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220 results on '"O’Brien, Richard"'

2. Effect of viewing angles on measurement errors when using an implant cantilever beam torque-limiting device.

Author

Wadhwani, Chandur P.K., O'Brien, Richard, Rosen, Paul S., and Chung, Kwok-Hung

Abstract

Implant cantilever beam torque-limiting devices are affected by parallax, which may result in measurement read error. The overread or underread of the true target torque value could lead to premature failure of the screw joint of a dental implant. The purpose of this in vitro study was to determine the effect of the operator's viewing angle relative to the cantilever beam and measurement reading scale when the torque-limiting device is actioned toward or away from the operator. A beam torque wrench (Nobel Biocare USA) was used with the cantilever beam position fixed by using a wedge to read 32 Ncm on the marker arm. It was suspended in a vertical position relative to a digital single-lens reflex camera set at a fixed distance of 48 cm from the marker reading. The camera was rotated in 10-degree increments clockwise and counterclockwise relative to the cantilever beam reading, starting perpendicular to the marker. Photographs were recorded at each angle. Percentage measurement read error was calculated from dimensions of the cantilever beam torque device, including the beam diameter, distance from the marker arm, and the incremental marks on the measurement scale. Data were analyzed descriptively to determine the differences after comparison with the International Organization for Standardization (ISO) 6789-1:2017 recommendations. Photographs compared beam position relative to the 32-Ncm marker. The beam diameter was recorded as 1.5 mm, corresponding to approximately 5 Ncm. The distance between the marker arm and center of the beam was 0.08 mm. Percentage errors were greatest at lower torque values and increased relative to the viewing angle. Photographs showed that instrument overread was most likely to occur as the beam was moved away from the operator, which would result in potential undertightening unless compensated for. Underread was noted when the beam was pulled toward the operator. To prevent measurement read error when using an implant cantilever beam torque-limiting device, the operator should be positioned as close to a perpendicular viewing angle to the cantilever beam as possible. Viewing from an angle greater than 10 degrees from the perpendicular should be avoided for torque values less than 15 Ncm. For screws tightened between 25 Ncm and 35 Ncm, the viewing angle should be less than 30 degrees so that the applied torque is within the maximum deviation of the target torque value set by the ISO 6789-1:2017 recommendations. [ABSTRACT FROM AUTHOR]

Published
2023
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3. Neuropsychiatric co‐morbidities and psychotropic medication use in Medicare beneficiaries with dementia.

Author

Johnson, Kim G, Ford, Cassie, Clark, Amy G, Greiner, Melissa, Lusk, Jay, Perry, Cody, O'Brien, Richard, and O'Brien, Emily C

Abstract

Background: Neuropsychiatric symptoms affect approximately 97% of patients with dementia. Prevalence of symptoms may be different dependent upon age, sex or race. Past studies report high rates of potentially inappropriate prescribing in the dementia population. We investigate differences in neuropsychiatric diagnoses and psychotropic medication prescribing in a local US cohort. Method: We utilize Medicare claims and Medicare Part D prescription fill records in a cohort of 100% Medicare North and South Carolina fee‐for‐service beneficiaries ages 50 and above for the year 2017 with a dementia diagnosis. We identify dementia based on an ICD‐10‐CM diagnosis of dementia from an inpatient, outpatient, carrier, skilled nursing facility or home health claim, or a prescription claim for drug treatment between 1/1/2017 and 12/31/2017. We quantified neuropsychiatric diagnosis of anxiety, depression and psychosis using validated coding algorithms, searching inpatient, outpatient and physician 2017 claims. Demographic characteristics, including age, sex and race, as well as dual Medicare/Medicaid status were collected from the MSBF file for each individual. We search generic medication names in Medicare Part D claims for anti‐anxiety, antidepressant and antipsychotic medications to determine prescriptions filled during 2017. Result: Providers diagnosed anxiety and depression at higher rates in White patients; and psychosis at higher rates in Black patients. (P<0.001) Providers diagnosed female patients with depression, anxiety and psychosis at higher rates than males. (P<0.001) A provider diagnosis of anxiety, depression or psychosis is most prevalent in the age group 50‐59 and decreases with age to age 90+. Females with anxiety, depression and psychosis filled more anti‐anxiety and antidepressant medications than males. (P<0.001) Black and Other race patients filled more antipsychotic medications for anxiety and depression than White patients. (P<0.001) Conclusion: Of concern is the high fill rate of anti‐anxiety (benzodiazepine) medications, especially in females. In patients with a neuropsychiatric diagnosis, consistently over half filled an antidepressant medication and over a quarter filled prescriptions for antipsychotics. These medications may have risks > benefits in this population and lack efficacy. As alternatives, non‐pharmacologic treatment with patient/caregiver education about expectations and psychosocial interventions show promise. Innovative community outreach and care delivery models incorporating these methods may help decrease levels of medication use. [ABSTRACT FROM AUTHOR]

Published
2023
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4. Racial/ethnic disparities in dementia incidence, outcomes, and health‐care utilization.

Author

Lusk, Jay B., Ford, Cassie, Clark, Amy G., Greiner, Melissa A., Johnson, Kim, Goetz, Margarethe, Kaufman, Brystana G., Mantri, Sneha, Xian, Ying, O'Brien, Richard, and O'Brien, Emily C.

Abstract

Introduction: Racial/ethnic disparities exist in many aspects of health care, but data on racial/ethnic disparities for neurodegenerative diseases (NDDs), such as dementia and Parkinson's disease (PD), are limited. Methods: We used North and South Carolina Medicare claims from 2013 to 2017 to evaluate disparities in incidence of NDDs and in health‐care utilization and outcomes for patients with NDDs. Results: Disparities in incidence of NDD between Black and White beneficiaries narrowed by 0.37 per 100 person‐years from 2014 to 2017. After thorough covariate adjustment, Black beneficiaries had a 4% higher risk of all‐cause hospitalization, spent 8% more days in skilled nursing facilities and 14% fewer days in hospice facilities, were 38% less likely to receive physical/occupational therapy services, were 8% less likely to receive dementia medications, and were 19% less likely to receive PD medications than White beneficiaries. Discussion: Effective system‐level approaches to promote health equity in NDD diagnosis, treatment, and outcomes are clearly needed. Highlights: Racial disparities in neurodegenerative disease incidence narrowed between 2014 and 2017.Black patients were less likely than White patients to receive hospice services.Black patients were less likely than White patients to receive physical therapy.Black patients were less likely than White patients to receive Alzheimer's disease or Parkinson's disease medications.There is a shortage of neurologists in counties with high dementia incidence. [ABSTRACT FROM AUTHOR]

Published
2023
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5. Physical and Electrochemical Analysis of N-Alkylpyrrolidinium-Substituted Boronium Ionic Liquids

Author

Stachurski, Christopher D., Davis, James H., Cosby, Tyler, Crowley, Margaret E., Larm, Nathaniel E., Ballentine, Mollie G., O’Brien, Richard A., Zeller, Matthias, Salter, E. Alan, Wierzbicki, Andrzej, Trulove, Paul C., and Durkin, David P.

Abstract

In this work, a series of novel boronium-bis(trifluoromethylsulfonyl)imide [TFSI–] ionic liquids (IL) are introduced and investigated. The boronium cations were designed with specific structural motifs that delivered improved electrochemical and physical properties, as evaluated through cyclic voltammetry, broadband dielectric spectroscopy, densitometry, thermogravimetric analysis, and differential scanning calorimetry. Boronium cations, which were appended with N-alkylpyrrolidinium substituents, exhibited superior physicochemical properties, including high conductivity, low viscosity, and electrochemical windows surpassing 6 V. Remarkably, the boronium ionic liquid functionalized with both an ethyl-substituted pyrrolidinium and trimethylamine, [(1-e-pyrr)N111BH2][TFSI], exhibited a 6.3 V window, surpassing previously published boronium-, pyrrolidinium-, and imidazolium-based IL electrolytes. Favorable physical properties and straightforward tunability make boronium ionic liquids promising candidates to replace conventional organic electrolytes for electrochemical applications requiring high voltages.

Published
2023
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7. Cyclopropane as an Unsaturation “Effect Isostere”: Lowering the Melting Points in Lipid-like Ionic Liquids

Author

O’Brien, Richard A., Hillesheim, Patrick C., Soltani, Mohammad, Badilla-Nunez, Kelly J., Siu, Ben, Musozoda, Muhammadiqboli, West, Kevin N., Davis, James H., and Mirjafari, Arsalan

Abstract

The replacement of unsaturation with a cyclopropane motif as a (bio)isostere is a widespread strategy in bacteria to tune the fluidity of lipid bilayers and protect membranes when exposed to adverse environmental conditions, e.g., high temperature, low pH, etc. Inspired by this phenomenon, we herein address the relative effect of the cyclopropanation, both cisand transconfigurations, on melting points, packing efficiency, and order of a series of lipid-like ionic liquids via a combination of thermophysical analysis, X-ray crystallography, and computational modeling. The data indicate there is considerable structural latitude possible when designing highly lipophilic ionic liquids that exhibit low melting points. While cyclopropanation of the lipid-like ionic liquids provides more resistance to aerobic degradation than their olefin analogs, the impact on the melting point decrease is not as pronounced. Our results demonstrate that incorporating one or more cyclopropyl moieties in long aliphatic chains of imidazolium-based ionic liquids is highly effective in lowering the melting points of such materials relative to their counterparts bearing linear, saturated, or thioether side chains. It is shown that the cyclopropane moiety effectively disrupts packing, favoring formation of gaucheconformer in the side chains, resulting in enhancement of fluidity. This was irrespective of the configuration of the methylene bridge, although marked differences in the effect of cis- and trans-monocyclopropanated ILs on the melting points were observed.

Published
2023
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8. Validating implant torque limiting devices with a custom tool: A dental technique.

