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1,013 results on '"Gell P"'

1. The Klein-Gordon equation on asymptotically Minkowski spacetimes: causal propagators

Author

Baskin, Dean, Doll, Moritz, and Gell-Redman, Jesse

Subjects
Mathematics - Analysis of PDEs, Mathematical Physics
Abstract

We construct the causal (forward/backward) propagators for the massive Klein-Gordon equation perturbed by a first order operator which decays in space but not necessarily in time. In particular, we obtain global estimates for forward/backward solutions to the inhomogeneous, perturbed Klein-Gordon equation, including in the presence of bound states of the limiting spatial Hamiltonians. To this end, we prove propagation of singularities estimates in all regions of infinity (spatial, null, and causal) and use the estimates to prove that the Klein-Gordon operator is an invertible mapping between adapted weighted Sobolev spaces. This builds off work of Vasy in which inverses of hyperbolic PDEs are obtained via construction of a Fredholm mapping problem using radial points propagation estimates. To deal with the presence of a perturbation which persists in time, we employ a class of pseudodifferential operators first explored in Vasy's many-body work., Comment: 95 pages, 6 figures

Published
2024

2. Wetland management: preparing for climate and coastal change using adaptation pathways

Author

Gell Peter

Subjects
Environmental sciences, GE1-350
Abstract

Freshwater ecosystems are among the most threatened in the world. The list of threatened species in freshwater ecosystems is greater than that in terrestrial or marine systems and freshwater vertebrates are particularly at risk. Freshwater wetlands have evolved in coastal zones protected from tidal influence by barrier dune systems. Similarly, estuaries have supported zones of low salinity diluted by flows from land, but water resource development has limited these flows and driven ecological change in estuarine systems. These historical uses of river flows, and the impacts of catchment development on water quality and yields, have combined to threaten coastal wetland ecosystems. They are now under increasing threat through climate change driven alterations to hydroclimatic conditions, as well an rising sea levels which risk inundation of low lying coastal regions, including wetlands. Coastal freshwater systems offer considerable ecosystem services to human systems and host significant biodiversity assets. These have been subjected to increased risk through catchment and coastal development, but are now acutely threatened through changed river flows and elevated sea levels that result from climate change. Managing these systems requires an adaptation pathways approach that accommodates human needs, and society’s obligations to global biodiversity.

Published
2020
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4. Scattering regularity for small data solutions of the nonlinear Schr\'{o}dinger equation

Author

Gell-Redman, Jesse, Gomes, Sean, and Hassell, Andrew

Subjects
Mathematics - Analysis of PDEs, Mathematical Physics, 35Q55 (Primary) 35P25, 58J47 (Secondary)
Abstract

Using the Fredholm theory of the linear time-dependent Schr\"odinger equation set up in our previous article arXiv:2201.03140, we solve the final-state problem for the nonlinear Schr\"odinger problem $$ (D_t + \Delta + V) u = N[u], \quad u(z,t) \sim (4\pi it)^{-n/2} e^{i|z|^2/4t} f\big( \frac{z}{2t} \big), \quad t \to -\infty, $$ where $u : \mathbb{R}^{n+1} \to \mathbb{C}$ is the unknown and $f : \mathbb{R}^n \to \mathbb{C}$ is the asymptotic data. Here $D_t = -i \frac{\partial}{\partial t}$ and $\Delta = \sum_{j=1}^n D_{z_j} D_{z_j}$ is the positive Laplacian, or more generally a compactly supported, nontrapping perturbation of this, $V$ is a smooth compactly supported potential function, and the nonlinear term $N$ is a (suitable) polynomial in $u$, $\partial_{z_j}u$ and their complex conjugates satisfying phase invariance. Our assumption on the asymptotic data $f$ is that it is small in a certain function space $\mathcal{W}^k$ constructed in arXiv:2201.03140, for sufficiently large $k \in \mathbb{N}$, where the index $k$ measures both regularity and decay at infinity (it is similar to, but not quite a standard weighted Sobolev space $H^{k, k}(\mathbb{R}^n)$). We find that for $N[u] = \pm |u|^{p-1} u$, $p$ odd, and $(n,p) \neq (1, 3)$ then if the asymptotic data as $t \to -\infty$ is small in $\mathcal{W}^k$, then the asymptotic data as $t \to +\infty$ is also in $\mathcal{W}^k$; that is, the nonlinear scattering map preserves these spaces of asymptotic data. For a more general nonlinearity involving derivatives of $u$, we show that if the asymptotic data as $t \to -\infty$ is small in $\langle \zeta \rangle^{-1} \mathcal{W}^k_\zeta$, then the asymptotic data as $t \to +\infty$ is also in this space (where $\zeta$ is the argument of $f$)., Comment: 48 pages, 2 figures

Published
2023

6. Management to Insulate Ecosystem Services from the Effects of Catchment Development

Author

Gell Peter

Subjects
Environmental sciences, GE1-350
Abstract

Natural ecosystems provide amenity to human populations in the form of ecosystem services. These services are grouped into four broad categories: provisioning – food and water production; regulating – control of climate and disease; supporting – crop pollination; and cultural – spiritual and recreational benefits. Aquatic systems provide considerable service through the provision of potable water, fisheries and aquaculture production, nutrient mitigation and the psychological benefits that accrue from the aesthetic amenity provided from lakes, rivers and other wetlands. Further, littoral and riparian ecosystems, and aquifers, protect human communities from sea level encroachment, and tidal and river flooding. Catchment and water development provides critical resources for human consumption. Where these provisioning services are prioritized over others, the level and quality of production may be impacted. Further, the benefits from these provisioning services comes with the opportunity cost of diminishing regulating, supporting and cultural services. This imbalance flags concerns for humanity as it exceeds recognised safe operating spaces. These concepts are explored by reference to long term records of change in some of the world’s largest river catchments and lessons are drawn that may enable other communities to consider the balance of ecosystems services in natural resource management.

Published
2018
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8. Physical therapy for survivors of torture: A scoping review

Author

Justine McCuen Dee, Nancy Gell, Constance van Eeghen, and Benjamin Littenberg

Subjects
Medicine, Social sciences (General), H1-99
Abstract

Background: Torture can result in impaired function, reduced quality of life, and chronic pain. Physical therapy (PT) is recommended for wholistic care of survivors of torture (SOT), however there are limited evidenced-based guidelines. We conducted a scoping review to identify and describe the approach and gaps in knowledge around the PT treatment of SOT.Methods: We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Nine databases were searched from inception to 2023. Eligible sources were those involving PT treatment for SOT. Extracted data included the source of evidence, PT description, mode of delivery, and research study outcomes. Interventions were categorized into themes based on recommendations from the Physiotherapy and Refugees Education Project: trauma-informed care, body-awareness and empowerment, and pain management. Source-reported treatment approach and expected effect of the interventions informed the thematic categorization.Results: The final analysis included thirteen sources with a combined total of 18 different interventions. Thematically, two sources described interventions targeting body-awareness and empowerment, while five sources targeted body-awareness and empowerment and pain management. Six sources included all three themes. Two of these six sources were research studies examining PT outcomes. Findings were significant favoring the PT, but results must be taken cautiously due to methodological limitations. Studies assessing treatment related to only one theme resulted in no between group differences. Conclusions: We describe the scope of the literature regarding PT for SOT. A trauma-informed PT approach, coordinated with pain management, and body-awareness and empowerment interventions may address the complex needs of survivors. However, rigorous studies of this approach are lacking. As the number of displaced persons continues to rise globally, we must be prepared to care for these vulnerable people. Physical therapists are encouraged to utilize a wholistic approach, and to examine outcomes of this approach for survivors of torture.

Published
2024
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9. Price's law on Minkowski space in the presence of an inverse square potential

Author

Baskin, Dean, Gell-Redman, Jesse, and Marzuola, Jeremy L.

