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1,864 results on '"Lonie, A"'

1. Knowledge-grounded Adaptation Strategy for Vision-language Models: Building Unique Case-set for Screening Mammograms for Residents Training

Author

Khan, Aisha Urooj, Garrett, John, Bradshaw, Tyler, Salkowski, Lonie, Jeong, Jiwoong Jason, Tariq, Amara, and Banerjee, Imon

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

A visual-language model (VLM) pre-trained on natural images and text pairs poses a significant barrier when applied to medical contexts due to domain shift. Yet, adapting or fine-tuning these VLMs for medical use presents considerable hurdles, including domain misalignment, limited access to extensive datasets, and high-class imbalances. Hence, there is a pressing need for strategies to effectively adapt these VLMs to the medical domain, as such adaptations would prove immensely valuable in healthcare applications. In this study, we propose a framework designed to adeptly tailor VLMs to the medical domain, employing selective sampling and hard-negative mining techniques for enhanced performance in retrieval tasks. We validate the efficacy of our proposed approach by implementing it across two distinct VLMs: the in-domain VLM (MedCLIP) and out-of-domain VLMs (ALBEF). We assess the performance of these models both in their original off-the-shelf state and after undergoing our proposed training strategies, using two extensive datasets containing mammograms and their corresponding reports. Our evaluation spans zero-shot, few-shot, and supervised scenarios. Through our approach, we observe a notable enhancement in Recall@K performance for the image-text retrieval task.

Published
2024

6. Prevalence of persistent SARS-CoV-2 in a large community surveillance study

Author

Ghafari, Mahan, Hall, Matthew, Golubchik, Tanya, Ayoubkhani, Daniel, House, Thomas, MacIntyre-Cockett, George, Fryer, Helen R., Thomson, Laura, Nurtay, Anel, Kemp, Steven A., Ferretti, Luca, Buck, David, Green, Angie, Trebes, Amy, Piazza, Paolo, Lonie, Lorne J., Studley, Ruth, Rourke, Emma, Smith, Darren L., Bashton, Matthew, Nelson, Andrew, Crown, Matthew, McCann, Clare, Young, Gregory R., Santos, Rui Andre Nunes dos, Richards, Zack, Tariq, Mohammad Adnan, Cahuantzi, Roberto, Barrett, Jeff, Fraser, Christophe, Bonsall, David, Walker, Ann Sarah, and Lythgoe, Katrina

Published
2024
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7. Spatial intra-tumour heterogeneity and treatment-induced genomic evolution in oesophageal adenocarcinoma: implications for prognosis and therapy

Author

Sandra Brosda, Lauren G. Aoude, Vanessa F. Bonazzi, Kalpana Patel, James M. Lonie, Clemence J. Belle, Felicity Newell, Lambros T. Koufariotis, Venkateswar Addala, Marjan M. Naeini, AGITG DOCTOR Investigators, John V. Pearson, Lutz Krause, Nicola Waddell, and Andrew P. Barbour

Subjects
Tumour evolution, Whole-genome sequencing, Treatment impact, Oesophageal adenocarcinoma, Genetics, Medicine, QH426-470
Abstract

Abstract Background Oesophageal adenocarcinoma (OAC) is a highly heterogeneous cancer with poor survival. Standard curative treatment is chemotherapy with or without radiotherapy followed by oesophagectomy. Genomic heterogeneity is a feature of OAC and has been linked to treatment resistance. Methods Whole-genome sequencing data from 59 treatment-naïve and 18 post-treatment samples from 29 OAC patients was analysed. Twenty-seven of these were enrolled in the DOCTOR trial, sponsored by the Australasian Gastro-Intestinal Trials Group. Two biopsies from each treatment-naïve tumour were assessed to define ‘shared’ (between both samples) and ‘private’ (present in one sample) mutations. Results Mutational signatures SBS2/13 (APOBEC) and SBS3 (BRCA) were almost exclusively detected in private mutation populations of treatment-naïve tumours. Patients presenting these signatures had significantly worse disease specific survival. Furthermore, mutational signatures associated with platinum-based chemotherapy treatment as well as high platinum enrichment scores were only detected in post-treatment samples. Additionally, clones with high putative neoantigen binding scores were detected in some treatment-naïve samples suggesting immunoediting of clones. Conclusions This study demonstrates the high intra-tumour heterogeneity in OAC, as well as indicators for treatment-induced changes during tumour evolution. Intra-tumour heterogeneity remains a problem for successful treatment strategies in OAC.

