A systematic review of simulation methods applied to cancer care services.

There is significant potential for Operational Research to support improvements in care services for cancer patients. In this systematic review, we examine computer simulation techniques used in supporting hospital-based cancer care, the type of problems addressed, the quality of the model and implementation, and the impact on patients. We identified 51 papers distributed between four problem types: patient flow/pathway modelling, scheduling, cost analysis, and resource allocation.

Exploring the role of mass immunisation in influenza pandemic preparedness: A modelling study for the UK context.

The nature and timing of the next influenza pandemic is unknown. This makes it difficult for policy makers to assess whether spending money now to prepare for mass immunisation in the event of a pandemic is worthwhile. We used simple epidemiological modelling and health economic analysis to identify the range of pandemic and policy scenarios under which plans to immunise the general UK population would have net benefit if a stockpiled vaccine or, alternatively, a responsively purchased vaccine were used.

Operational analysis of school-based delivery models to vaccinate children against influenza.

Large-scale immunisation programmes against seasonal influenza are characterised by logistical challenges related to the need for vaccinating large cohorts of people in a short amount of time. Careful operational planning of resources is essential for a successful implementation of such programmes. We focused on the process of child vaccination in schools and analysed the staffing and workflow aspects of a school-aged children vaccination programme in England.

A method for evaluating the cost-benefit of different preparedness planning policies against pandemic influenza.

•Our work presents a unifying method to calculate the net-benefit of different preparedness policies against different pandemic influeunza strains. Unlike previous methods, which have focused on evaluating specific strategies against specific pandemics, our method allows assessment of mass immunisation strategies in presence and absence of antiviral drugs for a large range of pandemic influenza strain characteristics and programme features. Overall, the model described here combines two parts to evaluate different preparedness planning policies against pandemic influenza.

A tool for routine monitoring and feedback of morbidities following paediatric cardiac surgery.

Short-term survival after paediatric cardiac surgery has improved significantly over the past 20 years and increasing attention is being given to measuring and reducing incidence of morbidities following surgery. How to best use routinely collected data to share morbidity information constitutes a challenge for clinical teams interested in analysing their outcomes for quality improvement. We aimed to develop a tool facilitating this process in the context of monitoring morbidities following paediatric cardiac surgery, as part of a prospective multi-centre research study in the United Kingdom.

Are we prepared for the next influenza pandemic? Lessons from modelling different preparedness policies against four pandemic scenarios.

In the event of a novel influenza strain that is markedly different to the current strains circulating in humans, the population have little/no immunity and infection spreads quickly causing a global pandemic. Over the past century, there have been four major influenza pandemics: the 1918 pandemic ("Spanish Flu"), the 1957-58 pandemic (the "Asian Flu"), the 1967-68 pandemic (the "Hong Kong Flu") and the 2009 pandemic (the "Swine flu"). To inform planning against future pandemics, this paper investigates how different is the net-present value of employing pre-purchase and responsive- purchased vaccine programmes in presence and absence of anti-viral drugs to scenarios that resemble these historic influenza pandemics.

Informing decisions on the purchase of equipment used by health services in response to incidents involving hazardous materials.

Accidents involving release of chemical, biological, radiological or nuclear substances may prompt the need to decontaminate exposed casualties prior to further medical treatment. Health service workers who carry out decontamination procedures wear protective suits to avoid direct contact with contaminants. We developed an analytical framework based on queueing theory to inform UK Department of Health's decisions on the stock of protective suits that ambulance services and hospitals with emergency departments in England should hold.

The shortest path is not the one you know: application of biological network resources in precision oncology research.

Several decades of molecular biology research have delivered a wealth of detailed descriptions of molecular interactions in normal and tumour cells. This knowledge has been functionally organised and assembled into dedicated biological pathway resources that serve as an invaluable tool, not only for structuring the information about molecular interactions but also for making it available for biological, clinical and computational studies. With the advent of high-throughput molecular profiling of tumours, close to complete molecular catalogues of mutations, gene expression and epigenetic modifications are available and require adequate interpretation.

Independent component analysis uncovers the landscape of the bladder tumor transcriptome and reveals insights into luminal and basal subtypes.

Extracting relevant information from large-scale data offers unprecedented opportunities in cancerology. We applied independent component analysis (ICA) to bladder cancer transcriptome data sets and interpreted the components using gene enrichment analysis and tumor-associated molecular, clinicopathological, and processing information. We identified components associated with biological processes of tumor cells or the tumor microenvironment, and other components revealed technical biases.

Computational modeling of the main signaling pathways involved in mast cell activation.

A global and rigorous understanding of the signaling pathways and cross-regulatory processes involved in mast cell activation requires the integration of published information with novel functional datasets into a comprehensive computational model. Based on an exhaustive curation of the existing literature and using the software CellDesigner, we have built and annotated a comprehensive molecular map for the FcεRI signaling network. This map can be used to visualize and interpret high-throughput expression data.

[Biological network modelling and precision medicine in oncology].

Precision medicine in oncology is becoming reality thanks to the next-generation sequencing of tumours and the development of targeted inhibitors enabling tailored therapies. Many clinical trials base their strategy on the identification of mutations to deliver the targeted inhibitor that counteract supposedly the effect of a mutated gene. Recent results have shown that this gene-centered strategy can be successful, but can also fall short in stopping progression.

Integrative modelling of the influence of MAPK network on cancer cell fate decision.

The Mitogen-Activated Protein Kinase (MAPK) network consists of tightly interconnected signalling pathways involved in diverse cellular processes, such as cell cycle, survival, apoptosis and differentiation. Although several studies reported the involvement of these signalling cascades in cancer deregulations, the precise mechanisms underlying their influence on the balance between cell proliferation and cell death (cell fate decision) in pathological circumstances remain elusive. Based on an extensive analysis of published data, we have built a comprehensive and generic reaction map for the MAPK signalling network, using CellDesigner software.

Proteomic analysis of the SH2 domain-containing leukocyte protein of 76 kDa (SLP76) interactome in resting and activated primary mast cells [corrected].

We report the first proteomic analysis of the SLP76 interactome in resting and activated primary mouse mast cells. This was made possible by a novel genetic approach used for the first time here. It consists in generating knock-in mice that express signaling molecules bearing a C-terminal tag that has a high affinity for a streptavidin analog.

Comparison of immunological characteristics of peripheral, splenic and tonsilar naïve B cells by differential gene expression meta-analyses.

Background: Naïve B cells isolated from peripheral blood, spleen and tonsil are commonly used in human B cell studies. However, little has been written about their possible variations in immunological properties. This study compared differential gene expression in human naive B subsets by meta-analysis using expression data available in Gene Expression Onimbus (GEO).