Clinical decision support system for point of care use--ontology-driven design and software implementation

OBJECTIVES: The objective of this research was to design a clinical decision support system (CDSS) that supports heterogeneous clinical decision problems and runs on multiple computing platforms. Meeting this objective required a novel design to create an extendable and easy to maintain clinical CDSS for point of care support. The proposed solution was evaluated in a proof of concept implementation. METHODS: Based on our earlier research with the design of a mobile CDSS for emergency triage we used ontology-driven design to represent essential components of a CDSS. Models of clinical decision problems were derived from the ontology and they were processed into executable applications during runtime. This allowed scaling applications' functionality to the capabilities of computing platforms. A prototype of the system was implemented using the extended client-server architecture and Web services to distribute the functions of the system and to make it operational in limited connectivity conditions. RESULTS: The proposed design provided a common framework that facilitated development of diversified clinical applications running seamlessly on a variety of computing platforms. It was prototyped for two clinical decision problems and settings (triage of acute pain in the emergency department and postoperative management of radical prostatectomy on the hospital ward) and implemented on two computing platforms--desktop and handheld computers. CONCLUSIONS: The requirement of the CDSS heterogeneity was satisfied with ontology-driven design. Processing of application models described with the help of ontological models allowed having a complex system running on multiple computing platforms with different capabilities. Finally, separation of models and runtime components contributed to improved extensibility and maintainability of the system

From Wearable Sensors to Smart Implants – Towards Pervasive and Personalised Healthcare

<p>Objective: This article discusses the evolution of pervasive healthcare from its inception for activity recognition using wearable sensors to the future of sensing implant deployment and data processing. Methods: We provide an overview of some of the past milestones and recent developments, categorised into different generations of pervasive sensing applications for health monitoring. This is followed by a review on recent technological advances that have allowed unobtrusive continuous sensing combined with diverse technologies to reshape the clinical workflow for both acute and chronic disease management. We discuss the opportunities of pervasive health monitoring through data linkages with other health informatics systems including the mining of health records, clinical trial databases, multi-omics data integration and social media. Conclusion: Technical advances have supported the evolution of the pervasive health paradigm towards preventative, predictive, personalised and participatory medicine. Significance: The sensing technologies discussed in this paper and their future evolution will play a key role in realising the goal of sustainable healthcare systems.</p> <p> </p

Grid-based semantic integration of heterogeneous data resources: Implementation on a HealthGrid

This thesis was submitted for the degree of Doctor of Philosophy and was awarded by Brunel University.The semantic integration of geographically distributed and heterogeneous data resources still remains a key challenge in Grid infrastructures. Today's mainstream Grid technologies hold the promise to meet this challenge in a systematic manner, making data applications more scalable and manageable. The thesis conducts a thorough investigation of the problem, the state of the art, and the related technologies, and proposes an Architecture for Semantic Integration of Data Sources (ASIDS) addressing the semantic heterogeneity issue. It defines a simple mechanism for the interoperability of heterogeneous data sources in order to extract or discover information regardless of their different semantics. The constituent technologies of this architecture include Globus Toolkit (GT4) and OGSA-DAI (Open Grid Service Architecture Data Integration and Access) alongside other web services technologies such as XML (Extensive Markup Language). To show this, the ASIDS architecture was implemented and tested in a realistic setting by building an exemplar application prototype on a HealthGrid (pilot implementation). The study followed an empirical research methodology and was informed by extensive literature surveys and a critical analysis of the relevant technologies and their synergies. The two literature reviews, together with the analysis of the technology background, have provided a good overview of the current Grid and HealthGrid landscape, produced some valuable taxonomies, explored new paths by integrating technologies, and more importantly illuminated the problem and guided the research process towards a promising solution. Yet the primary contribution of this research is an approach that uses contemporary Grid technologies for integrating heterogeneous data resources that have semantically different. data fields (attributes). It has been practically demonstrated (using a prototype HealthGrid) that discovery in semantically integrated distributed data sources can be feasible by using mainstream Grid technologies, which have been shown to have some Significant advantages over non-Grid based approaches

Grid-based semantic integration of heterogeneous data resources : implementation on a HealthGrid

