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GASepo-a software solution for quantitative analysis of digital images in Epo doping control.

A software has been developed that is aimed at quantitative analysis of images acquired by isoelectric focusing and double blotting procedures used for recombinant erythropoietin doping control. It represents a unified and easy-to-use tool for Epo doping experts in WADA accredited laboratories. It is based on image segmentation philosophy that enables identification of individual bands whose characteristics are needed for evaluation of the Epo doping positivity criteria. Several modules implemented in the GASepo software include an original know how, in particular, the method of robust calculation of the cut-off line, band segmentation and classification algorithms. GASepo is being used in several doping control laboratories worldwide.

Algorithms↗

Clinical decision support software for management of chronic heart failure: development and evaluation.

OBJECTIVE: To develop and evaluate clinical decision support software (CDSS) to aid physicians treat patients with chronic heart failure (CHF). METHODS: The CDSS was developed after discussions with a multidisciplinary panel. Evaluation was performed in three stages over a 6 month period including an editorial check, one-to-one interviews with potential users and educational meetings with general practitioners (GPs), junior doctors and medical students during which the CDSS was assessed in a cross-over design against paper guidelines. Opinions of the CDSS and the computer literacy of the participants were assessed by questionnaire. RESULTS: There were several changes to the CDSS at various stages of development and evaluation. One-to-one interviews generated extensive qualitative feedback. GPs had lower computer literacy scores than junior doctors and students (both p<0.01). There were small trends when comparing the CDSS with paper guidelines. GPs scored less well (CDSS 75% vs. 80%, p=0.41), while junior doctors and medical students appeared to improve their scores (72%-84%, p=0.32 and 66%-77%, p=0.19, respectively). Most (70%) found the CDSS more useful than the written guidelines. CONCLUSION: Development of CDSS using guidelines and expert opinion requires a multidisciplinary iterative process of feedback and software adaptation. Barriers to implementation identified include lower computer literacy among GPs, a lack of complexity within CDSS in addressing non-medical needs of patients and a reluctance among medical staff to consult guidelines during patient consultations. Improving computer skills, integrating CDSS into referral pathways and requests for investigations may be ways of enhancing use of this emerging technology.

Cardiology↗

The "Sym'Previus" software, a tool to support decisions to the foodstuff safety.

Describing the Sym'Previus project, the software and its deliverable facilities is the aim of this present paper. This software concerns all the partners of the food industry who are involved in the management of food safety and allows food-borne pathogen behaviour in food to be predicted, as function of the environment (nature of the food, manufacturing process, conditions of conservation). This analysis of microbial behaviour has been possible thanks to the progress made in predictive microbiology since the 1980s. Sym'Previus offers to food industry professionals and their partners the possibility of applying this progress, by giving access to a database, to simulation systems and expertise.

Computer Simulation↗

Experiences of engineering Grid-based medical software.

OBJECTIVES: Grid-based technologies are emerging as potential solutions for managing and collaborating distributed resources in the biomedical domain. Few examples exist, however, of successful implementations of Grid-enabled medical systems and even fewer have been deployed for evaluation in practice. The objective of this paper is to evaluate the use in clinical practice of a Grid-based imaging prototype and to establish directions for engineering future medical Grid developments and their subsequent deployment. METHOD: The MammoGrid project has deployed a prototype system for clinicians using the Grid as its information infrastructure. To assist in the specification of the system requirements (and for the first time in healthgrid applications), use-case modelling has been carried out in close collaboration with clinicians and radiologists who had no prior experience of this modelling technique. A critical qualitative and, where possible, quantitative analysis of the MammoGrid prototype is presented leading to a set of recommendations from the delivery of the first deployed Grid-based medical imaging application. RESULTS: We report critically on the application of software engineering techniques in the specification and implementation of the MammoGrid project and show that use-case modelling is a suitable vehicle for representing medical requirements and for communicating effectively with the clinical community. This paper also discusses the practical advantages and limitations of applying the Grid to real-life clinical applications and presents the consequent lessons learned. CONCLUSIONS: The work presented in this paper demonstrates that given suitable commitment from collaborating radiologists it is practical to deploy in practice medical imaging analysis applications using the Grid but that standardization in and stability of the Grid software is a necessary pre-requisite for successful healthgrids. The MammoGrid prototype has therefore paved the way for further advanced Grid-based deployments in the medical and biomedical domains.

Humans↗

Pulser: user-friendly, graphical user-interface based software for controlling stimuli during data acquisition with Spike2 for Windows.

