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Precentral gyrus discrepancy in electronic versions of the Talairach atlas.

Electronic versions of the atlas of Talairach and Tournoux, including the Talairach Daemon and the official versions published by Thieme, contain a discrepant region of the precentral gyrus on axial slice +35 mm that extends far forward into the frontal lobe. This area is anatomically incorrect and internally inconsistent within the digital atlas software applications using their multiplanar cross-referencing tools. By cross-referencing the axial, sagittal, and coronal plates from the original printed atlas, we demonstrate that the discrepant area should be labeled middle frontal gyrus. The mislabeled portion encompasses a 3 x 1.5-cm region in the axial plane and has significant implications for sensorimotor studies that rely on the digital atlases for anatomic labeling.

Brain Mapping↗

Automated software package for icosahedral virus reconstruction.

The three-dimensional reconstruction of icosahedral viruses from electron micrograph images has become an important tool for understanding virus structure, function, and pathogenesis. We have developed an integrated suite of software programs to automate most of the operations involved in producing these reconstructions from EM images. Our package combines the analytical capabilities of preexisting algorithms together with approaches we have developed to produce an interactive working environment which enhances the efficiency and usefulness of this approach to the structural analysis of icosahedral viruses.

Algorithms↗

Facilitating knowledge maintenance of clinical guidelines and protocols.

Clinical protocols and guidelines are widely used in the medi-cal domain to improve disease management techniques. Different software systems are in development to support the de-sign and the execution of such guidelines. The bottleneck in the guideline software developing process is the transformation of the text-based clinical guidelines into a formal representation, which can be used by the execution software. This paper introduces a method and a tool that was designed to provide a solution for that bottleneck. The so-called Guideline Markup Tool (GMT) facilitates the translation of guidelines into a formal representation written in XML. This tool enables the protocol designer to create links between the original guideline and its formal representation and ease the editing of guidelines applying design patterns in the form of macros. The usefulness of our approach is illustrated using GMT to edit Asbru protocols. We performed a usability study with eight participants to examine the usefulness of the GMT and of the Asbru macros, which showed that the proposed approach is very appropriate to author and maintain clinical guidelines.

Clinical Protocols↗

Usage of the www.2aida.org AIDA diabetes software Website: a pilot study.

AIDA is a diabetes-computing program freely available from www.2aida.org on the Web. The software is intended to serve as an educational support tool, and can be used by anyone who has an interest in diabetes, whether they be patients, relatives, health-care professionals, or students. In previous "Diabetes Information Technology & WebWatch" columns various indicators of usage of the AIDA program have been reviewed, and various comments from users of the software have been documented. One aspect of AIDA, though, that has been of considerable interest has been to investigate its Web-based distribution as a wider paradigm for more general medically related usage of the Internet. In this respect we have been keen to understand in general terms: (1) why people are turning to the Web for health-care/diabetes information; (2) more specifically, what sort of people are making use of the AIDA software; and (3) what benefits they feel might accrue from using the program. To answer these types of questions we have been conducting a series of audits/surveys via the AIDA Website, and via the software program itself, to learn as much as possible about who the AIDA end users really are. The rationale for this work is that, in this way, it should be possible to improve the program as well as tailor future versions of the software to the interests and needs of its users. However, a recurring observation is that data collection is easiest if it is as unobtrusive and innocuous as possible. One aspect of learning as much as possible about diabetes Website visitors and users may be to apply techniques that do not necessitate any visitor or user interaction. There are various programs that can monitor what pages visitors are viewing at a site. As these programs do not require visitors to do anything special, over time some interesting insights into Website usage may be obtained. For the current study we have reviewed anonymous logstats data, which are automatically collected at many Websites, to try and establish a baseline level of usage for the AIDA site. For the initial pilot study the analysis was performed from October 1, 2000 to November 1, 2001. The study has yielded an interesting insight into how the AIDA Website is being used. The results also confirm those of previous audits based on different self-reported methodologies, confirming, amongst other things, what countries people are visiting from and what operating systems/computers they are using. These analyses have been informative and useful. Given this, it is proposed to repeat the current pilot survey approach on a routine basis, in the future, as a way of monitoring on-going usage of the AIDA Website.

Diabetes Mellitus↗

Why people download the freeware AIDA v4.3a diabetes software program: a proof-of-concept semi-automated analysis.

