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Computer program to predict likelihood of finding and HLA-matched donor: methodology, validation, and application.

Approximately 65% of the patients requiring bone marrow transplantation do not have an HLA-A, -B, -DR identical sibling and therefore need to find a phenotypically matched unrelated donor. As of June 30, 1996, the National Marrow Donor Program maintains a registry of 2.31 million volunteer donors, 35% of whom are fully typed for HLA-A, -B, -DR loci. Because a majority of the donors has not been DR typed, a patient who does not find a complete match at the time of the preliminary search may elect to prospectively DR type A, B matched and A, B one-antigen mismatched donors. An efficient strategy is therefore needed for determining the likelihood that an appropriate donor exists and for deciding which of the donors that have not yet been DR typed should be tested for DR matching with the candidate. We developed a mathematical algorithm and computer program to facilitate the search for a suitable donor by donor race and phenotype. The program provides information on the likelihood of 1) finding at least one HLA-A, -B, -DR phenotypically matched donor, 2) the likelihood of finding at least one DR match among m A, B matched donors who have not yet been DR typed, and 3) the likelihood of an A, B one antigen mismatched donor of a specific phenotype being a DR match with the patient. The mathematical models underlying the program are based on basic population genetics theory and utilize HLA-A, -B, DR haplotype frequencies derived from the NMDP registry. The results of the validation study show that the prediction is highly accurate at the level of broad antigens. The algorithm and program have the potential to assist patients and physicians in optimizing their decisions regarding clinical management and resource allocation on the process of searching for a suitable unrelated bone marrow donor.

Blood Donors↗

Complementary mobile-phase optimisation for resolution enhancement in high-performance liquid chromatography.

An optimisation methodology in high-performance liquid chromatography (HPLC) is presented for the selection of two or more mobile phases having an optimal complementary resolution. The complementary mobile phases (CMPs) are selected in such a way that each one resolves optimally only some compounds in the mixture, while the remainder, resolved by the other mobile phase(s), can overlap among them. The methodology is based on the computation of a peak purity measurement for each solute, using an asymmetrical peak model for peak simulation. Two global resolution criteria (product of elementary resolutions and worst elementary resolution) and two methods for solving the problem (a systematic examination of all possible solute arrangements, and the use of genetic algorithms to expedite the calculation time) were used to find the optimal CMPs. The CMP optimisation methodology was applied to the resolution of a mixture of 10 diuretics and beta-blockers, which could not be resolved using a single mobile phase; virtual baseline resolution was achieved, however, with two CMPs.

Algorithms↗

Endoluminal repair of abdominal aortic aneurysm prevents enlargement of the proximal neck: a 9-year life-table and 5-year longitudinal study.

OBJECTIVE: Endoluminal repair of abdominal aortic aneurysm (AAA) is predicated on stability of the proximal neck of the aneurysm. Reports on morphologic changes in the proximal neck after endoluminal repair of AAA have thus far been limited in duration to 3 years or less. The aim of this study was to document changes in diameter of the proximal neck of AAA in a group of patients who had undergone endoluminal repair between 5 and 9 years previously. METHODS: Between May 1992 and December 1996, 61 patients with AAA were treated with endoluminal repair by the senior author. The following patients were excluded from the study group: those requiring primary conversion to open repair at the original operation (n = 8), those with false aneurysm (n = 1), and those with dissection in the proximal neck (n = 1). Fifty-one patients (48 men and three women) with a mean age of 71 years remained in the study group. The endoprostheses used were modified Parodi (n = 4), Endovascular Technologies (n = 14), White-Yu (n = 10), Stentor/Vanguard (n = 21), and Bard 1996 prototype (n = 2). Morphologic changes in the proximal aortic neck were studied with contrast computed tomographic scan with the methodology recommended by the Ad Hoc Committee for Standardized Reporting Practices for Endovascular AAA Repair (revised version). The maximum transverse diameter of the proximal neck was measured 1 cm below the most inferior renal artery. A Kaplan-Meier analysis was performed showing the proportion of patients at risk with a demonstrated enlargement of the neck at each interval of time compared with the predischarge computed tomographic scan. A longitudinal study of morphologic changes in the proximal aortic neck was also undertaken in 28 patients with successful endoluminal repair who survived 5 years. RESULTS: The Kaplan-Meier curve showed a probability of no dilatation of the proximal neck of 0.943 at 7 years after endoluminal AAA repair. Of 28 patients with 5 years of follow-up after discharge, only two had increases in the diameter of the proximal neck greater than 2 mm. The endograft in both patients had undergone migration before any proximal neck dilation. A paired t test showed that the overall average increase of 0.4 mm (standard error, 0.3 mm) in these 28 patients was not statistically significant (P =.23). CONCLUSION: A high probability (0.943 at 7 years) exists of no enlargement of the proximal neck of AAA after endoluminal repair. We hypothesize that endografts positioned correctly immediately below the renal arteries protect the proximal neck from dilatation in a manner that does not occur after open repair of AAA.

