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2. Tenecteplase versus standard of care for minor ischaemic stroke with proven occlusion (TEMPO-2): a randomised, open label, phase 3 superiority trial

Author

Salluzzi, Marina, Blenkin, Nicole, Dueck, Ashley, Doram, Craig, Zhang, Qiao, Kenney, Carol, Ryckborst, Karla, Bohn, Shelly, Collier, Quentin, Taylor, Frances, Lethebe, B. Cord, Jambula, Anitha, Sage, Kayla, Toussaint, Lana, Save, Supryia, Lee, Jaclyn, Laham, N, Sultan, A.A., Deepak, A., Sitaram, A., Demchuk, Andrew M., Lockey, A., Micielli, A., Wadhwa, A., Arabambi, B., Graham, B., Bogiatzi, Chrysi, Doshi, Darshan, Chakraborty, D., Kim, Diana, Vasquez, D, Singh, D, Tse, Dominic, Harrison, E., Smith, E.E., Teleg, E., Klourfeld, E., Klein, G., Sebastian, I.A., Evans, J, Hegedus, J, Kromm, J, Lin, K, Ignacio, K, Ghavami, Kimia, Ismail, M., Moores, M., Panzini, M.A., Boyko, M., Almekhlafi, M.A., Newcommon, Nancy, Maraj, N., Imoukhuede, O., Volny, O., Stys, Peter, Couillard, Phillipe, Ojha, P., Eswaradass, P., Joundi, Raed, Singh, R., Asuncion, R.M., Muir, R.T., Dey, S., Mansoor, S., Wasyliw, S., Nagendra, S., Hu, Sherry, Althubait, S., Chen, S., Bal, S., Van Gaal, Stephen, Peters, Steven, Ray, Sucharita, Chaturvedi, S., Subramaniam, Suresh, Fu, Vivian, Villaluna, K., Maclean, G., King-Azote, P., Ma, C., Plecash, A., Murphy, C., Gorman, J., Wilson, L., Zhou, L., Benevente, O., Teal, P., Yip, S., Mann, S., Dewar, B., Demetroff, M., Shamloul, R., Beardshaw, R., Roberts, S., Blaquiere, D., Stotts, G., Shamy, M., Bereznyakova, O., Fahed, R., Alesefir, W., Lavoie, Suzy, Hache, A., Collard, K, Mackey, A., Gosselin-Lefebvre, S., Verreault, S., Beauchamp, B., Lambourn, L., Khaw, A., Mai, L., Sposato, L., Bres Bullrich, M., Azarpazhooh, R., Fridman, S., Kapoor, A., Southwell, A., Bardi, E., Fatakdawala, I., Kamra, M, Lopes, K., Popel, N., Norouzi, V., Liu, A., Liddy, A.M., Ghoari, B., Hawkes, C., Enriquez, C.A., Gladstone, D.J., Manosalva Alzate, H.A., Khosravani, H., Hopyan, J.J., Sivakumar, K., Son, M., Boulos, M.I., Hamind, M.A., Swartz, R.H., Murphy, R., Reiter, S., Fitzpatrick, T., Bhandari, V., Good, J., Penn, M., Naylor, M., Frost, S., Cayley, A., Akthar, F., Williams, J., Kalman, L., Crellin, L., Wiegner, R., Singh, R.S., Stewart, T., To, W., Singh, S., Pikula, A., Jaigobin, C., Carpani, F., Silver, F., Janssen, H., Schaafsma, J., del Campo, M., Alskaini, M., Rajendram, P., Fairall, P., Granfield, B., Crawford, D., Jabs, J., White, L., Sivakumar, L., Piquette, L., Nguyen, T., Nomani, A., Wagner, A., Alrohimi, A., Butt, A., D'Souza, A., Gajurel, B., Vekhande, C., Kamble, H., Kalashyan, H., Lloret, M., Benguzzi, M., Arsalan, N., Ishaque, N., Ashayeriahmadabad, R., Samiento, R., Hosseini, S., Kazi, S., Das, S., Sugumar, T., Selchen, D., Kostyrko, P., Muccilli, A., Saposnik, A.G., Vandervelde, C., Ratnayake, K., McMillan, S., Katsanos, A., Shoamanesh, A., Sahlas, D.J., Naidoo, V., Todorov, V., Toma, H., Brar, J., Lee, J., Horton, M., Shand, E., Weatherby, S., Jin, A., Durafourt, B., Jalini, S., Gardner, A., Tyson, C., Junk, E., Foster, K., Bolt, K., Sylvain, N., Maley, S., Urroz, L., Peeling, L., Kelly, M., Whelan, R., Cooley, R., Teitelbaum, J., Boutayeb, A., Moore, A., Cole, E., Waxman, L., Ben-Amor, N., Sanchez, R., Khalil, S., Nehme, A., Legault, C., Tampieri, D., Ehrensperger, E., Vieira, L., Cortes, M., Angle, M., Hannouche, M., Badawy, M., Werner, K., Wieszmuellner, S., Langer, A., Gisold, A., Zach, H., Rommer, P., Macher, S., Blechinger, S., Marik, W., Series, W., Baumgartinger, M., Krebs, S., Koski, J., Eirola, S., Ivanoff, T., Erakanto, A., Kupari, L., Sibolt, G., Panula, J., Tomppo, L., Tiainen, M., Ahlstrom, M., Martinez Majander, N., Suomalainen, O., Raty, S., Levi, C., Kerr, E., Allen, J., Kaauwai, L.P., Belevski, L., Russell, M., Ormond, S., Chew, A., Loiselle, A., Royan, A., Hughes, B., Garcia Esperon, C., Pepper, E., Miteff, F., He, J., Lycett, M., Min, M., Murray, N., Pavey, N., Starling de Barros, R., Gangadharan, S., Dunkerton, S., Waller, S., Canento Sanchez, T., Wellings, T., Edmonds, G., Whittaker, K.A., Ewing, M., Lee, P., Singkang, R., McDonald, A., Dos Santos, A., Shin, C., Jackson, D., Tsoleridis, J., Fisicchia, L., Parsons, N., Shenoy, N., Smith, S., Sharobeam, A., Balabanski, A., Park, A., Williams, C., Pavlin-Premri, D., Rodrigues, E., Alemseged, F., Ng, F., Zhao, H., Beharry, J., Ng, J.L., Williamson, J., Wong, J.Z.W., Li, K., Kwan, M.K., Valente, M., Yassi, N., Yogendrakumar, V., McNamara, B., Buchanan, C., McCarthy, C., Thomas, G., Stephens, K., Chung, M., Chung, M.F., Tang, M., Busch, T., Frost, T., Lee, R., Stuart, N., Pachani, N., Menon, A., Borojevic, B., Linton, C.M., Garcia, G., Callaly, E.P., Dewey, H., Liu, J., Chen, J., Wong, J., Nowak, K., To, K., Lizak, N.S., Bhalala, O., Park, P., Tan, P., Martins, R., Cody, R., Forbes, R., Chen, S.K., Ooi, S., Tu, S., Dang, Y.L., Ling, Z., Cranefield, J., Drew, R., Tan, A., Kurunawai, C., Harvey, J., Mahadevan, J.J., Cagi, L., Palanikumar, L., Chia, L.N., Goh, R., El-Masri, S., Urbi, B., Rapier, C., Berrill, H., McEvoy, H., Dunning, R., Kuriakose, S., Chad, T., Sapaen, V., Sabet, A., Shah, D., Yeow, D., Lilley, K., Ward, K., Mozhy