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At least 829 records · Page 46Linked to original sources

Real-time respiration monitoring using the radiotherapy treatment beam and four-dimensional computed tomography (4DCT)--a conceptual study.

Real-time knowledge of intra-fraction motion, such as respiration, is essential for four-dimensional (4D) radiotherapy. Surrogate-based and internal-fiducial-based methods may suffer from one or many drawbacks such as false correlation, being invasive, delivering extra patient radiation, and requiring complicated hardware and software development and implementation. In this paper we develop a simple non-surrogate, non-invasive method to monitor respiratory motion during radiotherapy treatments in real time. This method directly utilizes the treatment beam and thus imposes no additional radiation to the patient. The method requires a pre-treatment 4DCT and a real-time detector system. The method combines off-line processes with on-line processes. The off-line processes include 4DCT imaging and pre-calculating detector signals at each phase of the 4DCT based on the planned fluence map and the detector response function. The on-line processes include measuring detector signal from the treatment beam, and correlating the measured detector signal with the pre-calculated signals. The respiration phase is determined as the position of peak correlation. We tested our method with extensive simulations based on a TomoTherapy machine and a 4DCT of a lung cancer patient. Three types of simulations were implemented to mimic the clinical situations. Each type of simulation used three different TomoTherapy delivery sinograms, each with 800 to 1000 projections, as input fluences. Three arbitrary breathing patterns were simulated and two dose levels, 2 Gy/fraction and 2 cGy/fraction, were used for simulations to study the robustness of this method against detector quantum noise. The algorithm was used to determine the breathing phases and this result was compared with the simulated breathing patterns. For the 2 Gy/fraction simulations, the respiration phases were accurately determined within one phase error in real time for most projections of the treatment, except for a few projections at the start and end of the treatment in which beam intensities were extremely low. At 2 cGy/fraction dose level, the method can still determine the respiration phase very well with less than 10% of projections having more than two phases (approximately 1 s) error. This technique can also be applied in other delivery systems such as orthogonal x-ray systems, although in those cases it would entail the delivery of additional non-treatment radiation.

Algorithms↗

Field-by-field evaluation of intraoperative transoesophageal echocardiography interpretative skills.

A quality assurance system is essential for the credibility and structured growth of anaesthesiology-based transoesophageal echocardiography (TEE) programmes. We have developed software (Q/A Kappa), involving a 400-line source code, capable of directly reporting kappa correlation coefficient values, using external reviewer interpretations as the 'gold standard', and thereby allowing systematic assessment of the validity of intraoperative echocardiographic interpretation. This paper presents assessment of the validity of 240 intraoperative anaesthesiologists' echocardiographic interpretations, and, in addition, the results of field testing of this prototypical software. Data, derived from consecutive cardiac surgery patients, consisted of standardized two-dimensional transoesophageal echocardiographic, colour flow and Doppler imaging sequences. Intraoperative and off-line 'gold standard' TEE interpretations were compared for 19 fields or variables using the Q/A Kappa program. The kappa correlation coefficients were highly variable and dependent on the examination field, ranging from 0.08 for apical regional wall motion scores to 1.00 for tricuspid regurgitation grade, left atrial measurement, aortic valve anatomy and left ventricular long axis and short axis global function. The correlation coefficients were also operator dependent. These data (480 interpretations) were also manually integrated into the equation required for calculation of values of the variable kappa correlation coefficient. The relationship between Q/A Kappa-derived values and manually calculated values was highly significant (p < 0.001; r = 1.0). The implications and possible explanations of the results for particular examination fields are discussed. This study also demonstrates successful seamless functioning of this software program from data entry, segmentation into tables and valid statistical analysis. These findings suggest that it is practical to provide sophisticated continuous quality improvement TEE data on a routine basis.

Adult↗

Automated Tecan programming for bioanalytical sample preparation with EZTecan.