This paper describes software that runs in the Spike2 for Windows environment and provides a versatile tool for generating stimuli during data acquisition from the 1401 family of interfaces (CED, UK). A graphical user interface (GUI) is used to provide dynamic control of stimulus timing. Both single stimuli and trains of stimuli can be generated. The pulse generation routines make use of programmable variables within the interface and allow these to be rapidly changed during an experiment. The routines therefore provide the ease-of-use associated with external, stand-alone pulse generators. Complex stimulus protocols can be loaded from an external text file and facilities are included to create these files through the GUI. The software consists of a Spike2 script that runs in the host PC, and accompanying routines written in the 1401 sequencer control code, that run in the 1401 interface. Handshaking between the PC and the interface card are built into the routines and provides for full integration of sampling, analysis and stimulus generation during an experiment. Control of the 1401 digital-to-analogue converters is also provided; this allows control of stimulus amplitude as well as timing and also provides a sample-hold feature that may be used to remove DC offsets and drift from recorded data.

Action Potentials↗

Simple and inexpensive hardware and software method to measure volume changes in Xenopus oocytes expressing aquaporins.

Water channels (aquaporins) family members have been identified in central nervous system cells. A classic method to measure membrane water permeability and its regulation is to capture and analyse images of Xenopus laevis oocytes expressing them. Laboratories dedicated to the analysis of motion images usually have powerful equipment valued in thousands of dollars. However, some scientists consider that new approaches are needed to reduce costs in scientific labs, especially in developing countries. The objective of this work is to share a very low-cost hardware and software setup based on a well-selected webcam, a hand-made adapter to a microscope and the use of free software to measure membrane water permeability in Xenopus oocytes. One of the main purposes of this setup is to maintain a high level of quality in images obtained at brief intervals (shorter than 70 ms). The presented setup helps to economize without sacrificing image analysis requirements.

Animals↗

TOM software toolbox: acquisition and analysis for electron tomography.

Automated data acquisition procedures have changed the perspectives of electron tomography (ET) in a profound manner. Elaborate data acquisition schemes with autotuning functions minimize exposure of the specimen to the electron beam and sophisticated image analysis routines retrieve a maximum of information from noisy data sets. "TOM software toolbox" integrates established algorithms and new concepts tailored to the special needs of low dose ET. It provides a user-friendly unified platform for all processing steps: acquisition, alignment, reconstruction, and analysis. Designed as a collection of computational procedures it is a complete software solution within a highly flexible framework. TOM represents a new way of working with the electron microscope and can serve as the basis for future high-throughput applications.

Algorithms↗

SwarmPS: rapid, semi-automated single particle selection software.

Single particle analysis (SPA) coupled with high-resolution electron cryo-microscopy is emerging as a powerful technique for the structure determination of membrane protein complexes and soluble macromolecular assemblies. Current estimates suggest that approximately 10(4)-10(5) particle projections are required to attain a 3A resolution 3D reconstruction (symmetry dependent). Selecting this number of molecular projections differing in size, shape and symmetry is a rate-limiting step for the automation of 3D image reconstruction. Here, we present Swarm(PS), a feature rich GUI based software package to manage large scale, semi-automated particle picking projects. The software provides cross-correlation and edge-detection algorithms. Algorithm-specific parameters are transparently and automatically determined through user interaction with the image, rather than by trial and error. Other features include multiple image handling (approximately 10(2)), local and global particle selection options, interactive image freezing, automatic particle centering, and full manual override to correct false positives and negatives. Swarm(PS) is user friendly, flexible, extensible, fast, and capable of exporting boxed out projection images, or particle coordinates, compatible with downstream image processing suites.

Algorithms↗

RepeatAround: a software tool for finding and visualizing repeats in circular genomes and its application to a human mtDNA database.

RepeatAround is a Windows based software tool designed to find "direct repeats", "inverted repeats", "mirror repeats" and "complementary repeats", from 3 to 64 bp length, in circular genomes. It processes input files directly extracted from GenBank database, providing visualisation of the repeats location in the genomic structure, so that for instance, in most mtDNAs the user can check if the repeats are located in coding or non-coding region (and in the first case in which gene), and how far apart the repeat pair(s) are. Besides the visual tool, it provides other outputs in a spreadsheet containing information on the number and location of the repeats, facilitating graphic analyses. Several genomes can be inputed simultaneously, for phylogenetic comparison purposes. Other capabilities of the software are the generation of random circular genomes, for statistical evaluation of comparison between observed repeats distributions with their shuffled counterparts, as well as the search for specific motifs, allowing an easy confirmation of repeats flanking a newly detected rearrangement. As an example of the programme's applications we analysed the Direct Repeats distribution in a large human mtDNA database. Results showed that Direct Repeats, even the larger ones, are evenly distributed among the human mtDNA haplogroups, enabling us to state that, based only on the repetitive motifs, no haplogroup is particularly more or less prone to mtDNA macrodeletions.

Computational Biology↗

Parcellating the temporal lobes from magnetic resonance images using generic software in subjects at high risk of developing schizophrenia.