Subjects
Mathematics - Analysis of PDEs, 35L05, 35Q41, 35L81
Abstract

We consider the pointwise decay of solutions to wave-type equations in two model singular settings. Our main result is a form of Price's law for solutions of the massless Dirac-Coulomb system in (3+1)-dimensions. Using identical techniques, we prove a similar theorem for the wave equation on Minkowski space with an inverse square potential. One novel feature of these singular models is that solutions exhibit two different leading decay rates at timelike infinity in two regimes, distinguished by whether the spatial momentum along a curve which approaches timelike infinity is zero or non-zero. An important feature of our analysis is that it yields a precise description of solutions at the interface of these two regions which comprise the whole of timelike infinity., Comment: 14 pages, 2 figures; version 2: significant revisions, emphasized Dirac-Coulomb application and clarified exposition

Published
2022

10. Caregiver Characteristics and Barriers to Resource Use: Findings From a Rural State Caregiver Survey

Author

Maija Reblin PhD, Nancy Gell PT, PhD, MPH, Kelly Melekis PhD, and Christine M. Proulx

Subjects
Geriatrics, RC952-954.6
Abstract

Background: Despite the key role family caregivers play in the US healthcare system, they are not systematically identified and tracked, limiting our knowledge about this important group. Objective: Our objective was to identify caregiver characteristics and barriers to service delivery in a primarily rural state. Methods: As part of a quality improvement project, a cross-sectional online survey was fielded in clinical and community settings. Participants included 85 self-identified adult caregivers of another adult with an illness, condition, or disability from within a US state healthcare network. Descriptive analyses were conducted, and inferential statistics were used to compare urban versus rural respondents and older versus younger respondents. Results: Caregivers were responsible for a wide range of care activities and particularly older caregivers spent a significant amount of time providing care. Older caregivers also reported significantly lower levels of burden compared to younger caregivers, yet both groups had clinically high levels on average. Caregivers reported receiving helpful emotional support, but needed more tangible support and were limited by availability and cost. Conclusions: There is a need to fund comprehensive caregiver programing and address caregivers’ own social and physical health needs to reduce caregiver burden.

Published
2024
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11. Faculty Training on Navigating Gender and Sex in Medical Education

Author

Benjamin Crosby, Hannah Dumas, Janet Monroe, Fredric Fabiano, Isabelle Gell-Levey, Christopher Noyes, Kikuye Sugiyama, Jennifer Siegel, Angelique Harris, Carl Streed, and Ann C. Zumwalt

Subjects
Gender and Sexual Diversity, Sexual and Gender Minorities, Clinical Reasoning/Diagnostic Reasoning, Cultural Competence, Differences of Sexual Development, Faculty Development, Medicine (General), R5-920, Education
Abstract

Introduction Language that assumes gender and sex are binary and aligned is pervasive in medicine and is often used when teaching on physiology and pathology. Information presented through this lens oversimplifies disease mechanisms and poorly addresses the health of gender and sexually diverse (GSD) individuals. We developed a training session to help faculty reference gender and sex in a manner that would be accurate and inclusive of GSD health. Methods The 1-hour session for undergraduate and graduate medical educators highlighted cisgender and binary biases in medical teachings and introduced a getting-to-the-root mindset that prioritized teaching the processes underlying differences in disease profiles among gender and sex subpopulations. The training consisted of 30 minutes of didactic teaching and 20 minutes of small-group discussion. Medical education faculty attended and self-reported knowledge and awareness before and after the training. Results were compared using paired t tests. Expenses included fees for consultation and catering. Results Forty faculty participated (pretraining survey n = 36, posttraining survey n = 21). After the training, there was a significant increase in self-reported awareness of the difference between gender and sex (p = .002), perceived relevance of gender to teachings (p = .04), and readiness to discuss physiological drivers of sex-linked disease (p = .005). Discussion Participants reported increased understanding and consideration of gender and sex in medical education; feedback emphasized a desire for continued guidance. This easily adaptable session can provide an introduction to a series of medical teachings on gender and sex.

Published
2024
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12. Training in basic clinical ultrasound for intensive care physicians as professional improvement strategy

Author

Rebeca Iracema Delgado Fernández, Anabel Hernández, Teresa de la Caridad Pérez Díaz, Ivon Zoila Navarrete Baldassarri, and David Valdés-Ávila Gell

Subjects
atención al paciente, métodos, ultrasonografía., Medicine, Medicine (General), R5-920
Abstract

Introduction: Clinical ultrasound has provided notable benefits in terms of effectiveness, responsiveness, objective decisions and more beneficial actions for seriously ill patients. Objective: To evaluate a training as a strategy for professional improvement, to increase professional performance in the specific competencies of basic clinical ultrasound, of intensivist doctors. Methods: A participatory action research was carried out. The dependent variable was professional performance in the specific competencies of basic clinical ultrasound and the independent variable was training in basic Point-of-care Ultrasound (POCUS). The McNemar test was used to identify changes in professional performance; A confidence level of 99% was set, with significance level α= 0.01. Iadov's logical table was applied to calculate the group satisfaction index with the training. Results: In the cognitive (knowledge) and procedural (skills) dimensions, the greatest positive, statistically significant changes were seen, mainly in the knowledge for measuring the diameter of the optic nerve sheath and to a lesser extent, the knowledge about basic echocardiography. Improvement was identified in 13 of the 15 compared indicators (88.2%). The participants evaluated the training as satisfactory. Conclusions: Training, as a professional improvement strategy, increases performance in specific competencies in basic clinical ultrasound.

Published
2024

13. Pediatric Tumors as Disorders of Development: The Case for In Vitro Modeling Based on Human Stem Cells

Author

Cullen D. Clairmont, Joanna J. Gell, and Ching C. Lau

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Despite improvements in patient outcomes, pediatric cancer remains a leading cause of non-accidental death in children. Recent genetic analysis of patients with pediatric cancers indicates an important role for both germline genetic predisposition and cancer-specific somatic driver mutations. Increasingly, evidence demonstrates that the developmental timepoint at which the cancer cell-of-origin transforms is critical to tumor identity and therapeutic response. Therefore, future therapeutic development would be bolstered by the use of disease models that faithfully recapitulate the genetic context, cell-of-origin, and developmental window of vulnerability in pediatric cancers. Human stem cells have the potential to incorporate all of these characteristics into a pediatric cancer model, while serving as a platform for rapid genetic and pharmacological testing. In this review, we describe how human stem cells have been used to model pediatric cancers and how these models compare to other pediatric cancer model modalities.

Published
2024
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14. 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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15. Propagation of singularities and Fredholm analysis for the time-dependent Schr\'odinger equation

Author

Gell-Redman, Jesse, Gomes, Sean, and Hassell, Andrew

Subjects
Mathematics - Analysis of PDEs, Mathematics - Spectral Theory, 35Q41 (Primary) 35P25, 58J47 (Secondary)
Abstract

We study the time-dependent Schr\"odinger operator $P = D_t + \Delta_g + V$ acting on functions defined on $\mathbb{R}^{n+1}$, where, using coordinates $z \in \mathbb{R}^n$ and $t \in \mathbb{R}$, $D_t$ denotes $-i \partial_t$, $\Delta_g$ is the positive Laplacian with respect to a time dependent family of non-trapping metrics $g_{ij}(z, t) dz^i dz^j$ on $\mathbb{R}^n$ which is equal to the Euclidean metric outside of a compact set in spacetime, and $V = V(z, t)$ is a potential function which is also compactly supported in spacetime. In this paper we introduce a new approach to studying $P$, by finding pairs of Hilbert spaces between which the operator acts invertibly. Using this invertibility it is straightforward to solve the `final state problem' for the time-dependent Schr\"odinger equation, that is, find a global solution $u(z, t)$ of $Pu = 0$ having prescribed asymptotics as $t \to \infty$. These asymptotics are of the form $$ u(z, t) \sim t^{-n/2} e^{i|z|^2/4t} f_+\big( \frac{z}{2t} \big), \quad t \to +\infty $$ where $f_+$, the `final state' or outgoing data, is an arbitrary element of a suitable function space $\mathcal{W}^k(\mathbb{R}^n)$; here $k$ is a regularity parameter simultaneously measuring smoothness and decay at infinity. We can of course equally well prescribe asymptotics as $t \to -\infty$; this leads to incoming data $f_-$. We consider the `Poisson operators' $\mathcal{P}_\pm : f_\pm \to u$ and precisely characterize the range of these operators on $\mathcal{W}^k(\mathbb{R}^n)$ spaces. Finally we show that the scattering matrix, mapping $f_-$ to $f_+$, preserves these spaces., Comment: 63 pages, 3 figures

Published
2022

16. Comparison of faculty and student perceptions of sexual and gender minority content in a preclerkship medical curriculum

Author

Benjamin Crosby, Isabelle M. Gell-Levey, Janet Monroe, Carl G. Streed, Jennifer Siegel, Erin E. Carter, Nat Mulkey, and Ann C. Zumwalt

