From goal to outcome: Analyzing the progression of biomedical sciences PhD careers in a longitudinal study using an expanded taxonomy.

Biomedical sciences PhDs pursue a wide range of careers inside and outside academia. However, there is little data regarding how career interests of PhD students relate to the decision to pursue postdoctoral training or to their eventual career outcomes. Here, we present the career goals and career outcomes of 1452 biomedical sciences PhDs who graduated from Vanderbilt University between 1997 and 2021. We categorized careers using an expanded three-tiered taxonomy and flags that delineate key career milestones. We also analyzed career goal changes between matriculation and doctoral defense, and the reasons why students became more- or less-interested in research-intensive faculty careers. We linked students' career goal at doctoral defense to whether they did a postdoc, the duration of time between doctoral defense and the first non-training position, the career area of the first non-training position, and the career area of the job at 10 years after graduation. Finally, we followed individual careers for 10 years after graduation to characterize movement between different career areas over time. We found that most students changed their career goal during graduate school, declining numbers of alumni pursued postdoctoral training, many alumni entered first non-training positions in a different career area than their goal at doctoral defense, and the career area of the first non-training position was a good indicator of the job that alumni held 10 years after graduation. Our findings emphasize that students need a wide range of career development opportunities and career mentoring during graduate school to prepare them for futures in research and research-related professions.

Biomedical graduate student experiences during the COVID-19 university closure.

COVID-19-associated university closures moved classes online and interrupted ongoing research in universities throughout the US. In Vanderbilt University, first year biomedical sciences PhD students were in the middle of their spring semester coursework and in the process of identifying a thesis research lab, while senior students who had already completed the first year were at various stages of their graduate training and were working on their thesis research projects. To learn how the university closure and resulting interruptions impacted our students' learning and well-being, we administered two surveys, one to the first year students and the other to the senior students. Our main findings show that the university closure negatively impacted the overall psychological health of about one-third of the survey respondents, time management was the aspect of remote learning that caused the highest stress for close to 50% of the students, and interaction with their peers and in-person discussions were the aspects of on-campus learning that students missed the most during the remote learning period. Additionally, survey responses also show that students experienced positive outcomes as a result of remote learning that included spending increased time on additional learning interests, with family, on self-care, and for dissertation or manuscript writing. Though a variety of supportive resources are already available to students in our institution, results from our survey suggest enhancing these measures and identifying new ones targeted to addressing the academic and emotional needs of PhD students would be beneficial. Such support measures may be appropriate for students in other institutions as well.

A cross-institutional analysis of the effects of broadening trainee professional development on research productivity.

PhD-trained scientists are essential contributors to the workforce in diverse employment sectors that include academia, industry, government, and nonprofit organizations. Hence, best practices for training the future biomedical workforce are of national concern. Complementing coursework and laboratory research training, many institutions now offer professional training that enables career exploration and develops a broad set of skills critical to various career paths. The National Institutes of Health (NIH) funded academic institutions to design innovative programming to enable this professional development through a mechanism known as Broadening Experiences in Scientific Training (BEST). Programming at the NIH BEST awardee institutions included career panels, skill-building workshops, job search workshops, site visits, and internships. Because doctoral training is lengthy and requires focused attention on dissertation research, an initial concern was that students participating in additional complementary training activities might exhibit an increased time to degree or diminished research productivity. Metrics were analyzed from 10 NIH BEST awardee institutions to address this concern, using time to degree and publication records as measures of efficiency and productivity. Comparing doctoral students who participated to those who did not, results revealed that across these diverse academic institutions, there were no differences in time to degree or manuscript output. Our findings support the policy that doctoral students should participate in career and professional development opportunities that are intended to prepare them for a variety of diverse and important careers in the workforce.

Applying inter-rater reliability to improve consistency in classifying PhD career outcomes.

