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58. Enhancement of Sensor Data Transmission by Inference and Efficient Data Processing

Author

Kang, James Jin, Luan, Tom H., Larkin, Henry, Diniz Junqueira Barbosa, Simone, Series editor, Chen, Phoebe, Series editor, Du, Xiaoyong, Series editor, Filipe, Joaquim, Series editor, Kara, Orhun, Series editor, Kotenko, Igor, Series editor, Liu, Ting, Series editor, Sivalingam, Krishna M., Series editor, Washio, Takashi, Series editor, Batten, Lynn, editor, and Li, Gang, editor

Published
2016
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61. Can Targeting Sphincter Spasm Reduce Post-Haemorrhoidectomy Pain? A Systematic Review and Meta-Analysis

Author

James Jin, Hanson Unasa, Praharsh Bahl, Melbourne Mauiliu-Wallis, Darren Svirskis, and Andrew Hill

Subjects
Surgery
Abstract

Background Haemorrhoidectomy is often complicated by significant post-operative pain, to which spasm of the internal anal sphincter is thought to be a contributing factor. This study appraises the evidence behind interventions aimed at lowering sphincter spasm to relieve post-haemorrhoidectomy pain. Methods A Preferred Reporting Items for Systematic Reviews and Meta-analyses compliant systematic review was conducted. Medline, EMBASE, and CENTRAL databases were systematically searched. All RCTs which compared interventions targeting the internal anal sphincter to relieve pain post excisional haemorrhoidectomy were included. The primary outcome measure was pain on the visual analogue scale. Results Of the initial 10,221 search results, 39 articles were included in a qualitative synthesis, and 33 studies were included in a meta-analysis. Topical glyceryl trinitrate (GTN) reduced pain on day 7 (7 studies, 485 participants), with a mean difference and 95% confidence interval (MD, 95% CI) of −1.34 (−2.31; −0.37), I2 = 91%. Diltiazem reduced pain on day 3 on the VAS, and the MD was −2.75 (−398; −1.51) shown in five studies (n = 227). Botulinum toxin reduced pain on day 7, in four studies with 178 participants, MD −1.43 (−2.50; −0.35) I2 = 62%. The addition of Lateral Internal Sphincterotomy to haemorrhoidectomy reduced pain on day 2 in three studies with 275 participants, MD of −2.13 (−3.49; −0.77) I2 = 92%. The results were limited by high heterogeneity and risk of bias. Conclusion Evidence suggests that lateral sphincterotomy, administration of botulinum toxin and the application of topical diltiazem or GTN can reduce post-operative pain after haemorrhoidectomy. Lateral sphincterotomy should not be routinely used due to the risk of incontinence.

Published
2022
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67. A comprehensive review on machine learning in healthcare industry: Classification, restrictions, opportunities and challenges

Author

An, Qi, Rahman, Saifur, Zhou, Jingwen, Kang, James Jin, An, Qi, Rahman, Saifur, Zhou, Jingwen, and Kang, James Jin

Abstract

Recently, various sophisticated methods, including machine learning and artificial intelligence, have been employed to examine health-related data. Medical professionals are acquiring enhanced diagnostic and treatment abilities by utilizing machine learning applications in the healthcare domain. Medical data have been used by many researchers to detect diseases and identify patterns. In the current literature, there are very few studies that address machine learning algorithms to improve healthcare data accuracy and efficiency. We examined the effectiveness of machine learning algorithms in improving time series healthcare metrics for heart rate data transmission (accuracy and efficiency). In this paper, we reviewed several machine learning algorithms in healthcare applications. After a comprehensive overview and investigation of supervised and unsupervised machine learning algorithms, we also demonstrated time series tasks based on past values (along with reviewing their feasibility for both small and large datasets).

Published
2023

68. DoS/DDoS-MQTT-IoT: A dataset for evaluating intrusions in IoT networks using the MQTT protocol

Author

Alatram, Alaa, Sikos, Leslie F., Johnstone, Mike, Szewczyk, Patryk, Kang, James Jin, Alatram, Alaa, Sikos, Leslie F., Johnstone, Mike, Szewczyk, Patryk, and Kang, James Jin

Abstract

Adversaries may exploit a range of vulnerabilities in Internet of Things (IoT) environments. These vulnerabilities are typically exploited to carry out attacks, such as denial-of-service (DoS) attacks, either against the IoT devices themselves, or using the devices to perform the attacks. These attacks are often successful due to the nature of the protocols used in the IoT. One popular protocol used for machine-to-machine IoT communications is the Message Queueing Telemetry Protocol (MQTT). Countermeasures for attacks against MQTT include testing defenses with existing datasets. However, there is a lack of real-world test datasets in this area. For this reason, this paper introduces a DoS/DDoS-MQTT-IoT dataset—that contains various DoS/DDoS attack scenarios using MQTT traffic—to help develop and test countermeasures against such attacks. To this end, a physical IoT testbed was constructed and a large volume of IoT data was generated that included standard MQTT traffic as well as 10 DoS scenarios. The usability of the dataset has been evaluated via machine learning.

Published
2023

69. Nafion modified titanium nitride pH sensor for future biomedical applications

Author

Shylendra, Shimrith Paul, Wajrak, Magdalena, Alameh, Kamal, Kang, James Jin, Shylendra, Shimrith Paul, Wajrak, Magdalena, Alameh, Kamal, and Kang, James Jin

Abstract

pH sensors are increasingly being utilized in the biomedical field and have been implicated in health applications that aim to improve the monitoring and treatment of patients. In this work, a previously developed Titanium Nitride (TiN) solid-state pH sensor is further enhanced, with the potential to be used for pH regulation inside the human body and for other biomedical, industrial, and environmental applications. One of the main limitations of existing solid-state pH sensors is their reduced performance in high redox mediums. The potential shift E0 value of the previously developed TiN pH electrode in the presence of oxidizing or reducing agents is 30 mV. To minimize this redox shift, a Nafion-modified TiN electrode was developed, tested, and evaluated in various mediums. The Nafion-modified electrode has been shown to shift the E0 value by only 2 mV, providing increased accuracy in highly redox samples while maintaining acceptable reaction times. Overcoming the redox interference for pH measurement enables several advantages of the Nafion-modified TiN electrode over the standard pH glass electrode, implicating its use in medical diagnosis, real-time health monitoring, and further development of miniaturized smart sensors.

Published
2023

73. Ultrafine Flexible Endoscope Visualization to Assist in the Removal of a Huge Spinal Extradural Arachnoid Cyst: Case Report and Literature Review

Author

Peihai Zhang, Huiting Liu, Zhenxin Sun, Yi Guo, Guihuai Wang, and James Jin Wang

Subjects
Arachnoid Cysts, Endoscopes, Humans, Surgery, Neurology (clinical), Magnetic Resonance Imaging, Spinal Cord Diseases, Spine
Abstract

Arachnoid cysts are one of the benign spinal cystic lesions. Multiple nerve roots and spinal cord may be compressed by it, and operating is often recommended. Traditional surgical procedures often choose the posterior median approach, separating the paravertebral muscles, milling the lamina, fully exposing the cyst, partially or completely removing the cyst wall, looking for the leak, and then suturing and sealing. Here we present a case of giant spinal extradural arachnoid cyst in which a ultrafine flexible endoscope was used to visualize cystic spaces and identity the leaks. We repaired the leak after removing part of the cyst wall under the operating microscope, and the patient had an excellent recovery.

Published
2022
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74. Spinal Angiolipomas : Clinical Characteristics, Surgical Strategies and Prognosis

Author

Zhang, Xiaolei, Dong, Sheng, Wang, Guoqin, Zhang, Huifang, Wang, James Jin, and Wang, Guihuai

Subjects
Dorsum, Retrospective review, medicine.medical_specialty, Clinical Article, business.industry, General Neuroscience, Subtotal Resection, Prognosis, Trunk, Spine, Surgery, medicine.anatomical_structure, Diagnosis, medicine, Angiolipoma, spine, Neurology (clinical), Good prognosis, Surgical treatment, Intervertebral foramen, business, Subcutaneous tissue
Abstract

Objective : Angiolipomas are usually found in the subcutaneous tissue of the trunk and limbs. Spinal angiolipomas (SALs) are uncommon and have rarely been reported. We report a series of nine SALs patients who received surgical treatment in our department. To summarize the clinical characteristics of SALs, propose our surgical strategies, and evaluate the effects of the operation.Methods : This was a retrospective review of nine SALs patients who received surgical treatment from August 2015 to March 2020. Total or subtotal resection was determined by the axial localization (dorsal or ventral) and the extent of intervertebral foramen involvement. The outcomes were assessed based on the modified Japanese Orthopaedic Association (mJOA) scoring system utilized before surgery and at various follow-up points.Results : Among the nine patients, the mean mJOA score before surgery was 6.6±2.3, compared with 10.1±1.1 at the last follow-up time point (33.4±11.8 months). All patients achieved good outcomes, even in cases of subtotal resection.Conclusion : Early surgical resection of SALs is recommended, and the specific procedures should be determined by the axial localization (dorsal or ventral) and the extent of intervertebral foramen involvement. Most of the patients had a good prognosis, even in cases of subtotal resection.

Published
2022
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76. Thromboembolic and bleeding risks in edoxaban patients with pacemaker and cardiac monitoring procedures: Outcomes of the Global EMIT program

Author

Thomas Vanassche, Paolo Colonna, Martin Unverdorben, Cathy Chen, Manish Saxena, Amparao Santamaria, James Jin, R G Wilkins, and Christian von Heymann

Subjects
Male, Pacemaker, Artificial, medicine.medical_specialty, Pyridines, medicine.medical_treatment, Population, Taiwan, Hemorrhage, chemistry.chemical_compound, Ischemia, Risk Factors, Edoxaban, Thromboembolism, Republic of Korea, Humans, Medicine, Cardiac Resynchronization Therapy Devices, Prospective Studies, education, Aged, education.field_of_study, business.industry, Incidence (epidemiology), Anticoagulants, Atrial fibrillation, General Medicine, Perioperative, medicine.disease, Thrombosis, Europe, Thiazoles, chemistry, Emergency medicine, Female, Cardiac monitoring, Cardiology and Cardiovascular Medicine, business, Complication, Factor Xa Inhibitors
Abstract

Introduction Limited data were published on the management of direct oral anticoagulants in the insertion of pacemaker and cardiac monitoring devices. This study describes the management and outcomes of edoxaban, a direct oral factor Xa inhibitor, in patients undergoing pacemaker or monitoring device implantation in routine clinical practice. Methods and results EMIT-AF/VTE collected data of patients from Europe, Korea, and Taiwan. Timing and duration of peri-procedural interruption of edoxaban were at the treating physician's discretion. Pacemakers or monitoring devices were implanted into 136 patients who were evaluated from five days pre- until 30 days post-procedure. The primary outcomes were the incidences of acute thromboembolic events (ATE), ischemic events, and International Society on Thrombosis and Haemostasis defined Major Bleeding; secondary outcomes included incidence of Clinically Relevant Non-Major Bleeding (CRNMB) and perioperative edoxaban interruption times. Conformance with European Heart Rhythm Association (EHRA) Guidance on interruption of DOAC therapy was variable: of the cardiac monitoring device patients, where no interruption of therapy would be expected, nonetheless, 62.5% had interruption of treatment, whereas in pacemaker procedures, where interruption would be expected, 23.4% had no interruption. No ATE or ischemic events occurred. One case of CRNMB and two of minor bleeding occurred. All bleedings occurred more than three days after the procedure. Conclusion/relevance The periprocedural complication risk for edoxaban treated patients undergoing pacemaker or invasive cardiac monitoring implantation was low. This population of patients was well managed in routine practice. This article is protected by copyright. All rights reserved.

