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1. Trend in Clinical Trial Participation During COVID-19: A Secondary Analysis of the I-SPY COVID Clinical Trial

Author

Philip Yang, MD, MSc, Neal W. Dickert, MD, PhD, Angela Haczku, MD, PhD, Christine Spainhour, RN, CCRC, Sara C. Auld, MD, MSc, the I-SPY COVID Consortium, Neil R. Aggarwal, MD, MHSc, Timothy Albertson, MD, Sara Auld, MD, Jeremy R. Beitler, MD, MPH, Paul Berger, DO, Ellen L. Burnham, MD, Carolyn S. Calfee, MD, MAS, Nathan Cobb, MD, Alessio Crippa, PhD, Andrea Discacciati, PhD, Martin Eklund, PhD, Laura Esserman, MD, MBA, D. Clark Files, MD, Eliot Friedman, MD, Sheetal Gandotra, MD, Kashif Khan, MD, Jonathan Koff, MD, Santhi Kumar, MD, Kathleen D. Liu, MD, PhD, Thomas R. Martin, MD, Michael A. Matthay, MD, Nuala J. Meyer, MD, Timothy Obermiller, MD, MS, Philip Robinson, MD, Derek Russell, MD, Karl Thomas, MD, Se Fum Wong, MD, Richard G. Wunderink, MD, Mark M. Wurfel, PhD, MD, Albert Yen, MD, Fady A. Youssef, MD, Anita Darmanian, MD, Amy L. Dzierba, PharmD, Ivan Garcia, RRT, Katarzyna Gosek, PharmD, Purnema Madahar, MD, MS, Aaron M. Mittel, MD, Justin Muir, PharmD, Amanda Roden, MD, John Schicchi, MD, Alexis L. Serra, MD, MPH, Romina Wahab, MD, Kevin W. Gibbs, MD, Leigha Landreth, RN, Mary LaRose, RN, Lisa Parks, RN, Adina Wynn, MPH, CCRP, Caroline A. G. Ittner, PhD, Nilam S. Mangalmurti, MD, John P. Reilly, MD, MS, Donna Harris, BSN, Abhishek Methukupally, MBBS, Siddharth Patel, MBBS, MPH, Lindsie Boerger, BA, John Kazianis, MD, Carrie Higgins, Jeff McKeehan, MS, Brian Daniel, RCP, RRT, Scott Fields, PharmD, James Hurst-Hopf, MS, Alejandra Jauregui, BA, Lamorna Brown Swigart, PhD, Daniel Belvins, CCRP, Catherine Nguyen, MD, Alexis Suarez, MS, Maged A. Tanios, MD, Farjad Sarafian, MD, Usman Shah, MD, Max Adelman, MD, MSc, Christina Creel-Bulos, MD, Joshua Detelich, MD, Gavin Harris, MD, Katherine Nugent, MD, Philip Yang, MD, Erin Hardy, Richart Harper, MD, Brian Morrissey, MD, Christian Sandrock, MD, MPH, G. R. Scott Budinger, MD, Helen K. Donnelly, RN, BSN, Benjamin D. Singer, MD, Ari Moskowitz, MD, Melissa Coleman, MD, Joseph Levitt, MD, Ruixiao Lu, PhD, Paul Henderson, PhD, Adam Asare, PhD, Imogene Dunn, PhD, and Alejandro Botello Barragan

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

OBJECTIVES:. To analyze the temporal trend in enrollment rates in a COVID-19 platform trial during the first three waves of the pandemic in the United States. DESIGN:. Secondary analysis of data from the I-SPY COVID randomized controlled trial (RCT). SETTING:. Thirty-one hospitals throughout the United States. PATIENTS:. Patients who were approached, either directly or via a legally authorized representative, for consent and enrollment into the I-SPY COVID RCT. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Among 1,338 patients approached for the I-SPY COVID trial from July 30, 2020, to February 17, 2022, the number of patients who enrolled (n = 1,063) versus declined participation (n = 275) was used to calculate monthly enrollment rates. Overall, demographic and baseline clinical characteristics were similar between those who enrolled versus declined. Enrollment rates fluctuated over the course of the COVID-19 pandemic, but there were no significant trends over time (Mann-Kendall test, p = 0.21). Enrollment rates were also comparable between vaccinated and unvaccinated patients. In multivariable logistic regression analysis, age, sex, region of residence, COVID-19 severity of illness, and vaccination status were not significantly associated with the decision to decline consent. CONCLUSIONS:. In this secondary analysis of the I-SPY COVID clinical trial, there was no significant association between the enrollment rate and time period or vaccination status among all eligible patients approached for clinical trial participation. Additional studies are needed to better understand whether the COVID-19 pandemic has altered clinical trial participation and to develop strategies for encouraging participation in future COVID-19 and critical care clinical trials.

Published
2023
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2. Report of the first seven agents in the I-SPY COVID trial: a phase 2, open label, adaptive platform randomised controlled trialResearch in context

Author

D. Clark Files, Neil Aggarwal, Timothy Albertson, Sara Auld, Jeremy R. Beitler, Paul Berger, Ellen L. Burnham, Carolyn S. Calfee, Nathan Cobb, Alessio Crippa, Andrea Discacciati, Martin Eklund, Laura Esserman, Eliot Friedman, Sheetal Gandotra, Kashif Khan, Jonathan Koff, Santhi Kumar, Kathleen D. Liu, Thomas R. Martin, Michael A. Matthay, Nuala J. Meyer, Timothy Obermiller, Philip Robinson, Derek Russell, Karl Thomas, Se Fum Wong, Richard G. Wunderink, Mark M. Wurfel, Albert Yen, Fady A. Youssef, Anita Darmanian, Amy L. Dzierba, Ivan Garcia, Katarzyna Gosek, Purnema Madahar, Aaron M. Mittel, Justin Muir, Amanda Rosen, John Schicchi, Alexis L. Serra, Romina Wahab, Kevin W. Gibbs, Leigha Landreth, Mary LaRose, Lisa Parks, Adina Wynn, Caroline A.G. Ittner, Nilman S. Mangalmurti, John P. Reilly, Donna Harris, Abhishek Methukupally, Siddharth Patel, Lindsie Boerger, John Kazianis, Carrie Higgins, Jeff McKeehan, Brian Daniel, Scott Fields, James Hurst-Hopf, Alejandra Jauregui, Lamorna Brown Swigart, Daniel Blevins, Catherine Nguyen, Alexis Suarez, Maged A. Tanios, Farjad Sarafian, Usman Shah, Max Adelman, Christina Creel-Bulos, Joshua Detelich, Gavin Harris, Katherine Nugent, Christina Spainhour, Philip Yang, Angela Haczku, Erin Hardy, Richart Harper, Brian Morrissey, Christian Sandrock, G. R. Scott Budinger, Helen K. Donnelly, Benjamin D. Singer, Ari Moskowitz, Melissa Coleman, Joseph Levitt, Ruixiao Lu, Paul Henderson, Adam Asare, Imogene Dunn, and Alejandro Botello Barragan

Subjects
SARS-CoV-2, Respiratory insufficiency, Clinical trial, Acute lung injury, Medicine (General), R5-920
Abstract

Summary: Background: An urgent need exists to rapidly screen potential therapeutics for severe COVID-19 or other emerging pathogens associated with high morbidity and mortality. Methods: Using an adaptive platform design created to rapidly evaluate investigational agents, hospitalised patients with severe COVID-19 requiring ≥6 L/min oxygen were randomised to either a backbone regimen of dexamethasone and remdesivir alone (controls) or backbone plus one open-label investigational agent. Patients were enrolled to the arms described between July 30, 2020 and June 11, 2021 in 20 medical centres in the United States. The platform contained up to four potentially available investigational agents and controls available for randomisation during a single time-period. The two primary endpoints were time-to-recovery (

Published
2023
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3. Multiplexed measurement of candidate blood protein biomarkers of heart failure

Author

Claire Tonry, Ken McDonald, Mark Ledwidge, Belinda Hernandez, Nadezhda Glezeva, Cathy Rooney, Brian Morrissey, Stephen R. Pennington, John A. Baugh, and Chris J. Watson

Subjects
Heart failure, Biomarkers, Proteomics, MRM, BNP, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Aims There is a critical need for better biomarkers so that heart failure can be diagnosed at an earlier stage and with greater accuracy. The purpose of this study was to design a robust mass spectrometry (MS)‐based assay for the simultaneous measurement of a panel of 35 candidate protein biomarkers of heart failure, in blood. The overall aim was to evaluate the potential clinical utility of this biomarker panel for prediction of heart failure in a cohort of 500 patients. Methods and results Multiple reaction monitoring (MRM) MS assays were designed with Skyline and Spectrum Mill PeptideSelector software and developed using nanoflow reverse phase C18 chromatographic Chip Cube‐based separation, coupled to a 6460 triple quadrupole mass spectrometer. Optimized MRM assays were applied, in a sample‐blinded manner, to serum samples from a cohort of 500 patients with heart failure and non‐heart failure (non‐HF) controls who had cardiovascular risk factors. Both heart failure with reduced ejection fraction (HFrEF) patients and heart failure with preserved ejection fraction (HFpEF) patients were included in the study. Peptides for the Apolipoprotein AI (APOA1) protein were the most significantly differentially expressed between non‐HF and heart failure patients (P = 0.013 and P = 0.046). Four proteins were significantly differentially expressed between non‐HF and the specific subtypes of HF (HFrEF and HFpEF); Leucine‐rich‐alpha‐2‐glycoprotein (LRG1, P

Published
2021
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4. A Randomized Clinical Trial of Antimicrobial Duration for Cystic Fibrosis Pulmonary Exacerbation Treatment

Author

Christopher H. Goss, Sonya L. Heltshe, Natalie E. West, Michelle Skalland, Don B. Sanders, Raksha Jain, Tara L. Barto, Barbra Fogarty, Bruce C. Marshall, Donald R. VanDevanter, Patrick A. Flume, Gregory Omlor, Brenda Bourne, Dion Roberts, Vicki Roberts, Samya Nasr, Dawn Kruse, Rachel Linnemann, Tsion Hailemichael, Caralee Forseen, Heidi Stapp, Natalie West, S. Patel, A. Claudio, Jerimiah Lysinger, Amy Harmala, George Solomon, Latona Kersh, Karen Miller, Dixie Durham, Ahmet Uluer, Robert Fowler, Carla Frederick, Nadine Caci, Charlotte Teneback, Julie Sweet, Michael Parkins, Clare Smith, Jennifer Goralski, Kelsey Haywood, Patrick Flume, Caroline Brailsford, Dana Albon, Christie Aderholt, Kimberly McBennett, Cindy Schaefer, Alpa Patel, April Hunt, Lauren Schumacher, Hari Polenakovik, Linda Clark, Jerry Nick, Katie Poch, Dana Kissner, James Cahill, Jorge Lascano, Erin Silverman, John McArdle, Alison Champagne, Robert Vender, Lisa Allwein, Lance Cohen, Norma (Jean) Barton, Tara Barto, Ami Patel, Cynthia Brown, Nia Vorhees, Michael Crosser, Lawrence Scott, Alix Ashare, Barbara Rodgers, Robert Zanni, Lisa Koval, Andrew Braun, Sophia Chiron Stevens, Maria Tupayachi Ortiz, Patricia Graham, Julie Biller, Erin Hubertz, Kathryn Moffett, Tammy Clark, Rebecca Griffith, Nancy Martinez, Sabiha Hussain, Fei Chen, Marie Egan, Catalina Guzman, Janice Wang, Aileen Espinal, Patricia Walker, Anne Kukral, Emily DiMango, Sarah Fracasso Francis, Carlos Milla, Colleen Dunn, Subramanyam Chittivelu, Ashley Scott, Daniel Dorgan, Sharon Ng, Joseph Pilewski, Rose Lanzo, Nauman Chaudary, Ryan Hayden, Steven Scofield, Barb Johnson, Brian Morrissey, Brandt Robinson, Douglas Conrad, Jenna Mielke, Moira Aitken, Chami Sanlors, Ravi Nayak, Freda Branch, Daniel Rosenbluth, Molly Siegel, Anil Ghimire, Mary Forell, Cori Daines, Monica Varela, Leslie Couch, Rebekah Hibbard, Allen Dozor, Armando Ramirez, Victor Ortega, Kathryn Kennedy, David Fish, and Karen Longtine

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Time Factors, Cystic Fibrosis, Exacerbation, Critical Care and Intensive Care Medicine, Cystic fibrosis, law.invention, Randomized controlled trial, law, Internal medicine, medicine, Humans, Pseudomonas Infections, Respiratory system, Respiratory Tract Infections, business.industry, Cystic Fibrosis Pulmonary Exacerbation, Editorials, Respiratory infection, Original Articles, Middle Aged, medicine.disease, Antimicrobial, Anti-Bacterial Agents, Respiratory Function Tests, Clinical trial, Pseudomonas aeruginosa, Disease Progression, Female, business
Abstract

RATIONALE: People with cystic fibrosis (CF) experience acute worsening of respiratory symptoms and lung function known as pulmonary exacerbations. Treatment with intravenous antimicrobials is common; however, there is scant evidence to support a standard treatment duration. OBJECTIVES: To test differing durations of intravenous antimicrobials for CF exacerbations. METHODS: STOP2 (Standardized Treatment of Pulmonary Exacerbations 2) was a multicenter, randomized, controlled clinical trial in exacerbations among adults with CF. After 7–10 days of treatment, participants exhibiting predefined lung function and symptom improvements were randomized to 10 or 14 days’ total antimicrobial duration; all others were randomized to 14 or 21 days’ duration. MEASUREMENTS AND MAIN RESULTS: The primary outcome was percent predicted FEV(1) (ppFEV(1)) change from treatment initiation to 2 weeks after cessation. Among early responders, noninferiority of 10 days to 14 days was tested; superiority of 21 days compared with 14 days was compared for the others. Symptoms, weight, and adverse events were secondary. Among 982 randomized people, 277 met improvement criteria and were randomized to 10 or 14 days of treatment; the remaining 705 received 21 or 14 days of treatment. Mean ppFEV(1) change was 12.8 and 13.4 for 10 and 14 days, respectively, a ‒0.65 difference (95% CI [‒3.3 to 2.0]), excluding the predefined noninferiority margin. The 21- and 14-day arms experienced 3.3 and 3.4 mean ppFEV(1) changes, a difference of ‒0.10 (‒1.3 to 1.1). Secondary endpoints and sensitivity analyses were supportive. CONCLUSIONS: Among adults with CF with early treatment improvement during exacerbation, ppFEV(1) after 10 days of intravenous antimicrobials is not inferior to 14 days. For those with less improvement after one week, 21 days is not superior to 14 days. Clinical trial registered with www.clinicaltrials.gov (NCT02781610).

