90 results on '"Billings K"'
Search Results
2. Studies on core-swapped fibronectin type III domains
- Author
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Billings, K. S.
- Subjects
572.6 - Abstract
Two homologous fibronectin type III (fnIII) domains, FNfn10 (the tenth fibronectin type III domain of human fibronectin) and TNfn3 (the third fibronectin type III domain of human tenascin), have, essentially, the same backbone structure although they share only ~24% of sequence identity. FNoTNc is a core swapped protein, containing the “outside” (surface and loops) of FNfn10 and the hydrophobic core of TNfn3. Despite the extent of redesign, FNoTNc retains the structure of the parent proteins allowing us to gain insights into which components of each parent protein are responsible for different aspects of its behaviour. Naively, one would expect properties that depend principally on the core to be similar to TNfn3, for example the response to mutation, folding kinetics and sidechain dynamics; while properties determined by difference in the surface and loops, such as backbone dynamics, would be more like FNfn10. While this is broadly true, it is clear that there are also crosstalk effects between the core and surface. For example, the anomalous response of FNfn10 to mutation is not solely a core property as we had previously suggested. TNoFNc is a core swapped protein, containing the “outside” (surface and loops) of TNfn3 and the hydrophobic core of FNfn10. We infer from our data that TNoFNc has also retained the structure of the parent proteins. TNoFNc is a very unstable protein, which we suggest is due to over-packing of the core. An attempt was made to characterise mutants of TNoFNc, although our investigations were hampered by the presence of a possible impurity which may copurify with the mutant proteins. However, it is clear that the mutants appear to behave very differently to wild-type TNoFNc.
- Published
- 2007
3. Long-term (180-Day) Outcomes in Critically Ill Patients With COVID-19 in the REMAP-CAP Randomized Clinical Trial.
- Author
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Higgins, A.M., Berry, L.R., Lorenzi, E., Murthy, S., McQuilten, Z., Mouncey, P.R., Al-Beidh, F., Annane, D., Arabi, Y.M., Beane, A., Bentum-Puijk, W. van, Bhimani, Z., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Burrell, A., Buzgau, A., Buxton, M., Charles, W.N., Cove, M., Detry, M.A., Estcourt, L.J., Fagbodun, E.O., Fitzgerald, M., Girard, T.D., Goligher, E.C., Goossens, H., Haniffa, R., Hills, T., Horvat, C.M., Huang, D.T., Ichihara, N., Lamontagne, F., Marshall, J.C., McAuley, D.F., McGlothlin, A., McGuinness, S.P., McVerry, B.J., Neal, M.D., Nichol, A.D., Parke, R.L., Parker, J.C., Parry-Billings, K., Peters, S.E.C., Reyes, L.F., Rowan, K.M., Saito, H., Santos, M.S., Saunders, C.T., Serpa-Neto, A., Seymour, C.W., Shankar-Hari, M., Stronach, L.M., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Zarychanski, R., Green, C., Lewis, R.J., Angus, D.C., McArthur, C.J., Berry, S., Derde, L.P.G., Gordon, A.C., Webb, S.A., Lawler, P.R., Higgins, A.M., Berry, L.R., Lorenzi, E., Murthy, S., McQuilten, Z., Mouncey, P.R., Al-Beidh, F., Annane, D., Arabi, Y.M., Beane, A., Bentum-Puijk, W. van, Bhimani, Z., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Burrell, A., Buzgau, A., Buxton, M., Charles, W.N., Cove, M., Detry, M.A., Estcourt, L.J., Fagbodun, E.O., Fitzgerald, M., Girard, T.D., Goligher, E.C., Goossens, H., Haniffa, R., Hills, T., Horvat, C.M., Huang, D.T., Ichihara, N., Lamontagne, F., Marshall, J.C., McAuley, D.F., McGlothlin, A., McGuinness, S.P., McVerry, B.J., Neal, M.D., Nichol, A.D., Parke, R.L., Parker, J.C., Parry-Billings, K., Peters, S.E.C., Reyes, L.F., Rowan, K.M., Saito, H., Santos, M.S., Saunders, C.T., Serpa-Neto, A., Seymour, C.W., Shankar-Hari, M., Stronach, L.M., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Zarychanski, R., Green, C., Lewis, R.J., Angus, D.C., McArthur, C.J., Berry, S., Derde, L.P.G., Gordon, A.C., Webb, S.A., and Lawler, P.R.
- Abstract
Item does not contain fulltext, IMPORTANCE: The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown. OBJECTIVE: To determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes. DESIGN, SETTING, AND PARTICIPANTS: Prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022. INTERVENTIONS: Patients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401). MAIN OUTCOMES AND MEASURES: The main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83. RESULTS: Among 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06
- Published
- 2023
4. Long-term (180-day) outcomes in critically ill patients with COVID-19 in the REMAP-CAP randomized clinical trial
- Author
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Florescu, S, Stanciu, D, Zaharia, M, Kosa, A, Codreanu, D, Kidwai, A, Masood, S, Kaye, C, Coutts, A, MacKay, L, Summers, C, Polgarova, P, Farahi, N, Fox, E, McWilliam, S, Hawcutt, D, Rad, L, O’Malley, L, Whitbread, J, Jones, D, Dore, R, Saunderson, P, Kelsall, O, Cowley, N, Wild, L, Thrush, J, Wood, H, Austin, K, Bélteczki, J, Magyar, I, Fazekas, Á, Kovács, S, Szőke, V, Donnelly, A, Kelly, M, Smyth, N, O’Kane, S, McClintock, D, Warnock, M, Campbell, R, McCallion, E, Azaiz, A, Charron, C, Godement, M, Geri, G, Vieillard-Baron, A, Johnson, P, McKenna, S, Hanley, J, Currie, A, Allen, B, McGoldrick, C, McMaster, M, Mani, A, Mathew, M, Kandeepan, R, Vignesh, C, TV, B, Ramakrishnan, N, James, A, Elvira, E, Jayakumar, D, Pratheema, R, Babu, S, Ebenezer, R, Krishnaoorthy, S, Ranganathan, L, Ganesan, M, Shree, M, Guilder, E, Butler, M, Cowdrey, K-A, Robertson, M, Ali, F, McMahon, E, Duffy, E, Chen, Y, Simmonds, C, McConnochie, R, O’Connor, C, El-Khawas, K, Richardson, A, Hill, D, Commons, R, Abdelkharim, H, Saxena, M, Muteithia, M, Dobell-Brown, K, Jha, R, Kalogirou, M, Ellis, C, Krishnamurthy, V, O’Connor, A, Thurairatnam, S, Mukherjee, D, Kaliappan, A, Vertue, M, Nicholson, A, Riches, J, Maloney, G, Kittridge, L, Solesbury, A, Ramos, A, Collins, D, Brickell, K, Reid, L, Smyth, M, Breen, P, Spain, S, Curley, G, McEvoy, N, Geoghegan, P, Clarke, J, Silversides, J, McGuigan, P, Ward, K, O’Neill, A, Finn, S, Wright, C, Green, J, Collins, É, Knott, C, Smith, J, Boschert, C, Slieker, K, Ewalds, E, Sanders, A, Wittenberg, W, Geurts, H, Poojara, L, Sara, T, Nand, K, Reeve, B, Dechert, W, Phillips, B, Oritz-Ruiz de Gordoa, L, Affleck, J, Shaikh, A, Murray, A, Ramanan, M, Frakking, T, Pinnell, J, Robinson, M, Gledhill, L, Wood, T, Sanghavi, R, Bhonagiri, D, Ford, M, Parikh, HG, Avard, B, Nourse, M, McDonald, B, Edmunds, N, Hoiting, O, Peters, M, Rengers, E, Evers, M, Prinssen, A, Morgan, M, Cole, J, Hill, H, Davies, M, Williams, A, Thomas, E, Davies, R, Wise, M, Grimm, P, Soukup, J, Wetzold, R, Löbel, M, Starke, L, Lellouche, F, Lizotte, P, Declerq, P, Antoine, M, Stephanie, G, Jean-Pierre, E, François, B, Marion, B, Philippe, R, Pourcine, F, Monchi, M, Luis, D, Mercier, R, Sagnier, A, Verrier, N, Caplin, C, Richecoeu, J, Combaux, D, Siami, S, Aparicio, C, Vautier, S, Jeblaoui, A, Lemaire-Brunel, D, D'Aragon, F, Carbonneau, E, Leblond, J, Plantefeve, G, Leparco, C, Contou, D, Fartoukh, M, Courtin, L, Labbe, V, Voiriot, G, Salhi, S, Chassé, M, Carrier, F, Boumahni, D, Benettaib, F, Ghamraoui, A, Sement, A, Gachet, A, Hanisch, A, Haffiane, A, Boivin, A-H, Barreau, A, Guerineau, E, Poupblanc, S, Egreteau, P, Lefevre, M, Bocher, S, Le Loup, G, Le Guen, L, Carn, V, Bertel, M, Antcliffe, D, Templeton, M, Rojo, R, Coghlan, P, Smee, J, Barker, G, Finn, A, Kreb, G, Hoff, U, Hinrichs, C, Nee, J, Mackay, E, Cort, J, Whileman, A, Spencer, T, Spittle, N, Beavis, S, Padmakumar, A, Dale, K, Hawes, J, Moakes, E, Gascoyne, R, Pritchard, K, Stevenson, L, Cooke, J, Nemeth-Roszpopa, K, Gauli, B, Bastola, S, Muller, G, Nay, M-A, Kamel, T, Benzekri, D, Jacquier, S, Runge, I, Mathonnet, A, Barbier, F, Bretagnol, A, Carter, J, Van Der Heyden, K, Mehrtens, J, Morris, A, Morgan, S, Burke, T, Mercier, E, Chartier, D, Salmon, C, Dequin, P-F, Garot, D, Bellemare, D, Cloutier, È, Daher, R, Costerousse, O, Boulanger, M-C, Couillard-Chénard, É, Lauzier, F, Francoeur, C, Francois, B, Gay, A, Anne-Laure, F, Ramali, M, HC, O, Ghosh, A, Osagie, R, Arachchige, M, Hartley, M, Cheung, W, Wong, H, Seigne, P, Eustace, J, O'Callaghan, A-M, O'Brien, F, Bamford, P, Reid, A, Cawley, K, Faulkner, M, Pickering, C, Raj, A, Tsinaslanidis, G, Khade, R, Agha, G, Sekiwala, R, Smith, T, Brewer, C, Gregory, J, Limb, J, Cowton, A, O’Brien, J, Postlethwaite, K, Malakouti, S, Music, E, Ricketts, D, King, A, Clermont, G, Bart, R, Mayr, F, Schoenling, A, Andreae, M, Shetty, V, Brant, E, Malley, B, Donadee, C, Sackrowitz, R, Weissman, A, Yealy, D, Barton, D, Talia, N, Nikitas, N, Wells, C, Lankester, L, McMillan, H, Van