as to human-annotated ground truth data. Performance benchmarks used include, efficiency (computation speed), sensitivity (number of detections from a defined test set) and accuracy (deviation from the reference method). The results were validated by comparing the output of several algorithms to data manually annotated by human experts and microscopy images of cross-sectional cuts of the same dosage forms as a reference method. In order to guarantee comparability for all results, the algorithms were executed on the same hardware. Since modern OCT systems must operate under real-time conditions in order to be implemented in-line into manufacturing lines, the necessary steps are discussed on how to achieve this goal without sacrificing the algorithmic performance and how to tailor a deep CNN to cope with the high amount of image noise and alterations in object appearance. The developed deep learning approach outperforms static algorithms currently available in pharma applications with respect to performance benchmarks, and represents the next level in real time evaluation of challenging industrial OCT image data.

Published
2020
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7. Revisiting the 'Christmas Holiday Effect' in the Southern Hemisphere

Author

Josh Knight, Chris Schilling, Adrian Barnett, Rod Jackson, and Phillip Clarke

Subjects
Christmas effect, holiday effect, seasonal mortality, seasonal variation, seasons, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

BackgroundA “Christmas holiday effect” showing elevated cardiovascular mortality over the Christmas holidays (December 25 to January 7) was demonstrated previously in study from the United States. To separate the effect of seasonality from any holiday effect, a matching analysis was conducted for New Zealand, where the Christmas holiday period falls within the summer season. Methods and ResultsNew Zealand mortality data for a 25‐year period (1988–2013) was analyzed based on the same methodology used in the previous study. Locally weighted smoothing was used to calculate an “expected” number of deaths for each day of the year. The expected value was compared with the actual number of deaths. In addition, mean age at death was estimated and used to assess the life‐years lost due to excess mortality. There were 738 409 deaths (197 109 coded as cardiac deaths) during the period. We found evidence of a Christmas holiday effect in our of medical facility's cardiac deaths, with an excess event rate of 4.2% (95% CI 0.7–7.7%) leading to ≈4 additional deaths per annum. The average age of those with fatal cardiac deaths was 76.8 years (SD 13.5) during the Christmas holiday period, resulting in 148 to 222 years of life lost per annum. ConclusionsCardiac mortality is elevated during the Christmas holiday period relative to surrounding time periods. Our findings are consistent with a previously reported study conducted in the United States, suggesting that cardiac mortality does not take a “summer break.”

Published
2016
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9. Flash glucose monitoring for indigenous Australians with type 2 diabetes: a randomised pilot and feasibility study

Author

Digsu Koye, Elif Ekinci, Audrey Eer, Mariam Hachem, Tracey Hearn, Sharon Atkinson-Briggs, Jessica Jones, Sandra Eades, Sabine Braat, Stephen Twigg, Ashim Sinha, Anna McLean, Richard O'Brien, Phillip Clarke, David O'Neal, David Story, Jeffrey Zajac, Megan Freund, Ray Kelly, and Luke Burchill

Subjects
Health (social science), Epidemiology, Health Policy, Public Health, Environmental and Occupational Health, Medicine (miscellaneous), Health Informatics
Published
2023

10. Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Author

S. Cotton, M.P. McHugh, R. Dewar, J.G. Haas, K. Templeton, Samuel C. Robson, Thomas R. Connor, Nicholas J. Loman, Tanya Golubchik, Rocio T. Martinez Nunez, David Bonsall, Andrew Rambaut, Luke B. Snell, Rich Livett, Catherine Ludden, Sally Corden, Eleni Nastouli, Gaia Nebbia, Ian Johnston, Jacqui A. Prieto, Kordo Saeed, David K. Jackson, Catherine Houlihan, Dan Frampton, William L. Hamilton, Adam A. Witney, Giselda Bucca, Cassie F. Pope, Catherine Moore, Emma C. Thomson, Teresa Cutino-Moguel, Ewan M. Harrison, Colin P. Smith, Fiona Rogan, Shaun M. Beckwith, Abigail Murray, Dawn Singleton, Kirstine Eastick, Liz A. Sheridan, Paul Randell, Leigh M. Jackson, Cristina V. Ariani, Sónia Gonçalves, Derek J. Fairley, Matthew W. Loose, Joanne Watkins, Samuel Moses, Sam Nicholls, Matthew Bull, Roberto Amato, Darren L. Smith, David M. Aanensen, Jeffrey C. Barrett, Beatrix Kele, Dinesh Aggarwal, James G. Shepherd, Martin D. Curran, Surendra Parmar, Matthew D. Parker, Catryn Williams, Sharon Glaysher, Anthony P. Underwood, Matthew Bashton, Nicole Pacchiarini, Katie F. Loveson, Matthew Byott, Alessandro M. Carabelli, Kate E. Templeton, Sharon J. Peacock, Thushan I. de Silva, Dennis Wang, Cordelia F. Langford, John Sillitoe, Rory N. Gunson, Simon Cottrell, Justin O’Grady, Dominic Kwiatkowski, Patrick J. Lillie, Nicholas Cortes, Nathan Moore, Claire Thomas, Phillipa J. Burns, Tabitha W. Mahungu, Steven Liggett, Angela H. Beckett, Matthew TG. Holden, Lisa J. Levett, Husam Osman, Mohammed O. Hassan-Ibrahim, David A. Simpson, Meera Chand, Ravi K. Gupta, Alistair C. Darby, Steve Paterson, Oliver G. Pybus, Erik M. Volz, Daniela de Angelis, David L. Robertson, Andrew J. Page, Inigo Martincorena, Louise Aigrain, Andrew R. Bassett, Nick Wong, Yusri Taha, Michelle J. Erkiert, Michael H. Spencer Chapman, Rebecca Dewar, Martin P. McHugh, Siddharth Mookerjee, Stephen Aplin, Matthew Harvey, Thea Sass, Helen Umpleby, Helen Wheeler, James P. McKenna, Ben Warne, Joshua F. Taylor, Yasmin Chaudhry, Rhys Izuagbe, Aminu S. Jahun, Gregory R. Young, Claire McMurray, Clare M. McCann, Andrew Nelson, Scott Elliott, Hannah Lowe, Anna Price, Matthew R. Crown, Sara Rey, Sunando Roy, Ben Temperton, Sharif Shaaban, Andrew R. Hesketh, Kenneth G. Laing, Irene M. Monahan, Judith Heaney, Emanuela Pelosi, Siona Silviera, Eleri Wilson-Davies, Helen Fryer, Helen Adams, Louis du Plessis, Rob Johnson, William T. Harvey, Joseph Hughes, Richard J. Orton, Lewis G. Spurgin, Yann Bourgeois, Chris Ruis, Áine O'Toole, Marina Gourtovaia, Theo Sanderson, Christophe Fraser, Jonathan Edgeworth, Judith Breuer, Stephen L. Michell, John A. Todd, Michaela John, David Buck, Kavitha Gajee, Gemma L. Kay, David Heyburn, Themoula Charalampous, Adela Alcolea-Medina, Katie Kitchman, Alan McNal, David T. Pritch, Samir Dervisevic, Peter Muir, Esther Robinson, Barry B. Vipond, Newara A. Ramadan, Christopher Jeanes, Danni Weldon, Jana Catalan, Neil Jones, Ana da Silva Filipe, Chris Williams, Marc Fuchs, Julia Miskelly, Aaron R. Jeffries, Karen Oliver, Naomi R. Park, Amy Ash, Cherian Koshy, Magdalena Barrow, Sarah L. Buchan, Anna Mantzouratou, Gemma Clark, Christopher W. Holmes, Sharon Campbell, Thomas Davis, Ngee Keong Tan, Julianne R. Brown, Kathryn A. Harris, Stephen P. Kidd, Paul R. Grant, Li Xu-McCrae, Alison Cox, Pinglawathee Madona, Marcus Pond, Paul A. Randell, Karen T. Withell, Cheryl Williams, Clive Graham, Rebecca Denton-Smith, Emma Swindells, Robyn Turnbull, Tim J. Sloan, Andrew Bosworth, Stephanie Hutchings, Hannah M. Pymont, Anna Casey, Liz Ratcliffe, Christopher R. Jones, Bridget A. Knight, Tanzina Haque, Jennifer Hart, Dianne Irish-Tavares, Eric Witele, Craig Mower, Louisa K. Watson DipHE, Jennifer Collins, Gary Eltringham, Dorian Crudgington, Ben Macklin, Miren Iturriza-Gomara, Anita O. Lucaci, Patrick C. McClure, Matthew Carlile, Nadine Holmes, Christopher Moore, Nathaniel Storey, Stefan Rooke, Gonzalo Yebra, Noel Craine, Malorie Perry, Nabil-Fareed Alikhan, Stephen Bridgett, Kate F. Cook, Christopher Fearn, Salman Goudarzi, Ronan A. Lyons, Thomas Williams, Sam T. Haldenby, Jillian Durham, Steven Leonard, Robert M. Davies, Rahul Batra, Beth Blane, Moira J. Spyer, Perminder Smith, Mehmet Yavus, Rachel J. Williams, Adhyana IK. Mahanama, Buddhini Samaraweera, Sophia T. Girgis, Samantha E. Hansford, Angie Green, Charlotte Beaver, Katherine L. Bellis, Matthew J. Dorman, Sally Kay, Liam Prestwood, Shavanthi Rajatileka, Joshua Quick, Radoslaw Poplawski, Nicola Reynolds, Andrew Mack, Arthur Morriss, Thomas Whalley, Bindi Patel, Iliana Georgana, Myra Hosmillo, Malte L. Pinckert, Joanne Stockton, John H. Henderson, Amy Hollis, William Stanley, Wen C. Yew, Richard Myers, Alicia Thornton, Alexander Adams, Tara Annett, Hibo Asad, Alec Birchley, Jason Coombes, Johnathan M. Evans, Laia Fina, Bree Gatica-Wilcox, Lauren Gilbert, Lee Graham, Jessica Hey, Ember Hilvers, Sophie Jones, Hannah Jones, Sara Kumziene-Summerhayes, Caoimhe McKerr, Jessica Powell, Georgia Pugh, Sarah Taylor, Alexander J. Trotter, Charlotte A. Williams, Leanne M. Kermack, Benjamin H. Foulkes, Marta Gallis, Hailey R. Hornsby, Stavroula F. Louka, Manoj Pohare, Paige Wolverson, Peijun Zhang, George MacIntyre-Cockett, Amy Trebes, Robin J. Moll, Lynne Ferguson, Emily J. Goldstein, Alasdair Maclean, Rachael Tomb, Igor Starinskij, Laura