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Obstacles Facing Translational Research in Academic Medical Centers
The FASEB Journal
Abstract
Over the last quarter of the 20th century, there has been a boom in biomedical research discoveries that, for the most part, has not been successfully exploited for improving medical therapy or diagnosis. This lack of success is surprising because there is a broad consensus within academic medical centers (AMCs) that a primary mission is to move scientific discoveries into meaningful clinical outcomes, and there are numerous opportunities for doing so. We illustrate the latter point with 10 clinical opportunities for translating scientific discoveries from our field of vascular biology and transplantation. We attribute the limited success of translation to various factors, chief of which is that translation is rarely straightforward and requires continuing research in both the clinic and the laboratory. Translational research is hindered by insufficient targeted resources, a shortage of qualified investigators, an academic culture that hinders collaboration between clinical and laboratory-based investigators, a traditional structure of the AMC that favors departmental efforts over interdisciplinary programs, an increasing regulatory burden, and a lack of specific mechanisms within the AMC for facilitating solutions to these problems. We offer several suggestions to reduce these impediments.
... Journal of Data and Information Science Quantitative 10 Preparing a better procedure for researchers induction Sung et al., 2003) Yes / No Ŧ Qualitative 11 Improvement in ethical approval processes for better decisions and timeliness (Pober, Neuhauser, & Pober, 2001;Sung et al., 2003) Yes / No Ŧ Qualitative 12 Formation of new research teams and projects (Pober et al., 2001) How many projects and teams are established? ...
... Journal of Data and Information Science Quantitative 10 Preparing a better procedure for researchers induction Sung et al., 2003) Yes / No Ŧ Qualitative 11 Improvement in ethical approval processes for better decisions and timeliness (Pober, Neuhauser, & Pober, 2001;Sung et al., 2003) Yes / No Ŧ Qualitative 12 Formation of new research teams and projects (Pober et al., 2001) How many projects and teams are established? ...
... Quantitative 15 Advancement in numbers and quality of research and research teams (Nathan, 2002;Pober et al., 2001;W. M. Trochim et al., 2008;Weiss, 2007) Yes / No ŦŦ Mixed 16 Enhancement of research process, behaviour and procedural protocols Pober et al., 2001;Sung et al., 2003) Yes / No Ŧ Qualitative 17 Recognition and leadership of researchers in the research domain (Kuruvilla et al., 2006;Pober et al., 2001) Yes / No Ŧ Qualitative 18 Improvement of research communication between researchers and research organizations Mankoff et al., 2004) Yes / No Ŧ Qualitative 19 Serving of research staff on a higher level in more advanced organizations at national and international level (Kuruvilla et al., 2006;Sung et al., 2003) Yes / No Ŧ Qualitative 20 Improvement in research culture and overall environment Kessler & Glasgow, 2011;Mankoff et al., 2004;Pober et al., 2001;Sung et al., 2003) Yes / No Ŧ Qualitative 21 Identification and overcoming of the research process constraints Pober et al., 2001) Yes / No Ŧ Qualitative 22 Improved willingness and tangible measures for practice-based and applied research (Westfall, Mold, & Fagnan, 2007) Yes / No Ŧ Qualitative 23 Development of improved analytical methods for existing data (Kessler & Glasgow, 2011;Kuruvilla et al., 2006;W. ...
Purpose
This study aims to classify research impact indicators based on their characteristics and scope. A concept of evidence-based nomenclature of research impact (RI) indicator has been introduced for generalization and transformation of scope.
Design/methodology/approch
Literature was collected related to the research impact assessment. It was categorized in conceptual and applied case studies. One hundred and nineteen indicators were selected to prepare classification and nomenclature. The nomenclature was developed based on the principle—“every indicator is a contextual-function to explain the impact”. Every indicator was disintegrated into three parts, i.e. Function, Domain, and Target Areas.
Findings
The main functions of research impact indicators express improvement (63%), recognition (23%), and creation/development (14%). The focus of research impact indicators in literature is more towards the academic domain (59%) whereas the environment/sustainability domain is least considered (4%). As a result, research impact related to the research aspects is felt the most (29%). Other target areas include system and services, methods and procedures, networking, planning, policy development, economic aspects and commercialisation, etc.
Research limitations
This research applied to 119 research impact indicators. However, the inclusion of additional indicators may change the result.
Practical implications
The plausible effect of nomenclature is a better organization of indicators with appropriate tags of functions, domains, and target areas. This approach also provides a framework of indicator generalization and transformation. Therefore, similar indicators can be applied in other fields and target areas with modifications.
Originality/value
The development of nomenclature for research impact indicators is a novel approach in scientometrics. It is developed on the same line as presented in other scientific disciplines, where fundamental objects need to classify on common standards such as biology and chemistry.
... Journal of Data and Information Science Quantitative 10 Preparing a better procedure for researchers induction Sung et al., 2003) Yes / No Ŧ Qualitative 11 Improvement in ethical approval processes for better decisions and timeliness (Pober, Neuhauser, & Pober, 2001;Sung et al., 2003) Yes / No Ŧ Qualitative 12 Formation of new research teams and projects (Pober et al., 2001) How many projects and teams are established? ...
... Journal of Data and Information Science Quantitative 10 Preparing a better procedure for researchers induction Sung et al., 2003) Yes / No Ŧ Qualitative 11 Improvement in ethical approval processes for better decisions and timeliness (Pober, Neuhauser, & Pober, 2001;Sung et al., 2003) Yes / No Ŧ Qualitative 12 Formation of new research teams and projects (Pober et al., 2001) How many projects and teams are established? ...
... Quantitative 15 Advancement in numbers and quality of research and research teams (Nathan, 2002;Pober et al., 2001;W. M. Trochim et al., 2008;Weiss, 2007) Yes / No ŦŦ Mixed 16 Enhancement of research process, behaviour and procedural protocols Pober et al., 2001;Sung et al., 2003) Yes / No Ŧ Qualitative 17 Recognition and leadership of researchers in the research domain (Kuruvilla et al., 2006;Pober et al., 2001) Yes / No Ŧ Qualitative 18 Improvement of research communication between researchers and research organizations Mankoff et al., 2004) Yes / No Ŧ Qualitative 19 Serving of research staff on a higher level in more advanced organizations at national and international level (Kuruvilla et al., 2006;Sung et al., 2003) Yes / No Ŧ Qualitative 20 Improvement in research culture and overall environment Kessler & Glasgow, 2011;Mankoff et al., 2004;Pober et al., 2001;Sung et al., 2003) Yes / No Ŧ Qualitative 21 Identification and overcoming of the research process constraints Pober et al., 2001) Yes / No Ŧ Qualitative 22 Improved willingness and tangible measures for practice-based and applied research (Westfall, Mold, & Fagnan, 2007) Yes / No Ŧ Qualitative 23 Development of improved analytical methods for existing data (Kessler & Glasgow, 2011;Kuruvilla et al., 2006;W. ...
Purpose: This study aims to classify research impact indicators based on their characteristics and scope. A concept of evidence-based nomenclature of research impact (RI) indicator has been introduced for generalization and transformation of scope. Design/methodology/approch: Literature was collected related to the research impact assessment. It was categorized in conceptual and applied case studies. One hundred and nineteen indicators were selected to prepare classification and nomenclature. The nomenclature was developed based on the principle-"every indicator is a contextual-function to explain the impact". Every indicator was disintegrated into three parts, i.e. Function, Domain, and Target Areas. Findings: The main functions of research impact indicators express improvement (63%), recognition (23%), and creation/development (14%). The focus of research impact indicators in literature is more towards the academic domain (59%) whereas the environment/ sustainability domain is least considered (4%). As a result, research impact related to the research aspects is felt the most (29%). Other target areas include system and services, methods and procedures, networking, planning, policy development, economic aspects and commercialisation, etc. Research limitations: This research applied to 119 research impact indicators. However, the inclusion of additional indicators may change the result. Practical implications: The plausible effect of nomenclature is a better organization of indicators with appropriate tags of functions, domains, and target areas. This approach also provides a framework of indicator generalization and transformation. Therefore, similar indicators can be applied in other fields and target areas with modifications. Originality/value: The development of nomenclature for research impact indicators is a novel approach in scientometrics. It is developed on the same line as presented in other scientific disciplines, where fundamental objects need to classify on common standards such as biology and chemistry.
... The work experiences of multiple competing roles are influenced by many factors that in turn impact role performance of physician scientists in AMCs. Further impact exists in translation of science from the laboratory to the clinic and from the AMC (Crowley et al., 2004;Pober, Neuhauser & Pober, 2001;Sung et al., 2003) to the practice of medicine (Westfall et al., 2007;Westfall et al., 2009;Zerhouni, 2007). It is important to understand work complexities of physician scientists, along with discovering emergent factors not yet studied, to better understand lived experiences in AMCs. ...
... Institutional mission is critical because the majority of clinical research occurs in the AMC setting, but most patients receive care in outpatient primary care settings (Westfall et al., 2007). Many agree that the primary mission of AMCs is to move scientific discovery to meaningful clinical outcomes (Pober et al., 2001;Zerhouni, 2005;Zerhouni, 2007). Yet, these institutions continue to face serious obstacles around funding (Crowley et al., 2004), regulatory barriers (Kim, Ubel, & De Vries, 2009), internal undervaluation of AMC mission, and the professional satisfaction for physician scientists to pursue a career solely in clinical medicine (Dickler, Korn, & Gabbe, 2006). ...
This study investigated factors influencing success of physician scientists in Academic Medical Centers. These organizations and individuals drive healthcare in the United States. Translation of scientific discovery to medical practice moves at an astoundingly slow and ineffective rate. We must understand what contributes to physician scientist success to speed up translation. Through a lens of dialectic process theory, a grounded theory approach identified emergent factors from lived experiences of 31 individuals, at various experience levels, with MD and PhD degrees. Role balance, autonomy, organizational support, teamwork, life-cycle mentorship, and relational capacity were relevant factors impacting success. Role balance was important for success. Teamwork, organizational support, and life-cycle mentorship helped individuals grow, achieve balance, and respect, but relational capacity emerged as a critical driver for realizing both individual and organizational success. One person cannot execute these complex roles on their own, but development of deep and meaningful relationships through teamwork, collaboration, and life-cycle mentorship are essential for life satisfaction and success.
... However, working across sectors is inherently challenging and demands specific financial and human resources. Many academic and research institutions already struggle to communicate across their own groups and departments and to offer opportunities beyond a mono-disciplinary career path [4][5][6][7]. This might be attributed to a culture and structural organisation that are barely conducive to operating in an interdisciplinary manner. ...
... This might be attributed to a culture and structural organisation that are barely conducive to operating in an interdisciplinary manner. Coupled with a shortage of "translational investigators", as described for example, in the medicine area (e.g., staff members trained to perform translational research and bridging the gap between innovation and implementation) [4,5], successful translations of scientific discoveries into practice are scarce. In addition, financial support is often inadequate, which requires applying to a variety of sources to cover the whole innovation to implementation cycle, widening intra-departmental gaps, and impeding translational research efforts. ...
Research that takes a pro-active role in bridging science and practice holds promise to accelerate progress towards the Sustainable Development Goals. While passing on best practices outside of academia, inspiration can be drawn from pressing global challenges. Using Swiss research institutions that maintain partnerships with low- and middle-income countries as a case study, the purpose of this study was to identify synergies between research and services for development (R&S4D). We mapped Swiss research institutions that host both types of activities and identified the strengths, weaknesses, opportunities, and threats (SWOT) linked to their hybrid models. Semi-structured interviews were conducted with representatives from the identified institutions, and data were analysed using the Framework Method. Strengths of combining R&S4D were observed on four levels: (i) individual (i.e., high employability outside academia); (ii) project (i.e., higher quality and practical relevance); (iii) entity (i.e., flexibility regarding funders, resources, and partners); and (iv) sustainable development (i.e., more impactful work). The main weaknesses were named as a decrease in the scientific quality of research projects specifically and inefficiency/lack of feasibility of implementation services. A lack of career paths and positions for individuals who wish to pursue academic research alongside services was identified as a threat. The Universities of Applied Sciences account for the largest share of hybrid positions in Switzerland; increasing their currently limited funding for research and international activities represents an opportunity. Our reserch adds a unique viewpoint to the discussion on the role of academia in supporting society to move towards sustainable development. It does so by exploring whether and how the concept of multisectoriality can work as an integral part of academia at the individual and the institutional level.
