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In response to the article by R. Leischik et al.: Reproducibility of stress echocardiography using intravenous injection of ultrasound contrast agent (BY963) (see volume 13/5: 387-394)

Many contrast agents will soon be available to the clinicians, but as is evident, contrast echocardiography and the development of agents is still in its infancy. For successful clinical use of contrast echocardiography requires integration of: the development of contrast agents; modifications to ultrasound machines; development and validation of the specific clinical application software.

Analysis of Variance↗

Prediction of arch perimeter changes due to orthodontic treatment.

A borderline orthodontic case with mild to moderate space deficiency can be treated without extractions. Expansion can be used to relieve space deficiency. The prediction of arch perimeter change for a given amount of expansion is helpful in planning the treatment of a patient who needs expansion, and it can facilitate nonextraction orthodontic treatment. To date, different amounts of arch perimeter change have been proposed for the same amount of expansion. A computer program is explained in this study, and examples of its uses are given. By entering 4 parameters of a dental arch into the computer program before and after an orthodontic procedure, one can simply calculate the total and the anterior arch perimeters and see the differences between them numerically and graphically. The program can save, print, change, and delete the calculated data for each patient. For clinicians who do not choose to use the computer program, 2 regression formulas are also presented to calculate the anterior and the total dental arch perimeters. The perimeters of 23 pairs of well-aligned dental arches were measured to check the accuracy of the computer program and the formulas. Paired t tests did not show statistically significant differences between the actual, the computer-derived, and the formula-derived perimeters of the dental arches at 95% confidence level.

Computer Graphics↗

Prediction of exact boundaries of exons.

It is known that while the programs used to predict genes are good at determining coding nucleotides, there are considerable inaccuracies in the determination of the gene structural elements. Among them, the most notable is that of the exact boundaries of exons. In order to assess this, we had earlier reviewed various programs that predict potential splice sites and exons. The results led to the following two observations: (i) a high proportion of false positive splice sites from computational predictions occur in the vicinity of real splice sites; and (ii) current algorithms are misled to predict wrong splice sites more often when the coding potential ends within +/-25 nucleotides from real sites than when it ends at farther positions. In this report, we review decision tree models for human splice sites and the resultant software tool, namely SpliceProximalCheck, that discriminates such'proximal' false positives from real splice sites. Further presented is an integrated system (MZEF-SPC) with Splice ProximalCheck (SPC) as a front-end tool operating on the results of Michael Zhang's exon finder program. Examination of the output of the integrated program on an illustrative gene set revealed that as much as 61 of 93 MZEF-predicted false positive exons could be eliminated by SPC for a loss of only 3 out of 33 MZEF-predicted true positive exons.

Algorithms↗

The Hospital Data Project: comparing hospital activity within Europe.

BACKGROUND: The ability to measure and compare hospital activity between EU member states is important for policy, planning, financing and assessment of population health. Earlier initiatives in this area have been largely directed at standardising high-level indicator definitions without proper account of differences in health systems and health information systems. The Hospital Data Project (HDP) develops a methodology for improved comparability of hospital inpatient and day case activity data across Europe and produces a pilot common data set. All EU members, Iceland and the World Health Organisation are participants. METHODS: The approach comprises a detailed inventory of patient-level hospital data, identification of common areas, specification of data transformations and production of pilot data sets and metadata in a common format. An expert group developed a new diagnosis shortlist based on ICD-10. The project takes account of current work in the area of health care and morbidity indictors and applies the functional specification of health systems developed by the OECD. RESULTS: Seventeen countries have submitted data and metadata in the common format for a single year. Data on inpatients and day cases are classified by age, gender, diagnosis and type of admission. Numbers of hospital discharges, mean and median lengths of stay and population rates are reported. Test data on selected hospital procedures has also been collected. The full data set contains approximately 500,000 records, and software has been designed to facilitate validation and use. CONCLUSION: Results to date are promising. It is a first step in a complex area, and further work is required to extend and refine this approach.

Diagnosis-Related Groups↗

Development of physical and numerical techniques of Alanine/EPR dosimetry in radiotherapy.

In this work, a set of 50 alanine dosimeters has been used in a radiotherapy context, simulating a two-dimensional treatment in a non-overlapping dosimeter configuration. The dose is reconstructed from physical and numerical simulation of the electron paramagnetic resonance signal, calculating the spin density. Thus, it can be used to better adjust the error in the calibration curve to give a final accuracy of <0.03 Gy. A complete set of experimental test parameters have been used with a standard dosimeter in order to obtain the best analysis configuration. These results indicate that for a conventional treatment of some hundreds of mGy, this method can be useful with a correct signal validation. A numerical test and fitting software has been developed. The general use of alanine/electron paramagnetic resonance dosimetry in radiotherapy context is discussed.

