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1. Bacille Calmette-Guérin vaccination to prevent febrile and respiratory illness in adults (BRACE): secondary outcomes of a randomised controlled phase 3 trialResearch in context

Author

Laure F. Pittet, Nicole L. Messina, Ellie McDonald, Francesca Orsini, Simone Barry, Marc Bonten, John Campbell, Julio Croda, Mariana G. Croda, Margareth Dalcolmo, Kaya Gardiner, Amanda Gwee, Bruno Jardim, Marcus V.G. Lacerda, Michaela Lucas, David J. Lynn, Laurens Manning, Kirsten P. Perrett, Jeffrey J. Post, Cristina Prat-Aymerich, Peter C. Richmond, Jorge L. Rocha, Jesus Rodriguez-Baño, Adilia Warris, Nicholas J. Wood, Andrew Davidson, Nigel Curtis, Tenaya Jamieson, Nicole Messina, Thilanka Morawakage, Susan Perlen, Kirsten Perrett, Laure Pittet, Amber Sastry, Jia Wei Teo, Katherine Lee, Cecilia Moore, Suzanna Vidmar, Rashida Ali, Ross Dunn, Peta Edler, Grace Gell, Casey Goodall, Richard Hall, Ann Krastev, Nathan La, Nick McPhate, Thao Nguyen, Jack Ren, Luke Stevens, Ahmed Alamrousi, Rhian Bonnici, Thanh Dang, Susie Germano, Jenny Hua, Rebecca McElroy, Monica Razmovska, Scott Reddiex, Xiaofang Wang, Jeremy Anderson, Kristy Azzopardi, Vicki Bennett-Wood, Anna Czajko, Nadia Mazarakis, Conor McCafferty, Frances Oppedisano, Belinda Ortika, Casey Pell, Leena Spry, Ryan Toh, Sunitha Velagapudi, Amanda Vlahos, Ashleigh Wee-Hee, Pedro Ramos, Karina De La Cruz, Dinusha Gamage, Anushka Karunanayake, Isabella Mezzetti, Benjamin Ong, Ronita Singh, Enoshini Sooriyarachchi, Suellen Nicholson, Natalie Cain, Rianne Brizuela, Han Huang, Veronica Abruzzo, Morgan Bealing, Patricia Bimboese, Kirsty Bowes, Emma Burrell, Joyce Chan, Jac Cushnahan, Hannah Elborough, Olivia Elkington, Kieran Fahey, Monique Fernandez, Catherine Flynn, Sarah Fowler, Marie Gentile Andrit, Bojana Gladanac, Catherine Hammond, Norine Ma, Sam Macalister, Emmah Milojevic, Jesutofunmi Mojeed, Jill Nguyen, Liz O'Donnell, Nadia Olivier, Isabelle Ooi, Stephanie Reynolds, Lisa Shen, Barb Sherry, Judith Spotswood, Jamie Wedderburn, Angela Younes, Donna Legge, Jason Bell, Jo Cheah, Annie Cobbledick, Kee Lim, Sonja Elia, Lynne Addlem, Anna Bourke, Clare Brophy, Nadine Henare, Narelle Jenkins, Francesca Machingaifa, Skye Miller, Kirsten Mitchell, Sigrid Pitkin, Kate Wall, Paola Villanueva, Nigel Crawford, Wendy Norton, Niki Tan, Thilakavathi Chengodu, Diane Dawson, Victoria Gordon, Tony Korman, Jess O'Bryan, Sophie Agius, Samantha Bannister, Jess Bucholc, Alison Burns, Beatriz Camesella, John Carlin, Marianna Ciaverella, Maxwell Curtis, Stephanie Firth, Christina Guo, Matthew Hannan, Erin Hill, Sri Joshi, Katherine Lieschke, Megan Mathers, Sasha Odoi, Ashleigh Rak, Chris Richards, Leah Steve, Carolyn Stewart, Eva Sudbury, Helen Thomson, Emma Watts, Fiona Williams, Angela Young, Penny Glenn, Andrew Kaynes, Amandine Philippart De Floy, Sandy Buchanan, Thijs Sondag, Ivy Xie, Harriet Edmund, Bridie Byrne, Tom Keeble, Belle Ngien, Fran Noonan, Michelle Wearing-Smith, Alison Clarke, Pemma Davies, Oliver Eastwood, Alric Ellinghaus, Rachid Ghieh, Zahra Hilton, Emma Jennings, Athina Kakkos, Iris Liang, Katie Nicol, Sally O'Callaghan, Helen Osman, Gowri Rajaram, Sophia Ratcliffe, Victoria Rayner, Ashleigh Salmon, Angela Scheppokat, Aimee Stevens, Rebekah Street, Nicholas Toogood, Nicholas Wood, Twinkle Bahaduri, Therese Baulman, Jennifer Byrne, Candace Carter, Mary Corbett, Aiken Dao, Maria Desylva, Andrew Dunn, Evangeline Gardiner, Rosemary Joyce, Rama Kandasamy, Craig Munns, Lisa Pelayo, Ketaki Sharma, Katrina Sterling, Caitlin Uren, Clinton Colaco, Mark Douglas, Kate Hamilton, Adam Bartlett, Brendan McMullan, Pamela Palasanthiran, Phoebe Williams, Justin Beardsley, Nikki Bergant, Renier Lagunday, Kristen Overton, Jeffrey Post, Yasmeen Al-Hindawi, Sarah Barney, Anthony Byrne, Lee Mead, Marshall Plit, David Lynn, Saoirse Benson, Stephen Blake, Rochelle Botten, Tee Yee Chern, Georgina Eden, Liddy Griffith, Jane James, Miriam Lynn, Angela Markow, Domenic Sacca, Natalie Stevens, Steve Wesselingh, Catriona Doran, Alice Sawka, Sue Evans, Louise Goodchild, Christine Heath, Meredith Krieg, Helen Marshall, Mark McMillan, Mary Walker, Peter Richmond, Nelly Amenyogbe, Christina Anthony, Annabelle Arnold, Beth Arrowsmith, Rym Ben-Othman, Sharon Clark, Jemma Dunnill, Nat Eiffler, Krist Ewe, Carolyn Finucane, Lorraine Flynn, Camille Gibson, Lucy Hartnell, Elysia Hollams, Heidi Hutton, Lance Jarvis, Jane Jones, Jan Jones, Karen Jones, Jennifer Kent, Tobias Kollmann, Debbie Lalich, Wenna Lee, Rachel Lim, Sonia McAlister, Fiona McDonald, Andrea Meehan, Asma Minhaj, Lisa Montgomery, Melissa O'Donnell, Jaslyn Ong, Joanne Ong, Kimberley Parkin, Glady Perez, Catherine Power, Shadie Rezazadeh, Holly Richmond, Sally Rogers, Nikki Schultz, Margaret Shave, Patrycja Skut, Lisa Stiglmayer, Alexandra Truelove, Ushma Wadia, Rachael Wallace, Justin Waring, Michelle England, Erin Latkovic, Susan Herrmann, Marcus Lacerda, Paulo Henrique Andrade, Fabiane Bianca Barbosa, Dayanne Barros, Larissa Brasil, Ana Greyce Capella, Ramon Castro, Erlane Costa, Dilcimar de Souza, Maianne Dias, José Dias, Klenilson Ferreira, Paula Figueiredo, Thamires Freitas, Ana Carolina Furtado, Larissa Gama, Vanessa Godinho, Cintia Gouy, Daniele Hinojosa, Tyane Jardim, Joel Junior, Augustto Lima, Bernardo Maia, Adriana Marins, Kelry Mazurega, Tercilene Medeiros, Rosangela Melo, Marinete Moraes, Elizandra Nascimento, Juliana Neves, Maria Gabriela Oliveira, Thais Oliveira, Ingrid Oliveira, Arthur Otsuka, Rayssa Paes, Handerson Pereira, Gabrielle Pereira, Christiane Prado, Evelyn Queiroz, Laleyska Rodrigues, Bebeto Rodrigues, Vanderson Sampaio, Anna Gabriela Santos, Daniel Santos, Tilza Santos, Evelyn Santos, Ariandra Sartim, Ana Beatriz Silva, Juliana Silva, Emanuelle Silva, Mariana Simão, Caroline Soares, Antonny Sousa, Alexandre Trindade, Fernando Val, Adria Vasconcelos, Heline Vasconcelos, Carolinne Abreu, Katya Martinez Almeida, Camila Bitencourt de Andrade, Jhenyfer Thalyta Campos Angelo, Ghislaine Gonçalvez de Araújo Arcanjo, Bianca Maria Silva Menezes Arruda, Wellyngthon Espindola Ayala, Adelita Agripina Refosco Barbosa, Felipe Zampieri Vieira Batista, Fabiani de Morais Batista, Miriam de Jesus Costa, Mariana Garcia Croda, Lais Alves da Cruz, Roberta Carolina Pereira Diogo, Rodrigo Cezar Dutra Escobar, Iara Rodrigues Fernandes, Leticia Ramires Figueiredo, Leandro Galdino Cavalcanti Gonçalves, Sarita Lahdo, Joyce dos Santos Lencina, Guilherme Teodoro de Lima, Bruna Tayara LEOPOLDINA MEIRELES, Debora Quadros Moreira, Lilian Batista Silva Muranaka, Adriely de Oliveira, Karla Regina Warszawski de Oliveira, Matheus Vieira de Oliveira, Roberto Dias de Oliveira, Andrea Antonia Souza de Almeida dos Reis Pereira, Marco Puga, Caroliny Veron Ramos, Thaynara Haynara Souza da Rosa, Karla Lopes dos Santos, Claudinalva Ribeiro dos Santos, Dyenyffer Stéffany Leopoldina dos Santos, Karina Marques Santos, Paulo César Pereira da Silva, Paulo Victor Rocha da Silva, Débora dos Santos Silva, Patricia Vieira da Silva, Bruno Freitas da Rosa Soares, Mariana Gazzoni Sperotto, Mariana Mayumi Tadokoro, Daniel Tsuha, Hugo Miguel Ramos Vieira, Margareth Maria Pretti Dalcolmo, Cíntia Maria Lopes Alves da Paixão, Gabriela Corrêa E Castro, Simone Silva Collopy, Renato da Costa Silva, Samyra Almeida da Silveira, Alda Maria Da-Cruz, Alessandra Maria da Silva Passos de Carvalho, Rita de Cássia Batista, Maria Luciana Silva De Freitas, Aline Gerhardt de Oliveira Ferreira, Ana Paula Conceição de Souza, Paola Cerbino Doblas, Ayla Alcoforado da Silva dos Santos, Vanessa Cristine de Moraes dos Santos, Dayane Alves dos Santos Gomes, Anderson Lage Fortunato, Adriano Gomes-Silva, Monique Pinto Gonçalves, Paulo Leandro Garcia Meireless Junior, Estela Martins da Costa Carvalho, Fernando do Couto Motta, Ligia Maria Olivo de Mendonça, Girlene dos Santos Pandine, Rosa Maria Plácido Pereira, Ivan Ramos Maia, Jorge Luiz da Rocha, João Victor Paiva Romano, Glauce dos Santos, Erica Fernandes da Silva, Marilda Agudo Mendonça Teixeira de Siqueira, Ágatha Cristinne Prudêncio Soares, Sandra Franch Arroyo, Henny Ophorst-den Besten, Anna Boon, Karin M. Brakke, Axel Janssen, Marijke A.H. Koopmans, Toos Lemmens, Titia Leurink, Engelien Septer-Bijleveld, Kimberly Stadhouders, Darren Troeman, Marije van der Waal, Marjoleine van Opdorp, Nicolette van Sluis, Beatrijs Wolters, Jan Kluytmans, Jannie Romme, Wouter van den Bijllaardt, Linda van Mook, M.M.L (Miranda) van Rijen, P.M.G. Filius, Jet Gisolf, Frances Greven, Danique Huijbens, Robert Jan Hassing, R.C. Pon, Lieke Preijers, J.H. van Leusen, Harald Verheij, Wim Boersma, Evelien Brans, Paul Kloeg, Kitty Molenaar-Groot, Nhat Khanh Nguyen, Nienke Paternotte, Anke Rol, Lida Stooper, Helga Dijkstra, Esther Eggenhuizen, Lucas Huijs, Simone Moorlag, Mihai Netea, Eva Pranger, Esther Taks, Jaap ten Oever, Rob ter Heine, Kitty Blauwendraat, Bob Meek, Isil Erkaya, Houda Harbech, Nienke Roescher, Rifka Peeters, Menno te Riele, Carmen Zhou, Esther Calbo, Cristina Badia Marti, Emma Triviño Palomares, Tomás Perez Porcuna, Anabel Barriocanal, Ana Maria Barriocanal, Irma Casas, Jose Dominguez, Maria Esteve, Alicia Lacoma, Irene Latorre, Gemma Molina, Barbara Molina, Antoni Rosell, Sandra Vidal, Lydia Barrera, Natalia Bustos, Ines Portillo Calderón, David Gutierrez Campos, Jose Manuel Carretero, Angel Dominguez Castellano, Renato Compagnone, Encarnacion Ramirez de Arellano, Almudena de la Serna, Maria Dolores del Toro Lopez, Marie-Alix Clement Espindola, Ana Belen Martin Gutierrez, Alvaro Pascual Hernandez, Virginia Palomo Jiménez, Elisa Moreno, Nicolas Navarrete, Teresa Rodriguez Paño, Jesús Rodríguez-Baño, Enriqueta Tristán, Maria Jose Rios Villegas, Atsegiñe Canga Garces, Erika Castro Amo, Raquel Coya Guerrero, Josune Goikoetxea, Leticia Jorge, Cristina Perez, María Carmen Fariñas Álvarez, Manuel Gutierrez Cuadra, Francisco Arnaiz de las Revillas Almajano, Pilar Bohedo Garcia, Teresa Giménez Poderos, Claudia González Rico, Blanca Sanchez, Olga Valero, Noelia Vega, Anna Barnes, Helen Catterick, Tim Cranston, Phoebe Dawe, Emily Fletcher, Liam Fouracre, Alison Gifford, Neil Gow, John Kirkwood, Christopher Martin, Amy McAnew, Marcus Mitchell, Georgina Newman, Abby O'Connell, Jakob Onysk, Lynne Quinn, Shelley Rhodes, Samuel Stone, Lorrie Symons, Harry Tripp, Darcy Watkins, Bethany Whale, Alex Harding, Gemma Lockhart, Kate Sidaway-Lee, Sam Hilton, Sarah Manton, Daniel Webber-Rookes, Rachel Winder, James Moore, Freya Bateman, Michael Gibbons, Bridget Knight, Julie Moss, Sarah Statton, Josephine Studham, Lydia Hall, Will Moyle, and Tamsin Venton

