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1. Roadmap to fault tolerant quantum computation using topological qubit arrays

Author

Aasen, David, Aghaee, Morteza, Alam, Zulfi, Andrzejczuk, Mariusz, Antipov, Andrey, Astafev, Mikhail, Avilovas, Lukas, Barzegar, Amin, Bauer, Bela, Becker, Jonathan, Bello-Rivas, Juan M., Bhaskar, Umesh, Bocharov, Alex, Boddapati, Srini, Bohn, David, Bommer, Jouri, Bonderson, Parsa, Borovsky, Jan, Bourdet, Leo, Boutin, Samuel, Brown, Tom, Campbell, Gary, Casparis, Lucas, Chakravarthi, Srivatsa, Chao, Rui, Chapman, Benjamin J., Chatoor, Sohail, Christensen, Anna Wulff, Codd, Patrick, Cole, William, Cooper, Paul, Corsetti, Fabiano, Cui, Ajuan, van Dam, Wim, Dandachi, Tareq El, Daraeizadeh, Sahar, Dumitrascu, Adrian, Ekefjärd, Andreas, Fallahi, Saeed, Galletti, Luca, Gardner, Geoff, Gatta, Raghu, Gavranovic, Haris, Goulding, Michael, Govender, Deshan, Griggio, Flavio, Grigoryan, Ruben, Grijalva, Sebastian, Gronin, Sergei, Gukelberger, Jan, Haah, Jeongwan, Hamdast, Marzie, Hansen, Esben Bork, Hastings, Matthew, Heedt, Sebastian, Ho, Samantha, Hogaboam, Justin, Holgaard, Laurens, Van Hoogdalem, Kevin, Indrapiromkul, Jinnapat, Ingerslev, Henrik, Ivancevic, Lovro, Jablonski, Sarah, Jensen, Thomas, Jhoja, Jaspreet, Jones, Jeffrey, Kalashnikov, Kostya, Kallaher, Ray, Kalra, Rachpon, Karimi, Farhad, Karzig, Torsten, Kimes, Seth, Kliuchnikov, Vadym, Kloster, Maren Elisabeth, Knapp, Christina, Knee, Derek, Koski, Jonne, Kostamo, Pasi, Kuesel, Jamie, Lackey, Brad, Laeven, Tom, Lai, Jeffrey, de Lange, Gijs, Larsen, Thorvald, Lee, Jason, Lee, Kyunghoon, Leum, Grant, Li, Kongyi, Lindemann, Tyler, Lucas, Marijn, Lutchyn, Roman, Madsen, Morten Hannibal, Madulid, Nash, Manfra, Michael, Markussen, Signe Brynold, Martinez, Esteban, Mattila, Marco, Mattinson, Jake, McNeil, Robert, Mei, Antonio Rodolph, Mishmash, Ryan V., Mohandas, Gopakumar, Mollgaard, Christian, de Moor, Michiel, Morgan, Trevor, Moussa, George, Narla, Anirudh, Nayak, Chetan, Nielsen, Jens Hedegaard, Nielsen, William Hvidtfelt Padkær, Nolet, Frédéric, Nystrom, Mike, O'Farrell, Eoin, Otani, Keita, Paetznick, Adam, Papon, Camille, Paz, Andres, Petersson, Karl, Petit, Luca, Pikulin, Dima, Pons, Diego Olivier Fernandez, Quinn, Sam, Rajpalke, Mohana, Ramirez, Alejandro Alcaraz, Rasmussen, Katrine, Razmadze, David, Reichardt, Ben, Ren, Yuan, Reneris, Ken, Riccomini, Roy, Sadovskyy, Ivan, Sainiemi, Lauri, Saldaña, Juan Carlos Estrada, Sanlorenzo, Irene, Schaal, Simon, Schmidgall, Emma, Sfiligoj, Cristina, da Silva, Marcus P., Sinha, Sarat, Soeken, Mathias, Sohr, Patrick, Stankevic, Tomas, Stek, Lieuwe, Strøm-Hansen, Patrick, Stuppard, Eric, Sundaram, Aarthi, Suominen, Henri, Suter, Judith, Suzuki, Satoshi, Svore, Krysta, Teicher, Sam, Thiyagarajah, Nivetha, Tholapi, Raj, Thomas, Mason, Tom, Dennis, Toomey, Emily, Tracy, Josh, Troyer, Matthias, Turley, Michelle, Turner, Matthew D., Upadhyay, Shivendra, Urban, Ivan, Vaschillo, Alexander, Viazmitinov, Dmitrii, Vogel, Dominik, Wang, Zhenghan, Watson, John, Webster, Alex, Weston, Joseph, Williamson, Timothy, Winkler, Georg W., van Woerkom, David J., Wütz, Brian Paquelet, Yang, Chung Kai, Yu, Richard, Yucelen, Emrah, Zamorano, Jesús Herranz, Zeisel, Roland, Zheng, Guoji, Zilke, Justin, and Zimmerman, Andrew

Subjects
Quantum Physics, Condensed Matter - Superconductivity
Abstract

We describe a concrete device roadmap towards a fault-tolerant quantum computing architecture based on noise-resilient, topologically protected Majorana-based qubits. Our roadmap encompasses four generations of devices: a single-qubit device that enables a measurement-based qubit benchmarking protocol; a two-qubit device that uses measurement-based braiding to perform single-qubit Clifford operations; an eight-qubit device that can be used to show an improvement of a two-qubit operation when performed on logical qubits rather than directly on physical qubits; and a topological qubit array supporting lattice surgery demonstrations on two logical qubits. Devices that enable this path require a superconductor-semiconductor heterostructure that supports a topological phase, quantum dots and coupling between those quantum dots that can create the appropriate loops for interferometric measurements, and a microwave readout system that can perform fast, low-error single-shot measurements. We describe the key design components of these qubit devices, along with the associated protocols for demonstrations of single-qubit benchmarking, Clifford gate execution, quantum error detection, and quantum error correction, which differ greatly from those in more conventional qubits. Finally, we comment on implications and advantages of this architecture for utility-scale quantum computation., Comment: 11+6 pages, 8+5 figures

