NIH Roadmap Research Articles

BioPortal: enhanced functionality via new Web services from the National Center for Biomedical Ontology to access and use ontologies in software applications

The National Center for Biomedical Ontology (NCBO) is one of the National Centers for Biomedical Computing funded under the NIH Roadmap Initiative. Contributing to the national computing infrastructure, NCBO has developed BioPortal, a web portal that provides access to a library of biomedical ontologies and terminologies (http://bioportal.bioontology.org) via the NCBO Web services. BioPortal enables community participation in the evaluation and evolution of ontology content by providing features to add mappings between terms, to add comments linked to specific ontology terms and to provide ontology reviews. The NCBO Web services (http://www.bioontology.org/wiki/index.php/NCBO_REST_services) enable this functionality and provide a uniform mechanism to access ontologies from a variety of knowledge representation formats, such as Web Ontology Language (OWL) and Open Biological and Biomedical Ontologies (OBO) format. The Web services provide multi-layered access to the ontology content, from getting all terms in an ontology to retrieving metadata about a term. Users can easily incorporate the NCBO Web services into software applications to generate semantically aware applications and to facilitate structured data collection.

The NIH Roadmap: An Opportunity for Occupational Therapy

The NIH Roadmap: An Opportunity for Occupational Therapy

Initial Evaluation of the Pediatric PROMIS Health Domains In Children and Adolescents with Sickle Cell Disease (SCD).

AbstractAbstract 3829The Patient-Reported Outcomes Measurement Information System (PROMIS) project was developed to advance the science and application of patient-reported outcomes (PRO) associated with chronic diseases, and is supported as a trans-NIH initiative as part of the NIH Roadmap for Medical Research. One main PROMIS goal is to develop a set of item banks and computerized adaptive tests (CAT) that could be used by the clinical research community for clinical trials or health outcome studies. The PROMIS pediatric project is developing self-report PRO for youths aged 8–17 years across several health domains that are important across a variety of illnesses, including physical function, pain, fatigue, emotional distress, and social function. In addition to validation in a large sample of healthy children, these measures are being validated in a variety of pediatric chronic illnesses, including sickle cell disease (SCD). We hypothesized that the pediatric PROMIS measure would be sensitive to changes in health status of children with SCD. A one-time cross-sectional study was conducted of the pediatric PROMIS item banks in children with SCD. A convenience sample of SCD patients aged 8–17 years followed at 2 large Sickle Cell programs (Emory University and Duke University) was recruited from routine clinic visits. Individuals were eligible to participate if they could speak and read English and were able to complete a computer administered survey. Children completed the pediatric PROMIS survey over the internet using a computer adapted testing (CAT) protocol on the PROMIS Assessment Center secure website. Children were supervised by the research staff to ensure that the responses were self-reported. Parents also completed a short demographics questionnaire, and medical related information was verified from medical records. A total of 236 subjects (mean age 12.49 ± 2.82, 49.8% female) participated in the study (Emory 170, Duke 66) over an 8 month period from May 2009 to January 2010. Most participants had an SS genotype (76.5%), while 16.7% had SC, 4.7% had Sickle B+thalassemia, and 1.3% had Sickle B0 thalassemia. At the time of the study 19.1% were receiving chronic transfusions and 45.5% were taking hydroxyurea. In the prior 6 months, participants reported a mean (SD) of 4.93±9.08 home-managed painful episodes; 1.21±2.91 ED managed painful episodes; and 0.72±1.71 hospitalizations. Parents reported daily analgesic usage by 35%, and 17.1% with hip or joint problems. Scores on the pain interference domain increased with increasing age (r = .175, p=.007). Correlations between age and all other domains were not significant. Physical function dexterity and mobility, depression, pain interference, tired, and low energy domain scores were reduced in children with a reported hip or joint problem compared to for those without hip or joint problems (all p<.05). The occurrence of pain at home requiring treatment in the previous 7 days was associated with declines in functioning in the following domains: depression, anxiety, pain interference, fatigue, low energy, dexterity, and mobility (all p<0.01). Similarly, the number of pain episodes managed at home in the past 6 months was positively correlated with the following domains: pain interference (r = .21, p < .002), depression (r=-.6, p=.01), tired (r=-.26, p<.001), low energy (r=.17, p=.03), and mobility (r=-.23, p=.004). Initial evaluation of the the pediatric PROMIS item banks indicate that self-reported health domains vary with overall clinical severity and frequency of recent clinical events. Current longitudinal studies with these measures at the Emory Sickle Cell Consortium are designed to determine their sensitivity to specific clinical events (hospitalized painful episodes) and related minimally significant differences. These results suggest that the PROMIS pediatric measures should be considered for use in future pediatric SCD clinical trials. Supported by NIH U01-AR052181. Disclosures:Dampier:Anthera Pharmaceuticals Inc: Chair DSMB; Glycomimetics Inc: Chair DSMB.

