New Members

07/03/2024, Lucerne University of Applied Sciences and Arts, Luzern, Switzerland

07/03/2024, Hassan first University , Settat, Morocco

07/03/2024, Hochschule Luzern T&A, Horw, Switzerland

07/03/2024, Università Politecnica delle Marche, Ancona AN, Italy

01/29/2024, National Taiwan University of Science and Technology, Taipei City, Taiwan

10/17/2023, University of Toronto , Mississauga Ontario , Canada

7/27/2023, University Toledo, Toledo, USA

4/5/2023, ZheJiang Normal University, Zhejiang Province, China

04/11/2023, University of Nebraska at Omaha, Omaha, USA

01/17/2023, University of Limerick, Limerick, Ireland

09/13/2023, Universidad del Rosario, Bogonta , Colombia

08/22/2023, BioCardia, Sunny Val, USA Bringing personalized medicine to cell therapy for heart disease

06/27/2022, Punjabi University Patiala, Punjab, India

06/01/2022, Kestra Medical Technologies, Inc., Kirkland, USA Kestra Medical Technologies is a wearable medical device and digital healthcare company that protects patients with diagnostic and therapeutic technologies that are intuitive, intelligent, and mobile.

06/07/2021, University of Valladolid, Valladolid, Spain

04/30/2021, ETH Zurich, Zürich, Switzerland

04/30/2021, University Carlos III Madrid Lopez, Madrid, Spain

04/30/2021, Shahid Rajaee Teacher Training University, Tehran Province, Iran

01/12/2021, The National Academy of Sciences of Ukraine, Kyiv, Ukraine

01/12/2021, Universidad Rey Juan Carlos, Madrid, Spain

01/12/2021, Universidad iberoamericana, Mexico City, MEXICO

01/12/2021, Clinical Technology , Brecksville, USA

06/05/2020, Universitat Pompeu Fabra, Barcelona, Spain

06/05/2020, SUNY Upstate Medical University, Syracuse, USA

05/28/2020, University of Kent, Canterbury, United Kingdom

05/28/2020, The University of AIZU, Fukushima, Japan

05/28/2020, National Taiwan University, Taipei City, Taiwan

02/28/2020, Indian Institute of Space & Science & Tech, Kerala, India To be a world class educational and research institution contributing significantly to the Space endeavours

02/20/2020, Monash University, Melbourne, Australia Monash University is one of Australia’s leading universities and ranks among the world’s top 100. We help change lives through research and education.

12/24/2019, Universidad Politécnica de Madrid, Madrid, SPAIN

11/11/2019, University of Verona, Verona, ITALY

11/11/2019, University of Pittsburgh, Pittsburgh, USA The University of Pittsburgh is a state-related research university, founded as the Pittsburgh Academy in 1787. Pitt is a member of the Association of American Universities (AAU), which comprises 62 preeminent doctorate-granting research institutions in North America.

11/11/2019, Tianjin University of Technology, Tianjin , CHINA Tianjin University is the oldest institution of higher education in the modern history of China. Founded in 1895 as Peiyang University, Tianjin University’s 123-year history is the epitome of the progress of modern Chinese higher education, embodying the Chinese people’s indomitability through challenging times.

11/01/2019, Parsons Government Service, HOUSTON, USA Founded in 1944, Parsons Corporation --- a digitally enabled solutions provider --- is focused on the defense, intelligence, and critical infrastructure markets.

10/31/2019, University of Liverpool, Liverpool, UK

10/31/2019, Air University Islamabad, Islamabad, Pakistan The mission of Air University is to achieve excellence in teaching and research for producing graduates with sound professional knowledge, integrity of character, a keen sense of social responsibility and a passion for lifelong learning. The University shall stand committed to creating an environment conducive for attracting the best students, faculty and supporting staff for contributing to the development of a prosperous, peaceful and enlightened society.

05/15/2019, University of Wisconsin, Madison, USA For 168 years, this campus has been a catalyst for the extraordinary. As a public land-grant university and prolific research institution, our students, staff, and faculty members partake in a world-class education and solve real-world problems

05/15/2019, Utrecht University, Utrecht, NETHERLANDS

05/15/2019, University of Michigan, Ann Arbor, USA

05/15/2019, University of California Los Angeles, os Angeles, USA

05/15/2019, University of California Irvine, Irvine, USA Founded in 1965, UCI is the youngest member of the prestigious Association of American Universities. The campus has produced three Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Howard Gillman, UCI has more than 36,000 students and offers 222 degree programs.

05/15/2019, Technion , Haifa, ISRAEL A science and technology research university, among the world’s top ten,

05/15/2019, Tampere University of Technology, Tampere, FINLAND Tampere University is one of the most multidisciplinary universities in Finland. Almost all internationally recognised fields of study are represented at our university.

05/15/2019, Shenzhen Institute of Advanced Technology, Shenzhen, CHINA

05/15/2019, Shanghai Jiao Tong University, Shanghai, CHINA

05/15/2019, Saint Petersburg Electrotechnical University, Sankt-Peterburg, RUSSIA Saint Petersburg Electrotechnical University "LETI" is one of the world's largest education centers specializing in radio engineering, electrical engineering, electronics and computer science.