Subjects
Bacille Calmette-Guérin (BCG) vaccine, Immunity, Heterologous, Health personnel, Randomised controlled trial, Primary prevention, Medicine (General), R5-920
Abstract

Summary: Background: Bacille Calmette-Guérin (BCG) vaccination has off-target (non-specific) effects that are associated with protection against unrelated infections and decreased all-cause mortality in infants. We aimed to determine whether BCG vaccination prevents febrile and respiratory infections in adults. Methods: This randomised controlled phase 3 trial was done in 36 healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom. Healthcare workers were randomised to receive BCG-Denmark (single 0.1 ml intradermal injection) or no BCG in a 1:1 ratio using a web-based procedure, stratified by stage, site, age, and presence of co-morbidity. The difference in occurrence of febrile or respiratory illness were measured over 12 months (prespecified secondary outcome) using the intention-to-treat (ITT) population. This trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020, and April 1, 2021, 6828 healthcare workers were randomised to BCG-Denmark (n = 3417) or control (n = 3411; no intervention or placebo) groups. The 12-month adjusted estimated risk of ≥1 episode of febrile or respiratory illness was 66.8% in the BCG group (95% CI 65.3%–68.2%), compared with 63.4% in the control group (95% CI 61.8%–65.0%), a difference of +3.4 percentage points (95% CI +1.3% to +5.5%; p 0.002). The adjusted estimated risk of a severe episode (defined as being incapacitated for ≥3 consecutive days or hospitalised) was 19.4% in the BCG group (95% CI 18.0%–20.7%), compared with 18.8% in the control group (95% CI 17.4%–20.2%) a difference of +0.6 percentage points (95% CI −1.3% to +2.5%; p 0.6). Both groups had a similar number of episodes of illness, pneumonia, and hospitalisation. There were three deaths, all in the control group. There were no safety concerns following BCG vaccination. Interpretation: In contrast to the beneficial off-target effects reported following neonatal BCG in infants, a small increased risk of symptomatic febrile or respiratory illness was observed in the 12 months following BCG vaccination in adults. There was no evidence of a difference in the risk of severe disease. Funding: Bill & Melinda Gates Foundation, Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, the National Health and Medical Research Council, the Swiss National Science Foundation and individual donors.

Published
2024
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2. Specific and off-target immune responses following COVID-19 vaccination with ChAdOx1-S and BNT162b2 vaccines—an exploratory sub-study of the BRACE trialResearch in context

Author

Nicole L. Messina, Susie Germano, Rebecca McElroy, Rhian Bonnici, Branka Grubor-Bauk, David J. Lynn, Ellie McDonald, Suellen Nicholson, Kirsten P. Perrett, Laure F. Pittet, Rajeev Rudraraju, Natalie E. Stevens, Kanta Subbarao, Nigel Curtis, Andrew Davidson, Kaya Gardiner, Amanda Gwee, Tenaya Jamieson, Nicole Messina, Thilanka Morawakage, Susan Perlen, Kirsten Perrett, Laure Pittet, Amber Sastry, Jia Wei Teo, Francesca Orsini, Katherine Lee, Cecilia Moore, Suzanna Vidmar, Rashida Ali, Ross Dunn, Peta Edler, Grace Gell, Casey Goodall, Richard Hall, Ann Krastev, Nathan La, Nick McPhate, Thao Nguyen, Jack Ren, Luke Stevens, Ahmed Alamrousi, Thanh Dang, Jenny Hua, Monica Razmovska, Scott Reddiex, Xiaofang Wang, Jeremy Anderson, Kristy Azzopardi, Vicki Bennett-Wood, Anna Czajko, Nadia Mazarakis, Conor McCafferty, Frances Oppedisano, Belinda Ortika, Casey Pell, Leena Spry, Ryan Toh, Sunitha Velagapudi, Amanda Vlahos, Ashleigh Wee-Hee, Pedro Ramos, Karina De La Cruz, Dinusha Gamage, Anushka Karunanayake, Isabella Mezzetti, Benjamin Ong, Ronita Singh, Enoshini Sooriyarachchi, Natalie Cain, Rianne Brizuela, Han Huang, Veronica Abruzzo, Morgan Bealing, Patricia Bimboese, Kirsty Bowes, Emma Burrell, Joyce Chan, Jac Cushnahan, Hannah Elborough, Olivia Elkington, Kieran Fahey, Monique Fernandez, Catherine Flynn, Sarah Fowler, Marie Gentile Andrit, Bojana Gladanac, Catherine Hammond, Norine Ma, Sam Macalister, Emmah Milojevic, Jesutofunmi Mojeed, Jill Nguyen, Liz O’Donnell, Nadia Olivier, Isabelle Ooi, Stephanie Reynolds, Lisa Shen, Barb Sherry, Judith Spotswood, Jamie Wedderburn, Angela Younes, Donna Legge, Jason Bell, Jo Cheah, Annie Cobbledick, Kee Lim, Sonja Elia, Lynne Addlem, Anna Bourke, Clare Brophy, Nadine Henare, Narelle Jenkins, Francesca Machingaifa, Skye Miller, Kirsten Mitchell, Sigrid Pitkin, Kate Wall, Paola Villanueva, Nigel Crawford, Wendy Norton, Niki Tan, Thilakavathi Chengodu, Diane Dawson, Victoria Gordon, Tony Korman, Jess O’Bryan, Sophie Agius, Samantha Bannister, Jess Bucholc, Alison Burns, Beatriz Camesella, John Carlin, Marianna Ciaverella, Maxwell Curtis, Stephanie Firth, Christina Guo, Matthew Hannan, Erin Hill, Sri Joshi, Katherine Lieschke, Megan Mathers, Sasha Odoi, Ashleigh Rak, Chris Richards, Leah Steve, Carolyn Stewart, Eva Sudbury, Helen Thomson, Emma Watts, Fiona Williams, Angela Young, Penny Glenn, Andrew Kaynes, Amandine Philippart De Floy, Sandy Buchanan, Thijs Sondag, Ivy Xie, Harriet Edmund, Bridie Byrne, Tom Keeble, Belle Ngien, Fran Noonan, Michelle Wearing-Smith, Alison Clarke, Pemma Davies, Oliver Eastwood, Alric Ellinghaus, Rachid Ghieh, Zahra Hilton, Emma Jennings, Athina Kakkos, Iris Liang, Katie Nicol, Sally O’Callaghan, Helen Osman, Gowri Rajaram, Sophia Ratcliffe, Victoria Rayner, Ashleigh Salmon, Angela Scheppokat, Aimee Stevens, Rebekah Street, Nicholas Toogood, Nicholas Wood, Twinkle Bahaduri, Therese Baulman, Jennifer Byrne, Candace Carter, Mary Corbett, Aiken Dao, Maria Desylva, Andrew Dunn, Evangeline Gardiner, Rosemary Joyce, Rama Kandasamy, Craig Munns, Lisa Pelayo, Ketaki Sharma, Katrina Sterling, Caitlin Uren, Clinton Colaco, Mark Douglas, Kate Hamilton, Adam Bartlett, Brendan McMullan, Pamela Palasanthiran, Phoebe Williams, Justin Beardsley, Nikki Bergant, Renier Lagunday, Kristen Overton, Jeffrey Post, Yasmeen Al-Hindawi, Sarah Barney, Anthony Byrne, Lee Mead, Marshall Plit, David Lynn, Saoirse Benson, Stephen Blake, Rochelle Botten, Tee Yee Chern, Georgina Eden, Liddy Griffith, Jane James, Miriam Lynn, Angela Markow, Domenic Sacca, Natalie Stevens, Steve Wesselingh, Catriona Doran, Simone Barry, Alice Sawka, Sue Evans, Louise Goodchild, Christine Heath, Meredith Krieg, Helen Marshall, Mark McMillan, Mary Walker, Peter Richmond, Nelly Amenyogbe, Christina Anthony, Annabelle Arnold, Beth Arrowsmith, Rym Ben-Othman, Sharon Clark, Jemma Dunnill, Nat Eiffler, Krist Ewe, Carolyn Finucane, Lorraine Flynn, Camille Gibson, Lucy Hartnell, Elysia Hollams, Heidi Hutton, Lance Jarvis, Jane Jones, Jan Jones, Karen Jones, Jennifer Kent, Tobias Kollmann, Debbie Lalich, Wenna Lee, Rachel Lim, Sonia McAlister, Fiona McDonald, Andrea Meehan, Asma Minhaj, Lisa Montgomery, Melissa O’Donnell, Jaslyn Ong, Joanne Ong, Kimberley Parkin, Glady Perez, Catherine Power, Shadie Rezazadeh, Holly Richmond, Sally Rogers, Nikki Schultz, Margaret Shave, Patrycja Skut, Lisa Stiglmayer, Alexandra Truelove, Ushma Wadia, Rachael Wallace, Justin Waring, Michelle England, Erin Latkovic, Laurens Manning, Susan Herrmann, Michaela Lucas, Marcus Lacerda, Paulo Henrique Andrade, Fabiane Bianca Barbosa, Dayanne Barros, Larissa Brasil, Ana Greyce Capella, Ramon Castro, Erlane Costa, Dilcimar de Souza, Maianne Dias, José Dias, Klenilson Ferreira, Paula Figueiredo, Thamires Freitas, Ana Carolina Furtado, Larissa Gama, Vanessa Godinho, Cintia Gouy, Daniele Hinojosa, Bruno Jardim, Tyane Jardim, Joel Junior, Augustto Lima, Bernardo Maia, Adriana Marins, Kelry Mazurega, Tercilene Medeiros, Rosangela Melo, Marinete Moraes, Elizandra Nascimento, Juliana Neves, Maria Gabriela Oliveira, Thais Oliveira, Ingrid Oliveira, Arthur Otsuka, Rayssa Paes, Handerson Pereira, Gabrielle Pereira, Christiane Prado, Evelyn Queiroz, Laleyska Rodrigues, Bebeto Rodrigues, Vanderson Sampaio, Anna Gabriela Santos, Daniel Santos, Tilza Santos, Evelyn Santos, Ariandra Sartim, Ana Beatriz Silva, Juliana Silva, Emanuelle Silva, Mariana Simão, Caroline Soares, Antonny Sousa, Alexandre Trindade, Fernando Val, Adria Vasconcelos, Heline Vasconcelos, Julio Croda, Carolinne Abreu, Katya Martinez Almeida, Camila Bitencourt de Andrade, Jhenyfer Thalyta Campos Angelo, Ghislaine Gonçalvez de Araújo Arcanjo, Bianca Maria Silva Menezes Arruda, Wellyngthon Espindola Ayala, Adelita Agripina Refosco Barbosa, Felipe Zampieri Vieira Batista, Fabiani de Morais Batista, Miriam de Jesus Costa, Mariana Garcia Croda, Lais Alves da Cruz, Roberta Carolina Pereira Diogo, Rodrigo Cezar Dutra Escobar, Iara Rodrigues Fernandes, Leticia Ramires Figueiredo, Leandro Galdino Cavalcanti Gonçalves, Sarita Lahdo, Joyce dos Santos Lencina, Guilherme Teodoro de Lima, Larissa Santos Matos, Bruna Tayara Leopoldina Meireles, Debora Quadros Moreira, Lilian Batista Silva Muranaka, Adriely de Oliveira, Karla Regina Warszawski de Oliveira, Matheus Vieira de Oliveira, Roberto Dias de Oliveira, Andrea Antonia Souza de Almeida dos Reis Pereira, Marco Puga, Caroliny Veron Ramos, Thaynara Haynara Souza da Rosa, Karla Lopes dos Santos, Claudinalva Ribeiro dos Santos, Dyenyffer Stéffany Leopoldina dos Santos, Karina Marques Santos, Paulo César Pereira da Silva, Paulo Victor Rocha da Silva, Débora dos Santos Silva, Patricia Vieira da Silva, Bruno Freitas da Rosa Soares, Mariana Gazzoni Sperotto, Mariana Mayumi Tadokoro, Daniel Tsuha, Hugo Miguel Ramos Vieira, Margareth Maria Pretti Dalcolmo, Cíntia Maria Lopes Alves da Paixão, Gabriela Corrêa E Castro, Simone Silva Collopy, Renato da Costa Silva, Samyra Almeida da Silveira, Alda Maria Da-Cruz, Alessandra Maria da Silva Passos de Carvalho, Rita de Cássia Batista, Maria Luciana Silva De Freitas, Aline Gerhardt de Oliveira Ferreira, Ana Paula Conceição de Souza, Paola Cerbino Doblas, Ayla Alcoforado da Silva dos Santos, Vanessa Cristine de Moraes dos Santos, Dayane Alves dos Santos Gomes, Anderson Lage Fortunato, Adriano Gomes-Silva, Monique Pinto Gonçalves, Paulo Leandro Garcia Meireless Junior, Estela Martins da Costa Carvalho, Fernando do Couto Motta, Ligia Maria Olivo de Mendonça, Girlene dos Santos Pandine, Rosa Maria Plácido Pereira, Ivan Ramos Maia, Jorge Luiz da Rocha, João Victor Paiva Romano, Glauce dos Santos, Erica Fernandes da Silva, Marilda Agudo Mendonça Teixeira de Siqueira, Ágatha Cristinne Prudêncio Soares, Marc Bonten, Sandra Franch Arroyo, Henny Ophorst-den Besten, Anna Boon, Karin M. Brakke, Axel Janssen, Marijke A.H. Koopmans, Toos Lemmens, Titia Leurink, Cristina Prat-Aymerich, Engelien Septer-Bijleveld, Kimberly Stadhouders, Darren Troeman, Marije van der Waal, Marjoleine van Opdorp, Nicolette van Sluis, Beatrijs Wolters, Jan Kluytmans, Jannie Romme, Wouter van den Bijllaardt, Linda van Mook, M.M.L (Miranda) van Rijen, Margreet Filius, Jet Gisolf, Frances Greven, Danique Huijbens, Robert Jan Hassing, Roos Pon, Lieke Preijers, Joke van Leusen, Harald Verheij, Wim Boersma, Evelien Brans, Paul Kloeg, Kitty Molenaar-Groot, Nhat Khanh Nguyen, Nienke Paternotte, Anke Rol, Lida Stooper, Helga Dijkstra, Esther Eggenhuizen, Lucas Huijs, Simone Moorlag, Mihai Netea, Eva Pranger, Esther Taks, Jaap ten Oever, Rob ter Heine, Kitty Blauwendraat, Bob Meek, Isil Erkaya, Houda Harbech, Nienke Roescher, Rifka Peeters, Menno te Riele, Carmen Zhou, Esther Calbo, Cristina Badia Marti, Emma Triviño Palomares, Tomás Perez Porcuna, Anabel Barriocanal, Ana Maria Barriocanal, Irma Casas, Jose Dominguez, Maria Esteve, Alicia Lacoma, Irene Latorre, Gemma Molina, Barbara Molina, Antoni Rosell, Sandra Vidal, Lydia Barrera, Natalia Bustos, Ines Portillo Calderón, David Gutierrez Campos, Jose Manuel Carretero, Angel Dominguez Castellano, Renato Compagnone, Encarnacion Ramirez de Arellano, Almudena de la Serna, Maria Dolores del Toro Lopez, Marie-Alix Clement Espindola, Ana Belen Martin Gutierrez, Alvaro Pascual Hernandez, Virginia Palomo Jiménez, Elisa Moreno, Nicolas Navarrete, Teresa Rodriguez Paño, Jesús Rodríguez-Baño, Enriqueta Tristán, Maria Jose Rios Villegas, Atsegiñe Canga Garces, Erika Castro Amo, Raquel Coya Guerrero, Josune Goikoetxea, Leticia Jorge, Cristina Perez, María Carmen Fariñas Álvarez, Manuel Gutierrez Cuadra, Francisco Arnaiz de las Revillas Almajano, Pilar Bohedo Garcia, Teresa Giménez Poderos, Claudia González Rico, Blanca Sanchez, Olga Valero, Noelia Vega, John Campbell, Anna Barnes, Helen Catterick, Tim Cranston, Phoebe Dawe, Emily Fletcher, Liam Fouracre, Alison Gifford, John Kirkwood, Christopher Martin, Amy McAnew, Marcus Mitchell, Georgina Newman, Abby O’Connell, Jakob Onysk, Lynne Quinn, Shelley Rhodes, Samuel Stone, Lorrie Symons, Harry Tripp, Adilia Warris, Darcy Watkins, Bethany Whale, Alex Harding, Gemma Lockhart, Kate Sidaway-Lee, Sam Hilton, Sarah Manton, Daniel Webber-Rookes, Rachel Winder, James Moore, Freya Bateman, Michael Gibbons, Bridget Knight, Julie Moss, Sarah Statton, Josephine Studham, Lydia Hall, Will Moyle, and Tamsin Venton

