We are developing the novel αIIbβ3 antagonist, RUC-4, for subcutaneously (SC)-administered first-point-of-medical-contact treatment for ST segment elevation myocardial infarction (STEMI).

We studied the (1) pharmacokinetics (PK) of RUC-4 at 1.0, 1.93, and 3.86 mg/kg intravenous (IV), intramuscular (IM), and SC in non-human primates (NHPs); (2) impact of aspirin on RUC-4 IC50 in human platelet-rich plasma (PRP); (3) effect of different anticoagulants on the RUC-4 IC50 in human PRP; and (4) relationship between αIIbβ3 receptor blockade by RUC-4 and inhibition of ADP-induced platelet aggregation.

(1) All doses of RUC-4 were well tolerated, but animals demonstrated variable temporary bruising. IM and SC RUC-4 reached dose-dependent peak levels within 5–15 minutes, with T1/2 s between 0.28 and 0.56 hours. Platelet aggregation studies in NHPs receiving IM RUC-4 demonstrated >80% inhibition of the initial slope of ADP-induced aggregation with all three doses 30 minutes post-dosing, with subsequent dose-dependent loss of inhibition over 4–5 hours. (2) The RUC-4 IC50 for ADP-induced platelet aggregation was unaffected by aspirin treatment (40±9 nM vs 37±5 nM; p = 0.39). (3) The RUC-4 IC50 was significantly higher in PRP prepared from D-phenylalanyl-prolyl-arginyl chloromethyl ketone (PPACK)-anticoagulated blood compared to citrate-anticoagulated blood using either thrombin receptor activating peptide (TRAP) (122±17 vs 66±25 nM; p = 0.05; n = 4) or ADP (102±22 vs 54±13; p<0.001; n = 5). (4) There was a close correspondence between receptor blockade and inhibition of ADP-induced platelet aggregation, with aggregation inhibition beginning with ~40% receptor blockade and becoming nearly complete at >80% receptor blockade.

Based on these results and others, RUC-4 has now progressed to formal preclinical toxicology studies.

Although classical randomized clinical trials (RCTs) are the gold standard for proof of drug efficacy, randomized discontinuation trials (RDTs), sometimes called “enriched” trials, are used increasingly, especially in psychiatric maintenance studies.

A narrative review of two decades of experience with RDTs.

RDTs in psychiatric maintenance trials tend to use a dependent variable as a predictor: treatment response. Treatment responders are assessed for treatment response. This tautology in the logic of RDTs renders them invalid, since the predictor and the outcome are the same variable. Although RDTs can be designed to avoid this tautologous state of affairs, like using independent predictors of outcomes, such is not the case with psychiatric maintenance studies

Further, purported benefits of RDTs regarding feasibility were found to be questionable. Specifically, RDTs do not enhance statistical power in many settings, and, because of high dropout rates, produce results of questionable validity. Any claimed benefits come with notably reduced generalizability.

RDTs appear to be scientifically invalid as used in psychiatric maintenance designs. Their purported feasibility benefits are not seen in actual trials for psychotropic drugs. There is warrant for changes in federal policy regarding marketing indications for maintenance efficacy using the RDT design.

Mentorship is critical for faculty success, satisfaction, and engagement. However, many faculty, particularly underrepresented racial/ethnic (UR) faculty, lack access to high-quality mentoring. In an effort to improve mentoring for all faculty, we developed and implemented a formally structured faculty mentor training program (FMTP) across UC San Diego Health Sciences, which included institutional support, mentorship training, and department/division mentorship programs.

FMTP impact was evaluated using three primary outcome variables: mentoring quality, mentoring behaviors, and institutional climate. Participants’ self-assessed mentoring competencies were measured using validated instruments.

A total of 391 (23%) of Health Sciences faculty participated in FMTP. Participation rate was higher for women than men (30% versus 17%) and highest for UR faculty (39%). FMTP was implemented in 16 of 19 departments. Self-reported mentoring improved for FMTP participants with mentoring quality (p = 0.009) and meeting mentees’ expectations (p = 0.01) continuing to improve for up to 2 years after training. However, participants were unsure if they were meeting UR mentees’ expectations. FMTP participants were significantly more satisfied with mentoring quality (p < 0.001) compared to non-participants, with the greatest increase in satisfaction reported by UR faculty (38–61%). UR faculty reported improved overall morale (51–61%) and a perception that the environment was supportive for UR faculty (48–70%).

The implementation of a system-wide formal structured FMTP was associated with improved faculty satisfaction, quality of mentoring, and institutional climate, especially for UR faculty.

Scientific endeavors are increasingly carried out by teams of scientists. While there is growing literature on factors associated with effective science teams, little is known about processes that facilitate the success of dissemination and implementation (D&I) teams studying the uptake of healthcare innovations. This study aimed to identify strategies used by D&I scientists to promote team science.

