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5. Selected abstracts

Author

Corkery, P. P., Leek, B. F., Caulfield, B., Garrett, M., Gormley, J. P., OʼDonnell, 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., OʼConnor, W. T., OʼHara, 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., OʼHare, T., MacDermott, M., Lynch, F., OʼRegan, 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., OʼConnor, J. J., Quinn, A., McHale, J., Moriarty, D., OʼConnor, 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., OʼBrien, 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., OʼHerlihy, C., Keane, D., OʼLeary, 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., OʼLeary, M., Astbury, K., Harmon, D., Sharkey, A., Gaffney, G., OʼRegan, 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., OʼDonoghue, 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., OʼRiordan, M., OʼGorman, C., Mongan, C., McCafferkey, M., Henry, G., McKenna, P., OʼMalley, A., Devaney, D., Kelleghan, P., Mooney, E. E., Gillan, J. E., Fitzpatrick, M., McQuillan, K., Heffron, C., Hodnett, P., Curtain, A., OʼConnor, T. C. F., Connell, T. G., Waldron, D., Gorman, W., Bolger, T., OʼKeefe, M., Murphy, J., Dolan, L. M., Traub, A. I., Slattery, M. M., 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., OʼFlanagan, 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., OʼReilly, D., OʼConnell, 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., OʼDonnell, 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., OʼConnell, V., Evans, D. S., Mhuircheartaigh, Ni J., OʼDonnell, 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., OʼConnell, J., Molloy, M. G., Shanahan, F., Guerin, J., Casey, E., Feighery, C., Lin, F., Jackson, J., Pendleton, A., Wright, G. D., Hughes, A. E., OʼGradaigh, D., Debham, I., Compston, J., McEvoy, A., Murphy, E. P., Salonen, D., Payne, P., Lax, M., Lapp, V., Inman, R., OʼRourke, K., Brennan, D., Harty, J., McCarthy, C., OʼByrne, 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., Casey, E. B., OʼLeary, A., Breen, D., Tuite, D., McInerney, D., Sim, R., Frederic, A. L., Smith, O., White, B., Murphy, M., Silke, C., OʼKeeffe, 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., OʼLeary, J., da Silva, I., Bermingham, N., Gogarty, M., Gallagher, L. P., OʼHara, 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., OʼLorcain, P., Comber, H., Evans, A., Jones, J., Garavan, C., Kelleher, K., Boland, M. C., Healy, R., OʼSullivan, 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., OʼLoan, 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., OʼHalloran, D., OʼNeill, 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., Rahman, Norashikin N., Sheehan, J., Wall, C., Kelleher, B., OʼBroin, 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., OʼMeara, 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., OʼBrien, 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., OʼCeallaigh, C., McGlynn, H., Bergin, E., 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., OʼBroin, 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., OʼNeill, D., Counihan, A., Hickey, D., Keogan, M. T., Harvey, K., OʼRiordan, E., Waldek, S., Kalra, P. A., OʼDonoghue, D. J., Foley, R. N., Kelliher, D., Mellotte, G., Giblin, L., Keogh, J. A. B., OʼConnell, M., OʼMeara, A., Breatnach, F., Gillick, J., Tazawa, H., Puri, P., Molloy, E., OʼNeill, A. J., Sheridan-Pereira, M., Fitzpatrick, J. M., Webb, D. W., Watson, R. W. G., Linnane, B., OʼDonnell, C., Clarke, T. A., Martin, C., McKay, M., McBrien, J., Glynn, F., OʼDonovan, 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., Walsh, K., Duff, D., Slizlok, P. O., Halahakoon, 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., OʼGrady, P., Barry, O., Stewart, M. C., Alderdice, F., Matthews, T. G., McDonnell, M., McGarvey, C., OʼRegan, M., Chróinín, Ní M., Tormey, P., Ennis, S., Green, A. J., Abbas, S., OʼMarcaigh, 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., OʼConnell, L., Mcdonagh, B., Awan, A., Gill, D., Kakkar, R., Warner, J. A., OʼConnor, 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., OʼConnell, 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., OʼNeill, M., OʼRiordan, S., Basheer, S. M. B., OʼCallaghan, 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., OʼMahony, O., Keegan, M., Ward, K., Barton, D., Poulton, J., Treacy, E., Honour, J., deCaluwe, D., Chróinín, Ni 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., OʼBrien, 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., 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., OʼConnor, C. M., Nichelson, A., Lynch, N. E., Finch, D., Foley, M., Scallan, E., Dillon, B., Lyons, S., OʼLoughlin, R., Ward, M., Nally, R., Harkin, A., Kelly, J. P., Leonard, B. E., Magee, P., Connor, T. J., Shen, Y., McCullough, G. R., McDonough, S. M., Niocaill, Nic 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., OʼKeeffe, 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., OʼCuinn, G., Snow, H. M., OʼRegan, D., Markos, H. F., Pollock, K., Cannon, D. M., McBean, G., OʼRiordan, A., Quinlan, L. R., Kane, M. T., Higglns, B. D., Moriarty, D. M., Fitzgerald, D., Katkada, A., Canny, G., MacMathuna, P., OʼDonoghue, D., OʼDonovan, M. M., Schuur, A. G., Murphy, K. J., Foley, A. G., ten Bruggencate, S. J. M., and Ireland, L.

