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Normality of oligonucleotide microarray data and implications for parametric statistical analyses.

MOTIVATION: Experimental limitations have resulted in the popularity of parametric statistical tests as a method for identifying differentially regulated genes in microarray data sets. However, these tests assume that the data follow a normal distribution. To date, the assumption that replicate expression values for any gene are normally distributed, has not been critically addressed for Affymetrix GeneChip data. RESULTS: The normality of the expression values calculated using four different commercial and academic software packages was investigated using a data set consisting of the same target RNA applied to 59 human Affymetrix U95A GeneChips using a combination of statistical tests and visualization techniques. For the majority of probe sets obtained from each analysis suite, the expression data showed a good correlation with normality. The exception was a large number of low-expressed genes in the data set produced using Affymetrix Microarray Suite 5.0, which showed a striking non-normal distribution. In summary, our data provide strong support for the application of parametric tests to GeneChip data sets without the need for data transformation.

Algorithms↗

Comparative analysis of algorithms for signal quantitation from oligonucleotide microarrays.

MOTIVATION: Recent years' exponential increase in DNA microarrays experiments has motivated the development of many signal quantitation (SQ) algorithms. These algorithms perform various transformations on the actual measurements aimed to enable researchers to compare readings of different genes quantitatively within one experiment and across separate experiments. However, it is relatively unclear whether there is a 'best' algorithm to quantitate microarray data. The ability to compare and assess such algorithms is crucial for any downstream analysis. In this work, we suggest a methodology for comparing different signal quantitation algorithms for gene expression data. Our aim is to enable researchers to compare the effect of different SQ algorithms on the specific dataset they are dealing with. We combine two kinds of tests to assess the effect of an SQ algorithm in terms of signal to noise ratio. To assess noise, we exploit redundancy within the experimental dataset to test the variability of a given SQ algorithm output. For the effect of the SQ on the signal we evaluate the overabundance of differentially expressed genes using various statistical significance tests. RESULTS: We demonstrate our analysis approach with three SQ algorithms for oligonucleotide microarrays. We compare the results of using the dChip software and the RMAExpress software to the ones obtained by using the standard Affymetrix MAS5 on a dataset containing pairs of repeated hybridizations. Our analysis suggests that dChip is more robust and stable than the MAS5 tools for about 60% of the genes while RMAExpress is able to achieve an even greater improvement in terms of signal to noise, for more than 95% of the genes.

Algorithms↗

A prospective controlled trial of computerized decision support for lipid management in primary care.

OBJECTIVES: This study aimed to assess the uptake and effect in primary care of a computerized decision support system (DSS) for the management of hyperlipidaemia. METHOD: A prospective controlled trial was conducted in 25 practices covering a population of 150,000 in the city of Birmingham. The Primed system, a specialist developed, rule based DSS for general practice, was introduced prospectively after a 3-month baseline data collection. The main outcome measures were nine months' data on prescribing of lipid lowering agents; use of laboratory tests; and referrals to secondary care for the investigation of hyperlipidaemia. RESULTS: System use was lower than expected. A shift was observed towards requests for appropriate follow-up of previously abnormal lipid results and a greater emphasis on full lipid profiles, in line with the DSS guidelines. Referrals showed a 55% decrease on those expected (NS). The prescribing evaluation revealed a large variation between practices, but no significant alteration following system use. Views of users favoured decision support as a concept, but criticised technical problems with the system. CONCLUSIONS: Greater integration of DSS software and practice based data handling systems is needed. The mode of data capture, and hence both the content and form of knowledge representation, in DSS must take greater account of the primary care consultation process if such systems are to be of use to practitioners.

Attitude to Computers↗

Towards improvement of the accuracy and completeness of medication registration with the use of an electronic medical record (EMR).

