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At least 1,621 records · Page 90Linked to original sources
PubMed2003

The KickStrip: a novel testing device for periodic limb movement disorder.

STUDY OBJECTIVES: In light of the ongoing debate over the clinical significance of periodic limb movement disorder (PLMD) and its monitoring in overnight sleep studies, we introduce a novel, portable, low-cost device for PLMD testing. The KickStrip is a disposable device, which includes a movement sensor, a central processing unit with real-time software, and a display. In the present study, the KickStrip final score (Kscore) is validated against the traditional periodic limb movement index (PLMI) based on overnight recordings in the sleep laboratory. DEISGN: Patients underwent full polysomnographic recordings concomitantly with the use of the KickStrip for a single night. SETTING: Sleep Disorders Unit at Loewenstein Rehabilitation Hospital and Sleep Medicine Center at Rambam Medical Center, Israel. PATIENTS: Eighty-two patients referred for overnight sleep recordings due to sleep disturbance of any kind. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The Kscores were collected and the PLMI computed for each leg separately. Pearson correlations between Kscores and PLMI ranged between r = 0.83 to r = 0.88 (p < 0.001). Sensitivity and specificity values of the Kscores for increasing PLMD thresholds showed sensitivity ranging from 50% to 100% and specificity ranging from 83% to 100%. Receiver operating characteristic curves showed area-under-the-curve values ranging from 82% to 92%. Bland-Altman plot showed high agreement between the methods. CONCLUSIONS: Comparisons between the Kscores and the traditional PLMI show increased accuracy with severity level and excellent agreement. The KickStrip is a valuable tool for PLMD testing for both clinical and research purposes.

Adolescent↗
PubMed2002

Periodic solutions for systems of coupled nonlinear Schrödinger equations with five and six components.

Systems of coupled nonlinear Schrödinger (CNLS) equations arise in several branches of physics, e.g., optics and plasma physics. Systems with two or three components have been studied intensively. Recently periodic solutions for CNLS systems with four components are derived. The present work extends the search of periodic solutions for CNLS systems to those with five and six components. The Hirota bilinear method, theta and elliptic functions are employed in the process. The long wave limit is studied, and known results of solitary waves are recovered. The validity of these periodic solutions is verified independently by direct differentiation with computer algebra software.

Journal Article↗
PubMed2004

Delineation and analysis of the conceptual data model implied by the "IUPAC Recommendations for Biochemical Nomenclature".

Computational analysis of the bonding, geometric, and topological relationships within proteins typically takes on the order of hours, mainly devoted to the writing of scripts and code to correctly parse the data. The Structured Query Language (SQL) built into modern database management systems eliminates the need for data parsing, effectively reducing the analysis time to seconds. To this end, we have formulated a conceptual data model (CDM) for proteins based on the IUPAC recommendations for biochemical nomenclature. This conceptual data model makes explicit the inherent bonding relationships between the atoms of a protein, as well as the geometric (bond angle and torsion angle) and topological (chirality) relationships between the bonds. The validity of the CDM has been tested with a reduced implementation using commercial database software. The ease in both populating the database with data from the Protein Data Bank and formulating/executing queries supports the correctness of the model. The ability to conduct truly interactive analyses of protein structure is essential to fully capitalize on the explosion in postgenomic protein structure data.

Biochemical Phenomena↗
PubMed2006

Population pharmacokinetic parameters of vancomycin in critically ill patients.

