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PubMed1984

A comparison of methods to approximate standard errors for complex survey data.

Complex survey designs are characterized by multistage selections with stratification and clustering. The departure from simple random sampling assumptions requires special consideration with regard to variance estimation. Specially designed software packages exist to generate variance estimates for statistics from complex survey data. The variance estimation techniques used include balanced repeated replication, jackknife, and Taylor series linearization. Many complex surveys generate thousands of tables. The computational and publishing costs soar if estimates of standard error are required for all statistics. To decrease these costs, several alternative techniques to approximate the standard errors of estimates are available. These include the widely used relative variance curve, a method based on the average relative standard error, and the average design effect model. In this paper these three methods are compared with respect to accuracy, computational and publishing costs, and ease of implementation.

Health Services Research↗

PubMed2005

Computing TaqMan probes for multiplex PCR detection of E. coli O157 serotypes in water.

Diarrheagenic E. coli strains contribute to water related diseases in urban and rural environment in developing and developed world. E. coli pathotype and pathogenicity varies due to complex multifactorial mechanism involving a large number of virulence factors. Rapid assessment of the virulence pattern of E. coli isolates is possible by Real-Time PCR probes like TaqMan. For designing TaqMan probes and primers for multiplex PCR selected E. coli gene sequences: stx1, stx2, hlyA, chuA, eae, lacZ, lamB and fimA were retrieved from NCBI's GenBank database. The alignment of the multiple sequences and analysis of conserved sequences was carried out using ClustalW and BLAST programs. The primers and Taqmen probes were designed using Beacon Designer software version 2.1 for two multiplexed PCR assays. In silico PCR simulation of these assays showed PCR products for stx2 (248bp) stx1 (102 bp), lacZ (228bp) and lamB (86 bp) in multiplex #1 and eae (200bp), chuA (147 bp), hlyA (141bp) and fimA (79 bp) in multiplex #2, respectively. These multiplexed PCR amplification products and probes can be used to identify and confirm presence of O157:H7/ H7-, O157:H43/45 and O26:H-/H11 serotypes. In conclusion, multiplex Real-Time Polymerase Chain Reaction oligomers and TaqMan probes designed and validated in silico will be helpful in management of water quality and outbreaks, by improving specificity and minimizing time needed for in vitro verification work.

Base Sequence↗

PubMed2005

AKA-Glucose: a program for kinetic and epidemiological analysis of frequently sampled intravenous glucose tolerance test data using database technology.

BACKGROUND: The Bergman Minimal Model enables estimation of two key indices of glucose/ insulin dynamics: glucose effectiveness and insulin sensitivity. METHODS AND RESULTS: In this paper we describe AKA-Glucose, a program that combines MINMOD Millennium (minimal model analysis software) with relational database technologies. AKA-Glucose enables the fitting of individual frequently sampled intravenous glucose tolerance test (FSIGT) data sets to the Minimal Model and the secure storage in a dedicated database (and retrieval from) of thousands of individual subjects' demographic data, their individual FSIGT data, and each subject's parameters and indices derived from minimal model analysis. AKA-Glucose also enables the population analysis of various strata or subpopulations within the database. AKA-Glucose has all of the capabilities of MINMOD Millennium, provides Minimal Model parameter estimates that are concordant with estimates from previous MINMOD software, and allows importation of data files from earlier versions of the MINMOD software. CONCLUSIONS: By combining FSIGT data fitting, population analysis, and relational database technologies, AKA-Glucose is the first minimal model software designed specifically for researchers confronted with minimal model and epidemiological analysis of large numbers of either human or animal FSIGT data sets.

Adult↗

PubMed2005

MSight: an image analysis software for liquid chromatography-mass spectrometry.

Images obtained from high-throughput mass spectrometry (MS) contain information that remains hidden when looking at a single spectrum at a time. Image processing of liquid chromatography-MS datasets can be extremely useful for quality control, experimental monitoring and knowledge extraction. The importance of imaging in differential analysis of proteomic experiments has already been established through two-dimensional gels and can now be foreseen with MS images. We present MSight, a new software designed to construct and manipulate MS images, as well as to facilitate their analysis and comparison.

Chromatography, Liquid↗

PubMed1977

Computer-assisted monocyte esterase assay by flow-cytophotometry.

