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Relationship between prevalence rate ratios and odds ratios in cross-sectional studies.

BACKGROUND: Cross-sectional data are frequently encountered in epidemiology and published results are predominantly presented in terms of prevalence odds ratios (POR). A recent debate suggested a switch from POR, which is easily obtained via logistic regression analysis available in many statistical packages, to prevalence rate ratios (PRR). We thought it useful to explore the mathematical relationship between PRR and POR and to evaluate the degree of divergence of the two measures as a function of the prevalence of disease and exposure. METHODS: With the use of some algebra and the common definitions of prevalence of the disease (Pr(D)), prevalence of the exposure (Pr(E)), PRR, and POR in a 2 x 2 table, we have identified a useful formula that represents the mathematical relationship between these four quantities. Plots of POR versus PRR for selected values of Pr(D) and Pr(E) are reported. RESULTS: Mathematically speaking the general relationship takes the form of a second order curve which can change curvature and/or rotate around the point POR = PRR = 1 according to the values of Pr(D) and Pr(E), with POR being always further from the null value than is PRR. The discrepancies are much more influenced by variations in Pr(D) than in Pr(E). CONCLUSIONS: We think that the choice between POR or PRR in a cross-sectional study ought to be based on epidemiological grounds and not on the availability of software tools. The paper offers a formula and some-examples for a better understanding of the relationship between PRR and POR as a function of the prevalence of the disease and the prevalence of the exposure.

Cross-Sectional Studies↗

Knowledge-based simulation of genetic regulation in bacteriophage lambda.

We have developed a general-purpose computer program for the functional simulation of regulatory genetics. This simulator is knowledge-based and was developed using the Unit System, a software tool for the acquisition, representation, and manipulation of hierarchically organized knowledge. The advantages of a knowledge-based design are presented, and the simulator's architecture is described. Its performance on the decision between lytic and lysogenic growth in Bacteriophage Lambda is reported.

Bacteriophage lambda↗

Back-propagation and counter-propagation neural networks for phylogenetic classification of ribosomal RNA sequences.

A neural network system has been developed for rapid and accurate classification of ribosomal RNA sequences according to phylogenetic relationship. The molecular sequences are encoded into neural input vectors using an n-gram hashing method. A SVD (singular value decomposition) method is used to compress and reduce the size of long and sparse n-gram input vectors. The neural networks used are three-layered, feed-forward networks that employ supervised learning paradigms, including the back-propagation algorithm and a modified counter-propagation algorithm. A pedagogical pattern selection strategy is used to reduce the training time. After trained with ribosomal RNA sequences of the RDP (Ribosomal Database Project) database, the system can classify query sequences into more than one hundred phylogenetic classes with a 100% accuracy at a rate of less than 0.3 CPU second per sequence on a workstation. When compared to other sequence similarity search methods, including Similarity Rank, Blast and Fasta, the neural network method has a higher classification accuracy at a speed of about an order of magnitude faster. The software tool will be made available to the biology community, and the system may be extended into a gene identification system for classifying indiscriminately sequenced DNA fragments.

Algorithms↗

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↗

UK CropNet: a collection of databases and bioinformatics resources for crop plant genomics.

The UK Crop Plant Bioinformatics Network (UK CropNet) was established in 1996 in order to harness the extensive work in genome mapping in crop plants in the UK. Since this date we have published five databases from our central UK CropNet WWW site (http://synteny.nott.ac.uk/) with a further three to follow shortly. Our resource facilitates the identification and manipulation of agronomically important genes by laying a foundation for comparative analysis among crop plants and model species. In addition, we have developed a number of software tools that facilitate the visualisation and analysis of our data. Many of our tools are made freely available for use with both crop plant data and with data from other species.

Crops, Agricultural↗

HyPaLib: a database of RNAs and RNA structural elements defined by hybrid patterns.