This paper reports the first successful automated Tecan (Tecan US, Research Triangle Park, NC) programming for bioanalytical sample analysis with an in-house developed software, called EZTecan. Based on the sample run list in the Watson Laboratory Information Management System (InnaPhase Corp., Philadelphia, PA), EZTecan can generate a Tecan program for bioanalytical sample preparation, including sample transfer, sample dilution, extraction, and reconstitution. Many built-in functions for EZTecan ensure the flexibility, quality, and efficiency of the liquid handling. It takes about 90 min to prepare two 96-well plates from sample transfer to reconstitution. Analytical results shown good inter- and intra-assay accuracy and precision, which meet the +/-15% Good Laboratory Performance acceptance criteria. With EZTecan, bioanalysts can prepare samples without writing a single line of Tecan program.

Automation↗

Three-dimensional searching for recurrent structural motifs in data bases of protein structures.

The problem of searching a data base of coordinates of proteins for substructures similar to a probe structure or motif is an important problem in computational molecular biology. It is the three-dimensional analog of the one-dimensional case of pattern matching in strings, procedures for which are widely used in molecular biology to search data bases of gene sequences. Typical applications of substructure searching are: (i) Determining whether structural features observed in one protein structure are unique or recurrent, and (ii) in predictions of protein structures, to bridge gaps in an incomplete structural model, by searching the data base for peptides that link the given starting and ending points. We describe our analysis of the problem and our experience in developing software.

Base Sequence↗

Digitization and postprocessing of plain-film radiographs for assessment of stone fragmentation after extracorporeal shockwave lithotripsy.

In 50 patients treated for urolithiasis by extracorporeal shockwave lithotripsy (ESWL++), the radiographs taken before and 1 day afterward were initially assessed by conventional radiography and subsequently after standardized digitization and postprocessing. Clinical outcome and passage of stone fragments were reevaluated 3 weeks after ESWL. Using specially developed software routines, new disintegration parameters could be obtained by detecting the number of relevant minima in light-intensity distribution along the length axis of the concrement in digitized images. Comparing the digitized images before with those after ESWL, the concremental surface and axial length in digitized images on average showed no statistically significant difference. However, the number of visually and automatically detected light-intensity minima of the concrement region in digitized images obtained 1 day after ESWL was significantly higher than prior to ESWL and correlated significantly with the number of fissure lines in the conventional images. These new features in digitized images showed a high sensitivity in predicting later passage of stone fragments. Moreover, in six of the seven patients without detectable fissure lines in the early conventional radiographs but obvious signs of concretemental disintegration 3 weeks after ESWL, there was an increase in the number of light-intensity minima in the digitized images 1 day after ESWL. Our findings indicate that this method of digitization and post-processing of radiographs may improve the assessment of ESWL effectiveness by improving standardization in the analysis of all surveyed parameters and by offering new relevant disintegration measures.

Adult↗

Compression of protein sequence databases.

We have created an algorithm for compressing a PIR database to assist individual researchers and software developers who utilize sequence database information but may not have huge storage space. The resulting compact databank contains compressed PIR information and an interface written in C which allows fast direct access to the stored information without extensive decompression of corresponding files. The databank files as well as the interface C-file can be used on both PC-compatibles and UNIX-based computers without any modifications. The interface supports all standard PIR Request Network queries (i.e. gets databank SEQ number by entry; for a defined databank SEQ number, gets specified information like: name, organism(s), keyword(s), sequence, sequence features with coordinates, etc.). In contrast with PIR Request Network, our package allows us to call PIR-contained information directly from the C programs, even on a personal computer not on a network. Our PIR-derived databank, SAGITTARIUS PIR, was implemented in the form of separate file sets. Each file set contains database information of independent types (i.e. sequences, entry indexes, organisms, etc.). On a particular computer, the available configuration of the PIR information (and storage space) can be easily changed as needed by the user without affecting retrievals of other types of stored information. Due to an original alignment-based algorithm, in the compression of protein sequences themselves, our package out-performs the well-known ZIP file compressor. For PC-compatibles, a dialogue shell is available which supports all standard PIR Request Network queries plus homology searches, alignments, etc.

