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1. Cardiovascular Outcomes in GRADE (Glycemia Reduction Approaches in Type 2 Diabetes: A Comparative Effectiveness Study)

Author

Green, Jennifer B., Everett, Brendan M., Ghosh, Alokananda, Younes, Naji, Krause-Steinrauf, Heidi, Barzilay, Joshua, Desouza, Cyrus, Inzucchi, Silvio E., Pokharel, Yashashwi, Schade, David, Scrymgeour, Alexandra, Tan, Meng H., Utzschneider, Kristina M., Mudaliar, Sunder, Crandall, J.P., McKee, M.D., Behringer-Massera, S., Brown-Friday, J., Xhori, E., Ballentine-Cargill, K., Duran, S., Estrella, H., Gonzalez de la Torre, S., Lukin, J., Phillips, L.S., Burgess, E., Olson, D., Rhee, M., Wilson, P., Raines, T.S., Boers, J., Costello, J., Maher-Albertelli, M., Mungara, R., Savoye, L., White, C.A., Gullett, C., Holloway, L., Morehead, F., Person, S., Sibymon, M., Tanukonda, S., Adams, C., Ross, A., Balasubramanyam, A., Gaba, R., Gonzalez Hattery, E., Ideozu, A., Jimenez, J., Montes, G., Wright, C., Hollander, P., Roe, E., Jackson, A., Smiley, A., Burt, P., Estrada, L., Chionh, K., Ismail-Beigi, F., Falck-Ytter, C., Sayyed Kassem, L., Sood, A., Tiktin, M., Kulow, T., Newman, C., Stancil, K.A., Cramer, B., Iacoboni, J., Kononets, M.V., Sanders, C., Tucker, L., Werner, A., Maxwell, A., McPhee, G., Patel, C., Colosimo, L., Krol, A., Goland, R., Pring, J., Alfano, L., Kringas, P., Hausheer, C., Tejada, J., Gumpel, K., Kirpitch, A., Schneier, H., AbouAssi, H., Chatterjee, R., Feinglos, M.N., English Jones, J., Khan, S.A., Kimpel, J.B., Zimmer, R.P., Furst, M., Satterwhite, B.M., Thacker, C.R., Evans Kreider, K., Mariash, C.N., Mather, K.J., Ismail, H.M., Lteif, A., Mullen, M., Hamilton, T., Patel, N., Riera, G., Jackson, M., Pirics, V., Aguillar, D., Howard, D., Hurt, S., Bergenstal, R., Carlson, A., Martens, T., Johnson, M., Hill, R., Hyatt, J., Jensen, C., Madden, M., Martin, D., Willis, H., Konerza, W., Yang, S., Kleeberger, K., Passi, R., Fortmann, S., Herson, M., Mularski, K., Glauber, H., Prihoda, J., Ash, B., Carlson, C., Ramey, P.A., Schield, E., Torgrimson-Ojerio, B., Arnold, K., Kauffman, B., Panos, E., Sahnow, S., Bays, K., Berame, K., Cook, J., Ghioni, D., Gluth, J., Schell, K., Criscola, J., Friason, C., Jones, S., Nazarov, S., Rassouli, N., Puttnam, R., Ojoawo, B., Nelson, R., Curtis, M., Hollis, B., Sanders-Jones, C., Stokes, K., El-Haqq, Z., Kolli, A., Tran, T., Wexler, D., Larkin, M.E., Meigs, J., Chambers, B., Dushkin, A., Rocchio, G., Yepes, M., Steiner, B., Dulin, H., Cayford, M., Chu, K., DeManbey, A., Hillard, M., Martin, K., Thangthaeng, N., Gurry, L., Kochis, R., Raymond, E., Ripley, V., Stevens, C., Park, J., Aroda, V., Ghazi, A., Magee, M., Ressing, A., Loveland, A., Hamm, M., Hurtado, M., Kuhn, A., Leger, J., Manandhar, L., Mwicigi, F., Sanchez, O., Young, T., Garg, R., Lagari-Libhaber, V., Florez, H.J., Valencia, W.M., Marks, J., Casula, S., Oropesa-Gonzalez, L., Hue, L., Cuadot, A., Nieto-Martinez, R., Riccio Veliz, A.K., Gutt, M., Kendal, Y.J., Veciana, B., Ahmann, A., Aby-Daniel, D., Joarder, F., Morimoto, V., Sprague, C., Yamashita, D., Cady, N., Rivera-Eschright, N., Kirchhoff, P., Morales