BACKGROUND: Approximately 80% of GPs use a GP information system (GIS) and an electronic medical record (EMR) in their daily practice. To reap the full benefits of an EMR for patient care, post-graduate education and research, the data input must be well structured and accurately coded. OBJECTIVES: The quality and user-friendliness of the software positively influence the completeness and reliability of the data recorded in the GIS. To assess this in actual practice, this study examined whether or not an increase occurred in the accuracy and completeness of indication-related medication registration after the GIS's software package was upgraded. METHOD: GPs recorded data for the Registration Network Groningen (RNG) concerning four medication groups: insulin, trimethoprim, the contraceptive pill and beta-blocking agents. The completeness and accuracy of the registered data were assessed both before and after the change to the new software package. The completeness is evaluated on the basis of the indications missing for the prescribed medications. To assess accuracy, a check was made to determine whether the indications corresponded to those deemed relevant for that particular medication according to National Pharmaceutical Guidelines. RESULTS: The percentage of missing indications decreased notably, especially in the chronically prescribed medication groups. For insulin, the percentage decreased from 40.5 to 3% and for the contraceptive pill from 34.5 to 1%. For trimethoprim, the percentage decreased from 10 to 1%, and for beta-blocking agents from 22 to 1.5%. Of the indications present, the percentage of relevant indications showed a slight increase, with the largest increase observed for the contraceptive pill where the percentage rose from 86 to 96%. CONCLUSIONS: The completeness of recorded indications improved considerably after the change of software. This is due mostly to the efforts of the GPs, their practice assistants and the support of the RNG organization involved in the conversion procedure. Accuracy improved slightly, especially due to the software modifications which ensured that non-existent codes could not be entered. To summarize, with increased user-friendliness of the software, combined with the training of motivated GPs, the quality of recorded data improved.

Adrenergic Antagonists↗

An adaptive, object oriented strategy for base calling in DNA sequence analysis.

An algorithm has been developed for the determination of nucleotide sequence from data produced in fluorescence-based automated DNA sequencing instruments employing the four-color strategy. This algorithm takes advantage of object oriented programming techniques for modularity and extensibility. The algorithm is adaptive in that data sets from a wide variety of instruments and sequencing conditions can be used with good results. Confidence values are provided on the base calls as an estimate of accuracy. The algorithm iteratively employs confidence determinations from several different modules, each of which examines a different feature of the data for accurate peak identification. Modules within this system can be added or removed for increased performance or for application to a different task. In comparisons with commercial software, the algorithm performed well.

Algorithms↗

Review of methods and computer codes for interpretation of bioassay data.

Internal dose determination is an essential component of individual monitoring programmes for workers or members of the public exposed to radionuclides, and methods and computer programs are required for dose assessment. A recent international European Radiation Dosimetry Group (EURADOS) intercomparison has shown unacceptably large ranges in the results assessment. An ICRP working party has been initiated to consider what guidance ICRP can give on the use of models and interpret bioassay data in terms of intake/dose. In this field, six codes for bioassay data interpretation, which implement the current ICRP publication 78 biokinetic models, have been reviewed against several criteria with different levels of importance: minor criteria such as the practical use of the code and the graphical capabilities, and major criteria such as the choice of available parameters, peculiarities of data fitting and interpretation, the choice of biokinetic models and the use of uncertainties. All these criteria were assessed using one artificial set of data and two examples extracted from the previous international EURADOS intercomparison.

Administration, Oral↗

Reproducibility and accuracy of angle measurements obtained under static conditions with the Motion Analysis video system.

The development of computerized and semi-automated motion analysis systems has made the study of human motion more widely available in research and clinical settings. Although many of these systems are currently used by physical therapists, the accuracy and reproducibility of some of these systems in estimating joint angles have not been reported. In this study, the accuracy and reproducibility of angle measurements obtained by use of the Motion Analysis video system were evaluated under static conditions using a standard goniometer. Reflective markers placed on a goniometer were recorded by two video cameras at 17 angles, from 20 to 180 degrees, in 10-degree increments. Recordings of the goniometer were made at three locations within the field of view of the cameras. The intraclass correlation coefficient for each location tested was .99. Average within-trial variability was less than 0.4 degree at all locations. A linear regression of the system-calculated angles and reference angles for all locations had slopes near unity (ie, 1) and intercepts that were not statistically different from zero. A preliminary evaluation of the system under dynamic conditions revealed that distances were slightly underestimated, regardless of where the movement occurred within the calibration cube.

Algorithms↗

Evaluating computerized health information systems: hardware, software and human ware: experiences from the Northern Province, South Africa.

