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2. Dexmedetomidine and Propofol Sedation in Critically Ill Patients and Dose-associated 90-Day Mortality: A Secondary Cohort Analysis of a Randomized Controlled Trial (SPICE III)

Author

Shehabi, Yahya, primary, Serpa Neto, Ary, additional, Bellomo, Rinaldo, additional, Howe, Belinda D., additional, Arabi, Yaseen M., additional, Bailey, Michael, additional, Bass, Frances E., additional, Bin Kadiman, Suhaini, additional, McArthur, Colin J., additional, Reade, Michael C., additional, Seppelt, Ian M., additional, Takala, Jukka, additional, Wise, Matt P., additional, Webb, Steve A., additional, Mashonganyika, C., additional, McKee, H., additional, Tonks, A., additional, Donnelly, A., additional, Hemmings, N., additional, O’Kane, S., additional, Blakemore, A., additional, Butler, M., additional, Cowdrey, K., additional, Dalton, J., additional, Gilder, E., additional, Long, S., additional, McCarthy, L., additional, McGuinness, S., additional, Parke, R., additional, Chen, Y., additional, McArthur, C., additional, McConnochie, R., additional, Newby, L., additional, Bellomo, R., additional, Eastwood, G., additional, Peck, L., additional, Young, H., additional, Boschert, C., additional, Edington, J., additional, Fletcher, J., additional, Smith, J., additional, Nand, K., additional, Raza, A., additional, Sara, T., additional, Bennett-Britton, J., additional, Bewley, J., additional, Bodenham, V., additional, Cole, L., additional, Driver, K., additional, Grimmer, L., additional, Howie, L., additional, Searles, C., additional, Sweet, K., additional, Webster, D., additional, van Berkel, A., additional, Connor, H., additional, Dennett, J., additional, van Der Graaff, M., additional, Henderson, S., additional, Mehrtens, J., additional, Miller, K., additional, Minto, E., additional, Morris, A., additional, Noble, S., additional, Parker, K., additional, Bulfin, L., additional, Hart, N., additional, Shepherd, K., additional, Vij, S., additional, Dickson, S., additional, Elloway, E., additional, Ferguson, C., additional, Jackson, R., additional, MacNaughton, P., additional, Marner, M., additional, Squire, R., additional, Waddy, S., additional, Wafer, P., additional, Welbourne, J., additional, Ashcroft, P., additional, Chambler, D., additional, Dukes, S., additional, Harris, A., additional, Horton, S., additional, Sharpe, S., additional, Williams, P., additional, Williams, S., additional, Bailey, M., additional, Blazquez, E., additional, France, D., additional, Hutchison, R., additional, O’Connor, A., additional, Comadira, G., additional, Gough, M., additional, Tallott, M., additional, Bastick, M., additional, Cameron, R., additional, Donovan, S., additional, Ellis, K., additional, Gaur, A., additional, Gregory, R., additional, Naumoff, J., additional, Turner, E., additional, White, M., additional, Au, K. F. J., additional, Fratzia, J., additional, Treloar, S., additional, Lim, C. H., additional, Maseeda, Y., additional, Tan, A. P., additional, Tang, C. L., additional, Yong, C. Y., additional, Akaltan, M., additional, Berger, S., additional, Blaser, D., additional, Fazlija, L., additional, Jong, M. L., additional, Lensch, M., additional, Ludwig, R., additional, Merz, T., additional, Nettelbeck, K., additional, Roth, M., additional, Schafer, M., additional, Takala, J., additional, Wehr, A., additional, Zacharias, D., additional, Amran, R., additional, Ashraf, H. N., additional, Azmi, N., additional, Basri, N., additional, Burhanuddin, H., additional, Hadinata, Y., additional, Hamdan, A., additional, Kadiman, S., additional, Rashid, A. I. Y. M., additional, Sabran, I. N., additional, Sulaiman, S., additional, Zabidi, I. N., additional, Al-Dawood, A., additional, Aljuaid, M., additional, Anizi, H. Al, additional, Saeedi, A. Al, additional, Arabi, Y., additional, Dbsawy, M., additional, Deeb, A., additional, Hegazy, M., additional, Magdi, I., additional, Clarey, E., additional, Corcoran, E., additional, Finney, C., additional, Harris, C., additional, Hopkins, P., additional, Noble, H., additional, Thompson, L., additional, Williams, T., additional, Dumlao, L. A., additional, Bassam, R., additional, Hassan, M. A., additional, Naseem, N., additional, Al-Kurdi, M. H., additional, Al-Harthy, A. M., additional, Bernard, S., additional, Sebafundi, L., additional, Serban, C., additional, Lim, S. K., additional, Mazidah, N., additional, Saidin, N., additional, Sjamsuddin, N., additional, Tan, I. T. A., additional, Zabidi, N., additional, Brain, M., additional, Mineall, S., additional, Kanhere, M., additional, Soar, N., additional, Kadir, N. Abd, additional, Abdullah, N. H., additional, Awang, R., additional, Emperan, Z., additional, Husin, N. S., additional, Ismail, N. I., additional, Ismail, S. Z., additional, Khadzali, F. N. A. Mohd, additional, Norddin, M. F., additional, Aguila, J., additional, Bold, C., additional, Clatworthy, B., additional, Dias, A., additional, Hogan, C., additional, Kazemi, A., additional, Lai, V., additional, Song, R., additional, Williams, A., additional, Bhatia, D., additional, Elliot, S., additional, Galt, P., additional, Lavrans, K., additional, Ritchie, P., additional, Wang, A., additional, Gresham, R., additional, Lowrey, J., additional, Masters, K., additional, Palejs, P., additional, Seppelt, I., additional, Symonds, F., additional, Weisbrodt, L., additional, Whitehead, C., additional, Babio-Galan, M., additional, Calder, V., additional, Clement, I., additional, Harrison, A., additional, McCullagh, I., additional, Scott, C., additional, Bevan, R., additional, Caniba, S., additional, Hacking, D., additional, Maher, L., additional, Azzolini, M. L., additional, Beccaria, P., additional, Colombo, S., additional, Landoni, G., additional, Leggieri, C., additional, Luca, C., additional, Mamo, D., additional, Moizo, E., additional, Monti, G., additional, Mucci, M., additional, Zangrillo, A., additional, Albania, M., additional, Arora, S., additional, Shi, Y., additional, Abudayah, A., additional, Almekhlafi, G., additional, Al