Multidisciplinary Clinical Research Research Articles

Statistical challenges and solutions in multidisciplinary clinical research: Bridging the gap between

This paper delves into the intricate challenges and innovative solutions in applying statistical methodologies within clinical research, aiming to bridge the gap between biostatistics and medicine. The study meticulously examines fundamental biostatistical concepts, addressing the complexities of modern clinical trials and observational studies. Through a comprehensive review of advanced regression models, causal inference techniques, and machine learning algorithms, the paper illuminates the evolving landscape of biostatistics in handling high-dimensional data and confounding variables. The methods employed in this study involve an extensive analysis of current literature, case studies, and practical applications that demonstrate the utility of these advanced methodologies. Key findings reveal that traditional statistical approaches often fall short in capturing the complexities of clinical data, necessitating the adoption of more sophisticated techniques. The integration of non-linear regression models, robust causal inference methods, and machine learning has significantly enhanced the accuracy and reliability of research outcomes, offering deeper insights into patient outcomes and treatment efficacy. Conclusions drawn from this study underscore the critical need for a paradigm shift in clinical research, moving beyond the rigid reliance on p-values towards a more holistic approach that emphasizes effect sizes, confidence intervals, and practical significance. The paper recommends continued innovation in statistical methodologies, particularly the integration of big data analytics and machine learning, to address the growing complexities of biomedical data. Furthermore, it advocates for interdisciplinary collaboration and ethical considerations in the application of these advanced techniques to ensure that biostatistics continues to contribute meaningfully to the advancement of medical science.

Integrating frontiers: a holistic, quantum and evolutionary approach to conquering cancer through systems biology and multidisciplinary synergy.

Cancer therapy is facing increasingly significant challenges, marked by a wide range of techniques and research efforts centered around somatic mutations, precision oncology, and the vast amount of big data. Despite this abundance of information, the quest to cure cancer often seems more elusive, with the "war on cancer" yet to deliver a definitive victory. A particularly pressing issue is the development of tumor treatment resistance, highlighting the urgent need for innovative approaches. Evolutionary, Quantum Biology and System Biology offer a promising framework for advancing experimental cancer research. By integrating theoretical studies, translational methods, and flexible multidisciplinary clinical research, there's potential to enhance current treatment strategies and improve outcomes for cancer patients. Establishing stronger links between evolutionary, quantum, entropy and chaos principles and oncology could lead to more effective treatments that leverage an understanding of the tumor's evolutionary dynamics, paving the way for novel methods to control and mitigate cancer. Achieving these objectives necessitates a commitment to multidisciplinary and interprofessional collaboration at the heart of both research and clinical endeavors in oncology. This entails dismantling silos between disciplines, encouraging open communication and data sharing, and integrating diverse viewpoints and expertise from the outset of research projects. Being receptive to new scientific discoveries and responsive to how patients react to treatments is also crucial. Such strategies are key to keeping the field of oncology at the forefront of effective cancer management, ensuring patients receive the most personalized and effective care. Ultimately, this approach aims to push the boundaries of cancer understanding, treating it as a manageable chronic condition, aiming to extend life expectancy and enhance patient quality of life.

FAPI PET/CT Imaging—An Updated Review

Despite revolutionizing the field of oncological imaging, Positron Emission Tomography (PET) with [18F]Fluorodeoxyglucose (FDG) as its workhorse is limited by a lack of specificity and low sensitivity in certain tumor subtypes. Fibroblast activation protein (FAP), a type II transmembrane glycoprotein, is expressed by cancer-associated fibroblasts (CAFs) that form a major component of the tumor stroma. FAP holds the promise to be a pan-cancer target, owing to its selective over-expression in a vast majority of neoplasms, particularly epithelial cancers. Several radiolabeled FAP inhibitors (FAPI) have been developed for molecular imaging and potential theranostic applications. Preliminary data on FAPI PET/CT remains encouraging, with extensive multi-disciplinary clinical research currently underway. This review summarizes the existing literature on FAPI PET/CT imaging with an emphasis on diagnostic applications, comparison with FDG, pitfalls, and future directions.

