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Primary brain tumours are the most common solid tumours found in children and are an important cause of morbidity and mortality. Magnetic resonance imaging (MRI) is commonly used for non-invasive early-detection, diagnosis, delineation of tumours for treatment planning and assessment of post treatment changes. Different MRI modalities provide complementary contrast of tumour tissues, which can have varying degrees of heterogeneity and diffusivity in different tumour types. A variety of texture analysis methods have been shown to reveal tumour histological types. It is hypothesized that textural features, based on conventional and diffusion MRI modalities, would differentiate the characteristics of tumours. Tumour extraction is also a significant procedure needed to obtain a true tumour region. Semi-automated segmentation methods were applied, in comparison with the gold standard of manual segmentation by an expert, in order to speed up a manual segmentation approach and reduce any bias effects. In this study, we present an automatic processing pipeline for the characterization of brain tumours, based on texture analysis. We apply this to a multi-centre dataset of paediatric brain tumours and investigate the accuracy of tumour classification, based on textural features of diffusion and conventional MR images.

Imaging is a key component in the management of brain tumours, with MRI being the preferred modality for most clinical scenarios. However, although conventional MRI provides mainly structural information, such as tumour size and location, it leaves many important clinical questions, such as tumour type, aggressiveness and prognosis, unanswered. An increasing number of studies have shown that additional information can be obtained using functional imaging methods (which probe tissue properties), and that these techniques can give key information of clinical importance. These techniques include diffusion imaging, which can assess tissue structure, and perfusion imaging and magnetic resonance spectroscopy, which measures tissue metabolite profiles. Tumour metabolism can also be investigated using PET, with 18F-deoxyglucose being the most readily available tracer. This Review discusses these methods and the studies that have investigated their clinical use. A strong emphasis is placed on the measurement of quantitative parameters, which is a move away from the qualitative nature of conventional radiological reporting and presents major challenges, particularly for multicentre studies.

Magnetic resonance spectroscopy can provide noninvasive metabolite profiles of childhood brain tumors and these are highly characteristic for tumor type. This information is increasingly being used to provide a noninvasive diagnostic aid but since tumor pathologies differ in children to adults, child specific classifiers are required. Despite the strong dependence of the MRS metabolite profile on tumor type, some metabolites are also biomarkers of prognosis both within and across tumor groups. Some evidence is also emerging that MRS can also provide biomarkers of treatment response where prior to changes on conventional MRI.

In recent years, there has been widespread interest and a large number of publications on the application of graph theory techniques into constructing and analyzing biologically-informed gene networks from cancer cell line data sets. Current research efforts have predominantly looked at an overall static, topological, representation of the network, and have not investigated the application of graph theoretical techniques to evolutionary investigations of cancer. A number of these studies have used graph theory metrics, such as degree, betweenness, and closeness centrality, to identify important hub genes in these networks. However, these have not fully investigated the importance of genes across the different stages of the disease. Previous human glioblastoma publications have identified four subtypes of glioblastoma in adults, based on signature genes. In one such publication, Verhaak et al. found that the subtypes correspond to a narrow median survival range, from 11.3 months for the most aggressive subtype, to 13.1 months for the least aggressive one. In this work, we present an evolutionary graph theory study of glioblastoma based on survival data categorization, confirming genes associated with different survival times identified using established graph theory metrics. The work is extending the application of graph theory approaches to evolutionary studies of cancer cell line data.

Heterogeneous data models and coding schemes for electronic health records present challenges for automated search across distributed data sources. This paper describes a loosely coupled software framework based on the terminology controlled approach to enable the interoperation between the search interface and heterogeneous data sources. Software components interoperate via common terminology service and abstract criteria model so as to promote component reuse and incremental system evolution.

Interoperability and reuse of healthcare information, for patient care and clinical research, rely on standardised approaches in its representation. The medical domain is rich with terminologies and dictionaries to support the representation of clinical data, but these are not necessarily interoperable. Secondary care research has long been conducted with study-specific requirements, and the valuable information collected was, however, difficult to reuse and share due to incomplete data collection and its non-standard representation. As a way to resolve some of these issues, we are designing and building sustainable database applications that clinicians and researchers alike can use as research registries, with the main aim to have research-quality healthcare information for future research studies and trials. This paper looks at a case study of how these applications are being developed in Central England through the use of controlled vocabularies. Specialty teams are keen to improve the interoperability, sharing and reuse of health information within and across specialties.

In the United Kingdom (UK), local initiatives have started to federate electronic healthcare records from different primary care clinical systems, mainly for the purposes of ensuring that health care services effectively meet the needs of the population. The use of such information is being investigated for clinical research, notably in patient cohort identification and recruitment. To achieve these aims, it is essential that the information from different systems can be searched from a single interface. While interoperability is a widely researched topic, interoperable methods and data sources in primary care are largely missing. This paper describes our approach to enabling primary care data in England to be searchable on a platform developed for performing large national collaborative primary care research studies throughout the United States.

Effects of the identity and load of items in working memory (WM) on visual attention were examined. With a short interval between the WM item and a subsequent search task, there were effects of both load (slowed overall reaction times, RTs, in a WM condition relative to a mere repetition baseline) and identity (search RTs were affected by re-presentation of the item in WM in the search display). As the time to encode the initial display increased, the effects of load decreased while the effect of identity remained. The data indicate that the identity of stimuli in WM can affect the subsequent deployment of attention even when time is allowed for consolidation of the stimuli in WM, and that the WM effects are not causally related to the presence of cognitive load. The results are consistent with the identity of stimuli in WM modulating attention post the memory consolidation stage.

Patient identification and consequent recruitment in clinical trials is normally preceded with searches on electronic health record (EHR) systems. Query results may be collated across multiple health organisations and specialties. In such scenarios, a prime concern is the possibility of systems and their users inadvertently or otherwise impinging on the privacy of patients. Access to patient data is crucial for research purposes, but the degree of access must be controlled in such a way that it conforms to agreed legal, organisational and ethical policies. In this paper, we present a proposed model for managing a dynamic matrix of roles and data access privileges within the context of research systems in secondary care.