... a producción de nuevo conocimiento científico es fundamental en el desarrollo de las sociedades. En salud, para que logre ser un beneficio es esencial que los médicos puedan plantear y desarrollar dudas clínicamente relevantes 1,2 . En este sentido, el aprendizaje científico es fundamental para la formación médica y el continuo progreso del conocimiento biomédico, al producir nuevos investigadores 2,3 . ...
... En salud, para que logre ser un beneficio es esencial que los médicos puedan plantear y desarrollar dudas clínicamente relevantes 1,2 . En este sentido, el aprendizaje científico es fundamental para la formación médica y el continuo progreso del conocimiento biomédico, al producir nuevos investigadores 2,3 . ...
Background:
The participation of medical students in research generates professional, scientific, and personal benefits for the student.
Aim:
To evaluate the interest and opportunities for medical students in Chile to participate in scientific research and their perceptions about factors influencing research.
Material and Methods:
All students attending the 2018 Chilean Congress for Medical Students were invited to answer a 44 questions survey about interest and opportunities to participate in research.
Results:
The survey was answered by 489 of the 538 students attending the congress. Eighty five percent referred interest in conducting scientific research, but only 47% had the opportunity to actively participate in a research project. The main research area providing opportunities was epidemiology and the main form to access a research project was through direct contact with a medical professor or researcher. Seventy seven percent of respondents had courses of scientific investigation in their medical curriculum and 92% had a scientific society for medical students in their university.
Conclusions:
Respondents showed a great deal of interest in participating in scientific research. However, there is a gap between this interest and the available opportunities. Medical professors should promote and facilitate the participation of their students in research.
... However, these advances in basic biomedical research showed only a few examples of a successful application of the findings of such research in medical practice. Such applications are commonly described as 'translation' , as the "process of translating discoveries in the laboratory into clinical interventions for the diagnosis, treatment, prognosis, or prevention of disease with a direct benefit to human health" (15,16). ...
... The development and maintenance of infrastructures of scientific laboratories is considered a major goal for academic centers promoting translational cancer research programs. Among infrastructures favoring translational research, centralized facilities characterized by a shared, multidisciplinary use (by different departments, divisions, research units) of expensive laboratory instrumentation, or by a complex computer hardware and software, and / or by high professional skills are necessary to maintain or improve institutional scientific competitiveness (16,17). ...
Advance in molecular biology and the new technologies for biomedical research are being rapidly introduced into the research of complex pathologies worldwide. Implementation of these technologies, however, needs substantial financial resources for the equipment and for training the specialists. The rapid development of biomedical research over the past decade increases the risk of moral ageing of the implemented technologies and raises doubts as to whether countries with limited financial resources could afford them. In this article, we share our institutional experience in the implementation of post-genomic technologies in cancer research in Lithuania and stress the need of modern infrastructure in biomedical research, despite the needed efforts and associated risks.
Keywords: postgenomic technologies, cancer research
... There are several issues hindering the advancement of translational research studies in developing countries. These include limited funding, insufficient research evaluation and recognition, absence of government model or consortium of research, and insufficient communication among researchers and stakeholders [1,2]. Limited funding is a principal barrier in both performing and implementing translational research [3]. ...
... As translational research is mostly expensive, multiple sources of funding is needed. These include governmental health agencies, private foundations, and self-funding [2]. In most countries, medical scientists rely mainly on the funding source given by the government, either annually or biannually [4]. ...
Translational research carries over fundamental laboratory research findings into clinical and community settings in order to ‘translate’ the findings into practice. In addition to its potential in accelerating the time of basic discoveries to be delivered into the population, translational studies also provide opportunities for interdisciplinary collaborations in identifying knowledge gaps. However, several issues hindering the advancement of translational research studies have risen in developing countries, such as limited funding, insufficient research evaluation and recognition, absence of government model or consortium, and insufficient communication among researchers and stakeholders. While the original concept of the ‘bench to bedside’ has been known for years, the practice of bilateral flow from bench to bedside, and back to the bench was found lacking. Lack of interactions and involvement of the clinicians, community and resources further deplete translational ability of the research itself. Without understanding the priorities and the environment in which the decision makers work, specific research aims needed by the communities may be failed to be formulated and may result in devaluation of research by formulating similar key questions repetitively. The current commentary aimed to highlight the importance of connecting population health systems, basic demands, and academic institutions, to own the issues, to address the issues, and to translate research findings.
... As Pober et al. (2001) suggest, the first step to tackle impediments to TR is to recognize the nature of TR and provide adequate funding for improvement, e.g. by increasing the pool of translational researchers and restructuring of the academic environment. It remains a challenge to identify the most effective selection criteria for a potentially disruptive innovation. ...
... Pober et al. argue that academic medical centres (AMCs) that integrate medical schools and hospitals are the most suitable place for TR as they bring together clinical and basic science researchers. However an interdisciplinary organization would require major changes including the replacement of the traditional departmental structure of AMCs since the traditional physical separation between physicians and science investigators discourages their interpersonnel communication (Pober et al. 2001). Emerging private translational platforms that provide case-specific services such as quality control, potency tests, regulatory assistance and phase 1 and 2 clinical trials appear as alternative solutions to the shortage of an academic infrastructure. ...
Advances at the interface between the biological sciences and engineering are giving rise to emerging research fields such as synthetic biology. Harnessing the potential of synthetic biology requires timely and adequate translation into clinical practice. However, the translational research enterprise is currently facing fundamental obstacles that slow down the transition of scientific discoveries from the laboratory to the patient bedside. These obstacles including scarce financial resources and deficiency of organizational and logistic settings are widely discussed as primary impediments to translational research. In addition, a number of socio-ethical considerations inherent in translational research need to be addressed. As the translational capacity of synthetic biology is tightly linked to its social acceptance and ethical approval, ethical limitations may—together with financial and organizational problems—be co-determinants of suboptimal translation. Therefore, an early assessment of such limitations will contribute to proactively favor successful translation and prevent the promising potential of synthetic biology from remaining under-expressed. Through the discussion of two case-specific inventions in synthetic biology and their associated ethical implications, we illustrate the socio-ethical challenges ahead in the process of implementing synthetic biology into clinical practice. Since reducing the translational lag is essential for delivering the benefits of basic biomedical research to society at large and promoting global health, we advocate a moral obligation to accelerating translational research: the “translational imperative.”
... Furthermore, an increasing policy focus on 'translational research' highlights AHSCs as appropriate vehicles through which to deliver research from 'bench to bedside' (Pober et al., 2001). As noted below, translational research is traditionally characterised as a linear process which takes findings from basic research and delivers them as innovations in clinical practice, overcoming gaps along the way (Cooksey, 2006). ...
... AHSCs are seen as centres for the delivery of research from 'bench to bedside' due to their joint missions of high quality research and healthcare delivery. Two papers usefully describe obstacles (and potential solutions) to the delivery of translational research in the AHSC setting (Cripe et al., 2005;Pober et al., 2001) and Weston et al. (2010) attempt to assess the involvement of AHSC faculty in translational research. ...
The problem of mobilising research generated knowledge into practice has received increasing attention from policy makers and scholars internationally. Academic Health Science Centres (AHSCs) are partnerships between universities and hospitals which aim to use research discoveries to improve patient care. Despite their complexity and recent international spread, they have not received much attention from social science. This thesis, as a study of this emergent organisational form, contributes to addressing this gap. It conceptualises the ‘bench to bedside’ knowledge mobilisation process within two English AHSC cases as ‘boundary work’ between the domains of research and clinical practice. By analysing qualitative data collected through semi structured interviews (48), observations (130+ hours) and documentary analysis at micro (research/clinical teams) and meso (organisational) levels, it addressed the research question: What boundary processes mobilise knowledge within Academic Health Science Centres? Epistemic, professional and organisational framings were all important conceptualisations of the research/clinical practice boundary. Epistemic elements motivated knowledge mobilisation, with organisational boundaries often proving least permeable. The most effective boundary work encompassed all three. Networked forms of governance prevailed at the organisational level. Joint fields of practice emerged at the micro level with key (instrumental and symbolic) spanning mechanisms including professional hybrids as boundary spanners (e.g. clinician scientists), and objects (e.g. shared data). The ‘bench to bedside’ heuristic operated as an overarching boundary concept, motivationally powerful yet vague enough to bring together diverse groups. This study is one of few to consider the early development of AHSCs from a social science perspective. It contributes empirically and theoretically to the knowledge mobilisation and boundary literature by focussing analysis on the research and clinical practice boundary (as a space for new practice) and the people and objects that work across it, particularly centring on the under-researched role of organisation in this process.
... Even though translational research requires the incorporation of basic science and clinical research, the human capital required to undertake translational activity may be limited by institutional or training traditions that compartmentalize the biomedical career into basic or clinical research. Ideally, medical researchers who have scientific training in basic science, such as a PhD/MD, can facilitate the translational process by combining clinical expertise with advanced scientific knowledge (Pober et al. 2001). However, individual researchers do not have strong incentives to obtain a PhD/MD because the completion of the joint degree usually requires eight years (Brass et al., 2015). ...
... However, individual researchers do not have strong incentives to obtain a PhD/MD because the completion of the joint degree usually requires eight years (Brass et al., 2015). Even after obtaining a PhD/MD, medical researchers may have less available time to conduct clinical and translational research because of pressure for patient treatment and necessary lab-based research (Goldstein &Brown, 1997, Jones andGold, 1998;2001; see also Lovejoy and Clark, 1995) In addition, the institutional structure of the academic medical research centers (AMCs) may discourage biomedical scientists from translational activity as AMCs usually physically separate basic scientists and clinical researchers (Pober et al. 2001). Scientists who have a doctorate in a basic science field may be employed in academic settings that require high academic productivity (Ley & Rosenberg, 2005) resulting in greater commitment to basic science than to clinical research or application (Morgan., et al., 2011;Goldstein & Brown, 1997;Ley & Rosenberg, 2005). ...
This paper examines how human and social capital affect the production of medical innovation outputs along the translational research continuum. Despite efforts like the NIH CTSA program to institutionalize translational research, significant gaps exist between the different stages of the translational process due in large part to the compartmentalization of medical careers and disciplinary specialization. Applying human and social capital theories, the paper develops tests hypotheses using a multi-level model and data from a network survey of researchers at the University of Illinois at Chicago to explain production of translational innovation (dissemination, new clinical activity, and new intervention). Findings show that human capital variables are less important than social capital variables. Effects of cross-disciplinarity and translational network size are weak and only associated to one of the innovation types. By contrast exchange of a variety of resources across the collaborative relationship is consistently important for the production innovations.
... Furthermore, leadership across AMCs expressed concerns that the clinical research workforce and infrastructure needed to be strengthened to keep up with advances in basic science research [3]. While AMCs have been committed to meeting these objectives, major barriers, including a lack of trained researchers, integrated systems, standardized policies and procedures, competent staffing, and appropriate resources persist [4,5]. In particular, fragmented infrastructure, coupled with inexperienced staff and high turnover, was adversely affecting the quality and value of clinical research [6,7]. ...
Quality clinical research is essential for health care progress and is the mission of academic health centers. Yet ensuring quality depends on an institution’s ability to measure, control, and respond to metrics of trial performance. Uninformed clinical research provides little benefit to health care, drains institutional resources, and may waste participants' time and commitment. Opportunities for ensuring high-quality research are multifactorial, including training, evaluation, and retention of research workforces; operational efficiencies; and standardizing policies and procedures. Duke University School of Medicine has committed to improving the quality and informativeness of our clinical research enterprise through investments in infrastructure with significant focus on optimizing research management system integration as a foundational element for quality management. To address prior technology limitations, Duke has optimized Advarra’s OnCore for this purpose by seamlessly integrating with the IRB system, electronic health record, and general ledger. Our goal was to create a standardized clinical research experience to manage research from inception to closeout. Key drivers of implementation include transparency of research process data and generating metrics aligned with institutional goals. Since implementation, Duke has leveraged OnCore data to measure, track, and report metrics resulting in improvements in clinical research conduct and quality.