Published
2021
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77. Icosapent Ethyl Reduces Ischemic Events in Patients With a History of Previous Coronary Artery Bypass Grafting: REDUCE-IT CABG

Author

Subodh Verma, Deepak L. Bhatt, Ph. Gabriel Steg, Michael Miller, Eliot A. Brinton, Terry A. Jacobson, Nitish K. Dhingra, Steven B. Ketchum, Rebecca A. Juliano, Lixia Jiao, Ralph T. Doyle, Craig Granowitz, C. Michael Gibson, Duane Pinto, Robert P. Giugliano, Matthew J. Budoff, R. Preston Mason, Jean-Claude Tardif, Christie M. Ballantyne, Fabrice M.A.C. Martens, Astrid Schut, Brian Olshansky, Mina Chung, Al Hallstrom, Lesly Pearce, Cyrus Mehta, Rajat Mukherjee, Anjan K. Chakrabarti, Eli V. Gelfand, Megan Carroll Leary, Duane S. Pinto, Yuri B. Pride, Steven Ketchum, Ramakrishna Bhavanthula, Gertrude Chester, Christina Copland, Katelyn Diffin, Ralph Doyle, Kurt Erz, Alex Giaquinto, Paula Glanton, Angela Granger, Richard H. Iroudayassamy, Rebecca Juliano, James Jin, Dimitry Klevak, Hardik Panchal, Robert Wang, Shin-Ru Wang, Gerard Abate, Peggy J. Berry, Rene Braeckman, Declan Doogan, Anne Elson, Amy HauptmannBaker, Isabel Lamela, Catherine Lubeck, Mehar Manku, Sabina Murphy, Monica Sanford, William Stirtan, Paresh Soni, Arnaud Bastien, Demetria Foster, Evangelito Gascon, Judith Johnson, Lasbert Latona, Gang Liu, Sandra Palleja, Nelly Sanjuan, Jimmy Shi, William Stager, Mukund Venkatakrishnan, Ahmed Youssef-Agha, Julie Zhu, Leela Aertker, Suresh Ankolekar, Lisa Goldberg, Natasa Rajicic, Jianfen Shu, Heng Zou, Magdy Mikhail, Gamil Dawood, N. Mathew Koshy, Sandip K. Mukherjee, Rafik Abadier, Andrea L. Lawless, William P. McGuinn, Howard Weintraub, Kathryn Rohr, Edmund Claxton, Robert J. Weiss, Terry D. Klein, Mani Nallasivan, Stephen Crowley, Marilyn King, Anthony D. Alfieri, David Fitz-Patrick, Irving Loh, Nolan J. Mayer, Rakesh Prashad, Samuel Lederman, Debra Weinstein, Harold E. Bays, Keith Chu, Alireza Maghsoudi, Paul D. Thompson, Jeff Carstens, Anna Chang, Kenneth R. Cohen, Julius Dean, Howard S. Ellison, Bernard Erickson, Enrique A. Flores, Daniel W. Gottlieb, Paul Grena, John R. Guyton, Peter H. Jones, John M. Joseph, Norman E. Lepor, Sam Lerman, Robert D. Matheney, Theodore R. Pacheco, Michael B. Russo, John Rubino, Edward S. Pereira, Albert A. Seals, Eduardo Viera, Alan D. Steljes, Jason Thompson, Shaival Kapadia, Michael McIvor, Jorge E. Salazar, Jose O. Santiago, Ralph Vicari, Martin R. Berk, William A. Kaye, Marcus McKenzie, David Podlecki, Brian D. Snyder, Stephen Nash, David M. Herrington, Wallace Johnson, Joseph R. Lee, Ronald Blonder, Alpa M. Patel, Ramon Castello, Susan Greco, Dean J. Kereiakes, Venkatesh K. Nadar, Mark Nathan, Ranganatha P. Potu, Robert Sangrigoli, Richard Smalling, Mitchell Davis, Robert Braastad, James McCriskin, Kunal Bodiwala, Joe L. Hargrove, Mark W. Graves, George Emlein, Raegan W. Durant, James W. Clower, Rohit Arora, Narendra Singh, Lisa Warsinger Martin, W Herbert Haught, Marc P. Litt, Michael D. Klein, Peter Hoagland, Michael Goldstein, Marco S. Mazzella, Daniel H. Dunker, Brian H. Kahn, Carlos S. Ince, Frank A. McGrew, Jay Lee, David Pan, Salman A. Khan, Uri Elkayam, Wasim Deeb, Anne C. Goldberg, Christopher S. Brown, Wayne N. Leimbach, Thomas S. Backer, David R. Sutton, Joel Gellman, Anu R. George, Alan S. Hoffman, Mark Kates, Kishlay Anand, Robert Bear, Brendan J. Cavanaugh, Ramon G. Reyes, Rodolfo Sotolongo, Kenneth Sabatino, Kevin Gallagher, Ehab Sorial, Chris Geohas, Kathleen E. Magness, Bernard P. Grunstra, Frederik A. Martin, William S. Knapp, Mel E. Lucas, John J. Champlin, Jason Demattia, Patrick H. Peters, Judith Kirstein, William J. Randall, Cezar S. Staniloae, Jennifer G. Robinson, Alexander Adler, Christopher Case, Andrew J. Kaplan, Gregory F. Lakin, Krishan K. Goyle, Michael J. DiGiovanna, Chester L. Fisher, Michael Lillestol, Michael Robinson, Robert G. Perry, Lawrence S. Levinson, Brian G. Everhart, Robert D. Madder, Earl F. Martin, Earl E. Martin, Imtiaz Alam, Jose Mari L. Elacion, Robina Poonawala, Taddese T. Desta, Jerome A. Robinson, Gilbert J. Martinez, Jakkidi S. Reddy, Jeffrey D. Wayne, Samuel Mujica Trenche, Westbrook I. Kaplan, Rubin H. Saavedra, Michael D. DiGregorio, Barry D. Bertolet, Neil J. Fraser, Terence T. Hart, Ronald J. Graf, David A. Jasper, Michael Dunn, Dan A. Streja, David J. Strobl, Nan Jiang, Vicki Kalen, Richard Mascolo, Mercedes B. Samson, Michael Stephens, Bret M. Bellard, Mario Juarez, Patrick J. McCarthy, John B. Checton, Michael Stillabower, Edward Goldenberg, Amin H. Karim, Naseem Jaffrani, Robert C. Touchon, Erich R. Fruehling, Clayton J. Friesen, Pradipta Chaudhuri, Frank H. Morris, Robert E. Broker, Rajesh J. Patel, Susan Hole, Randall P. Miller, Francisco G. Miranda, Sadia Dar, Shawn N. Gentry, Paul Hermany, Charles B. Treasure, Miguel E. Trevino, Raimundo Acosta, Anthony Japour, Samuel J. Durr, Thomas Wang, Om P. Ganda, Perry Krichmar, James L. Arter, Douglas Jacoby, Michael A. Schwartz, Amer Al-Karadsheh, Nelson E. Gencheff, John A. Pasquini, Richard Dunbar, Sarah Kohnstamm, Hector F. Lozano, Francine K. Welty, Thomas L. Pitts, Brian Zehnder, Salah El Hafi, Mark A. King, Arnold Ghitis, Marwan M. Bahu, Hooman Ranjbaran Jahromi, Ronald P. Caputo, Robert S. Busch, Michael D. Shapiro, Suhail Zavaro, Munib Daudjee, Shahram Jacobs, Vipul B. Shah, Frank Rubalcava, Mohsin T. Alhaddad, Henry Lui, Raj T. Rajan, Fadi E. Saba, Mahendra Pai N Gunapooti, Tshiswaka B. Kayembe, Timothy Jennings, Robert A. Strzinek, Michael H. Shanik, Pradeep K. Singh, Alastair C. Kennedy, Howard Rubenstein, Ramin Manshadi, Joanne Ladner, Lily Kakish, Ashley Kakish, Amy L. Little, Jaime Gerber, Nancy J. Hinchion, Janet Guarino, Denise Raychok, Susan Budzinski, Kathleen Kelley-Garvin, April Beckord, Jessica Schlinder, Arthur Schwartzbard, Stanley Cobos, Deborah Freeman, David Abisalih, Dervilla McCann, Kylie Guy, Jennifer Chase, Stacey Samuelson, Madeline Cassidy, Marissa Tardif, Jaime Smith, Brenna Sprout, Nanette Riedeman, Julie Goza, Lori Johnson, Chad Kraske, Sheila Hastings, Chris Dutka, Stephanie Smith, Toni McCabe, Kathleen Maloney, Paul Alfieri, Vinay Hosemane, Chanhsamone Syravanh, Cindy Pau, April Limcoiloc, Tabitha Carreira, Taryn S. Kurosawa, Razmig Krumian, Krista Preston, Ashraf Nashed, Daria Schneidman-Fernandez, Jack Patterson, John Tsakonas, Jennifer Esaki, Lynn Sprafka, Porous Patel, Brian Mitchell, Erin M. Ross, Donna Miller, Akash Prashad, Kristina M. Feyler, Natasha Juarbe, Sandra Herrera, Sarah M. Keiran, Becky Whitehead, Whitney Asher, Coury Hobbs, Abbey Elie, Jean Brooks, Amanda L. Zaleski, Brenda Foxen, Barb Lapke, Philippa Wright, Bristol Pavol, Gwen Carangi, Marla Turner, Katharine W. Sanders, Rikita S. Delamar, Virginia L. Wilson, Sarah M. Harvel, Alison M. Cartledge, Kaitlyn R. Bailey, Kathleen Mahon, Timothy Schuchard, Jen Humbert, Mark C. Hanson, Michael P. Cecil, James S. Abraham, Lorie Benedict, Claudia Slayton, Curtis S. Burnett, Rachel W. Ono-Lim, Sharon Budzinski, Shubi A. Khan, Sharon Goss, Terry Techmanski, Farida Valliani, Rimla Joseph, Edith Flores, Laurn Contreras, Ana Aguillon, Carrie-Ann Silvia, Maria Martin, Edmund K. Kerut, Leslie W. Levenson, Louis B. Glade, Brian J. Cospolich, Maureen W. Stein, Stephen P. LaGuardia, Thelma L. Sonza, Tracy M. Fife, Melissa Forschler, Jasmyne Watts, Judy Fritsch, Emese Futchko, Sarah Utech, Scott B. Baker, Miguel F. Roura, Scott A. Segel, James S. Magee, Cathy Jackson, Rebecca F. Goldfaden, Liudmila Quas, Elizabeth C. Ortiz, Michael Simpson, Robert Foster, Christopher Brian, James Trimm, Michael Bailey, Brian Snoddy, Van Reeder, Rachel Wilkinson, Harold Settle, Cynthia Massey, Angela Maiola, Michele Hall, Shelly Hall, Wanda Hall, Mark Xenakis, Janet Barrett, Giovanni Campanile, David Anthou, Susan F. Neill, Steven Karas, Enrique Polanco, Norberto Schechtman, Grace Tischner, Kay Warren, Cynthia St Cyr, Menna Kuczinski, Latrina Alexander, Maricruz Ibarra, Barry S. Horowitz, Jaime Steinsapir, Jeanette Mangual-Coughlin, Brittany Mooney, Precilia Vasquez, Kathleen Rodkey, Alexandria Biberstein, Christine Ignacio, Irina Robinson, Marcia Hibberd, Lisa B. Hoffman, Daniel J. Murak, Raghupathy Varavenkataraman, Theresa M. Ohlson Elliott, Linda A. Cunningham, Heather L. Palmerton, Sheri Poole, Jeannine Moore, Helene Wallace, Ted Chandler, Robert Riley, Farah Dawood, Amir Azeem, Michael Cammarata, Ashleigh Owen, Shivani Aggarwal, Waqas Qureshi, Mohamed Almahmoud, Abdullahi Oseni, Adam Leigh, Erin Barnes, Adam Pflum, Amer Aladin, Karen Blinson, Vickie Wayne, Lynda Doomy, Michele Wall, Valerie Bitterman, Cindi Young, Rachel Grice, Lioubov Poliakova, Jorge Davalos, David Rosenbaum, Mark Boulware, Heather Mazzola, J. Russell Strader, Russell