Oncology

Increasingly many scientific questions, that need modelling solutions, target processes residing on multiple scale levels. This is especially true in the domain of biomedicine, where understanding a given disease, or the effects of a treatment might involve numerous components. For a single problem blood flow mechanics can be just as important as cellular trafficking or sub-cellular biochemical signalling. One such problem presents itself with the disease of brain aneurysms. These are focal dilatations on major brain arteries with a chance to burst. The outcome of a rupture event can be devastating for the patient. The treatment usually involves endovascular brain surgery and the placement of a blood flow diverter implant, with the intent to thrombose the dilatation and therefore to close it out from the active circulation. In the following, a multiscale, multicomponent model will be presented that aims to model aspects of the thrombus formation mechanism after the medical intervention. The sub-models are fully developed and operational, and the couplings are currently under development. The model structure is discussed from the viewpoint of inter-model communication and requirements for the execution environment for the model components. Full Abstract

Hypothermia is known to impact multiple physiological mechanisms that include neurologic and cardiovascular systems. Therapeutic hypothermia (TH), as a mild reduction of body core temperature, has become the standard cardioprotective treatment for several patient groups, including those affected by ischemia. Patients undergoing long term treatments such as dialysis experience global ischemia in addition to the presence of localized myocardial stunning [1], which together may promote persistent ventricular fibrillation. Fibrillation avoidance or reduction of initiation risk using non-pharmacological TH may be beneficial to critically ill patients.
Basic science experimental studies have shown that hypothermia prolongs cardiomyocyte action potential [2] and reduces cardiac conduction velocity. However, the clinical effectiveness of TH on arrythmia abrogation remain debated. In this study, a multi-scale computational cardiology approach was used to illuminate the effects of TH on cardiomyocytes and tissue. Full Abstract

Acute myocardial ischemia is a major cause of sudden cardiac death. Anti-arrhythmic treatments or side-effects associated with cancer therapies can produce cardiotoxic effects increasing the occurrence of adverse cardiac events especially in patients with coronary artery disease. In-vivo and in-vitro drug trials have associated complications regarding ethics and costs, whereas cardiotoxic evaluation in animal experiments is not necessarily translatable to humans. Full Abstract

Human sinoatrial node (SAN) structure-function relationships remain poorly understood, and may be drastically dierent from those in smaller mammals. Recent studies based on histology for structure and optical mapping for function (e.g. see [1]) suggest that the human SAN may be electrically insulated from atrial tissue by an insulating border, except at four discrete exit pathways (SEPs) that permit atrial excitation by the SAN. Experimental data suggests that the funny current density is three fold lower in the human SAN as compared to small animals. The lower density of this important pacemaking ion channel may lead to SAN electrical activity suppression by the physiological atrial load in the absence of substantial SAN electrical insulation. In addition to experimental evidence, a recent computer modelling study provided some insights into the human SAN electrical function [2]. However, previous studies used simplied Fenton-Karma ionic model to simulate SAN activity, while a biophysically and anatomically detailed modelling has yet to be used to investigate the role of SEPs and human SAN behavior. In this study, a multi-scale biophysically detailed model of the human SAN is presented. The model is being used to investigate the role of SEPs, as well as relevant clinical conditions that promote bradycardia and brady-tachycardia. Full Abstract

Cancer results from modifications to cellular decision-making processes. In normal cells, the protein-mediated signaling networks that control growth and movement are tightly regulated. However, mutations that disrupt or over-activate signaling proteins can drive uncontrolled cell growth resulting in cancer. RAS, a peripheral membrane signaling protein, is mutated in 30% of all cancers, especially those of the pancreas, colon and lung. These oncogenic mutations result in the loss of GTPase activity which in turn causes persistent engagement of effectors and enhanced or continuous growth signaling. Full Abstract

Information extraction, integration, analytics and visualization is a critical need for the Precision Medicine Initiative aimed to accelerate our understanding of individual differences in people’s genes, environment, and lifestyle and their effect on disease prevention, progression, treatment, and survival. This data-intensive challenge is collecting, integrating, and analyzing massive, multi-source, multi-scale heterogeneous patient data that must be interpreted in the context of other highly relevant but disparate data sources such as socioeconomic, environmental, lifestyle, care delivery, and community infrastructure factors (i.e., “exposome”). Full Abstract

TWe live in the information age where the flow of knowledge, including medical advice and innovations, quickly reaches each of us. However, existing recommendations for disease prevention, diagnostics and treatment are population-based, or based on highly selected randomized controlled trials, and only seldomly account for individual differences. For effective control of globally increasing morbidity and mortality due to cancer, the focus on early detection and intervention cannot be underestimated. The estimated spiraling costs of cancer treatment will challenge even the highest-income countries and underline the urgent need to develop preventive efforts.
Knowledge of biological disease mechanisms along with existing individual data from national population-based health registries, biobanks and surveys can be tailored for personally designed ctions safely, efficiently and quickly.
Cervical cancer screening is an excellent model system for the development of personalised strategies for cancer prevention. It has a proven strong effect for decreasing cancer burden at the population level, and the Norwegian population-based screening program has produced large amounts of individual data that is accessible by centrally organized nationwide registries. Full Abstract