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52. Selected abstracts

Author

Corkery, P. P., Leek, B. F., Caulfield, B., Garrett, M., Gormley, J. P., O’Donnell, P. M., Kennedy, N., Sayers, K., Stokes, E., Bresnihan, B., Fitzgerald, O., McGarvey, M. A., Tonra, M., Hooper, A. C. B., Barry, J., Maurer, B., Hussey, J., Gormley, J., Noble, J. G., Alves-Guerreiro, J., Lowe, A. S., Walsh, D. M., NicNiocaill, B., Harte, M., O’Connor, W. T., O’Hara, A. M., Orren, A., Moran, A. P., Hardiman, D. A., Lee, T. C., Croke, D. T., Tolan, R., McBennett, S., Warmington, S., McGuire, M., Bradford, A., O’Hare, T., MacDermott, M., Lynch, F., O’Regan, R. G., McLoughlin, P., Quinn, T., Ryan, J. P., Pickering, M., Campion, D. P., Jones, J. F. X., Ryan, S., McNicholas, W. T., Nolan, P., Doyle, F. J., Rackard, S. M., Beddy, P., Campbell, V. A., Bakhle, Y. S., Bell, C., Usher, C., Chan, L., Keenan, A. K., McQuaid, K. E., Cullen, V. C., Smith, E. M., Kelly, A., Lynch, M. A., Freir, D. B., Holscher, C., Herron, C. E., Pearson, H. A., Curran, B. P., O’Connor, J. J., Quinn, A., McHale, J., Moriarty, D., O’Connor, J., Glennon, J. C., Van Vliet, B. J., Long, S. K., Kruse, C., Gallagher, H. C., Bacon, C. L., Boland, B., Griffin, A. M., Preisler, J., O’Brien, L., Regan, C. M., Hurley, S., Kearney, P. J., Slevin, J., Barry-Kinsella, C., Ryan, C. A., Kllleen, O., Glllan, J., Clarke, T., Matthews, T., Corcoran, D., Dunn, E., Geary, M., O’Herlihy, C., Keane, D., Slattery, M. M., O’Leary, M. J., Morrison, J. J., Ryan, E., Gorman, W. A., Bourke, A., Larkin, J., Mayes, C., Jenkins, J., Ryan, M., Lalchandani, S., Sheil, O., Lynch, N., Costigan, C., Murphy, J. F., Bhatia, R., Foran, A., Donohue, V., McParland, P., LaSjaunais, P., Rodesch, G., McGinn, M., McAloon, J., O’Leary, M., Astbury, K., Harmon, D., Sharkey, A., Gaffney, G., O’Regan, G., McMahon, C., Murray, D., McDermott, C., Woolhead, E., Gillan, J., Cartmill, J. L., Harper, M. A., Al-Shabibi, N., Hanahoe, M., Wingfield, M., Larkin, J. A. M., Bell, A. H., McClure, B. G., Sweeney, L., Martin, D. H., O’Donoghue, P., Davoren, A., Lucas, G. F., McKiernan, J., Gallagher, D. M. T., Dunne, K. P., Fulena, O., Sheridan, M., Griffin, E., White, M., Deasy, P., O’Riordan, M., O’Gorman, C., Mongan, C., McCafferkey, M., Henry, G., McKenna, P., O’Malley, A., Devaney, D., Kelleghan, P., Mooney, E. E., Gillan, J. E., Fitzpatrick, M., McQuillan, K., Heffron, C., Hodnett, P., Curtain, A., O’Connor, T. C. F., Connell, T. G., Waldron, D., Gorman, W., Bolger, T., O’Keefe, M., Murphy, J., Dolan, L. M., Traub, A. I., Slattery, M. M., O’Leary, M. J., Curley, A. E., Halliday, H. L., Tubman, T. R. J., Kileen, O., Riadha, H., Russell, J., Philips, R., Regan, C., Ali, I., Coughlan, A. C. J., Turner, M. J., Smith, A., O’Flanagan, D., Igoe, D., Ryan, F., Forde, D., McArdle, E., Ko, D., Bedford, D., Hegarty, M., Dunlevy, B., Corcoran, R., Holohan, T., Feeney, A., McGee, H., Shannon, W., Condon, M., Hyland, C., Sayers, G., Feely, E., Crowley, D., O’Reilly, D., O’Connell, T., Cronin, M., Johnson, H., Fitzgeraldi, M., Cafferkey, M., Breslin, A., Bonner, C. J., Foley, B., Fitzgerald, M., Wall, P. G., McNamara, E., Costigan, P., Prendergast, T., Foye, K., Cosgrove, C., Keane, A., Murphy, E., O’Donnell, J., Quinlan, A., Thornton, L., Roch, E. A., Lyons, R. A., Maddocks, A., Barnes, P., Price, L., McCabe, M., Nash, P., Midha, A., Doyle, Y., Kilgallen, A., Wright, P., Ryan, T., De La Harpe, D., Harkins, V., Brennan, C., O’Connell, V., Evans, D. S., Ni