den Oever, H, Kruisdijk-Gerritsen, A, Haidar, G, Bain, W, Barbash, I, Fitzpatrick, M, Franz, C, Kitsios, G, Moghbeli, K, Rosborough, B, Shah, F, Suber, T, Pulletz, M, Williams, P, Birch, J, Wiseman, S, Horton, S, Alegria, A, Turki, S, Elsefi, T, Crisp, N, Allen, L, Truman, N, Smith, M, Chukkambotla, S, Goddard, W, Duberley, S, Khan, M, Kazi, A, Simpson, J, Duke, G, Chan, P, Carter, B, Hunter, S, Voigt, I, Schueler, R, Blank, E, Hüning, V, Steffen, M, Goralski, P, Litton, E, Regli, A, Pellicano, S, Palermo, A, Eroglu, E, Bihari, S, Laver, RD, Jin, X, Brown, J, McIntyre, J, French, C, Bates, S, Towns, M, Yang, Y, McGain, F, McCullagh, I, Cairns, T, Hanson, H, Patel, B, Clement, I, Evetts, G, Touma, O, Holland, S, Hodge, C, Taylor, H, Alderman, M, Barnes, N, Da Rocha, J, Smith, C, Brooks, N, Weerasinghe, T, Sinclair, J-A, Abusamra, Y, Doherty, R, Cudlipp, J, Singh, R, Yu, H, Daebis, A, Ng, C, Kendrick, S, Saran, A, Makky, A, Greener, D, Rowe-Leete, L, Edwards, A, Bland, Y, Dolman, R, Foster, T, Laffey, J, McNicholas, B, Scully, M, Casey, S, Kernan, M, Brennan, A, Rangan, R, Tully, R, Corbett, S, McCarthy, A, Duffy, O, Burke, D, Linnett, V, Sanderson, A, Ritzema, J, Wild, H, Lucas, R, Marriott, Y, Andric, Z, Cviljevic, S, Br, R, Zapalac, M, Mirković, G, Khare, D, Pinder, M, Gopinath, A, Kannan, T, Dean, S, Vanmali, P, Depuydt, P, De Waele, J, De Bus, L, Fierens, J, Bracke, S, Vermassen, J, Vermeiren, D, Pugh, R, Lean, R, Qiu, X, Scanlan, J, Evans, A, Davies, G, Lewis, J, Plesnikova, Y, Khoud, A, Coetzee, S, Puxty, K, Cathcart, S, Rimmer, D, Bagot, C, Scott, K, Martin, L, Yusuff, H, Isgro, G, Brightling, C, Bourne, M, Craner, M, Boyles, R, Alexander, B, Roberts, T, Nelli, A, Rosenstein-Sisson, R, Speyer, R, Pech, Y, McCullough, J, Tallott, M, Vazquez-Grande, G, Marten, N, Liu, T, Siddiqui, A, Khanal, S, Amatya, S, Szakmany, T, Cherian, S, Williams, G, James, C, Waters, A, Prout, R, Stedman, R, Davies, L, Pegler, S, Kyeremeh, L, Moorhouse, L, Arbane, G, Marotti, M, Bociek, A, Campos, S, Van Nieuwkoop, K, Ottens, T, Visser, Y, Van den Berg, L, Van der Kraan-Donker, A, Brett, S, Arias, S, Hall, R, Paneru, H, Koirala, S, Paudel, P, Wilson, M, Vaara, S, Pettilä, L, Heinonen, J, Pettilä, V, Jain, S, Gupta, A, Holbrook, C, Antoine, P, Meziani, F, Allam, H, Cattelan, J, Clere-Jehl, R, Helms, J, Kummerlen, C, Merdji, H, Monnier, A, Rahmani, H, Studer, A, Schneider, F, Castelain, V, Morel, G, L’Hotellier, S, Ochin, E, Vanjak, C, Rouge, P, Bendjemar, L, Albert, M, Serri, K, Cavayas, A, Duplaix, M, Williams, V, Catorze, NJTADS, Pereira, TNAL, Ferreira, RMC, Bastos, JMPS, Batista, TMO, Badie, J, Berdaguer, F, Malfroy, S, Mezher, C, Bourgoin, C, Moneger, G, Bouvier, E, Muñoz-Bermúdez, R, Marin-Corral, J, Degracia, A, Gómez, F, López, M, Aceto, R, Aghemo, A, Badalamenti, S, Brunetta, E, Cecconi, M, Ciccarelli, M, Constantini, E, Greco, M, Folci, M, Selmi, C, Voza, A, Henning, J, Bonner, S, Hugill, K, Cirstea, E, Wilkinson, D, Jones, J, Altomy, M, Karlikowski, M, Sutherland, H, Wilhelmsen, E, Woods, J, North, J, Pletz, M, Hagel, S, Ankert, J, Kolanos, S, Bloos, F, Simons, K, Van Zuylen, T, Bouman, A, Kumar, N, Panwar, R, Poulter, A-L, Sunkara, K, Szigligeti, G, Leszkoven, J, Rochwerg, B, Karachi, T, Oczkowski, S, Centofanti, J, Millen, T, Sundaran, D, Hollos, L, Turns, M, Walsh, J, Al Qasim, E, Alswaidan, L, Hegazy, M, Arishi, H, Al Amri, A, AlQahtani, S, Naidu, B, Tlayjeh, H, Hussain, S, Al Enezi, F, Abdukahil, SA, Hopkins, P, Noble, H, O’Reilly, K, Mehta, R, Wong, O, Makanju, E, Rao, D, Sikondari, N, Saha, S, Corcoran, E, Pappa, E, Cockrell, M, Donegan, C, Balaie, M, Nickoleit-Bitzenberger, D, Schaaf, B, Meermeier, W, Prebeg, K, Azzaui, H, Hower, M, Brieger, K-G, Elender, C, Sabelhaus, T, Riepe, A, Akamp, C, Kremling, J, Klein, D, Landsiedel-Mechenbier, E, Laha, S, Verlander, M, Jha, A, Megarbane, B, Voicu, S, Deye, N, Malissin, I, Sutterlin, L, Mrad, A, Lehalleur, A, Naim, G, Nguyen, P, Ekhérian, J-M, Boué, Y, Sidéris, G, Vodovar, D, Guérin, E, Grant, C, Brain, M, Mineall, S, Paramasivam, E, Wilby, E, Ogg, B, Howcroft, C, Aspinwall, A, Charlton, S, Gould, R, Mistry, D, Awan, S, Bedford, C, Carr-Wilkinson, J, Hall, A, Gardiner-Hill, C, Maloney, C, Brunskill, N, Watchorn, O, Hardy, C, Qureshi, H, Flint, N, Nicholson, S, Southin, S, Ghattaoraya, A, Harding, D, O’Halloran, S, Collins, A, Smith, E, Trues, E, Borgatta, B, Turner-Bone, I, Reddy, A, Wilding, L, Wilson, C, Surti, Z, Aneman, A, Miller, J, White, H, Estensen, K, Morrison, L, Sutton, J, Cooper, M, Warnapura, L, Agno, R, Sathianathan, P, Shaw, D, Ijaz, N, Spong, A, Sabaretnam, S, Burns, D, Lang, E, Tate, M, Fischer, R, Biradar, V, Soar, N, Golden, D, Davey, M, Seaman, R, Osborne, A, Bannard-Smith, J, Clark, R, Birchall, K, Henry, J, Pomeroy, F, Quayle, R, Wylie, K, Sukuraman, A, John, M, Sibin, S, Leditschke, A, Finnis, M, Jongebloed, K, Khwaja, K, Campisi, J, Van Vonderen, M, Pietersma, M, Vrolijk, L, Kampschreur, L, Van Gulik, L, Makowski, A, Misztal, B, Haider, S, Liao, A, Squires, R, Oborska, A, Kayani, A, Kalchko-Veyssal, S, Prabakaran, R, Hadebe, B, KalchkoVeyssal, S, Williams, T, Song, R, Morpeth, S, Lai, V, Habraken, H, Stewart, R, Mwaura, E, Mew, L, Wren, L, Willams, F, Sutherland, S-B, Rebello, R, Shehabi, Y, Al-Bassam, W, Hulley, A, Kadam, U, Sathianathan, K, Innes, R, Doble, P, Graham, L, Shovelton, C, Dean, T, Salahuddin, N, Aryal, D, Koirala, K, Rai, N, Luitel, S, Seppelt, I, Whitehead, C, Lowrey, J, Gresham, R, Masters, K, Hamlyn, V, Hawkins, N, Roynon-Reed, A, Cutler, S, Lewis, S, Lazaro, J, Newman, T, Aravindan, L, Asghar, A, Bartholomew, J, Bayne, M, Beddows, S, Birch, C, Brend, M, Byrne, R, Campbell, D, Campbell, H, Chambers, E, Clinton, A, Collins, J, Crawshaw, S, Dawson, LA, Donaldson, K, Drake, C, Dyas, S, Ellis, Y, Gilmour, K, Goodwin, J, Halden, S, Hall, AS, Hanson, J, Harper, H, Harrison, S, Hayes, A, Hodgson, H, Hurford, S-A, Jackson, S, Levett, C, Lock, S, Lockett, T, Logan, M, Lomme, K, Luo, J, Marsh, E, Mguni, N, Monaghan, H, Murphy, S, Muzengi, N, Naz, M, O'Kell, E, Oliver, A, O'Reilly, J, Pearson, K, Porter, D, Potter, A, Rook, C, Rounds, C, Sheffield, J, Shirley, K, Siewersk, C, Skinner, T, Speight, H, Sutu, M, Unsworth, A, Van’t Hoff, W, Walker, S, Williams, H, Williamson, D, Williamson, JD, Duan, E, Tsang, J, Patterson, L, Austin, P, Chapman, S, Cabrelli, L, Fletcher, S, Nortje, J, Fottrell-Gould, D, Randell, G, Stammers, K, Healey, G, Pinto, M, Borrill, Z, Duncan, T, Ustianowski, A, Uriel, A, Eltayeb, A, Alfonso, J, Hey, S, Shaw, J, Fox, C, Lindergard, G, Charles, B, Blackledge, B, Connolly, K, Harris, J, Cuesta, J, Xavier, K, Purohit, D, Elhassan, M, Haldeos, A, Vincent, R, Abdelrazik, M, Jenkins, S, Ganesan, A, Kumar, R, Carter, D, Bakthavatsalam, D, Frater, A, Saleem, M, Everitt, R, Hacking, D, Zaman, M, Elmahi, E, Jones, A, Hall, K, Phillips, M, Terrill, L, Mills, G, Raithatha, A, Bauchmuller, K, Ryalls, K, Harrington, K, Bowler, H, Sall, J, Bourne, R, Gross, J, Massey, N, Adebambo, O, Long, M, Tony, K, Juffermans, N, Koopmans, M, Dujardin, R, Alderink, B, Rowland, M, Hutton, P, Bashyal, A, Davidson, N, Hird, C, Chhablani, M, Phalod, G, Kirkby, A, Archer, S, Netherton, K, Reschreiter, H, Camsooksai, J, Patch, S, Humphrey, C, Flynn, G, Harrington, C, Kruger, P, Walsham, J, Meyer, J, Harward, M, Jones, C, Sathe, S, Roche, L, Davies, E, Skinner, D, Gaylard, J, Newman, J, Pogson, D, Rose, S, Daly, Z, Brimfield, L, Nown, A, Parekh, D, Bergin, C, Bates, M, McGhee, C, Lynch, D, Bhandal, K, Tsakiridou, K, Bamford, A, Cooper, L, Whitehouse, T, Veenith, T, Forster, E, O'Connell, M, Sim, M, Hay, S, Henderson, S, Nygren, M, Valentine, E, Katary, A, Bell, G, Wilcox, L, Mataliotakis, M, Smith, P, Ali, M, Isguzar, A, Phull, M-K, Zaidi, A, Pogreban, T, Rosaroso, L, Harvey, D, Lowe, B, Meredith, M, Ryan, L, Schouten, J, Pickkers, P, Roovers, N, Klop-Riehl, M, Van der Eng, H, Sloots-Cuppen, S, Preijers, L, Van Oosten, N, Moine, P, Heming, N, Maxime, V, Bossard, I, Nicholier, T, Clair, B, Orlikowski, D, Bounab, R, Abdeladim, L, Baker, S, Duroux, M, Ratcliffe, M, Sy, E, Mailman, J, Lee, S, Gupta, C, Kassir, S, López, R, Rodríguez-Gómez, J, Cárcel, S, Carmona, R, De