Linsky, David Schwartz, Elizabeth Graf, Alicia Gneiting, Melissa Palmblad, Ashley Donlin, Emily Ensminger, Hillary Garcia, Dawn Robinson, Carolyn Tran, Jeffrey Jacqmein, Darlene Bartilucci, Michael Koren, Barbara Maluchnik, Melissa Parks, Jennifer Miller, Cynthia DeFosse, Albert B. Knouse, Amy Delancey, Stephanie Chin, Thomas Stephens, Mag Sohal, Juana Ingram, Swarooparani Kumar, Heather Foley, Nina Smith, Vera McKinney, Linda Schwarz, Judith Moore, Hildreth Vernon Anderson, Stefano Sdringola-Maranga, Ali Denktas, Elizabeth Turrentine, Rhonda Patterson, John Marshall, Terri Tolar, Donna Patrick, Pamela Schwartzkopf, Anthony M. Fletcher, Frances R. Harris, Sherry Clements, Tiffany Brown, William Smith, Stacey J. Baehl, Robin Fluty, Daniel VanHamersveld, Dennis Breen, Nancy Bender, Beverly Stafford, Tamika Washington, Margaret N. Pike, Mark A. Stich, Evyan Jawad, Amin Nadeem, Jill Nyland, Rhonda Hamer, Kendra Calhoun, Charlotte Mall, Samuel Cadogan, Kati Raynes, Richard Katz, Lorraine Marshall, Rashida Abbas, Jay L. Dinerman, John T. Hartley, Beth Lamb, Lisa Eskridge, Donna Raymond, Kristy Clemmer, Denise M. Fine, Paula Beardsley, Janet Werner, Bette Mahan, Courtney VanTol, Robert Herman, Christine Raiser-Vignola, Felicia McShan, Stefanie A. Neill, David R. Blick, Michael J. Liston, Denetta K. Nelson, Sandra K. Dorrell, Patricia Wyman, Ambereen Quraishi, Fernando Ferro, Frank Morris, Vicki J. Coombs, Autumn M. Mains, Austin A. Campbell, Jeanne Phelps, Cheryl A. Geary, Ellen G. Sheridan, Jean M. Downing, Arie Swatkowski, Tish Redden, Brian Dragutsky, Susan Thomas, Candace Mitchell, Diana Barker, Elanie Turcotte, Deborah Segerson, Jill Guy, Karena De La Mora, Jennifer Hong, Dennis Do, Rose Norris, Faisal Khan, Hector Montero, Stacy Kelly-White, Alan Cleland, Rosalyn Alcalde-Crawford, Melissa Morgan, Brijmohan Sarabu, Megan Minor, Shweta Kamat, Stephanie M. Estes, Nancee Harless, Alicia Disney, Jodi L. Pagano, Chad M. Alford, Noel W. Bedwell, Warren D. Hardy, Kevin DeAndrade, Jessica G. Elmore, Eric Auerbach, Anthony W. Haney, Miriam H. Brooks, Jose Torres, Lois Roper, Terry Backer, Katie Backer, John G. Evans, Ricardo A. Silva, Lorraine H. Dajani, Veronica Yousif, Tammy Ross, Sion K. Roy, Ronald Oudiz, Sajad Hamal, Ferdinand Flores, Amor Leahy, Debra Ayer, Swapna George, Chrisi Carine Stewart, Elvira Orellana, Cristina Boccalandro, Mary Rangel, Suzanne Hennings, Carl Vanselow, Teri Victor, Darlene Birdwell, Paul Haas, Anthony Sandoval, Gina Ciavarella, Caroline Saglam, Amy Bird, Keith Beck, Brian Poliquin, David Dominguez, Brittany Tenorio, Harvonya Perkins, Esther San Roman, Paris Bransford, Christy Lowrance, Marcy Broussard, Mary Ellis, Bobbi Skiles, Jessica Hamilton, Kathryn Hall, Diego Olvera, Julee A. Hartwell, Nevien Sorial, Mary Rickman, Kevin Berman, Nirav Mehta, Annie Laborin, Rodger Rothenberger, Sarah Beauvilliers, Kathy Morrell, Michael P. Schachter, Cindy L. Perkins, Elizabeth A. Gordon, Jennifer Lauer, Kim Bichsel, Kelly Oliver, Leslie J. Mellor, Candice Demattia, Jennifer Schomburg, Yenniffer Moreno, Eduardo Mansur-Garza, Lena Rippstein, Lorie Chacon, Andrea Pena, Michelle King, Susan Richardson, Annette Jessop, Nicole Tucker, Whitney Royer, Gilbert Templeton, Ann Moell, Christine Weller, Melissa J. Botts, Gretel Hollon, Elsa Homberg-Pinassi, Paula Forest, Aref Bin Abhulhak, Devona Chun-Furlong, Deborah Harrington, Emily Harlynn, Marjorie Schmitt, Constance Shelsky, Patricia Feldick, Mary Cherrico, Courtney Jagle, Nicholas Warnecke, Debra Myer, Deanna J. Ruder, Albina Underwood, Alan Rauba, George Carr, Barbara Oberhaus, Jessica Vanderfeltz, Mary Jo Stucky-Heil, Dale R. Gibson, Vonnie Fuentes, Kimberly L. Talbot, William C. Simon, Katlyn J. Grimes, Christina R. Wheeler, Cassaundra Shultz, Rhonda A. Metcalf, Jennifer L. Hill, Michelle R. Oliver, Basharat Ahmad, Fouzal Azeem, Abdul Rahim, George H. Freeman, Dawn Bloch, Heather Freeman, Jamie Brown, Sarah Rosbach, Pamela Melander, Nick Taralson, Alex Liu, Katlyn Harms, Mahfouz Michale, Jose Lopez, Maria Revoredo, Shari Edevane, Sarah Shawley, Timothy L. Jackson, Michael J. Oliver, Dina DeSalle, Patricia J. Matlock, Ionna M. Beraun, Heather Hendrix, Garrett Bromley, Ashley Niemerski, Gabby Teran, Sonia Guerrero, Murtaza Marvi, Zehra Palanpurwala, Andrea Torres, Patty Gloyd, Michelle Conger, Aziz Laurent, Olia Nayor, Catalina S. Villanueva, Munira Khambati, Tabetha J. Mumford, Melanie J. Castillo, Taddese Desta, Jerome Robinson, La Shawn Woods, Anita Bahri, Nancy Herrera, Cecilia Casaclang, Jeffrey R. Unger, Geraldine Martinez, Mia K. Moon, Stephen M. Mohaupt, Larry Sandoval, Louisito Valenzuela, Victora Ramirez, Nelly Mata, Veronica Avila, Marisol Patino, Cynthia Montano-Pereira, Omar Barnett, William M. Webster, Lorraine M. Christensen, Leighna Bofman, Melanie Livingston, Stacey Adams, Joseph Hobbs, Leesa Koskela, Mia Katz, Samuel Mujica-Trenche, Franklin Cala, Noreen T. Rana, Jennifer Scarlett, Milagros Cala Anaya, Marsha R. Jones, Kelly D. Hollis, Debbie Roth, Kristin Eads, Tina Watts, Judy Perkins, Alice Arnold, Daniel C. Ginsberg, Denise Quinn, Nicole Cureton, David B. Fittingoff, Mohammed I. Iqbal, Stephen R. White, Edith Sisneros, Michelle Ducca, David Streja, Danny Campos, Jennifer L. Boak, Farzeen Amir, Felice Anderson, James J. Kmetzo, Mary O. Bongarzone, Dawn Scott, Mary Grace De Leon, Cynthia Buda, William Graettinger, Michelle Alex, Erika Hess, James Govoni, Melissa Bartel, Travis L. Monchamp, Julie S. Roach, Sara Gibson, Amy M. Allfrey, Kristen Timpy, Kathy Bott, Karin A. Soucy, Jean Willis, Cecilia A. Valerio, Anusha Chunduri, Rebecca Coker, Nicole Vidrine, Ellen A. Thompson, Mark A. Studeny, Melissa K. Marcum, Tammy S. Monway, Douglas L. Kosmicki, Melissa J. Kelley, Corey M. Godfrey, Susan L. Krenk, Randy R. Holcomb, Deb K. Baehr, Mary K. Trauernicht, David Rowland Lowry, Betty Bondy Herts, Jeanne E Phelps, Jean-Marie Downing, Carol Gamer Dignon, Elisabeth S. Cockrill, Pravinchandra G. Chapla, Diane Fera, Margaret Chang, Patricia Fredette, Tamie Ashby, Renee Bergin, Zebediah A. Stearns, David B. Ware, Rachael M. Boudreaux, Joanna Rodriguez, Robert McKenzie, Amanda Huber, Rebecca Sommers, Heather Rowe, Stacy McLallen, Michale Haynes, Ashley Adamson, Janice Henderson, Lori McClure, Beverly A. Harris, Laura Ference, Sue Meissner-Dengler, Lisa Treasure, Doreen Nicely, Timothy L. Light, Tracey A. Osborn, Kimberly J. Mai, Pablo Vivas, Jose Rios, Dunia Rodriguez, Roger DeRaad, James Walder, Oscar Bailon, Denice Hockett, Debbie Anderson, Kelli McIntosh, Amber Odegard, Andrew Shepherd, Mary Seifert, Laurence Kelley, Rajendra Shetty, Michael Castine, David Brill, Gregory Fisher, Nicole Richmond, Kathleen Gray, Patricia Miller, Charlene Coneys, Yarixa Chanza, Monica Sumoza, Victoria M. Caudill, Kelly D. Harris, Courtney A. Manion, Melody J. Lineberger-Moore, Julie J. Wolfe, Barbara J. Rosen, Patricia DiVito, Janet L. Moffat, Christina Michaelis, Prashant Koshy, Diana Perea, Ghaith Al Yacoub, Stephanie Sadeghi, Thomas D. LeGalley, Rudolph F. Evonich, William J. Jean, Gary M. Friesen, John M. Pap, David A. Pesola, Mark D. Cowan, Kristofer M. Dosh, Dianna Larson, Adele M. Price, Jodi A. Nease, Jane E. Anderson, Lori A. Piggott, Robert Iwaoka, Kevin Sharkey, Edward McMillan, Laurie Lowder, Latisha Morgan, Kyle Davis, Tara Caldwell, Erica Breglio, Jasmine Summers, Rachel Poulimas, Muhammad Zahid, Hamid Syed, Maria Escobar, Jacob Levy, Rahma Warsi, Carol Ma, Puxiao Cen, Kimberly A. Cawthon, Delores B. Barnes, Deanna G. Allen, Margaret L. Warrington, Carol R. Stastny, Robin J. Michaels, Mohamad Saleh, John Sorin, Sunny Rathod, Urakay Juett, Steven Spencer, Aziza Keval, Jill McBride, Shane Young, Catherine Baxter, Carol Rasmussen, Shari L. Coxe, Luis Campos, Shahin Tavackoli, Diana Beckham, Darlynee Sanchez, Karanjit Basrai, Dorian Helms, Erica Clinton, Kasie Smith, Henry Cusnir, Mary Klaus Clark, Madhavagopal V. Cherukuri, Ameta Scarfaru, Stephen D. Nash, Loretta C. Grimm, Anna Grace, Kylie McElheran, Dino Subasic, Zedrick Buhay, Janet Litvinoff, Deepak Shah, Shannon Cervantes, Freda Usher, Farra Yasser, Theodore Trusevich, Ronnie L. Garcia, Jamison Wyatt, Rahul Bose, Holllilyn Miska, Traci Spivey, Amy B. Wren, Katie E. Vance, Lani L. Holman, Pam Gibbons, Elaine Eby, Sandra Shepard, Soratree Charoenthongtrakul, Brett Snodgrass, Mohammed Nazem, Shelly Keteenburg, Prathima Murthy, Frederic Prater, Ashley Rumfelt, Christina Eizensmits, Lisa Iannuzzi, Pourus R. Patel, Clellia Bergamino, Elizabeth McFeaters, Botros Rizk, Emiljia Pflaum, Danny Kalish, Rex Ambatali, Mona Ameli, Delaina Sanguinetti, Rakesh Vaidya, Martinus A.W. Broeders, Dorman Henrikus, Adrianus F.M. Kuijper, Nadea Al-Windy, Michael Magro, Karim