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Practical experience with graphical user interfaces and object-oriented design in the clinical laboratory.

The computing strategy in our laboratories evolved from research in Artificial Intelligence, and is based on powerful software tools running on high performance desktop computers with a graphical user interface. This allows most tasks to be regarded as design problems rather than implementation projects, and both rapid prototyping and an object-oriented approach to be employed during the in-house development and enhancement of the laboratory information systems. The practical application of this strategy is discussed, with particular reference to the system designer, the laboratory user and the laboratory customer. Routine operation covers five departments, and the systems are stable, flexible and well accepted by the users. Client-server computing, currently undergoing final trials, is seen as the key to further development, and this approach to Pathology computing has considerable potential for the future.

Clinical Laboratory Information Systems↗

Client/Server computing: is this the future direction for the clinical laboratory?

One of the major trends in computing for the 1990s is the move towards distributed systems based on Client/Server architecture. Although a recent survey has suggested that some 41% of the major companies in the UK are either using or planning to adopt this new technology, there is little evidence at present of similar progress in the field of clinical laboratory computing. The Pathology Laboratories at St. Luke's Hospital have been developing in-house computer systems using object-oriented software tools since 1988, but these were initially based on conventional file sharing and suffered from poor performance under load. The conversion to Client/Server took place in March 1993 and the results have either met or exceeded all expectations. Our experience suggests that this approach may well be the way forward for the high performance but user-friendly laboratory systems of the future.

Clinical Laboratory Information Systems↗

An image processing system for digital chest X-ray images.

This paper investigates the requirements for image processing of digital chest X-ray images. These images are conventionally recorded on film and are characterised by large size, wide dynamic range and high resolution. X-ray detection systems are now becoming available for capturing these images directly in photoelectronic-digital form. In this report, the hardware and software facilities required for handling these images are described. These facilities include high resolution digital image displays, programmable video look up tables, image stores for image capture and processing and a full range of software tools for image manipulation. Examples are given of the application of digital image processing techniques to this class of image.

Computers↗

The polar phase response property of monopolar ECG voltages using a Computer-Aided Design and Drafting (CAD)-based data acquisition system.

The present paper discusses a Computer-Aided Design and Drafting (CAD) based data acquisition and polar phase response study of the ECG. The scalar ECG does not show vector properties although such properties are embedded in it. In the present paper the polar phase response property of monopolar chest lead (V1 to V6) ECG voltages has been studied. A software tool has been used to evaluate the relative phase response of ECG voltages. The data acquisition of monopolar ECG records of chest leads V1 to V6 from the chart recorder has been done with the help of the AutoCAD application package. The spin harmonic constituents of ECG voltages are evaluated at each harmonic plane and the polar phase responses are studied at each plane. Some interesting results have been observed in some typical cases which are discussed in the paper.

Algorithms↗

Use of homology domains in sequence similarity detection.

We have found the detection of homology domains using a nonlinear similarity score and the DD algorithm to be a useful approach for identifying similarity between sequences and evaluating potential homology. There are several reasons for the success of the method. (i) Homology domains are identified by a rigorous method that guarantees they will be locally optimal. (ii) The relative significance of different homology domains can be directly compared using the nonlinear similarity score. (iii) Different cost matrices can be used in the calculation of the similarity score. (iv) Relatively long sequences can be compared in a single pass as storage requirements are proportional to the shorter of the two sequences being compared. (v) The method has proved to be very sensitive in practice. (vi) The boundaries of authentic regions of homology are accurately identified. (vii) The information required to define a homology domain (its location, size, similarity score, etc.) can be stored in a compact data structure, facilitating the sharing of homology domain data among different software tools. (viii) The method can be applied to similarity searches of the nucleotide and protein sequence data banks. These properties make the identification of homology domains for studying sequence similarity a useful companion to other accepted methods, such as dynamic programming based analyses.

Animals↗

Hospital comparisons using a Euro Health Data Base for resource management and strategic planning.