Published
2021

5. Multiplexed measurement of candidate blood protein biomarkers of heart failure

Author

Chris Watson, Stephen R. Pennington, Nadezhda Glezeva, Brian Morrissey, Mark Ledwidge, John A. Baugh, Belinda Hernández, Cathy Rooney, Kenneth McDonald, and Claire Tonry

Subjects
Proteomics, medicine.medical_specialty, Heart failure, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Original Research Articles, Internal medicine, Natriuretic Peptide, Brain, medicine, Humans, Diseases of the circulatory (Cardiovascular) system, Original Research Article, 030212 general & internal medicine, Ejection fraction, business.industry, Area under the curve, Stroke Volume, Blood Proteins, Odds ratio, medicine.disease, Confidence interval, RC666-701, Cohort, Cardiology, Biomarker (medicine), MRM, Cardiology and Cardiovascular Medicine, Heart failure with preserved ejection fraction, business, Biomarkers, BNP
Abstract

AIMS: There is a critical need for better biomarkers so that heart failure can be diagnosed at an earlier stage and with greater accuracy. The purpose of this study was to design a robust mass spectrometry (MS)-based assay for the simultaneous measurement of a panel of 35 candidate protein biomarkers of heart failure, in blood. The overall aim was to evaluate the potential clinical utility of this biomarker panel for prediction of heart failure in a cohort of 500 patients.METHODS AND RESULTS: Multiple reaction monitoring (MRM) MS assays were designed with Skyline and Spectrum Mill PeptideSelector software and developed using nanoflow reverse phase C18 chromatographic Chip Cube-based separation, coupled to a 6460 triple quadrupole mass spectrometer. Optimized MRM assays were applied, in a sample-blinded manner, to serum samples from a cohort of 500 patients with heart failure and non-heart failure (non-HF) controls who had cardiovascular risk factors. Both heart failure with reduced ejection fraction (HFrEF) patients and heart failure with preserved ejection fraction (HFpEF) patients were included in the study. Peptides for the Apolipoprotein AI (APOA1) protein were the most significantly differentially expressed between non-HF and heart failure patients (P = 0.013 and P = 0.046). Four proteins were significantly differentially expressed between non-HF and the specific subtypes of HF (HFrEF and HFpEF); Leucine-rich-alpha-2-glycoprotein (LRG1, P < 0.001), zinc-alpha-2-glycoprotein (P = 0.005), serum paraoxanse/arylesterase (P = 0.013), and APOA1 (P = 0.038). A statistical model found that combined measurements of the candidate biomarkers in addition to BNP were capable of correctly predicting heart failure with 83.17% accuracy and an area under the curve (AUC) of 0.90. This was a notable improvement on predictive capacity of BNP measurements alone, which achieved 77.1% accuracy and an AUC of 0.86 (P = 0.005). The protein peptides for LRG1, which contributed most significantly to model performance, were significantly associated with future new onset HF in the non-HF cohort [Peptide 1: odds ratio (OR) 2.345 95% confidence interval (CI) (1.456-3.775) P = 0.000; peptide 2: OR 2.264 95% CI (1.422-3.605), P = 0.001].CONCLUSIONS: This study has highlighted a number of promising candidate biomarkers for (i) diagnosis of heart failure and subtypes of heart failure and (ii) prediction of future new onset heart failure in patients with cardiovascular risk factors. Furthermore, this study demonstrates that multiplexed measurement of a combined biomarker signature that includes BNP is a more accurate predictor of heart failure than BNP alone.