Despite enormous investment world-wide in computerized health information systems their overall benefits and costs have rarely been fully assessed. A major new initiative in South Africa provides the opportunity to evaluate the introduction of information technology from a global perspective and assess its impact on public health. The Northern Province is implementing a comprehensive integrated hospital information system (HIS) in all of its 42 hospitals. These include two mental health institutions, eight regional hospitals (two acting as a tertiary complex with teaching responsibilities) and 32 district hospitals. The overall goal of the HIS is to improve the efficiency and effectiveness of health (and welfare) services through the creation and use of information, for clinical, administrative and monitoring purposes. This multi-site implementation is being undertaken as a single project at a cost of R130 million (which represents 2.5 per cent of the health and welfare budget on an annual basis). The implementation process commenced on 1 September 1998 with the introduction of the system into Mankweng Hospital as the pilot site and is to be completed in the year 2001. An evaluation programme has been designed to maximize the likelihood of success of the implementation phase (formative evaluation) as well as providing an overall assessment of its benefits and costs (summative evaluation). The evaluation was designed as a form of health technology assessment; the system will have to prove its worth (in terms of cost-effectiveness) relative to other interventions. This is more extensive than the traditional form of technical assessment of hardware and software functionality, and moves into assessing the day-to-day utility of the system, the clinical and managerial environment in which it is situated (humanware), and ultimately its effects on the quality of patient care and public health. In keeping with new South African legislation the evaluation process sought to involve as many stakeholders as possible at the same time as creating a methodologically rigorous study that lived within realistic resource limits. The design chosen for the summative assessment was a randomized controlled trial (RCT) in which 24 district hospitals will receive the HIS either early or late. This is the first attempt to carry out an RCT evaluation of a multi-site implementation of an HIS in the world. Within this design the evaluation will utilize a range of qualitative and quantitative techniques over varying time scales, each addressing specific aims of the evaluation programme. In addition, it will attempt to provide an overview of the general impact on people and organizations of introducing high-technology solutions into a relatively unprepared environment. The study should help to stimulate an evaluation culture in the health and welfare services in the Northern Province as well as building the capacity to undertake such evaluations in the future.

Computers↗

Role of contact and noncontact mapping in the curative ablation of tachyarrhythmias.

Assessment of the timing of electrical activation recorded by multiple electrodes positioned in various locations within the heart has been the conventional method for mapping cardiac arrhythmias. This technique requires fluoroscopy for catheter manipulation, which in addition to being harmful (ionizing radiation), is inadequate for visualizing the complex three-dimensional cardiac anatomy and lacks reproducibility regarding localization of sites of interest. Because of these limitations, several new mapping systems that can function in a complimentary role to the conventional mapping technique, or can be used independently, have been developed. These new mapping strategies have unique advantages. They overcome the limitations of fluoroscopy by creating accurate three-dimensional intracardiac maps. The ability to localize and accurately display intracardiac catheter positioning and ablation lesion sites facilitate increasingly complex catheter ablation procedures.

Body Surface Potential Mapping↗

Influence of a computer database and problem exercises on students' knowledge of bacteriology.

This study compared the performances of students at the University of North Carolina at Chapel Hill School of Medicine who had access to sets of problem exercises and a computer database to support their learning of bacteriology with the performances of students at the University of Iowa College of Medicine who did not have such access. The study also examined the extent of a student's database use as a predictor of posttest performance. The students studied were randomly selected groups of 32-44 first-year students per year at each school; the study was conducted in three academic years (1988-1990) with some modifications in the intervention as the host environment evolved. The criterion measure was a posttest created from the same pool of problems used to generate the problem sets. The students at the intervention school scored significantly higher on the posttest in two of the three years, and overall. Also in two of the three years and overall, there was a significant relationship between the extent of a student's database use and his or her posttest score. Although the observed effects may have been due to other factors in this quasi-experimental design, the authors conclude that the use of problem sets and a computer database had a positive influence on the students' learning.

Bacteriology↗

A reexamination of the NRMP matching algorithm. National Resident Matching Program.

Most graduating medical students in the United States find their first professional appointments through the National Resident Matching Program (NRMP). This service receives rank-order lists of preferences from students and from hospitals, and then generates final assignments of students to hospitals through the use of a specific computerized matching algorithm. The author uses recent findings from the mathematics and economics literatures to demonstrate three difficulties with the NRMP's matching algorithm and the official descriptions thereof. First, the algorithm favors hospitals over students, a feature known to the NRMP since at least 1976, but, in the author's opinion, not made clear in NRMP literature for students. Second, the author argues that the NRMP's justification that its algorithm mimics orderly, noncentralized admission processes is not correct. Institutions operating under non-centralized procedures must typically make more initial offers than there are positions, in the realization that some fraction of their offers will be declined. This arrangement enlarges the choices available to many applicants, and thereby benefits them, whereas the NRMP's algorithm unrealistically assumes that no institution would ever send out any extra offers. Third, the NRMP's algorithm contains incentives for students to misrepresent their true preferences when constructing their rank-order lists. This feature is a substantial disadvantage of the current algorithm and is incorrectly described in literature distributed to students and in published articles from the NRMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗

The NRMP matching algorithm revisited: theory versus practice. National Resident Matching Program.

