141 results on '"O'Shea R"'
Search Results
2. The gas grid as a vector for regional decarbonisation - a techno economic case study for biomethane injection and natural gas heavy goods vehicles
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Keogh, Niamh, Corr, D., O'Shea, R., and Monaghan, R.F.D.
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- 2022
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3. Implications of European Union recast Renewable Energy Directive sustainability criteria for renewable heat and transport: Case study of willow biomethane in Ireland
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Long, A., Bose, A., O'Shea, R., Monaghan, R., and Murphy, J.D.
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- 2021
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4. The ALERT-B questionnaire: A screening tool for the detection of gastroenterological late effects after radiotherapy for prostate cancer
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Farnell, D.J.J., Staffurth, J., Sivell, S., Ahmedzai, S., Andreyev, J., Green, J., Sanders, D.S., Ferguson, C.J., Pickett, S., Muls, A., O'Shea, R., Campbell, S.H., Taylor, S.E., and Nelson, A.
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- 2020
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5. Intracellular lipid droplet accumulation occurs early following viral infection and is required for an efficient interferon response
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Monson, E. A., Crosse, K. M., Duan, M., Chen, W., O’Shea, R. D., Wakim, L. M., Carr, J. M., Whelan, D. R., and Helbig, K. J.
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- 2021
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6. Kynurenine pathway metabolism and the neurobiology of treatment-resistant depression: Comparison of multiple ketamine infusions and electroconvulsive therapy
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Allen, A.P., Naughton, M., Dowling, J., Walsh, A., O'Shea, R., Shorten, G., Scott, L., McLoughlin, D.M., Cryan, J.F., Clarke, G., and Dinan, T.G.
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- 2018
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7. An energy and greenhouse gas comparison of centralised biogas production with road haulage of pig slurry, and decentralised biogas production with biogas transportation in a low-pressure pipe network
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O'Shea, R., Wall, D.M., and Murphy, J.D.
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- 2017
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8. The potential of power to gas to provide green gas utilising existing CO2 sources from industries, distilleries and wastewater treatment facilities
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O'Shea, R., Wall, D.M., McDonagh, S., and Murphy, J.D.
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- 2017
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9. Modelling a demand driven biogas system for production of electricity at peak demand and for production of biomethane at other times
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O’Shea, R., Wall, D., and Murphy, J.D.
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- 2016
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10. Investigating two-phase digestion of grass silage for demand-driven biogas applications: Effect of particle size and rumen fluid addition
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Wall, D.M., Allen, E., O'Shea, R., O'Kiely, P., and Murphy, J.D.
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- 2016
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11. Next generation sequencing is informing phenotype: a TP53 example
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O’Shea, R., Clarke, R., Berkley, E., Giffney, C., Farrell, M., O’Donovan, E., and Gallagher, D. J.
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- 2017
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12. Dynamic response signatures of a scaled model platform for floating wind turbines in an ocean wave basin
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Jaksic, V., O'Shea, R., Cahill, P., Murphy, J., Mandic, D. P., and Pakrashi, V.
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- 2015
13. Safety of elective paediatric surgery during the coronavirus disease 2019 pandemic
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Kavanagh, F.G., primary, James, D.L., additional, Brinkman, D., additional, Cornyn, S., additional, Murphy, C., additional, O'Neill, S., additional, O'Shea, R., additional, Affendi, A., additional, Lang, B., additional, O'Connor, A., additional, Keogh, I., additional, Lang, E., additional, Russell, J., additional, O'Brien, D., additional, Sheahan, P., additional, Kang, So Jeong, additional, O'Sullivan, Ryan, additional, Kennedy, Brian, additional, Tiernan, Conor, additional, Murchú, Oisín ó, additional, Urbaniak, Agnieska, additional, Hannon, Colm, additional, O'Sullivan, Peter, additional, Khan, Habib, additional, Dias, Andrew, additional, Coakley, Darragh, additional, Mehanna, Rania, additional, Hone, Stephen, additional, Garry, Stephen, additional, Heffernan, Coleen, additional, Phelan, Eimear, additional, Kieran, Stephen, additional, Boyle, Seamus, additional, Fitzsimons, Michael, additional, Young, Orla, additional, Thornton, Mona, additional, Lang, John, additional, Gormley, Peter, additional, Subramaniam, Thavakumar, additional, Aly, Moustafa, additional, Zaman, Tahir, additional, Majeed, Khalid, additional, Fapohunda, Ola, additional, Byrne, Ross, additional, Cregg, Joanne, additional, Cheema, Jesvin, additional, Thornton, David, additional, O'Domhaill, Oisin, additional, Donnelly, Martin, additional, Smith, David, additional, Skinner, Liam, additional, and Mahesh, Bangalore, additional
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- 2021
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14. Hematologic abnormalities as a marker of cirrhosis after Fontan completion
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Scandinaro, A, primary, Haider, M, additional, Saef, J, additional, Farwati, M, additional, Allende, D, additional, Ghobrial, J, additional, Zahka, K, additional, O'Shea, R, additional, and Fares, M, additional
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- 2021
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15. Offshore Multi-use setting: Introducing integrative assessment modelling to alleviate uncertainty of developing Seaweed Aquaculture inside Wind Farms
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O'Shea, R, Collins, A, and Howe, C
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History ,Global and Planetary Change ,Environmental Engineering ,Polymers and Plastics ,Business and International Management ,Management, Monitoring, Policy and Law ,Pollution ,Waste Management and Disposal ,Industrial and Manufacturing Engineering - Abstract
The offshore multi-use setting is a concept that reduces spatial competition in the marine economy. Seaweed Aquaculture inside Wind Farms has been suggested as a multi-use setting design, however, the uncertainty surrounding impacts associated with multi-use setting activities is a key barrier to the development of the concept. To begin alleviating uncertainty on the Seaweed Aquaculture-Wind Farm system, a systematic literature review was performed to identify the potential negative consequences of developing seaweed aquaculture inside of Wind Farms. Findings suggest negative consequences may result across multiple objectives. The study findings were used to construct cognitive models that are necessary to facilitate further integrative assessment modelling on social and ecological impacts of integrating seaweed aquaculture and Wind Farms. The interdisciplinary frameworks and research strategy proposed by this study is the first attempt to formalise holistic sustainability assessment and novel management of an emerging bioeconomic innovation being pursued in Europe
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- 2022
16. Psychomotor stimulant effects of α-pyrrolidinovalerophenone (αPVP) enantiomers correlate with drug binding kinetics at the dopamine transporter
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Stockner T, Alexander F. Hoffman, Schwazer J, Sandtner W, Pollak D, Harald H. Sitte, Kathrin Jäntsch, O'Shea R, Marco Niello, Gradisch R, Carl R. Lupica, Julian Maier, Sideromenos S, and Michael H. Baumann
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Drug ,Psychomotor learning ,biology ,Chemistry ,media_common.quotation_subject ,medicine.medical_treatment ,Pharmacology ,Receptor–ligand kinetics ,Stimulant ,medicine ,biology.protein ,Enantiomer ,media_common ,Dopamine transporter - Abstract
α-Pyrrolidinovalerophenone (αPVP) is a psychostimulant and drug of abuse associated with severe intoxications in humans. αPVP exerts long-lasting psychostimulant effects, when compared to the classical dopamine transporter (DAT) inhibitor cocaine. Here, we compared the two enantiomeric forms of αPVP, the R- and the S-αPVP, with cocaine using a combination of in silico, in vitro and in vivo approaches. We found that αPVP enantiomers substantially differ from cocaine in their binding kinetics. The two enantiomers differ from each other in their association rates. However, they show similar slow dissociation rates leading to pseudo-irreversible binding kinetics at DAT. The pseudo-irreversible binding kinetics of αPVP is responsible for the observed non-competitive pharmacology and it correlates with persistent psychostimulant effects in mice. Thus, the slow binding kinetics of αPVP enantiomers profoundly differ from the fast kinetics of cocaine both in vitro and in vivo, suggesting drug-binding kinetics as a potential driver of psychostimulant effects in vivo.
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- 2021
17. 1283P Predicting PD-L1 expression using [18F]FDG PET/CT in early stage non-small cell lung cancer (NSCLC)
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Hughes, D.J., Josephides, E., O'Shea, R., Manickavasagar, T., Horst, C., Hunter, S., Taniere, P., Nonaka, D., Spicer, J., Goh, V., Bille, A., Karapanagiotou, E.M., and Cook, G.
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- 2023
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18. No protective order action against retirement community
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O'Shea, R.
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Restraining orders -- Laws, regulations and rules ,Depositions -- Laws, regulations and rules ,Government regulation ,Law ,News, opinion and commentary - Abstract
Byline: roshea Where plaintiff seeks to depose a representative of defendant Hickory Hill Retirement Community, defendant's motion for a protective order regarding some of the deposition topics is denied. Decision [...]
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- 2020
19. How can Australia integrate routine genetic sequencing in oncology: a qualitative study through an implementation science lens
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O'Shea, R, Rankin, NM, Kentwell, M, Gleeson, M, Salmon, L, Tucker, KM, Lewis, S, and Taylor, N
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Genetics & Heredity ,0604 Genetics, 1103 Clinical Sciences ,Australia ,Humans ,Breast Neoplasms ,Genetic Testing ,Qualitative Research ,Implementation Science - Abstract
PurposeThis study sought to determine genetics and oncology specialists' views of integrating BRCA1 and BRCA2 testing in epithelial ovarian and breast cancer into routine practice.MethodsQualitative interviews were designed using the Consolidated Framework for Implementation Research. Questions included experiences or views of the BRCA testing processes, implementation needs of oncology health professionals, perceived challenges, and future ideas for interventions to integrate genetic testing into oncology.ResultsTwenty-two participants were interviewed from twelve health organizations and four themes were identified: (1) embracing the shift to mainstream genetic testing, with the majority of participants viewing BRCA testing as clinically useful and routine use important for maintaining a patient centered process; (2) the need for communication networks and role delineation to integrate routine genetic testing; (3) factors that influence sustaining routine genetic testing, including ongoing training, resources and funding, real-world adaptation, system complexity, and champions; and (4) variation in system interventions for integrating routine genetic testing align to organizational context.ConclusionFindings illustrate the need for integrating genetic testing into routine oncology, and that adaptation of interventions and processes is essential to sustain a feasible model. An understanding of individual and organizational implementation factors will help to prepare for future integration of routine genetic testing in other cancers.
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- 2020
20. Online BRCA1/2 screening in the Australian Jewish community: a qualitative study
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Yuen, J, Cousens, N, Barlow-Stewart, K, O'Shea, R, and Andrews, L
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0604 Genetics - Abstract
Screening programmes for BRCA1/2 Jewish Founder mutations (JFM) in the Jewish community have been advocated internationally. Implementation of these programmes could decrease morbidity and mortality of BRCA1/2 JFM carriers through the uptake of cancer screening strategies and risk-reducing surgery. An online programme offered to the Sydney Jewish community that delivers pre-test information and collects consent for BRCA1/2 JFM testing via a website is currently being evaluated (JeneScreen). Forty-three participants from JeneScreen were invited to participate in a sub-study, of semi-structured pre- and post-result telephone interviews. Eleven participants consented to the sub-study. The interviews explored their experiences regarding the online model of obtaining pre-test genetic information, giving consent and receiving results. Inductive thematic analysis was carried out on the interviews. Overarching themes identified include (1) embracing online testing, (2) the online pre-test experience, (3) the result notification experience, (4) concerns associated with online testing and (5) testing as a responsibility. Overall, participants were highly satisfied with online BRCA1/2 JFM testing, an indication that the a website for pre-test information provision is an acceptable alternative to in-person genetic counselling for BRCA1/2 JFM screening and represents a feasible model for future community screening efforts.