Introduction: Evidence-based medicine (EBM) improves the quality of health care. Courses on how to teach EBM in practice are available, but knowledge does not automatically imply its application in teaching. We aimed to identify and compare barriers and facilitators for teaching EBM in clinical practice in various European countries. Methods: aEuro integral A questionnaire was constructed listing potential barriers and facilitators for EBM teaching in clinical practice. Answers were reported on a 7-point Likert scale ranging from not at all being a barrier to being an insurmountable barrier. Results: aEuro integral The questionnaire was completed by 120 clinical EBM teachers from 11 countries. Lack of time was the strongest barrier for teaching EBM in practice (median 5). Moderate barriers were the lack of requirements for EBM skills and a pyramid hierarchy in health care management structure (median 4). In Germany, Hungary and Poland, reading and understanding articles in English was a higher barrier than in the other countries. Conclusion: aEuro integral Incorporation of teaching EBM in practice faces several barriers to implementation. Teaching EBM in clinical settings is most successful where EBM principles are culturally embedded and form part and parcel of everyday clinical decisions and medical practice

This paper presents an adapted version of the Unified Theory of Acceptance and Use of Technology Model to be utilised as a validation tool of captured user needs and requirements of particular interactive software technologies, within the framework of Clinical Trial Management Systems (CTMS). In particular, this model is used to assess the users' acceptance and technology adoption of specific CTMS modules of the electronic Primary Care Research Network (ePCRN) Clinical Trial Management Framework System. We present modifications on the variable of the key constructs of UTAUT, while we introduce our own moderating factors for the model in the context of validating an eligibility criteria tool for primary care and community-based clinical research.

Background: Breast cancer (BC) accounts for one-third of all cases of cancer in women in the UK. Current strategies for the detection of BC recurrence include computed tomography (CT), magnetic resonance imaging (MRI) and bone scintigraphy. Positron emission tomography (PET) and, more recently, positron emission tomography/computed tomography (PET/CT) are technologies that have been shown to have increasing relevance in the detection and management of BC recurrence. Objective: To review the accuracy of PET and PET/CT for the diagnosis of BC recurrence by assessing their value compared with current practice and compared with each other. Data sources: MEDLINE and EMBASE were searched from inception to May 2009. Study selection: Studies were included if investigations used PET or PET/CT to diagnose BC recurrence in patients with a history of BC and if the reference standard used to define the true disease status was histological diagnosis and/or long-term clinical follow-up. Studies were excluded if a non-standard PET or PET/CT technology was used, investigations were conducted for screening or staging of primary breast cancer, there was an inadequate or undefined reference standard, or raw data for calculation of diagnostic accuracy were not available. STUDY APPRAISAL: Quality assessment and data extraction were performed independently by two reviewers. Direct and indirect comparisons were made between PET and PET/CT and between these technologies and methods of conventional imaging, and meta-analyses were carried out. Analysis was conducted separately on patient- and lesion-based data. Subgroup analysis was conducted to investigate variation in the accuracy of PET in certain populations or contexts and sensitivity analysis was conducted to examine the reliability of the primary outcome measures. Results: Of the 28 studies included in the review, 25 presented patient-based data and 7 presented lesion-based data for PET and 5 presented patient-based data and 1 presented patient- and lesion-based data for PET/CT; 16 studies conducted direct comparisons with 12 comparing the accuracy of PET or PET/CT with conventional diagnostic tests and 4 with MRI. For patient-based data (direct comparison) PET had significantly higher sensitivity [89%, 95% confidence interval (CI) 83% to 93% vs 79%, 95% CI 72% to 85%, relative sensitivity 1.12, 95% CI 1.04 to 1.21, p = 0.005] and significantly higher specificity (93%, 95% CI 83% to 97% vs 83%, 95% CI 67% to 92%, relative specificity 1.12, 95% CI 1.01 to 1.24, p = 0.036) compared with conventional imaging tests (CITs)--test performance did not appear to vary according to the type of CIT tested. For patient-based data (direct comparison) PET/CT had significantly higher sensitivity compared with CT (95%, 95% CI 88% to 98% vs 80%, 95% CI 65% to 90%, relative sensitivity 1.19, 95% CI 1.03 to 1.37, p = 0.015), but the increase in specificity was not significant (89%, 95% CI 69% to 97% vs 77%, 95% CI 50% to 92%, relative specificity 1.15, 95% CI 0.95 to 1.41, p = 0.157). For patient-based data (direct comparison) PET/CT had significantly higher sensitivity compared with PET (96%, 95% CI 90% to 98% vs 85%, 95% CI 77% to 91%, relative sensitivity 1.11, 95% CI 1.03 to 1.18, p = 0.006), but the increase in specificity was not significant (89%, 95% CI 74% to 96% vs 82%, 95% CI 64% to 92%, relative specificity 1.08, 95% CI 0.94 to 1.20, p = 0.267). For patient-based data there were no significant differences in the sensitivity or specificity of PET when compared with MRI, and, in the one lesion based study, there was no significant differences in the sensitivity or specificity of PET/CT when compared with MRI. Limitations: Studies reviewed were generally small and retrospective and this may have limited the generalisability of findings. Subgroup analysis was conducted on the whole set of studies investigating PET and was not restricted to comparative studies. Conventional imaging studies that were not compared with PET or PET/CT were excluded from the review. Conclusions: Available evidence suggests that for the detection of BC recurrence PET, in addition to conventional imaging techniques, may generally offer improved diagnostic accuracy compared with current standard practice. However, uncertainty remains around its use as a replacement for, rather than an add-on to, existing imaging technologies. In addition, PET/CT appeared to show clear advantage over CT and PET alone for the diagnosis of BC recurrence. FUTURE WORK: Future research should include: prospective studies with patient populations clearly defined with regard to their clinical presentation; a study of diagnostic accuracy of PET/CT compared with conventional imaging techniques; a study of PET/CT compared with whole-body MRI; studies investigating the possibility of using PET/CT as a replacement for rather than an addition to CITs; and using modelling of the impact of PET/CT on patient outcomes to inform the possibility of conducting large-scale intervention trials.