05/15/2019, Pontifical Xavierian University, Bogotá, Colombia

05/15/2019, University of Sfax , Sfax, TUNISIA

05/15/2019, King Saud University, Riyadh , SAUDIA ARABIA

05/15/2019, Khalifa University, Abu Dhabi, UNITED ARAB EMIRATES The newly-established Khalifa University of Science and Technology (KU) combines the Masdar Institute of Science and Technology (MI), the Khalifa University of Science, Technology and Research (KUSTAR) and the Petroleum Institute (PI) into one world-class, research-intensive institution, seamlessly integrating research and education to produce world leaders and critical thinkers in applied science and engineering.

05/15/2019, Argentine Institute of Mathematics, Buenos Aires , ARGENTINA

05/15/2019, INESC TEC, Porto, PORTUGAL INESC TEC is a private non-profit research institution, dedicated to scientific research and technological development, technology transfer, advanced consulting and training, and pre-incubation of new technology-based companies.

05/15/2019, Fraunhofer HHI, Berlin, GERMANY Innovations for the digital society of the future are the focus of research and development work at the Fraunhofer Heinrich Hertz Institute HHI. In this area, Fraunhofer HHI is a world leader in the development of mobile and optical communication networks and systems, fiber optical sensor systems as well as the processing and coding of video signals.

05/15/2019, Heart Input Output, Inc., Pittsburgh, USA

05/15/2019, Harrisburg University, Harrisburg, USA

05/15/2019, Warsaw University of Technology, Warsaw, POLAND

05/15/2019, Carlos III University of Madrid , Madrid, SPAIN UC3M´s mission is to contribute to the improvement of society through teaching of the highest quality and cutting-edge research in line with stringent international guidelines. The University aspires to excellence in all its activities, with the aim of becoming one of the top universities in Europe.

05/15/2019, Beth Israel Deaconess Medical Center, Boston, USA BIDMC is part of Beth Israel Lahey Health, a new health care system that brings together academic medical centers and teaching hospitals, community and specialty hospitals, more than 4,000 physicians and 35,000 employees in a shared mission to expand access to great care and advance the science and practice of medicine through groundbreaking research and education.

[01/24/2018], Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary The BRC is an outstanding institution of the internationally acknowledged Hungarian biological research. The Biological Research Centre was founded in 1971. The 4 institutes of BRC - the Institutes of Biophysics, Biochemistry, Genetics and Plant Biology - employ about 260 scientists whose work is hall-marked by highly appreciated international scientific publications and patents. The research topics include several fields of molecular and cell biology from the industrial utilization of bacteria through controlled improvement of cultivated plants to the problems of human health and environmental protection. BRC is mainly a scientific basic research centre, but scientists of BRC play an initiative role in the foundation and promotion of biotechnological companies, as well as in educational duties.

[01/02/2018], Universidade Federal do Maranhão, São Luís - MA, Brazil Founded in 1966, Universidade Federal do Maranhão (Federal University of Maranhão) is a non-profit public higher education institution located in the medium-sized city of São Luis (population range of 500,000-1,000,000 inhabitants), Maranhao. Officially accredited and/or recognized by the Ministério da Educação, Brazil (Ministry of Education, Brazil), Universidade Federal do Maranhão (UFMA) is a coeducational higher education institution. Universidade Federal do Maranhão (UFMA) offers courses and programs leading to officially recognized higher education degrees such as bachelor degrees in several areas of study.

[03/12/2018], University of Vigo, Viigo, Spain The University of Vigo is a modern and innovative institution, which offers more than 50 degree courses on three different campuses: a) the Vigo campus – which includes both the Lagoas Marcosende campus (15 km from the city centre) and the historical campus at Torrecedeira, b) the Ourense campus, and c) the Pontevedra campus. More than 24,000 students are registered at the three campuses, and 1,600 lecturers teach undergraduate and postgraduate programs at the University of Vigo. Our institution offers degrees in all knowledge areas, especially in the scientific-technological field. Some of the degrees are unique within the Galician university system and not very common in the rest of the Spanish universities: Fine Arts on the Pontevedra Campus, Mining and Telecommunication Engineering on the Vigo campus, and Tourism on the Ourense campus.

[01/24/2018], Stanford Medicine, Stanford, USA A leader in the biomedical revolution, Stanford Medicine has a long tradition of leadership in pioneering research, creative teaching protocols and effective clinical therapies. Our close proximity to the resources of the university — including the Schools of Business, Law, Humanities and Sciences, and Engineering, our seamless relationship with our affiliated adult and children’s hospitals, and our ongoing associations with the entrepreneurial endeavors of Silicon Valley, make us uniquely positioned to accelerate the pace at which new knowledge is translated into tangible health benefits.

[01/24/2018], The Austrian Research Institute for Artificial Intelligence, Vienna, Austria The Austrian Research Institute for Artificial Intelligence (OFAI) is one of Europe's leading non-profit contract research institutions. Services offered range from consultancy, basic and applied research on a contractual base, to working as partner or prime contractor in scientific projects on a national or European level, with a twenty year experience in a diversity of domains, from economic, engineering, administrative to social and cultural tasks.