Published
2000
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6. Blockade of MIF-CD74 signalling on macrophages and dendritic cells restores the anti-tumour immune response against metastatic melanoma

Author

Figueiredo, C, Azevedo, R, Mousdell, S, Resende-Lara, P, Ireland, L, Santos, A, Girola, N, Cunha, R, Schmid, MC, Polonelli, L, Travassos, L, and Mielgo Iza, A

Subjects
chemical and pharmacologic phenomena
Abstract

Mounting an effective immune response against cancer requires the activation of innate and adaptive immune cells. Metastatic melanoma is the most aggressive form of skin cancer. While immunotherapies have shown a remarkable success in melanoma treatment, patients develop resistance by mechanisms that include the establishment of an immune suppressive tumor microenvironment. Thus, understanding how metastatic melanoma cells suppress the immune system is vital to develop effective immunotherapies against this disease. In this study, we find that macrophages (MOs) and dendritic cells (DCs) are suppressed in metastatic melanoma and that the Ig-CDR-based peptide C36L1 is able to restore MOs and DCs’ antitumorigenic and immunogenic functions and to inhibit metastatic growth in lungs. Specifically, C36L1 treatment is able to repolarize M2-like immunosuppressive MOs into M1-like antitumorigenic MOs, and increase the number of immunogenic DCs, and activated cytotoxic T cells, while reducing the number of regulatory T cells and monocytic myeloid-derived suppressor cells in metastatic lungs. Mechanistically, we find that C36L1 directly binds to the MIF receptor CD74 which is expressed on MOs and DCs, disturbing CD74 structural dynamics and inhibiting MIF signaling on these cells. Interfering with MIF–CD74 signaling on MOs and DCs leads to a decrease in the expression of immunosuppressive factors from MOs and an increase in the capacity of DCs to activate cytotoxic T cells. Our findings suggest that interfering with MIF–CD74 immunosuppressive signaling in MOs and DCs, using peptide-based immunotherapy can restore the antitumor immune response in metastatic melanoma. Our study provides the rationale for further development of peptide-based therapies to restore the antitumor immune response in metastatic melanoma.

Published
2018

7. Rigorous 3D change determination in Antarctic Peninsula glaciers from stereo WorldView-2 and archival aerial imagery

Author

Fieber, K, Mills, JP, Miller, PE, Clarke, Lucy E, Ireland, L, and Fox, AJ

Subjects
GB, GE, G1
Abstract

This paper presents detailed elevation and volume analysis of 16 individual glaciers, grouped at four locations, spread across the Antarctic Peninsula (AP). The study makes use of newly available WorldView-2 satellite stereo imagery to exploit the previously untapped value of archival stereo aerial photography. High resolution photogrammetric digital elevation models (DEMs) are derived to determine three-dimensional glacier change over an unprecedented time span of six decades with an unparalleled mean areal coverage of 82 % per glacier. The use of an in-house robust surface matching algorithm ensured rigorous alignment of the DEMs to overcome inherent problems associated with processing archival photography, most notably the identification and correction of scale error in some datasets. The analysis provides insight into one of the most challenging and data scarce areas on the planet by expanding the spatial extent north of the AP to include previously unstudied glaciers located in the South Shetland Islands. 81 % of glaciers studied showed considerable loss of volume over the period of record. The mean annual mass loss for all glaciers yielded 0.24 ±0.08 m.w.e. per year, with a maximum mass loss of up to 62 m.w.e. and frontal retreat exceeding 2.2 km for Stadium Glacier, located furthest north on Elephant Island. Observed volumetric loss was broadly, though not always, correlated with frontal retreat. The combined mass balance of all 16 glaciers yielded -1.862 ± 0.006 Gt, which corresponds to -0.005 26 mm sea level equivalent (SLE) over the 57 year observation period.

Published
2018

8. Alcohol Use, Alcohol-related Aggression and Intimate Partner Abuse: A Cross-sectional Survey of Convicted Versus General Population Men in Scotland

Author

Gilchrist, Elizabeth, Ireland, L., Forsyth, A., Godwin, J., and Laxton, T.

Subjects
BF
Abstract

Introduction and Aims. Scotland has a particular problem with alcohol, and the links between intimate partner abuse (IPA)\ud and alcohol appear stronger here than elsewhere across Europe. This study explored differences in alcohol use, related aggression and\ud relationship conflict across a number of groups: men convicted for intimate partner abuse, men convicted of general offences and men\ud recruited from community sports teams. Design and Methods. Participants (n = 64) completed three questionnaires exploring\ud their experiences of alcohol use (Alcohol Use Disorders Identification Test, AUDIT); alcohol and aggression (Alcohol Related\ud Aggression Questionnaire, ARAQ-28), and relationship conflict (Revised Conflict Tactics Scale, CTS-2). Results. There were\ud significant differences across the groups in terms of AUDIT and ARAQ-28 scores, IPA and general offenders scored higher than\ud the community sample. CTS-2 scores showed significant differences: both offender groups reported more use of negotiation and\ud psychological abuse, than the community men, and IPA offenders reported causing more physical harm than either general offenders\ud or the community sample. ARAQ-28 scores correlated with psychological abuse for general offenders. Alcohol use was\ud very high across all groups, but the community group did not endorse an aggression-precipitating view of alcohol and did not\ud report high IPA. Discussion and Conclusions. Discussed is the need for cross-cultural research to explore putative mediators\ud and moderators in the relationship between alcohol, aggressiveness and IPA. [Gilchrist EA, Ireland L, Forsyth A, Godwin J,\ud Laxton T. Alcohol use, alcohol-related aggression and intimate partner abuse: A cross-sectional survey of convicted\ud versus general population men in Scotland. Drug Alcohol Rev 2017;36:20-23]

Published
2017

12. G325(P) Understanding uptake of immunisations in travelling and gypsy communities

Author

Bedford, H, primary, Beach, H, additional, Cheater, F, additional, Condon, L, additional, Crocker, A, additional, Dyson, L, additional, Emslie, C, additional, Kerr, S, additional, Kemsley, P, additional, Ireland, L, additional, Lewis, H, additional, Mytton, J, additional, Overend, K, additional, Redsell, S, additional, Richardson, Z, additional, Shepherd, C, additional, Smith, L, additional, and Jackson, C, additional

Published
2016
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14. Purification from rat liver of a novel constitutively expressed member of the aldo-keto reductase 7 family that is widely distributed in extrahepatic tissues

