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Objectives/Goals: Academic research centers struggle to recruit and retain a diverse, competent clinical and translational science (CTS) workforce. The clinical research professional career pathway is particularly underrecognized among undergraduates, despite offering multiple career opportunities. Methods/Study Population: To address these challenges, two undergraduate outreach programs were developed. First, an undergraduate certificate program in CTS (UC-CTS) was designed to equip students with the skills and knowledge needed to enter the workforce immediately after graduation. Second, a “CTS Roadshow” was launched to build awareness of CTS careers within a variety of undergraduate programs and majors. In this recruitment initiative, principal investigators (PIs) and CRPs visit classrooms to share information about CTS career pathways and offer insights into the roles, responsibilities, and professional opportunities available in the field. Results/Anticipated Results: The UC-CTS program launched in Fall 2024 as a 12-credit certificate that includes two paid internships: one in patient care and one in research. Currently, the program has 5 students enrolled with an anticipated increase in enrollment to 20 students by Spring 2025. Similarly, the CTS Roadshow has reached an increasing number of students each year. Since its inception in Spring 2023, the CTS Roadshow has introduced over 750 undergraduates across 21 courses to CTS careers. The CTS Roadshow has engaged students from a variety of majors, including biology, psychology, medical sciences, legal, finance, accounting, and pre-health programs, increasing awareness of and interest in CTS careers. Discussion/Significance of Impact: Both programs aim to expose students to CTS careers early in their education, better preparing them for full-time CTS roles after graduation. A rise in qualified applicants pursuing CTS careers locally and regionally is expected, improving job satisfaction and retention through enhanced preparation for the career field.
Duchenne muscular dystrophy is a devastating neuromuscular disorder characterized by the loss of dystrophin, inevitably leading to cardiomyopathy. Despite publications on prophylaxis and treatment with cardiac medications to mitigate cardiomyopathy progression, gaps remain in the specifics of medication initiation and optimization.
Method:
This document is an expert opinion statement, addressing a critical gap in cardiac care for Duchenne muscular dystrophy. It provides thorough recommendations for the initiation and titration of cardiac medications based on disease progression and patient response. Recommendations are derived from the expertise of the Advance Cardiac Therapies Improving Outcomes Network and are informed by established guidelines from the American Heart Association, American College of Cardiology, and Duchenne Muscular Dystrophy Care Considerations. These expert-derived recommendations aim to navigate the complexities of Duchenne muscular dystrophy-related cardiac care.
Results:
Comprehensive recommendations for initiation, titration, and optimization of critical cardiac medications are provided to address Duchenne muscular dystrophy-associated cardiomyopathy.
Discussion:
The management of Duchenne muscular dystrophy requires a multidisciplinary approach. However, the diversity of healthcare providers involved in Duchenne muscular dystrophy can result in variations in cardiac care, complicating treatment standardization and patient outcomes. The aim of this report is to provide a roadmap for managing Duchenne muscular dystrophy-associated cardiomyopathy, by elucidating timing and dosage nuances crucial for optimal therapeutic efficacy, ultimately improving cardiac outcomes, and improving the quality of life for individuals with Duchenne muscular dystrophy.
Conclusion:
This document seeks to establish a standardized framework for cardiac care in Duchenne muscular dystrophy, aiming to improve cardiac prognosis.
There is a growing trend for studies run by academic and nonprofit organizations to have regulatory submission requirements. As a result, there is greater reliance on REDCap, an electronic data capture (EDC) widely used by researchers in these organizations. This paper discusses the development and implementation of the Rapid Validation Process (RVP) developed by the REDCap Consortium, aimed at enhancing regulatory compliance and operational efficiency in response to the dynamic demands of modern clinical research. The RVP introduces a structured validation approach that categorizes REDCap functionalities, develops targeted validation tests, and applies structured and standardized testing syntax. This approach ensures that REDCap can meet regulatory standards while maintaining flexibility to adapt to new challenges. Results from the application of the RVP on recent successive REDCap software version releases illustrate significant improvements in testing efficiency and process optimization, demonstrating the project’s success in setting new benchmarks for EDC system validation. The project’s community-driven responsibility model fosters collaboration and knowledge sharing and enhances the overall resilience and adaptability of REDCap. As REDCap continues to evolve based on feedback from clinical trialists, the RVP ensures that REDCap remains a reliable and compliant tool, ready to meet regulatory and future operational challenges.