Development, maintenance and regulation of multidisciplinary research teams to improve clinical research quality in India - implications for HR practice

The overall quality of the clinical research is low in India and there are number of social determinants of health, cultural, institutional, fiscal, financial plus technological factors that affects the performance and management of clinical researchers. The study focuses to understand the important effects of the multidisciplinary clinical research teams and human resource management on the outcomes of the clinical research. The study uses systematic review and thematic analysis as the methodology in order to understand the research problem in detail and provide solutions to the clinical research problems in the country. A total of scholarly 21 articles has been systematically reviewed and four major themes has been found out. The study finds out multiple complex factors that ranges from technical, professional, personal, social, cultural dimensions to institutional and organizational types that needs to be addressed, in order to improve the quality of clinical and medical research in the country. The translational and the implementation sciences has been found to play a critical role in clinical research and the academic-industry collaborations is necessary too. The human resource management plays a cardinal role in the whole undertaken of the clinical research process that has been explained in the research study. The implications of the human resource management and the clinical research management has been mentioned as well, that is to be considered very closely.

China guideline for the screening and early detection of female breast cancer(2021, Beijing)

Breast cancer is the commonest malignant tumor among Chinese females, ranking first in terms of incidence of female cancers. Commissioned by the Disease Prevention and Control Bureau of National Health Commission of the People's Republic of China, the National Cancer Center formulated the Guideline for Screening and Early Diagnosis and Treatment of Female Breast Cancer in China according to WHO Handbook for Guideline Development. The methods on Cochrane China were referred to for the formulation of the system evaluation procedures. The GRADE methods for assessment, formulation and evaluation were adopted for the classification of evidence quality and recommendation strength, and the items were reported according to Reporting Items for Practice Guidelines in Healthcare. Based on the results of evaluation, the guideline gives evidence-based recommendations for the appropriate population and technical procedures for breast cancer screening and early diagnosis and treatment after comprehensive consideration of China's national conditions, the advantages and disadvantages of the evidence, the quality of the evidence, the economic cost of screening, the feedback of multidisciplinary clinical research respondents, and in-person expert consensus. It is aimed at regulating the practices of female breast cancer screening and early diagnosis and treatment and enhancing the effectiveness of the prevention and control of female breast cancer in China.

Neurodevelopmental evaluation strategies for children with congenital heart disease aged birth through 5 years: recommendations from the cardiac neurodevelopmental outcome collaborative.

This paper provides specific guidelines for the neurodevelopmental evaluation of children aged birth through 5 years with complex congenital heart disease. There is wide recognition that children with congenital heart disease are at high risk for neurodevelopmental impairments that are first apparent in infancy and often persist as children mature. Impairments among children with complex congenital heart disease cross developmental domains and affect multiple functional abilities. The guidelines provided are derived from the substantial body of research generated over the past 30 years describing the characteristic developmental profiles and the long-term trajectories of children surviving with complex congenital heart conditions. The content and the timing of the guidelines are consistent with the 2012 American Heart Association and the American Academy of Pediatrics scientific statement documenting the need for ongoing developmental monitoring and assessment from infancy through adolescence. The specific guidelines offered in this article were developed by a multidisciplinary clinical research team affiliated with the Cardiac Neurodevelopmental Outcome Collaborative, a not-for-profit organisation established to determine and implement best neurodevelopmental practices for children with congenital heart disease. The guidelines are designed for use in clinical and research applications and offer an abbreviated core protocol and an extended version that expands the scope of the evaluation. The guidelines emphasise the value of early risk identification, use of evidence-based assessment instruments, consideration of family and cultural preferences, and the importance of providing multidimensional community-based services to remediate risk.

The Acute Respiratory Infection Consortium: A Multi-Site, Multi-Disciplinary Clinical Research Network in the Department of Defense.

