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3. A 3D deep learning classifier and its explainability when assessing coronary artery disease

Author

Cheung, Wing Keung, Kalindjian, Jeremy, Bell, Robert, Nair, Arjun, Menezes, Leon J., Patel, Riyaz, Wan, Simon, Chou, Kacy, Chen, Jiahang, Torii, Ryo, Davies, Rhodri H., Moon, James C., Alexander, Daniel C., and Jacob, Joseph

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Machine Learning
Abstract

Early detection and diagnosis of coronary artery disease (CAD) could save lives and reduce healthcare costs. In this study, we propose a 3D Resnet-50 deep learning model to directly classify normal subjects and CAD patients on computed tomography coronary angiography images. Our proposed method outperforms a 2D Resnet-50 model by 23.65%. Explainability is also provided by using a Grad-GAM. Furthermore, we link the 3D CAD classification to a 2D two-class semantic segmentation for improved explainability and accurate abnormality localisation.

Published
2023

7. Shiga Toxin-Producing Escherichia coli Diagnoses from Health Practitioners, Queensland, Australia

Author

Shrestha, Ashish C., Stafford, Russell, Bell, Robert, Jennison, Amy V., Graham, Rikki M.A., Field, Emma, and Lambert, Stephen B.

Subjects
Infection -- Diagnosis, Health
Abstract

Shiga toxin-producing Escherichia coli (STEC) cause gastrointestinal illness and can result in hemolytic uremic syndrome (HUS) (1). Asymptomatic STEC infections can occur and might remain undetected (2,3), making the population [...]

Published
2024

8. Investigating the Electronic Structure of Prospective Water-splitting Oxide BaCe$_{0.25}$Mn$_{0.75}$O$_{3-\delta}$ Before and After Thermal Reduction

Author

Roychoudhury, Subhayan, Shulda, Sarah, Goyal, Anuj, Bell, Robert, Sainio, Sami, Strange, Nicholas, Park, James Eujin, Coker, Eric N., Lany, Stephan, Ginley, David, and Prendergast, David

Subjects
Condensed Matter - Materials Science
Abstract

BaCe$_{0.25}$Mn$_{0.75}$O$_{3-\delta}$ (BCM), a non-stoichiometric oxide closely resembling a perovskite crystal structure, has recently emerged as a prospective contender for application in renewable energy harvesting by solar thermochemical hydrogen generation. Using solar energy, oxygen-vacancies can be created in BCM and the reduced crystal so obtained can, in turn, produce H2 by stripping oxygen from H2O. Therefore, a first step toward understanding the working mechanism and optimizing the performance of BCM, is a thorough and comparative analysis of the electronic structure of the pristine and the reduced material. In this paper, we probe the electronic structure of BCM using the combined effort of first-principles calculations and experimental O K-edge x-ray absorption spectroscopy (XAS). The computed projected density-of-states (PDOS) and orbital-plots are used to propose a simplified model for orbital-mixing between the oxygen and the ligand atoms. With the help of state-of-the-art simulations, we are able to find the origins of the XAS peaks and to categorize them on the basis of contribution from Ce and Mn. For the reduced crystal, the calculations show that, as a consequence of dielectric screening, the change in electron-density resulting from the reduction is strongly localized around the oxygen vacancy. Our experimental studies reveal a marked lowering of the first O K-edge peak in the reduced crystal which is shown to result from a diminished O-2p contribution to the frontier unoccupied orbitals, in accordance with the tight-binding scheme. Our study paves the way for investigation of the working-mechanism of BCM and for computational and experimental efforts aimed at design and discovery of efficient water-splitting oxides.

Published
2022
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9. Characterizing the Processes for Navigating Internet Health Information Using Real-Time Observations: A Mixed-Methods Approach

Author

Perez, Susan L, Paterniti, Debora A, Wilson, Machelle, Bell, Robert A, Chan, Man Shan, Villareal, Chloe C, Nguyen, Hien Huy, and Kravitz, Richard L

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Public aspects of medicine, RA1-1270
Abstract

BackgroundLittle is known about the processes people use to find health-related information on the Internet or the individual characteristics that shape selection of information-seeking approaches. ObjectiveOur aim was to describe the processes by which users navigate the Internet for information about a hypothetical acute illness and to identify individual characteristics predictive of their information-seeking strategies. MethodsStudy participants were recruited from public settings and agencies. Interested individuals were screened for eligibility using an online questionnaire. Participants listened to one of two clinical scenarios—consistent with influenza or bacterial meningitis—and then conducted an Internet search. Screen-capture video software captured Internet search mouse clicks and keystrokes. Each step of the search was coded as hypothesis testing (etiology), evidence gathering (symptoms), or action/treatment seeking (behavior). The coded steps were used to form a step-by-step pattern of each participant’s information-seeking process. A total of 78 Internet health information seekers ranging from 21-35 years of age and who experienced barriers to accessing health care services participated. ResultsWe identified 27 unique patterns of information seeking, which were grouped into four overarching classifications based on the number of steps taken during the search, whether a pattern consisted of developing a hypothesis and exploring symptoms before ending the search or searching an action/treatment, and whether a pattern ended with action/treatment seeking. Applying dual-processing theory, we categorized the four overarching pattern classifications as either System 1 (41%, 32/78), unconscious, rapid, automatic, and high capacity processing; or System 2 (59%, 46/78), conscious, slow, and deliberative processing. Using multivariate regression, we found that System 2 processing was associated with higher education and younger age. ConclusionsWe identified and classified two approaches to processing Internet health information. System 2 processing, a methodical approach, most resembles the strategies for information processing that have been found in other studies to be associated with higher-quality decisions. We conclude that the quality of Internet health-information seeking could be improved through consumer education on methodical Internet navigation strategies and the incorporation of decision aids into health information websites.

Published
2015
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10. Parental COVID-19 Vaccine Hesitancy in the United States

Author

Ruiz, Jeanette B and Bell, Robert A

Subjects
Immunization, Vaccine Related, Pediatric, Prevention, 3.4 Vaccines, Prevention of disease and conditions, and promotion of well-being, Infection, Good Health and Well Being, Adolescent, COVID-19, COVID-19 Vaccines, Child, Female, Humans, Male, Parents, United States, Vaccination, Vaccination Hesitancy, Vaccines, children, coronavirus, vaccine, conspiracy beliefs, Nursing, Public Health and Health Services, Policy and Administration, Public Health
Abstract

ObjectiveLittle is known about parents' willingness to vaccinate their children against COVID-19. We assessed the prevalence of vaccine hesitancy among parents with a child or adolescent aged 12-15 years, examined predictors of parents' COVID-19 vaccine hesitancy, their reasons for resisting a pediatric COVID-19 vaccine, and the correlation between parents' intentions to vaccinate their child and the acceptance of a vaccine for themselves.MethodsWe conducted a national online survey of 637 parents of a child or adolescent aged 12-15 years in March 2021, before COVID-19 vaccines had been approved for this age group. We assessed univariate predictors of vaccine hesitancy, and we used logistic regression analysis to assess independent effects of variables on vaccine hesitancy.ResultsNearly one-third (28.9%; 95% CI, 25.5%-32.5%) of respondents reported pediatric vaccine hesitancy. Vaccine-hesitant parents were less knowledgeable about vaccines, more accepting of vaccine conspiracies, and less worried about COVID-19 risks to their child's health than vaccine-accepting parents were. Vaccine hesitancy was higher among female (vs male), single (vs married/living as married), older (vs younger), low income (vs high income), non-college graduates (vs college graduates), and Republican (vs Democrat) parents. The primary concerns expressed by vaccine-hesitant parents pertained to vaccine safety rather than vaccine effectiveness. One-quarter of vaccine-hesitant parents preferred that their child obtain immunity through infection rather than vaccination. Non-vaccine-hesitant parents' reasons for vaccinating focused on protecting the health of their child and others. Childhood COVID-19 vaccine acceptance was strongly associated with parents' intentions to get the vaccine for themselves.ConclusionA messaging strategy for effective public health interventions that includes educating the public about vaccination, countering misinformation about vaccine development and safety, and stressing the safety of approved COVID-19 vaccines may boost vaccine acceptance among vaccine-hesitant parents.

