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Computational issues in mapping variation affecting susceptibility to complex disorders: the chicken and the egg.

Linkage mapping strategies for complex disorders have evolved under a variety of constraints. Some of these constraints reflect the nature of complex disorders and are manifest in limitations on the kinds of data that can be collected, while others were (at least historically) strictly computational. This paper focuses on how computational issues have impacted the design of studies on complex disorders and, conversely, how our study designs have influenced the computational issues that have been addressed. We now have unprecedented computational resources, but also face unprecedented computational and methodological challenges as we move from the linkage mapping of genes influencing susceptibility to complex disorders toward the identification of the actual variation affecting susceptibility to these disorders. The near-term computational and methodological issues we must address will be profoundly influenced by the study designs of the recent past. But future study designs, as well as our investments in computational and methodological research, ought to be developed considering the computational and informatics resources we now have at hand.

Algorithms↗

From computing with numbers to computing with words. From manipulation of measurements to manipulation of perceptions.

Interest in issues relating to consciousness has grown markedly during the last several years. And yet, nobody can claim that consciousness is a well-understood concept that lends itself to precise analysis. It may be argued that, as a concept, consciousness is much too complex to fit into the conceptual structure of existing theories based on Aristotelian logic and probability theory. An approach suggested in this paper links consciousness to perceptions and perceptions to their descriptors in a natural language. In this way, those aspects of consciousness which relate to reasoning and concept formation are linked to what is referred to as the methodology of computing with words (CW). Computing, in its usual sense, is centered on manipulation of numbers and symbols. In contrast, computing with words, or CW for short, is a methodology in which the objects of computation are words and propositions drawn from a natural language (e.g., small, large, far, heavy, not very likely, the price of gas is low and declining, Berkeley is near San Francisco, it is very unlikely that there will be a significant increase in the price of oil in the near future, etc.). Computing with words is inspired by the remarkable human capability to perform a wide variety of physical and mental tasks without any measurements and any computations. Familiar examples of such tasks are parking a car, driving in heavy traffic, playing golf, riding a bicycle, understanding speech, and summarizing a story. Underlying this remarkable capability is the brain's crucial ability to manipulate perceptions--perceptions of distance, size, weight, color, speed, time, direction, force, number, truth, likelihood, and other characteristics of physical and mental objects. Manipulation of perceptions plays a key role in human recognition, decision and execution processes. As a methodology, computing with words provides a foundation for a computational theory of perceptions: a theory which may have an important bearing on how humans make--and machines might make--perception-based rational decisions in an environment of imprecision, uncertainty, and partial truth. A basic difference between perceptions and measurements is that, in general, measurements are crisp, whereas perceptions are fuzzy. One of the fundamental aims of science has been and continues to be that of progressing from perceptions to measurements. Pursuit of this aim has led to brilliant successes. We have sent men to the moon; we can build computers that are capable of performing billions of computations per second; we have constructed telescopes that can explore the far reaches of the universe; and we can date the age of rocks that are millions of years old. But alongside the brilliant successes stand conspicuous underachievements and outright failures. We cannot build robots that can move with the agility of animals or humans; we cannot automate driving in heavy traffic; we cannot translate from one language to another at the level of a human interpreter; we cannot create programs that can summarize non-trivial stories; our ability to model the behavior of economic systems leaves much to be desired; and we cannot build machines that can compete with children in the performance of a wide variety of physical and cognitive tasks. It may be argued that underlying the underachievements and failures is the unavailability of a methodology for reasoning and computing with perceptions rather than measurements. An outline of such a methodology--referred to as a computational theory of perceptions--is presented in this paper. The computational theory of perceptions (CTP) is based on the methodology of CW. In CTP, words play the role of labels of perceptions, and, more generally, perceptions are expressed as propositions in a natural language. CW-based techniques are employed to translate propositions expressed in a natural language into what is called the Generalized Constraint Language (GCL). In this language, the meaning of a proposition is expressed as a generalized constraint, X isr R, where X is the constrained variable, R is the constraining relation, and isr is a variable copula in which r is an indexing variable whose value defines the way in which R constrains X. Among the basic types of constraints are possibilistic, veristic, probabilistic, random set, Pawlak set, fuzzy graph, and usuality. The wide variety of constraints in GCL makes GCL a much more expressive language than the language of predicate logic. In CW, the initial and terminal data sets, IDS and TDS, are assumed to consist of propositions expressed in a natural language. These propositions are translated, respectively, into antecedent and consequent constraints. Consequent constraints are derived from antecedent constraints through the use of rules of constraint propagation. The principal constraint propagation rule is the generalized extension principle. (ABSTRACT TRUNCATED)

Consciousness↗

[Methodological bases for using computer technologies in the activities of the medical service of the Armed Forces].