... Translational research The term translational is used in medicine to describe research that aims to transform advances in basic knowledge (biological or clinical) to applications to human health (Butte, 2008;Rubio et al., 2010). Translational research is a distinct discipline bridging basic science and applications (Pober et al., 2001;Reis et al., 2010). We adopt the term Translational NLP to describe research bridging the gap between basic and applied NLP research, and aiming to understand the processes by which each informs the other. ...
Natural language processing (NLP) research combines the study of universal principles, through basic science, with applied science targeting specific use cases and settings. However, the process of exchange between basic NLP and applications is often assumed to emerge naturally, resulting in many innovations going unapplied and many important questions left unstudied. We describe a new paradigm of Translational NLP, which aims to structure and facilitate the processes by which basic and applied NLP research inform one another. Translational NLP thus presents a third research paradigm, focused on understanding the challenges posed by application needs and how these challenges can drive innovation in basic science and technology design. We show that many significant advances in NLP research have emerged from the intersection of basic principles with application needs, and present a conceptual framework outlining the stakeholders and key questions in translational research. Our framework provides a roadmap for developing Translational NLP as a dedicated research area, and identifies general translational principles to facilitate exchange between basic and applied research.
... Nursing selected randomly. Inclusion criteria is all those who are willing to participate and exclusion criteria is those who are un willing to participate [7][8]. Informed written consent is taken from the study subjects after assuring the anonymity. ...
A study to assess the knowledge, opinion of faculty and post graduate students of nursing regarding translational Research in nursing in Tirupathi was conducted on 50 nursing faculty and 50 nursing post graduate students in Tirupathi, with the objectives to find out 1. Knowledge regarding translational Research 2. Opinion regarding translational research. Method and Material It was an incidental study conducted by the investigator when nearly 500 nursing personnel came to participate in the national workshop organised by Sri Padmavathi Mahila Visva vidyalayam in Tirupathi. The study comprised of survey questionnaire of multiple choice type to elicit the information and an opinion check list. The sample of study is selected randomly from 2 groups comprised of faculty and post graduate students. The data was collected before starting of the Workshop when participants assembled for registration. Results showed that the knowledge score's levels of nursing faculty was almost the same as that of post graduate nursing students. However, both groups showed slightly different responses on opinionnaire regarding translational research. Conclusion Translational research in nursing is not a myth and distance dream but can be a realty.
... Mye god forskning har antakelig stoppet opp før den når stadiet der all potensiell kunnskap et «utvunnet», fordi forskergruppene har manglet kompetansen eller ressursene til å gå videre til neste steg (9)(10)(11). Det kan vaere vanskelig å overbevise myndighetene eller andre om å fortsette å støtte et prosjekt som ikke kan vise til muligheter for anvendelige resultater i overskuelig fremtid. ...
... Other studies support the existence of the barriers revealed in this study. For example, in 2001, in highlighting the failures of collaborations to translate scientific discoveries into practice, authors attribute these failures to insufficient targeted resources, a shortage of qualified investigators, increasing regulatory burden, and a lack of mechanisms for addressing the problems that arise [56]. On the other hand, the facilitators reported by investigators related to their partnerships, multidisciplinary teams, management, infrastructures and resources. ...
Background
Collaboration between biomedical research and community-based primary health care actors is essential to translate evidence into clinical practice. However, little is known about the characteristics and impacts of implementing collaborative models. Thus, we sought to identify and describe collaboration models that bridge biomedical research and community-based primary health care in chronic disease management.
Methods
We conducted a scoping review using Medline, Embase, Web of Science, and Cochrane Library from inception to November 2020, to identify studies describing or evaluating collaboration models. We also searched grey literature, screened reference lists, and contacted experts to retrieve further relevant references. The list of studies was then refined using more specific inclusion and exclusion criteria. Two reviewers independently selected studies and extracted relevant data (characteristics of studies, participants, collaborations, and outcomes). No bias assessment was performed. A panel of experts in the field was consulted to interpret the data. Results were presented with descriptive statistics and narrative synthesis.
Results
Thirteen studies presenting 20 unique collaboration models were included. These studies were conducted in North America ( n = 7), Europe ( n = 5) and Asia ( n = 1). Collaborations were implemented between 1967 and 2014. They involved a variety of profiles including biomedical researchers ( n = 20); community-based primary health care actors ( n = 20); clinical researchers ( n = 15); medical specialists ( n = 6); and patients, citizens, or users ( n = 5). The main clinical focus was cardiovascular disease ( n = 8). Almost half of the collaborations operated at an international level ( n = 9) and the majority adopted either a network ( n = 7) or hierarchical structure ( n = 6). We identified significant implementation barriers (lack of knowledge, financial support, and robust management structure) and collaboration facilitators (partnership, cooperation, multidisciplinary research teams). Out of the 20 included collaboration models, seven reported measurable impact.
Conclusion
We identified a large variety of collaboration models representing several clinical and research profiles and fields of expertise. As they are all based in high-income countries, further research should aim to identify collaborations in low-income countries, to determine which models and/or characteristics, could better translate evidence into clinical practice in these contexts.
... . The general conclusion is that translation in health refers to converting information from basic science to improvements in clinical and, ultimately, public health outcomes (Drolet & Lorenzi, 2011;Marincola, 2003;Pober et al., 2001;Rubio et al., 2010;Sussman et al., 2006); one that entails a long and complicated process. In a widely cited review, Balas and Boren claim that it takes 17 years to translate only 14% of original health/medical research into practice, and that a majority of original research is never translated into practice (Balas & Boren, 2000). ...
Comparative effectiveness research (CER), which refers to an evaluation of the clinical effectiveness of two or more medical interventions that are used to treat the same condition, has the potential to inform decision-making in both policy circles and physicians’ exam rooms. The ability of stakeholders to translate that research into practice has important implications for health outcomes, but the impact of information sources on physicians in translating CER remains understudied. This project examines the source-related influences on and motivations of cardiologists with respect to willingness to make changes in their practice based on emerging CER results. The results from this survey of cardiologists (N = 42) indicate that the source of information (including perceived credibility of those sources) matters greatly to cardiologists when deciding whether to make a change in practice. These findings suggest data-based implications for researchers and practitioners that are engaged in closing the CER translation gap.
... Translational research-The term translational is used in medicine to describe research that aims to transform advances in basic knowledge (biological or clinical) to applications to human health (Butte, 2008;Rubio et al., 2010). Translational research is a distinct discipline bridging basic science and applications (Pober et al., 2001;Reis et al., 2010). We adopt the term Translational NLP to describe research bridging the gap between basic and applied NLP research, and aiming to understand the processes by which each informs the other. ...
Natural language processing (NLP) research combines the study of universal principles, through basic science, with applied science targeting specific use cases and settings. However, the process of exchange between basic NLP and applications is often assumed to emerge naturally, resulting in many innovations going unapplied and many important questions left unstudied. We describe a new paradigm of Translational NLP, which aims to structure and facilitate the processes by which basic and applied NLP research inform one another. Translational NLP thus presents a third research paradigm, focused on understanding the challenges posed by application needs and how these challenges can drive innovation in basic science and technology design. We show that many significant advances in NLP research have emerged from the intersection of basic principles with application needs, and present a conceptual framework outlining the stakeholders and key questions in translational research. Our framework provides a roadmap for developing Translational NLP as a dedicated research area, and identifies general translational principles to facilitate exchange between basic and applied research.
... Translational research The term translational is used in medicine to describe research that aims to transform advances in basic knowledge (biological or clinical) to applications to human health (Butte, 2008;Rubio et al., 2010). Translational research is a distinct discipline bridging basic science and applications (Pober et al., 2001;Reis et al., 2010). We adopt the term Translational NLP to describe research bridging the gap between basic and applied NLP research, and aiming to understand the processes by which each informs the other. ...
Natural language processing (NLP) research combines the study of universal principles, through basic science, with applied science targeting specific use cases and settings. However, the process of exchange between basic NLP and applications is often assumed to emerge naturally, resulting in many innovations going unapplied and many important questions left unstudied. We describe a new paradigm of Translational NLP, which aims to structure and facilitate the processes by which basic and applied NLP research inform one another. Translational NLP thus presents a third research paradigm, focused on understanding the challenges posed by application needs and how these challenges can drive innovation in basic science and technology design. We show that many significant advances in NLP research have emerged from the intersection of basic principles with application needs, and present a conceptual framework outlining the stakeholders and key questions in translational research. Our framework provides a roadmap for developing Translational NLP as a dedicated research area, and identifies general translational principles to facilitate exchange between basic and applied research.
... Without in-depth accounting, it is impossible to confirm this contention. Moreover, there is evidence that translational research within AMCs is not straightforward and suffers from several challenges peculiar to such often large and bureaucratic hospitals [6]. Moreover, the lead author of the current article, a lifelong academic physician and medical device entrepreneur, has observed little correlation between the higher costs of academic medical centers and true translational research, i.e. research that spans the "bench to bedside" divide, with a deliberate focus on actually making it to the patient bedside. ...
Skin cancers are the most common malignancy and are especially common among light-skinned individuals in sun-exposed areas. While in many cases, a characteristic or classic appearance of the lesion is sufficient to make a definitive diagnosis, shave biopsy remains an important procedure when diagnosing many such raised lesions. Over the span of two months, a 66-year-old Caucasian male noted the appearance of a small, raised pruritic scaly lesion over his right upper chest. The differential diagnosis included both cancerous and benign lesions. During a 15-minute clinic visit, a simple shave biopsy was performed, and additionally, 10 small actinic keratoses on the patient's arms, legs, and back were treated with cryotherapy using liquid nitrogen. Later, a histologic examination of the biopsied lesion revealed a benign lichenoid keratosis. The patient was billed $10,187 for this outpatient experience.
... Earlier models of translation, which viewed the process of producing tangible outcomes from scientific research in terms of a path -bench to bedside -strewn with obstacles to be overcome (e.g. Pober, Neuhauser and Pober 2001), have now largely been superseded. Many scientists and funders acknowledge the complex trajectories involved in translation and the challenges of fostering collaborative relations required to sustain interactive research (Collins 2011; Collins and Tabak 2014; Moher et al. 2016;Zerhouni 2003). ...
We investigate translation in biomedicine by exploring how researchers supported by the British Pharmacological Society's Integrative Pharmacology Fund (IPF) have responded to increasing translational aspirations within pre-clinical animal research. The IPF sought to enhance institutional capacities, collaborative practices, and personal skills within in vivo research in the quintessentially translational fields of pharmacology, physiology and toxicology. We identify three manifestations of the influence of translational aspirations: 1) shifting from the standardisation of animal models to the alignment of research on animals with human therapeutic pathways ; 2) expanding relationalities of care in animal research from a focus on the animal body to institutional arrangements around clinical care; and 3) changing training around research ethics, integrity and good statistical practice. Concluding, we discuss the value of working interactively with those involved in the changing practices of animal research and translation as a means to foster reflexivity about what matters when 'training to translate'.
... Translation as a concept emerged in medicine in the 1990s [2]. Observing a growing number of biomedical research discoveries that had not been exploited to improve clinical outcomes [3], biomedical researchers argued for new research approaches in which the application of research results is an explicit part of the research plan-that indeed, have the goal of translating research results into ''new approaches for prevention, diagnosis, and treatment of disease'' [4]. Translational medicine has since become a major part of the biomedical research enterprise. ...
A growing gap between progress in biological knowledge and improved health outcomes inspired the new discipline of translational medicine, in which the application of new knowledge is an explicit part of a research plan. Abramson and Parashar argue that a similar gap between complex computational technologies and ever-more-challenging applications demands an analogous discipline of translational computer science, in which the deliberate movement of research results into large-scale practice becomes a central research focus rather than an afterthought. We revisit from this perspective the development and application of grid computing from the mid-1990s onwards, and find that a translational framing is useful for understanding the technology’s development and impact. We discuss how the development of grid computing infrastructure, and the Globus Toolkit, in particular, benefited from a translational approach. We identify lessons learned that can be applied to other translational computer science initiatives.
... Translation as a concept emerged in medicine in the 1990s [31]. Observing a growing number of biomedical research discoveries that had not been exploited to improve clinical outcomes [37], biomedical researchers argued for new research approaches in which the application of research results is an explicit part of the research plan-that indeed, have the goal of translating research results into "new approaches for prevention, diagnosis, and treatment of disease" [46]. Translational medicine has since become a major part of the biomedical research enterprise. ...