The semantic integration of geographically distributed and heterogeneous data resources still remains a key challenge in Grid infrastructures. Today's mainstream Grid technologies hold the promise to meet this challenge in a systematic manner, making data applications more scalable and manageable. The thesis conducts a thorough investigation of the problem, the state of the art, and the related technologies, and proposes an Architecture for Semantic Integration of Data Sources (ASIDS) addressing the semantic heterogeneity issue. It defines a simple mechanism for the interoperability of heterogeneous data sources in order to extract or discover information regardless of their different semantics. The constituent technologies of this architecture include Globus Toolkit (GT4) and OGSA-DAI (Open Grid Service Architecture Data Integration and Access) alongside other web services technologies such as XML (Extensive Markup Language). To show this, the ASIDS architecture was implemented and tested in a realistic setting by building an exemplar application prototype on a HealthGrid (pilot implementation). The study followed an empirical research methodology and was informed by extensive literature surveys and a critical analysis of the relevant technologies and their synergies. The two literature reviews, together with the analysis of the technology background, have provided a good overview of the current Grid and HealthGrid landscape, produced some valuable taxonomies, explored new paths by integrating technologies, and more importantly illuminated the problem and guided the research process towards a promising solution. Yet the primary contribution of this research is an approach that uses contemporary Grid technologies for integrating heterogeneous data resources that have semantically different. data fields (attributes). It has been practically demonstrated (using a prototype HealthGrid) that discovery in semantically integrated distributed data sources can be feasible by using mainstream Grid technologies, which have been shown to have some Significant advantages over non-Grid based approaches.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Studies on distributed approaches for large scale multi-criteria protein structure comparison and analysis

Protein Structure Comparison (PSC) is at the core of many important structural biology problems. PSC is used to infer the evolutionary history of distantly related proteins; it can also help in the identification of the biological function of a new protein by comparing it with other proteins whose function has already been annotated; PSC is also a key step in protein structure prediction, because one needs to reliably and efficiently compare tens or hundreds of thousands of decoys (predicted structures) in evaluation of 'native-like' candidates (e.g. Critical Assessment of Techniques for Protein Structure Prediction (CASP) experiment). Each of these applications, as well as many others where molecular comparison plays an important role, requires a different notion of similarity, which naturally lead to the Multi-Criteria Protein Structure Comparison (MC-PSC) problem. ProCKSI (www.procksi.org), was the first publicly available server to provide algorithmic solutions for the MC-PSC problem by means of an enhanced structural comparison that relies on the principled application of information fusion to similarity assessments derived from multiple comparison methods (e.g. USM, FAST, MaxCMO, DaliLite, CE and TMAlign). Current MC-PSC works well for moderately sized data sets and it is time consuming as it provides public service to multiple users. Many of the structural bioinformatics applications mentioned above would benefit from the ability to perform, for a dedicated user, thousands or tens of thousands of comparisons through multiple methods in real-time, a capacity beyond our current technology. This research is aimed at the investigation of Grid-styled distributed computing strategies for the solution of the enormous computational challenge inherent in MC-PSC. To this aim a novel distributed algorithm has been designed, implemented and evaluated with different load balancing strategies and selection and configuration of a variety of software tools, services and technologies on different levels of infrastructures ranging from local testbeds to production level eScience infrastructures such as the National Grid Service (NGS). Empirical results of different experiments reporting on the scalability, speedup and efficiency of the overall system are presented and discussed along with the software engineering aspects behind the implementation of a distributed solution to the MC-PSC problem based on a local computer cluster as well as with a GRID implementation. The results lead us to conclude that the combination of better and faster parallel and distributed algorithms with more similarity comparison methods provides an unprecedented advance on protein structure comparison and analysis technology. These advances might facilitate both directed and fortuitous discovery of protein similarities, families, super-families, domains, etc, and also help pave the way to faster and better protein function inference, annotation and protein structure prediction and assessment thus empowering the structural biologist to do a science that he/she would not have done otherwise

Studies on distributed approaches for large scale multi-criteria protein structure comparison and analysis