A Wang model 2200 computer has been interfaced with the Bio/Physics Systems, Inc. model 6300 Cytograf and model 2100 Distribution Analyzer. Using a custom designed software program, in conjunction with an azo-dye technic for staining monocytes for nonspecific esterase activity, it has been possible to obtain rapid and reliable data concerning relative values for intracellular monocyte esterase activity. The method is based on measuring the axial light-loss voltage signal for each of one thousand stained monocytes. Individual stained monocytes were assigned to one of four groups (A, B, C, D), dependent upon the magnitude of the signal and were given different rating values (1, 2, 3, 4) according to their group designation. A "score" was derived for each blood sample by multiplying the percentage of cells (monocytes) in each group category by the appropriate factor and summing these values. The technic permits rapid objective assessment of intracellular nonspecific esterase activity in monocytes suspended in a mixed cell population. Both Gaussian and bi-modal patterns for monocyte esterase were observed. The latter suggests a dual monocyte population.

Computers↗

PubMed2004

Assessing convergence of Markov chain Monte Carlo simulations in hierarchical Bayesian models for population pharmacokinetics.

Advances in computer hardware and the associated computer-intensive algorithms made feasible by these advances [like Markov chain Monte Carlo (MCMC) data analysis techniques] have made possible the application of hierarchical full Bayesian methods in analyzing pharmacokinetic and pharmacodynamic (PK-PD) data sets that are multivariate in nature. Pharmacokinetic data analysis in particular has been one area that has seized upon this technology to refine estimates of drug parameters from sparse data gathered in a large, highly variable population of patients. A drawback in this type of analysis is that it is difficult to quantitatively assess convergence of the Markov chains to a target distribution, and thus, it is sometimes difficult to assess the reliability of estimates gained from this procedure. Another complicating factor is that, although the application of MCMC methods to population PK-PD problems has been facilitated by new software designed for the PK-PD domain (specifically PKBUGS), experts in PK-PD may not have the necessary experience with MCMC methods to detect and understand problems with model convergence. The objective of this work is to provide an example of a set of diagnostics useful to investigators, by analyzing in detail three convergence criteria (namely the Raftery and Lewis, Geweke, and Heidelberger and Welch methods) on a simulated problem and with a rule of thumb of 10,000 chain elements in the Markov chain. We used two publicly available software packages to assess convergence of MCMC parameter estimates; the first performs Bayesian parameter estimation (PKBUGS/WinBUGS), and the second is focused on posterior analysis of estimates (BOA). The main message that seems to emerge is that accurately estimating confidence regions for the parameters of interest is more demanding than estimating the parameter means. Together, these tools provide numerical means by which an investigator can establish confidence in convergence and thus in the estimated parameters derived from hierarchical full Bayesian pharmacokinetic data analysis.

Algorithms↗

PubMed2002

High performance bilateral telerobot control.

Telerobotic systems are used when the environment that requires manipulation is not easily accessible to humans, as in space, remote, hazardous, or microscopic applications or to extend the capabilities of an operator by scaling motions and forces. The Creare control algorithm and software is an enabling technology that makes possible guaranteed stability and high performance for force-feedback telerobots. We have developed the necessary theory, structure, and software design required to implement high performance telerobot systems with time delay. This includes controllers for the master and slave manipulators, the manipulator servo levels, the communication link, and impedance shaping modules. We verified the performance using both bench top hardware as well as a commercial microsurgery system.

Algorithms↗

PubMed1988

The protein identification resource (PIR).

The Protein Identification Resource consists of an integrated computer system composed of a number of protein and nucleic acid sequence databases and software designed for the identification and analysis of protein sequences and their corresponding coding sequences. The PIR serves the scientific community through on-line access, distributing magnetic tapes, and performing off-line sequence identification services for researchers.

Amino Acid Sequence↗

PubMed2000

The reliability and internal consistency of an Internet-capable computer program for measuring utilities.