A European approach for resource management and strategic planning has been implemented in the HOSCOM project of AIM by defining information standards needed across countries, as well as a methodology to measure resources and costs at the institutional and interinstitutional level. A Euro Health Data Base (EHDB) has been obtained in order to test data availability and comparability as well as to validate models through macrocomparisons using case-mix (DRG's, refined grouping, disease staging) and microcomparisons based on three diseases (cardiac valve replacement, diabetes mellitus and hip fracture). The EHDB's presently based on 274 164 medical record summaries sampled from 7 countries allowed us to build prototypes (using Clipper, Prolog and SQL) in order to export uniform aggregates in the different countries, with standard software tools for statistical comparisons. It showed the present feasibility of using case-mix based on the European Minimum Basic Data Set (MBDS) and the difficulty of obtaining uniform data on resources and costs other than length of stay across countries. Medical data confidentiality was assured but not yet population-based representativity. Given the present state of the EHDB, problems have been clearly identified in order to be solved by international research and development projects in the near future.

Abstracting and Indexing↗

Exercise countermeasure protocol management expert system.

Exercise will be used primarily to countermeasure against deconditioning on extended space flight. In this paper we describe the development and evaluation of an expert system for exercise countermeasure protocol management. Currently, the system includes two major subsystems: baseline prescription and prescription adjustment. The baseline prescription subsystem is designed to provide initial exercise prescriptions while prescription adjustment subsystem is designed to modify the initial prescription based on the exercised progress. The system runs under three different environments: PC, SUN workstation, and Symbolic machine. The inference engine, baseline prescription module, prescription adjustment module and explanation module are developed under the Symbolic environment by using the ART (Automated Reasoning Tool) software. The Sun environment handles database management features and interfaces with PC environment to obtain physical and physiological data from exercise units on-board during the flight. Eight subjects' data have been used to evaluate the system performance by comparing the prescription of nine experienced exercise physiologists and the one prescribed by the expert system. The results of the validation test indicated that the performance of the expert system was acceptable.

Analysis of Variance↗

Measuring irradiated lung and heart area in breast tangential fields using a simulator-based computerized tomography device.

PURPOSE: To illustrate the use of a simulator based computerized tomography system (SIMCT) in the simulation and planning of tangential breast fields. METHODS AND MATERIALS: Forty-five consecutive patients underwent treatment planning using a radiotherapy simulator with computerized tomography attachment. One to three scans were obtained for each patient, calculations were made on the central axis scan. Due to the wide aperture of this system all patients were able to be scanned in the desired treatment position with arm abducted 90 degrees. Using available software tools the area of lung and/or heart included within the tangential fields was calculated. The greatest perpendicular distance (GPD) from the chest wall to posterior field edge was also measured. RESULTS: The mean GPD for the group was 25.40 mm with 71% of patients having GPDs of < or = 30 mm. The mean area of irradiated lung was 1780 sq mm which represented 18.0% of the total ipsilateral lung area seen in the central axis. Seven of the patients with left sided tumors had an average 1314 sq mm heart irradiated in the central axis. This represented 11.9% of total heart area in these patients. CONCLUSIONS: Measurements of irradiated lung and heart area can be easily and accurately made using a SIMCT device. Such measurements may help identify those patients potentially at risk for lung or heart toxicity as a consequence of their treatment. A major advantage of this device is the ability to scan patients in the actual treatment position.

Breast↗

The Mouse Genome Project and human genetics. A report from the 5th International Mouse Genome Mapping Workshop, Lunteren, Holland.

Genome-wide mapping efforts are moving toward the establishment of a 1-cM genetic map of the entire mouse genome. The bulk of linkage groups conserved between the mouse and the human genomes has been identified. Microsatellite mapping has had a major impact on the development of genome-wide genetic maps and, in particular, on genome-wide searches for polygenic disease loci. Some substantial regions of the mouse genome have a marker density of 1 cM or less and many of these regions are now physically mapped. Embryonic YAC contigs have been established in some physically mapped regions. A unitary, global mouse mapping database--the Mouse Genome Database--is under development along with associated software tools. Chromosome committees are having a major impact on the establishment and verification of chromosome maps through the preparation of published annual reports.

Animals↗

Medical decision making based on inductive learning method.

Medical decision making based on inductive learning has been studied in order to collect experience necessary for practical use of such methods in clinical and epidemiological work. The decision trees have been constructed by using the modified Quinlan's approach based on choosing relevant attributes according to their informativity. An inductive learning software tool, ASSISTANT Professional, has been used for experimenting. The variability in results has been studied under varying learning conditions. Two sets of data have been chosen for learning experiments: from a study on rheumatoid factors in patients with rheumatoid arthritis, and from an epidemiological investigation of aging. The results of this study indicate the necessity to determine inductive learning parameters for each particular problem. The pruning procedure is always recommended as it eliminates redundant elements in the tree. In problems with greater number of attributes, however, pruning itself is not guaranteeing satisfactory solutions. Interventions like the change of the minimal weight threshold might improve the situation. If these precautions are met, the method of inductive learning seems to be a useful guide in practical clinical and epidemiological decisions.