IntroductionAcute respiratory infections (ARI) result in substantial annual morbidity among military personnel and decrease operational readiness. Herein, we summarize the research efforts of the Infectious Disease Clinical Research Program (IDCRP) related to ARIs.MethodsThe ARI Research Area of the IDCRP was established in response to the 2009 emergence of pandemic influenza A/H1N1. That year, IDCRP investigators deployed the ARI Consortium Natural History Study (ARIC NHS), a multi-centered, longitudinal observational study to assess etiology, epidemiology, and clinical characteristics of influenza-like illness (ILI) and severe acute respiratory infections (SARI) in the U.S. military. The success of this initial effort spurred implementation of several new initiatives. These include the FluPlasma trial, designed to evaluate the efficacy of hyperimmune anti-influenza plasma for the treatment of severe influenza; the self-administered live-attenuated influenza vaccine (SNIF) trial, which assessed the immunogenicity and acceptance of a self-administered live-attenuated influenza vaccine in military personnel; the Study to Address Threats of ARI in Congregate Military Populations (ATARI), a prospective study of ILI transmission, etiology and epidemiology in recruits; and the Flu Breath Test (FBT) study, a preliminary study of exhaled volatile organic compounds (VOC) in influenza patients. In addition, the InFLUenza Patient-Reported Outcome (FLU-PRO) survey, a daily diary to measure influenza symptoms during clinical trials, was developed. Lastly, the Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (PAIVED) study, a two-year randomized trial designed to compare the effectiveness of the three types of licensed vaccines, launched in Fall 2018.ResultsThe on-going ARIC NHS has enrolled over 2000 ILI and SARI cases since its inception, providing data on burden and clinical manifestations of ARI in military personnel and their families. The FluPlasma 2 trial concluded subject enrollment in 2018. Preliminary results from ATARI study show a high frequency of respiratory viruses circulating during the first two weeks of recruit training. Based on assessment of FLU-PRO responses, which were found to be reliable and reproducible, the survey may be a useful tool in clinical trials and epidemiological studies. The Flu Breath Study will complete enrollment in 2019. Findings from PAIVED are intended to provide evidence needed for assessing influenza vaccination policy in the military.ConclusionsThe ARI burden in the armed services remains significant every year and the threat is dynamic given emergent and evolving threats, such as influenzas. With strong successes to date, future initiatives of the ARI Research Area will focus on interventional studies, ARI transmission dynamics in congregate military settings, and determinants of risk of pandemic influenza and other emergent respiratory viruses.

Training a Nonclinician to Become a Leader in Transdisciplinary Clinical Research: Clinical Observerships

As institutions and funders expand their efforts toward multidisciplinary, interdisciplinary, and even transdisciplinary research, there is a substantial need for scientists who can lead such efforts. The traditional image of a leader of transdisciplinary clinical research is a quantitatively savvy clinician conducting research at some point along the continuum from the “bench to the bedside.” However, this is not the only alternative. Nonclinician scientists can also provide effective leadership in multidisciplinary clinical research teams. To foster the development of such nonclinicianleaders, we suggest the completion of a comprehensive clinical observership as an appropriate and valuable training activity. The clinical setting can foster unique insight, providing invaluable training for leadership in translational research. Observing both providers and patients immerses nonclinician scientists in the health care experience, providing them with direct exposure to clinicians, patients, and patients’ families, and thereby motivating patient-centered research.

Characterization of investigators' approach to translational research: a qualitative study.

Little is known about how investigators approach their research programs along the translational research continuum. Many consider the translational continuum to be linear, with research beginning at the bench and concluding with research at the bedside or in the community. We aimed to understand if translational investigators approach and view their research in this fashion. We conducted semistructured individual interviews with 16 graduates of the University of Pittsburgh's Multidisciplinary Clinical Research Scholars Program (KL2) in 2012. Our research revealed three characteristic models. The first model we called "linear" and represented the traditional approach. The second we called "holistic"; these investigators began with central research questions and sought to explore them in every direction of translation, not necessarily taking linear steps. The third model we called "technical"; in this model, investigators focused on a unique technology or methodology and applied it across multiple research contexts. This study found that there are multiple ways that translational investigators approach their research program. Better understanding of these models can help educators and mentors guide investigators so that they can be more productive in their clinical or translational research career.

