Meta-analysis of material properties influencing nanoparticle plasma pharmacokinetics.

Thorough characterization of the plasma pharmacokinetics (PK) is a critical step in clinical development of novel therapeutics and is routinely performed for small molecules and biologics. However, there is a paucity of even basic characterization of PK for nanoparticle-based drug delivery systems. This has led to untested generalizations about how nanoparticle properties govern PK. Here, we present a meta-analysis of 100 nanoparticle formulations following IV administration in mice to identify any correlations between four PK parameters derived by non-compartmental analysis (NCA) and four cardinal properties of nanoparticles: PEGylation, zeta potential, size, and material. There was a statistically significant difference between the PK of particles stratified by nanoparticle properties. However, single linear regression between these properties and PK parameters showed poor predictability (r2 < 0.10 for all analyses), while multivariate regressions showed improved predictability (r2 > 0.38, except for t1/2). This suggests that no single nanoparticle property alone is even moderately predictive of PK, while the combination of multiple nanoparticle features does provide moderate predictive power. Improved reporting of nanoparticle properties will enable more accurate comparison between nanoformulations and will enhance our ability to predict in vivo behavior and design optimal nanoparticles.

The Virtual Summer Research Program: supporting future physician-scientists from underrepresented backgrounds.

Introduction: Physician-scientist training programs expect applicants to have had extensive research experience prior to applying. Even at the best of times, this leaves individuals from underserved and underrepresented backgrounds at a competitive disadvantage, especially those remote from major academic centers. The COVID-19 pandemic exacerbated that disadvantage by closing research laboratories and suspending summer research opportunities. Methods: The Virtual Summer Research Program (VSRP) was designed to combat this shortfall by helping participating students become better informed and better prepared for applying to MD/DO-PhD programs. 156 participants were recruited from historically black colleges and universities and from national organizations for underrepresented trainees. Participants were paired with medical school faculty members and current MD/DO-PhD students from 35 participating institutions. The program lasted for at least 4 weeks and included a short research project, interactive sessions, journal clubs, social events, and attendance at a regional American Physician Scientists Association conference. Results: In follow-up surveys, participants reported improvements in their science-related skills and in their confidence in becoming a physician-scientist, applying to training programs, and navigating mentorship relationships. A follow-up study completed one year later indicated that participants felt they had benefited from an enhanced skill set, long-term relationships with their mentors, and connections to the physician-scientist community at large. Discussion: The results suggest that VSRP met its primary goals, which were to provide a diverse group of trainees with mentors, provide skills and resources for MD/DO-PhD application and matriculation and to support the development of longitudinal relationships between VSRP mentees and APSA. VSRP provides an approach that can be applied at an even larger scale when the constraints caused by a global pandemic have lifted.

Contact Tracing Apps: Lessons Learned on Privacy, Autonomy, and the Need for Detailed and Thoughtful Implementation.

The global and national response to the COVID-19 pandemic has been inadequate due to a collective lack of preparation and a shortage of available tools for responding to a large-scale pandemic. By applying lessons learned to create better preventative methods and speedier interventions, the harm of a future pandemic may be dramatically reduced. One potential measure is the widespread use of contact tracing apps. While such apps were designed to combat the COVID-19 pandemic, the time scale in which these apps were deployed proved a significant barrier to efficacy. Many companies and governments sprinted to deploy contact tracing apps that were not properly vetted for performance, privacy, or security issues. The hasty development of incomplete contact tracing apps undermined public trust and negatively influenced perceptions of app efficacy. As a result, many of these apps had poor voluntary public uptake, which greatly decreased the apps' efficacy. Now, with lessons learned from this pandemic, groups can better design and test apps in preparation for the future. In this viewpoint, we outline common strategies employed for contact tracing apps, detail the successes and shortcomings of several prominent apps, and describe lessons learned that may be used to shape effective contact tracing apps for the present and future. Future app designers can keep these lessons in mind to create a version that is suitable for their local culture, especially with regard to local attitudes toward privacy-utility tradeoffs during public health crises.