Gomez, B., Adducci, J., Goncharova, A., Hox, S.H., Petrovitch, H., Matwichyna, M., Jenkins, V., Broadwater, L., Ishii, R.R., Bermudez, N.O., Hsia, D.S., Cefalu, W.T., Greenway, F.L., Waguespack, C., King, E., Fry, G., Dragg, A., Gildersleeve, B., Arceneaux, J., Haynes, N., Thomassie, A., Pavlionis, M., Bourgeois, B., Hazlett, C., Henry, R., Boeder, S., Pettus, J., Diaz, E., Garcia-Acosta, D., Maggs, S., DeLue, C., Stallings, A., Castro, E., Hernandez, S., Krakoff, J., Curtis, J.M., Killean, T., Khalid, M., Joshevama, E., Diaz, E., Martin, D., Tsingine, K., Karshner, T., Albu, J., Pi-Sunyer, F.X., Frances, S., Maggio, C., Ellis, E., Bastawrose, J., Gong, X., Banerji, M.A., August, P., Lee, M., Lorber, D., Brown, N.M., Josephson, D.H., Thomas, L.L., Tsovian, M., Cherian, A., Jacobson, M.H., Mishko, M.M., Kirkman, M.S., Buse, J.B., Diner, J., Dostou, J., Machineni, S., Young, L., Bergamo, K., Goley, A., Kerr, J., Largay, J.F., Guarda, S., Cuffee, J., Culmer, D., Fraser, R., Almeida, H., Coffer, S., Debnam, E., Kiker, L., Morton, S., Josey, K., Fuller, G., Garvey, W.T., Cherrington, A.L., Dyer, D., Lawson, M.C.R., Griffith, O., Agne, A., McCullars, S., Cohen, R.M., Craig, J., Rogge, M.C., Burton, K., Kersey, K., Wilson, C., Lipp, S., Vonder Meulen, M.B., Adkins, C., Onadeko, T., Rasouli, N., Baker, C., Schroeder, E., Razzaghi, M., Lyon, C., Penaloza, R., Underkofler, C., Lorch, R., Douglass, S., Steiner, S., Sivitz, W.I., Cline, E., Knosp, L.K., McConnell, J., Lowe, T., Herman, W.H., Pop-Busui, R., Martin, C., Waltje, A., Katona, A., Goodhall, L., Eggleston, R., Kuo, S., Bojescu, S., Bule, S., Kessler, N., LaSalle, E., Whitley, K., Seaquist, E.R., Bantle, A., Harindhanavudhi, T., Kumar, A., Redmon, B., Bantle, J., Coe, M., Mech, M., Taddese, A., Lesne, L., Smith, S., Kuechenmeister, L., Shivaswamy, V., Burbach, S., Rodriguez, M.G., Seipel, K., Alfred, A., Morales, A.L., Eggert, J., Lord, G., Taylor, W., Tillson, R., Adolphe, A., Burge, M., Duran-Valdez, E., Martinez, J., Bancroft, A., Kunkel, S., Ali Jamaleddin Ahmad, F., Hernandez McGinnis, D., Pucchetti, B., Scripsick, E., Zamorano, A., DeFronzo, R.A., Cersosimo, E., Abdul-Ghani, M., Triplitt, C., Juarez, D., Mullen, M., Garza, R.I., Verastiqui, H., Wright, K., Puckett, C., Raskin, P., Rhee, C., Abraham, S., Jordan, L.F., Sao, S., Morton, L., Smith, O., Osornio Walker, L., Schnurr-Breen, L., Ayala, R., Kreymer, R.B., Sturgess, D., Kahn, S.E., Alarcon-Casas Wright, L., Boyko, E.J., Tsai, E.C., Trence, D.L., Trikudanathan, S., Fattaleh, B.N., Montgomery, B.K., Atkinson, K.M., Kozedub, A., Concepcion, T., Moak, C., Prikhodko, N., Rhothisen, S., Elasy, T.A., Martin, S., Shackelford, L., Goidel, R., Hinkle, N., Lovell, C., Myers, J., Lipps Hogan, J., McGill, J.B., Salam, M., Schweiger, T., Kissel, S., Recklein, C., Clifton, M.J., Tamborlane, W., Camp, A., Gulanski, B., Pham, K., Alguard, M., Gatcomb, P., Lessard, K., Perez, M., Iannone, L., Magenheimer, E., Montosa, A., Cefalu, W.T., Fradkin, J., Burch, H.B., Bremer, A.A., Nathan, D.M., Lachin, J.M., Buse, J.B., Kahn, S.E., Larkin, M.E., Tiktin, M., Wexler, D., Burch, H.B., Bremer, A.A., Lachin, J.M., Bebu, I., Butera, N., Buys, C.J., Fagan, A., Gao, Y., Gramzinski, M.R., Hall, S.D., Kazemi, E., Legowski, E., Liu, H., Suratt, C., Tripputi, M., Arey, A., Backman, M., Bethepu, J., Lund, C., Mangat Dhaliwal, P., McGee, P., Mesimer, E., Ngo, L., Steffes, M., Seegmiller, J., Saenger, A., Arends, V., Gabrielson, D., Conner, T., Warren, S., Day, J., Huminik, J., Soliman, E.Z., Zhang, Z.M., Campbell, C., Hu, J., Keasler, L., Hensley, S., Li, Y., Herman, W.H., Kuo, S., Martin, C., Waltje, A., Mihalcea, R., Min, D.J., Perez-Rosas, V., Prosser, L., Resnicow, K., Ye, W., Shao, H., Zhang, P., Luchsinger, J., Sanchez, D., Assuras, S., Groessl, E., Sakha, F., Chong, H., Hillery, N., Abdouch, I., Bahtiyar, G., Brantley, P., Broyles, F.E., Canaris, G., Copeland, P., Craine, J.J., Fein, W.L., Gliwa, A., Hope, L., Lee, M.S., Meiners, R., Meiners, V., O’Neal, H., Park, J.E., Sacerdote, A., Sledge Jr, E., Soni, L., Steppel-Reznik, J., and Turchin, A.