Totally Automatic Robust Quantitation in NMR (TARQUIN), a new method for the fully automatic analysis of short echo time in vivo (1)H Magnetic resonance spectroscopy is presented. Analysis is performed in the time domain using non-negative least squares, and a new method for applying soft constraints to signal amplitudes is used to improve fitting stability. Initial point truncation and Hankel singular value decomposition water removal are used to reduce baseline interference. Three methods were used to test performance. First, metabolite concentrations from six healthy volunteers at 3 T were compared with LCModel™. Second, a Monte-Carlo simulation was performed and results were compared with LCModel™ to test the accuracy of the new method. Finally, the new algorithm was applied to 1956 spectra, acquired clinically at 1.5 T, to test robustness to noisy, abnormal, artifactual, and poorly shimmed spectra. Discrepancies of less than approximately 20% were found between the main metabolite concentrations determined by TARQUIN and LCModel™ from healthy volunteer data. The Monte-Carlo simulation revealed that errors in metabolite concentration estimates were comparable with LCModel™. TARQUIN analyses were also found to be robust to clinical data of variable quality. In conclusion, TARQUIN has been shown to be an accurate and robust algorithm for the analysis of magnetic resonance spectroscopy data making it suitable for use in a clinical setting.

Over the past decade, evidence-based medicine (EBM) has gained recognition as a means to improve the quality of health care provision. However, little is known about learning opportunities to acquire EBM-associated skills. The EUebm-Unity partnership explored current educational activities for EBM practice for doctors across Europe.We surveyed organizations offering postgraduate EBM courses across Europe inquiring about their course programme, teaching content and strategies, and interest in a Europe-wide curriculum in EBM.One hundred and fifty-six organizers in eight European countries reported 403 courses that had started first-time from 1996 to 2006. Despite a steady increase, in absolute terms, the frequency of courses was low and varied from 1 first-time offering of a course per 640 doctors (Spain) to 1 first-time offering per 5600 doctors (Austria) over 10 years. Most adopted the McMaster EBM teaching concept of small group, problem-based learning focussing on interventions, diagnostic tests and guidelines, and included efforts to link EBM to patient care. Teaching staff consisted of doctors from academic and non-academic settings, supported by methodologists. Efforts to formally integrate EBM in postgraduate activities were only partially successful. Most organizations welcomed a standardized European qualification in EBM. A limitation of the survey is the lack of follow-up information about the continuation of courses following the first-time offering.All countries offer some EBM courses with varying teaching intensity. Learning opportunities are insufficient to ensure widespread dissemination of knowledge and skills. Most countries welcome more efforts to develop inexpensive and feasible educational activities at a postgraduate level.

Independent component analysis (ICA) can automatically extract individual metabolite, macromolecular and lipid (MMLip) components from a series of in vivo MR spectra. The traditional feature extraction (FE)-based ICA approach is limited, in that a large sample size is required and a combination of metabolite and MMLip components can appear in the same independent component. The alternative ICA approach, based on blind source separation (BSS), is weak when dealing with overlapping peaks. Combining the advantages of both BSS and FE methods may lead to better results. Thus, we propose an ICA approach involving a hybrid of the BSS and FE techniques for the automated decomposition of a series of MR spectra. Experiments were performed on synthesised and patient in vivo childhood brain tumour MR spectra datasets. The hybrid ICA method showed an improvement in the decomposition ability compared with BSS-ICA or FE-ICA, with an increased correlation between the independent components and simulated metabolite and MMLip signals. Furthermore, we were able to automatically extract metabolites from the patient MR spectra dataset that were not in commonly used basis sets (e.g. guanidinoacetate).

Magnetic resonance spectroscopy (MRS) has been successful in characterising a range of brain tumours and is a useful aid to non-invasive diagnosis. The pineal region poses considerable surgical challenges and a major surgical resection is not required in the management of all tumours. Improved non-invasive assessment of pineal region tumours would be of considerable benefit.Single voxel MRS (TE 30 ms, TR 1500, 1.5 T) was performed on 15 pineal tumours: 5 germinomas, 1 non-germinomatous secreting germ cell tumour (GCT), 2 teratomas, 5 pineoblastomas, 1 pineal parenchymal tumour (PPT) of intermediate differentiation and 1 pineocytoma. Two germinomas outside the pineal gland were also studied. Metabolite, lipid and macromolecule concentrations were determined with LCModel™.Germ cell tumours had significantly higher lipid and macromolecule concentrations than other tumours (t-test; P0.05). The teratomas had significantly lower total choline and creatine levels than germinomas (z test; P0.05). Taurine was convincingly detected in germinomas as well as PPTs.Magnetic resonance spectroscopy is useful for characterising pineal region tumours, aiding the non-invasive diagnosis and giving additional biological insight.

Magnetic Resonance Imaging (MRI) produces high resolution images of anatomical features such as brain tumours, due to the contrast indicators of different types of tissues. Magnetic Resonance Spectroscopy (MRS) can provide the metabolic characterisation of tumours that MRI cannot. The combination of the elements of anatomical features and metabolic information are most useful in a clinical practice, particularly in the context of brain tumours where biopsy carries additional difficulties because of dangers inherent in inter-cranial surgery. The aim of this paper is to investigate how to combine MRI and MRS in the context of brain tumour research. The location of the MRS voxel can provide important diagnosis information of the tumour from both imaging and spectroscopy sides. A developmental framework has been implemented for the localization, registration and visualisation of MRS voxels with MRI images. The proposed work can be used for further image analysis and spectroscopy representation.

Management of brain tumours in children would benefit from improved non-invasive diagnosis, characterisation and prognostic biomarkers. Metabolite profiles derived from in-vivo MRS have been shown to provide such information. Studies indicate that using optimum a priori information on metabolite contents in the construction of linear combination (LC) models of MR spectra leads to improved metabolite profile estimation. Glycine (Gly) is usually neglected in such models due to strong overlap with myo-inositol (mI) and a low concentration in normal brain. However, biological studies indicate that Gly is abundant in high-grade brain tumours. This study aimed to investigate the quantitation of Gly in paediatric brain tumours using MRS analysed by LCModel™, and its potential as a non-invasive biomarker of malignancy. Single-voxel MRS was performed using PRESS (TR 1500 ms, TE 30 ms/135 ms) on a 1.5 T scanner. Forty-seven cases (18 high grade (HG), 17 low grade (LG), 12 ungraded) were retrospectively selected if both short-TE and long-TE MRS (n = 33) or short-TE MRS and high-resolution magic-angle spinning (HRMAS) of matched surgical samples (n = 15) were available. The inclusion of Gly in LCModel™ analyses led to significantly reduced fit residues for both short-TE and long-TE MRS (p