Mhuircheartaigh, J., O’Donnell, J. M., Rhatigan, A., Shelley, E., Collins, C., Byrne, M., Murphy, A. W., Plunkett, P. K., Murray, A., Bury, G., Lynam, F., McMahon, G., Greally, T., Kane, D., Veale, D., Reece, R., Busteed, S., Bennett, M. W., Stone, M., Molloy, C., O’Connell, J., Molloy, M. G., Shanahan, F., Guerin, J., Casey, E., Feighery, C., Lin, F., Jackson, J., Pendleton, A., Wright, G. D., Hughes, A. E., O’Gradaigh, D., Debham, I., Compston, J., McEvoy, A., Murphy, E. P., Salonen, D., Payne, P., Lax, M., Lapp, V., Inman, R., O’Rourke, K., Brennan, D., Harty, J., McCarthy, C., O’Byrne, J., Eustace, S., Chirayath, H., Liggett, N. W., Morgan, M. P., Fitzgerald, D. J., McCarthy, C. J., McCarthy, G. M., Lee, R. Z., Wai, K., Nevin, D., Leary, A. O., Lee, R., Leary, A. O., Casey, E. B., Leary, A. O., O’Leary, A., Breen, D., Tuite, D., McInerney, D., Sim, R., Frederic, A. L., Smith, O., White, B., Murphy, M., Silke, C., O’Keeffe, E., Fanning, N., Spence, L., Parfrey, N. A., McConnell, J. R., Crockard, A. D., Cairns, A. P., Bell, A. L., Kavanagh, O., Moyes, D. A., Finch, M., Rooney, M., Bell, A., Founas, I., El-Magbri, A., Mooney, S., Kennedy, M., Coughlan, R. J., Ramakrishnan, S. A., Gsel, A., Finnerty, O., Burns, M., Yateman, M., Camaco-Hubner, C., Matthews, C. F., Taggart, A., Fuller, K., Murphy, M. S., Phelan, M., Murphy, T. B., Wynne, F., Quane, K., Daly, M., O’Leary, J., da Silva, I., Bermingham, N., Gogarty, M., Gallagher, L. P., O’Hara, R., Godson, C., Brady, H., Osman, H., El-Rafie, A., Foley-Nolan, D., Kirwan, P., Corcoran, O., Duffy, T., Drummond, F., Madigan, A., Williams, D., Gallagher, P., Hatton, C., Cunningham, S., FitzGerald, O., Minnock, P., Wylie, E., Egan, D., Mc Cormack, J., Shea, M. O., Evans, D., O’Lorcain, P., Comber, H., Evans, A., Jones, J., Garavan, C., Kelleher, K., Boland, M. C., Healy, R., O’Sullivan, M. B., Burke, M., Mc Donald, P., Smithson, R., Glass, J., Mason, C. A., Mullins, N., Nolan, D., McCormick, P., Coughlan, S., Dooley, S., Kelleher, C. C., Hope, A., Murphy, F., Barry, M., Sixsmith, J., MacFarlane, A., MacLeod, C., McElroy, G., O’Loan, D., Kennedy, F., Kerr, R. M., Lim, J., Allwright, S. P. A., Bradley, F. L., Barry, J. M. G., Long, J., Parry, J. V., Creagh, D., Perry, I. J., Collins, A., Neilson, S., Colwell, N., O’Halloran, D., O’Neill, S., McErlain, S., Okasha, M., Gaffney, B., McCarron, P., Hinchion, R., Drew, C., Gavin, A., Fitzpatrick, D., Campbell, R., Wannamethee, S. G., Shaper, A., Friel, S., Kelleher, C., Kee, F., Atterson, C. C., Wilson, E. A., McConnell, J. M., Wheeler, S. M., Watson, J. D., Norashikin Rahman, N., Sheehan, J., Wall, C., Kelleher, B., O’Broin, S. D., Mullan, R. N., McKeveney, P. J., Hodges, V. M., Winter, P. C., Maxwell, P., Simpson, D. A., Lappin, T. R. J., Maxwell, A. P., Eustace, J. A., Coresh, J., Kutchey, C., Te, P. L., Gimenez, L. F., Scheel, P. J., Walser, M., McMahon, R. A., Clarkson, M., Martin, F., Brady, H. R., Blake, C., O’Meara, Y. M., Gupta, S., MacKenzie, H., Doyle, S., Fotheringham, T., Haslam, P., Logan, M. P., Conlon, P., Lee, M., Maderna, P., Cottell, D. C., Mitchell, S., Gulmann, C., Østerby, R., Bangstad, H. J., Rljdberg, S., Dempsey, M., Nathwani, S., Ryan, M. P., McMahon, B., Stenson, C., Murtagh, H., Brown, J. H., Doran, P., McGinty, A., Little, M. A., O’Brien, E., Owens, P., Holian, J., Mee, F., Walshe, J. J., Omer, S. A., Power, D., Diamond, P., Watson, R. W., Shahsafei, A., Jiang, T., Brenner, B. M., Mackenzie, H. S., Neary, J., Dorman, A., Keoghan, M., Campbell, E., Walshe, J., Little, M., Nee, L., O’Ceallaigh, C., McGlynn, H., Bergin, E., Garrett, P. J., Keane, T., Gormley, G., Watson, A., Atta, M. G., Perl, T. M., Song, X., Healy, E., Leonard, M., Lynch, J., Watson, A. J., Lappin, D., Lappin, D. W. P., Hannan, K., Burne, M., Daniels, F., Rabb, H., McBride, B., Kieran, N., Shortt, C., Codd, M., Murray, F., McCormack, A., Brown, C., Wong, C., Dorman, A. M., Keogan, M., Donohue, J., Farrell, J., Donohoe, J., O’Broin, S., Balfe, A., Mellotte, G. J., Abraham, K. A., McGorrian, C., Wood, A. E., Neligan, M., Kelly, B. D., Finnegan, P., Cormican, M., Callaghan, J., Crean, J. K. G., Moffitt, T. A., Devlin, H. L., Garrett, P. J., Soosay, A., O’Neill, D., Counihan, A., Hickey, D., Keogan, M. T., Harvey, K., O’Riordan, E., Waldek, S., Kalra, P. A., O’Donoghue, D. J., Foley, R. N., O’Riordan, A., Kelliher, D., Mellotte, G., Giblin, L., Keogh, J. A. B., O’Connell, M., O’Meara, A., Breatnach, F., Gillick, J., Tazawa, H., Puri, P., Molloy, E., O’Neill, A. J., Sheridan-Pereira, M., Fitzpatrick, J. M., Webb, D. W