la Fuente, C, Rodriguez, M, Jan Hassing, R, Greven, F, Huijbens, D, Roebers, L, Verheij, H, Miles, H, Attokaran, A, Buehner, U, Williams, E, Chapman, M, O’Connor, S, Glasby, K, Rivett, J, Brown, N, Kutsogiannis, D, Thompson, P, Rooney, K, Rodden, N, Thomson, N, McGlynn, D, Abel, L, Gemmell, L, Sundaram, R, Hornsby, J, Walden, A, Keating, L, Frise, M, Rai, S, Bartley, S, Schuster-Bruce, M, Pitts, S, Miln, R, Purandare, L, Vamplew, L, Dempster, D, Gummadi, M, Dormand, N, Wang, S, Spivey, M, Bean, S, Burt, K, Moore, L, Hammonds, F, Richards, C, Campbell, L, Smyth, K, Day, C, Zitter, L, Benyon, S, Singh, J, Lynch, C, Mikusek, J, Deacon, B, Turner, K, Baker, E, Hickey, J, Champanerkar, S, Aitken, L, LewisProsser, L, Ahmad, N, Wiles, M, Willson, J, Grecu, I, Martin, 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McIntyre, L, Brady, K, Vale, C, Shekar, K, Lavana, J, Parmar, D, Peake, S, Kurenda, C, Hormis, A, Walker, R, Collier, D, Kimpton, S, Oakley, S, Bhagani, S, De Neef, M, Garcia, S, Maharajh, A, Nandani, A, Dobson, J, Fernando, G, Eastgate, C, Gomez, K, Abdi, Z, Tatham, K, Jhanji, S, Black, E, Dela Rosa, A, Howle, R, Baikady, R, Drummond, A, Dearden, J, Philbin, J, Munt, S, Gopal, S, Pooni, J-S, Ganguly, S, Smallwood, A, Metherell, S, Naeem, A, Fagan, L, Ryan, E, Mariappa, V, Foulds, A, Revill, A, Bhattarai, B, De Jonge, E, Wigbers, J, Del Prado, M, Cremer, O, Mulier, J, Peters, A, Romberg, B, Schutgens, R, Troeman, D, Van Opdorp, M, Besten, H, Brakké, K, Barber, R, Hilldrith, A, Kluge, S, Nierhaus, A, Jarczak, D, Roedl, K, Kochanek, M, Rueß-Paterno, G, Mc-Kenzie, J, Eichenauer, D, Shimabukuro-Vornhagen, A, Wilcox, E, Del Sorbo, L, Abdelhady, H, Romagnuolo, T, Simpson, S, Maiden, M, Horton, M, Trickey, J, Krajinovic, V, Kutleša, M, Kotarski, V, Brohi, F, Jagannathan, V, Clark, M, Purvis, S, Wetherill, B, Brajković, A, Babel, J, Sever, H, Dragija, L, Kušan, I, Dushianthan, A, Cusack, R, De Courcy-Golder, K, Salmon, K, Burnish, R, Smith, S, Ruiz, W, Duke, Z, Johns, M, Male, M, Gladas, K, Virdee, S, Swabe, J, Tomlinson, H, Rohde, G, Grünewaldt, A, Bojunga, J, Petros, S, Kunz, K, Schütze, B, Weismann, D, Frey, A, Drayss, M, Goebeler, ME, Flor, T, Fragner, G, Wahl, N, Totzke, J, Sayehli, C, Hakak, S, Altaf, W, O'Sullivan, M, Murphy, A, Walsh, L, Rega La Valle, A, Bewley, J, Sweet, K, Grimmer, L, Johnson, R, Wyatt, R, Morgan, K, Varghese, S, Willis, J, Stratton, E, Kyle, L, Putensen, D, Drury, K, Skorko, A, Bremmer, P, Ward, G, Bassford, C, Sligl, W, Baig, N, Rewa, O, Bagshaw, S, Basile, K, Stavor, D, Burbee, D, McNamara, A, Wunderley, R, Bensen, N, Adams, P, Vita, T, Buhay, M, Scholl, D, Gilliam, M, Winters, J, Doherty, K, Berryman, E, Ghaffari, M, Marroquin, O, Quinn, K, Garrard, W, Kalchthaler, K, Beard, G, Skrtich, A, Bagavathy, K, Drapola, D, Bryan-Morris, K, Arnold, J, 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AF, Turner, AM, Van de Veerdonk, FL, Zarychanski, R, Green, C, Lewis, RJ, Angus, DC, McArthur, CJ, Berry, S, Derde, LPG, Gordon, AC, Webb, SA, Lawler, PR, Comm REMAP-CAP Investigators, Apollo - University of Cambridge Repository, Intensive Care Medicine, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Raymond Poincaré [Garches], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pittsburgh Foundation, PF, Amgen, Health Research Board, HRB: CTN 2014-012, Horizon 2020 Framework Programme, H2020: 101003589, Translational Breast Cancer Research Consortium, TBCRC, Canadian Institutes of Health Research, IRSC: 158584, Heart and Stroke Foundation of Canada, HSF, National Institute for Health and Care Research, NIHR, European Commission, EC, National Health and Medical Research Council, NHMRC: 1101719, APP194811, CS-2016-16-011, GNT2008447, RP-2015-06-18, Office of Health and Medical Research, OHMR, Health Research Council of New Zealand, HRC: 16/631, Eisai, Ministère des Affaires Sociales et de la Santé: PHRC-20-0147, Université Pierre et Marie Curie, UPMC, NIHR Imperial Biomedical Research Centre, BRC, Minderoo Foundation, Funding/Support : The Platform for European Preparedness Against (Re-) emerging Epidemics (PREPARE) consortium by the European Union, FP7-HEALTH-2013-INNOVATION-1 (#602525), the Rapid European COVID-19 Emergency Research response (RECOVER) consortium by the European Union’s Horizon 2020 research and innovation programme (#101003589), the Australian National Health and Medical Research Council (#APP1101719), the Australian Medical Research Future Fund (#APP2002132), the Health Research Council of New Zealand (#16/631), the Canadian Institutes of Health Research Strategy for Patient-Oriented Research Innovative Clinical Trials Program Grant (#158584) and the Canadian Institute of Health Research COVID-19 Rapid Research Funding (#447335), the UK National Institute for Health Research (NIHR) and the NIHR Imperial Biomedical Research Centre, the Health Research Board of Ireland (CTN 2014-012), the UPMC Learning While Doing Program, the Translational Breast Cancer Research Consortium, the French Ministry of Health (PHRC-20-0147), the Wellcome Trust Innovations Project (215522), the Minderoo Foundation, the EU Programme Emergency Support Instrument, the NHS Blood and Transplant Research and Development Programme, the Translational Breast Cancer Research Consortium, the NSW Office of Health and Medical Research, Amgen, Eisai, and the Pittsburgh Foundation. Dr Higgins is funded by an NHMRC Emerging Leadership Fellowship (GNT2008447). Dr McQuilten is funded by an NHMRC Emerging Leadership Fellowship (APP194811). Dr Gordon is funded by an NIHR Research Professorship (RP-2015-06-18) and Dr Shankar-Hari by an NIHR Clinician Scientist Fellowship (CS-2016-16-011). Dr Turgeon is the Chairholder of the Canada Research Chair in Critical Care Neurology and Trauma. Dr Lawler is supported by a career award from the Heart and Stroke Foundation of Canada., and European Project: 602525,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,PREPARE(2014)
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Adult ,Male ,corticosteroid ,[SDV]Life Sciences [q-bio] ,Critical Illness ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,antiplatelet ,Lopinavir ,Adaptive platform trial randomized controlled trial intensive care, pneumonia COVID-19 antiplatelet immunoglobulin antiviral corticosteroid immune modulation anticoagulation ,All institutes and research themes of the Radboud University Medical Center ,Adrenal Cortex Hormones ,Humans ,anticoagulation ,intensive care, pneumonia ,COVID-19 Serotherapy ,Original Investigation ,Medicine(all) ,immune modulation ,Ritonavir ,SARS-CoV-2 ,COVID-19 ,Anticoagulants ,Bayes Theorem ,General Medicine ,Middle Aged ,antiviral ,Receptors, Interleukin-6 ,Adaptive platform trial ,randomized controlled trial ,Female ,Human medicine ,immunoglobulin ,Follow-Up Studies ,Hydroxychloroquine - Abstract
ImportanceThe longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown.ObjectiveTo determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes.Design, Setting, and ParticipantsPrespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022.InterventionsPatients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401).Main Outcomes and MeasuresThe main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83.ResultsAmong 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06 [95% CrI, 0.82-1.38]) and the probabilities of harm from hydroxychloroquine (96.9%; HR, 1.51 [95% CrI, 0.98-2.29]) and the combination of lopinavir-ritonavir and hydroxychloroquine (96.8%; HR, 1.61 [95% CrI, 0.97-2.67]) were high. The corticosteroid domain was stopped early prior to reaching a predefined statistical trigger; there was a 57.1% to 61.6% probability of improving 6-month survival across varying hydrocortisone dosing strategies.Conclusions and RelevanceAmong critically ill patients with COVID-19 randomized to receive 1 or more therapeutic interventions, treatment with an IL-6 receptor antagonist had a greater than 99.9% probability of improved 180-day mortality compared with patients randomized to the control, and treatment with an antiplatelet had a 95.0% probability of improved 180-day mortality compared with patients randomized to the control. Overall, when considered with previously reported short-term results, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months.
