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1. New orphan disease therapies from the proteome of industrial plasma processing waste- a treatment for aceruloplasminemia

Author

Zanardi, A, Nardini, I, Raia, S, Conti, A, Ferrini, B, D'Adamo, P, Gilberti, E, Depalma, G, Belloli, S, Monterisi, C, Coliva, A, Rainone, P, Moresco, R, Mori, F, Zurlo, G, Scali, C, Natali, L, Pancanti, A, Giovacchini, P, Magherini, G, Tovani, G, Salvini, L, Cicaloni, V, Tinti, C, Tinti, L, Lana, D, Magni, G, Giovannini, M, Gringeri, A, Caricasole, A, Alessio, M, Zanardi A., Nardini I., Raia S., Conti A., Ferrini B., D'Adamo P., Gilberti E., DePalma G., Belloli S., Monterisi C., Coliva A., Rainone P., Moresco R. M., Mori F., Zurlo G., Scali C., Natali L., Pancanti A., Giovacchini P., Magherini G., Tovani G., Salvini L., Cicaloni V., Tinti C., Tinti L., Lana D., Magni G., Giovannini M. G., Gringeri A., Caricasole A., Alessio M., Zanardi, A, Nardini, I, Raia, S, Conti, A, Ferrini, B, D'Adamo, P, Gilberti, E, Depalma, G, Belloli, S, Monterisi, C, Coliva, A, Rainone, P, Moresco, R, Mori, F, Zurlo, G, Scali, C, Natali, L, Pancanti, A, Giovacchini, P, Magherini, G, Tovani, G, Salvini, L, Cicaloni, V, Tinti, C, Tinti, L, Lana, D, Magni, G, Giovannini, M, Gringeri, A, Caricasole, A, Alessio, M, Zanardi A., Nardini I., Raia S., Conti A., Ferrini B., D'Adamo P., Gilberti E., DePalma G., Belloli S., Monterisi C., Coliva A., Rainone P., Moresco R. M., Mori F., Zurlo G., Scali C., Natali L., Pancanti A., Giovacchini P., Magherini G., Tovani G., Salvini L., Cicaloni V., Tinti C., Tinti L., Lana D., Magni G., Giovannini M. G., Gringeri A., Caricasole A., and Alessio M.

Abstract

Plasma-derived therapeutic proteins are produced through an industrial fractionation process where proteins are purified from individual intermediates, some of which remain unused and are discarded. Relatively few plasma-derived proteins are exploited clinically, with most of available plasma being directed towards the manufacture of immunoglobulin and albumin. Although the plasma proteome provides opportunities to develop novel protein replacement therapies, particularly for rare diseases, the high cost of plasma together with small patient populations impact negatively on the development of plasma-derived orphan drugs. Enabling therapeutics development from unused plasma fractionation intermediates would therefore constitute a substantial innovation. To this objective, we characterized the proteome of unused plasma fractionation intermediates and prioritized proteins for their potential as new candidate therapies for human disease. We selected ceruloplasmin, a plasma ferroxidase, as a potential therapy for aceruloplasminemia, an adult-onset ultra-rare neurological disease caused by iron accumulation as a result of ceruloplasmin mutations. Intraperitoneally administered ceruloplasmin, purified from an unused plasma fractionation intermediate, was able to prevent neurological, hepatic and hematological phenotypes in ceruloplasmin-deficient mice. These data demonstrate the feasibility of transforming industrial waste plasma fraction into a raw material for manufacturing of new candidate proteins for replacement therapies, optimizing plasma use and reducing waste generation.