[10/25/2017], University of Tennessee Health Science Center, Memphis, USA As the flagship statewide, public, academic health system, the mission of the University of Tennessee Health Science Center is to bring the benefits of the health sciences to the achievement and maintenance of human health, with a focus on the citizens of Tennessee and the region, by pursuing an integrated program of education, research, clinical care and public service. Employing more than 6,000 people on its faculty, staff and not-for-profit corporation faculty practice groups, UTHSC contributes more than $2.7 billion to the economy of Tennessee.

[10/24/2017], Dankook University, Yongin-si,, South Korea Dankook University cherishes truth and service as its guiding principles. It is our belief that the purpose of research and study lies beyond simply acquiring tools for sustenance – the ultimate purpose of higher learning is the enrichment of human knowledge and culture. Principally, scholars are obligated to return such knowledge to society and contribute to historical advancement. They must seek to develop sharp, critical minds and a righteous moral character; by doing so and voluntarily participating in the betterment of society as a whole, one embodies the path Dankook wishes to set forth. It has been the unwavering devotion towards realizing such duties of higher education and patriotism that has led to Dankook University’s existence in its current form

[09/28/2017], Chinese PLA General Hospital, Beijing, China The Chinese People’s Liberation Army (PLA) General Hospital is a large, modern, comprehensive teaching hospital providing high quality health care and opportunities for postgraduate medical education and scientific research. The hospital was founded in 1953, and is situated on the western part of the 4th Beijing Ring Road. The hospital has 165 clinical medical departments, which each year accept 49,000 outpatients and emergency patients while performing nearly 90,000 surgery cases. The medical- health care center is noted for providing high-end preventive care services.

[07/20/2017], University of Central Florida, Orlando, USA The Advanced Research Computing Center (ARCC) at the University of Central Florida houses high performance computing resources for use in research by faculty across campus. Research supported by the ARCC covers a variety of different disciplines, including Engineering, Modeling and Simulation, Optics, Nanoscience, and many others. The ARCC staff also pursues research in machine learning and visualization, as well as information technology. Currently, the center houses a high performance computing system known as Stokes, which is used to help support and drive research within the university.

[05/02/2017], Shandong University, , China Founded in 1901, Shandong University, based in Jinan, China, is the nation’s largest public university. It has prepared over 400,000 individuals in a variety of specialties, and has been making significant contributions to the country’s economic and social development. The growth of the university has allowed it to rise to the forefront of many fields in China. They continually develop new disciplines such as crystal materials, cardiovascular functional recovery, and new drug manufacturing to stay on the cutting edge of scientific research. Many of these newly formed disciplines have quickly risen to the first-class level within the country, and some are even know abroad.

[02/17/2017], University of Porto, Praça de Gomes Teixeira, Portugal The University of Porto, founded in 1911, is a leading scientific and research institution located in Portugal. The university is internationally recognized for the quality of research it produces, and is consistently ranked among the 150 best European universities. It is an important driver of economic, social, and scientific development within Portugal, and strives to be a strong partner of the business community. By combining quality teaching with a focus on market needs, the university strives to actively participate in, and encourage, the progress of communities in which it operates.

[05/24/2016], Marche Polytech University, Ancona, Italy The Department of Life and Environmental Sciences was established in 2011 by merging a number of laboratories involved in a wide spectrum of fundamental and applied research topics. The department is a center of excellence of the Università Politecnica delle Marche and includes more than 100 scientists and technicians that conduct research in areas such as analytical and organic chemistry, biophysics, cellular and molecular biology, biochemistry and genetics, microbiology and biotechnology, viral, prokaryotic, fungal, algal, plant and animal systematics, physiology and reproduction, marine biology, ecology, eco-toxicology, oceanography, Earth sciences, risk reduction and civil protection.

[05/12/2016], University of Buenos Aires, Buenos Aires, Argentina Buenos Aires University consists of thirteen colleges/schools, dozens of research institutes, and two secondary schools, offering more than 100 undergraduate majors. There is a teaching staff of 30,000 teachers, and approximately 300,000 students; 30% of scientific research in Argentina takes place at UBA. Standard undergraduate studies last approximately 5 years. Buenos Aires University offers several graduate programmers, masters, PhDs, and specialization courses as well.

[05/12/2016], Queen's University, Kingston, Canada The mission of Queen's University has been articulated in a number of different forms and formats over the past decade. In all of the presentations, the key elements have remained constant: The University will build on the strength that is Queen's - students, faculty, staff and alumni - to be among the best of internationally known universities in Canada, recognized for: •the exceptional quality of undergraduate and graduate students and programs in the arts, sciences and professions; •the intellectual power and value of research and scholarship by faculty members and students; •the exemplary service of the University and that of its graduates to the community and the nation and the community of nations.

[04/28/2016], University of Leuven, Leuven, Belgium KU Leuven is a research-intensive, internationally oriented university that carries out both fundamental and applied research. It is strongly inter- and multidisciplinary in focus and strives for international excellence. To this end, KU Leuven works together actively with its research partners at home and abroad.KU Leuven encourages personal initiative and critical reflection in a culture of idea exchange, cooperation, solidarity and academic freedom.