Published
2024
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2. Reversible and non-reversible Markov Chain Monte Carlo algorithms for reservoir simulation problems

Author

Dobson, P., Fursov, I., Lord, G., and Ottobre, M.

Subjects
Statistics - Applications
Abstract

We compare numerically the performance of reversible and non-reversible Markov Chain Monte Carlo algorithms for high dimensional oil reservoir problems; because of the nature of the problem at hand, the target measures from which we sample are supported on bounded domains. We compare two strategies to deal with bounded domains, namely reflecting proposals off the boundary and rejecting them when they fall outside of the domain. We observe that for complex high dimensional problems reflection mechanisms outperform rejection approaches and that the advantage of introducing non-reversibility in the Markov Chain employed for sampling is more and more visible as the dimension of the parameter space increases.

Published
2019

4. P999 First in human treatment of Crohn’s disease with autologous ex-vivo expanded polyclonal, gut-targeted regulatory T cells: Initial results of the TRIBUTE feasibility study

Author

Irving, P M, primary, Seah, D, additional, Centritto, A, additional, Clough, J, additional, Canavan, J, additional, Goldberg, R, additional, Prevost, A T, additional, Vasconcelos, J C, additional, Lyne, M, additional, Palmer Joyce, J, additional, Patel, P, additional, Tasker, S, additional, Marks, P, additional, Rodger, B, additional, Jackson, I, additional, Macallan, D, additional, Ong, M, additional, Sutcliffe, M, additional, Travis, M, additional, and Lord, G, additional

Published
2024
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7. Freezing Stochastic Travelling Waves

Author

Lord, G. J. and Thuemmler, V.

Subjects
Mathematics - Numerical Analysis, Nonlinear Sciences - Pattern Formation and Solitons
Abstract

We consider in this paper travelling wave solutions to stochastic partial differential equations and corresponding wave speed. As a particular example we consider the Nagumo equation with multiplicative noise which we mainly consider in the Stratonovich sense. A standard approach to determine the position and hence speed of a wave is to compute the evolution of a level set. We compare this approach against an alternative where the wave position is found by minimizing the $L^2$ norm against a fixed profile. This approach can also be used to stop (or freeze) the wave and obtain a stochastic partial differential algebraic equation that we then discretize and solve. Although attractive as it leads to a smaller domain size it can be numerically unstable due to large convection terms. We compare numerically the different approaches for estimating the wave speed. Minimization against a fixed profile works well provided the support of the reference function is not too narrow. We then use these techniques to investigate the effect of both \Ito and Stratonovich noise on the Nagumo equation as correlation length and noise intensity increases.

Published
2010

8. Finite to infinite steady state solutions, bifurcations of an integro-differential equation

Author

Bhowmik, S. K., Duncan, D. B., Grinfeld, M., and Lord, G. J.