., Watson, R. W. G., Linnane, B., O’Donnell, C., Clarke, T. A., Martin, C., McKay, M., McBrien, J., Glynn, F., O’Donovan, C., Hall, W. W., Smith, J., Khair, K., Liesner, R., Hann, I. M., Smith, O. P., Gallagher, S., Mahony, M. J., Hilal, A., Cosgrove, J. F., Monaghan, C., Craig, B., Al-Hassan, A., Walsh, K., Duff, D., Slizlok, P. O., Halahakoon, C., MacPherson, C., McMillan, S., Dalzell, E. E., McCaughan, J., Redmond, A. O. B., DeCaluwe, D., Yoneda, A., Akl, U., Dempsey, E., Farrell, M., Webb, D., Elabbas, A., Fox, G., Gormally, S., Grant, B., Corkey, C. W. B., Nicholson, A., Murphy, A., O’Grady, P., Barry, O., Macpherson, C., Stewart, M. C., Alderdice, F., Matthews, T. G., McDonnell, M., McGarvey, C., O’Regan, M., Ní Chróinín, M., Tormey, P., Ennis, S., Green, A. J., Abbas, S., O’Marcaigh, A., Conran, M., Crushell, E., Saidi, A., Curran, P., Donoghue, V., King, M. D., Elnazir, B., Leonard, J., Kavanagh, C., Brown, D., Corrigan, N., McCord, B., Quinn, M., O’Connell, L., Mcdonagh, B., Awan, A., Gill, D., Kakkar, R., Sweet, D. G., Warner, J. A., O’Connor, C., Herzig, M., Twomey, A., White, M. J., Sweeney, B., Surana, R., Hodgson, A., Rafferty, M., Livingstone, W., Peake, D., Wassemer, E., Whitehouse, W., Abdullah, N., Al-Hassan, A., Oslizlok, P., O’Connell, N., Balding, J., Livingstone, W. J., Healy, M., Mynett-Johnson, L., McAllister, I., Dick, A. C., Herron, B., Boston, V. E., Callaghan, C. O., Brien, D. O., Walsh, A., Philip, M., McShane, D., Hoey, M. C. V., Sharif, F., McDermott, M., Dillon, M., Drumm, B., Rowland, M., Imrie, C., Kelleher, S., Bourke, B., Iqbal, M., Ziedan, Y., O’Neill, M., O’Riordan, S., Basheer, S. M. B., O’Callaghan, S., Chong, A., Kelly, M., Nicholson, A. J., Cooke, R., Sreenan, C., Fallon, M., Denham, B., Dowding, V., Cussen, G., McManus, V., Hensey, O., Monaghan, H., Basheer, S. N., Quinn, E., Hoey, H. M. C. V., Mohamed, S., Ramesh, R. R., Mayne, P., Tracy, E., Gormally, S. M., Curtis, E., McCallion, N., Watson, R., O’Mahony, O., Keegan, M., Ward, K., Barton, D., Poulton, J., Treacy, E., Honour, J., deCaluwe, D., Ni Chróinín, M., Cosgrove, J., Chaudhry, T. S., Long, N. M., Lynch, B., Lasjaunais, P., McDonald, D. G. M., McMenamin, J. B., Farrell, M. J., Roche, E. F., Menon, A., Buckley, C., Mackey, A., Ohlandieck, K., Das, A., Reilly, D., Killeen, O., Harper, J., Roche, E., Hoey, H., Caird, J., O’Brien, D., Allcutt, D., Farrington, N., Murphy, J. F. A., Savage, J. M., Sands, A. J., Casey, F. A., Craig, B. G., Dornan, J. C., Johnston, J., Patterson, C., Lynch, C., Mulholland, H. C., Watkins, D. C., Young, I., Cran, G., Boreham, C. A. G., McCallion, W. A., Clements, N. F., Stevenson, M. R., Macpherson, C., O’Donoghue, D., Jenkins, L., Thompson, A. J., Shields, M. D., Taylor, R. T., Kerr, R., Hughes, J. L., Stewart, M., Jackson, P., Fitzpatrick, C., Rasheed, M., Colhoun, E., Bailie, A. G., Gray, S., Brown, S., Curley, A., Sweet, D. G., MacMahon, K. J., O’Connor, C. M., Nichelson, A., Lynch, N. E., Finch, D., Foley, M., Scallan, E., Dillon, B., Lyons, S., O’Loughlin, R., Ward, M., Nally, R., Harkin, A., Kelly, J. P., Leonard, B. E., Nic Niocaill, B., Magee, P., Connor, T. J., Shen, Y., McCullough, G. R., McDonough, S. M., Nic Niocaill, B., Cramp, A. F. L., Hynes, M., Corkery, P., Carey, M., McGarrigle, D., Higgins, S., Murray, H., Moran, C. J., Dennedy, M. C., Brosnan, J., Morris, L., Sheppard, B. L., Black, A., Wilkins, B., Folan-Curran, J., Skelton, K., Owens, M., Nemeroff, C., Houlihan, D., O’Keeffe, C., Nolan, N., McCormick, P. A., Baird, A. W., Raducan, I., Corcoran, P., Brennan, R., Molloy, P., Friel, A., Maher, M., Glennon, M., Smith, T., Nolan, A., Houghton, J. A., Carroll, O., Colleran, S., O’Cuinn, G., Snow, H. M., O’Regan, D., Markos, H. F., Pollock, K., Cannon, D. M., McBean, G., O’Riordan, A., Quinlan, L. R., Kane, M. T., Higglns, B. D., Moriarty, D. M., Fitzgerald, D., Katkada, A., Canny, G., MacMathuna, P., O’Donoghue, D., O’Donovan, M. M., Schuur, A. G., Murphy, K. J., Foley, A. G., ten Bruggencate, S. J. M., and Ireland, L.