The database, called HyPaLib (for Hybrid Pattern Library), contains annotated structural elements characteristic for certain classes of structural and/or functional RNAs. These elements are described in a language specifically designed for this purpose. The language allows convenient specification of hybrid patterns, i.e. motifs consisting of sequence features and structural elements together with sequence similarity and thermodynamic constraints. We are currently developing software tools that allow a user to search sequence databases for any pattern in HyPaLib, thus providing functionality which is similar to PROSITE, but dedicated to the more complex patterns in RNA sequences. HyPaLib is available at http://bibiserv. techfak.uni-bielefeld.de/HyPa/.

Algorithms↗

CSDBase: an interactive database for cold shock domain-containing proteins and the bacterial cold shock response.

CSDBase (http://www.chemie.uni-marburg.de/~csdbase/) is an interactive Internet-embedded research platform providing detailed information on proteins containing the cold shock domain (CSD). It consists of two separated database cores, one dedicated to CSD protein information, and one to provide a powerful resource to relevant literature with emphasis on the bacterial cold shock response. In addition to detailed protein information and useful cross links to other web sites, CSDBase contains computer-generated CSD structure models for most CSD-containing protein sequences available at NCBI non-redundant protein database at the time of CSDBase establishment. These models were calculated on the basis of known crystal and/or NMR structures using SWISS-MODEL and can be downloaded as PDB structure coordinate files for viewing and for manipulation with other software tools. CSDBase will be regularly updated and is organized in a compact form providing user friendly interfaces to both database cores which allow for easy data retrieval.

Amino Acid Sequence↗

EcoCyc: a comprehensive database resource for Escherichia coli.

The EcoCyc database (http://EcoCyc.org/) is a comprehensive source of information on the biology of the prototypical model organism Escherichia coli K12. The mission for EcoCyc is to contain both computable descriptions of, and detailed comments describing, all genes, proteins, pathways and molecular interactions in E.coli. Through ongoing manual curation, extensive information such as summary comments, regulatory information, literature citations and evidence types has been extracted from 8862 publications and added to Version 8.5 of the EcoCyc database. The EcoCyc database can be accessed through a World Wide Web interface, while the downloadable Pathway Tools software and data files enable computational exploration of the data and provide enhanced querying capabilities that web interfaces cannot support. For example, EcoCyc contains carefully curated information that can be used as training sets for bioinformatics prediction of entities such as promoters, operons, genetic networks, transcription factor binding sites, metabolic pathways, functionally related genes, protein complexes and protein-ligand interactions.

Computational Biology↗

Tests of rRNA hybridization to microarrays suggest that hybridization characteristics of oligonucleotide probes for species discrimination cannot be predicted.

Hybridization of rRNAs to microarrays is a promising approach for prokaryotic and eukaryotic species identification. Typically, the amount of bound target is measured by fluorescent intensity and it is assumed that the signal intensity is directly related to the target concentration. Using thirteen different eukaryotic LSU rRNA target sequences and 7693 short perfect match oligonucleotide probes, we have assessed current approaches for predicting signal intensities by comparing Gibbs free energy (DeltaG degrees) calculations to experimental results. Our evaluation revealed a poor statistical relationship between predicted and actual intensities. Although signal intensities for a given target varied up to 70-fold, none of the predictors were able to fully explain this variation. Also, no combination of different free energy terms, as assessed by principal component and neural network analyses, provided a reliable predictor of hybridization efficiency. We also examined the effects of single-base pair mismatch (MM) (all possible types and positions) on signal intensities of duplexes. We found that the MM effects differ from those that were predicted from solution-based hybridizations. These results recommend against the application of probe design software tools that use thermodynamic parameters to assess probe quality for species identification. Our results imply that the thermodynamic properties of oligonucleotide hybridization are by far not yet understood.

Animals↗

Analysis of structural and physico-chemical parameters involved in the specificity of binding between alpha-amylases and their inhibitors.