Published
2021

6. Worldwide Disparities in Recovery of Cardiac Testing 1 Year Into COVID-19

Author

Andrew J. Einstein, Cole Hirschfeld, Michelle C. Williams, Joao V. Vitola, Nathan Better, Todd C. Villines, Rodrigo Cerci, Leslee J. Shaw, Andrew D. Choi, Sharmila Dorbala, Ganesan Karthikeyan, Bin Lu, Valentin Sinitsyn, Alexey A. Ansheles, Takashi Kudo, Chiara Bucciarelli-Ducci, Bjarne Linde Nørgaard, Pál Maurovich-Horvat, Roxana Campisi, Elisa Milan, Lizette Louw, Adel H. Allam, Mona Bhatia, Lorenzo Sewanan, Eli Malkovskiy, Yosef Cohen, Michael Randazzo, Jagat Narula, Olga Morozova, Thomas N.B. Pascual, Yaroslav Pynda, Maurizio Dondi, Diana Paez, Gerd Hinterleitner, Yao Lu, Zhuoran Xu, Cole B. Hirschfeld, Ikenna Erinne, Mrinali Shetty, Andrew Choi, Juan Lopez-Mattei, Purvi Parwani, Artan Goda, Ervina Shirka, Salah Bouyoucef, Lydia Chelghoum, Farouk Mansouri, Abdelkader Medjahedi, Qais Naili, Mokhtar Ridouh, Diego Alasia, Lucia Alberghina, Natalia Aramayo, Diego Buchara, Franco Gabriel Busso, Jose Javier Bustos Rivadero, Jorge Camilletti, Hugo Campanelli, Ricardo Belisario Castro, Mariana Daicz, Horacio del Riego, Laura Dragonetti, Diego Echazarreta, Juan Erriest, Fernando Faccio, Adolfo Facello, Hugo Gallegos, Ricardo Geronazzo, Horacio Glait, Victor Hasbani, Victor Jäger, Julio Manuel Lewkowicz, Jose Lotti, Neiva Maciel, Osvaldo Masoli, Edgardo Mastrovito, Maria Medus, Maria Fernanda Merani, Susana Molteni, Marcos Montecinos, Gustavo Parisi, Claudio Pereyra Sueldo, Diego Perez de Arenaza, Luis Quintana, Alejandro Radzinschi, Marcela Redruello, Marina Rodríguez, Horacio Rojas, Arturo Romero Acuña, Daniel Schere, Sonia Traverso, Gustavo Vazquez, Susana Zeffiro, Mari Sakanyan, Scott Beuzeville, Raef Boktor, Michael Crowley, D'Arne Downie, Girish Dwivedi, Barry Elison, Omar Farouque, Kim Jasper, Subodh Joshi, Joseph Lee, Kenneth Lee, Elaine Lui, Peter Mcconachie, Joanne Meaker, Dee Nandurkar, Johanne Neill, Edward O'Rourke, Patricia O'Sullivan, George Pandos, Manuja Premaratne, David Prior, Natalie Rutherford, Connor Saunders, Kim Taubman, Andrew Tauro, Andrew Taylor, James Theuerle, Paul Thomas, Jonathan Tow, Anthony Upton, Shankar Vamadevan, Victor Wayne, Eva Alina Wegner, David Wong, John Younger, Dietrich Beitzke, Gudrun Feuchtner, Oliver Sommer, Konrad Weiss, Natallia Maroz-Vadalazhskaya, Uladzimir Tserakhau, Filip Homans, Caroline M. Van De Heyning, Raúl Araujo, Valentina Soldat-Stankovic, Sinisa Stankovic, Augusto Almeida, Carlos Anselmi, Guilherme S.A. Azevedo, Marcio Sommer Bittencourt, Diego Bromfman Pianta, Estevan Cabeda, Lara Carreira, Igor Coelho, Fernando de Amorim Fernandes, Andrea de Lorenzo, Roberta Delgado, Fernanda Erthal, Fabio Fernandes, Juliano Fernandes, Thiago Ferreira de Souza, Murilo Foppa, Wilson Furlan Matos Alves, Cibele Gontijo, Ilan Gottlieb, Gabriel Grossman, Maria Helena Albernaz Siqueira, Cesar Higa Nomura, Katia Hiromoto Koga, Ronaldo Lima, Rafael Lopes, Hugo Humberto Marçal Filho, Paulo Masiero, Luiz Mastrocola, Maria Eduarda Menezes de Siqueira, Claudio Mesquita, Danilo Naves, Filipe Penna, Ibraim Pinto, Thércio Rocha, Juliana Leal Rocha, Alfredo Rodrigues, Leila Salioni, Adelina Sanches, Marcelo Santos, Leonardo Sara Da Silva, Paulo Schvartzman, Cristina Sebastião Matushita, Tiago Senra, Marcelo Silva, Carlos Eduardo Soares, Bernardo Spiro, Carlos Eduardo Suaide Silva, Rafael Torres, Guilherme Urpia Monte, Andrea Vilela, Alexandre Volney Villa, Joao Vitola, Themissa Voss, Roberto Waltrick, Marcello Zapparoli, Hamid Naseer, Marina Garcheva-Tsacheva, Tiémégna Florence Ouattara, Sarameth Thou, Soley Varoeun, Gad Abikhzer, Rob Beanlands, Michael Chetrit, Dominique Dabreo, Carole Dennie, Matthias Friedrich, Mohmmed Nassoh Hafez, Kate Hanneman, Robert Miller, Anastasia Oikonomou, Idan Roifman, Gary Small, Vikas Tandon, Adwait Trivedi, James White, Katherine Zukotynski, Rita Alay, Carmen Concha, Teresa Massardo, Pedro Abad, Kelly Anzola, Harold Arturo, Luis Benitez, Alberto Cadena, Carlos Caicedo Zamudio, Antonio Calderón, Claudia T. Gutierrez Villamil, Claudia Jaimes, Juan L. Londono, Nelson Lopez, Sonia Merlano-Gaitan, Ramon Murgieitio-Cabrera, Manuel Valencia, Damiana Vergel, Alejandro Zuluaga Santamaria, Felix Solis, Tonci Batinic, Maja Franceschi, Maja Hrabak Paar, Marina Prpic, Cuba: Juan Felipe Batista, Lazaro Omar Cabrera, Amalia Peix, Yamilé Peña, Luis Manuel Rochela Vázquez, Ioannis Ntalas, Milan Kaminek, Vladimir Kincl, Otto Lang, Jawdat Abdulla, Morten Bøttcher, Martin Busk, Uka Geisler, Lars C. Gormsen, Nicolaj Hansson, Søren Hess, Jens Hove, Lars Thorbjoern Jensen, Magnus T. Jensen, Kristian Hay Kragholm, Bjarne L. Nørgaard, Kristian Øvrehus, Jan Rasmussen, Niels Peter Rønnow Sand, Hanne Sondergaard, Tomas Zaremba, Herwin Speckter, Nelson Amores, Mayra Sanchez Velez, Taghreed Abd Alrahman, Sherif Abd Elsamad, Alia Abdelfattah, Adel Allam, Sameh Elkaffas, Mona Hassan, Elshaymaa Hussein, Ahmed Ibrahim, Ahmed Kandeel, Mohamed Mandour Ali, Mahmoud Shaaban, Camila Flores, Verónica Vanesa Gómez Leiva, Anita Liiver, Martti Larikka, Valtteri Uusitalo, Denis Agostini, Clothilde Berger, Matthieu Dietz, Fabien Hyafil, Mickaël Ohana, Kevin Prigent, Hamza Regaieg, Laure Sarda-Mantel, Darach O. H-Ici, Harold Ayetey, George Angelidis, Christina Fragkaki, Chrysoula Fragkiadaki, Panagiotis Georgoulias, Maria Koutelou, Elena Kyrozi, Niki Lama, Vassilis Prassopoulos, Michael Spartalis, Theodora Zaglavara, Carla Gonzalez, Goleat Gutierrez, Alejandro Maldonado, Yassine Martinez, Attila Kovács, Bálint Szilveszter, Nilesh Banthia, Vivek Bhat, Partha Choudhury, Vijay Sai Chowdekar, Johann Christopher, Tushar Garg, Naresh Kumar Goyal, Ripen Kumar Gupta, Abhishek Gupta, Julie Hephzibah, Shashank Jain, Jesu Krupa, Parveen Kumar, Sukriti Kumar, Arati Lalchandani, Animesh Mishra, Vivaswan Dutt Mishra, Parul Mohan, Ahmad Ozair, Shivani Pandey, Ramanathapuram Parameswaran, Chetan Patel, Tapan Patel, Shivani Patel, Leena Robinson Vimala, Dr Pradosh Kumar Sarangi, Shantanu Sengupta, Arvind Sethi, Amit Sharma, Awadhesh Kumar Sharma, Punit Sharma, Apurva Shrigiriwar, Santosh Singh, Harpreet Singh, Ashwani Sood, Atul Verma, Ajay Vyas, Erwin Affandi Soeriadi, Edison Bun, Febby Hutomo, Hilman Syawaluddin, Ryan Yudistiro, Amjed Albadr, Majid Assadi, Farshad Emami, Alireza Emami-Ardekani, Saeed Farzanehfar, Ramezan Jafari, Reyhaneh Manafi-Farid, Maryam Tajik, Yoav Arnson, Shmuel Fuchs, Ronen Goldkorn, John Kennedy, Marina Leitman, Aryeh Shalev, Wanda Acampa, Domenico Albano, Pierpaolo Alongi, Gaspare Arnone, Roberta Assante, Anna Baritussio, Matteo Bauckneht, Francesco Bianco, Rachele Bonfiglioli, Francesco Bovenzi, Isabella Bruno, Andrea Bruno, Elena Busnardo, Elena Califaretti, Roberta Casoni, Vittorio Censullo, Franca Chierichetti, Marcello Chiocchi, Corrado Cittanti, Alberto Clemente, Alberto Cuocolo, Maria Luisa De Rimini, Giuseppe De Vincentis, Veronica Della Tommasina, Santo Dellegrottaglie, Paola Anna Erba, Laura Evangelista, Lara Faggi, Evelina Faragasso, Luigia Florimonte, Viviana Frantellizzi, Marco Gatti, Angela Gaudiano, Fabrizia Gelardi, Alberto Gerali, Alessia Gimelli, Marco Guglielmo, Lucia Leccisotti, Riccardo Liga, Carlo Liguori, Giampiero Longo, Margherita Maffione, Claudio Marcassa, Giovanni Matassa, Donato Mele, Luca Mircoli, Andrea Paccagnella, Sara Pacella, Federica Padovano, Dario Pellegrini, Valeria Pergola, Luca Pugliese, Natale Quartuccio, Lucia Rampin, Fabrizio Ricci, Giuseppe Rubini, Vincenzo Russo, Gianmario Sambuceti, Alessandra Scatteia, Roberto Sciagrà, Gianluca Spidalieri, Antonella Stefanelli, Carlo Tedeschi, Guido Ventroni, Dainia Baugh, Ernest Madu, Tadao Aikawa, Hiroshi Asano, Shinichiro Fujimoto, Koichiro Fujise, Yoshimitsu Fukushima, Kae Fukuyama, Yasutaka Ichikawa, Reiko Ideguchi, Nobuo Iguchi, Masamichi Imai, Hayato Ishimura, Satoshi Isobe, Kimiteru Ito, Yu Izawa, Toshiaki Kadokami, Tokuo Kasai, Takao Kato, Takashi Kawamoto, Shigeru Kiryu, Shinichiro Kumita, Osamu Manabe, Hirotaka Maruno, Naoya Matsumoto, Masao Miyagawa, Masao Moroi, Shigeki Nagamachi, Kenichi Nakajima, Ryo Nakazato, Mamoru Nanasato, Masanao Naya, Takashi Norikane, Yasutoshi Ohta, Yoichi Otomi, Hideki Otsuka, Noriko Oyama-Manabe, Masaki Saito, Masayoshi Sarai, Junichi Sato, Daisuke Sato, Shinya Shiraishi, Kentaro Takanami, Kazuya Takehana, Yasuyo Taniguchi, Hiroki Teragawa, Nobuo Tomizawa, Kyoko Umeji, Yasushi Wakabayashi, Shinichiro Yamada, Shinya Yamazaki, Tatsuya Yoneyama, Mohammad Rawashdeh, Tairkhan Dautov, Khalid Makhdomi, Mostafa Abass, Masoud Garashi, Qaisar Siraj, Marika Kalnina, Mohamad Haidar, Renata Komiagiene, Giedre Kviecinskiene, Donatas Vajauskas, Noor Khairiah A. Karim, Mady Doucoure, Luise Reichmuth, Anthony Samuel, Mohamed Lemine Dieng, Ambedhkar Shantaram Naojee, Estrella Aguilera Hernandez, Cesar Rene Alducin Tellez, Erick Alexánderson-Rosas, Erika Barragan, Manuel Cabada, Daniel Calderón, Isabel Carvajal-Juarez, José Esparza, Manlio Gerardo Gama-Moreno, Virginia Garcia Quinto, Nelsy Coromoto Gonzalez, Mary Carmen Herrera-Zarza, Aloha Meave, Jesus Gregorio Medina Verdugo, Gabriela Melendez, Rafael Humberto Morales Murguia, Carlos Salvador Navarro Quiroz, Mario Ornelas, Andres Preciado-Anaya, Oscar Ulises Preciado-Gutiérrez, Adriana Puente, Aristóteles Ramírez Salazar, Sandra Graciela Rosales Uvera, Sandra Rosales-Uvera, Jose Antonio Serna Macias, Lilia Sierra-Galan, Lilia M. Sierra-Galan, Juan Carlos Tirado Alderete, Enrique Vallejo, Marc Faraggi, Erdenechimeg Sereegotov, Nouzha Ben Rais, Nadia Ismaili Alaoui, Thiri Kyiphyu, Su Thet Oo, Soe Myat Win, Htin Zar, Ram Ghimire, Madhu Neupane, Andor Glaudemans, Riemer Slart, Derk Verschure, Berry Allen, John Edmond, Clare Mckenzie, Stuart Tie, Niels Van Pelt, Kirsten Worthington, Calum Young, Idrissa Adamou Soli, Shehu Kana, Uchenna Onubogu, Mahmoud Sani, Anders Tjellaug Bråten, Arve Jørgensen, Hanne-Elin Vassbotn, Humoud Al Dhuhli, Zabah Jawa, Naima Tag, Shazia Fatima, Muhammad Babar Imran, Muhammad Numair Younis, Mohammad Saadullah, Yariela Herrera Malo, Dora Lenturut-Katal, Manuel Castillo, José Ortellado, Afroza Akhter, F. Aaysha Cader, Raihan Hussain, Saidur Rahman Khan, Tapati Mandal, Faria Nasreen, Yunqiang An, Dianbo Cao, Lianggeng Gong, Yang Hou, Chongfu Jia, Tao Li, Caiying Li, Hui Liu, Wenya Liu, Jinkang Liu, Ming-Yen Ng, Heshui Shi, Chunxiang Tang, Ximing Wang, Zhaoqian Wang, Yining Wang, Jiang Wu, Yan Yi, Li Yuan, Tong Zhang, Longjiang Zhang, Edith Chavez, Carlos Cruz, Christian Llontop, Rosanna Morales, Paz Abrihan, Asela Bustos-Barroso, Michele Duldulao-Ogbac, Christopher Eduarte, Jerry Obaldo, Alvin Quinon, Belinda San Juan, Carlo Joe San Juan, Marie Rhiamar Sauler-Gomez, Mila Uy, Magdalena Kostkiewicz, Jolanta Kunikowska, Anna Teresinska, Tomasz Urbanik, Nuno Bettencourt, Ricardo Fontes-Carvalho, Cristina Gavina, Lino Gonçalves, Filipe Macedo, Nuno Moreno, Carla Sousa, Ana Teresa Timoteo, Maria João Vidigal, Mahmoud Al Heidous, Subramaniyan Ramanathan, Samer Arnous, Said Aytani, Angela Byrne, Tadhg Gleeson, David Kerins, Julie O'Brien, Ji-In Bang, Henry Bom, Miju Cheon, Gi Jeong Cheon, Sang-Geon Cho, Chae Moon Hong, Yong Hyu Jeong, Won Jun Kang, Yeon-Koo Kang, Ji-Young Kim, So Won Oh, Young So, Ho-Chun Song, Kyoung Sook Won, Soo Woong Yoo, Irena Mitevska, Marija Vavlukis, Barbara Gužic Salobir, Monika Štalc, Theodora Benedek, Marian Pop, Claudiu Stan, Alexey Ansheles, Olga Dariy, Nina Gagarina, Irina Itskovich, Anatoliy Karalkin, Alexander Kokov, Gulya Marina, Ekaterina Migunova, Viktor Pospelov, Daria Ryzhkova, Guzaliya Sayfullina, Vladimir Sergienko, Irina Shurupova, Margarita Vakhromeeva, Nailia Valiullina, Konstantin Zavadovsky, Kirill Zhuravlev, Rami Abazid, Turki Al Garni, Mirvat Alasnag, Ahmed Aljizeeri, Hamid Amer, Ahmad Amro, Hesham Hamdy, Osama Smettei, Dragana Sobic Saranovic, Marina Vlajkovic, Felix Keng, Jason See, Zuzana Berecova, Jana Polakova Mistinova, Osayande Evbuomwan, Nerisha Govender, Jonathan Hack, Bawinile Hadebe, Khanyisile Hlongwa, Mitchell Kaplan, Hoosen Lakhi, Katarina Milos, Moshe Modiselle, Stuart More, Ntanganedzeni Muambadzi, Leonie Scholtz, Manuel Barreiro-Perez, Isabel Blanco, Jordi Broncano, Alicia Camarero, Irene Casáns-Tormo, Javier De Haro, Albert Flotats, Elia García, Ceferino Gutierrez Mendiguchia, Amelia Jimenez-Heffernan, Ruben Leta, Javier Lopez Diaz, Luis Lumbreras Vega, Ana Manovel-Sánchez, Amparo Martinez Monzonis, Bianca Patrut, Virginia Pubul, Ricardo Ruano Perez, Nahla Zeidan, Damayanthi Nanayakkara, Ahmed Suliman, Henrik Engblom, Mustafa Murtadha, Ellen Ostenfeld, Magnus Simonsson, Hatem Alkadhi, Ronny Ralf Buechel, Peter Burger, Christoph Gräni, Christel Kamani, Nadine Kawel-Böhm, Bernd Klaeser, Robert Manka, John Prior, Tawika Kaewchur, Benjapa Khiewvan, Arpakorn Kositwattanarerk, Sirianong Namwongprom, Tanyaluck Thientunyakit, Haluk Burcak Sayman, Mahmut Yüksel, Mugisha Julius Sebikali, Emmy Okello, Pavlo Korol, Iryna Noverko, Maryna Satyr, Tahir Ahmad, Khaled Alfakih, Ivo Andrade, Susan Buckingham, Anda Bularga, John-Paul Carpenter, Graham Cole, David Cusack, Sarojini David, Patrick Davis, Timothy Fairbairn, Arjun Ghosh, Prasad Guntur Ramkumar, Mark Hamilton, Faisal Haque, Benjamin Hudson, Annette Johnstone, V.J. Karthikeyan, Mike Kay, Mohammad Ali Khan, Jamie Kitt, Chen Sheng Low, Elisa Mcalindon, David Mccreavy, Brian Morrissey, Manish Motwani, Dilip Na, Edward Nicol, Dilip Patel, Jonathan Rodrigues, Chris Rofe, Rebecca Schofield, Thomas Semple, Azeem Sheikh, Apurva Sinha, Deepak Subedi, William Topping, Katherine Tweed, Stephen Richard Underwood, Jonathan Weir-Mccall, Hamed Zuhairy, Taimur Abbasi, Shady Abohashem, Sandra Abramson, Mouaz Al-Mallah, Mohan