Author

O'Brien, Richard, Wadhwani, Chandur P.K., Rosen, Paul S., and Chung, Kwok-Hung

Abstract

The dental torque limiting device is a tool used to deliver a measured torque to implants and to their associated components. The torque delivery must be accurate and precise, especially when considering screw joints. Similar torque wrenches are used in various industries, and recommendations on calibration are provided by the International Organization for Standardization 6789-2:2017. It states that hand torque tools should be calibrated annually or more frequently if subjected to extreme temperature conditions such as steam sterilization. The International Organization for Standardization standard recommends that calibration may be performed by direct comparison of 2 torque devices provided that 1 is known to be within calibration. This technique article describes the procedures for fabricating a tool that couples 2 dental torque limiting devices. It may be used for calibrating and validating both electrical and mechanical torque limiting devices. [ABSTRACT FROM AUTHOR]

Published
2021
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9. Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Author

Halliday, Alison, Bulbulia, Richard, Bonati, Leo H, Chester, Johanna, Cradduck-Bamford, Andrea, Peto, Richard, Pan, Hongchao, Halliday, Alison, Bulbulia, Richard, Bonati, Leo H, Peto, Richard, Pan, Hongchao, Potter, John, Henning Eckstein, Hans, Farrell, Barbara, Flather, Marcus, Mansfield, Averil, Mihaylova, Boby, Rahimi, Kazim, Simpson, David, Thomas, Dafydd, Sandercock, Peter, Gray, Richard, Molyneux, Andrew, Shearman, Cliff P, Rothwell, Peter, Belli, Anna, Herrington, Will, Judge, Parminder, Leopold, Peter, Mafham, Marion, Gough, Michael, Cao, Piergiorgio, MacDonald, Sumaira, Bari, Vasha, Berry, Clive, Bradshaw, S, Brudlo, Wojciech, Clarke, Alison, Chester, Johanna, Cox, Robin, Cradduck-Bamford, Andrea, Fathers, Susan, Gaba, Kamran, Gray, Mo, Hayter, Elizabeth, Holliday, Constance, Kurien, Rijo, Lay, Michael, le Conte, Steffi, McManus, Jessica, Madgwick, Zahra, Morris, Dylan, Munday, Andrew, Pickworth, Sandra, Ostasz, Wiktor, Poorthuis, Michiel, Richards, Sue, Teixeira, Louisa, Tochlin, Sergey, Tully, Lynda, Wallis, Carol, Willet, Monique, Young, Alan, Casana, Renato, Malloggi, Chiara, Odero Jr, Andrea, Silani, Vincenzo, Parati, Gianfranco, Malchiodi, Giuseppe, Malferrari, Giovanni, Strozzi, Francesco, Tusini, Nicola, Vecchiati, Enrico, Coppi, Gioacchino, Lauricella, Antonio, Moratto, Roberto, Silingardi, Roberto, Veronesi, Jessica, Zini, Andrea, Ferrero, Emanuele, Ferri, Michelangelo, Gaggiano, Andrea, Labate, Carmelo, Nessi, Franco, Psacharopulo, Daniele, Viazzo, Andrea, Malacrida, Giovanni, Mazzaccaro, Daniela, Meola, Giovanni, Modafferi, Alfredo, Nano, Giovanni, Occhiuto, Maria Teresa, Righini, Paolo, Stegher, Silvia, Chiarandini, Stefano, Griselli, Filippo, Lepidi, Sandro, Pozzi Mucelli, Fabio, Naccarato, Marcello, D'Oria, Mario, Ziani, Barbara, Stella, Andrea, Dieng, Mortalla, Faggioli, Gianluca, Gargiulo, Mauro, Palermo, Sergio, Pini, Rodolfo, Puddu, Giovanni Maria, Vacirca, Andrea, Angiletta, Domenico, Desantis, Claudio, Marinazzo, Davide, Mastrangelo, Giovanni, Regina, Guido, Pulli, Raffaele, Bianchi, Paolo, Cireni, Lea, Coppi, Elisabetta, Pizzirusso, Rocco, Scalise, Filippo, Sorropago, Giovanni, Tolva, Valerio, Caso, Valeria, Cieri, Enrico, DeRango, Paola, Farchioni, Luca, Isernia, Giacomo, Lenti, Massimo, Parlani, Gian Battista, Pupo, Guglielmo, Pula, Grazia, Simonte, Gioele, Verzini, Fabio, Carimati, Federico, Delodovici, Maria Luisa, Fontana, Federico, Piffaretti, Gabriele, Tozzi, Matteo, Civilini, Efrem, Poletto, Giorgio, Reimers, Bernhard, Praquin, Barbara, Ronchey, Sonia, Capoccia, Laura, Mansour, Wassim, Sbarigia, Enrico, Speziale, Francesco, Sirignano, Pasqualino, Toni, Danilo, Galeotti, Roberto, Gasbarro, Vincenzo, Mascoli, Francesco, Rocca, Tiberio, Tsolaki, Elpiniki, Bernardini, Giulia, DeMarco, Ester, Giaquinta, Alessia, Patti, Francesco, Veroux, Massimiliano, Veroux, Pierfrancesco, Virgilio, Carla, Mangialardi, Nicola, Orrico, Matteo, Di Lazzaro, Vincenzo, Montelione, Nunzio, Spinelli, Francesco, Stilo, Francesco, Cernetti, Carlo, Irsara, Sandro, Maccarrone, Giuseppe, Tonello, Diego, Visonà, Adriana, Zalunardo, Beniamino, Chisci, Emiliano, Michelagnoli, Stefano, Troisi, Nicola, Masato, Maela, Dei Negri, Massimo, Pacchioni, Andrea, Saccà, Salvatore, Amatucci, Giovanni, Cannizzaro, Alfredo, Accrocca, Federico, Ambrogi, Cesare, Barbazza, Renzo, Marcucci, Giustino, Siani, Andrea, Bajardi, Guido, Savettieri, Giovanni, Argentieri, Angelo, Corbetta, Riccardo, Odero, Attilio, Quaretti, Pietro, Thyrion, Federico Z, Cappelli, Alessandro, Benevento, Domenico, De Donato, Gianmarco, Mele, Maria Agnese, Palasciano, Giancarlo, Pieragalli, Daniela, Rossi, Alessandro, Setacci, Carlo, Setacci, Francesco, Palombo, Domenico, Perfumo, Maria Cecilia, Martelli, Edoardo, Paolucci, Aldo, Trimarchi, Santi, Grassi, Viviana, Grimaldi, Luigi, La Rosa, Giuliana, Mirabella, Domenico, Scialabba, Matteo, Sichel, Leonildo, D'Angelo, Costantino L, Fadda, Gian Franco, Kasemi, Holta, Marino, Mario, Burzotta, Francesco, Codispoti, Francesco Alberto, Ferrante, Angela, Tinelli, Giovanni, Tshomba, Yamume, Vincenzoni, Claudio, Amis, Deborah, Anderson, Dawn, Catterson, Martin, Clarke, Mike, Davis, Michelle, Dixit, Anand, Dyker, Alexander, Ford, Gary, Jackson, Ralph, Kappadath, Sreevalsan, Lambert, David, Lees, Tim, Louw, Stephen, McCaslin, James, Parr, Noala, Robson, Rebecca, Stansby, Gerard, Wales, Lucy, Wealleans, Vera, Wilson, Lesley, Wyatt, Michael, Baht, Hardeep, Balogun, Ibrahim, Burger, Ilse, Cosier, Tracy, Cowie, Linda, Gunathilagan, Gunaratnam, Hargroves, David, Insall, Robert, Jones, Sally, Rudenko, Hannah, Schumacher, Natasha, Senaratne, Jawaharlal, Thomas, George, Thomson, Audrey, Webb, Tom, Brown, Ellen, Esisi, Bernard, Mehrzad, Ali, MacSweeney, Shane, McConachie, Norman, Southam, Alison, Sunman, Wayne, Abdul-Hamiq, Ahmed, Bryce, Jenny, Chetter, Ian, Ettles, Duncan, Lakshminarayan, Raghuram, Mitchelson, Kim, Rhymes, Christopher, Robinson, Graham, Scott, Paul, Vickers, Alison, Ashleigh, Ray, Butterfield, Stephen, Gamble, Ed, Ghosh, Jonathan, McCollum, Charles N, Welch, Mark, Welsh, Sarah, Wolowczyk, Leszek, Donnelly, Mary, D'Souza, Stephen, Egun, Anselm A, Gregary, Bindu, Joseph, Thomas, Kelly, Christine, Punekar, Shuja, Rahi, M Asad, Raj, Sonia, Seriki, Dare, Thomson, George, Brown, James, Durairajan, Ragunath, Grunwald, Iris, Guyler, Paul, Harman, Paula, Jakeways, Matthew, Khuoge, Christopher, Kundu, Ashish, Loganathan, Thayalini, Menon, Nisha, Prabakaran, Raji O, Sinha, Devesh, Thompson, Vicky, Tysoe, Sharon, Briley, Dennis, Darby, Chris, Hands, Linda, Howard, Dominic, Kuker, Wilhelm, Schulz, Ursula, Teal, Rachel, Barer, David, Brown, Andrew, Crawford, Susan, Dunlop, Paul, Krishnamurthy, Ramesh, Majmudar, Nikhil, Mitchell, Duncan, Myint, Min P, O'Brien, Richard, O'Connell, Janice, Sattar, Naweed, Vetrivel, Shanmugam, Beard, Jonathan, Cleveland, Trevor, Gaines, Peter, Humphreys, John, Jenkins, Alison, King, Craig, Kusuma, Daniel, Lindert, Ralph, Lonsdale, Robbie, Nair, Raj, Nawaz, Shah, Okhuoya, Faith, Turner, Douglas, Venables, Graham, Dorman, Paul, Hughes, Andrea, Jones, Deborah, Mendelow, David, Rodgers, Helen, Raudoniitis, Aidas, Enevoldson, Peter, Nahser, Hans, O'Brien, Imelda, Torella, Francesco, Watling, Dave, White, Richard, Brown, Pauline, Dutta, Dipankar, Emerson, Lorraine, Hilltout, Paula, Kulkarni, Sachin, Morrison, Jackie, Poskitt, Keith, Slim, Fiona, Smith, Sarah, Tyler, Amanda, Waldron, Joanne, Whyman, Mark, Bajoriene, Milda, Baker, Lucy, Colston, Amanda, Eliot-Jones, Bekky, Gramizadeh, Gita, Lewis-Clarke, Catherine, McCafferty, Laura, Oliver, Deborah, Palmer, Debbie, Patil, Abhijeet, Pegler, Suzannah, Ramadurai, Gopi, Roberts, Aisling, Sargent, Tracey, Siddegowda, Shivaprasad, Singh-Ranger, Ravi, Williams, Akintunde, Williams, Lucy, Windebank, Steve, Zuromskis, Tadas, Alwis, Lanka, Angus, Jane, Asokanathan, Asaipillai, Fornolles, Caroline, Hardy, Diana, Hunte, Sophy, Justin, Frances, Phiri, Duke, Mitabouana-Kibou, Marie, Sekaran, Lakshmanan, Sethuraman, Sakthivel, Tate, Margaret L, Akyea-Mensah, Joyce, Ball, Stephen, Chrisopoulou, Angela, Keene, Elizabeth, Phair, Alison, Rogers, Steven, Smyth, John V, Bicknell, Colin, Chataway, Jeremy, Cheshire, Nicholas, Clifton, Andrew, Eley, Caroline, Gibbs, Richard, Hamady, Mohammad, Hazel, Beth, James, Alex, Jenkins, Michael, Khanom, Nyma, Lacey, Austin, Mireskandari, Maz, O'Reilly, Joanna, Pereira, Antony, Sachs, Tina, Wolfe, John, Brown, Ellen, Davey, Philip, Rogers, Gill, Smith, Gemma, Tervit, Gareth, Nichol, Ian, Parry, Andrew, Young, Gavin, Ashley, Simon, Barwell, James, Dix, Francis, Nor, Azlisham