Published
2024
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13. Tumour microenvironment influences response to treatment in oesophageal adenocarcinoma

Author

Clemence J. Belle, James M. Lonie, Sandra Brosda, and Andrew P. Barbour

Subjects
oesophageal adenocarcinoma, tumour microenvironment, immune infiltrate, immunotherapy, treatment response, immune checkpoints, Immunologic diseases. Allergy, RC581-607
Abstract

The poor treatment response of oesophageal adenocarcinoma (OAC) leads to low survival rates. Its increasing incidence makes finding more effective treatment a priority. Recent treatment improvements can be attributed to the inclusion of the tumour microenvironment (TME) and immune infiltrates in treatment decisions. OAC TME is largely immunosuppressed and reflects treatment resistance as patients with inflamed TME have better outcomes. Priming the tumour with the appropriate neoadjuvant chemoradiotherapy treatment could lead to higher immune infiltrations and higher expression of immune checkpoints, such as PD-1/PDL-1, CTLA4 or emerging new targets: LAG-3, TIM-3, TIGIT or ICOS. Multiple trials support the addition of immune checkpoint inhibitors to the current standard of care. However, results vary, supporting the need for better response biomarkers based on TME composition. This review explores what is known about OAC TME, the clinical significance of the various cell populations infiltrating it and the emerging therapeutical combination with a focus on immune checkpoints inhibitors.

Published
2023
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14. Policing illegal drug and wildlife trades : the role of the police, legal online platforms, private organisations and individuals, and cybercriminal traders

Author

Sebagh, Lonie Marie, Lusthaus, Jonathan, and Varese, Federico

Subjects
Social sciences--Experiments, Criminology, Cyber Security
Abstract

This thesis explores the actors and activities involved in the policing of online illegal drug and wildlife trades on the Darknet and surface web. As the role of policing evolves due to advances in technology, the blurring of national boundaries, the increasing knowledge and skills of other actors, and the growing volume and value of these trades, more research is required about who and what is involved in this endeavour to increase its efficiency. Policing has been argued to take place in a network, where various actors come together to perform operations (Dupont, 2004). One of the most recent policing classifications is Button (2019)'s policing taxonomy which involves technological components. This thesis designs its own policing framework and tests the relevance of Button (2019)'s model in the context of online illegal drug and wildlife trades. Beyond the Police which possess powers of search and arrest to protect citizens, legal online platforms have created trading policies and are monitoring and punishing misconduct on their sites to preserve their legality and reputation. Organisations and individuals in the private sector, non-profits, and academia have been gathering, analysing, and sharing data and expertise to help Police investigations and inform the public. Cybercriminal traders have also taken advantage of others for their own financial gain and consequently decreased trust on Darknet markets, as well as unintentionally providing the Police with ways to disrupt their markets from the inside. This exploratory research used mixed social science methods to gather complimentary quantitative and qualitative insights. Semi-structured interviews were performed with 20 experts in Police agencies, legal platforms, for-profit and non-profit organisations, and academia. The content of 200 Police and private organisation reports, news articles, blog posts, and legal platforms' trading policies was analysed. A pilot laboratory experiment also tested the behaviour of 138 participants following trust-related policing interventions in a fictitious online marketplace. This thesis contributes to the fields of sociology and (cyber)criminology by designing a new cyber policing classification based on the policing of online illegal drug and wildlife trades and by formulating the first 'policing script' summarising the activities various policing actors perform in this context, when, with whom, and how they complement each other.

Published
2021

15. The oesophageal adenocarcinoma tumour immune microenvironment dictates outcomes with different modalities of neoadjuvant therapy – results from the AGITG DOCTOR trial and the cancer evolution biobank

Author

James M. Lonie, Sandra Brosda, Vanessa F. Bonazzi, Lauren G. Aoude, Kalpana Patel, Ian Brown, Sowmya Sharma, Guy Lampe, Venkateswar Addala, Lambros T. Koufariotis, Scott Wood, Nicola Waddell, Riccardo Dolcetti, and Andrew P. Barbour

Subjects
oesophageal adenocarcinoma, tumour microenvironment, neoadjuvant therapy, survival, treatment response, Immunologic diseases. Allergy, RC581-607
Abstract

