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PubMed1998

Statistical methodology: VII. Q-methodology, a structural analytic approach to medical subjectivity.

Q-methodology is a relatively unknown tool to medical researchers, that uses a mixed quantitative/qualitative statistical technique known as by-person factor analysis to study subjectivity. Q-methodology allows the grouping of individuals according to their subjective feelings about a topic, without requiring preconceived ideas regarding the structure of those subjective feelings. Q-methodology is demonstrated using a study in which attitudes of emergency medicine residents toward computer education are explored systematically and classified in terms of statistically distinct factor viewpoints. In this example, Q-methodology identifies 4 attitude groups, as related to computers and computer education: 1) interested, eager to learn; 2) frustrated and interested, but with reservations; 3) interested mainly in benefits, willing to expend minimal effort; and 4) knowledgeable, independent learner. Q-methodology can be used to determine the structure of attitudes on a subjective topic, often yielding new insights.

Attitude↗
PubMed1976

A computer program for the generalized chi-square analysis of categorical data using weighted least squares (GENCAT).

GENCAT is a computer program which implements an extremely general methodology for the analysis of multivariate categorical data. This approach essentially involves the construction of test statistics for hypotheses involving functions of the observed proportions which are directed at the relationships under investigation and the estimation of corresponding model parameters via weighted least squares computations. Any compounded function of the observed proportions which can be formulated as a sequence of the following transformations of the data vector--linear, logarithmic, exponential, or the addition of a vector of constants--can be analyzed within this general framework. This algorithm produces minimum modified chi-square statistics which are obtained by partitioning the sums of squares as in ANOVA. The input data can be either: (a) frequencies from a multidimentional contingency table; (b) a victor of functions with its estimated covariance matrix; and (c) raw data in the form of integer-valued variables associated with each subject. The input format is completely flexible for the data as well as for the matrices.

Biometry↗
PubMed2006

A non-invasive tissue-specific molecular delivery method of cancer gene therapy.

A Japanese word, monozukuri (literally translated "making things") is the philosophy of first having the idea and then the faith in the technical expertise and experience to accomplish the result. We believe that the concept of engineering is monozukuri. Through the process of monozukuri, engineered natural science based on mathematics and physics has been developed. Medicine is the field of study which has been developed for maintaining daily healthy life with diagnosis, treatment, examination, and protection. Biomedical engineering is the interdisciplinary study of engineering and medicine, and should be developed based on monozukuri. In this particular research, we have developed a physical molecular delivery method for cancer gene therapy using nano/microbubbles and ultrasound. First, the behavior of cavitation bubbles and subsequent shock wave phenomena involved in the mechanism of molecular delivery were analyzed, combining theory and computer simulation. In a second step, the methodology was optimized in vitro and in vivo. Finally, the therapeutic potential of the method in pre-clinical models was evaluated using transgenes relevant to cancer gene therapy instead of reporter genes, and whole body, non-invasive imaging using single photon emission computed tomography (SPECT/CT) was used to evaluate the selectivity of gene delivery in vivo.

Animals↗
PubMed2004

A computational TW3 classifier for skeletal maturity assessment. A Computing with Words approach.

This paper proposes a fuzzy methodology to translate the natural language descriptions of the TW3 method for bone age assessment into an automatic classifier. The classifier is built upon a modified version of a fuzzy ID3 decision tree. No large data records are needed to train the classifier, i.e., to find out the classification rules, since the classifier is built upon rules given by the TW3 method. Only small data records are needed to fine-tune the fuzzy sets used to implement the rulebase.

Adolescent↗
PubMed2002

Exploring genetic regulatory networks in metazoan development: methods and models.

One of the foremost challenges of 21st century biological research will be to decipher the complex genetic regulatory networks responsible for embryonic development. The recent explosion of whole genome sequence data and of genome-wide transcriptional profiling methods, such as microarrays, coupled with the development of sophisticated computational tools for exploiting and analyzing genomic data, provide a significant starting point for regulatory network analysis. In this article we review some of the main methodological issues surrounding genome annotation, transcriptional profiling, and computational prediction of cis-regulatory elements and discuss how the power of model genetic organisms can be used to experimentally verify and extend the results of genomic research.

Animals↗
PubMedDate not supplied

Percutaneous drainage under real-time computed tomography-fluoroscopy guidance.