With the global distribution of scientific and software engineering skills and with the need to foster multidisciplinary research collaboration across organisations result in teams dispersed separated by time and distance. However to attain the potential benefits of such collaboration, there is a critical need for a better management of communication, knowledge and co-ordination across distributed teams. The importance of these factors is becoming increasingly known to organisations requiring them to develop methods and enabling mechanisms in need for more successful and efficient collaboration outcomes. This paper discusses and emphasises the importance of managing these factors in distributed software engineering projects based on experiences drawn from an international scientific research and software engineering project (ePCRN). It presents their impact on the collaborative process and how they may hinder the progress of the software development process. It also presents the methods and mechanisms used in the project to address some of these factors

Background: To evaluate the educational effects of a clinically integrated e-learning course for teaching basic evidence-based medicine (EBM) among postgraduates compared to a traditional lecture-based course of equivalent content. Methods: We conducted a cluster randomised controlled trial in the Netherlands and the UK involving postgraduate trainees in six obstetrics and gynaecology departments. Outcomes (knowledge gain and change in attitude towards EBM) were compared between the clinically integrated e-learning course (intervention) and the traditional lecture based course (control). We measured change from pre- to post-intervention scores using a validated questionnaire assessing knowledge (primary outcome) and attitudes (secondary outcome). Results: There were six clusters involving teaching of 61 postgraduate trainees (28 in the intervention and 33 in the control group). The intervention group achieved slightly higher scores for knowledge gain compared to the control, but these results were not statistically significant (difference in knowledge gain: 3.5 points, 95% CI -2.7 to 9.8, p = 0.27). The attitudinal changes were similar for both groups. Conclusion: A clinically integrated e-learning course was at least as effective as a traditional lecture based course and was well accepted. Being less costly than traditional teaching and allowing for more independent learning through materials that can be easily updated, there is a place for incorporating e-learning into postgraduate EBM curricula that offer on-the-job training for just-in-time learning. Trial registration: Trial registration number: ACTRN12609000022268.

Independent component analysis (ICA) has the potential of determining automatically the metabolite signals which make up MR spectra. However, the reliability with which this is accomplished and the optimal approach for investigating in vivo MRS have not been determined. Furthermore, the properties of ICA in brain tumour MRS with respect to dataset size and data quality have not been systematically explored. The two common techniques for applying ICA, blind source separation (BSS) and feature extraction (FE) were examined in this study using simulated data and the findings confirmed on patient data. Short echo time (TE 30 ms), low and high field (1.5 and 3 T) in vivo brain tumour MR spectra of childhood astrocytoma, ependymoma and medulloblastoma were generated by using a quantum mechanical simulator with ten metabolite and lipid components. Patient data (TE 30 ms, 1.5 T) were acquired from children with brain tumours. ICA of simulated data shows that individual metabolite components can be extracted from a set of MRS data. The BSS method generates independent components with a closer correlation to the original metabolite and lipid components than the FE method when the number of spectra in the dataset is small. The experiments also show that stable results are achieved with 300 MRS at an SNR equal to 10. The FE method is relatively insensitive to different ranges of full width at half maximum (FWHM) (from 0 to 3 Hz), whereas the BSS method degrades on increasing the range of FWHM. The peak frequency variations do not affect the results within the range of +/-0.08 ppm for the FE method, and +/-0.05 ppm for the BSS method. When the methods were applied to the patient dataset, results consistent with the synthesized experiments were obtained.

A number of algorithms designed to determine metabolite concentrations from in vivo (1)H MRS require a collection of single metabolite spectra, known as a basis set, which can be obtained experimentally or by simulation. It has been assumed that basis sets can be used interchangeably, but no systematic study has investigated the effects of small variations in basis functions on the metabolite values obtained. The aim of this study was to compare the results of simulated with experimental basis sets when used to fit short-TE (1)H MRS data of variable quality at 1.5 T. Two hundred and twelve paediatric brain tumour spectra were included in the analysis, and each was analysed twice with LCModel™ using a simulated and experimental basis set. To determine the influence of data quality on quantification, each spectrum was assessed and 152 were classified as being of 'good' quality. Bland-Altman statistics were used to measure the agreement between the two basis sets for all available spectra and only 'good'-quality spectra. Monte-Carlo simulations were performed to investigate the influence of minor shifts in metabolite frequencies on metabolite concentration estimates. All metabolites showed good agreement between the two basis sets, and the average metabolite limits of agreement were approximately ±3.84 mM for all available data and ±0.99 mM for good-quality data. Errors obtained from the Monte-Carlo analysis were found to be more accurate than the Cramer-Rao lower bounds (CRLB) for 12 of 15 metabolites when metabolite frequency shifting was considered. For the majority of purposes, a level of agreement of ±0.99 mM between simulated and experimental basis sets is sufficiently small for them to be used interchangeably. Multiple analyses using slightly modified basis sets may be useful in estimating fitting errors, which are not predicted by CRLBs.

Magnetic resonance (MR) imaging has a key role in the management of many childhood tumours. There is increasing interest in extending these investigations to MR techniques that give information on tumour biology in vivo . Magnetic resonance spectroscopy (MRS) is one such method and it provides information on tissue biochemistry. Promising results have been obtained from many preclinical and clinical studies, leading to an expectation that MRS will play a valuable clinical role. However, the role of MRS is not yet well defined and there is a paucity of data from multi-centre clinical trials. In this article we concentrate on MRS in paediatric oncology and provide some general guidance on current applications and outline areas that need to be developed further. Certain atomic nuclei (eg, 1H, 31P and 13C) possess a magnetic moment and when placed in a strong magnetic field will resonate at a particular radiofrequency that subtly depends upon the chemical environment. In MR spectroscopy, the frequencies and intensities of these resonances are measured and represented graphically in an MR spectrum. The most commonly available method clinically is 1H MRS, and the 1H spectrum is a biochemical profile of the small mobile metabolites and macromolecules present in the tissue. 1H MRS can be performed with a standard clinical MRI scanner as part of a conventional MRI investigation. An example 1H spectrum from normal brain is given in figure 1. The horizontal scale, in units of parts per million (ppm), represents signal frequency adjusted to be invariant to the strength of the magnetic field of the MR scanner. Each metabolite is identified by one or more peaks at specific ppm values with the areas under the peaks being proportional to the metabolite concentration. The main metabolites observed are N-acetyl aspartate (NAA), …

After a brief review of conventional approaches to shortest path routing an alternative algorithm that abstracts a network graph into a logical tree is introduced. The algorithm is based on the decomposition of a graph into its minimum cycle basis (a basis of the cycle vector space of a graph having least overall weight or length). A procedure that abstracts the cycles and their adjacencies into logical nodes and links correspondingly is introduced. These logical nodes and links form the next level logical graph. The procedure is repeated recursively, until a loop-free logical graph is derived. This iterative abstraction is called a logical network abstraction procedure and can be used to analyze network graphs for resiliency, as well as become the basis of a new routing methodology. Both these aspects of the logical network abstraction procedure are discussed in some detail.