Amodi, E., additional, Al Samarrai, S., additional, Badawi, M., additional, Caba, R. Cubio, additional, Elffaki, O., additional, Mandourah, Y., additional, Valerio, J., additional, Joyce, C., additional, Meyer, J., additional, Saylor, E., additional, Venkatesh, B., additional, Venz, E., additional, Walsham, J., additional, Wetzig, K., additional, Khoo, T. M., additional, Liew, J. E. S., additional, Sakthi, A. N., additional, Zulkurnain, A., additional, Bamford, A., additional, Bergin, C., additional, Carrera, R., additional, Cooper, L., additional, Despy, L., additional, Harkett, S., additional, Mee, L., additional, Reeves, E., additional, Snelson, C., additional, Spruce, E., additional, Cooper, G., additional, Hodgson, R., additional, Pearson, D., additional, Rosbergen, M., additional, Ali, M. N., additional, Bahar, N. I., additional, Ismail, A., additional, Ismail, W. N. W., additional, Samat, N. M., additional, Piah, N. S. M., additional, Rahman, R. Abd, additional, Duroux, M., additional, Ratcliffe, M., additional, Warhurst, T., additional, Buehner, U., additional, Williams, E., additional, Jacques, N., additional, Keating, L., additional, Macgill, S., additional, Tamang, K. L., additional, Tolan, N., additional, Walden, A., additional, Bower, R., additional, Cranshaw, J., additional, Molloy, K., additional, Pitts, S., additional, Butler, J., additional, Dunlop, R., additional, Fourie, C., additional, Jarrett, P., additional, Lassig-Smith, M., additional, Livermore, A., additional, O’Donoghue, S., additional, Reade, M., additional, Starr, T., additional, Stuart, J., additional, Campbell, L., additional, Phillips, M., additional, Stephens, D., additional, Thomas, J., additional, Cooper, D., additional, McAllister, R., additional, Andrew, G., additional, Barclay, L., additional, Dawson, H., additional, Griffith, D. M., additional, Hope, D., additional, Wojcik, G., additional, McCulloch, C., additional, Paterson, R., additional, Ascough, L., additional, Paisley, C., additional, Patrick-Heselton, J., additional, Shaw, D., additional, Waugh, V., additional, Williams, K., additional, Welters, I., additional, Barge, D., additional, Jordan, A., additional, MacIsaac, C., additional, Rechnitzer, T., additional, Bass, F., additional, Gatward, J., additional, Hammond, N., additional, Janin, P., additional, Stedman, W., additional, Yarad, E., additional, Razak, N. A., additional, Dzulkipli, N., additional, Jong, S. L., additional, Asen, K., additional, Voon, W. L., additional, Liew, S., additional, Ball, J., additional, Barnes, V., additional, Dalton, C., additional, Farnell-Ward, S., additional, Farrah, H., additional, Maher, K., additional, Mellinghoff, J., additional, Ryan, C., additional, Shirley, P., additional, Conlon, L., additional, Glover, A., additional, Martin-Loeches, I., additional, O’Toole, E., additional, Ewan, J., additional, Ferrier, J., additional, Litton, E., additional, Webb, S. A., additional, Berry, W., additional, Blanco Alonso, U., additional, Bociek, A., additional, Campos, S., additional, Jawara, S., additional, Hanks, F., additional, Kelly, A., additional, Lei, K., additional, McKenzie, C., additional, Ostermann, M., additional, Wan, R., additional, Al-Soufi, S., additional, Leow, S., additional, McCann, K., additional, Reynolds, C., additional, Brickell, K., additional, Fahey, C., additional, Hays, L., additional, Hyde, N., additional, Nichol, A., additional, Ryan, D., additional, Brailsford, J., additional, Buckley, A., additional, Forbes, L., additional, Maguire, T., additional, Moore, J., additional, Murray, L., additional, Ghosh, A., additional, Park, M., additional, Said, S., additional, Visser, A., additional, Abidin, H. Z., additional, Ali, S., additional, Hassan, M. H., additional, Omar, S. C., additional, Shukeri, W. F. W., additional, Brealey, D., additional, Bercades, G., additional, Blackburn, E., additional, Macallum, N., additional, Macklin, A., additional, Ryu, J. H., additional, Tam, K., additional, Smyth, D., additional, Arif, A., additional, Bassford, C., additional, Morgan, C., additional, Swann, C., additional, Ward, G., additional, Wild, L., additional, Bone, A., additional, Elderkin, T., additional, Green, D., additional, Sach, D., additional, Salerno, T., additional, Simpson, N., additional, Brohi, F., additional, Clark, M., additional, Williams, L., additional, Brooks, J., additional, Cocks, E., additional, Cole, J., additional, Curtin, J., additional, Davies, R., additional, Hill, H., additional, Morgan, M., additional, Palmer, N., additional, Whitton, C., additional, Wise, M., additional, Baskaran, P., additional, Hasan, M. S., additional, Tham, L. Y., additional, Sol Cruz, R., additional, Dinsdale, D., additional, Edney, S., additional, Firkin, C., additional, FitzJohn, F., additional, Hill, G., additional, Hunt, A., additional, Hurford, S., additional, Jones, G., additional, Judd, H., additional, Latimer-Bell, C., additional, Lawrence, C., additional, Lesona, E., additional, Navarra, L., additional, Robertson, Y., additional, Smellie, H., additional, Vucago, A. M., additional, Young, P., additional, Clark, P., additional, Kong, J., additional, Ho, J., additional, Nayyar, V., additional, and Skelly, C., additional