Mahizhnan, M., Tan, M., Lynch, C., Coveney, S., Tobin, K., McCabe, J., Marnane, M., Murphy, S., Large, M., Moynihan, B., Boyle, K., Sanjuan, E., Sanchis, M., Boned, S., Pancorbo, O., Sala, V., Garcia, L., Garcia-Tornel, A., Juega, J., Pagola, J., Santana, K., Requena, M., Muchada, M., Olive, M., Lozano, P.J., Rubiera, M., Deck, M., Rodriguez, N., Gomez, B., Reyes Munoz, F.J., Gomez, A.S., Sanz, A.C., Garcia, E.C., Penacoba, G., Ramos, M.E., de Lera Alfonso, M., Feliu, A, Pardo, L., Ramirez, P., Murillo, A., Lopez Dominguez, D., Rodriguez, J., Terceno Izaga, M., Reina, M., Viturro, S.B., Bojaryn, U., Vera Monge, V.A., Silva Blas, Y., R Siew, R., Agustin, S J, Seet, C., Tianming, T., d'Emden, A., Murray, A., Welch, A., Hatherley, K., Day, N., Smith, W., MacRae, E., Mitchell, E.S., Mahmood, A., Elliot, J., Neilson, S., Biswas, V., Brown, C., Lewis, A., Ashton, A., Werring, D., Perry, R., Muhammad, R., Lee, Y.C., Black, A., Robinson, A., Williams, A., Banaras, A., Cahoy, C., Raingold, G., Marinescu, M., Atang, N., Bason, N., Francia, N., Obarey, S., Feerick, S., Joseph, J., Schulz, U., Irons, R., Benjamin, J., Quinn, L., Jhoots, M., Teal, R., Ford, G., Harston, G., Bains, H., Gbinigie, I., Mathieson, P., Sim, C.H., Hayter, E., Kennedy, K., Binnie, L., Priestley, N., Williams, R., Ghatala, R., Stratton, S., Blight, A., Zhang, L., Davies, A., Duffy, H., Roberts, J., Homer, J., Roberts, K., Dodd, K., Cawley, K., Martin, M., Leason, S., Cotgreave, S., Taylor, T., Nallasivan, A., Haider, S., Chakraborty, T., Webster, T., Gil, A., Martin, B., Joseph, B., Cabrera, C., Jose, D., Man, J., Aquino, J., Sebastian, S., Osterdahl, M., Kwan, M., Matthew, M., Ike, N., Bello, P., Wilding, P., Fuentes, R., Shah, R., Mashate, S., Patel, T., Nwanguma, U., Dave, V., Haber, A., Lee, A., O'Sullivan, A., Drumm, B., Dawson, A.C., Matar, T., Roberts, D., Taylor, E., Rounis, E., El-Masry, A., O'Hare, C., Kalladka, D., Jamil, S., Auger, S., Raha, O., Evans, M., Vonberg, F., Kalam, S., Ali Sheikh, A., Jenkins, I.H., George, J., Kwan, J., Blagojevic, J., Saeed, M., Haji-Coll, M., Tsuda, M., Sayed, M., Winterkron, N., Thanbirajah, N., Vittay, O., Karim, R., Smail, R.C., Gauhar, S., Elmamoun, S., Malani, S., Pralhad Kelavkar, S., Hiden, J., Ferdinand, P., Sanyal, R., Varquez, R., Smith, B., Okechukwu, C., Fox, E., Collins, E., Courtney, K., Tauro, S., Patterson, C., McShane, D., Roberts, G., McIImoyle, J., McGuire, K., Fearon, P., Gordon, P., Isaacs, K., Lucas, K., Smith, L., Dews, L., Bates, M., Lawrence, S., Heeley, S., Patel, V., Chin, Y.M., Sims, D., Littleton, E., Khaira, J., Nadar, K., Kieliszkowska, A., Sari, B., Domingos Belo, C., Smith, E., Manolo, E.Y., Aeron-Thomas, J., Doheny, M., Garcia Pardo, M., Recaman, M., Tibajia, M.C., Aissa, M., Mah, Y., Yu, T., Meenakshisundaram, S., Heller, S., Alsukhni, R., Williams, O., Farag, M., Benger, M., Engineer, A., Bayhonan, S., Conway, S., Bhalla, A., Nouvakis, D., Theochari, E., Boyle, F., Teo, J., King-Robson, J., Law, K.Y., Sztriha, L., McGovern, A., Day, D., Mitchell-Douglas, J., Francis, J., Iqbal, A., Punjabivaryani, P., Anonuevo Reyes, J., Anonuevo Reyes, M., Pauls, M., Buch, A., Hedstrom, A., Hutchinson, C., Kirkland, C., Newham, J., Wilkes, G., Fleming, L., Fleck, N., Franca, A., Chwal, B., Oldoni, C., Mantovani, G., Noll, G., Zanella, L., Soma, M., Secchi, T., Borelli, W., Rimoli, B.P., da Cunha Silva, G.H., Machado Galvao Mondin, L.A., Barbosa Cerantola, R., Imthon, A.K., Esaki, A.S., Camilo, M., Vincenzi, O.C., ds Cruz, R.R., Morillos, M.B., Riccioppa Rodrigues, G.G., Santos Ferreira, K., Pazini, A.M., Pena Pereira, M.A., de Albuquerque, A.L.A., Massote Fontanini, C.E., Matinez Rubio, C.F., dos Santos, D.T., Dias, F.A., Alves, F.F.A., Milani, C., Pegorer Santos, B., Winckler, F., De Souza, J.T., Bonome, L.A.M., Cury Silva, V.A., Teodoro, R.S., Modolo, G.P., Ferreira, N.C., Barbosa dos Santos, D.F., dos Santos Moreira, J.C., Cruz Guedes de Morais, A.B., Vieira, J., Mendes, G., de Queiroz, J.P., Coutts, Shelagh B, Ankolekar, Sandeep, Appireddy, Ramana, Arenillas, Juan F, Assis, Zarina, Bailey, Peter, Barber, Philip A, Bazan, Rodrigo, Buck, Brian H, Butcher, Ken S, Camden, Marie-Christine, Campbell, Bruce C V, Casaubon, Leanne K, Catanese, Luciana, Chatterjee, Kausik, Choi, Philip M C, Clarke, Brian, Dowlatshahi, Dar, Ferrari, Julia, Field, Thalia S, Ganesh, Aravind, Ghia, Darshan, Goyal, Mayank, Greisenegger, Stefan, Halse, Omid, Horn, Mackenzie, Hunter, Gary, Imoukhuede, Oje, Kelly, Peter J, Kennedy, James, Kleinig, Timothy J, Krishnan, Kailash, Lima, Fabricio, Mandzia, Jennifer L, Marko, Martha, Martins, Sheila O, Medvedev, George, Menon, Bijoy K, Mishra, Sachin M, Molina, Carlos, Moussaddy, Aimen, Muir, Keith W, Parsons, Mark W, Penn, Andrew M W, Pille, Arthur, Pontes-Neto, Octávio M, Roffe, Christine, Serena, Joaquin, Simister, Robert, Singh, Nishita, Spratt, Neil, Strbian, Daniel, Tham, Carol H, Wiggam, M Ivan, Williams, David J, Willmot, Mark R, Wu, Teddy, Yu, Amy Y X, Zachariah, George, Zafar, Atif, Zerna, Charlotte, and Hill, Michael D

