Multi-scale mechanistic modelling of the host defence in invasive aspergillosis reveals leucocyte activation and iron acquisition as drivers of infection outcome.

Aspergillus species are ubiquitous environmental moulds, with spores inhaled daily by most humans. Immunocompromised hosts can develop an invasive infection resulting in high mortality. There is, therefore, a pressing need for host-centric therapeutics for this infection. To address it, we created a multi-scale computational model of the infection, focused on its interaction with the innate immune system and iron, a critical nutrient for the pathogen. The model, parameterized using published data, was found to recapitulate a wide range of biological features and was experimentally validated in vivo. Conidial swelling was identified as critical in fungal strains with high growth, whereas the siderophore secretion rate seems to be an essential prerequisite for the establishment of the infection in low-growth strains. In immunocompetent hosts, high growth, high swelling probability and impaired leucocyte activation lead to a high conidial germination rate. Similarly, in neutropenic hosts, high fungal growth was achieved through synergy between high growth rate, high swelling probability, slow leucocyte activation and high siderophore secretion. In summary, the model reveals a small set of parameters related to fungal growth, iron acquisition and leucocyte activation as critical determinants of the fate of the infection.

Internet-based hoarding assessment: The reliability and predictive validity of the internet-based Hoarding Rating Scale, Self-Report.

The Hoarding Rating Scale, Self Report (HRS-SR) is a 5-item assessment developed to ascertain the presence and severity of hoarding symptoms. This study aimed to evaluate the validity of an online adaptation of the HRS-SR in a remote, unsupervised internet sample of 23,214 members of the Brain Health Registry (BHR), an online research registry that evaluates and longitudinally monitors cognition, medical and psychiatric health status. Convergent validity was assessed among a sub-sample of 1,183 participants who completed additional, remote measures of self-reported hoarding behaviors. Structured clinical interviews conducted in-clinic and via video conferencing tools were conducted among 230 BHR participants; ROC curves were plotted to assess the diagnostic performance of the internet-based HRS-SR using best estimate hoarding disorder (HD) diagnoses as the gold standard. The area under the curve indicated near-perfect model accuracy, and was confirmed with 10-fold cross validation. Sensitivity and specificity for distinguishing clinically relevant hoarding were optimized using an HRS-SR total score cut-off of 5. Longitudinal analyses indicated stability of HRS-SR scores over time. Findings indicate that the internet-based HRS-SR is a useful and valid assessment of hoarding symptoms, though additional research using samples with more diverse hoarding behavior is needed to validate optimal cut-off values.