Ashok Kumar, Mallory Balmer-Swain, Daniel Berman, Adam Bernheim, Sabha Bhatti, Robert Biederman, Erik Bieging, Scott Bingham, Stephen Bloom, Sean Blue, Andressa Borges, Kelley Branch, Paco Bravo, Sujatha Buddhe, Matthew Budoff, Renée Bullock-Palmer, Michael Cahill, Candace Candela, Jane Cao, Saurav Chatterjee, Yiannis Chatzizisis, Nita Ray Chaudhuri, Michael Cheezum, Anjali Chelliah, Tiffany Chen, Marcus Chen, Lu Chen, Aalap Chokshi, Jina Chung, Sorin Danciu, William DeSisto, Michael Dilorenzo, Rami Doukky, William Duvall, Maros Ferencik, Cameron Foster, Anthon Fuisz, Michael Gannon, David German, Myron Gerson, Jeffrey Geske, Fadi Hage, Agha Haider, Sofia Haider, Yasmin Hamirani, Karen Hassen, Robert Hendel, Jacqueline Henkel, Stephen Horgan, Mark Hyun, Rajesh Janardhanan, Scott Jerome, Dinesh Kalra, David Kassop, Mona Kinkhabwala, George Kinzfogl, Bernard Koch, Lynne Koweek, Joseph Krepp, Younghoon Kwon, Jay Layer, John Lesser, Steve Leung, Bernadette Lisske, Kathleen Magurany, Jeremy Markowitz, Brenda Mccullough, Azita Moalemi, Chanan Moffitt, Juan Montanez, Warren Moore, Shamil Morayati, Mahmud Mossa-Basha, Zorana Mrsic, Venkatesh Murthy, Prashant Nagpal, Katarina Nelson, Prabhjot Nijjar, Rupal O’Quinn, Edward Passen, Toral Patel, Pravin Patil, Amit Pursnani, Nancy Quachang, Mark Rabbat, Pragya Ranjan, Patricia Rodriguez Lozano, Mary Schemmer, Rebecca Seifried, Nishant Shah, Amee Shah, Sujata Shanbhag, Gaurav Sharma, Robert Skotnicki, Michael Sobczak, Prem Soman, Vincent Sorrell, Monvadi Srichai, Jim Streeter, Leah Strickland, Suliman Suliman, Naghmeh Tebyanian, Dustin Thomas, Randall Thompson, Seth Uretsky, Srikanth Vallurupalli, Marian Vandyck-Acquah, Vikas Verma, Todd Villines, Joseph Weinstein, David Wolinsky, Karolina Zareba, Michael Zgaljardic, Mario Beretta, Rodolfo Ferrando, Miguel Kapitan, Fernando Mut, Omoa Djuraev, Gulnora Rozikhodjaeva, Luisa Vera, Binh Duong Duc, Xuan Canh Nguyen, Phuoc Minh Hiep Nguyen, Translational Immunology Groningen (TRIGR), Cardiovascular Centre (CVC), ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Molecular Pharmacology, Drug Design, Einstein, A, Hirschfeld, C, Williams, M, Vitola, J, Better, N, Villines, T, Cerci, R, Shaw, L, Choi, A, Dorbala, S, Karthikeyan, G, Lu, B, Sinitsyn, V, Ansheles, A, Kudo, T, Bucciarelli-Ducci, C, Norgaard, B, Maurovich-Horvat, P, Campisi, R, Milan, E, Louw, L, Allam, A, Bhatia, M, Sewanan, L, Malkovskiy, E, Cohen, Y, Randazzo, M, Narula, J, Morozova, O, Pascual, T, Pynda, Y, Dondi, M, Paez, D, Hinterleitner, G, Lu, Y, Xu, Z, Erinne, I, Shetty, M, Lopez-Mattei, J, Parwani, P, Goda, A, Shirka, E, Bouyoucef, S, Chelghoum, L, Mansouri, F, Medjahedi, A, Naili, Q, Ridouh, M, Alasia, D, Alberghina, L, Aramayo, N, Buchara, D, Busso, F, Bustos Rivadero, J, Camilletti, J, Campanelli, H, Castro, R, Daicz, M, del Riego, H, Dragonetti, L, Echazarreta, D, Erriest, J, Faccio, F, Facello, A, Gallegos, H, Geronazzo, R, Glait, H, Hasbani, V, Jager, V, Lewkowicz, J, Lotti, J, Maciel, N, Masoli, O, Mastrovito, E, Medus, M, Merani, M, Molteni, S, Montecinos, M, Parisi, G, Sueldo, C, Perez de Arenaza, D, Quintana, L, Radzinschi, A, Redruello, M, Rodriguez, M, Rojas, H, Acuna, A, Schere, D, Traverso, S, Vazquez, G, Zeffiro, S, Sakanyan, M, Beuzeville, S, Boktor, R, Crowley, M, Downie, D, Dwivedi, G, Elison, B, Farouque, O, Jasper, K, Joshi, S, Lee, J, Lee, K, Lui, E, Mcconachie, P, Meaker, J, Nandurkar, D, Neill, J, O'Rourke, E, O'Sullivan, P, Pandos, G, Premaratne, M, Prior, D, Rutherford, N, Saunders, C, Taubman, K, Tauro, A, Taylor, A, Theuerle, J, Thomas, P, Tow, J, Upton, A, Vamadevan, S, Wayne, V, Wegner, E, Wong, D, Younger, J, Beitzke, D, Feuchtner, G, Sommer, O, Weiss, K, Maroz-Vadalazhskaya, N, Tserakhau, U, Homans, F, Van De Heyning, C, Araujo, R, Soldat-Stankovic, V, Stankovic, S, Almeida, A, Anselmi, C, Azevedo, G, Bittencourt, M, Pianta, D, Cabeda, E, Carreira, L, Coelho, I, de Amorim Fernandes, F, de Lorenzo, A, Delgado, R, Erthal, F, Fernandes, F, Fernandes, J, Ferreira de Souza, T, Foppa, M, Matos Alves, W, Gontijo, C, Gottlieb, I, Grossman, G, Albernaz Siqueira, M, Nomura, C, Koga, K, Lima, R, Lopes, R, Marcal Filho, H, Masiero, P, Mastrocola, L, Menezes de Siqueira, M, Mesquita, C, Naves, D, Penna, F, Pinto, I, Rocha, T, Rocha, J, Rodrigues, A, Salioni, L, Sanches, A, Santos, M, Da Silva, L, Schvartzman, P, Matushita, C, Senra, T, Silva, M, Soares, C, Spiro, B, Suaide Silva, C, Torres, R, Monte, G, Vilela, A, Villa, A, Voss, T, Waltrick, R, Zapparoli, M, Naseer, H, Garcheva-Tsacheva, M, Ouattara, T, Thou, S, Varoeun, S, Abikhzer, G, Beanlands, R, Chetrit, M, Dabreo, D, Dennie, C, Friedrich, M, Hafez, M, Hanneman, K, Miller, R, Oikonomou, A, Roifman, I, Small, G, Tandon, V, Trivedi, A, White, J, Zukotynski, K, Alay, R, Concha, C, Massardo, T, Abad, P, Anzola, K, Arturo, H, Benitez, L, Cadena, A, Zamudio, C, Calderon, A, Gutierrez Villamil, C, Jaimes, C, Londono, J, Lopez, N, Merlano-Gaitan, S, Murgieitio-Cabrera, R, Valencia, M, Vergel, D, Santamaria, A, Solis, F, Batinic, T, Franceschi, M, Paar, M, Prpic, M, Felipe Batista, C, Cabrera, L, Peix, A, Pena, Y, Rochela Vazquez, L, Ntalas, I, Kaminek, M, Kincl, V, Lang, O, Abdulla, J, Bottcher, M, Busk, M, Geisler, U, Gormsen, L, Hansson, N, Hess, S, Hove, J, Jensen, L, Jensen, M, Kragholm, K, Ovrehus, K, Rasmussen, J, Ronnow Sand, N, Sondergaard, H, Zaremba, T, Speckter, H, Amores, N, Velez, M, Alrahman, T, Elsamad, S, Abdelfattah, A, Elkaffas, S, Hassan, M, Hussein, E, Ibrahim, A, Kandeel, A, Ali, M, Shaaban, M, Flores, C, Gomez Leiva, V, Liiver, A, Larikka, M, Uusitalo, V, Agostini, D, Berger, C, Dietz, M, Hyafil, F, Ohana, M, Prigent, K, Regaieg, H, Sarda-Mantel, L, H-Ici, D, Ayetey, H, Angelidis, G, Fragkaki, C, Fragkiadaki, C, Georgoulias, P, Koutelou, M, Kyrozi, E, Lama, N, Prassopoulos, V, Spartalis, M, Zaglavara, T, Gonzalez, C, Gutierrez, G, Maldonado, A, Martinez, Y, Kovacs, A, Szilveszter, B, Banthia, N, Bhat, V, Choudhury, P, Chowdekar, V, Christopher, J, Garg, T, Goyal, N, Gupta, R, Gupta, A, Hephzibah, J, Jain, S, Krupa, J, Kumar, P, Kumar, S, Lalchandani, A, Mishra, A, Mishra, V, Mohan, P, Ozair, A, Pandey, S, Parameswaran, R, Patel, C, Patel, T, Patel, S, Vimala, L, Kumar Sarangi, D, Sengupta, S, Sethi, A, Sharma, A, Sharma, P, Shrigiriwar, A, Singh, S, Singh, H, Sood, A, Verma, A, Vyas, A, Soeriadi, E, Bun, E, Hutomo, F, Syawaluddin, H, Yudistiro, R, Albadr, A, Assadi, M, Emami, F, Emami-Ardekani, A, Farzanehfar, S, Jafari, R, Manafi-Farid, R, Tajik, M, Arnson, Y, Fuchs, S, Goldkorn, R, Kennedy, J, Leitman, M, Shalev, A, Acampa, W, Albano, D, Alongi, P, Arnone, G, Assante, R, Baritussio, A, Bauckneht, M, Bianco, F, Bonfiglioli, R, Bovenzi, F, Bruno, I, Bruno, A, Busnardo, E, Califaretti, E, Casoni, R, Censullo, V, Chierichetti, F, Chiocchi, M, Cittanti, C, Clemente, A, Cuocolo, A, De Rimini, M, De Vincentis, G, Della Tommasina, V, Dellegrottaglie, S, Erba, P, Evangelista, L, Faggi, L, Faragasso, E, Florimonte, L, Frantellizzi, V, Gatti, M, Gaudiano, A, Gelardi, F, Gerali, A, Gimelli, A, Guglielmo, M, Leccisotti, L, Liga, R, Liguori, C, Longo, G, Maffione, M, Marcassa, C, Matassa, G, Mele, D, Mircoli, L, Paccagnella, A, Pacella, S, Padovano, F, Pellegrini, D, Pergola, V, Pugliese, L, Quartuccio, N, Rampin, L, Ricci, F, Rubini, G, Russo, V, Sambuceti, G, Scatteia, A, Sciagra, R, Spidalieri, G, Stefanelli, A, Tedeschi, C, Ventroni, G, Baugh, D, Madu, E, Aikawa, T, Asano, H, Fujimoto, S, Fujise, K, Fukushima, Y, Fukuyama, K, Ichikawa, Y, Ideguchi, R, Iguchi, N, Imai, M, Ishimura, H, Isobe, S, Ito, K, Izawa, Y, Kadokami, T, Kasai, T, Kato, T, Kawamoto, T, Kiryu, S, Kumita, S, Manabe, O, Maruno, H, Matsumoto, N, Miyagawa, M, Moroi, M, Nagamachi, S, Nakajima, K, Nakazato, R, Nanasato, M, Naya, M, Norikane, T, Ohta, Y, Otomi, Y, Otsuka, H, Oyama-Manabe, N, Saito, M, Sarai, M, Sato, J, Sato, D, Shiraishi, S, Takanami, K, Takehana, K, Taniguchi, Y, Teragawa, H, Tomizawa, N, Umeji, K, Wakabayashi, Y, Yamada, S, Yamazaki, S, Yoneyama, T, Rawashdeh, M, Dautov, T, Makhdomi, K, Abass, M, Garashi, M, Siraj, Q, Kalnina, M, Haidar, M, Komiagiene, R, Kviecinskiene, G, Vajauskas, D, Karim, N, Doucoure, M, Reichmuth, L, Samuel, A, Dieng, M, Naojee, A, Hernandez, E, Alducin Tellez, C, Alexanderson-Rosas, E, Barragan, E, Cabada, M, Calderon, D, Carvajal-Juarez, I, Esparza, J, Gama-Moreno, M, Quinto, V, Gonzalez, N, Herrera-Zarza, M, Meave, A, Medina Verdugo, J, Melendez, G, Morales Murguia, R, Navarro Quiroz, C, Ornelas, M, Preciado-Anaya, A, Preciado-Gutierrez, O, Puente, A, Salazar, A, Rosales Uvera, S, Rosales-Uvera, S, Serna Macias, J, Sierra-Galan, L, Tirado Alderete, J, Vallejo, E, Faraggi, M, Sereegotov, E, Ben Rais, N, Alaoui, N, Kyiphyu, T, Oo, S, Win, S, Zar, H, Ghimire, R, Neupane, M, Glaudemans, A, Slart, R, Verschure, D, Allen, B, Edmond, J, Mckenzie, C, Tie, S, Van Pelt, N, Worthington, K, Young, C, Soli, I, Kana, S, Onubogu, U, Sani, M, Braten, A, Jorgensen, A, Vassbotn, H, Al Dhuhli, H, Jawa, Z, Tag, N, Fatima, S, Imran, M, Younis, M, Saadullah, M, Malo, Y, Lenturut-Katal, D, Castillo, M, Ortellado, J, Akhter, A, Cader, F, Hussain, R, Khan, S, Mandal, T, Nasreen, F, An, Y, Cao, D, Gong, L, Hou, Y, Jia, C, Li, T, Li, C, Liu, H, Liu, W, Liu, J, Ng, M, Shi, H, Tang, C, Wang, X, Wang, Z, Wang, Y, Wu, J, Yi, Y, Yuan, L, Zhang, T, Zhang, L, Chavez, E, Cruz, C, Llontop, C, Morales, R, Abrihan, P, Bustos-Barroso, A, Duldulao-Ogbac, M, Eduarte, C, Obaldo, J, Quinon, A, San Juan, B, San Juan, C, Sauler-Gomez, M, Uy, M, Kostkiewicz, M, Kunikowska, J, Teresinska, A, Urbanik, T, Bettencourt, N, Fontes-Carvalho, R, Gavina, C, Goncalves, L, Macedo, F, Moreno, N, Sousa, C, Timoteo, A, Vidigal, M, Al Heidous, M, Ramanathan, S, Arnous, S, Aytani, S, Byrne, A, Gleeson, T, Kerins, D, O'Brien, J, Bang, J, Bom, H, Cheon, M, Cheon, G, Cho, S, Hong, C, Jeong, Y, Kang, W, Kang, Y, Kim, J, Oh, S, So, Y, Song, H, Won, K, Yoo, S, Mitevska, I, Vavlukis, M, Salobir, B, Stalc, M, Benedek, T, Pop, M, Stan, C, Dariy, O, Gagarina, N, Itskovich, I, Karalkin, A, Kokov, A, Marina, G, Migunova, E, Pospelov, V, Ryzhkova, D, Sayfullina, G, Sergienko, V, Shurupova, I, Vakhromeeva, M, Valiullina, N, Zavadovsky, K, Zhuravlev, K, Abazid, R, Al Garni, T, Alasnag, M, Aljizeeri, A, Amer, H, Amro, A, Hamdy, H, Smettei, O, Saranovic, D, Vlajkovic, M, Keng, F, See, J, Berecova, Z, Mistinova, J, Evbuomwan, O, Govender, N, Hack, J, Hadebe, B, Hlongwa, K, Kaplan, M, Lakhi, H, Milos, K, Modiselle, M, More, S, Muambadzi, N, Scholtz, L, Barreiro-Perez, M, Blanco, I, Broncano, J, Camarero, A, Casans-Tormo, I, De Haro, J, Flotats, A, Garcia, E, Mendiguchia, C, Jimenez-Heffernan, A, Leta, R, Diaz, J, Vega, L, Manovel-Sanchez, A, Monzonis, A, Patrut, B, Pubul, V, Perez, R, Zeidan, N, Nanayakkara, D, Suliman, A, Engblom, H, Murtadha, M, Ostenfeld, E, Simonsson, M, Alkadhi, H, Buechel, R, Burger, P, Grani, C, Kamani, C, Kawel-Bohm, N, Klaeser, B, Manka, R, Prior, J, Kaewchur, T, Khiewvan, B, Kositwattanarerk, A, Namwongprom, S, Thientunyakit, T, Sayman, H, Yuksel, M, Sebikali, M, Okello, E, Korol, P, Noverko, I, Satyr, M, Ahmad, T, Alfakih, K, Andrade, I, Buckingham, S, Bularga, A, Carpenter, J, Cole, G, Cusack, D, David, S, Davis, P, Fairbairn, T, Ghosh, A, Ramkumar, P, Hamilton, M, Haque, F, Hudson, B, Johnstone, A, Karthikeyan, V, Kay, M, Khan, M, Kitt, J, Low, C, Mcalindon, E, Mccreavy, D, Morrissey, B, Motwani, M, Na, D, Nicol, E, Patel, D, Rodrigues, J, Rofe, C, Schofield, R, Semple, T, Sheikh, A, Sinha, A, Subedi, D, Topping, W, Tweed, K, Underwood, S, Weir-Mccall, J, Zuhairy, H, Abbasi, T, Abohashem, S, Abramson, S, Al-Mallah, M, Kumar, M, Balmer-Swain, M, Berman, D, Bernheim, A, Bhatti, S, Biederman, R, Bieging, E, Bingham, S, Bloom, S, Blue, S, Borges, A, Branch, K, Bravo, P, Buddhe, S, Budoff, M, Bullock-Palmer, R, Cahill, M, Candela, C, Cao, J, Chatterjee, S, Chatzizisis, Y, Chaudhuri, N, Cheezum, M, Chelliah, A, Chen, T, Chen, M, Chen, L, Chokshi, A, Chung, J, Danciu, S, Desisto, W, Dilorenzo, M, Doukky, R, Duvall, W, Ferencik, M, Foster, C, Fuisz, A, Gannon, M, German, D, Gerson, M, Geske, J, Hage, F, Haider, A, Haider, S, Hamirani, Y, Hassen, K, Hendel, R, Henkel, J, Horgan, S, Hyun, M, Janardhanan, R, Jerome, S, Kalra, D, Kassop, D, Kinkhabwala, M, Kinzfogl, G, Koch, B, Koweek, L, Krepp, J, Kwon, Y, Layer, J, Lesser, J, Leung, S, Lisske, B, Magurany, K, Markowitz, J, Mccullough, B, Moalemi, A, Moffitt, C, Montanez, J, Moore, W, Morayati, S, Mossa-Basha, M, Mrsic, Z, Murthy, V, Nagpal, P, Nelson, K, Nijjar, P, O'Quinn, R, Passen, E, Patil, P, Pursnani, A, Quachang, N, Rabbat, M, Ranjan, P, Lozano, P, Schemmer, M, Seifried, R, Shah, N, Shah, A, Shanbhag, S, Sharma, G, Skotnicki, R, Sobczak, M, Soman, P, Sorrell, V, Srichai, M, Streeter, J, Strickland, L, Suliman, S, Tebyanian, N, Thomas, D, Thompson, R, Uretsky, S, Vallurupalli, S, Vandyck-Acquah, M, Verma, V, Weinstein, J, Wolinsky, D, Zareba, K, Zgaljardic, M, Beretta, M, Ferrando, R, Kapitan, M, Mut, F, Djuraev, O, Rozikhodjaeva, G, Vera, L, Duc, B, Nguyen, X, Hiep Nguyen, P, Einstein, Andrew J, Hirschfeld, Cole, Williams, Michelle C, Vitola, Joao V, Better, Nathan, Villines, Todd C, Cerci, Rodrigo, Shaw, Leslee J, Choi, Andrew D, Dorbala, Sharmila, Karthikeyan, Ganesan, Lu, Bin, Sinitsyn, Valentin, Ansheles, Alexey A, Kudo, Takashi, Bucciarelli-Ducci, Chiara, Nørgaard, Bjarne Linde, Maurovich-Horvat, Pál, Campisi, Roxana, Milan, Elisa, Louw, Lizette, Allam, Adel H, Bhatia, Mona, Sewanan, Lorenzo, Malkovskiy, Eli, Cohen, Yosef, Randazzo, Michael, Narula, Jagat, Morozova, Olga, Pascual, Thomas N B, Pynda, Yaroslav, Dondi, Maurizio, Paez, Diana, and Cuocolo, Alberto

