A Research Operations, Management, and Strategy Fellowship for Life Sciences PhD Graduates.

PROBLEM: With less than 25% of PhD-trained scientists in the United States securing a tenure-track faculty position following training, nonacademic careers have become common. As the academic research enterprise has increased, business-oriented careers have emerged. The Research Operations, Management, and Strategy (ROMS) Fellowship was developed to increase awareness of and prepare life sciences PhD graduates for business-focused careers. APPROACH: The ROMS Fellowship was developed from March through December 2018 by the University of Michigan Medical School. Launched in 2019 and based on real-world experiences, the 2-year ROMS Fellowship combines immersion rotations and project work to develop an understanding of foundational infrastructure across the full spectrum of research. OUTCOMES: From 2019 to 2022, there were 4 ROMS Fellowship recruitment cycles, with a mean of 7 applicants per cycle and 2 fellows selected each year. Of the 8 fellows recruited, 5 (62.5%) joined directly from PhD training, whereas 3 (37.5%) had 2 to 6 years of postdoctoral training. Fellows have worked with 26 departments on 44 rotation projects and 30 impact projects and self-reported significant skill development in communicating with diverse stakeholders, strategic thinking, using new tools and resources, developing and scoping a project plan, and managing and leading a project. To date, 4 fellows have completed the program and were hired immediately into full-time positions at the University of Michigan Medical School. NEXT STEPS: Early feedback indicates that the program has been well received and effective. Previously, program refinement was directed by qualitative input from fellows and unit directors. However, for future cohorts, assessment tools will be implemented to capture qualitative and quantitative data to measure acquired skills and how program components contribute to professional development and career placement. A longitudinal follow-up will also be conducted with program alumni to track longer-term outcomes and career pathways.

Award rate inequities in biomedical research.

PURPOSE: The analysis of existing institutional research proposal databases can provide novel insights into science funding parity. The purpose of this study was to analyze the relationship between race/ethnicity and extramural research proposal and award rates across a medical school faculty and to determine whether there was evidence that researchers changed their submission strategies because of differential inequities across submission categories. METHOD: The authors performed an analysis of 14,263 biomedical research proposals with proposed start dates between 2010-2022 from the University of Michigan Medical School, measuring the proposal submission and award rates for each racial/ethnic group across 4 possible submission categories (R01 & Equivalent programs, other federal, industry, and non-profit). RESULTS: Researchers from each self-identified racial/ethnic group (Asian, Black/African American, Hispanic/Latino) pursued a different proposal submission strategy than the majority group (White). The authors found that Black/African American researchers experienced negative award rate differentials across all submission categories, which resulted in the lowest R01 & Equivalent and Other Federal submission rates of any racial/ethnic group and the highest submission rate to non-profit sources. The authors did not find support for the hypothesis that researchers changed submission strategies in response to award rate inequalities across submission categories. CONCLUSIONS: Biomedical researchers from different racial/ethnic groups follow markedly different proposal submission strategies within the University of Michigan Medical School. There is also a clear relationship between race/ethnicity and rates of proposal award. Black/African American and Asian researchers appear disadvantaged across all submission categories relative to White researchers. This study can be easily replicated by other academic research institutions, revealing opportunities for positive intervention.

Toward a science of translational science.

Translational research as a discipline has experienced explosive growth over the last decade as evidenced by significant federal investment and the exponential increase in related publications. However, narrow project-focused or process-based measurement approaches have resulted in insufficient techniques to measure the translational progress of institutions or large-scale networks. A shift from traditional industrial engineering approaches to systematic investigation using the techniques of scientometrics and network science will be required to assess the impact of investments in translational research.

Response of bone subjected to optimized high dose irradiation.

