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Differential leukocyte counts determined in chicken blood using the Cell-Dyn 3500.

BACKGROUND: Automated hematology instruments commonly are used for mammalian blood analysis, but there is a lack of accurate automated methods available for avian leukocyte analysis. OBJECTIVE: The aim of this study was to validate differential leukocyte counts in blood from chickens using the Cell-Dyn 3500 hematology system and avian-specific software. METHODS: Blood samples were collected in lithium-heparin tubes from 2 groups (n = 84 and n = 139) of laying hens. Manual 200-cell differential counts were done on routinely-stained blood smears, and manual total granulocyte counts (heterophils and eosinophils) were done using an eosinophil stain in a counting chamber. Automated differential counts were done using VET 2.3, a research and development version of avian-specific software for the Cell-Dyn 3500. Results were analyzed using Pearson's correlation and difference plots. RESULTS: Automated granulocyte counts from the Cell-Dyn were in good agreement with manual granulocyte counts (r = 0.93 and 0.80 for the 2 study groups). No correlation was found between automated and manual lymphocyte counts. Correlation coefficients for monocyte counts were 0.70 and 0.43. CONCLUSION: Automated leukocyte results from the Cell-Dyn using VET 2.3 software were not fully accurate. Total granulocyte counts may be of clinical usefulness, but results obtained for other parameters were unreliable.

Animals↗

Automated evoked potential monitoring.

We have developed a computer system for use in the operating room and intensive care unit for the automated acquisition and classification of flash evoked potentials. The project goals were to: (1) acquire evoked potentials without user intervention; (2) recognize, label, and trend important parameters; and (3) alarm if parameters deviate too far from normal. The system consists of a Nicolet Pathfinder, programmed for periodic flash visual evoked potential acquisition and a personal computer for analysis. Analysis software utilizes the C+ +language. The system has been tested on sixteen cases, determinations of specific waveforms were validated ex post facto by two experts. Three parameters in each of three channels were correctly recognized in more than 87% of all waveforms acquired. No signals at all were obtained in only 0.8% of all samples.

Diagnosis, Computer-Assisted↗

3D CT-based cephalometric analysis: 3D cephalometric theoretical concept and software.

INTRODUCTION: We present an original three-dimensional cephalometric analysis based on a transformation of a classical two dimensional topological cephalometry. METHODS: To validate the three-dimensional cephalometric CT based concept we systematically compared the alignments of anatomic structures. We used digital lateral radiography to perform the classical two-dimensional cephalometry, and a three-dimensional CT surface model for the three-dimensional cephalometry. RESULTS: Diagnoses based on both two-dimensional and three-dimensional analyses were adequate, but the three-dimensional analysis gave more information such as the possibility of comparing the right and left side of the skull. Also the anatomic structures were not superimposed which improved the visibility of the reference landmarks. CONCLUSION: We demonstrated that three-dimensional analysis gives the same results as two-dimensional analysis using the same skull. We also present possible applications of the method.

Cephalometry↗

Construct validity for the LAPSIM laparoscopic surgical simulator.

BACKGROUND: The skills required for laparoscopic surgery are amenable to simulator-based training. Several computerized devices are now available. We hypothesized that the LAPSIM simulator can be shown to distinguish novice from experienced laparoscopic surgeons, thus establishing construct validity. METHODS: We tested residents of all levels and attending laparoscopic surgeons. The subjects were tested on eight software modules. Pass/fail (P/F), time (T), maximum level achieved (MLA), tissue damage (TD), motion, and error scores were compared using the t-test and analysis of variance. RESULTS: A total of 54 subjects were tested. The most significant difference was found when we compared the most (seven attending surgeons) and least experienced (10 interns) subjects. Grasping showed significance at P/F and MLA (p < 0.03). Clip applying was significant for P/F, MLA, motion, and errors (p < 0.02). Laparoscopic suturing was significant for P/F, MLA, T, TD, as was knot error (p < 0.05). This finding held for novice, intermediate, and expert subjects (p < 0.05) and for suturing time between attending surgeons and residents (postgraduate year [PGY] 1-4) (p < 0.05). CONCLUSIONS: LAPSIM has construct validity to distinguish between expert and novice laparoscopists. Suture simulation can be used to discriminate between individuals at different levels of residency and expert surgeons.

