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At least 163 records · Page 9Linked to original sources

Evaluation of Sleep Expert--a computer-aided decision support system for sleep disorders.

Sleep Expert--a medical decision support system--is a prototype program, with knowledge based on the International Classification of Sleep Disorders (1990). The goal of this project was to evaluate Sleep Expert. In the evaluation project the knowledge of the program was first validated. Three physicians, experts in sleep disorders, were asked to choose 10 typical patient cases with sleep disorders, and to write a description. They also made a diagnosis for each case. Next, each expert made a diagnosis of the cases supplied by the other experts. They were not given the original diagnosis. The 'right diagnosis' (so-called majority agreement) was determined from the three diagnoses. Then the diagnosis of each expert was compared with the 'right diagnosis'. Two physicians, not experts in sleep disorders, were asked to make a diagnosis by using Sleep Expert. Compared to the 'right diagnosis' the diagnoses of each user (non-expert physician) were correct to 63 and 70% of cases, which is quite a good result, although it does not reach the level of the expert physicians (> or = 87%). The functionality of Sleep Expert was studied by using a limited inquiry. On the basis of the user inquiry Sleep Expert provided a useful clinical tool for non-experts.

Diagnosis, Computer-Assisted↗

Risk-adjusting acute myocardial infarction mortality: are APR-DRGs the right tool?

OBJECTIVE: To determine if a widely used proprietary risk-adjustment system, APR-DRGs, misadjusts for severity of illness and misclassifies provider performance. DATA SOURCES: (1) Discharge abstracts for 116,174 noninstitutionalized adults with acute myocardial infarction (AMI) admitted to nonfederal California hospitals in 1991-1993; (2) inpatient medical records for a stratified probability sample of 974 patients with AMIs admitted to 30 California hospitals between July 31, 1990 and May 31, 1991. STUDY DESIGN: Using the 1991-1993 data set, we evaluated the predictive performance of APR-DRGs Version 12. Using the 1990/1991 validation sample, we assessed the effect of assigning APR-DRGs based on different sources of ICD-9-CM data. DATA COLLECTION/EXTRACTION METHODS: Trained, blinded coders reabstracted all ICD-9-CM diagnoses and procedures, and established the timing of each diagnosis. APR-DRG Risk of Mortality and Severity of Illness classes were assigned based on (1) all hospital-reported diagnoses, (2) all reabstracted diagnoses, and (3) reabstracted diagnoses present at admission. The outcome variables were 30-day mortality in the 1991-1993 data set and 30-day inpatient mortality in the 1990/1991 validation sample. PRINCIPAL FINDINGS: The APR-DRG Risk of Mortality class was a strong predictor of death (c = .831-.847), but was further enhanced by adding age and sex. Reabstracting diagnoses improved the apparent performance of APR-DRGs (c = .93 versus c = .87), while using only the diagnoses present at admission decreased apparent performance (c = .74). Reabstracting diagnoses had less effect on hospitals' expected mortality rates (r = .83-.85) than using diagnoses present at admission instead of all reabstracted diagnoses (r = .72-.77). There was fair agreement in classifying hospital performance based on these three sets of diagnostic data (K = 0.35-0.38). CONCLUSIONS: The APR-DRG Risk of Mortality system is a powerful risk-adjustment tool, largely because it includes all relevant diagnoses, regardless of timing. Although some late diagnoses may not be preventable, APR-DRGs appear suitable only if one assumes that none is preventable.

Adult↗

Linear models for the prediction of stature from foot and boot dimensions.

Estimation of stature from the dimensions of foot or shoeprints has considerable forensic value in developing descriptions of suspects from evidence at the crime scene and in corroborating height estimates from witnesses. This study extends the findings of previous researchers by exploring linear models with and without gender and race indicators, and by validating the most promising models on a large, recently collected military database. Boot size and outsole dimensions are also examined as predictors of stature. The results of this study indicate that models containing both foot length and foot breadth are significantly better than those containing only foot length. Models with race/gender indicators also perform significantly better than do models without race/gender indicators. However, the difference in performance is slight, and the availability of reliable gender and race information in most forensic situations is uncertain. Analogous results were obtained for models utilizing boot size/width and outsole length/width, and in this study these variables performed nearly as well as the foot dimensions themselves. Although the adjusted R2 values for these models clearly reflect a strong relationship between foot/boot length and stature, individual 95% prediction limits for even the best models are +/- 86 mm (3.4 in.). This suggests that models estimating stature from foot/shoe-prints may be useful in the development of subject descriptions early in a case but, because of their imprecision, may not always be helpful in excluding individual suspects from consideration.

