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1. Regulatory CD4+ T cells redirected against pathogenic CD8+ T cells protect NOD mice from development of autoimmune diabetes

Author

Dimitri Kakabadse, Dawei Chen, Sigal Fishman, Hadas Weinstein-Marom, Joanne Davies, Li Wen, Gideon Gross, and F. Susan Wong

Subjects
NOD mice, type 1 diabetes, CD8 + T cells, CAR (chimeric antigen receptor) Treg cell therapy, antigen-specific regulatory T cells, Immunologic diseases. Allergy, RC581-607
Abstract

IntroductionIn this study, we report a novel therapeutic approach redirecting antigen-specific CD4+ T cells recognizing a hybrid insulin peptide (BDC2.5 T cell receptor (TCR) transgenic CD4+ T cells) to attract and suppress islet-specific CD8+ T cells T cells in the non-obese diabetic (NOD) mouse model, and prevent the development of autoimmune diabetes.MethodsPurified BDC2.5 CD4+ T cells were induced to differentiate into regulatory T cells (Tregs). The Tregs were then electroporated with mRNA encoding chimeric human β2 microglobulin (hβ2m) covalently linked to insulin B chain amino acids 15-23 (designated INS-eTreg) or islet-specific glucose-6-phosphatase related protein (IGRP) peptide 206-214 (designated IGRP-eTreg). Immunoregulatory functions of these engineered regulatory T cells (eTregs) were tested by in vitro assays and in vivo co-transfer experiments with β-cell-antigen-specific CD8+ T cells in NOD.Scid mice or by adoptive transfer into young, pre-diabetic NOD mice.ResultsThese eTregs were phenotyped by flow cytometry, and shown to have high expression of FoxP3, as well as other markers of Treg function, including IL-10. They suppressed polyclonal CD4+ T cells and antigen-specific CD8+ T cells (recognizing insulin or IGRP), decreasing proliferation and increasing exhaustion and regulatory markers in vitro. In vivo, eTregs reduced diabetes development in co-transfer experiments with pathogenic antigen-specific CD8+ T cells (INS-CD8+ or IGRP-CD8+ cells) into NOD.Scid mice. Finally, when the eTreg were injected into young NOD mice, they reduced insulitis and prevented spontaneous diabetes in the recipient mice.ConclusionOur results suggest a novel therapeutic strategy to protect NOD mice by targeting antigen-specific cytotoxic CD8+ T cells, using redirected antigen-specific CD4+ Treg cells, to suppress autoimmune diabetes. This may suggest an innovative therapy for protection of people at risk of development of type 1 diabetes. more...

Published
2024
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2. Novel engineered B lymphocytes targeting islet-specific T cells inhibit the development of type 1 diabetes in non-obese diabetic Scid mice

Author

Dawei Chen, Dimitri Kakabadse, Sigal Fishman, Hadas Weinstein-Marom, Joanne Davies, Joanne Boldison, Terri C. Thayer, Li Wen, Gideon Gross, and F. Susan Wong

Subjects
type 1 diabetes, NOD mice, regulatory B cells, CD4+ T cells, CD8+ T cells, Immunologic diseases. Allergy, RC581-607
Abstract

IntroductionIn this study, we report a novel therapeutic approach using B lymphocytes to attract islet-specific T cells in the non-obese diabetic (NOD) mouse model and prevent the development of autoimmune diabetes. Rather than using the antibody receptor of B cells, this approach utilizes their properties as antigen-presenting cells to T cells.MethodsPurified splenic B cells were treated with lipopolysaccharide, which increases regulatory B (Breg) cell function, then electroporated with mRNA encoding either chimeric MHC-I or MHC-II molecules covalently linked to antigenic peptides. Immunoregulatory functions of these engineered B cells (e-B cells) were tested by in vitro assays and in vivo co-transfer experiments with beta-cell-antigen-specific CD8+ or CD4+ T cells in NOD.Scid mice, respectively.ResultsThe e-B cells expressing chimeric MHC-I-peptide inhibited antigen-specific CD8+ T-cell cytotoxicity in vitro. The e-B cells expressing chimeric MHC-II-peptide induced antigen-specific CD4+ T cells to express the regulatory markers, PD-1, ICOS, CTLA-4, Lag3, and Nrp1. Furthermore, e-B cells encoding the chimeric MHC-I and MHC-II peptide constructs protected NOD.Scid mice from autoimmune diabetes induced by transfer of antigen-specific CD8+ and CD4+ T cells.DiscussionMHC–peptide chimeric e-B cells interacted with pathogenic T cells, and protected the host from autoimmune diabetes, in a mouse model. Thus, we have successfully expressed MHC–peptide constructs in B cells that selectively targeted antigen-specific cells, raising the possibility that this strategy could be used to endow different protective cell types to specifically regulate/remove pathogenic cells. more...

Published
2023
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3. One Hundred Priority Questions for the Development of Sustainable Food Systems in Sub-Saharan Africa

Author

Adam J. M. Devenish, Petra Schmitter, Nugun. P. Jellason, Nafeesa Esmail, Nur M. Abdi, Selase K. Adanu, Barbara Adolph, Maha Al-Zu’bi, Amali A. Amali, Jennie Barron, Abbie S. A. Chapman, Alexandre M. Chausson, Moses Chibesa, Joanne Davies, Emmanuel Dugan, Glory I. Edwards, Anthony Egeru, Tagel Gebrehiwot, Geoffrey H. Griffiths, Amleset Haile, Henry G. Hunga, Lizzy Igbine, Ousman M. Jarju, Francis Keya, Muhammad Khalifa, Wamba A. Ledoux, Lemlem T. Lejissa, Pius Loupa, Jonathan Lwanga, Everisto D. Mapedza, Robert Marchant, Tess McLoud, Patience Mukuyu, Labram M. Musah, Morton Mwanza, Jacob Mwitwa, Dora Neina, Tim Newbold, Samuel Njogo, Elizabeth J. Z. Robinson, Wales Singini, Bridget B. Umar, Frank Wesonga, Simon Willcock, Jingyi Yang, and Joseph A. Tobias more...

Subjects
agricultural development, agroecosystems, environmental impacts, horizon scan, food security, food systems, Agriculture
Abstract

Sub-Saharan Africa is facing an expected doubling of human population and tripling of food demand over the next quarter century, posing a range of severe environmental, political, and socio-economic challenges. In some cases, key Sustainable Development Goals (SDGs) are in direct conflict, raising difficult policy and funding decisions, particularly in relation to trade-offs between food production, social inequality, and ecosystem health. In this study, we used a horizon-scanning approach to identify 100 practical or research-focused questions that, if answered, would have the greatest positive impact on addressing these trade-offs and ensuring future productivity and resilience of food-production systems across sub-Saharan Africa. Through direct canvassing of opinions, we obtained 1339 questions from 331 experts based in 55 countries. We then used online voting and participatory workshops to produce a final list of 100 questions divided into 12 thematic sections spanning topics from gender inequality to technological adoption and climate change. Using data on the background of respondents, we show that perspectives and priorities can vary, but they are largely consistent across different professional and geographical contexts. We hope these questions provide a template for establishing new research directions and prioritising funding decisions in sub-Saharan Africa. more...

Published
2023
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5. Gene expression profiling in NOD mice reveals that B cells are highly educated by the pancreatic environment during autoimmune diabetes

Author

Joanne Boldison, Jessica R. Hopkinson, Joanne Davies, James A. Pearson, Pia Leete, Sarah Richardson, Noel G. Morgan, and F. Susan Wong

Subjects
Endocrinology, Diabetes and Metabolism, Internal Medicine
Abstract

Aims/hypothesis B cells play an important role in driving the development of type 1 diabetes; however, it remains unclear how they contribute to local beta cell destruction during disease progression. Here, we use gene expression profiling of B cell subsets identified in inflamed pancreatic tissue to explore their primary functional role during the progression of autoimmune diabetes. Methods Transcriptional profiling was performed on FACS-sorted B cell subsets isolated from pancreatic islets and the pancreatic lymph nodes of NOD mice. Results B cells are highly modified by the inflamed pancreatic tissue and can be distinguished by their transcriptional profile from those in the lymph nodes. We identified both a discrete and a core shared gene expression profile in islet CD19+CD138– and CD19+CD138+ B cell subsets, the latter of which is known to have enriched autoreactivity during diabetes development. On localisation to pancreatic islets, compared with CD138– B cells, CD138+ B cells overexpress genes associated with adhesion molecules and growth factors. Their shared signature consists of gene expression changes related to the differentiation of antibody-secreting cells and gene regulatory networks associated with IFN signalling pathways, proinflammatory cytokines and Toll-like receptor (TLR) activation. Finally, abundant TLR7 expression was detected in islet B cells and was enhanced specifically in CD138+ B cells. Conclusions/interpretation Our study provides a detailed transcriptional analysis of islet B cells. Specific gene signatures and interaction networks have been identified that point towards a functional role for B cells in driving autoimmune diabetes. Graphical abstract more...

Published
2022
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6. Empagliflozin in Patients with Chronic Kidney Disease

