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2,729 results on '"Fleming, Thomas"'

1. Monitoring overall survival in pivotal trials in indolent cancers

Author

Fleming, Thomas R, Hampson, Lisa V, Bharani-Dharan, Bharani, Bretz, Frank, Chakravartty, Arunava, Coroller, Thibaud, Koukouli, Evanthia, Wittes, Janet, Yateman, Nigel, and Zuber, Emmanuel

Subjects
Statistics - Applications
Abstract

Indolent cancers are characterized by long overall survival (OS) times. Therefore, powering a clinical trial to provide definitive assessment of the effects of an experimental intervention on OS in a reasonable timeframe is generally infeasible. Instead, the primary outcome in many pivotal trials is an intermediate clinical response such as progression-free survival (PFS). In several recently reported pivotal trials of interventions for indolent cancers that yielded promising results on an intermediate outcome, however, more mature data or post-approval trials showed concerning OS trends. These problematic results have prompted a keen interest in quantitative approaches for monitoring OS that can support regulatory decision-making related to the risk of an unacceptably large detrimental effect on OS. For example, the US Food and Drug Administration, the American Association for Cancer Research, and the American Statistical Association recently organized a one-day multi-stakeholder workshop entitled 'Overall Survival in Oncology Clinical Trials'. In this paper, we propose OS monitoring guidelines tailored for the setting of indolent cancers. Our pragmatic approach is modeled, in part, on the monitoring guidelines the FDA has used in cardiovascular safety trials conducted in Type 2 Diabetes Mellitus. We illustrate proposals through application to several examples informed by actual case studies., Comment: 28 pages, 5 tables

Published
2023

3. The reactive pyruvate metabolite dimethylglyoxal mediates neurological consequences of diabetes

Author

Rhein, Sina, Costalunga, Riccardo, Inderhees, Julica, Gürtzgen, Tammo, Faupel, Teresa Christina, Shaheryar, Zaib, Arrulo Pereira, Adriana, Othman, Alaa, Begemann, Kimberly, Binder, Sonja, Stölting, Ines, Dorta, Valentina, Nawroth, Peter P., Fleming, Thomas, Oexle, Konrad, Prevot, Vincent, Nogueiras, Ruben, Meyhöfer, Svenja, Meyhöfer, Sebastian M., and Schwaninger, Markus

Published
2024
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7. Endothelial Notch1 signaling in white adipose tissue promotes cancer cachexia

Author

Taylor, Jacqueline, Uhl, Leonie, Moll, Iris, Hasan, Sana Safatul, Wiedmann, Lena, Morgenstern, Jakob, Giaimo, Benedetto Daniele, Friedrich, Tobias, Alsina-Sanchis, Elisenda, De Angelis Rigotti, Francesca, Mülfarth, Ronja, Kaltenbach, Sarah, Schenk, Darius, Nickel, Felix, Fleming, Thomas, Sprinzak, David, Mogler, Carolin, Korff, Thomas, Billeter, Adrian T., Müller-Stich, Beat P., Berriel Diaz, Mauricio, Borggrefe, Tilman, Herzig, Stephan, Rohm, Maria, Rodriguez-Vita, Juan, and Fischer, Andreas

Published
2023
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14. FDA/Arthritis Foundation osteoarthritis drug development workshop recap: Assessment of long-term benefit

Author

Kim, Jason S, Borges, Silvana, Clauw, Daniel J, Conaghan, Philip G, Felson, David T, Fleming, Thomas R, Glaser, Rachel, Hart, Elizabeth, Hochberg, Marc, Kim, Yura, Kraus, Virginia B, Lapteva, Larissa, Li, Xiaojuan, Majumdar, Sharmila, McAlindon, Timothy E, Mobasheri, Ali, Neogi, Tuhina, Roemer, Frank W, Rothwell, Rebecca, Shibuya, Robert, Siegel, Jeffrey, Simon, Lee S, Spindler, Kurt P, and Nikolov, Nikolay P

Subjects
Medical Biotechnology, Biomedical and Clinical Sciences, Osteoarthritis, Aging, Arthritis, Clinical Research, Clinical Trials and Supportive Activities, Musculoskeletal, Good Health and Well Being, Biomarkers, Disease Progression, Drug Development, Humans, Structure-modifying therapy, Regulatory approval, Drug development, Disease-modifying therapy, Clinical benefit, Long-term benefit, Clinical Sciences, Public Health and Health Services, Arthritis & Rheumatology, Clinical sciences
Abstract

ObjectiveTo summarize proceedings of a workshop convened to discuss the current state of science in the disease of osteoarthritis (OA), identify the knowledge gaps, and examine the developmental and regulatory challenges in bringing these products to market.DesignSummary of the one-day workshop held virtually on June 22nd, 2021.ResultsSpeakers selected by the Planning Committee presented data on the current approach to assessment of OA therapies, biomarkers in OA drug development, and the assessment of disease progression and long-term benefit.ConclusionsDemonstrated by numerous failed clinical trials, OA is a challenging disease for which to develop therapeutics. The challenge is magnified by the slow time of onset of disease and the need for clinical trials of long duration and/or large sample size to demonstrate the effect of an intervention. The OA science community, including academia, pharmaceutical companies, regulatory agencies, and patient communities, must continue to develop and test better clinical endpoints that meaningfully reflect disease modification related to long-term patient benefit.