AIDA is a diabetes-computing program freely available at www.2aida.org on the Web. The software is intended to serve as an educational support tool and can be used by anyone who has an interest in diabetes, whether they be patients, relatives, health-care professionals, or students. In previous "Diabetes Information Technology & WebWatch" columns various indicators of usage of the AIDA program have been reviewed, and various comments from users of the software have been documented. The purpose of this column is to overview a proof-of-concept semi-automated analysis about why people are downloading the latest version of the AIDA educational diabetes program. AIDA permits the interactive simulation of plasma insulin and blood glucose profiles for teaching, demonstration, self-learning, and research purposes. It has been made freely available, without charge, on the Internet as a noncommercial contribution to continuing diabetes education. Since its launch in 1996 over 300,000 visits have been logged at the main AIDA Website-www.2aida.org-and over 60,000 copies of the AIDA program have been downloaded free-of-charge. This column documents the results of a semi-automated analysis of comments left by Website visitors while they were downloading the AIDA software, before they had a chance to use the program. The Internet-based survey methodology and semi-automated analysis were both found to be robust and reliable. Over a 5-month period (from October 3, 2001 to February 28, 2002) 400 responses were received. During the corresponding period 1,770 actual visits were made to the Website survey page-giving a response rate to this proof-of-concept study of 22.6%. Responses were received from participants in over 54 countries-with nearly half of these (n = 194; 48.5%) originating from the United States, United Kingdom, and Canada; 208 responses (52.0%) were received from patients with diabetes, 50 (12.5%) from doctors, 49 (12.3%) from relatives of patients, with fewer responses from students, diabetes educators, nurses, pharmacists, and other end users. The semi-automated analysis adopted for this study has re-affirmed the feasibility of using the Internet to obtain free-text comments, at no real cost, from a substantial number of medical software downloaders/users. The survey has also offered some insight into why members of the public continue to turn to the Internet for medical information. Furthermore it has provided useful information about why people are actually downloading the AIDA v4.3a interactive educational "virtual diabetes patient" simulator.

Automation↗

ScanImage: flexible software for operating laser scanning microscopes.

BACKGROUND: Laser scanning microscopy is a powerful tool for analyzing the structure and function of biological specimens. Although numerous commercial laser scanning microscopes exist, some of the more interesting and challenging applications demand custom design. A major impediment to custom design is the difficulty of building custom data acquisition hardware and writing the complex software required to run the laser scanning microscope. RESULTS: We describe a simple, software-based approach to operating a laser scanning microscope without the need for custom data acquisition hardware. Data acquisition and control of laser scanning are achieved through standard data acquisition boards. The entire burden of signal integration and image processing is placed on the CPU of the computer. We quantitate the effectiveness of our data acquisition and signal conditioning algorithm under a variety of conditions. We implement our approach in an open source software package (ScanImage) and describe its functionality. CONCLUSIONS: We present ScanImage, software to run a flexible laser scanning microscope that allows easy custom design.

Equipment Design↗

Penetrances of breast and ovarian cancer in a large series of families tested for BRCA1/2 mutations.

Accurate estimates of breast and ovarian cancer penetrance in BRCA1/2 mutation carriers are crucial in genetic counseling. Estimation is difficult because of the low frequency of mutated alleles and the often-uncertain mechanisms of family ascertainment. We estimated the penetrances of breast and ovarian cancers in carriers of BRCA1/2 mutations by maximizing the retrospective likelihood of the genetic model, given the observed test results, in 568 Italian families screened for germline mutations. The software BRCAPRO was used as a probability calculation tool in a Markov Chain Monte Carlo approach. Breast cancer penetrances were 27% (95% CI 20-34%) at age 50 years and 39% (27-52%) at age 70 in BRCA1 carriers, and 26% (0.18-0.34%) at age 50 and 44% (29-58%) at age 70 in BRCA2 carriers, and ovarian cancer penetrances were 14% (7-22%) at age 50 and 43% (21-66%) at age 70 in BRCA1 carriers and 3% (0-7%) at age 50 and 15% (4-26%) at age 70 in BRCA2 carriers. The new model gave a better fit than the current default in BRCAPRO, the likelihood being 70 log units greater; in addition, the observed numbers of mutations in families stratified by gene and by cancer profile were not significantly different from those expected. Our new penetrance functions are appropriate for predicting breast cancer risk, and for determining the probability of carrying BRCA1/2 mutations, in people who are presently referred to genetic counseling in Italy. Our approach could lead to country-customized versions of the BRCAPRO software by providing appropriate population-specific estimates.

Adult↗

SPACAR: a software subroutine package for simulation of the behavior of biomechanical systems.

Direct dynamics computer simulation is gaining importance as a research tool in the biomechanical study of complex human movements. Therefore, the need for general-purpose software packages with which the equations of motion can be derived automatically and solved numerically is growing. In this paper such a method is described: SPACAR. The method is compared to well-known commercially available software packages. On the basis of the results obtained on a test problem simulated with both SPACAR and DADS, it is concluded that both methods are accurate; DADS is much faster. The user-friendliness of SPACAR is less than that of DADS. However, SPACAR has two major advantages. First is the basic deformability of all elements, which allows handling of all kinds of problems within a unified framework; second is the full availability of the source code, which allows the experienced user to broaden the scope of possibilities to any extent.