BRIDG is a widely known domain model of protocol-driven biomedical/clinical research. During a project to design a clinical trials management system for primary care research we developed a standard, computable representation of an RCT--the Primary Care Research Object Model (PCROM). We compared the PCROM Model to BRIDG and found significant overlap of concepts but also several areas important to our work that were either not yet represented or represented quite differently in BRIDG.

Background: We developed and evaluated the outcomes of an e-learning course for evidence based medicine (EBM) training in postgraduate medical education in different languages and settings across five European countries. Methods: We measured changes in knowledge and attitudes with well-developed assessment tools before and after administration of the course. The course consisted of five e-learning modules covering acquisition (formulating a question and search of the literature), appraisal, application and implementation of findings from systematic reviews of therapeutic interventions, each with interactive audio-visual learning materials of 15 to 20 minutes duration. The modules were prepared in English, Spanish, German and Hungarian. The course was delivered to 101 students from different specialties in Germany (psychiatrists), Hungary (mixture of specialties), Spain (general medical practitioners), Switzerland (obstetricians-gynaecologists) and the UK (obstetricians-gynaecologists). We analysed changes in scores across modules and countries. Results: On average across all countries, knowledge scores significantly improved from pre- to post-course for all five modules (p < 0.001). The improvements in scores were on average 1.87 points (14% of total score) for module 1, 1.81 points (26% of total score) for module 2, 1.9 points (11% of total score) for module 3, 1.9 points (12% of total score) for module 4 and 1.14 points (14% of total score) for module 5. In the country specific analysis, knowledge gain was not significant for module 4 in Spain, Switzerland and the UK, for module 3 in Spain and Switzerland and for module 2 in Spain. Compared to pre-course assessment, after completing the course participants felt more confident that they can assess research evidence and that the healthcare system in their country should have its own programme of research about clinical effectiveness. Conclusion: E-learning in EBM can be harmonised for effective teaching and learning in different languages, educational settings and clinical specialties, paving the way for development of an international e-EBM course.

Direct infusion nanoelectrospray Fourier transform ion cyclotron resonance mass spectrometry (DI nESI FT-ICR MS) offers high mass accuracy and resolution for analyzing complex metabolite mixtures. High dynamic range across a wide mass range, however, can only be achieved at the expense of mass accuracy, since the large numbers of ions entering the ICR detector induce adverse space-charge effects. Here we report an optimized strategy for wide-scan DI nESI FT-ICR MS that increases dynamic range but maintains high mass accuracy. It comprises the collection of multiple adjacent selected ion monitoring (SIM) windows that are stitched together using novel algorithms. The final SIM-stitching method, derived from several optimization experiments, comprises 21 adjoining SIM windows each of width m/z 30 (from m/z 70 to 500; adjacent windows overlap by m/z 10) with an automated gain control (AGC) target of 1 x 10(5) charges. SIM-stitching and wide-scan range (WSR; Thermo Electron) were compared using a defined standard to assess mass accuracy and a liver extract to assess peak count and dynamic range. SIM-stitching decreased the maximum mass error by 1.3- and 4.3-fold, and increased the peak count by 5.3- and 1.8-fold, versus WSR (AGC targets of 1 x 10(5) and 5 x 10(5), respectively). SIM-stitching achieved an rms mass error of 0.18 ppm and detected over 3000 peaks in liver extract. This novel approach increases metabolome coverage, has very high mass accuracy, and at 5.5 min/sample is conducive for high-throughput metabolomics.

Proton magnetic resonance spectroscopy (MRS) measures concentrations of metabolites in vivo and provides a powerful method for identifying tumours. MRS has not entered routine clinical use partly due to the difficulty of analysing the spectra. To create a straightforward method for interpreting short-echo-time MRS of childhood cerebellar tumours. Single-voxel MRS (1.5-T Siemens Symphony NUM4, TR/TE 1,500/30 ms) was performed at presentation in 30 children with cerebellar tumours. The MRS results were analysed for comparison with histological diagnosis. Peak heights for N-acetyl aspartate (NAA), creatine (Cr), choline (Cho) and myo-inositol (mIns) were determined and receiver operator characteristic curves used to select ratios that best discriminated between the tumour types. The method was implemented by a group of clinicians and scientists, blinded to the results. A total of 27 MRS studies met the quality control criteria. NAA/Cr >4.0 distinguished all but one of the astrocytomas from the other tumours. A combination of Cr/Cho

Background: Over the last years key stake holders in the healthcare sector have increasingly recognised evidence based medicine (EBM) as a means to improving the quality of healthcare. However, there is considerable uncertainty about the best way to disseminate basic knowledge of EBM. As a result, huge variation in EBM educational provision, setting, duration, intensity, content, and teaching methodology exists across Europe and worldwide. Most courses for health care professionals are delivered outside the work context ('stand alone') and lack adaptation to the specific needs for EBM at the learners' workplace. Courses with modern 'adaptive' EBM teaching that employ principles of effective continuing education might fill that gap. We aimed to develop a course for post-graduate education which is clinically integrated and allows maximum flexibility for teachers and learners. Methods: A group of experienced EBM teachers, clinical epidemiologists, clinicians and educationalists from institutions from eight European countries participated. We used an established methodology of curriculum development to design a clinically integrated EBM course with substantial components of e-learning. An independent European steering committee provided input into the process. Results: We defined explicit learning objectives about knowledge, skills, attitudes and behaviour for the five steps of EBM. A handbook guides facilitator and learner through five modules with clinical and e-learning components. Focussed activities and targeted assignments round off the learning process, after which each module is formally assessed. Conclusion: The course is learner-centred, problem-based, integrated with activities in the workplace and flexible. When successfully implemented, the course is designed to provide just-in-time learning through on-the-job-training, with the potential for teaching and learning to directly impact on practice.