Author

Herrington, William G, Staplin, Natalie, Wanner, Christoph, Green, Jennifer B, Hauske, Sibylle J, Emberson, Jonathan R, Preiss, David, Judge, Parminder, Mayne, Kaitlin J, Ng, Sarah Y A, Sammons, Emily, Zhu, Doreen, Hill, Michael, Stevens, Will, Wallendszus, Karl, Brenner, Susanne, Cheung, Alfred K, Liu, Zhi-Hong, Li, Jing, Hooi, Lai Seong, Liu, Wen, Kadowaki, Takashi, Nangaku, Masaomi, Levin, Adeera, Cherney, David, Maggioni, Aldo P, Pontremoli, Roberto, Deo, Rajat, Goto, Shinya, Rossello, Xavier, Tuttle, Katherine R, Steubl, Dominik, Petrini, Michaela, Massey, Dan, Eilbracht, Jens, Brueckmann, Martina, Landray, Martin J, Baigent, Colin, Haynes, Richard, The EMPA-KIDNEY Collaborative Group: Colin Baigent, Martin J Landray, Christoph Wanner, William G Herrington, Richard Haynes, Jennifer B Green, Sibylle J Hauske, Martina Brueckmann, Mark Hopley, Maximillian von-Eynatten, Jyothis George, Susanne Brenner, Alfred K Cheung, David Preiss, Zhi-Hong Liu, Jing Li, Laiseong Hooi, Wen Liu, Takashi Kadowaki, Masaomi Nangaku, Adeera Levin, David Cherney, Roberto Pontremoli, Aldo P Maggioni, Natalie Staplin, Jonathan Emberson, Stefan Hantel, Shinya Goto, Rajat Deo, Katherine R Tuttle, Michael Hill, Parminder Judge, Kaitlin J Mayne, Sarah Y A Ng, Xavier Rossello, Emily Sammons, Doreen Zhu, Peter Sandercock, Rudolf Bilous, Charles Herzog, Paul Whelton, Janet Wittes, Derrick Bennett, Patricia Achiri, Chrissie Ambrose, Cristina Badin, Jill Barton, Richard Brown, Andy Burke, Sebastian Butler, Rejive Dayanandan, Pia Donaldson, Robert Dykas, Lucy Fletcher, Kate Frederick, Hannah Kingston, Mo Gray, Emily Harding, Akiko Hashimoto, Lyn Howie, Susan Hurley, Ryonfa Lee, Nik Luker, Kevin Murphy, Mariko Nakahara, John Nolan, Michelle Nunn, Sorcha Mulligan, Akiko Omata, Sandra Pickworth, YanRu Qiao, Shraddha Shah, Karen Taylor, Alison Timadjer, Monique Willett, Liz Wincott, Qin Yan, Hui Yu, Louise Bowman, Fang Chen, Robert Clarke, Michelle Goonasekera, Waseem Karsan, Marion Mafham, Christina Reith, Mohammed Zayed, Ritva Ellison, Rowan Moys, Will Stevens, Kevin Verdel, Karl Wallendszus, Chris Bowler, Anna Brewer, Andy Measor, Guanguo Cui, Charles Daniels, Angela Field, Bob Goodenough, Ashley Lawson, Youcef Mostefai, Dheeptha Radhakrishnan, Samee Syed, Shuang Xia, Ruth Adewuyi-Dalton, Thomas Arnold, Anne-Marie Beneat, Anoushka Bhatt, Chloe Bird, Andrew Breach, Laura Brown, Mark Caple, Tatyana Chavagnon, Karen Chung, Sarah Clark, Luminita Condurache, Katarzyna Eichstadt, Marta Espino Obrero, Scarlett Forest, Helen French, Nick Goodwin, Andrew Gordon, Joanne Gordon, Cat Guest, Tina Harding, Michal Hozak, Matthew Lacey, David MacLean, Louise Messinger, Stewart Moffat, Martin Radley, Claire Shenton, Sarah Tipper, Jon Tyler, Lesley Weaving, James Wheeler, Elissa Williams, Tim Williams, Hamish Woodhouse, Angela Chamberlain, Jo Chambers, Joanne Davies, Denise Donaldson, Pati Faria-Shayler, Denise Fleming-Brown, Jennifer Ingell, Carol Knott, Anna Liew, Helen Lochhead, Juliette Meek, Isabel Rodriguez-Bachiller, Andrea Wilson, Patrick Zettergren, Rach AitSadi, Ian Barton, Alex Baxter, Yonghong Bu, Lukasz Danel, Sonja Grotjahn, Rijo Kurien, Michael Lay, Archie Maskill, Aleksandra Murawska, Rachel Raff, Allen Young, Rebecca Sardell, Vladimir Cejka, Marcela Fajardo-Moser, Christian Hartner, Doris Poehler, Janina Renner, Franziska Scheidemantel, Miya Bryant, Anita Hepditch, Cassandra Johnson, Erin Latore, Yolanda Miller, Lauren Price, Merilee Whalen, Ashleigh Wheeler, Jenny Ingell, Yu An, Yinghua Chen, Peiling Chen, Hao Dai, Hong Du, Fang Feng, Qing Guo, Libo Hou, Wuhanbilige Hundei, Binbin Jin, Yan Li, Jiamin Liu, Xia Song, Yanping Wang, Yanwu Yu, Ning Zhang, Lingshan Zhao, Hui Zhong, Cheng Beng Goh, Ye Mun Low, Soon Yi Sor, Farah Hanis Zulkipli, Sarojini Sivanandam, Natsuki Arai, Ai Fukasawa, Mizue Furukawa, Keisuke Habuki, Shoko Hayashi, Wakako Isari, Saki Kanegae, Maria Kawai, Reiki Kobayashi, Takako Kuramae, Chika Kuribayashi, Sawako Maeno, Satoshi Masumoto, Tomoko Morisaki, Minoru Oda, Kazue Sawada, Kenta Sugamori, Ayana Tatsuzawa, Aiko Tomita, Kazuyuki Yuasa, Hiroko Inazawa, Amanda Axler, Kerri Gallo, Ester Baldini, Barbara Bartolomei Mecatti, Francesca Bianchini, Martina Ceseri, Laura Cipressa, Gianna Fabbri, Andrea Lorimer, Donata Lucci, Sharang Ghavampour, Anja Knoppe, Hans Schmidt-Gurtler, Hubert Dumann, Sybille Merscher, Margret Patecki, Georg Rainer Schlieper, Anke Torp, Bianca Weber, Maja Zietz, Bernd Hohenstein, Urs Benck, Diliana Draganova, Thomas Weinreich, Lothar Wolf, Jasmine Gaidu, Hanna Reiner, Mandy Visnjic, Daniel Steffl, Marie Breitenfeldt, Annette Kraemer-Guth, Christine Braun, Simone Hagge, Michael Schomig, Stephan Matthias, Dominik Stoffler, Beate Schumacher, Thomas Sitter, Louise Fuessl, Julia Krappe, Jerome Loutan, Volker Vielhauer, Luciano Andriaccio, Magdalena Maurer, Bernhard Winkelmann, Martin Dursch, Linda Seifert, Linda Tenbusch, Julia Weinmann-Menke, Simone Boedecker, Wiebke Kaluza-Schilling, Daniel Kraus, Carina Krieger, Margit Schmude, Anne Schreiber, Ewelina Eckrich, Diethelm Tschope, Abdulwahab Arbi, Young Lee-Barkey, Bernd Stratmann, Natalie Prib, Sina Rolfsmeier, Irina Schneider, Lars Rump, Johannes Stegbauer, Christine Pötz, Mara Schemmelmann, Claudia Schmidt, Michael Koch, Sendogan Aker, Annika Küpper, Manuela Martin, Thiemo Pfab, Christian Albert, Michael Haase, Barbara Zander, Claudia Schneider-Danwitz, Wolfgang Seeger, Wolf-Adam Seeger, Britta Zemann, Christoph Stellbrink, Kristin Marx, Ekaterina Stellbrink, Britta Brettschneider, Stephanie Watson, Marion Iselt, Gerhard Klausmann, Inga-Nadine Kummer, Auguste Kutschat, Simone Streitenberger, Matthias Girndt, Silke Markau, Ina Girakossyan, Claudia Hanf, Joachim Beige, Ralph Wendt, Ulrike Schmidt, Andreas Schneider, Roland Veelken, Claudia Donhauser, Luis Becker, Nexhat Miftari, Ricarda Wolfling, Sarah Morlok, Christian Hugo, Alexander Paliege, Jens Passauer, Julian Stumpf, Annegret Fleischer, Kerstin Haaser, Bernhard Kraemer, Jan Jochims, Bernd Kruger, Claudia Foellinger, Anastassiya Reisler, Frank Strutz, Stefan Haack, Ursula Hohenstatt, Martin Busch, Konstantin Herfurth, Gunter Wolf, Rainer Paul, Hermann Haller, Jessica Kaufeld, Jan Menne, Elisabeth Bahlmann-Kroll, Angela Bergner, Horst Weihprecht, Aydin Er, Florian Sonntag, Elif Turan, Michael Wittmann, Franziska Klauser, Eva Voigt, Volker Schettler, Egbert Schulz, Madlen Rohnstock, Elke Schettler, Bernd Schroppel, Rene van Erp, Martin Kachele, Ulla Ludwig, Lena Schulte-Kemna, Waltraud Kmietschak, Elke Preiss, Martina Ruocco, Gunnar Heine, Martin Brzoska, Sebastian Gabel, Christina Büttner, Asma Sabarai, Bernhard Banas, Tobias Bergler, Yvonne Ehrl, Franz Putz, Antonia Schuster, Stefanie Kuhn, Torsten Schramm, Stefan Degenhardt, Gerhard Schmidt, Lea Weiland, Ulrike Giebeln-Hudnell, Jan Kielstein, Gabriele Eden, Brigitte Fuchs, Gina Morig, Manuela Winkler, Harald Darius, Charalampos Kriatselis, Carl-Philipp Roesch, Astrid Maselli, Dominik Alscher, Markus Ketteler, Moritz Schanz, Severin Schricker, Bianka Rettenmaier, Andrea Schwab, Pablo Pergola, Irene Leal, Melissa Cagle, Anna Romo, Anthony Torres, Sucharit Joshi, Kulli Barrett, Alexis Africano, Vicki Dodds, Dorleena Gowen, Ashlee Morris, Juan Fernandez, Guillermo Jimenez, Ricardo Viera, Kendaling Bruce, Ryan Barrios, Maylin Garcia, Kerelyn Garcia, Iradis Leal, David Tietjen, David Bains, Carlo Castillo, Genielle Brewer, Justin Davis, Natalie Freking, Brittany Golson, Sally Ham, Jesslyn Roesch, Pusadee Suchinda, Shameem Beigh, Usah Lilavivat, Joyce Bilton, Kim Bocchicchia, Jeffrey Turner, Neera Dahl, Aldo Peixoto, Yasemin Kavak, Lauren Liberti, Hari Nair, Nicolas Page, Stephanie Rosenberg, Kathryn Simmons, Tamara Isakova, Rebecca Frazier, Rupal Mehta, Anand Srivastava, Patrick Fox, Jonathan Hecktman, Alexander Hodakowski, Carlos Martinez, Rachel Phillips, Alexis Stevenson, Reem Mustafa, Kyle Jansson, Cassandra Kimber, Jason Stubbs, Ahmad Tuffaha, Sri Yarlagadda, Debbie Griffin, Elisabeth Laundy, Zhuo Tang, Radica Alicic, Ann Cooper, Lisa Davis, Ashwini Gore, Rebecca Goldfaden, Leslie Harvill, Lisa Hichkad, Barry Johns, Thomas Jones, Kayla Merritt, Jennifer Sheldon, Jennifer Stanfield, Lindsay Alexander, Kaitlyn Preston, Lindsey Wood, Rajesh Pradhan, Roger DeRaad, Kelli McIntosh, Louis Raymond, Michael Shepperd, Susan McLaughlin, Mary Seifert, Andrew Shepherd, Joseph Aiello, William Durham, Laurie Loudermilk, John Manley, Sabrina Burnette, Stephanie Evans, Tara Johnson, Lance Sloan, Judy Ann Acosta, Stacy Gillham, Katia Sloan, SueAnn Squyres, Michael Rocco, Amret Hawfield, Ben Bagwell, Lauren Richmond, Joseph Soufer, Subha Clarke, Amanda Aliu, Kristine Calabrese, Amanda Davis, Veronica Poma, Tracy Spinola, James Magee, Ricardo Silva, Rushab Choksi, Lorraine Dajani, John Evans, Anil George, Prasanth Krish, Gerard Martins, Mae Sheikh-Ali, David Sutton, Freda Driver, Abraham Hanburry, Laura Hume, Amber Hurst, Matthew Taddeo, Marla Turner, Veronica Yousif, Srinivasan Beddhu, Laith Al-Rabadi, Nikita Abraham, Amalia Caamano, Judy Carle, Victoria Gonce, Kaitlyn Staylor, Na Zhou, Shweta Bansal, Manoj Bhattarai, Kumar Sharma, Subrata Debnath, Aliseiya Garza, Chakradhar Velagapudi, Sergio Rovner, Javier Almeida, Pablo Casares, Verlaine Stewart-Ray, Rene Almaraz, Renata Dayrell, Ana Moncada, Ricardo Pulido, Roxana Rodriquez, Wasim Deeb, Kathryn DeGoursey, Rodel Gloria, Trevor Greene, Robert Miller, Edward Pereira, Miguel Roura, Debbie Domingo, Sasha Dorestin, William Hodge, Cathy Jackson, Deborah Lund, Katrina Taylor, Kenneth Boren, Brittany Cleveland, Sandra Gaiser, Mandeep Sahani, Logan Aldrich, Exodus Edmerson, Edmond Limon, Cole Valletta, Patricia Vasquez, Christopher Provenzano, Navkiranjot Brar, Heather Henderson, Bellovich Keith, Qur Khai, Quresh Khairullah, Gail Makos, Joel Topf, Sherry Gasko, Rosemarie Henschel, Kaitlin Knapp, Teresa Kozlowski, Paula LaFleur, Ashwathy Varughese, Hui Xue, Patricia Wu, Olga Arechiga, Shan Darbeau, Michael Fechter, Stephanie Martinez, Lenita Hanson, Nyla Cooper, Arelis Madera, Jay Cadorna, Rita Sheridan, Helen Sparks, Bradley Eilerman, Susanne Bodine, Wael Eid, Rebecca Flora, Amber Avery, Cashmere Hardy, Mihaela Biscoveanu, Steven Nagelberg, Tracey Cummins, Frederic Rahbari-Oskoui, Anju Oommen, Zohreh Forghani, Stacie Hitchcock, Darya Hosein, Diane Watkins, Minesh Patel, Anthony Lambert, Elizabeth Newman, Autumn Wood, Tammy Ross, Stephany Topping, Jeffrey Mulhern, Lorna Murphy, Ann Vasseur, Gregory Greenwood, Alexander Hadley, Denise Laurienti, Christopher Marshall, Nicholas McLean, Scott Satko, Brandy Caudill, Jacob Maris, Janice Rogers, Cindy Vanhoy, George Thomas, Georges Nakhoul, John O'Toole, Jonathan Taliercio, Leslie Cooperman, Marina Markovic, Barbara Tucky, Devasmita Dev, Alia Hasan, Hima Yalamanchili, Namita Jain, Lesley McNeil, Eric Wines, Jean Park, Adline Ghazi, Mia Hamm, Tejas Patel, Amy Mottl, Emily Chang, Vimal Derebail, Emmie Cole, Anne Froment, Sara Kelley, Jordan Osmond Foster, Vahid Mahabadi, Golriz Jafari, Anita Kamarzarian, Wendy Arriaga, Daisy Arteaga, Rosario Machicado, Genesis Naverrete, Prashant Kumar, Imran Nazeer, Karina Urquia, Tammi Glider, Vickie Jones, Savannah Rucker, Jennifer Wiley, Rahul Pandey, Jesus Arroyo, Harish Pariani, Mohammad Ahmad, Shahin Mozaffari, Erika Perez, Matthew Budoff, Sion Roy, Divya Birudaraju, Ahmed Ghanem, Sajad Hamal, Stephen Aronoff, Elisa Joye Petr, Richard Sachson, Jaime Wiebel, Sana Akram, Laurie Jones, Curtis Knight, Maurie Tarlac, Shahbaz Ahmed, Harold Szerlip, Akinwande Akinfolarin, Ankit Mehta, Shana Camp, Cindy Castro, Zanaida Cooper, Jessica Terry, Ahmed Awad, Bhavya Kothapalli, Ryan Lustig, Serine Alfaress, Hyder Jasim, Mary Parrigon, Dennis Karounos, Sadiq Ahmed, Maggie Berry, Ruth Oremus, Carlos Hernandez-Cassis, Elias Ugwu, Nazia Junejo, Nancy Suazo, Mark Segal, Amir Kazory, Sherry Brown, Tristan Daniels, Sofia Dayi, Renee Hogan, Kathy McCray, Jennifer Stickley, Mahboob Rahman, Mirela Dobre, Lavinia Negrea, Aparna Padiyar, Nishigandha Pradhan, Arash Rashidi, Nagaraju Sarabu, Vicki Donley, Tricia Young, Godson Oguchi, Judepatricks Onyema, Kahla Damianik, Jack Dienes, Judith Plummer-Morgan, Marilyn Roman, Mauver Skipper, Stacey-Ann Villaruel, Krystle Williams, Danny Sugimoto, Jeffrey Dugas, Ismeal Ahmed, Jamie Bhairoo, Dolores Rijos, Huzaifa Salim, Madita Gavrila, Kathryn Lafferty, Ria Rabara, Sally Ruse, Maria Weetman, James Bushnell, Albert Power, Alison Jenkins, Stefanie Jones, Amanda Scott, Cath Byrne, Mark Jesky, Alison Cowley, Emma McHaffie, Holly Waterfall, Jo Taylor, Laura Bough, Thomas Phillips, Barbara Winter-Goodwin, Sui Phin Kon, Iain MacDougall, Eirini Lioudaki, Sapna Shah, Claire Sharpe, Francisco Aguilar, Abegail Hernandez Pena, Conception Pugay, Amelia Te, Hugh Finn, Wasim Hanif, Samiul Mostafa, Alice Aitken, Katharine Draxlbauer, Evelina Grobovaite, Jennifer Kearney, Theresa McCarthy, Giorgio Gentile, Duncan Browne, Palanichamy Chellamuthu, Tabinda Dugal, Terri Chant, Laura Jones, Emily Laity, Megan Miners, James Muir, Elizabeth Swanson, Andrew Frankel, James Tomlinson, Marlon Alegata, Rashid Almasarwah, Anthoula Apostolidi, Maria Vourvou, Thomas Walters, Maarten Taal, Hari Dukka, Nitin Kolhe, Carly McDonald, Kelly White, Shiva Ugni, Smita Gunda, Rotimi Oluyombo, Vicki Brindle, Ping Coutts, Tracy Fuller, Evelyn Nadar, Suresh Ramadoss, Nichola Motherwell, Susannah Pajak, Louise Tonks, Sunil Bhandari, Richard Bodington, Adil Hazara, Dominic Fellowes, Christopher Wong, Christopher Goldsmith, Sherald Barnes, Ann Bennett, Claire Burston, Samantha Hope, Nicola Hunt, Lini Kurian, Richard Fish, Daniela Farrugia, Judy Lee, Emma Sadler, Hannah Turner, Christopher Hill, Henry Brown, Agnes Masengu, Peter Maxwell, Nina Bleakley, Hugh Murtagh, William Petchey, Vivian Yiu, Joanne Kellett, Angharad Williams, Helen Clarke, Victoria Carnall, Sarah Benyon, Caroline Blake, Stephanie Estcourt, Jane Piper, Neal Morgan, Carolyn Hutchinson, Teresa McKinley, Alastair Woodman, Judi Graham, Niall Leonard, John Smyth, Vicki Adell, Samantha Hagan, Ben Caplin, Amin Oomatia, Eleanor Damian, Toluleyi Sobande, Tim Doulton, Michael Delaney, Mahmoud Montasser, Jenny Hansen, David Loader, Angela Moon, Frances Morris, Smeeta Sinha, Chukwuma Chukwu, Amy Hudson, Diane Campbell, Melanie Kershaw, Stephanie Whittaker, Ayesha Irtiza-Ali, Farid Ghalli, Heba Nosseir, Allison Leslie, Kate Trivedi, Donald Fraser, Mohammad Alhadj Ali, Sian Griffin, Farah Latif, Justyna Witczak, Alexa Wonnacott, Lynda Jeffers, Yvette Webley, Paul Phelan, Eve Miller-Hodges, Ailsa Geddes, Margaret Glenwright, Amy Hunter, Thomas Pickett, Jim Moriarty, Linda Hill, Amanda Tyler, Waqar Ayub, Gail Evans, Sue Hewins, Davina Hewitt, Kerry Read, Samira Bell, Leanne Cosgrove, Rachel Craik, Shona Murray, Nitin Bhandary, Holly Coles, Rashmi Easow, Maya Joseph, Arif Khwaja, Yvonne Jackson, Angeline Mbuyisa, Rachel Sellars, Nihil Chitalia, Cynthia Mohandas, Anca Gherman, Charlotte Kamundi, Olumide Olufuwa, Kieran McCafferty, Adedolapo Adeleke, Cara Healy, Damini Jeyarajah, Edward Kinsella-Perks, Richard Smith, Brian Camilleri, Carol Buckman, Jenny Finch, Vanessa Rivers, Andrew Connor, Sheila Carr, Lisa Shainberg, Andrew Lewington, Richard Baker, Suzannah Dorey, Kay Tobin, Rosalyn Wheatley, Debasish Banerjee, Richard Hull, Sharirose Abat, Riny Paul, Mahzuz Karim, Zay Htet, Saad Tufail, Ravi Varma, Karen Convery, Deirdre Fottrell-Gould, Lisa Hudig, Emily Tropman, Thahir Abdul-Samad, Anne Grace, Marie Phipps, Rebecca Suckling, Subash Somalanka, Bhrigu Sood, Pauline Swift, Sarah Acheampong, Kwame Ansu, Martia Augustin, Anna Sampson, Lynn Vinall, Kim Wren, Shamila Wanninayake, Nicholas Wooding, Heather Edwards, Lydia Owen, Stephanie Bolton, Marion Carson, Michael Matthews, Nigel Brunskill, Jorge Jesus-Silva, Alex Howson, Mary Quashie-Akponeware, Hilary Tindall, Chidambaram Nethaji, Helen Eldon, Rajan Patel, Patrick Mark, Alastair Rankin, Michael Sullivan, Kirsty Forsyth, Rowan McDougall, Tanaji Dasgupta, Louisa Davies, Maggie Ryder, Philip Grimmer, Clare Macdonald, Mary Webster, Newcastle Newcastle, Timothy Ellam, Edwin Wong, Christine Meshykhi, Andrea Webster, Peter Wilson, Enric Vilar, Jocelyn Berdeprado, Eunice Doctolero, Lily Wilkinson, Frank McCarroll, Hesham Ammar, Ying Kuan, Conor Moran, Girish Shivashankar, Ryan Campbell, Deborah Glowski, Paula McDermott, Amar Ali, Zuber Patel, Christine Bond, Gillian Whalley, Haitao Zhang, Liu Yang, Lihua Zhang, Tingting Kan, Ling Zhu, Jinghong Zhao, Weiping Hou, Jing Wu, Hong Cheng, Weijing Bian, Zhirui Zhao, Fengmin Shao, Huixia Cao, Xiaojing Jiao, Peiyuan Niu, Jianying Niu, Yu Chen, Lihong Zhang, Shenglang Zhu, Haiyan Lin, Shaopeng Yao, Jiehui Chen, Ying Jiang, Ying Hu, Huaying Xiao, Fuye Yang, Xinzhou Zhang, Baochun Guo, Qiu Jin, Lixia Liu, Xiangcheng Xiao, Yanyun Xie, Ting Meng, Chuanwen Xu, Jie Huang, Yanmei Xu, Weixin Kong, Xiaoliang Wang, Qianpan Liu, Xueying Wang, Ming Gao, Xiumei Hu, Ying Lu, Li Wang, Kun Peng, Wei Wang, Qiuhong Gong, Jianfang Cai, Xiaojue Li, Xuejiao Liu, Shuhan Zhou, Hong Liu, Yao Weng, Shuai Tang, Yao Yao, Shi Zhao, Chen Cheng, Wei Wei, Na Li, Sadanah Aqashiah Mazlan, Alia Zubaidah Bahtar, Elliyyin Katiman, Noraini Othman, Lily Mushahar, Nurdiana Mazlan, Nur Sharafina Safiee, Sarasa Ramasamy, Hin Seng Wong, Hajar Ahmad Rosdi, Esther Zhao Zhi Tan, Ju Fan Tay, Kok Seng Teng, Hasnah Yahaya, Wen Jiun Liu, Lik Wee Ee, Kenneth Kay Leong Khoo, Yuana Mohd Yusoff, Fariz Safhan Mohamad Nor, Mohd Kamil Ahmad, Mohd Ramli Seman, Clare Hui Hong Tan, Laura Lui Sian Ngu, Jaime Yoke May Chan, Javelin Peji, Chek Loong Loh, Yee Yan Lee, Sridhar Ramanaidu, Kah Mean Thong, Yik Hong Wong, Suria Junus, Chen Hua Ching, Mohammad Faisal Asmee, Ku Ruziana Ku Md Razi, Chun Leong Low, Christopher Sze Bing Sim, Zhang Duan Tham, Noor Kamila Abdullah, Tai Meng Chen, Yong Chieh Chan, Eason Chang, Huan Yean Kang, Kai Quan Lee, Sue Ann Lee, Aik Kheng Lee, Jeevika Vinathan, Rizna Abdul 