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2. Human-Induced Pluripotent Stem Cell (iPSC)-Derived GABAergic Neuron Differentiation in Bipolar Disorder.

Author

Schill, Daniel J., Attili, Durga, DeLong, Cynthia J., McInnis, Melvin G., Johnson, Craig N., Murphy, Geoffrey G., and O'Shea, K. Sue

Subjects
INDUCED pluripotent stem cells, GABAERGIC neurons, PLURIPOTENT stem cells, GABA, STEM cells, INTERNEURONS, CHLORIDE channels
Abstract

Bipolar disorder (BP) is a recurring psychiatric condition characterized by alternating episodes of low energy (depressions) followed by manias (high energy). Cortical network activity produced by GABAergic interneurons may be critical in maintaining the balance in excitatory/inhibitory activity in the brain during development. Initially, GABAergic signaling is excitatory; with maturation, these cells undergo a functional switch that converts GABAA channels from depolarizing (excitatory) to hyperpolarizing (inhibitory), which is controlled by the intracellular concentration of two chloride transporters. The earliest, NKCC1, promotes chloride entry into the cell and depolarization, while the second (KCC2) stimulates movement of chloride from the neuron, hyperpolarizing it. Perturbations in the timing or expression of NKCC1/KCC2 may affect essential morphogenetic events including cell proliferation, migration, synaptogenesis and plasticity, and thereby the structure and function of the cortex. We derived induced pluripotent stem cells (iPSC) from BP patients and undiagnosed control (C) individuals, then modified a differentiation protocol to form GABAergic interneurons, harvesting cells at sequential stages of differentiation. qRT-PCR and RNA sequencing indicated that after six weeks of differentiation, controls transiently expressed high levels of NKCC1. Using multi-electrode array (MEA) analysis, we observed that BP neurons exhibit increased firing, network bursting and decreased synchrony compared to C. Understanding GABA signaling in differentiation may identify novel approaches and new targets for treatment of neuropsychiatric disorders such as BP. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Cohort Profile Update: The Heinz C. Prechter Longitudinal Study of Bipolar Disorder

Author

Yocum, Anastasia K, primary, Anderau, Steve, additional, Bertram, Holli, additional, Burgess, Helen J, additional, Cochran, Amy L, additional, Deldin, Patricia J, additional, Evans, Simon J, additional, Han, Peisong, additional, Jenkins, Paul M, additional, Kaur, Ravleen, additional, Langenecker, Scott A, additional, Marshall, David F, additional, Mower Provost, Emily, additional, Sue O’Shea, K, additional, Ryan, Kelly A, additional, Sperry, Sarah H, additional, Smith, Shawna N, additional, Tso, Ivy F, additional, Versha, Kritika M, additional, Wright, Brittany M, additional, Zöllner, Sebastian, additional, and McInnis, Melvin G, additional

Published
2023
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12. Chlorhexidine versus povidone–iodine skin antisepsis before upper limb surgery (CIPHUR) : an international multicentre prospective cohort study

Author

Wade, Ryckie G., Bourke, Gráinne, Wormald, Justin C. R., Totty, Joshua Philip, Stanley, Guy Henry Morton, Lewandowski, Andrew, Rakhra, Sandeep Singh, Gardiner, Matthew D., Bindra, R., Sher, M., Thomas, M., Morgan, S. D. J., Hwang, B., Santucci, W., Tran, P., Kopp, L., Kunc, V., Hamdi, A., Grieve, P. P., Mukhaizeem, S. A., Blake, K., Cuggy, C., Dolan, R., Downes, E., Geary, E., Ghadge, A., Gorman, P., Jonson, M., Jumper, N., Kelly, S., Leddy, L., McMahon, M. E., McNamee, C., Miller, P., Murphy, B., O'Halloran, L., O’Shea, K., Skeens, J., Staunton, S., Timon, F., Woods, J., Cortinovis, U., Sala, L., Zingarello, V., Jusoh, M. H., Sadagatullah, A. N., Georgieva, G., Pejkova, S., Nikolovska, B., Srbov, B., Hamid, H. K. S., Mustafa, M., Abdelrahman, M., Amin, S. M. M., Bhatti, D., Rahman, K. M. A., Jumabhoy, I., Kiely, J., Kieran, I., Lo, A. C. Q., Wong, K Y., Allan, A. Y., Armes, H., Horwitz, M. D., Ioannidi, L., Masterton, G., Chu, H., Talawadekar, G. D., Tong, K. S., Chan, M., Tredgett, M., Hardie, C., Powell-Smith, E., Gilham, N., Prokopenko, M., Ahmad, R., Davies, J., Zhen, S., Dargan, D., Pinder, R. M., Koziara, M., Martin, R., Reay, E., Cochrane, E., Elbatawy, A., Green, F., Griffiths, T., Higginbotham, G., Louette, S., McCauley, G., Natalwala, I., Salt, E., Ahmed, R., Goon, P., Manton, R., Segaren, N., Cheung, G., Mahoney, R., Sen, S., Clarkson, D., Collins, M., Bolt, A., Lokanathan, P., Ng, A., Jones, G., Jones, J. W. M., Kabariti, R., Rhee, S. J., Herron, J., Kay, A., Cheung, L. K., Thomson, D., Jugdey, R. S., Yoon, H., L, Z., Southgate, J., Brennan, C., Kiani, S., Zabaglo, M., Haider, Z. A., Poulter, R., Sheik-Ali, A., Watts, A., Jemec, B., Redgrave, N., Dupley, L., Greenhalgh, M., Vella, J., Harris, H., Robinson, A. V., Dupre, S., Teelucksingh, S., Gargan, A., Hettiaratchy, S., Jain, A., Kwasnicki, R., Lee, A., Thakkar, M., Berwick, D., Ismail, N., Mahdi, M., Rodrigues, Jeremy, Liew, C., Saadya, A., Clarkson, M., Brady, C., Harrison, R., Rayner, A., Nolan, G., Phillips, B., Madhusudan, N., and HASH(0x5651c97f7e70)

Subjects
Adult, AcademicSubjects/MED00910, Chlorhexidine, Bjs/2, Antisepsis, General Medicine, Upper Extremity, Preoperative Care, Humans, Original Article, Prospective Studies, AcademicSubjects/MED00010, Child, Povidone-Iodine, RA, RD
Abstract

Introduction Surgical site infection (SSI) is the most common and costly complication of surgery. International guidelines recommend topical alcoholic chlorhexidine (CHX) before surgery. However, upper limb surgeons continue to use other antiseptics, citing a lack of applicable evidence, and concerns related to open wounds and tourniquets. This study aimed to evaluate the safety and effectiveness of different topical antiseptics before upper limb surgery. Methods This international multicentre prospective cohort study recruited consecutive adults and children who underwent surgery distal to the shoulder joint. The intervention was use of CHX or povidone–iodine (PVI) antiseptics in either aqueous or alcoholic form. The primary outcome was SSI within 90 days. Mixed-effects time-to-event models were used to estimate the risk (hazard ratio (HR)) of SSI for patients undergoing elective and emergency upper limb surgery. Results A total of 2454 patients were included. The overall risk of SSI was 3.5 per cent. For elective upper limb surgery (1018 patients), alcoholic CHX appeared to be the most effective antiseptic, reducing the risk of SSI by 70 per cent (adjusted HR 0.30, 95 per cent c.i. 0.11 to 0.84), when compared with aqueous PVI. Concerning emergency upper limb surgery (1436 patients), aqueous PVI appeared to be the least effective antiseptic for preventing SSI; however, there was uncertainty in the estimates. No adverse events were reported. Conclusion The findings align with the global evidence base and international guidance, suggesting that alcoholic CHX should be used for skin antisepsis before clean (elective upper limb) surgery. For emergency (contaminated or dirty) upper limb surgery, the findings of this study were unclear and contradict the available evidence, concluding that further research is necessary., This international study recruited 2454 children and adults undergoing surgery on their upper limb (arm or hand), from 42 hospitals worldwide. The overall risk of infection after surgery was 3.5 per cent. Before planned (elective) surgery, if surgeons cleaned the skin with alcoholic chlorhexidine, then the risk of infection was reduced by 70 per cent.