Using a nominal group technique, a sample of 27 D&I scholars responded to the question, “What strategies have you or others used to promote team science?” Participants were asked to individually respond and then discuss within a small group to determine the group’s top three strategies. Through a facilitated consensus discussion with the full sample, a rank-ordered list of three strategies was determined.

A total of 126 individual responses (M = 9; SD = 4.88) were submitted. Through small group discussion, six groups ranked their top three strategies to promote team science. The final ranked list of strategies determined by the full sample included: (1) developing and maintaining clear expectations, (2) promoting and modeling effective communication, and (3) establishing shared goals and a mission of the work to be accomplished.

Because of its goal of translating knowledge to practice, D&I research necessitates the use of team science. The top strategies are in line with those found to be effective for teams in other fields and hold promise for improving D&I team cohesion and innovation, which may ultimately accelerate the translation of health innovations and the improvement of care quality and outcomes.

Translating research findings into practice requires understanding how to meet communication and dissemination needs and preferences of intended audiences including past research participants (PSPs) who want, but seldom receive, information on research findings during or after participating in research studies. Most researchers want to let others, including PSP, know about their findings but lack knowledge about how to effectively communicate findings to a lay audience.

We designed a two-phase, mixed methods pilot study to understand experiences, expectations, concerns, preferences, and capacities of researchers and PSP in two age groups (adolescents/young adults (AYA) or older adults) and to test communication prototypes for sharing, receiving, and using information on research study findings.

PSP and researchers agreed that sharing study findings should happen and that doing so could improve participant recruitment and enrollment, use of research findings to improve health and health-care delivery, and build community support for research. Some differences and similarities in communication preferences and message format were identified between PSP groups, reinforcing the best practice of customizing communication channel and messaging. Researchers wanted specific training and/or time and resources to help them prepare messages in formats to meet PSP needs and preferences but were unaware of resources to help them do so.

Our findings offer insight into how to engage both PSP and researchers in the design and use of strategies to share research findings and highlight the need to develop services and support for researchers as they aim to bridge this translational barrier.

Increased endogenous acetate production (Ra) in rodents has been shown to activate the parasympathetic nervous system and thereby promote increased glucose-stimulated insulin secretion (GSIS), increased ghrelin secretion, hyperphagia and obesity.

To examine whether rates of acetate turnover are different in lean versus obese humans and whether increased acetate turnover promotes increased GSIS and increased ghrelin secretion in humans.

Basal acetate Ra was measured following an overnight fast in lean (BMI: 21.3 ± 1.1 Kg/m2) and obese (30.2 ± 0.9 Kg/m2, P = 0.00001) individuals. The subjects underwent two hyperglycemic (10 mmol/L) clamp studies to measure GSIS during a basal acetate infusion and during a high-dose acetate infusion increasing plasma acetate concentrations ∼5-fold.

Basal acetate Ra was 30% higher in the lean compared to the obese subjects (257 ± 27 vs. 173 ± 18 μmol/min; P = 0.025). Basal plasma insulin concentrations were 4-fold higher in the obese than the lean subjects (P = 0.008) and increased 5-fold during hyperglycemia in both groups, independent of changes in plasma acetate concentrations. Fasting plasma ghrelin concentrations were 35% lower in the obese compared to the lean subjects (P = 0.015). During the hyperglycemic clamp, plasma ghrelin decreased by 42% in the lean group (P < 0.022 vs. basal) and did not change in the obese group.

Rates of endogenous acetate turnover are ∼30% higher in the lean subjects compared to the obese subjects, and increasing plasma acetate turnover does not promote increased GSIS or ghrelin secretion in either group.

Poor clinical trial (CT) recruitment is a significant barrier to translating basic science discoveries into medical practice. Improving support for primary care provider (PCP) referral of patients to CTs may be an important part of the solution. However, implementing CT referral support in primary care is not only technically challenging, but also presents challenges at the person and organization levels.

The objectives of this study were (1) to characterize provider and clinical supervisor attitudes and perceptions regarding CT research, recruitment, and referrals in primary care and (2) to identify perceived workflow strategies and facilitators relevant to designing a technology-supported primary care CT referral program. Focus groups were conducted with PCPs, directors, and supervisors.

Analysis indicated widespread support for the intrinsic scientific value of CTs, while at the same time deep concerns regarding protecting patient well-being, perceived loss of control when patients participate in trials, concern about the impact of point-of-care referrals on clinic workflow, the need for standard processes, and the need for CT information that enables referring providers to quickly confirm that the burdens are justified by the benefits at both patient and provider levels. PCP suggestions pertinent to implementing a CT referral decision support system are reported.

The results from this work contribute to developing an implementation approach to support increased referral of patients to CTs.