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Matthew, Turner, Marla, Yousif, Veronica, Beddhu, Srinivasan, Al-Rabadi, Laith, Abraham, Nikita, Caamano, Amalia, Carle, Judy, Gonce, Victoria, Staylor, Kaitlyn, Zhou, Na, Bansal, Shweta, Bhattarai, Manoj, Sharma, Kumar, Debnath, Subrata, Garza, Aliseiya, Velagapudi, Chakradhar, Rovner, Sergio, Almeida, Javier, Casares, Pablo, Stewart-Ray, Verlaine, Almaraz, Rene, Dayrell, Renata, Moncada, Ana, Pulido, Ricardo, Rodriquez, Roxana, Deeb, Wasim, Degoursey, Kathryn, Gloria, Rodel, Greene, Trevor, Miller, Robert, Pereira, Edward, Roura, Miguel, Domingo, Debbie, Dorestin, Sasha, Hodge, William, Jackson, Cathy, Lund, Deborah, Taylor, Katrina, Boren, Kenneth, Cleveland, Brittany, Gaiser, Sandra, Sahani, Mandeep, Aldrich, Logan, Edmerson, Exodu, Limon, Edmond, Valletta, Cole, Vasquez, Patricia, Provenzano, Christopher, Brar, Navkiranjot, Henderson, Heather, Keith, Bellovich, Khai, Qur, Khairullah, Quresh, Makos, Gail, Topf, Joel, Gasko, Sherry, Henschel, Rosemarie, Knapp, Kaitlin, Kozlowski, Teresa, Lafleur, Paula, Varughese, Ashwathy, Xue, Hui, Wu, Patricia, Arechiga, Olga, Darbeau, Shan, Fechter, Michael, Martinez, Stephanie, Hanson, Lenita, Cooper, Nyla, Madera, Areli, Cadorna, Jay, Sheridan, Rita, Sparks, Helen, Eilerman, Bradley, Bodine, Susanne, Eid, Wael, Flora, Rebecca, Avery, Amber, Hardy, Cashmere, Biscoveanu, Mihaela, Nagelberg, Steven, Cummins, Tracey, Rahbari-Oskoui, Frederic, Oommen, Anju, Forghani, Zohreh, Hitchcock, Stacie, Hosein, Darya, Watkins, Diane, Patel, Minesh, Lambert, Anthony, Newman, Elizabeth, Wood, Autumn, Ross, Tammy, Topping, Stephany, Mulhern, Jeffrey, Murphy, Lorna, Vasseur, Ann, Greenwood, Gregory, Hadley, Alexander, Laurienti, Denise, Marshall, Christopher, Mclean, Nichola, Satko, Scott, Caudill, Brandy, Maris, Jacob, Rogers, Janice, Vanhoy, Cindy, Thomas, George, Nakhoul, George, O'Toole, John, Taliercio, Jonathan, Cooperman, Leslie, Markovic, Marina, Tucky, Barbara, Dev, Devasmita, Hasan, Alia, Yalamanchili, Hima, Jain, Namita, Mcneil, Lesley, Wines, Eric, Park, Jean, Ghazi, Adline, Hamm, Mia, Patel, Teja, Mottl, Amy, Chang, Emily, Derebail, Vimal, Cole, Emmie, Froment, Anne, Kelley, Sara, Osmond Foster, Jordan, Mahabadi, Vahid, Jafari, Golriz, Kamarzarian, Anita, Arriaga, Wendy, Arteaga, Daisy, Machicado, Rosario, Naverrete, Genesi, Kumar, Prashant, Nazeer, Imran, Urquia, Karina, Glider, Tammi, Jones, Vickie, Rucker, Savannah, Wiley, Jennifer, Pandey, Rahul, Arroyo, Jesu, Pariani, Harish, Ahmad, Mohammad, Mozaffari, Shahin, Perez, Erika, Budoff, Matthew, Roy, Sion, Birudaraju, Divya, Ghanem, Ahmed, Hamal, Sajad, Aronoff, Stephen, Joye Petr, Elisa, Sachson, Richard, Wiebel, Jaime, Akram, Sana, Jones, Laurie, Knight, Curti, Tarlac, Maurie, Ahmed, Shahbaz, Szerlip, Harold, Akinfolarin, Akinwande, Mehta, Ankit, Camp, Shana, Castro, Cindy, Cooper, Zanaida, Terry, Jessica, Awad, Ahmed, Kothapalli, Bhavya, Lustig, Ryan, Alfaress, Serine, Jasim, Hyder, Parrigon, Mary, Karounos, Denni, Ahmed, Sadiq, Berry, Maggie, Oremus, Ruth, Hernandez-Cassis, Carlo, Ugwu, Elia, Junejo, Nazia, Suazo, Nancy, Segal, Mark, Kazory, Amir, Brown, Sherry, Daniels, Tristan, Dayi, Sofia, Hogan, Renee, Mccray, Kathy, Stickley, Jennifer, Rahman, Mahboob, Dobre, Mirela, Negrea, Lavinia, Padiyar, Aparna, Pradhan, Nishigandha, Rashidi, Arash, Sarabu, Nagaraju, Donley, Vicki, Young, Tricia, Oguchi, Godson, Onyema, Judepatrick, Damianik, Kahla, Dienes, Jack, Plummer-Morgan, Judith, Roman, Marilyn, Skipper, Mauver, Villaruel, Stacey-Ann, Williams, Krystle, Sugimoto, Danny, Dugas, Jeffrey, Ahmed, Ismeal, Bhairoo, Jamie, Rijos, Dolore, Salim, Huzaifa, Gavrila, Madita, Lafferty, Kathryn, Rabara, Ria, Ruse, Sally, Weetman, Maria, Bushnell, Jame, Power, Albert, Jenkins, Alison, Jones, Stefanie, Scott, Amanda, Byrne, Cath, Jesky, Mark, Cowley, Alison, Mchaffie, Emma, Waterfall, Holly, Taylor, Jo, Bough, Laura, Phillips, Thoma, Winter-Goodwin, Barbara, Phin Kon, Sui, Macdougall, Iain, Lioudaki, Eirini, Shah, Sapna, Sharpe, Claire, Aguilar, Francisco, Hernandez Pena, Abegail, Pugay, Conception, Te, Amelia, Finn, Hugh, Hanif, Wasim, Mostafa, Samiul, Aitken, Alice, Draxlbauer, Katharine, Grobovaite, Evelina, Kearney, Jennifer, Mccarthy, Theresa, Gentile, Giorgio, Browne, Duncan, Chellamuthu, Palanichamy, Dugal, Tabinda, Chant, Terri, Jones, Laura, Laity, Emily, Miners, Megan, Muir, Jame, Swanson, Elizabeth, Frankel, Andrew, Tomlinson, Jame, Alegata, Marlon, Almasarwah, Rashid, Apostolidi, Anthoula, Vourvou, Maria, Walters, Thoma, Taal, Maarten, Dukka, Hari, Kolhe, Nitin, Mcdonald, Carly, White, Kelly, Ugni, Shiva, Gunda, Smita, Oluyombo, Rotimi, Brindle, Vicki, Coutts, Ping, Fuller, Tracy, Nadar, Evelyn, Ramadoss, Suresh, Motherwell, Nichola, Pajak, Susannah, Tonks, Louise, Bhandari, Sunil, Bodington, Richard, Hazara, Adil, Fellowes, Dominic, Wong, Christopher, Goldsmith, Christopher, Barnes, Sherald, Bennett, Ann, Burston, Claire, Hope, Samantha, Hunt, Nicola, Kurian, Lini, Fish, Richard, Farrugia, Daniela, Lee, Judy, Sadler, Emma, Turner, Hannah, Hill, Christopher, Brown, Henry, Masengu, Agne, Maxwell, Peter, Bleakley, Nina, Murtagh, Hugh, Petchey, William, Yiu, Vivian, Kellett, Joanne, Williams, Angharad, Clarke, Helen, Carnall, Victoria, Benyon, Sarah, Blake, Caroline, Estcourt, Stephanie, Piper, Jane, Morgan, Neal, Hutchinson, Carolyn, Mckinley, Teresa, Woodman, Alastair, Graham, Judi, Leonard, Niall, Smyth, John, Adell, Vicki, Hagan, Samantha, Caplin, Ben, Oomatia, Amin, Damian, Eleanor, Sobande, Toluleyi, Doulton, Tim, Delaney, Michael, Montasser, Mahmoud, Hansen, Jenny, Loader, David, Moon, Angela, Morris, France, Sinha, Smeeta, Chukwu, Chukwuma, Hudson, Amy, Campbell, Diane, Kershaw, Melanie, Whittaker, Stephanie, Irtiza-Ali, Ayesha, Ghalli, Farid, Nosseir, Heba, Leslie, Allison, Trivedi, Kate, Fraser, Donald, Alhadj Ali, Mohammad, Griffin, Sian, Latif, Farah, Witczak, Justyna, Wonnacott, Alexa, Jeffers, Lynda, Webley, Yvette, Phelan, Paul, Miller-Hodges, Eve, Geddes, Ailsa, Glenwright, Margaret, Hunter, Amy, Pickett, Thoma, Moriarty, Jim, Hill, Linda, Tyler, Amanda, Ayub, Waqar, Evans, Gail, Hewins, Sue, Hewitt, Davina, Read, Kerry, Bell, Samira, Cosgrove, Leanne, Craik, Rachel, Murray, Shona, Bhandary, Nitin, Coles, Holly, Easow, Rashmi, Joseph, Maya, Khwaja, Arif, Jackson, Yvonne, Mbuyisa, Angeline, Sellars, Rachel, Chitalia, Nihil, Mohandas, Cynthia, Gherman, Anca, Kamundi, Charlotte, Olufuwa, Olumide, Mccafferty, Kieran, Adeleke, Adedolapo, Healy, Cara, Jeyarajah, Damini, Kinsella-Perks, Edward, Smith, Richard, Camilleri, Brian, Buckman, Carol, Finch, Jenny, Rivers, Vanessa, Connor, Andrew, Carr, Sheila, Shainberg, Lisa, Lewington, Andrew, Baker, Richard, Dorey, Suzannah, Tobin, Kay, Wheatley, Rosalyn, Banerjee, Debasish, Hull, Richard, Abat, Sharirose, Paul, Riny, Karim, Mahzuz, Htet, Zay, Tufail, Saad, Varma, Ravi, Convery, Karen, Fottrell-Gould, Deirdre, Hudig, Lisa, Tropman, Emily, Abdul-Samad, Thahir, Grace, Anne, Phipps, Marie, Suckling, Rebecca, Somalanka, Subash, Sood, Bhrigu, Swift, Pauline, Acheampong, Sarah, Ansu, Kwame, Augustin, Martia, Sampson, Anna, Vinall, Lynn, Wren, Kim, Wanninayake, Shamila, Wooding, Nichola, Edwards, Heather, Owen, Lydia, Bolton, Stephanie, Carson, Marion, Matthews, Michael, Brunskill, Nigel, Jesus-Silva, Jorge, Howson, Alex, Quashie-Akponeware, Mary, Tindall, Hilary, Nethaji, Chidambaram, Eldon, Helen, Patel, Rajan, Mark, Patrick, Rankin, Alastair, Sullivan, Michael, Forsyth, Kirsty, Mcdougall, Rowan, Dasgupta, Tanaji, Davies, Louisa, Ryder, Maggie, Grimmer, Philip, Macdonald, Clare, Webster, Mary, Newcastle, Newcastle, Ellam, Timothy, Wong, Edwin, Meshykhi, Christine, Webster, Andrea, Wilson, Peter, Vilar, Enric, Berdeprado, Jocelyn, Doctolero, Eunice, Wilkinson, Lily, Mccarroll, Frank, Ammar, Hesham, Kuan, Ying, Moran, Conor, Shivashankar, Girish, Campbell, Ryan, Glowski, Deborah, Mcdermott, Paula, Ali, Amar, Patel, Zuber, Bond, Christine, Whalley, Gillian, Zhang, Haitao, Yang, Liu, Zhang, Lihua, Kan, Tingting, Zhu, Ling, Zhao, Jinghong, Hou, Weiping, Wu, Jing, Cheng, Hong, Bian, Weijing, Zhao, Zhirui, Shao, Fengmin, Cao, Huixia, Jiao, Xiaojing, Niu, Peiyuan, Niu, Jianying, Chen, Yu, Zhang, Lihong, Zhu, Shenglang, Lin, Haiyan, Yao, Shaopeng, Chen, Jiehui, Jiang, Ying, Hu, Ying, Xiao, Huaying, Yang, Fuye, Zhang, Xinzhou, Guo, Baochun, Jin, Qiu, Liu, Lixia, Xiao, Xiangcheng, Xie, Yanyun, Meng, Ting, Xu, Chuanwen, Huang, Jie, Xu, Yanmei, Kong, Weixin, Wang, Xiaoliang, Liu, Qianpan, Wang, Xueying, Gao, Ming, Hu, Xiumei, Lu, Ying, Wang, Li, Peng, Kun, Wang, Wei, Gong, Qiuhong, Cai, Jianfang, Li, Xiaojue, Liu, Xuejiao, Zhou, Shuhan, Liu, Hong, Weng, Yao, Tang, Shuai, Yao, Yao, Zhao, Shi, Cheng, Chen, Wei, Wei, Li, Na, Aqashiah Mazlan, Sadanah, Zubaidah Bahtar, Alia, Katiman, Elliyyin, Othman, Noraini, Mushahar, Lily, Mazlan, Nurdiana, Sharafina Safiee, Nur, Ramasamy, Sarasa, Seng Wong, Hin, Ahmad Rosdi, Hajar, Zhao Zhi Tan, Esther, Fan Tay, Ju, Seng Teng, Kok, Yahaya, Hasnah, Jiun Liu, Wen, Wee Ee, Lik, Kay Leong Khoo, Kenneth, Mohd Yusoff, Yuana, Safhan Mohamad Nor, Fariz, Kamil Ahmad, Mohd, Ramli Seman, Mohd, Hui Hong Tan, Clare, Lui Sian Ngu, Laura, Yoke May Chan, Jaime, Peji, Javelin, Loong Loh, Chek, Yan Lee, Yee, Ramanaidu, Sridhar, Mean Thong, Kah, Hong Wong, Yik, Junus, Suria, Hua Ching, Chen, Faisal Asmee, Mohammad, Ruziana Ku Md Razi, Ku, Leong Low, Chun, Sze Bing Sim, Christopher, Duan Tham, Zhang, Kamila Abdullah, Noor, Meng Chen, Tai, Chieh Chan, Yong, Chang, Eason, Yean Kang, Huan, Quan Lee, Kai, Ann Lee, Sue, Kheng Lee, Aik, Vinathan, Jeevika, Abdul Cader, Rizna, Mustafar, Ruslinda, Kamaruzaman, Lydia, Mohd, Rozita, Ismail, Rahimah, Men Leong, Chong, Koon Low, Chee, Wei Wong, Liang, Adnan, Norlezah, Ibrahim, Sabariah, Zaimi Abdul Wahab, Mohamad, Bavanandan, Sunita, Shen Lim, Yik, Hazlina Wan Mohamad, Wan, Munirah Jaafar, Siti, Ashykeen Mohd Fauzi, Nur, Sudin, Aziee, Kun Lim, Soo, Chung Gan, Chye, Hing, Albert, Ahmad Faizal Alaidin Razali, Wan, Fong Liew, Yew, Bao Tyng Chan, Chelsia, Chih Cheng, Mei, Chen Ong, Yu, Meng Ong, Loke, Amalina Mohamed Affandi, Farah, Rahmat, Korina, Chai Peng, Ban, Amat, Masayu, Hadafi Ahmad, Nuzaimin, Yee Mah, Doo, Loon Tye, Yi, Azhari, Zaid, Nabilah Mohamad Zaini, Siti, Aidil Musa, Mohd, Ahmad Miswan, Norazinizah, Ramli, Rafizanur, Aziah Ahmad, Nor, Leong Goh, Bak, Izah Ahmad, Nurul, Huda Ibrahim, Fairol, Jian Ng, Tze, Shanmuganathan, Malini, Lian Tay, Li, Harun, Zaiha, Ramli, Salmi, 'Ain Yusof, Nurul, Abd Rahman, Rossenizal, Iqbal Abdul Hafidz, Muhammad, Hidayati Mohd Sharif, Nur, Yasmoon Awang, Irda, Nakashima, Eitaro, Imamine, Rui, Minatoguchi, Makiko, Miura, Yukari, Nakaoka, Miduki, Suzuki, Yoshiki, Yoshikawa, Hitomi, Shin, Koki, Fujita, Kanae, Iwasa, Misuzu, Sasajima, Haruka, Sato, Airi, Hamamoto, Yoshiyuki, Fujita, Yuki, Haraguchi, Takuya, Hyo, Takanori, Izumi, Kiyohiro, Komiya, Toshiyuki, Kubota, Sodai, Kurose, Takeshi, Kuwata, Hitoshi, Nakatani, Susumu, Oishi, Kaori, Okamoto, Saki, Okamura, Kaori, Takeoka, Jun, Tanaka, Nagaaki, Tanigaki, Katsuya, Toda, Naohiro, Watanabe, Koin, Komori, Hiromi, Kumuji, Rika, Takesada, Asako, Tanaka, Aya, Maruyama, Shoichi, Hasegawa, Tomonori, Ishiguro, Akiko, Ishimoto, Takuji, Ito, Kazuhiro, Kamimura, Yutaka, Kato, Noritoshi, Kato, Sawako, Kojima, Hiroshi, Kosugi, Tomoki, Maeda, Kayaho, Mizuno, Masasi, Saito, Shoji, Sato, Hitomi, Sato, Yuka, Suzuki, Yasuhiro, Tanaka, Akihito, Yasuda, Yoshinari, Hasegawa, Fujiko, Hayashi, Maiko, Higashi, Shizuka, Shimamura, Kaho, Sumi, Momoko, Tajima, Kazuki, Unekawa, Chimaki, Wakayama, Kana, Wakita, Yukiko, Otani, Takatoshi, Imai, Ayako, Kawashima, Sayaka, Kogure, Eri, Sato, Tomoe, Takezawa, Misato, Yoshida, Shinya, Araki, Hideo, Katsuda, Yuko, Konishi, Masahiro, Matsunaga, Takahiro, Oe, Masashi, Ogane, Kunihiro, Sakai, Masato, Takahashi, Tomoko, Yamano, Takahiro, Yokoyama, Takuya, Ito, Hitomi, Katayama, Masayo, Kuroda, Emi, Ikeda, Toru, Kojo, Takuma, Yoshidome, Etsuo, Mizumachi, Rieko, Yamamoto, Akane, Yamasaki, Narihisa, Yamasaki, Yoshihiko, Wada, Jun, Eguchi, Jun, Higuchi, Chigusa, Katayama, Akihiro, Kinomura, Masaru, Kitagawa, Masashi, Kitamura, Shinji, Miyamoto, Satoshi, Morinaga, Hiroshi, Nakatsuka, Atsuko, Nojima, Ichiro, Shikata, Kenichi, Sugiyama, Hitoshi, Tanabe, Katsuyuki, Tsuji, Kenji, Uchida, Haruhito, Watanabe, Mayu, Hashimoto, Chie, Kato, Takahiro, Yamamoto, Sayaka, Wada, Takehiko, Fukagawa, Masafumi, Hamano, Naoto, Koizumi, Masahiro, Komaba, Hirotaka, Nakagawa, Yosuke, Iwamoto, Michiyo, Masutani, Kosuke, Katanosaka, Akane, Kiyota, Mayu, Uchi, Hikari, Ueda, Yuka, Yamamoto, Sonoka, Nagasu, Hajime, Itano, Seiji, Iwakura, Tsukasa, Kadoya, Hiroyuki, Kanda, Eiichiro, Kashihara, Naoki, Kidokoro, Kengo, Kondo, Megumi, Sasaki, Tamaki, Satoh, Minoru, Tokuyama, Atsuyuki, Umeno, Reina, Wada, Yoshihisa, Yamamoto, Toshiya, Yamanouchi, Yu, Abe, Masumi, Inukai, Yoko, Ogawa, Wataru, Asahara, Shunichiro, Fujii, Hideki, Goto, Shunsuke, Hirota, Yushi, Hosooka, Tetsuya, Kono, Keiji, Nishi, Shinichi, Okada, Yuko, Sakaguchi, Kazuhiko, Sugawara, Kenji, Takahashi, Michiko, Takai, Tomoko, Tamori, Yoshikazu, Watanabe, Kentaro, Kitajima, Miyu, Nishi, Misaki, Wada, Junko, Ito, Yasuhiko, Kamiya, Hideki, Asai, Akimasa, Asai, Nao, Asano, Saeko, Banno, Shogo, Ejima, Yohei, Hase, Hanako, Hayami, Tomohide, Himeno, Tatsuhito, Ishikawa, Takahiro, Ito, Mayumi, Iwagaitsu, Shiho, Kasagi, Rina, Kato, Yoshiro, Kato, Makoto, Kato, Koichi, Katsuno, Takayuki, Kawai, Miyuka, Kinashi, Hiroshi, Kondo, Masaki, Koshino, Masako, Matsuoka, Naoya, Morishita, Yoshiaki, Motegi, Mikio, Nakamura, Jiro, Shimoda, Hiromi, Sugiyama, Hirokazu, Tsunekawa, Shin, Yamaguchi, Makoto, Takahashi, Kazuyo, Watada, Hirotaka, Funayama, Takashi, Furukawa, Yasuhiko, Gohda, Tomohito, Goto, Hiromasa, Kaga, Hideyoshi, Kanaguchi, Yasuhiko, Kanazawa, Akio, Kaneko, Kayo, Kano, Toshiki, Kihara, Masao, Kimura, Shogo, Kobayashi, Takashi, Maiguma, Masayuki, Makita, Yuko, Mano, Satoshi, Mita, Tomoya, Miyatsuka, Takeshi, Murakoshi, Maki, Muto, Masahiro, Nakata, Masami, Nakata, Junichiro, Nishida, Yuya, Nohara, Nao, Ogihara, Takeshi, Sato, Daisuke, Sato, Junko, Sato, Hiroaki, Suzuki, Yusuke, Suzuki, Ruka, Suzuki, Hitoshi, Takagi, Miyuki, Tamura, Yoshifumi, Uchida, Toyoyoshi, Ueda, Seiji, Asawa, Miki, Miyaji, Minako, Nagashima, Eri, Shibata, Yoshie, Yanagisawa, Eri, Yamauchi, Toshimasa, Hirakawa, Yosuke, Nishi, Hiroshi, Shojima, Nobuhiro, Horikawa, Satoko, Nakayama, Yukiko, Yamada, Naoko, Omori, Yuki, Yano, Shintaro, Ioka, Miyabi, Kuwabara, Nahoko, Nagano, Remi, Nozawa, Megumi, Osawa, Yumi, Maegawa, Hiroshi, Kume, Shinji, Araki, Shinichi, Miyazawa, Itsuko, Morino, Katsutaro, Kawai, Ikuko, Sobata, Masumi, Takaoka, Motoko, Iwaita, Yasushi, Udagawa, Takashi, Inamori, Ami, Kawase, Aya, Yamanaka, Aya, Shimano, Hitoshi, Fujita, Akiko, Iwasaki, Hitoshi, Kai, Hirayasu, Osaki, Yoshinori, Saito, Chie, Sekiya, Motohiro, Tsunoda, Ryoya, Yamagata, Kunihiro, Nakamura, Rikako, Yamada, Aiko, Ohsugi, Mitsuru, Awazawa, Motoharu, Bouchi, Ryotaro, Hashimoto, Shota, Hashimoto, Makiko, Hisatake, Tomoko, Ihana, Noriko, Ishizuka, Koko, Izumi, Kazuo, Kajio, Hiroshi, Kobayashi, Michi, Kodani, Noriko, Maruyama, Koji, Matsumoto, Michihiro, Matsushita, Maya, Nakamura, Tomoka, Sugiyama, Takehiro, Tanabe, Akiyo, Terakawa, Aiko, Ueki, Kojiro, Orimo, Yuko, Ozawa, Takako, Takahira, Eriko, Yamasaki, Yoshimitsu, Haneda, Masakazu, Tomita, Tadahiro, Akimoto, Saori, Fujimoto, Akihiro, Ishihara, Kenji, Murakami, Chiho, Nishiyama, Akiyo, Toyonaga, Yukiko, Uozumi, Kana, Yamaji, Yukihiro, Shigehara, Tetsuya, Okajyo, Jun, Shimizu, Yukihiro, Iwasaki, Shingo, Fukao, Yuki, Furusho, Megumi, Nunokawa, Shintaro, Katagiri, Hideki, Izumi, Tomohito, Kaneko, Keizo, Kodama, Shinjiro, Miyazaki, Mariko, Munakata, Yuichiro, Nagasawa, Tasuku, Oe, Yuji, Sugawara, Hiroto, Takahashi, Kei, Hirata, Kazushige, Inomata, Keiko, Otomo, Shoko, Uchida, Taeko, Yamashita, Chigusa, Kiyosue, Arihiro, Tamura, Ryota, Dube, Francoi, Bolduc, Marilene, Talbot, Marie-Christine, Cham, Leslie, Lai, Vesta, Tse, Josephine, Jolly, Shivinder, Duck, Tabbatha, Lyle, Scott, Epp, Rachel, Galloway, Camille, Haskett, Susan, Matvienko, Elizabeta, Paulsen, Liam, Moist, Louise, Lozon, Zabrina, Ramsey, Tina, Whitmore, Brittany, Al-Zeer, Bader, Macleod, Paula, O'Sullivan, Aoife, Sheriff, Zainab, Tholl, Sam, Pandey, Amritanshu, Armstrong, Samantha, Gebeyehu, Bethelihem, Toth, Patrick, Goldenberg, Ronald, Jahangiriesmaili, Mahsa, Sanguila, Shariff, Suresh, Neethi, Talsania, Tanvi, Zalunardo, Nadia, Agharazii, Mohsen, Roussel, Marie-Pier, Saillant, Annie, Samson, France, Bajaj, Harpreet, Bhavsar, Miken, Dhall, Parul, Dhillon, Gagandeep, Grewal, Bhupinder, Nimbkar, Taniya, Madore, Francoi, Marcotte, Guylaine, Steen, Oren, Bullen, Mathura, Raguwaran, Shayani, Valleteau, Andre, Langlois, Marie-France, Brown, Christine, Steele, Andrew, Garrity, Melissa, Ghate, Taneera, Robinson, Holly, Tolibas, Michael, Tailor, Chetna, Elliott, Lauren, McClary-Wright, Christine, Boreky, Fadia, Fikry, Sameh, Ali, Ayesha, Barot, Chintankumar, Basily, Wagdy, Saram, Thisun, Varad, Vinay, Khandwala, Hasnain, Aguilera, Alex, Alvarez, Patricia, Gill, Balwinder, Huda, Nazihah, Navivala, Aamir, Pinto, Daniel, Bevilacqua, Micheli, Fung, Elaine, Hernandez, Geraldine, Mann, Puneet, Saini, Jaskiran, Rabasa-Lhoret, Remi, Bovan, Danijela, Devaux, Marie, Barnini, Cecilia, Leoncini, Giovanna, Manco, Luca, Nobili, Giulia, Piemontese, Matteo, Aucella, Filippo, Grifa, Rachele, Totaro, Francesco, La Manna, Gaetano, Capelli, Irene, Cianciolo, Giuseppe, Lerario, Sarah, Zappulo, Fulvia, Rosati, Alberto, Fani, Filippo, Spatoliatore, Giuseppe, Gesualdo, Loreto, Pesce, Francesco, Russo, Maria, Zippo, Maria, Cafiero, Cesira, Motta, Daria, Bianco, Simona, Bilucaglia, Donatella, Messa, Piergiorgio, Pavone, Laura, Tripodi, Federica, Vettoretti, Simone, Fioretto, Paola, Carraro, Gianni, Farnia, Filippo, Postal, Anna, D'Amelio, Alessandro, Cardone, Antonio, Piccinni, Giovanni, Aloisi, Annalisa, Scolari, Francesco, Alberici, Federico, Guerini, Alice, Saccà, Chiara, Salviani, Chiara, Zani, Roberta, DE NICOLA, Luca, Garofalo, Carlo, Elena Liberti, Maria, Minutolo, Roberto, Pennino, Luigi, Polese, Lucio, Mené, Paolo, Barberi, Simona, Falcone, Clorinda, Russo, Francesco, Caroppo, Maurizio, Santorelli, Gennaro, Rivera, Rodolfo, Santoro, Domenico, Giuffrida, Alfio, Zirino, Fortunata, Calvi, Cristina, Estienne, Luca, Gambaro, Giovanni, Gangemi, Concetta, Ortalda, Vittorio, Pessolano, Giuseppina, Grandaliano, Giuseppe, Baccaro, Rocco, Ferraro, Pietro, Mangiacapra, Roberto, Melandri, Marco, Foligno, Nadia, Quartagno, Rita, Vezzoli, Giuseppe, Brioni, Elena, and Group, EMPA-KIDNEY Collaborative more...

