Browsing by Subject "Workflow"
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Item Open Access Creating and parameterizing patient-specific deep brain stimulation pathway-activation models using the hyperdirect pathway as an example.(PloS one, 2017-01) Gunalan, Kabilar; Chaturvedi, Ashutosh; Howell, Bryan; Duchin, Yuval; Lempka, Scott F; Patriat, Remi; Sapiro, Guillermo; Harel, Noam; McIntyre, Cameron CBackground
Deep brain stimulation (DBS) is an established clinical therapy and computational models have played an important role in advancing the technology. Patient-specific DBS models are now common tools in both academic and industrial research, as well as clinical software systems. However, the exact methodology for creating patient-specific DBS models can vary substantially and important technical details are often missing from published reports.Objective
Provide a detailed description of the assembly workflow and parameterization of a patient-specific DBS pathway-activation model (PAM) and predict the response of the hyperdirect pathway to clinical stimulation.Methods
Integration of multiple software tools (e.g. COMSOL, MATLAB, FSL, NEURON, Python) enables the creation and visualization of a DBS PAM. An example DBS PAM was developed using 7T magnetic resonance imaging data from a single unilaterally implanted patient with Parkinson's disease (PD). This detailed description implements our best computational practices and most elaborate parameterization steps, as defined from over a decade of technical evolution.Results
Pathway recruitment curves and strength-duration relationships highlight the non-linear response of axons to changes in the DBS parameter settings.Conclusion
Parameterization of patient-specific DBS models can be highly detailed and constrained, thereby providing confidence in the simulation predictions, but at the expense of time demanding technical implementation steps. DBS PAMs represent new tools for investigating possible correlations between brain pathway activation patterns and clinical symptom modulation.Item Open Access Development and implementation of a proficiency testing program for Luminex bead-based cytokine assays.(Journal of Immunological Methods, 2014-07) Lynch, Heather E; Sanchez, Ana M; D'Souza, M Patricia; Rountree, Wes; Denny, Thomas N; Kalos, Michael; Sempowski, Gregory DLuminex bead array assays are widely used for rapid biomarker quantification due to the ability to measure up to 100 unique analytes in a single well of a 96-well plate. There has been, however, no comprehensive analysis of variables impacting assay performance, nor development of a standardized proficiency testing program for laboratories performing these assays. To meet this need, the NIH/NIAID and the Cancer Immunotherapy Consortium of the Cancer Research Institute collaborated to develop and implement a Luminex assay proficiency testing program as part of the NIH/NIAID-sponsored External Quality Assurance Program Oversight Laboratory (EQAPOL) at Duke University. The program currently monitors 25 domestic and international sites with two external proficiency panels per year. Each panel includes a de-identified commercial Luminex assay kit with standards to quantify human IFNγ, TNFα, IL-6, IL-10 and IL-2, and a series of recombinant cytokine-spiked human serum samples. All aspects of panel development, testing and shipping are performed under GCLP by EQAPOL support teams. Following development testing, a comprehensive site proficiency scoring system comprised of timeliness, protocol adherence, accuracy and precision was implemented. The overall mean proficiency score across three rounds of testing has remained stable (EP3: 76%, EP4: 75%, EP5: 77%); however, a more detailed analysis of site reported results indicates a significant improvement of intra- (within) and inter- (between) site variation, suggesting that training and remediation for poor performing sites may be having a positive impact on proficiency. Through continued proficiency testing, identification of variables affecting Luminex assay outcomes will strengthen efforts to bring standardization to the field.Item Open Access Development and initial testing of the stroke rapid-treatment readiness tool.