73 results on '"Tocci M"'
Search Results
2. Development of a model for the prediction of mechanical properties for Al-Si-Mg castings
- Author
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Ransenigo, C., Tocci, M., Viscardi, C., Serafini, M., and Pola, A.
- Subjects
MODEL ,ALUMINUM ,CASTING ,HEAT TREATMENT ,SIMULATION - Published
- 2022
3. Mechanical spectroscopy study of as-cast and additive manufactured AlSi10Mg
- Author
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Cabibbo, M, Montanari, R, Pola, A, Tocci, M, and Varone, A
- Subjects
Settore ING-IND/21 ,Mechanical spectroscopy ,Mechanics of Materials ,Additive manufacturing ,XRD ,Mechanical Engineering ,Materials Chemistry ,Metals and Alloys ,AlSi10Mg ,Casting ,Electron microscopy ,Microstructure - Published
- 2022
4. Numerical simulation of laser powder bed fusion processes
- Author
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Abrami, M, Ransenigo, C, Tocci, M, Pola, A, Obeidi, M, and Brabazon, D
- Subjects
LASER POWDER BED FUSION (L-PBF) ,NUMERICAL SIMULATION ,ADDITIVE MANUFACTURING ,STAINLESS STEEL - Published
- 2021
5. Characterization of microstructural and mechanical properties of high-pressure die-cast en ac 46000 alloy
- Author
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Tocci, M, Ferri, S, Montesano, L, and Pola, A
- Subjects
INTERMETALLICS ,HIGH PRESSURE DIE CASTING ,MICROSTRUCTURE ,TENSILE PROPERTIES - Published
- 2021
6. Development and validation of a risk score for chronic kidney disease in HIV infection using prospective cohort data from the D:A:D study
- Author
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Mocroft, Amanda, Lundgren, Jens D., Ross, Michael, Law, Matthew, Reiss, Peter, Kirk, Ole, Smith, Colette, Wentworth, Deborah, Neuhaus, Jacqueline, Fux, Christoph A., Moranne, Olivier, Morlat, Phillipe, Johnson, Margaret A., Ryom, Lene, Lundgren, J. D., Powderly, B., Shortman, N., Moecklinghoff, C., Reilly, G., Franquet, X., Sabin, C. A., Phillips, A., Kirk, O., Reiss, P., Weber, R., Pradier, C., Law, M., d'Arminio Monforte, A., Dabis, F., El-Sadr, W. M., De Wit, S., Ryom, L., Kamara, D., Smith, C., Mocroft, A., Tverland, J., Mansfeld, M., Nielsen, J., Raben, D., Salbøl Brandt, R., Rickenbach, M., Fanti, I., Krum, E., Hillebregt, M., Geffard, S., Sundström, A., Delforge, M., Fontas, E., Torres, F., Mcmanus, H., Wright, S., Kjær, J., Sjøl, A., Meidahl, P., Helweg-Larsen, J., Schmidt Iversen, J., Ross, M., Fux, C. A., Morlat, P., Moranne, O., Kesselring, A. M., Kamara, D. A., Friis-Møller, N., Kowalska, J., Sabin, C., Bruyand, M., Bower, M., Fätkenheuer, G., Donald, A., Grulich, A., Prins, J. M., Kuijpers, T. W., Scherpbier, H. J., van der Meer, J. T. M., Wit, F. W. M. N., Godfried, M. H., van der Poll, T., Nellen, F. J. B., Geerlings, S. E., van Vugt, M., Pajkrt, D., Bos, J. C., Wiersinga, W. J., van der Valk, M., Goorhuis, A., Hovius, J. W., van Eden, J., Henderiks, A., van Hes, A. M. H., Mutschelknauss, M., Nobel, H. E., Pijnappel, F. J. J., Westerman, A. M., Jurriaans, S., Back, N. K. T., Zaaijer, H. L., Berkhout, B., Cornelissen, M. T. E., Schinkel, C. J., Thomas, X. V., van den Berge, M., Stegeman, A., Baas, S., Hage de Looff, L., Versteeg, D., Pronk, M. J. H., Ammerlaan, H. S. M., Korsten-Vorstermans, E. M. H. M., de Munnik, E. S., Jansz, A. R., Tjhie, J., Wegdam, M. C. A., Deiman, B., Scharnhorst, V., van der Plas, A., Weijsenfeld, A. M., van der Ende, M. E., de Vries-Sluijs, T. E. M. S., C. M. van Gorp, E., Schurink, C. A. M., Nouwen, J. L., Verbon, A., Rijnders, B. J. A., Bax, H. I., Hassing, R. J., van der Feltz, M., Bassant, N., van Beek, J. E. A., Vriesde, M., van Zonneveld, L. M., de Oude-Lubbers, A., van den Berg-Cameron, H. J., Bruinsma-Broekman, F. B., de Groot, J., de Zeeuw- de Man, M., Broekhoven-Kruijne, M. J., Schutten, M., Osterhaus, A. D. M. E., Boucher, C. A. B., Driessen, G. J. A., van Rossum, A. M. C., van der Knaap, L. C., Visser, E., Branger, J., H. M. Duijf-van de Ven, C. J., Schippers, E. F., van Nieuwkoop, C., Brimicombe, R. W., van IJperen, J. M., van der Hut, G., Franck, P. F. H., van Eeden, A., Brokking, W., Groot, M., Damen, M., Kwa, I. S., Groeneveld, P. H. P., Bouwhuis, J. W., van den Berg, J. F., van Hulzen, A. G. W., van der Bliek, G. L., Bor, P. C. J., Bloembergen, P., Wolfhagen, M. J. H. M., Ruijs, G. J. H. M., van Lelyveld, S. F. L., Soetekouw, R., Hulshoff, N., van der Prijt, L. M. M., Schoemaker, M., Bermon, N., van der Reijden, W. A., Jansen, R., Herpers, B. L., Veenendaal, D., Kroon, F. P., Arend, S. M., de Boer, M. G. J., Bauer, M. P., Jolink, H., Vollaard, A. M., Dorama, W., Moons, C., Claas, E. C. J., Kroes, A. C. M., den Hollander, J. G., Pogany, K., Kastelijns, M., Smit, J. V., Smit, E., Bezemer, M., van Niekerk, T., Pontesilli, O., Lowe, S. H., Oude Lashof, A., Posthouwer, D., Ackens, R. P., Schippers, J., Vergoossen, R., Weijenberg Maes, B., Savelkoul, P. H. M., Loo, I. H., Weijer, S., El Moussaoui, R., Heitmuller, M., Kortmann, W., van Twillert, G., Cohen Stuart, J. W. T., Diederen, B. M. W., Pronk, D., van Truijen-Oud, F. A., Leyten, E. M. S., Gelinck, L. B. S., van Hartingsveld, A., Meerkerk, C., Wildenbeest, G. S., Mutsaers, J. A. E. M., Jansen, C. L., van Vonderen, M. G. A., van Houte, D. P. F., Dijkstra, K., Faber, S., Weel, J., Kootstra, G. J., Delsing, C. E., van der Burg-van de Plas, M., Heins, H., Lucas, E., Brinkman, K., Frissen, P. H. J., Blok, W. L., Schouten, W. E. M., Bosma, A. S., Brouwer, C. J., Geerders, G. F., Hoeksema, K., Kleene, M. J., van der Meché, I. B., Toonen, A. J. M., Wijnands, S., van Ogtrop, M. L., Koopmans, P. P., Keuter, M., van der Ven, A. J. A. M., ter Hofstede, H. J. M., Dofferhoff, A. S. M., van Crevel, R., Albers, M., Bosch, M. E. W., Grintjes-Huisman, K. J. T., Zomer, B. J., Stelma, F. F., Burger, D., Richter, C., van der Berg, J. P., Gisolf, E. H., ter Beest, G., van Bentum, P. H. M., Langebeek, N., Tiemessen, R., Swanink, C. M. A., Veenstra, J., Lettinga, K. D., Spelbrink, M., Sulman, H., Witte, E., Peerbooms, P. G. H., Mulder, J. W., Vrouenraets, S. M. E., Lauw, F. N., van Broekhuizen, M. C., Paap, H., Vlasblom, D. J., Oudmaijer Sanders, E., Smits, P. H. M., Rosingh, A. W., Verhagen, D. W. M., Geilings, J., van Kasteren, M. E. E., Brouwer, A. E., de Kruijf-van de Wiel, B. A. F. M., Kuipers, M., Santegoets, R. M. W. J., van der Ven, B., Marcelis, J. H., G. M. Buiting, A., Kabel, P. J., Bierman, W. F. W., Sprenger, H. G., Scholvinck, E. H., van Assen, S., Wilting, K. R., Stienstra, Y., de Groot-de Jonge, H., van der Meulen, P. A., de Weerd, D. A., Niesters, H. G. M., Riezebos-Brilman, A., van Leer-Buter, C. C., Hoepelman, A. I. M., Schneider, M. M. E., Mudrikova, T., Ellerbroek, P. M., Oosterheert, J. J., Arends, J. E., Barth, R. E., Wassenberg, M. W. M., van Elst-Laurijssen, D. H. M., Laan, L. M., van Oers-Hazelzet, E. E. B., Patist, J., Vervoort, S., Nieuwenhuis, H. E., Frauenfelder, R., Schuurman, R., Verduyn-Lunel, F., Wensing, A. M. J., Peters, E. J. G., van Agtmael, M. A., Perenboom, R. M., Bomers, M., de Vocht, J., Elsenburg, L. J. M., Pettersson, A. M., Vandenbroucke-Grauls, C. M. J. E., Ang, C. W., Geelen, S. P. M., Wolfs, T. F. W., Bont, L. J., Nauta, N., Bezemer, D. O., Gras, L., van Sighem, A. I., Smit, C., Zaheri, S., Kimmel, V., Tong, Y., Lascaris, B., van den Boogaard, R., Hoekstra, P., de Lang, A., Berkhout, M., Grivell, S., Jansen, A., de Groot, L., van den Akker, M., Bergsma, D., Lodewijk, C., Meijering, R., Peeck, B., Raethke, M., Ree, C., Regtop, R., Ruijs, Y., Schoorl, M., Tuijn, E., Veenenberg, L., Woudstra, T., Bakker, Y., de Jong, A., Broekhoven, M., Claessen, E., Rademaker, M. J., Munjishvili, L., Kruijne, E., Tuk, B., Bonnet, F., Dupon, M., Chêne, G., Breilh, D., Fleury, H., Malvy, D., Mercié, P., Pellegrin, I., Neau, D., Pellegrin, J. L., Bouchet, S., Gaborieau, V., Lacoste, D., Tchamgoué, S., Thiébaut, R., Lawson-Ayayi, S., Wittkop, L., Bernard, N., Hessamfar, M., Vandenhende, M. A., Dauchy, F. A., Dutronc, H., Longy-Boursier, M., Duffau, P., Roger Schmeltz, J., Pistone, T., Receveur, M. C., Cazanave, C., Ochoa, A., Vareil, M. O., Viallard, J. F., Greib, C., Lazaro, E., Lafon, M. E., Reigadas, S., Trimoulet, P., Molimard, M., Titier, K., Moreau, J. F., Haramburu, F., Miremont-Salamé, G., Dupont, A., Gerard, Y., Caunègre, L., André, K., Bonnal, F., Farbos, S., Gemain, M. C., Ceccaldi, J., De Witte, S., Courtault, C., Monlun, E., Lataste, P., Meraud, J. P., Chossat, I., Blaizeau, M. J., Conte, V., Decoin, M., Delaune, J., Delveaux, S., Diarra, F., D'Ivernois, C., Frosch, A., Hannapier, C., Lenaud, E., Leleux, O., Le Marec, F., Leray, J., Louis, I., Palmer, G., Pougetoux, A., Sicard, X., Touchard, D., Uwamaliya-Nziyumvira, B., Petoumenos, K., Bendall, C., Moore, R., Edwards, S., Hoy, J., Watson, K., Roth, N., Nicholson, J., Bloch, M., Franic, T., Baker, D., Vale, R., Carr, A., Cooper, D., Chuah, J., Ngieng, M., Nolan, D., Skett, J., Calvo, G., Mateu, S., Domingo, P., Sambeat, M. A., Gatell, J., Del Cacho, E., Cadafalch, J., Fuster, M., Codina, C., Sirera, G., Vaqué, A., Dewit, S., Clumeck, N., Necsoi, C., Gennotte, A. F., Gerard, M., Kabeya, K., Konopnicki, D., Libois, A., Martin, C., Payen, M. C., Semaille, P., Van Laethem, Y., Neaton, J., Bartsch, G., Thompson, G., Wentworth, D., Luskin-Hawk, R., Telzak, E., Abrams, D. I., Cohn, D., Markowitz, N., Arduino, R., Mushatt, D., Friedland, G., Perez, G., Tedaldi, E., Fisher, E., Gordin, F., Crane, L. R., Sampson, J., Baxter, J., Lundgren, J., Cozzi-Lepri, A., Grint, D., Podlekareva, D., Peters, L., Reekie, J., Fischer, A. H., Losso, M., Elias, C., Vetter, N., Zangerle, R., Karpov, I., Vassilenko, A., Mitsura, V. M., Suetnov, O., Colebunders, R., Vandekerckhove, L., Hadziosmanovic, V., Kostov, K., Begovac, J., Machala, L., Jilich, D., Sedlacek, D., Kronborg, G., Benfield, T., Larsen, M., Gerstoft, J., Katzenstein, T., Hansen, A. -B. E., Skinhøj, P., Pedersen, C., Ostergaard, L., Zilmer, K., Smidt, J., Ristola, M., Katlama, C., Viard, J. -P., Girard, P. -M., Livrozet, J. M., Vanhems, P., Rockstroh, J., Schmidt, R., van Lunzen, J., Degen, O., Stellbrink, H. J., Staszewski, S., Bickel, M., Kosmidis, J., Gargalianos, P., Xylomenos, G., Perdios, J., Panos, G., Filandras, A., Karabatsaki, E., Sambatakou, H., Banhegyi, D., Mulcahy, F., Yust, I., Turner, D., Burke, M., Pollack, S., Hassoun, G., Maayan, S., Vella, S., Esposito, R., Mazeu, I., Mussini, C., Arici, C., Pristera, R., Mazzotta, F., Gabbuti, A., Vullo, V., Lichtner, M., Chirianni, A., Montesarchio, E., Gargiulo, M., Antonucci, G., Testa, A., Narciso, P., Vlassi, C., Zaccarelli, M., Lazzarin, A., Castagna, A., Gianotti, N., Galli, M., Ridolfo, A., d’Arminio Monforte, A., Rozentale, B., Zeltina, I., Chaplinskas, S., Hemmer, R., Staub, T., Ormaasen, V., Maeland, A., Bruun, J., Knysz, B., Gasiorowski, J., Horban, A., Bakowska, E., Grzeszczuk, A., Flisiak, R., Boron-Kaczmarska, A., Pynka, M., Parczewski, M., Beniowski, M., Mularska, E., Trocha, H., Jablonowska, E., Malolepsza, E., Wojcik, K., Antunes, F., Doroana, M., Caldeira, L., Mansinho, K., Maltez, F., Duiculescu, D., Rakhmanova, A., Zakharova, N., Buzunova, S., Jevtovic, D., Mokráš, M., Staneková, D., Tomazic, J., González-Lahoz, J., Soriano, V., Labarga, P., Medrano, J., Moreno, S., Rodriguez, J. M., Clotet, B., Jou, A., Paredes, R., Tural, C., Puig, J., Bravo, I., Gatell, J. M., Miró, J. M., Gutierrez, M., Mateo, G., Karlsson, A., Flamholc, L., Ledergerber, B., Francioli, P., Cavassini, M., Hirschel, B., Boffi, E., Furrer, H., Battegay, M., Elzi, L., Kravchenko, E., Chentsova, N., Frolov, V., Kutsyna, G., Servitskiy, S., Krasnov, M., Barton, S., Johnson, A. M., Mercey, D., Johnson, M. A., Murphy, M., Weber, J., Scullard, G., Fisher, M., Leen, C., Morfeldt, L., Thulin, G., Åkerlund, B., Koppel, K., Håkangård, C., Moroni, M., Angarano, G., Antinori, A., Armignacco, O., Castelli, F., Cauda, R., Di