A plateau in treatment effect can be seen for the current ‘one-size-fits-all’ approach to oesophageal adenocarcinoma (OAC) management using neoadjuvant chemoradiotherapy (nCRT) or chemotherapy (nCT). In OAC, the tumour microenvironment (TME) is largely immunosuppressed, however a subgroup of patients with an immune-inflamed TME exist and show improved outcomes. We aimed to understand the overall immune-based mechanisms underlying treatment responses and patient outcomes in OAC, and in relation to neoadjuvant therapy modality. This study included 107 patients; 68 patients were enrolled in the Australian Gastro-Intestinal Trials Group sponsored DOCTOR Trial, and 38 patients were included from the Cancer Evolution Biobank. Matched pre-treatment and post-treatment tumour biopsies were used to perform multi-modality analysis of the OAC TME including NanoString mRNA expression analysis, multiplex and single colour immunohistochemistry (IHC), and peripheral blood mononuclear cell analysis of tumour-antigen specific T cell responses. Patients with the best clinicopathological outcomes and survival had an immune-inflamed TME enriched with anti-tumour immune cells and pathways. Those with the worst survival showed a myeloid T regulatory cell enriched TME, with decreased CD8+ cell infiltration and increased pro-tumour immune cells. Multiplex IHC analysis identified that high intra-tumoural infiltration of CD8+ cells, and low infiltration with CD163+ cells was associated with improved survival. High tumour core CD8+ T cell infiltration, and a low tumour margin infiltration of CD163+ cells was also associated with improved survival. nCRT showed improved survival compared with nCT for patients with low CD8+, or high CD163+ cell infiltration. Poly-functional T cell responses were seen with tumour-antigen specific T cells. Overall, our study supports the development of personalised therapeutic approaches based on the immune microenvironment in OAC. Patients with an immune-inflamed TME show favourable outcomes regardless of treatment modality. However, in those with an immunosuppressed TME with CD163+ cell infiltration, treatment with nCRT can improve outcomes. Our findings support previous studies into the TME of OAC and with more research, immune based biomarker selection of treatment modality may lead in improved outcomes in this deadly disease.

Published
2023
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16. Correction: Viral burden is associated with age, vaccination, and viral variant in a population-representative study of SARS-CoV-2 that accounts for time-since-infection-related sampling bias.

Author

Helen R Fryer, Tanya Golubchik, Matthew Hall, Christophe Fraser, Robert Hinch, Luca Ferretti, Laura Thomson, Anel Nurtay, Lorenzo Pellis, Thomas House, George MacIntyre-Cockett, Amy Trebes, David Buck, Paolo Piazza, Angie Green, Lorne J Lonie, Darren Smith, Matthew Bashton, Matthew Crown, Andrew Nelson, Clare M McCann, Mohammed Adnan Tariq, Claire J Elstob, Rui Nunes Dos Santos, Zack Richards, Xin Xhang, Joseph Hawley, Mark R Lee, Priscilla Carrillo-Barragan, Isobel Chapman, Sarah Harthern-Flint, COVID-19 Genomics UK (COG-UK) consortium, David Bonsall, and Katrina A Lythgoe

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

[This corrects the article DOI: 10.1371/journal.ppat.1011461.].

Published
2023
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17. Viral burden is associated with age, vaccination, and viral variant in a population-representative study of SARS-CoV-2 that accounts for time-since-infection-related sampling bias.

Author

Helen R Fryer, Tanya Golubchik, Matthew Hall, Christophe Fraser, Robert Hinch, Luca Ferretti, Laura Thomson, Anel Nurtay, Lorenzo Pellis, Thomas House, George MacIntyre-Cockett, Amy Trebes, David Buck, Paolo Piazza, Angie Green, Lorne J Lonie, Darren Smith, Matthew Bashton, Matthew Crown, Andrew Nelson, Clare M McCann, Mohammed Adnan Tariq, Claire J Elstob, Rui Nunes Dos Santos, Zack Richards, Xin Xhang, Joseph Hawley, Mark R Lee, Priscilla Carrillo-Barragan, Isobel Chapman, Sarah Harthern-Flint, COVID-19 Genomics UK (COG-UK) consortium, David Bonsall, and Katrina A Lythgoe