Clinical Competence↗

Predicting the carcinogenic potential of pharmaceuticals in rodents using molecular structural similarity and E-state indices.

MDL QSAR (formerly SciVision QSAR IS) software is one of the several software systems under evaluation by the Informatics and Computational Safety Analysis Staff (ICSAS) of the FDA Center for Drug Evaluation and Research for regulatory and scientific decision support applications. MDL QSAR software contains an integrated set of tools for similarity searching, compound clustering, and modeling molecular structure related parameters that includes 240 electrotopological E-state, connectivity, and other descriptors. These molecular descriptors can be statistically correlated with toxicological or biological endpoints. The goal of this research was to evaluate the feasibility of using MDL QSAR software to develop structure-activity relationship (SAR) models that can be used to predict the carcinogenic potential of pharmaceuticals and organic chemicals. A validation study of 108 compounds that include 86 pharmaceuticals and 22 chemicals that were not present in a control rodent carcinogenicity data set of 1275 compounds demonstrated that MDL QSAR models had excellent coverage (93%) and good sensitivity (72%) and specificity (72%) for rodent carcinogenicity. The software correctly predicted 72% of non-carcinogenic compounds and compounds with carcinogenic findings. E-state descriptors contributed to more than half of the SAR models used to predict carcinogenic activity. We believe that electrotopological E-state descriptors and QSAR IS (MDL QSAR) software are promising new in silico approaches for modeling and predicting rodent carcinogenicity and may have application for other toxicological endpoints.

Algorithms↗

Measurement of the orbitofrontal cortex: a validation study of a new method.

The orbital frontal cortex (OFC) plays a critical role in the pathophysiology of several neuropsychiatric disorders. Few morphometric neuroimaging studies have examined the OFC using different methodologies and have reported discrepant values. Substantial variability in gyri and sulci across individuals as well as unclear landmarks underline the difficulties in obtaining accurate and reliable measurements. We propose a new geometrical method for measuring the OFC taking into account individual brain variability. The OFC was defined by using the intercommissural line and the inferior edge of the frontal lobe as the main landmarks. The medial and lateral subdivisions of OFC were also separately measured using the olfactory sulcus as the boundary to distinguish between them. After resampling and refitting, 10 scans were independently traced by two trained researchers using BRAINS software. Talairach coordinates were identified on each scan from the OFC and surrounding adjacent brain regions to assess the validity of this method. Brain regions were assigned using Talairach Daemon system. OFC volumes were comparable with those previously reported. Sensitivity and specificity for OFC gray matter were 87.6 and 84.8%, respectively. Intraclass coefficients (ICCs) for gray, white, and total OFC were 0.995, 0.994, and 0.997, respectively. ICCs for OFC medial and lateral subdivisions ranged between 0.996 and 0.998. This method appears to be a valid method for measuring the OFC with excellent reliability. This uncomplicated approach is easy to apply and has the potential to be a valuable alternative to the previously published methods.

Adult↗

i-Tracker: for quantitative proteomics using iTRAQ.