OBJECTIVE: The purpose of this study was to assess the reliability and internal consistency of measurements of utilities performed with a computer program (iMPACT2) designed for Internet surveys and Internet patient decision-support systems. METHODS: We implemented the Internet Multimedia Preference Assessor Construction Tool, version 2 (iMPACT2) program using the combination of a web server, HTML files, and a web-accessible database. The program randomized subjects, screened their responses for missing data and failures of internal consistency, assisted patients with resolving certain inconsistencies, and, upon a subject's completion of the protocol, provided a report of results to the research assistant administering the program. To validate the iMPACT2 program, we recruited 60 healthy community volunteers and elicited preferences in a research-lab setting using a visual analog scale (VAS) and the standard gamble (SG) for subject's current health and three hypothetical states. For purposes of comparison, we also administered a Short Form-12 (SF-12) health-assessment questionnaire. Subjects used the computer software on two occasions separated by 2-4 weeks of time. RESULTS: Visual analog scale and standard gamble ratings for subjects' current health were reliable (intraclass correlation coefficient (ICC) of 0.82 and 0.84 (two outliers excluded -0.60 without exclusions), respectively) were comparable with the reliability of the Physical and Mental Component scales of the SF-12 (ICCs of 0.84 and 0.75, respectively). Subjects could easily discriminate between hypothetical states (D scores 0.74 for SG and 0.90 for VAS), and 94% had a completely internally consistent ordering of preference ratings for states. CONCLUSIONS: iMPACT2 produces measurements of standard gamble utilities that are reliable and have a high degree of internal consistency. Procedures for assessment of utilities developed for desktop computer programs can be translated to software designed for the Internet, facilitating the use of utilities and endpoints in clinical trials and development of web-based decision-support applications for patients. However, further testing, including direct comparisons with traditional interviewer administered utility elicitation protocols, is needed.

Analysis of Variance↗

PubMed2002

Electronic procedure logs: taking it further.

OBJECTIVE: To create an electronic procedural logbook with enhanced user interactivity and usefulness as an educational resource. DESCRIPTION: From our own work on electronic student logbooks and other studies, it is clear that compliance with complete and valid data entry remains a challenge. Without direct and visible benefit, students are reluctant to spend time logging all their cases. We developed an interactive procedural logbook using Microsoft Embedded Visual Basic and Metrowerks CodeWarrior. Interface design focused on rapid data entry with minimum requirement for text, and field-level automation where possible. We loaded it onto a mixed platform of personal digital assistants (PDAs)--Compaq iPaq Pocket PCs and HandEra 330 PalmOS devices. Our rural residents were supplied with the devices of their choice. Various built-in educational reference resources included: (1) contextual help options about each procedure, which contained diagrams and pictures; (2) diagnostic and fee coding so they could see how poorly some procedures pay; and (3) Quick Tips relevant to each procedure, which can be easily modified by the preceptor. Preceptor evaluations and comments can be entered rapidly. Using built-in database conduits, data are automatically collected from each device on every HotSync with the desktop. Data can then be collated and analyzed using Microsoft Access or via secure Web access. DISCUSSION: Improved compliance has been dramatic-one resident logged 250 procedures in just two months. However, not all residents have been successful in establishing seamless synchronization, and the resulting data loss has caused frustration. The evidence indicates the need to implement central data collection and backup right from the outset. Central data collection provides many advantages. The program director has better information for future applications. Preceptor evaluations are now spread over many interactions and yet can be collated and analyzed. Quick Tips have been very popular-we have been able to collect the tips and redistribute them. Focus-group feedback from the residents has shown that the rich data in the logbook's reference component improved its usefulness and popularity as an educational tool. Choice of device type is important for user acceptance because devotees of one platform are reluctant to switch to another. Cross-platform development does slow the process but is increasingly easy with the latest software design tools, such as AppForge. These new tools have enabled us to explore further improvements in data entry. Digital ink provides the ability to capture annotated diagrams and preceptor signatures. Voice input is built in with these devices, and our software now allows for voice annotation for more detailed commentary by preceptors or student. The compressed digital sound file is collected along with the data and transcribed centrally (on-device voice recognition is not feasible yet). Point-of-care accessibility has been the key attraction of using these devices for logging encounter data. This project demonstrates that it is important to explore all multimodal interactive capabilities to provide a truly rich educational tool.

Electronic Data Processing↗

PubMed1996

Strategies to promote rational clinical chemistry test utilization.

OBJECTIVE: To critically review the elements of laboratory services that result in inappropriate ordering of clinical chemistry tests and the efficacy of corrective interventions. METHODS AND RESULTS: In our experience, inappropriate use of laboratory services derives from multiple factors, including the use of multitest profiles, organ- or disease-specific test panels, indiscriminate ordering, standing orders, excessive reporting delays, poor audit trails of test requests, rigid group test ordering, failure to eliminate obsolete tests, and some features of computer software design. Educational strategies can be effective in modifying test-ordering patterns, provided there is sustained feedback to physicians. Careful design of requisitions and the use of disease-specific algorithms have also proven effective. CONCLUSION: Limited resources must be directed to where they are most effective by optimizing laboratory work-flow from test ordering to reporting, to avoid practices that promote inappropriate laboratory use.