BACKGROUND/AIMS: The goal of our study was to assess the use of real-time computed tomography-fluoroscopy guidance for percutaneous drainage of abnormal thoracic, abdominal, and pelvic fluid collections. METHODOLOGY: The subjects were 32 patients who underwent 36 percutaneous computed tomography-fluoroscopy guided thoracic, abdominal, and pelvic drainage procedures to drain abscess (n=29), fluid collection after pancreatitis (n=3), lymphocyst after gynecological surgery (n=3), and the gallbladder transhepatically (n=1) between September 1997 and August 2003. The patient population was 28-86 years old and consisted of 19 men and 13 women. The drainage methods included a Seldinger's technique with a guidewire and serial dilators in every case. The procedures were guided by using a helical computed tomography scanner that provided real-time fluoroscopy reconstruction. RESULTS: Percutaneous drainage under real-time computed tomography-fluoroscopy guidance was successfully performed in every procedure. Real-time computed tomography-fluoroscopy allowed rapid assessment of needle, guidewire, dilator, and catheter placement. The only drainage-induced complication encountered was a subcutaneous hematoma after one procedure (2.8%). No patients had serious complications. The average procedure time was 32 minutes. CONCLUSIONS: Computed tomography-fluoroscopy is a useful method for guiding the accurate and safe drainage of abnormal thoracic, abdominal, and pelvic fluid collections.

Abscess↗
PubMed1986

Semiautomatic microscopy as a tool for cytologists.

Despite impressive advances in the application of computer image analysis to cytology, many of the identification tasks that cytologists are called on to perform remain refractory to automated image analysis. The major reason is that a large fraction of these images, though simple for a human to deal with, are too complex to yield to current image analysis methodologies. It may be years before automated computer image analysis is reduced to clinical practicality. Even then, it is not clear that all cytologic image analyses will prove amenable to automation. In the meantime, semiautomatic image analysis (computer-aided microscopy) can provide a viable alternative, especially to persistently difficult image analysis problems. In semiautomatic image analysis, the onerous tasks of data acquisition--e.g., stage movement, data entry and storage--are left to the computer, while the decision-making tasks-e.g., identifying a cell's morphologic class--are left to the observer. Such a system proves to be easy and flexible to use as well as economical to build. It can also provide a reliable data base for the later evaluation of fully automated systems as they are developed. One such semiautomatic system, the Image Combining Computer Microscope (ICCM), is described, and the range of its application is illustrated. Some of the examples of ICCM applications discussed are: neuronal cell plots, three-dimensional dendrite tracking, serial section reconstruction of axons and mapping of plaques and tangles in Alzheimer's disease. They illustrate how powerful a semiautomated system can be in handling complex image analysis problems. It is suggested that semiautomated image analysis provides a viable long-range alternative to many cytologic image analysis problems.

Alzheimer Disease↗
PubMed2005

Respiratory correlated cone-beam computed tomography on an isocentric C-arm.

A methodology for 3D image reconstruction from retrospectively gated cone-beam CT projection data has been developed. A mobile x-ray cone-beam device consisting of an isocentric C-arm equipped with a flat panel detector was used to image a moving phantom. Frames for reconstruction were retrospectively selected from complete datasets based on the known rotation of the C-arm and a signal from a respiratory monitor. Different sizes of gating windows were tested. A numerical criterion for blur on the reconstructed image was suggested. The criterion is based on minimization of an Ising energy function, similar to approaches used in image segmentation or restoration. It is shown that this criterion can be used for the determination of the optimal gating window size. Images reconstructed from the retrospectively gated projection sequences using the optimal gating window data showed a significant improvement compared to images reconstructed from the complete projection datasets.

Equipment Design↗
PubMed1984

Computer-assisted morphometry and microdensitometry of transmitter- identified neurons with special reference to the mesostriatal dopamine pathway. Methodological aspects.

New morphometrical and microdensitometrical approaches for evaluation of transmitter-identified neurons in the central nervous system have been developed. These rely at the presynaptic level on the use of immunocytochemistry and at the postsynaptic level on the use of receptor autoradiography. The immunocytochemical analysis involves the indirect immunofluorescence method and the indirect immunoperoxidase method utilizing cryostat and vibratome sections, respectively. In the postsynaptic analysis cryostat sections and tritium-sensitive film were employed. A block diagram representation of the system of the image analyzer used and its connection with its host computer is given. Furthermore, flow charts of the original software developed by our group in presented. The morphometrical analysis has been performed on coronal sections of rat brain resulting in determinations of cell body and cell group parameters. Based on this information, objective criteria have been introduced to assess the existence of a cell group of transmitter-identified neurons in a three-dimensional frame and to give a morphometrical description of this group in the space. Moreover, new quantitative approaches to describe the dendritic and terminal fields have been introduced and for the first time in this type of morphometrical analysis, the Lorenz curves and the Gini index have been utilized in the description of the pattern of dendritic and terminal networks. By means of these morphometrical approaches it became possible to analyze topological and biochemical heterogeneities within cell groups defined in the rostrocaudal frame. In particular, it has been possible to develop a quantitative method for the evaluation of coexistence in nerve cell bodies. This method has been called the overlap method and allows an analysis cell by cell of the possible coexistence of two or more antigens.