Environment has long been known to have an impact on the evolution of galaxies, but disentangling its impact from mass evolution requires the careful analysis of statistically significant samples. By implementing cutting-edge visualisation methods to test and validate group-finding algorithms, we utilise a mass-complete sample of galaxies to $z \lt 0.1$ comprised of spectroscopic redshifts from prominent surveys such as the 2-degree Field Galaxy Redshift Survey and the Galaxy and Mass Assembly Survey. Utilising our group finding methods, we find 1 413 galaxy groups made up of 8 990 galaxies corresponding to 36% of galaxies associated with group environments. We also search for close pairs, with separations of $r_\mathrm{sep} \lt 50$$\text{h}^{-1}\text{kpc}$ and $v_\mathrm{sep} \lt 500 \: \text{km s}^{-1}$ within our sample and further classified them into major ($M_{sec}/M_{prim} \leq$ 0.25) and minor ($M_{sec}/M_{prim} \gt $ 0.25) pairs. To examine the impact of environmental factors, we employ bespoke WISE photometry, which facilitates accurate measurements of stellar mass and star formation rates and hence the best possible description of the variation of galaxy properties as a function of the local environment. Our analysis, employing a derived star-forming main sequence relation, reveals that star-formation (SF) within galaxies are pre-processed as a function of group membership. This is evident from the evolution of the star-forming and quenched population of galaxies. We see an increase in the fraction of quiescent galaxies relative to the field as group membership increases, and this excess of quenched galaxies relative to the field is later quantified through the use of the environmental quenching efficiency ($\varepsilon_{env}$) metric. Within the star-forming population, we observe SF pre-processing with the relative difference in specific star formation rates ($\Delta sSFR$), where we see a net decrease in SF as group membership increases, particularly at larger stellar masses. We again quantify this change within the SF population with our star formation deficiency ($\varepsilon_{SFD}$) metric. Our sample of close pairs at low stellar masses exhibit enhanced star formation efficiencies compared to the field, and at larger stellar mass ranges show large deficiencies. Separating the close pairs into major/minors and primary/secondaries reveals SF enhancements projected separation decreases within the minor pairs, this effect is even more pronounced within minor primaries. This research emphasises the importance of carefully studying the properties of galaxies within group environments to better understand the pre-processing of SF within galaxies. Our results show that the small-scale environments of galaxies influence star-forming properties even when stellar masses are kept constant. This demonstrates that galaxies do not evolve in isolation over cosmic time but are shaped by a complex interaction between their internal dynamics and external influences.
This article used text mining processes to map continuity and change in policy principles of the National Disability Insurance Scheme (NDIS) in Australia and reflect on the underlying agendas of reform. Specifically, this research aimed to: (1) examine the substantive content of the NDIS legislative, operational and reform documentation, (2) assess changes in objects, principles and issues over time, and (3) discuss the implications of these shifting logics and agendas. To achieve this, text mining approaches were applied to ten key NDIS documents from 2011 to 2019.
The findings included a low prevalence of ‘rights’-based terminology, sustained attention to Scheme ‘costs’ but limited latterly attention to ‘sustainability’, and increasing prominence of interpersonal (e.g., ‘family’, ‘community’) and decision-making terminology (e.g., ‘decision’, ‘review’). How these shifts have influenced subsequent proposed reforms is explored and ongoing dilemmas about designing policy that ensures rights and entitlements, while balancing cost, sustainability and consistency are identified.
This paper describes the implementation of curricula for Liberia's first-ever psychiatry training programme in 2019 and the actions of the only two Liberian psychiatrists in the country at the time in developing and executing a first-year postgraduate psychiatry training programme (i.e. residency) with support from international collaborators. It explores cultural differences in training models among collaborators and strategies to synergise them best. It highlights the assessment of trainees’ (residents’) basic knowledge on entry into the programme and how it guided immediate and short-term priority teaching objectives, including integrated training in neuroscience and neurology. The paper describes the strengths and challenges of this approach as well as opportunities for continued growth.
