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490 results on '"Nugent K"'

10. Acute Gastrointestinal and Genitourinary Toxicity Results from a Prospective Randomized Phase II Trial Evaluating Adjuvant Pelvic Radiotherapy Using Either IMRT or 3-Dimensional Planning for Endometrial Cancer

Author

Nugent, K., primary, Browne, D., additional, Dunne, M., additional, Osullivan, L., additional, Shannon, A.M., additional, Sharma, D., additional, Bradshaw, S., additional, McArdle, O., additional, Salib, O., additional, Lavan, N., additional, and Gillham, C., additional

Published
2023
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11. International Consensus Definition of Low Anterior Resection Syndrome

Author

Keane, Celia, Fearnhead, Nicola S., Bordeianou, Liliana G., Christensen, Peter, Basany, Eloy Espin, Laurberg, Søren, Mellgren, Anders, Messick, Craig, Orangio, Guy R., Verjee, Azmina, Wing, Kirsty, Bissett, Ian, An, V, Bryant, A, Byrne, C, Chen, T, Croft, S, Clark, D, Gladman, M, Heriot, A, Kariappa, S, Keck, J, Lubowski, D, Dinning, P, Khera, A, Kirkwood, K, Petersen, D, Sloots, K, Totten, B, Weston, M, Andersen, P, Bachmann, C, Barht, H, Emmertsen, K, Faaborg, P, Gögenur, I, Ingerslev, P, Isaksen, D, Iversen, H, Iversen, L, Jacobsen, K, Jansen, T, Jocobsen, I, Juul, T, Kjar, D, Krogh, K, Majgaard, M, Mynster, A, Neuenschwander, A, Nielsen, C, Nielsen, R, Nielsen, M, Nielsen, T, Olsen, J, Poulsen, B, Rahr, H, Snedker, B, Sørensen, G, Stolzenburg, T, Vaabengaard, P, Acheson, A, Andreyev, J, Bach, S, Battersby, N, Bradbury, J, Brown, S, Cecil, T, Chapman, S, Chapman, M, Chave, H, Cook, T, Cuffy, L, Davies, J, Dawson, C, Dixon, J, Duff, S, Edwards, C, Geh, I, Hamilton, C, Hancock, L, Harji, D, Hill, J, Holtham, S, Jenkins, J, Johnston, R, Kapur, S, Maxwell-Armstrong, C, McArthur, D, Moran, B, Norton, C, Nugent, K, Pateman, L, Perston, Y, Rockall, T, Sagar, P, Saunders, M, Sebag-Montefiore, D, Senapati, A, Singh, B, Skaife, P, Sykes, H, Smart, N, Taylor, C, Thorpe, G, Tierney, G, Voyce, S, Walsh, C, Warren, O, Wheeler, J, Woodward, A, Winter, D, Abbott, S, Beban, V, Bennett, M, Chadwick, T, Collinson, R, Corbett, S, Dennett, E, Eglinton, T, Fraser, A, Glue, J, Hohaia, D, Menzi, E, O’Connor, M, Stevenson, D, Wells, C, Wolyncewicz, S, Woodfield, J, Bence, K, Boutros, M, Brueseke, M, DeKorte, J, Floruta, C, Francone, T, Frederick, F, Grasso, J, Gurland, B, Higgins, K, Hull, T, Keller, D, Laffan, A, Lovett, S, Marlatt, J, McAdams, D, McCarthy, C, Milch, H, Natale, S, Pappou, E, Paquette, I, Pulskamp, S, Rich, M, Savitt, L, Shafi, M, Steele, S, Stein, S, Tolbert, M, Varma, M, Vogler, S, Vuong, T, Wells, K, Wexner, S, Wo, J, Wright, J, Wunderlich, C, Campbell, K, Lim, M, Moug, S, Oliphant, R, Labaka-Aretaga, I, Ballester, C, Belen-Bueno, A, Vaquer-Casas, G, Jerez, J, Castillo, J, Paniagua-Cayetano, G, Codina-Cazador, A, Blanco-Colino, R, de la Portilla, F, Pascual-Damieta, M, Enriquez-Navascuez, JM, Martin-Fernández, M, Araujo-Ferreiro, M, Sanchez-García, C, Vico-García, E, Gallego-García, M, Jimenez, LM, Martinez-Sanchez, C, Carrillo-Moreno, J, Muñoz, A, Ramirez, L, Vigorita, V, Adams, R, Cornish, J, Davies, M, Evans, M, Torkington, J, and Turner, J