Animals↗
PubMed2004

Estimating three-class ideal observer decision variables for computerized detection and classification of mammographic mass lesions.

We are using Bayesian artificial neural networks (BANNs) to classify mammographic masses in schemes for computer-aided diagnosis, and we are extending this methodology to a three-class classification task. We investigated whether a BANN can estimate ideal observer decision variables to distinguish malignant, benign, and false-positive computer detections. Five features were calculated for 63 malignant and 29 benign computer-detected mass lesions, and for 1049 false-positive computer detections, in 440 mammograms randomly divided into a training and testing set. A BANN was trained on the training set features and applied to the testing set features. We then used a known relation between three-class ideal observer decision variables and that used by a two-class ideal observer when two of three classes are grouped into one class, giving one decision variable for distinguishing malignant from nonmalignant detections, and a second for distinguishing true-positive from false-positive computer detections. For comparison, we grouped the training data into two classes in the same two ways and trained two-class BANNs for these two tasks. The three-class BANN decision variables were essentially identical in performance to the specifically trained two-class BANNs, with the average difference in area under the ROC curves being less than 0.0035 and no differences in area being statistically significant. Thus, the BANN outputs obey the same theoretical relationship as do the three-class and two-class ideal observer decision variables, which is consistent with the claim that the three-class BANN output can provide good estimates of the decision variables used by a three-class ideal observer.

Breast Neoplasms↗
PubMed1980

Influence of analytical quality on the diagnostic power of a single S-CK B test in patients with suspected acute myocardial infarction.

We have compared tow theoretical methods for assessing the effects of changing analytical quality of a clinical chemical test. The test considered was S-creatine kinase B subunit activity, used as the only diagnostic criterion for acute myocardial infarction. The two methods applied were based on (i) graphical analysis, and (ii) computer simulation. The results comprise the effects of changing analytical imprecision and bias on the weighted sum of misclassified cases on basis of the test results. The two methods yield comparable results at high analytical imprecision, but due to differences in assumptions about the error distribution of test results the difference increases with increased analytical imprecision. The graphical analysis is easily performed but is restricted in possible applications. The computer simulation is not a generally available methodology, but allows for mixing of different types of statistical distributions, which is not the case in conventional variance analysis.

Chemistry Techniques, Analytical↗
PubMed1997

Surface electromyography and mouse use position.

This study examines muscle tension and subjective muscle tension awareness while using a computer mouse positioned to the right of a standard computer keyboard and a centrally positioned trackball. Seventeen volunteer subjects experienced in mouse and trackball use were seated at an ergonomically adjusted workstation. Surface electromyography (sEMG) and subjective muscle tension levels were recorded from four muscle groups (left sternocleidomastoid/scalene, right upper trapezius, right posterior deltoid, and right lower trapezius/rhomboids) during 1-min trials with subjects resting with hands in their lap, while using a trackball below the centre of the keyboard, and while using a mouse immediately to the right of a 101-key keyboard. All subjects showed significantly higher mean sEMG activity recorded from the right upper trapezius, right posterior deltoid, and right lower trapezius/rhomboids during mouse use to the right of a standard keyboard (arm abducted) compared to using a trackball positioned centrally, (p < 0.001). sEMG levels remained elevated during the entire trial period of right side mouse use without evidence of microbreaks (< 1 s epochs of low sEMG activity). sEMG activity from the left sternocleidomastoid/scalene muscles showed no significant change from baseline in any condition. Subjective reports of muscle tension did not correlate with sEMG activity. The authors predict that there will be an overall increase in reports of upper extremity musculoskeletal disorders (UEMSD) and computer related disorders (CRD) when people abduct their arms in order to reach a mouse positioned to the side of standard width, or wider keyboards. Discussed are the applications of sEMG for evaluation of computer keyboard and pointing device use, appropriate ergonomic equipment design, and a methodology for improving muscle awareness, strengthening, relaxation, and workstyle practices to promote healthier computing.