Alanine↗

Validation of a new algorithm for the BPM-100 electronic oscillometric office blood pressure monitor.

BACKGROUND: To test the accuracy of a new algorithm for the BPM-100, an automated oscillometric blood pressure (BP) monitor, using stored data from an independently conducted validation trial comparing the BPM-100(Beta) with a mercury sphygmomanometer. DESIGN: Raw pulse wave and cuff pressure data were stored electronically using embedded software in the BPM-100(Beta), during the validation trial. The 391 sets of measurements were separated objectively into two subsets. A subset of 136 measurements was used to develop a new algorithm to enhance the accuracy of the device when reading higher systolic pressures. The larger subset of 255 measurements (three readings for 85 subjects) was used as test data to validate the accuracy of the new algorithm. METHODS: Differences between the new algorithm BPM-100 and the reference (mean of two observers) were determined and expressed as the mean difference +/- SD, plus the percentage of measurements within 5, 10, and 15 mmHg. RESULTS: The mean difference between the BPM-100 and reference systolic BP was -0.16 +/- 5.13 mmHg, with 73.7% < or = 5 mmHg, 94.9% < or = 10 mmHg and 98.8% < or = 15 mmHg. The mean difference between the BPM-100 and reference diastolic BP was -1.41 +/- 4.67 mmHg, with 78.4% < or = 5 mmHg, 92.5% < or = 10 mmHg, and 99.2% < or = 15 mmHg. These data improve upon that of the BPM-100(Beta) and pass the AAMI standard, and 'A' grade BHS protocol. CONCLUSION: This study illustrates a new method for developing and testing a change in an algorithm for an oscillometric BP monitor utilizing collected and stored electronic data and demonstrates that the new algorithm meets the AAMI standard and BHS protocol.

Adolescent↗

Safety of computer-assisted surgery for cannulated hip screws.

Computer-assisted orthopaedic surgery has developed considerably during the past few years. Several manufacturers produce hardware and software for use in trauma surgery. Validation of these systems before clinical application is mandatory to be sure they work accurately and safely. The accuracy of surgical performance is highly correlated with the cut-out percentages of hip screws. In a standardized operative setting, three cannulated hip screws were inserted in each of 20 sawbones. The screws were positioned either by fluoroscopic navigation technique or by conventional operative technique depending on randomization. Our primary aim was to assess whether computer-navigated screw fixation is equally safe compared with conventional screw fixation using fluoroscopy. To determine safety, we investigated number of drilling attempts, screw position, and radiation time. Secondary to these safety parameters, we also compared the operating time between the two procedures to assess the efficiency of computer navigation. Statistical analysis showed no differences regarding accuracy of screw position. Computer-assisted surgery resulted in fewer drilling attempts and less radiation time, with a similar operation time. We believe the currently used navigation system is safe and accurate.

Bone Screws↗

MUMBO: a protein-design approach to crystallographic model building and refinement.

In recent years, significant progress has been achieved in automation of the crystal structure-determination process. However, the final part of this process, namely the refinement of the atomic model, is still tedious for biological macromolecules because, especially at lower resolution, it requires extensive manual intervention. Here, it is shown that computer algorithms widely used in protein-design approaches can substantially simplify this process, helping to identify the correct orientation of the side chains during refinement. This approach was implemented into the computer program MUMBO. As in many protein-design programs, side-chain rotamer diversity is generated using rotamer libraries. The selection of the best combination of side-chain orientations is based on either the dead-end elimination (DEE) theorem or a Metropolis Monte Carlo approach and on a detailed atomic scoring function that describes the molecular interactions between the rotamers. We show that this scoring function can be easily extended and complemented through the introduction of an X-ray pseudo-energy calculated from the electron density present at the position of the rotamer. This extension is fully compatible with present protein-design algorithms and it is shown for a number of test cases that using this approach model refinement is simplified and convergence occurs faster.

Algorithms↗

Neonatal malaria in Nigeria--a 2 year review.