BACKGROUND: Intensive care unit patients are a highly heterogeneous population. Accurate dosing for this population requires characterization of the appropriate pharmacokinetic parameters. OBJECTIVE: To estimate population pharmacokinetic parameters of vancomycin (VAN) in adult critically ill patients and to establish the predictive performance of the resulting model. PATIENTS AND METHOD: Fifty critically ill patients with suspected or documented infection with VAN-sensitive micro-organisms were included. Thirty patients and 234 serum concentration-time sets obtained during clinical routine monitoring were used to estimate the pharmacokinetic parameters (group A). An open bicompartimental model with intermittent intravenous administration was used to adjust the data. Data were evaluated using a nonlinear mixed effects model (nonmem software). Forty plasma concentration-time data sets from 20 patients were used for validation using the Bayesian method (group B). RESULTS: There was a linear relationship between creatinine clearance (Cl(cr)) and VAN clearance (Cl(VAN)). The inclusion of the non-renal clearance (Cl(nr)) (intercept of Cl(VAN) vs. Cl(cr) relationship) improved the model significantly (Cl(nr) 17 mL/min). The volume of distribution seems to be larger than previously reported: volume of the central compartment (V(c)) was 0.41 L/kg and volume of the peripheral compartment was (V(p)), 1.32 L/kg. The mean error (bias) and mean absolute error (precision) for predicting subsequent peak concentrations were -2.16 and 9.28 mg/L and for trough concentrations, -0.22 and 3.87 mg/L respectively. CONCLUSION: The use of population-specific pharmacokinetic parameters and Bayesian forecasting improves dosage-regimen design.

Adolescent↗
PubMed2006

Integrating software into PRA: a software-related failure mode taxonomy.

Probabilistic risk assessment is a methodology to assess the probability of failure or success of a mission. Results provided by the risk assessment methodology are used to make decisions concerning choice of upgrades, scheduling of maintenance, decision to launch, etc. However, current PRA neglects the contribution of software to the risk of failure of the mission. Our research has developed a methodology to account for the impact of software to system failure. This article focuses on an element of the approach: a comprehensive taxonomy of software-related failure modes. Application of the taxonomy is discussed in this article. A validation of the taxonomy and conclusions drawn from this validation effort are described. Future research is also summarized.

Journal Article↗
PubMed2003

Calculations for plane-parallel ion chambers in 60Co beams using the EGSnrc Monte Carlo code.

The EGSnrc Monte Carlo simulation system is used to obtain, for 10 plane-parallel ionization chambers in 60Co beams, the correction factors Kcomp and Pwall that account for the nonequivalence of the chamber wall material to the buildup cap and the phantom material, respectively. A more robust calculation method has been used compared to that used in previous works. A minor conceptual error related to the axial nonuniformity correction factor, Kan, has been identified and shown to have an effect of about 0.2%. The assumption that Pwall in-phantom is numerically equal to Kcomp calculated for a water buildup cap is shown to be accurate to better than 0.06%, thereby justifying the use of Kcomp calculations which are much more efficient. The effect on the calculated dose to the air in the cavity of the particle production threshold and transport energies used in the simulations is studied. Uncertainties in the calculated correction factors due to uncertainties in the photon and electron cross-section data are studied. They are 0.14% and 0.24%, respectively (1 standard deviation), for Kcomp factors. The uncertainties on Kwall factors are 0.03% from photon cross-section uncertainties and negligible from electron cross-section uncertainties. A comparison with previous EGS4/PRESTA calculations shows that present results are systematically higher by an average of 0.8%, ranging from 0.4% up to 1.4%. The present results are in better agreement with reported experimental values.

Algorithms↗
PubMed2004

An investigation of accelerator head scatter and output factor in air.

Our purpose in this study was to investigate whether the Monte Carlo simulation can accurately predict output factors in air. Secondary goals were to study the head scatter components and investigate the collimator exchange effect. The Monte Carlo code, BEAMnrc, was used in the study. Photon beams of 6 and 18 MV were from a Varian Clinac 2100EX accelerator and the measurements were performed using an ionization chamber in a mini-phantom. The Monte Carlo calculated in air output factors was within 1% of measured values. The simulation provided information of the origin and the magnitude of the collimator exchange effect. It was shown that the collimator backscatter to the beam monitor chamber played a significant role in the beam output factors. However the magnitude of the scattered dose contributions from the collimator at the isocenter is negligible. The maximum scattered dose contribution from the collimators was about 0.15% and 0.4% of the total dose at the isocenter for a 6 and 18 MV beam, respectively. The scattered dose contributions from the flattening filter at the isocenter were about 0.9-3% and 0.2-6% of the total dose for field sizes of 4x4 cm2-40x40 cm2 for the 6 and 18 MV beam, respectively. The study suggests that measurements of head scatter factors be done at large depth well beyond the depth of electron contamination. The insight information may have some implications for developing generalized empirical models to calculate the head scatter.

