Claire M. Miller | Searcharxiv

arXiv2025

In silico trials of acute ischemic stroke: predicting the total potential for improvement to patient functional outcomes

This study uses in silico trials (ISTs) to quantify the potential for benefit due to improved recanalisation outcomes and shorter time to treatment for acute ischaemic stroke (AIS) patients. We use an IST framework to run trials on cohorts of virtual patients with early and late treatment after stroke onset, and with successful (full) and unsuccessful (no) recanalisation outcomes. Using a virtual population of AIS patients, and in silico models of blood flow, perfusion, and tissue death, we predict the functional independence of each patient at 90 days using the modified Rankin Scale (mRS). Results predict 57% of the virtual population achieve functional independence with full recanalisation and a treatment time of 4 hours or less, compared to 29% with no recanalisation and more than 4 hours to treatment. Successful recanalisation was more beneficial than faster treatment: the best-case common odds ratio (improved mRS) due to recanalisation was 2.7 compared to 1.6 for early treatment. This study provides a proof-of-concept for a novel use-case of ISTs: quantifying the maximum potential for improvement to patient outcomes. This would be useful during early stages of therapy development, to determine the target populations and therapy goal with the greatest potential for population improvements.

q-bio.TO↗

arXiv2025

Sunlight-heated refugia protect frogs from chytridiomycosis: a mathematical modelling study

The fungal disease Chytridiomycosis poses a threat to frog populations worldwide. It has driven over 90 amphibian species to extinction and severely affected hundreds more. Difficulties in disease management have shown a need for novel conservation approaches. We present a novel mathematical model for chytridiomycosis transmission in frogs that includes the natural history of infection, to test the hypothesis that sunlight-heated refugia reduce transmission. The model is fit using approximate Bayesian computation to experimental data where a cohort of frogs, a fixed subset of which had cleared a prior infection, were provided access to either sunlight-heated or shaded refugia. Using our model, we can estimate the extent to which prior chytridiomycosis infection protects against subsequent infection, and quantify the effect of sunlight-heating of refugia. Results estimate a 40% reduction in chytridiomycosis transmission when frogs have access to sunlight-heated refugia, compared to shaded refugia. This strongly supports the hypothesis that the sunlight-heated refugia reduce disease transmission. Frogs that were infected and recovered were estimated to have a reduction in susceptibility of approximately 97% compared to frogs with no prior infection. This research provides quantitative evidence supporting sunlight-heated refugia as an effective disease management tool for chytridiomycosis in frog populations. By estimating both the impact of refugia and the protective effects of prior infection, the model provides an evidence base for implementing sunlight-heated refugia as part of amphibian conservation strategies. This work represents an important first step in using mathematical modelling to inform policy on the design and implementation of habitat-based interventions to support amphibian population recovery and long-term sustainability.

q-bio.PE↗