[03/07/2016], Mayo Clinic, Rochester, USA Mayo Clinic is the first and largest integrated nonprofit medical group practice in the world, employing more than 3,800 physicians and scientists, as well as 50,900 allied health staff. Based out of Rochester, MN, the Mayo Clinic’s mission is “to inspire hope and contribute to health and well-being by providing the best care to every patient through integrated clinical practice, education, and research.” The practice specializes in treating difficult cases through tertiary care, and spends over $500 million a year on research. It was also recognized as one of the best hospitals in the U.S. for 2015-2016 by U.S. News & World Report.

[03/02/2016], Czech Technical University, Prague, Czech Republic The Czech Technical University in Prague (CTU) is an internationally recognized higher education and research institution with more than 300 years of tradition and excellence. CTU is a leading technical research university with a large focus on cutting edge science and engineering, paired with a high-quality technical education. With 8 departments each focused on an engineering specialty, the university educates modern specialists, scientists, and managers who are dynamic, flexible, and able to rapidly adapt to the requirements of the market.

[02/10/2016], CERB, Baugy, France Located in Baugy, France, CERB was founded in 1973 and has developed into a leading international contract research organization (CRO) in the fields of pre-clinical pharmacology and toxicology. Taking on the challenges of modern drug development, CERB has created a distinctive image as a leading major service provider to the pharmaceutical industry in the context of innovative bio-medical research. CERB takes advantage of its sophisticated synergy between pharmacology and toxicology resources to provide complete pre-phase I packages for new molecules in an economic and timely manner

[01/07/2016], Goergen Institute for Data Science (GIDS), Rochester, USA The GIDS supports faculty research, particularly collaborative public-private research partnerships spanning several domains, such as developing health care breakthroughs, improving our knowledge of how the brain works, and creating tools and systems to efficiently use data. The GIDS is working to build strategic alliances and business partnerships among the academic, government, and business communities, leveraging University of Rochester expertise.

[10/06/2015], Dresden University of Technology, Dresden, Germany Dresden University of Technology is one of eleven German universities that were identified as an “excellent university", and includes over 37,000 students with 14 institutions offering a wide range of academic programs. The Institute of Biomedical Engineering focuses on the early detection, diagnosis, and treatment of life-threatening cardiovascular disease. With a strong focus on research.

[10/06/2015], Biomedical Systems, Maryland Heights, USA Biomedical Systems has set the health care industry standard by providing innovative approaches to non-invasive diagnostic services, clinical trials, and products. They provide their clients with the ability to increase cost efficiencies and bring studies to database lock on an advanced timeline by combining over 20 modalities in one study. Biomedical Systems' pioneering spirit is based on a strong history as a privately held company that focuses on clients and people.

[09/15/2015], VivaQuant LLC, Shoreview, USA VivaQuant provides products, services and technology that incorporate advanced signal processing to more accurately extract valuable information from biological signals. Through their technology they are committed to improving the lives of patients and the productivity of clinicians and researchers.

[08/04/2015], Sensium Healthcare Ltd, Abingdon, UK Sensium Healthcare, A global pioneer in wireless monitoring of vital signs. The company focus is on ultra-low power, lightweight, monitoring solutions which improve patient care and safety,shorten hospital stays and reduce healthcare costs.

[07/28/2015], Seoul National University, , South Korea, Seoul National University, As Korea leading research university, honoring the ideals of a liberal education aim at teaching students a lifelong love of learning that will form the basis for continuous personal growth. It includes 16 Colleges, 1 Graduate School, 9 Professional Graduate Schools with 16,006 Undergrad Students, 10,559 Graduate Students.

[07/16/2015], Boston Scientific, Marlborough, MA, USA A leading innovator of medical solutions that improve the health of patients around the world. Products and technologies used to diagnose or treat a wide range of medical conditions, including heart, digestive, pulmonary, vascular, urological, women health and chronic pain conditions. Boston Scientific is dedicated to transforming lives through innovative medical solutions that improve the health of patients around the world.

[09/30/2014], Harvard Medical School-Wyss Institute for Biologically Inspired Engineering, Boston, USA The Wyss Institute aims to discover the engineering principles that Nature uses to build living things, and harnesses these insights to create biologically inspired materials and devices that will revolutionize healthcare and create a more sustainable world. In medicine, the Institute is developing innovative materials, devices, and disease reprogramming technologies.

[03/12/2014], University Medicine Berlin, Berlin, Germany The Charite is one of the largest university hospitals in Europe. Here, 3700 doctors and scientists heal, do research and teach at the top international level. More than half of the German Nobel Prize winners in medicine and physiology come from the Charite, among them Emil von Behring, Robert Koch and Paul Ehrlich.

[01/23/2014], BioSign GmbH, Ottenhofen, Germany Developing innovative measurement and therapy systems for professionals and end-users in the subject area vegetative (autonomic) nervous system. BioSign is responding to the growing medical recognition that disturbances in the autonomic nervous system and disturbances in the interplay of the various organs are involved with the autonomic nervous system.

[11/14/2013], University of Rochester, Computer and Electrical Engineering, Rochester, USA This department has multiple programs related to energy, to health and medicine, to the connected world, and to music. Specific research programs span a wide range, including medical imaging, image processing, genomics, audio and music signal processing, among others.