Subjects
chronic renal disease, empagliflozin, empa-kidney, General Medicine
Abstract

Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m2 of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m2 with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; PConclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo. (Funded by Boehringer Ingelheim and others; EMPA-KIDNEY ClinicalTrials.gov number, NCT03594110. opens in new tab; EudraCT number, 2017-002971-24. opens in new tab.) more...

Published
2023

7. An all-wales virtual reality project-innovation, design and collaboration to enhance healthcare education

Author

Marc Holmes, Craig Dyer, Sara Cook, Paul Twose, and Joanne Davies

Abstract

The potential for immersive technologies to augment healthcare training is gaining significant interest. However, its applicability and effectiveness are yet to be fully understood. This project was a response from a bid released by the Cardiff Capital Region to undertake a rapid innovation project, consisting of 3 main phases: 1) feasibility; 2) development; and 3) testing, across Welsh Health Boards. Project governance was provided via the Small Business Research Initiative (SBRI) in Clinical Excellence, a project board, and a project team with clinical and educational expertise, alongside Virtual Reality (VR) industry and academic partners. We aim to explore the formation of a virtual reality training package with a multi-centred collaborative project to overcome the current challenges of respiratory education, with a particular focus on tracheostomy care, to meet the challenges of the COVID-19 pandemic and beyond [1]. Phase 1 focused on the development of minimally viable solutions with a key focus on clinical content accuracy and education standards for single user learners. Phase 2 progressed to further develop the VR-based solutions including a multi-player system and virtual debriefing room, allowing the team to focus on key simulation-based learning best practice standards within the design and build [2]. Phase 3 is when system testing occurred over an 8-week period, across 6 Health Boards in NHS Wales involving over 100 multi-professional clinicians commencing in February 2022. On site hospital clinical education session feedback regarding use of the system and perceived opportunities were highly favourable in terms of ease of use, potential for VR in practice, and providing flexibility for mass training needs. Multi-user training was particularly well received. The limitations were lack of resource and time to combine a formal research project regarding the educational impact within busy health boards. This is planned for the next phase. Empirical evidence from other industries demonstrates VR technology is an effective and efficient way of improving training [3]. Developing VR solutions to support healthcare training needs involves a collaborative approach with Health Boards, industry, and academic partners. The design, build, and implementation approach can embed simulation best practice standards to form innovative educational solutions to the challenges seen in the delivery of mass healthcare education. Formal research is required to begin to measure such factors as education transference, patient care impact, and return on investment questions. 1. Chiang DH, Huang CC, Cheng SC, Cheng JC, Wu CH, Huang SS, Yang YY, Yang LY, Kao SY, Chen CH, Shulruf B. Immersive virtual reality (VR) training increases the self-efficacy of in-hospital healthcare providers and patient families regarding tracheostomy-related knowledge and care skills: A prospective pre–post study. Medicine. 2022;101(2):e28570–e28570. 2. Rossler K, Molloy MA, Pastva AM, Brown M, Xavier N. Healthcare Simulation Standards of Best Practice 3. Manolakis K, Papagiannakis G. Virtual Reality simulation streamlines medical training for healthcare professionals. Journal of dentistry. 2022;121:103987. more...