Chemistry, Clinical↗

PubMed1995

Prefabricated prostheses for the reconstruction of skull defects.

Cranioplasties using intraoperatively modeled prostheses may fail to create harmonic contours with long-term stability. In contrast, preoperative modeling would allow more sophisticated planning of the contour and better preparation of the implant material, if a sufficiently precise model of the defect-site was available. In this respect, computer aided design and manufacturing (CAD/CAM)-techniques based on helical computed tomography (CT) data are successfully used for the prefabrication of prostheses: An individual computer-based 3-dimensional model of the bony defect is generated after acquisition, transfer and evaluation of the CT data; from this freeform surfaces geometry an individual and "idealized" prosthesis-geometry is derived and fabricated by a numerically controlled milling machine using modern industrial CAD/CAM-systems and design software. The margins of this prosthesis-geometry are generated by the borders of the defect and the surface by considering the non-affected neighbouring contours. Cranioplasties in cases of large postsurgical skull defects are presented as the first clinical applications of this new method, which also allows the use of titanium and fabrication of integrated fixation-devices.

Computer Simulation↗

PubMed2005

A simple and practical method to acquire geometrically correct images with resonant scanning-based line scanning in a custom-built video-rate laser scanning microscope.

Most currently available confocal or two-photon laser scanning microscopes (LSMs) allow acquisition rates of the order of 1-5 images s(-1), which is too slow to fully resolve dynamic changes in intracellular messenger concentration in living cells or tissues. Several technologies exist to obtain faster imaging rates, either in the video-rate range (30 images s(-1)) or beyond, but the most versatile technology available today is based on resonant scanners for horizontal line scanning. These scanning devices have several advantages over designs based on acousto-optical deflectors or Nipkow discs, but a drawback is that the scanning pattern is not a linear but rather a sinusoidal function of time. This puts additional constraints on the hardware necessary to read-in the image data flow, one of which is the generation of a pixel clock that varies in frequency with the position of the pixel on the scanned line. We describe a practical solution to obtain a variable pixel clock add-on that is easy to build and is easy to integrate into a custom-built LSM based on resonant scanning technology. In addition, we discuss some important hardware and software design aspects that simplify the construction of a resonant scanning-based LSM for high-speed, high-resolution imaging. Finally, we demonstrate that the microscope can be used to resolve calcium puffs triggered by photolytically increasing the intracellular concentration of inositol trisphosphate.

Journal Article↗

PubMed1996

Dynamics of QT dispersion during myocardial infarction and ischaemia.

We studied the dynamics of QT dispersion over the first few days of myocardial infarction and during coronary angioplasty. Ten patients with anterior myocardial infarction and an equal number with inferior infarction had electrocardiograms (ECGs) recorded on admission to hospital (day 1), on the subsequent 2 days (day 2, 3), and prior to discharge (day 6). Ten patients undergoing therapeutic coronary angioplasty were studied; ECGs were recorded prior to, during, and after balloon inflation. Simultaneous 12-lead ECGs were scanned into a personal computer; specially designed software skeletonised and joined each image. The images were then available for user-interactive measurement of QT dispersion. Mean (S.D.) QTc dispersion on day 1 of acute myocardial infarction was 107 (44.8) ms, rose further over the next 48 h, reaching a maximum on day 3 (QTc dispersion, 162.3 (64.8) ms, P < 0.01), and was falling by hospital discharge (QTc dispersion, 117.4 (67.4) ms). There was no difference in QT dispersion measurement during coronary angioplasty. It is unlikely that acute ischaemia plays an important role in the dynamic changes seen in QT dispersion over the first few days of myocardial infarction. These rapid changes in QT dispersion have important implications in the design of any study of QT dispersion after myocardial infarction, and in comparison of studies.

Angioplasty, Balloon, Coronary↗

PubMed1999

Estimated intakes of trans fatty and other fatty acids in the US population.