Aging↗

Practical 3-D radiotherapy planning of brain tumors.

In postoperative radiotherapy of brain tumors it is usually the case that preoperative imaging studies, either CT or MRI, were performed outside of the purview of the radiation therapy department. Thus the target volume is defined in an imaging study that does not lend itself readily for entry to a 3-D treatment planning system. A method is described that adjusts the patient structure defined by scan data to an appropriate position for radiotherapy. Software tools that are simple to use have been incorporated in a 3-D treatment planning program that allows oblique treatment planes to be defined. The program provides beam's-eye-view plots of the fields that are used to overlay simulation films and will automatically describe a field blocking outline that provides a prescribed margin on the target volume or other structures that have been defined. Finally, dose calculations in arbitrary planes through the head are made and isodose plots produced.

Brain Neoplasms↗

Evaluation of lung MDCT nodule annotation across radiologists and methods.

RATIONALE AND OBJECTIVES: Integral to the mission of the National Institutes of Health-sponsored Lung Imaging Database Consortium is the accurate definition of the spatial location of pulmonary nodules. Because the majority of small lung nodules are not resected, a reference standard from histopathology is generally unavailable. Thus assessing the source of variability in defining the spatial location of lung nodules by expert radiologists using different software tools as an alternative form of truth is necessary. MATERIALS AND METHODS: The relative differences in performance of six radiologists each applying three annotation methods to the task of defining the spatial extent of 23 different lung nodules were evaluated. The variability of radiologists' spatial definitions for a nodule was measured using both volumes and probability maps (p-map). Results were analyzed using a linear mixed-effects model that included nested random effects. RESULTS: Across the combination of all nodules, volume and p-map model parameters were found to be significant at P < .05 for all methods, all radiologists, and all second-order interactions except one. The radiologist and methods variables accounted for 15% and 3.5% of the total p-map variance, respectively, and 40.4% and 31.1% of the total volume variance, respectively. CONCLUSION: Radiologists represent the major source of variance as compared with drawing tools independent of drawing metric used. Although the random noise component is larger for the p-map analysis than for volume estimation, the p-map analysis appears to have more power to detect differences in radiologist-method combinations. The standard deviation of the volume measurement task appears to be proportional to nodule volume.

Artificial Intelligence↗

Application of data mining approaches to drug delivery.

Computational approaches play a key role in all areas of the pharmaceutical industry from data mining, experimental and clinical data capture to pharmacoeconomics and adverse events monitoring. They will likely continue to be indispensable assets along with a growing library of software applications. This is primarily due to the increasingly massive amount of biology, chemistry and clinical data, which is now entering the public domain mainly as a result of NIH and commercially funded projects. We are therefore in need of new methods for mining this mountain of data in order to enable new hypothesis generation. The computational approaches include, but are not limited to, database compilation, quantitative structure activity relationships (QSAR), pharmacophores, network visualization models, decision trees, machine learning algorithms and multidimensional data visualization software that could be used to improve drug delivery after mining public and/or proprietary data. We will discuss some areas of unmet needs in the area of data mining for drug delivery that can be addressed with new software tools or databases of relevance to future pharmaceutical projects.

Computer Simulation↗

Do physicians value decision support? A look at the effect of decision support systems on physician opinion.

OBJECTIVE: Clinical decision support systems are on the verge of becoming routine software tools in clinical settings. We investigate the question of how physicians react when faced with decision support suggestions that contradict their own diagnoses. METHODOLOGY: We used a study design involving 52 volunteer dermatologists who each rated the malignancy of 25 lesion images on an ordinal scale and gave a dichotomous excise/no excise recommendation for each lesion image. After seeing the system's rating and excise suggestions, the physicians could revise their initial recommendations. RESULTS: We observed that in 24% of the cases in which the physicians' diagnoses did not match those of the decision support system, the physicians changed their diagnoses. There was a slight but significant negative correlation between susceptibility to change and experience level of the physicians. Physicians were significantly less likely to follow the decision system's recommendations when they were confident of their initial diagnoses. No differences between the physicians' inclinations to following excise versus no excise recommendations could be observed. CONCLUSION: These results indicate that physicians are quite susceptible to accepting the recommendations of decision support systems, and that quality assurance and validation of such systems is therefore of paramount importance.

