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2,631 results on '"Barrett C"'

1. Exploration-based learning of a stabilizing controller predicts locomotor adaptation

Author

Nidhi Seethapathi, Barrett C. Clark, and Manoj Srinivasan

Subjects
Science
Abstract

Abstract Humans adapt their locomotion seamlessly in response to changes in the body or the environment. It is unclear how such adaptation improves performance measures like energy consumption or symmetry while avoiding falling. Here, we model locomotor adaptation as interactions between a stabilizing controller that reacts quickly to perturbations and a reinforcement learner that gradually improves the controller’s performance through local exploration and memory. This model predicts time-varying adaptation in many settings: walking on a split-belt treadmill (i.e. with both feet at different speeds), with asymmetric leg weights, or using exoskeletons — capturing learning and generalization phenomena in ten prior experiments and two model-guided experiments conducted here. The performance measure of energy minimization with a minor cost for asymmetry captures a broad range of phenomena and can act alongside other mechanisms such as reducing sensory prediction error. Such a model-based understanding of adaptation can guide rehabilitation and wearable robot control.

Published
2024
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2. Ryanodine receptor 1-mediated Ca2+ signaling and mitochondrial reprogramming modulate uterine serous cancer malignant phenotypes

Author

Li Zhang, Chi-Lam Au-Yeung, Chunxian Huang, Tsz-Lun Yeung, Sammy Ferri-Borgogno, Barrett C. Lawson, Suet-Ying Kwan, Zheng Yin, Stephen T. Wong, Vienna Thomas, Karen H. Lu, Kay-Pong Yip, James S. K. Sham, and Samuel C. Mok

Subjects
RYR1, USC, AKT/CREB/PGC-1α signaling pathway and AKT/HK1/2 signaling pathway, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Uterine serous cancer (USC) is the most common non-endometrioid subtype of uterine cancer, and is also the most aggressive. Most patients will die of progressively chemotherapy-resistant disease, and the development of new therapies that can target USC remains a major unmet clinical need. This study sought to determine the molecular mechanism by which a novel unfavorable prognostic biomarker ryanodine receptor 1 (RYR1) identified in advanced USC confers their malignant phenotypes, and demonstrated the efficacy of targeting RYR1 by repositioned FDA-approved compounds in USC treatment. Methods TCGA USC dataset was analyzed to identify top genes that are associated with patient survival or disease stage, and can be targeted by FDA-approved compounds. The top gene RYR1 was selected and the functional role of RYR1 in USC progression was determined by silencing and over-expressing RYR1 in USC cells in vitro and in vivo. The molecular mechanism and signaling networks associated with the functional role of RYR1 in USC progression were determined by reverse phase protein arrays (RPPA), Western blot, and transcriptomic profiling analyses. The efficacy of the repositioned compound dantrolene on USC progression was determined using both in vitro and in vivo models. Results High expression level of RYR1 in the tumors is associated with advanced stage of the disease. Inhibition of RYR1 suppressed proliferation, migration and enhanced apoptosis through Ca2+-dependent activation of AKT/CREB/PGC-1α and AKT/HK1/2 signaling pathways, which modulate mitochondrial bioenergetics properties, including oxidative phosphorylation, ATP production, mitochondrial membrane potential, ROS production and TCA metabolites, and glycolytic activities in USC cells. Repositioned compound dantrolene suppressed USC progression and survival in mouse models. Conclusions These findings provided insight into the mechanism by which RYR1 modulates the malignant phenotypes of USC and could aid in the development of dantrolene as a repurposed therapeutic agent for the treatment of USC to improve patient survival.

Published
2022
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6. Discovering structural cis‐regulatory elements by modeling the behaviors of mRNAs

Author

Barrett C Foat and Gary D Stormo

Subjects
modeling, mRNA stability, polysome association, post‐transcriptional regulation, secondary structure, Biology (General), QH301-705.5, Medicine (General), R5-920
Abstract

Abstract Gene expression is regulated at each step from chromatin remodeling through translation and degradation. Several known RNA‐binding regulatory proteins interact with specific RNA secondary structures in addition to specific nucleotides. To provide a more comprehensive understanding of the regulation of gene expression, we developed an integrative computational approach that leverages functional genomics data and nucleotide sequences to discover RNA secondary structure‐defined cis‐regulatory elements (SCREs). We applied our structural cis‐regulatory element detector (StructRED) to microarray and mRNA sequence data from Saccharomyces cerevisiae, Drosophila melanogaster, and Homo sapiens. We recovered the known specificities of Vts1p in yeast and Smaug in flies. In addition, we discovered six putative SCREs in flies and three in humans. We characterized the SCREs based on their condition‐specific regulatory influences, the annotation of the transcripts that contain them, and their locations within transcripts. Overall, we show that modeling functional genomics data in terms of combined RNA structure and sequence motifs is an effective method for discovering the specificities and regulatory roles of RNA‐binding proteins.

Published
2009
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9. How a Losing Team like the Canadiens can Steal a Stanley Cup: A Quantitative Intransitive Hockey Analysis

Author

Barrett, C. J., Koumarianos, S., and Mermut, O.

Subjects
Mathematics - History and Overview
Abstract

We present here a simple mathematical model that provides a successful strategy, quantitatively, to ending the continued championship futility experienced by Canadian Hockey Teams. Competitive Intransitivity is used here as a simple predictive framework to capture how investing strategically, under a uniform salary cap, in just 3 independently variable aspects of the sport (such as Offence, Defence, and a Goaltender), by just 3 Hockey Teams applying differing salary priorities (such as Montreal, Boston, and New York), can lead to rich and perhaps surprisingly unexpected outcomes in play, similar to rolling intransitive dice together in a series of head-to-head games. A possibly fortunate conclusion of this analysis is the prediction that for any Team's chosen strategy (such as New York's), a counter strategy within the same salary cap can be adopted by a playoff opponent (such as Montreal) which will prove victorious over a long playoff series, enabling a pathway to end prolonged championship futility., Comment: Minor typographical errors corrected, no changes to mathematics. Minor wording improvements offered to update example teams for more current relevance, including title

Published
2021

10. Atomistic simulations of the interaction of basal dislocations with MgZn$_2$ precipitates in Mg alloys

Author

Esteban-Manzanares, G., Alizadeh, R., Papadimitriou, I., Dickel, D., Barrett, C. D., and LLorca, J.