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- 2023
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5. Science Goals and Mission Architecture of the Europa Lander Mission Concept
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Hand, K. P., primary, Phillips, C. B., additional, Murray, A., additional, Garvin, J. B., additional, Maize, E. H., additional, Gibbs, R. G., additional, Reeves, G., additional, Martin, A. M. San, additional, Tan-Wang, G. H., additional, Krajewski, J., additional, Hurst, K., additional, Crum, R., additional, Kennedy, B. A., additional, McElrath, T. P., additional, Gallon, J. C., additional, Sabahi, D., additional, Thurman, S. W., additional, Goldstein, B., additional, Estabrook, P., additional, Lee, S. W., additional, Dooley, J. A., additional, Brinckerhoff, W. B., additional, Edgett, K. S., additional, German, C. R., additional, Hoehler, T. M., additional, Hörst, S. M., additional, Lunine, J. I., additional, Paranicas, C., additional, Nealson, K., additional, Smith, D. E., additional, Templeton, A. S., additional, Russell, M. J., additional, Schmidt, B., additional, Christner, B., additional, Ehlmann, B., additional, Hayes, A., additional, Rhoden, A., additional, Willis, P., additional, Yingst, R. A., additional, Craft, K., additional, Cameron, M. E., additional, Nordheim, T., additional, Pitesky, J., additional, Scully, J., additional, Hofgartner, J., additional, Sell, S. W., additional, Barltrop, K. J., additional, Izraelevitz, J., additional, Brandon, E. J., additional, Seong, J., additional, Jones, J.-P., additional, Pasalic, J., additional, Billings, K. J., additional, Ruiz, J. P., additional, Bugga, R. V., additional, Graham, D., additional, Arenas, L. A., additional, Takeyama, D., additional, Drummond, M., additional, Aghazarian, H., additional, Andersen, A. J., additional, Andersen, K. B., additional, Anderson, E. W., additional, Babuscia, A., additional, Backes, P. G., additional, Bailey, E. S., additional, Balentine, D., additional, Ballard, C. G., additional, Berisford, D. F., additional, Bhandari, P., additional, Blackwood, K., additional, Bolotin, G. S., additional, Bovre, E. A., additional, Bowkett, J., additional, Boykins, K. T., additional, Bramble, M. S., additional, Brice, T. M., additional, Briggs, P., additional, Brinkman, A. P., additional, Brooks, S. M., additional, Buffington, B. B., additional, Burns, B., additional, Cable, M. L., additional, Campagnola, S., additional, Cangahuala, L. A., additional, Carr, G. A, additional, Casani, J. R., additional, Chahat, N. E., additional, Chamberlain-Simon, B. K., additional, Cheng, Y., additional, Chien, S. A., additional, Cook, B. T., additional, Cooper, M., additional, DiNicola, M., additional, Clement, B., additional, Dean, Z., additional, Cullimore, E. A., additional, Curtis, A. G., additional, Croix, J-P. de la, additional, Pasquale, P. Di, additional, Dodd, E. M., additional, Dubord, L. A., additional, Edlund, J. A., additional, Ellyin, R., additional, Emanuel, B., additional, Foster, J. T., additional, Ganino, A. J., additional, Garner, G. J., additional, Gibson, M. T., additional, Gildner, M., additional, Glazebrook, K. J., additional, Greco, M. E., additional, Green, W. M., additional, Hatch, S. J., additional, Hetzel, M. M., additional, Hoey, W. A., additional, Hofmann, A. E., additional, Ionasescu, R., additional, Jain, A., additional, Jasper, J. D., additional, Johannesen, J. R., additional, Johnson, G. K., additional, Jun, I., additional, Katake, A. B., additional, Kim-Castet, S. Y., additional, Kim, D. I., additional, Kim, W., additional, Klonicki, E. F., additional, Kobeissi, B., additional, Kobie, B. D., additional, Kochocki, J., additional, Kokorowski, M., additional, Kosberg, J. A., additional, Kriechbaum, K., additional, Kulkarni, T. P., additional, Lam, R. L., additional, Landau, D. F., additional, Lattimore, M. A., additional, Laubach, S. L., additional, Lawler, C. R., additional, Lim, G., additional, Lin, J. Y, additional, Litwin, T. E., additional, Lo, M. W., additional, Logan, C. A., additional, Maghasoudi, E., additional, Mandrake, L., additional, Marchetti, Y., additional, Marteau, E., additional, Maxwell, K. A., additional, Namee, J. B. Mc, additional, Mcintyre, O., additional, Meacham, M., additional, Melko, J. P., additional, Mueller, J., additional, Muliere, D. A., additional, Mysore, A., additional, Nash, J., additional, Ono, H., additional, Parker, J. M., additional, Perkins, R. C., additional, Petropoulos, A. E, additional, Gaut, A., additional, Gomez, M. Y. Piette, additional, Casillas, R. P., additional, Preudhomme, M., additional, Pyrzak, G., additional, Rapinchuk, J., additional, Ratliff, J. M., additional, Ray, T. L., additional, Roberts, E. T., additional, Roffo, K., additional, Roth, D. C., additional, Russino, J. A., additional, Schmidt, T. M., additional, Schoppers, M. J., additional, Senent, J. S., additional, Serricchio, F., additional, Sheldon, D. J., additional, Shiraishi, L. R., additional, Shirvanian, J., additional, Siegel, K. J., additional, Singh, G., additional, Sirota, A. R., additional, Skulsky, E. D., additional, Stehly, J. S., additional, Strange, N. J., additional, Stevens, S. U., additional, Sunada, E. T., additional, Tepsuporn, S. P., additional, Tosi, L. P. C., additional, Trawny, N., additional, Uchenik, I., additional, Verma, V., additional, Volpe, R. A., additional, Wagner, C. T., additional, Wang, D., additional, Willson, R. G., additional, Wolff, J. L., additional, Wong, A. T., additional, Zimmer, A. K., additional, Sukhatme, K. G., additional, Bago, K. A., additional, Chen, Y., additional, Deardorff, A. M., additional, Kuch, R. S., additional, Lim, C., additional, Syvertson, M. L., additional, Arakaki, G. A., additional, Avila, A., additional, DeBruin, K. J., additional, Frick, A., additional, Harris, J. R., additional, Heverly, M. C., additional, Kawata, J. M., additional, Kim, S.-K., additional, Kipp, D. M., additional, Murphy, J., additional, Smith, M. W., additional, Spaulding, M. D., additional, Thakker, R., additional, Warner, N. Z., additional, Yahnker, C. R., additional, Young, M. E., additional, Magner, T., additional, Adams, D., additional, Bedini, P., additional, Mehr, L., additional, Sheldon, C., additional, Vernon, S., additional, Bailey, V., additional, Briere, M., additional, Butler, M., additional, Davis, A., additional, Ensor, S., additional, Gannon, M., additional, Haapala-Chalk, A., additional, Hartka, T., additional, Holdridge, M., additional, Hong, A., additional, Hunt, J., additional, Iskow, J., additional, Kahler, F., additional, Murray, K., additional, Napolillo, D., additional, Norkus, M., additional, Pfisterer, R., additional, Porter, J., additional, Roth, D., additional, Schwartz, P., additional, Wolfarth, L., additional, Cardiff, E. H., additional, Grob, E. W., additional, Adam, J. R., additional, Betts, E., additional, Norwood, J., additional, Heller, M. M., additional, Voskuilen, T., additional, Sakievich, P., additional, Gray, L., additional, Hansen, D. J., additional, Irick, K. W., additional, Hewson, J. C., additional, Lamb, J., additional, Stacy, S. C., additional, Brotherton, C. M., additional, Tappan, A. S, additional, Benally, D., additional, Thigpen, H., additional, Ortiz, E., additional, Sandoval, D., additional, Ison, A. M., additional, Warren, M., additional, Stromberg, P. G., additional, Thelen, P. M., additional, Blasy, B., additional, Nandy, P., additional, Haddad, A. W., additional, Trujillo, L. B., additional, Wiseley, T. H., additional, Bell, S. A., additional, Teske, N. P., additional, Post, C., additional, Torres-Castro, L., additional, Grosso, C., additional, and Wasiolek, M., additional
- Published
- 2022
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6. Individual responsibilities in multidisciplinary working
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Morton, R.E, Billings, K, Hankinson, J, Hart, D, Nicholson, J, Rowlands, A, Saunders, R, and Walter, A
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- 2003
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7. (274) Pediatric return visits to the emergency department for postoperative pain
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Manworren, R., primary, Billings, K., additional, Stake, C., additional, Hebal, F., additional, Bhushan, B., additional, Hoeman, E., additional, Duggan, S., additional, Birmingham, P., additional, Shah, R., additional, Davis, M., additional, and Barsness, K., additional
- Published
- 2017
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8. Manipulating the stability of fibronectin type III domains by protein engineering
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Ng, Sean P, primary, Billings, K S, additional, Randles, L G, additional, and Clarke, Jane, additional
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- 2008
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9. MENTAL PRACTICE AND MOTOR LEARNING OF A FUNCTIONAL MOTOR TASK IN OLDER ADULTS.
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Tunney, N., primary, Billings, K., additional, Jackson, K., additional, Blakely, B., additional, Hill, M., additional, and Burch, D., additional
- Published
- 2005
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10. Learning to live in a medical household
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Billings, K., primary
- Published
- 2004
- Full Text
- View/download PDF
11. Exploiting upper and lower bounds in top-down query optimization.
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Shapiro, L., Maier, D., Benninghoff, P., Billings, K., Fan, Y., Hatwal, K., Wang, Q., Zhang, Y., Wu, H.-M., and Vance, B.
- Published
- 2001
- Full Text
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12. Deletion Analysis of the p16/CDKN2 Gene in Head and Neck Squamous Cell Carcinoma Using Quantitative Polymerase Chain Reaction Method
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Rawnsley, J. D., primary, Srivatsan, E. S., additional, Chakrabarti, R., additional, Billings, K. R., additional, and Wang, M. B., additional
- Published
- 1997
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13. Suppressive factor or factors derived from head and neck squamous cell carcinoma induce apoptosis in activated lymphocytes
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BILLINGS, K, primary, WANG, M, additional, and LICHTENSTEIN, A, additional
- Published
- 1997
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14. Clinical and pathologic distinction between primary and metastatic mucosal melanoma of the head and neck
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BILLINGS, K, primary, WANG, M, additional, SERCARZ, J, additional, and FU, Y, additional
- Published
- 1995
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15. Ventilatory responses to progressive hypoxia and hypercapnia in developing sheep
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Moss, T.J., primary, Jakubowska, A.E., additional, McCrabb, G.J., additional, Billings, K., additional, and Harding, R., additional
- Published
- 1995
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16. Respiratory Function in Lambs after Prolonged Oligohydramnios during Late Gestation
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Jakubowska, A E, primary, Billings, K, additional, Johns, D P, additional, Hooper, S B, additional, and Harding, R, additional
- Published
- 1993
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17. Relationship between dietary, serum, and tissue levels of carotenoids
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Cooney, R.V., primary, Bertram, J.S., additional, Hankin, J.H., additional, Kolonel, L.N., additional, Miyake, A., additional, Billings, K., additional, and Bourne, W., additional
- Published
- 1991
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18. Mental practice and motor learning of a functional motor task in older adults: a pilot study.
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Tunney N, Billings K, Blakely BG, Burch D, Hill M, and Jackson K
- Abstract
The purpose of this study was to examine the influence of mental practice on retention of a newly learned functional motor task in older adults. Nineteen non-demented community-dwelling older adults were randomly assigned to experimental and control groups and received a session of individual instruction in a novel motor task. Subjects were scored on their performance of the motor task on the final practice trial of the training session, and again 48-72 hours later. The experimental group mentally rehearsed the procedure 4 times in the 48 hour interval between training and testing while control subjects did not. Subjects in the experimental group scored significantly higher on the test day than the control subjects (p < 1.0), and difference scores from training to testing dates were significantly different between groups (p < 0.50). These findings suggest that for older adults, mental practice facilitates retention of a newly learned functional motor task. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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19. Challenges Facing Social Enterprises in the United States
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Abramson Alan J. and Billings Kara C.
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social enterprise ,United States ,Social pathology. Social and public welfare. Criminology ,HV1-9960 - Abstract
Hybrid organizations that combine social purpose and profit motive appear to have grown significantly in number in the U.S. in recent decades. However, these organizations, which we call “social enterprises,” face challenges that impede their growth and hinder their ability to deliver greater benefits. To better understand what these challenges are, this paper surveys the growing literature on social enterprises which suggests that social enterprises now face these major obstacles: ill-fitting legal forms, obstacles to effective governance, problems in evaluating impact, weak supportive networks, difficulties in raising funding, and management tensions. Deepening understanding of the challenges facing social enterprises should help guide those interested in strengthening public policy toward social enterprise and other aspects of the support system for these organizations.
- Published
- 2019
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20. Comparison of omeprazole and histamine H2-receptor antagonists in the treatment of elderly and young patients with reflux oesophagitis.
- Author
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James, O F and Parry-Billings, K S
- Abstract
Retrospective analyses of two multicentre clinical trials were carried out to examine the association of age with endoscopically verified reflux oesophagitis lesions and symptoms before and after 4 or, if necessary, 8 weeks randomized double-blind treatment with omeprazole (20 mg o.m.) or histamine H2-receptor antagonists (H2RA) (cimetidine 400 mg q.d.s. or ranitidine 150 mg b.d.). Of the elderly patients (> or = 65 years) 79 received omeprazole, 39 cimetidine and 36 ranitidine; of the young patients (< 65 years) 200 received omeprazole, 94 cimetidine and 102 ranitidine. The objective of treatment was to heal the oesophagus and to relieve the patient's symptoms. On completion of the studies the proportion of elderly omeprazole-treated patients (68%) healed and symptom-free was nearly three times that of elderly H2RA-treated patients (23%, p < 0.001). In the young patient group the proportion of omeprazole-treated patients (57%) both healed and symptom-free was nearly twice that of H2RA-treated patients (29%, p < 0.001). The advantage of omeprazole over H2RA, in terms of endoscopic healing and symptom relief, is at least as great in elderly patients as in younger patients. [ABSTRACT FROM AUTHOR]
- Published
- 1994
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21. Screening sinus CT scans in pediatric bone marrow transplant patients
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Billings, K. R., Lowe, L. H., Aquino, V. M., and Biavati, M. J.
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- 2000
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22. Cell-specific differences in O6-alkylguanine DNA repair activity during continuous exposure to carcinogen.
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Swenberg, J A, Bedell, M A, Billings, K C, Umbenhauer, D R, and Pegg, A E
- Abstract
The activity of the alkyl acceptor protein (AAP) responsible for repair of DNA containing the promutagenic lesion O6-alkylguanine was determined in hepatocytes and nonparenchymal cells (NPC) obtained from livers of control rats and rats exposed to hepatocarcinogens that primarily induce vascular or hepatocellular neoplasms. Basal levels of AAP activity were found to be 4-5 times higher in hepatocytes than in NPC. Exposure to 1,2-dimethylhydrazine or diethylnitrosamine produced a 2- to 3-fold enhancement of this activity in hepatocytes after exposure for as little as 3 days. The enhanced hepatocyte activity persisted throughout a 28-day exposure to 1,2-dimethylhydrazine. In contrast, AAP activity in NPC was decreased during the first week of exposure to 1,2-dimethylhydrazine and subsequently returned to control levels. No enhancement of AAP was apparent in the NPC. These and related data suggest that enhancement of this activity in rat hepatocytes is a response to cell proliferation. In contrast, the data clearly demonstrate that neither increased cell replication nor the presence of O6-alkylguanine was capable of enhancing AAP activity in NPC. Cellular differences in the repair of O6-alkylguanine appear to be a critical mechanism responsible for cell specificity in chemical carcinogenesis by alkylating agents.