Enzyme-inhibitor specificity was studied for alpha-amylases and their inhibitors. We purified and cloned the cDNAs of two different alpha-amylase inhibitors from the common bean (Phaseolus vulgaris) and have recently cloned the cDNA of an alpha-amylase of the Mexican bean weevil (Zabrotes subfasciatus), which is inhibited by alpha-amylase inhibitor 2 but not by alpha-amylase inhibitor 1. The crystal structure of AI-1 complexed with pancreatic porcine alpha-amylase allowed us to model the structure of AI-2. The structure of Zabrotes subfasciatus alpha-amylase was modeled based on the crystal structure of Tenebrio molitor alpha-amylase. Pairwise AI-1 and AI-2 with PPA and ZSA complexes were modeled. For these complexes we first identified the interface forming residues. In addition, we identified the hydrogen bonds, ionic interactions and loss of hydrophobic surface area resulting from complex formation. The parameters we studied provide insight into the general scheme of binding, but fall short of explaining the specificity of the inhibition. We also introduce three new tools-software packages STING, HORNET and STINGPaint-which efficiently determine the interface forming residues and the ionic interaction data, the hydrogen bond net as well as aid in interpretation of multiple sequence alignment, respectively.

Amino Acid Sequence↗

Induced radioactivity in the forward shielding and semiconductor tracker of the ATLAS detector.

The radioactivity induced in the forward shielding, copper collimator and semiconductor tracker modules of the ATLAS detector has been studied. The ATLAS detector is a long-term experiment which, during operation, will require to have service and access to all of its parts and components. The radioactivity induced in the forward shielding was calculated by Monte Carlo methods based on GEANT3 software tool. The results show that the equivalent dose rates on the outer surface of the forward shielding are very low (at most 0.038 microSv h(-1)). On the other hand, the equivalent dose rates are significantly higher on the inner surface of the forward shielding (up to 661 microSv h(-1)) and, especially, at the copper collimator close to the beampipe (up to 60 mSv h(-1)). The radioactivity induced in the semiconductor tracker modules was studied experimentally. The module was activated by neutrons in a training nuclear reactor and the delayed gamma ray spectra were measured. From these measurements, the equivalent dose rate on the surface of the semiconductor tracker module was estimated to be < 100 microSv h(-1) after 100 d of Large Hadron Collider (LHC) operation and 10 d of cooling.

Construction Materials↗

Knowledge-based computer systems for radiotherapy planning.

Radiation therapy is one of the first areas of clinical medicine to utilize computers in support of routine clinical decision making. The role of the computer has evolved from simple dose calculations to elaborate interactive graphic three-dimensional simulations. These simulations can combine external irradiation from megavoltage photons, electrons, and particle beams with interstitial and intracavitary sources. With the flexibility and power of modern radiotherapy equipment and the ability of computer programs that simulate anything the machinery can do, we now face a challenge to utilize this capability to design more effective radiation treatments. How can we manage the increased complexity of sophisticated treatment planning? A promising approach will be to use artificial intelligence techniques to systematize our present knowledge about design of treatment plans, and to provide a framework for developing new treatment strategies. Far from replacing the physician, physicist, or dosimetrist, artificial intelligence-based software tools can assist the treatment planning team in producing more powerful and effective treatment plans. Research in progress using knowledge-based (AI) programming in treatment planning already has indicated the usefulness of such concepts as rule-based reasoning, hierarchical organization of knowledge, and reasoning from prototypes. Problems to be solved include how to handle continuously varying parameters and how to evaluate plans in order to direct improvements.

Artificial Intelligence↗

Quantification of global and regional ventricular function in cardiac magnetic resonance imaging.

One of the strong assets of cardiac magnetic resonance (CMR) is its ability to assess myocardial anatomy, structure, function, flow, and perfusion within a single examination. Quantification of global and regional function from magnetic resonance imaging (MRI) studies was shown to be accurate and reproducible in experimental and clinical research studies. With the advent of high-performance MRI scanners and newly developed pulse sequences, image acquisition times have been reduced considerably in recent years. However, the clinical use of CMR remains limited for various reasons. Among these limitations is that the amount of images obtained in a typical cardiac examination is so large that visual and especially quantitative image analysis is tedious and time consuming. There is an urgent need for optimized dedicated software tools featuring highly automated contour detection and optimized display capabilities to present the quantitative results to the physician in an orderly fashion, thus facilitating clinical decision making. This article focuses on the state of the art in CMR postprocessing techniques for quantitative assessment of global and regional function.