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- 2019
21. Finding Diagnostically Useful Patterns in Quantitative Phenotypic Data
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Aitken, Stuart, primary, Firth, Helen V., additional, McRae, Jeremy, additional, Halachev, Mihail, additional, Kini, Usha, additional, Parker, Michael J., additional, Lees, Melissa M., additional, Lachlan, Katherine, additional, Sarkar, Ajoy, additional, Joss, Shelagh, additional, Splitt, Miranda, additional, McKee, Shane, additional, Németh, Andrea H., additional, Scott, Richard H., additional, Wright, Caroline F., additional, Marsh, Joseph A., additional, Hurles, Matthew E., additional, FitzPatrick, David R., additional, Fitzgerald, T.W., additional, Gerety, S.S., additional, Jones, W.D., additional, van Kogelenberg, M., additional, King, D.A., additional, McRae, J., additional, Morley, K.I., additional, Parthiban, V., additional, Al-Turki, S., additional, Ambridge, K., additional, Barrett, D.M., additional, Bayzetinova, T., additional, Clayton, S., additional, Coomber, E.L., additional, Gribble, S., additional, Jones, P., additional, Krishnappa, N., additional, Mason, L.E., additional, Middleton, A., additional, Miller, R., additional, Prigmore, E., additional, Rajan, D., additional, Sifrim, A., additional, Tivey, A.R., additional, Ahmed, M., additional, Akawi, N., additional, Andrews, R., additional, Anjum, U., additional, Archer, H., additional, Armstrong, R., additional, Balasubramanian, M., additional, Banerjee, R., additional, Barelle, D., additional, Batstone, P., additional, Baty, D., additional, Bennett, C., additional, Berg, J., additional, Bernhard, B., additional, Bevan, A.P., additional, Blair, E., additional, Blyth, M., additional, Bohanna, D., additional, Bourdon, L., additional, Bourn, D., additional, Brady, A., additional, Bragin, E., additional, Brewer, C., additional, Brueton, L., additional, Brunstrom, K., additional, Bumpstead, S.J., additional, Bunyan, D.J., additional, Burn, J., additional, Burton, J., additional, Canham, N., additional, Castle, B., additional, Chandler, K., additional, Clasper, S., additional, Clayton-Smith, J., additional, Cole, T., additional, Collins, A., additional, Collinson, M.N., additional, Connell, F., additional, Cooper, N., additional, Cox, H., additional, Cresswell, L., additional, Cross, G., additional, Crow, Y., additional, D’Alessandro, P.M., additional, Dabir, T., additional, Davidson, R., additional, Davies, S., additional, Dean, J., additional, Deshpande, C., additional, Devlin, G., additional, Dixit, A., additional, Dominiczak, A., additional, Donnelly, C., additional, Donnelly, D., additional, Douglas, A., additional, Duncan, A., additional, Eason, J., additional, Edkins, S., additional, Ellard, S., additional, Ellis, P., additional, Elmslie, F., additional, Evans, K., additional, Everest, S., additional, Fendick, T., additional, Fisher, R., additional, Flinter, F., additional, Foulds, N., additional, Fryer, A., additional, Fu, B., additional, Gardiner, C., additional, Gaunt, L., additional, Ghali, N., additional, Gibbons, R., additional, Pereira, S.L. Gomes, additional, Goodship, J., additional, Goudie, D., additional, Gray, E., additional, Greene, P., additional, Greenhalgh, L., additional, Harrison, L., additional, Hawkins, R., additional, Hellens, S., additional, Henderson, A., additional, Hobson, E., additional, Holden, S., additional, Holder, S., additional, Hollingsworth, G., additional, Homfray, T., additional, Humphreys, M., additional, Hurst, J., additional, Ingram, S., additional, Irving, M., additional, Jarvis, J., additional, Jenkins, L., additional, Johnson, D., additional, Jones, D., additional, Jones, E., additional, Josifova, D., additional, Joss, S., additional, Kaemba, B., additional, Kazembe, S., additional, Kerr, B., additional, Kini, U., additional, Kinning, E., additional, Kirby, G., additional, Kirk, C., additional, Kivuva, E., additional, Kraus, A., additional, Kumar, D., additional, Lachlan, K., additional, Lam, W., additional, Lampe, A., additional, Langman, C., additional, Lees, M., additional, Lim, D., additional, Lowther, G., additional, Lynch, S.A., additional, Magee, A., additional, Maher, E., additional, Mansour, S., additional, Marks, K., additional, Martin, K., additional, Maye, U., additional, McCann, E., additional, McConnell, V., additional, McEntagart, M., additional, McGowan, R., additional, McKay, K., additional, McKee, S., additional, McMullan, D.J., additional, McNerlan, S., additional, Mehta, S., additional, Metcalfe, K., additional, Miles, E., additional, Mohammed, S., additional, Montgomery, T., additional, Moore, D., additional, Morgan, S., additional, Morris, A., additional, Morton, J., additional, Mugalaasi, H., additional, Murday, V., additional, Nevitt, L., additional, Newbury-Ecob, R., additional, Norman, A., additional, O’Shea, R., additional, Ogilvie, C., additional, Park, S., additional, Parker, M.J., additional, Patel, C., additional, Paterson, J., additional, Payne, S., additional, Phipps, J., additional, Pilz, D.T., additional, Porteous, D., additional, Pratt, N., additional, Prescott, K., additional, Price, S., additional, Pridham, A., additional, Proctor, A., additional, Purnell, H., additional, Ragge, N., additional, Rankin, J., additional, Raymond, L., additional, Rice, D., additional, Robert, L., additional, Roberts, E., additional, Roberts, G., additional, Roberts, J., additional, Roberts, P., additional, Ross, A., additional, Rosser, E., additional, Saggar, A., additional, Samant, S., additional, Sandford, R., additional, Sarkar, A., additional, Schweiger, S., additional, Scott, C., additional, Scott, R., additional, Selby, A., additional, Seller, A., additional, Sequeira, C., additional, Shannon, N., additional, Sharif, S., additional, Shaw-Smith, C., additional, Shearing, E., additional, Shears, D., additional, Simonic, I., additional, Simpkin, D., additional, Singzon, R., additional, Skitt, Z., additional, Smith, A., additional, Smith, B., additional, Smith, K., additional, Smithson, S., additional, Sneddon, L., additional, Splitt, M., additional, Squires, M., additional, Stewart, F., additional, Stewart, H., additional, Suri, M., additional, Sutton, V., additional, Swaminathan, G.J., additional, Sweeney, E., additional, Tatton-Brown, K., additional, Taylor, C., additional, Taylor, R., additional, Tein, M., additional, Temple, I.K., additional, Thomson, J., additional, Tolmie, J., additional, Torokwa, A., additional, Treacy, B., additional, Turner, C., additional, Turnpenny, P., additional, Tysoe, C., additional, Vandersteen, A., additional, Vasudevan, P., additional, Vogt, J., additional, Wakeling, E., additional, Walker, D., additional, Waters, J., additional, Weber, A., additional, Wellesley, D., additional, Whiteford, M., additional, Widaa, S., additional, Wilcox, S., additional, Williams, D., additional, Williams, N., additional, Woods, G., additional, Wragg, C., additional, Wright, M., additional, Yang, F., additional, Yau, M., additional, Carter, N.P., additional, Parker, M., additional, Firth, H.V., additional, FitzPatrick, D.R., additional, Wright, C.F., additional, Barrett, J.C., additional, and Hurles, M.E., additional
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- 2019
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22. The Impact of Specialized Gastroenterology Services for Late Pelvic Radiation Disease: Results from the Prospective Multicenter EAGLE Study
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Staffurth, J., primary, Sivell, S., additional, Ahmedzai, S., additional, Andreyev, J., additional, Farnell, D., additional, Green, J., additional, Sanders, D., additional, Ferguson, C.L., additional, Pickett, S., additional, Smith, L., additional, Cohen, D., additional, O'Shea, R., additional, Campbell, S., additional, Taylor, S., additional, and Nelson, A., additional
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- 2018
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23. S02. The Next Step in Cardiac Genetics: Targeted gene panels and next generation sequencing in inherited cardiac conditions
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Deeny, HA, Murphy, AM, O'Rourke, D, Gallagher, S, Rea, G, Ware, JS, Lightman, EG, Walsh, R, John, S, Homfray, T, Till, J, Prasad, S, Buchan, R, Wilkinson, S, Barton, PJR, Cook, SA, McVeigh, TP, Cody, N, Meany, M, Carroll, C, O'Shea, R, Gallagher, DJ, Clabby, C, Green, AJ, Casey, J, Crushell, E, Hughes, J, Losty, E, Slattery, D, Green, A, Ennis, S, Lynch, SA, Kirk, CW, McKee, S, Project, DDD, Al Shehhi, M, Shen, S, Gallagher, L, Betts, DR, McArdle, L, Quinn, EM, Coleman, C, Molloy, B, Dominguez Castro, P, Trimble, V, Mahmud, N, McManus, R, Jung, S, Salzman, D, Kerin, MJ, Nallur, S, Dookwah, M, Nemec, AA, Sadofsky, J, Paranjape, T, Kelly, O, Chan, E., Miller, N, Sweeney, KJ, Zelterman, D, Sweasy, J, Pilarski, R, Telesca, D, Weidhaas, JB, Stapleton, CP, McCormack, M, Connaughton, D, Phelan, PJ, Cavalleri, GL, Conlon, PJ, Gilbert, E, O'Reilly, S, Merrigan, M, McGettigan, D, Cavalleri, G, Heavin, SB, Slattery, L, Walley, N, Avbersek, A, Novy, J, Sinha, S, Alarts, N, Legros, B, Radtke, R, Doherty, C, Depondt, C, Sisodiya, S, Goldstein, D, Delanty, N, Nesbit, MA, Courtney, DG, Allen, EHA, Atkinson, SD, Maurizi, E, Moore, JE, Pedrioli, DM Leslie, McLean, WHI, Moore, CBT, Petyrka, J, Vieira, M, Donnelly, DE, O'Neill, T, Hardy, R, Morrison, PJ, Hegarty, M, Irvine, M, Dabir, T, Zhang, X, Dineen, T, Flanagan, J, Kovacs, A, Mihart, R, O'Callaghan, J, Culligan, J, Daly, N, McAuliffe, D, Waterstone, J, Owens, P, Guerin, C, Quill, D, Bell, M, Lowery, AJ, Bradley, L, Barton, DE, Matthews, J, Turner, J, O'Byrne, JJ, Fitzsimons, PE, Unger, S, Croft, J, Mayne, PD, Moylette, E, McDonnell, C, Parker, VE, Al-Shehhi, M, Kelly, PM, Costigan, C, Hegarty, A, Knox, R, Byrne, S, Semple, LRK., Irvine, A, McDaid, J, Ryan, H, Dunne, A, Lambert, DM, Treacy, EP, Lynch, SM, McKenna, MM, Walsh, CP, McKenna, DJ, Whitton, L, Cosgrove, D, Clarkson, C, Gill, M, Corvin, A, Rea, S, Donohoe, G, Morris, D, Neville, J, Ryan, AM, Hand, CK, Ryan, E, Ryan, F, Barton, D, O'Dwyer, V, Neylan, D, Nesbitt, H, Byrne, NM, Worthington, J, Mc Keown, SR, Mc Kenna, DJ, Harold, D, Holland, J, Mothershill, O, Allen, EH, Leslie Pedrioli, DM, Courtney, D, Cole, A, Cox, S, Jeong, C, Droma, Y, Hanaoka, M, Ota, M, Gasparini, P, Montgomery, H, Di Rienzo, A, Robbins, P, L. Cavalleri, G, Heavin, S, Buckley, P, Irwin, RE, Thakur, A, O’ Neill, KM, Cummins, Paul, Mackin, SJ, O'Neill, K, Walsh, C, Schiroli, D, Mulligan, R, Sebag, F, Ozaki, M, Molloy, AM, Mills, JL, Fan, R, Wang, Y, Gibney, ER, Shane, B, Brody, LC, Parle-Mcdermott, A, O'Halloran, ET, Ebrahim, A, Meydan, C, Mason, C, and Magalhães, TR
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Poster Presentations ,Abstracts ,Programme ,Spoken Papers - Abstract