[10/31/2013], RIT, Microsystem Engineering, Rochester, USA The multidisciplinary program builds on the fundamentals of traditional engineering and science including the manipulation of electrical, photonic, optical, mechanical, chemical, and biological functionality to process, sense, and interface with the world at a nanometer scale.

[09/10/2013], Medtronic, Inc., Medtronic , USA Medtronic develops and manufactures innovative medical device technology and therapies to treat chronic disease worldwide.

[06/11/2013], RIT, Department of Biomedical Engineering, Rochester, USA The RIT mission is to provide technology-based educational programs for personal and professional development. We rigorously pursue new and emerging career areas. We develop and deliver curricula and advance scholarship relevant to emerging technologies and social conditions. Our community is committed to diversity and student centeredness and is distinguished by our innovative and collaborative spirit.

[05/02/2013], Masonic Medical Research Laboratory, Utica, USA The Masonic Medical Research Laboratory is a not-for-profit institute dedicated to improving the health and quality of life for all. The Laboratory primary mission is to conduct high quality basic and clinical research aimed at generating knowledge and information necessary for development of the medical cures and treatments of tomorrow.

[04/22/2013], Universitat Politecnica de Catalunya (Barcelona-Tech), Barcelona, Spain. The Universitat Politecnica de Catalunya (UPC): BarcelonaTech is a public institution dedicated to higher education and research, specialised in the fields of engineering, architecture and science. With a focus on intellectual rigor, critical thinking, a transversal approach to knowledge, educational innovation and entrepreneurship, the UPC produces competent professionals with the skills they need to tackle present and future challenges.

[03/20/2013], Teschnische Universitat(TU), Berlin, Germany The TU Dresden is one of eleven German universities that were identified as an Excellence University. TUD has about 36.500 students and almost 5319 employees, 507 professors among them, and, thus, is the largest university in Saxony.

[02/08/2013], Baskir State Pedagogical University (BSPU), Uta, Russia M. Akmullah BSPU is a large scientific, educational, cultural and social center of the Republic of Bashkortostan. It includes the Institute of Pedagogics, the Institute of Professional Education and Information Technologies, the Institute of Historical and Legal Education, the Institute of Philological Education and Cross-Cultural Communication and 7 departments with about 12 000 students.

[02/01/2013], Chung-Yuan Christian University, Taiwan, China Chung Yuan Christian University is founded on the spirit of Christian love for the world. With faith, hope, and love, we endeavor to promote higher education for the benefit of the Chinese people, aiming at the pursuit and advancement of genuine knowledge in order to maintain our cultural heritage and, thus, to serve humankind.

[12/11/2012], Cardio-QT Ltd., Glasgow, UK Headed by Royal College Accredited Cardiologist and Bioengineer supported by PhD Scientists, Cardio-QT Ltd is an award winning, highly innovative Core Cardiac Analysis Laboratory offering an array of sophisticated validated techniques to solve all analytical research problems.

[10/21/2012], National Polytechnic Institute of Mexico, Santiago de Querétaro, Mexico The Institute is the State secular free education institution, guide of public technological education in Mexico. A leader in the generation, application, dissemination and transfer of scientific and technological knowledge.

[09/24/2012], Massachusetts General Hospital, Harvard Medical School, Boston, USA Mass General has long been a leader in successfully bridging innovative science with state-of-the-art clinical medicine. With an annual research budget of nearly $764 million, Mass General conducts the largest hospital-based research program in the United States - a program that spans more than 20 clinical departments and centers across the hospital. This funding drives discoveries and breakthroughs in basic and clinical research, which translate into new and better treatments that transform medical practice and patient care.

[05/24/2012], College of Veterinary Medicine, Cornell University, Ithaca, USA The mission of the Department of Biomedical Sciences is to educate and inform the veterinary and human biomedical communities through our diverse research and clinical service excellence as well as through our commitment to undergraduate, graduate, and veterinary teaching.

[05/02/2012], The Victor Chang Cardiac Research Institute (VCCRI), Darlinghurst NSW 2010, Australia The VCCRI is committed to excellence in research into heart disease and cardiovascular biology, cardiovascular research training, and facilitating the rapid application of research discoveries to patient care.

[02/09/2012], SAIT, Samsung Advanced Institute of Technology, Gyeonggi-do, Korea SAIT provides a full spectrum of support so its researchers can focus on creative research, seek the convergence of heterogeneous technologies and take up new challenges. Meanwhile, SAIT also actively engages in "open innovation" to jointly create future value with other research institutions through collaboration.

[01/26/2012], FDA-CDRH: Center for Devices and Radiological Health, Silver Spring, USA FDA Center for Devices and Radiological Health (CDRH) is responsible for regulating firms who manufacture, repackage, relabel, and/or import medical devices sold in the United States. In addition, CDRH regulates radiation-emitting electronic products (medical and non-medical) such as lasers, x-ray systems, ultrasound equipment, microwave ovens and color televisions.

[01/10/2012], Department of Physiological Nursing, University of California, San Francisco, USA The Mission of the Department of Physiological Nursing prevention of UCSF is to study the prevention, measurement, and treatment of physiological and biobehavioral responses to health, illness/disease and aging. Psycho-physiological interrelationships and interventions also are studied. Research spans all phases of the health/illness trajectory including people who are healthy, critically ill, living with a chronic illness, and those at the end of life.

