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To evaluate the design of I-Corps@NCATS as a translational scientist training program, we mapped specific elements of the program’s content and pedagogy to the characteristics of a translational scientist, as first defined by Gilliland et al. []: systems thinker, process innovator, boundary spanner, team player, and skilled communicator. Using a mixed-methods evaluation, we examined how the I-Corps@NCATS training program, delivered across twenty-two Clinical and Translational Science Award Hubs, impacted the development of these key translational scientist characteristics.
Methods:
We developed survey items to assess the characteristics of systems thinker, process innovator, boundary spanner, team player, and skilled communicator. Data were collected from a national sample of 281 participants in the I-Corps@NCATS program. Using post-then-retrospective-pre survey items, participants self-reported their ability to perform skills associated with each of the translational scientist characteristics. Additionally, two open-ended survey questions explored how the program shifted participants’ translational orientation, generating 211 comments. These comments were coded through a team-based, iterative process.
Results:
Respondents reported the greatest increases in self-assessed abilities related to systems thinking and skilled communication. Participants indicated the highest levels of abilities related to team player and boundary crosser. From the coding of open-ended comments, we identified two additional characteristics of translational scientists: intellectual humility and cognitive flexibility.
Conclusions:
Participation in I-Corps@NCATS accelerates translational science in two ways: 1) by teaching the process of scientific translation from research ideas to real-world solutions, and 2) by encouraging growth in the mindset and characteristics of a translational scientist.
Clinical research requires a competent workforce of clinical research professionals (CRPs) who are well-trained to perform varied and complex tasks within their roles. The Joint Task Force for Clinical Trial Competency (JTF) framework established essential domains for conducting high-quality clinical research that can guide professional development of CRPs. The Research Professionals Network (RPN) Workshops were established in 2017 to focus on developing ongoing inter-institutional, peer-led, JTF-centric continuing education for CRPs. Four institutions and their affiliates are part of the collaboration.
Methods:
Workshop participant survey data and other metrics were collected over four academic years. Both quantitative and qualitative analyses were performed to assess participant experience and identify relevant themes.
Results:
Participants demonstrated overall high satisfaction with the workshops and significantly value the interpersonal, inter-institutional collaboration made possible through the workshops.
Conclusions:
These inter-institutional RPN Workshops have evolved into a Community of Practice, which can be expanded into future opportunities.
Although behavioral mechanisms in the association among depression, anxiety, and cancer are plausible, few studies have empirically studied mediation by health behaviors. We aimed to examine the mediating role of several health behaviors in the associations among depression, anxiety, and the incidence of various cancer types (overall, breast, prostate, lung, colorectal, smoking-related, and alcohol-related cancers).
Methods
Two-stage individual participant data meta-analyses were performed based on 18 cohorts within the Psychosocial Factors and Cancer Incidence consortium that had a measure of depression or anxiety (N = 319 613, cancer incidence = 25 803). Health behaviors included smoking, physical inactivity, alcohol use, body mass index (BMI), sedentary behavior, and sleep duration and quality. In stage one, path-specific regression estimates were obtained in each cohort. In stage two, cohort-specific estimates were pooled using random-effects multivariate meta-analysis, and natural indirect effects (i.e. mediating effects) were calculated as hazard ratios (HRs).
Results
Smoking (HRs range 1.04–1.10) and physical inactivity (HRs range 1.01–1.02) significantly mediated the associations among depression, anxiety, and lung cancer. Smoking was also a mediator for smoking-related cancers (HRs range 1.03–1.06). There was mediation by health behaviors, especially smoking, physical inactivity, alcohol use, and a higher BMI, in the associations among depression, anxiety, and overall cancer or other types of cancer, but effects were small (HRs generally below 1.01).
Conclusions
Smoking constitutes a mediating pathway linking depression and anxiety to lung cancer and smoking-related cancers. Our findings underline the importance of smoking cessation interventions for persons with depression or anxiety.
Autoimmune encephalitis is increasingly recognized as a neurologic cause of acute mental status changes with similar prevalence to infectious encephalitis. Despite rising awareness, approaches to diagnosis remain inconsistent and evidence for optimal treatment is limited. The following Canadian guidelines represent a consensus and evidence (where available) based approach to both the diagnosis and treatment of adult patients with autoimmune encephalitis. The guidelines were developed using a modified RAND process and included input from specialists in autoimmune neurology, neuropsychiatry and infectious diseases. These guidelines are targeted at front line clinicians and were created to provide a pragmatic and practical approach to managing such patients in the acute setting.