Subjects
Vaccine, Off-target, Immunoregulation, Cytokine, SARS-CoV-2, Heterologous immunity, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: The COVID-19 pandemic led to the rapid development and deployment of several highly effective vaccines against SARS-CoV-2. Recent studies suggest that these vaccines may also have off-target effects on the immune system. We sought to determine and compare the off-target effects of the adenovirus vector ChAdOx1-S (Oxford-AstraZeneca) and modified mRNA BNT162b2 (Pfizer-BioNTech) vaccines on immune responses to unrelated pathogens. Methods: Prospective sub-study within the BRACE trial. Blood samples were collected from 284 healthcare workers before and 28 days after ChAdOx1-S or BNT162b2 vaccination. SARS-CoV-2-specific antibodies were measured using ELISA, and whole blood cytokine responses to specific (SARS-CoV-2) and unrelated pathogen stimulation were measured by multiplex bead array. Findings: Both vaccines induced robust SARS-CoV-2 specific antibody and cytokine responses. ChAdOx1-S vaccination increased cytokine responses to heat-killed (HK) Candida albicans and HK Staphylococcus aureus and decreased cytokine responses to HK Escherichia coli and BCG. BNT162b2 vaccination decreased cytokine response to HK E. coli and had variable effects on cytokine responses to BCG and resiquimod (R848). After the second vaccine dose, BNT162b2 recipients had greater specific and off-target cytokine responses than ChAdOx1-S recipients. Interpretation: ChAdOx1-S and BNT162b2 vaccines alter cytokine responses to unrelated pathogens, indicative of potential off-target effects. The specific and off-target effects of these vaccines differ in their magnitude and breadth. The clinical relevance of these findings is uncertain and needs further study. Funding: Bill & Melinda Gates Foundation, National Health and Medical Research Council, Swiss National Science Foundation and the Melbourne Children’s. BRACE trial funding is detailed in acknowledgements.

Published
2024
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3. Bacillus Calmette-Guérin vaccination for protection against recurrent herpes labialis: a nested randomised controlled trialResearch in context

Author

Laure F. Pittet, Cecilia L. Moore, Ellie McDonald, Simone Barry, Marc Bonten, John Campbell, Julio Croda, Margareth Dalcolmo, Andrew Davidson, Mark W. Douglas, Kaya Gardiner, Amanda Gwee, Bruno Jardim, Marcus V.G. Lacerda, Michaela Lucas, David J. Lynn, Laurens Manning, Roberto D. de Oliveira, Kirsten P. Perrett, Cristina Prat-Aymerich, Peter C. Richmond, Jorge L. Rocha, Jesus Rodriguez-Baño, Adilia Warris, Nicholas J. Wood, Nicole L. Messina, Nigel Curtis, Tenaya Jamieson, Nicole Messina, Thilanka Morawakage, Susan Perlen, Kirsten Perrett, Laure Pittet, Amber Sastry, Jia Wei Teo, Francesca Orsini, Katherine Lee, Cecilia Moore, Suzanna Vidmar, Rashida Ali, Ross Dunn, Peta Edler, Grace Gell, Casey Goodall, Richard Hall, Ann Krastev, Nathan La, Nick McPhate, Thao Nguyen, Jack Ren, Luke Stevens, Ahmed Alamrousi, Rhian Bonnici, Thanh Dang, Susie Germano, Jenny Hua, Rebecca McElroy, Monica Razmovska, Scott Reddiex, Xiaofang Wang, Jeremy Anderson, Kristy Azzopardi, Vicki Bennett-Wood, Anna Czajko, Nadia Mazarakis, Conor McCafferty, Frances Oppedisano, Belinda Ortika, Casey Pell, Leena Spry, Ryan Toh, Sunitha Velagapudi, Amanda Vlahos, Ashleigh Wee-Hee, Pedro Ramos, Karina De La Cruz, Dinusha Gamage, Anushka Karunanayake, Isabella Mezzetti, Benjamin Ong, Ronita Singh, Enoshini Sooriyarachchi, Suellen Nicholson, Natalie Cain, Rianne Brizuela, Han Huang, Veronica Abruzzo, Morgan Bealing, Patricia Bimboese, Kirsty Bowes, Emma Burrell, Joyce Chan, Jac Cushnahan, Hannah Elborough, Olivia Elkington, Kieran Fahey, Monique Fernandez, Catherine Flynn, Sarah Fowler, Marie Gentile Andrit, Bojana Gladanac, Catherine Hammond, Norine Ma, Sam Macalister, Emmah Milojevic, Jesutofunmi Mojeed, Jill Nguyen, Liz O'Donnell, Nadia Olivier, Isabelle Ooi, Stephanie Reynolds, Lisa Shen, Barb Sherry, Judith Spotswood, Jamie Wedderburn, Angela Younes, Donna Legge, Jason Bell, Jo Cheah, Annie Cobbledick, Kee Lim, Sonja Elia, Lynne Addlem, Anna Bourke, Clare Brophy, Nadine Henare, Narelle Jenkins, Francesca Machingaifa, Skye Miller, Kirsten Mitchell, Sigrid Pitkin, Kate Wall, Paola Villanueva, Nigel Crawford, Wendy Norton, Niki Tan, Thilakavathi Chengodu, Diane Dawson, Victoria Gordon, Tony Korman, Jess O'Bryan, Sophie Agius, Samantha Bannister, Jess Bucholc, Alison Burns, Beatriz Camesella, John Carlin, Marianna Ciaverella, Maxwell Curtis, Stephanie Firth, Christina Guo, Matthew Hannan, Erin Hill, Sri Joshi, Katherine Lieschke, Megan Mathers, Sasha Odoi, Ashleigh Rak, Chris Richards, Leah Steve, Carolyn Stewart, Eva Sudbury, Helen Thomson, Emma Watts, Fiona Williams, Angela Young, Penny Glenn, Andrew Kaynes, Amandine Philippart De Floy, Sandy Buchanan, Thijs Sondag, Ivy Xie, Harriet Edmund, Bridie Byrne, Tom Keeble, Belle Ngien, Fran Noonan, Michelle Wearing-Smith, Alison Clarke, Pemma Davies, Oliver Eastwood, Alric Ellinghaus, Rachid Ghieh, Zahra Hilton, Emma Jennings, Athina Kakkos, Iris Liang, Katie Nicol, Sally O'Callaghan, Helen Osman, Gowri Rajaram, Sophia Ratcliffe, Victoria Rayner, Ashleigh Salmon, Angela Scheppokat, Aimee Stevens, Rebekah Street, Nicholas Toogood, Nicholas Wood, Twinkle Bahaduri, Therese Baulman, Jennifer Byrne, Candace Carter, Mary Corbett, Aiken Dao, Maria Desylva, Andrew Dunn, Evangeline Gardiner, Rosemary Joyce, Rama Kandasamy, Craig Munns, Lisa Pelayo, Ketaki Sharma, Katrina Sterling, Caitlin Uren, Clinton Colaco, Mark Douglas, Kate Hamilton, Adam Bartlett, Brendan McMullan, Pamela Palasanthiran, Phoebe Williams, Justin Beardsley, Nikki Bergant, Renier Lagunday, Kristen Overton, Jeffrey Post, Yasmeen Al-Hindawi, Sarah Barney, Anthony Byrne, Lee Mead, Marshall Plit, David Lynn, Saoirse Benson, Stephen Blake, Rochelle Botten, Tee Yee Chern, Georgina Eden, Liddy Griffith, Jane James, Miriam Lynn, Angela Markow, Domenic Sacca, Natalie Stevens, Steve Wesselingh, Catriona Doran, Alice Sawka, Sue Evans, Louise Goodchild, Christine Heath, Meredith Krieg, Helen Marshall, Mark McMillan, Mary Walker, Peter Richmond, Nelly Amenyogbe, Christina Anthony, Annabelle Arnold, Beth Arrowsmith, Rym Ben-Othman, Sharon Clark, Jemma Dunnill, Nat Eiffler, Krist Ewe, Carolyn Finucane, Lorraine Flynn, Camille Gibson, Lucy Hartnell, Elysia Hollams, Heidi Hutton, Lance Jarvis, Jane Jones, Jan Jones, Karen Jones, Jennifer Kent, Tobias Kollmann, Debbie Lalich, Wenna Lee, Rachel Lim, Sonia McAlister, Fiona McDonald, Andrea Meehan, Asma Minhaj, Lisa Montgomery, Melissa O'Donnell, Jaslyn Ong, Joanne Ong, Kimberley Parkin, Glady Perez, Catherine Power, Shadie Rezazadeh, Holly Richmond, Sally Rogers, Nikki Schultz, Margaret Shave, Patrycja Skut, Lisa Stiglmayer, Alexandra Truelove, Ushma Wadia, Rachael Wallace, Justin Waring, Michelle England, Erin Latkovic, Susan Herrmann, Marcus Lacerda, Paulo Henrique Andrade, Fabiane Bianca Barbosa, Dayanne Barros, Larissa Brasil, Ana Greyce Capella, Ramon Castro, Erlane Costa, Dilcimar de Souza, Maianne Dias, José Dias, Klenilson Ferreira, Paula Figueiredo, Thamires Freitas, Ana Carolina Furtado, Larissa Gama, Vanessa Godinho, Cintia Gouy, Daniele Hinojosa, Tyane Jardim, Joel Junior, Augustto Lima, Bernardo Maia, Adriana Marins, Kelry Mazurega, Tercilene Medeiros, Rosangela Melo, Marinete Moraes, Elizandra Nascimento, Juliana Neves, Maria Gabriela Oliveira, Thais Oliveira, Ingrid Oliveira, Arthur Otsuka, Rayssa Paes, Handerson Pereira, Gabrielle Pereira, Christiane Prado, Evelyn Queiroz, Laleyska Rodrigues, Bebeto Rodrigues, Vanderson Sampaio, Anna Gabriela Santos, Daniel Santos, Tilza Santos, Evelyn Santos, Ariandra Sartim, Ana Beatriz Silva, Juliana Silva, Emanuelle Silva, Mariana Simão, Caroline Soares, Antonny Sousa, Alexandre Trindade, Fernando Val, Adria Vasconcelos, Heline Vasconcelos, Carolinne Abreu, Katya Martinez Almeida, Camila Bitencourt de Andrade, Jhenyfer Thalyta Campos Angelo, Ghislaine Gonçalvez de Araújo Arcanjo, Bianca Maria Silva Menezes Arruda, Wellyngthon Espindola Ayala, Adelita Agripina Refosco Barbosa, Felipe Zampieri Vieira Batista, Fabiani de Morais Batista, Miriam de Jesus Costa, Mariana Garcia Croda, Lais Alves da Cruz, Roberta Carolina Pereira Diogo, Rodrigo Cezar Dutra Escobar, Iara Rodrigues Fernandes, Leticia Ramires Figueiredo, Leandro Galdino Cavalcanti Gonçalves, Sarita Lahdo, Joyce dos Santos Lencina, Guilherme Teodoro de Lima, Larissa Santos Matos, Bruna Tayara Leopoldina Meireles, Debora Quadros Moreira, Lilian Batista Silva Muranaka, Adriely de Oliveira, Karla Regina Warszawski de Oliveira, Matheus Vieira de Oliveira, Roberto Dias de Oliveira, Andrea Antonia Souza de Almeida dos Reis Pereira, Marco Puga, Caroliny Veron Ramos, Thaynara Haynara Souza da Rosa, Karla Lopes dos Santos, Claudinalva Ribeiro dos Santos, Dyenyffer Stéffany Leopoldina dos Santos, Karina Marques Santos, Paulo César Pereira da Silva, Paulo Victor Rocha da Silva, Débora dos Santos Silva, Patricia Vieira da Silva, Bruno Freitas da Rosa Soares, Mariana Gazzoni Sperotto, Mariana Mayumi Tadokoro, Daniel Tsuha, Hugo Miguel Ramos Vieira, Margareth Maria Pretti Dalcolmo, Cíntia Maria Lopes Alves da Paixão, Gabriela Corrêa E Castro, Simone Silva Collopy, Renato da Costa Silva, Samyra Almeida da Silveira, Alda Maria Da-Cruz, Alessandra Maria da Silva Passos de Carvalho, Rita de Cássia Batista, Maria Luciana Silva De Freitas, Aline Gerhardt de Oliveira Ferreira, Ana Paula Conceição de Souza, Paola Cerbino Doblas, Ayla Alcoforado da Silva dos Santos, Vanessa Cristine de Moraes dos Santos, Dayane Alves dos Santos Gomes, Anderson Lage Fortunato, Adriano Gomes-Silva, Monique Pinto Gonçalves, Paulo Leandro Garcia Meireless Junior, Estela Martins da Costa Carvalho, Fernando do Couto Motta, Ligia Maria Olivo de Mendonça, Girlene dos Santos Pandine, Rosa Maria Plácido Pereira, Ivan Ramos Maia, Jorge Luiz da Rocha, João Victor Paiva Romano, Glauce dos Santos, Erica Fernandes da Silva, Marilda Agudo Mendonça Teixeira de Siqueira, Ágatha Cristinne Prudêncio Soares, Sandra Franch Arroyo, Henny Ophorst-den Besten, Anna Boon, Karin M. Brakke, Axel Janssen, Marijke A.H. Koopmans, Toos Lemmens, Titia Leurink, Engelien Septer-Bijleveld, Kimberly Stadhouders, Darren Troeman, Marije van der Waal, Marjoleine van Opdorp, Nicolette van Sluis, Beatrijs Wolters, Jan Kluytmans, Jannie Romme, Wouter van den Bijllaardt, Linda van Mook, M.M.L (Miranda) van Rijen, P.M.G. Filius, Jet Gisolf, Frances Greven, Danique Huijbens, Robert Jan Hassing, R.C. Pon, Lieke Preijers, J.H. van Leusen, Harald Verheij, Wim Boersma, Evelien Brans, Paul Kloeg, Kitty Molenaar-Groot, Nhat Khanh Nguyen, Nienke Paternotte, Anke Rol, Lida Stooper, Helga Dijkstra, Esther Eggenhuizen, Lucas Huijs, Simone Moorlag, Mihai Netea, Eva Pranger, Esther Taks, Jaap ten Oever, Rob ter Heine, Kitty Blauwendraat, Bob Meek, Isil Erkaya, Houda Harbech, Nienke Roescher, Rifka Peeters, Menno te Riele, Carmen Zhou, Esther Calbo, Cristina Badia Marti, Emma Triviño Palomares, Tomás Perez Porcuna, Anabel Barriocanal, Ana Maria Barriocanal, Irma Casas, Jose Dominguez, Maria Esteve, Alicia Lacoma, Irene Latorre, Gemma Molina, Barbara Molina, Antoni Rosell, Sandra Vidal, Lydia Barrera, Natalia Bustos, Ines Portillo Calderón, David Gutierrez Campos, Jose Manuel Carretero, Angel Dominguez Castellano, Renato Compagnone, Encarnacion Ramirez de Arellano, Almudena de la Serna, Maria Dolores del Toro Lopez, Marie-Alix Clement Espindola, Ana Belen Martin Gutierrez, Alvaro Pascual Hernandez, Virginia Palomo Jiménez, Elisa Moreno, Nicolas Navarrete, Teresa Rodriguez Paño, Jesús Rodríguez-Baño, Enriqueta Tristán, Maria Jose Rios Villegas, Atsegiñe Canga Garces, Erika Castro Amo, Raquel Coya Guerrero, Josune Goikoetxea, Leticia Jorge, Cristina Perez, María Carmen Fariñas Álvarez, Manuel Gutierrez Cuadra, Francisco Arnaiz de las Revillas Almajano, Pilar Bohedo Garcia, Teresa Giménez Poderos, Claudia González Rico, Blanca Sanchez, Olga Valero, Noelia Vega, Anna Barnes, Helen Catterick, Tim Cranston, Phoebe Dawe, Emily Fletcher, Liam Fouracre, Alison Gifford, John Kirkwood, Christopher Martin, Amy McAnew, Marcus Mitchell, Georgina Newman, Abby O'Connell, Jakob Onysk, Lynne Quinn, Shelley Rhodes, Samuel Stone, Lorrie Symons, Harry Tripp, Darcy Watkins, Bethany Whale, Alex Harding, Gemma Lockhart, Kate Sidaway-Lee, Sam Hilton, Sarah Manton, Daniel Webber-Rookes, Rachel Winder, James Moore, Freya Bateman, Michael Gibbons, Bridget Knight, Julie Moss, Sarah Statton, Josephine Studham, Lydia Hall, Will Moyle, and Tamsin Venton