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57. Some excavations on the line of the Antonine Wall 1985-93

Author

Keppie, Lawrence J F, primary, Bailey, Geoff B, primary, Dunwell, Andrew J, primary, McBrien, J H, primary, Speller, Keith, primary, Bateson, J D, primary, Boardman, S, primary, Dickson, C, primary, Henig, M, primary, Tipping, R, primary, and Webster, P V, primary

Published
1996
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58. Service Learning in Preparation to Teach Global Students.

Author

McBrien, J. Lynn

Subjects
UNITED States emigration & immigration, IMMIGRANT children, FOREIGN students, SERVICE learning, TRANSFORMATIVE learning, TWELFTH grade (Education), EDUCATION
Abstract

Immigration trends in the United States necessitate the preparation of new K-12 teachers to teach diverse populations and to recognize the capabilities of immigrant and refugee children. Transformative learning that results from service learning offers a promising opportunity for preservice teachers to gain awareness and change their attitudes toward these children. This study examined the role of service learning where undergraduate education students tutored at a local refugee agency or elementary school. an analysis of their journal entries indicated changes in beliefs and attitudes toward refugee and other immigrant children, including the acknowledgement of their motivation and determination when confronted by challenges not faced by students born in the United States. [ABSTRACT FROM AUTHOR]

Published
2008
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59. Research and practice hand in hand: the experience of promoting research of benefit to people with learning disabilities from within the NHS.

Author

McBrien J

Abstract

The paper describes how clinicians from different disciplines and agencies working with children and adults with learning disabilities have joined forces to promote and conduct research pertinent to this client group. Examples of research projects show how practitioners can improve the evidence base and service delivery. Difficulties for practitioners in conducting research and gaining funding are described, with reference to the recommendations of the Cooksey report (2006). [ABSTRACT FROM AUTHOR]

Published
2008

62. Issues in the Training and Evaluation of Behaviour Modification Skills for Staff Working with Profoundly Retarded Multiply Handicapped Children.

Author

Hogg, J., Foxen, T., and McBrien, J.

Abstract

Kiernan and Riddick's programme for training operant techniques was employed to teach behaviour modification to a variety of staff in a children's mental handicap hospital. The aim was to evaluate the course in relation to a carefully defined group of profoundly retarded multiply handicapped children. Evaluation of the course is described and significant improvement in trainees' skills with respect to the use of physical prompting and reinforcement noted. Some problems of staff in implementing the learnt technique are considered. Finally, the relation between the applicability of behavioural techniques and the characteristics of profoundly retarded multiply handicapped children is considered in the light of more detailed studies of their learning characteristics. [ABSTRACT FROM PUBLISHER]

Published
1981
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63. A Second Chance for Refugee Students.

Author

McBrien, J. Lynn

Subjects
*REFUGEES, *UNITED States education system, *PARENT participation in education, *STUDENTS
Abstract

Presents support strategies for the success of educating refugee students in the U.S. Difficulties faced by refugee students; Use of literature from students' countries of origin; Reasons for the lack of refugee parents' involvement in education.

Published
2003

65. Letters.

Author

Crowley, Joan Frances, Henderson, Betty, Farmer, Anna, Wagner, David, Sanders, Deborah M., Tripoli, Joel, Upton, Jay, Stewart, Norman, Prutschi, Manuel, Lupinin, N., Oglesbee, Frank W., and McBrien, J. Robert

Subjects
LETTERS to the editor, PSYCHIATRIC hospitals, SEX work
Abstract

Presents letters to the editor referencing articles and topics discussed in previous issues. Praise for the article on scholar Sir Arnold Lunn; "Psychiatry, KGB Style," which reported on Soviet mental hospitals; "The History of Legalized Prostitution, 1984-2004," which discussed the legal right to practice prostitution.

Published
1974

66. The Face of Terrorism: Policymaking and the Eye of the Beholder

Author

DEPARTMENT OF THE TREASURY WASHINGTON DC, McBrien,J. R., DEPARTMENT OF THE TREASURY WASHINGTON DC, and McBrien,J. R.