The authors examine the algorithm used by the National Resident Matching Program (NRMP) in its centralized matching of applicants to U.S. residency programs ("the Match"). Their goal is to evaluate the current NRMP matching algorithm to determine whether it still fulfills its intended purpose adequately and whether changes could be made that would improve the Match. They describe the basic NRMP algorithm and many of the variations of the matching process ("match variations") incorporated over the last 20 years to meet participants' requirements. An overview of the current state of the theory of preference matching is presented, including descriptions of the characteristics of stable matches in general, program-optimal and applicant-optimal matchings, and strategies for formulating preference lists. The characteristics of the current NRMP algorithm are then compared with the theoretical findings. Research conducted long after the original NRMP algorithm was devised has shown that an algorithm that produces stable matches is the best approach for matching applicants to positions. In the absence of requirements to satisfy match variations, the NRMP's deferred-acceptance algorithm produces a program-optimal stable match. When match variations, such as those handled by the NRMP, must be introduced, it is possible that no stable matching exists, and the resulting matching produced by the NRMP algorithm may not be program-optimal. The question of program-optimal versus applicant-optimal matchings is discussed. Theoretical and empirical evidence currently available suggest that differences between these two kinds of matchings are likely to be small. However, further tests and research are needed to assess the real differences in the results produced by different stable matching algorithms that produce program-optimal or applicant-optimal stable matches.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗

Outcomes management of mechanically ventilated patients: utilizing informatics technology.

This article examines an informatics system developed for outcomes management of the mechanically ventilated adult population, focusing on weaning the patient from mechanical ventilation. The link between medical informatics and outcomes management is discussed, along with the development of methods, tools, and data sets for outcomes management of the mechanically ventilated adult population at an acute care academic institution. Pros and cons of this system are identified, and specific areas for improvement of future health care outcomes medical informatics systems are discussed.

Adult↗

Tritium dose overestimates by CAP88-PC.

The dose assessment software CAP88-PC may overestimate doses from tritium under some conditions. The overestimates are linked to three key assumptions implicit in the software that may not be immediately parent. The three assumptions are (1) the contribution of home grown food, (2) the distances at which food is produced, and (3) the number of people consuming locally produced food.

Agriculture↗

Meeting the educational needs of clinical equipment users.

Training equipment users to operate medical equipment effectively and safely is one of the most important and difficult tasks of clinical engineers. As medical equipment proliferates and becomes more complex, the task of education also becomes more difficult. The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) requires that all equipment users be trained annually in proper operating procedures for the equipment they use and that the training be documented. Therefore, each hospital must develop educational programs to meet those needs. This paper illustrates the use of an interactive computer-assisted instruction (CAI) program, entitled EquipTeach, to provide an effective, standardized and cost-effective method of training equipment users at the John Dempsey Hospital of The University of Connecticut Health Center in Farmington, Connecticut.

Computer-Assisted Instruction↗

Minding the store: how IT impacts outcomes measurement.

Today, the question is not whether organizations should measure outcomes, but how. Right now, there are several initiatives, but no single, collaborative effort to tie them all together. This article will discuss the rise and early history of outcomes assessment in health care and highlight some key current initiatives (for example, OASIS [home health], QISMC [managed care organizations], HCQIP [inpatient care], ACQIP [ambulatory care], Joint Commission's ORYX accreditation initiative [hospitals, long-term care, home care, behavioral health care, and networks]). It will also delineate some of the problems with measuring outcomes and discuss where more work is needed. It will go on to discuss the role of IT in outcomes measurement, including its contributions, goals, effects, categories of IT support, infrastructure solutions, and analysis.

Data Interpretation, Statistical↗

Assisting students at risk: using computer NCLEX-RN review software.

In response to a decline in the success rate on the National Council Licensure Examination for Registered Nurses (NCLEX-RN) examination, the authors developed a program to identify and assist students at risk for failure. The use of a computerized NCLEX-RN practice examination and an individualized student review and study process is described.

Computer-Assisted Instruction↗