Background: There has been a groundswell of national support for transparent tracking and dissemination of PhD career outcomes. In 2017, individuals from multiple institutions and professional organizations met to create the Unified Career Outcomes Taxonomy (UCOT 2017), a three-tiered taxonomy to help institutions uniformly classify career outcomes of PhD graduates. Early adopters of UCOT 2017, noted ambiguity in some categories of the career taxonomy, raising questions about its consistent application within and across institutions. Methods: To test and evaluate the consistency of UCOT 2017, we calculated inter-rater reliability across two rounds of iterative refinement of the career taxonomy, classifying over 800 PhD alumni records via nine coders. Results: We identified areas of discordance in the taxonomy, and progressively refined UCOT 2017 and an accompanying Guidance Document to improve inter-rater reliability across all three tiers of the career taxonomy. However, differing interpretations of the classifications, especially for faculty classifications in the third tier, resulted in continued discordance among the coders. We addressed this discordance with clarifying language in the Guidance Document, and proposed the addition of a flag system for identification of the title, rank, and prefix of faculty members. This labeling system provides the additional benefit of highlighting the granularity and the intersectionality of faculty job functions, while maintaining the ability to sort by - and report data on - faculty and postdoctoral trainee roles, as is required by some national and federal reporting guidelines. We provide specific crosswalk guidance for how a user may choose to incorporate our suggestions while maintaining the ability to report in accordance with UCOT 2017. Conclusions: Our findings underscore the importance of detailed guidance documents, coder training, and periodic collaborative review of career outcomes taxonomies as PhD careers evolve in the global workforce. Implications for coder-training and use of novice coders are also discussed.

Faculty perceptions and knowledge of career development of trainees in biomedical science: What do we (think we) know?

The Broadening Experiences in Scientific Training (BEST) program is an NIH-funded effort testing the impact of career development interventions (e.g. internships, workshops, classes) on biomedical trainees (graduate students and postdoctoral fellows). BEST Programs seek to increase trainees' knowledge, skills and confidence to explore and pursue expanded career options, as well as to increase training in new skills that enable multiple career pathways. Faculty mentors are vital to a trainee's professional development, but data about how faculty members of biomedical trainees view the value of, and the time spent on, career development are lacking. Seven BEST institutions investigated this issue by conducting faculty surveys during their BEST experiment. The survey intent was to understand faculty perceptions around professional and career development for their trainees. Two different, complementary surveys were employed, one designed by Michigan State University (MSU) and the other by Vanderbilt University. Faculty (592) across five institutions responded to the MSU survey; 225 faculty members from two institutions responded to the Vanderbilt University survey. Participating faculty were largely tenure track and male; approximately 1/3 had spent time in a professional position outside of academia. Respondents felt a sense of urgency in introducing broad career activities for trainees given a recognized shortage of tenure track positions. They reported believing career development needs are different between a graduate student and postdoctoral fellow, and they indicated that they actively mentor trainees in career development. However, faculty were uncertain as to whether they actually have the knowledge or training to do so effectively. Faculty perceived that trainees themselves lack a knowledge base of skills that are of interest to non-academic employers. Thus, there is a need for exposure and training in such skills. Faculty stated unequivocally that institutional support for career development is important and needed. BEST Programs were considered beneficial to trainees, but the awareness of local BEST Programs and the national BEST Consortium was low at the time surveys were employed at some institutions. It is our hope that the work presented here will increase the awareness of the BEST national effort and the need for further career development for biomedical trainees.

Survey of checkpoints along the pathway to diverse biomedical research faculty.

There is a persistent shortage of underrepresented minority (URM) faculty who are involved in basic biomedical research at medical schools. We examined the entire training pathway of potential candidates to identify the points of greatest loss. Using a range of recent national data sources, including the National Science Foundation's Survey of Earned Doctorates and Survey of Doctoral Recipients, we analyzed the demographics of the population of interest, specifically those from URM backgrounds with an interest in biomedical sciences. We examined the URM population from high school graduates through undergraduate, graduate, and postdoctoral training as well as the URM population in basic science tenure track faculty positions at medical schools. We find that URM and non-URM trainees are equally likely to transition into doctoral programs, to receive their doctoral degree, and to secure a postdoctoral position. However, the analysis reveals that the diversions from developing a faculty career are found primarily at two clearly identifiable places, specifically during undergraduate education and in transition from postdoctoral fellowship to tenure track faculty in the basic sciences at medical schools. We suggest focusing additional interventions on these two stages along the educational pathway.