Air↗
PubMed2003

Automated identification of single nucleotide polymorphisms from sequencing data.

The single nucleotide polymorphism (SNP) is the difference of the DNA sequence between individuals and provides abundant information about genetic variation. Large scale discovery of high frequency SNPs is being undertaken using various methods. However, the publicly available SNP data sometimes need to be verified. If only a particular gene locus is concerned, locus-specific polymerase chain reaction amplification may be useful. Problem of this method is that the secondary peak has to be measured. We have analyzed trace data from conventional sequencing equipment and found an applicable rule to discern SNPs from noise. The rule is applied to multiply aligned sequences with a trace and the peak height of the traces are compared between samples. We have developed software that integrates this function to automatically identify SNPs. The software works accurately for high quality sequences and also can detect SNPs in low quality sequences. Further, it can determine allele frequency, display this information as a bar graph and assign corresponding nucleotide combinations. It is also designed for a person to verify and edit sequences easily on the screen. It is very useful for identifying de novo SNPs in a DNA fragment of interest.

Algorithms↗
PubMed2005

Cardiac three-dimensional magnetic resonance imaging and fluoroscopy merging: a new approach for electroanatomic mapping to assist catheter ablation.

BACKGROUND: Modern nonfluoroscopic mapping systems construct 3D electroanatomic maps by tracking intracardiac catheters. They require specialized catheters and/or dedicated hardware. We developed a new method for electroanatomic mapping by merging detailed 3D models of the endocardial cavities with fluoroscopic images without the need for specialized hardware. This developmental work focused on the right atrium because of the difficulties in visualizing its anatomic landmarks in 3D with current approaches. METHODS AND RESULTS: Cardiac MRI images were acquired in 39 patients referred for radiofrequency catheter ablation using balanced steady state free-precession sequences. We optimized acquisition and developed software for construction of detailed 3D models, after contouring of endocardial cavities with cross-checking of different imaging planes. 3D models were then merged with biplane fluoroscopic images by methods for image calibration and registration implemented in a custom software application. The feasibility and accuracy of this merging process were determined in heart-cast experiments and electroanatomic mapping in patients. Right atrial dimensions and relevant anatomic landmarks could be identified and measured in all 3D models. Cephalocaudal, posteroanterior, and lateroseptal diameters were, respectively, 65+/-11, 54+/-11, and 57+/-9 mm; posterior isthmus length was 26+/-6 mm; Eustachian valve height was 5+/-5 mm; and coronary sinus ostium height and width were 16+/-3 and 12+/-3 mm, respectively (n=39). The average alignment error was 0.2+/-0.3 mm in heart casts (n=40) and 1.9 to 2.5 mm in patient experiments (n=9), ie, acceptable for clinical use. In 11 patients, reliable catheter positioning and projection of activation times resulted in 3D electroanatomic maps with an unprecedented level of anatomic detail, which assisted ablation. CONCLUSIONS: This new approach allows activation visualization in a highly detailed 3D anatomic environment without the need for a specialized nonfluoroscopic mapping system.

Arrhythmias, Cardiac↗
PubMed2005

Automated methods of predicting the function of biological sequences using GO and BLAST.