(J Neurosci Nurs, 2014-10) Olson, DaiWai M; Cox, Margueritte; Constable, Mark; Britz, Gavin W; Lin, Cheryl B; Zimmer, Louise O; Fonarow, Gregg C; Schwamm, Lee H; Peterson, Eric DNo instruments are currently available to help health systems identify target areas for reducing door-to-needle times for the administration of intravenous tissue plasminogen activator to eligible patients with ischemic stroke. A 67-item Likert-scale survey was administered by telephone to stroke personnel at 252 U.S. hospitals participating in the "Get With The Guidelines-Stroke" quality improvement program. Factor analysis was used to refine the instrument to a four-factor 29-item instrument that can be used by hospitals to assess their readiness to administer intravenous tissue plasminogen activator within 60 minutes of patient hospital arrival.Item Open Access Effective Implementation of Enhanced Recovery Pathway Programs: The Key to Disseminating Evidence into Practice.(Jt Comm J Qual Patient Saf, 2015-10) Hopkins, Thomas J; Miller, Timothy EItem Open Access FlowKit: A Python Toolkit for Integrated Manual and Automated Cytometry Analysis Workflows.(Frontiers in immunology, 2021-01) White, Scott; Quinn, John; Enzor, Jennifer; Staats, Janet; Mosier, Sarah M; Almarode, James; Denny, Thomas N; Weinhold, Kent J; Ferrari, Guido; Chan, CliburnAn important challenge for primary or secondary analysis of cytometry data is how to facilitate productive collaboration between domain and quantitative experts. Domain experts in cytometry laboratories and core facilities increasingly recognize the need for automated workflows in the face of increasing data complexity, but by and large, still conduct all analysis using traditional applications, predominantly FlowJo. To a large extent, this cuts domain experts off from the rapidly growing library of Single Cell Data Science algorithms available, curtailing the potential contributions of these experts to the validation and interpretation of results. To address this challenge, we developed FlowKit, a Gating-ML 2.0-compliant Python package that can read and write FCS files and FlowJo workspaces. We present examples of the use of FlowKit for constructing reporting and analysis workflows, including round-tripping results to and from FlowJo for joint analysis by both domain and quantitative experts.Item Open Access Implementing a Continuous Quality Improvement Program in a High-Volume Clinical Echocardiography Laboratory: Improving Care for Patients With Aortic Stenosis.(Circ Cardiovasc Imaging, 2016-03) Samad, Zainab; Minter, Stephanie; Armour, Alicia; Tinnemore, Amanda; Sivak, Joseph A; Sedberry, Brenda; Strub, Karen; Horan, Seanna M; Harrison, J Kevin; Kisslo, Joseph; Douglas, Pamela S; Velazquez, Eric JBACKGROUND: The management of aortic stenosis rests on accurate echocardiographic diagnosis. Hence, it was chosen as a test case to examine the utility of continuous quality improvement (CQI) approaches to increase echocardiographic data accuracy and reliability. A novel, multistep CQI program was designed and prospectively used to investigate whether it could minimize the difference in aortic valve mean gradients reported by echocardiography when compared with cardiac catheterization. METHODS AND RESULTS: The Duke Echo Laboratory compiled a multidisciplinary CQI team including 4 senior sonographers and MD faculty to develop a mapped CQI process that incorporated Intersocietal Accreditation Commission standards. Quarterly, the CQI team reviewed all moderate- or greater-severity aortic stenosis echocardiography studies with concomitant catheterization data, and deidentified individual and group results were shared at meetings attended by cardiologists and sonographers. After review of 2011 data, the CQI team proposed specific amendments implemented over 2012: the use of nontraditional imaging and Doppler windows as well as evaluation of aortic gradients by a second sonographer. The primary outcome measure was agreement between catheterization- and echocardiography-derived mean gradients calculated by using the coverage probability index with a prespecified acceptable echocardiography-catheterization difference of <10 mm Hg in mean gradient. Between January 2011 and January 2014, 2093 echocardiograms reported moderate or greater aortic stenosis. Among cases with available catheterization data pre- and post-CQI, the coverage probability index increased from 54% to 70% (P=0.03; 98 cases, year 2011; 70 cases, year 2013). The proportion of patients referred for invasive valve hemodynamics decreased from 47% pre-CQI to 19% post-CQI (P<0.001). CONCLUSIONS: A laboratory practice pattern that was amenable to reform was identified, and a multistep modification was designed and implemented that produced clinically valuable performance improvements. The new protocol improved aortic stenosis mean gradient agreement between echocardiography and catheterization and was associated with a measurable decrease in referrals of patients for invasive studies.Item Open Access Leukopak PBMC sample processing for preparing quality control material to support proficiency testing programs.