Published
2025

2. Experiences with Medications for Addiction Treatment Among Emergency Department Patients with Opioid Use Disorder

Author

Goldfine, Charlotte E., Chapman, Brittany P., Taylor, Melissa M., Bradley, Evan S., Carreiro, Stephanie P., Rosen, Rochelle R., Babu, Kavita M., and Lai, Jeffrey T.

Subjects
opioid-related disorders, substance withdrawal, naltrexone, buprenorphine, methadone
Abstract

Introduction: Medications for addiction treatment (MAT) are the evidence-based standard of care for treatment of opioid use disorder (OUD), but stigma continues to surround their use. We conducted an exploratory study to characterize perceptions of different types of MAT among people who use drugs.Methods: We conducted this qualitative study in adults with a history of non-medical opioid use who presented to an emergency department for complications of OUD. A semi-structured interview that explored knowledge, perceptions, and attitudes toward MAT was administered, and applied thematic analysis conducted.Results: We enrolled 20 adults. All participants had prior experience with MAT. Among participants indicating a preferred treatment modality, buprenorphine was the commonly favored agent. Previous experience with prolonged withdrawal symptoms upon MAT discontinuation and the perception of “trading one drug for another” were common reasons for reluctance to engage in agonist or partial-agonist therapy. While some participants preferred treatment with naltrexone, others were unwilling to initiate antagonist therapy due to fear of precipitated withdrawal. Most participants strongly considered the aversive nature of MAT discontinuation as a barrier to initiating treatment. Participants overall viewed MAT positively, but many had strong preferences for a particular agent.Conclusion: The anticipation of withdrawal symptoms during initiation and cessation of treatment affected willingness to engage in a specific therapy. Future educational materials for people who use drugs may focus on comparisons of respective benefits and drawbacks of agonists, partial agonists, and antagonists. Emergency clinicians must be prepared to answer questions about MAT discontinuation to effectively engage patients with OUD.

Published
2023

3. Nobody Wants to Be Narcan’d: A Pilot Qualitative Analysis of Drug Users’ Perspectives on Naloxone

Author

Lai, Jeffrey T., Goldfine, Charlotte E., Chapman, Brittany P., Taylor, Melissa M., Rosen, Rochelle K., Carreiro, Stephanie P., and Babu, Kavita M.

Subjects
Naloxone, Narcan, Substance-related disorders, Opioid overdose, Opioid use
Abstract

Introduction: Bystander naloxone distribution is an important component of public health initiatives to decrease opioid-related deaths. While there is evidence supporting naloxone distribution programs, the effects of increasing naloxone availability on the behavior of people who use drugs have not been adequately delineated. In this study we sought to 1) evaluate whether individuals’ drug use patterns have changed due to naloxone availability; and 2) explore individuals’ knowledge of, access to, experiences with, and perceptions of naloxone.Methods: We conducted a pilot study of adults presenting to the emergency department whose medical history included non-medical opioid use. Semi-structured interviews were conducted with participants and thematic analysis was used to code and analyze interview transcripts.Results: Ten participants completed the study. All were aware of naloxone by brand name (Narcan) and had been trained in its use, and all but one had either currently or previously possessed a kit. Barriers to naloxone administration included fear of legal repercussions, not having it available, and a desire to avoid interrupting another user’s “high.” Of the eight participants who reported being revived with naloxone at least once during their lifetime, all described experiencing a noxious physical response and expressed a desire to avoid receiving it again. Furthermore, participants did not report increasing their use of opioids when naloxone was available.Conclusions: Participants were accepting of and knowledgeable about naloxone, and were willing to administer naloxone to save a life. Participants tended to use opioids more cautiously when naloxone was present due to fears of experiencing precipitated withdrawal. This study provides preliminary evidence countering the unsubstantiated narrative that increased naloxone availability begets more high-risk opioid use and further supports increasing naloxone access.

Published
2021

10. Carbamazepine Induces Focused T Cell Responses in Resolved Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Cases But Does Not Perturb the Immunopeptidome for T Cell Recognition

Author

Mifsud, Nicole A., primary, Illing, Patricia T., additional, Lai, Jeffrey W., additional, Fettke, Heidi, additional, Hensen, Luca, additional, Huang, Ziyi, additional, Rossjohn, Jamie, additional, Vivian, Julian P., additional, Kwan, Patrick, additional, and Purcell, Anthony W., additional

Published
2021
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13. Hong Kong Anaphylaxis Consortium Consensus Statements on prescription of adrenaline autoinjectors in the acute care setting

Author

Li, Philip H., primary, Chua, Gilbert T., additional, Leung, Agnes S.Y., additional, Chan, Yiu-Cheung, additional, Chan, Karen K.L., additional, Cheung, Koon-Ho, additional, Chong, Patrick C.Y., additional, Ho, Polly P.K., additional, Kwan, Mike Y.W., additional, Lai, Jeffrey C.H., additional, Lam, Kin-Kwai, additional, Lam, Tommy S.K., additional, Leung, Ting-Fan, additional, Li, Tin-Yan, additional, Duque, Jaime S. Rosa, additional, So, Jerome L.T., additional, Wan, Kuang-An, additional, Wong, Henry C.Y., additional, Wu, Adrian Y.Y., additional, Lee, Tak-Hong, additional, Ho, Marco H.K., additional, and Siu, Axel Y.C., additional