Perri, G., Iardino, R., Ippolito, G., Perno, C. F., von Schloesser, F., Viale, P., Ceccherini-Silberstein, F., Girardi, E., Lo Caputo, S., Puoti, M., Andreoni, M., Ammassari, A., Balotta, C., Bonfanti, P., Bonora, S., Borderi, M., Capobianchi, R., Ceccherini- Silberstein, F., Cingolani, A., Cinque, P., De Luca, A., Di Biagio, A., Gori, A., Guaraldi, G., Lapadula, G., Madeddu, G., Maggiolo, F., Marchetti, G., Marcotullio, S., Monno, L., Quiros Roldan, E., Rusconi, S., Cicconi, P., Formenti, T., Galli, L., Lorenzini, P., Giacometti, A., Costantini, A., Santoro, C., Suardi, C., Vanino, E., Verucchi, G., Minardi, C., Quirino, T., Abeli, C., Manconi, P. E., Piano, P., Vecchiet, J., Falasca, K., Sighinolfi, L., Segala, D., Cassola, G., Viscoli, G., Alessandrini, A., Piscopo, R., Mazzarello, G., Mastroianni, C., Belvisi, V., Caramma, I., Castelli, A. P., Rizzardini, G., Ridolfo, A. L., Piolini, R., Salpietro, S., Carenzi, L., Moioli, M. C., Puzzolante, C., Abrescia, N., Guida, M. G., Onofrio, M., Baldelli, F., Francisci, D., Parruti, G., Ursini, T., Magnani, G., Ursitti, M. A., D’Avino, A., Gallo, L., Nicastri, E., Acinapura, R., Capozzi, M., Libertone, R., Tebano, G., Cattelan, A., Mura, M. S., Caramello, P., Orofino, G. C., Sciandra, M., Pellizzer, G., Manfrin, V., Dollet, K., Caissotti, C., Dellamonica, P., Roger, P. M., Bernard, E., Cua, E., De Salvador-Guillouet, F., Durant, J., Ferrando, S., Dunais, B., Mondain-Miton, V., Perbost, I., Prouvost-Keller, B., Pugliese, P., Naqvi, A., Pillet, S., Risso, K., Aubert, V., Barth, J., Bernasconi, E., Böni, J., Bucher, H. C., Burton-Jeangros, C., Calmy, A., Egger, M., Fehr, J., Fellay, J., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, H. H., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kovari, H., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, A., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Taffé, P., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Yerly, S., Bhagani, S., Burns, F., Byrne, P., Carroll, A., Cropley, I., Cuthbertson, Z., Drinkwater, T., Fernandez, T., Garusu, E., Gonzales, A., Grover, D., Hutchinson, S., Killingley, B., Murphy, G., Ivens, D., Johnson, M., Kinloch de Loes, S., Lipman, M., Madge, S., Marshall, N., Montgomery, H., Shah, R., Swaden, L., Tyrer, M., Youle, M., Webster, D., Wright, A., Chaloner, C., Miah, M., Tsintas, R., Burch, L., Cambiano, V., Lampe, F., Nakagawa, F., O'Connor, J., Speakman, A., Connell, M., Clewley, G., Martin, S., Thomas, M., Aagaard, B., Aragon, E., Arnaiz, J., Borup, L., Dragsted, U., Fau, A., Gey, D., Grarup, J., Hengge, U., Herrero, P., Jansson, P., Jensen, B., Jensen, K., Juncher, H., Lopez, P., Matthews, C., Mollerup, D., Pearson, M., Reilev, S., Tillmann, K., Varea, S., Angus, B., Babiker, A., Cordwell, B., Darbyshire, J., Dodds, W., Fleck, S., Horton, J., Hudson, F., Moraes, Y., Pacciarini, F., Palfreeman, A., Paton, N., Smith, N., van Hooff, F., Bebchuk, J., Collins, G., Denning, E., Duchene, A., Fosdick, L., Harrison, M., Herman-Lamin, K., Larson, G., Nelson, R., Quan, K., Quan, S., Schultz, T., Wyman, N., Carey, C., Chan, F., Courtney-Rodgers, D., Drummond, F., Emery, S., Harrod, M., Jacoby, S., Kearney, L., Lin, E., Pett, S., Robson, R., Seneviratne, N., Stewart, M., Watts, E., Finley, E., Sánchez, A., Standridge, B., Vjecha, M., Belloso, W., Davey, R., Duprez, D., Lifson, A., Pederson, C., Price, R., Prineas, R., Rhame, F., Worley, J., Modlin, J., Beral, V., Chaisson, R., Fleming, T., Hill, C., Kim, K., Murray, B., Pick, B., Seligmann, M., Weller, I., Cahill, K., Fox, L., Luzar, M., Martinez, A., Mcnay, L., Pierson, J., Tierney, J., Vogel, S., Costas, V., Eckstrand, J., Brown, S., Abusamra, L., Angel, E., Aquilia, S., Benetucci, J., Bittar, V., Bogdanowicz, E., Cahn, P., Casiro, A., Contarelli, J., Corral, J., Daciuk, L., David, D., Dobrzanski, W., Duran, A., Ebenrstejin, J., Ferrari, I., Fridman, D., Galache, V., Guaragna, G., Ivalo, S., Krolewiecki, A., Lanusse, I., Laplume, H., Lasala, M., Lattes, R., Lazovski, J., Lopardo, G., Lourtau, L., Lupo, S., Maranzana, A., Marson, C., Massera, L., Moscatello, G., Olivia, S., Otegui, I., Palacios, L., Parlante, A., Salomon, H., Sanchez, M., Somenzini, C., Suarez, C., Tocci, M., Toibaro, J., Zala, C., Agrawal, S., Ambrose, P., Anderson, C., Anderson, J., Beileiter, K., Blavius, K., Boyle, M., Bradford, D., Britton, P., Brown, P., Busic, T., Cain, A., Carrall, L., Carson, S., Chenoweth, I., Clark, F., Clemons, J., Clezy, K., Cortissos, P., Cunningham, N., Curry, M., Daly, L., D'Arcy-Evans, C., Del Rosario, R., Dinning, S., Dobson, P., Donohue, W., Doong, N., Downs, C., Edwards, E., Egan, C., Ferguson, W., Finlayson, R., Forsdyke, C., Foy, L., Frater, A., French, M., Gleeson, D., Gold, J., Habel, P., Haig, K., Hardy, S., Holland, R., Hudson, J., Hutchison, R., Hyland, N., James, R., Johnston, C., Kelly, M., King, M., Kunkel, K., Lau, H., Leamy, J., Lester, D., Leung, J., Lohmeyer, A., Lowe, K., Macrae, K., Magness, C., Martinez, O., Maruszak, H., Medland, N., Miller, S., Murray, J., Negus, P., Newman, R., Nowlan, C., Oddy, J., Orford, N., Orth, D., Patching, J., Plummer, M., Price, S., Primrose, R., Prone, I., Ree, H., Remington, C., Richardson, R., Robinson, S., Rogers, G., Roney, J., Russell, D., Ryan, S., Sarangapany, J., Schmidt, T., Schneider, K., Shields, C., Silberberg, C., Shaw, D., Smith, D., Meng Soo, T., Sowden, D., Street, A., Kiem Tee, B., Thomson, J. L., Topaz, S., Villella, C., Walker, A., Watson, A., Wendt, N., Williams, L., Youds, D., Aichelburg, A., Cichon, P., Gemeinhart, B., Rieger, A., Schmied, B., Touzeau-Romer, V., Deroo, A., O'Doherty, E., de Wit, S., De Salles Amorim, C., Basso, C., Flint, S., Kallas, E., Levi, G., Lewi, D., Pereira, L., da Silva, M., Souza, T., Toscano, A., Angel, J., Arsenault, M., Bast, M., Beckthold, B., Bouchard, P., Chabot, I., Clarke, R., Cohen, J., Coté, P., Ellis, M., Gagne, C., Gill, J., Houde, M., Johnston, B., Jubinville, N., Kato, C., Lamoureux, N., Latendre-Paquette, J., Lindemulder, A., Mcneil, A., Mcfarland, N., Montaner, J., Morrisseau, C., O'Neill, R., Page, G., Piche, A., Pongracz, B., Preziosi, H., Puri, L., Rachlis, A., Ralph, E., Raymond, I., Rouleau, D., Routy, J. P., Sandre, R., Seddon, R. 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D., Beers, D., Beilke, M., Bemenderfer, D., Bernard, A., Besch, C. L., Bessesen, M. T., Bethel, J. T., Blue, S., Blum, J. D., Boarden, S., Bolan, R. K., Borgman, J. B., Brar, I., Braxton, B. K., Bredeek, U. F., Brennan, R., Britt, D. E., Bulgin-Coleman, D., Bullock, D. E., Campbell, B., Caras, S., Carroll, J., Casey, K. K., Chiang, F., Cindrich, R. B., Clark, C., Cohen, C., Coley, J., Condoluci, D. V., Contreras, R., Corser, J., Cozzolino, J., Daley, L., Dandridge, D., D'Antuono, V., Darcourt Rizo Patron, J. G., Dehovitz, J. A., Dejesus, E., Desjardin, J., Dietrich, C., Dolce, E., Erickson, D., Faber, L. L., Falbo, J., Farrough, M. J., Farthing, C. F., Ferrell-Gonzalez, P., Flynn, H., Frank, M., Freeman, K. F., French, N., Fujita, N., Gahagan, L., Gilson, I., Goetz, M. B., Goodwin, E., Guity, C. K., Gulick, P., Gunderson, E. R., Hale, C. M., Hannah, K., Henderson, H., Hennessey, K., Henry, W. K., Higgins, D. T., Hodder, S. L., Horowitz, H. W., Howe-Pittman, M., Hubbard, J., Hudson, R., Hunter, H., Hutelmyer, C., Insignares, M. T., Jackson, L., Jenny, L., Johnson, D. L., Johnson, G., Johnson, J., Kaatz, J., Kaczmarski, J., Kagan, S., Kantor, C., Kempner, T., Kieckhaus, K., Kimmel, N., Klaus, B. M., Koeppe, J. R., Koirala, J., Kopka, J., Kostman, J. R., Kozal, M. J., Kumar, A., Lampiris, H., Lamprecht, C., Lattanzi, K. M., Lee, J., Leggett, J., Long, C., Loquere, A., Loveless, K., Lucasti, C. J., Macveigh, M., Makohon, L. H., Markowitz, N. P., Marks, C., Martorell, C., Mcfeaters, E., Mcgee, B., Mcintyre, D. M., Mcmanus, E., Melecio, L. G., Melton, D., Mercado, S., Merrifield, E., Mieras, J. A., Mogyoros, M., Moran, F. M., Murphy, K., Mutic, S., Nadeem, I., Nadler, J. P., Ognjan, A., O'Hearn, M., O'Keefe, K., Okhuysen, P. C., Oldfield, E., Olson, D., Orenstein, R., Ortiz, R., Parpart, F., Pastore-Lange, V., Paul, S., Pavlatos, A., Pearce, D. D., Pelz, R., Peterson, S., Pitrak, D., Powers, S. L., Pujet, H. C., Raaum, J. W., Ravishankar, J., Reeder, J., Reilly, N. A., Reyelt, C., Riddell, J., Rimland, D., Robinson, M. L., Rodriguez, A. E., Rodriguez-Barradas, M. C., Rodriguez Derouen, V., Rosmarin, C., Rossen, W. L., Rouff, J. R., Sampson, J. H., Sands, M., Savini, C., Schrader, S., Schulte, M. M., Scott, R., Seedhom, H., Sension, M., Sheble-Hall, A., Shuter, J., Slater, L. N., Slotten, R., Smith, M., Snap, S., States, D. M., Stringer, G., Summers, K. K., Swanson, K., Sweeton, I. B., Szabo, S., Tedaldi, E. M., Telzak, E. E., Thompson, M. A., Thompson, S., Ting Hong Bong, C., Vaccaro, A., Vasco, L. M., Vecino, I., Verlinghieri, G. K., Visnegarwala, F., Wade, B. H., Weis, S. E., Weise, J. A., Weissman, S., Wilkin, A. M., Witter, J. H., Wojtusic, L., Wright, T. J., Yeh, V., Young, B., Zeana, C., Zeh, J., Savio, E., Vacarezza, M., University College of London [London] (UCL), University of Copenhagen = Københavns Universitet (KU), University of New South Wales [Sydney] (UNSW), University of Amsterdam [Amsterdam] (UvA), University of Minnesota [Twin Cities] (UMN), University of Minnesota System, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nice (CHU Nice), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Med Microbiol, Infect Dis & Infect Prev, RS: NUTRIM - R3 - Chronic inflammatory disease and wasting, RS: CAPHRI School for Public Health and Primary Care, RS: CAPHRI - R4 - Health Inequities and Societal Participation, Interne Geneeskunde, Chemical Biology, Mocroft, A, Lundgren, J, Ross, M, Law, M, Reiss, P, Kirk, O, Smith, C, Wentworth, D, Neuhaus, J, Fux, C, Moranne, O, Morlat, P, Johnson, M, Ryom, L, Gori, A, Internal medicine, CCA - Innovative therapy, ICaR - Circulation and metabolism, Medical Microbiology and Infection Prevention, CCA - Disease profiling, CCA - Immuno-pathogenesis, Plastic, Reconstructive and Hand Surgery, Mocroft, Amanda, Lundgren, Jens D., Ross, Michael, Law, Matthew, Reiss, Peter, Kirk, Ole, Smith, Colette, Wentworth, Deborah, Neuhaus, Jacqueline, Fux, Christoph A., Moranne, Olivier, Morlat, Phillipe, Johnson, Margaret A., Ryom, Lene, D:a:d Study, Group, Castagna, Antonella, the Royal Free Hospital Clinic, Cohort, and the, Insight, Smart, and ESPRIT, Study, Clinicum, Department of Medicine, Herrada, Anthony, University of Copenhagen = Københavns Universitet (UCPH), AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, Global Health, Other departments, Infectious diseases, Paediatric Infectious Diseases / Rheumatology / Immunology, General Internal Medicine, Center of Experimental and Molecular Medicine, Graduate School, Gastroenterology and Hepatology, Dermatology, ACS - Amsterdam Cardiovascular Sciences, Other Research, Anesthesiology, and Bartlett, John