OBJECTIVE: To estimate mean level of trans fatty acid intakes using a representative sample of the US population. DESIGN: The study used food intake data from the 1989-1991 Continuing Survey of Food Intakes by Individuals (CSFII) and the trans fatty acid contents of specific foods calculated from a database compiled by the US Department of Agriculture (USDA) to estimate the mean level and deciles of trans fatty acid intake of the representative US population. SUBJECTS/SETTING: Trans fatty acid intakes were estimated for each subject (N = 11,258) in the CSFII data who completed both a 24-hour recall and a 2-day food record. STATISTICAL ANALYSES PERFORMED: Weights developed by USDA for the survey were used for all data analyses. The Technical Assessment Systems (TAS) International Diet Research System (TAS-DIET), software developed by TAS, was used to derive weighted estimates of the mean and percentiles of the intake distribution. PC CARP, software designed by Iowa State University, was used to estimate standard errors. RESULTS: Mean percentage of energy ingested as trans fatty acids was 2.6% and the mean percentage of total fat ingested as trans fatty acids was 7.4%. Across all age and gender groups examined, estimates ranged from 2.6% to 2.8% and 7.1% to 7.9%, respectively. APPLICATIONS/CONCLUSIONS: Dietetics practitioners can use the representative data of this study to help clients achieve desired changes in consumption levels of trans fatty acids.

Adolescent↗

PubMed2001

Learning to consult with computers.

OBJECTIVE: To develop and evaluate a strategy to teach skills and issues associated with computers in the consultation. INTERVENTION: An overview lecture plus a workshop before and a workshop after practice placements, during the 10-week general practice (GP) term in the 5th year of the University of Melbourne medical course. DESIGN: Pre- and post-intervention study using a mix of qualitative and quantitative methods within a strategic evaluation framework. OUTCOME MEASURES: Self-reported attitudes and skills with clinical applications before, during and after the intervention. RESULTS: Most students had significant general computer experience but little in the medical area. They found the workshops relevant, interesting and easy to follow. The role-play approach facilitated students' learning of relevant communication and consulting skills and an appreciation of issues associated with using the information technology tools in simulated clinical situations to augment and complement their consulting skills. The workshops and exposure to GP systems were associated with an increase in the use of clinical software, more realistic expectations of existing clinical and medical record software and an understanding of the barriers to the use of computers in the consultation. CONCLUSIONS: The educational intervention assisted students to develop and express an understanding of the importance of consulting and communication skills in teaching and learning about medical informatics tools, hardware and software design, workplace issues and the impact of clinical computer systems on the consultation and patient care.

Attitude to Computers↗

PubMed2002

Minimally invasive spectroscopic system for intraocular drug detection.

A novel, minimally invasive measurement technique has been developed for the detection of drugs in the anterior chamber of the eye. Presently there is no satisfactory, real-time detection method available to the ophthalmic community. Accurate determination of drug concentrations in the eye would be of great value and assistance to researchers and manufacturers of ophthalmic drugs and ocular implants, to enable a better understanding of intraocular pharmacokinetics. At present researchers use techniques of direct sampling of the aqueous humor from laboratory animal eyes into which the drug has been introduced topically or systemically. Rabbit eyes are frequently used in this context. Sampling via paracentesis is invasive, and does not yield a continuous measurement. Our approach to addressing this measurement requirement is, in effect, to turn the eye into a cuvette and use optical absorbance spectroscopy measurements to detect drug concentrations. A novel contact lens has been designed using commercial, off-the-shelf, optical design software. The lenses have been optimized to direct light across the anterior chamber of a rabbit's eye. Practical demonstration and characterization of light propagation across the eye have been undertaken and are reported. Preliminary results of the identification of drug compounds introduced into model eyes are also reported.

Adrenergic alpha-Agonists↗

PubMed2000

Essential motions and energetic contributions of individual residues in a peptide bound to an SH3 domain.

We have studied protein-ligand interactions by molecular dynamics simulations using software designed to exploit parallel computing architectures. The trajectories were analyzed to extract the essential motions and to estimate the individual contributions of fragments of the ligand to overall binding enthalpy. Two forms of the bound ligand are compared, one with the termini blocked by covalent derivatization, and one in the underivatized, zwitterionic form. The ends of the peptide tend to bind more loosely in the capped form. We can observe significant motions in the bound ligand and distinguish between motions of the peptide backbone and of the side chains. This could be useful in designing ligands, which fit optimally to the binding protein. We show that it is possible to determine the different contributions of each residue in a peptide to the enthalpy of binding. Proline is a major net contributor to binding enthalpy, in keeping with the known propensity for this family of proteins to bind proline-rich peptides.

Amino Acid Sequence↗