Thomson, Joel Southgate, Moritz UG. Kraemer, Jayna Raghwani, Alex E. Zarebski, Olivia Boyd, Lily Geidelberg, Chris J. Illingworth, Chris Jackson, David Pascall, Sreenu Vattipally, Timothy M. Freeman, Sharon N. Hsu, Benjamin B. Lindsey, Keith James, Kevin Lewis, Gerry Tonkin-Hill, Jaime M. Tovar-Corona, MacGregor Cox, Khalil Abudahab, Mirko Menegazzo, Ben EW. Taylor, Corin A. Yeats, Afrida Mukaddas, Derek W. Wright, Leonardo de Oliveira Martins, Rachel Colquhoun, Verity Hill, Ben Jackson, J.T. McCrone, Nathan Medd, Emily Scher, Jon-Paul Keatley, Tanya Curran, Sian Morgan, Patrick Maxwell, Ken Smith, Sahar Eldirdiri, Anita Kenyon, Alison H. Holmes, James R. Price, Tim Wyatt, Alison E. Mather, Timofey Skvortsov, John A. Hartley, Martyn Guest, Christine Kitchen, Ian Merrick, Robert Munn, Beatrice Bertolusso, Jessica Lynch, Gabrielle Vernet, Stuart Kirk, Elizabeth Wastnedge, Rachael Stanley, Giles Idle, Declan T. Bradley, Nicholas F. Killough, Jennifer Poyner, Matilde Mori, Owen Jones, Victoria Wright, Ellena Brooks, Carol M. Churcher, Laia Delgado Callico, Mireille Fragakis, Katerina Galai, Andrew Jermy, Sarah Judges, Anna Markov, Georgina M. McManus, Kim S. Smith, Peter MD. Thomas-McEwen, Elaine Westwick, Stephen W. Attwood, Frances Bolt, Alisha Davies, Elen De Lacy, Fatima Downing, Sue Edwards, Lizzie Meadows, Sarah Jeremiah, Nikki Smith, Luke Foulser, Amita Patel, Louise Berry, Tim Boswell, Vicki M. Fleming, Hannah C. Howson-Wells, Amelia Joseph, Manjinder Khakh, Michelle M. Lister, Paul W. Bird, Karlie Fallon, Thomas Helmer, Claire L. McMurray, Mina Odedra, Jessica Shaw, Julian W. Tang, Nicholas J. Willford, Victoria Blakey, Veena Raviprakash, Nicola Sheriff, Lesley-Anne Williams, Theresa Feltwell, Luke Bedford, James S. Cargill, Warwick Hughes, Jonathan Moore, Susanne Stonehouse, Laura Atkinson, Jack CD. Lee, Divya Shah, Natasha Ohemeng-Kumi, John Ramble, Jasveen Sehmi, Rebecca Williams, Wendy Chatterton, Monika Pusok, William Everson, Anibolina Castigador, Emily Macnaughton, Kate El Bouzidi, Temi Lampejo, Malur Sudhanva, Cassie Breen, Graciela Sluga, Shazaad SY. Ahmad, Ryan P. George, Nicholas W. Machin, Debbie Binns, Victoria James, Rachel Blacow, Lindsay Coupland, Louise Smith, Edward Barton, Debra Padgett, Garren Scott, Aidan Cross, Mariyam Mirfenderesky, Jane Greenaway, Kevin Cole, Phillip Clarke, Nichola Duckworth, Sarah Walsh, Kelly Bicknell, Robert Impey, Sarah Wyllie, Richard Hopes, Chloe Bishop, Vicki Chalker, Ian Harrison, Laura Gifford, Zoltan Molnar, Cressida Auckland, Cariad Evans, Kate Johnson, David G. Partridge, Mohammad Raza, Paul Baker, Stephen Bonner, Sarah Essex, Leanne J. Murray, Andrew I. Lawton, Shirelle Burton-Fanning, Brendan AI. Payne, Sheila Waugh, Andrea N. Gomes, Maimuna Kimuli, Darren R. Murray, Paula Ashfield, Donald Dobie, Fiona Ashford, Angus Best, Liam Crawford, Nicola Cumley, Megan Mayhew, Oliver Megram, Jeremy Mirza, Emma Moles-Garcia, Benita Percival, Megan Driscoll, Leah Ensell, Helen L. Lowe, Laurentiu Maftei, Matteo Mondani, Nicola J. Chaloner, Benjamin J. Cogger, Lisa J. Easton, Hannah Huckson, Jonathan Lewis, Sarah Lowdon, Cassandra S. Malone, Florence Munemo, Manasa Mutingwende, Roberto Nicodemi, Olga Podplomyk FD, Thomas Somassa, Andrew Beggs, Alex Richter, Claire Cormie, Joana Dias, Sally Forrest, Ellen E. Higginson, Mailis Maes, Jamie Young, Rose K. Davidson, Kathryn A. Jackson, Alexander J. Keeley, Jonathan Ball, Timothy Byaruhanga, Joseph G. Chappell, Jayasree Dey, Jack D. Hill, Emily J. Park, Arezou Fanaie, Rachel A. Hilson, Geraldine Yaze, Stephanie Lo, Safiah Afifi, Robert Beer, Joshua Maksimovic, Kathryn McCluggage, Karla Spellman, Catherine Bresner, William Fuller, Angela Marchbank, Trudy Workma, Ekaterina Shelest, Johnny Debebe, Fei Sang, Sarah Francois, Bernardo Gutierrez, Tetyana I. Vasylyeva, Flavia Flaviani, Manon Ragonnet-Cronin, Katherine L. Smollett, Alice Broos, Daniel Mair, Jenna Nichols, Kyriaki Nomikou, Lily Tong, Ioulia Tsatsani, Sarah O'Brien, Steven Rushton, Roy Sanderson, Jon Perkins, Seb Cotton, Abbie Gallagher, Elias Allara, Clare Pearson, David Bibby, Gavin Dabrer, Nicholas Ellaby, Eileen Gallagher, Jonathan Hubb, Angie Lackenby, David Lee, Nikos Manesis, Tamyo Mbisa, Steven Platt, Katherine A. Twohig, Mari Morgan, Alp Aydin, David J. Baker, Ebenezer Foster-Nyarko, Sophie J. Prosolek, Steven Rudder, Chris Baxter, Sílvia F. Carvalho, Deborah Lavin, Arun Mariappan, Clara Radulescu, Aditi Singh, Miao Tang, Helen Morcrette, Nadua Bayzid, Marius Cotic, Carlos E. Balcazar, Michael D. Gallagher, Daniel Maloney, Thomas D. Stanton, Kathleen A. Williamson, Robin Manley, Michelle L. Michelsen, Christine M. Sambles, David J. Studholme, Joanna Warwick-Dugdale, Richard Eccles, Matthew Gemmell, Richard Gregory, Margaret Hughes, Charlotte Nelson, Lucille Rainbow, Edith E. Vamos, Hermione J. Webster, Mark Whitehead, Claudia Wierzbicki, Adrienn Angyal, Luke R. Green, Max Whiteley, Emma Betteridge, Iraad F. Bronner, Ben W. Farr, Scott Goodwin, Stefanie V. Lensing, Shane A. McCarthy, Michael A. Quail, Diana Rajan, Nicholas M. Redshaw, Carol Scott, Lesley Shirley, Scott AJ. Thurston, Will Rowe, Amy Gaskin, Thanh Le-Viet, James Bonfield, Jennifier Liddle, Andrew Whitwham, University of St Andrews. School of Medicine, University of St Andrews. Infection and Global Health Division, and Apollo - University of Cambridge Repository

