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2. The Role of Mesenchyme in Thymus Development

Author

Owen, J. J. T., McLoughlin, D. E., Suniara, R. K., Jenkinson, E. J., Compans, R. W., editor, Cooper, M., editor, Hogle, J. M., editor, Ito, Y., editor, Koprowski, H., editor, Melchers, F., editor, Oldstone, M., editor, Olsnes, S., editor, Potter, M., editor, Saedler, H., editor, Vogt, P. K., editor, Wagner, H., editor, and Melchers, Fritz, editor

Published
2000
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3. Potential Impact of the 2016 Consensus Definitions of Sepsis and Septic Shock on Future Sepsis Research

Author

Peake, Sandra L., Delaney, Anthony, Bailey, Michael, Bellomo, Rinaldo, Bennett, V., Board, J., McCracken, P., McGloughlin, S., Nanjayya, V., Teo, A., Hill, E., Jones, P., O’Brien, E., Sawtell, F., Schimanski, K., Wilson, D., Bellomo, R., Bolch, S., Eastwood, G., Kerr, F., Peak, L., Young, H., Edington, J., Fletcher, J., Smith, J., Ghelani, D., Nand, K., Sara, T., Cross, A., Flemming, D., Grummisch, M., Purdue, A., Fulton, E., Grove, K., Harney, A., Milburn, K., Millar, R., Mitchell, I., Rodgers, H., Scanlon, S., Coles, T., Connor, H., Dennett, J., Van Berkel, A., Barrington-Onslow, S., Henderson, S., Mehrtens, J., Dryburgh, J., Tankel, A., Braitberg, G., O’Bree, B., Shepherd, K., Vij, S., Allsop, S., Haji, D., Haji, K., Vuat, J., Bone, A., Elderkin, T., Orford, N., Ragg, M., Kelly, S., Stewart, D., Woodward, N., Harjola, V.-P., Okkonen, M., Pettilä, V., Sutinen, S., Wilkman, E., Fratzia, J., Halkhoree, J., Treloar, S., Ryan, K., Sandford, T., Walsham, J., Jenkins, C., Williamson, D., Burrows, J., Hawkins, D., Tang, C., Dimakis, A., Holdgate, A., Micallef, S., Parr, M., White, H., Morrison, L., Sosnowski, K., Ramadoss, R., Soar, N., Wood, J., Franks, M., Williams, A., Hogan, C., Song, R., Tilsley, A., Rainsford, D., Wells, R., Dowling, J., Galt, P., Lamac, T., Lightfoot, D., Walker, C., Braid, K., DeVillecourt, T., Tan, H. S., Seppelt, I., Chang, L. F., Cheung, W. S., Fok, S. K., Lam, P. K., Lam, S. M., So, H. M., Yan, W. W., Altea, A., Lancashire, B., Gomersall, C. D., Graham, C. A., Leung, P., Arora, S., Bass, F., Shehabi, Y., Isoardi, J., Isoardi, K., Powrie, D., Lawrence, S., Ankor, A., Chester, L., Davies, M., O’Connor, S., Poole, A., Soulsby, T., Sundararajan, K., Williams, J., Greenslade, J. H., MacIsaac, C., Gorman, K., Jordan, A., Moore, L., Ankers, S., Bird, S., Delaney, A., Fogg, T., Hickson, E., Jewell, T., Kyneur, K., O’Connor, A., Townsend, J., Yarad, E., Brown, S., Chamberlain, J., Cooper, J., Jenkinson, E., McDonald, E., Webb, S., Buhr, H., Coakley, J., Cowell, J., Hutch, D., Gattas, D., Keir, M., Rajbhandari, D., Rees, C., Baker, S., Roberts, B., Farone, E., Holmes, J., Santamaria, J., Winter, C., Finckh, A., Knowles, S., McCabe, J., Nair, P., Reynolds, C., Ahmed, B., Barton, D., Meaney, E., Nichol, A., Harris, R., Shields, L., Thomas, K., Karlsson, S., Kuitunen, A., Kukkurainen, A., Tenhunen, J., Varila, S., Ryan, N., Trethewy, C., Crosdale, J., Smith, J. C., Vellaichamy, M., Furyk, J., Gordon, G., Jones, L., Senthuran, S., Bates, S., Butler, J., French, C., Tippett, A., Kelly, J., Kwans, J., Murphy, M., O’Flynn, D., Kurenda, C., Otto, T., Peake, S., Raniga, V., Williams, P., Ho, H. F., Leung, A., and Wu, H.

Published
2017
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4. Worldwide Organization of Neurocritical Care: Results from the PRINCE Study Part 1