Published
2021
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16. Hip fracture risk in relation to vitamin D supplementation and serum 25-hydroxyvitamin D levels: a systematic review and meta-analysis of randomised controlled trials and observational studies

Author

Roddam Andrew W, Clements Mark S, Lucas Robyn M, Lai Jeffrey K C, and Banks Emily

Subjects
Public aspects of medicine, RA1-1270
Abstract

Abstract Background Vitamin D supplementation for fracture prevention is widespread despite conflicting interpretation of relevant randomised controlled trial (RCT) evidence. This study summarises quantitatively the current evidence from RCTs and observational studies regarding vitamin D, parathyroid hormone (PTH) and hip fracture risk. Methods We undertook separate meta-analyses of RCTs examining vitamin D supplementation and hip fracture, and observational studies of serum vitamin D status (25-hydroxyvitamin D (25(OH)D) level), PTH and hip fracture. Results from RCTs were combined using the reported hazard ratios/relative risks (RR). Results from case-control studies were combined using the ratio of 25(OH)D and PTH measurements of hip fracture cases compared with controls. Original published studies of vitamin D, PTH and hip fracture were identified through PubMed and Web of Science databases, searches of reference lists and forward citations of key papers. Results The seven eligible RCTs identified showed no significant difference in hip fracture risk in those randomised to cholecalciferol or ergocalciferol supplementation versus placebo/control (RR = 1.13[95%CI 0.98-1.29]; 801 cases), with no significant difference between trials of 21 (heterogeneity) = 51.02, p < 0.001) and significant heterogeneity was present overall (χ216 (heterogeneity) = 137.9, p < 0.001). Serum PTH levels in hip fracture cases did not differ significantly from controls, based on ten case-control studies with 905 cases (χ29 (heterogeneity) = 149.68, p < 0.001). Conclusions Neither higher nor lower dose vitamin D supplementation prevented hip fracture. Randomised and observational data on vitamin D and hip fracture appear to differ. The reason for this is unclear; one possible explanation is uncontrolled confounding in observational studies. Post-fracture PTH levels are unrelated to hip fracture risk.

Published
2010
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18. An emergency department order set for buprenorphine-naloxone (SUBOXONE®) initiation.

Author

Babu, Kavita M., Lai, Jeffrey T., Cushman, Phoebe A., Monfreda, Anthony, Sanseverino, Alexandra M., Dinapoli, Michael, and Gonzalez, Gerardo

Subjects
*BUPRENORPHINE, *NALOXONE, *EMERGENCY medical services
Abstract

Emergency Department (ED)-based initiation of buprenorphine-naloxone is increasingly recognized as standard care in treating patients with opioid withdrawal and opioid use disorders. We provide an ED buprenorphine-naloxone order set to facilitate home and in-ED induction. This clinical tool was developed by an interdisciplinary group of experts at our institution. We were unable to identify any similar electronic decision-support tools for reference when we created our own. Our goal in sharing this order set is to accelerate the development of similar tools in other healthcare settings. [ABSTRACT FROM AUTHOR]

Published
2020
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20. Structures of the Neisseria meningitides methionine‐binding protein MetQ in substrate‐free form and bound to l‐ and d‐methionine isomers.

Author

Nguyen, Phong T., Lai, Jeffrey Y., Kaiser, Jens T., and Rees, Douglas C.

Abstract

The bacterial periplasmic methionine‐binding protein MetQ is involved in the import of methionine by the cognate MetNI methionine ATP binding cassette (ABC) transporter. The MetNIQ system is one of the few members of the ABC importer family that has been structurally characterized in multiple conformational states. Critical missing elements in the structural analysis of MetNIQ are the structure of the substrate‐free form of MetQ, and detailing how MetQ binds multiple methionine derivatives, including both l‐ and d‐methionine isomers. In this study, we report the structures of the Neisseria meningitides MetQ in substrate‐free form and in complexes with l‐methionine and with d‐methionine, along with the associated binding constants determined by isothermal titration calorimetry. Structures of the substrate‐free (N238A) and substrate‐bound N. meningitides MetQ are related by a "Venus‐fly trap" hinge‐type movement of the two domains accompanying methionine binding and dissociation. l‐ and d‐methionine bind to the same site on MetQ, and this study emphasizes the important role of asparagine 238 in ligand binding and affinity. A thermodynamic analysis demonstrates that ligand‐free MetQ associates with the ATP‐bound form of MetNI ∼40 times more tightly than does liganded MetQ, consistent with the necessity of dissociating methionine from MetQ for transport to occur. [ABSTRACT FROM AUTHOR]

Published
2019
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21. RNF43 germline and somatic mutation in serrated neoplasia pathway and its association with BRAF mutation

Author

Yan, Helen H N, Lai, Jeffrey C W, Ho, Siu Lun, Leung, Wai Keung, Law, Wai Lun, Lee, Janet F Y, Chan, Anthony K W, Tsui, Wai Yin, Chan, Annie S Y, Lee, Bernard C H, Yue, Sarah S K, Man, Alice H Y, Clevers, Hans, Yuen, Siu Tsan, Leung, Suet Yi, Yan, Helen H N, Lai, Jeffrey C W, Ho, Siu Lun, Leung, Wai Keung, Law, Wai Lun, Lee, Janet F Y, Chan, Anthony K W, Tsui, Wai Yin, Chan, Annie S Y, Lee, Bernard C H, Yue, Sarah S K, Man, Alice H Y, Clevers, Hans, Yuen, Siu Tsan, and Leung, Suet Yi