Published
2020
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27. Observations of phase changes in monoolein during high viscous injection

Author

Wells, DJ, Berntsen, P, Balaur, E, Kewish, CM, Adams, P, Aquila, A, Binns, J, Boutet, S, Broomhall, H, Caleman, C, Christofferson, A, Conn, CE, Dahlqvist, C, Flueckiger, L, Roque, FG, Greaves, TL, Hejazian, M, Hunter, M, Jazi, MH, Jonsson, HO, Pathirannahalage, SK, Kirian, RA, Kozlov, A, Kurta, RP, Marman, H, Mendez, D, Morgan, A, Nugent, K, Oberthuer, D, Quiney, H, Reinhardt, J, Saha, S, Sellberg, JA, Sierra, R, Wiedorn, M, Abbey, B, Martin, A, Darmanin, C, Wells, DJ, Berntsen, P, Balaur, E, Kewish, CM, Adams, P, Aquila, A, Binns, J, Boutet, S, Broomhall, H, Caleman, C, Christofferson, A, Conn, CE, Dahlqvist, C, Flueckiger, L, Roque, FG, Greaves, TL, Hejazian, M, Hunter, M, Jazi, MH, Jonsson, HO, Pathirannahalage, SK, Kirian, RA, Kozlov, A, Kurta, RP, Marman, H, Mendez, D, Morgan, A, Nugent, K, Oberthuer, D, Quiney, H, Reinhardt, J, Saha, S, Sellberg, JA, Sierra, R, Wiedorn, M, Abbey, B, Martin, A, and Darmanin, C

Abstract

Serial crystallography of membrane proteins often employs high-viscosity injectors (HVIs) to deliver micrometre-sized crystals to the X-ray beam. Typically, the carrier medium is a lipidic cubic phase (LCP) media, which can also be used to nucleate and grow the crystals. However, despite the fact that the LCP is widely used with HVIs, the potential impact of the injection process on the LCP structure has not been reported and hence is not yet well understood. The self-assembled structure of the LCP can be affected by pressure, dehydration and temperature changes, all of which occur during continuous flow injection. These changes to the LCP structure may in turn impact the results of X-ray diffraction measurements from membrane protein crystals. To investigate the influence of HVIs on the structure of the LCP we conducted a study of the phase changes in monoolein/water and monoolein/buffer mixtures during continuous flow injection, at both atmospheric pressure and under vacuum. The reservoir pressure in the HVI was tracked to determine if there is any correlation with the phase behaviour of the LCP. The results indicated that, even though the reservoir pressure underwent (at times) significant variation, this did not appear to correlate with observed phase changes in the sample stream or correspond to shifts in the LCP lattice parameter. During vacuum injection, there was a three-way coexistence of the gyroid cubic phase, diamond cubic phase and lamellar phase. During injection at atmospheric pressure, the coexistence of a cubic phase and lamellar phase in the monoolein/water mixtures was also observed. The degree to which the lamellar phase is formed was found to be strongly dependent on the co-flowing gas conditions used to stabilize the LCP stream. A combination of laboratory-based optical polarization microscopy and simulation studies was used to investigate these observations.

Published
2022

36. Chronic constipation in adults: Contemporary perspectives and clinical challenges. 1: Epidemiology, diagnosis, clinical associations, pathophysiology and investigation

Author

Scott, S M, Farmer, A D, Dinning, P G, Carrington, E V, Benninga, M A, Burgell, R E, Dimidi, E, Fikree, A, Ford, A C, Fox, M, Hoad, C L, Knowles, C H, Krogh, K, Nugent, K, Remes-Troche, J M, Whelan, K, and Corsetti, M

Subjects
chronic constipation, diagnosis, epidemiology, IBS-C, investigation, pathophysiology
Abstract