Author

Kelly, V P, Ireland, L S, Ellis, E M, and Hayes, J D

Subjects
Male, Blotting, Western, Molecular Sequence Data, Chromatography, Affinity, Cytosol, Liver Neoplasms, Experimental, Aldehyde Reductase, Tumor Cells, Cultured, Animals, Humans, Amino Acid Sequence, Cloning, Molecular, Sequence Homology, Amino Acid, Reverse Transcriptase Polymerase Chain Reaction, Chromatography, Ion Exchange, Peptide Fragments, Rats, Inbred F344, Recombinant Proteins, Rats, Isoenzymes, Kinetics, Liver, Organ Specificity, Chromatography, Gel, Female, Sequence Alignment, Research Article
Abstract

Antiserum raised against human aflatoxin B(1) aldehyde reductase 1 (hAFAR1) has been used to identify a previously unrecognized rat aldo-keto reductase (AKR). This novel enzyme is designated rat aflatoxin B(1) aldehyde reductase 2 (rAFAR2) and it characteristically migrates faster during SDS/PAGE than does the archetypal ethoxyquin-inducible rAFAR protein (now called rAFAR1). Significantly, rAFAR2 is essentially unreactive with polyclonal antibodies raised against rAFAR1. Besides its distinct electrophoretic and immunochemical properties, rAFAR2 appears to be regulated differently from rAFAR1 as it is expressed in most rat tissues and does not appear to be induced by ethoxyquin. Multiple forms of rAFAR2 have been identified. Anion-exchange chromatography on Q-Sepharose, followed by adsorption chromatography on columns of Matrex Orange A and Cibacron Blue, have been employed to purify rAFAR2 from rat liver cytosol. The Q-Sepharose chromatography step resulted in the resolution of rAFAR2 into three peaks of AKR activity, two of which were purified and shown to be capable of catalysing the reduction of 2-carboxybenzaldehyde, succinic semialdehyde, 4-nitrobenzaldehyde and 9,10-phenathrenequinone. The two most highly purified rAFAR2-containing preparations eluted from the Cibacron Blue column were 91 and 98% homogeneous. Analysis of these by SDS/PAGE indicated that the least anionic (peak CBA5) comprised a polypeptide of 37.0 kDa, whereas the most anionic (peak CBA6) contained two closely migrating polypeptides of 36.8 and 37.0 kDa; by contrast, in the present study, rAFAR1 was estimated by SDS/PAGE to be composed of 38.0 kDa subunits. Final purification of the 37 kDa polypeptide in CBA5 and CBA6 was accomplished by reversed-phase HPLC. Partial proteolysis of the two preparations of the 37 kDa polypeptide with Staphylococcus aureus V8 protease yielded fragments of identical size, suggesting that they represent the product of a single gene. Furthermore, the peptide maps from CBA5 and CBA6 differed substantially from that yielded by rAFAR1, indicating that they are genetically distinct from the inducible reductase. A peptide generated by CNBr digestion of the 37 kDa polypeptide from CBA6 was shown by Edman degradation to share 88% sequence identity with residues Tyr(168)-Leu(183) of rAFAR1. This provides evidence that the rat protein identified by its cross-reactivity with anti-hAFAR1 serum is an additional member of the AKR7 family.

Published
2000

15. Major differences exist in the function and tissue-specific expression of human aflatoxin B1 aldehyde reductase and the principal human aldo-keto reductase AKR1 family members

Author

O'connor, T, Ireland, L S, Harrison, D J, and Hayes, J D

Subjects
Recombinant Fusion Proteins, Blotting, Western, Molecular Sequence Data, Drug Resistance, Kidney, Immunohistochemistry, Catalysis, Substrate Specificity, Isoenzymes, Molecular Weight, Alcohol Oxidoreductases, Kinetics, Liver, Aldehyde Reductase, Organ Specificity, Escherichia coli, Humans, Thermodynamics, Cloning, Molecular, Research Article
Abstract

Complementary DNA clones encoding human aflatoxin B(1) aldehyde reductase (AKR7A2), aldehyde reductase (AKR1A1), aldose reductase (AKR1B1), dihydrodiol dehydrogenase 1 (AKR1C1) and chlordecone reductase (AKR1C4) have been expressed in Escherichia coli. These members of the aldo-keto reductase (AKR) superfamily have been purified from E. coli as recombinant proteins. The recently identified AKR7A2 was shown to differ from the AKR1 isoenzymes in being able to catalyse the reduction of 2-carboxybenzaldehyde. Also, AKR7A2 was found to exhibit a narrow substrate specificity, with activity being restricted to succinic semialdehyde (SSA), 2-nitrobenzaldehyde, pyridine-2-aldehyde, isatin, 1,2-naphthoquinone (1,2-NQ) and 9,10-phenanthrenequinone. In contrast, AKR1A1 reduces a broad spectrum of carbonyl-containing compounds, displaying highest specific activity for SSA, 4-carboxybenzaldehyde, 4-nitrobenzaldehyde, pyridine-3-aldehyde, pyridine-4-aldehyde, 4-hydroxynonenal, phenylglyoxal, methylglyoxal, 2,3-hexanedione, 1, 2-NQ, 16-ketoestrone and d-glucuronic acid. Comparison between the kinetic properties of AKR7A2 and AKR1A1 showed that both recombinant enzymes exhibited roughly similar k(cat)/K(m) values for SSA, 1,2-NQ and 16-ketoestrone. Many of the compounds which are substrates for AKR1A1 also serve as substrates for AKR1B1, though the latter enzyme was shown to display a specific activity significantly less than that of AKR1A1 for most of the aromatic and aliphatic aldehydes studied. Neither AKR1C1 nor AKR1C4 was found to possess high reductase activity towards aliphatic aldehydes, aromatic aldehydes, aldoses or dicarbonyls. However, unlike AKR1A1 and AKR1B1, both AKR1C1 and AKR1C4 were able to catalyse the oxidation of 1-acenaphthenol and, in addition, AKR1C4 could oxidize di- and tri-hydroxylated bile acids. Specific antibodies raised against AKR7A2, AKR1A1, AKR1B1, AKR1C1 and AKR1C4 have been used to show the presence of all of the reductases in human hepatic cytosol; the levels of AKR1B1 and AKR1C1 were markedly elevated in livers with alcohol-associated injury, and indeed AKR1B1 was only detectable in livers with evidence of alcoholic liver disease. Western blotting of extracts from brain, heart, kidney, liver, lung, prostate, skeletal muscle, small intestine, spleen and testis showed that AKR7A2 is present in all of the organs examined, and AKR1B1 is similarly widely distributed in human tissues. These experiments revealed however, that the expression of AKR1A1 is restricted primarily to brain, kidney, liver and small intestine. The AKR1C family members proved not to be as widely expressed as the other reductases, with AKR1C1 being observed in only kidney, liver and testis, and AKR1C4 being found in liver alone. As human kidney is a rich source of AKR, the isoenzymes in this organ have been studied further. Anion-exchange chromatography of human renal cytosol on Q-Sepharose allowed resolution of AKR1A1, AKR1B1, AKR1C1 and AKR7A2, as identified by substrate specificity and Western blotting. Immunohistochemistry of human kidney demonstrated that AKR7A2 is expressed in a similar fashion to the AKR1 family members in proximal and distal convoluted renal tubules. Furthermore, both AKR7A2 and AKR1 members were expressed in renal carcinoma cells, suggesting that these groups of isoenzymes may be engaged in related physiological functions.