Published
2022

11. Ancestry-independent risk of venous thromboembolism in individuals with sickle cell trait vs factor V Leiden

Author

Aslibekyan, Stella, Auton, Adam, Babalola, Elizabeth, Bell, Robert K., Bielenberg, Jessica, Bowes, Jonathan, Bryc, Katarzyna, Chaudhary, Ninad S., Coker, Daniella, Das, Sayantan, DelloRusso, Emily, Elson, Sarah L., Eriksson, Nicholas, Filshtein, Teresa, Fontanillas, Pierre, Freyman, Will, Fuller, Zach, German, Chris, Granka, Julie M., Heilbron, Karl, Hernandez, Alejandro, Hicks, Barry, Hinds, David A., Jewett, Ethan M., Jiang, Yunxuan, Kukar, Katelyn, Kwong, Alan, Liang, Yanyu, Lin, Keng-Han, Llamas, Bianca A., McIntyre, Matthew H., Micheletti, Steven J., Moreno, Meghan E., Nandakumar, Priyanka, Nguyen, Dominique T., O'Connell, Jared, Petrakovitz, Aaron A., Poznik, G. David, Reynoso, Alexandra, Saini, Shubham, Schumacher, Morgan, Selcer, Leah, Shastri, Anjali J., Shelton, Janie F., Shi, Jingchunzi, Shringarpure, Suyash, Su, Qiaojuan Jane, Tat, Susana A., Tran, Vinh, Tung, Joyce Y., Wang, Xin, Wang, Wei, Weldon, Catherine H., Wilton, Peter, Wong, Corinna D., Bonham, Vence L., and Naik, Rakhi P.

Published
2024
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13. Cognitive and psychiatric symptom trajectories 2–3 years after hospital admission for COVID-19: a longitudinal, prospective cohort study in the UK