Published
2022

16. Dedicated anticoagulation management protocols in fragility femoral fracture care – a source of significant variance and limited effectiveness in improving time to surgery: The hip and femoral fracture anticoagulation surgical timing evaluation (HASTE) study

Author

Smith, Matthew, Yoong, Andrel, Lim, Jun Wei, Yousef, Omar, McDonald, Stephen, Chileshe, Chinga, Ramus, Camilla, Clements, Christopher, Barrett, Liam, Rockall, Oliver, Geetala, Rahul, Islam, Saif Ul, Nasar, Ahmad, Almond, Kieran, Hassan, Ladan Fatima Yusuf, Shah, Sohan, Brand, Robert Bruce, Yawar, Bakhat, Gilmore, Catherine, McAuley, Daryl, Khan, Waleed, Subramanian, Padmanabhan, Ahluwalia, Aashish, Ozbek, Leyla, Awasthi, Prashant, Sheikh, Hassaan, Barkley, Sarah, Ardolino, Toni, Denning, Alexander, Thiruchandran, Gaj, Fraig, Hossam, Salim, Omar, Iqbal, Rabia, Guy, Stephen, Hogg, Jack, Bagshaw, Oliver, Asmar, Samir, Mitchell, Stephen, Quek, Fang, Fletcher, James, French, Jonathan, Graham, Selina, Sloper, Philip, Sadique, Hammad, Matera, Valentina, Sohail, Zain, Leong, Justin Wei, Issa, Fares, Greasley, Lauren, Marsden, Samuel, Parry, Lucy, Mannan, Syed, Zaheen, Humayoon, Moriarty, Peter, Manning, William, Morris, Timothy, Brockbanks, Carole, Ward, Peter, Pearce, Kim, McMenemy, Louise, Mahmoud, Mohamed, Kieffer, Will, Lal, Aayush, Collis, Justin, Chandrasekaran, Karthik, Foxall-Smith, Michael, Raad, Marjan, Kempshall, Peter, Cheuk, Jocelyn, Leckey, Sam, Gupta, Rishav, Engelke, Daniel, Kemp, Mark, Venkatesan, Aakaash, Hussain, Adnan, Simons, Michiel, Raghavendra, Ram Mohan, Rohra, Satish, Deo, Sunny, Vasarhelyi, Ferenc, Thelwall, Claire, Cullen, Krista, Al-Obaidi, Bilal, Fell, Adam, Thaumeen, Ahmad, Dadabhoy, Maria, Ali, Mira, Ijaz, Sameer, Lin, David, Khan, Basharat, Alsonbaty, Mohamed, Lebe, Moritz, Millan, Ravi Kant, Imam, Sam, Theobald, Emma, Cormack, Jonathan, Sharoff, Lokesh, Eardley, Will, Jeyapalan, Rathan, Alcock, Liam, Clayton, Julia, Bates, Natalie, Mahmoud, Yousif, Osborne, Alex, Ralhan, Shvaita, Carpenter, Catriona, Ahmad, Mahmood, Ravi, Sanjeev Musuvathy, Konbaz, Tarek, Lloyd, Thomas, Sheikh, Nomaan, Swealem, Ahmed, Soroya, Emma, Rayan, Faizal, Ward, Thomas, Vasireddy, Aswinkumar, Clarke, Ellisiv, Sikdar, Oishi, Smart, Yat Wing, Windley, Joseph, Ilagan, Belen, Brophy, Edel, Joseph, Sarah, Lowery, Kathryn, Jamjoom, Ammer, Ismayl, Ghiath, Aujla, Randeep, Sambhwani, Sharan, Ramasamy, Arul, Khalaf, Ahmed, Ponugoti, Nikhil, Teng, Wai Huang, Masud, Saqib, Otoibhili, Eghe, Clarkson, Martin, Nafea, Mohamed, Sarhan, Mohamed, Hanna, Shady, Kelly, Andrew, Curtis, Alex, Gourbault, Lysander, Tarhini, Mariam, Platt, Nicholas, Fleming, Thomas, Pemmaraju, Gopalakrishna, Choudri, Mohammed Junaid, Burahee, Abdus, Hassan, Labiba, Hamid, Laveeza, Loveday, David, Edres, Kareem, Schankat, Kerstin, Granger, Luke, Goodbun, Matthew, Parikh, Sunny, Johnson-Lynn, Sarah, Griffiths, Alexandra, Rai, Avinash, Chandler, Henry, Guiot, Luke, Appleyard, Thomas, Robinson, Karen, Fong, Angus, Watts, Anna, Stedman, Tobias, Walton, Victoria, Inman, Dominic, Liaw, Frank, Hadfield, James, McGovern, Julia, Baldock, Thomas, White, Jonathan, Seah, Matthew, Jacob, Neville, Ali, Zaid