Published
2022
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9. Implementing the STEADY Wellness Program to Support Healthcare Workers throughout the COVID-19 Pandemic

Author

Melissa B. Korman, Rosalie Steinberg, Lina Gagliardi, Brenda Stewart, Carmen Llanos Acero, Joanne Davies, Robert Maunder, Thomas Walker, Tracey DasGupta, Lisa DiProspero, Mark Sinyor, and Janet Ellis

Subjects
Health Information Management, Leadership and Management, Health Policy, Health Informatics
Abstract

The COVID-19 pandemic has posed an ongoing threat to the mental wellbeing of countless individuals worldwide, with healthcare workers at particularly high risk. We developed the STEADY staff wellness program prior to the pandemic based on the available literature and input from stakeholders, guided by the Knowledge-to-Action (KTA) Implementation Science Framework. We quickly adapted the STEADY program for implementation in selected high-need units within Canada’s largest trauma hospital during the pandemic’s first wave. This brief report describes implementation of the STEADY program, retroactively applying the structure of the Knowledge-to-Action Implementation Science Framework to the practical steps taken. We identified the importance of more frequent, shorter contact with HCWs that occurred in-person, with an emphasis on peer support. A flexible approach with strong support from hospital leadership were key facilitators. Our findings suggest that a flexible approach to practical program implementation, theoretically underpinned in best-practices, can result in an acceptable program that promotes increased HCW wellbeing during a pandemic. more...

Published
2022

10. Natural Protection From Type 1 Diabetes in NOD Mice Is Characterized by a Unique Pancreatic Islet Phenotype

Author

Joanne Boldison, Joanne Davies, F. Susan Wong, and Terri C. Thayer

Subjects
CD4-Positive T-Lymphocytes, 0301 basic medicine, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Nod, Biology, Islets of Langerhans, Mice, 03 medical and health sciences, 0302 clinical medicine, Antigens, CD, Internal Medicine, medicine, Animals, CTLA-4 Antigen, NOD mice, Type 1 diabetes, geography, geography.geographical_feature_category, Cluster of differentiation, Pancreatic islets, FOXP3, Forkhead Transcription Factors, Flow Cytometry, medicine.disease, Islet, Diabetes Mellitus, Type 1, 030104 developmental biology, medicine.anatomical_structure, Immunology, Female, Integrin alpha Chains, CD8
Abstract

The non-obese diabetic (NOD) mouse develops spontaneous type 1 diabetes, with some features of disease that are very similar to the human disease. However, a proportion of NOD mice are naturally-protected from developing diabetes, and currently studies characterising this cohort are very limited. Here, using both immunofluorescence and multi-parameter flow cytometry we focus on the pancreatic islet morphology and immune infiltrate observed in naturally-protected NOD mice. We show that naturally-protected NOD mice are characterised by an increased frequency of insulin-containing, smaller sized, pancreatic islets. Although mice remain diabetes free, florid immune infiltrate remains. However, this immune infiltrate is skewed towards a regulatory phenotype in both T and B-cell compartments. Pancreatic islets have an increased frequency of IL-10 producing B cells and associated cell surface markers. Resident memory CD69+CD8+ T cells show a significant shift towards reduced CD103 expression, while CD4+ T cells have increased FoxP3+CTLA4+ expression. These data indicate that naturally-protected NOD mice have a unique islet signature and provide new insight into regulatory mechanisms within pancreatic islets. more...

Published
2021
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11. Differentiating MHC-Dependent and -Independent Mechanisms of Lymph Node Stromal Cell Regulation of Proinsulin-Specific CD8+ T Cells in Type 1 Diabetes

Author

James A. Pearson, F. Susan Wong, Joanne Davies, Stephanie J. Hanna, Li Wen, and Terri C. Thayer

Subjects
0301 basic medicine, Stromal cell, biology, Chemistry, Endocrinology, Diabetes and Metabolism, Peripheral tolerance, CD28, 030209 endocrinology & metabolism, Major histocompatibility complex, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Internal Medicine, biology.protein, Lymph node stromal cell, Cancer research, Cytotoxic T cell, CD8, Proinsulin
Abstract

Lymph node stromal cells (LNSC) are essential for providing and maintaining peripheral self-tolerance of potentially autoreactive cells. In type 1 diabetes, proinsulin-specific CD8+T-cells, escaping central and peripheral tolerance, contribute to beta-cell destruction. Using G9Cα-/-CD8+T-cells specific for proinsulin, we studied the mechanisms by which LNSC regulate low-avidity autoreactive cells in the nonobese diabetic (NOD) mouse model of type 1 diabetes. Whereas MHC-matched NOD-LNSC significantly reduced G9Cα-/-CD8+T-cell cytotoxicity and DC-induced proliferation, they failed to sufficiently regulate T-cells stimulated by anti-CD3/CD28. In contrast, non-MHC matched, control C57BL/6 mouse LNSC suppressed T-cell receptor engagement by anti-CD3/CD28 via MHC-independent mechanisms. This C57BL/6-LNSC suppression was maintained even after removal of the LNSC, demonstrating a direct effect of LNSC on T-cells, modifying antigen sensitivity and effector function. Thus, our results suggest that a loss of NOD-LNSC MHC-independent suppressive mechanisms may contribute to diabetes development. more...

Published
2020
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12. Gene expression profiling reveals B cells are highly educated by the pancreatic environment during autoimmune diabetes

Author

Joanne Boldison, Jessica Hopkinson, Joanne Davies, James A Pearson, Pia Leete, Sarah Richardson, Noel G Morgan, and F. Susan Wong

Abstract

B cells play an important role in driving the development of type 1 diabetes, however, it remains unclear how they contribute to local beta-cell destruction during disease progression. Using gene expression profiling of B cell subsets in the pancreas and pancreatic lymph nodes, we reveal that B cells are highly modified by the inflamed pancreatic tissue and can be distinguished by their transcriptional profile from those in the lymph node. We identified both a discrete and a core shared gene expression profile in islet CD19+CD138- and CD19+CD138+ B cell subsets, the latter known to have enriched autoreactivity during diabetes development. Upon localisation to pancreatic islets, CD138+ B cells overexpressed genes associated with adhesion molecules and growth factors compared to CD138- B cells. Their shared signature displayed gene expression changes related to the differentiation of antibody-secreting cells and gene regulatory networks associated with interferon signalling pathways, pro-inflammatory cytokines and toll-like receptor activation. Finally, abundant TLR7 expression was detected in islet B cells, and was enhanced specifically in CD138+ B cells. Our study, therefore, provides a detailed transcriptional analysis of islet B cells identifying specific gene signatures and interaction networks that point towards a functional role for B cells in driving autoimmune diabetes. more...

Published
2022
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15. Trends in physical activity participation and the impact of integrated campaigns among Australian adults, 1997–99

Author

Adrian Bauman, Tim Armstrong, Joanne Davies, Neville Owen, Wendy Brown, Bill Bellew, and Philip Vita

Subjects
Public aspects of medicine, RA1-1270
Abstract

Abstract Objectives: To determine whether awareness of the moderate physical activity message and prevalence of participation changed among Australian adults between 1997 and 1999, and if changes differed across Australia. Methods: Data were compared on awareness of the moderate physical activity message and on physical activity participation from identical national physical activity surveys in 1997 and 1999. Results: In 1999, following integrated public health efforts, recognition of the Active Australia campaign was substantially higher in NSW/ACT (61.7%) than elsewhere (29.3%). Knowledge about benefits of moderate activity increased between 1997 and 1999, more so in States with public health campaigns. National participation in ‘sufficient physical activity’ declined between 1997 and 1999, from 63% to 57%, but the decline was smaller in NSW/ACT (4.4%) than in the other States (6.0%). Conclusions and implications: Declining trends in physical activity in Australia require increased public health investments, including strategic planning and public education, such as occurred in NSW (1997/98). more...

Published
2003
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16. Dendritic cells license regulatory B cells to produce IL-10 and mediate suppression of antigen-specific CD8 T cells

Author

Joanne Davies, Larissa Camargo da Rosa, F. Susan Wong, Li Wen, and Joanne Boldison

Subjects
Lipopolysaccharides, 0301 basic medicine, Regulatory B cells, Immunology, Nod, CD8-Positive T-Lymphocytes, Biology, Article, Epitopes, 03 medical and health sciences, 0302 clinical medicine, Antigens, CD, Mice, Inbred NOD, Immune Tolerance, Animals, Insulin, Immunology and Allergy, Cytotoxic T cell, NOD mice, Immunosuppression Therapy, B-Lymphocytes, Regulatory, Innate immune system, Models, Immunological, Cell Differentiation, Dendritic Cells, Dendritic cell, Interleukin-10, Cell biology, Interleukin 10, Diabetes Mellitus, Type 1, Phenotype, 030104 developmental biology, Infectious Diseases, TLR4, Cytokines, 030215 immunology
Abstract

Regulatory B cells (Bregs) suppress and reduce autoimmune pathology. However, given the variety of Breg subsets, the role of Bregs in the pathogenesis of type 1 diabetes is still unclear. Here, we dissect this fundamental mechanism. We show that natural protection from type 1 diabetes in nonobese diabetic (NOD) mice is associated with increased numbers of IL-10-producing B cells, while development of type 1 diabetes in NOD mice occurs in animals with compromised IL-10 production by B cells. However, B cells from diabetic mice regain IL-10 function if activated by the innate immune receptor TLR4 and can suppress insulin-specific CD8 T cells in a dendritic cell (DC)-dependent, IL-10-mediated fashion. Suppression of CD8 T cells is reliant on B-cell contact with DCs. This cell contact results in deactivation of DCs, inducing a tolerogenic state, which in turn can regulate pathogenic CD8 T cells. Our findings emphasize the importance of DC–Breg interactions during the development of type 1 diabetes. more...

Published
2019
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17. Phenotypically distinct anti-insulin B cells repopulate pancreatic islets after anti-CD20 treatment in NOD mice

Author

Lucy Buckingham, Joanne Davies, Joanne Boldison, Larissa Camargo da Rosa, Li Wen, and F. Susan Wong

Subjects
0301 basic medicine, Genetically modified mouse, Endocrinology, Diabetes and Metabolism, Population, Autoimmunity, Mice, Transgenic, 030209 endocrinology & metabolism, Biology, Article, CD19, Immune tolerance, Islets of Langerhans, Mice, 03 medical and health sciences, 0302 clinical medicine, Mice, Inbred NOD, Anti-insulin B cells, Immune Tolerance, Internal Medicine, medicine, Animals, Humans, Insulin, education, Pancreas, NOD mice, CD20, B-Lymphocytes, education.field_of_study, Pancreatic islets, Antibodies, Monoclonal, Antigens, CD20, Flow Cytometry, 3. Good health, Type 1 diabetes, Diabetes Mellitus, Type 1, 030104 developmental biology, medicine.anatomical_structure, biology.protein, Cancer research, Female, Immunotherapy, Anti-CD20 treatment
Abstract

Aims/hypothesis Autoreactive B cells escape immune tolerance and contribute to the pathogenesis of type 1 diabetes. While global B cell depletion is a successful therapy for autoimmune disease, the fate of autoreactive cells during this treatment in autoimmune diabetes is unknown. We aimed to identify and track anti-insulin B cells in pancreatic islets and understand their repopulation after anti-CD20 treatment. Methods We generated a double transgenic system, the VH125.hCD20/NOD mouse. The VH125 transgenic mouse, expressing an increased frequency of anti-insulin B cells, was crossed with a human CD20 (hCD20) transgenic mouse, to facilitate B cell depletion using anti-CD20. B cells were analysed using multiparameter and ImageStream flow cytometry. Results We demonstrated that anti-insulin B cells were recruited to the pancreas during disease progression in VH125.hCD20/NOD mice. We identified two distinct populations of anti-insulin B cells in pancreatic islets, based on CD19 expression, with both populations enriched in the CD138int fraction. Anti-insulin B cells were not identified in the plasma-cell CD138hi fraction, which also expressed the transcription factor Blimp-1. After anti-CD20 treatment, anti-insulin B cells repopulated the pancreatic islets earlier than non-specific B cells. Importantly, we observed that a CD138intinsulin+CD19− population was particularly enriched after B cell depletion, possibly contributing to the persistence of disease still observed in some mice after anti-CD20 treatment. Conclusions/interpretation Our observations may indicate why the loss of C-peptide is only temporarily delayed following anti-CD20 treatment in human type 1 diabetes. Electronic supplementary material The online version of this article (10.1007/s00125-019-04974-y) contains peer-reviewed but unedited supplementary material, which is available to authorised users. more...

Published
2019
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18. Diabetic foot ulcer incidence and survival with improved diabetic foot services: an 18‐year study

Author

R. B. Paisey, A. Abbott, C. F. Paisey, D. Walker, Rebecca Birch, Belinda Bowen, Roger Brown, Cheryl Clark, Richard Collings, Steve Cutts, Joanne Davies, Sean Ellin, Kerry‐Ann Evans, Rob Fisher, Sam Glasser, Martyn Hillstead, Gemma Hine, Sarah Levi, Amanda Martin, Lauren Mackintosh, Sadie Phillips, Ella Rawlinson, Anne‐Marie Shepperd, Kerrie Spicer, Su Stewart, Sam Stocker, Harriet Tailford, Justine Tansley, Hannah Uglow, Adam Widgery, Jen Williams, and Samuel Darke more...

Subjects
Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, 03 medical and health sciences, Research: Care Delivery, 0302 clinical medicine, Endocrinology, Diabetic Neuropathies, Internal medicine, Internal Medicine, medicine, Humans, Community Health Services, 030212 general & internal medicine, Podiatry, Care Delivery, Research Articles, Aged, Proportional Hazards Models, Wound Healing, Vascular disease, business.industry, Proportional hazards model, Incidence, Incidence (epidemiology), Diabetic foot care, Middle Aged, medicine.disease, Diabetic foot, Diabetic Foot, Diabetic foot ulcer, Health Care Surveys, Female, business, Diabetic Angiopathies, Foot (unit), Follow-Up Studies
Abstract

Aims To ascertain the effects of improvements in diabetic foot services over 18 years on incidence of diabetic foot ulceration. We also compared survival time from first ulcer development with presence of neuropathy, peripheral vascular disease, age and healing. Methods Persons with new ulceration and those at high risk of ulcer development were referred to community podiatry from 1998. Their details were recorded, with verbal consent, on a central database. The effects of neuropathy, peripheral vascular disease, healing and age on survival were analysed by Cox proportional hazards ratios. Results The incidence of first ulcer presentation decreased from 11.1 to 6.1 per 1000 persons between 2003 to 2017 (P, What's new? Prevention of diabetic foot ulceration has been difficult to acheiveSurvival after diabetic foot ulceration has historically been poorThis study has shown reduction in first diabetes related foot ulceration with improved foot care services Participant survival after development of first diabetic foot ulceation was longer than in recent reports especially for those under 65 years of age, where ulcers healed, and in those without peripheral vascular diseaseAdequate commissioning of diabetic foot care services is necessary to prevent first foot ulcerationCounselling for younger patients with diabetic foot ulceration can be more posisitve more...

Published
2019
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19. Using gold nanoparticles for enhanced intradermal delivery of poorly soluble auto-antigenic peptides

Author

Bernard Malissen, Martina A. McAteer, James Caradoc Birchall, Colin M. Dayan, Yotam Levin, F. Susan Wong, Sandrine Henri, Joanne Davies, Efrat Kochba, Ravinder K. Singh, Jan Mous, Camille Malosse, Sion Coulman, Laboratoire des mécanismes réactionnels (DCMR), École polytechnique (X)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Cardiff University, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Weizmann Institute of Science [Rehovot, Israël], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU) more...

Subjects
Injections, Intradermal, T-Lymphocytes, Biomedical Engineering, Metal Nanoparticles, Pharmaceutical Science, Medicine (miscellaneous), Mice, Transgenic, Bioengineering, C-C chemokine receptor type 7, Peptide, Spleen, 02 engineering and technology, 03 medical and health sciences, Autoantigen, In vivo, Intradermal, medicine, Animals, General Materials Science, Amino Acid Sequence, Intradermal injection, Antigens, Receptor, Cell Proliferation, Skin, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Microneedle, Dendritic Cells, Hydrophobic, 021001 nanoscience & nanotechnology, Mice, Inbred C57BL, Phenotype, Lymphatic system, medicine.anatomical_structure, Solubility, chemistry, Needles, Colloidal gold, Biophysics, [SDV.IMM]Life Sciences [q-bio]/Immunology, Molecular Medicine, Gold, Peptides, 0210 nano-technology
Abstract

International audience; Ultra-small 1-2 nm gold nanoparticles (NP) were conjugated with a poorly-soluble peptide auto-antigen, associated with type 1 diabetes, to modify the peptide pharmacokinetics, following its intradermal delivery. Peptide distribution was characterized, in vivo, after delivery using either conventional intradermal injection or a hollow microneedle device. The poorly-soluble peptide was effectively presented in distant lymph nodes (LN), spleen and draining LN when conjugated to the nanoparticles, whereas peptide alone was only presented in the draining LN. By contrast, nanoparticle conjugation to a highly-soluble peptide did not enhance in vivo distribution. Transfer of both free peptide and peptide-NPs from the skin to LN was reduced in mice lacking lymphoid homing receptor CCR7, suggesting that both are actively transported by migrating dendritic cells to LN. Collectively, these data demonstrate that intradermally administered ultra-small gold nanoparticles can widen the distribution of poorly-soluble auto-antigenic peptides to multiple lymphoid organs, thus enhancing their use as potential therapeutics. more...

