Barriers and strategies for the clinical translation of advanced orthopaedic tissue engineering protocols.

PubMed

Madry, H; Alini, M; Stoddart, M J; Evans, C; Miclau, T; Steiner, S

2014-05-06

Research in orthopaedic tissue engineering has intensified over the last decade and new protocols continue to emerge. The clinical translation of these new applications, however, remains associated with a number of obstacles. This report highlights the major issues that impede the clinical translation of advanced tissue engineering concepts, discusses strategies to overcome these barriers, and examines the need to increase incentives for translational strategies. The statements are based on presentations and discussions held at the AO Foundation-sponsored symposium "Where Science meets Clinics 2013" held at the Congress Center in Davos, Switzerland, in September, 2013. The event organisers convened a diverse group of over one hundred stakeholders involved in clinical translation of orthopaedic tissue engineering, including scientists, clinicians, healthcare industry professionals and regulatory agency representatives. A major point that emerged from the discussions was that there continues to be a critical need for early trans-disciplinary communication and collaboration in the development and execution of research approaches. Equally importantly was the need to address the shortage of sustained funding programs for multidisciplinary teams conducting translational research. Such detailed discussions between experts contribute towards the development of a roadmap to more successfully advance the clinical translation of novel tissue engineering concepts and ultimately improve patient care in orthopaedic and trauma surgery.

Reorganizing the General Clinical Research Center to improve the clinical and translational research enterprise.

PubMed

Allen, David; Ripley, Elizabeth; Coe, Antoinette; Clore, John

2013-12-01

In 2010, Virginia Commonwealth University (VCU) was granted a Clinical and Translational Science Award which prompted reorganization and expansion of their clinical research infrastructure. A case study approach is used to describe the implementation of a business and cost recovery model for clinical and translational research and the transformation of VCU's General Clinical Research Center and Clinical Trials Office to a combined Clinical Research Services entity. We outline the use of a Plan, Do, Study, Act cycle that facilitated a thoughtful transition process, which included the identification of required changes and cost recovery processes for implementation. Through this process, the VCU Center for Clinical and Translational Research improved efficiency, increased revenue recovered, reduced costs, and brought a high level of fiscal responsibility through financial reporting.

Non-clinical studies required for new drug development - Part I: early in silico and in vitro studies, new target discovery and validation, proof of principles and robustness of animal studies.

PubMed

Andrade, E L; Bento, A F; Cavalli, J; Oliveira, S K; Freitas, C S; Marcon, R; Schwanke, R C; Siqueira, J M; Calixto, J B

2016-10-24

This review presents a historical overview of drug discovery and the non-clinical stages of the drug development process, from initial target identification and validation, through in silico assays and high throughput screening (HTS), identification of leader molecules and their optimization, the selection of a candidate substance for clinical development, and the use of animal models during the early studies of proof-of-concept (or principle). This report also discusses the relevance of validated and predictive animal models selection, as well as the correct use of animal tests concerning the experimental design, execution and interpretation, which affect the reproducibility, quality and reliability of non-clinical studies necessary to translate to and support clinical studies. Collectively, improving these aspects will certainly contribute to the robustness of both scientific publications and the translation of new substances to clinical development.

Emergency Medicine Resources Within the Clinical Translational Science Institutes: A Cross-sectional Study.

PubMed

Meurer, William J; Quinn, James; Lindsell, Christopher; Schneider, Sandra; Newgard, Craig D

2016-06-01

The Clinical and Translational Science Award (CTSA) program aims to strengthen and support translational research by accelerating the process of translating laboratory discoveries into treatments for patients, training a new generation of clinical and translational researchers, and engaging communities in clinical research efforts. Yet, little is known about how emergency care researchers have interacted with and utilized the resources of academic institutions with CTSAs. The purpose of this survey was to describe how emergency care researchers use local CTSA resources, to ascertain what proportion of CTSA consortium members have active emergency care research (ECR) programs, and to solicit participation in a national CTSA-associated emergency care translational research network. This study was a survey of all emergency departments affiliated with a CTSA. Of the 65 CTSA consortium members, three had no ECR program and we obtained responses from 46 of the remaining 62 (74% response rate). The interactions with and resources used by emergency care researchers varied widely. Methodology and biostatistics support was most frequently accessed (77%), followed closely by education and training programs (60%). Several ECR programs (76%) had submitted for funding through CTSAs, with 71% receiving awards. Most CTSA consortium members had an active ECR infrastructure: 21 (46%) had 24/7 availability to recruit and screen for research, and 21 (46%) had less than 24/7 research recruitment. A number of emergency care research programs participated in National Institutes of Health research networks with the Neurological Emergencies Treatment Trials network most highly represented with 23 (59%) sites. Most ECR programs (96%) were interested in participating in a CTSA-based emergency care translational research network. Despite little initial involvement in development of the CTSA program, there has been moderate interaction between CTSAs and emergency care. There is considerable

Using Skype to support remote clinical supervision for health professionals delivering a sustained maternal early childhood programme: a phenomenographical study.

PubMed

Bruce, Tracey; Byrne, Fiona; Kemp, Lynn

2018-02-01

Skype technology was implemented by the Australian Maternal Early Childhood Sustained Home-visiting (MECSH) Support Service as a tool for the remote provision of clinical supervision for clinicians working in the MECSH program in Seoul, South Korea. To gain a better understanding of the processes underpinning sustainable delivery of remote clinical supervision using digital technologies. A phenomenographical study. Recorded notes and reflections on each supervision session, noting exemplars and characteristics of the experience were read and re-read to derive the characterizations of the experience. The experience has provided learnings in three domains: (1) the processes in using Skype; (2) supervisory processes; and (3) language translation, including managing clarity of, and time for translation. Skype has potential for use in remote provision of clinical supervision, including where translation is required. Further research evaluating the benefit of telesupervision from supervisor and supervisee perspectives is necessary to determine if it is a sustainable process.

Accelerating Translational Research by Clinically Driven Development of an Informatics Platform–A Case Study

PubMed Central

Abugessaisa, Imad; Saevarsdottir, Saedis; Tsipras, Giorgos; Lindblad, Staffan; Sandin, Charlotta; Nikamo, Pernilla; Ståhle, Mona; Malmström, Vivianne; Klareskog, Lars; Tegnér, Jesper

2014-01-01

Translational medicine is becoming increasingly dependent upon data generated from health care, clinical research, and molecular investigations. This increasing rate of production and diversity in data has brought about several challenges, including the need to integrate fragmented databases, enable secondary use of patient clinical data from health care in clinical research, and to create information systems that clinicians and biomedical researchers can readily use. Our case study effectively integrates requirements from the clinical and biomedical researcher perspectives in a translational medicine setting. Our three principal achievements are (a) a design of a user-friendly web-based system for management and integration of clinical and molecular databases, while adhering to proper de-identification and security measures; (b) providing a real-world test of the system functionalities using clinical cohorts; and (c) system integration with a clinical decision support system to demonstrate system interoperability. We engaged two active clinical cohorts, 747 psoriasis patients and 2001 rheumatoid arthritis patients, to demonstrate efficient query possibilities across the data sources, enable cohort stratification, extract variation in antibody patterns, study biomarker predictors of treatment response in RA patients, and to explore metabolic profiles of psoriasis patients. Finally, we demonstrated system interoperability by enabling integration with an established clinical decision support system in health care. To assure the usefulness and usability of the system, we followed two approaches. First, we created a graphical user interface supporting all user interactions. Secondly we carried out a system performance evaluation study where we measured the average response time in seconds for active users, http errors, and kilobits per second received and sent. The maximum response time was found to be 0.12 seconds; no server or client errors of any kind were detected

Accelerating translational research by clinically driven development of an informatics platform--a case study.

PubMed

Abugessaisa, Imad; Saevarsdottir, Saedis; Tsipras, Giorgos; Lindblad, Staffan; Sandin, Charlotta; Nikamo, Pernilla; Ståhle, Mona; Malmström, Vivianne; Klareskog, Lars; Tegnér, Jesper

2014-01-01

Translational medicine is becoming increasingly dependent upon data generated from health care, clinical research, and molecular investigations. This increasing rate of production and diversity in data has brought about several challenges, including the need to integrate fragmented databases, enable secondary use of patient clinical data from health care in clinical research, and to create information systems that clinicians and biomedical researchers can readily use. Our case study effectively integrates requirements from the clinical and biomedical researcher perspectives in a translational medicine setting. Our three principal achievements are (a) a design of a user-friendly web-based system for management and integration of clinical and molecular databases, while adhering to proper de-identification and security measures; (b) providing a real-world test of the system functionalities using clinical cohorts; and (c) system integration with a clinical decision support system to demonstrate system interoperability. We engaged two active clinical cohorts, 747 psoriasis patients and 2001 rheumatoid arthritis patients, to demonstrate efficient query possibilities across the data sources, enable cohort stratification, extract variation in antibody patterns, study biomarker predictors of treatment response in RA patients, and to explore metabolic profiles of psoriasis patients. Finally, we demonstrated system interoperability by enabling integration with an established clinical decision support system in health care. To assure the usefulness and usability of the system, we followed two approaches. First, we created a graphical user interface supporting all user interactions. Secondly we carried out a system performance evaluation study where we measured the average response time in seconds for active users, http errors, and kilobits per second received and sent. The maximum response time was found to be 0.12 seconds; no server or client errors of any kind were detected

Closing the gap between knowledge and clinical application: challenges for genomic translation.

PubMed

Burke, Wylie; Korngiebel, Diane M

2015-01-01

Despite early predictions and rapid progress in research, the introduction of personal genomics into clinical practice has been slow. Several factors contribute to this translational gap between knowledge and clinical application. The evidence available to support genetic test use is often limited, and implementation of new testing programs can be challenging. In addition, the heterogeneity of genomic risk information points to the need for strategies to select and deliver the information most appropriate for particular clinical needs. Accomplishing these tasks also requires recognition that some expectations for personal genomics are unrealistic, notably expectations concerning the clinical utility of genomic risk assessment for common complex diseases. Efforts are needed to improve the body of evidence addressing clinical outcomes for genomics, apply implementation science to personal genomics, and develop realistic goals for genomic risk assessment. In addition, translational research should emphasize the broader benefits of genomic knowledge, including applications of genomic research that provide clinical benefit outside the context of personal genomic risk.

Translational neural engineering: multiple perspectives on bringing benchtop research into the clinical domain

PubMed Central

Rousche, Patrick; Schneeweis, David M; Perreault, Eric J; Jensen, Winnie

2009-01-01

A half-day forum to address a wide range of issues related to translational neural engineering was conducted at the annual meeting of the Biomedical Engineering Society. Successful practitioners of translational neural engineering from academics, clinical medicine and industry were invited to share a diversity of perspectives and experiences on the translational process. The forum was targeted towards traditional academic researchers who may be interested in the expanded funding opportunities available for translational research that emphasizes product commercialization and clinical implementation. The seminar was funded by the NIH with support from the Rehabilitation Institute of Chicago. We report here a summary of the speaker viewpoints with particular focus on extracting successful strategies for engaging in or conducting translational neural engineering research. Daryl Kipke, PhD, (Department of Biomedical Engineering at the University of Michigan) and Molly Shoichet, PhD, (Department of Chemical Engineering at the University of Toronto) gave details of their extensive experience with product commercialization while holding primary appointments in academic departments. They both encouraged strong clinical input at very early stages of research. Neurosurgeon Fady Charbel, MD, (Department of Neurosurgery at the University of Illinois at Chicago) discussed his role in product commercialization as a clinician. Todd Kuiken, MD, PhD, (Director of the Neural Engineering for Artificial Limbs at the Rehabilitation Institute of Chicago, affiliated with Northwestern University) also a clinician, described a model of translational engineering that emphasized the development of clinically relevant technology, without a strong commercialization imperative. The clinicians emphasized the importance of communicating effectively with engineers. Representing commercial neural engineering was Doug Sheffield, PhD, (Director of New Technology at Vertis Neuroscience, Inc.) who

Translational neural engineering: multiple perspectives on bringing benchtop research into the clinical domain.

PubMed

Rousche, Patrick; Schneeweis, David M; Perreault, Eric J; Jensen, Winnie

2008-03-01

A half-day forum to address a wide range of issues related to translational neural engineering was conducted at the annual meeting of the Biomedical Engineering Society. Successful practitioners of translational neural engineering from academics, clinical medicine and industry were invited to share a diversity of perspectives and experiences on the translational process. The forum was targeted towards traditional academic researchers who may be interested in the expanded funding opportunities available for translational research that emphasizes product commercialization and clinical implementation. The seminar was funded by the NIH with support from the Rehabilitation Institute of Chicago. We report here a summary of the speaker viewpoints with particular focus on extracting successful strategies for engaging in or conducting translational neural engineering research. Daryl Kipke, PhD, (Department of Biomedical Engineering at the University of Michigan) and Molly Shoichet, PhD, (Department of Chemical Engineering at the University of Toronto) gave details of their extensive experience with product commercialization while holding primary appointments in academic departments. They both encouraged strong clinical input at very early stages of research. Neurosurgeon Fady Charbel, MD, (Department of Neurosurgery at the University of Illinois at Chicago) discussed his role in product commercialization as a clinician. Todd Kuiken, MD, PhD, (Director of the Neural Engineering for Artificial Limbs at the Rehabilitation Institute of Chicago, affiliated with Northwestern University) also a clinician, described a model of translational engineering that emphasized the development of clinically relevant technology, without a strong commercialization imperative. The clinicians emphasized the importance of communicating effectively with engineers. Representing commercial neural engineering was Doug Sheffield, PhD, (Director of New Technology at Vertis Neuroscience, Inc.) who

Vision, Identity, and Career in the Clinical and Translational Sciences: Building upon the Formative Years

PubMed Central

Martinez, Dominic F.; Buchwald, Dedra S.; Rubio, Doris M.; Moss, Marc

2015-01-01

Abstract This paper is the second in a five‐part series on the clinical and translational science educational pipeline. It focuses on the role that Clinical and Translational Science Award (CTSA) programs can play in supporting science, technology, engineering, and math (STEM) education in primary and secondary schools, as well as in facilitating these interests during transition to undergraduate training. Special emphasis should be placed on helping to form and sustain an identity as a scientist, and on instilling the persistence necessary to overcome numerous barriers to its actualization. CTSAs can contribute to cementing this sense of self by facilitating peer support, mentorship, and family involvement that will reinforce early educational decisions leading to clinical and translational science research careers. Meanwhile, the interests, skills, and motivation induced by participation in STEM programs must be sustained in transition to the next level in the educational pipeline, typically undergraduate study. Examples of CTSA collaborations with local schools, businesses, interest groups, and communities at large illustrate the emerging possibilities and promising directions with respect to each of these challenges. PMID:26271774

Vision, Identity, and Career in the Clinical and Translational Sciences: Building upon the Formative Years.

PubMed

Manson, Spero M; Martinez, Dominic F; Buchwald, Dedra S; Rubio, Doris M; Moss, Marc

2015-10-01

This paper is the second in a five-part series on the clinical and translational science educational pipeline. It focuses on the role that Clinical and Translational Science Award (CTSA) programs can play in supporting science, technology, engineering, and math (STEM) education in primary and secondary schools, as well as in facilitating these interests during transition to undergraduate training. Special emphasis should be placed on helping to form and sustain an identity as a scientist, and on instilling the persistence necessary to overcome numerous barriers to its actualization. CTSAs can contribute to cementing this sense of self by facilitating peer support, mentorship, and family involvement that will reinforce early educational decisions leading to clinical and translational science research careers. Meanwhile, the interests, skills, and motivation induced by participation in STEM programs must be sustained in transition to the next level in the educational pipeline, typically undergraduate study. Examples of CTSA collaborations with local schools, businesses, interest groups, and communities at large illustrate the emerging possibilities and promising directions with respect to each of these challenges. © 2015 Wiley Periodicals, Inc.

Faithful interpreters? Translation theory and practice at the early Royal Society

PubMed Central

Henderson, Felicity

2013-01-01

The early Fellows of the Royal Society received letters, papers and printed books written in several European vernaculars. In many cases a translation was needed to make these texts accessible. Translators, though, had to negotiate the Society's corporate views on language and prose style, and also prevailing contemporary theories of literary translation set out by popular poets such as John Dryden and Abraham Cowley. This article examines the translation practices of early Fellows of the Royal Society, showing that translations formed part of a set of knowledge-making processes at meetings. It also discusses the statements about translation theory found in the prefaces to printed volumes produced by or for Royal Society Fellows, arguing that although translators were aware of the requirement for a faithful translation, in fact they often modified their source texts to make them more useful for an English audience.

Ischaemic conditioning: pitfalls on the path to clinical translation

PubMed Central

Przyklenk, Karin

2015-01-01

The development of novel adjuvant strategies capable of attenuating myocardial ischaemia-reperfusion injury and reducing infarct size remains a major, unmet clinical need. A wealth of preclinical evidence has established that ischaemic ‘conditioning’ is profoundly cardioprotective, and has positioned the phenomenon (in particular, the paradigms of postconditioning and remote conditioning) as the most promising and potent candidate for clinical translation identified to date. However, despite this preclinical consensus, current phase II trials have been plagued by heterogeneity, and the outcomes of recent meta-analyses have largely failed to confirm significant benefit. As a result, the path to clinical application has been perceived as ‘disappointing’ and ‘frustrating’. The goal of the current review is to discuss the pitfalls that may be stalling the successful clinical translation of ischaemic conditioning, with an emphasis on concerns regarding: (i) appropriate clinical study design and (ii) the choice of the ‘right’ preclinical models to facilitate clinical translation. PMID:25560903

A community translational research pilot grants program to facilitate community--academic partnerships: lessons from Colorado's clinical translational science awards.

PubMed

Main, Deborah S; Felzien, Maret C; Magid, David J; Calonge, B Ned; O'Brien, Ruth A; Kempe, Allison; Nearing, Kathryn

2012-01-01

National growth in translational research has increased the need for practical tools to improve how academic institutions engage communities in research. One used by the Colorado Clinical and Translational Sciences Institute (CCTSI) to target investments in community-based translational research on health disparities is a Community Engagement (CE) Pilot Grants program. Innovative in design, the program accepts proposals from either community or academic applicants, requires that at least half of requested grant funds go to the community partner, and offers two funding tracks: One to develop new community-academic partnerships (up to $10,000), the other to strengthen existing partnerships through community translational research projects (up to $30,000). We have seen early success in both traditional and capacity building metrics: the initial investment of $272,742 in our first cycle led to over $2.8 million dollars in additional grant funding, with grantees reporting strengthening capacity of their community- academic partnerships and the rigor and relevance of their research.

PERSPECTIVE: Translational neural engineering: multiple perspectives on bringing benchtop research into the clinical domain

NASA Astrophysics Data System (ADS)

Rousche, Patrick; Schneeweis, David M.; Perreault, Eric J.; Jensen, Winnie

2008-03-01

A half-day forum to address a wide range of issues related to translational neural engineering was conducted at the annual meeting of the Biomedical Engineering Society. Successful practitioners of translational neural engineering from academics, clinical medicine and industry were invited to share a diversity of perspectives and experiences on the translational process. The forum was targeted towards traditional academic researchers who may be interested in the expanded funding opportunities available for translational research that emphasizes product commercialization and clinical implementation. The seminar was funded by the NIH with support from the Rehabilitation Institute of Chicago. We report here a summary of the speaker viewpoints with particular focus on extracting successful strategies for engaging in or conducting translational neural engineering research. Daryl Kipke, PhD, (Department of Biomedical Engineering at the University of Michigan) and Molly Shoichet, PhD, (Department of Chemical Engineering at the University of Toronto) gave details of their extensive experience with product commercialization while holding primary appointments in academic departments. They both encouraged strong clinical input at very early stages of research. Neurosurgeon Fady Charbel, MD, (Department of Neurosurgery at the University of Illinois at Chicago) discussed his role in product commercialization as a clinician. Todd Kuiken, MD, PhD, (Director of the Neural Engineering for Artificial Limbs at the Rehabilitation Institute of Chicago, affiliated with Northwestern University) also a clinician, described a model of translational engineering that emphasized the development of clinically relevant technology, without a strong commercialization imperative. The clinicians emphasized the importance of communicating effectively with engineers. Representing commercial neural engineering was Doug Sheffield, PhD, (Director of New Technology at Vertis Neuroscience, Inc.) who

Emergency Medicine Resources within the Clinical Translational Science Institutes: A Cross-Sectional Study

PubMed Central

Meurer, William J.; Quinn, James; Lindsell, Christopher; Schneider, Sandra; Newgard, Craig D.

2016-01-01

Background The Clinical and Translational Science Award (CTSA) program aims to strengthen and support translational research by accelerating the process of translating laboratory discoveries into treatments for patients, training a new generation of clinical and translational researchers, and engaging communities in clinical research efforts. Yet, little is known about how emergency care researchers have interacted with and utilized the resources of academic institutions with CTSAs. Objective The purpose of this survey was to describe how emergency care researchers use local CTSA resources, to ascertain what proportion of CTSA consortium members have active emergency care research programs, and to solicit participation in a national CTSA-associated emergency care translational research network. Methods Survey of all emergency departments affiliated with a CTSA. Results Of the 65 CTSA consortium members, three had no emergency care research program and we obtained responses from 46 of the remaining 62 (74% response rate). The interactions with and resources used by emergency care researchers varied widely. Methodology and biostatistics support was most frequently accessed (77%), followed closely by education and training programs (60%). Several emergency care research programs (76%) had submitted for funding through CTSAs, with 71% receiving awards. Most CTSA consortium members had an active emergency care research infrastructure: 21 (46%) had 24/7 availability to recruit and screen for research, 21 (46%) had less than 24/7 research recruitment. A number of emergency care research programs participated in NIH research networks with the Neurological Emergencies Treatment Trials network most highly represented with 23 (59%) sites. Most emergency care research programs (96%) were interested in participating in a CTSA-based emergency care translational research network. Conclusions Despite little initial involvement in development of the CTSA program, there has been

Translating research and into everyday clinical practice: Lessons learned from a USA national dental practice-based research network

PubMed Central

Gordan, Valeria V.

2012-01-01

Clinical studies are of paramount importance for testing and translation of the research findings to the community. Despite the existence of clinical studies, a significant delay exists between the generation of new knowledge and its application into the medical/dental community and their patients. One example is the repair of defective dental restorations. About 75% of practitioners in general dental practices do not consider the repair of dental restorations as a viable alternative to the replacement of defective restorations. Engaging and partnering with health practitioners in the field on studies addressing everyday clinical research questions may offer a solution to speed up the translation of the research findings. Practice-based research (PBR) offers a unique opportunity for practitioners to be involved in the research process, formulating clinical research questions. Additionally, PBR generates evidence-based knowledge with a broader spectrum that can be more readily generalized to the public. With PBR, clinicians are involved in the entire research process from its inception to its dissemination. Early practitioner interaction in the research process may result in ideas being more readily incorporated into practice. This paper discusses PBR as a mean to speed up the translation of research findings to clinical practice. It also reviews repair versus replacement of defective restorations as one example of the delay in the application of research findings to clinical practice. PMID:22889478

The Translational Science Benefits Model: A New Framework for Assessing the Health and Societal Benefits of Clinical and Translational Sciences

PubMed Central

Sarli, Cathy C.; Suiter, Amy M.; Carothers, Bobbi J.; Combs, Todd B.; Allen, Jae L.; Beers, Courtney E.; Evanoff, Bradley A.

2017-01-01

Abstract We report the development of the Translational Science Benefits Model (TSBM), a framework designed to support institutional assessment of clinical and translational research outcomes to measure clinical and community health impacts beyond bibliometric measures. The TSBM includes 30 specific and potentially measurable indicators that reflect benefits that accrue from clinical and translational science research such as products, system characteristics, or activities. Development of the TSBM was based on literature review, a modified Delphi method, and in‐house expert panel feedback. Three case studies illustrate the feasibility and face validity of the TSBM for identification of clinical and community health impacts that result from translational science activities. Future plans for the TSBM include further pilot testing and a resource library that will be freely available for evaluators, translational scientists, and academic institutions who wish to implement the TSBM framework in their own evaluation efforts. PMID:28887873

Scaffold Translation: Barriers Between Concept and Clinic

PubMed Central

Murphy, William L.

2011-01-01

Translation of scaffold-based bone tissue engineering (BTE) therapies to clinical use remains, bluntly, a failure. This dearth of translated tissue engineering therapies (including scaffolds) remains despite 25 years of research, research funding totaling hundreds of millions of dollars, over 12,000 papers on BTE and over 2000 papers on BTE scaffolds alone in the past 10 years (PubMed search). Enabling scaffold translation requires first an understanding of the challenges, and second, addressing the complete range of these challenges. There are the obvious technical challenges of designing, manufacturing, and functionalizing scaffolds to fill the Form, Fixation, Function, and Formation needs of bone defect repair. However, these technical solutions should be targeted to specific clinical indications (e.g., mandibular defects, spine fusion, long bone defects, etc.). Further, technical solutions should also address business challenges, including the need to obtain regulatory approval, meet specific market needs, and obtain private investment to develop products, again for specific clinical indications. Finally, these business and technical challenges present a much different model than the typical research paradigm, presenting the field with philosophical challenges in terms of publishing and funding priorities that should be addressed as well. In this article, we review in detail the technical, business, and philosophical barriers of translating scaffolds from Concept to Clinic. We argue that envisioning and engineering scaffolds as modular systems with a sliding scale of complexity offers the best path to addressing these translational challenges. PMID:21902613

Scaffold translation: barriers between concept and clinic.

PubMed

Hollister, Scott J; Murphy, William L

2011-12-01

Translation of scaffold-based bone tissue engineering (BTE) therapies to clinical use remains, bluntly, a failure. This dearth of translated tissue engineering therapies (including scaffolds) remains despite 25 years of research, research funding totaling hundreds of millions of dollars, over 12,000 papers on BTE and over 2000 papers on BTE scaffolds alone in the past 10 years (PubMed search). Enabling scaffold translation requires first an understanding of the challenges, and second, addressing the complete range of these challenges. There are the obvious technical challenges of designing, manufacturing, and functionalizing scaffolds to fill the Form, Fixation, Function, and Formation needs of bone defect repair. However, these technical solutions should be targeted to specific clinical indications (e.g., mandibular defects, spine fusion, long bone defects, etc.). Further, technical solutions should also address business challenges, including the need to obtain regulatory approval, meet specific market needs, and obtain private investment to develop products, again for specific clinical indications. Finally, these business and technical challenges present a much different model than the typical research paradigm, presenting the field with philosophical challenges in terms of publishing and funding priorities that should be addressed as well. In this article, we review in detail the technical, business, and philosophical barriers of translating scaffolds from Concept to Clinic. We argue that envisioning and engineering scaffolds as modular systems with a sliding scale of complexity offers the best path to addressing these translational challenges. © Mary Ann Liebert, Inc.

Regenerative endodontics: barriers and strategies for clinical translation.

PubMed

Mao, Jeremy J; Kim, Sahng G; Zhou, Jian; Ye, Ling; Cho, Shoko; Suzuki, Takahiro; Fu, Susan Y; Yang, Rujing; Zhou, Xuedong

2012-07-01

Regenerative endodontics has encountered substantial challenges toward clinical translation. The adoption by the American Dental Association of evoked pulp bleeding in immature permanent teeth is an important step for regenerative endodontics. However, there is no regenerative therapy for most endodontic diseases. Simple recapitulation of cell therapy and tissue engineering strategies that are under development for other organ systems has not led to clinical translation in regeneration endodontics. Recent work using novel biomaterial scaffolds and growth factors that orchestrate the homing of host endogenous cells represents a departure from traditional cell transplantation approaches and may accelerate clinical translation. Copyright © 2012 Elsevier Inc. All rights reserved.

Whole kidney engineering for clinical translation.

PubMed

Kim, Ick-Hee; Ko, In Kap; Atala, Anthony; Yoo, James J

2015-04-01

Renal transplantation is currently the only definitive treatment for end-stage renal disease; however, this treatment is severely limited by the shortage of implantable kidneys. To address this shortcoming, development of an engineered, transplantable kidney has been proposed. Although current advances in engineering kidneys based on decellularization and recellularization techniques have offered great promises for the generation of functional kidney constructs, most studies have been conducted using rodent kidney constructs and short-term in-vivo evaluation. Toward clinical translations of this technique, several limitations need to be addressed. Human-sized renal scaffolds are desirable for clinical application, and the fabrication is currently feasible using native porcine and discarded human kidneys. Current progress in stem cell biology and cell culture methods have demonstrated feasibility of the use of embryonic stem cells, induced pluripotent stem cells, and primary renal cells as clinically relevant cell sources for the recellularization of renal scaffolds. Finally, approaches to long-term implantation of engineered kidneys are under investigation using antithrombogenic strategies such as functional reendothelialization of acellular kidney matrices. In the field of bioengineering, whole kidneys have taken a number of important initial steps toward clinical translations, but many challenges must be addressed to achieve a successful treatment for the patient with end-stage renal disease.

Resveratrol and cancer: Challenges for clinical translation

PubMed Central

Singh, Chandra K.; Ndiaye, Mary A.; Ahmad, Nihal

2014-01-01

Significant work has been done towards identifying the health-beneficial effects of the grape antioxidant resveratrol in a variety of bioassay- and disease- models, with much research being focused on its possible application to cancer management. Despite the large number of preclinical studies dealing with different aspects of the biological effects of resveratrol, it’s translation to clinics is far from reality due to a variety of challenges. In this review, we discuss the issues and questions associated with resveratrol becoming an effective in vivo anticancer drug, from basic metabolic issues to the problems faced by incomplete understanding of the mechanism(s) of action in the body. We also explore efforts taken by researchers, both public and private, to contend with some of these issues. By examining the published data and previous clinical trials, we have attempted to identify the problems and issues that hinder the clinical translation of resveratrol for cancer management. PMID:25446990

Mitochondrial Disease: Clinical Aspects, Molecular Mechanisms, Translational Science, and Clinical Frontiers

PubMed Central

Thornton, Ben; Cohen, Bruce; Copeland, William; Maria, Bernard L.

2015-01-01

Mitochondrial medicine provides a metabolic perspective on the pathology of conditions linked with inadequate oxidative phosphorylation. Dysfunction in the mitochondrial machinery can result in improper energy production, leading to cellular injury or even apoptosis. Clinical presentations are often subtle, so clinicians must have a high index of suspicion to make early diagnoses. Symptoms could include muscle weakness and pain, seizures, loss of motor control, decreased visual and auditory functions, metabolic acidosis, acute developmental regression, and immune system dysfunction. The 2013 Neurobiology of Disease in Children Symposium, held in conjunction with the 42nd Annual Meeting of the Child Neurology Society, aimed to (1) describe accepted clinical phenotypes of mitochondrial disease produced from various mitochondrial mutations, (2) discuss contemporary understanding of molecular mechanisms that contribute to disease pathology, (3) highlight the systemic effects produced by dysfunction within the mitochondrial machinery, and (4) introduce current strategies that are being translated from bench to bedside as potential therapeutics. PMID:24916430

Big data from electronic health records for early and late translational cardiovascular research: challenges and potential.

PubMed

Hemingway, Harry; Asselbergs, Folkert W; Danesh, John; Dobson, Richard; Maniadakis, Nikolaos; Maggioni, Aldo; van Thiel, Ghislaine J M; Cronin, Maureen; Brobert, Gunnar; Vardas, Panos; Anker, Stefan D; Grobbee, Diederick E; Denaxas, Spiros

2018-04-21

Cohorts of millions of people's health records, whole genome sequencing, imaging, sensor, societal and publicly available data present a rapidly expanding digital trace of health. We aimed to critically review, for the first time, the challenges and potential of big data across early and late stages of translational cardiovascular disease research. We sought exemplars based on literature reviews and expertise across the BigData@Heart Consortium. We identified formidable challenges including: data quality, knowing what data exist, the legal and ethical framework for their use, data sharing, building and maintaining public trust, developing standards for defining disease, developing tools for scalable, replicable science and equipping the clinical and scientific work force with new inter-disciplinary skills. Opportunities claimed for big health record data include: richer profiles of health and disease from birth to death and from the molecular to the societal scale; accelerated understanding of disease causation and progression, discovery of new mechanisms and treatment-relevant disease sub-phenotypes, understanding health and diseases in whole populations and whole health systems and returning actionable feedback loops to improve (and potentially disrupt) existing models of research and care, with greater efficiency. In early translational research we identified exemplars including: discovery of fundamental biological processes e.g. linking exome sequences to lifelong electronic health records (EHR) (e.g. human knockout experiments); drug development: genomic approaches to drug target validation; precision medicine: e.g. DNA integrated into hospital EHR for pre-emptive pharmacogenomics. In late translational research we identified exemplars including: learning health systems with outcome trials integrated into clinical care; citizen driven health with 24/7 multi-parameter patient monitoring to improve outcomes and population-based linkages of multiple EHR sources

Translating Regenerative Biomaterials Into Clinical Practice.

PubMed

Stace, Edward T; Dakin, Stephanie G; Mouthuy, Pierre-Alexis; Carr, Andrew J

2016-01-01

Globally health care spending is increasing unsustainably. This is especially true of the treatment of musculoskeletal (MSK) disease where in the United States the MSK disease burden has doubled over the last 15 years. With an aging and increasingly obese population, the surge in MSK related spending is only set to worsen. Despite increased funding, research and attention to this pressing health need, little progress has been made toward novel therapies. Tissue engineering and regenerative medicine (TERM) strategies could provide the solutions required to mitigate this mounting burden. Biomaterial-based treatments in particular present a promising field of potentially cost-effective therapies. However, the translation of a scientific development to a successful treatment is fraught with difficulties. These barriers have so far limited translation of TERM science into clinical treatments. It is crucial for primary researchers to be aware of the barriers currently restricting the progression of science to treatments. Researchers need to act prospectively to ensure the clinical, financial, and regulatory hurdles which seem so far removed from laboratory science do not stall or prevent the subsequent translation of their idea into a treatment. The aim of this review is to explore the development and translation of new treatments. Increasing the understanding of these complexities and barriers among primary researchers could enhance the efficiency of biomaterial translation. © 2015 Wiley Periodicals, Inc.

Integrating Bioethics into Clinical and Translational Science Research: A Roadmap

PubMed Central

Shapiro, Robyn S.; Layde, Peter M.

2008-01-01

Abstract Recent initiatives to improve human health emphasize the need to effectively and appropriately translate new knowledge gleaned from basic biomedical and behavioral research to clinical and community application. To maximize the beneficial impact of scientific advances in clinical practice and community health, and to guard against potential deleterious medical and societal consequences of such advances, incorporation of bioethics at each stage of clinical and translational science research is essential. At the earliest stage, bioethics input is critical to address issues such as whether to limit certain areas of scientific inquiry. Subsequently, bioethics input is important to assure not only that human subjects trials are conducted and reported responsibly, but also that results are incorporated into clinical and community practices in a way that promotes and protects bioethical principles. At the final stage of clinical and translational science research, bioethics helps to identify the need and approach for refining clinical practices when safety or other concerns arise. The framework we present depicts how bioethics interfaces with each stage of clinical and translational science research, and suggests an important research agenda for systematically and comprehensively assuring bioethics input into clinical and translational science initiatives. PMID:20443821

Targeting inflammation in pancreatic cancer: Clinical translation

PubMed Central

Steele, Colin William; Kaur Gill, Nina Angharad; Jamieson, Nigel Balfour; Carter, Christopher Ross

2016-01-01

Preclinical modelling studies are beginning to aid development of therapies targeted against key regulators of pancreatic cancer progression. Pancreatic cancer is an aggressive, stromally-rich tumor, from which few people survive. Within the tumor microenvironment cellular and extracellular components exist, shielding tumor cells from immune cell clearance, and chemotherapy, enhancing progression of the disease. The cellular component of this microenvironment consists mainly of stellate cells and inflammatory cells. New findings suggest that manipulation of the cellular component of the tumor microenvironment is possible to promote immune cell killing of tumor cells. Here we explore possible immunogenic therapeutic strategies. Additionally extracellular stromal elements play a key role in protecting tumor cells from chemotherapies targeted at the pancreas. We describe the experimental findings and the pitfalls associated with translation of stromally targeted therapies to clinical trial. Finally, we discuss the key inflammatory signal transducers activated subsequent to driver mutations in oncogenic Kras in pancreatic cancer. We present the preclinical findings that have led to successful early trials of STAT3 inhibitors in pancreatic adenocarcinoma. PMID:27096033

Found in translation: Integrating laboratory and clinical oncology research

PubMed Central

Wagner, H

2008-01-01

Translational research in medicine aims to inform the clinic and the laboratory with the results of each other’s work, and to bring promising and validated new therapies into clinical application. While laudable in intent, this is complicated in practice and the current state of translational research in cancer shows both striking success stories and examples of the numerous potential obstacles as well as opportunities for delays and errors in translation. This paper reviews the premises, promises, and problems of translational research with a focus on radiation oncology and suggests opportunities for improvements in future research design. PMID:21611010

Clinical and Translational Epidemiology Branch (CTEB)

Cancer.gov

The Clinical and Translational Epidemiology Branch focuses on factors that influence cancer progression, recurrence, survival, and other treatment outcomes, and factors associated with cancer development.

Gene Editing: Regulatory and Translation to Clinic.

PubMed

Ando, Dale; Meyer, Kathleen

2017-10-01

The clinical application and regulatory strategy of genome editing for ex vivo cell therapy is derived from the intersection of two fields of study: viral vector gene therapy trials; and clinical trials with ex vivo purification and engraftment of CD34 +  hematopoietic stem cells, T cells, and tumor cell vaccines. This article covers the regulatory and translational preclinical activities needed for a genome editing clinical trial modifying hematopoietic stem cells and the genesis of this current strategy based on previous clinical trials using genome-edited T cells. The SB-728 zinc finger nuclease platform is discussed because this is the most clinically advanced genome editing technology. Copyright © 2017 Elsevier Inc. All rights reserved.

Reengineering the National Clinical and Translational Research Enterprise: The Strategic Plan of the National Clinical and Translational Science Awards Consortium

PubMed Central

Reis, Steven E.; Berglund, Lars; Bernard, Gordon R.; Califf, Robert M.; FitzGerald, Garret A.; Johnson, Peter C.

2009-01-01

Advances in human health require the efficient and rapid translation of scientific discoveries into effective clinical treatments; this process in turn depends upon observational data gathered from patients, communities, and public-health research that can be used to guide basic scientific investigation. Such bidirectional translational science, however, faces unprecedented challenges due to the rapid pace of scientific and technological development, as well as the difficulties of negotiating increasingly complex regulatory and commercial environments that overlap the research domain. Further, numerous barriers to translational science have emerged among the nation’s academic research centers, including basic structural and cultural impediments to innovation and collaboration, shortages of trained investigators, and inadequate funding. To address these serious and systemic problems, in 2006, the National Institutes of Health created the Clinical and Translational Science Awards (CTSA) program, which aims to catalyze the transformation of biomedical research at a national level, speeding the discovery and development of therapies, fostering collaboration, engaging communities, and training succeeding generations of clinical and translational researchers. The authors report in detail on the planning process, begun in 2008, that was used to engage stakeholders and to identify, refine, and ultimately implement the CTSA program’s overarching strategic goals. They also discuss the implications and likely impact of this strategic planning process as it is applied among the nation’s academic health centers. PMID:20182119

Reengineering the national clinical and translational research enterprise: the strategic plan of the National Clinical and Translational Science Awards Consortium.

PubMed

Reis, Steven E; Berglund, Lars; Bernard, Gordon R; Califf, Robert M; Fitzgerald, Garret A; Johnson, Peter C

2010-03-01

Advances in human health require the efficient and rapid translation of scientific discoveries into effective clinical treatments; this process, in turn, depends on observational data gathered from patients, communities, and public health research that can be used to guide basic scientific investigation. Such bidirectional translational science, however, faces unprecedented challenges due to the rapid pace of scientific and technological development, as well as the difficulties of negotiating increasingly complex regulatory and commercial environments that overlap the research domain. Further, numerous barriers to translational science have emerged among the nation's academic research centers, including basic structural and cultural impediments to innovation and collaboration, shortages of trained investigators, and inadequate funding.To address these serious and systemic problems, in 2006 the National Institutes of Health created the Clinical and Translational Science Awards (CTSA) program, which aims to catalyze the transformation of biomedical research at a national level, speeding the discovery and development of therapies, fostering collaboration, engaging communities, and training succeeding generations of clinical and translational researchers. The authors report in detail on the planning process, begun in 2008, that was used to engage stakeholders and to identify, refine, and ultimately implement the CTSA program's overarching strategic goals. They also discuss the implications and likely impact of this strategic planning process as it is applied among the nation's academic health centers.

Translational epigenetics: clinical approaches to epigenome therapeutics for cancer.

PubMed

Selcuklu, S Duygu; Spillane, Charles

2008-01-01

Cancer epigenetics research is now entering an exciting phase of translational epigenetics whereby novel epigenome therapeutics is being developed for application in clinical settings. Epigenetics refers to all heritable and potentially reversible changes in gene or genome functioning that occurs without altering the nucleotide sequence of the DNA. A range of different epigenetic "marks" can activate or repress gene expression. While epigenetic alterations are associated with most cancers, epigenetic dysregulation can also have a causal role in cancer etiology. Epigenetically disrupted stem or progenitor cells could have an early role in neoplastic transformations, while perturbance of epigenetic regulatory mechanisms controlling gene expression in cancer-relevant pathways will also be a contribution factor. The reversibility of epigenetic marks provides the possibility that the activity of key cancer genes and pathways can be regulated as a therapeutic approach. The growing availability of a range of chemical agents which can affect epigenome functioning has led to a range of epigenetic-therapeutic approaches for cancer and intense interest in the development of second-generation epigenetic drugs (epi-drugs) which would have greater specificity and efficacy in clinical settings. The latest developments in this exciting arena of translational cancer epigenetics were presented at a recent conference on "Epigenetics and New Therapies in Cancer" at the Spanish National Cancer Research Center (CNIO), Spain.

Translation and cross-cultural adaptation of the Clinical Competence Questionnaire for use in Brazil 1

PubMed Central

Kwiatkoski, Danielle Ritter; Mantovani, Maria de Fátima; Pereira, Evani Marques; Bortolato-Major, Carina; Mattei, Ângela Taís; Peres, Aida Maris

2017-01-01

ABSTRACT Objective: translating and transculturally adapting the Clinical Competence Questionnaire to Brazilian senior undergraduate Nursing students, as well as measuring psychometric properties of the questionnaire. Method: a methodological study carried out in six steps: translation of the Clinical Competence Questionnaire instrument, consensus of the translations, back-translation, analysis by an expert committee, pre-testing and then presentation of the cross-cultural adaptation process to the developers. Psychometric properties were measured using Cronbach's alpha, intraclass correlation coefficient and content validity index. Results: the instrument was translated, transculturally adapted and its final version consisted of 48 items. Cronbach's alpha coefficient was 0.90, and the agreement index of the items was 99% for students and 98% for evaluators. Conclusion: the Clinical Competence Questionnaire was translated and adapted to Brazilian students, and the psychometric properties of the Portuguese version of the questionnaire presented satisfactory internal consistency regarding the studied sample. PMID:28591303

The Role of the Clinical and Translational Science Awards Program in Improving the Quality and Efficiency of Clinical Research

PubMed Central

Rosenblum, Daniel

2011-01-01

Recognizing the need to increase the efficiency and quality of translating basic discovery into treatment and prevention strategies for patients and the public, the National Institutes of Health (NIH) announced the Clinical and Translational Science Awards (CTSAs) in 2006. Academic health centers that competed successfully for these awards agreed to work as a consortium and in cooperation with the NIH to improve the translation process by training the next generation of investigators to work in interdisciplinary teams, developing public-private partnerships in the movement of basic discovery to preclinical and clinical studies and trials, improving clinical research management, and engaging with communities to ensure their involvement in shaping research questions and in implementing research results. The CTSAs have addressed the crucial need to improve the quality and efficiency of clinical research by (1) providing training for clinical investigators and for bench researchers to facilitate their participation in the clinical and translational research environment, (2) developing more systematic approaches to clinical research management, and (3) engaging communities as active participants in the design and conduct of clinical research studies and trials and as leaders in implementing health advances that are of high importance to them. We provide an overview of the CTSA activities with attention to these three areas, which are essential to developing efficient clinical research efforts and effective implementation of research results on a national level. PMID:21896519

Preclinical to Clinical Translation of Studies of Transcranial Direct-Current Stimulation in the Treatment of Epilepsy: A Systematic Review

PubMed Central

Regner, Gabriela G.; Pereira, Patrícia; Leffa, Douglas T.; de Oliveira, Carla; Vercelino, Rafael; Fregni, Felipe; Torres, Iraci L. S.

2018-01-01

Epilepsy is a chronic brain syndrome characterized by recurrent seizures resulting from excessive neuronal discharges. Despite the development of various new antiepileptic drugs, many patients are refractory to treatment and report side effects. Non-invasive methods of brain stimulation, such as transcranial direct current stimulation (tDCS), have been tested as alternative approaches to directly modulate the excitability of epileptogenic neural circuits. Although some pilot and initial clinical studies have shown positive results, there is still uncertainty regarding the next steps of investigation in this field. Therefore, we reviewed preclinical and clinical studies using the following framework: (1) preclinical studies that have been successfully translated to clinical studies, (2) preclinical studies that have failed to be translated to clinical studies, and (3) clinical findings that were not previously tested in preclinical studies. We searched PubMed, Web of Science, Embase, and SciELO (2002–2017) using the keywords “tDCS,” “epilepsy,” “clinical trials,” and “animal models.” Our initial search resulted in 64 articles. After applying inclusion and exclusion criteria, we screened 17 full-text articles to extract findings about the efficacy of tDCS, with respect to the therapeutic framework used and the resulting reduction in seizures and epileptiform patterns. We found that few preclinical findings have been translated into clinical research (number of sessions and effects on seizure frequency) and that most findings have not been tested clinically (effects of tDCS on status epilepticus and absence epilepsy, neuroprotective effects in the hippocampus, and combined use with specific medications). Finally, considering that clinical studies on tDCS have been conducted for several epileptic syndromes, most were not previously tested in preclinical studies (Rasmussen's encephalitis, drug resistant epilepsy, and hippocampal sclerosis

Do clinical and translational science graduate students understand linear regression? Development and early validation of the REGRESS quiz.

PubMed

Enders, Felicity

2013-12-01

Although regression is widely used for reading and publishing in the medical literature, no instruments were previously available to assess students' understanding. The goal of this study was to design and assess such an instrument for graduate students in Clinical and Translational Science and Public Health. A 27-item REsearch on Global Regression Expectations in StatisticS (REGRESS) quiz was developed through an iterative process. Consenting students taking a course on linear regression in a Clinical and Translational Science program completed the quiz pre- and postcourse. Student results were compared to practicing statisticians with a master's or doctoral degree in statistics or a closely related field. Fifty-two students responded precourse, 59 postcourse , and 22 practicing statisticians completed the quiz. The mean (SD) score was 9.3 (4.3) for students precourse and 19.0 (3.5) postcourse (P < 0.001). Postcourse students had similar results to practicing statisticians (mean (SD) of 20.1(3.5); P = 0.21). Students also showed significant improvement pre/postcourse in each of six domain areas (P < 0.001). The REGRESS quiz was internally reliable (Cronbach's alpha 0.89). The initial validation is quite promising with statistically significant and meaningful differences across time and study populations. Further work is needed to validate the quiz across multiple institutions. © 2013 Wiley Periodicals, Inc.

A comparative analysis of acute-phase proteins as inflammatory biomarkers in preclinical toxicology studies: implications for preclinical to clinical translation.

PubMed

Watterson, Claire; Lanevschi, Anne; Horner, Judith; Louden, Calvert

2009-01-01

Recently, in early clinical development, a few biologics and small molecules intended as antitumor or anti-inflammatory agents have caused a severe adverse pro-inflammatory systemic reaction also known as systemic inflammatory response syndrome (SIRS). This toxicity could result from expected pharmacological effects of a therapeutic antibody and/or from interaction with antigens expressed on cells/tissues other than the intended target. Clinical monitoring of SIRS is challenging because of the narrow diagnostic window to institute a successful intervening therapeutic strategy prior to acute circulatory collapse. Furthermore, for these classes of therapeutic agents, studies in animals have low predictive ability to identify potential human hazards. In vitro screens with human cells, though promising, need further development. Therefore, identification of improved preclinical diagnostic markers of SIRS will enable clinicians to select applicable markers for clinical testing and avoid potentially catastrophic events. There is limited preclinical toxicology data describing the interspecies performance of acute-phase proteins because the response time, type, and duration of major acute-phase proteins vary significantly between species. This review will attempt to address this intellectual gap, as well as the use and applicability of acute-phase proteins as preclinical to clinical translational biomarkers of SIRS.

Ensuring Cross-Cultural Equivalence in Translation of Research Consents and Clinical Documents

PubMed Central

Lee, Cheng-Chih; Li, Denise; Arai, Shoshana; Puntillo, Kathleen

2010-01-01

The aim of this article is to describe a formal process used to translate research study materials from English into traditional Chinese characters. This process may be useful for translating documents for use by both research participants and clinical patients. A modified Brislin model was used as the systematic translation process. Four bilingual translators were involved, and a Flaherty 3-point scale was used to evaluate the translated documents. The linguistic discrepancies that arise in the process of ensuring cross-cultural congruency or equivalency between the two languages are presented to promote the development of patient-accessible cross-cultural documents. PMID:18948451

Translational bioinformatics: linking the molecular world to the clinical world.

PubMed

Altman, R B

2012-06-01

Translational bioinformatics represents the union of translational medicine and bioinformatics. Translational medicine moves basic biological discoveries from the research bench into the patient-care setting and uses clinical observations to inform basic biology. It focuses on patient care, including the creation of new diagnostics, prognostics, prevention strategies, and therapies based on biological discoveries. Bioinformatics involves algorithms to represent, store, and analyze basic biological data, including DNA sequence, RNA expression, and protein and small-molecule abundance within cells. Translational bioinformatics spans these two fields; it involves the development of algorithms to analyze basic molecular and cellular data with an explicit goal of affecting clinical care.

The CTSA Consortium's Catalog of Assets for Translational and Clinical Health Research (CATCHR)

PubMed Central

Mapes, Brandy; Basford, Melissa; Zufelt, Anneliese; Wehbe, Firas; Harris, Paul; Alcorn, Michael; Allen, David; Arnim, Margaret; Autry, Susan; Briggs, Michael S.; Carnegie, Andrea; Chavis‐Keeling, Deborah; De La Pena, Carlos; Dworschak, Doris; Earnest, Julie; Grieb, Terri; Guess, Marilyn; Hafer, Nathaniel; Johnson, Tesheia; Kasper, Amanda; Kopp, Janice; Lockie, Timothy; Lombardo, Vincetta; McHale, Leslie; Minogue, Andrea; Nunnally, Beth; O'Quinn, Deanna; Peck, Kelly; Pemberton, Kieran; Perry, Cheryl; Petrie, Ginny; Pontello, Andria; Posner, Rachel; Rehman, Bushra; Roth, Deborah; Sacksteder, Paulette; Scahill, Samantha; Schieri, Lorri; Simpson, Rosemary; Skinner, Anne; Toussant, Kim; Turner, Alicia; Van der Put, Elaine; Wasser, June; Webb, Chris D.; Williams, Maija; Wiseman, Lori; Yasko, Laurel; Pulley, Jill

2014-01-01

Abstract The 61 CTSA Consortium sites are home to valuable programs and infrastructure supporting translational science and all are charged with ensuring that such investments translate quickly to improved clinical care. Catalog of Assets for Translational and Clinical Health Research (CATCHR) is the Consortium's effort to collect and make available information on programs and resources to maximize efficiency and facilitate collaborations. By capturing information on a broad range of assets supporting the entire clinical and translational research spectrum, CATCHR aims to provide the necessary infrastructure and processes to establish and maintain an open‐access, searchable database of consortium resources to support multisite clinical and translational research studies. Data are collected using rigorous, defined methods, with the resulting information made visible through an integrated, searchable Web‐based tool. Additional easy‐to‐use Web tools assist resource owners in validating and updating resource information over time. In this paper, we discuss the design and scope of the project, data collection methods, current results, and future plans for development and sustainability. With increasing pressure on research programs to avoid redundancy, CATCHR aims to make available information on programs and core facilities to maximize efficient use of resources. PMID:24456567

[Related issues in clinical translational application of adipose-derived stem cells].

PubMed

Liu, Hongwei; Cheng, Biao; Fu, Xiaobing

2012-10-01

To introduce the related issues in the clinical translational application of adipose-derived stem cells (ASCs). The latest papers were extensively reviewed, concerning the issues of ASCs production, management, transportation, use, and safety during clinical application. ASCs, as a new member of adult stem cells family, bring to wide application prospect in the field of regenerative medicine. Over 40 clinical trials using ASCs conducted in 15 countries have been registered on the website (http://www.clinicaltrials.gov) of the National Institutes of Health (NIH), suggesting that ASCs represents a promising approach to future cell-based therapies. In the clinical translational application, the related issues included the quality control standard that management and production should follow, the prevention measures of pathogenic microorganism pollution, the requirements of enzymes and related reagent in separation process, possible effect of donor site, age, and sex in sampling, low temperature storage, product transportation, and safety. ASCs have the advantage of clinical translational application, much attention should be paid to these issues in clinical application to accelerate the clinical translation process.