Subjects
Condensed Matter - Materials Science
Abstract

The interaction between Mg edge basal dislocations and rod-shaped $\beta_1'$-MgZn$_2$ precipitates was studied by atomistic simulations using a new interatomic potential. The atomistic model was carefully built taking into account the experimental information about the orientation relationship between the matrix and the precipitate to ensure minimum energy interfaces. It was found that the dislocations initially overcame the precipitate by the formation of an Orowan loop that penetrated in the precipitate. The precipitate was finally sheared after several Orowan loops were piled-up. The number of loops necessary to shear the precipitate decreased as precipitate cross-section decreased and the temperature increased but was independent of the precipitate spacing. Precipitate shearing did not take place along well-defined crystallographic planes but it was triggered by the accumulation of the elastic energy in the precipitate which finally led to formation of an amorphous layer below and above the slip plane of the basal dislocations. The kink induced in the precipitate by this mechanism was in good agreement with transmission electron microscopy observations.

Published
2020

11. Mixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling

Author

Hobor, S, Al Bakir, M, Hiley, C, Skrzypski, M, Frankell, A, Bakker, B, Watkins, T, Markovets, A, Dry, J, Brown, A, van der Aart, J, van den Bos, H, Spierings, D, Oukrif, D, Novelli, M, Chakrabarti, T, Rabinowitz, A, Ait Hassou, L, Litiere, S, Kerr, D, Tan, L, Kelly, G, Moore, D, Renshaw, M, Venkatesan, S, Hill, W, Huebner, A, Martinez-Ruiz, C, Black, J, Wu, W, Angelova, M, Mcgranahan, N, Downward, J, Chmielecki, J, Barrett, C, Litchfield, K, Chew, S, Blakely, C, de Bruin, E, Foijer, F, Vousden, K, Bivona, T, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Tufail, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, French, J, Gilbert, K, Naidu, B, Patel, A, Osman, A, Enstone, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totton, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Paiva-Correia, A, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Brown, K, Carter, M, Chaturvedi, A, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Van Loo, P, Birkbak, N, Szallasi, Z, Kisistok, J, Sokac, M, Salgado, R, Diossy, M, Demeulemeester, J, Bunkum, A, Dwornik, A, Magness, A, Rowan, A, Karamani, A, Toncheva, A, Chain, B, Castignani, C, Bailey, C, Abbosh, C, Puttick, C, Weeden, C, Lee, C, Richard, C, Naceur-Lombardelli, C, Pearce, D, Karagianni, D, Biswas, D, Levi, D, Larose Cadieux, E, Lim, E, Colliver, E, Nye, E, Galvez-Cancino, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Noorani, I, Goldman, J, Reading, J, Rane, J, Nicod, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Thol, K, Ng, K, Chen, K, Dijkstra, K, Grigoriadis, K, Thakkar, K, Ensell, L, Shah, M, Litovchenko, M, Jamal-Hanjani, M, Werner Sunderland, M, Huska, M, Hill, M, Dietzen, M, Leung, M, Escudero, M, Tanic, M, Sivakumar, M, Chervova, O, Lucas, O, Pich, O, Al-Sawaf, O, Prymas, P, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Vendramin, R, Saghafinia, S, Gamble, S, Veeriah, S, Ung, S, Quezada, S, Vanloo, S, Hessey, S, Ward, S, Harries, S, Boeing, S, Beck, S, Bola, S, Karasaki, T, Denner, T, Marafioti, T, Jones, T, Spanswick, V, Barbe, V, Lu, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Kaplar, Z, Bandula, S, Hackshaw, A, Hacker, A, Sharp, A, Smith, S, Kaur Dhanda, H, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Richards, J, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Kidd, A, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Hynds, R, Kanu, N, Zaccaria, S, Gronroos, E, Swanton, C, Hobor S., Al Bakir M., Hiley C. T., Skrzypski M., Frankell A. M., Bakker B., Watkins T. B. K., Markovets A., Dry J. R., Brown A. P., van der Aart J., van den Bos H., Spierings D., Oukrif D., Novelli M., Chakrabarti T., Rabinowitz A. H., Ait Hassou L., Litiere S., Kerr D. L., Tan L., Kelly G., Moore D. A., Renshaw M. J., Venkatesan S., Hill W., Huebner A., Martinez-Ruiz C., Black J. R. M., Wu W., Angelova M., McGranahan N., Downward J., Chmielecki J., Barrett C., Litchfield K., Chew S. K., Blakely C. M., de Bruin E. C., Foijer F., Vousden K. H., Bivona T. G., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Tufail M., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., French J., Gilbert K., Naidu B., Patel A. J., Osman A., Enstone C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totton N., Montero A., Smith E., Fontaine E., Granato F., Paiva-Correia A., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P. A. J., Brown K. D., Carter M., Chaturvedi A., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Van Loo P., Birkbak N. J., Szallasi Z., Kisistok J., Sokac M., Salgado R., Diossy M., Demeulemeester J., Bunkum A., Dwornik A., Magness A., Rowan A. J., Karamani A., Toncheva A., Chain B., Castignani C., Bailey C., Abbosh C., Puttick C., Weeden C. E., Lee C., Richard C., Naceur-Lombardelli C., Pearce D. R., Karagianni D., Biswas D., Levi D., Larose Cadieux E., Lim E. L., Colliver E., Nye E., Galvez-Cancino F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G. -T., Lowe H. L., Matos I. G., Noorani I., Goldman J., Reading J. L., Rane J. K., Nicod J., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Thol K., Ng K. W., Chen K., Dijkstra K., Grigoriadis K., Thakkar K., Ensell L., Shah M., Litovchenko M., Jamal-Hanjani M., Werner Sunderland M., Huska M. R., Hill M. S., Dietzen M., Leung M. M., Escudero M., Tanic M., Sivakumar M., Chervova O., Lucas O., Pich O., Al-Sawaf O., Prymas P., Hobson P., Pawlik P., Stone R. K., Bentham R., Vendramin R., Saghafinia S., Gamble S., Veeriah S., Ung S. K. A., Quezada S. A., Vanloo S., Hessey S., Ward S., Harries S., Boeing S., Beck S., Bola S. K., Karasaki T., Denner T., Marafioti T., Jones T. P., Spanswick V., Barbe V., Lu W. -T., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Gorman P., Khiroya R., Stephens R. C. M., Wong Y. N. S., Kaplar Z., Bandula S., Hackshaw A., Hacker A. -M., Sharp A., Smith S., Kaur Dhanda H., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Richards J., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Kidd A., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Hynds R. E., Kanu N., Zaccaria S., Gronroos E., Swanton C., Hobor, S, Al Bakir, M, Hiley, C, Skrzypski, M, Frankell, A, Bakker, B, Watkins, T, Markovets, A, Dry, J, Brown, A, van der Aart, J, van den Bos, H, Spierings, D, Oukrif, D, Novelli, M, Chakrabarti, T, Rabinowitz, A, Ait Hassou, L, Litiere, S, Kerr, D, Tan, L, Kelly, G, Moore, D, Renshaw, M, Venkatesan, S, Hill, W, Huebner, A, Martinez-Ruiz, C, Black, J, Wu, W, Angelova, M, Mcgranahan, N, Downward, J, Chmielecki, J, Barrett, C, Litchfield, K, Chew, S, Blakely, C, de Bruin, E, Foijer, F, Vousden, K, Bivona, T, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Tufail, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, French, J, Gilbert, K, Naidu, B, Patel, A, Osman, A, Enstone, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totton, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Paiva-Correia, A, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Brown, K, Carter, M, Chaturvedi, A, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Van Loo, P, Birkbak, N, Szallasi, Z, Kisistok, J, Sokac, M, Salgado, R, Diossy, M, Demeulemeester, J, Bunkum, A, Dwornik, A, Magness, A, Rowan, A, Karamani, A, Toncheva, A, Chain, B, Castignani, C, Bailey, C, Abbosh, C, Puttick, C, Weeden, C, Lee, C, Richard, C, Naceur-Lombardelli, C, Pearce, D, Karagianni, D, Biswas, D, Levi, D, Larose Cadieux, E, Lim, E, Colliver, E, Nye, E, Galvez-Cancino, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Noorani, I, Goldman, J, Reading, J, Rane, J, Nicod, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Thol, K, Ng, K, Chen, K, Dijkstra, K, Grigoriadis, K, Thakkar, K, Ensell, L, Shah, M, Litovchenko, M, Jamal-Hanjani, M, Werner Sunderland, M, Huska, M, Hill, M, Dietzen, M, Leung, M, Escudero, M, Tanic, M, Sivakumar, M, Chervova, O, Lucas, O, Pich, O, Al-Sawaf, O, Prymas, P, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Vendramin, R, Saghafinia, S, Gamble, S, Veeriah, S, Ung, S, Quezada, S, Vanloo, S, Hessey, S, Ward, S, Harries, S, Boeing, S, Beck, S, Bola, S, Karasaki, T, Denner, T, Marafioti, T, Jones, T, Spanswick, V, Barbe, V, Lu, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Kaplar, Z, Bandula, S, Hackshaw, A, Hacker, A, Sharp, A, Smith, S, Kaur Dhanda, H, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Richards, J, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Kidd, A, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Hynds, R, Kanu, N, Zaccaria, S, Gronroos, E, Swanton, C, Hobor S., Al Bakir M., Hiley C. T., Skrzypski M., Frankell A. M., Bakker B., Watkins T. B. K., Markovets A., Dry J. R., Brown A. P., van der Aart J., van den Bos H., Spierings D., Oukrif D., Novelli M., Chakrabarti T., Rabinowitz A. H., Ait Hassou L., Litiere S., Kerr D. L., Tan L., Kelly G., Moore D. A., Renshaw M. J., Venkatesan S., Hill W., Huebner A., Martinez-Ruiz C., Black J. R. M., Wu W., Angelova M., McGranahan N., Downward J., Chmielecki J., Barrett C., Litchfield K., Chew S. K., Blakely C. M., de Bruin E. C., Foijer F., Vousden K. H., Bivona T. G., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Tufail M., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., French J., Gilbert K., Naidu B., Patel A. J., Osman A., Enstone C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totton N., Montero A., Smith E., Fontaine E., Granato F., Paiva-Correia A., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P. A. J., Brown K. D., Carter M., Chaturvedi A., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Van Loo P., Birkbak N. J., Szallasi Z., Kisistok J., Sokac M., Salgado R., Diossy M., Demeulemeester J., Bunkum A., Dwornik A., Magness A., Rowan A. J., Karamani A., Toncheva A., Chain B., Castignani C., Bailey C., Abbosh C., Puttick C., Weeden C. E., Lee C., Richard C., Naceur-Lombardelli C., Pearce D. R., Karagianni D., Biswas D., Levi D., Larose Cadieux E., Lim E. L., Colliver E., Nye E., Galvez-Cancino F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G. -T., Lowe H. L., Matos I. G., Noorani I., Goldman J., Reading J. L., Rane J. K., Nicod J., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Thol K., Ng K. W., Chen K., Dijkstra K., Grigoriadis K., Thakkar K., Ensell L., Shah M., Litovchenko M., Jamal-Hanjani M., Werner Sunderland M., Huska M. R., Hill M. S., Dietzen M., Leung M. M., Escudero M., Tanic M., Sivakumar M., Chervova O., Lucas O., Pich O., Al-Sawaf O., Prymas P., Hobson P., Pawlik P., Stone R. K., Bentham R., Vendramin R., Saghafinia S., Gamble S., Veeriah S., Ung S. K. A., Quezada S. A., Vanloo S., Hessey S., Ward S., Harries S., Boeing S., Beck S., Bola S. K., Karasaki T., Denner T., Marafioti T., Jones T. P., Spanswick V., Barbe V., Lu W. -T., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Gorman P., Khiroya R., Stephens R. C. M., Wong Y. N. S., Kaplar Z., Bandula S., Hackshaw A., Hacker A. -M., Sharp A., Smith S., Kaur Dhanda H., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Richards J., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Kidd A., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Hynds R. E., Kanu N., Zaccaria S., Gronroos E., and Swanton C.

Abstract

The phenomenon of mixed/heterogenous treatment responses to cancer therapies within an individual patient presents a challenging clinical scenario. Furthermore, the molecular basis of mixed intra-patient tumor responses remains unclear. Here, we show that patients with metastatic lung adenocarcinoma harbouring co-mutations of EGFR and TP53, are more likely to have mixed intra-patient tumor responses to EGFR tyrosine kinase inhibition (TKI), compared to those with an EGFR mutation alone. The combined presence of whole genome doubling (WGD) and TP53 co-mutations leads to increased genome instability and genomic copy number aberrations in genes implicated in EGFR TKI resistance. Using mouse models and an in vitro isogenic p53-mutant model system, we provide evidence that WGD provides diverse routes to drug resistance by increasing the probability of acquiring copy-number gains or losses relative to non-WGD cells. These data provide a molecular basis for mixed tumor responses to targeted therapy, within an individual patient, with implications for therapeutic strategies.