Haj, Goff, Thomas, Sanalla, Ahmed, Gomati, Ayoub, Nordin, Louise, Hassan, Eslam, Ramadan, Omar, Teoh, Kar Hao, Baskaran, Dinnish, Ngwayi, James, Abbakr, Lina, Blackmore, Noah, Mansukhani, Sameer, Guryel, Enis, Harper, Adam, Cashman, Emily, Brooker, Joanne, Pack, Louise, Regan, Nora, Wagner, Wilhelm, Selim, Amr, Archer, Debbie, McConaghie, Gregory, Patel, Ravi, Gibson, William, Pasapula, Chandra S, Youssef, Hesham, Aziz, Md Abdul, Subhash, Sadhin, Banaszkiewicz, Paul, Elzawahry, Ahmed, Neo, Chryssa, Wei, Nicholas, Bhaskaran, Arun, Sharma, Abhishek, Factor, Danielle, Shahin, Fatma, Shields, David, Ferreira, Catarina Dores Fernandes, Jeyakumar, Gowsikan, Liao, Quintin, Sinnerton, Robert, Ashwood, Neil, Sarhan, Islam, Ker, Andrew, Phelan, Sean, Paxton, James, McAuley, Joseph, Moulton, Lawrence, Mohamed, Ahmed, Dias, Ana, Ho, Beatrice, Francis, Daniel, Miller, Sarah, Phillips, Jon, Jones, Robin, Arthur, Calum, Oag, Erlend, Thutoetsile, Kamogelo, Bell, Katrina, Milne, Kirsty, Whitefield, Reiss, Patel, Kuntal, Singh, Abhimanyu, Morris, Geraint, Parkinson, Dawn, Patil, Amogh, Hamid, Hassan, Syam, Kevin, Singh, Rohit, Menon, Deepak, Crooks, Sophie, Borland, Steven, Rohman, Adam, Nicholson, Alys, Smith, Ben, Hafiz, Nauman, Kolhe, Shivam, Waites, Matthew, Piper, Dani, Westacott, David, Grimshaw, Jessica, Bott, Alasdair, Berry, Alexander, Battle, Joseph, Flannery, Oliver, Iyengar, Karthikeyan P, Thakur, Abdul Wadood, Yousef, Mina, Bansod, Vaibhav, El-nahas, Walaa, Dawe, Edward, Oladeji, Emmanuel, Federer, Simon, Trompeter, Alex, Pritchard, Anna, Shurovi, Badrun, Jordan, Chris, Little, Max, Sivaloganathan, Sivanshankar, Shaunak, Shalin, Watters, Hazel, Luck, Joshua, Zbaeda, Mohamed, Frasquet-Garcia, Antonio, Warner, Christian, Telford, Jeremy, Rooney, Joanna, Attwood, Joseph, Wilson, Faye, Panagiotopoulos, Andreas, Keane, Conal, Scott, Helen, Mazel, Rebecca, Maggs, Joanna, Skinner, Edward, McMunn, Finlay, Lau, Joshua, Ravikumar, Kasetti, Thakker, Dev, Gill, Moneet, McCarthy, Phillip, Fossey, Gavin, Shah, Sohaib, McAlinden, Gavan, McGoldrick, Peter, O'Brien, Scarlett, Patil, Sunit, Millington, Antonia, Umar, Hamza, Sehdev, Simran, Dyer-Hill, Thomas, Yu Kwan, Tsun, Tanagho, Andy, Hagnasir, Ahmed, White, Thomas, Bano, Christopher, Kissin, Eleanor, Ghani, Rafia, Thomas, Philip S W, McMullan, Mark, Walmsley, Matthew, Elgendy, Mohamed, Winstanley, Robert, Round, Joanne, Baxter, Mark, Thompson, Emett, Hogan, Kathryn, Youssef, Khaled, Fetouh, Sherif, Hopper, Graeme P, Simpson, Cameron, Warren, Craig, Waugh, Dominic, Nair, Gopikrishnan, Ballantyne, Andy, Blacklock, Calum, O'Connell, Ciara, Toland, Gemma, McIntyre, Joshua, Ross, Lauren, Badge, Ravindra, Loganathan, Deeraj, Turner, Ian, Ball, Matthew, Maqsood, Saad, Deierl, Krisztian, Beer, Alexander, Tan, Arthur Chen Wun, Mackinnon, Thomas, Gade, Venkat, Gill, James, Yu San, Kay, Archunan, Maheswaran Warren, Shaikh, Mariyam, Ugbah, Onyinye, Uwaoma, Sade, Pillai, Anand, Nath, Upamanyu, Rohan, Farhan-Alanie, M. M., Dixon, J., Irvine, S., Walker, R., and Eardley, W. G. P.