Subjects
Undergraduate medical education, Sexual and gender minorities, Curriculum assessment, Sexual orientation, Gender identity, LGBTQ +, Special aspects of education, LC8-6691, Medicine
Abstract

Abstract Background Sexual and gender minority (SGM) persons experience stark health disparities. Efforts to mitigate disparities through medical education have met some success. However, evaluations have largely focused on subjective perspectives rather than objective measures. This study aimed to quantify Boston University School of Medicine’s sexual and gender minority (SGM) education through surveys of course directors (CDs) and medical students regarding where SGM topics were taught in the preclerkship medical curriculum. Responses were compared to identify concordance between faculty intention and student perceptions regarding SGM education. Methods A cross-sectional survey was distributed to preclerkship CDs and current medical students in Spring 2019 and 2021, respectively, regarding where in the mandatory preclerkship curriculum CDs deliberately taught and where first- and second-year students recalled having learned 10 SGM topic domains. Results 64.3% of CDs (n = 18), 47.0% of the first-year class (n = 71), and 67.3% of the second-year class (n = 101) responded to the surveys. Results indicate that, as anticipated, deliberate SGM teaching correlates with greater student recall as students recalled topics that were reported by CDs as intentionally taught at a significantly higher rate compared to those not intentionally taught (32.0% vs. 15.3%; p

Published
2023
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17. Asymptotics of the radiation field for the massless Dirac-Coulomb system

Author

Baskin, Dean, Booth, Robert, and Gell-Redman, Jesse

Subjects
Mathematics - Analysis of PDEs, 58J47, 35Q41
Abstract

We consider the long-time behavior of the massless Dirac equation coupled to a Coulomb potential. For nice enough initial data, we find a joint asymptotic expansion for solutions near the null and future infinities and characterize explicitly the decay rates seen in the expansion. This paper can be viewed as a successor to previous work on asymptotic expansions for the radiation field. The key new elements are propagation estimates near the singularity of the potential, building on work of the first author with Wunsch and an explicit calculation with hypergeometric functions to determine the rates of decay., Comment: 50 pages, 2 figures. Version 3: minor changes to improve exposition and fix small errors, added discussion of higher-dimensional problem

Published
2021

18. Community-Dwelling Older Adults and Physical Activity Recommendations: Patterns of Aerobic, Strengthening, and Balance Activities.

Author

Wingood, Mariana, Bonnell, Levi, LaCroix, Andrea, Rosenberg, Dori, Walker, Rod, Bellettiere, John, Greenwood-Hickman, Mikael, Gell, Nancy, and Wing, David

Subjects
active aging, exercise, guidelines, health promotion, Aged, Exercise, Health Promotion, Humans, Independent Living, Longitudinal Studies, Surveys and Questionnaires
Abstract

Though it is known that most older adults do not meet the recommended physical activity (PA) guidelines, little is known regarding their participation in balance activities or the full guidelines. Therefore, we sought to describe PA patterns among 1,352 community-dwelling older adult participants of the Adult Changes in Thought study, a longitudinal cohort study exploring dementia-related risk factors. We used a modified version of the Community Healthy Activities Model Program for Seniors questionnaire to explore PA performed and classify participants as meeting or not meeting the full guidelines or any component of the guidelines. Logistic regression was used to identify factors associated with meeting PA guidelines. Despite performing 10 hr of weekly PA, only 11% of participants met the full guidelines. Older age, greater body mass index, needing assistance with instrumental daily activities, and heart disease were associated with decreased odds of meeting PA guidelines. These results can guide interventions that address PA among older adults.

Published
2022

19. Decoherent Histories Quantum Mechanics and Copenhagen Quantum Mechanics

Author

Gell-Mann, Murray and Hartle, James B

Subjects
Quantum Physics, General Relativity and Quantum Cosmology, Physics - History and Philosophy of Physics
Abstract

This paper discusses the relation between the decoherent histories approach to quantum mechanics that is based on coarse-grained decoherent histories of a closed system, and the approximate quantum mechanics of measured subsystems, as in the Copenhagen interpretation. We show how the a classical world used in such formulations is not to something to be postulated but rather explained by suitable sets of alternative histories of quasiclassical variables. We discuss the general definition of measurement, the collapse of the wave function, and irreversibility from the perspective of decoherent histories quantum theory.., Comment: 4 pages. arXiv admin note: substantial text overlap with arXiv:quant-ph/0609190, arXiv:2012.05229

Published
2021

21. 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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25. A Measure of Classicality

Author

Hartle, James B. and Gell-Mann, Murray

Subjects
General Relativity and Quantum Cosmology, Astrophysics - Cosmology and Nongalactic Astrophysics, High Energy Physics - Theory
Abstract

A striking feature of our fundamentally indeterministic quantum universe is its quasiclassical realm -- the wide range of time place and scale in which the deterministic laws of classical physics hold. Our quasiclassical realmis an emergent feature of the fundamental theories of our universe's quantum state and dynamics. There are many types of quasiclassical realms our Universe could exhibit characterized by different variables, different levels of coarse-graining, different locations in spacetime, different classical physics, and different levels of classicality.We propose a measure of classicality for quasiclassical realms, We speculate on the observable consequences of different levels of classicality especially for information gathering and utilizing systems (IGUSes) such ourselves as observers of the Universe., Comment: 9 pages, revtex4. arXiv admin note: substantial text overlap with arXiv:gr-qc/9509054

Published
2021

26. Regularity of the Scattering Matrix for Nonlinear Helmholtz Eigenfunctions

Author

Gell-Redman, Jesse, Hassell, Andrew, and Shapiro, Jacob

Subjects
Mathematics - Analysis of PDEs, 35P30, 35P25, 81Uxx
Abstract

We study the nonlinear Helmholtz equation $(\Delta - \lambda^2)u = \pm |u|^{p-1}u$ on $\mathbb{R}^n$, $\lambda > 0$, $p \in \mathbb{N}$ odd, and more generally $(\Delta_g + V - \lambda^2)u = N[u]$, where $\Delta_g$ is the (positive) Laplace-Beltrami operator on an asymptotically Euclidean or conic manifold, $V$ is a short range potential, and $N[u]$ is a more general polynomial nonlinearity. Under the conditions $(p-1)(n-1) > 4$ and $k > (n-1)/2$, for every $f \in H^k(S^{n-1}_\omega)$ of sufficiently small norm, we show there is a nonlinear Helmholtz eigenfunction taking the form \begin{equation*} u(r, \omega) = r^{-(n-1)/2} \Big( e^{-i\lambda r} f(\omega) + e^{+i\lambda r} b(\omega) + O(r^{-\epsilon}) \Big), \qquad \text{as } r \to \infty, \end{equation*} for some $b \in H^k(S_\omega^{n-1})$ and $\epsilon > 0$. That is, the scattering matrix $f \mapsto b$ preserves Sobolev regularity, which is an improvement over the authors' previous work with Zhang, that proved a similar result with a loss of four derivatives., Comment: 24 pages, 1 figure

Published
2020

27. Deep Learning is Singular, and That's Good

Author

Murfet, Daniel, Wei, Susan, Gong, Mingming, Li, Hui, Gell-Redman, Jesse, and Quella, Thomas

Subjects
Computer Science - Machine Learning
Abstract

In singular models, the optimal set of parameters forms an analytic set with singularities and classical statistical inference cannot be applied to such models. This is significant for deep learning as neural networks are singular and thus "dividing" by the determinant of the Hessian or employing the Laplace approximation are not appropriate. Despite its potential for addressing fundamental issues in deep learning, singular learning theory appears to have made little inroads into the developing canon of deep learning theory. Via a mix of theory and experiment, we present an invitation to singular learning theory as a vehicle for understanding deep learning and suggest important future work to make singular learning theory directly applicable to how deep learning is performed in practice.