Published
2024

18. Clinical and genomic landscape of RAS mutations in gynecologic cancers

Author

Son, Ji, primary, Zhang, Yingao, additional, Lin, Heather, additional, Mirallas, Oriol, additional, Alvarez Ballesteros, Pablo, additional, Nardo, Mirella, additional, Clark, Natalie, additional, Hillman, R. Tyler, additional, Campbell, Erick, additional, Holla, Vijaykumar, additional, Johnson, Amber M., additional, Biter, Amadeo B., additional, Yuan, Ying, additional, Cobb, Lauren P., additional, Gershenson, David M., additional, Jazaeri, Amir A., additional, Lu, Karen H., additional, Soliman, Pamela T., additional, Westin, Shannon N., additional, Euscher, Elizabeth D., additional, Lawson, Barrett C., additional, Yang, Richard K., additional, Meric-Bernstam, Funda, additional, and Hong, David S., additional

Published
2024
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22. Molecular, Metabolic, and Subcellular Mapping of the Tumor Immune Microenvironment via 3D Targeted and Non-Targeted Multiplex Multi-Omics Analyses

Author

Ferri-Borgogno, Sammy, primary, Burks, Jared K., additional, Seeley, Erin H., additional, McKee, Trevor D., additional, Stolley, Danielle L., additional, Basi, Akshay V., additional, Gomez, Javier A., additional, Gamal, Basant T., additional, Ayyadhury, Shamini, additional, Lawson, Barrett C., additional, Yates, Melinda S., additional, Birrer, Michael J., additional, Lu, Karen H., additional, and Mok, Samuel C., additional

Published
2024
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23. Guidance for the gastrointestinal evaluation and management of iron deficiency in Sub-Saharan Africa

Author

Simmonds, W M, primary, Awuku, Y, additional, Barrett, C, additional, Brand, M, additional, Davidson, K, additional, Epstein, D, additional, Fredericks, E, additional, Gabriel, S, additional, Grobler, S, additional, Gounden, C, additional, Katsidzira, L, additional, Louw, V J, additional, Naidoo, V, additional, Noel, C, additional, Ogutu, E, additional, Ramonate, N, additional, Seabi, N, additional, Setshedi, M, additional, Van Zyl, J, additional, Watermeyer, G, additional, and Kassianides, C, additional

Published
2024
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26. Association between night-time surgery and occurrence of intraoperative adverse events and postoperative pulmonary complications