BACKGROUND: With the exponential increase in genomic sequence data there is a need to develop automated approaches to deducing the biological functions of novel sequences with high accuracy. Our aim is to demonstrate how accuracy benchmarking can be used in a decision-making process evaluating competing designs of biological function predictors. We utilise the Gene Ontology, GO, a directed acyclic graph of functional terms, to annotate sequences with functional information describing their biological context. Initially we examine the effect on accuracy scores of increasing the allowed distance between predicted and a test set of curator assigned terms. Next we evaluate several annotator methods using accuracy benchmarking. Given an unannotated sequence we use the Basic Local Alignment Search Tool, BLAST, to find similar sequences that have already been assigned GO terms by curators. A number of methods were developed that utilise terms associated with the best five matching sequences. These methods were compared against a benchmark method of simply using terms associated with the best BLAST-matched sequence (best BLAST approach). RESULTS: The precision and recall of estimates increases rapidly as the amount of distance permitted between a predicted term and a correct term assignment increases. Accuracy benchmarking allows a comparison of annotation methods. A covering graph approach performs poorly, except where the term assignment rate is high. A term distance concordance approach has a similar accuracy to the best BLAST approach, demonstrating lower precision but higher recall. However, a discriminant function method has higher precision and recall than the best BLAST approach and other methods shown here. CONCLUSION: Allowing term predictions to be counted correct if closely related to a correct term decreases the reliability of the accuracy score. As such we recommend using accuracy measures that require exact matching of predicted terms with curator assigned terms. Furthermore, we conclude that competing designs of BLAST-based GO term annotators can be effectively compared using an accuracy benchmarking approach. The most accurate annotation method was developed using data mining techniques. As such we recommend that designers of term annotators utilise accuracy benchmarking and data mining to ensure newly developed annotators are of high quality.

Benchmarking↗
PubMed2002

Simulating the swelling and deformation behaviour in soft tissues using a convective thermal analogy.

BACKGROUND: It is generally accepted that cartilage adaptation and degeneration are mechanically mediated. Investigating the swelling behaviour of cartilage is important because the stress and strain state of cartilage is associated with the swelling and deformation behaviour. It is well accepted that the swelling of soft tissues is associated with mechanical, chemical, and electrical events. METHOD: The purpose of the present study was to implement the triphasic theory into a commercial finite element tool (ABAQUS) to solve practical problems in cartilage mechanics. Because of the mathematical identity between thermal and mass diffusion processes, the triphasic model was transferred into a convective thermal diffusion process in the commercial finite element software. The problem was solved using an iterative procedure. RESULTS: The proposed approach was validated using the one-dimensional numerical solutions and the experimental results of confined compression of articular cartilage described in the literature. The time-history of the force response of a cartilage specimen in confined compression, which was subjected to swelling caused by a sudden change of saline concentration, was predicted using the proposed approach and compared with the published experimental data. CONCLUSION: The advantage of the proposed thermal analogy technique over previous studies is that it accounts for the convective diffusion of ion concentrations and the Donnan osmotic pressure in the interstitial fluid.

Adaptation, Physiological↗
PubMed2006

Using several pair-wise informant sequences for de novo prediction of alternatively spliced transcripts.

BACKGROUND: As part of the ENCODE Genome Annotation Assessment Project (EGASP), we developed the MARS extension to the Twinscan algorithm. MARS is designed to find human alternatively spliced transcripts that are conserved in only one or a limited number of extant species. MARS is able to use an arbitrary number of informant sequences and predicts a number of alternative transcripts at each gene locus. RESULTS: MARS uses the mouse, rat, dog, opossum, chicken, and frog genome sequences as pairwise informant sources for Twinscan and combines the resulting transcript predictions into genes based on coding (CDS) region overlap. Based on the EGASP assessment, MARS is one of the more accurate dual-genome prediction programs. Compared to the GENCODE annotation, we find that predictive sensitivity increases, while specificity decreases, as more informant species are used. MARS correctly predicts alternatively spliced transcripts for 11 of the 236 multi-exon GENCODE genes that are alternatively spliced in the coding region of their transcripts. For these genes a total of 24 correct transcripts are predicted. CONCLUSION: The MARS algorithm is able to predict alternatively spliced transcripts without the use of expressed sequence information, although the number of loci in which multiple predicted transcripts match multiple alternatively spliced transcripts in the GENCODE annotation is relatively small.