Published
2020
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28. Divergent roles for KLF4 and TFCP2L1 in naive ground state pluripotency and human primordial germ cell development

Author

Hancock, GV, Liu, W, Peretz, L, Chen, D, Gell, JJ, Collier, AJ, Zamudio, Plath, K, and Clark, AT

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Stem Cell Research, Stem Cell Research - Embryonic - Human, Genetics, 1.1 Normal biological development and functioning, Underpinning research, Generic health relevance, Cell Differentiation, Germ Cells, Human Embryonic Stem Cells, Humans, Kruppel-Like Factor 4, Repressor Proteins, Transcription Factors, Transcriptome, Primordial Germ Cells, PGCs, hPGCs, Pluripotency, KLF4, Stem cells, TFCP2L1, Medical and Health Sciences, Developmental Biology, Medical biotechnology, Oncology and carcinogenesis
Abstract

During embryo development, human primordial germ cells (hPGCs) express a naive gene expression program with similarities to pre-implantation naive epiblast (EPI) cells and naive human embryonic stem cells (hESCs). Previous studies have shown that TFAP2C is required for establishing naive gene expression in these cell types, however the role of additional naive transcription factors in hPGC biology is not known. Here, we show that unlike TFAP2C, the naive transcription factors KLF4 and TFCP2L1 are not required for induction of hPGC-like cells (hPGCLCs) from hESCs, and they have no role in establishing and maintaining a naive-like gene expression program in hPGCLCs with extended time in culture. Taken together, our results suggest a model whereby the molecular mechanisms that drive naive gene expression in hPGCs/hPGCLCs are distinct from those in the naive EPI/hESCs.

Published
2021

29. Riemann moduli spaces are quantum ergodic

Author

Baskin, Dean, Gell-Redman, Jesse, and Han, Xiaolong

Subjects
Mathematics - Analysis of PDEs, Mathematics - Differential Geometry, Mathematics - Spectral Theory
Abstract

In this note we show that the Riemann moduli spaces $M_{g, n}$ equipped with the Weil--Petersson metric are quantum ergodic for $3g+n \geq 4$. We also provide other examples of singular spaces with ergodic geodesic flow for which quantum ergodicity holds., Comment: 15 pages; version 2: minor revisions suggested by referees

Published
2019

30. Existence and asymptotics of nonlinear Helmholtz eigenfunctions

Author

Gell-Redman, Jesse, Hassell, Andrew, Shapiro, Jacob, and Zhang, Junyong

Subjects
Mathematics - Analysis of PDEs, 35P30
Abstract

We prove the existence and asymptotic expansion of a large class of solutions to nonlinear Helmholtz equations of the form \begin{equation*} (\Delta - \lambda^2) u = N[u], \end{equation*} where $\Delta = -\sum_j \partial^2_j$ is the Laplacian on $\mathbb{R}^n$ with sign convention that it is positive as an operator, $\lambda$ is a positive real number, and $N[u]$ is a nonlinear operator that is a sum of monomials of degree $\geq p$ in $u$, $\overline{u}$ and their derivatives of order up to two, for some $p \geq 2$. Nonlinear Helmholtz eigenfunctions with $N[u]= \pm |u|^{p-1} u$ were first considered by Guti\'errez. Such equations are of interest in part because, for certain nonlinearities $N[u]$, they furnish standing waves for nonlinear evolution equations, that is, solutions that are time-harmonic. We show that, under the condition $(p-1)(n-1)/2 > 2$ and $k > (n-1)/2$, for every $f \in H^{k+2}(\mathbb{S}^{n-1})$ of sufficiently small norm, there is a nonlinear Helmholtz function taking the form \begin{equation*} u(r, \omega) = r^{-(n-1)/2} \Big( e^{-i\lambda r} f(\omega) + e^{+i\lambda r} g(\omega) + O(r^{-\epsilon}) \Big), \text{ as } r \to \infty, \quad \epsilon > 0, \end{equation*} for some $g \in H^{k}(\mathbb{S}^{n-1})$. Moreover, we prove the result in the general setting of asymptotically conic manifolds., Comment: 36 pages, 2 figures

Published
2019

31. Alternative Decohering Histories in Quantum Mechanics

Author

Gell-Mann, Murray and Hartle, James

Subjects
Quantum Physics, General Relativity and Quantum Cosmology, High Energy Physics - Theory, Physics - History and Philosophy of Physics
Abstract

We continue our efforts to understand, within the framework of the quantum mechanics of the universe as a whole, the quasiclassical realm of familiar experience as a feature emergent from the Hamiltonian of the elementary particles and the initial condition of the universe. Quantum mechanics assigns probabilities to exhaustive sets of alternative decoherent histories of the universe. We introduce and define the notion of strong decoherence. We replace the notion of maximal sets of alternative decohering histories by defining the more useful concept of "full" sets of alternative strongly decohering histories. These full sets fall into equivalence classes each of which is characterized by a basis in Hilbert space. Finally we describe our continuing efforts to find measures of classicality --- measures that could be applied to such full sets of alternative strongly decohering so as to characterize a quasiclassical realm., Comment: a pre-arXiv paper posted for greater accessibility, revtex4, 17pages

Published
2019

32. An Extended Culture System that Supports Human Primordial Germ Cell-like Cell Survival and Initiation of DNA Methylation Erasure

Author

Gell, Joanna J, Liu, Wanlu, Sosa, Enrique, Chialastri, Alex, Hancock, Grace, Tao, Yu, Wamaitha, Sissy E, Bower, Grace, Dey, Siddharth S, and Clark, Amander T

Subjects
Biological Sciences, Genetics, Stem Cell Research, Human Genome, Stem Cell Research - Induced Pluripotent Stem Cell, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Stem Cell Research - Embryonic - Human, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Generic health relevance, Cell Culture Techniques, Cell Proliferation, Cell Self Renewal, Cell Survival, Cells, Cultured, Chromatin Assembly and Disassembly, DNA Demethylation, DNA Methylation, Germ Cells, Histones, Humans, Transcription, Genetic, Transcriptome, human, primordial germ cell-like cells, primordial germ cells, Biochemistry and Cell Biology, Clinical Sciences, Biochemistry and cell biology
Abstract

The development of an in vitro system in which human primordial germ cell-like cells (hPGCLCs) are generated from human pluripotent stem cells (hPSCs) has been invaluable to further our understanding of human primordial germ cell (hPGC) specification. However, the means to evaluate the next fundamental steps in germ cell development have not been well established. In this study we describe a two dimensional extended culture system that promotes proliferation of specified hPGCLCs, without reversion to a pluripotent state. We demonstrate that hPGCLCs in extended culture undergo partial epigenetic reprogramming, mirroring events described in hPGCs in vivo, including a genome-wide reduction in DNA methylation and maintenance of depleted H3K9me2. This extended culture system provides a new approach for expanding the number of hPGCLCs for downstream technologies, including transplantation, molecular screening, or possibly the differentiation of hPGCLCs into gametes by in vitro gametogenesis.