Subjects
cardiac testing, Health Personnel, delivery of health care, coronavirus, COVID-19, global health, 610 Medicine & health, cardiovascular disease, health personnel, humans, pandemics, surveys and questionnaires, coronaviru, Surveys and Questionnaires, Humans, Cardiology and Cardiovascular Medicine, Delivery of Health Care, Pandemics, COVID-19/epidemiology
Abstract

BACKGROUND: The extent to which health care systems have adapted to the COVID-19 pandemic to provide necessary cardiac diagnostic services is unknown.OBJECTIVES: The aim of this study was to determine the impact of the pandemic on cardiac testing practices, volumes and types of diagnostic services, and perceived psychological stress to health care providers worldwide.METHODS: The International Atomic Energy Agency conducted a worldwide survey assessing alterations from baseline in cardiovascular diagnostic care at the pandemic's onset and 1 year later. Multivariable regression was used to determine factors associated with procedure volume recovery.RESULTS: Surveys were submitted from 669 centers in 107 countries. Worldwide reduction in cardiac procedure volumes of 64% from March 2019 to April 2020 recovered by April 2021 in high- and upper middle-income countries (recovery rates of 108% and 99%) but remained depressed in lower middle- and low-income countries (46% and 30% recovery). Although stress testing was used 12% less frequently in 2021 than in 2019, coronary computed tomographic angiography was used 14% more, a trend also seen for other advanced cardiac imaging modalities (positron emission tomography and magnetic resonance; 22%-25% increases). Pandemic-related psychological stress was estimated to have affected nearly 40% of staff, impacting patient care at 78% of sites. In multivariable regression, only lower-income status and physicians' psychological stress were significant in predicting recovery of cardiac testing.CONCLUSIONS: Cardiac diagnostic testing has yet to recover to prepandemic levels in lower-income countries. Worldwide, the decrease in standard stress testing is offset by greater use of advanced cardiac imaging modalities. Pandemic-related psychological stress among providers is widespread and associated with poor recovery of cardiac testing.

Published
2022

8. Long-term safety and efficacy of tezacaftor–ivacaftor in individuals with cystic fibrosis aged 12 years or older who are homozygous or heterozygous for Phe508del CFTR (EXTEND): an open-label extension study

Author

Patrick A Flume, Reta Fischer Biner, Damian G Downey, Cynthia Brown, Manu Jain, Rainald Fischer, Kris De Boeck, Gregory S Sawicki, Philip Chang, Hildegarde Paz-Diaz, Jaime L Rubin, Yoojung Yang, Xingdi Hu, David J Pasta, Stefanie J Millar, Daniel Campbell, Xin Wang, Neil Ahluwalia, Caroline A Owen, Claire E Wainwright, Ronald L. Gibson, Steven M. Rowe, Noah Lechtzin, Richard C. Ahrens, Karen S. McCoy, Moira Aitken, Scott H. Donaldson, Kimberly Ann McBennett, Joseph M. Pilewski, Joanne Billings, Carlos Milla, Ronald Rubenstein, Daniel Brian Rosenbluth, Rachel Linnemann, Michael R. Powers, Christopher Fortner, Carla Anne Frederick, Theodore G. Liou, Philip Black, Janice Wang, John L. Colombo, Maria Berdella, Maria Veronica Indihar, Cynthia D. Brown, Michael Anstead, Lara Bilodeau, Leonard Sicilian, James Jerome Tolle, Kathryn Moffett, Samya Nasr, Jennifer Taylor-Cousar, Tara Lynn Barto, Nicholas Antos, John S. Rogers, Bryon Quick, Henry R. Thompson, Gregory Sawicki, Bruce Barnett, Robert L. Zanni, Thomas C. Smith, Karen D. Schultz, Claire Keating, Patrick Flume, Gregory J. Omlor, Alix Ashare, Karen Voter, Nighat Mehdi, Maria Gabriela Tupayachi Ortiz, Tonia E. Gardner, Steven R. Boas, Barbara Messore, Edith Zemanick, Raksha Jain, Michael McCarthy, Dana G. Kissner, Kapilkumar Patel, John McNamara, Julie Philley, Ariel Berlinski, Francisco J. Calimano, Terry Chin, Douglas Conrad, Cori Daines, Hengameh H. Raissy, Thomas G. Keens, Jorge E. Lascano, Bennie McWilliams, Brian Morrissey, Santiago Reyes, Subramanyam Chittivelu, Sabiha Hussain, Arvey Stone, James Wallace, Ross Klingsberg, Julie A. Biller, Stephanie Bui, Olaf Sommerburg, Elisabetta Bignamini, Mirella Collura, Alexander Moller, Donatello Salvatore, Chantal Belleguic, Lea Bentur, Ori Efrati, Eitan Kerem, Dario Prais, Esther Quintana Gallego, Peter Barry, Galit Livnat-Levanon, Jose Ramon Villa Asensi, David Stuart Armstrong, Oscar Asensio de la Cruz, Francis Gilchrist, Diana Elizabeth Tullis, Bradley Quon, Larry C. Lands, Nancy Morrison, Annick Lavoie, Barry Linnane, Okan Elidemir, Felix Ringshausen, Matthias Kappler, Helge Hebestreit, Jochen Mainz, Alexander Kiefer, Cordula Koerner-Rettberg, Doris Staab, Wolfgang Gleiber, Tacjana Pressler, Florian Stehling, Andreas Hector, Sivagurunathan Sutharsan, Lutz Naehrlich, Damian Downey, Jane Carolyn Davies, Robert Ian Ketchell, Mary Patricia Carroll, Simon Doe, Gordon MacGregor, Edward Fairbairn Nash, Nicholas Withers, Daniel Gavin Peckham, Martin James Ledson, Sonal Kansra, Timothy William Rayner Lee, Bertrand Delaisi, Gilles Rault, Jean Le Bihan, Dominique Hubert, Isabelle Fajac, Isabelle Sermet-Gaudelus, Marleen Bakker, Bert Arets, Christiane De Boeck, Raphael Chiron, Philippe Reix, Catherine Mainguy, Eva van Braeckel, Anne Malfroot, Isabelle Durieu, Nadine Desmazes Dufeu, Anne Prevotat, Renske van der Meer, Petrus Merkus, E.J.M. Weersink, Isabel Barrio Gomez-Aguero, Silvia Gartner, Amparo Sole Jover, Antonio Alvarez Fernandez, Desmond William Cox, Edward F. McKone, Barry James Plant, Hiranjan Selvadurai, Simon David Bowler, Claire Elizabeth Wainwright, Daniel Smith, Peter Gordon Middleton, John William Wilson, Sonia Volpi, Carla Colombo, Benedetta Fabrizzi, Vincenzina Lucidi, Federico Cresta, Salvatore Cucchiara, Ernst Eber, Helmut Ellemunter, Isidor Huttegger, Lena Hjelte, Christina Krantz, Marita Gilljam, and Pulmonology

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Indoles, Cystic Fibrosis, Cystic Fibrosis Transmembrane Conductance Regulator, Quinolones, Aminophenols, Cystic fibrosis, Time, Ivacaftor, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Internal medicine, medicine, Clinical endpoint, Humans, Benzodioxoles, 030212 general & internal medicine, Israel, biology, business.industry, Australia, medicine.disease, Cystic fibrosis transmembrane conductance regulator, Discontinuation, Europe, Drug Combinations, Treatment Outcome, Clinical research, 030228 respiratory system, Tolerability, Mutation, North America, biology.protein, Female, business, medicine.drug
Abstract

Summary Background Tezacaftor–ivacaftor is an approved cystic fibrosis transmembrane conductance regulator (CFTR) modulator shown to be efficacious and generally safe and well tolerated over 8–24 weeks in phase 3 clinical studies in participants aged 12 years or older with cystic fibrosis homozygous for the Phe508del CFTR mutation (F/F; study 661-106 [EVOLVE]) or heterozygous for the Phe508del CFTR mutation and a residual function mutation (F/RF; study 661-108 [EXPAND]). Longer-term (>24 weeks) safety and efficacy of tezacaftor–ivacaftor has not been assessed in clinical studies. Here, we present results of study 661-110 (EXTEND), a 96-week open-label extension study that assessed long-term safety, tolerability, and efficacy of tezacaftor–ivacaftor in participants aged 12 years or older with cystic fibrosis who were homozygous or heterozygous for the Phe508del CFTR mutation. Methods Study 661-110 was a 96-week, phase 3, multicentre, open-label study at 170 clinical research sites in Australia, Europe, Israel, and North America. Participants were aged 12 years or older, had cystic fibrosis, were homozygous or heterozygous for Phe508del CFTR, and completed one of six parent studies of tezacaftor–ivacaftor: studies 661-103, 661-106, 661-107, 661-108, 661-109, and 661-111. Participants received oral tezacaftor 100 mg once daily and oral ivacaftor 150 mg once every 12 h for up to 96 weeks. The primary endpoint was safety and tolerability. Secondary endpoints were changes in lung function, nutritional parameters, and respiratory symptom scores; pulmonary exacerbations; and pharmacokinetic parameters. A post-hoc analysis assessed the rate of lung function decline in F/F participants who received up to 120 weeks of tezacaftor–ivacaftor in studies 661-106 (F/F) and/or 661-110 compared with a matched cohort of CFTR modulator-untreated historical F/F controls from the Cystic Fibrosis Foundation Patient Registry. Primary safety analyses were done in all participants from all six parent studies who received at least one dose of study drug during this study. This study was registered at ClinicalTrials.gov ( NCT02565914 ). Findings Between Aug 31, 2015, to May 31, 2019, 1044 participants were enrolled in study 661-110 from the six parent studies of whom 1042 participants received at least one dose of study drug and were included in the safety set. 995 (95%) participants had at least one TEAE; 22 (2%) had TEAEs leading to discontinuation; and 351 (34%) had serious TEAEs. No deaths occurred during the treatment-emergent period; after the treatment-emergent period, two deaths occurred, which were both deemed unrelated to study drug. F/F (106/110; n=459) and F/RF (108/110; n=226) participants beginning tezacaftor–ivacaftor in study 661-110 had improvements in efficacy endpoints consistent with parent studies; improvements in lung function and nutritional parameters and reductions in pulmonary exacerbations observed in the tezacaftor–ivacaftor groups in the parent studies were generally maintained in study 661-110 for an additional 96 weeks. Pharmacokinetic parameters were also similar to those in the parent studies. The annualised rate of lung function decline was 61·5% (95% CI 35·8 to 86·1) lower in tezacaftor–ivacaftor-treated F/F participants versus untreated matched historical controls. Interpretation Tezacaftor–ivacaftor was generally safe, well tolerated, and efficacious for up to 120 weeks, and the safety profile of tezacaftor–ivacaftor in study 661-110 was consistent with cystic fibrosis manifestations and with the safety profiles of the parent studies. The rate of lung function decline was significantly reduced in F/F participants, consistent with cystic fibrosis disease modification. Our results support the clinical benefit of long-term tezacaftor–ivacaftor treatment for people aged 12 years or older with cystic fibrosis with F/F or F/RF genotypes. Funding Vertex Pharmaceuticals Incorporated.

Published
2021

9. A LC–MS/MS platform for the identification of productivity markers in industrial mammalian cell culture media

Author

Lelia Riordan, David Hawe, Sean Forestell, Brian Morrissey, Simone Albrecht, Anna Lindeberg, Nicola McGillicuddy, Christian Kaisermayer, Jonathan Bones, and Patrick Floris

Subjects
0106 biological sciences, 0303 health sciences, Chromatography, Dipeptide, Chemistry, Hydrophilic interaction chromatography, Bioengineering, Cell culture media, 01 natural sciences, Applied Microbiology and Biotechnology, Biochemistry, Hydrolysate, 03 medical and health sciences, chemistry.chemical_compound, Cell culture, 010608 biotechnology, Lc ms ms, Principal component analysis, Bioprocess, 030304 developmental biology
Abstract

Cell culture media formulations supplemented with soy hydrolysates for commercial scale manufacturing of therapeutic proteins were characterized by high-resolution LC–MS/MS to identify specific media components that contributed to cellular bioprocess variability. Initial untargeted screening of media formulations resulted in the combined quantification of >2500 features upon analysis by reversed-phase and hydrophilic interaction liquid chromatography. Chemometric evaluation of quantified features by Principal Component Analysis and Hierarchical Clustering revealed clear correlation between media lots and the corresponding hydrolysates implemented during formulation development stages, suggesting that the observed variation in culture performance could be influenced by components present within hydrolysates. Through multivariate data analysis, a small number of dipeptides, identified as Tyrosyl-Leucine, Phenylalanyl-Valine and LL-Cyclo(Leucylprolyl) were determined in media as potential contributors to bioprocess variability due to their statistically significant higher abundance in formulations which yielded low cellular productivity. Subsequent quantification of these features was performed through targeted LC-QQQ-MS/MS which however, revealed discrepancies between dipeptide concentration levels in media and corresponding hydrolysates presumably due to their potential instability upon interaction with other chemically defined components such as metals or chelating agents. The nutritional impact of the aforementioned features of interest on CHO cell growth performance was assessed through spiking studies in representative shake-flask cultures which however, failed to demonstrate clear correlation between dipeptide concentrations and achieved product yields further indicating the presence of a plausible synergetic effect between the identified dipeptides and alternative media components.

