Parameter Identifiability in PDE Models of Fluorescence Recovery After Photobleaching.

Identifying unique parameters for mathematical models describing biological data can be challenging and often impossible. Parameter identifiability for partial differential equations models in cell biology is especially difficult given that many established in vivo measurements of protein dynamics average out the spatial dimensions. Here, we are motivated by recent experiments on the binding dynamics of the RNA-binding protein PTBP3 in RNP granules of frog oocytes based on fluorescence recovery after photobleaching (FRAP) measurements. FRAP is a widely-used experimental technique for probing protein dynamics in living cells, and is often modeled using simple reaction-diffusion models of the protein dynamics. We show that current methods of structural and practical parameter identifiability provide limited insights into identifiability of kinetic parameters for these PDE models and spatially-averaged FRAP data. We thus propose a pipeline for assessing parameter identifiability and for learning parameter combinations based on re-parametrization and profile likelihoods analysis. We show that this method is able to recover parameter combinations for synthetic FRAP datasets and investigate its application to real experimental data.

Barriers and facilitators to scaling up access to HIV pre-exposure prophylaxis among key populations: A qualitative study of the incentive-based PrEP Seguro program in Mexico.

Introduction: Daily oral pre-exposure prophylaxis (PrEP) is highly safe and effective for HIV prevention, yet barriers to PrEP access and adherence persist among key populations. In Mexico, incentive-based pilot programs have been effective in improving PrEP adherence among male sex workers. Understanding the experiences of providers and program implementers is critical to integrating PrEP adherence programs as part of standard care in Mexico and similar settings. Methods: We conducted 17 in-depth informational interviews with care providers and staff responsible for administering PrEP to key populations (men who have sex with men, male sex workers, transgender women) in Mexico City. Interviews explored successes and challenges surrounding current PrEP implementation, as well as adaptations that could facilitate national scale-up of PrEP programs in Mexico. Informant transcripts were analyzed using a hybrid inductive-deductive thematic analysis approach utilizing CFIR constructs for the initial codebook while allowing for inductive findings. Results: Three key themes emerged from informant interviews as important for promoting PrEP programs in Mexico: 1) increasing individual PrEP access, 2) strengthening quality of care, and 3) improving organizational and structural support. Conclusions: PrEP in Mexico is currently only available in a few clinics with high patient populations, and siloed HIV services, stigma, and a lack of inter-organizational collaboration remain persistent barriers to PrEP uptake. Promoting government collaboration and increasing financial support for community-based organizations is needed to expand PrEP access. Tailored, destigmatizing information about PrEP services needs to be diffused among both staff and patients to strengthen care quality.