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Male ,Adult ,Age Factors ,Anti-HIV Agents ,CD4 Lymphocyte Count ,Clinical Decision-Making ,Comorbidity ,Female ,HIV ,HIV Infections ,HIV Seropositivity ,Humans ,Incidence ,Kidney ,Middle Aged ,Prospective Studies ,Renal Insufficiency, Chronic ,Risk ,Risk Assessment ,Sex Factors ,urologic and male genital diseases ,Biochemistry ,0302 clinical medicine ,ANTIRETROVIRAL THERAPY ,Adult, Age Factors, Anti-HIV Agents, CD4 Lymphocyte Count, Clinical Decision-Making, Comorbidity, Female, HIV, HIV Infections, HIV Seropositivity, Humans, Incidence, Kidney, Male, Middle Aged, Prospective Studies, Renal Insufficiency, Chronic, Risk, Risk Assessment, Sex Factors ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Age Factor ,Chronic ,STAGE RENAL-DISEASE ,PROTEINURIA ,virus diseases ,11 Medical And Health Sciences ,General Medicine ,ASSOCIATION ,6. Clean water ,female genital diseases and pregnancy complications ,3. Good health ,HIV/AIDS ,Medicine ,Infection ,psychological phenomena and processes ,Human ,medicine.medical_specialty ,Renal function ,NEFROPATIAS ,chronic kidney disease ,risk score model ,12. Responsible consumption ,ESPRIT study group ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Clinical Research ,D:A:D study group ,Intensive care medicine ,medicine (all) ,Molecular Biology ,Royal Free Hospital Clinic Cohort ,Prevention ,Anti-HIV Agent ,medicine.disease ,Prospective Studie ,lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] ,Immunology ,Kidney Disease ,PREDICTION ,POSITIVE PERSONS ,030232 urology & nephrology ,Sex Factor ,SDG 3 – Goede gezondheid en welzijn ,Medical and Health Sciences ,GLOMERULAR-FILTRATION-RATE ,[SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology ,INSIGHT study group ,HIV Infection ,LIFE EXPECTANCY ,030212 general & internal medicine ,Renal Insufficiency ,Prospective cohort study ,Framingham Risk Score ,Incidence (epidemiology) ,adult ,age factors ,anti-hiv agents ,CD4 lymphocyte count ,clinical decision-making ,comorbidity ,female ,hiv ,hiv infections ,hiv seropositivity ,humans ,incidence ,kidney ,male ,middle aged ,prospective studies ,renal insufficiency, chronic ,risk ,risk assessment ,sex factors ,SMART study group ,6.1 Pharmaceuticals ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Patient Safety ,Risk assessment ,Biotechnology ,Research Article ,Settore MED/17 - MALATTIE INFETTIVE ,NO ,A:D study group [D] ,General & Internal Medicine ,Diabetes mellitus ,mental disorders ,medicine ,EXPOSURE ,business.industry ,Evaluation of treatments and therapeutic interventions ,Cell Biology ,[SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology ,INDIVIDUALS ,Good Health and Well Being ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,3121 General medicine, internal medicine and other clinical medicine ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,business ,Kidney disease - Abstract
Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with ≥3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR ≤ 60 ml/min/1.73 m2. Poisson regression was used to develop a risk score, externally validated on two independent cohorts. In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7–6.7; median follow-up 6.1 y, range 0.3–9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was −2 (interquartile range –4 to 2). There was a 1:393 chance of developing CKD in the next 5 y in the low risk group (risk score < 0, 33 events), rising to 1:47 and 1:6 in the medium (risk score 0–4, 103 events) and high risk groups (risk score ≥ 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166–3,367); NNTH was 202 (95% CI 159–278) and 21 (95% CI 19–23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506–1462), 88 (95% CI 69–121), and 9 (95% CI 8–10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3–12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6–8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD., Editors’ Summary Background About 35 million people are currently infected with HIV, the virus that causes AIDS. HIV destroys CD4 lymphocytes and other immune system cells, leaving infected individuals susceptible to other infections. HIV infection can be controlled, but not cured, using combination antiretroviral therapy (cART), and, nowadays, the life expectancy of many HIV-positive individuals is similar to that of HIV-negative people. HIV-positive individuals nevertheless experience some illnesses more frequently than HIV-negative people do. For example, up to a third of HIV-positive individuals develop chronic kidney disease (CKD), which is associated with an increased risk of cardiovascular disease and death. Persons with CKD may have an impaired effect of the filtration units in the kidneys that remove waste products and excess water from the blood to make urine, thereby leading to a reduced blood filtration rate (the estimated glomerular filtration rate [eGFR]) and waste product accumulation in the blood. Symptoms of CKD, which rarely occur until the disease is advanced, include tiredness, swollen feet, and frequent urination. Advanced stages of CKD cannot be cured, but its progression can be slowed by, for example, controlling hypertension (high blood pressure) and diabetes (two CDK risk factors) and by adopting a healthy lifestyle. Why Was This Study Done? The burden of CKD may increase among HIV-positive individuals as they age, and clinicians need to know which individuals are at high risk of developing CKD when choosing cART regimens for their patients. In addition, clinicians need to be able to identify those HIV-positive individuals at greatest risk of CKD so that they can monitor them for early signs of kidney disease. Some antiretroviral drugs—for example, tenofovir and atazanavir/ritonavir (a boosted protease inhibitor)—are associated with kidney damage. Clinicians may need to weigh the benefits and risks of giving such potentially nephrotoxic drugs to individuals who already have a high CKD risk. Here, the researchers develop and validate a simple, widely applicable risk score (a risk prediction model) for CKD among HIV-positive individuals and investigate the relationship between CKD and potentially nephrotoxic antiretroviral drugs among individuals with different CKD risk score profiles. What Did the Researchers Do and Find? To develop their CKD risk score, the researchers used clinical and demographic data collected from 17,954 HIV-positive individuals enrolled in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study who had an eGFR > 60 ml/min/1.73 m2 and were not taking a potentially nephrotoxic antiretroviral at baseline. During 103,185 person-years of follow-up, 641 individuals developed CKD. Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease predicted CKD. The researchers included these nine factors in their risk score model (which is available online) and defined three risk groups: low (risk score < 0), medium (risk score 0–4), and high (risk score ≥ 5) risk of CKD development in the next five years. Specifically, there was a 1 in 393, 1 in 47, and 1 in 6 chance of developing CKD in the next five years in the low, medium, and high risk groups, respectively. Because some patients started to use potentially nephrotoxic antiretroviral drugs during follow-up, the researchers were able to use their risk score model to calculate how many patients would have to be treated with one of these drugs for an additional patient to develop CKD over five years in each risk group. This “number needed to harm” (NNTH) for patients starting treatment with tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor was 739, 88, and 9 in the low, medium, and high risk groups, respectively. Finally, the researchers validated the accuracy of their risk score in two independent HIV study groups. What Do These Findings Mean? These findings provide a simple, validated risk score for CKD and indicate that the NNTH when starting potentially nephrotoxic antiretrovirals was low among HIV-positive individuals at the highest risk of CKD (i.e., treating just nine individuals with nephrotoxic antiretroviral drugs will likely lead to an additional case of CKD in five years). Although various aspects of the study, including the lack of data on race, limit the accuracy of these findings, these findings highlight the need for monitoring, screening, and chronic disease prevention to minimize the risk of HIV-positive individuals developing diabetes, hypertension, or cardiovascular disease, or becoming coinfected with hepatitis C, all of which contribute to the CKD risk score. Moreover, the development of a tool for estimating an individual’s five-year risk of developing CKD with or without the addition of potentially nephrotoxic antiretroviral drugs will enable clinicians and patients to weigh the benefits of certain antiretroviral drugs against the risk of CKD and make informed decisions about treatment options. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001809. Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS NAM/aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and personal stories about living with AIDS/HIV Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including personal stories about living with HIV/AIDS The World Health Organization provides information on all aspects of HIV/AIDS (in several languages), including its guidelines on the use of ART for treating and preventing HIV infection The UNAIDS World AIDS Day Report 2014 provides up-to-date information about the AIDS epidemic and efforts to halt it The UK National Health Service Choices website provides information for patients on chronic kidney disease, including some personal stories The US National Kidney Foundation, a not-for-profit organization, provides information about chronic kidney disease (in English and Spanish) A tool for calculating the CDK risk score developed in this study is available Additional information about the D:A:D study is available, Amanda Mocroft and colleagues develop and validate a model for determining risk of developing chronic kidney disease for individuals with HIV if treated with different antiretroviral therapies.
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- 2015
7. Termination of Newton/Chord Iterations and the Method of Lines
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Miller, C. T., Kelley, C. T., and Tocci, M. D.
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- 1998
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8. Characterization of a New Aluminium Alloy for the Production of Wheels by Hybrid Aluminium Forging.
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Tocci, M., Pola, A., La Vecchia, G.M., and Modigell, M.
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ALUMINUM alloys ,ALUMINUM forgings ,CASTING (Manufacturing process) ,CHEMICAL processes ,TENSILE strength - Abstract
Recently, an innovative technique called Hybrid Aluminium Forging (HAF) has been developed as a combination of casting and forging processes. In the present paper the characterization of a new Al-Si-Mg alloy with Cr addition is reported; it was used in a preliminary study to evaluate its suitability for the production of wheels by HAF process. At first, calorimetric analysis was performed to identify solid fraction change with temperature for process optimization. The alloy after heat treatment shows good strength and hardness, but poor ductility, while Cr modifies the morphology of Fe-containing intermetallics. Finally, rheological measurements show a shear thinning behaviour of metal in semi-solid condition. [ABSTRACT FROM AUTHOR]
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- 2015
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9. Recent advances in the mechanism of action of cyclosporine and FK506.