BACKGROUND: iTRAQ technology for protein quantitation using mass spectrometry is a recent, powerful means of determining relative protein levels in up to four samples simultaneously. Although protein identification of samples generated using iTRAQ may be carried out using any current identification software, the quantitation calculations have been restricted to the ProQuant software supplied by Applied Biosciences. i-Tracker software has been developed to extract reporter ion peak ratios from non-centroided tandem MS peak lists in a format easily linked to the results of protein identification tools such as Mascot and Sequest. Such functionality is currently not provided by ProQuant, which is restricted to matching quantitative information to the peptide identifications from Applied Biosciences' Interrogator software. RESULTS: i-Tracker is shown to generate results that are consistent with those produced by ProQuant, thus validating both systems. CONCLUSION: i-Tracker allows quantitative information gained using the iTRAQ protocol to be linked with peptide identifications from popular tandem MS identification tools and hence is both a timely and useful tool for the proteomics community.

Algorithms↗

Interrater agreement with a standard scheme for classifying medication errors.

PURPOSE: The interrater agreement for and reliability of the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) index for categorizing medication errors were determined. METHODS: A letter was sent by the U.S. Pharmacopeia to all 550 contacts in the MEDMARX system user database. Participants were asked to categorize 27 medication scenarios using the NCC MERP index and were randomly assigned to one of three tools (the index alone, a paper-based algorithm, or a computer-based algorithm) to assist in categorization. Because the NCC MERP index accounts for harm and cost, and because categories could be interpreted as substantially similar, study results were analyzed after the nine error categories were collapsed to six. The interrater agreement was measured using Cohen's kappa value. RESULTS: Of 119 positive responses, 101 completed surveys were returned for a response rate of 85%. There were no significant differences in baseline demographics among the three groups. The overall interrater agreement for the participants, regardless of group assignment, was substantial at 0.61 (95% confidence interval [CI], 0.41-0.81). There was no difference among the kappa values of the three study groups and the tools used to aid in medication error classification. When the index was condensed from nine categories to six, the interrater agreement increased with a kappa value of 0.74 (95% CI, 0.56-0.90). CONCLUSION: Overall interrater agreement for the NCC MERP index for categorizing medication errors was substantial. The tool provided to assist with categorization did not influence overall categorization. Further refining of the scale could improve the usefulness and validity of medication error categorization.

Adverse Drug Reaction Reporting Systems↗

Application of GESPECOR software for the calculation of coincidence summing effects in special cases.

In this work, coincidence summing correction factors have been measured for 133Ba, 152Eu and 88Y point sources with a 50% relative efficiency p-type detector and a 25% relative efficiency n-type detector in two close-to-detector measurement geometries. The experimental data for 133Ba and 152Eu and the results obtained with the GESPECOR software reveal a complex structure of the conventional dead layer of the p-type detector. The high value of the coincidence summing correction factor for the 511 keV peak of 88Y, in agreement with the values computed by GESPECOR, in this case cautions against the application of the semiempirical method for evaluating coincidence summing effects.

Algorithms↗

Analysis of gene expression profiles: an application of memetic algorithms to the minimum sum-of-squares clustering problem.

Microarrays have become a key technology in experimental molecular biology since they allow monitoring of gene expression for more than 10,000 genes in parallel producing huge amounts of data. In the exploration of transcriptional regulatory networks, an important task is to cluster gene expression data to identify groups of genes with similar patterns and hence similar function. In this paper, memetic algorithms (MAs)-evolutionary algorithms incorporating local search-are proposed for minimum sum-of-squares clustering (MSSC). In a fitness landscape analysis, it is shown that the MSSC problem has correlation structure exploitable by MAs. The proposed MAs are shown to be superior to multi-start k-means as well as five other clustering algorithms from the bioinformatics literature including hierarchical algorithms and self-organizing maps. Although the fitness values of the different clustering solutions lie close together, it is shown that the solutions differ significantly from each other in terms of cluster memberships which is extremely important for the biological interpretation of the clustering results.

Algorithms↗

Simultaneous spectrophotometric determination of cyproterone acetate and estradiol valerate in pharmaceutical preparations by ratio spectra derivative and chemometric methods.