Actinic keratosis modelling in mice: A translational study

PubMed Central

Vandenberghe, Isabelle; Cartron, Valérie; Cèbe, Patrick; Blanchet, Jean-Christophe; Sibaud, Vincent; Guilbaud, Nicolas; Audoly, Laurent; Lamant, Laurence; Kruczynski, Anna

2017-01-01

Background Actinic keratoses (AK) are pre-malignant cutaneous lesions caused by prolonged exposure to ultraviolet radiation. As AKs lesions are generally accepted to be the initial lesions in a disease continuum that progresses to squamous cell carcinoma (SCC), AK lesions have to be treated. They are also the second most common reason for visits to the dermatologist. Several treatments are available but their efficacy still needs to be improved. The UV-B-induced KA lesion mouse model is used in preclinical studies to assess the efficacy of novel molecules, even though it is often more representative of advanced AK or SCC. Objectives Here we report on a translational study, comparing the various stages of AK development in humans and in the UV-B irradiated mouse model, as well as the optimization of photograph acquisition of AK lesions on mouse skin. Methods Human and mouse skin lesions were analysed by histology and immunohistochemistry. Mouse lesions were also assessed using a digital dermatoscope. Results An histological and phenotypic analysis, including p53, Ki67 and CD3 expression detection, performed on human and mouse AK lesions, shows that overall AK modelling in mice is relevant in the clinical situation. Some differences are observed, such as disorganization of keratinocytes of the basal layer and a number of atypical nuclei which are more numerous in human AK, whereas much more pronounced acanthosis is observed in skin lesion in mice. Thanks to this translational study, we are able to select appropriate experimental conditions for establishing either early or advanced stage AK or an SCC model. Furthermore, we optimized photograph acquisition of AK lesions on mouse skin by using a digital dermatoscope which is also used in clinics and allows reproducible photograph acquisition for further reliable assessment of mouse lesions. Use of this camera is illustrated through a pharmacological study assessing the activity of CARAC®. Conclusion These data

Clinical and translational research capacity building needs in minority medical and health science Hispanic institutions.

PubMed

Estapé-Garrastazu, Estela S; Noboa-Ramos, Carlamarie; De Jesús-Ojeda, Lizbelle; De Pedro-Serbiá, Zulmarie; Acosta-Pérez, Edna; Camacho-Feliciano, Delia M

2014-10-01

A preliminary needs assessment was conducted among faculty and students of three minority medical and health science institutions comprising the Puerto Rico Clinical and Translational Research Consortium (PRCTRC). The Web-based survey was focused on evaluating the training interests in the clinical and translational research core areas and competencies developed by the National Institutes of Health-Clinical and Translational Sciences Award. The survey was the result of a team effort of three PRCTRC key function's leaderships: Multidisciplinary Training and Career Development, Tracking and Evaluation and Community Research and Engagement. The questionnaire included 45 items distributed across five content areas including demographics, research training needs, training activities coordination and knowledge about the services offered by the PRCTRC. Analysis of research needs includes a sample distribution according to professor, assistant/associate professor and graduate students. The thematic area with highest response rate among the three groups was: "Identify major clinical/public health problems and relevant translational research questions," with the competency "Identify basic and preclinical studies that are potential testable clinical research hypothesis." These preliminary results will guide the training and professional development of the new generation of clinical and translational researchers needed to eliminate health disparities. © 2014 The Authors. Clinical and Translational Science Published by Wiley Periodicals, Inc.

Deriving Competencies for Mentors of Clinical and Translational Scholars

PubMed Central

Abedin, Zainab; Biskup, Ewelina; Silet, Karin; Garbutt, Jane M.; Kroenke, Kurt; Feldman, Mitchell D.; McGee, Jr, Richard; Fleming, Michael; Pincus, Harold Alan

2012-01-01

Abstract Although the importance of research mentorship has been well established, the role of mentors of junior clinical and translational science investigators is not clearly defined. The authors attempt to derive a list of actionable competencies for mentors from a series of complementary methods. We examined focus groups, the literature, competencies derived for clinical and translational scholars, mentor training curricula, mentor evaluation forms and finally conducted an expert panel process in order to compose this list. These efforts resulted in a set of competencies that include generic competencies expected of all mentors, competencies specific to scientists, and competencies that are clinical and translational research specific. They are divided into six thematic areas: (1) Communication and managing the relationship, (2) Psychosocial support, (3) Career and professional development, (4) Professional enculturation and scientific integrity, (5) Research development, and (6) Clinical and translational investigator development. For each thematic area, we have listed associated competencies, 19 in total. For each competency, we list examples that are actionable and measurable. Although a comprehensive approach was used to derive this list of competencies, further work will be required to parse out how to apply and adapt them, as well future research directions and evaluation processes. Clin Trans Sci 2012; Volume 5: 273–280 PMID:22686206

The Serotonin Transporter and Early Life Stress: Translational Perspectives

PubMed Central

Houwing, Danielle J.; Buwalda, Bauke; van der Zee, Eddy A.; de Boer, Sietse F.; Olivier, Jocelien D. A.

2017-01-01

The interaction between the serotonin transporter (SERT) linked polymorphic region (5-HTTLPR) and adverse early life stressing (ELS) events is associated with enhanced stress susceptibility and risk to develop mental disorders like major depression, anxiety, and aggressiveness. In particular, human short allele carriers are at increased risk. This 5-HTTLPR polymorphism is absent in the rodent SERT gene, but heterozygous SERT knockout rodents (SERT+/−) show several similarities to the human S-allele carrier, therefore creating an animal model of the human situation. Many rodent studies investigated ELS interactions in SERT knockout rodents combined with ELS. However, underlying neuromolecular mechanisms of the (mal)adaptive responses to adversity displayed by SERT rodents remain to be elucidated. Here, we provide a comprehensive review including studies describing mechanisms underlying SERT variation × ELS interactions in rodents. Alterations at the level of translation and transcription but also epigenetic alterations considerably contribute to underlying mechanisms of SERT variation × ELS interactions. In particular, SERT+/− rodents exposed to adverse early rearing environment may be of high translational and predictive value to the more stress sensitive human short-allele carrier, considering the similarity in neurochemical alterations. Therefore, SERT+/− rodents are highly relevant in research that aims to unravel the complex psychopathology of mental disorders. So far, most studies fail to show solid evidence for increased vulnerability to develop affective-like behavior after ELS in SERT+/− rodents. Several reasons may underlie these failures, e.g., (1) stressors used might not be optimal or severe enough to induce maladaptations, (2) effects in females are not sufficiently studied, and (3) few studies include both behavioral manifestations and molecular correlates of ELS-induced effects in SERT+/− rodents. Of course, one should not exclude the

Contemporary Translation Theories. Second Revised Edition. Topics in Translation 21.

ERIC Educational Resources Information Center

Gentzler, Edwin

This book traces the growth of translation theory from its traditional roots through the recent proliferation of theories, fueled by research in feminism, poststructural, and postcolonial investigations. It examines 5 new approaches: the North American translation workshop, the science of translation, early translation studies, polysystem theory,…

Bottlenecks to clinical translation of direct brain-computer interfaces.

PubMed

Serruya, Mijail D

2014-01-01

Despite several decades of research into novel brain-implantable devices to treat a range of diseases, only two-cochlear implants for sensorineural hearing loss and deep brain stimulation for movement disorders-have yielded any appreciable clinical benefit. Obstacles to translation include technical factors (e.g., signal loss due to gliosis or micromotion), lack of awareness of current clinical options for patients that the new therapy must outperform, traversing between federal and corporate funding needed to support clinical trials, and insufficient management expertise. This commentary reviews these obstacles preventing the translation of promising new neurotechnologies into clinical application and suggests some principles that interdisciplinary teams in academia and industry could adopt to enhance their chances of success.

Translation failure and medical reversal: Two sides to the same coin.

PubMed

Prasad, Vinay

2016-01-01

Translation failure occurs when the results of preclinical, observational and/or early phase studies fail to predict the results of well done (i.e. appropriately controlled, adequately powered, and properly conducted) phase III or randomised clinical trials. Some failures occur when promising basic science findings fail to replicate in human studies, while others happen when promising uncontrolled trial data show an exaggerated effect that vanishes in the setting of a randomised trial. Medical reversals occur when the results of preclinical, observational and/or early phase studies fail to predict the results of subsequent randomized clinical trials, but the practice has already gained widespread acceptance. Oncologic examples include bevacizumab and the use of autologous stem cell transplant in metastatic breast cancer. In a well-intentioned effort to reduce the rate of translation failure, oncologists must be careful that changes to regulatory processes and clinical trial design do not actually work to increase the approval of ineffective compounds. By trying to cure translation failure, we should be careful to avoid medical reversal. The rise of surrogate end-points and role of hard-wired bias in oncology trials suggest that we may be currently ignoring the simple fact that translation failure and medical reversal are two sides to the same coin. Published by Elsevier Ltd.

Evaluation Guidelines for the Clinical and Translational Science Awards (CTSAs)

PubMed Central

Rubio, Doris M.; Thomas, Veronica G.

2013-01-01

Abstract The National Center for Advancing Translational Sciences (NCATS), a part of the National Institutes of Health, currently funds the Clinical and Translational Science Awards (CTSAs), a national consortium of 61 medical research institutions in 30 states and the District of Columbia. The program seeks to transform the way biomedical research is conducted, speed the translation of laboratory discoveries into treatments for patients, engage communities in clinical research efforts, and train a new generation of clinical and translational researchers. An endeavor as ambitious and complex as the CTSA program requires high‐quality evaluations in order to show that the program is well implemented, efficiently managed, and demonstrably effective. In this paper, the Evaluation Key Function Committee of the CTSA Consortium presents an overall framework for evaluating the CTSA program and offers policies to guide the evaluation work. The guidelines set forth are designed to serve as a tool for education within the CTSA community by illuminating key issues and practices that should be considered during evaluation planning, implementation, and utilization. Additionally, these guidelines can provide a basis for ongoing discussions about how the principles articulated in this paper can most effectively be translated into operational reality. PMID:23919366

Translational medicine: science or wishful thinking?

PubMed Central

Wehling, Martin

2008-01-01

"Translational medicine" as a fashionable term is being increasingly used to describe the wish of biomedical researchers to ultimately help patients. Despite increased efforts and investments into R&D, the output of novel medicines has been declining dramatically over the past years. Improvement of translation is thought to become a remedy as one of the reasons for this widening gap between input and output is the difficult transition between preclinical ("basic") and clinical stages in the R&D process. Animal experiments, test tube analyses and early human trials do simply not reflect the patient situation well enough to reliably predict efficacy and safety of a novel compound or device. This goal, however, can only be achieved if the translational processes are scientifically backed up by robust methods some of which still need to be developed. This mainly relates to biomarker development and predictivity assessment, biostatistical methods, smart and accelerated early human study designs and decision algorithms among other features. It is therefore claimed that a new science needs to be developed called 'translational science in medicine'. PMID:18559092

Large animal models in experimental knee sports surgery: focus on clinical translation.

PubMed

Madry, Henning; Ochi, Mitsuo; Cucchiarini, Magali; Pape, Dietrich; Seil, Romain

2015-12-01

Large animal models play a crucial role in sports surgery of the knee, as they are critical for the exploration of new experimental strategies and the clinical translation of novel techniques. The purpose of this contribution is to provide critical aspects of relevant animal models in this field, with a focus on paediatric anterior cruciate ligament (ACL) reconstruction, high tibial osteotomy, and articular cartilage repair. Although there is no single large animal model strictly replicating the human knee joint, the sheep stifle joint shares strong similarities. Studies in large animal models of paediatric ACL reconstruction identified specific risk factors associated with the different surgical techniques. The sheep model of high tibial osteotomy is a powerful new tool to advance the understanding of the effect of axial alignment on the lower extremity on specific issues of the knee joint. Large animal models of both focal chondral and osteochondral defects and of osteoarthritis have brought new findings about the mechanisms of cartilage repair and treatment options. The clinical application of a magnetic device for targeted cell delivery serves as a suitable example of how data from such animal models are directly translated into in clinical cartilage repair. As novel insights from studies in these translational models will advance the basic science, close cooperation in this important field of clinical translation will improve current reconstructive surgical options and open novel avenues for regenerative therapies of musculoskeletal disorders.

Development and promotion in translational medicine: perspectives from 2012 sino-american symposium on clinical and translational medicine

PubMed Central

2012-01-01

Background Clinical translational medicine (CTM) is an emerging area comprising multidisciplinary research from basic science to medical applications and entails a close collaboration among hospital, academia and industry. Findings This Session focused discussing on new models for project development and promotion in translational medicine. The conference stimulated the scientific and commercial communication of project development between academies and companies, shared the advanced knowledge and expertise of clinical applications, and created the environment for collaborations. Conclusions Although strategic collaborations between corporate and academic institutions have resulted in a state of resurgence in the market, new cooperation models still need time to tell whether they will improve the translational medicine process. PMID:23369198

Designing Biomedical Informatics Infrastructure for Clinical and Translational Science

ERIC Educational Resources Information Center

La Paz Lillo, Ariel Isaac

2009-01-01

Clinical and Translational Science (CTS) rests largely on information flowing smoothly at multiple levels, in multiple directions, across multiple locations. Biomedical Informatics (BI) is seen as a backbone that helps to manage information flows for the translation of knowledge generated and stored in silos of basic science into bedside…

The ecosystem that powered the translation of OCT from fundamental research to clinical and commercial impact [Invited

PubMed Central

Swanson, Eric A.; Fujimoto, James G.

2017-01-01

25 years is a relatively short period of time for a medical technology to become a standard of care impacting the treatment of millions of people every year. Yet 25 years ago there were no OCT companies, no OCT products, no OCT markets, and only one journal article published using the term OCT (optical coherence tomography). OCT has had a tremendous scientific, clinical, and economic impact on society. Today, it is estimated that there are ~30 Million OCT imaging procedures performed worldwide every year and the OCT system market is approaching $1B per year. OCT has helped diagnose patients with retinal disease at early treatable stages, preventing or greatly reducing irreversible vision loss. The technology has facilitated pharmaceutical development and contributed to fundamental understanding of disease mechanisms in multiple fields. The invention and translation of OCT from fundamental research to daily clinical practice would not have been possible without a complex ecosystem involving interaction among physics, engineering, and clinical medicine; government funding of fundamental and clinical research; collaborative and competitive research in the academic sector; entrepreneurship and industry; addressing real clinical needs; harnessing the innovation that occurs at the boundaries of disciplines; and economic and societal impact. This invited review paper discusses the translation of OCT from fundamental research to clinical practice and commercial impact, as well as describes the ecosystem that helped power OCT to where it is today and will continue to drive future advances. While OCT is an example of a technology that has had a powerful impact, there are many biomedical technologies which are poised for translation to clinical practice, and it is our hope that highlighting this ecosystem will help accelerate their translation and clinical impact. PMID:28663854

The ecosystem that powered the translation of OCT from fundamental research to clinical and commercial impact [Invited].

PubMed

Swanson, Eric A; Fujimoto, James G

2017-03-01

25 years is a relatively short period of time for a medical technology to become a standard of care impacting the treatment of millions of people every year. Yet 25 years ago there were no OCT companies, no OCT products, no OCT markets, and only one journal article published using the term OCT (optical coherence tomography). OCT has had a tremendous scientific, clinical, and economic impact on society. Today, it is estimated that there are ~30 Million OCT imaging procedures performed worldwide every year and the OCT system market is approaching $1B per year. OCT has helped diagnose patients with retinal disease at early treatable stages, preventing or greatly reducing irreversible vision loss. The technology has facilitated pharmaceutical development and contributed to fundamental understanding of disease mechanisms in multiple fields. The invention and translation of OCT from fundamental research to daily clinical practice would not have been possible without a complex ecosystem involving interaction among physics, engineering, and clinical medicine; government funding of fundamental and clinical research; collaborative and competitive research in the academic sector; entrepreneurship and industry; addressing real clinical needs; harnessing the innovation that occurs at the boundaries of disciplines; and economic and societal impact. This invited review paper discusses the translation of OCT from fundamental research to clinical practice and commercial impact, as well as describes the ecosystem that helped power OCT to where it is today and will continue to drive future advances. While OCT is an example of a technology that has had a powerful impact, there are many biomedical technologies which are poised for translation to clinical practice, and it is our hope that highlighting this ecosystem will help accelerate their translation and clinical impact.

Early-life stress origins of gastrointestinal disease: animal models, intestinal pathophysiology, and translational implications

PubMed Central

Pohl, Calvin S.; Medland, Julia E.

2015-01-01

Early-life stress and adversity are major risk factors in the onset and severity of gastrointestinal (GI) disease in humans later in life. The mechanisms by which early-life stress leads to increased GI disease susceptibility in adult life remain poorly understood. Animal models of early-life stress have provided a foundation from which to gain a more fundamental understanding of this important GI disease paradigm. This review focuses on animal models of early-life stress-induced GI disease, with a specific emphasis on translational aspects of each model to specific human GI disease states. Early postnatal development of major GI systems and the consequences of stress on their development are discussed in detail. Relevant translational differences between species and models are highlighted. PMID:26451004

Ontology driven integration platform for clinical and translational research

PubMed Central

Mirhaji, Parsa; Zhu, Min; Vagnoni, Mattew; Bernstam, Elmer V; Zhang, Jiajie; Smith, Jack W

2009-01-01

Semantic Web technologies offer a promising framework for integration of disparate biomedical data. In this paper we present the semantic information integration platform under development at the Center for Clinical and Translational Sciences (CCTS) at the University of Texas Health Science Center at Houston (UTHSC-H) as part of our Clinical and Translational Science Award (CTSA) program. We utilize the Semantic Web technologies not only for integrating, repurposing and classification of multi-source clinical data, but also to construct a distributed environment for information sharing, and collaboration online. Service Oriented Architecture (SOA) is used to modularize and distribute reusable services in a dynamic and distributed environment. Components of the semantic solution and its overall architecture are described. PMID:19208190

Is knowledge translation adequate? A quality assurance study of staging investigations in early stage breast cancer patients.

PubMed

Han, Dolly; Hogeveen, Sophie; Sweet Goldstein, Miriam; George, Ralph; Brezden-Masley, Christine; Hoch, Jeffrey; Haq, Rashida; Simmons, Christine E

2012-02-01

After primary surgery, patients diagnosed with early stage breast cancer undergo radiological investigations based on pathologic stage of disease to rule out distant metastases. Published guidelines can aid clinicians in determining which tests are appropriate based on stage of disease. We wished to assess the consistency of radiological staging in an academic community oncology setting with standard guidelines and to determine the overall impact of non-adherence to these guidelines. A retrospective cohort study was conducted for new breast cancer patients seen at a single institution between January 2009 and April 2010. Patients were included if initial diagnosis and primary surgery was at this institution. Pathologic stage and radiological tests completed were recorded. A literature review was performed and the results were compared with those from this study to determine overall adherence rates. Subsequently, a cost analysis was performed to determine the financial impact at this centre. 231 patients met eligibility criteria for inclusion in this study. A large proportion of patients were over-staged with 129 patients (55%) undergoing unnecessary investigations according to guidelines. Specifically, 59% of stage I patients and 58% of stage II patients were over-investigated. Distant metastases at the time of diagnosis were found in three patients, all of whom had stage III disease (1.3%). The literature reviewed revealed similar non-adherence rates in other centres. The estimated cost of such non-adherence is in the range of $78 (CDN) per new early stage breast cancer patient seen at this centre. This oncology centre has a low adherence to practice guidelines for staging investigations in breast cancer patients, with 55% of patients undergoing unnecessary tests. Very few patients had metastases at diagnosis, and all had pathological stage III disease. Efforts may need to focus on improving knowledge translation across clinical oncology settings to increase

Strategies for Derisking Translational Processes for Biomedical Technologies.

PubMed

Abou-El-Enein, Mohamed; Duda, Georg N; Gruskin, Elliott A; Grainger, David W

2017-02-01

Inefficient translational processes for technology-oriented biomedical research have led to some prominent and frequent failures in the development of many leading drug candidates, several designated investigational drugs, and some medical devices, as well as documented patient harm and postmarket product withdrawals. Derisking this process, particularly in the early stages, should increase translational efficiency and streamline resource utilization, especially in an academic setting. In this opinion article, we identify a 12-step guideline for reducing risks typically associated with translating medical technologies as they move toward prototypes, preclinical proof of concept, and possible clinical testing. Integrating the described 12-step process should prove valuable for improving how early-stage academic biomedical concepts are cultivated, culled, and manicured toward intended clinical applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

Towards clinically translatable in vivo nanodiagnostics

NASA Astrophysics Data System (ADS)

Park, Seung-Min; Aalipour, Amin; Vermesh, Ophir; Yu, Jung Ho; Gambhir, Sanjiv S.

2017-05-01

Nanodiagnostics as a field makes use of fundamental advances in nanobiotechnology to diagnose, characterize and manage disease at the molecular scale. As these strategies move closer to routine clinical use, a proper understanding of different imaging modalities, relevant biological systems and physical properties governing nanoscale interactions is necessary to rationally engineer next-generation bionanomaterials. In this Review, we analyse the background physics of several clinically relevant imaging modalities and their associated sensitivity and specificity, provide an overview of the materials currently used for in vivo nanodiagnostics, and assess the progress made towards clinical translation. This work provides a framework for understanding both the impressive progress made thus far in the nanodiagnostics field as well as presenting challenges that must be overcome to obtain widespread clinical adoption.

Early-life stress origins of gastrointestinal disease: animal models, intestinal pathophysiology, and translational implications.

PubMed

Pohl, Calvin S; Medland, Julia E; Moeser, Adam J

2015-12-15

Early-life stress and adversity are major risk factors in the onset and severity of gastrointestinal (GI) disease in humans later in life. The mechanisms by which early-life stress leads to increased GI disease susceptibility in adult life remain poorly understood. Animal models of early-life stress have provided a foundation from which to gain a more fundamental understanding of this important GI disease paradigm. This review focuses on animal models of early-life stress-induced GI disease, with a specific emphasis on translational aspects of each model to specific human GI disease states. Early postnatal development of major GI systems and the consequences of stress on their development are discussed in detail. Relevant translational differences between species and models are highlighted. Copyright © 2015 the American Physiological Society.

Tissue engineered constructs: perspectives on clinical translation.

PubMed

Lu, Lichun; Arbit, Harvey M; Herrick, James L; Segovis, Suzanne Glass; Maran, Avudaiappan; Yaszemski, Michael J

2015-03-01

In this article, a "bedside to bench and back" approach for developing tissue engineered medical products (TEMPs) for clinical applications is reviewed. The driving force behind this approach is unmet clinical needs. Preclinical research, both in vitro and in vivo using small and large animal models, will help find solutions to key research questions. In clinical research, ethical issues regarding the use of cells and tissues, their sources, donor consent, as well as clinical trials are important considerations. Regulatory issues, at both institutional and government levels, must be addressed prior to the translation of TEMPs to clinical practice. TEMPs are regulated as drugs, biologics, devices, or combination products by the U.S. Food and Drug Administration (FDA). Depending on the mode of regulation, applications for TEMP introduction must be filed with the FDA to demonstrate safety and effectiveness in premarket clinical studies, followed by 510(k) premarket clearance or premarket approval (for medical devices), biologics license application approval (for biologics), or new drug application approval (for drugs). A case study on nerve cuffs is presented to illustrate the regulatory process. Finally, perspectives on commercialization such as finding a company partner and funding issues, as well as physician culture change, are presented.

Tissue Engineered Constructs: Perspectives on Clinical Translation

PubMed Central

Lu, Lichun; Arbit, Harvey M.; Herrick, James L.; Segovis, Suzanne Glass; Maran, Avudaiappan; Yaszemski, Michael J.

2015-01-01

In this article, a “bedside to bench and back” approach for developing tissue engineered medical products (TEMPs) for clinical applications is reviewed. The driving force behind this approach is unmet clinical needs. Preclinical research, both in vitro and in vivo using small and large animal models, will help find solutions to key research questions. In clinical research, ethical issues regarding the use of cells and tissues, their sources, donor consent, as well as clinical trials are important considerations. Regulatory issues, at both institutional and government levels, must be addressed prior to the translation of TEMPs to clinical practice. TEMPs are regulated as drugs, biologics, devices, or combination products by the US Food and Drug Administration (FDA). Depending on the mode of regulation, applications for TEMP introduction must be filed with the FDA to demonstrate safety and effectiveness in premarket clinical studies, followed by 510(k) premarket clearance or premarket approval (for medical devices), biologics license application approval (for biologics), or New Drug Application approval (for drugs). A case study on nerve cuffs is presented to illustrate the regulatory process. Finally, perspectives on commercialization such as finding a company partner and funding issues, as well as physician culture change, are presented. PMID:25711151

Molecular imaging of prostate cancer: translating molecular biology approaches into the clinical realm.

PubMed

Vargas, Hebert Alberto; Grimm, Jan; F Donati, Olivio; Sala, Evis; Hricak, Hedvig

2015-05-01

The epidemiology of prostate cancer has dramatically changed since the introduction of prostate-specific antigen (PSA) screening in the 1980's. Most prostate cancers today are detected at early stages of the disease and are considered 'indolent'; however, some patients' prostate cancers demonstrate a more aggressive behaviour which leads to rapid progression and death. Increasing understanding of the biology underlying the heterogeneity that characterises this disease has led to a continuously evolving role of imaging in the management of prostate cancer. Functional and metabolic imaging techniques are gaining importance as the impact on the therapeutic paradigm has shifted from structural tumour detection alone to distinguishing patients with indolent tumours that can be managed conservatively (e.g., by active surveillance) from patients with more aggressive tumours that may require definitive treatment with surgery or radiation. In this review, we discuss advanced imaging techniques that allow direct visualisation of molecular interactions relevant to prostate cancer and their potential for translation to the clinical setting in the near future. The potential use of imaging to follow molecular events during drug therapy as well as the use of imaging agents for therapeutic purposes will also be discussed. • Advanced imaging techniques allow direct visualisation of molecular interactions in prostate cancer. • MRI/PET, optical and Cerenkov imaging facilitate the translation of molecular biology. • Multiple compounds targeting PSMA expression are currently undergoing clinical translation. • Other targets (e.g., PSA, prostate-stem cell antigen, GRPR) are in development.

Critical periods after stroke study: translating animal stroke recovery experiments into a clinical trial

PubMed Central

Dromerick, Alexander W.; Edwardson, Matthew A.; Edwards, Dorothy F.; Giannetti, Margot L.; Barth, Jessica; Brady, Kathaleen P.; Chan, Evan; Tan, Ming T.; Tamboli, Irfan; Chia, Ruth; Orquiza, Michael; Padilla, Robert M.; Cheema, Amrita K.; Mapstone, Mark E.; Fiandaca, Massimo S.; Federoff, Howard J.; Newport, Elissa L.

2015-01-01

Introduction: Seven hundred ninety-five thousand Americans will have a stroke this year, and half will have a chronic hemiparesis. Substantial animal literature suggests that the mammalian brain has much potential to recover from acute injury using mechanisms of neuroplasticity, and that these mechanisms can be accessed using training paradigms and neurotransmitter manipulation. However, most of these findings have not been tested or confirmed in the rehabilitation setting, in large part because of the challenges in translating a conceptually straightforward laboratory experiment into a meaningful and rigorous clinical trial in humans. Through presentation of methods for a Phase II trial, we discuss these issues and describe our approach. Methods: In rodents there is compelling evidence for timing effects in rehabilitation; motor training delivered at certain times after stroke may be more effective than the same training delivered earlier or later, suggesting that there is a critical or sensitive period for strongest rehabilitation training effects. If analogous critical/sensitive periods can be identified after human stroke, then existing clinical resources can be better utilized to promote recovery. The Critical Periods after Stroke Study (CPASS) is a phase II randomized, controlled trial designed to explore whether such a sensitive period exists. We will randomize 64 persons to receive an additional 20 h of upper extremity therapy either immediately upon rehab admission, 2–3 months after stroke onset, 6 months after onset, or to an observation-only control group. The primary outcome measure will be the Action Research Arm Test (ARAT) at 1 year. Blood will be drawn at up to 3 time points for later biomarker studies. Conclusion: CPASS is an example of the translation of rodent motor recovery experiments into the clinical setting; data obtained from this single site randomized controlled trial will be used to finalize the design of a Phase III trial. PMID

MD-CTS: An integrated terminology reference of clinical and translational medicine.

PubMed

Ray, Will; Finamore, Joe; Rastegar-Mojarad, Majid; Kadolph, Chris; Ye, Zhan; Bohne, Jacquie; Xu, Yin; Burish, Dan; Sondelski, Joshua; Easker, Melissa; Finnegan, Brian; Bartkowiak, Barbara; Smith, Catherine Arnott; Tachinardi, Umberto; Mendonca, Eneida A; Weichelt, Bryan; Lin, Simon M

2016-01-01

New vocabularies are rapidly evolving in the literature relative to the practice of clinical medicine and translational research. To provide integrated access to new terms, we developed a mobile and desktop online reference-Marshfield Dictionary of Clinical and Translational Science (MD-CTS). It is the first public resource that comprehensively integrates Wiktionary (word definition), BioPortal (ontology), Wiki (image reference), and Medline abstract (word usage) information. MD-CTS is accessible at http://spellchecker.mfldclin.edu/. The website provides a broadened capacity for the wider clinical and translational science community to keep pace with newly emerging scientific vocabulary. An initial evaluation using 63 randomly selected biomedical words suggests that online references generally provided better coverage (73%-95%) than paper-based dictionaries (57-71%).

The psychopharmacology of aggressive behavior: a translational approach: part 2: clinical studies using atypical antipsychotics, anticonvulsants, and lithium.

PubMed

Comai, Stefano; Tau, Michael; Pavlovic, Zoran; Gobbi, Gabriella

2012-04-01

Patients experiencing mental disorders are at an elevated risk for developing aggressive behavior. In the past 10 years, the psychopharmacological treatment of aggression has changed dramatically owing to the introduction of atypical antipsychotics on the market and the increased use of anticonvulsants and lithium in the treatment of aggressive patients.This review (second of 2 parts) uses a translational medicine approach to examine the neurobiology of aggression, discussing the major neurotransmitter systems implicated in its pathogenesis (serotonin, glutamate, norepinephrine, dopamine, and γ-aminobutyric acid) and the neuropharmacological rationale for using atypical antipsychotics, anticonvulsants, and lithium in the therapeutics of aggressive behavior. A critical review of all clinical trials using atypical antipsychotics (aripiprazole, clozapine, loxapine, olanzapine, quetiapine, risperidone, ziprasidone, and amisulpride), anticonvulsants (topiramate, valproate, lamotrigine, and gabapentin), and lithium are presented. Given the complex, multifaceted nature of aggression, a multifunctional combined therapy, targeting different receptors, seems to be the best strategy for treating aggressive behavior. This therapeutic strategy is supported by translational studies and a few human studies, even if additional randomized, double-blind, clinical trials are needed to confirm the clinical efficacy of this framework.

Post-recombination early Universe cooling by translation-internal inter-conversion: The role of minor constituents.

PubMed

McCaffery, Anthony J

2015-09-14

Little is known of the mechanism by which H and H2, the principal constituents of the post-re-combination early Universe, cooled sufficiently to permit cluster formation, nucleosynthesis, and, eventually, the formation of structured objects. Radiative decay primarily cools the internal modes of H2, as Δj = - 2 jumps accompany quadrupolar emission. This, however, would be a self-limiting mechanism. In this work, a translational energy cooling mechanism based on collision-induced, translation-to-internal mode conversion, is extended, following an earlier study [A. J. McCaffery and R. J. Marsh, J. Chem. Phys. 139, 234310 (2013)] of ensembles comprising H2 in a H atom bath gas. Here, the possible influence of minor species, such as HD, on this cooling mechanism is investigated. Results suggest that the influence of HD is small but not insignificant. Conversion is very rapid and an overall translation-to-internal energy conversion efficiency of some 5% could be expected. This finding may be of use in the further development of models of this complex phase of early Universe evolution. An unexpected finding in this study was that H2 + HD ensembles are capable of very rapid translation-to-internal conversion with efficiencies of >40% and relaxation rates that appear to be relatively slow. This may have potential as an energy storage mechanism.

Translational nutrition research at UC-Davis – the key role of the clinical and translational science center

USDA-ARS?s Scientific Manuscript database

To better understand the facility and equipment needs for human clinical nutrition research the New York Academy of Sciences presented a symposium. This paper is the result of that symposium and provides information into how clinical nutrition research is conducted at the Clinical and Translational ...

The applicability of Lean and Six Sigma techniques to clinical and translational research.

PubMed

Schweikhart, Sharon A; Dembe, Allard E

2009-10-01

Lean and Six Sigma are business management strategies commonly used in production industries to improve process efficiency and quality. During the past decade, these process improvement techniques increasingly have been applied outside the manufacturing sector, for example, in health care and in software development. This article concerns the potential use of Lean and Six Sigma in improving the processes involved in clinical and translational research. Improving quality, avoiding delays and errors, and speeding up the time to implementation of biomedical discoveries are prime objectives of the National Institutes of Health (NIH) Roadmap for Medical Research and the NIH's Clinical and Translational Science Award program. This article presents a description of the main principles, practices, and methods used in Lean and Six Sigma. Available literature involving applications of Lean and Six Sigma to health care, laboratory science, and clinical and translational research is reviewed. Specific issues concerning the use of these techniques in different phases of translational research are identified. Examples of Lean and Six Sigma applications that are being planned at a current Clinical and Translational Science Award site are provided, which could potentially be replicated elsewhere. We describe how different process improvement approaches are best adapted for particular translational research phases. Lean and Six Sigma process improvement methods are well suited to help achieve NIH's goal of making clinical and translational research more efficient and cost-effective, enhancing the quality of the research, and facilitating the successful adoption of biomedical research findings into practice.

Translational informatics: an industry perspective.

PubMed

Cantor, Michael N

2012-01-01

Translational informatics (TI) is extremely important for the pharmaceutical industry, especially as the bar for regulatory approval of new medications is set higher and higher. This paper will explore three specific areas in the drug development lifecycle, from tools developed by precompetitive consortia to standardized clinical data collection to the effective delivery of medications using clinical decision support, in which TI has a major role to play. Advancing TI will require investment in new tools and algorithms, as well as ensuring that translational issues are addressed early in the design process of informatics projects, and also given higher weight in funding or publication decisions. Ultimately, the source of translational tools and differences between academia and industry are secondary, as long as they move towards the shared goal of improving health.

Italian translation and cultural adaptation of the communication assessment tool in an outpatient surgical clinic.

PubMed

Scala, Daniela; Menditto, Enrica; Armellino, Mariano Fortunato; Manguso, Francesco; Monetti, Valeria Marina; Orlando, Valentina; Antonino, Antonio; Makoul, Gregory; De Palma, Maurizio

2016-04-29

The aim of the study is to translate and cross-culturally adapt, for use in the Italian context, the Communication Assessment Tool (CAT) developed by Makoul and colleagues. The study was performed in the out-patient clinic of the Surgical Department of Cardarelli Hospital in Naples, Italy. It involved a systematic, standardized, multi-step process adhering to internationally accepted and recommended guidelines. Corrections and adjustments to the translation addressed both linguistic factors and cultural components. The CAT was translated into Italian by two independent Italian mother-tongue translators. The consensus version was then back-translated by an English mother-tongue translator. This translation process was followed by a consensus meeting between the authors of translation and investigators, and then by two comprehension tests on a total of 65 patients. Results of the translation and cross-cultural adaptation were satisfactory and indicate that the Italian translation of the CAT can be used with confidence in the Italian context.

78 FR 60291 - Investigational Device Exemptions for Early Feasibility Medical Device Clinical Studies...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-01

...] Investigational Device Exemptions for Early Feasibility Medical Device Clinical Studies, Including Certain First in Human Studies; Guidance for Industry and Food and Drug Administration Staff; Availability AGENCY... Feasibility Medical Device Clinical Studies, Including Certain First in Human (FIH) Studies.'' Through the...

Translational Research in Alzheimer’s and Prion Diseases

PubMed Central

Di Fede, Giuseppe; Giaccone, Giorgio; Salmona, Mario; Tagliavini, Fabrizio

2017-01-01

Translational neuroscience integrates the knowledge derived by basic neuroscience with the development of new diagnostic and therapeutic tools that may be applied to clinical practice in neurological diseases. This information can be used to improve clinical trial designs and outcomes that will accelerate drug development, and to discover novel biomarkers which can be efficiently employed to early recognize neurological disorders and provide information regarding the effects of drugs on the underlying disease biology. Alzheimer’s disease (AD) and prion disease are two classes of neurodegenerative disorders characterized by incomplete knowledge of the molecular mechanisms underlying their occurrence and the lack of valid biomarkers and effective treatments. For these reasons, the design of therapies that prevent or delay the onset, slow the progression, or improve the symptoms associated to these disorders is urgently needed. During the last few decades, translational research provided a framework for advancing development of new diagnostic devices and promising disease-modifying therapies for patients with prion encephalopathies and AD. In this review, we provide present evidence of how supportive can be the translational approach to the study of dementias and show some results of our preclinical studies which have been translated to the clinical application following the ‘bed-to-bench-and-back’ research model. PMID:29172000

Clinical and translational research in global health and emergency care: a research agenda.

PubMed

Runyon, Michael S; Sawe, Hendry R; Levine, Adam C; Pousson, Amelia; House, Darlene R; Agrawal, Pooja; Osei-Ampofo, Maxwell; Weiner, Scott G; Douglass, Katherine

2013-12-01

As policy-makers increasingly recognize emergency care to be a global health priority, the need for high-quality clinical and translational research in this area continues to grow. As part of the proceedings of the 2013 Academic Emergency Medicine consensus conference, this article discusses the importance of: 1) including clinical and translational research in the initial emergency care development plan, 2) defining the burden of acute disease and the barriers to conducting research in resource-limited settings, 3) assessing the appropriateness and effectiveness of local and global acute care guidelines within the local context, 4) studying the local research infrastructure needs to understand the best methods to build a sustainable research infrastructure, and 5) studying the long-term effects of clinical research programs on health care systems. © 2013 by the Society for Academic Emergency Medicine.

Ethical clinical translation of stem cell interventions for neurologic disease.

PubMed

Cote, David J; Bredenoord, Annelien L; Smith, Timothy R; Ammirati, Mario; Brennum, Jannick; Mendez, Ivar; Ammar, Ahmed S; Balak, Naci; Bolles, Gene; Esene, Ignatius Ngene; Mathiesen, Tiit; Broekman, Marike L

2017-01-17

The application of stem cell transplants in clinical practice has increased in frequency in recent years. Many of the stem cell transplants in neurologic diseases, including stroke, Parkinson disease, spinal cord injury, and demyelinating diseases, are unproven-they have not been tested in prospective, controlled clinical trials and have not become accepted therapies. Stem cell transplant procedures currently being carried out have therapeutic aims, but are frequently experimental and unregulated, and could potentially put patients at risk. In some cases, patients undergoing such operations are not included in a clinical trial, and do not provide genuinely informed consent. For these reasons and others, some current stem cell interventions for neurologic diseases are ethically dubious and could jeopardize progress in the field. We provide discussion points for the evaluation of new stem cell interventions for neurologic disease, based primarily on the new Guidelines for Stem Cell Research and Clinical Translation released by the International Society for Stem Cell Research in May 2016. Important considerations in the ethical translation of stem cells to clinical practice include regulatory oversight, conflicts of interest, data sharing, the nature of investigation (e.g., within vs outside of a clinical trial), informed consent, risk-benefit ratios, the therapeutic misconception, and patient vulnerability. To help guide the translation of stem cells from the laboratory into the neurosurgical clinic in an ethically sound manner, we present an ethical discussion of these major issues at stake in the field of stem cell clinical research for neurologic disease. © 2016 American Academy of Neurology.

Animal models in translational studies of PTSD.

PubMed

Daskalakis, Nikolaos P; Yehuda, Rachel; Diamond, David M

2013-09-01

Understanding the neurobiological mechanisms of post-traumatic stress disorder (PTSD) is of vital importance for developing biomarkers and more effective pharmacotherapy for this disorder. The design of bidirectional translational studies addressing all facets of PTSD is needed. Animal models of PTSD are needed not only to capture the complexity of PTSD behavioral characteristics, but also to address experimentally the influence of variety of factors which might determine an individual's vulnerability or resilience to trauma, e.g., genetic predisposition, early-life experience and social support. The current review covers recent translational approaches to bridge the gap between human and animal PTSD research and to create a framework for discovery of biomarkers and novel therapeutics. Published by Elsevier Ltd.

Eukaryotic Translation Initiation Factor 4E Is a Feed-Forward Translational Coactivator of Transforming Growth Factor β Early Protransforming Events in Breast Epithelial Cells

PubMed Central

Decarlo, Lindsey; Mestel, Celine; Barcellos-Hoff, Mary-Helen

2015-01-01

Eukaryotic translation initiation factor 4E (eIF4E) is overexpressed early in breast cancers in association with disease progression and reduced survival. Much remains to be understood regarding the role of eIF4E in human cancer. We determined, using immortalized human breast epithelial cells, that elevated expression of eIF4E translationally activates the transforming growth factor β (TGF-β) pathway, promoting cell invasion, a loss of cell polarity, increased cell survival, and other hallmarks of early neoplasia. Overexpression of eIF4E is shown to facilitate the selective translation of integrin β1 mRNA, which drives the translationally controlled assembly of a TGF-β receptor signaling complex containing α3β1 integrins, β-catenin, TGF-β receptor I, E-cadherin, and phosphorylated Smad2/3. This receptor complex acutely sensitizes nonmalignant breast epithelial cells to activation by typically substimulatory levels of activated TGF-β. TGF-β can promote cellular differentiation or invasion and transformation. As a translational coactivator of TGF-β, eIF4E confers selective mRNA translation, reprogramming nonmalignant cells to an invasive phenotype by reducing the set point for stimulation by activated TGF-β. Overexpression of eIF4E may be a proinvasive facilitator of TGF-β activity. PMID:25986608

Proteomics boosts translational and clinical microbiology.

PubMed

Del Chierico, F; Petrucca, A; Vernocchi, P; Bracaglia, G; Fiscarelli, E; Bernaschi, P; Muraca, M; Urbani, A; Putignani, L

2014-01-31

The application of proteomics to translational and clinical microbiology is one of the most advanced frontiers in the management and control of infectious diseases and in the understanding of complex microbial systems within human fluids and districts. This new approach aims at providing, by dedicated bioinformatic pipelines, a thorough description of pathogen proteomes and their interactions within the context of human host ecosystems, revolutionizing the vision of infectious diseases in biomedicine and approaching new viewpoints in both diagnostic and clinical management of the patient. Indeed, in the last few years, many laboratories have matured a series of advanced proteomic applications, aiming at providing individual proteome charts of pathogens, with respect to their morph and/or cell life stages, antimicrobial or antimycotic resistance profiling, epidemiological dispersion. Herein, we aim at reviewing the current state-of-the-art on proteomic protocols designed and set-up for translational and diagnostic microbiological purposes, from axenic pathogens' characterization to microbiota ecosystems' full description. The final goal is to describe applications of the most common MALDI-TOF MS platforms to advanced diagnostic issues related to emerging infections, increasing of fastidious bacteria, and generation of patient-tailored phylotypes. This article is part of a Special Issue entitled: Trends in Microbial Proteomics. © 2013. Published by Elsevier B.V. All rights reserved.

Synthesis maps: visual knowledge translation for the CanIMPACT clinical system and patient cancer journeys.

PubMed

Jones, P H; Shakdher, S; Singh, P

2017-04-01

Salient findings and interpretations from the canimpact clinical cancer research study are visually represented in two synthesis maps for the purpose of communicating an integrated presentation of the study to clinical cancer researchers and policymakers. Synthesis maps integrate evidence and expertise into a visual narrative for knowledge translation and communication. A clinical system synthesis map represents the current Canadian primary care and cancer practice systems, proposed as a visual knowledge translation from the mixed-methods canimpact study to inform Canadian clinical research, policy, and practice discourses. Two synthesis maps, drawn together from multiple canimpact investigations and sources, were required to articulate critical differences between the clinical system and patient perspectives. The synthesis map of Canada-wide clinical cancer systems illustrates the relationships between primary care and the full cancer continuum. A patient-centred map was developed to represent the cancer (and primary care) journeys as experienced by breast and colorectal cancer patients.

Understanding context in knowledge translation: a concept analysis study protocol.

PubMed

Squires, Janet E; Graham, Ian D; Hutchinson, Alison M; Linklater, Stefanie; Brehaut, Jamie C; Curran, Janet; Ivers, Noah; Lavis, John N; Michie, Susan; Sales, Anne E; Fiander, Michelle; Fenton, Shannon; Noseworthy, Thomas; Vine, Jocelyn; Grimshaw, Jeremy M

2015-05-01

To conduct a concept analysis of clinical practice contexts (work environments) that facilitate or militate against the uptake of research evidence by healthcare professionals in clinical practice. This will involve developing a clear definition of context by describing its features, domains and defining characteristics. The context where clinical care is delivered influences that care. While research shows that context is important to knowledge translation (implementation), we lack conceptual clarity on what is context, which contextual factors probably modify the effect of knowledge translation interventions (and hence should be considered when designing interventions) and which contextual factors themselves could be targeted as part of a knowledge translation intervention (context modification). Concept analysis. The Walker and Avant concept analysis method, comprised of eight systematic steps, will be used: (1) concept selection; (2) determination of aims; (3) identification of uses of context; (4) determination of defining attributes of context; (5) identification/construction of a model case of context; (6) identification/construction of additional cases of context; (7) identification/construction of antecedents and consequences of context; and (8) definition of empirical referents of context. This study is funded by the Canadian Institutes of Health Research (January 2014). This study will result in a much needed framework of context for knowledge translation, which identifies specific elements that, if assessed and used to tailor knowledge translation activities, will result in increased research use by nurses and other healthcare professionals in clinical practice, ultimately leading to better patient care. © 2014 John Wiley & Sons Ltd.

Clinical translation of controlled protein delivery systems for tissue engineering.

PubMed

Spiller, Kara L; Vunjak-Novakovic, Gordana

2015-04-01

Strategies that utilize controlled release of drugs and proteins for tissue engineering have enormous potential to regenerate damaged organs and tissues. The multiple advantages of controlled release strategies merit overcoming the significant challenges to translation, including high costs and long, difficult regulatory pathways. This review highlights the potential of controlled release of proteins for tissue engineering and regenerative medicine. We specifically discuss treatment modalities that have reached preclinical and clinical trials, with emphasis on controlled release systems for bone tissue engineering, the most advanced application with several products already in clinic. Possible strategies to address translational and regulatory concerns are also discussed.

Organoid Center Strategies for Accelerating Clinical Translation.

PubMed

Takebe, Takanori; Wells, James M; Helmrath, Michael A; Zorn, Aaron M

2018-06-01

The meteoric rise in stem-cell-derived organoid technologies has ushered in a new era of "organoid medicine." Here we discuss how an organoid center can accelerate the translation of laboratory proof-of-principle experiments into clinical practice by developing and utilizing shared platforms for commercial and medical applications. Copyright © 2018 Elsevier Inc. All rights reserved.

Knowledge Translation Interventions to Improve the Timing of Dialysis Initiation: Protocol for a Cluster Randomized Trial.

PubMed

Chau, Elaine M T; Manns, Braden J; Garg, Amit X; Sood, Manish M; Kim, S Joseph; Naimark, David; Nesrallah, Gihad E; Soroka, Steven D; Beaulieu, Monica; Dixon, Stephanie; Alam, Ahsan; Tangri, Navdeep

2016-01-01

Early initiation of chronic dialysis (starting dialysis with higher vs lower kidney function) has risen rapidly in the past 2 decades in Canada and internationally, despite absence of established health benefits and higher costs. In 2014, a Canadian guideline on the timing of dialysis initiation, recommending an intent-to-defer approach, was published. The objective of this study is to evaluate the efficacy and safety of a knowledge translation intervention to promote the intent-to-defer approach in clinical practice. This study is a multicenter, 2-arm parallel, cluster randomized trial. The study involves 55 advanced chronic kidney disease clinics across Canada. Patients older than 18 years who are managed by nephrologists for more than 3 months, and initiate dialysis in the follow-up period are included in the study. Outcomes will be measured at the patient-level and enumerated within a cluster. Data on characteristics of each dialysis start will be determined by linkages with the Canadian Organ Replacement Register. Primary outcomes include the proportion of patients who start dialysis early with an estimated glomerular filtration rate greater than 10.5 mL/min/1.73 m 2 and start dialysis in hospital as inpatients or in an emergency room setting. Secondary outcomes include the rate of change in early dialysis starts; rates of hospitalizations, deaths, and cost of predialysis care (wherever available); quarterly proportion of new starts; and acceptability of the knowledge translation materials. We randomized 55 multidisciplinary chronic disease clinics (clusters) in Canada to receive either an active knowledge translation intervention or no intervention for the uptake of the guideline on the timing of dialysis initiation. The active knowledge translation intervention consists of audit and feedback as well as patient- and provider-directed educational tools delivered at a comprehensive in-person medical detailing visit. Control clinics are only exposed to guideline

Evaluating Various Areas of Process Improvement in an Effort to Improve Clinical Research: Discussions from the 2012 Clinical Translational Science Award (CTSA) Clinical Research Management Workshop

PubMed Central

Cola, Philip A.; Rosenblum, Daniel

2013-01-01

Abstract Emphasis has been placed on assessing the efficiency of clinical and translational research as part of the National Institutes of Health (NIH) goal to “improve human health.” Improvements identified and implemented by individual organizations cannot address the research infrastructure needs of all clinical and translational research conducted. NIH's National Center for Advancing Translational Sciences (NCATS) has brought together 61 Clinical and Translational Science Award (CTSA) sites creating a virtual national laboratory that reflects the diversity and breadth of academic medical centers to collectively improve clinical and translational science. The annual Clinical Research Management workshop is organized by the CTSA consortium with participation from CTSA awardees, NIH, and others with an interest in clinical research management. The primary objective of the workshop is to disseminate information that improves clinical research management although the specific objectives of each workshop evolve within the consortium. The fifth annual workshop entitled “Learning by doing; applying evidence‐based tools to re‐engineer clinical research management” took place in June 2012. The primary objective of the 2012 workshop was to utilize data to evaluate, modify, and improve clinical research management. This report provides a brief summary of the workshop proceedings and the major themes discussed among the participants. PMID:23919369

Evaluating various areas of process improvement in an effort to improve clinical research: discussions from the 2012 Clinical Translational Science Award (CTSA) Clinical Research Management workshop.

PubMed

Strasser, Jane E; Cola, Philip A; Rosenblum, Daniel

2013-08-01

Emphasis has been placed on assessing the efficiency of clinical and translational research as part of the National Institutes of Health (NIH) goal to "improve human health." Improvements identified and implemented by individual organizations cannot address the research infrastructure needs of all clinical and translational research conducted. NIH's National Center for Advancing Translational Sciences (NCATS) has brought together 61 Clinical and Translational Science Award (CTSA) sites creating a virtual national laboratory that reflects the diversity and breadth of academic medical centers to collectively improve clinical and translational science. The annual Clinical Research Management workshop is organized by the CTSA consortium with participation from CTSA awardees, NIH, and others with an interest in clinical research management. The primary objective of the workshop is to disseminate information that improves clinical research management although the specific objectives of each workshop evolve within the consortium. The fifth annual workshop entitled "Learning by doing; applying evidence-based tools to re-engineer clinical research management" took place in June 2012. The primary objective of the 2012 workshop was to utilize data to evaluate, modify, and improve clinical research management. This report provides a brief summary of the workshop proceedings and the major themes discussed among the participants. © 2013 Wiley Periodicals, Inc.

Translating orthopaedic basic science into clinical relevance.

PubMed

Madry, Henning

2014-12-01

In orthopaedic and trauma surgery, the rapid evolution of biomedical research has fundamentally changed the perception of the musculoskeletal system. Here, the rigor of basic science and the art of musculoskeletal surgery have come together to create a new discipline -experimental orthopaedics- that holds great promise for the causative cure of many orthopaedic conditions. The Journal of Experimental Orthopaedics intends to bridge the gap between orthopaedic basic science and clinical relevance, to allow for a fruitful clinical translation of excellent and important investigations in the field of the entire musculoskeletal system.

CDISC SHARE, a Global, Cloud-based Resource of Machine-Readable CDISC Standards for Clinical and Translational Research

PubMed Central

Hume, Samuel; Chow, Anthony; Evans, Julie; Malfait, Frederik; Chason, Julie; Wold, J. Darcy; Kubick, Wayne; Becnel, Lauren B.

2018-01-01

The Clinical Data Interchange Standards Consortium (CDISC) is a global non-profit standards development organization that creates consensus-based standards for clinical and translational research. Several of these standards are now required by regulators for electronic submissions of regulated clinical trials’ data and by government funding agencies. These standards are free and open, available for download on the CDISC Website as PDFs. While these documents are human readable, they are not amenable to ready use by electronic systems. CDISC launched the CDISC Shared Health And Research Electronic library (SHARE) to provide the standards metadata in machine-readable formats to facilitate the automated management and implementation of the standards. This paper describes how CDISC SHARE’S standards can facilitate collecting, aggregating and analyzing standardized data from early design to end analysis; and its role as a central resource providing information systems with metadata that drives process automation including study setup and data pipelining. PMID:29888049

Clinical and translational scientist career success: metrics for evaluation.

PubMed

Lee, Linda S; Pusek, Susan N; McCormack, Wayne T; Helitzer, Deborah L; Martina, Camille A; Dozier, Ann M; Ahluwalia, Jasjit S; Schwartz, Lisa S; McManus, Linda M; Reynolds, Brian D; Haynes, Erin N; Rubio, Doris M

2012-10-01

Despite the increased emphasis on formal training in clinical and translational research and the growth in the number and scope of training programs over the past decade, the impact of training on research productivity and career success has yet to be fully evaluated at the institutional level. In this article, the Education Evaluation Working Group of the Clinical and Translational Science Award Consortium introduces selected metrics and methods associated with the assessment of key factors that affect research career success. The goals in providing this information are to encourage more consistent data collection across training sites, to foster more rigorous and systematic exploration of factors associated with career success, and to help address previously identified difficulties in program evaluation. © 2012 Wiley Periodicals, Inc.