M, Parry, Chris, Birt, Angela, Davies, Paul, George, Jim, Graham, Anne, Jonker, Leon, Joseph, Thomas, Kelsall, Nicci, Potts, Caroline, Wilson, Toni, Clifton, Andrew, Crinnion, Jamie, Cuenoud, Larissa, Aleksic, Nikola, Babic, Srdan, Ilijevski, Nenad, Radak, Đorde, Sagic, Dragan, Tanaskovic, Slobodan, Colic, Momcilo, Cvetic, Vladimir, Davidovic, Lazar, Jovanovic, Dejana R, Koncar, Igor, Mutavdžic, Perica, Sladojevic, Miloš, Tomic, Ivan, Debus, Eike S, Grzyska, Ulrich, Otto, Dagmar, Thomalla, Götz, Barlinn, Jessica, Gerber, Johannes, Haase, Kathrin, Hartmann, Christian, Ludwig, Stefan, Pütz, Volker, Reeps, Christian, Schmidt, Christine, Weiss, Norbert, Werth, Sebastian, Winzer, Simon, Gemper, Janine, Günther, Albrecht, Heiling, Bianka, Jochmann, Elisabeth, Karvouniari, Panagiota, Klingner, Carsten, Mayer, Thomas, Schubert, Julia, Schulze-Hartung, Friederike, Zanow, Jürgen, Bausback, Yvonne, Borger, Franka, Botsios, Spiridon, Branzan, Daniela, Bräunlich, Sven, Hölzer, Henryk, Lenzer, Janin, Piorkowski, Christopher, Richter, Nadine, Schuster, Johannes, Scheinert, Dierk, Schmidt, Andrej, Staab, Holger, Ulrich, Matthias, Werner, Martin, Berger, Hermann, Biró, Gábor, Eckstein, Hans-Henning, Kallmayer, Michael, Kreiser, Kornelia, Zimmermann, Alexander, Berekoven, Bärbel, Frerker, Klaus, Gordon, Vera, Torsello, Giovanni, Arnold, Sebastian, Dienel, Cora, Storck, Martin, Biermaier, Bernhard, Gissler, Hans Martin, Klötzsch, Christof, Pfeiffer, Tomas, Schneider, Ralph, Söhl, Leander, Wennrich, Michael, Alonso, Angelika, Keese, Michael, Groden, Christoph, Cöster, Andreas, Engelhardt, Andreas, Ratusinski, Christoph-Maria, Berg, Bengt, Delle, Martin, Formgren, Johan, Gillgren, Peter, Jarl, Lotta, Kall, Torbjörn B, Konrad, Peter, Nyman, Niklas, Skiöldebrand, Claes, Steuer, Johnny, Takolander, Rabbe, Malmstedt, Jonas, Acosta, Stefan, Björses, Katarina, Brandt, Kerstin, Dias, Nuno, Gottsäter, Anders, Holst, Jan, Kristmundsson, Thorarinn, Kühme, Tobias, Kölbel, Tilo, Lindblad, Bengt, Lindh, Mats, Malina, Martin, Ohrlander, Tomas, Resch, Tim, Rönnle, Viola, Sonesson, Björn, Warvsten, Margareta, Zdanowski, Zbigniew, Campbell, Erik, Kjellin, Per, Lindgren, Hans, Nyberg, Johan, Petersen, Björn, Plate, Gunnar, Pärsson, Håkan, Qvarfordt, Peter, Ignatenko, Pavel, Karpenko, Andrey, Starodubtsev, Vladimir, Chernyavsky, Mikhail A, Golovkova, Maria S, Komakha, Boris B, Zherdev, Nikolay N, Belyasnik, Andrey, Chechulov, Pavel, Kandyba, Dmitry, Stepanishchev, Igor, Csobay-Novák, Csaba, Dósa, Edit, Entz, László, Nemes, Balázs, Szeberin, Zoltán, Barzó, Pál, Bodosi, Mihaly, Fákó, Eniko, Fülöp, Béla, Németh, Tamás, Pazdernyik, Szilárd, Skoba, Krisztina, Vörös, Erika, Chatzinikou, Eleni, Giannoukas, Athanasios, Karathanos, Christos, Koutsias, Stylianos, Kouvelos, Georgios, Matsagkas, Miltiadis, Ralli, Styliani, Rountas, Christos, Rousas, Nikolaos, Spanos, Konstantinos, Brountzos, Elias, Kakisis, John D, Lazaris, Andreas, Moulakakis, Konstantinos G, Stefanis, Leonidas, Tsivgoulis, Georgios, Vasdekis, Spyros, Antonopoulos, Constantine N, Bellenis, Ion, Maras, Dimitrios, Polydorou, Antonios, Polydorou, Victoria, Tavernarakis, Antonios, Ioannou, Nikolaos, Terzoudi, Maria, Lazarides, Miltos, Mantatzis, Michalis, Vadikolias, Kostas, Dzieciuchowicz, Lukasz, Gabriel, Marcin, Krasinski, Zbigniew, Oszkinis, Grzegorz, Pukacki, Fryderyk, Slowinski, Maciej, Stanišic, Michal-Goran, Staniszewski, Ryszard, Tomczak, Jolanta, Zielinski, Maciej, Myrcha, Piotr, Rózanski, Dorota, Drelichowski, Stanislaw, Iwanowski, Wojciech, Koncewicz, Katarzyna, Bialek, Pawel, Biejat, Zbigniew, Czepel, Wojciech, Czlonkowska, Anna, Dowzenko, Anatol, Jedrzejewska, Julia, Kobayashi, Adam, Leszczynski, Jerzy, Malek, Andrzej, Polanski, Jerzy, Proczka, Robert, Skorski, Maciej, Szostek, Mieczyslaw, Andziak, Piotr, Dratwicki, Maciej, Gil, Robert, Nowicki, Miroslaw, Pniewski, Jaroslaw, Rzezak, Jaroslaw, Seweryniak, Piotr, Dabek, Pawel, Juszynski, Michal, Madycki, Grzegorz, Pacewski, Bartosz, Raciborski, Witold, Slowinski, Piotr, Staszkiewicz, Walerian, Bombic, Martin, Chlouba, Vladimír, Fiedler, Jirí, Hes, Karel, Koštál, Petr, Sova, Jindrich, Kríž, Zdenek, Prívara, Mojmír, Reif, Michal, Staffa, Robert, Vlachovský, Robert, Vojtíšek, Bohuslav, Hrbác, Tomáš, Kuliha, Martin, Procházka, Václav, Roubec, Martin, Školoudík, David, Netuka, David, Šteklácová, Anna, Beneš III, Vladimír, Buchvald, Pavel, Endrych, Ladislav, Šercl, Miroslav, Campos Jr, Walter, Casella, Ivan B, de Luccia, Nelson, Estenssoro, André E V, Presti, Calógero, Puech-Leão, Pedro, Neves, Celso R B, da Silva, Erasmo S, Sitrângulo Jr, Cid J, Monteiro, José A T, Tinone, Gisela, Bellini Dalio, Marcelo, Joviliano, Edwaldo E, Pontes Neto, Octávio M, Serra Ribeiro, Mauricio, Cras, Patrick, Hendriks, Jeroen M H, Hoppenbrouwers, Mieke, Lauwers, Patrick, Loos, Caroline, Yperzeele, Laetitia, Geenens, Mia, Hemelsoet, Dimitri, van Herzeele, Isabelle, Vermassen, Frank, Astarci, Parla, Hammer, Frank, Lacroix, Valérie, Peeters, André, Verhelst, Robert, Cirelli, Silvana, Dormal, Pol, Grimonprez, Annelies, Lambrecht, Bart, Lerut, Philipe, Thues, Eddy, De Koster, Guy, Desiron, Quentin, Maertens de Noordhout, Alain, Malmendier, Danielle, Massoz, Mireille, Saad, Georges, Bosiers, Marc, Callaert, Joren, Deloose, Koen, Blanco Cañibano, Estrella, García Fresnillo, Beatriz, Guerra Requena, Mercedes, Morata Barrado, Pilar C, Muela Méndez, Miguel, Yusta Izquierdo, Antonio, Aparici Robles, Fernando, Blanes Orti, Paula, García Dominguez, Luis, Martínez López, Rafael, Miralles Hernández, Manuel, Tembl Ferrairo, José I, Chamorro, Ángel, Macho, Juan, Obach, Víctor, Riambau, Vincent, San Román, Luis, Ahlhelm, Frank J, Blackham, Kristine, Engelter, Stefan, Eugster, Thomas, Gensicke, Henrik, Gürke, Lorenz, Lyrer, Philippe, Mariani, Luigi, Maurer, Marina, Mujagic, Edin, Müller, Mandy, Psychogios, Marios, Stierli, Peter, Stippich, Christoph, Traenka, Christopher, Wolff, Thomas, Wagner, Benjamin, Wiegert, Martina M, Clarke, Sandra, Diepers, Michael, Gröchenig, Ernst, Gürke, Lorenz, Gruber, Philipp, Isaak, Andrej, Kahles, Timo, Marti, Regula, Nedeltchev, Krassen, Remonda, Luca, Stierli, Peter, Tissira, Nadir, Valença Falcão, Martina, de Borst, Gert J, Lo, Rob H, Moll, Frans L, Toorop, Raechel, van der Worp, Bart H, Vonken, Evert J, Kappelle, Jaap L, Jahrome, Ommid, Vos, Floris, Schuiling, Wouter, van Overhagen, Hendrik, Keunen, Rudolf W M, Knippenberg, Bob, Wever, Jan J, Lardenoije, Jan W, Reijnen, Michel, Smeets, Luuk, van Sterkenburg, Steven, Fraedrich, Gustav, Gizewski, Elke, Gruber, Ingrid, Knoflach, Michael, Kiechl, Stefan, Rantner, Barbara, Abdulamit, Timur, Bergeron, Patrice, Padovani, Raymond, Trastour, Jean-Christophe, Cardon, Jean-Marie, Le Gallou-Wittenberg, Anne, Allaire, Eric, Becquemin, Jean-Pierre, Cochennec-Paliwoda, Frédéric, Desgranges, Pascal, Hosseini, Hassan, Kobeiter, Hicham, Marzelle, Jean, Almekhlafi, Mohammed A, Bal, Simerpreet, Barber, Phillip A, Coutts, Shelagh B, Demchuk, Andrew M, Eesa, Muneer, Gillies, Michelle, Goyal, Mayank, Hill, Michael D, Hudon, Mark E, Jambula, Anitha, Kenney, Carol, Klein, Gary, McClelland, Marie, Mitha, Alim, Menon, Bijoy K, Morrish, William F, Peters, Steven, Ryckborst, Karla J, Samis, Greg, Save, Supriya, Smith, Eric E, Stys, Peter, Subramaniam, Suresh, Sutherland, Garnette R, Watson, Tim, Wong, John H, Zimmel, L, Flis, Vojko, Matela, Jože, Miksic, Kazimir, Milotic, Franko, Mrdja, Božidar, Stirn, Barbara, Tetickovic, Erih, Gasparini, Mladen, Grad, Anton, Kompara, Ingrid, Miloševic, Zoren, Palmiste, Veronika, Toomsoo, Toomas, Aidashova, Balzhan, Kospanov, Nursultan, Lyssenko, Roman, Mussagaliev, Daulet, Beyar, Rafi, Hoffman, Aaron, Karram, Tony, Kerner, Arthur, Nikolsky, Eugenia, Nitecki, Samy, Andonova, Silva, Bachvarov, Chavdar, Petrov, Vesko, Cvjetko, Ivan, Vidjak, Vinko, Halužan, Damir, Petrunic, Mladen, Liu, Bao, Liu, Chang-Wei, Bartko, Daniel, Beno, Peter, Rusnák, František, Zelenák, Kamil, Ezura, Masayuki, Inoue, Takashi, Kimura, Naoto, Kondo, Ryushi, Matsumoto, Yasushi, Shimizu, Hiroaki, Endo, Hidenori, Furui, Eisuke, Bakke, Søren, Krohg-Sørensen, Kristen, Nome, Terje, Skjelland, Mona, Tennøe, Bjørn, Albuquerque e Castro, João, Alves, Gonçalo, Bastos Gonçalves, Frederico, de Aragão Morais, José, Garcia, Ana C, Valentim, Hugo, Vasconcelos, Leonor, Belcastro, Fernando, Cura, Fernando, Zaefferer, Patricio, Abd-Allah, Foad, Eldessoki, Mohamed H, Heshmat Kassem, Hussein, Soliman Gharieb, Haytham, Colgan, Mary P, Haider, Syed N, Harbison, Joe, Madhavan, Prakash, Moore, Dermot, Shanik, Gregor, Kazan, Viviane, Nazzal, Munier, and Ramsey-Williams, Vicki