Description The Query Workbench is a tool of the TRANSFoRm project to support clinical studies and database research. It provides an interface to author, store and deploy queries of clinical data to identify potential subjects for clinical studies and can thus support the clinical study feasibility evaluation. The development of the Query Workbench system is driven by the TRANSFoRm Clinical Research Information Model (CRIM) [1], enabling the creation of a semantically aware software tool for

In terms of mounting a computer on the body, the computer's weight, size, shape, placement and method of attachment can elicit a number of effects. Inappropriate design may mean that the wearer is unable to perform specific tasks or achieve goals. Excessive stress on the body may result in perceptions of discomfort, which may in turn affect task performance, but ultimately raises issues of health and safety. This paper proposes a methodology for assessing the affects of wearing a computer in terms of physiological energy expenditure, the biomechanical effects due to changes in movement patterns, posture and perceptions of localised pain and discomfort due to musculoskeletal loading, and perceptions of well- being through comfort assessment. From ratings of these effects the paper proposes 5 levels to determine the wearability of a computer.

A novel procedure of summarizing and abstracting the topology and distributed statistical measures of routing performance for communication networks is presented. This procedure, called logical network abridgment (LNA), forms the basis of a novel resilient recursive routing (R3) protocol. In this paper, we investigate the usefulness of LNA in visualizing and defining the state of health of a communication network. Traditionally, connectivity and metrics (such as link utilization, end-to-end delay, etc.) are used to provide indications of the state of health of a network. However, connectivity alone tells us little about the intrinsic diversity of the network and therefore its resiliency to attacks or attrition. Similarly, individual localized or path specific metrics tell us little about the overall intrinsic capability of the network. The LNA procedure summarizes the metric of choice over the total network and is thus capable of describing the intrinsic state of its health. In the context of military command and control, as well as commercial network management, scenarios, operators wish to easily create well-designed networks, in terms of resiliency and performance. Furthermore, operators need to identify, in an intuitive manner, the vulnerabilities that exist in a network. In addition, the consequences of actions taken to remedy failures or strengthen resiliency are often time consuming to understand in a large distributed system. The LNA procedure offers a quick and reliable algorithmic visual tool to achieve these. The paper presents work funded by the US Air-Force Research Laboratory (AFRL-EOARD) that demonstrates the potential of network visualization and analysis through the proposed LNA procedure

This chapter explores the technological quest of virtual reality within the field of medicine. Although the author does not intend to provide an exhaustive review of the various health informatics applications of VR over the past 15 years of its development, he presents some of the major technological breakthroughs and their impact in the provision of healthcare services to the point-of-need (i.e., the patient).