Author

Suarez, J. I., Martin, R. H., Bauza, C., Georgiadis, A., Venkatasubba Rao, C. P., Calvillo, E., Hemphill, J. C., Sung, G., Oddo, M., Taccone, Fabio Silvio, Leroux, P. D., Layon, A. J., Sarwal, A., Ali, A., Lele, A., Jarquin-Valdivia, A. A., Misiewska-Kaczur, A., Ahmad, A., Deeb, A. M., Jabbary, A. A., Fathy, A., Chan, A., Kern, CHRISTOPH ALEXANDER, Gritsan, A., Bshabshe, A. A., Malek, A., Schiefecker, A., Neto, A. R., ALHAJJ HASSAN, Ali, Zahrani, A. R. A., Sukumaran, A. V., Sarma, A. K., Aneman, A., Kramer, A., Naidech, A., Lacerda Gallardo, A. J., Miller, A., O'Connor, A., Kim, A., Afshinnik, A., Katila, A., Paulson, A., Parra, A., Rosengart, A., Almemari, A., Sanchez, B., Ray, B., Mccrum, B., Tegedor, B. V., Nathan, B., Tan, B., Emanuel, B., Pfaulser, B., Nazliel, B., Gil, B., Hightower, B., Francis, B., Roberts, B., Chaudhry, B., Romero, C., Graffagnino, C., VANDEN BERGHE, GREET CLARA, Hobohm, C., Dias, C., Bradford, C., Basignani, C., Chang, C., Junker, C., Lazaridis, C., Mcarthur, C., Williamson, C., Hebert, C., Ethan Kahn, D., Harvey, D., Laskowitz, D. T., Milzman, D., Chung, D., Greer, D., Seder, D., Miller, D. W., Barge, D., Roberts, D., Jordan, D., Bhonagiri, D., Nair, D., Aggarwal, D. G., Kutsogiannis, D. J., Laiwattana, D., Pinto, D. B., Bautista, D., Perez, D., Herrera, E. A., Singares, E. S., Manno, E., Wilensky, E. M., Giraldo, E. A., Jenkinson, E., Yarad, E., Zavala, E., Tesoro, E., Eskiogly, E., Bershad, E. M., Rosenthal, E., Coronel, E. B., Gordon, E., Salgado, E., Poch, E. J., Eriksson, E., Taccone, F. S., Al-Suwaidan, F., Sorond, F., Bilotta, F., Goldenberg, F. D., Rosciani, F., Bass, F., Bernard, F., Julian, F. B., Rasulo, F., Rincon, F., Santos, G., Anderson, G., Henderson, G., Meyfroidt, G., Wong, G. K. C., Aguilar, G., Rodriguez-Vega, G., Tamayo, G., Johnston, G., Kapinos, G., Abrego, G. C., Paul, G., Xu, G., Domeniconi, G., Dugan, G., Murthy, H. H. K., Peled, H., Zraiki, H., Alvarez, H., Rodgers, H., Vaitkevicius, H., Schumacher, H. C., Kobata, H., Al-Jehani, H., Lopez Delgado, H. J., Olmecah, H. M., Madrinan-Navia, H., Tran, H., Seppelt, I., Schirotzek, I., Medary, I. B., Maldonado, I. L., da Silva, I. R. F., Hemphill III, J. C., Javier Provencio, J., Mora, J. E., Abdullah, J. M., Langdon, J. R., Claassen, J., de Oliveira, J., Shilkin, J., Horn, J., Teitelbaum, J., Frank, J. I., Fletcher, J. J., Berkeley, J., Andersson, KIM JIMMY, Kirkwood, J., Welbourne, J., Song, J., Domingues, J. R. S., Paxton, J., Falla, J., Lokin, J., Dissin, J., Bonomo, J., Martinez, J. E., Mejia-Mantilla, J. H., Ramirez-Arce, J., Palo, J. E., Moretti, J. I., Gonzalez, J. R. Y., Levine, J. M., Medow, J., Pou, J. A. L., Ciro, J. D., Paucar, J. L. C., Wright, J. C., Bosel, J., Martinez, J., Mijangos-Mendez, J. C., Chalela, J., Granillo, J. F., Sohal, J., Hirsch, K. G., Donaldson, K., Cummings, K., Hubner, K. E., Wartenberg, K., Goyal, K., Sheth, K., Kunze, K., O'Phelan, K., Sheehan, K., Altaweel, L., Cross, L., Barrachina, L. G., Kuisle, L., Connolyy, L. S., Tack, L., Johnson, L., Shutter, L., Pelunkova, L., Ramos-Gomez, L. A., Camputaro, L. A., Kamran Athar, M., Madhusudan, M., Hashmi, M., Mokhtari, M., Jibaja, M., Muller, M. C. A., Costilla, M., Mirski, M., Ochoa, M. E., Pegoli, M., Dujardin, M. -F., Allasia, M., Teran, M. D., Gorman, Michael Murray, Chapman, M., Amatangelo, M., Nagayama, M., Dickinson, M., Koenig, M., Moreda, M., Berman, M., De Georgia, M., Kuiper, M., O'Leary, M., Rodricks, M., Schneck, M., Torbey, M., Defilippis, M., Meeker, M., Allen, David Michael, Llano, M., Villalobos, M., Treggiari, M., Tuppeny, M., Sharaby, M., Kottapally, M., Mcnett, M., Mcbride, M., Gomez, M., Varga, M., Kumar, M., Yazbeck, M. F., Smith, M., Stevenson Porter, N., Hammond, N., Karanjia, N., Sokhal, N., Singhal, N. S., Badjatia, N., Maldonado, N., Ko, N., Marinoff, N., Hernandez Aguilar, Orisel, Krauchi, O. R., Sanchez, O., Gomez, O., Rivera, O. S., Gilvaz, P. C., Raffa, P., Varelas, P., Promsin, P., Merlani, P., Shushma, P., Allan, P., Biston, P., Vespa, P., Amorim, P., de Azambuja Rodrigues, P. M., Hopkins, P., Hantson, P., Vanamoorthy, P., Gupta, P., Garvin, R., Badenes, R., Damani, R., Helbok, R., Dhar, R., Rawal, R., Carandang, R., Guisado, R., Luengo, R. -I. G., Sajjad, R., Davis, R., Rison, R. A., Hoesch, R., Murillo, R., Smith, R., Ball, R., Beer, R., Reshi, R. A., Landry, R., Puvanendiran, S., Ansari, S., Mukaddam, S., Garg, S., Mishra, S., Clark, S., Napolitano, Silvano, Pattnaik, S., Vosylius, S., John, S., Josephson, S. A., Glickman, S., Brehaut, S. S., Shiraz, S. A., Aguilera, S., Sternberg, S., Chou, S., Vallance, S., Lasocki, S., Schoenenberger, S., Bird, S., Finfer, S., Shieber, S., Vadi, S., Samavedam, S., Cordina, S., Feske, S., Glassner, S., Dixit, S., Dowling, S., Tena, S. A., Bowling, S., Francken, S., Muehlschlegel, S., Renard, S., Poli, S., Carter, T., Bleck, T. P., Trim, T., Breitenfeld, T., Van Bui, T., Shukla, U., Sinha, V., Rajajee, V., Aiyagari, V., Mccredie, V., Svigelj, V., Verma, V., Rao, V. A., David Freeman, W., Smith, W. S., Videtta, W., Habre, W., Hall, W., Coplin, W. M., Abdo, W. F., Wittebole, X., Titova, Y., PRINCE Study Investigators, Layon, A.J., Sarwal, A., Ali, A., Lele, A., Jarquin-Valdivia, A.A., Misiewska-Kaczur, A., Ahmad, A., Deeb, A.M., Jabbary, A.A., Fathy, A., Chan, A., Kern, A., Georgiadis, A., Gritsan, A., Bshabshe, A.A., Malek, A., Schiefecker, A., Neto, A.R., Hassan, A., Zahrani, ARA, Sukumaran, A.V., Sarma, A.K., Aneman, A., Kramer, A., Naidech, A., Lacerda Gallardo, A.J., Miller, A., O'Connor, A., Kim, A., Afshinnik, A., Katila, A., Paulson, A., Parra, A., Rosengart, A., Almemari, A., Sanchez, B., Ray, B., McCrum, B., Tegedor, B.V., Nathan, B., Tan, B., Emanuel, B., Pfaulser, B., Nazliel, B., Gil, B., Hightower, B., Francis, B., Roberts, B., Chaudhry, B., Romero, C., Graffagnino, C., Berghe, C., Hobohm, C., Dias, C., Bradford, C., Basignani, C., Chang, C., Venkatasubba Rao, C.P., Junker, C., Lazaridis, C., McArthur, C., Williamson, C., Hebert, C., Ethan Kahn, D., Harvey, D., Laskowitz, D.T., Milzman, D., Chung, D., Greer, D., Seder, D., Miller, D.W., Barge, D., Roberts, D., Jordan, D., Bhonagiri, D., Nair, D., Aggarwal, D.G., Kutsogiannis, D.J., Laiwattana, D., Pinto, D.B., Bautista, D., Perez, D., Herrera, E.A., Singares, E.S., Manno, E., Wilensky, E.M., Giraldo, E.A., Jenkinson, E., Yarad, E., Zavala, E., Tesoro, E., Eskiogly, E., Bershad, E.M., Rosenthal, E., Coronel, E.B., Gordon, E., Salgado, E., Poch, E.J., Calvillo, E., Eriksson, E., Taccone, F.S., Al-Suwaidan, F., Sorond, F., Bilotta, F., Goldenberg, F.D., Rosciani, F., Bass, F., Bernard, F., Julian, F.B., Rasulo, F., Rincon, F., Santos, G., Anderson, G., Henderson, G., Meyfroidt, G., Sung, G., Wong, GKC, Aguilar, G., Rodriguez-Vega, G., Tamayo, G., Johnston, G., Kapinos, G., Abrego, G.C., Paul, G., Xu, G., Domeniconi, G., Dugan, G., Murthy, HHK, Peled, H., Zraiki, H., Alvarez, H., Rodgers, H., Vaitkevicius, H., Schumacher, H.C., Kobata, H., Al-Jehani, H., Lopez Delgado, H.J., Olmecah, H.M., Madrinan-Navia, H., Tran, H., Seppelt, I., Schirotzek, I., Medary, I.B., Maldonado, I.L., da Silva, IRF, Hemphill Iii, J.C., Javier Provencio, J., Mora, J.E., Abdullah, J.M., Langdon, J.R., Claassen, J., de Oliveira, J., Shilkin, J., Horn, J., Teitelbaum, J., Frank, J.I., Fletcher, J.J., Berkeley, J., Kim, J., Kirkwood, J., Welbourne, J., Song, J., Domingues, JRS, Paxton, J., Falla, J., Lokin, J., Dissin, J., Bonomo, J., Martinez, J.E., Mejia-Mantilla, J.H., Ramirez-Arce, J., Palo, J.E., Moretti, J.I., Suarez, J.I., Gonzalez, JRY, Levine, J.M., Medow, J., Pou, JAL, Ciro, J.D., Paucar, JLC, Wright, J.C., Bosel, J., Martinez, J., Mijangos-Mendez, J.C., Chalela, J., Granillo, J.F., Sohal, J., Hirsch, K.G., Donaldson, K., Cummings, K., Hubner, K.E., Wartenberg, K., Goyal, K., Sheth, K., Kunze, K., O'Phelan, K., Sheehan, K., Altaweel, L., Cross, L., Barrachina, L.G., Kuisle, L., Connolyy, L.S., Tack, L., Johnson, L., Shutter, L., Pelunkova, L., Ramos-Gomez, L.A., Camputaro, L.A., Kamran Athar, M., Madhusudan, M., Hashmi, M., Mokhtari, M., Jibaja, M., Muller, MCA, Costilla, M., Mirski, M., Ochoa, M.E., Pegoli, M., Dujardin, M.F., Allasia, M., Teran, M.D., Gorman, M., Chapman, M., Amatangelo, M., Nagayama, M., Dickinson, M., Koenig, M., Moreda, M., Berman, M., De Georgia, M., Kuiper, M., O'Leary, M., Rodricks, M., Schneck, M., Torbey, M., DeFilippis, M., Meeker, M., Allen, M., Llano, M., Villalobos, M., Treggiari, M., Tuppeny, M., Sharaby, M., Kottapally, M., McNett, M., McBride, M., Gomez, M., Varga, M., Kumar, M., Yazbeck, M.F., Smith, M., Stevenson Porter, N., Hammond, N., Karanjia, N., Sokhal, N., Singhal, N.S., Badjatia, N., Maldonado, N., Ko, N., Marinoff, N., Hernandez, O., Krauchi, O.R., Sanchez, O., Gomez, O., Rivera, O.S., Gilvaz, P.C., Raffa, P., Varelas, P., Promsin, P., Merlani, P., Shushma, P., Allan, P., Biston, P., Vespa, P., Amorim, P., de Azambuja Rodrigues, P.M., Hopkins, P., Hantson, P., Vanamoorthy, P., Gupta, P., Garvin, R., Badenes, R., Damani, R., Helbok, R., Dhar, R., Rawal, R., Carandang, R., Guisado, R., Luengo, R.G., Sajjad, R., Davis, R., Rison, R.A., Hoesch, R., Murillo, R., Smith, R., Ball, R., Beer, R., Reshi, R.A., Landry, R., Puvanendiran, S., Ansari, S., Mukaddam, S., Garg, S., Mishra, S., Clark, S., Napolitano, S., Pattnaik, S., Vosylius, S., John, S., Josephson, S.A., Glickman, S., Brehaut, S.S., Shiraz, S.A., Aguilera, S., Sternberg, S., Chou, S., Vallance, S., Lasocki, S., Schoenenberger, S., Bird, S., Finfer, S., Shieber, S., Vadi, S., Samavedam, S., Cordina, S., Feske, S., Glassner, S., Dixit, S., Dowling, S., Tena, S.A., Bowling, S., Francken, S., Muehlschlegel, S., Renard, S., Poli, S., Carter, T., Bleck, T.P., Trim, T., Breitenfeld, T., Van Bui, T., Shukla, U., Sinha, V., Rajajee, V., Aiyagari, V., McCredie, V., Svigelj, V., Verma, V., Rao, V.A., David Freeman, W., Smith, W.S., Videtta, W., Habre, W., Hall, W., Coplin, W.M., Abdo, W.F., Wittebole, X., Titova, Y., Intensive Care Medicine, ANS - Neuroinfection & -inflammation, Other Research, ACS - Pulmonary hypertension & thrombosis, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, and UCL - (SLuc) Service de soins intensifs

Subjects
Internationality, Scope of practice, Latin Americans, medicine.medical_treatment, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Pharmacists, Critical Care and Intensive Care Medicine, law.invention, 0302 clinical medicine, Clinical Protocols, Central Nervous System Diseases, law, Observational study, Epidemiology, Neurocritical care, Case report form, Academic Medical Centers, Intensive care unit, Telemedicine, Europe, Intensive Care Units, Prospective, Transportation of Patients, Neurology, Practice Guidelines as Topic, Critical care, Outcomes, Original Work, Respiratory Therapy, medicine.medical_specialty, Asia, Tomography Scanners, X-Ray Computed, Critical Care, Health Personnel, Oceania, Respiratory therapist, Neurosurgery, Pharmacist, Personnel Management, Resource Allocation, Middle East, 03 medical and health sciences, Physicians, medicine, Humans, Fellowships and Scholarships, business.industry, Internship and Residency, Neurointensive care, 030208 emergency & critical care medicine, Latin America, Family medicine, North America, Neurology (clinical), business, Delivery of Health Care, 030217 neurology & neurosurgery
Abstract

Introduction Neurocritical care focuses on the care of critically ill patients with an acute neurologic disorder and has grown significantly in the past few years. However, there is a lack of data that describe the scope of practice of neurointensivists and epidemiological data on the types of patients and treatments used in neurocritical care units worldwide. To address these issues, we designed a multicenter, international, point-prevalence, cross-sectional, prospective, observational, non-interventional study in the setting of neurocritical care (PRINCE Study). Methods In this manuscript, we analyzed data from the initial phase of the study that included registration, hospital, and intensive care unit (ICU) organizations. We present here descriptive statistics to summarize data from the registration case report form. We performed the Kruskal–Wallis test followed by the Dunn procedure to test for differences in practices among world regions. Results We analyzed information submitted by 257 participating sites from 47 countries. The majority of those sites, 119 (46.3%), were in North America, 44 (17.2%) in Europe, 34 (13.3%) in Asia, 9 (3.5%) in the Middle East, 34 (13.3%) in Latin America, and 14 (5.5%) in Oceania. Most ICUs are from academic institutions (73.4%) located in large urban centers (44% > 1 million inhabitants). We found significant differences in hospital and ICU organization, resource allocation, and use of patient management protocols. The highest nursing/patient ratio was in Oceania (100% 1:1). Dedicated Advanced Practiced Providers are mostly present in North America (73.7%) and are uncommon in Oceania (7.7%) and the Middle East (0%). The presence of dedicated respiratory therapist is common in North America (85%), Middle East (85%), and Latin America (84%) but less common in Europe (26%) and Oceania (7.7%). The presence of dedicated pharmacist is highest in North America (89%) and Oceania (85%) and least common in Latin America (38%). The majority of respondents reported having a dedicated neuro-ICU (67% overall; highest in North America: 82%; and lowest in Oceania: 14%). Conclusion The PRINCE Study results suggest that there is significant variability in the delivery of neurocritical care. The study also shows it is feasible to undertake international collaborations to gather global data about the practice of neurocritical care. Electronic supplementary material The online version of this article (10.1007/s12028-019-00750-3) contains supplementary material, which is available to authorized users.