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

In this study, we evaluated the impact of viral variant, in addition to other variables, on within-host viral burden, by analysing cycle threshold (Ct) values derived from nose and throat swabs, collected as part of the UK COVID-19 Infection Survey. Because viral burden distributions determined from community survey data can be biased due to the impact of variant epidemiology on the time-since-infection of samples, we developed a method to explicitly adjust observed Ct value distributions to account for the expected bias. By analysing the adjusted Ct values using partial least squares regression, we found that among unvaccinated individuals with no known prior exposure, viral burden was 44% lower among Alpha variant infections, compared to those with the predecessor strain, B.1.177. Vaccination reduced viral burden by 67%, and among vaccinated individuals, viral burden was 286% higher among Delta variant, compared to Alpha variant, infections. In addition, viral burden increased by 17% for every 10-year age increment of the infected individual. In summary, within-host viral burden increases with age, is reduced by vaccination, and is influenced by the interplay of vaccination status and viral variant.

Published
2023
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21. CloudLaunch: Discover and Deploy Cloud Applications

Author

Afgan, Enis, Lonie, Andrew, Taylor, James, and Goonasekera, Nuwan

Subjects
Computer Science - Distributed, Parallel, and Cluster Computing
Abstract

Cloud computing is a common platform for delivering software to end users. However, the process of making complex-to-deploy applications available across different cloud providers requires isolated and uncoordinated application-specific solutions, often locking-in developers to a particular cloud provider. Here, we present the CloudLaunch application as a uniform platform for discovering and deploying applications for different cloud providers. CloudLaunch allows arbitrary applications to be added to a catalog with each application having its own customizable user interface and control over the launch process, while preserving cloud-agnosticism so that authors can easily make their applications available on multiple clouds with minimal effort. It then provides a uniform interface for launching available applications by end users across different cloud providers. Architecture details are presented along with examples of different deployable applications that highlight architectural features.

Published
2018

22. Constructing custom-made radiotranscriptomic signatures of vascular inflammation from routine CT angiograms: a prospective outcomes validation study in COVID-19