Subjects
Microbiology (medical), MCC, Introduction, SARS-CoV-2, NDAS, COVID-19, Care homes, General Medicine, NIS, Patient Discharge, Hospitals, Hospitalization, Infectious Diseases, SDG 3 - Good Health and Well-being, RA0421, RA0421 Public health. Hygiene. Preventive Medicine, Humans, Hospital discharge
Abstract

COG-UK is supported by funding from the MRC part of UK Research & Innovation, the National Institute of Health Research (Grant code MC_PC_19027), and Genome Research Limited, operating as the Welcome Sanger Institute. Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine. Publisher PDF

Published
2023

11. Synthesis, characterisation and evaluation of hyperbranched N-(2-hydroxypropyl) methacrylamides for transport and delivery in pancreatic cell lines in vitro and in vivo

Author

Akosua B. Anane-Adjei, Nicholas L. Fletcher, Robert J. Cavanagh, Zachary H. Houston, Theodore Crawford, Amanda K. Pearce, Vincenzo Taresco, Alison A. Ritchie, Phillip Clarke, Anna M. Grabowska, Paul R. Gellert, Marianne B. Ashford, Barrie Kellam, Kristofer J. Thurecht, and Cameron Alexander

Subjects
Biomedical Engineering, General Materials Science
Abstract

Hyperbranched polyHPMA materials penetrate deep into pancreatic cancer spheroids and a hyperbranched polymer-gemcitabine conjugate showed potency in vitro and in vivo.

Published
2022

12. The good, the bad and the rebels

Author

Wayne Sharrocks, Joe Glenton, Matthew Hoh, and Phillip Clarke

Subjects
History, Sociology and Political Science, Political science, Political Science and International Relations, Media studies, Management Science and Operations Research, Form of the Good, Law, Social Sciences (miscellaneous), Theme (narrative)
Abstract

In November 2016 Veterans for Peace UK held a public conference on the theme, ‘Creating Enemies: Critical perspectives on the justification of war’.1 The first part of the conference drew on histor...