Published
2024
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18. The impact of anticoagulant medications on fragility femur fracture care: The hip and femoral fracture anticoagulation surgical timing evaluation (HASTE) study

Author

Smith, Matthew, Yoong, Andrel, Lim, Jun Wei, Yousef, Omar, McDonald, Stephen, Chileshe, Chinga, Ramus, Camilla, Clements, Christopher, Barrett, Liam, Rockall, Oliver, Geetala, Rahul, Islam, Saif Ul, Nasar, Ahmad, Almond, Kieran, Hassan, Ladan Fatima Yusuf, Shah, Sohan, Brand, Robert Bruce, Yawar, Bakhat, Gilmore, Catherine, McAuley, Daryl, Khan, Waleed, Subramanian, Padmanabhan, Ahluwalia, Aashish, Ozbek, Leyla, Awasthi, Prashant, Sheikh, Hassaan, Barkley, Sarah, Ardolino, Toni, Denning, Alexander, Thiruchandran, Gaj, Fraig, Hossam, Salim, Omar, Iqbal, Rabia, Guy, Stephen, Hogg, Jack, Bagshaw, Oliver, Asmar, Samir, Mitchell, Stephen, Quek, Fang, Fletcher, James, French, Jonathan, Graham, Selina, Sloper, Philip, Sadique, Hammad, Matera, Valentina, Sohail, Zain, Leong, Justin Wei, Issa, Fares, Greasley, Lauren, Marsden, Samuel, Parry, Lucy, Mannan, Syed, Zaheen, Humayoon, Moriarty, Peter, Manning, William, Morris, Timothy, Brockbanks, Carole, Ward, Peter, Pearce, Kim, McMenemy, Louise, Mahmoud, Mohamed, Kieffer, Will, Lal, Aayush, Collis, Justin, Chandrasekaran, Karthik, Foxall-Smith, Michael, Raad, Marjan, Kempshall, Peter, Cheuk, Jocelyn, Leckey, Sam, Gupta, Rishav, Engelke, Daniel, Kemp, Mark, Venkatesan, Aakaash, Hussain, Adnan, Simons, Michiel, Raghavendra, Ram Mohan, Rohra, Satish, Deo, Sunny, Vasarhelyi, Ferenc, Thelwall, Claire, Cullen, Krista, Al-Obaidi, Bilal, Fell, Adam, Thaumeen, Ahmad, Dadabhoy, Maria, Ali, Mira, Ijaz, Sameer, Lin, David, Khan, Basharat, Alsonbaty, Mohamed, Lebe, Moritz, Millan, Ravi Kant, Imam, Sam, Theobald, Emma, Cormack, Jonathan, Sharoff, Lokesh, Eаrdley, Will, Jeyapalan, Rathan, Alcock, Liam, Clayton, Julia, Bates, Natalie, Mahmoud, Yousif, Osborne, Alex, Ralhan, Shvaita, Carpenter, Catriona, Ahmad, Mahmood, Ravi, Sanjeev Musuvathy, Konbaz, Tarek, Lloyd, Thomas, Sheikh, Nomaan, Swealem, Ahmed, Soroya, Emma, Rayan, Faizal, Ward, Thomas, Vasireddy, Aswinkumar, Clarke, Ellisiv, Sikdar, Oishi, Smart, Yat Wing, Windley, Joseph, Ilagan, Belen, Brophy, Edel, Joseph, Sarah, Lowery, Kathryn, Jamjoom, Ammer, Ismayl, Ghiath, Aujla, Randeep, Sambhwani, Sharan, Ramasamy, Arul, Khalaf, Ahmed, Ponugoti, Nikhil, Teng, Wai Huang, Masud, Saqib, Otoibhili, Eghe, Clarkson, Martin, Nafea, Mohamed, Sarhan, Mohamed, Hanna, Shady, Kelly, Andrew, Curtis, Alex, Gourbault, Lysander, Tarhini, Mariam, Platt, Nicholas, Fleming, Thomas, Pemmaraju, Gopalakrishna, Choudri, Mohammed Junaid, Burahee, Abdus, Hassan, Labiba, Hamid, Laveeza, Loveday, David, Edres, Kareem, Schankat, Kerstin, Granger, Luke, Goodbun, Matthew, Parikh, Sunny, Johnson-Lynn, Sarah, Griffiths, Alexandra, Rai, Avinash, Chandler, Henry, Guiot, Luke, Appleyard, Thomas, Robinson, Karen, Fong, Angus, Watts, Anna, Stedman, Tobias, Walton, Victoria, Inman, Dominic, Liaw, Frank, Hadfield, James, McGovern, Julia, Baldock, Thomas, White, Jonathan, Seah, Matthew, Jacob, Neville, Ali, Zaid Haj, Goff, Thomas, Sanalla, Ahmed, Gomati, Ayoub, Nordin, Louise, Hassan, Eslam, Ramadan, Omar, Teoh, Kar Hao, Baskaran, Dinnish, Ngwayi, James, Abbakr, Lina, Blackmore, Noah, Mansukhani, Sameer, Guryel, Enis, Harper, Adam, Cashman, Emily, Brooker, Joanne, Pack, Louise, Regan, Nora, Wagner, Wilhelm, Selim, Amr, Archer, Debbie, McConaghie, Gregory, Patel, Ravi, Gibson, William, Pasapula, Chandra S, Youssef, Hesham, Aziz, Md Abdul, Subhash, Sadhin, Banaszkiewicz, Paul, Elzawahry, Ahmed, Neo, Chryssa, Wei, Nicholas, Bhaskaran, Arun, Sharma, Abhishek, Factor, Danielle, Shahin, Fatma, Shields, David, Ferreira, Catarina Dores Fernandes, Jeyakumar, Gowsikan, Liao, Quintin, Sinnerton, Robert, Ashwood, Neil, Sarhan, Islam, Ker, Andrew, Phelan, Sean, Paxton, James, McAuley, Joseph, Moulton, Lawrence, Mohamed, Ahmed, Dias, Ana, Ho, Beatrice, Francis, Daniel, Miller, Sarah, Phillips, Jon, Jones, Robin, Arthur, Calum, Oag, Erlend, Thutoetsile, Kamogelo, Bell, Katrina, Milne, Kirsty, Whitefield, Reiss, Patel, Kuntal, Singh, Abhimanyu, Morris, Geraint, Parkinson, Dawn, Patil, Amogh, Hamid, Hassan, Syam, Kevin, Singh, Rohit, Menon, Deepak, Crooks, Sophie, Borland, Steven, Rohman, Adam, Nicholson, Alys, Smith, Ben, Hafiz, Nauman, Kolhe, Shivam, Waites, Matthew, Piper, Dani, Westacott, David, Grimshaw, Jessica, Bott, Alasdair, Berry, Alexander, Battle, Joseph, Flannery, Oliver, Iyengar, Karthikeyan P, Thakur, Abdul Wadood, Yousef, Mina, Bansod, Vaibhav, El-nahas, Walaa, Dawe, Edward, Oladeji, Emmanuel, Federer, Simon, Trompeter, Alex, Pritchard, Anna, Shurovi, Badrun, Jordan, Chris, Little, Max, Sivaloganathan, Sivanshankar, Shaunak, Shalin, Watters, Hazel, Luck, Joshua, Zbaeda, Mohamed, Frasquet-Garcia, Antonio, Warner, Christian, Telford, Jeremy, Rooney, Joanna, Attwood, Joseph, Wilson, Faye, Panagiotopoulos, Andreas, Keane, Conal, Scott, Helen, Mazel, Rebecca, Maggs, Joanna, Skinner, Edward, McMunn, Finlay, Lau, Joshua, Ravikumar, Kasetti, Thakker, Dev, Gill, Moneet, McCarthy, Phillip, Fossey, Gavin, Shah, Sohaib, McAlinden, Gavan, McGoldrick, Peter, O'Brien, Scarlett, Patil, Sunit, Millington, Antonia, Umar, Hamza, Sehdev, Simran, Dyer-Hill, Thomas, Yu Kwan, Tsun, Tanagho, Andy, Hagnasir, Ahmed, White, Thomas, Bano, Christopher, Kissin, Eleanor, Ghani, Rafia, Thomas, Philip S W, McMullan, Mark, Walmsley, Matthew, Elgendy, Mohamed, Winstanley, Robert, Round, Joanne, Baxter, Mark, Thompson, Emett, Hogan, Kathryn, Youssef, Khaled, Fetouh, Sherif, Hopper, Graeme P, Simpson, Cameron, Warren, Craig, Waugh, Dominic, Nair, Gopikrishnan, Ballantyne, Andy, Blacklock, Calum, O'Connell, Ciara, Toland, Gemma, McIntyre, Joshua, Ross, Lauren, Badge, Ravindra, Loganathan, Deeraj, Turner, Ian, Ball, Matthew, Maqsood, Saad, Deierl, Krisztian, Beer, Alexander, Tan, Arthur Chen Wun, Mackinnon, Thomas, Gade, Venkat, Gill, James, Yu San, Kay, Archunan, Maheswaran Warren, Shaikh, Mariyam, Ugbah, Onyinye, Uwaoma, Sade, Pillai, Anand, Nath, Upamanyu, Rohan, Farhan-Alanie, M.M., Chinweze, R., Walker, R., and Eardley, W.G.P.