D1-3: Marshfield Dictionary of Clinical and Translational Science (MD-CTS): An Online Reference for Clinical and Translational Science Terminology

PubMed Central

Finamore, Joe; Ray, William; Kadolph, Chris; Rastegar-Mojarad, Majid; Ye, Zhan; Jacqueline, Bohne; Tachinardi, Umberto; Mendonça, Eneida; Finnegan, Brian; Bartkowiak, Barbara; Weichelt, Bryan; Lin, Simon

2014-01-01

Background/Aims New terms are rapidly appearing in the literature and practice of clinical medicine and translational research. To catalog real-world usage of medical terms, we report the first construction of an online dictionary of clinical and translational medicinal terms, which are computationally generated in near real-time using a big data approach. This project is NIH CTSA-funded and developed by the Marshfield Clinic Research Foundation in conjunction with University of Wisconsin - Madison. Currently titled Marshfield Dictionary of Clinical and Translational Science (MD-CTS), this application is a Google-like word search tool. By entering a term into the search bar, MD-CTS will display that term’s definition, usage examples, contextual terms, related images, and ontological information. A prototype is available for public viewing at http://spellchecker.mfldclin.edu/. Methods We programmatically derived the lexicon for MD-CTS from scholarly communications by parsing through 15,156,745 MEDLINE abstracts and extracting all of the unique words found therein. We then ran this list through several filters in order to remove words that were not relevant for searching, such as common English words and numeric expressions. We then loaded the resulting 1,795,769 terms into SQL tables. Each term is cross-referenced with every occurrence in all abstracts in which it was found. Additional information is aggregated from Wiktionary, Bioportal, and Wikipedia in real-time and displayed on-screen. From this lexicon we created a supplemental dictionary resource (updated quarterly) to be used in Microsoft Office® products. Results We evaluated the utility of MD-CTS by creating a list of 100 words derived from recent clinical and translational medicine publications in the week of July 22, 2013. We then performed comparative searches for each term with Taber’s Cyclopedic Medical Dictionary, Stedman’s Medical Dictionary, Dorland’s Illustrated Medical Dictionary, Medical

Translational neuropathic pain research: A clinical perspective.

PubMed

Bouhassira, D; Attal, N

2016-12-03

Neuropathic pain encompasses a broad range of conditions associated with a lesion or disease of the peripheral or central somatosensory system and its prevalence in the general population may be as high as 7-8%. The interest in the pathophysiology of neuropathic pain has increased over the last two decades with an exponential increase in the number of experimental studies. However, despite the hopes raised by scientific discoveries, there has been no rational development of a truly new class of drugs. This situation revealing the limitations of certain experimental models, also results of limitations in clinical research. One of the reasons for the therapeutic difficulties in these patients is probably due to the fact that treatments are used in a uniform fashion whatever the clinical picture, while these syndromes are in fact highly heterogeneous. Clinical advances have recently been made in this field, following the validation of new specific clinical tools and the standardization of quantitative sensory testing paradigms facilitating improvements in the clinical characterization of these syndromes. It has been clearly demonstrated that neuropathic pain is a consistent clinical entity, but it is multidimensional in terms of its clinical expression, with different sensory profiles, potentially reflecting specific pathophysiological mechanisms. This new conceptualization of neuropathic pain should improve the characterization of the responder profiles in clinical trials and provide valuable information for the development of new and more clinically sound translational approaches in experimental models in animals. Copyright © 2016. Published by Elsevier Ltd.

Translating Alcohol Research

PubMed Central

Batman, Angela M.; Miles, Michael F.

2015-01-01

Alcohol use disorder (AUD) and its sequelae impose a major burden on the public health of the United States, and adequate long-term control of this disorder has not been achieved. Molecular and behavioral basic science research findings are providing the groundwork for understanding the mechanisms underlying AUD and have identified multiple candidate targets for ongoing clinical trials. However, the translation of basic research or clinical findings into improved therapeutic approaches for AUD must become more efficient. Translational research is a multistage process of streamlining the movement of basic biomedical research findings into clinical research and then to the clinical target populations. This process demands efficient bidirectional communication across basic, applied, and clinical science as well as with clinical practitioners. Ongoing work suggests rapid progress is being made with an evolving translational framework within the alcohol research field. This is helped by multiple interdisciplinary collaborative research structures that have been developed to advance translational work on AUD. Moreover, the integration of systems biology approaches with collaborative clinical studies may yield novel insights for future translational success. Finally, appreciation of genetic variation in pharmacological or behavioral treatment responses and optimal communication from bench to bedside and back may strengthen the success of translational research applications to AUD. PMID:26259085

Synthetic Biology and the Translational Imperative.

PubMed

Heidari Feidt, Raheleh; Ienca, Marcello; Elger, Bernice Simone; Folcher, Marc

2017-12-18

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."

Challenges facing translational research organizations in China: a qualitative multiple case study

PubMed Central

2013-01-01

Background Translational medicine is attracting much attention worldwide and many translational research organizations (TROs) have been established. In China, translational medicine has developed rapidly, but faces many challenges. This study was aimed at exploring these challenges faced by emerging TROs in China. Method A qualitative, multiple case study approach was used to assess the challenges faced by TROs in China. Data were collected between May and August 2012. Results Eight cases were identified. Overall, four themes that characterized TROs in China emerged from analyses: 1. objectives, organizer, and funding resources, 2. participating partners and research teams, 3. management, and 4. achievements. All TROs had objectives related to translating basic discovery to clinic treatment and cultivating translational researchers. In terms of organizer and funding resources, 7 out of 8 TROs were launched only by universities and/or hospitals, and funded mostly through research grants. As for participating partners and multidisciplinary research teams, all but one of the TROs only involved biomedical research institutions who were interested in translational research, and characterized as clinical research centers; 7 out of 8 TROs involved only researchers from biomedicine and clinical disciplines and none involved disciplines related to education, ethnicity, and sociology, or engaged the community. Current management of the TROs were generally nested within the traditional research management paradigms, and failed to adapt to the tenets of translational research. Half of the TROs were at developmental stages defined as infrastructure construction and recruitment of translational researchers. Conclusions TROs in China face the challenge of attracting sustainable funding sources, widening multidisciplinary cooperation, cultivating multi-disciplinary translational researchers and adapting current research management to translational research. Greater emphasis should

Knowledge Translation: Supports, Challenges, and Opportunities for Change in Early Intervention

ERIC Educational Resources Information Center

Rabinowicz, Susan; Ray, Sharon

2018-01-01

Knowledge translation (KT) provides a lens to examine the process of moving research-informed knowledge into early intervention practice (P. Sudsawad, 2007). The process of KT entails cognitive, affective, and behavioral stages that are mediated by factors intrinsic and extrinsic to the practitioner. Facilitators and barriers to this process may…

Clinical translation of controlled protein delivery systems for tissue engineering

PubMed Central

Spiller, Kara L.; Vunjak-Novakovic, Gordana

2013-01-01

Strategies that utilize controlled release of drugs and proteins for tissue engineering have enormous potential to regenerate damaged organs and tissues. The multiple advantages of controlled release strategies merit overcoming the significant challenges to translation, including high costs and long, difficult regulatory pathways. This review highlights the potential of controlled release of proteins for tissue engineering and regenerative medicine. We specifically discuss treatment modalities that have reached preclinical and clinical trials, with emphasis on controlled release systems for bone tissue engineering, the most advanced application with several products already in clinic. Possible strategies to address translational and regulatory concerns are also discussed. PMID:25787736

The Applicability of Lean and Six Sigma Techniques to Clinical and Translational Research

PubMed Central

Schweikhart, Sharon A.; Dembe, Allard E

2010-01-01

Background Lean and Six Sigma are business management strategies commonly used in production industries to improve process efficiency and quality. During the past decade, these process improvement techniques increasingly have been applied outside of the manufacturing sector, for example, in health care and in software development. This article concerns the potential use of Lean and Six Sigma to improve the processes involved in clinical and translational research. Improving quality, avoiding delays and errors, and speeding up the time to implementation of biomedical discoveries are prime objectives of the NIH Roadmap for Biomedical Research and the NIH Clinical and Translational Science Award (CTSA) program. Methods This article presents a description of the main principles, practices, and methodologies used in Lean and Six Sigma. Available literature involving applications of Lean and Six Sigma to health care, laboratory science, and clinical and translational research is reviewed. Specific issues concerning the use of these techniques in different phases of translational research are identified. Results Examples are provided of Lean and Six Sigma applications that are being planned at a current CTSA site, which could potentially be replicated elsewhere. We describe how different process improvement approaches are best adapted for particularly translational research phases. Conclusions Lean and Six Sigma process improvement methodologies are well suited to help achieve NIH’s goal of making clinical and translational research more efficient and cost-effective, enhancing the quality of the research, and facilitating the successful adoption of biomedical research findings into practice. PMID:19730130

Automated detection of diabetic retinopathy: barriers to translation into clinical practice.

PubMed

Abramoff, Michael D; Niemeijer, Meindert; Russell, Stephen R

2010-03-01

Automated identification of diabetic retinopathy (DR), the primary cause of blindness and visual loss for those aged 18-65 years, from color images of the retina has enormous potential to increase the quality, cost-effectiveness and accessibility of preventative care for people with diabetes. Through advanced image analysis techniques, retinal images are analyzed for abnormalities that define and correlate with the severity of DR. Translating automated DR detection into clinical practice will require surmounting scientific and nonscientific barriers. Scientific concerns, such as DR detection limits compared with human experts, can be studied and measured. Ethical, legal and political issues can be addressed, but are difficult or impossible to measure. The primary objective of this review is to survey the methods, potential benefits and limitations of automated detection in order to better manage translation into clinical practice, based on extensive experience with the systems we have developed.

Clinical and Translational Scientist Career Success: Metrics for Evaluation

PubMed Central

Lee, Linda S.; Pusek, Susan N.; McCormack, Wayne T.; Helitzer, Deborah L.; Martina, Camille A.; Dozier, Ann M.; Ahluwalia, Jasjit S.; Schwartz, Lisa S.; McManus, Linda M.; Reynolds, Brian D.; Haynes, Erin N.; Rubio, Doris M.

2012-01-01

Abstract Despite the increased emphasis on formal training in clinical and translational research and the growth in the number and scope of training programs over the past decade, the impact of training on research productivity and career success has yet to be fully evaluated at the institutional level. In this article, the Education Evaluation Working Group of the Clinical and Translational Science Award Consortium introduces selected metrics and methods associated with the assessment of key factors that affect research career success. The goals in providing this information are to encourage more consistent data collection across training sites, to foster more rigorous and systematic exploration of factors associated with career success, and to help address previously identified difficulties in program evaluation. Clin Trans Sci 2012; Volume 5: 400–407 PMID:23067352

NCI–RTOG Translational Program Strategic Guidelines for the Early-Stage Development of Radiosensitizers

PubMed Central

2013-01-01

The addition of chemotherapeutic agents to ionizing radiation has improved survival in many malignancies. Cure rates may be further improved by adding novel targeted agents to current radiotherapy or radiochemotherapy regimens. Despite promising laboratory data, progress in the clinical development of new drugs with radiation has been limited. To define and address the problems involved, a collaborative effort between individuals within the translational research program of the Radiation Oncology Therapy Group and the National Cancer Institute was established. We discerned challenges to drug development with radiation including: 1) the limited relevance of preclinical work, 2) the pharmaceutical industry’s diminished interest, and 3) the important individual skills and institutional commitments required to ensure a successful program. The differences between early-phase trial designs with and without radiation are noted as substantial. The traditional endpoints for early-phase clinical trials—acute toxicity and maximum-tolerated dose—are of limited value when combining targeted agents with radiation. Furthermore, response rate is not a useful surrogate marker of activity in radiation combination trials.Consequently, a risk-stratified model for drug-dose escalation with radiation is proposed, based upon the known and estimated adverse effects. The guidelines discuss new clinical trial designs, such as the time-to-event continual reassessment method design for phase I trials, randomized phase II “screening” trials, and the use of surrogate endpoints, such as pathological response. It is hoped that by providing a clear pathway, this article will accelerate the rate of drug development with radiation. PMID:23231975

Global regulation of mRNA translation and stability in the early Drosophila embryo by the Smaug RNA-binding protein.

PubMed

Chen, Linan; Dumelie, Jason G; Li, Xiao; Cheng, Matthew Hk; Yang, Zhiyong; Laver, John D; Siddiqui, Najeeb U; Westwood, J Timothy; Morris, Quaid; Lipshitz, Howard D; Smibert, Craig A

2014-01-07

Smaug is an RNA-binding protein that induces the degradation and represses the translation of mRNAs in the early Drosophila embryo. Smaug has two identified direct target mRNAs that it differentially regulates: nanos and Hsp83. Smaug represses the translation of nanos mRNA but has only a modest effect on its stability, whereas it destabilizes Hsp83 mRNA but has no detectable effect on Hsp83 translation. Smaug is required to destabilize more than one thousand mRNAs in the early embryo, but whether these transcripts represent direct targets of Smaug is unclear and the extent of Smaug-mediated translational repression is unknown. To gain a panoramic view of Smaug function in the early embryo, we identified mRNAs that are bound to Smaug using RNA co-immunoprecipitation followed by hybridization to DNA microarrays. We also identified mRNAs that are translationally repressed by Smaug using polysome gradients and microarrays. Comparison of the bound mRNAs to those that are translationally repressed by Smaug and those that require Smaug for their degradation suggests that a large fraction of Smaug's target mRNAs are both translationally repressed and degraded by Smaug. Smaug directly regulates components of the TRiC/CCT chaperonin, the proteasome regulatory particle and lipid droplets, as well as many metabolic enzymes, including several glycolytic enzymes. Smaug plays a direct and global role in regulating the translation and stability of a large fraction of the mRNAs in the early Drosophila embryo, and has unanticipated functions in control of protein folding and degradation, lipid droplet function and metabolism.

Pancreatic cancer: Translational research aspects and clinical implications

PubMed Central

Ansari, Daniel; Chen, Bi-Cheng; Dong, Lei; Zhou, Meng-Tao; Andersson, Roland

2012-01-01

Despite improvements in surgical techniques and adjuvant chemotherapy, the overall mortality rates in pancreatic cancer have generally remained relatively unchanged and the 5-year survival rate is actually below 2%. This paper will address the importance of achieving an early diagnosis and identifying markers for prognosis and response to therapy such as genes, proteins, microRNAs or epigenetic modifications. However, there are still major hurdles when translating investigational biomarkers into routine clinical practice. Furthermore, novel ways of secondary screening in high-risk individuals, such as artificial neural networks and modern imaging, will be discussed. Drug resistance is ubiquitous in pancreatic cancer. Several mechanisms of drug resistance have already been revealed, including human equilibrative nucleoside transporter-1 status, multidrug resistance proteins, aberrant signaling pathways, microRNAs, stromal influence, epithelial-mesenchymal transition-type cells and recently the presence of cancer stem cells/cancer-initiating cells. These factors must be considered when developing more customized types of intervention (“personalized medicine”). In the future, multifunctional nanoparticles that combine a specific targeting agent, an imaging probe, a cell-penetrating agent, a biocompatible polymer and an anti-cancer drug may become valuable for the management of patients with pancreatic cancer. PMID:22509073

Leading by Success: Impact of a Clinical & Translational Research Infrastructure Program to Address Health Inequities

PubMed Central

Shiramizu, Bruce; Shambaugh, Vicki; Petrovich, Helen; Seto, Todd B.; Ho, Tammy; Mokuau, Noreen; Hedges, Jerris R.

2016-01-01

Building research infrastructure capacity to address clinical and translational gaps has been a focus of funding agencies and foundations. Clinical and Translational Sciences Awards, Research Centers in Minority Institutions Infrastructure for Clinical and Translational Research (RCTR) and the Institutional Development Award Infrastructure for Clinical and Translational Research funded by United States (US) government to fund clinical translational research programs have existed for over a decade to address racial and ethnic health disparities across the US. While the impact on the nation’s health can’t be made in a short period, assessment of a program’s impact could be a litmus test to gauge its effectiveness at the institution and communities. We report the success of a Pilot Project Program in the University of Hawaii RCTR Award in advancing careers of emerging investigators and community collaborators. Our findings demonstrated that the investment has a far-reaching impact on engagement with community-based research collaborators, career advancement of health disparities investigators, and favorable impacts on health policy. PMID:27797013

Clinical translation and regulatory aspects of CAR/TCR-based adoptive cell therapies-the German Cancer Consortium approach.

PubMed

Krackhardt, Angela M; Anliker, Brigitte; Hildebrandt, Martin; Bachmann, Michael; Eichmüller, Stefan B; Nettelbeck, Dirk M; Renner, Matthias; Uharek, Lutz; Willimsky, Gerald; Schmitt, Michael; Wels, Winfried S; Schüssler-Lenz, Martina

2018-04-01

Adoptive transfer of T cells genetically modified by TCRs or CARs represents a highly attractive novel therapeutic strategy to treat malignant diseases. Various approaches for the development of such gene therapy medicinal products (GTMPs) have been initiated by scientists in recent years. To date, however, the number of clinical trials commenced in Germany and Europe is still low. Several hurdles may contribute to the delay in clinical translation of these therapeutic innovations including the significant complexity of manufacture and non-clinical testing of these novel medicinal products, the limited knowledge about the intricate regulatory requirements of the academic developers as well as limitations of funds for clinical testing. A suitable good manufacturing practice (GMP) environment is a key prerequisite and platform for the development, validation, and manufacture of such cell-based therapies, but may also represent a bottleneck for clinical translation. The German Cancer Consortium (DKTK) and the Paul-Ehrlich-Institut (PEI) have initiated joint efforts of researchers and regulators to facilitate and advance early phase, academia-driven clinical trials. Starting with a workshop held in 2016, stakeholders from academia and regulatory authorities in Germany have entered into continuing discussions on a diversity of scientific, manufacturing, and regulatory aspects, as well as the benefits and risks of clinical application of CAR/TCR-based cell therapies. This review summarizes the current state of discussions of this cooperative approach providing a basis for further policy-making and suitable modification of processes.

Metabolomics and Type 2 Diabetes: Translating Basic Research into Clinical Application.

PubMed

Klein, Matthias S; Shearer, Jane

2016-01-01

Type 2 diabetes (T2D) and its comorbidities have reached epidemic proportions, with more than half a billion cases expected by 2030. Metabolomics is a fairly new approach for studying metabolic changes connected to disease development and progression and for finding predictive biomarkers to enable early interventions, which are most effective against T2D and its comorbidities. In metabolomics, the abundance of a comprehensive set of small biomolecules (metabolites) is measured, thus giving insight into disease-related metabolic alterations. This review shall give an overview of basic metabolomics methods and will highlight current metabolomics research successes in the prediction and diagnosis of T2D. We summarized key metabolites changing in response to T2D. Despite large variations in predictive biomarkers, many studies have replicated elevated plasma levels of branched-chain amino acids and their derivatives, aromatic amino acids and α-hydroxybutyrate ahead of T2D manifestation. In contrast, glycine levels and lysophosphatidylcholine C18:2 are depressed in both predictive studies and with overt disease. The use of metabolomics for predicting T2D comorbidities is gaining momentum, as are our approaches for translating basic metabolomics research into clinical applications. As a result, metabolomics has the potential to enable informed decision-making in the realm of personalized medicine.

Metabolomics and Type 2 Diabetes: Translating Basic Research into Clinical Application

PubMed Central

Klein, Matthias S.; Shearer, Jane

2016-01-01

Type 2 diabetes (T2D) and its comorbidities have reached epidemic proportions, with more than half a billion cases expected by 2030. Metabolomics is a fairly new approach for studying metabolic changes connected to disease development and progression and for finding predictive biomarkers to enable early interventions, which are most effective against T2D and its comorbidities. In metabolomics, the abundance of a comprehensive set of small biomolecules (metabolites) is measured, thus giving insight into disease-related metabolic alterations. This review shall give an overview of basic metabolomics methods and will highlight current metabolomics research successes in the prediction and diagnosis of T2D. We summarized key metabolites changing in response to T2D. Despite large variations in predictive biomarkers, many studies have replicated elevated plasma levels of branched-chain amino acids and their derivatives, aromatic amino acids and α-hydroxybutyrate ahead of T2D manifestation. In contrast, glycine levels and lysophosphatidylcholine C18:2 are depressed in both predictive studies and with overt disease. The use of metabolomics for predicting T2D comorbidities is gaining momentum, as are our approaches for translating basic metabolomics research into clinical applications. As a result, metabolomics has the potential to enable informed decision-making in the realm of personalized medicine. PMID:26636104

Clinical guideline for nurse-led early extubation after coronary artery bypass: an evaluation.

PubMed

Hawkes, Claire; Foxcroft, David R; Yerrell, Paul

2010-09-01

This paper is a report of an investigation of the development, implementation and outcomes of a clinical guideline for nurse-led early extubation of adult coronary artery bypass graft patients. Healthcare knowledge translation and utilization is an emerging but under-developed research area. The complex context for guideline development and use is methodologically challenging for robust and rigorous evaluation. This study contributes one such evaluation. This was a mixed methods evaluation, with a dominant quantitative study with a secondary qualitative study in a single UK cardiac surgery centre. An interrupted time series study (N = 567 elective coronary artery bypass graft patients) with concurrent within person controls was used to measure the impact of the guideline on the primary outcome: time to extubation. Semi-structured interviews with 11 clinical staff, informed by applied practitioner ethnography, explored the process of guideline development and implementation. The data were collected between January 2001 and January 2003. There was no change in the interrupted time series study primary outcome as a consequence of the guideline implementation. The qualitative study identified three themes: context, process and tensions highlighting that the guideline did not require clinicians to change their practice, although it may have helped maintain practice through its educative role. Further investigation and development of appropriate methods to capture the dynamism in healthcare contexts and its impact on guideline implementation seems warranted. Multi-site mixed methods investigations and programmes of research exploring knowledge translation and utilization initiatives, such as guideline implementation, are needed.

Illustrating idiographic methods for translation research: moderation effects, natural clinical experiments, and complex treatment-by-subgroup interactions.

PubMed

Ridenour, Ty A; Wittenborn, Andrea K; Raiff, Bethany R; Benedict, Neal; Kane-Gill, Sandra

2016-03-01

A critical juncture in translation research involves the preliminary studies of intervention tools, provider training programs, policies, and other mechanisms used to leverage knowledge garnered at one translation stage into another stage. Potentially useful for such studies are rigorous techniques for conducting within-subject clinical trials, which have advanced incrementally over the last decade. However, these methods have largely not been utilized within prevention or translation contexts. The purpose of this manuscript is to demonstrate the flexibility, wide applicability, and rigor of idiographic clinical trials for preliminary testing of intervention mechanisms. Specifically demonstrated are novel uses of state-space modeling for testing intervention mechanisms of short-term outcomes, identifying heterogeneity in and moderation of within-person treatment mechanisms, a horizontal line plot to refine sampling design during the course of a clinic-based experimental study, and the need to test a treatment's efficacy as treatment is administered along with (e.g., traditional 12-month outcomes).

Implementing 'translational' biomedical research: convergence and divergence among clinical and basic scientists.

PubMed

Morgan, Myfanwy; Barry, Christine A; Donovan, Jenny L; Sandall, Jane; Wolfe, Charles D A; Boaz, Annette

2011-10-01

Universities are increasingly regarded as key actors in the new 'knowledge economy', with requirements to produce market-oriented knowledge and engage in commercialization. This is of particular significance in the biomedical field, reflecting the perceived gap between success in terms of scientific discoveries and its transformation into products. The dominant discourse attributes this situation to 'blocks' in the translational pathway from 'bench to bedside', leading to policies to 'reengineer' the research enterprise. This study examines a pilot initiative established by the UK's Medical Research Council (MRC). This involved employing a change agent (Research Translator) supported by a small amount of translational funding to promote the culture and practice of translational research at a university/hospital site in England. An ethnographically informed case study involving semi-structured and open exploratory interviews, observation and document review, was conducted in 2008. Analysis and interpretation were informed by Bourdieu's logic of practice applied to science. The requirements of translational research promoted by the Research Translator and its sources of capital (authority, prestige etc) were largely congruent with the 'field' of clinical science. In contrast, translational research diverged from perceptions of 'legitimate' science and requirements for capital accumulation held by the majority of basic scientists who often described this research as 'high risk' and were resistant to the Research Translator's advice. However some differences in motivations and practices were identified within groups of scientists associated with career stage, work environment and specialty. We argue that there are convergent and divergent forces that influence scientists' readiness to adopt a market-oriented translational research model and in turn facilitate or constrain the effectiveness of a knowledge broker. We also identify ways in which current structures and

Team building: electronic management-clinical translational research (eM-CTR) systems.

PubMed

Cecchetti, Alfred A; Parmanto, Bambang; Vecchio, Marcella L; Ahmad, Sjarif; Buch, Shama; Zgheib, Nathalie K; Groark, Stephen J; Vemuganti, Anupama; Romkes, Marjorie; Sciurba, Frank; Donahoe, Michael P; Branch, Robert A

2009-12-01

Classical drug exposure: response studies in clinical pharmacology represent the quintessential prototype for Bench to Bedside-Clinical Translational Research. A fundamental premise of this approach is for a multidisciplinary team of researchers to design and execute complex, in-depth mechanistic studies conducted in relatively small groups of subjects. The infrastructure support for this genre of clinical research is not well-handled by scaling down of infrastructure used for large Phase III clinical trials. We describe a novel, integrated strategy, whose focus is to support and manage a study using an Information Hub, Communication Hub, and Data Hub design. This design is illustrated by an application to a series of varied projects sponsored by Special Clinical Centers of Research in chronic obstructive pulmonary disease at the University of Pittsburgh. In contrast to classical informatics support, it is readily scalable to large studies. Our experience suggests the culture consequences of research group self-empowerment is not only economically efficient but transformative to the research process.

Design control for clinical translation of 3D printed modular scaffolds.

PubMed

Hollister, Scott J; Flanagan, Colleen L; Zopf, David A; Morrison, Robert J; Nasser, Hassan; Patel, Janki J; Ebramzadeh, Edward; Sangiorgio, Sophia N; Wheeler, Matthew B; Green, Glenn E

2015-03-01

The primary thrust of tissue engineering is the clinical translation of scaffolds and/or biologics to reconstruct tissue defects. Despite this thrust, clinical translation of tissue engineering therapies from academic research has been minimal in the 27 year history of tissue engineering. Academic research by its nature focuses on, and rewards, initial discovery of new phenomena and technologies in the basic research model, with a view towards generality. Translation, however, by its nature must be directed at specific clinical targets, also denoted as indications, with associated regulatory requirements. These regulatory requirements, especially design control, require that the clinical indication be precisely defined a priori, unlike most academic basic tissue engineering research where the research target is typically open-ended, and furthermore requires that the tissue engineering therapy be constructed according to design inputs that ensure it treats or mitigates the clinical indication. Finally, regulatory approval dictates that the constructed system be verified, i.e., proven that it meets the design inputs, and validated, i.e., that by meeting the design inputs the therapy will address the clinical indication. Satisfying design control requires (1) a system of integrated technologies (scaffolds, materials, biologics), ideally based on a fundamental platform, as compared to focus on a single technology, (2) testing of design hypotheses to validate system performance as opposed to mechanistic hypotheses of natural phenomena, and (3) sequential testing using in vitro, in vivo, large preclinical and eventually clinical tests against competing therapies, as compared to single experiments to test new technologies or test mechanistic hypotheses. Our goal in this paper is to illustrate how design control may be implemented in academic translation of scaffold based tissue engineering therapies. Specifically, we propose to (1) demonstrate a modular platform approach

Design Control for Clinical Translation of 3D Printed Modular Scaffolds

PubMed Central

Hollister, Scott J.; Flanagan, Colleen L.; Zopf, David A.; Morrison, Robert J.; Nasser, Hassan; Patel, Janki J.; Ebramzadeh, Edward; Sangiorgio, Sophia N.; Wheeler, Matthew B.; Green, Glenn E.

2015-01-01

The primary thrust of tissue engineering is the clinical translation of scaffolds and/or biologics to reconstruct tissue defects. Despite this thrust, clinical translation of tissue engineering therapies from academic research has been minimal in the 27 year history of tissue engineering. Academic research by its nature focuses on, and rewards, initial discovery of new phenomena and technologies in the basic research model, with a view towards generality. Translation, however, by its nature must be directed at specific clinical targets, also denoted as indications, with associated regulatory requirements. These regulatory requirements, especially design control, require that the clinical indication be precisely defined a priori, unlike most academic basic tissue engineering research where the research target is typically open-ended, and furthermore requires that the tissue engineering therapy be constructed according to design inputs that ensure it treats or mitigates the clinical indication. Finally, regulatory approval dictates that the constructed system be verified, i.e., proven that it meets the design inputs, and validated, i.e., that by meeting the design inputs the therapy will address the clinical indication. Satisfying design control requires (1) a system of integrated technologies (scaffolds, materials, biologics), ideally based on a fundamental platform, as compared to focus on a single technology, (2) testing of design hypotheses to validate system performance as opposed to mechanistic hypotheses of natural phenomena, and (3) sequential testing using in vitro, in vivo, large preclinical and eventually clinical tests against competing therapies, as compared to single experiments to test new technologies or test mechanistic hypotheses. Our goal in this paper is to illustrate how design control may be implemented in academic translation of scaffold based tissue engineering therapies. Specifically, we propose to (1) demonstrate a modular platform approach

Global regulation of mRNA translation and stability in the early Drosophila embryo by the Smaug RNA-binding protein

PubMed Central

2014-01-01

Background Smaug is an RNA-binding protein that induces the degradation and represses the translation of mRNAs in the early Drosophila embryo. Smaug has two identified direct target mRNAs that it differentially regulates: nanos and Hsp83. Smaug represses the translation of nanos mRNA but has only a modest effect on its stability, whereas it destabilizes Hsp83 mRNA but has no detectable effect on Hsp83 translation. Smaug is required to destabilize more than one thousand mRNAs in the early embryo, but whether these transcripts represent direct targets of Smaug is unclear and the extent of Smaug-mediated translational repression is unknown. Results To gain a panoramic view of Smaug function in the early embryo, we identified mRNAs that are bound to Smaug using RNA co-immunoprecipitation followed by hybridization to DNA microarrays. We also identified mRNAs that are translationally repressed by Smaug using polysome gradients and microarrays. Comparison of the bound mRNAs to those that are translationally repressed by Smaug and those that require Smaug for their degradation suggests that a large fraction of Smaug’s target mRNAs are both translationally repressed and degraded by Smaug. Smaug directly regulates components of the TRiC/CCT chaperonin, the proteasome regulatory particle and lipid droplets, as well as many metabolic enzymes, including several glycolytic enzymes. Conclusions Smaug plays a direct and global role in regulating the translation and stability of a large fraction of the mRNAs in the early Drosophila embryo, and has unanticipated functions in control of protein folding and degradation, lipid droplet function and metabolism. PMID:24393533

Coherent anti-Stokes Raman scattering microscopy: overcoming technical barriers for clinical translation

PubMed Central

Tu, Haohua; Boppart, Stephen A.

2015-01-01

Clinical translation of coherent anti-Stokes Raman scattering microscopy is of great interest because of the advantages of noninvasive label-free imaging, high sensitivity, and chemical specificity. For this to happen, we have identified and review the technical barriers that must be overcome. Prior investigations have developed advanced techniques (features), each of which can be used to effectively overcome one particular technical barrier. However, the implementation of one or a small number of these advanced features in previous attempts for clinical translation has often introduced more tradeoffs than benefits. In this review, we outline a strategy that would integrate multiple advanced features to overcome all the technical barriers simultaneously, effectively reduce tradeoffs, and synergistically optimize CARS microscopy for clinical translation. The operation of the envisioned system incorporates coherent Raman micro-spectroscopy for identifying vibrational biomolecular markers of disease and single-frequency (or hyperspectral) Raman imaging of these specific biomarkers for real-time in vivo diagnostics and monitoring. An optimal scheme of clinical CARS micro-spectroscopy for thin ex vivo tissues. PMID:23674234

Training and career development in clinical and translational science: an opportunity for rehabilitation scientists.

PubMed

Kelly, Thomas H; Mattacola, Carl G

2010-11-01

The National Institutes of Health's Clinical and Translational Science Award initiative is designed to establish and promote academic centers of clinical and translational science (CTS) that are empowered to train and advance multi- and interdisciplinary investigators and research teams to apply new scientific knowledge and techniques to enhance patient care. Among the key components of a full-service center for CTS is an educational platform to support research training in CTS. Educational objectives and resources available to support the career development of the clinical and translational scientists, including clinical research education, mentored research training, and career development support, are described. The purpose of the article is to provide an overview of the CTS educational model so that rehabilitation specialists can become more aware of potential resources that are available and become more involved in the delivery and initiation of the CTS model in their own workplace. Rehabilitation clinicians and scientists are well positioned to play important leadership roles in advancing the academic mission of CTS. Rigorous academic training in rehabilitation science serves as an effective foundation for supporting the translation of basic scientific discovery into improved health care. Rehabilitation professionals are immersed in patient care, familiar with interdisciplinary health care delivery, and skilled at working with multiple health care professionals. The NIH Clinical and Translational Science Award initiative is an excellent opportunity to advance the academic development of rehabilitation scientists.

Academic Perspectives and Experiences of Knowledge Translation: A Qualitative Study of Public Health Researchers

ERIC Educational Resources Information Center

Collie, Alex; Zardo, Pauline; McKenzie, Donna Margaret; Ellis, Niki

2016-01-01

This study explores the views and experiences of knowledge translation of 14 Australian public health academics. Capacity to engage in knowledge translation is influenced by factors within the academic context and the interaction of the academic and policy environments. Early and mid-career researchers reported a different set of experiences and…

Low clinical diagnostic accuracy of early vs advanced Parkinson disease: clinicopathologic study.

PubMed

Adler, Charles H; Beach, Thomas G; Hentz, Joseph G; Shill, Holly A; Caviness, John N; Driver-Dunckley, Erika; Sabbagh, Marwan N; Sue, Lucia I; Jacobson, Sandra A; Belden, Christine M; Dugger, Brittany N

2014-07-29

Determine diagnostic accuracy of a clinical diagnosis of Parkinson disease (PD) using neuropathologic diagnosis as the gold standard. Data from the Arizona Study of Aging and Neurodegenerative Disorders were used to determine the predictive value of a clinical PD diagnosis, using 2 clinical diagnostic confidence levels, PossPD (never treated or not clearly responsive) and ProbPD (responsive to medications). Neuropathologic diagnosis was the gold standard. Based on first visit, 9 of 34 (26%) PossPD cases had neuropathologically confirmed PD while 80 of 97 (82%) ProbPD cases had confirmed PD. PD was confirmed in 8 of 15 (53%) ProbPD cases with <5 years of disease duration and 72 of 82 (88%) with ≥5 years of disease duration. Using final diagnosis at time of death, 91 of 107 (85%) ProbPD cases had confirmed PD. Clinical variables that improved diagnostic accuracy were medication response, motor fluctuations, dyskinesias, and hyposmia. Using neuropathologic findings of PD as the gold standard, this study establishes the novel findings of only 26% accuracy for a clinical diagnosis of PD in untreated or not clearly responsive subjects, 53% accuracy in early PD responsive to medication (<5 years' duration), and >85% diagnostic accuracy of longer duration, medication-responsive PD. Caution is needed when interpreting clinical studies of PD, especially studies of early disease that do not have autopsy confirmation. The need for a tissue or other diagnostic biomarker is reinforced. This study provides Class II evidence that a clinical diagnosis of PD identifies patients who will have pathologically confirmed PD with a sensitivity of 88% and specificity of 68%. © 2014 American Academy of Neurology.

Early-Life Nutrition and Neurodevelopment: Use of the Piglet as a Translational Model12

PubMed Central

Mudd, Austin T

2017-01-01

Optimal nutrition early in life is critical to ensure proper structural and functional development of infant organ systems. Although pediatric nutrition historically has emphasized research on the relation between nutrition, growth rates, and gastrointestinal maturation, efforts increasingly have focused on how nutrition influences neurodevelopment. The provision of human milk is considered the gold standard in pediatric nutrition; thus, there is interest in understanding how functional nutrients and bioactive components in milk may modulate developmental processes. The piglet has emerged as an important translational model for studying neurodevelopmental outcomes influenced by pediatric nutrition. Given the comparable nutritional requirements and strikingly similar brain developmental patterns between young pigs and humans, the piglet is being used increasingly in developmental nutritional neuroscience studies. The piglet primarily has been used to assess the effects of dietary fatty acids and their accretion in the brain throughout neurodevelopment. However, recent research indicates that other dietary components, including choline, iron, cholesterol, gangliosides, and sialic acid, among other compounds, also affect neurodevelopment in the pig model. Moreover, novel analytical techniques, including but not limited to MRI, behavioral assessments, and molecular quantification, allow for a more holistic understanding of how nutrition affects neurodevelopmental patterns. By combining early-life nutritional interventions with innovative analytical approaches, opportunities abound to quantify factors affecting neurodevelopmental trajectories in the neonate. This review discusses research using the translational pig model with primary emphasis on early-life nutrition interventions assessing neurodevelopment outcomes, while also discussing nutritionally-sensitive methods to characterize brain maturation. PMID:28096130

Clinical and Translational Science Awards: can they increase the efficiency and speed of clinical and translational research?

PubMed

Heller, Caren; de Melo-Martín, Inmaculada

2009-04-01

Most agree that the recent decades-long boom in biomedical research discoveries has not had a sufficient effect on the public's health. To overcome some of the barriers to speeding clinical and translational (C/T) research, the National Institutes of Health has established the Institutional Clinical and Translational Science Award (CTSA). To explore whether the CTSA proposal addresses major C/T barriers and whether funded institutions offer adequate solutions, the authors reviewed the obstacles to C/T research described in the literature and examined the completeness of the solutions offered by the 12 initial CTSA awardees. Through an analysis of the literature, the authors categorized C/T barriers into three categories (research workforce, research operations, and organizational silos). They then analyzed each CTSA proposal regarding the types of programs offered to address these barriers. They found that, in general, institutions developed detailed programs to address research workforce and research operations barriers but had limited to no solutions for organizational silos. The authors suggest that differences in how barriers are addressed are consistent with the degree of control that CTSA centers have over these obstacles and solutions. They argue that although CTSA centers might have an important role in successfully addressing some of the barriers to C/T research, CTSA centers might ultimately have difficulties achieving their purported goal of facilitating and increasing the efficiency and speed of C/T research because of a lack of control over solutions to some important obstacles facing such research.

Classifying publications from the clinical and translational science award program along the translational research spectrum: a machine learning approach.

PubMed

Surkis, Alisa; Hogle, Janice A; DiazGranados, Deborah; Hunt, Joe D; Mazmanian, Paul E; Connors, Emily; Westaby, Kate; Whipple, Elizabeth C; Adamus, Trisha; Mueller, Meridith; Aphinyanaphongs, Yindalon

2016-08-05

Translational research is a key area of focus of the National Institutes of Health (NIH), as demonstrated by the substantial investment in the Clinical and Translational Science Award (CTSA) program. The goal of the CTSA program is to accelerate the translation of discoveries from the bench to the bedside and into communities. Different classification systems have been used to capture the spectrum of basic to clinical to population health research, with substantial differences in the number of categories and their definitions. Evaluation of the effectiveness of the CTSA program and of translational research in general is hampered by the lack of rigor in these definitions and their application. This study adds rigor to the classification process by creating a checklist to evaluate publications across the translational spectrum and operationalizes these classifications by building machine learning-based text classifiers to categorize these publications. Based on collaboratively developed definitions, we created a detailed checklist for categories along the translational spectrum from T0 to T4. We applied the checklist to CTSA-linked publications to construct a set of coded publications for use in training machine learning-based text classifiers to classify publications within these categories. The training sets combined T1/T2 and T3/T4 categories due to low frequency of these publication types compared to the frequency of T0 publications. We then compared classifier performance across different algorithms and feature sets and applied the classifiers to all publications in PubMed indexed to CTSA grants. To validate the algorithm, we manually classified the articles with the top 100 scores from each classifier. The definitions and checklist facilitated classification and resulted in good inter-rater reliability for coding publications for the training set. Very good performance was achieved for the classifiers as represented by the area under the receiver operating

Software for MR image overlay guided needle insertions: the clinical translation process

NASA Astrophysics Data System (ADS)

Ungi, Tamas; U-Thainual, Paweena; Fritz, Jan; Iordachita, Iulian I.; Flammang, Aaron J.; Carrino, John A.; Fichtinger, Gabor

2013-03-01

PURPOSE: Needle guidance software using augmented reality image overlay was translated from the experimental phase to support preclinical and clinical studies. Major functional and structural changes were needed to meet clinical requirements. We present the process applied to fulfill these requirements, and selected features that may be applied in the translational phase of other image-guided surgical navigation systems. METHODS: We used an agile software development process for rapid adaptation to unforeseen clinical requests. The process is based on iterations of operating room test sessions, feedback discussions, and software development sprints. The open-source application framework of 3D Slicer and the NA-MIC kit provided sufficient flexibility and stable software foundations for this work. RESULTS: All requirements were addressed in a process with 19 operating room test iterations. Most features developed in this phase were related to workflow simplification and operator feedback. CONCLUSION: Efficient and affordable modifications were facilitated by an open source application framework and frequent clinical feedback sessions. Results of cadaver experiments show that software requirements were successfully solved after a limited number of operating room tests.

Molecular Dimensions of Gastric Cancer: Translational and Clinical Perspectives.

PubMed

Choi, Yoon Young; Noh, Sung Hoon; Cheong, Jae-Ho

2016-01-01

Gastric cancer is a global health burden and has the highest incidence in East Asia. This disease is complex in nature because it arises from multiple interactions of genetic, local environmental, and host factors, resulting in biological heterogeneity. This genetic intricacy converges on molecular characteristics reflecting the pathophysiology, tumor biology, and clinical outcome. Therefore, understanding the molecular characteristics at a genomic level is pivotal to improving the clinical care of patients with gastric cancer. A recent landmark study, The Cancer Genome Atlas (TCGA) project, showed the molecular landscape of gastric cancer through a comprehensive molecular evaluation of 295 primary gastric cancers. The proposed molecular classification divided gastric cancer into four subtypes: Epstein-Barr virus-positive, microsatellite unstable, genomic stable, and chromosomal instability. This information will be taken into account in future clinical trials and will be translated into clinical therapeutic decisions. To fully realize the clinical benefit, many challenges must be overcome. Rapid growth of high-throughput biology and functional validation of molecular targets will further deepen our knowledge of molecular dimensions of this cancer, allowing for personalized precision medicine.

Foundational biomedical informatics research in the clinical and translational science era: a call to action.

PubMed

Payne, Philip R O; Embi, Peter J; Niland, Joyce

2010-01-01

Advances in clinical and translational science, along with related national-scale policy and funding mechanisms, have provided significant opportunities for the advancement of applied clinical research informatics (CRI) and translational bioinformatics (TBI). Such efforts are primarily oriented to application and infrastructure development and are critical to the conduct of clinical and translational research. However, they often come at the expense of the foundational CRI and TBI research needed to grow these important biomedical informatics subdisciplines and ensure future innovations. In light of this challenge, it is critical that a number of steps be taken, including the conduct of targeted advocacy campaigns, the development of community-accepted research agendas, and the continued creation of forums for collaboration and knowledge exchange. Such efforts are needed to ensure that the biomedical informatics community is able to advance CRI and TBI science in the context of the modern clinical and translational science era.

Applying Process Improvement Methods to Clinical and Translational Research: Conceptual Framework and Case Examples.

PubMed

Daudelin, Denise H; Selker, Harry P; Leslie, Laurel K

2015-12-01

There is growing appreciation that process improvement holds promise for improving quality and efficiency across the translational research continuum but frameworks for such programs are not often described. The purpose of this paper is to present a framework and case examples of a Research Process Improvement Program implemented at Tufts CTSI. To promote research process improvement, we developed online training seminars, workshops, and in-person consultation models to describe core process improvement principles and methods, demonstrate the use of improvement tools, and illustrate the application of these methods in case examples. We implemented these methods, as well as relational coordination theory, with junior researchers, pilot funding awardees, our CTRC, and CTSI resource and service providers. The program focuses on capacity building to address common process problems and quality gaps that threaten the efficient, timely and successful completion of clinical and translational studies. © 2015 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc.

Medical students' attitudes towards early clinical exposure in Iran.

PubMed

Khabaz Mafinejad, Mahboobeh; Mirzazadeh, Azim; Peiman, Soheil; Khajavirad, Nasim; Mirabdolhagh Hazaveh, Mojgan; Edalatifard, Maryam; Allameh, Seyed-Farshad; Naderi, Neda; Foroumandi, Morteza; Afshari, Ali; Asghari, Fariba

2016-06-19

This study was carried out to investigate the medical students' attitudes towards early clinical exposure at Tehran University of Medical Sciences. A cross-sectional study was conducted during 2012-2015. A convenience sample of 298 first- and second-year students, enrolled in the undergraduate medical curriculum, participated in an early clinical exposure program. To collect data from medical students, a questionnaire consisting of open-ended questions and structured questions, rated on a five-point Likert scale, was used to investigate students' attitudes toward early clinical exposure. Of the 298 medical students, 216 (72%) completed the questionnaires. The results demonstrated that medical students had a positive attitude toward early clinical exposure. Most students (80.1%) stated that early clinical exposure could familiarize them with the role of basic sciences knowledge in medicine and how to apply this knowledge in clinical settings. Moreover, 84.5% of them believed that early clinical exposure increased their interest in medicine and encouraged them to read more. Furthermore, content analysis of the students' responses uncovered three main themes of early clinical exposure, were considered helpful to improve learning: "integration of theory and practice", "interaction with others and professional development" and "desire and motivation for learning medicine". Medical students found their first experience with clinical setting valuable. Providing clinical exposure in the initial years of medical curricula and teaching the application of basic sciences knowledge in clinical practice can enhance students' understanding of the role they will play in the future as a physician.

The Quantitative Evaluation of the Clinical and Translational Science Awards (CTSA) Program Based on Science Mapping and Scientometric Analysis

PubMed Central

Zhang, Yin; Wang, Lei

2013-01-01

Abstract The Clinical and Translational Science Awards (CTSA) program is one of the most important initiatives in translational medical funding. The quantitative evaluation of the efficiency and performance of the CTSA program has a significant referential meaning for the decision making of global translational medical funding. Using science mapping and scientometric analytic tools, this study quantitatively analyzed the scientific articles funded by the CTSA program. The results of the study showed that the quantitative productivities of the CTSA program had a stable increase since 2008. In addition, the emerging trends of the research funded by the CTSA program covered clinical and basic medical research fields. The academic benefits from the CTSA program were assisting its members to build a robust academic home for the Clinical and Translational Science and to attract other financial support. This study provided a quantitative evaluation of the CTSA program based on science mapping and scientometric analysis. Further research is required to compare and optimize other quantitative methods and to integrate various research results. PMID:24330689

The quantitative evaluation of the Clinical and Translational Science Awards (CTSA) program based on science mapping and scientometric analysis.

PubMed

Zhang, Yin; Wang, Lei; Diao, Tianxi

2013-12-01

The Clinical and Translational Science Awards (CTSA) program is one of the most important initiatives in translational medical funding. The quantitative evaluation of the efficiency and performance of the CTSA program has a significant referential meaning for the decision making of global translational medical funding. Using science mapping and scientometric analytic tools, this study quantitatively analyzed the scientific articles funded by the CTSA program. The results of the study showed that the quantitative productivities of the CTSA program had a stable increase since 2008. In addition, the emerging trends of the research funded by the CTSA program covered clinical and basic medical research fields. The academic benefits from the CTSA program were assisting its members to build a robust academic home for the Clinical and Translational Science and to attract other financial support. This study provided a quantitative evaluation of the CTSA program based on science mapping and scientometric analysis. Further research is required to compare and optimize other quantitative methods and to integrate various research results. © 2013 Wiley Periodicals, Inc.

Improving clinical and translational research training: a qualitative evaluation of the Atlanta Clinical and Translational Science Institute KL2-mentored research scholars program

PubMed Central

Comeau, Dawn L; Escoffery, Cam; Freedman, Ariela; Ziegler, Thomas R; Blumberg, Henry M

2017-01-01

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. PMID:27591319

[The Contribution of GMP-grade Hospital Preparation to Translational Research].

PubMed

Yonezawa, Atsushi; Kajiwara, Moto; Minami, Ikuko; Omura, Tomohiro; Nakagawa, Shunsaku; Matsubara, Kazuo

2015-01-01

Translational research is important for applying the outcomes of basic research studies to practical medical treatments. In exploratory early-phase clinical trials for an innovative therapy, researchers should generally manufacture investigational agents by themselves. To provide investigational agents with safety and high quality in clinical studies, appropriate production management and quality control are essential. In the Department of Pharmacy of Kyoto University Hospital, a manufacturing facility for sterile drugs was established, independent of existing manufacturing facilities. Manuals on production management and quality control were developed according to Good Manufacturing Practices (GMP) for Investigational New Drugs (INDs). Advanced clinical research has been carried out using investigational agents manufactured in our facility. These achievements contribute to both the safety of patients and the reliability of clinical studies. In addition, we are able to do licensing-out of our technique for the manufacture of investigational drugs. In this symposium, we will introduce our GMP grade manufacturing facility for sterile drugs and discuss the role of GMP grade hospital preparation in translational research.

Bedside to Bench: Integrating Quantitative Clinical Pharmacology and Reverse Translation to Optimize Drug Development.

PubMed

Gibbs, John P; Menon, Rajeev; Kasichayanula, Sreeneeranj

2018-02-01

With so much emphasis on reducing attrition and becoming more efficient in the delivery of healthcare, there are many opportunities to leverage existing clinical data in drug development and to foster the practice of reverse translation. The application of quantitative approaches to convert clinical trial and real-world data to knowledge will continue to drive innovation. Herein we discuss recent examples of reverse translation and consider future opportunities to capture critical clinical knowledge to inform decision-making in drug development. © 2017 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Debugging Nano-Bio Interfaces: Systematic Strategies to Accelerate Clinical Translation of Nanotechnologies.

PubMed

Mahmoudi, Morteza

2018-03-17

Despite considerable efforts in the field of nanomedicine that have been made by researchers, funding agencies, entrepreneurs, and the media, fewer nanoparticle (NP) technologies than expected have made it to clinical trials. The wide gap between the efforts and effective clinical translation is, at least in part, due to multiple overlooked factors in both in vitro and in vivo environments, a poor understanding of the nano-bio interface, and misinterpretation of the data collected in vitro, all of which reduce the accuracy of predictions regarding the NPs' fate and safety in humans. To minimize this bench-to-clinic gap, which may accelerate successful clinical translation of NPs, this opinion paper aims to introduce strategies for systematic debugging of nano-bio interfaces in the current literature. Copyright © 2018 Elsevier Ltd. All rights reserved.

Non-clinical studies in the process of new drug development - Part II: Good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies.

PubMed

Andrade, E L; Bento, A F; Cavalli, J; Oliveira, S K; Schwanke, R C; Siqueira, J M; Freitas, C S; Marcon, R; Calixto, J B

2016-12-12

The process of drug development involves non-clinical and clinical studies. Non-clinical studies are conducted using different protocols including animal studies, which mostly follow the Good Laboratory Practice (GLP) regulations. During the early pre-clinical development process, also known as Go/No-Go decision, a drug candidate needs to pass through several steps, such as determination of drug availability (studies on pharmacokinetics), absorption, distribution, metabolism and elimination (ADME) and preliminary studies that aim to investigate the candidate safety including genotoxicity, mutagenicity, safety pharmacology and general toxicology. These preliminary studies generally do not need to comply with GLP regulations. These studies aim at investigating the drug safety to obtain the first information about its tolerability in different systems that are relevant for further decisions. There are, however, other studies that should be performed according to GLP standards and are mandatory for the safe exposure to humans, such as repeated dose toxicity, genotoxicity and safety pharmacology. These studies must be conducted before the Investigational New Drug (IND) application. The package of non-clinical studies should cover all information needed for the safe transposition of drugs from animals to humans, generally based on the non-observed adverse effect level (NOAEL) obtained from general toxicity studies. After IND approval, other GLP experiments for the evaluation of chronic toxicity, reproductive and developmental toxicity, carcinogenicity and genotoxicity, are carried out during the clinical phase of development. However, the necessity of performing such studies depends on the new drug clinical application purpose.

Views of Translational Research from a Somewhat Translational Scientist

PubMed Central

Talman, William T.