Open Access High Throughput Drug Discovery in the Public Domain: A Mount Everest in the Making

High throughput screening (HTS) facilitates screening large numbers of compounds against a biochemical target of interest using validated biological or biophysical assays. In recent years, a significant number of drugs in clinical trails originated from HTS campaigns, validating HTS as a bona fide mechanism for hit finding. In the current drug discovery landscape, the pharmaceutical industry is embracing open innovation strategies with academia to maximize their research capabilities and to feed their drug discovery pipeline. The goals of academic research have therefore expanded from target identification and validation to probe discovery, chemical genomics, and compound library screening. This trend is reflected in the emergence of HTS centers in the public domain over the past decade, ranging in size from modestly equipped academic screening centers to well endowed Molecular Libraries Probe Centers Network (MLPCN) centers funded by the NIH Roadmap initiative. These centers facilitate a comprehensive approach to probe discovery in academia and utilize both classical and cutting-edge assay technologies for executing primary and secondary screening campaigns. The various facets of academic HTS centers as well as their implications on technology transfer and drug discovery are discussed, and a roadmap for successful drug discovery in the public domain is presented. New lead discovery against therapeutic targets, especially those involving the rare and neglected diseases, is indeed a Mount Everestonian size task, and requires diligent implementation of pharmaceutical industry's best practices for a successful outcome.

Methodological Issues in Child Welfare and Children’s Mental Health Implementation Research

Methodological Issues in Child Welfare and Children’s Mental Health Implementation Research

Ask A Biologist: Bringing Science to the Public

Ask A Biologist: Bringing Science to the Public

The NIH Roadmap Epigenomics Mapping Consortium

The NIH Roadmap Epigenomics Mapping Consortium aims to produce a public resource of epigenomic maps for stem cells and primary ex vivo tissues selected to represent the normal counterparts of tissues and organ systems frequently involved in human disease.

Application of machine learning methods to histone methylation ChIP-Seq data reveals H4R3me2 globally represses gene expression

BackgroundIn the last decade, biochemical studies have revealed that epigenetic modifications including histone modifications, histone variants and DNA methylation form a complex network that regulate the state of chromatin and processes that depend on it including transcription and DNA replication. Currently, a large number of these epigenetic modifications are being mapped in a variety of cell lines at different stages of development using high throughput sequencing by members of the ENCODE consortium, the NIH Roadmap Epigenomics Program and the Human Epigenome Project. An extremely promising and underexplored area of research is the application of machine learning methods, which are designed to construct predictive network models, to these large-scale epigenomic data sets.ResultsUsing a ChIP-Seq data set of 20 histone lysine and arginine methylations and histone variant H2A.Z in human CD4+ T-cells, we built predictive models of gene expression as a function of histone modification/variant levels using Multilinear (ML) Regression and Multivariate Adaptive Regression Splines (MARS). Along with extensive crosstalk among the 20 histone methylations, we found H4R3me2 was the most and second most globally repressive histone methylation among the 20 studied in the ML and MARS models, respectively. In support of our finding, a number of experimental studies show that PRMT5-catalyzed symmetric dimethylation of H4R3 is associated with repression of gene expression. This includes a recent study, which demonstrated that H4R3me2 is required for DNMT3A-mediated DNA methylation--a known global repressor of gene expression.ConclusionIn stark contrast to univariate analysis of the relationship between H4R3me2 and gene expression levels, our study showed that the regulatory role of some modifications like H4R3me2 is masked by confounding variables, but can be elucidated by multivariate/systems-level approaches.