Aged↗

Application of a mixed normal mixture model for the estimation of Mastitis-related parameters.

The current methodology for estimating genetic parameters for SCC (SCS) does not account for the difference in SCS between healthy cows and cows with an intramammary infection (IMI). We propose a two-component finite mixed normal mixture model to estimate IMI prevalence, separate SCS subpopulation means, individual posterior probabilities of IMI, and SCS variance components. The theory is presented and the expectation-conditional maximization algorithm is utilized to compute maximum likelihood estimates. The methodology is illustrated on two simulated data sets based on the current knowledge of SCS parameters. Maximum likelihood estimates of IMI prevalence and SCS subpopulation means were close to simulated values, except for the estimate of IMI prevalence when both subpopulations were almost confounded. Individual posterior probabilities of IMI were always higher among infected than among healthy cows. Error and additive variance components obtained under the mixture model were closer to simulated values than restricted maximum likelihood estimates obtained assuming a homogeneous SCS distribution, especially when subpopulations were completely separated and when mixing proportion was highest. Convergence was linear and rapid when priors were chosen with caution. The advantages of the methodology are demonstrated, and its feasibility for large data sets is discussed.

Algorithms↗

A hybrid framework for 3D medical image segmentation.

In this paper we propose a novel hybrid 3D segmentation framework which combines Gibbs models, marching cubes and deformable models. In the framework, first we construct a new Gibbs model whose energy function is defined on a high order clique system. The new model includes both region and boundary information during segmentation. Next we improve the original marching cubes method to construct 3D meshes from Gibbs models' output. The 3D mesh serves as the initial geometry of the deformable model. Then we deform the deformable model using external image forces so that the model converges to the object surface. We run the Gibbs model and the deformable model recursively by updating the Gibbs model's parameters using the region and boundary information in the deformable model segmentation result. In our approach, the hybrid combination of region-based methods and boundary-based methods results in improved segmentations of complex structures. The benefit of the methodology is that it produces high quality segmentations of 3D structures using little prior information and minimal user intervention. The modules in this segmentation methodology are developed within the context of the Insight ToolKit (ITK). We present experimental segmentation results of brain tumors and evaluate our method by comparing experimental results with expert manual segmentations. The evaluation results show that the methodology achieves high quality segmentation results with computational efficiency. We also present segmentation results of other clinical objects to illustrate the strength of the methodology as a generic segmentation framework.

Algorithms↗

Quantifying arbitrary magnetic susceptibility distributions with MR.

Magnetic susceptibility, as a physical property of materials, plays important roles in many physical, chemical, engineering, and medical applications. Its quantification becomes of significant interest when MRI becomes a commonly used technique in biomedical applications. A general method is presented here for quantifying arbitrary magnetic susceptibility distributions in a localized region on the basis of first principles of magnetic induction field distributions in space. A proof of the concept was demonstrated by computer simulations. The study establishes the methodological basis for quantitative magnetic susceptibility imaging with MR.

Computer Simulation↗

Effect of sampling frequencies on the velocity of slow and fast phases of nystagmus.

A computer analysis of slow and fast phase of velocity of nystagmus is presented. Several methodological factors are known to affect the computation of velocities, such as sampling frequencies, cutoff frequencies of the differentiation method, and resolution in bits of analog-digital conversion. A simulated signal without noise was first applied in nystagmus data in order to study maximum velocities at the theoretical level. Electro-oculographic postrotational nystagmus movements were then examined to test theoretical results. It was shown that the sampling frequency ought to be 400 Hz at least, the cutoff frequency about 70 Hz, and the resolution of analog-digital conversion 12 bits or higher.

Diagnosis, Computer-Assisted↗

Computed tomography diagnosis of macrodystrophia lipomatosa.

Isolated congenital macrodactyly, termed macrodystrophia lipomatosa, is a rare entity. It may be confused with plexiform neurofibroma, hemangioma, or lymphangioma. Computed tomography provides an ideal methodology to verify the fatty proliferation of soft tissue that accompanies bone overgrowth and distinguishes this lesion from the others in the differential list.

Adipose Tissue↗

Defining neuroscience nursing practice: the 2001 role delineation study.

Studies that provided a blueprint for the Certified Neuroscience Registered Nurse (CNRN) examination were conducted in 1987, 1992, and 1997. In 2000, the American Board of Neuroscience Nursing (ABNN) formed a task force to re-examine the previous role delineation survey, obtain information to define current neuroscience nursing practice, and provide content validity for future CNRN examinations. Previous role delineation studies conducted by ABNN and a review of the literature provided the background for the study. The theoretical framework was the Nursing Intervention Classification (NIC) taxonomy and the methodology was a survey design. Computer Adaptive Technologies, Inc. (CAT), assisted the task force with survey development and data analysis. The survey, a three-part questionnaire, was mailed to 1,505 CNRNs and returned by 453 participants.