Aims The Irish DNA Atlas is a DNA collection being assembled with the aim of describing the fine-scale population structure in Ireland. Understanding such structure can inform on optimal design of clinical genetic studies as well as the history of the Irish population. We will present an overview of and the preliminary findings from the study. Methods We are recruiting individuals with all eight greatgrandparents born in Ireland, within 30 kilometres of each other. Participants are asked to complete a detailed birth-brief, which records place and date of birth of three generations of ancestors. We also collect some basic health-related details. DNA is extracted from a saliva sample. We have genotyped using an Illumina OmniExpressdense SNP genotyping platform. We present a number of analyses designed to visualise genetic structure, including; Principle Component, ADMIXTURE, and Runs of Homozygosity analysis. Results To date we have recruited 162 participants. The mean great-grandparental area is 32 kilometres, with an average greatgrandparental date of birth of 1850. Therefore the individuals in the Atlas provide insight to the genetic landscape of Ireland before significant movement of people from the 20th century onwards. An analysis of dense genotyping data from 142participants shows that the Atlas participants cluster closely with British individuals in a Europe wide PCA, but present different ancestral population components when compared with British, and other European populations. Irish individuals also present slightly higher levels of homozygosity relative to mainland European levels. PCA targeted at specific areas of interest within Ireland also hint at fine-scale substructure. Conclusion Ireland shows typical features of a homogenous population, well suited to the study of rare variation in disease risk., Background Progress in diagnostic and therapeutic strategies in medicine is dependent upon high-quality biomedical research. Translation of research findings into the clinic relies on patient participation in innovative clinical trials. We investigated attitudes to genetic research in Ireland, in particular with respect to commercial and financial implications. Methods A multi-centre cross-sectional survey study was performed. Consecutive patients attending four out-patient clinics were asked to complete paper-based questionnaires. An electronic version of the same questionnaire was created on Survey Monkey with a link made public on a social media website for a period of 24 hours. Data was analysed using SPSS. Results 351 questionnaires were completed (99 paper, 252 electronic). The majority of respondents were female (n = 288, 82%), and highly educated, with 244 (70%) attending college/university. Most participants supported genetic research (267, 76%), more frequently for common diseases (274, 78%) than rare disorders (204, 58%, p < 0.001, x2). 103 (29%) had participated in scientific research, and 57(16%) had donated material to a bio-bank. The majority (n = 213, 61%) would not support research with potential financial/commercial gain. 106(30%) would decline to participate in research if researchers would benefit financially, compared to 49(14%) if the research was supported by a pharmaceutical company, (p < 0.001, x2). Respondents would provide buccal samples (258, 74%) more readily than tissue (225, 64%) or blood (222, 63%). Conclusion A high level of support for genetic research exists among the Irish population, but active participation is dependent upon a number of factors, notably, type of biological material required, frequency of the disease in question, and commercial interest of the researchers., Introduction Although the etiology of schizophrenia (SZ) is largely unknown, it is increasingly clear that genetic and environmental interactions contribute to cognitive deficits associated with this disorder. Recent Genome wide association studies (GWAS) have indicated a link between SZ and immune dysregulation, especially genetic mutations related to the major histocompatibility complex (MHC). Cognitive deficits are core features of Schizophrenia and related disorders, which relate to genetic risk. This study aims to explore the relationship between MHC risk variants for SZ and cognitive deficits, while also relating findings to brain activity. Methods To test if MHC risk variants impair cognition, ANCOVA analysis is performed on genetics data previously collected in a GWAS. Cognition measures are compared in groups with and without MHC genetic risk, in a population of SZ sufferers and healthy controls. Functional MRI imaging will also be performed to test if genetic risk relates to altered neural activity. Results Preliminary analyses suggest that MHC risk variants contribute to impairments in cognition in domains of social cognition, IQ and attention. Further analysis will be performed to test for environmental mediators of this relationship, looking at cannabis use and urbanicity. BOLD fMRI will also be used to test for a relationship between MHC risk and altered neural activity, using MATLAB SPM. Conclusions The MHC genetic variant may serve as a significant risk marker for schizophrenia, and further elucidate etiology of this neurodevelopmental disorder. Future studies on neurobiology of social cognition, and greater knowledge of genetic risk may establish targets for interventions., Aim To create a bioluminescence mouse model which expresses firefly luciferase in the corneal epithelium to assess gene editing and gene silencing for the cornea. Methods A gene targeting vector was generated where the Krt12 coding sequence in and the splice donor site of exon 1 were replaced with a transgene cassette containing a luc2-Multiple Targeting Cassette (MTC) gene fusion. The vector was transfected by electroporation into the Taconic Artemis C57BL/6N Tac ES cell line. Homologous recombinant clones were isolated and validated, and the mice bred with luc2-positive/ PuroR-negative offspring used for colony establishment. To visualise the expression of luc2 within the corneal epithelium, luciferin substrate diluted in viscotears was applied to the front of the eye and then luciferase expression was imaged and assessed using a Xenogen IVIS Lumina Imager and LivingImage 3.2 software. Intrastromal injection of siGlo siRNA was used to determine the localisation of siRNA within the corneal epithelium and then the established mouse model was treated with either native or Accell “self-delivery” siRNA. Results The Accell “self-delivery” siRNA induced potent sustained allele specific silencing for 7 days, while native versions of siRNA resulted in significant knock-down for 1 day only (p < 0.05). We have created and validated a bioluminescence mouse model and have utilised it to assess siRNA in vivo. This mouse model coupled with the Lumina imager will allow us to assess topical delivery of gene therapies to the ocular surface allowing validation for future translation to clinical use., Background Methylation of DNA sequences at promoters, CpG islands and other elements plays a vital role in regulating gene activity. In human, loss of methylation is known to play a causative role in imprinting disorders and in inappropriate germline gene expression in cancers. While in mouse, loss of function mutants have given great insight into the targets of methylation, functional studies in human have been largely limited to cancer cells and more recently stem cells, not normal adult cells. Methods Stable knockdowns of the maintenance methyltransferase DNMT1 were generated in normosomic hTERT-immortalised adult fibroblasts. Genome-wide methylation levels were assayed using the Illumina 450K bead array. Results were analysed using RnBeads and Galaxy. Locusspecific methylation was verified using pyrosequencing and clonal analysis. Validation was achieved using transient siRNA. Results Loss of function was poorly tolerated and all clonally-expanded cell lines had spontaneously restored DNMT1 levels by silencing of the shRNA. Evidence for a genome-wide methylation erasure event followed by a wave of remethylation could be clearly traced. Gene bodies and the shores of CpG islands showed the clearest loss of methylation overall. While most CpG islands are normally unmethylated and so unaffected, both imprints and germline genes fall into the rarer category of normally methylated islands: of these two, lasting loss of methylation was much more common among imprints than germline genes. Conclusions 1: transient loss of methylation is poorly tolerated; 2: a robust mechanism for remethylation exists even in adult cells; 3: aberrant remethylation is frequent on recovery and 4: Imprints are particularly sensitive., Background Dihydrofolate reductase (DHFR) is essential for the conversion of folic acid to active folate needed for one-carbon metabolism. Common genetic variation within DHFR is restricted to the noncoding regions and previous studies have focused on a 19 bp deletion/insertion polymorphism (rs70991108) within intron 1. Reports of an association between this polymorphism and blood folate biomarker concentrations are conflicting. Objective We aimed to evaluate whether the DHFR 19bp deletion/ insertion polymorphism affects circulating folate biomarkers in the largest cohort to address this question to date. Methods Young healthy Irish individuals (n= 2,507) between 19 to 36 years old were recruited between February 2003 and 2004. Folic acid intake from supplements and fortified foods was assessed using a customized food intake questionnaire. Concentrations of serum folate and vitamin B-12, red blood cell (RBC) folate and plasma total homocysteine (tHcy) concentration were measured. Data were analysed using linear regression models. Results Folic acid intake was positively associated with serum (P 326μg folic acid/day; P = 0.96). A non-significant trend towards lower RBC folate by genotype (P = 0.09) was observed in the lowest folic acid intake quintile (0 – 51 μg/day). Conclusion In this cohort of young healthy individuals the DHFR 19bp deletion allele does not significantly affect circulating folate status, irrespective of folic acid intake. Our data rule out a strong functional effect of this polymorphism on blood folate concentrations.
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- 2015
24. Not foreign to each other: Commonwealth Prime Ministers' Conferences 1944-1969
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O'Shea, R and Darwin, J
- Abstract
The Commonwealth Prime Ministers' Conferences were a unique experiment. They were an attempt at an intermediate mode of multilateral relations: members were no longer bound in an imperial hierarchy, nor were they fully foreign. A conscious effort was made to position the Commonwealth as a family, and the Conferences as their periodic reunion. Avoiding a 'diplomatic' culture at the Conferences in favour of a familial veneer allowed participants to claim that binding resolutions were not necessary and that meaningful cooperation could occur by consensus. This appeared to offer potential for forging a 'third way' between superpower blocs in a Cold War environment. This thesis makes an important contribution to the existing Commonwealth literature as the Conferences were the core structure of the Commonwealth until the formation of the Commonwealth Secretariat in 1965, yet have never been the subject of a full-length study. The thesis also engages with the concept of the 'British world', arguing that the Conferences had a major role in projecting British 'soft power' once martial or economic hegemony proved impracticable. By drawing on archival sources in eight Commonwealth countries, this thesis shows that the Conferences were effective in facilitating discussions on flashpoint topics such as white minority rule in South Africa and Rhodesia, even if the Commonwealth failed to fulfil hopes that it would remain an important international grouping. The study also has contemporary relevance, given that the Conferences continue as Commonwealth Heads of Government Meetings, and that questions of transnational identity and 'foreignness' continue to shape debates over Britain's relationship with Europe and its 'world role'.