Published
2024
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22. Day of the storm trooper

Author

Fleming, Thomas

Subjects
WORLD WAR I - Campaigns and Battles, ATTACK AND DEFENSE (MILITARY SCIENCE) - History, TACTICS - History, MILITARY ART AND SCIENCE - History, WORLD WAR I - Lessons Learned
Abstract

illus por map bibliog

Published
1992

23. From the Battle of Carillon

Author

Fleming, Thomas

Subjects
FRENCH AND INDIAN WAR, 1755-1763 - Campaigns and Battles, BATTLES - Lessons Learned
Abstract

illus

Published
2008

24. Maximal knotless graphs

Author

Eakins, Lindsay, Fleming, Thomas, and Mattman, Thomas W.

Subjects
Mathematics - Geometric Topology, Mathematics - Combinatorics, 05C10 (Primary) 57M15, 57K10 (Secondary)
Abstract

A graph is maximal knotless if it is edge maximal for the property of knotless embedding in $R^3$. We show that such a graph has at least $\frac74 |V|$ edges, and construct an infinite family of maximal knotless graphs with $|E| < \frac52|V|$. With the exception of $|E| = 22$, we show that for any $|E| \geq 20$ there exists a maximal knotless graph of size $|E|$. We classify the maximal knotless graphs through nine vertices and 20 edges. We determine which of these maxnik graphs are the clique sum of smaller graphs and construct an infinite family of maxnik graphs that are not clique sums., Comment: 14 pages, 3 figures v2: substantial revisions. Improved Theorem 4.5. Added Section 5

Published
2021
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25. When to update COVID-19 vaccine composition

Author

Grant, Rebecca, Sacks, Jilian A., Abraham, Priya, Chunsuttiwat, Supamit, Cohen, Cheryl, Figueroa, J. Peter, Fleming, Thomas, Fine, Paul, Goldblatt, David, Hasegawa, Hideki, MacIntrye, C. Raina, Memish, Ziad A., Miller, Elizabeth, Nishioka, Sergio, Sall, Amadou A., Sow, Samba, Tomori, Oyewale, Wang, Youchun, Van Kerkhove, Maria D., Wambo, Marie-Ange, Cohen, Homa Attar, Mesfin, Samuel, Otieno, James R., Subissi, Lorenzo, Briand, Sylvie, Wentworth, David E., and Subbarao, Kanta

Published
2023
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27. Classifying Intrinsically Linked Tournaments by Score Sequence

Author

Fleming, Thomas and Foisy, Joel

Subjects
Mathematics - Geometric Topology, Mathematics - Combinatorics, 57M15, 57M25, 05C10, 05C20
Abstract

A tournament on 8 or more vertices may be intrinsically linked as a directed graph. We begin the classification of intrinsically linked tournaments by examining their score sequences. While many distinct tournaments may have the same score sequence, there exist score sequences $S$ such that any tournament with score sequence $S$ has an embedding with no nonsplit consistently oriented link. We call such score sequences $\textit{linkless}$, and we show that the vast majority of score sequences for 8 vertex tournaments are linkless. We also extend these results to $n$ vertex tournaments and are able to classify many longer score sequences as well. We show that for any $n$, there exist at least $O(n)$ linkless score sequences, but we conjecture that the fraction of score sequences of length $n$ that are linkless goes to 0 as $n$ becomes large., Comment: 19 pages, 5 figures. The paper has been reorganized and condensed. Interested readers can find detailed proofs of all of the results in version 1