Published
2020

6. Global Survey of Outcomes of Neurocritical Care Patients: Analysis of the PRINCE Study Part 2

Author

Rao C, Suarez J, Martin R, Bauza C, Georgiadis A, Calvillo E, Hemphill J, Sung G, Oddo M, Taccone F, LeRoux P, Domeniconi G, Camputaro L, Villalobos M, Allasia M, Goldenberg F, Teran M, Rosciani F, Alvarez H, Costilla M, Videtta W, Perez D, Raffa P, Seppelt I, Rodgers H, Paxton J, Bhonagiri D, Aneman A, Jenkinson E, Bradford C, Finfer S, Yarad E, Bass F, Hammond N, O'Connor A, Bird S, Smith R, Barge D, Shilkin J, Woods W, Roberts B, O'Leary M, Vallance S, Helbok R, Beer R, Pfaulser B, Schiefecker A, Almemari A, Mukaddam S, Wittebole X, Berghe C, Dujardin M, Renard S, Hantson P, Biston P, Meyfroidt G, da Silva I, de Oliveira J, Neto A, Domingues J, Rodrigues P, Teitelbaum J, Chapman M, McCredie V, Marinoff N, Perez A, Kutsogiannis D, Bernard F, Kramer A, Moretti J, Aguilera S, Poch E, Romero C, Wong G, Song J, Xu G, Mejia-Mantilla J, Madrinan-Navia H, Martinez J, Ochoa M, Bautista D, Varga M, Gomez M, Ciro J, Gil B, Murillo R, Hernandez O, Ramirez-Arce J, Breitenfeld T, Gallardo A, Delgado H, Gonzalez J, Hache-Marliere M, Pinto D, Llano M, Salgado E, Jibaja M, Wright J, Harvey D, Verma V, Hopkins P, Chan A, Welbourne J, Dowling S, Katila A, Lasocki S, Wartenberg K, Hobohm C, Poli S, Schirotzek I, Bosel J, Schoenenberger S, Francken S, Shieber S, Kern A, Falla J, Herrera E, Gilvaz P, Goyal K, Sokhal N, Sohal J, Aggarwal D, Ray B, Pattnaik S, Garg S, Dixit S, Rawal R, Samavedam S, Madhusudan M, Paul G, Mishra S, Shushma P, Shukla U, Sinha V, Vanamoorthy P, Vadi S, Mokhtari M, Rasulo F, Pegoli M, Bilotta F, Nagayama M, Kobata H, Vosylius S, Abdullah J, Granillo J, Mijangos-Mendez J, Horn J, Muller M, Kuiper M, Abdo W, McArthur C, Newby L, Hashmi M, Shiraz S, Abrego G, Coronel E, Rivera O, Paucar J, Gomez O, Palo J, Lokin J, Misiewska-Kaczur A, Dias C, Amorim P, Andre S, Rodriguez-Vega G, Gritsan A, Titova Y, Al Jabbary A, Al Zahrani A, Pelunkova L, Zraiki H, Deeb A, Al Bshabshe A, Al-Jehani H, Al-Suwaidan F, Svigelj V, Ramos-Gomez L, Aguilar G, Badenes R, Pou J, Zavala E, Julian F, Barrachina L, Tegedor B, Tena S, Krauchi O, Tamayo G, Sanchez B, Gonzalezluengo R, Puvanendiran S, Merlani P, Laiwattana D, Promsin P, Nazliel B, Eriksson E, Chalela J, Miller D, Guisado R, Gordon E, Murthy H, Paulson A, Rajajee V, Sheehan K, Williamson C, Ball R, Allan P, Berkeley J, Muehlschlegel S, Carandang R, Hall W, Sarwal A, Damani R, Maldonado N, Tan B, Gupta P, Lazaridis C, Bershad E, Ansari S, Singares E, Manno E, Provencio J, Chaudhry B, McBride M, Dhar R, Roberts D, Allen M, Schumacher H, Habre W, Sheth K, Greer D, Kunze K, Varelas P, Tack L, Porter N, Junker C, Rodricks M, Tuppeny M, Basignani C, Napolitano S, Anderson G, Donaldson K, Davis R, Sternberg S, Giraldo E, Tran H, Coplin W, Badjatia N, Fathy A, Reshi R, Bonomo J, Seder D, Connolyy L, McCrum B, Carter T, Treggiari M, Dickinson M, Rison R, Mirski M, John S, Bleck T, Malek A, Trim T, Smith M, Athar M, Rincon F, Altaweel L, Vespa P, Emanuel B, Eskiogly E, McNett M, Sukumaran A, Shutter L, Milzman D, Glassner S, OPhelan K, Rosenthal E, Kottapally M, Smith W, Ko N, Josephson S, Kim A, Singhal N, Ahmad A, Meeker M, Hirsch K, Nair D, Chou S, Santos G, Clark S, Feske S, Henderson G, Sorond F, Vaitkevicius H, Chung D, Kim J, Amatangelo M, Kapinos G, Torbey M, Kahn D, Chang C, Koenig M, Gorman M, Langdon J, Dissin J, Cross L, Peled H, Claassen J, Ali A, Layon A, Miller A, Wilensky E, Kumar M, Levine J, Maldonado I, Schneck M, Lele A, Sarma A, Yazbeck M, Johnston G, Jarquin-Valdivia A, Johnson L, Kuisle L, Sajjad R, Glickman S, Garvin R, Parra A, DeFilippis M, Fletcher J, Freeman W, Rao V, Olmecah H, Dugan G, Medary I, Hoesch R, Brehaut S, Afshinnik A, Moreda M, Graffagnino C, Laskowitz D, Naidech A, Francis B, Berman M, Tesoro E, Medow J, Jordan D, Aiyagari V, Rosengart A, De Georgia M, Bowling S, Sharaby M, Nathan B, Landry R, Hebert C, Hubner K, Karanjia N, Hightower B, Cummings K, Kirkwood J, Frank J, Hassan A, Sanchez O, Cordina S, Mora J, Bui T, PRINCE Study Investigators, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service de soins intensifs, and Meyfroidt, Geert

Subjects
medicine.medical_specialty, IMPACT, NEUROSCIENCES, Clinical Neurology, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], TRAUMATIC BRAIN-INJURY, UNITED-STATES, Outcomes, INTENSIVE-CARE, Critical Care and Intensive Care Medicine, Logistic regression, VALIDATION, 03 medical and health sciences, 0302 clinical medicine, Critical Care Medicine, General & Internal Medicine, Observational study, Intensive care, Severity of illness, Epidemiology, Neurocritical care, Medicine, Case report form, Science & Technology, business.industry, LENGTH-OF-STAY, Glasgow Coma Scale, Neurointensive care, 030208 emergency & critical care medicine, Critical care, Prospective, Emergency medicine, PATTERNS, Neurosciences & Neurology, Neurology (clinical), business, Life Sciences & Biomedicine, CRITICALLY-ILL PATIENTS, GLASGOW COMA SCALE, 030217 neurology & neurosurgery
Abstract

Contains fulltext : 218566pub.pdf (Publisher’s version ) (Closed access) Contains fulltext : 218566pos.pdf (Author’s version postprint ) (Open Access) BACKGROUND: Neurocritical care is devoted to the care of critically ill patients with acute neurological or neurosurgical emergencies. There is limited information regarding epidemiological data, disease characteristics, variability of clinical care, and in-hospital mortality of neurocritically ill patients worldwide. We addressed these issues in the Point PRevalence In Neurocritical CarE (PRINCE) study, a prospective, cross-sectional, observational study. METHODS: We recruited patients from various intensive care units (ICUs) admitted on a pre-specified date, and the investigators recorded specific clinical care activities they performed on the subjects during their first 7 days of admission or discharge (whichever came first) from their ICUs and at hospital discharge. In this manuscript, we analyzed the final data set of the study that included patient admission characteristics, disease type and severity, ICU resources, ICU and hospital length of stay, and in-hospital mortality. We present descriptive statistics to summarize data from the case report form. We tested differences between geographically grouped data using parametric and nonparametric testing as appropriate. We used a multivariable logistic regression model to evaluate factors associated with in-hospital mortality. RESULTS: We analyzed data from 1545 patients admitted to 147 participating sites from 31 countries of which most were from North America (69%, N = 1063). Globally, there was variability in patient characteristics, admission diagnosis, ICU treatment team and resource allocation, and in-hospital mortality. Seventy-three percent of the participating centers were academic, and the most common admitting diagnosis was subarachnoid hemorrhage (13%). The majority of patients were male (59%), a half of whom had at least two comorbidities, and median Glasgow Coma Scale (GCS) of 13. Factors associated with in-hospital mortality included age (OR 1.03; 95% CI, 1.02 to 1.04); lower GCS (OR 1.20; 95% CI, 1.14 to 1.16 for every point reduction in GCS); pupillary reactivity (OR 1.8; 95% CI, 1.09 to 3.23 for bilateral unreactive pupils); admission source (emergency room versus direct admission [OR 2.2; 95% CI, 1.3 to 3.75]; admission from a general ward versus direct admission [OR 5.85; 95% CI, 2.75 to 12.45; and admission from another ICU versus direct admission [OR 3.34; 95% CI, 1.27 to 8.8]); and the absence of a dedicated neurocritical care unit (NCCU) (OR 1.7; 95% CI, 1.04 to 2.47). CONCLUSION: PRINCE is the first study to evaluate care patterns of neurocritical patients worldwide. The data suggest that there is a wide variability in clinical care resources and patient characteristics. Neurological severity of illness and the absence of a dedicated NCCU are independent predictors of in-patient mortality.