Author

Ahern, David J, Ai, Zhichao, Ainsworth, Mark, Allan, Chris, Allcock, Alice, Angus, Brian, Ansari, M Azim, Arancibia-Cárcamo, Carolina, Aschenbrenner, Dominik, Attar, Moustafa, Baillie, J Kenneth, Barnes, Eleanor, Bashford-Rogers, Rachael, Bashyal, Archana, Beer, Sally, Berridge, Georgina, Beveridge, Amy, Bibi, Sagida, Bicanic, Tihana, Blackwell, Luke, Bowness, Paul, Brent, Andrew, Brown, Andrew, Broxholme, John, Buck, David, Burnham, Katie, Byrne, Helen, Camara, Susana, Ferreira, Ivan Candido, Charles, Philip, Chen, Wentao, Chen, Yi-Ling, Chong, Amanda, Clutterbuck, Elizabeth, Coles, Mark, Conlon, Christopher, Cornall, Richard, Cribbs, Adam, Curion, Fabiola, Davenport, Emma, Davidson, Neil, Davis, Simon, Dendrou, Calliope, Dequaire, Julie, Dib, Lea, Docker, James, Dold, Christina, Dong, Tao, Downes, Damien, Drakesmith, Hal, Dunachie, Susanna, Duncan, David, Eijsbouts, Chris, Esnouf, Robert, Espinosa, Alexis, Etherington, Rachel, Fairfax, Benjamin, Fairhead, Rory, Fang, Hai, Fassih, Shayan, Felle, Sally, Fernandez Mendoza, Maria, Ferreira, Ricardo, Fischer, Roman, Foord, Thomas, Forrow, Aden, Frater, John, Fries, Anastasia, Gallardo Sanchez, Veronica, Garner, Lucy, Geeves, Clementine, Georgiou, Dominique, Godfrey, Leila, Golubchik, Tanya, Gomez Vazquez, Maria, Green, Angie, Harper, Hong, Harrington, Heather, Heilig, Raphael, Hester, Svenja, Hill, Jennifer, Hinds, Charles, Hird, Clare, Ho, Ling-Pei, Hoekzema, Renee, Hollis, Benjamin, Hughes, Jim, Hutton, Paula, Jackson-Wood, Matthew, Jainarayanan, Ashwin, James-Bott, Anna, Jansen, Kathrin, Jeffery, Katie, Jones, Elizabeth, Jostins, Luke, Kerr, Georgina, Kim, David, Klenerman, Paul, Knight, Julian, Kumar, Vinod, Kumar Sharma, Piyush, Kurupati, Prathiba, Kwok, Andrew, Lee, Angela, Linder, Aline, Lockett, Teresa, Lonie, Lorne, Lopopolo, Maria, Lukoseviciute, Martyna, Luo, Jian, Marinou, Spyridoula, Marsden, Brian, Martinez, Jose, Matthews, Philippa, Mazurczyk, Michalina, McGowan, Simon, McKechnie, Stuart, Mead, Adam, Mentzer, Alexander, Mi, Yuxin, Monaco, Claudia, Montadon, Ruddy, Napolitani, Giorgio, Nassiri, Isar, Novak, Alex, O'Brien, Darragh, O'Connor, Daniel, O'Donnell, Denise, Ogg, Graham, Overend, Lauren, Park, Inhye, Pavord, Ian, Peng, Yanchun, Penkava, Frank, Pereira Pinho, Mariana, Perez, Elena, Pollard, Andrew, Powrie, Fiona, Psaila, Bethan, Quan, T Phuong, Repapi, Emmanouela, Revale, Santiago, Silva-Reyes, Laura, Richard, Jean-Baptiste, Rich-Griffin, Charlotte, Ritter, Thomas, Rollier, Christine, Rowland, Matthew, Ruehle, Fabian, Salio, Mariolina, Sansom, Stephen Nicholas, Sanches Peres, Raphael, Santos Delgado, Alberto, Sauka-Spengler, Tatjana, Schwessinger, Ron, Scozzafava, Giuseppe, Screaton, Gavin, Seigal, Anna, Semple, Malcolm, Sergeant, Martin, Simoglou Karali, Christina, Sims, David, Skelly, Donal, Slawinski, Hubert, Sobrinodiaz, Alberto, Sousos, Nikolaos, Stafford, Lizzie, Stockdale, Lisa, Strickland, Marie, Sumray, Otto, Sun, Bo, Taylor, Chelsea, Taylor, Stephen, Taylor, Adan, Thongjuea, Supat, Thraves, Hannah, Todd, John, Tomic, Adriana, Tong, Orion, Trebes, Amy, Trzupek, Dominik, Tucci, Felicia Anna, Turtle, Lance, Udalova, Irina, Uhlig, Holm, van Grinsven, Erinke, Vendrell, Iolanda, Verheul, Marije, Voda, Alexandru, Wang, Guanlin, Wang, Lihui, Wang, Dapeng, Watkinson, Peter, Watson, Robert, Weinberger, Michael, Whalley, Justin, Witty, Lorna, Wray, Katherine, Xue, Luzheng, Yuen Yeung, Hing, Yin, Zixi, Young, Rebecca, Youngs, Jonathan, Zhang, Ping, Zurke, Yasemin-Xiomara, Banning, Adrian, Antonopoulos, Alexios, Bajaj, Amrita, Kelion, Andrew, Deshpande, Aparna, Kardos, Attila, Hudson, Benjamin, Koo, Bon-Kwon, Shirodaria, Cheerag, Xie, Cheng, Kotanidis, Christos, Mahon, Ciara, Berry, Colin, Adlam, David, Newby, David, Connolly, Derek, Scaletta, Diane, Alexander, Donna, Nicol, Ed, McAlindon, Elisa, Oikonomou, Evangelos, Pugliese, Francesca, Pontone, Gianluca, Benedetti, Giulia, He, Guo-Wei, West, Henry, Kondo, Hidekazu, Benedek, Imre, Das, Intrajeet, Deanfield, John, Graby, John, Greenwood, John, Rodrigues, Jonathan, Ge, Junbo, Channon, Keith, Fabritz, Larissa, Fan, Li-Juan, Kingham, Lucy, Guglielmo, Marco, Lyasheva, Maria, Schmitt, Matthias, Beer, Meinrad, Anderson, Michelle, Desai, Milind, Marwan, Mohamed, Takahashi, Naohiko, Mehta, Nehal, Dai, Neng, Screaton, Nicholas, Sabharwal, Nikant, Maurovich-Horvat, Pál, Rao, Praveen, Kotronias, Rafail, Kharbanda, Rajesh, Preston, Rebecca, Wood, Richard, Blankstein, Ron, Rajani, Ronak, Mirsadraee, Saeed, Munir, Shahzad, Thomas, Sheena, Neubauer, Stefan, Klömpken, Steffen, Petersen, Steffen, Achenbach, Stephan, Anthony, Susan, Mak, Sze, Mittal, Tarun, Benedek, Theodora, Sharma, Vinoda, Lin, Wen-Hua, Kotanidis, Christos P, Rodrigues, Jonathan C L, O’Connor, Daniel, Siddique, Muhammad, Lockstone, Helen, Oikonomou, Evangelos K, Badi, Ileana, Lumley, Sheila F, Constantinides, Bede, Sanderson, Nicholas, Rodger, Gillian, Chau, Kevin K, Lodge, Archie, Tsakok, Maria, Gleeson, Fergus, Indrajeet, Das, Hudson, Benjamin J, Srivastava, Vivek, Farid, Shakil, Krasopoulos, George, Sayeed, Rana, Newby, David E, Channon, Keith M, and Antoniades, Charalambos