Certification↗

A method for meta-analysis where the level of data aggregation differs between studies.

BACKGROUND: This paper presents a statistical method that was used to assess haemoglobin levels world-wide among women, based on a combination of over 400 studies. METHODS: The methodology is easy to implement and is specifically adapted to the case where mean observations are taken, although the subgroups represented by the mean values may differ from study to study. That is, the level of data aggregation is not consistent between studies. RESULTS: In this example some studies report average haemoglobin levels for a sample of the population, while others give averages by urban/rural classification and/or pregnancy status. Though the method is based on likelihood principles, computation is straightforward. CONCLUSIONS: The methodology can be applied to a variety of meta-analytic situations where assessments are based on combining data from several sources. We provide an example of how the method was implemented in a study of haemoglobin levels among women undertaken at the World Health Organisation.

Data Collection↗

Physiological self-regulation of regional brain activity using real-time functional magnetic resonance imaging (fMRI): methodology and exemplary data.

A brain-computer interface (BCI) based on real-time functional magnetic resonance imaging (fMRI) is presented which allows human subjects to observe and control changes of their own blood oxygen level-dependent (BOLD) response. This BCI performs data preprocessing (including linear trend removal, 3D motion correction) and statistical analysis on-line. Local BOLD signals are continuously fed back to the subject in the magnetic resonance scanner with a delay of less than 2 s from image acquisition. The mean signal of a region of interest is plotted as a time-series superimposed on color-coded stripes which indicate the task, i.e., to increase or decrease the BOLD signal. We exemplify the presented BCI with one volunteer intending to control the signal of the rostral-ventral and dorsal part of the anterior cingulate cortex (ACC). The subject achieved significant changes of local BOLD responses as revealed by region of interest analysis and statistical parametric maps. The percent signal change increased across fMRI-feedback sessions suggesting a learning effect with training. This methodology of fMRI-feedback can assess voluntary control of circumscribed brain areas. As a further extension, behavioral effects of local self-regulation become accessible as a new field of research.

Adult↗

Virtual reality demonstration of surgical specimens, including links to histologic features.

The demonstration of surgical specimens, whether using 35-mm slides or digital images, tends to consist of the sequential presentation of images. Current digital technology permits a more flexible and effective way of communication, with the opportunity to more easily "navigate" between different aspects of specimens. We demonstrate a "virtual reality" method, based on QuickTime VR technology, that permits the interactive review of a complete profile of surgical specimens in the horizontal plane. Specimens were placed individually on a circular rotating platform. Thirty-six images of each specimen were captured using a digital camera, with rotation of the platform at 10 degrees intervals. The images were transferred to a computer and processed using specialized software (VRWorx). Histologic images were separately captured from tissue sections on glass slides using a digital camera mounted on a microscope. The final product is viewed using the QuickTime Viewer software application. A 360 degrees horizontal view of the specimens is achieved, with the capacity to actively rotate the specimen and to zoom in for closer review. Additionally, the user/presenter can click in predetermined "hot spots," which will open histologic images linked to those spots. This methodology, which uses readily available computer technology, helps provide a better three-dimensional understanding of surgical specimens and also a better correlation between gross and microscopic features.

Humans↗

A computer assisted photogrammetric analysis of soft tissue changes after orthodontic treatment. Part I: Methodology and reliability.

The purpose of this study was to use standardized facial photographs to compare the soft tissue profile changes in persons with Class II, Division 1 malocclusions who were treated with either an extraction or a nonextraction treatment modality. Ninety-one patients (44 extraction and 47 nonextraction) were evaluated with standardized facial photographs, available at pretreatment, posttreatment, and 2 years in retention. The photographs were digitized and displayed on a computer monitor. Thirty-eight landmarks (18 frontal and 20 lateral) were located. From these landmarks, 29 angular and linear dimensions (8 frontal and 21 lateral) were constructed. Descriptive and analytical statistics were used to compare the absolute dimensions, as well as the incremental changes, between the extraction and nonextraction groups. The present findings indicate that (1) Photographs allow for measurement of structures from a profile, as well as frontal orientations. (2) Measurement of profile changes from facial photographs appear to be fairly reliable but also have significant limitations. (3) Certain landmarks tended to be less reliable than others, e.g., subnasale and gnathion. In general, measurements from frontal photographs were more reliable than those obtained from lateral photographs and linear measurements were more reliable than angular measurements. (4) Changes in head posture within the cephalostat have an impact on vertical facial dimensions measured from frontal photographs. Horizontal dimensions were effected to a lesser degree. (5) Facial structures that lie closer to the camera appeared to be relatively larger than structures located farther from the camera. (6) The overall process of evaluating facial changes from photographs is both technique and operator sensitive. (7) More research specifically testing the photogrammetric method in a clinical setting is needed.