A growing gap between progress in biological knowledge and improved health outcomes inspired the new discipline of translational medicine, in which the application of new knowledge is an explicit part of a research plan. Abramson and Parashar argue that a similar gap between complex computational technologies and ever-more-challenging applications demands an analogous discipline of translational computer science, in which the deliberate movement of research results into large-scale practice becomes a central research focus rather than an afterthought. We revisit from this perspective the development and application of grid computing from the mid-1990s onwards, and find that a translational framing is useful for understanding the technology's development and impact. We discuss how the development of grid computing infrastructure, and the Globus Toolkit, in particular, benefited from a translational approach. We identify lessons learned that can be applied to other translational computer science initiatives.
... Data suggest that it can show a return on investment (16)(17)(18), however such an infrastructure requires a substantial and long-lasting investment of money and time in trainees, mentors and core research facilities. Development and maintenance of adequate shared infrastructures is also considered a major goal for academic centers promoting translational research programs (19,20). Centralized "hubs" or "cores" that are characterized by shared, multidisciplinary use of expensive laboratory equipment, data power and complex professional skills (e.g., genomics, imaging, flow cytometry, animal facilities, data, and biobanking) are a necessity to maintain institutional competitiveness among universities and research centers around the world. ...
Biomedical scientists aim to contribute to further understanding of disease pathogenesis and to develop new diagnostic and therapeutic tools that relieve disease burden. Yet the majority of biomedical scientists do not develop their academic career or professional identity as “translational scientists,” and are not actively involved in the continuum from scientific concept to development of new strategies that change medical practice. The collaborative nature of translational medicine and the lengthy process of bringing innovative findings from bench to bedside conflict with established pathways of building a career in academia. This collaborative approach also poses a problem for evaluating individual contributions and progress. The traditional evaluation of scientific success measured by the impact and number of publications and grants scientists achieve is inadequate when the product is a team effort that may take decades to complete. Further, where scientists are trained to be independent thinkers and to establish unique scientific niches, translational medicine depends on combining individual insights and strengths for the greater good. Training programs that are specifically geared to prepare scientists for a career in translational medicine are not widespread. In addition, the legal, regulatory, scientific and clinical infrastructure and support required for translational research is often underdeveloped in academic institutions and funding organizations, further discouraging the development and success of translational scientists in the academic setting. In this perspective we discuss challenges and potential solutions that could allow for physicians, physician scientists and basic scientists to develop a professional identity and a fruitful career in translational medicine.
... Clinical research informatics (CRI) is an evolving field widely recognized as crucial for transforming and reengineering the translational research enterprise [1][2][3]. Although most institutions recognize the need for growing research informatics support, reductions in grant funding and restricted institutional budgets have diminished the ability of many clinical organizations to hire and retain operations-focused CRI faculty and staff [4,5]. Consequently, limited personnel and resources are stretched to support research needs, forcing sites to restrict programs and services and limit innovation [6][7][8][9]. ...
The Research Electronic Data Capture (REDCap) data management platform was developed in 2004 to address an institutional need at Vanderbilt University, then shared with a limited number of adopting sites beginning in 2006. Given bi-directional benefit in early sharing experiments, we created a broader consortium sharing and support model for any academic, non-profit, or government partner wishing to adopt the software. Our sharing framework and consortium-based support model have evolved over time along with the size of the consortium (currently more than 3200 REDCap partners across 128 countries). While the "REDCap Consortium" model represents only one example of how to build and disseminate a software platform, lessons learned from our approach may assist other research institutions seeking to build and disseminate innovative technologies.
... Dedicated academia or dedicated research organisations can only work for effective translational research. 6,7 One study estimated that it requires 17 years for only 14% of new scientific discoveries to become incorporated into standard practice. 8 The translational science spectrum is shown in figure 2. (T1 and T2), 4 stage model (T1, T2, T3, and T4), and 5 stage model (T1, T2, T3, T4, and T5). 10 In two-stage model, T1 research refers to the bench to bedside meaning translating knowledge from the basic sciences into the development of new intervention and T2 research reflects translating the findings from clinical trials into day by day practice." ...
p>The concept of translational research is emerging around the globe. The practice of clinical care, health promotion and health care delivery system need to be evidence based. Translational research is the utmost solution to generate evidence and implement the scientific findings. Now the time has come to conduct translational research in Nepal to generate our own evidence and to integrate it into the policy of new federal health system. The objective of this review article was to identify status, challenges and future strategies of translational research in Nepal.</p
... between clinical, translational and basic science investigators; limited implementation of interdisciplinary research, including lack of team science credentials in the academic promotion process, insufficient research funding, and challenges related to the balance of clinical care and research responsibilities among physician scientists. [4][5][6] Translation of scientific advances to improve health in the community is unacceptably slow. 3 7 For example, a recent review of the literature showed that studies report an average of 17 years is required for specific positive research evidence to be implemented into clinical practice. ...
A major impediment to improving the health of communities is the lack of qualified clinical and translational research (CTR) investigators. To address this workforce shortage, the National Institutes of Health (NIH) developed mechanisms to enhance the career development of CTR physician, PhD, and other doctoral junior faculty scientists including the CTR-focused K12 program and, subsequently, the KL2-mentored CTR career development program supported through the Clinical and Translational Science Awards (CTSAs). Our evaluation explores the impact of the K12/KL2 program embedded within the Atlanta Clinical and Translational Science Institute (ACTSI), a consortium linking Emory University, Morehouse School of Medicine and the Georgia Institute of Technology. We conducted qualitative interviews with program participants to evaluate the impact of the program on career development and collected data on traditional metrics (number of grants, publications). 46 combined K12/KL2 scholars were supported between 2002 and 2016. 30 (65%) of the 46 K12/KL2 scholars are women; 24 (52%) of the trainees are minorities, including 10 (22%) scholars who are members of an underrepresented minority group. Scholars reported increased research skills, strong mentorship experiences, and positive impact on their career trajectory. Among the 43 scholars who have completed the program, 39 (91%) remain engaged in CTR and received over $89 000 000 as principal investigators on federally funded awards. The K12/KL2 funding provided the training and protected time for successful career development of CTR scientists. These data highlight the need for continued support for CTR training programs for junior faculty.
... El hospital se constituye así en el núcleo fundamental que integra diversos espacios institucionales y componentes de áreas y disciplinas en la tendencia reciente de la investigación clínica concebida desde la investigación translacional. Este nuevo campo y visión de perspectiva de la investigación en la biomedicina genera un reto organizacional importante en cuanto a la integración de investigadores, instituciones y disciplinas (Hörig & Pullman, 2004;Lehmman et al., 2003;Littman et al., 2007;Loannidis, 2004;Neuhauser & Pober, 2001;Sontag, 2005;Wang & Falus, 2005;Zerhouni, 2005). ...
... Establishing ability-based trust is important in translational medical teams that often must overcome implicit power differentials between professions, which potentially hinder transdisciplinary efforts. Academic cultures often deter collaboration between multidisciplinary investigators, as it favors departmental efforts over interdisciplinary programs [56], and this hurts collaborative efforts. By sharing ones' background and expertise with the team and highlighting their unique contribution to the team it serves to reduce power concerns and reduce the culture of inhibition and restraint in communication associated with it. ...
... Establishing ability-based trust is important in translational medical teams that often must overcome implicit power differentials between professions, which potentially hinder transdisciplinary efforts. Academic cultures often deter collaboration between multidisciplinary investigators, as it favors departmental efforts over interdisciplinary programs [56], and this hurts collaborative efforts. By sharing ones' background and expertise with the team and highlighting their unique contribution to the team it serves to reduce power concerns and reduce the culture of inhibition and restraint in communication associated with it. ...
... This approach is particularly interesting from an economical point of view because these drugs are already approved. This saves time and money in clinical trials and in translation of the research into an industrial product, which can be a limiting point in new drug release (Pober et al., 2001). Besides the pharmaceutical approach, additional therapeutic approaches techniques were developed and tested in GRDM (Benedetti et al., 2013) and human patients (Kinali et al., 2009). ...
The numerous advantages of zebrafish were used to study two hereditary diseases: desminopathy and pulmonary veno-occlusive disease (PVOD). Desminopathy is a myofibrillar myopathy characterized by the presence of granulofilamentous aggregates. Two models of loss and gain of function of desmin showed the implication of both loss of functional desmin and presence of desmin aggregates in desminopathy clinical manifestations. Phenotypes observed in these models include in particular a perturbation of the heart contraction biomechanics and of calcium propagation throughout the myocardium. Potential drugs, lowering the aggregate content, were proposed. After validating the use of zebrafish as a model of arterial hypertension, by verifying the implication of the elasticity of the aorta in blood flow regulation, we generated and characterized PVOD models. PVOD is a rare and severe form of pulmonary hypertension. The venous-specificity of the phenotypes observed in this pathology was confirmed.
... Lord et al. [26] and de Bono [27] argue that cancer biologists do not have the same understanding of what constitutes a feasible target or a thorough understanding of clinical issues as clinicians, but nevertheless should have a crucial role in the design and analysis of clinical trials. Pober et al. [28] argue that, traditionally, the responsibility for making the connection between laboratory and clinic has fallen on the cliniciansresearchers. However, due to difficulties in recruiting and maintaining statutory physicians-researchers with both clinical and basic science training, creating translational research teams with clinicians and laboratory-based investigators is a viable solution. ...
Background
In a context where there is an increasing demand to evaluate the outcome of bio-medical research, our work aims to develop a set of indicators to measure the impact of translational cancer research. The objective of our study was to explore the scope and issues of translational research relevant to evaluation, explore the views of researchers on the evaluation of oncological translational research, and select indicators measuring the outcomes and outputs of translational research in oncology by consensus.Methods
Semi-structured interviews amongst 23 researchers involved in translational cancer research were conducted and analysed using thematic analysis. A two-round modified Delphi survey of 35 participants with similar characteristics was then performed followed by a physical meeting. Participants rated the feasibility and validity of 60 indicators. The physical meeting was held to discuss the methodology of the new indicators.ResultsThe main themes emerging from the interviews included a common definition for translational research but disagreements about the exact scope and limits of this research, the importance of multidisciplinarity and collaboration for the success of translational research, the disadvantages that translational research faces in current evaluation systems, the relative lack of pertinence of existing indicators, and propositions to measure translational cancer research in terms of clinical applications and patient outcomes. A total of 35 participants took part in the first round survey and 12 in the second round. The two-round survey helped us select a set of 18 indicators, including four that seemed to be particularly adapted to measure translational cancer research impact on health service research (number of biomarkers identified, generation of clinical guidelines, citation of research in clinical guidelines, and citation of research in public health guidelines). The feedback from participants helped refine the methodology and definition of indicators not commonly used.Conclusion
Indicators need to be accepted by stakeholders under evaluation. This study helped the selection and refinement of indicators considered as the most relevant by researchers in translational cancer research. The feasibility and validity of those indicators will be tested in a scientometric study.
... Second, the endeavor is exceptionally challenging [11][12][13][14][15][16][17]. This aspect should not be minimized. ...
Advances in biology are occurring at a breathtaking pace today, from genetic insights facilitated by the Human Genome Project and next generation DNA sequencing technologies, to global nucleic acid and proteomic expression measurement using new high-throughput methods. Less publicized in recent years, yet still the central driver of progress, are the steadily proceeding biological insights gained through tried and true hypothesis-driven investigation into the complex worlds of metabolism, growth, development, and regulation. Certainly, the basic science ecosystem is productive and this portends well for the myriad new applications that will benefit mankind; drugs, vaccines, devices, and related economic growth—
or perhaps not
—in stark contrast to the generation of fundamental biological knowledge are inefficiencies in applying this information to real-world problems, especially those of the clinic. While investigation hums along at light speed, translation often does not. The good news is that obstacles to progress are tractable. The bad news, however, is that these problems are difficult. The present paper examines translational research from multiple perspectives, beginning with a historical account and proceeding to the current state of the art. Included are descriptions of successes and challenges, along with conjecture on how the field may need to evolve in the future.
... However, there is little information on how to create collaborations initially. Researchers have suggested forming interdisciplinary collaborative teams and examining research questions that require expertise in several different domains (Pober, Neuhauser, & Pober, 2001). Investigators wishing to create research collaborations should consider the needs of their community, the needs of their university, and the ways in which their research team can satisfy those needs. ...