A number of reliable techniques have been described that can parcellate temporal neo-cortex from MRI images to preserve topographical characteristics of individual brains, but these tend to use in-house software. We describe here an adaptation of the methods previously described by Kim et al. [Kim, J.J., Crespo-Facorro, B., Andreasen, N.C., O'Leary, D.S., Zhang, B., Harris, G., Magnotta, V.A., 2000. An MRI-based parcellation method for the temporal lobe. Neuroimage 11, 271-288], but utilising commercially and, therefore, generally available software. Using Analyze, we traced individual sulci and identified coronal bounding planes, and used a combination of three orthogonal plane views, manual limit tracing and semi-automated edge detection to parcellate 13 sub-regions of temporal neo-cortex from sets of serial coronal slices. We applied this technique to the baseline scans of the first seven subjects in the Edinburgh High Risk Study (EHRS) who developed schizophrenia, and a matched group of healthy controls, to see if temporal lobe sub-regional volumes could predict the onset of schizophrenia. Two relatively inexperienced raters developed these techniques in a short time period, and intra-rater intra-class correlation coefficients (ICC) ranged from 0.56 to 0.99, while the mean inter-rater ICC was 0.90 (range 0.55-0.99). There were, however, no significant differences in temporal lobe sub-regional volumes between the two groups we examined. We have, therefore, developed a reliable parcellation technique that requires relatively little training. It is, however, a laborious process, and it remains uncertain whether it is more sensitive to early disease processes in pre-schizophrenia than are other image-analysis techniques.

Adolescent↗

Software extensions to UCSF chimera for interactive visualization of large molecular assemblies.

Many structures of large molecular assemblies such as virus capsids and ribosomes have been experimentally determined to atomic resolution. We consider four software problems that arise in interactive visualization and analysis of large assemblies: how to represent multimers efficiently, how to make cartoon representations, how to calculate contacts efficiently, and how to select subassemblies. We describe techniques and algorithms we have developed and give examples of their use. Existing molecular visualization programs work well for single protein and nucleic acid molecules and for small complexes. The methods presented here are proposed as features to add to existing programs or include in next-generation visualization software to allow easy exploration of assemblies containing tens to thousands of macromolecules. Our approach is pragmatic, emphasizing simplicity of code, reliability, and speed. The methods described have been distributed as the Multiscale extension of the UCSF Chimera (www.cgl.ucsf.edu/chimera) molecular graphics program.

Algorithms↗

Intelligent software for laboratory automation.

The automation of laboratory techniques has greatly increased the number of experiments that can be carried out in the chemical and biological sciences. Until recently, this automation has focused primarily on improving hardware. Here we argue that future advances will concentrate on intelligent software to integrate physical experimentation and results analysis with hypothesis formulation and experiment planning. To illustrate our thesis, we describe the 'Robot Scientist' - the first physically implemented example of such a closed loop system. In the Robot Scientist, experimentation is performed by a laboratory robot, hypotheses concerning the results are generated by machine learning and experiments are allocated and selected by a combination of techniques derived from artificial intelligence research. The performance of the Robot Scientist has been evaluated by a rediscovery task based on yeast functional genomics. The Robot Scientist is proof that the integration of programmable laboratory hardware and intelligent software can be used to develop increasingly automated laboratories.

Algorithms↗

BanTeC: a software tool for management of corneal transplantation.

BACKGROUND: Until recently, all cornea information at our tissue bank was managed manually, no specific database or computer tool had been implemented to provide electronic versions of documents and medical reports. The main objective of the BanTeC project was therefore to create a computerized system to integrate and classify all the information and documents used in the center in order to facilitate management of retrieved, transplanted corneal tissues. MATERIALS AND METHODS: We used the Windows platform to develop the project. Microsoft Access and Microsoft Jet Engine were used at the database level and Data Access Objects was the chosen data access technology. CONCLUSIONS: In short, the BanTeC software seeks to computerize the tissue bank. All the initial stages of the development have now been completed, from specification of needs, program design and implementation of the software components, to the total integration of the final result in the real production environment. BanTeC will allow the generation of statistical reports for analysis to improve our performance.

Corneal Transplantation↗

GenePalette: a universal software tool for genome sequence visualization and analysis.

To make effective use of the growing host of complete genome sequences, biologists must have easy-to-use software tools that allow them to visualize, analyze, and modify genome data in an interactive and generalized manner. In an effort to bridge the gap between genome and researcher, we have created GenePalette (www.genepalette.org), a desktop application that can access any genome sequence and display the positions of various features [e.g., transcription factor binding sites (TFBSs)] relative to the introns and exons of annotated genes. Written in Java, GenePalette can run on all Java-supporting operating systems (Mac, PC, Unix, Linux). Annotated sequence encompassing the majority of public genome data is rapidly retrieved from GenBank or Ensembl. The software provides intuitive access to the selected genomic region through three interface components: a colorful graphical display showing a schematic of genes and features; an annotated sequence view in which features and genes are highlighted directly on the sequence; and the selectable raw sequence. The three interface components are fully integrated and presented on one page, permitting the user to move easily between representations at different levels of resolution, ranging from kilobases to individual nucleotides. GenePalette is a particularly powerful platform for analyzing the organization of cis-regulatory elements and designing wet-lab experiments to investigate them.