Chronic constipation is a prevalent disorder that affects patients’ quality of life and consumes resources in healthcare systems worldwide. In clinical practice, it is still considered a challenge as clinicians frequently are unsure as to which treatments to use and when. Over a decade ago, a Neurogastroenterology & Motility journal supplement devoted to the investigation and management of constipation was published (2009;21(Suppl.2)). This included seven articles, disseminating all themes covered during a preceding two-day meeting held in London, entitled ‘Current perspectives in chronic constipation: a scientific and clinical symposium’. In October 2018, the 3rd London Masterclass, entitled ‘Contemporary management of constipation’ was held, again over two days. All faculty members were invited to author two new review articles representing a collective synthesis of talks presented and discussions held during this meeting. PURPOSEThis article represents the first of these reviews, addressing epidemiology, diagnosis, clinical associations, pathophysiology and investigation. Clearly not all aspects of the condition can be covered in adequate detail; hence, there is a focus on particular ‘hot topics’ and themes that are of contemporary interest. The second review addresses management of chronic constipation, covering behavioural, conservative, medical and surgical therapies.

Published
2021

42. International consensus definition of low anterior resection syndrome

Author

Keane, C, Fearnhead, NS, Bordeianou, L, Christensen, P, Espin Basany, E, Laurberg, S, Mellgren, A, Messick, C, Orangio, GR, Verjee, A, Wing, K, Bissett, I, An, V, Bryant, A, Byrne, C, Chen, T, Clark, D, Croft, S, Dinning, P, Gladman, M, Heriot, A, Kariappa, S, Keck, J, Lubowski, D, Khera, A, Kirkwood, K, Petersen, D, Sloots, K, Totten, B, Weston, M, Andersen, P, Bachmann, C, Barht, H, Emmertsen, K, Faaborg, P, Gögenur, I, Ingerslev, P, Isaksen, D, Iversen, H, Iversen, L, Jacobsen, K, Jansen, T, Jocobsen, I, Juul, T, Kjær, D, Krogh, K, Majgaard, M, Mynster, A, Neuenschwander, A, Nielsen, C, Nielsen, M, Nielsen, R, Nielsen, T, Olsen, J, Poulsen, B, Rahr, H, Snedker, B, Sørensen, G, Stolzenburg, T, Vaabengaard, P, Acheson, A, Andreyev, J, Bach, S, Battersby, N, Bradbury, J, Brown, S, Cecil, T, Chapman, M, Chapman, S, Chave, H, Cook, T, Cuffy, L, Davies, J, Dawson, C, Dixon, J, Duff, S, Edwards, C, Geh, I, Hamilton, C, Hancock, L, Harji, D, Hill, J, Holtham, S, Jenkins, J, Johnston, R, Kapur, S, Maxwell‐Armstrong, C, McArthur, D, Moran, B, Norton, C, Nugent, K, Pateman, L, Perston, Y, Rockall, T, Sagar, P, Saunders, M, Sebag‐Montefiore, D, Senapati, A, Singh, B, Skaife, P, Smart, N, Sykes, H, Taylor, C, Thorpe, G, Tierney, G, Voyce, S, Walsh, C, Warren, O, Wheeler, J, Woodward, A, Winter, D, Abbott, S, Beban, V, Bennett, M, Chadwick, T, Collinson, R, Corbett, S, Dennett, E, Eglinton, T, Fraser, A, Glue, J, Hohaia, D, Menzi, E, O’Connor, M, Stevenson, D, Wells, C, Wolyncewicz, S, Woodfield, J, Bence, K, Boutros, M, Brueseke, M, DeKorte, J, Floruta, C, Francone, T, Frederick, F, Grasso, J, Gurland, B, Higgins, K, Hull, T, Keller, D, Laffan, A, Lovett, S, Marlatt, J, McAdams, D, McCarthy, C, Milch, H, Natale, S, Pappou, E, Paquette, I, Pulskamp, S, Rich, M, Savitt, L, Shafi, M, Steele, S, Stein, S, Tolbert, M, Varma, M, Vogler, S, Vuong, T, Wells, K, Wexner, S, Wo, J, Wright, J, Wunderlich, C, Campbell, K, Lim, M, Moug, S, Oliphant, R, Araujo‐Ferreiro, M, Ballester, C, Belen‐Bueno, A, Blanco‐Colino, R, Carrillo‐Moreno, J, Castillo, J, Codina‐Cazador, A, Enriquez‐Navascuez, JM, Gallego‐García, M, Jerez, J, Jimenez, LM, Labaka‐Aretaga, I, Martin‐Fernández, M, Martinez‐Sanchez, C, Muñoz, A, Paniagua‐Cayetano, G, Pascual‐Damieta, M, de la Portilla, F, Ramirez, L, Sanchez‐García, C, Vaquer‐Casas, G, Vico‐García, E, Vigorita, V, Adams, R, Cornish, J, Davies, M, Evans, M, Torkington, J, and Turner, J