Abstract

According to the Department of State, in the last 5 years there have been 1,559 international terrorist incidents involving U.S. citizens and property as targets. These incidents include the Beirut Marine barracks bombing. In that period, 312 U.S. citizens have been killed and 212 wounded. In the period 1973 through 1982, the total numbers of international victims of terrorism have been 3,500 killed and 7,600 wounded. Bombing have fluctuated in the 50 to 75 percent ranges as the cause of terrorist acts each year, and more than a third of deaths from terrorist acts have been attributed to bombing. Now, decisionmakers-and not only those who sit at the very top at the National Security Council level, but also those at other levels-have to ask questions: What is terrorism? How do you define it? When does a specific act fit within definitions, and when doesn't it? How does the government protect against that specific kind of act? Furthermore, they must think about the institutions they are dealing with, because they need to know not only how to govern their own troops and run their own agencies, but also how these other pepole, who should be having an interplay with them, approach the subject. My view is that we have basically five institutional perspectives: diplomatic, intelligence, law enforcement, military, and security., This article is from 'Proceedings of the Annual Symposium on the Role of Behavioral Science in Physical Security (9th) - Symmetry and Asymmetry of Global Adversary Behavior Held at Springfield, Virginia on 3-4 April 1984,' AD-A152 459, p21-26.

Published
1984

68. Cultural and academic adjustment of refugee youth: Introduction to the special issue

Author

McBrien J., Dooley K., Birman D., McBrien J., Dooley K., and Birman D.

Abstract

© 2017 Elsevier Ltd In this introduction to the IJIR special issue on refugee youth in academic settings, the editors sought manuscripts that examined both challenges and effective practices in countries of temporary and permanent refugee resettlement. We welcomed diverse methodological approaches and empirical work at all levels and types of education (formal, non-formal, and informal). Our final selections do not fully represent the field of refugee education, as eight of the nine are studies in third countries of permanent resettlement, a designation received by only about one percent of the total refugee population. Perspectives came from the social sciences: psychology, sociology, anthropology, and sociolinguistic disciples. Themes of the articles fall into two broad categories: 1) educational challenges due to trauma, acculturation stressors, and educational issues; and 2) educational practices intended to address some of these challenges. Although the resettlement category is the smallest of the UNHCR's “durable solutions,” the authors present important findings to support refugee students’ success. These have to do with collaborative processes, issues of identity, the use of social media, and teacher training in multicultural and language support. In considering future work in this field, we conclude that dimensions of justice need to be more fully examined in other refugee solutions (such as repatriation and local integration in the first country of refuge). We recommend that more research be conducted on the current European “migrant crisis.” We also call for scholars to be public intellectuals in venues that can reframe the characterization of refugees in opposition to “fake news” fanning public fears.

69. Cultural and academic adjustment of refugee youth: Introduction to the special issue

Author

McBrien J., Dooley K., Birman D., McBrien J., Dooley K., and Birman D.

Abstract

© 2017 Elsevier Ltd In this introduction to the IJIR special issue on refugee youth in academic settings, the editors sought manuscripts that examined both challenges and effective practices in countries of temporary and permanent refugee resettlement. We welcomed diverse methodological approaches and empirical work at all levels and types of education (formal, non-formal, and informal). Our final selections do not fully represent the field of refugee education, as eight of the nine are studies in third countries of permanent resettlement, a designation received by only about one percent of the total refugee population. Perspectives came from the social sciences: psychology, sociology, anthropology, and sociolinguistic disciples. Themes of the articles fall into two broad categories: 1) educational challenges due to trauma, acculturation stressors, and educational issues; and 2) educational practices intended to address some of these challenges. Although the resettlement category is the smallest of the UNHCR's “durable solutions,” the authors present important findings to support refugee students’ success. These have to do with collaborative processes, issues of identity, the use of social media, and teacher training in multicultural and language support. In considering future work in this field, we conclude that dimensions of justice need to be more fully examined in other refugee solutions (such as repatriation and local integration in the first country of refuge). We recommend that more research be conducted on the current European “migrant crisis.” We also call for scholars to be public intellectuals in venues that can reframe the characterization of refugees in opposition to “fake news” fanning public fears.

79. CD8 lymphocyte depletion enhances the latency reversal activity of the SMAC mimetic AZD5582 in ART-suppressed SIV-infected rhesus macaques.

Author

Mavigner M, Liao LE, Brooks AD, Ke R, Mattingly C, Schoof N, McBrien J, Carnathan D, Liang S, Vanderford TH, Paiardini M, Kulpa D, Lifson JD, Dunham RM, Easley KA, Margolis DM, Perelson AS, Silvestri G, and Chahroudi A

Abstract

Inducing latency reversal to reveal infected cells to the host immune system represents a potential strategy to cure HIV infection. In separate studies, we have previously shown that CD8 + T cells may contribute to the maintenance of viral latency and identified a novel SMAC mimetic/IAP inhibitor (AZD5582) capable of reversing HIV/SIV latency in vivo by activating the non-canonical (nc) NF-κB pathway. Here, we use AZD5582 in combination with antibody-mediated depletion of CD8α + cells to further evaluate the role of CD8 + T cells in viral latency maintenance. Six rhesus macaques (RM) were infected with SIVmac239 and treated with ART starting at week 8 post-infection. After 84-85 weeks of ART, all animals received a single dose of the anti-CD8α depleting antibody (Ab), MT807R1 (50mg/kg, s.c.), followed by 5 weekly doses of AZD5582 (0.1 mg/kg, i.v.). Following CD8α depletion + AZD5582 combined treatment, 100% of RMs experienced on-ART viremia above 60 copies per ml of plasma. In comparator groups of ART-suppressed SIV-infected RMs treated with AZD5582 only or CD8α depletion only, on-ART viremia was experienced by 56% and 57% of the animals respectively. Furthermore, the frequency of increased viremic episodes during the treatment period was greater in the CD8α depletion + AZD5582 group as compared to other groups. Mathematical modeling of virus reactivation suggested that, in addition to viral dynamics during acute infection, CD8α depletion influenced the response to AZD5582. This work suggests that the latency reversal induced by activation of the ncNF-κB signaling pathway with AZD5582 can be enhanced by CD8α + cell depletion., (Copyright © 2021 Mavigner et al.)