Published
2020

31. Partisanship and personal vote-seeking in parliamentary behaviour

Author

Fleming, Thomas G. and Zubek, Radoslaw

Subjects
324
Abstract

Incumbent politicians can use parliamentary behaviour to generate a 'personal vote': electoral support attracted to an individual candidate rather than their party label. This personal vote-seeking has consequences for accountability, representation, and policymaking, yet its prevalence varies extensively. Existing explanations of this variation focus on the consequences of electoral institutions and the characteristics of individual members of parliament (MPs). This thesis adds to a much smaller literature linking MPs' personal vote-seeking to characteristics of its intended audience: voters. Specifically, I argue that partisanship among voters reduces MPs' incentives for engaging in personal vote-seeking, by limiting its effectiveness. When voters have stronger ties to political parties, they are less likely to reward or punish MPs for their individual qualities and performance. As a consequence, lower partisanship among citizens should lead to more extensive personal vote-seeking by MPs. I test this argument in two stages. First, I test its voter-level implications. Using a quasi-experiment in New Zealand and a survey experiment in the United Kingdom (UK), I find evidence that partisanship does make voters less likely to reward MPs for their individual behaviour in parliament. Second, I test its MP-level implications. Analysing legislative behaviour in the UK House of Commons, I find evidence that MPs' personal vote-seeking efforts can be linked to variation in voters' partisanship over time, and (less consistently) between constituencies. Taken together, these findings offer new evidence that voters' relationships with political parties shape MPs' electoral strategies and parliamentary behaviour. This suggests an important link between how voters think about politics, and how their representatives conduct it.

Published
2020

36. Intrinsic linking and knotting in tournaments

Author

Fleming, Thomas and Foisy, Joel

Subjects
Mathematics - Geometric Topology, Mathematics - Combinatorics, 57M15, 57M25, 05C10, 05C20
Abstract

A directed graph $G$ is $\textit{intrinsically linked}$ if every embedding of that graph contains a non-split link $L$, where each component of $L$ is a consistently oriented cycle in $G$. A $\textit{tournament}$ is a directed graph where each pair of vertices is connected by exactly one directed edge. We consider intrinsic linking and knotting in tournaments, and study the minimum number of vertices required for a tournament to have various intrinsic linking or knotting properties. We produce the following bounds: intrinsically linked ($n=8$), intrinsically knotted ($9 \leq n \leq 12$), intrinsically 3-linked ($10 \leq n \leq 23$), intrinsically 4-linked ($12 \leq n \leq 66$), intrinsically 5-linked ($15 \leq n \leq 154$), intrinsically $m$-linked ($3m \leq n \leq 8(2m-3)^2$), intrinsically linked with knotted components ($9 \leq n \leq 107$), and the disjoint linking property ($12 \leq n \leq 14$). We also introduce the $\textit{consistency gap}$, which measures the difference in the order of a graph required for intrinsic $n$-linking in tournaments versus undirected graphs. We conjecture the consistency gap to be non-decreasing in $n$, and provide an upper bound at each $n$., Comment: 16 pages, 4 figures

Published
2019

39. Monitoring overall survival in pivotal trials in indolent cancers

Author

Fleming, Thomas R, primary, Hampson, Lisa V, additional, Bharani, Bharani-Dharan, additional, Bretz, Frank, additional, Chakravartty, Arunava, additional, Coroller, Thibaud, additional, Koukouli, Evanthia, additional, Wittes, Janet, additional, Yateman, Nigel, additional, and Zuber, Emmanuel, additional

Published
2024
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40. #2909 Molecular mechanisms of early vascular damage in children with chronic renal failure

Author

Bartosova, Maria, primary, Messerschmidt, Gesine, additional, Saleem, Arslan, additional, Bauer, Sarah, additional, Bernardor, Julie, additional, Fleming, Thomas, additional, Helm, Dominic, additional, Holle, Johannes Benjamin, additional, Kratochwill, Klaus, additional, Peters, Verena, additional, Hausmann, Michael, additional, and Schmitt, Claus Peter, additional

Published
2024
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42. FDA/Arthritis Foundation osteoarthritis drug development workshop recap: Assessment of long-term benefit

Author

Kim, Jason S., Borges, Silvana, Clauw, Daniel J., Conaghan, Philip G., Felson, David T., Fleming, Thomas R., Glaser, Rachel, Hart, Elizabeth, Hochberg, Marc, Kim, Yura, Kraus, Virginia B., Lapteva, Larissa, Li, Xiaojuan, Majumdar, Sharmila, McAlindon, Timothy E., Mobasheri, Ali, Neogi, Tuhina, Roemer, Frank W., Rothwell, Rebecca, Shibuya, Robert, Siegel, Jeffrey, Simon, Lee S., Spindler, Kurt P., and Nikolov, Nikolay P.