Abstract

Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence.

Published
2021
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10. A technique to validate the accuracy of a beam-type mechanical torque limiting device.

Author

Wadhwani, Chandur P.K., O'Brien, Richard T., Rosen, Paul S., and Chung, Kwok-Hung

Abstract

Tightening torques are often specified in implant dentistry, including for surgical procedures, testing implant stability, and attaching prosthetic components when screws are used. The mechanical torque limiting devices (MTLDs) commonly used are typically either a toggle-type or beam-type. The International Organization for Standardization (ISO) 6789 recommends MTLDs should be periodically tested to confirm the validity of their readings, and, where necessary, recalibrated if possible or replaced. The verification of the toggle-type MLTD has been previously published. This article describes a straightforward, in-office technique to verify a beam-type MTLD. [ABSTRACT FROM AUTHOR]

Published
2020
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12. Testing and calibrating the mechanical-type toggle torque wrenches used in implant dentistry: A dental technique.

Author

Wadhwani, Chandur P.K., O'Brien, Richard, Rosen, Paul S., and Chung, Kwok-Hung

Abstract

Abutment screw loosening is still the most common complication reported with implant-supported crowns. One factor that contributes to screw loosening is not achieving the proper torque during the tightening process. Torque application and measurement is usually achieved by using one of the available types of mechanical torque wrench. Of these, the toggle wrench has been shown to produce erroneous readings, and regular testing is recommended. If it is inaccurate, it must be recalibrated or replaced. Calibration typically requires specialized instruments unavailable to most clinicians, so the device must be sent away. This article describes a straightforward, in-office, and inexpensive alternative for testing and recalibrating a toggle torque wrench. [ABSTRACT FROM AUTHOR]

Published
2020
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13. Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Author