Published
2023
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6. Hallmarks of pluripotency

Author

De Los Angeles, Alejandro, Ferrari, Francesco, Xi, Ruibin, Fujiwara, Yuko, Benvenisty, Nissim, Deng, Hongkui, Hochedlinger, Konrad, Jaenisch, Rudolf, Lee, Soohyun, Leitch, Harry G., Lensch, M. William, Lujan, Ernesto, Pei, Duanqing, Rossant, Janet, Wernig, Marius, Park, Peter J., and Daley, George Q.

Published
2015
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11. Early sedation with dexmedetomidine in ventilated critically ill patients and heterogeneity of treatment effect in the SPICE III randomised controlled trial.

Author

Abidin H.Z., Hassan M.H., Omar S.C., Shukeri W.F.W., Brealey D., Bercades G., Blackburn E., Macallum N., Macklin A., Ryu J.H., Tam K., Smyth D., Arif A., Bassford C., Morgan C., Swann C., Ward G., Wild L., Bone A., Elderkin T., Green D., Sach D., Salerno T., Simpson N., Brohi F., Clark M., Williams L., Brooks J., Cocks E., Cole J., Curtin J., Davies R., Hill H., Morgan M., Palmer N., Whitton C., Wise M., Baskaran P., Hasan M.S., Tham L.Y., Cruz R.S., Dinsdale D., Edney S., Firkin C., FitzJohn F., Hill G., Hunt A., Hurford S., Jones G., Judd H., Latimer-Bell C., Lawrence C., Lesona E., Navarra L., Robertson Y., Smellie H., Vucago A.M., Young P., Dawson H., Griffith D.M., Paterson R., Clark P., Kong J., Ho J., Nayyar V., Skelly C., Shehabi Y., Serpa Neto A., Howe B.D., Arabi Y.M., Bass F.E., Kadiman S.B., McArthur C.J., Reade M.C., Seppelt I.M., Wise M.P., Mashonganyika C., McKee H., Tonks A., Donnelly A., Hemmings N., O'Kane S., Blakemore A., Butler M., Cowdrey K., Dalton J., Gilder E., Long S., McCarthy L., McGuinness S., Parke R., Chen Y., McArthur C., McConnochie R., Newby L., Bellomo R., Eastwood G., Peck L., Young H., Boschert C., Edington J., Fletcher J., Nand K., Raza A., Sara T., Bennett-Britton J., Bewley J., Bodenham V., Cole L., Driver K., Grimmer L., Howie L., Searles C., Sweet K., Webster D., van Berkel A., Connor H., Dennett J., van Der Graaff M., Henderson S., Mehrtens J., Miller K., Minto E., Morris A., Noble S., Parker K., Hart N., Shepherd K., Vij S., Dickson S., Elloway E., Ferguson C., Jackson R., MacNaughton P., Marner M., Squire R., Waddy S., Wafer P., Welbourne J., Ashcroft P., Chambler D., Dukes S., Harris A., Horton S., Sharpe S., Williams P., Williams S., Bailey M., Blazquez E., France D., Hutchison R., Comadira G., Gough M., Tallott M., Bastick M., Cameron R., Donovan S., Gaur A., Gregory R., Naumoff J., Turner E., White M., Au K.F.J., Fratzia J., Treloar S., Lim C.H., Maseeda Y., Tan A.P., Tang C.L., Yong C.Y., Akaltan M., Berger S., Blaser D., Fazlija L., Jong M.L., Lensch M., Ludwig R., Merz T., Nettelbeck K., Roth M., Schafer M., Takala J., Wehr A., Zacharias D., Amran R., Ashraf H.N., Azmi N., Basri N., Burhanuddin H., Hadinata Y., Hamdan A., Kadiman S., Rashid A.I.Y.M., Sabran I.N., Sulaiman S., Zabidi I.N., Al-Dawood A., Aljuaid M., Al Anizi H., Al Saeedi A., Arabi Y., Dbsawy M., Deeb A., Hegazy M., Magdi I., Corcoran E., Finney C., Dumlao L.A., Bassam R., Hassan M.A., Naseem N., Al-Kurdi M.H., Al-Harthy A.M., Bernard S., Sebafundi L., Serban C., Lim S.K., Mazidah N., Saidin N., Sjamsuddin N., Tan I.T.A., Zabidi N., Brain M., Mineall S., Kanhere M., Soar N., Kadir N.A., Abdullah N.H., Awang R., Emperan Z., Husin N.S., Ismail N.I., Ismail S.Z., Khadzali F.N.A.M., Norddin M.F., Aguila J., Bold C., Clatworthy B., Dias A., Hogan C., Kazemi A., Lai V., Song R., Williams A., Bhatia D., Bulfin L., Elliot S., Galt P., Lavrans K., Ritchie P., Wang A., Gresham R., Lowrey J., Masters K., Palejs P., Seppelt I., Symonds F., Weisbrodt L., Whitehead C., Babio-Galan M., Calder V., Clement I., Harrison A., McCullagh I., Scott C., Bevan R., Caniba S., Hacking D., Maher L., Azzolini M.L., Beccaria P., Colombo S., Landoni G., Leggieri C., Luca C., Mamo D., Moizo E., Monti G., Mucci M., Zangrillo A., Albania M., Arora S., Shi Y., Abudayah A., Almekhlafi G., Al Amodi E., Al Samarrai S., Badawi M., Caba R.C., Elffaki O., Mandourah Y., Valerio J., Joyce C., Meyer J., Saylor E., Venkatesh B., Venz E., Walsham J., Wetzig K., Clarey E., Harris C., Hopkins P., Noble H., Thompson L., Williams T., Khoo T.M., Liew J.E.S., Sakthi A.N., Zulkurnain A., Bamford A., Bergin C., Carrera R., Cooper L., Despy L., Ellis K., Harkett S., Mee L., Reeves E., Snelson C., Spruce E., Cooper G., Hodgson R., Pearson D., Rosbergen M., Ali M.N., Bahar N.I., Ismail A., Ismail W.N.W., Samat N.M., Piah N.S.M., Rahman R.A., Duroux M., Ratcliffe M., Warhurst T., Buehner U., Williams E., Jacques N., Keating L., Macgill S., Tamang K.L., Tolan N., Walden A., Bower R., Cranshaw J., Molloy K., Pitts S., Butler J., Dunlop R., Fourie C., Jarrett P., Lassig-Smith M., Livermore A., O'Donoghue S., Reade M., Starr T., Stuart J., Campbell L., Phillips M., Stephens D., Thomas J., Cooper D., McAllister R., Andrew G., Barclay L., Hope D., Wojcik G., McCulloch C., Ascough L., Paisley C., Patrick-Heselton J., Shaw D., Waugh V., Williams K., Welters I., Barge D., Jordan A., MacIsaac C., Rechnitzer T., Bass F., Gatward J., Hammond N., Janin P., O'Connor A., Stedman W., Yarad E., Razak N.A., Dzulkipli N., Jong S.L., Asen K., Voon W.L., Liew S., Ball J., Barnes V., Dalton C., Farnell-Ward S., Farrah H., Maher K., Mellinghoff J., Ryan C., Shirley P., Conlon L., Glover A., Martin-Loeches I., O'Toole E., Ewan J., Ferrier J., Litton E., Webb S.A., Berry W., Alonso U.B., Bociek