Authors state methodological bases of construction of automated control system (ACS) of the medical service of the Armed Forces and the Navy. A basis of the methodological rules is made by the analysis of conformity of the purpose (preservation and strengthening of the servicemen' health and management composed process: the tax, processing, storage and distribution of data and preparation of the decision, i.e. the information-and-target approach. The automation of processes of profile activity of forces and means of the medical service provides the constant control by functioning of medical units and institutions. The main targets of the ACS' functioning are processing of the information about quality of rendering of the medical care to the servicemen, its timeliness and profitability, productivity of their labour, conformity of work results to the medical standards and others. The quality and the efficiency of ACS'application is defined by a level of information maintenance. ACS of the medical service should be subsystem of the automated control system of the troops.

Computer Systems↗

Mathematical analysis of transport and consumption of molecules in heterogeneous brain tissue (methodology).

A computer model of metabolite transport and consumption in heterogeneous brain tissue, using a combination of probabilistic and deterministic techniques is being developed. The metabolites are put into two separate classes: (I) those that have reached a membrane for the first time during a small time step, delta t, and (II) those that have not yet reached a cell membrane for the first time during that time step. The time dependent spatial distribution of class (I) molecules is determined using random walk theory, which takes into account the actual paths of the molecules. The variation of the spatial distribution of class (II) molecules with time is determined using the time dependent diffusion equation with a boundary condition of zero concentration on the enclosing membrane boundaries.

Biological Transport, Active↗

Horizontal plane morphometry of normal and scoliotic vertebrae. A methodological study.

Computed tomography (CT) scans are widely used for quantification of the morphology of the vertebral body and of the changes of the thoracic cage in the horizontal plane in scoliosis. So far, however, no method exists for precise quantification of the parameters of the posterior elements. We present a method for quantification on the basis of CT scans of different parameters of the morphology of both the vertebral body and posterior elements in the horizontal plane. The precision and accuracy of the method were estimated in a model study by CT scanning of a normal and a scoliotic vertebra in different, controlled, tilted positions. Moreover, in a clinical study CT scans of 19 thoracic vertebrae from non-scoliotic subjects and the apex vertebra from 40 scoliotic subjects were selected to test the applicability of the method to clinical studies. The intra- and interobserver variation of the measurements was analysed. The angle between the longitudinal axis of the vertebral body and that of the whole vertebra was used to evaluate the asymmetry of the vertebral body. The right to left pedicle width index, the right to left hemi-canal width index and the index of transverse process angles related to the axis of the vertebra were used to quantify the asymmetry of the posterior elements. The results indicate that, except for the pedicle width index, the variables under study were not significantly influenced by a 5 degrees or 10 degrees tilt ventrally, dorsally, or laterally of either the normal or the scoliotic vertebra. Hence, the method can be satisfactorily applied to longitudinal group comparisons.(ABSTRACT TRUNCATED AT 250 WORDS)

Anthropometry↗

Bone mass determination from microradiographs by computer-assisted videodensitometry. I. Methodology.

The mass of hard-tissue specimens is assessed by optimised microradiography followed by computer-assisted videodensitometry. Radiographs are produced with 27 kV roentgen radiation, filtered through 0.5 to 1 mm of aluminium, on high-resolution glass plates. Aluminium step wedges are used for density calibration, the result being expressed as 'aluminium equivalent mass'. The plates are subjected to digital image analysis by an operator in interaction with a computer-based image processor, a television camera being used for image input. The program stored in the computer provides calibration of geometry and--via the step wedge images--of densitometry, background adjustment, etc. Measurement takes place by integration over the specimen-image area. No assumptions being needed concerning a specific attenuation model, the errors stemming from the common presumption of exponential attenuation are eliminated. Density profiles or maps of mass distribution are readily obtained from the computer. From measurements of aluminium phantom samples, the total random error (coefficient of variation) was determined at 1.8 per cent, the microradiographic and videodensitometric procedures contributing 1.6 per cent and 0.9 per cent, respectively, whereas the systematic error was negligible. Since specimens need not be sectioned, this method does not interfere with subsequent histologic preparation.

Bone and Bones↗

Applications of staffing, scheduling, and budgeting methodologies to hospital ancillary units.

A computer-aided methodology for integrating the budgeting, staffing, and labor productivity systems of Ancillary Services using Respiratory Therapy as an example is presented. The data needed, staffing computations and schedules, and productivity analysis are presented and discussed. A summary of the predicted savings and other benefits for the application hospital are presented with comparisons to present productivity systems.

Budgets↗

Methodologic trends in the healthcare professions: computer adaptive and computer simulation testing.

Assessing knowledge and performance on computer is rapidly becoming a common phenomenon in testing and measurement. Computer adaptive testing presents an individualized test format in accordance with the examinee's ability level. The efficiency of the testing process enables a more precise estimate of performance, often with fewer items than traditional paper-and-pencil testing methodologies. Computer simulation testing involves performance-based, or authentic, assessment of the examinee's clinical decision-making abilities. The authors discuss the trends in assessing performance through computerized means and the application of these methodologies to community-based nursing practice.

Clinical Competence↗

Evaluation of various imaging methods in the differential diagnosis of intraductal papillary-mucinous tumor (IPMT) of the pancreas.