Published
2022
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43. Elevated markers of DNA damage and senescence are associated with the progression of albuminuria and restrictive lung disease in patients with type 2 diabetesResearch in context

Author

Kumar Varun, Kender Zoltan, Sulaj Alba, Blume Manuel, Kliemank Elisabeth, Tsilingiris Dimitrios, Groener Jan B, Brune Maik, Shahzad Khurrum, Isermann Berend, Herzig Stephen, Fleming Thomas, Szendroedi Julia, Nawroth Peter, and Kopf Stefan

Subjects
Type 2 diabetes mellitus, Diabetic complications, DNA-damage, Senescence, Senescence-associated secretory phenotype, Diabetic kidney disease, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: This study was conducted to investigate the cascade involving DNA damage, senescence, and senescence-associated secretory phenotype (SASP) in experimental diabetes and in a four-year follow-up study in patients with pre-diabetes and type 2 diabetes. Methods: Kidney, lung, and liver were studied in 4 months diabetic db/db mice and age-matched controls for the presence of DNA damage and fibrosis. DNA damage (comet-tail-length and ɤH2Ax-positivity in white blood cells), urinary p21-excretion, and plasma IL-6 and TGF-β1 were determined from 115 healthy participants, 34 patients with pre-diabetes and 221 with type 2 diabetes. Urinary albumin-creatinine-ratio, lung function, and transient elastography of the liver were performed in a prospective follow-up study over 4 years. Findings: db/db mice showed an increased nuclear ɤH2AX signal in all tissues as compared to the background control. Markers for DNA damage, senescence, and SASP were increased in patients with diabetes. The presence of nephropathy, restrictive lung disease (RLD), and increased liver stiffness was in a cross-sectional design associated with increased markers for DNA damage, senescence, and SASP. The progression of nephropathy over 4 years was predicted by increased DNA damage, senescence, and SASP, while the progression of RLD was associated with increased DNA damage and IL-6 only. The progression of liver stiffness was not associated with any of these parameters. HbA1c was not predictive for progression. Interpretation: In db/db mice, the cascade of DNA damage is associated with diabetes-related complications. In patients with diabetes, the progression of complications in the kidney and lung is predicted by markers reflecting DNA damage, and senescence-triggered organ fibrosis. Funding: This work was supported by the German Research Foundation (DFG) in the CRC 1118 and CRC 1158, by the GRK DIAMICOM, by the German Center for Diabetes Research (DZD e.V.), and by the Ministry of Science, Research and the Arts, Baden-Württemberg (Kompetenznetzwerk Präventivmedizin).

Published
2023
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44. Safety and efficacy of ganaxolone in patients with CDKL5 deficiency disorder: results from the double-blind phase of a randomised, placebo-controlled, phase 3 trial

Author

Belousova, Elena, Belyaev, Oleg, Ben-Zeev, Bruria, Brunklaus, Andreas, Ciliberto, Michael A., Darra, Francesca, Davis, Ronald, De Giorgis, Valentina, Doronina, Olga, Fahey, Michael, Guerrini, Renzo, Heydemann, Peter, Khaletskaya, Olga, Lisewski, Pawel, Marsh, Eric D., Moosa, Ahsan N., Perry, Scott, Philip, Sunny, Rajaraman, Rajsekar R., Renfroe, Ben, Saneto, Russell P., Scheffer, Ingrid E., Sogawa, Yoshimi, Suter, Bernhardt, Sweney, Matthew T., Tarquinio, Daniel, Veggiotti, Pierangelo, Wallace, Geoff, Weisenberg, Judy, Wilfong, Angus, Wirrell, Elaine C., Zafar, Muhammad, Zolnowska, Marta, Knight, Elia M Pestana, Amin, Sam, Bahi-Buisson, Nadia, Benke, Tim A, Cross, J Helen, Demarest, Scott T, Olson, Heather E, Specchio, Nicola, Fleming, Thomas R, Aimetti, Alex A, Gasior, Maciej, and Devinsky, Orrin

Published
2022
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46. Intrinsically Knotted and 4-Linked Directed Graphs

Author

Fleming, Thomas and Foisy, Joel

Subjects
Mathematics - Geometric Topology, Mathematics - Combinatorics
Abstract

We consider intrinsic linking and knotting in the context of directed graphs. We construct an example of a directed graph that contains a consistently oriented knotted cycle in every embedding. We also construct examples of intrinsically 3-linked and 4-linked directed graphs. We introduce two operations, consistent edge contraction and H-cyclic subcontraction, as special cases of minors for digraphs, and show that the property of having a linkless embedding is closed under these operations. We analyze the relationship between the number of distinct knots and links in an undirected graph $G$ and its corresponding symmetric digraph $\overline{DG}$. Finally, we note that the maximum number of edges for a graph that is not intrinsically linked is $O(n)$ in the undirected case, but $O(n^2)$ for directed graphs., Comment: 15 pages, 7 figures Correction to Lemma 4.1

Published
2017

47. The origins of centralized agenda control at Westminster: Consensus or controversy?

Author

Fleming, Thomas G., Hix, Simon, and Zubek, Radoslaw

Subjects
*POLITICAL parties, *LEGAL evidence, *TWENTIETH century, *LEGISLATIVE bodies, *REFORMS
Abstract

Centralized agenda control is a feature of many parliaments, with important consequences for the conduct and outcomes of legislative politics. Much previous work has thus sought to understand the emergence of centralized agenda‐setting rules. We extend this literature by studying the “Balfour reforms”, which centralized agenda control in the early twentieth century UK House of Commons. Our aim is to probe a conventional claim in the existing literature: that the opposition supported these reforms. This is a counter‐intuitive claim, which rests on relatively little direct evidence. We analyze historical roll‐call data from 1902 to assess how far the opposition supported agenda centralization. We complement this analysis by examining attempted amendments and speech contributions to parliamentary debates. Contrary to the standard view, we find that the primary opposition party consistently resisted these reforms. This evidence of controversy rather than consensus revises our understanding of a key milestone in the development of the Westminster parliament, and contributes to the wider literature on the choice of agenda‐setting procedures. [ABSTRACT FROM AUTHOR]

Published
2024
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48. The Case for Access to Data Monitoring Committee Charters.