Proceedings of the University of Pennsylvania Annual Conference on Statistical Issues in Clinical Trials: Early, translational and proof of concept studies: The ‘Go/No Go’ Decisions

Proceedings of the University of Pennsylvania Annual Conference on Statistical Issues in Clinical Trials: Early, translational and proof of concept studies: The ‘Go/No Go’ Decisions

Maximizing Team Mentoring for Empowering Success in Multidisciplinary Research and Career Development

The integration of basic, clinical and translational research has required new approaches to complex problem solving in neurosciences and other discipline. Often colleagues and trainees with very diverse expertise are needed to come together and share their unique vantage points to develop unique solutions to complex questions – what is now known as “team science”. Yet few basic and clinical investigators have been prepared in their training to work in this collaborative manner – and one that will be essential toward a wide distribution of new knowledge and improved clinical practice via translational research approaches. With support from the NIH Roadmap Initiative and the Clinical Science and Translational Award at the Clinical and Translational Science Institute at the University of Pittsburgh, we have developed a comprehensive program for mentoring trainees, including graduate students, postdocs, clinical fellows and junior faculty to help maximize their unique group of mentors who bring the necessary multidisciplinary perspectives to the research investigation at hand. This presentation will provide an overview of some of the elements that contribute to this new model of preparing individuals for success with team mentoring including 1) definitions of the roles of mentee and mentors, 2) the use of annual contracts to affirm commitment to the process, 3) the approaches and strategies used to train both mentees and mentors to ensure a successful launch of a new team, 4) approaches for monitoring, advising, adjusting and/or terminating mentoring relationships, if needed, and 5) strategies to keep the process focused on the mentee's career goals in clinical and translational research – typically a unique path that will differ from the path of the more experienced mentors.

Translational research queries, fascia research congress sequels, and beyond....

Translational research queries, fascia research congress sequels, and beyond....

Serving the enterprise and beyond with informatics for integrating biology and the bedside (i2b2)

Informatics for Integrating Biology and the Bedside (i2b2) is one of seven projects sponsored by the NIH Roadmap National Centers for Biomedical Computing (http://www.ncbcs.org). Its mission is to provide clinical investigators with the tools necessary to integrate medical record and clinical research data in the genomics age, a software suite to construct and integrate the modern clinical research chart. i2b2 software may be used by an enterprise's research community to find sets of interesting patients from electronic patient medical record data, while preserving patient privacy through a query tool interface. Project-specific mini-databases ("data marts") can be created from these sets to make highly detailed data available on these specific patients to the investigators on the i2b2 platform, as reviewed and restricted by the Institutional Review Board. The current version of this software has been released into the public domain and is available at the URL: http://www.i2b2.org/software.

Parallel Synthesis of An Oligomeric Imidazole-4,5-dicarboxamide Library

A library of oligomeric compounds was synthesized based on the imidazole-4,5-dicarboxylic acid scaffold along with amino acid esters and chiral diamines derived from amino acids. The final compounds incorporate nonpolar amino acids (Leu, Phe, Trp), polar amino acids (Ser, Asp, Arg), and neutral amino acids (Gly, Ala), and were designed to be useful in screening for inhibitors of protein-protein interactions. Many of the protected and deprotected oligomers show evidence of conformational isomers persistent at room temperature in aqueous solution. A total of 317 final oligomers, out of 441 targeted compounds, were obtained in high analytical purity and of sufficient quantity to submit them for high-throughput screening as part of the NIH Roadmap.