Abstract

OBJECTIVE: Serrated polyps (hyperplastic polyps, sessile or traditional serrated adenomas), which can arise in a sporadic or polyposis setting, predispose to colorectal cancer (CRC), especially those with microsatellite instability (MSI) due to MLH1 promoter methylation (MLH1(me+)). We investigate genetic alterations in the serrated polyposis pathway.DESIGN: We used a combination of exome sequencing and target gene Sanger sequencing to study serrated polyposis families, sporadic serrated polyps and CRCs, with validation by analysis of The Cancer Genome Atlas (TCGA) cohort, followed by organoid-based functional studies.RESULTS: In one out of four serrated polyposis families, we identified a germline RNF43 mutation that displayed autosomal dominant cosegregation with the serrated polyposis phenotype, along with second-hit inactivation through loss of heterozygosity or somatic mutations in all serrated polyps (16), adenomas (5) and cancer (1) examined, as well as coincidental BRAF mutation in 62.5% of the serrated polyps. Concurrently, somatic RNF43 mutations were identified in 34% of sporadic sessile/traditional serrated adenomas, but 0% of hyperplastic polyps (p=0.013). Lastly, in MSI CRCs, we found significantly more frequent RNF43 mutations in the MLH1(me+) (85%) versus MLH1(me-) (33.3%) group (p<0.001). These findings were validated in the TCGA MSI CRCs (p=0.005), which further delineated a significant differential involvement of three Wnt pathway genes between these two groups (RNF43 in MLH1(me+); APC and CTNNB1 in MLH1(me-)); and identified significant co-occurrence of BRAF and RNF43 mutations in the MSI (p<0.001), microsatellite stable (MSS) (p=0.002) and MLH1(me+) MSI CRCs (p=0.042). Functionally, organoid culture of serrated adenoma or mouse colon with CRISPR-induced RNF43 mutations had reduced dependency on R-spondin1.CONCLUSIONS: These results illustrate the importance of RNF43, along with BRAF mutation in the serrated neoplasi