Algorithms↗
PubMedDate not supplied

Challenges of high throughput screening against cell surface receptors.

Excessive or inappropriate activation of cell surface receptors can mediate the development of disease. Receptors, therefore, are a focus for drug discovery activities. Empirical screening is important in the search for novel compounds acting as receptors. Technical developments and the application of molecular biology have facilitated access to receptors of interest and have provided efficient screening methods capable of very high throughput. Reliability in high throughput screening requires the use of appropriate methodology, good screen design and effective validation and quality control processes. Validation should aim to establish that the basic experimental design is sound. In developing software to handle high throughput screening data, a fundamental requirement is to provide performance monitoring and error trapping facilities. Additional requirements are automatic data capture from instruments, on-line data reduction and analysis and transfer of results to central databases. As data volumes increase through effective high throughput screening, conventional interrogation methods become less appropriate and are being augmented by newer computing techniques referred to as knowledge mapping or database mining. Targeting cell surface receptors has been very successful as an approach to drug discovery. If the challenges of high throughput empirical screening are addressed effectively, cell surface receptors will provide new opportunities for improved therapy in the coming years.

Animals↗
PubMed1997

The Stroke Prevention Policy Model: linking evidence and clinical decisions.

Simulation models that support decision and cost-effectiveness analysis can further the goals of evidence-based medicine by facilitating the synthesis of information from several sources into a single comprehensive structure. The Stroke Prevention Policy Model (SPPM) performs this function for the clinical and policy questions that surround stroke prevention. This paper first describes the basic structure and functions of the SPPM, concentrating on the role of large databases (broadly defined as any database that contains many patients, regardless of study design) in providing the SPPM inputs. Next, recognizing that the use of modeling continues to be a source of some controversy in the medical community, it discusses the philosophical underpinnings of the SPPM. Finally, it discusses conclusions in the context of both stroke prevention and other complex medical decisions. We conclude that despite the difficulties in developing comprehensive models (for example, the length and complexity of model development and validation processes, the proprietary nature of data sources, and the necessity for developing new software), the benefits of such models exceed the costs of continuing to rely on more conventional methods. Although they should not replace the clinician in decision making, comprehensive models based on the best available evidence from large databases can support decision making in medicine.

Cerebrovascular Disorders↗
PubMed2003

[Tractography of the visual pathways: routine examination in magnetic resonance imaging].

Water diffusion analysis in magnetic resonance imaging (MRI) provides an elective visualization of fiber tract orientations in cerebral white matter, especially for optic tracts. We explored 25 patients from 18 to 45 years of age, with normal MRI in 20 subjects, and radiological anomalies in five. On a 1.5 Tesla MRI apparatus, diffusion tensor acquisitions were performed in 5 minutes 58 seconds with an EPI Single Shot sequence covering the entire brain. Image displacements were precluded by patient information and adequate fixation, then digitally corrected on workstations. Volume merging and fiber tract extraction were achieved using dedicated software (Volume-One and dTV). A directional depiction was obtained for all areas in the white matter, in particular for white matter junctions. Coming from the lateral geniculate body, the optic tracts were directed posteriorly toward the occipital cortex, with numerous connections to extrastriate associative areas, and through the corpus callosum and the fornix. Diffusion tractography requires optimization of volume displacements, before and secondary to MRI acquisitions. Our diffusion tensor acquisition, with image optimization in a short-duration sequence can be routinely applied to all patients, for a specific analysis of functional connections between cortical areas of cerebral white matter.

Adolescent↗
PubMed2003

Text mining of DNA sequence homology searches.