Published
2021

19. Epigenetic silencing of engineered L1 retrotransposition events in human embryonic carcinoma cells

Author

Garcia-Perez, Jose L., Morell, Maria, Scheys, Joshua O., Kulpa, Deanna A., Morell, Santiago, Carter, Christoph C., Hammer, Gary D., Collins, Kathleen L., O'Shea, K. Sue, Menendez, Pablo, and Moran, John V.

Subjects
Genetic aspects, Research, Health aspects, Retrotransposons -- Health aspects -- Genetic aspects -- Research, Genetic engineering -- Research -- Health aspects -- Genetic aspects, Cancer genetics -- Research -- Genetic aspects, Gene silencing -- Research -- Health aspects -- Genetic aspects, Cancer cells -- Genetic aspects -- Health aspects -- Research, Cancer -- Genetic aspects
Abstract

Human ECs have a transcription profile similar to human embryonic stem cells, and have been used as a model of early human development (9). Previous studies demonstrated that human L1s [...], Long interspersed element-1 (LINE-1 or L1) retrotransposition continues to affect human genome evolution (1,2). Lis can retrotranspose in the germline, during early development and in select somatic cells (3-8); however, the host response to L1 retrotransposition remains largely unexplored. Here we show that reporter genes introduced into the genome of various human embryonic carcinoma-derived cell lines (ECs) by L1 retrotransposition are rapidly and efficiently silenced either during or immediately after their integration. Treating ECs with histone deacetylase inhibitors rapidly reverses this silencing, and chromatin immunoprecipitation experiments revealed that reactivation of the reporter gene was correlated with changes in chromatin status at the L1 integration site. Under our assay conditions, rapid silencing was also observed when reporter genes were delivered into ECs by mouse L1s and a zebrafish LINE-2 element, but not when similar reporter genes were delivered into ECs by Moloney murine leukaemia virus or human immunodeficiency virus, suggesting that these integration events are silenced by distinct mechanisms. Finally, we demonstrate that subjecting ECs to culture conditions that promote differentiation attenuates the silencing of reporter genes delivered by L1 retrotransposition, but that differentiation, in itself, is not sufficient to reactivate previously silenced reporter genes. Thus, our data indicate that ECs differ from many differentiated cells in their ability to silence reporter genes delivered by L1 retrotransposition.

Published
2010
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20. L1 retrotransposition in human neural progenitor cells

Author

Coufal, Nicole G., Garcia-Perez, Jose L., Peng, Grace E., Yeo, Gene W., Mu, Yangling, Lovci, Michael T., Morell, Maria, O'Shea, K. Sue, Moran, John V., and Gage, Fred H.

Subjects
Physiological aspects, Research, Nervous system -- Research -- Physiological aspects, Cell culture -- Research -- Physiological aspects, DNA -- Research -- Physiological aspects
Abstract

The human nervous system is complex, containing approximately [10.sup.5] synapses with a vast diversity of neuronal cell types and connections that are influenced by complex and incompletely understood environmental and [...], Long interspersed element 1 (LINE-1 or L1) retrotransposons have markedly affected the human genome. L1s must retrotranspose in the germ line or during early development to ensure their evolutionary success, yet the extent to which this process affects somatic cells is poorly understood. We previously demonstrated that engineered human L1s can retrotranspose in adult rat hippocampus progenitor cells in vitro and in the mouse brain in vivo (1). Here we demonstrate that neural progenitor cells isolated from human fetal brain and derived from human embryonic stem cells support the retrotransposition of engineered human L1s in vitro. Furthermore, we developed a quantitative multiplex polymerase chain reaction that detected an increase in the copy number of endogenous L1s in the hippocampus, and in several regions of adult human brains, when compared to the copy number of endogenous L1s in heart or liver genomic DNAs from the same donor. These data suggest that de novo L1 retrotransposition events may occur in the human brain and, in principle, have the potential to contribute to individual somatic mosaicism.

Published
2009

21. Same data, different conclusions: Radical dispersion in empirical results when independent analysts operationalize and test the same hypothesis

Author

Schweinsberg, M., Feldman, M., Staub, N., van den Akker, O.R., van Aert, R.C.M., van Assen, M.A.L.M., Liu, Y., Althoff, T., Heer, J., Kale, A., Mohamed, Z., Amireh, H., Venkatesh Prasad, V., Bernstein, A., Robinson, E., Snellman, K., Sommer, S.A., Otner, S.M.G., Robinson, D.A., Madan, N., Silberzahn, R., Goldstein, P., Tierney, W., Murase, T., Mandl, B., Viganola, D., Strobl, C., Schaumans, C.B.C., Kelchtermans, S., Naseeb, C., Mason Garrison, S., Yarkoni, T., Richard Chan, C. S., Adie, P., Alaburda, P., Albers, C., Alspaugh, S., Alstott, J., Nelson, A.A., Ariño de la Rubia, E., Arzi, A., Bahník, Š., Baik, J., Winther Balling, L., Banker, S., Baranger, D.A.A., Barr, D.J., Barros-Rivera, B., Bauer, M., Blaise, E., Boelen, L., Bohle Carbonell, K., Briers, R.A., Burkhard, O., Canela, M.A., Castrillo, L., Catlett, T., Chen, O., Clark, M., Cohn, B., Coppock, A., Cugueró-Escofet, N., Curran, P.G., Cyrus-Lai, W., Dai, D., Valentino Dalla Riva, G., Danielsson, H., Russo, R.d.F.S.M., de Silva, N., Derungs, C., Dondelinger, F., Duarte de Souza, C., Tyson Dube, B., Dubova, M., Dunn, B.M., Edelsbrunner, P.A., Finley, S., Fox, N., Gnambs, T., Gong, Y., Grand, E., Greenawalt, B., Han, D., Hanel, P.H.P., Hong, A.B., Hood, D., Hsueh, J., Huang, L., Hui, K.N., Hultman, K.A., Javaid, A., Ji Jiang, L., Jong, J., Kamdar, J., Kane, D., Kappler, G., Kaszubowski, E., Kavanagh, C.M., Khabsa, M., Kleinberg, B., Kouros, J., Krause, H., Krypotos, A.M., Lavbič, D., Ling Lee, R., Leffel, T., Yang Lim, W., Liverani, S., Loh, B., Lønsmann, D., Wei Low, J., Lu, A., MacDonald, K., Madan, C.R., Hjorth Madsen, L., Maimone, C., Mangold, A., Marshall, A., Matskewich, H.E., Mavon, K., McLain, K.L., McNamara, A.A., McNeill, M., Mertens, U., Miller, D., Moore, B., Moore, A., Nantz, E., Nasrullah, Z., Nejkovic, V., Nell, C.S., Nilsonne, G., Nolan, R., O'Brien, C.E., O'Neill, P., O'Shea, K., Olita, T., Otterbacher, J., Palsetia, D., Pereira, B., Pozdniakov, I., Protzko, J., Reyt, J.N., Riddle, T., (Akmal) Ridhwan Omar Ali, A., Ropovik, I., Rosenberg, J.M., Rothen, S., Schulte-Mecklenbeck, M., Sharma, N., Shotwell, G., Skarzynski, M., Stedden, W., Stodden, V., Stoffel, M.A., Stoltzman, S., Subbaiah, S., Tatman, R., Thibodeau, P.H., Tomkins, S., Valdivia, A., Druijff-van de Woestijne, G.B., Viana, L., Villesèche, F., Wadsworth, W.D., Wanders, F., Watts, K., Wells, J.D., Whelpley, C.E., Won, A., Wu, L., Yip, A., Youngflesh, C., Yu, J.C., Zandian, A., Zhang, L., Zibman, C., Uhlmann, E.L., Social Networks, Solidarity and Inequality, Leerstoel Buskens, Structural geology and EM, Experimental psychopathology, Leerstoel Engelhard, Department of Methodology and Statistics, Tilburg Experience Sampling Center (TESC), University of Zurich, Schweinsberg, Martin, Psychometrics and Statistics, Social Networks, Solidarity and Inequality, Leerstoel Buskens, Structural geology and EM, Experimental psychopathology, and Leerstoel Engelhard

