The impact of greyscale inversion for nodule detection in an anthropomorphic chest phantom: a free-response observer study

Objective: The aim of this work was to assess the impact of greyscale inversion on nodule detection on poster- oanterior chest X-ray images. Previous work has attemp- ted this, with no consensus opinion formed. We assessed the value of “fast-flicking” between standard and inverted display modes for nodule detection. Methods: Six consultant radiologists (with 5–32 years’ reporting experience) completed an observer task under the free-response paradigm. An anthropomorphic chest phantom was loaded with 50 different configurations of simulated nodules (1–4 nodules per case) measuring 5, 8, 10 and 12mm in spherical diameter; each configuration represented a single case. In addition, 25 cases contained no nodules. Images were displayed in three modes: (i) standard, (ii) inverted and (iii) fast-flicking between standard and inverted display modes. Each observer completed the study in a different order of display (i, ii, iii) using a calibrated 5-megapixel monitor. Nodules were localized with mouse clicks and ratings assigned using a 1–10 discrete slider-bar confidence scale. Rjafroc (Pitts- burgh, PA) was used for data analysis; differences in nodule detection performance were considered significant at 0.05. Results: The observer-averaged weighted jackknife alter- native free-response receiver-operating characteristic figures of merit were 0.715 (standard), 0.684 (inverted) and 0.717 (fast-flicking). Random-reader fixed-case anal- ysis revealed no statistically significant difference be- tween any treatment pair [F(2,8) 5 1.22; p 5 0.345]. Conclusion: No statistically significant difference in nodule detection was found for the three display conditions. Advances in knowledge: We have investigated the impact of fast-flicking between standard and inverted display modes for the detection of nodules. We found no benefit

Evaluating the informatics for integrating biology and the bedside system for clinical research

<p>Abstract</p> <p>Background</p> <p>Selecting patient cohorts is a critical, iterative, and often time-consuming aspect of studies involving human subjects; informatics tools for helping streamline the process have been identified as important infrastructure components for enabling clinical and translational research. We describe the evaluation of a free and open source cohort selection tool from the Informatics for Integrating Biology and the Bedside (i2b2) group: the i2b2 hive.</p> <p>Methods</p> <p>Our evaluation included the usability and functionality of the i2b2 hive using several real world examples of research data requests received electronically at the University of Utah Health Sciences Center between 2006 - 2008. The hive server component and the visual query tool application were evaluated for their suitability as a cohort selection tool on the basis of the types of data elements requested, as well as the effort required to fulfill each research data request using the i2b2 hive alone.</p> <p>Results</p> <p>We found the i2b2 hive to be suitable for obtaining estimates of cohort sizes and generating research cohorts based on simple inclusion/exclusion criteria, which consisted of about 44% of the clinical research data requests sampled at our institution. Data requests that relied on post-coordinated clinical concepts, aggregate values of clinical findings, or temporal conditions in their inclusion/exclusion criteria could not be fulfilled using the i2b2 hive alone, and required one or more intermediate data steps in the form of pre- or post-processing, modifications to the hive metadata, etc.</p> <p>Conclusion</p> <p>The i2b2 hive was found to be a useful cohort-selection tool for fulfilling common types of requests for research data, and especially in the estimation of initial cohort sizes. For another institution that might want to use the i2b2 hive for clinical research, we recommend that the institution would need to have structured, coded clinical data and metadata available that can be transformed to fit the logical data models of the i2b2 hive, strategies for extracting relevant clinical data from source systems, and the ability to perform substantial pre- and post-processing of these data.</p

The Role of Quantitative Pharmacology in an Academic Translational Research Environment

Translational research is generally described as the application of basic science discoveries to the treatment or prevention of disease or injury. Its value is usually determined based on the likelihood that exploratory or developmental research can yield effective therapies. While the pharmaceutical industry has evolved into a highly specialized sector engaged in translational research, the academic medical research community has similarly embraced this paradigm largely through the motivation of the National Institute of Health (NIH) via its Roadmap initiative. The Clinical and Translational Science Award (CTSA) has created opportunities for institutions which can provide the multidisciplinary environment required to engage such research. A key component of the CTSA and an element of both the NIH Roadmap and the FDA Critical Path is the bridging of bench and bedside science via quantitative pharmacologic relationships. The infrastructure of the University of Pennsylvania/Children’s Hospital of Philadelphia CTSA is highlighted relative to both research and educational objectives reliant upon quantitative pharmacology. A case study, NIH-sponsored research program exploring NK1r antagonism for the treatment NeuroAIDS is used to illustrate the application of quantitative pharmacology in a translational research paradigm

Reengineering the clinical research enterprise to involve more community clinicians

<p>Abstract</p> <p>Background</p> <p>The National Institutes of Health has called for expansion of practice-based research to improve the clinical research enterprise.</p> <p>Methods</p> <p>This paper presents a model for the reorganization of clinical research to foster long-term participation by community clinicians.</p> <p>Based on the literature and interviews with clinicians and other stakeholders, we posited a model, conducted further interviews to test the viability of the model, and further adapted it.</p> <p>Results</p> <p>We propose a three-dimensional system of checks and balances to support community clinicians using research support organizations, community outreach, a web-based registry of clinicians and studies, web-based training services, quality audits, and a feedback mechanism for clinicians engaged in research.</p> <p>Conclusions</p> <p>The proposed model is designed to offer a systemic mechanism to address current barriers that prevent clinicians from participation in research. Transparent mechanisms to guarantee the safety of patients and the integrity of the research enterprise paired with efficiencies and economies of scale are maintained by centralizing some of the functions. Assigning other responsibilities to more local levels assures flexibility with respect to the size of the clinician networks and the changing needs of researchers.</p