Published
2021
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20. Natural Protection From Type 1 Diabetes in Non Obese Diabetic (Nod) Mice is Characterized by a Unique Pancreatic Islet Phenotype

Author

F. Susan Wong, Terri C. Thayer, Joanne Davies, and Joanne Boldison

Subjects
geography, Type 1 diabetes, geography.geographical_feature_category, Cluster of differentiation, Pancreatic islets, FOXP3, Nod, Biology, Islet, medicine.disease, medicine.anatomical_structure, Immunology, medicine, CD8, NOD mice
Abstract

The non-obese diabetic (NOD) mouse develops spontaneous type 1 diabetes, with some features of disease that are very similar to the human disease. However, a proportion of NOD mice are naturally-protected from developing diabetes, and currently studies characterising this cohort are very limited. Here, using both immunofluorescence and multi-parameter flow cytometry we focus on the pancreatic islet morphology and immune infiltrate observed in naturally-protected NOD mice. We show that naturally-protected NOD mice are characterised by an increased frequency of insulin-containing, smaller sized, pancreatic islets. Although mice remain diabetes free, florid immune infiltrate remains. However, this immune infiltrate is skewed towards a regulatory phenotype in both T and B-cell compartments. Pancreatic islets have an increased frequency of IL-10 producing B cells and associated cell surface markers. Resident memory CD69+CD8+T cells show a significant shift towards reduced CD103 expression, while CD4+T cells have increased FoxP3+CTLA4+expression. These data indicate that naturally-protected NOD mice have a unique islet signature and provide new insight into regulatory mechanisms within pancreatic islets. more...

Published
2021
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21. Capturing the impact of Co-Creation: poetry and street art in Iztapalapa

Author

Joanne Davies, Osorio-Saez, E., Sandoval-Hernández, A., and Horvath, C.

Abstract

This chapter seeks to test through a case study how transformative change resulting from Co-Creation can be evidenced and measured using a quasi experimental mixed-method approach. The first section focuses on the design of the case study, a poetry workshop aimed at students aged 14–17, initiated at a secondary school in Iztapalapa, Mexico City, by a group of researchers in collaboration with four poets, a street artist, a governmental organization belonging to the Mexican Ministry of Culture, the teachers and non-academic staff from a lower secondary school. The second section explains the design of the research methods and analyses changes in how workshop participants perceive their neighbourhood and themselves as agents of change in their school and wider community. The final section assesses the effectiveness of the both the Co-Creation workshop and the methodology used to measure its impact. Our final comments suggest that to be more efficient, the evaluation of Co-Creation workshops need to focus on both the intangible (knowledge, understanding, emotions) and the creative (poetry, painting) outcomes in ways that combine research methods from the North with strategies inspired by the epistemologies of the South. more...

Published
2020
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22. Comparison of the peripheral blood eosinophil count using near-patient testing and standard automated laboratory measurement in healthy, asthmatic and COPD subjects

Author

Helen Jeffers, Clare Connolly, Joanne Davies, Catherine Borg, Richard Russell, Mona Bafadhel, and K Hambleton

Subjects
Adult, Male, medicine.medical_specialty, near-patient testing, Exacerbation, Point-of-care testing, Short Report, International Journal of Chronic Obstructive Pulmonary Disease, 030204 cardiovascular system & hematology, Workflow, chronic obstructive pulmonary disease, Leukocyte Count, Pulmonary Disease, Chronic Obstructive, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Internal medicine, Humans, Medicine, Aged, Asthma, Automation, Laboratory, COPD, Venipuncture, business.industry, Case-control study, Reproducibility of Results, General Medicine, Middle Aged, asthma, Eosinophil, medicine.disease, Eosinophils, medicine.anatomical_structure, 030228 respiratory system, Point-of-Care Testing, Case-Control Studies, Predictive value of tests, Immunology, Female, business
Abstract

Kirsty Hambleton, Clare M Connolly, Catherine Borg, Joanne H Davies, Helen P Jeffers, Richard EK Russell, Mona Bafadhel Respiratory Medicine Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK Abstract: Near-patient testing (NPT) allows clinical decisions to be made in a rapid and convenient manner and is often cost effective. In COPD the peripheral blood eosinophil count has been demonstrated to have utility in providing prognostic information and predicting response to treatment during an acute exacerbation. For this potential to be achieved having a reliable NPT of blood eosinophil count would be extremely useful. Therefore, we investigated the use of the HemoCue® WBC Diff System and evaluated its sensitivity and specificity in healthy, asthmatic and COPD subjects. This method requires a simple skin prick of blood and was compared to standard venepuncture laboratory analysis. The HemoCue® WBC Diff System measured the peripheral blood eosinophil count in healthy, asthma and COPD subjects with very close correlation to the eosinophil count as measured by standard venepuncture. The correlations were unaffected by disease status. This method for the measurement of the peripheral blood eosinophil count has the potential to provide rapid near-patient results and thus influence the speed of management decisions in the treatment of airway diseases. Keywords: asthma, chronic obstructive pulmonary disease, eosinophils, near-patient testing more...

Published
2017
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23. Differentiating MHC-Dependent and -Independent Mechanisms of Lymph Node Stromal Cell Regulation of Proinsulin-Specific CD8

Author

Terri C, Thayer, Joanne, Davies, James A, Pearson, Stephanie J, Hanna, Li, Wen, and F Susan, Wong

Subjects
Mice, Diabetes Mellitus, Type 1, Mice, Inbred NOD, Histocompatibility Antigens Class II, Animals, Dendritic Cells, Lymph Nodes, CD8-Positive T-Lymphocytes, Stromal Cells, Immunology and Transplantation, Proinsulin
Abstract

Lymph node stromal cells (LNSC) are essential for providing and maintaining peripheral self-tolerance of potentially autoreactive cells. In type 1 diabetes, proinsulin-specific CD8(+) T cells, escaping central and peripheral tolerance, contribute to β-cell destruction. Using G9Cα(−/−)CD8(+) T cells specific for proinsulin, we studied the mechanisms by which LNSC regulate low-avidity autoreactive cells in the NOD mouse model of type 1 diabetes. Whereas MHC-matched NOD-LNSC significantly reduced G9Cα(−/−)CD8(+) T-cell cytotoxicity and dendritic cell–induced proliferation, they failed to sufficiently regulate T cells stimulated by anti-CD3/CD28. In contrast, non-MHC–matched, control C57BL/6 mouse LNSC suppressed T-cell receptor engagement by anti-CD3/CD28 via MHC-independent mechanisms. This C57BL/6-LNSC suppression was maintained even after removal of the LNSC, demonstrating a direct effect of LNSC on T cells, modifying antigen sensitivity and effector function. Thus, our results suggest that a loss of NOD-LNSC MHC-independent suppressive mechanisms may contribute to diabetes development. more...

Published
2019

24. Improving the provision of clinical skills teaching for undergraduate medical students during their psychiatry placement: a trainee-led quality improvement project

Author

Melissa Buckley, Joanne Davies, and Gabrielle Churchhouse

Subjects
Adult, Male, Psychiatry, medicine.medical_specialty, Quality management, Students, Medical, Quality Improvement, 030227 psychiatry, Clinical knowledge, 03 medical and health sciences, Psychiatry and Mental health, Young Adult, 0302 clinical medicine, medicine, Humans, Female, 030212 general & internal medicine, Clinical Competence, Curriculum, Communication skills, Psychology, Clinical skills, Education, Medical, Undergraduate
Abstract

Objective: To increase the provision of clinical skills training during their psychiatry placement by providing a new teaching course to enhance both their clinical knowledge and communication skills. Method: We delivered a pilot teaching course consisting of five workshops (incorporating facilitated, ‘near peer’ role-play) during the students’ psychiatry placement. Qualitative and quantitative feedback was collected pre- and post-course to allow for development of the course. Results: Data collected indicated that all students found the course a valuable addition to their usual teaching. They indicated that their confidence in their ability to assess patients with common clinical problems improved. Conclusions: This trainee-led course was easily integrated into the curriculum and received positive feedback from students. It may have enhanced students’ confidence and readiness for exams but this will require further examination of objective assessments and ongoing research to establish this. more...

Published
2019

25. Altered gut microbiota activate and expand insulin B15-23-Reactive CD8+ T-Cells

Author

Simone Cuff, Li Wen, Jeremy Warden-Smith, Joanne Davies, F. Susan Wong, M. D. Lewis, James A. Pearson, Larissa Camargo da Rosa, Dimitri Kakabadse, and Jian Peng

Subjects
Male, 0301 basic medicine, Receptors, Antigen, T-Cell, alpha-beta, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, T cell, 030209 endocrinology & metabolism, Nod, CD8-Positive T-Lymphocytes, Biology, Gut flora, Diabetes Mellitus, Experimental, Mice, 03 medical and health sciences, 0302 clinical medicine, Mice, Inbred NOD, Diabetes mellitus, Internal Medicine, medicine, Animals, Cytotoxic T cell, Enrofloxacin, Type 1 diabetes, Insulin, medicine.disease, biology.organism_classification, Gastrointestinal Microbiome, 030104 developmental biology, medicine.anatomical_structure, Immunology, Immunology and Transplantation, CD8, Proinsulin
Abstract

Insulin is a major autoantigen in type 1 diabetes, targeted by both CD8 and CD4 T-cells. We studied an insulin-reactive T-cell receptor (TCR) alpha-chain transgenic non-obese diabetic (NOD) mouse on a TCRCα and proinsulin2 (PI2)-deficient background, designated as A22Cα-/-PI2-/-NOD mice. These mice develop a low incidence of autoimmune diabetes. To test the role of gut microbiota on diabetes development in this model system, we treated the A22Cα-/-PI2-/-NOD mice with enrofloxacin, a broad-spectrum antibiotic. The treatment led to male mice developing accelerated diabetes. We found that enrofloxacin increased the frequency of the insulin-reactive CD8+ T-cells and activated the cells in the Peyer’s patches (PP) and pancreatic lymph nodes (PLNs), together with induction of immunological effects on the antigen-presenting cell populations. The composition of gut microbiota differed between the enrofloxacin-treated and untreated mice and also between the enrofloxacin-treated mice that developed diabetes, compared with those that remained normoglycemic. Our results provide evidence that the composition of the gut microbiota is important for determining the expansion and activation of insulin-reactive CD8+ T-cells. more...

Published
2019

26. Designing interprofessional simulation based faculty development in a new women and children's hospital in the Middle East: A pilot study

Author

Joanne Davies, Guy Brisseau, Barbara J. Blackie, Ella A. Scott, Joseph B. Shumway, and Elaine L. Sigalet

Subjects
Research design, 020205 medical informatics, التغذية الراجعة, Convenience sample, تطوير عضو هيئة التدريس المبني على المحاكاة, 02 engineering and technology, Simulation based learning, Feedback, Simulation based faculty development, 03 medical and health sciences, 0302 clinical medicine, معلمي الطب, 0202 electrical engineering, electronic engineering, information engineering, Medicine, 030212 general & internal medicine, Simulation based, Competence (human resources), Interprofessional education, lcsh:R5-920, Medical education, business.industry, Medical educators, Cognition, General Medicine, التعلم المبني على المحاكاة, التعليم المتداخل بين التخصصات, Faculty development, lcsh:Medicine (General), business
Abstract

ObjectivesThis study sheds light on information for clinical educators interested in designing interprofessional simulation based faculty development initiatives.MethodsA one group pre- and post-test design with a convenience sample was used to examine the relationship between participant knowledge of simulation based learning and effective feedback and the impact of pre-course eLearning on participant cognitive entry behaviours and achievement.ResultsThere were significant improvements in aggregate MCQ scores, [(t (39) = 4.08, p more...

Published
2016
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28. Loss of CXCR3 expression on memory B cells in individuals with long-standing type 1 diabetes

Author

David Price, Daniel Farewell, Li Wen, Gareth Dunseath, Joanne Davies, Stephanie J. Hanna, F. Susan Wong, Claire N. Hocter, Wendy Powell, Colin M. Dayan, Stephen D. Luzio, Emma J. S. Robinson, and Kristin Ladell more...

Subjects
0301 basic medicine, Adult, Male, Receptors, CXCR3, Endocrinology, Diabetes and Metabolism, T-Lymphocytes, B220, Autoimmunity, CXCR3, medicine.disease_cause, Article, 03 medical and health sciences, Chemokine receptor, Young Adult, 0302 clinical medicine, Internal Medicine, medicine, CXCL10, Humans, CXCL11, fas Receptor, Memory B cell, CD24, B cell, Type 1 diabetes, B-Lymphocytes, B cells, business.industry, medicine.disease, 3. Good health, Chemokine CXCL11, Tumor Necrosis Factor Receptor Superfamily, Member 7, 030104 developmental biology, medicine.anatomical_structure, Diabetes Mellitus, Type 1, Immunology, CD95, Leukocyte Common Antigens, BAFF, Female, Chemokines, business, 030215 immunology
Abstract

Aims/hypothesis Islet-specific autoantibodies can predict the development of type 1 diabetes. However, it remains unclear if B cells, per se, contribute to the causal pancreatic immunopathology. We aimed to identify phenotypic signatures of disease progression among naive and memory B cell subsets in the peripheral blood of individuals with type 1 diabetes. Methods A total of 69 participants were recruited across two separate cohorts, one for discovery purposes and the other for validation purposes. Each cohort comprised two groups of individuals with type 1 diabetes (one with newly diagnosed type 1 diabetes and the other with long-standing type 1 diabetes) and one group of age- and sex-matched healthy donors. The phenotypic characteristics of circulating naive and memory B cells were investigated using polychromatic flow cytometry, and serum concentrations of various chemokines and cytokines were measured using immunoassays. Results A disease-linked phenotype was detected in individuals with long-standing type 1 diabetes, characterised by reduced C-X-C motif chemokine receptor 3 (CXCR3) expression on switched (CD27+IgD−) and unswitched (CD27intermediateIgD+) memory B cells. These changes were associated with raised serum concentrations of B cell activating factor and of the CXCR3 ligands, chemokine (C-X-C motif) ligand (CXCL)10 and CXCL11. A concomitant reduction in CXCR3 expression was also identified on T cells. Conclusions/interpretation Our data reveal a statistically robust set of abnormalities that indicate an association between type 1 diabetes and long-term dysregulation of a chemokine ligand/receptor system that controls B cell migration. Electronic supplementary material The online version of this article (10.1007/s00125-018-4651-x) contains peer-reviewed but unedited supplementary material, which is available to authorised users. more...