Published
2019

13. Gender differences in mortality and quality of life after septic shock: A post-hoc analysis of the ARISE study

Author

Luethi, N, Bailey, M, Higgins, A, Howe, B, Peake, S, Delaney, A, Bellomo, R, Bennett, V, Board, J, McCracken, P, McGloughlin, S, Nanjayya, V, Teo, A, Hill, E, O'Brien, PJE, Sawtell, F, Schimanski, K, Wilson, D, Bolch, S, Eastwood, G, Kerr, F, Peak, L, Young, H, Edington, J, Fletcher, J, Smith, J, Ghelani, D, Nand, K, Sara, T, Cross, A, Flemming, D, Grummisch, M, Purdue, A, Fulton, E, Grove, K, Harney, A, Milburn, K, Millar, R, Mitchell, I, Rodgers, H, Scanlon, S, Coles, T, Connor, H, Dennett, J, Van Berkel, A, Barrington-Onslow, S, Henderson, S, Mehrtens, J, Dryburgh, J, Tankel, A, Braitberg, G, O'Bree, B, Shepherd, K, Vij, S, Allsop, S, Haji, D, Haji, K, Vuat, J, Bone, A, Elderkin, T, Orford, N, Ragg, M, Kelly, S, Stewart, D, Woodward, N, Harjola, V-P, Pettila, MO, Sutinen, S, Wilkman, E, Fratzia, J, Halkhoree, J, Treloar, S, Ryan, K, Sandford, T, Walsham, J, Jenkins, C, Williamson, D, Burrows, J, Hawkins, D, Tang, C, Dimakis, A, Holdgate, A, Micallef, S, Parr, M, White, H, Morrison, L, Sosnowski, K, Ramadoss, R, Soar, N, Wood, J, Franks, M, Williams, A, Hogan, C, Song, R, Tilsley, A, Rainsford, D, Wells, R, Dowling, J, Galt, P, Lamac, T, Lightfoot, D, Walker, C, Braid, K, DeVillecourt, T, Tan, HS, Seppelt, I, Chang, LF, Cheung, WS, Fok, SK, Lam, PK, Lam, SM, So, HM, Yan, W, Altea, A, Lancashire, B, Gomersall, CD, Graham, CA, Leung, P, Arora, S, Bass, F, Shehabi, Y, Isoardi, J, Isoardi, K, Powrie, D, Lawrence, S, Ankor, A, Chester, L, Davies, M, O'Connor, S, Poole, A, Soulsby, T, Sundararajan, K, Williams, J, Greenslade, JH, MacIsaac, C, Gorman, K, Jordan, A, Moore, L, Ankers, S, Bird, S, Fogg, T, Hickson, E, Jewell, T, Kyneur, K, O'Connor, A, Townsend, J, Yarad, E, Brown, S, Chamberlain, J, Cooper, J, Jenkinson, E, McDonald, E, Webb, S, Buhr, H, Coakley, J, Cowell, J, Hutch, D, Gattas, D, Keir, M, Rajbhandari, D, Rees, C, Baker, S, Roberts, B, Farone, E, Holmes, J, Santamaria, J, Winter, C, Finckh, A, Knowles, S, McCabe, J, Nair, P, Reynolds, C, Ahmed, B, Barton, D, Meaney, E, Nichol, A, Harris, R, Shields, L, Thomas, K, Karlsson, S, Kuitunen, A, Kukkurainen, A, Tenhunen, J, Varila, S, Ryan, N, Trethewy, C, Crosdale, J, Smith, JC, Vellaichamy, M, Furyk, J, Gordon, G, Jones, L, Senthuran, S, Bates, S, Butler, J, French, C, Tippett, A, Kelly, J, Kwans, J, Murphy, M, O'Flynn, D, Kurenda, C, Otto, T, Raniga, V, Williams, P, Ho, HF, Leung, A, Wu, H, Luethi, N, Bailey, M, Higgins, A, Howe, B, Peake, S, Delaney, A, Bellomo, R, Bennett, V, Board, J, McCracken, P, McGloughlin, S, Nanjayya, V, Teo, A, Hill, E, O'Brien, PJE, Sawtell, F, Schimanski, K, Wilson, D, Bolch, S, Eastwood, G, Kerr, F, Peak, L, Young, H, Edington, J, Fletcher, J, Smith, J, Ghelani, D, Nand, K, Sara, T, Cross, A, Flemming, D, Grummisch, M, Purdue, A, Fulton, E, Grove, K, Harney, A, Milburn, K, Millar, R, Mitchell, I, Rodgers, H, Scanlon, S, Coles, T, Connor, H, Dennett, J, Van Berkel, A, Barrington-Onslow, S, Henderson, S, Mehrtens, J, Dryburgh, J, Tankel, A, Braitberg, G, O'Bree, B, Shepherd, K, Vij, S, Allsop, S, Haji, D, Haji, K, Vuat, J, Bone, A, Elderkin, T, Orford, N, Ragg, M, Kelly, S, Stewart, D, Woodward, N, Harjola, V-P, Pettila, MO, Sutinen, S, Wilkman, E, Fratzia, J, Halkhoree, J, Treloar, S, Ryan, K, Sandford, T, Walsham, J, Jenkins, C, Williamson, D, Burrows, J, Hawkins, D, Tang, C, Dimakis, A, Holdgate, A, Micallef, S, Parr, M, White, H, Morrison, L, Sosnowski, K, Ramadoss, R, Soar, N, Wood, J, Franks, M, Williams, A, Hogan, C, Song, R, Tilsley, A, Rainsford, D, Wells, R, Dowling, J, Galt, P, Lamac, T, Lightfoot, D, Walker, C, Braid, K, DeVillecourt, T, Tan, HS, Seppelt, I, Chang, LF, Cheung, WS, Fok, SK, Lam, PK, Lam, SM, So, HM, Yan, W, Altea, A, Lancashire, B, Gomersall, CD, Graham, CA, Leung, P, Arora, S, Bass, F, Shehabi, Y, Isoardi, J, Isoardi, K, Powrie, D, Lawrence, S, Ankor, A, Chester, L, Davies, M, O'Connor, S, Poole, A, Soulsby, T, Sundararajan, K, Williams, J, Greenslade, JH, MacIsaac, C, Gorman, K, Jordan, A, Moore, L, Ankers, S, Bird, S, Fogg, T, Hickson, E, Jewell, T, Kyneur, K, O'Connor, A, Townsend, J, Yarad, E, Brown, S, Chamberlain, J, Cooper, J, Jenkinson, E, McDonald, E, Webb, S, Buhr, H, Coakley, J, Cowell, J, Hutch, D, Gattas, D, Keir, M, Rajbhandari, D, Rees, C, Baker, S, Roberts, B, Farone, E, Holmes, J, Santamaria, J, Winter, C, Finckh, A, Knowles, S, McCabe, J, Nair, P, Reynolds, C, Ahmed, B, Barton, D, Meaney, E, Nichol, A, Harris, R, Shields, L, Thomas, K, Karlsson, S, Kuitunen, A, Kukkurainen, A, Tenhunen, J, Varila, S, Ryan, N, Trethewy, C, Crosdale, J, Smith, JC, Vellaichamy, M, Furyk, J, Gordon, G, Jones, L, Senthuran, S, Bates, S, Butler, J, French, C, Tippett, A, Kelly, J, Kwans, J, Murphy, M, O'Flynn, D, Kurenda, C, Otto, T, Raniga, V, Williams, P, Ho, HF, Leung, A, and Wu, H

Abstract

PURPOSE: To assess the impact of gender and pre-menopausal state on short- and long-term outcomes in patients with septic shock. MATERIAL AND METHODS: Cohort study of the Australasian Resuscitation in Sepsis Evaluation (ARISE) trial, an international randomized controlled trial comparing early goal-directed therapy (EGDT) to usual care in patients with early septic shock, conducted between October 2008 and April 2014. The primary exposure in this analysis was legal gender and the secondary exposure was pre-menopausal state defined by chronological age (≤ 50 years). RESULTS: 641 (40.3%) of all 1591 ARISE trial participants in the intention-to-treat population were females and overall, 337 (21.2%) (146 females) patients were 50 years of age or younger. After risk-adjustment, we could not identify any survival benefit for female patients at day 90 in the younger (≤50 years) (adjusted Odds Ratio (aOR): 0.91 (0.46-1.89), p = .85) nor in the older (>50 years) age-group (aOR: 1.10 (0.81-1.49), p = .56). Similarly, there was no gender-difference in ICU, hospital, 1-year mortality nor quality of life measures. CONCLUSIONS: This post-hoc analysis of a large multi-center trial in early septic shock has shown no short- or long-term survival effect for women overall as well as in the pre-menopausal age-group.

Published
2020

31. Hepcidin predicts response to IV iron therapy in patients admitted to the intensive care unit: A nested cohort study

Author

Litton, E., Baker, S., Erber, W., Farmer, Shannon, Ferrier, J., French, C., Gummer, J., Hawkins, D., Higgins, A., Hofmann, A., De Keulenaer, B., McMorrow, J., Olynyk, John, Richards, T., Towler, S., Trengove, R., Webb, S., Chapman, A., Jenkinson, E., Palermo, A., Roberts, B., Litton, E., Baker, S., Erber, W., Farmer, Shannon, Ferrier, J., French, C., Gummer, J., Hawkins, D., Higgins, A., Hofmann, A., De Keulenaer, B., McMorrow, J., Olynyk, John, Richards, T., Towler, S., Trengove, R., Webb, S., Chapman, A., Jenkinson, E., Palermo, A., and Roberts, B.

Abstract

© 2018 The Author(s). Background: Both anaemia and red blood cell (RBC) transfusion are common and associated with adverse outcomes in patients admitted to the intensive care unit (ICU). The aim of this study was to determine whether serum hepcidin concentration, measured early after ICU admission in patients with anaemia, could identify a group in whom intravenous (IV) iron therapy decreased the subsequent RBC transfusion requirement. Methods: We conducted a prospective observational study nested within a multicenter randomized controlled trial (RCT) of IV iron versus placebo. The study was conducted in the ICUs of four tertiary hospitals in Perth, Western Australia. Critically ill patients with haemoglobin (Hb) of <100g/L and within 48h of admission to the ICU were eligible for participation after enrolment in the IRONMAN RCT. The response to IV iron therapy compared with placebo was assessed according to tertile of hepcidin concentration. Results: Hepcidin concentration was measured within 48h of ICU admission in 133 patients. For patients in the lower two tertiles of hepcidin concentration (<53.0µg), IV iron therapy compared with placebo was associated with a significant decrease in RBC transfusion requirement [risk ratio 0.48 (95% CI 0.26-0.85), p=0.013]. Conclusions: In critically ill patients with anaemia admitted to an ICU, baseline hepcidin concentration predicts RBC transfusion requirement and is able to identify a group of patients in whom IV iron compared with placebo is associated with a significant decrease in RBC transfusion requirement.

Published
2018

35. Thymic Stem Cells: Their Interaction with the Thymic Stroma and Tolerance Induction

Author

Owen, J. J. T., Jenkinson, E. J., Kingston, R., Clarke, A., editor, Compans, R. W., editor, Cooper, M., editor, Eisen, H., editor, Goebel, W., editor, Koprowski, H., editor, Melchers, F., editor, Oldstone, M., editor, Rott, R., editor, Vogt, P. K., editor, Wagner, H., editor, Wilson, I., editor, Fleischer, Bernhard, editor, Reimann, Jörg, editor, and Wagner, Hermann, editor

Published
1986
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36. The Role of the Thymus in the Development of T-Cells

Author

Owen, J. J. T., Jenkinson, E. J., Kingston, R., Williams, G. T., Smith, C. A., Melchers, Fritz, editor, Albert, E. D., editor, von Boehmer, H., editor, Dierich, M. P., editor, Du Pasquier, L., editor, Eichmann, K., editor, Gemsa, D., editor, Götze, O., editor, Kalden, J. R., editor, Kaufmann, S. H. E., editor, Kirchner, H., editor, Resch, K., editor, Riethmüller, G., editor, Schimpl, A., editor, Sorg, C., editor, Steinmetz, M., editor, Wagner, H., editor, and Zachau, H. G., editor

Published
1989
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38. Comprehensive molecular screening strategy of OCLN in band‐like calcification with simplified gyration and polymicrogyria.