Protein Structure Comparison (PSC) is at the core of many important structural biology problems. PSC is used to infer the evolutionary history of distantly related proteins; it can also help in the identification of the biological function of a new protein by comparing it with other proteins whose function has already been annotated; PSC is also a key step in protein structure prediction, because one needs to reliably and efficiently compare tens or hundreds of thousands of decoys (predicted structures) in evaluation of 'native-like' candidates (e.g. Critical Assessment of Techniques for Protein Structure Prediction (CASP) experiment). Each of these applications, as well as many others where molecular comparison plays an important role, requires a different notion of similarity, which naturally lead to the Multi-Criteria Protein Structure Comparison (MC-PSC) problem. ProCKSI (www.procksi.org), was the first publicly available server to provide algorithmic solutions for the MC-PSC problem by means of an enhanced structural comparison that relies on the principled application of information fusion to similarity assessments derived from multiple comparison methods (e.g. USM, FAST, MaxCMO, DaliLite, CE and TMAlign). Current MC-PSC works well for moderately sized data sets and it is time consuming as it provides public service to multiple users. Many of the structural bioinformatics applications mentioned above would benefit from the ability to perform, for a dedicated user, thousands or tens of thousands of comparisons through multiple methods in real-time, a capacity beyond our current technology. This research is aimed at the investigation of Grid-styled distributed computing strategies for the solution of the enormous computational challenge inherent in MC-PSC. To this aim a novel distributed algorithm has been designed, implemented and evaluated with different load balancing strategies and selection and configuration of a variety of software tools, services and technologies on different levels of infrastructures ranging from local testbeds to production level eScience infrastructures such as the National Grid Service (NGS). Empirical results of different experiments reporting on the scalability, speedup and efficiency of the overall system are presented and discussed along with the software engineering aspects behind the implementation of a distributed solution to the MC-PSC problem based on a local computer cluster as well as with a GRID implementation. The results lead us to conclude that the combination of better and faster parallel and distributed algorithms with more similarity comparison methods provides an unprecedented advance on protein structure comparison and analysis technology. These advances might facilitate both directed and fortuitous discovery of protein similarities, families, super-families, domains, etc, and also help pave the way to faster and better protein function inference, annotation and protein structure prediction and assessment thus empowering the structural biologist to do a science that he/she would not have done otherwise

New Statistical Algorithms for the Analysis of Mass Spectrometry Time-Of-Flight Mass Data with Applications in Clinical Diagnostics

Mass spectrometry (MS) based techniques have emerged as a standard forlarge-scale protein analysis. The ongoing progress in terms of more sensitive machines and improved data analysis algorithms led to a constant expansion of its fields of applications. Recently, MS was introduced into clinical proteomics with the prospect of early disease detection using proteomic pattern matching. Analyzing biological samples (e.g. blood) by mass spectrometry generates mass spectra that represent the components (molecules) contained in a sample as masses and their respective relative concentrations. In this work, we are interested in those components that are constant within a group of individuals but differ much between individuals of two distinct groups. These distinguishing components that dependent on a particular medical condition are generally called biomarkers. Since not all biomarkers found by the algorithms are of equal (discriminating) quality we are only interested in a small biomarker subset that - as a combination - can be used as a fingerprint for a disease. Once a fingerprint for a particular disease (or medical condition) is identified, it can be used in clinical diagnostics to classify unknown spectra. In this thesis we have developed new algorithms for automatic extraction of disease specific fingerprints from mass spectrometry data. Special emphasis has been put on designing highly sensitive methods with respect to signal detection. Thanks to our statistically based approach our methods are able to detect signals even below the noise level inherent in data acquired by common MS machines, such as hormones. To provide access to these new classes of algorithms to collaborating groups we have created a web-based analysis platform that provides all necessary interfaces for data transfer, data analysis and result inspection. To prove the platform's practical relevance it has been utilized in several clinical studies two of which are presented in this thesis. In these studies it could be shown that our platform is superior to commercial systems with respect to fingerprint identification. As an outcome of these studies several fingerprints for different cancer types (bladder, kidney, testicle, pancreas, colon and thyroid) have been detected and validated. The clinical partners in fact emphasize that these results would be impossible with a less sensitive analysis tool (such as the currently available systems). In addition to the issue of reliably finding and handling signals in noise we faced the problem to handle very large amounts of data, since an average dataset of an individual is about 2.5 Gigabytes in size and we have data of hundreds to thousands of persons. To cope with these large datasets, we developed a new framework for a heterogeneous (quasi) ad-hoc Grid - an infrastructure that allows to integrate thousands of computing resources (e.g. Desktop Computers, Computing Clusters or specialized hardware, such as IBM's Cell Processor in a Playstation 3)