Published
2019

10. 40 A protein biomarker model for detection of cardiac arrhythmia and prediction of associated heart failure

Author

Christopher A. Watson, Cathy Rooney, Claire Tonry, John A. Baugh, Mark Ledwidge, Brian Morrissey, Kenneth McDonald, Stephen R. Pennington, B Herandez, and N Glezeva

Subjects
medicine.medical_specialty, business.industry, A protein, Cardiac arrhythmia, medicine.disease, Heart failure, Internal medicine, Cohort, cardiovascular system, medicine, Cardiology, Biomarker (medicine), Cardiovascular Injury, cardiovascular diseases, business, Adverse effect, Stroke
Abstract

Introduction Cardiac arrhythmia is strongly linked with heart failure (HF) and a primary cause of stroke. The condition affects around 37,000 people in Northern Ireland although it is estimated that many thousands more remain undiagnosed. It is important to be able to diagnose cardiac arrhythmia early, so that appropriate interventions can be made to reduce risk of subsequent stroke or HF. Currently, diagnosis and management of cardiac arrhythmia is reliant on assessment of clinical risk factors, however, routine monitoring of circulating biomarkers would significantly improve accuracy for prediction of arrhythmia and associated adverse events. The aim of this study was to (i) identify protein biomarkers, which can predict cardiac arrhythmia and (ii) identify protein biomarkers that are predictive of HF in patients with arrhythmia. Methods Multiple Reaction Monitoring mass spectrometry-based assays were developed for measurement of a selection of candidate protein biomarkers of cardiovascular injury. Assays were developed using nanoflow reverse phase C18 chromatographic ChipCube based separation, coupled to an Agilent 6460 triple quadrupole mass spectrometer. Optimised MRM assays were applied, in a sample blinded manner, for analysis of a cohort of 410 serum samples. This included 112 patients with cardiac arrhythmia as well as matched controls without cardiac arrhythmia. Results MRM assays were established for measurement of 25 proteins. Individually, a number of the biomarker proteins show significant differential expression between patients with and without cardiac arrhythmia. An 11-protein biomarker model was identified, which was comparable to BNP in prediction of HF within the cardiac arrhythmia subset of patients (Protein panel AUC = 0.856 vs BNP AUC = 0.838). Combination of the 11 proteins with BNP notably enhanced the predictive capacity of BNP (AUC = 0.898). Conclusions/Implications Through this study, assays have been developed for robust, multiplexed measurement of 25 cardiovascular disease-associated proteins in patient serum samples. A number of proteins were identified, which show significant expression changes in association with cardiac arrhythmia and will be further explored. Importantly, a statistical model revealed a panel of 11 proteins, which can predict HF in patients with cardiac arrhythmia, with comparable accuracy to BNP. This panel will need to be further validated in independent patient cohorts.

Published
2020

11. Effect of Zephyr Endobronchial Valves on Dyspnea, Activity Levels, and Quality of Life at One Year. Results from a Randomized Clinical Trial

Author

Mark T. Dransfield, Justin L. Garner, Surya P. Bhatt, Dirk-Jan Slebos, Karin Klooster, Frank C. Sciurba, Pallav L. Shah, Nathaniel T. Marchetti, Richard D. Sue, Shawn Wright, Hiram Rivas-Perez, Tanya A. Wiese, Momen M. Wahidi, Hugo Goulart de Oliveira, Brian Armstrong, Sri Radhakrishnan, Narinder S. Shargill, Gerard J. Criner, Lewis Katz, Francis Cordova, Parag Desai, Nathaniel Marchetti, Victor Kim, Kartik Shenoy, John Travaline, Jiji Thomas, Lii-Yoong H. Criner, Richard Sue, Aaron Thornburg, Terry Thomas, Mark Dransfield, Surya Bhatt, James Michael Wells, Necole Seabron-Harris, Umair Gauhar, Crissie Despirito, Frank Sciurba, Jessica Bon Field, Divay Chandra, Joseph Leader, Roy Semaan, Christina Ledezma, Pallav Shah, Samuel Kemp, Justin Garner, Arafa Aboelhassan, Karthi Srikanthan, Eric Tenda, Anita Abraham, Cai Sim, Momen Wahidi, Kamran Mahmood, Scott Shofer, Kathleen Coles, Guilherme Augusto Oliveira, Betina Machado, Igor Benedetto, Fabio Svartman, Amarilio de Macedo Neto, Leonardo Schreiner, Taiane Vieira, Brian Morrissey, Ken Yoneda, Tina Tham, Daniel Tompkins, Paulo F. Guerreiro Cardoso, Rodrigo Athanazio, Felipe Nominando, Samia Rached, Luciana Cassimiro, Steven Hays, Eric Seeley, Pavan Shrestha, Gabriela R. Dincheva, Adnan Majid, Daniel Alape-Moya, Mihir Parikh, Alichia Paton, Alexis Agnew, Nicholas Pastis, Charlie Strange, Tatsiana Beiko, Danielle Woodford, Mary Blanton, Lisa Kopas, Timothy Connolly, Jose Fernando Santacruz, Bhavin Shah, Mark Vollenweider, Luis Herrera, Rumi Khan, Kristine Sernulka, P. Michael McFadden, Richard Barbers, Michelle Hernandez, Michael Machuzak, Francisco Almeida, Joseph Cicenia, Thomas Gildea, Atul Mehta, Sonali Sethi, Yvonne Meli, David Hsia, Richard Casaburi, William Stringer, Leticia Diaz, Arthur Sung, Meghan Ramsey, Ryan Van Wert, Karen Morris, Nabil Jarad, Tim Batchelor, Iara Sequeiros, Katy Tucker, Malgorzata Kornaszweska, Hazem Fallouh, Ramsey Sabit, Hatam Naase, Joseph George, Azin Salimian, Helen Dyer, Stephen Hazelrigg, Kristal Adams, Karen Bade, Ganesh Krishna, Bryan S. Benn, Michelle Canfield, Sharmila Vetri Villalan, Travis Stewart, Dirk-Ja n Slebos, Nick H. T. ten Hacken, Jorine Hartman, Sonja Augustijn, and Groningen Research Institute for Asthma and COPD (GRIAC)

Subjects
Male, Exacerbation, medicine.medical_treatment, EMPHYSEMA, Bronchoscopic lung volume reduction, law.invention, 0302 clinical medicine, Randomized controlled trial, Quality of life, law, Forced Expiratory Volume, Surveys and Questionnaires, interventional bronchoscopy, Medicine, PREDICTS MORTALITY, 030212 general & internal medicine, LUNG-VOLUME-REDUCTION, Pneumonectomy, Zephyr Valve, Lung function, Original Research, Rehabilitation, Exercise Tolerance, Patient-centered outcomes, Prostheses and Implants, respiratory system, Middle Aged, Treatment Outcome, Pulmonary Emphysema, patient-reported outcomes, Anesthesia, Female, Pulmonary and Respiratory Medicine, REHABILITATION, Adult, Bronchi, Severe copd, OBSTRUCTIVE PULMONARY-DISEASE, CAPACITY, chronic obstructive pulmonary disease, 03 medical and health sciences, severe emphysema, SEVERE COPD, Bronchoscopy, PATIENT-CENTERED OUTCOMES, Humans, Aged, business.industry, respiratory tract diseases, PHYSICAL-ACTIVITY, 030228 respiratory system, EXACERBATION, Quality of Life, business, Adult Pulmonary
Abstract

Rationale: Bronchoscopic lung volume reduction with Zephyr Valves improves lung function, exercise tolerance, and quality of life of patients with hyperinflated emphysema and little to no collateral ventilation. Objectives: Post hoc analysis of patient-reported outcomes (PROs), including multidimensional measures of dyspnea, activity, and quality of life, in the LIBERATE (Lung Function Improvement after Bronchoscopic Lung Volume Reduction with Pulmonx Endobronchial Valves used in Treatment of Emphysema) study are reported. Methods: A total of 190 patients with severe heterogeneous emphysema and little to no collateral ventilation in the target lobe were randomized 2:1 to the Zephyr Valve or standard of care. Changes in PROs at 12 months in the two groups were compared: dyspnea with the Transitional Dyspnea Index (TDI), focal score; the Chronic Obstructive Pulmonary Disease Assessment Test (CAT; breathlessness on hill/stairs); Borg; the EXAcerbations of Chronic pulmonary disease Tool–PRO, dyspnea domain; activity with the TDI, magnitude of task/effort/functional impairment, CAT (limited activities), and the St. George’s Respiratory Questionnaire (SGRQ), activity domain; and psychosocial status with the SGRQ, impacts domain, and CAT (confidence and energy). Results: At 12 months, patients using the Zephyr Valve achieved statistically significant and clinically meaningful improvements in the SGRQ; CAT; and the TDI, focal score, compared with standard of care. Improvements in the SGRQ were driven by the impacts and activity domains (P

Published
2020

12. Phase 2 trial of the DPP-1 inhibitor brensocatib in bronchiectasis

Author

Chalmers, J. D., Haworth, C. S., Metersky, M. L., Loebinger, M. R., Blasi, F., Sibila, O., O'Donnell, A. E., Sullivan, E. J., Mange, K. C., Fernandez, C., Zou, J., Simon D Bowler, Daley C. L., Michael, Chia, Hugh, Greville, Lucy, C Morgan, Siobhain, Mulrennan, Daniel, J Smith, Francis, Thien, Rachel, Thomson, John, Wilson, Natalie, Lorent, Damyan, Arabadzhiev, Mariya, Dimitrova-Georgieva, Ivan, Kiselov, Christo, Terziev, Karen Elisabeth Martha Bendstrup, Christian, N Meyer, Charlotte, Ulrik, Andres, Deroux, Andreas, Eich, Joachim, Ficker, Wolfgang, Gleiber, Christian, Herzmann, Anneliese, Linnhoff, Pontus, Mertsch, Mathias, Pletz, Sivagurunathan, Sutharsan, Francesco, Blasi, Angelo Guido Corsico, Alberto, Pesci, Celi, Alessandro, Mauro, Maniscalco, G Boersma, W, Michiel de Vries, Monique, Reijers, Simone Van der Sar, Benedict, Brockway, Daniel, Garner, John, Kolbe, Catherina, Chang, Paul, Noonan, Adam, Antczak, Elzbieta, Hajoł, Grazyna, Jasieniak-Pinis, Marcin, Bukowczan, Piotr, Napora, Mariko, Koh, Sung Hwan Jeong, Jusang, Kim, Yu-Ii, Kim, Chang-Hoon, Lee, Sook-Young, Lee, Sang Haak Lee, Jeong-Seon, Ryu, Tae Sun Shim, Kwang-Ha, Yoo, Jordi, Dorca, Oriol, Sibila, Antoni, Torres, Rosario, Menendez, Montserrat, Vendrell, Zoe, Borrill, James, Chalmers, Dilip, Nazareth, Richard, Carter, Charles, Haworth, Monica, Nordstrom, Mary, Carroll, Michael, Loebinger, Tarek, Saba, Pinak, Acharya, Ivan, F Ackerman, Idalia, A Acosta, Doreen, Addrizzo-Harris, Juzar, Ali, Francis, Averill, Linda, Barr, Wissam, Chatila, Daniel, Dorgan, Rodney, Folz, Douglas, Hornick, Shijing, Jia, Ryan, Klein, Jorge, Lascano, Rabih, Loutfi, Peadar, Noone, Pamela, Mcshane, Mark, L Metersky, Brian, Morrissey, Anne, O'Donnell, Robert, Orr, Maria Gabriela Tupayachi Ortiz, Julie, Philley, Stephen, Ruoss, Stephen, Ryan, Salma, Saiger, Barry, Sigal, George, Solomon, Colin, Swenson, Ziad, Tannous, Fred, Umeh, and Kevin, L Winthrop

Subjects
Adult, Male, Proteases, 030204 cardiovascular system & hematology, Neutrophilic inflammation, Cathepsin C, Serine, Dose-Response Relationship, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Forced Expiratory Volume, 80 and over, Medicine, Humans, 030212 general & internal medicine, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases, Aged, Aged, 80 and over, Benzoxazoles, Bronchiectasis, Dose-Response Relationship, Drug, business.industry, Elastase, Disease progression, Sputum, General Medicine, Middle Aged, medicine.disease, Disease Progression, Female, Leukocyte Elastase, Serine Proteases, Oxazepines, Multicenter study, Immunology, Drug, business
Abstract

Patients with bronchiectasis have frequent exacerbations that are thought to be related to neutrophilic inflammation. The activity and quantity of neutrophil serine proteases, including neutrophil elastase, are increased in the sputum of patients with bronchiectasis at baseline and increase further during exacerbations. Brensocatib (INS1007) is an oral reversible inhibitor of dipeptidyl peptidase 1 (DPP-1), an enzyme responsible for the activation of neutrophil serine proteases.In a phase 2, randomized, double-blind, placebo-controlled trial, we randomly assigned, in a 1:1:1 ratio, patients with bronchiectasis who had had at least two exacerbations in the previous year to receive placebo, 10 mg of brensocatib, or 25 mg of brensocatib once daily for 24 weeks. The time to the first exacerbation (primary end point), the rate of exacerbations (secondary end point), sputum neutrophil elastase activity, and safety were assessed.Of 256 patients, 87 were assigned to receive placebo, 82 to receive 10 mg of brensocatib, and 87 to receive 25 mg of brensocatib. The 25th percentile of the time to the first exacerbation was 67 days in the placebo group, 134 days in the 10-mg brensocatib group, and 96 days in the 25-mg brensocatib group. Brensocatib treatment prolonged the time to the first exacerbation as compared with placebo (P = 0.03 for 10-mg brensocatib vs. placebo; P = 0.04 for 25-mg brensocatib vs. placebo). The adjusted hazard ratio for exacerbation in the comparison of brensocatib with placebo was 0.58 (95% confidence interval [CI], 0.35 to 0.95) in the 10-mg group (P = 0.03) and 0.62 (95% CI, 0.38 to 0.99) in the 25-mg group (P = 0.046). The incidence-rate ratio was 0.64 (95% CI, 0.42 to 0.98) in the 10-mg group, as compared with placebo (P = 0.04), and 0.75 (95% CI, 0.50 to 1.13) in the 25-mg group, as compared with placebo (P = 0.17). With both brensocatib doses, sputum neutrophil elastase activity was reduced from baseline over the 24-week treatment period. The incidence of dental and skin adverse events of special interest was higher with the 10-mg and 25-mg brensocatib doses, respectively, than with placebo.In this 24-week trial, reduction of neutrophil serine protease activity with brensocatib in patients with bronchiectasis was associated with improvements in bronchiectasis clinical outcomes. (Funded by Insmed; WILLOW ClinicalTrials.gov number, NCT03218917.).