Digital Medical Libraries. DL1 Medical image libraries: a vision for the future (S. Morris). DL2 Digital libraries - a quality concept (F. Norman). DL3 MIDRIB - A comprehensive medical images database (J. Szuscikiewicz). DL4 Indexing the Web? A Comparative study of three medical Web servers on the Internet: CliniWeb, Diseases, Disorders and Related Topics, OMNI (S. J. Darmoni and B. Thirion). DL5 The role of the Internet in medical decision making (M. Anderson, H. Moazamipour, D. Hudson and M. Cohen). Electronic Publishing in Medicine. EP1 Non-indexed medical journals in the Web: new perspectives in the medical literature (A. E. Germenis, P. A. Kokkinides and C. Stavropoulos-Giokas). EP2 Networking the neurological charities (T. Kelly and A. Billington). EP3 EQUIP Magazine on the World Wide Web (M. North). EP4 Electronic publishing over the Internet: an extension of research workshops (J. M. Jenkins). EP5 Casting our Net: transforming a hospital house journal into an electronic version for simultaneous publication on the World Wide Web (H. Gaston, S-A. Morley, C. Baldock). Medical Education. ME1 Telemedicine and the Internet: their role in continuing medical education (S. Groves-Phillips). ME2 A systematic methodology for assessing WWW medical education materials (E. Berry, C. Parker-Jones, R. G. Jones, P. J. R. Harkin, H. O. Horsfall, J. A. Nicholls and N. J. A. Cook). ME3 A cognitive apprenticeship approach to teaching medicine on the World Wide Web (Z. Al-Rawahi and M. Sharples). ME4 The present and future role of the Internet in undergraduate and postgraduate medical education (A. Colman, R. Hollingsworth and B. Richards). ME5 Virtual Medical Laboratory (G. H. Alusi, A. C. Tan, A. Linney, and A. Wright). ME6 Interactive intranet tutoring for medical image processing (T. N. Arvanitis, N. Papadopoulos, C. Baldock, and D. Watson). ME7 The Derweb project - Dental education resources on the Internet (L. G. Davis, R. B. Winstanley, R. Duffin, and A. Griffiths). ME8 Online clinical database as an education tool for maxillofacial surgery (R. P. Harper, A. M. Cherkashin, and M. L. Samchukov). ME9 The World Wide Web as a teaching medium for flexible fibre-optic endoscopy (A. Colman, B. Richards, and R. Lewis). ME10 WWW creates new interactive 3D graphics and collaborative environments for medical research and education (S. Samothrakis, T. N. Arvanitis, A. Plataniotis, M. D. J. McNeill, and P. F. Lister). ME11 Radiologic anatomy on the World-Wide-Web (B. K. Szabo1, and P. Milassin). ME12 A computerised intranet whiteboard: enabling distributed training for medical imaging reporting (S. R. Parsowith, and T. N. Arvanitis). Telemedicine. TM1 Analysis and design of telecommunication networks for applications in telemedicine (I. Soto, M. Rodriguez, E. Gago, E. Fernandez, M. de Cabo, M. J. Morales, and P. Palomo). TM2 Clinical evaluation of new teleradiology systems and concepts (M. Walz, K-J. Lehmann, R. Loose, R. Bolte, M. Schinkmann, G. Weisser, T. Hothorn, and M. Georgi). TM3 European Healthcare Telematics Observatory (G. De Moor, M. McCurry, M. Laires, and C. Thayer). Information Policies and Ethical Issues IP1 Official vs unofficial outbreak reporting through the Internet (J. Woodall). IP2 Lessons learned from the development of an Applications Tracking System in the pharmaceutical regulatory sector (A. Zenie, F. Argentesi, and K. de Neef). Internet Security IS1 Internet security: the myth of secure networking (S. Kingston). IS2 Security measures in open communication systems (R. Hanka, and I. E. Buchan). IS3 Security management in the medical environment (G. Butler, N. Jayaram and P. Morse). IS4 Models and issues in sharing health and social care data (P. A. Dearnley, and D. J. Smith). Access to Health and Medical Information AM1 Perspectives of a MEDINFONET (N. Jayaram and P. Morse). AM2 Evaluating the options for developing databases to support research-based medicine at the NHS Centre for Reviews and Dissemination (J. Glanville, and I. Smith). AM3 Health On the Net automated database of health and medical information (C. Boyer, O. Baujard, V. Baujard, S. Aurel, M. Selby, and R. D. Appel). AM4 BASCD surveys and computer communication (Z. J. Nugent). AM5 Experience of a local hospital with the Internet - Brighton Health Care NHS Trust World-Wide-Web pages (C. Baldock). AM6 HealthGate: Toward an access interface platform for health information networks (A. Alcolea, F. del Pozo, and E. J. Gomez). AM7 Orthopaedic Information on the Internet (J. F. M. Clough). AM8 WWW access to radiological database using ACR index, Java/JavaScript and mSQL (T. Hothorn, M. Walz, J. Stahl, A. Bode, K. J. Lehmann, T. Werny, M. Schinkmann, R. Loose, and M. Georgi). AM9 Virtual Workspaces in I2Cnet (C. Chronaki, M. Tsiknakis, and S. Orphanoudakis). AM10 Using the Internet to support Celiacs: a case study based on US and UK samples (D. J. Brunner). AM11 Exchanging clinical knowledge via Internet (I. E. Buchan, and R. Hanka). Clinical Applications on the World Wide Web CA1 Demonstrating minimal invasive therapy over the Internet (R. Bennett, and P. T. Kirstein). CA2 An intranet database for pacemaker patients (R. A. Smith, T. N. Arvanitis, M. English, and R. Vincent). CA3 A heart sound Internet resource (J. E. Hebden, J. N. Torry, A. Haghighi-Mood, B. Tovar Corona, and B. Altabsheh). CA4 The Anaesthesia crtical incident reporting system: an experience based database (S. Staender, J. Davies, B. Helmreich, B. Sexton, and M. Kaufmann). CA5 Exploring novel chemotherapy treatments using the WWW (J. Boyle, D. Henderson, J. McCall, H. McLeod, and J. Usher). CA6 The Internet: a new patient recruitment resource (K. A. Getz). CA7 DESIRE for medical research (B. Loughlin, and G. Kernohan). CA8 The BSPE Web page: a means of research co-ordination, disease notification and Society housekeeping (S. D. North, J. K. H. Wales, and X. M. Shou). CA9 World Wide Web interface for advanced SPECT reconstruction algorithms implemented on a remote massively parallel computer (A. R. Formiconi, A. Passeri, M. R. Guelfi, M. Masoni, A. Pupi, U. Meldolesi, P. Malfetti, L. Calori, and A. Guidazzoli). CA10 Computer assisted medical diagnosis using the Web (L-P. Seka, A. Fresnel, D. Delamare, C. Riou, B. Pouliquen, R. Duvauferrier, and P. Le Beux). CA11 The Internet and randomised controlled trials (M. A. Kelly, and J. Oldham). CA12 A WWW-accessible knowledge base for the interpretation of hepatitis serologic tests (C. Chizzali-Bonfadin, K-P. Adlassnig, M. Kreihsl, A. Hatvan, and W. Horak). CA13 An Internet service for manipulating 3D models of human organs reconstructed from computer tomography and magnetic resonance imaging (G. Clapworthy, M. Krokos, and N. Vasilonikolidakis).

The traditional system design methodology (which follows a preliminary design, analysis, appraisal and redesign pattern) for automotive systems makes balancing contradicting design constraints such as cost, reliability and performance very difficult. Often all of the constraints are not met, and, even if they are, the resultant design may be sub-optimal. This paper outlines a new design approach using constraint satisfaction methods to create an optimal design, where all of the constraints are satisfied. Once the constraints are identified and represented in a suitable format, the design task can be semi-automated using a suitable algorithm. This paper explains how to identify and represent constraints in an automotive problem, the algorithms that can be used to solve the design problem, and how the outcome can be used as an extension to the existing design methodology. Finally, a high-level design for the implementation of the automation process and details of an initial prototype are given.

In order to develop effective virtual reality training systems for surgery there is a need to provide appropriate sensory and performance feedback to the user. This paper aims to demonstrate a method by which performance data can be collected. This is used to investigate the effect of haptic feedback on performance. A PHANTOM desktop device was used in conjunction with a suturing simulation A pair of needle-holders was instrumented with strain gauges and attached to the stylus of the PHANTOM allowing the measurement of force application and time. Suturing performance was evaluated in terms of stitch completion time, peak force application, and the length and straightness of the stitch. The effect of the level of force feedback provided by the simulation and performance over time was considered. The results indicate that the presence of force feedback affected task completion time, peak force application and the straightness of the stitch. Task completion time was shown to increase with the level of force feedback provided. Performance was seen to improve over time in terms of task completion time and the accuracy ofthe stitch. The work has examined how the presence and level of force feedback affects performance of a simple task. The accuracy of haptic feedback is important in the design of surgical simulation systems to ensure effective training transfer. A data collection method by which objective performance evaluation can be made is demonstrated. The method can be applied to training using bench models, simulations and potentially in the operating theatre.

We propose a new charging scheme for multi-domain differentiated services (DiffServ) networks. Our scheme considers the existence of non-DiffServ networks on the route of transmission. The charging agent at the edge of the source domain inserts in the DiffServ traffic charging measurement (CM) packets which contain traffic and charging information. The CM packets are subsequently returned by the charging agents at the downstream DiffServ domains. The charges can be easily calculated according to the feedback information in the returned CM packets. In addition to the above, we propose two signaling mechanisms for our charging schemes. We show that our scheme is simple, fair and scalable.

This paper reports the development of smart clothing for an education application. Beginning with a brief review of a specific perspective on wearable computers (computers as clothing), the paper defines six key assumptions for this technology: computational simplicity of nodes, embedded systems, interconnection of nodes, use of sensors at nodes, use of sensors to define context, and personalisation. A specific example of smart clothing, the SensVest prototype is described in terms of the design process and current evaluation activity.