Published
1999

16. M19 Differences in patient and physician viewpoints of the management of idiopathic pulmonary fibrosis (ipf)

Author

Maher, TM, Swigris, JJ, Kreuter, M, Wijsenbeek, M, Axmann, J, Ireland, L, and Nathan, SD

Abstract

IntroductionA majority of patients with IPF do not receive antifibrotic therapy with pirfenidone or nintedanib. We investigated viewpoints about IPF care and treatment amongst patients, and amongst physicians with a ‘watch and wait’ approach (WWP) or a proactive approach (PP).MethodsParticipants from Europe and Canada took part in an online survey. Responses were collected from patients with IPF, and from physicians responsible for initiation of IPF treatment who had consulted with ≥5 patients with IPF within 3 months. A mixture of WWP (monitor for ≥4 months post-diagnosis in ≥50% of patients before initiating antifibrotic) and PP (initiate antifibrotic <4 months post-diagnosis in majority of patients) were recruited.Results43 patients and 254 physicians were surveyed between September and October 2016. Only 56% of patients felt that they received enough information at diagnosis: 58% were advised that IPF is progressive; 44% discussed prognosis; and 49% were told about treatment options. Although the majority of patients (93%) preferred to receive information from their physician, most patients sought additional information about IPF (86%), treatment (81%), and/or prognosis (76%). Most patients (86%) felt that the ability of antifibrotic treatments to slow IPF progression was more important than side-effect profiles. Overall, 86% of patients who had received antifibrotic therapy felt confident in managing side effects. WWP were less likely to discuss IPF prognosis than PP, even when asked specifically by patients (Table). 62% and 38% of patients with ‘mild’ IPF were treated with an antifibrotic <4 months post-diagnosis by PP and WWP, respectively. WWP were more concerned about treatment side effects than PP (28% vs 17%, respectively); PP were more concerned about disease progression than WWP (83% vs 72%, respectively).ConclusionsWe identified a disparity between the information patients want at diagnosis and the information they receive from physicians. Furthermore, Results suggest that PP may be more confident with the benefit-risk profile of antifibrotic treatment than WWP. A belief in effective treatment options may aid conversation with patients regarding their IPF diagnosis, thereby enabling patients to make informed treatment decisions.Abstract M19 Table 1Differences between physicians regarding disease prognosis and treatment decisionsWWPn=118PPn=136Mention typical IPF prognosis at diagnosis 47% 59% Will avoid discussing typical prognosis/life expectancy even when patient asks 51% 33%* Comfortable discussing IPF prognosis 21% 34%* Strongly believe they can make a big difference in IPF patients’ lives post-diagnosis 29% 45%* Agree that antifibrotic therapies significantly slow the progression of IPF 36% 51%* Reasons for not treating patients with ‘mild’ IPF with an antifibrotic: Patient is asymptomatic/has few symptoms66% 36%* Patient has stable disease 65% 33%* Patient has good lung function 58% 38%* Patient has a good quality of life 53% 27%* Patient has IPF that is progressing slowly 53% 26%* *p<0.05 for PP vs WWP.

Published
2017
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17. 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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22. Building the future: children's views on nurses and hospital care.

Author

Fletcher T, Glasper A, Prudhoe G, Battrick C, Coles L, Weaver K, and Ireland L

Abstract

Healthcare policies such as standard 7 of the National Service Framework for Children, Young People and Maternity Services and the new NMC standards for pre-registration nursing programmes emphasise the need for universities and their partner trusts to engage with patients and the public in developing both nurse training courses and services. This article describes a two-arm study into the views and experiences of children with regard to hospitals. Conducted as part of an ongoing commitment to the reconfiguration of children's services and the development of a new undergraduate children's nursing programme, the study collected data from 61 children in two children's hospitals in the south of England and from eight members of a city youth parliament. Aims: The study sought to involve child users in service planning through two objectives: 1) to ascertain the views of children and young people on what skills, knowledge and attitudes, children's nurses of the future will need to care for sick children and their families; and 2) to seek the views of young people on what children think about before being admitted to hospital, and subsequently as inpatients. Method: The study used a draw and write/tell technique. The main outcome measures were description and analysis of those attributes which children believe nurses of the future should possess, and of those factors which inhibit or enhance childhood hospital admission. Results: A number of themes emerged from analysis of the data: notably that children's nurses of the future should be skilled in both verbal and non-verbal communication, as well as having fundamental clinical skills. Issues relating to children about to be admitted to hospital included being scared or worried, and fear of the unknown, while concerns after admission to hospital related to the care environment, social needs, and individual/personal needs and requirements. Conclusions: This patient and public involvement study revealed a number areas that children and young people believe to be important for the future training of children's nurses. Additionally, the factors which children consider inhibit or enhance the experience of hospital admission have been identified. [ABSTRACT FROM AUTHOR]