Published
2020

34. JET machine operations in T&D-T

Author

The JET Operations Team (presented by D.B. King), E. Abdelrahman, A. Abdul Hamid, N. Abid, K. Abraham, O. Adabonyan, C. Adlam, M. Afzal, M. Akhtar, V. Aldred, S. Aldworth, S. Aleiferis, M. Ali, R. Alie, R. Allan, H. Allen, E. Alli, M. Allinson, P. Almond, J. Angus, K. Antcliffe, I. Antoniou, L. Appel, C. Appelbee, C. Aramunde, N. Archer, S. Aria, H. Arkuszynski, M. Arshad, G. Artaserse, A. Ash, C. Ashe, T. Aue, D. Auld, B. Austin, Y. Austin, C. Ayres, R.B. Morales, S. Baker, S. Bakes, I. Balboa, C. Balshaw, N. Balshaw, J. Banks, J. Banner, A. Barnard, M. Barnard, M. Baruzzo, C. Basagiannis, S. Bathe Hariyanandan, P. Batistoni, R. Baughan, P. Beaumont, D. Beckett, A. Begolli, M. Beldishevski, K. Bell, E. Belonohy, J. Bentley, J. Bernardo, M. Berry, J. Bhatt, S. Bickerton, J. Bielecki, W. Bird, D. Blackett, K. Blackman, S. Blake, P. Blatchford, A. Bleasdale, A. Boboc, J. Booth, P. Boulting, M. Bowden, C. Boyd, K. Boyd, R. Bracey, D. Brennan, A. Brett, M. Bright, M. Brix, I. Brooks, B. Brown, P. Brown, M. Brown, P. Brummitt, B. Viola, A. Buckingham, M. Buckley, J. Bumpass, M. Burford, A. Burgess, J. Burton-Sweeten, A. Busse, D. Butcher, P. Cahill, P. Camp, I. Campbell, R. Canavan, J. Cane, M. Cannon, N. Canterbury, A. Carberry, P. Card, M. Carlick, M. Carlo, P. Carman, A. Carruthers, S. Carter, I.S. Carvalho, P. Carvalho, F. Casson, D. Chalk, B. Chamberlain, P. Chauhan, A. Chow, A. Churchman, D. Ciric, M. Clark, J. Clarkson, R. Clarkson, T. Clayton, M. Cleverly, P. Coates, I. Coffey, J. Collins, S. Conroy, N.J. Conway, R. Conway, J. Cook, M. Cooke, D. Coombs, P. Cooper, S. Cooper, G. Corrigan, R. Cotterell, A. Coulson, M. Cox, S. Cox, S. Cramp, D. Craven, R. Craven, M. Crick, D. Croft, T. Cronin, Z. Cui, A. Cullen, R. Cumming, C. Cummings, A. Dal Molin, P. Dalgliesh, S. Dalley, A. Danquah, S. Davies, G. Davis, H. Dawson, K. Dawson, S. Dawson, I. Day, L. de Caires, E. de la Luna, K. Deakin, J. Deane, M. Dearing, A. Dennett, T. Dickson, J. Dobrashian, T. Dochnal, S. Dorling, D. Douai, S. Dowson, J. Drewitt, G. Drummond, P. Dumortier, R. Eade, R. Eastham, K. Eden, J. Edmond, J. Edwards, P. Edwards, H. Elamin, S. Elford, H. El-Haroun, P. Ellis, C. Elsmore, S. Emery, G. Evans, S. Evans, D. Fagan, T. Farmer, I. Farquhar, R. Felton, F. Ferner, J. Fessey, P. Finburg, G. Fishpool, L. Fittill, J. Flanagan, K. Flinders, S. Foley, M. Fontana, M. Fortune, J. Foster, C. Fowler, P. Fox, O. Franklin, R. Franklin, R. Fraser, S. French, M. Furseman, A. Gabbidon, L. Garcia, J. Garcia, M. Gardener, D. Gear, T. Gedling, S. Gee, P. Gell, R. George, S. Gerasimov, M. Gethins, Z. Ghani, L. Giacomelli, C. Gibson, V. Gilsenan, C. Giroud, R. Glen, J. Goff, C. Goodman, A. Goodyear, A. Gordon, S. Gore, S. Gosden, N. Gotts, E. Gow, W. Graham, G. Graham, M. Green, R. Gregory, R. Griffiths, T. Griffiths, F. Griph, C. Grundy, T. Grundy, D. Guard, D. Guest, C. Gurl, S. Hacquin, A. Hakola, K. Hammond, H. Harmer, P. Harper, S. Harris, D. Hart, D. Hattan, A. Haupt, J. Hawes, N. Hawkes, J. Hawkins, P. Hawkins, S. Hayes, S. Hazael, D. Heads, P. Heesterman, O. Hemming, R.B. Henriques, G. Hermon, G. Hewson, T. Hibberd, M. Hill, J. Hillesheim, I. Hirb, K. Ho, C. Hogben, A. Hollingsworth, S. Hollis, M. Hook, D. Hopley, N. Horsten, A. Horton, L.D. Horton, L. Horvath, S. Hotchin, Z. Huang, E. Hubenov, V. Huber, A. Huber, C. Huddart, T. Huddleston, T. Hunter, Y. Husain, A. Hynes, J. Ingleby, S. Ives, E. Ivings, S. Jackson, T. Jackson, P. Jacquet, N. Jayasekera, I. Jepu, D. Jezzard, E. Joffrin, R. Johnson, J. Johnston, C. Jones, E. Jones, G. Jones, L. Jones, S. Jones, T. Jones, M. Jones, A. Joyce, M. Juvonen, A. Kantor, A. Kappatou, G. Karajgikar, J. Karhunen, I. Karnowska-Paterski, E. Karsakos, G. Kaveney, G. Kay, D. Keeling, T. Keenan, R. Kelly, W. Kelly, D. Kennedy, R. Kennedy, O. Kent, K. Khan, D. King, D. Kinna, V. Kiptily, K. Kirov, G. Kneale, M. Knight, P. Knight, J. Knipe, R. Knipe, S. Knipe, P. Kochanski, D. Kos, M. Kovari, E. Kowalska-Strzęciwilk, N. Kraus, M. Kresina, B. Labit, A. Laing, V. Laksharam, N. Lam, B. Lane, C. Lane, T. Lavender, A. Lawson, K. Lawson, G. Learoyd, T. Leeson, X. Lefebvre, J. Lehmann, M. Lennholm, K. Lennon, E. Lerche, S. Lesnoj, E. Letellier, L. Lewin, J. Lewis, J. Li, G. Liddiard, E. Litherland-Smith, F. Liu, R. Lobel, J. Logan, P. Lomas, C. Long, U. Losada, C. Loveridge, T. Lowe, C. Lowry, R. Lucock, G. Lyons, J. Macdonald, P. Macheta, T. Madden, J. Maddock, C.F. Maggi, J. Mailloux, A. Manning, C. Manning, N. Mantel, A. Manzanares, S. Marsden, J. Marsh, R. Marshall, A. Martin, M. Maslov, G. Matthews, N. Mayfield, M. Mayoral, R. McAdams, L. McCafferty, P. McCullen, D. McDonald, A. McDonnell, D. McGuckin, T. McIver, V. McKay, R. McKean, L. McNamee, A. McShee, R. Meadows, D. Mederick, M. Medland, K. Meghani, A. Meigs, S. Menmuir, I. Merrigan, S. Mianowski, P. Middleton, C. Miles, J. Milnes, A. Milocco, J. Mitchell, P. Mitchell, P. Monaghan, I. Monakhov, P. Moody, R. Mooney, C. Moore, N. Mooring, L. Morgan, R. Morgan, J. Morris, O. Morton, S. Morton, P. Mulvana, S. Munot, R. Munro-Smith, K. Musgrave, R. Naish, N. Neethiraj, J. Neilson, A. Newman, S. Ng, M. Nicassio, K. Nicholls, M. Nightingale, C. Noble, R. Normington, C. Nygaard, J. O’Callaghan, R. Olney, B. O’Meara, M. O’Mullane, C. O’Neill, C. Opara, K. O’Rourke, J. Ottley, K. Otu, A. Owen, N. Pace, K. Palamartchouk, D. Paley, J. Palgrave, G. Papadopoulos, V. Parail, A. Parrott, A. Parsloe, L. Parsons, R. Parsons, A. Patel, J. Patel, A. Peacock, M. Pearce, T. Pearce, I. Pearson, J. Penzo, A. Perdas, T. Pereira, C. Perez Von Thun, D. Perry, N. Petrella, M. Peyman, N. Platt, M. Poradzinski, M. Porter, M. Porton, C. Powell, J. Pozzi, M. Price, L. Price, P. Puglia, D. Pulley, K. Purahoo, M. Rainford, A. Raj, S. Randhawa, S. Rapa, K. Ravisankar, C. Rayner, A. Read, C. Reux, S. Reynolds, V. Riccardo, L. Richiusa, D. Rigamonti, F. Rimini, J. Roberts, R. Robins, S. Robinson, T. Robinson, D. Robson, S. Romanelli, F. Rose, C. Rose-Innes, D. Rouse, S. Rowe, N. Rowland, D. Rowlands, M. Rubel, K. Sabin, R. Salmon, H. Salter, A. Sanders, E. Sanders, I. Sanders, D. Sandiford, F. Sanni, R. Sarwar, R. Sayles, C. Scaysbrook, G. Scott, D. Scraggs, S. Scully, R. Sealey, E. Searle, M. Segato, M. Sertoli, C. Shanks, R. Sharma, A. Shaw, K. Sheahan, H. Sheikh, D. Shrestha, R. Siddiqui, S. Silburn, J. Silva, D. Simfukwe, J. Simpson, M. Sinclair, A. Sips, P. Sirén, S. Skeats, N. Skinner, B. Slade, J. Slater, T. Smart, G. Smith, J. Smith, N. Smith, P. Smith, T. Smith, F. P. Smith, J. Snell, K. Snelling, K. Soare, E. Solano, A. Spelzini, C. Srinivasan, Z. Stancar, P.A. Staniec, M. Stead, R. Steadman, L. Steel, D. Steele, A. Stephen, J. Stephens, L. Stevenson, P. Stevenson, C. Steventon, L. Sticklen, M. Stojanov, S. Strikwerda, C. Stuart, G. Stubbs, N. Studd, W. Studholme, H. Sun, S. Surendran, G. Szepesi, M. Szoke, H. Tan, A. Taylor, D. Taylor, K. Taylor, A. Thingore, B. Thomas, J. Thomas, A. Thorman, A. Tilley, A. Tipton, N. Tipton, H. Todd, P. Tonner, A. Tookey, M. Towndrow, M. Tsang, E. Tsitrone, I. Turner, M. Turner, G. Tvalashvili, S. Tyrrell, A. Vadgama, D. Valcarcel, Q. Van Der Westhuizen, J. Verdon, N. Vianello, A. Vittal, Z. Vizvary, B. Wakeling, M. Walker, R. Walker, T. Wall, M. Walsh, T. Walsh, J. Walters, J. Walton, R. Walton, S. Warder, F. Warren, R. Warren, J. Waterhouse, T. Webster, G. Wells, C. Wellstood, A. West, M. Wheatley, S. Whiffin, A. Whitehead, C. Whitehead, D. Whittaker, A. Widdowson, J. Wilcox, D. Wilkins, R. Wilkins, J. Williams, M. Williams, D. Willoughby, A. Wilson, I. Wilson, T. Wilson, M. Wischmeier, P. Wise, G. Withenshaw, A. Withycombe, D. Witts, J. Witts, R. Wood, L. Woodham, C. Woodley, J. Woodley, R. Woodley, B. Woods, S. Wray, T. Xu, I. Young, R. Young, K-D. Zastrow, Y. Zayachuk, and M. Zerbini