Published
2016

22. 7th Drug hypersensitivity meeting: part two

Author

Elera, Javier Dionicio, primary, Boteanu, Cosmin, additional, Blanco, Maria Aranzazu Jimenez, additional, Gonzalez-Mendiola, Rosario, additional, García, Irene Carrasco, additional, Alvarez, Antonio, additional, Martinez, Jose Julio Laguna, additional, Garrido, Jaume Martí, additional, Barona, Carla Torán, additional, Chorda, Carolina Perales, additional, Salgueiro, Ramón López, additional, Palacios, Miguel Díaz, additional, De Rojas, Dolores Hernández Fernández, additional, Acar, Emre Ali, additional, Aktas, Ayse, additional, Ermertcan, Aylin Türel, additional, Temiz, Peyker, additional, Lin, Chien-Yio, additional, Hui, Chung-Yee Rosaline, additional, Chang, Ya-Ching, additional, Yang, Chih-Hsun, additional, Chung, Wen-Hung, additional, Carolino, Fabrícia, additional, Silva, Diana, additional, De Castro, Eunice Dias, additional, Cernadas, Josefina R., additional, Ensina, Luis Felipe, additional, Aranda, Carolina, additional, Nunes, Ines Camelo, additional, Lacerda, Alex, additional, Martins, Ana Maria, additional, Goudouris, Ekaterini, additional, Ribeiro, Marcia, additional, Da Silva Franco, José Francisco, additional, Queiroz, Leandra, additional, Solé, Dirceu, additional, Dalgiç, Ceyda Tunakan, additional, Sin, Aytül Zerrin, additional, Günsen, Fatma Düsünür, additional, Bulut, Gökten, additional, Ardeniz, Fatma Ömür, additional, Gülbahar, Okan, additional, Gökmen, Emine Nihal Mete, additional, Kokuludag, Ali, additional, De Francisco, Ana M. Montoro, additional, De Vicente Jiménez, Talía Mª, additional, Mendoza Parra, Adriana M., additional, Burgos Pimentel, Angella M., additional, Luque, Amelia García, additional, Amaral, Luis, additional, Leão, Leonor Carneiro, additional, Pinto, Nicole, additional, Belo, Joana, additional, Marques, João, additional, Carreiro-Martins, Pedro, additional, Leiria-Pinto, Paula, additional, Chaabane, Amel, additional, Romdhane, Haifa Ben, additional, Fredj, Nadia Ben, additional, Chadly, Zohra, additional, Boughattas, Naceur A., additional, Aouam, Karim, additional, Uyttebroek, Astrid P., additional, Bridts, Chris H., additional, Romano, Antonino, additional, Ebo, Didier G., additional, Sabato, Vito, additional, Lopes, Anabela, additional, Cosme, Joana, additional, Aguiar, Rita, additional, Lourenço, Tatiana, additional, Paes, Maria-João, additional, Spínola-Santos, Amélia, additional, Pereira-Barbosa, Manuel, additional, Cruz, Cíntia Rito, additional, Dos Reis, Rute Pereira, additional, Tomaz, Elza, additional, Pires, Ana Paula, additional, Inácio, Filipe, additional, Benito-Garcia, Filipe, additional, Mota, Inês, additional, Correia, Magna, additional, Gaspar, Ângela, additional, Chambel, Marta, additional, Piedade, Susana, additional, Morais-Almeida, Mário, additional, Nakonechna, Alla, additional, Antipkin, Yurij, additional, Umanets, Tetiana, additional, Pineda, Fernando, additional, Arribas, Francisca, additional, Lapshyn, Volodymyr, additional, Miranda, Pablo Andrés, additional, De La Cruz Hoyos, Bautista, additional, Blanco, Aranzazu Jimenez, additional, Del Pozo, Marta, additional, Vultaggio, Alessandra, additional, Nencini, Francesca, additional, Pratesi, Sara, additional, Matucci, Andrea, additional, Maggi, Enrico, additional, Cegec, Ivana, additional, Nahal, Danica Juricic, additional, Turk, Viktorija Erdeljic, additional, Aumiler, Matea Radacic, additional, Ausperger, Ksenija Makar, additional, Kraljickovic, Iva, additional, Simic, Iveta, additional, Yamaguchi, Yukie, additional, Watanabe, Tomoya, additional, Satoh, Megumi, additional, Tanegashima, Tomohiko, additional, Oda, Kayoko, additional, Wada, Hidefumi, additional, Aihara, Michiko, additional, Lee, Jaechun Jason, additional, Choi, Jay Chol, additional, Lee, Hwa Young, additional, Fernandes, Rosa-Anita Rodrigues, additional, Faria, Emília, additional, Pita, Joana, additional, Sousa, Nuno, additional, Ribeiro, Carmelita, additional, Carrapatoso, Isabel, additional, Bom, Ana Todo, additional, Rodolfo, Ana, additional, Dias-Castro, Eunice, additional, Voronova, Marina, additional, Valle, Diana Kury, additional, Coronel, Verónica Pacheco, additional, Chordá, Carolina Perales, additional, Madamba, Roselle Catherine Yu, additional, Ferrer, Marta, additional, Goikoetxea, Maria Jose, additional, D’Amelio, Carmen, additional, Bernad, Amalia, additional, Vega, Olga, additional, Gastaminza, Gabriel, additional, Bibián, Beatriz Pola, additional, Salazar, Marina Lluncor, additional, Vilà-Nadal, Gemma, additional, Roman, Ana María Fiandor, additional, Ortega, Javier Dominguez, additional, Muñoz, Miguel Gonzalez, additional, Gancedo, Santiago Quirce, additional, Moreno, Maria Rosario Cabañas, additional, Hofmeier, Kathrin Scherer, additional, Barzylovych, Vladyslava, additional, Pola, Beatriz, additional, Lluncor, Marina, additional, Fiandor, Ana, additional, Bellón, Teresa, additional, Domínguez, Javier, additional, Quirce, Santiago, additional, Yang, Min-Suk, additional, Kim, Sun-Sin, additional, Kim, Sae-Hoon, additional, Kang, Hye-Ryun, additional, Park, Heung-Woo, additional, Cho, Sang-Heon, additional, Min, Kyung-Up, additional, Chang, Yoon-Seok, additional, Delahaye, Clémence, additional, Flabbee, Jenny, additional, Waton, Julie, additional, Bauvin, Olivia, additional, Barbaud, Annick, additional, Fadhel, Najah Ben, additional, Gulin, Sandra Jerkovic, additional, Chiriac, Anca, additional, Cardoso, Bárbara Kong, additional, Viseu, Regina, additional, Moreira, Ana, additional, Cadinha, Susana, additional, Neves, Ana Castro, additional, Barreira, Patrícia, additional, Malheiro, Daniela, additional, Da Silva, J. P. Moreira, additional, Jurakic-Toncic, Ružica, additional, Ljubojevic, Suzana, additional, Turcic, Petra, additional, Gilissen, Liesbeth, additional, Huygens, Sara, additional, Goossens, An, additional, Andreu, Inmaculada, additional, Romero, Alicia Martinez, additional, Cabezas, Pau Gomez, additional, Parejo, Pedro Ayuso, additional, Del Carmen Plaza-Serón, Maria, additional, Doña, Inmaculada, additional, Blanca-López, Natalia, additional, Flores, Carlos, additional, Galindo, María Luisa, additional, Molina, Ana, additional, Perkins, James Richard, additional, Cornejo-García, José Antonio, additional, García-Agúndez, José Augusto, additional, García-Martín, Elena, additional, Campo, Paloma, additional, Canto, María Gabriela, additional, Blanca, Miguel, additional, Guéant-Rodríguez, Rosa María, additional, Jurado-Escobar, Raquel, additional, Barrionuevo, Esther, additional, Salas, María, additional, Canto, Gabriela, additional, Guéant, Jean-Louis, additional, Usui, Toru, additional, Tailor, Arun, additional, Faulkner, Lee, additional, Farrell, John, additional, Alfirevic, Ana, additional, Kevin Park, B., additional, Naisbitt, Dean J., additional, Trelles, Oswaldo, additional, Guerrero, María