Improving the quality and conduct of multi-center clinical trials is essential to the generation of generalizable knowledge about the safety and efficacy of healthcare treatments. Despite significant effort and expense, many clinical trials are unsuccessful. The National Center for Advancing Translational Science launched the Trial Innovation Network to address critical roadblocks in multi-center trials by leveraging existing infrastructure and developing operational innovations. We provide an overview of the roadblocks that led to opportunities for operational innovation, our work to develop, define, and map innovations across the network, and how we implemented and disseminated mature innovations.
An academic hospital implemented a severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antigen-test–based strategy to facilitate discontinuation of precautions for patients admitted with a positive SARS-CoV-2 test. Of 171 patients that underwent antigen testing, 68% had an initial negative test performed a median of 5 days after admission. Antigen testing reduced isolation time by 144 hours.
Psilocybin Therapy (PT) is being increasingly studied as a psychiatric intervention. Personality relates to mental health and can be used to probe the nature of PT's therapeutic action.
Methods
In a phase 2, double-blind, randomized, active comparator controlled trial involving patients with moderate-to-severe major depressive disorder, we compared psilocybin with escitalopram, over a core 6-week trial period. Five-Factor model personality domains, Big Five Aspect Scale Openness aspects, Absorption, and Impulsivity were measured at Baseline, Week 6, and Month 6 follow-up.
Results
PT was associated with decreases in neuroticism (B = −0.63), introversion (B = −0.38), disagreeableness (B = −0.47), impulsivity (B = −0.40), and increases in absorption (B = 0.32), conscientiousness (B = 0.30), and openness (B = 0.23) at week 6, with neuroticism (B = −0.47) and disagreeableness (B = −0.41) remaining decreased at month 6. Escitalopram Treatment (ET) was associated with decreases in neuroticism (B = −0.38), disagreeableness (B = −0.26), impulsivity (B = −0.35), and increases in openness (B = 0.28) at week 6, with neuroticism (B = −0.46) remaining decreased at month 6. No significant between-condition differences were observed.
Conclusions
Personality changes across both conditions were in a direction consistent with improved mental health. With the possible exception of trait absorption, there were no compelling between-condition differences warranting conclusions regarding a selective action of PT (v. ET) on personality; however, post-ET changes in personality were significantly moderated by pre-trial positive expectancy for escitalopram, whereas expectancy did not moderate response to PT.
The 2022 update of the Canadian Stroke Best Practice Recommendations (CSBPR) for Acute Stroke Management, 7th edition, is a comprehensive summary of current evidence-based recommendations, appropriate for use by an interdisciplinary team of healthcare providers and system planners caring for persons with an acute stroke or transient ischemic attack. These recommendations are a timely opportunity to reassess current processes to ensure efficient access to acute stroke diagnostics, treatments, and management strategies, proven to reduce mortality and morbidity. The topics covered include prehospital care, emergency department care, intravenous thrombolysis and endovascular thrombectomy (EVT), prevention and management of inhospital complications, vascular risk factor reduction, early rehabilitation, and end-of-life care. These recommendations pertain primarily to an acute ischemic vascular event. Notable changes in the 7th edition include recommendations pertaining the use of tenecteplase, thrombolysis as a bridging therapy prior to mechanical thrombectomy, dual antiplatelet therapy for stroke prevention,1 the management of symptomatic intracerebral hemorrhage following thrombolysis, acute stroke imaging, care of patients undergoing EVT, medical assistance in dying, and virtual stroke care. An explicit effort was made to address sex and gender differences wherever possible. The theme of the 7th edition of the CSBPR is building connections to optimize individual outcomes, recognizing that many people who present with acute stroke often also have multiple comorbid conditions, are medically more complex, and require a coordinated interdisciplinary approach for optimal recovery. Additional materials to support timely implementation and quality monitoring of these recommendations are available at www.strokebestpractices.ca.
Whole-genome sequencing (WGS) shotgun metagenomics (metagenomics) attempts to sequence the entire genetic content straight from the sample. Diagnostic advantages lie in the ability to detect unsuspected, uncultivatable, or very slow-growing organisms.
Objective:
To evaluate the clinical and economic effects of using WGS and metagenomics for outbreak management in a large metropolitan hospital.
Design:
Cost-effectiveness study.
Setting:
Intensive care unit and burn unit of large metropolitan hospital.
Patients:
Simulated intensive care unit and burn unit patients.