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Tocci, Michael J., Sigal, Nolan H., Tocci, M J, and Sigal, N H
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- 1992
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10. Li/ Li1+xV3O8 secondary batteries. IV°. Evaluation of factors affecting the performance of test cells
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Pistoia, G., Pasquali, Mauro, Tocci, M., Manev, V., and Moshtev, R.
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Secondary lithium batteries ,Secondary lithium batteries, LiV3O8 as cathode ,LiV3O8 as cathode - Published
- 1985
11. THE FILM: A FEW GOOD MEN THE LESSON: JURORS GIVE THEIR OWN MEANING TO THE DIFFERENT WAYS THAT MEN AND WOMEN EXPRESS THEMSELVES.
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Tocci, M. J.
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LAWYERS , *EXAMINATION of witnesses , *WITNESSES , *CROSS-examination , *LEGAL judgments , *LAW firms , *LEGAL services , *ACTIONS & defenses (Law) - Abstract
The article focuses on the lessons learned by lawyers from the movie "A Few Good Men" that could help them manage their legal professions in the U.S. It mentions that conversational style is one of the most important factors in the cross-examination of the witness. It states that conversational style can affect the witness's credibility that influenced the judge's preparation of the witness, direct examination strategy and the use of closing arguments in addressing possible misunderstanding by the jury of the witness's testimony.
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- 2008
12. Critical clues in the cbc count.
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TOCCI M
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- 2010
13. Lithium/lithium vanadium oxide secondary batteries: IV. Evaluation of factors affecting the performance of test cells
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Pistola, G., Pasquali, M., Tocci, M., Manev, V., and Moshtev, R.V.
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- 1985
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14. Solid solutions Li 1+ xV 3O 8 as cathodes for high rate secondary Li batteries
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Pistoia, G., Panero, S., Tocci, M., Moshtev, R.V., and Manev, V.
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- 1984
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15. Thermodynamic study of lithium insertion in V 6O 13 and Li 1+ xV 3O 8
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Pistoia, G., Rodante, F., and Tocci, M.
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- 1986
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16. Calorimetric study of some α-amino acids in water at 25°C
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Rodante, F. and Tocci, M.
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- 1985
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17. Calorimetric study of the ionization process for 2,5-dihydroxybenzoic acid. Resonance effect. A calorimetric acidity scale for dihydroxy-substituted benzoic derivatives
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Rodante, F., Tocci, M., and Onofri, A.
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- 1985
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18. On the use of nonylbenzo-hexaquinone as a substitute for monomeric quinones in non-aqueous cells
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Boschi, T., Pappa, R., Pistoia, G., and Tocci, M.
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- 1984
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19. The reduction of polycondensed quinones from hydroquinone, phenol and formaldehyde in Li +-containing organic solutions
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Boschi, T., Pappa, R., Pistola, G., and Tocci, M.
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- 1985
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20. Mechanical spectroscopy study of as-cast and additive manufactured AlSi10Mg.
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Cabibbo, M., Montanari, R., Pola, A., Tocci, M., and Varone, A.
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SUPERSATURATED solutions , *MICROSCOPY , *SPECTROMETRY , *HYPEREUTECTIC alloys , *DISLOCATION density , *CELL morphology - Abstract
The AlSi10Mg alloy produced by casting (AC) and additive manufacturing (AM) technology of laser powder bed fusion (L -PBF) has been investigated through mechanical spectroscopy (MS). In addition to the grain boundary peak P GB the Q −1 curves of both materials exhibit two other relaxation peaks, P1 (H = 0.8 ± 0.05 eV; τ 0 = 10−11±1 s) and P2 (H = 1.0 ± 0.05 eV; τ 0 = 10−13±1 s), depending on the interaction of dislocations with solute elements (Si and Mg). Relaxation strengths of P1, P2 and P GB of AM alloy are greater than those of the AC one owing to the finer structure of Al cells and the higher amount of Si and Mg in supersaturated solid solution induced by the rapid solidification typical of the L -PBF process. After successive MS test runs relaxation strengths of P1 and P2 peaks in both the examined materials decrease due to the precipitation of Si atoms and dislocation density recovery. Such decrease is more pronounced in AM alloy where change of cell shape and increase of cell size is observed. Dynamic modulus of AM alloy exhibits an anomalous trend in the first test run that is no more present in successive runs. The irreversible process giving rise to such anomalous behavior is the closure of pores of nanometric size. • AlSi10Mg produced by casting (AC) and additive manufacturing (AM) has been investigated through mechanical spectroscopy (MS). • Q-1 curves of both materials exhibit the grain boundary peak P GB and two other relaxation peaks (P1 and P2). • The MS results have been correlated to microstructural information from light microscopy, XRD, TEM and SEM. • The P1 and P2 peaks depend on the interaction of dislocations with solute elements (Si and Mg). • Dynamic modulus of AM alloy exhibits an anomalous trend in the first test run that is no more present in successive runs. [ABSTRACT FROM AUTHOR]
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- 2022
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21. Effects of the β3-adrenoceptor (Adrb3) agonist SR58611A (amibegron) on serotonergic and noradrenergic transmission in the rodent: Relevance to its antidepressant/anxiolytic-like profile
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Claustre, Y., Leonetti, M., Santucci, V., Bougault, I., Desvignes, C., Rouquier, L., Aubin, N., Keane, P., Busch, S., Chen, Y., Palejwala, V., Tocci, M., Yamdagni, P., Didier, M., Avenet, P., Le Fur, G., Oury-Donat, F., Scatton, B., and Steinberg, R.
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ADRENERGIC receptors , *SEROTONINERGIC mechanisms , *NORADRENERGIC neurons , *ANTIDEPRESSANTS - Abstract
Abstract: SR58611A is a selective β3-adrenoceptor (Adrb3) agonist which has demonstrated antidepressant and anxiolytic properties in rodents. The present study confirmed the detection of Adrb3 mRNA transcript in rodent brain sub-regions and evaluated the effect of SR58611A on serotonergic and noradrenergic transmission in rats and mice in an attempt to elucidate the mechanism(s) underlying these properties. SR58611A (3 and 10 mg/kg, p.o.) increased the synthesis of 5-HT and tryptophan (Trp) levels in several rodent brain areas (cortex, hippocampus, hypothalamus, striatum). Moreover, SR58611A (10 mg/kg, p.o.) increased the release of 5-HT assessed by in vivo microdialysis in rat prefrontal cortex. Systemic (3 mg/kg, i.v.) or chronic administration of SR58611A (10 mg/kg, p.o.), in contrast to fluoxetine (15 mg/kg, p.o.), did not modify the activity of serotonergic neurons in the rat dorsal raphe nucleus. The increase in 5-HT synthesis induced by SR58611A was not observed in Adrb3s knockout mice, suggesting a selective involvement of Adrb3s in this effect. SR58611A (3 and 10 mg/kg, p.o.) did not modify norepinephrine synthesis and metabolism but increased its release in rat brain. Repeated administration of SR58611A (10 mg/kg, p.o.) did not modify basal norepinephrine release in rat prefrontal cortex whereas it prevented its tail-pinch stress-induced enhancement similarly to reboxetine (15 mg/kg, p.o.). Finally SR58611A increased the firing rate of noradrenergic neurons in the rat locus coeruleus following systemic (3 mg/kg, i.v.) or local (0.01 and 1 μM) but not chronic (10 mg/kg, p.o.) administration. These results suggest that the anxiolytic- and antidepressant-like activities of SR58611A involve an increase of brain serotonergic and noradrenergic neurotransmissions, triggered by activation of Adrb3s. [Copyright &y& Elsevier]
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- 2008
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22. Transcatheter Aortic Valve Replacement in Low Surgical Risk Patients: An Updated Metanalysis of Extended Follow-Up Randomized Controlled Trials.
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Di Pietro G, Improta R, De Filippo O, Bruno F, Birtolo LI, Tocci M, Fabris T, Saade W, Colantonio R, Celli P, Sardella G, Esposito G, Tarantini G, Mancone M, and D'Ascenzo F
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- Humans, Follow-Up Studies, Postoperative Complications epidemiology, Risk Assessment methods, Risk Factors, Aortic Valve Stenosis surgery, Randomized Controlled Trials as Topic, Transcatheter Aortic Valve Replacement methods
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The long-term safety and effectiveness of transcatheter aortic valve replacement (TAVR) compared with surgical aortic valve replacement (SAVR) in low surgical risk has not been evaluated in a pooled analysis. An electronic database search was conducted for randomized controlled trials with a maximal 5 years clinical and echocardiographic follow-up including low surgical risk patients who underwent TAVR or SAVR. We calculated odds ratio (OR) and 95% confidence intervals (CIs) using a random-effects model. Subgroups analysis was performed for permanent pacemaker implantation and paravalvular leaks. Three randomized controlled trials were included with a total of 2,611 low surgical risk patients (Society of Thoracic Surgeons score <4%). Compared with SAVR, the TAVR group had similar rates of all-cause mortality (OR 0.94,95% CI 0.65 to 1.37, p = 0.75) and disabling stroke (OR 0.84, 95% CI 0.52 to 1.36, p = 0.48). No significant differences were registered in the TAVR group in terms of major cardiovascular events (OR 0.96, 95% CI 0.67 to 1.38, p = 0.83), myocardial infarction (OR 0.69, 95% CI 0.34 to 1.40, p = 0.31), valve thrombosis (OR 3.11, 95% CI 0.29 to 33.47, p = 0.35), endocarditis (OR 0.71,95% CI 0.35 to 1.48, p = 0.36), aortic valve reintervention (OR 0.93, 95% CI 0.52 to 1.66, p = 0.80), and rehospitalization (OR 0.80, 95% CI 0.52 to 1.02, p = 0.07) compared with SAVR. However, TAVR patients had a higher risk of paravalvular leaks (OR 8.21, 95% CI 4.18 to 16.14, p <0.00001), but lower rates of new-onset atrial fibrillation (OR 0.27,95% CI 0.17 to 0.30, p <0.0001). The rates of permanent pacemaker implantation were comparable from 1 year up to a maximum of 5 years (OR 1.32, 95% CI 0.88 to 1.97, p = 0.18). Lastly, TAVR had a greater effective orifice area (0.10 cm
2 /m2 , 95% CI 0.05 to 0.15, p = 0.0001), but similar transvalvular mean gradients (0.60, 95% CI 3.94 to 2.73, p = 0.72). In conclusion, TAVR patients had similar long-term outcomes compared with SAVR, except for an elevated risk of paravalvular leaks in the TAVR group and increased rates of atrial fibrillation in the SAVR cohort., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)- Published
- 2024
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23. Invasive and conservative management of elderly patients presenting with acute coronary syndrome: A meta-analysis of randomized controlled trials and adjusted observational studies.
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Improta R, Di Pietro G, Piccialuti A, De Filippo O, Birtolo LI, Severino P, Tocci M, Saade W, Cammertoni F, Vizza CD, Sardella G, D'Ascenzo F, Stefanini G, and Mancone M
- Subjects
- Humans, Aged, Percutaneous Coronary Intervention methods, Disease Management, Acute Coronary Syndrome therapy, Acute Coronary Syndrome mortality, Acute Coronary Syndrome diagnosis, Randomized Controlled Trials as Topic methods, Conservative Treatment methods, Observational Studies as Topic methods
- Abstract
Background: Elderly patients are often under-represented in studies about coronary revascularization in acute coronary syndromes (ACS) and undertreated in clinical practice. We sought to evaluate differences in outcomes between an initial invasive or conservative strategy in this subset of patients, METHODS: The analysis was performed following PRISMA guidelines. Randomized controlled trials (RCTs) and adjusted observational studies comparing an invasive and conservative strategy in old patients with ACS were systematically identified. Random or fixed effect model was used accordingly to heterogeneity testing results. Short-term mortality was the primary outcome. 30-day and longer-term re-infarction, MACE and all-cause mortality were secondary endpoints. Sensitivity analysis including RCTs only were performed for the primary endpoint and 1 year mortality and another analysis, stratifying NSTEMI and STEMI studies, was performed for short-term mortality., Results: Invasive management was associated with lower short and long-term mortality (30 days OR 0.64, 95 % CI 0.54-0.76, p < 0.001; 1 year HR 0.60, 95 % CI 0.52-0.78, p < 0.001; Long-term HR 0.62, 95 % CI 0.55-0.71, p < 0.001) compared to a conservative strategy. In the short-term follow-up, the benefit was preserved when differentiating for NSTEMI or STEMI studies but not when considering only RCTs. Major bleedings were more frequent in the invasive group (30 days OR 1.61, 95 % CI 1.39-1.87, p < 0.001). The mean difference in length of stay was not significantly different between the two strategies (mean difference in days 0.14, 95 % CI -0.79 to 1.06, p = 0.77)., Conclusion: An initial invasive strategy might lead to reduced short and long-term mortality in elderly patients presenting with acute coronary syndrome but it is associated with increased bleeding events rate. No difference in hospital stay length was observed. Results were mainly driven by non-randomized studies., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2024
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24. Characterization and Management of Stable Coronary Artery Disease in Patients Undergoing Transcatheter Aortic Valve Implantation.