Subjects
Organizational Behavior and Human Resource Management, TRANSPARENCY, 10009 Department of Informatics, Sample (statistics), 000 Computer science, knowledge & systems, 1407 Organizational Behavior and Human Resource Management, Scientific robustness, 3202 Applied Psychology, Scientific transparency, REPRODUCIBILITY, 650 Management & public relations, medicine, Econometrics, MANAGEMENT, QUALITY, business, Robustness (economics), Research question, Verbosity, CRISIS, Applied Psychology, Analysis-contingent results, Operationalization, Psykologi (exklusive tillämpad psykologi), 11476 Digital Society Initiative, AVAILABILITY, Researcher degrees of freedom, SCIENCE, cs_r, SOCIAL-PSYCHOLOGY, Crowdsourcing data analysis, Research reliability, Psychology (excluding Applied Psychology), Open data, Ranking, Transparency (graphic), REPLICABILITY, REPLICATION, medicine.symptom, Psychology
Abstract

The project was funded by a research grant from INSEAD and was also supported by the Swiss National Science Foundation under grant number 143411., In this crowdsourced initiative, independent analysts used the same dataset to test two hypotheses regarding the effects of scientists’ gender and professional status on verbosity during group meetings. Not only the analytic approach but also the operationalizations of key variables were left unconstrained and up to individual analysts. For instance, analysts could choose to operationalize status as job title, institutional ranking, citation counts, or some combination. To maximize transparency regarding the process by which analytic choices are made, the analysts used a platform we developed called DataExplained to justify both preferred and rejected analytic paths in real time. Analyses lacking sufficient detail, reproducible code, or with statistical errors were excluded, resulting in 29 analyses in the final sample. Researchers reported radically different analyses and dispersed empirical outcomes, in a number of cases obtaining significant effects in opposite directions for the same research question. A Boba multiverse analysis demonstrates that decisions about how to operationalize variables explain variability in outcomes above and beyond statistical choices (e.g., covariates). Subjective researcher decisions play a critical role in driving the reported empirical results, underscoring the need for open data, systematic robustness checks, and transparency regarding both analytic paths taken and not taken. Implications for organizations and leaders, whose decision making relies in part on scientific findings, consulting reports, and internal analyses by data scientists, are discussed., INSEAD, Swiss National Science Foundation (SNSF) European Commission 143411

Published
2021
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22. Same data, different conclusions: Radical dispersion in empirical results when independent analysts operationalize and test the same hypothesis

Author

Social Networks, Solidarity and Inequality, Leerstoel Buskens, Structural geology and EM, Experimental psychopathology, Leerstoel Engelhard, Schweinsberg, M., Feldman, M., Staub, N., van den Akker, O.R., van Aert, R.C.M., van Assen, M.A.L.M., Liu, Y., Althoff, T., Heer, J., Kale, A., Mohamed, Z., Amireh, H., Venkatesh Prasad, V., Bernstein, A., Robinson, E., Snellman, K., Sommer, S.A., Otner, S.M.G., Robinson, D.A., Madan, N., Silberzahn, R., Goldstein, P., Tierney, W., Murase, T., Mandl, B., Viganola, D., Strobl, C., Schaumans, C.B.C., Kelchtermans, S., Naseeb, C., Mason Garrison, S., Yarkoni, T., Richard Chan, C. S., Adie, P., Alaburda, P., Albers, C., Alspaugh, S., Alstott, J., Nelson, A.A., Ariño de la Rubia, E., Arzi, A., Bahník, Š., Baik, J., Winther Balling, L., Banker, S., Baranger, D.A.A., Barr, D.J., Barros-Rivera, B., Bauer, M., Blaise, E., Boelen, L., Bohle Carbonell, K., Briers, R.A., Burkhard, O., Canela, M.A., Castrillo, L., Catlett, T., Chen, O., Clark, M., Cohn, B., Coppock, A., Cugueró-Escofet, N., Curran, P.G., Cyrus-Lai, W., Dai, D., Valentino Dalla Riva, G., Danielsson, H., Russo, R.d.F.S.M., de Silva, N., Derungs, C., Dondelinger, F., Duarte de Souza, C., Tyson Dube, B., Dubova, M., Dunn, B.M., Edelsbrunner, P.A., Finley, S., Fox, N., Gnambs, T., Gong, Y., Grand, E., Greenawalt, B., Han, D., Hanel, P.H.P., Hong, A.B., Hood, D., Hsueh, J., Huang, L., Hui, K.N., Hultman, K.A., Javaid, A., Ji Jiang, L., Jong, J., Kamdar, J., Kane, D., Kappler, G., Kaszubowski, E., Kavanagh, C.M., Khabsa, M., Kleinberg, B., Kouros, J., Krause, H., Krypotos, A.M., Lavbič, D., Ling Lee, R., Leffel, T., Yang Lim, W., Liverani, S., Loh, B., Lønsmann, D., Wei Low, J., Lu, A., MacDonald, K., Madan, C.R., Hjorth Madsen, L., Maimone, C., Mangold, A., Marshall, A., Matskewich, H.E., Mavon, K., McLain, K.L., McNamara, A.A., McNeill, M., Mertens, U., Miller, D., Moore, B., Moore, A., Nantz, E., Nasrullah, Z., Nejkovic, V., Nell, C.S., Nilsonne, G., Nolan, R., O'Brien, C.E., O'Neill, P., O'Shea, K., Olita, T., Otterbacher, J., Palsetia, D., Pereira, B., Pozdniakov, I., Protzko, J., Reyt, J.N., Riddle, T., (Akmal) Ridhwan Omar Ali, A., Ropovik, I., Rosenberg, J.M., Rothen, S., Schulte-Mecklenbeck, M., Sharma, N., Shotwell, G., Skarzynski, M., Stedden, W., Stodden, V., Stoffel, M.A., Stoltzman, S., Subbaiah, S., Tatman, R., Thibodeau, P.H., Tomkins, S., Valdivia, A., Druijff-van de Woestijne, G.B., Viana, L., Villesèche, F., Wadsworth, W.D., Wanders, F., Watts, K., Wells, J.D., Whelpley, C.E., Won, A., Wu, L., Yip, A., Youngflesh, C., Yu, J.C., Zandian, A., Zhang, L., Zibman, C., Uhlmann, E.L., Social Networks, Solidarity and Inequality, Leerstoel Buskens, Structural geology and EM, Experimental psychopathology, Leerstoel Engelhard, Schweinsberg, M., Feldman, M., Staub, N., van den Akker, O.R., van Aert, R.C.M., van Assen, M.A.L.M., Liu, Y., Althoff, T., Heer, J., Kale, A., Mohamed, Z., Amireh, H., Venkatesh Prasad, V., Bernstein, A., Robinson, E., Snellman, K., Sommer, S.A., Otner, S.M.G., Robinson, D.A., Madan, N., Silberzahn, R., Goldstein, P., Tierney, W., Murase, T., Mandl, B., Viganola, D., Strobl, C., Schaumans, C.B.C., Kelchtermans, S., Naseeb, C., Mason Garrison, S., Yarkoni, T., Richard Chan, C. S., Adie, P., Alaburda, P., Albers, C., Alspaugh, S., Alstott, J., Nelson, A.A., Ariño de la Rubia, E., Arzi, A., Bahník, Š., Baik, J., Winther Balling, L., Banker, S., Baranger, D.A.A., Barr, D.J., Barros-Rivera, B., Bauer, M., Blaise, E., Boelen, L., Bohle Carbonell, K., Briers, R.A., Burkhard, O., Canela, M.A., Castrillo, L., Catlett, T., Chen, O., Clark, M., Cohn, B., Coppock, A., Cugueró-Escofet, N., Curran, P.G., Cyrus-Lai, W., Dai, D., Valentino Dalla Riva, G., Danielsson, H., Russo, R.d.F.S.M., de Silva, N., Derungs, C., Dondelinger, F., Duarte de Souza, C., Tyson Dube, B., Dubova, M., Dunn, B.M., Edelsbrunner, P.A., Finley, S., Fox, N., Gnambs, T., Gong, Y., Grand, E., Greenawalt, B., Han, D., Hanel, P.H.P., Hong, A.B., Hood, D., Hsueh, J., Huang, L., Hui, K.N., Hultman, K.A., Javaid, A., Ji Jiang, L., Jong, J., Kamdar, J., Kane, D., Kappler, G., Kaszubowski, E., Kavanagh, C.M., Khabsa, M., Kleinberg, B., Kouros, J., Krause, H., Krypotos, A.M., Lavbič, D., Ling Lee, R., Leffel, T., Yang Lim, W., Liverani, S., Loh, B., Lønsmann, D., Wei Low, J., Lu, A., MacDonald, K., Madan, C.R., Hjorth Madsen, L., Maimone, C., Mangold, A., Marshall, A., Matskewich, H.E., Mavon, K., McLain, K.L., McNamara, A.A., McNeill, M., Mertens, U., Miller, D., Moore, B., Moore, A., Nantz, E., Nasrullah, Z., Nejkovic, V., Nell, C.S., Nilsonne, G., Nolan, R., O'Brien, C.E., O'Neill, P., O'Shea, K., Olita, T., Otterbacher, J., Palsetia, D., Pereira, B., Pozdniakov, I., Protzko, J., Reyt, J.N., Riddle, T., (Akmal) Ridhwan Omar Ali, A., Ropovik, I., Rosenberg, J.M., Rothen, S., Schulte-Mecklenbeck, M., Sharma, N., Shotwell, G., Skarzynski, M., Stedden, W., Stodden, V., Stoffel, M.A., Stoltzman, S., Subbaiah, S., Tatman, R., Thibodeau, P.H., Tomkins, S., Valdivia, A., Druijff-van de Woestijne, G.B., Viana, L., Villesèche, F., Wadsworth, W.D., Wanders, F., Watts, K., Wells, J.D., Whelpley, C.E., Won, A., Wu, L., Yip, A., Youngflesh, C., Yu, J.C., Zandian, A., Zhang, L., Zibman, C., and Uhlmann, E.L.