Anthropometry↗

Validating a decision support system for anti-epileptic drug treatment. Part I: initiating anti-epileptic drug treatment.

In this contribution the validation of a prototype decision support system that implements a model of expertise for initiating anti-epileptic drug treatment is described. Since domain experts were of the opinion that prescribing was a rather straightforward process we used only one expert neurologist for knowledge elicitation. To determine the correctness of the system we intended to compare the contents of the system's prescriptions with the majority decision of three neurologists. Because of a large variation in prescribing a majority decision could not be obtained in many cases. Even a Delphi procedure did not yield a majority decision in a large number of cases. Therefore a consensus meeting was organised to discuss cases where discrepancies remained. In the process the participating neurologists formulated prescription guidelines. These guidelines were used as a reference to determine the correctness of the prescriptions of both the system and of the neurologists. The acceptability of all prescriptions for each case was rated by the two neurologists who did not write a prescription for that case. From both comparisons it could be concluded that the system was at least as good in prescribing as individual neurologists.

Adolescent↗

The Australian Incident Monitoring Study. Crisis management--validation of an algorithm by analysis of 2000 incident reports.

Anaesthetists are called upon to manage complex life-threatening crises at a moment's notice. As there is evidence that this may require cognitive tasking beyond the information-processing capacity of the human brain, it was decided to try and develop a generic crisis management algorithm analogous to the "Phase I" immediate response routine used by airline pilots. Such an algorithm, based on the mnemonic "COVER ABCD, A SWIFT CHECK", was developed and refined over 3 meetings, each attended by 60-100 anaesthetists and aviation psychologists. It was validated against 1301 relevant incidents among the first 2000 incidents reported to the Australian Incident Monitoring Study. It proved sufficiently robust and safe to recommend its general use as an initial response to any incident or crisis which occurs when a patient is breathing gas from an anesthetic machine. It requires a limited knowledge base and is easily learnt and rehearsed during the anaesthetist's working day. It will provide a functional diagnosis in over 99% of cases and will correct 62% of the problems in 40-60 seconds. In the remaining 37% it will allow the anaesthetist to proceed with a "sub-algorithm", confident in the knowledge that some important step has not been missed. In just over 30% of incidents this will be for a problem familiar to all anaesthetists (e.g. laryngospasm, bradycardia); in just over 6% it will be for a less common, more complex, but finite, set of problems (3% cardiac arrest, 1% air embolism, 1% anaphylaxis, 1% for the remaining desaturations); in less than 1% diagnosis and correction will require a more complex checklist (e.g. for malignant hyperthermia, pneumothorax). The next stage, the development of specific sub-algorithms and a structured team approach for ongoing problems, is in progress.

Algorithms↗

Validation of PD Adequest 2.0 for pediatric dialysis patients.

Kinetic modeling has proven to be a valuable tool for peritoneal dialysis (PD) prescription in adult PD patients. The clinical application of this procedure has rarely been studied in children. We therefore evaluated the PD Adequest 2.0 for Windows program (Baxter Healthcare Co., Deerfield, IL) as a prescription aid for the management of pediatric PD patients by comparing the measured and predicted PD clearances, total drain volumes, and net ultrafiltration in 34 children (15 males) (mean age 10.9 +/- 6.0 years) receiving long-term PD. In each case, a 4-h peritoneal equilibration test was conducted with a standardized test exchange volume of 1,100 ml/m2 BSA. A total of 43 24-h dialysate (plus urine in 12) collections were analyzed. The levels of agreement between measured and predicted values for weekly peritoneal and total urea Kt/V, weekly peritoneal and total creatinine clearance, daily drain volume, net ultrafiltration and daily peritoneal urea and creatinine mass removal were assessed with correlation coefficients (re) and Bland-Altman limits of agreement. The study revealed that there is a basic level of agreement between measured and modeled values for solute removal and total drain volume, with correlation coefficients ranging from 0.75 to 0.98. In contrast, the rc for net ultrafiltration was only 0.34. The majority (75%) of patients had modeled urea and creatinine clearances that were within 20% of their measured values. These data suggest that the PD Adequest 2.0 for Windows program can predict urea and creatinine clearances with reasonable accuracy in pediatric PD patients, making it a valuable resource in prescription management.

Child↗

Validity and accuracy of a risk calculator in predicting periodontal disease.