Author

Lone, Nazir, Baillie, Kenneth, Pairo-Castineira, Erola, Avramidis, Nikos, Wain, Louise, Guillen-Guio, Beatriz, Leavy, Olivia, Jones, S, Armstrong, Lisa, Hairsine, Brigid, Henson, Helen, Kurasz, Claire, Shaw, Alison, Shenton, Liz, Dobson, Hannah, Dell, Amanda, Fairbairn, Sara, Hawkings, Nancy, Haworth, Jill, Hoare, Michaela, Lewis, Victoria, Lucey, Alice, Mallison, Georgia, Nassa, Heeah, Pennington, Chris, Price, Andrea, Price, Claire, Storrie, Andrew, Willis, Gemma, Young, Susan, Poinasamy, Krisnah, Walker, Samantha, Jarrold, Ian, Rawlik, Konrad, Sanderson, Amy, Chong-James, K, David, C, James, W Y, Pfeffer, Paul, Zongo, O, Martineau, Adrian, Manisty, C, Armour, Cherie, Brown, Vanessa, Busby, John, Connolly, Bronwen, Craig, Thelma, Drain, Stephen, Heaney, Liam, King, Bernie, Magee, Nick, Major, E, McAulay, Danny, McGarvey, Lorcan, McGinness, Jade, Peto, Tunde, Stone, Roisin, Bolger, Annette, Davies, Ffyon, Haggar, Ahmed, Lewis, Joanne, Lloyd, Arwel, Manley, R, McIvor, Emma, Menzies, Daniel, Roberts, K, Saxon, W, Southern, David, Subbe, Christian, Whitehead, Victoria, Bularga, Anda, Mills, Nicholas, Dawson, Joy, El-Taweel, Hosni, Robinson, Leanne, Brear, Lucy, Regan, Karen, Saralaya, Dinesh, Storton, Kim, Amoils, Shannon, Bermperi, Areti, Cruz, Isabel, Dempsey, K, Elmer, Anne, Fuld, Jonathon, Jones, H, Jose, Sherly, Marciniak, Stefan, Parkes, M, Ribeiro, Carla, Taylor, Jessica, Toshner, Mark, Watson, L, Worsley, J, Broad, Lauren, Evans, Teriann, Haynes, Matthew, Jones, L, Knibbs, Lucy, McQueen, Alison, Oliver, Catherine, Paradowski, Kerry, Sabit, Ramsey, Williams, Jenny, Jones, Ian, Milligan, Lea, Harris, Edward, Sampson, Claire, Davies, Ellie, Evenden, Cerys, Hancock, Alyson, Hancock, Kia, Lynch, Ceri, Rees, Meryl, Roche, Lisa, Stroud, Natalie, Thomas-Woods, T, Heller, Simon, Chalder, Trudie, Shah, Kamini, Robertson, Elizabeth, Young, Bob, Babores, Marta, Holland, Maureen, Keenan, Natalie, Shashaa, Sharlene, Wassall, Helen, Austin, Liam, Beranova, Eva, Cosier, Tracey, Deery, Joanne, Hazelton, Tracy, Price, Carly, Ramos, Hazel, Solly, Reanne, Turney, Sharon, Weston, Heather, Coughlan, Eamon, Ralser, Markus, Pearce, Lorraine, Pugmire, S, Stoker, Wendy, Wilson, Ann, McCormick, W, Fraile, Eva, Ugoji, Jacinta, Aguilar Jimenez, Laura, Arbane, Gill, Betts, Sarah, Bisnauthsing, Karen, Dewar, A, Hart, Nicholas, Kaltsakas, G, Kerslake, Helen, Magtoto, Murphy, Marino, Philip, Martinez, L M, Ostermann, Marlies, Rossdale, Jennifer, Solano, Teresa, Alvarez Corral, Maria, Arias, Ava Maria, Bevan, Emily, Griffin, Denise, Martin, Jane, Owen, J, Payne, Sheila, Prabhu, A, Reed, Annabel, Storrar, Will, Williams, Nick, Wrey Brown, Caroline, Burdett, Tracy, Featherstone, James, Lawson, Cathy, Layton, Alison, Mills, Clare, Stephenson, Lorraine, Ellis, Yvette, Atkin, Paul, Brindle, K, Crooks, Michael, Drury, Katie, Easom, Nicholas, Flockton, Rachel, Holdsworth, L, Richards, A, Sykes, D L, Thackray-Nocera, Susannah, Wright, C, Coetzee, S, Davies, Kim, Hughes, Rachel Ann, Loosley, Ronda, McGuinness, Heather, Mohamed, Abdelrahman, O'Brien, Linda, Omar, Zohra, Perkins, Emma, Phipps, Janet, Ross, Gavin, Taylor, Abigail, Tench, Helen, Wolf-Roberts, Rebecca, Burden, L, Calvelo, Ellen, Card, Bethany, Carr, Caitlin, Chilvers, Edwin, Copeland, Donna, Cullinan, P, Daly, Patrick, Evison, Lynsey, Fayzan, Tamanah, Gordon, Hussain, Haq, Sulaimaan, Jenkins, Gisli, King, Clara, Kon, Onn Min, March, Katherine, Mariveles, Myril, McLeavey, Laura, Mohamed, Noura, Moriera, Silvia, Munawar, Unber, Nunag, Jose Lloyd, Nwanguma, Uchechi, Orriss-Dib, Lorna, Ross, Alexandra, Roy, Maura, Russell, Emily, Samuel, Katherine, Schronce, J, Simpson, Neil, Tarusan, Lawrence, Thomas, David, Wood, Chloe, Yasmin, Najira, Altmann, Danny, Howard, Luke, Johnston, Desmond, Lingford-Hughes, Anne, Man, William, Mitchell, Jane, Molyneaux, Philip, Nicolaou, Christos, O'Regan, D P, Price, L, Quint, Jenni, Smith, David, Thwaites, Ryan, Valabhji, Jonathon, Walsh, Simon, Efstathiou, Claudia, Liew, Felicity, Frankel, Anew, Lightstone, Liz, McAdoo, Steve, Wilkins, Martin, Willicombe, Michelle, Touyz, R, Guerdette, Anne-Marie, Hewitt, Melanie, Reddy, R, Warwick, Katie, White, Sonia, McMahon, Aisling, Adeyemi, Oluwaseun, Adrego, Rita, Assefa-Kebede, Hosanna, Breeze, Jonathon, Byrne, S, Dulawan, Pearl, Hoare, Amy, Jolley, Caroline, Knighton, Abigail, Patale, Sheetal, Peralta, Ida, Powell, Natassia, Ramos, Albert, Shevket, K, Speranza, Fabio, Te, Amelie, Malim, M, Bramham, Kate, Brown, M, Ismail, Khalida, Nicholson, Tim, Pariante, Carmen, Sharpe, Claire, Wessely, Simon, Whitney, J, Shah, Ajay, Chiribiri, A, O'Brien, C, Hayday, A, Ashworth, Andrew, Beirne, Paul, Clarke, Jude, Coupland, C, Dalton, Matthhew, Favager, Clair, Glossop, Jodie, Greenwood, John, Hall, Lucy, Hardy, Tim, Humphries, Amy, Murira, Jennifer, Peckham, Dan, Plein, S, Rangeley, Jade, Saalmink, Gwen, Tan, Ai Lyn, Wade, Elaine, Whittam, Beverley, Window, Nicola, Woods, Janet, Coakley, G, Turtle, Lance, Allerton, Lisa, Allt, Ann Marie, Beadsworth, M, Berridge, Anthony, Brown, Jo, Cooper, Shirley, Cross, Andy, Defres, Sylviane, Dobson, S L, Earley, Joanne, French, N, Greenhalf, William, Hainey, Kera, Hardwick, Hayley, Hawkes, Jenny, Highett, Victoria, Kaprowska, Sabina, Key, Angela, Lavelle-Langham, Lara, Lewis-Burke, N, Madzamba, Gladys, Malein, Flora, Marsh, Sophie, Mears, Chloe, Melling, Lucy, Noonan, Matthew, Poll, L, Pratt, James, Richardson, Emma, Rowe, Anna, Semple, Calum, Shaw, Victoria, Tripp, K A, Wajero, Lilian, Williams-Howard, S A, Wootton, Dan, Wyles, J, Diwanji, Shalin, Gurram, Sambasivarao, Papineni, Padmasayee, Quaid, Sheena, Tiongson, Gerlynn, Watson, Ekaterina, Briggs, Andrew, Marks, Michael, Hastie, Claire, Rogers, Natalie, Smith, Nikki, Stensel, David, Bishop, Lettie, McIvor, Katherine, Rivera-Ortega, Pilar, Al-Sheklly, Bashar, Avram, Cristina, Blaikely, John, Buch, M, Choudhury, N, Faluyi, David, Felton, T, Gorsuch, T, Hanley, Neil, Horsley, Alex, Hussell, Tracy, Kausar, Zunaira, Odell, Natasha, Osbourne, Rebecca, Piper Hanley, Karen, Radhakrishnan, K, Stockdale, Sue, Kabir, Thomas, Scott, Janet, Stewart, Iain, Openshaw, Peter, Burn, David, Ayoub, A, Brown, J, Burns, G, Davies, Gareth, De Soyza, Anthony, Echevarria, Carlos, Fisher, Helen, Francis, C, Greenhalgh, Alan, Hogarth, Philip, Hughes, Joan, Jiwa, Kasim, Jones, G, MacGowan, G, Price, D, Sayer, Avan, Simpson, John, Tedd, H, Thomas, S, West, Sophie, Witham, M, Wright, S, Young, A, McMahon, Michael, Neill, Paula, Anderson, David, Basu, Neil, Bayes, Hannah, Brown, Ammani, Dougherty, Andrew, Fallon, K, Gilmour, L, Grieve, D, Mangion, K, Morrow, A, Sykes, R, Berry, Colin, McInnes, I B, Scott, Kathryn, Barrett, Fiona, Donaldson, A, Sage, Beth, Bell, Murdina, Brown, Angela, Hamil, R, Leitch, Karen, Macliver, L, Patel, Manish, Quigley, Jackie, Smith, Andrew, Welsh, B, Choudhury, Gaunab, Clohisey, S, Deans, Andrew, Docherty, Annemarie, Furniss, J, Harrison, Ewen, Kelly, S, Sheikh, Aziz, Chalmers, James, Connell, David, Deas, C, Elliott, Anne, George, J, Mohammed, S, Rowland, J, Solstice, AR, Sutherland, Debbie, Tee, Caroline, Bunker, Jenny, Gill, Rhyan, Nathu, Rashmita, Holmes, Katie, Adamali, H, Arnold, David, Barratt, Shaney, Dipper, A, Dunn, Sarah, Maskell, Nick, Morley, Anna, Morrison, Leigh, Stadon, Louise, Waterson, Samuel, Welch, H, Jayaraman, Bhagy, Light, Tessa, Vogiatzis, Ioannis, Almeida, Paula, Bolton, Charlotte, Hosseini, Akram, Matthews, Laura, Needham, Robert, Shaw, Karen, Thomas, Andrew, Bonnington, J, Chrystal, Melanie, Dupont, Catherine, Greenhaff, Paul, Gupta, Ayushman, Jang, W, Linford, S, Nikolaidis, Athanasios, Prosper, Sabrina, Burns, A, Kanellakis, N, Ferreira, V, Nikolaidou, C, Xie, C, Ainsworth, Mark, Alamoudi, Asma, Bloss, Angela, Carter, Penny, Cassar, M, Chen, Jin, Conneh, Florence, Dong, T, Evans, Ranuromanana, Fraser, Emily, Geddes, John, Gleeson, F, Harrison, Paul, Havinden-Williams, May, Ho, Ling Pei, Jezzard, P, Koychev, Ivan, Kurupati, Prathiba, McShane, H, Megson, Clare, Neubauer, Stefan, Nicoll, Debby, Ogg, G, Pacpaco, Edmund, Pavlides, M, Peng, Yanchun, Petousi, Nayia, Pimm, John, Rahman, Najib, Raman, Betty, Rowland, M J, Saunders, Kathryn, Sharpe, Michael, Talbot, Nick, Tunnicliffe, E M, Korszun, Ania, Kerr, Steven, Barker, R E, Cristiano, Daniele, Dormand, N, George, P, Gummadi, Mahitha, Kon, S, Liyanage, Kamal, Nolan, C M, Patel, B, Patel, Suhani, Polgar, Oliver, Shah, P, Singh, Suver, Walsh, J A, Gibbons, Michael, Ahmad, Shanaz, Brill, Simon, Hurst, John, Jarvis, Hannah, Lim, Lai, Mandal, S, Matila, Darwin, Olaosebikan, Olaoluwa, Singh, Claire, Laing, C, Baxendale, Helen, Garner, Lucie, Johnson, C, Mackie, J, Michael, Alice, Newman, J, Pack, Jamie, Paques, K, Parfrey, H, Parmar, J, Reddy, A, Halling-Brown, Mark, Dark, P, Diar-Bakerly, Nawar, Evans, D, Hardy, E, Harvey, Alice, Holgate, D, Knight, Sean, Mairs, N, Majeed, N, McMorrow, L, Oxton, J, Pendlebury, Jessica, Summersgill, C, Ugwuoke, R, Whittaker, S, Matimba-Mupaya, Wadzanai, Strong-Sheldrake, Sophia, Chowienczyk, Phillip, Bagshaw, J, Begum, M, Birchall, K, Butcher, Robyn, Carborn, H, Chan, Flora, Chapman, Kerry, Cheng, Yutung, Chetham, Luke, Clark, Cameron, Coburn, Zach, Cole, Joby, Dixon, Myles, Fairman, Alexandra, Finnigan, J, Foot, H, Foote, David, Ford, Amber, Gregory, Rebecca, Harrington, Kate, Haslam, L, Hesselden, L, Hockridge, J, Holbourn, Ailsa, Holroyd-Hind, B, Holt, L, Howell, Alice, Hurditch, E, Ilyas, F, Jarman, Claire, Lawrie, Allan, Lee, Ju Hee, Lee, Elvina, Lenagh, Rebecca, Lye, Alison, Macharia, Irene, Marshall, M, Mbuyisa, Angeline, McNeill, J, Megson, Sharon, Meiring, J, Milner, L, Misra, S, Newell, Helen, Newman, Tom, Norman, C, Nwafor, Lorenza, Pattenadk, Dibya, Plowright, Megan, Porter, Julie, Ravencroft, Phillip, Roddis, C, Rodger, J, Rowland-Jones, Sarah, Saunders, Peter, Sidebottom, J, Smith, Jacqui, Smith, Laurie, Steele, N, Stephens, G, Stimpson, R, Thamu, B, Thompson, A. A. Roger, Tinker, N, Turner, Kim, Turton, Helena, Wade, Phillip, Walker, S, Watson, James, Wilson, Imogen, Zawia, Amira, Allsop, Lynne, Bennett, Kaytie, Buckley, Phil, Flynn, Margaret, Gill, Mandy, Goodwin, Camelia, Greatorex, M, Gregory, Heidi, Heeley, Cheryl, Holloway, Leah, Holmes, Megan, Hutchinson, John, Kirk, Jill, Lovegrove, Wayne, Sewell, Terri Ann, Shelton, Sarah, Sissons, D, Slack, Katie, Smith, Susan, Sowter, D, Turner, Sarah, Whitworth, V, Wynter, Inez, Tomlinson, Johanne, Warburton, Louise, Painter, Sharon, Palmer, Sue, Redwood, Dawn, Tilley, Jo, Vickers, Carinna, Wainwright, Tania, Breen, G, Hotopf, M, Aul, Raminder, Forton, D, Ali, Mariam, Dunleavy, A, Mencias, Mark, Msimanga, N, Samakomva, T, Siddique, Sulman, Tavoukjian, Vera, Teixeira, J, Ahmed, Rubina, Francis, Richard, Connor, Lynda, Cook, Amanda, Davies, Gwyneth, Rees, Tabitha, Thaivalappil, Favas, Thomas, Caradog, McNarry, M, Williams, N, Lewis, Keir, Coulding, Martina, Jones, Heather, Kilroy, Susan, McCormick, Jacqueline, McIntosh, Jerome, Turner, Victoria, Vere, Joanne, Butt, Al-Tahoor, Savill, Heather, Kon, Samantha, Landers, G, Lota, Harpreet, Portukhay, Sofiya, Nasseri, Mariam, Daniels, Alison, Hormis, Anil, Ingham, Julie, Zeidan, Lisa, Chablani, Manish, Osborne, Lynn, Aslani, Shahab, Banerjee, Amita, Batterham, R, Baxter, Gabrielle, Bell, Robert, David, Anthony, Denneny, Emma, Hughes, Alun, Lilaonitkul, W, Mehta, P, Pakzad, Ashkan, Rangelov, Bojidar, Williams, B, Willoughby, James, Xu, Moucheng, Ahwireng, Nyarko, Bang, Dongchun, Basire, Donna, Brown, Jeremy, Chambers, Rachel, Checkley, A, Evans, R, Heightman, M, Hillman, T, Jacob, Joseph, Jastrub, Roman, Lipman, M, Logan, S, Lomas, D, Merida Morillas, Marta, Plant, Hannah, Porter, Joanna, Roy, K, Wall, E, Treibel, T, Ahmad Haider, N, Atkin, Catherine, Baggott, Rhiannon, Bates, Michelle, Botkai, A, Casey, Anna, Cooper, B, Dasgin, Joanne, Dawson, Camilla, Draxlbauer, Katharine, Gautam, N, Hazeldine, J, Hiwot, T, Holden, Sophie, Isaacs, Karen, Jackson, T, Kamwa, Vicky, Lewis, D, Lord, Janet, Madathil, S, McGee, C, Mcgee, K, Neal, Aoife, Newton-Cox, Alex, Nyaboko, Joseph, Parekh, Dhruv, Peterkin, Z, Qureshi, H, Ratcliffe, Liz, Sapey, Elizabeth, Short, J, Soulsby, Tracy, Stockley, J, Suleiman, Zehra, Thompson, Tamika, Ventura, Maximina, Walder, Sinead, Welch, Carly, Wilson, Daisy, Yasmin, S, Yip, Kay Por, Chaudhuri, N, Childs, Caroline, Djukanovic, R, Fletcher, S, Harvey, Matt, Jones, Mark, Marouzet, Elizabeth, Marshall, B, Samuel, Reena, Sass, T, Wallis, Tim, Wheeler, Helen, Steeds, R, Beckett, Paul, Dickens, Caroline, Nanda, Uttam, Aljaroof, M, Armstrong, Natalie, Arnold, H, Aung, Hnin, Bakali, Majda, Bakau, M, Baldry, E, Baldwin, Molly, Bourne, Charlotte, Bourne, Michelle, Brightling, Chris, Brunskill, Nigel, Cairns, P, Carr, Liesel, Charalambou, Amanda, Christie, C, Davies, Melanie, Daynes, Enya, Diver, Sarah, Dowling, Rachael, Edwards, Sarah, Edwardson, C, Elneima, Omer, Evans, H, Evans, Rachael, Finch, J, Glover, Sarah, Goodman, Nicola, Gooptu, Bibek, Greening, Neil, Hadley, Kate, Haldar, Pranab, Hargadon, Beverley, Harris, Victoria, Houchen-Wolloff, Linzy, Ibrahim, W, Ingram, L, Khunti, Kamlesh, Lea, A, Lee, D, McAuley, Hamish, McCann, Gerry, McCourt, P, Mcnally, Teresa, Mills, George, Monteiro, Will, Pareek, Manish, Parker, S, Prickett, Anne, Qureshi, I N, Rowland, A, Russell, Richard, Sereno, Marco, Shikotra, Aarti, Siddiqui, Salman, Singapuri, Ananga, Singh, Sally, Skeemer, J, Soares, M, Stringer, E, Thornton, T, Tobin, Martin, Ward, T J C, Woodhead, F, Yates, Tom, Yousuf, A J, Broome, Mattew, McArdle, Paul, Thickett, David, Upthegrove, Rachel, Wilkinson, Dan, Moss, Paul, Wraith, David, Evans, Jonathon, Bullmore, Ed, Heeney, Jonathon, Langenberg, Claudia, Schwaeble, William, Summers, Charlotte, Weir McCall, J, Adeloye, Davies, Newby, D E, Pius, Riinu, Rudan, Igor, Shankar-Hari, Manu, Sudlow, Catherine, Thorpe, Mat, Walmsley, Sarah, Zheng, Bang, Allan, Louise, Ballard, Clive, McGovern, Andrew, Dennis, J, Cavanagh, Jonathon, MacDonald, S, O'Donnell, Kate, Petrie, John, Sattar, Naveed, Spears, Mark, Guthrie, Elspeth, Henderson, Max, Allen, Richard, Bingham, Michelle, Brugha, Terry, Finney, Selina, Free, Rob, Jones, Don, Lawson, Claire, Lucy, Gardiner, Moss, Alistair, Mukaetova-Ladinska, Elizabeta, Novotny, Petr, Overton, Charlotte, Pearl, John, Plekhanova, Tatiana, Richardson, M, Samani, Nilesh, Sargant, Jack, Sharma, M, Steiner, Mike, Taylor, Chris, Terry, Sarah, Tong, C, Turner, E, Wormleighton, J, Zhao, Bang, Ntotsis, Kimon, Saunders, Ruth, Lozano-Rojas, Daniel, Goemans, Anne, Cuthbertson, D, Kemp, G, McArdle, Anne, Michael, Benedict, Reynolds, Will, Spencer, Lisa, Vinson, Ben, Ashworth, M, Abel, Kathryn, Chinoy, H, Deakin, Bill, Harvie, M, Miller, C A, Stanel, Stefan, Barran, Perdita, Trivedi, Drupad, McAllister-Williams, Hamish, Paddick, Stella-Maria, Rostron, Anthony, Taylor, John Paul, Baguley, David, Coleman, Chris, Cox, E, Fabbri, Laura, Francis, Susan, Hall, Ian, Hufton, E, Johnson, Simon, Khan, Fasih, Kitterick, Paaig, Morriss, Richard, Selby, Nick, Wright, Louise, Antoniades, Charalambos, Bates, A, Beggs, M, Bhui, Kamaldeep, Breeze, Katie, Channon, K M, Clark, David, Fu, X, Husain, Masud, Li, X, Lukaschuk, E, McCracken, Celeste, McGlynn, K, Menke, R, Motohashi, K, Nichols, T E, Ogbole, Godwin, Piechnik, S, Propescu, I, Propescu, J, Samat, A A, Sanders, Z B, Sigfrid, Louise, Webster, M, Kingham, Lucy, Klenerman, Paul, Lamlum, Hanan, Taquet, Maxime, Carson, G, Finnigan, L, Saunders, Laura, Wild, James, Calder, P C, Huneke, Nathan, Simons, Gemma, Baldwin, David, Bain, Steve, Daines, Luke, Bright, E, Crisp, P, Dharmagunawardena, Ruvini, Stern, M, Bailey, Elisabeth, Reddington, Anne, Wight, Andrew, Ashish, A, Cooper, Josh, Robinson, Emma, Broadley, Andrew, Barman, Laura, Brookes, Claire, Elliott, K, Griffiths, L, Guy, Zoe, Howard, Kate, Ionita, Diana, Redfearn, Heidi, Sarginson, Carol, Turnbull, Alison, Skorniewska, Zuzanna, De Deyn, Thomas, Hampshire, Adam, Trender, William R, Hellyer, Peter J, Chalmers, James D, Ho, Ling-Pei, Leavy, Olivia C, Richardson, Matthew, McAuley, Hamish J C, Singapuri, Amisha, Saunders, Ruth M, Harris, Victoria C, Greening, Neil J, Mansoori, Parisa, Harrison, Ewen M, Docherty, Annemarie B, Lone, Nazir I, Quint, Jennifer, Brightling, Christopher E, Wain, Louise V, Evans, Rachael A, Geddes, John R, and Harrison, Paul J