Auxiliadora, additional, Upton, Alex, additional, Ueta, Mayumi, additional, Sawai, Hiromi, additional, Sotozono, Chie, additional, Tokunaga, Katushi, additional, Kinoshita, Shigeru, additional, Sukasem, Chonlaphat, additional, Satapornpong, Patompong, additional, Tempark, Therdpong, additional, Rerknimitr, Pawinee, additional, Pairayayutakul, Kulprapat, additional, Klaewsongkram, Jettanong, additional, Koomdee, N., additional, Jantararoungtong, T., additional, Santon, S., additional, Puangpetch, A., additional, Intusoma, U., additional, Tassaneeyakul, W., additional, Theeramoke, V., additional, Ramirez, Elena, additional, Borobia, Alberto Manuel, additional, Tong, Hoi, additional, Castañer, Jose Luis, additional, De Abajo, Francisco José, additional, Galvao, Violeta Régnier, additional, Pavlos, Rebecca, additional, Mckinnon, Elizabeth, additional, Williams, Kristina, additional, Beeghly-Fadiel, Alicia, additional, Redwood, Alec, additional, Phillips, Elizabeth, additional, Castells, Mariana, additional, Boni, Elisa, additional, Russello, Marina, additional, Mauro, Marina, additional, Ue, Kok Loong, additional, Rutkowski, Krzysztof, additional, Gomis, Victor Soriano, additional, Ferre, Jorge Frances, additional, Rodriguez, Angel Esteban, additional, Reig, Vicente Cantó, additional, Sanchez, Javier Fernandez, additional, Breynaert, Christine, additional, Van Hoeyveld, Erna, additional, Schrijvers, Rik, additional, Irigoyen, Raquel Fuentes, additional, Collado, Daniel, additional, Vida, Yolanda, additional, Najera, Francisco, additional, Perez-Inestrosa, Ezequiel, additional, Mesa-Antunez, Pablo, additional, Mayorga, Cristobalina, additional, Torres, María José, additional, Tannert, Line K., additional, Mortz, Charlotte G., additional, Skov, Per Stahl, additional, Bindslev-Jensen, Carsten, additional, Pfützner, Wolfgang, additional, Dörnbach, Hannah, additional, Visse, Johanna, additional, Rauber, Michele, additional, Möbs, Christian, additional, Elzagallaai, Abdelbaset A., additional, Chow, Lindsey, additional, Abuzgaia, Awatif M., additional, Rieder, Michael J., additional, Trubiano, Jason, additional, Woolnough, Emily, additional, Stautins, Kaija, additional, Cheng, Christina, additional, Kato, Kenichi, additional, Azukizawa, Hiroaki, additional, Hanafusa, Takaaki, additional, Katayama, Ichiro, additional, Fujiyama, Toshiharu, additional, Hashizume, Hideo, additional, Umayahara, Takatsune, additional, Ito, Taisuke, additional, Tokura, Yoshiki, additional, Silar, Mira, additional, Zidarn, Mihaela, additional, Rupnik, Helena, additional, Korosec, Peter, additional, Redwood, Alec James, additional, Strautins, Kaija, additional, White, Katie, additional, Chopra, Abha, additional, Konvinse, Katherine, additional, Leary, Shay, additional, Mallal, Simon, additional, Cabañas, Rosario, additional, Fiandor, Ana María, additional, Sullivan, Andrew, additional, Whitaker, Paul, additional, Peckham, Daniel, additional, Haw, Wei Yann, additional, Polak, Marta E., additional, Mcguire, Carolann, additional, Ardern-Jones, Michael R., additional, Aoyama, Yumi, additional, Shiohara, Tetsuo, additional, Correia, Sara, additional, Gelincik, Asli, additional, Demir, Semra, additional, Sen, Fatma, additional, Bozbey, Hamza Ugur, additional, Olgac, Muge, additional, Unal, Derya, additional, Coskun, Raif, additional, Colakoglu, Bahauddin, additional, Buyuozturk, Suna, additional, Çatin-Aktas, Esin, additional, Deniz, Gunnur, additional, Laguna, Jose Julio, additional, Dionicio, J., additional, Fernandez, Tahia, additional, Olazabal, I., additional, Ruiz, Maria Dolores, additional, Torres, Maria José, additional, Lafuente, Alberto, additional, Núñez, Jorge, additional, Fernández, Tahia Diana, additional, Palomares, Francisca, additional, Fernández, Rubén, additional, Sanchez, Maria Isabel, additional, Fernandez, Tahía, additional, Ruiz, Arturo, additional, Ariza, Adriana, additional, Alonso, Amalia Bernad, additional, Garófalo, Carmen D’Amelio, additional, Matute, Olga Vega, additional, Puga, Marta Ferrer, additional, Lapresa, María José Goikoetxea, additional, Lasarte, Gabriel Gastaminza, additional, Thinnes, Antonia, additional, Merk, Hans F., additional, Baron, Jens Malte, additional, Leverkus, Martin, additional, Balakirski, Galina, additional, Gibson, Andrew, additional, Ogese, Monday, additional, Al-Attar, Zaid, additional, Yaseen, Fiazia, additional, Meng, Xiaoli, additional, Jenkins, Rozalind, additional, Farrel, John, additional, Alhilali, Khetam, additional, Xue, Yanni, additional, Illing, Patricia, additional, Mifsud, Nicole, additional, Fettke, Heidi, additional, Lai, Jeffrey, additional, Ho, Rebecca, additional, Kwan, Patrick, additional, Purcell, Anthony, additional, Ogese, Monday O., additional, Betts, Catherine, additional, Thomson, Paul, additional, Alhaidari, Mohammad, additional, Berry, Neill, additional, O’Neill, Paul M., additional, Alzahrani, Abdulaziz, additional, Azoury, Marie Eliane, additional, Fili, Lucia, additional, Bechara, Rami, additional, Scornet, Noémie, additional, Nhim, Cathy, additional, Weaver, Richard, additional, Claude, Nancy, additional, Joseph, Delphine, additional, Maillere, Bernard, additional, Parronchi, Paola, additional, Pallardy, Marc, additional, Villani, Axel Patrice, additional, Rozières, Aurore, additional, Bensaïd, Benoît, additional, Tardieu, Mathilde, additional, Albert, Floriane, additional, Mutez, Virginie, additional, Baysal, Tugba, additional, Maryanski, Janet, additional, Nicolas, Jean-François, additional, Kanagawa, Osami, additional, Vocanson, Marc, additional, Hung, Shuen-Iu, additional, Harrison, Caroline J., additional, Jenkins, Rosalind E., additional, French, Neil S., additional, Montañez, Maria Isabel, additional, Fernandez, Tahia D., additional, Martin-Serrano, Angela, additional, Torres, Maria Jose, additional, Molina, Noemi, additional, Wood, Sally, additional, Pirmohamed, Munir, additional, Montañez, María Isabel, additional, Martín-Serrano, Ángela, additional, Pérez-Inestrosa, Ezequiel, additional, Pérez-Sala, Dolores, additional, Guzmán, Antonio E., additional, Ko, Tai-Ming, additional, Chen, Yuan-Tsong, additional, Wu, Jer-Yuarn, additional, Sánchez-Gómez, Francisco J., additional, González-Morena, Juan M., additional, Torres, María J., additional, Arreola, Alejandra Monroy, additional, Corona, Jesus Agustin Badillo, additional, Flores, Silvia Mendez, additional, Cherit, Judith Dominguez, additional, Figueroa, Noe Valentin Duran, additional, Flores, Jose Luis Castrejon, additional, Perkins, James, additional, Pérez-Alzate, Diana, additional, Bogas, Gador, additional, Torres, María J, additional, Marti, Luis Mario Tubella, additional, De La Losa, Fernando Pineda, additional, Poves, Francisca Arribas, additional, Lopez, Jaime Tubella, additional, and Santiago, Teodora Lopez, additional