Abstract

Aim: Low anterior resection syndrome (LARS) is pragmatically defined as disordered bowel function after rectal resection leading to a detriment in quality of life. This broad characterization does not allow for precise estimates of prevalence. The LARS score was designed as a simple tool for clinical evaluation of LARS. Although the LARS score has good clinical utility, it may not capture all important aspects that patients may experience. The aim of this collaboration was to develop an international consensus definition of LARS that encompasses all aspects of the condition and is informed by all stakeholders. Method: This international patient–provider initiative used an online Delphi survey, regional patient consultation meetings, and an international consensus meeting. Three expert groups participated: patients, surgeons and other health professionals from five regions (Australasia, Denmark, Spain, Great Britain and Ireland, and North America) and in three languages (English, Spanish, and Danish). The primary outcome measured was the priorities for the definition of LARS. Results: Three hundred twenty-five participants (156 patients) registered. The response rates for successive rounds of the Delphi survey were 86%, 96% and 99%. Eighteen priorities emerged from the Delphi survey. Patient consultation and consensus meetings refined these priorities to eight symptoms and eight consequences that capture essential aspects of the syndrome. Sampling bias may have been present, in particular, in the patient panel because social media was used extensively in recruitment. There was also dominance of the surgical panel at the final consensus meeting despite attempts to mitigate this. Conclusion: This is the first definition of LARS developed with direct input from a large international patient panel. The involvement of patients in all phases has ensured that the definition presented encompasses the vital aspects of the patient experience of LARS. The novel separation of symptoms and consequences may enable greater sensitivity to detect changes in LARS over time and with intervention.

Published
2020

43. Defining and expanding the phenotype of QARS-associated developmental epileptic encephalopathy

Author

Johannesen, Km, Mitter, D, Janowski, R, Roth, C, Toulouse, J, Poulat, Al, Ville, Dm, Chatron, N, Brilstra, E, Geleijns, K, Born, Ap, McLean, S, Nugent, K, Baynam, G, Poulton, C, Dreyer, L, Gration, D, Schulz, S, Dieckmann, A, Helbig, Kl, Merkenschlager, A, Jamra, R, Finck, A, Gardella, E, Hjalgrim, H, Mirzaa, G, Brancati, F, Bierhals, T, Denecke, J, Hempel, M, Lemke, Jr, Rubboli, G, Muschke, P, Guerrini, R, Vetro, A, Niessing, D, Lesca, G, and Møller, Rs

Subjects
TRANSFER-RNA-SYNTHETASE, ILAE COMMISSION, POSITION PAPER, MUTATIONS, CLASSIFICATION, DEFICIENCY, FEATURES
Published
2020

44. De Novo Variants in CNOT1, a Central Component of the CCR4-NOT Complex Involved in Gene Expression and RNA and Protein Stability, Cause Neurodevelopmental Delay