Subjects
Mathematics - Dynamical Systems
Abstract

We consider a bistable integral equation which governs the stationary solutions of a convolution model of solid--solid phase transitions on a circle. We study the bifurcations of the set of the stationary solutions as the diffusion coefficient is varied to examine the transition from an infinite number of steady states to three for the continuum limit of the semi--discretised system. We show how the symmetry of the problem is responsible for the generation and stabilisation of equilibria and comment on the puzzling connection between continuity and stability that exists in this problem.

Published
2010

9. Bifurcations in the regularized Ericksen bar model

Author

Grinfeld, M. and Lord, G. J.

Subjects
Mathematics - Dynamical Systems
Abstract

We consider the regularized Ericksen model of an elastic bar on an elastic foundation on an interval with Dirichlet boundary conditions as a two-parameter bifurcation problem. We explore, using local bifurcation analysis and continuation methods, the structure of bifurcations from double zero eigenvalues. Our results provide evidence in support of M\"uller's conjecture \cite{Muller} concerning the symmetry of local minimizers of the associated energy functional and describe in detail the structure of the primary branch connections that occur in this problem. We give a reformulation of M\"uller's conjecture and suggest two further conjectures based on the local analysis and numerical observations. We conclude by analysing a ``loop'' structure that characterizes $(k,3k)$ bifurcations.

Published
2007

17. Clinical and Metabolic Characterization of Adults With Type 2 Diabetes by Age in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) Cohort