[01/03/2012], University of Bologna (HST-ICIR), Bologna BO, Italy The University of Bologna was probably the first University in the western world. Its history is one of great thinkers in science and the humanities, making it an indispensable point of reference in the panorama of European culture. Bologna has thus been called upon to forge relationships with institutions in the most advanced countries to modernise and expand its activity. Among the many challenges which it has met with success, Bologna committed itself to the European dimension which has now led to adoption of the new university system.

PRESS CENTER

[09/23/2010]: AstraZeneca joins the THEW to further cardiac safety inThe Medical News: here .

[12/16/2009]: The Director of the THEW interviewed by Technology Review published by the MIT: here .

[11/11/2009]: New Research Center to Focus on Cardiac Safety and Innovation in Pharmaceutical Industry Today: here .

[6/11/2009]: University of of Rochester and FDA Partner for ECG Database, Drug Discovery & Development Magazine. More info here

[5/6/2009] FDA website Existing Partnerships FDAs Public-Private Partnership Program: THEW

[03/28/2009] Public and Private part- nership to help determine Clinical Biomarker Utility in Applied Clinical Trials online.com. >here

Newsletter Issue 9, July 2010

QT evaluation for drugs with autonomic effects & other Scientific activities

thewNews

 


QT/QTc Evaluation for Drugs with Autonomic Effects (part I)

by JP. Couderc, PhD

The incidence of torsades de pointes following the administration of antipsychotic and other CNS drugs remains unknown but the risk of sudden cardiac death is estimated to be 15/10,000 persons per year. In thorough QT studies, the potential interaction between drug effect on the ANS and the QT interval may lead to biased estimate of QT effect, and wrong designation of a drug as a QT prolonger. Consequently, QT assessment methods specifically designed to address the issue of heart rate effect on QT need to be considered. This was pointed out by FDA regulators at many occasions including Dr. Christine Garnett (FDA/CDER) during the THEW Cardiac Safety Meeting in Silver Spring, MD, this past year ( slides available for download here ). Dr. Garnett emphasized the need for looking at continuous ECG information either through telemetric or Holter recordings. Today, the methods evaluated by the Agency are: individual correction (QTci), RR bin and QT beat-to-beat methods. Two of these methods are presented in depth in this newsletter by their respective inventors. The QTci and associated QT/RR modeling technologies will be presented thoroughly in the next release of this Newsletter.

Interestingly, the RR binning and QT beat-to-beat methods are increasingly used in thorough QT studies involving drugs with an autonomic effect. Drs. Badilini and Fossa describe with great expertise these methods in the next sections of this newsletter. These articles are available (full versions) in the Expert Opinion section of the THEW website ( here ) . In parallel, the FDA/CDER released an offer for a 2-year fellowship at the FDA campus to ensure that the Agency is ready to receive results from such methodologies (large set of measurements from continuous ECG recordings). A copy of the fellowship postion is available here .

Also in this Newsletter, this first semester of 2010 marks the first set of scientific presentations based on data from the THEW. As announced in our previous Newsletter, we confirm that the program of the next Computing in Cardiology Meeting to be held in Belfast (UK) this September will include a session dedicated to the works developed exclusively using the data from the THEW. The Agenda for this session entitled "QT and Cardiac Repolarization" was designed by the organizers as follow:

  1. Analyzing Thorough QT Study 1 & 2 in the Telemetric and Holter ECG 
    Warehouse (THEW) Using Hannover ECG system (HES®): A validation 
    study Antoun Khawaja*, Ratko Petrovic, Anton Safer, Tobias Baas, Olaf Doessel and  Ronald Fischer.
  2. Torsadogenic Drug-Induced Increased Short-term Variability of JT-area
    Xiao Jie*, Blanca Rodriguez and Esther Pueyo
  3. Electrocardiographic Markers Associated with Sotalol-induced Torsades 
    de Pointes Jean-Philippe Couderc*, Xiaojuan Xia, Stefan Kaab and Wojciech Zareba
  4. Comparison of Three T-end Delineation Algorithms Based on Wavelet 
    Filterbank, Correlation and PCA Tobias Baas*, Franz Gravenhorst, Ronald Fischer, Antoun Khawaja and Olaf  Dössel
  5. QT/RR Coupling and Gender Differences. Josef Halamek*, Pavel Jurak, Jolana Lipoldova and Pavel Leinveber
  6. Modified Rectangular Finite Impulse Response Filter for Stabilization of QT 
    Measurement. Jing Wu, Jean-Philippe Couderc* and Xiaojuan Xia

In addition, the works from students whom have taken the THEW training program this past December will be presented in various poster session as well:

  1. A Comparison of IIR and Wavelet Filtering for Noise Reduction of the ECG
    Jens Stampe Soerensen*, Lars Johannesen, Ulrik Silvanus Lerkevang Grove, 
    Kasper Lundhus, Jean-Philippe Couderc and Claus Graff
  2. Analysis of Heart Rate Adaptation in Long-Term ECG Recordings Using 
    RR-Binning Lars Johannesen*, Ulrik Silvanus Lerkevang Grove, Jens Stampe Soerensen, Mick  Lykkegaard Schmidt, Claus Graff and Jean-Philippe Couderc
  3. Wavelet-based Algorithm for Delineation and Classification of ECG Waves
    Lars Johannesen*, Ulrik Silvanus Lerkevang Grove, Jens Stampe Soerensen, Mick  Lykkegaard Schmidt, Jean-Philippe Couderc and Claus Graff

These works represent the first scientific publications from various private and public organization members of our initiative. We would like to congratulate these scientists and students for the interesting research work they have generated based on the data from the THEW repository. We hope that the new database we have added this month (described in details below) which contain Holter recordings from more than 1,150 of chest pain patients from the IMMEDIATE AIM study will spawn additional research works from our members.