Hamraoui, Ismail Aksoy, Guy L.J. Vermeiren, H.W.O. Roeters van Lennep, Gerard Hoedemaker, Johannes Jacobus Remmen, Kjell Bogaard, Dirk van der Heijden, Nicole MJ Knufman, Joost Frederiks, Johannes Willem Louwerenburg, Piet van Rossum, Johannes Milhous, Peter van der Meer, Arno van der Weerdt, Rob Breedveld, Mitran Keijzers, Walter Hermans, Ruud van de Wal, Peter A.G. Zwart, Marc M.J.M. van der Linden, Gerardus Zwiers, Dirk J. Boswijk, Jan Geert Tans, Jacob van Eck, Maarten V. Hessen, Barnabas J.B. Hamer, Stieneke Zoet-Nugteren, Lucien Theunissen, E.A. van Beek, Remco Nijmeijer, Pieter R. Nierop, Gerard Linssen, H.P. Swart, Timo Lenderink, Gerard L. Bartels, Frank den Hartog, Brian J. Berg van den, Wouter van Kempen, Susanne Kentgens, Gloria M. Rojas Lingan, Martinus M. Peeters, Hilligje Keterberg, Melchior Nierman, Annemieke K. den Hollander, Jacqueline Hoogendijk, Christine Voors-Pette, Vicdan Kose, Peter Viergever, Larysa Yena, Viktor Syvolap, Mykola P. Kopytsya, Olga Barna, Svitlana S. Panina, Mykhailo I. Lutai, Oxana V. Shershnyova, Iryna Luzkiv, Larysa S. Bula, Sergii Zotov, Ivan Vyjhovaniuk, Olena Lysunets, Volodymyr I. Koshlia, Nataliya Sydor, Myroslava F. Vayda, Olexiy Ushakov, Mykola Rishko, Viktor P. Shcherbak, Yevgeniya Svyshchenko, Vira Tseluyko, Andriy Yagensky, Viktoriia I. Zolotaikina, Olga Godlevska, Larysa Ivanova, Olena Koval, Olena I. Mitchenko, Galyna Y. Kardash, Yurii S. Rudyk, Mykola Stanislavchuk, Volodymyr Ivanovych Volkov, Olena G. Karlinskaya, Susanna A. Tykhonova, Nikolay Vatutin, Ganna Smirnova, Volodymyr M. Kovalenko, Viktor Lizogub, Denys Sebov, Oleksandr Dyadyk, Svetlana Andrievskaya, Mykola P. Krasko, Alexander N. Parkhomenko, Lidiya Horbach, Iryna G. Kupnovytska, Tetyana Pertseva, Oleksandr Karpenko, Dmytro Reshotko, Svitlana V. Zhurba, Leonid Rudenko, Viktoriia Yu Zharinova, Valerii B. Shatylo, Yuriy I. Karpenko, Mariya A. Orynchak, Tatiana R. Kameneva, Elena Zherlitsina, Diana N. Alpenidze, Grigoriy P. Arutyunov, Elena Baranova, Boris Bart, Dmitriy I. Belenkiy, Svetlana A. Boldueva, Elena A. Demchenko, Vera V. Eltishcheva, Alexander M. Gofman, Boris M. Goloshchekin, Ivan Gennadyevich Gordeev, Nikolay Gratsianskiy, Gadel Kamalov, Niyaz R. Khasanov, Irina M. Kholina, Zhanna D. Kobalava, Elena V. Kobeleva, Alexandra O. Konradi, Victor A. Kostenko, Andrey Dmitrievich Kuimov, Polina Y. Ermakova, Sofia K. Malyutina, Alexey V. Panov, Natalia V. Polezhaeva, Olga Reshetko, Nataliya P. Shilkina, Sergey B. Shustov, Elena A. Smolyarchuk, Raisa I. Stryuk, Elena Yurievnar Solovieva, Andrey V. Susekov, Natalia Vezikova, Svetlana N. Ivanova, Alexander A. Petrov, Vladimir O. Konstantinov, Alina S. Agafina, Victor Gurevich, Konstantin N. Zrazhevskiy, Tatiana V. Supryadkina, Nikita B. Perepech, Vadim L. Arkhipovskiy, Dmitry Yu Butko, Irina A. Zobenko, Olga V. Orlikova, Viktor Mordovin, Olga L. Barbarash, Anastasiya Lebedeva, Vladimir Nosov, Oleg V. Averkov, Elena P. Pavlikova, Yuri B. Karpov, Marina Lvovna Giorgadze, Oleg A. Khrustalev, Mikhail Arkhipov, Tatiana A. Raskina, Julia V. Shilko, Yulia Samoilova, Elena D. Kosmacheva, Sergey V. Nedogoda, Kathleen Coetzee, Lesley J. Burgess, F.C.R. Theron, Iftikhar O. Ebrahim, Gerbrand A. Haasbroek, Maria Pretorius, Julien S. Trokis, Dorothea V. Urbach, Mark J. Abelson, Adrian R. Horak, Aysha E. Badat, Ellen M. Makotoko, Hendrik Du Toit Theron, Padaruth Ramlachan, Clive H. Corbett, Ismail H. Mitha, Hendrik F.M. Nortje, Dirkie J. Jansen van Rensburg, Peter J. Sebastian, F.C.J. Bester, Louis J. van Zyl, Brian L. Rayner, Elżbieta Błach, Magda Dąbrowska, Grzegorz Kania, Agata E. Kelm-Warchol, Leszek P. Kinasz, Janusz Korecki, Mariusz Kruk, Ewa Laskowska-Derlaga, Andrzej Madej, Krzysztof Saminski, Katarzyna Wasilewska, Katarzyna Szymkowiak, Małgorzata Wojciechowska, Natalia Piorowska, Andrzej Dyczek, Rajpal K. Abhaichand, Ramesh B. Byrapaneni, Basavanagowdappa Hattur, Malipeddi Bhaskara Rao, Nitin Ghaisas, Sujit Shankar Kadam, Jugal B. Gupta, Santhosh M. Jayadev, V.A. Kothiwale, Atul Mathur, Vijay Bhaskar, Ravi K. Aluri, Udaya P. Ponangi, Mukesh K. Sarna, Sunil Sathe, Manish K. Sharma, Jilendra Pal Singh Sawhney, Chakrabhavi B. Keshavamurthy, Arun Srinivas, Hemant P. Thacker, A. Sharda, Johny Joseph, Sunil Dwivedi, Viswanathan Mohan, Rajendra K. Premchand, Jacques Bedard, Jean Bergeron, Ronald Collette, David Crowley, Richard Dumas, Sam Henein, Geoff Moran, William F. O’Mahony, Michael O’Mahony, Sammy Chan, Mark H. Sherman, Graham C. Wong, Brian D. Carlson, Milan K. Gupta, David Borts, Sean R. Peterson, Martyn Chilvers, Allan J. Kelly, Jean C. Gregoire, Simon Kouz, Josep Rodés Cabau, Minodora Andor, Mircea Cinteza, Radu Ciudin, Radu I. Cojan, Roxana O. Darabont, Dan-Lucian Dumitrascu, Carmen Fierbinteanu-Braticievici, Ana Gabriela Fruntelata, Constantin Militaru, Bogdon E. Minescu, Doina Luminita Serban, Florin Mitu, Dorel Nastase Melicovici, Ovidiu Petrascu, Octavian M. Pirvu, Cristian Podoleanu, Calin Pop, Rodica-Valentina V. Stanescu-Cioranu, Adrian Tase, Cristina Voiculet, Constantine N. Aroney, Anthony M. Dart, Timothy Davis, Karam Kostner, David N. O’Neal, Peter W. Purnell, Bhuwanendu B. Singh, David R. Sullivan, Peter Thompson, Gerald F. Watts, Adam F. Blenkhorn, John V. Amerena, Rafeeq Samie, Randall Hendriks, Joseph Proietto, Nikolai Petrovsky, Alan Whelan, David Colquhoun, Russell S. Scott, Simon C. Young, Tammy Pegg, Samuel JS Wilson, Andrew W. Hamer, Richard A. Luke, Hamish H. Hart, Gerard P. Devlin, Gerard T. Wilkins, Ian F. Ternouth, Samraj Nandra, Bruno S. Loeprich, Nicole McGrath, Stuart L. Tie, Rob J. Bos, Alexandra Wils, Tamara Jacobs, Erik A. Badings, Lillian A. Ebels-Tuinbeek, Mayke L. Scholten, Esther Bayraktar-Verver, Debby Zweers, Manoek Schiks, Carolien Kalkman, Tineke Tiemes, Jeanette Mulderij, Katarzyna Dabrowska, Wilma Wijnakker, Riny Van de Loo, Jeanne de Graauw, Giny Reijnierse, Mirjam van der Zeijst, Mariska Scholten, Henk R. Hofmeijer, Antoinette van Dijk-van der Zanden, Dineke J. van Belle, Jan Van Es, Gera Van Buchem, Wendy Zijda, Harald Verheij, Linnea Oldenhof-Janssen, Martina Bader, Marije Löwik, Sandra Stuij, Pascal Vantrimpont, Krista van Aken, Karen Hamilton, Han Blömer, Gabriela van Laerhoven, Raymond Tukkie, Maarten Janssen, Gerard Verdel, Jon Funke Küpper, Bob van Vlies, Caroline Kalkman, Joke Vooges, Marinella Vermaas, Rachel Langenberg, Niek Haenen, Frans Smeets, Arko Scheepmaker, Marcel Grosfeld, Ilvy Van Lieshout, Marleen van den Berg, Marian Wittekoek, Petra Mol, Antionette Stapel, Margaretha Sierevogel, Nancy van der Ven, Annemiek Berkelmans, Eric Viergever, Hanneke Kramer, Wilma Engelen, Karen V. Houwelingen, Thierry X. Wildbergh, Arend Mosterd, Coriet Hobé-Rap, Marjan van Doorn, Petra Bunschoten, Michel Freericks, Mireille Emans, Petra Den Boer-Penning, Els Verlek, Christine Freericks, Cornelis de Nooijer, Christina Welten, Ingrid Groenenberg, Claudia van der Horst, Esther Vonk, Geert Tjeerdsma, Gerard M. Jochemsen, Corinne van Daalen, Ingrid Y. Danse, Lucy Kuipers, Anke Pieterse, Antonius Oomen, Daan de Waard, Willem Jan Flu, Zusan Kromhout, Petra Van der Bij, Rob Feld, Brigitta Hessels-Linnemeijer, Rob Lardinois, Jan L. Posma, Zwanette R. Aukema-Wouda, Marjolijn Hendriks-van Woerden, Desiree van Wijk, Driek P. Beelen, Ingrid H. Hendriks, Jan J. Jonker, Stefanie Schipperen, Vicdan Köse, Gloria Rojas, Linda Goedhart, Hanneke van Meurs, Jacqueline Rijssemus, Lindy Swinkels-Diepenmaat, Marloes de Louw-Jansen, Dominique Bierens-Peters, Willem W. van Kempen, Marianne E. Wittekoek, Irmaina Agous, Geert Schenk, Janneke Wittekoek, Kevin Cox, Deborah F. Julia, Jan J.C. Jonker, Roel Janssen, Melchor Nierman, Hilligje Katerberg, Irene van der Haar, Willem W. Van Kempen, Taco van Mesdag, Leyda M. Alvarez Costa, Manon Schensema, Salomé Zweekhorst, Deborah Font Julia, Lauri Hanewinckel, Joyce Olsthoorn, Johan C. Berends, Arie C. van der Spek, Roy van der Berg, Rob J. Timmermann, Ingrid Boerema, Iryna Mudruk, Anna Khrystoforova, Serhii Kyselov, Yaroslava V. Hilova, Pavlo Logoida, Nataliia A. Sanina, Ilona P. Golikova, Olena O. Nemchyna, Ivan I. Isaichikov, Olga B. Potapova, Iurii V. Gura, Larysa Berestetska, Olena O. Kulianda, Oleksandr Tantsura, Oleksandr S. Kulbachuk, Volodymyr Petsentiy, Ihor Biskub, Tetyana Handych, Oleg Lagkuti, Alyna Gagarina, Taras Chendey, Oksana F. Bilonko, Olena Matova, Larysa Bezrodna, Olena Yarynkina, Tetiana Ovdiienko, Volodymyr Randchenko, Maryna Mospan, Olena Butko, Olga Romanenko, Mykhailo Pavelko, Iryna Sichkaruk, Svitlana O. Lazareva, Olena A. Kudryk, Inessa M. Koltsun, Tetiana Magdalits, Sergei Zadorozhniy, Kira Kompaniiets, Andrii Ivanov, Sergiy Romanenko, Pavlo Kaplan, Vadym Y. Romanov, Oksana P. Mykytyuk, Nataliia S. Zaitseva, Sergiy