Allograft tissues are used in over one million musculoskeletal procedures per year. Consequently, it is crucial tissue banks use procedures to militate against allograft associated bacterial and viral infections. Recent studies have identified an important pathogen inactivation technology for musculoskeletal allografts that utilizes high-dose gamma irradiation (50 kGy) under controlled conditions. A total dose of 50 kGy assures that the current standard for medical devices for a microbial sterility assurance level of 10(- 6) is met. Furthermore, the pathogen inactivation technology results in a greater than four log inactivation of enveloped and nonenveloped viruses. Efficacious clinical outcome from musculoskeletal allografts exposed to this innovative sterilization procedure will require that there is no performance decrement in the allograft's biological properties. Therefore, to validate this objective, we executed a study focusing on remodeling and osteoconduction of bone allografts treated with a high dose of gamma irradiation (50 kGy), radioprotectants and well-defined operating parameters of temperature and water content. A rabbit calvarial model was used to test the hypothesis that remodeling and osteoconduction of allogeneic bone treated with the new pathogen inactivation technology would be equivalent to nontreated allogeneic bone. Results indicated treated bone allografts were comparable to nontreated allografts. We conclude, therefore, that based on this outcome and other reports, that high doses of gamma irradiation under optimized conditions designed to reduce free radical damage to tissue will provide safer allografts.

High-dose gamma irradiation for soft tissue allografts: High margin of safety with biomechanical integrity.

Screening and processing methods currently in place have made the risk of bacterial and viral infections from allograft tissues extremely low. However, the development of a terminal sterilization method that does not adversely affect tissue function would provide an added safety to tissues for transplantation. We assessed whether high-dose gamma irradiation could be used as an effective terminal sterilization method for allografts without impairing the preimplantation mechanical integrity of the tissues. Semitendinosus tendons were pretreated with a radioprotectant solution and then irradiated to 50 kGy under well-defined conditions that included a tight dose range and maintained low temperatures. Maximum force, strain, stress, modulus, and strain energy density for tendons irradiated to 50 kGy were compared to nonirradiated control tendons and tendons irradiated to 18 kGy by a commercial tissue bank using their existing method. The preimplantation biomechanical properties of the 50-kGy group compared favorably to the nonirradiated and 18 kGy groups. A study to evaluate the postimplantation mechanical and biological performance of grafts irradiated to 50 kGy is ongoing. Pathogen inactivation was also quantified following 50 kGy of irradiation, with > or =4.5 logs of Sindbis virus and 4.9 logs of parvovirus kill achieved. Analysis of Clostridium sordellii inactivation kinetics indicated that a 16 log10 reduction is predicted with 50 kGy of irradiation. A high dose of gamma irradiation using the described conditions can reduce infectious risks associated with soft tissue allografts while maintaining the preimplantation biomechanical performance of the tissues.

Effective use of optimized, high-dose (50 kGy) gamma irradiation for pathogen inactivation of human bone allografts.

The safety of tissue allografts has come under increased scrutiny due to recent reports of allograft-associated bacterial and viral infections in tissue recipients. We report that 50 kGy of gamma irradiation, nearly three times the dose currently used, is an effective pathogen inactivation method when used under optimized conditions that minimize damage to the tissue. Cancellous bone dowels treated with a radioprotectant solution and 50 kGy of optimized irradiation had an ultimate compressive strength and modulus of elasticity equal to conventionally irradiated (18 kGy) and non-irradiated control bone grafts. We subjected bone dowels treated with this pathogen inactivation method to an in vitro cytotoxicity test using three different mammalian cell lines and concluded that the treated grafts were not cytotoxic. The log reduction of nine pathogens spiked into radioprotectant-treated bone irradiated to 50 kGy was also tested. We achieved 4.9 logs of inactivation of a model virus for HIV and hepatitis C and 5 logs inactivation of a model virus for human parvovirus B-19. Complete inactivation (6.0-9.2 logs) of seven clinically relevant microorganisms was demonstrated. The results show that a combination of radioprotectants and optimized, high-dose gamma irradiation is a viable method for producing safer cancellous bone grafts that have the mechanical strength of existing grafts.

Effective use of gamma irradiation for pathogen inactivation of monoclonal antibody preparations.

Gamma irradiation has been used for decades as an effective method of pathogen inactivation of relatively inert materials. Until recently, its application to biologicals has resulted in unacceptable losses in functional activity. In this report we demonstrate that the damaging secondary effects of gamma irradiation can be controlled while maintaining the pathogen inactivation properties due to damage by primary effects. Control is achieved by a combination of protection from free radical damage to a monoclonal antibody through the use of the antioxidant ascorbate and by freeze-drying to minimize the potential for generating free radicals. The data demonstrate a synergy of these two approaches that results in quantitative recovery of functional activity while maintaining the ability to inactivate greater than 5 logs of porcine parvovirus infectivity.