Published
2024
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4. Transcriptional regulation of the Ccn2 gene

Author

Frost, S. L., Bou-Gharios, George, Comerford, Eithne, and Poulet, Blandine

Subjects
618.97
Abstract

Cellular Communication Network Factor 2 (CCN2) is a matricellular protein which functions in many tissues, and is most notably expressed by chondrocytes, with knockout of the Ccn2 gene expression causing severe chondrodysplasia in mice. Regulation at the prerequisite stage of transcription by non-coding genomic elements is fundamental in the expression of every gene. Until now, the capacity for cis-acting regulatory modules to control the expression of Ccn2 has been obscure. The current project sought to delineate the capacity for cis-acting enhancer regions to regulate Ccn2 transcription within highly specific temporospatial contexts. A 300 kilobase intergenic genomic region upstream of Ccn2 was examined in silico in order to identify putative enhancer regions based on chromatin characteristics of enhancers; histone modification, DNase I hypersensitivity and interspecies evolutionary conservation of DNA sequence. Transgenic mice were created using constructs consisting of each putative enhancer region driving the expression of a LacZ reporter gene in conjunction with a silent Hsp68 minimal promoter. Expression of the protein product of LacZ, β-galactosidase was assayed at several developmental time-points in order to determine whether candidate enhancers were able to control gene transcription. Five enhancer regions of murine Ccn2 expression, located -230kb, -198kb, -148kb, -137kb and -102kb upstream of the gene each drove LacZ expression in a tissue-specific manner at embryonic day E15.5. -230kb drove transgene activity within osteoblasts, whereas -198kb, -148kb and -137kb all exhibited function within chondrocytes. The -102kb enhancer was active within the superficial vasculature. More comprehensive examination of the - 148kb enhancer revealed function in adulthood, and that a truncated region of this sequence is also capable of enhancing gene transcriptional output. Enhancer sequences were also examined in vitro using Electrophoretic Mobility Shift Assay in order to test the capacity of transcription factors of interest to bind to enhancers and modulate function. Master regulator of chondrocyte physiology, the transcription factor SOX9 was found to bind to sequences within the -137kb, -148kb and -230kb enhancers. The findings described herein are the first to characterise the role of cis-acting enhancer regions in the transcription of Ccn2 within the murine genome. Understanding the mechanisms that underpin temporospatial control of Ccn2 expression will inform both the characterisation and amelioration of profound pathological conditions that result from loss of CCN2 transcriptional regulation such as osteoarthritis, fibrosis and cancer in humans.

Published
2019
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6. Tenecteplase versus standard of care for minor ischaemic stroke with proven occlusion (TEMPO-2): a randomised, open label, phase 3 superiority trial