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Sammartino S, Laterra G, Pilgrim T, Amat Santos IJ, De Backer O, Kim WK, Ribeiro HB, Saia F, Bunc M, Tchetche D, Garot P, Ribichini FL, Mylotte D, Burzotta F, Watanabe Y, Bedogni F, Tesorio T, Rheude T, Sardella G, Tocci M, Franzone A, Valvo R, Savontaus M, Wienemann H, Porto I, Gandolfo C, Iadanza A, Bortone AS, Mach M, Latib A, Biasco L, Taramasso M, De Marco F, Frittitta V, Dipietro E, Reddavid C, Strazzieri O, Motta S, Comis A, Melfa C, Calì M, Sgroi C, Abdel-Wahab M, Stefanini G, Tamburino C, Barbanti M, and Costa G
- Abstract
Background/Objectives : To date, data regarding the characteristics and management of obstructive, stable coronary artery disease (CAD) encountered in patients undergoing transcatheter aortic valve implantation (TAVI) are sparse. The aim of the study was to analyze granular details, treatment, and outcomes of patients undergoing TAVI with obstructive, stable CAD from real-world practice. Methods : REVASC-TAVI (Management of myocardial REVASCularization in patients undergoing Transcatheter Aortic Valve Implantation with coronary artery disease) is an investigator-initiated, multicenter registry, which collected data from patients undergoing TAVI with obstructive stable CAD found during the pre-TAVI work-up. Results : A total of 2025 patients from 30 centers worldwide with complete follow-up were included in the registry. Most patients had single-vessel CAD (56.1%). An involvement of proximal coronary tracts was detected in 62.5% of cases, with 12.0% of patients having CAD in left main (LM). Most patients received percutaneous coronary intervention (PCI) (n = 1617, 79.9%), especially those with proximal CAD (90.4%). At 2 years, the rates of all-cause death [Kaplan-Meier (KM) estimates 20.1% vs. 18.8%, p
log-rank = 0.86] and of the composite of all-cause death, stroke, myocardial infarction, and rehospitalization for heart failure (KM estimates 29.7% vs. 27.5%, plog-rank = 0.82) did not differ between patients undergoing PCI and those who were not. Conclusions : Patients undergoing TAVI with obstructive CAD more commonly had a single-vessel disease and an involvement of proximal coronary tracts. They were commonly treated with PCI, with similar outcomes compared to those treated conservatively., Competing Interests: Thomas Pilgrim received research grants to the institution from Biotronik, Boston Scientific, and Edwards Lifesciences; and speaker/consultancy fees from Medtronic, Boston Scientific, Biotronik, and HighLifeSAS. Ole De Backer received institutional research grants and/or consulting fees from Abbott and Boston Scientific. Lars Sondergaard received consultant fees and/or institutional research grants from Abbott, Boston Scientific, Medtronic, and SMT. Maurizio Taramasso is a consultant for Abbott, Edwards Lifesciences, Boston Scientific, Shenqi Medical, CoreMedic, MEDIRA, 4tech, Simulands, Occlufit, and MTEX. Corrado Tamburino is a consultant for Medtronic. All other authors have nothing to disclose.- Published
- 2024
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25. Comparison between Imaging and Physiology in Guiding Coronary Revascularization: A Meta-Analysis.
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Improta R, Di Pietro G, Giansanti M, Bruno F, De Filippo O, Tocci M, Colantonio R, Sardella G, D'Ascenzo F, and Mancone M
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Background : Percutaneous coronary intervention (PCI) is a widely used revascularization strategy for coronary artery disease. The choice between imaging-guided and physiology-guided PCI has been a subject of debate. This meta-analysis aims to systematically compare outcomes between imaging and physiology-guided PCI and management of intermediate coronary lesions (ICLs). Methods : A comprehensive literature search was conducted across major databases for studies published up to December 2023 following PRISMA guidelines. Seven eligible studies comparing imaging-guided and physiology-guided PCI were selected for the final analysis. Relevant outcome measures included major adverse cardiovascular events (MACE), target vessel revascularization (TVR), target vessel failure (TVF), and target lesion revascularization (TLR). Subgroup analysis was performed for ICLs. Results : A total of 5701 patients were included in the meta-analysis. After a mean follow-up of 2.1 years, imaging-guided PCI was associated with lower rates of TVR compared to physiology-guided PCI (OR 0.70, 95% CI 0.52-0.95, p = 0.02); concerning MACE, TVF, and TLR, no differences were found. When the analysis was restricted to studies considering ICLs management, there were no differences between the two techniques. Meta regression analysis did not show any impact of acute coronary syndromes (ACS) presentation on MACE and TVR. Conclusions : The findings suggest that imaging-guided PCI may reduce the need for future revascularization of the target vessel compared to the functional-guided approach, and this result was not influenced by ACS presentation. These results may have important implications for clinical practice, guiding interventional cardiologists in selecting the most appropriate guidance strategy.
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- 2024
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26. A Meta-Analysis of Short-Term Outcomes of TAVR versus SAVR in Bicuspid Aortic Valve Stenosis and TAVR Results in Different Bicuspid Valve Anatomies.
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Improta R, Di Pietro G, Kola N, Birtolo LI, Colantonio R, Bruno E, Tocci M, Giansante A, Sannino M, Zullino V, Monosilio S, Cimino S, Maestrini V, Severino P, Badagliacca R, Lavalle C, Celli P, Saade W, Musto C, D'Ascenzo F, Miraldi F, Vizza CD, Sardella G, and Mancone M
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Background: To provide a comprehensive analysis of the current literature comparing the outcomes of surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic stenosis (BAS), with particular attention to BAV morphology in patients undergoing TAVR., Methods: Following PRISMA guidelines, all relevant articles with no design restrictions from PubMed, CCTR (Cochrane Controlled Trials Register), and Google Scholar were screened for inclusion. Studies were included if they reported clinical endpoints for SAVR and TAVR or, in BAS treated with TAVR, for type 1 and non-type 1 morphology. Odds ratio and Cohen's D were considered as effect size measurements for qualitative and quantitative variables, respectively., Results: A total of eight studies comparing short-term outcomes between SAVR and TAVR and nine studies with outcomes data between type 1 and non-type 1 BAS treated with TAVR were considered for the final analysis. No statistically significant difference was found for what concerns the rates of death, stroke, and acute kidney injury between SAVR and TAVR. In comparison to patients undergoing SAVR, the incidence of PPI (permanent pacemaker implantation) was greater in the TAVR group (OR 0.35, 95% CI 0.15-0.79, p = 0.01), and the frequency of bleeding events was found to be higher among patients undergoing SAVR (OR 4.3, 95% CI 2.9-6.4, p < 0.001). The probabilities of 30-day mortality, stroke, and any bleeding were not significantly affected by bicuspid valve morphology in TAVR patients. PPI or development of new conduction anomalies was found to be more frequent in type 1 anatomies (OR 0.46, 95% CI 0.30-0.70, p <0.001). Mildly lower post-procedural transprothesic gradients were found in patients with type 1 morphology., Conclusions: In BAS patients, TAVR has comparable short-term outcomes rates with SAVR, but higher PPI rates and lower incidence of bleeding events. In patients undergoing TAVR, type 1 BAS is associated with lower postoperative transvalvular gradients but higher PPI rates and conduction abnormalities.
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- 2023
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27. Comparison of different percutaneous revascularisation timing strategies in patients undergoing transcatheter aortic valve implantation.
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Rheude T, Costa G, Ribichini FL, Pilgrim T, Amat Santos IJ, De Backer O, Kim WK, Ribeiro HB, Saia F, Bunc M, Tchétché D, Garot P, Mylotte D, Burzotta F, Watanabe Y, Bedogni F, Tesorio T, Tocci M, Franzone A, Valvo R, Savontaus M, Wienemann H, Porto I, Gandolfo C, Iadanza A, Bortone AS, Mach M, Latib A, Biasco L, Taramasso M, Zimarino M, Tomii D, Nuyens P, Sondergaard L, Camara SF, Palmerini T, Orzalkiewicz M, Steblovnik K, Degrelle B, Gautier A, Del Sole PA, Mainardi A, Pighi M, Lunardi M, Kawashima H, Criscione E, Cesario V, Biancari F, Zanin F, Esposito G, Adam M, Grube E, Baldus S, De Marzo V, Piredda E, Cannata S, Iacovelli F, Andreas M, Frittitta V, Dipietro E, Reddavid C, Strazzieri O, Motta S, Angellotti D, Sgroi C, Xhepa E, Kargoli F, Tamburino C, Joner M, and Barbanti M
- Subjects
- Humans, Treatment Outcome, Aortic Valve surgery, Risk Factors, Transcatheter Aortic Valve Replacement, Coronary Artery Disease surgery, Coronary Artery Disease complications, Percutaneous Coronary Intervention methods, Aortic Valve Stenosis therapy, Myocardial Infarction complications
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Background: The optimal timing to perform percutaneous coronary interventions (PCI) in transcatheter aortic valve implantation (TAVI) patients remains unknown., Aims: We sought to compare different PCI timing strategies in TAVI patients., Methods: The REVASC-TAVI registry is an international registry including patients undergoing TAVI with significant, stable coronary artery disease (CAD) at preprocedural workup. In this analysis, patients scheduled to undergo PCI before, after or concomitantly with TAVI were included. The main endpoints were all-cause death and a composite of all-cause death, stroke, myocardial infarction (MI) or rehospitalisation for congestive heart failure (CHF) at 2 years. Outcomes were adjusted using the inverse probability treatment weighting (IPTW) method., Results: A total of 1,603 patients were included. PCI was performed before, after or concomitantly with TAVI in 65.6% (n=1,052), 9.8% (n=157) or 24.6% (n=394), respectively. At 2 years, all-cause death was significantly lower in patients undergoing PCI after TAVI as compared with PCI before or concomitantly with TAVI (6.8% vs 20.1% vs 20.6%; p<0.001). Likewise, the composite endpoint was significantly lower in patients undergoing PCI after TAVI as compared with PCI before or concomitantly with TAVI (17.4% vs 30.4% vs 30.0%; p=0.003). Results were confirmed at landmark analyses considering events from 0 to 30 days and from 31 to 720 days., Conclusions: In patients with severe aortic stenosis and stable coronary artery disease scheduled for TAVI, performance of PCI after TAVI seems to be associated with improved 2-year clinical outcomes compared with other revascularisation timing strategies. These results need to be confirmed in randomised clinical trials.
- Published
- 2023
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28. Management of Myocardial Revascularization in Patients With Stable Coronary Artery Disease Undergoing Transcatheter Aortic Valve Implantation.
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Costa G, Pilgrim T, Amat Santos IJ, De Backer O, Kim WK, Barbosa Ribeiro H, Saia F, Bunc M, Tchetche D, Garot P, Ribichini FL, Mylotte D, Burzotta F, Watanabe Y, De Marco F, Tesorio T, Rheude T, Tocci M, Franzone A, Valvo R, Savontaus M, Wienemann H, Porto I, Gandolfo C, Iadanza A, Bortone AS, Mach M, Latib A, Biasco L, Taramasso M, Zimarino M, Tomii D, Nuyens P, Sondergaard L, Camara SF, Palmerini T, Orzalkiewicz M, Steblovnik K, Degrelle B, Gautier A, Del Sole PA, Mainardi A, Pighi M, Lunardi M, Kawashima H, Criscione E, Cesario V, Biancari F, Zanin F, Joner M, Esposito G, Adam M, Grube E, Baldus S, De Marzo V, Piredda E, Cannata S, Iacovelli F, Andreas M, Frittitta V, Dipietro E, Reddavid C, Strazzieri O, Motta S, Angellotti D, Sgroi C, Kargoli F, Tamburino C, and Barbanti M
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- Humans, Stroke Volume, Risk Factors, Treatment Outcome, Ventricular Function, Left, Myocardial Revascularization adverse effects, Aortic Valve diagnostic imaging, Aortic Valve surgery, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease therapy, Coronary Artery Disease complications, Transcatheter Aortic Valve Replacement adverse effects, Aortic Valve Stenosis diagnostic imaging, Aortic Valve Stenosis surgery, Aortic Valve Stenosis complications, Myocardial Infarction complications, Stroke etiology, Stroke surgery, Percutaneous Coronary Intervention adverse effects
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Background: The best management of stable coronary artery disease (CAD) in patients undergoing transcatheter aortic valve implantation (TAVI) is still unclear due to the marked inconsistency of the available evidence., Methods: The REVASC-TAVI registry (Management of Myocardial Revascularization in Patients Undergoing Transcatheter Aortic Valve Implantation With Coronary Artery Disease) collected data from 30 centers worldwide on patients undergoing TAVI who had significant, stable CAD at preprocedural work-up. For the purposes of this analysis, patients with either complete or incomplete myocardial revascularization were compared in a propensity score matched analysis, to take into account of baseline confounders. The primary and co-primary outcomes were all-cause death and the composite of all-cause death, stroke, myocardial infarction, and rehospitalization for heart failure, respectively, at 2 years., Results: Among 2407 patients enrolled, 675 pairs of patients achieving complete or incomplete myocardial revascularization were matched. The primary (21.6% versus 18.2%, hazard ratio' 0.88 [95% CI, 0.66-1.18]; P =0.38) and co-primary composite (29.0% versus 27.1%, hazard ratio' 0.97 [95% CI, 0.76-1.24]; P =0.83) outcome did not differ between patients achieving complete or incomplete myocardial revascularization, respectively. These results were consistent across different prespecified subgroups of patients (< or >75 years of age, Society of Thoracic Surgeons score > or <4%, angina at baseline, diabetes, left ventricular ejection fraction > or <40%, New York Heart Association class I/II or III/IV, renal failure, proximal CAD, multivessel CAD, and left main/proximal anterior descending artery CAD; all P values for interaction >0.10)., Conclusions: The present analysis of the REVASC-TAVI registry showed that, among TAVI patients with significant stable CAD found during the TAVI work-up, completeness of myocardial revascularization achieved either staged or concomitantly with TAVI was similar to a strategy of incomplete revascularization in reducing the risk of all cause death, as well as the risk of death, stroke, myocardial infarction, and rehospitalization for heart failure at 2 years, regardless of the clinical and anatomical situations.