Published
2021

23. Noggin and chordin have distinct activities in promoting lineage commitment of mouse embryonic stem (ES) Cells

Author

Gratsch, Theresa E. and O'Shea, K. Sue

Subjects
Embryology -- Research, Stem cells -- Research, Cell differentiation -- Physiological aspects, Neurons -- Physiological aspects, Biological sciences
Abstract

To examine the role of secreted signaling molecules and neurogenic genes in early development, we have developed a culture system for the controlled differentiation of mouse embryonic stem (ES) cells. In the current investigation, two of the earliest identified BMP antagonists/neural-inducing factors, noggin and chordin, were expressed in pluripotent mouse ES cells. Neurons were present as early as 24 h following transfection of ES cells with a pCS2/noggin expression plasmid, with differentiation peaking at 72 h. With neuronal differentiation, stem cell marker genes were down-regulated and neural determination genes expressed. Coculture experiments and exposure to noggin-conditioned medium produced similar neuronal differentiation of control ES cells, while addition of BMP-4 to noggin expressants strikingly inhibited neuronal differentiation. Transfection of ES cells with a pCS2/chordin expression vector or exposure to chordin-conditioned medium produced a more complex pattern of differentiation; ES cells formed neurons, mesenchymal cells as well as N-CAM-positive, nestin-positive neuroepithelial progenitors. These data suggest that, consistent with their different expression fields, noggin and chordin may play distinct roles in patterning the early mouse embryo. Key Words: BMP; differentiation; induction; neuron; nervous system; node; transfection.

Published
2002

27. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene

Author

Ferrara, Napoleone, Carver-Moore, Karen, Chen, Helen, Dowd, Mary, Lu, Lucy, O'Shea, K. Sue, Powell-Braxton, Lyn, Hillan, Kenneth J., and Moore, Mark W.

Subjects
Embryology -- Research, Growth factors -- Physiological aspects, Neovascularization -- Observations, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The disruption of a single vascular endothelial growth factor (VEGF) gene in the embryonic stem (ES) cells causes lethality within 11-12 days in a nude mouse model. Defective angiogenesis and blood-island development produces several physiological and pathological abnormalities. This confirms the importance of VEGF in pathological angiogenesis. The ES cells lacking VEGF allele are inactive in tumorigenesis.