Published
2024

2. Research considerations for prospective studies of patients with coma and disorders of consciousness

Author

Tinti, L, Lawson, T, Molteni, E, Kondziella, D, Rass, V, Sharshar, T, Bodien, Y, Giacino, J, Mayer, S, Amiri, M, Muehlschlegel, S, Venkatasubba Rao, C, Vespa, P, Menon, D, Citerio, G, Helbok, R, Mcnett, M, Agarwal, S, Aiyagari, V, Akbari, Y, Albertson, A, Alexander, S, Alexandrov, A, Alkhachroum, A, Al-Mufti, F, Appavu, B, Gebrewold, M, Ayounb, M, Badenes, R, Bader, M, Badjiata, N, Balu, R, Barlow, B, Barra, M, Beekman, R, Beghi, E, Beqiri, E, Berlin, T, Bilotta, F, Bleck, T, Boerwinkle, V, Boly, M, Bonnel, A, Brazzi, L, Brown, E, Bulic, S, Caceres, E, Caceres, A, Cafiero, T, Carroll, E, Cediel, E, Chou, S, Claassen, J, Condie, C, Conti, A, Cosmas, K, Costa, P, Creutzfeldt, C, Dangayach, N, Dauri, M, Debicki, D, Degeorgia, M, Der-Nigoghossian, C, Desai, M, Dhar, R, Diringer, M, Durr, E, Edlow, B, Ercole, A, Estraneo, A, Falcone, G, Farrokh, S, Ferguson, A, Fernandez-Espejo, D, Fink, E, Fins, J, Foreman, B, Franchi, F, Frontera, J, Ganesan, R, Gaspard, N, Ghavam, A, Gibbons, C, Gilmore, E, Glustein, C, Gosseries, O, Green, T, Greer, D, Guanci, M, Gupta, D, Hahn, C, Hakimi, R, Hammond, F, Hanley, D, Hartings, J, Hassan, A, Hemphill, C, Da Cunha, A, Hinson, H, Hirsch, K, Hocker, S, Hu, P, Hu, X, Human, T, Hwang, D, Illes, J, Jaffa, M, James, M, Janas, A, Johnson, S, Jones, M, Jox, R, Kalanuria, A, Keller, E, Kennedy, L, Kennelly, M, Keogh, M, Kim, J, Kim, K, Kirsch, H, Kirschen, M, Ko, N, Kreitzer, N, Kromm, J, Kumar, A, Kurtz, P, Laureys, S, Lejeune, N, Lewis, A, Liang, J, Ling, G, Livesay, S, Luppi, A, Macdonald, J, Maddux, C, Mahanes, D, Mainali, S, Maldonado, N, Ribeiro, R, Mascia, L, Massimini, M, Mathur, R, Mccredie, V, Mejia-Mantilla, J, Mendoza, M, Meyfroidt, G, Mijangos, J, Moberg, D, Moheet, A, Montalenti, E, Monti, M, Morrison, C, Munar, M, Murtaugh, B, Naccache, L, Nagayama, M, Nairon, E, Nakagawa, T, Naldi, A, Narenthiran, G, Natarajan, G, Nemetsky, E, Newcombe, V, Nielsen, N, Niznick, N, Noronha-Falcão, F, Nyquist, P, Olson, D, Othman, M, Owen, A, Padayachy, L, Pajoumand, M, Park, S, Pergakis, M, Perry, H, Polizzotto, L, Pouratian, N, Spivack, M, Prisco, L, Provencio, J, Puglises, F, Puybasset, L, Rao, C, Rasmussen, L, Rasulo, F, Ray, B, Ricci, Z, Richardson, R, Shinotsuka, C, Robba, C, Robertson, C, Rohaut, B, Rolston, J, Romagnoli, S, Rosanova, M, Rosenthal, E, Rowe, S, Rubin, M, Russell, M, Silva, G, Sanz, L, Sarasso, S, Sarwal, A, Schiff, N, Schnakers, C, Seder, D, Shah, V, Shapiro-Rosenbaubm, A, Shapshak, A, Sharma, K, Shutter, L, Sitt, J, Slomine, B, Smetana, K, Smielewski, P, Smith, W, Stamatakis, E, Steinberg, A, Stevens, R, Suarez, J, Sung, G, Sussman, B, Taran, S, Mazzeo, A, Thibaut, A, Thompson, D, Threlkeld, Z, Toker, D, Torbey, M, Tosto, J, Trevick, S, Tsaousi, G, Turgeon, A, Udy, A, Varelas, P, Videtta, W, Voss, H, Vox, F, Wagner, A, Wahlster, S, Wainwright, M, Whyte, J, Witherspoon, B, Yakhkind, A, Yeager, S, Young, M, Zafar, S, Zafonte, R, Zahuranec, D, Zammit, C, Zhang, B, Ziai, W, Zimmerman, L, Zink, E, Tinti, Lorenzo, Lawson, Thomas, Molteni, Erika, Kondziella, Daniel, Rass, Verena, Sharshar, Tarek, Bodien, Yelena G, Giacino, Joseph T, Mayer, Stephan A, Amiri, Moshgan, Muehlschlegel, Susanne, Venkatasubba Rao, Chethan P, Vespa, Paul M, Menon, David K, Citerio, Giuseppe, Helbok, Raimund, McNett, Molly, Agarwal, Sachin, Aiyagari, Venkatesh, Akbari, Yama, Albertson, Asher, Alexander, Sheila, Alexandrov, Anne, Alkhachroum, Ayham, Al-Mufti, Fawaz, Amiri, Moshagan, Appavu, Brian, Gebrewold, Meron Awraris, Ayounb, Marc, Badenes, Rafael, Bader, Mary Kay, Badjiata, Neeraj, Balu, Ram, Barlow, Brooke, Barra, Megan, Beekman, Rachel, Beghi, Ettore, Beqiri, Erta, Berlin, Tracey, Bilotta, Federico, Bleck, Thomas, Bodien, Yelena, Boerwinkle, Varina, Boly, Melanie, Bonnel, Alexandra, Brazzi, Luca, Brown, Emery, Bulic, Sebina, Caceres, Eder, Caceres, Adrian, Cafiero, Tullio, Carroll, Elizabeth, Cediel, Emilio G, Chou, Sherry, Claassen, Jan, Condie, Chad, Conti, Alfredo, Cosmas, Katie, Costa, Paolo, Creutzfeldt, Claire, Dangayach, Neha, Dauri, Mario, Debicki, Derek, DeGeorgia, Michael, Der-Nigoghossian, Caroline, Desai, Masoom, Dhar, Rajat, Diringer, Michael, Durr, Emily, Edlow, Brian, Ercole, Ari, Estraneo, Anna, Falcone, Guido, Farrokh, Salia, Ferguson, Adam, Fernandez-Espejo, Davinia, Fink, Ericka, Fins, Joseph, Foreman, Brandon, Franchi, Federico, Frontera, Jennifer, Ganesan, Rishi, Gaspard, Nicolas, Ghavam, Ahmeneh, Giacino, Joseph, Gibbons, Christie, Gilmore, Emily, Glustein, Chavie, Gosseries, Olivia, Green, Theresa, Greer, David, Guanci, Mary, Gupta, Deepak, Hahn, Cecil, Hakimi, Ryan, Hammond, Flora, Hanley, Daniel F, Hartings, Jed, Hassan, Ahmed, Hemphill, Claude, Da Cunha, Arthur Henrique Galvão Bruno, Hinson, Holly, Hirsch, Karen, Hocker, Sarah, Hu, Peter, Hu, Xiao, Human, Theresa, Hwang, David, Illes, Judy, Jaffa, Matthew, James, Michael L, Janas, Anna, Johnson, Susan, Jones, Morgan, Jox, Ralf J, Kalanuria, Atul, Keller, Emanuela, Kennedy, Lori, Kennelly, Megan, Keogh, Maggie, Kim, Jenn, Kim, Keri, Kirsch, Hannah, Kirschen, Matthew, Ko, Nerissa, Kreitzer, Natalie, Kromm, Julie, Kumar, Abhay, Kurtz, Pedro, Laureys, Steven, Lejeune, Nicolas, Lewis, Ariane, Liang, John, Ling, Geoffrey, Livesay, Sarah, Luppi, Andrea, MacDonald, Jennifer, Maddux, Craig, Mahanes, Dea, Mainali, Shraddha, Maldonado, Nelson, Ribeiro, Rennan Martins, Mascia, Luciana, Massimini, Marcello, Mathur, Rohan, Mayer, Stephan, McCredie, Victoria, Mejia-Mantilla, Jorge, Mendoza, Michael, Menon, David, Meyfroidt, Geert, Mijangos, Julio, Moberg, Dick, Moheet, Asma, Montalenti, Elisa, Monti, Martin, Morrison, Chris, Munar, Marina, Murtaugh, Brooke, Naccache, Lionel, Nagayama, Masao, Nairon, Emerson, Nakagawa, Thomas, Naldi, Andrea, Narenthiran, Ganesalingam, Natarajan, Girija, Nemetsky, Esther, Newcombe, Virginia, Nielsen, Niklas, Niznick, Naomi, Noronha-Falcão, Filipa, Nyquist, Paul, Olson, DaiWai, Othman, Marwan, Owen, Adrian, Padayachy, Llewellyn, Pajoumand, Mehrnaz, Park, Soojin, Pergakis, Melissa, Perry, Heidi, Polizzotto, Len, Pouratian, Nader, Spivack, Marilyn Price, Prisco, Lara, Provencio, Javier, Puglises, Francesco, Puybasset, Louis, Rao, Chethan, Rasmussen, Lindsay, Rasulo, Frank, Ray, Bappaditya, Ricci, Zaccaria, Richardson, Risa, Shinotsuka, Cassia Righy, Robba, Chiara, Robertson, Courtney, Rohaut, Benjamin, Rolston, John, Romagnoli, Stefano, Rosanova, Mario, Rosenthal, Eric, Rowe, Shaun, Rubin, Michael, Russell, Mary Beth, Silva, Gisele Sampaio, Sanz, Leandro, Sarasso, Simone, Sarwal, Aarti, Schiff, Nicolas, Schnakers, Caroline, Seder, David, Shah, Vishank Arun, Shapiro-Rosenbaubm, Amy, Shapshak, Angela, Sharma, Kartavya, Sharma, Kumar Ajay, Shutter, Lori, Sitt, Jacobo, Slomine, Beth, Smetana, Keaton, Smielewski, Peter, Smith, Wade, Stamatakis, Emmanuel, Steinberg, Alexis, Stevens, Robert, Suarez, Jose, Sung, Gene, Sussman, Bethany, Taran, Shaurya, Mazzeo, Anna Teresa, Thibaut, Aurore, Thompson, David, Threlkeld, Zachary, Toker, Daniel, Torbey, Michel, Tosto, Jenna, Trevick, Stephen, Tsaousi, Georgia, Turgeon, Alexis, Udy, Andrew, Varelas, Panos, Vespa, Paul, Videtta, Walter, Voss, Henning, Vox, Ford, Wagner, Amy, Wahlster, Sarah, Wainwright, Mark, Whyte, John, Witherspoon, Briana, Yakhkind, Aleksandra (Sasha), Yeager, Susan, Young, Michael, Zafar, Sahar, Zafonte, Ross, Zahuranec, Darin, Zammit, Chris, Zhang, Bei, Ziai, Wendy, Zimmerman, Lara, Zink, Elizabeth, Tinti, L, Lawson, T, Molteni, E, Kondziella, D, Rass, V, Sharshar, T, Bodien, Y, Giacino, J, Mayer, S, Amiri, M, Muehlschlegel, S, Venkatasubba Rao, C, Vespa, P, Menon, D, Citerio, G, Helbok, R, Mcnett, M, Agarwal, S, Aiyagari, V, Akbari, Y, Albertson, A, Alexander, S, Alexandrov, A, Alkhachroum, A, Al-Mufti, F, Appavu, B, Gebrewold, M, Ayounb, M, Badenes, R, Bader, M, Badjiata, N, Balu, R, Barlow, B, Barra, M, Beekman, R, Beghi, E, Beqiri, E, Berlin, T, Bilotta, F, Bleck, T, Boerwinkle, V, Boly, M, Bonnel, A, Brazzi, L, Brown, E, Bulic, S, Caceres, E, Caceres, A, Cafiero, T, Carroll, E, Cediel, E, Chou, S, Claassen, J, Condie, C, Conti, A, Cosmas, K, Costa, P, Creutzfeldt, C, Dangayach, N, Dauri, M, Debicki, D, Degeorgia, M, Der-Nigoghossian, C, Desai, M, Dhar, R, Diringer, M, Durr, E, Edlow, B, Ercole, A, Estraneo, A, Falcone, G, Farrokh, S, Ferguson, A, Fernandez-Espejo, D, Fink, E, Fins, J, Foreman, B, Franchi, F, Frontera, J, Ganesan, R, Gaspard, N, Ghavam, A, Gibbons, C, Gilmore, E, Glustein, C, Gosseries, O, Green, T, Greer, D, Guanci, M, Gupta, D, Hahn, C, Hakimi, R, Hammond, F, Hanley, D, Hartings, J, Hassan, A, Hemphill, C, Da Cunha, A, Hinson, H, Hirsch, K, Hocker, S, Hu, P, Hu, X, Human, T, Hwang, D, Illes, J, Jaffa, M, James, M, Janas, A, Johnson, S, Jones, M, Jox, R, Kalanuria, A, Keller, E, Kennedy, L, Kennelly, M, Keogh, M, Kim, J, Kim, K, Kirsch, H, Kirschen, M, Ko, N, Kreitzer, N, Kromm, J, Kumar, A, Kurtz, P, Laureys, S, Lejeune, N, Lewis, A, Liang, J, Ling, G, Livesay, S, Luppi, A, Macdonald, J, Maddux, C, Mahanes, D, Mainali, S, Maldonado, N, Ribeiro, R, Mascia, L, Massimini, M, Mathur, R, Mccredie, V, Mejia-Mantilla, J, Mendoza, M, Meyfroidt, G, Mijangos, J, Moberg, D, Moheet, A, Montalenti, E, Monti, M, Morrison, C, Munar, M, Murtaugh, B, Naccache, L, Nagayama, M, Nairon, E, Nakagawa, T, Naldi, A, Narenthiran, G, Natarajan, G, Nemetsky, E, Newcombe, V, Nielsen, N, Niznick, N, Noronha-Falcão, F, Nyquist, P, Olson, D, Othman, M, Owen, A, Padayachy, L, Pajoumand, M, Park, S, Pergakis, M, Perry, H, Polizzotto, L, Pouratian, N, Spivack, M, Prisco, L, Provencio, J, Puglises, F, Puybasset, L, Rao, C, Rasmussen, L, Rasulo, F, Ray, B, Ricci, Z, Richardson, R, Shinotsuka, C, Robba, C, Robertson, C, Rohaut, B, Rolston, J, Romagnoli, S, Rosanova, M, Rosenthal, E, Rowe, S, Rubin, M, Russell, M, Silva, G, Sanz, L, Sarasso, S, Sarwal, A, Schiff, N, Schnakers, C, Seder, D, Shah, V, Shapiro-Rosenbaubm, A, Shapshak, A, Sharma, K, Shutter, L, Sitt, J, Slomine, B, Smetana, K, Smielewski, P, Smith, W, Stamatakis, E, Steinberg, A, Stevens, R, Suarez, J, Sung, G, Sussman, B, Taran, S, Mazzeo, A, Thibaut, A, Thompson, D, Threlkeld, Z, Toker, D, Torbey, M, Tosto, J, Trevick, S, Tsaousi, G, Turgeon, A, Udy, A, Varelas, P, Videtta, W, Voss, H, Vox, F, Wagner, A, Wahlster, S, Wainwright, M, Whyte, J, Witherspoon, B, Yakhkind, A, Yeager, S, Young, M, Zafar, S, Zafonte, R, Zahuranec, D, Zammit, C, Zhang, B, Ziai, W, Zimmerman, L, Zink, E, Tinti, Lorenzo, Lawson, Thomas, Molteni, Erika, Kondziella, Daniel, Rass, Verena, Sharshar, Tarek, Bodien, Yelena G, Giacino, Joseph T, Mayer, Stephan A, Amiri, Moshgan, Muehlschlegel, Susanne, Venkatasubba Rao, Chethan P, Vespa, Paul M, Menon, David K, Citerio, Giuseppe, Helbok, Raimund, McNett, Molly, Agarwal, Sachin, Aiyagari, Venkatesh, Akbari, Yama, Albertson, Asher, Alexander, Sheila, Alexandrov, Anne, Alkhachroum, Ayham, Al-Mufti, Fawaz, Amiri, Moshagan, Appavu, Brian, Gebrewold, Meron Awraris, Ayounb, Marc, Badenes, Rafael, Bader, Mary Kay, Badjiata, Neeraj, Balu, Ram, Barlow, Brooke, Barra, Megan, Beekman, Rachel, Beghi, Ettore, Beqiri, Erta, Berlin, Tracey, Bilotta, Federico, Bleck, Thomas, Bodien, Yelena, Boerwinkle, Varina, Boly, Melanie, Bonnel, Alexandra, Brazzi, Luca, Brown, Emery, Bulic, Sebina, Caceres, Eder, Caceres, Adrian, Cafiero, Tullio, Carroll, Elizabeth, Cediel, Emilio G, Chou, Sherry, Claassen, Jan, Condie, Chad, Conti, Alfredo, Cosmas, Katie, Costa, Paolo, Creutzfeldt, Claire, Dangayach, Neha, Dauri, Mario, Debicki, Derek, DeGeorgia, Michael, Der-Nigoghossian, Caroline, Desai, Masoom, Dhar, Rajat, Diringer, Michael, Durr, Emily, Edlow, Brian, Ercole, Ari, Estraneo, Anna, Falcone, Guido, Farrokh, Salia, Ferguson, Adam, Fernandez-Espejo, Davinia, Fink, Ericka, Fins, Joseph, Foreman, Brandon, Franchi, Federico, Frontera, Jennifer, Ganesan, Rishi, Gaspard, Nicolas, Ghavam, Ahmeneh, Giacino, Joseph, Gibbons, Christie, Gilmore, Emily, Glustein, Chavie, Gosseries, Olivia, Green, Theresa, Greer, David, Guanci, Mary, Gupta, Deepak, Hahn, Cecil, Hakimi, Ryan, Hammond, Flora, Hanley, Daniel F, Hartings, Jed, Hassan, Ahmed, Hemphill, Claude, Da Cunha, Arthur Henrique Galvão Bruno, Hinson, Holly, Hirsch, Karen, Hocker, Sarah, Hu, Peter, Hu, Xiao, Human, Theresa, Hwang, David, Illes, Judy, Jaffa, Matthew, James, Michael L, Janas, Anna, Johnson, Susan, Jones, Morgan, Jox, Ralf J, Kalanuria, Atul, Keller, Emanuela, Kennedy, Lori, Kennelly, Megan, Keogh, Maggie, Kim, Jenn, Kim, Keri, Kirsch, Hannah, Kirschen, Matthew, Ko, Nerissa, Kreitzer, Natalie, Kromm, Julie, Kumar, Abhay, Kurtz, Pedro, Laureys, Steven, Lejeune, Nicolas, Lewis, Ariane, Liang, John, Ling, Geoffrey, Livesay, Sarah, Luppi, Andrea, MacDonald, Jennifer, Maddux, Craig, Mahanes, Dea, Mainali, Shraddha, Maldonado, Nelson, Ribeiro, Rennan Martins, Mascia, Luciana, Massimini, Marcello, Mathur, Rohan, Mayer, Stephan, McCredie, Victoria, Mejia-Mantilla, Jorge, Mendoza, Michael, Menon, David, Meyfroidt, Geert, Mijangos, Julio, Moberg, Dick, Moheet, Asma, Montalenti, Elisa, Monti, Martin, Morrison, Chris, Munar, Marina, Murtaugh, Brooke, Naccache, Lionel, Nagayama, Masao, Nairon, Emerson, Nakagawa, Thomas, Naldi, Andrea, Narenthiran, Ganesalingam, Natarajan, Girija, Nemetsky, Esther, Newcombe, Virginia, Nielsen, Niklas, Niznick, Naomi, Noronha-Falcão, Filipa, Nyquist, Paul, Olson, DaiWai, Othman, Marwan, Owen, Adrian, Padayachy, Llewellyn, Pajoumand, Mehrnaz, Park, Soojin, Pergakis, Melissa, Perry, Heidi, Polizzotto, Len, Pouratian, Nader, Spivack, Marilyn Price, Prisco, Lara, Provencio, Javier, Puglises, Francesco, Puybasset, Louis, Rao, Chethan, Rasmussen, Lindsay, Rasulo, Frank, Ray, Bappaditya, Ricci, Zaccaria, Richardson, Risa, Shinotsuka, Cassia Righy, Robba, Chiara, Robertson, Courtney, Rohaut, Benjamin, Rolston, John, Romagnoli, Stefano, Rosanova, Mario, Rosenthal, Eric, Rowe, Shaun, Rubin, Michael, Russell, Mary Beth, Silva, Gisele Sampaio, Sanz, Leandro, Sarasso, Simone, Sarwal, Aarti, Schiff, Nicolas, Schnakers, Caroline, Seder, David, Shah, Vishank Arun, Shapiro-Rosenbaubm, Amy, Shapshak, Angela, Sharma, Kartavya, Sharma, Kumar Ajay, Shutter, Lori, Sitt, Jacobo, Slomine, Beth, Smetana, Keaton, Smielewski, Peter, Smith, Wade, Stamatakis, Emmanuel, Steinberg, Alexis, Stevens, Robert, Suarez, Jose, Sung, Gene, Sussman, Bethany, Taran, Shaurya, Mazzeo, Anna Teresa, Thibaut, Aurore, Thompson, David, Threlkeld, Zachary, Toker, Daniel, Torbey, Michel, Tosto, Jenna, Trevick, Stephen, Tsaousi, Georgia, Turgeon, Alexis, Udy, Andrew, Varelas, Panos, Vespa, Paul, Videtta, Walter, Voss, Henning, Vox, Ford, Wagner, Amy, Wahlster, Sarah, Wainwright, Mark, Whyte, John, Witherspoon, Briana, Yakhkind, Aleksandra (Sasha), Yeager, Susan, Young, Michael, Zafar, Sahar, Zafonte, Ross, Zahuranec, Darin, Zammit, Chris, Zhang, Bei, Ziai, Wendy, Zimmerman, Lara, and Zink, Elizabeth