Published
2011
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24. Synthesis and Structure−Activity Studies on N-[5-(1H-Imidazol-4-yl)-5,6,7,8-tetrahydro-1-naphthalenyl]methanesulfonamide, an Imidazole-Containing α<INF>1A</INF>-Adrenoceptor Agonist<SUP>1</SUP>

Author

Altenbach, R. J., Khilevich, A., Kolasa, T., Rohde, J. J., Bhatia, P. A., Patel, M. V., Searle, X. B., Yang, F., Bunnelle, W. H., Tietje, K., Bayburt, E. K., Carroll, W. A., Meyer, M. D., Henry, R., Buckner, S. A., Kuk, J., Daza, A. V., Milicic, I. V., Cain, J. C., Kang, C. H., Ireland, L. M., Carr, T. L., Miller, T. R., Hancock, A. A., Nakane, M., Esbenshade, T. A., Brune, M. E., O'Neill, A. B., Gauvin, D. M., Katwala, S. P., Holladay, M. W., Brioni, J. D., and Sullivan, J. P.

Abstract

Structure−activity studies were performed on the α1A-adrenoceptor (AR) selective agonist N-[5-(1H-imidazol-4-yl)-5,6,7,8-tetrahydro-1-naphthalenyl]methanesulfonamide (4). Compounds were evaluated for binding activity at the α1A, α1b, α1d, α2a, and α2B subtypes. Functional activity in tissues containing the α1A (rabbit urethra), α1B (rat spleen), α1D (rat aorta), and α2A (rat prostatic vas deferens) was also evaluated. A dog in vivo model simultaneously measuring intraurethral pressure (IUP) and mean arterial pressure (MAP) was used to assess the uroselectivity of the compounds. Many of the compounds that were highly selective in vitro for the α1A-AR subtype were also more uroselective in vivo for increasing IUP over MAP than the nonselective α1-agonists phenylpropanolamine (PPA) (1) and ST-1059 (2, the active metabolite of midodrine), supporting the hypothesis that greater α1A selectivity would reduce cardiovascular side effects. However, the data also support a prominent role of the α1A-AR subtype in the control of MAP.

Published
2004

26. Actions of A-131701, a novel, selective antagonist for alpha-1A compared with alpha-1B adrenoceptors on intraurethral and blood pressure responses in conscious dogs and a pharmacodynamic assessment of in vivo prostatic selectivity.

Author

A, Hancock A, E, Brune M, G, Witte D, C, Marsh K, S, Katwala, I, Milicic, M, Ireland L, D, Crowell, D, Meyer M, and F, Kerwin J

Abstract

A-131701 (3-[2-((3aR,9bR)-cis-6-methoxy-2,3,3a,4,5,9b, hexahydro-[1H]-benz[e]isoindol-2-yl)ethyl]pyrido [3',4': 4,5]thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione) is a novel compound previously shown to be selective for alpha-1a sites compared with alpha-1b adrenoceptors in radioligand binding studies and isolated tissue bioassays and to block canine urethral pressure (IUP) responses to exogenous alpha-1 adrenergic agonists to a greater extent than blood pressure responses. In conscious dogs in which IUP and mean arterial blood pressure (MABP) responses were measured periodically up to 24 hr, A-131701 blocked phenylephrine (PHE)-induced increases in IUP to a greater extent than MABP responses, and the blockade of the IUP effects of PHE was significantly different from control for up to 12 hr after doses greater than 0.3 mg/kg p.o., whereas blood pressure effects were of a lesser extent and duration. In addition to the weak antagonism of PHE-induced blood pressure responses, A-131701 also exhibited minimal effects on basal blood pressure in the dog, unlike terazosin, doxazosin or tamsulosin. Pharmacokinetic analysis of plasma samples from dogs indicated that A-131701 had a half-life of 0.4 to 0.8 hr and a bioavailability of 30 to 50% in dogs. Somewhat longer half-lives were observed in rat and monkey, with bioavailability values in the 25 to 30% range. Evidence of nonlinearity of pharmacokinetics was obtained in dogs and monkeys. Pharmacodynamic analysis revealed differences between A-131701 and nonselective alpha-1 adrenoceptor antagonists in selectivity for prostatic versus vascular alpha-1 adrenoceptors based on either extent or duration of blockade, which were either similar to or superior to compounds such as tamsulosin or REC 15/2739. These data demonstrate that A-131701 selectively blocks canine prostatic alpha-1 adrenoceptors for prolonged periods compared with MABP responses in vivo. Therefore, A-131701 should have clinical utility in the pharmacotherapy of benign prostatic hyperplasia.

Published
1998

28. Differential effects of 2,4-dithiobiuret on the synthesis and release of acetylcholine and dopamine from rat pheochromocytoma (PC12) cells.

Author

Ireland, L M, Yan, C H, Nelson, L M, and Atchison, W D

Abstract

Chronic administration of 2,4-dithiobiuret (DTB), causes delayed-onset neuromuscular weakness in rats. This effect results from inhibition of quantal release of acetylcholine (ACh) from motor nerve terminals. The effects of noncholinergic neurotransmission are unknown. The purpose of the present study was to examine the presynaptic mechanisms involved in DTB-induced inhibition of ACh release, particularly, the specificity of action of DTB for cholinergic secretion. Differentiated pheochromocytoma (PC12) cells were used to compare the effects of DTB on the content and release of ACh and dopamine (DA) using neurochemical techniques. At concentrations of 50 to 1000 microM, DTB had little or no effect on [3H]choline uptake or on the spontaneous release of endogenous or [3H]ACh, but caused a significant decrease in release of endogenous or [3H]ACh elicited by depolarization with elevated extracellular [K+]. DTB reduced evoked release of ACh without altering cellular levels of ACh or choline, suggesting that DTB acts directly on mechanisms involved in ACh release. These alterations occurred without prominent alterations in [Ca2+]i as measured by fluorescence microscopy of individual PC12 cells loaded with fura-2. Moreover, DTB did not affect the increase of [Ca2+]i of PC12 cells in response to KCl-induced depolarization. alpha-Latrotoxin-stimulated release of ACh was not inhibited by DTB. DTB-induced suppression of depolarization-evoked release of [3H]ACh was associated with an increased level of [3H]ACh in the vesicular pool although the cytosolic pool was unaffected. High concentrations of DTB also reduced depolarization-evoked release of DA and inhibited DA synthesis resulting in a decrease in the readily releasable pool of DA. These effects occurred at higher concentrations and after longer exposures to DTB than were necessary to alter ACh release. Inasmuch as DA synthesis in the PC12 cell has been shown to be modulated by ACh release, this effect on DA release may reflect a consequence of the diminished release of ACh. These results suggest that DTB alters the release of ACh by interrupting either the mobilization and/or release of the vesicular pool of ACh.