Published
2024
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14. Status of global coastal adaptation

Author

Magnan, Alexandre K., Bell, Robert, Duvat, Virginie K. E., Ford, James D., Garschagen, Matthias, Haasnoot, Marjolijn, Lacambra, Carmen, Losada, Inigo J., Mach, Katharine J., Noblet, Mélinda, Parthasaranthy, Devanathan, Sano, Marcello, Vincent, Katharine, Anisimov, Ariadna, Hanson, Susan, Malmström, Alexandra, Nicholls, Robert J., and Winter, Gundula

Published
2023
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16. The solute carrier SLC7A1 may act as a protein transporter at the blood-brain barrier

Author

Kurtyka, Magdalena, Wessely, Frank, Bau, Sarah, Ifie, Eseoghene, He, Liqun, de Wit, Nienke M., Pedersen, Alberte Bay Villekjær, Keller, Maximilian, Webber, Caleb, de Vries, Helga E., Ansorge, Olaf, Betsholtz, Christer, De Bock, Marijke, Chaves, Catarina, Brodin, Birger, Nielsen, Morten S., Neuhaus, Winfried, Bell, Robert D., Letoha, Tamás, Meyer, Axel H., Leparc, Germán, Lenter, Martin, Lesuisse, Dominique, Cader, Zameel M., Buckley, Stephen T., Loryan, Irena, and Pietrzik, Claus U.