Published
1996

29. Correction to: Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Author

Griffiths, E. A., Hodson, J., Vohra, R. S., Marriott, P., Katbeh, T., Zino, S., Nassar, A. H. M., Kirkham, A. J., Pasquali, S., Johnstone, M., Spreadborough, P., Alderson, D., Fenwick, S., Elmasry, M., Nunes, Q. M., Kennedy, D., Khan, R. B., Khan, M. A. S., Magee, C. J., Jones, S. M., Mason, D., Parappally, C. P., Mathur, P., Saunders, M., Jamel, S., Haque, S. U., Zafar, S., Shiwani, M. H., Samuel, N., Dar, F., Jackson, A., Lovett, B., Dindyal, S., Winter, H., Fletcher, T., Rahman, S., Wheatley, K., Nieto, T., Ayaani, S., Youssef, H., Nijjar, R. S., Watkin, H., Naumann, D., Emesih, S., Sarmah, P. B., Lee, K., Joji, N., Lambert, J., Heath, J., Teasdale, R. L., Weerasinghe, C., Needham, P. J., Welbourn, H., Forster, L., Finch, D., Blazeby, J. M., Robb, W., Mcnair, A. G. K., Hrycaiczuk, A., Charalabopoulos, A., Kadirkamanathan, S., Tang, C. -B., Jayanthi, N. V. G., Noor, N., Dobbins, B., Cockbain, A. J., Nilsen-Nunn, A., de Siqueira, J., Pellen, M., Cowley, J. B., W. -M., Ho, Miu, V., White, T. J., Hodgkins, K. A., Kinghorn, A., Tutton, M. G., Al-Abed, Y. A., Menzies, D., Ahmad, A., Reed, J., Khan, S., Monk, D., Vitone, L. J., Murtaza, G., Joel, A., Brennan, S., Shier, D., Zhang, C., Yoganathan, T., Robinson, S. J., Mccallum, I. J. D., Jones, M. J., Elsayed, M., Tuck, L., Wayman, J., Carney, K., Aroori, S., Hosie, K. B., Kimble, A., Bunting, D. M., Fawole, A. S., Basheer, M., Dave, R. V., Sarveswaran, J., Jones, E., Kendal, C., Tilston, M. P., Gough, M., Wallace, T., Singh, S., Mockford, J. D. K. A., Issa, E., Shah, N., Chauhan, N., Wilson, T. R., Forouzanfar, A., Wild, J. R. L., Nofal, E., Bunnell, C., Madbak, K., Rao, S. T. V., Devoto, L., Siddiqi, N., Khawaja, Z., Hewes, J. C., Gould, L., Chambers, A., Rodriguez, D. U., Sen, G., Robinson, S., Bartlett, F., Rae, D. M., Stevenson, T. E. J., Sarvananthan, K., Dwerryhouse, S. J., Higgs, S. M., Old, O. J., Hardy, T. J., Hornby, R. S. S. T., Keogh, K., Frank, L., Al-Akash, M., Upchurch, E. A., Frame, R. J., Hughes, M., Jelley, C., Weaver, S., Roy, S., Sillo, T. O., Galanopoulos, G., Cuming, T., Cunha, P., Tayeh, S., Kaptanis, S., Heshaishi, M., Eisawi, A., Abayomi, M., Ngu, W. S., Fleming, K., Bajwa, D. S., Chitre, V., Aryal, K., Ferris, P., Silva, M., Mohamed, S. L. S., Khawaja, A., Hussain, A., Ghazanfar, M. A., Bellini, M. I., Ebdewi, H., Elshaer, M., Gravante, G., Drake, B., Ogedegbe, A., Mukherjee, D., Arhi, C., Iqbal, L. G. N., Watson, N. F., Aggarwal, S. K., Orchard, P., Villatoro, E., Willson, P. D., Mok, K. W. J., Woodman, T., Deguara, J., Garcea, G., Babu, B. I., Dennison, A. R., Malde, D., Lloyd, D., Satheesan, S., Al-Taan, O., Boddy, A., Slavin, J. P., Jones, R. P., Ballance, L., Gerakopoulos, S., Jambulingam, P., Mansour, S., Sakai, N., Acharya, V., Sadat, M. M., Karim, L., Larkin, D., Amin, K., Khan, A., Law, J., Jamdar, S., Smith, S. R., Sampat, K., O'Shea, K. M., Manu, M., Asprou, F. M., Malik, N. S., Chang, J., Lewis, M., Roberts, G. P., Karavadra, B., Photi, E., Hewes, J., Rodriguez, D., O'Reilly, D. A., Rate, A. J., Sekhar, H., Henderson, L. T., Starmer, B. Z., Coe, P. O., Tolofari, S., Barrie, J., Bashir, G., Sloane, J., Madanipour, S., Halkias, C., Trevatt, A. E. J., Borowski, D. W., Hornsby, J., Courtney, M. J., Virupaksha, S., Seymour, K., Hawkins, H., Bawa, S., Gallagher, P. V., Reid, A., Wood, P., Finch, J. G., Guy Finch, J., Parmar, J., Stirland, E., Gardner-Thorpe, J., Al-Muhktar, A., Peterson, M., Majeed, A., Bajwa, F. M., Martin, J., Choy, A., Tsang, A., Pore, N., Andrew, D. R., Al-Khyatt, W., Bhandari, C. T. S., Subramanium, D., Toh, S. K. C., Carter, N. C., Tate, S., Pearce, B., Wainwright, D., Mercer, S. J., Knight, B., Vijay, V., Alagaratnam, S., Sinha, S., El-Hasani, S. S., Hussain, A. A., Bhattacharya, V., Kansal, N., Fasih, T., Jackson, C., Siddiqui, M. N., Chishti, I. A., Fordham, I. J., Siddiqui, Z., Bausbacher, H., Geogloma, I., Gurung, K., Tsavellas, G., Basynat, P., Shrestha, A. K., Basu, S., Harilingam, A. C. M., Rabie, M., Akhtar, M., Kumar, P., Jafferbhoy, S. F., Hussain, N., Raza, S., Haque, M., Alam, I., Aseem, R., Patel, S., Asad, M., Booth, M. I., Ball, W. R., Wood, C. P. J., Pinho-Gomes, A. C., Kausar, A., Obeidallah, M. R., Varghase, J., Lodhia, J., Bradley, D., Rengifo, C., Lindsay, D., Gopalswamy, S., Finlay, I., Wardle, S., Bullen, N., Iftikhar, S. Y., Awan, A., Ahmed, J., Leeder, P., Fusai, G., Bond-Smith, G., Psica, A., Puri, Y., Hou, D., Noble, F., Szentpali, K., Broadhurst, J., Date, R., Hossack, M. R., Goh, Y. L., Turner, P., Shetty, V., Riera, M., Macano, C. A. W., Sukha, A., Preston, S. R., Hoban, J. R., Puntis, D. J., Williams, S. V., Krysztopik, R., Kynaston, J., Batt, J., Doe, M., Goscimski, A., Jones, G. H., Hall, C., Carty, N., Panteleimonitis, S., Gunasekera, R. T., Sheel, A. R. G., Lennon, H., Hindley, C., Reddy, M., Kenny, R., Elkheir, N., Mcglone, E. R., Rajaganeshan, R., Hancorn, K., Hargreaves, A., Prasad, R., Longbotham, D. A., Vijayanand, D., Wijetunga, I., Ziprin, P., Nicolay, C. R., Yeldham, G., Read, E., Gossage, J. A., Rolph, R. C., Ebied, H., Phull, M., Khan, M. A., Popplewell, M., Kyriakidis, D., Henley, N., Packer, J. R., Derbyshire, L., Porter, J., Appleton, S., Farouk, M., Basra, M., Jennings, N. A., Ali, S., Kanakala, V., Ali, H., Lane, R., Dickson-Lowe, R., Zarsadias, P., Mirza, D., Puig, S., Amari, K. A., Vijayan, D., Sutcliffe, R., Marudanayagam, R., Hamady, Z., Prasad, A. R., Patel, A., Durkin, D., Kaur, P., Bowen, L., Byrne, J. P., Pearson, K. L., Delisle, T. G., Davies, J., Tomlinson, M. A., Johnpulle, M. A., Slawinski, C., Macdonald, A., Nicholson, J., Newton, K., Mbuvi, J., Farooq, A., Mothe, B. S., Zafrani, Z., Brett, D., Francombe, J., Barnes, J., Cheung, M., Al-Bahrani, A. Z., Preziosi, G., Urbonas, T., Alberts, J., Mallik, M., Patel, K., Segaran, A., Doulias, T., Sufi, P. A., Yao, C., Pollock, S., Manzelli, A., Wajed, S., Kourkulos, M., Pezzuto, R., Wadley, M., Hamilton, E., Jaunoo, S., Padwick, R., Sayegh, M., Newton, R. C., Hebbar, M., Farag, S. F., Spearman, J., Hamdan, M. F., D'Costa, C., Blane, C., Giles, M., Peter, M. B., Hirst, N. A., Hossain, T., El-Dhuwaib, A. P. Y., Morrison, T. E. M., Taylor, G. W., Thompson, R. L. E., Mccune, K., Loughlin, P., Lawther, R., Byrnes, C. K., Simpson, D. J., Mawhinney, A., Warren, C., Mckay, D., Mcilmunn, C., Martin, S., Macartney, M., Diamond, T., Davey, P., Jones, C., Clements, J. M., Digney, R., Chan, W. M., Mccain, S., Gull, S., Janeczko, A., Dorrian, E., Harris, A., Dawson, S., Johnston, D., Mcaree, B., Ghareeb, E., Thomas, G., Connelly, M., Mckenzie, S., Cieplucha, K., Spence, G., Campbell, W., Hooks, G., Bradley, N., Hill, A. D. K., Cassidy, J. T., Boland, M., Burke, P., Nally, D. M., Khogali, E., Shabo, W., Iskandar, E., Mcentee, G. P., O'Neill, M. A., Peirce, C., Lyons, E. M., O'Sullivan, A. W., Thakkar, R., Carroll, P., Ivanovski, I., Balfe, P., Lee, M., Winter, D. C., Kelly, M. E., Hoti, E., Maguire, D., Karunakaran, P., Geoghegan, J. G., Mcdermott, F., Martin, S. T., Cross, K. S., Cooke, F., Zeeshan, S., Murphy, J. O., Mealy, K., Mohan, H. M., Nedujchelyn, Y., Ullah, M. F., Ahmed, I., Giovinazzo, F., Milburn, J., Prince, S., Brooke, E., Buchan, J., Khalil, A. M., Vaughan, E. M., Ramage, M. I., Aldridge, R. C., Gibson, S., Nicholson, G. A., Vass, D. G., Grant, A. J., Holroyd, D. J., Angharad Jones, M., Sutton, C. M. L. R., O'Dwyer, P., Nilsson, F., Weber, B., Williamson, T. K., Lalla, K., Bryant, A., Ross Carter, C., Forrest, C. R., Hunter, D. I., Nassar, A. H., Orizu, M. N., Knight, K., Qandeel, H., Suttie, S., Belding, R., Mcclarey, A., Boyd, A. T., Guthrie, G. J. K., Lim, P. J., Luhmann, A., Watson, A. J. M., Richards, C. H., Nicol, L., Madurska, M., Harrison, E., Boyce, K. M., Roebuck, A., Ferguson, G., Pati, P., Wilson, M. S. J., Dalgaty, F., Fothergill, L., Driscoll, P. J., Mozolowski, K. L., Banwell, V., Bennett, S. P., Rogers, P. N., Skelly, B. L., Rutherford, C. L., Mirza, A. K., Lazim, T., Lim, H. C. C., Duke, D., Ahmed, T., Beasley, W. D., Wilkinson, M. D., Maharaj, G., Malcolm, C., Brown, T. H., Al-Sarireh, B., Shingler, G. M., Mowbray, N., Radwan, R., Morcous, P., Wood, S., Kadhim, A., Stewart, D. J., Baker, A. L., Tanner, N., Shenoy, H., Hafiz, S., De Marchi, J. A., Singh-Ranger, D., Hisham, E., Ainley, P., John Terrace, S. O. N., Napetti, S., Hopwood, B., Rhys, T., Downing, J., Kanavati, O., Coats, M., Aleksandrov, D., Kallaway, C., Yahya, S., Templeton, A., Trotter, M., Lo, C., Dhillon, A., Heywood, N., Aawsaj, Y., Hamdan, A., Reece-Bolton, O., Mcguigan, A., Shahin, Y., Aymon, Luther, A. A., Nicholson, J. A., Rajendran, I., Boal, M., and Ritchie, J.