The present study investigates the interplay between proficiency and empathy in the development of second language (L2) prosody by analyzing the perception and processing of intonation in questions and statements in L2 Spanish. A total of 225 adult L2 Spanish learners (L1 English) from the Northeastern United States completed a two-alternative forced choice (2AFC) task in which they listened to four utterance types and categorized them as either questions or statements. We used Bayesian multilevel regression and drift diffusion modeling to analyze the 2AFC data as a function of proficiency level and empathy scores for each utterance type. We show that learner response accuracy and sensitivity to intonation are positively correlated with proficiency, and this association is affected by individual empathy levels in both response accuracy and sentence processing. Higher empathic individuals, in comparison with lower empathic individuals, appear to be more sensitive to intonation cues in the process of forming sound-meaning associations, though increased sensitivity does not necessarily imply increased processing speed. The results motivate the inclusion of measures of pragmatic skill, such as empathy, to better account for intonational meaning processing and sentence comprehension in second language acquisition.
To define the incidence of definitive necrotising enterocolitis in term infants with CHD and identify risk factors for morbidity/mortality.
Methods:
We performed a 20-year (2000–2020) single-institution retrospective cohort study of term infants with CHD admitted to the Boston Children’s Hospital cardiac ICU with necrotising enterocolitis (Bell’s stage ≥ II). The primary outcome was a composite of in-hospital mortality and post-necrotising enterocolitis morbidity (need for extracorporeal membrane oxygenation, multisystem organ failure based on the paediatric sequential organ failure assessment score, and/or need for acute gastrointestinal intervention). Predictors included patient characteristics, cardiac diagnosis/interventions, feeding regimen, and severity measures.
Results:
Of 3933 term infants with CHD, 2.1% (n = 82) developed necrotising enterocolitis, with 67% diagnosed post-cardiac intervention. Thirty (37%) met criteria for the primary outcome. In-hospital mortality occurred in 14 infants (17%), of which nine (11%) deaths were attributable to necrotising enterocolitis. Independent predictors of the primary outcome included moderate to severe systolic ventricular dysfunction (odds ratio 13.4,confidence intervals 1.13–159) and central line infections pre-necrotising enterocolitis diagnosis (odds ratio 17.7, confidence intervals 3.21–97.0) and mechanical ventilation post-necrotising enterocolitis diagnosis (odds ratio 13.5, confidence intervals 3.34–54.4). Single ventricle, ductal dependency, and feeding related factors were not independently associated with the primary outcome.
Conclusions:
The incidence of necrotising enterocolitis was 2.1% in term infants with CHD. Adverse outcomes occurred in greater than 30% of patients. Presence of systolic dysfunction and central line infections prior to diagnosis and need for mechanical ventilation after diagnosis of necrotising enterocolitis can inform risk triage and prognostic counseling for families.
Midcareer research faculty are a vital part of the advancement of science in U.S. medical schools, but there are troubling trends in recruitment, retention, and burnout rates.
Methods:
The primary sampling frame for this online survey was recipients of a single R01 or equivalent and/or K-award from 2013 to 2019. Inclusion criteria were 3–14 years at a U.S. medical school and rank of associate professor or two or more years as assistant professor. Forty physician investigators and Ph.D. scientists volunteered for a faculty development program, and 106 were propensity-matched controls. Survey items covered self-efficacy in career, research, work-life; vitality/burnout; relationships, inclusion, trust; diversity; and intention to leave academic medicine.
Results:
The majority (52%) reported receiving poor mentoring; 40% experienced high burnout and 41% low vitality, which, in turn, predicted leaving intention (P < 0.0005). Women were more likely to report high burnout (P = 0.01) and low self-efficacy managing work and personal life (P = 0.01) and to be seriously considering leaving academic medicine than men (P = 0.003). Mentoring quality (P < 0.0005) and poor relationships, inclusion, and trust (P < 0.0005) predicted leaving intention. Non-underrepresented men were very likely to report low identity self-awareness (65%) and valuing differences (24%) versus underrepresented men (25% and 0%; P < 0.0005). Ph.D.s had lower career advancement self-efficacy than M.D.s (P < .0005).
Conclusions:
Midcareer Ph.D. and physician investigators faced significant career challenges. Experiences diverged by underrepresentation, gender, and degree. Poor quality mentoring was an issue for most. Effective mentoring could address the concerns of this vital component of the biomedical workforce.