Published
2024
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19. A Pedagogical Introduction to Holographic Hadrons

Author

Domokos, Sophia K, Bell, Robert, La, Trinh, and Mazza, Patrick

Subjects
High Energy Physics - Theory, High Energy Physics - Phenomenology
Abstract

String theory's holographic QCD duality makes predictions for hadron physics by building models that live in five-dimensional (5D) curved space. In this pedagogical note, we explain how finding the hadron mass spectrum in these models amounts to finding the eigenvalues of a time-independent, one-dimensional Schroedinger equation. Changing the structure of the 5D curved space is equivalent to altering the potential in the Schroedinger equation, which in turn alters the hadron spectrum. We illustrate this concept with three holographic QCD models possessing exact analogs in basic quantum mechanics: the free particle, the infinite square well, and the harmonic oscillator. In addition to making aspects of holographic QCD accessible to undergraduates, this formulation can provide students with intuition for the meaning of curved space. This paper is intended primarily as a tool for researchers interested in involving early-stage undergraduates in research, but is also a suitable introduction to elements of holographic QCD for advanced undergraduate- and beginning graduate students with some knowledge of general relativity and classical field theory., Comment: 12 pages, 4 figures, a slightly revised version has been submitted to the European Journal of Physics

Published
2021

20. A phenome-wide association and Mendelian randomisation study of alcohol use variants in a diverse cohort comprising over 3 million individuals

Author

Aslibekyan, Stella, Auton, Adam, Babalola, Elizabeth, Bell, Robert K., Bielenberg, Jessica, Bryc, Katarzyna, Bullis, Emily, Coker, Daniella, Partida, Gabriel Cuellar, Dhamija, Devika, Das, Sayantan, Elson, Sarah L., Eriksson, Nicholas, Filshtein, Teresa, Fitch, Alison, Fletez-Brant, Kipper, Fontanillas, Pierre, Freyman, Will, Granka, Julie M., Heilbron, Karl, Hernandez, Alejandro, Hicks, Barry, Hinds, David A., Jewett, Ethan M., Jiang, Yunxuan, Kukar, Katelyn, Kwong, Alan, Lin, Keng-Han, Llamas, Bianca A., Lowe, Maya, McCreight, Jey C., McIntyre, Matthew H., Micheletti, Steven J., Moreno, Meghan E., Nandakumar, Priyanka, Nguyen, Dominique T., Noblin, Elizabeth S., O'Connell, Jared, Petrakovitz, Aaron A., Poznik, G. David, Reynoso, Alexandra, Schumacher, Morgan, Shastri, Anjali J., Shelton, Janie F., Shi, Jingchunzi, Shringarpure, Suyash, Su, Qiaojuan Jane, Tat, Susana A., Tchakouté, Christophe Toukam, Tran, Vinh, Tung, Joyce Y., Wang, Xin, Wang, Wei, Weldon, Catherine H., Wilton, Peter, Wong, Corinna D., Jennings, Mariela V., Martínez-Magaña, José Jaime, Courchesne-Krak, Natasia S., Cupertino, Renata B., Vilar-Ribó, Laura, Bianchi, Sevim B., Hatoum, Alexander S., Atkinson, Elizabeth G., Giusti-Rodriguez, Paola, Montalvo-Ortiz, Janitza L., Gelernter, Joel, Artigas, María Soler, Edenberg, Howard J., Palmer, Abraham A., and Sanchez-Roige, Sandra

Published
2024
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21. MUSSEL: Enhanced Bayesian polygenic risk prediction leveraging information across multiple ancestry groups

Author

Aslibekyan, Stella, Auton, Adam, Babalola, Elizabeth, Bell, Robert K., Bielenberg, Jessica, Bryc, Katarzyna, Bullis, Emily, Coker, Daniella, Cuellar Partida, Gabriel, Dhamija, Devika, Das, Sayantan, Elson, Sarah L., Eriksson, Nicholas, Filshtein, Teresa, Fitch, Alison, Fletez-Brant, Kipper, Fontanillas, Pierre, Freyman, Will, Granka, Julie M., Heilbron, Karl, Hernandez, Alejandro, Hicks, Barry, Hinds, David A., Jewett, Ethan M., Jiang, Yunxuan, Kukar, Katelyn, Kwong, Alan, Lin, Keng-Han, Llamas, Bianca A., Lowe, Maya, McCreight, Jey C., McIntyre, Matthew H., Micheletti, Steven J., Moreno, Meghan E., Nandakumar, Priyanka, Nguyen, Dominique T., Noblin, Elizabeth S., O’Connell, Jared, Petrakovitz, Aaron A., Poznik, G. David, Reynoso, Alexandra, Schumacher, Morgan, Shastri, Anjali J., Shelton, Janie F., Shi, Jingchunzi, Shringarpure, Suyash, Su, Qiaojuan Jane, Tat, Susana A., Tchakouté, Christophe Toukam, Tran, Vinh, Tung, Joyce Y., Wang, Xin, Wang, Wei, Weldon, Catherine H., Wilton, Peter, Wong, Corinna D., Jin, Jin, Zhan, Jianan, Zhang, Jingning, Zhao, Ruzhang, Buyske, Steven, Gignoux, Christopher, Haiman, Christopher, Kenny, Eimear E., Kooperberg, Charles, North, Kari, Koelsch, Bertram L., Wojcik, Genevieve, Zhang, Haoyu, and Chatterjee, Nilanjan

Published
2024
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23. Health position paper and redox perspectives on reactive oxygen species as signals and targets of cardioprotection

Author

Heusch, Gerd, Andreadou, Ioanna, Bell, Robert, Bertero, Edoardo, Botker, Hans-Erik, Davidson, Sean M., Downey, James, Eaton, Philip, Ferdinandy, Peter, Gersh, Bernard J., Giacca, Mauro, Hausenloy, Derek J., Ibanez, Borja, Krieg, Thomas, Maack, Christoph, Schulz, Rainer, Sellke, Frank, Shah, Ajay M., Thiele, Holger, Yellon, Derek M., and Di Lisa, Fabio

Published
2023
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24. Expedited transfer to a cardiac arrest centre for non-ST-elevation out-of-hospital cardiac arrest (ARREST): a UK prospective, multicentre, parallel, randomised clinical trial

Author

Perera, Divaka, Clapp, Brian, Prendergast, Bernard, Pavlidis, Antonis, Wragg, Andrew, Byrne, Jonathan, Stephens, Nigel, Rosser, Gareth, Wood, Darryl, Bell, Robert, Kurbaan, Arvinder, Ozkor, Muhiddin, Lampard, Anthony, Papadopoulos, Desiree, Hughes, Johanna, Pendolino, Valentina, Shaw, Joanna, Bannister, Clara, Long, Amy, Kearney, Justin, Palti, Gabriel, Ritches-Price, Joanne, Whitbread, Mark, Adamson, Dawn, Blows, Lucy, Brown, Martin, Lane, Garth, Connor, Michael, Muir, Keith, Chamberlain, Douglas, Morris, Tim, Kwok, Matthew, Knight, Megan, Jerome, Lauren, Nijjer, Sukhjinder, Das, Rita, Sidney, Therese, Bogle, Richard, Roberts, Patrick, Webb, Ian, Spencer, Oliver, Petzer, Edward, Khan, Masood, Marciniak, Maciej, De Belder, Mark, Stables, Rod, Curzen, Nick, Mamas, Mamas, Patterson, Tiffany, Perkins, Gavin D, Perkins, Alexander, Clayton, Tim, Evans, Richard, Dodd, Matthew, Robertson, Steven, Wilson, Karen, Mellett-Smith, Adam, Fothergill, Rachael T, McCrone, Paul, Dalby, Miles, MacCarthy, Philip, Firoozi, Sam, Malik, Iqbal, Rakhit, Roby, Jain, Ajay, Nolan, Jerry P, and Redwood, Simon R

Published
2023
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25. Predictors of intention to vaccinate against COVID-19: Results of a nationwide survey.