Editorial introductions

Current Opinion in Rheumatology was launched in 1989. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of Rheumatology is divided into 15 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Joachim SieperJoachim SieperProfessor Joachim Sieper is Head of Rheumatology at the Campus Benjamin Franklin of the Charitè University Hospital in Berlin, Germany. He has a longstanding interest in the pathogenesis, epidemiology, diagnosis and treatment of spondyloarthritides with a focus on ankylosing spondylitis over the recent years. He was involved in several of the pivotal clinical studies showing the dramatic efficacy of TNF-blocking agents in the treatment of ankylosing spondylitis. He is recipient of the Carol-Nachman-Award for Rheumatology (2000) and of the EULAR-Award (2003). Robert D. InmanRobert D. InmanDr Robert D. Inman completed his undergraduate degree at Yale University, USA, and his medical degree at McMaster University, Canada. He did his training in internal medicine at Vanderbilt University, USA, and his fellowship in rheumatology at Cornell University, based at Hospital for Special Surgery, USA. He worked as a research fellow at the Hammersmith Hospital in London, UK, then was appointed Assistant Professor of Medicine at Cornell University. He moved to the University of Toronto, Canada, where he was appointed Professor in the Departments of Medicine and Immunology. He was Director of Rheumatology at the University of Toronto and at University Health Network, Canada, from 1991 to 2002. He is currently Director of the Arthritis Center of Excellence at the University Health Network, Director of the Spondylitis Program at Toronto Western Hospital, and Deputy Physician in Chief, Research at University Health Network. He has held many national and international leadership positions including the member of the Board of Directors of the American College of Rheumatology, Chair of the Medical and Scientific Board of the Spondylitis Association of America. He is currently a member of the Executive Committees of the Assessment of Spondyloarthritis International Society (ASAS) and the Spondyloarthritis Research and Treatment Network (SPARTAN), and is past-President of the Spondyloarthritis Research Consortium of Canada (SPARCC). Kenneth G. SaagKenneth G. SaagKenneth G. Saag, Jane Knight Lowe Professor of Medicine, Division of Clinical Immunology/Rheumatology at the University of Alabama at Birmingham (UAB), USA, and Professor of Epidemiology, at UAB School of Public Health. He is the founding Director of the Deep South Musculoskeletal (DSM) Center for Education and Research on Therapeutics (CERTs) and Director of the AHRQ-supported UAB T32 in Health Services Research. Dr Saag is also Director of the UAB Center for Outcomes and Effectiveness Research (COERE), Director of the UAB Center of Research Translation (NIAMS P50) in Gout and Hyperuricemia, and Co-Director of the Multidisciplinary Clinical Research Center (NIAMS P60). Dr Saag's current research focuses on epidemiology and outcomes of osteoporosis and gout. He studies methods to translate evidence into practice and to design large practical trials for both arthritis and osteoporosis. Dr Saag is on the American College of Rheumatology (ACR) Board of Directors, has been a leader in development of the 2008 and 2011 ACR Recommendations on the Treatment of Rheumatoid Arthritis, and is a member of the ACR Council on Healthcare Economics (CHEC). He received the ACR Rheumatology Research Foundation Excellence in Investigative Mentoring Award in 2013. Dr Saag also serves as Vice President on the Board of Trustees of the National Osteoporosis Foundation (NOF), the Board of Directors of the Gout and Uric Acid Society, and is a member of the National Committee for Quality Assurance (NCQA) Expert Panel, Osteoporosis Advisory Working Group.

Editorial introductions

Editorial introductions

City of hope cancer center hematology–oncology fellowship and hematopoietic stem cell transplantation fellowship

The City of Hope (COH) ACGME-accredited Hematology-Oncology fellowship began in 1978 with two fellows and has grown up to seven fellows per year. It remained as the last fellowship independent of an Internal Medicine Training Program until its affiliation with Harbor-UCLA Internal Medicine Program as the Research Track of the fellowship in 1995. City of Hope Cancer Center is an NCI-designated comprehensive cancer center, a founding member of National Comprehensive Cancer Network, and one of the top medical centers as named by the US News and World Report. This provides an ideal environment for learning patient care and research within both a county hospital and a tertiary teaching hospital setting. In addition, it provides ample opportunities for both basic science and clinical research in the latter years of the fellowship. The fellowship is a fully-funded 3-year program which provides experience through a multidisciplinary approach to prepare trainees for a successful career in academic medicine or private practice.