The Differentiated Service (DiffServ) model has been proposed as an efficient and scalable service architecture to deploy different services on the Internet. In this paper, we propose a new pricing model for DiffServ. We use a marking/dropping mechanism incorporated in our pricing scheme to apply pricing in congested DiffSery networks. The proposed scheme is simple to implement and can give users incentives to control their behaviours by charging the network resources they have used during periods of congestion, while a user does not have to pay fees when the price ceiling has been reached.

This paper describes a multistage perceptual quality assessment (MPQA) model for compressed images. The motivation for the development of a perceptual quality assessment is to measure (in)visible differences between original and processed images. The MPQA produces visible distortion maps and quantitative error measures informed by considerations of the human visual system (HVS). Original and decompressed images are decomposed into different spatial frequency bands and orientations modeling the human cortex. Contrast errors are calculated for each frequency and orientation, and masked as a function of contrast sensitivity and background uncertainty. Spatially masked contrast error measurements are then made across frequency bands and orientations to produce a single perceptual distortion visibility map (PDVM). A perceptual quality rating (PQR) is calculated from the PDVM and transformed into a one to five scale, PQR/sub 1-5/, for direct comparison with the mean opinion score, generally used in subjective ratings. The proposed MPQA model is based on existing perceptual quality assessment models, while it is differentiated by the inclusion of contrast masking as a function of background uncertainty. A pilot study of clinical experiments on wavelet-compressed digital angiogram has been performed on a sample set of angiogram images to identify diagnostically acceptable reconstruction. Our results show that the PQR/sub 1-5/ of diagnostically acceptable lossy image reconstructions have better agreement with cardiologists' responses than objective error measurement methods, such as peak signal-to-noise ratio. A Perceptual thresholding and CSF-based Uniform quantization (PCU) method is also proposed using the vision models presented in this paper. The vision models are implemented in the thresholding and quantization stages of a compression algorithm and shown to produce improved compression ratio performance with less visible distortion than that of the embedded zerotrees wavelet (EZWs).

We present a possible way to extend queuing theory to account for interactions between adjacent queues in a packet-switched network. The interaction between queues arises because of the influence of the routing protocol on each switching decision and the stochastic nature of packet lengths and inter-arrival times.Both the methodology and the analysis tools are adaptations of methods of statistical mechanics and are presented in outline here. The justification for their use lies in experimental evidence given in [1,2,3] that aggregate, core-network IP traffic exhibits quasi-Markovian properties. In this paper, we focus on the interaction between pairs of queues, either in a cascaded arrangement, or connected to the same switching fabric, in the presence of an idealised routing protocol.

Studies of information and process modeling have demonstrated the importance and clinical impact of Picture Archiving and Communication Systems in the efficient operational management of imaging within the clinical setting. The appropriate identification of both clinical and technology requirements for the planning and deployment of such systems is essential to achieve cost-effectiveness in use. The understanding of the complexities of clinically viable network topologies and architectures for PACS can be achieved through realistic simulations and modeling. The purpose of this paper is to provide a methodology for modeling the DICOM session and application layer entities over Ethernet-based TCP/IP, by using the OPNET Modeler, and derive performance evaluation metrics for different PACS network topologies.© (2001) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

This paper presents the digital imaging results of a collaborative research project working toward the generation of an on-line interactive digital image database of signs from ancient cuneiform tablets. An important aim of this project is the application of forensic analysis to the cuneiform symbols to identify scribal hands. Cuneiform tablets are amongst the earliest records of written communication, and could be considered as one of the original information technologies; an accessible, portable and robust medium for communication across distance and time. The earliest examples are up to 5,000 years old, and the writing technique remained in use for some 3,000 years. Unfortunately, only a small fraction of these tablets can be made available for display in museums and much important academic work has yet to be performed on the very large numbers of tablets to which there is necessarily restricted access. Our paper will describe the challenges encountered in the 2D image capture of a sample set of tablets held in the British Museum, explaining the motivation for attempting 3D imaging and the results of initial experiments scanning the smaller, more densely inscribed cuneiform tablets. We will also discuss the tractability of 3D digital capture, representation and manipulation, and investigate the requirements for scaleable data compression and transmission methods. Additional information can be found on the project website: www.cuneiform.net© (2001) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

A key current objective in Medical Informatics is to impose structure on collections of healthcare data recorded in electronic form. A relevant example is the DICOM Structured Reporting (SR) data structure. Appropriate presentation of image and related data is essential for effective communication of information between clinicians. The effective use of display screens for clinical viewing of image and related data, within the imaging service department and in the broader domain, depends on the availability of means to ensure consistent presentation on different systems. Whilst some users, such as reporting clinicians, will need full control over selection of presentation content, layout and rendering parameters, others may be restricted to viewing data as originally prepared. In order to support this, generally accepted data structures are required that allow the specification of presentation details for medical image data, graphics data and text data. The implementation options for supporting the identified needs are discussed, including the scope for using XML to carry the structures and to support an open presentation model for use throughout all healthcare domains.

Improved presentation of the results of Diagnostic Medical Procedures must improve the communication of relevantinformation to the requesting clinician and so should improve the quality of healthcare. Facilities are now available to enablethe preparation of Multimedia Medical Reports. Conventional reports are frequently accompanied by relevant ProcedureProducts, such as images and curves. Benefit should be obtained if audible and visible annotation is included. Project Team34 of CEN/TC25 1 Draft First Working Document1 provides an overview of the use of Health Care Multimedia Reports. Theaim of this paper is to summarise the needs for the creation, modification and presentation of Multimedia Reports, to describea specific generic data structure for Procedure Product data, to describe one possible model for the Multimedia Report recordand to discuss the requirements for Multimedia Report authoring tools and presentation systems.Keywords: Healthcare reports, multimedia, rendering, World Wide Web, presentation, vector, image

This paper investigates the effects of lossless and lossy wavelet image compression methods on digital angiogram images. The requirements of suitable quality assessment methods for decompressed images are considered and the need for diagnostically relevant quality metrics in discussed. The results of experimental quality investigations, including expert cardiologists identifications of diagnostically acceptable quality boundaries, are presented and discussed.