2013-01-01

This review arose from a talk entitled “Identifying Targets” and given by the author at EB2011 at the invitation of the American Federation for Medical Research (AFMR). The presentation was part of the AFMR workshop entitled “Keys for Translation: Science and Strategy” and focused on identifying clinically relevant targets as a result of observations made during basic scientific studies. The review emphasizes that targets do not have to be the aim that drives basic discovery, but communication between the basic scientist and clinical investigators may aid recognition of such targets and their translation to clinical applications. Using one line of investigator-initiated research from his own laboratory as an example, the author emphasizes that basic discovery must be hypothesis driven and allowed to follow its logical sequence. Finding treatments, while always an aim of biomedical research, may arise as a result of basic studies that were not originally aimed at a target of translational research. PMID:22781556

Medical students’ attitudes towards early clinical exposure in Iran

PubMed Central

Khabaz Mafinejad, Mahboobeh; Peiman, Soheil; Khajavirad, Nasim; Mirabdolhagh Hazaveh, Mojgan; Edalatifard, Maryam; Allameh, Seyed-Farshad; Naderi, Neda; Foroumandi, Morteza; Afshari, Ali; Asghari, Fariba

2016-01-01

Objectives This study was carried out to investigate the medical students’ attitudes towards early clinical exposure at Tehran University of Medical Sciences. Methods A cross-sectional study was conducted during 2012-2015. A convenience sample of 298 first- and second-year students, enrolled in the undergraduate medical curriculum, participated in an early clinical exposure program. To collect data from medical students, a questionnaire consisting of open-ended questions and structured questions, rated on a five-point Likert scale, was used to investigate students’ attitudes toward early clinical exposure. Results Of the 298 medical students, 216 (72%) completed the questionnaires. The results demonstrated that medical students had a positive attitude toward early clinical exposure. Most students (80.1%) stated that early clinical exposure could familiarize them with the role of basic sciences knowledge in medicine and how to apply this knowledge in clinical settings. Moreover, 84.5% of them believed that early clinical exposure increased their interest in medicine and encouraged them to read more. Furthermore, content analysis of the students’ responses uncovered three main themes of early clinical exposure, were considered helpful to improve learning: “integration of theory and practice”, “interaction with others and professional development” and “desire and motivation for learning medicine”. Conclusions Medical students found their first experience with clinical setting valuable. Providing clinical exposure in the initial years of medical curricula and teaching the application of basic sciences knowledge in clinical practice can enhance students’ understanding of the role they will play in the future as a physician. PMID:27318794

Doctoral programs to train future leaders in clinical and translational science.

PubMed

Switzer, Galen E; Robinson, Georgeanna F W B; Rubio, Doris M; Fowler, Nicole R; Kapoor, Wishwa N

2013-09-01

Although the National Institutes of Health (NIH) has made extensive investments in educational programs related to clinical and translational science (CTS), there has been no systematic investigation of the number and characteristics of PhD programs providing training to future leaders in CTS. The authors undertook to determine the number of institutions that, having had received NIH-funded Clinical and Translational Science Awards (CTSAs), currently had or were developing PhD programs in CTS; to examine differences between programs developed before and after CTSA funding; and to provide detailed characteristics of new programs. In 2012, CTS program leaders at the 60 CTSA-funded institutions completed a cross-sectional survey focusing on four key domains related to PhD programs in CTS: program development and oversight; students; curriculum and research; and milestones. Twenty-two institutions had fully developed PhD programs in CTS, and 268 students were earning PhDs in this new field; 13 institutions were planning PhD programs. New programs were more likely to have fully developed PhD competencies and more likely to include students in medical school, students working only on their PhD, students working on a first doctoral degree, and students working in T1 translational research. They were less likely to include physicians and students working in clinical or T2 research. Although CTS PhD programs have similarities, they also vary in their characteristics and management of students. This may be due to diversity in translational science itself or to the relative infancy of CTS as a discipline.

A snapshot of translational research funded by the National Institutes of Health (NIH): A case study using behavioral and social science research awards and Clinical and Translational Science Awards funded publications.

PubMed

Han, Xueying; Williams, Sharon R; Zuckerman, Brian L

2018-01-01

The translation of biomedical research from basic knowledge to application has been a priority at the National Institute of Health (NIH) for many years. Tracking the progress of scientific research and knowledge through the translational process is difficult due to variation in the definition of translational research as well as the identification of benchmarks for the spread and application of biomedical research; quantitatively tracking this process is even more difficult. Using a simple and reproducible method to assess whether publications are translational, we examined NIH R01 behavioral and social science research (BSSR) awards funded between 2008 and 2014 to determine whether there are differences in the percent of translational research publications produced by basic and applied research awards. We also assessed the percent of translational research publications produced by the Clinical and Translational Science Awards (CTSA) program to evaluate whether targeted translational research awards result in increased translational research. We found that 3.9% of publications produced by basic research awards were translational; that the percent of translational research publications produced by applied research awards is approximately double that of basic research awards (7.4%); and that targeted translational research awards from the CTSA program produced the highest percentage of translational research publications (13.4%). In addition, we assessed differences in time to first publication, time to first citation, and publication quality by award type (basic vs. applied), and whether an award (or publication) is translational.

A snapshot of translational research funded by the National Institutes of Health (NIH): A case study using behavioral and social science research awards and Clinical and Translational Science Awards funded publications

PubMed Central

Williams, Sharon R.; Zuckerman, Brian L.

2018-01-01

The translation of biomedical research from basic knowledge to application has been a priority at the National Institute of Health (NIH) for many years. Tracking the progress of scientific research and knowledge through the translational process is difficult due to variation in the definition of translational research as well as the identification of benchmarks for the spread and application of biomedical research; quantitatively tracking this process is even more difficult. Using a simple and reproducible method to assess whether publications are translational, we examined NIH R01 behavioral and social science research (BSSR) awards funded between 2008 and 2014 to determine whether there are differences in the percent of translational research publications produced by basic and applied research awards. We also assessed the percent of translational research publications produced by the Clinical and Translational Science Awards (CTSA) program to evaluate whether targeted translational research awards result in increased translational research. We found that 3.9% of publications produced by basic research awards were translational; that the percent of translational research publications produced by applied research awards is approximately double that of basic research awards (7.4%); and that targeted translational research awards from the CTSA program produced the highest percentage of translational research publications (13.4%). In addition, we assessed differences in time to first publication, time to first citation, and publication quality by award type (basic vs. applied), and whether an award (or publication) is translational. PMID:29742129

Mirrors in early clinical photography (1862-1882): a descriptive study.

PubMed

Horgmo, Øystein H

2015-01-01

In the mid-nineteenth century, photographers used mirrors to document different views of a patient in the same image. The first clinical photographs were taken by portrait photographers. As conventions for clinical photography were not yet established, early clinical photographs resemble contemporary portraits. The use of mirrors in clinical photography probably originated from the portrait studios, as several renowned photographers employed mirrors in their studio portraits. Clinical photographs taken for the US Army Medical Museum between 1862 and 1882 show different ways of employing this mirror technique.

Clinical and translational research in Pneumocystis and Pneumocystis pneumonia*

PubMed Central

Huang, L.

2011-01-01

Pneumocystis pneumonia (PcP) remains a significant cause of morbidity and mortality in immunocompromised persons, especially those with human immunodeficiency virus (HIV) infection. Pneumocystis colonization is described increasingly in a wide range of immunocompromised and immunocompetent populations and associations between Pneumocystis colonization and significant pulmonary diseases such as chronic obstructive pulmonary disease (COPD) have emerged. This mini-review summarizes recent advances in our clinical understanding of Pneumocystis and PcP, describes ongoing areas of clinical and translational research, and offers recommendations for future clinical research from researchers participating in the “First centenary of the Pneumocystis discovery”. PMID:21395200

Barriers to implementing evidence-based clinical guidelines: A survey of early adopters

PubMed Central

Spallek, Heiko; Song, Mei; Polk, Deborah E; Bekhuis, Tanja; Frantsve-Hawley, Julie; Aravamudhan, Krishna

2010-01-01

Objective The purpose of this study is to identify barriers that early-adopting dentists perceive as common and challenging when implementing recommendations from evidence-based (EB) clinical guidelines. Method This is a cross-sectional study. Dentists who attended the 2008 Evidence-based Dentistry Champion Conference were eligible for inclusion. Forty-three dentists (34%) responded to a 22-item questionnaire administered online. Two investigators independently coded and categorized responses to open-ended items. Descriptive statistics were computed to assess the frequency of barriers and perceived challenges. Results The most common barriers to implementation are difficulty in changing current practice model, resistance and criticism from colleagues, and lack of trust in evidence or research. Barriers perceived as serious problems have to do with lack of up-to-date evidence, lack of clear answers to clinical questions, and contradictory information in the scientific literature. Conclusions Knowledge of barriers will help improve translation of biomedical research for dentists. Information in guidelines needs to be current, clear, and simplified for use at chairside; dentists’ fears need to be addressed. PMID:21093800

Assessment of Translational and Interdisciplinary Clinical Research at an Oklahoma Health Sciences Center

PubMed Central

Dao, Hanh Dung; Kota, Pravina; James, Judith A.; Stoner, Julie A.; Akins, Darrin R.

2015-01-01

Purpose In response to National Institutes of Health initiatives to improve translation of basic science discoveries we surveyed faculty to assess patterns of and barriers to translational research in Oklahoma. Methods An online survey was administered to University of Oklahoma Health Sciences Center, College of Medicine faculty, which included demographic and research questions. Results Responses were received from 126 faculty members (24%). Two-thirds spent ≥20% time on research; among these, 90% conduct clinical and translational research. Identifying funding; recruiting research staff and participants; preparing reports and agreements; and protecting research time were commonly perceived as at least moderate barriers to conducting research. While respondents largely collaborated within their discipline, clinical investigators were more likely than basic science investigators to engage in interdisciplinary research. Conclusion While engagement in translational research is common, specific barriers impact the research process. This could be improved through an expanded interdisciplinary collaboration and research support structure. PMID:26242016

Risk factors associated with early implant failure: A 5-year retrospective clinical study.

PubMed

Olmedo-Gaya, Maris Victoria; Manzano-Moreno, Francisco J; Cañaveral-Cavero, Esther; de Dios Luna-del Castillo, Juan; Vallecillo-Capilla, Manuel

2016-02-01

The replacement of lost teeth with dental implants is a widespread treatment whose associated problems are also frequently encountered. Nevertheless, the factors associated with early implant failure have not been well documented. Further analyses of the factors influencing osseointegration establishment are required to maximize the predictability of the procedure and minimize implant failures. The purpose of this retrospective clinical study was to explore the association between possible risk factors and early implant failure. This retrospective clinical study evaluated 142 participants who received 276 external connection BTI implants between 2007 and 2011. Participant variables (age, sex, systemic disease, tobacco use, alcohol consumption, bruxism, and degree of periodontal disease), implant variables (type of edentulism, localization, area, diameter, length, and bone quality), intervention variables (expansion mechanisms, sinus augmentation techniques, bone regeneration, and implant insertion), and postoperative variables (presence of pain/inflammation at 1 week postsurgery) were studied. A multilevel logistic regression model (mixed effects-type model) was used to determine the influence of variables on early implant failure. Early implant failure was significantly associated with the male sex (P=.001), severe periodontal disease (P=.005), short implants (P=.001), expansion technique (P=.002), and postoperative pain/inflammation at 1 week postsurgery (P<.001). Early dental implant failure is more frequent in men and in individuals with severe periodontal disease, short implants, pain/inflammation at 1 week postsurgery, or bone expansion treatment. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Making the Leap: the Translation of Innovative Surgical Devices From the Laboratory to the Operating Room.

PubMed

Marcus, Hani J; Payne, Christopher J; Hughes-Hallett, Archie; Gras, Gauthier; Leibrandt, Konrad; Nandi, Dipankar; Yang, Guang-Zhong

2016-06-01

To determine the rate and extent of translation of innovative surgical devices from the laboratory to first-in-human studies, and to evaluate the factors influencing such translation. Innovative surgical devices have preceded many of the major advances in surgical practice. However, the process by which devices arising from academia find their way to translation remains poorly understood. All biomedical engineering journals, and the 5 basic science journals with the highest impact factor, were searched between January 1993 and January 2000 using the Boolean search term "surgery OR surgeon OR surgical". Articles were included if they described the development of a new device and a surgical application was described. A recursive search of all citations to the article was performed using the Web of Science (Thompson-Reuters, New York, NY) to identify any associated first-in-human studies published by January 2015. Kaplan-Meier curves were constructed for the time to first-in-human studies. Factors influencing translation were evaluated using log-rank and Cox proportional hazards models. A total of 8297 articles were screened, and 205 publications describing unique devices were identified. The probability of a first-in-human at 10 years was 9.8%. Clinical involvement was a significant predictor of a first-in-human study (P = 0.02); devices developed with early clinical collaboration were over 6 times more likely to be translated than those without [RR 6.5 (95% confidence interval 0.9-48)]. These findings support initiatives to increase clinical translation through improved interactions between basic, translational, and clinical researchers.

The structure of clinical translation: efficiency, information, and ethics.

PubMed

Kimmelman, Jonathan; London, Alex John

2015-01-01

The so-called drug pipeline is not really about drugs and not much like a pipeline. It is really about the production and dissemination of information, and it is much more like a web. The misunderstanding leads to a poor understanding of what's wrong with clinical translation and how it can be improved.

Clinical and Translational Research Studios: A Multidisciplinary Internal Support Program

PubMed Central

Byrne, Daniel W.; Biaggioni, Italo; Bernard, Gordon R.; Helmer, Tara T.; Boone, Leslie R.; Pulley, Jill M.; Edwards, Terri; Dittus, Robert S.

2012-01-01

The Vanderbilt Institute for Clinical and Translational Research implemented the “Studio” Program in 2007 to bring together experts to provide free, structured, project-specific feedback for medical researchers. Studios are a series of integrated, dynamic, and interactive roundtable discussions that bring relevant research experts from diverse academic disciplines together to focus on a specific research project at a specific stage. Vanderbilt’s Clinical and Translational Science Award supports the program, which is designed to improve the quality and impact of biomedical research. In this article, the authors describe the program’s design, and they provide an evaluation of its first four years. After an investigator completes a brief online studio application, a studio “manager” reviews the request, assembles a panel of 3 to 6 experts (research faculty from multiple disciplines), and circulates the pre-review materials electronically. Investigators can request one of seven studio formats: hypothesis generation, study design, grant review, implementation, analysis and interpretation, manuscript review, or translation. A studio moderator leads each studio session, managing the time (90 minutes) and discussion to optimize the usefulness of the session for the investigator. Feedback from the 157 studio sessions in the first four years has been overwhelmingly positive. Investigators have indicated that their studios have improved the quality of their science (99%; 121/122 responses), and experts have reported that the studios have been a valuable use of their time (98%; 398/406 responses). To achieve the health goals of the 21st century, researchers from multiple disciplines must bridge their differences and together address the challenging problems that face us. -- The Institute of Medicine, 20011 PMID:22722360

Spanish Translation and Cross-Language Validation of a Sleep Habits Questionnaire for Use in Clinical and Research Settings

PubMed Central

Baldwin, Carol M.; Choi, Myunghan; McClain, Darya Bonds; Celaya, Alma; Quan, Stuart F.

2012-01-01

Study Objectives: To translate, back-translate and cross-language validate (English/Spanish) the Sleep Heart Health Study Sleep Habits Questionnaire for use with Spanish-speakers in clinical and research settings. Methods: Following rigorous translation and back-translation, this cross-sectional cross-language validation study recruited bilingual participants from academic, clinic, and community-based settings (N = 50; 52% women; mean age 38.8 ± 12 years; 90% of Mexican heritage). Participants completed English and Spanish versions of the Sleep Habits Questionnaire, the Epworth Sleepiness Scale, and the Acculturation Rating Scale for Mexican Americans II one week apart in randomized order. Psychometric properties were assessed, including internal consistency, convergent validity, scale equivalence, language version intercorrelations, and exploratory factor analysis using PASW (Version18) software. Grade level readability of the sleep measure was evaluated. Results: All sleep categories (duration, snoring, apnea, insomnia symptoms, other sleep symptoms, sleep disruptors, restless legs syndrome) showed Cronbach α, Spearman-Brown coefficients and intercorrelations ≥ 0.700, suggesting robust internal consistency, correlation, and agreement between language versions. The Epworth correlated significantly with snoring, apnea, sleep symptoms, restless legs, and sleep disruptors) on both versions, supporting convergent validity. Items loaded on 4 factors accounted for 68% and 67% of the variance on the English and Spanish versions, respectively. Conclusions: The Spanish-language Sleep Habits Questionnaire demonstrates conceptual and content equivalency. It has appropriate measurement properties and should be useful for assessing sleep health in community-based clinics and intervention studies among Spanish-speaking Mexican Americans. Both language versions showed readability at the fifth grade level. Further testing is needed with larger samples. Citation: Baldwin CM

Translational science: past, present, and future.

PubMed

Curry, Stephen H

2008-02-01

The concept of translational science is at least 15 years old. However, in its most recent incarnation, it represents the identification of a funding category designed to encourage academic participation in a critical stage of the drug discovery and product development process. It is hoped that this will make the process both shorter and more efficient. In this review, the author first considers the historical development of the pharmaceutical R&D process. The place of translational science in the process, the scientific techniques involved, and aspects of the business environment necessary for its success are then considered. Translational science does not displace preclinical development. Both concepts are relevant to the paramount importance of successfully and expeditiously bridging the gap between preclinical science and clinical testing, "from bench to bedside." Translational science is particularly likely to stimulate biomarker research in the universities and related business community and will probably give a modest boost to early clinical testing and commercialization of discoveries within the academic setting. Whether there will be a consequent improvement in the quality and efficiency of the overall process remains to be seen.

Alzheimer's Therapeutics: Translation of Preclinical Science to Clinical Drug Development

PubMed Central

Savonenko, Alena V; Melnikova, Tatiana; Hiatt, Andrew; Li, Tong; Worley, Paul F; Troncoso, Juan C; Wong, Phil C; Price, Don L

2012-01-01

Over the past three decades, significant progress has been made in understanding the neurobiology of Alzheimer's disease. In recent years, the first attempts to implement novel mechanism-based treatments brought rather disappointing results, with low, if any, drug efficacy and significant side effects. A discrepancy between our expectations based on preclinical models and the results of clinical trials calls for a revision of our theoretical views and questions every stage of translation—from how we model the disease to how we run clinical trials. In the following sections, we will use some specific examples of the therapeutics from acetylcholinesterase inhibitors to recent anti-Aβ immunization and γ-secretase inhibition to discuss whether preclinical studies could predict the limitations in efficacy and side effects that we were so disappointed to observe in recent clinical trials. We discuss ways to improve both the predictive validity of mouse models and the translation of knowledge between preclinical and clinical stages of drug development. PMID:21937983

Culture in Translation and Translation Studies.

ERIC Educational Resources Information Center

Schaffner, Christina

1994-01-01

Reviews the evolution of translation from an exchange of information within and across cultural boundaries to its current status as a scholarly endeavor. Translations may have far-reaching effects in the target and source culture. Translators should be cognizant of the foreign language and culture in order to successfully realize their role as…

Health Extension and Clinical and Translational Science: An Innovative Strategy for Community Engagement.

PubMed

Kaufman, Arthur; Rhyne, Robert L; Anastasoff, Juliana; Ronquillo, Francisco; Nixon, Marnie; Mishra, Shiraz; Poola, Charlene; Page-Reeves, Janet; Nkouaga, Carolina; Cordova, Carla; Larson, Richard S

Health Extension Regional Officers (HEROs) through the University of New Mexico Health Sciences Center (UNMHSC) help to facilitate university-community engagement throughout New Mexico. HEROs, based in communities across the state, link priority community health needs with university resources in education, service, and research. Researchers' studies are usually aligned with federal funding priorities rather than with health priorities expressed by communities. To help overcome this misalignment, the UNM Clinical and Translational Science Center (CTSC) provides partial funding for HEROs to bridge the divide between research priorities of UNMHSC and health priorities of the state's communities. A bidirectional partnership between HEROs and CTSC researchers was established, which led to: 1) increased community engaged studies through the CTSC, 2) the HERO model itself as a subject of research, 3) a HERO-driven increase in local capacity in scholarship and grant writing, and 4) development of training modules for investigators and community stakeholders on community-engaged research. As a result, 5 grants were submitted, 4 of which were funded, totaling $7,409,002.00, and 3 research articles were published. Health extension can serve as a university-funded, community-based bridge between community health needs and Clinical and Translational Science Award (CTSA) research capacity, opening avenues for translational research. © Copyright 2017 by the American Board of Family Medicine.

Lost in translation: assessing effectiveness of focus group questioning techniques to develop improved translation of terminology used in HIV prevention clinical trials.

PubMed

Mack, Natasha; Ramirez, Catalina B; Friedland, Barbara; Nnko, Soori

2013-01-01

Achieving participant comprehension has proven to be one of the most difficult, practical, and ethical challenges of HIV prevention clinical trials. It becomes even more challenging when local languages do not have equivalent scientific and technical vocabularies, rendering communication of scientific concepts in translated documents extremely difficult. Even when bilingual lexicons are developed, there is no guarantee that participants understand the terminology as translated. We conducted twelve focus groups with women of reproductive age in Mwanza, Tanzania to explore the effectiveness of four questioning techniques for: (1) assessing participants' familiarity with existing technical terms and concepts, (2) generating a list of acceptable technical and non-technical terms, (3) testing our definitions of technical terms, and (4) verifying participants' preferences for terms. Focus groups were transcribed, translated, and qualitatively analyzed. A translation process that uses all four questioning techniques in a step-wise approach is an effective way to establish a baseline understanding of participants' familiarity with research terms, to develop and test translatable definitions, and to identify participants' preferred terminology for international HIV clinical research. This may help to ensure that important concepts are not "lost in translation." The results emphasize the importance of using a variety of techniques depending on the level of participant familiarity with research concepts, the existence of colloquial or technical terms in the target language, and the inherent complexity of the terms.

Translation and cross-cultural adaptation of the Clinical Competence Questionnaire for use in Brazil.

PubMed

Kwiatkoski, Danielle Ritter; Mantovani, Maria de Fátima; Pereira, Evani Marques; Bortolato-Major, Carina; Mattei, Ângela Taís; Peres, Aida Maris

2017-06-05

translating and transculturally adapting the Clinical Competence Questionnaire to Brazilian senior undergraduate Nursing students, as well as measuring psychometric properties of the questionnaire. a methodological study carried out in six steps: translation of the Clinical Competence Questionnaire instrument, consensus of the translations, back-translation, analysis by an expert committee, pre-testing and then presentation of the cross-cultural adaptation process to the developers. Psychometric properties were measured using Cronbach's alpha, intraclass correlation coefficient and content validity index. the instrument was translated, transculturally adapted and its final version consisted of 48 items. Cronbach's alpha coefficient was 0.90, and the agreement index of the items was 99% for students and 98% for evaluators. the Clinical Competence Questionnaire was translated and adapted to Brazilian students, and the psychometric properties of the Portuguese version of the questionnaire presented satisfactory internal consistency regarding the studied sample. traduzir e adaptar transculturalmente o Clinical Competence Questionnaire aos estudantes brasileiros concluintes da graduação em enfermagem, bem como mensurar as propriedades psicométricas do questionário. estudo metodológico realizado em seis etapas: tradução do instrumento Clinical Competence Questionnaire, consenso das traduções, retrotradução, análise pelo comitê de especialistas, pré-teste e apresentação do processo de adaptação transcultural para os desenvolvedores. As propriedades psicométricas foram mensuradas utilizando-se o alfa de Cronbach, coeficiente de correlação intraclasse e índice de validade de conteúdo. o instrumento foi traduzido, adaptado transculturalmente e sua versão final foi constituída de 48 itens. O coeficiente alfa de Cronbach foi de 0,90, e o índice de concordância dos itens foi de 99% para os estudantes e de 98% para os avaliadores. o Clinical Competence

Strengthening the Career Development of Clinical Translational Scientist Trainees: A Consensus Statement of the Clinical Translational Science Award (CTSA) Research Education and Career Development Committees

PubMed Central

Meyers, Frederick J.; Begg, Melissa D.; Fleming, Michael; Merchant, Carol

2012-01-01

Abstract  The challenges for scholars committed to successful careers in clinical and translational science are increasingly well recognized. The Education and Career Development (EdCD) of the national Clinical and Translational Science Award consortium gathered thought leaders to propose sustainable solutions and an agenda for future studies that would strengthen the infrastructure across the spectrum of pre‐ and postdoctoral, MD and PhD, scholars. Six consensus statements were prepared that include: (1) the requirement for career development of a qualitatively different investigator; (2) the implications of interdisciplinary science for career advancement including institutional promotion and tenure actions that were developed for discipline‐specific accomplishments; (3) the need for long‐term commitment of institutions to scholars; (4) discipline‐specific curricula are still required but curricula designed to promote team work and interdisciplinary training will promote innovation; (5) PhD trainees have many pathways to career satisfaction and success; and (6) a centralized infrastructure to enhance and reward mentoring is required. Several themes cut across all of the recommendations including team science, innovation, and sustained institutional commitment. Implied themes include an effective and diverse job force and the requirement for a well‐crafted public policy that supports continued investments in science education. Clin Trans Sci 2012; Volume #: 1–6 PMID:22507118

Strengthening the career development of clinical translational scientist trainees: a consensus statement of the Clinical Translational Science Award (CTSA) Research Education and Career Development Committees.

PubMed

Meyers, Frederick J; Begg, Melissa D; Fleming, Michael; Merchant, Carol

2012-04-01

The challenges for scholars committed to successful careers in clinical and translational science are increasingly well recognized. The Education and Career Development (EdCD) of the national Clinical and Translational Science Award consortium gathered thought leaders to propose sustainable solutions and an agenda for future studies that would strengthen the infrastructure across the spectrum of pre- and postdoctoral, MD and PhD, scholars. Six consensus statements were prepared that include: (1) the requirement for career development of a qualitatively different investigator; (2) the implications of interdisciplinary science for career advancement including institutional promotion and tenure actions that were developed for discipline-specific accomplishments; (3) the need for long-term commitment of institutions to scholars; (4) discipline-specific curricula are still required but curricula designed to promote team work and interdisciplinary training will promote innovation; (5) PhD trainees have many pathways to career satisfaction and success; and (6) a centralized infrastructure to enhance and reward mentoring is required. Several themes cut across all of the recommendations including team science, innovation, and sustained institutional commitment. Implied themes include an effective and diverse job force and the requirement for a well-crafted public policy that supports continued investments in science education. © 2012 Wiley Periodicals, Inc.

Enabling Anyone to Translate Clinically Relevant Ideas to Therapies.

PubMed

Ekins, Sean; Diaz, Natalie; Chung, Julia; Mathews, Paul; McMurtray, Aaron

2017-01-01

How do we inspire new ideas that could lead to potential treatments for rare or neglected diseases, and allow for serendipity that could help to catalyze them? How many potentially good ideas are lost because they are never tested? What if those ideas could have lead to new therapeutic approaches and major healthcare advances? If a clinician or anyone for that matter, has a new idea they want to test to develop a molecule or therapeutic that they could translate to the clinic, how would they do it without a laboratory or funding? These are not idle theoretical questions but addressing them could have potentially huge economic implications for nations. If we fail to capture the diversity of ideas and test them we may also lose out on the next blockbuster treatments. Many of those involved in the process of ideation may be discouraged and simply not know where to go. We try to address these questions and describe how there are options to raising funding, how even small scale investments can foster preclinical or clinical translation, and how there are several approaches to outsourcing the experiments, whether to collaborators or commercial enterprises. While these are not new or far from complete solutions, they are first steps that can be taken by virtually anyone while we work on other solutions to build a more concrete structure for the "idea-hypothesis testing-proof of concept-translation-breakthrough pathway".

Doctoral Programs to Train Future Leaders in Clinical and Translational Science

PubMed Central

Switzer, Galen E.; Robinson, Georgeanna F.W.B.; Rubio, Doris M.; Fowler, Nicole R.; Kapoor, Wishwa N.

2013-01-01

Purpose Although the National Institutes of Health (NIH) has made extensive investments in educational programs related to clinical and translational science (CTS), there has been no systematic investigation of the number and characteristics of PhD programs providing training to future leaders in CTS. The authors undertook to determine the number of institutions that, having had received NIH-funded Clinical and Translational Science Awards (CTSAs), currently had or were developing PhD programs in CTS; to examine differences between programs developed before and after CTSA funding; and to provide detailed characteristics of new programs. Method In 2012, CTS program leaders at the 60 CTSA-funded institutions completed a cross-sectional survey focusing on four key domains related to PhD programs in CTS: program development and oversight; students; curriculum and research; and milestones. Results Twenty-two institutions had fully developed PhD programs in CTS, and 268 students were earning a PhD in this new field; 13 institutions were planning a PhD program. New programs were more likely to have fully developed PhD competencies and more likely to include students in medical school, students working only on their PhD, students working on a first doctoral degree, and students working in T1 translational research. They were less likely to include physicians and students working in clinical or T2 research. Conclusions Although CTS PhD programs have similarities, they also vary in their characteristics and management of students. This may be due to diversity in translational science itself or to the relative infancy of CTS as a discipline. PMID:23899901

Translation and validation of the clinical learning environment, supervision and nurse teacher scale (CLES + T) in Croatian language.

PubMed

Lovrić, Robert; Piškorjanac, Silvija; Pekić, Vlasta; Vujanić, Jasenka; Ratković, Karolina Kramarić; Luketić, Suzana; Plužarić, Jadranka; Matijašić-Bodalec, Dubravka; Barać, Ivana; Žvanut, Boštjan

2016-07-01

Clinical practice is essential to nursing education as it provides experience with patients and work environments that prepare students for future work as nurses. The aim of this study was to translate the "Clinical Learning Environment, Supervision and Nurse Teacher" questionnaire in Croatian language and test its validity and reliability in practice. The study was performed at the Faculty of medicine, Josip Juraj Strossmayer University of Osijek, Croatia in April 2014. The translated questionnaire was submitted to 136 nursing students: 20 males and 116 females. Our results reflected a slightly different factor structure, consisting of four factors. All translated items of the original constructs "Supervisory relationship", "Role of nurse teacher" and "Leadership style of the ward manager" loaded on factor 1. Items of "Pedagogical atmosphere on the ward" are distributed on two factors (3 and 4). The items of "Premises of nursing on the ward" loaded on factor 2. Three items were identified as problematic and iteratively removed from the analysis. The translated version of the aforementioned questionnaire has properties suitable for the evaluation of clinical practice for nursing students within a Croatian context and reflects the specifics of the nursing clinical education in this country. Copyright © 2016 Elsevier Ltd. All rights reserved.

Technology for Large-Scale Translation of Clinical Practice Guidelines: A Pilot Study of the Performance of a Hybrid Human and Computer-Assisted Approach.

PubMed

Van de Velde, Stijn; Macken, Lieve; Vanneste, Koen; Goossens, Martine; Vanschoenbeek, Jan; Aertgeerts, Bert; Vanopstal, Klaar; Vander Stichele, Robert; Buysschaert, Joost

2015-10-09

The construction of EBMPracticeNet, a national electronic point-of-care information platform in Belgium, began in 2011 to optimize quality of care by promoting evidence-based decision making. The project involved, among other tasks, the translation of 940 EBM Guidelines of Duodecim Medical Publications from English into Dutch and French. Considering the scale of the translation process, it was decided to make use of computer-aided translation performed by certificated translators with limited expertise in medical translation. Our consortium used a hybrid approach, involving a human translator supported by a translation memory (using SDL Trados Studio), terminology recognition (using SDL MultiTerm terminology databases) from medical terminology databases, and support from online machine translation. This resulted in a validated translation memory, which is now in use for the translation of new and updated guidelines. The objective of this experiment was to evaluate the performance of the hybrid human and computer-assisted approach in comparison with translation unsupported by translation memory and terminology recognition. A comparison was also made with the translation efficiency of an expert medical translator. We conducted a pilot study in which two sets of 30 new and 30 updated guidelines were randomized to one of three groups. Comparable guidelines were translated (1) by certificated junior translators without medical specialization using the hybrid method, (2) by an experienced medical translator without this support, and (3) by the same junior translators without the support of the validated translation memory. A medical proofreader who was blinded for the translation procedure, evaluated the translated guidelines for acceptability and adequacy. Translation speed was measured by recording translation and post-editing time. The human translation edit rate was calculated as a metric to evaluate the quality of the translation. A further evaluation was made of

Technology for Large-Scale Translation of Clinical Practice Guidelines: A Pilot Study of the Performance of a Hybrid Human and Computer-Assisted Approach

PubMed Central

2015-01-01

Background The construction of EBMPracticeNet, a national electronic point-of-care information platform in Belgium, began in 2011 to optimize quality of care by promoting evidence-based decision making. The project involved, among other tasks, the translation of 940 EBM Guidelines of Duodecim Medical Publications from English into Dutch and French. Considering the scale of the translation process, it was decided to make use of computer-aided translation performed by certificated translators with limited expertise in medical translation. Our consortium used a hybrid approach, involving a human translator supported by a translation memory (using SDL Trados Studio), terminology recognition (using SDL MultiTerm terminology databases) from medical terminology databases, and support from online machine translation. This resulted in a validated translation memory, which is now in use for the translation of new and updated guidelines. Objective The objective of this experiment was to evaluate the performance of the hybrid human and computer-assisted approach in comparison with translation unsupported by translation memory and terminology recognition. A comparison was also made with the translation efficiency of an expert medical translator. Methods We conducted a pilot study in which two sets of 30 new and 30 updated guidelines were randomized to one of three groups. Comparable guidelines were translated (1) by certificated junior translators without medical specialization using the hybrid method, (2) by an experienced medical translator without this support, and (3) by the same junior translators without the support of the validated translation memory. A medical proofreader who was blinded for the translation procedure, evaluated the translated guidelines for acceptability and adequacy. Translation speed was measured by recording translation and post-editing time. The human translation edit rate was calculated as a metric to evaluate the quality of the translation. A

Clinical outcomes of immediate/early loading of dental implants. A literature review of recent controlled prospective clinical studies.

PubMed

Sennerby, L; Gottlow, J

2008-06-01

Two previous reviews have evaluated the clinical outcomes of immediate/early loading of dental implants based on studies published until 2005.(1,2) The aim of the present paper was to review controlled clinical studies on the subject published since 2005 including at least 10 patients in each group followed for at least one year in function. Six comparative studies were found and none of these showed any differences in survival rates or marginal bone loss after one to five years. Most authors used specified inclusion criteria to avoid known risk factors such as soft bone, short implants and bruxism. Data from one randomized study in the edentulous maxilla showed no differences between early and delayed loading in consecutive clinical routine cases including short implants and soft bone. Three additional studies comparing different surfaces or implant designs under immediate loading were reviewed. No differences between implants with a moderately rough or smooth surface topography were observed. The data add to the previous bulk of evidence that various designs of implants can be loaded shortly after their placement in both the mandible and the maxilla. However, one study reported on marginal bone loss around a novel one-piece implant design leading to implant failure which was not seen for control two-piece implants.(3).

Microfluidic-Mass Spectrometry Interfaces for Translational Proteomics.

PubMed

Pedde, R Daniel; Li, Huiyan; Borchers, Christoph H; Akbari, Mohsen

2017-10-01

Interfacing mass spectrometry (MS) with microfluidic chips (μchip-MS) holds considerable potential to transform a clinician's toolbox, providing translatable methods for the early detection, diagnosis, monitoring, and treatment of noncommunicable diseases by streamlining and integrating laborious sample preparation workflows on high-throughput, user-friendly platforms. Overcoming the limitations of competitive immunoassays - currently the gold standard in clinical proteomics - μchip-MS can provide unprecedented access to complex proteomic assays having high sensitivity and specificity, but without the labor, costs, and complexities associated with conventional MS sample processing. This review surveys recent μchip-MS systems for clinical applications and examines their emerging role in streamlining the development and translation of MS-based proteomic assays by alleviating many of the challenges that currently inhibit widespread clinical adoption. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Knowledge translation: a case study on pneumonia research and clinical guidelines in a low- income country.

PubMed

Goyet, Sophie; Barennes, Hubert; Libourel, Therese; van Griensven, Johan; Frutos, Roger; Tarantola, Arnaud

2014-06-26

The process and effectiveness of knowledge translation (KT) interventions targeting policymakers are rarely reported. In Cambodia, a low-income country (LIC), an intervention aiming to provide evidence-based knowledge on pneumonia to health authorities was developed to help update pediatric and adult national clinical guidelines. Through a case study, we assessed the effectiveness of this KT intervention, with the goal of identifying the barriers to KT and suggest strategies to facilitate KT in similar settings. An extensive search for all relevant sources of data documenting the processes of updating adult and pediatric pneumonia guidelines was done. Documents included among others, reports, meeting minutes, and email correspondences. The study was conducted in successive phases: an appraisal of the content of both adult and pediatric pneumonia guidelines; an appraisal of the quality of guidelines by independent experts, using the AGREE-II instrument; a description and modeling of the KT process within the guidelines updating system, using the Unified Modeling Language (UML) tools 2.2; and the listing of the barriers and facilitators to KT we identified during the study. The first appraisal showed that the integration of the KT key messages in pediatric and adult guidelines varied with a better efficiency in the pediatric guidelines. The overall AGREE-II quality assessments scored 37% and 44% for adult and pediatric guidelines, respectively. Scores were lowest for the domains of 'rigor of development' and 'editorial independence.' The UML analysis highlighted that time frames and constraints of the involved stakeholders greatly differed and that there were several missed opportunities to translate on evidence into the adult pneumonia guideline. Seventeen facilitating factors and 18 potential barriers to KT were identified. Main barriers were related to the absence of a clear mandate from the Ministry of Health for the researchers and to a lack of synchronization

Knowledge translation: a case study on pneumonia research and clinical guidelines in a low- income country

PubMed Central

2014-01-01

Background The process and effectiveness of knowledge translation (KT) interventions targeting policymakers are rarely reported. In Cambodia, a low-income country (LIC), an intervention aiming to provide evidence-based knowledge on pneumonia to health authorities was developed to help update pediatric and adult national clinical guidelines. Through a case study, we assessed the effectiveness of this KT intervention, with the goal of identifying the barriers to KT and suggest strategies to facilitate KT in similar settings. Methods An extensive search for all relevant sources of data documenting the processes of updating adult and pediatric pneumonia guidelines was done. Documents included among others, reports, meeting minutes, and email correspondences. The study was conducted in successive phases: an appraisal of the content of both adult and pediatric pneumonia guidelines; an appraisal of the quality of guidelines by independent experts, using the AGREE-II instrument; a description and modeling of the KT process within the guidelines updating system, using the Unified Modeling Language (UML) tools 2.2; and the listing of the barriers and facilitators to KT we identified during the study. Results The first appraisal showed that the integration of the KT key messages in pediatric and adult guidelines varied with a better efficiency in the pediatric guidelines. The overall AGREE-II quality assessments scored 37% and 44% for adult and pediatric guidelines, respectively. Scores were lowest for the domains of ‘rigor of development’ and ‘editorial independence.’ The UML analysis highlighted that time frames and constraints of the involved stakeholders greatly differed and that there were several missed opportunities to translate on evidence into the adult pneumonia guideline. Seventeen facilitating factors and 18 potential barriers to KT were identified. Main barriers were related to the absence of a clear mandate from the Ministry of Health for the researchers

Effect of a Clinical and Translational Science Award institute on grant funding in a major research university.

PubMed

Kabo, Felichism W; Mashour, George A

2017-04-01

Previous studies have examined the impact of Clinical and Translational Science Awards programs on other outcomes, but not on grant seeking. The authors examined the effects on grant seeking of the Michigan Institute for Clinical & Health Research (MICHR), a Clinical and Translational Science Awards institute at the University of Michigan. We assessed over 63,000 grant proposals submitted at the University of Michigan in the years 2002-2012 using data from the university and MICHR's Tracking Metrics and Reporting System. We used a retrospective, observational study of the dynamics of grant-seeking success and award funding. Heckman selection models were run to assess MICHR's relationship with a proposal's success (selection), and subsequently the award's size (outcome). Models were run for all proposals and for clinical and translational research (CTR) proposals alone. Other covariates included proposal classification, type of grant award, academic unit, and year. MICHR had a positive and statistically significant relationship with success for both proposal types. For all grants, MICHR was associated with a 29.6% increase in award size. For CTR grants, MICHR had a statistically nonsignificant relationship with award size. MICHR's infrastructure, created to enable and enhance CTR, has also created positive spillovers for a broader spectrum of research and grant seeking.

Driving CT developments the last mile: case examples of successful and somewhat less successful translations into clinical practice

NASA Astrophysics Data System (ADS)

Sodickson, Aaron D.

2017-03-01

CT technology has advanced rapidly in recent years, yet not all innovations translate readily into clinical practice. Technology advances must meet certain key requirements to make it into routine use: They must provide a well-defined clinical benefit. They must be easy to use and integrate readily into existing workflows, or better still, further streamline these workflows. These requirements heavily favor fully integrated or automated solutions that remove the human factor and provide a reproducible output independent of operator skill level. Further, to achieve these aims, collaboration with the ultimate end users is needed as early as possible in the development cycle, not just at the point of product testing. Technology innovators are encouraged to engage such collaborators even at early stages of feature or product definition. This manuscript highlights these concepts through exploration of challenging areas in CT imaging in an Emergency Department setting. Technique optimization for pulmonary embolus CT is described as an example of successful integration of multiple advances in radiation dose reduction and imaging speed. The typical workflow of a trauma "pan-scan" (incorporating scans from head through pelvis) is described to highlight workflow challenges and opportunities for improvement. Finally, Dual Energy CT is discussed to highlight the undeniable clinical value of the material characterization it provides, yet also its surprisingly slow integration into routine use beyond early adopters.

Mapping the Ethics of Translational Genomics: Situating Return of Results and Navigating the Research-Clinical Divide

PubMed Central

Wolf, Susan M.; Burke, Wylie; Koenig, Barbara A.

2015-01-01

Both bioethics and law have governed human genomics by distinguishing research from clinical practice. Yet the rise of translational genomics now makes this traditional dichotomy inadequate. This paper pioneers a new approach to the ethics of translational genomics. It maps the full range of ethical approaches needed, proposes a “layered” approach to determining the ethics framework for projects combining research and clinical care, and clarifies the key role that return of results can play in advancing translation. PMID:26479558

BRIDG: a domain information model for translational and clinical protocol-driven research.

PubMed

Becnel, Lauren B; Hastak, Smita; Ver Hoef, Wendy; Milius, Robert P; Slack, MaryAnn; Wold, Diane; Glickman, Michael L; Brodsky, Boris; Jaffe, Charles; Kush, Rebecca; Helton, Edward

2017-09-01

It is critical to integrate and analyze data from biological, translational, and clinical studies with data from health systems; however, electronic artifacts are stored in thousands of disparate systems that are often unable to readily exchange data. To facilitate meaningful data exchange, a model that presents a common understanding of biomedical research concepts and their relationships with health care semantics is required. The Biomedical Research Integrated Domain Group (BRIDG) domain information model fulfills this need. Software systems created from BRIDG have shared meaning "baked in," enabling interoperability among disparate systems. For nearly 10 years, the Clinical Data Standards Interchange Consortium, the National Cancer Institute, the US Food and Drug Administration, and Health Level 7 International have been key stakeholders in developing BRIDG. BRIDG is an open-source Unified Modeling Language-class model developed through use cases and harmonization with other models. With its 4+ releases, BRIDG includes clinical and now translational research concepts in its Common, Protocol Representation, Study Conduct, Adverse Events, Regulatory, Statistical Analysis, Experiment, Biospecimen, and Molecular Biology subdomains. The model is a Clinical Data Standards Interchange Consortium, Health Level 7 International, and International Standards Organization standard that has been utilized in national and international standards-based software development projects. It will continue to mature and evolve in the areas of clinical imaging, pathology, ontology, and vocabulary support. BRIDG 4.1.1 and prior releases are freely available at https://bridgmodel.nci.nih.gov . © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Topical Review: Translating Translational Research in Behavioral Science.

PubMed

Hommel, Kevin A; Modi, Avani C; Piazza-Waggoner, Carrie; Myers, James D

2015-01-01

To present a model of translational research for behavioral science that communicates the role of behavioral research at each phase of translation. A task force identified gaps in knowledge regarding behavioral translational research processes and made recommendations regarding advancement of knowledge. A comprehensive model of translational behavioral research was developed. This model represents T1, T2, and T3 research activities, as well as Phase 1, 2, 3, and 4 clinical trials. Clinical illustrations of translational processes are also offered as support for the model. Behavioral science has struggled with defining a translational research model that effectively articulates each stage of translation and complements biomedical research. Our model defines key activities at each phase of translation from basic discovery to dissemination/implementation. This should be a starting point for communicating the role of behavioral science in translational research and a catalyst for better integration of biomedical and behavioral research. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Legacy Clinical Data from the Mission Connect Mild TBI Translational Research Consortium

DTIC Science & Technology

2017-10-01

mTBI) Translational Research Consortium was to improve the diagnosis and treatment of mTBI. We enrolled a total of 88 mTBI patients and 73 orthopedic ...AWARD NUMBER: W81XWH-16-2-0026 TITLE: Legacy Clinical Data from the Mission Connect Mild TBI Translational Research Consortium PRINCIPAL...Annual PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT: Approved for

Translating findings from basic fear research to clinical psychiatry in Puerto Rico

PubMed Central

Quirk, Gregory J.; Martinez, Karen G.; Nazario Rodríguez, Lelis L.

2009-01-01

Recent advances in the neuroscience of classical fear conditioning from both rodent and human studies are beginning to be translated to the psychiatry clinic. In particular, our understanding of fear extinction as a form of “safety learning” holds promise for the treatment of anxiety disorders in which extinction learning is thought to be compromised. The Department of Psychiatry at the UPR, School of Medicine promotes the development of innovative strategies for treating mental health problems. Given the burden resulting from anxiety disorders in Puerto Rico, and the lack of evidence-based treatment practices, there is a pressing need for a future center specializing in the treatment of anxiety related disorders. This center would also serve research and training functions, with the ultimate goal of translating extinction research into clinical practice. This review presents the current developments in extinction research and its relationship to anxiety disorders and treatment. We also analyze the available literature on the epidemiology of anxiety disorders and the existing evidence-based treatments for these conditions. PMID:18246959

Translating ocular biomechanics into clinical practice: current state and future prospects.

PubMed

Girard, Michaël J A; Dupps, William J; Baskaran, Mani; Scarcelli, Giuliano; Yun, Seok H; Quigley, Harry A; Sigal, Ian A; Strouthidis, Nicholas G

2015-01-01

Biomechanics is the study of the relationship between forces and function in living organisms and is thought to play a critical role in a significant number of ophthalmic disorders. This is not surprising, as the eye is a pressure vessel that requires a delicate balance of forces to maintain its homeostasis. Over the past few decades, basic science research in ophthalmology mostly confirmed that ocular biomechanics could explain in part the mechanisms involved in almost all major ophthalmic disorders such as optic nerve head neuropathies, angle closure, ametropia, presbyopia, cataract, corneal pathologies, retinal detachment and macular degeneration. Translational biomechanics in ophthalmology, however, is still in its infancy. It is believed that its use could make significant advances in diagnosis and treatment. Several translational biomechanics strategies are already emerging, such as corneal stiffening for the treatment of keratoconus, and more are likely to follow. This review aims to cultivate the idea that biomechanics plays a major role in ophthalmology and that the clinical translation, lead by collaborative teams of clinicians and biomedical engineers, will benefit our patients. Specifically, recent advances and future prospects in corneal, iris, trabecular meshwork, crystalline lens, scleral and lamina cribrosa biomechanics are discussed.

Translating Ocular Biomechanics into Clinical Practice: Current State and Future Prospects

PubMed Central

Girard, Michaël J.A.; Dupps, William J.; Baskaran, Mani; Scarcelli, Giuliano; Yun, Seok H.; Quigley, Harry A.; Sigal, Ian A.; Strouthidis, Nicholas G.

2014-01-01

Biomechanics – the study of the relationship between forces and function in living organisms – is thought to play a critical role in a significant number of ophthalmic disorders. This is not surprising, as the eye is a pressure vessel that requires a delicate balance of forces to maintain its homeostasis. Over the past few decades, basic science research in ophthalmology mostly confirmed that ocular biomechanics could explain in part the mechanisms involved in almost all major ophthalmic disorders such as optic nerve head neuropathies, angle closure, ametropia, presbyopia, cataract, corneal pathologies, retinal detachment, and macular degeneration. Translational biomechanics in ophthalmology, however, is still in its infancy. It is believed that its use could make significant advances in diagnosis and treatment. Several translational biomechanics strategies are already emerging, such as corneal stiffening for the treatment of keratoconus, and more are likely to follow. This review aims to cultivate the idea that biomechanics plays a major role in ophthalmology and that its clinical translation, lead by collaborative teams of clinicians and biomedical engineers, will benefit our patients. Specifically, recent advances and future prospects in corneal, iris, trabecular meshwork, crystalline lens, scleral and lamina cribrosa biomechanics are discussed. PMID:24832392

Dopamine Transporter Neuroimaging as an Enrichment Biomarker in Early Parkinson's Disease Clinical Trials: A Disease Progression Modeling Analysis.

PubMed

Conrado, Daniela J; Nicholas, Timothy; Tsai, Kuenhi; Macha, Sreeraj; Sinha, Vikram; Stone, Julie; Corrigan, Brian; Bani, Massimo; Muglia, Pierandrea; Watson, Ian A; Kern, Volker D; Sheveleva, Elena; Marek, Kenneth; Stephenson, Diane T; Romero, Klaus

2018-01-01

Given the recognition that disease-modifying therapies should focus on earlier Parkinson's disease stages, trial enrollment based purely on clinical criteria poses significant challenges. The goal herein was to determine the utility of dopamine transporter neuroimaging as an enrichment biomarker in early motor Parkinson's disease clinical trials. Patient-level longitudinal data of 672 subjects with early-stage Parkinson's disease in the Parkinson's Progression Markers Initiative (PPMI) observational study and the Parkinson Research Examination of CEP-1347 Trial (PRECEPT) clinical trial were utilized in a linear mixed-effects model analysis. The rate of worsening in the motor scores between subjects with or without a scan without evidence of dopamine transporter deficit was different both statistically and clinically. The average difference in the change from baseline of motor scores at 24 months between biomarker statuses was -3.16 (90% confidence interval [CI] = -0.96 to -5.42) points. Dopamine transporter imaging could identify subjects with a steeper worsening of the motor scores, allowing trial enrichment and 24% reduction of sample size. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Translation, reliability, and clinical utility of the Melbourne Assessment 2.

PubMed

Gerber, Corinna N; Plebani, Anael; Labruyère, Rob

2017-10-12

The aims were to (i) provide a German translation of the Melbourne Assessment 2 (MA2), a quantitative test to measure unilateral upper limb function in children with neurological disabilities and (ii) to evaluate its reliability and aspects of clinical utility. After its translation into German and approval of the back translation by the original authors, the MA2 was performed and videotaped twice with 30 children with neuromotor disorders. For each participant, two raters scored the video of the first test for inter-rater reliability. To determine test-retest reliability, one rater additionally scored the video of the second test while the other rater repeated the scoring of the first video to evaluate intra-rater reliability. Time needed for rater training, test administration, and scoring was recorded. The four subscale scores showed excellent intra-, inter-rater, and test-retest reliability with intraclass correlation coefficients of 0.90-1.00 (95%-confidence intervals 0.78-1.00). Score items revealed substantial to almost perfect intra-rater reliability (weighted kappa k w  = 0.66-1.00) for the more affected side. Score item inter-rater and test-retest reliability of the same extremity were, with one exception, moderate to almost perfect (k w  = 0.42-0.97; k w  = 0.40-0.89). Furthermore, the MA2 was feasible and acceptable for patients and clinicians. The MA2 showed excellent subscale and moderate to almost perfect score item reliability. Implications for Rehabilitation There is a lack of high-quality studies about psychometric properties of upper limb measurement tools in the neuropediatric population. The Melbourne Assessment 2 is a promising tool for reliable measurement of unilateral upper limb movement quality in the neuropediatric population. The Melbourne Assessment 2 is acceptable and practicable to therapists and patients for routine use in clinical care.

Early clinical outcomes following laparoscopic inguinal hernia repair.

PubMed

Tolver, Mette Astrup

2013-07-01

Laparoscopic inguinal hernia repair (TAPP) has gained increasing popularity because of less post-operative pain and a shorter duration of convalescence compared with open hernia repair technique (Lichtenstein). However, investigation of duration of convalescence with non-restrictive recommendations, and a procedure-specific characterization of the early clinical outcomes after TAPP was lacking. Furthermore, optimization of the post-operative period with fibrin sealant versus tacks for fixation of mesh, and the glucocorticoid dexamethasone versus placebo needed to be investigated in randomized clinical trials. The objective of this PhD thesis was to characterize the early clinical outcomes after TAPP and optimize the post-operative period. The four studies included in this thesis have investigated duration of convalescence and procedure-specific post-operative pain and other early clinical outcomes after TAPP. Furthermore, it has been shown that fibrin sealant can improve the early post-operative period compared with tacks, while dexamethasone showed no advantages apart from reduced use of antiemetics compared with placebo. Based on these findings, and the existing knowledge, 3-5 days of convalescence should be expected when 1 day of convalescence is recommended and future studies should focus on reducing intraabdominal pain after TAPP. Fibrin sealant can optimize the early clinical outcomes but the risk of hernia recurrence and chronic pain needs to be evaluated. Dexamethasone should be investigated in higher doses.