BACKGROUND: In view of the fact that a significant proportion of neonates with malaria may be missed on our wards on the assumption that the disease condition is rare, this study aims at documenting the prevalence of malaria in neonates admitted into our neonatal ward. Specifically, we hope to describe its clinical features and outcome of this illness. Knowledge of these may ensure early diagnosis and institution of prompt management. METHODS: Methods Hospital records of all patients (two hundred and thirty) admitted into the Neonatal ward of Olabisi Onabanjo University Teaching Hospital, Sagamu between 1st January 1998 and 31st December 1999 were reviewed. All neonates (fifty-seven) who had a positive blood smear for the malaria parasite were included in the study. Socio-demographic data as well as clinical correlates of each of the patients were reviewed. The Epi-Info 6 statistical software was used for data entry, validation and analysis. A frequency distribution was generated for categorical variables. To test for an association between categorical variables, the chi-square test was used. The level of significance was put at values less than 5%. RESULTS: Prevalence of neonatal malaria in this study was 24.8% and 17.4% for congenital malaria. While the mean duration of illness was 3.60 days, it varied from 5.14 days in those that died and and 3.55 in those that survived respectively. The duration of illness significantly affected the outcome (p value = 0.03). Fever alone was the clinical presentation in 44 (77.4%) of the patients. Maturity of the baby, sex and age did not significantly affect infestation. However, history of malaria/febrile illness within the 2 weeks preceding the delivery was present in 61.2% of the mothers. Maternal age, concurrent infection and duration of illness all significantly affected the outcome of illness. Forty-two (73.7%) of the babies were discharged home in satisfactory condition. CONCLUSION: It was concluded that taking a blood smear to check for the presence of the malaria parasite should be included as part of routine workup for all neonates with fever or those whose mothers have history of fever two weeks prior to delivery. In addition, health education of pregnant mothers in the antenatal clinic should include early care-seeking for newborns.

Adolescent↗

The tissue microarray data exchange specification: a community-based, open source tool for sharing tissue microarray data.

BACKGROUND: Tissue Microarrays (TMAs) allow researchers to examine hundreds of small tissue samples on a single glass slide. The information held in a single TMA slide may easily involve Gigabytes of data. To benefit from TMA technology, the scientific community needs an open source TMA data exchange specification that will convey all of the data in a TMA experiment in a format that is understandable to both humans and computers. A data exchange specification for TMAs allows researchers to submit their data to journals and to public data repositories and to share or merge data from different laboratories. In May 2001, the Association of Pathology Informatics (API) hosted the first in a series of four workshops, co-sponsored by the National Cancer Institute, to develop an open, community-supported TMA data exchange specification. METHODS: A draft tissue microarray data exchange specification was developed through workshop meetings. The first workshop confirmed community support for the effort and urged the creation of an open XML-based specification. This was to evolve in steps with approval for each step coming from the stakeholders in the user community during open workshops. By the fourth workshop, held October, 2002, a set of Common Data Elements (CDEs) was established as well as a basic strategy for organizing TMA data in self-describing XML documents. RESULTS: The TMA data exchange specification is a well-formed XML document with four required sections: 1) Header, containing the specification Dublin Core identifiers, 2) Block, describing the paraffin-embedded array of tissues, 3)Slide, describing the glass slides produced from the Block, and 4) Core, containing all data related to the individual tissue samples contained in the array. Eighty CDEs, conforming to the ISO-11179 specification for data elements constitute XML tags used in the TMA data exchange specification. A set of six simple semantic rules describe the complete data exchange specification. Anyone using the data exchange specification can validate their TMA files using a software implementation written in Perl and distributed as a supplemental file with this publication. CONCLUSION: The TMA data exchange specification is now available in a draft form with community-approved Common Data Elements and a community-approved general file format and data structure. The specification can be freely used by the scientific community. Efforts sponsored by the Association for Pathology Informatics to refine the draft TMA data exchange specification are expected to continue for at least two more years. The interested public is invited to participate in these open efforts. Information on future workshops will be posted at http://www.pathologyinformatics.org (API we site).

Community Health Services↗

Spatial distribution of nymphs of Scaphoideus titanus (Homoptera: Cicadellidae) in grapes, and evaluation of sequential sampling plans.

The spatial distribution of the nymphs of Scaphoideus titanus Ball (Homoptera Cicadellidae), the vector of grapevine flavescence dorée (Candidatus Phytoplasma vitis, 16Sr-V), was studied by applying Taylor's power law. Studies were conducted from 2002 to 2005, in organic and conventional vineyards of Piedmont, northern Italy. Minimum sample size and fixed precision level stop lines were calculated to develop appropriate sampling plans. Model validation was performed, using independent field data, by means of Resampling Validation of Sample Plans (RVSP) resampling software. The nymphal distribution, analyzed via Taylor's power law, was aggregated, with b = 1.49. A sample of 32 plants was adequate at low pest densities with a precision level of D0 = 0.30; but for a more accurate estimate (D0 = 0.10), the required sample size needs to be 292 plants. Green's fixed precision level stop lines seem to be more suitable for field sampling: RVSP simulations of this sampling plan showed precision levels very close to the desired levels. However, at a prefixed precision level of 0.10, sampling would become too time-consuming, whereas a precision level of 0.25 is easily achievable. How these results could influence the correct application of the compulsory control of S. titanus and Flavescence dorée in Italy is discussed.

Animals↗

Building a Web-based drug ordering system for hospitals: from requirements engineering to prototyping.