Methods:
We built a complex simulation model to estimate pathogen transmission, associated hospital costs, and quality-adjusted life years (QALYs) during a 32-month outbreak of carbapenem-resistant Acinetobacter baumannii (CRAB). Model parameters were determined using microbiology surveillance data, genome sequencing results, hospital admission databases, and local clinical knowledge. The model was calibrated to the actual pathogen spread within the intensive care unit and burn unit (scenario 1) and compared with early use of WGS (scenario 2) and early use of WGS and metagenomics (scenario 3) to determine their respective cost-effectiveness. Sensitivity analyses were performed to address model uncertainty.
Results:
On average compared with scenario 1, scenario 2 resulted in 14 fewer patients with CRAB, 59 additional QALYs, and $75,099 cost savings. Scenario 3, compared with scenario 1, resulted in 18 fewer patients with CRAB, 74 additional QALYs, and $93,822 in hospital cost savings. The likelihoods that scenario 2 and scenario 3 were cost-effective were 57% and 60%, respectively.
Conclusions:
The use of WGS and metagenomics in infection control processes were predicted to produce favorable economic and clinical outcomes.
This study sought to identify coronavirus disease 2019 (COVID-19) risk communication materials distributed in Jamaica to mitigate the effects of the disease outbreak. It also sought to explore the effects of health risk communication on vulnerable groups in the context of the pandemic.
Methods:
A qualitative study was conducted, including a content analysis of health risk communications and in-depth interviews with 35 purposively selected elderly, physically disabled, persons with mental health disorders, representatives of government agencies, advocacy and service groups, and caregivers of the vulnerable. Axial coding was applied to data from the interviews, and all data were analyzed using the constant comparison technique.
Results:
Twelve of the 141 COVID-19 risk communication messages directly targeted the vulnerable. All participants were aware of the relevant risk communication and largely complied. Barriers to messaging awareness and compliance included inappropriate message medium for the deaf and blind, rural location, lack of Internet service or digital devices, limited technology skills, and limited connection to agencies that serve the vulnerable.
Conclusion:
The vulnerable are at increased risk in times of crisis. Accessibility of targeted information was inadequate for universal access to health information and support for vulnerable persons regardless of location and vulnerability.
Systemic venous hypertension and low cardiac output are believed to be important mediators of liver injury after the Fontan procedure. Pulmonary vasodilators have the potential to improve such haemodynamics. The aim of this study was to assess the acute effects of exercise on liver stiffness and venous pressures and to assess the impact of inhaled Treprostinil on this response.
Methods:
In this prospective, double-blind, placebo-controlled, crossover trial, 14 patients with a Fontan circulation were randomised to inhalation of placebo and Treprostinil. Incremental and constant work rate exercise tests were performed to assess the effect of Treprostinil on exercise tolerance. Venous pressures were measured throughout and liver stiffness at rest and immediately after peak exercise.
Results:
Mean age was 27.8 ± 7.9 years and 66% were females. Exercise acutely increased liver stiffness by 30% (mean shear wave speed: 2.38 ± 0.71 versus 2.89 ± 0.51 ms, p = 0.02). Peripheral venous pressures increased acutely during both incremental (12.1 ± 2.4 versus 22.6 ± 8.0 mmHg, p < 0.001) and constant work rate exercise (12.5 ± 2.5 versus 23.4 ± 5.2 mmHg, p < 0.001). Overall, Treprostinil failed to attenuate exercise-induced increases in liver stiffness. Compared with placebo, Treprostinil did not significantly impact venous pressure responses, VO2peak, nor exercise endurance times.
Conclusions:
Peripheral venous pressure increased acutely during exercise by an average of 88% above baseline and was not altered by administration of inhaled Treprostinil. Liver stiffness measured immediately post-exercise increased acutely by an average of 30%, with no attenuation following Treprostinil inhalation.