Subjects
Herpes simplex virus, Cold sore, Herpes labialis, Bacille Calmette-Guérin, Mycobacterium bovis, Prevention, Medicine (General), R5-920
Abstract

Summary: Background: Recurrences of herpes simplex virus (HSV) in the orofacial region (herpes labialis or cold sores) impact quality-of-life. We aimed to study whether the bacille Calmette-Guérin (BCG) vaccine can attenuate cold sore recurrences through off-target immunomodulatory effects. Methods: In this nested randomised controlled trial within the multicentre, phase 3 BRACE trial, 6828 healthcare workers were randomised in 36 sites in Australia, the Netherlands, Spain, the United Kingdom and Brazil, to receive BCG-Denmark or no BCG (1:1 ratio using a web-based procedure) and followed for 12 months with 3-monthly questionnaires. Exclusion criteria included contraindication to BCG vaccine or previous vaccination with BCG within the past year, any other live-attenuated vaccine within the last month, or any COVID-specific vaccine. The intervention group received one intradermal dose of 0.1 mL of BCG-Denmark corresponding to 2−8 x 105 colony forming units of Mycobacterium bovis, Danish strain 1331. The primary outcome was the difference in restricted mean survival time (i.e., time to first cold-sore recurrence), in participants with frequent recurrent herpes labialis (≥4 recurrences/year), analysed by intention-to-treat. Secondary outcomes addressed additional questions, including analyses in other sub-populations. Adverse events were monitored closely during the first 3 months and were reported in all participants who received one dose of study drug according to intervention received. The BRACE trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020 and February 18, 2021, 84 individuals with frequent recurrent cold sores were randomly assigned to BCG (n = 38) or control (n = 46). The average time to first cold-sore recurrence was 1.55 months longer in the BCG group (95% CI 0.27–2.82, p = 0.02) than the control group (hazard ratio 0.54, 95% CI 0.32–0.91; intention-to-treat). The beneficial effect of BCG was greater in the as-treated population (difference 1.91 months, 95% CI 0.69–3.12, p = 0.003; hazard ratio 0.45, 95% CI 0.26–0.76). In prespecified subgroup analyses, only sex modified the treatment effect (interaction p = 0.007), with benefit restricted to males. Over 12 months, a greater proportion of participants in the BCG group compared with the control group reported a decrease in duration (61% vs 21%), severity (74% vs 21%), frequency (55% vs 21%), and impact on quality of life (42% vs 15%) of cold sore recurrences. In participants who had ever had a cold sore, there was also a decrease in self-reported burden of recurrences in the BCG group. In participants who had never had a cold sore, there was an increased risk of a first episode in the BCG group (risk difference 1.4%; 95% CI 0.3–2.6%, p = 0.02). There were no safety concerns. Interpretation: BCG-Denmark vaccination had a beneficial effect on herpes labialis, particularly in males with frequent recurrences, but may increase the risk of a first cold sore. Funding: Bill & Melinda Gates Foundation, the Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, and individual donors.

Published
2023
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4. Serial changes in liquid biopsy-derived variant allele frequency predict immune checkpoint inhibitor responsiveness in the pan-cancer setting

Author

Shumei Kato, Bing Li, Jacob J. Adashek, Seong Won Cha, Daniella Bianchi-Frias, Dajun Qian, Lisa Kim, Tiffany W so, Marcus Mitchell, Naoki Kamei, Robert Hoiness, Jayne Hoo, Phillip N. Gray, Teruaki Iyama, Masahide Kashiwagi, Hsiao-Mei Lu, and Razelle Kurzrock

Subjects
Immune checkpoint inhibitor, liquid biopsy, response, cancer, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Major immunotherapy challenges include a limited number of predictive biomarkers and the unusual imaging features post-therapy, such as pseudo-progression, which denote immune infiltrate-mediated tumor enlargement. Such phenomena confound clinical decision-making, since the cancer may eventually regress, and the patient should stay on treatment. We prospectively evaluated serial, blood-derived cell-free DNA (cfDNA) (baseline and 2–3 weeks post-immune checkpoint inhibitors [ICIs]) for variant allele frequency (VAF) and blood tumor mutation burden (bTMB) changes (next-generation sequencing) (N = 84 evaluable patients, diverse cancers). Low vs. high cfDNA-derived average adjusted ΔVAF (calculated by a machine-learning model) was an independent predictor of higher clinical benefit rate (stable disease ≥6 months/complete/partial response) (69.2% vs. 22.5%), and longer median progression-free (10.1 vs. 2.25 months) and overall survival (not reached vs. 6.1 months) (all P

Published
2022
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5. BCG vaccination to reduce the impact of COVID-19 in healthcare workers: Protocol for a randomised controlled trial (BRACE trial)

