Better generalisation reduces the need for extensive and costly screens at single-cell resolution.

We perform a random search [43] for hyperparameter optimization over the search ranges in Table 6.

Prognostication for comatose post-cardiac arrest patients is a critical challenge that directly impacts clinical decision-making in the ICU. Clinical information that informs prognostication is collected serially over time. Shortly after cardiac arrest, various time-invariant baseline features are collected (e.g., demographics, cardiac arrest characteristics). After ICU admission, additional features are gathered, including time-varying hemodynamic data (e.g., blood pressure, doses of vasopressor medications). We view these as two phases in which we collect new features. In this study, we propose a novel stepwise dynamic competing risks model that improves the prediction of neurological outcomes by automatically determining when to take advantage of time-invariant features (first phase) and time-varying features (second phase). Notably, our model finds patients for whom this second phase (time-varying hemodynamic) information is beneficial for prognostication and also when this information is beneficial (as we collect more hemodynamic data for a patient over time, how important these data are for prognostication varies). Our approach extends the standard Fine and Gray model to explicitly model the two phases and to incorporate neural networks to flexibly capture complex nonlinear feature relationships. Evaluated on a retrospective cohort of 2,278 comatose post-arrest patients, our model demonstrates robust discriminative performance for the competing outcomes of awakening, withdrawal of life-sustaining therapy, and death despite maximal support. Our approach generalizes to more than two phases in which new features are collected and could be used in other dynamic prediction tasks, where it may be helpful to know when and for whom newly collected features significantly improve prediction.

Digital twins are models of real-world systems that can simulate their dynamics in response to potential actions. In complex settings, the state and action variables, and available data and knowledge relevant to a system can constantly change, requiring digital twins to continuously update with these changes to remain relevant. Current approaches struggle in this regard, as they require fixed, well-defined modelling environments, and they cannot adapt to novel variables without re-designs, or incorporate new information without re-training. To address this, we frame digital twinning as an in-context learning problem using large language models, enabling seamless updates to the twin at inference time. We develop CALM-DT, a Context-Adaptive Language Model-based Digital Twin that can accurately simulate across diverse state-action spaces using in-context learning alone by utilising fine-tuned encoders for sample retrieval. We empirically demonstrate CALM-DT's competitive performance with existing digital twin approaches, and its unique ability to adapt to changes in its modelling environment without parameter updates.

The COVID-19 pandemic has severely affected public health, healthcare systems, and daily life, especially amid resource shortages and limited workers. This crisis has underscored the urgent need for automation in hospital environments, particularly disinfection, which is crucial to controlling virus transmission and improving the safety of healthcare personnel and patients. Ultraviolet (UV) light disinfection, known for its high efficiency, has been widely adopted in hospital settings. However, most existing research focuses on maximizing UV coverage while paying little attention to the impact of human activity on virus distribution. To address this issue, we propose a mobile robotic system for UV disinfection focusing on the virus hotspot. The system prioritizes disinfection in high-risk areas and employs an approach for optimized UV dosage to ensure that all surfaces receive an adequate level of UV exposure while significantly reducing disinfection time. It not only improves disinfection efficiency but also minimizes unnecessary exposure in low-risk areas. In two representative hospital scenarios, our method achieves the same disinfection effectiveness while reducing disinfection time by 30.7% and 31.9%, respectively. The video of the experiment is available at: https://youtu.be/wHcWzOcoMPM.

A combinatorial intervention, consisting of multiple treatments applied to a single unit with potentially interactive effects, has substantial applications in fields such as biomedicine, engineering, and beyond. Given $p$ possible treatments, conducting all possible $2^p$ combinatorial interventions can be laborious and quickly becomes infeasible as $p$ increases. Here we introduce probabilistic factorial experimental design, formalized from how scientists perform lab experiments. In this framework, the experimenter selects a dosage for each possible treatment and applies it to a group of units. Each unit independently receives a random combination of treatments, sampled from a product Bernoulli distribution determined by the dosages. Additionally, the experimenter can carry out such experiments over multiple rounds, adapting the design in an active manner. We address the optimal experimental design problem within an intervention model that imposes bounded-degree interactions between treatments. In the passive setting, we provide a closed-form solution for the near-optimal design. Our results prove that a dosage of $\tfrac{1}{2}$ for each treatment is optimal up to a factor of $1+O(\tfrac{\ln(n)}{n})$ for estimating any $k$-way interaction model, regardless of $k$, and imply that $O\big(kp^{3k}\ln(p)\big)$ observations are required to accurately estimate this model. For the multi-round setting, we provide a near-optimal acquisition function that can be numerically optimized. We also explore several extensions of the design problem and finally validate our findings through simulations.

Learning the response of single-cells to various treatments offers great potential to enable targeted therapies. In this context, neural optimal transport (OT) has emerged as a principled methodological framework because it inherently accommodates the challenges of unpaired data induced by cell destruction during data acquisition. However, most existing OT approaches are incapable of conditioning on different treatment contexts (e.g., time, drug treatment, drug dosage, or cell type) and we still lack methods that unanimously show promising generalization performance to unseen treatments. Here, we propose the Conditional Monge Gap which learns OT maps conditionally on arbitrary covariates. We demonstrate its value in predicting single-cell perturbation responses conditional to one or multiple drugs, a drug dosage, or combinations thereof. We find that our conditional models achieve results comparable and sometimes even superior to the condition-specific state-of-the-art on scRNA-seq as well as multiplexed protein imaging data. Notably, by aggregating data across conditions we perform cross-task learning which unlocks remarkable generalization abilities to unseen drugs or drug dosages, widely outperforming other conditional models in capturing heterogeneity (i.e., higher moments) in the perturbed population. Finally, by scaling to hundreds of conditions and testing on unseen drugs, we narrow the gap between structure-based and effect-based drug representations, suggesting a promising path to the successful prediction of perturbation effects for unseen treatments.