Published
2019

13. Deep convolutional neural networks: Outperforming established algorithms in the evaluation of industrial optical coherence tomography (OCT) images of pharmaceutical coatings

Author

Johannes Khinast, Wen-Kai Hsiao, Michael Weißensteiner, Matthias Wolfgang, and Phillip Clarke

Subjects
Optical coherence tomography (OCT), Ground truth, Image segmentation, medicine.diagnostic_test, Computer science, business.industry, Deep learning, lcsh:RS1-441, Pharmaceutical Science, Convolutional neural network, Convolutional neural networks (CNNs), lcsh:Pharmacy and materia medica, Optical coherence tomography, Proof of concept, Single- and multi-layered coatings, Test set, medicine, Image noise, Artificial intelligence, business, Algorithm, Coating layer thickness, Research Paper
Abstract

This paper presents a novel evaluation approach for optical coherence tomography (OCT) image analysis of pharmaceutical solid dosage forms based on deep convolutional neural networks (CNNs). As a proof of concept, CNNs were applied to image data from both, in- and at-line OCT implementations, monitoring film-coated tablets as well as single- and multi-layered pellets. CNN results were compared against results from established algorithms based on ellipse-fitting, as well as to human-annotated ground truth data. Performance benchmarks used include, efficiency (computation speed), sensitivity (number of detections from a defined test set) and accuracy (deviation from the reference method). The results were validated by comparing the output of several algorithms to data manually annotated by human experts and microscopy images of cross-sectional cuts of the same dosage forms as a reference method. In order to guarantee comparability for all results, the algorithms were executed on the same hardware. Since modern OCT systems must operate under real-time conditions in order to be implemented in-line into manufacturing lines, the necessary steps are discussed on how to achieve this goal without sacrificing the algorithmic performance and how to tailor a deep CNN to cope with the high amount of image noise and alterations in object appearance. The developed deep learning approach outperforms static algorithms currently available in pharma applications with respect to performance benchmarks, and represents the next level in real time evaluation of challenging industrial OCT image data., Graphical abstract Unlabelled Image

Published
2020

15. Coal mine dust lung disease in the modern era

Author

Brian Plush, Timothy S. C. Hinks, Phillippe Lachapelle, Louis Irving, Phillip Clarke, Jennifer L. Perret, Shyamali C. Dharmage, Pat Brady, Alastair G. Stewart, and Clare Walter

Subjects
Pulmonary and Respiratory Medicine, Anthracosis, medicine.medical_specialty, business.industry, Progressive massive fibrosis, Pneumoconiosis, Coal mining, medicine.disease, Coal dust, complex mixtures, 030210 environmental & occupational health, respiratory tract diseases, 03 medical and health sciences, 0302 clinical medicine, Environmental health, Epidemiology, medicine, Global health, Coal, 030212 general & internal medicine, business
Abstract

Coal workers' pneumoconiosis (CWP), as part of the spectrum of coal mine dust lung disease (CMDLD), is a preventable but incurable lung disease that can be complicated by respiratory failure and death. Recent increases in coal production from the financial incentive of economic growth lead to higher respirable coal and quartz dust levels, often associated with mechanization of longwall coal mining. In Australia, the observed increase in the number of new CWP diagnoses since the year 2000 has necessitated a review of recommended respirable dust exposure limits, where exposure limits and monitoring protocols should ideally be standardized. Evidence that considers the regulation of engineering dust controls in the mines is lacking even in high-income countries, despite this being the primary preventative measure. Also, it is a global public health priority for at-risk miners to be systemically screened to detect early changes of CWP and to include confirmed patients within a central registry; a task limited by financial constraints in less developed countries. Characteristic X-ray changes are usually categorized using the International Labour Office classification, although future evaluation by low-dose HRCT) chest scanning may allow for CWP detection and thus avoidance of further exposure, at an earlier stage. Preclinical animal and human organoid-based models are required to explore potential re-purposing of anti-fibrotic and related agents with potential efficacy. Epidemiological patterns and the assessment of molecular and genetic biomarkers may further enhance our capacity to identify susceptible individuals to the inhalation of coal dust in the modern era.

Published
2017

16. A mechanically-engineered spray to increase brain penetration of chemotherapeutic nanoparticles in the treatment of high-grade gliomas

Author

Phoebe McCrorie, Vincenco Taresco, Zeyuan Xu, Alison Ritchie, Phillip Clarke, Maria Marlow, and Ruman Rahman