Author

Donna Legge, Katherine J Lee, Rachel Dixon, Amanda Gwee, Nigel Curtis, Helen Marshall, Fiona McDonald, Nick Evans, Adam Finn, Mark McMillan, Peter Richmond, Joyce Chan, John Carlin, Anthony Byrne, Helen Thomson, Richard Hall, Jesús Rodríguez-Baño, Robert Harrison, Kirsten P Perrett, Michaela Lucas, Sue Evans, Melissa O’Donnell, Justin Waring, Andrew Davidson, Heidi Hutton, Laure F Pittet, Jan Kluytmans, Ana Maria Barriocanal, Emily Fletcher, James Moore, John Campbell, Kate Sidaway-Lee, Alex Harding, Katherine Lee, David Paterson, Juliana Silva, Michael Gibbons, Denise Faustman, Nicole L Messina, Kaya Gardiner, Frank Shann, Veronica Abruzzo, Susie Germano, Laurens Manning, Justin Beardsley, Jason Bell, Francesca Orsini, Jeremy Anderson, Kim Mulholland, Andrew Dunn, Jeffrey Post, Catherine Flynn, Clare Seamark, Andrew Steer, Sigrid Pitkin, Emma Watts, Carlos Garcia, Kristen Overton, Daniel Santos, Christina Guo, Antoni Rosell, Sarah Fowler, Richard Malley, Nicholas J Wood, Wim Boersma, Kanta Subbarao, Karen Jones, Chris Richards, Nigel Crawford, Adilia Warris, Mary Corbett, Pamela Palasanthiran, Cristina Pérez, Esther Calbo, Shelley Rhodes, Brendan McMullan, Jane Jones, Wendy Norton, Luke Stevens, Craig F Munns, Louise Goodchild, Mary Walker, Bridget Knight, Thilanka Morawakage, Josune Goikoetxea, Teresa Rodrigues, Nienke Roescher, David Seamark, Jorge Rocha, Stephanie Reynolds, Lynne Quinn, Harry Tripp, Tobias R Kollmann, Marc Bonten, Steve Wesselingh, Irene Latorre, Maria Esteve, Kate Hamilton, Angela Young, Cristina Prat-Aymerich, NICK WOOD, RAMÓN CASTRO, Ruth Warren, Christopher Martin, Diane Dawson, Lorrie Symons, Ann Krastev, Ellie McDonald, Claudia González Rico, Ester Valls, Julio Croda, Tobias Kollmann, Victoria Gordon, Marcus Vinícius Guimarães Lacerda, Jennifer Kent, Samantha Bannister, Margareth Dalcolmo, Sonja Elia, Casey Goodall, Tenaya Jamieson, Bruno Jardim, David J Lynn, Cristina Prat Aymerich, Eva Sudbury, Paola Villanueva, Katherine Lieschke, Carolinne Abreu, Lynne Addlem, Sophie Agius, Adelita Agripina Barbosa, Ahmed Alamrousi, Ayla Alcoforado Santos, Yasmeen Al-Hindawi, Samyra Almeida Da Silveira, Lais Alves Cruz, Christina Anthony, Andrea Antonia Pereira, Francisco Arnaiz Almajano, Annabelle Arnold, Beth Arrowsmith, Kristy Azzopardi, Cristina Badia Marti, Twinkle Bahaduri, Sarah Barney, Lydia Barrera, Anabel Barriocanal, Dayanne Barros, Adam Bartlett, Lilian Muranaka, Therese Baulman, Morgan Bealing, Ana Belen Gutierrez, Vicki Bennett-Wood, Nikki Bergant, Fabiane Bianca Barbosa, Wouter Bijllaardt, Patricia Bimboese, Camila Bitencourt Andrade, Kitty Blauwendraat, Pilar Bohedo Garcia, Rhian Bonnici, Anne Boon, Anna Bourke, Kirsty Bowes, Larissa Brasil, Clare Brophy, Sandy Buchanan, Jess Bucholc, Alison Burns, Emma Burrell, Natalia Bustos, Bridie Byrne, Jorge Calvo Montes, Beatriz Camesella, Atsegiñe Cangas, Maria Carmen Roque, Roberta Carolina Diogo, Estela Carvalho, Irma Casas, Erika Castro, Helen Catterick, Rodrigo Cezar Escobar, Jo Cheah, Thilakavathi Chengodu, Marianna Ciaverella, Sharon Clark, Marie-Alix Clement Espindola, Annie Cobbledick, Clinton Colaco, Simone Collopy, Patricia Comella, Gabriela Correa Castro, Erlane Costa, Raquel Coya, Alda Cruz, Jac Cushnahan, Anna Czajko, Renato da Silva, Bouchra Daitiri, Karen Dalton, Aiken Dao, Phoebe Dawe, Miriam Jesus Costa, Karina De La Cruz, Almudena de Serna, Fabiani de Morais Batista, Adriely de Oliveira, Rocio del Rey Morillo, Maria Desylva, Helga Dijkstra, Maria Dolores Lopez, Jose Dominguez, Angel Dominguez Castellano, Glauce Dos Santos, Joyce Santos Lencina, Débora Santos Silva, Mark Douglas, Ross Dunn, Jemma Dunnill, Harriet Edmund, Nat Eiffler, Hannah Elborough, Olivia Elkington, Michelle England, Wellyngthon Espindola Ayala, Krist Ewe, María Carmen Álvarez, Kieran Fahey, Jill Fairweather, Erica Fernandes Silva, Monique Fernandez, Galina Fidler, P.M.G. Filius, Carolyn Finucane, Stephanie Firth, Lorraine Flynn, Liam Fouracre, Thamires Freitas, Ana Carolina Furtado, Maria Gabriela Oliveira, Anna Gabriela Santos, Leandro Galdino Gonçalves, Laura Galletta, Larissa Gama, Dinusha Gamage, Radhika Ganpat, Mariana Garcia Croda, Evangeline Gardiner, Grace Gell, Aline Gerhardt Oliveira, Camille Gibson, Alison Gifford, Teresa Giménez Poderos, Ann Ginsberg, Jet Gisolf, Bojana Gladanac, Penny Glenn, Vanessa Godinho, Mayara Góes Santos, Telma Goldenberg, Adriano Gomes, Susana Gonzalez Marcos, Frances Greven, Ana Greyce Capella, David Gutierrez Campos, Manuel Gutierrez Cuadra, Lydia Hall, Matthew Hannan, Houda Harbech, Neil Haker, Robert Jan Hassing, Thaynara Haynara Rosa, Zaheerah Haywood, Nadine Henare, Paulo Henrique Andrade, Susan Herrmann, Erin Hill, Sam Hilton, Danique Huijbens, Axel Janssen, Tyane Jardim, Lance Jarvis, Narelle Jenkins, Jan Jones, Leticia Jorge, Maria Jose Vilegas, Sri Joshi, Rosemary Joyce, Joel Junior, Rama Kandasamy, Anushka Karunanayake, Hana Karuppasamy, Tom Keeble, Paul Kloeg, Tony Korman, Nathan La, Marcus Lacerda, Alicia Lacoma, Renier Lagunday, Debbie Lalich, Erin Latkovic, Paulo Leandro Junior, Toos Lemmers, Titia Leurink, Kee Lim, Gemma Lockhart, Cíntia Lopes Bogéa, Karla Lopes Santos, Reyes Lopez Marques, Maria Luciana Freitas, Norine Ma, Sam Macalister, Cristiane Machado, Matheus Machado Ramos, Francesca Machingaifa, Ivan Maia, Bernardo Maia, Sarah Manton, Jose Manuel Carrerero, Cíntia Maria Alves, Rosa Maria Pereira, Bianca Maria Arruda, Adriana Marins, Katya Martinez Almeida, Wayne Mather, Megan Mathers, Fábio Mauricio Gomes, Mariana Mayumi Tadokoro, Nadia Mazarakis, Kelry Mazurega, Sonia McAlister, Amy McAndrews, Rebecca McElroy, Nick McPhate, Lee Mead, Andrea Meehan, Bob Meek, Rosangela Melo, Guillermo Mena, Daniella Mesquita, Nicole Messina, Isabella Mezzetti, Hugo Miguel Vieira, Skye Miller, Kirsten Mitchell, Marcus Mitchell, Jesutofunmi Mojeed, Kitty Molenaar, Gemma Molina, Barbara Molina, Lisa Montgomery, Cecilia Moore, Simone Moorlag, Julie Moss, Will Moyle, Craig Munns, Elizandra Nascimento, Nicolas Navarrette, Mihai Netea, Juliana Neves, Georgina Newman, Belle Ngien, Jill Nguyen, Khanh Nguyen, Fran Noonan, Jess O’Bryan, Abby O’Connell, Sasha Odoi, Liz O’Donnell, Roberto Oliveira, Marilena Oliveira, Thais Oliveira, Ingrid Oliveira, Nadia Olivier, Ligia Olivio, Benjamin Ong, Jaslyn Ong, Joanne Ong, Jakob Onysk, Isabelle Ooi, Frances Oppedisano, Belinda Ortika, Orygen Group, Arthur Otsuka, Rosie Owens, Rayssa Paes, Virginia Palomo Jiménez, Girlene Pandine, Kimberley Parkin, Alvaro Pascual Hernandez, Nienke Paternotte, Ana Paula Souza, Lisa Pelayo, Casey Pell, Sille Pelser, Handerson Pereira, Gabrielle Pereira, Glady Perez, Tomás Perez Porcuna, Susan Perlen, Kirsten Perrett, Amandine Philippart Floy, Laure Pittet, R.C. Pon, Ines Portillo Calderón, Catherine Power, Christiane Prado, Endriaen Prajitno, Lieke Preijers, Marco Puga, Evelyn Queiroz, Ashleigh Rak, Leticia Ramires Figueiredo, Encarnacion Ramirez de Arellano, Pedro Ramos, Karla Regina Oliveira, Jack Ren, Claudinalva Ribeiro Santos, Holly Richmond, Ana Rita Souza, Laleyska Rodrigues, Bebeto Rodrigues, Iara Rodrigues Fernandes, Sally Rogers, Anke Rol, Jannie Romme, Maria Roser Font, Sonia Sallent, Vanderson Sampaio, Nuria Sanchez, Blanca Sanchez, Tilza Santos, Ariandra Sartim, Amber Sastry, Alice Sawka, Nikki Schultz, Engelien Septer-Bijleveld, Raquel Serrano, Ketaki Sharma, Margaret Shave, Lisa Shen, Adrian Siles Baena, Rafaela Silva, Emanuelle Silva, Mariana Simão, Ronita Singh, Marilda Siqueira, Marciléia Soares Chaves, Thijs Sondag, Enoshini Sooriyarachchi, Antonny Sousa, Leena Spry, Sarah Statton, Dyenyffer Stéffany Santos, Katrina Sterling, Leah Steve, Carolyn Stewart, Lisa Stiglmayer, Lida Stooper, Josephine Studham, Astrid Suiker, Esther Taks, Niki Tan, Bruna Tayara Meireles, Menno te Riele, Jaap ten Oever, Guilherme Teodoro Lima, Jhenyfer Thalyta Angelo, Ryan Toh, Alexandre Trindade, Enriqueta Tristán, Darren Troeman, Alexandra Truelove, Daniel Tsuha, Marlot Uffing, Fernando Val, Olga Valero, Chantal van Ven, Leo Van Heuvel, Sigrid van Veen, Marije van Waal, J.H. van Leusen, Linda van Mook, H. van Onzenoort, Marjoleine van Opdorp, Miranda van Rijen, Nicolette van Sluis, Adria Vasconcelos, Noelia Vega, Sunitha Velagapudi, Louise Vennells, Tamsin Venton, Harald Verheij, P.M. Verhoeven, Caroliny Veron Ramos, Paulo Victor Silva, Sandra Vidal, Patricia Vieira, Matheus Vieira Oliveira, Rosario Vigo Ortega, Raquel Villar, Amanda Vlahos, Ushma Wadia, Kate Wall, Rachael Wallace, Michelle Wearing-Smith, Daniel Webber-Rookes, Jamie Wedderburn, Ashleigh Wee-Hee, Jia Wei Teo, Bethany Whale, Phoebe Williams, Beatrijs Wolters, Ivy Xie, Angela Younes, Felipe Zampieri Batista, Carmen Zhou, Vivian Zwart, Simone Barry, Saoirse Benson, Stephen Blake, Rochelle Botten, Tee Yee Chern, Catriona Doran, Georgina Eden, Liddy Griffith, Christine Heath, Jane James, Meredith Krieg, David Lynn, Miriam Lynn, Angela Markow, Domenic Sacca, Natalie Stevens, and Rob ter Heine

Subjects
Medicine
Abstract

Introduction BCG vaccination modulates immune responses to unrelated pathogens. This off-target effect could reduce the impact of emerging pathogens. As a readily available, inexpensive intervention that has a well-established safety profile, BCG is a good candidate for protecting healthcare workers (HCWs) and other vulnerable groups against COVID-19.Methods and analysis This international multicentre phase III randomised controlled trial aims to determine if BCG vaccination reduces the incidence of symptomatic and severe COVID-19 at 6 months (co-primary outcomes) compared with no BCG vaccination. We plan to randomise 10 078 HCWs from Australia, The Netherlands, Spain, the UK and Brazil in a 1:1 ratio to BCG vaccination or no BCG (control group). The participants will be followed for 1 year with questionnaires and collection of blood samples. For any episode of illness, clinical details will be collected daily, and the participant will be tested for SARS-CoV-2 infection. The secondary objectives are to determine if BCG vaccination reduces the rate, incidence, and severity of any febrile or respiratory illness (including SARS-CoV-2), as well as work absenteeism. The safety of BCG vaccination in HCWs will also be evaluated. Immunological analyses will assess changes in the immune system following vaccination, and identify factors associated with susceptibility to or protection against SARS-CoV-2 and other infections.Ethics and dissemination Ethical and governance approval will be obtained from participating sites. Results will be published in peer-reviewed open-access journals. The final cleaned and locked database will be deposited in a data sharing repository archiving system.Trial registration ClinicalTrials.gov NCT04327206

Published
2021
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6. The effect of health insurance coverage and the doctor-patient relationship on health care utilization in high poverty neighborhoods

Author

Destini A. Smith, Alan Akira, Kenneth Hudson, Andrea Hudson, Marcellus Hudson, Marcus Mitchell, and Errol Crook

Subjects
Health insurance, Usual provider, Hypertension, Screening, Preventative care, Minority health, Health disparities, Medicine
Abstract

African Americans have higher rates of mortality than whites who are the same age and sex. We hypothesize that in low socioeconomic status neighborhoods, having health insurance coverage and a regular health care provider increases the likelihood of receiving diagnostic tests for cardiovascular disease and diabetes. We use data from a random two-stage cluster sample of 230 adults living in high poverty census tracts to examine the effects of insurance coverage and having a regular doctor on the likelihood receiving diagnostic tests for high cholesterol, high blood sugar, and blood pressure. We find that health insurance coverage increases the odds of having a regular health care provider (p

Published
2017
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8. Text Chunking using Transformation-Based Learning

Author

Ramshaw, Lance A. and Marcus, Mitchell P.

Subjects
Computer Science - Computation and Language
Abstract

Eric Brill introduced transformation-based learning and showed that it can do part-of-speech tagging with fairly high accuracy. The same method can be applied at a higher level of textual interpretation for locating chunks in the tagged text, including non-recursive ``baseNP'' chunks. For this purpose, it is convenient to view chunking as a tagging problem by encoding the chunk structure in new tags attached to each word. In automatic tests using Treebank-derived data, this technique achieved recall and precision rates of roughly 92% for baseNP chunks and 88% for somewhat more complex chunks that partition the sentence. Some interesting adaptations to the transformation-based learning approach are also suggested by this application., Comment: 13 pages, LaTeX2e, 1 included figure

Published
1995

9. Exploring the Statistical Derivation of Transformational Rule Sequences for Part-of-Speech Tagging

Author

Ramshaw, Lance A. and Marcus, Mitchell P.

Subjects
Computer Science - Computation and Language
Abstract

Eric Brill has recently proposed a simple and powerful corpus-based language modeling approach that can be applied to various tasks including part-of-speech tagging and building phrase structure trees. The method learns a series of symbolic transformational rules, which can then be applied in sequence to a test corpus to produce predictions. The learning process only requires counting matches for a given set of rule templates, allowing the method to survey a very large space of possible contextual factors. This paper analyses Brill's approach as an interesting variation on existing decision tree methods, based on experiments involving part-of-speech tagging for both English and ancient Greek corpora. In particular, the analysis throws light on why the new mechanism seems surprisingly resistant to overtraining. A fast, incremental implementation and a mechanism for recording the dependencies that underlie the resulting rule sequence are also described., Comment: 10 pages, in proceedings of the ACL Balancing Act workshop

Published
1994

10. Pearl: A Probabilistic Chart Parser

Author

Magerman, David M. and Marcus, Mitchell P.