Algorithms↗

A genetic algorithm for designing gene family-specific oligonucleotide sets used for hybridization: the G protein-coupled receptor protein superfamily.

MOTIVATION: Massive oligonucleotide hybridization is one of the most promising technologies of functional genome analysis. The critical point is to design appropriate sets of oligonucleotides that can be used effectively in identification by hybridization. RESULTS: Using a genetic algorithm approach, we have attempted to design sets of oligo probes capable of identifying new genes belonging to a defined gene family within a cDNA or genomic library. It is not limited by oligonucleotide length and admits the letter 'N' in the structure of the oligonucleotides selected. One of the major advantages of this approach is the low homology required to identify functional families of sequences with little homology. We have designed the oligonucleotide sets that are most selective for the cDNA clones of transmembrane G protein-coupled receptors (GPCRs), a large family of proteins that form part of a modular system of extracellular signal transduction to the intracellular second messenger pathways. The accuracy of identification has been checked on the EST library containing 713 870 cDNA sequences. A set of 15 oligos between 7 and 14 bases in length has correctly identified 70% of the GPCR cDNA collection sequences with 0.02% false positives. AVAILABILITY: The developed software is available by ftp://ftp.bionet.nsc. ru/pub/biology/ and on the Web page http://www.bionet.nsc. ru/SRCG/Oligoselector/. CONTACT: kel@.bionet.nsc.ru; sebastian. meier-ewert@gpc-ag.com

Algorithms↗

A RAPID algorithm for sequence database comparisons: application to the identification of vector contamination in the EMBL databases.

MOTIVATION: Word-matching algorithms such as BLAST are routinely used for sequence comparison. These algorithms typically use areas of matching words to seed alignments which are then used to assess the degree of sequence similarity. In this paper, we show that by formally separating the word-matching and sequence-alignment process, and using information about word frequencies to generate alignments and similarity scores, we can create a new sequence-comparison algorithm which is both fast and sensitive. The formal split between word searching and alignment allows users to select an appropriate alignment method without affecting the underlying similarity search. The algorithm has been used to develop software for identifying entries in DNA sequence databases which are contaminated with vector sequence. RESULTS: We present three algorithms, RAPID, PHAT and SPLAT, which together allow vector contaminations to be found and assessed extremely rapidly. RAPID is a word search algorithm which uses probabilities to modify the significance attached to different words; PHAT and SPLAT are alignment algorithms. An initial implementation has been shown to be approximately an order of magnitude faster than BLAST. The formal split between word searching and alignment not only offers considerable gains in performance, but also allows alignment generation to be viewed as a user interface problem, allowing the most useful output method to be selected without affecting the underlying similarity search. Receiver Operator Characteristic (ROC) analysis of an artificial test set allows the optimal score threshold for identifying vector contamination to be determined. ROC curves were also used to determine the optimum word size (nine) for finding vector contamination. An analysis of the entire expressed sequence tag (EST) subset of EMBL found a contamination rate of 0.27%. A more detailed analysis of the 50 000 ESTs in est10.dat (an EST subset of EMBL) finds an error rate of 0.86%, principally due to two large-scale projects. AVAILABILITY: A Web page for the software exists at http://bioinf.man.ac.uk/rapid, or it can be downloaded from ftp://ftp.bioinf.man.ac.uk/RAPID CONTACT: crispin@cs.man.ac.uk

Algorithms↗

Uniform integration of genome mapping data using intersection graphs.