OBJECTIVES/GOALS: Innovations with positive health impact are a high priority for NCATS and CTSAs. Program design that uses the Causal Pathway approach incorporates performance indicators that assess impact. We applied Causal Pathway thinking to an ongoing national program to enhance the evaluation of program impact. We report Lessons Learned. METHODS/STUDY POPULATION: We conducted a day-long onsite workshop to introduce the model to the project team, build capacity, and map the existing program elements to Logic Models representing program Specific Aims. A local Causal Pathway (CP) champion was identified. Alignment of the Logic Models with the CP approach (input→activities→ outputs→effects/impact) developed iteratively through biweekly, then monthly conferral among stakeholders. Key tasks included distinguishing among activities, outputs, and effects (impacts), and identification of performance indicators for each stage of the Causal Pathway. Visualization tools and an additional late stage half-day workshop were used to foster consensus. Implementation of the CP model tested the feasibility of collecting specific indicators and prompted model revisions. RESULTS/ANTICIPATED RESULTS: Program leadership and team members (n = 30) participated in the kick-off workshop. Four Specific Aims were mapped to Logic Models. Multiple Causal Pathway (CP) diagrams, one for each project in the program, were developed and mapped to Aims. Alignment of CP threads to Aims and identification of performance indicators required iteration. CP threads converged onto common final Impacts, sometimes crossing to another Aim. Performance indicators for operations were readily accessible to team members, and less so for impacts. Assumptions about program effects were subjected to specific indicators. Over time, Leadership noticed more expression of CP thinking in daily activities. New projects developed during this period incorporated the CP approach. Teams were able to streamline and simplify Logic/CP models. DISCUSSION/SIGNIFICANCE OF IMPACT: Through capacity-building and mentored exercises, an innovation team was able to infuse CP thinking into the evaluation of their ongoing program. The CP approach to design and evaluation maps progress and indicators across the life of a program from initial activities to its ultimate impact.
Previous literature supports exercise as a preventative agent for prenatal depression; however, treatment effects for women at risk for prenatal depression remain unexplored. The purpose of the study was to examine whether exercise can lower depressive symptoms among women who began pregnancy at risk for depression using both a statistical significance and reliable and clinically significant change criteria.
Methods
This study is a secondary analysis of two randomized controlled trials that followed the same exercise protocol. Pregnant women were allocated to an exercise intervention group (IG) or control group (CG). All participants completed the Center for Epidemiological Depression (CES-D) scale at gestational week 9–16 and 36–38. Women with a baseline score ⩾16 were included. A clinically reliable cut-off was calculated as a 7-point change in scores from pre- to post-intervention.
Results
Thirty-six women in the IG and 25 women in the CG scored ⩾16 on the CES-D at baseline. At week 36–38 the IG had a statistically significant lower CES-D score (14.4 ± 8.6) than the CG (19.4 ± 11.1; p < 0.05). Twenty-two women in the IG (61%) had a clinically reliable decrease in their post-intervention score compared to eight women in the CG (32%; p < 0.05). Among the women who met the reliable change criteria, 18 (81%) in the IG and 7 (88%) in the CG had a score <16 post-intervention, with no difference between groups (p > 0.05).
Conclusions
A structured exercise program might be a useful treatment option for women at risk for prenatal depression.
OBJECTIVES/SPECIFIC AIMS: Upper-extremity (UE) impairment affects 88% of stroke survivors due to dysfunctional shoulder-hand coordination. Patients may be able to grasp with the arm at rest, but unable to grasp in a functional context (eg, from a high shelf) because shoulder use elicits involuntary hand muscle activity. Further, much rehabilitation research is directed at unsuccessful stroke recovery (patients with persistent UE impairment) but very little towards patients who show successful clinical recovery (such as those with mild UE impairment) even though these patients have attained the desired rehabilitation outcome. We examined the neurophysiological trajectory of successful compared to unsuccessful post-stroke recovery in the context of functional UE movements to clearly identify what factors are necessary for successful recovery of functional UE movements after stroke. METHODS/STUDY POPULATION: We studied 3 populations: (1) mildly-impaired patients, early (at <17 d, 30 d, 90 d, and 180 d) after stroke as a model of successful post-stroke recovery, (2) moderately-impaired, chronic patients (>6-months post stroke) with persistent hand function impairment, as a model of incomplete post-stroke recovery (unsuccessful recovery), and (3) Healthy age-range matched controls. We used transcranial magnetic stimulation (TMS) in all 3 groups at the given time points to measure corticomotor excitability (motor evoked potentials, recruitment curve), corticomotor inhibition (short-interval intracortical inhibition, long-interval intracortical inhibition), and intracortical facilitation of hand muscles with the shoulder positioned in different degrees of flexion or abduction (these shoulder positions are known to elicit involuntary, undesired hand muscle activation, which leads to UE dysfunction and impairment in individuals with stroke). RESULTS/ANTICIPATED RESULTS: Data collection are in process and will be presented. Preliminary data from controls shows that corticomotor excitability of selected hand muscles is affected by changes in shoulder position. Preliminary findings in controls are consistent with clinical findings in stroke that certain shoulder positions elicit involuntary and undesired hand muscle activation, leading to UE dysfunction and disability. Findings from the stroke groups will be presented. DISCUSSION/SIGNIFICANCE OF IMPACT: We hypothesize that this centrally-facilitated coupling between shoulder and hand muscles is disrupted after stroke, which may play a central role in the inability of patients to perform functional UE movements. By comparing the TMS metrics in mildly-impaired Versus moderately-impaired chronic patients, we will be able to identify the longitudinal change in neurophysiology underlying shoulder-hand coordination that is associated with successful or unsuccessful clinical recovery of UE function after stroke. Thus, these findings will help us distinguish between the neurophysiology underlying successful from unsuccessful UE recovery leading to more mechanism-based interventions for UE dysfunction post stroke in the future.