Training the next generation of physician researchers - Vanderbilt Medical Scholars Program.

BACKGROUND: As highlighted in recent reports published by the Physician-Scientist Workforce Working Group at the National Institutes of Health, the percentage of physicians conducting research has declined over the past decade. Various programs have been put in place to support and develop current medical student interest in research to alleviate this shortage, including The Vanderbilt University School of Medicine Medical Scholars Program (MSP). This report outlines the long-term program goals and short-term outcomes on career development of MSP alumni, to shed light on the effectiveness of research training programs during undergraduate medical training to inform similar programs in the United States. METHODS: MSP alumni were asked to complete an extensive survey assessing demographics, accomplishments, career progress, future career plans, and MSP program evaluation. RESULTS: Fifty-five (81%) MSP alumni responded, among whom 12 had completed all clinical training. The demographics of MSP alumni survey respondents are similar to those of all Vanderbilt medical students and medical students at all other Association of American Medical College (AAMC) medical schools. MSP alumni published a mean of 1.9 peer-reviewed manuscripts (95% CI:1.2, 2.5), and 51% presented at national meetings. Fifty-eight percent of respondents reported that MSP participation either changed their career goals or helped to confirm or refine their career goals. CONCLUSIONS: Results suggest that the MSP program both prepares students for careers in academic medicine and influences their career choices at an early juncture in their training. A longer follow-up period is needed to fully evaluate the long-term outcomes of some participants.

Providing Experiential Business and Management Training for Biomedical Research Trainees.

Many biomedical PhD trainees lack exposure to business principles, which limits their competitiveness and effectiveness in academic and industry careers. To fill this training gap, we developed Business and Management Principles for Scientists, a semester-long program that combined didactic exposure to business fundamentals with practical team-based projects aimed at solving real business problems encountered by institutional shared--resource core facilities. The program also included a retreat featuring presentations by and networking with local life science entrepreneurs and final team presentations to expert judges. Quantitative and qualitative metrics were used to evaluate the program's impact on trainees. A pretest-posttest approach was used to assess trainees' baseline knowledge and mastery of module concepts, and each individual's pretest and posttest responses were compared. The mean score improved by more than 17 percentage points. Trainees also took an online survey to provide feedback about the module. Nearly all participants agreed or strongly agreed that the module was a valuable use of their time and will help guide their career decisions and that project work helped drive home module concepts. More than 75% of trainees reported discussing the module with their research advisors, and all of these participants reported supportive or neutral responses. Collectively, the trainee feedback about the module, improvement in test scores, and trainee perception of advisor support suggest that this short module is an effective method of providing scientists with efficient and meaningful exposure to business concepts.

The Limitations of the GRE in Predicting Success in Biomedical Graduate School.

Historically, admissions committees for biomedical Ph.D. programs have heavily weighed GRE scores when considering applications for admission. The predictive validity of GRE scores on graduate student success is unclear, and there have been no recent investigations specifically on the relationship between general GRE scores and graduate student success in biomedical research. Data from Vanderbilt University Medical School's biomedical umbrella program were used to test to what extent GRE scores can predict outcomes in graduate school training when controlling for other admissions information. Overall, the GRE did not prove useful in predicating who will graduate with a Ph.D., pass the qualifying exam, have a shorter time to defense, deliver more conference presentations, publish more first author papers, or obtain an individual grant or fellowship. GRE scores were found to be moderate predictors of first semester grades, and weak to moderate predictors of graduate GPA and some elements of a faculty evaluation. These findings suggest admissions committees of biomedical doctoral programs should consider minimizing their reliance on GRE scores to predict the important measures of progress in the program and student productivity.

Survey of Asian patients with hepatitis B infection: limited knowledge of transmission and screening of family members.