Lost in Translation: Assessing Effectiveness of Focus Group Questioning Techniques to Develop Improved Translation of Terminology Used in HIV Prevention Clinical Trials

PubMed Central

Mack, Natasha; Ramirez, Catalina B.; Friedland, Barbara; Nnko, Soori

2013-01-01

Introduction Achieving participant comprehension has proven to be one of the most difficult, practical, and ethical challenges of HIV prevention clinical trials. It becomes even more challenging when local languages do not have equivalent scientific and technical vocabularies, rendering communication of scientific concepts in translated documents extremely difficult. Even when bilingual lexicons are developed, there is no guarantee that participants understand the terminology as translated. Methods We conducted twelve focus groups with women of reproductive age in Mwanza, Tanzania to explore the effectiveness of four questioning techniques for: (1) assessing participants' familiarity with existing technical terms and concepts, (2) generating a list of acceptable technical and non-technical terms, (3) testing our definitions of technical terms, and (4) verifying participants' preferences for terms. Focus groups were transcribed, translated, and qualitatively analyzed. Results and Discussion A translation process that uses all four questioning techniques in a step-wise approach is an effective way to establish a baseline understanding of participants' familiarity with research terms, to develop and test translatable definitions, and to identify participants' preferred terminology for international HIV clinical research. This may help to ensure that important concepts are not “lost in translation.” The results emphasize the importance of using a variety of techniques depending on the level of participant familiarity with research concepts, the existence of colloquial or technical terms in the target language, and the inherent complexity of the terms. PMID:24040075

Early discharge of patients with pulmonary embolism in daily clinical practice: A prospective observational study comparing clinical gestalt and clinical rules.

PubMed

Vanni, Simone; Becattini, Cecilia; Nazerian, Peiman; Bova, Carlo; Stefanone, Valerio Teodoro; Cimini, Ludovica Anna; Viviani, Gabriele; Caviglioli, Cosimo; Sanna, Michela; Pepe, Giuseppe; Grifoni, Stefano

2018-05-08

To estimate the efficiency and safety of clinicians' gestalt in the identification of patients with pulmonary embolism (PE) candidates for early discharge and to compare the efficiency and safety of clinical gestalt with that of the Pulmonary Embolism Severity Index (PESI), the simplified PESI (sPESI) and the Hestia criteria (HC). Consecutive adult patients presenting to the emergency department of four Italian hospitals with confirmed diagnosis of PE were included. Data for PESI, sPESI and HC assessment were prospectively collected. Patients were managed according to the clinical gestalt of the attending physician, independent of the results of PESI, sPESI and HC. Efficiency was defined as the prevalence of candidates to early discharge. The primary safety measure was the incidence of a composite of venous thromboembolic recurrence, major haemorrhage or all-cause mortality within 30 days. Out of 547 included patients, 178 (32.5%) were judged to be at low risk and discharged within 48 h from presentation. HC identified a higher proportion (41.7%) whereas both PESI (24.1%) and sPESI (18.3%) identified a lower proportion of candidates for early discharge when compared to clinical gestalt (P < 0.01 for all). The incidence of the safety outcome was 2.8% in early-discharged patients according to clinical gestalt and 2.3%, 3.0% and 2.6% in candidates to early discharge according to PESI, sPESI and HC, without differences between strategies. In our cohort, clinical gestalt identified one-third of PE patients for early discharge. Among different strategies HC showed the highest efficiency sharing similar safety with the other strategies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Mapping the Ethics of Translational Genomics: Situating Return of Results and Navigating the Research-Clinical Divide.

PubMed

Wolf, Susan M; Burke, Wylie; Koenig, Barbara A

2015-01-01

Both bioethics and law have governed human genomics by distinguishing research from clinical practice. Yet the rise of translational genomics now makes this traditional dichotomy inadequate. This paper pioneers a new approach to the ethics of translational genomics. It maps the full range of ethical approaches needed, proposes a "layered" approach to determining the ethics framework for projects combining research and clinical care, and clarifies the key role that return of results can play in advancing translation. © 2015 American Society of Law, Medicine & Ethics, Inc.

Current nonclinical testing paradigm enables safe entry to First-In-Human clinical trials: The IQ consortium nonclinical to clinical translational database.

PubMed

Monticello, Thomas M; Jones, Thomas W; Dambach, Donna M; Potter, David M; Bolt, Michael W; Liu, Maggie; Keller, Douglas A; Hart, Timothy K; Kadambi, Vivek J

2017-11-01

The contribution of animal testing in drug development has been widely debated and challenged. An industry-wide nonclinical to clinical translational database was created to determine how safety assessments in animal models translate to First-In-Human clinical risk. The blinded database was composed of 182 molecules and contained animal toxicology data coupled with clinical observations from phase I human studies. Animal and clinical data were categorized by organ system and correlations determined. The 2×2 contingency table (true positive, false positive, true negative, false negative) was used for statistical analysis. Sensitivity was 48% with a 43% positive predictive value (PPV). The nonhuman primate had the strongest performance in predicting adverse effects, especially for gastrointestinal and nervous system categories. When the same target organ was identified in both the rodent and nonrodent, the PPV increased. Specificity was 84% with an 86% negative predictive value (NPV). The beagle dog had the strongest performance in predicting an absence of clinical adverse effects. If no target organ toxicity was observed in either test species, the NPV increased. While nonclinical studies can demonstrate great value in the PPV for certain species and organ categories, the NPV was the stronger predictive performance measure across test species and target organs indicating that an absence of toxicity in animal studies strongly predicts a similar outcome in the clinic. These results support the current regulatory paradigm of animal testing in supporting safe entry to clinical trials and provide context for emerging alternate models. Copyright © 2017 Elsevier Inc. All rights reserved.

Sustaining the Clinical Translational Research Workforce: Training and Empowering the Next Generation of Investigators

PubMed Central

Yin, Helen L.; Gabrilove, Janice; Jackson, Rebecca; Sweeney, Carol; Fair, Alecia M.; Toto, Robert

2015-01-01

There is mounting concern that clinician scientists are a vanishing species, and that the pipeline for clinical translational research (CTR) investigators is in jeopardy. For the majority of current junior CTR investigators, the career path involves first obtaining a National Institutes of Health (NIH) funded K-type career development award, particularly K08 and K23, and subsequently an NIH R01. This transition, popularly referred to as K2R, is a major hurdle with a low success rate and gaps in funding. In this Perspective, the authors identify factors that facilitate K2R transition and important aspects of increasing and sustaining the pipeline of CTR investigators. They also highlight significant differences in success rates of women and those underrepresented in biomedical research. Early career exposure to research methodology, protected time, multidisciplinary mentoring, and institutional “culture shift” are important for fostering and rewarding team science. Mentoring is the single most important contributor to K2R success, and emerging evidence suggests that formal mentor training and team mentoring are effective. Leadership training can empower junior investigators to thrive as independent CTR investigators. Future research should focus on delineating the difference between essential and supplemental factors to achieve this transition, and mentoring methods that foster success, including those that promote K2R transition of women and those underrepresented in biomedical research. The Clinical Translational Science Awards National Consortium is well positioned to test existing models aimed at shortening the timeframe, increasing the rate of K2R transition, and identifying strategies that improve success. PMID:26414054

SHAPING A NEW GENERATION OF HISPANIC CLINICAL AND TRANSLATIONAL RESEARCHERS ADDRESSING MINORITY HEALTH AND HEALTH DISPARITIES

PubMed Central

Estape, Estela S.; Segarra, Barbara; Baez, Adriana; Huertas, Aracelis; Diaz, Clemente; Frontera, Walter

2012-01-01

In 2011, research educators face significant challenges. Training programs in Clinical and Translational Research need to develop or enhance their curriculum to comply with new scientific trends and government policies. Curricula must impart the skills and competencies needed to help facilitate the dissemination and transfer of scientific advances at a faster pace than current health policy and practice. Clinical and translational researchers are facing also the need of new paradigms for effective collaboration, and resource sharing while using the best educational models. Both government and public policy makers emphasize addressing the goals of improving health quality and elimination of health disparities. To help achieve this goal, our academic institution is taking an active role and striving to develop an environment that fosters the career development of clinical and translational researchers. Consonant with this vision, in 2002 the University of Puerto Rico, Medical Sciences Campus School of Health Professions and School of Medicine initiated a multidisciplinary post-doctoral Master of Science in Clinical Research focused in training Hispanics who will address minority health and health disparities research. Recently, we proposed a curriculum revision to enhance this commitment in promoting competency-based curricula for clinician-scientists in clinical and translational sciences. The revised program will be a post-doctoral Master of Science in Clinical and Translational Research (MCTR), expanding its outreach by actively engaging in establishing new collaborations and partnerships that will increase our capability to diversify our educational efforts and make significant contributions to help reduce and eliminate the gap in health disparities. PMID:22263296

Challenges in translating vascular tissue engineering to the pediatric clinic.

PubMed

Duncan, Daniel R; Breuer, Christopher K

2011-10-14

The development of tissue-engineered vascular grafts for use in cardiovascular surgery holds great promise for improving outcomes in pediatric patients with complex congenital cardiac anomalies. Currently used synthetic grafts have a number of shortcomings in this setting but a tissue engineering approach has emerged in the past decade as a way to address these limitations. The first clinical trial of this technology showed that it is safe and effective but the primary mode of graft failure is stenosis. A variety of murine and large animal models have been developed to study and improve tissue engineering approaches with the hope of translating this technology into routine clinical use, but challenges remain. The purpose of this report is to address the clinical problem and review recent advances in vascular tissue engineering for pediatric applications. A deeper understanding of the mechanisms of neovessel formation and stenosis will enable rational design of improved tissue-engineered vascular grafts.

Translating Alcohol Research: Opportunities and Challenges.

PubMed

Batman, Angela M; Miles, Michael F

2015-01-01

Alcohol use disorder (AUD) and its sequelae impose a major burden on the public health of the United States, and adequate long-term control of this disorder has not been achieved. Molecular and behavioral basic science research findings are providing the groundwork for understanding the mechanisms underlying AUD and have identified multiple candidate targets for ongoing clinical trials. However, the translation of basic research or clinical findings into improved therapeutic approaches for AUD must become more efficient. Translational research is a multistage process of stream-lining the movement of basic biomedical research findings into clinical research and then to the clinical target populations. This process demands efficient bidirectional communication across basic, applied, and clinical science as well as with clinical practitioners. Ongoing work suggests rapid progress is being made with an evolving translational framework within the alcohol research field. This is helped by multiple interdisciplinary collaborative research structures that have been developed to advance translational work on AUD. Moreover, the integration of systems biology approaches with collaborative clinical studies may yield novel insights for future translational success. Finally, appreciation of genetic variation in pharmacological or behavioral treatment responses and optimal communication from bench to bedside and back may strengthen the success of translational research applications to AUD.

A Comparative Study of "Google Translate" Translations: An Error Analysis of English-to-Persian and Persian-to-English Translations

ERIC Educational Resources Information Center

Ghasemi, Hadis; Hashemian, Mahmood

2016-01-01

Both lack of time and the need to translate texts for numerous reasons brought about an increase in studying machine translation with a history spanning over 65 years. During the last decades, Google Translate, as a statistical machine translation (SMT), was in the center of attention for supporting 90 languages. Although there are many studies on…

Application of statistical machine translation to public health information: a feasibility study.

PubMed

Kirchhoff, Katrin; Turner, Anne M; Axelrod, Amittai; Saavedra, Francisco

2011-01-01

Accurate, understandable public health information is important for ensuring the health of the nation. The large portion of the US population with Limited English Proficiency is best served by translations of public-health information into other languages. However, a large number of health departments and primary care clinics face significant barriers to fulfilling federal mandates to provide multilingual materials to Limited English Proficiency individuals. This article presents a pilot study on the feasibility of using freely available statistical machine translation technology to translate health promotion materials. The authors gathered health-promotion materials in English from local and national public-health websites. Spanish versions were created by translating the documents using a freely available machine-translation website. Translations were rated for adequacy and fluency, analyzed for errors, manually corrected by a human posteditor, and compared with exclusively manual translations. Machine translation plus postediting took 15-53 min per document, compared to the reported days or even weeks for the standard translation process. A blind comparison of machine-assisted and human translations of six documents revealed overall equivalency between machine-translated and manually translated materials. The analysis of translation errors indicated that the most important errors were word-sense errors. The results indicate that machine translation plus postediting may be an effective method of producing multilingual health materials with equivalent quality but lower cost compared to manual translations.

From Idea to Product--Translating Knowledge between the Lab and the Clinic

ERIC Educational Resources Information Center

Ali, Ayfer Habib

2012-01-01

This dissertation is composed of three essays looking at innovation at Academic Medical Centers. It tries to empirically explore the problem of translating knowledge from the laboratory bench to the clinic and from the clinic to the bench. Chapter 1, co-authored with Iain Cockburn, establishes the importance of in-house complementary knowledge in…

Integrating Simulation Scenarios and Clinical Practices Guided by Concepts of Translational Medicine

ERIC Educational Resources Information Center

Yang, Jing; Huang, Si-min; Li, Ze-jian; Feng, Lie; Lu, Chun-ting

2018-01-01

Purpose: To develop a novel method for closely and effectively integrating simulation scenarios and clinical practices to improve clinical skills training in the concepts of translational medicine. Methods: Forty-two and 38 third-year medical students in the classes of 2010 and 2009 at Jinan University were selected as an observation group and a…

National Center for Advancing Translational Sciences

MedlinePlus

... Models Core Technologies Clinical Innovation Clinical and Translational Science Awards Program Rare Diseases Clinical Research Network Patient ... to our monthly e-newsletter. About Translation Translational Science Spectrum Explore the full spectrum of translational science, ...

A data-rich recruitment core to support translational clinical research.

PubMed

Kost, Rhonda G; Corregano, Lauren M; Rainer, Tyler-Lauren; Melendez, Caroline; Coller, Barry S

2015-04-01

Underenrollment of clinical studies wastes resources and delays assessment of research discoveries. We describe the organization and impact of a centralized recruitment core delivering comprehensive recruitment support to investigators. The Rockefeller University Center for Clinical and Translational Science supports a centralized recruitment core, call center, Research Volunteer Repository, data infrastructure, and staff who provide expert recruitment services to investigators. During protocol development, consultations aim to optimize enrollment feasibility, develop recruitment strategy, budget, and advertising. Services during study conduct include advertising placement, repository queries, call management, prescreening, referral, and visit scheduling. Utilization and recruitment outcomes are tracked using dedicated software. For protocols receiving recruitment services during 2009-2013: median time from initiation of recruitment to the first enrolled participant was 10 days; of 4,047 first-time callers to the call center, 92% (n = 3,722) enrolled in the Research Volunteer Repository, with 99% retention; 23% of Repository enrollees subsequently enrolled in ≥1 research studies, with 89% retention. Of volunteers referred by repository queries, 49% (280/537) enrolled into the study, with 92% retained. Provision of robust recruitment infrastructure including expertise, a volunteer repository, data capture and real-time analysis accelerates protocol accrual. Application of recruitment science improves the quality of clinical investigation. © 2014 Wiley Periodicals, Inc.

A Data‐Rich Recruitment Core to Support Translational Clinical Research

PubMed Central

Corregano, Lauren M.; Rainer, Tyler‐Lauren; Melendez, Caroline; Coller, Barry S.

2014-01-01

Abstract Background Underenrollment of clinical studies wastes resources and delays assessment of research discoveries. We describe the organization and impact of a centralized recruitment core delivering comprehensive recruitment support to investigators. Methods The Rockefeller University Center for Clinical and Translational Science supports a centralized recruitment core, call center, Research Volunteer Repository, data infrastructure, and staff who provide expert recruitment services to investigators. During protocol development, consultations aim to optimize enrollment feasibility, develop recruitment strategy, budget, and advertising. Services during study conduct include advertising placement, repository queries, call management, prescreening, referral, and visit scheduling. Utilization and recruitment outcomes are tracked using dedicated software. Results For protocols receiving recruitment services during 2009–2013: median time from initiation of recruitment to the first enrolled participant was 10 days; of 4,047 first‐time callers to the call center, 92% (n = 3,722) enrolled in the Research Volunteer Repository, with 99% retention; 23% of Repository enrollees subsequently enrolled in ≥1 research studies, with 89% retention. Of volunteers referred by repository queries, 49% (280/537) enrolled into the study, with 92% retained. Conclusions Provision of robust recruitment infrastructure including expertise, a volunteer repository, data capture and real‐time analysis accelerates protocol accrual. Application of recruitment science improves the quality of clinical investigation. PMID:25381717

NeuPAT: an intranet database supporting translational research in neuroblastic tumors.

PubMed

Villamón, Eva; Piqueras, Marta; Meseguer, Javier; Blanquer, Ignacio; Berbegall, Ana P; Tadeo, Irene; Hernández, Vicente; Navarro, Samuel; Noguera, Rosa

2013-03-01

Translational research in oncology is directed mainly towards establishing a better risk stratification and searching for appropriate therapeutic targets. This research generates a tremendous amount of complex clinical and biological data needing speedy and effective management. The authors describe the design, implementation and early experiences of a computer-aided system for the integration and management of data for neuroblastoma patients. NeuPAT facilitates clinical and translational research, minimizes the workload in consolidating the information, reduces errors and increases correlation of data through extensive coding. This design can also be applied to other tumor types. Copyright © 2012 Elsevier Ltd. All rights reserved.

Pharmacogenomics in early-phase clinical development

PubMed Central

Burt, Tal; Dhillon, Savita

2015-01-01

Pharmacogenomics (PGx) offers the promise of utilizing genetic fingerprints to predict individual responses to drugs in terms of safety, efficacy and pharmacokinetics. Early-phase clinical trial PGx applications can identify human genome variations that are meaningful to study design, selection of participants, allocation of resources and clinical research ethics. Results can inform later-phase study design and pipeline developmental decisions. Nevertheless, our review of the clinicaltrials.gov database demonstrates that PGx is rarely used by drug developers. Of the total 323 trials that included PGx as an outcome, 80% have been conducted by academic institutions after initial regulatory approval. Barriers for the application of PGx are discussed. We propose a framework for the role of PGx in early-phase drug development and recommend PGx be universally considered in study design, result interpretation and hypothesis generation for later-phase studies, but PGx results from underpowered studies should not be used by themselves to terminate drug-development programs. PMID:23837482

Design, clinical translation and immunological response of biomaterials in regenerative medicine

NASA Astrophysics Data System (ADS)

Sadtler, Kaitlyn; Singh, Anirudha; Wolf, Matthew T.; Wang, Xiaokun; Pardoll, Drew M.; Elisseeff, Jennifer H.

2016-07-01

The field of regenerative medicine aims to replace tissues lost as a consequence of disease, trauma or congenital abnormalities. Biomaterials serve as scaffolds for regenerative medicine to deliver cells, provide biological signals and physical support, and mobilize endogenous cells to repair tissues. Sophisticated chemistries are used to synthesize materials that mimic and modulate native tissue microenvironments, to replace form and to elucidate structure-function relationships of cell-material interactions. The therapeutic relevance of these biomaterial properties can only be studied after clinical translation, whereby key parameters for efficacy can be defined and then used for future design. In this Review, we present the development and translation of biomaterials for two tissue engineering targets, cartilage and cornea, both of which lack the ability to self-repair. Finally, looking to the future, we discuss the role of the immune system in regeneration and the potential for biomaterial scaffolds to modulate immune signalling to create a pro-regenerative environment.

One Size Will Never Fit All: Clinical and Translational Research Gaps in Pediatric Transfusion Medicine

PubMed Central

Josephson, Cassandra D.; Mondoro, Traci Heath; Ambruso, Daniel R.; Sanchez, Rosa; Sloan, Steven R.; Luban, Naomi L.C.; Widness, John A.

2015-01-01

There is concern at the National Heart, Lung, and Blood Institute (NHLBI) and among transfusion medicine specialists regarding the small number of investigators and studies in the field of pediatric transfusion medicine (PTM). Accordingly, the objective of this article is to provide a snapshot of the clinical and translational PTM research considered to be of high priority by pediatricians, neonatologists, and transfusion medicine specialists. Included is a targeted review of three research areas of importance: 1) transfusion strategies, 2) short- and long-term clinical consequences, and 3) transfusion-transmitted infectious diseases. The recommendations by PTM and transfusion medicine specialists represent opportunities and innovative strategies to execute translational research, observational studies, and clinical trials of high relevance to PTM. With the explosion of new biomedical knowledge and increasingly sophisticated methodologies over the past decade, this is an exciting time to consider transfusion medicine as a paradigm for addressing questions related to fields such as cell biology, immunology, neurodevelopment, outcomes research and many others. Increased awareness of PTM as an, important, fertile field and the promotion of accompanying opportunities will help establish PTM as a viable career option and advance basic and clinical investigation to improve the health and wellbeing of children. PMID:25119336

Translating Evidence Into Practice via Social Media: A Mixed-Methods Study

PubMed Central

Tunnecliff, Jacqueline; Morgan, Prue; Gaida, Jamie E; Clearihan, Lyn; Sadasivan, Sivalal; Davies, David; Ganesh, Shankar; Mohanty, Patitapaban; Weiner, John; Reynolds, John; Ilic, Dragan

2015-01-01

Background Approximately 80% of research evidence relevant to clinical practice never reaches the clinicians delivering patient care. A key barrier for the translation of evidence into practice is the limited time and skills clinicians have to find and appraise emerging evidence. Social media may provide a bridge between health researchers and health service providers. Objective The aim of this study was to determine the efficacy of social media as an educational medium to effectively translate emerging research evidence into clinical practice. Methods The study used a mixed-methods approach. Evidence-based practice points were delivered via social media platforms. The primary outcomes of attitude, knowledge, and behavior change were assessed using a preintervention/postintervention evaluation, with qualitative data gathered to contextualize the findings. Results Data were obtained from 317 clinicians from multiple health disciplines, predominantly from the United Kingdom, Australia, the United States, India, and Malaysia. The participants reported an overall improvement in attitudes toward social media for professional development (P<.001). The knowledge evaluation demonstrated a significant increase in knowledge after the training (P<.001). The majority of respondents (136/194, 70.1%) indicated that the education they had received via social media had changed the way they practice, or intended to practice. Similarly, a large proportion of respondents (135/193, 69.9%) indicated that the education they had received via social media had increased their use of research evidence within their clinical practice. Conclusions Social media may be an effective educational medium for improving knowledge of health professionals, fostering their use of research evidence, and changing their clinical behaviors by translating new research evidence into clinical practice. PMID:26503129

Translating Evidence Into Practice via Social Media: A Mixed-Methods Study.

PubMed

Maloney, Stephen; Tunnecliff, Jacqueline; Morgan, Prue; Gaida, Jamie E; Clearihan, Lyn; Sadasivan, Sivalal; Davies, David; Ganesh, Shankar; Mohanty, Patitapaban; Weiner, John; Reynolds, John; Ilic, Dragan

2015-10-26

Approximately 80% of research evidence relevant to clinical practice never reaches the clinicians delivering patient care. A key barrier for the translation of evidence into practice is the limited time and skills clinicians have to find and appraise emerging evidence. Social media may provide a bridge between health researchers and health service providers. The aim of this study was to determine the efficacy of social media as an educational medium to effectively translate emerging research evidence into clinical practice. The study used a mixed-methods approach. Evidence-based practice points were delivered via social media platforms. The primary outcomes of attitude, knowledge, and behavior change were assessed using a preintervention/postintervention evaluation, with qualitative data gathered to contextualize the findings. Data were obtained from 317 clinicians from multiple health disciplines, predominantly from the United Kingdom, Australia, the United States, India, and Malaysia. The participants reported an overall improvement in attitudes toward social media for professional development (P<.001). The knowledge evaluation demonstrated a significant increase in knowledge after the training (P<.001). The majority of respondents (136/194, 70.1%) indicated that the education they had received via social media had changed the way they practice, or intended to practice. Similarly, a large proportion of respondents (135/193, 69.9%) indicated that the education they had received via social media had increased their use of research evidence within their clinical practice. Social media may be an effective educational medium for improving knowledge of health professionals, fostering their use of research evidence, and changing their clinical behaviors by translating new research evidence into clinical practice.

Application of statistical machine translation to public health information: a feasibility study

PubMed Central

Turner, Anne M; Axelrod, Amittai; Saavedra, Francisco

2011-01-01

Objective Accurate, understandable public health information is important for ensuring the health of the nation. The large portion of the US population with Limited English Proficiency is best served by translations of public-health information into other languages. However, a large number of health departments and primary care clinics face significant barriers to fulfilling federal mandates to provide multilingual materials to Limited English Proficiency individuals. This article presents a pilot study on the feasibility of using freely available statistical machine translation technology to translate health promotion materials. Design The authors gathered health-promotion materials in English from local and national public-health websites. Spanish versions were created by translating the documents using a freely available machine-translation website. Translations were rated for adequacy and fluency, analyzed for errors, manually corrected by a human posteditor, and compared with exclusively manual translations. Results Machine translation plus postediting took 15–53 min per document, compared to the reported days or even weeks for the standard translation process. A blind comparison of machine-assisted and human translations of six documents revealed overall equivalency between machine-translated and manually translated materials. The analysis of translation errors indicated that the most important errors were word-sense errors. Conclusion The results indicate that machine translation plus postediting may be an effective method of producing multilingual health materials with equivalent quality but lower cost compared to manual translations. PMID:21498805

Word reading and translation in bilinguals: the impact of formal and informal translation expertise

PubMed Central

García, Adolfo M.; Ibáñez, Agustín; Huepe, David; Houck, Alexander L.; Michon, Maëva; Lezama, Carlos G.; Chadha, Sumeer; Rivera-Rei, Álvaro

2014-01-01

Studies on bilingual word reading and translation have examined the effects of lexical variables (e.g., concreteness, cognate status) by comparing groups of non-translators with varying levels of L2 proficiency. However, little attention has been paid to another relevant factor: translation expertise (TI). To explore this issue, we administered word reading and translation tasks to two groups of non-translators possessing different levels of informal TI (Experiment 1), and to three groups of bilinguals possessing different levels of translation training (Experiment 2). Reaction-time recordings showed that in all groups reading was faster than translation and unaffected by concreteness and cognate effects. Conversely, in both experiments, all groups translated concrete and cognate words faster than abstract and non-cognate words, respectively. Notably, an advantage of backward over forward translation was observed only for low-proficiency non-translators (in Experiment 1). Also, in Experiment 2, the modifications induced by translation expertise were more marked in the early than in the late stages of training and practice. The results suggest that TI contributes to modulating inter-equivalent connections in bilingual memory. PMID:25429279

75 FR 62543 - Proposed Collection; Comment Request; National Evaluation of the Clinical and Translational...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-12

... of the Clinical and Translational Science Awards (CTSA) Initiative SUMMARY: In compliance with the... comment on proposed data collection projects, the National Center for Research Resources (NCRR), the... National Evaluation of the Clinical and [[Page 62544

Bridging barriers to clinic-based HIV testing with new technology: translating self-implemented testing for African American youth.

PubMed

Catania, J A; Dolcini, M M; Harper, G W; Dowhower, D P; Dolcini-Catania, L G; Towner, S L; Timmons, A; Motley, D N; Tyler, D H

2015-12-01

Numerous barriers to clinic-based HIV testing exist (e.g., stigmatization) for African American youth. These barriers may be addressed by new technology, specifically HIV self-implemented testing (SIT). We conducted a series of formative phase 3 translation studies (49 face-to-face interviews, 9 focus groups, 1 advisory panel review) among low-income African American youth (15-19 years) and providers of adolescent services in two US cities to identify potential translation difficulties of the OraQuick SIT. Based on content analysis, we found that providers and African American youth viewed SITs positively compared to clinic-based testing. Data suggest that SITs may reduce social stigma and privacy concerns and increase convenience and normalization of HIV testing. Challenges with SIT implementation include difficulties accessing confirmatory testing, coping with adverse outcomes, and instructional materials that may be inappropriate for low socioeconomic status (SES) persons. Study results underscore the need for translation studies to identify specific comprehension and implementation problems African American youth may have with oral SITs.

Spanish translation and cross-language validation of a sleep habits questionnaire for use in clinical and research settings.

PubMed

Baldwin, Carol M; Choi, Myunghan; McClain, Darya Bonds; Celaya, Alma; Quan, Stuart F

2012-04-15

To translate, back-translate and cross-language validate (English/Spanish) the Sleep Heart Health Study Sleep Habits Questionnaire for use with Spanish-speakers in clinical and research settings. Following rigorous translation and back-translation, this cross-sectional cross-language validation study recruited bilingual participants from academic, clinic, and community-based settings (N = 50; 52% women; mean age 38.8 ± 12 years; 90% of Mexican heritage). Participants completed English and Spanish versions of the Sleep Habits Questionnaire, the Epworth Sleepiness Scale, and the Acculturation Rating Scale for Mexican Americans II one week apart in randomized order. Psychometric properties were assessed, including internal consistency, convergent validity, scale equivalence, language version intercorrelations, and exploratory factor analysis using PASW (Version18) software. Grade level readability of the sleep measure was evaluated. All sleep categories (duration, snoring, apnea, insomnia symptoms, other sleep symptoms, sleep disruptors, restless legs syndrome) showed Cronbach α, Spearman-Brown coefficients and intercorrelations ≥ 0.700, suggesting robust internal consistency, correlation, and agreement between language versions. The Epworth correlated significantly with snoring, apnea, sleep symptoms, restless legs, and sleep disruptors) on both versions, supporting convergent validity. Items loaded on 4 factors accounted for 68% and 67% of the variance on the English and Spanish versions, respectively. The Spanish-language Sleep Habits Questionnaire demonstrates conceptual and content equivalency. It has appropriate measurement properties and should be useful for assessing sleep health in community-based clinics and intervention studies among Spanish-speaking Mexican Americans. Both language versions showed readability at the fifth grade level. Further testing is needed with larger samples.

Uncovering the Rosetta Stone: Report from the First Annual Conference on Key Elements in Translating Stroke Therapeutics from Pre-Clinical to Clinical.

PubMed

Bix, Gregory J; Fraser, Justin F; Mack, William J; Carmichael, S Thomas; Perez-Pinzon, Miguel; Offner, Halina; Sansing, Lauren; Bosetti, Francesca; Ayata, Cenk; Pennypacker, Keith R

2018-06-01

The first annual Stroke Translational Research Advancement Workshop (STRAW), entitled "Uncovering the Rosetta Stone: Key Elements in Translating Stroke Therapeutics from Pre-Clinical to Clinical" was held at the University of Kentucky on October 4-5, 2017. This workshop was organized by the Center for Advanced Translational Stroke Science. The workshop consisted of 2 days of activities. These included three presentations establishing the areas of research in stroke therapeutics, discussing the routes for translation from bench to bedside, and identifying successes and failures in the field. On day 2, grant funding opportunities and goals for the National Institute for Neurological Diseases and Stroke were presented. In addition, the meeting also included break-out sessions designed to connect researchers in areas of stroke, and to foster potential collaborations. Finally, the meeting concluded with an open discussion among attendees led by a panel of experts.

How good is "evidence" from clinical studies of drug effects and why might such evidence fail in the prediction of the clinical utility of drugs?

PubMed

Naci, Huseyin; Ioannidis, John P A

2015-01-01

Promising evidence from clinical studies of drug effects does not always translate to improvements in patient outcomes. In this review, we discuss why early evidence is often ill suited to the task of predicting the clinical utility of drugs. The current gap between initially described drug effects and their subsequent clinical utility results from deficits in the design, conduct, analysis, reporting, and synthesis of clinical studies-often creating conditions that generate favorable, but ultimately incorrect, conclusions regarding drug effects. There are potential solutions that could improve the relevance of clinical evidence in predicting the real-world effectiveness of drugs. What is needed is a new emphasis on clinical utility, with nonconflicted entities playing a greater role in the generation, synthesis, and interpretation of clinical evidence. Clinical studies should adopt strong design features, reflect clinical practice, and evaluate outcomes and comparisons that are meaningful to patients. Transformative changes to the research agenda may generate more meaningful and accurate evidence on drug effects to guide clinical decision making.

Preparing clinical pharmacy scientists for careers in clinical/translational research: can we meet the challenge?: ACCP Research Affairs Committee Commentary.

PubMed

Parker, Robert B; Ellingrod, Vicki; DiPiro, Joseph T; Bauman, Jerry L; Blouin, Robert A; Welage, Lynda S

2013-12-01

Developing clinical pharmacists' research skills and their ability to compete for extramural funding is an important component of the American College of Clinical Pharmacy's (ACCP) vision for pharmacists to play a prominent role in generating the new knowledge used to guide patient pharmacotherapy. Given the recent emphasis on clinical/translational research at the National Institutes of Health (NIH) and the key role of drug therapy in the management of many diseases, there is an unprecedented opportunity for the profession to contribute to this enterprise. A crucial question facing the profession is whether we can generate enough appropriately trained scientists to take advantage of these opportunities to generate the new knowledge to advance drug therapy. Since the 2009 publication of the ACCP Research Affairs Committee editorial recommending the Ph.D. degree (as opposed to fellowship training) as the optimal method for preparing pharmacists as clinical/translational scientists, significant changes have occurred in the economic, professional, political, and research environments. As a result, the 2012 ACCP Research Affairs Committee was charged with reexamining the college's position on training clinical pharmacy scientists in the context of these substantial environmental changes. In this commentary, the potential impact of these changes on opportunities for pharmacists in clinical/translational research are discussed as are strategies for ACCP, colleges of pharmacy, and the profession to increase the number and impact of clinical pharmacy scientists. Failure of our profession to take advantage of these opportunities risks our ability to contribute substantively to the biomedical research enterprise and ultimately improve the pharmacotherapy of our patients. © 2013 Pharmacotherapy Publications, Inc.

Development of computer tablet software for clinical quantification of lateral knee compartment translation during the pivot shift test.

PubMed

Muller, Bart; Hofbauer, Marcus; Rahnemai-Azar, Amir Ata; Wolf, Megan; Araki, Daisuke; Hoshino, Yuichi; Araujo, Paulo; Debski, Richard E; Irrgang, James J; Fu, Freddie H; Musahl, Volker

2016-01-01

The pivot shift test is a commonly used clinical examination by orthopedic surgeons to evaluate knee function following injury. However, the test can only be graded subjectively by the examiner. Therefore, the purpose of this study is to develop software for a computer tablet to quantify anterior translation of the lateral knee compartment during the pivot shift test. Based on the simple image analysis method, software for a computer tablet was developed with the following primary design constraint - the software should be easy to use in a clinical setting and it should not slow down an outpatient visit. Translation of the lateral compartment of the intact knee was 2.0 ± 0.2 mm and for the anterior cruciate ligament-deficient knee was 8.9 ± 0.9 mm (p < 0.001). Intra-tester (ICC range = 0.913 to 0.999) and inter-tester (ICC = 0.949) reliability were excellent for the repeatability assessments. Overall, the average percent error of measuring simulated translation of the lateral knee compartment with the tablet parallel to the monitor increased from 2.8% at 50 cm distance to 7.7% at 200 cm. Deviation from the parallel position of the tablet did not have a significant effect until a tablet angle of 45°. Average percent error during anterior translation of the lateral knee compartment of 6mm was 2.2% compared to 6.2% for 2 mm of translation. The software provides reliable, objective, and quantitative data on translation of the lateral knee compartment during the pivot shift test and meets the design constraints posed by the clinical setting.

Sustaining the Clinical and Translational Research Workforce: Training and Empowering the Next Generation of Investigators.

PubMed

Yin, Helen L; Gabrilove, Janice; Jackson, Rebecca; Sweeney, Carol; Fair, Alecia M; Toto, Robert

2015-07-01

There is mounting concern that clinician-scientists are a vanishing species and that the pipeline for clinical and translational research (CTR) investigators is in jeopardy. For the majority of current junior CTR investigators, the career path involves first obtaining a National Institutes of Health (NIH)-funded K-type career development award, particularly K08 and K23, and subsequently an NIH R01. This transition, popularly referred to as K2R, is a major hurdle with a low success rate and gaps in funding. In this Perspective, the authors identify factors that facilitate K2R transition and important aspects of increasing and sustaining the pipeline of CTR investigators. They also highlight significant differences in success rates of women and those underrepresented in biomedical research. Early career exposure to research methodology, protected time, multidisciplinary mentoring, and institutional "culture shift" are important for fostering and rewarding team science. Mentoring is the single most important contributor to K2R success, and emerging evidence suggests that formal mentor training and team mentoring are effective. Leadership training can empower junior investigators to thrive as independent CTR investigators. Future research should focus on delineating the difference between essential and supplemental factors to achieve this transition, and mentoring methods that foster success, including those that promote K2R transition of women and those underrepresented in biomedical research. The Clinical and Translational Science Awards National Consortium is well positioned to test existing models aimed at shortening the time frame, increasing the rate of K2R transition, and identifying strategies that improve success.

Translational research to improve the treatment of severe extremity injuries.

PubMed

Brown, Kate V; Penn-Barwell, J G; Rand, B C; Wenke, J C

2014-06-01

Severe extremity injuries are the most significant injury sustained in combat wounds. Despite optimal clinical management, non-union and infection remain common complications. In a concerted effort to dovetail research efforts, there has been a collaboration between the UK and USA, with British military surgeons conducting translational studies under the auspices of the US Institute of Surgical Research. This paper describes 3 years of work. A variety of studies were conducted using, and developing, a previously validated rat femur critical-sized defect model. Timing of surgical debridement and irrigation, different types of irrigants and different means of delivery of antibiotic and growth factors for infection control and to promote bone healing were investigated. Early debridement and irrigation were independently shown to reduce infection. Normal saline was the most optimal irrigant, superior to disinfectant solutions. A biodegradable gel demonstrated superior antibiotic delivery capabilities than standard polymethylmethacrylate beads. A polyurethane scaffold was shown to have the ability to deliver both antibiotics and growth factors. The importance of early transit times to Role 3 capabilities for definitive surgical care has been underlined. Novel and superior methods of antibiotic and growth factor delivery, compared with current clinical standards of care, have been shown. There is the potential for translation to clinical studies to promote infection control and bone healing in these devastating injuries. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The Clinical Translation Gap in Child Health Exercise Research: A Call for Disruptive Innovation

PubMed Central

Ashish, Naveen; Bamman, Marcas M.; Cerny, Frank J.; D'Hemecourt, Pierre; Eisenmann, Joey C.; Ericson, Dawn; Fahey, John; Falk, Bareket; Gabriel, Davera; Kahn, Michael G.; Kemper, Han C.G.; Leu, Szu‐Yun; Liem, Robert I.; McMurray, Robert; Nixon, Patricia A.; Olin, J. Tod; Pianosi, Paolo T.; Purucker, Mary; Radom‐Aizik, Shlomit; Taylor, Amy

2014-01-01

Abstract In children, levels of play, physical activity, and fitness are key indicators of health and disease and closely tied to optimal growth and development. Cardiopulmonary exercise testing (CPET) provides clinicians with biomarkers of disease and effectiveness of therapy, and researchers with novel insights into fundamental biological mechanisms reflecting an integrated physiological response that is hidden when the child is at rest. Yet the growth of clinical trials utilizing CPET in pediatrics remains stunted despite the current emphasis on preventative medicine and the growing recognition that therapies used in children should be clinically tested in children. There exists a translational gap between basic discovery and clinical application in this essential component of child health. To address this gap, the NIH provided funding through the Clinical and Translational Science Award (CTSA) program to convene a panel of experts. This report summarizes our major findings and outlines next steps necessary to enhance child health exercise medicine translational research. We present specific plans to bolster data interoperability, improve child health CPET reference values, stimulate formal training in exercise medicine for child health care professionals, and outline innovative approaches through which exercise medicine can become more accessible and advance therapeutics across the broad spectrum of child health. PMID:25109386

The clinical translation gap in child health exercise research: a call for disruptive innovation.

PubMed

Ashish, Naveen; Bamman, Marcas M; Cerny, Frank J; Cooper, Dan M; D'Hemecourt, Pierre; Eisenmann, Joey C; Ericson, Dawn; Fahey, John; Falk, Bareket; Gabriel, Davera; Kahn, Michael G; Kemper, Han C G; Leu, Szu-Yun; Liem, Robert I; McMurray, Robert; Nixon, Patricia A; Olin, J Tod; Pianosi, Paolo T; Purucker, Mary; Radom-Aizik, Shlomit; Taylor, Amy

2015-02-01

In children, levels of play, physical activity, and fitness are key indicators of health and disease and closely tied to optimal growth and development. Cardiopulmonary exercise testing (CPET) provides clinicians with biomarkers of disease and effectiveness of therapy, and researchers with novel insights into fundamental biological mechanisms reflecting an integrated physiological response that is hidden when the child is at rest. Yet the growth of clinical trials utilizing CPET in pediatrics remains stunted despite the current emphasis on preventative medicine and the growing recognition that therapies used in children should be clinically tested in children. There exists a translational gap between basic discovery and clinical application in this essential component of child health. To address this gap, the NIH provided funding through the Clinical and Translational Science Award (CTSA) program to convene a panel of experts. This report summarizes our major findings and outlines next steps necessary to enhance child health exercise medicine translational research. We present specific plans to bolster data interoperability, improve child health CPET reference values, stimulate formal training in exercise medicine for child health care professionals, and outline innovative approaches through which exercise medicine can become more accessible and advance therapeutics across the broad spectrum of child health. © 2014 Wiley Periodicals, Inc.

Biomedical optics centers: forty years of multidisciplinary clinical translation for improving human health

NASA Astrophysics Data System (ADS)

Tromberg, Bruce J.; Anderson, R. Rox; Birngruber, Reginald; Brinkmann, Ralf; Berns, Michael W.; Parrish, John A.; Apiou-Sbirlea, Gabriela

2016-12-01

Despite widespread government and public interest, there are significant barriers to translating basic science discoveries into clinical practice. Biophotonics and biomedical optics technologies can be used to overcome many of these hurdles, due, in part, to offering new portable, bedside, and accessible devices. The current JBO special issue highlights promising activities and examples of translational biophotonics from leading laboratories around the world. We identify common essential features of successful clinical translation by examining the origins and activities of three major international academic affiliated centers with beginnings traceable to the mid-late 1970s: The Wellman Center for Photomedicine (Mass General Hospital, USA), the Beckman Laser Institute and Medical Clinic (University of California, Irvine, USA), and the Medical Laser Center Lübeck at the University of Lübeck, Germany. Major factors driving the success of these programs include visionary founders and leadership, multidisciplinary research and training activities in light-based therapies and diagnostics, diverse funding portfolios, and a thriving entrepreneurial culture that tolerates risk. We provide a brief review of how these three programs emerged and highlight critical phases and lessons learned. Based on these observations, we identify pathways for encouraging the growth and formation of similar programs in order to more rapidly and effectively expand the impact of biophotonics and biomedical optics on human health.

Biomedical optics centers: forty years of multidisciplinary clinical translation for improving human health.

PubMed

Tromberg, Bruce J; Anderson, R Rox; Birngruber, Reginald; Brinkmann, Ralf; Berns, Michael W; Parrish, John A; Apiou-Sbirlea, Gabriela

2016-12-01

Despite widespread government and public interest, there are significant barriers to translating basic science discoveries into clinical practice. Biophotonics and biomedical optics technologies can be used to overcome many of these hurdles, due, in part, to offering new portable, bedside, and accessible devices. The current JBO special issue highlights promising activities and examples of translational biophotonics from leading laboratories around the world. We identify common essential features of successful clinical translation by examining the origins and activities of three major international academic affiliated centers with beginnings traceable to the mid-late 1970s: The Wellman Center for Photomedicine (Mass General Hospital, USA), the Beckman Laser Institute and Medical Clinic (University of California, Irvine, USA), and the Medical Laser Center Lübeck at the University of Lübeck, Germany. Major factors driving the success of these programs include visionary founders and leadership, multidisciplinary research and training activities in light-based therapies and diagnostics, diverse funding portfolios, and a thriving entrepreneurial culture that tolerates risk. We provide a brief review of how these three programs emerged and highlight critical phases and lessons learned. Based on these observations, we identify pathways for encouraging the growth and formation of similar programs in order to more rapidly and effectively expand the impact of biophotonics and biomedical optics on human health.

[Early clinical trials in paediatric oncology in Spain: a nationwide perspective].

PubMed

Bautista, Francisco; Gallego, Soledad; Cañete, Adela; Mora, Jaume; Díaz de Heredia, Cristina; Cruz, Ofelia; Fernández, José María; Rives, Susana; Berlanga, Pablo; Hladun, Raquel; Juan Ribelles, Antonio; Madero, Luis; Ramírez, Manuel; Fernández Delgado, Rafael; Pérez-Martínez, Antonio; Mata, Cristina; Llort, Anna; Martín Broto, Javier; Cela, María Elena; Ramírez, Gema; Sábado, Constantino; Acha, Tomás; Astigarraga, Itziar; Sastre, Ana; Muñoz, Ascensión; Guibelalde, Mercedes; Moreno, Lucas

2017-09-01

Cancer is the leading cause of death between the first year of life and adolescence, and some types of diseases are still a major challenge in terms of cure. There is, therefore, a major need for new drugs. Recent findings in cancer biology open the door to the development of targeted therapies against individual molecular changes, as well as immunotherapy. Promising results in adult anti-cancer drug development have not yet been translated into paediatric clinical practice. A report is presented on the activity in early paediatric oncology trials (phase I-II) in Spain. All members of the Spanish Society of Paediatric Haematology Oncology (SEHOP) were contacted in order to identify early clinical trials in paediatric cancer opened between 2005 and 2015. A total of 30 trials had been opened in this period: 21 (70%) in solid tumours, and 9 (30%) in malignant haemopathies. A total of 212 patients have been enrolled. The majority was industry sponsored (53%). Since 2010, four centres have joined the international consortium of Innovative Therapies for Children with Cancer (ITCC), which has as its aim to develop novel therapies for paediatric tumours. A significant number of new studies have opened since 2010, improving the treatment opportunities for our children. Results of recently closed trials show the contribution of Spanish investigators, the introduction of molecularly targeted agents, and their benefits. The activity in clinical trials has increased in the years analysed. The SEHOP is committed to develop and participate in collaborative academic trials, in order to help in the advancement and optimisation of existing therapies in paediatric cancer. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Translational progress on tumor biomarkers

PubMed Central

Guo, Hongwei; Zhou, Xiaolin; Lu, Yi; Xie, Liye; Chen, Qian; Keller, Evan T; Liu, Qian; Zhou, Qinghua; Zhang, Jian

2015-01-01

There is an urgent need to apply basic research achievements to the clinic. In particular, mechanistic studies should be developed by bench researchers, depending upon clinical demands, in order to improve the survival and quality of life of cancer patients. To date, translational medicine has been addressed in cancer biology, particularly in the identification and characterization of novel tumor biomarkers. This review focuses on the recent achievements and clinical application prospects in tumor biomarkers based on translational medicine. PMID:26557902

From dental science to clinical practice: Knowledge translation and evidence-based dentistry principles.

PubMed

Afrashtehfar, Kelvin I; Assery, Mansour K

2017-07-01

It has been claimed that in order to decrease the gap between what we know and what we do, research findings must be translated from knowledge to action. Such practices better enable dentists to make evidence-based decisions instead of personal ideas and judgments. To this end, this literature review aims to revisit the concepts of knowledge translation and evidence-based dentistry (EBD) and depict their role and influence within dental education. It addresses some possible strategies to facilitate knowledge translation (KT), encourage dental students to use EBD principles, and to encourage dental educators to create an environment in which students become self-directed learners. It concludes with a call to develop up-to-date and efficient online platforms that could grant dentists better access to EBD sources in order to more efficiently translate research evidence into the clinic.

Preparation of near-infrared-labeled targeted contrast agents for clinical translation

NASA Astrophysics Data System (ADS)

Olive, D. Michael

2011-03-01

Targeted fluorophore-labeled contrast agents are moving toward translation to human surgical use. To prepare for future clinical use, we examined the performance of potential ligands targeting the epidermal growth factor receptor, α5β3 integrins, and GLUT transporters for their suitability as directed contrast agents. Each agent was labeled with IRDye 800CW, and near-infrared dye with excitation/emission wavelengths of 789/805 nm, which we determined had favorable toxicity characteristics. The probe molecules examined consisted of Affibodies, nanobodies, peptides, and the sugar 2-deoxy-D-glucose. Each probe was tested for specific and non-specific binding in cell based assays. All probe types showed good performance in mouse models for detecting either spontaneous tumors or tumor xenografts in vivo. Each of the probes tested show promise for future human clinical studies.

The Translational Science Training Program at NIH: Introducing Early Career Researchers to the Science and Operation of Translation of Basic Research to Medical Interventions

PubMed Central

Gilliland, C. Taylor; Sittampalam, G. Sitta; Wang, Philip Y.; Ryan, Philip E.

2016-01-01

Translational science is an emerging field that holds great promise to accelerate the development of novel medical interventions. As the field grows, so does the demand for highly trained biomedical scientists to fill the positions that are being created. Many graduate and postdoctorate training programs do not provide their trainees with sufficient education to take advantage of this growing employment sector. To help better prepare the trainees at the National Institutes of Health for possible careers in translation, we have created the Translational Science Training Program (TSTP)1. The TSTP is an intensive 2–3 day training program that introduces NIH postdoctoral trainees and graduate students to the science and operation of turning basic research discoveries into a medical therapeutic, device or diagnostic, and also exposes them to the variety of career options in translational science. Through a combination of classroom teaching from practicing experts in the various disciplines of translation and small group interactions with pre-clinical development teams, participants in the TSTP gain knowledge that will aid them in obtaining a career in translational science and building a network to make the transition to the field. PMID:27231204

Early vascular ageing in translation: from laboratory investigations to clinical applications in cardiovascular prevention.

PubMed

Nilsson, Peter M; Boutouyrie, Pierre; Cunha, Pedro; Kotsis, Vasilios; Narkiewicz, Krzysztof; Parati, Gianfranco; Rietzschel, Ernst; Scuteri, Angelo; Laurent, Stephane

2013-08-01

The ageing of the vascular tree is a fundamental reflection of biological ageing in general and a determinant of organ function. In the arterial wall this is characterized by a reduction in the elastin content, as well as by an increased content of collagen and its cross-linkages, leading to increased arterial stiffness and elevated central as well as brachial blood pressure, accompanied by increased SBP variability. In recent years a better understanding of these processes have led to the proposal of a condition named early vascular ageing (EVA) in patients with increased arterial stiffness for their age and sex. This is a condition that could increase cardiovascular risk and is associated with various degrees of cognitive dysfunction, as well as other features of biological ageing. This brief review aims to give an update on EVA and how the concept can be used in clinical practice.

The practical application of adaptive study design in early phase clinical trials: a retrospective analysis of time savings.

PubMed

Lorch, U; Berelowitz, K; Ozen, C; Naseem, A; Akuffo, E; Taubel, J

2012-05-01

The interest in adaptive study design is evident from the growing amount of clinical research employing this model in the mid to later stages of medicines development. Little has been published on the practical application and merits of adaptive study design in early phase clinical research. This paper describes a retrospective analysis performed on a sample of 29 industry lead adaptive early phase studies commencing between 1 January 2006 and 31 December 2010 in a clinical trials unit in London, England. All studies containing at least one adaptive feature in the original protocol were included in the analysis. The scope of the analysis was to assess whether the use of adaptive study designs provided tangible benefits over the use of conventional study designs using time savings as the main measure. We conclude that the use of adaptive study design saves time in early phase research programs. This is achieved by abolishing the need for substantial amendments or by mitigating their impact on timelines and by using adaptive scheduling efficiencies.

Translational physiology: from molecules to public health.

PubMed

Seals, Douglas R

2013-07-15

The term 'translational research' was coined 20 years ago and has become a guiding influence in biomedical research. It refers to a process by which the findings of basic research are extended to the clinical research setting (bench to bedside) and then to clinical practice and eventually health policy (bedside to community). It is a dynamic, multidisciplinary research approach. The concept of translational physiology applies the translational research model to the physiological sciences. It differs from the traditional areas of integrative and clinical physiology by its broad investigative scope of basic research to community health. Translational physiology offers exciting opportunities, but presently is under-developed and -utilized. A key challenge will be to expand physiological research by extending investigations to communities of patients and healthy (or at risk) individuals. This will allow bidirectional physiological investigation throughout the translational continuum: basic research observations can be studied up to the population level, and mechanisms can be assessed by 'reverse translation' in clinical research settings and preclinical models based on initial observations made in populations. Examples of translational physiology questions, experimental approaches, roadblocks and strategies for promotion are discussed. Translational physiology provides a novel framework for physiology programs and an investigational platform for physiologists to study function from molecular events to public health. It holds promise for enhancing the completeness and societal impact of our work, while further solidifying the critical role of physiology in the biomedical research enterprise.

Translation, adaptation, and validation of the Stanford Hypnotic Clinical Scale in Puerto Rico.

PubMed

Deynes-Exclusa, Yazmin; Sayers-Montalvo, Sean K; Martinez-Taboas, Alfonso

2011-04-01

The only hypnotizability scale that has been translated and validated for the Puerto Rican population is the Barber Suggestibility Scale (BSS). In this article, the Stanford Hypnotic Clinical Scale (SHCS) was translated and validated for this population. The translated SHCS ("Escala Stanford de Hipnosis Clinica" [ESHC]) was administered individually to 100 Puerto Rican college students. There were no significant differences found between the norms of the original SHCS samples and the Spanish version of the SHCS. Both samples showed similar distributions. The Spanish version's internal reliability as well as the item discrimination index were adequate. The authors conclude that the ESHC is an adequate instrument to measure hypnotizability in the Puerto Rican population.

Early childhood adversity, toxic stress, and the role of the pediatrician: translating developmental science into lifelong health.

PubMed

Garner, Andrew S; Shonkoff, Jack P

2012-01-01

Advances in a wide range of biological, behavioral, and social sciences are expanding our understanding of how early environmental influences (the ecology) and genetic predispositions (the biologic program) affect learning capacities, adaptive behaviors, lifelong physical and mental health, and adult productivity. A supporting technical report from the American Academy of Pediatrics (AAP) presents an integrated ecobiodevelopmental framework to assist in translating these dramatic advances in developmental science into improved health across the life span. Pediatricians are now armed with new information about the adverse effects of toxic stress on brain development, as well as a deeper understanding of the early life origins of many adult diseases. As trusted authorities in child health and development, pediatric providers must now complement the early identification of developmental concerns with a greater focus on those interventions and community investments that reduce external threats to healthy brain growth. To this end, AAP endorses a developing leadership role for the entire pediatric community-one that mobilizes the scientific expertise of both basic and clinical researchers, the family-centered care of the pediatric medical home, and the public influence of AAP and its state chapters-to catalyze fundamental change in early childhood policy and services. AAP is committed to leveraging science to inform the development of innovative strategies to reduce the precipitants of toxic stress in young children and to mitigate their negative effects on the course of development and health across the life span.