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- 2017
25. MUTYH-Associated Polyposis: The Irish Experience
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Terri McVeigh, Duff M, Carroll C, O'Shea R, Bradley L, Farrell M, Dj, Gallagher, Clabby C, and Aj, Green
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Phenotype ,Adenomatous Polyposis Coli ,Genotype ,Incidence ,Mutation ,Humans ,Intestinal Polyps ,Genetic Predisposition to Disease ,Colorectal Neoplasms ,Ireland ,DNA Glycosylases ,Retrospective Studies - Abstract
MUTYH is involved in DNA damage repair. Bi-allelic MUTYH mutations predispose to polyposis and gastrointestinal malignancies, distinct genetically from autosomal dominant familial adenomatous polyposis coli. Two common European MUTYH mutations account for 90% of MUTYH-associated polyposis (MAP). We aimed to examine the incidence of MAP in Ireland. A retrospective cohort study was undertaken. Patients undergoing MUTYH testing from 2003-2016 were identified by searching electronic databases using terms "MUTYH" and "MYH". Phenotypic and genotypic details were obtained by chart review. Bi-allelic mutations were confirmed in 26 individuals (17 families), of whom 16 (62%) developed colorectal malignancies, and 22(85%) polyposis. Eleven families had bi-allelic status for one/both common European mutations. Regional variation was noted, with over-representation of bi-allelic mutation carriers in the South-west of Ireland. MAP is under-diagnosed in Ireland. Increased awareness is required to facilitate appropriate identification and surveillance of bi-allelic mutation carriers for colorectal pathology.
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- 2017
26. Prevalence and architecture of de novo mutations in developmental disorders
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McRae, JF, Clayton, S, Fitzgerald, TW, Kaplanis, J, Prigmore, E, Rajan, D, Sifrim, A, Aitken, S, Akawi, N, Alvi, M, Ambridge, K, Barrett, DM, Bayzetinova, T, Jones, P, Jones, WD, King, D, Krishnappa, N, Mason, LE, Singh, T, Tivey, AR, Ahmed, M, Anjum, U, Archer, H, Armstrong, R, Awada, J, Balasubramanian, M, Banka, S, Baralle, D, Barnicoat, A, Batstone, P, Baty, D, Bennett, C, Berg, J, Bernhard, B, Bevan, AP, Bitner-Glindzicz, M, Blair, E, Blyth, M, Bohanna, D, Bourdon, L, Bourn, D, Bradley, L, Brady, A, Brent, S, Brewer, C, Brunstrom, K, Bunyan, DJ, Burn, J, Canham, N, Castle, B, Chandler, K, Chatzimichali, E, Cilliers, D, Clarke, A, Clasper, S, Clayton-Smith, J, Clowes, V, Coates, A, Cole, T, Colgiu, I, Collins, A, Collinson, MN, Connell, F, Cooper, N, Cox, H, Cresswell, L, Cross, G, Crow, Y, D’Alessandro, M, Dabir, T, Davidson, R, Davies, S, de Vries, D, Dean, J, Deshpande, C, Devlin, G, Dixit, A, Dobbie, A, Donaldson, A, Donnai, D, Donnelly, D, Donnelly, C, Douglas, A, Douzgou, S, Duncan, A, Eason, J, Ellard, S, Ellis, I, Elmslie, F, Evans, K, Everest, S, Fendick, T, Fisher, R, Flinter, F, Foulds, N, Fry, A, Fryer, A, Gardiner, C, Gaunt, L, Ghali, N, Gibbons, R, Gill, H, Goodship, J, Goudie, D, Gray, E, Green, A, Greene, P, Greenhalgh, L, Gribble, S, Harrison, R, Harrison, L, Harrison, V, Hawkins, R, He, L, Hellens, S, Henderson, A, Hewitt, S, Hildyard, L, Hobson, E, Holden, S, Holder, M, Holder, S, Hollingsworth, G, Homfray, T, Humphreys, M, Hurst, J, Hutton, B, Ingram, S, Irving, M, Islam, L, Jackson, A, Jarvis, J, Jenkins, L, Johnson, D, Jones, E, Josifova, D, Joss, S, Kaemba, B, Kazembe, S, Kelsell, R, Kerr, B, Kingston, H, Kini, U, Kinning, E, Kirby, G, Kirk, C, Kivuva, E, Kraus, A, Kumar, D, Kumar, VKA, Lachlan, K, Lam, W, Lampe, A, Langman, C, Lees, M, Lim, D, Longman, C, Lowther, G, Lynch, SA, Magee, A, Maher, E, Male, A, Mansour, S, Marks, K, Martin, K, Maye, U, McCann, E, McConnell, V, McEntagart, M, McGowan, R, McKay, K, McKee, S, McMullan, DJ, McNerlan, S, McWilliam, C, Mehta, S, Metcalfe, K, Middleton, A, Miedzybrodzka, Z, Miles, E, Mohammed, S, Montgomery, T, Moore, D, Morgan, S, Morton, J, Mugalaasi, H, Murday, V, Murphy, H, Naik, S, Nemeth, A, Nevitt, L, Newbury-Ecob, R, Norman, A, O’Shea, R, Ogilvie, C, Ong, K-R, Park, S-M, Parker, MJ, Patel, C, Paterson, J, Payne, S, Perrett, D, Phipps, J, Pilz, DT, Pollard, M, Pottinger, C, Poulton, J, Pratt, N, Prescott, K, Price, S, Pridham, A, Procter, A, Purnell, H, Quarrell, O, Ragge, N, Rahbari, R, Randall, J, Rankin, J, Raymond, L, Rice, D, Robert, L, Roberts, E, Roberts, J, Roberts, P, Roberts, G, Ross, A, Rosser, E, Saggar, A, Samant, S, Sampson, J, Sandford, R, Sarkar, A, Schweiger, S, Scott, R, Scurr, I, Selby, A, Seller, A, Sequeira, C, Shannon, N, Sharif, S, Shaw-Smith, C, Shearing, E, Shears, D, Sheridan, E, Simonic, I, Singzon, R, Skitt, Z, Smith, A, Smith, K, Smithson, S, Sneddon, L, Splitt, M, Squires, M, Stewart, F, Stewart, H, Straub, V, Suri, M, Sutton, V, Swaminathan, GJ, Sweeney, E, Tatton-Brown, K, Taylor, C, Taylor, R, Tein, M, Temple, IK, Thomson, J, Tischkowitz, M, Tomkins, S, Torokwa, A, Treacy, B, Turner, C, Turnpenny, P, Tysoe, C, Vandersteen, A, Varghese, V, Vasudevan, P, Vijayarangakannan, P, Vogt, J, Wakeling, E, Wallwark, S, Waters, J, Weber, A, Wellesley, D, Whiteford, M, Widaa, S, Wilcox, S, Wilkinson, E, Williams, D, Williams, N, Wilson, L, Woods, G, Wragg, C, Wright, M, Yates, L, Yau, M, Nellåker, C, Parker, M, Firth, HV, Wright, CF, FitzPatrick, DR, Barrett, JC, and Hurles, ME
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Male ,Parents ,Heredity ,Developmental Disabilities ,GRIN2B ,POGZ ,Autoantigens ,SMAD4 ,CASK ,GATAD2B ,0302 clinical medicine ,TRIO ,SMARCA2 ,KCNH1 ,Average Faces ,CTNNB1 ,SCN1A ,Young adult ,Casein Kinase II ,Child ,AUTS2 ,MEF2C ,Exome ,ADNP ,Exome sequencing ,EP300 ,KCNQ2 ,KCNQ3 ,EHMT1 ,CNKSR2 ,CREBBP ,MYT1L ,MED13L ,CSNK2A1 ,Protein Phosphatase 2C ,PPP2R1A ,ZBTB18 ,CDKL5 ,WAC ,HNRNPU ,Cohort ,STXBP1 ,Medical genetics ,SYNGAP1 ,Mi-2 Nucleosome Remodeling and Deacetylase Complex ,Sex characteristics ,AHDC1 ,SCN8A ,medicine.medical_specialty ,SLC6A1 ,FOXP1 ,USP9X ,Article ,ANKRD11 ,PUF60 ,BRAF ,03 medical and health sciences ,SATB2 ,SMC1A ,Intellectual Disability ,BCL11A ,GABRB3 ,IQSEC2 ,Humans ,TBL1XR1 ,TCF4 ,MSL3 ,TCF20 ,DNM1 ,EEF1A2 ,SUV420H1 ,DYRK1A ,SETD5 ,COL4A3BP ,CTCF ,CHD2 ,R1 ,CHD4 ,030104 developmental biology ,NAA10 ,HDAC8 ,Mutation ,KDM5B ,CHAMP1 ,PhenIcons ,030217 neurology & neurosurgery ,Transcription Factors ,0301 basic medicine ,ZMYND11 ,PTEN ,De novo mutation ,Chromosomal Proteins, Non-Histone ,PTPN11 ,ASXL1 ,Bioinformatics ,medicine.disease_cause ,ASXL3 ,Cohort Studies ,DEAD-box RNA Helicases ,CHD8 ,Prevalence ,QRICH1 ,KIF1A ,Genetics ,Sex Characteristics ,GNAI1 ,Multidisciplinary ,WDR45 ,Middle Aged ,KMT2A ,PPM1D ,MECP2 ,DNA-Binding Proteins ,PPP2R5D ,Phenotype ,PACS1 ,ras GTPase-Activating Proteins ,DDX3X ,Female ,FOXG1 ,SET ,Myeloid-Lymphoid Leukemia Protein ,Developmental Disease ,Adult ,KANSL1 ,Adolescent ,NFIX ,Nerve Tissue Proteins ,PURA ,Biology ,KAT6B ,KAT6A ,NSD1 ,PDHA1 ,ALG13 ,Young Adult ,Seizures ,CDC2 Protein Kinase ,medicine ,Journal Article ,QH426 ,Homeodomain Proteins ,ITPR1 ,DYNC1H1 ,GNAO1 ,Histone-Lysine N-Methyltransferase ,Sequence Analysis, DNA ,ZC4H2 ,ARID1B ,Repressor Proteins ,CNOT3 ,SCN2A ,SLC35A2 ,CDK13 - Abstract
Children with severe, undiagnosed developmental disorders (DDs) are enriched for damaging de novo mutations (DNMs) in developmentally important genes. We exome sequenced 4,294 families with children with DDs, and meta-analysed these data with published data on 3,287 children with similar disorders. We show that the most significant factors influencing the diagnostic yield of de novo mutations are the sex of the child, the relatedness of their parents and the age of both father and mother. We identified 95 genes enriched for damaging de novo mutation at genome-wide significance (P < 5 x 10-7), including fourteen genes for which compelling data for causation was previously lacking. The large number of genome-wide significant findings allow us to demonstrate that, at current cost differentials, exome sequencing has much greater power than genome sequencing for novel gene discovery in genetically heterogeneous disorders. We estimate that 42.5% of our cohort likely carry pathogenic de novo single nucleotide variants (SNVs) and indels in coding sequences, with approximately half operating by a loss-of-function mechanism, and the remainder being gain-of-function. We established that most haploinsufficient developmental disorders have already been identified, but that many gain-of-function disorders remain to be discovered. Extrapolating from the DDD cohort to the general population, we estimate that de novo dominant developmental disorders have an average birth prevalence of 1 in 168 to 1 in 377, depending on parental age.