Asian American families are disproportionately affected by Hepatitis B (HBV) infection. We aimed to assess the extent of screening family members of Asian patients with known HBV infection as well as patients' knowledge of HBV disease. A cross-sectional survey of established Asian patients with HBV-infection was performed at a university liver clinic. Outcome measures included the percentage of family members whose HBV serostatus was unknown and the percentage of patients who were able to correctly identify modes of transmission. A total of 803 US-based family members were identified by 58 patients. Patients did not know the HBV serostatus of 50% of their family members and 28% of their immediate family members. Fifty percent of participants did not know how they had acquired HBV or stated unlikely transmission modes. Though nationwide vaccination campaigns target this underrepresented population, screening family members of Asian patients with HBV remains a challenge.

Differential association of postsynaptic signaling protein complexes in striatum and hippocampus.

Distinct physiological stimuli are required for bidirectional synaptic plasticity in striatum and hippocampus, but differences in the underlying signaling mechanisms are poorly understood. We have begun to compare levels and interactions of key excitatory synaptic proteins in whole extracts and subcellular fractions isolated from micro-dissected striatum and hippocampus. Levels of multiple glutamate receptor subunits, calcium/calmodulin-dependent protein kinase II (CaMKII), a highly abundant serine/threonine kinase, and spinophilin, a F-actin and protein phosphatase 1 (PP1) binding protein, were significantly lower in striatal extracts, as well as in synaptic and/or extrasynaptic fractions, compared with similar hippocampal extracts/fractions. However, CaMKII interactions with spinophilin were more robust in striatum compared with hippocampus, and this enhanced association was restricted to the extrasynaptic fraction. NMDAR GluN2B subunits associate with both spinophilin and CaMKII, but spinophilin-GluN2B complexes were enriched in extrasynaptic fractions whereas CaMKII-GluN2B complexes were enriched in synaptic fractions. Notably, the association of GluN2B with both CaMKII and spinophilin was more robust in striatal extrasynaptic fractions compared with hippocampal extrasynaptic fractions. Selective differences in the assembly of synaptic and extrasynaptic signaling complexes may contribute to differential physiological regulation of excitatory transmission in striatum and hippocampus.

Centralized oversight of physician-scientist faculty development at Vanderbilt: early outcomes.

PURPOSE: In 2000, faced with a national concern over the decreasing number of physician-scientists, Vanderbilt School of Medicine established the institutionally funded Vanderbilt Physician-Scientist Development (VPSD) program to provide centralized oversight and financial support for physician-scientist career development. In 2002, Vanderbilt developed the National Institutes of Health (NIH)-funded Vanderbilt Clinical Research Scholars (VCRS) program using a similar model of centralized oversight. The authors evaluate the impact of the VPSD and VCRS programs on early career outcomes of physician-scientists. METHOD: Physician-scientists who entered the VPSD or VCRS programs from 2000 through 2006 were compared with Vanderbilt physician-scientists who received NIH career development funding during the same period without participating in the VPSD or VCRS programs. RESULTS: Seventy-five percent of VPSD and 60% of VCRS participants achieved individual career award funding at a younger age than the comparison cohort. This shift to career development award funding at a younger age among VPSD and VCRS scholars was accompanied by a 2.6-fold increase in the number of new K awards funded and a rate of growth in K-award dollars at Vanderbilt that outpaced the national rate of growth in K-award funding. CONCLUSIONS: Analysis of the early outcomes of the VPSD and VCRS programs suggests that centralized oversight can catalyze growth in the number of funded physician-scientists at an institution. Investment in this model of career development for physician-scientists may have had an additive effect on the recruitment and retention of talented trainees and junior faculty.

Association of protein phosphatase 1 gamma 1 with spinophilin suppresses phosphatase activity in a Parkinson disease model.