Author

Ruiz, Jeanette B and Bell, Robert A

Subjects
Humans, Vaccination, Intention, Adolescent, Adult, Aged, Middle Aged, United States, Female, Male, Young Adult, Surveys and Questionnaires, COVID-19, COVID-19 Vaccines, Conspiracy beliefs, Coronavirus, Media, Social media, Vaccine, Vaccine Related, Infectious Diseases, Immunization, Clinical Research, Influenza, Prevention, Biodefense, Emerging Infectious Diseases, Prevention of disease and conditions, and promotion of well-being, 3.4 Vaccines, Good Health and Well Being, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology
Abstract

BackgroundPublic polling indicates that vaccine uptake will be suboptimal when COVID-19 vaccines become available. Formative research seeking an understanding of weak vaccination intentions is urgently needed.MethodsNationwide online survey of 804 U.S. English-speaking adults. Compensated participants were recruited from the U.S. through an internet survey panel of 2.5 million residents developed by a commercial survey firm. Recruitment was based on quota sampling to produce a U.S. Census-matched sample representative of the nation with regard to region of residence, sex, and age.ResultsCOVID-19 vaccination intentions were weak, with 14.8% of respondents being unlikely to get vaccinated and another 23.0% unsure. Intent to vaccinate was highest for men, older people, individuals who identified as white and non-Hispanic, the affluent and college-educated, Democrats, those who were married or partnered, people with pre-existing medical conditions, and those vaccinated against influenza during the 2019-2020 flu season. In a multiple linear regression, significant predictors of vaccination intent were general vaccine knowledge (β = 0.311, p

Published
2021

26. Stress and corticotropin releasing factor (CRF) promote necrotizing enterocolitis in a formula-fed neonatal rat model

Author

Bell, Robert L, Withers, Ginger S, Kuypers, Frans A, Stehr, Wolfgang, and Bhargava, Aditi

Subjects
Paediatrics, Biomedical and Clinical Sciences, Perinatal Period - Conditions Originating in Perinatal Period, Pediatric, Preterm, Low Birth Weight and Health of the Newborn, Prevention, Infant Mortality, Rare Diseases, Good Health and Well Being, Animals, Animals, Newborn, Corticotropin-Releasing Hormone, Disease Models, Animal, Enterocolitis, Necrotizing, Infant Formula, Stress, Physiological, General Science & Technology
Abstract

The etiology of necrotizing enterocolitis (NEC) is not known. Alterations in gut microbiome, mucosal barrier function, immune cell activation, and blood flow are characterized events in its development, with stress as a contributing factor. The hormone corticotropin-releasing factor (CRF) is a key mediator of stress responses and influences these aforementioned processes. CRF signaling is modulated by NEC's main risk factors of prematurity and formula feeding. Using an established neonatal rat model of NEC, we tested hypotheses that: (i) increased CRF levels-as seen during stress-promote NEC in formula-fed (FF) newborn rats, and (ii) antagonism of CRF action ameliorates NEC. Newborn pups were formula-fed to initiate gut inflammation and randomized to: no stress, no stress with subcutaneous CRF administration, stress (acute hypoxia followed by cold exposure-NEC model), or stress after pretreatment with the CRF peptide antagonist Astressin. Dam-fed unstressed and stressed littermates served as controls. NEC incidence and severity in the terminal ileum were determined using a histologic scoring system. Changes in CRF, CRF receptor (CRFRs), and toll-like receptor 4 (TLR4) expression levels were determined by immunofluorescence and immunoblotting, respectively. Stress exposure in FF neonates resulted in 40.0% NEC incidence, whereas exogenous CRF administration resulted in 51.7% NEC incidence compared to 8.7% in FF non-stressed neonates (p

Published
2021

28. Well-Differentiated Papillary Mesothelioma of the Peritoneum Is Genetically Distinct from Malignant Mesothelioma

Author

Shrestha, Raunak, Nabavi, Noushin, Volik, Stanislav, Anderson, Shawn, Haegert, Anne, McConeghy, Brian, Sar, Funda, Brahmbhatt, Sonal, Bell, Robert, Le Bihan, Stephane, Wang, Yuzhuo, Collins, Colin, and Churg, Andrew

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Cancer, well-differentiated papillary mesothelioma, WDPM, malignant mesothelioma, DNA sequencing, mutation, Oncology and carcinogenesis
Abstract

Well-differentiated papillary mesothelioma (WDPM) is an uncommon mesothelial proliferation that is most commonly encountered as an incidental finding in the peritoneal cavity. There is controversy in the literature about whether WDPM is a neoplasm or a reactive process and, if neoplastic, whether it is a variant or precursor of epithelial malignant mesothelioma or is a different entity. Using whole exome sequencing of five WDPMs of the peritoneum, we have identified distinct mutations in EHD1, ATM, FBXO10, SH2D2A, CDH5, MAGED1, and TP73 shared by WDPM cases but not reported in malignant mesotheliomas. Furthermore, we show that WDPM is strongly enriched with C > A transversion substitution mutations, a pattern that is also not found in malignant mesotheliomas. The WDPMs lacked the alterations involving BAP1, SETD2, NF2, CDKN2A/B, LASTS1/2, PBRM1, and SMARCC1 that are frequently found in malignant mesotheliomas. We conclude that WDPMs are neoplasms that are genetically distinct from malignant mesotheliomas and, based on observed mutations, do not appear to be precursors of malignant mesotheliomas.

Published
2020

29. Identification of gene signature for treatment response to guide precision oncology in clear-cell renal cell carcinoma

Author

D’Costa, Ninadh M, Cina, Davide, Shrestha, Raunak, Bell, Robert H, Lin, Yen-Yi, Asghari, Hossein, Monjaras-Avila, Cesar U, Kollmannsberger, Christian, Hach, Faraz, Chavez-Munoz, Claudia I, and So, Alan I

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Immunology, Kidney Disease, Biotechnology, Cancer, Clinical Research, Genetics, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, 4.2 Evaluation of markers and technologies, Good Health and Well Being, Angiogenesis Inhibitors, Antineoplastic Agents, Immunological, Biomarkers, Tumor, Carcinoma, Renal Cell, Clinical Decision-Making, Cluster Analysis, Cohort Studies, Datasets as Topic, Feasibility Studies, Female, Gene Expression Profiling, Humans, Kidney Neoplasms, Male, Medical Oncology, Middle Aged, Patient Selection, Precision Medicine, Prognosis, Transcriptome
Abstract

Clear-cell renal cell carcinoma (ccRCC) is a common therapy resistant disease with aberrant angiogenic and immunosuppressive features. Patients with metastatic disease are treated with targeted therapies based on clinical features: low-risk patients are usually treated with anti-angiogenic drugs and intermediate/high-risk patients with immune therapy. However, there are no biomarkers available to guide treatment choice for these patients. A recently published phase II clinical trial observed a correlation between ccRCC patients' clustering and their response to targeted therapy. However, the clustering of these groups was not distinct. Here, we analyzed the gene expression profile of 469 ccRCC patients, using featured selection technique, and have developed a refined 66-gene signature for improved sub-classification of patients. Moreover, we have identified a novel comprehensive expression profile to distinguish between migratory stromal and immune cells. Furthermore, the proposed 66-gene signature was validated using a different cohort of 64 ccRCC patients. These findings are foundational for the development of reliable biomarkers that may guide treatment decision-making and improve therapy response in ccRCC patients.

Published
2020

31. Considerations When Developing Blood–Brain Barrier Crossing Drug Delivery Technology

Author

Bell, Robert D., Barrett, James E., Editor-in-Chief, Flockerzi, Veit, Editorial Board Member, Frohman, Michael A., Editorial Board Member, Geppetti, Pierangelo, Editorial Board Member, Hofmann, Franz B., Editorial Board Member, Kuner, Rohini, Editorial Board Member, Michel, Martin C., Editorial Board Member, Page, Clive P., Editorial Board Member, Wang, KeWei, Editorial Board Member, Cader, Zameel, editor, and Neuhaus, Winfried, editor

Published
2022
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33. Quasi-positivity and recognition of products of conjugacy classes in free groups

Author

Bell, Robert W. and Gitik, Rita

Subjects
Mathematics - Group Theory, Mathematics - Geometric Topology, 20E05, 20E45, 20F10, 68Q25
Abstract

Given a group $G$ and a subset $X \subset G$, an element $g \in G$ is called quasi-positive if it is equal to a product of conjugates of elements in the semigroup generated by $X$. This notion is important in the context of braid groups, where it has been shown that the closure of quasi-positive braids coincides with the geometrically defined class of $\mathbb{C}$-transverse links. We describe an algorithm that recognizes whether or not an element of a free group is quasi-positive with respect to a basis. Spherical cancellation diagrams over free groups are used to establish the validity of the algorithm and to determine the worst-case runtime., Comment: 15 pages, 2 figures. Revisions: References work of Orevkov; compares his and our methods