 


The dynamic beat-to-beat method by Anthony Fossa, PhD

The dynamic QT beat-to-beat (QTbtb) analysis has been reported to differentiate changes of QT interval duration due to heart rate or autonomic state from impaired repolarization.  This work has recently been reviewed with both clinical [1] and preclinical translational data [2,3]. The method utilizes all individual cardiac cycles from continuously collected ECG telemetric or Holter data to define the normal baseline which contains different autonomic states experienced over 24-hours. The baseline QT-RR boundaries therefore also contain beats incurred during all normal hysteresis (defined as the lag in QT interval adaptation for changes in RR interval), sinus arrhythmia and QT-RR variability during activities such as eating, sleeping and ambulatory movements. The upper confidence bound for the baseline of all beat-to-beat QT interval values is defined across the entire 24-hr RR interval range and beats exceeding this limit are flagged as outlier beats for further arrhythmia vulnerability assessment.  These beats would be assumed to possess potential risk of arrhythmia and can be further analyzed by quantifying the temporal heterogeneity or assessment of ECG restitution of the entire dataset (described below). 
Using the individual 24-hr pre-dose data as a baseline for all subsequent analyses ( Figure 1 , panel A), the effect of a drug, placebo and baseline-adjusted placebo corrected value can be readily assessed.    For any specific time point or timeframe, all continuously collected viable beats are analyzed with rigorous automated quality control procedures.  This is usually a 5 minutes period during drug administration and its time-matched placebo ( Figure 1 , panel B). The center of this 5-min cloud of data or centroid is calculated as the median QT and the median RR interval ( Figure 1 , panel C). This median QT value (QTbtb) value for any nominal time point is compared to the centroid of all beats extracted within a similar RR interval range (e.g. ± 12 ms) from the 24-hr baseline dataset to provide a delta-QTbtb value ( Figure 1 , Panels D, E and F). 

FIGURE 1

b2b

The beats used to calculate the delta-QTbtb for the nominal time points can also be used for calculating the corrected QTcB or QTcF values for simultaneous comparison ( Figure 2 ). The same procedure used to define the delta-QTbtb value for placebo can then be applied for the on-drug treatment nominal time points. The placebo-adjusted time-matched values (delta-delta QTbtb) are simply calculated by subtraction of the time-matched placebo values from the same time-matched values on treatment from the same subject. However, one advantage of using continuous ECG collection with beat-to-beat analyses is that entire timeframes of data when on-drug can be compared to off-drug periods to quickly determine whether an effect is present by the outlier methods described below ( Figure 2 , panel D). 
An essential component of the beat-to-beat method is to determine whether repolarization is significantly impaired beyond normal autonomic boundaries by applying quantile regression techniques to define the upper 97.5% reference boundary of QT over RR intervals from the normal 24-hr data (See Figure 2 from baseline day of the study).

FIGURE 2:

b2b2

An outlier analyses examines the percentage of beats that exceed the upper 97.5% reference boundary of the baseline data during any period.  By definition, for a drug with no effect this percentage should be around 2.5 % of beats exceeding the upper boundary. The % outliers values can be handled as described above for QTbtb values and thus a time-matched placebo adjusted value can be obtained for each time point.  A lower 90% two-sided confidence interval can be determined for the mean of the % outlier values at any time point to determine whether there is a statistically significant increase in outliers.  As mentioned above, this same type of analysis can also be conducted for any period of time that the drug is used, including the entire time at efficacious concentrations to readily ascertain the net effect of drug vs. normal QT/RR relationship.
Arrhythmia liability due to changes in temporal heterogeneity of outlier beats can be assessed by a bootstrap analysis applied only to beats that exceed the upper 97.5% reference bound.  The median value during any time period on-drug is determined to ascertain whether these beats are of greater magnitude in general compared to beats normally exceeding the upper 97.5% reference bound of QT intervals off-drug.  Bootstrapping provides confidence intervals of the median value.  The width of the confidence intervals is used as a measure of heterogeneity of the QT interval outlier beats, which has been associated with increased arrhythmia liability and can be compared to the width of the confidence intervals at normal levels from the same individual when obtained off-drug.
A second procedure to evaluate arrhythmia liability of temporal dynamics is to evaluate the cardiac ECG restitution. Restitution is the ability of the heart to recover from one beat to the next.  This measures the QT interval (working phase of the heart) in relationship to the previous TQ interval (resting phase of the heart).  When the heart is not under stress, this ratio is less than 1, meaning the heart is resting more than it is working.  However, as stress increases on the heart, for example, during exercise, the heart works more than it rests, increasing this ratio to greater than 1. Sustained periods with inadequate recovery between beats would presumably lead to increased arrhythmia vulnerability as occurs in extreme cases with salvos of non-sustained ventricular tachycardia or an R on T phenomenon where TQ interval equals zero.  Arrhythmia liability not associated with QT prolongation may be more related to the TQ interval shortening or increase in the QT/TQ ratio of each beat.  When QT prolongation is present along with increase QT and RR variability or increased heart rate during proarrhythmic states, the QT/TQ ratio can increase dramatically for transient periods of time possibly leading to initiation of reentry. Thus in addition to the median QT interval, the median TQ interval and median QT/TQ ratio are assessed in ECG restitution. Other parameters to describe length of stress and magnitude of extreme changes are defined as % beats greater than 1 and upper 98% bounds for the QT/TQ ratio, respectively.