Author

Jenkinson, E. M., Livingston, J. H., O'Driscoll, M. C., Desguerre, I., Nabbout, R., Boddaert, N., Soares, G., Gonçalves da Rocha, M., D'Arrigo, S., Rice, G. I., and Crow, Y. J.

Subjects
*OCCLUDINS, *MOLECULAR diagnosis, *CALCIFICATION, *TIGHT junctions, *EPITHELIAL cells
Abstract

Occludin (OCLN) is an important component of the tight junction complex, providing apical intercellular connections between adjacent cells in endothelial and epithelial tissue. In 2010 O'Driscoll et al reported mutations in OCLN to cause band‐like calcification with simplified gyration and polymicrogyria (BLC‐PMG). BLC‐PMG is a rare autosomal recessive syndrome, characterized by early onset seizures, progressive microcephaly, severe developmental delay and deep cortical gray matter and basal ganglia calcification with symmetrical, predominantly fronto‐parietal, polymicrogyria. Here we report 4 additional cases of BLC‐PMG with novel OCLN mutations, and provide a summary of the published mutational spectrum. More generally, we describe a comprehensive molecular screening strategy taking into account the technical challenges associated with the genetic architecture of OCLN, which include the presence of a pseudo‐gene and copy number variants. [ABSTRACT FROM AUTHOR]

Published
2018
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39. Positive selection of thymocytes involves sustained interactions with the thymic microenvironment

Author

Wilkinson, R. W., graham anderson, Owen, J. J. T., and Jenkinson, E. J.

Subjects
Immunology, Immunology and Allergy
Abstract

CD4+8+ cortical thymocytes are critically dependent upon interaction with the thymic epithelium to undergo positive selection and maturation into single-positive CD4+ or CD8+ cells. Here we investigate further the nature of this interaction and provide evidence that positive selection requires sustained, rather than "single hit," interaction with thymic stromal cells. We also show that calcineurin-mediated signaling in thymocytes is required for the initial stages of positive selection, but is not essential throughout the period of thymocyte dependence on stromal cell contact during positive selection. In addition, we show that double-positive thymocytes that have initiated positive selection (CD69+4+8+) and newly generated single-positive (CD69+4+) cells differ markedly in response to the same stimulus through the TCR. The former undergo deletion, whereas the latter proliferate, indicating that a critical change in response to TCR ligation occurs within the narrow developmental window between these two stages.

Published
1995

40. Differential expression of Mtv loci in MHC class II-positive thymic stromal cells

Author

Moore, N. C., graham anderson, Mcloughlin, D. E. J., Owen, J. J. T., and Jenkinson, E. J.

Subjects
Immunology, Immunology and Allergy
Abstract

Despite the important role played by endogenous superantigen in shaping the T cell repertoire, little is known concerning the expression of the different Mtv loci in cells of the thymic microenvironment involved in repertoire selection. Here we have examined the expression of a panel of Mtv Ags by different MHC class II+ stromal cel types using reverse transcriptase-PCR and monitored the effects of these stromal cells on the development of cells expressing Mtv-reactive TCR V beta elements in closed thymic organ culture systems. Although Mtv-6 and Mtv-8/9 mRNAs are expressed in normal thymus lobe organ cultures, no Mtv expression was detected in MHC class II+ thymic epithelial cells. In contrast a striking pattern of differential expression was observed in dendritic cells of thymic origin that were devoid of Mtv-8/9 but expressed readily detectable levels of Mtv-6. This pattern of Mtv gene expression correlated well with TCR V beta repertoire development. TCRV beta 3+ T cells, normally deleted in response to Mtv-6, were virtually absent from the single positive thymocyte compartment in thymic organ cultures where dendritic cells are present but were present in reaggregate cultures where the only MHC class II-positive cells were thymic epithelial cells. On the other hand, V beta 11+ T-cells were not deleted in organ cultures, possibly reflecting the absence of Mtv-8/9 expression in dendritic cells. Our studies suggest that the influence Mtvs have on shaping the T cell repertoire not only depends on their expression within a particular strain but also on their tissue specific expression in relation to MHC class II, which is necessary for their presentation.

Published
1994

46. Specialized ability of thymic epithelial cells to mediate positive selection does not require expression of the steroidogenic enzyme p450scc

Author

Jenkinson, E. J., Parnell, S., Shuttleworth, J., Owen, J. J. T., and graham anderson

Subjects
Antigens, Differentiation, T-Lymphocyte, Mice, Inbred BALB C, Immunology, Histocompatibility Antigens Class II, Receptors, Antigen, T-Cell, Cell Differentiation, Epithelial Cells, Thymus Gland, Embryo, Mammalian, Mice, Organ Culture Techniques, Antigens, CD, Immunology and Allergy, Animals, Lectins, C-Type, Cholesterol Side-Chain Cleavage Enzyme, RNA, Messenger, Stromal Cells, Glucocorticoids, Cell Aggregation, Signal Transduction
Abstract

Thymic epithelial cells are uniquely efficient in mediating positive selection, suggesting that in addition to providing peptide/MHC complexes for TCR ligation, they may also provide additional support for this process. Recent studies have shown that although engagement of either the TCR or glucocorticoid (GC) receptors can individually induce apoptosis in thymocytes, together these signals are mutually antagonistic. This had led to the suggestion that local GC production by thymic epithelial cells, by opposing TCR signaling for apoptosis, provides the basis of the ability of these cells to mediate thymocyte positive selection. In this paper we have examined this possibility directly and shown that highly purified cortical epithelial cells, which have the functional ability to mediate positive selection in reaggregate cultures, do not express mRNA for the key steroidogenic enzyme P405scc. Thus we conclude that the ability of thymic epithelial cells to support positive selection does not rely on their ability to produce GC. However, we find that P450scc mRNA is up-regulated in thymocytes on the initiation of positive selection, raising the possibility that any local protective effect of steroid production is mediated at the level of thymocytes themselves.

Published
1999

47. Predicting outcome after traumatic brain injury: Practical prognostic models based on large cohort of international patients