MOTIVATION: The methods for analyzing overlap data are distinct from those for analyzing probe data, making integration of the two forms awkward. Conversion of overlap data to probe-like data elements would facilitate comparison and uniform integration of overlap data and probe data using software developed for analysis of STS data. RESULTS: We show that overlap data can be effectively converted to probe-like data elements by extracting maximal sets of mutually overlapping clones. We call these sets virtual probes, since each set determines a site in the genome corresponding to the region which is common among the clones of the set. Finding the virtual probes is equivalent to finding the maximal cliques of a graph. We modify a known maximal-clique algorithm such that it finds all virtual probes in a large dataset within minutes. We illustrate the algorithm by converting fingerprint and Alu-PCR overlap data to virtual probes. The virtual probes are then analyzed using double-linkage intersection graphs and structure graphs to show that methods designed for STS data are also applicable to overlap data represented as virtual probes. Next we show that virtual probes can produce a uniform integration of different kinds of mapping data, in particular STS probe data and fingerprint and Alu-PCR overlap data. The integrated virtual probes produce longer double-linkage contigs than STS probes alone, and in conjunction with structure graphs they facilitate the identification and elimination of anomalies. Thus, the virtual-probe technique provides: (i) a new way to examine overlap data; (ii) a basis on which to compare overlap data and probe data using the same systems and standards; and (iii) a unique and useful way to uniformly integrate overlap data with probe data.

Algorithms↗

STOCKS: STOChastic Kinetic Simulations of biochemical systems with Gillespie algorithm.

MOTIVATION: The availability of a huge amount of molecular data concerning various biochemical reactions provoked numerous attempts to study the dynamics of cellular processes by means of kinetic models and computer simulations. Biochemical processes frequently involve small numbers of molecules (e.g. a few molecules of a transcriptional regulator binding to one 'molecule' of a DNA regulatory region). Such reactions are subject to significant stochastic fluctuations. Monte Carlo methods must be employed to study the functional consequences of the fluctuations and simulate processes that cannot be modelled by continuous fluxes of matter. This provides the motivation to develop software dedicated to Monte Carlo simulations of cellular processes with the rigorously proven Gillespie algorithm. RESULTS: STOCKS, software for the stochastic kinetic simulation of biochemical processes is presented. The program uses a rigorously derived Gillespie algorithm that has been shown to be applicable to the study of prokaryotic gene expression. Features dedicated to the study of cellular processes are implemented, such as the possibility to study a process in the range of several cell generations with the application of a simple cell division model. Taking expression of Escherichia coli beta-galactosidase as an example, it is shown that the program is able to simulate systems composed of reactions varying in several orders of magnitude by means of reaction rates and the numbers of molecules involved. AVAILABILITY: The software is available at ftp://ibbrain.ibb.waw.pl/stocksand http://www.ibb.waw.pl/stocks. SUPPLEMENTARY INFORMATION: Parameters of the model of prokaryotic gene expression are available in example files of software distribution.

Algorithms↗

Sequence complexity profiles of prokaryotic genomic sequences: a fast algorithm for calculating linguistic complexity.

MOTIVATION: One of the major features of genomic DNA sequences, distinguishing them from texts in most spoken or artificial languages, is their high repetitiveness. Variation in the repetitiveness of genomic texts reflects the presence and density of different biologically important messages. Thus, deviation from an expected number of repeats in both directions indicates a possible presence of a biological signal. Linguistic complexity corresponds to repetitiveness of a genomic text, and potential regulatory sites may be discovered through construction of typical patterns of complexity distribution. RESULTS: We developed software for fast calculation of linguistic sequence complexity of DNA sequences. Our program utilizes suffix trees to compute the number of subwords present in genomic sequences, thereby allowing calculation of linguistic complexity in time linear in genome size. The measure of linguistic complexity was applied to the complete genome of Haemophilus influenzae. Maps of complexity along the entire genome were obtained using sliding windows of 40, 100, and 2000 nucleotides. This approach provided an efficient way to detect simple sequence repeats in this genome. In addition, local profiles of complexity distribution around the starts of translation were constructed for 21 complete prokaryotic genomes. We hypothesize that complexity profiles correspond to evolutionary relationships between organisms. We found principal differences in profiles of the GC-rich and other (non-GC-rich) genomes. We also found characteristic differences in profiles of AT genomes, which probably reflect individual species variations in translational regulation. AVAILABILITY: The program is available upon request from Alexander Bolshoy or at http://csweb.haifa.ac.il/library/#complex.