Abstract

Disorders of consciousness are neurological conditions characterized by impaired arousal and awareness of self and environment. Behavioural responses are absent or are present but fluctuate. Disorders of consciousness are commonly encountered as a consequence of both acute and chronic brain injuries, yet reliable epidemiological estimates would require inclusive, operational definitions of the concept, as well as wider knowledge dissemination among involved professionals. Whereas several manifestations have been described, including coma, vegetative state/unresponsive wakefulness syndrome and minimally conscious state, a comprehensive neurobiological definition for disorders of consciousness is still lacking. The scientific literature is primarily observational, and studies-specific aetiologies lead to disorders of consciousness. Despite advances in these disease-related forms, there remains uncertainty about whether disorders of consciousness are a disease-agnostic unitary entity with a common mechanism, prognosis or treatment response paradigm. Our knowledge of disorders of consciousness has also been hampered by heterogeneity of study designs, variables, and outcomes, leading to results that are not comparable for evidence synthesis. The different backgrounds of professionals caring for patients with disorders of consciousness and the different goals at different stages of care could partly explain this variability. The Prospective Studies working group of the Neurocritical Care Society Curing Coma Campaign was established to create a platform for observational studies and future clinical trials on disorders of consciousness and coma across the continuum of care. In this narrative review, the author panel presents limitations of prior observational clinical research and outlines practical considerations for future investigations. A narrative review format was selected to ensure that the full breadth of study design considerations could be addressed and to facilit

Published
2024

3. Common Data Elements for Disorders of Consciousness: Recommendations from the Working Group on Hospital Course, Confounders, and Medications