Reference for this article can be found here .


Holter RR Bin Analysis by Fabio Badilini, PhD

Holter bin is a method used to quantify changes of electrocardiographic metrics from continuous recordings. This technique was introduced to characterize repolarization patterns in healthy subjects (1) and it has been applied to study several pathological conditions (2,3) and for the assessment of drug-induced ECG changes (4), particularly in the presence of heart rate changes (5).
Holter bin is based on the concept of selective beat averaging. An exploring time window is initially defined; within this time window all the cardiac beats characterized by the same preceding heart-rate (or RR interval) are pooled and averaged to form a representative waveform for that specific RR interval (or RR bin). When the variable of interest is the QT interval, the rule of selection can be tailored to meet further conditions, as for example to take into account (or to compensate for) the effect of hysteresis: for example excluding all the cardiac beats not preceded by stable heart rate or, alternatively, using the hysteresis-corrected RR interval by a mathematical model as the bin-inclusion parameter.
Holter bin requires adequate signal processing; for example the precise position of each cardiac beat should be properly verified and automatically adjusted (trigger jitter correction); at need, the individual cardiac complexes may need to be re-interpolated to improve the respective alignment before averaging. The exploring window should be rigorously controlled: for example, diurnal and nocturnal periods and, more in general, regions with known modified autonomic tone (for example exercise periods) should not be mixed in the same Holter bin session. The ideal length of the exploring window depends on the specific experiment. In the case of pharmaceutical trials, a 2 to 4-hours window centered at peak concentration has been typically used (4).
Holter bin is particularly suited to inspect metrics that need to be compared in conditions or maneuvers that modify the hart rate, for examples when comparing the effect of repolarization on drugs that change the baseline RR interval (5). Rather than enforcing the application of one or more QT/RR models models, the approach assesses changes by comparing the study parameters (e.g. QT interval) belonging to the same RR-bin, i.e. enforcing a comparison at identical heart-rate, thus avoiding the application of correction formulae.The typical output of a Holter-bin analysis session is typically a set of comparisons associated with each of the RR bins inspected : for example (in the context of a QT study) the averaged and the maximum QT difference across all the RR bins could be reported. Within-bin variability is important and can be assessed by several indicators such as the bin "density" (i.e. number of cardiac beats pooled inside each bin) or the variability of some parameters the individual beats included into the bin (for example SD of the beat-to-beat QT intervals).

Pros

    1. No need to implement correction models
    2. Good to assess changes associated with moderate (up to 10 bpm) heart rate changes, where the degree of RR overlap between baseline or placebo and on-drug is significant.
    3. QT hysteresis can be easily controlled.

Cons:

    1. Within the exploring window cardiac beats are pooled according to the preceding heart rate and the time-scale is lost.
    2. Requires sophisticated beat-to-beat processing including appropriate quality control of automated ECG analyses

Reference for this article can be found here .


New database available in the THEW including 1,154 subjects from the Emergency Department for Chest pain: IMMEDIAT AIM study growth

The THEW has signed an agreement with University of California San Francisco for transferring the data from the IMMEDIATE AIM (Ischemia Monitoring and Mapping in the Emergency Department In Appropriate Triage and Evaluation of Acute Ischemic Myocardium) in to the THEW. This dataset includes digital ECG data recorded from 2001-2005 with Mason-Likar 12-lead Holter monitor devices (average length of recordings, 15.9 hours ± 9.0). The database includes 1154 subjects with 547 patients had a final diagnosis of acute coronary syndrome - ACS (105 with acute myocardial infarction; 178 with unstable angina), 607 with non-ACS cardiac diagnosis (e.g., heart failure, arrhythmia), and 271 had a non-cardiac diagnosis (e.g., gastrointestinal reflux disease). Demographic information, coronary risk factors, medical history and clinical data (serum troponin, cardiac catheterization, hospital length of stay and complications, transient ischemic events, and 1-year mortality) is available.

For more information please visit the database webpage here .

KC

THEW Team: Kelley Concannon-Cenname, Clinical Technologist

Kelley Concannon-Cenname is a native of Rochester, N.Y and is a graduate of Monroe Community College with an Associate Degree in Science.  Kelley came to the University of Rochester in 2008 and has 17 years of Cardiology experience. She is a Certified Electrocardiograph Technician, with expertise in rhythm interpretation.  While currently enrolled at the Isabella Graham Hart School of Nursing, her primary roles in the THEW organization will be preparing and annotating Holter ECGs.