Published
2018

29. B cell depletion reduces T cell activation in pancreatic islets in a murine autoimmune diabetes model

Author

Joanne Davies, Evy De Leenheer, Larissa Camargo da Rosa, F. Susan Wong, Li Wen, and Joanne Boldison

Subjects
0301 basic medicine, Endocrinology, Diabetes and Metabolism, T cell, Regulatory B cells, T-Lymphocytes, B cell depletion, Mice, Transgenic, Lymphocyte Activation, T-Lymphocytes, Regulatory, Article, 03 medical and health sciences, Islets of Langerhans, Mice, 0302 clinical medicine, Mice, Inbred NOD, Insulin-Secreting Cells, Internal Medicine, medicine, Animals, Humans, Transgenes, B cell, NOD mice, CD86, Inflammation, B cells, B-Lymphocytes, Mice, Inbred BALB C, Chemistry, Pancreatic islets, Antibodies, Monoclonal, medicine.disease, Antigens, CD20, 3. Good health, Interleukin-10, 030104 developmental biology, medicine.anatomical_structure, Type 1 diabetes, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Cancer research, Female, Insulitis, CD80, 030215 immunology
Abstract

Aims/hypothesis Type 1 diabetes is a T cell-mediated autoimmune disease characterised by the destruction of beta cells in the islets of Langerhans, resulting in deficient insulin production. B cell depletion therapy has proved successful in preventing diabetes and restoring euglycaemia in animal models of diabetes, as well as in preserving beta cell function in clinical trials in the short term. We aimed to report a full characterisation of B cell kinetics post B cell depletion, with a focus on pancreatic islets. Methods Transgenic NOD mice with a human CD20 transgene expressed on B cells were injected with an anti-CD20 depleting antibody. B cells were analysed using multivariable flow cytometry. Results There was a 10 week delay in the onset of diabetes when comparing control and experimental groups, although the final difference in the diabetes incidence, following prolonged observation, was not statistically significant (p = 0.07). The co-stimulatory molecules CD80 and CD86 were reduced on stimulation of B cells during B cell depletion and repopulation. IL-10-producing regulatory B cells were not induced in repopulated B cells in the periphery, post anti-CD20 depletion. However, the early depletion of B cells had a marked effect on T cells in the local islet infiltrate. We demonstrated a lack of T cell activation, specifically with reduced CD44 expression and effector function, including IFN-γ production from both CD4+ and CD8+ T cells. These CD8+ T cells remained altered in the pancreatic islets long after B cell depletion and repopulation. Conclusions/interpretation Our findings suggest that B cell depletion can have an impact on T cell regulation, inducing a durable effect that is present long after repopulation. We suggest that this local effect of reducing autoimmune T cell activity contributes to delay in the onset of autoimmune diabetes. Electronic supplementary material The online version of this article (10.1007/s00125-018-4597-z) contains peer-reviewed but unedited supplementary material, which is available to authorised users. more...

Published
2018

30. Proinsulin Expression Shapes the TCR Repertoire but Fails to Control the Development of Low-Avidity Insulin-Reactive CD8+ T Cells

Author

David Price, Terri C. Thayer, Dimitri Kakabadse, F. Susan Wong, Joanne Davies, James E. McLaren, Peter Huw Morgan, Kristin Ladell, James A. Pearson, Li Wen, Evy De Leenheer, Amy Phillips, and Kelly L. Miners more...

Subjects
CD4-Positive T-Lymphocytes, 0301 basic medicine, Receptors, Antigen, T-Cell, alpha-beta, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, T cell, Antibody Affinity, Mice, Transgenic, CD8-Positive T-Lymphocytes, Biology, Mice, 03 medical and health sciences, 0302 clinical medicine, Antigen, Mice, Inbred NOD, Internal Medicine, medicine, Animals, Insulin, Cytotoxic T cell, Proinsulin, NOD mice, T-cell receptor, R1, Cell biology, Diabetes Mellitus, Type 1, 030104 developmental biology, medicine.anatomical_structure, Immunology, Immunology and Transplantation, CD8, 030215 immunology
Abstract

NOD mice, a model strain for human type 1 diabetes, express proinsulin (PI) in the thymus. However, insulin-reactive T cells escape negative selection, and subsequent activation of the CD8(+) T-cell clonotype G9C8, which recognizes insulin B15-23 via an αβ T-cell receptor (TCR) incorporating TRAV8-1/TRAJ9 and TRBV19/TRBJ2-3 gene rearrangements, contributes to the development of diabetes. In this study, we used fixed TRAV8-1/TRAJ9 TCRα-chain transgenic mice to assess the impact of PI isoform expression on the insulin-reactive CD8(+) T-cell repertoire. The key findings were: 1) PI2 deficiency increases the frequency of insulin B15-23-reactive TRBV19(+)CD8(+) T cells and causes diabetes; 2) insulin B15-23-reactive TRBV19(+)CD8(+) T cells are more abundant in the pancreatic lymph nodes of mice lacking PI1 and/or PI2; 3) overexpression of PI2 decreases TRBV19 usage in the global CD8(+) T-cell compartment; 4) a biased repertoire of insulin-reactive CD8(+) T cells emerges in the periphery regardless of antigen exposure; and 5) low-avidity insulin-reactive CD8(+) T cells are less affected by antigen exposure in the thymus than in the periphery. These findings inform our understanding of the diabetogenic process and reveal new avenues for therapeutic exploitation in type 1 diabetes. more...

Published
2016
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31. Type 1 diabetes and pregnancy: a phenomenological study of women's first experiences

Author

Sunil Nair, Maria Woolley, Colin Jones, Frank Joseph, Usha Rao, Joanne Davies, and David Ewins

Subjects
Type 1 diabetes, Pregnancy, business.industry, Endocrinology, Diabetes and Metabolism, media_common.quotation_subject, Control (management), Attendance, Nice, medicine.disease, Action (philosophy), Nursing, Perception, Intervention (counseling), Internal Medicine, medicine, business, computer, media_common, computer.programming_language
Abstract

The aims of this study were to explore women's perceptions and experiences of being pregnant and having pre-existing type 1 diabetes mellitus, and to assess their physical, social, psychological, emotional and educational needs during their transition to motherhood. The qualitative design incorporated a purposive sample of seven women in their first pregnancy, who participated in one-to-one interviews with a researcher at 15-20 and 32-36 weeks gestation, and at 6-8 weeks post-partum. Qualitative analysis identified seven key themes from the data including: knowledge; physical and psychological impact; control and trust; catalyst to action; organisation of care and communication; attendance and intervention; expectations and systems. This study has shown that most women with diabetes who become pregnant are resigned to the fact that their pregnancy is considered high risk, and are willing to play their part to achieve a positive pregnancy outcome. However, they would also like to 'do the normal pregnant bit as well', 'normalise it and make it a nice experience' and make it feel 'less fragmented'. This woman-centred experience of pregnancy care, in women with type 1 diabetes mellitus, may motivate health professionals to revise their approach to care, prompt them to utilise the skills of each individual member of the multidisciplinary team to its full strength and potential, and assist in the provision of a positive, balanced and more holistic approach to care, specific to this client group. more...

Published
2015
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32. Adoptive transfer of mRNA-Transfected T cells redirected against diabetogenic CD8 T cells can prevent diabetes

Author

F. Susan Wong, Nathan Karin, Gideon Gross, Sigal Fishman, Joanne Davies, Alon Margalit, Evy De Leenheer, M. D. Lewis, Dimitri Kakabadse, Doron Ziv, and L. Khai Siew

Subjects
Cytotoxicity, Immunologic, 0301 basic medicine, Adoptive cell transfer, Recombinant Fusion Proteins, T-Lymphocytes, CD3, Genetic Vectors, Gene Expression, CD8-Positive T-Lymphocytes, Transfection, Major histocompatibility complex, Immunomodulation, Mice, 03 medical and health sciences, 0302 clinical medicine, Mice, Inbred NOD, Gene Order, Drug Discovery, Genetics, medicine, Animals, Insulin, Cytotoxic T cell, RNA, Messenger, Molecular Biology, NOD mice, Pharmacology, biology, T-cell receptor, medicine.disease, Adoptive Transfer, Molecular biology, Disease Models, Animal, Diabetes Mellitus, Type 1, 030104 developmental biology, Receptor-CD3 Complex, Antigen, T-Cell, biology.protein, Molecular Medicine, Female, Original Article, beta 2-Microglobulin, Insulitis, CD8, 030215 immunology
Abstract

Chimeric major histocompatibility complex (MHC) molecules supplemented with T cell receptor (TCR) signaling motifs function as activation receptors and can redirect gene-modified T cells against pathogenic CD8 T cells. We have shown that β 2 microglobulin (β 2 m) operates as a universal signaling component of MHC-I molecules when fused with the CD3-ζ chain. Linking the H-2K d -binding insulin B chain peptide insulin B chain, amino acids 15–23 (InsB 15–23 ) to the N terminus of β 2 m/CD3-ζ, redirected polyclonal CD8 T cells against pathogenic CD8 T cells in a peptide-specific manner in the non-obese diabetic (NOD) mouse. Here, we describe mRNA electroporation for delivering peptide/β 2 m/CD3-ζ genes to a reporter T cell line and purified primary mouse CD8 T cells. The peptide/β 2 m/CD3-ζ products paired with endogenous MHC-I chains and transmitted strong activation signals upon MHC-I cross-linking. The reporter T cell line transfected with InsB 15–23 /β 2 m/CD3-ζ mRNA was activated by an InsB 15–23 -H-2K d -specific CD8 T cell hybrid only when the transfected T cells expressed H-2K d . Primary NOD CD8 T cells expressing either InsB 15–23 /β 2 m/CD3-ζ or islet-specific glucose-6-phosphatase catalytic subunit-related protein, amino acids 206–214 (IGRP 206–214 )/β 2 m/CD3-ζ killed their respective autoreactive CD8 T cell targets in vitro. Furthermore, transfer of primary CD8 T cells transfected with InsB 15–23 /β 2 m/CD3-ζ mRNA significantly reduced insulitis and protected NOD mice from diabetes. Our results demonstrate that mRNA encoding chimeric MHC-I receptors can redirect effector CD8 against diabetogenic CD8 T cells, offering a new approach for the treatment of type 1 diabetes. more...

Published
2017

33. Identifying women with persistent abnormal glucose metabolism following gestational diabetes mellitus: changing times, changing populations and changing needs

Author

Joanne Davies, Victoria Photiou, Arpana Verma, Niru Goenka, Ian F. Casson, Mark Clement-Jones, and Frank Joseph

Subjects
medicine.medical_specialty, endocrine system diseases, Receiver operating characteristic, business.industry, Endocrinology, Diabetes and Metabolism, nutritional and metabolic diseases, Metabolism, Carbohydrate metabolism, medicine.disease, Impaired glucose tolerance, Gestational diabetes, Exact test, Endocrinology, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Abnormality, Cardiology and Cardiovascular Medicine, business
Abstract

Introduction: An oral glucose tolerance test (OGTT) six weeks after delivery is considered the gold standard test to identify persistently abnormal glucose metabolism in women with gestational diabetes mellitus (GDM) but the National Institute for Health and Clinical Excellence (NICE) recommends fasting plasma glucose (FPG) alone. This however, cannot be used to diagnose those with persisting impaired glucose tolerance and will also fail to identify some women with persisting diabetes mellitus (DM). This study aims to identify the percentage of women with DM and impaired glucose tolerance (IGT) that would be missed using this strategy. Methods: Data from 147 women from two sites were analysed. Fishers’ exact test was used to demonstrate differences between OGTT and FPG and a receiver operating characteristic curve was used to try and identify a FPG concentration that would predict a post-glucose load abnormality. Results: Fifty-two of the 147 women had a persistent abnormality in glucose metabolism. Twenty-three had impaired fasting glycaemia (IFG), 21 had IGT and eight women had DM. Only seven of the eight women with DM had a FPG ≥ 7.0 mmol/L and hence one out of eight women with DM (12.5%) and all 21 women with IGT would have been missed if FPG alone were used (pConclusion: Postnatal FPG alone is inadequate to identify all women with DM and would miss a significant number of women with IGT. An OGTT in all women with diagnosed GDM remains the gold standard test to identify persistent abnormal glucose metabolism in these women. more...

Published
2013
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34. Peripheral Proinsulin Expression Controls Low-Avidity Proinsulin-Reactive CD8 T Cells in Type 1 Diabetes

Author

Peter Easton, Joanne Boldison, Stephanie J. Hanna, Lai Khai Siew, James A. Pearson, Adrian Tsui, Li Wen, Terri C. Thayer, Sartaj Ahmed, F. Susan Wong, Evy De Leenheer, and Joanne Davies

Subjects
0301 basic medicine, Male, Adoptive cell transfer, Endocrinology, Diabetes and Metabolism, Mice, Transgenic, Biology, CD8-Positive T-Lymphocytes, 03 medical and health sciences, Epitopes, Mice, 0302 clinical medicine, Mice, Inbred NOD, Internal Medicine, Lymph node stromal cell, Cytotoxic T cell, Animals, Insulin, Proinsulin, NOD mice, Cell Proliferation, Mice, Knockout, Peripheral tolerance, Flow Cytometry, R1, Tolerance induction, CTL, 030104 developmental biology, Diabetes Mellitus, Type 1, 030220 oncology & carcinogenesis, Immunology, Cancer research, Female
Abstract

Low-avidity autoreactive CD8 T cells (CTLs) escape from thymic negative selection, and peripheral tolerance mechanisms are essential for their regulation. We report the role of proinsulin (PI) expression on the development and activation of insulin-specific CTLs in the NOD mouse model of type 1 diabetes. We studied insulin B-chain–specific CTL from different T-cell receptor transgenic mice (G9Cα−/−) expressing normal PI1 and PI2 or altered PI expression levels. In the absence of PI2 (Ins2−/−), CTL in pancreatic lymph nodes (PLNs) were more activated, and male G9Cα−/− mice developed T1D. Furthermore, when the insulin-specific CTLs developed in transgenic mice lacking their specific PI epitope, the CTLs demonstrated increased cytotoxicity and proliferation in vitro and in vivo in the PLNs after adoptive transfer into NOD recipients. Dendritic cell–stimulated proliferation of insulin-specific T cells was reduced in the presence of lymph node stromal cells (LNSCs) from NOD mice but not from mice lacking the PI epitope. Our study shows that LNSCs regulate CTL activation and suggests that exposure to PI in the periphery is very important in maintenance of tolerance of autoreactive T cells. This is relevant for human type 1 diabetes and has implications for the use of antigen-specific therapy in tolerance induction. more...

Published
2015

35. Improvements in thermospray flame furnace atomic absorption spectrometry

Author

Joanne Davies and Harald Berndt

Subjects
Detection limit, Chemistry, Capillary action, Analytical chemistry, Thermospray, chemistry.chemical_element, Biochemistry, Analytical Chemistry, law.invention, Nickel, Volume (thermodynamics), law, Combustor, Environmental Chemistry, Atomic absorption spectroscopy, Absorption (electromagnetic radiation), Spectroscopy
Abstract

In thermospray flame furnace atomic absorption spectrometry (TS-FF-AAS) a nickel atomization tube is placed in the acetylene/air flame on a holder built onto a standard AAS burner head. The liquid to be analyzed is transported by a low or high-pressure pump through a very hot, simple, inexpensive ceramic capillary tip acting as a flame-heated thermospray into the flame furnace. This results in complete sample introduction and increases the residence time of the sample in the absorption volume. This leads for 17 elements to a 3–110-fold improvement in the power of detection compared to conventional flame AAS. The absolute detection limits (3s values, N =25) lie between 0.2 μg l −1 (Zn) and 310 μg l −1 (Se) according to the element. The R.S.D. ( N =15) is 1.4–5.5% according to the element and applied concentration. TS-FF-AAS can easily be incorporated on any standard flame AAS instrument and can be automated with a standard autosampler. more...

Published
2003
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36. Initial steps in designing a simulation center and program to support the opening of a new women and children's hospital in Qatar

Author

Joanne Davies and Andy Davies

Subjects
Engineering, business.industry, General Medicine, Onboarding, Phase (combat), Engineering management, Patient safety, In situ simulation, Workforce, Health care, Key (cryptography), Operations management, Center (algebra and category theory), business
Abstract

Designing and building a simulation program and center is a complex endeavor. This is considerably compounded by the simultaneous planning and construction of new hospital in which it will be house. To support the opening of a new healthcare facility in Doha, Qatar, simulation was chosen as a primary educational solution for the required onboarding of an international workforce, and to help collect data on systems to ensure processes and systems are optimal for patient safety. The following article provides a high-level overview of some of the key considerations and solutions that were made to overcome the many variables that are inherent in the planning phase of designing a center and program for a new hospital. more...

Published
2015
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37. Exploring Open Spaces and Protecting Natural Places

Author

Joanne Davies

Subjects
Fence (finance), Geography, Work (electrical), Ecotourism, Tourism, Leisure and Hospitality Management, Nature Conservation, Geography, Planning and Development, Endangered species, Operations management, Environmental planning, Natural (archaeology), Tourism
Abstract

This paper explores how Australia's largest conservation volunteering organisation uses tourism as one mechanism to help protect our environment. Conservation Volunteers Australia through its range of programmes currently achieves 45,000 annual volunteer days, which is equivalent to over five million dollars worth of conservation work. The 1200 international volunteers who annually participate in a conservation holiday experience are one of the major contributors to this output. Whether it be building a 25 km fence to help save bilbies from extinction, assisting researchers to track and monitor endangered yellow footed rock wallabies, or removing litter during a coastal clean-up project, these volunteers make a considerable contribution to the enhancement of our natural environment. To expand on the current success of these tourism activities Conservation Volunteers Australia is now developing a series of ecotour programmes. The ecotours will provide a unique touring experience, while attracting a greater... more...

Published
2002
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38. 210 Clinical Utility of Gene Panel and Clinical Exome Testing in Cardiac Disease

Author

Gable, Mary, primary, Buxton, Chris, additional, Woodward, Geoff, additional, Wadsley, Marc, additional, Honeychurch, Julie, additional, Joanne, Davies, additional, Newbury-Ecob, Ruth, additional, Low, Karen, additional, Donaldson, Alan, additional, Affleck, Josphine, additional, Whittington, Rebecca, additional, Greenslade, Mark, additional, and Williams, Maggie, additional more...