Subjects
Computer Science - Computation and Language
Abstract

This paper describes a natural language parsing algorithm for unrestricted text which uses a probability-based scoring function to select the "best" parse of a sentence. The parser, Pearl, is a time-asynchronous bottom-up chart parser with Earley-type top-down prediction which pursues the highest-scoring theory in the chart, where the score of a theory represents the extent to which the context of the sentence predicts that interpretation. This parser differs from previous attempts at stochastic parsers in that it uses a richer form of conditional probabilities based on context to predict likelihood. Pearl also provides a framework for incorporating the results of previous work in part-of-speech assignment, unknown word models, and other probabilistic models of linguistic features into one parsing tool, interleaving these techniques instead of using the traditional pipeline architecture. In preliminary tests, Pearl has been successful at resolving part-of-speech and word (in speech processing) ambiguity, determining categories for unknown words, and selecting correct parses first using a very loosely fitting covering grammar., Comment: 7 pages

Published
1994

12. Neutralising antibody potency against SARS-CoV-2 wild-type and omicron BA.1 and BA.4/5 variants in patients with inflammatory bowel disease treated with infliximab and vedolizumab after three doses of COVID-19 vaccine (CLARITY IBD): an analysis of a prospective multicentre cohort study

Author

Zhigang Liu, Kaixing Le, Xin Zhou, James L Alexander, Simeng Lin, Claire Bewshea, Neil Chanchlani, Rachel Nice, Timothy J McDonald, Christopher A Lamb, Shaji Sebastian, Klaartje Kok, Charlie W Lees, Ailsa L Hart, Richard C Pollok, Rosemary J Boyton, Daniel M Altmann, Katrina M Pollock, James R Goodhand, Nicholas A Kennedy, Tariq Ahmad, Nick Powell, Madiha Islam, Nick Croft, Bessie Cipriano, Caroline Francia, Nosheen Khalid, Ashley Kingston, Irish Lee, Anouk Lehmann, Kinnari Naik, Kevin Samuels, Nicolene Plaatjies, Hafiza Khatun, Farjana Bokth, Elise Pabriaga, Rebecca Saich, Hayley Cousins, Wendy Fraser, Rachel Thomas, Matthew Brown, Benjamin White, Nikolaos Kirkineziadis, Bernadette Tilley, Pennie Porter, Rachel Bryant, Natalia Robaczewska, Rafeeq Muhammed, Rehana Bi, Catherine Cotter, Jayne Grove, Kate Hong, Ruth Howman, Monica Mitchell, Sophie Clayton, Louise Rogers, Sugrah Sultan, Melanie Rooney, Charlotte Cottrill, Salil Singh, Chris Dawe, Robert Hull, Natalie Silva, Julie Chadwick, Laura Robertson, Jonathan Manning, Lauren Finlayson, Allison Roebuck, Joy Dawson, Sunil Sonwalkar, Naomi Chambers, Matthew Robinson, Andrew Haigh, Lear Matapure, Tim Raine, Varun George, Christina Kapizioni, Konstantina Strongili, Tina Thompson, Mohamed Ahmed, Christos Kontos, Claire Dawson, Christophe Bourges, Isabella Barbutti, Megan E Gozzard, Philip Hendy, Rhian Bull, Patricia Costa, Lisa Davey, Hayley Hannington, Kribashnie Nundlall, Catarina Martins, Laura Avanzi, Jaime Carungcong, Sabrina Barr, Richard Appleby, Emma Johnson, Eathar Shakweh, Kath Phillis, Rachel Gascoyne, Amanda Crowder, Amanda Whileman, Ian London, Jenny Grounds, Emmeline Martin, Susie Pajak, Jude Price, Kathryn Cawley, Sandra Powell, Nichola Kearsley, Anjan Dhar, Ellen Brown, Amanda Cowton, Kimberley Stamp, Ben Warner, Carmel Stuart, Louise Lacey, Shanika de Silva, Clare Allcock, Philip Harvey, Lesley Jones, Elise Cooke, Jayne Slater, Dominic King, Johanne Brooks, Pearl Baker, Hannah Beadle, Carina Cruz, Debbie Potter, Joe Collum, Farzana Masters, Aashish Kumar, Samantha Coetzee, Mihaela Peiu, Becky Icke, Jill Williams, Meena Raj, Edward Gaynor, Sibongile Chadokufa, Bonita Huggett, Hamza Meghari, Sara El-Khouly, Fevronia Kiparissi, Waffa Girshab, Lynda Russell-Walker, Christopher Jackson, Sara Sidler, Andrew Claridge, Emily Fowler, Laura McCafferty, Lesley Haxton, Peter Irving, Karolina Christodoulides, Angela Clifford, Patrick Dawson, Sailish Honap, Samuel Lim, Raphael Luber, Karina Mahiouz, Susanna Meade, Parizade Raymode, Rebecca Reynolds, Anna Stanton, Sherill Tripoli, Naomi Hare, Sopuluchukwu Odukwe, Senthuran Balachandran, Emma North, Jessica North, Bria Browne, Jessica Cordle, Ella Jameson, Yih Harn Siaw, Lane Manzano, Jonathan Segal, Ibrahim Al-Bakir, Imran Khakoo, Sofiya Portukhay, Nora Thoua, Katherine Davidson, Jagrul Miah, Lisa Canclini, Alex Hall, Hassina Furreed, Christine Mitchell-Inwang, Melony Hayes, Sally Myers, Alison Talbot, Jack Turnbull, Emma Whitehead, Katie Stamp, Alison Pattinson, Verghese Mathew, Leanne Sherris, Julie Wilcox, Sankaranarayanan Ramachandran, Hayley Robertson, Angela Harvey, Lucy Hicks, Tara-Marie Byrne, Leilani Cabreros, Hannah Downing-Wood, Sophie Hunter, Mohammad Aamir Saifuddin, Hemanth Prabhudev, Sharmili Balarajah, Jan Krucznski, Kalliopi Driva, Andrea D'Mello, Parith Shah, Rocio Castro-Seoane, Hajir Ibraheim, Laura E Constable, Jonathan W Lo, Melissa Torkizadeh, Sherine K Hermangild, Helen Sutherland, Elva Wilhelmsen, Katherine Mackintosh, Ajay M Verma, Juliemol Sebastian, Mohammad Farhad Peerally, Anne-marie Guerdette, Susan Coburn, Ching Yee Novem lam, Donna Durrant, Belinda Schaefer, Solange Serna, Muhammad Shahzad, Alexandra Kent, Lee Meng Choong, Benedetta Pantaloni, Pantelis Ravdas, Babu Vadamalayan, Stephen Foley, Becky Arnold, Cheryl Heeley, Wayne Lovegrove, Donna Sowton, Lynne Allsop, Heidi Gregory, Mandy Gill, Megan Holmes, Valeria Balan, Susan Smith, Sarah Turner, Philip J Smith, Alan Steel, Giovanna Bretland, Sarah King, Martina Lofthouse, Lindsey Rigby, Sreedhar Subramanian, David Tyrer, Kate Martin, Christopher Probert, Nikolaos Kamperidis, Temi Adedoyin, Manisha Baden, Jeannette Brown, Feba Chacko, Lisa Young, Michela Cicchetti, Mohammad Saifuddin, Priya Yesupatham, Rohit Gowda, Maureen Williams, Karen Kemp, Rima Akhand, Glaxy Gray, Anu John, Maya John, Tasnim Mohammed, Diamond Sathe, Natasha Jones, Jennifer Soren, Michael Sprakes, Julie Burton, Patricia Kane, Stephanie Lupton, Jacqueline Bartholomew, Elizabeth Denis, Alison Daniels, George MacFaul, Diane Scaletta, Loria Siamia, Felicity Williams, Chloe Green, Zeljka Ver, Chris Lamb, Mary Doona, Ashleigh Hogg, Lesley Jeffrey, Andrew King, R Alexander Speight, Jennifer Doyle, Ruth Owen, Jenny Haworth, Linda Patterson, Vithusa Varnaulasingam, Craig Mowat, Debbie Rice, Susan MacFarlane, Anne MacLeod, Samera Mohammed, Shona Murray, Anne Elliott, Mary Anne Morris, Louise Coke, Grace Hindle, Eirini Kolokouri, Catherine Wright, Claire Lee, Nicola Ward, Adele Dann, Melanie Lockett, Charlotte Cranfield, Louise Jennings, Ankur Srivastava, Lana Ward, Nouf Jeynes, Poonam Ranga, Praveen Rajasekhar, Lisa Gallagher, Jill Ward, Rae Basnett, Judy Murphy, Lauren Parking, Emma Lawson, Stacey Short, David Devadason, Gordon Moran, Neelam Khan, Lauren Tarr, Charmaine Olivia, Samantha Warbarton, Sian Kelly, Jimmy Limdi, Kay Goulden, Asad Javed, Lauren McKenzie, Julie Melville, Eleanor Liu, Joseph Sabine, Patricia Jacob, Denise McSorland, Nick Schofield, Lisa Cornwall, James Quirke, Emma Crook, Anne Turner, Pradeep Bhandari, Michelle Baker-Moffatt, Joanne Dash, Alison Le Poidevin, Hayley Downe, Lucille Bombeo, Helen Blackman, Rebecca Smith, Alan Wiles, Hannah Bloxham, Jose Dias, Evelyn Nadar, Hollie Curgenven, Ellie Gilham, Jonathan Macdonald, Shona Finan, Faye McMeeken, Misbah Mahmood, Stephanie Shields, John Paul Seenan, Des DeSilva, Susanna Malkakorpi, Rachel Carson, Holly Lawrence, Ofori Boateng, Felix Kpodo, Simon Whiteoak, Kelli Edger-Earley, Luke Vamplew, Joanna Samways, Sue Roffe, Sarah Ingram, Joel James, Sharon Botfield, Fiona Hammonds, Clare James, Zoe Berry, Gemma Aspinall, Sarah Hawkins, Marian Parkinson, Helen Gardner-Thorpe, Suzie Marriott, Clare Redstone, Halina Windak, Ana-Marie Adam, Hannah Mabb, Emma Stevenson, Jessica Record, Charles Murray, Cynthia Diaba, Fexy Joseph, Glykeria Pakou, Yvonne Gleeson, Annalyn Nunag, James Berrill, Natalie Stroud, Carla Pothecary, Lisa Roche, Keri Turner, Lisa Deering, Lynda Israel, Evelyn Baker, Maxine Nash, Andrew Fagbemi, Felicia Jennings, Imelda Mayor, Jill Wilson, Alice Wheeler, Nicola Phillips, John Gordon, Emma Levell, Silvia Zagalo, Ina Hoad, Bindu Anil, Richard Russell, Paul Henderson, Margaret Millar, Christopher Alexakis, Natalia Michalak, Cheryl Marriott, Sarah Stone, Veronika Pristopan, John Saunders, Helen Burton, Vanessa Cambridge, Tonia Clark, Charlotte Ekblad, Sarah Hierons, Joyce Katebe, Emma Saunsbury, Rachel Perry, Matthew Brookes, Kathryn Davies, Marie Green, Ann Plumbe, Clare Ormerod, Helen Christensen, Hannah Howlett, Anne Keen, Jonathan Ogor, Marie Greenhaigh, Karen Knowles, Shanzi Yin, Maria Poulaka, Alpha Anthony, Emily Newitt, Fiona Trim, Ruth Casey, Katherine Seymour, Catherine Reed, Lijo Joy, Edward Fogden, Kalisha Russell, Samia Hussain, Anne Phillips, Muaad Abdulla, Jeff Butterworth, Colene Adams, Mandy Carnahan, Elizabeth Buckingham, Danielle Childs, Alison Magness, Jo Stickley, Nichola Motherwell, Louise Tonks, Hannah Gibson, Kate Wistance, Caradog Thomas, Elaine Brinkworth, Lynda Connor, Amanda Cook, Tabitha Rees, Rachel Harford, Sean Farley, Marie Jones, Emma Wesley, Alison Moss, Jacob Lucas, Claire Lorimer, Maria Oleary, Maxine Dixon, Fiona Goodchild, Rebecca Twenlow, Corinne Pawley, Arvind Ramadas, Julie Tregonning, Olaku Okeke, Wendy Jackson, Ioannis Koumoutsos, Viji George, Swapna Kunhunny, Sophie Laverick, Isla Anderson, Sophie Smith, Joan Joyce, Sarala Janarthan, Kamal Patel, Mariam Ali, Hilda Mhandu, Aleem Rana, Katherine Spears, Joana Teixeira, Mark Mencias, Abigail Seaward, Jessica Sousa, Nooria Said, Mark Soomaroo, Valentina Raspa, Asha Tacouri, Nicholas Reps, Rebecca Martin, Tinashe Samakomva, Christian Selinger, Jenelyn Carbonell, Felicia Onovira, Doris Quartey, Alice L'Anson, Andrew Ashworth, Jessica Bailey, Angie Dunn, Gjuzel Bespaloi, Harold Rasalan, Zahid Mahmood, Racheal Campbell, Liane Marsh, Tricia Coughlan, Wisam Jafar, Janet Marrs, Christopher McPheat, Monira Rahman, Sarah Davies, Ruth Habibi, Ellen Jessup-Dunton, Teishel Joefield, Reina Layug, Vinod Patel, Joanne Vere, Victoria Turner, Susan Kilroy, Martina Coulding, Martyn Clark, Jacqueline McCormick, Attiya Nisar, Gareth Walker, Stacey Atkins, Jasmine Growdon, Becky George, Charlotte McNeill, Bryony Reed, Angela Foulds, Catherine Marshall, Michele Allison, Briony Dillon, Rachel Cooney, Lillie Bennett, Louise Bowlas, Sharafaath Shariff, Aileen Fraser, Dwayne Punnette, Rebecca Lambert, Charlotte Bishop-Hurman, Elizabeth Undrell, Katherine Belfield, Said Din, Catherine Addleton, Marie Appleby, Johanna Brown, Kathleen Holding, Catherine Fraser, Janice Birkenshaw, Jodie Williams, Kamille Maulion, Meg Lane, Arita Kravale, Claud Smith, Patricia Hooper, John deCaestecker, Olivia Watchorn, Ellie Clarke, Chris Hayward, Susan Inniss, Lucy Pritchard, Karen Rudge, Amanda Carney, Sarah Griffee, Jervoise Andreyev, Sathish Babu, Caroline Hayhurst, Carol Lockwood, Lynn Osborne, Amanda Roper, Karen Warner, Julia Hindle, Tara Lawrence, Kimberley Netherton, Caroline Watt, Kinga Szymiczek, Shameer Mehta, James Bell, William Blad, Lisa Whitley, Roman Jastrub, Dhamaraj Durai, Mark Baker, Elizabeth John Sivamurugan, Mim Evans, Fraser Cummings, Clare Harris, Amy Jones, Liga Krauze, Sohail Rahmany, Michelle Earl, Jenny Vowles, Audrey Torokwa, Mirela Petrova, Andrew Procter, Jo Stanley, Claudia Silvamoniz, Marion Bettey, Amar Wahid, Zoe Morrison, Rhian Thomas-Turner, Louise Yendle, Jennifer Muller, Marcus Mitchell, John Kirkwood, Anna Barnes, Rakesh Chaudhary, Melanie Claridge, Chiara Ellis, Cheryl Kemp, Ogwa Tobi, Jentus Milton, Emma Johnston, Metod Oblak, Carmen Winpenny, Marie-Louise Svensson, Jo Godden, Marium Ashhar, Debbie Alexander, Kate Covil, Lauranne Derikx, Sryros Siakavellas, Helen Baxter, Scott Robertson, Linda Smith, Beena Poulose, Anne Colemam, Margareta Balint, Gareth Rhys-Jones, Helen Watters, Susan Begg, Beatriz Grosalcalde, Judy Coyle, Kerrie Johns, Rachel Hughes, Janet Phipps, Abigail Taylor, Catherine MacPhee, Suzanne Brooks, Jolene John, Michelle Edwards, Katie Smith, Linda Howard, Dianne Wood, Ajay Muddu, Laura Barman, Janine Mallinson, Tania Neale, Diana Ionita, Kerry Elliot, Alison Turnball, Iola Thomas, Alice Thomas, Kelly Andrews, Jonathon Sutton, Caroline Mulvaney Jones, Julia Roberts, and Jeannie Bishop