A., Campos S., Jawara S., Hanks F., Kelly A., Lei K., McKenzie C., Ostermann M., Wan R., Al-Soufi S., Leow S., McCann K., Reynolds C., Brickell K., Fahey C., Hays L., Hyde N., Nichol A., Ryan D., Brailsford J., Buckley A., Forbes L., Maguire T., Moore J., Murray L., Ghosh A., Park M., Said S., Smith J., Visser A., Ali S., Abidin H.Z., Hassan M.H., Omar S.C., Shukeri W.F.W., Brealey D., Bercades G., Blackburn E., Macallum N., Macklin A., Ryu J.H., Tam K., Smyth D., Arif A., Bassford C., Morgan C., Swann C., Ward G., Wild L., Bone A., Elderkin T., Green D., Sach D., Salerno T., Simpson N., Brohi F., Clark M., Williams L., Brooks J., Cocks E., Cole J., Curtin J., Davies R., Hill H., Morgan M., Palmer N., Whitton C., Wise M., Baskaran P., Hasan M.S., Tham L.Y., Cruz R.S., Dinsdale D., Edney S., Firkin C., FitzJohn F., Hill G., Hunt A., Hurford S., Jones G., Judd H., Latimer-Bell C., Lawrence C., Lesona E., Navarra L., Robertson Y., Smellie H., Vucago A.M., Young P., Dawson H., Griffith D.M., Paterson R., Clark P., Kong J., Ho J., Nayyar V., Skelly C., Shehabi Y., Serpa Neto A., Howe B.D., Arabi Y.M., Bass F.E., Kadiman S.B., McArthur C.J., Reade M.C., Seppelt I.M., Wise M.P., Mashonganyika C., McKee H., Tonks A., Donnelly A., Hemmings N., O'Kane S., Blakemore A., Butler M., Cowdrey K., Dalton J., Gilder E., Long S., McCarthy L., McGuinness S., Parke R., Chen Y., McArthur C., McConnochie R., Newby L., Bellomo R., Eastwood G., Peck L., Young H., Boschert C., Edington J., Fletcher J., Nand K., Raza A., Sara T., Bennett-Britton J., Bewley J., Bodenham V., Cole L., Driver K., Grimmer L., Howie L., Searles C., Sweet K., Webster D., van Berkel A., Connor H., Dennett J., van Der Graaff M., Henderson S., Mehrtens J., Miller K., Minto E., Morris A., Noble S., Parker K., Hart N., Shepherd K., Vij S., Dickson S., Elloway E., Ferguson C., Jackson R., MacNaughton P., Marner M., Squire R., Waddy S., Wafer P., Welbourne J., Ashcroft P., Chambler D., Dukes S., Harris A., Horton S., Sharpe S., Williams P., Williams S., Bailey M., Blazquez E., France D., Hutchison R., Comadira G., Gough M., Tallott M., Bastick M., Cameron R., Donovan S., Gaur A., Gregory R., Naumoff J., Turner E., White M., Au K.F.J., Fratzia J., Treloar S., Lim C.H., Maseeda Y., Tan A.P., Tang C.L., Yong C.Y., Akaltan M., Berger S., Blaser D., Fazlija L., Jong M.L., Lensch M., Ludwig R., Merz T., Nettelbeck K., Roth M., Schafer M., Takala J., Wehr A., Zacharias D., Amran R., Ashraf H.N., Azmi N., Basri N., Burhanuddin H., Hadinata Y., Hamdan A., Kadiman S., Rashid A.I.Y.M., Sabran I.N., Sulaiman S., Zabidi I.N., Al-Dawood A., Aljuaid M., Al Anizi H., Al Saeedi A., Arabi Y., Dbsawy M., Deeb A., Hegazy M., Magdi I., Corcoran E., Finney C., Dumlao L.A., Bassam R., Hassan M.A., Naseem N., Al-Kurdi M.H., Al-Harthy A.M., Bernard S., Sebafundi L., Serban C., Lim S.K., Mazidah N., Saidin N., Sjamsuddin N., Tan I.T.A., Zabidi N., Brain M., Mineall S., Kanhere M., Soar N., Kadir N.A., Abdullah N.H., Awang R., Emperan Z., Husin N.S., Ismail N.I., Ismail S.Z., Khadzali F.N.A.M., Norddin M.F., Aguila J., Bold C., Clatworthy B., Dias A., Hogan C., Kazemi A., Lai V., Song R., Williams A., Bhatia D., Bulfin L., Elliot S., Galt P., Lavrans K., Ritchie P., Wang A., Gresham R., Lowrey J., Masters K., Palejs P., Seppelt I., Symonds F., Weisbrodt L., Whitehead C., Babio-Galan M., Calder V., Clement I., Harrison A., McCullagh I., Scott C., Bevan R., Caniba S., Hacking D., Maher L., Azzolini M.L., Beccaria P., Colombo S., Landoni G., Leggieri C., Luca C., Mamo D., Moizo E., Monti G., Mucci M., Zangrillo A., Albania M., Arora S., Shi Y., Abudayah A., Almekhlafi G., Al Amodi E., Al Samarrai S., Badawi M., Caba R.C., Elffaki O., Mandourah Y., Valerio J., Joyce C., Meyer J., Saylor E., Venkatesh B., Venz E., Walsham J., Wetzig K., Clarey E., Harris C., Hopkins P., Noble H., Thompson L., Williams T., Khoo T.M., Liew J.E.S., Sakthi A.N., Zulkurnain A., Bamford A., Bergin C., Carrera R., Cooper L., Despy L., Ellis K., Harkett S., Mee L., Reeves E., Snelson C., Spruce E., Cooper G., Hodgson R., Pearson D., Rosbergen M., Ali M.N., Bahar N.I., Ismail A., Ismail W.N.W., Samat N.M., Piah N.S.M., Rahman R.A., Duroux M., Ratcliffe M., Warhurst T., Buehner U., Williams E., Jacques N., Keating L., Macgill S., Tamang K.L., Tolan N., Walden A., Bower R., Cranshaw J., Molloy K., Pitts S., Butler J., Dunlop R., Fourie C., Jarrett P., Lassig-Smith M., Livermore A., O'Donoghue S., Reade M., Starr T., Stuart J., Campbell L., Phillips M., Stephens D., Thomas J., Cooper D., McAllister R., Andrew G., Barclay L., Hope D., Wojcik G., McCulloch C., Ascough L., Paisley C., Patrick-Heselton J., Shaw D., Waugh V., Williams K., Welters I., Barge D., Jordan A., MacIsaac C., Rechnitzer T., Bass F., Gatward J., Hammond N., Janin P., O'Connor A., Stedman W., Yarad E., Razak N.A., Dzulkipli N., Jong S.L., Asen K., Voon W.L., Liew S., Ball J., Barnes V., Dalton C., Farnell-Ward S., Farrah H., Maher K., Mellinghoff J., Ryan C., Shirley P., Conlon L., Glover A., Martin-Loeches I., O'Toole E., Ewan J., Ferrier J., Litton E., Webb S.A., Berry W., Alonso U.B., Bociek A., Campos S., Jawara S., Hanks F., Kelly A., Lei K., McKenzie C., Ostermann M., Wan R., Al-Soufi S., Leow S., McCann K., Reynolds C., Brickell K., Fahey C., Hays L., Hyde N., Nichol A., Ryan D., Brailsford J., Buckley A., Forbes L., Maguire T., Moore J., Murray L., Ghosh A., Park M., Said S., Smith J., Visser A., and Ali S.