Published
2021
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80. Virologic and Immunologic Features of Simian Immunodeficiency Virus Control Post-ART Interruption in Rhesus Macaques.

Author

Strongin Z, Micci L, Fromentin R, Harper J, McBrien J, Ryan E, Shenvi N, Easley K, Chomont N, Silvestri G, and Paiardini M

Subjects
Animals, CD4-CD8 Ratio, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, DNA, Viral blood, DNA, Viral immunology, Macaca mulatta, Time Factors, Anti-Retroviral Agents pharmacology, Simian Acquired Immunodeficiency Syndrome blood, Simian Acquired Immunodeficiency Syndrome drug therapy, Simian Acquired Immunodeficiency Syndrome immunology, Simian Immunodeficiency Virus immunology, Simian Immunodeficiency Virus metabolism, Th17 Cells immunology, Th17 Cells metabolism
Abstract

Antiretroviral therapy (ART) cannot eradicate human immunodeficiency virus (HIV) and a rapid rebound of virus replication follows analytical treatment interruption (ATI) in the vast majority of HIV-infected individuals. Sustained control of HIV replication without ART has been documented in a subset of individuals, defined as posttreatment controllers (PTCs). The key determinants of post-ART viral control remain largely unclear. Here, we identified 7 SIV mac239 -infected rhesus macaques (RMs), defined as PTCs, who started ART 8 weeks postinfection, continued ART for >7 months, and controlled plasma viremia at <10 4 copies/ml for up to 8 months after ATI and <200 copies/ml at the latest time point. We characterized immunologic and virologic features associated with post-ART SIV control in blood, lymph node (LN), and colorectal (RB) biopsy samples compared to 15 noncontroller (NC) RMs. Before ART initiation, PTCs had higher CD4 T cell counts, lower plasma viremia, and SIV-DNA content in blood and LN compared to NCs, but had similar CD8 T cell function. While levels of intestinal CD4 T cells were similar, PTCs had higher frequencies of Th17 cells. On ART, PTCs had significantly lower levels of residual plasma viremia and SIV-DNA content in blood and tissues. After ATI, SIV-DNA content rapidly increased in NCs, while it remained stable or even decreased in PTCs. Finally, PTCs showed immunologic benefits of viral control after ATI, including higher CD4 T cell levels and reduced immune activation. Overall, lower plasma viremia, reduced cell-associated SIV-DNA, and preserved Th17 homeostasis, including at pre-ART, are the main features associated with sustained viral control after ATI in SIV-infected RMs. IMPORTANCE While effective, antiretroviral therapy is not a cure for HIV infection. Therefore, there is great interest in achieving viral remission in the absence of antiretroviral therapy. Posttreatment controllers represent a small subset of individuals who are able to control HIV after cessation of antiretroviral therapy, but characteristics associated with these individuals have been largely limited to peripheral blood analysis. Here, we identified 7 SIV-infected rhesus macaques that mirrored the human posttreatment controller phenotype and performed immunologic and virologic analysis of blood, lymph node, and colorectal biopsy samples to further understand the characteristics that distinguish them from noncontrollers. Lower viral burden and preservation of immune homeostasis, including intestinal Th17 cells, both before and after ART, were shown to be two major factors associated with the ability to achieve posttreatment control. Overall, these results move the field further toward understanding of important characteristics of viral control in the absence of antiretroviral therapy., (Copyright © 2020 American Society for Microbiology.)

Published
2020
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81. A Response to: “A Cluster of Paediatric Invasive Group A Streptococcal and Chicken Pox Infections”

Author

Cassidy A and McBrien J

Subjects
Child, Child, Preschool, Female, Herpesvirus 3, Human immunology, Humans, Infant, Length of Stay, Male, Time Factors, Viral Vaccines, Chickenpox complications, Chickenpox epidemiology, Chickenpox prevention & control, Chickenpox therapy, Streptococcal Infections complications, Streptococcal Infections epidemiology, Streptococcal Infections therapy, Streptococcus pyogenes
Abstract

Competing Interests: The authors have no conflicts of interest to declare

Published
2018

82. Author's reply.

Author

Sheehan R, Eady N, Rantell K, Sinai A, Bernal J, Bohnen I, Bonell S, Courtenay K, Dodd K, Gazizova D, Hassiotis A, Hillier R, McBrien J, Mukherji K, Naeem A, Perez-Achiaga N, Sharma V, Thomas D, Walker Z, McCarthy J, and Strydom A

Subjects
Cholinesterase Inhibitors, Cohort Studies, Humans, Memantine, Dementia, Down Syndrome
Published
2018
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84. Impact of cholinesterase inhibitors or memantine on survival in adults with Down syndrome and dementia: clinical cohort study.

