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Voxeldoes: a computer program for 3-D dose calculation in therapeutic nuclear medicine.

A computer program, VoxelDose, was developed to calculate patient specific 3-D-dose maps at the voxel level. The 3-D dose map is derived in three steps: (i) The SPECT acquisitions are reconstructed using a filtered back projection method, with correction for attenuation and scatter; (ii) the 3-D cumulated activity map is generated by integrating the SPECT data; and (iii) a 3-D dose map is computed by convolution (using the Fourier Transform) of the cumulated activity map and corresponding MIRD voxel S values. To validate the VoxelDose software, a Liqui-Phil abdominal phantom with four simulated organ inserts and one spherical tumor (radius 4.2 cm) was filled with known activity concentrations of 111In. Four cylindrical calibration tubes (from 3.7 to 102 kBq/mL) were placed on the phantom. Thermoluminescent mini-dosimeters (mini-TLDs) were positioned on the surface of the organ inserts. Percent differences between the known and measured activity concentrations were determined to be 12.1 (tumor), 1.8 (spleen), 1.4, 8.1 (right and left kidneys), and 38.2% (liver), leading to percent differences between the calculated and TLD measured doses of 41, 16, 3, 5, and 62%. Large differences between the measured and calculated dose in the tumor and the liver may be attributed to several reasons, such as the difficulty in precisely associating the position of the TLD to a voxel and limits of the quantification method (mainly the scatter correction and partial volume effect). Further investigations should be performed to better understand the impact of each effect on the results and to improve absolute quantification. For all other organs, activity concentration measurements and dose calculations agree well with the known activity concentrations.

Humans↗

Using pooled exposure assessment to improve efficiency in case-control studies.

Assays can be so expensive that interesting hypotheses become impractical to study epidemiologically. One need not, however, perform an assay for everyone providing a biological specimen. We propose pooling equal-volume aliquots from randomly grouped sets of cases and randomly grouped sets of controls, and then assaying the smaller number of pooled samples. If an effect modifier is of concern, the pooling can be done within strata defined by that variable. For covariates assessed on individuals (e.g., questionnaire data), set-based counterparts are calculated by adding the values for the individuals in each set. The pooling set then becomes the unit of statistical analysis. We show that, with appropriate specification of a set-based logistic model, standard software yields a valid estimated exposure odds ratio, provided the multiplicative formulation is correct. Pooling minimizes the depletion of irreplaceable biological specimens and can enable additional exposures to be studied economically. Statistical power suffers very little compared with the usual, individual-based analysis. In settings where high assay costs constrain the number of people an investigator can afford to study, specimen pooling can make it possible to study more people and hence improve the study's statistical power with no increase in cost.

Animals↗

[Bayesian statistics-based method for genetic linkage analysis].

Bayesian School as one of the important statistical schools is different from the Classical Statistics, and the Bayesian methods have been widely used in many fields of modern sciences. In the present paper, we discussed the application of Bayesian method in linkage analysis, including the Bayesian estimation of recombination fraction, linkage testing based on the Bayes Factor and the Bayesian approach for genetic linkage map construction via Markov chain Monte Carlo algorithm. Simulation study and real data analysis were performed using SAS/IML software, and the validity and practicability of Bayesian method in genetic linkage analysis were thus verified.

Bayes Theorem↗

Sirolimus population pharmacokinetic/pharmacogenetic analysis and bayesian modelling in kidney transplant recipients.