Abstract

Purpose: To quantify potential heterogeneity of treatment effect (HTE), of early sedation with dexmedetomidine (DEX) compared with usual care, and identify patients who have a high probability of lower or higher 90-day mortality according to age, and other identified clusters. Method(s): Bayesian analysis of 3904 critically ill adult patients expected to receive invasive ventilation > 24 h and enrolled in a multinational randomized controlled trial comparing early DEX with usual care sedation. Result(s): HTE was assessed according to age and clusters (based on 12 baseline characteristics) using a Bayesian hierarchical models. DEX was associated with lower 90-day mortality compared to usual care in patients > 65 years (odds ratio [OR], 0.83 [95% credible interval [CrI] 0.68-1.00], with 97.7% probability of reduced mortality across broad categories of illness severity. Conversely, the probability of increased mortality in patients = 65 years was 98.5% (OR 1.26 [95% CrI 1.02-1.56]. Two clusters were identified: cluster 1 (976 patients) mostly operative, and cluster 2 (2346 patients), predominantly non-operative. There was a greater probability of benefit with DEX in cluster 1 (OR 0.86 [95% CrI 0.65-1.14]) across broad categories of age, with 86.4% probability that DEX is more beneficial in cluster 1 than cluster 2. Conclusion(s): In critically ill mechanically ventilated patients, early sedation with dexmedetomidine exhibited a high probability of reduced 90-day mortality in older patients regardless of operative or non-operative cluster status. Conversely, a high probability of increased 90-day mortality was observed in younger patients of non-operative status. Further studies are needed to confirm these findings.Copyright © 2021, Crown.

Published
2021

14. Biomechanical forces promote embryonic haematopoiesis

Author

Adamo, Luigi, Naveiras, Olaia, Wenzel, Pamela L., McKinney-Freeman, Shannon, Mack, Peter J., Gracia-Sancho, Jorge, Suchy-Dicey, Astrid, Yoshimoto, Momoko, Lensch, M. William, Yoder, Mervin C., Garcia-Cardena, Guillermo, and Daley, George Q.

Subjects
Hematopoiesis -- Research, Embryonic development -- Research, Biomechanics -- Influence -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation, Influence, Research
Abstract

Biomechanical forces are emerging as critical regulators of embryogenesis, particularly in the developing cardiovascular system (1,2). After initiation of the heartbeat in vertebrates, cells lining the ventral aspect of the dorsal aorta, the placental vessels, and the umbilical and vitelline arteries initiate expression of the transcription factor Runx1 (refs 3-5), a master regulator of haematopoiesis, and give rise to haematopoietic cells (4). It remains unknown whether the biomechanical forces imposed on the vascular wall at this developmental stage act as a determinant of haematopoietic potential (6). Here, using mouse embryonic stem cells differentiated in vitro, we show that fluid shear stress increases the expression of Runx1 in [CD411.sup.+]c-[Kit.sup.+] haematopoietic progenitor cells (7), concomitantly augmenting their haematopoietic colony-forming potential. Moreover, we find that shear stress increases haematopoietic colony-forming potential and expression of haematopoietic markers in the para-aortic splanchnopleura/aorta-gonads-mesonephros of mouse embryos and that abrogation of nitric oxide, a mediator of shear-stress-induced signalling (8), compromises haematopoietic potential in vitro and in vivo. Collectively, these data reveal a critical role for biomechanical forces in haematopoietic development., In the mouse, the first haemogenic areas appear in the yolk sac starting at day 7.5 of development (E7.5) (9). After the establishment of circulation and the onset of vascular [...]