Exploring factors related to the translation of collaborative research learning experiences into clinical practice: Opportunities and tensions.

PubMed

Fletcher, Simon; Whiting, Cheryl; Boaz, Annette; Reeves, Scott

2017-07-01

Providing training opportunities to develop research skills for clinical staff has been prioritised in response to the need for improving the evidence base underpinning the delivery of care. By exploring the experiences of a number of former participants of a multidisciplinary postgraduate research course, this article explores the factors that have enabled and impeded staff to translate their learnt research skills into clinical practice. Adopting an exploratory case study approach, 16 interviews with 5 cohorts of Masters by Research in Clinical Practice (MResCP) graduates were undertaken. The interviews explored graduates' course experiences and their subsequent attempts to undertake clinical research. Analysis of the data indicated that although participants valued their interactions with colleagues from different professions and felt they gained useful research skills/knowledge, upon returning to clinical practice, they encountered a number of barriers which restricted their ability to apply their research expertise. Professional isolation, issues of hierarchy, and a lack of organisational support were key to limiting their ability to undertake clinical research. Further work is needed to explore in more depth how (i) these barriers can be overcome and (ii) how taught collaborative research skills can be more effectively translated into practice.

Stem Cell Research and Clinical Translation: A Roadmap about Good Clinical Practice and Patient Care.

PubMed

Frati, Paola; Scopetti, Matteo; Santurro, Alessandro; Gatto, Vittorio; Fineschi, Vittorio

2017-01-01

The latest research achievements in the field of stem cells led in 2016 to the publication of "Guidelines for Stem Cell Research and Clinical Translation" by the International Society for Stem Cell Research (ISSCR). Updating the topics covered in previous publications, the new recommendations offer interesting ethical and scientific insights. Under the common principles of research integrity, protection of patient's welfare, respect for the research subjects, transparency and social justice, the centrality of good clinical practice, and informed consent in research and translational medicine is supported. The guidelines implement the abovementioned publications, requiring rigor in all areas of research, promoting the validity of the scientific activity results and emphasizing the need for an accurate and efficient public communication. This paper aims to analyze the aforementioned guidelines in order to provide a valid interpretive tool for experts. In particular, a research activity focused on the bioethical, scientific, and social implications of the new recommendations is carried out in order to provide food for thought. Finally, as an emerging issue of potential impact of current guidelines, an overview on implications of compensation for egg donation is offered.

Detection and Evaluation of Early Breast Cancer via Magnetic Resonance Imaging: Studies of Mouse Models and Clinical Implementation

DTIC Science & Technology

2008-03-01

CONTRACT NUMBER Detection and Evaluation of Early Breast Cancer via Magnetic Resonance Imaging: Studies of Mouse Models and Clinical Implementation...research proposed here can directly lead to clinical improvements in both early breast cancer detection, as well as effective breast cancer therapy. To date... cancer is a major prognostic factor in the management of the disease. In particular, detecting breast cancer in its pre-invasive form as ductal carcinoma

Early career mentoring for translational researchers: mentee perspectives on challenges and issues.

PubMed

Keller, Thomas E; Collier, Peter J; Blakeslee, Jennifer E; Logan, Kay; McCracken, Karen; Morris, Cynthia

2014-01-01

The education and training of early career biomedical translational researchers often involves formal mentoring by more experienced colleagues. This study investigated the nature of these mentoring relationships from the perspective of mentees. The objective was to understand the challenges and issues encountered by mentees in forming and maintaining productive mentoring relationships. Three focus groups (n=14) were conducted with early career researchers who had mentored career development awards. Thematic analysis identified, categorized, and illustrated the challenges and issues reported by mentees. The range of mentee challenges was reflected in five major categories: (a) network--finding appropriate mentors to meet various needs; (b) access--structuring schedules and opportunities to receive mentoring; (c) expectations--negotiating the mechanics of the mentoring relationship and its purpose; (d) alignment--managing mentor-mentee mismatches regarding interests, priorities, and goals; and (e) skills and supports--developing the institutional supports to be successful. Mentoring relationships created for academic training and career development contend with tasks common to many other relationships, namely, recognizing compatibility, finding time, establishing patterns, agreeing to goals, and achieving aims. Identifying challenges faced by mentees can facilitate the development of appropriate trainings and supports to foster mentoring relationships in academic and career settings.

The translational science training program at NIH: Introducing early career researchers to the science and operation of translation of basic research to medical interventions.

PubMed

Gilliland, C Taylor; Sittampalam, G Sitta; Wang, Philip Y; Ryan, Philip E

2017-01-02

Translational science is an emerging field that holds great promise to accelerate the development of novel medical interventions. As the field grows, so does the demand for highly trained biomedical scientists to fill the positions that are being created. Many graduate and postdoctorate training programs do not provide their trainees with sufficient education to take advantage of this growing employment sector. To help better prepare the trainees at the National Institutes of Health for possible careers in translation, we have created the Translational Science Training Program (TSTP). The TSTP is an intensive 2- to 3-day training program that introduces NIH postdoctoral trainees and graduate students to the science and operation of turning basic research discoveries into a medical therapeutic, device or diagnostic, and also exposes them to the variety of career options in translational science. Through a combination of classroom teaching from practicing experts in the various disciplines of translation and small group interactions with pre-clinical development teams, participants in the TSTP gain knowledge that will aid them in obtaining a career in translational science and building a network to make the transition to the field. © 2016 by The International Union of Biochemistry and Molecular Biology, 45(1):13-24, 2017. © 2016 The International Union of Biochemistry and Molecular Biology.

FOCIS goes south: advances in translational and clinical immunology.

PubMed

Kalergis, Alexis M; Anegon, Ignacio; González, Pablo A

2017-09-01

FOCIS goes South: Advances in Translational and Clinical Immunology was the first Federation of Clinical Immunology Societies (FOCIS) ( www.focisnet.org ) meeting held in Latin America (May 15-17, 2017, Santiago de Chile, Chile). The meeting was organized as a 3-day workshop and was fostered by the Millennium Institute on Immunology and Immunotherapy, a recently nominated FOCIS Center of Excellence. The workshop brought together FOCIS associates, such as members of the FOCIS Board of Directors, Directors of different Centers of Excellence, regional speakers and 350 attendees. The Meeting covered aspects of immune regulation and modulation, as well as immunotherapy in areas of autoimmunity, transplantation, cancer and infectious diseases, among others. The activity also had a full-day immunology course and a day-long flow cytometry course.

Understanding Career Success and Its Contributing Factors for Clinical and Translational Investigators

PubMed Central

Robinson, Georgeanna F.W.B.; Schwartz, Lisa S.; DiMeglio, Linda A.; Ahluwalia, Jasjit S.; Gabrilove, Janice L.

2015-01-01

Purpose To understand the factors that facilitate career success for career development awardees in clinical and translational science and to reconceptualize understanding of career success for this population. Method In 2013–2014, the authors conducted semi-structured interviews with former NIH KL2 or K12 scholars from nine Clinical and Translational Science Award-funded institutions. Participants either had or had not secured independent funding at least two years after the end of their last K award. Questions covered the factors that facilitate or hinder junior investigators’ transition to independent funding. Interviews were recorded and transcribed and the transcripts analyzed thematically. Results Forty individuals participated, with equal representation by men and women and by independently and not independently funded investigators. Personal factors that facilitated success included: networks, persistence and resilience, initiative, autonomy, and personal and professional balance. Organizational factors included: appropriate mentorship, protected research time, and institutional resources and support. Even independently funded participants described challenges regarding career direction. Five participants without independent funding modeled a broad spectrum of successful career paths, having assumed leadership positions not reliant on grant funding. Alternative definitions of career success included: improving public health, enjoying work, seeing mentees succeed, and receiving external acknowledgement of successes. Conclusions Awareness of the factors that facilitate or hinder career success can help junior faculty, mentors, and institutional leaders support career development in clinical and translational science. New definitions of career success are needed, as are career paths for faculty who want to engage in research in roles other than principal investigator. PMID:26509600

Understanding Career Success and Its Contributing Factors for Clinical and Translational Investigators.

PubMed

Robinson, Georgeanna F W B; Schwartz, Lisa S; DiMeglio, Linda A; Ahluwalia, Jasjit S; Gabrilove, Janice L

2016-04-01

To understand the factors that facilitate career success for career development awardees in clinical and translational science and reconceptualize understand ing of career success for this population. In 2013-2014, the authors conducted semistructured interviews with former NIH KL2 or K12 scholars from nine Clinical and Translational Science Award-funded institutions. Participants either had or had not secured independent funding at least two years after the end of their last K award. Questions covered the factors that facilitate or hinder junior investigators' transition to independent funding. Interviews were recorded and transcribed, and the transcripts were analyzed thematically. Forty individuals participated, with equal representation by men and women and by independently and not independently funded investigators. Personal factors that facilitated success included networks, persistence and resilience, initiative, autonomy, and personal and professional balance. Organizational factors included appropriate mentorship, protected research time, and institutional resources and support.Even independently funded participants described challenges regarding career direction. Five participants without independent funding modeled a broad spectrum of successful career paths, having assumed leadership positions not reliant on grant funding. Alternative definitions of career success included improving public health, enjoying work, seeing mentees succeed, and receiving external acknowledgment of successes. Awareness of the factors that facilitate or hinder career success can help junior faculty, mentors, and institutional leaders support career development in clinical and translational science. New definitions of career success are needed, as are career paths for faculty who want to engage in research in roles other than principal investigator.

Computer-Aided Clinical Trial Recruitment Based on Domain-Specific Language Translation: A Case Study of Retinopathy of Prematurity

PubMed Central

2017-01-01

Reusing the data from healthcare information systems can effectively facilitate clinical trials (CTs). How to select candidate patients eligible for CT recruitment criteria is a central task. Related work either depends on DBA (database administrator) to convert the recruitment criteria to native SQL queries or involves the data mapping between a standard ontology/information model and individual data source schema. This paper proposes an alternative computer-aided CT recruitment paradigm, based on syntax translation between different DSLs (domain-specific languages). In this paradigm, the CT recruitment criteria are first formally represented as production rules. The referenced rule variables are all from the underlying database schema. Then the production rule is translated to an intermediate query-oriented DSL (e.g., LINQ). Finally, the intermediate DSL is directly mapped to native database queries (e.g., SQL) automated by ORM (object-relational mapping). PMID:29065644

Computer-Aided Clinical Trial Recruitment Based on Domain-Specific Language Translation: A Case Study of Retinopathy of Prematurity.

PubMed

Zhang, Yinsheng; Zhang, Guoming; Shang, Qian

2017-01-01

Reusing the data from healthcare information systems can effectively facilitate clinical trials (CTs). How to select candidate patients eligible for CT recruitment criteria is a central task. Related work either depends on DBA (database administrator) to convert the recruitment criteria to native SQL queries or involves the data mapping between a standard ontology/information model and individual data source schema. This paper proposes an alternative computer-aided CT recruitment paradigm, based on syntax translation between different DSLs (domain-specific languages). In this paradigm, the CT recruitment criteria are first formally represented as production rules. The referenced rule variables are all from the underlying database schema. Then the production rule is translated to an intermediate query-oriented DSL (e.g., LINQ). Finally, the intermediate DSL is directly mapped to native database queries (e.g., SQL) automated by ORM (object-relational mapping).

A Novel Clinically Translatable Fluorescent Nanoparticle for Targeted Molecular Imaging of Tumors in Living Subjects

PubMed Central

Gao, Jinhao; Chen, Kai; Luong, Richard; Bouley, Donna M.; Mao, Hua; Qiao, Tiecheng; Gambhir, Sanjiv S.; Cheng, Zhen

2011-01-01

The use of quantum dots (QDs) in biomedical research has grown tremendously, yet successful examples of clinical applications are absent due to many clinical concerns. Here, we report on a new type of stable and biocompatible dendron-coated InP/ZnS core/shell QDs as a clinically translatable nanoprobe for molecular imaging applications. The QDs (QD710-Dendron) were demonstrated to hold several significant features: near-infrared (NIR) emission, high stability in biological media, suitable size with possible renal clearance and ability of extravasation. More importantly, a pilot mouse toxicity study confirmed that QD710-Dendron lacks significant toxicity at the doses tested. The acute tumor uptake of QD710-Dendron resulted in good contrast from the surrounding non-tumorous tissues, indicating the possibility of passive targeting of the QDs. The highly specific targeting of QD710-Dendron-RGD2 to integrin αvβ3–positive tumor cells resulted in high tumor uptake and long retention of the nanoprobe at tumor sites. In summary, QD710-Dendron and RGD modified nanoparticles demonstrate small size, high stability, biocompatibility, favorable in vivo pharmacokinetics, and successful tumor imaging properties. These features satisfy the requirements for clinical translation and should promote efforts to further investigate the possibility of using QD710-Dendron based nanoprobes in the clinical setting in the near future. PMID:22172022

A novel clinically translatable fluorescent nanoparticle for targeted molecular imaging of tumors in living subjects.

PubMed

Gao, Jinhao; Chen, Kai; Luong, Richard; Bouley, Donna M; Mao, Hua; Qiao, Tiecheng; Gambhir, Sanjiv S; Cheng, Zhen

2012-01-11

The use of quantum dots (QDs) in biomedical research has grown tremendously, yet successful examples of clinical applications are absent due to many clinical concerns. Here, we report on a new type of stable and biocompatible dendron-coated InP/ZnS core/shell QD as a clinically translatable nanoprobe for molecular imaging applications. The QDs (QD710-Dendron) were demonstrated to hold several significant features: near-infrared (NIR) emission, high stability in biological media, suitable size with possible renal clearance, and ability of extravasation. More importantly, a pilot mouse toxicity study confirmed that QD710-Dendron lacks significant toxicity at the doses tested. The acute tumor uptake of QD710-Dendron resulted in good contrast from the surrounding nontumorous tissues, indicating the possibility of passive targeting of the QDs. The highly specific targeting of QD710-Dendron-RGD(2) to integrin α(v)β(3)-positive tumor cells resulted in high tumor uptake and long retention of the nanoprobe at tumor sites. In summary, QD710-Dendron and RGD-modified nanoparticles demonstrate small size, high stability, biocompatibility, favorable in vivo pharmacokinetics, and successful tumor imaging properties. These features satisfy the requirements for clinical translation and should promote efforts to further investigate the possibility of using QD710-Dendron-based nanoprobes in the clinical setting in the near future. © 2011 American Chemical Society

Enhanced transcription and translation in clay hydrogel and implications for early life evolution

PubMed Central

Yang, Dayong; Peng, Songming; Hartman, Mark R.; Gupton-Campolongo, Tiffany; Rice, Edward J.; Chang, Anna Kathryn; Gu, Zi; Lu, G. Q. (Max); Luo, Dan

2013-01-01

In most contemporary life forms, the confinement of cell membranes provides localized concentration and protection for biomolecules, leading to efficient biochemical reactions. Similarly, confinement may have also played an important role for prebiotic compartmentalization in early life evolution when the cell membrane had not yet formed. It remains an open question how biochemical reactions developed without the confinement of cell membranes. Here we mimic the confinement function of cells by creating a hydrogel made from geological clay minerals, which provides an efficient confinement environment for biomolecules. We also show that nucleic acids were concentrated in the clay hydrogel and were protected against nuclease, and that transcription and translation reactions were consistently enhanced. Taken together, our results support the importance of localized concentration and protection of biomolecules in early life evolution, and also implicate a clay hydrogel environment for biochemical reactions during early life evolution. PMID:24196527

Systematic reviews of animal studies; missing link in translational research?

PubMed

van Luijk, Judith; Bakker, Brenda; Rovers, Maroeska M; Ritskes-Hoitinga, Merel; de Vries, Rob B M; Leenaars, Marlies

2014-01-01

The methodological quality of animal studies is an important factor hampering the translation of results from animal studies to a clinical setting. Systematic reviews of animal studies may provide a suitable method to assess and thereby improve their methodological quality. The aims of this study were: 1) to evaluate the risk of bias assessment in animal-based systematic reviews, and 2) to study the internal validity of the primary animal studies included in these systematic reviews. We systematically searched Pubmed and Embase for SRs of preclinical animal studies published between 2005 and 2012. A total of 91 systematic reviews met our inclusion criteria. The risk of bias was assessed in 48 (52.7%) of these 91 systematic reviews. Thirty-three (36.3%) SRs provided sufficient information to evaluate the internal validity of the included studies. Of the evaluated primary studies, 24.6% was randomized, 14.6% reported blinding of the investigator/caretaker, 23.9% blinded the outcome assessment, and 23.1% reported drop-outs. To improve the translation of animal data to clinical practice, systematic reviews of animal studies are worthwhile, but the internal validity of primary animal studies needs to be improved. Furthermore, risk of bias should be assessed by systematic reviews of animal studies to provide insight into the reliability of the available evidence.

Translational physiology: from molecules to public health

PubMed Central

Seals, Douglas R

2013-01-01

The term ‘translational research’ was coined 20 years ago and has become a guiding influence in biomedical research. It refers to a process by which the findings of basic research are extended to the clinical research setting (bench to bedside) and then to clinical practice and eventually health policy (bedside to community). It is a dynamic, multidisciplinary research approach. The concept of translational physiology applies the translational research model to the physiological sciences. It differs from the traditional areas of integrative and clinical physiology by its broad investigative scope of basic research to community health. Translational physiology offers exciting opportunities, but presently is under-developed and -utilized. A key challenge will be to expand physiological research by extending investigations to communities of patients and healthy (or at risk) individuals. This will allow bidirectional physiological investigation throughout the translational continuum: basic research observations can be studied up to the population level, and mechanisms can be assessed by ‘reverse translation’ in clinical research settings and preclinical models based on initial observations made in populations. Examples of translational physiology questions, experimental approaches, roadblocks and strategies for promotion are discussed. Translational physiology provides a novel framework for physiology programs and an investigational platform for physiologists to study function from molecular events to public health. It holds promise for enhancing the completeness and societal impact of our work, while further solidifying the critical role of physiology in the biomedical research enterprise. PMID:23732641

Understanding factors associated with the translation of cardiovascular research: a multinational case study approach

PubMed Central

2014-01-01

Background Funders of health research increasingly seek to understand how best to allocate resources in order to achieve maximum value from their funding. We built an international consortium and developed a multinational case study approach to assess benefits arising from health research. We used that to facilitate analysis of factors in the production of research that might be associated with translating research findings into wider impacts, and the complexities involved. Methods We built on the Payback Framework and expanded its application through conducting co-ordinated case studies on the payback from cardiovascular and stroke research in Australia, Canada and the United Kingdom. We selected a stratified random sample of projects from leading medical research funders. We devised a series of innovative steps to: minimize the effect of researcher bias; rate the level of impacts identified in the case studies; and interrogate case study narratives to identify factors that correlated with achieving high or low levels of impact. Results Twenty-nine detailed case studies produced many and diverse impacts. Over the 15 to 20 years examined, basic biomedical research has a greater impact than clinical research in terms of academic impacts such as knowledge production and research capacity building. Clinical research has greater levels of wider impact on health policies, practice, and generating health gains. There was no correlation between knowledge production and wider impacts. We identified various factors associated with high impact. Interaction between researchers and practitioners and the public is associated with achieving high academic impact and translation into wider impacts, as is basic research conducted with a clinical focus. Strategic thinking by clinical researchers, in terms of thinking through pathways by which research could potentially be translated into practice, is associated with high wider impact. Finally, we identified the complexity of

Understanding factors associated with the translation of cardiovascular research: a multinational case study approach.

PubMed

Wooding, Steven; Hanney, Stephen R; Pollitt, Alexandra; Grant, Jonathan; Buxton, Martin J

2014-04-21

Funders of health research increasingly seek to understand how best to allocate resources in order to achieve maximum value from their funding. We built an international consortium and developed a multinational case study approach to assess benefits arising from health research. We used that to facilitate analysis of factors in the production of research that might be associated with translating research findings into wider impacts, and the complexities involved. We built on the Payback Framework and expanded its application through conducting co-ordinated case studies on the payback from cardiovascular and stroke research in Australia, Canada and the United Kingdom. We selected a stratified random sample of projects from leading medical research funders. We devised a series of innovative steps to: minimize the effect of researcher bias; rate the level of impacts identified in the case studies; and interrogate case study narratives to identify factors that correlated with achieving high or low levels of impact. Twenty-nine detailed case studies produced many and diverse impacts. Over the 15 to 20 years examined, basic biomedical research has a greater impact than clinical research in terms of academic impacts such as knowledge production and research capacity building. Clinical research has greater levels of wider impact on health policies, practice, and generating health gains. There was no correlation between knowledge production and wider impacts. We identified various factors associated with high impact. Interaction between researchers and practitioners and the public is associated with achieving high academic impact and translation into wider impacts, as is basic research conducted with a clinical focus. Strategic thinking by clinical researchers, in terms of thinking through pathways by which research could potentially be translated into practice, is associated with high wider impact. Finally, we identified the complexity of factors behind research

Pre-clinical research in small animals using radiotherapy technology--a bidirectional translational approach.

PubMed

Tillner, Falk; Thute, Prasad; Bütof, Rebecca; Krause, Mechthild; Enghardt, Wolfgang

2014-12-01

For translational cancer research, pre-clinical in-vivo studies using small animals have become indispensable in bridging the gap between in-vitro cell experiments and clinical implementation. When setting up such small animal experiments, various biological, technical and methodical aspects have to be considered. In this work we present a comprehensive topical review based on relevant publications on irradiation techniques used for pre-clinical cancer research in mice and rats. Clinical radiotherapy treatment devices for the application of external beam radiotherapy and brachytherapy as well as dedicated research irradiation devices are feasible for small animal irradiation depending on the animal model and the experimental goals. In this work, appropriate solutions for the technological transfer of human radiation oncology to small animal radiation research are summarised. Additionally, important information concerning the experimental design is provided such that reliable and clinically relevant results can be attained. Copyright © 2014. Published by Elsevier GmbH.

Landscape of early clinical trials for childhood and adolescence cancer in Spain.

PubMed

Bautista, F; Gallego, S; Cañete, A; Mora, J; Diaz de Heredia, C; Cruz, O; Fernández, J M; Rives, S; Madero, L; Castel, V; Cela, M E; Ramírez, G; Sábado, C; Acha, T; Astigarraga, I; Sastre, A; Muñoz, A; Guibelalde, M; Moreno, L

2016-07-01

Despite numerous advances, survival remains dismal for children and adolescents with poor prognosis cancers or those who relapse or are refractory to first line treatment. There is, therefore, a major unmet need for new drugs. Recent advances in the knowledge of molecular tumor biology open the door to more adapted therapies according to individual alterations. Promising results in the adult anticancer drug development have not yet been translated into clinical practice. We report the activity in early pediatric oncology trials in Spain. All members of the Spanish Society of Pediatric Hematology Oncology (SEHOP) were contacted to obtain information about early trials open in each center. 22 phase I and II trials were open as of May 2015: 15 for solid tumors (68 %) and 7 for hematological malignancies (32 %). Fourteen (64 %) were industry sponsored. Since 2010, four centers have joined the Innovative Therapies For Children With Cancer, an international consortium whose aim is developing novel therapies for pediatric cancers. A substantial number of studies have opened in these 5 years, improving the portfolio of trials for children. Results of recently closed trials show the contribution of Spanish investigators, the introduction of molecularly targeted agents and their benefits. Clinical trials are the way to evaluate new drugs, avoiding the use of off-label drugs that carry significant risks. The Spanish pediatric oncology community through the SEHOP is committed to develop and participate in collaborative academic trials, to favor the advancement and optimization of existing therapies in pediatric cancer.

Personalized translational epilepsy research - Novel approaches and future perspectives: Part I: Clinical and network analysis approaches.

PubMed

Rosenow, Felix; van Alphen, Natascha; Becker, Albert; Chiocchetti, Andreas; Deichmann, Ralf; Deller, Thomas; Freiman, Thomas; Freitag, Christine M; Gehrig, Johannes; Hermsen, Anke M; Jedlicka, Peter; Kell, Christian; Klein, Karl Martin; Knake, Susanne; Kullmann, Dimitri M; Liebner, Stefan; Norwood, Braxton A; Omigie, Diana; Plate, Karlheinz; Reif, Andreas; Reif, Philipp S; Reiss, Yvonne; Roeper, Jochen; Ronellenfitsch, Michael W; Schorge, Stephanie; Schratt, Gerhard; Schwarzacher, Stephan W; Steinbach, Joachim P; Strzelczyk, Adam; Triesch, Jochen; Wagner, Marlies; Walker, Matthew C; von Wegner, Frederic; Bauer, Sebastian

2017-11-01

Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been identified to date. This is likely in part due to the polyetiologic nature of epilepsy, which in turn requires personalized medicine approaches. Recent advances in imaging, pathology, genetics and epigenetics have led to new pathophysiological concepts and the identification of monogenic causes of epilepsy. In the context of these advances, the First International Symposium on Personalized Translational Epilepsy Research (1st ISymPTER) was held in Frankfurt on September 8, 2016, to discuss novel approaches and future perspectives for personalized translational research. These included new developments and ideas in a range of experimental and clinical areas such as deep phenotyping, quantitative brain imaging, EEG/MEG-based analysis of network dysfunction, tissue-based translational studies, innate immunity mechanisms, microRNA as treatment targets, functional characterization of genetic variants in human cell models and rodent organotypic slice cultures, personalized treatment approaches for monogenic epilepsies, blood-brain barrier dysfunction, therapeutic focal tissue modification, computational modeling for target and biomarker identification, and cost analysis in (monogenic) disease and its treatment. This report on the meeting proceedings is aimed at stimulating much needed investments of time and resources in personalized translational epilepsy research. Part I includes the clinical phenotyping and diagnostic methods, EEG network-analysis, biomarkers, and personalized treatment approaches. In Part II, experimental and translational approaches will be discussed (Bauer et al., 2017) [1]. Copyright © 2017 Elsevier Inc

Computational neurobiology is a useful tool in translational neurology: the example of ataxia

PubMed Central

Brown, Sherry-Ann; McCullough, Louise D.; Loew, Leslie M.

2014-01-01

Hereditary ataxia, or motor incoordination, affects approximately 150,000 Americans and hundreds of thousands of individuals worldwide with onset from as early as mid-childhood. Affected individuals exhibit dysarthria, dysmetria, action tremor, and diadochokinesia. In this review, we consider an array of computational studies derived from experimental observations relevant to human neuropathology. A survey of related studies illustrates the impact of integrating clinical evidence with data from mouse models and computational simulations. Results from these studies may help explain findings in mice, and after extensive laboratory study, may ultimately be translated to ataxic individuals. This inquiry lays a foundation for using computation to understand neurobiochemical and electrophysiological pathophysiology of spinocerebellar ataxias and may contribute to development of therapeutics. The interdisciplinary analysis suggests that computational neurobiology can be an important tool for translational neurology. PMID:25653585

Pre-clinical Safety and Off-Target Studies to Support Translation of AAV-Mediated RNAi Therapy for FSHD.

PubMed

Wallace, Lindsay M; Saad, Nizar Y; Pyne, Nettie K; Fowler, Allison M; Eidahl, Jocelyn O; Domire, Jacqueline S; Griffin, Danielle A; Herman, Adam C; Sahenk, Zarife; Rodino-Klapac, Louise R; Harper, Scott Q

2018-03-16

RNAi emerged as a prospective molecular therapy nearly 15 years ago. Since then, two major RNAi platforms have been under development: oligonucleotides and gene therapy. Oligonucleotide-based approaches have seen more advancement, with some promising therapies that may soon reach market. In contrast, vector-based approaches for RNAi therapy have remained largely in the pre-clinical realm, with limited clinical safety and efficacy data to date. We are developing a gene therapy approach to treat the autosomal-dominant disorder facioscapulohumeral muscular dystrophy. Our strategy involves silencing the myotoxic gene DUX4 using adeno-associated viral vectors to deliver targeted microRNA expression cassettes (miDUX4s). We previously demonstrated proof of concept for this approach in mice, and we are now taking additional steps here to assess safety issues related to miDUX4 overexpression and sequence-specific off-target silencing. In this study, we describe improvements in vector design and expansion of our miDUX4 sequence repertoire and report differential toxicity elicited by two miDUX4 sequences, of which one was toxic and the other was not. This study provides important data to help advance our goal of translating RNAi gene therapy for facioscapulohumeral muscular dystrophy.

A research mentor training curriculum for clinical and translational researchers.

PubMed

Pfund, Christine; House, Stephanie; Spencer, Kimberly; Asquith, Pamela; Carney, Paula; Masters, Kristyn S; McGee, Richard; Shanedling, Janet; Vecchiarelli, Stephanie; Fleming, Michael

2013-02-01

To design and evaluate a research mentor training curriculum for clinical and translational researchers. The resulting 8-hour curriculum was implemented as part of a national mentor training trial. The mentor training curriculum was implemented with 144 mentors at 16 academic institutions. Facilitators of the curriculum participated in a train-the-trainer workshop to ensure uniform delivery. The data used for this report were collected from participants during the training sessions through reflective writing, and following the last training session via confidential survey with a 94% response rate. A total of 88% of respondents reported high levels of satisfaction with the training experience, and 90% noted they would recommend the training to a colleague. Participants also reported significant learning gains across six mentoring competencies as well as specific impacts of the training on their mentoring practice. The data suggest the described research mentor training curriculum is an effective means of engaging research mentors to reflect upon and improve their research mentoring practices. The training resulted in high satisfaction, self-reported skill gains as well as behavioral changes of clinical and translational research mentors. Given success across 16 diverse sites, this training may serve as a national model. © 2012 Wiley Periodicals, Inc.

A Research Mentor Training Curriculum for Clinical and Translational Researchers

PubMed Central

House, Stephanie; Spencer, Kimberly; Asquith, Pamela; Carney, Paula; Masters, Kristyn S.; McGee, Richard; Shanedling, Janet; Vecchiarelli, Stephanie; Fleming, Michael

2012-01-01

Abstract Purpose To design and evaluate a research mentor training curriculum for clinical and translational researchers. The resulting 8‐hour curriculum was implemented as part of a national mentor training trial. Method The mentor training curriculum was implemented with 144 mentors at 16 academic institutions. Facilitators of the curriculum participated in a train‐the‐trainer workshop to ensure uniform delivery. The data used for this report were collected from participants during the training sessions through reflective writing, and following the last training session via confidential survey with a 94% response rate. Results A total of 88% of respondents reported high levels of satisfaction with the training experience, and 90% noted they would recommend the training to a colleague. Participants also reported significant learning gains across six mentoring competencies as well as specific impacts of the training on their mentoring practice. Conclusions The data suggest the described research mentor training curriculum is an effective means of engaging research mentors to reflect upon and improve their research mentoring practices. The training resulted in high satisfaction, self‐reported skill gains as well as behavioral changes of clinical and translational research mentors. Given success across 16 diverse sites, this training may serve as a national model. Clin Trans Sci 2013; Volume 6: 26–33 PMID:23399086

Timing of translation in cross-language qualitative research.

PubMed

Santos, Hudson P O; Black, Amanda M; Sandelowski, Margarete

2015-01-01

Although there is increased understanding of language barriers in cross-language studies, the point at which language transformation processes are applied in research is inconsistently reported, or treated as a minor issue. Differences in translation timeframes raise methodological issues related to the material to be translated, as well as for the process of data analysis and interpretation. In this article we address methodological issues related to the timing of translation from Portuguese to English in two international cross-language collaborative research studies involving researchers from Brazil, Canada, and the United States. One study entailed late-phase translation of a research report, whereas the other study involved early phase translation of interview data. The timing of translation in interaction with the object of translation should be considered, in addition to the language, cultural, subject matter, and methodological competencies of research team members. © The Author(s) 2014.

Two-Photon and Second Harmonic Microscopy in Clinical and Translational Cancer Research

PubMed Central

PERRY, SETH W.; BURKE, RYAN M.; BROWN, EDWARD B.

2012-01-01

Application of two-photon microscopy (TPM) to translational and clinical cancer research has burgeoned over the last several years, as several avenues of pre-clinical research have come to fruition. In this review, we focus on two forms of TPM—two-photon excitation fluorescence microscopy, and second harmonic generation microscopy—as they have been used for investigating cancer pathology in ex vivo and in vivo human tissue. We begin with discussion of two-photon theory and instrumentation particularly as applicable to cancer research, followed by an overview of some of the relevant cancer research literature in areas that include two-photon imaging of human tissue biopsies, human skin in vivo, and the rapidly developing technology of two-photon microendoscopy. We believe these and other evolving two-photon methodologies will continue to help translate cancer research from the bench to the bedside, and ultimately bring minimally invasive methods for cancer diagnosis and treatment to therapeutic reality. PMID:22258888

Graduate Education for the Future: New Models and Methods for the Clinical and Translational Workforce

PubMed Central

Bennett, L. Michelle; Cicutto, Lisa; Gadlin, Howard; Moss, Marc; Tentler, John; Schoenbaum, Ellie

2015-01-01

Abstract This paper is the third in a five‐part series on the clinical and translational science educational pipeline, and it focuses on strategies for enhancing graduate research education to improve skills for interdisciplinary team science. Although some of the most cutting edge science takes place at the borders between disciplines, it is widely perceived that advancements in clinical and translational science are hindered by the “siloed” efforts of researchers who are comfortable working in their separate domains, and reluctant to stray from their own discipline when conducting research. Without appropriate preparation for career success as members and leaders of interdisciplinary teams, talented scientists may choose to remain siloed or to leave careers in clinical and translational science all together, weakening the pipeline and depleting the future biomedical research workforce. To address this threat, it is critical to begin at what is perhaps the most formative moment for academics: graduate training. This paper focuses on designs for graduate education, and contrasts the methods and outcomes from traditional educational approaches with those skills perceived as essential for the workforce of the future, including the capacity for research collaboration that crosses disciplinary boundaries. PMID:26643714

Translational errors as an early event in prion conversion.

PubMed

Hatin, I; Bidou, L; Cullin, C; Rousset, J P

2001-01-01

A prion is an infectious, altered form of a cellular protein which can self-propagate and affect normal phenotype. Prion conversion has been observed for mammalian and yeast proteins but molecular mechanisms that trigger this process remain unclear. Up to now, only post-translational models have been explored. In this work, we tested the hypothesis that co-translational events may be implicated in the conformation changes of the Ure2p protein of Saccharomyces cerevisiae. This protein can adopt a prion conformation leading to an [URE3] phenotype which can be easily assessed and quantified. We analyzed the effect of two antibiotics, known to affect translation, on [URE3] conversion frequency. For cells treated with G418 we observed a parallel increase of translational errors rate and frequency of [URE3] conversion. By contrast, cycloheximide which was not found to affect translational fidelity, has no influence on the induction of [URE3] phenotype. These results raise the possibility that the mechanism of prion conversion might not only involve alternative structures of strictly identical molecules but also aberrant proteins resulting from translational errors.

From bench to bedside and to health policies: ethics in translational research.

PubMed

Petrini, C

2011-01-01

Translation of biomedical research knowledge to effective clinical treatment is essential to the public good. The first level of translation ("from bench to bedside") corresponds to efficacy studies under controlled conditions with careful attention to internal validity (clinical research). The second level is the translation of results from clinical studies into everyday clinical practice and health decision making. The article summarises the ethical issues involved in the translation of biomedical research advances to clinical applications and to clinical practice. In particular, the article synthesizes theory from clinical ethics, operational design, and philosophy to examine the unique bioethical issues raised by the recent focus on translational research. In this framework safety of study participants and balancing of risk due to treatment with the potential benefits of the research are crucial: in clinical research there is a danger that the emphasis on advancements in scientific knowledge might prevail over the protection of the people who participate in research. These issues involve basic scientists, clinicians and bioethicists because of their application to comparative effectiveness research, clinical trials and evidence-based medicine, as well basic biomedical research.

Methods to Succeed in Effective Knowledge Translation in Clinical Practice.

PubMed

Kitson, Alison L; Harvey, Gillian

2016-05-01

To explore the evidence around facilitation as an intervention for the successful implementation of new knowledge into clinical practice. The revised version of the Promoting Action on Research Implementation in Health Services (PARIHS) framework, called the integrated or i-PARIHS framework, is used as the explanatory framework. This framework posits that evidence is a multidimensional construct embedded within innovation and operationalized by clinicians (individuals and within teams), working across multiple layers of context. Facilitation is the active ingredient that promotes successful implementation. An emerging body of evidence supports facilitation as a mechanism to getting new knowledge into clinical practice. Facilitation roles are divided into beginner, experienced, and expert facilitators. Facilitators can be internal or external to the organization they work in, and their skills and attributes complement other knowledge translation (KT) roles. Complex KT projects require facilitators who are experienced in implementation methods. Facilitation is positioned as the active ingredient to effectively introduce new knowledge into a clinical setting. Levels of facilitation experience are assessed in relation to the complexity of the KT task. Three core facilitation roles are identified, and structured interventions are established taking into account the nature and novelty of the evidence, the receptiveness of the clinicians, and the context or setting where the new evidence is to be introduced. Roles such as novice, experienced, and expert facilitators have important and complementary parts to play in enabling the successful translation of evidence into everyday practice in order to provide effective care for patients. © 2016 Sigma Theta Tau International.

Early skin-to-skin contact after cesarean section: A randomized clinical pilot study

PubMed Central

Kollmann, Martina; Aldrian, Lisa; Scheuchenegger, Anna; Mautner, Eva; Herzog, Sereina A.; Urlesberger, Berndt; Raggam, Reinhard B.; Lang, Uwe; Obermayer-Pietsch, Barbara; Klaritsch, Philipp

2017-01-01

Objective Early bonding by skin-to-skin contact (SSC) has been demonstrated to be beneficial for mothers and newborns following vaginal delivery. The aim of this study was to investigate the impact of intraoperative bonding (early SSC) after cesarean section on neonatal adaptation, maternal pain and stress response. Study design This prospective, randomized-controlled pilot study was performed at a single academic tertiary hospital (Department of Obstetrics and Gynecology, Medical University of Graz, Austria) between September 2013 and January 2014. Women were randomly assigned to intraoperative (“early”) SCC (n = 17) versus postoperative (“late”) SCC (n = 18). Main variables investigated were neonatal transition (Apgar score, arterial oxygen saturation, heart rate and temperature), maternal pain perception and both maternal and neonatal stress response by measuring the stress biomarkers salivary free cortisol and salivary alpha amylase. Results There was no evidence for differences in parameters reflecting neonatal transition or stress response between the ‘Early SSC Group’ and the ‘Late SSC Group’. Maternal salivary cortisol and alpha-amylase levels as well as maternal wellbeing and pain did not differ between the groups. However, the rise of maternal salivary alpha-amylase directly after delivery was higher in the ‘Early SSC Group’ compared to the ‘Late SSC Group’ (p = 0.004). Conclusions This study did not reveal significant risks for the newborn in terms of neonatal transition when early SSC is applied in the operating room. Maternal condition and stress marker levels did not differ either, although the rise of maternal salivary alpha-amylase directly after delivery was higher in the ‘Early SSC Group’ compared to the ‘Late SSC Group’, which may indicate a stressor sign due to intensive activation of the sympathetic-adreno-medullary-system. This needs to be further evaluated in a larger prospective randomized trial. Trial

[Early clinical diagnosis of acanthamoeba keratitis. A study of 70 eyes].

PubMed

Bernauer, W; Duguid, G I; Dart, J K

1996-05-01

Acanthamoeba keratitis is an uncommon condition which is usually associated with contact lens wear. The use of home made saline and poor hygiene are important risk factors. Early diagnosis is crucial since these cases respond well to medical therapy. The purpose of this paper is to describe and demonstrate early clinical signs. Between September 1992 and October 1994, 70 cases of acanthamoeba keratitis, one of them bilateral, were prospectively monitored at Moorfields Eye Hospital in London. A database of all patients was set up and the clinical findings, diagnostic methods, therapeutic interventions and the outcome were recorded. 66 patients (96%) were contact lens wearers, 64 of them (97%) wore soft lenses. The mean interval between first symptoms and correct diagnosis was 42%. The most frequent initial diagnoses were "unclear keratoconjunctivitis" and "herpetic keratitis". Early corneal findings included punctate keratopathy (n = 14; 20%), pseudodendrites (n = 4; 6%), epithelial infiltrates (n = 17; 24%), diffuse or focal sub-epithelial infiltrates (n = 36; 51%) and radial keratoneuritis (n = 5; 7%). Ring infiltrates (n = 13; 18%) and corneal ulceration (n = 13) were late signs. When the above corneal findings are observed, particularly in contact lens wearers, the diagnosis of acanthamoeba keratitis should be considered. The diagnosis of "herpetic keratitis" in association with contact lens wear should be encountered with scepticism.

Translating research findings of chronic kidney disease management to clinical practice: Challenges and opportunities.

PubMed

Stevens, Lesley Ann; Levin, Adeera

2004-01-01

Chronic Kidney disease (CKD) has been identified as a public health epidemic, fueled in part by improved outcomes of both diabetic and cardiac patient populations, as well as by the increasing recognition that it is possible to identify CKD at earlier stages. The estimated 8 to 10 million Americans that have CKD, with its concomitant morbidity and mortality, have the potential to overwhelm the current system of specialty practice medicine and health care resources. How can clinicians, clinician scientists, and health care administrators translate research findings into clinical practice in an effective manner to improve the care of this burgeoning patient group? The challenge of translating research into clinical care requires identification of that which we do and do not know, communication of knowledge between those who do and do not know, and efficient collection of information for systematic evaluation. This article will describe the challenges of translating current research findings into clinical practice. There is a need to identify the complexity of CKD disease processes and issues associated with delivery of care and to describe the difficulties in the dissemination of new knowledge to physicians. Because of the propensity of CKD to affect identifiable groups of patients, we will discuss the potential challenges of these strategies given the racial, ethnic, and cultural diversity in North America. A potential solution to these challenges is a new paradigm of "process-based medicine" that integrates clinical and basic science research findings with multidisciplinary and shared care models of health care delivery. In this context, attention to advances in information technology, the cognitive processes that underlie physician learning, and the findings of outcome research may ensure true integration of clinical research and clinical practice.

Our Fat Future: Translating Adipose Stem Cell Therapy.

PubMed

Nordberg, Rachel C; Loboa, Elizabeth G

2015-09-01

Human adipose stem cells (hASCs) have the potential to treat patients with a variety of clinical conditions. Recent advancements in translational research, regulatory policy, and industry have positioned hASCs on the threshold of clinical translation. We discuss the progress and challenges of bringing adipose stem cell therapy into mainstream clinical use. This article details the advances made in recent years that have helped move human adipose stem cell therapy toward mainstream clinical use from a translational research, regulatory policy, and industrial standpoint. Four recurrent themes in translational technology as they pertain to human adipose stem cells are discussed: automated closed-system operations, biosensors and real-time monitoring, biomimetics, and rapid manufacturing. In light of recent FDA guidance documents, regulatory concerns about adipose stem cell therapy are discussed. Finally, an update is provided on the current state of clinical trials and the emerging industry that uses human adipose stem cells. This article is expected to stimulate future studies in translational adipose stem cell research. ©AlphaMed Press.

Translating a US Early Palliative Care Model for Turkey and Singapore.

PubMed

Akyar, Imatullah; Dionne-Odom, James N; Yang, Grace Meijuan; Bakitas, Marie A

2018-01-01

The field of palliative care is growing in acceptance and sophistication globally. No longer considered just for patients at end-of-life, palliative care is now being incorporated early in the disease trajectory. Despite professional guidelines supporting early palliative care, there are few models that have been created that can be translated into practice cross-culturally. In the United States, the Educate, Nurture, Advise, Before, Life Ends (ENABLE) early palliative care telehealth model has demonstrated effectiveness in improving quality of life, mood, symptom relief, and survival for patients with cancer and is now being tested in patients with heart failure. Family caregivers of patients who have received ENABLE concurrent with their care recipients have also demonstrated positive outcomes in quality of life and caregiver burden. Internationally, a number of investigators are culturally adapting ENABLE for patients and family caregivers. While some elements of ENABLE, such as symptom management and self-care, and the caregiving role are relevant cross-culturally, others have been built on Western principles of self-determination or represent concepts such as advance care planning which will require more cultural adaptation. In addition, ENABLE was initially an in-person approach that was converted to telehealth to accommodate a rural population-it will be important to understand cultural norms related to receiving care by phone or if an in-person approach will be more culturally acceptable. This paper describes efforts in Turkey and Singapore to culturally adapt the ENABLE early palliative care principles for their countries.

Translating Research into Clinical Scale Manufacturing of Mesenchymal Stromal Cells

PubMed Central

Bieback, Karen; Kinzebach, Sven; Karagianni, Marianna

2010-01-01

It sounds simple to obtain sufficient numbers of cells derived from fetal or adult human tissues, isolate and/or expand the stem cells, and then transplant an appropriate number of these cells into the patient at the correct location. However, translating basic research into routine therapies is a complex multistep process which necessitates product regulation. The challenge relates to managing the expected therapeutic benefits with the potential risks and to balance the fast move to clinical trials with time-consuming cautious risk assessment. This paper will focus on the definition of mesenchymal stromal cells (MSCs), and challenges and achievements in the manufacturing process enabling their use in clinical studies. It will allude to different cellular sources, special capacities of MSCs, but also to current regulations, with a special focus on accessory material of human or animal origin, like media supplements. As cellular integrity and purity, formulation and lot release testing of the final product, validation of all procedures, and quality assurance are of utmost necessity, these topics will be addressed. PMID:21318154

Knowledge translation studies in paediatric emergency medicine: A systematic review of the literature.

PubMed

Wilson, Catherine L; Johnson, David; Oakley, Ed

2016-02-01

Systematic review of knowledge translation studies focused on paediatric emergency care to describe and assess the interventions used in emergency department settings. Electronic databases were searched for knowledge translation studies conducted in the emergency department that included the care of children. Two researchers independently reviewed the studies. From 1305 publications identified, 15 studies of varied design were included. Four were cluster-controlled trials, two patient-level randomised controlled trials, two interrupted time series, one descriptive study and six before and after intervention studies. Knowledge translation interventions were predominantly aimed at the treating clinician, with some targeting the organisation. Studies assessed effectiveness of interventions over 6-12 months in before and after studies, and 3-28 months in cluster or patient level controlled trials. Changes in clinical practice were variable, with studies on single disease and single treatments in a single site showing greater improvement. Evidence for effective methods to translate knowledge into practice in paediatric emergency medicine is fairly limited. More optimal study designs with more explicit descriptions of interventions are needed to facilitate other groups to effectively apply these procedures in their own setting. © 2016 The Authors Journal of Paediatrics and Child Health © 2016 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Early Career Mentoring for Translational Researchers: Mentee Perspectives on Challenges and Issues

PubMed Central

Keller, Thomas E.; Collier, Peter J.; Blakeslee, Jennifer E.; Logan, Kay; McCracken, Karen; Morris, Cynthia

2014-01-01

Background and purposes The education and training of early career biomedical translational researchers often involves formal mentoring by more experienced colleagues. This study investigated the nature of these mentoring relationships from the perspective of mentees. The objective was to understand the challenges and issues encountered by mentees in forming and maintaining productive mentoring relationships. Method Three focus groups (n=14) were conducted with early career researchers who had mentored career development awards. Thematic analysis identified, categorized, and illustrated the challenges and issues reported by mentees. Results The range of mentee challenges was reflected in five major categories: 1) network—finding appropriate mentors to meet various needs; 2) access—structuring schedules and opportunities to receive mentoring; 3) expectations—negotiating the mechanics of the mentoring relationship and its purpose; 4) alignment—managing mentor-mentee mismatches regarding interests, priorities, and goals; and 5) skills and supports—developing the institutional supports to be successful. Conclusions Mentoring relationships created for academic training and career development contend with tasks common to many other relationships, namely recognizing compatibility, finding time, establishing patterns, agreeing to goals, and achieving aims. Identifying challenges faced by mentees can facilitate the development of appropriate trainings and supports to foster mentoring relationships in academic and career settings. PMID:25010230

Translational research in genomics of Alzheimer's disease: a review of current practice and future perspectives.

PubMed

Mihaescu, Raluca; Detmar, Symone B; Cornel, Martina C; van der Flier, Wiesje M; Heutink, Peter; Hol, Elly M; Rikkert, Marcel G M Olde; van Duijn, Cornelia M; Janssens, A Cecile J W

2010-01-01

Alzheimer's disease (AD) is the most prevalent form of dementia and the number of cases is expected to increase exponentially worldwide. Three highly penetrant genes (AbetaPP, PSEN1, and PSEN2) explain only a small number of AD cases with a Mendelian transmission pattern. Many genes have been analyzed for association with non-Mendelian AD, but the only consistently replicated finding is APOE. At present, possibilities for prevention, early detection, and treatment of the disease are limited. Predictive and diagnostic genetic testing is available only in Mendelian forms of AD. Currently, APOE genotyping is not considered clinically useful for screening, presymptomatic testing, or clinical diagnosis of non-Mendelian AD. However, clinical management of the disease is expected to benefit from the rapid pace of discoveries in the genomics of AD. Following a recently developed framework for the continuum of translation research that is needed to move genetic discoveries to health applications, this paper reviews recent genetic discoveries as well as translational research on genomic applications in the prevention, early detection, and treatment of AD. The four phases of translation research include: 1) translation of basic genomics research into a potential health care application; 2) evaluation of the application for the development of evidence-based guidelines; 3) evaluation of the implementation and use of the application in health care practice; and 4) evaluation of the achieved population health impact. Most research on genome-based applications in AD is still in the first phase of the translational research framework, which means that further research is still needed before their implementation can be considered.

English Translations Of The First Clinical Reports On Narcolepsy And Cataplexy By Westphal And Gélineau In The Late 19th Century, With Commentary

PubMed Central

Schenck, Carlos H.; Bassetti, Claudio L.; Arnulf, Isabelle; Mignot, Emmanuel

2007-01-01

Study Objectives: To publish the first English translations, with commentary, of the original reports describing narcolepsy and cataplexy by Westphal in German (1877) and by Gélineau in French (1880). Methods: A professional translation service translated the 2 reports from either German or French to English, with each translation then being slightly edited by one of the authors. All authors then provided commentary. Results: Both Westphal and Gélineau correctly identified and described the new clinical entities of cataplexy and narcolepsy, with recurrent, self-limited sleep attacks and/or cataplectic attacks affecting 2 otherwise healthy people. Narcolepsy was named by Gélineau (and cataplexy was named by Henneberg in 1916). The evidence in both cases is sufficiently convincing to conclude that they were likely each HLA-DQB1*0602 positive and hypocretin deficient. Conclusions: The original descriptions of narcolepsy and cataplexy are now available in English, allowing for extensive clinical and historical commentary. Citations: Schenck CH; Bassetti CL; Arnulf I et al. English translations of the first clinical reports on narcolepsy and cataplexy by Westphal and Gélineau in the late 19th century, with commentary. J Clin Sleep Med 2007;3(3):301–311 PMID:17561602

The science of rotator cuff tears: translating animal models to clinical recommendations using simulation analysis.

PubMed

Mannava, Sandeep; Plate, Johannes F; Tuohy, Christopher J; Seyler, Thorsten M; Whitlock, Patrick W; Curl, Walton W; Smith, Thomas L; Saul, Katherine R

2013-07-01

The purpose of this article is to review basic science studies using various animal models for rotator cuff research and to describe structural, biomechanical, and functional changes to muscle following rotator cuff tears. The use of computational simulations to translate the findings from animal models to human scale is further detailed. A comprehensive review was performed of the basic science literature describing the use of animal models and simulation analysis to examine muscle function following rotator cuff injury and repair in the ageing population. The findings from various studies of rotator cuff pathology emphasize the importance of preventing permanent muscular changes with detrimental results. In vivo muscle function, electromyography, and passive muscle-tendon unit properties were studied before and after supraspinatus tenotomy in a rodent rotator cuff injury model (acute vs chronic). Then, a series of simulation experiments were conducted using a validated computational human musculoskeletal shoulder model to assess both passive and active tension of rotator cuff repairs based on surgical positioning. Outcomes of rotator cuff repair may be improved by earlier surgical intervention, with lower surgical repair tensions and fewer electromyographic neuromuscular changes. An integrated approach of animal experiments, computer simulation analyses, and clinical studies may allow us to gain a fundamental understanding of the underlying pathology and interpret the results for clinical translation.

Challenges and opportunities in clinical translation of biomedical optical spectroscopy and imaging

NASA Astrophysics Data System (ADS)

Wilson, Brian C.; Jermyn, Michael; Leblond, Frederic

2018-03-01

Medical devices face many hurdles before they enter routine clinical practice to address unmet clinical needs. This is also the case for biomedical optical spectroscopy and imaging systems that are used here to illustrate the opportunities and challenges involved. Following initial concept, stages in clinical translation include instrument development, preclinical testing, clinical prototyping, clinical trials, prototype-to-product conversion, regulatory approval, commercialization, and finally clinical adoption and dissemination, all in the face of potentially competing technologies. Optical technologies face additional challenges from their being extremely diverse, often targeting entirely different diseases and having orders-of-magnitude differences in resolution and tissue penetration. However, these technologies can potentially address a wide variety of unmet clinical needs since they provide rich intrinsic biochemical and structural information, have high sensitivity and specificity for disease detection and localization, and are practical, safe (minimally invasive, nonionizing), and relatively affordable.