N. Pyvovar, Lyudmyla Burdeuna, Emerita Serdobinska, Tatiana I. Shevchenko, Igor I. Ivanytskyi, Olena V. Khyzhnyak, Nataliya Kalinkina, Olena Keting, Olena Sklyanna, Olga Kashanska, Anna Shevelok, Marina Khristichenko, Ievgenii Y. Titov, Danilenko O. Oleksander, Nataliia S. Polenova, Nataliia Altunina, Viktoriia Kororaieva, Stanislav Zborovskiy, Leonid Kholopov, Iurii Suliman, Lanna Lukashenko, Stanislav Shvaykin, Olexandr M. Glavatskiy, Roman O. Sychov, Roman L. Kulynych, Oleksandr A. Skarzhevskyi, Nataliia V. Dovgan, Marta Horbach, Olga Cherkasova, Iryna Tyshchenko, Liudmyla Todoriuk, Svitlana Kizim, Nataliia Brodi, Oleksandr Ivanko, Olga Garbarchuk, Liudmyla Alieksieieva, Tetiana L. Shandra, Olena Beregova, Larisa An Bodretska, Svitlana S. Naskalova, Ivanna A. Antoniuk-Shcheglova, Olena V. Bondarenko, Natalia G. Andreeva, Iryna I. Vakalyuk, Olha S. Chovganyuk, Nataliya R. Artemenko, Kiril A. Maltsev, Natalia Kalishevich, Natalia G. Kondratyeva, Svetlana A. Nikitina, Maria V. Martjanova, Anna V. Sokolova, Dmitrii O. Dragunov, Olga Kolesnik, Vera Larina, Oxana V. Tsygankova, Maria Ivanova, Illia A. Karpov, Elena M. Aronova, Ekaterina S. Vedernikova, Ekaterina I. Lubinskaya, Taras Y. Burak, Sergey I. Skichko, Farhad Rasulev, Ekaterina B. Soldatova, Alexander L. Fenin, Ilya I. Laptev, Elena E. Luchinkina, Alexandr Akatov, Natalia V. Polenova, Natalia N. Slavina, Irina N. Korovnika, Marina Yu Prochorova, Regina Shakirova, Elena N. Andreicheva, Olga A. Krasnova, Tinatin V. Lobzhanidze, Tatiana B. Dmitrova, Viktoriya V. Stakhiv, Maria I. Pechatnikova, Alexandra V. Panova, Maria Y. Tipikina, Oxana P. Rotar, Nikolay A. Bokovin, Saule K. Karabalieva, Farid Y. Tumarov, Elena V. Vasileva, Natalya Gennadevna Lozhkina, Ekaterina V. Filippova, Alisa I. Sharkaeva, Ekanerina V. Filippova Deilik, Natalia Yu Tolkacheva, Elena N. Domracheva, Andrey N. Ryabikov, Inga T. Abesadze, Marianna Z. Alugishvili, Elena P. Nikolaeva, Nadezda V. Smirnova, Valentina I. Rodionova, Polina V. Dolovstaya, Igor E. Yunonin, Sergey V. Kadin, Tatyana S. Sveklina, Anna V. Bushmanova, Elena L. Barkova, Irina S. Gomova, Yana V. Brytkova, Tatiana B. Ivanova, Marina Y. Zubareva, Inga Skopets, Lybov A. Galashevskaya, Emilia D. Butinskaya, Olga G. Gusarova, Natalia B. Kalishevich, Yana R. Pavlova, Marianna P Serebrenitskaya, Vitalina F. Grygorieva, Gulnara R. Kuchaeva, Inna A. Vasileva, Gulnara I. Ospanova, Yulia V. Vahrusheva, Irina A. Semenova, Irina E.E. Mikhailova, Olga O. Kvasova, Valeria D. Shurygina, Alexey E. Rivin, Alexey O. Savelyev, Alexey A. Savelyev, Olesya O. Milyaeva, Nadezhda N. Lapshina, Ninel A. Lantsova, Pavel V. Alexandrov, Evgeniy A. Orlikov, Alla Falkovskaya, Tatiana Ripp, Sergei Triss, Stanislav Pekarskiy, Sitkova Ekaterina, Evgeniya N. Zhuravleva, Olga Perova, Galina Kovaleva, Liubov Koroleva, Lydia Mishchenko, Boris P. Garshin, Svetlana A. Kutuzova, Lyudmila I. Provotorova, Igor P. Zadvorny, Olga V. Okhapkina, Anatoly O. Khrustalev, Tatiana Suvorova, Elena S. Shaf, Varvara A. Vershinina, Andrey A. Kozulin, Oxana A. Oleynik, Irina Y. Martynova, Natalia V. Kizhvatova, Alla S. Salasyuk, Vera V. Tsoma, Alla A. Ledyaeva, Elena V. Chumachek, S.C. Blignaut, Tersia Y. Alexander, Chano Du Plessis, Thirumani Govender, Samatha M. Du Toit, Leya Motala, Areesh Gassiep, Christina Naude (Smit), Marli Terblanche, Marlien Snoer (Kruger), Berenice Pillay, De Vries Basson, Marisa E. Theron, Bianca Fouche, Mareli E. Coetzee, Pieter Odendall, Frederik H. Van Wijk, Anna-Mari Conradie, Trudie Van der Westhuizen, Carine Tredoux, Mohamed S. Mookdam, Andie J. Van der Merwe, Karin Snyman, Gerda Smal, Yvonne De Jager, Thomas A. Mabin, Annusca King, Lindy L. Henley, Brenda M. Zwane, Jane Robinson, Marinda Karsten, Andonia M. Page, Valerie Nsabiyumva, Charmaine Krahenbuhl, Jaiprakash D. Patel, Yunus E. Motala, Ayesha Dawood, Nondumiso B. Koza, Lenore M.S. Peters, Shavashni Ramlachan, Wilhelm J. Bodenstein, Pierre Roux, Lizelle Fouche, Cecilia M. Boshoff, Haroon M. Mitha, Fathima Khan, Henry P. Cyster, Helen Cyster, E. C. Wessels, Florence J. Jacobs, Melanie A. Sebastian, Deborah A. Sebastian, Nadia Mahomed, Ignatius P. Immink, Celia Cotzee, Tanja Cronje, Madele Roscher, Maria Le Roux, Yvonne A. Trinder, Renata Wnętrzak-Michalska, Magdalena Piszczek, Andrzej Piela, Ewa Czernecka, Dorota Knychas, Alina Walczak, Izabella Gładysz, Katarzyna Filas, Ewelina Kiluk, Krzysztof Świgło, Iwona Jędrzejczyk, Kamila Łuczyńska, Katarzyna Tymendorf, Wojciech Piesiewicz, Wojciech L. Kinasz, Stefan Samborski, Ilona Bartuś, Gramzyna Latocha Korecka, Ewa Gulaj, Jolanta Sopa, Bogusław Derlaga, Marcin Baisiak, Allicia Kowalisko, Edyta Stainszewska-Marasazlek, Bartosz Szafran, Malgorzata Swiatkiewicz, Artur Racewicz, Sławomir Grycel, Jerzy Supronik, Sylwia Walendziuk, Magdalena Tarantowicz, Agata Stasiak, Anna Sidorowicz-Białynicka, Marek Dwojak, Ewa Jaźwińska-Tarnawska, Katarzyna Kupczyk, Kamila Martowska, Kamila Kulon, Katarzyna Gajda, Bivin Wilson, Krithika Velusamy, Swaidha S. Sadhiq, Bhavani Siddeshi, M. Bhanukumar, Abhishek Srivatsav, Madhan Ramesh, Sri Harsha Chalasani, Mini Johnson, Prashanth Gopu, Jeesa George, Sowmya Reddy, Swetha Tessy Thara Eleena, Damodara Rao Kodem, Haritha N. Nakkella, Padma Kumari Mandula, Anjan Kumar Vuriya, Syamala Rajana, Aruna Kale, Tiwari Rajeev, Raina Jain, Vipin Jain, Srilakshmi Mandayam Adhyapak, Lumin Sheeba, Uma C R, Ramya R, Aditya V. Kulkarni, M.S. Ganachari, Ruma Sambrekar, Mohammad Bilal, Kalyan Chakravarthy, Ravi Badhavath, Sravan Kumar, Meenakshi Simhadri, Farooque Salamuddin, Venkat Prasad, Vivek Dwivedi, Sudha Sarna, Tilak Arora, Deepak Chawla, Archana Sathe, Chaware Gayatree, Ajeet Nanda, Ram Avtar, Jyoti Sharma, Vaibhavi P S, Sasirekha D, Deepthi Kobbajji, Ramya Ningappa, Shwetha Shree, Chandrashekar K, Nandini M R, Sowjanya S, Devika I G, Yashaswini N, Sonika G, Rathna L, Priyanka R, Rupal J. Shrimanker, Lakshmi Vinutha Reddy, K. Sumathi, Babitha Devi, Bina N. Naik, Rohini Manjunath, Rajeshwari Ashok, Tony V. Kunjumon, Jesline Thomas, Shaik Samdhani, Kasthuri Selvam, Poongothai Subramani, Nandakumar Parthasarathy, Nirmal K. Bohra, Anvesh K. Gatla, Cheryl Horbatuk, Julie Sills, E B. Davey, Liz Paramonczyk, Olga Racanelli, Sandy Strybosch, Andre Belanger, Jean Palardy, Alicia Schiffrin, Sylvie Gauthier, Norman Kalyniuk, Shawn D. Whatley, Heather Lappala, Grishma Patel, Matthew Reeve, Catherine Moran, Jody Everitt, Teresa Ferrari, Christine Bouffard, Jirir Frohlich, Gordon Francis, John Mancini, Gregory Bondy, Debbie DeAngelis, Patricia Fulton, David W. Blank, Angela Lombardo, Mylène Roy, Jackie Chow, Hyman Fox, William J. Grootendorst, Angela Hutchinson, Sharon M. Chan, Christie Fitzgerald, Lynn Wilkins, Rebecca L. Raymond, Arlene Reyes, Lavoie Marc André, Denis Fortin, Hélène Ouimet, Thanh-Thao Tôn-Nu, Martine Dussureault, Marie-Hélène Blain, Madeleine Roy, Nathalie Kopajko, Chantal Fleury, Karine Maheux, Gabriela Valentina Ciobotaru, Maria C. Constantinescu, Carmen-Lucia Gherghinescu, Ana-Maria Avram, Ioan Manitiu, Aura Sinpetrean, Lucian Pop, Delia Lupu, Radu Usvat, Ana Petrisor, Nicoleta Dumitru, Camelia Moruju, Adelina Gheorghita, Magda V. Mitu, Cosmin Macarie, Ana Maria Pop, Maria-Catalina Diaconu, Iulia Grancea, Mihaela Cosma, Mihaela Crisan, Elizabeth Herron, Paul Nestel, Sally B. Kay, Kaye S. Carter, Imran Badshah, Ashley Makepeace, Jocelyn Drinkwater, Michelle England, Azette Rafei, Kylie Patterson, Alicia Jenkins, Sybil McAuley, Sue M. Kent, Joy E. Vibert, Leonie Perrett, Thomas David, Samantha L. Kaye, Monika O’Connor, Nimalie J. Perera, Nicole T. Lai, Kerry A. Kearins, Christinia Dicamillo, Heather Anderson, Louise Ferguson, Sharon D. Radtke, Charles T. Thamarappillil, Janice M. Boys, Anita K. Long, Toni Shanahan, Michael Nyguyen, Nicole Forrest, Gill Tulloch, Della Greenwell, Sarah L. Price, Aye N. Tint, Priya K. Sumithran, Tamara L. Debreceni, Lisa Walker, Mary Caruana, Kira Edwards, Maria Stathopoulos, Cilla Haywood, Dimitar Sajkov, Sharen Pringle, Anne Tabner, Kathrina Bartolay, Chamindi Abeyratne, Kylie Bragg, Patrick Mulhern, Peter Purnell, Lyn Williams, Jane Hamlyn, Aurelia Connelly, Jan Hoffman, Samantha Bailey, Jane Kerr, Zarnia Morrison, Sarah Maeder, Roberta McEwan, Prasanna Kunasekera, Patrice McGregor, Jo Young, Sharon Berry, Rick Cutfield, Michelle Choe, Catherine McNamara, Narrinder K. Shergill, Petra Crone, Miles G. Williams, Keith Dyson, Diana H. Schmid, Audrey C. Doak, Melissa Spooner, Colin Edwards, Anne Turner, Grainne M. McAnnalley, Raewyn A. Fisher, Fraser B. Hamilton, Denis H. Friedlander, Melissa R. Kirk, Jayne E. Scales, Marguerite A. McLelland, Neelam A. Dalman, Cathy E. Vickers, Carolyn Jackson, Wendy Coleman, Phillip I. Garden, and Wendy F. Arnold