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- 2022
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29. Prognostic value of systemic inflammatory response syndrome after transcatheter aortic valve implantation.
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Monosilio S, Filomena D, Cimino S, Birtolo LI, Tocci M, Mancone M, Sardella G, Fedele F, Maestrini V, and Agati L
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- Humans, Prognosis, Retrospective Studies, Systemic Inflammatory Response Syndrome diagnosis, Systemic Inflammatory Response Syndrome epidemiology, Systemic Inflammatory Response Syndrome etiology, Aortic Valve Stenosis diagnostic imaging, Aortic Valve Stenosis surgery, Hypertension, Pulmonary etiology, Transcatheter Aortic Valve Replacement
- Abstract
Aims: Systemic inflammatory response syndrome (SIRS) could affect mortality after transcatheter aortic valve implantation (TAVI) up to 12 months of follow-up. The aim of this study was to evaluate the prevalence of SIRS after TAVI and its impact on all-cause mortality up to 24 months follow-up., Methods: We retrospectively enrolled 132 patients with symptomatic severe aortic stenosis undergoing TAVI. SIRS development during the first 72 h after the intervention was evaluated. Other postoperative complications were defined according to the Valve Academic Research Consortium 2 (VARC2). All patients underwent follow-up at 30 days and 24 months. Endpoints were 30-days and 24-months mortality., Results: Post-TAVI SIRS developed in 27 patients (20%). At 30-day follow-up, all-cause death occurred in 10 (8%) patients and SIRS occurred more frequently in patients with adverse short-term outcome (60 vs. 17%; P = 0.001). Twenty-four months all-cause death occurred in 25 (19%) patients. SIRS resulted as an independent predictor of long-term outcome [hazard ratio 3.7; 95% confidence interval (95% CI) 1.5-9; P = 0.004], along with major vascular complications (hazard ratio 4; 95% CI 1.6-9.9; P = 0.003), relevant bleedings (hazard ratio 6.4; 95% CI 1.5-28; P = 0.013) and baseline pulmonary hypertension (hazard ratio 2.4; 95% CI 1.05-5.6; P = 0.039)., Conclusion: Postoperative SIRS was more frequent in patients who died at 30 days follow-up. Moreover, SIRS resulted as a predictor of 24-month mortality along with vascular complications, relevant bleedings and baseline pulmonary hypertension., (Copyright © 2022 Italian Federation of Cardiology - I.F.C. All rights reserved.)
- Published
- 2022
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30. A review of sexual transmitted infection rates among sexually assaulted patients that present for care.
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Scannell-Tocci M and Reynolds R
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- Adult, Cross-Sectional Studies, Humans, Retrospective Studies, Sexual Behavior, Crime Victims, HIV Infections epidemiology, Sexually Transmitted Diseases epidemiology
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Background: Patients who experience sexual assault are at risk of adverse health outcomes including sexually transmitted infections (STI) and often present to various healthcare centers for post-assault care. Unfortunately, there are no standard guidelines on testing for STI among this patient population. Having an understanding of prevalence rates is essential and will help guide protocols, care guidelines and STI testing. In efforts to have a better understanding a review was conducted of published studies examining prevalence rates of STI among sexually assaulted patients., Methods: This paper is a review of published studies over the last 10 years that have examined prevalence of STIs including HIV among adult patients who have presented to care after a sexual assault., Results: A total of 12 studies that were included in this review. Studies used were, observational, retrospective descriptive, cross sectional and longitudinal studies. Years of data collection of the studies from 2001-2019., Conclusions: This review notes a wide range of rates of STI among victims of sexual assault and wide variation in the types of STI that were tested and the percentage of patients tested at the different healthcare settings with some testing 100% of victims and other testing 22% of victims. Future research and healthcare recommendations point to a need for a more standardized approach to testing sexually assaulted patients and type of STI being tested., (Copyright © 2022 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)
- Published
- 2022
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31. Prediction of Microstructure for AISI316L Steel from Numerical Simulation of Laser Powder Bed Fusion.
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Abrami MB, Tocci M, Obeidi MA, Brabazon D, and Pola A
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Abstract: Laser powder bed fusion (L-PBF) success in the industrial scenario strongly depends on the ability to manufacture components without defects and with high building rates, but also on the ability to effectively control the microstructure to gain the required properties in the final component. In this regard, the recently developed numerical simulation software of L-PBF technologies can represent an effective tool, since many of them provide solidification data (i.e. temperature gradient and cooling rate) useful for microstructure prediction. In this work, a numerical model was applied to simulate the processing of four single scan tracks of 316L stainless steel processed with different parameters. Temperature and cooling rate around the melt pool were extracted from the numerical model and used to estimate the microstructure cellular arm spacing and the microhardness. Experimental measurements were then compared with the estimated values revealing good agreement. The good agreement between experimental and estimated values shows the advantages of the proposed method for microstructure and microhardness prediction based on numerical modelling as a useful resource for process optimization according to the required final microstructural features., Competing Interests: Conflict of interestThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© The Author(s) 2022, corrected publication 2022.)
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- 2022
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32. Arrhythmic safety of hydroxychloroquine in COVID-19 patients from different clinical settings.
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Gasperetti A, Biffi M, Duru F, Schiavone M, Ziacchi M, Mitacchione G, Lavalle C, Saguner A, Lanfranchi A, Casalini G, Tocci M, Fabbricatore D, Salghetti F, Mariani MV, Busana M, Bellia A, Cogliati CB, Viale P, Antinori S, Galli M, Galiè N, Tondo C, and Forleo GB
- Subjects
- Arrhythmias, Cardiac chemically induced, COVID-19 epidemiology, Female, Humans, Hydroxychloroquine adverse effects, Italy epidemiology, Male, Middle Aged, SARS-CoV-2, Arrhythmias, Cardiac virology, Electrocardiography, Hydroxychloroquine administration & dosage, COVID-19 Drug Treatment
- Abstract
Aims: The aim of the study was to describe ECG modifications and arrhythmic events in COVID-19 patients undergoing hydroxychloroquine (HCQ) therapy in different clinical settings., Methods and Results: COVID-19 patients at seven institutions receiving HCQ therapy from whom a baseline and at least one ECG at 48+ h were available were enrolled in the study. QT/QTc prolongation, QT-associated and QT-independent arrhythmic events, arrhythmic mortality, and overall mortality during HCQ therapy were assessed. A total of 649 COVID-19 patients (61.9 ± 18.7 years, 46.1% males) were enrolled. HCQ therapy was administrated as a home therapy regimen in 126 (19.4%) patients, and as an in-hospital-treatment to 495 (76.3%) hospitalized and 28 (4.3%) intensive care unit (ICU) patients. At 36-72 and at 96+ h after the first HCQ dose, 358 and 404 ECGs were obtained, respectively. A significant QT/QTc interval prolongation was observed (P < 0.001), but the magnitude of the increase was modest [+13 (9-16) ms]. Baseline QT/QTc length and presence of fever (P = 0.001) at admission represented the most important determinants of QT/QTc prolongation. No arrhythmic-related deaths were reported. The overall major ventricular arrhythmia rate was low (1.1%), with all events found not to be related to QT or HCQ therapy at a centralized event evaluation. No differences in QT/QTc prolongation and QT-related arrhythmias were observed across different clinical settings, with non-QT-related arrhythmias being more common in the intensive care setting., Conclusion: HCQ administration is safe for a short-term treatment for patients with COVID-19 infection regardless of the clinical setting of delivery, causing only modest QTc prolongation and no directly attributable arrhythmic deaths., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)
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- 2020
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33. Coronavirus disease 2019 in Rome: was it circulating before December?
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Birtolo LI, Maestrini V, Severino P, Chimenti C, Agnes G, Tocci M, Colaiacomo MC, Francone M, Mancone M, and Fedele F
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- Betacoronavirus, COVID-19, Humans, Italy epidemiology, SARS-CoV-2, Tomography, X-Ray Computed methods, Tomography, X-Ray Computed statistics & numerical data, Coronavirus Infections diagnosis, Coronavirus Infections epidemiology, Coronavirus Infections physiopathology, Coronavirus Infections therapy, Hospitalization statistics & numerical data, Medical Records, Problem-Oriented statistics & numerical data, Pandemics statistics & numerical data, Pneumonia, Viral diagnosis, Pneumonia, Viral diagnostic imaging, Pneumonia, Viral epidemiology, Pneumonia, Viral etiology, Pneumonia, Viral physiopathology, Pneumonia, Viral therapy
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- 2020
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34. Home care for heart failure: can caregiver education prevent hospital admissions? A randomized trial in primary care.
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Padula MS, D'Ambrosio GG, Tocci M, D'Amico R, Banchelli F, Angeli L, Scarpa M, Capelli O, Cricelli C, and Boriani G
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- Aged, Aged, 80 and over, Caregivers psychology, Disease Progression, Feasibility Studies, Female, Heart Failure diagnosis, Heart Failure physiopathology, Humans, Italy, Male, Risk Factors, Time Factors, Treatment Outcome, Caregivers education, Health Education methods, Health Knowledge, Attitudes, Practice, Heart Failure therapy, Home Care Services, Patient Admission, Primary Health Care methods
- Abstract
Aim: To assess the feasibility and effectiveness of a low-complexity, low-cost model of caregiver education in primary care, targeted to reduce hospitalizations of heart failure patients., Methods: A cluster-randomized, controlled, open trial was proposed to general practitioners, who were invited to identify patients with heart failure, exclusively managed at home and continuously attended by a caregiver. Participating general practitioners were then randomized to: usual treatment; caregiver education (educational session for recognizing early symptoms/signs of heart failure, with recording in a diary of a series of patient parameters, including body weight, blood pressure, heart rate). The patients were observed at baseline and during a 12-month follow-up., Results: Three hundred and thirteen patients were enrolled (163 in the intervention, 150 in the usual care group), 63% women, mean age 85.3 ± 7.7 years. At the end of the 12-month follow-up, a trend towards a lower incidence of hospitalizations was observed in the intervention group (hazard ratio 0.73; 95% CI 0.53-1.01 P = 0.061). Subgroup analysis showed that for patients with persistent/permanent atrial fibrillation, age less than 90 years or Barthel score equal to or greater than 50 a significant lower hospital admission rate occurred in the intervention group (hazard ratio 0.63; 95% CI 0.39-0.99; P = 0.048, hazard ratio 0.66; 95% CI 0.45-0.97; P = 0.036 and hazard ratio 0.61; 95% CI 0.41-0.89; P = 0.011, respectively)., Conclusion: Caregivers training for early recognition of symptoms/signs of worsening heart failure may be effective in reducing hospitalizations, although the benefit was evident only in specific patient subgroups (with persistent/permanent atrial fibrillation, age <90 years or Barthel score ≥ 50), with only a positive trend in the whole cohort., Trial Registration: ClinicalTrials.gov Identifier: NCT03389841.
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- 2019
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35. Influence of Ultrasound Treatment on Cavitation Erosion Resistance of AlSi7 Alloy.
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Pola A, Montesano L, Tocci M, and La Vecchia GM
- Abstract
Ultrasound treatment of liquid aluminum alloys is known to improve mechanical properties of castings. Aluminum foundry alloys are frequently used for production of parts that undergo severe cavitation erosion phenomena during service. In this paper, the effect of the ultrasound treatment on cavitation erosion resistance of AlSi7 alloy was assessed and compared to that of conventionally cast samples. Cavitation erosion tests were performed according to ASTM G32 standard on as-cast and heat treated castings. The response of the alloy in each condition was investigated by measuring the mass loss as a function of cavitation time and by analyzing the damaged surfaces by means of optical and scanning electron microscope. It was pointed out that the ultrasound treatment increases the cavitation erosion resistance of the alloy, as a consequence of the higher chemical and microstructural homogeneity, the finer grains and primary particles and the refined structure of the eutectic induced by the treatment itself.
- Published
- 2017
- Full Text
- View/download PDF
36. Education protects babies from HIV infection.
- Author
-
Tocci M
- Subjects
- Antiviral Agents therapeutic use, Female, HIV Infections nursing, Humans, Infant, Pregnancy, Pregnancy Complications, Infectious nursing, HIV Infections transmission, Infectious Disease Transmission, Vertical prevention & control, Patient Education as Topic, Pregnancy Complications, Infectious drug therapy
- Published
- 2011
- Full Text
- View/download PDF
37. Effects of the beta3-adrenoceptor (Adrb3) agonist SR58611A (amibegron) on serotonergic and noradrenergic transmission in the rodent: relevance to its antidepressant/anxiolytic-like profile.