Author

Aroda, Vanita R., Krause-Steinrauf, Heidi, Kazemi, Erin J., Buse, John B., Gulanski, Barbara I., Florez, Hermes J., Ahmann, Andrew J., Loveland, Amy, Kuhn, Alexander, Lonier, Jacqueline Y., Wexler, Deborah J., Crandall, J.P., McKee, M.D., Behringer-Massera, S., Brown-Friday, J., Xhori, E., Ballentine-Cargill, K., Duran, S., Estrella, H., Gonzalez de la torre, S., Lukin, J., Phillips, L.S., Burgess, E., Olson, D., Rhee, M., Wilson, P., Raines, T.S., Boers, J., Costello, J., Maher-Albertelli, M., Mungara, R., Savoye, L., White, C.A., Gullett, C., Holloway, L., Morehead, F., Person, S., Sibymon, M., Tanukonda, S., Adams, C., Ross, A., Balasubramanyam, A., Gaba, R., Gonzalez Hattery, E., Ideozu, A., Jimenez, J., Montes, G., Wright, C., Hollander, P., Roe, E., Jackson, A., Smiley, A., Burt, P., Estrada, L., Chionh, K., Ismail-Beigi, F., Falck-Ytter, C., Sayyed Kassem, L., Sood, A., Tiktin, M., Kulow, T., Newman, C., Stancil, K.A., Cramer, B., Iacoboni, J., Kononets, M.V., Sanders, C., Tucker, L., Werner, A., Maxwell, A., McPhee, G., Patel, C., Colosimo, L., Krol, A., Goland, R., Pring, J., Alfano, L., Kringas, P., Hausheer, C., Tejada, J., Gumpel, K., Kirpitch, A., Schneier, H., Green, J.B., AbouAssi, H., Chatterjee, R., Feinglos, M.N., English Jones, J., Khan, S.A., Kimpel, J.B., Zimmer, R.P., Furst, M., Satterwhite, B.M., Thacker, C.R., Evans Kreider, K., Mariash, C.N., Mather, K.J., Ismail, H.M., Lteif, A., Mullen, M., Hamilton, T., Patel, N., Riera, G., Jackson, M., Pirics, V., Aguillar, D., Howard, D., Hurt, S., Bergenstal, R., Carlson, A., Martens, T., Johnson, M., Hill, R., Hyatt, J., Jensen, C., Madden, M., Martin, D., Willis, H., Konerza, W., Yang, S., Kleeberger, K., Passi, R., Fortmann, S., Herson, M., Mularski, K., Glauber, H., Prihoda, J., Ash, B., Carlson, C., Ramey, P.A., Schield, E., Torgrimson-Ojerio, B., Arnold, K., Kauffman, B., Panos, E., Sahnow, S., Bays, K., Berame, K., Cook, J., Ghioni, D., Gluth, J., Schell, K., Criscola, J., Friason, C., Jones, S., Nazarov, S., Barzilay, J., Rassouli, N., Puttnam, R., Ojoawo, B., Nelson, R., Curtis, M., Hollis, B., Sanders-Jones, C., Stokes, K., El-Haqq, Z., Kolli, A., Tran, T., Wexler, D., Larkin, M., Meigs, J., Chambers, B., Dushkin, A., Rocchio, G., Yepes, M., Steiner, B., Dulin, H., Cayford, M., Chu, K., DeManbey, A., Hillard, M., Martin, K., Thangthaeng, N., Gurry, L., Kochis, R., Raymond, E., Ripley, V., Stevens, C., Park, J., Aroda, V., Ghazi, A., Magee, M., Ressing, Ann, Loveland, A., Hamm, M., Hurtado, M., Kuhn, A., Leger, J., Manandhar, L., Sanchez, O., Young, T., Mofor, F., Garg, R., Lagari-Libhaber, V., Florez, H.J., Valencia, W.M., Marks, J., Casula, S., Oropesa-Gonzalez, L., Hue, L., Cuadot, A., Nieto-Martinez, R., Riccio Veliz, A.K., Gutt, M., Kendal, Y.J., Veciana, B., Ahmann, A., Aby-Daniel, D., Joarder, F., Morimoto, V., Sprague, C., Yamashita, D., Cady, N., Rivera-Eschright, N., Kirchhoff, P., Morales Gomez, B., Adducci, J., Goncharova, A., Hox, S.H., Petrovitch, H., Matwichyna, M., Jenkins, V., Broadwater, L., Ishii, R.R., Bermudez, N.O., Hsia, D.S., Cefalu, W.T., Greenway, F.L., Waguespack, C., King, E., Fry, G., Dragg, A., Gildersleeve, B., Arceneaux, J., Haynes, N., Thomassie, A., Pavlionis, M., Bourgeois, B., Hazlett, C., Mudaliar, S., Henry, R., Boeder, S., Pettus, J., Diaz, E., Garcia-Acosta, D., Maggs, S., DeLue, C., Stallings, A., Castro, E., Hernandez, S., Krakoff, J., Curtis, J.M., Killean, T., Khalid, M., Joshevama, E., Tsingine, K., Karshner, T., Albu, J., Pi-Sunyer, F.X., Frances, S., Maggio, C., Ellis, E., Bastawrose, J., Gong, X., Banerji, M.A., August, P., Lee, M., Lorber, D., Brown, N.M., Josephson, D.H., Thomas, L.L., Tsovian, M., Cherian, A., Jacobson, M.H., Mishko, M.M., Kirkman, M.S., Buse, J.B., Dostou, J., Machineni, S., Young, L., Bergamo, K., Goley, A., Kerr, J., Largay, J.F., Guarda, S., Cuffee, J., Culmer, D., Fraser, R., Almeida, H., Coffer, S., Debnam, E., Kiker, L., Morton, S., Josey, K., Fuller, G., Garvey, W.T., Cherrington, A.L., Dyer, D., Lawson, M.C.R., Griffith, O., Agne, A., McCullars, S., Cohen, R.M., Craig, J., Rogge, M.C., Burton, K., Kersey, K., Wilson, C., Lipp, S., Vonder Meulen, M.B., Adkins, C., Onadeko, T., Rasouli, N., Baker, C., Schroeder, E., Razzaghi, M., Lyon, C., Penaloza, R., Underkofler, C., Lorch, R., Douglass, S., Steiner, S., Sivitz, W.I., Cline, E., Knosp, L.K., McConnell, J., Lowe, T., Herman, W.H., Pop-Busui, R., Tan, M.H., Martin, C., Waltje, A., Katona, A., Goodhall, L., Eggleston, R., Kuo, S., Bojescu, S., Bule, S., Kessler, N., LaSalle, E., Whitley, K., Seaquist, E.R., Bantle, A., Harindhanavudhi, T., Kumar, A., Redmon, B., Bantle, J., Coe, M., Mech, M., Taddese, A., Lesne, L., Smith, S., Desouza, C., Kuechenmeister, L., Shivaswamy, V., Burbach, S., Rodriguez, M.G., Seipel, K., Alfred, A., Morales, A.L., Eggert, J., Lord, G., Taylor, W., Tillson, R., Schade, D.S., Adolphe, A., Burge, M., Duran-Valdez, E., Martinez, J., Bancroft, A., Kunkel, S., Ali Jamaleddin Ahmad, F., Hernandez McGinnis, D., Pucchetti, B., Scripsick, E., Zamorano, A., DeFronzo, R.A., Cersosimo, E., Abdul-Ghani, M., Triplitt, C., Juarez, D., Garza, R.I., Verastiqui, H., Wright, K., Puckett, C., Raskin, P., Rhee, C., Abraham, S., Jordan, L.F., Sao, S., Morton, L., Smith, O., Osornio Walker, L., Schnurr-Breen, L., Ayala, R., Kreymer, R.B., Sturgess, D., Utzschneider, K.M., Kahn, S.E., Alarcon-Casas, L., Wright, L., Boyko, E.J., Tsai, E.C., Trence, D.L., Trikudanathan, S., Fattaleh, B.N., Montgomery, B.K., Atkinson, K.M., Kozedub, A., Concepcion, T., Moak, C., Prikhodko, N., Rhothisen, S., Elasy, T.A., Martin, S., Shackelford, L., Goidel, R., Hinkle, N., Lovell, C., Myers, J., Lipps Hogan, J., McGill, J.B., Salam, M., Schweiger, T., Kissel, S., Recklein, C., Clifton, M.J., Tamborlane, W., Camp, A., Gulanski, B., Inzucchi, S.E., Pham, K., Alguard, M., Gatcomb, P., Lessard, K., Perez, M., Iannone, L., Magenheimer, E., Montosa, A., Burch, H.B., Bremer, A.A., Fradkin, J., Nathan, D.M., Lachin, J.M., Krause-Steinrauf, H., Younes, N., Backman, M., Bebu, I., Butera, N., Buys, C.J., Fagan Murphy, A., Gao, Y., Ghosh, A., Gramzinski, M.R., Kazemi, E., Hall, S.D., Legowski, E., Suratt, C., Tripputi, M., Arey, A., Bethepu, J., Lund, C., Mangat Dhaliwal, P., McGee, P., Mesimer, E., Ngo, L., Steffes, M., Seegmiller, J., Saenger, A., Arends, V., Gabrielson, D., Conner, T., Warren, S., Day, J., Huminik, J., Scrymgeour, A., Soliman, E.Z., Pokharel, Y., Zhang, Z.M., Campbell, C., Hu, J., Keasler, L., Hensley, S., Li, Y., Mihalcea, R., Min, D.J., Perez-Rosas, V., Prosser, L., Resnicow, K., Ye, W., Shao, H., Zhang, P., Luchsinger, J., Sanchez, D., Assuras, S., Groessl, E., Sakha, F., Chong, H., Hillery, N., Everett, B.M., Abdouch, I., Bahtiyar, G., Brantley, P., Broyles, F.E., Canaris, G., Copeland, P., Craine, J.J., Fein, W.L., Gliwa, A., Hope, L., Lee, M.S., Meiners, R., Meiners, V., O’Neal, H., Park, J.E., Sacerdote, A., Sledge, E., Soni, L., Steppel-Reznik, J., Turchin, A., Brooks-Worrell, B., Hampe, C.S., Newgard, C.B., Palmer, J.P., Shojaie, A., Higgins, J., Fischer, L., Golden, S., Gonzalez, J., Naik, A., Walker, E., Doner Lotenberg, L., Gallivan, J.M., Lim, J., and Tuncer, D.M.