Subjects
Adult, Male, operative difficulty, medicine.medical_specialty, MEDLINE, cholecystectomy, difficulty grading, laparoscopic, Surgery, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Internal medicine, medicine, Humans, Prospective Studies, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Laparoscopic cholecystectomy, Aged, business.industry, General surgery, Correction, Hepatology, Length of Stay, Middle Aged, Conversion to Open Surgery, Cholecystectomy, Laparoscopic, ROC Curve, 030220 oncology & carcinogenesis, Multivariate Analysis, 030211 gastroenterology & hepatology, Female, business, Grading scale, Abdominal surgery
Abstract

A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets.Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall's tau for dichotomous variables, or Jonckheere-Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis.A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p 0.001).We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty.

Published
2018

32. Fatal haemorrhage and incomplete block to embryogenesis in mice lacking coagulation factor V

Author

Cui, Jisong, O'Shea, K. Sue, Purkayastha, Anjali, Saunders, Thomas L., and Ginsburg, David

Subjects
Mice as laboratory animals -- Observations, Blood coagulation factors -- Physiological aspects, Embryology -- Observations, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Almost half of the homozygous mice embryos lacking coagulation factor V die on the ninth or tenth embryonic day due to an abnormality in the yolk-sac vasculature. The other 50% of the homozygous mice die within two hours of birth due to massive haemorrhage. Coagulation factor V is important for the stimulation of prothrombin to thrombin, and the study reveals the vital homeostatic function of thrombin besides fibrin clot formation. The genetic deficiency of coagulation factor V causes the congenital bleeding disorder called parahaemophilia.

Published
1996

34. Transplacental RNAi: deciphering gene function in the postimplantation-staged embryo

Author

O'Shea, K. Sue, De Boer, Lisa S., Slawny, Nicole A., and Gratsch, Theresa E.

Subjects
Genetic aspects, Research, Ovum implantation -- Genetic aspects -- Research, Gene silencing -- Research -- Genetic aspects, RNA interference -- Research -- Genetic aspects, Gene targeting -- Research -- Genetic aspects
Abstract

RNAi offers the opportunity to examine the role in postimplantation development of genes that cause preimplantation lethality and to create allelic series of targeted embryos. We have delivered constituitively expressed [...]

