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Biomedical subjects

P L Miller

Publications and source records attributed to P L Miller.

At least 19 recordsLinked to original sources
PubMed1999

Olfactory Receptor Database: a database of the largest eukaryotic gene family.

The Olfactory Receptor Database (ORDB) is a WWW-accessible database that stores data on Olfactory Receptor-like molecules (ORs) and has been open to the public since June 1996. It contains a public and a private area. The public area includes published DNA and protein sequence data for ORs, links to OR models and data on their expression, chromosomal localization and source organism, as well as (i) links to bibliography through PubMed and (ii) interactive WWW-based tools, such as BLAST homology searching. The private area functions as a service to laboratories that are actively cloning receptors. Source laboratories enter the sequences of the receptor clones they have characterized to the private database and can search for identical or near identical OR sequences in both public and private databases. If another laboratory has cloned and deposited an identical or closely matching sequence there are means for communication between the laboratories to help avoid duplication of work. ORDB is available via the WWW at http://crepe.med.yale.edu/ORDB/HTML

Animals↗
PubMed1999

Using semantic constraints to help verify the completeness of a computer-based clinical guideline for childhood immunization.

The paper describes Commander, a prototype computer program designed to help verify the completeness of a computer-based clinical practice guideline built using if then rules. It also describes the application of Commander to a guideline for childhood immunization. Commander is designed to help identify incomplete rule sets, where there are clinically meaningful conditions to which the guideline does not respond. To allow this, the user defines semantic constraints, in the form of if-then statements, which indicate combinations of conditions which are not meaningful. In an iterative process, Commander takes the guideline rules, together with an increasingly refined set of constraints and helps focus in on any combinations of conditions to which the guideline does not respond. When applied to the clinical guideline for childhood immunization, Commander was able to dramatically reduce the number of potential combinations of conditions for consideration and also identified several areas of incompleteness in the rules.

Child↗
PubMed1998

Database tools for integrating and searching membrane property data correlated with neuronal morphology.

A critical problem in neuroscience is the lack of database tools for integrating neuronal property data. We report here the development of a combined object oriented-relational database (NeuronDB, http://senselab.med.yale.edu/neurondb) that meets these needs by providing tools for integrating data within neurons and comparing data across neurons. It focuses on three types of neuronal properties voltage-gated channels, neurotransmitter receptors, and neurotransmitters. The data are organized in relation to different regions of neurons as represented in canonical forms; using simple canonical models of complex cells as a vehicle for indexing information permits the database to be searchable across different neurons. Using these multidimensional search tools, users can locate specific properties in specific regions of a neuron; obtain integrated summaries of all properties within a region; and carry out searches to compare properties across equivalent compartments in different neurons. These tools thus permit searches of the multidimensional neuron property space equivalent to homology searches of sequence databases. NeuronDB is accessible over the Internet; it provides immediate links to citation indexes and abstracts supporting the deposited data, and annotations that indicate the state of acceptance of the data. Users are encouraged to contribute data. The ability to input the data from NeuronDB directly to NEURON and GENESIS is being developed. As a shared Web resource, NeuronDB should enhance the efforts of neuroscientists and neuronal modellers to analyze and compare the functional operations of different types of neurons.

Automation↗
PubMed1998

Tools for immunization guideline knowledge maintenance. II. Automated Web-based generation of user-customized test cases.

IMM/Test is a prototype software tool built to generate test cases that can be used to help test and verify the internal logic of an immunization forecasting program. A forecasting program takes as input a child's immunization history and produces recommendations as to which vaccinations are due and which should be scheduled next. IMM/Test was developed to test a specific immunization forecasting program, IMM/Serve. In addition, IMM/Test has been incorporated into a broader Web-based tool, IMM/Web, which allows the user (e.g., a member of an immunization registry staff) to customize the parameters used for immunization forecasting (e.g., the minimum ages for each dose and the minimum wait intervals between doses) to reflect local practice. IMM/Web then generates a customized set of test cases that may be used to test the user's immunization forecasting program. The user may also request that the test cases be automatically passed to IMM/Serve to analyze using the newly defined parameters. The paper describes the internal design of IMM/Test and IMM/Web and discusses certain lessons learned in the implementation of the two programs.