Published
2009

15. Down's syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR1

Author

Baek, Kwan-Hyuck, Zaslavsky, Alexander, Lynch, Ryan C., Britt, Carmella, Okada, Yoshiaki, Siarey, Richard J., Lensch, M. William, Park, In-Hyun, Yoon, Sam S., Minami, Takashi, Korenberg, Julie R., Folkman, Judah, Daley, George Q., Aird, William C., Galdzicki, Zygmunt, and Ryeom, Sandra

Subjects
Leukemia -- Risk factors -- Genetic aspects -- Drug therapy, Calcineurin -- Physiological aspects -- Genetic aspects -- Chemical properties, Down syndrome -- Drug therapy -- Causes of -- Risk factors -- Genetic aspects, Tumor suppressor genes -- Distribution -- Chemical properties -- Physiological aspects -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation, Company distribution practices, Drug therapy, Distribution, Physiological aspects, Chemical properties, Genetic aspects, Risk factors, Causes of
Abstract

The incidence of many cancer types is significantly reduced in individuals with Down's syndrome (1-4), and it is thought that this broad cancer protection is conferred by the increased expression of one or more of the 231 supernumerary genes on the extra copy of chromosome 21. One such gene is Down's syndrome candidate region-1 (DSCR1, also known as RCANI), which encodes a protein that suppresses vascular endothelial growth factor (VEGF)-mediated angiogenic signalling by the calcineurin pathways (5-10). Here we show that DSCR1 is increased in Down's syndrome tissues and in a mouse model of Down's syndrome. Furthermore, we show that the modest increase in expression afforded by a single extra transgenic copy of Dscr1 is sufficient to confer significant suppression of tumour growth in mice, and that such resistance is a consequence of a deficit in tumour angiogenesis arising from suppression of the calcineurin pathway. We also provide evidence that attenuation of calcineurin activity by DSCR1, together with another chromosome 21 gene Dyrkla, may be sufficient to markedly diminish angiogenesis. These data provide a mechanism for the reduced cancer incidence in Down's syndrome and identify the calcineurin signalling pathway, and its regulators DSCR1 and DYRKIA, as potential therapeutic targets in cancers arising in all individuals., Down's syndrome is the most common genetic cause of mental retardation in humans, occurring in 1 out of 700 live births. Epidemiological studies suggest that although individuals with Down's syndrome [...]

Published
2009

16. Reprogramming of human somatic cells to pluripotency with defined factors

Author

Park, In-Hyun, Zhao, Rui, West, Jason A., Yabuuchi, Akiko, Huo, Hongguang, Ince, Tan A., Lerou, Paul H., Lensch, M. William, and Daley, George Q.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Pluripotency pertains to the cells of early embryos that can generate all of the tissues in the organism. Embryonic stem cells are embryo-derived cell lines that retain pluripotency and represent [...]

Published
2008

23. DNA deletion associated with hereditary neuropathy withh liability to pressure palsies

Author

Chance, Phillip F., Alderson, Mary Kathryn, Leppig, Kathleen A., Lensch, M. William, Matsunami, Norisada, Smith, Brooke, Swanson, Phillip D., Odelberg, Shannon J., Disteche, Christine M., and Bird, Thomas D.

Subjects
Polyneuropathies -- Genetic aspects, Charcot-Marie-Tooth disease -- Genetic aspects, Chromosome mapping -- Research, Biological sciences
Abstract

The chromosomal aberration associated with hereditary neuropathy with liability to pressure palsies (HNPP) was identified. Using DNA markers developed from Charcot-Marie-Tooth disease type 1 (CMT1), HNPP was attributed to a large deletion in 17p11.2 spanning 1.5 Mb and including all markers mapped to the duplicated region associated with CMT1A. It is proposed that HNPP and CMT1 are the products of unequal crossing over during meiosis, producing a deleted and duplicated region in chromosome 17, respectively.

Published
1993

25. Looking into the future of cell-based therapy

Author

Lensch, M. William and West, Jason A.

Subjects
Regenerative medicine -- Forecasts and trends, Nuclear reprogramming -- Forecasts and trends, Embryonic stem cells -- Genetic aspects, Stem cell research -- Forecasts and trends, Stem cells -- Transplantation, Stem cells -- Forecasts and trends, Market trend/market analysis, Health
Published
2008

26. Broader Implications of Defining Standards for the Pluripotency of iPSCs

Author

Whitehead Institute for Biomedical Research, Jaenisch, Rudolf, Daley, George Q., Lensch, M. William, Meissner, Alexander, Plath, Kathrin, Yamanaka, Shinya, Whitehead Institute for Biomedical Research, Jaenisch, Rudolf, Daley, George Q., Lensch, M. William, Meissner, Alexander, Plath, Kathrin, and Yamanaka, Shinya

Abstract

We read with great interest the excellent review by Maherali and Hochedlinger (2008) that recommends standards for characterization of pluripotent stem cell lines, especially the many new lines being generated using factor-based reprogramming techniques (induced pluripotent stem cells, or iPSCs). Of note was the suggestion that iPSCs should be assessed for “functional differentiation through the highest-stringency test acceptable.” For murine iPSCs, this means germline transmission following blastocyst chimerism, and for human iPSCs this means assessment of teratoma pathology. Given the fast pace of discovery in the field, the value and relevance of time-consuming characterization of cell lines are bound to be debated. We'd like to highlight what's at risk when the pressure for rapid publication erodes the imperative for applying rigorous and uniform standards before assigning the label “iPSC” to novel cell lines.

Published
2015

27. Human galectin-3 (Mac-2 antigen): Defining molecular switches of affinity to natural glycoproteins, structural and dynamic aspects of glycan binding by flexible ligand docking and putative regulatory sequences in the proximal promoter region

Author

Krzeminski, M.N., Singh, T., André, S., Lensch, M., Wu, A.M., Bonvin, A.M.J.J., Gabius, H.-J., NMR Spectroscopy, Sub NMR Spectroscopy, NMR Spectroscopy, and Sub NMR Spectroscopy

Subjects
Models, Molecular, Glycan, Glycoconjugate, In silico, Galectin 3, Molecular Sequence Data, Biophysics, Oligosaccharides, Computational biology, Regulatory Sequences, Nucleic Acid, Ligands, Biochemistry, Binding, Competitive, 03 medical and health sciences, 0302 clinical medicine, Polysaccharides, Taverne, Humans, Avidity, Promoter Regions, Genetic, Molecular Biology, 030304 developmental biology, Glycoproteins, chemistry.chemical_classification, 0303 health sciences, Binding Sites, biology, Base Sequence, Effector, Monosaccharides, Computational Biology, Hydrogen Bonding, Kinetics, chemistry, Carbohydrate Sequence, Docking (molecular), Regulatory sequence, 030220 oncology & carcinogenesis, biology.protein, Glycoprotein, Protein Binding
Abstract