OBJECTIVES: The objectives of the present study were: (i) to analyse the population pharmacokinetics of sirolimus in renal transplant recipients co-administered mycophenolate mofetil, but no calcineurin inhibitor over the first 3 months post-transplantation and study the influence of different potential covariates, including genetic polymorphisms of cytochrome P450 (CYP) metabolic enzymes and active transporters, on pharmacokinetic parameters; and (ii) to develop a Bayesian estimator able to reliably estimate the individual pharmacokinetic parameters and exposure indices in this population. METHODS: Twenty-two adult renal transplant patients treated with sirolimus participated in this study. Ninety concentration-time profiles (938 sirolimus whole blood samples) were collected at days 7 and 14, and months 1 and 3 post-transplantation. The population pharmacokinetic study was conducted using the nonlinear mixed effects model software, NONMEM, and validated using both the bootstrap and the cross-validation approaches. Finally, a Bayesian estimator based on a limited sampling strategy was built using the post hoc option. RESULTS: A two-compartment open model with first-order elimination and Erlang's distribution (to describe the absorption phase) best fitted the data. The mean pharmacokinetic parameter estimates were 5.25 h(-1), 218L and 292L for the transfer rate constant, the apparent volume of the central and peripheral compartments, respectively. The CYP3A5*1/*3 polymorphism significantly influenced the apparent oral clearance: mean oral clearance = 14.1 L/h for CYP3A5 non expressers (CYP3A5*3/*3 genotype) versus 28.3 L/h for CYP3A5 expressers (CYP3A5*1/*3 and *1/*1 genotypes). The standard errors of all the parameter estimates were <15%. Maximum a posteriori Bayesian forecasting allowed accurate prediction of sirolimus area under the concentration-time curve from 0 to 24 hours using a combination of only three sampling times (0, 1 and 3 hours post-dose), with a non-significant bias of -2.1% (range -22.2% to +25.9%), and a good precision (root mean square error = 10.3%). This combination is also easy to implement in clinical practice. CONCLUSION: This study presents an accurate population pharmacokinetic model showing the significant influence of the CYP3A5*1/*3 polymorphism on sirolimus apparent oral clearance, and a Bayesian estimator accurately predicting sirolimus pharmacokinetics in patients co-administered mycophenolate mofetil, but no calcineurin inhibitor.

Adult↗

Respiratory function testing in early childhood: where have we come from and where are we going?

After an initially slow beginning, we are currently witnessing something of a revolution in the field of respiratory function testing during early childhood, both with respect to the number of techniques available and the applications to which they are being put. There is now an urgent need for international, collaborative efforts to develop more objective, standardized methods of assessment (including improved, properly validated equipment and software) and reliable reference data for this age group. This would improve our understanding of exactly what these tests are measuring, and facilitate the development of effective therapeutic and preventive strategies to minimize suffering from respiratory illness not only during early childhood but, hopefully, throughout life.

Child, Preschool↗

Clinical terminology: why is it so hard?

Despite years of work, no re-usable clinical terminology has yet been demonstrated in widespread use. This paper puts forward ten reasons why developing such terminologies is hard. All stem from underestimating the change entailed in using terminology in software for 'patient centred' systems rather than for its traditional functions of statistical and financial reporting. Firstly, the increase in scale and complexity are enormous. Secondly, the resulting scale exceeds what can be managed manually with the rigour required by software, but building appropriate rigorous representations on the necessary scale is, in itself, a hard problem. Thirdly, 'clinical pragmatics'--practical data entry, presentation and retrieval for clinical tasks--must be taken into account, so that the intrinsic differences between the needs of users and the needs of software are addressed. This implies that validation of clinical terminologies must include validation in use as implemented in software.

Medical Informatics↗

[Study on the distribution of malaria in Hainan province through spatial local interpolation technique].

OBJECTIVE: To explore the spatial distribution of malaria in Hainan province. METHODS: Maps of spatial distribution on malaria incidence in Hainan province from 1995 to 1999 were produced, using a spatial local interpolation technique in the ArcGIS 8.1 software. Cross-validation techniques were used to evaluate the fitness of the distribution maps. RESULTS: The spatial distribution of malaria in Hainan province from 1995 to 1999 showed that the incidence of malaria in the southern part of Hainan province were higher than that in the north. In the south, the incidence of malaria in east coastal areas were higher than that of other parts, especially in Wuzhi and Yingge mountains. The prediction error of the cross-validation indicated that the spatial distribution maps of malaria in Hainan had good fitness of malaria incidence of Hainan province. CONCLUSION: Spatial local interpolation technique seemed to be promising in describing the spatial distribution of malaria.

Adult↗

[Cytostatic prescription errors: an analysis of causes, and proposals regarding their prevention].

OBJECTIVE: To collect and analyze prescription errors for parenterally-administered cytostatic drugs, to identify causes from results obtained, and to suggest feasible solutions to prevent them. METHOD: In our hospital, parenterally-administered cytotoxic drugs are prepared in the Pharmacy Department, where 100% of prescriptions are validated with the help of a software program. Prescription errors detected at validation over a 2-year period of time were recorded in a specific form to facilitate analysis. RESULTS: In all, 292 possible errors were detected and 183 were confirmed; most resulted from dosing errors, followed by incorrect treatment duration. Other errors detected included: dose or drug omitted, wrong administration route, wrong patient, and wrong medication. The following measures were suggested: improvement of the data processing system at the Pharmacy Department, implementation of an electronic prescription system, continuous updating of cytostatic therapy protocols, and inclusion of cytostatic prescription recommendations within Pharmacotherapeutic Guidelines. CONCLUSION: Most common errors included doses above or below the correct ones, with the primary cause being poor handwriting in manual prescriptions. Active recording of prescription errors is essential if an analysis of real causes in our setting is to be undertaken, as well as to making proposals and implementing definite solutions.