Algorithms↗

NCL: a C++ class library for interpreting data files in NEXUS format.

UNLABELLED: The NEXUS Class Library (NCL) is a collection of C++ classes designed to simplify interpreting data files written in the NEXUS format used by many computer programs for phylogenetic analyses. The NEXUS format allows different programs to share the same data files, even though none of the programs can interpret all of the data stored therein. Because users are not required to reformat the data file for each program, use of the NEXUS format prevents cut-and-paste errors as well as the proliferation of copies of the original data file. The purpose of making the NCL available is to encourage the use of the NEXUS format by making it relatively easy for programmers to add the ability to interpret NEXUS files in newly developed software. AVAILABILITY: The NCL is freely available under the GNU General Public License from http://hydrodictyon.eeb.uconn.edu/ncl/ SUPPLEMENTARY INFORMATION: Documentation for the NCL (general information and source code documentation) is available in HTML format at http://hydrodictyon.eeb.uconn.edu/ncl/

Databases, Bibliographic↗

Origins of introns based on the definition of exon modules and their conserved interfaces.

Central to the unraveling of the early evolution of the genome is the origin and role of introns. The evolution of the genome can be characterized by a continuous expansion of functional modules that occurs without the interruption of existing processes. The design-by-contract methodology of software development offers a modular approach to design that seeks to increase flexibility by focusing on the design of constant interfaces between functional modules. Here, it is shown that design-by-contract can offer a framework for genome evolution. The definition of an ancient exon module with identical splice sites leads to a relatively simple sequence of events that explains the role of introns, intron phase differences and the evolution of multi-exon proteins in an RNA world. An interaction of the experimentally defined six-nucleotide splicing consensus sequence together with a limited number of primitive ribozymes can account for a rapid creation of protein diversity.

Animals↗

An integrated tool for microarray data clustering and cluster validity assessment.

UNLABELLED: In this paper we present a data mining system, which allows the application of different clustering and cluster validity algorithms for DNA microarray data. This tool may improve the quality of the data analysis results, and may support the prediction of the number of relevant clusters in the microarray datasets. This systematic evaluation approach may significantly aid genome expression analyses for knowledge discovery applications. The developed software system may be effectively used for clustering and validating not only DNA microarray expression analysis applications but also other biomedical and physical data with no limitations. AVAILABILITY: The program is freely available for non-profit use on request at http://www.cs.tcd.ie/Nadia.Bolshakova/Machaon.html CONTACT: Nadia.Bolshakova@cs.tcd.ie.

Algorithms↗

Visualizing profile-profile alignment: pairwise HMM logos.

UNLABELLED: The availability of advanced profile-profile comparison tools, such as PRC or HHsearch demands sophisticated visualization tools not presently available. We introduce an approach built upon the concept of HMM logos. The method illustrates the similarities of pairs of protein family profiles in an intuitive way. Two HMM logos, one for each profile, are drawn one upon the other. The aligned states are then highlighted and connected. AVAILABILITY: A web interface offering online creation of pairwise HMM logos is available at http://www.sanger.ac.uk/Software/analysis/logomat-p. Furthermore, software developers may download a Perl package that includes methods for creation of pairwise HMM logos locally. CONTACT: bsb@sanger.ac.uk.

Computer Graphics↗

MILVA: an interactive tool for the exploration of multidimensional microarray data.

MOTIVATION: Clustering techniques such as k-means and hierarchical clustering are commonly used to analyze DNA microarray derived gene expression data. However, the interactions between processes underlying the cell activity suggest that the complexity of the microarray data structure may not be fully represented with discrete clustering methods. RESULTS: A newly developed software tool called MILVA (microarray latent visualization and analysis) is presented here to investigate microarray data without separating gene expression profiles into discrete classes. The underpinning of the MILVA software is the two-dimensional topographic representation of multidimensional microarray data. On this basis, the interactive MILVA functions allow a continuous exploration of microarray data driven by the direct supervision of the biologist in detecting activity patterns of co-regulated genes. AVAILABILITY: The MILVA software is freely available. The software and the related documentation can be downloaded from http://www.ncrg.aston.ac.uk/Projects/milva. User 'surrey' as username and '3245' as password to login. The software is currently available for Windows platform only.