Published
2006

35. Population-based cohort study of variation in the use of emergency cholecystectomy for benign gallbladder diseases

Author

Vohra, R. S., Pasquali, S., Kirkham, A. J., Marriott, P., Johnstone, M., Spreadborough, P., Alderson, D., Griffiths, E. A., Fenwick, S., Elmasry, M., Nunes, Q., Kennedy, D., Basit Khan, R., Khan, M. A. S., Magee, C. J., Jones, S. M., Mason, D., Parappally, C. P., Mathur, P., Saunders, M., Jamel, S., Ul Haque, S., Zafar, S., Shiwani, M. H., Samuel, N., Dar, F., Jackson, A., Lovett, B., Dindyal, S., Winter, H., Fletcher, T., Rahman, S., Wheatley, K., Nieto, T., Ayaani, S., Youssef, H., Nijjar, R. S., Watkin, H., Naumann, D., Emeshi, S., Sarmah, P. B., Lee, K., Joji, N., Heath, J., Teasdale, R. L., Weerasinghe, C., Needham, P. J., Welbourn, H., Forster, L., Finch, D., Blazeby, J. M., Robb, W., Mcnair, A. G. K., Hrycaiczuk, A., Charalabopoulos, A., Kadirkamanathan, S., Tang, C. -B., Jayanthi, N. V. G., Noor, N., Dobbins, B., Cockbain, A. J., Nilsen-Nunn, A., de Siqueira, J., Pellen, M., Cowley, J. B., W. -M., Ho, Miu, V., White, T. J., Hodgkins, K. A., Kinghorn, A., Tutton, M. G., Al-Abed, Y. A., Menzies, D., Ahmad, A., Reed, J., Khan, S., Monk, D., Vitone, L. J., Murtaza, G., Joel, A., Brennan, S., Shier, D., Zhang, C., Yoganathan, T., Robinson, S. J., Mccallum, I. J. D., Jones, M. J., Elsayed, M., Tuck, L., Wayman, J., Carney, K., Aroori, S., Hosie, K. B., Kimble, A., Bunting, D. M., Fawole, A. S., Basheer, M., Dave, R. V., Sarveswaran, J., Jones, E., Kendal, C., Tilston, M. P., Gough, M., Wallace, T., Singh, S., Downing, J., Mockford, K. A., Issa, E., Shah, N., Chauhan, N., Wilson, T. R., Forouzanfar, A., Wild, J. R. L., Nofal, E., Bunnell, C., Madbak, K., Rao, S. T. V., Devoto, L., Siddiqi, N., Khawaja, Z., Hewes, J. C., Gould, L., Chambers, A., Urriza Rodriguez, D., Sen, G., Robinson, S., Bartlett, F., Rae, D. M., Stevenson, T. E. J., Sarvananthan, K., Dwerryhouse, S. J., Higgs, S. M., Old, O. J., Hardy, T. J., Shah, R., Hornby, S. T., Keogh, K., Frank, L., Al-Akash, M., Upchurch, E. A., Frame, R. J., Hughes, M., Jelley, C., Weaver, S., Roy, S., Sillo, T. O., Galanopoulos, G., Cuming, T., Cunha, P., Tayeh, S., Kaptanis, S., Heshaishi, M., Eisawi, A., Abayomi, M., Ngu, W. S., Fleming, K., Singh Bajwa, D., Chitre, V., Aryal, K., Ferris, P., Silva, M., Lammy, S., Mohamed, S., Khawaja, A., Hussain, A., Ghazanfar, M. A., Bellini, M. I., Ebdewi, H., Elshaer, M., Gravante, G., Drake, B., Ogedegbe, A., Mukherjee, D., Arhi, C., Giwa Nusrat Iqbal, L., Watson, N. F., Kumar Aggarwal, S., Orchard, P., Villatoro, E., Willson, P. D., Wa, K., Mok, J., Woodman, T., Deguara, J., Garcea, G., Babu, B. I., Dennison, A. R., Malde, D., Lloyd, D., Satheesan, S., Al-Taan, O., Boddy, A., Slavin, J. P., Jones, R. P., Ballance, L., Gerakopoulos, S., Jambulingam, P., Mansour, S., Sakai, N., Acharya, V., Sadat, M. M., Karim, L., Larkin, D., Amin, K., Khan, A., Law, J., Jamdar, S., Smith, S. R., Sampat, K., M O'shea, K., Manu, M., Asprou, F. M., Malik, N. S., Chang, J., Lewis, M., Roberts, G. P., Karavadra, B., Photi, E., Hewes, J., Rodriguez, D., O'Reilly, D. A., Rate, A. J., Sekhar, H., Henderson, L. T., Starmer, B. Z., Coe, P. O., Tolofari, S., Barrie, J., Bashir, G., Sloane, J., Madanipour, S., Halkias, C., Trevatt, A. E. J., Borowski, D. W., Hornsby, J., Courtney, M. J., Virupaksha, S., Seymour, K., Hawkins, H., Bawa, S., Gallagher, P. V., Reid, A., Wood, P., Finch, J. G., Parmar, J., Stirland, E., Gardner-Thorpe, J., Al-Muhktar, A., Peterson, M., Majeed, A., Bajwa, F. M., Martin, J., Choy, A., Tsang, A., Pore, N., Andrew, D. R., Al-Khyatt, W., Taylor, C., Bhandari, S., Subramanium, D., Toh, S. K. C., Carter, N. C., Mercer, S. J., Knight, B., Tate, S., Pearce, B., Wainwright, D., Vijay, V., Alagaratnam, S., Sinha, S., El-Hasani, S. S., Hussain, A. A., Bhattacharya, V., Kansal, N., Fasih, T., Jackson, C., Siddiqui, M. N., Chishti, I. A., Fordham, I. J., Siddiqui, Z., Bausbacher, H., Geogloma, I., Gurung, K., Tsavellas, G., Basynat, P., Kiran Shrestha, A., Basu, S., Chhabra Mohan Harilingam, A., Rabie, M., Akhtar, M., Kumar, P., Jafferbhoy, S. F., Hussain, N., Raza, S., Haque, M., Alam, I., Aseem, R., Patel, S., Asad, M., Booth, M. I., Ball, W. R., Wood, C. P. J., Pinho-Gomes, A. C., Kausar, A., Rami Obeidallah, M., Varghase, J., Lodhia, J., Bradley, D., Rengifo, C., Lindsay, D., Gopalswamy, S., Finlay, I., Wardle, S., Bullen, N., Iftikhar, S. Y., Awan, A., Ahmed, J., Leeder, P., Fusai, G., Bond-Smith, G., Psica, A., Puri, Y., Hou, D., Noble, F., Szentpali, K., Broadhurst, J., Date, R., Hossack, M. R., Li Goh, Y., Turner, P., Shetty, V., Riera, M., Macano, C. A. W., Sukha, A., Preston, S. R., Hoban, J. R., Puntis, D. J., Williams, S. V., Krysztopik, R., Kynaston, J., Batt, J., Doe, M., Goscimski, A., Jones, G. H., Hall, C., Carty, N., Panteleimonitis, S., Gunasekera, R. T., Sheel, A. R. G., Lennon, H., Hindley, C., Reddy, M., Kenny, R., Elkheir, N., Mcglone, E. R., Rajaganeshan, R., Hancorn, K., Hargreaves, A., Prasad, R., Longbotham, D. A., Vijayanand, D., Wijetunga, I., Ziprin, P., Nicolay, C. R., Yeldham, G., Read, E., Gossage, J. A., Rolph, R. C., Ebied, H., Phull, M., Khan, M. A., Popplewell, M., Kyriakidis, D., Henley, N., Packer, J. R., Derbyshire, L., Porter, J., Appleton, S., Farouk, M., Basra, M., Jennings, N. A., Ali, S., Kanakala, V., Ali, H., Lane, R., Dickson-Lowe, R., Zarsadias, P., Mirza, D., Puig, S., Al Amari, K., Vijayan, D., Sutcliffe, R., Marudanayagam, R., Hamady, Z., Prasad, A. R., Patel, A., Durkin, D., Kaur, P., Bowen, L., Byrne, J. P., Pearson, K. L., Delisle, T. G., Davies, J., Tomlinson, M. A., Johnpulle, M. A., Slawinski, C., Macdonald, A., Nicholson, J., Newton, K., Mbuvi, J., Farooq, A., Sidhartha Mothe, B., Zafrani, Z., Brett, D., Francombe, J., Barnes, J., Cheung, M., Al-Bahrani, A. Z., Preziosi, G., Urbonas, T., Alberts, J., Mallik, M., Patel, K., Segaran, A., Doulias, T., Sufi, P. A., Yao, C., Pollock, S., Manzelli, A., Wajed, S., Kourkulos, M., Pezzuto, R., Wadley, M., Hamilton, E., Jaunoo, S., Padwick, R., Sayegh, M., Newton, R. C., Hebbar, M., Farag, S. F., Spearman, J., Hamdan, M. F., D'Costa, C., Blane, C., Giles, M., Peter, M. B., Hirst, N. A., Hossain, T., Pannu, A., El-Dhuwaib, Y., Morrison, T. E. M., Taylor, G. W., Thompson, R. L. E., Mccune, K., Loughlin, P., Lawther, R., Byrnes, C. K., Simpson, D. J., Mawhinney, A., Warren, C., Mckay, D., Mcilmunn, C., Martin, S., Macartney, M., Diamond, T., Davey, P., Jones, C., Clements, J. M., Digney, R., Chan, W. M., Mccain, S., Gull, S., Janeczko, A., Dorrian, E., Harris, A., Dawson, S., Johnston, D., Mcaree, B., Ghareeb, E., Thomas, G., Connelly, M., Mckenzie, S., Cieplucha, K., Spence, G., Campbell, W., Hooks, G., Bradley, N., Hill, A. D. K., Cassidy, J. T., Boland, M., Burke, P., Nally, D. 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Subjects
Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Gallbladder disease, Population, Gallbladder Diseases, 030230 surgery, Biliary colic, Time-to-Treatment, 03 medical and health sciences, 0302 clinical medicine, Emergency cholecystectomy, benign gallbladder disease, hospital care, 80 and over, Medicine, Humans, Cholecystectomy, Prospective Studies, Prospective cohort study, education, Emergency Treatment, Aged, Aged, 80 and over, education.field_of_study, Endoscopic retrograde cholangiopancreatography, medicine.diagnostic_test, business.industry, General surgery, Gallbladder, Middle Aged, medicine.disease, Hospitals, United Kingdom, Hospitalization, medicine.anatomical_structure, Centre for Surgical Research, 030220 oncology & carcinogenesis, Female, Ireland, Surgery, medicine.symptom, business, Cohort study
Abstract

Background The aims of this prospective population-based cohort study were to identify the patient and hospital characteristics associated with emergency cholecystectomy, and the influences of these in determining variations between hospitals. Methods Data were collected for consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing the performance of emergency cholecystectomy were analysed by means of multilevel, multivariable logistic regression modelling using a two-level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 4744 cholecystectomies from 165 hospitals. Increasing age, lower ASA fitness grade, biliary colic, the need for further imaging (magnetic retrograde cholangiopancreatography), endoscopic interventions (endoscopic retrograde cholangiopancreatography) and admission to a non-biliary centre significantly reduced the likelihood of an emergency cholecystectomy being performed. The multilevel model was used to calculate the probability of receiving an emergency cholecystectomy for a woman aged 40 years or over with an ASA grade of I or II and a BMI of at least 25·0 kg/m2, who presented with acute cholecystitis with an ultrasound scan showing a thick-walled gallbladder and a normal common bile duct. The mean predicted probability of receiving an emergency cholecystectomy was 0·52 (95 per cent c.i. 0·45 to 0·57). The predicted probabilities ranged from 0·02 to 0·95 across the 165 hospitals, demonstrating significant variation between hospitals. Conclusion Patients with similar characteristics presenting to different hospitals with acute gallbladder pathology do not receive comparable care.