Research and assessment skills are important competencies for psychologists to possess regardless of their professional role. Participating in collaborative research during graduate training is an effective way for graduate students to gain a diversity of experiences in these areas. The current work describes the training opportunities in a collaborative research project examining mental health effects of the Gulf Oil Spill on Mississippi coastal residents. An additional function of this collaborative research project was to assess the mental health services provided in the context of the spill. The purpose of this article is to emphasize the opportunities that accompany exposure to methodological issues associated with collaborative research, as well as experience with public health administration (i.e., provision of psychological services). In addition, we emphasize the importance of having an understanding of the real-world implications of collected data (e.g., via presentations, publications, and agency reports). Suggestions are offered with respect to the incorporation of such experiences into graduate training curricula.
... The author explains translational research as a "bench-to-bedside" enterprise, tying together knowledge from basic sciences with the intent of producing new drugs, devices, and treatment options for patients." Mentorship is considered very important within translational research, since this collaborative design has different rules and challenges (Pober et al., 2001). ...
Objective:This dissertation developed an automatic classification procedure, as an example of a novel tool for an informationist, which extracts information from published abstracts, classifies abstracts into their "fields of study," and then determines the researcher's "field of study" and "level of activity." Method: This dissertation compared a domain expert's method of classification and an automatic classification procedure on a random sample of 101 medical researchers (derived from a potential list of 305 medical researchers) and their associated abstracts. Design: The study design is a retrospective, cross-sectional, inter-rater agreement study, designed to compare two classification methods (i.e., automatic classification procedure and domain expert). The study population consists of University of Pittsburgh, School of Medicine, Department of Medicine (DOM) professionals who (1) have published at least one article listed in PubMed® as first or last author and/or (2) are the primary investigator for at least one grant listed in CRISP.Main outcome measures: Three outcome measures were derived from the domain expert's versus automatic categorization procedure: (1) an abstract's "field of study," (2) a researcher's "field of study" and (3) a researcher's "level of activity and field of study." Results: Kappa showed moderate agreement between automatic and domain expert classification for the abstracts' "field of study" (Kappa = 0.535, n = 504, p < .000). Kappa showed moderate agreement between automatic and domain expert classification of the researcher's "field of study" (Kappa = 0.535, n = 101, p < .000). Kappa showed good agreement between automatic and domain expert classification of the researcher's "level of activity and field of study" (Kappa = 0.634, n = 101, p < .000). Conclusion: The study suggests that an automatic library classification procedure can provide rapid classification of medical research abstracts into their "fields of study." The classification procedure can also process multiple abstracts' "fields of study" and classify their associated medical researchers into their "field of study" and "level of activity and field of study." The classification procedure, used as a tool by an informationist, can be used as the basis for new services.
This study explores the role of academic research in preserving, nurturing, and adapting Islamic culture amidst the challenges of globalization, modernization, and sociopolitical changes. It focuses on three key research questions: how academic research preserves Islamic values, addresses challenges posed by modernity, and promotes inclusive multiculturalism while maintaining core Islamic principles. Findings from the literature highlight the integration of Islamic values into modern education, the alignment of professional practices with Islamic ethics, and the use of technology to preserve and promote Islamic traditions. Case studies from Egypt, Indonesia, Malaysia, and Nigeria demonstrate the success of these strategies, such as redesigning curricula to incorporate Islamic moral teachings, embedding Shariah-compliant principles into banking systems, and fostering digital platforms to engage younger generations. The study contextualizes these findings for Afghanistan, emphasizing the need for research-driven reforms in education, professional sectors, and cultural preservation initiatives. Recommendations include modernizing Afghan educational curricula, adopting ethical frameworks for finance and healthcare, and developing localized digital platforms to document and disseminate Islamic traditions. By implementing these strategies, Afghanistan can address the challenges posed by globalization and modernization, ensuring the sustainability of its Islamic identity while fostering social cohesion.
The development of a telehealth technology in an academic setting is a complex project that faces several obstacles. The early assessment of the project risks plays a critical role in the translation of promising telehealth innovations into healthcare practice. This paper presents a decision support tool based on Failure Mode and Effects Analysis (FMEA) and Quality Function Deployment (QFD) techniques to associate the project risks to relevant success factors. Certain modifications in both techniques are applied to deploy them for project risk assessment. The project risks and success factors used in the tool are identified from the literature. The proposed decision support tool enables researchers to manage the risks in their telehealth development projects and identify action items to overcome such risks. The application of the proposed tool is illustrated with a telehealth development project for virtual physical therapy.
In recent years, nonprofit firms focused on specific diseases have increased their grantmaking efforts in the search of a cure. They have become more aggressive in directly funding research and lobbying for public support, even if their cause affects a small number of people. This paper contributes to the literatures on R&D financing by developing the first production function for disease and medical research nonprofits, a growing funder of biomedical R&D. Using IRS data, the model estimates the role of market competition and firm demographics on the adoption of grantmaking and lobbying strategies. Most notably, results provide evidence that firms in more geographically concentrated (less competitive markets) are more likely to adopt a lobbying strategy and less likely to be grantmaking on the extensive margin. Descriptive cases also illustrate funding discrepancies between charitable and government support across disease prevalence.
In this article, I describe how gender bias can affect the design, testing, clinical trials, regulatory approval, and clinical use of implantable devices. I argue that bad outcomes experienced by women patients are a cumulative consequence of small biases and inattention at various points of the design, testing, and regulatory process. However, specific instances of inattention and bias can be difficult to identify, and risks are difficult to predict. This means that even if systematic gender bias in implant design is an ethical issue, it is one with no clearly blameworthy player. From a practical perspective, there is no single obvious point at which to intervene. Philosophers working in other areas have explored structurally similar moral problems—sometimes referred to as “moral aggregation problems”—such as the type of environmental harm caused by small actions of many players. I describe key features of these type of problems and strategies to address them. I then draw on these to suggest an approach to gender bias in medical implant design and use.
The 2018 BMES Cellular and Molecular Bioengineering (CMBE) Conference was organized around the theme of Discovering the Keys: Transformative and Translational Mechanobiology. The conference programming included a panel discussion on Translating Mechanobiology to the Clinic. The goal of the panel was to initiate a dialogue and share pearls of wisdom from participants’ successes and failures in academia and in industry toward translating scientific discoveries in mechanobiology to technology products in the market or toward devices or drugs that impact clinical care. This commentary reviews the major themes and questions discussed during the panel, including defining translational research and how it applies to mechanobiology, the current landscape in translational mechanobiology, the process for translating mechanobiology research, challenges in translating mechanobiology research, and unique opportunities in translating mechanobiology research.
Lengthy review times for institutional review boards (IRBs) are a well-known barrier to research. In response to numerous calls to reduce review times, we devised “Real-Time IRB,” a process that drastically reduces IRB review time. In this, investigators and study staff attend the IRB meeting and make changes to the protocol while the IRB continues its meeting, so that final approval can be issued at the meeting. This achieved an overall reduction in time from submission to the IRB to final approval of 40%. While this process is time and resource intensive, and cannot address all delays in research, it shows great promise for increasing the pace by which research is translated to patient care.
Translational research (TR) can be viewed as a prominent concept that reflects expectations of societal relevance and has become an important issue in science policy. This article analyses the framings of TR in the policy discourse by comparing policy papers in the USA and some European countries. Problem frames in favor of TR are interpreted as expressions of specific conceptions of science, being either organizational or professional. Based on a qualitative content analysis, different policy documents relating to TR between 2003 and 2013 in the USA and Europe are compared. I found that TR in the USA is more strongly framed as a professional problem whereas in Europe, TR is framed as an organizational problem. It is argued that these different framings of TR have consequences for conceptions of societal relevance and steering in TR.
Translational research facilitates the application of basic scientific discoveries in clinical and community settings to prevent and treat human diseases. The translation of knowledge and innovations from basic laboratory experiments to point-of-care patient applications; production of new drugs, devices, and healthcare products; and promising treatments for patients is referred to as benchside to bedside transition. Numerous opportunities encompass translational research. However, there are several obstacles involved in the process that make the translational journey quite challenging. The major challenges
that hamper the growth of translational research include insufficient resources, inadequate funding and infrastructure, shortage of qualified researchers, and lack of sufficient experience in essential techniques. Translational drug discovery and development is an exceedingly difficult, expensive, time-consuming, and risky process. Despite thousands of pharmaceutical companies working to develop and get new drugs to market, and billions of dollars spent every year, only a few new molecular entities (NMEs) receive marketing approval from the FDA per year. Translational drug discovery demands both the need for cooperation between clinical and pharmacological research and the significance of the role of academia in target identification and drug discovery, design, and development. This chapter highlights an overview of translational research in a drug discovery and development perspective. We further discussed associated opportunities and challenges, as well as possible strategies that could be used to overcome the challenges. Certain strategies like prioritizing research area, clearer vision on the project, committed team of researchers, established infrastructure, sufficient funding, and meaningful collaborations could be highly beneficial in accelerating the hunt to discover new drugs and for the establishment of successful translational drug discovery process.
Translational research plays a crucial role in bridging the gap between fundamental and clinical research. The importance of integrating research training into medical education has been emphasized. Predictive factors that help to identify the most motivated medical students to perform academic research are unknown. In a cross-sectional study on a representative sample of 315 medical students, residents and attending physicians, using a comprehensive structured questionnaire we assessed motivations and obstacles to perform academic research curricula (ie, research initiation fellowship, Master 1, Research Master 2, and PhD). Independent predictive factors associated with high "motivation score" (top quartile on motivation score ranging from 0 to 10) to enroll in academic research curricula were derived using multivariate logistic regression analysis. Independent predictors of high motivation score for performing Master 1 curriculum were: "considering that the integration of translational research in medical curriculum is essential" (OR, 3.79; 95% CI, 1.49-9.59; P = 0.005) and "knowledge of at least 2 research units within the university" (OR, 3.60; 95% CI, 2.01-6.47; P < 0.0001). Independent predictors of high motivation score for performing Research Master 2 curriculum were: "attending physician" (OR, 4.60; 95% CI, 1.86-11.37; P = 0.001); "considering that the integration of translational research in medical curriculum is essential" (OR, 4.12; 95% CI, 1.51-11.23; P = 0.006); "knowledge of at least 2 research units within the university" (OR, 3.51; 95% CI, 1.91-6.46; P = 0.0001); and "male gender" (OR, 1.82; 95% CI, 1.02-3.25; P = 0.04). Independent predictors of high motivation score for performing PhD curriculum were: "considering that the integration of translational research in medical curriculum is essential" (OR, 5.94; 95% CI, 2.33-15.19; P = 0.0002) and "knowledge of at least 2 research units within the university" (OR, 2.63; 95% CI, 1.46-4.77; P = 0.001). This is the first study that has identified factors determining motivations and barriers to carry out academic research curricula among undergraduate and postgraduate medical students. Improving these 2 areas will certainly have an impact on a better involvement of the next generation of physicians in translational medicine.
The pace of technological innovation, the complex clinical research enterprise and increased public expectation for health benefits has led to the adoption of a new strategy of research inquiry: translational science. This model aims to encourage a team-based, interdisciplinary approach to patient oriented research by increasing the efficiency by which discoveries are implemented to clinical practice. The goals of translational science require a shift of perspective from traditional approaches to research ethics to that of a more humanistic framework. The core of this re-interpretation is the claim that the mere application of formal rules, codes, regulatory procedures, and ethical principles undermines and even ignores the moral content of the practice of translational science. Rather, translational ethics draws on humanities approaches to integrate relationship building, interdisciplinarity and narrative interpretation within a multidisciplinary, team-based setting. In this way, ethical values and norms are generated, experienced and shared through relationships, dialogue, reflection, and support. By adopting this humanistic framework, the translational ethicist seeks to broaden the ethical competence of translational scientists, deepen understanding of the subjective experiences of research participants, and enlarge the capacity and sustainability of trust within research institutions and the communities they serve. By integrating the values common to both science and ethics and aligning the aspirations at the core of these human endeavors, researchers and ethicists strive together to improve the practice of science. © Common Ground, Jeffrey S. Farroni, Michele A. Carter, All Rights Reserved.