Al-Shahi Salman, Rustam, Dennis, MS, Sandercock, PAG, Sudlow, CLM, Wardlaw, JM, Whiteley, WN, Murray, GD, Stephen, J, Newby, DE, Sprigg, N, Werring, DJ, White, PM, Baigent, Colin, Lasserson, Daniel, Sullivan, Frank, Carrie, Johanna, Rojas, Javier, Amoils, Shannon, Bamford, John, Armitage, Jane, Rinkel, Gabriel, Lowe, Gordon, Emberson, Jonathan, Innes, Karen, Dinsmore, Lynn, Drever, Jonathan, Williams, Carol, Perry, David, McGill, Connor, Buchanan, David, Walker, Allan, Hutchison, Aidan, Matthews, Christopher, Fraser, Ruth, McGrath, Aileen, Deary, Ann, Anderson, Rosemary, Walker, Pauli, Hansen, Christian, Parker, Richard, Rodriguez, Aryelly, Macleod, MR, Gattringer, Thomas, Palmer, Jeb, Sakka, Eleni, Adil-Smith, Jennifer, Minks, David, Mitra, Dipayan, Bhatnagar, Priya, du Plessis, Johannes, Joshi, Yogish, Lerpiniere, Christine, O'Brien, Richard, Burgess, Seona, Mead, Gillian, Paulton, Ruth, Doubal, Fergus, McCormick, Katrina, Hunter, Neil, Taylor, Pat, Parakramawansha, Ruwan, Perry, Jack, Blair, Gordon, MacRaild, Allan, Parry-Jones, Adrian, Johnes, Mary, Lee, Stephanie, Shaw, Kelly Marie, Burger, Ilse, Punter, Martin, Ingham, Andrea, Perez, Jane, Naing, Zin, Morell, Jordi, Marsden, Tracy, Hall, Andrea, Marshall, Sally, Harrison, Louise, Jarapa, Rowilson, Wood, Edith, O'Loughlin, Victoria, Cohen, David, Davies, Silvie, Njoku, Kelechi, Mpelembue, Mushiya, Burgess, Laura, Licenik, Radim, Ngwako, Mmua, Nisar, Nabeela, Niranchanan, Rangah, Roganova, Tatjana, Bathula, Rajaram, Devine, Joseph, David, Anette, Oshodi, Anne, Guo, Fenglin, Owoyele, Emmanuelle, Sukdeo, Varthi, Ballantine, Robert, Abbdul-saheb, Mudhar, Chamberlain, Angela, Chandrakumar, Aberami, Poku, Philip, Harkness, Kirsty, Blank, Catrin, Richards, Emma, Ali, Ali, Kibutu, Faith, Balitska, Olesia, Birchall, Kathryn, Bayliss, Pauline, Doyle, Clare, Stocks, Kathy, Majis, Arshad, Howe, Jo, Kamara, Christine, Barron, Luke, Maatouk, Ahmad, Lindert, Ralf, Dakin, Katy, Redgrave, Jessica, Bhaskaran, Biju, Salih, Isam, Kelly, Debs, Szabo, Susan, Tomlin, Dawn, Bearne, Helen, Buxton, Jean, Fitzell, Pauline, Ayres, Georgina, Saulat, Afaq, Horan, Kathleen, Garfield-Smith, Joanne, Bhakri, Harbens, Guyler, Paul, Sinha, Devesh, Loganathan, Thayalini, Siddiqui, Amber, Siddiqui, Anwer, Coward, Lucy, Kunhunny, Swapna, Tysoe, Sharon, Orath Prabakaran, Rajalakshmi, Kelavkar, Shyam, Rashmi, Sindhu, Ngo, David, Ng, Kheng Xiong, Menon, Nisha, Shah, Sweni, Barber, Mark, Esson, Derek, Brodie, Fiona, Anjum, Talat, Wani, Mushtaq, Krishnan, Manju, Quinn, Leanne, Spencer, Jayne, Jones, Terry, Thompson-Jones, Helen, Dacey, Lynne, Chenna, Srikanth, Storton, Sharon, Thomas, Sarah, Beaty, Teresa, Treadwell, Shelley, Davies, Caroline, Tucker, Susan, Connor, Lynda, Slade, Peter, Gainard, Glyn, Muddegowda, Girish, Sanyal, Ranjan, Remegoso, Alda, Abano, Nenette, Causley, Chelsea, Carpio, Racquel, Stevens, Stephanie, Butler, Adrian, Varquez, Resti, Denic, Hayley, Alipio, Francis, Moores, Andrew, Barry, Adrian, Maguire, Holly, Grocott, Jeanette, Finney, Kay, Lyjko, Sue, Roffe, Christine, Hiden, Joanne, Ferdinand, Phillip, Cvoro, Vera, Ullah, Khalil, Chapman, Nicola, Couser, Mandy, Pound, Susan, McCormick, Katrina, Mcauley, Sean, Raghunathan, Senthil, Shelton, Faye, Hedstrom, Amanda, Godfrey, Margi, Havard, Diane, Buck, Amanda, Krishnan, Kailash, Gilzeane, Nicola, Roffe, Jack, Clarke, Judith, Whittamore, Katherine, Sheikh, Saima, Keshvara, Rekha, Jordan, Carla, Jackson, Benjamin, Wilkes, Gwendoline, Appleton, Jason, Law, Zhe, Matias, Oliver, Vasileiadis, Evangelos, Mason, Cathy, Parry, Anthea, Landers, Geraldine, Holden, Melinda, Aweid, Basaam, Rashed, Khalid, Balian, Linda, Vickers, Carinna, Keeling, Elizabeth, Board, Sarah, Allison, Joanna, Buckley, Clare, Williams-Yesson, Barbara, Board, Joanne, Pitt-Kerby, Tressy, Tanate, Alfonso, Wood, Diane, Kini, Manohar, Chadha, Dinesh, Walstow, Deborah, Fong, Rosanna, Luder, Robert, Adesina, Tolu, Gallagher, Jill, Bridger, Hayley, Murali, Elodie, Bhargava, Maneesh, van Someren, Chloe, Harrington, Frances, Mate, Abhijit, James, Ali, Courtauld, Gillian, Schofield, Christine, Adie, Katja, Lucas, Linda, Bond, Kirsty, Maund, Bev, Ellis, Sam, Mudd, Paul, James, Martin, Keenan, Samantha, Bowring, Angela, Cageao, Julie, Kingwell, Hayley, Roughan, Caroline, Hemsley, Anthony, Sword, Jane, Strain, David, Miller, Keniesha, Goff, Anita, Gupwell, Karin, Thorpe, Kevin, Emsley, Hedley, Punekar, Shuja, McLoughlin, Alison, Sultan, Sulaiman, Gregory, Bindu, Raj, Sonia, Doyle, Donna, Muir, Keith, Smith, Wilma, Welch, Angela, Moreton, Fiona, Cheripelli, Bharath Kumar, El Tawil, Salwa, Kalladka, Dheeraj, Huang, Xuya, Day, Nicola, Ramachandran, Sankaranarayanan, Crosbie, Caroline, Elliot, Jennifer, Rudd, Tony, Marks, Katherine, Bhalla, Ajay, Birns, Jonathan, Kullane, Sagal, Weir, Nic, Allen, Christopher, Pressly, Vanessa, Crawford, Pam, Battersby-Wood, Emma, Blades, Alex, Egerton, Shuna, Walters, Ashleigh, Evans, Sue, Marigold, James Richard, Smith, Fiona, Howard, Gabriella, Gartrell, Imogen, Smith, Simon, Creeden, Robyn, Cox, Chloe, Boxall, Cherish, Hewitt, Jonathan, Nott, Claire, Sarah, Procter, Whiteman, Jessica, Buckle, Steve, Wallace, Rebecca, Mardania, Rina, Gray, Jane, Triscott, Claire, Nair, Anand, Greig, Jill, Rana, Pratap, Robinson, Matthew, Alam, Mohammad Irfan, Wilson, Duncan, Watchurst, Caroline, Brezitski, Maria, Crook, Luci, Jones, Ifan, Banaras, Azra, Patel, Krishna, Erande, Renuka, Hogan, Caroline, Hostettler, Isabel, Ashton, Amy, Feerick, Shez, Francia, Nina, Oji, Nnebuife, Elliott, Emma, Al-Mayhani, Talal, Lerpiniere, Christine, Fraser, Ruth, Dutta, Dipankar, Brown, Pauline, Ward, Deborah, Davis, Fiona, Turfrey, Jennifer, Hughes, Chloe, Collins, Kayleigh, Bakawala, Rehana, O'Connell, Susan, Glass, Jon, Broughton, David, Tryambake, Dinesh, Dixon, Lynn, Chapman, Kath, Young, Andrew, Bergin, Adrian, Sigsworth, Andrew, Manoj, Aravind, Fletcher, Glyn, Lopez, Paula, Cox, Penelope, Wilkinson, Mark, Fitzsimmons, Paul, Sharma, Nikhil, Choulerton, James, Button, Denise, Dow, Lindsey, Gbadamoshi, Lukuman, Avis, Joanne, Madigan, Barbara, McCann, Stephanie, Shaw, Louise, Howcroft, Deborah, Lucas, Suzanne, Stone, Andrew, Cluckie, Gillian, Lovelock, Caroline, Clarke, Brian, Chopra, Neha, Clarke, Natasha, Patel, Bhavini, Kennedy, Kate, Williams, Rebecca, Blight, Adrian, O'Reilly, Joanna, Orefo, Chukwuka, Dayal, Nilofer, Ghatala, Rita, Adedoyin, Temi, Watson, Fran, Trippier, Sarah, Choy, Lillian, Moynihan, Barry, Khan, Usman, Jones, Val, Jeyaraj, Naomi, Kerin, Lourda, Thavanesan, Kamy, Tiwari, Divya, Cox, Chantel, Ljubez, Anja, Tucker, Laura, Iqbal, Arshi, Bagnall, Caroline, Keltos, Marketa, Roberts, Josh, Jupp, Becky, Ovington, Catherine, Rogers, Emily, David, Owen, Bell, Jo, Longland, Barbara, Hann, Gail, Cooper, Martin, Nasar, Mohammad, Rajapakse, Anoja, Wynter, Inez, Anwar, Ijaz, Skinner, Helen, Nozedar, Tarn, McArdle, Damian, Kumar, Balakrishna, Crawford, Susan, Annamalai, Arunkumar, Ramshaw, Alex, Holmes, Clare, Caine, Sarah, Osborn, Mairead, Dodd, Emily, Murphy, Peter, Devitt, Nicola, Baker, Pauline, Steele, Amy, Guthrie, Lucy Belle, Clarke, Samantha, Hassan, Ahamad, Waugh, Dean, Veraque, Emelda, Makawa, Linetty, Kambafwile, Mary, Randall, Marc, Papavasileiou, Vasileios, Cullen, Claire, Peters, Jenny, Thant, Hlaing, Ingram, Tanya, Zoe, Mellor, Durairaj, Ramesh, Harrison, Melanie, Stevenson, Sarah, Shackcloth, Daniela, Ewing, Jordan, Sutton, Victoria, McCarron, Mark, McKee, Jacqueline, Doherty, Mandy, McVerry, Ferghal, Blair, Caroline, MacLeod, Mary, Irvine, Janice, Gow, Heather, Furnace, Jacqueline, Joyson, Anu, Jagpal, Baljit, Ross, Sarah, Klaasen, Katrina, Nelson, Sandra, Clarke, Rebecca, Crouch, Nichola, MacLennan, Beverly, Taylor, Vicky, Epstein, Daniel, Jones, Ifan, Shukla, Avani, Krishnamurthy, Vinodh, Nicholas, Paul, Qureshi, Sammie, Webber, Adam, Penge, Justin, Ramadan, Hawraman, Maguire, Stuart, Patterson, Chris, Bellfield, Ruth, Hairsine, Brigid, Stewart, Kelvin, Hooley, Michaela, Quinn, Outi, Richard, Bella, Moseley, Sally, Nott, Claire, Buckle, Steve, Sarah, Procter, Whiteman, Jessica, Edwards, Mandy, Lawson, Heidi, Wallace, Rebecca, Triscott, Claire, Tayler, Michelle, Pai, Yogish, Dhakal, Mahesh, Esisi, Bernard, Dima, Sofia, Smith, Gemma Marie, Garside, Mark, Naeem, Muhammad, Baliga, Vidya, Rogers, Gill, Brown, Ellen, Bruce, David, Hayman, Rachel, Clayton, Susan, Gamble, Ed, Grue, Rebecca, Charles, Bethan, Hague, Adam, Blane, Sujata, Lambert, Caroline, Chaudhry, Afnan, Harrison, Thomas, Saastamoinen, Kari, Hove, Dionne, Howaniec, Laura, Grimwood, Gemma, Redjep, Ozlem, Humphries, Fiona, Argandona, Lucia, Cuenoud, Larissa, Erumere, Esther, Amlani, Sageet, Auld, Grace, Salek-Haddadi, Afraim, Schulz, Ursula, Kennedy, James, Ford, Gary, Mathieson, Philip, Reckless, Ian, Teal, Rachel, Lenti, Giulia, Harston, George, O'Brien, Eoin, Mcgee, Joanne, Mitchell, Jennifer, Amis, Elaine, Handley, Dominic, Kelly, Siobhan, Zachariah, George, Francis, Jobbin, Crisp, Sarah, Sesay, Juliana, Finlay, Sarah, Hayhoe, Helen, Hannon, Niamh, Hughes, Tom, Morse, Bethan, De Berker, Henry, Tallantyre, Emma, Osman, Ahmed, White, Susan, Schwarz, Stefan, Jelley, Benjamin, Yadava, Rajendra, Azhar, Khalid, Reddan, Julie, Sangombe, Mirriam, Stafford, Samantha, Fotherby, Ken, Morgan, Debbie, Baig, Farrukh, Jennings-Preece, Karla, Butler, Donna, Ahmad, Nasar, Willberry, Angela, Stevens, Angela, Rai, Baljinder, Siddegowda, Prasad, Howard, Peter, Saulat, Afaq, Hyatt, Lisa, Dobson, Tracey, Jarrett, David, Ponnambath, Suheil, Tandy, Jane, Harrington-Davies, Yasmin, Butler, Rebecca, James, Claire, Valentine, Stacey, Suttling, Anne, Langhorne, Peter, Kerr, Gillian, Wright, Fiona, Graham, Ruth, McAlpine, Christine, Iqbal, Mohammad Shahzad, Humphreys, Louise, Pasco, Kath, Balazikova, Olga, Nasim, Ashraf, Peixoto, Cassilda, Gallagher, Louise, Shahmehri, Shahrzad, Ghosh, Sandip, Barrie, Elizabeth, Gilmour, Danielle, Henry, Margo, Webb, Tom, Cowie, Linda, Rudenko, Hannah, McDonald, Shanni, Schumacher, Natasha, Walker, Susannah, Cosier, Tracey, Verrion, Anna, Beranova, Eva, Thomson, Audrey, Venter, Marius, Kar, Arindam, Mashate, Sheila, Harvey, Kirsten, Gardener, Léjeune, Nguyen, Vinh, Halse, Omid, Geraghty, Olivia, Hazel, Beth, Wilding, Peter, Tilley, Victoria, Esisi, Bernard, Cassidy, Tim, McClelland, Beverley, Bokhari, Maria, England, Timothy, Hedstrom, Amanda, Maddula, Mohana, Donnelly, Richard, Findlay, Paul, Macaden, Ashish, Shread, Ian, Barr, Charlotte, Mohd Nor, Azlisham, Brown, Claire, Persad, Nicola, Eglinton, Charlotte, Weinling, Marie, Hyams, Benjamin, Shah, Alex, Baker, John, Byrne, Anthony, McGhee, Caroline, Smart, Amanda, Copeland, Claire, Carpenter, Michael, Walker, Marion, Davey, Richard, Needle, Ann, Fathima, Razik, Bateman, Gavin, Datta, Prabal, Stanners, Andrew, Jackson, Linda, Ball, Julie, Davis, Michelle, Atkinson, Natalie, Fawcett, Michelle, Thompson, Teresa, Guy, Helen, Hogg, Valerie, Hays, Carole, Woodward, Stephen, Haque, Mohammad, Hakim, Eluzai, Symonds, Stuart, Maanoosi, Mehran, Herman, Jane, Black, Toby, Miriam, Skelton, Clarke, Caroline, Anthony, Alpha, Tribbeck, Michele, Cronin, Julie, Mead, Denise, Fennelly, Ruth, McIlmoyle, James, Dickinson, Christina, Jeffs, Carol, Anwar, Sajjad, Howard, Joanne, Jones, Kirsty, Dhar, Saikat, Clay, Caroline, Siddiq, Muhammad, Ivatts, Simone, Baird, Yolanda, Sally, Moore, Amey, Isobel, Newton, Sophie, Clayton-Evans, Lisa, Chadbourn, Indra, Rayessa, Rayessa, Naylor, Charde, Rodgers, Alicia, Wilson, Lisa, Wilson, Sarah, Clarkson, Emma, Davies, Ruth, Owings, Paula, Sangster, Graeme, Gott, Valerie, Little, Victoria, Weir, Pauline, Cherian, Suja, Jose, Deepa, Moroney, Helen, Downham, Susan, Dodd, Angela, Vettimootal Johnson, Venetia, Codd, Laura, Robinson, Naomi, Ahmed, Ashraf, Albazzaz, Mo, Johnson, Sharon, Denniss, Carol, Cunningham, Mishell, Zahoor, Tajammal, Webster, Timothy, Leason, Sandra, Haider, Syed, Chatterjee, Kausic, Nallasivan, Arumugam, Perkins, Charlotte, Seagrave, Samantha, Jenkins, Colin, Price, Fiona, Hughes, Claire, Mercer, Lily, Hussain, Malik, Brown, Sarah, Harvey, Miriam, Homan, Jane, Khan, Mohammad, Whiting, Robert, Foote, Leanne, Hunt, Nicholas, Durman, Helen, Brotherton, Lucy, Foot, Jayne, Pawley, Corinne, Foster, Eliza, Whitcher, Alison, Metcalf, Kneale, Jagger, Jenny, McDonald, Susan, Waterfield, Kelly, Sutton, Patrick, Shinh, Naval, Anversha, Ajmal, Ravenhill, Garth, Greenwood, Richard, Saada, Janak, Wiltshire, Alison, Perfitt, Rebekah, Andole, Sreeman, Gadapa, Naveen, Dunne, Karen, Krommyda, Magdalini, Burssens, Evelyne, King, Sam, Plewa, Catherine, Smyth, Nigel, Wilson, Jenny, Giallombardo, Elio, Eglinton, Charlotte, Sykes, Lucy, Kumar, Pradeep, Barker, James, Huggett, Isabel, Dunn, Linda, Culmsee, Charlotte, Thomas, Philip, Myint, Min, O'Brien, Richard, Brew, Helen, Majmudar, Nikhil, O'Connell, Janice, Bunea, George, Fox, Charlotte, Gulliver, Diane, Smith, Andrew, Mokoena, Betty, Sattar, Naweed, Krishnamurthy, Ramesh, Osborne, Emily, Wilson, David, Wroath, Belinda, Dynan, Kevin, Power, Michael, Thompson, Susan, Adell, Victoria, Orugun, Enoch, Poultney, Una, Glover, Rachel, Crowther, Hannah, Thornthwaite, Sarah, Wiggam, Ivan, Wallace, Aine, Kerr, Enda, Fulton, Ailsa, Hunter, Annemarie, Tauro, Suzanne, Cuddy, Sarah, Mangion, David, Hardwick, Anne, Markova, Skarlet, Lawrence, Tara, Constantin, Carmen, Fletcher, Jo, Thomas, Isobel, Pettitt, Kerry, Sekaran, Lakshmanan, Tate, Margaret, Bharaj, Kiranjit, Simon, Rohan, Justin, Frances, Sethuraman, Sakthivel, Phiri, Duke, Mohammed, Niaz, Chauhan, Meena, Elfandi, Khaled, Khan, Uzma, Stafford, Samantha, Reddan, Julie, Eveson, David, Mistri, Amit, Manning, Lisa, Khan, Shagufta, Patel, Champa, Moqsith, Mohammed, Sattar, Saira, Lam, Man Yee, Musarrat, Kashif, Stephens, Claire, Kalathil, Latheef, Miller, Richard, Salehin, Maqsud, Gautam, Nikki, Bailey, Duncan, Amor, Kelly, Meir, Julie, Nicolson, Anne, Imam, Javed, Wood, Lisa, White, Julie, Sajid, Mahmud, Ghaly, George, Ball, Margaret, Gascoyne, Rachel, Proeschel, Harald, Sharpe, Simon, Horton, Sarah, Beaves, Emily, Jones, Stephanie, Yip, Brigitte, Bell, Murdina, MacLiver, Linda, MacInnes, Brian, Esson, Derek, Sims, Don, Hurley, Jennifer, Willmot, Mark, Sutton, Claire, Littleton, Edward, Maiden, Susan, Jones, Rachael, Cunningham, James, Green, Carole, Bates, Michelle, Shekhar, Raj, Waterfield, Kelly, Gilham, Ellie, Ahmed, Iman, Crown, Rachel, Fuller, Tracy, Goorah, Neetish, Bell, Angela, Kelly, Christine, Singh, Arun, Walford, Jamie, Tomlinson, Benjamin, Patel, Farzana, Duberley, Stephen, Kane, Ingrid, Rajkumar, Chakravarthi, Gaylard, Jane, Breeds, Joanna, Gainsborough, Nicola, Pitt-Ford, Alexandra, Barbon, Emma, Latter, Laura, Thompson, Philip, Hervey, Simon, Krishnamoorthy, Shrivakumar, Vassallo, Joseph, Walter, Deborah, Cochrane, Helen, Srinivasan, Meena, Campbell, Robert, Donaldson, Denise, Motherwell, Nichola, Hurford, Frances, Mukherjee, Indranil, Kenton, Antony, Nyabadza, Sheila, Martin, Irene, Hunt, Benjamin, Hassan, Hardi, O'Toole, Sarah, Dallol, Bander, Putterill, Janet, Jha, Ratneshwari, Gallifent, Rachel, Kakar, Puneet, Pusalkar, Aparna, Chan, Kelly, Dangri, Puneet, Beadle, Hannah, Cook, Angela, Crabtree, Karen, Subramonian, Santhosh, Owusu-Agyei, Peter, Temple, Natalie, Butterworth-Cowin, Nicola, Ragab, Suzanne, Knops, Kerstin, Jinks, Emma, Dickson, Christine, Gleave, Laura, Dube, Judith, Leggett, Jacqui, Garcia, Tatiana, Ispoglou, Sissy, Evans, Rachel, Ankolekar, Sandeep, Hayes, Anne, Ni, Hlaing, Rahman, Bithi, Milligan, Josette, Graham, Carol, Jose, Josin, Keegan, Breffni, Doherty, Mandy, Kelly, Jim, Blair, Caroline, Dewar, Richard, White, James, and Thomas, Kelly