Interprofessional healthcare team function is critical to the effective delivery of patient care. Team members must possess teamwork competencies, as team function impacts patient, staff, team, and healthcare organizational outcomes. There is evidence that team training is beneficial; however, consensus on the optimal training content, methods, and evaluation is lacking. This manuscript will focus on training content. Team science and training research indicates that an effective team training program must be founded upon teamwork competencies. The Team FIRST framework asserts there are 10 teamwork competencies essential for healthcare providers: recognizing criticality of teamwork, creating a psychologically safe environment, structured communication, closed-loop communication, asking clarifying questions, sharing unique information, optimizing team mental models, mutual trust, mutual performance monitoring, and reflection/debriefing. The Team FIRST framework was conceptualized to instill these evidence-based teamwork competencies in healthcare professionals to improve interprofessional collaboration. This framework is founded in validated team science research and serves future efforts to develop and pilot educational strategies that educate healthcare workers on these competencies.
Profitability, yield, and fertilizer use are compared across three different potassium (K) fertilizer rate recommendation ideologies. Existing agronomic, “build and maintain” rate recommendations (KE) are compared to profit-maximizing rates with and without taking long-run soil-test K (STK) implications into account. Regardless of starting STK, K use equilibrated over the course of 3 years irrespective of ideology. Since taking long-run STK into account did not alter ending STK and only led to a miniscule yield effect, we encourage producers to use annual profit-maximizing K rates that were 3–11% lower than KE rates and generated more profit with minimal yield loss.
The goal of clinical and translational science (CTS) is to fill gaps in medical knowledge toward improving human health. However, one of our most pressing challenges does not reside within the biological map we navigate to find sustainable cures but rather the moral compass to recognize and overcome racial and ethnic injustices that continue to influence our society and hinder diverse research rigor. The Georgetown-Howard Universities Center for Clinical and Translational Science includes an inter-institutional TL1-funded training program for predoctoral/postdoctoral trainees in Translational Biomedical Science (TBS).
Methods:
In the fall of 2020, the TBS program responded to the national social justice crisis by incorporating a curriculum focused on structural racism in biomedical research. Educational platforms, including movie reviews, Journal Clubs, and other workshops, were threaded throughout the curriculum by ensuring safe spaces to discuss racial and ethnic injustices and providing trainees with practical steps to recognize, approach, and respond to these harmful biases in the CTS. Workshops also focused on why individuals underrepresented in science are vital for addressing and closing gaps in CTS.
Results:
Paring analysis using REDCap software de-identified participants after invitations were sent and collected in the system to maintain anonymity for pre- and post-analysis. The Likert scale evaluated respondents’ understanding of diverse scientific circumstances. The pre/Fall and post/Spring surveys suggested this curriculum was successful at raising institutional awareness of racial and ethnic biases. Evaluating the effectiveness of our program with other training Clinical and Translational Science Awards (CTSA) consortiums will strengthen both the academic and professional TBS programs.
As the COVID-19 pandemic took hold in the USA in early 2020, it became clear that knowledge of the prevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among asymptomatic individuals could inform public health policy decisions and provide insight into the impact of the infection on vulnerable populations. Two Clinical and Translational Science Award (CTSA) Hubs and the National Institutes of Health (NIH) set forth to conduct a national seroprevalence survey to assess the infection’s rate of spread. This partnership was able to quickly design and launch the project by leveraging established research capacities, prior experiences in large-scale, multisite studies and a highly skilled workforce of CTSA hubs and unique experimental capabilities at the NIH to conduct a diverse prospective, longitudinal observational cohort of 11,382 participants who provided biospecimens and participant-reported health and behavior data. The study was completed in 16 months and benefitted from transdisciplinary teamwork, information technology innovations, multimodal communication strategies, and scientific partnership for rigor in design and analytic methods. The lessons learned by the rapid implementation and dissemination of this national study is valuable in guiding future multisite projects as well as preparation for other public health emergencies and pandemics.
In this study, we used genomic sequencing to identify variants of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) in healthcare workers with coronavirus disease 2019 (COVID-19) after receiving a booster vaccination. We compared symptoms, comorbidities, exposure risks, and vaccine history between the variants. Postbooster COVID-19 cases increased as the SARS-CoV-2 omicron variant predominated.