Antineoplastic Agents↗

Validity of scores generated by a web-based multimedia simulated patient case software: a pilot study.

PURPOSE: The value of multimedia simulated patient cases (MSPCs) in medical education remains unclear. The authors conducted a pilot study to assess the validity of automated scores of diagnostic reasoning ability provided by DxR Clinician, a widely available Web-based MSPC software. METHOD: In 2002-03, all 89 students enrolled in a required third-year primary care clerkship at the University of California, Davis, School of Medicine were assigned to complete four MSPCs. The authors determined the degree of correlation between the Clinical Reasoning Score (CRS) and Level of Diagnostic Performance (LDP) generated by the MSPC software and subscale scores from a validated measure of diagnostic reasoning sophistication, the Diagnostic Thinking Inventory (DTI). RESULTS: Of 356 completed case events, instructor override of automated scoring was required in 206 (58%) to obtain an accurate LDP and CRS. Mean DTI subscale scores improved significantly from the beginning to the end of the year (p <.0001, Wilcoxon signed rank test). However, there were no significant correlations between CRS or LDP scores on any of the four cases and either of the two DTI subscale scores. CONCLUSION: Automated diagnostic reasoning scores generated by one widely available MSPC software appear to lack criterion validity. The validity of automated diagnostic reasoning scores generated by MSPCs should be established before such cases can be confidently employed as educational tools.

Clinical Clerkship↗

Automated and accurate deposition of structures solved by X-ray diffraction to the Protein Data Bank.

The RCSB Protein Data Bank (PDB) has a number of options for deposition of structural data and has developed software tools to facilitate the process. In addition to ADIT and the PDB Validation Suite, a new software application, pdb_extract, has been designed to promote automatic data deposition of structures solved by X-ray diffraction. The pdb_extract software can extract information about data reduction, phasing, molecular replacement, density modification and refinement from the output files produced by many X-ray crystallographic applications. The options, procedures and tools for accurate and automated PDB data deposition are described here.

Automation↗

An interinstitutional comparative study and validation of computer aided drusen quantification.

AIMS: To assess the portability and clinical applicability of a software program based on Photoshop (Adobe Systems Inc, San Jose, CA, USA) for digital drusen quantification. METHODS: Independent graders from the Digital Fundus Photo Reading Center of Columbia University and King's College Hospital used macular background levelling software to quantify the percentage of drusen in the central and middle Wisconsin subfields. 100 images of consecutive patients with choroidal neovascularisation in one eye and significant drusen in the other eye were analysed to determine suitability, and 10 were chosen for assessment by this software. RESULTS: Of the 10 images used in the interinstitutional validation, the random effects ANOVA for the central and middle subfields showed a high degree of interobserver agreement. The ICC for interobserver reliability was 0.83 (95% CI: 67 to 95) for the central subfield and 0.84 (95% CI: 69 to 99) for the middle subfield. Overall agreement with the manual grading results was good and the within patient coefficient of variation was about 20% for all the pairwise comparisons between observers and the manual stereo gradings. Of the 100 images used to assess practical applicability of the software, 79 were suitable for semiautomated analysis. 13 had extensive mixed retinal pigment epithelial (RPE) changes limiting drusen identification, five had a significant number of reticular drusen, which are poorly identified by the software, and three had multiple small areas of RPE atrophy, which are difficult to distinguish from drusen. CONCLUSIONS: The software was successfully used by two institutions demonstrating portability, with good correlation between graders and to the manual stereo grading. Digital drusen quantification was possible in 79% of the images analysed.

Analysis of Variance↗

Development of a computer software for easy storage and analysis of fibreoptic bronchoscopy data.

OBJECTIVE: To develop a simple software for management of fibreoptic bronchoscopy records. METHODS: After identification of the specific needs at our hospital, a software was developed. A graphical interface with structured data entry related to patient information and diagnosis, bronchoscopic findings and specimens obtained, and their reports were envisaged. After initial construction, the software was tested over a four-week period. The software was put to routine use after necessary corrections, and validated over the next few months through actual data entry. RESULTS: The software has various modules for input and modification of data, as well as for generation of reports, and can work both on stand-alone personal computers and on networks. With little practice, residents soon became adept at entering details correctly and quickly. The slightly increased time of data entry into the computer was more than made up by uniform and complete report generation. The database component was evaluated by analyzing 1000 consecutive records entered over a 14-month period, and no discrepancies were observed. CONCLUSION: A user-friendly software providing uniform and complete data entry regarding fibreoptic bronchoscopic procedures was developed.