Current Questions in the Treatment of Advanced Colorectal Cancer: The CAIRO Studies of the Dutch Colorectal Cancer Group

The outcome of patients with advanced colorectal cancer has significantly improved in the past decade because of the development of new treatment strategies. The Dutch Colorectal Cancer Group (DCCG) is a national multidisciplinary clinical research group in The Netherlands. The 3 CAIRO studies of the DCCG address clinically relevant questions in patients with advanced colorectal cancer: the benefit of combination versus sequential therapy, targeting vascular endothelial growth factor and epidermal growth factor receptor, and the role of maintenance therapy. This article presents the outline of these studies and summarizes the current results.

Increased survival using platinum analog combined with gemcitabine as compared to single-agent gemcitabine in advanced pancreatic cancer: pooled analysis of two randomized trials, the GERCOR/GISCAD intergroup study and a German multicenter study

The aim was to evaluate the efficacy of gemcitabine combined with a platinum agent compared to single-agent gemcitabine in a pooled analysis of two randomized trials. The French Multidisciplinary Clinical Research Group (GERCOR)/Italian Group for the Study of Gastrointestinal Tract Cancer (GISCAD) intergroup study comparing gemcitabine plus oxaliplatin to gemcitabine and a German multicenter trial comparing gemcitabine plus cisplatin versus gemcitabine were included in a pooled analysis based on individual patient data. Among 503 evaluable patients, 252 received gemcitabine plus a platinum analog (GP), while 251 patients were treated with gemcitabine alone. For progression-free survival (PFS), the pooled univariate analysis indicated a hazard ratio (HR) of 0.75 (P = 0.0030) in favour of the GP combination. The benefit from the GP combination was greatest in the subgroup of patients with performance status (PS) = 0 (HR = 0.64; P = 0.013). Also overall survival was significantly superior in patients receiving the GP combination (HR = 0.81; P = 0.031). Again, patients with PS = 0 appeared to have a greater benefit from treatment intensification (HR = 0.72; P = 0.063). The pooled analysis of the GERCOR/GISCAD intergroup study and the German multicenter study indicates that the combination of gemcitabine with a platinum analog such as oxaliplatin or cisplatin significantly improves progression-free survival and overall survival as compared to single-agent gemcitabine in advanced pancreatic cancer. The benefit seems to prevail in patients with a good performance status.

Multidisciplinary Clinical Research Centers: Rfa-Ar-05-001

Multidisciplinary Clinical Research Centers: Rfa-Ar-05-001

A New Vision for the National Institutes of Health.

The National Institutes of Health (NIH) has grown from a one-room bacteriology laboratory in 1887 into a multibillion-dollar medical research enterprise. While the NIH has remained true to its original mission—pursuing scientific knowledge to improve people's health—almost everything else about it has changed. Today, NIH comprises 27 Institutes and Centers that sponsor medical research in areas ranging from cancer to diabetes and from genomics to alternative medicine. With the dramatic increases in scientific knowledge as well as the significant changes in diagnosis, treatment, prevention, translation, and delivery of care, researchers must continue to meet the challenges of tomorrow by adopting new strategies today. The NIH is pioneering a vision that will determine what the agency should be and should do in this new “biomedical century.” We are focusing our research energies in three specific areas: exploiting new pathways of discovery; encouraging the formation of interdisciplinary teams of the future; and reengineering the clinical research enterprise. In the first area, we know that scientific research is cost-effective because it saves lives and money in both the short and the long run. Witness our successes in working with AIDS, coronary heart disease, and cancer. We also know that health care costs are continuing to spiral upward, partly due to the aging population which is placing more and more demands on the system. To keep up with the projected increases in costs, the research enterprise must not only accelerate the pace of discovery, but also apply its research results in a timely manner. I believe this is one of the greatest challenges we face in this biomedical century. In the second area, discoveries in human biology are occurring at unprecedented speed, presenting opportunities in medicine that we could only dream about just a few years ago. But these opportunities require a shift in how medical research is conducted and funded. While investigator-initiated projects are the mainstay of NIH-supported research, increasingly these projects involve larger multidisciplinary teams of scientists. These teams might include specialists in disciplines outside biology, such as computer science, imaging, chemistry, mathematics, and informatics. Such multidisciplinary science teams are the wave of the future. I believe that we need to break down the walls that exist between scientific disciplines, inside and outside NIH. We need to foster the growth of interdisciplinary teams in order to maximize the enormous potential of research to improve our lives. For its part, NIH is working to meet this challenge by filling leadership positions at its Institutes and Centers with outstanding scientists who have experience with this new paradigm. In the third area, we need to reengineer the national clinical research enterprise in order to most effectively translate our discoveries into clinical reality. The list of initiatives to undertake is long, but necessary. It includes supporting multidisciplinary clinical research training career paths, introducing innovations in trial design, stimulating translational research, building clinical resources like tissue banks, developing large clinical research networks, and reducing regulatory hurdles. We must also explore a standard clinical research informatics strategy, which will permit the formation of Nation-wide “communities” of clinical researchers made up of academic researchers, qualified community physicians, and patient groups. Alongside our dedicated efforts to pioneer a new vision for NIH is the continuing need to attract the best and brightest researchers. We in the scientific community realize the need to cultivate and nurture minority talent if scientific research is to remain a viable enterprise. Currently, we are experiencing difficulty in retaining researchers from the minority communities, especially through the doctoral levels. We must identify and attract students with potential early on and not let them “fall through the cracks” of academia. We need to consider novel approaches to encourage minority students to remain in mainstream science. Providing students with knowledgeable and supportive mentors and role models could serve as an enticement. NIH has been a leader in supporting minority students throughout their education, with numerous programs and policies in place to increase the number of minorities in research careers. As we take on the challenge of conducting scientific research in the 21st century by pursuing the NIH vision, it is absolutely critical that we find ways to recruit and retain more women and minorities in scientific careers.