Sustained nigrostriatal dopamine depletion increases the serine/threonine phosphorylation of multiple striatal proteins that play a role in corticostriatal synaptic plasticity, including Thr(286) phosphorylation of calcium/calmodulin-dependent protein kinase IIalpha (CaMKIIalpha). Mechanisms underlying these changes are unclear, but protein phosphatases play a critical role in the acute modulation of striatal protein phosphorylation. Here we show that dopamine depletion for periods ranging from 3 weeks to 10 months significantly reduces the total activity of protein phosphatase (PP) 1, but not of PP2A, in whole lysates of rat striatum, as measured using multiple substrates, including Thr(286)-autophosphorylated CaMKIIalpha. Striatal PP1 activity is partially inhibited by a fragment of the PP1-binding protein neurabin-I, Nb-(146-493), because of the selective inhibition of the PP1gamma(1) isoform. The fraction of PP1 activity that is insensitive to Nb-(146-493) was unaffected by dopamine depletion, demonstrating that dopamine depletion specifically reduces the activity of PP1 isoforms that are sensitive to Nb-(146-493) (i.e. PP1gamma(1)). However, total striatal levels of PP1gamma(1) or any other PP1 isoform were unaffected by dopamine depletion, and our previous studies showed that total levels of the PP1 regulatory/targeting proteins DARPP-32, spinophilin, and neurabin were also unchanged. Rather, co-immunoprecipitation experiments demonstrated that dopamine depletion increases the association of PP1gamma(1) with spinophilin in striatal extracts. In combination, these data demonstrate that striatal dopamine depletion inhibits a specific synaptic phosphatase by increasing PP1gamma(1) interaction with spinophilin, perhaps contributing to hyperphosphorylation of synaptic proteins and disruptions of synaptic plasticity and/or dendritic morphology.

Dopamine depletion alters phosphorylation of striatal proteins in a model of Parkinsonism.

Nigrostriatal dopamine depletion disrupts striatal medium spiny neuron morphology in Parkinson's disease and modulates striatal synaptic plasticity in animal models of parkinsonism. We demonstrate that long-term nigrostriatal dopamine depletion in the rat induces evolving changes in the phosphorylation of striatal proteins critical for synaptic plasticity. Dopamine depletion increased the phosphorylation of the alpha isoform of calcium-calmodulin-dependent protein kinase II (CaMKIIalpha) at Thr286, a site associated with enhanced autonomous kinase activity, but did not alter total levels of CaMKIIalpha or other synaptic proteins. Dopamine depletion decreased CaMKIIalpha levels in postsynaptic density-enriched fractions without significant changes in other proteins. The activity of protein phosphatase 1 (PP1), a postsynaptic phosphatase that dephosphorylates CaMKII, is regulated by DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of 32 kDa). Dopamine depletion had no effect on DARPP-32 phosphorylation at Thr34, but increased DARPP-32 phosphorylation at Thr75. Levodopa administration reversed the increased phosphorylation of both CaMKIIalpha and DARPP-32. Normal ageing increased the levels of PP1(gamma1 isoform) but decreased levels of the PP1gamma1-targeting proteins spinophilin and neurabin. Elevated phosphorylations of CaMKIIalpha and DARPP-32 were maintained for up to 20 months after dopamine depletion. However, phosphorylation of the CaMKII-PP1 substrate, Ser831 in the glutamate receptor GluR1 subunit, was increased only after sustained (9-20 months) dopamine depletion. Interaction of ageing-related changes in PP1 with the dopamine depletion-induced changes in CaMKIIalpha may account for enhanced GluR1 phosphorylation only after long-term dopamine depletion. These evolving changes may impact striatal synaptic plasticity, Parkinson's disease progression and the changing efficacy and side-effects associated with dopamine replacement therapy.

Calcium/calmodulin-dependent protein kinase II and synaptic plasticity.

A prominent role for calcium/calmodulin-dependent protein kinase II (CaMKII) in regulation of excitatory synaptic transmission was proposed two decades ago when it was identified as a major postsynaptic density protein. Since then, fascinating mechanisms optimized to fine-tune the magnitude and locations of CaMKII activity have been revealed. The importance of CaMKII activity and autophosphorylation to synaptic plasticity in vitro, and to a variety of learning and memory paradigms in vivo has been demonstrated. Recent progress brings us closer to understanding the regulation of dendritic CaMKII activity, localization, and expression, and its role in modulating synaptic transmission and cell morphology.