BACKGROUND: Research on the pathobiology of periodontal diseases has increased our knowledge of these diseases and is fostering a transition from the repair model to the medical or wellness model of periodontal care. Successful application of the wellness model depends on an accurate and valid assessment of disease risk, as well as institution of risk reduction as an integral part of prevention and treatment. A computer-based risk assessment tool has been developed. METHODS: The authors reviewed clinical records and radiographs of 523 subjects enrolled in the Veterans Affairs Dental Longitudinal Study to evaluate the validity of risk prediction using the computer-based tool. Data from baseline examinations was entered into the risk calculator, and a risk score on a scale from 1 (lowest risk) to 5 (highest risk) was calculated for each subject to predict periodontal deterioration. Actual periodontal status in terms of alveolar bone loss (determined from digitized radiographs) and tooth loss (determined from clinical records) was assessed at years 3, 9 and 15. The authors determined the statistical strength of the association between risk prediction and actual outcome. RESULTS: The risk scores were strong predictors of periodontal status, as measured by alveolar bone loss and loss of periodontally affected teeth. Risk scores consistently ranked risk score groups from least to most bone loss and tooth loss. Compared with a risk score of 2, the relative risk of tooth loss was 3.2 for a risk score of 3, 4.5 for a risk score of 4 and 10.6 for a risk score of 5. CONCLUSIONS AND PRACTICE IMPLICATIONS: Use of the risk assessment tool over time may result in more uniform and accurate periodontal clinical decision-making, improved oral health, reduction in the need for complex therapy, reduction in health care costs and a hastening of the transition from a repair model to a wellness model of care.

Alveolar Bone Loss↗

Dynamic characterization of the molecular events during in vitro epidermal wound healing.

The aim of this study was to characterize some of the molecular events stimulated in vitro in response to injury within a confluent culture of normal epidermal keratinocytes as a model to understand the mechanisms of wound healing. To this end, an original device was developed specifically designed to perform calibrated injuries of great lengths within mono-stratified or pluri-stratified keratinocyte cultures. The experiments performed in this study validate this device as an appropriate tool for studying epidermal wound healing; this is because it performs mechanical injuries that stimulate the expression of multiple healing markers also known to be upregulated during wound healing in vivo (growth factors, cytokines, proteinases, extracellular matrix proteins). Using this device, it was demonstrated in human keratinocytes: mechanical injuries (i) immediately stimulate the tyrosine phosphorylation of numerous cellular proteins; (ii) induce molecular cascades leading to the activation of p21ras, mitogen-activated protein kinases, extracellular signal-regulated kinases 1/2, c-Jun NH2 terminal kinase, and p38 mitogen-activated protein kinase; and (iii) increase the phosphorylation of their respective substrates, c-jun and activator transcription factor 1. Wounding of these cells also results in increases in the DNA binding activities of several jun/fos activator protein-1 transcription factor complexes. It is important to note that the development of an appropriate wounding system was essential for performing this study, as use of a classical wounding procedure did not enable the detection of the biologic parameters reported above. In conclusion, these data indicate that using the appropriate system, it is possible to identify the signaling pathways activated in normal human keratinocyte cells after injury. In this study, it was shown that the mitogen-activated protein kinase pathways and activator protein-1 are stimulated in response to physical injury, and may be involved in regulating the expression of healing markers.

Cells, Cultured↗

Evaluation of Epilepsy Expert--a decision support system.

Epilepsy Expert is a decision support system based on the International Classification of Epilepsies and Epileptic Syndromes (1989). The aim of this study was to evaluate the Epilepsy Expert. First the diagnostic performance was validated. This was done in 3 stages: collection of the patient cases, determination of the 'correct diagnoses' and testing the system. How the users perceived the functionality of the system was studied by using an inquiry. Three physicians, experts of epilepsy, from different hospitals were asked to choose 10 patients. In the patient description was a short history, a detailed description of the seizure, EEG findings and their own diagnosis. Next, each expert made a diagnosis of the cases supplied by other experts by using the International Classification of Epilepsies and Epileptic Syndromes. The 'correct diagnosis' (so-called majority agreement) was the diagnosis given by the majority of the experts. The diagnosis of each expert was compared with the 'correct diagnosis'. The diagnoses obtained by the Epilepsy Expert were then compared with the 'correct diagnoses'. In the evaluation the expert physicians agreed on 37% of cases and all 3 disagreed on 17%. A majority agreed on 25 cases, which were used in the evaluation. In these 25 cases the experts' (A,B,C) diagnoses were correct or partly correct in 100, 64, 80% of cases, respectively. The program's diagnoses were correct or partly correct in 80% (module I) and 76% (modules IV and V) of cases. In the evaluation Epilepsy Expert was found to be only partly successful. The main reason for this was the weakness of the international classification. However, the program seems to be very close to the level of the experts. According to this limited inquiry Epilepsy Expert is not suitable for clinical use, because it is, for example, too simple and does not contain enough information.