To investigate the potential dietary impact of the opening of new retailers of healthy foods.
Design
Systematic review of the peer-reviewed research literature.
Setting
References published before November 2015 were retrieved from MEDLINE, EMBASE and Web of Science databases using keyword searches.
Subjects
The outcome of the review was change in fruit and vegetable consumption among adults.
Results
Of 3514 references retrieved, ninety-two articles were reviewed in full text, and twenty-three articles representing fifteen studies were included. Studies used post-test only (n 4), repeated cross-sectional (n 4) and repeated measures designs (n 7) to evaluate the dietary impact of supermarket (n 7), farmers’ market (n 4), produce stand (n 2) or mobile market (n 2) openings. Evidence of increased fruit and vegetable consumption was most consistent among adults who began shopping at the new retailer. Three of four repeated measures studies found modest, albeit not always statistically significant, increases in fruit and vegetable consumption (range 0·23–0·54 servings/d) at 6–12 months after baseline. Dietary change among residents of the broader community where the new retailer opened was less consistent.
Conclusions
The methodological quality of studies, including research designs, sampling methods, follow-up intervals and outcome measures, ranged widely. Future research should align methodologically with previous work to facilitate meta-analytic synthesis of results. Opening a new retailer may result in modest short-term increases in fruit and vegetable consumption among adults who choose to shop there, but the potential longer-term dietary impact on customers and its impact on the broader community remain unclear.
Training for the clinical research workforce does not sufficiently prepare workers for today’s scientific complexity; deficiencies may be ameliorated with training. The Enhancing Clinical Research Professionals’ Training and Qualifications developed competency standards for principal investigators and clinical research coordinators.
Methods
Clinical and Translational Science Awards representatives refined competency statements. Working groups developed assessments, identified training, and highlighted gaps.
Results
Forty-eight competency statements in 8 domains were developed.
Conclusions
Training is primarily investigator focused with few programs for clinical research coordinators. Lack of training is felt in new technologies and data management. There are no standardized assessments of competence.
The translation of discoveries to drugs, devices, and behavioral interventions requires well-prepared study teams. Execution of clinical trials remains suboptimal due to varied quality in design, execution, analysis, and reporting. A critical impediment is inconsistent, or even absent, competency-based training for clinical trial personnel.
Methods
In 2014, the National Center for Advancing Translational Science (NCATS) funded the project, Enhancing Clinical Research Professionals’ Training and Qualifications (ECRPTQ), aimed at addressing this deficit. The goal was to ensure all personnel are competent to execute clinical trials. A phased structure was utilized.
Results
This paper focuses on training recommendations in Good Clinical Practice (GCP). Leveraging input from all Clinical and Translational Science Award hubs, the following was recommended to NCATS: all investigators and study coordinators executing a clinical trial should understand GCP principles and undergo training every 3 years, with the training method meeting the minimum criteria identified by the International Conference on Harmonisation GCP.
Conclusions
We anticipate that industry sponsors will acknowledge such training, eliminating redundant training requests. We proposed metrics to be tracked that required further study. A separate task force was composed to define recommendations for metrics to be reported to NCATS.