- Author
-
Claustre Y, Leonetti M, Santucci V, Bougault I, Desvignes C, Rouquier L, Aubin N, Keane P, Busch S, Chen Y, Palejwala V, Tocci M, Yamdagni P, Didier M, Avenet P, Le Fur G, Oury-Donat F, Scatton B, and Steinberg R
- Subjects
- Action Potentials drug effects, Action Potentials physiology, Adrenergic Uptake Inhibitors pharmacology, Adrenergic beta-2 Receptor Agonists, Analysis of Variance, Animals, Brain anatomy & histology, Brain cytology, Brain metabolism, Dose-Response Relationship, Drug, Drug Administration Routes, Drug Interactions, Fluoxetine pharmacology, Male, Mice, Microdialysis, Morpholines pharmacology, Motor Activity drug effects, Neurons drug effects, Neurons physiology, Rats, Reboxetine, Receptors, Adrenergic, beta-2 genetics, Receptors, Adrenergic, beta-2 metabolism, Selective Serotonin Reuptake Inhibitors pharmacology, Tryptophan metabolism, Adrenergic beta-Agonists pharmacology, Brain drug effects, Norepinephrine metabolism, Serotonin metabolism, Tetrahydronaphthalenes pharmacology
- Abstract
SR58611A is a selective beta(3)-adrenoceptor (Adrb3) agonist which has demonstrated antidepressant and anxiolytic properties in rodents. The present study confirmed the detection of Adrb3 mRNA transcript in rodent brain sub-regions and evaluated the effect of SR58611A on serotonergic and noradrenergic transmission in rats and mice in an attempt to elucidate the mechanism(s) underlying these properties. SR58611A (3 and 10 mg/kg, p.o.) increased the synthesis of 5-HT and tryptophan (Trp) levels in several rodent brain areas (cortex, hippocampus, hypothalamus, striatum). Moreover, SR58611A (10 mg/kg, p.o.) increased the release of 5-HT assessed by in vivo microdialysis in rat prefrontal cortex. Systemic (3 mg/kg, i.v.) or chronic administration of SR58611A (10 mg/kg, p.o.), in contrast to fluoxetine (15 mg/kg, p.o.), did not modify the activity of serotonergic neurons in the rat dorsal raphe nucleus. The increase in 5-HT synthesis induced by SR58611A was not observed in Adrb3s knockout mice, suggesting a selective involvement of Adrb3s in this effect. SR58611A (3 and 10 mg/kg, p.o.) did not modify norepinephrine synthesis and metabolism but increased its release in rat brain. Repeated administration of SR58611A (10 mg/kg, p.o.) did not modify basal norepinephrine release in rat prefrontal cortex whereas it prevented its tail-pinch stress-induced enhancement similarly to reboxetine (15 mg/kg, p.o.). Finally SR58611A increased the firing rate of noradrenergic neurons in the rat locus coeruleus following systemic (3 mg/kg, i.v.) or local (0.01 and 1 microM) but not chronic (10 mg/kg, p.o.) administration. These results suggest that the anxiolytic- and antidepressant-like activities of SR58611A involve an increase of brain serotonergic and noradrenergic neurotransmissions, triggered by activation of Adrb3s.
- Published
- 2008
- Full Text
- View/download PDF
38. Venous and arterial blood lactate in HIV-infected patients.
- Author
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Zala C, Harris M, Ochoa C, Tocci M, Quercia R, Mittelman G, Perez H, Cahn P, and Montaner JS
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Anti-HIV Agents adverse effects, HIV Infections blood, HIV Infections drug therapy, Lactic Acid blood, Stavudine adverse effects
- Published
- 2002
39. The activation state of p38 mitogen-activated protein kinase determines the efficiency of ATP competition for pyridinylimidazole inhibitor binding.
- Author
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Frantz B, Klatt T, Pang M, Parsons J, Rolando A, Williams H, Tocci MJ, O'Keefe SJ, and O'Neill EA
- Subjects
- Binding, Competitive genetics, Calcium-Calmodulin-Dependent Protein Kinases antagonists & inhibitors, Calcium-Calmodulin-Dependent Protein Kinases genetics, Cell Line, Enzyme Activation genetics, Humans, Imidazoles pharmacology, Intracellular Signaling Peptides and Proteins, Kinetics, Phosphorylation drug effects, Protein Binding genetics, Protein Serine-Threonine Kinases antagonists & inhibitors, Pyridines pharmacology, Radioligand Assay, Recombinant Proteins biosynthesis, Recombinant Proteins metabolism, p38 Mitogen-Activated Protein Kinases, Adenosine Triphosphate metabolism, Calcium-Calmodulin-Dependent Protein Kinases metabolism, Imidazoles metabolism, Mitogen-Activated Protein Kinases, Protein Serine-Threonine Kinases metabolism, Pyridines metabolism
- Abstract
The serine/threonine kinase p38 is a ubiquitous, highly conserved, stress responsive, signal-transducing enzyme. It regulates the production of proinflammatory mediators and is the target of the cytokine synthesis inhibitory pyridinylimidazoles. We have expressed human p38 in Drosophila S2 cells and characterized preparations of mixed unphosphorylated/monophosphorylated (inactive) and homogeneously diphosphorylated (active) forms of the enzyme. We observed that only the active preparation of the enzyme has significant kinase activity when assayed using an ATF2-GST fusion protein as the substrate. We determined that the value of KM[ATP] in this reaction is 25 microM and that the pyridinylimidazole inhibitor of p38 kinase activity, SB203580, competes with ATP. We have found that a tritiated pyridinylimidazole, SB202190, has an equal affinity for both the active and inactive forms of the enzyme and that SB203580 competes with it equally well for binding to either form of the enzyme. However, ATP can compete with the tritiated inhibitor for binding to only the active form of the enzyme. Further, we demonstrate in vivo that at concentrations consistent with its IC50 as a cytokine inhibitor, SB203580 can inhibit stimulus-induced phosphorylation of p38 at the Thr-Gly-Tyr activation motif. Our observations suggest that pyridinylimidazoles may block the biological activity of p38 kinase by binding to the inactive form of p38 and reducing its rate of activation. Under these conditions, ATP would not effectively compete with the inhibitors in vivo.
- Published
- 1998
- Full Text
- View/download PDF
40. Structure and function of interleukin-1 beta converting enzyme.
- Author
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Tocci MJ
- Subjects
- Animals, Caspase 1, Cysteine Endopeptidases genetics, Cysteine Endopeptidases isolation & purification, Humans, Interleukin-1 metabolism, Mice, Mice, Knockout, Protease Inhibitors, Substrate Specificity, Cysteine Endopeptidases chemistry, Cysteine Endopeptidases physiology
- Abstract
An overwhelming body of evidence has shown that IL-1 beta is a major mediator of inflammatory disease (Tocci and Schmidt, 1996). The discovery of ICE, a unique processing enzyme involved in the production of active IL-1 beta, has provided a new approach to specifically block the production of this potent cytokine. Consequently, the discovery and development of inhibitors against the enzyme could hold great promise therapeutically. Potent inhibitors of the enzyme would be useful in the treatment of a number of important inflammatory diseases and potentially in the management of leukemia (Arend, 1993b; Estrov and Talpaz, 1996). A number of key questions must be answered before the therapeutic potential of such inhibitors can be realized. The development of a pharmaceutically acceptable cysteine proteinase inhibitor will almost certainly involve new chemical strategies gauged at safely inactivating the enzyme. For such inhibitors, it will be necessary to achieve selectivity for ICE from among the growing number of ICE family members while retaining potency. It will also be important to establish the level of inhibition of IL-1 beta required to achieve therapeutic efficacy. The studies comparing IL-1 beta- and ICE-deficient mice suggest that complete abrogation of IL-1 beta is required to achieve efficacy in models of inflammation. It is not known if this is the case in humans. Understanding the source of the residual IL-1 beta produced in ICE-deficient mice will be important in order to ascertain if a similar mechanism could generate active IL-1 beta in patients receiving if a ICE inhibitor. As for ICE itself, a number of formidable questions remain regarding its regulation and mechanism of activation. Answering these questions experimentally will present a major challenge due to the extremely low levels of enzyme present in cells. Studies on other family members may provide easier access to some of these questions and provide clues that can be applied to ICE. The components of the pathway involved in IL-1 trafficking and secretion are unknown, as are the mechanisms of ICE activation and regulation. Clearly other cellular proteins that have yet to be discovered will be involved in each of these processes, opening up new avenues of research in this field.
- Published
- 1997
- Full Text
- View/download PDF
41. IL-1 beta convertase (ICE) does not play a requisite role in apoptosis induced in T lymphoblasts by Fas-dependent or Fas-independent CTL effector mechanisms.
- Author
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Smith DJ, McGuire MJ, Tocci MJ, and Thiele DL
- Subjects
- Animals, Caspase 1, Caspase 3, Cysteine Endopeptidases deficiency, Cysteine Proteinase Inhibitors pharmacology, Cytotoxicity, Immunologic drug effects, Enzyme Precursors pharmacology, Hematopoietic Stem Cells drug effects, Membrane Glycoproteins pharmacology, Mice, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Inbred CBA, Mice, Knockout, Oligopeptides pharmacology, Perforin, Pore Forming Cytotoxic Proteins, T-Lymphocytes drug effects, Apoptosis immunology, Caspases, Cysteine Endopeptidases pharmacology, Hematopoietic Stem Cells immunology, T-Lymphocytes, Cytotoxic immunology, fas Receptor pharmacology
- Abstract
Both IL-1beta convertase (ICE) and other members of the ICE-like family of proteases have been reported to play a role in Fas-mediated apoptosis. Con A-stimulated T lymphoblasts generated from splenocytes isolated from ICE-deficient H-2b mice were found to be more susceptible than wild-type lymphoblasts to DNA fragmentation induced by H-2b-specific CTL derived from normal or Fas ligand-deficient gld/gld mice. Trinitrophenyl (TNP)-modified, H-2b target cell-specific CTL were generated from perforin-deficient mice and were found to induce DNA fragmentation only in target cells expressing functional Fas receptors. Similar rates of DNA fragmentation were induced in TNP-modified ICE -/- and ICE +/+ T lymphoblast targets by perforin -/- TNP-modified, H-2b target cell-specific CTL. In addition, anti-Fas Abs induced apoptosis in thymocytes, Con A-stimulated spleen T cells, LPS-stimulated spleen B cells, and thymocytes from ICE -/- mice. However, DNA fragmentation induced by either allospecific FasL-defective CTL, or by perforin-deficient, TNP-modified, H-2b target cell-specific CTL was prevented in ICE -/- target cells loaded by electroporation with Ac-DEVD-CHO, an inhibitor of CPP32 and related ICE family proteases. These findings indicate that ICE does not play a requisite role in Fas-dependent or Fas-independent mechanisms of apoptosis induced in peripheral T lymphoblasts by CTL. However, both major pathways of CTL-induced apoptosis appear to be dependent on the enzymatic activity of other ICE family proteases.
- Published
- 1997
42. Expression and immunoaffinity purification of human inducible nitric-oxide synthase. Inhibition studies with 2-amino-5,6-dihydro-4H-1,3-thiazine.
- Author
-
Calaycay JR, Kelly TM, MacNaul KL, McCauley ED, Qi H, Grant SK, Griffin PR, Klatt T, Raju SM, Nussler AK, Shah S, Weidner JR, Williams HR, Wolfe GC, Geller DA, Billiar TR, MacCoss M, Mumford RA, Tocci MJ, Schmidt JA, Wong KK, and Hutchinson NI
- Subjects
- Chromatography, High Pressure Liquid, Enzyme Induction, Humans, Kinetics, NADP metabolism, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Nitric Oxide Synthase metabolism, Radiation-Protective Agents pharmacology, Thiazines pharmacology
- Abstract
Recombinant human inducible nitric-oxide synthase (rH-iNOS) was expressed in the baculovirus system and purified by a novel immunoaffinity column. rH-iNOS and its native counterpart from cytokine-stimulated primary hepatocytes exhibited similar molecular mass of 130 kDa on SDS-polyacrylamide gel electrophoresis, recognition by antipeptide antibodies, specific activities, and IC50 values for inhibitors. The active dimeric form exhibited a specific activity range of 114-260 nmol/min/mg at 37 degrees C and contained 1.15 +/- 0.04 mol of calmodulin/monomer. The enzyme exhibited a Soret lambdamax at 396 nm with a shoulder at 460 nm and contained 0. 28-0.64 mol of heme/monomer. Dithionite reduction under CO yielded an absorbance maximum at 446 nm, indicating a P450-type heme. Imidazole induced a type II difference spectrum, reversible by L-Arg. 2-Amino-5,6-dihydro-4H-1,3-thiazine (ADT) was competitive versus L-Arg (Ki = 22.6 +/- 1.9 nM), reversed the type II difference spectrum induced by imidazole (Kd = 17.7 nM), and altered the CO-ferrous absorbance of rH-iNOS. L-Arg did not perturb the CO-ferrous adduct directly, but it partially reversed the ADT-induced absorbance shift, indicating that both bind similarly to the protein but interact differently with the heme.