Web-based drug ordering allows a growing number of hospitals without pharmacy to communicate seamlessly with their external pharmacy. Business process analysis and object oriented modelling performed together with the users at a pilot hospital resulted in a comprehensive picture of the user and business requirements for electronic drug ordering. The user requirements were further validated with the help of a software prototype. In order to capture the needs of a large number of users CAP10, a new method making use of pre-built models, is proposed. Solutions for coping with the technical requirements (interfacing the business software at the pharmacy) and with the legal requirements (signing the orders) are presented.

Computer Simulation↗

Evaluating the web as a clinical knowledge base.

Medical diagnostic decision support systems are some of the most visible applications of medical informatics. Many of these systems, however, were created in the pre-WWW era, when access to clinical knowledge was much more limited than it is currently. Using the Google(tm) Java API1, we created a simple program to extract potential diagnoses from a general web search. Our system performed at a level comparable to other medical expert systems.

Algorithms↗

Solid phase cytometry for detection of rare events.

We describe a simple and rapid laser scanning device for solid phase cytometry. This system can detect and count fluorescent cells over a 22 mm diameter surface (membrane or glass circle) as well as quantify the fluorescence that they emit. A comprehensive discrimination package includes optical and software parameters and accurately distinguishes between valid signals (e.g., labelled cells) and nonspecific signals (e.g., auto-fluorescent particles and debris). Any event detected may also be easily confirmed by visual observation after transfer of the sample to an epifluorescence microscope fitted with a motorized stage driven by the system. We show a linear relationship between the amount of fluorescein coupled to the cells and the fluorescence signal of the cells detected. This approach is not destructive and further characterization of the sample may be carried out. We have been able to detect rare cellular events at a frequency of 10(-7) in 3 min. Potential applications include monitoring of residual disease in oncology and detection of virus-infected cells circulating at very low frequencies.

Animals↗

Ovarian cancer identification based on dimensionality reduction for high-throughput mass spectrometry data.

MOTIVATION: High-throughput and high-resolution mass spectrometry instruments are increasingly used for disease classification and therapeutic guidance. However, the analysis of immense amount of data poses considerable challenges. We have therefore developed a novel method for dimensionality reduction and tested on a published ovarian high-resolution SELDI-TOF dataset. RESULTS: We have developed a four-step strategy for data preprocessing based on: (1) binning, (2) Kolmogorov-Smirnov test, (3) restriction of coefficient of variation and (4) wavelet analysis. Subsequently, support vector machines were used for classification. The developed method achieves an average sensitivity of 97.38% (sd = 0.0125) and an average specificity of 93.30% (sd = 0.0174) in 1000 independent k-fold cross-validations, where k = 2, ..., 10. AVAILABILITY: The software is available for academic and non-commercial institutions.

Algorithms↗

eHiTS: a new fast, exhaustive flexible ligand docking system.

The flexible ligand docking problem is divided into two subproblems: pose/conformation search and scoring function. For successful virtual screening the search algorithm must be fast and able to find the optimal binding pose and conformation of the ligand. Statistical analysis of experimental data of bound ligand conformations is presented with conclusions about the sampling requirements for docking algorithms. eHiTS is an exhaustive flexible-docking method that systematically covers the part of the conformational and positional search space that avoids severe steric clashes, producing highly accurate docking poses at a speed practical for virtual high-throughput screening. The customizable scoring function of eHiTS combines novel terms (based on local surface point contact evaluation) with traditional empirical and statistical approaches. Validation results of eHiTS are presented and compared to three other docking software on a set of 91 PDB structures that are common to the validation sets published for the other programs.

Algorithms↗

Meta-DiSc: a software for meta-analysis of test accuracy data.

BACKGROUND: Systematic reviews and meta-analyses of test accuracy studies are increasingly being recognised as central in guiding clinical practice. However, there is currently no dedicated and comprehensive software for meta-analysis of diagnostic data. In this article, we present Meta-DiSc, a Windows-based, user-friendly, freely available (for academic use) software that we have developed, piloted, and validated to perform diagnostic meta-analysis. RESULTS: Meta-DiSc a) allows exploration of heterogeneity, with a variety of statistics including chi-square, I-squared and Spearman correlation tests, b) implements meta-regression techniques to explore the relationships between study characteristics and accuracy estimates, c) performs statistical pooling of sensitivities, specificities, likelihood ratios and diagnostic odds ratios using fixed and random effects models, both overall and in subgroups and d) produces high quality figures, including forest plots and summary receiver operating characteristic curves that can be exported for use in manuscripts for publication. All computational algorithms have been validated through comparison with different statistical tools and published meta-analyses. Meta-DiSc has a Graphical User Interface with roll-down menus, dialog boxes, and online help facilities. CONCLUSION: Meta-DiSc is a comprehensive and dedicated test accuracy meta-analysis software. It has already been used and cited in several meta-analyses published in high-ranking journals. The software is publicly available at http://www.hrc.es/investigacion/metadisc_en.htm.

Clinical Laboratory Techniques↗