Published
1995

30. Radar Investigations of the Bat Hazard to High Performance Aircraft at Randolph AFB, Texas

Author

AIR FORCE WEAPONS LAB KIRTLAND AFB N MEX, Ireland,L. C., Harris,V. A., Ireland,S. S., Williams,T. C., Williams,J. M., AIR FORCE WEAPONS LAB KIRTLAND AFB N MEX, Ireland,L. C., Harris,V. A., Ireland,S. S., Williams,T. C., and Williams,J. M.

Abstract

During the months of April through October, Mexican free-tailed bats (Tadarida brasiliensis mexicana) are a major cause of T-38 engines failures at Randolph AFB, Texas. The airborne behavior of T.b mexicana emerging from and returning to the Bracken cave, near Randolph AFB, was observed with both search and height-finding radars. Radar echoes from dense groups of bats covered areas as large as 500 sq km and rose to altitudes of over 3,000 m. Evening bat flights appeared to have three distinct phases of development; exit from the roost and ascent, transistion to level flght, and dispersal. In the dispersal phase, the bats usually traveled directly toward Randolph AFB. Bat flights may be grouped into three types on the basis of their vertical distribution. One type, characterized by flight at low altitude, was usually observed on nights when T-38s were damaged. A bat avoidance program, based on real time radar observations, was initiated at Randolph AFB during the summer of 1971 and continued thru 1974. Since the start of the program, the frequency of strikes has decreased. It appears possible to predict nights when bat strikes are most likely to occur 24 hours in advance. Strobe lights were found to be an ineffective bat deterrent.

Published
1976

31. A Risk Management Model for the Defense System Acquisition Process

Author

SWL INC MCLEAN VA, Ireland,L. R., SWL INC MCLEAN VA, and Ireland,L. R.

Abstract

This paper presents a risk management model that is designed to identify, assess, and manage risk for Defense weapon system acquisitions. The model provides a detailed, disciplined process that establishes baseline definitions, principles for risk management, and diagrams which support the risk management process. (Author), This article is from 'Management of Risk and Uncertainty in Systems Acquisition: Proceedings of the 1983 Defense Risk and Uncertainty Workshop Held at Fort Belvoir, Virginia on 13-15 July 1983,' AD-A136 230, p192-199.

Published
1983

32. Aflatoxin aldehyde reductases

Author

Vincent Kelly, O Connor, T., Ellis, E. M., Ireland, L. S., Slattery, C. M., Sherratt, P. J., Crouch, D. H., Cavin, C., Schilter, B., Gallina, A., and Hayes, J. D.

43. In the moment.

Author

Regan P and Ireland L

Abstract

A health visitor and a midwife describe their experiences of working in an exemplar interprofessional service model in Warrington. [ABSTRACT FROM AUTHOR]

Published
2009

45. Overcoming Osimertinib Resistance with AKT Inhibition in EGFRm-Driven Non-Small Cell Lung Cancer with PIK3CA/PTEN Alterations.

Author

Grazini U, Markovets A, Ireland L, O'Neill D, Phillips B, Xu M, Pfeifer M, Vaclova T, Martin MJ, Bigot L, Friboulet L, Hartmaier R, Cuomo ME, Barry ST, Smith PD, and Floc'h N

Subjects
Humans, Animals, Mice, Cell Line, Tumor, Protein Kinase Inhibitors therapeutic use, Protein Kinase Inhibitors pharmacology, Pyrimidines therapeutic use, Pyrimidines pharmacology, Pyrimidines administration & dosage, Indoles, Pyrroles, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, PTEN Phosphohydrolase genetics, Class I Phosphatidylinositol 3-Kinases genetics, Class I Phosphatidylinositol 3-Kinases antagonists & inhibitors, Acrylamides pharmacology, Acrylamides therapeutic use, Aniline Compounds pharmacology, Aniline Compounds therapeutic use, Aniline Compounds administration & dosage, Drug Resistance, Neoplasm genetics, Drug Resistance, Neoplasm drug effects, Proto-Oncogene Proteins c-akt metabolism, ErbB Receptors antagonists & inhibitors, ErbB Receptors genetics, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms pathology, Mutation, Xenograft Model Antitumor Assays
Abstract

Purpose: Osimertinib is an EGFR tyrosine kinase inhibitor indicated for the treatment of EGFR-mutated (EGFRm)-driven lung adenocarcinomas. Osimertinib significantly improves progression-free survival in first-line-treated patients with EGFRm advanced non-small cell lung cancer (NSCLC). Despite the durable disease control, the majority of patients receiving osimertinib eventually develop disease progression., Experimental Design: ctDNA profiling analysis of on-progression plasma samples from patients treated with osimertinib in both first- (phase III, FLAURA trial) and second-line trials (phase III, AURA3 trial) revealed a high prevalence of PIK3CA/AKT/PTEN alterations. In vitro and in vivo evidence using CRISPR-engineered NSCLC cell lines and patient-derived xenograft (PDX) models supports a functional role for PIK3CA and PTEN mutations in the development of osimertinib resistance., Results: These alterations are functionally relevant as EGFRm NSCLC cells with engineered PIK3CA/AKT/PTEN alterations develop resistance to osimertinib and can be resensitized by treatment with the combination of osimertinib and the AKT inhibitor capivasertib. Moreover, xenograft and PDX in vivo models with PIK3CA/AKT/PTEN alterations display limited sensitivity to osimertinib relative to models without alterations, and in these double-mutant models, capivasertib and osimertinib combination elicits an improved antitumor effect versus osimertinib alone., Conclusions: Together, this approach offers a potential treatment strategy for patients with EGFRm-driven NSCLC who have a suboptimal response or develop resistance to osimertinib through PIK3CA/AKT/PTEN alterations. See related commentary by Vokes et al., p. 3968., (©2024 American Association for Cancer Research.)