Published
2020

13. A Multicenter Randomized Controlled Trial of Zephyr Endobronchial Valve Treatment in Heterogeneous Emphysema (LIBERATE)

Author

Gerard J. Criner, Richard Sue, Shawn Wright, Mark Dransfield, Hiram Rivas-Perez, Tanya Wiese, Frank C. Sciurba, Pallav L. Shah, Momen M. Wahidi, Hugo Goulart de Oliveira, Brian Morrissey, Paulo F. G. Cardoso, Steven Hays, Adnan Majid, Nicholas Pastis, Lisa Kopas, Mark Vollenweider, P. Michael McFadden, Michael Machuzak, David W. Hsia, Arthur Sung, Nabil Jarad, Malgorzata Kornaszewska, Stephen Hazelrigg, Ganesh Krishna, Brian Armstrong, Narinder S. Shargill, Dirk-Jan Slebos, Francis Cordova, Parag Desai, Nathaniel Marchetti, Victor Kim, Kartik Shenoy, John Travaline, Jiji Thomas, Lii-Yoong H. Criner, Aaron Thornburg, Terry Thomas, Surya Bhatt, James Michael Wells, Necole Seabron-Harris, Umair Gauhar, Crissie Despirito, Frank Sciurba, Jessica Bon Field, Divay Chandra, Joseph Leader, Roy Semaan, Christina Ledezma, Pallav Shah, Samuel Kemp, Justin Garner, Arafa Aboelhassan, Karthi Srikanthan, Eric Tenda, Anita Abraham, Cai Sim, Momen Wahidi, Kamran Mahmood, Scott Shofer, Kathleen Coles, Guilherme Augusto Oliveira, Betina Machado, Igor Benedetto, Fabio Svartman, Amarilio de Macedo Neto, Leonardo Schreiner, Taiane Vieira, Ken Yoneda, Tina Tham, Daniel Tompkins, Paulo F. Guerreiro Cardoso, Rodrigo Athanazio, Felipe Nominando, Samia Rached, Luciana Cassimiro, Eric Seeley, Pavan Shrestha, Gabriela R. Dincheva, Daniel Alape-Moya, Mihir Parikh, Alichia Paton, Alexis Agnew, Charlie Strange, Tatsiana Beiko, Danielle Woodford, Mary Blanton, Timothy Connolly, Jose Fernando Santacruz, Bhavin Shah, Luis Herrera, Rumi Khan, Kristine Sernulka, Richard Barbers, Michelle Hernandez, Francisco Almeida, Joseph Cicenia, Thomas Gildea, Atul Mehta, Sonali Sethi, Yvonne Meli, David Hsia, Richard Casaburi, William Stringer, Leticia Diaz, Meghan Ramsey, Ryan Van Wert, Karen Morris, Tim Batchelor, Iara Sequeiros, Katy Tucker, Malgorzata Kornaszweska, Hazem Fallouh, Ramsey Sabit, Hatam Naase, Joseph George, Azin Salimian, Helen Dyer, Kristal Adams, Karen Bade, Bryan S. Benn, Michelle Canfield, Sharmila Vetri Villalan, Travis Stewart, Nick H. T. ten Hacken, Karin Klooster, Jorine Hartman, Sonja Augustijn, and Groningen Research Institute for Asthma and COPD (GRIAC)

Subjects
Male, Pulmonary and Respiratory Medicine, CLINICAL-OUTCOMES, medicine.medical_specialty, Randomization, SURGERY, lung reduction, Bronchi, Critical Care and Intensive Care Medicine, OBSTRUCTIVE PULMONARY-DISEASE, chronic obstructive pulmonary disease, MEDICAL THERAPY, Collateral ventilation, law.invention, 03 medical and health sciences, 0302 clinical medicine, Primary outcome, Randomized controlled trial, law, Forced Expiratory Volume, Surveys and Questionnaires, Internal medicine, Bronchoscopy, Correspondence, Humans, COPD, Medicine, 030212 general & internal medicine, LUNG-VOLUME-REDUCTION, Respiratory system, Exercise Tolerance, IMPORTANT DIFFERENCE, business.industry, Walk distance, OPERATIVE MORTALITY, Endobronchial valve, Equipment Design, Prostheses and Implants, Middle Aged, NATIONAL EMPHYSEMA, medicine.disease, Treatment Outcome, emphysema, Pulmonary Emphysema, 030228 respiratory system, TESTS, Female, business
Abstract

Rationale: This is the first multicenter randomized controlled trial to evaluate the effectiveness and safety of Zephyr Endobronchial Valve (EBV) in patients with little to no collateral ventilation out to 12 months.Objectives: To evaluate the effectiveness and safety of Zephyr EBV in heterogeneous emphysema with little to no collateral ventilation in the treated lobe.Methods: Subjects were enrolled with a 2:1 randomization (EBV/standard of care [SoC]) at 24 sites. Primary outcome at 12 months was the Delta EBV-SoC of subjects with a post-bronchodilator FEV1 improvement from baseline of greater than or equal to 15%. Secondary endpoints included absolute changes in post-bronchodilator FEV1, 6-minute-walk distance, and St. George's Respiratory Questionnaire scores.Measurements and Main Results: A total of 190 subjects (128 EBV and 62 SoC) were randomized. At 12 months, 47.7% EBV and 16.8% SoC subjects had a Delta FEV1 greater than or equal to 15% (P Conclusions: Zephyr EBV provides clinically meaningful benefits in lung function, exercise tolerance, dyspnea, and quality of life out to at least 12 months, with an acceptable safety profile in patients with little or no collateral ventilation in the target lobe.

Published
2018

15. Untargeted LC-MS/MS Profiling of Cell Culture Media Formulations for Evaluation of High Temperature Short Time Treatment Effects

Author

Anna Lindeberg, Simone Albrecht, Nicola McGillicuddy, Christian Kaisermayer, Brian Morrissey, Patrick Floris, and Jonathan Bones

Subjects
0106 biological sciences, Hot Temperature, Time Factors, Chromatography, Chemistry, 010401 analytical chemistry, CHO Cells, Cell culture media, Tandem mass spectrometry, 01 natural sciences, Culture Media, 0104 chemical sciences, Analytical Chemistry, Maillard reaction, symbols.namesake, Cricetulus, Tandem Mass Spectrometry, 010608 biotechnology, Lc ms ms, symbols, Animals, Cells, Cultured, Chromatography, Liquid
Abstract

An untargeted LC-MS/MS platform was implemented for monitoring variations in CHO cell culture media upon exposure to high temperature short time (HTST) treatment, a commonly used viral clearance upstream strategy. Chemically defined (CD) and hydrolysate-supplemented media formulations were not visibly altered by the treatment. The absence of solute precipitation effects during media treatment and very modest shifts in pH values observed indicated sufficient compatibility of the formulations evaluated with the HTST-processing conditions. Unsupervised chemometric analysis of LC-MS/MS data, however, revealed clear separation of HTST-treated samples from untreated counterparts as observed from analysis of principal components and hierarchical clustering sample grouping. An increased presence of Maillard products in HTST-treated formulations contributed to the observed differences which included organic acids, observed particularly in chemically defined formulations, and furans, pyridines, pyrazines, and pyrrolidines which were determined in hydrolysate-supplemented formulations. The presence of Maillard products in media did not affect cell culture performance with similar growth and viability profiles observed for CHO-K1 and CHO-DP12 cells when cultured using both HTST-treated and untreated media formulations.

Published
2017

17. BS15 Multiplexed measurement of protein biomarkers of cardiovascular disease in blood

Author

Brian Morrissey, Christopher A. Watson, Belinda Hernández, Nadezhda Glezeva, Cathy Rooney, Claire Tonry, Mark Ledwidge, Stephen R. Pennington, John A. Baugh, and Kenneth McDonald

Subjects
Oncology, medicine.medical_specialty, Ejection fraction, business.industry, medicine.drug_class, Selected reaction monitoring, Gold standard (test), Disease, medicine.disease, Triple quadrupole mass spectrometer, Internal medicine, Heart failure, medicine, Natriuretic peptide, Biomarker (medicine), business
Abstract

Brief introduction Almost half of all deaths in Europe are attributable to by Cardiovascular Disease (CVD). There is a critical unmet need for better biomarkers so that CVD can be diagnosed at an earlier stage and with greater accuracy. Mass spectrometry-based multiple reaction monitoring (MRM) allows for rapid, targeted measurement of multiple protein biomarkers via detection of ‘proteotypic’ peptide fragments. Such assays can be developed in blood samples, which is desirable for minimally-invasive, routine monitoring of cardiovascular health. The purpose of this study was to design a robust MRM-based assay for the simultaneous detection and measurement of a panel of 36 proteins, including 19 known and 17 novel protein biomarkers of CVD, in blood. The overall aim was to evaluate the potential clinical utility of this biomarker panel for prediction of heart failure in a cohort of 500 patients. Explanation of basic methods Proteotypic peptides for each of the 36 candidate biomarker proteins were identified using Skyline and Spectrum Mill PeptideSelector software. MRM assays were developed using nanoflow reverse phase C18 chromatographic ChipCube based separation, coupled to a 6460 triple quadrupole mass spectrometer. Patient samples and synthetic peptides were used to obtain reference MS/MS spectra for building high quality MRM assays. For initial verification of the candidate protein biomarker panel, the MRM assay was applied, in a sample blinded manner, to a cohort of 500 serum samples from patients with heart failure and age-matched non-heart failure controls with CVD risk-factors. Results MRM assays were established for 35 peptides, corresponding to 9 of the known candidate biomarker proteins and all 16 of the novel biomarkers (Table 1). Individually, a number of the biomarker proteins show differential expression between heart failure with preserved and reduced ejection fraction (Table 2). Combined measurement of all biomarker proteins was found to have greater predictive capacity for heart failure than the current gold standard of B-type natriuretic peptide (BNP) alone. A statistical mode found that the biomarker panel, combined with BNP was capable of correctly predicting heart failure in blinded patient samples with accuracy of 82.19% AUC of 0.89 (Figure 1). Conclusions/Implications Through this study, assays have been developed for robust, multiplexed measurement of 26 CVD biomarker proteins in patient serum samples. Here it was observed that measurement of the full panel of CVD protein biomarkers offers more accurate prediction of heart failure than measurement of BNP alone. This panel will need to be further validated in independent patient cohorts. Conflict of interest None

Published
2019

18. Quantitative Host Cell Protein Analysis Using Two Dimensional Data Independent LC–MSE

Author

Ian W. Marison, Jonathan Bones, Stefan Mittermayr, Amy Farrell, Natalia Navas Iglesias, Niaobh Mc Loughlin, and Brian Morrissey

Subjects
Proteomics, Time Factors, medicine.drug_class, CHO Cells, Buffers, Monoclonal antibody, 01 natural sciences, Mass Spectrometry, Analytical Chemistry, 03 medical and health sciences, Cricetulus, medicine, Animals, Humans, Secretion, 030304 developmental biology, 0303 health sciences, Chromatography, biology, Elution, Chemistry, Chinese hamster ovary cell, 010401 analytical chemistry, Antibodies, Monoclonal, Hydrogen-Ion Concentration, 0104 chemical sciences, biology.protein, Cattle, Antibody, Critical quality attributes, Protein A, Chromatography, Liquid
Abstract

Host cell proteins (HCPs) are bioprocess-related impurities arising from cell-death or secretion from nonhuman cells used for recombinant protein production. Clearance of HCPs through downstream purification (DSP) is required to produce safe and efficacious therapeutic proteins. While traditionally measured using anti-HCP ELISA, more in-depth approaches for HCP characterization may ensure that risks to patients from HCPs are adequately assessed. Mass spectrometry methods provide rationale for targeted removal strategies through the provision of both qualitative and quantitative HCP information. A high pH, low pH, reversed-phase data independent 2D-LC-MS(E) proteomic platform was applied to determine HCP repertoires in the Protein A purified monoclonal antibody (mAb) samples as a function of culture harvest time, elution buffer used for DSP and also following inclusion of additional DSP steps. Critical quality attributes (CQAs) were examined for mAbs purified with different Protein A elution buffers to ensure that the selected buffers not only minimized the HCP profile but also exhibited no adverse effect on product quality. Results indicated that an arginine based Protein A elution buffer minimized the levels of HCPs identified and quantified in a purified mAb sample and also demonstrated no impact on product CQAs. It was also observed that mAbs harvested at later stages of cell culture contained higher concentrations of HCPs but that these were successfully removed by the addition of DSP steps complementary to Protein A purification. Taken together, our results showed how mass spectrometry based methods for HCP determination in conjunction with careful consideration of processing parameters such as harvest time, Protein A elution buffers, and subsequent DSP steps can reduce the HCP repertoire of therapeutic mAbs.