Computational Biology↗

Laboratory cost control and financial management software.

Economical constraints within the health care system advocate the introduction of tighter control of costs in clinical laboratories. Detailed cost information forms the basis for cost control and financial management. Based on the cost information, proper decisions regarding priorities, procedure choices, personnel policies and investments can be made. This presentation outlines some principles of cost analysis, describes common limitations of cost analysis, and exemplifies use of software to achieve optimized cost control. One commercially available cost analysis software, LabCost, is described in some detail. In addition to provision of cost information, LabCost also serves as a general management tool for resource handling, accounting, inventory management and billing. The application of LabCost in the selection process of a new high throughput analyzer for a large clinical chemistry service is taken as an example for decisions that can be assisted by cost evaluation. It is concluded that laboratory management that wisely utilizes cost analysis to support the decision-making process will undoubtedly have a clear advantage over those laboratories that fail to employ cost considerations to guide their actions.

Cost Control↗

Evaluation of the Abbott system in maternal serum screening for Down syndrome: the AxSym analyzer, AFP and hCG reagents and Maciel Prenatal Interpretive Software.

Multi-marker maternal serum screening for Down syndrome in the second trimester is now part of routine care in many centers. Most protocols use a combination of hCG (or its free beta-subunit) and alpha-fetoprotein (AFP) or unconjugated estriol (UE3), or both. Risk calculation is based on these maternal serum marker values combined with maternal age and trisomy 21 maternal age-related risk. Computer programs are therefore necessary. Both technical and statistical efficiency are included in the final risk evaluation. We studied the Abbott system, comprising AxSym analyzer, AFP and hCG kits and Prenatal Interpretive Software (Maciel). Median values were established between 14 and 18 weeks of amenorrhea in a population of 1822 patients and in twin pregnancies in 157 cases. Forty maternal sera from trisomy 21 affected pregnancies were analyzed. Software was evaluated in a population of 429 patients and in 124 cases of trisomy 21. We conclude that this system constitutes an accurate and efficient method of maternal serum screening for Down syndrome.

Adult↗

Magnetic resonance imaging based volume estimation of ovarian tumours: use of a segmentation and 3D reformation software.

The application of a new segmentation software, Anatomatic in the evaluation of volumetric measurements of ovarian tumours and the new Medimag three-dimensional (3D) software in the evaluation of 3D image representation of ovarian tumours with 1.5 T magnetic resonance imaging (MRI) is described. Our goal was to compare MRI based volumetry with operative findings at laparotomy for six consecutive patients with suspected ovarian tumours. Volumetric analysis and three dimensional image reconstructions of the tumours were obtained. At laparotomy, the tumour sizes were measured in situ, and the volumes were calculated. Using Anatomatic, reproducible tumour volumes were achieved with ease and within a reasonably fast time in patients with ovarian tumours without ascites. Medimag helped achieve realistic 3D representations of the tumours. For the four solitary tumours segmentation based volumetry and laparotomy findings agreed in three cases. In one patient with an oval shaped tumour, the segmented volume was double as compared to that estimated at laparotomy. Of the two patients with multiple tumours, both patients had significant ascites, and volumetry misinterpreted the fluid as tumour cyst fluid and markedly overestimated the tumour size. In conclusion, the MRI based segmentation volumetry and 3D image reconstructions are rapid, and reproducible methods of measuring ovarian tumours in patients without significant ascites.

Adult↗

Software sensor for on-line estimation of the microbial activity in activated sludge systems.

This paper considers the design of a software sensor (or soft-sensor) for the on-line estimation of the biological activities of a colony of aerobic micro-organisms acting on activated sludge processes, where the carbonaceous waste degradation and nitrification processes are taken into account. These bioactivities are intimately related to the dissolved oxygen concentration. Two factors that affect the dynamics of the dissolved oxygen are the respiration rate or the oxygen uptake rate (OUR) and the oxygen transfer function (K(l)a). These items are challenging topics for the application of recursive identification due the nonlinear characteristic of the oxygen transfer function, and to the time-varying feature of the respiration rate. In this work, OUR and the oxygen transfer function are estimated through a software sensor, which is based on a modified version of the discrete extended Kalman filter. Numerical simulations are carried out in a predenitrifying activated sludge process benchmark and the obtained results demonstrate the applicability and efficiency of the proposed methodology, which should provide a valuable tool to supervise and control activated sludge processes.

Algorithms↗