Adolescent↗
PubMed1998

Tools for immunization guideline knowledge maintenance. I. Automated generation of the logic "kernel" for immunization forecasting.

IMM/Def is a prototype computer program designed to facilitate the building and maintenance of a rule-based program which performs childhood immunization forecasting. An immunization forecasting program takes as input a child's immunization history and produces recommendations as to which vaccinations are due and which should be scheduled next. A significant amount of the knowledge required for immunization forecasting can be expressed in tabular form, including the parameters that indicate the minimum age when each dose may be given and the minimum intervals between doses. The choice of which of these sets of parameters apply to a particular case depends upon additional clinical logic. To perform forecasting, this logic must be applied in three temporal contexts: (1) a dose is due now, (2) a dose is not yet due, and (3) a dose must be scheduled to follow a dose which is due now. Building and maintaining this logic by hand is a formidable challenge. IMM/Def demonstrates how this task can be simplified by first defining immunization "definition logic" which can be automatically translated into if-then rules for each of the three contexts. The approach has been applied successfully to the six childhood vaccination series which are routinely administered. A key advantage is that IMM/Def allows one to have two specifications of the logic that can be examined independently and that can be cross-checked to help assure completeness, consistency, and accuracy of the logic. The paper describes how IMM/Def performs its translation and discusses several design issues and lessons learned.

Child↗
PubMed1998

The Human Brain Project: neuroinformatics tools for integrating, searching and modeling multidisciplinary neuroscience data.

What is neuroinformatics? What is the Human Brain Project? Why should you care? Supported by a consortium of US funding agencies, the Human Brain Project aims to bring to the analysis of brain function the same advantages of Internet-accessible databases and database tools that have been crucial to the development of molecular biology and the Human Genome Project. The much greater complexity of neural data, however, makes this a far more challenging task. As a pilot project in this new initiative, we review some of the progress that has been made and indicate some of the problems, challenges and opportunities that lie ahead.

Brain↗
PubMed1998

Issues in accommodating national changes and local variation in a computer-based guideline for childhood immunization and in related knowledge maintenance tools.

As clinical practice guidelines are increasingly implemented in computer-based form, a major challenge will be to maintain their domain knowledge as new national recommendations are developed and as local customization is required. This maintenance may also need to be performed for any computer-based tools developed to help in the guideline knowledge maintenance process itself. This paper uses the domain of childhood immunization to explore certain issues involved. It describes 1) two recent changes to the national recommendations dealing with the DTP and Polio vaccine series, and 2) several customizations requested by the immunization registries of the State of Oregon and the US Indian Health Service. It then describes how these guideline practice variations are currently handled in three computer-based tools, IMM/Serve, IMM/Def, and IMM/Test. Finally, it discusses how the use of these tools can provide one approach to characterizing the complexity of guideline variations.

Artificial Intelligence↗
PubMed1997

Podocyte loss and progressive glomerular injury in type II diabetes.

Kidney biopsies from Pima Indians with type II diabetes were analyzed. Subjects were classified clinically as having early diabetes (n = 10), microalbuminuria (n = 17), normoalbuminuria, despite a duration of diabetes equal to that of the subjects with microalbuminuria (n = 12), or clinical nephropathy (n = 12). Subjects with microalbuminuria exhibited moderate increases in glomerular and mesangial volume when compared with those with early diabetes, but could not be distinguished from subjects who remained normoalbuminuric after an equal duration of diabetes. Subjects with clinical nephropathy exhibited global glomerular sclerosis and more prominent structural abnormalities in nonsclerosed glomeruli. Marked mesangial expansion was accompanied by a further increase in total glomerular volume. Glomerular capillary surface area remained stable, but the glomerular basement membrane thickness was increased and podocyte foot processes were broadened. Broadening of podocyte foot processes was associated with a reduction in the number of podocytes per glomerulus and an increase in the surface area covered by remaining podocytes. These findings suggest that podocyte loss contributes to the progression of diabetic nephropathy.