- Published
- 1982
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23. Nicotinamide is an Endogenous Agonist for a C. elegans TRPV OSM-9 and OCR-4 Channel
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Upadhyay, A., Pisupati, A., Jegla, T., Crook, Matthew, Mickolajczyk, K. J., Shorey, M., Rohan, L. E., Billings, K. A., Rolls, M. M., Hancock, W. O., Hanna-Rose, W., Upadhyay, A., Pisupati, A., Jegla, T., Crook, Matthew, Mickolajczyk, K. J., Shorey, M., Rohan, L. E., Billings, K. A., Rolls, M. M., Hancock, W. O., and Hanna-Rose, W.
24. Geological map of the Cardigan quadrangle, New Hampshire
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FOWLER-BILLINGS, K., primary
- Published
- 1942
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25. Exploiting upper and lower bounds in top-down query optimization
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Shapiro, L., primary, Maier, D., additional, Benninghoff, P., additional, Billings, K., additional, Fan, Y., additional, Hatwal, K., additional, Wang, Q., additional, Zhang, Y., additional, Wu, H.-M., additional, and Vance, B., additional
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26. Response of fruit fly ( Drosophila pseudoobscura ) to diet manipulation of nutrient density.
- Author
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Novak TE, Billings K, Ellis SG, Smith MF, Wills BD, and Stevison LS
- Abstract
Caloric intake can greatly affect many aspects of an organism's life. A deficiency of calories can lead to stress resulting in decreased fecundity, insufficient calories to maintain tissues and increased lifespan. Conversely, increasing caloric density increases fecundity and decreases lifespan. Despite decades of work exploring food quality and quantity on physiology in the model species Drosophila melanogaster Meigan 1830 (Diptera: Drosophilidae) and the melanogaster group in general, relatively little work explores the physiological responses to diet manipulation in other Drosophila species, like the obscura species group. Here, we looked at the effects of five different caloric densities (0.5×, 0.75×, 1.0×, 1.5× and 3.0×) on food intake, body weight, body fat, fecundity and longevity in D. pseudoobscura Frolova & Astaurov, 1929 (Diptera: Drosophilidae). Comparing longevity and fecundity across diets, we found that heavy caloric concentration (3.0×) decreases lifespan and that calorie restriction (0.5× and 0.75×) led to significant decreases in fecundity and body weight. However, calorie concentration did not significantly increase D. pseudoobscura body fat. By expanding our understanding of the physiological responses to diet stress to D. pseudoobscura , we establish the framework for comparative work across Drosophila species. With this information, we can then identify which physiological responses to diet manipulation might be most conserved and comparable across species., Competing Interests: CONFLICT OF INTEREST STATEMENT The authors declare no conflicts of interest.
- Published
- 2024
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27. Perioperative opioids in high-risk children undergoing tonsillectomy - A single institution experience.
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Park AC, Billings K, Maddalozzo J, Dsida R, Benzon HA, Lavin J, and Hazkani I
- Subjects
- Humans, Male, Female, Child, Preschool, Retrospective Studies, Child, Infant, Sleep Apnea, Obstructive surgery, Perioperative Care methods, Adenoidectomy, Pain Management methods, Adolescent, Tonsillectomy, Analgesics, Opioid administration & dosage, Analgesics, Opioid therapeutic use, Pain, Postoperative drug therapy, Pain, Postoperative prevention & control, Pain, Postoperative etiology
- Abstract
Background: Patients undergoing tonsillectomy/ adenotonsillectomy (T/AT) can experience substantial postoperative pain. The aims of this study are to assess perioperative pain management in high-risk children (children with severe obstructive sleep apnea and other complex medical comorbidities or age younger than 2 years) undergoing T/AT, and the impact on oxygen levels and pain during extended Post-Anesthesia Care Unit (PACU) admission., Methods: A retrospective case series study at a tertiary care children's hospital., Results: There were 278 children enrolled in the study. The Apnea-Hypopnea index and mean oxygen nadir on preoperative polysomnography were 31.3 ± 25.76/h and 79.5 ± 9.5 % respectively. Overall, 246 (89 %) patients received intraoperative opioids alone (n = 35, 13 %) or in combination with non-opioid analgesia (n = 209, 75 %). While the median dose of opioid-free medications (acetaminophen, ibuprofen) ranged from 93 to 100 % of standard maximal dosing by weight and age, the median dose of opioids was significantly lower and ranged from 54 to 63 % of standard maximal dosing by weight and age, with 43 % of the patients receiving less than half the recommended maximum dose. Oxygen desaturation was charted in 21 patients (8 %) during their PACU admission. Patients who received opioid-free analgesia were as likely to develop oxygen desaturations (n = 17 (81 %) vs. n = 228 (89.4 %), p = 0.27) and to receive rescue pain medication during their PACU stay as patients who received opioids intraoperatively (n = 18 (56 %) vs. n = 167 (68 %), p = 0.23)., Conclusions: Intraoperative pain management varies across high-risk pediatric tonsillectomies. Opioid-free analgesia was not associated with an increased need for pain medications during PACU admission, or with a decreased likelihood of oxygen desaturations compared to intra-operative opioid analgesia use., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest and that this study did not receive financial support. All authors have seen and approved the manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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28. Characteristics of healthcare personnel with SARS-CoV-2 infection: 10 emerging infections program sites in the United States, April 2020-December 2021.
- Author
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Chea N, Eure T, Alkis Ramirez R, Zlotorzynska M, Blazek GT, Nadle J, Lee J, Czaja CA, Johnston H, Barter D, Kellogg M, Emanuel C, Meek J, Brackney M, Carswell S, Thomas S, Fridkin SK, Wilson LE, Perlmutter R, Marceaux-Galli K, Fell A, Lovett S, Lim S, Lynfield R, Shrum Davis S, Phipps EC, Sievers M, Dumyati G, Myers C, Hurley C, Licherdell E, Pierce R, Ocampo VLS, Hall EW, Wilson C, Adre C, Kirtz E, Markus TM, Billings K, Plumb ID, Abedi GR, James-Gist J, Magill SS, and Grigg CT
- Abstract
Background: Understanding characteristics of healthcare personnel (HCP) with SARS-CoV-2 infection supports the development and prioritization of interventions to protect this important workforce. We report detailed characteristics of HCP who tested positive for SARS-CoV-2 from April 20, 2020 through December 31, 2021., Methods: CDC collaborated with Emerging Infections Program sites in 10 states to interview HCP with SARS-CoV-2 infection (case-HCP) about their demographics, underlying medical conditions, healthcare roles, exposures, personal protective equipment (PPE) use, and COVID-19 vaccination status. We grouped case-HCP by healthcare role. To describe residential social vulnerability, we merged geocoded HCP residential addresses with CDC/ATSDR Social Vulnerability Index (SVI) values at the census tract level. We defined highest and lowest SVI quartiles as high and low social vulnerability, respectively., Results: Our analysis included 7,531 case-HCP. Most case-HCP with roles as certified nursing assistant (CNA) (444, 61.3%), medical assistant (252, 65.3%), or home healthcare worker (HHW) (225, 59.5%) reported their race and ethnicity as either non-Hispanic Black or Hispanic. More than one third of HHWs (166, 45.2%), CNAs (283, 41.7%), and medical assistants (138, 37.9%) reported a residential address in the high social vulnerability category. The proportion of case-HCP who reported using recommended PPE at all times when caring for patients with COVID-19 was lowest among HHWs compared with other roles., Conclusions: To mitigate SARS-CoV-2 infection risk in healthcare settings, infection prevention, and control interventions should be specific to HCP roles and educational backgrounds. Additional interventions are needed to address high social vulnerability among HHWs, CNAs, and medical assistants.
- Published
- 2024
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29. Long-term (180-Day) Outcomes in Critically Ill Patients With COVID-19 in the REMAP-CAP Randomized Clinical Trial.
- Author
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Higgins AM, Berry LR, Lorenzi E, Murthy S, McQuilten Z, Mouncey PR, Al-Beidh F, Annane D, Arabi YM, Beane A, van Bentum-Puijk W, Bhimani Z, Bonten MJM, Bradbury CA, Brunkhorst FM, Burrell A, Buzgau A, Buxton M, Charles WN, Cove M, Detry MA, Estcourt LJ, Fagbodun EO, Fitzgerald M, Girard TD, Goligher EC, Goossens H, Haniffa R, Hills T, Horvat CM, Huang DT, Ichihara N, Lamontagne F, Marshall JC, McAuley DF, McGlothlin A, McGuinness SP, McVerry BJ, Neal MD, Nichol AD, Parke RL, Parker JC, Parry-Billings K, Peters SEC, Reyes LF, Rowan KM, Saito H, Santos MS, Saunders CT, Serpa-Neto A, Seymour CW, Shankar-Hari M, Stronach LM, Turgeon AF, Turner AM, van de Veerdonk FL, Zarychanski R, Green C, Lewis RJ, Angus DC, McArthur CJ, Berry S, Derde LPG, Gordon AC, Webb SA, and Lawler PR
- Subjects
- Adult, Humans, Female, Middle Aged, Male, Lopinavir therapeutic use, Ritonavir therapeutic use, Follow-Up Studies, Hydroxychloroquine therapeutic use, SARS-CoV-2, Critical Illness therapy, Bayes Theorem, COVID-19 Serotherapy, Adrenal Cortex Hormones therapeutic use, Anticoagulants adverse effects, Receptors, Interleukin-6, COVID-19
- Abstract
Importance: The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown., Objective: To determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes., Design, Setting, and Participants: Prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022., Interventions: Patients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401)., Main Outcomes and Measures: The main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83., Results: Among 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06 [95% CrI, 0.82-1.38]) and the probabilities of harm from hydroxychloroquine (96.9%; HR, 1.51 [95% CrI, 0.98-2.29]) and the combination of lopinavir-ritonavir and hydroxychloroquine (96.8%; HR, 1.61 [95% CrI, 0.97-2.67]) were high. The corticosteroid domain was stopped early prior to reaching a predefined statistical trigger; there was a 57.1% to 61.6% probability of improving 6-month survival across varying hydrocortisone dosing strategies., Conclusions and Relevance: Among critically ill patients with COVID-19 randomized to receive 1 or more therapeutic interventions, treatment with an IL-6 receptor antagonist had a greater than 99.9% probability of improved 180-day mortality compared with patients randomized to the control, and treatment with an antiplatelet had a 95.0% probability of improved 180-day mortality compared with patients randomized to the control. Overall, when considered with previously reported short-term results, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months.