Subjects
JET, tritium, operations, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Abstract

JET, the world’s largest operating tokamak with unique Be/W wall and tritium handling capability, completed a Deuterium-Tritium (D-T) campaign in 2021 (Maggi et al 29th Fusion Energy Conf. ) following a decade of preparatory experiments, dedicated enhancements, technical rehearsals and training (Horton et al 2016 Fusion Eng. Des. 109–111 925). Operation with tritium raises significant technical, safety and scientific challenges not encountered in standard protium or deuterium operation. This contribution describes the tritium operational requirements, pulses and technical preparations, new operating procedures, lessons learned and details on the achieved operational availability and performance. The preparation and execution of the recent JET tritium experiments benefitted from the previous experience in 1991 (Preliminary Tritium Experiment), 1997 (DTE1 campaign) and 2003 (Trace Tritium Campaigns) and consisted of the following five phases: technical rehearsals and scenario preparation, tritium commissioning, 100% tritium campaign, D-T campaign (DTE2), tritium clean-up. Following the clean-up JET resumed normal operation and is currently undertaking a further D-T campaign (DTE3).

Published
2024
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35. Quantum Mechanics in the Light of Quantum Cosmology

Author

Gell-Mann, Murray and Hartle, James B.

Subjects
General Relativity and Quantum Cosmology, Quantum Physics
Abstract

We sketch a quantum mechanical framework for the universe as a whole. Within that framework we propose a program for describing the ultimate origin in quantum cosmology of the quasiclassical domain of familiar experience and for characterizing the process of measurement. Predictions in quantum mechanics are made from probabilities for sets of alternative histories. Probabilities can be assigned only to sets of histories that approximately decohere. Decoherence is defined and the mechanism of decoherence is reviewed. Decoherence requires a sufficiently coarse-grained description of alternative histories of the universe. A quasiclassical domain consists of a branching set of alternative decohering histories, described by a coarse graining that is maximally refined consistent with decoherence, with individual branches that exhibit a high level of classical correlation in time. A quasiclassical domain is emergent in the universe as a consequence of the initial condition and the action function of the elementary particles. It is an important question whether all the quasiclassical domains are roughly equivalent or whether there are various essentially inequivalent ones. A measurement is a correlation with variables in a quasiclassical domain. An observer (or information gathering and utilizing system) is a complex adaptive system that has evolved to exploit the relative predictability of a quasiclassical domain. We suggest that resolution of many of the problems of interpretation presented by quantum mechanics is to be accomplished, not by further scrutiny of the subject as it applies to reproducible laboratory situations, but rather by an examination of alternative histories of the universe, stemming from its initial condition, and a study of the problem of quasiclassical domains., Comment: 29 pages, 4 figures, pdf, an older paper posted for accessibility

Published
2018

36. The index formula for families of Dirac type operators on pseudomanifolds

Author

Albin, Pierre and Gell-Redman, Jesse

Subjects
Mathematics - Differential Geometry, Mathematics - Analysis of PDEs, Mathematics - Geometric Topology, 58J20 32S60
Abstract

We study families of Dirac-type operators, with compatible perturbations, associated to wedge metrics on stratified spaces. We define a closed domain and, under an assumption of invertible boundary families, prove that the operators are self-adjoint and Fredholm with compact resolvents and trace-class heat kernels. We establish a formula for the Chern character of their index.

Published
2017

37. Remotely Delivered Exercise to Rural Older Adults With Knee Osteoarthritis: A Pilot Study

Author

Kushang V. Patel, Elise V. Hoffman, Elizabeth A. Phelan, and Nancy M. Gell

Subjects
Diseases of the musculoskeletal system, RC925-935
Abstract

Objective EnhanceFitness (EF) is an evidence‐based exercise program recommended for management of osteoarthritis (OA). However, access to EF is limited in rural areas. Accordingly, we evaluated the feasibility and acceptability of remotely delivered EF (tele‐EF) in rural, community‐dwelling older adults with symptomatic knee OA. Methods A single‐arm pilot trial of tele‐EF classes was conducted. Videoconferencing was used to livestream the instructor‐led, 1‐hour EF classes 3 days/week for 12 weeks. Outcomes were assessed at baseline and immediately post intervention. Results A total of 15 of 27 potential participants (55%) were screen eligible and enrolled into the trial. Participants had a median age of 70 years (interquartile range: 67‐75), and 14 (93%) were women. The median EF class attendance rate was 91% (interquartile range: 85%‐94%). Knee pain, as measured by the Knee Injury and Osteoarthritis Outcome Score (KOOS), improved significantly from baseline to the 12‐week end point (mean difference = −11.4 [95% confidence interval (CI): −20.9 to −2.0]; P = 0.02). In addition, participants’ self‐reported knee function improved significantly (mean difference in KOOS function score = −11.8 [95% CI: −18.4 to −5.2]; P

Published
2022
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38. The TFAP2C-Regulated OCT4 Naive Enhancer Is Involved in Human Germline Formation.

Author

Chen, Di, Liu, Wanlu, Zimmerman, Jill, Pastor, William A, Kim, Rachel, Hosohama, Linzi, Ho, Jamie, Aslanyan, Marianna, Gell, Joanna J, Jacobsen, Steven E, and Clark, Amander T

Subjects
Germ Cells, Chromatin, Pluripotent Stem Cells, Humans, Gene Expression Regulation, Developmental, Female, Male, Transcription Factor AP-2, Octamer Transcription Factor-3, Kruppel-Like Transcription Factors, Enhancer Elements, Genetic, Transcriptome, Nucleotide Motifs, OCT4, PGC, PGCLC, TFAP2C, enhancer, naive, pluripotency, Gene Expression Regulation, Developmental, Enhancer Elements, Genetic, Biochemistry and Cell Biology, Medical Physiology
Abstract

Human primordial germ cells (hPGCs) are the first embryonic progenitors in the germ cell lineage, yet the molecular mechanisms required for hPGC formation are not well characterized. To identify regulatory regions in hPGC development, we used the assay for transposase-accessible chromatin using sequencing (ATAC-seq) to systematically characterize regions of open chromatin in hPGCs and hPGC-like cells (hPGCLCs) differentiated from human embryonic stem cells (hESCs). We discovered regions of open chromatin unique to hPGCs and hPGCLCs that significantly overlap with TFAP2C-bound enhancers identified in the naive ground state of pluripotency. Using CRISPR/Cas9, we show that deleting the TFAP2C-bound naive enhancer at the OCT4 locus (also called POU5F1) results in impaired OCT4 expression and a negative effect on hPGCLC identity.