Author

Barra, M, Zink, E, Bleck, T, Caceres, E, Farrokh, S, Foreman, B, Cediel, E, Hemphill, J, Nagayama, M, Olson, D, Suarez, J, Aiyagari, V, Akbari, Y, Al-Mufti, F, Alexander, S, Alexandrov, A, Alkhachroum, A, Amiri, M, Appavu, B, Gebre, M, Bader, M, Badjiata, N, Balu, R, Beekman, R, Beghi, E, Bell, K, Beqiri, E, Berlin, T, Bodien, Y, Boerwinkle, V, Boly, M, Bonnel, A, Brown, E, Carroll, E, Chou, S, Citerio, G, Classen, J, Condie, C, Cosmas, K, Creutzfeldt, C, Dangayach, N, Degeorgia, M, Der-Nigoghoss, C, Desai, M, Diringer, M, Dullaway, J, Edlow, B, Ercole, A, Estraneo, A, Falcone, G, Padayachy, L, Park, S, Pergakis, M, Polizzotto, L, Pouratian, N, Spivack, M, Prisco, L, Provencio, J, Puybasset, L, Rasmussen, L, Rass, V, Richardson, R, Shinots, C, Robba, C, Robertson, C, Rohaut, B, Rolston, J, Rosanova, M, Rosenthal, E, Russell, M, Silva, G, Sanz, L, Sarasso, S, Sarwal, A, Schiff, N, Schnakers, C, Seder, D, Shah, V, Shapiro-Rosen, A, Shapshak, A, Sharma, K, Sharshar, T, Shutter, L, Sitt, J, Slomine, B, Smielewski, P, Smith, W, Stamatakis, E, Steinberg, A, Ferioli, S, Fernandez-Esp, D, Fink, E, Fins, J, Frontera, J, Ganesan, R, Ghavam, A, Giacino, J, Gibbons, C, Gilmore, E, Gosseries, O, Green, T, Greer, D, Guanci, M, Hahn, C, Hakimi, R, Hanley, D, Hartings, J, Hassan, A, Hinson, H, Hirsch, K, Hocker, S, Hu, P, Hu, X, Human, T, Hwang, D, Illes, J, Jaffa, M, James, M, Janas, A, Jones, M, Keller, E, Keogh, M, Kim, J, Kim, K, Kirsch, H, Kirschen, M, Ko, N, Kondziella, D, Kreitzer, N, Stevens, R, Sussman, B, Taran, S, Thibaut, A, Threlkeld, Z, Tinti, L, Toker, D, Torbey, M, Trevick, S, Turgeon, A, Udy, A, Varelas, P, Venkatasubba, C, Vespa, P, Videtta, W, Voss, H, Vox, F, Wagner, A, Wainwright, M, Whyte, J, Witherspoon, B, Yakhind, A, Zafonte, R, Zahuranec, D, Zammit, C, Zhang, B, Ziai, W, Zimmerman, L, Kromm, J, Kumar, A, Kurtz, P, Laureys, S, Lawson, T, Lejeune, N, Lewis, A, Liang, J, Ling, G, Livesay, S, Luppi, A, Madden, L, Maddux, C, Mahanes, D, Mainali, S, Maldonado, N, Ribeiro, R, Massimini, M, Mayer, S, Mccredie, V, Mcnett, M, Mejia-Mantill, J, Menon, D, Meyfroidt, G, Mijangos, J, Moberg, D, Moheet, A, Molteni, E, Monti, M, Morrison, C, Muehlschlegel, S, Murtaugh, B, Naccache, L, Nairon, E, Natarajan, G, Newcombe, V, Nielsen, N, Noronha-Falc‹, F, Nyquist, P, Othman, M, Owen, A, Barra M. E., Zink E. K., Bleck T. P., Caceres E., Farrokh S., Foreman B., Cediel E. G., Hemphill J. C., Nagayama M., Olson D. W. M., Suarez J. I., Aiyagari V., Akbari Y., Al-Mufti F., Alexander S., Alexandrov A., Alkhachroum A., Amiri M., Appavu B., Gebre M. A., Bader M. K., Badjiata N., Balu R., Beekman R., Beghi E., Bell K., Beqiri E., Berlin T., Bodien Y., Boerwinkle V., Boly M., Bonnel A., Brown E., Carroll E., Chou S., Citerio G., Classen J., Condie C., Cosmas K., Creutzfeldt C., Dangayach N., DeGeorgia M., Der-Nigoghoss C., Desai M., Diringer M., Dullaway J., Edlow B., Ercole A., Estraneo A., Falcone G., Padayachy L., Park S., Pergakis M., Polizzotto L., Pouratian N., Spivack M. P., Prisco L., Provencio J., Puybasset L., Rasmussen L., Rass V., Richardson R., Shinots C. R., Robba C., Robertson C., Rohaut B., Rolston J., Rosanova M., Rosenthal E., Russell M. B., Silva G. S., Sanz L., Sarasso S., Sarwal A., Schiff N., Schnakers C., Seder D., Shah V. A., Shapiro-Rosen A., Shapshak A., Sharma K., Sharshar T., Shutter L., Sitt J., Slomine B., Smielewski P., Smith W., Stamatakis E., Steinberg A., Ferioli S., Fernandez-Esp D., Fink E., Fins J., Frontera J., Ganesan R., Ghavam A., Giacino J., Gibbons C., Gilmore E., Gosseries O., Green T., Greer D., Guanci M., Hahn C., Hakimi R., Hanley D. F., Hartings J., Hassan A., Hinson H., Hirsch K., Hocker S., Hu P., Hu X., Human T., Hwang D., Illes J., Jaffa M., James M. L., Janas A., Jones M., Keller E., Keogh M., Kim J., Kim K., Kirsch H., Kirschen M., Ko N., Kondziella D., Kreitzer N., Stevens R., Sussman B., Taran S., Thibaut A., Threlkeld Z., Tinti L., Toker D., Torbey M., Trevick S., Turgeon A., Udy A., Varelas P., Venkatasubba C., Vespa P., Videtta W., Voss H., Vox F., Wagner A., Wainwright M., Whyte J., Witherspoon B., Yakhind A., Zafonte R., Zahuranec D., Zammit C., Zhang B., Ziai W., Zimmerman L., Kromm J., Kumar A., Kurtz P., Laureys S., Lawson T., Lejeune N., Lewis A., Liang J., Ling G., Livesay S., Luppi A., Madden L., Maddux C., Mahanes D., Mainali S., Maldonado N., Ribeiro R. M., Massimini M., Mayer S., McCredie V., McNett M., Mejia-Mantill J., Menon D., Meyfroidt G., Mijangos J., Moberg D., Moheet A., Molteni E., Monti M., Morrison C., Muehlschlegel S., Murtaugh B., Naccache L., Nairon E., Natarajan G., Newcombe V., Nielsen N., Noronha-Falc‹ F., Nyquist P., Othman M., Owen A., Barra, M, Zink, E, Bleck, T, Caceres, E, Farrokh, S, Foreman, B, Cediel, E, Hemphill, J, Nagayama, M, Olson, D, Suarez, J, Aiyagari, V, Akbari, Y, Al-Mufti, F, Alexander, S, Alexandrov, A, Alkhachroum, A, Amiri, M, Appavu, B, Gebre, M, Bader, M, Badjiata, N, Balu, R, Beekman, R, Beghi, E, Bell, K, Beqiri, E, Berlin, T, Bodien, Y, Boerwinkle, V, Boly, M, Bonnel, A, Brown, E, Carroll, E, Chou, S, Citerio, G, Classen, J, Condie, C, Cosmas, K, Creutzfeldt, C, Dangayach, N, Degeorgia, M, Der-Nigoghoss, C, Desai, M, Diringer, M, Dullaway, J, Edlow, B, Ercole, A, Estraneo, A, Falcone, G, Padayachy, L, Park, S, Pergakis, M, Polizzotto, L, Pouratian, N, Spivack, M, Prisco, L, Provencio, J, Puybasset, L, Rasmussen, L, Rass, V, Richardson, R, Shinots, C, Robba, C, Robertson, C, Rohaut, B, Rolston, J, Rosanova, M, Rosenthal, E, Russell, M, Silva, G, Sanz, L, Sarasso, S, Sarwal, A, Schiff, N, Schnakers, C, Seder, D, Shah, V, Shapiro-Rosen, A, Shapshak, A, Sharma, K, Sharshar, T, Shutter, L, Sitt, J, Slomine, B, Smielewski, P, Smith, W, Stamatakis, E, Steinberg, A, Ferioli, S, Fernandez-Esp, D, Fink, E, Fins, J, Frontera, J, Ganesan, R, Ghavam, A, Giacino, J, Gibbons, C, Gilmore, E, Gosseries, O, Green, T, Greer, D, Guanci, M, Hahn, C, Hakimi, R, Hanley, D, Hartings, J, Hassan, A, Hinson, H, Hirsch, K, Hocker, S, Hu, P, Hu, X, Human, T, Hwang, D, Illes, J, Jaffa, M, James, M, Janas, A, Jones, M, Keller, E, Keogh, M, Kim, J, Kim, K, Kirsch, H, Kirschen, M, Ko, N, Kondziella, D, Kreitzer, N, Stevens, R, Sussman, B, Taran, S, Thibaut, A, Threlkeld, Z, Tinti, L, Toker, D, Torbey, M, Trevick, S, Turgeon, A, Udy, A, Varelas, P, Venkatasubba, C, Vespa, P, Videtta, W, Voss, H, Vox, F, Wagner, A, Wainwright, M, Whyte, J, Witherspoon, B, Yakhind, A, Zafonte, R, Zahuranec, D, Zammit, C, Zhang, B, Ziai, W, Zimmerman, L, Kromm, J, Kumar, A, Kurtz, P, Laureys, S, Lawson, T, Lejeune, N, Lewis, A, Liang, J, Ling, G, Livesay, S, Luppi, A, Madden, L, Maddux, C, Mahanes, D, Mainali, S, Maldonado, N, Ribeiro, R, Massimini, M, Mayer, S, Mccredie, V, Mcnett, M, Mejia-Mantill, J, Menon, D, Meyfroidt, G, Mijangos, J, Moberg, D, Moheet, A, Molteni, E, Monti, M, Morrison, C, Muehlschlegel, S, Murtaugh, B, Naccache, L, Nairon, E, Natarajan, G, Newcombe, V, Nielsen, N, Noronha-Falc‹, F, Nyquist, P, Othman, M, Owen, A, Barra M. E., Zink E. K., Bleck T. P., Caceres E., Farrokh S., Foreman B., Cediel E. G., Hemphill J. C., Nagayama M., Olson D. W. M., Suarez J. I., Aiyagari V., Akbari Y., Al-Mufti F., Alexander S., Alexandrov A., Alkhachroum A., Amiri M., Appavu B., Gebre M. A., Bader M. K., Badjiata N., Balu R., Beekman R., Beghi E., Bell K., Beqiri E., Berlin T., Bodien Y., Boerwinkle V., Boly M., Bonnel A., Brown E., Carroll E., Chou S., Citerio G., Classen J., Condie C., Cosmas K., Creutzfeldt C., Dangayach N., DeGeorgia M., Der-Nigoghoss C., Desai M., Diringer M., Dullaway J., Edlow B., Ercole A., Estraneo A., Falcone G., Padayachy L., Park S., Pergakis M., Polizzotto L., Pouratian N., Spivack M. P., Prisco L., Provencio J., Puybasset L., Rasmussen L., Rass V., Richardson R., Shinots C. R., Robba C., Robertson C., Rohaut B., Rolston J., Rosanova M., Rosenthal E., Russell M. B., Silva G. S., Sanz L., Sarasso S., Sarwal A., Schiff N., Schnakers C., Seder D., Shah V. A., Shapiro-Rosen A., Shapshak A., Sharma K., Sharshar T., Shutter L., Sitt J., Slomine B., Smielewski P., Smith W., Stamatakis E., Steinberg A., Ferioli S., Fernandez-Esp D., Fink E., Fins J., Frontera J., Ganesan R., Ghavam A., Giacino J., Gibbons C., Gilmore E., Gosseries O., Green T., Greer D., Guanci M., Hahn C., Hakimi R., Hanley D. F., Hartings J., Hassan A., Hinson H., Hirsch K., Hocker S., Hu P., Hu X., Human T., Hwang D., Illes J., Jaffa M., James M. L., Janas A., Jones M., Keller E., Keogh M., Kim J., Kim K., Kirsch H., Kirschen M., Ko N., Kondziella D., Kreitzer N., Stevens R., Sussman B., Taran S., Thibaut A., Threlkeld Z., Tinti L., Toker D., Torbey M., Trevick S., Turgeon A., Udy A., Varelas P., Venkatasubba C., Vespa P., Videtta W., Voss H., Vox F., Wagner A., Wainwright M., Whyte J., Witherspoon B., Yakhind A., Zafonte R., Zahuranec D., Zammit C., Zhang B., Ziai W., Zimmerman L., Kromm J., Kumar A., Kurtz P., Laureys S., Lawson T., Lejeune N., Lewis A., Liang J., Ling G., Livesay S., Luppi A., Madden L., Maddux C., Mahanes D., Mainali S., Maldonado N., Ribeiro R. M., Massimini M., Mayer S., McCredie V., McNett M., Mejia-Mantill J., Menon D., Meyfroidt G., Mijangos J., Moberg D., Moheet A., Molteni E., Monti M., Morrison C., Muehlschlegel S., Murtaugh B., Naccache L., Nairon E., Natarajan G., Newcombe V., Nielsen N., Noronha-Falc‹ F., Nyquist P., Othman M., and Owen A.