Author

Kroell, W., Metzler, H., Struber, G., Wegscheider, T., Gombotz, H., Hiesmayr, M., Schmid, W., Urbanek, B., Kahn, D., Momeni, M., Pospiech, A., Lois, F., Forget, P., Grosu, I., Poelaert, J., Mossevelde, V., van Malderen, M.C., Dylst, D., Melkebeek, J.V., Beran, M., Hert, S.D., Baerdemaeker, L.D., Heyse, B., Limmen, J.V., Wyffels, P., Jacobs, T., Roels, N., Bruyne, A.D., Velde, S.V.D., Marina, J.Z., Dejana, D.O., Pernar, S., Zunic, J., Miskovic, P., Zilic, A., Kvolik, S., Ivic, D., Darija, A.V., Skiljic, S., Vinkovic, H., Oputric, I., Juricic, K., Frkovic, V., Kopic, J., Mirkovic, I., Saric, J.P., Erceg, G., Dvorscak, M.B., Branka, M.S., Pavicic, A.M., Goranovic, T., Maldini, B., Radocaj, T., Gavranovic, Z., Inga, M.B., Sehovic, M., Stourac, P., Harazim, H., Smekalova, O., Kosinova, M., Kolacek, T., Hudacek, K., Drab, M., Brujevic, J., Vitkova, K., Jirmanova, K., Volfova, I., Dzurnakova, P., Liskova, K., Dudas, R., Filipsky, R., Kafrawy, S.E., Abdelwahab, H.H., Metwally, T., Ahmed, A.R., Ahmed Mostafa, E.S., Hasan, W.F., Ahmed, A.G., Yassin, H., Magdy, M., Abdelhady, M., Mahran, M., Herodes, E., Kivik, P., Oganjan, J., Aun, A., Sormus, A., Sarapuu, K., Mall, M., Karjagin, J., Futier, E., Petit, A., Gerard, A., Marret, E., Solier, M., Jaber, S., Prades, A., Krassler, J., Merzky, S., Abreu, M.G.D., Uhlig, C., Kiss, T., Bundy, A., Bluth, T., Gueldner, A., Spieth, P., Scharffenberg, M., Thiem, D.T., Koch, T., Treschan, T., Schaefer, M., Bastin, B., Geib, J., Weiss, M., Kienbaum, P., Pannen, B., Gottschalk, A., Konrad, M., Westerheide, D., Schwerdtfeger, B., Wrigge, H., Simon, P., Reske, A., Nestler, C., Valsamidis, D., Stroumpoulis, K., Antholopoulos, G., Andreou, A., Karapanos, D., Theodoraki, K., Gkiokas, G., Tasoulis, M.K., Sidiropoulou, T., Zafeiropoulou, F., Florou, P., Pandazi, A., Tsaousi, G., Nouris, C., Pourzitaki, C., Bystritski, D., Pizov, R., Eden, A., Pesce, C.V., Campanile, A., Marrella, A., Grasso, S., Michele, M.D., Bona, F., Giacoletto, G., Sardo, E., Sottosanti, L.G.V., Solca, M., Volta, C.A., Spadaro, S., Verri, M., Ragazzi, R., Zoppellari, R., Cinnella, G., Raimondo, P., Bella, D.L., Mirabella, L., D'antini, D., Pelosi, P., Molin, A., Brunetti, I., Gratarola, A., Pellerano, G., Sileo, R., Pezzatto, S., Montagnani, L., Pasin, L., Landoni, G., Zangrillo, A., Beretta, L., Parma, A.L.D., Tarzia, V., Dossi, R., Sassone, M.E., Sances, D., Tredici, S., Spano, G., Castellani, G., Delunas, L., Peradze, S., Venturino, M., Arpino, I., Sher, S., Tommasino, C., Rapido, F., Morelli, P., Vargas, M., Servillo, G., Cortegiani, A., Raineri, S.M., Montalto, F., Russotto, V., Giarratano, A., Baciarello, M., Generali, M., Cerati, G., Leykin, Y., Bressan, F., Bartolini, V., Zamidei, L., Brazzi, L., Liperi, C., Sales, G., Pistidda, L., Severgnini, P., Brugnoni, E., Musella, G., Bacuzzi, A., Muhardri, D., Agreta, G.G., Sada, F., Bytyqi, A., Karbonskiene, A., Aukstakalniene, R., Teberaite, Z., Salciute, E., Tikuisis, R., Miliauskas, P., Jurate, S., Kontrimaviciute, E., Tomkute, G., Xuereb, J., Bezzina, M., Borg, F. Joseph, Hemmes, S., Schultz, M., Hollmann, M., Wiersma, I., Binnekade, J., Bos, L., Boer, C., Duvekot, A., Veld, B.I ‘t, Werger, A., Dennesen, P., Severijns, C., Jong, J.D., Hering, J., Beek, R.V., Ivars, S., Jammer, I.B., Breidablik, A., Hodt, K.S., Fjellanger, F., Avalos, M.V., Jannicke, M.O., Andersson, E., Amir, S.K., Molina, R., Wutai, S., Morais, E., Tareco, G., Ferreira, D., Amaral, J., Castro, M.D.L.G., Cadilha, S., Appleton, S., Parente, S., Correia, M., Martins, D., Monteirosa, A., Ricardo, A., Rodrigues, S., Horhota, L., Grintescu, I.M., Mirea, L., Grintescu, I.C., Corneci, D., Negoita, S., Dutu, M., Popescu Garotescu, I., Filipescu, D., Prodan, A.B., Droc, G., Fota, R., Popescu, M., Tomescu, D., Petcu, A.M., Tudoroiu, M.I., Moise, A., Guran, C.T., Gherghina, I., Costea, D., Cindea, I., Copotoiu, S.M., Copotoiu, R., Barsan, V., Tolcser, Z., Riciu, M., Moldovan, S.G., Veres, M., Gritsan, A., Kapkan, T., Gritsan, G., Korolkov, O., Kulikov, A., Lubnin, A., Ovezov, A., Prokoshev, P., Lugovoy, A., Anipchenko, N., Babayants, A., Komissarova, I., Zalina, K., Likhvantsev, V., Fedorov, S., Lazukic, A., Pejakovic, J., Mihajlovic, D., Kusnierikova, Z., Zelinkova, M., Bruncakova, K., Polakovicova, L., Sobona, V., Barbka, N.S., Ana, P.G., Jovanov, M., Strazisar, B., Jasmina, M.B., Vesna, N.J., Voje, M., Grynyuk, A., Kostadinov, I., Alenka, S.V., Moral, V., Unzueta, M.C., Puigbo, C., Fava, J., Canet, J., Moret, E., Nunez, M.R., Sendra, M., Brunelli, A., Rodenas, F., Monedero, P., Hidalgo, F., Yepes, M.J., Martinez-Simon, A., Abajo, A., Lisi, A., Perez, G., Martinez, R., Granell, M., Vivo, J.T., Ruiz, C.S., Andrés Ibañez, J.A.D., Pastor, E., Soro, M., Ferrando, C., Defez, M., Cesar Aldecoa, A.S., Perez, R., Rico, J., Jawad, M., Saeed, Y., Gillberg, L., Bengisun, Z.K., Kazbek, B.K., Coskunfirat, N., Boztug, N., Sanli, S., Yilmaz, M., Hadimioglu, N., Senturk, N.M., Camci, E., Kucukgoncu, S., Sungur, Z., Sivrikoz, N., Ozgen, S.U., Toraman, F., Selvi, O., Senturk, O., Yildiz, M., Kuvaki, B., Gunenc, F., Kucukguclu, S., Ozbilgin, S., Maral, J., Canli, S., Arun, O., Saltali, A., Aydogan, E., Akgun, F.N., Sanlikarip, C., Karaman, F.M., Mazur, A., Vorotyntsev, S., Rousseau, G., Barrett, C., Stancombe, L., Shelley, B., Scholes, H., Limb, J., Rafi, A., Wayman, L., Deane, J., Rogerson, D., Williams, J., Yates, S., Rogers, E., Pulletz, M., Moreton, S., Jones, S., Venkatesh, S., Burton, M., Brown, L., Goodall, C., Rucklidge, M., Fuller, D., Nadolski, M., Kusre, S., Lundberg, M., Everett, L., Nutt, H., Zuleika, M., Carvalho, P., Clements, D., Ben, C.B., Watt, P., Raymode, P., Pearse, R., Mohr, O., Raj, A., Creary, T., Chishti, A., Bell, A., Higham, C., Cain, A., Gibb, S., Mowat, S., Franklin, D., West, C., Minto, G., Boyd, N., Mills, G., Calton, E., Walker, R., Mackenzie, F., Ellison, B., Roberts, H., Chikungwa, M., Jackson, C., Donovan, A., Foot, J., Homan, E., Montgomery, J., Portch, D., Mercer, P., Palmer, J., Paddle, J., Fouracres, A., Datson, A., Andrew, A., Welch, L., Rose, A., Varma, S., Simeson, K., Rambhatla, M., Susarla, J., Marri, S., Kodaganallur, K., Das, A., Algarsamy, S., Colley, J., Davies, S., Szewczyk, M., Smith, T., Ana, F.B., Luzier, E., Almagro, A., Melo, M.V., Fernando, L., Sulemanji, D., Sprung, J., Weingarten, T., Kor, D., Scavonetto, F., Tze, Y., Gregoretti, C., Neto, A.S., Hemmes, S.N.T., Ball, L., Hollmann, M.W., Mills, G.H., Melo, M.F.V., Putensen, C., Gama de Abreu, M., and Schultz, M.J.