Background Human galectin-3 (Mac-2 antigen) is a cell-type-specific multifunctional effector owing to selective binding of distinct cell-surface glycoconjugates harboring β-galactosides. The structural basis underlying the apparent preferences for distinct glycoproteins and for expression is so far unknown. Methods We strategically combined solid-phase assays on 43 natural glycoproteins with a new statistical approach to fully flexible computational docking and also processed the proximal promoter region in silico. Results The degree of branching in N-glycans and clustering of core 1 O-glycans are positive modulators for avidity. Sialylation of N-glycans in α2–6 linkage and of core 1 O-glycans in α2–3 linkage along with core 2 branching was an unfavorable factor, despite the presence of suited glycans in the vicinity. The lectin–ligand contact profile was scrutinized for six natural di- and tetrasaccharides enabling a statistical grading by analyzing flexible docking trajectories. The computational analysis of the proximal promoter region delineated putative sites for Lmo2/c-Ets-1 binding and new sites with potential for RUNX binding. General significance These results identify new features of glycan selectivity and ligand contact by combining solid-phase assays with in silico work as well as of reactivity potential of the promoter.

Published
2011
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28. Erratum: Corrigendum: Hallmarks of pluripotency

Author

De Los Angeles, Alejandro, primary, Ferrari, Francesco, additional, Xi, Ruibin, additional, Fujiwara, Yuko, additional, Benvenisty, Nissim, additional, Deng, Hongkui, additional, Hochedlinger, Konrad, additional, Jaenisch, Rudolf, additional, Lee, Soohyun, additional, Leitch, Harry G., additional, Lensch, M. William, additional, Lujan, Ernesto, additional, Pei, Duanqing, additional, Rossant, Janet, additional, Wernig, Marius, additional, Park, Peter J., additional, and Daley, George Q., additional

Published
2015
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29. Galectin-7, will the lectinrsquos activity establish clinical correlations in head and neck squamous cell and basal cell carcinomas?

Author

Câda, Z., Chovanec, M., Smetana, K. Jr., Betka, J., Lacina, L., Plzák, J., Kodet, R., Stork, J., Lensch, M., Kaltner, H., André, S., and Gabius, H.J.

Subjects
616 - Patología. Medicina clínica. Oncología, Carcinoma, Galectin
Abstract

The human lectin galectin-7 (Gal-7; p53- induced gene-1) has anti- and pro-malignant features in different in vitro models. We tried to clarify relation of its expression to cellular and clinical parameters in head and neck squamous and basal cell carcinomas. Using a non-cross-reactive antibody, immunohistochemical staining in squamous cell epithelia (epidermis, epithelium of oropharynx and larynx) (n = 57), squamous cell carcinomas (n = 47) and lymph node metastases (n = 25), as well as basal cell carcinomas (n = 10) were studied. This monitoring was flanked by processing to assess the level of differentiation (cytokeratins 10 and 14), proliferation (Ki67) and basal lamina formation (collagen IV). The results were correlated with clinical and pathological findings (grading, TNM-staging, extracapsular spread, angio- and lymphangioinvasion, perineural invasion, recurrence and survival). Gal-7 resides in all layers of epithelia with cytoplasmic and nuclear localization in normal specimens. Basal cell carcinomas were devoid of the Gal-7 respective signal. Squamous cell carcinomas were positive, presenting different staining profiles. Intense staining was predominantly found in squamous cell cancers with high degrees of differentiation and keratinization. Fittingly, poor level of differentiation (P = 0.0009), absence of keratinization (P = 0.0105) and significant discontinuity or absence of collagen IV expression in the peritumoral basal lamina (P = 0.0024). was found in Gal-7-negative tumors. Gal-7 presence was not related to gender, primary tumor site, T-stage, Nstage, clinical stage, extracapsular spread, angio- and lymphangioinvasion, perineural spread or treatment outcome at a statistically significant level. Immunohistochemical analysis revealed a positive correlation for differentiation and keratinization to Gal-7 presence in squamous cell carcinomas. Absence of Gal-7 expression was detected in basal cell carcinomas. These clinical data delineate Gal-7 influence on differentiation in vivo, without evidence for a role in dissemination reported for lymphoma.

Published
2009

30. Human galectin-2: expression profiling by RT-PCR/immunohistochemistry and its introduction as a histochemical tool for ligand localization

Author

Saal I, Nagy N, Lensch M, Lohr M, Jc, Manning, Decaestecker C, Sabine André, Kiss R, Salmon I, and Hj, Gabius

Subjects
Inflammation, Galectin 1, Galectin 2, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, 6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncología [CDU], Gallbladder, Ligands, Immunohistochemistry, Antibodies, Organ Specificity, Lectins, Humans, Biliary tract, RNA, Messenger, Biomarkers
Abstract

Sugar-encoded information of glycoconjugates is translated into cellular responses by endogenous lectins. Galectins stand out against other lectin families due to their wide range of functions including cell adhesion, tissue invasion or growth regulation exerted at extracellular, membrane, cytoplasmic and nuclear sites. This remarkable versatility warrants close scrutiny of their emerging network, in this study with focus on homodimeric human galectin-2. We first detected presence of specific mRNA in various tissue types by processing post mortem and surgical specimens by RT-PCR protocols. Overlap of gene expression was noted with proto-type galectins-1 and -7 and also family members from the other two subgroups. To monitor expression on the level of protein a polyclonal anti-galectin-2 antibody was raised. Immunopositivity was semi-quantitatively assessed in sections of 209 human samples establishing an array both of normal tissues and samples with inflammation or benign/malignant growth. In general, positivity was predominantly epithelial without restriction of staining to certain tissue types, as fittingly indicated by our RT-PCR analysis. Staining was not limited to the cytoplasm but also included nuclear sites. To examine the suitability of the labeled lectin as a histochemical probe we biotinylated galectin-2 under activity-preserving conditions and introduced it to tissue profiling. Specific cytoplasmic staining proved the validity of the concept. Our results encourage systematic histopathologic studies by immuno- and lectin histochemistry, especially by adding galectin-2 as study object to galectin fingerprinting which has already yielded prognostic information on galectins-1, -3, -4 and -8 and hereby contributed to define functional overlap/divergence in this lectin family.