Published
2016
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36. Use of selected scavengers for the determination of NF-TiO2 reactive oxygen species during the degradation of microcystin-LR under visible light irradiation

Author

Pelaez, M. Falaras, P. Likodimos, V. O'Shea, K. de la Cruz, A.A. Dunlop, P.S.M. Byrne, J.A. Dionysiou, D.D.

Abstract

Although UV-induced TiO2 photocatalysis involves the generation of several reactive oxygen species (ROS), the formation of hydroxyl radicals is generally associated with the degradation of persistent organic contaminants in water. In this study, a variety of radical scavengers were employed to discriminate the roles of different ROS during visible light-activated (VLA) photocatalysis using nitrogen and fluorine doped TiO2 (NF-TiO2) in the degradation of the hepatotoxin, microcystin-LR (MC-LR) in water. The addition of hydroxyl radical scavengers, methanol and tert-butyl alcohol to the reaction mixture resulted in negligible inhibition of NF-TiO2 photocatalytic degradation of MC-LR at pH 3.0 and only partial inhibition at pH 5.7 under visible light. While hydroxyl radicals ([rad]OH) generally play the primary role in UV-TiO2 photocatalysis, the minimal influence of MeOH and t-BuOH on the degradation process under these experimental conditions indicates that [rad]OH are not crucial in VLA NF-TiO2 photocatalysis. However, strong inhibition was observed in VLA NF-TiO2 photocatalytic degradation of MC-LR in the presence of superoxide dismutase, benzoquinone and catalase at pH 3.0 and 5.7 indicating that O2[rad]− and H2O2 play critical roles in the degradation process. Similar degradation rates were observed in the presence of deuterium oxide, which enhances singlet oxygen mediated processes further suggesting singlet oxygen is not a key species in the degradation of MC-LR. Formic acid and cupric nitrate were added to probe the roles of the valence band holes and conduction band electrons, respectively. Under UV–vis light irradiation, almost complete inhibition of MC-LR removal is observed with NF-TiO2 in the presence of [rad]OH scavengers at pH 5.7. These results demonstrate that the solution pH plays a major role in the formation and reactivity of ROS during VLA NF-TiO2 photocatalysis. The adsorption strength of scavengers and MC-LR onto NF-TiO2 as well as the speciation of ROS as a function of pH needs to be carefully considered since they also play a major role in the efficiency of the process. These results indicate that the reduction of molecular oxygen by photo-generated electrons rather than hydroxyl radicals produced by oxidative reactions of photo-generated holes is the key factor in the VLA NF-TiO2 photocatalytic degradation of MC-LR. © 2016 Elsevier B.V.

Published
2016

38. Investigating the effects of contacting functional oxide films

Author

O'Shea, K. J., Homonnay, N., Schmidt, G, and MacLaren, D. A.

Abstract

Advanced oxides are the current focus of intense research activity, driven by their numerous attractive properties for next generation microelectronics. However, reliable strategies must be developed for the electrical contacting of such films without compromising their functionality. We explore the effect of depositing both noble and oxidising metals onto the ferromagnetic La0.7Sr0.3MnO3 (LSMO) in terms of its structural and magnetic properties. Whilst noble metal overlayers have negligible impact, the metals typically used as adhesion layers, such as Ti, can drive a structural phase transition in the LSMO, producing a Brownmillerite phase and impairing the magnetisation.

Published
2015

39. Concentric 360° domain wall nesting in magnetic tunnel junction films: a Lorentz TEM study

Author

O'Shea, K., Rode, K., Kurt, H., McGrouther, D., and MacLaren, D.A.

Abstract

We describe the formation of an unusual concentric magnetic domain wall pattern in the free layer of a bottom pinned magnetic tunnel junction. Lorentz microscopy reveals that repeated switching of the free layer with a magnetic field applied perpendicular to the exchange bias direction can produce a series of concentric 360° domain wall loops, a phenomenon we refer to as domain wall nesting. We propose two necessary ingredients for the behaviour: (i) inhomogeneities in the grain-by-grain magnetic dispersion that break local symmetry to produce a preferential sense of magnetic rotation upon field switching; and (ii) structural defects that act to pin 360° domain walls. Further control of this behaviour may provide new functionality for future device applications.

Published
2015

41. Erratum: “Seed layer technique for high quality epitaxial manganite films” [AIP Advances 6, 085109 (2016)]

Author

Graziosi, P., primary, Gambardella, A., additional, Calbucci, M., additional, O’Shea, K., additional, MacLaren, D. A., additional, Riminucci, A., additional, Bergenti, I., additional, Fugattini, S., additional, Prezioso, M., additional, Homonnay, N., additional, Schmidt, G., additional, Pullini, D., additional, Busquets-Mataix, D., additional, and Dediu, V., additional

Published
2016
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42. Seed layer technique for high quality epitaxial manganite films

Author

Graziosi, P., primary, Gambardella, A., additional, Calbucci, M., additional, O’Shea, K., additional, MacLaren, D. A., additional, Riminucci, A., additional, Bergenti, I., additional, Fugattini, S., additional, Prezioso, M., additional, Homonnay, N., additional, Schmidt, G., additional, Pullini, D., additional, Busquets-Mataix, D., additional, and Dediu, V., additional

Published
2016
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44. Investigating the effect of a stress-based uniaxial anisotropy on the magnetic behaviour of La0.7Sr0.3MnO3 elements

Author

O'Shea, K. J., Bova, K., McGrouther, D., and MacLaren, D. A.

Abstract

We investigate the interplay between shape anisotropy and a stress-based uniaxial anisotropy on the magnetic domain structure of La0.7Sr0.3MnO3 nanoelements as a function of aspect ratio, using micromagnetic simulations. We show that a direct competition between the anisotropies gives rise to high energy multi-domain flux closure configurations, whilst an alignment of the anisotropies can modify the effective element dimensions and act to stabilise a single domain configuration. Our results demonstrate the ability to control the spin state of La0.7Sr0.3MnO3 elements in addition to tailoring the domain wall width by controlling the anisotropy of the material, which is key for spintronic applications that require a high spin-polarization and stable magnetic configurations.

Published
2014

49. Towards a New Generation of Conversational Agents Based on Sentence Similarity

Author

O'Shea, K, Bandar, Z, and Crockett, KA

Abstract

The Conversational Agent (CA) is a computer program that can engage in conversation using natural language dialogue with a human participant. Most CAs employ a pattern-matching technique to map user input onto structural patterns of sentences. However, every combination of utterances that a user may send as input must be taken into account when constructing such a script. This chapter was concerned with constructing a novel CA using sentence similarity measures. Examining word meaning rather than structural patterns of sentences meant that scripting was reduced to a couple of natural language sentences per rule as opposed to potentially 100s of patterns. Furthermore, initial results indicate good sentence similarity matching with 13 out of 18 domain-specific user utterances as opposed to that of the traditional pattern matching approach.

Published
2008

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