Published
2024
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46. Sexually transmitted and blood-borne infections by sex, methamphetamine use, and houselessness before, at, and after HIV diagnosis in Manitoba, Canada.

Author

Sorokopud-Jones M, Sharp A, Haworth-Brockman M, Kasper K, MacKenzie L, Ireland L, Gawlik K, Lopez L, Vanegas JM, Bullard J, Boodman C, Sanguins J, Payne M, Templeton K, Keynan Y, and Rueda ZV

Abstract

Objectives: Describe the proportion of people newly living with HIV with sexually transmitted and blood-borne infections (STBBIs) before, at, and after HIV diagnosis in Manitoba, Canada., Methods: A retrospective cohort study reviewed clinical charts of all 404 people ≥18 years old newly diagnosed with HIV in Manitoba, Canada between 2018 and 2021. Syphilis, hepatitis C and B, gonorrhea, and chlamydia infections before, at, and after HIV diagnosis were recorded and analyzed by sex at birth, injection drug use status, use of methamphetamines, and housing status., Results: A total of 53% of people were diagnosed with syphilis, 44.1% with gonorrhea, 42.8% with chlamydia, and 40.6% with hepatitis C at least once. Among females, 64.1% had at least one or more STBBIs diagnoses before HIV diagnosis compared with 44.8% of males. Over 70% of people experiencing houselessness had at least one STBBI diagnosis before their HIV diagnosis compared with 43.9% of people not houseless. Among people who used methamphetamines, 68.3% had one or more STBBIs before HIV diagnosis compared with 28.9% of people who do not use methamphetamines. In a multivariable analysis houselessness, methamphetamine use, and younger age were associated with increased risk of any STBBIs., Conclusions: In our Manitoba cohort of people living with HIV, disproportionately more females, people experiencing houselessness, and those who use methamphetamine were diagnosed with STBBIs. The proportion of new infections before HIV diagnoses highlights a missed opportunity to provide prevention modalities, including pre-exposure prophylaxis, and the proportion after HIV diagnosis emphasizes the importance of enhancing engagement, repeated testing, and educational strategies to ameliorate ongoing exposures., Competing Interests: The authors have no competing interests to declare., (© 2024 The Author(s).)

Published
2024
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47. Inhibition of insulin-like growth factors increases production of CXCL9/10 by macrophages and fibroblasts and facilitates CD8 + cytotoxic T cell recruitment to pancreatic tumours.

Author

Freeman P, Bellomo G, Ireland L, Abudula M, Luckett T, Oberst M, Stafferton R, Ghaneh P, Halloran C, Schmid MC, and Mielgo A

Subjects
Humans, Animals, Mice, Somatomedins metabolism, Cell Line, Tumor, T-Lymphocytes, Cytotoxic immunology, STAT1 Transcription Factor metabolism, CD8-Positive T-Lymphocytes immunology, Signal Transduction, Fibroblasts metabolism, Fibroblasts immunology, Insulin-Like Peptides, Chemokine CXCL9 metabolism, Pancreatic Neoplasms immunology, Pancreatic Neoplasms pathology, Pancreatic Neoplasms metabolism, Tumor Microenvironment immunology, Chemokine CXCL10 metabolism, Macrophages immunology, Macrophages metabolism, Carcinoma, Pancreatic Ductal immunology, Carcinoma, Pancreatic Ductal pathology, Carcinoma, Pancreatic Ductal metabolism
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with an urgent unmet clinical need for new therapies. Using a combination of in vitro assays and in vivo preclinical models we demonstrate that therapeutic inhibition of the IGF signalling axis promotes the accumulation of CD8 + cytotoxic T cells within the tumour microenvironment of PDAC tumours. Mechanistically, we show that IGF blockade promotes macrophage and fibroblast production of the chemokines CXCL9 and CXCL10 to facilitate CD8 + T cell recruitment and trafficking towards the PDAC tumour. Exploring this pathway further, we show that IGF inhibition leads to increased STAT1 transcriptional activity, correlating with a downregulation of the AKT/STAT3 signalling axis, in turn promoting Cxcl9 and Cxcl10 gene transcription. Using patient derived tumour explants, we also demonstrate that our findings translate into the human setting. PDAC tumours are frequently described as "immunologically cold", therefore bolstering CD8 + T cell recruitment to PDAC tumours through IGF inhibition may serve to improve the efficacy of immune checkpoint inhibitors which rely on the presence of CD8 + T cells in tumours., Competing Interests: Author MO was employed by AstraZeneca. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Freeman, Bellomo, Ireland, Abudula, Luckett, Oberst, Stafferton, Ghaneh, Halloran, Schmid and Mielgo.)

Published
2024
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48. Sex differences in houselessness, injection drug use, and mental health conditions among people newly diagnosed with HIV in Manitoba, Canada from 2018 to 2021: a retrospective cohort study.