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- 2017
27. Techno-Economic Optimisation of Combined Anaerobic Digestion and Gasification of Food Waste as Part of an Integrated Waste Management and Energy System
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Singlitico, A., Dussan, K., O’shea, R., David Wall, Goggins, J., Murphy, J., and Monaghan, R. F. D.
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Biomass - Abstract
Ireland produces 642,000 t of separated household organic waste or “food waste” annually. In 2016, only 420,000 t of biodegradable waste was permitted to landfill following the EU Directive 1999/31/EC. Growing population and restrictive directives are making landfills unfeasible. Anaerobic digestion (AD) offers an initial waste management measure of food waste (organic fraction of municipal solid waste). Gasification is an attractive process that can extract the remaining energy in the waste and reduce the final volume. This work explores the use of a food waste treatment network in Ireland in which AD and gasification are integrated with cogeneration of heat and electricity in a waste-to-energy national scheme. This work includes a parametric optimisation of AD and gasification of food waste based on experimental data and process modelling. A Geographic Information System algorithm locates and designs facilities for waste treatment, distribution and conversion to energy that minimise the energy involved in transporting food waste to treatment facilities. A techno-economic evaluation of the system is performed that minimises the levelised cost of power generation and maximises the energy output. This work presents the benefits of this waste-to-energy network and provides a sustainable alternative to current waste management practices in Ireland and other regions where landfills and other methods are environmentally harmful., Proceedings of the 25th European Biomass Conference and Exhibition, 12-15 June 2017, Stockholm, Sweden, pp. 96-105
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- 2017
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28. Large-scale discovery of novel genetic causes of developmental disorders
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Fitzgerald, T.W., Gerety, S.S., Jones, W.D., van Kogelenberg, M., King, D.A., McRae, J., Morley, K.I., Parthiban, V., Al-Turki, S., Ambridge, K., Barrett, D.M., Bayzetinova, T., Clayton, S., Coomber, E.L., Gribble, S., Jones, P., Krishnappa, N., Mason, L.E., Middleton, A., Miller, R., Prigmore, E., Rajan, D., Sifrim, A., Tivey, A.R., Ahmed, M., Akawi, N., Andrews, R., Anjum, U., Archer, H., Armstrong, R., Balasubramanian, M., Banerjee, R., Baralle, D., Batstone, P., Baty, D., Bennett, C., Berg, J., Bernhard, B., Bevan, A.P., Blair, E., Blyth, M., Bohanna, D., Bourdon, L., Bourn, D., Brady, A., Bragin, E., Brewer, C., Brueton, L., Brunstrom, K., Bumpstead, S.J., Bunyan, D.J., Burn, J., Burton, J., Canham, N., Castle, B., Chandler, K., Clasper, S., Clayton-Smith, J., Cole, T., Collins, A., Collinson, M.N., Connell, F., Cooper, N., Cox, H., Cresswell, L., Cross, G., Crow, Y., D'Alessandro, M., Dabir, T., Davidson, R., Davies, S., Dean, J., Deshpande, C., Devlin, G., Dixit, A., Dominiczak, A., Donnelly, C., Donnelly, D., Douglas, A., Duncan, A., Eason, J., Edkins, S., Ellard, S., Ellis, P., Elmslie, F., Evans, K., Everest, S., Fendick, T., Fisher, R., Flinter, F., Foulds, N., Fryer, A., Fu, B., Gardiner, C., Gaunt, L., Ghali, N., Gibbons, R., Pereira, S.L.G., Goodship, J., Goudie, D., Gray, E., Greene, P., Greenhalgh, L., Harrison, L., Hawkins, R., Hellens, S., Henderson, A., Hobson, E., Holden, S., Holder, S., Hollingsworth, G., Homfray, T., Humphreys, M., Hurst, J., Ingram, S., Irving, M., Jarvis, J., Jenkins, L., Johnson, D., Jones, D., Jones, E., Josifova, D., Joss, S., Kaemba, B., Kazembe, S., Kerr, B., Kini, U., Kinning, E., Kirby, G., Kirk, C., Kivuva, E., Kraus, A., Kumar, D., Lachlan, K., Lam, W., Lampe, A., Langman, C., Lees, M., Lim, D., Lowther, G., Lynch, S.A., Magee, A., Maher, E., Mansour, S., Marks, K., Martin, K., Maye, U., McCann, E., McConnell, V., McEntagart, M., McGowan, R., McKay, K., McKee, S., McMullan, D.J., McNerlan, S., Mehta, S., Metcalfe, K., Miles, E., Mohammed, S., Montgomery, T., Moore, D., Morgan, S., Morris, A., Morton, J., Mugalaasi, H., Murday, V., Nevitt, L., Newbury-Ecob, R., Norman, A., O'Shea, R., Ogilvie, C., Park, S., Parker, M.J., Patel, C., Paterson, J., Payne, S., Phipps, J., Pilz, D.T., Porteous, D., Pratt, N., Prescott, K., Price, S., Pridham, A., Procter, A., Purnell, H., Ragge, N., Rankin, J., Raymond, L., Rice, D., Robert, L., Roberts, E., Roberts, G., Roberts, J., Roberts, P., Ross, A., Rosser, E., Saggar, A., Samant, S., Sandford, R., Sarkar, A., Schweier, S., Scott, C., Scott, R., Selby, A., Seller, A., Sequeira, C., Shannon, N., Shanrif, S., Shaw-Smith, C., Shearing, E., Shears, D., Simonic, I., Simpkin, D., Singzon, R., Skitt, Z., Smith, A., Smith, B., Smith, K., Smithson, S., Sneddon, L., Splitt, M., Squires, M., Stewart, F., Stewart, H., Suri, M., Sutton, V., Swaminathan, G.J., Sweeney, E., Tatton-Brown, K., Taylor, C., Taylor, R., Tein, M., Temple, I.K., Thomson, J., Tolmie, J., Torokwa, A., Treacy, B., Turner, C., Turnpenny, P., Tysoe, C., Vandersteen, A., Vasudevan, P., Vogt, J., Wakeling, E., Walker, D., Waters, J., Weber, A., Wellesley, D., Whiteford, M., Widaa, S., Wilcox, S., Williams, D., Williams, N., Woods, G., Wragg, C., Wright, M., Yang, F., Yau, M., Carter, N.P., Parker, M., Firth, H.V., FitzPatrick, D.R., Wright, C.F., Barrett, J.C., Hurles, M.E., and The Deciphering Developmental Disorders Study, .
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Male ,Parents ,Chromosomal Proteins, Non-Histone ,Developmental Disabilities ,Transposases ,SYNGAP1 ,medicine.disease_cause ,Bioinformatics ,DEAD-box RNA Helicases ,0302 clinical medicine ,Guanine Nucleotide Exchange Factors ,Missense mutation ,Exome ,Protein Phosphatase 2 ,Child ,Dynamin I ,Zebrafish ,Exome sequencing ,Genes, Dominant ,Polycomb Repressive Complex 1 ,0303 health sciences ,Mutation ,Multidisciplinary ,Gene Expression Regulation, Developmental ,Nuclear Proteins ,DNA-Binding Proteins ,Child, Preschool ,Female ,Adolescent ,Mutation, Missense ,Nerve Tissue Proteins ,Protein Serine-Threonine Kinases ,Biology ,Article ,03 medical and health sciences ,Rare Diseases ,medicine ,Animals ,Humans ,030304 developmental biology ,Chromosome Aberrations ,Homeodomain Proteins ,Genome, Human ,Mechanism (biology) ,Infant, Newborn ,Infant ,Phosphoproteins ,United Kingdom ,Human genetics ,Repressor Proteins ,Human genome ,Carrier Proteins ,030217 neurology & neurosurgery ,Transcription Factors - Abstract
Despite three decades of successful, predominantly phenotype-driven discovery of the genetic causes of monogenic disorders1, up to half of children with severe developmental disorders of probable genetic origin remain without a genetic diagnosis. Particularly challenging are those disorders rare enough to have eluded recognition as a discrete clinical entity, those with highly variable clinical manifestations, and those that are difficult to distinguish from other, very similar, disorders. Here we demonstrate the power of using an unbiased genotype-driven approach2 to identify subsets of patients with similar disorders. By studying 1,133 children with severe, undiagnosed developmental disorders, and their parents, using a combination of exome sequencing3,4,5,6,7,8,9,10,11 and array-based detection of chromosomal rearrangements, we discovered 12 novel genes associated with developmental disorders. These newly implicated genes increase by 10% (from 28% to 31%) the proportion of children that could be diagnosed. Clustering of missense mutations in six of these newly implicated genes suggests that normal development is being perturbed by an activating or dominant-negative mechanism. Our findings demonstrate the value of adopting a comprehensive strategy, both genome-wide and nationwide, to elucidate the underlying causes of rare genetic disorders.
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- 2015
29. Radiologically inserted gastrostomy tubes in head and neck cancer patients – demographics, treatment modality and complication rates – our experience over three years in 101 consecutive cases
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Tuckett, J., primary, O'Shea, R., additional, Hevers, A., additional, Perrot, L., additional, Byrne, H., additional, Murphy, M., additional, and Sheahan, P., additional
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- 2015
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30. Impact of current smoking and alcohol on gastrostomy duration in patients with head and neck cancer undergoing definitive chemoradiotherapy
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Tuckett, J., primary, O'Shea, R., additional, Byrne, H., additional, Taylor, E., additional, O’Leary, G., additional, and Sheahan, P., additional
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- 2015
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31. DVD Versus Physiotherapist-Led Inhaler Education: A Randomised Controlled Trial.
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Khan, R., Yasin, F., O'Neill, S., Cahalane, E., O'Shea, R., Browne, B., Cournane, J., Rand, S., and Shannon, H.
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- 2018
32. Next generation sequencing is informing phenotype: a TP53 example.
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O’Shea, R., Clarke, R., Berkley, E., Giffney, C., Farrell, M., O’Donovan, E., and Gallagher, D. J.