White Paper on CTSA Consortium Role in Facilitating Comparative Effectiveness Research

Background Appreciating the need to better translate biomedical research into improved clinical care and health, the NIH Roadmap was initiated in 2003 to focus on this by strengthening NIH’s central role in clinical research and clinical research training. As part of the needed re-engineering, in 2006 NIH began the CTSA program. At this writing (Summer 2009), there are 39 CTSAs at leading universities across the United States, each having a clinical research graduate program and extensive resources for promoting clinical and translational research. Each of these, and the CTSA Consortium as a whole, are committed to transforming clinical and translational research to maximize impact on health. The CTSAs bring to this challenge an array of capacities, extensive research infrastructure, formal training and career development programs, community engagement of the public and of clinical practice communities, and informatics related to research and clinical practice. Various CTSAs have different areas of emphasis, including along the spectrum of translational research from bench to patient bedside (the first translational step, “T1”), from the bedside to general use in clinical practice (“T2”), and from clinical practice to public benefit and policy (“T3”). This broad array of activities has allowed the national consortium to be responsive to needs all along this path of translation of biomedical research into practice and public benefit. Although the activities of CER can be seen as primarily involving T2 and T3 research, they also can be seen as focusing on the optimal translation of T1 research into effective treatment, and thus the very epitome of work in which CTSAs should be deeply involved. This appreciation was reinforced by CER’s selection as a key Strategic Goal focus of the CTSA Consortium. In this context, the CER Strategic Goal of the CTSA Consortium is to promote the translation of the results of clinical and translational research into practice and public policy. In service of this, in two sections below, we review the span of CER resources across the CTSA Consortium and propose potential roles for CTSAs in supporting CER. As a point of reference for this White Paper, below are two important definitions of CER from reports released at the end of June 2009, from the IOM and from the FCC-CER: Definition from the IOM Report on Priorities for CER The generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition or to improve the delivery of care. The purpose of CER is to assist patients, clinicians, purchasers, and policy makers, and the public to make informed decisions that will improve healthcare at both the individual and population levels.