Published
2018

39. Evidencia de pobre diversidad genética del manjuarí (Atractosteus tristoechus)

Author

Gabriela Ulmo-Díaz, Jessy Castellanos-Gell, José Luis Ponce de León, Didier Casane, Andrés Hurtado, and Erik García-Machado

Subjects
Especie en peligro, genética de la conservación, lepisosteidos, manejo genético en cautividad, Geography. Anthropology. Recreation, Oceanography, GC1-1581
Abstract

El manjuarí (Atractosteus tristoechus) es un pez de agua dulce endémico de Cuba. Entre los Lepisosteiformes, esta especie es una de las más amenazadas y ocupa la menor área de distribución natural. Está restringida al área suroeste del archipiélago cubano. Esta investigación se enfoca en la caracterización genética de las poblaciones cautivas y naturales de la Ciénaga de Zapata, mediante dos secuencias mitocondriales (gen que codifica citocromo c oxidasa I y la Región de Control) y nueve loci microsatélite. Un total de 47 individuos fueron incluidos en la investigación. Se detectó baja variabilidad genética: h = 0.202 ± 0.077 y π = 0.00021 ± 0.00008 para las secuencias mitocondriales; Ho=0.016 y He =0.025 para los microsatélites. Entre los lepisosteidos estudiados hasta el momento, esta especie muestra la menor variabilidad genética. Estos resultados sugieren que A. tristoechus ha mantenido un pequeño tamaño efectivo poblacional durante largo tiempo y/o la población ha experimentado un cuello de botella reciente. Dada la reciente tendencia demográfica de la especie, y la baja diversidad genética mostrada en este estudio, se hace necesaria con urgencia unaatención especial, así como esfuerzos para su conservación.

Published
2023

41. Citizen scientists track a charismatic carnivore: Mapping the spread and impact of the South African Mantis (Miomantidae, Miomantis caffra) in Australia

Author

Matthew G. Connors, Honglei Chen, Haokun Li, Adam Edmonds, Kimberley A. Smith, Colin Gell, Kelly Clitheroe, Ishbel Morag Miller, Kenneth L. Walker, Jack S. Nunn, Linh Nguyen, Luke N. Quinane, Chiara M. Andreoli, Jason A. Galea, Brendon Quan, Katrina Sandiford, Brendan Wallis, Matthew L. Anderson, Elizabeth Valeria Canziani, Jade Craven, Roi R. C. Hakim, Rod Lowther, Cindy Maneylaws, Bastian A. Menz, John Newman, Harvey D. Perkins, Alistair R. Smith, Vanessa H. Webber, and Dylan Wishart

Subjects
Zoology, QL1-991
Abstract

The recent integration of citizen science with modern technology has greatly increased its applications and has allowed more people than ever to contribute to research across all areas of science. In particular, citizen science has been instrumental in the detection and monitoring of novel introduced species across the globe. This study provides the first records of Miomantis caffra Saussure, 1871, the South African Mantis, from the Australian mainland and uses records from four different citizen science and social media platforms in conjunction with museum records to track the spread of the species through the country. A total of 153 wild mantises and oothecae were observed across four states and territories (New South Wales, Norfolk Island, Victoria, and Western Australia) between 2009 and 2021. The large number of observations of the species in Victoria and the more recent isolated observations in other states and territories suggest that the species initially arrived in Geelong via oothecae attached to plants or equipment, likely from the invasive population in New Zealand. From there it established and spread outwards to Melbourne and eventually to other states and territories, both naturally and with the aid of human transport. We also provide a comparison of M. caffra to similar native mantises, specifically Pseudomantis albofimbriata (Stål, 1860), and comment on the potential impact and further spread of the species within Australia. Finally, we reiterate the many benefits of engaging directly with citizen scientists in biodiversity research and comment on the decision to include them in all levels of this research investigation.

Published
2022
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42. Brain connectivity fingerprinting and behavioural prediction rest on distinct functional systems of the human connectome

Author

Maron Mantwill, Martin Gell, Stephan Krohn, and Carsten Finke

Subjects
Biology (General), QH301-705.5
Abstract

Mantwill et al. analysed the relationship between functional connectivity markers that are specific to individuals (i.e. brain fingerprints) and those predictive of behaviour. They reveal that these markers are unrelated and suggest an alternative perspective on the basis of individual signatures.

Published
2022
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43. Equidistribution of Phase Shifts in Obstacle Scattering

Author

Gell-Redman, Jesse and Ingremeau, Maxime

Subjects
Mathematics - Spectral Theory, Mathematical Physics, Mathematics - Analysis of PDEs
Abstract

For scattering off a smooth, strictly convex obstacle $\Omega \subset \mathbb{R}^d$ with positive curvature, we show that the eigenvalues of the scattering matrix -- the phase shifts -- equidistribute on the unit circle as the frequency $k \to \infty$ at a rate proportional to $k^{d - 1}$, under a standard condition on the set of closed orbits of the billiard map in the interior. Indeed, in any sector $S \subset \mathbb{S}^1$ not containing $1$, there are $c_d |S| \mathrm{Vol}(\partial \Omega)\ k^{d - 1} + o(k^{d-1})$ eigenvalues for $k$ large, where $c_d$ is a constant depending only on the dimension. Using this result, the two term asymptotic expansion for the counting function of Dirichlet eigenvalues, and a spectral-duality result of Eckmann-Pillet, we then give an alternative proof of the two term asymptotic of the total scattering phase due to Majda-Ralston., Comment: 14 pages, 2 figures. Final published version. Extensively revised

Published
2017
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45. Energetics underlying hemin extraction from human hemoglobin by Staphylococcus aureus

Author

Sjodt, Megan, Macdonald, Ramsay, Marshall, Joanna D, Clayton, Joseph, Olson, John S, Phillips, Martin, Gell, David A, Wereszczynski, Jeff, and Clubb, Robert T

Subjects
Infectious Diseases, Hematology, Antigens, Bacterial, Binding Sites, Biopolymers, Calorimetry, Cation Transport Proteins, Energy Metabolism, Hemin, Hemoglobins, Humans, Hydrolysis, Kinetics, Molecular Dynamics Simulation, Nuclear Magnetic Resonance, Biomolecular, Protein Binding, Protein Conformation, Receptors, Cell Surface, Staphylococcus aureus, Thermodynamics, bacterial pathogenesis, receptor, hemoglobin, isothermal titration calorimetry, molecular dynamics, iron-regulated surface determinant system, IsdB, IsdH, NEAT domain, stopped-flow spectrophotometry, Chemical Sciences, Biological Sciences, Medical and Health Sciences, Biochemistry & Molecular Biology
Abstract

Staphylococcus aureus is a leading cause of life-threatening infections in the United States. It actively acquires the essential nutrient iron from human hemoglobin (Hb) using the iron-regulated surface-determinant (Isd) system. This process is initiated when the closely related bacterial IsdB and IsdH receptors bind to Hb and extract its hemin through a conserved tri-domain unit that contains two NEAr iron Transporter (NEAT) domains that are connected by a helical linker domain. Previously, we demonstrated that the tri-domain unit within IsdH (IsdHN2N3) triggers hemin release by distorting Hb's F-helix. Here, we report that IsdHN2N3 promotes hemin release from both the α- and β-subunits. Using a receptor mutant that only binds to the α-subunit of Hb and a stopped-flow transfer assay, we determined the energetics and micro-rate constants of hemin extraction from tetrameric Hb. We found that at 37 °C, the receptor accelerates hemin release from Hb up to 13,400-fold, with an activation enthalpy of 19.5 ± 1.1 kcal/mol. We propose that hemin removal requires the rate-limiting hydrolytic cleavage of the axial HisF8 Nϵ-Fe3+ bond, which, based on molecular dynamics simulations, may be facilitated by receptor-induced bond hydration. Isothermal titration calorimetry experiments revealed that two distinct IsdHN2N3·Hb protein·protein interfaces promote hemin release. A high-affinity receptor·Hb(A-helix) interface contributed ∼95% of the total binding standard free energy, enabling much weaker receptor interactions with Hb's F-helix that distort its hemin pocket and cause unfavorable changes in the binding enthalpy. We present a model indicating that receptor-introduced structural distortions and increased solvation underlie the IsdH-mediated hemin extraction mechanism.