Subjects
Clinical Care/Education/Nutrition/Psychosocial Research
Abstract

OBJECTIVE: Differences in type 2 diabetes phenotype by age are described, but it is not known whether these differences are seen in a more uniformly defined adult population at a common early stage of care. We sought to characterize age-related clinical and metabolic characteristics of adults with type 2 diabetes on metformin monotherapy, prior to treatment intensification. RESEARCH DESIGN AND METHODS: In the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE), participants were enrolled who had type 2 diabetes duration

Published
2022

20. Immune checkpoint inhibitor-induced colitis is mediated by polyfunctional lymphocytes and is dependent on the IL23/IFNg axis

Author

Lo, J, Cozzetto, D, Madgwick, M, Sieh, JYXS, Olbei, M, Alexander, JL, Blanco, JM, Kudo, H, Ibraheim, H, Liu, Z, Seoane, RC, Goldin, R, Marchesi, J, Korcsmaros, T, Lord, G, and Powell, N

Abstract

Immune checkpoint inhibitors (CPIs) have revolutionised cancer treatment, with previously untreatable disease now amenable to potential cure. Combination regimens of anti-CTLA-4 and anti-PD-1 show enhanced efficacy but are prone to off-target immune-mediated tissue injury, particularly at the barrier surfaces. CPI-induced colitis is a common and serious complication. To probe the impact of immune checkpoints on intestinal homeostasis, mice were challenged with combination anti-CTLA-4/anti-PD-1 immunotherapy and manipulation of the intestinal microbiota. Colonic immune responses were profiled using bulk and single-cell RNA-sequencing and flow cytometry. CPI-colitis was dependent on the composition of the intestinal microbiota and was characterized by remodelling of mucosal lymphocytes with induction of polyfunctional lymphocyte responses characterized by increased expression of interferon-γ (IFNγ), other pro-inflammatory cytokines/chemokines (Il22, Il17a Ccl3, Ccl4 and Ccl9), cytotoxicity molecules (Gzmb, Gzma, Prf1, Nkg7) and the chemokine receptor Cxcr6. In comparison with mucosal lymphocytes in the steady state, polyfunctional lymphocytes from both CD4+ and CD8+ lineages upregulated costimulatory molecules and checkpoint molecules in CPI-colitis, indicating that these cells are tightly regulated. CPI-colitis was attenuated following depletion of effector lymphocytes or following blockade of the IL23/IFNγ axis. This study provides new mechanistic insights into CPI-colitis, identifying polyfunctional, cytotoxic lymphocytes as key mediators of disease. Therapeutic targeting of their effector response or regulatory networks, including the IL23/IFNγ axis likely holds the key to preventing and reversing CPI-colitis.

Published
2022

21. P001 Immune checkpoint inhibitor-induced colitis is mediated by polyfunctional lymphocytes and is dependent on the IL23/IFNg axis

Author

Lo, J, primary, Cozzetto, D, additional, Madgwick, M, additional, Sieh, J Y X S, additional, Olbei, M, additional, Alexander, J L, additional, Miguens Blanco, J, additional, Kudo, H, additional, Ibraheim, H, additional, Liu, Z, additional, Castro Seoane, R, additional, Goldin, R, additional, Marchesi, J, additional, Korcsmaros, T, additional, Lord, G, additional, and Powell, N, additional

Published
2022
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26. The relationship between troponin level and mortality in an unselected population of over 250,000 patients with suspected acute coronary syndrome (NIHR Health Informatics Collaborative Trop-risk study)

Author

Kaura, A, Panoulas, V, Glampson, B, Davies, J, Mulla, A, Woods, K, Omigie, J, Shah, AD, Channon, K, Weber, JN, Thursz, MR, Elliott, P, Hemingway, H, Williams, B, Asselbergs, F, O'Sullivan, M, Lord, G, Melikian, N, Kharbanda, R, Shah, A, Perera, D, Patel, R, Francis, D, and Mayet, J

Published
2021

28. The prognostic implication of a positive troponin across the age spectrum in a quarter of a million patients with suspected acute coronary syndrome (NIHR Health Informatics Collaborative Trop-risk Study)

Author

Kaura, A, Panoulas, V, Glampson, B, Davies, J, Mulla, A, Woods, K, Omigie, J, Shah, AD, Channon, K, Weber, JN, Thursz, MR, Elliott, P, Hemingway, H, Williams, B, Asselbergs, F, O'Sullivan, M, Lord, G, Melikian, N, Kharbanda, R, Shah, A, Perera, D, Patel, R, Francis, D, and Mayet, J

Published
2021

29. The role of high-sensitivity C-reactive protein in predicting mortality beyond troponin in over 100,000 patients with suspected acute coronary syndrome (NIHR Health Informatics Collaborative CRP-risk Study)

Author

Kaura, A, Hartley, A, Panoulas, V, Glampson, B, Davies, J, Mulla, A, Woods, K, Omigie, J, Shah, AD, Channon, K, Weber, JN, Thursz, MR, Elliott, P, Hemingway, H, Williams, B, Asselbergs, F, O'Sullivan, M, Haskard, D, Lord, G, Melikian, N, Francis, D, Koenig, W, Perera, D, Shah, A, Kharbanda, R, Patel, R, Mayet, J, and Khamis, R

Published
2021

36. OP13 Mucosal organoids capture Innate Lymphoid Cells (ILC) tissue-specific development and reveal that Inflammatory Bowel Disease-associated ILC modulate intestinal remodelling

Author

Jowett, G M, primary, Read, E, additional, Norman, M D, additional, Arevalo, P A, additional, Vilà González, M, additional, Roberts, L, additional, Vallier, L, additional, Curtis, M, additional, Lord, G, additional, Gentleman, E, additional, and Neves, J F, additional

Published
2021
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39. Invasive versus non-invasive management of elderly patients with non-ST elevation myocardial infarction: cohort study based on routine clinical data