Bronchoscopy↗

Manual verification of computer analysis of 24-hour esophageal motility.

The application of solid-state technology to intraesophageal pressure monitoring over an entire circadian cycle has resulted in large amounts of data that require computer analysis. Recently available commercial software has yet to be validated. The aim of this study was to compare the analysis of ambulatory esophageal manometry by an automated computer program with manual analysis and make the software modifications necessary to validate the automated system for clinical use. Computer-aided analysis of a large number of esophageal contractions recorded during ambulatory esophageal manometry was compared with manual analysis by four experienced physicians. Good correlations were found between manual and computerized measurements of contraction amplitude and duration (r = 0.99 and r = 0.73, respectively). Software modifications resulted in correct identification of 94% of contractions and correct classification of 93.3% of these waves as peristaltic or simultaneous. These results demonstrate that the evaluated program for automated analysis of ambulatory esophageal manometry is accurate and reliable for research and clinical applications.

Circadian Rhythm↗

Development of a novel CASA system based on open source software for characterization of zebrafish sperm motility parameters.

Although computer-assisted sperm analysis (CASA) outperforms manual techniques, many investigators rely on non-automated analysis due to the high cost of commercial options. In this study, we have written and validated a free CASA software primarily for analysis of fish sperm. This software is a plugin for the free National Institutes of Health software ImageJ and is available with documentation at . That it is open source makes possible external validation, should improve quality control and enhance the comparative value of data obtained among laboratories. In addition, we have improved upon the traditional velocity straight line (VSL) algorithm, eliminating inaccurate characterization of highly curved fish sperm paths. Using this system, the motion of zebrafish (Danio rerio) sperm was characterized relative to time post-activation and the impact of acquisition conditions upon data analysis determined. There were decreases in velocity and path straightness (STR), but not linearity (LIN), relative to time. From 30 to 300 frames/s, frame rate significantly affected curvilinear velocity (VCL) and STR measurements. Sperm density in the field of view did not affect any measured parameter. There was significant inter-male variation for VCL, VSL, velocity average path (VAP), percent motility, path character (STR, LIN), and duration of motility. Furthermore, relative sperm output (a measure reflecting both semen volume and concentration) was positively correlated to percent motility. For all motion parameters measured (except duration), the average CV was < or =10%, comparable to values obtained using commercial systems.

Algorithms↗

Clinical validation of the gated blood pool SPECT QBS processing software in congestive heart failure patients: correlation with MUGA, first-pass RNV and 2D-echocardiography.

INTRODUCTION: Left (LVEF) and right ventricular ejection fraction (RVEF) as well as LV regional wall motion at rest are valuable tools to monitor and tailor treatment of congestive heart failure (CHF) patients. Gated blood pool SPECT (GBPS) is under evaluation as an "all-in-one" technique, providing information on LVEF, RVEF, and wall motion derived from a single examination. Aim of the study was to evaluate a commercially available automated GBPS processing software for EF measurements and wall motion analysis in heart failure patients. METHODS: Thirty-two patients (12 female; mean age+/-SD: 53+/-13 years), suffering from dilated (63%), ischemic (25%) or hypertrophic (13%) cardiomyopathy, were studied. First-pass radionuclide ventriculography (FP-RNV), planar multigated radionuclide angiography (MUGA), and GBPS were performed at rest after in vivo labeling of red blood cells, and LVEF and RVEF was calculated with each method. Later on the same day LVEF was calculated by echocardiography. LV wall motion (summed motion score and wall motion index) was derived from GBPS and echocardiography using the standard 16-segment model. RESULTS: Mean LVEF measured by GBPS, echocardiography, MUGA and FP-RNV was 33+/-13%, 37+/-15%, 41+/-14% and 45+/-13%, respectively. LVEF values calculated from GBPS showed moderate to good correlation with FP-RNV (r=0.61), MUGA (r=0.65) and ECHO (r=0.74; all p<0.01). Mean RVEF calculated by GBPS, FP-RNV and MUGA was 45+/-14%, 46+/-9% and 38+/-9%, respectively. RVEF values calculated from GBPS showed weak correlation with FP-RNV (r=0.33) and MUGA (r=0.26; all p=n.s.). Assessment of GBPS wall motion was qualitatively possible in all patients. The agreement between GBPS and ECHO was 82% (kappa=0.73). The wall motion index showed good correlation between both methods (r=0.88; p<0.001). CONCLUSION: An automated algorithm for LVEF calculation and wall motion analysis using GBPS is feasible for clinical routine diagnostic in CHF patients. The RVEF calculation method needs to be improved before routine clinical application can be recommended.