Published
2018

34. Saturation mutagenesis of twenty disease-associated regulatory elements at single base-pair resolution.

Author

Kircher, Martin, Xiong, Chenling, Martin, Beth, Schubach, Max, Inoue, Fumitaka, Bell, Robert JA, Costello, Joseph F, Shendure, Jay, and Ahituv, Nadav

Subjects
Cell Line, Humans, Disease, Cloning, Molecular, Computational Biology, Mutagenesis, Polymorphism, Single Nucleotide, Genomic Library, Genome, Human, Regulatory Elements, Transcriptional, High-Throughput Nucleotide Sequencing, Cloning, Molecular, Polymorphism, Single Nucleotide, Genome, Human, Regulatory Elements, Transcriptional
Abstract

The majority of common variants associated with common diseases, as well as an unknown proportion of causal mutations for rare diseases, fall in noncoding regions of the genome. Although catalogs of noncoding regulatory elements are steadily improving, we have a limited understanding of the functional effects of mutations within them. Here, we perform saturation mutagenesis in conjunction with massively parallel reporter assays on 20 disease-associated gene promoters and enhancers, generating functional measurements for over 30,000 single nucleotide substitutions and deletions. We find that the density of putative transcription factor binding sites varies widely between regulatory elements, as does the extent to which evolutionary conservation or integrative scores predict functional effects. These data provide a powerful resource for interpreting the pathogenicity of clinically observed mutations in these disease-associated regulatory elements, and comprise a rich dataset for the further development of algorithms that aim to predict the regulatory effects of noncoding mutations.

Published
2019

35. Communication interventions to promote the public's awareness of antibiotics: a systematic review.

Author

Burstein, Valerie R, Trajano, Renee P, Kravitz, Richard L, Bell, Robert A, Vora, Darshan, and May, Larissa S

Subjects
Humans, Respiratory Tract Infections, Anti-Bacterial Agents, Health Knowledge, Attitudes, Practice, Communication, Drug Resistance, Microbial, Health Promotion, Prescription Drug Overuse, Antibiotics, Messaging programs, Public awareness, Health Knowledge, Attitudes, Practice, Drug Resistance, Microbial, Public Health and Health Services, Public Health
Abstract

BackgroundInappropriate antibiotic use is implicated in antibiotic resistance and resultant morbidity and mortality. Overuse is particularly prevalent for outpatient respiratory infections, and perceived patient expectations likely contribute. Thus, various educational programs have been implemented to educate the public.MethodsWe systematically identified public-directed interventions to promote antibiotic awareness in the United States. PubMed, Google Scholar, Embase, CINAHL, and Scopus were queried for articles published from January 1996 through January 2016. Two investigators independently assessed titles and abstracts of retrieved articles for subsequent full-text review. References of selected articles and three review articles were likewise screened for inclusion. Identified educational interventions were coded for target audience, content, distribution site, communication method, and major outcomes.ResultsOur search yielded 1,106 articles; 34 met inclusion criteria. Due to overlap in interventions studied, 29 distinct educational interventions were identified. Messages were primarily delivered in outpatient clinics (N = 24, 83%) and community sites (N = 12, 41%). The majority included clinician education. Antibiotic prescription rates were assessed for 22 interventions (76%). Patient knowledge, attitudes, and beliefs (KAB) were assessed for 10 interventions (34%). Similar rates of success between antibiotic prescription rates and patient KAB were reported (73 and 70%, respectively). Patient interventions that did not include clinician education were successful to increase KAB but were not shown to decrease antibiotic prescribing. Three interventions targeted reductions in Streptococcus pneumoniae resistance; none were successful.ConclusionsMessaging programs varied in their designs, and many were multifaceted in their approach. These interventions can change patient perspectives regarding antibiotic use, though it is unclear if clinician education is also necessary to reduce antibiotic prescribing. Further investigations are needed to determine the relative influence of interventions focusing on patients and physicians and to determine whether these changes can influence rates of antibiotic resistance long-term.

Published
2019

38. Multi-Trait Genetic Analysis Identifies Autoimmune Loci Associated with Cutaneous Melanoma

Author

Agee, Michelle, Aslibekyan, Stella, Auton, Adam, Babalola, Elizabeth, Bell, Robert K., Bielenberg, Jessica, Bryc, Katarzyna, Bullis, Emily, Cameron, Briana, Coker, Daniella, Cuellar Partida, Gabriel, Dhamija, Devika, Das, Sayantan, Elson, Sarah L., Filshtein, Teresa, Fletez-Brant, Kipper, Fontanillas, Pierre, Freyman, Will, Gandhi, Pooja M., Heilbron, Karl, Hicks, Barry, Hinds, David A., Huber, Karen E., Jewett, Ethan M., Kleinman, Aaron, Kukar, Katelyn, Lin, Keng-Han, Lowe, Maya, Luff, Marie K., McCreight, Jennifer C., McIntyre, Matthew H., McManus, Kimberly F., Micheletti, Steven J., Moreno, Meghan E., Mountain, Joanna L., Mozaffari, Sahar V., Nandakumar, Priyanka, Noblin, Elizabeth S., O'Connell, Jared, Petrakovitz, Aaron A., Poznik, G. David, Shastri, Anjali J., Shelton, Janie F., Shi, Jingchunzi, Shringarpure, Suyash, Tran, Vinh, Tung, Joyce Y., Wang, Xin, Wang, Wei, Weldon, Catherine H., Wilton, Peter, Liyanage, Upekha E., MacGregor, Stuart, Bishop, D. Timothy, Shi, Jianxin, An, Jiyuan, Ong, Jue Sheng, Han, Xikun, Scolyer, Richard A., Martin, Nicholas G., Medland, Sarah E., Byrne, Enda M., Green, Adèle C., Saw, Robyn P.M., Thompson, John F., Stretch, Jonathan, Spillane, Andrew, Jiang, Yunxuan, Tian, Chao, Gordon, Scott G., Duffy, David L., Olsen, Catherine M., Whiteman, David C., Long, Georgina V., Iles, Mark M., Landi, Maria Teresa, and Law, Matthew H.

Published
2022
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40. Prevalence of Alpha-1 Antitrypsin Deficiency, Self-Reported Behavior Change, and Health Care Engagement Among Direct-to-Consumer Recipients of a Personalized Genetic Risk Report

Author

Agee, Michelle, Aslibekyan, Stella, Auton, Adam, Babalola, Elizabeth, Bell, Robert K., Bielenberg, Jessica, Bryc, Katarzyna, Bullis, Emily, Cameron, Briana, Coker, Daniella, Partida, Gabriel Cuellar, Dhamija, Devika, Das, Sayantan, Elson, Sarah L., Filshtein, Teresa, Fletez-Brant, Kipper, Fontanillas, Pierre, Freyman, Will, Gandhi, Pooja M., Heilbron, Karl, Hicks, Barry, Hinds, David A., Huber, Karen E., Jewett, Ethan M., Jiang, Yunxuan, Kleinman, Aaron, Kukar, Katelyn, Lane, Vanessa A., Lin, Keng-Han, Lowe, Maya, Luff, Marie K., McCreight, Jennifer C., McIntyre, Matthew H., McManus, Kimberly F., Micheletti, Steven J., Moreno, Meghan E., Mountain, Joanna L., Mozaffari, Sahar V., Nandakumar, Priyanka, Noblin, Elizabeth S., O’Connell, Jared, Petrakovitz, Aaron A., Poznik, G. David, Schumacher, Morgan, Shastri, Anjali J., Shelton, Janie F., Shi, Jingchunzi, Shringarpure, Suyash, Tian, Chao, Tran, Vinh, Tung, Joyce Y., Wang, Xin, Wang, Wei, Weldon, Catherine H., Wilton, Peter, Ashenhurst, James R., Nhan, Hoang, Wu, Shirley, and Stoller, James K.

Published
2022
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41. Disruption of the β1L Isoform of GABP Reverses Glioblastoma Replicative Immortality in a TERT Promoter Mutation-Dependent Manner

Author

Mancini, Andrew, Xavier-Magalhães, Ana, Woods, Wendy S, Nguyen, Kien-Thiet, Amen, Alexandra M, Hayes, Josie L, Fellmann, Christof, Gapinske, Michael, McKinney, Andrew M, Hong, Chibo, Jones, Lindsey E, Walsh, Kyle M, Bell, Robert JA, Doudna, Jennifer A, Costa, Bruno M, Song, Jun S, Perez-Pinera, Pablo, and Costello, Joseph F

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Biological Sciences, Brain Disorders, Rare Diseases, Cancer, Genetics, Brain Cancer, Animals, Brain Neoplasms, Female, GA-Binding Protein Transcription Factor, Gene Knockdown Techniques, Glioblastoma, Humans, Male, Mice, Mice, Nude, Mutation, Primary Cell Culture, Promoter Regions, Genetic, Protein Isoforms, Protein Multimerization, RNA, Small Interfering, Survival Analysis, Telomerase, Telomere, Tumor Cells, Cultured, Xenograft Model Antitumor Assays, GABP, TERT promoter mutation, cancer immortality, glioblastoma, telomerase, telomeres, Neurosciences, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

TERT promoter mutations reactivate telomerase, allowing for indefinite telomere maintenance and enabling cellular immortalization. These mutations specifically recruit the multimeric ETS factor GABP, which can form two functionally independent transcription factor species: a dimer or a tetramer. We show that genetic disruption of GABPβ1L (β1L), a tetramer-forming isoform of GABP that is dispensable for normal development, results in TERT silencing in a TERT promoter mutation-dependent manner. Reducing TERT expression by disrupting β1L culminates in telomere loss and cell death exclusively in TERT promoter mutant cells. Orthotopic xenografting of β1L-reduced, TERT promoter mutant glioblastoma cells rendered lower tumor burden and longer overall survival in mice. These results highlight the critical role of GABPβ1L in enabling immortality in TERT promoter mutant glioblastoma.