Subjects
Male, medicine.medical_specialty, Rate ratio, Double-Blind Method, Ischemia, Risk Factors, Physiology (medical), Internal medicine, medicine, Clinical endpoint, Humans, Myocardial infarction, Coronary Artery Bypass, Stroke, Aged, business.industry, Unstable angina, Hazard ratio, Absolute risk reduction, Middle Aged, medicine.disease, Eicosapentaenoic Acid, Number needed to treat, Cardiology, Female, Cardiology and Cardiovascular Medicine, business
Abstract

Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.

Published
2021
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78. Edoxaban versus Vitamin K Antagonist for Atrial Fibrillation after TAVR

Author

Thomas Pilgrim, Diego López-Otero, José Luis Zamorano, James Jin, Roxana Mehran, Cathy Chen, Peter Nordbeck, Eric Boersma, Envisage-Tavi Af Investigators, Holger Thiele, Christian Hengstenberg, Rainer Hambrecht, Fayaz A. Shawl, George Dangas, Nicolas M. Van Mieghem, Luis Nombela-Franco, Kentaro Hayashida, Piera Capranzano, Anil Duggal, Yusuke Watanabe, Pascal Vranckx, Josep Rodés-Cabau, Raul Moreno, Usman Baber, Roland Veltkamp, Petra Laeis, Marco Valgimigli, Hyo-Soo Kim, Felix Meincke, Richard A. Anderson, Patrick Ohlmann, Irene Lang, Hans Lanz, Masanori Yamamoto, Helge Möllmann, Shigeru Saito, Martin Unverdorben, and Cardiology

Subjects
Male, medicine.medical_specialty, Gastrointestinal bleeding, Vitamin K, Pyridines, medicine.drug_class, Kaplan-Meier Estimate, Transcatheter Aortic Valve Replacement, chemistry.chemical_compound, Postoperative Complications, Edoxaban, Thromboembolism, Internal medicine, Atrial Fibrillation, 80 and over, Humans, Medicine, Myocardial infarction, Mortality, 610 Medicine & health, Stroke, Aged, Aged, 80 and over, business.industry, Hazard ratio, Anticoagulants, Phenindione, Atrial fibrillation, 4-Hydroxycoumarins, General Medicine, Vitamin K antagonist, medicine.disease, Confidence interval, Intention to Treat Analysis, Thiazoles, chemistry, Cardiology, Female, Gastrointestinal Hemorrhage, business, Factor Xa Inhibitors
Abstract

BACKGROUND The role of direct oral anticoagulants as compared with vitamin K antagonists for atrial fibrillation after successful transcatheter aortic-valve replacement (TAVR) has not been well studied. METHODS We conducted a multicenter, prospective, randomized, open-label, adjudicator-masked trial comparing edoxaban with vitamin K antagonists in patients with prevalent or incident atrial fibrillation as the indication for oral anticoagulation after successful TAVR. The primary efficacy outcome was a composite of adverse events consisting of death from any cause, myocardial infarction, ischemic stroke, systemic thromboembolism, valve thrombosis, or major bleeding. The primary safety outcome was major bleeding. On the basis of a hierarchical testing plan, the primary efficacy and safety outcomes were tested sequentially for noninferiority, with noninferiority of edoxaban established if the upper boundary of the 95% confidence interval for the hazard ratio did not exceed 1.38. Superiority testing of edoxaban for efficacy would follow if noninferiority and superiority were established for major bleeding. RESULTS A total of 1426 patients were enrolled (713 in each group). The mean age of the patients was 82.1 years, and 47.5% of the patients were women. Almost all the patients had atrial fibrillation before TAVR. The rate of the composite primary efficacy outcome was 17.3 per 100 person-years in the edoxaban group and 16.5 per 100 person-years in the vitamin K antagonist group (hazard ratio, 1.05; 95% confidence interval [CI], 0.85 to 1.31; P���=���0.01 for noninferiority). Rates of major bleeding were 9.7 per 100 person-years and 7.0 per 100 person-years, respectively (hazard ratio, 1.40; 95% CI, 1.03 to 1.91; P���=���0.93 for noninferiority); the difference between groups was mainly due to more gastrointestinal bleeding with edoxaban. Rates of death from any cause or stroke were 10.0 per 100 person-years in the edoxaban group and 11.7 per 100 person-years in the vitamin K antagonist group (hazard ratio, 0.85; 95% CI, 0.66 to 1.11). CONCLUSIONS In patients with mainly prevalent atrial fibrillation who underwent successful TAVR, edoxaban was noninferior to vitamin K antagonists as determined by a hazard ratio margin of 38% for a composite primary outcome of adverse clinical events. The incidence of major bleeding was higher with edoxaban than with vitamin K antagonists. (Funded by Daiichi Sankyo; ENVISAGE-TAVI AF ClinicalTrials.gov number, NCT02943785.).

Published
2021
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79. A systematic review and meta-analysis of the efficacy of topical sphincterotomy treatments for anal fissure

Author

Molly-Olivia Hardy, Maree Weston, Hanson Unasa, Melbourne Mauiliu-Wallis, Primal P. Singh, Andrew G. Hill, Andrew B. Connolly, and James Jin

Subjects
medicine.medical_specialty, Anal fissure, business.industry, Visual analogue scale, Gastroenterology, Placebo, medicine.disease, law.invention, Systematic review, Randomized controlled trial, law, Meta-analysis, Relative risk, Internal medicine, medicine, Diltiazem, business, medicine.drug
Abstract

Anal fissure is a common condition that can be treated medically or surgically. Chemical sphincterotomy is often used before surgical intervention. This study aims to evaluate the effectiveness of topical agents for chemical sphincterotomy on healing of anal fissures and side-effects. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) compliant systematic review was performed using MEDLINE, EMBASE, Scopus, and CENTRAL databases. Eligible studies included randomized controlled trials which compared topical sphincterotomy agents with topical placebo agents or each other. Studies that included surgical treatments were excluded. Overall evidence was synthesized according to the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Thirty-seven studies met the study selection criteria. Seventeen studies show that glyceryl trinitrate (GTN) was significantly more likely to heal anal fissure than placebo (relative risk (RR) = 1.96, 95% confidence interval (95%CI) = 1.35–2.84, I2 = 80%). Eleven studies showed a marginally significant difference between healing rates for diltiazem vs GTN, RR = 1.16, (1.01–1.33) I2 = 48%. There was no significant difference in healing between diltiazem and placebo, RR = 1.65, (0.64–4.23), I2 = 92%. GTN significantly reduced pain on the visual analog scale compared to the placebo group, MD–0.97 (–1.64 to –0.29) I2 = 92%. There was high certainty of evidence that GTN was significantly more likely to cause headache than placebo (RR = 2.73 (1.82–4.10) I2 = 58%) and diltiazem RR = 6.88 (2.19–21.63) I2 = 17%. There is low certainty evidence topical nitrates are an effective treatment for anal fissure healing and pain reduction compared to placebo. Despite widespread use of topical diltiazem, more evidence is required to establish the effectiveness of calcium channel blockers compared to placebo.

Published
2021
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81. An Artificial Intelligence URL Parser for Safer Web Browsing and Detection of Suspicious Links

Author

Yu Sun, Gayatri S, and James Jin

Subjects
World Wide Web, Parsing, Computer science, SAFER, Web navigation, computer.software_genre, computer
Abstract

With more than seven billion people actively using the Internet, the number of cyber attacks has increased, and personal data breaches have become a concern among the general public. The COVID-19 pandemic has only increased the use of online platforms and services for work and leisure activities, which opens the door to more scams, viruses, and other cyber security breaches. Guided by SEO techniques and research regarding dangerous website and domain patterns, we have designed and implemented a visual system that tracks suspicious links on an active webpage and marks them in order to alert users to proceed with caution. Our AI utilizes linear regression to best detect trends in URL parsing, comparing them with registered unsafe links to see if they pose similar threats. The results reveal that AI isn’t entirely accurate since some trends are hard to decipher; however, it can reliably flag certain redirects and out-of-domain links that would otherwise remain hidden to users.

Published
2021
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82. Effectiveness of Quality Improvement Processes, Interventions, and Structure in Trauma Systems in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis

Author

Andrew G. Hill, Jaymie Ang Henry, Cheng Har Yip, Salesi 'Akau'ola, Mira Mehes, Guidelines for Quality Safe Surgery, Emmanuel A. Ameh, Iferemi Waiqanabete, Peter M. Nthumba, James Jin, Stijn de Jonge, Graduate School, Surgery, ACS - Heart failure & arrhythmias, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism

Subjects
medicine.medical_specialty, education.field_of_study, Quality management, business.industry, Population, Psychological intervention, MEDLINE, Developing country, 030230 surgery, 03 medical and health sciences, 0302 clinical medicine, Systematic review, 030220 oncology & carcinogenesis, Relative risk, Meta-analysis, Emergency medicine, Medicine, Surgery, business, education
Abstract

Background: Trauma mortality in low- and middle-income countries (LMICs) remains high compared to high-income countries. Quality improvement processes, interventions, and structure are essential in the effort to decrease trauma mortality. Methods: A systematic review and meta-analysis of interventional studies assessing quality improvement processes, interventions, and structure in developing country trauma systems was conducted from November 1989 to August 2020 according to the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were included if they were conducted in an LMIC population according to World Bank Income Classification, occurred in a trauma setting, and measured the effect of implementation and its impact. The primary outcome was trauma mortality. Results: Of 37,575 search results, 30 studies were included from 15 LMICs covering five WHO regions in a qualitative synthesis. Twenty-seven articles were included in a meta-analysis. Implementing a pre-hospital trauma system reduced overall trauma mortality by 45% (risk ratio (RR) 0.55, 95% CI 0.4 to 0.75). Training first responders resulted in an overall decrease in mortality (RR 0.47, 95% CI 0.28 to 0.78). In-hospital trauma training with certified courses resulted in a reduction of mortality (RR 0.71, 95% CI 0.62 to 0.78). Trauma audits and trauma protocols resulted in varying improvements in trauma mortality. Conclusion: There is evidence that quality improvement processes, interventions, and structure can improve mortality in the trauma systems in LMICs.