Interdisciplinary Teams and the Road to Discovery

HomeRadiologyVol. 254, No. 1 PreviousNext REVIEWS AND COMMENTARYPERSPECTIVESInterdisciplinary Teams and the Road to DiscoveryJonathan S. Lewin Jonathan S. Lewin Author Affiliations1From the Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 601 N Caroline St, Suite 4210, Baltimore, MD 21287.Address correspondence to the author (e-mail: [email protected]).Jonathan S. Lewin Published Online:Dec 14 2009https://doi.org/10.1148/radiol.09091395MoreSectionsFull textPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In AbstractThe development and efforts of interdisciplinary research teams hold great promise for the future of our field, and with some forethought and insight, these teams may represent the most powerful pathway toward the next generation of advances in imaging and imaging-guided intervention.© RSNA, 2010References1 Surowiecki J. The wisdom of crowds. New York, NY: Random House Publishers, 2004. Google Scholar2 National Institutes of Health. NIH roadmap: Interdisciplinary Research Centers Workshop, Bethesda, Md, February 9–10, 2006. Google Scholar3 National Institutes of Health. NIH roadmap for medical research: research teams of the future—NIH backgrounder. Bethesda, Md: National Institutes of Health, 2005; 9. Google Scholar4 Bennis W, Biederman PW. Organizing genius: the secrets of creative collaboration. Cambridge, Mass: Perseus, 1997. Google Scholar5 Collins JC, Porras JI. Building your company’s vision. Harv Bus Rev 1996;65–77. Google Scholar6 Collins JC, Porras JI. Built to last: successful habits of visionary companies. New York, NY: Harper Collins, 1994. Google Scholar7 Halushka PV, Krug EL. Is the training of biomedical scientists at a crossroads?. Acad Med 2009;84(4):421–423. Crossref, Medline, Google Scholar8 Straus SE, Chatur F, Taylor M. Issues in the mentor-mentee relationship in academic medicine: a qualitative study. Acad Med 2009;84(1):135–139. Crossref, Medline, Google Scholar9 Lee JM, Anzai Y, Langlotz CP. Mentoring the mentors: aligning mentor and mentee expectations. Acad Radiol 2006;13(5):556–561. Crossref, Medline, Google Scholar10 Berk RA, Berg J, Mortimer R, Walton-Moss B, Yeo TP. Measuring the effectiveness of faculty mentoring relationships. Acad Med 2005;80(1):66–71. Crossref, Medline, Google Scholar11 Zerzan JT, Hess R, Schur E, Phillips RS, Rigotti N. Making the most of mentors: a guide for mentees. Acad Med 2009;84(1):140–144. Crossref, Medline, Google ScholarArticle HistoryReceived July 29, 2009; Revision requested July 30; revision received August 23; final version accepted August 24.Published online: Dec 14 2009Published in print: Jan 2010 FiguresReferencesRelatedDetailsCited ByContinuing to Thrive in Academic Radiology Despite Decreasing ReimbursementSunilJeph, KathleenGundry, JonathonMaffie, Jonathan G.Martin, Gloria J. GuzmanPerez-Carrillo, Bradley M.Spieler, Prabhakar ShanthaRajiah2023 | Current Problems in Diagnostic Radiology, Vol. 52, No. 1Team Science: A Practical Approach to Starting Collaborative ProjectsMiral MPatel, Tanya WMoseley, Emily SNia, FrancesPerez, Megha MKapoor, Gary JWhitman2021 | Journal of Breast Imaging, Vol. 3, No. 6Human and social capital determinants of translational activity in medical sciencesKyungWooKim, Eric W.Welch, TimothyJohnson2017 | Science and Public PolicyEffectiveness of quality improvement interventions for patient safety in radiologyShafiqur RahmanJabin, TimSchultz, PeterHibbert, CatherineMandel, WilliamRunciman2016 | JBI Database of Systematic Reviews and Implementation Reports, Vol. 14, No. 9Cultures of Interdisciplinary Teams: How to Foster Good DynamicsJeanieYoungwerth, MarthaTwaddle2011 | Journal of Palliative Medicine, Vol. 14, No. 5Recommended Articles Creating Value through Incremental Innovation: Managing Culture, Structure, and ProcessRadiology2018Volume: 288Issue: 2pp. 330-340Optimizing Performance by Preventing Disruptive Behavior in RadiologyRadioGraphics2018Volume: 38Issue: 6pp. 1639-1650Increasing Median Time between Interruptions in a Busy Reading RoomRadioGraphics2021Volume: 41Issue: 2pp. E47-E56The Road to Wellness: Engagement Strategies to Help Radiologists Achieve Joy at WorkRadioGraphics2018Volume: 38Issue: 6pp. 1651-1664External Factors That Influence the Practice of Radiology: Proceedings of the International Society for Strategic Studies in Radiology MeetingRadiology2017Volume: 283Issue: 3pp. 845-853See More RSNA Education Exhibits Quantitative Imaging with CT: A Comprehensive ReviewDigital Posters2019Optimizing the Mentor-Mentee Relationship: A Guide for MenteesDigital Posters2019Utilization of Imaging in Clinical Trials Under Current FDA GuidelinesDigital Posters2020 RSNA Case Collection Subclavian Stenosis with Pre-StealRSNA Case Collection2021Ingested Button Battery RSNA Case Collection2021Right Middle Lobe Congenital Lobar Overinflation (CLO)RSNA Case Collection2020 Vol. 254, No. 1 Metrics Altmetric Score PDF download

An integrated service for Personalised Healthcare and Wellness (PHW)

At the Systems Biology Lab of the University of Florida, we are developing an integrated system, PHW service, for accessing and storing and monitoring information in personalised medicine. We intend to take a practical approach to build such a system in the framework of clinical and translational sciences of the NIH Roadmap.

Participation in investigational fertility preservation research: a feminist research ethics approach.