Biomechanical Phenomena↗

Design and application of PDBlib, a C++ macromolecular class library.

PDBlib is an extensible object-oriented class library written in C++ for representing the three-dimensional structure of biological macromolecules. The software design strategy, features of many of the 129 classes currently distributed with the library, and two sample applications which use the library are described. Version 1.0 of the library represents the structural features of proteins, DNA, RNA and complexes thereof, at a level of detail on a par with that which can be parsed from a Protein Data Bank (PDB) entry. However, the memory-resident representation of the macromolecule is independent of the PDB entry and can be obtained from other sources, e.g. relational and object-oriented databases. PDBlib classes are organized into four categories: (i) classes that model the macromolecule; (ii) classes that enhance the extensibility of the library; (iii) classes that provide navigation facilities of the object-oriented macromolecular structure representation; and (iv) a class that loads a PDB file into the memory-resident object-oriented representation. A number of general-purpose procedures that return features of this representation and that are relevant to all biological disciplines are included in (i). The library has been used to develop PDBtool, a prototype structure verification tool, and PDBview, a structure rendering tool that requires no specialized graphics hardware and software. Current work centers on making the macromolecular structures represented by PDBlib persistent using a commercial object-oriented database and providing an additional class library, MMQLlib, to query those structures.

Databases, Factual↗

Eval: a software package for analysis of genome annotations.

SUMMARY: Eval is a flexible tool for analyzing the performance of gene annotation systems. It provides summaries and graphical distributions for many descriptive statistics about any set of annotations, regardless of their source. It also compares sets of predictions to standard annotations and to one another. Input is in the standard Gene Transfer Format (GTF). Eval can be run interactively or via the command line, in which case output options include easily parsable tab-delimited files. AVAILABILITY: To obtain the module package with documentation, go to http://genes.cse.wustl.edu/ and follow links for Resources, then Software. Please contact brent@cse.wustl.edu

Computational Biology↗

British Diabetic Association review of the AIDA v4 diabetes software simulator program.

AIDA is a diabetes-computing program freely available from www.2aida.org on the Web. The software is intended to serve as an educational support tool, and can be used by anyone who has an interest in diabetes, whether they be patients, relatives, health-care professionals, or students. In 1996, during the beta-testing phase of the AIDA v4 project, the British Diabetic Association (BDA)-now called Diabetes UK-was approached and offered the AIDA software by the author, without charge, as a noncommercial contribution to continuing diabetes education. The BDA undertook their own independent assessment of the program, which involved distributing AIDA to a panel of potential end-users (health-care professionals and patients). Comments were solicited regarding the utility, clarity, and perceived safety of the software from users outside the BDA, as well as from various internal assessors. As a result of the feedback, a decision was taken by the BDA to offer AIDA to health-care professionals through the BDA's health-care professional brochure. One thousand copies of the software were produced on diskette, and 1,000 copies of the BDA's version of the program's user guide-printed as a small book-were made available for distribution by post. In this Diabetes Information Technology & WebWatch column an overview is given of the anonymous feedback provided to the BDA by some of the external evaluators. Looking back, nearly 8 years after the launch of AIDA, it is interesting to review some of the comments received and compare these with what has actually happened with the software. To date over 400,000 visits have been logged at the AIDA Web pages, and over 80,000 copies of the program have been downloaded free-of-charge. It is highlighted that this widespread downloading of, and interest in, the AIDA software seems to largely have been fuelled by the program's free availability on the Internet. The use of the World Wide Web to enhance the distribution of other medical (diabetes) programs is highlighted.

Computer Simulation↗

kltool: A tool to analyze spatiotemporal complexity.

We announce the availability of a software package, called kltool, that can extract phase space information from complex spatiotemporal data via the Karhunen-Loeve analysis. Data generated by the periodic, quasiperiodic or chaotic evolution of a small number of spatially coherent structures can be processed. A key feature of kltool is that it allows the user to interact easily with the data processing and its graphical display. We illustrate the use of kltool on numerical data from the Kuramoto-Sivashinsky equation and laboratory data from a flame experiment.

Journal Article↗

Video capture virtual reality as a flexible and effective rehabilitation tool.

Video capture virtual reality (VR) uses a video camera and software to track movement in a single plane without the need to place markers on specific bodily locations. The user's image is thereby embedded within a simulated environment such that it is possible to interact with animated graphics in a completely natural manner. Although this technology first became available more than 25 years ago, it is only within the past five years that it has been applied in rehabilitation. The objective of this article is to describe the way this technology works, to review its assets relative to other VR platforms, and to provide an overview of some of the major studies that have evaluated the use of video capture technologies for rehabilitation.

Journal Article↗

C-quence: a tool for analyzing qualitative sequential data.