Clinical and Other Risk Indicators for Early Periodontitis in Adults

PubMed Central

Tanner, Anne C.R.; Kent, Ralph; Van Dyke, Thomas; Sonis, Steven T.; Murray, Lora A.

2005-01-01

Background Periodontal diseases affect over half the adults in the U.S., disproportionately affecting minority populations. Periodontitis can be treated in early stages, but it is not clear what features indicate, or could be risk factors for, early stages of periodontal attachment loss. This study aimed to evaluate associations between clinical and other risk indicators of early periodontitis. Methods A cross-sectional evaluation of 225 healthy and early periodontitis adults aged 20 to 40 years was performed. Clinical measurements, demographic information, and smoking histories were recorded. Analyses evaluated demographic and clinical associations with health and early periodontitis disease categories and periodontal attachment loss. Patterns of attachment loss at interproximal and buccal/lingual sites were evaluated. Results Subject age, plaque, and measures of gingivitis exhibited associations with attachment loss and probing depth. More periodontal attachment loss was detected in African-American and Hispanic subjects compared to Asian and Caucasian subjects. Smoking history was associated with attachment loss. At interproximal sites, lower molars most frequently had attachment loss, whereas at buccal/lingual sites, higher proportions of lower bicuspid teeth demonstrated attachment loss compared with other sites. Conclusions In this study of subjects with minimal attachment loss, gingival inflammation was associated with early periodontitis. Lower molar interproximal sites were frequently associated with interproximal attachment loss, whereas lower bicuspid teeth were at risk for gingival recession on buccal surfaces. PMID:15857098

Nanoparticles for Biomedical Imaging: Fundamentals of Clinical Translation

PubMed Central

Choi, Hak Soo; Frangioni, John V.

2010-01-01

Because of their large size compared to small molecules, and their multi-functionality, nanoparticles (NPs) hold promise as biomedical imaging, diagnostic, and theragnostic agents. However, the key to their success hinges on a detailed understanding of their behavior after administration into the body. NP biodistribution, target binding, and clearance are a complex function of their physicochemical properties in serum, which include hydrodynamic diameter, solubility, stability, shape and flexibility, surface charge, composition, and formulation. Moreover, many materials used to construct NPs have real or potential toxicity, or may interfere with other medical tests. In this review, we discuss the design considerations that mediate NP behavior in the body and the fundamental principles that govern clinical translation. By analyzing those nanomaterials that have already received regulatory approval, most of which are actually therapeutic agents, we attempt to predict which types of NPs hold potential as diagnostic agents for biomedical imaging. Finally, using quantum dots as an example, we provide a framework for deciding whether an NP-based agent is the best choice for a particular clinical application. PMID:21084027

Translating basic research into clinical practice or what else do we have to learn about olfactory ensheathing cells?

PubMed

Radtke, Christine; Wewetzer, Konstantin

2009-06-12

Olfactory ensheathing cells (OECs) are Schwann cell-like glial cells of the olfactory system that have been shown to promote axonal regeneration and remyelination in a variety of different lesion paradigms. It is still a matter of debate in how far OECs differ from Schwann cells regarding their regenerative potential and molecular setup. The fact that OECs have been already used for transplantation in humans may imply that the need of the hour is the fine-tuning of clinical application details rather than to cross the bridge between laboratory animal and man. Considering the therapeutic transplantation of OECs, however, the basic question to date is not 'how' to translate but rather 'what' to translate into clinical practice. The aim of the present article is to provide a summary of the current literature and to define the open issues relevant for translating basic research on OECs into clinical practice.

Translating a US Early Palliative Care Model for Turkey and Singapore

PubMed Central

Akyar, Imatullah; Dionne-Odom, James N.; Yang, Grace Meijuan; Bakitas, Marie A.

2018-01-01

The field of palliative care is growing in acceptance and sophistication globally. No longer considered just for patients at end-of-life, palliative care is now being incorporated early in the disease trajectory. Despite professional guidelines supporting early palliative care, there are few models that have been created that can be translated into practice cross-culturally. In the United States, the Educate, Nurture, Advise, Before, Life Ends (ENABLE) early palliative care telehealth model has demonstrated effectiveness in improving quality of life, mood, symptom relief, and survival for patients with cancer and is now being tested in patients with heart failure. Family caregivers of patients who have received ENABLE concurrent with their care recipients have also demonstrated positive outcomes in quality of life and caregiver burden. Internationally, a number of investigators are culturally adapting ENABLE for patients and family caregivers. While some elements of ENABLE, such as symptom management and self-care, and the caregiving role are relevant cross-culturally, others have been built on Western principles of self-determination or represent concepts such as advance care planning which will require more cultural adaptation. In addition, ENABLE was initially an in-person approach that was converted to telehealth to accommodate a rural population-it will be important to understand cultural norms related to receiving care by phone or if an in-person approach will be more culturally acceptable. This paper describes efforts in Turkey and Singapore to culturally adapt the ENABLE early palliative care principles for their countries. PMID:29379831

From a Viewpoint of Clinical Settings: Pharmacoepidemiology as Reverse Translational Research (rTR).

PubMed

Kawakami, Junichi

2017-01-01

Clinical pharmacology and pharmacoepidemiology research may converge in practise. Pharmacoepidemiology is the study of pharmacotherapy and risk management in patient groups. For many drugs, adverse reaction(s) that were not seen and/or clarified during research and development stages have been reported in the real world. Pharmacoepidemiology can detect and verify adverse drug reactions as reverse translational research. Recently, development and effective use of medical information databases (MID) have been conducted in Japan and elsewhere for the purpose of post-marketing safety of drugs. The Ministry of Health, Labour and Welfare, Japan has been promoting the development of 10-million scale database in 10 hospitals and hospital groups as "the infrastructure project of medical information database (MID-NET)". This project enables estimation of the frequency of adverse reactions, the distinction between drug-induced reactions and basal health-condition changes, and usefulness verification of administrative measures of drug safety. However, because the database information is different from detailed medical records, construction of methodologies for the detection and evaluation of adverse reactions is required. We have been performing database research using medical information system in some hospitals to establish and demonstrate useful methods for post-marketing safety. In this symposium, we aim to discuss the possibility of reverse translational research from clinical settings and provide an introduction to our research.

Applying Process Improvement Methods to Clinical and Translational Research: Conceptual Framework and Case Examples

PubMed Central

Selker, Harry P.; Leslie, Laurel K.

2015-01-01

Abstract There is growing appreciation that process improvement holds promise for improving quality and efficiency across the translational research continuum but frameworks for such programs are not often described. The purpose of this paper is to present a framework and case examples of a Research Process Improvement Program implemented at Tufts CTSI. To promote research process improvement, we developed online training seminars, workshops, and in‐person consultation models to describe core process improvement principles and methods, demonstrate the use of improvement tools, and illustrate the application of these methods in case examples. We implemented these methods, as well as relational coordination theory, with junior researchers, pilot funding awardees, our CTRC, and CTSI resource and service providers. The program focuses on capacity building to address common process problems and quality gaps that threaten the efficient, timely and successful completion of clinical and translational studies. PMID:26332869

Cultural sensitivity or professional acculturation in early clinical experience?

PubMed

Whitford, David L; Hubail, Amal Redha

2014-11-01

This study aimed to explore the early clinical experience of medical students following the adaptation of an Early Patient Contact curriculum from a European culture in Ireland to an Arab culture in Bahrain. Medical students in Bahrain took part in an Early Patient Contact module modelled on a similar module from a partner medical school in Ireland. We used a qualitative approach employing thematic analysis of 54 student reflective logbooks. Particular attention was placed on reflections of cultural influences of experience in the course. Medical students undergoing this module received reported documented benefits of early clinical experience. However, students in Bahrain were exposed to cultural norms of the local Arab society including gender values, visiting the homes of strangers, language barriers and generous hospitality that led to additional challenges and learning for the medical students in acculturating to norms of the medical profession. Modules intended for curriculum adaptation between two cultures would be best served by a group of "core" learning outcomes with "secondary" outcomes culturally appropriate to each site. Within the context of the Arab culture, early clinical experience has the added benefit of allowing students to learn about both local and professional cultural norms, thereby facilitating integration of these two cultures.

[Historical Study of the Etymological Form and Translational Process of Gout (Tongfeng,)].

PubMed

Cho, Jae-Heung; Jung, Jae Young

2015-08-01

This study aims to address questions regarding the translation of 'gout' into 'tongfeng ()' in East Asia. To this end, the formation process of the origins, 'gout' from Western medicine and 'tongfeng' from Oriental medicine, and the translational process were investigated through the relevant records and literature dating from the 16th century on. Symptoms associated with gout were originally mentioned in ancient Egypt and various terminologies were used to refer to gout, such as podagra, cheiragra and gonogra. The word 'gout', which is derived from Latin, was used for the first time in the 13th century. The reason for this linguistic alteration is thought to be the need for a comprehensive term to cover the various terms for gout in symptomatic body parts, since it can occur concurrently in many joints. However, it took hundreds of years before gout was independently established as a medical term. In oriental medicine, terms describing diseases with features similar to gout include bibing (), lijiefeng (), baihufeng () and tongfeng (). Among them, the concept of 'tongfeng' has been established since the Jin and Yuan dynasties. The cause, prevention and various treatments for tongfeng were proposed throughout the Ming and Qing dynasties. The early translation of gout and tongfeng in East Asia, respectively, is estimated to have occurred in the 18th century. The first literature translating gout in China was 'An English and Chinese Vocabulary in the Court Dialect (yinghua yunfu lijie, )'. From the publication of this book until the late 19th century, gout was translated into an unfamiliar Chinese character 'Jiu feng jiao ()', likely because the translation was done mostly by foreign missionaries at the time, and they created a new word on the basis of Western medicine instead of researching and translating similar diseases in oriental medicine. In Japan, the first book translating gout was 'A Pocket Dictionary of the English and Japanese Language (Eiwa taiyaku

Computational Medicine: Translating Models to Clinical Care

PubMed Central

Winslow, Raimond L.; Trayanova, Natalia; Geman, Donald; Miller, Michael I.

2013-01-01

Because of the inherent complexity of coupled nonlinear biological systems, the development of computational models is necessary for achieving a quantitative understanding of their structure and function in health and disease. Statistical learning is applied to high-dimensional biomolecular data to create models that describe relationships between molecules and networks. Multiscale modeling links networks to cells, organs, and organ systems. Computational approaches are used to characterize anatomic shape and its variations in health and disease. In each case, the purposes of modeling are to capture all that we know about disease and to develop improved therapies tailored to the needs of individuals. We discuss advances in computational medicine, with specific examples in the fields of cancer, diabetes, cardiology, and neurology. Advances in translating these computational methods to the clinic are described, as well as challenges in applying models for improving patient health. PMID:23115356

Tissue engineering strategies in spinal arthrodesis: the clinical imperative and challenges to clinical translation.

PubMed

Evans, Nick R; Davies, Evan M; Dare, Chris J; Oreffo, Richard Oc

2013-01-01

Skeletal disorders requiring the regeneration or de novo production of bone present considerable reconstructive challenges and are one of the main driving forces for the development of skeletal tissue engineering strategies. The skeletal or mesenchymal stem cell is a fundamental requirement for osteogenesis and plays a pivotal role in the design and application of these strategies. Research activity has focused on incorporating the biological role of the mesenchymal stem cell with the developing fields of material science and gene therapy in order to create a construct that is not only capable of inducing host osteoblasts to produce bone, but is also osteogenic in its own right. This review explores the clinical need for reparative approaches in spinal arthrodesis, identifying recent tissue engineering strategies employed to promote spinal fusion, and considers the ongoing challenges to successful clinical translation.

Optimizing oncology therapeutics through quantitative translational and clinical pharmacology: challenges and opportunities.

PubMed

Venkatakrishnan, K; Friberg, L E; Ouellet, D; Mettetal, J T; Stein, A; Trocóniz, I F; Bruno, R; Mehrotra, N; Gobburu, J; Mould, D R

2015-01-01

Despite advances in biomedical research that have deepened our understanding of cancer hallmarks, resulting in the discovery and development of targeted therapies, the success rates of oncology drug development remain low. Opportunities remain for objective dose selection informed by exposure-response understanding to optimize the benefit-risk balance of novel therapies for cancer patients. This review article discusses the principles and applications of modeling and simulation approaches across the lifecycle of development of oncology therapeutics. Illustrative examples are used to convey the value gained from integration of quantitative clinical pharmacology strategies from the preclinical-translational phase through confirmatory clinical evaluation of efficacy and safety. © 2014 American Society for Clinical Pharmacology and Therapeutics.

Managing the potential and pitfalls during clinical translation of emerging stem cell therapies

PubMed Central

2014-01-01

We are moving into a new era of stem cell research where many possibilities for treatment of degenerative, chronic and/or fatal diseases and injuries are becoming primed for clinical trial. These reports have led millions of people worldwide to hope that regenerative medicine is about to revolutionise biomedicine: either through transplantation of cells grown in the laboratory, or by finding ways to stimulate a patient’s intrinsic stem cells to repair diseased and damaged organs. While major contributions of stem cells to drug discovery, safety and efficacy testing, as well as modelling ‘diseases in a dish’ are also expected, it is the in vivo use of stem cells that has captured the general public’s attention. However, public misconceptions of stem cell potential and applications can leave patients vulnerable to the influences of profit driven entities selling unproven treatments without solid scientific basis or appropriate clinical testing or follow up. This review provides a brief history of stem cell clinical translation together with an overview of the properties, potential, and current clinical application of various stem cell types. In doing so it presents a clearer picture of the inherent risks and opportunities associated with stem cell research translation, and thus offers a framework to help realise invested expectations more quickly, safely and effectively. PMID:24949190

Glutamine Randomized Studies in Early Life: The Unsolved Riddle of Experimental and Clinical Studies

PubMed Central

Briassouli, Efrossini; Briassoulis, George

2012-01-01

Glutamine may have benefits during immaturity or critical illness in early life but its effects on outcome end hardpoints are controversial. Our aim was to review randomized studies on glutamine supplementation in pups, infants, and children examining whether glutamine affects outcome. Experimental work has proposed various mechanisms of glutamine action but none of the randomized studies in early life showed any effect on mortality and only a few showed some effect on inflammatory response, organ function, and a trend for infection control. Although apparently safe in animal models (pups), premature infants, and critically ill children, glutamine supplementation does not reduce mortality or late onset sepsis, and its routine use cannot be recommended in these sensitive populations. Large prospectively stratified trials are needed to better define the crucial interrelations of “glutamine-heat shock proteins-stress response” in critical illness and to identify the specific subgroups of premature neonates and critically ill infants or children who may have a greater need for glutamine and who may eventually benefit from its supplementation. The methodological problems noted in the reviewed randomized experimental and clinical trials should be seriously considered in any future well-designed large blinded randomized controlled trial involving glutamine supplementation in critical illness. PMID:23019424

Effectiveness of a Clinic-Based Early Literacy Program in Changing Parent-Child Early Literacy Habits.

PubMed

Fricke, Jonathan; Navsaria, Dipesh; Mahony, Karin

2016-12-01

Reach Out and Read (ROR) improves children's development and kindergarten readiness by encouraging parents to routinely share books with their children. Primary care providers give age-appropriate books and anticipatory guidance on reading at each well-child visit. This study evaluated parent attitudes and behaviors of early literacy related to ROR participation in Wisconsin clinics. A survey of early literacy attitudes and behaviors was administered to parents of children ages 6 months to 5 years in 36 Wisconsin clinics. Ten clinics were established ROR sites (intervention group) and 26 clinics had applied to become ROR programs but had not yet initiated the program (control group). Parents at clinics with ROR programs were more likely to read with a child under the age of 6 months (OR=1.58, 95% CI, 1.05-2.38). Other literacy metrics trended toward improvement but none reached statistical significance. Paradoxically, the odds of parents reporting reading as a bedtime habit were decreased among those who participated in ROR. Our study finds mixed support of the effectiveness of ROR outside of academic settings. The apparent discrepancy between these results and those from national studies on ROR may be related to differences in respondent demographics and educational attainment or differences in program implementation and fidelity. We believe that the results will become clearer with future study as clinics are prospectively evaluated over time rather than being compared to non-ROR clinics in a cross-sectional snapshot.

Guinea pig models for translation of the developmental origins of health and disease hypothesis into the clinic.

PubMed

Morrison, Janna L; Botting, Kimberley J; Darby, Jack R T; David, Anna L; Dyson, Rebecca M; Gatford, Kathryn L; Gray, Clint; Herrera, Emilio A; Hirst, Jonathan J; Kim, Bona; Kind, Karen L; Krause, Bernardo J; Matthews, Stephen G; Palliser, Hannah K; Regnault, Timothy R H; Richardson, Bryan S; Sasaki, Aya; Thompson, Loren P; Berry, Mary J

2018-04-06

Over 30 years ago Professor David Barker first proposed the theory that events in early life could explain an individual's risk of non-communicable disease in later life: the developmental origins of health and disease (DOHaD) hypothesis. During the 1990s the validity of the DOHaD hypothesis was extensively tested in a number of human populations and the mechanisms underpinning it characterised in a range of experimental animal models. Over the past decade, researchers have sought to use this mechanistic understanding of DOHaD to develop therapeutic interventions during pregnancy and early life to improve adult health. A variety of animal models have been used to develop and evaluate interventions, each with strengths and limitations. It is becoming apparent that effective translational research requires that the animal paradigm selected mirrors the tempo of human fetal growth and development as closely as possible so that the effect of a perinatal insult and/or therapeutic intervention can be fully assessed. The guinea pig is one such animal model that over the past two decades has demonstrated itself to be a very useful platform for these important reproductive studies. This review highlights similarities in the in utero development between humans and guinea pigs, the strengths and limitations of the guinea pig as an experimental model of DOHaD and the guinea pig's potential to enhance clinical therapeutic innovation to improve human health. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Translational study of microRNAs and its application in kidney disease and hypertension research

PubMed Central

KRIEGEL, Alison J.; MLADINOV, Domagoj; LIANG, Mingyu

2015-01-01

MicroRNA research in humans and mammalian model organisms is in a crucial stage of development. Diagnostic and therapeutic values of microRNAs appear promising, but remain to be established. The physiological and pathophysiological significance of microRNAs is generally recognized, but much better understood in some organ systems and disease areas than others. In the present paper, we review several translational studies of microRNAs, including those showing the potential value of therapeutic agents targeting microRNAs and diagnostic or prognostic microRNA markers detectable in body fluids. We discuss the lessons learned and the experience gained from these studies. Several recent studies have begun to explore translational microRNA research in kidney disease and hypertension. Translational research of microRNAs in the kidney faces unique challenges, but provides many opportunities to develop and apply new methods, and to merge complementary basic and clinical approaches. PMID:22283365

Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

PubMed

Mugavero, Michael J; May, Margaret; Harris, Ross; Saag, Michael S; Costagliola, Dominique; Egger, Matthias; Phillips, Andrew; Günthard, Huldrych F; Dabis, Francois; Hogg, Robert; de Wolf, Frank; Fatkenheuer, Gerd; Gill, M John; Justice, Amy; D'Arminio Monforte, Antonella; Lampe, Fiona; Miró, Jose M; Staszewski, Schlomo; Sterne, Jonathan A C

2008-11-30

To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART. Observational cohort study of patients initiating ART between January 2000 and December 2005. The Antiretroviral Therapy Cohort Collaboration (ART-CC) is a collaboration of 15 HIV cohort studies from Canada, Europe, and the United States. A total of 13 546 antiretroviral-naïve HIV-positive patients initiating ART with efavirenz, nevirapine, lopinavir/ritonavir, nelfinavir, or abacavir as third drugs in combination with a zidovudine and lamivudine nucleoside reverse transcriptase inhibitor backbone. Short-term (24-week) virologic failure (>500 copies/ml) and clinical events within 2 years of ART initiation (incident AIDS-defining event, death, and a composite measure of these two outcomes). Compared with efavirenz as initial third drug, short-term virologic failure was more common with all other third drugs evaluated; nevirapine (adjusted odds ratio = 1.87, 95% confidence interval (CI) = 1.58-2.22), lopinavir/ritonavir (1.32, 95% CI = 1.12-1.57), nelfinavir (3.20, 95% CI = 2.74-3.74), and abacavir (2.13, 95% CI = 1.82-2.50). However, the rate of clinical events within 2 years of ART initiation appeared higher only with nevirapine (adjusted hazard ratio for composite outcome measure 1.27, 95% CI = 1.04-1.56) and abacavir (1.22, 95% CI = 1.00-1.48). Among antiretroviral-naïve patients initiating therapy, between-ART regimen, differences in short-term virologic failure do not necessarily translate to differences in clinical outcomes. Our results should be interpreted with caution because of the possibility of residual confounding by indication.

Metadata-driven Clinical Data Loading into i2b2 for Clinical and Translational Science Institutes.

PubMed

Post, Andrew R; Pai, Akshatha K; Willard, Richard; May, Bradley J; West, Andrew C; Agravat, Sanjay; Granite, Stephen J; Winslow, Raimond L; Stephens, David S

2016-01-01

Clinical and Translational Science Award (CTSA) recipients have a need to create research data marts from their clinical data warehouses, through research data networks and the use of i2b2 and SHRINE technologies. These data marts may have different data requirements and representations, thus necessitating separate extract, transform and load (ETL) processes for populating each mart. Maintaining duplicative procedural logic for each ETL process is onerous. We have created an entirely metadata-driven ETL process that can be customized for different data marts through separate configurations, each stored in an extension of i2b2 's ontology database schema. We extended our previously reported and open source Eureka! Clinical Analytics software with this capability. The same software has created i2b2 data marts for several projects, the largest being the nascent Accrual for Clinical Trials (ACT) network, for which it has loaded over 147 million facts about 1.2 million patients.

Metadata-driven Clinical Data Loading into i2b2 for Clinical and Translational Science Institutes

PubMed Central

Post, Andrew R.; Pai, Akshatha K.; Willard, Richard; May, Bradley J.; West, Andrew C.; Agravat, Sanjay; Granite, Stephen J.; Winslow, Raimond L.; Stephens, David S.

2016-01-01

Clinical and Translational Science Award (CTSA) recipients have a need to create research data marts from their clinical data warehouses, through research data networks and the use of i2b2 and SHRINE technologies. These data marts may have different data requirements and representations, thus necessitating separate extract, transform and load (ETL) processes for populating each mart. Maintaining duplicative procedural logic for each ETL process is onerous. We have created an entirely metadata-driven ETL process that can be customized for different data marts through separate configurations, each stored in an extension of i2b2 ‘s ontology database schema. We extended our previously reported and open source Eureka! Clinical Analytics software with this capability. The same software has created i2b2 data marts for several projects, the largest being the nascent Accrual for Clinical Trials (ACT) network, for which it has loaded over 147 million facts about 1.2 million patients. PMID:27570667

Multi-Dimensional Impact of the Public-Private Center for Translational Molecular Medicine (CTMM) in the Netherlands: Understanding New 21(st) Century Institutional Designs to Support Innovation-in-Society.

PubMed

Steuten, Lotte M

2016-05-01

Knowledge translation is at the epicenter of 21st century life sciences and integrative biology. Several innovative institutional designs have been formulated to cultivate knowledge translation. One of these organizational innovations has been the Center for Translational Molecular Medicine (CTMM), a multi-million public-private partnership in the Netherlands. The CTMM aims to accelerate molecular diagnostics and imaging technologies to forecast disease susceptibilities in healthy populations and early diagnosis and personalized treatment of patients. This research evaluated CTMM's impact on scientific, translational, clinical, and economic dimensions. A pragmatic, operationally-defined process indicators approach was used. Data were gathered from CTMM administrations, through a CTMM-wide survey (n = 167) and group interviews. We found that the CTMM focused on disease areas with high human, clinical, and economic burden to society (i.e., oncology, cardiovascular, neurologic, infection, and immunity diseases). CTMM displayed a robust scientific impact that rests 15%-80% above international reference values regarding publication volume and impact. Technology translation to the clinic was accelerated, with >50% of projects progressing from pre-clinical development to clinical testing within 5 years. Furthermore, CTMM has generated nearly 1500 Full Time Equivalent (FTE) of translational R&D capacity. Its positive impact on translational, (future) clinical, and economic aspects is recognized across all surveyed stakeholders. As organizational innovation is increasingly considered critical to forge linkages between life sciences discoveries and innovation-in-society, lessons learned from this study may inform other institutions with similar objectives such as the Clinical and Translational Science Awards (CTSA) Program of the National Institutes of Health (NIH) in the United States.

Clinical translation of polymyxin-based combination therapy: Facts, challenges and future opportunities.

PubMed

Zhang, Xueli; Guo, Fengmei; Shao, Hua; Zheng, Xiao

2017-02-01

The emergence and spread of multidrug resistant Gram-negative bacteria has led to a resurgence in the clinical use of polymyxin antibiotics. However, the prevalence of polymyxin resistance is on the rise at an alarming rate, motivating the idea of combination therapy to sustain the revival of these "old" antibiotics. Although ample evidence in favor of combination therapy has emerged, it seems impracticable and confusing to find a promising combination from the diverse reports or gain adequate information on the efficacy and safety profile. With a stagnating discovery pipeline of novel antimicrobials, there is a clear need to fill the knowledge gaps in translating these basic research data to beneficial clinical practice. In this review, we examined the factors and ambiguities that stand as major hurdles in bringing polymyxin combination therapy to bedside care, highlighting the importance and urgency of incorporating translational research insights into areas of difficulty. We also discussed future research priorities that are essential to gather the necessary evidence and insights for promoting the best possible use of polymyxins in combination therapy. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Functional Genomic and Proteomic Analysis Reveals Disruption of Myelin-Related Genes and Translation in a Mouse Model of Early Life Neglect

PubMed Central

Bordner, Kelly A.; George, Elizabeth D.; Carlyle, Becky C.; Duque, Alvaro; Kitchen, Robert R.; Lam, TuKiet T.; Colangelo, Christopher M.; Stone, Kathryn L.; Abbott, Thomas B.; Mane, Shrikant M.; Nairn, Angus C.; Simen, Arthur A.

2011-01-01

Early life neglect is an important public health problem which can lead to lasting psychological dysfunction. Good animal models are necessary to understand the mechanisms responsible for the behavioral and anatomical pathology that results. We recently described a novel model of early life neglect, maternal separation with early weaning (MSEW), that produces behavioral changes in the mouse that persist into adulthood. To begin to understand the mechanism by which MSEW leads to these changes we applied cDNA microarray, next-generation RNA-sequencing (RNA-seq), label-free proteomics, multiple reaction monitoring (MRM) proteomics, and methylation analysis to tissue samples obtained from medial prefrontal cortex to determine the molecular changes induced by MSEW that persist into adulthood. The results show that MSEW leads to dysregulation of markers of mature oligodendrocytes and genes involved in protein translation and other categories, an apparent downward biasing of translation, and methylation changes in the promoter regions of selected dysregulated genes. These findings are likely to prove useful in understanding the mechanism by which early life neglect affects brain structure, cognition, and behavior. PMID:21629843

Translating genomic information into clinical medicine: lung cancer as a paradigm.

PubMed

Levy, Mia A; Lovly, Christine M; Pao, William

2012-11-01

We are currently in an era of rapidly expanding knowledge about the genetic landscape and architectural blueprints of various cancers. These discoveries have led to a new taxonomy of malignant diseases based upon clinically relevant molecular alterations in addition to histology or tissue of origin. The new molecularly based classification holds the promise of rational rather than empiric approaches for the treatment of cancer patients. However, the accelerated pace of discovery and the expanding number of targeted anti-cancer therapies present a significant challenge for healthcare practitioners to remain informed and up-to-date on how to apply cutting-edge discoveries into daily clinical practice. In this Perspective, we use lung cancer as a paradigm to discuss challenges related to translating genomic information into the clinic, and we present one approach we took at Vanderbilt-Ingram Cancer Center to address these challenges.

Ultra-deep sequencing of ribosome-associated poly-adenylated RNA in early Drosophila embryos reveals hundreds of conserved translated sORFs.

PubMed

Li, Hongmei; Hu, Chuansheng; Bai, Ling; Li, Hua; Li, Mingfa; Zhao, Xiaodong; Czajkowsky, Daniel M; Shao, Zhifeng

2016-12-01

There is growing recognition that small open reading frames (sORFs) encoding peptides shorter than 100 amino acids are an important class of functional elements in the eukaryotic genome, with several already identified to play critical roles in growth, development, and disease. However, our understanding of their biological importance has been hindered owing to the significant technical challenges limiting their annotation. Here we combined ultra-deep sequencing of ribosome-associated poly-adenylated RNAs with rigorous conservation analysis to identify a comprehensive population of translated sORFs during early Drosophila embryogenesis. In total, we identify 399 sORFs, including those previously annotated but without evidence of translational capacity, those found within transcripts previously classified as non-coding, and those not previously known to be transcribed. Further, we find, for the first time, evidence for translation of many sORFs with different isoforms, suggesting their regulation is as complex as longer ORFs. Furthermore, many sORFs are found not associated with ribosomes in late-stage Drosophila S2 cells, suggesting that many of the translated sORFs may have stage-specific functions during embryogenesis. These results thus provide the first comprehensive annotation of the sORFs present during early Drosophila embryogenesis, a necessary basis for a detailed delineation of their function in embryogenesis and other biological processes. © The Author 2016. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

Applying knowledge-anchored hypothesis discovery methods to advance clinical and translational research: the OAMiner project

PubMed Central

Jackson, Rebecca D; Best, Thomas M; Borlawsky, Tara B; Lai, Albert M; James, Stephen; Gurcan, Metin N

2012-01-01

The conduct of clinical and translational research regularly involves the use of a variety of heterogeneous and large-scale data resources. Scalable methods for the integrative analysis of such resources, particularly when attempting to leverage computable domain knowledge in order to generate actionable hypotheses in a high-throughput manner, remain an open area of research. In this report, we describe both a generalizable design pattern for such integrative knowledge-anchored hypothesis discovery operations and our experience in applying that design pattern in the experimental context of a set of driving research questions related to the publicly available Osteoarthritis Initiative data repository. We believe that this ‘test bed’ project and the lessons learned during its execution are both generalizable and representative of common clinical and translational research paradigms. PMID:22647689

Merging clinical chemistry biomarker data with a COPD database - building a clinical infrastructure for proteomic studies.

PubMed

Eriksson, Jonatan; Andersson, Simone; Appelqvist, Roger; Wieslander, Elisabet; Truedsson, Mikael; Bugge, May; Malm, Johan; Dahlbäck, Magnus; Andersson, Bo; Fehniger, Thomas E; Marko-Varga, György

2016-01-01

Data from biological samples and medical evaluations plays an essential part in clinical decision making. This data is equally important in clinical studies and it is critical to have an infrastructure that ensures that its quality is preserved throughout its entire lifetime. We are running a 5-year longitudinal clinical study, KOL-Örestad, with the objective to identify new COPD (Chronic Obstructive Pulmonary Disease) biomarkers in blood. In the study, clinical data and blood samples are collected from both private and public health-care institutions and stored at our research center in databases and biobanks, respectively. The blood is analyzed by Mass Spectrometry and the results from this analysis then linked to the clinical data. We built an infrastructure that allows us to efficiently collect and analyze the data. We chose to use REDCap as the EDC (Electronic Data Capture) tool for the study due to its short setup-time, ease of use, and flexibility. REDCap allows users to easily design data collection modules based on existing templates. In addition, it provides two functions that allow users to import batches of data; through a web API (Application Programming Interface) as well as by uploading CSV-files (Comma Separated Values). We created a software, DART (Data Rapid Translation), that translates our biomarker data into a format that fits REDCap's CSV-templates. In addition, DART is configurable to work with many other data formats as well. We use DART to import our clinical chemistry data to the REDCap database. We have shown that a powerful and internationally adopted EDC tool such as REDCap can be extended so that it can be used efficiently in proteomic studies. In our study, we accomplish this by using DART to translate our clinical chemistry data to a format that fits the templates of REDCap.

Computational framework to support integration of biomolecular and clinical data within a translational approach.

PubMed

Miyoshi, Newton Shydeo Brandão; Pinheiro, Daniel Guariz; Silva, Wilson Araújo; Felipe, Joaquim Cezar

2013-06-06

The use of the knowledge produced by sciences to promote human health is the main goal of translational medicine. To make it feasible we need computational methods to handle the large amount of information that arises from bench to bedside and to deal with its heterogeneity. A computational challenge that must be faced is to promote the integration of clinical, socio-demographic and biological data. In this effort, ontologies play an essential role as a powerful artifact for knowledge representation. Chado is a modular ontology-oriented database model that gained popularity due to its robustness and flexibility as a generic platform to store biological data; however it lacks supporting representation of clinical and socio-demographic information. We have implemented an extension of Chado - the Clinical Module - to allow the representation of this kind of information. Our approach consists of a framework for data integration through the use of a common reference ontology. The design of this framework has four levels: data level, to store the data; semantic level, to integrate and standardize the data by the use of ontologies; application level, to manage clinical databases, ontologies and data integration process; and web interface level, to allow interaction between the user and the system. The clinical module was built based on the Entity-Attribute-Value (EAV) model. We also proposed a methodology to migrate data from legacy clinical databases to the integrative framework. A Chado instance was initialized using a relational database management system. The Clinical Module was implemented and the framework was loaded using data from a factual clinical research database. Clinical and demographic data as well as biomaterial data were obtained from patients with tumors of head and neck. We implemented the IPTrans tool that is a complete environment for data migration, which comprises: the construction of a model to describe the legacy clinical data, based on an

Analytical challenges translating mass spectrometry-based phosphoproteomics from discovery to clinical applications

PubMed Central

Iliuk, Anton B.; Arrington, Justine V.; Tao, Weiguo Andy

2014-01-01

Phosphoproteomics is the systematic study of one of the most common protein modifications in high throughput with the aim of providing detailed information of the control, response, and communication of biological systems in health and disease. Advances in analytical technologies and strategies, in particular the contributions of high-resolution mass spectrometers, efficient enrichments of phosphopeptides, and fast data acquisition and annotation, have catalyzed dramatic expansion of signaling landscapes in multiple systems during the past decade. While phosphoproteomics is an essential inquiry to map high-resolution signaling networks and to find relevant events among the apparently ubiquitous and widespread modifications of proteome, it presents tremendous challenges in separation sciences to translate it from discovery to clinical practice. In this mini-review, we summarize the analytical tools currently utilized for phosphoproteomic analysis (with focus on MS), progresses made on deciphering clinically relevant kinase-substrate networks, MS uses for biomarker discovery and validation, and the potential of phosphoproteomics for disease diagnostics and personalized medicine. PMID:24890697

'Don't blame the middle man': an exploratory qualitative study to explore the experiences of translators breaking bad news.

PubMed

Prentice, Joanna; Nelson, Annmarie; Baillie, Jessica; Osborn, Hannah; Noble, Simon

2014-07-01

Healthcare professionals find breaking bad news difficult and upsetting. Increasing cultural diversity has led to a greater number of patients whose first language differs to that of the healthcare provider, with more patients requiring a translator to facilitate communication. Hospitals often ask non-clinical translators to facilitate breaking bad news. We sought to explore the experiences of translators within a specialist oncology centre. Following ethical and governance approvals, semi-structured interviews were undertaken with five translators recruited from the specialist oncology centre. Interviews were audiotaped and transcribed verbatim. The data were analysed thematically, with major themes and subthemes identified. Outpatient setting of a regional cancer centre. Translators serving a regional cancer centre. Qualitative data identified through thematic analysis. Major themes included the significant emotional impact of translating distressing information, the challenges of accurately conveying information in a culturally congruent format and the need for formal briefing, debriefing and support. Subthemes included feeling guilty for divulging distressing news, being the focus of patients' distress or anger, and feeling in conflict with the patient or family and issues surrounding confidentiality. Translators also felt a strong sense of advocacy for the patients and found encounters with death and dying emotionally challenging. The increasing use of translators in the care of patients with advanced cancer is increasingly resulting in lay people being subject to similar emotional pressures faced by clinical staff, yet without the necessary formal training or support mechanisms that are recommended for clinicians. This exploratory study highlights the training and support needs of non-clinical staff as identifying a unique set of communication challenges faced by translators. © The Royal Society of Medicine.

Longitudinal study of clinical prognostic factors in patients with early rheumatoid arthritis: the PREDICT study.

PubMed

Bird, Paul; Nicholls, Dave; Barrett, Rina; de Jager, Julien; Griffiths, Hedley; Roberts, Lynden; Tymms, Kathleen; McCloud, Philip; Littlejohn, Geoffrey

2017-04-01

To assess the association between baseline clinical prognostic factors and subsequent Disease Activity Score of 28 joints (DAS28) remission in early rheumatoid arthritis (RA). Data were collected using point of care clinical software from participating rheumatology centres. Patients aged 18 years or over whose date of clinical onset of RA was within the previous 12-24 months, who had at least 6 months of follow-up data and a DAS28-ESR (erythrocyte sedimentation rate) score recorded between 12 and 24 months from first being seen for RA were included. Data collected included baseline demographics, mode of disease onset, pattern of joint involvement at onset, smoking status, DAS28, rheumatoid factor (RF), anti-citrullinated peptide antibodies (ACPA), time from symptom onset to presentation and disease activity at baseline. Univariate and multivariate logistic regression of DAS28-ESR remission between 12 and 24 months after first assessment were performed. Data from 1017 patients were analyzed: 70% female; mean age 60 years (SD: 14.7); 70% RF-positive, 58% ACPA-positive. The strongest age and sex adjusted baseline predictors of DAS28-ESR remission at 12-24 months were remission at baseline (odds ratio [OR]: 4.49, 95% CI: 2.17-9.29, P < 0.001), being male (OR: 2.42, 95% CI: 1.46-4.01, P < 0.001), abstaining from alcohol (P < 0.001) and being lower weight (OR: 0.98, 95% CI: 0.97-1.00, P = 0.015). There was no statistically significant association between joint onset patterns, mode of onset, RF, ACPA or smoking status. In this observational study, patients with early RA at risk of not achieving remission include those with high disease activity at baseline, women, those who drink alcohol and those with higher body weight. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Translational Epidemiology in Psychiatry

PubMed Central

Weissman, Myrna M.; Brown, Alan S.; Talati, Ardesheer

2012-01-01

Translational research generally refers to the application of knowledge generated by advances in basic sciences research translated into new approaches for diagnosis, prevention, and treatment of disease. This direction is called bench-to-bedside. Psychiatry has similarly emphasized the basic sciences as the starting point of translational research. This article introduces the term translational epidemiology for psychiatry research as a bidirectional concept in which the knowledge generated from the bedside or the population can also be translated to the benches of laboratory science. Epidemiologic studies are primarily observational but can generate representative samples, novel designs, and hypotheses that can be translated into more tractable experimental approaches in the clinical and basic sciences. This bedside-to-bench concept has not been explicated in psychiatry, although there are an increasing number of examples in the research literature. This article describes selected epidemiologic designs, providing examples and opportunities for translational research from community surveys and prospective, birth cohort, and family-based designs. Rapid developments in informatics, emphases on large sample collection for genetic and biomarker studies, and interest in personalized medicine—which requires information on relative and absolute risk factors—make this topic timely. The approach described has implications for providing fresh metaphors to communicate complex issues in interdisciplinary collaborations and for training in epidemiology and other sciences in psychiatry. PMID:21646577

Tendon Tissue Engineering: Progress, Challenges, and Translation to the Clinic

PubMed Central

Shearn, Jason T.; Kinneberg, Kirsten R.C.; Dyment, Nathaniel A.; Galloway, Marc T.; Kenter, Keith; Wylie, Christopher; Butler, David L.

2013-01-01

The tissue engineering field has made great strides in understanding how different aspects of tissue engineered constructs (TECs) and the culture process affect final tendon repair. However, there remain significant challenges in developing strategies that will lead to a clinically effective and commercially successful product. In an effort to increase repair quality, a better understanding of normal development, and how it differs from adult tendon healing, may provide strategies to improve tissue engineering. As tendon tissue engineering continues to improve, the field needs to employ more clinically relevant models of tendon injury such as degenerative tendons. We need to translate successes to larger animal models to begin exploring the clinical implications of our treatments. By advancing the models used to validate our TECs, we can help convince our toughest customer, the surgeon, that our products will be clinically efficacious. As we address these challenges in musculoskeletal tissue engineering, the field still needs to address the commercialization of products developed in the laboratory. TEC commercialization faces numerous challenges because each injury and patient is unique. This review aims to provide tissue engineers with a summary of important issues related to engineering tendon repairs and potential strategies for producing clinically successful products. PMID:21625053

Closing the clinical gap: translating best practice knowledge to performance with guidelines implementation.

PubMed

Ishii, Lisa E

2013-06-01

Unsustainable health care costs coupled with opportunity for improvement in health care outcomes in the United States are stimulating meaningful transformation in the way we deliver care. One approach in this transformation focuses on minimizing unnecessary variation in physician practices, instead focusing on evidence-based medicine in a more uniform manner. Clinical practice guidelines contain evidence-based recommendations, articulate goals of care, and can help to reduce unnecessary variation. While thousands of clinical practice guidelines are in existence, a clinical gap exists between knowledge and clinical performance. With thoughtful guidelines implementation strategies in place, organizations can begin to close the gap and translate best practice knowledge into care. Health systems that have done this effectively have seen improved clinical outcomes, improved patient satisfaction, and lower cost per patient.

Translating research into clinical practice: integrating robotics into neurorehabilitation for stroke survivors.

PubMed

Backus, Deborah; Winchester, Patricia; Tefertiller, Candace

2010-01-01

Technological advances continue to infuse the field of neurorehabilitation with both excitement and apprehension. A challenge for clinicians is to determine which of the growing number of devices or interventions available should be incorporated into their clinical practice, and when and with whom they should be offered, in order to best assist their patients in attaining the highest level of function and quality of life. Robotics is one area of technology that has seen robust growth in rehabilitation applications, so much so that the presence of robotic devices in rehabilitation centers has become an expectation among patients, their caregivers, and therapists. Although rehabilitation robotic devices afford the opportunity to provide high doses of repetitive movement in a reliable and controllable manner, the role they play in the continuum of clinical care remains uncertain. The focus of this article is on translating the empirical evidence related to the application of rehabilitation robotics for improving lower limb and walking function in a manner that the clinician, or any stakeholder, will be able to incorporate relevant findings into clinical practice. A process is outlined and applied to a recent review of the literature related to the use of robotics for the treatment of lower limb and walking function in persons with stroke. This process provides the reader with a tool that can be applied to the translation and implementation of evidence related to any intervention for any client with neurological injury or disease.

Inspiring hope-A physician's responsibility, translating the science into clinical practice.

PubMed

Temple, Walley J

2018-03-01

Giving hope to patients is our responsibility. It is the essence of a meaningful practice in medicine. Science now allows us to understand this complex and multidimensional human dynamic, and translate it into clinical practice. Quantitative research has shown hope is strong even in terminal illness. Through qualitative methodology hope fostering strategies and hope hindering behaviors have been identified. This exciting new knowledge facilitates the challenging task of disclosure of bad news while enabling hope. © 2017 Wiley Periodicals, Inc.

Embedding clinical interventions into observational studies

PubMed Central

Newman, Anne B.; Avilés-Santa, M. Larissa; Anderson, Garnet; Heiss, Gerardo; Howard, Wm. James; Krucoff, Mitchell; Kuller, Lewis H.; Lewis, Cora E.; Robinson, Jennifer G.; Taylor, Herman; Treviño, Roberto P.; Weintraub, William

2017-01-01

Novel approaches to observational studies and clinical trials could improve the cost-effectiveness and speed of translation of research. Hybrid designs that combine elements of clinical trials with observational registries or cohort studies should be considered as part of a long-term strategy to transform clinical trials and epidemiology, adapting to the opportunities of big data and the challenges of constrained budgets. Important considerations include study aims, timing, breadth and depth of the existing infrastructure that can be leveraged, participant burden, likely participation rate and available sample size in the cohort, required sample size for the trial, and investigator expertise. Community engagement and stakeholder (including study participants) support are essential for these efforts to succeed. PMID:26611435

Batten Disease: Clinical Aspects, Molecular Mechanisms, Translational Science, and Future Directions

PubMed Central

Dolisca, Sarah-Bianca; Mehta, Mitali; Pearce, David A.; Mink, Jonathan W.; Maria, Bernard L.

2014-01-01

The neuronal ceroid lipofuscinoses, collectively the most common neurodegenerative disorders of childhood, are primarily caused by an autosomal recessive genetic mutation leading to a lysosomal storage disease. Clinically these diseases manifest at varying ages of onset, and associated symptoms include cognitive decline, movement disorders, seizures, and retinopathy. The underlying cell biology and biochemistry that cause the clinical phenotypes of neuronal ceroid lipofuscinoses are still being elaborated. The 2012 Neurobiology of Disease in Children Symposium, held in conjunction with the 41st Annual Meeting of the Child Neurology Society, aimed to (1) provide a survey of the currently accepted forms of neuronal ceroid lipofuscinoses and their associated genetic mutations and clinical phenotypes; (2) highlight the specific pathology of Batten disease; (3) discuss the contemporary understanding of the molecular mechanisms that lead to pathology; and (4) introduce strategies that are being translated from bench to bedside as potential therapeutics. PMID:23838031

Successfully accelerating translational research at an academic medical center: the University of Michigan-Coulter translational research partnership program.

PubMed

Pienta, Kenneth J

2010-12-01

Translational research encompasses the effective movement of new knowledge and discoveries into new approaches for prevention, diagnosis, and treatment of disease. There are many roadblocks to successful bench to bedside research, but few have received as much recent attention as the "valley of death". The valley of death refers to the lack of funding and support for research that moves basic science discoveries into diagnostics, devices, and treatments in humans, and is ascribed to be the result of companies unwilling to fund research development that may not result in a drug or device that will be utilized in the clinic and conversely, the fact that researchers have no access to the funding needed to carry out preclinical and early clinical development to demonstrate potential efficacy in humans. The valley of death also exists because bridging the translational gap is dependent on successfully managing an additional four risks: scientific, intellectual property, market, and regulatory. The University of Michigan (UM) has partnered with the Wallace H. Coulter Foundation (CF) to create a model providing an infrastructure to overcome these risks. This model is easily adoptable to other academic medical centers (AMCs). © 2010 Wiley Periodicals, Inc.

Relevance of Rodent Models of Depression in Clinical Practice: Can We Overcome the Obstacles in Translational Neuropsychiatry?

PubMed

Söderlund, Johan; Lindskog, Maria

2018-04-23

The diagnosis of a mental disorder generally depends on clinical observations and phenomenological symptoms reported by the patient. The definition of a given diagnosis is criteria based and relies on the ability to accurately interpret subjective symptoms and complex behavior. This type of diagnosis comprises a challenge to translate to reliable animal models, and these translational uncertainties hamper the development of new treatments. In this review, we will discuss how depressive-like behavior can be induced in rodents, and the relationship between these models and depression in humans. Specifically, we suggest similarities between triggers of depressive-like behavior in animal models and human conditions known to increase the risk of depression, for example exhaustion and bullying. Although we acknowledge the potential problems in comparing animal findings to human conditions, such comparisons are useful for understanding the complexity of depression, and we highlight the need to develop clinical diagnoses and animal models in parallel to overcome translational uncertainties.

Proteomic analysis of tissue samples in translational breast cancer research.

PubMed

Gromov, Pavel; Moreira, José M A; Gromova, Irina

2014-06-01

In the last decade, many proteomic technologies have been applied, with varying success, to the study of tissue samples of breast carcinoma for protein expression profiling in order to discover protein biomarkers/signatures suitable for: characterization and subtyping of tumors; early diagnosis, and both prognosis and prediction of outcome of chemotherapy. The purpose of this review is to critically appraise what has been achieved to date using proteomic technologies and to bring forward novel strategies - based on the analysis of clinically relevant samples - that promise to accelerate the translation of basic discoveries into the daily breast cancer clinical practice. In particular, we address major issues in experimental design by reviewing the strengths and weaknesses of current proteomic strategies in the context of the analysis of human breast tissue specimens.

Setting Global Standards for Stem Cell Research and Clinical Translation: The 2016 ISSCR Guidelines.

PubMed

Daley, George Q; Hyun, Insoo; Apperley, Jane F; Barker, Roger A; Benvenisty, Nissim; Bredenoord, Annelien L; Breuer, Christopher K; Caulfield, Timothy; Cedars, Marcelle I; Frey-Vasconcells, Joyce; Heslop, Helen E; Jin, Ying; Lee, Richard T; McCabe, Christopher; Munsie, Megan; Murry, Charles E; Piantadosi, Steven; Rao, Mahendra; Rooke, Heather M; Sipp, Douglas; Studer, Lorenz; Sugarman, Jeremy; Takahashi, Masayo; Zimmerman, Mark; Kimmelman, Jonathan

2016-06-14

The International Society for Stem Cell Research (ISSCR) presents its 2016 Guidelines for Stem Cell Research and Clinical Translation (ISSCR, 2016). The 2016 guidelines reflect the revision and extension of two past sets of guidelines (ISSCR, 2006; ISSCR, 2008) to address new and emerging areas of stem cell discovery and application and evolving ethical, social, and policy challenges. These guidelines provide an integrated set of principles and best practices to drive progress in basic, translational, and clinical research. The guidelines demand rigor, oversight, and transparency in all aspects of practice, providing confidence to practitioners and public alike that stem cell science can proceed efficiently and remain responsive to public and patient interests. Here, we highlight key elements and recommendations in the guidelines and summarize the recommendations and deliberations behind them. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Nuclear factors involved in mitochondrial translation cause a subgroup of combined respiratory chain deficiency.

PubMed

Kemp, John P; Smith, Paul M; Pyle, Angela; Neeve, Vivienne C M; Tuppen, Helen A L; Schara, Ulrike; Talim, Beril; Topaloglu, Haluk; Holinski-Feder, Elke; Abicht, Angela; Czermin, Birgit; Lochmüller, Hanns; McFarland, Robert; Chinnery, Patrick F; Chrzanowska-Lightowlers, Zofia M A; Lightowlers, Robert N; Taylor, Robert W; Horvath, Rita

2011-01-01

Mutations in several mitochondrial DNA and nuclear genes involved in mitochondrial protein synthesis have recently been reported in combined respiratory chain deficiency, indicating a generalized defect in mitochondrial translation. However, the number of patients with pathogenic mutations is small, implying that nuclear defects of mitochondrial translation are either underdiagnosed or intrauterine lethal. No comprehensive studies have been reported on large cohorts of patients with combined respiratory chain deficiency addressing the role of nuclear genes affecting mitochondrial protein synthesis to date. We investigated a cohort of 52 patients with combined respiratory chain deficiency without causative mitochondrial DNA mutations, rearrangements or depletion, to determine whether a defect in mitochondrial translation defines the pathomechanism of their clinical disease. We followed a combined approach of sequencing known nuclear genes involved in mitochondrial protein synthesis (EFG1, EFTu, EFTs, MRPS16, TRMU), as well as performing in vitro functional studies in 22 patient cell lines. The majority of our patients were children (<15 years), with an early onset of symptoms <1 year of age (65%). The most frequent clinical presentation was mitochondrial encephalomyopathy (63%); however, a number of patients showed cardiomyopathy (33%), isolated myopathy (15%) or hepatopathy (13%). Genomic sequencing revealed compound heterozygous mutations in the mitochondrial transfer ribonucleic acid modifying factor (TRMU) in a single patient only, presenting with early onset, reversible liver disease. No pathogenic mutation was detected in any of the remaining 51 patients in the other genes analysed. In vivo labelling of mitochondrial polypeptides in 22 patient cell lines showed overall (three patients) or selective (four patients) defects of mitochondrial translation. Immunoblotting for mitochondrial proteins revealed decreased steady state levels of proteins in some patients

A qualitative study evaluating causality attribution for serious adverse events during early phase oncology clinical trials.

PubMed

Mukherjee, Som D; Coombes, Megan E; Levine, Mitch; Cosby, Jarold; Kowaleski, Brenda; Arnold, Andrew

2011-10-01

In early phase oncology trials, novel targeted therapies are increasingly being tested in combination with traditional agents creating greater potential for enhanced and new toxicities. When a patient experiences a serious adverse event (SAE), investigators must determine whether the event is attributable to the investigational drug or not. This study seeks to understand the clinical reasoning, tools used and challenges faced by the researchers who assign causality to SAE's. Thirty-two semi-structured interviews were conducted with medical oncologists and trial coordinators at six Canadian academic cancer centres. Interviews were recorded and transcribed verbatim. Individual interview content analysis was followed by thematic analysis across the interview set. Our study found that causality assessment tends to be a rather complex process, often without complete clinical and investigational data at hand. Researchers described using a common processing strategy whereby they gather pertinent information, eliminate alternative explanations, and consider whether or not the study drug resulted in the SAE. Many of the interviewed participants voiced concern that causality assessments are often conducted quickly and tend to be highly subjective. Many participants were unable to identify any useful tools to help in assigning causality and welcomed more objectivity in the overall process. Attributing causality to SAE's is a complex process. Clinical trial researchers apply a logical system of reasoning, but feel that the current method of assigning causality could be improved. Based on these findings, future research involving the development of a new causality assessment tool specifically for use in early phase oncology clinical trials may be useful.