Author

Coutts, Shelagh B, Ankolekar, Sandeep, Appireddy, Ramana, Arenillas, Juan F, Assis, Zarina, Bailey, Peter, Barber, Philip A, Bazan, Rodrigo, Buck, Brian H, Butcher, Ken S, Camden, Marie-Christine, Campbell, Bruce C V, Casaubon, Leanne K, Catanese, Luciana, Chatterjee, Kausik, Choi, Philip M C, Clarke, Brian, Dowlatshahi, Dar, Ferrari, Julia, Field, Thalia S, Ganesh, Aravind, Ghia, Darshan, Goyal, Mayank, Greisenegger, Stefan, Halse, Omid, Horn, Mackenzie, Hunter, Gary, Imoukhuede, Oje, Kelly, Peter J, Kennedy, James, Kenney, Carol, Kleinig, Timothy J, Krishnan, Kailash, Lima, Fabricio, Mandzia, Jennifer L, Marko, Martha, Martins, Sheila O, Medvedev, George, Menon, Bijoy K, Mishra, Sachin M, Molina, Carlos, Moussaddy, Aimen, Muir, Keith W, Parsons, Mark W, Penn, Andrew M W, Pille, Arthur, Pontes-Neto, Octávio M, Roffe, Christine, Serena, Joaquin, Simister, Robert, Singh, Nishita, Spratt, Neil, Strbian, Daniel, Tham, Carol H, Wiggam, M Ivan, Williams, David J, Willmot, Mark R, Wu, Teddy, Yu, Amy Y X, Zachariah, George, Zafar, Atif, Zerna, Charlotte, Hill, Michael D, Salluzzi, Marina, Blenkin, Nicole, Dueck, Ashley, Doram, Craig, Zhang, Qiao, Kenney, Carol, Ryckborst, Karla, Bohn, Shelly, Collier, Quentin, Taylor, Frances, Lethebe, B. Cord, Jambula, Anitha, Sage, Kayla, Toussaint, Lana, Save, Supryia, Lee, Jaclyn, Laham, N, Sultan, A.A., Deepak, A., Sitaram, A., Demchuk, Andrew M., Lockey, A., Micielli, A., Wadhwa, A., Arabambi, B., Graham, B., Bogiatzi, Chrysi, Doshi, Darshan, Chakraborty, D., Kim, Diana, Vasquez, D, Singh, D, Tse, Dominic, Harrison, E., Smith, E.E., Teleg, E., Klourfeld, E., Klein, G., Sebastian, I.A., Evans, J, Hegedus, J, Kromm, J, Lin, K, Ignacio, K, Ghavami, Kimia, Ismail, M., Moores, M., Panzini, M.A., Boyko, M., Almekhlafi, M.A., Newcommon, Nancy, Maraj, N., Imoukhuede, O., Volny, O., Stys, Peter, Couillard, Phillipe, Ojha, P., Eswaradass, P., Joundi, Raed, Singh, R., Asuncion, R.M., Muir, R.T., Dey, S., Mansoor, S., Wasyliw, S., Nagendra, S., Hu, Sherry, Althubait, S., Chen, S., Bal, S., Van Gaal, Stephen, Peters, Steven, Ray, Sucharita, Chaturvedi, S., Subramaniam, Suresh, Fu, Vivian, Villaluna, K., Maclean, G., King-Azote, P., Ma, C., Plecash, A., Murphy, C., Gorman, J., Wilson, L., Zhou, L., Benevente, O., Teal, P., Yip, S., Mann, S., Dewar, B., Demetroff, M., Shamloul, R., Beardshaw, R., Roberts, S., Blaquiere, D., Stotts, G., Shamy, M., Bereznyakova, O., Fahed, R., Alesefir, W., Lavoie, Suzy, Hache, A., Collard, K, Mackey, A., Gosselin-Lefebvre, S., Verreault, S., Beauchamp, B., Lambourn, L., Khaw, A., Mai, L., Sposato, L., Bres Bullrich, M., Azarpazhooh, R., Fridman, S., Kapoor, A., Southwell, A., Bardi, E., Fatakdawala, I., Kamra, M, Lopes, K., Popel, N., Norouzi, V., Liu, A., Liddy, A.M., Ghoari, B., Hawkes, C., Enriquez, C.A., Gladstone, D.J., Manosalva Alzate, H.A., Khosravani, H., Hopyan, J.J., Sivakumar, K., Son, M., Boulos, M.I., Hamind, M.A., Swartz, R.H., Murphy, R., Reiter, S., Fitzpatrick, T., Bhandari, V., Good, J., Penn, M., Naylor, M., Frost, S., Cayley, A., Akthar, F., Williams, J., Kalman, L., Crellin, L., Wiegner, R., Singh, R.S., Stewart, T., To, W., Singh, S., Pikula, A., Jaigobin, C., Carpani, F., Silver, F., Janssen, H., Schaafsma, J., del