Published
2018

42. Phase 1 and pharmacokinetic study of LY3007113, a p38 MAPK inhibitor, in patients with advanced cancer

Author

Goldman, Jonathan W, Rosen, Lee S, Tolcher, Anthony W, Papadopoulos, Kyriakos, Beeram, Muralidhar, Shi, Peipei, Pitou, Celine, Bell, Robert, Kulanthaivel, Palaniappan, Zhang, Xuekui, Fink, Aaron, Chan, Edward M, Shahir, Ashwin, Farrington, Daphne, and Patnaik, Amita

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Cancer, Patient Safety, Digestive Diseases, Clinical Trials and Supportive Activities, Clinical Research, 6.2 Cellular and gene therapies, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Adult, Aged, Antineoplastic Agents, Biomarkers, Tumor, Dose-Response Relationship, Drug, Female, Humans, Male, Maximum Tolerated Dose, Middle Aged, Neoplasms, Protein Kinase Inhibitors, Treatment Outcome, p38 Mitogen-Activated Protein Kinases, p38 mitogen-activated protein kinase, Advanced cancer, Inhibitor, Pharmacology and Pharmaceutical Sciences, Oncology & Carcinogenesis, Oncology and carcinogenesis, Pharmacology and pharmaceutical sciences
Abstract

Background The signaling protein p38 mitogen-activated protein kinase (MAPK) regulates the tumor cell microenvironment, modulating cell survival, migration, and invasion. This phase 1 study evaluated the safety of p38 MAPK inhibitor LY3007113 in patients with advanced cancer to establish a recommended phase 2 dose. Methods In part A (dose escalation), LY3007113 was administered orally every 12 h (Q12H) at doses ranging from 20 mg to 200 mg daily on a 28-day cycle until the maximum tolerated dose (MTD) was reached. In part B (dose confirmation), patients received MTD. Safety, pharmacokinetics, pharmacodynamics, and tumor response data were evaluated. Results MTD was 30 mg Q12H. The most frequent treatment-related adverse events (>10%) were tremor, rash, stomatitis, increased blood creatine phosphokinase, and fatigue. Grade ≥ 3 treatment-related adverse events included upper gastrointestinal haemorrhage and increased hepatic enzyme, both occurring at 40 mg Q12H and considered dose-limiting toxicities. LY3007113 exhibited an approximately dose-proportional increase in exposure and time-independent pharmacokinetics after repeated dosing. Maximal inhibition (80%) of primary biomarker MAPK-activated protein kinase 2 in peripheral blood mononuclear cells was not reached, and sustained minimal inhibition (60%) was not maintained for 6 h after dosing to achieve a biologically effective dose (BED). The best overall response in part B was stable disease in 3 of 27 patients. Conclusions The recommended phase 2 dosage of LY3007113 was 30 mg Q12H. Three patients continued treatment after the first radiographic assessment, and the BED was not achieved. Further clinical development of this compound is not planned as toxicity precluded achieving a biologically effective dose.

Published
2018

43. Communication about chronic pain and opioids in primary care

Author

Henry, Stephen G, Bell, Robert A, Fenton, Joshua J, and Kravitz, Richard L

Subjects
Biomedical and Clinical Sciences, Health Services and Systems, Clinical Sciences, Health Sciences, Pharmacology and Pharmaceutical Sciences, Chronic Pain, Pain Research, Complementary and Integrative Health, Clinical Research, Health and social care services research, Management of diseases and conditions, 7.1 Individual care needs, 8.1 Organisation and delivery of services, 7.3 Management and decision making, Musculoskeletal, Adult, Aged, Analgesics, Opioid, Communication, Female, Humans, Male, Middle Aged, Pain Management, Pain Measurement, Patient Satisfaction, Physician-Patient Relations, Physicians, Primary Health Care, Surveys and Questionnaires, Opioid analgesics, Chronic pain, Patient-physician relations, Primary care, Patient satisfaction, Medical and Health Sciences, Psychology and Cognitive Sciences, Anesthesiology, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

Patients and physicians report that communication about chronic pain and opioids is often challenging, but there is little empirical research on whether patient-physician communication about pain affects patient and physician visit experience. This study video recorded 86 primary care visits involving 49 physicians and 86 patients taking long-term opioids for chronic musculoskeletal pain, systematically coded all pain-related utterances during these visits using a custom-designed coding system, and administered previsit and postvisit questionnaires. Multiple regression was used to identify communication behaviors and patient characteristics associated with patients' ratings of their visit experience, physicians' ratings of visit difficulty, or both. After adjusting for covariates, 2 communication variables-patient-physician disagreement and patient requests for opioid dose increases-were each significantly associated with both worse ratings of patient experience and greater physician-reported visit difficulty. Patient desire for increased pain medicine was also significantly positively associated with both worse ratings of patient experience and greater physician-reported visit difficulty. Greater pain severity and more patient questions were each significantly associated with greater physician-reported visit difficulty, but not with patient experience. The association between patient requests for opioids and patient experience ratings was wholly driven by 2 visits involving intense conflict with patients demanding opioids. Patient-physician communication during visits is associated with patient and physician ratings of visit experience. Training programs focused on imparting communication skills that assist physicians in negotiating disagreements about pain management, including responding to patient requests for more opioids, likely have potential to improve visit experience ratings for both patients and physicians.

Published
2018

46. MUSSEL: Enhanced Bayesian polygenic risk prediction leveraging information across multiple ancestry groups

Author

Jin, Jin, primary, Zhan, Jianan, additional, Zhang, Jingning, additional, Zhao, Ruzhang, additional, O’Connell, Jared, additional, Jiang, Yunxuan, additional, Aslibekyan, Stella, additional, Auton, Adam, additional, Babalola, Elizabeth, additional, Bell, Robert K., additional, Bielenberg, Jessica, additional, Bryc, Katarzyna, additional, Bullis, Emily, additional, Coker, Daniella, additional, Cuellar Partida, Gabriel, additional, Dhamija, Devika, additional, Das, Sayantan, additional, Elson, Sarah L., additional, Eriksson, Nicholas, additional, Filshtein, Teresa, additional, Fitch, Alison, additional, Fletez-Brant, Kipper, additional, Fontanillas, Pierre, additional, Freyman, Will, additional, Granka, Julie M., additional, Heilbron, Karl, additional, Hernandez, Alejandro, additional, Hicks, Barry, additional, Hinds, David A., additional, Jewett, Ethan M., additional, Kukar, Katelyn, additional, Kwong, Alan, additional, Lin, Keng-Han, additional, Llamas, Bianca A., additional, Lowe, Maya, additional, McCreight, Jey C., additional, McIntyre, Matthew H., additional, Micheletti, Steven J., additional, Moreno, Meghan E., additional, Nandakumar, Priyanka, additional, Nguyen, Dominique T., additional, Noblin, Elizabeth S., additional, Petrakovitz, Aaron A., additional, Poznik, G. David, additional, Reynoso, Alexandra, additional, Schumacher, Morgan, additional, Shastri, Anjali J., additional, Shelton, Janie F., additional, Shi, Jingchunzi, additional, Shringarpure, Suyash, additional, Su, Qiaojuan Jane, additional, Tat, Susana A., additional, Tchakouté, Christophe Toukam, additional, Tran, Vinh, additional, Tung, Joyce Y., additional, Wang, Xin, additional, Wang, Wei, additional, Weldon, Catherine H., additional, Wilton, Peter, additional, Wong, Corinna D., additional, Buyske, Steven, additional, Gignoux, Christopher, additional, Haiman, Christopher, additional, Kenny, Eimear E., additional, Kooperberg, Charles, additional, North, Kari, additional, Koelsch, Bertram L., additional, Wojcik, Genevieve, additional, Zhang, Haoyu, additional, and Chatterjee, Nilanjan, additional

Published
2024
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