Adolescent↗

Computer-aided S-phase fraction determination in DNA static cytometry in breast cancer. A preliminary methodologic study on cytologic material.

This methodologic study was performed on a single-cell-cycle breast carcinoma to evaluate the feasibility of computer-aided S-phase fraction determination in DNA static cytometry. The investigation was performed on Feulgen-stained cytologic material in which the total optical density values of 1,000 consecutive, randomly selected nuclei were analyzed (MultiCycle software). A good correlation in the S-phase fraction value with flow cytometry was obtained when the G2/G1 ratio was fixed at 1.95, when the histogram data points were smoothed at least once and the coefficient of variation of the G2 peak was the same as that of G0-G1 or when a first-order S-phase polynomial model was used. The percentages of nuclei in G0-G1 and G2 were somewhat similar to those obtained with flow cytometry. The greatest discrepancy with flow cytometry was observed in the value of the coefficient of variation of the G0-G1 peak of the static cytometric data: it was at least twice as great. It always remained high despite the software options used. As for the influence of the sample size in the S-phase calculation, the software was also run on samples of 600 and 200 nuclei. When the G2/G1 ratio was fixed at 1.95, the data obtained from 600 nuclei did not differ from those obtained with 1,000 nuclei, whereas an analysis on 200 nuclei showed a substantial variation. The software also allowed calculation of the ratio of the G0-G1 peak of the neoplastic population against that of the diploid reference (DNA index), the value of which in flow cytometry was 1.0.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗

Computer control of mechanical ventilation.

Computer control of mechanical ventilators includes the operator-ventilator interface and the ventilator-patient interface. New ventilation modes represent the evolution of engineering control schemes. The various ventilation control strategies behind the modes have an underlying organization, and understanding that organization improves the clinician's appreciation of the capabilities of various ventilation modes and gives an idea of what we can and should expect for the future. The operator-ventilator interface has received little attention in the literature, despite the fact that there is a whole science of human-computer interaction. This report suggests a methodology for the study of ventilator interfaces.

Artificial Intelligence↗

[Bayesian estimation of pharmacokinetic parameters of etoposide].

Studies of the relationships between the pharmacokinetics of a drug and its pharmacodynamics could significantly improve chemotherapy efficacy. However, despite their proven value, pharmacokinetic studies sometimes appear as cumbersome and difficult procedures. The bayesian approach associated with an optimal sampling time strategy (OST) allows the determination of the pharmacokinetic parameters of a drug with a smaller number of blood samples compared with that required by the classic maximum likelihood estimation (MLE). Therefore, the bayesian approach may lead to a less discomfort to the patients and less work for the medical staff. Such a method was developed to determine the individual pharmacokinetic parameters of etoposide (VP16). First, the statistical characteristics of the pharmacokinetic parameters were evaluated in 14 courses from 14 patients. Then, based on these results, a three-sample strategy was developed. Validation of this methodology was performed in 7 new patients and evaluated by computing bias and precision. The performance of the developed methodology shows that it could successfully be applied for the determination of VP16 pharmacokinetic parameters.

Adult↗

Modelling the world in real time: how robots engineer information.

Programming robots and other autonomous systems to interact with the world in real time is bringing into sharp focus general questions about representation, inference and understanding. These artificial agents use digital computation to interpret the data gleaned from sensors and produce decisions and actions to guide their future behaviour. In a physical system, however, finite computational resources unavoidably impose the need to approximate and make selective use of the information available to reach prompt deductions. Recent research has led to widespread adoption of the methodology of Bayesian inference, which provides the absolute framework to understand this process fully via modelling as informed, fully acknowledged approximation. The performance of modern systems has improved greatly on the heuristic methods of the early days of artificial intelligence. We discuss the general problem of real-time inference and computation, and draw on examples from recent research in computer vision and robotics: specifically visual tracking and simultaneous localization and mapping.

Artificial Intelligence↗

Variances and covariances of squared linkage disequilibria in finite populations.

Analysis of linkage disequilibrium D among restriction sites or bases in DNA sequences, arising from mutations in finite populations, depends on a knowledge of the variance-covariance structure of measures such as D2 between different pairs of sites. This requires evaluation of the eighth moments of gene frequencies among two, three, and four loci, and the necessary methodology is derived here and results are computed. While primary emphasis is placed on disequilibrium arising from mutation or gene conversion, the methodology also allows for the joint effects of only drift and recombination. Numerical results confirm that squared linkage disequilibria can have high variances and covariances.

Base Sequence↗