Campo, M., Alskaini, M., Rajendram, P., Fairall, P., Granfield, B., Crawford, D., Jabs, J., White, L., Sivakumar, L., Piquette, L., Nguyen, T., Nomani, A., Wagner, A., Alrohimi, A., Butt, A., D'Souza, A., Gajurel, B., Vekhande, C., Kamble, H., Kalashyan, H., Lloret, M., Benguzzi, M., Arsalan, N., Ishaque, N., Ashayeriahmadabad, R., Samiento, R., Hosseini, S., Kazi, S., Das, S., Sugumar, T., Selchen, D., Kostyrko, P., Muccilli, A., Saposnik, A.G., Vandervelde, C., Ratnayake, K., McMillan, S., Katsanos, A., Shoamanesh, A., Sahlas, D.J., Naidoo, V., Todorov, V., Toma, H., Brar, J., Lee, J., Horton, M., Chen, S., Shand, E., Weatherby, S., Jin, A., Durafourt, B., Jalini, S., Gardner, A., Tyson, C., Junk, E., Foster, K., Bolt, K., Sylvain, N., Maley, S., Urroz, L., Peeling, L., Kelly, M., Whelan, R., Cooley, R., Teitelbaum, J., Boutayeb, A., Moore, A., Cole, E., Waxman, L., Ben-Amor, N., Sanchez, R., Khalil, S., Nehme, A., Legault, C., Tampieri, D., Ehrensperger, E., Vieira, L., Cortes, M., Angle, M., Hannouche, M., Badawy, M., Werner, K., Wieszmuellner, S., Langer, A., Gisold, A., Zach, H., Rommer, P., Macher, S., Blechinger, S., Marik, W., Series, W., Baumgartinger, M., Krebs, S., Koski, J., Eirola, S., Ivanoff, T., Erakanto, A., Kupari, L., Sibolt, G., Panula, J., Tomppo, L., Tiainen, M., Ahlstrom, M., Martinez Majander, N., Suomalainen, O., Raty, S., Levi, C., Kerr, E., Allen, J., Kaauwai, L.P., Belevski, L., Russell, M., Ormond, S., Chew, A., Loiselle, A., Royan, A., Hughes, B., Garcia Esperon, C., Pepper, E., Miteff, F., He, J., Lycett, M., Min, M., Murray, N., Pavey, N., Starling de Barros, R., Gangadharan, S., Dunkerton, S., Waller, S., Canento Sanchez, T., Wellings, T., Edmonds, G., Whittaker, K.A., Ewing, M., Lee, P., Singkang, R., McDonald, A., Dos Santos, A., Shin, C., Jackson, D., Tsoleridis, J., Fisicchia, L., Parsons, N., Shenoy, N., Smith, S., Sharobeam, A., Balabanski, A., Park, A., Williams, C., Pavlin-Premri, D., Rodrigues, E., Alemseged, F., Ng, F., Zhao, H., Beharry, J., Ng, J.L., Williamson, J., Wong, J.Z.W., Li, K., Kwan, M.K., Valente, M., Yassi, N., Cooley, R., Yogendrakumar, V., McNamara, B., Buchanan, C., McCarthy, C., Thomas, G., Stephens, K., Chung, M., Chung, M.F., Tang, M., Busch, T., Frost, T., Lee, R., Stuart, N., Pachani, N., Menon, A., Borojevic, B., Linton, C.M., Garcia, G., Callaly, E.P., Dewey, H., Liu, J., Chen, J., Wong, J., Nowak, K., To, K., Lizak, N.S., Bhalala, O., Park, P., Tan, P., Martins, R., Cody, R., Forbes, R., Chen, S.K., Ooi, S., Tu, S., Dang, Y.L., Ling, Z., Cranefield, J., Drew, R., Tan, A., Kurunawai, C., Harvey, J., Mahadevan, J.J., Cagi, L., Palanikumar, L., Chia, L.N., Goh, R., El-Masri, S., Urbi, B., Rapier, C., Berrill, H., McEvoy, H., Dunning, R., Kuriakose, S., Chad, T., Sapaen, V., Sabet, A., Shah, D., Yeow, D., Lilley, K., Ward, K., Mozhy Mahizhnan, M., Tan, M., Lynch, C., Coveney, S., Tobin, K., McCabe, J., Marnane, M., Murphy, S., Large, M., Moynihan, B., Boyle, K., Sanjuan, E., Sanchis, M., Boned, S., Pancorbo, O., Sala, V., Garcia, L., Garcia-Tornel, A., Juega, J., Pagola, J., Santana, K., Requena, M., Muchada, M., Olive, M., Lozano, P.J., Rubiera, M., Deck, M., Rodriguez, N., Gomez, B., Reyes Munoz, F.J., Gomez, A.S., Sanz, A.C., Garcia, E.C., Penacoba, G., Ramos, M.E., de Lera Alfonso, M., Feliu, A, Pardo, L., Ramirez, P., Murillo, A., Lopez Dominguez, D., Rodriguez, J., Terceno Izaga, M., Reina, M., Viturro, S.B., Bojaryn, U., Vera Monge, V.A., Silva Blas, Y., R Siew, R., Agustin, S