An organizational model for developing multidisciplinary clinical research in the academic medical center.

To assess the impact of a new organizational model designed to stimulate multidisciplinary clinical research. We conducted a prospective, 3 1/2-year followup of a research training program for residents, fellows, faculty, nurses, and allied health professionals in rheumatology and orthopedic surgery. Program components included a multidisciplinary clinical research conference, a clinical research methods curriculum, consultations, a patient registry, and regular meetings of a Research Methodology Core group. Measures included participation in each program component and the number of new investigators who developed funded clinical research projects. The multidisciplinary clinical research conference was attended by 369 new health professionals; 218 professionals participated in at least one of the courses; and 280 consultations were provided to 108 professionals. Thirteen new investigators developed 17 new grant proposals, of which 14 were externally funded. Investigators who successfully procured funding for new projects demonstrated significantly more participation in program components compared with those who did not (P < 0.001 overall). Participation in the program was significantly correlated with the development of new prospective patient-based studies. We conclude that our model has the potential to foster such research in other settings.

CLINICAL, PATHOLOGIC, AND SEROLOGIC STUDIES IN SJOEGREN'S SYNDROME; COMBINED CLINICAL STAFF CONFERENCE AT THE NATIONAL INSTITUTES OF HEALTH.

Clinical Staff Conference1 September 1964Clinical, Pathologic, and Serologic Studies in Sjögren's SyndromeCombined Clinical Staff Conference at the National Institutes of HealthJOSEPH J. BUNIM, M.D., F.A.C.P., W. WATSON BUCHANAN, M.D., PAUL T. WERTLAKE, M.D., LEON SOKOLOFF, M.D., KURT J. BLOCH, M.D., J. SWANSON BECK, M.D., F. PAUL ALEPA, M.D.JOSEPH J. BUNIM, M.D., F.A.C.P.Search for more papers by this author, W. WATSON BUCHANAN, M.D.Search for more papers by this author, PAUL T. WERTLAKE, M.D.Search for more papers by this author, LEON SOKOLOFF, M.D.Search for more papers by this author, KURT J. BLOCH, M.D.Search for more papers by this author, J. SWANSON BECK, M.D.Search for more papers by this author, F. PAUL ALEPA, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-61-3-509 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptDr. Joseph J. Bunim: This study on Sjögren's syndrome exemplifies the type of multidisciplinary clinical research for which the facilities and organization of the Clinical Center are especially welldesigned. We embarked on this study almost 5 years ago, and in the course of this time admitted to the Clinical Center 62 patients with this relatively rare disease. Other Institutes contributed patients and participated in some of the studies: the National Institute of Dental Research, the National Institute of Neurological Diseases and Blindness, the National Heart Institute, and the National Institute of Allergy and Infectious Diseases contributed cases or participated in...