Adult↗
PubMed1997

Combining tabular, rule-based, and procedural knowledge in computer-based guidelines for childhood immunization.

IMM/Serve is a computer program which implements the clinical guidelines for childhood immunization. IMM/Serve accepts as input a child's immunization history. It then indicates which vaccinations are due and which vaccinations should be scheduled next. The clinical guidelines for immunization are quite complex and are modified quite frequently. As a result, it is important that IMM/Serve's knowledge be represented in a format that facilitates the maintenance of that knowledge as the field evolves over time. To achieve this goal, IMM/Serve uses four representations for different parts of its knowledge base: (1) Immunization forecasting parameters that specify the minimum ages and wait-intervals for each dose are stored in tabular form. (2) The clinical logic that determines which set of forecasting parameters applies for a particular patient in each vaccine series is represented using if-then rules. (3) The temporal logic that combines dates, ages, and intervals to calculate recommended dates, is expressed procedurally. (4) The screening logic that checks each previous dose for validity is performed using a decision table that combines minimum ages and wait intervals with a small amount of clinical logic. A knowledge maintenance tool, IMM/Def, has been developed to help maintain the rule-based logic. The paper describes the design of IMM/Serve and the rationale and role of the different forms of knowledge used.

Age Factors↗
PubMed1997

Using explicitly represented biological relationships for database navigation and searching via the World-Wide Web.

MOTIVATION: The increasing availability of biological databases on the World-Wide Web and hypertext links between them has made a wealth of information easily accessible to biologists. Additional retrieval capabilities can be achieved by storing explicitly specified biological relationships between different entities as discrete database entries. RESULTS: We have built CySPID, a prototype database about the cytoskeleton that explores the approach of explicitly representing biological relationships. The stored relationships are displayed along with other retrieved information, can be used to make hyperlinks to related entities, and can be used to search for entities with specified properties. CySPID is extensible in that new types of relationships may be created without altering the database schema. AVAILABILITY: CySPID is available for public use (http://ycmi.med.yale.edu/cyspid/). The CGI scripts used by CySPID are available upon request.

Animals↗
PubMed1997

Olfactory receptor database (ORDB): a resource for sharing and analyzing published and unpublished data.

An olfactory receptor database (ORDB) is being developed to facilitate analysis of this large gene family. ORDB currently contains over 400 olfactory receptor sequences and related information, and is available via the World Wide Web. We plan to incorporate functional data, structural models, spatial localization and other categories of information, toward an integrated model of olfactory receptor function.

Amino Acid Sequence↗
PubMed1997

Visualizing the logic of a clinical guideline: a case study in childhood immunization.

IMM/Graph is a visual model designed to help knowledge-base developers understand and refine the guideline logic for childhood immunization. The IMM/Graph model is domain-specific and was developed to help build a knowledge-based system that makes patient-specific immunization recommendations. A "visual vocabulary" models issues specific to the immunization domain, such as (1) the age a child is first eligible for each vaccination dose, (2) recommended, "past due" and maximum ages, (3) minimum waiting periods between doses, (4) the vaccine brand or preparation to be given, and (5) the various factors affecting the time course of vaccination. Several lessons learned in the course of developing IMM/Graph include the following: (1) The intended use of the model may influence the choice of visual presentation; (2) There is a potentially interesting interplay between the use of visual and textual information in creating the visual model; (3) Visualization may help a development team better understand a complex clinical guideline and may also help highlight areas of incompleteness.

Child, Preschool↗
PubMed1997

A prototype Web site for immunization knowledge maintenance.