Published
2016
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39. Abnormal Umbilical Artery Doppler Waveforms and Cord Blood Corticotropin-Releasing Hormone

Author

Joanne Davies, Roger Smith, Warwick B. Giles, and Mark McLean

Subjects
Adult, endocrine system, medicine.medical_specialty, Corticotropin-Releasing Hormone, Pregnancy Complications, Cardiovascular, Umbilical cord, Ultrasonography, Prenatal, Umbilical Arteries, Preeclampsia, Corticotropin-releasing hormone, Pregnancy, Internal medicine, medicine.artery, medicine, Humans, business.industry, Obstetrics and Gynecology, Umbilical artery, Blood flow, Fetal Blood, medicine.disease, Endocrinology, medicine.anatomical_structure, Fetal circulation, Cord blood, Female, business, hormones, hormone substitutes, and hormone antagonists, Hormone
Abstract

Objective To determine whether placental secretion of corticotropin-releasing hormone into the fetal circulation is increased in pregnancies complicated by umbilical-placental vascular insufficiency. Methods Twenty women with abnormal Doppler umbilical artery flow velocity waveforms and six women with uncomplicated term pregnancies and normal umbilical artery flow velocity waveforms had cord blood concentrations of corticotropin-releasing hormone, ACTH, cortisol, and β -hCG estimated. Results The mean cord blood corticotropin-releasing hormone concentration was significantly higher in pregnancies with abnormal umbilical artery flow velocity waveforms than in normal pregnancies (108 ± 27 versus 24 ± 8 pg/mL, P = .019). Elevated cord blood corticotropin-releasing hormone levels were seen in the abnormal group regardless of the presence or absence of preeclampsia or fetal growth restriction. There were no significant differences in cord blood cortisol, ACTH, or β -hCG concentrations. Conclusion The concentration of corticotropin-releasing hormone in the fetal circulation is significantly increased in pregnancies complicated by abnormal umbilical artery flow velocity waveforms. This may represent a stress-responsive compensatory mechanism in the human placenta. more...

Published
1996
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40. 4 years' cascade genetic testing for familial hypercholesterolaemia in England – Increased referrals and ascertainment

Author

Mahmoud Barbir, Carol Robinson, A. Hills, Melanie Watson, Julie Honeychurch, Maggie Williams, Graham Bayly, Nigel Wheeldon, Joanne Davies, Andrew Taylor, and J. Breen

Subjects
03 medical and health sciences, Pediatrics, medicine.medical_specialty, 0302 clinical medicine, medicine.diagnostic_test, business.industry, medicine, 030212 general & internal medicine, 030204 cardiovascular system & hematology, Cardiology and Cardiovascular Medicine, business, Genetic testing
Published
2016
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41. A taste for expat life

Author

Joanne, Davies

Subjects
Travel, Career Choice, Faculty, Nursing, Humans, Qatar, United Kingdom, Maternal-Child Nursing
Published
2012

42. Designing a patient care model with relevance to the cultural setting

Author

Donna Herrin-Griffith, Suzi Robertson-Malt, and Joanne Davies

Subjects
Patient Care Team, Medical education, medicine.medical_specialty, Academic Medical Centers, Leadership and Management, Nurse leaders, business.industry, General Medicine, Process of care, Organizational Culture, Patient care, Underdevelopment, Cultural intelligence, Family medicine, Patient-Centered Care, Health care, Medicine, Humans, Relevance (information retrieval), Cultural Competency, business, Qatar, Research center, Decision Making, Organizational
Abstract

Healthcare leaders are challenged to develop new approaches to care that better serve populations and use valuable resources in more effective and efficient ways. The authors discuss a model of care under development at Sidra Medical and Research Center, Qatar, with emphasis on how to translate the best available evidence in a way that is applicable and meaningful for the cultural setting. Strategies that nurse leaders can call upon to engage their team members' cultural intelligence during the planning and design of new processes of care are also discussed. more...

Published
2010

45. Abstract 1478: AMP-Activated Protein Kinase Phosphorylates Cardiac Troponin I and Alters Contractility in Murine Ventricular Myocytes

Author

S Marisa Oliveira, Yin-Hua Zhang, Joanne Davies, David Carling, Barbara Casadei, Hugh Watkins, and Charles Redwood

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

In the heart, AMP-activated protein kinase (AMPK) is critical in the regulation of energy balance and in myocardial signaling, and is activated especially during ischaemia and exercise. It is a αβγ heterotrimer, with α being the catalytic subunit. Mutations affecting the regulatory γ2 subunit have been shown to cause a cardiac phenotype of hypertrophy and conduction disease, thus suggesting a specific role for this subunit in the heart. The γ isoforms are highly conserved at their C-termini but very different at their N-termini; hence we have investigated whether the unique N-terminus of γ2 could be involved in conferring substrate specificity or in determining intracellular localization. We have undertaken a GAL4 -based yeast two-hybrid assay to screen a human heart cDNA library using the N-terminal 273 residues of γ2 as bait. Five proteins were identified as true interactors in the yeast assay, one of these being cardiac troponin I (cTnI). In vitro studies showed that cTnI (isolated or reconstituted as troponin complex) is a good substrate for AMPK. Studies using site-specific cTnI mutants and mass spectrometry identified Ser-150 as the principal residue phosphorylated by AMPK. Actomyosin ATPase assays showed that phosphorylation at this residue resulted in increased Ca 2+ sensitivity of contractile regulation (ΔpCa 50 =+0.07). Treatment of cardiomyocytes with the AMPK activator AICAR for 15 min resulted in prolonged relaxation (time to 50% relaxation, TR50) in field stimulated left ventricular myocytes of C57B/6 mice (TR50 in ms: 29.8±1.4 in control and 38.0±2.4 with AICAR, n=11, 3 Hz and 35 o C). There was a tendency towards an increase in contraction with AICAR. Pretreatment of myocytes with AMPK inhibitor compound C (10 μM) abolished the effects of AICAR on myocytes (TR50 in ms: 30.9±1.7 before AICAR and 31.5±2.6 after AICAR, n=9). The effect of AICAR was mediated without altering the amplitude of the Ca 2+ transient, suggesting that it may be caused by a change in myofilament Ca 2+ -sensitivity and consistent with AMPK phosphorylation of cTnI. We hypothesize that cTnI phosphorylation by AMPK may represent a novel mechanism of regulation of cardiac function. more...

Published
2007
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46. AN INTRODUCTION TO DEBRIEFING

Author

Joanne Davies

Subjects
Point (typography), Computer science, media_common.quotation_subject, Debriefing, Health Informatics, Cognition, Session (web analytics), Education, Human–computer interaction, Modeling and Simulation, Curiosity, computer, The selected best abstract submissions for the 2nd UAE Clinical Simulation Conference in collaboration with Society in Europe for Simulation Applied to Medicine, media_common, Rust (programming language), computer.programming_language
Abstract

The interactive workshop will cover the basic elements of Debriefing. Introduce a tool that can guide debriefs. Allow time for expert modelling and practice using the tools provided.Learning ObjectivesBy the end of this session participants should be able to:1. Identify the three different approaches to debriefing2. Identify the defining criteria for using the different approaches3. Describe the value of exploring participant frames4. Describe the RUST model5. Use the OPIC (Observation, Point of View, Inquiry/Curiosity) Cognitive aid to practice debriefing in the learning activityThe Sidra Sim Team would run this interactive session with 4–5 team members. more...

Published
2015
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47. Trends in physical activity participation and the impact of integrated campaigns among Australian adults, 1997-99

Author

Neville Owen, Bill Bellew, Joanne Davies, Tim Armstrong, Adrian Bauman, Philip Vita, and Wendy J. Brown

Subjects
Strategic planning, Adult, Male, medicine.medical_specialty, Health Knowledge, Attitudes, Practice, lcsh:Public aspects of medicine, Public health, Public Health, Environmental and Occupational Health, Physical activity, Australia, lcsh:RA1-1270, Moderate activity, Health Promotion, Middle Aged, Political science, Environmental health, medicine, Humans, Female, Public education, Exercise, Aged
Abstract

Objectives: To determine whether awareness of the moderate physical activity message and prevalence of participation changed among Australian adults between 1997 and 1999, and if changes differed across Australia. Methods: Data were compared on awareness of the moderate physical activity message and on physical activity participation from identical national physical activity surveys in 1997 and 1999. Results: In 1999, following integrated public health efforts, recognition of the Active Australia campaign was substantially higher in NSW/ACT (61.7%) than elsewhere (29.3%). Knowledge about benefits of moderate activity increased between 1997 and 1999, more so in States with public health campaigns. National participation in ‘sufficient physical activity’ declined between 1997 and 1999, from 63% to 57%, but the decline was smaller in NSW/ACT (4.4%) than in the other States (6.0%). Conclusions and implications: Declining trends in physical activity in Australia require increased public health investments, including strategic planning and public education, such as occurred in NSW (1997/98). more...

Published
2004

48. Renal excretion of 8-oxo-7,8-dihydro-2(')-deoxyguanosine: degradation rates of RNA and metabolic rate in humans

Author

Willibald Stichler, Heinrich Topp, Christoph Lengger, Gerhard Schöch, Joanne Davies, Friedrich Manz, Sven Armbrust, and Christoph Fusch

Subjects
Adult, Male, medicine.medical_specialty, Biophysics, Kidney, Biochemistry, Excretion, Absorptiometry, Photon, RNA, Transfer, Internal medicine, medicine, Humans, Child, Molecular Biology, chemistry.chemical_classification, Reactive oxygen species, RNA, Deoxyguanosine, Calorimetry, Indirect, Ribosomal RNA, Oxidative Stress, Endocrinology, chemistry, 8-Hydroxy-2'-Deoxyguanosine, RNA, Ribosomal, Renal physiology, Basal metabolic rate, Lean body mass, Female, Basal Metabolism, Densitometry, Energy Metabolism, Reactive Oxygen Species, DNA Damage
Abstract

Renally excreted 8-oxo-7,8-dihydro-2(')-deoxyguanosine (oxo(8)dG) is a potential marker of oxidative DNA damage by reactive oxygen species. Whole-body degradation rates of t- and rRNA are potential indicators of the resting metabolic rate (RMR). Excretion rates of oxo(8)dG and degradation rates of t- and rRNA were determined in healthy non-smoking adults and children. RMR (indirect calorimetry; 14 children, 16 adults), total energy expenditure (TEE; doubly labelled water technique; 4 children, 6 adults), and lean body mass (LBM; dual-energy X-ray absorptiometry; 14 children, 16 adults) were also measured. Degradation of t- and rRNA (micromol/d/kg LBM; 4 children, 6 adults) was highly correlated with RMR (kJ/d/kg LBM), r=0.867 (p0.005) and 0.959 (p0.001), respectively. Excretion of oxo(8)dG (pmol/d/kg LBM; 14 children, 16 adults) was not significantly correlated with RMR (p0.05). Neither excretion of oxo(8)dG nor degradation of RNA was significantly correlated with TEE (kJ/d/ kg LBM) (p0.05). In healthy subjects further factors, other than the metabolic rate, seem to influence the excretion rate of oxo(8)dG. The degradation rates of t- and rRNA seem to be appropriate indicators of the RMR. more...

Published
2002

49. Corticotropin-releasing hormone in chimpanzee and gorilla pregnancies

Author

Anne Belleoud, Roger Smith, Joanne Davies, Guy Dubreuil, E. Jean Wickings, Maria Bowman, and Gemma Madsen

Subjects
endocrine system, medicine.medical_specialty, Corticorelin, Hydrocortisone, Pan troglodytes, medicine.drug_class, Corticotropin-Releasing Hormone, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Gorilla, Biochemistry, Corticotropin-releasing hormone, chemistry.chemical_compound, Endocrinology, Dehydroepiandrosterone sulfate, Pregnancy, Internal medicine, biology.animal, Blood plasma, polycyclic compounds, medicine, Animals, Progesterone, Gorilla gorilla, biology, Estradiol, Dehydroepiandrosterone Sulfate, Biochemistry (medical), Myometrium, Androgen, nervous system, chemistry, Estrogen, Pregnancy, Animal, Female, Carrier Proteins, hormones, hormone substitutes, and hormone antagonists
Abstract

In humans, the length of gestation and the onset of parturition have been linked to the exponential production of placental CRH and a late gestational decline in maternal plasma CRH-binding protein (CRH-BP). CRH has been shown to have direct effects on the myometrium and on the fetal adrenal, where it stimulates production of the estrogen precursor dihydroepiandrosterone sulfate. In vitro placental CRH production is stimulated by cortisol and inhibited by progesterone. To determine whether this mechanism might operate in other apes, we sampled eight chimpanzees and two gorillas through their pregnancies for CRH, CRH-BP, cortisol, estradiol, progesterone, and a-fetoprotein. We show that both chimpanzee and gorilla maternal plasma CRH concentrations rise exponentially as observed in the human. The gorillas exhibited a human-like antepartum fall in CRH-BP, whereas CRH-BP in the chimpanzee remained stable. Pregnancy-associated changes in cortisol, estradiol, progesterone, and a-fetoprotein were qualitatively similar to those observed in humans. Maternal plasma cortisol correlated with plasma CRH in both gorillas (r 5 0.60; P , 0.05) and chimpanzees (r 5 0.36; P , 0.02). Further, there was a strong correlation between plasma estradiol and the log of plasma CRH in the gorilla (r 5 0.93; P , 0.0001) and in the chimpanzee (r 5 0.72; P , 0.001), which is consistent with the hypothesis that placental CRH determines the placental production of estradiol by stimulating the production of fetal adrenal dehydroepiandrosterone sulfate. Plasma CRH and progesterone were positively correlated providing no in vivo support for progesterone inhibition of CRH release. (J Clin Endocrinol Metab 84: 2820 ‐2825, 1999) more...

Published
1999

50. Predicting risk of preterm delivery by second-trimester measurement of maternal plasma corticotropin-releasing hormone and alpha-fetoprotein concentrations

Author

Mark McLean, Allan Hackshaw, Roger Smith, Kerry De Voss, Joanne Davies, W.A.W. Walters, and Andrew Bisits

Subjects
Adult, medicine.medical_specialty, Adolescent, Corticotropin-Releasing Hormone, Radioimmunoassay, Corticotropin-releasing hormone, Obstetric Labor, Premature, Predictive Value of Tests, Pregnancy, Risk Factors, medicine, Odds Ratio, Humans, Prospective Studies, Risk factor, Gynecology, business.industry, Obstetrics and Gynecology, Odds ratio, medicine.disease, Risk Estimate, Predictive value of tests, Pregnancy Trimester, Second, Gestation, Female, alpha-Fetoproteins, Risk assessment, business, Biomarkers
Abstract

Many women who have preterm labor have abnormally high plasma concentrations of the placental peptide corticotropin-releasing hormone and the fetal product alpha-fetoprotein in early pregnancy. This study was designed to evaluate the ability of these biochemical tests and a clinical risk factor score to prospectively discriminate pregnancies at high risk for preterm delivery.Eight hundred sixty women were studied prospectively from the early second trimester until delivery. A risk factor score for preterm delivery was calculated from the clinical history and maternal plasma corticotropin-releasing hormone and alpha-fetoprotein concentrations were measured by radioimmunoassay between 17 and 30 weeks' gestation. The risk factor score, corticotropin-releasing hormone concentration, and alpha-fetoprotein concentration for each woman were expressed as individual odds or likelihood ratios for preterm delivery and as a combined risk estimate derived from the 3 tests.Sixty women had preterm deliveries (n = 37 spontaneous labor, n = 23 planned deliveries), and these women had significantly higher concentrations of corticotropin-releasing hormone (median 1.92 multiples of the median) and alpha-fetoprotein (median 1.32 multiples of the median) than did women with term deliveries (median 1.00 multiples of the median, P.001 for both tests), with these abnormalities being evident from early in the second trimester. The risk factor score was/=10 in 28% of women with preterm delivery and 7% of women with term delivery. The combination of all 3 markers resulted in a higher detection rate and a higher positive predictive value than the risk factor score, corticotropin-releasing hormone concentration, or alpha-fetoprotein concentration alone, correctly discriminating 37% of women who would have preterm deliveries with a false-positive rate of 5%. The positive predictive value was also 37% (odds of being affected given a positive result were 1:1.7).The combination of measurement of maternal plasma corticotropin-releasing hormone and alpha-fetoprotein concentrations in the second trimester with risk factor scoring provides a more accurate indicator of the risk of preterm delivery than does risk factor scoring alone. This method of risk assessment may therefore be of use in targeting prevention strategies. more...

Published
1999