Published
2022
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24. The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2022 update.

Author

Enis Afgan, Anton Nekrutenko, Björn A. Grüning, Daniel J. Blankenberg, Jeremy Goecks, Michael C. Schatz, Alexander E. Ostrovsky, Alexandru Mahmoud, Andrew J. Lonie, Anna Syme, Anne Fouilloux, Anthony Bretaudeau, Anup Kumar, Arthur C. Eschenlauer, Assunta D. Desanto, Aysam Guerler, Beatriz Serrano-Solano, Bérénice Batut, Bradley W. Langhorst, Bridget Carr, Bryan A. Raubenolt, Cameron J. Hyde, Catherine J. Bromhead, Christopher B. Barnett, Coline Royaux, Cristóbal Gallardo, Daniel J. Fornika, Dannon Baker, Dave Bouvier, Dave Clements, David A. de Lima Morais, David Lopez Tabernero, Delphine Larivière, Engy Nasr, Federico Zambelli, Florian Heyl, Fotis E. Psomopoulos, Frederik Coppens, Gareth R. Price, Gianmauro Cuccuru, Gildas Le Corguillé, Gregory Von Kuster, Gulsum Gudukbay, Helena Rasche, Hans-Rudolf Hotz, Ignacio Eguinoa, Igor V. Makunin, Isuru Ranawaka, James Taylor 0001, Jayadev Joshi, Jennifer Hillman-Jackson, John Chilton, Kaivan Kamali, Keith Suderman, Krzysztof Poterlowicz, Yvan Le Bras, Lucille Lopez-Delisle, Luke Sargent, Madeline E. Bassetti, Marco Antonio Tangaro, Marius van den Beek, Martin Cech, Matthias Bernt, Matthias Fahrner, Mehmet Tekman, Melanie Christine Föll, Michael R. Crusoe, Miguel Roncoroni, Natalie Kucher, Nate Coraor, Nicholas Stoler, Nick Rhodes, Nicola Soranzo, Niko Pinter, Nuwan Goonasekera, Pablo A. Moreno, Pavankumar Videm, Petera Melanie, Pietro Mandreoli, Pratik D. Jagtap, Qiang Gu, Ralf J. M. Weber, Ross Lazarus, Ruben H. P. Vorderman, Saskia D. Hiltemann, Sergey Golitsynskiy, Shilpa Garg, Simon A. Bray, Simon L. Gladman, Simone Leo, Subina P. Mehta, Timothy J. Griffin, Vahid Jalili, Yves Vandenbrouck, Victor Wen, Vijay K. Nagampalli, Wendi A. Bacon, Willem L. De Koning, Wolfgang Maier 0003, and Peter J. Briggs

Published
2022
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27. The SENSEI Generic In Situ Interface:

Author

Ayachit, Utkarsh, Whitlock, Brad, Wolf, Matthew, Loring, Burlen, Geveci, Berk, Lonie, David, and Bethel, E. Wes

Subjects
in situ visualization and analysis, high performance computing
Abstract

The SENSEI generic in situ interface is an API that promotes code portability and reusability. From the simulation view, a developer can instrument their code with the SENSEI API and then make make use of any number of in situ infrastructures. From the method view, a developer can write an in situ method using the SENSEI API, then expect it to run in any number of in situ infrastructures, or be invoked directly from a simulation code, with little or no modification. This paper presents the design principles underlying the SENSEI generic interface, along with some simplified coding examples.