- Published
- 2023
- Full Text
- View/download PDF
30. Testing Abiotic Reduction of NAD + Directly Mediated by Iron/Sulfur Minerals.
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Weber JM, Henderson BL, LaRowe DE, Goldman AD, Perl SM, Billings K, and Barge LM
- Subjects
- Minerals, Oxidation-Reduction, Sulfur, Iron metabolism, NAD chemistry, NAD metabolism
- Abstract
Life emerged in a geochemical context, possibly in the midst of mineral substrates. However, it is not known to what extent minerals and dissolved inorganic ions could have facilitated the evolution of biochemical reactions. Herein, we have experimentally shown that iron sulfide minerals can act as electron transfer agents for the reduction of the ubiquitous biological protein cofactor nicotinamide adenine dinucleotide (NAD
+ ) under anaerobic prebiotic conditions, observing the NAD+ /NADH redox transition by using ultraviolet-visible spectroscopy and1 H nuclear magnetic resonance. This reaction was mediated with iron sulfide minerals, which were likely abundant on early Earth in seafloor and hydrothermal settings; and the NAD+ /NADH redox reaction occurred in the absence of UV light, peptide ligand(s), or dissolved mediators. To better understand this reaction, thermodynamic modeling was also performed. The ability of an iron sulfide mineral to transfer electrons to a biochemical cofactor that is found in every living cell demonstrates how geologic materials could have played a direct role in the evolution of certain cofactor-driven metabolic pathways.- Published
- 2022
- Full Text
- View/download PDF
31. Reduction in Pediatric Ambulatory Adenotonsillectomy Length of Stay Using Clinical Care Guidelines.
- Author
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Lavin J, Studer A, Thompson D, Ida J, Rastatter J, Manisha P, Huetteman P, Hoeman E, Duggan S, Birmingham P, King MR, and Billings K
- Subjects
- Adenoidectomy standards, Adolescent, Ambulatory Surgical Procedures standards, Child, Child, Preschool, Female, Humans, Infant, Length of Stay statistics & numerical data, Length of Stay trends, Male, Patient Discharge standards, Retrospective Studies, Tonsillectomy standards, Adenoidectomy statistics & numerical data, Ambulatory Surgical Procedures statistics & numerical data, Postoperative Care standards, Practice Guidelines as Topic, Tonsillectomy statistics & numerical data
- Abstract
Objective: Standardization of postoperative care using clinical care guidelines (CCG) improves quality by minimizing unwarranted variation. It is unknown whether CCGs impact patient throughput in outpatient adenotonsillectomy (T&A). We hypothesize that CCG implementation is associated with decreased postoperative length of stay (LOS) in outpatient T&A., Methods: A multidisciplinary team was assembled to design and implement a T&A CCG. Standardized discharge criteria were established, including goal fluid intake and parental demonstration of medication administration. An order set was created that included a hard stop for discharge timeframe with choices "meets criteria," "4-hour observation," and "overnight stay." Consensus was achieved in June 2018, and the CCG was implemented in October 2018. Postoperative LOS for patients discharged the same day was tracked using control chart analysis with standard definitions for centerline shift being utilized. Trends in discharge timeframe selection were also followed., Results: Between July 2015 and August 2017, the average LOS was 4.82 hours. This decreased to 4.39 hours in September 2017 despite no known interventions and remained stable for 17 months. After CCG implementation, an initial trend toward increased LOS was followed by centerline shifts to 3.83 and 3.53 hours in March and October 2019, respectively. Selection of the "meets criteria" discharge timeframe increased over time after CCG implementation (R
2 = 0.38 P = .003)., Conclusions: Implementation of a CCG with standardized discharge criteria was associated with shortened postoperative LOS in outpatient T&A. Concurrently, surgeons shifted practice to discharge patients upon meeting criteria rather than after a designated timeframe., Level of Evidence: NA Laryngoscope, 131:2610-2615, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)- Published
- 2021
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32. Standardized Order Set Exhibits Surgeon Adherence to Pain Protocol in Pediatric Adenotonsillectomy.
- Author
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Studer A, Billings K, Thompson D, Ida J, Rastatter J, Patel M, Huetteman P, Hoeman E, Duggan S, Mudahar S, Birmingham P, King M, and Lavin J
- Subjects
- Adenoidectomy adverse effects, Adolescent, Analgesics, Opioid adverse effects, Child, Child, Preschool, Drug Prescriptions standards, Drug Prescriptions statistics & numerical data, Electronic Health Records organization & administration, Electronic Health Records standards, Emergency Service, Hospital statistics & numerical data, Female, Hospitals, Pediatric organization & administration, Hospitals, Pediatric standards, Humans, Infant, Infant, Newborn, Male, Pain Management adverse effects, Pain Management statistics & numerical data, Pain, Postoperative etiology, Patient Discharge standards, Patient Discharge statistics & numerical data, Patient Readmission statistics & numerical data, Practice Patterns, Physicians' standards, Prospective Studies, Surgeons standards, Surgeons statistics & numerical data, Tertiary Care Centers organization & administration, Tertiary Care Centers standards, Tonsillectomy adverse effects, Clinical Protocols standards, Pain Management standards, Pain, Postoperative drug therapy, Practice Patterns, Physicians' organization & administration, Quality Improvement
- Abstract
Objectives/hypothesis: To produce a sustained reduction in opioid prescriptions in patients <5 years of age undergoing T&A through utilization of standardized algorithms and electronic health record (EHR) automation tools., Study Design: Prospective quality improvement initiative., Methods: Plan-do-study-act (PDSA) methodology was used to design an age-based postoperative pain regimen in which children <5 years of age received a non-opioid pain regimen, and option to prescribe oxycodone for additional pain relief was given for children >5 years of age. Standardized discharge instructions and automated, age-specific order sets were created to facilitate adherence. Rate of discharge opioid prescription was monitored and balanced against post-discharge opioid prescriptions and returns to the emergency department (ED)., Results: In children <5 years of age undergoing T&A, reduction in opioid prescription rates from 65.9% to 30.9% after initial implementation of the order set was noted. Ultimately, reduction of opioid prescribing rates to 3.7% of patients was noted after pain-regimen consensus and EHR order set implementation. Opioid prescriptions in patients >5 years of age decreased from 90.6% to 58.1% initially, and then down 35.9% by the last time point analyzed. Requests for outpatient opioid prescriptions did not increase. There was no significant change in returns to the emergency ED for pain management, or in the number opioids prescribed when patients returned to the ED., Conclusions: Iterative cycles of improvement utilizing standardized pain management algorithms and EHR tools were effective means of producing a sustained reduction in opioid prescriptions in postoperative T&A patients. Such findings suggest a framework for similar interventions in other pediatric otolaryngology settings., Level of Evidence: 4 Laryngoscope, 131:E2337-E2343, 2021., (© 2020 American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA).)
- Published
- 2021
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33. Factors That Might Affect SARS-CoV-2 Transmission Among Foreign-Born and U.S.-Born Poultry Facility Workers - Maryland, May 2020.
- Author
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Rubenstein BL, Campbell S, Meyers AR, Crum DA, Mitchell CS, Hutson J, Williams DL, Senesie SS, Gilani Z, Reynolds S, Alba B, Tavitian S, Billings K, Saintus L, Martin SB Jr, and Mainzer H
- Subjects
- Adult, Animals, COVID-19 epidemiology, Female, Humans, Male, Maryland epidemiology, Middle Aged, Poultry, Risk Factors, COVID-19 transmission, Emigrants and Immigrants statistics & numerical data, Food-Processing Industry, Occupational Diseases epidemiology
- Abstract
Numerous recent assessments indicate that meat and poultry processing facility workers are at increased risk for infection with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1-4). Physical proximity to other workers and shared equipment can facilitate disease transmission in these settings (2-4). The disproportionate number of foreign-born workers employed in meat and poultry processing reflects structural, social, and economic inequities that likely contribute to an increased COVID-19 incidence in this population* (5). In May 2020, the Maryland Department of Health and CDC investigated factors that might affect person-to-person SARS-CoV-2 transmission among persons who worked at two poultry processing facilities.
† A survey administered to 359 workers identified differences in risk factors for SARS-CoV-2 infection between workers born outside the United States and U.S.-born workers. Compared with U.S.-born workers, foreign-born workers had higher odds of working in fixed locations on the production floor (odds ratio [OR] for cutup and packaging jobs = 4.8), of having shared commutes (OR = 1.9), and of living with other poultry workers (OR = 6.0). They had lower odds of participating in social gatherings (OR for visits to family = 0.2; OR for visits to friends = 0.4), and they visited fewer businesses in the week before the survey than did their U.S.-born coworkers. Some workplace risk factors can be mitigated through engineering and administrative controls focused on the production floor, and this will be of particular benefit to the foreign-born workers concentrated in these areas. Employers and health departments can also partner with local organizations to disseminate culturally and linguistically tailored messages about risk reduction behaviors in community settings, including shared transportation§ and household members dwelling in close quarters.¶ ., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.- Published
- 2020
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34. Multifunctional Building Blocks Compatible with Photoredox-Mediated Alkylation for DNA-Encoded Library Synthesis.
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Badir SO, Sim J, Billings K, Csakai A, Zhang X, Dong W, and Molander GA
- Subjects
- Alkylation, Amines chemistry, Molecular Structure, Oxidation-Reduction, Photochemical Processes, Stereoisomerism, Amines chemical synthesis, DNA chemistry, Hydrocarbons, Brominated chemistry
- Abstract
DNA-encoded library (DEL) technology has emerged as a novel interrogation modality for ligand discovery in the pharmaceutical industry. Given the increasing demand for a higher proportion of C(sp
3 )-hybridized centers in DEL platforms, a photoredox-mediated cross-coupling and defluorinative alkylation process is introduced using commercially available alkyl bromides and structurally diverse α-silylamines. Notably, no protecting group strategies for amines are necessary for the incorporation of a variety of amino-acid-based organosilanes, providing crucial branching points for further derivatization.- Published
- 2020
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35. Open-Air Alkylation Reactions in Photoredox-Catalyzed DNA-Encoded Library Synthesis.
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Phelan JP, Lang SB, Sim J, Berritt S, Peat AJ, Billings K, Fan L, and Molander GA
- Subjects
- Air, Alkylation, Catalysis, Molecular Structure, Oxidation-Reduction, DNA chemistry, Nickel chemistry, Photochemical Processes, Small Molecule Libraries
- Abstract
DNA-encoded library (DEL) technology is a powerful tool commonly used by the pharmaceutical industry for the identification of compounds with affinity to biomolecular targets. Success in this endeavor lies in sampling diverse chemical libraries. However, current DELs tend to be deficient in C(sp
3 ) carbon counts. We report unique solutions to the challenge of increasing both the chemical diversity of these libraries and their C(sp3 ) carbon counts by merging Ni/photoredox dual catalytic C(sp2 )-C(sp3 ) cross-coupling as well as photoredox-catalyzed radical/polar crossover alkylation protocols with DELs. The successful integration of multiple classes of radical sources enables the rapid incorporation of a diverse set of alkyl fragments.- Published
- 2019
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36. Geoelectrodes and Fuel Cells for Simulating Hydrothermal Vent Environments.
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Barge LM, Krause FC, Jones JP, Billings K, and Sobron P
- Subjects
- Carbon chemistry, Catalysis, Electrochemistry, Electrodes, Glass chemistry, Hydrogen analysis, Membranes, Artificial, Oxidation-Reduction, Oxygen analysis, Polymers chemistry, Spectrum Analysis, Raman, Sulfides chemistry, Energy-Generating Resources, Hydrothermal Vents
- Abstract
Gradients generated in hydrothermal systems provide a significant source of free energy for chemosynthetic life and may play a role in present-day habitability on ocean worlds. Electron/proton/ion gradients, particularly in the context of hydrothermal chimney structures, may also be relevant to the origins of life on Earth. Hydrothermal vents are similar in some ways to typical fuel cell devices: redox/pH gradients between seawater and hydrothermal fluid are analogous to the fuel cell oxidant and fuel reservoirs; the porous chimney wall is analogous to a separator or ion-exchange membrane and is also a conductive path for electrons; and the hydrothermal minerals are analogous to electrode catalysts. The modular and scalable characteristics of fuel cell systems make for a convenient planetary geology test bed in which geologically relevant components may be assembled and investigated in a controlled simulation environment. We have performed fuel cell experiments and electrochemical studies to better understand the catalytic potential of seafloor minerals and vent chimneys, using samples from a black smoker vent chimney as an initial demonstration. In a fuel cell with Na
+ -conducting Nafion® membranes and liquid fuel/oxidant reservoirs (simulating the vent environment), the black smoker mineral catalyst in the membrane electrode assembly was effective in reducing O2 and oxidizing sulfide. In a H2 /O2 polymer electrolyte membrane (PEM) fuel cell with H+ -conducting Nafion membranes, the black smoker catalyst was effective in reducing O2 but not in oxidizing H2 . These fuel cell experiments accurately simulated the redox reactions that could occur in a geological setting with this particular catalyst, and also tested whether the minerals are sufficiently active to replace a commercial fuel cell catalyst. Similar experiments with other geocatalysts could be utilized to test which redox reactions could be driven in other hydrothermal systems, including hypothesized vent systems on other worlds.- Published
- 2018
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37. Insulin signaling displayed a differential tissue-specific response to low-dose dihydrotestosterone in female mice.