Primary tasks in analysis and annotation of expressed sequence tag (EST) datasets are to identify similarity among sequences by unsupervised clustering and assign putative function based on BLAST homology searches. We investigated the usefulness of text mining as a simple approach for further higher-level clustering of EST datasets using IBM Intelligent Miner for Text v2.3 tools. Agglomerative and k-means clustering tools were used to cluster BLASTx homology search documents from two onion EST datasets and optimised by pre-processing and pruning. Subjective evaluation confirmed that these tools provided biologically useful and complementary views of the two libraries, provided new insights into their composition and revealed clusters previously identified by human experts. We compared BLASTx textual clusters for two gene families with their DNA sequence-based clusters and confirmed that these shared similar morphology.

Abstracting and Indexing↗
PubMed2003

Identification of differentially expressed genes in keratoconus epithelium analyzed on microarrays.

PURPOSE: The present study was conducted to investigate differential gene expression in individual samples derived from fresh-frozen human keratoconus and normal corneal epithelium, using gene microarrays. METHODS: Total RNA was extracted (11 keratoconus and 8 normal samples), labeled, and hybridized to microarrays (GeneChip; Affymetrix, Inc., Santa Clara, CA). GeneChip data were validated by verifying the expression profiles of 10 genes by real-time PCR and by recalculation using dChip software (Wong Laboratory, Department of Biostatistics, Harvard School of Public Health, Boston, MA). Furthermore, 3 of the 10 encoded proteins were stained by immunohistochemistry. RESULTS: In comparison with normal cornea, the expression of 471 of the 5600 genes on the microarrays was changed in the keratoconus samples. This number was reduced to 47 with increased expression and 9 with decreased expression when more stringent selection parameters were applied. These genes are believed to be involved in keratoconus. Two of the candidate genes, lysyl oxidase and tissue inhibitor of metalloproteinase 3, are known to be involved in other eye diseases. Expression profiles were reproduced with the software dChip (Wong Laboratory) and real-time PCR. Increases in keratin 6 and 13 were also detected at the protein level. CONCLUSIONS: Keratoconus epithelium appears to be characterized by massive changes of the cytoskeleton, reduced extracellular matrix remodeling, altered transmembrane signaling, and modified cell-to-cell and cell-to-matrix interactions. Validation of gene expression with dChip analysis and real-time PCR indicates GeneChip to be a valid technique for investigation of epithelium from single dissected corneal samples. Association between alterations at RNA and protein levels was observed for some of the tested candidates.

Adult↗
PubMed1995

The effects of analytic software and scan analysis technique on the comparison of dual X-ray absorptiometry with dual photon absorptiometry of the hip in the elderly.

As part of a longitudinal comparison of bone mineral density (BMD) results originally obtained using a Lunar dual photon absorptiometry (DPA) scanner and later, using a Lunar dual X-ray absorptiometry (DXA) scanner, we compared femur results between DPA and DXA according to DXA analytic software (versions 1.3y and 1.4), and according to the method of placement of the femoral neck box (software algorithm or operator placement according to the appearance of the pair of images) in 58 elderly men and women. The mean BMD at each of three femoral sites was higher using DXA version 1.3y than DPA, but the use of software version 1.4 brought the BMD value closer to that of DPA at all sites. Of 58 scans, 12 (21%) were changed by the operator, resulting in an overall reduction in mean percent BMD difference between scan pairs of 79% (from 1.24% to 0.29%). Although the differences between the DPA/DXA software-driven analysis and the DPA/DXA operator-driven analysis appeared small (high r2 values and intra-class correlation coefficients), the increase in sample size that would be required for the same power to detect 2-year changes in BMD if the software-driven analysis was used instead of taking the time to perform the operator-driven analysis was 18%. The findings of this study highlight the need to account for upgrades in analytic software. Furthermore, we present a rational approach for the analysis of serial scans that has face validity and that results in smaller differences between pairs of scans performed on the same individual. The decision to adapt these methods must be based on the relative costs of reducing unwanted scan variability.

Absorptiometry, Photon↗