Personalized medicine has exposed wearable sensors as new sources of biomedical data which are expected to accrue annual data storage costs of approximately $7.2 trillion by 2020 (>2000 exabytes). To improve the usability of wearable devices in healthcare, it is necessary to determine the minimum amount of data needed for accurate health assessment.

Here, we present a generalizable optimization framework for determining the minimum necessary sampling rate for wearable sensors and apply our method to determine optimal optical blood volume pulse sampling rate. We implement t-tests, Bland–Altman analysis, and regression-based visualizations to identify optimal sampling rates of wrist-worn optical sensors.

We determine the optimal sampling rate of wrist-worn optical sensors for heart rate and heart rate variability monitoring to be 21–64 Hz, depending on the metric.

Determining the optimal sampling rate allows us to compress biomedical data and reduce storage needs and financial costs. We have used optical heart rate sensors as a case study for the connection between data volumes and resource requirements to develop methodology for determining the optimal sampling rate for clinical relevance that minimizes resource utilization. This methodology is extensible to other wearable sensors.

To enhance the performance evaluation of Clinical and Translational Science Award (CTSA) hubs, we examined the utility of advanced bibliometric measures that go beyond simple publication counts to demonstrate the impact of translational research output.

The sampled data included North Carolina Translational and Clinical Science Institute (NC TraCS)-supported publications produced between September 2008 and March 2017. We adopted advanced bibliometric measures and a state-of-the-art bibliometric network analysis tool to assess research productivity, citation impact, the scope of research collaboration, and the clusters of research topics.

Totally, 754 NC TraCS-supported publications generated over 24,000 citation counts by April 2017 with an average of 33 cites per article. NC TraCS-supported research papers received more than twice as many cites per year as the average National Institute of Health-funded research publications from the same field and time. We identified the top productive researchers and their networks within the CTSA hub. Findings demonstrated the impact of NC TraCS in facilitating interdisciplinary collaborations within the CTSA hub and across the CTSA consortium and connecting researchers with right peers and organizations.

Both improved bibliometrics measures and bibliometric network analysis can bring new perspectives to CTSA evaluation via citation influence and the scope of research collaborations.

Clinical trials, which are mainly conducted in urban medical centers, may be less accessible to rural residents. Our aims were to assess participation and the factors associated with participation of rural residents in clinical trials.

Using geocoding, the residential address of participants enrolled into clinical trials at Mayo Clinic locations in Arizona, Florida, and the Midwest between January 1, 2016, and December 31, 2017, was categorized as urban or rural. The distance travelled by participants and trial characteristics was compared between urban and rural participants. Ordinal logistic regression analyses were used to evaluate whether study location and risks were associated with rural participation in trials.

Among 292 trials, including 136 (47%) cancer trials, there were 2313 participants. Of these, 731 (32%) were rural participants, which is greater than the rural population in these 9 states (19%, P < 0.001). Compared to urban participants, rural participants were older (65 ± 12 years vs 64 ± 12 years, P = 0.004) and travelled further to the medical center (103 ± 104 vs 68 ± 88 miles, P < 0.001). The proportion of urban and rural participants who were remunerated was comparable. In the multivariable analysis, the proportion of rural participants was lower (P < 0.001) in Arizona (10%) and Florida (18%) than the Midwest (38%) but not significantly associated with the study-related risks.

Approximately one in three clinical trial participants were rural residents versus one in five in the population. Rural residents travelled further to access clinical trials. The study-associated risks were not associated with the distribution of rural and urban participants in trials.

Advancing understanding of human health promotion and disease prevention and treatment often requires teamwork. To evaluate academic medical institutions’ support for team science in the context of researchers’ career development, we measured the value placed on team science and specificity of guidance provided for documenting team science contributions in the promotion and tenure (P&T) documents of Colleges/Schools of Medicine (CoMs) in the National Center for Advancing Translational Sciences’ Clinical and Translational Science Award (CTSA) program.

We reviewed complete P&T documents from 57 of 63 CTSA CoMs to identify career paths defined by three dimensions: academic rank (associate versus full professor), tenure eligibility (tenure track versus not), and role (research, clinical, education, and administrative), and we rated team science value and documentation guidance for each path. Multilevel models were estimated to compare team science value and documentation guidance as a function of the three career path dimensions while accounting for the clustered data (N = 357 career paths within 57 CoMs).

Team science value was greater for associate than full professors, non-tenure-eligible versus tenure-eligible positions, and roles prioritizing clinical, education, and administrative responsibilities versus those prioritizing research. Guidance for documenting team science achievements was more explicit for roles that prioritized research.

Although P&T policies at most CTSA institutions express value for team science, inconsistent within-institutional patterns of recognition and reward across career paths may have implications for researchers’ involvement in team science. We discuss the implications of our findings for research and for P&T policies that promote team science.