A Model for Developing, Evaluating, and Disseminating Best Practices in Education and Training: NC TraCS Education Development and Evaluation Model

With the shift towards team-based translational science came recognition that existing strategies for training individual investigators and retaining them in the biomedical workforce would be inadequate. To support this shift, it is important to: develop innovative strategies to educate and train diverse members of research teams; evaluate those programs; and disseminate best practices broadly. We have developed a four-phase model to facilitate the development, evaluation, and widespread dissemination of innovative strategies to train the biomedical research workforce. Phase I (Innovate) involves small scale trials of programs to address perceived training needs or new methods of delivery. Phase II (Incubate) refines and evaluates promising Phase I activities on a larger scale. Phase III (Translate) seeks to replicate initial successes either locally (Phase IIIa) or with other interested institutions (Phase IIIb). Phase IV (Disseminate) assesses whether identified local best practices can have success on a broader scale. We present specific examples from our own experience that demonstrate the utility of this model, and then conclude with opportunities and challenges related to the education and training of this workforce

Hepatic gene expression during treatment with peginterferon and ribavirin: Identifying molecular pathways for treatment response

The reasons for hepatitis C treatment failure remain unknown but may be related to different host responses to therapy. In this study, we compared hepatic gene expression in patients prior to and during peginterferon and ribavirin therapy. In the on-treatment group, patients received either ribavirin for 72 hours prior to peginterferon alpha-2a injection or peginterferon alpha-2a for 24 hours, prior to biopsy. The patients were grouped into rapid responders (RRs) with a greater than 2-log drop and slow responders (SRs) with a less than 2-log drop in hepatitis C virus RNA by week 4. Pretreatment biopsy specimens were obtained from a matched control group. The pretreatment patients were grouped as RRs or SRs on the basis of the subsequent treatment response. Gene expression profiling was performed with Affymetrix microarray technology. Known interferon-stimulated genes (ISGs) were induced in treated patients. In the pretreatment group, future SRs had higher pretreatment ISG expression than RRs. On treatment, RRs and SRs had similar absolute ISG expression, but when it was corrected for the baseline expression with the pretreatment group, RRs showed a greater fold change in ISGs, whereas SRs showed a greater change in interferon (IFN)-inhibitory pathways. The patients pretreated with ribavirin had heightened induction of IFN-related genes and down-regulation of genes involved in IFN inhibition and hepatic stellate cell activation

Clinical and Translational Scientist Career Success: Metrics for Evaluation

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

Is quinine a suitable probe to assess the hepatic drug-metabolizing enzyme CYP3A4?

AIMS: To evaluate the antimalarial agent quinine as a potential in vivo probe for hepatic cytochrome P450 (CYP) 3A4 activity. METHODS: Ten healthy adult volunteers received, by randomized crossover design, either a single oral dose of quinine sulphate (600 mg) alone, or quinine sulphate (600 mg) plus the CYP3A4 inhibitor troleandomycin (TAO; 500 mg every 8 h). Plasma and urine samples were collected before quinine administration, and up to 48 h thereafter, then analysed by h.p.l.c. for both quinine and its CYP3A4-generated metabolite, 3-hydroxyquinine. During both phases, the erythromycin breath test (ERMBT) was administered at specific times to assess hepatic CYP3A4 activity. RESULTS: Compared with control, TAO treatment significantly decreased the mean time-averaged ERMBT result by 77% (95% CI, 68, 85%), the mean apparent oral clearance of quinine (CL/F ) by 45% (95% CI, 39, 52%), and the mean apparent formation clearance of 3-hydroxyquinine (CL3-OH) by 81% (95% CI, 76, 87%). There was no correlation between the TAO-mediated percent decrease in the time-averaged ERMBT result and the percent decrease in CL/F or in CL3-OH. When TAO and control treatments were analysed separately, there were no significant correlations between the time-averaged ERMBT result and CL/F, CL3-OH, or single plasma quinine concentration at 12, 24, and 48 h. CONCLUSIONS: Quinine may be a useful probe to detect inhibition of liver CYP3A4 activity within an individual. Further studies are needed to determine whether it can provide a quantitative measure of CYP3A4 activity suitable for intersubject comparison

Catalyzing communities of research rigour champions.

The biomedical sciences must maintain and enhance a research culture that prioritizes rigour and transparency. The US National Institute of Neurological Disorders and Stroke convened a workshop entitled Catalyzing Communities of Research Rigor Champions that brought together a diverse group of leaders in promoting research rigour and transparency (identified as rigour champions) to discuss strategies, barriers and resources for catalyzing technical, cultural and educational changes in the biomedical sciences. This article summarizes 2 days of panels and discussions and provides an overview of critical barriers to research rigour, perspectives behind reform initiatives and considerations for stakeholders across science. Additionally, we describe applications of network science to foster, maintain and expand cultural changes related to scientific rigour and opportunities to embed rigourous practices into didactic courses, training experiences and degree programme requirements. We hope this piece provides a primer for the wider research community on current discussions and actions and inspires individuals to build, join or expand collaborative networks within their own institutions that prioritize rigourous research practices

Implementation and Evaluation of a National Well-Being Curriculum for KL2 Scholars

The study aimed to pilot test a well-being curriculum for KL2 scholars to be used across the Clinical and Translational Science Award consortium. Between November 2022, and May 2023, 36 KL2 scholars from 25 hubs participated in the program. The General Well-Being Index for U.S. Workers and the Patient Reported Outcomes Measurement Information System (PROMIS-29) were completed by scholars before and after the program. Postparticipation, there was a trend of improvement in the domains of well-being, sleep, anxiety, and fatigue. Implementing a virtual synchronous well-being curriculum allowed the scholars to connect across the consortium and improve their well-being

What is well-being? A scoping review of the conceptual and operational definitions of occupational well-being

Well-being is a multifaceted construct that is used across disciplines to portray a state of wellness, health, and happiness. While aspects of well-being seem universal, how it is depicted in the literature has substantial variation. The aim of this scoping review was to identify conceptual and operational definitions of well-being within the field of occupational health. Broad search terms were used related to well-being and scale/assessment. Inclusion criteria were (1) peer-reviewed articles, (2) published in English, (3) included a measure of well-being in the methods and results section of the article, and (4) empirical paper. The searches resulted in 4394 articles, 3733 articles were excluded by reading the abstract, 661 articles received a full review, and 273 articles were excluded after a full review, leaving 388 articles that met our inclusion criteria and were used to extract well-being assessment information. Many studies did not define well-being or link their conceptual definition to the operational assessment tool being used. There were 158 assessments of well-being represented across studies. Results highlight the lack of a consistent definitions of well-being and standardized measurements

Clinical and translational scientist career success: metrics for evaluation

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

Clinical and Translational Scientist Career Success: Metrics for Evaluation

A method is described to incorporate bilexical preferences between phrase heads, such as selection restrictions, in a Maximum-Entropy parser for Dutch. The bilexical preferences are modelled as association rates which are determined on the basis of a very large parsed corpus (about 500M words). We show that the incorporation of such selftrained preferences improves parsing accuracy significantly.