Author

Zarin, Deborah, Wittes, Janet T., Fleming, Thomas R., Rockhold, Frank, Ellenberg, Susan, and DeMets, David L.

Subjects
MEDICAL protocols, CLINICAL trials, MEMBERSHIP, ORGANIZATIONAL structure, ACCESS to information
Abstract

Clinical trials investigating novel or high-risk interventions often use data monitoring committees (DMCs) to ensure that the participants' best interests are safeguarded. The typical DMC charter describes procedures by which the DMC operates, including important details concerning organizational structure, membership, meeting frequency, statistical monitoring guidelines, and contents of DMC reports for interim review. These charters, however, are not routinely publicly available; in some cases, their access could be important to the interpretation of trial results. We recommend including DMC charters for such trials in ClinicalTrials.gov at the time of trial completion; trial protocols, informed consent documents, and statistical analysis plans are already available in this repository. [ABSTRACT FROM AUTHOR]

Published
2024
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49. Glucose Load Following Prolonged Fasting Increases Oxidative Stress– Linked Response in Individuals With Diabetic Complications.

Author

von Rauchhaupt, Ekaterina, Rodemer, Claus, Kliemank, Elisabeth, Bulkescher, Ruben, Campos, Marta, Kopf, Stefan, Fleming, Thomas, Herzig, Stephan, Nawroth, Peter P., Szendroedi, Julia, Zemva, Johanna, and Sulaj, Alba

Subjects
MONONUCLEAR leukocytes, TYPE 2 diabetes, CITRATE synthase, DIABETES complications, GENE expression, GLUCOSE tolerance tests
Abstract

OBJECTIVE: Prolonged catabolic states in type 2 diabetes (T2D), exacerbated by excess substrate flux and hyperglycemia, can challenge metabolic flexibility and antioxidative capacity. We investigated cellular responses to glucose load after prolonged fasting in T2D. RESEARCH DESIGN AND METHODS: Glucose-tolerant individuals (CON, n = 10) and individuals with T2D with (T2D+, n = 10) and without (T2D−, n = 10) diabetes complications underwent oral glucose tolerance test before and after a 5-day fasting-mimicking diet. Peripheral blood mononuclear cell (PBMC) resistance to ex vivo dicarbonyl methylglyoxal (MG) exposure after glucose load was assessed. Markers of dicarbonyl detoxification, oxidative stress, and mitochondrial biogenesis were analyzed by quantitative PCR, with mitochondrial complex protein expression assessed by Western blotting. RESULTS: T2D+ exhibited decreased PBMC resistance against MG, while T2D− resistance remained unchanged, and CON improved postglucose load and fasting (−19.0% vs. −1.7% vs. 12.6%; all P = 0.017). T2D+ showed increased expression in dicarbonyl detoxification (mRNA glyoxalase-1, all P = 0.039), oxidative stress (mRNA glutathione-disulfide-reductase, all P = 0.006), and mitochondrial complex V protein (all P = 0.004) compared with T2D− and CON postglucose load and fasting. Citrate synthase activity remained unchanged, indicating no change in mitochondrial number. Mitochondrial biogenesis increased in T2D− compared with CON postglucose load and fasting (mRNA HspA9, P = 0.032). T2D−, compared with CON, exhibited increased oxidative stress postfasting, but not postglucose load, with increased mRNA expression in antioxidant defenses (mRNA forkhead box O4, P = 0.036, and glutathione-peroxidase-2, P = 0.034), and compared with T2D+ (glutathione-peroxidase-2, P = 0.04). CONCLUSIONS: These findings suggest increased susceptibility to glucose-induced oxidative stress in individuals with diabetes complications after prolonged fasting and might help in diet interventions for diabetes management. [ABSTRACT FROM AUTHOR]

Published
2024
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50. Diseases Caused by Pectobacterium and Dickeya Species Around the World

Author

van der Wolf, Jan M., Acuña, Ivette, De Boer, Solke H., Brurberg, May B., Cahill, Greig, Charkowski, Amy O., Coutinho, Teresa, Davey, Triona, Dees, Merete W., Degefu, Yeshitila, Dupuis, Brice, Elphinstone, John G., Fan, Jiaqin, Fazelisanagri, Esmaeil, Fleming, Thomas, Gerayeli, Nahid, Gorshkov, Vladimir, Helias, Valérie, le Hingrat, Yves, Johnson, Steven B., Keiser, Andreas, Kellenberger, Isabelle, Li, Xiang (Sean), Lojkowska, Ewa, Martin, Rodney, Perminow, Juliana Irina, Petrova, Olga, Motyka-Pomagruk, Agata, Rossmann, Simeon, Schaerer, Santiago, Sledz, Wojciech, Toth, Ian K., Tsror, Leah, van der Waals, Jacquie E., de Werra, Patrice, Yedidia, Iris, Van Gijsegem, Frédérique, editor, van der Wolf, Jan M., editor, and Toth, Ian K., editor

Published
2021
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