Subjects
Cancer Research, Abstracts, Oncology, Neurology (clinical)
Abstract

Design and implementation of innovative local drug delivery systems (DDS) may overcome current limitations in GBM treatment, such as the lack of therapeutic drug concentrations reaching residual GBM cells following surgery. Here we describe a novel DDS which utilises a bespoke mechanically engineered spray device, designed for safe surgical use, to deliver a mucoadhesive hydrogel containing chemotherapeutic nanoparticles (NPs) into the tumour resection margins. The overall aim is to spray a NP and polymer solution onto the resection cavity and potentially increase penetration of anti-cancer drugs within the 2 cm reoccurrence zone beyond the infiltrative margin. The mucoadhesive gel of choice, pectin, is currently used in other in vivo applications; however we have repurposed this for the brain. Pectin is biocompatible with GBM and human astrocyte cells in vitro and showed neither toxicity nor inflammation for up to 2 weeks upon orthotopic brain injection. Pectin is biodegradable in artificial CSF and is capable of being sprayed from the engineered device. A panel of polymeric, oil-based and polymer-coated NPs have been developed and optimised to maximise drug encapsulation of etoposide and olaparib as proof-of-concept for combination drug delivery. Etoposide/olaparib was chosen due to cytotoxicity from 5 GBM cell lines, including primary lines isolated from the invasive tumour margin (Mean IC50 of 1.1 µM and 8.3 µM respectively). The optimal NP/drug formulation (based on drug encapsulation, spray capability and bio-adhesiveness) will ultimately be assessed for tolerability and efficacy using orthotopic allograft and xenograft high-grade glioma models.

Published
2019

17. Radiative transfer in turbulent flow using spacetime discontinuous Galerkin finite element method

Author

Saba Mudaliar, Phillip Clarke, and Reza Abedi

Subjects
Physics, Polynomial, 010401 analytical chemistry, Mathematical analysis, 020206 networking & telecommunications, 02 engineering and technology, Mixed finite element method, Method of moments (statistics), 01 natural sciences, Finite element method, 0104 chemical sciences, Discontinuous Galerkin method, 0202 electrical engineering, electronic engineering, information engineering, Radiative transfer, Time domain, ComputingMethodologies_COMPUTERGRAPHICS, Extended finite element method
Abstract

The radiative transfer equation for a problem that involves scattering, absorption and radiation is solved using spacetime discontinuous Galerkin (SDG) method. The strength of finite element method to handle scattering problems in heterogeneous media with complex geometries is well known. Adaptive operations in spacetime facilitates very accurate and efficient solution algorithm. We investigated the accuracy of the SDG method by using the method of manufactured solutions. For the case of harmonic phase functions we illustrate how the L2 norm error decreases with the choice of high order polynomial and more refined element size. Key merits of the use of SDG for our problem enamates from its linear solution cost, and the ability to obtain the solution for a wide frequency spectrum in one time domain simulation.

Published
2017

18. Time to publication for publicly funded clinical trials in Australia: an observational study

Author

Adrian G. Barnett, Nicholas Graves, Phillip Clarke, and Linn B Strand

Subjects
medicine.medical_specialty, Biomedical Research, MEDLINE, Alternative medicine, 030204 cardiovascular system & hematology, Time, 03 medical and health sciences, 0302 clinical medicine, Medicine, Humans, 030212 general & internal medicine, Randomized Controlled Trials as Topic, Protocol (science), National health, Publishing, business.industry, Research, Australia, General Medicine, Survival Analysis, Clinical trial, Family medicine, Observational study, Periodicals as Topic, business
Abstract

Objective: To examine the length of time between receiving funding and publishing the protocol and main paper for randomised controlled trials. Design: An observational study using survival analysis. Setting: Publicly funded health and medical research in Australia. Participants: Randomised controlled trials funded by the National Health and Medical Research Council of Australia between 2008 and 2010. Main outcome measures: Time from funding to the protocol paper and main results paper. Multiple variable survival models examining whether study characteristics predicted publication times. Results: We found 77 studies with a total funding of $A59 million. The median time to publication of the protocol paper was 6.4 years after funding (95% CI 4.1 to 8.1). The proportion with a published protocol paper 8 years after funding was 0.61 (95% CI 0.48 to 0.74). The median time to publication of the main results paper was 7.1 years after funding (95% CI 6.3 to 7.6). The proportion with a published main results paper 8 years after funding was 0.72 (95% CI 0.56 to 0.87). The HRs for how study characteristics might influence timing were generally close to one with narrow CIs, the notable exception was that a longer study length lengthened the time to the main paper (HR=0.62 per extra study year, 95% CI 0.43 to 0.89). Conclusions: Despite the widespread registration of clinical trials, there remain serious concerns of trial results not being published or being published with a long delay. We have found that these same concerns apply to protocol papers, which should be publishable soon after funding. Funding agencies could set a target of publishing the protocol paper within 18 months of funding. © Published by the BMJ Publishing Group Limited.This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

Published
2017

19. Revisiting the 'Christmas Holiday Effect' in the Southern Hemisphere

Author

Adrian G. Barnett, Rod Jackson, Josh Knight, Chris Schilling, and Phillip Clarke

Subjects
Male, Epidemiology, Christmas effect, 030204 cardiovascular system & hematology, Cardiac mortality, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Cause of Death, Vascular Disease, holiday effect, Medicine, Humans, 030212 general & internal medicine, Southern Hemisphere, Cardiovascular mortality, Cause of death, Aged, Holidays, Retrospective Studies, Original Research, Excess mortality, Aged, 80 and over, seasonal mortality, seasonal variation, seasons, business.industry, Middle Aged, Lifestyle, United States, Summer season, Mortality data, Cardiovascular Diseases, Female, Mortality/Survival, Cardiology and Cardiovascular Medicine, business, Cardiac deaths, Demography, New Zealand
Abstract