IMM/Web is a prototype Web site designed to assist in the maintenance of the knowledge required to perform computer-based forecasting for childhood immunization. IMM/Web operates in conjunction with IMM/Serve, a immunization forecasting program that takes a child's immunization history and produces recommendations as to which vaccinations are due, and which should be scheduled next. IMM/Serve's domain knowledge is expressed in both tabular and rule-based form. Using IMM/Web, the various tabular forecasting parameters can be modified via the Web. Test cases can then be generated automatically which can be used to help verify the new version of logic. Finally, the test cases can be automatically passed for IMM/Serve to analyze using the newly defined parameters. The IMM/Web project is exploring how the process of updating, customizing, and testing new versions of a computer-based clinical guideline might be performed and guided in an organized fashion via the World-Wide Web.

Child↗
PubMed1996

Molecular genetic analysis of sperm competition in the damselfly Ischnura elegans (Vander Linden).

Sperm competition can be a powerful selective force in the evolution of mating systems. Several odonate species have attracted study to assess the extent and mechanism of last-male sperm precedence. Members of the genus Ischnura (Zygoptera) display a particularly interesting range of mating systems, and Ischnura elegans was selected for study. Polymorphic microsatellites were cloned, sequenced and used to determine paternity of I. elegans larvae, to reveal patterns of sperm precedence. More than 3000 larvae, collected from both wild and captively bred I. elegans females, were typed for one or two microsatellite loci and paternity was determined by comparison with parental genotypes. Microsatellite typing showed that most wild-caught females had mated with several males. Analysis of offspring from females which mated in captivity showed that multiple-matings result in a large proportion of last-male sperm precedence (mean value for immediate last male precedence is 0.79 +/- 0.2 (+/- s.d.; n = 11, range = 0.44-1)). There is appreciable variation in the extent and patterns of immediate and longer-term precedence, which could reflect differences in male sperm removal ability or selective use of sperm by females.

Animals↗
PubMed1996

IMM/Serve: a rule-based program for childhood immunization.

A rule-based program, IMM/Serve, is being developed to help guide childhood immunization for initial use, within Oregon. The program is designed primarily for automated use with an online immunization registry, but can also be used interactively by a single user. The paper describes IMM/Serve and discusses 1) the sources of complexity in immunization logic, 2) the potential advantages of a rule-based approach for representing that logic, and 3) the potential advantage of such a program evolving to become the standard of care. Related projects include 1) a computer-based tool to help verify the completeness of the logic, 2) a tool that allows a central part of the logic to be generated automatically, and 3) an approach that allows visualization of the logic graphically.

Child↗
PubMed1995

Biomechanical evaluation of cervical spine stabilization methods using a porcine model.

STUDY DESIGN: The biomechanical stability of three different methods of cervical spine stabilization was evaluated in a porcine model. Specimens were tested in flexion, extension, and axial rotation. OBJECTIVES: Our goal was to determine if posterior lateral mass plating after anterior reconstruction provided more stability compared with unicortical or bicortical anterior plate fixation after a simulated corpectomy. SUMMARY OF BACKGROUND DATA: Previous implant biomechanical evaluations use ligamentous and intervertebral disc disruption models under constrained and nonrepetitive loading. This study examines implant performance using a corpectomy model loaded for multiple cycles, allowing for unconstrained motion. METHODS: Twenty-one porcine cervical spines were destabilized with a one-level cervical corpectomy and reconstructed with an anterior methacrylate graft. Each construct was stabilized with either an AO Morscher plate system with unicortical, self-locking screws; a Caspar plate with biocortical screws; or two posterior lateral mass plates. Testing with cyclic loads was performed on an MTS machine in flexion, extension, and axial rotation. RESULTS: There was no statistical difference between the two anterior forms of fixation in flexion, extension, or axial rotation. Posterior lateral mass plating was significantly more stable than either anterior construct. Screw loosening was seen more frequently with bicortical Caspar plating. CONCLUSIONS: After a single-level cervical corpectomy and idealized grafting, all three surgical constructs provided stability equal to or greater than the intact condition in flexion, extension, and axial rotation. In unstable cervical spine injury patterns involving anterior disruption, this study supports the use of anterior grafting combined with posterior lateral mass plating to achieve maximum stability.

Animals↗