Translational medicine bridges the gap between discoveries in biomedical science and their safe and effective clinical application. Despite the gross opportunity afforded by modern research for unparalleled advances in this field, the process of translation remains protracted. Efforts to expedite science translation have included the facilitation of interdisciplinary collaboration within both academic and clinical environments in order to generate integrated working platforms fuelling the sharing of knowledge, expertise, and tools to align biomedical research with clinical need. However, barriers to scientific translation remain, and further progress is urgently required. Collective intelligence and crowdsourcing applications offer the potential for global online networks, allowing connection and collaboration between a wide variety of fields. This would drive the alignment of biomedical science with biotechnology, clinical need, and patient experience, in order to deliver evidence-based innovation which can revolutionize medical care worldwide. Here we discuss the critical steps towards implementing collective intelligence in translational medicine using the experience of those in other fields of science and public health. Key messages The scientific translation of biomedical research into clinical applications is protracted, despite the mass opportunity afforded by modern science. Barriers to translational medicine exist as a result of the impracticalities of research, organizational hurdles, and lack of an interdisciplinary workforce. Collective intelligence and crowdsourcing offer the potential to expedite the translational process by providing a platform upon which interdisciplinary workforces can communicate and collaborate, aligning biomedical research with clinical need revolutionizing health care worldwide.
The incorporation of full-time researchers into hospitals has been identified as one of the strategies to bridge the so-called bed-bench gap and foster translational research. This paper explores the extent to which the incorporation of researchers into Spanish public hospitals helped to foster translational research. We examine the FIS (Fondo de Investigación Sanitaria [Health Research Fund])/Miguel Servet Programme's contribution to the three factors that characterize translational research: first, the relationship between clinical and basic researchers; secondly, the transfer of scientific knowledge from basic research to clinical practice; and thirdly, the generation of biomedical research questions based on clinical practice. Data were obtained through a survey of researchers, research group leaders, and heads of departments and centres where these researchers worked. The results show how public policy actions to provide human resources in R&D, which are specifically targeted to incorporate basic researchers within the essentially clinical hospital environment, may play a valuable role in promoting translational research. ©The Author 2012. Published by Oxford University Press. All rights reserved.
This article aims to define the major trends currently affecting space needs for academic medical center (AMC) cancer centers. It will distinguish between the trends that promote the concentration of services with those that promote decentralization as well as identify opportunities for achieving greater effectiveness in cancer care space planning.
Changes in cancer care-higher survival rates, increased clinical trials, new technology, and changing practice models-increasingly fill hospitals' and clinicians' schedules and strain clinical space resources. Conflicts among these trends are concentrating some services and dispersing others. As a result, AMCs must expand and renovate intelligently to continue providing state-of-the-art, compassionate care.
Although the typical AMC cancer center can expect to utilize more space than it would have 10 years ago, a deeper understanding of the cancer center enterprise can lead to opportunities for more effectively using available facility resources. Each AMC must determine for itself the appropriate balance of patient volume, clinical activity, and services between its main hospital campus and satellite branches. As well, space allocation should be flexible, as care trends, medical technology, and the provider's own priorities shift over time. The goal isn't necessarily more space-it's better space.
© The Author(s) 2015.
Despite its growing popularity in the biomedical literature, the particular phenomenon of translational research management has not been addressed from an organizational and strategic perspective yet. Our study aims to fill this gap by identifying a set of managerial practices that could influence how knowledge is created, amplified and transferred from biomedical research both to clinical practice and the productive sector. As a result of the theoretical review, we have proposed a preliminary model to guide our empirical work. We have developed an exploratory case study to gather organisational information from an outstanding translational research center. The results obtained from the analysis have allowed us to build an induced model of managerial practices that both affect the creation, integration and transfer of knowledge in the translational research organization studied, as well as derives a set of research propositions. Finally, we present the main academic and managerial implications of the work, together with its limitations and related future research lines.
El proyecto “El investigador a tiempo completo como figura determinante en el desarrollo de la actividad investigadora en los hospitales. El caso de los investigadores del Programa de Contratos de Investigadores en el Sistema Nacional de Salud (SNS)”, realizado por el Grupo ETC con el apoyo económico del Instituto de Salud Carlos III, tiene como finalidad realizar un seguimiento y evaluación del Programa de Contratos de Investigadores en el SNS “Miguel Servet”. Desde 2007, año en que finalizaron sus seis años de contrato los investigadores de la cuarta convocatoria, se ha venido realizando un seguimiento de la actividad desarrollada por los investigadores incorporados al programa y una evaluación expost de los resultados de éste (Rey Rocha y col., 2010, 2012), con el objetivo de analizar hasta qué punto se han cumplido sus objetivos, de identificar sus debilidades y fortalezas y finalmente de contribuir a la comprensión de los elementos determinantes de su eventual éxito y de valorar en qué medida la incorporación de estos investigadores ha contribuido a potenciar la investigación en los centros del SNS. Por otra parte, el estudio ha permitido testar una serie de hipótesis de investigación relevantes en el área de los estudios de la Ciencia y la Tecnología, concretamente en el ámbito de la investigación biomédica y en salud. Dos de las líneas de investigación más relevantes dentro de este proyecto se refieren al estudio del papel de los investigadores como promotores de la innovación y de la generación de contextos favorables para la investigación traslacional en el sector sanitario público. Esta línea de investigación incorpora el estudio de las variables contextuales que determinan las condiciones de trabajo en las que se desenvuelven los investigadores en el centro receptor, incluyendo variables de tipo social y psicosocial como el clima organizacional, el grado de independencia y autonomía, la disponibilidad de recursos, las relaciones que se establecen entre los distintos componentes del sistema, o las incertidumbres generadas en relación con las expectativas de estabilidad y promoción de los investigadores. Tras un primer ejercicio de evaluación y seguimiento centrado en las cuatro primeras convocatorias del programa (1998-2001), la actualización del estudio mediante la incorporación de información referente a las convocatorias 2002-2005 ha permitido analizar el desarrollo del Programa FIS/Miguel Servet con una mayor perspectiva temporal, a la vez que obtener indicadores de actividad científica más robustos, continuando así en la línea de incorporar la evaluación como herramienta de trabajo en la planificación estratégica de la investigación biomédica.
Reperfusion of ischaemic tissues is often associated with microvascular dysfunction that is manifested as impaired endothelium-dependent dilation in arterioles, enhanced fluid filtration and leukocyte plugging in capillaries, and the trafficking of leukocytes and plasma protein extravasation in postcapillary venules. Activated endothelial cells in all segments of the microcirculation produce more oxygen radicals, but less nitric oxide, in the initial period following reperfusion. The resulting imbalance between superoxide and nitric oxide in endothelial cells leads to the production and release of inflammatory mediators (e.g. platelet-activating factor, tumour necrosis factor) and enhances the biosynthesis of adhesion molecules that mediate leukocyte-endothelial cell adhesion. Some of the known risk factors for cardiovascular disease (hypercholesterolaemia, hypertension, and diabetes) appear to exaggerate many of the microvascular alterations elicited by ischaemia and reperfusion (I/R). The inflammatory mediators released as a consequence of reperfusion also appear to activate endothelial cells in remote organs that are not exposed to the initial ischaemic insult. This distant response to I/R can result in leukocyte-dependent microvascular injury that is characteristic of the multiple organ dysfunction syndrome. Adaptational responses to I/R injury have been demonstrated that allow for protection of briefly ischaemic tissues against the harmful effects of subsequent, prolonged ischaemia, a phenomenon called ischaemic preconditioning. There are two temporally and mechanistically distinct types of protection afforded by this adaptational response, i.e. acute and delayed preconditioning. The factors (e.g. protein kinase C activation) that initiate the acute and delayed preconditioning responses appear to be similar; however the protective effects of acute preconditioning are protein synthesis-independent, while the effects of delayed preconditioning require protein synthesis. The published literature in this field of investigation suggests that there are several potential targets for therapeutic intervention against I/R-induced microvascular injury.
Arterial inflammatory responses are thought to be a significant component of atherosclerotic disease. We describe here, using a transgenic approach, the mutual perpetuation of immune-mediated arterial inflammation and cholesterol-induced atherosclerosis. Mice expressing the bacterial transgene beta-galactosidase exclusively in cardiomyocytes and in smooth muscle cells in lung arteries and the aorta (SM-LacZ), and hypercholesterolemic apolipoprotein E-deficient SM-LacZ mice (SM-LacZ/apoE(-/-)) developed myocarditis and arteritis after immunization with dendritic cells presenting a beta-galactosidase-derived immunogenic peptide. Hypercholesterolemia amplified acute arteritis and perpetuated chronic arterial inflammation in SM-LacZ/apoE(-/-) mice, but had no major impact on acute myocarditis or the subsequent development of dilated cardiomyopathy. Conversely, arteritis significantly accelerated cholesterol-induced atherosclerosis. Taken together, these data demonstrate that the linkage of immune-mediated arteritis and hypercholesterolemia favors initiation and maintenance of atherosclerotic lesion formation. Therapeutic strategies to prevent or disrupt such self-perpetuating vicious circles may be crucial for the successful treatment of atherosclerosis.
Organ shortage and suboptimal prosthetic or biological materials for repair or replacement of diseased or destroyed human organs and tissues are the main motivation for increasing research in the emerging field of tissue engineering. No organ or tissue is excluded from this multidisciplinary research field, which aims to provide vital tissues with the abilities to function, grow, repair, and remodel. There are several approaches to tissue engineering, including the use of cells, scaffolds, and the combination of the two. The most common approach is biodegradable or resorbable scaffolds configured to the shape of the new tissue (e.g. a heart valve). This scaffold is seeded with cells, potentially derived from either biopsies or stem cells. The seeded cells proliferate, organize, and produce cellular and extracellular matrix. During this matrix formation, the starter matrix is degraded, resorbed, or metabolized. First clinical trials using skin or cartilage substitutes are currently under way. Both the current state of the field and future prospects are discussed.
To describe the characteristics of thrombus formation on atherosclerotic plaques, the clinical expression of atherothrombosis in vascular disease, and some of the most recent therapeutic approaches in cardiovascular disease.
MEDLINE search for English-language articles on thrombosis and atherosclerosis published up to January 2000. Abstracts of recent international meetings on new aspects of thrombus formation and new therapeutic options were reviewed, and references from identified articles were selected and reviewed.
Experimental, basic, clinical, and epidemiologic studies related to the pathophysiology of thrombosis on atherosclerotic lesions. Therapeutic approaches were obtained from experimental studies and large clinical investigations.
Arterial vessel wall substrate, rheologic conditions, and blood thrombogenicity influence the process of thrombus formation in arteries. Thrombus formation on disrupted atherosclerotic plaques or arterial erosions frequently causes acute coronary syndromes. Severe atherosclerosis of the aorta has been identified as an important morphologic indicator of an increased risk for thromboembolism. Current antithrombotic therapies available as long-term treatment for patients with cardiovascular disease are often not effective enough to prevent acute thrombotic events and deterioration of atherosclerosis.
Improved understanding of the pathophysiology of thrombus formation on atherosclerotic plaques has led to the development of new therapeutic approaches. Glycoprotein IIb/IIIa, tissue factor, factor Xa, and thrombin inhibitors as well as combined antithrombotic therapy, such as aspirin plus a thienopyridine plus warfarin, are being evaluated as new possible options for the treatment of arterial thrombosis.
Long-term treatment with potent antithrombotic drugs, such as tissue factor or factor Xa inhibitors, that effectively block thrombosis without causing bleeding complications could help reduce death from cardiovascular disease.
The scholarship of integration is concerned with making connections across scientific disciplines, placing the work of individual investigators and their specialty fields into a larger context, and educating nonspecialists. The authors focus their comments on the biomedical sciences, but observe that closer integration of the biomedical and behavioral sciences will be particularly crucial to advance understanding of the human brain. They observe that as biomedical sciences become more technologically sophisticated, progress is increasingly dependent on sciences such as physics, chemistry, engineering, and related fields. However, the scholarship of integration has been slower than other forms of scholarship to gain acceptance as an integral activity of the professoriate. The isolation of disciplines from one another, particularly at large universities, and the perception of interdisciplinary work as risky and professionally unrewarding are among the forces that may discourage integrative scholarship. In addition, a troubling disconnect exists between the scientific community and the larger public in the understanding of science. Leaders in academic medicine and science must develop strategies to move interdisciplinary work from the margins into the mainstream of academia. Solutions that have been proposed include creating new research entities and funding mechanisms dedicated to interdisciplinary work; reinvigorating the integrative role of the physician-scientist; and training specialists in translational research. The scientific community must also work to develop more effective means of communicating the importance of its work to the public.