Published
2005

31. Reprogramming of T Cells from Human Peripheral Blood

Author

Loh, Yuin-Han, Hartung, Odelya, Li, Hu, Guo, Chunguang, Sahalie, Julie M., Manos, Philip D., Urbach, Achia, Heffner, Garrett C., Grskovic, Marica, Vigneault, Francois, Lensch, M. William, Park, In-Hyun, Agarwal, Suneet, Church, George M., Collins, James J., Irion, Stefan, and Daley, George Q.

Published
2010
Full Text
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33. Adhesion/growth-regulatory galectins: insights into their ligand selectivity using natural glycoproteins and glycotopes

Author

Wu, A.M., Singh, T., Liu, J.-H., André, S., Lensch, M., Siebert, H.-C., Krzeminski, M.N., Bonvin, A.M.J.J., Kaltner, H., Wu, J.H., Wu, A.M., Singh, T., Liu, J.-H., André, S., Lensch, M., Siebert, H.-C., Krzeminski, M.N., Bonvin, A.M.J.J., Kaltner, H., and Wu, J.H.

Abstract

“Biochemistry text books commonly make it appear that it is a foregone conclusion that the hardware of biological information storage and transfer is confined to nucleotides and amino acids, the letters of the genetic code. However, the remarkable talents of a third class of biomolecules are often overlooked” [1]. This statement from a recent review guides the readers to look at and fully appreciate the chemical/lectinochemical characteristics of carbohydrates that underlie the concept of the sugar code [2].

Published
2011

34. Human galectin-3 (Mac-2 antigen): Defining molecular switches of affinity to natural glycoproteins, structural and dynamic aspects of glycan binding by flexible ligand docking and putative regulatory sequences in the proximal promoter region

Author

NMR Spectroscopy, Sub NMR Spectroscopy, Krzeminski, M.N., Singh, T., André, S., Lensch, M., Wu, A.M., Bonvin, A.M.J.J., Gabius, H.-J., NMR Spectroscopy, Sub NMR Spectroscopy, Krzeminski, M.N., Singh, T., André, S., Lensch, M., Wu, A.M., Bonvin, A.M.J.J., and Gabius, H.-J.

Published
2011

36. Human galectin-2: expression profiling by RT-PCR/immunohistochemistry and its introduction as a histochemical tool for ligand localization.

Author

Saal, Isabelle, Nagy, Nathalie, Lensch, M, Lohr, M, Manning, J C, Decaestecker, Christine, André, Sabine, Kiss, Robert, Salmon, Isabelle, Gabius, Hans-Joachim, Saal, Isabelle, Nagy, Nathalie, Lensch, M, Lohr, M, Manning, J C, Decaestecker, Christine, André, Sabine, Kiss, Robert, Salmon, Isabelle, and Gabius, Hans-Joachim

Abstract

Sugar-encoded information of glyco-conjugates is translated into cellular responses by endogenous lectins. Galectins stand out against other lectin families due to their wide range of functions including cell adhesion, tissue invasion or growth regulation exerted at extracellular, membrane, cytoplasmic and nuclear sites. This remarkable versatility warrants close scrutiny of their emerging network, in this study with focus on homodimeric human galectin-2. We first detected presence of specific mRNA in various tissue types by processing post mortem and surgical specimens by RT-PCR protocols. Overlap of gene expression was noted with proto-type galectins-1 and -7 and also family members from the other two subgroups. To monitor expression on the level of protein a polyclonal anti-galectin-2 antibody was raised. Immunopositivity was semi-quantitatively assessed in sections of 209 human samples establishing an array both of normal tissues and samples with inflammation or benign/malignant growth. In general, positivity was predominantly epithelial without restriction of staining to certain tissue types, as fittingly indicated by our RT-PCR analysis. Staining was not limited to the cytoplasm but also included nuclear sites. To examine the suitability of the labeled lectin as a histochemical probe we biotinylated galectin-2 under activity-preserving conditions and introduced it to tissue profiling. Specific cytoplasmic staining proved the validity of the concept. Our results encourage systematic histopathologic studies by immuno- and lectin histochemistry, especially by adding galectin-2 as study object to galectin fingerprinting which has already yielded prognostic information on galectins-1, -3, -4 and -8 and hereby contributed to define functional overlap/divergence in this lectin family., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

Published
2005

37. Signaling axis involving Hedgehog, Notch, and Scl promotes the embryonic endothelial-to-hematopoietic transition

Author

Kim, Peter Geon, primary, Albacker, Colleen E., additional, Lu, Yi-fen, additional, Jang, Il-ho, additional, Lim, Yoowon, additional, Heffner, Garrett C., additional, Arora, Natasha, additional, Bowman, Teresa V., additional, Lin, Michelle I., additional, Lensch, M. William, additional, De Los Angeles, Alejandro, additional, Zon, Leonard I., additional, Loewer, Sabine, additional, and Daley, George Q., additional

Published
2012
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38. Erratum: Donor cell type can influence the epigenome and differentiation potential of human induced pluripotent stem cells

Author

Kim, Kitai, primary, Zhao, Rui, additional, Doi, Akiko, additional, Ng, Kitwa, additional, Unternaehrer, Juli, additional, Cahan, Patrick, additional, Hongguang, Huo, additional, Loh, Yuin-Han, additional, Aryee, Martin J, additional, Lensch, M William, additional, Li, Hu, additional, Collins, James J, additional, Feinberg, Andrew P, additional, and Daley, George Q, additional

Published
2012
Full Text
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39. Donor cell type can influence the epigenome and differentiation potential of human induced pluripotent stem cells

Author

Kim, Kitai, primary, Zhao, Rui, additional, Doi, Akiko, additional, Ng, Kitwa, additional, Unternaehrer, Juli, additional, Cahan, Patrick, additional, Hongguang, Huo, additional, Loh, Yuin-Han, additional, Aryee, Martin J, additional, Lensch, M William, additional, Li, Hu, additional, Collins, James J, additional, Feinberg, Andrew P, additional, and Daley, George Q, additional

Published
2011
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40. Research Spotlight

Author

Benvenisty, Nissim, primary, Dalton, Stephen, additional, Young, Lorraine, additional, Sussman, Mark, additional, and Lensch, M William, additional

Published
2011
Full Text
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