Published
2019
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28. Transforming ovarian cancer care by targeting minimal residual disease

Author

Jazaeri, Amir A., primary, Grisham, Rachel, additional, Knisely, Anne, additional, Spranger, Stefani, additional, Zamarin, Dmitriy, additional, Hillman, R. Tyler, additional, Lawson, Barrett C., additional, Burns, Kathleen H., additional, Lee, Sanghoon, additional, Westin, Shannon N., additional, Moiso, Enrico, additional, Williams, Marc J., additional, Bardhan, Neelkanth M., additional, Pisanic, Thomas, additional, Matulonis, Ursula, additional, Weigelt, Britta, additional, Shih, IeMing, additional, Konstantinopoulos, Panagiotis A., additional, Gaillard, Stephanie, additional, Wang, Linghua, additional, Aghajanian, Carol, additional, D’Andrea, Alan D., additional, Hammond, Paula, additional, Shah, Sohrab, additional, Wucherpfennig, Kai W., additional, and Lu, Karen H., additional

Published
2023
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29. The Role of a Registered Dietitian Nutritionist in Improving Weight Loss Prior to Elective Total Joint Arthroplasty in Overweight or Obese Adults Among Participants in MODIFY, a Pre-surgical Optimization Program

Author

Quigley, T., primary, Kostyun, R., additional, Barrett, C., additional, McCracken, C., additional, Bosco, B., additional, Kosma, K., additional, Perez, C., additional, Kumar, M., additional, Shanley, E., additional, and Wanik, J., additional

Published
2023
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30. Planar Atom Trap and Magnetic Resonance 'Lens' Designs

Author

Barbic, M., Barrett, C. P., Emery, T. H., and Scherer, A.

Subjects
Physics - Atomic Physics, Physics - Medical Physics
Abstract

We present various planar magnetic designs that create points above the plane where the magnitude of the static magnetic field is a local minimum. Structures with these properties are of interest in the disciplines of neutral atom confinement, magnetic levitation, and magnetic resonance imaging. Each planar permanent magnet design is accompanied by the equivalent planar single non-crossing conductor design. Presented designs fall into three categories producing: a) zero value magnetic field magnitude point minima, b) non-zero magnetic field magnitude point minima requiring external bias magnetic field, and c) self-biased non-zero magnetic field magnitude point minima. We also introduce the Principle of Amperean Current Doubling in planar perpendicularly magnetized thin films that can be used to improve the performance of each permanent magnet design we present. Single conductor current-carrying designs are suitable for single layer lithographic fabrication, as we experimentally demonstrate. Finally, we present the case that nanometer scale recording of perpendicular anisotropy thin magnetic films using presently available data storage technology can provide the ultimate miniaturization of the presented designs., Comment: 19 text pages, 8 figures

Published
2007

31. Extrauterine Mesonephric-like Carcinoma

Author

Elizabeth D. Euscher, Mario L. Marques-Piubelli, Preetha Ramalingam, Ignacio Wistuba, Barrett C. Lawson, Michael Frumovitz, and Anais Malpica

Subjects
Surgery, Anatomy, Pathology and Forensic Medicine
Published
2023

32. Micro-foundations of organizational knowledge sharing

Author

Kou-Barrett, C.

Subjects
658
Abstract

Although current research on knowledge sharing has offered significant insights into the effective exchange of expert knowledge in day-to-day assignments, the role of individuals within these knowledge sharing processes, as well as how they affect individuals’ subsequent knowledge sharing choices, remains relatively under-explored. This dissertation investigates the role of individuals in knowledge coordination processes through three grounded, qualitative studies based on large engineering projects in a multi-national engineering consultation and information technology company. Study 1 focuses on the evolution of task interdependence during knowledge coordination and examines how a group of individuals become collectively responsible for problems that arise during work interactions. The process model shows that individuals re-interpret their accountability depending on the nature of the problem at hand, which, in turn, influences their subsequent problem solving efforts. Study 2 explores how managers shape the team’s interdependence . This study shows that task interdependence can be developed and reciprocally reinforced through knowledge creation, even in spite of physical distances. The model shows that the use of boundary objects – templates – not only alters focus at both team and project level but also effectively integrates and aligns discrete team efforts toward a unified project goal. Study 3 sets out to explore how interdependence is affected by distance, focusing on the development of psychological inter-team interdependence through comparison of two projects. In particular, the emergent model of inter-team closeness revolves around sensemaking of cross-team distance and of one’s own role. As such, findings reveal that distributed teams may actually have higher levels of inter-team closeness than collocated teams.

Published
2013

35. Quality of life in patients with advanced epithelial ovarian cancer (EOC) randomized to maintenance pazopanib or placebo after first-line chemotherapy in the AGO-OVAR 16 trial. Measuring what matters—patient-centered end points in trials of maintenance therapy

Author

Friedlander, M., Rau, J., Lee, C.K., Meier, W., Lesoin, A., Kim, J.-W., Poveda, A., Buck, M., Scambia, G., Shimada, M., Hilpert, F., King, M.T., Debruyne, P., Bologna, A., Malander, S., Monk, B.J., Petru, E., Calvert, P., Herzog, T.J., Barrett, C., and du Bois, A.

Published
2018
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39. The relationship between uremic toxins and symptoms in older men and women with advanced chronic kidney disease