The advanced lesions of atherosclerosis represent the culmination of a specialized form of chronic inflammation followed by a fibroproliferative process that takes place within the intima of the affected artery. Proliferation of smooth muscle cells and generation of connective tissue occur. Proliferation results from interactions between arterial smooth muscle, monocyte-derived macrophages, T lymphocytes, and endothelium. The initial lesion of atherosclerosis, the fatty streak, begins as an accumulation of monocytederived macrophages and T lymphocytes, which adhere and migrate into the intima of the affected artery. Smooth muscle cells, which are present in the intima or which migrate into the intima from the media, then replicate. Monocyte-derived macrophages and T cells also replicate during lesion formation and progression due to the production of cytokines and growth-regulatory molecules. These molecules determine whether there is proliferation and lesion progression or inhibition of proliferation and lesion regression. Several growthregulatory molecules may play critical roles in this process, including platelet-derived growth factor (PGDF), transforming growth factor beta, fibroblast growth factor, heparinbinding epidermal growth factor-like growth factor, and others. PDGF may be one of the principal components in this process because protein containing the PDGF B-chain has been demonstrated within activated lesion macrophages during every phase of atherogenesis. The presence of this growth factor and its receptors on lesion smooth muscle cells creates opportunities for smooth muscle chemotaxis and replication. Smooth muscle proliferation depends upon a series of complex signals based upon cellular interactions in the local microenvironment of the artery. The intracellular signalling pathways for mitogenesis versus chemotaxis are being investigated for smooth muscle. The roles of the cytokines and growth-regulatory peptides involved in these cellular interactions represent critical points of departure for intervention and the development of new diagnostic methods. In addition, magnetic resonance imaging has been developed to demonstrate the fine structure of lesions of atherosclerosis in peripheral arteries not subject to cardiac motion. This noninvasive methodology holds great promise for the future of these approaches.
Context.
—Interest in clinical investigative careers has declined over the past 2 decades. While several factors are likely involved in this decline, one is the perceived difficulty in obtaining support for investigator-initiated clinical research projects.
Recent discoveries of endogenous negative regulators of angiogenesis, thrombospondin, angiostatin and glioma-derived angiogenesis inhibitory factor, all associated with neovascularized tumours, suggest a new paradigm of tumorigenesis. It is now helpful to think of the switch to the angiogenic phenotype as a net balance of positive and negative regulators of blood vessel growth. The extent to which the negative regulators are decreased during this switch may dictate whether a primary tumour grows rapidly or slowly and whether metastases grow at all.
The late complications of diabetes represent in large part microvascular dysfunction. The development of techniques to measure microvascular function has resulted in a clearer picture of the stages of development of microangiopathy and the key pathophysiological processes involved. Considerable evidence supports the hemodynamic hypothesis of pathogenesis, which argues that early insulin-dependent diabetes is characterized by increased microvascular pressure and flow. Resultant injury to the microvascular endothelium causes adaptive microvascular sclerosis contributing to a loss of vasodilatory reserve and autoregulatory capacity with increasing disease duration. High susceptibility to microangiopathy appears to be characterized by both high capillary pressure and increased permeability, although the interrelationship between these variables needs to be better defined. In normotensive non-insulin-dependent diabetes subjects, a different pattern of microvascular functional abnormalities is apparent; it is hypothesized that these differences represent the impact of a prediabetic insulin-resistant phase on microvascular behavior and may in part explain the differential expression of vascular pathology in the two major types of diabetes. The physiological framework that has been defined reveals those pivotal processes upon which scientific attention should be centered and facilitates the generation of plausible molecular and cellular mechanisms that fit the physiological facts.
The future viability of academic medical centers is threatened. These institutions have flourished since the 1960s, even managing to survive the shift toward prospective payment over the past decade, but many are now in danger of becoming seriously compromised. In battles for the rapidly expanding number of managed-care patients, and in vigorous competition with nonacademic hospitals, teaching hospitals and their faculty-practice plans are being forced to negotiate bargain-basement rates of payment. In fact, they are often forced to price services below cost. In response to these pressures, many have reduced the number of faculty members and other personnel.1 At present, . . .
Despite their widespread use in patients with acute myocardial infarction, all currently available thrombolytic agents suffer from a number of significant limitations, including resistance to reperfusion, the occurrence of acute coronary reocclusion and bleeding complications. Therefore, the quest for thrombolytic agents with a higher thrombolytic potency, specific thrombolytic activity and/or a better fibrin-selectivity continues. Several lines of research towards improvement of thrombolytic agents are being explored, including the construction of mutants and variants of plasminogen activators, chimeric plasminogen activators, or plasminogen activators from animal or bacterial origin. Several of these new thrombolytic agents have been evaluated in animal models of venous or arterial thrombosis, some in pilot studies in patients with acute myocardial infarction and a few in large clinical trials with mortality end points. Definition of their relative therapeutic benefit, against presently available "classical" thrombolytic agents will require further dose-finding studies and randomized clinical trials.
Interest in clinical investigative careers has declined over the past 2 decades. While several factors are likely involved in this decline, one is the perceived difficulty in obtaining support for investigator-initiated clinical research projects.
To analyze the priority scores and funding rates of patient-oriented research (POR) compared with laboratory-oriented research (LOR) when grant applications to the National Institutes of Health (NIH) are reviewed by study sections of the NIH Division of Research Grants.
Research grant applications submitted to NIH were classified by the applicant as involving human subjects or not (LOR). Those classified as involving human subjects were divided into clinical (POR) and nonclinical research. The association of priority score and POR or LOR status was evaluated using chi2 statistical techniques.
Twelve thousand investigator-initiated grant applications (RO1s) in 2 of the 1994 NIH review cycles.
Grant application priority scores and funding rates.
On the basis of the following 3 criteria, POR applications fare less well than LOR applications: (1) POR status and ranking in the total application pool; (2) percentage of POR vs LOR applications in the top 20th percentile; and (3) funding rates of POR applications. Furthermore, the fate of a POR application depended on which study section reviewed the application. Those applications that were reviewed in study sections that primarily reviewed POR applications fared equivalently to LOR applications; in contrast, POR applications reviewed in study sections that primarily reviewed LOR applications encountered a less favorable fate.
These objective data provide strong support to the clinical research community's concern that investigator-initiated POR applications are not reviewed equitably at the NIH. By restructuring the review process, fairness is likely to be restored. Without restructuring, the POR component of the medical research community may be critically damaged.
Remarkable advances have been made recently in our understanding of the molecular and genetic bases of disease. The potential therapeutic opportunities offered by these scientific findings, combined with the expanding needs of an aging population, have led to broad-based congressional support for increases in the National Institutes of Health budget. These developments have put into sharp relief the question of how to allocate growing budgetary resources among the various categories of medical research. In addition to the need to support basic-science research, investigators and policy analysts alike have recently emphasized the need to invest in translational research and clinical evaluative . . .
When I learned in 1976 that I had been chosen as the seventh member of the the American Society for Clinical Oncology to deliver the prestigious Karnofsky Lecture, I was not only honored, but inspired. I felt that it would be my responsibility to discuss a topic that was of great importance and might have an impact on the future of clinical cancer research. The organizing committee for this Supplement recommended that the transcript of that talk be reproduced in conjunction with this publication to contrast my 1976 views with the views expressed at the time of the Festschrift Symposium in 1997. Moreover rite committee has offered me the opportunity to augment this publication with these editorial comments. In 1976, the reaction to my Karnofsky lecture was conservatively characterized as "highly controversial." There was a nucleus of innovative scientists,oho reacted positively to the talk, finding that it was consistent with many of their own experiences. A minority of fellows who reacted positively to the lecture carried some of "Freireich's Laws" into their careers. However the dominant reaction was extremely negative. In fact, it could be characterized as "hostile." The American Society for Clinical Oncology did nor yet have an official journal; the Journal of Clinical Oncology began its first publication in 1983. Because of this and the controversial nature of the lecture, it was never formally published. I would like to comment on the seven topics that I discussed in the 1976 Karnofsky lecture, which are subsequently reviewed in this Festschrift issue. The first topic was Regulation. There is no doubt that the problems I identified 20 years ago have led to a continuing escalation in the time from conception to marketing of a new chemical entity and to a progressive escalation of the cost. Both of these continue to be significant impediments to clinical research and to the development of innovative treatment. The positive change in attitude that has occurred oiler the last 20 years is the appreciation of benefit:risk ratios. I think that largely as the result of the politically active AIDS community, the regulations have been modified so that risk prevention is balanced against the seriousness of the the disease and the potential for benefit. Thus, the direction over the last 20 years has been unfavorable, but the predictions Sor the next millenium indicate a significant continuing improvement in the potential for reducing the impact of regulation of clinical cancer research. Clearly, for rite patient with cancer who has not only a life threatening disease but a limited prognosis, the requirements for preclinical testing can be substantially reduced. The need for continuing regulatory reform is emphasized both in the 1976 lecture and in my continuing efforts made in the academic medical community. The Health Care Delivery crisis has now evolved into a major threat to clinical cancer research. The emphasis on delivery of the best available health care in contrast to the investment necessary to develop the knowledge to improve both the quality and the cost of that cave has now led to the "managed care crisis." Clearly, there is a need for greater support for the clinical research that is so crucial to improving cancer control. As for Priorities for Investigation, the last 20 years have seen a tremendous growth and emphasis on "quality of life." We now have a significant euthanasia community who advocates a hospice type of terminal care for patients with hopelessly untreatable cancers. In contrast, a clinical research environment adds an important ingredient to the patient's quality of life, that is "hope" to replace hopelessness. Certainly, the last 20 years have seen a major improvement in both the curability and the quality of life for many patients. This has been a result of clinical research activities, and many patients with hopeless diagnoses have benefitted. Phase I and Phase II studies are crucial to developing new knowledge, and for each patient participating, they offer the hope that the treatment will benefit them. The section on Statistical Tyranny was, of course, amateurish, bur important at the time. Over the last 20 years, statistical theory has become infinitely more sophisticated. The introduction of stopping roles, techniques for interim analysis, Bayesian statistics, and so forth has greatly improved the quantitative techniques for the conduct of clinical research. Many statisticians felt that this lecture was a critique of statistical input into clinical research. Quite the contrary. The intent was to point out that clinicians who have only a superficial understanding of probability theory and statistical concepts should be cautious in the use of statistics for guiding their judgement of the effectiveness of treatment. The best strategy, and one I have adopted throughout my career is to rely on the expertise of an outstanding biostatistician. I have been fortunate to be able to consult with Dr. Ed Gehan and many other statisticians. The Academic Requirement question is one that has grown in importance in the last 20 years. The physician-scientist has been progressively excluded from the RO1 pool, and as I have emphasized iii my Festschrift paper (1), it is important for us to recognize the achievements of clinical scientists by different criteria than those that have been used for laboratory-based research. The False Positive-False Negative statement emphasizes the necessity for rite clinical investigator to have an optimistic view of the outcome of clinical trials and to focus his attention on discovering newer approaches rather than attempting to disprove claims inane by other investigators. The final subject of Ethics has a timelessness. The clinical investigator as a physician, has always had the responsibility of putting putting his patients' interests ahead of the interests of any other socioeconomic or political forces. As I reread my 1976 lecture, I find myself proud of having had the courage to expose my opinions, prejudices, and ignorance to the academic medical community. After the subsequent 20 years of full-time clinical research in cancer I Sind that I personally feel that Freireich's Seven Laws are a useful guide for my continuing research, and I believe that many other clinical scientists have sound them to be useful formulations of concepts that they hold dear. Hopefully, publication of the 1976 Karnofsky Award Lecture will have a positive influence on clinical investigators as we move into the next millenium .
It was a singular honor for me to give the second annual James A. Shannon Lecture at the National Institutes of Health last October. Indeed, I would not have been there at all without Shannon. That is not because I knew him personally, but rather because of the NIH that he — more than anyone else — created between 1949 and 1968. Shannon’s intelligence, vision, decisiveness, single-mindedness, and political acumen, first as Associate Director for Research of the National Heart Institute and then as Director of NIH, produced a powerful magnet that attracted me to Bethesda in 1959. Forty years later, I had the opportunity to reflect on why preparing one’s self for a career in research, as epitomized by coming to NIH, was so clearly the thing for recent medical school graduates to do then and, just as clearly and paradoxically, is not the thing to do today. What follows are my reflections I offered in the Shannon lecture.