Ratio spectra derivative spectrophotometry and two chemometric methods (classical least squares, CLS and inverse least squares, ILS, were proposed for the simultaneous quantitative analysis of a binary mixture consists of cyproterone acetate (CA) and estradiol valerate (EV) in the commercial pharmaceutical preparations. In the ratio spectra derivative method, linear regression equations for both drugs were obtained by measuring the analytical signals at the wavelenghts corresponding to either maximums and minimums in the first derivative spectra of the ratio spectra. In the chemometric techniques, the concentration matrix was prepared by using the synthetic mixtures containing these drugs. The absorbance matrix corresponding to the concentration matrix was obtained by measuring the absorbances at 14 wavelengths in the range 220-290 nm for the zero-order spectra. Two chemometric calibrations were constructed by using the absorbance matrix and concentration matrix for the prediction of the unknown concentrations of CA and EV in their mixture. The numerical values were calculated by using 'MAPLE V' software. The accuracy and the precision of the methods have been determined and they have been validated by analyzing synthetic mixtures containing these two drugs. The proposed methods were successfully applied to a pharmaceutical formulation, sugar-coated tablet, and the results were compared with each other.

Algorithms↗

Efficient screening of covariates in population models using Wald's approximation to the likelihood ratio test.

We propose an efficient algorithm for screening covariates in population model building using Wald's approximation to the likelihood ratio test (LRT) statistic in conjunction with Schwarz's Bayesian criterion. The algorithm can be applied to a full model fit of k covariate parameters to calculate the approximate LRT for all 2k - 1 possible restricted models. The algorithm's efficiency also permits internal validation of the model selection process via bootstrap methods. We illustrate the use of this algorithm for both model selection and validation with data from a Daypro pediatric study. The algorithm is easily implemented using standard statistical software such as SAS/IML and S-Plus. A SAS/IML macro to perform the algorithm is provided.

Adult↗

Quantitation of transverse maxillary dimensions using computed tomography: a methodological and reproducibility study.

The present investigation was a methodological study of a new method of quantification of a series of factors in the transverse dimension of the maxilla including the nose, maxillary bones and dental arches, based on computer tomographic (CT) scanning. The aim was to investigate a series of parameters thought to be relevant in the differential diagnosis of discrepancies in the morphology of this area and probably affected by orthodontic appliances. Based on a standardized CT scanning registration of 10 subjects, a series of points on the scans were identified and then measured in a special cephalometric computer system (linear and angular values). The quantitation was repeated by each observer and inter- and intra-observer differences were calculated. The results demonstrated that virtually all the parameters showed a high degree of reproducibility at both levels and confirmed the statistical suitability of the method described. The method will be used in a series of ongoing studies regarding the morphology and treatment of discrepancies of the midface and therefore supplement the relatively sparse information based on quantitative reports concerning this important anatomical area.

Adult↗

The Organelle Genome Database Project (GOBASE).

The taxonomically broad organelle genome database (GOBASE) organizes and integrates diverse data related to organelles (mitochondria and chloroplasts). The current version of GOBASE focuses on the mitochondrial subset of data and contains molecular sequences, RNA secondary structures and genetic maps, as well as taxonomic information for all eukaryotic species represented. The database has been designed so that complex biological queries, especially ones posed in a comparative genomics context, are supported. GOBASE has been implemented as a relational database with a web-based user interface (http://megasun.bch.umontreal.ca/gobase/gobas e.html ). Custom software tools have been written in house to assist in the population of the database, data validation, nomenclature standardization and front-end design. The database is fully operational and publicly accessible via the World Wide Web, allowing interactive browsing, sophisticated searching and easy downloading of data.

Amino Acid Sequence↗

Shotgun haplotyping: a novel method for surveying allelic sequence variation.