Algorithms↗

The validity of the prediction of Soft Tissue profile changes after LeFort I osteotomy using the dentofacial planner (computer software).

The purpose of this study was to examine the validity of the prediction of soft tissue changes after LeFort I osteotomy with the DentoFacial Planner (DFP) (computer software). The preoperative and postoperative lateral cephalograms of 21 white adult orthodontic patients (10 males and 11 females) who underwent only LeFort I osteotomy as part of their overall treatment were digitized. A coordinate system of X and Y axes were used to assess the amount and direction of movement of the maxilla. The SN + 7 degrees was the X axis, and a perpendicular to this plane from nasion was the Y axis. The sample was divided into two groups depending on the amount of forward movement of the maxilla. More than 2 mm of anterior placement of the maxilla comprised the advancement group (13 patients) and less than 2 mm comprised the impaction group (8 patients). The selection criteria for the sample were (1) before and after cephalograms taken with lips in repose and in centric occlusion; (2) all preoperative records taken almost immediately before surgery; (3) postoperative records taken at least 6 months after surgery and checked by regional superimposition of the preoperative and postoperative lateral cephalograms onto the maxilla and the mandible. No tooth movement occurred between the time the records were taken. The following soft tissue landmarks were examined: pronasale, subnasale, stomion superior, middle upper lip, stomion inferior, middle lower lip, labrale inferior, labiomental fold, and pogonion. The results indicate that for some of these landmarks the amount and direction of soft tissue changes differed between the DFP prediction and the actual surgical changes by LeFort I osteotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Software for quantification of labeled bacteria from digital microscope images by automated image analysis.

Automated image analysis software, CellC, was developed and validated for quantification of bacterial cells from digital microscope images. CellC enables automated enumeration of bacterial cells, comparison of total count and specific count images [e.g., 4',6-diamino-2-phenylindole (DAPI) and fluorescence in situ hybridization (FISH) images], and provides quantitative estimates of cell morphology. The software includes an intuitive graphical user interface that enables easy usage as well as sequential analysis of multiple images without user intervention. Validation of enumeration reveals correlation to be better than 0.98 when total bacterial counts by CellC are compared with manual enumeration, with all validated image types. The software is freely available and modifiable: the executable files and MATLAB source codes can be obtained at www. cs. tut.fi/sgn/csb/cellc.

Bioreactors↗

The analysis of heart rate variability in unrestrained rats. Validation of method and results.

An experimental setting and software were developed to evaluate cardiac autonomic function in unrestrained rats. Subcutaneously implanted ECG electrodes and an indwelling venous catheter were tunneled to a tail cuff in five rats. The ECG was A/D converted at 1000 Hz. After peak detection, a time series of RR intervals was obtained. Programs for the analysis of heart rate variability (HRV) were implemented in LabVIEW. Statistical properties were determined in the time domain. After cubic spline function curve fitting, resampling at 0.1 s and test for stationarity, power spectral analysis was performed on sampled records of 30 min duration after applying a sliding Hanning window (Welch method: 256 points (duration 25.6 s), 50% overlap and 0.039 Hz resolution). Algorithms were tested with simulated signals consisting of isolated frequency components, which were retrieved at their exact locations. Physiological validation of the system was performed by, beta-adrenergic and cholinergic blockade and by forced breathing at a fixed rate. Measurements were performed on five unrestrained rats under basal conditions. Mean RR was 174.2 +/- 3.6 ms; S.D., 13.3 +/- 4.6 ms; rMSSD, 5.2 + /- 1.2 ms; pNN10, 3.5 +/- 1.9% and pNN5, 18.7 +/- 6.4%. Low (0.19-0.74 Hz) and high frequency (0.78-2.5 Hz) power were determined (and also percent of low to total and high to total): 18.42 +/- 10.74 ms2 (22.9 +/- 6.5%) and 15.66 +/- 5.56 ms2 (19.9 +/- 2.7%), and the ratio low/high: 1.16 +/- 0.39. In conclusion, HRV analysis programs were developed and thoroughly tested through simulations and in vivo, under basal conditions and after pharmacological blockades. Using this software, HRV data from unrestrained rats were obtained.

Animals↗