Female↗

Computer-aided learning--a solution for the training needs of users & maintainers of medical equipment.

It can be argued that the strategic role of training and assessment in the use and maintenance of medical equipment for the delivery of safe and efficient healthcare is underestimated. While there has been frequent comment on this issue, the resources provided for this activity are most often insufficient. New methods are required to deliver regular, cost-effective training within the working environment, at the time and place of need. Similarly, the administrative workload has to be automated--and thus reduced--if training is to improve in both frequency and content. Computer-aided learning has had increasing and diverse application in education and training over the past few decades. The sophistication of software tools and the reduced cost of the necessary hardware makes this a viable and appropriate method for application in the field of Clinical Engineering. However, this technology has not yet been fully exploited to provide instruction in the use and maintenance of equipment. In this paper, it is proposed that computer-based training packages should not only be a source of interactive instruction and assessment, but also act as rapidly accessible reference materials or simulators of the actual device for the purpose of fault finding or troubleshooting. Brief details of a sample package are given for training in the use and maintenance of the Siemens Elema Servo Ventilator 900C.

Biomedical Engineering↗

Radiographic evaluation of dental implants with different surface treatments: an experimental study in dogs.

PURPOSE: The aim of the study was to radiographically measure the bone density at the peri-implant region after osseointegration and to compare the relative bone density achieved by different surface-treated implants. MATERIALS AND METHODS: Four different types of implant surfaces were compared, using five young-adult male mongrel dogs. The first, second, third, and fourth lower premolars were extracted. Ninety days after removal, four 3.75-mm diameter and 10-mm long screw implants (Paragon) were placed with different surface treatments in the lower hemiarches. The dogs received two implants each of the following surface treatments: 1) smooth (machined); 2) titanium plasma spray: 3) hydroxyapatite coating; and 4) sandblasting with soluble particles. The implants were maintained unloaded for 90 days. After this period, the animals were killed and the hemimandibles were extracted and radiographed. The grey level of the bone adjacent to implants was measured with a specific software tool (line histogram) and the relative bone density was calculated. RESULTS: The four different surface treatments promote different numeric levels of bone density around the dental implants (sandblasting with soluble particles, 52.45 +/- 2.95; titanium plasma spray, 53.98 +/- 3.67; machined, 55.78 +/- 3.06, and hydroxyapatite coating, 58.2 +/- 2.71). Therefore, the implants can be ranked in terms of relative bone density from high to low as follows: sandblasting with soluble particles, titanium plasma spray, machined, and hydroxyapatite coating. There were no statistically significant differences in bone density among the four groups (P = 0.1130, analysis of variance). CONCLUSION: Surface treatments that add roughness to the implant show numerically higher bone density when compared with machined surfaces. The findings of radiographic density analysis suggest that the soluble blasting media-treated surface provides a greater bone density at the peri-implant region.

Animals↗

Plastic surgeon's life: marvelous for mind, exhausting for body.

Surgery is accepted as one of the most demanding professions that create both physical and mental strain on the performers. Therefore, the authors aimed to elucidate the mental burden of surgeons, which is dedicated to operative stress. They also tested the hypotheses that participating in surgery creates mental stress on surgeons that leads to cardiovascular changes, and that this stress is more pronounced for actual operators than for first assistants. The method chosen for this purpose was an analysis of heart rate variability. Twelve surgeons (five plastic surgery staff and seven plastic surgery residents) were monitored by a digital ambulatory Holter recorder on at least two occasions. Half of the recordings were carried out on operating days and the other half on office days. Heart rate variability indices (low frequency, high frequency, high frequency/low frequency ratio, and heart rate) were analyzed from those recordings using computerized research tool software. The heart rate variability indices of the operators showed statistically significant differences between operating days and office hours in favor of an increased sympathetic and decreased parasympathetic activity for the former. For first assistants, three of the parameters, with the exception of heart rate, changed in favor of a sympathetic predominance over parasympathetic activity; these changes were also statistically significant. These results showed a sympathetic hyperactivity for both operators and first assistants during the operations. When the sympathovagal balance of the actual operators was compared with that of assistants, the former group showed a more pronounced sympathetic arousal. This difference is accepted as a proof for the mental stress of the surgery being the main factor responsible for the sympathetic hyperactivity that we detected during the operations. Surgeons continuously face a unique mental strain that other professions rarely bring forth, and these psychological stressors are associated with alterations in cardiac autonomic control that may contribute to the development of cardiac disease. Prolonged sympathetic hyperactivity could anticipate cardiac discomfort in more experienced surgeons with marginal cardiac reserve. Such cardiac diseases would be reconsidered as occupation-related illnesses, which might be reimbursed to the physician. In addition, the legal responsibility of surgeons concerning their unfavorable results might be assessed with more understanding with a realization of their undue working conditions.