- Abstract
The increased availability of next generation sequencing (NGS) and multi gene panel testing has resulted in more frequent TP53 testing of families that do not meet classic testing criteria. We investigated testing criteria, family history and result outcome in a cohort of Irish probands undergoing TP53 full sequencing. All TP53 test requests processed through the national genetic testing laboratory between 2012 and 2014 were retrospectively reviewed. Personal and family cancer histories were collected, including tumour type and age at diagnosis, from two adult cancer genetic services in Ireland. Association between Li Fraumeni syndrome (LFS) or Li Fraumeni like syndrome (LFL) criteria and test result was examined. One hundred and 35 TP53 test requests were identified. Family history data and test results were available on 123 of the TP53 test requests (118 female; 5 male). 59/123 (48%) did not meet classic LFS or LFL criteria. Two individuals from this group harboured pathogenic TP53 mutations, giving a 3% mutation detection rate in those not meeting testing criteria. Both were female and had a personal history of early onset bilateral breast cancer with no reported LFS cancers in the family. 64/123 (52%) met LFS or LFL criteria and were all TP53 negative. 37/64 (57.8%) met Chompret criteria, 19/64 (29.7%) met Eeles and 7/64 (10.9%) met Eeles and Chompret and 1/64 (1.6%) met Classic LFS criteria. Stringent testing criteria miss germline mutations in TP53. Broadening the criteria for TP53 testing may improve our understanding of the phenotype and penetrance in the association syndrome. [ABSTRACT FROM AUTHOR]
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- 2018
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33. P0144 : Two testing strategies for covert hepatic encephalopathy diagnosis stabilizes agreement between sites in a multi-center analysis: validation of the EASL/AASLD he guidelines
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Allampati, S., primary, Duarte-Rojo, A., additional, Thacker, L., additional, White, M., additional, Unser, A., additional, Gavis, E., additional, Hovermale, J., additional, Heuman, D.M., additional, John, B., additional, Klair, J.S., additional, Flud, C., additional, O'Shea, R., additional, and Bajaj, J.S., additional
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- 2015
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34. P.2.f.015 Biomarkers of the rapid clinical response to ketamine in treatment-resistant depression: focus on kynurenine
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Clarke, G., primary, Naughton, M., additional, O'Shea, R., additional, Dowling, J., additional, Walsh, A., additional, Ismail, F., additional, Shorten, G., additional, Scott, L., additional, Cryan, J.F., additional, and Dinan, T.G., additional
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- 2014
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35. Predicting programmed death-ligand 1 (PD-L1) expression with fluorine-18 fluorodeoxyglucose ([ 18 F]FDG) positron emission tomography/computed tomography (PET/CT) metabolic parameters in resectable non-small cell lung cancer.
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Hughes DJ, Josephides E, O'Shea R, Manickavasagar T, Horst C, Hunter S, Tanière P, Nonaka D, Van Hemelrijck M, Spicer J, Goh V, Bille A, Karapanagiotou E, and Cook GJR
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- Humans, Male, Female, Aged, Middle Aged, Retrospective Studies, Aged, 80 and over, Adult, Lymphatic Metastasis diagnostic imaging, Carcinoma, Non-Small-Cell Lung diagnostic imaging, Carcinoma, Non-Small-Cell Lung metabolism, Carcinoma, Non-Small-Cell Lung surgery, Fluorodeoxyglucose F18, Positron Emission Tomography Computed Tomography methods, Lung Neoplasms diagnostic imaging, Lung Neoplasms metabolism, B7-H1 Antigen metabolism, Radiopharmaceuticals
- Abstract
Background: Programmed death-ligand 1 (PD-L1) expression is a predictive biomarker for immunotherapy in non-small cell lung cancer (NSCLC). PD-L1 and glucose transporter 1 expression are closely associated, and studies demonstrate correlation of PD-L1 with glucose metabolism., Aim: The aim of this study was to investigate the association of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([
18 F]FDG-PET/CT) metabolic parameters with PD-L1 expression in primary lung tumour and lymph node metastases in resected NSCLC., Methods: We conducted a retrospective analysis of 210 patients with node-positive resectable stage IIB-IIIB NSCLC. PD-L1 tumour proportion score (TPS) was determined using the DAKO 22C3 immunohistochemical assay. Semi-automated techniques were used to analyse pre-operative [18 F]FDG-PET/CT images to determine primary and nodal metabolic parameter scores (including max, mean, peak and peak adjusted for lean body mass standardised uptake values (SUV), metabolic tumour volume (MTV), total lesional glycolysis (TLG) and SUV heterogeneity index (HISUV))., Results: Patients were predominantly male (57%), median age 70 years with non-squamous NSCLC (68%). A majority had negative primary tumour PD-L1 (TPS < 1%; 53%). Mean SUVmax , SUVmean , SUVpeak and SULpeak values were significantly higher (p < 0.05) in those with TPS ≥ 1% in primary tumour (n = 210) or lymph nodes (n = 91). However, ROC analysis demonstrated only moderate separability at the 1% PD-L1 TPS threshold (AUCs 0.58-0.73). There was no association of MTV, TLG and HISUV with PD-L1 TPS., Conclusion: This study demonstrated the association of SUV-based [18 F]FDG-PET/CT metabolic parameters with PD-L1 expression in primary tumour or lymph node metastasis in resectable NSCLC, but with poor sensitivity and specificity for predicting PD-L1 positivity ≥ 1%., Clinical Relevance Statement: Whilst SUV-based fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography metabolic parameters may not predict programmed death-ligand 1 positivity ≥ 1% in the primary tumour and lymph nodes of resectable non-small cell lung cancer independently, there is a clear association which warrants further investigation in prospective studies., Trial Registration: Non-applicable KEY POINTS: • Programmed death-ligand 1 immunohistochemistry has a predictive role in non-small cell lung cancer immunotherapy; however, it is both heterogenous and dynamic. • SUV-based fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18 F]FDG-PET/CT) metabolic parameters were significantly higher in primary tumour or lymph node metastases with positive programmed death-ligand 1 expression. • These SUV-based parameters could potentially play an additive role along with other multi-modal biomarkers in selecting patients within a predictive nomogram., (© 2024. The Author(s).)- Published
- 2024
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36. Genomic Testing in Patients with Kidney Failure of an Unknown Cause: A National Australian Study.
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Mallawaarachchi AC, Fowles L, Wardrop L, Wood A, O'Shea R, Biros E, Harris T, Alexander SI, Bodek S, Boudville N, Burke J, Burnett L, Casauria S, Chadban S, Chakera A, Crafter S, Dai P, De Fazio P, Faull R, Honda A, Huntley V, Jahan S, Jayasinghe K, Jose M, Leaver A, MacShane M, Madelli EO, Nicholls K, Pawlowski R, Rangan G, Snelling P, Soraru J, Sundaram M, Tchan M, Valente G, Wallis M, Wedd L, Welland M, Whitlam J, Wilkins EJ, McCarthy H, Simons C, Quinlan C, Patel C, Stark Z, and Mallett AJ
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- Humans, Australia, Male, Female, Middle Aged, Aged, Adult, Genetic Testing, Renal Insufficiency genetics, Renal Insufficiency diagnosis
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- 2024
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37. Implementation and Evaluation of a National Multidisciplinary Kidney Genetics Clinic Network Over 10 Years.
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Jayasinghe K, Biros E, Harris T, Wood A, O'Shea R, Hill L, Fowles L, Wardrop L, Shalhoub C, Hahn D, Rangan G, Kevin L, Tchan M, Snelling P, Sandow R, Sundaram M, Chaturvedi S, Trnka P, Faull R, Poplawski NK, Huntley V, Garza D, Wallis M, Jose M, Leaver A, Trainer AH, Wilkins EJ, White S, Elbaum Y, Prawer Y, Krzesinski E, Valente G, Winship I, Ryan J, Whitlam J, Nicholls K, West K, Donaldson L, Johnstone L, Lewit-Mendes M, Kerr PG, Bodek S, Chakera A, MacShane M, Mincham C, Stackpoole E, Willis F, Soraru J, Pachter N, Bennetts B, Forbes TA, Mallawaarachchi A, Quinlan C, Patel C, McCarthy H, Goranitis I, Best S, Alexander S, Stark Z, and Mallett AJ
- Abstract
Introduction: Diagnostic genomic sequencing is the emerging standard of care in nephrology. There is a growing need to scale up the implementation of genomic diagnostics nationally to improve patient outcomes., Methods: This pragmatic study provided genomic or genetic testing to patients with suspected monogenic kidney disease through a national network of kidney genetics clinics (KGCs). We sought to evaluate the experiences of implementing genomic diagnostics across Australia and associated diagnostic outcomes between 2013 and 2022., Results: We successfully established and expanded a nationwide network of 20 clinics as of 2022; concurrently developing laboratory, research, and education programs to scale the clinical application of genomics in nephrology. We report on an Australian cohort of 1506 kidney patients, of whom 1322 received their test results. We assessed barriers to implementation in the nephrology context, and where possible, applied real-time solutions to improve clinical processes over 10 years., Conclusion: Developing a multidisciplinary kidney genetics model across multiple health services nationally was highly successful. This model supported optimal care of individuals with monogenic kidney disease in an economically responsible way. It has continued to evolve with technological and service developments and is now set to scale further as genomic testing for kidney patients transitions to health care system funding., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)
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- 2024
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38. Managing offshore multi-use settings: Use of conceptual mapping to reduce uncertainty of co-locating seaweed aquaculture and wind farms.
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O'Shea R, Capuzzo E, Hemming V, Grebe G, Stafford R, van den Burg SWK, Wood D, Watson G, Wells V, Johnson T, Erbs S, W van Hal J, Binnerts B, Collins AM, and Howe C
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- Uncertainty, Conservation of Natural Resources methods, Ecosystem, Seaweed, Aquaculture, Wind
- Abstract
The offshore Multi-use Setting (MUS) is a concept that aims to co-locate marine industrial activities, including wind farms and aquaculture. MUS is considered an innovative approach to promoting efficiency in space and resource use whilst contributing global policy priorities. However, the impacts of MUS development across social, economic, and environmental domains are uncertain, hindering the commercialisation of the concept. In this study, we initially demonstrate the potential consequences of co-locating seaweed aquaculture and a wind farm as a step towards MUS. Using a hypothetical case study and modified Delphi methodology, 14 subject matter experts predicted potential outcomes across social and environmental objectives. Five Cognitive maps and impact tables of 58 potential consequences were generated based on experts' perspective on co-locating seaweed aquaculture and a wind farm. The findings highlight the potential to exasperate pressures in the area, including those already attributed to wind farm operations, such as species mortality and stakeholder conflict. However, it may also enhance social-ecological conditions, such as resource provisioning and promoting habitat functionality in the region, through the addition of seaweed aquaculture. The cognitive maps demonstrate the complexity of managing MUS implementation, where high degree of variability and uncertainty about the outcomes is present. The findings of this study provide the vital entry point to performing further integrative assessment and modelling approaches, such as probabilistic analysis and simulations, in support of MUS decision-making. The research also strongly recommends alternative strategies in the pursuit of combining seaweed production and wind farms to avoid significant financial (among many other) trade-offs and risks. More broadly, we have found that our approach's ability to visually represent a complex situation while considering multiple objectives could be immensely valuable for other bioeconomy innovations or nature-based solutions. It helps mitigate the potential for expensive investments without a comprehensive evaluation of the associated risks and negative impacts, as necessitated by the principles of sustainability in decision-making., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)
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- 2024
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39. What is the power of a genomic multidisciplinary team approach? A systematic review of implementation and sustainability.