Author

Perel, P. A., Olldashi, F., Muzha, I., Filipi, N., Lede, R., Copertari, P., Traverso, C., Copertari, A., Vergara, E. A., Montenegro, C., De Huidobro, R. R., Saladino, P., Surt, K., Cialzeta, J., Lazzeri, S., Pinero, G., Ciccioli, F., Videtta, W., Barboza, M. F., Svampa, S., Sciuto, V., Domeniconi, G., Bustamante, M., Waschbusch, M., Gullo, M. P., Drago, D. A., Linares, J. C. A., Camputaro, L., Troccoli, G., Galimberti, H., Tallott, M., Eybner, C., Buchinger, W., Fitzal, S., Mazairac, G., Oleffe, V., Grollinger, T., Delvaux, P., Carlier, L., Braet, V., Jacques, J. -M., De Knoop, D., Nasi, L., Choi, H. K., Schmitt, M., Gentil, A., Nacul, F., Barrios, P. B., Xinkang, C., Hua, L. S., Tian, H. H., Xiaodong, C., Gualteros, W., Otero, A. A., Arango, M., Ciro, J., Jaramillo, H., Gonzalez, I., Gomez, C., Arias, A., Fonseca, M., Mora, C., Cabrera, E. G. L., Betancurth, J. L., Munoz, P., Quinonez, J. A., Castillo, M. E. G., Lopez, O., Yepes, R. P., Cuellar, D. L., Paez, G., Chaves, H. D., Ordonez, P. E., Plata, Riccardo, Pineda, M., Pulido, L. E., Jaramillo, J. S. V., Rebolledo, C., Palma, O., Soler, C., Pastrana, I., Falero, R., Perera, M. D., Garcia, A. A., Oliva, R., Delgado, H. L., Carnero, A. M., Lopez, B. L., Gallardo, A. L., Morales, A. O., Lezcano, H., Ferrer, M. I., Bess, I. Z., Canino, G. R., Ruiz, E. M. P., Cruz, O. G., Svoboda, P., Kantorova, I., Ochmann, J., Scheer, P., Kozumplik, L., Marsova, J., Edelmann, K., Chytra, I., Bosman, R., Andrejsova, H., Pachl, J., Burger, J., Kramar, F., Ulloa, M. I., Gonzalez, L., Daccach, A., Ortega, A., Cevallos, S., Cueva, B. Z., Ochoa, M., Tapia, J. V., Hurtado, J., Wong, M. C. S., Santos, R., Khamis, H., Abaza, A. H., Fekry, A., El Kordy, S., Shawky, T., El-Sayed, H., Khalil, N., Negm, N., Fisal, S., Alamin, M., Shokry, H., Elhusseny, A. Y., Radwan, A., Rashid, M., Gogichaisvili, T., Ingorokva, G., Gongadze, N., Otarashvili, A., Kleist, W., Kalkum, M., Ulrich, P., Andrews, N., Nakos, G., Karavelis, A., Archontakis, G., Myrianthefs, P., Yadav, Y., Yadav, S., Khatri, R., Baghel, A., Husain, M., Jha, D., Chhang, W. H., Dhandhania, M., Fonning, C., Iyengar, S. N., Gupta, S., Ravi, R. R., Bopiah, K. S., Herur, A., Venkataramana, N. K., Satish, A., Bhavadasan, K., Morris, R., Ramesh, S., Dewan, Y., Singh, Y., Bhagchandani, R., Bhagchandani, S., Sethurayar, V. U., Ipe, S., Sreekumar, G., Panigrahi, M., Reddy, A., Khosla, V., Pillay, H., Thomas, N., Sridhar, K., Jose, B., Kurian, N., Praharaj, S., Pillai, S., Ramana, Kiyawat, D., Maheshwari, K., Panikar, D., Chawla, J., Shenoy, S., Raja, A., Rupayana, Y., Reddy, S., Mohan, N., Kelkar, S., Johri, M., Golden, N., Maliawan, S., Fauzi, A., Farouk, U., Fakharian, E., Aramesh, A., Eghtedari, M., Ahmadzadeh, F., Gholami, A., Plunkett, P., Redican, C., Mcmahon, G., Annetta, Maria Giuseppina, Mouchaty, H., Bruzzone, E., Harding, B., Qureshi, M., Idris, Z., Jafri Abdullah, N. C., Ghazali, G., Ghani, A. R. I., Cheah, F., Cabrera, A., Gonzalez, J. L. M., Loria-Castellanos, J., Jackson, S., Hutchinson, R., Komolafe, E., Adeolu, A., Komolafe, M., Adeyemi-Doro, O., Bankole, F., Shehu, B., Danlami, V., Odebode, O., Oluwadiya, K., Sanni, A., Giebel, H., Kumar, S., Jooma, R., Mezquita, J. E., Ovelar, C. O., Portillo, M. G., Rodriguez, D., Balica, L., Oprita, B., Sklerniacof, M., Steflea, L., Bandut, L., Danil, A., Iliescu, R., Ciurea, J., El-Dawlatly, A., Alwatidy, S., Al-Yafi, W., El-Dawlatly, M., Krunic-Protic, R., Janosevic, V., Tan, J., Seah, C., Trenkler, S., Humenansky, M., Stajancova, T., Schwendt, I., Laincz, A., Julius, Z., Maros, S., Firment, J., Cifranicova, M., Saniova, B., Kalig, K., Medekova, S., Wiszt, R., Macuga, I., Hartzenberg, B., Du Plessis, G., Houlie, Z., Nathoo, N., Khumalo, S., Tracey, R., Munoz-Sanchez, A., Francisco Murillo-Cabezas, N. C., Flores-Cordero, J., Rincon- Ferrari, D., Rubi, M., Caler, L., Del Campo, M. M., Laguna, L. B., Nava, J. M., Minguillon, M. A., Lopez, A. M., Ramos-Gomez, L., De La Torre-Prados, V., Pellejero, R., Laloe, V., Mandrella, B., Suganthan, Perera, S., Mahendran, K., Stocker, R., Ludwig, S., Zimmermann, H., Denzler, U., Yutthakasemsunt, S., Kittiwattanagul, W., Piyavechvirat, P., Tapsai, P., Namuang-Jan, A., Chantapimpa, U., Watanachai, C., Subsompon, P., Pussanakawatin, W., Khunjan, P., Tangchitvittaya, S., Nilapong, S., Klangsang, T., Taechakosol, W., Srinat, A., Jerbi, Z., Borsali- Falfoul, N., Rezgui, M., Cakar, N., Ssenyonjo, H., Kobusingye, O., Lomas, G., Yates, D., Lecky, F., Bleetman, A., Baldwin, A., Jenkinson, E., Pantrini, S., Stewart, J., Contractor, N., Roberts, T., Butler, J., Pinto, A., Lee, D., Brayley, N., Robbshaw, K., Dix, C., Graham, S., Pye, S., Green, M., Kellins, A., Moulton, C., Fogg, B., Cottingham, R., Funnell, S., Shanker, U., Summers, C., Malek, L., Ashcroft, C., Powell, J., Moore, S., Buckley, S., Grocutt, M., Chambers, S., Morrice, A., Marshall, H., Harris, J., Matthews, W., Tippet, J., Mardell, S., Macmillan, F., Shaw, A., Luthra, P., Dixon, G., Ahmed, M., Young, M., Mason, S., Loveday, I., Clark, C., Taylor, S., Wilson, P., Ali, K., Greenwood, S., White, M., Perez, R., Eljamel, S., Wasserberg, J., Shale, H., Read, C., Mccarron, J., Pennell, A., Ray, G., Thurston, J., Brown, E., Jaffey, L., Graves, M., Bailey, R., Loveridge, N., Evans, G., Hughes, S., Ahmed, M. K., Richardson, J., Gallagher, C., Odedun, T., Lees, K., Foley, D., Payne, N., Pennycook, A., Griffiths, C., Moore, D., Byrne, D., Dasan, S., Banerjee, Abhishek, Mcguinness, S., Chikhani, C., Zoltie, N., Barlow, I., Stell, I., Hulse, W., Crossley, J., Watkins, L., Dorani, B., Van Viet, T., Plata R., Annetta M. G. (ORCID:0000-0001-7574-1311), Banerjee A., Perel, P. A., Olldashi, F., Muzha, I., Filipi, N., Lede, R., Copertari, P., Traverso, C., Copertari, A., Vergara, E. A., Montenegro, C., De Huidobro, R. R., Saladino, P., Surt, K., Cialzeta, J., Lazzeri, S., Pinero, G., Ciccioli, F., Videtta, W., Barboza, M. F., Svampa, S., Sciuto, V., Domeniconi, G., Bustamante, M., Waschbusch, M., Gullo, M. P., Drago, D. A., Linares, J. C. A., Camputaro, L., Troccoli, G., Galimberti, H., Tallott, M., Eybner, C., Buchinger, W., Fitzal, S., Mazairac, G., Oleffe, V., Grollinger, T., Delvaux, P., Carlier, L., Braet, V., Jacques, J. -M., De Knoop, D., Nasi, L., Choi, H. K., Schmitt, M., Gentil, A., Nacul, F., Barrios, P. B., Xinkang, C., Hua, L. S., Tian, H. H., Xiaodong, C., Gualteros, W., Otero, A. A., Arango, M., Ciro, J., Jaramillo, H., Gonzalez, I., Gomez, C., Arias, A., Fonseca, M., Mora, C., Cabrera, E. G. L., Betancurth, J. L., Munoz, P., Quinonez, J. A., Castillo, M. E. G., Lopez, O., Yepes, R. P., Cuellar, D. L., Paez, G., Chaves, H. D., Ordonez, P. E., Plata, Riccardo, Pineda, M., Pulido, L. E., Jaramillo, J. S. V., Rebolledo, C., Palma, O., Soler, C., Pastrana, I., Falero, R., Perera, M. D., Garcia, A. A., Oliva, R., Delgado, H. L., Carnero, A. M., Lopez, B. L., Gallardo, A. L., Morales, A. O., Lezcano, H., Ferrer, M. I., Bess, I. Z., Canino, G. R., Ruiz, E. M. P., Cruz, O. G., Svoboda, P., Kantorova, I., Ochmann, J., Scheer, P., Kozumplik, L., Marsova, J., Edelmann, K., Chytra, I., Bosman, R., Andrejsova, H., Pachl, J., Burger, J., Kramar, F., Ulloa, M. I., Gonzalez, L., Daccach, A., Ortega, A., Cevallos, S., Cueva, B. Z., Ochoa, M., Tapia, J. V., Hurtado, J., Wong, M. C. S., Santos, R., Khamis, H., Abaza, A. H., Fekry, A., El Kordy, S., Shawky, T., El-Sayed, H., Khalil, N., Negm, N., Fisal, S., Alamin, M., Shokry, H., Elhusseny, A. Y., Radwan, A., Rashid, M., Gogichaisvili, T., Ingorokva, G., Gongadze, N., Otarashvili, A., Kleist, W., Kalkum, M., Ulrich, P., Andrews, N., Nakos, G., Karavelis, A., Archontakis, G., Myrianthefs, P., Yadav, Y., Yadav, S., Khatri, R., Baghel, A., Husain, M., Jha, D., Chhang, W. H., Dhandhania, M., Fonning, C., Iyengar, S. N., Gupta, S., Ravi, R. R., Bopiah, K. S., Herur, A., Venkataramana, N. K., Satish, A., Bhavadasan, K., Morris, R., Ramesh, S., Dewan, Y., Singh, Y., Bhagchandani, R., Bhagchandani, S., Sethurayar, V. U., Ipe, S., Sreekumar, G., Panigrahi, M., Reddy, A., Khosla, V., Pillay, H., Thomas, N., Sridhar, K., Jose, B., Kurian, N., Praharaj, S., Pillai, S., Ramana, Kiyawat, D., Maheshwari, K., Panikar, D., Chawla, J., Shenoy, S., Raja, A., Rupayana, Y., Reddy, S., Mohan, N., Kelkar, S., Johri, M., Golden, N., Maliawan, S., Fauzi, A., Farouk, U., Fakharian, E., Aramesh, A., Eghtedari, M., Ahmadzadeh, F., Gholami, A., Plunkett, P., Redican, C., Mcmahon, G., Annetta, Maria Giuseppina, Mouchaty, H., Bruzzone, E., Harding, B., Qureshi, M., Idris, Z., Jafri Abdullah, N. C., Ghazali, G., Ghani, A. R. I., Cheah, F., Cabrera, A., Gonzalez, J. L. M., Loria-Castellanos, J., Jackson, S., Hutchinson, R., Komolafe, E., Adeolu, A., Komolafe, M., Adeyemi-Doro, O., Bankole, F., Shehu, B., Danlami, V., Odebode, O., Oluwadiya, K., Sanni, A., Giebel, H., Kumar, S., Jooma, R., Mezquita, J. E., Ovelar, C. O., Portillo, M. G., Rodriguez, D., Balica, L., Oprita, B., Sklerniacof, M., Steflea, L., Bandut, L., Danil, A., Iliescu, R., Ciurea, J., El-Dawlatly, A., Alwatidy, S., Al-Yafi, W., El-Dawlatly, M., Krunic-Protic, R., Janosevic, V., Tan, J., Seah, C., Trenkler, S., Humenansky, M., Stajancova, T., Schwendt, I., Laincz, A., Julius, Z., Maros, S., Firment, J., Cifranicova, M., Saniova, B., Kalig, K., Medekova, S., Wiszt, R., Macuga, I., Hartzenberg, B., Du Plessis, G., Houlie, Z., Nathoo, N., Khumalo, S., Tracey, R., Munoz-Sanchez, A., Francisco Murillo-Cabezas, N. C., Flores-Cordero, J., Rincon- Ferrari, D., Rubi, M., Caler, L., Del Campo, M. M., Laguna, L. B., Nava, J. M., Minguillon, M. A., Lopez, A. M., Ramos-Gomez, L., De La Torre-Prados, V., Pellejero, R., Laloe, V., Mandrella, B., Suganthan, Perera, S., Mahendran, K., Stocker, R., Ludwig, S., Zimmermann, H., Denzler, U., Yutthakasemsunt, S., Kittiwattanagul, W., Piyavechvirat, P., Tapsai, P., Namuang-Jan, A., Chantapimpa, U., Watanachai, C., Subsompon, P., Pussanakawatin, W., Khunjan, P., Tangchitvittaya, S., Nilapong, S., Klangsang, T., Taechakosol, W., Srinat, A., Jerbi, Z., Borsali- Falfoul, N., Rezgui, M., Cakar, N., Ssenyonjo, H., Kobusingye, O., Lomas, G., Yates, D., Lecky, F., Bleetman, A., Baldwin, A., Jenkinson, E., Pantrini, S., Stewart, J., Contractor, N., Roberts, T., Butler, J., Pinto, A., Lee, D., Brayley, N., Robbshaw, K., Dix, C., Graham, S., Pye, S., Green, M., Kellins, A., Moulton, C., Fogg, B., Cottingham, R., Funnell, S., Shanker, U., Summers, C., Malek, L., Ashcroft, C., Powell, J., Moore, S., Buckley, S., Grocutt, M., Chambers, S., Morrice, A., Marshall, H., Harris, J., Matthews, W., Tippet, J., Mardell, S., Macmillan, F., Shaw, A., Luthra, P., Dixon, G., Ahmed, M., Young, M., Mason, S., Loveday, I., Clark, C., Taylor, S., Wilson, P., Ali, K., Greenwood, S., White, M., Perez, R., Eljamel, S., Wasserberg, J., Shale, H., Read, C., Mccarron, J., Pennell, A., Ray, G., Thurston, J., Brown, E., Jaffey, L., Graves, M., Bailey, R., Loveridge, N., Evans, G., Hughes, S., Ahmed, M. K., Richardson, J., Gallagher, C., Odedun, T., Lees, K., Foley, D., Payne, N., Pennycook, A., Griffiths, C., Moore, D., Byrne, D., Dasan, S., Banerjee, Abhishek, Mcguinness, S., Chikhani, C., Zoltie, N., Barlow, I., Stell, I., Hulse, W., Crossley, J., Watkins, L., Dorani, B., Van Viet, T., Plata R., Annetta M. G. (ORCID:0000-0001-7574-1311), and Banerjee A.