Published
2017

28. The CNS-penetrant soluble guanylate cyclase stimulator CYR119 attenuates markers of inflammation in the central nervous system

Author

Susana S. Correia, Guang Liu, Sarah Jacobson, Sylvie G. Bernier, Jenny V. Tobin, Chad D. Schwartzkopf, Emily Atwater, Elisabeth Lonie, Sam Rivers, Andrew Carvalho, Peter Germano, Kim Tang, Rajesh R. Iyengar, Mark G. Currie, John R. Hadcock, Christopher J. Winrow, and Juli E. Jones

Subjects
Soluble guanylate cyclase, sGC, cGMP, Nitric oxide, CREB, Microglia, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background Inflammation in the central nervous system (CNS) is observed in many neurological disorders. Nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO–sGC–cGMP) signaling plays an essential role in modulating neuroinflammation. CYR119 is a CNS-penetrant sGC stimulator that amplifies endogenous NO–sGC–cGMP signaling. We evaluated target engagement and the effects of CYR119 on markers of neuroinflammation in vitro in mouse microglial cells and in vivo in quinolinic acid (QA)-induced and high-fat diet-induced rodent neuroinflammation models. Methods Target engagement was verified in human embryonic kidney (HEK) cells, rat primary neurons, mouse SIM-A9 cells, and in rats by measuring changes in cGMP and downstream targets of sGC signaling [phosphorylated vasodilator-stimulated phosphoprotein (pVASP), phosphorylated cAMP-response element binding (pCREB)]. In SIM-A9 cells stimulated with lipopolysaccharides (LPS), markers of inflammation were measured when cells were treated with or without CYR119. In rats, microinjections of QA and vehicle were administered into the right and left hemispheres of striatum, respectively, and then rats were dosed daily with either CYR119 (10 mg/kg) or vehicle for 7 days. The activation of microglia [ionized calcium binding adaptor molecule 1 (Iba1)] and astrocytes [glial fibrillary acidic protein (GFAP)] was measured by immunohistochemistry. Diet-induced obese (DIO) mice were treated daily with CYR119 (10 mg/kg) for 6 weeks, after which inflammatory genetic markers were analyzed in the prefrontal cortex. Results In vitro, CYR119 synergized with exogenous NO to increase the production of cGMP in HEK cells and in primary rat neuronal cell cultures. In primary neurons, CYR119 stimulated sGC, resulting in accumulation of cGMP and phosphorylation of CREB, likely through the activation of protein kinase G (PKG). CYR119 attenuated LPS-induced elevation of interleukin 6 (IL-6) and tumor necrosis factor (TNF) in mouse microglial cells. Following oral dosing in rats, CYR119 crossed the blood–brain barrier (BBB) and stimulated an increase in cGMP levels in the cerebral spinal fluid (CSF). In addition, levels of proinflammatory markers associated with QA administration or high-fat diet feeding were lower in rodents treated with CYR119 than in those treated with vehicle. Conclusions These data suggest that sGC stimulation could provide neuroprotective effects by attenuating inflammatory responses in nonclinical models of neuroinflammation.

Published
2021
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31. Short and long-read genome sequencing methodologies for somatic variant detection; genomic analysis of a patient with diffuse large B-cell lymphoma

Author

Hannah E. Roberts, Maria Lopopolo, Alistair T. Pagnamenta, Eshita Sharma, Duncan Parkes, Lorne Lonie, Colin Freeman, Samantha J. L. Knight, Gerton Lunter, Helene Dreau, Helen Lockstone, Jenny C. Taylor, Anna Schuh, Rory Bowden, and David Buck

Subjects
Medicine, Science
Abstract

Abstract Recent advances in throughput and accuracy mean that the Oxford Nanopore Technologies PromethION platform is a now a viable solution for genome sequencing. Much of the validation of bioinformatic tools for this long-read data has focussed on calling germline variants (including structural variants). Somatic variants are outnumbered many-fold by germline variants and their detection is further complicated by the effects of tumour purity/subclonality. Here, we evaluate the extent to which Nanopore sequencing enables detection and analysis of somatic variation. We do this through sequencing tumour and germline genomes for a patient with diffuse B-cell lymphoma and comparing results with 150 bp short-read sequencing of the same samples. Calling germline single nucleotide variants (SNVs) from specific chromosomes of the long-read data achieved good specificity and sensitivity. However, results of somatic SNV calling highlight the need for the development of specialised joint calling algorithms. We find the comparative genome-wide performance of different tools varies significantly between structural variant types, and suggest long reads are especially advantageous for calling large somatic deletions and duplications. Finally, we highlight the utility of long reads for phasing clinically relevant variants, confirming that a somatic 1.6 Mb deletion and a p.(Arg249Met) mutation involving TP53 are oriented in trans.