Although formerly a prime intellectual focus of medical practice, research, and education, the pathophysiology of organs and organ systems has become increasingly deemphasized. The field of clinical investigation is thereby left without a sturdy bridge to connect epidemiologic studies of patients with cellular and molecular studies. The decline of pathophysiology has led to major defects in diagnostic reasoning and clinico-pathophysiologic correlations, to isolated accomplishments in molecular research, and to the neglect of many prominent scientific questions that can be asked and answered only at the level of organs and organ systems. An important intellectual source of the problem is the ideologic belief that scientific importance is inversely proportional to the size of the investigated entities. With this belief, the title of "basic" is excluded from fundamental scientific questions in any research that does not occur at the level of cells and molecules. Although recent changes in National Institutes of Health policy may augment the decreasing number of physician-investigators, the more serious intellectual problems of constrained scientific creativity will continue until the current ideology is revised.
Remarkable advances in modern biology have enhanced our understanding of disease, permitting us to define-and potentially to treat-illness at the cellular and molecular level. The challenge we now face as physicians and physician-scientists is ensuring that these advances find expression in clinical practice. Thus far, the distance from the bench to the bedside has been surprisingly difficult to span, reflecting the need to develop broader, more integrative approaches to understanding how component molecules and physiologic systems function in the context of the whole person. Although there appears to be a consensus about the need to pursue such integrative, patient-oriented research, a mechanism for training future investigators in this discipline is less well established. In this essay, we present and develop the rationale for a set of underlying principles for patient-oriented research that can be used to guide appropriate training in this field. We also describe briefly a recently established prototype program-the Harvard initiative in Patient-Associated Science: Training, Education, Understanding, and Research (PASTEUR)-that we hope will help cultivate patient-oriented investigators and catalyze the evolution of patient-oriented research into a fully realized academic discipline.
he presentation of coronary atherosclerosis can be grad-ual, because of progressive flow-limiting stenosis andexertional angina, or dramatic, with plaque rupture andthrombosis causing unstable angina, myocardial infarction, orsudden death. The importance of arterial remodeling, orpersistent change in vessel size, has recently become apparentin both situations. Arterial remodeling, not plaque size, hasbeen identified as the primary determinant of lumen size inthe presence of stable lesions. Similarly, luminal stenosis intransplant vasculopathy and with restenosis after angioplastyoccur mainly because of inward remodeling rather thanplaque growth. However, recent evidence also suggests thatadequate outward remodeling may be associated with anincreased risk of plaque rupture, the underlying cause of acutecoronary syndromes and sudden cardiac death.The term “arterial remodeling” has previously been used todescribe any change in vessel wall structure. More recently,however, it has been used specifically to refer to a change invessel size (or cross-sectional area within the external elasticlamina), and it is on this entity that this review is focused.Inward remodeling denotes a reduction in vessel size. Out-ward remodeling denotes an increase in vessel size. Variousother terms are used in the literature (the Table). Whenoutward remodeling is present but insufficient to preventluminal stenosis, it is referred to as inadequate outwardremodeling.
As we race toward the as yet unimagined scientific and medical triumphs of the 21st century, no one is more hopeful about the journey than I am. Nevertheless, moving ahead with cutting-edge research must not mean leaving behind well-established international standards for protecting human subjects in clinical trials. None of these principles is more important than the protection of research subjects by informed consent based on full disclosure of potential risks and benefits. I did not expect, or want, to complete my tenure as secretary of health and human services by raising questions about the safety of patients in clinical . . .
The scholarship of integration is concerned with making connections across scientific disciplines, placing the work of individual investigators and their specialty fields into a larger context, and educating nonspecialists. The authors focus their comments on the biomedical sciences, but observe that closer integration of the biomedical and behavioral sciences will be particularly crucial to advance understanding of the human brain. They observe that as biomedical sciences become more technologically sophisticated, progress is increasingly dependent on sciences such as physics, chemistry, engineering, and related fields. However, the scholarship of integration has been slower than other forms of scholarship to gain acceptance as an integral activity of the professoriate. The isolation of disciplines from one another, particularly at large universities, and the perception of interdisciplinary work as risky and professionally unrewarding are among the forces that may discourage integrative scholarship. In addition, a troubling disconnect exists between the scientific community and the larger public in the understanding of science. Leaders in academic medicine and science must develop strategies to move interdisciplinary work from the margins into the mainstream of academia. Solutions that have been proposed include creating new research entities and funding mechanisms dedicated to interdisciplinary work; reinvigorating the integrative role of the physician-scientist; and training specialists in translational research. The scientific community must also work to develop more effective means of communicating the importance of its work to the public.
Pig-to-primate organ survival has been extended from a few minutes to weeks and occasionally months, following the development of transgenic pigs that express human complement-regulatory proteins, efficient antibody removal technologies and immunosuppressive strategies. The current limitation to the clinical application of this technology is acute vascular rejection, and an understanding of the mechanisms of this process and the development of modalities to overcome it are key to making significant progress at solving the critical shortage of organs for transplantation. Approaches that address this issue are underway in a number of laboratories.
The finding that unregulated, continuous delivery of vascular endothelial growth factor to the myocardium causes the formation of hemangiomas and death in mice indicates that more research is required on this potent molecule before clinical trials can proceed.
Conventional concepts of the pathogenesis of acute coronary syndromes are changing. High-risk lesions are not necessarily the angiographically "tight" stenoses. Rather, unstable vulnerable lesions have large lipid cores and thin fibrous caps. Plaque instability relates closely to the development of inflammation within the intima. Acute coronary syndromes usually result from rupture of a vulnerable atherosclerotic plaque mechanistically linked to the inflammatory process. Stabilization of lesions, rather than percutaneous or surgical procedures, provides a new therapeutic target. Lipid lowering may stabilize lesions by mitigating the inflammatory response.
Organ shortage for liver transplantation continues to be a major problem. Non heart beating donors (NHBD) are gaining increasing importance as a potential source of transplantable organs for clinical use, mainly in kidney transplantation. Up to now, the experience in liver transplantation with this type of donors has been limited and has only been considered in donors in whom cardiac arrest (CA) has occurred at a known given time. This is due to the high risk of primary non-function and late complications related to intrahepatic biliary lesions when warm ischemia time (WIT) is not controlled. The method of retrieval of these organs should offer the possibility to stop liver injury, revert histologic lesions appeared after WIT, and to assess the quality of the potential donor liver. Based on the experience of kidney transplantation, total body cooling achieved by extracorporal cardiopulmonary bypass seems to be the best method. Moreover it allows the inclusion of a time for tissue oxygenation at 37 degrees C (Normothermic Recirculation, NR) prior to body cooling which has been shown to improve graft viability, and also allows a time to measure organ quality before transplantation. In our experience, we demonstrated that liver transplantation from NHBD is feasible; NR has beneficial effect on liver viability improving endothelial cell damage, hepatocyte energy charge and histological changes at 5 days. We also showed that time of cardiac arrest is determinant of graft viability; even if hepatocellular function is preserved after 40 minutes of CA using NR, irreversible intrahepatic biliary lesions are always present and burden long-term survival. Moreover, bypass pump and blood flows are directly related to WIT and the achievement of better pump flows may predict survival during NR. In animals with 40 minutes of CA, we also reported the possibility to manipulate the potential graft during NR with L-Arginine, Glycine and S-Adenosyl-Methyonine, which minimize endothelial and hepatocellular damage as well as lesions at 5 days. Further research needs to be done in order to confirm our experimental data.
Antivascular therapy may be considered as one of the most promising approaches in the treatment of cancer. Antivascular treatment may be divided in antiangiogenesis and vascular targeting. Antiangiogenic therapy prevents neovascularization by inhibiting proliferation, migration, and/or differentiation of endothelial cells. Vascular targeting is directed at the existing tumor vasculature. Several inhibitors of angiogenesis are currently being tested in clinical cancer trials. The challenge for the next decade is to incorporate antivascular approaches into conventional treatment strategies. This review will summarize the conceptual basis of antivascular therapy and discuss the potential role of these agents in the adjuvant, neoadjuvant, and perioperative treatment of cancer.
In this article Dr. Harris and attorney Alcorn propose the establishment of a governmentally regulated, posthumous organ market, with economic incentives for the donors, in order to increase the supply of transplantable organs. The authors review transplant technology, provide a short history of donation and sale of organs, tissues, and cells, discuss the various legislative approaches that have been made to increase the supply of organs, and analyze the problems with the open market approach. They conclude with a proposal for a regulated posthumous organ market.
In this review, we have suggested that chronic vascular rejection, defined as alloimmune-mediated graft vascular stenosis, is the primary cause of late cardiac and hepatic graft failure. It may also commonly contribute to late renal and pulmonary allograft loss. In contrast, parenchymal changes in these failing grafts likely reflect ischemia rather than chronic parenchymal cell rejection. Vascular stenosis results from a combination of intimal hyperplasia and constrictive remodeling. In chronic vascular rejection, as in other chronic vascular diseases (e.g., atherosclerosis), constrictive remodeling caused by adventitial cicatrix formation may be the more important contributor to lumen loss. Functional vascular dysregulation due to endothelial injury may exacerbate the degree of stenosis by promoting vasoconstriction. The precise immunological mechanisms that cause chronic vascular rejection are unknown. Chronic DTH, mediated by host CD4+ T cells activated by graft alloantigens that are presented directly by graft endothelial and dendritic cells or indirectly by host dendritic cells, is a likely candidate. Evidence that IFN-γ, the prototypic cytokine of DTH, is necessary and sufficient to cause vascular remodeling in experimental transplantation supports this concept. (Animal models have limitations in recreating the human disease, although they do provide insights into possible mechanisms.) Alternatively, low-level, smoldering acute vascular rejection mediated by CD8+ CTL or alloantibodies could contribute to graft vascular disease. Nonimmunological factors, such as ischemia/reperfusion, hypertension, hyperlipidemia, and infection, all of which contribute to atherosclerotic vascular disease, all increase the incidence of chronic vascular rejection. These factors may act by enhancing the total burden of injury in the blood vessels or by activating the innate immune system, which favors the development of DTH. Human studies have not as yet resolved these issues. We currently lack effective preventive or therapeutic strategies for chronic vascular rejection. Current immunosuppressive regimens, which effectively prevent or abrogate acute rejection episodes, may target the wrong mechanisms; newer agents, such as rapamycin, may be more effective. Control of hypertension and restoration of normal lipid profiles, e.g., with HMG-CoA reductase inhibitors, may also be of benefit. In the future, as the pathogenesis is better understood, somatic gene therapy may provide a new avenue for therapy.
A high cholesterol diet is known to promote the formation of atherosclerotic plaques in arteries, leading to coronary heart
disease. However, there are four monogenic diseases in which plasma cholesterol increases independently of diet due to defects
in liver LDL receptors, which fail to clear cholesterol-carrying LDLs from plasma. In a lively and informative Perspective,
Brown and Goldstein
discuss the newest member of the cholesterol disease quartet, autosomal recessive hypercholesterolemia (ARH), and speculate
how mutations in the ARH protein could lead to defective functioning of liver LDL receptors.
Inflammation plays a pivotal role in both the development of atherosclerosis and the acute activation of the vascular wall with consequent local thrombosis and vasoconstriction (with or without plaque fissure). In many patients with unstable angina and acute myocardial infarction, systemic signs of inflammation are detectable. The use of systemic inflammatory markers, such as C-reactive protein as marker of disease activity and short- and long-term prognosis, seems to be of clinical value. Therefore, acute inflammatory reaction, detectable systematically, appears to be an independent determinant of prognosis in some patients with acute ischemic syndromes, but is not detectable in all. Understanding the causes of inflammation and the additional elusive components that result in the progression to aggressive acute coronary syndromes, is the future goal of cardiology.
A (2000) A gap between lab results and lives saved. The Boston Globe
- D A Shaywitz
- D Ausiello
Shaywitz, D. A., and Ausiello, D. A (2000) A gap between lab results and lives saved. The Boston Globe, p. D2
Pathophysiology of ischaemia-reperfusion injury
- D. L. Carden
- D. N. Granger
A gap between lab results and lives saved
- Shaywitz D. A.