Published
2018

46. PRDM14 is expressed in germ cell tumors with constitutive overexpression altering human germline differentiation and proliferation

Author

Gell, Joanna J, Zhao, Jasmine, Chen, Di, Hunt, Timothy J, and Clark, Amander T

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Cancer, Stem Cell Research, Stem Cell Research - Embryonic - Human, Generic health relevance, Adolescent, Adult, Cell Differentiation, Cell Proliferation, Child, Child, Preschool, DNA-Binding Proteins, Female, Germ Cells, Humans, Infant, Male, Neoplasms, Germ Cell and Embryonal, Pluripotent Stem Cells, RNA-Binding Proteins, Repressor Proteins, Teratoma, Transcription Factors, Young Adult, Germ cell tumor, PRDM14, Cell differentiation, Primordial germ cell, Proliferation, Medical and Health Sciences, Developmental Biology, Genetics, Medical biotechnology, Oncology and carcinogenesis
Abstract

Germ cell tumors (GCTs) are a heterogeneous group of tumors occurring in gonadal and extragonadal locations. GCTs are hypothesized to arise from primordial germ cells (PGCs), which fail to differentiate. One recently identified susceptibility loci for human GCT is PR (PRDI-BF1 and RIZ) domain proteins 14 (PRDM14). PRDM14 is expressed in early primate PGCs and is repressed as PGCs differentiate. To examine PRDM14 in human GCTs we profiled human GCT cell lines and patient samples and discovered that PRDM14 is expressed in embryonal carcinoma cell lines, embryonal carcinomas, seminomas, intracranial germinomas and yolk sac tumors, but is not expressed in teratomas. To model constitutive overexpression in human PGCs, we generated PGC-like cells (PGCLCs) from human pluripotent stem cells (PSCs) and discovered that elevated expression of PRDM14 does not block early PGC formation. Instead, we show that elevated PRDM14 in PGCLCs causes proliferation and differentiation defects in the germline.

Published
2018

47. Carbohydrates from Pseudomonas aeruginosa biofilms interact with immune C-type lectins and interfere with their receptor function

Author

Sonali Singh, Yasir Almuhanna, Mohammad Y. Alshahrani, Douglas W. Lowman, Peter J. Rice, Chris Gell, Zuchao Ma, Bridget Graves, Darryl Jackson, Kelly Lee, Rucha Juarez, Janice Koranteng, Sirina Muntaka, Daniel A. Mitchell, Ana C. da Silva, Farah Hussain, Gokhan Yilmaz, Francesca Mastrotto, Yasuhiko Irie, Paul Williams, David L. Williams, Miguel Cámara, and Luisa Martinez-Pomares

Subjects
Microbial ecology, QR100-130
Abstract

Abstract Bacterial biofilms represent a challenge to the healthcare system because of their resilience against antimicrobials and immune attack. Biofilms consist of bacterial aggregates embedded in an extracellular polymeric substance (EPS) composed of polysaccharides, nucleic acids and proteins. We hypothesised that carbohydrates could contribute to immune recognition of Pseudomonas aeruginosa biofilms by engaging C-type lectins. Here we show binding of Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN, CD209), mannose receptor (MR, CD206) and Dectin-2 to P. aeruginosa biofilms. We also demonstrate that DC-SIGN, unlike MR and Dectin-2, recognises planktonic P. aeruginosa cultures and this interaction depends on the presence of the common polysaccharide antigen. Within biofilms DC-SIGN, Dectin-2 and MR ligands appear as discrete clusters with dispersed DC-SIGN ligands also found among bacterial aggregates. DC-SIGN, MR and Dectin-2 bind to carbohydrates purified from P. aeruginosa biofilms, particularly the high molecular weight fraction (HMW; >132,000 Da), with KDs in the nM range. These HMW carbohydrates contain 74.9–80.9% mannose, display α-mannan segments, interfere with the endocytic activity of cell-associated DC-SIGN and MR and inhibit Dectin-2-mediated cellular activation. In addition, biofilm carbohydrates reduce the association of the DC-SIGN ligand Lewisx, but not fucose, to human monocyte-derived dendritic cells (moDCs), and alter moDC morphology without affecting early cytokine production in response to lipopolysaccharide or P. aeruginosa cultures. This work identifies the presence of ligands for three important C-type lectins within P. aeruginosa biofilm structures and purified biofilm carbohydrates and highlights the potential for these receptors to impact immunity to P. aeruginosa infection.

Published
2021
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48. Modeling human infertility with pluripotent stem cells

Author

Chen, Di, Gell, Joanna J, Tao, Yu, Sosa, Enrique, and Clark, Amander T

Subjects
Medical Biotechnology, Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Regenerative Medicine, Genetics, Stem Cell Research - Embryonic - Non-Human, Stem Cell Research, Stem Cell Research - Embryonic - Human, Contraception/Reproduction, Stem Cell Research - Induced Pluripotent Stem Cell, Infertility, Stem Cell Research - Nonembryonic - Non-Human, Underpinning research, 1.1 Normal biological development and functioning, Reproductive health and childbirth, Generic health relevance, Cell Lineage, Germ Cells, Humans, Models, Biological, Pluripotent Stem Cells, Reproduction, Medical and Health Sciences, Developmental Biology, Medical biotechnology, Oncology and carcinogenesis
Abstract

Human fertility is dependent upon the correct establishment and differentiation of the germline. This is because no other cell type in the body is capable of passing a genome and epigenome from parent to child. Terminally differentiated germline cells in the adult testis and ovary are called gametes. However, the initial specification of germline cells occurs in the embryo around the time of gastrulation. Most of our knowledge regarding the cell and molecular events that govern human germline specification involves extrapolating scientific principles from model organisms, most notably the mouse. However, recent work using next generation sequencing, gene editing and differentiation of germline cells from pluripotent stem cells has revealed that the core molecular mechanisms that regulate human germline development are different from rodents. Here, we will discuss the major molecular pathways required for human germline differentiation and how pluripotent stem cells have revolutionized our ability to study the earliest steps in human embryonic lineage specification in order to understand human fertility.

Published
2017

49. Novel association of familial testicular germ cell tumor and autosomal dominant polycystic kidney disease with PKD1 mutation

Author

Truscott, Laurel, Gell, Joanna, Chang, Vivian Y, Lee, Hane, Strom, Samuel P, Pillai, Rex, Sisk, Anthony, Martinez‐Agosto, Julian A, Anderson, Martin, and Federman, Noah

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Urologic Diseases, Cancer, Polycystic Kidney Disease, Genetics, Kidney Disease, Pediatric, Aetiology, 2.1 Biological and endogenous factors, Renal and urogenital, Adolescent, Antineoplastic Combined Chemotherapy Protocols, Female, Humans, Male, Mutation, Neoplasms, Germ Cell and Embryonal, Pedigree, Phenotype, Polycystic Kidney, Autosomal Dominant, Prognosis, TRPP Cation Channels, Testicular Neoplasms, PKD1, exome sequencing, familial testicular germ cell tumor, Clinical Sciences, Oncology and Carcinogenesis, Paediatrics and Reproductive Medicine, Oncology & Carcinogenesis, Oncology and carcinogenesis, Paediatrics
Abstract

Adolescent brothers were diagnosed with testicular germ cell tumors within the same month. Both were found to have multiple renal cysts on pretreatment imaging done for staging. The proband, his brother, and their mother, were all found to have a novel splice variant in intron 8 of the PKD1 gene by clinical exome sequencing. This is the second family reported with both familial testicular germ cell tumor (FTGCT) and autosomal dominant polycystic kidney disease (ADPKD), and the first described association of FTGCT with a splice variant in PKD1. We suggest that this novel variant in PKD1 may convey increased risk for FTGCT in addition to causing ADPKD.

Published
2017

50. Psychiatric neuroimaging designs for individualised, cohort, and population studies

Author

Gell, Martin, Noble, Stephanie, Laumann, Timothy O., Nelson, Steven M., and Tervo-Clemmens, Brenden

Abstract

Psychiatric neuroimaging faces challenges to rigour and reproducibility that prompt reconsideration of the relative strengths and limitations of study designs. Owing to high resource demands and varying inferential goals, current designs differentially emphasise sample size, measurement breadth, and longitudinal assessments. In this overview and perspective, we provide a guide to the current landscape of psychiatric neuroimaging study designs with respect to this balance of scientific goals and resource constraints. Through a heuristic data cube contrasting key design features, we discuss a resulting trade-off among small sample, precision longitudinal studies (e.g., individualised studies and cohorts) and large sample, minimally longitudinal, population studies. Precision studies support tests of within-person mechanisms, via intervention and tracking of longitudinal course. Population studies support tests of generalisation across multifaceted individual differences. A proposed reciprocal validation model (RVM) aims to recursively leverage these complementary designs in sequence to accumulate evidence, optimise relative strengths, and build towards improved long-term clinical utility.

Published
2024
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