Collaborative research between clinicians and researchers: a multiple case study of implementation

<p>Abstract</p> <p>Background</p> <p>Bottom-up, clinician-conceived and directed clinical intervention research, coupled with collaboration from researcher experts, is conceptually endorsed by the participatory research movement. This report presents the findings of an evaluation of a program in the Veterans Health Administration meant to encourage clinician-driven research by providing resources believed to be critical. The evaluation focused on the extent to which funded projects: maintained integrity to their original proposals; were methodologically rigorous; were characterized by collaboration between partners; and resulted in sustained clinical impact.</p> <p>Methods</p> <p>Researchers used quantitative (survey and archival) and qualitative (focus group) data to evaluate the implementation, evaluation, and sustainability of four clinical demonstration projects at four sites. Fourteen research center mentors and seventeen clinician researchers evaluated the level of collaboration using a six-dimensional model of participatory research.</p> <p>Results</p> <p>Results yielded mixed findings. Qualitative and quantitative data suggested that although the process was collaborative, clinicians' prior research experience was critical to the quality of the projects. Several challenges were common across sites, including subject recruitment, administrative support and logistics, and subsequent dissemination. Only one intervention achieved lasting clinical effect beyond the active project period. Qualitative analyses identified barriers and facilitators and suggested areas to improve sustainability.</p> <p>Conclusions</p> <p>Evaluation results suggest that this participatory research venture was successful in achieving clinician-directed collaboration, but did not produce sustainable interventions due to such implementation problems as lack of resources and administrative support.</p

Financing of U.S. Biomedical Research and New Drug Approvals across Therapeutic Areas

We estimated U.S. biomedical research funding across therapeutic areas, determined the association with disease burden, and evaluated new drug approvals that resulted from this investment.We calculated funding from 1995 to 2005 and totaled Food and Drug Administration approvals in eight therapeutic areas (cardiovascular, endocrine, gastrointestinal, genitourinary, HIV/AIDS, infectious disease excluding HIV, oncology, and respiratory) primarily using public data. We then calculated correlations between funding, published estimates of disease burden, and drug approvals. Financial support for biomedical research from 1995 to 2005 increased across all therapeutic areas between 43% and 369%. Industry was the principal funder of all areas except HIV/AIDS, infectious disease, and oncology, which were chiefly sponsored by the National Institutes of Health (NIH). Total (rho = 0.70; P = .03) and industry funding (rho = 0.69; P = .04) were correlated with projected disease burden in high income countries while NIH support (rho = 0.80; P = .01) was correlated with projected disease burden globally. From 1995 to 2005 the number of new approvals was flat or declined across therapeutic areas, and over an 8-year lag period, neither total nor industry funding was correlated with future approvals.Across therapeutic areas, biomedical research funding increased substantially, appears aligned with disease burden in high income countries, but is not linked to new drug approvals. The translational gap between funding and new therapies is affecting all of medicine, and remedies must include changes beyond additional financial investment

Cardiovascular magnetic resonance myocardial feature tracking detects quantitative wall motion during dobutamine stress

Contains fulltext : 96698.pdf (publisher's version ) (Open Access)BACKGROUND: Dobutamine stress cardiovascular magnetic resonance (DS-CMR) is an established tool to assess hibernating myocardium and ischemia. Analysis is typically based on visual assessment with considerable operator dependency. CMR myocardial feature tracking (CMR-FT) is a recently introduced technique for tissue voxel motion tracking on standard steady-state free precession (SSFP) images to derive circumferential and radial myocardial mechanics.We sought to determine the feasibility and reproducibility of CMR-FT for quantitative wall motion assessment during intermediate dose DS-CMR. METHODS: 10 healthy subjects were studied at 1.5 Tesla. Myocardial strain parameters were derived from SSFP cine images using dedicated CMR-FT software (Diogenes MRI prototype; Tomtec; Germany). Right ventricular (RV) and left ventricular (LV) longitudinal strain (EllRV and EllLV) and LV long-axis radial strain (ErrLAX) were derived from a 4-chamber view at rest. LV short-axis circumferential strain (EccSAX) and ErrSAX; LV ejection fraction (EF) and volumes were analyzed at rest and during dobutamine stress (10 and 20 mug . kg(1). min(1)). RESULTS: In all volunteers strain parameters could be derived from the SSFP images at rest and stress. EccSAX values showed significantly increased contraction with DSMR (rest: -24.1 +/- 6.7; 10 mug: -32.7 +/- 11.4; 20 mug: -39.2 +/- 15.2; p < 0.05). ErrSAX increased significantly with dobutamine (rest: 19.6 +/- 14.6; 10 mug: 31.8 +/- 20.9; 20 mug: 42.4 +/- 25.5; p < 0.05). In parallel with these changes; EF increased significantly with dobutamine (rest: 56.9 +/- 4.4%; 10 mug: 70.7 +/- 8.1; 20 mug: 76.8 +/- 4.6; p < 0.05). Observer variability was best for LV circumferential strain (EccSAX ) and worst for RV longitudinal strain (EllRV) as determined by 95% confidence intervals of the difference. CONCLUSIONS: CMR-FT reliably detects quantitative wall motion and strain derived from SSFP cine imaging that corresponds to inotropic stimulation. The current implementation may need improvement to reduce observer-induced variance. Within a given CMR lab; this novel technique holds promise of easy and fast quantification of wall mechanics and strain