OBJECTIVES/GOALS: The goal of this study was to understand the impact of a high sodium diet on gene networks in the kidney that correlate with blood pressure in female primates, and translating findings to women. METHODS/STUDY POPULATION: Sodium-naïve female baboons (n=7) were fed a low-sodium (LS) diet for 6 weeks followed by a high sodium (HS) diet for 6 weeks. Sodium intake, serum 17 beta-estradiol, and ultrasound-guided kidney biopsies for RNA-Seq were collected at the end of each diet. Blood pressure was continuously measured for 64-hour periods throughout the study by implantable telemetry devices. Weighted gene coexpression network analysis was performed on RNA-Seq data to identify transcripts correlated with blood pressure on each diet. Network analysis was performed on transcripts highly correlated with BP, and in silico findings were validated by immunohistochemistry of kidney tissues. RESULTS/ANTICIPATED RESULTS: On the LS diet, Na+ intake and serum 17 beta-estradiol concentration correlated with BP. Cell type composition of renal biopsies was consistent among all animals for both diets. Kidney transcriptomes differed by diet; analysis by unbiased weighted gene co-expression network analysis revealed modules of genes correlated with BP on the HS diet. Network analysis of module genes showed causal networks linking hormone receptors, proliferation and differentiation, methylation, hypoxia, insulin and lipid regulation, and inflammation as regulators underlying variation in BP on the HS diet. Our results show variation in BP correlated with novel kidney gene networks with master regulators PPARG and MYC in female baboons on a HS diet. DISCUSSION/SIGNIFICANCE: Previous studies in primates to identify molecular networks dysregulated by HS diet focused on males. Current clinical guidelines do not offer sex-specific treatment plans for sodium sensitive hypertension. This study leveraged variation in BP as a first step to identify correlated kidney regulatory gene networks in female primates after a HS diet.
This study assessed the extent to which women's preconception binge drinking, tobacco use and cannabis use, reported prospectively in adolescence and young adulthood, predicted use of these substances during pregnancy and at 1 year postpartum.
Methods
Data were pooled from two intergenerational cohort studies: the Australian Temperament Project Generation 3 Study (395 mothers, 691 pregnancies) and the Victorian Intergenerational Health Cohort Study (398 mothers, 609 pregnancies). Alcohol, tobacco and cannabis use were assessed in adolescence (13–18 years), young adulthood (19–29 years) and at ages 29–35 years for those transitioning to parenthood. Exposures were weekly or more frequent preconception binge drinking (5 + drinks in one session), tobacco use and cannabis use. Outcomes were any alcohol, tobacco and cannabis use prior to awareness of the pregnancy, after awareness of pregnancy (up to and including the third trimester pregnancy) and at 1 year postpartum.
Results
Frequent preconception binge drinking, tobacco use and cannabis use across both adolescence and young adulthood were strong predictors of continued use post-conception, before and after awareness of the pregnancy and at 1 year postpartum. Substance use limited to young adulthood also predicted continued use post-conception.
Conclusions
Persistent alcohol, tobacco use and cannabis use that starts in adolescence has a strong continuity into parenthood. Reducing substance use in the perinatal period requires action well before pregnancy, commencing in adolescence and continuing into the years before conception and throughout the perinatal period.
The 2020 COVID-19 pandemic has had a profound impact on the clinical research enterprises at the 60 Clinical and Translational Science Award (CTSA) Hubs throughout the nation. There was simultaneously a need to expand research to obtain crucial data about disease prognosis and therapy and enormous limitations on conducting research as localities and institutions limited travel and person-to-person contact. These imperatives resulted in major changes in the way research was conducted, including expediting Institutional Review Board review, shifting to remote interactions with participants, centralizing decision-making in prioritizing research protocols, establishing biobanks, adopting novel informatics platforms, and distributing study drugs in unconventional ways. National CTSA Steering Committee meetings provided an opportunity to share best practices and develop the idea of capturing the CTSA program experiences in a series of papers. Here we bring together the recommendations from those papers in a list of specific actions that research sites can take to strengthen operations and prepare for similar future public health emergencies. Most importantly, creative innovations developed in response to the COVID-19 pandemic deserve serious consideration for adoption as new standards, thus converting the painful trauma of the pandemic into “post-traumatic growth” that makes the clinical research enterprise stronger, more resilient, and more effective.
Biospecimen repositories play a vital role in enabling investigation of biologic mechanisms, identification of disease-related biomarkers, advances in diagnostic assays, recognition of microbial evolution, and characterization of new therapeutic targets for intervention. They rely on the complex integration of scientific need, regulatory oversight, quality control in collection, processing and tracking, and linkage to robust phenotype information. The COVID-19 pandemic amplified many of these considerations and illuminated new challenges, all while academic health centers were trying to adapt to unprecedented clinical demands and heightened research constraints not witnessed in over 100 years. The outbreak demanded rapid understanding of SARS-CoV-2 to develop diagnostics and therapeutics, prompting the immediate need for access to high quality, well-characterized COVID-19-associated biospecimens. We surveyed 60 Clinical and Translational Science Award (CTSA) hubs to better understand the strategies and barriers encountered in biobanking before and in response to the COVID-19 pandemic. Feedback revealed a major shift in biorepository model, specimen-acquisition and consent process from a combination of investigator-initiated and institutional protocols to an enterprise-serving strategy. CTSA hubs were well equipped to leverage established capacities and expertise to quickly respond to the scientific needs of this crisis through support of institutional approaches in biorepository management.