C-quence is a software application that matches sequential patterns of qualitative data specified by the user and calculates the rate of occurrence of these patterns in a data set. Although it was designed to facilitate analyses of face-to-face interaction, it is applicable to any data set involving categorical data and sequential information. C-quence queries are constructed using a graphical user interface. The program does not limit the complexity of the sequential patterns specified by the user.

Algorithms↗

MegaPX: fast and space-efficient peptide assignment method using IBF-based multi-indexing.

MOTIVATION: A central problem for metaproteomic analysis is the often-unknown taxonomic composition of the analyzed microbiomes. Using a database search, the standard approach requires prior knowledge of which proteins and taxa to include in the protein reference database or to use tailored metagenome-derived databases, which are expensive and error-prone in their generation. A possible strategy to circumvent this database search issue is de novo sequencing, where peptide sequences are directly identified from mass spectra. However, these sequences must still be mapped back to potentially extensive databases. Here, alignment-based approaches enable robust and precise results, with the potential drawback of high memory usage and long run times. RESULTS: We present MegaPX, a software for rapidly classifying de novo peptide sequences against large protein databases. MegaPX implemented as a C++-based tool, uses an alignment-free, k-mer approach as a taxonomic classification method with the possibility of generating mutated reference databases for error-tolerant searching. It uses various algorithms, including interleaved Bloom filters, to efficiently compute approximate membership queries, ensuring fast processing times while querying and indexing large databases in a multi-indexing fashion. We demonstrate the potential of MegaPX by analyzing different samples, including metaproteomics, against extensive reference databases, highlighting its use as a fast screening tool.

Software↗

Immediate and delayed memory tasks: a computerized behavioral measure of memory, attention, and impulsivity.

The Immediate and Delayed Memory Task (IMT/DMT), a variant of the Continuous Performance Test (CPT), is a new software package designed to be a flexible research tool for the study of attention, memory, and impulsivity. This package allows researchers to determine the design to be used during a testing session and to manipulate many of the parameters. It features two components: the IMT and the DMT, both of which present sequential 2- to 7-digit stimuli with variable presentation rates and intertrial intervals. Subjects respond to identically matched stimuli presented consecutively, spanning a brief period of time (IMT), or to stimuli spanning a greater period of time (during which intervening stimuli to be ignored appear; DMT). Task complexity can be adjusted to suit applications for both children and adults. Preliminary studies have demonstrated that these laboratory tasks are sensitive to group differences, produce stable baselines of performance, and are sensitive to drug-induced performance decrements.

Attention↗

Immunoinformatics comes of age.

With the burgeoning immunological data in the scientific literature, scientists must increasingly rely on Internet resources to inform and enhance their work. Here we provide a brief overview of the adaptive immune response and summaries of immunoinformatics resources, emphasizing those with Web interfaces. These resources include searchable databases of epitopes and immune-related molecules, and analysis tools for T cell and B cell epitope prediction, vaccine design, and protein structure comparisons. There is an agreeable synergy between the growing collections in immune-related databases and the growing sophistication of analysis software; the databases provide the foundation for developing predictive computational tools, which in turn enable more rapid identification of immune responses to populate the databases. Collectively, these resources contribute to improved understanding of immune responses and escape, and evolution of pathogens under immune pressure. The public health implications are vast, including designing vaccines, understanding autoimmune diseases, and defining the correlates of immune protection.

Amino Acid Sequence↗

[Crystallography of drug polymorphism: emergence of new resolution methods and prediction of crystalline structures].

For the pharmaceutical and agrochemical industries, reducing development time is currently a primary objective to accelerate the marketing of new products. In-depth solid-state characterization is an essential element in achieving this performance. For this purpose, it is now recognized that, in a department of solid-state physical characterization, theoretical approaches have to be integrated with experimental tools. Benefiting from the constant improvement in computer hardware and software in terms of computing powers and algorithm development, these approaches appear to be a complementary method that can help explain and rationalize experimental data. In recent years, with the help of both molecular modeling tools and crystallographic databases, original methods have been developed and successfully applied to systems of variable complexity. The X-ray diffraction crystal structure determination makes it possible to calibrate the force field and to adapt it more precisely to the compound studied, thereby reducing one of the sources of uncertainty. Although crystal structures are preferentially determined from single crystal data, it has been recently shown that powder diffraction data can also be used when single crystals are missing. Therefore, the different benefits of such an approach are the following: ab initio predictive study of crystalline polymorphism, molecular packing analysis and detection of cleavage planes, prediction of morphology in vacuum. In conjunction with crystallite preferred orientation observed in powder patterns, grinding effects on the crystal habit and solvent effects in modifying growth can be clearly understood. Selected industrial cases exemplify the operational application of this methodology.

Crystallization↗