Adult↗

Statistical brain mapping of 18F-FDG PET in Alzheimer's disease: validation of anatomic standardization for atrophied brains.

UNLABELLED: Despite the increased use of statistical mapping to detect brain functional changes in Alzheimer's disease (AD), potential artifacts introduced by stereotactic anatomic standardization of atrophied brains have not been examined carefully. We investigated the effects of anatomic standardization by Statistical Parametric Mapping (SPM) and NEUROSTAT. METHODS: First, 10 AD patients and 10 age-matched healthy volunteers underwent 18F-FDG brain PET imaging. Each image set was standardized to a stereotactic brain template using SPM or NEUROSTAT, followed by pixel normalization to the global or cerebellar activity. Within-group comparisons of standardized image sets by each method and a between-group comparison of healthy volunteers and AD patients were performed using the statistical analysis routines of SPM. Second, simulated PET image sets were generated from segmented MR image sets of 5 healthy volunteers and 5 AD patients. Using the anatomic standardization parameters estimated on the simulated image sets, original gray matter MR image sets were transformed to the stereotactic coordinate system. Between-group subtraction analyses of the transformed gray matter image sets between healthy volunteers and AD groups were performed to examine the accuracy of cortical gray matter matching. RESULTS: Between-group comparison by SPM or NEUROSTAT showed generally similar areas of hypometabolism in bilateral temporoparietal, posterior cingulate, and left frontal cortices. Both methods showed possible deformation artifacts in the anterior part of the corpus callosum. The localization of the peak hypometabolism varied considerably between the two methods when global normalization was applied. The use of a common brain template for standardization resulted in asymmetric differences in cortical margins, indicating systematic differences in the deformation algorithms. The realistic simulation study revealed gray matter mismatches to be 20% greater with SPM than with NEUROSTAT. CONCLUSION: Although different statistical mapping methods may yield grossly similar patterns of hypometabolism in AD, the extent, severity, and peak location of metabolic changes can be inconsistent. Deformation accuracy appears to be more prone to atrophy. These limitations need to be considered carefully in the application and interpretation of brain mapping analysis in atrophied brains.

Aged↗

Numerical criteria for the evaluation of ab initio predictions of protein structure.

As part of the CASP2 protein structure prediction experiment, a set of numerical criteria were defined for the evaluation of "ab initio" predictions. The evaluation package comprises a series of electronic submission formats, a submission validator, evaluation software, and a series of scripts to summarize the results for the CASP2 meeting and for presentation via the World Wide Web (WWW). The evaluation package is accessible for use on new predictions via WWW so that results can be compared to those submitted to CASP2. With further input from the community, the evaluation criteria are expected to evolve into a comprehensive set of measures capturing the overall quality of a prediction as well as critical detail essential for further development of prediction methods. We discuss present measures, limitations of the current criteria, and possible improvements.

Amino Acid Sequence↗

Evaluation of four monoclonal antibodies against HLA-B27 for their reliability in HLA-B27 typing with flow cytometry (FC): comparison with the classic microlymphocytotoxic test (MLCT).

Typing for HLA-B27 by serological methods is routinely performed using the microlymphocytotoxic test (MLCT). Since monoclonal antibodies (MAB) against HLA-B27 are available, flow cytometry (FC), which requires less time than the MLCT has been developed as an alternative technique. The aim of the present study was to check the accuracy and reliability of this method using different MAB against HLA-B27 in comparison to MLCT (using polyclonal antibodies against HLA-B27 and cross-reacting specificities [CRS]). FC was performed in 144 patients with HLA-B27-related rheumatic disorders (seronegative spondarthritides) using a special software package which requires corresponding calibration beads in order to achieve a standardized setup of the flow cytometer. MAB from the following producers were used: Becton & Dickinson (BD), Behringwerke (BE), One Lambda (OL), and Immunotech (IT). In addition to the critical limit of fluorescence intensity (FI) which indicates positivity if exceeded, provided by the software (but valid only for the MAB from BD), empirically twice the value of the STD calculated from the mean of the FI values of HLA-B27 positive patients was regarded a good cut off for the HLA-B27 positivity in FC measurements with the MAB used. Using a standard protocol including an incubation of whole EDTA-anticoagulated blood for 15 min with MAB against HLA-B27 (FITC-conjugated) and CD3 (PE-conjugated) and a lysis of erythrocytes, good discrimination between HLA-B27 positive and negative patients was obtained. Cross reactions with HLA-B27 positive patients occurred except when the MAB from OL was used. One false-negative result was found with OL's MAB (out of 22) and false-positive results occurred in HLA-B7+ patients when MAB from BD, BE, and IT were used. Unfortunately also 1 false-positive result (out of 57) was obtained in HLA-B7-, B27- patients with IT's MAB. Errors in the interpretation of the FC analysis might be avoided if more than one MAB (including those not cross reacting with HLA-B7) are used.