Abstract

The convergence of an interdisciplinary team of neurocritical care specialists to organize the Curing Coma Campaign is the first effort of its kind to coordinate national and international research efforts aimed at a deeper understanding of disorders of consciousness (DoC). This process of understanding includes translational research from bench to bedside, descriptions of systems of care delivery, diagnosis, treatment, rehabilitation, and ethical frameworks. The description and measurement of varying confounding factors related to hospital care was thought to be critical in furthering meaningful research in patients with DoC. Interdisciplinary hospital care is inherently varied across geographical areas as well as community and academic medical centers. Access to monitoring technologies, specialist consultation (medical, nursing, pharmacy, respiratory, and rehabilitation), staffing resources, specialty intensive and acute care units, specialty medications and specific surgical, diagnostic and interventional procedures, and imaging is variable, and the impact on patient outcome in terms of DoC is largely unknown. The heterogeneity of causes in DoC is the source of some expected variability in care and treatment of patients, which necessitated the development of a common nomenclature and set of data elements for meaningful measurement across studies. Guideline adherence in hemorrhagic stroke and severe traumatic brain injury may also be variable due to moderate or low levels of evidence for many recommendations. This article outlines the process of the development of common data elements for hospital course, confounders, and medications to streamline definitions and variables to collect for clinical studies of DoC.

Published
2023

4. Selective Cerebrospinal Fluid Hypothermia: Bioengineering Development and In Vivo Study of an Intraventricular Cooling Device (V-COOL)

Author

Beretta, S, Versace, A, Fiore, G, Piola, M, Martini, B, Bigiogera, V, Coppadoro, L, Mariani, J, Tinti, L, Pirovano, S, Monza, L, Carone, D, Riva, M, Padovano, G, Galbiati, G, Santangelo, F, Rasponi, M, Padelli, F, Giachetti, I, Aquino, D, Diamanti, S, Librizzi, L, Bruzzone, M, De Curtis, M, Giussani, C, Sganzerla, E, Ferrarese, C, Beretta S., Versace A., Fiore G., Piola M., Martini B., Bigiogera V., Coppadoro L., Mariani J., Tinti L., Pirovano S., Monza L., Carone D., Riva M., Padovano G., Galbiati G., Santangelo F., Rasponi M., Padelli F., Giachetti I., Aquino D., Diamanti S., Librizzi L., Bruzzone M. G., De Curtis M., Giussani C., Sganzerla E. P., Ferrarese C., Beretta, S, Versace, A, Fiore, G, Piola, M, Martini, B, Bigiogera, V, Coppadoro, L, Mariani, J, Tinti, L, Pirovano, S, Monza, L, Carone, D, Riva, M, Padovano, G, Galbiati, G, Santangelo, F, Rasponi, M, Padelli, F, Giachetti, I, Aquino, D, Diamanti, S, Librizzi, L, Bruzzone, M, De Curtis, M, Giussani, C, Sganzerla, E, Ferrarese, C, Beretta S., Versace A., Fiore G., Piola M., Martini B., Bigiogera V., Coppadoro L., Mariani J., Tinti L., Pirovano S., Monza L., Carone D., Riva M., Padovano G., Galbiati G., Santangelo F., Rasponi M., Padelli F., Giachetti I., Aquino D., Diamanti S., Librizzi L., Bruzzone M. G., De Curtis M., Giussani C., Sganzerla E. P., and Ferrarese C.

Abstract

Hypothermia is a promising therapeutic strategy for severe vasospasm and other types of non-thrombotic cerebral ischemia, but its clinical application is limited by significant systemic side effects. We aimed to develop an intraventricular device for the controlled cooling of the cerebrospinal fluid, to produce a targeted hypothermia in the affected cerebral hemisphere with a minimal effect on systemic temperature. An intraventricular cooling device (acronym: V-COOL) was developed by in silico modelling, in vitro testing, and in vivo proof-of-concept application in healthy Wistar rats (n = 42). Cerebral cortical temperature, rectal temperature, and intracranial pressure were monitored at increasing flow rate (0.2 to 0.8 mL/min) and duration of application (10 to 60 min). Survival, neurological outcome, and MRI volumetric analysis of the ventricular system were assessed during the first 24 h. The V-COOL prototyping was designed to minimize extra-cranial heat transfer and intra-cranial pressure load. In vivo application of the V-COOL device produced a flow rate-dependent decrease in cerebral cortical temperature, without affecting systemic temperature. The target degree of cerebral cooling (− 3.0 °C) was obtained in 4.48 min at the flow rate of 0.4 mL/min, without significant changes in intracranial pressure. Survival and neurological outcome at 24 h showed no significant difference compared to sham-treated rats. MRI study showed a transient dilation of the ventricular system (+ 38%) in a subset of animals. The V-COOL technology provides an effective, rapid, selective, and safe cerebral cooling to a clinically relevant degree of − 3.0 °C.

Published
2022

5. Production locality and spatial diffusion of heavy flavour at high energy densities

Author

Gazdzicki, M., Kikola, D., Pidhurskyi, I., Tinti, L., Gazdzicki, M., Kikola, D., Pidhurskyi, I., and Tinti, L.

Abstract

Heavy-ion collisions are a unique tool to test the behaviour of matter in extreme conditions. The momentum correlations of charm and bottom hadrons have been considered for testing heavy quarks' thermalisation in the hot, dense medium produced by the collisions. In addition to these back-to-back correlations due to the quark-anti-quark pair creation dynamics, there are other important sources of momentum correlations, which allow us to explore the rich physics of heavy-ion collisions further. Here we show significant momentum correlations even in the thermalisation of charm quarks in the expanding medium, and this effect can be measured in collisions at sufficiently low energies. The momentum correlations depend on the correlations in the configuration space, more specifically, on the spatial separation between charm and anti-charm hadrons emission points. The pair production locality and spatial diffusion of the charm quarks give the latter. Using an example of central Pb+Pb collisions at the CERN SPS energies, we show that future measurements of the azimuthal correlations of charm and anti-charm hadrons should allow us to distinguish between different assumptions on their spatial correlations. This provides a unique window into a poorly understood sector of particle production at high-energy densities. The measurements can help to constrain the diffusion of charm quarks and verify assumptions concerning production locality of a charm and ant-charm quark pair., Comment: 12 pages main body, 17 with bibliography. 5 figures

Published
2023

6. Comorbidities in patients with epilepsy: Frequency, mechanisms and effects on long-term outcome

Author

Giussani, G, Bianchi, E, Beretta, S, Carone, D, Difrancesco, J, Stabile, A, Zanchi, C, Pirovano, M, Trentini, C, Padovano, G, Colombo, M, Cereda, D, Tinti, L, Scanziani, S, Gasparini, S, Bogliun, G, Ferrarese, C, Beghi, E, Romeo, A, Viri, M, Specchio, L, Trivisano, M, Mecarelli, O, Zarabla, A, Capovilla, G, Beccaria, F, Sasanelli, F, Galimberti, C, Tartara, E, Zamponi, N, Cappanera, S, Aguglia, U, Ferlazzo, E, La Neve, A, Luisi, C, Pontrelli, G, Cantisani, A, De Maria, G, Albanese, Y, Giussani G., Bianchi E., Beretta S., Carone D., DiFrancesco J. C., Stabile A., Zanchi C., Pirovano M., Trentini C., Padovano G., Colombo M., Cereda D., Tinti L., Scanziani S., Gasparini S., Bogliun G., Ferrarese C., Beghi E., Romeo A., Viri M., Specchio L., Trivisano M., Mecarelli O., Zarabla A., Capovilla G., Beccaria F., Sasanelli F., Galimberti C. A., Tartara E., Zamponi N., Cappanera S., Aguglia U., Ferlazzo E., La Neve A., Luisi C., Pontrelli G., Cantisani A. T., De Maria G., Albanese Y., Giussani, G, Bianchi, E, Beretta, S, Carone, D, Difrancesco, J, Stabile, A, Zanchi, C, Pirovano, M, Trentini, C, Padovano, G, Colombo, M, Cereda, D, Tinti, L, Scanziani, S, Gasparini, S, Bogliun, G, Ferrarese, C, Beghi, E, Romeo, A, Viri, M, Specchio, L, Trivisano, M, Mecarelli, O, Zarabla, A, Capovilla, G, Beccaria, F, Sasanelli, F, Galimberti, C, Tartara, E, Zamponi, N, Cappanera, S, Aguglia, U, Ferlazzo, E, La Neve, A, Luisi, C, Pontrelli, G, Cantisani, A, De Maria, G, Albanese, Y, Giussani G., Bianchi E., Beretta S., Carone D., DiFrancesco J. C., Stabile A., Zanchi C., Pirovano M., Trentini C., Padovano G., Colombo M., Cereda D., Tinti L., Scanziani S., Gasparini S., Bogliun G., Ferrarese C., Beghi E., Romeo A., Viri M., Specchio L., Trivisano M., Mecarelli O., Zarabla A., Capovilla G., Beccaria F., Sasanelli F., Galimberti C. A., Tartara E., Zamponi N., Cappanera S., Aguglia U., Ferlazzo E., La Neve A., Luisi C., Pontrelli G., Cantisani A. T., De Maria G., and Albanese Y.