Background A “Christmas holiday effect” showing elevated cardiovascular mortality over the Christmas holidays (December 25 to January 7) was demonstrated previously in study from the United States. To separate the effect of seasonality from any holiday effect, a matching analysis was conducted for New Zealand, where the Christmas holiday period falls within the summer season. Methods and Results New Zealand mortality data for a 25‐year period (1988–2013) was analyzed based on the same methodology used in the previous study. Locally weighted smoothing was used to calculate an “expected” number of deaths for each day of the year. The expected value was compared with the actual number of deaths. In addition, mean age at death was estimated and used to assess the life‐years lost due to excess mortality. There were 738 409 deaths (197 109 coded as cardiac deaths) during the period. We found evidence of a Christmas holiday effect in our of medical facility's cardiac deaths, with an excess event rate of 4.2% (95% CI 0.7–7.7%) leading to ≈4 additional deaths per annum. The average age of those with fatal cardiac deaths was 76.8 years ( SD 13.5) during the Christmas holiday period, resulting in 148 to 222 years of life lost per annum. Conclusions Cardiac mortality is elevated during the Christmas holiday period relative to surrounding time periods. Our findings are consistent with a previously reported study conducted in the United States , suggesting that cardiac mortality does not take a “summer break.”

Published
2016

20. Cost effectiveness of inpatient initiated varenicline tartrate (VT) plus counselling compared to counselling alone: 2 year follow-up of the Smoking Termination Opportunity for inPatients (STOP) study

Author

Malcolm P Brinn, Adrian Esterman, Kristin V Carson, Brian J. Smith, Phillip Clarke, Matthew J. Peters, Kim Dalziel, and Foruhar Moayeri

Subjects
Pediatrics, medicine.medical_specialty, business.industry, Post discharge, Cost effectiveness, medicine.medical_treatment, Quality-adjusted life year, Varenicline Tartrate, Pharmacotherapy, Quitline, Statistical significance, medicine, Smoking cessation, business
Abstract

Background: VT is currently the most effective smoking cessation pharmacotherapy available, yet its cost-effectiveness is unknown.Aims: To conduct a cost-effectiveness analysis for the use of VT in the inpatient setting.Methods: Adult smokers (n=392, 20-75 years) admitted to three metropolitan tertiary hospitals, were randomised to receive either 12-weeks of VT (titrated from 0.5mg daily to 1mg twice-daily) plus Quitline- a phone counselling service (C)(n=196) or C alone (n=196) with completion of the 12 week intervention post discharge. Two year follow-up information was combined with Markov model forecasts to quantify long-term impacts of trial outcome (i.e. observed quit rates) on costs and quality adjusted life year (QALY) gained.Results: At 2 years, there was a cost of $3,278 per additional person classified as an ex-smoker for the VT+C arm compared to the C arm. Incremental cost-effectiveness of hospital costs over a lifetime for VT+C compared to C was $26,688 per QALY. For the outcome of continuous abstinence at 12-months, the proportion of successful subjects in the VT+C arm was significantly greater with 31.1% (n=61) compared to 21.4% (n=42) in the QCA arm (RR 1.45, 95%CI 1.03 to 2.04, p=0.03). Statistical significance was maintained at 24 month follow-up (28.6 for VT+C group compared to 18.4% for QCA group; p=0.01).Conclusion: The trial effects modelled over a lifetime indicated that VT+C compared to C costs an estimated $28,688/QALY gained, which is cost-effective compared to many conventionally accepted therapies.

Published
2016

21. A randomized-controlled trial of high- or low-volume intravenous Plasma-Lyte(®) to prevent hypotension during sedation for colonoscopy

Author

Kate Leslie, Phillip Clarke, Austin Lee, and Megan Allen

Subjects
Adult, Male, medicine.medical_specialty, Sodium Acetate, Sedation, Magnesium Chloride, Colonoscopy, Blood Pressure, Sodium Chloride, Gluconates, law.invention, Potassium Chloride, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Double-Blind Method, law, Anesthesiology, medicine, Humans, Anesthesia, Aged, medicine.diagnostic_test, Dose-Response Relationship, Drug, business.industry, Incidence (epidemiology), 030208 emergency & critical care medicine, General Medicine, Odds ratio, Middle Aged, Confidence interval, Surgery, Anesthesiology and Pain Medicine, Blood pressure, 030211 gastroenterology & hepatology, Female, medicine.symptom, Hypotension, business
Abstract

The purpose of this study was to compare the incidence of hypotension during sedation in adults presenting for elective colonoscopy and randomized to intravenous Plasma-Lyte 148® at either 2 mL·kg−1 (low volume) or 20 mL·kg−1 (high volume). Patients aged ≥ 18 yr presenting for elective colonoscopy, with or without gastroscopy, after oral bowel preparation were randomized to receive the intervention immediately before the start of the procedure. Hypotension was defined as a ≥ 25% decrease in systolic blood pressure (SBP) from baseline during the procedure. Secondary outcomes included SBP < 90 mmHg, lowest SBP during sedation, duration of hypotension, use of vasopressors, postoperative outcomes, and cost. Seventy-five patients were randomly allocated to either the low-volume or high-volume group, respectively (total n = 150). The incidence of hypotension was similar in the two groups (59% vs 56%, respectively; odds ratio, 0.90; 95% confidence interval, 0.47 to 1.71; P = 0.74). The incidence of SBP < 90 mmHg, the lowest SBP during sedation, the duration of hypotension, the use of vasopressors, and postoperative outcomes were also similar in the two groups. This study does not support the routine use of 20 mL·kg−1 of intravenous Plasma-Lyte 148 to prevent hypotension and other complications during sedation for elective colonoscopy in adult patients. Clinical Trials Registry (ANZCTR 12615001288516).