Author

Massy Z. A., Chesnaye N. C., Larabi I. A., Dekker F. W., Evans M., Caskey F. J., Torino C., Porto G., Szymczak M., Drechsler C., Wanner C., Jager K. J., Alvarez J. C., Schneider A., Torp A., Iwig B., Perras B., Marx C., Blaser C., Emde C., Krieter D., Fuchs D., Irmler E., Platen E., Schmidt-Gurtler H., Schlee H., Naujoks H., Schlee I., Casar S., Beige J., Rothele J., Mazur J., Hahn K., Blouin K., Neumeier K., Anding-Rost K., Schramm L., Hopf M., Wuttke N., Frischmuth N., Ichtiaris P., Kirste P., Schulz P., Aign S., Biribauer S., Manan S., Roser S., Heidenreich S., Palm S., Schwedler S., Delrieux S., Renker S., Schattel S., Stephan T., Schmiedeke T., Weinreich T., Leimbach T., Stovesand T., Bahner U., Seeger W., Cupisti A., Sagliocca A., Ferraro A., Mele A., Naticchia A., Cosaro A., Ranghino A., Stucchi A., Pignataro A., De Blasio A., Pani A., Tsalouichos A., Bellasi A., Raffaele Di Iorio B., Butti A., Abaterusso C., Somma C., D'Alessandro C., Zullo C., Pozzi C., Bergamo D., Ciurlino D., Motta D., Russo D., Favaro E., Vigotti F., Ansali F., Conte F., Cianciotta F., Giacchino F., Cappellaio F., Pizzarelli F., Greco G., Bigatti G., Marinangeli G., Cabiddu G., Fumagalli G., Caloro G., Piccoli G., Capasso G., Gambaro G., Tognarelli G., Bonforte G., Conte G., Toscano G., Del Rosso G., Capizzi I., Baragetti I., Oldrizzi L., Gesualdo L., Biancone L., Magnano M., Ricardi M., Di Bari M., Laudato M., Luisa Sirico M., Ferraresi M., Provenzano M., Malaguti M., Palmieri N., Murrone P., Cirillo P., Dattolo P., Acampora P., Nigro R., Boero R., Scarpioni R., Sicoli R., Malandra R., Savoldi S., Bertoli S., Borrelli S., Maxia S., Maffei S., Mangano S., Cicchetti T., Rappa T., Palazzo V., De Simone W., Schrander A., Van Dam B., Siegert C., Gaillard C., Beerenhout C., Verburgh C., Janmaat C., Hoogeveen E., Hoorn E., Boots J., Boom H., Eijgenraam J. -W., Kooman J., Rotmans J., Vogt L., Raasveld M., Vervloet M., Van Buren M., Van Diepen M., Leurs P., Voskamp P., Blankestijn P., Van Esch S., Boorsma S., Berger S., Konings C., Aydin Z., Musiala A., Szymczak A., Olczyk E., Augustyniak-Bartosik H., Miskowiec-Wisniewska I., Manitius J., Pondel J., Jedrzejak K., Nowanska K., Nowak L., Durlik M., Dorota S., Nieszporek T., Heleniak Z., Jonsson A., Blom A. -L., Rogland B., Wallquist C., Vargas D., Dimeny E., Sundelin F., Uhlin F., Welander G., Bascaran Hernandez I., Grontoft K. -C., Stendahl M., Svensson M., Heimburger O., Kashioulis P., Melander S., Almquist T., Jensen U., Woodman A., McKeever A., Ullah A., McLaren B., Harron C., Barrett C., O'Toole C., Summersgill C., Geddes C., Glowski D., McGlynn D., Sands D., Roy G., Hirst G., King H., McNally H., Masri-Senghor H., Murtagh H., Rayner H., Turner J., Wilcox J., Berdeprado J., Wong J., Banda J., Jones K., Haydock L., Wilkinson L., Carmody M., Weetman M., Joinson M., Dutton M., Matthews M., Morgan N., Bleakley N., Cockwell P., Roderick P., Mason P., Kalra P., Sajith R., Chapman S., Navjee S., Crosbie S., Brown S., Tickle S., Mathavakkannan S., Kuan Y., Massy, Z. A., Chesnaye, N. C., Larabi, I. A., Dekker, F. W., Evans, M., Caskey, F. J., Torino, C., Porto, G., Szymczak, M., Drechsler, C., Wanner, C., Jager, K. J., Alvarez, J. C., Schneider, A., Torp, A., Iwig, B., Perras, B., Marx, C., Blaser, C., Emde, C., Krieter, D., Fuchs, D., Irmler, E., Platen, E., Schmidt-Gurtler, H., Schlee, H., Naujoks, H., Schlee, I., Casar, S., Beige, J., Rothele, J., Mazur, J., Hahn, K., Blouin, K., Neumeier, K., Anding-Rost, K., Schramm, L., Hopf, M., Wuttke, N., Frischmuth, N., Ichtiaris, P., Kirste, P., Schulz, P., Aign, S., Biribauer, S., Manan, S., Roser, S., Heidenreich, S., Palm, S., Schwedler, S., Delrieux, S., Renker, S., Schattel, S., Stephan, T., Schmiedeke, T., Weinreich, T., Leimbach, T., Stovesand, T., Bahner, U., Seeger, W., Cupisti, A., Sagliocca, A., Ferraro, A., Mele, A., Naticchia, A., Cosaro, A., Ranghino, A., Stucchi, A., Pignataro, A., De Blasio, A., Pani, A., Tsalouichos, A., Bellasi, A., Raffaele Di Iorio, B., Butti, A., Abaterusso, C., Somma, C., D'Alessandro, C., Zullo, C., Pozzi, C., Bergamo, D., Ciurlino, D., Motta, D., Russo, D., Favaro, E., Vigotti, F., Ansali, F., Conte, F., Cianciotta, F., Giacchino, F., Cappellaio, F., Pizzarelli, F., Greco, G., Bigatti, G., Marinangeli, G., Cabiddu, G., Fumagalli, G., Caloro, G., Piccoli, G., Capasso, G., Gambaro, G., Tognarelli, G., Bonforte, G., Conte, G., Toscano, G., Del Rosso, G., Capizzi, I., Baragetti, I., Oldrizzi, L., Gesualdo, L., Biancone, L., Magnano, M., Ricardi, M., Di Bari, M., Laudato, M., Luisa Sirico, M., Ferraresi, M., Provenzano, M., Malaguti, M., Palmieri, N., Murrone, P., Cirillo, P., Dattolo, P., Acampora, P., Nigro, R., Boero, R., Scarpioni, R., Sicoli, R., Malandra, R., Savoldi, S., Bertoli, S., Borrelli, S., Maxia, S., Maffei, S., Mangano, S., Cicchetti, T., Rappa, T., Palazzo, V., De Simone, W., Schrander, A., Van Dam, B., Siegert, C., Gaillard, C., Beerenhout, C., Verburgh, C., Janmaat, C., Hoogeveen, E., Hoorn, E., Boots, J., Boom, H., Eijgenraam, J. -W., Kooman, J., Rotmans, J., Vogt, L., Raasveld, M., Vervloet, M., Van Buren, M., Van Diepen, M., Leurs, P., Voskamp, P., Blankestijn, P., Van Esch, S., Boorsma, S., Berger, S., Konings, C., Aydin, Z., Musiala, A., Szymczak, A., Olczyk, E., Augustyniak-Bartosik, H., Miskowiec-Wisniewska, I., Manitius, J., Pondel, J., Jedrzejak, K., Nowanska, K., Nowak, L., Durlik, M., Dorota, S., Nieszporek, T., Heleniak, Z., Jonsson, A., Blom, A. -L., Rogland, B., Wallquist, C., Vargas, D., Dimeny, E., Sundelin, F., Uhlin, F., Welander, G., Bascaran Hernandez, I., Grontoft, K. -C., Stendahl, M., Svensson, M., Heimburger, O., Kashioulis, P., Melander, S., Almquist, T., Jensen, U., Woodman, A., Mckeever, A., Ullah, A., Mclaren, B., Harron, C., Barrett, C., O'Toole, C., Summersgill, C., Geddes, C., Glowski, D., Mcglynn, D., Sands, D., Roy, G., Hirst, G., King, H., Mcnally, H., Masri-Senghor, H., Murtagh, H., Rayner, H., Turner, J., Wilcox, J., Berdeprado, J., Wong, J., Banda, J., Jones, K., Haydock, L., Wilkinson, L., Carmody, M., Weetman, M., Joinson, M., Dutton, M., Matthews, M., Morgan, N., Bleakley, N., Cockwell, P., Roderick, P., Mason, P., Kalra, P., Sajith, R., Chapman, S., Navjee, S., Crosbie, S., Brown, S., Tickle, S., Mathavakkannan, S., Kuan, Y., Nephrology, ACS - Diabetes & metabolism, Medical Informatics, APH - Methodology, APH - Aging & Later Life, APH - Quality of Care, APH - Global Health, APH - Health Behaviors & Chronic Diseases, and ACS - Pulmonary hypertension & thrombosis