Author

Eady N, Sheehan R, Rantell K, Sinai A, Bernal J, Bohnen I, Bonell S, Courtenay K, Dodd K, Gazizova D, Hassiotis A, Hillier R, McBrien J, Mukherji K, Naeem A, Perez-Achiaga N, Sharma V, Thomas D, Walker Z, McCarthy J, and Strydom A

Subjects
Aged, Cohort Studies, Comorbidity, Female, Humans, Male, Middle Aged, Alzheimer Disease drug therapy, Alzheimer Disease mortality, Cholinesterase Inhibitors pharmacology, Down Syndrome drug therapy, Down Syndrome mortality, Excitatory Amino Acid Antagonists pharmacology, Memantine pharmacology
Abstract

Background: There is little evidence to guide pharmacological treatment in adults with Down syndrome and Alzheimer's disease. Aims To investigate the effect of cholinesterase inhibitors or memantine on survival and function in adults with Down syndrome and Alzheimer's disease., Method: This was a naturalistic longitudinal follow-up of a clinical cohort of 310 people with Down syndrome diagnosed with Alzheimer's disease collected from specialist community services in England., Results: Median survival time (5.59 years, 95% CI 4.67-6.67) for those on medication (n = 145, mainly cholinesterase inhibitors) was significantly greater than for those not prescribed medication (n = 165) (3.45 years, 95% CI 2.91-4.13, log-rank test P<0.001). Sequential assessments demonstrated an early effect in maintaining cognitive function., Conclusions: Cholinesterase inhibitors appear to offer benefit for people with Down syndrome and Alzheimer's disease that is comparable with sporadic Alzheimer's disease; a trial to test the effect of earlier treatment (prodromal Alzheimer's disease) in Down syndrome may be indicated. Declaration of interest A.S. has undertaken consulting for Ono Pharmaceuticals, outside the submitted work. Z.W. has received a consultancy fee and grant from GE Healthcare, outside the submitted work.

Published
2018
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85. Predictors of Age of Diagnosis and Survival of Alzheimer's Disease in Down Syndrome.

Author

Sinai A, Mokrysz C, Bernal J, Bohnen I, Bonell S, Courtenay K, Dodd K, Gazizova D, Hassiotis A, Hillier R, McBrien J, McCarthy J, Mukherji K, Naeem A, Perez-Achiaga N, Rantell K, Sharma V, Thomas D, Walker Z, Whitham S, and Strydom A

Subjects
Age of Onset, England epidemiology, Female, Humans, Male, Middle Aged, Risk Factors, Survival Analysis, Alzheimer Disease epidemiology, Down Syndrome complications
Abstract

Background: People with Down syndrome (DS) are an ultra-high risk population for Alzheimer's disease (AD). Understanding the factors associated with age of onset and survival in this population could highlight factors associated with modulation of the amyloid cascade., Objective: This study aimed to establish the typical age at diagnosis and survival associated with AD in DS and the risk factors associated with these., Methods: Data was obtained from the Aging with Down Syndrome and Intellectual Disabilities (ADSID) research database, consisting of data extracted from clinical records of patients seen by Community Intellectual Disability Services (CIDS) in England. Survival times when considering different risk factors were calculated., Results: The mean age of diagnosis was 55.80 years, SD 6.29. Median survival time after diagnosis was 3.78 years, and median age at death was approximately 60 years. Survival time was associated with age of diagnosis, severity of intellectual disability, living status, anti-dementia medication status, and history of epilepsy. Age at diagnosis and treatment status remained predictive of survival time following adjustment., Conclusion: This study provides the best estimate of survival in dementia within the DS population to date, and is in keeping with previous estimates from smaller studies in the DS population. This study provides important estimates and insights into possible predictors of survival and age of diagnosis of AD in adults with DS, which will inform selection of participants for treatment trials in the future.

Published
2018
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87. The application of differential ratings of perceived exertion to Australian Football League matches.

Author

Weston M, Siegler J, Bahnert A, McBrien J, and Lovell R

Subjects
Accelerometry, Adult, Australia, Dyspnea physiopathology, Geographic Information Systems, Humans, Leg physiology, Workload, Young Adult, Football physiology, Physical Exertion physiology
Abstract

Objectives: To investigate the application of differential ratings of perceived exertion for the examination of internal load during Australian Football League (AFL) matches., Design: Single cohort, observational study., Methods: Using the centiMax rating of perceived exertion (RPE) scale, 26 professional AFL players provided ratings for match exertion (RPE-M), along with differential ratings for breathlessness (RPE-B), leg exertion (RPE-L), and technical demand (RPE-T) following 129 matches (5.0 ± 1.6 matches per player). Global positioning satellite (GPS) and accelerometer measures were also collected. Data were analysed using magnitude-based inferences., Results: RPE scores were 93.0 ± 8.2 AU (RPE-M), 89.0 ± 11.0 AU (RPE-B), 91.5 ± 9.8 AU (RPE-L), and 87.0 ± 10.0 AU (RPE-T). There was a most likely small difference between RPE-L and RPE-T (5.5%; ± 90% confidence limits 1.9%), a likely small difference between RPE-L and RPE-B (3.5%; ± 1.5%) and a possibly small difference between RPE-B and RPE-T (1.9%; ± 1.9%). Within-player correlations between RPE and GPS measures were small for RPE-M (r = 0.14-0.28), unclear to small for RPE-B (r = 0.06-0.24) and unclear to moderate for RPE-L (r = 0.06-0.37). Differential RPE's combined to explain 76% of the variance in RPE-M. For all RPE scores, within-player variability was moderate to high (typical error: 7.9-12.4%), and the thresholds for a likely between-match change were 8.8-13.7%., Conclusions: As differential RPE's represent distinct sensory inputs, the collection of these scores facilitate the interpretation of internal match loads and therefore represent a valuable addition to match data collection procedures. Moderate to high within-player variability should be considered when interpreting between-match changes in all RPE scores., (Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Published
2015
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88. Meeting the health care needs of school-age children with intellectual disability.