Author

Kaura, A, Sterne, J, Trickey, A, Abbott, S, Mulla, A, Glampson, B, Panoulas, V, Davies, J, Woods, K, Omigie, J, Shah, A, Channon, K, Weber, J, Thursz, M, Elliott, P, Hemingway, H, Williams, B, Asselbergs, F, O’Sullivan, M, Lord, G, Melikian, N, Johnson, T, Francis, D, Perera, D, Kharbanda, R, Patel, R, Mayet, J, National Institute for Health Research, Imperial College Healthcare NHS Trust- BRC Funding, and British Heart Foundation

Subjects
General & Internal Medicine, 11 Medical and Health Sciences
Abstract

Background Previous trials suggest lower long-term mortality after invasive rather than non-invasive management among patients with non-ST elevation myocardial infarction (NSTEMI), but these excluded very elderly patients. Methods We estimated the effect of invasive versus non-invasive management within 3 days of peak troponin on survival in NSTEMI patients aged ≥80 years, using routine clinical data collected during 2010–2017 (NIHR Health Informatics Collaborative). Propensity scores based on pre-treatment variables were derived using logistic regression; patients with high probabilities of non-invasive or invasive management were excluded. Patients who died within 3 days without receiving invasive management were assigned to the invasive or non-invasive management groups based on their propensity scores, to mitigate immortal time bias. We estimated mortality hazard ratios comparing invasive with non-invasive management, and also compared rates of hospital admission for heart failure. Findings Of 1976 patients with NSTEMI, 101 died within 3 days of their peak troponin, whilst 375 were excluded because of extreme propensity scores. The remaining 1500 patients (56% non-invasive management) had a median age 86 (IQR 82-89) years. During median follow-up of 3.0 (IQR 1.2-4.8) years, there were 613 (41%) deaths. Using inverse probability weighting, adjusted cumulative 5-year mortality was 36% and 55% in the invasive and non-invasive management groups, respectively. The mortality hazard ratio comparing invasive with non-invasive management was 0.64 (95% CI 0.52-0.79) after multivariable adjustment for clinical characteristics and propensity score and inclusion of patients who died within three days. Invasive management was associated with lower incidence of hospital admissions for heart failure (adjusted rate ratio compared with non-invasive management 0.67, 95% CI 0.48–0.93).

Published
2020

40. The early paradoxidid harlani trilobite fauna of Massachusetts and its correlatives in Newfoundland, Morocco, and Spain

Author

Fletcher, Terence P., Theokritoff, George, Lord, G. Stinson, and Zeoli, Gerald

Subjects
Trilobites -- Research, Paleontology -- Research, Biological sciences, Science and technology
Abstract

The Cambrian fauna of Massachusetts, characterized by Paradoxides (Hydrocephalus) harlani, is poorly preserved. Better-preserved specimens, occurring within the stratigraphic range of this trilobite in southeastern Newfoundland and Morocco, provide a better understanding of such taxa to widen the scope of correlation. The paradoxidid-bearing Braintree Formation has revealed three trilobite species to add to those recently recorded. They represent Ellipsocepfialoidea not previously recognized in this Massachusetts sequence, namely Protoleninae by Hamatolenus (H.) aff. H. (H.) marocanus and H. (Myopsolenus) aff. H. (M.) magnus and Ellipsocephalidae by Holocephalina aff. H. levis, thus strengthening faunal relationships with midshelf Cambrian sequences in Morocco and Spain. Reinterpretations of Agnostida, based on Newfoundland material associated with P. (Hydrocephalus) harlani, indicate that Condylopyge eli and Kiskinella cf. K. cristata signify a stratigraphic position for part of the Massachusetts sequence a little above the first appearance of Ovatoryctocara granulata. Appearance of this latter species is under review as the basal boundary of a global Cambrian stage, and is below the sequence break within the Chamberlain's Brook Formation in Newfoundland marked by the Easter Cove Blister Bed. The problem of differentiating species with numerous variable growth stages is highlighted in the ontogenies and stratigraphic ranges of P. (H.) harlani and P. (Plutonides) haywardi and emphasizes the importance of cephalic morphology in paradoxidid classification. Details of the holotypes of Agraulos quadrangularis and Braintreella rogersi and Czech topotypes of Agraulos ceticephalus supplement generic and specific characters poorly understood, especially those involving proportional differences between tectonically/taphonomically flattened examples and undistorted high-relief specimens.

Published
2005

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