Published
2021
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83. Edoxaban vs. Vitamin K Antagonist for Atrial Fibrillation After Transcatheter Aortic Valve Replacement in Japanese Patients - A Subanalysis of the ENVISAGE-TAVI AF Trial

Author

Yusuke Watanabe, Kentaro Hayashida, Masanori Yamamoto, Futoshi Yamanaka, Kazumasa Yamasaki, Toru Naganuma, Yohei Ohno, Masahiro Yamawaki, Nobuyuki Morioka, Kazuki Mizutani, Norio Tada, Hiroshi Ueno, Hidetaka Nishina, Masaki Izumo, Yoshifumi Nakajima, Kenji Ando, Kensuke Takagi, Tetsuya Kimura, Kumiko Sugio, George Dangas, Nicolas M Van Mieghem, Christian Hengstenberg, Cathy Chen, James Jin, Martin Unverdorben, Shigeru Saito, and Cardiology

Subjects
Aged, 80 and over, Male, Vitamin K, Anticoagulants, Hemorrhage, General Medicine, Transcatheter Aortic Valve Replacement, Stroke, Treatment Outcome, Fibrinolytic Agents, Japan, Atrial Fibrillation, Humans, Female, Prospective Studies, Cardiology and Cardiovascular Medicine, Ischemic Stroke
Abstract

BACKGROUND: Japanese patients undergoing transcatheter aortic valve replacement (TAVR) are often female and have a small body size, potentially impacting bleeding risk with antithrombotic therapy. Outcomes of direct oral anticoagulant use in these patients with atrial fibrillation (AF) need to be clarified.Methods and Results: This prespecified analysis included Japanese patients from ENVISAGE-TAVI AF, a prospective, randomized, open-label, adjudicator-masked trial that compared treatment with edoxaban and vitamin K antagonists (VKAs) in patients with AF after TAVR. The primary efficacy and safety outcomes were net adverse clinical events (NACE; composite of all-cause death, myocardial infarction, ischemic stroke, systemic embolic event, valve thrombosis, and International Society on Thrombosis and Haemostasis [ISTH]-defined major bleeding) and ISTH-defined major bleeding, respectively. Intention-to-treat (ITT) and on-treatment analyses were performed. Overall, 159 Japanese patients were enrolled (edoxaban group: 82, VKA group: 77) and followed for on average 483 days. Mean patient age was 83.8 years; 52.2% were female. In the ITT analysis, NACE rates were 10.9%/year with edoxaban and 12.5%/year with VKA (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.38-1.90); major bleeding occurred in 8.9%/year and 7.3%/year, respectively (HR, 1.17; 95% CI, 0.45-3.05). In edoxaban- and VKA-treated patients, rates of ischemic stroke were 1.8%/year and 1.0%/year, respectively; fatal bleeding rates were 0.9%/year and 2.0 %/year. On-treatment results were similar to ITT. CONCLUSIONS: In Japanese patients with AF after successful TAVR, edoxaban and VKA treatment have similar safety and efficacy profiles.

Published
2022

84. Abstract 5209: Generation of humanized TREM2 mice for preclinical evaluation of therapeutics targeting tumor-associated macrophages

Author

Ruili Lv, Jia Yu, Zhiyuan Shen, and James Jin

Subjects
Cancer Research, Oncology
Abstract

In recent years, immune checkpoint inhibitors (ICIs) have improved treatment for several types of cancer. However, the overall response rates remain low, and drug resistance can occur in patients after initial responses. This resistance is thought to be due in part to tumor-associated macrophages (TAMs), which can deploy a number of mechanisms to suppress anti-tumor immunity, resulting in tumor immune escape. Triggering receptor expressed on myeloid cells-2 (TREM2), a transmembrane receptor that is part of the immunoglobulin superfamily, is highly expressed on the surface of TAMs. Moreover, the expression level of TREM2 is reported to be higher in cancerous tissues vs normal tissues, with higher expression associated with poorer patient outcomes across multiple solid tumor types. Conversely, mice that lack Trem2 experience slower tumor cell expansion and are more responsive to anti-PD-1 immunotherapy, suggesting that TREM2 may be a promising therapeutic target for improving responses to ICI immunotherapies. To better assist the efficacy evaluation of anti TREM2 antibodies, Biocytogen has generated a humanized TREM2 mouse model. In these mice, exons 1-5 and the 3’UTR of mouse Trem2 gene, which encodes the full-length protein, were replaced by its human counterpart. In homozygous mice, human TREM2 protein expression is detected. The distribution of basal leukocyte subpopulations of blood, spleen, and lymph nodes in humanized B-hTREM2 mice were similar and comparable to those in wild-type C57BL/6 mice. Using the MC38 tumor model, we showed modest efficacy of an anti-human TREM2 antibody in inhibiting tumor growth in vivo. In summary, TREM2 humanized mice provide a powerful preclinical model for in vivo evaluation of anti-human TREM2 antibodies for cancer treatment. Citation Format: Ruili Lv, Jia Yu, Zhiyuan Shen, James Jin. Generation of humanized TREM2 mice for preclinical evaluation of therapeutics targeting tumor-associated macrophages. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5209.

Published
2023
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85. Abstract 5320: The RenMice™ HiTS (Hyperimmune target specific) Platform facilitates identification of novel therapeutic antibodies for challenging targets

Author

Xiaoqian Zhang, Shufang Fu, Shujin Zhang, Xin Ji, Li Hui, James Jin, and Jing Zhang

Subjects
Cancer Research, Oncology
Abstract

In recent years, an increasing number of therapeutic antibodies have shown to be effective for the treatment of cancer and other diseases. However, limitations in the traditional discovery process, including immune tolerance of highly homologous genes, challenges with antibody sequence humanization, clone selection, and model selection for drug efficacy and safety evaluation, often hinder the process of identifying new therapeutic antibodies. The RenMice™ HiTS (Hyperimmune Target Specific) Platform is a library of chromosome engineered mice with fully human immunoglobulin variable domains replacing the mouse loci, each with a specific drug target gene knocked out. These mice are designed to establish robust immune responses and generate antibodies that bind to more epitopes of the target protein, including conserved domains. The platform is ideal for challenging targets, such as proteins with high homology across species, or multi-pass transmembrane proteins (e.g. GPCRs/ion channels). Here, we show that the platform can be used to generate antibodies that cross-react with multiple species, like human, monkey, dog, and mouse targets, by immunizing with both human and mouse or dog antigen. We provide examples for newer campaigns, including species cross-reactivity and internalization of novel antibodies targeting NECTIN-4, and high-throughput in vivo efficacy screening of novel anti-PD-1 antibodies in wild-type mice. In the future, we will evaluate the preliminary toxicity of these cross-reactive antibodies in preclinical animal models. Thus, selection of the best antibody candidate based on in vivo efficacy and safety allows for a streamlined and successful preclinical phase. In conclusion, the RenMice™ HiTS platform facilitates the generation of developable antibodies that recognize novel epitopes and challenging targets. Citation Format: Xiaoqian Zhang, Shufang Fu, Shujin Zhang, Xin Ji, Li Hui, James Jin, Jing Zhang. The RenMice™ HiTS (Hyperimmune target specific) Platform facilitates identification of novel therapeutic antibodies for challenging targets. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5320.

Published
2023
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86. Abstract 3233: A novel triple humanized B-hPD-1/hPD-L1/hCCR8 mouse model to evaluate in vivo efficacy of combination therapies

Author

Linlin Wang, Xiao Liu, James Jin, and Yuxiang Yu

Subjects
Cancer Research, Oncology
Abstract

Regulatory T cells (Tregs) play an immunosuppressive role in the tumor microenvironment (TME), such that altering or depleting Treg function has emerged as an important anti-tumor strategy. Targeting CCR8, which is highly expressed in tumor-infiltrating Tregs, has shown its potency in reducing tumor burden and increasing responsiveness to immune-checkpoint blockade therapy. Collectively, this suggests a need for preclinical models that support Treg-targeted therapies. To address this, Biocytogen developed a triple humanized (B-hPD-1/hPD-L1/hCCR8) mouse model to evaluate in vivo efficacy of combination therapies. In this model, the full coding sequence of murine Ccr8 was replaced by the full coding sequence of human CCR8, while murine Pd-1 and Pd-l1 IgV domains were replaced by their human counterpart gene sequences. Human PD-1 and PD-L1 protein expression was confirmed in B-hPD-1/hPD-L1/hCCR8 mice by flow cytometry, and human CCR8 protein expression was observed in MC38 tumors harvested from B-hPD-1/hPD-L1/hCCR8 mice. Finally, combination therapy using anti-human PD-1 and anti-human CCR8 antibodies were effective in controlling B-hPD-L1 MC38 tumor growth in B-hPD-1/hPD-L1/hCCR8 mice. Altogether, this line provides a powerful preclinical model for in vivo evaluation of therapeutic antibodies. Citation Format: Linlin Wang, Xiao Liu, James Jin, Yuxiang Yu. A novel triple humanized B-hPD-1/hPD-L1/hCCR8 mouse model to evaluate in vivo efficacy of combination therapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3233.

Published
2023
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87. Abstract 5178: Humanized OX40/OX40L mice as a tool for evaluating novel therapeutics

Author

Chonghui Liu, Jiawei Yao, Xiaofei Zhou, James Jin, and Zan Zhang

Subjects
Cancer Research, Oncology
Abstract

The use of immune-competent mouse models that express target human genes provide a promising preclinical platform aimed at developing novel immunotherapies. Emerging immunotherapies include targeting OX40 and OX40 ligand (OX40L), which can lead to enhanced T cell activation, proliferation, and effector function. Blocking the OX40/OX40L pathway improves autoantigen-specific T cell responses and decreases immunocompetence across several autoimmune diseases. To explore the potential of OX40 and OX40L antibody efficacy studies, we developed double humanized B-hOX40/hOX40L mice by replacing the extracellular domain sequences of murine Ox40 and Ox40l with the corresponding human sequences. We validated human OX40L gene expression by RT-PCR and OX40/OX40L protein expression by flow cytometry in B-hOX40/hOX40L mice. Additionally, percentages of splenic, blood, and lymph node immune cells were similar between B-hOX40/hOX40L and wild-type C57BL/6 mice. Altogether, this data demonstrates that B-hOX40/hOX40L mice are suitable for in vivo efficacy studies using anti-human OX40 and OX40L antibodies. Citation Format: Chonghui Liu, Jiawei Yao, Xiaofei Zhou, James Jin, Zan Zhang. Humanized OX40/OX40L mice as a tool for evaluating novel therapeutics. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5178.