Author

McBrien J and Macken S

Subjects
Adult, Child, Child, Preschool, Comorbidity, Developmental Disabilities epidemiology, Developmental Disabilities rehabilitation, Disability Evaluation, Female, Health Services Accessibility, Humans, Intellectual Disability epidemiology, Ireland epidemiology, Male, Prevalence, Risk Factors, Students, Young Adult, Disabled Persons rehabilitation, Health Services Needs and Demand, Intellectual Disability rehabilitation, Schools
Abstract

Intellectual disability (ID) is common and is known to affect 1-3% of the population. There is a lack of medical epidemiological data in Ireland for this group. Such data is necessary in providing the evidence base to plan for rehabilitation services, provide ongoing health care and consider prevention strategies. We report on the underlying diagnosis and co-morbidities of the school-age children in one Health Service Executive area. There were 97 children. Forty seven (48.5%) of the children have a chromosomal or genetic explanation for their disability, 16 (16.5%) have an environmental cause and 34 (35%) have no identified cause. The children have complex medical needs: 35 (36%) have epilepsy and 34 (35%) have gastro-intestinal problems; 24 (25%) have a respiratory condition and 15 (15%) have congenital heart disease. Thirty one (32%) and 30 (31%) have visual and hearing impairment respectively. Expansion of the National Intellectual Disability Database should be explored to include the medical epidemiological data to inform the future development of services for Intellectually Disabled.

Published
2009

89. Further case of microdeletion of 8q24 with phenotype overlapping Langer-Giedion without TRPS1 deletion.

Author

McBrien J, Crolla JA, Huang S, Kelleher J, Gleeson J, and Lynch SA

Subjects
Adipose Tissue abnormalities, Child, Preschool, Humans, In Situ Hybridization, Fluorescence, Karyotyping, Langer-Giedion Syndrome diagnostic imaging, Male, Oligonucleotide Array Sequence Analysis, Phenotype, Radiography, Repressor Proteins, Toes abnormalities, Chromosome Deletion, Chromosomes, Human, Pair 8 genetics, DNA-Binding Proteins genetics, Langer-Giedion Syndrome diagnosis, Langer-Giedion Syndrome genetics, N-Acetylglucosaminyltransferases genetics, Transcription Factors genetics
Abstract

Langer-Giedion syndrome results from a microdeletion at 8q24.1 encompassing the EXT1 and the adjacent TRPS1 gene. We report on a boy with an oligo array-cgh characterized small microdeletion involving EXT1 alone but with some features of Langer-Giedion syndrome suggesting a functional disturbance of TRPS1. This boy, in addition to a mild Langer-Giedion like phenotype, also had some unusual features including prominent toe pads and fat pads on the soles of his feet similar to those described in Pierpont syndrome., (2008 Wiley-Liss, Inc.)

Published
2008
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90. Measles outbreak in Dublin, 2000.

Author

McBrien J, Murphy J, Gill D, Cronin M, O'Donovan C, and Cafferkey MT

Subjects
Age Distribution, Child, Child, Preschool, Female, Humans, Incidence, Infant, Ireland epidemiology, Male, Measles prevention & control, Measles Vaccine administration & dosage, Prospective Studies, Risk Assessment, Sex Distribution, Survival Rate, Urban Population, Vaccination standards, Vaccination trends, Communicable Disease Control organization & administration, Disease Notification, Disease Outbreaks, Measles epidemiology
Abstract

Background: An outbreak of measles occurred in Ireland between December 1999 and July 2000. The majority of cases were in north Dublin, the catchment area of The Children's University Hospital (TCUH)., Methods: Details of all of the 111 children attending the hospital with a diagnosis of measles between December 1999 and July 2000 were prospectively entered into a database. Charts were subsequently reviewed to extract epidemiologic and clinical details. National figures were obtained from the National Disease Surveillance Centre., Results: In the study period 355 attended TCUH with a serologic or clinical diagnosis of measles, and 111 were admitted (47% female, 53% male). The main indications for admission were dehydration in 79%, pneumonia or pneumonitis in 47% and tracheitis in 32%. Thirteen children (11.7% of those admitted) required treatment in the intensive care unit, and in 7 of these mechanical ventilation was necessary. There were 3 deaths as a result of measles. Public health measures to curb spread of the disease included promotion of immunization for susceptible children nationally and recommending administration of measles-mumps-rubella vaccine (MMR) from the age of 6 months, in North Dublin., Conclusion: This outbreak of measles posed a major challenge to the hospital and the community for the first half of 2000. The national MMR immunization rate before the outbreak was gravely suboptimal at 79%, whereas the rate in North Dublin, the catchment area of TCUH, was <70%. Three children died as a result of a vaccine-preventable illness.

Published
2003
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