Subjects
Hepatology, Gastroenterology, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5]
Abstract

Contains fulltext : 291657.pdf (Publisher’s version ) (Open Access) BACKGROUND: Anti-TNF drugs, such as infliximab, are associated with attenuated antibody responses after SARS-CoV-2 vaccination. We aimed to determine how the anti-TNF drug infliximab and the anti-integrin drug vedolizumab affect vaccine-induced neutralising antibodies against highly transmissible omicron (B.1.1.529) BA.1, and BA.4 and BA.5 (hereafter BA.4/5) SARS-CoV-2 variants, which possess the ability to evade host immunity and, together with emerging sublineages, are now the dominating variants causing current waves of infection. METHODS: CLARITY IBD is a prospective, multicentre, observational cohort study investigating the effect of infliximab and vedolizumab on SARS-CoV-2 infection and vaccination in patients with inflammatory bowel disease (IBD). Patients aged 5 years and older with a diagnosis of IBD and being treated with infliximab or vedolizumab for 6 weeks or longer were recruited from infusion units at 92 hospitals in the UK. In this analysis, we included participants who had received uninterrupted biological therapy since recruitment and without a previous SARS-CoV-2 infection. The primary outcome was neutralising antibody responses against SARS-CoV-2 wild-type and omicron subvariants BA.1 and BA.4/5 after three doses of SARS-CoV-2 vaccine. We constructed Cox proportional hazards models to investigate the risk of breakthrough infection in relation to neutralising antibody titres. The study is registered with the ISRCTN registry, ISRCTN45176516, and is closed to accrual. FINDINGS: Between Sept 22 and Dec 23, 2020, 7224 patients with IBD were recruited to the CLARITY IBD study, of whom 1288 had no previous SARS-CoV-2 infection after three doses of SARS-CoV-2 vaccine and were established on either infliximab (n=871) or vedolizumab (n=417) and included in this study (median age was 46·1 years [IQR 33·6-58·2], 610 [47·4%] were female, 671 [52·1%] were male, 1209 [93·9%] were White, and 46 [3·6%] were Asian). After three doses of SARS-CoV-2 vaccine, 50% neutralising titres (NT50s) were significantly lower in patients treated with infliximab than in those treated with vedolizumab, against wild-type (geometric mean 2062 [95% CI 1720-2473] vs 3440 [2939-4026]; p

Published
2023

13. A Rule-Based Acquisition Model Adapted for Morphological Analysis

Author

Lignos, Constantine, Chan, Erwin, Marcus, Mitchell P., Yang, Charles, Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Doug, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Peters, Carol, editor, Di Nunzio, Giorgio Maria, editor, Kurimo, Mikko, editor, Mandl, Thomas, editor, Mostefa, Djamel, editor, Peñas, Anselmo, editor, and Roda, Giovanna, editor

Published
2010
Full Text
View/download PDF

14. Decrease in Skin Prion-Seeding Activity of Prion-Infected Mice Treated with a Compound Against Human and Animal Prions: a First Possible Biomarker for Prion Therapeutics

Author

Mingxuan Ding, Wen-Quan Zou, Weiguanliu Zhang, Justin J. Greenlee, Hae Weon Lee, Jue Yuan, Kenta Teruya, Katsumi Doh-ura, Marcus Mitchell, Manuel V. Camacho, Li Cui, Ayumi Oguma, Aaron Foutz, and Qingzhong Kong

Subjects
0301 basic medicine, Gene isoform, Prion diseases, PrPSc Proteins, Prions, animal diseases, Transgene, Neuroscience (miscellaneous), Hamster, Mice, Transgenic, Scrapie, Biology, Article, Serial protein misfolding cyclic amplification (sPMCA), Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, TC-5RW, medicine, Animals, Skin, Brain, Chronic wasting disease, medicine.disease, Virology, In vitro, nervous system diseases, Biomarker, 030104 developmental biology, Neurology, Cellulose ethers, Real-time quaking-induced conversion (RT-QuIC), Protein Misfolding Cyclic Amplification, Biomarkers, 030217 neurology & neurosurgery
Abstract

Previous studies have revealed that the infectious scrapie isoform of prion protein (PrPSc) harbored in the skin tissue of patients or animals with prion diseases can be amplified and detected through the serial protein misfolding cyclic amplification (sPMCA) or real-time quaking-induced conversion (RT-QuIC) assays. These findings suggest that skin PrPSc-seeding activity may serve as a biomarker for the diagnosis of prion diseases; however, its utility as a biomarker for prion therapeutics remains largely unknown. Cellulose ethers (CEs, such as TC-5RW), widely used as food and pharmaceutical additives, have recently been shown to prolong the lifespan of prion-infected mice and hamsters. Here we report that in transgenic (Tg) mice expressing hamster cellular prion protein (PrPC) infected with the 263K prion, the prion-seeding activity becomes undetectable in the skin tissues of TC-5RW-treated Tg mice by both sPMCA and RT-QuIC assays, whereas such prion-seeding activity is readily detectable in the skin of untreated mice. Notably, TC-5RW exhibits an inhibitory effect on the in vitro amplification of PrPSc in both skin and brain tissues by sPMCA and RT-QuIC. Moreover, we reveal that TC-5RW is able to directly decrease protease-resistant PrPSc and inhibit the seeding activity of PrPSc from chronic wasting disease and various human prion diseases. Our results suggest that the level of prion-seeding activity in the skin may serve as a useful biomarker for assessing the therapeutic efficacy of compounds in a clinical trial of prion diseases and that TC-5RW may have the potential for the prevention/treatment of human prion diseases.

Published
2021

19. Characterization of Anchorless Human PrP With Q227X Stop Mutation Linked to Gerstmann-Sträussler-Scheinker Syndrome In Vivo and In Vitro

Author

Pingping Shen, Robert B. Petersen, Wen-Quan Zou, Yue Lang, Qingzhong Kong, Mingxuan Ding, Annemiek J.M. Rozemuller, Li Cui, Johnny Dang, Marcus Mitchell, Zerui Wang, Weiguanliu Zhang, Jue Yuan, Jiachun Feng, Pathology, and Amsterdam Neuroscience - Neurodegeneration

Subjects
Adult, 0301 basic medicine, Gene isoform, Protein Folding, Glycosylation, Gerstmann-Sträussler-Scheinker (GSS) syndrome, Prions, animal diseases, Mutant, Prion disease, Neuroscience (miscellaneous), Mice, Transgenic, Protein misfolding cyclic amplification (PMCA), Glycosylphosphatidylinositol (GPI) anchor, medicine.disease_cause, Antibodies, Article, Protein Aggregates, 03 medical and health sciences, Cellular and Molecular Neuroscience, Allelic origin, 0302 clinical medicine, Cell Line, Tumor, Centrifugation, Density Gradient, medicine, Animals, Gerstmann-Straussler-Scheinker Disease, Humans, Mutation, Chemistry, Cell Membrane, Brain, Transfection, medicine.disease, Gerstmann–Sträussler–Scheinker syndrome, Molecular biology, In vitro, nervous system diseases, Blot, 030104 developmental biology, Prion protein, Neurology, Codon, Nonsense, Protein Misfolding Cyclic Amplification, Female, Autopsy, 030217 neurology & neurosurgery
Abstract

Alteration in cellular prion protein (PrPC) localization on the cell surface through mediation of the glycosylphosphatidylinositol (GPI) anchor has been reported to dramatically affect the formation and infectivity of its pathological isoform (PrPSc). A patient with Gerstmann-Sträussler-Scheinker (GSS) syndrome was previously found to have a nonsense heterozygous PrP-Q227X mutation resulting in an anchorless PrP. However, the allelic origin of this anchorless PrPSc and cellular trafficking of PrPQ227X remain to be determined. Here, we show that PrPSc in the brain of this GSS patient is mainly composed of the mutant but not wild-type PrP (PrPWt), suggesting pathological PrPQ227X is incapable of recruiting PrPWt in vivo. This mutant anchorless protein, however, is able to recruit PrPWt from humanized transgenic mouse brain but not from autopsied human brain homogenates to produce a protease-resistant PrPSc-like form in vitro by protein misfolding cyclic amplification (PMCA). To further investigate the characteristics of this mutation, constructs expressing human PrPQ227X or PrPWt were transfected into neuroblastoma cells (M17). Fractionation of the M17 cells demonstrated that most PrPWt is recovered in the cell lysate fraction, while most of the mutant PrPQ227X is recovered in the medium fraction, consistent with the results obtained by immunofluorescence microscopy. Two-dimensional gel-electrophoresis and Western blotting showed that cellular PrPQ227X spots clustered at molecular weights of 22–25 kDa with an isoelectric point (pI) of 3.5–5.5, whereas protein spots from the medium are at 18–26 kDa with a pI of 7–10. Our findings suggest that the role of GPI anchor in prion propagation between the anchorless mutant PrP and wild-type PrP relies on the cellular distribution of the protein.

Published
2021

22. The effect of health insurance coverage and the doctor-patient relationship on health care utilization in high poverty neighborhoods

Author

Marcus Mitchell, Andrea Hudson, Kenneth Hudson, Destini A. Smith, Marcellus Hudson, Alan Akira, and Errol D. Crook

Subjects
lcsh:Medicine, Health Informatics, Disease, Odds, 03 medical and health sciences, 0302 clinical medicine, Health insurance, Preventative care, Diabetes mellitus, Environmental health, Health care, medicine, 030212 general & internal medicine, Socioeconomic status, 030505 public health, business.industry, Minority health, lcsh:R, 1. No poverty, Public Health, Environmental and Occupational Health, Regular Article, medicine.disease, Health equity, 3. Good health, Usual provider, Hypertension, Screening, Doctor–patient relationship, Cluster sampling, Health disparities, 0305 other medical science, business
Abstract

African Americans have higher rates of mortality than whites who are the same age and sex. We hypothesize that in low socioeconomic status neighborhoods, having health insurance coverage and a regular health care provider increases the likelihood of receiving diagnostic tests for cardiovascular disease and diabetes. We use data from a random two-stage cluster sample of 230 adults living in high poverty census tracts to examine the effects of insurance coverage and having a regular doctor on the likelihood receiving diagnostic tests for high cholesterol, high blood sugar, and blood pressure. We find that health insurance coverage increases the odds of having a regular health care provider (p, Highlights • The effect of health insurance on testing for cardiovascular disease is examined. • Health insurance increases the odds of being tested. • Having a regular health care provider mediates the effect of insurance on testing. • The mediation is greatest when the patient can report the doctor's name.

Published
2017

24. AAAI Fall Symposium reports

Author

Ball, Jerry, Arney, Chris, Collins, Samuel G., Marcus, Mitchell, Nirenburg, Sergei Chella, Antonio, Goebel, Kai, Li, Jason, Lyell, Margaret, Magerko, Brian, Manzotti, Riccardo, Morrison, Clayton T., Oates, Tim, Riedl, Mark, Trajkovski, Goran P., Truszkowski, Walt, and Uckun, Serdar

Subjects
Artificial intelligence, Technology application, Artificial intelligence -- Innovations, Consciousness -- Technology application
Abstract

AI and Consciousness: Theoretical Foundations and Current Approaches Is it possible to build a conscious machine? Is trying to design and build a conscious machine helpful to understanding the nature […], The Association for the Advancement of Artificial Intelligence presented the 2007 Fall Symposium Series on Friday through Sunday, November 9-11, at the Westin Arlington Gateway, Arlington, Virginia. The titles of the seven symposia were (1) AI and Consciousness: Theoretical Foundations and Current Approaches, (2) Artificial Intelligence for Prognostics, (3) Cognitive Approaches to Natural Language Processing, (4) Computational Approaches to Representation Change during Learning and Development, (5) Emergent Agents and Socialities: Social and Organizational Aspects of Intelligence, (6) Intelligent Narrative Technologies, and (7) Regarding the "Intelligence" in Distributed Intelligent Systems.