(Journal of Immunological Methods, 2014-07) Garcia, Ambrosia; Keinonen, Sarah; Sanchez, Ana M; Ferrari, Guido; Denny, Thomas N; Moody, M AnthonyExternal proficiency testing programs designed to evaluate the performance of end-point laboratories involved in vaccine and therapeutic clinical trials form an important part of clinical trial quality assurance. Good clinical laboratory practice (GCLP) guidelines recommend both assay validation and proficiency testing for assays being used in clinical trials, and such testing is facilitated by the availability of large numbers of well-characterized test samples. These samples can be distributed to laboratories participating in these programs and allow monitoring of laboratory performance over time and among participating sites when results are obtained with samples derived from a large master set. The leukapheresis procedure provides an ideal way to collect samples from participants that can meet the required number of cells to support these activities. The collection and processing of leukapheresis samples require tight coordination between the clinical and laboratory teams to collect, process, and cryopreserve large number of samples within the established ideal time of ≤8 hours. Here, we describe our experience with a leukapheresis cryopreseration program that has been able to preserve the functionality of cellular subsets and that provides the sample numbers necessary to run an external proficiency testing program.Item Open Access Standardizing clinical trials workflow representation in UML for international site comparison.(PLoS One, 2010-11-09) de Carvalho, Elias Cesar Araujo; Jayanti, Madhav Kishore; Batilana, Adelia Portero; Kozan, Andreia MO; Rodrigues, Maria J; Shah, Jatin; Loures, Marco R; Patil, Sunita; Payne, Philip; Pietrobon, RicardoBACKGROUND: With the globalization of clinical trials, a growing emphasis has been placed on the standardization of the workflow in order to ensure the reproducibility and reliability of the overall trial. Despite the importance of workflow evaluation, to our knowledge no previous studies have attempted to adapt existing modeling languages to standardize the representation of clinical trials. Unified Modeling Language (UML) is a computational language that can be used to model operational workflow, and a UML profile can be developed to standardize UML models within a given domain. This paper's objective is to develop a UML profile to extend the UML Activity Diagram schema into the clinical trials domain, defining a standard representation for clinical trial workflow diagrams in UML. METHODS: Two Brazilian clinical trial sites in rheumatology and oncology were examined to model their workflow and collect time-motion data. UML modeling was conducted in Eclipse, and a UML profile was developed to incorporate information used in discrete event simulation software. RESULTS: Ethnographic observation revealed bottlenecks in workflow: these included tasks requiring full commitment of CRCs, transferring notes from paper to computers, deviations from standard operating procedures, and conflicts between different IT systems. Time-motion analysis revealed that nurses' activities took up the most time in the workflow and contained a high frequency of shorter duration activities. Administrative assistants performed more activities near the beginning and end of the workflow. Overall, clinical trial tasks had a greater frequency than clinic routines or other general activities. CONCLUSIONS: This paper describes a method for modeling clinical trial workflow in UML and standardizing these workflow diagrams through a UML profile. In the increasingly global environment of clinical trials, the standardization of workflow modeling is a necessary precursor to conducting a comparative analysis of international clinical trials workflows.Item Unknown The Center for HIV/AIDS Vaccine Immunology (CHAVI) multi-site quality assurance program for cryopreserved human peripheral blood mononuclear cells.