Haplotypic sequences contain significantly more information than genotypes of genetic markers and are critical for studying disease association and genome evolution. Current methods for obtaining haplotypic sequences require the physical separation of alleles before sequencing, are time consuming and are not scaleable for large surveys of genetic variation. We have developed a novel method for acquiring haplotypic sequences from long PCR products using simple, high-throughput techniques. This method applies modified shotgun sequencing protocols to sequence both alleles concurrently, with read-pair information allowing the two alleles to be separated during sequence assembly. Although the haplotypic sequences can be assembled manually from the resultant data using pre-existing sequence assembly software, we have devised a novel heuristic algorithm to automate assembly and remove human error. We validated the approach on two long PCR products amplified from the human genome and confirmed the accuracy of our sequences against full-length clones of the same alleles. This method presents a simple high-throughput means to obtain full haplotypic sequences potentially up to 20 kb in length and is suitable for surveying genetic variation even in poorly-characterized genomes as it requires no prior information on sequence variation.

Algorithms↗

In vitro 2-D networks of neurons characterized by processing the signals recorded with a planar microtransducer array.

The purpose of this paper is to extensively analyze and utilize the key features that characterize the recently available electrophysiological technique of growing selected populations of neurons on planar substrate microelectrode arrays. This experimental configuration is first simulated by modeling the signal transduction operated by an array of microtransducers coupled to a network of Hodgkin-Huxley-like neurons, connected to each other with given levels of synaptic strength. Signal processing tools are then described and validated by identifying the various degrees of connectivity previously introduced into the simulated network. Finally, these software tools are utilized to characterize the activity and identify the synaptic connectivity of networks of cultured neurons extracted from dorsal root ganglia (DRG) of chick embryos and exposed to synapse inhibiting/reinforcing ions. As a result, correlations between various regimens of electrophysiological activity and synaptic strength are obtained.

Algorithms↗

Design of vector quantizer for image compression using self-organizing feature map and surface fitting.

We propose a new scheme of designing a vector quantizer for image compression. First, a set of codevectors is generated using the self-organizing feature map algorithm. Then, the set of blocks associated with each code vector is modeled by a cubic surface for better perceptual fidelity of the reconstructed images. Mean-removed vectors from a set of training images is used for the construction of a generic codebook. Further, Huffman coding of the indices generated by the encoder and the difference-coded mean values of the blocks are used to achieve better compression ratio. We proposed two indices for quantitative assessment of the psychovisual quality (blocking effect) of the reconstructed image. Our experiments on several training and test images demonstrate that the proposed scheme can produce reconstructed images of good quality while achieving compression at low bit rates. Index Terms-Cubic surface fitting, generic codebook, image compression, self-organizing feature map, vector quantization.

Algorithms↗

Assessing body composition and changes in body composition. Another look at dual-energy X-ray absorptiometry.

Dual-energy X-ray absorptiometry (DXA) is selected with increasing frequency as a method for both assessing body composition and measuring the changes in body composition. Issues have been raised about hydration, software version, hardware (fan beam vs. pencil beam), and the subject population in relation to the validity of DXA-derived estimates of body composition. This paper reviews validation studies of DXA to assess the impact of recent developments in its technology. Studies by Prior et al., Kohrt et al., Salamone et al., Going et al., and Pietrobelli et al. demonstrate the effectiveness of DXA estimates of changes in body composition. By contrast, Clasey et al., Nelson et al., and Friedl et al. found limitations in DXA estimates of body composition and its changes. These contradictory conclusions were explored for threats to internal validity in each research study. From this analysis, two validation guidelines are recommended for use when evaluating estimates of body composition. When multicomponent models are used, it is essential that estimates of body water as a fraction of fat-free mass fall in the expected range (71 to 75%) and have a relatively small standard deviation (2 to 3%). For measuring changes in body composition, DXA estimates of total body mass must accurately reflect both baseline and posttreatment scale body weight estimates. Failure to meet these guidelines threatens the internal validity of the study and raises the likelihood of methodological discrepancies. Applying these criteria to DXA studies of body composition under review accounts for much of the contradictory conclusions among investigations.

Absorptiometry, Photon↗