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Ma A, O'Shea R, Wedd L, Wong C, Jamieson RV, and Rankin N
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- Humans, Precision Medicine methods, Patient Care Team organization & administration, Genomics methods
- Abstract
Due to the increasing complexity of genomic data interpretation, and need for close collaboration with clinical, laboratory, and research expertise, genomics often requires a multidisciplinary team (MDT) approach. This systematic review aims to establish the evidence for effectiveness of the genomic multidisciplinary team, and the implementation components of this model that can inform precision care. MEDLINE, Embase and PsycINFO databases were searched in 2022 and 2023. We included qualitative and quantitative studies of the genomic MDT, including observational and cohort studies, for diagnosis and management, and implementation outcomes of effectiveness, adoption, efficiency, safety, and acceptability. A narrative synthesis was mapped against the Genomic Medicine Integrative Research framework. 1530 studies were screened, and 17 papers met selection criteria. All studies pointed towards the effectiveness of the genomic MDT approach, with 10-78% diagnostic yield depending on clinical context, and an increased yield of 6-25% attributed to the MDT. The genomic MDT was found to be highly efficient in interpretation of variants of uncertain significance, timeliness for a rapid result, made a significant impact on management, and was acceptable for adoption by a wide variety of subspecialists. Only one study utilized an implementation science based approach. The genomic MDT approach appears to be highly effective and efficient, facilitating higher diagnostic rates and improved patient management. However, key gaps remain in health systems readiness for this collaborative model, and there is a lack of implementation science based research especially addressing the cost, sustainability, scale up, and equity of access., (© 2024. The Author(s).)
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- 2024
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40. "We are not a typical family anymore": Exploring the experiences and support needs of fathers of children with Fragile X syndrome in Australia.
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Luermans J, Fleming J, O'Shea R, Barlow-Stewart K, Palmer EE, and Leffler M
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- Child, Male, Humans, Australia epidemiology, Family, Mental Health, Fragile X Syndrome diagnosis, Fragile X Syndrome epidemiology, Fragile X Syndrome genetics, Disabled Persons
- Abstract
A diagnosis of the X-linked condition Fragile X syndrome (FXS) in a child commonly reveals the mother's carrier status. Previous research focused on the genetic counseling process for the child and maternal family, despite calls for more research on the support needs of fathers. This study explored experiences and support needs of fathers at least 1 year after their child's FXS diagnosis to understand barriers and enablers and optimize health outcomes for the family. In-depth interviews were conducted with 11 fathers recruited through the Australian Genetics of Learning Disability Service and the Fragile X Association. Deidentified transcripts were analyzed using thematic analysis guided by an inductive approach. Four themes emerged: (1) making life easier through understanding-yesterday and today, (2) the path to a new normal-today and tomorrow, (3) seeking information and support, and (4) what men want. Fathers reported diagnostic odysseys, postdiagnostic grief, and challenges adjusting. They highlighted difficulties in understanding their child's unique behaviors and needs, responding to their partner's psychological support needs, planning for their child's future, and navigating complex health and disability systems. Participants suggested health professionals facilitate father-to-father support and psychological counseling. These findings highlight the unmet needs of fathers and suggest that a strengths-based approach is critically important given the recognized mental health impact., (© 2023 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)
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- 2024
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41. Genomic multidisciplinary teams: A model for navigating genetic mainstreaming and precision medicine.
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Ma A, Newing TP, O'Shea R, Gokoolparsadh A, Murdoch E, Hayward J, Shannon G, Kevin L, Bennetts B, Ho G, Smith J, Shah M, Jones KJ, Josephi-Taylor S, Sandaradura SA, Adès L, Jamieson R, and Rankin NM
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- Humans, Australia, Child, New South Wales, Precision Medicine methods, Patient Care Team, Genomics, Genetic Testing
- Abstract
Aim: Recent rapid advances in genomics are revolutionising patient diagnosis and management of genetic conditions. However, this has led to many challenges in service provision, education and upskilling requirements for non-genetics health-care professionals and remuneration for genomic testing. In Australia, Medicare funding with a Paediatric genomic testing item for patients with intellectual disability or syndromic features has attempted to address this latter issue. The Sydney Children's Hospitals Network - Westmead (SCHN-W) Clinical Genetics Department established Paediatric and Neurology genomic multidisciplinary team (MDT) meetings to address the Medicare-specified requirement for discussion with clinical genetics, and increasing genomic testing advice requests., Methods: This SCHN-W genomic MDT was evaluated with two implementation science frameworks - the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) and GMIR - Genomic Medicine Integrative Research frameworks. Data from June 2020 to July 2022 were synthesised and evaluated, as well as process mapping of the MDT service., Results: A total of 205 patients were discussed in 34 MDT meetings, facilitating 148 genomic tests, of which 73 were Medicare eligible. This was equivalent to 26% of SCHN-W genetics outpatient activity, and 13% of all Medicare-funded paediatric genomic testing in NSW. 39% of patients received a genetic diagnosis., Conclusion: The genomic MDT facilitated increased genomic testing at a tertiary paediatric centre and is an effective model for mainstreaming and facilitating precision medicine. However, significant implementation issues were identified including cost and sustainability, as well as the high level of resourcing that will be required to scale up this approach to other areas of medicine., (© 2024 The Authors. Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)
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- 2024
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42. A perspective on three sustainable hydrogen production technologies with a focus on technology readiness level, cost of production and life cycle environmental impacts.
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Li Y, Lin R, O'Shea R, Thaore V, Wall D, and Murphy JD
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Hydrogen will play an indispensable role as both an energy vector and as a molecule in essential products in the transition to climate neutrality. However, the optimal sustainable hydrogen production system is not definitive due to challenges in energy conversion efficiency, economic cost, and associated marginal abatement cost. This review summarises and contrasts different sustainable hydrogen production technologies including for their development, potential for improvement, barriers to large-scale industrial application, capital and operating cost, and life-cycle environmental impact. Polymer electrolyte membrane water electrolysis technology shows significant potential for large-scale application in the near-term, with a higher technology readiness level (expected to be 9 by 2030) and a levelized cost of hydrogen expected to be 4.15-6 €/kg H
2 in 2030; this equates to a 50% decrease as compared to 2020. The four-step copper-chlorine (Cu-Cl) water thermochemical cycle can perform better in terms of life cycle environmental impact than the three- and five-step Cu-Cl cycle, however, due to system complexity and high capital expenditure, the thermochemical cycle is more suitable for long-term application should the technology develop. Biological conversion technologies (such as photo/dark fermentation) are at a lower technology readiness level, and the system efficiency of some of these pathways such as biophotolysis is low (less than 10%). Biomass gasification may be a more mature technology than some biological conversion pathways owing to its higher system efficiency (40%-50%). Biological conversion systems also have higher costs and as such require significant development to be comparable to hydrogen produced via electrolysis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)- Published
- 2024
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43. Multicentre pilot randomised control trial of a self-directed exergaming intervention for poststroke upper limb rehabilitation: research protocol.
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Broderick M, Burridge J, Demain S, Johnson L, Brereton J, O'Shea R, and Bentley P
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- Humans, Exergaming, Pilot Projects, Upper Extremity, Randomized Controlled Trials as Topic, Multicenter Studies as Topic, Stroke Rehabilitation methods, Stroke complications
- Abstract
Introduction: Technology-facilitated, self-directed upper limb (UL) rehabilitation, as an adjunct to conventional care, could enhance poststroke UL recovery compared with conventional care alone, without imposing additional resource burden. The proposed pilot randomised controlled trial (RCT) aims to assess whether stroke survivors will engage in self-directed UL training, explore factors associated with intervention adherence and evaluate the study design for an RCT testing the efficacy of a self-directed exer-gaming intervention for UL recovery after stroke., Methods and Analysis: This is a multicentre, internal pilot RCT; parallel design, with nested qualitative methods. The sample will consist of stroke survivors with UL paresis, presenting within the previous 30 days. Participants randomised to the intervention group will be trained to use an exergaming device and will be supported to adopt this as part of their self-directed rehabilitation (ie, without formal support/supervision) for a 3-month period. The primary outcome will be the Fugl Meyer Upper Extremity Assessment (FM-UE) at 6 months poststroke. Secondary outcomes are the Action Research Arm Test (ARAT), the Barthel Index and the Modified Rankin Scale. Assessment time points will be prior to randomisation (0-1 month poststroke), 3 months and 6 months poststroke. A power calculation to inform sample size required for a definitive RCT will be conducted using FM-UE data from the sample across 0-6 months time points. Semistructured qualitative interviews will examine factors associated with intervention adoption. Reflexive thematic analysis will be used to code qualitative interview data and generate key themes associated with intervention adoption., Ethics and Dissemination: The study protocol (V.1.9) was granted ethical approval by the Health Research Authority, Health and Care Research Wales, and the London- Harrow Research Ethics Committee (ref. 21/LO/0054) on 19 May 2021. Trial results will be submitted for publication in peer-reviewed journals, presented at national and international stroke meetings and conferences and disseminated among stakeholder communities., Trial Registration Number: NCT04475692., Competing Interests: Competing interests: PB was involved in the Imperial College London research group who developed and conducted initial testing of the technology (GripAble) used in this study. Grip Able has since spun-out of Imperial College to form a limited company, PB does not hold a paid role within GripAble., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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44. Weakly supervised segmentation models as explainable radiological classifiers for lung tumour detection on CT images.
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O'Shea R, Manickavasagar T, Horst C, Hughes D, Cusack J, Tsoka S, Cook G, and Goh V
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Purpose: Interpretability is essential for reliable convolutional neural network (CNN) image classifiers in radiological applications. We describe a weakly supervised segmentation model that learns to delineate the target object, trained with only image-level labels ("image contains object" or "image does not contain object"), presenting a different approach towards explainable object detectors for radiological imaging tasks., Methods: A weakly supervised Unet architecture (WSUnet) was trained to learn lung tumour segmentation from image-level labelled data. WSUnet generates voxel probability maps with a Unet and then constructs an image-level prediction by global max-pooling, thereby facilitating image-level training. WSUnet's voxel-level predictions were compared to traditional model interpretation techniques (class activation mapping, integrated gradients and occlusion sensitivity) in CT data from three institutions (training/validation: n = 412; testing: n = 142). Methods were compared using voxel-level discrimination metrics and clinical value was assessed with a clinician preference survey on data from external institutions., Results: Despite the absence of voxel-level labels in training, WSUnet's voxel-level predictions localised tumours precisely in both validation (precision: 0.77, 95% CI: [0.76-0.80]; dice: 0.43, 95% CI: [0.39-0.46]), and external testing (precision: 0.78, 95% CI: [0.76-0.81]; dice: 0.33, 95% CI: [0.32-0.35]). WSUnet's voxel-level discrimination outperformed the best comparator in validation (area under precision recall curve (AUPR): 0.55, 95% CI: [0.49-0.56] vs. 0.23, 95% CI: [0.21-0.25]) and testing (AUPR: 0.40, 95% CI: [0.38-0.41] vs. 0.36, 95% CI: [0.34-0.37]). Clinicians preferred WSUnet predictions in most instances (clinician preference rate: 0.72 95% CI: [0.68-0.77])., Conclusion: Weakly supervised segmentation is a viable approach by which explainable object detection models may be developed for medical imaging., Critical Relevance Statement: WSUnet learns to segment images at voxel level, training only with image-level labels. A Unet backbone first generates a voxel-level probability map and then extracts the maximum voxel prediction as the image-level prediction. Thus, training uses only image-level annotations, reducing human workload. WSUnet's voxel-level predictions provide a causally verifiable explanation for its image-level prediction, improving interpretability., Key Points: • Explainability and interpretability are essential for reliable medical image classifiers. • This study applies weakly supervised segmentation to generate explainable image classifiers. • The weakly supervised Unet inherently explains its image-level predictions at voxel level., (© 2023. The Author(s).)