Published
2015

19. Discovery and Longitudinal Evaluation of Candidate Protein Biomarkers for Disease Recurrence in Prostate Cancer

Author

Lisa Staunton, Brian Morrissey, Stephen R. Pennington, John Armstrong, Carmel O'Shea, Claire Tonry, Darren Doherty, Aoife M. Shannon, and Brian Flatley

Subjects
Male, Oncology, medicine.medical_specialty, Protein biomarkers, medicine.medical_treatment, Serum protein, Disease, Biochemistry, Prostate cancer, Tandem Mass Spectrometry, Internal medicine, Biomarkers, Tumor, medicine, Humans, Longitudinal Studies, business.industry, Prostatic Neoplasms, General Chemistry, medicine.disease, Neoplasm Proteins, Radiation therapy, Clinical trial, Hormonal therapy, Neoplasm Recurrence, Local, business, Chromatography, Liquid, Hormone
Abstract

When compared with hormonal therapy alone, treatment with combined hormone and radiation therapy (CHRT) gives improved disease-specific survival outcomes for patients with prostate cancer; however, a significant number of CHRT patients still succumb to recurrent disease. The purpose of this study was to use longitudinal patient samples obtained as part of an ongoing noninterventional clinical trial (ICORG06-15) to identify and evaluate a potential serum protein signature of disease recurrence. Label-free LC-MS/MS based protein discovery was undertaken on depleted serum samples from CHRT patients who showed evidence of disease recurrence (n = 3) and time-matched patient controls (n = 3). A total of 104 proteins showed a significant change between these two groups. Multiple reaction monitoring (MRM) assays were designed for a subset of these proteins as part of a panel of putative prostate cancer biomarkers (41 proteins) for evaluation in longitudinal serum samples. These data revealed significant interpatient variability in individual protein expression between time of diagnosis, disease recurrence, and beyond and serve to highlight the importance of longitudinal patient samples for evaluating the use of candidate protein biomarkers in disease monitoring.

Published
2015

20. Medium-mediated effects increase cell killing in a human keratinocyte cell line exposed to solar-simulated radiation

Author

Alanna Maguire, Brian Morrissey, James E. Walsh, Fiona M. Lyng, Department of Education & Science, and Technological Research Strand I

Subjects
Keratinocytes, medium mediated, Programmed cell death, Cell Survival, Riboflavin, Cell, Biology, Antioxidants, photosensitiser, Cell Line, Phenolsulfonphthalein, Colony-Forming Units Assay, chemistry.chemical_compound, Solar UV, medicine, Humans, Radiology, Nuclear Medicine and imaging, riboflavin, reactive oxygen species, Phenol red, chemistry.chemical_classification, Reactive oxygen species, phenol red, Photosensitizing Agents, Cell Death, Radiological and Ultrasound Technology, digestive, oral, and skin physiology, food and beverages, Culture Media, Cell biology, Cell killing, medicine.anatomical_structure, Biochemistry, chemistry, Spectrophotometry, Cell culture, Toxicity, Sunlight, Reactive Oxygen Species
Abstract

Purpose: The objective of this study is to investigate whether cell culture medium is 40 a biologically relevant exposure medium that can be employed in non-ionising photobiological investigations. 42 Methods: The effect of solar simulated irradiation on cell culture medium and its ability to elicit cell death was studied. The role of reactive oxygen species (ROS), cell 44 secreted factors, and the contribution of individual components of the medium were investigated. 46 Results: Cell death was found to be primarily mediated through the formation of ROS via riboflavin photosensitisation and degradation in the cell culture medium. Phenol 48 red was found to significantly reduce the cell killing ability of riboflavin. Exposures in riboflavin free medium resulted in significantly increased cell survival compared to 50 identical exposures in riboflavin containing medium. Conclusions: This study has shown that solar radiation toxicity is augmented by cell 52 culture medium due to the presence of riboflavin. Results suggest that exposures performed in phenol red free medium may serve to increase phototoxic effects if 54 riboflavin is present. Riboflavin free media is recommended for solar radiation investigations to eliminate concerns regarding riboflavin photosensitisation and nutrient 56 deprivation.

Published
2010

21. Human Proteomics

Author

Brian Morrissey, Lisa Staunton, and Stephen R. Pennington

Published
2014

22. The 'Evolution' of Advertising

Author

High, Brian Morrissey Kamau and Parpis, Eleftheria

Subjects
Cannes Lions International Advertising Festival -- 2007 AD, Spot advertising -- Forecasts and trends -- Achievements and awards, Marketing industry -- Industry forecasts -- Achievements and awards -- Forecasts and trends, Market trend/market analysis, Law
Abstract

Cannes, France 'Evolution' was the watchword at the 2007 Cannes Lions last week, as 11,000 delegates from the ad industry gathered in the South of France to celebrate creativity and [...]

Published
2007

23. Tribal DDB Learns Lesson In Conflicts

Author

Williamson, Brian Morrissey And Richard

Subjects
Tribal DDB Worldwide -- Contracts -- Management -- Advertising, Walmart Inc. -- Contracts -- Advertising -- Management, Advertising agencies -- Contracts -- Management, Discount stores -- Contracts -- Advertising, Company business management, Contract agreement, Law
Abstract

For all the talk of digital as a different ball game, some rules remain the same, particularly the one that says agencies don't work for clients' competitors. While project work [...]

Published
2006

24. Development of a label-free LC-MS/MS strategy to approach the identification of candidate protein biomarkers of disease recurrence in prostate cancer patients in a clinical trial of combined hormone and radiation therapy

Author

Carmel O'Shea, Stephen R. Pennington, Aoife M. Shannon, Brian Morrissey, Lisa Staunton, John Armstrong, Martina Sheehan, and Cathy Rooney

Subjects
Oncology, Male, medicine.medical_specialty, Time Factors, Antineoplastic Agents, Hormonal, medicine.medical_treatment, Clinical Biochemistry, Disease, Bioinformatics, Prostate cancer, Text mining, Recurrence, Tandem Mass Spectrometry, Internal medicine, medicine, Biomarkers, Tumor, Humans, Nanotechnology, Clinical significance, Trypsin, Biomarker discovery, Chromatography, High Pressure Liquid, Principal Component Analysis, business.industry, Prostatic Neoplasms, Blood Proteins, medicine.disease, Combined Modality Therapy, Radiation therapy, Clinical trial, Biomarker (medicine), business
Abstract

Purpose Combined hormone and radiation therapy (CHRT) is one of the principle curative regimes for localised prostate cancer (PCa). Following treatment, many patients subsequently experience disease recurrence however; current diagnostics tests fail to predict the onset of disease recurrence. Biomarkers that address this issue would be of significant advantage. Experimental design Label-free LC-MS/MS for protein biomarker discovery and MRM for targeted confirmation were applied to patient serum samples accrued in a non-interventional clinical trial of CHRT. Results Analysis of time-matched patient samples from a patient with disease recurrence compared with a time match disease-free individual supported the identification of 287 proteins. Of these, 141 proteins were quantified, 95 proteins changed in their expression (P ≤ 0.05 and ≥1.5-fold change) and of these 16 were selected for MRM confirmation. The protein expression changes observed in the label-free LC-MS/MS and MRM analysis were found to be highly correlated (R2 = 0.85). Conclusions and clinical relevance The establishment of a clinical trial to support the acquisition of samples and development of a pipeline for MS-based biomarker discovery and validation should contribute to the identification of a serum protein signature to predict or monitor the outcome of treatment of patients with PCa.

Published
2013

26. CONTRIBUTORS

Author

Cynthia K. Aaron, Jawaid Akhtar, Steven E. Aks, Timothy E. Albertson, Alfred Aleguas, Linda G. Allison, Angela C. Anderson, Juan C. Arias, Alexander B. Baer, Frèdèric J. Baud, Carl R. Baum, Martin Belson, John G. Benitez, Neal L. Benowitz, David P. Betten, Brian Christopher Betts, Lawrence Stilwell Betts, Michael Beuhler, Steven B. Bird, Carolyn M. Blume-Odom, Stephen W. Borron, Edward W. Boyer, Sally M. Bradberry, Jeffrey Brent, D. Eric Brush, Michael J. Burns, Javier R. Caldera, Thomas R. Caraccio, Edward W. Cetaruk, Andrew Chan, Peter B. Chase, James Cisek, Richard F. Clark, Kirk L. Cumpston, Steven C. Curry, Paul I. Dargan, G. Patrick Daubert, João Delgado, Valerie A. Dobiesz, J. Ward Donovan, Robert P. Dowsett, Antonio Dueñas-Laita, Judith M. Eisenberg, Timothy B. Erickson, Michele Burns Ewald, Susan Farrell, Tania M. Fatovich, Miguel C. Fernàndez, J.W. Fijen, Chris Foley, R. Brent Furbee, Ann-Jeannette Geib, Robert J. Geller, Carl A. Germann, Melissa L. Givens, Ronald E. Goans, Nora Goldschlager, Andis Graudins, Michael I. Greenberg, Tee L. Guidotti, Alan H. Hall, Christine A. Haller, Daniel A. Handel, Philippe Hantson, Matthew W. Hedge, Fred M. Henretig, Michael G. Holland, Knut Erik Hovda, Dag Jacobsen, Alison L. Jones, David N. Juurlink, Ziad N. Kazzi, Nicholas J. Kenyon, Fergus Kerr, Daniel C. Keyes, Edwin M. Kilbourne, Richard Kingston, Mark A. Kirk, Laura J. Klein, Kurt C. Kleinschmidt, Wendy Klein-Schwartz, Edward P. Krenzelok, Melisa W. Lai, Frèdèric Lapostolle, Eric J. Lavonas, Michael Levine, William J. Lewander, Ivan E. Liang, Erica L. Liebelt, James G. Linakis, Christopher H. Linden, Richard Lynton, Rebekah C. Mannix, Jack Maypole, R.B. McFee, Charles McKay, Jude McNally, Bruno Mégarbane, J. Meulenbelt, Dana B. Mirkin, Brent W. Morgan, Brian Morrissey, Allison A. Muller, Nancy G. Murphy, Kristine A. Nañagas, Jeffrey B. Nemhauser, Heikki Erik Nikkanen, Kent R. Olson, John D. Osterloh, Wesley Palatnick, Robert B. Palmer, Alberto Perez, Holly E. Perry, Scott D. Phillips, David C. Pigott, Heidi Pinkert, Alex T. Proudfoot, Rouhollah Prueitt, Lawrence S. Quang, James W. Rhee, William H. Richardson, Jon C. Rittenberger, Steven D. Salhanick, Anthony J. Scalzo, Heather K. Schuller, Michael D. Schwartz, Donna Seger, Michael W. Shannon, Mahesh Shrestha, Leo J. Sioris, Marco L. Sivilotti, Sara Skarbek-Borowska, Susan C. Smolinske, Curtis P. Snook, David G. Spoerke, Jeffrey R. Suchard, Young-Jin Sue, Matthew D. Sztajnkrycer, Sharon Ternullo, Dung Thai, R. Steven Tharratt, Jerry D. Thomas, Karen E. Thomas, Josef G. Thundiyil, Anthony J. Tomassoni, Stephen J. Traub, John Harris Trestrail III, J. Allister Vale, Jason Vena, Frank G. Walter, Richard Y. Wang, Sharita E. Warfield, Paul M. Wax, Suzanne R. White, James F. Wiley, Saralyn R. Williams, Alan David Woolf, Mark Yarema, and Luke Yip

Published
2007

28. MSN extends overture deal

Author

Brian Morrissey

Subjects
Microsoft Corp. -- Contracts, Microsoft Corp. -- Alliances and partnerships, Overture Services Inc. -- Contracts, Overture Services Inc. -- Alliances and partnerships, Computer software industry -- Contracts, Computer software industry -- Alliances and partnerships, Online services -- Contracts, Online services -- Alliances and partnerships, Contract agreement, Cable television/data services, Online services, Business, Construction and materials industries
Published
2003

29. E-mailers weigh impact of challenge-response

Author

Brian Morrissey

Subjects
Spam (Junk email) -- Product information, Email marketing -- Aims and objectives, Unsolicited bulk e-mail, Business, Construction and materials industries
Published
2003

30. Anti-spam bill is a compromise for DMers

Author

Brian Morrissey

Subjects
Spam (Junk email) -- Laws, regulations and rules, Unsolicited bulk e-mail, Government regulation, Business, Construction and materials industries, Direct Marketing Association -- Beliefs, opinions and attitudes
Published
2003

31. Autonomy

Author

Hugh Black and Brian Morrissey

Subjects
Pulmonary and Respiratory Medicine, Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine
Published
2011

33. Lycos dumps overture for Google

Author

Brian Morrissey

Subjects
Lycos Inc. -- Mergers, acquisitions and divestments, Lycos Inc. -- Cases, Overture Networks Inc. -- Mergers, acquisitions and divestments, Yahoo! Inc. -- Mergers, acquisitions and divestments, Web browsers -- Analysis, Computer services industry -- Mergers, acquisitions and divestments, Information services industry, Information services industry, Web browser, Computer services industry, Company acquisition/merger, Company legal issue, Business, Construction and materials industries
Published
2003

35. EU opt-in E-mail directive takes effect

Author

Brian Morrissey

Subjects
Silverpop Systems Inc. -- Aims and objectives, Spam (Junk email) -- Laws, regulations and rules, Computer software industry -- Aims and objectives, Email marketing -- Laws, regulations and rules, Electronic mail systems -- Advertising, Unsolicited bulk e-mail, E-mail, Government regulation, Business, Construction and materials industries, European Union -- Laws, regulations and rules
Published
2003

36. Newspapers report online ad sales rise in Q3

Author

Brian Morrissey

Subjects
Newspapers -- Target marketing, Internet/Web advertising -- Aims and objectives, Internet/Web advertising -- Growth, Company growth, Internet/Web advertising, Business, Construction and materials industries
Published
2003

37. Yahoo reinforces its spam defenses

Author

Brian Morrissey

Subjects
Yahoo! Inc. -- Product information, Online services -- Product information, Information services -- Product information, Online information services -- Product information, Spam (Junk email), Unsolicited bulk e-mail, Online information service, Business, Construction and materials industries
Published
2003

38. With no dma spam definition, internet groups step in

Author

Brian Morrissey

Subjects
Spam (Junk email) -- Analysis, Unsolicited bulk e-mail, Business, Construction and materials industries, Direct Marketing Association -- Aims and objectives
Published
2003

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