- Author
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Andrisse S, Billings K, Xue P, and Wu S
- Subjects
- Animals, Dose-Response Relationship, Drug, Energy Metabolism drug effects, Female, Hyperandrogenism genetics, Hyperandrogenism metabolism, Hyperandrogenism pathology, Insulin Resistance genetics, Mice, Mice, Inbred C57BL, Muscle, Skeletal drug effects, Muscle, Skeletal metabolism, Organ Specificity drug effects, Organ Specificity genetics, Ovary drug effects, Ovary metabolism, Signal Transduction drug effects, Signal Transduction genetics, Dihydrotestosterone pharmacology, Insulin metabolism
- Abstract
Hyperandrogenemia and hyperinsulinemia are believed to play prominent roles in polycystic ovarian syndrome (PCOS). We explored the effects of low-dose dihydrotestosterone (DHT), a model of PCOS, on insulin signaling in metabolic and reproductive tissues in a female mouse model. Insulin resistance in the energy storage tissues is associated with type 2 diabetes. Insulin signaling in the ovaries and pituitary either directly or indirectly stimulates androgen production. Energy storage and reproductive tissues were isolated and molecular assays were performed. Livers and white adipose tissue (WAT) from DHT mice displayed lower mRNA and protein expression of insulin signaling intermediates. However, ovaries and pituitaries of DHT mice exhibited higher expression levels of insulin signaling genes/proteins. Insulin-stimulated p-AKT levels were blunted in the livers and WAT of the DHT mice but increased or remained the same in the ovaries and pituitaries compared with controls. Glucose uptake decreased in liver and WAT but was unchanged in pituitary and ovary of DHT mice. Plasma membrane GLUTs were decreased in liver and WAT but increased in ovary and pituitary of DHT mice. Skeletal muscle insulin-signaling genes were not lowered in DHT mice compared with control. DHT mice did not display skeletal muscle insulin resistance. Insulin-stimulated glucose transport increased in skeletal muscles of DHT mice compared with controls. DHT mice were hyperinsulinemic. However, the differential mRNA and protein expression pattern was independent of hyperinsulinemia in cultured hepatocytes and pituitary cells. These findings demonstrate a differential effect of DHT on the insulin-signaling pathway in energy storage vs. reproductive tissues independent of hyperinsulinemia.
- Published
- 2018
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38. Low-Dose Dihydrotestosterone Drives Metabolic Dysfunction via Cytosolic and Nuclear Hepatic Androgen Receptor Mechanisms.
- Author
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Andrisse S, Childress S, Ma Y, Billings K, Chen Y, Xue P, Stewart A, Sonko ML, Wolfe A, and Wu S
- Subjects
- Animals, Class Ia Phosphatidylinositol 3-Kinase metabolism, Cyclic AMP Response Element-Binding Protein genetics, Dihydrotestosterone blood, Female, Forkhead Box Protein O1 metabolism, Gluconeogenesis, Hepatocytes metabolism, Hyperandrogenism metabolism, Insulin Resistance, Liver metabolism, Mice, Inbred C57BL, Promoter Regions, Genetic, Receptors, Androgen metabolism, Anovulation etiology, Dihydrotestosterone administration & dosage, Disease Models, Animal, Glucose Metabolism Disorders etiology, Hyperandrogenism complications
- Abstract
Androgen excess in women is associated with metabolic dysfunction (e.g., obesity, hyperinsulinemia, insulin resistance, and increased risk of type 2 diabetes) and reproductive dysfunction (e.g., polycystic ovaries, amenorrhea, dysregulated gonadotropin release, and infertility). We sought to identify the effects of androgen excess on glucose metabolic dysfunction and the specific mechanisms of action by which androgens are inducing pathology. We developed a mouse model that displayed pathophysiological serum androgen levels with normal body mass/composition to ensure that the phenotypes were directly from androgens and not an indirect consequence of obesity. We performed reproductive tests, metabolic tests, and hormonal assays. Livers were isolated and examined via molecular, biochemical, and histological analysis. Additionally, a low-dose dihydrotestosterone (DHT) cell model using H2.35 mouse hepatocytes was developed to study androgen effects on hepatic insulin signaling. DHT mice demonstrated impaired estrous cyclicity; few corpora lutea in the ovaries; glucose, insulin, and pyruvate intolerance; and lowered hepatic insulin action. Mechanistically, DHT increased hepatic androgen-receptor binding to phosphoinositide-3-kinase (PI3K)-p85, resulting in dissociation of PI3K-p85 from PI3K-p110, leading to reduced PI3K activity and decreased p-AKT and, thus, lowered insulin action. DHT increased gluconeogenesis via direct transcriptional regulation of gluconeogenic enzymes and coactivators. The hepatocyte model recapitulated the in vivo findings. The DHT-induced hepatocyte insulin resistance was reversed by the androgen-receptor antagonist, flutamide. These findings present a phenotype (i.e., impaired glucose tolerance and disrupted glucose metabolism) in a lean hyperandrogenemia model (low-dose DHT) and data to support 2 molecular mechanisms that help drive androgen-induced impaired glucose metabolism., (Copyright © 2017 by the Endocrine Society.)
- Published
- 2017
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39. Postoperative pain relief in infants undergoing myringotomy and tube placement: comparison of a novel regional anesthetic block to intranasal fentanyl--a pilot analysis.
- Author
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Voronov P, Tobin MJ, Billings K, Coté CJ, Iyer A, and Suresh S
- Subjects
- Analgesics, Opioid administration & dosage, Double-Blind Method, Female, Fentanyl administration & dosage, Humans, Infant, Length of Stay, Male, Pain Measurement drug effects, Pilot Projects, Postoperative Nausea and Vomiting epidemiology, Prospective Studies, Vagus Nerve, Analgesics, Opioid therapeutic use, Anesthesia, Conduction, Fentanyl therapeutic use, Middle Ear Ventilation, Nerve Block, Pain, Postoperative drug therapy
- Abstract
Aim: The aim of this study was to investigate the use of a novel regional anesthetic technique for the management of pain in the postoperative period in infants and children undergoing myringotomy and tube placement., Methods: After institutional review board (IRB) approval was obtained, 200 children were randomized in this double blind, prospective, randomized controlled trial to receive either a nerve block of the auricular branch of the Vagus (Nerve of Arnold) with 0.2 ml of 0.25% bupivacaine or receive intranasal fentanyl 2 mcg.kg(-1) after induction of general anesthesia. Patients were monitored in the recovery room for analgesia, need for additional analgesia, incidence of nausea and vomiting, and time to discharge from the hospital. Additional analgesics administered in the PACU, surgical short-stay unit as well as at home were also recorded., Results: There was no difference in the pain scores between groups (P = 0.53); there was no difference in the amount of rescue medications between groups (P = 0.86); there was no difference in the incidence of nausea and vomiting between groups (P = 0.34); there was no difference in the time to discharge between groups (P = 0.5)., Conclusions: This pilot study demonstrates the efficacy of a peripheral nerve block for management of postoperative pain in infants and children undergoing myringotomy and tube placement. This may be a viable alternative for postoperative pain control in this population. Future multi-center, randomized controlled trials may be necessary to validate the efficacy of this block in infants and children.
- Published
- 2008
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40. Congenital foregut duplication cysts of the anterior tongue.
- Author
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Eaton D, Billings K, Timmons C, Booth T, and Biavati JM
- Subjects
- Choristoma diagnosis, Choristoma surgery, Cysts diagnosis, Cysts surgery, Female, Humans, Infant, Infant, Newborn, Male, Retrospective Studies, Tongue Diseases diagnosis, Tongue Diseases surgery, Choristoma congenital, Cysts congenital, Intestinal Mucosa, Tongue Diseases congenital
- Abstract
Objective: To review our experience with foregut duplication cysts of the anterior tongue, an unusual and rarely encountered mass in this location., Design: A retrospective review of patients with anterior tongue foregut duplication cysts identified between 1990 and 2000., Setting: Academic, tertiary care children's medical center., Patients: Six pediatric patients (5 boys and 1 girl) ranging in age from birth to 8 months at diagnosis., Intervention: Three patients underwent preoperative magnetic resonance imaging (MRI). All 6 patients underwent excisional biopsy., Main Outcome Measures: Clinical description of foregut duplication cysts, ability to make the diagnosis preoperatively, and recurrence rates., Results: No patient presented with respiratory compromise, despite the large size of the anterior tongue masses (range, 1.5-2.4 cm). An MRI study was performed in 3 patients, all given a presumptive diagnosis of dermoid cyst based on the radiographic findings. No patient was diagnosed correctly prior to surgical excision. All patients underwent surgical excision, and the average time from birth to surgical excision was 11 months (range, 3 days to 3.7 years). Surgical pathologic findings were reported as a foregut duplication cyst (enterocystoma) in all patients, with 3 specimens containing foci of gastric mucosa. No recurrence has occurred at 1-month follow-up., Conclusions: Foregut duplication cysts rarely present in the anterior tongue and are easily misdiagnosed preoperatively. An MRI study is helpful in preoperative planning, although all lesions were radiologically indistinguishable from dermoid cysts. These masses may be an underappreciated entity in the differential diagnosis of congenital anterior tongue masses.
- Published
- 2001
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41. Infected neonatal cervical thymic cyst.
- Author
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Billings KR, Rollins NK, Timmons C, and Biavati MJ
- Subjects
- Haemophilus Infections complications, Haemophilus influenzae, Humans, Infant, Newborn, Male, Mediastinal Cyst microbiology, Mediastinal Cyst pathology, Pneumococcal Infections complications, Airway Obstruction etiology, Mediastinal Cyst complications
- Published
- 2000
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42. Hemangiopericytoma of the head and neck.
- Author
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Billings KR, Fu YS, Calcaterra TC, and Sercarz JA
- Subjects
- Adolescent, Adult, Aged, Biopsy, Needle, Child, Combined Modality Therapy, Head and Neck Neoplasms diagnosis, Head and Neck Neoplasms mortality, Head and Neck Neoplasms therapy, Hemangiopericytoma diagnosis, Hemangiopericytoma mortality, Hemangiopericytoma secondary, Hemangiopericytoma therapy, Humans, Immunohistochemistry, Male, Middle Aged, Prognosis, Registries, Retrospective Studies, Survival Rate, Head and Neck Neoplasms pathology, Hemangiopericytoma pathology
- Abstract
Purpose: To report a series of patients with hemangiopericytoma (HP) of the head and neck, to review pathological features of these tumors, and to discuss management options., Materials and Methods: A retrospective review of the medical records at the University of California, Los Angeles (UCLA) Medical Center in Los Angeles, CA, was done in order to identify those patients with primary HP of the head and neck, including soft tissue and mucosal sites., Results: Ten patients with HP of the head and neck were identified. There was an equal sex distribution and an average age of 36 (range 10-65). Seven of the tumors arose from soft tissue sites in the head and neck, and the remaining 3 arose from the mucosa. All patients underwent wide excision of the primary lesion with a local recurrence rate of 40%. Thirty percent of patients developed metastatic lung disease 0 to 8 years after initial diagnosis. Each patient who developed metastatic disease had abundant mitoses on pathological review compared with rare or absent mitoses in the lesions that took a more benign course., Conclusions: Pathological appearance of resected HP is predictive of later metastatic potential. Long-term follow-up is necessary in patients even after radical resection because recurrence or metastasis may be delayed by many years.
- Published
- 2000
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43. Respiratory difficulty following bismuth subgallate aspiration.