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- 2023
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45. Demand-driven biogas production from Upflow Anaerobic Sludge Blanket (UASB) reactors to balance the power grid.
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Shinde R, Hackula A, O'Shea R, Barth S, Murphy JD, and Wall DM
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- Anaerobiosis, Biofuels, Kinetics, Bioreactors, Methane, Sewage, Waste Disposal, Fluid
- Abstract
Future energy systems necessitate dispatchable renewable energy to balance electrical grids with high shares of intermittent renewables. Biogas from anaerobic digestion (AD) can generate electricity on-demand. High-rate methanogenic reactors, such as the Upflow Anaerobic Sludge Blanket (UASB), can react quicker to variations in feeding as compared to traditional AD systems. In this study, experimental trials validated the feasibility of operating the UASB in a demand-driven manner. The UASB was operated with leachate produced from a hydrolysis reactor treating grass silage. The UASB demonstrated a high degree of flexibility in responding to variable feeding regimes. The intra-day biogas production rate could be increased by up to 123% under 4 hours in demand-driven operation, without significant deterioration in performance. A model based on kinetic analysis was developed to help align demand-driven operation with the grid. The findings suggest significant opportunities for UASBs to provide positive and negative balance to the power grid., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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46. Two-phase anaerobic digestion for enhanced valorisation of whiskey distillery by-products.
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Hackula A, Shinde R, Hickey D, O'Shea R, Murphy JD, and Wall DM
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- Anaerobiosis, Alcohols, Methane, Biofuels, Bioreactors, Alcoholic Beverages
- Abstract
The valorisation of whiskey by-products was assessed and compared in three anaerobic digestion systems. The systems produced similar methane yields, which could satisfy up to 44% of the thermal energy demand at a distillery. Using methane generated from by-products would displace natural gas and reduce the distillery's carbon footprint. Two-phase systems had higher methane content (ca. 75 %vol) than the traditional system (54 %vol) and furthermore, unlocked opportunities for volatile fatty acid production. The potential value that could be generated from the extraction of butyric acid and caproic acid was approximately €6.76 million for a 50 million litre alcohol facility (0.14 € per litre of whiskey). All three anaerobic digestion systems showed the potential to valorise whiskey by-products and convert current linear distillery production processes into circular repurpose and reuse production processes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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47. A perspective on methodologies and system boundaries to develop abatement cost for on-farm anaerobic digestion.
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Diaz Huerta J, O'Shea R, Murphy J, and Wall DM
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- Animals, Cattle, Farms, Anaerobiosis, Commerce, Agriculture, Biofuels
- Abstract
Marginal Abatement Cost Curves compare and assess greenhouse gas mitigation options available to various sectors of the economy. In the Irish agricultural sector, large anaerobic digestion facilities are currently considered a high-cost abatement solution. In prior studies of anaerobic digestion abatement costs, two options were assessed: the generation of heat and electricity from biogas (115 €/tCO
2eq ) and the production of renewable heat from biomethane (280 €/tCO2eq ). Both scenarios encompass single cost values that may not capture the potentially variable nature of such systems. In contrast, prior techno-economic analyses and lifecycle analyses can provide a comparison of the abatement costs of anaerobic digestion systems at a range of scales. This work compares two case studies (based on prior literature) for small and medium-scale on farm anaerobic digestion systems. The small-scale system is set in Ireland with cattle slurry collected in open tanks during the winter, while the medium-scale system is set in the USA with cattle slurry collected periodically indoors all year-round. It was found that the abatement cost can vary between -117 to +79 € per t CO2eq . The key variables that affected the abatement cost were additional revenue streams such as biofertilizer sales, displaced energy savings, and additional incentives and emissions savings within the system boundary. Including only some of these options in the analysis resulted in higher abatement costs being reported. Based on the variation between system topologies and therefore system boundaries, assigning a single mitigation cost to anaerobic digestion systems may not be representative.- Published
- 2023
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48. Examining Usability, Acceptability, and Adoption of a Self-Directed, Technology-Based Intervention for Upper Limb Rehabilitation After Stroke: Cohort Study.
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Broderick M, O'Shea R, Burridge J, Demain S, Johnson L, and Bentley P
- Abstract
Background: Upper limb (UL) recovery after stroke is strongly dependent upon rehabilitation dose. Rehabilitation technologies present pragmatic solutions to dose enhancement, complementing therapeutic activity within conventional rehabilitation, connecting clinicians with patients remotely, and empowering patients to drive their own recovery. To date, rehabilitation technologies have been poorly adopted. Understanding the barriers to adoption may shape strategies to enhance technology use and therefore increase rehabilitation dose, thus optimizing recovery potential., Objective: We examined the usability, acceptability, and adoption of a self-directed, exercise-gaming technology within a heterogeneous stroke survivor cohort and investigated how stroke survivor characteristics, technology usability, and attitudes toward technology influenced adoption., Methods: A feasibility study of a novel exercise-gaming technology for self-directed UL rehabilitation in early subacute stroke survivors (N=30) was conducted in an inpatient, acute hospital setting. Demographic and clinical characteristics were recorded; participants' performance in using the system (usability) was assessed using a 4-point performance rating scale (adapted from the Barthel index), and adherence with the system was electronically logged throughout the trial. The technology acceptance model was used to formulate a survey examining the acceptability of the system. Spearman rank correlations were used to examine associations between participant characteristics, user performance (usability), end-point technology acceptance, and intervention adherence (adoption)., Results: The technology was usable for 87% (n=26) of participants, and the overall technology acceptance rating was 68% (95% CI 56%-79%). Participants trained with the device for a median of 26 (IQR 16-31) minutes daily over an enrollment period of 8 (IQR 5-14) days. Technology adoption positively correlated with user performance (usability) (ρ=0.55; 95% CI 0.23-0.75; P=.007) and acceptability as well as domains of perceived usefulness (ρ=0.42; 95% CI 0.09-0.68; P=.03) and perceived ease of use (ρ=0.46; 95% CI 0.10-0.74; P=.02). Technology acceptance decreased with increased global stroke severity (ρ=-0.56; 95% CI -0.79 to -0.22; P=.007)., Conclusions: This technology was usable and acceptable for the majority of the cohort, who achieved an intervention dose with technology-facilitated, self-directed UL training that exceeded conventional care norms. Technology usability and acceptability were determinants of adoption and appear to be mediated by stroke severity. The results demonstrate the importance of selecting technologies for stroke survivors on the basis of individual needs and abilities, as well as optimizing the accessibility of technologies for the target user group. Facilitating changes in stroke survivors' beliefs and attitudes toward rehabilitation technologies may enhance adoption. Further work is needed to understand how technology can be optimized to benefit those with more severe stroke., (©Michelle Broderick, Robert O'Shea, Jane Burridge, Sara Demain, Louise Johnson, Paul Bentley. Originally published in JMIR Rehabilitation and Assistive Technology (https://rehab.jmir.org), 21.08.2023.)
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- 2023
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49. Does breast cancer policy meet the needs of Aboriginal and Torres Strait Islander women in Australia? a review.
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Christie V, Riley L, Green D, Snook K, Henningham M, Rambaldini B, Amin J, Pyke C, Varlow M, Goss S, Skinner J, O'Shea R, McCowen D, and Gwynne K
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- Humans, Female, Australian Aboriginal and Torres Strait Islander Peoples, Australia, Surveys and Questionnaires, Policy, Breast Neoplasms therapy, Health Services, Indigenous
- Abstract
Objective: To evaluate if existing Australian public policy related to screening, diagnosis, treatment and follow up care for breast cancer addresses the needs of and outcomes for Indigenous
1 women?, Methods: This review of policy employed a modified Delphi method via an online panel of experts (n = 13), who were purposively recruited according to experience and expertise. A series of online meetings and online surveys were used for data collection. The aims of the study were to: Identify all existing and current breast cancer policy in Australia; Analyse the extent to which consideration of Indigenous peoples is included in the development, design and implementation of the policy; and Identify policy gaps and make recommendations as to how they could be addressed. The policies were evaluated using 'A Guide to Evaluation under the Indigenous Evaluation Strategy, 2020'., Results: A list of current breast cancer policies (n = 7) was agreed and analysed. Five draft recommendations to improve breast cancer outcomes for Indigenous women were developed and refined by the panel., Conclusions: Current breast cancer policy in Australia does not address the needs of Indigenous women and requires change to improve outcomes., (© 2023. The Author(s).)- Published
- 2023
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50. "Everyone needs a Deb": what Australian indigenous women say about breast cancer screening and treatment services.
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Christie V, Green D, Skinner J, Riley L, O'Shea R, Littlejohn K, Pyke C, McCowen D, Rambaldini B, and Gwynne K
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- Female, Humans, Australia epidemiology, Early Detection of Cancer, Australian Aboriginal and Torres Strait Islander Peoples, Breast Neoplasms diagnosis, Breast Neoplasms therapy, Health Services, Indigenous
- Abstract
Background: Breast cancer continues to be the second most diagnosed cancer overall and the most diagnosed cancer for women in Australia. While mortality rates overall have declined in recent years, Indigenous women continue to be diagnosed at more marginal rates (0.9 times) and are more likely to die (1.2 times). The literature provides a myriad of reasons for this; however, the voices of Indigenous women are largely absent. This study sets out to understand what is happening from the perspectives of Australian Indigenous women with a view to charting culturally safer pathways that improve participation in screening and treatment by Indigenous women., Methods: This co-design study was conducted using semi-structured, in-depth interviews and focus group discussions. Recruitment of study participants was via snowball sampling. Participants were subsequently consented into the study through the Aboriginal Health Service and the research team. Interviews were audio recorded and transcribed verbatim, and data coded in NVivo12 using inductive thematic analysis., Results: A total of 21 Indigenous women and 14 health service providers were interviewed predominantly from the same regional/rural area in NSW, with a small proportion from other states in Australia. Six major themes were identified: Access, Awareness, Community and Family, Lack of control, Negative feelings and associations and Role of services., Conclusion: To improve access and participation of Indigenous women and ultimately improve mortality rates, breast cancer services must explicitly address cultural and community needs., (© 2023. The Author(s).)
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- 2023
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