Antibodies, Monoclonal↗

Pedigree analysis package vs. MIXD: fitting the mixed model on a large pedigree.

Results of a simulation study with two methods of analysis of data simulated under the mixed model on a 232-member pedigree are presented. The programs Pedigree Analysis Package (PAP), which approximate the likelihoods needed in a complex segregation analysis, and MIXD, which uses Monte Carlo Markov chain (MCMC), to estimate likelihoods were used. PAP obtained unbiased estimates of the major locus genotype means and the gene frequency, but biased estimates of the environmental variance component, and thus the heritability. A substantial fraction of the runs did not converge to an internal set of parameter estimates when analyzed with PAP. MIXD, which uses the Gibbs sampler to perform the MCMC sampling, produced unbiased estimates of all parameters with considerably more accuracy than obtained with PAP, and did not suffer from convergence of estimates to the boundary of the parameter space. The difference in behavior and accuracy of parameter estimates between PAP and MIXD was most apparent for models with either high or low residual additive genetic variance. Thus in situations where accuracy of the model is important, use of MCMC methods may be useful. In situations where less accuracy is needed, approximation methods may be adequate. Practical issues in using MCMC as implemented in MIXD to fit the mixed model are also discussed. Results of the simulations indicate that, unlike PAP, the starting configurations of most parameter estimates do not substantially influence the final parameter estimates in analysis with MIXD.

Analysis of Variance↗

Software safety in medical applications.

The use of software in safety-critical medical applications permits sophisticated functionality that would otherwise not be achievable. However, it is very difficult to ensure that software in these systems is dependable. In particular all software development techniques have limitations, and none can provide any guarantee of overall software dependability. Given this shortcoming, the approach that we have taken is to develop techniques that emphasize the verification of properties that are important to overall software dependability. In this paper we describe two techniques that support the implementation and verification of dependable software for an experimental neurosurgical device and safety-critical applications in general. The first technique involves the assurance of critical safety properties by a relatively simple software component known as a safety kernel. Situated between the application software and the application devices, the safety kernel enforces rules that govern the safe operation of the devices. The simplicity of the safety kernel facilitates its implementation and verification. In most cases, it is not possible to rely on testing to provide the necessary verification of the software in a safety-critical application. However, testing can play an appropriate and vital role in the demonstration of safety properties. The second technique takes this approach, utilizing automated testing and selected test cases to demonstrate useful system properties.

Neurosurgery↗

Efficient electrostatic solvation model for protein-fragment docking.

A method is presented for the fast evaluation of the binding energy of a protein-small molecule complex with electrostatic solvation. It makes use of a fast preprocessing step based on the assumption that the main contribution to electrostatic desolvation upon ligand binding originates from the displacement of the first shell of water molecules. For a rigid protein, the precomputation of the energy contributions on a set of grids allows the estimation of the energy in solution of about 300 protein-fragment binding modes per second on a personal computer. The docking procedure is applied to five rigid binding sites whose size ranges from 17 residues to a whole protein of 107 amino acids. Using a library of 70 mainly rigid molecules, known micromolar inhibitors or close analogs are docked and prioritized correctly. The docking based rank-ordering of the library requires about 5 h and is proposed as a complementary approach to structure-activity relationships by nuclear magnetic resonance. Proteins 2001;42:256-268.

Binding Sites↗

Accuracy and precision of quantitative digital coronary arteriography: observer-, short-, and medium-term variabilities.