Austria↗

Characterization of histone (H1B) oxalate binding protein in experimental urolithiasis and bioinformatics approach to study its oxalate interaction.

The rat kidney H1 oxalate binding protein was isolated and purified. Oxalate binds exclusively with H1B fraction of H1 histone. Oxalate binding activity is inhibited by lysine group modifiers such as 4',4'-diisothiostilbene-2,2-disulfonic acid (DIDS) and pyridoxal phosphate and reduced in presence of ATP and ADP. RNA has no effect on oxalate binding activity of H1B whereas DNA inhibits oxalate binding activity. Equilibrium dialysis method showed that H1B oxalate binding protein has two binding sites for oxalate, one with high affinity, other with low affinity. Histone H1B was modeled in silico using Modeller8v1 software tool since experimental structure is not available. In silico interaction studies predict that histone H1B-oxalate interaction take place through lysine121, lysine139, and leucine68. H1B oxalate binding protein is found to be a promoter of calcium oxalate crystal (CaOx) growth. A 10% increase in the promoting activity is observed in hyperoxaluric rat kidney H1B. Interaction of H1B oxalate binding protein with CaOx crystals favors the formation of intertwined calcium oxalate dehydrate (COD) crystals as studied by light microscopy. Intertwined COD crystals and aggregates of COD crystals were more pronounced in the presence of hyperoxalauric H1B.

Amino Acid Sequence↗

Searching for cancer-associated gene polymorphisms: promises and obstacles.

Low-penetrance genetic variations appear to form the most essential component of the heritability of cancer risk. Search for relevant polymorphic candidates faces significant obstacles, due to both the high number of potentially promising single nucleotide polymorphisms (SNPs) and the intrinsic difficulties in identification of weak gene-disease interactions. At present, extensive case-control studies can be applied only to a limited number of gene polymorphisms. Therefore, the choice of SNPs that deserve an exhaustive populational analysis is of primary importance. Preferences are usually given to those genetic pathways, whose variability and role in cancer causation have been already shown by prior studies. The available electronic databases and software tools may allow further SNP sorting, based on functional predictions. The design for the pilot study may need to be different from the one for large-scale case-control analysis. Some investigations justify non-random patient selection for preliminary assessment of low-penetrance effects, with the emphasis on particularly susceptible individuals (familial, early onset, multiple cancer cases). Other presumably accelerating approaches suggest a decisive exclusion of SNP candidates showing only marginal effects, relaxed formats for rapid dissemination of preliminary data, use of more demonstrative controls such as elderly tumor-free subjects, etc. These short-cuts cannot be properly validated for the time being, due to the paucity of identified low-penetrance risk modifiers. It is expected that the increasing capacities of available DNA collections, coupled with the rapid development of high-throughput genotyping technologies, will vastly accelerate the research on polygenic cancer susceptibility.

Alleles↗

[Image-guided radiotherapy by in-room CT-linear accelerator combination].

Target localization has become increasingly important in the advent of IMRT, as treatment margins are reduced and target doses are increased with high-dose gradients outside this target volume. The in-room CT on rails-LINAC system allows CT imaging while the patient remains immobilized in the treatment position just prior to treatment. The anatomic inter- and intra-fractional variations can be therefore quantified during a course of treatment. The position of the tumour can be checked and corrected before the fraction. In case of modification of tumour shape, a re-planning of the treatment is also feasible. However, several issues remain: the integration with routine clinical treatment due to a lack of software tools, the frequency of imaging, and the cost-efficiency ratio. The clinical experience is yet very limited but CT-image-guided radiotherapy appears promising for prostate, brain and spinal tumours.

Brain Neoplasms↗

Mass spectrometric characterization of peptides derived by peptic cleavage of bovine beta-casein.

This study investigated the digestion of the milk protein beta-casein with pepsin under gastro-analogous conditions. Peptide sequences were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry with post-source decay as well as liquid chromatography-tandem mass spectrometry by means of database searching. The new software tool, Mascot Distiller, improved the identification rate remarkably. In the case of small peptides, such as di- and tri-peptides, which are promising candidates for intestinal absorption and possible biological effects, identification was possible only after spectrum simulation and manual matching. A list of 41 identified peptides having 2-36 amino acids is given, and unexpected cleavage sites for pepsin are reported. Sequence coverage was 75%.

Amino Acid Sequence↗