Abstract

Objective: To develop and validate practical prognostic models for death at 14 days and for death or severe disability six months after traumatic brain injury. Design: Multivariable logistic regression to select variables that were independently associated with two patient outcomes. Two models designed: "basic" model (demographic and clinical variables only) and "CT" model (basic model plus results of computed tomography). The models were subsequently developed for high and low-middle income countries separately. Setting: Medical Research Council (MRC) CRASH Trial. Subjects: 10 008 patients with traumatic brain injury. Models externally validated in a cohort of 8509. Results: The basic model included four predictors: age, Glasgow coma scale, pupil reactivity, and the presence of major extracranial injury. The CT model also included the presence of petechial haemorrhages, obliteration of the third ventricle or basal cisterns, subarachnoid bleeding, midline shift, and non-evacuated haematoma. In the derivation sample the models showed excellent discrimination (C statistic above 0.80). The models showed good calibration graphically. The Hosmer-Lemeshow test also indicated good calibration, except for the CT model in low-middle income countries. External validation for unfavourable outcome at six months in high income countries showed that basic and CT models had good discrimination (C statistic 0.77 for both models) but poorer calibration. Conclusion: Simple prognostic models can be used to obtain valid predictions of relevant outcomes in patients with traumatic brain injury.

Published
2008

48. Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): Randomised placebo-controlled trial

Author

Olldashi, F., Muzha, I., Filipi, N., Lede, R., Copertari, P., Traverso, C., Copertari, A., Vergara, E. A., Montenegro, C., De Huidobro, R. R., Surt, K., Cialzeta, J., Lazzeri, S., Pinero, G., Ciccioli, F., Videtta, W., Barboza, M. F., Svampa, S., Sciuto, V., Domeniconi, G., Bustamante, M., Waschbusch, M., Gullo, M. P., Drago, D. A., Linares, J. C. A., Camputaro, L., Troccoli, G., Galimberti, H., Tallott, M., Eybner, C., Buchinger, W., Fitzal, S., Mazairac, G., Oleffe, V., Grollinger, T., Delvaux, P., Carlier, L., Braet, V., Jacques, J. -M., De Knoop, D., Nasi, L., Choi, H. K., Schmitt, M., Gentil, A., Nacul, F., Barrios, P. B., Xinkang, C., Hua, L. S., Tian, H. H., Xiaodong, C., Gualteros, W., Otero, A. A., Arango, M., Ciro, J., Jaramillo, H., Garcia, G., Gonzalez, I., Gomez, C., Arias, A., Fonseca, M., Mora, C., Cabrera, E. G. L., Betancurth, J. L., Munoz, P., Quinonez, J. A., Castillo, M. E. G., Lopez, O., Yepes, R. P., Cuellar, D. L., Paez, G., Chaves, H. D., Ordonez, P. E., Plata, Riccardo, Pineda, M., Pulido, L. E., Jaramillo, J. S. V., Rebolledo, C., Palma, O., Soler, C., Pastrana, I., Falero, R., Perera, M. D., Garcia, A. A., Oliva, R., Delgado, H. L., Carnero, A. M., Lopez, B. L., Gallardo, A. L., Morales, A. O., Lezcano, H., Ferrer, M. I., Bess, I. Z., Canino, G. R., Ruiz, E. M. P., Cruz, O. G., Svoboda, P., Kantorova, I., Ochmann, J., Scheer, P., Kozumplik, L., Marsova, J., Edelmann, K., Chytra, I., Bosman, R., Andrejsova, H., Pachl, J., Burger, J., Kramar, F., Ulloa, M. I., Gonzalez, L., Daccach, A., Ortega, A., Cevallos, S., Cueva, B. Z., Ochoa, M., Tapia, J. V., Hurtado, J., Wong, M. C. S., Santos, R., Khamis, H., Abaza, A. H., Fekry, A., El Kordy, S., Shawky, T., El-Sayed, H., Khalil, N., Negm, N., Fisal, S., Shokry, H., Alamin, M., Elhusseny, A. Y., Radwan, A., Rashid, M., Gogichaisvili, T., Ingorokva, G., Gongadze, N., Otarashvili, A., Kleist, W., Kalkum, M., Ulrich, P., Andrews, N., Nakos, G., Karavelis, A., Archontakis, G., Myrianthefs, P., Yadav, Y., Yadav, S., Khatri, R., Baghel, A., Husain, M., Jha, D., Hoong Chhang, W., Dhandhania, M., Fonning, C., Iyengar, S. N., Gupta, S., Ravi, R. R., Bopiah, K. S., Herur, A., Venkataramana, N. K., Satish, A., Bhavadasan, K., Morris, R., Ramesh, S., Dewan, Y., Singh, Y., Bhagchandani, R., Bhagchandani, S., Sethurayar, V., Ipe, S., Sreekumar, G., Panigrahi, M., Reddy, A., Khosla, V., Pillay, H., Thomas, N., Sridhar, K., Jose, B., Kurian, N., Praharaj, S., Pillai, S., Ramana, Kiyawat, D., Maheshwari, K., Panikar, D., Chawla, J., Shenoy, S., Raja, A., Rupayana, Y., Reddy, S., Mohan, N., Kelkar, S., Johri, M., Golden, N., Maliawan, S., Fauzi, A., Farouk, U., Fakharian, E., Aramesh, A., Eghtedari, M., Ahmadzadeh, F., Gholami, A., Plunkett, P., Redican, C., Mcmahon, G., Annetta, Maria Giuseppina, Mouchaty, H., Bruzzone, E., Harding, B., Qureshi, M., Idris, Z., Abdullah, J., Ghazali, G., Ghani, A., Cheah, F., Gonzalez, J., Loria-Castellanos, J., Jackson, S., Hutchinson, R., Komolafe, E., Adeolu, A., Komolafe, M., Adeyemi-Doro, O., Bankole, F., Shehu, B., Danlami, V., Odebode, O., Oluwadiya, K., Sanni, A., Giebel, H., Kumar, S., Jooma, R., Mezquita, J., Ortiz Ovelar, C., Gonzales-Portillo, M., Rodriguez, D., Balica, L., Oprita, B., Sklerniacof, M., Steflea, L., Bandut, L., Danil, A., Iliescu, R., Ciurea, J., El-Dawlatly, A., Alwatidy, S., Al-Yafi, W., El-Dawlatly, M., Krunic-Protic, R., Janosevic, V., Tan, J., Seah, C., Trenkler, S., Humenansky, M., Stajancova, T., Schwendt, I., Laincz, A., Julius, Z., Maros, S., Firment, J., Cifranicova, M., Saniova, B., Kalig, K., Medekova, S., Wiszt, R., Macsuga, I., Hartzenberg, B., Du Plessis, G., Houlie, Z., Nathoo, N., Khumalo, S., Tracey, R., Munoz-Sanchez, A., Murillo-Cabezas, F., Flores-Cordero, J., Rincon-Ferrari, D., Rubi, M., Caler, L., Del Campo, M., Laguna, L., Manuel Nava, J., Minguillon, M., Lopez, A., Ramos-Gomez, L., De La Torre-Prados, V., Pellejero, R., Laloe, V., Mandrella, B., Suganthan, Perera, S., Mahendran, K., Stocker, R., Ludwig, S., Zimmermann, H., Denzler, U., Yutthakasemsunt, S., Kittiwattanagul, W., Watanachai, C., Subsompon, P., Pussanakawatin, W., Khunjan, P., Tangchitvittaya, S., Nilapong, S., Klangsang, T., Taechakosol, W., Srinat, A., Jerbi, Z., Borsali-Falfoul, N., Rezgui, M., Cakar, N., Ssenyonjo, H., Kobusingye, O., Lomas, G., Yates, D., Lecky, F., Bleetman, A., Baldwin, A., Jenkinson, E., Pantrini, S., Stewart, J., Contractor, N., Roberts, T., Butler, J., Pinto, A., Lee, D., Brayley, N., Robbshaw, K., Dix, C., Graham, S., Pye, S., Green, M., Kellins, A., Moulton, C., Fogg, B., Cottingham, R., Funnell, S., Shanker, U., Summers, C., Malek, L., Ashcroft, C., Powell, J., Moore, S., Buckley, S., Grocutt, M., Chambers, S., Morrice, A., Marshall, H., Harris, J., Matthews, W., Tippet, J., Mardell, S., Macmillan, F., Shaw, A., Luthra, P., Dixon, G., Ahmed, M., Young, M., Mason, S., Loveday, I., Clark, C., Taylor, S., Wilson, P., Ali, K., Greenwood, S., White, M., Perez, R., Eljamel, S., Wasserberg, J., Shale, H., Read, C., Mccarron, J., Pennell, A., Ray, G., Thurston, J., Brown, E., Jaffey, L., Graves, M., Bailey, R., Loveridge, N., Evans, G., Hughes, S., Richardson, J., Gallagher, C., Odedun, T., Lees, K., Foley, D., Payne, N., Pennycook, A., Griffiths, C., Moore, D., Byrne, D., Dasan, S., Banerjee, Abhishek, Mcguinness, S., Chikhani, C., Zoltie, N., Barlow, I., Stell, I., Hulse, W., Crossley, J., Watkins, L., Dorani, B., Vanviet, T., Saladino, P., Cabrera, A., Baigent, C., Bracken, M., Chadwick, D., Curley, K., Duley, L., Farrell, B., Haegi, M., Nickson, G., Peto, R., Pickard, J., Roberts, I., Sandercock, P., Teasdale, G., Collins, R., Haines, S., Macmahon, S., Warlow, C., Edwards, P., Ritchie, N., Shakur, H., Ramos, M., Barnetson, L., Fernandes, J., Tooth, D., Free, C., Narayanan, L., Collander, J., Abernethy, J., Bardswell, J., Mashru, R., Godward, C., Afolabi, L., Ritchie, A., Hosford, T., Collingwood, A., Massey, S., Plata R., Annetta M. (ORCID:0000-0001-7574-1311), Banerjee A., Olldashi, F., Muzha, I., Filipi, N., Lede, R., Copertari, P., Traverso, C., Copertari, A., Vergara, E. A., Montenegro, C., De Huidobro, R. R., Surt, K., Cialzeta, J., Lazzeri, S., Pinero, G., Ciccioli, F., Videtta, W., Barboza, M. F., Svampa, S., Sciuto, V., Domeniconi, G., Bustamante, M., Waschbusch, M., Gullo, M. P., Drago, D. A., Linares, J. C. A., Camputaro, L., Troccoli, G., Galimberti, H., Tallott, M., Eybner, C., Buchinger, W., Fitzal, S., Mazairac, G., Oleffe, V., Grollinger, T., Delvaux, P., Carlier, L., Braet, V., Jacques, J. -M., De Knoop, D., Nasi, L., Choi, H. K., Schmitt, M., Gentil, A., Nacul, F., Barrios, P. B., Xinkang, C., Hua, L. S., Tian, H. H., Xiaodong, C., Gualteros, W., Otero, A. A., Arango, M., Ciro, J., Jaramillo, H., Garcia, G., Gonzalez, I., Gomez, C., Arias, A., Fonseca, M., Mora, C., Cabrera, E. G. L., Betancurth, J. L., Munoz, P., Quinonez, J. A., Castillo, M. E. G., Lopez, O., Yepes, R. P., Cuellar, D. L., Paez, G., Chaves, H. D., Ordonez, P. E., Plata, Riccardo, Pineda, M., Pulido, L. E., Jaramillo, J. S. V., Rebolledo, C., Palma, O., Soler, C., Pastrana, I., Falero, R., Perera, M. D., Garcia, A. A., Oliva, R., Delgado, H. L., Carnero, A. M., Lopez, B. L., Gallardo, A. L., Morales, A. O., Lezcano, H., Ferrer, M. I., Bess, I. Z., Canino, G. R., Ruiz, E. M. P., Cruz, O. G., Svoboda, P., Kantorova, I., Ochmann, J., Scheer, P., Kozumplik, L., Marsova, J., Edelmann, K., Chytra, I., Bosman, R., Andrejsova, H., Pachl, J., Burger, J., Kramar, F., Ulloa, M. I., Gonzalez, L., Daccach, A., Ortega, A., Cevallos, S., Cueva, B. Z., Ochoa, M., Tapia, J. V., Hurtado, J., Wong, M. C. S., Santos, R., Khamis, H., Abaza, A. H., Fekry, A., El Kordy, S., Shawky, T., El-Sayed, H., Khalil, N., Negm, N., Fisal, S., Shokry, H., Alamin, M., Elhusseny, A. Y., Radwan, A., Rashid, M., Gogichaisvili, T., Ingorokva, G., Gongadze, N., Otarashvili, A., Kleist, W., Kalkum, M., Ulrich, P., Andrews, N., Nakos, G., Karavelis, A., Archontakis, G., Myrianthefs, P., Yadav, Y., Yadav, S., Khatri, R., Baghel, A., Husain, M., Jha, D., Hoong Chhang, W., Dhandhania, M., Fonning, C., Iyengar, S. N., Gupta, S., Ravi, R. R., Bopiah, K. S., Herur, A., Venkataramana, N. K., Satish, A., Bhavadasan, K., Morris, R., Ramesh, S., Dewan, Y., Singh, Y., Bhagchandani, R., Bhagchandani, S., Sethurayar, V., Ipe, S., Sreekumar, G., Panigrahi, M., Reddy, A., Khosla, V., Pillay, H., Thomas, N., Sridhar, K., Jose, B., Kurian, N., Praharaj, S., Pillai, S., Ramana, Kiyawat, D., Maheshwari, K., Panikar, D., Chawla, J., Shenoy, S., Raja, A., Rupayana, Y., Reddy, S., Mohan, N., Kelkar, S., Johri, M., Golden, N., Maliawan, S., Fauzi, A., Farouk, U., Fakharian, E., Aramesh, A., Eghtedari, M., Ahmadzadeh, F., Gholami, A., Plunkett, P., Redican, C., Mcmahon, G., Annetta, Maria Giuseppina, Mouchaty, H., Bruzzone, E., Harding, B., Qureshi, M., Idris, Z., Abdullah, J., Ghazali, G., Ghani, A., Cheah, F., Gonzalez, J., Loria-Castellanos, J., Jackson, S., Hutchinson, R., Komolafe, E., Adeolu, A., Komolafe, M., Adeyemi-Doro, O., Bankole, F., Shehu, B., Danlami, V., Odebode, O., Oluwadiya, K., Sanni, A., Giebel, H., Kumar, S., Jooma, R., Mezquita, J., Ortiz Ovelar, C., Gonzales-Portillo, M., Rodriguez, D., Balica, L., Oprita, B., Sklerniacof, M., Steflea, L., Bandut, L., Danil, A., Iliescu, R., Ciurea, J., El-Dawlatly, A., Alwatidy, S., Al-Yafi, W., El-Dawlatly, M., Krunic-Protic, R., Janosevic, V., Tan, J., Seah, C., Trenkler, S., Humenansky, M., Stajancova, T., Schwendt, I., Laincz, A., Julius, Z., Maros, S., Firment, J., Cifranicova, M., Saniova, B., Kalig, K., Medekova, S., Wiszt, R., Macsuga, I., Hartzenberg, B., Du Plessis, G., Houlie, Z., Nathoo, N., Khumalo, S., Tracey, R., Munoz-Sanchez, A., Murillo-Cabezas, F., Flores-Cordero, J., Rincon-Ferrari, D., Rubi, M., Caler, L., Del Campo, M., Laguna, L., Manuel Nava, J., Minguillon, M., Lopez, A., Ramos-Gomez, L., De La Torre-Prados, V., Pellejero, R., Laloe, V., Mandrella, B., Suganthan, Perera, S., Mahendran, K., Stocker, R., Ludwig, S., Zimmermann, H., Denzler, U., Yutthakasemsunt, S., Kittiwattanagul, W., Watanachai, C., Subsompon, P., Pussanakawatin, W., Khunjan, P., Tangchitvittaya, S., Nilapong, S., Klangsang, T., Taechakosol, W., Srinat, A., Jerbi, Z., Borsali-Falfoul, N., Rezgui, M., Cakar, N., Ssenyonjo, H., Kobusingye, O., Lomas, G., Yates, D., Lecky, F., Bleetman, A., Baldwin, A., Jenkinson, E., Pantrini, S., Stewart, J., Contractor, N., Roberts, T., Butler, J., Pinto, A., Lee, D., Brayley, N., Robbshaw, K., Dix, C., Graham, S., Pye, S., Green, M., Kellins, A., Moulton, C., Fogg, B., Cottingham, R., Funnell, S., Shanker, U., Summers, C., Malek, L., Ashcroft, C., Powell, J., Moore, S., Buckley, S., Grocutt, M., Chambers, S., Morrice, A., Marshall, H., Harris, J., Matthews, W., Tippet, J., Mardell, S., Macmillan, F., Shaw, A., Luthra, P., Dixon, G., Ahmed, M., Young, M., Mason, S., Loveday, I., Clark, C., Taylor, S., Wilson, P., Ali, K., Greenwood, S., White, M., Perez, R., Eljamel, S., Wasserberg, J., Shale, H., Read, C., Mccarron, J., Pennell, A., Ray, G., Thurston, J., Brown, E., Jaffey, L., Graves, M., Bailey, R., Loveridge, N., Evans, G., Hughes, S., Richardson, J., Gallagher, C., Odedun, T., Lees, K., Foley, D., Payne, N., Pennycook, A., Griffiths, C., Moore, D., Byrne, D., Dasan, S., Banerjee, Abhishek, Mcguinness, S., Chikhani, C., Zoltie, N., Barlow, I., Stell, I., Hulse, W., Crossley, J., Watkins, L., Dorani, B., Vanviet, T., Saladino, P., Cabrera, A., Baigent, C., Bracken, M., Chadwick, D., Curley, K., Duley, L., Farrell, B., Haegi, M., Nickson, G., Peto, R., Pickard, J., Roberts, I., Sandercock, P., Teasdale, G., Collins, R., Haines, S., Macmahon, S., Warlow, C., Edwards, P., Ritchie, N., Shakur, H., Ramos, M., Barnetson, L., Fernandes, J., Tooth, D., Free, C., Narayanan, L., Collander, J., Abernethy, J., Bardswell, J., Mashru, R., Godward, C., Afolabi, L., Ritchie, A., Hosford, T., Collingwood, A., Massey, S., Plata R., Annetta M. (ORCID:0000-0001-7574-1311), and Banerjee A.