- Author
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Murray AD, Gibbs SR, Billings KR, and Biavati MJ
- Subjects
- Adenoidectomy, Child, Female, Gallic Acid adverse effects, Humans, Infant, Tonsillectomy, Gallic Acid analogs & derivatives, Hemostatics adverse effects, Inhalation, Organometallic Compounds adverse effects, Postoperative Complications, Respiratory Insufficiency etiology
- Abstract
Bismuth subgallate, an agent that initiates clotting via activation of factor XII, has been advocated for use in controlling bleeding during tonsillectomy and adenoidectomy. Direct aspiration of bismuth has produced pulmonary complications in laboratory animals, but no clinical correlation in humans has been previously described. We report 2 cases of bismuth aspiration that resulted in respiratory difficulty after tonsillectomy and adenoidectomy. Neither child's respiratory compromise required airway intubation. This report of pulmonary complications secondary to bismuth aspiration should alert surgeons to the potential for airway problems when using bismuth as a hemostatic agent for tonsillectomy and adenoidectomy.
- Published
- 2000
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44. Behavioral sensitization following repeated intravenous nicotine administration: gender differences and gonadal hormones.
- Author
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Booze RM, Welch MA, Wood ML, Billings KA, Apple SR, and Mactutus CF
- Subjects
- Animals, Body Weight drug effects, Estrus drug effects, Female, Ganglionic Stimulants pharmacokinetics, Injections, Intravenous, Male, Motor Activity drug effects, Nicotine pharmacokinetics, Nicotinic Agonists pharmacology, Ovariectomy, Rats, Rats, Sprague-Dawley, Time Factors, Vagina cytology, Ganglionic Stimulants pharmacology, Gonadal Steroid Hormones metabolism, Nicotine pharmacology, Sex Characteristics
- Abstract
Repeated intermittent administration of stimulants is well known to produce behavioral sensitization in male animals. The present studies explored whether 1) behavioral sensitization occurred with the i.v. route of administration, 2) sensitization was greater in females than in males, 3) sensitization was modulated by gonadectomy, 4) intact adult female rats maintained normal estrous cytology patterns in response to repeated nicotine administration, and 5) the pharmacokinetics of i.v. nicotine dosing. Adult male, female, castrated, and ovariectomized Sprague-Dawley rats (n = 48) were surgically implanted with an intravenous access port. Animals received 50 microg/kg i.v. nicotine once/day for 14 days. Immediately after the initial nicotine injection and the final day 14 nicotine injection, animals were placed in IR photocell activity chambers for 60 min. Observational time sampling of behavior was also simultaneously performed by an observer blind to treatment condition. An increase in behavioral activity of greater than 120% occurred across the 14-day time course of i.v. nicotine injections. The magnitude of the increase, however, varied as a function of component of activity, gender, and gonadectomy. The behavioral observation data further suggested that the females demonstrated an increased sensitivity to repeated nicotine, as evidenced in a more rapid response, for example, grooming. These behavioral observations were associated with peak arterial levels of nicotine (approximately 25 ng/ml) no greater than the average venous levels of nicotine commonly maintained by cigarette smokers. Repeated i.v. nicotine, at a dose of 50 microg/kg, did not interfere with intact female vaginal cytology or body weight; the failure to detect such alterations were not due to inadequate statistical power. Moreover, no nicotine-treated animals displayed persistent vaginal estrous or were acyclic. Collectively, these data suggest that the i.v. nicotine model may be particularly useful in exploring the gender-dependent effects of nicotine.
- Published
- 1999
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45. Causes of pediatric sensorineural hearing loss: yesterday and today.
- Author
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Billings KR and Kenna MA
- Subjects
- Adolescent, Child, Child, Preschool, Female, Hearing Loss, Sensorineural genetics, Humans, Infant, Infant, Newborn, Male, Retrospective Studies, Hearing Loss, Sensorineural etiology
- Abstract
Objective: To ascertain the present common causes of sensorineural hearing loss (SNHL) in children and compare them with those of previous reports., Design: A retrospective review of the medical records for all children with a diagnosis of SNHL seen from January 1, 1993, through September 30, 1996, at our institution., Setting: A tertiary care children's hospital., Patients: Three hundred one children, aged 1 week through 18 years, who presented for evaluation of SNHL., Results: Of the 301 children, 68.1% had a definite or probable cause of their SNHL identified; 18.9%, 1 or more possible causes; and 31.9%, no obvious cause. A family history of SNHL or prematurity and/or complicated perinatal course was found in 28.6% of patients. Named syndromes, multiple congenital anomalies, meningitis, or prenatal maternal factors, including maternal prenatal substance abuse, were present in another 38.5%. However, syndromes commonly reported to be associated with SNHL, such as Waardenburg syndrome, were seen in less than 1% of patients. The average age at diagnosis was 3.02 years for the bilateral moderate or worse SNHL; for unilateral SNHL, the average age was 3.97 years. The most useful diagnostic study was computed tomographic scanning., Conclusions: Sensorineural hearing loss is fairly common in children. Extensive workups, often without clear direction, should be reconsidered based on the children with SNHL who otolaryngologists are now seeing. Infant screening programs, although identifying many children earlier, will also provide the opportunity to fine-tune the evaluation (ie, cytomegalovirus titers and/or cultures at birth), increasing the diagnostic yield.
- Published
- 1999
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46. Inhibition of cell proliferation in head and neck squamous cell carcinoma cell lines with antisense cyclin D1.
- Author
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Wang MB, Billings KR, Venkatesan N, Hall FL, and Srivatsan ES
- Subjects
- Adult, Aged, Blotting, Southern, Blotting, Western, Cell Division physiology, DNA, Neoplasm analysis, Female, Humans, Male, Middle Aged, Neoplasm Staging, Polymerase Chain Reaction, Tumor Cells, Cultured, Carcinoma, Squamous Cell pathology, Cyclin D1 metabolism, Head and Neck Neoplasms pathology
- Abstract
Cyclin D1 and cyclin G are essential regulatory factors in the progression of the cell cycle from G0 through G1 and S phase. Aberrations in expression of these cyclins may lead to dysregulated cellular proliferation that could result in neoplasia. Amplification and overexpression of cyclin D1 have been observed in many human cancers, whereas cyclin G is a new cyclin recently described in osteosarcoma cells. This study was performed to determine whether these cyclins were amplified in head and neck squamous cell carcinoma (HNSCC) tumors. Polymerase chain reaction of DNA extracted from 22 HNSCC primary tumors and three HNSCC cell lines did not reveal amplification of cyclin D1 in any of the tumor samples. Southern blot analysis identified amplification of cyclin D1 in a single tumor. Amplification of cyclin G was not observed in any of the tumors by Southern blot hybridization with a cyclin G probe. HNSCC cell lines transfected with antisense cyclin D1 were tested for cell proliferation by the incorporation of 3H-thymidine into cells grown in serum-free media. By 72 hours of incubation, there was a greater than 30% reduction in proliferation of cells transfected with antisense cyclin D1 as compared with non-transfected control cells. The results indicate that cyclin D1 may play an important role in the growth and proliferation of HNSCC cells.
- Published
- 1998
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47. Deletion analysis of the p16/CDKN2 gene in head and neck squamous cell carcinoma using quantitative polymerase chain reaction method.
- Author
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Rawnsley JD, Srivatsan ES, Chakrabarti R, Billings KR, and Wang MB
- Subjects
- Chromosomes, Human, Pair 8, Chromosomes, Human, Pair 9, Cyclin-Dependent Kinase Inhibitor p16, DNA Primers, DNA, Neoplasm analysis, Fluorescent Dyes, Humans, Polymerase Chain Reaction, Carcinoma, Squamous Cell genetics, Carrier Proteins genetics, Gene Deletion, Genes, Tumor Suppressor genetics, Head and Neck Neoplasms genetics
- Abstract
Background: Recently, the p16/CDKN2/MTS1 gene in the 9p21-22 region has been offered as a candidate tumor suppressor gene. We examined the frequency of hemizygous and homozygous deletions of p16/CDKN2 in head and neck squamous cell carcinoma (HNSCC) using a quantitative polymerase chain reaction (PCR) method., Design: Twenty-one HNSCC and 12 corresponding normal DNA samples were examined for deletion of p16/ CDKN2 using PCR amplification and fluorescent quantification of DNA. All tumor and normal DNA samples were also amplified with fluorescein-labeled primers for a control DNA marker on chromosome 8p (D8S265). The ratios of the observed fluorescence of the p16/CDKN2 and 8p PCR products were compared., Setting and Participants: Patients with HNSCC scheduled to undergo surgical resection of their tumors were recruited. After the specimen was removed, a portion of the tissue was snap frozen for further DNA extraction., Results: Eight tumors (38%) had p16/CDKN2-D8S265 ratios of greater than 0.75; 8 tumors (38%), from 0.25 to 0.75; and 5 tumors (24%), of less than 0.25, the average ratio in this last group being 0.06., Conclusions: These ratios suggest a higher rate of homozygous deletion than previously reported and significant probable hemizygous deletion of the p16/CDKN2 gene in HNSCC.
- Published
- 1997
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48. Laryngotracheal stenosis in a case of Pena-Shokier syndrome.
- Author
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Billings KR, Kerner MM, Padbury JF, and Abemayor E
- Subjects
- Arthrogryposis complications, Brain abnormalities, Clubfoot complications, Constriction, Pathologic, Face abnormalities, Humans, Infant, Newborn, Lung abnormalities, Male, Syndrome, Abnormalities, Multiple, Laryngeal Diseases complications, Tracheal Diseases complications
- Published
- 1997
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49. Suppressive factor or factors derived from head and neck squamous cell carcinoma induce apoptosis in activated lymphocytes.
- Author
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Billings KR, Wang MB, and Lichtenstein AK
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Squamous Cell pathology, Cell Division, Cell Membrane drug effects, Cell Membrane ultrastructure, Cell Nucleus drug effects, Cell Nucleus ultrastructure, Culture Media, Conditioned pharmacology, DNA Fragmentation, DNA, Neoplasm analysis, Electrophoresis, Agar Gel, Female, Head and Neck Neoplasms pathology, Humans, Immunosuppressive Agents isolation & purification, Jurkat Cells drug effects, Jurkat Cells pathology, Laryngeal Neoplasms pathology, Male, Middle Aged, Mouth Neoplasms pathology, Pharyngeal Neoplasms pathology, Phytohemagglutinins pharmacology, T-Lymphocytes pathology, Tumor Cells, Cultured, Apoptosis drug effects, Carcinoma, Squamous Cell metabolism, Head and Neck Neoplasms metabolism, Immunosuppressive Agents pharmacology, Lymphocyte Activation drug effects, T-Lymphocytes drug effects
- Abstract
Our laboratory has previously identified a soluble factor derived from head and neck squamous cell carcinoma that impairs lymphocyte proliferative responses in vitro. This study further investigates the nature of the interaction between these factors and T lymphocytes. The proliferative activity of phytohemagglutinin-stimulated peripheral blood lymphocytes and the Jurkat T-cell line was significantly suppressed (>50%) by the supernatants of 13 (41.9%) of 31 recently explanted head and neck squamous cell carcinoma samples. A characteristic morphologic appearance of these suppressed cells and ladderlike pattern of DNA fragmentation on gel electrophoresis indicated that the suppressive supernatants were inducing or predisposing T cells to apoptotic death. This apoptosis-inducing activity may be similar to that previously described in a suppressive supernatant obtained from an esophageal carcinoma cell line. These results shed further light on the mechanism behind a soluble immunosuppressive factor or factors produced by head and neck squamous cell carcinoma.
- Published
- 1997
- Full Text
- View/download PDF
50. Internal jugular vein thrombosis.
- Author
-
Duffey DC, Billings KR, Eichel BS, and Sercarz JA
- Subjects
- Ampicillin administration & dosage, Ampicillin therapeutic use, Anti-Bacterial Agents administration & dosage, Anti-Bacterial Agents therapeutic use, Female, Humans, Injections, Intravenous, Jugular Veins diagnostic imaging, Middle Aged, Thrombophlebitis diagnosis, Thrombophlebitis drug therapy, Tomography, X-Ray Computed, Jugular Veins physiopathology, Thrombophlebitis physiopathology
- Published
- 1995
- Full Text
- View/download PDF
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