Abstract

Objective: To assess frequency, types, and mechanisms of comorbidities in people with epilepsy and verify their association with disease features and outcome. Methods: This cohort study was performed in 13 Italian epilepsy centers with nationwide distribution and accurate records. Eligible patients were children and adults diagnosed before December 31, 2005, and followed for a minimum of 10 years. Two pairs of raters independently reviewed patients’ records and classified each comorbidity. In case of disagreement, a third reviewer made the final decision. Comorbidities were classified according to type (organ/system) and underlying mechanism (causal, shared risk factors, chance association). Comorbidity types and mechanisms were described in the entire sample and according to epilepsy prognostic patterns (sustained remission, relapsing-remitting course, no remission). Results: Of 1006 included patients, 266 (26.4%) had at least one comorbidity. The most common were developmental/perinatal (7.5% of cases), psychiatric (6.2%), cardiovascular (5.3%), and endocrine/metabolic (3.8%). Among 408 reported comorbidities, the underlying mechanisms were, in decreasing order, chance association (42.2%), shared risk factors (31.1%), and causal (26.7%). Psychiatric diseases were present in 13.3% of patients with no remission, 5.9% of patients with relapsing-remitting course, and 4.8% of patients with sustained remission (p =.016). The corresponding numbers for endocrine/metabolic diseases were respectively, 9.6%, 3.4%, and 2.9% (p =.013); for respiratory diseases were 3.6%,.3%, and.3% (p =.001), and for urogenital diseases were 3.6%,.7%, and 1.6% (p =.048). The association of endocrine/metabolic, psychiatric, and respiratory comorbidities with epilepsy prognosis was confirmed by multivariable analysis adjusted for the main demographic and clinical variables, with patients with these comorbidities showing a lower probability of achieving remission. Signifi

Published
2021

7. Discontinuation of antiseizure medications in seizure-free patients with long-term follow-up: Patients’ profile, seizure recurrence, and risk factors

Author

Beghi, E, Beretta, S, Colombo, M, Bianchi, E, Carone, D, Zanchi, C, Tinti, L, Pirovano, M, Trentini, C, Padovano, G, Cereda, D, Scanziani, S, Giussani, G, Gasparini, S, Bogliun, G, Ferrarese, C, Beghi E., Beretta S., Colombo M., Bianchi E., Carone D., Zanchi C., Tinti L., Pirovano M., Trentini C., Padovano G., Cereda D., Scanziani S., Giussani G., Gasparini S., Bogliun G., Ferrarese C., Beghi, E, Beretta, S, Colombo, M, Bianchi, E, Carone, D, Zanchi, C, Tinti, L, Pirovano, M, Trentini, C, Padovano, G, Cereda, D, Scanziani, S, Giussani, G, Gasparini, S, Bogliun, G, Ferrarese, C, Beghi E., Beretta S., Colombo M., Bianchi E., Carone D., Zanchi C., Tinti L., Pirovano M., Trentini C., Padovano G., Cereda D., Scanziani S., Giussani G., Gasparini S., Bogliun G., and Ferrarese C.

Abstract

Objective: To compare withdrawal of antiseizure medications (ASM) to continued treatment in newly diagnosed individuals achieving seizure freedom, and assess the risk of relapse and factors associated with relapse. Methods: This is a multicenter retrospective cohort study with long-term follow-up. Patients with newly diagnosed epilepsy were identified from the medical records of 13 Italian epilepsy centers and followed up until the most recent visit or death. Seizure-free patients discontinuing treatment were compared to patients who maintained treatment for baseline characteristics. Treatment was stopped upon clinical judgment. The probability of relapse was calculated with the Kaplan–Meier method. Demographic, clinical, and instrumental variables associated with relapse were assessed with Cox proportional hazards models. Results: One thousand and six patients aged 1 month to 72 years at diagnosis were enrolled and followed up for 17,892 person-years (median follow-up, 9.9 years). Three hundred and twenty patients (31.8%) underwent one or more treatment discontinuations. Factors associated with ASM withdrawal were younger age at remission and normal psychiatric examination. The probability of relapse after the first withdrawal was 16% at six months, 24% at 12 months, and 36%, 45%, and 53% at three, five, and ten years, respectively. The probability of remission after the first relapse was 59% at one month, 67%, 72, and 76% at three, six, and 12 months, respectively. Variables associated with relapse were age 14+ years, structural etiology, abnormal neuroimaging, ASM initiation after a single seizure, and symptomatic/cryptogenic epilepsy. Conclusions: About one half of seizure-free patients stopping ASM relapse in 10 years. However, the possibility of remission after relapse is high, particularly in children and patients with idiopathic/cryptogenic epilepsy. Treatment deprescription might be encouraged at least in these patients.

Published
2021

8. Long-term risk of chronic epilepsy in adults after post-anoxic coma and refractory status epilepticus: A retrospective cohort study

Author

Tinti, L, Beretta, S, Coppo, A, Bianchi, E, Zanchi, C, Carone, D, Stabile, A, Padovano, G, Sulmina, E, Greco, G, Diamanti, S, Difrancesco, J, Bogliun, G, Foti, G, Ferrarese, C, Beghi, E, Avalli, L, Tinti L., Beretta S., Coppo A., Bianchi E., Zanchi C., Carone D., Stabile A., Padovano G., Sulmina E., Greco G., Diamanti S., Difrancesco J. C., Bogliun G., Foti G., Ferrarese C., Beghi E., Avalli L., Tinti, L, Beretta, S, Coppo, A, Bianchi, E, Zanchi, C, Carone, D, Stabile, A, Padovano, G, Sulmina, E, Greco, G, Diamanti, S, Difrancesco, J, Bogliun, G, Foti, G, Ferrarese, C, Beghi, E, Avalli, L, Tinti L., Beretta S., Coppo A., Bianchi E., Zanchi C., Carone D., Stabile A., Padovano G., Sulmina E., Greco G., Diamanti S., Difrancesco J. C., Bogliun G., Foti G., Ferrarese C., Beghi E., and Avalli L.

Published
2021

9. Incidence and prevalence of coma in the UK and the USA

Author

Kondziella, D, Amiri, M, Othman, M, Beghi, E, Bodien, Y, Citerio, G, Giacino, J, Mayer, S, Lawson, T, Menon, D, Rass, V, Sharshar, T, Stevens, R, Tinti, L, Vespa, P, Mcnett, M, Venkatasubba Rao, C, Helbok, R, Akbari, Y, Boly, M, Dangayach, N, Edlow, B, Foreman, B, Gilmore, E, Hammond, F, Hemphill, J, Human, T, Madden, L, Mainali, S, Meyfroidt, G, Monti, M, Nakase-Richardson, R, Nyquist, P, Olson, D, Park, S, Provencio, J, Puybasset, L, Sarwal, A, Shutter, L, Witherspoon, B, Whyte, J, Ziai, W, Kondziella, Daniel, Amiri, Moshgan, Othman, Marwan H, Beghi, Ettore, Bodien, Yelena G, Citerio, Giuseppe, Giacino, Joseph T, Mayer, Stephan A, Lawson, Thomas N, Menon, David K, Rass, Verena, Sharshar, Tarek, Stevens, Robert D, Tinti, Lorenzo, Vespa, Paul, McNett, Molly, Venkatasubba Rao, Chethan P, Helbok, Raimund, Akbari, Yama, Boly, Melanie, Dangayach, Neha, Edlow, Brian, Foreman, Brandon, Gilmore, Emily, Hammond, Flora M, Hemphill, J Claude, Human, Theresa, Madden, Lori Kennedy, Mainali, Shraddha, Meyfroidt, Geert, Monti, Martin, Nakase-Richardson, Risa, Nyquist, Paul, Olson, DaiWai, Park, Soojin, Provencio, Jose Javier, Puybasset, Louis, Sarwal, Aarti, Shutter, Lori, Witherspoon, Briana, Whyte, John, Ziai, Wendy, Kondziella, D, Amiri, M, Othman, M, Beghi, E, Bodien, Y, Citerio, G, Giacino, J, Mayer, S, Lawson, T, Menon, D, Rass, V, Sharshar, T, Stevens, R, Tinti, L, Vespa, P, Mcnett, M, Venkatasubba Rao, C, Helbok, R, Akbari, Y, Boly, M, Dangayach, N, Edlow, B, Foreman, B, Gilmore, E, Hammond, F, Hemphill, J, Human, T, Madden, L, Mainali, S, Meyfroidt, G, Monti, M, Nakase-Richardson, R, Nyquist, P, Olson, D, Park, S, Provencio, J, Puybasset, L, Sarwal, A, Shutter, L, Witherspoon, B, Whyte, J, Ziai, W, Kondziella, Daniel, Amiri, Moshgan, Othman, Marwan H, Beghi, Ettore, Bodien, Yelena G, Citerio, Giuseppe, Giacino, Joseph T, Mayer, Stephan A, Lawson, Thomas N, Menon, David K, Rass, Verena, Sharshar, Tarek, Stevens, Robert D, Tinti, Lorenzo, Vespa, Paul, McNett, Molly, Venkatasubba Rao, Chethan P, Helbok, Raimund, Akbari, Yama, Boly, Melanie, Dangayach, Neha, Edlow, Brian, Foreman, Brandon, Gilmore, Emily, Hammond, Flora M, Hemphill, J Claude, Human, Theresa, Madden, Lori Kennedy, Mainali, Shraddha, Meyfroidt, Geert, Monti, Martin, Nakase-Richardson, Risa, Nyquist, Paul, Olson, DaiWai, Park, Soojin, Provencio, Jose Javier, Puybasset, Louis, Sarwal, Aarti, Shutter, Lori, Witherspoon, Briana, Whyte, John, and Ziai, Wendy

