Towards Personalized Prostate Cancer Therapy Using Delta-Reachability Analysis

Recent clinical studies suggest that the efficacy of hormone therapy for prostate cancer depends on the characteristics of individual patients. In this paper, we develop a computational framework for identifying patient-specific androgen ablation therapy schedules for postponing the potential cancer relapse. We model the population dynamics of heterogeneous prostate cancer cells in response to androgen suppression as a nonlinear hybrid automaton. We estimate personalized kinetic parameters to characterize patients and employ $\delta$-reachability analysis to predict patient-specific therapeutic strategies. The results show that our methods are promising and may lead to a prognostic tool for personalized cancer therapy.Comment: HSCC 201

A framework for automated conflict detection and resolution in medical guidelines

This research is supported by the MRC-funded UK Research and Innovation grant MR/S003819/1 and by EPSRC grant EP/M014290/1.Common chronic conditions are routinely treated following standardised procedures known as clinical guidelines. For patients suffering from two or more chronic conditions, known as multimorbidity, several guidelines have to be applied simultaneously, which may lead to severe adverse effects when the combined recommendations and prescribed medications are inconsistent or incomplete. This paper presents an automated formal framework to detect, highlight and resolve conflicts in the treatments used for patients with multimorbidities focusing on medications. The presented extended framework has a front-end which takes guidelines captured in a standard modelling language and returns the visualisation of the detected conflicts as well as suggested alternative treatments. Internally, the guidelines are transformed into formal models capturing the possible unfoldings of the guidelines. The back-end takes the formal models associated with multiple guidelines and checks their correctness with a theorem prover, and inherent inconsistencies with a constraint solver. Key to our approach is the use of an optimising constraint solver which enables us to search for the best solution that resolves/minimises conflicts according to medication efficacy and the degree of severity in case of harmful combinations, also taking into account their temporal overlapping. The approach is illustrated throughout with a real medical example.Publisher PDFPeer reviewe

Dimensional Consistency Analysis in Complex Algebraic Models

Relations in complex algebraic models include numerous variables and parameter that capture the physical dimensions of the objects represented in models (such as "mass", or "volume" of an object). A model developer must ensure the semantic correctness of the model, which includes consistency across physical dimensions and their units of measure in the model relations. Such dimensional consistency analysis is the subject of the research described in this paper. We propose a new methodological framework for this type of analysis which comprises: - a two-level structure for representing knowledge about physical dimensions and units of measure; and - the dimensional analysis algorithm that uses this structured knowledge for the verification of consistency. The proposed methodology allows us to resolve issues related to handling complex non-decomposable units of measure and the situation when instances of the same physical dimension are associated with different physical quantities. We illustrate the proposed methodological framework using mathematical relations from a comprehensive environmental model developed at IIASA

Dialogue games for explaining medication choices

SMT solvers can be used efficiently to search for optimal paths across multiple graphs when optimising for certain resources. In the medical context, these graphs can represent treatment plans for chronic conditions where the optimal paths across all plans under consideration are the ones which minimize adverse drug interactions. The SMT solvers, however, work as a black-box model and there is a need to justify the optimal plans in a human-friendly way. We aim to fulfill this need by proposing explanatory dialogue protocols based on computational argumentation to increase the understanding and trust of humans interacting with the system. The protocols provide supporting reasons for nodes in a path and also allow counter reasons for the nodes not in the graph, highlighting any potential adverse interactions during the dialogue.Postprin

Consistency checking of STNs with decisions: Managing temporal and access-control constraints in a seamless way

A Simple Temporal Network (STN) consists of time points modeling temporal events and constraints modeling the minimal and maximal temporal distance between them. A Simple Temporal Network with Decisions (STND) extends an STN to model temporal plans with decisions. STNDs label time points and constraints by conjunctions of literals saying for which scenarios (i.e., complete truth value assignments to the propositions) they are relevant. In this paper, we deal with the use of STNDs for modeling and synthesizing execution strategies. We propose an incremental hybrid SAT-based consistency checking algorithm for STNDs that is faster than the one previously proposed and allows for the synthesis of all consistent scenarios and related early execution schedules (offline temporal planning). We carry out an experimental evaluation with Kappa, a tool that we developed for STNDs. We also show that any STND can be easily translated into a disjunctive temporal network and vice versa