Subjects
Transplantation, Nephrology, uremic toxins, CKD, symptoms, symptom, elderly
Abstract

Background Patients with stage 4/5 chronic kidney disease (CKD) suffer from various symptoms. The retention of uremic solutes is thought to be associated with those symptoms. However, there are relatively few rigorous studies on the potential links between uremic toxins and symptoms in patients with CKD. Methods The EQUAL study is an ongoing observational cohort study of non-dialyzed patients with stage 4/5 CKD. EQUAL patients from Germany, Poland, Sweden and the UK were included in the present study (n = 795). Data and symptom self-report questionnaires were collected between April 2012 and September 2020. Baseline uric acid and parathyroid hormone and 10 uremic toxins were quantified. We tested the association between uremic toxins and symptoms and adjusted P-values for multiple testing. Results Symptoms were more frequent in women than in men with stage 4/5 CKD, while levels of various uremic toxins were higher in men. Only trimethylamine N-oxide (TMAO; positive association with fatigue), p-cresyl sulfate (PCS) with constipation and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (negative association with shortness of breath) demonstrated moderately strong associations with symptoms in adjusted analyses. The association of phenylacetylglutamine with shortness of breath was consistent in both sexes, although it only reached statistical significance in the full population. In contrast, TMAO (fatigue) and PCS and phenylacetylglutamine (constipation) were only associated with symptoms in men, who presented higher serum levels than women. Conclusion Only a limited number of toxins were associated with symptoms in persons with stage 4/5 CKD. Other uremic toxins, uremia-related factors or psychosocial factors not yet explored might contribute to symptom burden.

Published
2022

42. Precursors in the ovarian stroma: another pathway to explain the origin of ovarian serous neoplasms

Author

Elvio G. Silva, Barrett C. Lawson, Preetha Ramalingam, Jinsong Liu, Ahmed Shehabeldin, Mario L. Marques-Piubelli, and Anais Malpica

Subjects
Ovarian Neoplasms, Polyploidy, Cysts, Fallopian Tube Neoplasms, Humans, Female, Peritoneal Neoplasms, Cystadenocarcinoma, Serous, Pathology and Forensic Medicine
Abstract

Ovarian serous neoplasms are thought to arise from the fallopian tube or from the ovarian surface epithelium. The possibility of a third pathway-involving the mesenchymal-epithelial transition and mimicking the formation of the Müllerian duct-arose from observations gathered from our routine cases. The purpose of this study is to determine the association of precursors in the ovarian stroma with different types of ovarian serous neoplasms. Three hundred neoplasms, benign (25), borderline (63), and malignant ovarian serous neoplasms (40 low-grade serous carcinomas [LGSCas] and 172 high-grade serous carcinomas [HGSCas]), were reviewed. Clinicopathologic features analyzed included patient's age, tumor size, stage, histologic pattern, and possible precursors in the ovarian parenchyma (endosalpingiosis, inverted macropapillae, polyploid giant cancer cells, and simple cysts). All benign and borderline cases showed continuity with benign serous cysts or endosalpingiosis. In LGSCas, continuity with serous cysts was found in 29 (72%) of 40 cases, and inverted macropapillae were found in 12 (30%) of 40 cases. In untreated HGSCas, there was continuity with simple cysts in 42% of cases. In addition, these HGSCas contained polyploid giant cancer cells in 20% of cases. There were no different features in the ovaries in cases with or without serous tubal intraepithelial carcinoma. Our study shows that in a subset of cases, ovarian serous neoplasms and the Müllerian duct develop in similar fashion, originating from epithelial cells derived from the mesothelium, or occur de novo from structures derived from mesenchymal-epithelial transition.

Published
2022

47. Management of chronic rheumatic diseases in women 18-45 years of age in Asia Pacific: insights from patient and clinician surveys.

Author

Tanaka, Y, Barrett, C, Hirano, Y, Ikeda, K, Paizis, K, Sameshima, A, Mountian, I, Wong, PC, Tanaka, Y, Barrett, C, Hirano, Y, Ikeda, K, Paizis, K, Sameshima, A, Mountian, I, and Wong, PC

Abstract

OBJECTIVE: Perspectives of women aged 18-45 years with chronic rheumatic diseases (CRD), and clinicians, in the Asia-Pacific (APAC) region are reported. METHODS: Online surveys were completed by women, pregnant in the past 2-5 years, with moderate to severe rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (axSpA), and rheumatologists, obstetricians, orthopaedic surgeons who medically manage CRDs. RESULTS: Among 210 (RA 122, PsA 48, axSpA 40) patients, 52% (n = 109/210) delayed their decision to have children, most commonly due to concerns of passing on disease to offspring. 33% (n = 70/210) discussed family planning with a healthcare professional at diagnosis. Patients most often initiated discussions. 94% (n = 193/205) stopped treatment around pregnancy due to fear of fetal harm. 66% (n = 139/210) of patients felt they did not receive all relevant information on the impact of CRDs and treatment on pregnancy. Among 335 clinicians who participated, 82% (n = 143/174) of rheumatologists, 86% (n = 72/84) of obstetricians and 43% (n = 33/77) of orthopaedic surgeons agreed good disease control during pregnancy was their primary goal. 69% (n = 120/174) of rheumatologists were 'very comfortable' with prescribing tumour necrosis factor inhibitors (TNFi) for women aged 18-45 years. Comfort levels generally decreased with the onset of family planning. More obstetricians and orthopaedic surgeons supported avoiding TNFi during pregnancy than rheumatologists (40% [n = 34/84]/38% [n = 29/77] versus 16% [n = 28/174]). Access to more TNFi safety data during pregnancy was considered paramount for increasing clinician comfort. CONCLUSIONS: Patients and physicians need current information and multidisciplinary discussions for improved management of CRD in women in APAC.

Published
2023

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