J, Seet, C., Tianming, T., d'Emden, A., Murray, A., Welch, A., Hatherley, K., Day, N., Smith, W., MacRae, E., Mitchell, E.S., Mahmood, A., Elliot, J., Neilson, S., Biswas, V., Brown, C., Lewis, A., Ashton, A., Werring, D., Perry, R., Muhammad, R., Lee, Y.C., Black, A., Robinson, A., Williams, A., Banaras, A., Cahoy, C., Raingold, G., Marinescu, M., Atang, N., Bason, N., Francia, N., Obarey, S., Feerick, S., Joseph, J., Schulz, U., Irons, R., Benjamin, J., Quinn, L., Jhoots, M., Teal, R., Ford, G., Harston, G., Bains, H., Gbinigie, I., Mathieson, P., Irons, R., Sim, C.H., Hayter, E., Kennedy, K., Binnie, L., Priestley, N., Williams, R., Ghatala, R., Stratton, S., Blight, A., Zhang, L., Davies, A., Duffy, H., Roberts, J., Homer, J., Roberts, K., Dodd, K., Cawley, K., Martin, M., Leason, S., Cotgreave, S., Taylor, T., Nallasivan, A., Haider, S., Chakraborty, T., Webster, T., Gil, A., Martin, B., Joseph, B., Cabrera, C., Jose, D., Man, J., Aquino, J., Sebastian, S., Osterdahl, M., Kwan, M., Matthew, M., Ike, N., Bello, P., Wilding, P., Fuentes, R., Shah, R., Mashate, S., Patel, T., Nwanguma, U., Dave, V., Haber, A., Lee, A., O'Sullivan, A., Drumm, B., Dawson, A.C., Matar, T., Biswas, V., Roberts, D., Taylor, E., Rounis, E., El-Masry, A., O'Hare, C., Kalladka, D., Jamil, S., Auger, S., Raha, O., Evans, M., Vonberg, F., Kalam, S., Ali Sheikh, A., Jenkins, I.H., George, J., Kwan, J., Blagojevic, J., Saeed, M., Haji-Coll, M., Tsuda, M., Sayed, M., Winterkron, N., Thanbirajah, N., Vittay, O., Karim, R., Smail, R.C., Gauhar, S., Elmamoun, S., Malani, S., Pralhad Kelavkar, S., Hiden, J., Ferdinand, P., Sanyal, R., Varquez, R., Smith, B., Okechukwu, C., Fox, E., Collins, E., Courtney, K., Tauro, S., Patterson, C., McShane, D., Kerr, E., Roberts, G., McIImoyle, J., McGuire, K., Fearon, P., Gordon, P., Isaacs, K., Lucas, K., Smith, L., Dews, L., Bates, M., Lawrence, S., Heeley, S., Patel, V., Chin, Y.M., Sims, D., Littleton, E., Khaira, J., Nadar, K., Kieliszkowska, A., Sari, B., Domingos Belo, C., Smith, E., Manolo, E.Y., Aeron-Thomas, J., Doheny, M., Garcia Pardo, M., Recaman, M., Tibajia, M.C., Aissa, M., Mah, Y., Yu, T., Patel, V., Meenakshisundaram, S., Heller, S., Alsukhni, R., Williams, O., Farag, M., Benger, M., Engineer, A., Aissa, M., Bayhonan, S., Conway, S., Bhalla, A., Nouvakis, D., Theochari, E., Boyle, F., Teo, J., King-Robson, J., Law, K.Y., Sztriha, L., Ismail, M., McGovern, A., Day, D., Mitchell-Douglas, J., Francis, J., Iqbal, A., Punjabivaryani, P., Anonuevo Reyes, J., Anonuevo Reyes, M., Pauls, M., Buch, A., Hedstrom, A., Hutchinson, C., Kirkland, C., Newham, J., Wilkes, G., Fleming, L., Fleck, N., Franca, A., Chwal, B., Oldoni, C., Mantovani, G., Noll, G., Zanella, L., Soma, M., Secchi, T., Borelli, W., Rimoli, B.P., da Cunha Silva, G.H., Machado Galvao Mondin, L.A., Barbosa Cerantola, R., Imthon, A.K., Esaki, A.S., Camilo, M., Vincenzi, O.C., ds Cruz, R.R., Morillos, M.B., Riccioppa Rodrigues, G.G., Santos Ferreira, K., Pazini, A.M., Pena Pereira, M.A., de Albuquerque, A.L.A., Massote Fontanini, C.E., Matinez Rubio, C.F., dos Santos, D.T., Dias, F.A., Alves, F.F.A., Milani, C., Pegorer Santos, B., Winckler, F., De Souza, J.T., Bonome, L.A.M., Cury Silva, V.A., Teodoro, R.S., Modolo, G.P., Ferreira, N.C., Barbosa dos Santos, D.F., dos Santos Moreira, J.C., Cruz Guedes de Morais, A.B., Vieira, J., Mendes, G., and de Queiroz, J.P.