Abstract

The epidemiology of coma is unknown because case ascertainment with traditional methods is difficult. Here, we used crowdsourcing methodology to estimate the incidence and prevalence of coma in the UK and the USA. We recruited UK and US laypeople (aged ≥18 years) who were nationally representative (i.e. matched for age, gender and ethnicity according to census data) of the UK and the USA, respectively, utilizing a crowdsourcing platform. We provided a description of coma and asked survey participants if they—‘right now’ or ‘within the last year’—had a family member in coma. These participants (UK n = 994, USA n = 977) provided data on 30 387 family members (UK n = 14 124, USA n = 16 263). We found more coma cases in the USA (n = 47) than in the UK (n = 20; P = 0.009). We identified one coma case in the UK (0.007%, 95% confidence interval 0.00–0.04%) on the day of the survey and 19 new coma cases (0.13%, 95% confidence interval 0.08–0.21%) within the preceding year, resulting in an annual incidence of 135/100 000 (95% confidence interval 81–210) and a point prevalence of 7 cases per 100 000 population (95% confidence interval 0.18–39.44) in the UK. We identified five cases in the USA (0.031%, 95% confidence interval 0.01–0.07%) on the day of the survey and 42 new cases (0.26%, 95% confidence interval 0.19–0.35%) within the preceding year, resulting in an annual incidence of 258/100 000 (95% confidence interval 186–349) and a point prevalence of 31 cases per 100 000 population (95% confidence interval 9.98–71.73) in the USA. The five most common causes were stroke, medically induced coma, COVID-19, traumatic brain injury and cardiac arrest. To summarize, for the first time, we report incidence and prevalence estimates for coma across diagnosis types and settings in the UK and the USA using crowdsourcing methods. Coma may be more prevalent in the USA than in the UK, which requires further investigation. These data are urgently needed to expand the public health perspec

Published
2022

10. Incidence and prevalence of coma in the UK and the USA

Author

Kondziella, D, Amiri, M, Othman, M, Beghi, E, Bodien, Y, Citerio, G, Giacino, J, Mayer, S, Lawson, T, Menon, D, Rass, V, Sharshar, T, Stevens, R, Tinti, L, Vespa, P, Mcnett, M, Venkatasubba Rao, C, Helbok, R, Akbari, Y, Boly, M, Dangayach, N, Edlow, B, Foreman, B, Gilmore, E, Hammond, F, Hemphill, J, Human, T, Madden, L, Mainali, S, Meyfroidt, G, Monti, M, Nakase-Richardson, R, Nyquist, P, Olson, D, Park, S, Provencio, J, Puybasset, L, Sarwal, A, Shutter, L, Witherspoon, B, Whyte, J, Ziai, W, Kondziella, Daniel, Amiri, Moshgan, Othman, Marwan H, Beghi, Ettore, Bodien, Yelena G, Citerio, Giuseppe, Giacino, Joseph T, Mayer, Stephan A, Lawson, Thomas N, Menon, David K, Rass, Verena, Sharshar, Tarek, Stevens, Robert D, Tinti, Lorenzo, Vespa, Paul, McNett, Molly, Venkatasubba Rao, Chethan P, Helbok, Raimund, Akbari, Yama, Boly, Melanie, Dangayach, Neha, Edlow, Brian, Foreman, Brandon, Gilmore, Emily, Hammond, Flora M, Hemphill, J Claude, Human, Theresa, Madden, Lori Kennedy, Mainali, Shraddha, Meyfroidt, Geert, Monti, Martin, Nakase-Richardson, Risa, Nyquist, Paul, Olson, DaiWai, Park, Soojin, Provencio, Jose Javier, Puybasset, Louis, Sarwal, Aarti, Shutter, Lori, Witherspoon, Briana, Whyte, John, Ziai, Wendy, Kondziella, D, Amiri, M, Othman, M, Beghi, E, Bodien, Y, Citerio, G, Giacino, J, Mayer, S, Lawson, T, Menon, D, Rass, V, Sharshar, T, Stevens, R, Tinti, L, Vespa, P, Mcnett, M, Venkatasubba Rao, C, Helbok, R, Akbari, Y, Boly, M, Dangayach, N, Edlow, B, Foreman, B, Gilmore, E, Hammond, F, Hemphill, J, Human, T, Madden, L, Mainali, S, Meyfroidt, G, Monti, M, Nakase-Richardson, R, Nyquist, P, Olson, D, Park, S, Provencio, J, Puybasset, L, Sarwal, A, Shutter, L, Witherspoon, B, Whyte, J, Ziai, W, Kondziella, Daniel, Amiri, Moshgan, Othman, Marwan H, Beghi, Ettore, Bodien, Yelena G, Citerio, Giuseppe, Giacino, Joseph T, Mayer, Stephan A, Lawson, Thomas N, Menon, David K, Rass, Verena, Sharshar, Tarek, Stevens, Robert D, Tinti, Lorenzo, Vespa, Paul, McNett, Molly, Venkatasubba Rao, Chethan P, Helbok, Raimund, Akbari, Yama, Boly, Melanie, Dangayach, Neha, Edlow, Brian, Foreman, Brandon, Gilmore, Emily, Hammond, Flora M, Hemphill, J Claude, Human, Theresa, Madden, Lori Kennedy, Mainali, Shraddha, Meyfroidt, Geert, Monti, Martin, Nakase-Richardson, Risa, Nyquist, Paul, Olson, DaiWai, Park, Soojin, Provencio, Jose Javier, Puybasset, Louis, Sarwal, Aarti, Shutter, Lori, Witherspoon, Briana, Whyte, John, and Ziai, Wendy

Abstract

The epidemiology of coma is unknown because case ascertainment with traditional methods is difficult. Here, we used crowdsourcing methodology to estimate the incidence and prevalence of coma in the UK and the USA. We recruited UK and US laypeople (aged ≥18 years) who were nationally representative (i.e. matched for age, gender and ethnicity according to census data) of the UK and the USA, respectively, utilizing a crowdsourcing platform. We provided a description of coma and asked survey participants if they - 'right now' or 'within the last year' - had a family member in coma. These participants (UK n = 994, USA n = 977) provided data on 30 387 family members (UK n = 14 124, USA n = 16 263). We found more coma cases in the USA (n = 47) than in the UK (n = 20; P = 0.009). We identified one coma case in the UK (0.007%, 95% confidence interval 0.00-0.04%) on the day of the survey and 19 new coma cases (0.13%, 95% confidence interval 0.08-0.21%) within the preceding year, resulting in an annual incidence of 135/100 000 (95% confidence interval 81-210) and a point prevalence of 7 cases per 100 000 population (95% confidence interval 0.18-39.44) in the UK. We identified five cases in the USA (0.031%, 95% confidence interval 0.01-0.07%) on the day of the survey and 42 new cases (0.26%, 95% confidence interval 0.19-0.35%) within the preceding year, resulting in an annual incidence of 258/100 000 (95% confidence interval 186-349) and a point prevalence of 31 cases per 100 000 population (95% confidence interval 9.98-71.73) in the USA. The five most common causes were stroke, medically induced coma, COVID-19, traumatic brain injury and cardiac arrest. To summarize, for the first time, we report incidence and prevalence estimates for coma across diagnosis types and settings in the UK and the USA using crowdsourcing methods. Coma may be more prevalent in the USA than in the UK, which requires further investigation. These data are urgently needed to expand the public health per

Published
2022

11. Relativistic quantum fluid with boost invariance

Author

Rindori, D., Tinti, L., Becattini, F., Rischke, D., Rindori, D., Tinti, L., Becattini, F., and Rischke, D.

Abstract

We study a relativistic fluid with longitudinal boost invariance in a quantum-statistical framework as an example of a solvable non-equilibrium problem. For the free quantum field, we calculate the exact form of the expectation values of the stress-energy tensor and the entropy current. For the stress-energy tensor, we find that a finite value can be obtained only by subtracting the vacuum of the density operator at some fixed proper time \tau_0. As a consequence, the stress-energy tensor acquires non-trivial quantum corrections to the classical free-streaming form., Comment: 19 pages, 1 figure

Published
2021
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12. Spectral properties of the EEG during recovery of consciousness after acute brain injury

Author

Napolitani, M, Colombo, M, Curto, F, Tinti, L, Beretta, S, Citerio, G, Rosanova, M, Sarasso, S, Chieregato, A, M. Napolitani, M. Colombo, F. Curto, L. Tinti, S. Beretta, G. Citerio, M. Rosanova, S. Sarasso, A. Chieregato, Napolitani, M, Colombo, M, Curto, F, Tinti, L, Beretta, S, Citerio, G, Rosanova, M, Sarasso, S, Chieregato, A, M. Napolitani, M. Colombo, F. Curto, L. Tinti, S. Beretta, G. Citerio, M. Rosanova, S. Sarasso, and A. Chieregato

Published
2020

13. Spectral properties of the EEG during recovery of consciousness after acute brain injury

Author

Napolitani, M, Colombo, M, Curto, F, Tinti, L, Beretta, S, Citerio, G, Rosanova, M, Sarasso, S, Chieregato, A, M. Napolitani, M. Colombo, F. Curto, L. Tinti, S. Beretta, G. Citerio, M. Rosanova, S. Sarasso, A. Chieregato, Napolitani, M, Colombo, M, Curto, F, Tinti, L, Beretta, S, Citerio, G, Rosanova, M, Sarasso, S, Chieregato, A, M. Napolitani, M. Colombo, F. Curto, L. Tinti, S. Beretta, G. Citerio, M. Rosanova, S. Sarasso, and A. Chieregato

Published
2020

14. Resummed hydrodynamic expansion for a plasma of particles interacting with fields

Author

Tinti, L., Vujanovic, G., Noronha, J., Heinz, U., Tinti, L., Vujanovic, G., Noronha, J., and Heinz, U.

Abstract

A novel description of kinetic theory dynamics is proposed in terms of resummed moments that embed information of both hydrodynamic and non-hydrodynamic modes. The resulting expansion can be used to extend hydrodynamics to higher orders in a consistent and numerically efficient way; at lowest order it reduces to an Israel-Stewart-like theory. This formalism is especially suited to investigate the general problem of particles interacting with fields. We tested the accuracy of this approach against the exact solution of the coupled Boltzmann-Vlasov-Maxwell equations for a plasma in an electromagnetic field undergoing Bjorken-like expansion, including extreme cases characterized by large deviations from local equilibrium and large electric fields. We show that this new resummed method maintains the fast convergence of the traditional method of moments. We also find a new condition, unrelated to Knudsen numbers and pressure corrections, that justifies the truncation of the series even in situations far from local thermal equilibrium.