Adult↗
PubMed2026

Computational strategies for copy number variation detection, disease association, and beyond.

Copy number variations (CNVs) are key structural variations that contribute to human genetic diversity, evolution, and disease susceptibility. Advances in sequencing technologies and computational methods have improved CNV detection, yet association studies remain challenged by methodological limitations and a lack of standardisation. This review provides an overview of computational strategies for germline CNV detection and disease association. We highlight the value of CNV analysis for uncovering genetic contributions to complex traits and disease risk and outline an analysis workflow including key benchmarking methods. We also discuss current challenges and future directions for advancing CNV detection and association analysis.

Humans↗
PubMed2005

A protocol for building and evaluating predictors of disease state based on microarray data.

MOTIVATION: Microarray gene expression data are increasingly employed to identify sets of marker genes that accurately predict disease development and outcome in cancer. Many computational approaches have been proposed to construct such predictors. However, there is, as yet, no objective way to evaluate whether a new approach truly improves on the current state of the art. In addition no 'standard' computational approach has emerged which enables robust outcome prediction. RESULTS: An important contribution of this work is the description of a principled training and validation protocol, which allows objective evaluation of the complete methodology for constructing a predictor. We review the possible choices of computational approaches, with specific emphasis on predictor choice and reporter selection strategies. Employing this training-validation protocol, we evaluated different reporter selection strategies and predictors on six gene expression datasets of varying degrees of difficulty. We demonstrate that simple reporter selection strategies (forward filtering and shrunken centroids) work surprisingly well and outperform partial least squares in four of the six datasets. Similarly, simple predictors, such as the nearest mean classifier, outperform more complex classifiers. Our training-validation protocol provides a robust methodology to evaluate the performance of new computational approaches and to objectively compare outcome predictions on different datasets.

Algorithms↗
PubMed2001

Use of computer-assisted sperm motility assessment and multivariate pattern analysis to characterize ejaculate quality in Mohor gazelles (Gazella dama mhorr): effects of body weight, electroejaculation technique and short-term semen storage.

Subjective and objective semen assessments were performed on 18 male Mohor gazelles (Gazella dama mhorr). Sperm motility assessments combined with sperm plasma membrane and acrosomal integrity evaluations were undertaken as part of a captive breeding programme. The primary objective was to test methodology for short-term preservation of gazelle semen for artificial insemination (storage in N-[Tris(hydroxymethyl)methyl]-2-aminoethanesulphonic acid-Tris diluent (TEST) for up to 96 h at 17 degrees C). However, the secondary objective was to investigate phenotypic and genotypic influences on semen quality within this small population, which was established in 1971 with only 12 genetic founders. Sperm motility was measured by computer-assisted semen assessment and the data were analysed using a pattern analysis technique to detect and quantify naturally occurring sperm subpopulations within the semen samples. Four sperm subpopulations distinguishable by their motion characteristics were detected. The relative frequencies of two subpopulations (population 2: highly motile, non-linear; and population 4: poorly motile, non-linear) in fresh semen were correlated with the maximum voltage used during electroejaculation. The frequency of subpopulation 2 was negatively correlated with maximum voltage (r = -0.875, P < 0.0001) and the frequency of subpopulation 4 was positively correlated (r = 0.727, P < 0.005). The frequencies of all subpopulations varied significantly among the animals sampled (chi-squared = 2577.6, degrees of freedom = 54, P < 0.0001) and subpopulation 4 was also correlated with body weight (r = -0.59, P < 0.005). Semen stored at 17 degrees C retained motility, plasma membrane and acrosomal integrity for 48 h, but these measures decreased thereafter. The frequency of a sperm subpopulation showing uncoordinated but active motility increased significantly over the first 48 h and then decreased.

Animals↗
PubMed2005

Matching-pursuit/split-operator-Fourier-transform computations of thermal correlation functions.

A rigorous and practical methodology for evaluating thermal-equilibrium density matrices, finite-temperature time-dependent expectation values, and time-correlation functions is described. The method involves an extension of the matching-pursuit/split-operator-Fourier-transform method to the solution of the Bloch equation via imaginary-time propagation of the density matrix and the evaluation of Heisenberg time-evolution operators through real-time propagation in dynamically adaptive coherent-state representations.

Journal Article↗