(J Immunol Methods, 2014-07) Sarzotti-Kelsoe, Marcella; Needham, Leila K; Rountree, Wes; Bainbridge, John; Gray, Clive M; Fiscus, Susan A; Ferrari, Guido; Stevens, Wendy S; Stager, Susan L; Binz, Whitney; Louzao, Raul; Long, Kristy O; Mokgotho, Pauline; Moodley, Niranjini; Mackay, Melanie; Kerkau, Melissa; McMillion, Takesha; Kirchherr, Jennifer; Soderberg, Kelly A; Haynes, Barton F; Denny, Thomas NThe Center for HIV/AIDS Vaccine Immunology (CHAVI) consortium was established to determine the host and virus factors associated with HIV transmission, infection and containment of virus replication, with the goal of advancing the development of an HIV protective vaccine. Studies to meet this goal required the use of cryopreserved Peripheral Blood Mononuclear Cell (PBMC) specimens, and therefore it was imperative that a quality assurance (QA) oversight program be developed to monitor PBMC samples obtained from study participants at multiple international sites. Nine site-affiliated laboratories in Africa and the USA collected and processed PBMCs, and cryopreserved PBMC were shipped to CHAVI repositories in Africa and the USA for long-term storage. A three-stage program was designed, based on Good Clinical Laboratory Practices (GCLP), to monitor PBMC integrity at each step of this process. The first stage evaluated the integrity of fresh PBMCs for initial viability, overall yield, and processing time at the site-affiliated laboratories (Stage 1); for the second stage, the repositories determined post-thaw viability and cell recovery of cryopreserved PBMC, received from the site-affiliated laboratories (Stage 2); the third stage assessed the long-term specimen storage at each repository (Stage 3). Overall, the CHAVI PBMC QA oversight program results highlight the relative importance of each of these stages to the ultimate goal of preserving specimen integrity from peripheral blood collection to long-term repository storage.Item Unknown The Immunology Quality Assessment Proficiency Testing Program for CD3⁺4⁺ and CD3⁺8⁺ lymphocyte subsets: a ten year review via longitudinal mixed effects modeling.(Journal of Immunological Methods, 2014-07) Bainbridge, J; Wilkening, CL; Rountree, W; Louzao, R; Wong, J; Perza, N; Garcia, A; Denny, TNSince 1999, the National Institute of Allergy and Infectious Diseases Division of AIDS (NIAID DAIDS) has funded the Immunology Quality Assessment (IQA) Program with the goal of assessing proficiency in basic lymphocyte subset immunophenotyping for each North American laboratory supporting the NIAID DAIDS HIV clinical trial networks. Further, the purpose of this program is to facilitate an increase in the consistency of interlaboratory T-cell subset measurement (CD3(+)4(+)/CD3(+)8(+) percentages and absolute counts) and likewise, a decrease in intralaboratory variability. IQA T-cell subset measurement proficiency testing was performed over a ten-year period (January 2003-July 2012), and the results were analyzed via longitudinal analysis using mixed effects models. The goal of this analysis was to describe how a typical laboratory (a statistical modeling construct) participating in the IQA Program performed over time. Specifically, these models were utilized to examine trends in interlaboratory agreement, as well as successful passing of proficiency testing. Intralaboratory variability (i.e., precision) was determined by the repeated measures variance, while fixed and random effects were taken into account for changes in interlaboratory agreement (i.e., accuracy) over time. A flow cytometer (single-platform technology, SPT) or a flow cytometer/hematology analyzer (dual-platform technology, DPT) was also examined as a factor for accuracy and precision. The principal finding of this analysis was a significant (p<0.001) increase in accuracy of T-cell subset measurements over time, regardless of technology type (SPT or DPT). Greater precision was found in SPT measurements of all T-cell subset measurements (p<0.001), as well as greater accuracy of SPT on CD3(+)4(+)% and CD3(+)8(+)% assessments (p<0.05 and p<0.001, respectively). However, the interlaboratory random effects variance in DPT results indicates that for some cases DPT can have increased accuracy compared to SPT. Overall, these findings demonstrate that proficiency in and among IQA laboratories have, in general, improved over time and that platform type differences in performance do exist.