Abstract

Background Corticosteroids have been used to treat head injuries for more than 30 years. In 1997, findings of a systematic review suggested that these drugs reduce risk of death by 1-2%. The CRASH trial—a multicentre international collaboration—aimed to confirm or refute such an effect by recruiting 20 000 patients. In May, 2004, the data monitoring committee disclosed the unmasked results to the steering committee, which stopped recruitment. Methods 10 008 adults with head injury and a Glasgow coma score (GCS) of 14 or less within 8 h of injury were randomly allocated 48 h infusion of corticosteroids (methylprednisolone) or placebo. Primary outcomes were death within 2 weeks of injury and death or disability at 6 months. Prespecified subgroup analyses were based on injury severity (GCS) at randomisation and on time from injury to randomisation. Analysis was by intention to treat. Effects on outcomes within 2 weeks of randomisation are presented in this report. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN74459797. Findings Compared with placebo, the risk of death from all causes within 2 weeks was higher in the group allocated corticosteroids (1052 [21·1%] vs 893 [17·9%] deaths; relative risk 1·18 [95% CI 1·09-1·27]; p=0·0001). The relative increase in deaths due to corticosteroids did not differ by injury severity (p=0·22) or time since injury (p=0·05). Interpretation Our results show there is no reduction in mortality with methylprednisolone in the 2 weeks after head injury. The cause of the rise in risk of death within 2 weeks is unclear.

Published
2004

49. Developmental regulation of bcl-2 expression in the thymus

Author

Moore, N. C., graham anderson, Williams, G. T., Owen, J. J. T., and Jenkinson, E. J.

Subjects
Mice, Inbred BALB C, Base Sequence, T-Lymphocytes, Molecular Sequence Data, Receptors, Antigen, T-Cell, Gene Expression, Apoptosis, Cell Differentiation, Thymus Gland, Polymerase Chain Reaction, Mice, Proto-Oncogene Proteins c-bcl-2, Proto-Oncogene Proteins, Animals, RNA, Messenger, Research Article
Abstract

An important factor in shaping the T-cell receptor (TcR) repertoire during thymocyte development is the susceptibility of double-positive (CD4+ CD8+) thymocytes to induction of apoptosis (negative selection) when the TcR is engaged by 'self'-antigens. Recent evidence has suggested that this susceptibility to apoptosis may be influenced by the expression of bcl-2, a proto-oncogene known to increase the resistance to apoptosis in various cell systems. Using a semi-quantitative polymerase chain reaction (PCR) technique in conjunction with staged embryonic material and purified thymocyte subpopulations we have investigated patterns of bcl-2 expression during normal T-cell development. Our results show that while bcl-2 alpha gene expression is readily detectable in immature CD3-CD4-CD8- thymocytes and in mature single-positive TcRhi cells, it is drastically reduced in TcR negative double-positive (CD3- CD4+ CD8+) cortical thymocytes of intermediate maturity. Careful mapping of bcl-2 alpha re-expression in relation to the onset of TcR expression within the population of embryonic thymocytes indicates that bcl-2 alpha is up-regulated as soon as TcR molecules are expressed on the surface of CD4+ CD8+ thymocytes. Therefore, thymocytes susceptible to apoptosis on TcR ligation express bcl-2 alpha mRNA suggesting that changing levels of bcl-2 expression are unlikely to be the only determinant regulating susceptibility to apoptosis in the thymus. The possible implications of these changes in bcl-2 expression regarding other facets of thymocyte development will be discussed.

Published
1994

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