Published
2016
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24. Prospective observational study of physical functioning, physical activity and time outdoors and the risk of hip fracture: A population-based cohort study of 158,057 older adults in the 45 and Up Study

Author

Lai, Jeffrey, Armstrong, Miranda E, Banks, Emily, Lucas, Robyn, Lai, Jeffrey, Armstrong, Miranda E, Banks, Emily, and Lucas, Robyn

Abstract

Low levels of physical activity or sun exposure and limitations to physical functioning (or disability) have been identified as possible risk factors for hip fracture. However, these factors are closely related, and data on their independent and joint ass

Published
2013

25. Variability in vitamin D assays impairs clinical assessment of vitamin D status

Author

Lai, Jeffrey, Ponsonby, Anne-Louise, Banks, Emily, Ausimmune Investigator Group (AIG), Lucas, Robyn, Lai, Jeffrey, Ponsonby, Anne-Louise, Banks, Emily, Ausimmune Investigator Group (AIG), and Lucas, Robyn

Abstract

Background: Measuring serum 25(OH)D concentration is common in clinical practice despite the questionable reliability of assays. Aims: The aim of the present study was to examine agreement in 25(OH)D concentrations measured by different assays and laboratories, and consider related clinical implications. Methods: Serum samples from 813 participants in the Australian Multicentre Study of Environment and Immune Function (the Ausimmune Study) were assayed for 25(OH)D concentration. Duplicate samples from subsets of subjects were sent to different laboratories, two using DiaSorin Liaison (Laboratory A and B) and one using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS - selected here as the nominal gold standard). Pairwise within-assay (both within-laboratory and between-laboratories) and between-assay agreement was examined using Deming regression and Bland-Altman plots. Common 25(OH)D cut-points for classification of vitamin D deficiency were used to compare the different assays. Results: 25(OH)D concentrations measured using Liaison were substantially lower at Laboratory A than at Laboratory B (mean bias -11.60nmol/L, 95% limits of agreement -46.39, 23.18). Both Liaison assays returned much lower 25(OH)D concentrations than LC-MS/MS (mean bias up to -26.05nmol/L, 95% limits of agreement of -13.21, 65.31). For Laboratory A participants, 46% (355/765) were classified as vitamin D deficient (25(OH)D <50nmol/L) using Liaison compared with 17% (128/765) using LC-MS/MS. For Laboratory B participants, the respective figures were 36% (76/209) and 20% (41/209). Hence, between 1-in-5 and 1-in-3 participants were misclassified as 'deficient'. Conclusion: Bias and variability in 25(OH)D measurements sufficient to affect significantly clinical decision-making were found both between-laboratories and between-assays. The adoption of common standards to allow assay calibration is required urgently.

Published
2012

26. Assessing vitamin D status: Pitfalls for the unwary

Author

Lai, Jeffrey, Clements, Mark, Harrison, Simone, Banks, Emily, Lucas, Robyn, Lai, Jeffrey, Clements, Mark, Harrison, Simone, Banks, Emily, and Lucas, Robyn

Abstract

The use of vitamin D testing has grown rapidly in the recent times as a result of increased interest in the role of vitamin D in health. Although the generally accepted measure of vitamin D status is circulating 25(OH)D concentration, there is little consensus on which assay method should be used. Commonly used assays include competitive proteinbinding assay, RIA, enzyme immunoassay, chemiluminescence immunoassays, HPLC, and LC-MS/MS, each with its own advantages and disadvantages. However, there is significant interassay and interlaboratory variability in measurements. Our simulation of the published data showed that using a deficiency cut-point of 50 nmol/L, 57% of samples assessed using a chemiluminescence immunoassay were classified as deficient compared with 41% of samples assessed using LC-MS/MS; a 20% misclassification rate. Similar rates of misclassification were seen at 75 nmol/L. This has implications for clinical practice and decision limits for vitamin D supplementation, suggesting that cut-points should be assay specific rather than universal and that greater harmonization between laboratories is required. Newer assays using alternative biological samples to determine the circulating 25(OH)D have been proposed and advances in the genetics of vitamin D and the role of vitamin D-binding protein may improve future assay accuracy.