The goals and rhetoric of The Oncofertility Consortium (National Institutes of Health. NIH Roadmap for Medical Research. Funded Research: Interdisciplinary Research, Interdisciplinary Research Consortium. http://nihroadmap.nih.gov/interdisciplinary/fundedresearch.asp. Accessed August 25, 2009) are aimed toward preserving cancer patients’ reproductive choices and facilitating their reproductive autonomy after cancer. While the end goals of oncofertility research are oriented toward safeguarding the possibility of biological reproduction for women and girls facing cancer treatments that may affect their fertility, considerable basic and clinical research is still needed in order for oocyte cryopreservation, in vitro follicle maturation, and ovarian tissue cryopreservation to become established fertility preservation techniques. From a feminist research ethics perspective, ethical standards for conducting both basic and clinical research must not only include but also go beyond ensuring institutional review board approval of human subjects research and collating evidence of safety and efficacy. To proceed with fertility preservation research in an ethical and just manner, it is also important to ask (1) on whose bodies is fertility preservation research dependant and (2) in selecting research subject populations, how should researchers balance the risks and benefits to prospective participants? This chapter applies a feminist research ethics approach to the oncofertility context, with a particular focus on the sources of oocytes and ovarian tissue for investigational fertility preservation research and the potential vulnerabilities of participating in this research.

The NIH Human Microbiome Project

The Human Microbiome Project (HMP), funded as an initiative of the NIH Roadmap for Biomedical Research (http://nihroadmap.nih.gov), is a multi-component community resource. The goals of the HMP are: (1) to take advantage of new, high-throughput technologies to characterize the human microbiome more fully by studying samples from multiple body sites from each of at least 250 "normal" volunteers; (2) to determine whether there are associations between changes in the microbiome and health/disease by studying several different medical conditions; and (3) to provide both a standardized data resource and new technological approaches to enable such studies to be undertaken broadly in the scientific community. The ethical, legal, and social implications of such research are being systematically studied as well. The ultimate objective of the HMP is to demonstrate that there are opportunities to improve human health through monitoring or manipulation of the human microbiome. The history and implementation of this new program are described here.

Cardiovascular Disease Surveillance in the Comparative Effectiveness Landscape

As the leading cause of death in the Western world, cardiovascular disease (CVD) constitutes an enormous public health problem.1 The last 4 decades have been characterized chiefly by the postponement of CVD events and CVD related deaths until older age. Thus, the burden of CVD is increasing in parallel with the increase in life expectancy.2 Within this context, identifying persons with CVD, measuring its incidence and outcome and how these vary over time and across populations is essential. A central goal of this monitoring (otherwise termed surveillance) has been to understand the determinants of the trends in CVD and in particular the respective responsibility of primary prevention versus that of the care of established disease in the genesis of the CVD trends. A direct extension of surveillance is its application to assess the effectiveness of care and the response to interventions designed to improve the quality of care. Articles see pp 414, 475, and 508 Over the first year of its existence, the journal Circulation: Cardiovascular Quality and Outcomes published 3 important articles that illustrate the clinical relevance of surveillance and the applicability of trend studies to care improvement. The article by Lewsey et al constitutes a classic example of CVD surveillance.3 The authors present much needed data on recent (1986 to 2005) trends in the epidemiology of stroke indicating that age- and sex-specific incidence rates of fatal and nonfatal hospitalized strokes in Scotland declined in men from 235 (95% CI, 229 to 242) to 149 (144 to 154) and in women from 299 (292 to 306) to 182 (177 to 188). The decline in incidence of hospitalized stroke varied by age, but overall this equated to a relative reduction in the risk of stroke of 31% in men and 42% in women. Declines in the …

Small-Molecule Modulators of the NF-&amp;#954;B Pathway Newly Identified by a Translocation-Based Cellular Assay

Nuclear factor kappa B (NF-kappaB) is an important transcription factor. Aberrant regulation of the NF-kappaB pathway is frequently observed in a number of major ailments such as cancer and inflammatory diseases. Hence NF-kappaB modulators have been intensely pursued for their potential therapeutic applications. Numerous reviews have described recent progress in the development of these agents. More recently, a variety of structurally and functionally novel small molecules, identified through high-throughput screens conducted within the Molecular Libraries Screening Center Network (MLSCN) of the NIH Roadmap for Medical Research, have been added to the current list of NF-kappaB regulators. This review will discuss the inhibitors and activators newly discovered by Columbia's Molecular Libraries Screening Center (MLSC) using a well-designed and stable cellular assay.