Author

Vissers, L.E.L.M., Kalvakuri, S., Boer, E. de, Geuer, S., Oud, M.M., Outersterp, I. van, Kwint, M.P., Witmond, M., Kersten, S., Polla, D.L., Weijers, D., Begtrup, A., McWalter, K., Ruiz, A., Gabau, E., Morton, J.E., Griffith, C., Weiss, K., Gamble, C., Bartley, J., Vernon, H.J., Brunet, K., Ruivenkamp, C., Kant, S.G., Kruszka, P., Larson, A., Afenjar, A., Billette de Villemeur, T., Nugent, K., Raymond, F.L., Venselaar, H., Demurger, F., Soler-Alfonso, C., Li, D., Bhoj, E., Hayes, I., Hamilton, N.P., Ahmad, A., Fisher, R., Born, M. van den, Willems, M., Sorlin, A., Delanne, J., Moutton, S., Christophe, P., Mau-Them, F.T., Vitobello, A., Goel, H., Massingham, L., Phornphutkul, C., Schwab, J., Keren, B., Charles, P., Vreeburg, M., Simone, L. De, Hoganson, G., Iascone, M., Milani, D., Evenepoel, L., Revencu, N., Ward, D.I., Burns, K., Krantz, I., Raible, S.E., Murrell, J.R., Wood, K., Cho, M.T., Bokhoven, H. van, Muenke, M., Kleefstra, T., Bodmer, R., Brouwer, A.P.M. de, Vissers, L.E.L.M., Kalvakuri, S., Boer, E. de, Geuer, S., Oud, M.M., Outersterp, I. van, Kwint, M.P., Witmond, M., Kersten, S., Polla, D.L., Weijers, D., Begtrup, A., McWalter, K., Ruiz, A., Gabau, E., Morton, J.E., Griffith, C., Weiss, K., Gamble, C., Bartley, J., Vernon, H.J., Brunet, K., Ruivenkamp, C., Kant, S.G., Kruszka, P., Larson, A., Afenjar, A., Billette de Villemeur, T., Nugent, K., Raymond, F.L., Venselaar, H., Demurger, F., Soler-Alfonso, C., Li, D., Bhoj, E., Hayes, I., Hamilton, N.P., Ahmad, A., Fisher, R., Born, M. van den, Willems, M., Sorlin, A., Delanne, J., Moutton, S., Christophe, P., Mau-Them, F.T., Vitobello, A., Goel, H., Massingham, L., Phornphutkul, C., Schwab, J., Keren, B., Charles, P., Vreeburg, M., Simone, L. De, Hoganson, G., Iascone, M., Milani, D., Evenepoel, L., Revencu, N., Ward, D.I., Burns, K., Krantz, I., Raible, S.E., Murrell, J.R., Wood, K., Cho, M.T., Bokhoven, H. van, Muenke, M., Kleefstra, T., Bodmer, R., and Brouwer, A.P.M. de

Abstract

Contains fulltext : 220423.pdf (Publisher’s version ) (Closed access), CNOT1 is a member of the CCR4-NOT complex, which is a master regulator, orchestrating gene expression, RNA deadenylation, and protein ubiquitination. We report on 39 individuals with heterozygous de novo CNOT1 variants, including missense, splice site, and nonsense variants, who present with a clinical spectrum of intellectual disability, motor delay, speech delay, seizures, hypotonia, and behavioral problems. To link CNOT1 dysfunction to the neurodevelopmental phenotype observed, we generated variant-specific Drosophila models, which showed learning and memory defects upon CNOT1 knockdown. Introduction of human wild-type CNOT1 was able to rescue this phenotype, whereas mutants could not or only partially, supporting our hypothesis that CNOT1 impairment results in neurodevelopmental delay. Furthermore, the genetic interaction with autism-spectrum genes, such as ASH1L, DYRK1A, MED13, and SHANK3, was impaired in our Drosophila models. Molecular characterization of CNOT1 variants revealed normal CNOT1 expression levels, with both mutant and wild-type alleles expressed at similar levels. Analysis of protein-protein interactions with other members indicated that the CCR4-NOT complex remained intact. An integrated omics approach of patient-derived genomics and transcriptomics data suggested only minimal effects on endonucleolytic nonsense-mediated mRNA decay components, suggesting that de novo CNOT1 variants are likely haploinsufficient hypomorph or neomorph, rather than dominant negative. In summary, we provide strong evidence that de novo CNOT1 variants cause neurodevelopmental delay with a wide range of additional co-morbidities. Whereas the underlying pathophysiological mechanism warrants further analysis, our data demonstrate an essential and central role of the CCR4-NOT complex in human brain development.

Published
2020

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