Published
2016

22. The synthesis of 1,2,3,4-tetrahydro-2,2-dimethylquinolin-4-ones as antioxidant precursors

Author

Ian Phillip Clarke and Otto Meth-Cohn

Subjects
Fluorobenzenes, chemistry.chemical_classification, lcsh:QD241-441, Antioxidant, lcsh:Organic chemistry, Chemistry, medicine.medical_treatment, Organic Chemistry, Iodide, medicine, Organic chemistry
Abstract

Several routes to the title compounds were explored; a) from 4-ethoxy-quinaldine-1-oxide and methylmagnesium iodide; b) from 3,3-dimethylacrylic acid, 3-chloro-3-methylbutyric acid or 3amino-3-methylbutyric acid and appropriate anilines or activated fluorobenzenes and c) from 2,2-dimethyl-1,2,3,4-tetrahydroquinolines by Boc protection, BH3/H2O2 mediated 4hydroxylation and oxidation. The last process proved optimal, but nitroxides of the products were insufficiently stable to be isolated.

Published
2000

23. Pharmaceuticals, pharmacists and profits

Author

Melanie Frodsham and Phillip Clarke

Subjects
Service (business), business.industry, education, Pharmacy, Context (language use), Pharmaceutical Benefits Scheme, Public relations, Clinical pharmacy, Health care, Medicine, Pharmacology (medical), Medical prescription, Letters to the Editor, business, health care economics and organizations, Health policy
Abstract

Editor, – In his article, ‘Pharmaceuticals, pharmacists and profits: a health policy perspective’ (Aust Prescr 2014;37:148-9), Professor Philip Clarke highlights the importance of the price disclosure policy in reducing government spending on pharmaceuticals. However, Professor Clarke blatantly disregards the important role that community pharmacists play by comparing pharmacies to ‘firms that sell computers or mobile phones’. He asks why community pharmacy should have the support of taxpayer funds in order to remain viable while electronics stores do not. What a ridiculous comparison! Community pharmacies are staffed by highly trained health professionals and are essential in providing timely access to prescription medicines. This is an essential service that must remain a viable business for those involved. In addition to this, community pharmacists also provide a range of important services including counselling on the use of medicines, drug information and advice, primary health care, medication management services and delivery of medicines to the elderly and disabled. These services are generally provided free of charge and help to reduce medication-related hospital admissions which cost $1.2 billion annually. Australian pharmacists are well attuned to the need to ensure that the Pharmaceutical Benefits Scheme (PBS) remains sustainable, especially in the context of our ageing population. They are calling for increased opportunities to provide funded health care and medication management services. Pharmacists remain one of the most accessible health professionals with anyone being able to walk into a pharmacy (often open long hours) and obtain advice within 10 minutes. Community pharmacies are ideally placed to provide an expanded range of services where current gaps exist.

Published
2015

24. Substituted azaquinazolinones as modulators of GHSr-1a for the treatment of type II diabetes and obesity

Author

Susan Helen Davis, Gillian A. Bottomley, Chrystelle Marie Rasamison, Phillip Clarke, Eleanor Curtis, James Charles Bell, John Keily, Patrick Eric Hanrahan, Gary Moore, Stuart Bradley, Graham Dawson, Jason Bloxham, and James G. Horswill

Subjects
Male, medicine.medical_specialty, Clinical Biochemistry, hERG, Pharmaceutical Science, Administration, Oral, Biological Availability, Pharmacology, Biochemistry, Type ii diabetes, Rats, Sprague-Dawley, Structure-Activity Relationship, Internal medicine, Diabetes mellitus, Drug Discovery, medicine, Structure–activity relationship, Potency, Animals, Humans, Hypoglycemic Agents, Obesity, Receptor, Receptors, Ghrelin, Molecular Biology, Quinazolinones, Aza Compounds, biology, Chemistry, Organic Chemistry, medicine.disease, Ether-A-Go-Go Potassium Channels, Rats, Kinetics, Endocrinology, Diabetes Mellitus, Type 2, Drug Design, biology.protein, Molecular Medicine, Ghrelin, Hydrophobic and Hydrophilic Interactions
Abstract

Substituted azaquinazolinones were identified as antagonists of the GHSr-1A receptor for the treatment of type II diabetes and obesity. Optimisation for potency and LogD lead to the identification of orally bioavailable, potent antagonists with improved selectivity over hERG.

Published
2011

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