Author

Sharp A, Sorokopud-Jones M, Haworth-Brockman M, Kasper K, MacKenzie L, Ireland L, Gawlik K, Lopez L, Vanegas JM, Bullard J, Boodman C, Sanguins J, Payne M, Templeton K, Keynan Y, and Rueda ZV

Abstract

Background: Manitoba saw the highest number of new HIV diagnoses in the province's history in 2021 and is the only Canadian province not meeting any of the previous UNAIDS 90-90-90 targets. Our goal was to describe sex differences and syndemic conditions within an incident HIV cohort in Manitoba, and the HIV treatment initiation and undetectable viral load outcomes., Methods: This was a retrospective cohort study of all people 18 years and older newly diagnosed with HIV in Manitoba, Canada between January 1st, 2018 and December 31st, 2021. Data was collected as follows: before HIV diagnosis : chlamydia, gonorrhoea, syphilis, and/or hepatitis C antibodies. At the time of HIV diagnosis : age, sex, gender, race/ethnicity, sexual orientation. During follow-up : CD4 counts, viral load, HIV treatment, hospitalizations, and number of visits to HIV care. Main exposures evaluated: methamphetamine use, injection drug use, houselessness, and mental health conditions. Outcomes: started antiretroviral treatment and achieved an undetectable viral load. A descriptive statistical analysis was used., Findings: There were 404 new HIV diagnoses in Manitoba from 2018 to 2021; 44.8% were female, 55.2% male; 76.% self-identified as Indigenous, 13.4% white/European, 4.7% African/black; 86.6% cis-gender; 60.9% heterosexual, 13.4% gay, bisexual and men who have sex with men, and 1.7% lesbian. Injection drug use was reported by 71.8% and 43.5% of females and males respectively. Methamphetamine was the most frequently injected drug (62.4%). Amongst females, 81.8% experienced at least one of the following: houselessness (43.1%), mental health comorbidities (46.4%), and injection drug use (71.8%). Only 64.9% of all individuals had an undetectable viral load (61.1% females and 67.9% males), 56.5% among people experiencing houselessness, 59% among young people (≤29 years), and 60.1% among people who inject drugs., Interpretation: People newly diagnosed with HIV in Manitoba are disproportionately experiencing houselessness, mental illness, and injection drug use (mostly methamphetamine). This pattern is more pronounced for female individuals. These findings highlight the need for syndemic and gender-specific approaches, simultaneously addressing social and health conditions, to treat HIV., Funding: This work was supported by the Canadian Institutes of Health Research, The Manitoba Medical Service Foundation, The James Farley Memorial Fund and the Canada Research Chairs Program., Competing Interests: MHB declares work as a consultant for the Assembly of First Nations and the Canadian Institute for the Advancement of Women. There are no competing interests to report., (© 2024 The Author(s).)

Published
2024
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49. Mesothelin Secretion by Pancreatic Cancer Cells Co-opts Macrophages and Promotes Metastasis.

Author

Luckett T, Abudula M, Ireland L, Glenn M, Bellomo G, Stafferton R, Halloran C, Ghaneh P, Jones R, Schmid MC, and Mielgo A

Subjects
Humans, Mesothelin, Cell Line, Tumor, Macrophages metabolism, Tumor Microenvironment physiology, Pancreatic Neoplasms pathology, Carcinoma, Pancreatic Ductal pathology
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease, yet effective treatments to inhibit PDAC metastasis are lacking. The rich PDAC tumor microenvironment plays a major role in disease progression. Macrophages are the most abundant immune cell population in PDAC tumors and can acquire a range of functions that either hinder or promote tumor growth and metastasis. Here, we identified that mesothelin secretion by pancreatic cancer cells co-opts macrophages to support tumor growth and metastasis of cancer cells to the lungs, liver, and lymph nodes. Mechanistically, secretion of high levels of mesothelin by metastatic cancer cells induced the expression of VEGF alpha (VEGFA) and S100A9 in macrophages. Macrophage-derived VEGFA fed back to cancer cells to support tumor growth, and S100A9 increased neutrophil lung infiltration and formation of neutrophil extracellular traps. These results reveal a role for mesothelin in regulating macrophage functions and interaction with neutrophils to support PDAC metastasis., Significance: Mesothelin secretion by cancer cells supports pancreatic cancer metastasis by inducing macrophage secretion of VEGFA and S100A9 to support cancer cell proliferation and survival, recruit neutrophils, and stimulate neutrophil extracellular trap formation. See related commentary by Alewine, p. 513., (©2024 American Association for Cancer Research.)

Published
2024
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50. Drug transactions and the dark web: Public perceptions of the locational setting of offenders and support for drug policy outcomes.

Author

Ireland L and Jardine E

Subjects
Humans, United States, Public Opinion, Police, Criminal Law, Public Policy, Criminals
Abstract

Background: Both legal and extra-legal factors influence judicial and non-judicial opinions about persons who use drugs. Yet, how the locational setting of drug transactions influences public perceptions of drug control policies remains understudied. In particular, the public's view of drug exchanges on the dark web could directly and indirectly influence drug policy, legal decision making, and spending decisions. The study's aim is to identify whether the location of a drug exchange, specifically the dark web, influences public preferences for drug policy and police resourcing., Methods: A sample (n = 1359) from the United States of America was recruited and participated in a discrete choice experiment. The participants compared and repeatedly chose across five iterations between two drug offender profiles with nine set features, such as the location of drug transactions, all with randomized levels. The resulting sample included a total of 13,590 contest pairs., Results: Averaging over the non-locational attributes, respondents indicated that, compared to the dark web, several locational settings for drug exchange (such as the street corner, social media, and an unknown location) needed fewer police resources and offenders were less deserving of longer punishments. No statistically significant difference was found for opinions about harm to communities, and offenders involved in drug exchanges on university campuses were considered more deserving of a substance abuse treatment program than offenders on the dark web., Conclusion: There appears to be a preference for more punitive criminal justice policies for drug transactions occurring on the dark web relative to some other common settings. Such preferences may indicate a novelty effect driven by negative sentiment surrounding the dark web or a perceived deficit in the police's ability to deal with drug crimes on the dark web. These findings suggest that the public may prefer supply-side policing efforts over demand-side policies, which emphasizes harm reduction., 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. This publication is not affiliated with Chainalysis and the views represented herein are those of respective authors., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Published
2024
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