- Published
- 1996
- Full Text
- View/download PDF
43. Regulation of IkB alpha phosphorylation by PKC- and Ca(2+)-dependent signal transduction pathways.
- Author
-
Steffan NM, Bren GD, Frantz B, Tocci MJ, O'Neill EA, and Paya CV
- Subjects
- Animals, Calcineurin, Calmodulin-Binding Proteins metabolism, Cell Line, Fibroblasts metabolism, Humans, NF-KappaB Inhibitor alpha, Phosphoprotein Phosphatases metabolism, Phosphorylation, Calcium metabolism, DNA-Binding Proteins metabolism, I-kappa B Proteins, NF-kappa B metabolism, Protein Kinase C metabolism, Signal Transduction, T-Lymphocytes metabolism
- Abstract
The Ca(2+)-dependent phosphatase calcineurin, a target of FK506 and CsA, synergizes with PKC-induced activation of nuclear factor (NF)-kappa B in T cell lines. We have investigated whether this synergy is present in other cell types and the mechanism(s) by which these two pathways lead to NF-kappa B activation. While this synergy is present in other cell types, in the monocytic cell line U937 calcineurin is also sufficient to activate NF-kappa B. Having previously shown that Ca(2+)- and PKC-dependent pathways synergize by accelerating the degradation of IkB alpha, we focused on the regulation of IkB alpha phosphorylation. While PKC-dependent pathways sequentially result in the phosphorylation and in an incomplete degradation of IkB alpha in T cell lines, co-activation of Ca(2+)-dependent pathways accelerates the rate of IkB alpha phosphorylation and results in its complete degradation. Activation of Ca(2+)-dependent pathways alone do not result in the phosphorylation and/or degradation of IkB alpha in Jurkat T or in U937 cells. Treatment of T cells with the selective PKC inhibitor GF109203X abrogates the PMA-induced IkB alpha phosphorylation/degradation irrespective of activation of Ca(2+)-dependent pathways, but not the phosphorylation and degradation of IkB alpha induced by TNF-alpha, a PKC-independent stimulus. Contrary to the interaction with PKC, Ca(2+)-dependent pathways synergize with TNF-alpha not at the level of IkB alpha phosphorylation, but at the level of its degradation. These results indicate that Ca(2+)-dependent pathways, including the phosphatase calcineurin, participate in the regulation of NF-kappa B in a cell specific fashion and synergize with PKC-dependent and -independent pathways at the level of IkB alpha phosphorylation and degradation.
- Published
- 1995
44. Human IL-1 beta processing and secretion in recombinant baculovirus-infected Sf9 cells is blocked by the cowpox virus serpin crmA.
- Author
-
Howard AD, Palyha OC, Griffin PR, Peterson EP, Lenny AB, Ding GJ, Pickup DJ, Thornberry NA, Schmidt JA, and Tocci MJ
- Subjects
- Amino Acid Sequence, Animals, Baculoviridae genetics, Binding Sites genetics, Caspase 1, Cell Line, Cowpox virus genetics, Cysteine Endopeptidases genetics, Cysteine Endopeptidases metabolism, Humans, In Vitro Techniques, Kinetics, Molecular Sequence Data, Oligopeptides genetics, Protein Processing, Post-Translational drug effects, Recombinant Proteins genetics, Recombinant Proteins metabolism, Serpins genetics, Spodoptera, Substrate Specificity, Interleukin-1 metabolism, Serpins pharmacology, Viral Proteins
- Abstract
Biologically active, mature IL-1 beta (mIL-1 beta) is released from activated monocytes after proteolytic processing from an inactive precursor (pIL-1 beta). IL-1 beta converting enzyme (ICE), the first member of a newly discovered family of cysteine proteinases, is required for this processing event. The cleaved cytokine is released from monocytes by an unknown mechanism which does not employ a standard hydrophobic signal sequence. As in mammalian fibroblasts, insect Sf9 cells do not normally process or secrete human IL-1 beta. The expression of active ICE enables Sf9 cells to process 31-kDa pIL-1 beta correctly at Asp27 and Asp116, and to export 17.5-kDa mIL-1 beta. The recombinant heterodimeric human enzyme purified from Sf9 cells possesses a sp. act. of 2.9 +/- 0.5 x 10(6) U/mg and is indistinguishable from native ICE with regard to its subunit composition and catalytic properties. In this system, co-expression of the cowpox virus crmA gene, an extremely potent serpin inhibitor of ICE (Ki < 7 pM), inhibits ICE activation completely and blocks pIL-1 beta processing and mIL-1 beta secretion by approximately 95%. The results indicate that ICE, in addition to its processing function, facilitates the transport of IL-1 beta across the plasma membrane.
- Published
- 1995
45. Calcineurin acts in synergy with PMA to inactivate I kappa B/MAD3, an inhibitor of NF-kappa B.
- Author
-
Frantz B, Nordby EC, Bren G, Steffan N, Paya CV, Kincaid RL, Tocci MJ, O'Keefe SJ, and O'Neill EA
- Subjects
- Base Sequence, Calcineurin, Cells, Cultured, DNA metabolism, Drug Synergism, Humans, Molecular Sequence Data, NF-KappaB Inhibitor alpha, Oligodeoxyribonucleotides, T-Lymphocytes drug effects, T-Lymphocytes metabolism, Transcription Factor RelB, Transcription Factors antagonists & inhibitors, Calmodulin-Binding Proteins pharmacology, DNA-Binding Proteins antagonists & inhibitors, I-kappa B Proteins, NF-kappa B antagonists & inhibitors, Phosphoprotein Phosphatases pharmacology, Proto-Oncogene Proteins antagonists & inhibitors, Tetradecanoylphorbol Acetate pharmacology
- Abstract
The interleukin-2 (IL-2) promoter consists of several independent T cell receptor (TcR) responsive elements. The induction of promoters dependent on these elements is inhibitable by the immunosuppressants cyclosporin A (CsA) and tacrolimus (FK-506). Calcineurin, a Ca2+/calmodulin-dependent protein phosphatase, is the FK-506- and CsA-sensitive enzyme required for TcR mediated activation of the IL-2 promoter. We report that a constitutively active form of calcineurin partially substitutes for the Ca2+ co-stimulus required to activate the IL-2 promoter elements IL-2A (which binds the factors OAP and Oct-1) and IL-2E (which binds NF-AT), and completely substitutes for the Ca2+ co-stimulus required to stimulate an NF-kappa B-dependent element. Calcineurin stimulates the NF-kappa B element by enhancing inactivation of I kappa B/MAD3, an inhibitor of NF-kappa B, thereby increasing the amount of nuclear NF-kappa B DNA binding activity. These data provide the first demonstration in vivo that activation of a protein phosphatase can inactivate I kappa B, and suggest one possible explanation for mechanism-based toxicities associated with FK-506 and CsA by demonstrating that these drugs can inhibit the calcineurin-dependent activation of a virtually ubiquitous transcription factor.
- Published
- 1994
- Full Text
- View/download PDF
46. FK-506- and CsA-sensitive activation of the interleukin-2 promoter by calcineurin.
- Author
-
O'Keefe SJ, Tamura J, Kincaid RL, Tocci MJ, and O'Neill EA
- Subjects
- Animals, Calcineurin, Calmodulin-Binding Proteins genetics, Cell Line, Chloramphenicol O-Acetyltransferase genetics, Chloramphenicol O-Acetyltransferase metabolism, Chromosome Deletion, Gene Expression Regulation drug effects, Humans, Ionomycin pharmacology, Kinetics, Macromolecular Substances, Mice, Phosphoprotein Phosphatases genetics, Polymerase Chain Reaction, Recombinant Proteins metabolism, Tetradecanoylphorbol Acetate pharmacology, Transcription, Genetic drug effects, Transfection, Calmodulin-Binding Proteins metabolism, Cyclosporine pharmacology, Interleukin-2 genetics, Phosphoprotein Phosphatases metabolism, Promoter Regions, Genetic drug effects, Tacrolimus pharmacology
- Abstract
Antigen recognition by the T-cell receptor (TCR) initiates events including lymphokine gene transcription, particularly interleukin-2, that lead to T-cell activation. The immunosuppressive drugs, cyclosporin A (CsA) and FK-506, prevent T-cell proliferation by inhibiting a Ca(2+)-dependent event required for induction of interleukin-2 transcription. Complexes of FK-506 or CsA and their respective intracellular binding proteins inhibit the calmodulin-dependent protein phosphatase, calcineurin, in vitro. The pharmacological relevance of this observation to immunosuppression or drug toxicity is undetermined. Calcineurin, although present in lymphocytes, has not been implicated in TCR-mediated activation of lymphokine genes or in transcriptional regulation in general. Here we report that transfection of a calcineurin catalytic subunit increases the 50% inhibitory concentration (IC50) of the immunosuppressants FK-506 and CsA, and that a mutant subunit acts in synergy with phorbol ester alone to activate the interleukin-2 promoter in a drug-sensitive manner. These results implicate calcineurin as a component of the TCR signal transduction pathway by demonstrating its role in the drug-sensitive activation of the interleukin-2 promoter.
- Published
- 1992
- Full Text
- View/download PDF
47. Differential effects of IL-1 and TNF alpha on the expression of stromelysin, collagenase and their natural inhibitor, TIMP, in rheumatoid human synovial fibroblasts.
- Author
-
MacNaul KL, Chartrain N, Lark M, Tocci MJ, and Hutchinson NI
- Subjects
- Cells, Cultured, Enzyme Induction drug effects, Fibroblasts metabolism, Gene Expression Regulation drug effects, Humans, Matrix Metalloproteinase 3, Recombinant Proteins pharmacology, Tetradecanoylphorbol Acetate pharmacology, Tissue Inhibitor of Metalloproteinases, Arthritis, Rheumatoid pathology, Collagenases biosynthesis, Fibroblasts drug effects, Glycoproteins biosynthesis, Interleukin-1 pharmacology, Metalloendopeptidases biosynthesis, Synovial Fluid cytology, Tumor Necrosis Factor-alpha pharmacology
- Published
- 1992
48. The FK 506-sensitive nature of the interleukin-2 promoter is derived from a specific array of multiple regulatory elements.
- Author
-
O'Neill EA, Frantz B, Nordby EC, and Tocci MJ
- Subjects
- Base Sequence, Humans, Molecular Sequence Data, Mutagenesis, Site-Directed, Transcription, Genetic drug effects, Interleukin-2 genetics, Promoter Regions, Genetic drug effects, Regulatory Sequences, Nucleic Acid, Tacrolimus pharmacology
- Published
- 1991
49. The immunosuppressant FK-506 specifically inhibits mitogen-induced activation of the interleukin-2 promoter and the isolated enhancer elements NFIL-2A and NF-AT1.
- Author
-
Banerji SS, Parsons JN, and Tocci MJ
- Subjects
- Base Sequence, Cell Line, Cell Nucleus physiology, Chloramphenicol O-Acetyltransferase genetics, Chloramphenicol O-Acetyltransferase metabolism, DNA-Binding Proteins metabolism, Humans, Ionomycin pharmacology, Kinetics, Molecular Sequence Data, NF-kappa B genetics, Oligonucleotide Probes, Regulatory Sequences, Nucleic Acid drug effects, Retroviridae drug effects, Retroviridae genetics, TATA Box drug effects, Tacrolimus, Anti-Bacterial Agents pharmacology, Concanavalin A pharmacology, Enhancer Elements, Genetic drug effects, Gene Expression Regulation drug effects, Immunosuppressive Agents pharmacology, Interleukin-2 genetics, Promoter Regions, Genetic drug effects, Tetradecanoylphorbol Acetate pharmacology
- Abstract
The macrolide FK-506, like the cyclic undecapeptide cyclosporin A (CsA), is a potent immunosuppressant that interferes with the transcriptional activation of several early-phase genes in T lymphocytes, including that for interleukin-2 (IL-2). We compared the effects of FK-506 and CsA on transcription from the 5' upstream activating sequences (UAS) of the human IL-2 gene and several cellular and viral UAS to define cis-acting sites which may be responsive to FK-506. The UAS surveyed included the human IL-2 receptor alpha-chain, human metallothionein II, simian virus 40 early, human cytomegalovirus immediate-early, adenovirus major late, and Rous sarcoma virus long terminal repeat UAS. In addition, we studied multimers of several defined promoter elements (NFIL-2A, NF-kappa B, or NF-AT1) which are found in the UAS of the human IL-2 gene and which have been reported to be responsive to CsA when linked to a minimal promoter element (TATA box and transcription start site). Each promoter-regulatory region was fused to the bacterial chloramphenicol acetyltransferase gene and used to transiently transfect Jurkat cells. Quantitative chloramphenicol acetyltransferase assay determinations indicated that the transcriptional activity of each UAS induced upon T-cell activation was (i) completely sensitive, (ii) partially sensitive, or (iii) resistant to inhibition by CsA and FK-506. The induced transcription driven by the IL-2 promoter elements NF-AT1 and NFIL-2A could be blocked completely by FK-506 or CsA. Gel mobility shift assays indicated that the binding activities of the factors specifically interacting with these sequences were detected in activated cells regardless of whether the cells were treated with FK-506 or CsA. The results suggest that FK-506 or CsA inhibits a transacting mechanism(s) without disrupting the binding activities of these transcription factors. The degree to which each UAS was resistant to FK-506 was consistent with the level of transcription induced by phorbol myristate acetate, while UAS which were sensitive to inhibition by FK-506 were dependent on the presence of both phorbol myristate acetate and ionomycin.
- Published
- 1991
- Full Text
- View/download PDF
50. Probing the role of interleukin-1 beta convertase in interleukin-1 beta secretion.
- Author
-
Howard AD, Chartrain N, Ding GF, Kostura MJ, Limjuco G, Schmidt JA, and Tocci MJ
- Subjects
- Caspase 1, Cell Line, Humans, Interleukin-1 genetics, Endopeptidases physiology, Interleukin-1 metabolism, Metalloendopeptidases physiology, Monocytes enzymology
- Abstract
Interleukin-1 beta must be processed from its precursor form of 31.5 kDa to its mature form of 17 kDa in order to elaborate its wide array of bioactivities. The recent identification of a monocyte-specific endoprotease, termed interleukin-1 beta-converting enzyme (ICE), capable of generating authentic, bioactive 17 kDa IL-1 beta suggests that this protease may serve a specific role in the processing and subsequent secretion of IL-1 beta. To test this hypothesis, we describe initial attempts to establish a monocytic cell-based system to test if mutant preIL-1 beta molecules which are poor substrates for ICE in vitro will be processed and secreted by monocytic cells.
- Published
- 1991
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