Adult↗

Effect of varying slice thickness on coronary calcium scoring with multislice computed tomography in vitro and in vivo.

OBJECTIVES: To compare coronary calcium scoring results (calcium volume, calcium mass, Agatston score, and number of lesions) of different slice thicknesses using a 16-slice CT (MSCT) scanner. MATERIALS AND METHODS: A nonmoving anthropomorphic thorax phantom with calcium cylinders of different sizes and densities was scanned 30 times with repositioning applying a standardized retrospectively ECG-gated MSCT (SOMATOM Sensation 16; Siemens, Forchheim, Germany) scan protocol: collimation 12 x 0.75 mm, tube voltage 120 kV, effective tube current time-product 133 mAs(eff). Fifty patients (29 male; age 57.2 +/- 8.4 years) underwent a nonenhanced scan applying the same scan protocol. Two image sets (effective slice thicknesses 3 mm and 1 mm) were reconstructed at 60% of the RR interval. Image noise was measured in both studies. Calcium volume, calcium mass and Agatston score were calculated using a commercially available software tool. RESULTS: Due to increased image noise in thinner slices, calcium scoring in all scans was performed applying a scoring threshold of 350 HU. In the phantom study, 1-mm slices showed significantly higher scoring results in respect to calcium volume (+8.2%), calcium mass (+12.5%), and Agatston score (+5.3%) (all P < 0.0001). In the patient study, 27 patients had coronary calcifications in 3-mm slices, and 31 patients had coronary calcifications in 1-mm slices. Thinner slices showed significantly higher scoring results in respect to volume (+47.1%), mass (+47.2%), and Agatston score (+29.7%) (all P < 0.0001). CONCLUSIONS: When comparing 3-mm and 1-mm slices in coronary calcium scoring in MSCT, thinner slices lead to significantly increased scoring results.

Aged↗

Relevance of image fusion with MRI for the interpretation of I-123 iodo-methyl-tyrosine scans in patients with suspected recurrent or residual brain tumor.

PURPOSE: The aim of the study was to investigate the impact of MR/SPECT image fusion on the interpretation of I-123 iodo-methyl-tyrosine (IMT) SPECT examinations in patients with pretreated brain tumors. MATERIAL AND METHODS: In this retrospective study, 45 consecutive patients with suspected recurrent/residual gliomas (n = 41) or cerebral metastases (n = 4) were included. SPECT studies were performed using a triple-head gamma-camera system 10 minutes after injection of 300 to 370 MBq (8.1-10 mCi) I-123 IMT. Concerning MR, T1-, T2-, and FLAIR-weighted sequences as well as contrast-enhanced T1-weighted sequences were acquired by 1.5-T or 3.0-T scanners. For image fusion, the MPI-tool software package was used. SPECT and MR/SPECT fusion images were anonymized and then independently evaluated by 3 observers aware of the clinical data. Tumor localization and extent were evaluated and correlated with histopathology or clinical follow up, including MR imaging. RESULTS: In 10 of 45 (22%) patients, image fusion had a significant impact on the interpretation of scans: 5 suspected SPECT findings were correctly classified as physiological or therapy-related; in another 5 patients, image fusion added relevant clinical information on tumor extent (infiltration of the contralateral hemisphere n = 3, infiltration of the brain stem n = 2). CONCLUSIONS: According to our data, image fusion is crucial for the interpretation of positive I-123 IMT SPECT findings.

Adolescent↗