Abstract

Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events.

Published
2019
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14. Statin intolerance: an updated, narrative review mainly focusing on muscle adverse effects

Author

Li, Jian-Jun, Liu, Hui-Hui, Wu, Na-Qiong, Yeo, Khung Keong, Tan, Kathryn, Ako, Junya, Krittayaphong, Rungroj, Tan, Ru San, Aylward, Philip E, Baek, Sang Hong, Dalal, Jamshed, Fong, Alan Yean Yip, Li, Yi-Heng, O’Brien, Richard C, Lim, Tien Siang Eric, Koh, Si Ya Natalie, Scherer, Daniel J, Tada, Hayato, Kang, Vernon, Butters, Julie, and Nicholls, Stephen J

Abstract

ABSTRACTIntroductionStatins have been established as the standard of care for dyslipidemia and preventing cardiovascular diseases while posing few safety concerns. However, misconceptions about statin intolerance lead to their underuse, indicating a need to improve the understanding of the safety of this treatment.Areas coveredWe searched PubMed and reviewed literatures related to statin intolerance published between February 2015 and February 2020. Important large-scale or landmark studies published before 2015 were also cited as key evidence.Expert opinionOptimal lowering of low-density lipoprotein cholesterol with statins substantially reduces the risk of cardiovascular events. Muscle adverse events (AEs) were the most frequently reported AEs by statin users in clinical practice, but they usually occurred at a similar rate with statins and placebo in randomized controlled trials and had a spurious causal relationship with statin treatment. We proposed a rigorous definition for identifying true statin intolerance and present the criteria for defining different forms of muscle AEs and an algorithm for their management. True statin intolerance is uncommon, and every effort should be made to exclude false statin intolerance and ensure optimal use of statins. For the management of statin intolerance, statin-based approaches should be prioritized over non-statin approaches.

Published
2020
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15. Neuropathologic, genetic, and longitudinal cognitive profiles in primary age‐related tauopathy (PART) and Alzheimer's disease.

Author

Bell, W. Robert, An, Yang, Kageyama, Yusuke, English, Collin, Rudow, Gay L., Pletnikova, Olga, Thambisetty, Madhav, O'Brien, Richard, Moghekar, Abhay R., Albert, Marilyn S., Rabins, Peter V., Resnick, Susan M., and Troncoso, Juan C.

Abstract

Introduction: Primary age‐related tauopathy (PART) is a recently described entity that can cause cognitive impairment in the absence of Alzheimer's disease (AD). Here, we compared neuropathological features, tau haplotypes, apolipoprotein E (APOE) genotypes, and cognitive profiles in age‐matched subjects with PART and AD pathology. Methods: Brain autopsies (n = 183) were conducted on participants 85 years and older from the Baltimore Longitudinal Study of Aging and Johns Hopkins Alzheimer's Disease Research Center. Participants, normal at enrollment, were followed with periodic cognitive evaluations until death. Results: Compared with AD, PART subjects showed significantly slower rates of decline on measures of memory, language, and visuospatial performance. They also showed lower APOE ε4 allele frequency (4.1% vs. 17.6%, P =.0046). Discussion: Our observations suggest that PART is separate from AD and its distinction will be important for the clinical management of patients with cognitive impairment and for public health care planning. [ABSTRACT FROM AUTHOR]

Published
2019
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16. A prognostic model of Alzheimer's disease relying on multiple longitudinal measures and time‐to‐event data.

Author

Li, Kan, O'Brien, Richard, Lutz, Michael, and Luo, Sheng

Abstract

Introduction: Characterizing progression in Alzheimer's disease is critically important for early detection and targeted treatment. The objective was to develop a prognostic model, based on multivariate longitudinal markers, for predicting progression‐free survival in patients with mild cognitive impairment. Methods: The information contained in multiple longitudinal markers was extracted using multivariate functional principal components analysis and used as predictors in the Cox regression models. Cross‐validation was used for selecting the best model based on Alzheimer's Disease Neuroimaging Initiative–1. External validation was conducted on Alzheimer's Disease Neuroimaging Initiative–2. Results: Model comparison yielded a prognostic index computed as the weighted combination of historical information of five neurocognitive longitudinal markers that are routinely collected in observational studies. The comprehensive validity analysis provided solid evidence of the usefulness of the model for predicting Alzheimer's disease progression. Discussion: The prognostic model was improved by incorporating multiple longitudinal markers. It is useful for monitoring disease and identifying patients for clinical trial recruitment. Highlights: A novel and efficient statistical method for prognosis of progression‐free survival in mild cognitive impairment patients using multiple longitudinal markers.The prognostic model was evaluated via both internal and external validations.The longitudinal profiles of multiple markers, all of which are routinely collected in observational studies, could enhance the prognostic accuracy of Alzheimer's disease, if they are properly included in the prognostic model.A prognostic index produced by the prognostic model is useful for monitoring disease progression and identifying patients for clinical trial recruitment. [ABSTRACT FROM AUTHOR]

Published
2018
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17. Evidence for brain glucose dysregulation in Alzheimer's disease.

Author

An, Yang, Varma, Vijay R., Varma, Sudhir, Casanova, Ramon, Dammer, Eric, Pletnikova, Olga, Chia, Chee W., Egan, Josephine M., Ferrucci, Luigi, Troncoso, Juan, Levey, Allan I., Lah, James, Seyfried, Nicholas T., Legido‐Quigley, Cristina, O'Brien, Richard, and Thambisetty, Madhav

Abstract

Introduction: It is unclear whether abnormalities in brain glucose homeostasis are associated with Alzheimer's disease (AD) pathogenesis. Methods: Within the autopsy cohort of the Baltimore Longitudinal Study of Aging, we measured brain glucose concentration and assessed the ratios of the glycolytic amino acids, serine, glycine, and alanine to glucose. We also quantified protein levels of the neuronal (GLUT3) and astrocytic (GLUT1) glucose transporters. Finally, we assessed the relationships between plasma glucose measured before death and brain tissue glucose. Results: Higher brain tissue glucose concentration, reduced glycolytic flux, and lower GLUT3 are related to severity of AD pathology and the expression of AD symptoms. Longitudinal increases in fasting plasma glucose levels are associated with higher brain tissue glucose concentrations. Discussion: Impaired glucose metabolism due to reduced glycolytic flux may be intrinsic to AD pathogenesis. Abnormalities in brain glucose homeostasis may begin several years before the onset of clinical symptoms. Highlights: Brain tissue glucose is associated with severity of Alzheimer's disease (AD) pathology and symptom onset.Reduced brain glycolytic flux is associated with severity of AD pathology and symptom onset.Neuronal glucose transporter‐3 is lower in AD.Lower glucose transporter‐3 levels are associated with more severe AD pathology.Increase in plasma glucose decades before death is related to higher brain glucose. [ABSTRACT FROM AUTHOR]

Published
2018
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18. Community and Conflict: A Practitioner's Perspective on Verse Drama.

Author

O'BRIEN, RICHARD

Subjects
VERSE drama, CREATIVE writing, EXCEPTIONALISM (Political science)
Abstract

The article offers the author's insights on the portrayal of verse drama in the own creative practice of a writer. He explores scripts from three novels such as "Free for All," "Sanctuary," and "The Vetting of Kit Shaughnessy." He cites the impacts of the work of playwright William Shakespeare on the treatment of verse drama in contemporary culture and exceptionalism, which he considers to restrict the expression by creative artists.

Published
2018

21. Closed Doors.

Author

O'Brien, Richard

Subjects
CLOSED Doors (Poem), O'BRIEN, Richard
Published
2018

23. Stuck between a referral and a hard place.

Author

O’Brien, Richard, Li, Joe, and Muir, James

Abstract

The article offers information on the challenges faced by specialists and general practitioners regarding Medicare regulations and referral practices.

Published
2023

24. Zinc transporter 8 haploinsufficiency protects against beta cell dysfunction in type 1 diabetes by increasing mitochondrial respiration.

Author

Kim, Yong Kyung, Walters, Jay A., Moss, Nicole D., Wells, Kristen L., Sheridan, Ryan, Miranda, Jose G., Benninger, Richard K.P., Pyle, Laura L., O'Brien, Richard M., Sussel, Lori, and Davidson, Howard W.