Published
2021
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32. ACR Appropriateness Criteria® Imaging of Invasive Breast Cancer.

Author

McDonald, Elizabeth S., Scheel, John R., Lewin, Alana A., Weinstein, Susan P., Dodelzon, Katerina, Dogan, Basak E., Fitzpatrick, Amy, Kuzmiak, Cherie M., Newell, Mary S., Paulis, Lisa V., Pilewskie, Melissa, Salkowski, Lonie R., Silva, H. Colleen, Sharpe, Richard E., Specht, Jennifer M., Ulaner, Gary A., and Slanetz, Priscilla J.

Abstract

As the proportion of women diagnosed with invasive breast cancer increases, the role of imaging for staging and surveillance purposes should be determined based on evidence-based guidelines. It is important to understand the indications for extent of disease evaluation and staging, as unnecessary imaging can delay care and even result in adverse outcomes. In asymptomatic patients that received treatment for curative intent, there is no role for imaging to screen for distant recurrence. Routine surveillance with an annual 2-D mammogram and/or tomosynthesis is recommended to detect an in-breast recurrence or a new primary breast cancer in women with a history of breast cancer, and MRI is increasingly used as an additional screening tool in this population, especially in women with dense breasts. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation. [ABSTRACT FROM AUTHOR]

Published
2024
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38. Bilateral Thoracic Outlet Syndrome from Anomalous 8th Cervical Vertebrae Ribs

Author

Scott Ferris and Sarah Lonie

Subjects
thoracic outlet syndrome, eighth cervical vertebra, cervical rib, brachial plexus, Orthopedic surgery, RD701-811, Neurology. Diseases of the nervous system, RC346-429
Abstract

Thoracic outlet syndrome (TOS) is a group of diverse disorders resulting from compression of neurovascular structures as they pass from the lower neck to upper limb. Neurological symptoms, such as pain, weakness, or paraesthesia, are much more common than vascular symptoms such as pallor or venous congestion. Anatomical abnormalities can contribute to this condition. Thirty percent of patients with TOS can have a cervical rib, arising from the transverse process of the 7th cervical vertebra, compared with 1% of the general population. We report the first case in the literature of neurogenic TOS from a cervical rib arising from a supernumerary 8th cervical vertebra. This patient had immediate improvement in TOS symptoms following scalene muscle surgery and resection of cervical and first thoracic ribs.

Published
2022
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41. Metallization of Magnesium Polyhydrides Under Pressure

Author

Lonie, David C., Hooper, James, Altintas, Bahadir, and Zurek, Eva

Subjects
Condensed Matter - Materials Science
Abstract

Evolutionary structure searches are used to predict stable phases with unique stoichiometries in the hydrogen-rich region of the magnesium/hydrogen phase diagram under pressure. MgH$_4$, MgH$_{12}$ and MgH$_{16}$ are found to be thermodynamically stable with respect to decomposition into MgH$_2$ and H$_2$ near 100 GPa, and all lie on the convex hull by 200 GPa. MgH$_4$ contains two H$^-$ anions and one H$_2$ molecule per Mg$^{2+}$ cation, whereas the hydrogenic sublattices of MgH$_{12}$ and MgH$_{16}$ are composed solely of H$_2^{\delta -}$ molecules. The high-hydrogen content stoichiometries have a large density of states at the Fermi level, and the $T_c$ of MgH$_{12}$ at 140 GPa is calculated to be nearly three times greater than that of the classic hydride, MgH$_2$, at 180 GPa.

Published
2013
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50. Establishing a distributed national research infrastructure providing bioinformatics support to life science researchers in Australia.

Author

Maria Victoria Schneider, Philippa C. Griffin, Sonika Tyagi, Madison Flannery, Saravanan Dayalan, Simon Gladman, Nathan S. Watson-Haigh, Philipp E. Bayer, Michael A. Charleston, Ira Cooke, Rob Cook, Richard J. Edwards, David Edwards, Dominique Gorse, Malcolm J. McConville, David Powell, Marc R. Wilkins, and Andrew Lonie

Published
2019
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