On-lattice agent-based simulation of populations of cells within the open-source chaste framework

Over the years, agent-based models have been developed that combine cell division and reinforced random walks of cells on a regular lattice, reaction-diffusion equations for nutrients and growth factors and ordinary differential equations (ODEs) for the subcellular networks regulating the cell cycle. When linked to a vascular layer, this multiple scale model framework has been applied to tumour growth and therapy. Here we report on the creation of an agent-based multiscale environment amalgamating the characteristics of these models within a Virtual Pysiological Human (VPH) Exemplar Project. This project enables re-use, integration, expansion and sharing of the model and relevant data. The agent-based and reactiondiffusion parts of the multiscale model have been implemented and are available for download as part of the latest public release of Chaste (“Cancer, Heart and Soft Tissue Environment”), (http://www.cs.ox.ac.uk/chaste/) version 3.1, part of the VPH Toolkit (http://toolkit.vph-noe.eu/). The environment functionalities are verified against the original models, in addition to extra validation of all aspects of the code. In this work, we present the details of the implementation of the agent-based environment, including the system description, the conceptual model, the development of the simulation model and the processes of verification and validation of the simulation results. We explore the potential use of the environment by presenting exemplar applications of the “what if” scenarios that can easily be studied in the environment. These examples relate to tumour growth, cellular competition for resources and tumour responses to hypoxia. We conclude our work by summarising the future steps for the expansion of the current system

The ALICE electromagnetic calorimeter high level triggers

The ALICE (A Large Ion Collider Experiment) detector yields a huge sample of data from different sub-detectors. On-line data processing is applied to select and reduce the volume of the stored data. ALICE applies a multi-level hardware trigger scheme where fast detectors are used to feed a three-level (L0, L1, and L2) deep chain. The High-Level Trigger (HLT) is a fourth filtering stage sitting logically between the L2 trigger and the data acquisition event building. The EMCal detector comprises a large area electromagnetic calorimeter that extends the momentum measurement of photons and neutral mesons up to $p_T=250$ GeV/c, which improves the ALICE capability to perform jet reconstruction with measurement of the neutral energy component of jets. An online reconstruction and trigger chain has been developed within the HLT framework to sharpen the EMCal hardware triggers, by combining the central barrel tracking information with the shower reconstruction (clusters) in the calorimeter. In the present report the status and the functionality of the software components developed for the EMCal HLT online reconstruction and trigger chain will be discussed, as well as preliminary results from their commissioning performed during the 2011 LHC running period.Comment: Proceeding for the CHEP 2012 Conferenc

The time has come for physicians to take notice: the impact of psychosocial stressors on the heart.

A rapidly growing body of evidence supports a relationship between psychosocial factors and cardiovascular disease. In this article, a review of the epidemiologic and clinical research investigating this relationship concludes that psychosocial stressors can be both a cause and a consequence of cardiovascular disease events. Furthermore, recent data have shown that stress management might reduce future cardiac events in patients with cardiovascular disease. Unfortunately, the influence of psychosocial risk factors on cardiovascular disease remains underrecognized compared with traditional cardiac risk factors. Physicians and their associates should screen for psychosocial stressors and recognize potential symptoms. Consideration should be given to developing improved liaison relationships with psychologic or behavioral specialists to facilitate more specialized interventions when appropriate. A variety of interventions conducted by appropriately trained mental health professionals have successfully improved stress in patients with cardiovascular disease and other chronic diseases. The time has come for physicians to recognize the impact of psychosocial stressors on cardiovascular disease

A Review of Neurogenic Stunned Myocardium.

Neurologic stunned myocardium (NSM) is a phenomenon where neurologic events give rise to cardiac abnormalities. Neurologic events like stroke and seizures cause sympathetic storm and autonomic dysregulation that result in myocardial injury. The clinical presentation can involve troponin elevation, left ventricular dysfunction, and ECG changes. These findings are similar to Takotsubo cardiomyopathy and acute coronary syndrome. It is difficult to distinguish NSM from acute coronary syndrome based on clinical presentation alone. Because of this difficulty, a patient with NSM who is at high risk for coronary heart disease may undergo cardiac catheterization to rule out coronary artery disease. The objective of this review of literature is to enhance physician\u27s awareness of NSM and its features to help tailor management according to the patient\u27s clinical profile

Alcoholic cardiomyopathy: a review.

Alcohol abuse can cause cardiomyopathy indistinguishable from other types of dilated nonischemic cardiomyopathy. Most heavy drinkers remain asymptomatic in the earlier stages of disease progression, and many never develop the familiar clinical manifestations that typify heart failure. We review the current thinking on the pathophysiology, clinical characteristics, and treatments available for alcoholic cardiomyopathy. The relationship of alcohol to heart disease is complicated by the fact that in moderation, alcohol has been shown to afford a certain degree of protection against cardiovascular disease

Controversies in the management of the renal artery stenosis

Optimal management of renal artery stenosis has continued to remain elusive. The previous non randomized studies and registry data suggested a benefit of renal artery stenting. However, the recently completed randomized studies comparing renal stenting to medical management failed to show any benefit. These studies had some flaws in their design and methodology. In an appropriately selected patient population renal artery stenting may have a role. In addition, there might be some role of adjunctive therapies like antiplatelet medications and embolic protection. This review summarizes the current literature on this controversial topic

Low-density lipoprotein cholesterol lowering therapies: what is on the horizon?

Elevated low-density lipoprotein cholesterol (LDL-C) levels are associated with an increased risk for cardiovascular disease (CVD). Statins have been the cornerstone of lipid therapy to lower LDL-C for the past two decades, but despite significant clinical efficacy in a majority of patients, a large residual risk remains for the development of initial or recurrent atherosclerotic CVD. In addition, owing to the side-effects, a significant percentage of patients cannot tolerate any statin dose or a high enough statin dose. Thus, novel therapeutic agents are currently being developed to lower LDL-C levels further. This review will highlight these novel therapeutic agents including antisense oligonucleotides focused on apolipoprotein B, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and microsomal triglyceride transfer protein inhibitors. For each therapeutic class, an overview of mechanism of action, pharmacokinetic data, and efficacy/safety evidence will be discussed

Alcohol and arrhythmias: a comprehensive review.

The use of alcohol as a social lubricant has been ubiquitous in human societies since ancient times. It has also long been recognized that alcohol produces undesirable cardiovascular effects, especially when imbibed in excess. Numerous investigators have noted a causal relationship between alcohol and arrhythmias, as well as sudden cardiac death. We have undertaken a comprehensive review of the literature on alcohol as a potential trigger for arrhythmias. We have reviewed the major epidemiological studies undertaken on this subject. We have also explored pathophysiological mechanisms that drive the arrythmogenic effects of alcohol. In conclusion, although there is definite proof in the literature to implicate alcohol as a culprit in arrhythmias, the relationship is complex

Tachycardia mediated cardiomyopathy: pathophysiology, mechanisms, clinical features and management.

Tachycardia mediated cardiomyopathy (TMC) is a reversible form of dilated cardiomyopathy that can occur with most supraventricular and ventricular arrhythmias. Despite the plethora of literature describing this entity in animal models, as well as humans, it remains poorly understood. Over the last decade, new etiologies of TMC, such as frequent premature ventricular complexes in normal hearts, have been identified. Recent advances in catheter-based ablation therapies, particularly for atrial fibrillation and ventricular arrhythmias, have added a new dimension to the treatment of this condition. This review describes the pathophysiology, proposed mechanisms, clinical features and management in various arrhythmic conditions