Published
2008

26. Fixed versus sun tracking solar panels: an economic analysis

Author

Zaid Almusaied, Andrew Bland, Eric Leake, Semih Aslan, Kyle Rainosek, Heejoo Lee, Jesus Fuentes, Marcus Mitchell, Nicholas Hawkes, and Bahram Asiabanpour

Subjects
Economics and Econometrics, Environmental Engineering, Data collection, Meteorology, business.industry, BitTorrent tracker, Sun tracking, 020209 energy, Photovoltaic system, 02 engineering and technology, Management, Monitoring, Policy and Law, 021001 nanoscience & nanotechnology, Solar energy, General Business, Management and Accounting, Solar tracker, Data acquisition, 0202 electrical engineering, electronic engineering, information engineering, Environmental Chemistry, Environmental science, 0210 nano-technology, business, Intensity (heat transfer), Remote sensing
Abstract

The performance of photovoltaic panels depends on many factors. One factor involves the light reception angles at the panels in which the intensity of the received solar radiation from the sun at the earth is affected significantly by the diurnal and seasonal movement of the earth. The maximum output of the panels is achieved when the panels are perpendicular to the sun’s rays. This research is an empirical financial assessment of the benefit of using a dual-axis sun tracker versus a fixed-flat position, as well as a comparison of the performance of the two panels under such settings. The experiment was conducted using 190 W panels, a manual dual-axis sun tracker, and a data acquisition system, which collected and stored the experimental data. A significant improvement in output was noticed in the tracked panel. The overall average improvement for the entire data collection time interval was 82 %. The financial assessment was performed based on the energy market rate in Texas and the average price and operative expenses of the dual-axis sun trackers. The breakeven point for the dual-axis sun tracking system was found to be “never,” 13, and 6 years for 1-, 4-, and 9-panel configurations, respectively, in each system.

Published
2016

30. Gene expression markers of age-related inflammation in two human cohorts

Author

Lorna W. Harries, Andrew B. Singleton, Joanne M. Murabito, Luigi Ferrucci, Kathryn L. Lunetta, Dena G. Hernandez, Luke C. Pilling, Peter J. Munson, Honghuang Lin, David Melzer, Sai Xia Ying, William Henley, Emelia J. Benjamin, Daniel Levy, Josée Dupuis, Marcus Mitchell, and Roby Joehanes

Subjects
Adult, Genetic Markers, Male, Aging, Inflammation, Biochemistry, Article, Transcriptome, Cohort Studies, Endocrinology, Framingham Heart Study, Gene expression, Genetics, medicine, Cytotoxic T cell, Humans, Molecular Biology, Gene, Aged, Aged, 80 and over, biology, Interleukin-6, Gene Expression Profiling, Confounding, Cell Biology, Middle Aged, Perforin, Immunology, biology.protein, Female, medicine.symptom, Inflammation Mediators, Biomarkers
Abstract

Introduction Chronically elevated circulating inflammatory markers are common in older persons but mechanisms are unclear. Many blood transcripts (> 800 genes) are associated with interleukin-6 protein levels (IL6) independent of age. We aimed to identify gene transcripts statistically mediating, as drivers or responders, the increasing levels of IL6 protein in blood at older ages. Methods Blood derived in-vivo RNA from the Framingham Heart Study (FHS, n = 2422, ages 40–92 yrs) and InCHIANTI study (n = 694, ages 30–104 yrs), with Affymetrix and Illumina expression arrays respectively (> 17,000 genes tested), were tested for statistical mediation of the age-IL6 association using resampling techniques, adjusted for confounders and multiple testing. Results In FHS, IL6 expression was not associated with IL6 protein levels in blood. 102 genes (0.6% of 17,324 expressed) statistically mediated the age-IL6 association of which 25 replicated in InCHIANTI (including 5 of the 10 largest effect genes). The largest effect gene ( SLC4A10 , coding for NCBE, a sodium bicarbonate transporter) mediated 19% (adjusted CI 8.9 to 34.1%) and replicated by PCR in InCHIANTI (n = 194, 35.6% mediated, p = 0.01). Other replicated mediators included PRF1 (perforin, a cytolytic protein in cytotoxic T lymphocytes and NK cells) and IL1B (Interleukin 1 beta): few other cytokines were significant mediators. Conclusions This transcriptome-wide study on human blood identified a small distinct set of genes that statistically mediate the age-IL6 association. Findings are robust across two cohorts and different expression technologies. Raised IL6 levels may not derive from circulating white cells in age related inflammation.

Published
2014

39. Wait-and-See Strategies for Parsing Natural Language

Author

Marcus, Mitchell P. and Marcus, Mitchell P.

Abstract

Work reported herein was conducted at the Artificial Intelligence Laboratory, a Massachusetts Institute of Technology research program supported in part by the Advanced Research Projects Agency of the Department of Defense and monitored by the Office of Naval Research under Contract Number N00014-70-A-0362-0005., The intent of this paper is to convey one idea central to the structure of a natural language parser currently under development, the notion of wait-and-see strategies. This notion will hopefully allow the recognition of the structure of natural language input by a process that is deterministic and "backupless", that can have strong expectations but still be immediately responsive to the actual structure of the input. The notion is also discussed as a paradigm for recognition processes in general., MIT Artificial Intelligence Laboratory

Published
2008

40. A theory of syntactic recognition for natural language.

Author

Jonathan Allen., Massachusetts Institute of Technology. Dept. of Electrical Engineering and Computer Science, Marcus, Mitchell Philip, Jonathan Allen., Massachusetts Institute of Technology. Dept. of Electrical Engineering and Computer Science, and Marcus, Mitchell Philip

Abstract

Thesis. 1978. Ph.D.--Massachusetts Institute of Technology. Dept. of Electrical Engineering and Computer Science., MICROFICHE COPY AVAILABLE IN ARCHIVES AND ENGINEERING., Bibliography: p. 331-335., Ph.D.

Published
2005

41. An Overview of a Theory of Syntactic Recognition for Natural Language

Author

Marcus, Mitchell P. and Marcus, Mitchell P.

Abstract

Assume that the syntax of natural language can be parsed by a left-to-right deterministic mechanism without facilities for parallelism or backup. It will be shown that this "determinism" hypothesis, explored within the context of the grammar of English, leads to a simple mechanism, a grammar interpreter, having the following properties: (a) Simple rules of grammar can be written for this interpreter which capture the generalizations behind various linguistic phenomena, despite the seeming difficulty of capturing such generalizations in the framework of a processing model for recognition. (b) The structure of the grammar rules cannot parse sentences which violate either of two constraints which Chomsky claims are linguistic universals. This result depends in part upon the computational use of Chomsky's notion of Annotated Surface Structure. (c) The grammar interpreter provides a simple explanation for the difficulty caused by "garden path" sentences, such as "The cotton clothing is made of grows in Mississippi". To the extent that these properties, all of which reflect deep properties of natural language, follow from the original hypothesis, they provide indirect evidence for the truth of this assumption. This memo is an abridged form of several topics discussed at length in [Marcus 77]; it does not discuss the mechanism used to parse noun phrases nor the kinds of interaction between syntax and semantics discussed in that work.

Published
2004

42. Treebank-3

Author

Marcus, Mitchell, Santorini, Beatrice, Marcinkiewicz, Mary Ann, Taylor, Ann, Marcus, Mitchell, Santorini, Beatrice, Marcinkiewicz, Mary Ann, and Taylor, Ann

Abstract

*Introduction* This CD-ROM contains the following Treebank-2 Material: * One million words of 1989 Wall Street Journal material annotated in Treebank II style. * A small sample of ATIS-3 material annotated in Treebank II style. * A fully tagged version of the Brown Corpus. and the following new material: * Switchboard tagged, dysfluency-annotated, and parsed text * Brown parsed text The Treebank bracketing style is designed to allow the extraction of simple predicate/argument structure. Over one million words of text are provided with this bracketing applied. *Data* The Penn Treebank (PTB) project selected 2,499 stories from a three year Wall Street Journal (WSJ) collection of 98,732 stories for syntactic annotation. These 2,499 stories have been distributed in both Treebank-2 (LDC1999T42) and Treebank-3 (LDC1999T42) releases of PTB. Treebank-2 includes the raw text for each story. Three map files are available in a compressed file via ftp and provide the relation between the 2,499 PTB filenames and the corresponding WSJ DOCNO strings in TIPSTER. *Updates* After publication, it was discovered that not all of the postscript (*.ps) files had been converted to pdfs and that some of the converted pdfs contained errors. For pdf copies of the documentation files, please go to addenda for a list of the files available.

Published
1999

43. OntoNotes

Author

Hovy, Eduard, primary, Marcus, Mitchell, additional, Palmer, Martha, additional, Ramshaw, Lance, additional, and Weischedel, Ralph, additional

Published
2006
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46. The benefits of charitable giving

Author

Marcus, Mitchell

Subjects
Philanthropy, Charities, Charitable contributions, General interest, News, opinion and commentary
Abstract

Byline: Marcus, Mitchell The benefits of charitable giving Our communities, our families, and we ourselves are often touched personally by the benefits provided by religious and charitable organizations. In times [...]

Published
1999

47. Treebank-2

Author

Marcus, Mitchell, Santorini, Beatrice, Marcinkiewicz, Mary Ann, Marcus, Mitchell, Santorini, Beatrice, and Marcinkiewicz, Mary Ann

Abstract

Original release was: LDC Catalog No.: LDC94T4B-3.1 NIST Catalog No.: NA LDC Release date: 4/94 (MY94) Original Treebank Release This CD-ROM contains over 1.6 million words of hand-parsed material from the Dow Jones News Service, plus an additional one million words tagged for part-of-speech. This material is a subset of the language model corpus for the DARPA CSR large-vocabulary speech recognition project. It also contains the first fully parsed version of the Brown Corpus, which has also been completely retagged using the Penn Treebank (PTB) tag set. Also included are tagged and parsed data from Department of Energy abstracts, IBM computer manuals, MUC-3 and ATIS. In addition, the CD-ROM includes source code for programs that were used by the PTB project in creating portions of the data. Source code is also included for "tgrep," a program that permits the user to search for specific constituents in tree structures. All software is provided "as is." (We have learned since publication that the tgrep source code provided on the cd-rom is not readily portable, and compiling tgrep requires modification of the source files. The CD-ROM does include a pre-compiled program file for tgrep, built for use on Sun sparc systems.) Release - 2 The PTB Project Release 2 CD-ROM features the new PTB-2 bracketing style, which is designed to allow the extraction of simple predicate/argument structure. Over one million words of text are provided with this bracketing applied, along with a complete style manual explaining the bracketing and new versions of tools for searching and treating bracketed data. This CD-ROM also contains all the annotated text material from the earlier Treebank Preliminary Release, including the Brown Corpus. While these materials have not all been converted to the newer bracketing style, they have been cleaned up to remove problems that had appeared in the earlier release. The contents of Treebank Release 2 are as follows: * One million words of 1989 Wall Stre

Published
1995

49. Automatically Acquiring Phrase Structure Using Distributional Analysis

Author

PENNSYLVANIA UNIV PHILADELPHIA, Brill, Eric, Marcus, Mitchell, PENNSYLVANIA UNIV PHILADELPHIA, Brill, Eric, and Marcus, Mitchell

Abstract

In this paper, we present evidence that the acquisition of the phrase structure of a natural language is possible without supervision and with a very small initial grammar. We describe a language learner that extracts distributional information from a corpus annotated with parts of speech and is able to use this extracted information to accurately parse short sentences. The phrase structure learner is part of an ongoing project to determine just how much knowledge of language can be learned solely through distributional analysis.

Published
1992

50. Parsing the Voyager Domain Using Pearl

Author

PENNSYLVANIA UNIV PHILADELPHIA DEPT OF COMPUTER AND INFORMATION SCIENCE, Magerman, David M., Marcus, Mitchell P., PENNSYLVANIA UNIV PHILADELPHIA DEPT OF COMPUTER AND INFORMATION SCIENCE, Magerman, David M., and Marcus, Mitchell P.

Abstract

This paper describes a natural language parsing algorithm for unrestricted text which uses a probability-based scoring function to select the "best" parse of a sentence according to a given grammar. The parser, Pearl, is a time-asynchronous bottom-up chart parser with Earley-type lop-down prediction which pursues the highest-scoring theory in the chart, where the score of a theory represents the extent to which the context of the sentence predicts that interpretation. This parser differs from previous attempts at stochastic parsers in that it uses a richer form of conditional probabilities based on context to predict likelihood. Pearl also provides a framework for incorporating the results of previous work in part-of-speech assignment, unknown word models, and other probabilistic models of linguistic features in one parsing tool, interleaving these techniques instead of using the traditional pipeline architecture. In tests performed on the Voyager direction-finding domain, Pearl has been successful at resolving part-of-speech ambiguity, determining categories for unknown words, and selecting correct parses first using a very loosely fitting covering grammar., Sponsored in part by AFOSR Grant no. AFOSR-90-0066 and ARO Grant no. DAAL03-89-C-0031PR1. Presented at the Human Language Technology Conference held in Pacific Grove, CA on 19-22 Feb 1991 and published in proceedings of the Speech and Natural Language Workshop, p231-236. ISBN 1-55860-207-0.

Published
1991

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