Abstract

Zinc transporter 8 (ZnT8) is a major humoral target in human type 1 diabetes (T1D). Polymorphic variants of Slc30A8 , which encodes ZnT8, are also associated with protection from type 2 diabetes (T2D). The current study examined whether ZnT8 might play a role beyond simply being a target of autoimmunity in the pathophysiology of T1D. The phenotypes of NOD mice with complete or partial global loss of ZnT8 were determined using a combination of disease incidence, histological, transcriptomic, and metabolic analyses. Unexpectedly, while complete loss of ZnT8 accelerated spontaneous T1D, heterozygosity was partially protective. In vivo and in vitro studies of ZnT8 deficient NOD.SCID mice suggested that the accelerated disease was due to more rampant autoimmunity. Conversely, beta cells in heterozygous animals uniquely displayed increased mitochondrial fitness under mild proinflammatory conditions. In pancreatic beta cells and immune cell populations, Zn2+ plays a key role as a regulator of redox signaling and as an independent secondary messenger. Importantly, Zn2+ also plays a major role in maintaining mitochondrial homeostasis. Our results suggest that regulating mitochondrial fitness by altering intra-islet zinc homeostasis may provide a novel mechanism to modulate T1D pathophysiology. • NOD. ZnT8−/− animals get accelerated spontaneous type 1 diabetes. • NOD. ZnT8+/− animals are partially protected from spontaneous type 1 diabetes. • Beta cell mitochondrial fitness is potentiated in NOD. ZnT8+/− animals exposed to low doses of pro-inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Published
2022
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26. Opposite associations between alanine aminotransferase and γ-glutamyl transferase levels and all-cause mortality in type 2 diabetes: Analysis of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

Author

Williams, Kathryn H., Sullivan, David R., Nicholson, Geoffrey C., George, Jacob, Jenkins, Alicia J., Januszewski, Andrzej S., Gebski, Val J., Manning, Patrick, Tan, Yong Mong, Donoghoe, Mark W., Ehnholm, Christian, Young, Simon, O'Brien, Richard, Buizen, Luke, Twigg, Stephen M., and Keech, Anthony C.

Subjects
ALANINE aminotransferase, TYPE 2 diabetes, TRANSFERASES, FENOFIBRATE, LIVER enzymes, DISEASE prevalence
Abstract

Aims Reported associations between liver enzymes and mortality may not hold true in type 2 diabetes, owing to a high prevalence of non-alcoholic fatty liver disease, which has been linked to cardiovascular disease and mortality in its own right. Our study aimed to determine whether alanine aminotransferase (ALT) or γ-glutamyl transferase (GGT) levels predict mortality in type 2 diabetes, and to examine possible mechanisms. Methods Data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study were analyzed to examine the relationship between liver enzymes and all-cause and cause-specific mortality over 5 years. Results Over 5 years, 679 (6.9%) individuals died. After adjustment, for every standard deviation increase in ALT (13.2 U/L), the HR for death on study was 0.85 (95% CI 0.78–0.93), p < 0.001. Conversely, GGT > 70 U/L, compared with GGT ≤ 70 U/L, had HR 1.82 (1.48–2.24), p < 0.001. For cause-specific mortality, lower ALT was associated with a higher risk of cardiovascular death only, whereas GGT > 70 U/L was associated with higher risks of death due to cardiovascular disease, cancer and non-cancer/non-cardiovascular causes. The relationship for ALT persisted after adjustment for indirect measures of frailty but was attenuated by elevated hsCRP. Conclusions As in the general population, ALT has a negative, and GGT a positive, correlation with mortality in type 2 diabetes when ALT is less than two times the upper limit of normal. The relationship for ALT appears specific for death due to cardiovascular disease. Links of low ALT with frailty, as a potential mechanism for relationships seen, were neither supported nor conclusively refuted by our analysis and other factors are also likely to be important in those with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Published
2016
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30. Combined Deletion of Slc30a7and Slc30a8Unmasks a Critical Role for ZnT8 in Glucose-Stimulated Insulin Secretion

Author

Syring, Kristen E., Boortz, Kayla A., Oeser, James K., Ustione, Alessandro, Platt, Kenneth A., Shadoan, Melanie K., McGuinness, Owen P., Piston, David W., Powell, David R., and O'Brien, Richard M.

Abstract

Polymorphisms in the SLC30A8gene, which encodes the ZnT8 zinc transporter, are associated with altered susceptibility to type 2 diabetes (T2D), and SLC30A8haploinsufficiency is protective against the development of T2D in obese humans. SLC30A8is predominantly expressed in pancreatic islet β-cells, but surprisingly, multiple knockout mouse studies have shown little effect of Slc30a8deletion on glucose tolerance or glucose-stimulated insulin secretion (GSIS). Multiple other Slc30aisoforms are expressed at low levels in pancreatic islets. We hypothesized that functional compensation by the Slc30a7isoform, which encodes ZnT7, limits the impact of Slc30a8deletion on islet function. We therefore analyzed the effect of Slc30a7deletion alone or in combination with Slc30a8on in vivo glucose metabolism and GSIS in isolated islets. Deletion of Slc30a7alone had complex effects in vivo, impairing glucose tolerance and reducing the glucose-stimulated increase in plasma insulin levels, hepatic glycogen levels, and pancreatic insulin content. Slc30a7deletion also affected islet morphology and increased the ratio of islet α- to β-cells. However, deletion of Slc30a7alone had no effect on GSIS in isolated islets, whereas combined deletion of Slc30a7and Slc30a8abolished GSIS. These data demonstrate that the function of ZnT8 in islets can be unmasked by removal of ZnT7 and imply that ZnT8 may affect T2D susceptibility through actions in other tissues where it is expressed at low levels rather than through effects on pancreatic islet function.

Published
2016
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32. G6PC2 Modulates the Effects of Dexamethasone on Fasting Blood Glucose and Glucose Tolerance

Author

Boortz, Kayla A., Syring, Kristen E., Lee, Rebecca A., Dai, Chunhua, Oeser, James K., McGuinness, Owen P., Wang, Jen-Chywan, and O'Brien, Richard M.

Abstract

The glucose-6-phosphatase catalytic subunit 2 (G6PC2) gene encodes an islet-specific glucose-6-phosphatase catalytic subunit. G6PC2 forms a substrate cycle with glucokinase that determines the glucose sensitivity of insulin secretion. Consequently, deletion of G6pc2lowers fasting blood glucose (FBG) without affecting fasting plasma insulin. Although chronic elevation of FBG is detrimental to health, glucocorticoids induce G6PC2expression, suggesting that G6PC2 evolved to transiently modulate FBG under conditions of glucocorticoid-related stress. We show, using competition and mutagenesis experiments, that the synthetic glucocorticoid dexamethasone (Dex) induces G6PC2promoter activity through a mechanism involving displacement of the islet-enriched transcription factor MafA by the glucocorticoid receptor. The induction of G6PC2promoter activity by Dex is modulated by a single nucleotide polymorphism, previously linked to altered FBG in humans, that affects FOXA2 binding. A 5-day repeated injection paradigm was used to examine the chronic effect of Dex on FBG and glucose tolerance in wild-type (WT) and G6pc2knockout mice. Acute Dex treatment only induces G6pc2expression in 129SvEv but not C57BL/6J mice, but this chronic treatment induced G6pc2expression in both. In 6-hour fasted C57BL/6J WT mice, Dex treatment lowered FBG and improved glucose tolerance, with G6pc2deletion exacerbating the decrease in FBG and enhancing the improvement in glucose tolerance. In contrast, in 24-hour fasted C57BL/6J WT mice, Dex treatment raised FBG but still improved glucose tolerance, with G6pc2deletion limiting the increase in FBG and enhancing the improvement in glucose tolerance. These observations demonstrate that G6pc2 modulates the complex effects of Dex on both FBG and glucose tolerance.

Published
2016
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33. G6PC2 Modulates Fasting Blood Glucose In Male Mice in Response to Stress

Author

Boortz, Kayla A., Syring, Kristen E., Dai, Chunhua, Pound, Lynley D., Oeser, James K., Jacobson, David A., Wang, Jen-Chywan, McGuinness, Owen P., Powers, Alvin C., and O'Brien, Richard M.

Abstract

The glucose-6-phosphatase catalytic 2 (G6PC2) gene is expressed specifically in pancreatic islet beta cells. Genome-wide association studies have shown that single nucleotide polymorphisms in the G6PC2gene are associated with variations in fasting blood glucose (FBG) but not fasting plasma insulin. Molecular analyses examining the functional effects of these single nucleotide polymorphisms demonstrate that elevated G6PC2expression is associated with elevated FBG. Studies in mice complement these genome-wide association data and show that deletion of the G6pc2gene lowers FBG without affecting fasting plasma insulin. This suggests that, together with glucokinase, G6PC2 forms a substrate cycle that determines the glucose sensitivity of insulin secretion. Because genome-wide association studies and mouse studies demonstrate that elevated G6PC2expression raises FBG and because chronically elevated FBG is detrimental to human health, increasing the risk of type 2 diabetes, it is unclear why G6PC2 evolved. We show here that the synthetic glucocorticoid dexamethasone strongly induces human G6PC2promoter activity and endogenous G6PC2expression in isolated human islets. Acute treatment with dexamethasone selectively induces endogenous G6pc2expression in 129SvEv but not C57BL/6J mouse pancreas and isolated islets. The difference is due to a single nucleotide polymorphism in the C57BL/6J G6pc2promoter that abolishes glucocorticoid receptor binding. In 6-hour fasted, nonstressed 129SvEv mice, deletion of G6pc2lowers FBG. In response to the stress of repeated physical restraint, which is associated with elevated plasma glucocorticoid levels, G6pc2gene expression is induced and the difference in FBG between wild-type and knockout mice is enhanced. These data suggest that G6PC2 may have evolved to modulate FBG in response to stress.

Published
2016
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34. Hypothetical Preclinical Alzheimer Disease Groups and Longitudinal Cognitive Change

Author

Soldan, Anja, Pettigrew, Corinne, Cai, Qing, Wang, Mei-Cheng, Moghekar, Abhay R., O’Brien, Richard J., Selnes, Ola A., and Albert, Marilyn S.

Abstract

IMPORTANCE: Clinical trials testing treatments for Alzheimer disease (AD) are increasingly focused on cognitively normal individuals in the preclinical phase of the disease. To optimize observing a treatment effect, such trials need to enroll cognitively normal individuals likely to show cognitive decline over the duration of the trial. OBJECTIVE: To identify which group of cognitively normal individuals shows the greatest cognitive decline over time based on their cerebrospinal fluid biomarker profile. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, cognitively normal participants were classified into 1 of the following 4 hypothetical preclinical AD groups using baseline cerebrospinal fluid levels of Aβ and tau or Aβ and phosphorylated tau (p-tau): stage 0 (high Aβ and low tau), stage 1 (low Aβ and low tau), stage 2 (low Aβ and high tau), and suspected non-AD pathology (SNAP) (high Aβ and high tau). The data presented herein were collected between August 1995 and August 2014. MAIN OUTCOMES AND MEASURES: An a priori cognitive composite score based on the following 4 tests previously shown to predict progression from normal cognition to symptom onset of mild cognitive impairment or dementia: Paired Associates immediate recall, Logical Memory delayed recall, Boston Naming, and Digit-Symbol Substitution. Linear mixed-effects models were used to compare the cognitive composite scores across the 4 groups over time, adjusting for baseline age, sex, education, and their interactions with time. RESULTS: Two hundred twenty-two cognitively normal participants were included in the analyses (mean follow-up, 11.0 years [range, 0-18.3 years] and mean baseline age, 56.9 years [range, 22.1-85.8 years]). Of these, 102 were stage 0, 46 were stage 1, 28 were stage 2, and 46 were SNAP. Individuals in stage 2 (low Aβ and high tau [or p-tau]) had lower baseline cognitive scores and a greater decline in the cognitive composite score relative to the other 3 groups (β ≤ −0.06 for all and P ≤ .001 for the rate of decline for all). Individuals in stage 0, stage 1, and SNAP did not differ from one another in cognitive performance at baseline or over time (11.0 years) and showed practice-related improvement in performance. The APOE ε4 genotype was not associated with baseline cognitive composite score or the rate of change in the cognitive composite score. CONCLUSIONS AND RELEVANCE: These results suggest that, to optimize observing a treatment effect, clinical trials enrolling cognitively normal individuals should selectively recruit participants with abnormal levels of both amyloid and tau (ie, stage 2) because this group would be expected to show the greatest cognitive decline over time if untreated.