Published
2023
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89. Enhanced heart rate prediction model using damped least-squares algorithm

Author

An, Angela, Al-Fawa’reh, Mohammad, Kang, James Jin, An, Angela, Al-Fawa’reh, Mohammad, and Kang, James Jin

Abstract

Monitoring a patient’s vital signs is considered one of the most challenging problems in telehealth systems, especially when patients reside in remote locations. Companies now use IoT devices such as wearable devices to participate in telehealth systems. However, the steady adoption of wearables can result in a significant increase in the volume of data being collected and transmitted. As these devices run on limited battery power, they can run out of power quickly due to the high processing requirements of the device for data collection and transmission. Given the importance of medical data, it is imperative that all transmitted data adhere to strict integrity and availability requirements. Reducing the volume of healthcare data and the frequency of transmission can improve a device’s battery life via an inference algorithm. Furthermore, this approach creates issues for improving transmission metrics related to accuracy and efficiency, which are traded-off against each other, with increasing accuracy reducing efficiency. This paper demonstrates that machine learning (ML) can be used to overcome the trade-off problem. The damped least-squares algorithm (DLSA) is used to enhance both metrics by taking fewer samples for transmission whilst maintaining accuracy. The algorithm is tested with a standard heart rate dataset to compare the metrics. The results showed that the DLSA provides the best performance, with an efficiency of 3.33 times for reduced sample data size and an accuracy of 95.6 %, with similar accuracies observed in seven different sampling cases adopted for testing that demonstrate improved efficiency. This proposed method significantly improve both metrics using ML without sacrificing one metric over the other compared to existing methods with high efficiency.

Published
2022

93. Epidemiology of haemorrhoids and publicly funded excisional haemorrhoidectomies in New Zealand (2007–2016): a population‐based cross‐sectional study

Author

Weisi Xia, Ahmed W.H. Barazanchi, Tarik Sammour, Andrew G. Hill, Christin Coomarasamy, James Jin, and Andrew D. MacCormick

Subjects
Adult, Hemorrhoidectomy, medicine.medical_specialty, education.field_of_study, business.industry, Cross-sectional study, Incidence, Incidence (epidemiology), Population, Gastroenterology, Ethnic group, Population based, Hemorrhoids, Cross-Sectional Studies, Epidemiology, Public hospital, medicine, Humans, Outpatient clinic, Female, education, business, New Zealand, Demography
Abstract

AIM Haemorrhoids are frequently encountered by the general or colorectal surgeon. Although a benign disease, those with symptomatic, advanced grades frequently require excisional haemorrhoidectomy for definitive management. Despite their widespread nature, the epidemiological burden of haemorrhoids and haemorrhoidectomies on populations is not well described. This study seeks to establish the incidence of both haemorrhoids diagnosed and haemorrhoidectomies performed in New Zealand. METHOD This is a population-based cross-sectional study examining the incidence of all patients who were newly diagnosed with haemorrhoids in New Zealand public hospital outpatient clinics and those who received excisional haemorrhoidectomy in New Zealand public hospitals from 2007 to 2016. Data were extracted and linked using the New Zealand National Minimum Dataset and the National Non-Admitted Patient Collection. Variables collected included age group, sex, ethnicity and geographical location. RESULTS A total of 46 095 recorded diagnoses of haemorrhoids were made, with a total of 18 739 haemorrhoidectomies in the 10-year period recorded. The incidence rate of diagnosis increased from 84.6 to 120.5 per 100 000 and the incidence rate of haemorrhoidectomies performed from 30.4 to 51.1 per 100 000, a significantly increased annual incidence. There was a unimodal peak prevalence in the fifth decade of life with women more affected. Europeans formed the largest group affected, with Asians showing the highest rate of increased incidence. CONCLUSION There is an increasing incidence of patients with symptomatic haemorrhoids presenting to the New Zealand public healthcare system, with a preponderance in working age adults, especially women.

Published
2020
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94. Symptom‐based scoring for haemorrhoidal disease: a systematic review

Author

Andrew B. Connolly, Weisi Xia, James Jin, and Andrew G. Hill

Subjects
medicine.medical_specialty, Scoring system, media_common.quotation_subject, Disease, Hemorrhoids, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Surveys and Questionnaires, Humans, Medicine, Quality (business), Patient Reported Outcome Measures, Disease burden, media_common, business.industry, Gastroenterology, Reproducibility of Results, Systematic review, 030220 oncology & carcinogenesis, Cohort, Quality of Life, Physical therapy, 030211 gastroenterology & hepatology, business, Symptom score
Abstract

Aim Haemorrhoidal disease can severely affect a patient's quality of life. Its classification is commonly based on morphology of the degree of prolapse; however, this does not take into account the symptoms and impact on the quality of life. The aim of this systematic review was to determine the most appropriate instruments that classify the severity of disease according to symptoms. Method A PRISMA-compliant search was conducted in December 2019 to identify studies that described the validation of a haemorrhoidal symptom score. The measurement properties of the scoring systems were assessed based on the consensus-based standards for the selection of health status measurement instruments (COSMIN) methodology for systematic reviews for patient-reported outcome measures. Results A total of 5288 articles were identified, with five articles included. Three studies developed a scoring system based on a set of core symptoms for a cohort of patients and validated the score against treatment outcomes. One study developed a disease-specific quality of life questionnaire based on symptoms to evaluate disease burden. One study combined both quality of life and symptom measures and tested measurement properties on two cohorts of patients. Only one study demonstrated satisfactory valid, reliable and responsive measurement criteria. Conclusion A single study demonstrated sufficient quality in measurement properties to be recommended for clinical use. Further studies in this area should utilize consensus-based standards for designing and reporting validation research to ensure that the appropriate evidence base is acquired if any further patient-reported outcome measures are to be recommended.

Published
2020
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95. No Soldiers Left Behind: An IoT-Based Low-Power Military Mobile Health System Design

Author

Gordana Dermody, Paul Haskell-Dowland, James Jin Kang, Mohammadreza Ghasemian, Wencheng Yang, and Sasan Adibi

Subjects
LPWAN, General Computer Science, Computer science, Real-time computing, Wearable computer, 02 engineering and technology, multilayer inference system (MIS), 0202 electrical engineering, electronic engineering, information engineering, Wireless, wireless body area network (WBAN), General Materials Science, Electrical and Electronic Engineering, mobile health (mHealth), Authentication, business.industry, General Engineering, 020206 networking & telecommunications, emergency alarm notification, Sensor fusion, Networking hardware, low power wide area network (LPWAN), Systems design, 020201 artificial intelligence & image processing, lcsh:Electrical engineering. Electronics. Nuclear engineering, business, Multilayer inference algorithm (MIA), lcsh:TK1-9971
Abstract

There has been an increasing prevalence of ad-hoc networks for various purposes and applications. These include Low Power Wide Area Networks (LPWAN) and Wireless Body Area Networks (WBAN) which have emerging applications in health monitoring as well as user location tracking in emergency settings. Further applications can include real-time actuation of IoT equipment, and activation of emergency alarms through the inference of a user's situation using sensors and personal devices through a LPWAN. This has potential benefits for military networks and applications regarding the health of soldiers and field personnel during a mission. Due to the wireless nature of ad-hoc network devices, it is crucial to conserve battery power for sensors and equipment which transmit data to a central server. An inference system can be applied to devices to reduce data size for transfer and subsequently reduce battery consumption, however this could result in compromising accuracy. This paper presents a framework for secure automated messaging and data fusion as a solution to address the challenges of requiring data size reduction whilst maintaining a satisfactory accuracy rate. A Multilayer Inference System (MIS) was used to conserve the battery power of devices such as wearables and sensor devices. The results for this system showed a data reduction of 97.9% whilst maintaining satisfactory accuracy against existing single layer inference methods. Authentication accuracy can be further enhanced with additional biometrics and health data information.

Published
2020
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96. Changing the routine: a move to patient initiated follow up to improve surgical outpatient clinic

Author

Joshua Balhorn, Bruce Su'a, James Jin, Sze‐Lin Peng, Maree Weston, Lincoln Israel, Andrew Connolly, Andrew G. Hill, and Ashish Taneja

Subjects
Appointments and Schedules, Humans, Surgery, General Medicine, Colorectal Neoplasms, Ambulatory Care Facilities, Referral and Consultation, Follow-Up Studies
Abstract

Patient initiated follow up (PIFU) allows patients to initiate a hospital follow up appointment on an 'as required' basis in contrast to the traditional physician-initiated model. We present a clinical pathway for patients referred with rectal bleeding at a large tertiary public hospital in South Auckland, New Zealand and demonstrate the utility of PIFU and its impact on reducing follow up appointments.The purpose of the pathway was to allow standardized care by the clinicians and allow for PIFU. Two separate protocols were developed - 'Painful PR bleeding' and 'Painless PR bleeding'. A new clinic (NC) was started following these protocols, and this was compared to historical controls (HC). The primary outcome was the rate of follow up appointments.There were 133 patients in the NC and 135 in the HC, with significantly less follow ups in the NC (6% versus 45%, p 0.0001). A small percentage of patients in the NC group were directly discharged (10%) whilst 70% of patients were discharged with a PIFU card. Thirty phone calls were made using PIFU, with 10 patients returning to clinic and 20 requiring advice and reassurance only. At 5 year follow up, there was a single colorectal malignancy found in both groups.Initiating a protocol that includes patient initiated follow up vastly reduces the need for routine return to clinic for the majority of patients, without sacrificing patient care. A protocolised approach to clinic for other areas in general surgery should be considered.

Published
2022

97. Evaluation of the inflammatory profile following uncomplicated elective colectomy

Author

Bruce Su'a, Tony Milne, Rebekah Jaung, Weisi Xia, James Jin, Darren Svirskis, Tim Eglinton, Ian Bissett, and Andrew G. Hill

Subjects
Adult, Postoperative Complications, Interleukin-6, Tumor Necrosis Factor-alpha, Humans, Surgery, Laparoscopy, General Medicine, Prospective Studies, Colectomy, Interleukin-10, Retrospective Studies
Abstract

Attenuation of the inflammatory response in patients undergoing colectomy with modern perioperative care and laparoscopic surgery has been a focus of research in recent years. Despite reported benefits, significant heterogeneity remains with studies including patients undergoing both rectal and colon surgery and including surgery with postoperative complications. Therefore, the aim of the study was to evaluate the inflammatory response in patients undergoing elective colectomy without complications, specifically comparing open and laparoscopic approaches.A multicenter prospective study was conducted across four public hospitals in Auckland and Christchurch, New Zealand. Consecutive adults undergoing elective colectomy were included over a 3-year period. Perioperative blood samples were collected and analysed for the following inflammatory markers: IL-6, IL-1β, TNFα, IL-10, CRP, leucocyte and neutrophil count. Statistical analysis was performed using SPSS statistical software.A total of 168 colectomy patients without complications were included in the analysis. Patients that underwent laparoscopy had significantly reduced IL-6, neutrophils and CRP on postoperative day (POD) 1 (p 0.05) compared to an open approach. IL-10 and TNFα were significantly reduced on POD 2 (p 0.05) in laparoscopic patients. Patients with a Body Mass Index (BMI) greater than 30 kg/mThe postoperative inflammatory response is influenced by surgical approach, perioperative medications, and patient factors. These findings have important implications in the utility of biomarkers in the diagnosis of postoperative surgical complications, in particular in the early diagnosis of anastomotic leak.

Published
2022

100. Sex Differences Among Patients Receiving Edoxaban vs Vitamin K Antagonist for Atrial Fibrillation After TAVR

Author

Roxana Mehran, Alessandro Spirito, James Jin, Cathy Chen, Julia Seeger, Julia Mascherbauer, Pascal Vranckx, Raul Moreno, Irene M. Lang, Anil Duggal, Yusuke Watanabe, Piera Capranzano, Annapoorna S. Kini, Verena Veulemans, Elena Tessitore, Kentaro Hayashida, Martin Unverdorben, Nicolas M. Van Mieghem, Christian Hengstenberg, and George D. Dangas

Published
2023
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