Published
2018
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15. Resummed hydrodynamic expansion for a plasma of particles interacting with fields

Author

Tinti, L., Vujanovic, G., Noronha, J., Heinz, U., Tinti, L., Vujanovic, G., Noronha, J., and Heinz, U.

Abstract

A novel description of kinetic theory dynamics is proposed in terms of resummed moments that embed information of both hydrodynamic and non-hydrodynamic modes. The resulting expansion can be used to extend hydrodynamics to higher orders in a consistent and numerically efficient way; at lowest order it reduces to an Israel-Stewart-like theory. This formalism is especially suited to investigate the general problem of particles interacting with fields. We tested the accuracy of this approach against the exact solution of the coupled Boltzmann-Vlasov-Maxwell equations for a plasma in an electromagnetic field undergoing Bjorken-like expansion, including extreme cases characterized by large deviations from local equilibrium and large electric fields. We show that this new resummed method maintains the fast convergence of the traditional method of moments. We also find a new condition, unrelated to Knudsen numbers and pressure corrections, that justifies the truncation of the series even in situations far from local thermal equilibrium.

Published
2018
Full Text
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16. Local thermodynamical equilibrium and the beta frame for a quantum relativistic fluid

Author

Becattini, F., Bucciantini, L., Grossi, E., Tinti, L., Becattini, F., Bucciantini, L., Grossi, E., and Tinti, L.

Abstract

We discuss the concept of local thermodynamical equilibrium in relativistic hydrodynamics in flat spacetime in a quantum statistical framework without an underlying kinetic description, suitable for strongly interacting fluids. We show that the appropriate definition of local equilibrium naturally leads to the introduction of a relativistic hydrodynamical frame in which the four-velocity vector is the one of a relativistic thermometer at equilibrium with the fluid, parallel to the inverse temperature four-vector \beta, which then becomes a primary quantity. We show that this frame is the most appropriate for the expansion of stress-energy tensor from local thermodynamical equilibrium and that therein the local laws of thermodynamics take on their simplest form. We discuss the difference between the \beta frame and Landau frame and present an instance where they differ., Comment: 22 pages, 3 figures. To appear in Eur. Phys. J. C

Published
2014
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17. Local thermodynamical equilibrium and the beta frame for a quantum relativistic fluid

Author

Becattini, F., Bucciantini, L., Grossi, E., Tinti, L., Becattini, F., Bucciantini, L., Grossi, E., and Tinti, L.

Abstract

We discuss the concept of local thermodynamical equilibrium in relativistic hydrodynamics in flat spacetime in a quantum statistical framework without an underlying kinetic description, suitable for strongly interacting fluids. We show that the appropriate definition of local equilibrium naturally leads to the introduction of a relativistic hydrodynamical frame in which the four-velocity vector is the one of a relativistic thermometer at equilibrium with the fluid, parallel to the inverse temperature four-vector \beta, which then becomes a primary quantity. We show that this frame is the most appropriate for the expansion of stress-energy tensor from local thermodynamical equilibrium and that therein the local laws of thermodynamics take on their simplest form. We discuss the difference between the \beta frame and Landau frame and present an instance where they differ., Comment: 22 pages, 3 figures. To appear in Eur. Phys. J. C

Published
2014
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18. Nonequilibrium Thermodynamical Inequivalence of Quantum Stress-energy and Spin Tensors

Author

Becattini, F., Tinti, L., Becattini, F., and Tinti, L.

Abstract

It is shown that different pairs of stress-energy and spin tensors of quantum relativistic fields related by a pseudo-gauge transformation, i.e. differing by a divergence, imply different mean values of physical quantities in thermodynamical nonequilibrium situations. Most notably, transport coefficients and the total entropy production rate are affected by the choice of the spin tensor of the relativistic quantum field theory under consideration. Therefore, at least in principle, it should be possible to disprove a fundamental stress-energy tensor and/or to show that a fundamental spin tensor exists by means of a dissipative thermodynamical experiment., Comment: 18 pages. Final version accepted for publication in Phys Rev D

Published
2012
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19. Nonequilibrium Thermodynamical Inequivalence of Quantum Stress-energy and Spin Tensors

Author

Becattini, F., Tinti, L., Becattini, F., and Tinti, L.

Abstract

It is shown that different pairs of stress-energy and spin tensors of quantum relativistic fields related by a pseudo-gauge transformation, i.e. differing by a divergence, imply different mean values of physical quantities in thermodynamical nonequilibrium situations. Most notably, transport coefficients and the total entropy production rate are affected by the choice of the spin tensor of the relativistic quantum field theory under consideration. Therefore, at least in principle, it should be possible to disprove a fundamental stress-energy tensor and/or to show that a fundamental spin tensor exists by means of a dissipative thermodynamical experiment., Comment: 18 pages. Final version accepted for publication in Phys Rev D

Published
2012
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20. Thermodynamical inequivalence of quantum stress-energy and spin tensors

Author

Becattini, F., Tinti, L., Becattini, F., and Tinti, L.

Abstract

It is shown that different couples of stress-energy and spin tensors of quantum relativistic fields, which would be otherwise equivalent, are in fact inequivalent if the second law of thermodynamics is taken into account. The proof of the inequivalence is based on the analysis of a macroscopic system at full thermodynamical equilibrium with a macroscopic total angular momentum and a specific instance is given for the free Dirac field, for which we show that the canonical and Belinfante stress-energy tensors are not equivalent. For this particular case, we show that the difference between the predicted angular momentum densities for a rotating system at full thermodynamical equilibrium is a quantum effect, persisting in the non-relativistic limit, corresponding to a polarization of particles of the order of \hbar \omega/KT (\omega being the angular velocity) and could in principle be measured experimentally. This result implies that specific stress-energy and spin tensors are physically meaningful even in the absence of gravitational coupling and raises the issue of finding the thermodynamically right (or the right class of) tensors. We argue that the maximization of the thermodynamic potential theoretically allows to discriminate between two different couples, yet for the present we are unable to provide a theoretical method to single out the "best" couple of tensors in a given quantum field theory. The existence of a non-vanishing spin tensor would have major consequences in hydrodynamics, gravity and cosmology., Comment: 25 pages, 3 figures. Final version accepted for publication in Phys. Rev. D

Published
2011
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21. Thermodynamical inequivalence of quantum stress-energy and spin tensors

Author

Becattini, F., Tinti, L., Becattini, F., and Tinti, L.

Abstract

It is shown that different couples of stress-energy and spin tensors of quantum relativistic fields, which would be otherwise equivalent, are in fact inequivalent if the second law of thermodynamics is taken into account. The proof of the inequivalence is based on the analysis of a macroscopic system at full thermodynamical equilibrium with a macroscopic total angular momentum and a specific instance is given for the free Dirac field, for which we show that the canonical and Belinfante stress-energy tensors are not equivalent. For this particular case, we show that the difference between the predicted angular momentum densities for a rotating system at full thermodynamical equilibrium is a quantum effect, persisting in the non-relativistic limit, corresponding to a polarization of particles of the order of \hbar \omega/KT (\omega being the angular velocity) and could in principle be measured experimentally. This result implies that specific stress-energy and spin tensors are physically meaningful even in the absence of gravitational coupling and raises the issue of finding the thermodynamically right (or the right class of) tensors. We argue that the maximization of the thermodynamic potential theoretically allows to discriminate between two different couples, yet for the present we are unable to provide a theoretical method to single out the "best" couple of tensors in a given quantum field theory. The existence of a non-vanishing spin tensor would have major consequences in hydrodynamics, gravity and cosmology., Comment: 25 pages, 3 figures. Final version accepted for publication in Phys. Rev. D

Published
2011
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22. The ideal relativistic rotating gas as a perfect fluid with spin

Author

Becattini, F., Tinti, L., Becattini, F., and Tinti, L.

Abstract

We show that the ideal relativistic spinning gas at complete thermodynamical equilibrium is a fluid with a non-vanishing spin density tensor \sigma_\mu \nu. After having obtained the expression of the local spin-dependent phase space density f(x,p)_(\sigma \tau) in the Boltzmann approximation, we derive the spin density tensor and show that it is proportional to the acceleration tensor Omega_\mu \nu constructed with the Frenet-Serret tetrad. We recover the proper generalization of the fundamental thermodynamical relation, involving an additional term -(1/2) \Omega_\mu \nu \sigma^\mu \nu. We also show that the spin density tensor has a non-vanishing projection onto the four-velocity field, i.e. t^\mu= sigma_\mu \nu u^\nu \ne 0, in contrast to the common assumption t^\mu = 0, known as Frenkel condition, in the thus-far proposed theories of relativistic fluids with spin. We briefly address the viewpoint of the accelerated observer and inertial spin effects., Comment: Final published version in Annals of Physics

Published
2009
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23. The ideal relativistic rotating gas as a perfect fluid with spin

Author

Becattini, F., Tinti, L., Becattini, F., and Tinti, L.

Abstract

We show that the ideal relativistic spinning gas at complete thermodynamical equilibrium is a fluid with a non-vanishing spin density tensor \sigma_\mu \nu. After having obtained the expression of the local spin-dependent phase space density f(x,p)_(\sigma \tau) in the Boltzmann approximation, we derive the spin density tensor and show that it is proportional to the acceleration tensor Omega_\mu \nu constructed with the Frenet-Serret tetrad. We recover the proper generalization of the fundamental thermodynamical relation, involving an additional term -(1/2) \Omega_\mu \nu \sigma^\mu \nu. We also show that the spin density tensor has a non-vanishing projection onto the four-velocity field, i.e. t^\mu= sigma_\mu \nu u^\nu \ne 0, in contrast to the common assumption t^\mu = 0, known as Frenkel condition, in the thus-far proposed theories of relativistic fluids with spin. We briefly address the viewpoint of the accelerated observer and inertial spin effects., Comment: Final published version in Annals of Physics

Published
2009
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