2015 Guidance on cancer immunotherapy development in early-phase clinical studies.

PubMed

2015-12-01

The development of cancer immunotherapies is progressing rapidly with a variety of technological approaches. They consist of "cancer vaccines", which are based on the idea of vaccination, "effector cell therapy", classified as passive immunotherapy, and "inhibition of immunosuppression", which intends to break immunological tolerance to autoantigens or immunosuppressive environments characterizing antitumor immune responses. Recent reports showing clinical evidence of efficacy of immune checkpoint inhibitors and adoptive immunotherapies with tumor-infiltrating lymphocytes and tumor-specific receptor gene-modified T cells indicate the beginning of a new era for cancer immunotherapy. This guidance summarizes ideas that will be helpful to those who plan to develop cancer immunotherapy. The aims of this guidance are to discuss and offer important points in early phase clinical studies of innovative cancer immunotherapy, with future progress in this field, and to contribute to the effective development of cancer immunotherapy aligned with the scope of regulatory science. This guidance covers cancer vaccines, effector cell therapy, and inhibition of immunosuppression, including immune checkpoint inhibitors. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Global informetric perspective studies on translational medical research

PubMed Central

2013-01-01

Background Translational medical research literature has increased rapidly in the last few decades and played a more and more important role during the development of medicine science. The main aim of this study is to evaluate the global performance of translational medical research during the past few decades. Methods Bibliometric, social network analysis, and visualization technologies were used for analyzing translational medical research performance from the aspects of subject categories, journals, countries, institutes, keywords, and MeSH terms. Meanwhile, the co-author, co-words and cluster analysis methods were also used to trace popular topics in translational medical research related work. Results Research output suggested a solid development in translational medical research, in terms of increasing scientific production and research collaboration. We identified the core journals, mainstream subject categories, leading countries, and institutions in translational medical research. There was an uneven distribution of publications at authorial, institutional, and national levels. The most commonly used keywords that appeared in the articles were “translational research”, “translational medicine”, “biomarkers”, “stroke”, “inflammation”, “cancer”, and “breast cancer”. Conclusions The subject categories of “Research & Experimental Medicine”, “Medical Laboratory Technology”, and “General & Internal Medicine” play a key role in translational medical research both in production and in its networks. Translational medical research and CTS, etc. are core journals of translational research. G7 countries are the leading nations for translational medical research. Some developing countries, such as P.R China, also play an important role in the communication of translational research. The USA and its institutions play a dominant role in the production, collaboration, citations and high quality articles. The research trends in

Designing Interventions Informed by Scientific Knowledge About Effects of Early Adversity: A Translational Neuroscience Agenda for Next Generation Addictions Research

PubMed Central

Fisher, Philip A.; Berkman, Elliot T.

2015-01-01

In spite of extensive scientific knowledge about the neurobiological systems and neural pathways underlying addictions, only limited progress has been made to reduce the population-level incidence of addictions by using prevention and treatment programs. In this area of research the translation of basic neuroscience of causal mechanisms to effective interventions has not been fully realized. In this article we describe how an understanding of the effects of early adverse experiences on brain and biological development may provide new opportunities to achieve impact at scale with respect to reduction of addictions. We propose four categories of new knowledge that translational neuroscience investigations of addictions should incorporate to be successful. We then describe a translational neuroscience-informed smoking cessation intervention based on this model. PMID:26985399

Clinical symptoms predict concurrent social and global functioning in an early psychosis sample.

PubMed

Cacciotti-Saija, Cristina; Langdon, Robyn; Ward, Philip B; Hickie, Ian B; Guastella, Adam J

2018-04-01

Although well established in chronic schizophrenia, the key determinants of functioning remain unknown during the early phase of a psychotic disorder. The aim of this study was to comprehensively examine the social cognitive, basic neurocognitive and clinical predictors of concurrent social functioning and global functioning in an early psychosis sample. This study examined the relationship between social cognition, basic neurocognition and clinical symptoms with concurrent functioning in 51 early psychosis individuals. Assessments included a range of self-report, observational and clinician-rated measures of cognitive, symptom severity and functioning domains. Results revealed a significant association between self-reported social function and lower levels of both social interaction anxiety and negative psychotic symptoms. A significant association was also observed between lower levels of negative psychotic symptoms and observed social functioning. Lastly, results demonstrated a significant association between reduced negative psychotic symptoms and clinician-rated global functioning. Clinical domains such as negative symptoms and social interaction anxiety significantly contribute to an optimal model predicting outcome during the early phase of a psychotic disorder. These clinical features may also provide useful markers of an individual's capacity for social participation. Clinical implications include the need for early targeted intervention to address social anxiety and negative psychotic symptoms to facilitate optimum patient outcome. © 2015 Wiley Publishing Asia Pty Ltd.

Development of Translational Methods in Spectral Analysis of Human Infant Crying and Rat Pup Ultrasonic Vocalizations for Early Neurobehavioral Assessment

PubMed Central

Zeskind, Philip Sanford; McMurray, Matthew S.; Garber, Kristin A.; Neuspiel, Juliana M.; Cox, Elizabeth T.; Grewen, Karen M.; Mayes, Linda C.; Johns, Josephine M.

2011-01-01

The purpose of this article is to describe the development of translational methods by which spectrum analysis of human infant crying and rat pup ultrasonic vocalizations (USVs) can be used to assess potentially adverse effects of various prenatal conditions on early neurobehavioral development. The study of human infant crying has resulted in a rich set of measures that has long been used to assess early neurobehavioral insult due to non-optimal prenatal environments, even among seemingly healthy newborn and young infants. In another domain of study, the analysis of rat put USVs has been conducted via paradigms that allow for better experimental control over correlated prenatal conditions that may confound findings and conclusions regarding the effects of specific prenatal experiences. The development of translational methods by which cry vocalizations of both species can be analyzed may provide the opportunity for findings from the two approaches of inquiry to inform one another through their respective strengths. To this end, we present an enhanced taxonomy of a novel set of common measures of cry vocalizations of both human infants and rat pups based on a conceptual framework that emphasizes infant crying as a graded and dynamic acoustic signal. This set includes latency to vocalization onset, duration and repetition rate of expiratory components, duration of inter-vocalization-intervals and spectral features of the sound, including the frequency and amplitude of the fundamental and dominant frequencies. We also present a new set of classifications of rat pup USV waveforms that include qualitative shifts in fundamental frequency, similar to the presence of qualitative shifts in fundamental frequency that have previously been related to insults to neurobehavioral integrity in human infants. Challenges to the development of translational analyses, including the use of different terminologies, methods of recording, and spectral analyses are discussed, as well as

Translational Educational Research

PubMed Central

Issenberg, S. Barry; Cohen, Elaine R.; Barsuk, Jeffrey H.; Wayne, Diane B.

2012-01-01

Medical education research contributes to translational science (TS) when its outcomes not only impact educational settings, but also downstream results, including better patient-care practices and improved patient outcomes. Simulation-based medical education (SBME) has demonstrated its role in achieving such distal results. Effective TS also encompasses implementation science, the science of health-care delivery. Educational, clinical, quality, and safety goals can only be achieved by thematic, sustained, and cumulative research programs, not isolated studies. Components of an SBME TS research program include motivated learners, curriculum grounded in evidence-based learning theory, educational resources, evaluation of downstream results, a productive research team, rigorous research methods, research resources, and health-care system acceptance and implementation. National research priorities are served from translational educational research. National funding priorities should endorse the contribution and value of translational education research. PMID:23138127

Translating Proper Nouns: A Case Study on English Translation of Hafez's Lyrics

ERIC Educational Resources Information Center

Shirinzadeh, Seyed Alireza; Mahadi, Tengku Sepora Tengku

2014-01-01

Proper nouns are regarded so simple that they might be taken for granted in translation explorations. Some may believe that they should not be translated in transmitting source texts to target texts. But, it is not the case; if one looks at present translations, he will notice that different strategies might be applied for translating proper…

Translational Research from an Informatics Perspective

NASA Technical Reports Server (NTRS)

Bernstam, Elmer; Meric-Bernstam, Funda; Johnson-Throop, Kathy A.; Turley, James P.; Smith, Jack W.

2007-01-01

Clinical and translational research (CTR) is an essential part of a sustainable global health system. Informatics is now recognized as an important en-abler of CTR and informaticians are increasingly called upon to help CTR efforts. The US National Institutes of Health mandated biomedical informatics activity as part of its new national CTR grant initiative, the Clinical and Translational Science Award (CTSA). Traditionally, translational re-search was defined as the translation of laboratory discoveries to patient care (bench to bedside). We argue, however, that there are many other kinds of translational research. Indeed, translational re-search requires the translation of knowledge dis-covered in one domain to another domain and is therefore an information-based activity. In this panel, we will expand upon this view of translational research and present three different examples of translation to illustrate the point: 1) bench to bedside, 2) Earth to space and 3) academia to community. We will conclude with a discussion of our local translational research efforts that draw on each of the three examples.

Insights and limits of translational research in critical care medicine.

PubMed

Pène, Frédéric; Ait-Oufella, Hafid; Taccone, Fabio Silvio; Monneret, Guillaume; Sharshar, Tarek; Tamion, Fabienne; Mira, Jean-Paul

2015-01-01

Experimental research has always been the cornerstone of pathophysiological and therapeutic advances in critical care medicine, where clinical observations and basic research mutually fed each other in a so-called translational approach. The objective of this review is to address the different aspects of translational research in the field of critical care medicine. We herein highlighted some demonstrative examples including the animal-to-human approach to study host-pathogen interactions, the human-to-animal approach for sepsis-induced immunosuppression, the still restrictive human approach to study critical illness-related neuromyopathy, and the technological developments to assess the microcirculatory changes in critically ill patients. These examples not only emphasize how translational research resulted in major improvements in the comprehension of the pathophysiology of severe clinical conditions and offered promising perspectives in critical care medicine but also point out the obstacles to translate such achievements into clinical practice.

Challenges in translating endpoints from trials to observational cohort studies in oncology

PubMed Central

Ording, Anne Gulbech; Cronin-Fenton, Deirdre; Ehrenstein, Vera; Lash, Timothy L; Acquavella, John; Rørth, Mikael; Sørensen, Henrik Toft

2016-01-01

Clinical trials are considered the gold standard for examining drug efficacy and for approval of new drugs. Medical databases and population surveillance registries are valuable resources for post-approval observational research, which are increasingly used in studies of benefits and risk of new cancer drugs. Here, we address the challenges in translating endpoints from oncology trials to observational studies. Registry-based cohort studies can investigate real-world safety issues – including previously unrecognized concerns – by examining rare endpoints or multiple endpoints at once. In contrast to clinical trials, observational cohort studies typically do not exclude real-world patients from clinical practice, such as old and frail patients with comorbidity. The observational cohort study complements the clinical trial by examining the effectiveness of interventions applied in clinical practice and by providing evidence on long-term clinical outcomes, which are often not feasible to study in a clinical trial. Various endpoints can be included in clinical trials, such as hard endpoints, soft endpoints, surrogate endpoints, and patient-reported endpoints. Each endpoint has it strengths and limitations for use in research studies. Endpoints used in oncology trials are often not applicable in observational cohort studies which are limited by the setting of standard clinical practice and by non-standardized endpoint determination. Observational studies can be more helpful moving research forward if they restrict focus to appropriate and valid endpoints. PMID:27354827

Access to Core Facilities and Other Research Resources Provided by the Clinical and Translational Science Awards

PubMed Central

2012-01-01

Abstract  Principal investigators who received Clinical and Translational Science Awards created academic homes for biomedical research. They developed program‐supported websites to offer coordinated access to a range of core facilities and other research resources. Visitors to the 60 websites will find at least 170 generic services, which this review has categorized in the following seven areas: (1) core facilities, (2) biomedical informatics, (3) funding, (4) regulatory knowledge and support, (5) biostatistics, epidemiology, research design, and ethics, (6) participant and clinical interaction resources, and (7) community engagement. In addition, many websites facilitate access to resources with search engines, navigators, studios, project development teams, collaboration tools, communication systems, and teaching tools. Each of these websites may be accessed from a single site, http://www.CTSAcentral.org. The ability to access the research resources from 60 of the nation's academic health centers presents a novel opportunity for investigators engaged in clinical and translational research. Clin Trans Sci 2012; Volume #: 1–5 PMID:22376262

Access to core facilities and other research resources provided by the Clinical and Translational Science Awards.

PubMed

Rosenblum, Daniel

2012-02-01

Principal investigators who received Clinical and Translational Science Awards created academic homes for biomedical research. They developed program-supported websites to offer coordinated access to a range of core facilities and other research resources. Visitors to the 60 websites will find at least 170 generic services, which this review has categorized in the following seven areas: (1) core facilities, (2) biomedical informatics, (3) funding, (4) regulatory knowledge and support, (5) biostatistics, epidemiology, research design, and ethics, (6) participant and clinical interaction resources, and (7) community engagement. In addition, many websites facilitate access to resources with search engines, navigators, studios, project development teams, collaboration tools, communication systems, and teaching tools. Each of these websites may be accessed from a single site, http://www.CTSAcentral.org. The ability to access the research resources from 60 of the nation's academic health centers presents a novel opportunity for investigators engaged in clinical and translational research. © 2012 Wiley Periodicals, Inc.

Neuroimaging in mental health care: voices in translation

PubMed Central

Borgelt, Emily L.; Buchman, Daniel Z.; Illes, Judy

2012-01-01

Images of brain function, popularly called “neuroimages,” have become a mainstay of contemporary communication about neuroscience and mental health. Paralleling media coverage of neuroimaging research and the high visibility of clinics selling scans is pressure from sponsors to move basic research about brain function along the translational pathway. Indeed, neuroimaging may offer benefits to mental health care: early or tailored intervention, opportunities for education and planning, and access to resources afforded by objectification of disorder. However, risks of premature technology transfer, such as misinterpretation, misrepresentation, and increased stigmatization, could compromise patient care. The insights of stakeholder groups about neuroimaging for mental health care are a largely untapped resource of information and guidance for translational efforts. We argue that the insights of key stakeholders—including researchers, healthcare providers, patients, and families—have an essential role to play upstream in professional, critical, and ethical discourse surrounding neuroimaging in mental health. Here we integrate previously orthogonal lines of inquiry involving stakeholder research to describe the translational landscape as well as challenges on its horizon. PMID:23097640

The Translatability of Metaphor: Study and Investigation

ERIC Educational Resources Information Center

Alghbban, Mohammed

2011-01-01

The appropriate handling of the metaphorical meaning during translation, along with maximizing its level of equivalence in the target language, is going to be my central focus through the course of this dissertation. Unlike many contributions that attempt to reconcile the problem of translating metaphor, this study has come to approach the subject…

OncDRS: An integrative clinical and genomic data platform for enabling translational research and precision medicine

PubMed Central

Orechia, John; Pathak, Ameet; Shi, Yunling; Nawani, Aniket; Belozerov, Andrey; Fontes, Caitlin; Lakhiani, Camille; Jawale, Chetan; Patel, Chetansharan; Quinn, Daniel; Botvinnik, Dmitry; Mei, Eddie; Cotter, Elizabeth; Byleckie, James; Ullman-Cullere, Mollie; Chhetri, Padam; Chalasani, Poornima; Karnam, Purushotham; Beaudoin, Ronald; Sahu, Sandeep; Belozerova, Yelena; Mathew, Jomol P.

2015-01-01

We live in the genomic era of medicine, where a patient's genomic/molecular data is becoming increasingly important for disease diagnosis, identification of targeted therapy, and risk assessment for adverse reactions. However, decoding the genomic test results and integrating it with clinical data for retrospective studies and cohort identification for prospective clinical trials is still a challenging task. In order to overcome these barriers, we developed an overarching enterprise informatics framework for translational research and personalized medicine called Synergistic Patient and Research Knowledge Systems (SPARKS) and a suite of tools called Oncology Data Retrieval Systems (OncDRS). OncDRS enables seamless data integration, secure and self-navigated query and extraction of clinical and genomic data from heterogeneous sources. Within a year of release, the system has facilitated more than 1500 research queries and has delivered data for more than 50 research studies. PMID:27054074

Translational mini-screw implant research.

PubMed

Rossouw, Emile

2014-09-01

It is important to thoroughly test new materials as well as techniques when these innovations are to be utilized in the human clinical situation. Translational research fills this important niche. The purpose of translational research is to establish the continuity of evidence from the laboratory to the clinic and in so-doing, provide evidence that the material is functioning appropriately and that the process in the human will be successful. This concept applies to the mini-screw implant; which, has been very successfully introduced into the orthodontic armamentarium over the last decade for application as a temporary anchorage device. The examples of translational research that will be illustrated in this paper have paved the way to ensure that clinicians have evidence to confidently utilize mini-screw implants in orthodontic practice. Needless to say, more studies are needed to ensure a safe, effective and efficient manner to practice orthodontics. © 2014 British Orthodontic Society.

Cell-Based Meniscus Repair and Regeneration: At the Brink of Clinical Translation?

PubMed Central

Korpershoek, Jasmijn V.; de Windt, Tommy S.; Hagmeijer, Michella H.; Vonk, Lucienne A.; Saris, Daniel B. F.

2017-01-01

Background: Meniscus damage can be caused by trauma or degeneration and is therefore common among patients of all ages. Repair or regeneration of the menisci could be of great importance not only for pain relief or regaining function but also to prevent degenerative disease and osteoarthritis. Current treatment does not offer consistent long-term improvement. Although preclinical research focusing on augmentation of meniscal tear repair and regeneration after meniscectomy is encouraging, clinical translation remains difficult. Purpose: To systematically evaluate the literature on in vivo meniscus regeneration and explore the optimal cell sources and conditions for clinical translation. We aimed at thorough evaluation of current evidence as well as clarifying the challenges for future preclinical and clinical studies. Study Design: Systematic review. Methods: A search was conducted using the electronic databases of MEDLINE, Embase, and the Cochrane Collaboration. Search terms included meniscus, regeneration, and cell-based. Results: After screening 81 articles based on title and abstract, 51 articles on in vivo meniscus regeneration could be included; 2 additional articles were identified from the references. Repair and regeneration of the meniscus has been described by intra-articular injection of multipotent mesenchymal stromal (stem) cells from adipose tissue, bone marrow, synovium, or meniscus or the use of these cell types in combination with implantable or injectable scaffolds. The use of fibrochondrocytes, chondrocytes, and transfected myoblasts for meniscus repair and regeneration is limited to the combination with different scaffolds. The comparative in vitro and in vivo studies mentioned in this review indicate that the use of allogeneic cells is as successful as the use of autologous cells. In addition, the implantation or injection of cell-seeded scaffolds increased tissue regeneration and led to better structural organization compared with scaffold

Embedding clinical interventions into observational studies.

PubMed

Newman, Anne B; Avilés-Santa, M Larissa; Anderson, Garnet; Heiss, Gerardo; Howard, Wm James; Krucoff, Mitchell; Kuller, Lewis H; Lewis, Cora E; Robinson, Jennifer G; Taylor, Herman; Treviño, Roberto P; Weintraub, William

2016-01-01

Novel approaches to observational studies and clinical trials could improve the cost-effectiveness and speed of translation of research. Hybrid designs that combine elements of clinical trials with observational registries or cohort studies should be considered as part of a long-term strategy to transform clinical trials and epidemiology, adapting to the opportunities of big data and the challenges of constrained budgets. Important considerations include study aims, timing, breadth and depth of the existing infrastructure that can be leveraged, participant burden, likely participation rate and available sample size in the cohort, required sample size for the trial, and investigator expertise. Community engagement and stakeholder (including study participants) support are essential for these efforts to succeed. Copyright © 2015. Published by Elsevier Inc.

PODCAST: From Lost in Translation to Paradise Found: Enabling Protein Biomarker Method Transfer by Mass Spectrometry | Office of Cancer Clinical Proteomics Research

Cancer.gov

Translation of novel biomarkers into clinical care for the evaluation of therapeutic safety and efficacy has been slow, partly attributable to the cost and complexity of immunoassay development.  The potential for liquid chromatography-tandem mass spectrometry (LC-MS/MS) to streamline the translation of novel protein biomarkers is profound.  Drs. Henry Rodriguez and Andrew Hoofnagle discuss what the future may be for clinical proteomics. This is an American Association for Clinical Chemistry (AACC) podcast.

Not lost in translation: Emerging clinical importance of the G protein-coupled estrogen receptor GPER.

PubMed

Barton, Matthias

2016-07-01

It has been 20years that the G protein-coupled estrogen receptor (GPER) was cloned as the orphan receptor GPR30 from multiple cellular sources, including vascular endothelial cells. Here, I will provide an overview of estrogen biology and the historical background leading to the discovery of rapid vascular estrogen signaling. I will also review the recent advances in the understanding of the mechanisms underlying GPER function, its role in physiology and disease, some of the currently available GPER-targeting drugs approved for clinical use such as SERMs (selective estrogen receptor modulators) and SERDs (selective estrogen receptor downregulators). Many of currently used drugs such as tamoxifen, raloxifene, or faslodex™/fulvestrant were discovered targeting GPER many years after they had been introduced to the clinics for entirely different purposes. This has important implications for the clinical use of these drugs and their modes of action, which I have termed 'reverse translational medicine'. In addition, environmental pollutants known as 'endocrine disruptors' have been found to bind to GPER. This article also discusses recent evidence in these areas as well as opportunities in translational clinical medicine and GPER research, including medical genetics, personalized medicine, prevention, and its theranostic use. Copyright © 2016 Elsevier Inc. All rights reserved.

Translational research: a concept analysis.

PubMed

Wendler, M Cecilia; Kirkbride, Geri; Wade, Kristen; Ferrell, Lynne

2013-01-01

BACKGROUND/CONCEPTUAL FRAMEWORK: Little is known about which approaches facilitate adoption and sustainment of evidence-based practice change in the highly complex care environments that constitute clinical practice today. The purpose of this article was to complete a concept analysis of translational research using a modified Walker and Avant approach. DESIGN/DATA COLLECTION: Using a rigorous and thorough review of the recent health care literature generated by a deep electronic search from 2004-2011, 85 appropriate documents were retrieved. Close reading of the articles by three coresearchers yielded an analysis of the emerging concept of translational research. Using the iterative process described by Walker and Avant, a tentative definition of the concept of translational research, along with antecedents and consequences were identified. Implications for health care professionals in education, practice, and research are offered. Further research is needed to determine the adequacy of the definition, to identify empirical referents, and to guide theory development. The study resulted in a theoretical definition of the concept of translational research, along with identification of antecedents and consequences and a description of an ideal or model case to illustrate the definition. Implications for practice and education include the importance of focusing on translational research approaches that may reduce the research-practice gap in health care, thereby improving patient care delivery. Research is needed to determine the usefulness of the definition in health care clinical practice.

Chest electrical impedance tomography examination, data analysis, terminology, clinical use and recommendations: consensus statement of the TRanslational EIT developmeNt stuDy group

PubMed Central

Frerichs, Inéz; Amato, Marcelo B P; van Kaam, Anton H; Tingay, David G; Zhao, Zhanqi; Grychtol, Bartłomiej; Bodenstein, Marc; Gagnon, Hervé; Böhm, Stephan H; Teschner, Eckhard; Stenqvist, Ola; Mauri, Tommaso; Torsani, Vinicius; Camporota, Luigi; Schibler, Andreas; Wolf, Gerhard K; Gommers, Diederik; Leonhardt, Steffen; Adler, Andy

2017-01-01

Electrical impedance tomography (EIT) has undergone 30 years of development. Functional chest examinations with this technology are considered clinically relevant, especially for monitoring regional lung ventilation in mechanically ventilated patients and for regional pulmonary function testing in patients with chronic lung diseases. As EIT becomes an established medical technology, it requires consensus examination, nomenclature, data analysis and interpretation schemes. Such consensus is needed to compare, understand and reproduce study findings from and among different research groups, to enable large clinical trials and, ultimately, routine clinical use. Recommendations of how EIT findings can be applied to generate diagnoses and impact clinical decision-making and therapy planning are required. This consensus paper was prepared by an international working group, collaborating on the clinical promotion of EIT called TRanslational EIT developmeNt stuDy group. It addresses the stated needs by providing (1) a new classification of core processes involved in chest EIT examinations and data analysis, (2) focus on clinical applications with structured reviews and outlooks (separately for adult and neonatal/paediatric patients), (3) a structured framework to categorise and understand the relationships among analysis approaches and their clinical roles, (4) consensus, unified terminology with clinical user-friendly definitions and explanations, (5) a review of all major work in thoracic EIT and (6) recommendations for future development (193 pages of online supplements systematically linked with the chief sections of the main document). We expect this information to be useful for clinicians and researchers working with EIT, as well as for industry producers of this technology. PMID:27596161

Challenges and perspective of drug repurposing strategies in early phase clinical trials.

PubMed

Kato, Shumei; Moulder, Stacy L; Ueno, Naoto T; Wheler, Jennifer J; Meric-Bernstam, Funda; Kurzrock, Razelle; Janku, Filip

2015-01-01

Despite significant investments in the development of new agents only 5% of cancer drugs entering Phase I clinical trials are ultimately approved for routine clinical cancer care. Drug repurposing strategies using novel combinations of previously tested anticancer agents could reduce the cost and improve treatment outcomes. At MD Anderson Cancer Center, early phase clinical trials with drug repurposing strategies demonstrated promising outcomes in patients with both rare and common treatment refractory advanced cancers. Despite clinical efficacy advancing drug repurposing strategies in the clinical trial trajectory beyond early phase studies has been challenging mainly due to lack of funding and interest from the pharmaceutical industry. In this review, we delineate our experience and challenges with drug repurposing strategies.

Conflicts of interest in translational research

PubMed Central

Parks, Malcolm R; Disis, Mary L

2004-01-01

Translational research requires a team approach to scientific inquiry and product development. Translational research teams consist of basic and clinical scientists who can be members of both academic and industrial communities. The conception, pre-clinical testing, and clinical evaluation of a diagnostic or therapeutic approach demands an intense interaction between investigators with diverse backgrounds. As the barriers between industry and academia are removed, issues of potential conflict of interest become more complex. Translational researchers must become aware of the situations which constitute conflict of interest and understand how such conflicts can impact their research programs. Finally, the translational research community must participate in the dialogue ongoing in the public and private sectors and help shape the rules that will govern conflicts that arise during the evolution of their research programs. PMID:15301694

Transition to Independence: Characteristics and Outcomes of Mentored Career Development (KL2) Scholars at Clinical and Translational Science Award Institutions.

PubMed

Sweeney, Carol; Schwartz, Lisa S; Toto, Robert; Merchant, Carol; Fair, Alecia S; Gabrilove, Janice L

2017-04-01

To describe the transition from mentored to independent research funding for clinical and translational scholars supported by institutional KL2 Mentored Career Development programs. In 2013, faculty leaders at Clinical and Translational Science Award institutions completed an online survey, reporting characteristics of scholars in their KL2 programs from 2006 to 2013. The primary outcome variable was a report that the scholar had received independent funding as a principal investigator. Data analysis included descriptive summaries and mixed-effects regression models. Respondents from 48 institutions (of 62 eligible; 77%) provided information about 914 KL2 scholars. Of those, 620 (68%) were medical doctors, 114 (12%) had other clinical training, and 177 (19%) were nonclinician PhDs. Fifty-three percent (487) were female; 12% (108/865) were members of racial or ethnic groups underrepresented in medicine (URM). After completing KL2 training, 96% (558/582) remained engaged in research. Among scholars who completed KL2 training two or more years earlier, 39% (149/374) received independent funding. Independent funding was from non-National Institutes of Health (NIH) sources (120 scholars) more often than from NIH (101 scholars). The odds of a nonclinician attaining independent funding were twice those of a clinician (odds ratio 2.05; 95% confidence interval 1.11-3.78). Female and URM scholars were as likely as male and non-URM scholars to attain independent funding. KL2 programs supported the transition to independent funding for clinical and translational scientists. Female and URM scholars were well represented. Future studies should consider non-NIH funding sources when assessing the transition to research independence.

Nursing students' early exposure to clinical practice: an innovation in curriculum development.

PubMed

Hoyles, A; Pollard, C; Lees, S; Glossop, D

2000-08-01

This paper describes a pilot study addressing issues surrounding the balance and status given to both theory and practice in the foundation part of a pre-registration programme. Contemporary thinking seems to suggest that there is a need to reverse recent trends which have placed an emphasis on theory. To facilitate this a framework for clinical learning was adapted to guide students' early exposure to clinical practice. The focus was to develop the students' observational and reflective skills whilst also providing the students with a frame of reference within which they could explore their theoretical studies. The information and experiences gained as a result of this study have led to the integration of an Orientation Framework to support students' early clinical experiences in a pre-registration programme.

The Nun study: clinically silent AD, neuronal hypertrophy, and linguistic skills in early life.

PubMed

Iacono, D; Markesbery, W R; Gross, M; Pletnikova, O; Rudow, G; Zandi, P; Troncoso, J C

2009-09-01

It is common to find substantial Alzheimer disease (AD) lesions, i.e., neuritic beta-amyloid plaques and neurofibrillary tangles, in the autopsied brains of elderly subjects with normal cognition assessed shortly before death. We have termed this status asymptomatic AD (ASYMAD). We assessed the morphologic substrate of ASYMAD compared to mild cognitive impairment (MCI) in subjects from the Nun Study. In addition, possible correlations between linguistic abilities in early life and the presence of AD pathology with and without clinical manifestations in late life were considered. Design-based stereology was used to measure the volumes of neuronal cell bodies, nuclei, and nucleoli in the CA1 region of hippocampus (CA1). Four groups of subjects were compared: ASYMAD (n = 10), MCI (n = 5), AD (n = 10), and age-matched controls (n = 13). Linguistic ability assessed in early life was compared among all groups. A significant hypertrophy of the cell bodies (+44.9%), nuclei (+59.7%), and nucleoli (+80.2%) in the CA1 neurons was found in ASYMAD compared with MCI. Similar differences were observed with controls. Furthermore, significant higher idea density scores in early life were observed in controls and ASYMAD group compared to MCI and AD groups. 1) Neuronal hypertrophy may constitute an early cellular response to Alzheimer disease (AD) pathology or reflect compensatory mechanisms that prevent cognitive impairment despite substantial AD lesions; 2) higher idea density scores in early life are associated with intact cognition in late life despite the presence of AD lesions.

Translating Theoretical Principles to Classroom Practice

ERIC Educational Resources Information Center

Robbins, Sheri

2017-01-01

This study followed two teacher candidates from the Communities as Resources in Early Childhood Teacher Education (CREATE) project into their first year classrooms to determine whether they were able to translate the theoretical principles from their teacher preparation program into practice during their first year of teaching. It also examined…

Knowledge translation interventions for critically ill patients: a systematic review*.

PubMed

Sinuff, Tasnim; Muscedere, John; Adhikari, Neill K J; Stelfox, Henry T; Dodek, Peter; Heyland, Daren K; Rubenfeld, Gordon D; Cook, Deborah J; Pinto, Ruxandra; Manoharan, Venika; Currie, Jan; Cahill, Naomi; Friedrich, Jan O; Amaral, Andre; Piquette, Dominique; Scales, Damon C; Dhanani, Sonny; Garland, Allan

2013-11-01

We systematically reviewed ICU-based knowledge translation studies to assess the impact of knowledge translation interventions on processes and outcomes of care. We searched electronic databases (to July, 2010) without language restrictions and hand-searched reference lists of relevant studies and reviews. Two reviewers independently identified randomized controlled trials and observational studies comparing any ICU-based knowledge translation intervention (e.g., protocols, guidelines, and audit and feedback) to management without a knowledge translation intervention. We focused on clinical topics that were addressed in greater than or equal to five studies. Pairs of reviewers abstracted data on the clinical topic, knowledge translation intervention(s), process of care measures, and patient outcomes. For each individual or combination of knowledge translation intervention(s) addressed in greater than or equal to three studies, we summarized each study using median risk ratio for dichotomous and standardized mean difference for continuous process measures. We used random-effects models. Anticipating a small number of randomized controlled trials, our primary meta-analyses included randomized controlled trials and observational studies. In separate sensitivity analyses, we excluded randomized controlled trials and collapsed protocols, guidelines, and bundles into one category of intervention. We conducted meta-analyses for clinical outcomes (ICU and hospital mortality, ventilator-associated pneumonia, duration of mechanical ventilation, and ICU length of stay) related to interventions that were associated with improvements in processes of care. From 11,742 publications, we included 119 investigations (seven randomized controlled trials, 112 observational studies) on nine clinical topics. Interventions that included protocols with or without education improved continuous process measures (seven observational studies and one randomized controlled trial; standardized

Machine Translation-Supported Cross-Language Information Retrieval for a Consumer Health Resource

PubMed Central

Rosemblat, Graciela; Gemoets, Darren; Browne, Allen C.; Tse, Tony

2003-01-01

The U.S. National Institutes of Health, through its National Library of Medicine, developed ClinicalTrials.gov to provide the public with easy access to information on clinical trials on a wide range of conditions or diseases. Only English language information retrieval is currently supported. Given the growing number of Spanish speakers in the U.S. and their increasing use of the Web, we anticipate a significant increase in Spanish-speaking users. This study compares the effectiveness of two common cross-language information retrieval methods using machine translation, query translation versus document translation, using a subset of genuine user queries from ClinicalTrials.gov. Preliminary results conducted with the ClinicalTrials.gov search engine show that in our environment, query translation is statistically significantly better than document translation. We discuss possible reasons for this result and we conclude with suggestions for future work. PMID:14728236

Translational safety biomarkers of colonic barrier integrity in the rat.

PubMed

Erkens, Tim; Bueters, Ruud; van Heerden, Marjolein; Cuyckens, Filip; Vreeken, Rob; Goeminne, Nick; Lammens, Lieve

2018-05-20

The intestinal barrier controls intestinal permeability, and its disruption has been associated with multiple diseases. Therefore, preclinical safety biomarkers monitoring barrier integrity are essential during the development of drugs targeting the intestines, particularly if starting treatment early after onset of disease. Classical toxicology endpoints are not sensitive enough and therefore our objective was to identify non-invasive markers enabling early in vivo detection of colonic barrier perturbation. Male Sprague-Dawley rats were dosed intracolonically via the rectum, using sodium caprate or ibuprofen as tool compounds to alter barrier integrity. Several potentially translational biomarkers and probe molecules related to permeability, inflammation or tissue damage were evaluated, using various analytical platforms, including immunoassays, targeted metabolomics and highly sensitive ultra-performance liquid chromatography-tandem mass spectrometry. Several markers were identified that allow early in vivo detection of colonic barrier integrity changes, before histopathological evidence of tissue damage. The most promising permeability markers identified were plasma fluorescein isothiocyanate-dextran 4000 and a lactulose/mannitol/sucralose mixture in urine. These markers showed maximum increases over 100-fold or approximately 10-50-fold, respectively. Intracolonic administration of the above probe molecules outperformed oral administration and inflammatory or other biomarkers, such as α 2 -macroglobulin, calprotectin, cytokines, prostaglandins and a panel of metabolic molecules to identify early and subtle changes in barrier integrity. However, optimal timing of probe administration and sample collection is important for all markers evaluated. Inclusion of these probe molecules in preclinical toxicity studies might aid in risk assessment and the design of a clinical biomarker plan, as several of these markers have translational potential. Copyright © 2018 John

Synergies and Distinctions between Computational Disciplines in Biomedical Research: Perspective from the Clinical and Translational Science Award Programs

PubMed Central

Bernstam, Elmer V.; Hersh, William R.; Johnson, Stephen B.; Chute, Christopher G.; Nguyen, Hien; Sim, Ida; Nahm, Meredith; Weiner, Mark; Miller, Perry; DiLaura, Robert P.; Overcash, Marc; Lehmann, Harold P.; Eichmann, David; Athey, Brian D.; Scheuermann, Richard H.; Anderson, Nick; Starren, Justin B.; Harris, Paul A.; Smith, Jack W.; Barbour, Ed; Silverstein, Jonathan C.; Krusch, David A.; Nagarajan, Rakesh; Becich, Michael J.

2010-01-01

Clinical and translational research increasingly requires computation. Projects may involve multiple computationally-oriented groups including information technology (IT) professionals, computer scientists and biomedical informaticians. However, many biomedical researchers are not aware of the distinctions among these complementary groups, leading to confusion, delays and sub-optimal results. Although written from the perspective of clinical and translational science award (CTSA) programs within academic medical centers, the paper addresses issues that extend beyond clinical and translational research. The authors describe the complementary but distinct roles of operational IT, research IT, computer science and biomedical informatics using a clinical data warehouse as a running example. In general, IT professionals focus on technology. The authors distinguish between two types of IT groups within academic medical centers: central or administrative IT (supporting the administrative computing needs of large organizations) and research IT (supporting the computing needs of researchers). Computer scientists focus on general issues of computation such as designing faster computers or more efficient algorithms, rather than specific applications. In contrast, informaticians are concerned with data, information and knowledge. Biomedical informaticians draw on a variety of tools, including but not limited to computers, to solve information problems in health care and biomedicine. The paper concludes with recommendations regarding administrative structures that can help to maximize the benefit of computation to biomedical research within academic health centers. PMID:19550198

Masked translation priming effects with low proficient bilinguals.

PubMed

Dimitropoulou, Maria; Duñabeitia, Jon Andoni; Carreiras, Manuel

2011-02-01

Non-cognate masked translation priming lexical decision studies with unbalanced bilinguals suggest that masked translation priming effects are asymmetric as a function of the translation direction (significant effects only in the dominant [L1] to nondominant [L2] language translation direction). However, in contrast to the predictions of most current accounts of masked translation priming effects, bidirectional effects have recently been reported with a group of low proficient bilinguals Duyck & Warlop 2009 (Experimental Psychology 56:173-179). In a series of masked translation priming lexical decision experiments we examined whether the same pattern of effects would emerge with late and low proficient Greek (L1)-Spanish (L2) bilinguals. Contrary to the results obtained by Duyck and Warlop, and in line with the results found in most studies in the masked priming literature, significant translation priming effects emerged only when the bilinguals performed the task with L1 primes and L2 targets. The existence of the masked translation priming asymmetry with low proficient bilinguals suggests that cross-linguistic automatic lexico-semantic links may be established very early in the process of L2 acquisition. These findings could help to define models of bilingualism that consider L2 proficiency level to be a determining factor.

Professional behaviors, sense of belonging, and professional socialization of early career clinical laboratory scientists

NASA Astrophysics Data System (ADS)

Schill, Janna Marie

Professional socialization is a process that individuals experience as members of a profession and consists of the knowledge, attitudes, and experiences that influence and shape their professional identity. The process of professional socialization has not been studied in the clinical laboratory science profession. Clinical laboratory science is an allied health profession that is faced by a workforce shortage that has been caused by a decrease in new graduates, decreased retention of qualified professionals, and increased retirements. Other allied health professions such as nursing, athletic training, and pharmacy have studied professional socialization as a way to identify factors that may influence the retention of early career professionals. This mixed method study, which quantitatively used Hall's Professionalism Scale (1968) in addition to qualitative focus group interviews, sought to identify the professional attitudes and behaviors, sense of belonging, and professional socialization of early career clinical laboratory scientists. Early career clinical laboratory scientists were divided into two groups based upon the amount of work experience they had; new clinical laboratory science graduates have had less than one year of work experience and novice clinical laboratory scientists had between one and three years of work experience. This study found that early career clinical laboratory scientists have established professional identities and view themselves as members of the clinical laboratory science field within four proposed stages of professional socialization consisting of pre-arrival, encounter, adaptation, and commitment. New CLS graduates and novice clinical laboratory scientists were found to be at different stages of the professional stage process. New CLS graduates, who had less than one year of work experience, were found to be in the encounter stage. Novice clinical laboratory scientists, with one to three years of work experience, were found to

Potential clinical translation of juvenile rodent inactivity models to study the onset of childhood obesity.

PubMed

Roberts, Michael D; Company, Joseph M; Brown, Jacob D; Toedebusch, Ryan G; Padilla, Jaume; Jenkins, Nathan T; Laughlin, M Harold; Booth, Frank W

2012-08-01

According to the latest data from the Center for Disease Control and Prevention 17%, or 12.5 million, of children and adolescents aged 2-19 years in the United States are obese. Physical inactivity is designated as one of the actual causes of US deaths and undoubtedly contributes to the obesity epidemic in children and adults. Examining the effects of inactivity on physiological homeostasis during youth is crucial given that 58% of children between the ages 6-11 yr old fail to obtain the recommended 60 min/day of physical activity and 92% of adolescents fail to achieve this goal [Troiano et al. Med Sci Sports Exerc. 40, 2008]. Nonetheless, invasive mechanistic studies in children linking diminished physical activity with metabolic maladies are lacking for obvious ethical reasons. The rodent wheel lock (WL) model was adopted by our laboratory and others to study how different organ systems of juvenile rats respond to a cessation of daily physical activity. Our WL model houses rats in cages equipped with voluntary running wheels starting at 28 days of age. After a certain period of voluntary running (3 to 6 wk), the wheels are locked, thus preventing the rats' primary source of physical activity. The studies discussed herein suggest that obesity-associated maladies including skeletal muscle insulin resistance, hypothalamic leptin resistance, fatty acid oxidation impairments in skeletal muscle and adipose tissue, nonalcoholic fatty liver disease, and endothelial dysfunction are initiated in juvenile animals that are restrained from voluntary exercise via WL. The use of the juvenile rodent WL or other inactivity models will continue to provide a powerful clinical translational tool that can be used for primordial prevention of human childhood obesity.

Escitalopram—translating molecular properties into clinical benefit: reviewing the evidence in major depression

PubMed Central

Leonard, Brian; Taylor, David

2010-01-01

The majority of currently marketed drugs contain a mixture of enantiomers; however, recent evidence suggests that individual enantiomers can have pharmacological properties that differ importantly from enantiomer mixtures. Escitalopram, the S-enantiomer of citalopram, displays markedly different pharmacological activity to the R-enantiomer. This review aims to evaluate whether these differences confer any significant clinical advantage for escitalopram over either citalopram or other frequently used antidepressants. Searches were conducted using PubMed and EMBASE (up to January 2009). Abstracts of the retrieved studies were reviewed independently by both authors for inclusion. Only those studies relating to depression or major depressive disorder were included. The search identified over 250 citations, of which 21 studies and 18 pooled or meta-analyses studies were deemed suitable for inclusion. These studies reveal that escitalopram has some efficacy advantage over citalopram and paroxetine, but no consistent advantage over other selective serotonin reuptake inhibitors. Escitalopram has at least comparable efficacy to available serotonin-norepinephrine reuptake inhibitors, venlafaxine XR and duloxetine, and may offer some tolerability advantages over these agents. This review suggests that the mechanistic advantages of escitalopram over citalopram translate into clinical efficacy advantages. Escitalopram may have a favourable benefit-risk ratio compared with citalopram and possibly with several other antidepressant agents. PMID:20147575

Tissue Engineering of the Urethra: A Systematic Review and Meta-analysis of Preclinical and Clinical Studies.

PubMed

Versteegden, Luuk R M; de Jonge, Paul K J D; IntHout, Joanna; van Kuppevelt, Toin H; Oosterwijk, Egbert; Feitz, Wout F J; de Vries, Rob B M; Daamen, Willeke F

2017-10-01

Urethra repair by tissue engineering has been extensively studied in laboratory animals and patients, but is not routinely used in clinical practice. To systematically investigate preclinical and clinical evidence of the efficacy of tissue engineering for urethra repair in order to stimulate translation of preclinical studies to the clinic. A systematic search strategy was applied in PubMed and EMBASE. Studies were independently screened for relevance by two reviewers, resulting in 80 preclinical and 23 clinical studies of which 63 and 13 were selected for meta-analysis to assess side effects, functionality, and study completion. Analyses for preclinical and clinical studies were performed separately. Full circumferential and inlay procedures were assessed independently. Evaluated parameters included seeding of cells and type of biomaterial. Meta-analysis revealed that cell seeding significantly reduced the probability of encountering side effects in preclinical studies. Remarkably though, cells were only sparsely used in the clinic (4/23 studies) and showed no significant reduction of side effects. ln 21 out of 23 clinical studies, decellularized templates were used, while in preclinical studies other biomaterials showed promising outcomes as well. No direct comparison to current clinical practice could be made due to the limited number of randomized controlled studies. Due to a lack of controlled (pre)clinical studies, the efficacy of tissue engineering for urethra repair could not be determined. Meta-analysis outcome measures were similar to current treatment options described in literature. Surprisingly, it appeared that favorable preclinical results, that is inclusion of cells, were not translated to the clinic. Improved (pre)clinical study designs may enhance clinical translation. We reviewed all available literature on urethral tissue engineering to assess the efficacy in preclinical and clinical studies. We show that improvements to (pre)clinical study

The translational potential of human induced pluripotent stem cells for clinical neurology : The translational potential of hiPSCs in neurology.

PubMed

Devine, Helen; Patani, Rickie

2017-04-01

The induced pluripotent state represents a decade-old Nobel prize-winning discovery. Human-induced pluripotent stem cells (hiPSCs) are generated by the nuclear reprogramming of any somatic cell using a variety of established but evolving methods. This approach offers medical science unparalleled experimental opportunity to model an individual patient's disease "in a dish." HiPSCs permit developmentally rationalized directed differentiation into any cell type, which express donor cell mutation(s) at pathophysiological levels and thus hold considerable potential for disease modeling, drug discovery, and potentially cell-based therapies. This review will focus on the translational potential of hiPSCs in clinical neurology and the importance of integrating this approach with complementary model systems to increase the translational yield of preclinical testing for the benefit of patients. This strategy is particularly important given the expected increase in prevalence of neurodegenerative disease, which poses a major burden to global health over the coming decades.

Objective and quantitative equilibriometric evaluation of individual locomotor behaviour in schizophrenia: Translational and clinical implications.

PubMed

Haralanov, Svetlozar; Haralanova, Evelina; Milushev, Emil; Shkodrova, Diana; Claussen, Claus-Frenz

2018-04-17

Psychiatry is the only medical specialty that lacks clinically applicable biomarkers for objective evaluation of the existing pathology at a single-patient level. On the basis of an original translational equilibriometric method for evaluation of movement patterns, we have introduced in the everyday clinical practice of psychiatry an easy-to-perform computerized objective quantification of the individual locomotor behaviour during execution of the Unterberger stepping test. For the last 20 years, we have gradually collected a large database of more than 1000 schizophrenic patients, their relatives, and matched psychiatric, neurological, and healthy controls via cross-sectional and longitudinal investigations. Comparative analyses revealed transdiagnostic locomotor similarities among schizophrenic patients, high-risk schizotaxic individuals, and neurological patients with multiple sclerosis and cerebellar ataxia, thus suggesting common underlying brain mechanisms. In parallel, intradiagnostic dissimilarities were revealed, which allow to separate out subclinical locomotor subgroups within the diagnostic categories. Prototypical qualitative (dysmetric and ataxic) locomotor abnormalities in schizophrenic patients were differentiated from 2 atypical quantitative ones, manifested as either hypolocomotion or hyperlocomotion. Theoretical analyses suggested that these 3 subtypes of locomotor abnormalities could be conceived as objectively measurable biomarkers of 3 schizophrenic subgroups with dissimilar brain mechanisms, which require different treatment strategies. Analogies with the prominent role of locomotor measures in some well-known animal models of mental disorders advocate for a promising objective translational research in the so far over-subjective field of psychiatry. Distinctions among prototypical, atypical, and diagnostic biomarkers, as well as between neuromotor and psychomotor locomotor abnormalities, are discussed. Conclusions are drawn about the

Core informatics competencies for clinical and translational scientists: what do our customers and collaborators need to know?

PubMed Central

Valenta, Annette L; Meagher, Emma A; Tachinardi, Umberto

2016-01-01

Since the inception of the Clinical and Translational Science Award (CTSA) program in 2006, leaders in education across CTSA sites have been developing and updating core competencies for Clinical and Translational Science (CTS) trainees. By 2009, 14 competency domains, including biomedical informatics, had been identified and published. Since that time, the evolution of the CTSA program, changes in the practice of CTS, the rapid adoption of electronic health records (EHRs), the growth of biomedical informatics, the explosion of big data, and the realization that some of the competencies had proven to be difficult to apply in practice have made it clear that the competencies should be updated. This paper describes the process undertaken and puts forth a new set of competencies that has been recently endorsed by the Clinical Research Informatics Workgroup of AMIA. In addition to providing context and background for the current version of the competencies, we hope this will serve as a model for revision of competencies over time. PMID:27121608

Clinical significance of early smoking withdrawal effects and their relationships with nicotine metabolism: preliminary results from a pilot study.

PubMed

Hendricks, Peter S; Delucchi, Kevin L; Benowitz, Neal L; Hall, Sharon M

2014-05-01

Although the early time course of smoking withdrawal effects has been characterized, the clinical significance of early withdrawal symptoms and their predictors are unknown. This study evaluated the relationships of early smoking withdrawal effects with quit attempt outcomes and the rate of nicotine metabolism. Eleven treatment-seeking smokers abstained from smoking for 4 hr in the laboratory before a quit attempt. Withdrawal measures included heart rate, sustained attention, and self-report. Following baseline assessment, withdrawal measures were administered every 30 min. At the conclusion of the 4-hr early withdrawal session, participants received a brief smoking cessation intervention and then returned 1 week and 12 weeks later for outcome assessments that included biochemically confirmed smoking abstinence, cigarettes smoked in the past 24hr, and self-reported withdrawal symptoms. The rate of nicotine metabolism was estimated at intake with the nicotine metabolite ratio (trans-3'-hydroxycotinine/cotinine) measured in saliva. Greater self-reported negative affect and concentration difficulty during early withdrawal, most notably anxiety, were related with poorer quit attempt outcomes. There was some indication that although a faster increase in craving and greater hunger during early withdrawal were associated with more favorable outcomes, a greater decrease in heart rate during this time was associated with poorer outcomes. Faster nicotine metabolism was related to a faster increase in anxiety but a slower increase in craving during early withdrawal. These findings lend support to the clinical significance of early smoking withdrawal effects. The rate of nicotine metabolism may be a useful predictor of early withdrawal symptoms.

Dementia, Preclinical Studies in Neurodegeneration and its Potential for Translational Medicine in South America

PubMed Central

Cardona-Gómez, Gloria Patricia; Lopera, Francisco

2016-01-01

Latin-American people with dementia will increase to an astounding 368% in 2050, higher than USA and Europe. In addition, to sporadic dementia type like Alzheimer, and vascular dementia (VaD) progression after Cerebrovascular disease is also found. These incidences are increased in Colombia by specific populations affected with pure Neurodegenerative and VaDs like Autosomical Dominant familial Alzheimer’s disease (AD) and Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). In spite of the enormous human effort with and economical effort and investment costs, neither sporadic nor genetic kinds of dementia progression have been prevented or blocked yet. Currently, there exist several animal models that partially solve the understanding of the neurodegenerative etiopathogenesis and its treatment. However, when the potential therapies are translated to humans, those do not work or present a limited action. Main difficulties are the diverse comorbility associated to the cause and/or several affected brain regions, reducing the efficacy of some therapies which are limited to a tissue-specific action or modulating a kind of neurotransmission. Global investigation suggests that a general prevention could be achieved with the improvement in the quality of lifestyle, including healthy diet, physical and mental activity, and avoiding mechanical or chemical pro-inflammatory events in an early stage in the most of non-communicable diseases. In this review article, we present some molecular targets and preclinical studies in animal models to propose strategies that could be useful in a future translation to prevent or block neurodegeneration: one is gene therapy; silencing pathogenic genes in critical brain areas where excitotoxicity arise and spread. Another is to take advantage of the natural source and its wide biodiversity of natural products that are capable of identifying, by the blocking and prevention of

National Institutes of Health Update: Translating Basic Behavioral Science into New Pediatric Obesity Interventions.

PubMed

Czajkowski, Susan M

2016-06-01

Pediatric obesity increases the risk of later-life obesity and chronic diseases. Basic research to better understand factors associated with excessive weight gain in early life and studies translating research findings into preventive and therapeutic strategies are essential to our ability to better prevent and treat childhood obesity. This overview describes several National Institutes of Health efforts designed to stimulate basic and translational research in childhood obesity prevention and treatment. These examples demonstrate the value of research in early phase translational pediatric obesity research and highlight some promising directions for this important area of research. Published by Elsevier Inc.

75 FR 81611 - Submission for OMB Review; Comment Request; National Evaluation of the Clinical and Translational...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-28

... Patricia Newman, Program Analyst, Office of Science Policy, National Center for Research Resources, 6701...: December 20, 2010. Meryl Sufian, Supervisory Health Science Policy Analyst, Office of Science Policy, NCRR... Evaluation of the Clinical and Translational Science Awards (CTSA) Initiative SUMMARY: Under the provisions...

Behavioral and electrophysiological signatures of word translation processes.

PubMed

Jost, Lea B; Radman, Narges; Buetler, Karin A; Annoni, Jean-Marie

2018-01-31

Translation is a demanding process during which a message is analyzed, translated and communicated from one language to another. Despite numerous studies on translation mechanisms, the electrophysiological processes underlying translation with overt production remain largely unexplored. Here, we investigated how behavioral response patterns and spatial-temporal brain dynamics differ in a translation compared to a control within-language word-generation task. We also investigated how forward and backward translation differs on the behavioral and electrophysiological level. To address these questions, healthy late bilingual subjects performed a translation and a within-language control task while a 128-channel EEG was recorded. Behavioral data showed faster responses for translation compared to within-language word generation and faster responses for backward than forward translation. The ERP-analysis revealed stronger early ( < 200ms) preparatory and attentional processes for between than within word generation. Later (424-630ms) differences were characterized by distinct engagement of domain-general control networks, namely self-monitoring and lexical access interference. Language asymmetry effects occurred at a later stage (600ms), reflecting differences in conceptual processing characterized by a larger involvement of areas implicated in attention, arousal and awareness for forward versus backward translation. Copyright © 2017 Elsevier Ltd. All rights reserved.