Abstract

Individuals with minor ischaemic stroke and intracranial occlusion are at increased risk of poor outcomes. Intravenous thrombolysis with tenecteplase might improve outcomes in this population. We aimed to test the superiority of intravenous tenecteplase over non-thrombolytic standard of care in patients with minor ischaemic stroke and intracranial occlusion or focal perfusion abnormality.

Published
2024
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11. Study protocol for Care cOORDInatioN And sympTom managEment (COORDINATE) programme: a feasibility study.

Author

Koirala, B, Badawi, S, Frost, S, Ferguson, C, Hager, DN, Street, L, Perrin, N, Dennison Himmelfarb, C, Davidson, P, Koirala, B, Badawi, S, Frost, S, Ferguson, C, Hager, DN, Street, L, Perrin, N, Dennison Himmelfarb, C, and Davidson, P

Abstract

INTRODUCTION: Sustainable approaches to support care coordination and symptom management needs of critically ill adults living with multimorbidity are needed to combat the challenges and complexity that multimorbidity presents. The study aims to test the feasibility of the Care cOORDInatioN And sympTom managEment (COORDINATE) intervention to improve health outcomes of adults living with multimorbidity. METHODS AND ANALYSIS: A multicomponent nurse-driven intervention was developed using experience-based co-design and human-centred design. Inclusion criteria include (1) age 55 years and older, (2) admitted to an intermediate care unit, (3) presence of two or more chronic health conditions and (4) signed informed consent. Data collection will occur at baseline (time of recruitment predischarge) and 6 weeks and 3 months following hospital discharge. Outcome of interest from this feasibility study is to evaluate the financial, technical and logistic feasibility of a full-scale study including data collection and protocol adherence. Additionally, Cohen's d effect sizes for the change in outcomes over time will be computed to establish power calculations required for a full-scale study. The protocol was prepared in accordance with Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist. ETHICS AND DISSEMINATION: The study has been reviewed and approved by the Institutional Review Board of Johns Hopkins Medical Institutions. Given the success of this feasibility study, the potential for the COORDINATE intervention to decrease the symptom burden and improve participant quality of life among critically ill people with multimorbidity will be tested in a full-scale study, and findings will be actively disseminated. TRIAL REGISTRATION NUMBER: NCT05985044.

Published
2023

12. BONEcheck: A digital tool for personalized bone health assessment.

Author

Nguyen, DT, Ho-Le, TP, Pham, L, Ho-Van, VP, Hoang, TD, Tran, TS, Frost, S, Nguyen, TV, Nguyen, DT, Ho-Le, TP, Pham, L, Ho-Van, VP, Hoang, TD, Tran, TS, Frost, S, and Nguyen, TV