Published
2010

28. Self-assembled lipid and membrane protein polyhedral nanoparticles

Author

Basta, Tamara, primary, Wu, Hsin-Jui, additional, Morphew, Mary K., additional, Lee, Jonas, additional, Ghosh, Nilanjan, additional, Lai, Jeffrey, additional, Heumann, John M., additional, Wang, Keeshia, additional, Lee, Y. C., additional, Rees, Douglas C., additional, and Stowell, Michael H. B., additional

Published
2013
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30. Factors Associated with Short-Term Hospital Readmission Rates for Breast Cancer Patients in Western Ausstralia: An Observational Study

Author

Lai, Jeffrey, Martin, Michael, Meyricke, Ramona, O'Neill, Terence, Roberts, Steven, Lai, Jeffrey, Martin, Michael, Meyricke, Ramona, O'Neill, Terence, and Roberts, Steven

Abstract

Background: Unplanned hospital readmissions after surgical treatment for breast cancer are an indicator of morbidity. We explore the relationship between the rate of unplanned hospital readmissions within 42 days of initial treatment and various factors

Published
2007

33. An optimal data mining algorithm

Author

Lai, Jeffrey Siu Sun and Lai, Jeffrey Siu Sun

Abstract

Knowledge discovery or data mining is the search for relationships and global patterns that exist in large databases. One of the main problems for knowledge discovery is that the number of possible relationships is very large, thus prohibiting the search for the correct ones by simply validating each of them. Special logic/intelligence has to be used in the discovery strategies such that the target relationships can be found effectively. In this thesis, a general rule discovery algorithm, DA-2, is proposed to discover non-recursive Datalog rules from a set of background information with the input of a set of training data or examples. Most other discovery algorithms use greedy approaches to find the target knowledge. In a greedy approach, the system cannot guarantee the quality of the found rule(s). DA-2 uses a best first search type of logic together with a 'goodness' measure to determine the target knowledge. Unlike algorithms that use greedy approaches, DA-2 can guarantee that the rules found are the 'best' amongst the solution space within given constraints and without exhaustive search.

Published
1996

34. An Engineered Zinc Finger Protein Activator of the Endogenous Glial Cell Line-Derived Neurotrophic Factor Gene Provides Functional Neuroprotection in a Rat Model of Parkinson's Disease.

Author

Laganiere, Josee, Keils, Adrian P., Lai, Jeffrey T., Guschin, Dmitry, Paschon, David E., Xiangdong Meng, Fong, Lauren K., Qi Yu, Rebar, Edward J., Gregory, Philip D., Bankiewicz, Krystof S., Forsayeth, John, and Zhang, H. Steve

Subjects
DOPAMINERGIC neurons, PARKINSON'S disease, TRANSCRIPTION factors, CELL lines, AMPHETAMINES
Abstract

Loss of dopaminergic neurons is primarily responsible for the onset and progression of Parkinson's disease (PD); thus, neuroprotective and/or neuroregenerative strategies remain critical to the treatment of this increasingly prevalent disease. Here we explore a novel approach to neurotrophic factor-based therapy by engineering zinc finger protein transcription factors (ZFP IFs) that activate the expression of the endogenous glial cell line-derived neurotrophic factor (GDNF) gene. We show that GDNF activation can be achieved with exquisite genome-wide specificity. Furthermore, in a rat model of PD, striatal delivery of an adeno-associated viral vector serotype 2 encoding the GDNF activator resulted in improvements in forelimb akinesia, sensorimotor neglect, and amphetamine-induced rotations caused by 6-hydroxydopamine (6-OHDA) lesion. Our results suggest that an engineered ZFP IF can drive sufficient GDNF expression in the brain to provide functional neuroprotection against 6-OHDA; therefore, targeted activation of the endogenous gene may provide a method for delivering appropriate levels of GDNF to PD patients. [ABSTRACT FROM AUTHOR]

Published
2010
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35. Structures of the Neisseria meningitides methionine-binding protein MetQ in substrate-free form and bound to l- and d-methionine isomers.

Author

Nguyen PT, Lai JY, Kaiser JT, and Rees DC

Subjects
Binding Sites, Models, Molecular, Molecular Structure, Stereoisomerism, Bacterial Proteins chemistry, Methionine chemistry, Neisseria meningitidis chemistry
Abstract

The bacterial periplasmic methionine-binding protein MetQ is involved in the import of methionine by the cognate MetNI methionine ATP binding cassette (ABC) transporter. The MetNIQ system is one of the few members of the ABC importer family that has been structurally characterized in multiple conformational states. Critical missing elements in the structural analysis of MetNIQ are the structure of the substrate-free form of MetQ, and detailing how MetQ binds multiple methionine derivatives, including both l- and d-methionine isomers. In this study, we report the structures of the Neisseria meningitides MetQ in substrate-free form and in complexes with l-methionine and with d-methionine, along with the associated binding constants determined by isothermal titration calorimetry. Structures of the substrate-free (N238A) and substrate-bound N. meningitides MetQ are related by a "Venus-fly trap" hinge-type movement of the two domains accompanying methionine binding and dissociation. l- and d-methionine bind to the same site on MetQ, and this study emphasizes the important role of asparagine 238 in ligand binding and affinity. A thermodynamic analysis demonstrates that ligand-free MetQ associates with the ATP-bound form of MetNI ∼40 times more tightly than does liganded MetQ, consistent with the necessity of dissociating methionine from MetQ for transport to occur., (© 2019 The Authors. Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.)

Published
2019
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