Coronary arteriograms are increasingly acquired and stored in digital format, which allows instantaneous review of the pictorial data during the cardiac catheterization procedure. To support the angiographer in choosing the optimal sizes of the recanalization devices and studying the efficacy of the recanalization procedures, we have developed a new analytical software package (Automated Coronary Analysis = ACA) on the Philips DCI (-SX) digital cardiac imaging system. The ACA-package allows the objective and reproducible assessment of the morphologic and functional severity of coronary obstructions. Required user interaction is limited to the definition of the start and end points of the coronary segment to be analyzed. Automated contour detection is based on the use of first and second derivative functions along scanlines perpendicular to the automatically computed vessel pathline in the first iteration and perpendicular to the initial contours in the second iteration. These derivative functions have been modified based on the line spread function of the X-ray imaging chain, which is of particular importance for the accurate measurement of small vessel sizes. Phantom studies have indeed demonstrated that vessel sizes down to 0.66 mm can be measured accurately and reproducibly. Inter- and intraobserver variability studies have demonstrated a variability in the obstruction diameter of 0.11 mm and 0.10 mm, respectively, and in the percent diameter stenosis of 5.64% and 3.18%, respectively. These variability studies have been extended to short-term studies with repeated acquisition in the same angiographic views after 5 min and to medium-term studies with repeated acquisition in the initial angiographic views at the end of the catheterization procedures. With these standardized repeated acquisition and analysis procedures, the variabilities in the obstruction diameters increased to 0.19 and 0.18 mm, respectively, and remained below 6% in the percent diameter stenosis (5.61% and 5.28%, respectively). With an analysis time of approximately 15 sec on the DCI-SX, an efficient tool is now available in the catheterization laboratory for the objective and reproducible assessment of vessel dimensions and changes therein as a result of recanalization procedures.

Coronary Angiography↗

Clinical evaluation of algorithms for ST measurement during exercise test.

HYPOTHESIS: Computer processing of the exercise electrocardiogram (ECG) has many advantages, but the reliability of the analysis algorithms is not easily evaluable. No standard annotated database, nor recommended practice for testing and reporting performance results is available: thus, performance evaluation of such devices can be accomplished only by using a set of unannotated recordings, obtained in clinical practice. We evaluated the accuracy of an original microcomputer-based exercise test analyzer comparing the ST computer output with the measurements obtained by two experienced cardiologists. METHODS: Six hundred ECG strips were randomly selected from the exercise test recordings of 60 patients. The ST shift (at J + 80 ms) was blindly assessed by two observers (with the aid of a calibrated lens) and compared with computer measurements. Correlation coefficients, linear regression equations, percent of discrepant measurements, and 95% confidence limits of the mean error were calculated for all leads, peripheral leads, precordial leads, and "stress-test" leads (II, III, aVF, V4, V5, V6). RESULTS: The computer did not analyze five samples on a total of 600 (0.83%) ECG strips because of excessive noise or signal loss, while 51 (8.5%) were considered unreadable by both observers and 67 (11.2%) were rejected by at least one observer. Correlation between the measurements taken by computer and observer(s) measurements was statistically significant (p < 0.001 for all lead groups), no systematic measurement bias was found, and the mean difference was lower than human eye resolution. CONCLUSIONS: Our algorithms provide results as good as those provided by trained cardiologists in measuring ST changes occurring during exercise test. However, this study did not evaluate whether computer improvement of the signal-to-noise ratio would allow accurate measurements even on cardiologists' uninterpretable ECG. This potential advantage of computer-assisted analysis could be assessed only by using a dedicated exercise test database, in which different patterns of noise are superimposed on noise-free recordings previously annotated for ST level.

Adult↗

Improved programs for the affected-pedigree-member method of linkage analysis.

The affected-pedigree-member (APM) method is a non-parametric method of linkage analysis, which requires no assumptions about how the trait of interest is inherited [Weeks and Lange, 1988, 1991, 1992; Lange and Weeks, 1990; Weeks et al., 1992]. The APM method uses only the affected members of each pedigree who are typed for the marker(s). Based on the affected members' marker genotypes and the relationships of the affecteds to each other, the APM method computes a statistic which provides a measure of marker similarity. If the affected members are significantly more similar at the marker locus than expected by chance, then one may conclude that the marker is not segregating independently of the disease. Since the APM method tests a hypothesis about marker similarity, and not about recombination between the marker and disease, it makes and requires no assumptions about the mode of inheritance of the disease. For this reason, the APM method has been used for complex diseases such as Alzheimer's, breast cancer, and melanoma [Pericak-Vance et al., 1989, 1990; Haile et al., 1990; Hall et al., 1990; St George-Hyslop et al., 1990; Cannon-Albright et al., 1992]. We would like to announce the availability of a much improved version of the APM program package. This version has been improved in several ways, as outlined below.

Bias↗