Cluster Analysis↗

PubMed perspective of family medicine research: where does it stand?

OBJECTIVE: The aim of this study was to obtain a view of family medicine research by analyzing PubMed citations from 1960-2003. METHOD: Family practice (FP) citations in PubMed from 1960 to 2003 were downloaded in MEDLINE format. This was written into relation database using 'PubMed Grabber/Analyzer' software developed at University of Kelaniya, Sri Lanka. Search Query Language (SQL) and online PubMed queries were used for further analysis. RESULTS: There were 50288 FP citations from 80 countries. Of these, 33712 (67%) citations were from 15 FP journals. United Kingdom (18760), United States (13584), Australia (3262), Canada (1848), Germany-west (1340) were the five countries which had the most citations and 22 countries had less than 5 citations. Van Weel C (118), Geyman JP (116), Olesen F (87), Jones R (83) and Knottnerus JA (82) were numerically, the top five authors. Only 921 authors had more than 10 citations and the vast majority of authors had only one citation. Letters (5121), review (2715), editorial (2259), randomized controlled trials-RCT (1585) and Meta-analysis (44) were the top publication types. 40 citations found under 'qualitative research'. Discussion. The relatively few PubMed FP citations (50288) are by a small number of academics in developed countries. Citations showed an upsurge from the mid 1980s to the late 1990's but reached a plateau in the new millennium. Compared to PubMed citations from 1960-2003 in other specialties such as 2737655 for public health, 1151194 for cardiology & cardiovascular diseases and 318538 for medical informatics, the 50288 FP citations were paltry. Paucity of RCT (1585) and meta-analysis (44) was noted. The low 'qualitative research' citations (44) could have been due to the late introduction of the MeSH concept in 2003. CONCLUSIONS: Priority should be given to increase FP research and also to ensure the indexing of FP journals that are not currently indexed in PubMed. Efforts to increase citations in Medline may not give the desired results because of low priority given primary care specialties such as family medicine in the USA. Alternative solution of a separate bibliographic database for FP similar to PsycInfo may be too costly.

Family Practice↗

Morphology comparison of individually selected hyperactivated and non-hyperactivated human spermatozoa.

The objective of this study was to compare the morphology of human spermatozoa undergoing hyperactivated motility in vitro with those that were non-hyperactivated (non-hyp). Hyperactivation criteria were established by the Hobson Sperm Tracker (HST), sampling at 25 Hz, as curvilinear velocity (VCL) > or = 70 microns/s, amplitude of lateral head displacement (ALH) > or = 7 microns, linearity (LIN) < or = 30% and straight-line velocity (VSL) < or = 30 microns/s. Specially developed software incorporated in the HST produced a white computer-generated overlay for spermatozoa satisfying hyperactivation criteria. These spermatozoa, visually identified on a tracking monitor, were individually removed with micromanipulation equipment using a 12 microns-diameter needle. Fifty-six patient ejaculates were examined comprising a total morphological analysis of 1886 non-hyp spermatozoa and 1051 hyperactivated spermatozoa. Hyperactivated spermatozoa had a significantly higher mean percentage of normal heads and small acrosomes (P < 0.0001 and < 0.0001 respectively) and a significantly lower percentage of large and round heads, midpieces and tail defects (P = 0.002, < 0.0001, 0.02 and < 0.0001 respectively) when compared with non-hyp spermatozoa. These data demonstrate, for the first time, that a homogeneous live population of human hyperactivated spermatozoa, selected in vitro from patients with highly variable degrees of teratozoospermia, is comprised predominantly of cells with normal morphology (P < 0.0001).

Fertilization↗