Published
2016
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35. Personality and risk of Alzheimer's disease: New data and meta-analysis.

Author

Terracciano, Antonio, Sutin, Angelina R., An, Yang, O'Brien, Richard J., Ferrucci, Luigi, Zonderman, Alan B., and Resnick, Susan M.

Abstract

Abstract: Background: We examine whether broad factors and specific facets of personality are associated with increased risk of incident Alzheimer's disease (AD) in a long-run longitudinal study and a meta-analysis of published studies. Methods: Participants (n = 1671) were monitored for up to 22 years from a baseline personality assessment. The meta-analysis pooled results from up to five prospective studies (n = 5054). Results: Individuals with scores in the top quartile of neuroticism (hazard ratio = 3.1; 95% confidence interval = 1.6–6.0) or the lowest quartile of conscientiousness (hazard ratio = 3.3; 95% confidence interval = 1.4–7.4) had a threefold increased risk of incident AD. Among the components of these traits, self-discipline and depression had the strongest associations with incident AD. The meta-analysis confirmed the associations of neuroticism (P = 2 × 10−9) and conscientiousness (P = 2 × 10−6), along with weaker effects for openness and agreeableness (P < .05). Conclusions: The current study and meta-analysis indicate that personality traits are associated with increased risk of AD, with effect sizes similar to those of well-established clinical and lifestyle risk factors. [Copyright &y& Elsevier]

Published
2014
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37. Porous Solids Impregnated with Task-Specific Ionic Liquids as Composite Sorbents

Author

Ruckart, K. Neil, O’Brien, Richard A., Woodard, Seth M., West, Kevin N., and Glover, T. Grant

Abstract

This work examines six task-specific ionic liquids (TSILs), comprised of the taurinate anion paired with five tetraalkylammonium cations (where alkyl = methyl, ethyl, propyl, butyl, and hexyl) and a tetrabutylphosphonium cation, impregnated in ordered mesoporous silica, SBA-15. The composites showed significantly increased CO2uptakes relative to the parent SBA-15 materials. The surface area of these materials varies from approximately 5 to 1000 m2/g depending on the amount of IL loaded into the silica pores. The presence of n-hexyl side chains on the TSIL significantly reduces water loading, indicating that judicious IL selection may provide a means of controlling water uptake. After exposure to water vapor, three of the six cation-taurinate composites displayed an increase in CO2capacity. X-ray diffraction data of the composite of tetramethylammonium taurinate and SBA-15 shows that the ionic liquid is crystalline inside the pores of the silica. Isotherms are measured at several different temperatures and the results show that storage at ambient humidity significantly impacts the capacity of these materials. By comparison, the TSILs supported on an amorphous porous support, BPL activated carbon, showed no increase in CO2adsorption capacity. The results provide physical insight into the synthesis, structure, porosity, and sorption capacity of composites of adsorbents and ionic liquids that need to be considered prior to application.

Published
2015
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42. Laboratory technique for coloring titanium abutments to improve esthetics.

Author

Wadhwani, Chandur P.K., O’Brien, Richard, Kattadiyil, Mathew T., and Chung, Kwok-Hung

Abstract

Titanium alloys are used for implant abutments onto which prostheses are attached. One major disadvantage of titanium abutments is their esthetics; the metallic gray color may show through the restorative material or through surrounding tissues. A laboratory technique using readily available household items is described that can alter the abutment color by anodization. [ABSTRACT FROM AUTHOR]

Published
2016
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43. Tunnel School

Author

Brenner, Brian, O'Brien, Richard, Brenner, Brian, and O'Brien, Richard

Abstract

As part of a session during Engineer's Week, a class was prepared for highschool students. The session was organized on behalf of the public outreach program on the Central Artery/Tunnel (CA/T) project, in Boston. During the hourlong class, students received an introduction to the project, a discussion about how civil engineers and planners perform their work. They were then challenged with a homework problem based on an actual design condition from the project. The class concluded with a discussion of practical steps to be taken to go from being a student to being a practicing engineer. The class was modified for presentation to college and grammarschool students. The class can serve as an example of a way practicing engineers can contribute to the education of schoolage future engineers.

Published
1994
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44. The Coronation of Queen Elizabeth II.

Author

O'Brien, Richard S.

Subjects
HISTORY of television broadcasting, CORONATIONS
Abstract

Recalls the Columbia Broadcasting System Television network's recording of the British Broadcasting Co.'s broadcast of the Coronation of Queen Elizabeth II for rebroadcast in the U.S. on June 2, 1953. Use of the GPL video-recording monitor and the GPL rapid processing unit; Problems encountered by the television engineers; Test flight of the editing facilities installed in the British Overseas Airways Corp. Stratocruiser.

Published
2004
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46. Relationship of cognitive reserve and APOE status to the emergence of clinical symptoms in preclinical Alzheimer’s disease

Author

Pettigrew, Corinne, Soldan, Anja, Li, Shanshan, Lu, Yi, Wang, Mei-Cheng, Selnes, Ola A., Moghekar, Abhay, O’Brien, Richard, and Albert, Marilyn

Abstract

The APOE ε4 allele increases the risk of developing Alzheimer’s disease, whereas the APOE ε2 allele reduces risk. We examined whether cognitive reserve (CR), as measured by an index consisting of education, reading, and vocabulary, modifies these associations. CR was measured at baseline in 257 cognitively normal individuals (mean age 57.2 years) who have been followed for up to 17 years (mean follow-up = 9.2 years). Cox regression models showed that CR and APOE ε4 independently affected the risk of progressing from normal cognition to onset of clinical symptoms: CR reduced risk by about 50% in both ε4 carriers and non-carriers, while ε4 increased risk by about 150%. In contrast, APOE ε2 interacted with CR, such that CR was more protective in ε2 carriers than non-carriers. This suggests that individuals with an ε2 genotype may disproportionately benefit from lifetime experiences that enhance cognition.

Published
2013
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47. CSF biomarker changes precede symptom onset of mild cognitive impairment

Author

Moghekar, Abhay, Li, Shanshan, Lu, Yi, Li, Ming, Wang, Mei-Cheng, Albert, Marilyn, and O’Brien, Richard

Abstract

This study evaluated longitudinal CSF biomarker measures collected when participants were cognitively normal to determine the magnitude and time course of biomarker changes before the onset of clinical symptoms in subjects with mild cognitive impairment (MCI).

Published
2013
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48. Glucose Intolerance, Insulin Resistance, and Pathological Features of Alzheimer Disease in the Baltimore Longitudinal Study of Aging

Author

Thambisetty, Madhav, Metter, E. Jeffrey, Yang, An, Dolan, Hillary, Marano, Christopher, Zonderman, Alan B., Troncoso, Juan C., Zhou, Yun, Wong, Dean F., Ferrucci, Luigi, Egan, Josephine, Resnick, Susan M., and O’Brien, Richard J.

Abstract

IMPORTANCE Peripheral glucose homeostasis has been implicated in the pathogenesis of Alzheimer disease (AD). The relationship among diabetes mellitus, insulin, and AD is an important area of investigation. However, whether cognitive impairment seen in those with diabetes is mediated by excess pathological features of AD or other related abnormalities, such as vascular disease, remains unclear. OBJECTIVE To investigate the association between serial measures of glucose intolerance and insulin resistance and in vivo brain β-amyloid burden, measured with carbon 11–labeled Pittsburgh Compound B (11C-PiB), and AD pathology at autopsy. DESIGN Scores calculated from the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) and Braak criteria were correlated with measures of hyperglycemia, hyperinsulinemia, glucose intolerance, and insulin resistance in 197 participants who underwent autopsy after death and who had undergone 2 or more oral glucose tolerance tests (OGTT) using grouped analyses and a continuous mixed-models analysis. The same measures of glucose intolerance and insulin resistance were also correlated with brain 11C-PiB retention in an additional 53 living subjects from the Baltimore Longitudinal Study of Aging neuroimaging study. SETTING Prospective, serially assessed cohort of community-dwelling subjects. PARTICIPANTS Cohort 1 consisted of 197 participants enrolled in the Baltimore Longitudinal Study of Aging who had 2 or more OGTTs during life and a complete brain autopsy after death. Cohort 2 consisted of 53 living subjects who had 2 or more OGTTs and underwent brain 11C-PiB positron emission tomography. EXPOSURES Autopsy and 11C-PiB positron emission tomography. MAIN OUTCOMES AND MEASURES The correlation of brain markers of AD, including CERAD score, Braak score, and 11C-PiB retention, with serum markers of glucose homeostasis using grouped and continuous mixed-models analyses. RESULTS We found no significant correlations between measures of brain AD pathology or 11C-PiB β-amyloid load and glucose intolerance or insulin resistance in subjects who had a mean (SD) of 6.4 (3.2) OGTTs during 22.1 (8.0) years of follow-up. Thirty subjects with frank diabetes mellitus who received medications also had AD pathology scores that were similar to those of the cohort as a whole. CONCLUSIONS AND RELEVANCE In this prospective cohort with multiple assessments of glucose intolerance and insulin resistance, measures of glucose and insulin homeostasis are not associated with AD pathology and likely play little role in AD pathogenesis. Long-term therapeutic trials are important to elucidate this issue.

Published
2013
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49. Multicenter Evaluation of Genechip for Detection of Multidrug-Resistant Mycobacterium tuberculosis

Author

Pang, Yu, Xia, Hui, Zhang, Zhiying, Li, Junchen, Dong, Yi, Li, Qiang, Ou, Xichao, Song, Yuanyuan, Wang, Yufeng, O'Brien, Richard, Kam, Kai Man, Chi, Junying, Huan, Shitong, Chin, Daniel P., and Zhao, Yanlin

Abstract

ABSTRACTDrug-resistant tuberculosis (TB), especially multidrug-resistant TB (MDR-TB), is still one of the most serious threats to TB control worldwide. Early diagnosis of MDR-TB is important for effectively blocking transmission and establishing an effective protocol for chemotherapy. Genechip is a rapid diagnostic method based on molecular biology that overcomes the poor biosafety, time consumption, and other drawbacks of traditional drug sensitivity testing (DST) that can detect MDR-TB. However, the Genechip approach has not been effectively evaluated, especially in limited-resource laboratories. In this study, we evaluated the performance of Genechip for MDR-TB in 1,814 patients in four prefectural or municipal laboratories and compared its performance with that of traditional DST. The results showed that the sensitivity and specificity of Genechip were 87.56% and 97.95% for rifampin resistance and 80.34% and 95.82% for isoniazid resistance, respectively. In addition, we found that the positive grade of the sputum smears influenced the judgment of results by Genechip. The test judged only 75% of the specimens of “scanty” positive grade. However, the positive grade of the specimens showed no influence on the accuracy of Genechip. Overall, the study suggests that, in limited-resource laboratories, Genechip showed high sensitivity and specificity for rifampin and isoniazid resistance, making it a more effective, rapid, safe, and cost-beneficial method worthy of broader use in limited-resource laboratories in China.

Published
2013
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