Abstract

OBJECTIVES: Osteoporotic fracture is a significant public health burden associated with increased mortality risk and substantial healthcare costs. Accurate and early identification of high-risk individuals and mitigation of their risks is a core part of the treatment and prevention of fractures. Here we introduce a digital tool called 'BONEcheck' for personalized assessment of bone health. METHODS: The development of BONEcheck primarily utilized data from the prospective population-based Dubbo Osteoporosis Epidemiology Study and the Danish Nationwide Registry. BONEcheck has 3 modules: input data, risk estimates, and risk context. Input variables include age, gender, prior fracture, fall incidence, bone mineral density (BMD), comorbidities, and genetic variants associated with BMD. RESULTS: Based on the input variables, BONEcheck estimates the probability of any fragility fracture and hip fracture within 5 years, subsequent fracture risk, skeletal age, and time to reach osteoporosis. The probability of fracture is shown in both numeric and human icon array formats. The risk is also contextualized within the framework of treatment and management options on Australian guidelines, with consideration given to the potential fracture risk reduction and survival benefits. Skeletal age was estimated as the sum of chronological age and years of life lost due to a fracture or exposure to risk factors that elevate mortality risk. CONCLUSIONS: BONEcheck is an innovative tool that empowers doctors and patients to engage in well-informed discussions and make decisions based on the patient's risk profile. Public access to BONEcheck is available via https://bonecheck.org and in Apple Store (iOS) and Google Play (Android).

Published
2023

13. Analytical applications of liposomes

Author

Frost, S. J.

Subjects
615.1, Drug delivery
Abstract

Liposomes have established roles in drug delivery and cell membrane studies. Amongst other applications; they can also be used as analytical reagents, particularly in immunoassays. Liposomal immunoassays have potential advantages over alternatives; including sensitivity, speed, simplicity and relative reagent stability. The aim of these studies was to develop and evaluate novel examples of these assays. When liposomes entrapped the dye, Sulphorhodamine B, a shift in its maximum absorption wavelength compared to free dye was observed. This was attributed to dimerization of the dye at high concentrations. If the liposomes were disrupted, the released dye was diluted into the external buffer, and the dye's absorption spectrum reverted to that of free dye. After optimization of dye entrapment, immunoassays were developed using these liposomes. Albumin-coated liposomes were used in a model assay to measure serum albumin. This assay employed complement-mediated immunolysis, commonly used in liposomal immunoassays. The liposomes were lysed by anti-albumin and complement, and this could be competitively inhibited by serum albumin. To improve sensitivity, Fab' anti-albumin liposomes were prepared. These enabled measurement of urinary albumin by a complement-mediated immunoassay, but using a sandwich technique. Anti-albumin (intact) liposomes were shown to precipitate on gentle centrifugation after reaction with albumin. They were applied as a solid phase reagent in an heterogeneous immunoassay, using radioimmunoassay for urinary microalbumin as a model assay. Liposomes containing Sulphorhodamine B were also used in a more novel assay; for serum anticardiolipin antibodies. Cardiolipin-containing liposomes were prepared. These were lysable using magnesium ions. Anticardiolipin antibodies (IgG) were found to augment this lysis, enabling their estimation. Similar imprecision and acceptable correlation with a commercial enzyme-linked immunosorbent assay (ELISA) were obtained. The findings demonstrate Sulphorhodamine B release can be used as a marker in homogeneous colorimetric liposomal immunoassays; both in model assays and in potentially more useful clinical biochemistry applications.

Published
1994

19. Novel Setting for Addressing Tobacco-Related Disparities: A Survey of Community Welfare Organization Smoking Policies, Practices and Attitudes

Author

Bonevski, B., O'Brien, J., Frost, S., Yiow, L., Oakes, W., and Barker, D.

Abstract

Research in the United States and Australia acknowledges the potential of non-government social and community service organizations (SCSOs) for reaching socially disadvantaged smokers. This study aimed to describe SCSO smoking policies and practices, and attitudes of senior staff towards smoking and cessation. It also investigated factors associated with positive tobacco control attitudes. In 2009, a cross-sectional telephone survey was undertaken of senior staff in Australian SCSOs, 149 respondents representing 93 organizations completed the survey (response rate = 65%; 93/142). Most service clients (60%) remained in programs for 6 months plus, and 77% attended at least weekly. Although 93% of respondents indicated they had an organizational smoking policy, it often did not include the provision of smoking cessation support. Most respondents indicated that client smoking status was not recorded on case notes (78%). Attitudes were mostly positive towards tobacco control in SCSOs, with a mean (standard deviation) score of 8.3 (2.9) of a possible 13. The practice of assessing clients' interest in quitting was the only statistically significant factor associated with high tobacco control attitude scores. The results suggest that SCSOs are appropriate settings for reaching socially disadvantaged smokers with cessation support. Although generally receptive to tobacco control, organizations require further support to integrate smoking cessation support into usual care. In particular, education, training and support for staff to enable them to help their clients quit smoking is important. (Contains 1 figure and 4 tables.)

Published
2013
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29. War, Famine, and Environment in Eritrea.

Author

Horne, R. E. and Frost, S.

Abstract

Discusses the armed struggle in Eritrea between 1981 and 1991 and its contributions to environmental degradation and famine in this area. Examines the future prospects of Eritrea in the context of the African development experience. (22 references) (MDH)

Published
1992

30. Genetic Engineering and Crop Production.

Author

Jones, Helen C. and Frost, S.

Abstract

With a spotlight upon current agricultural difficulties and environmental dilemmas, this paper considers both the extant and potential applications of genetic engineering with respect to crop production. The nonagricultural factors most likely to sway the impact of this emergent technology upon future crop production are illustrated. (JJK)

Published
1991

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