BACKGROUND/AIMS: IPMT (intraductal papillary-mucinous tumor) of the pancreas has unique clinicopathological characteristics. The lesions which show characteristic clinical features of IPMT exhibit a wide spectrum of histological types ranging from atypical hyperplasia to invasive cancer. Therefore, surgical treatment cannot be recommended for all patients with IPMT. It is necessary to assess the malignant potential of IPMT in individual patients in order to select an appropriate approach. The aim of this study was to evaluate the effectiveness of endoscopic ultrasonography and intraductal ultrasonography as compared with ultrasonography and computed tomography for this purpose. METHODOLOGY: Ultrasonography, computed tomography, endoscopic ultrasonography and intraductal ultrasonography were performed in 49 cases of IPMT (atypical hyperplasia 7, adenoma 23, noninvasive 7 and invasive adenocarcinoma 12). On the basis of the histopathological analysis of another 28 cases of resected IPMT specimens, criteria for differential diagnosis by imaging modalities were defined as follows: Nonneoplastic lesion (atypical hyperplasia): no wall thickening or nodule; noninvasive IPMT (adenoma and intraductal carcinoma): a nodule or wall thickening is present; and invasive IPMT with pancreatic parenchymal invasion: a mass with a heterogenous pattern or interruption of the pancreatic duct wall by the mass. RESULTS: The diagnostic accuracy rate for differentiating nonneoplastic lesion noninvasive IPMT, and invasive IPMT was 33% by ultrasonography, 38% by computed tomography, 77% by endoscopic ultrasonography, and 67% by intraductal ultrasonography. Sensitivity, specificity and accuracy rates for differentiating neoplastic and nonneoplastic IPMT by ultrasonography was 33%, 100%, 42%, by computed tomography 36%, 100%, 44%, by endoscopic ultrasonography 90%, 71%, 88%, by intraductal ultrasonography 94%, 29%, 84%, respectively. Sensitivity, specificity and accuracy rates for differentiating invasive and noninvasive IPMT by ultrasonography was 25%, 100%, 80%, by computed tomography 33%, 100%, 83%, by endoscopic ultrasonography 55%, 97%, 88%, by intraductal ultrasonography 56%, 91%, 84%, respectively. Diagnostic accuracy for invasive IPMT except minimally invasive cases by endoscopic ultrasonography and intraductal ultrasonography was 80%, based on the results of the examination which demonstrated a higher grade lesion. CONCLUSIONS: With these criteria, ultrasonography and computed tomography showed high specificity, but low sensitivity for the differential diagnosis of neoplastic/nonneoplastic and invasive/noninvasive IPMT. However, endoscopic ultrasonography and intraductal ultrasonography had high sensitivity and diagnostic accuracy for the differential diagnosis of neoplastic/nonneoplastic lesions. Combination of endoscopic ultrasonography and intraductal ultrasonography showed a high accuracy rate in the diagnosis of invasive IPMT. Thus endoscopic ultrasonography and intraductal ultrasonography contributed significantly to the choice of the treatment for IPMT.

Adult↗

Computerized semen analysis (CASA): effect of semen concentration and chamber depth on measurements.

The purpose of this study was to examine the influence of sample concentration and chamber depth on the performance of a real-time analysis computer-assisted semen analysis system, the Hobson Sperm Tracker. Fresh semen samples were provided by patients or donors who attended the author's clinic. The samples were used to estimate total concentration, percentage motility, and sperm kinematics. A considerable variation was found in total concentration and motility recordings between manual and computerized analysis, which was more profound in high-density samples (>80 x 10(6) sperm/mL). The sperm motion parameters were significantly different between low- and high-density samples. This difference could not have been due to sample variation since it was also observed after 1:10 dilution of dense samples. The results indicate that a real-time analysis system can be used clinically for semen analysis over a wide range of sperm concentration. However, high sperm concentration can distort sperm count, motility, and sperm kinematics recordings.

Computing Methodologies↗

[Biological calculation methods and their application in pharmaceutical science].

This article gives an introduction to certain mathematical methods, that were developed with biological processes as model. Three methods are described: clustering and the more recently developed genetic algorithms and neural nets. Mainly the last two methods were applied first outside the medical and biological domain but are now used also in the medical and pharmaceutical sciences. There are many applications in the drug discovery field, but these methods are also becoming increasingly important in other domains of the pharmaceutical sciences (such as pharmaceutical technologies).

Algorithms↗

Object-oriented analysis and design: a methodology for modeling the computer-based patient record.

The article highlights the importance of an object-oriented analysis and design (OOAD) methodology for the computer-based patient record (CPR) in the military environment. Many OOAD methodologies do not adequately scale up, allow for efficient reuse of their products, or accommodate legacy systems. A methodology that addresses these issues is formulated and used to demonstrate its applicability in a large-scale health care service system. During a period of 6 months, a team of object modelers and domain experts formulated an OOAD methodology tailored to the Department of Defense Military Health System and used it to produce components of an object model for simple order processing. This methodology and the lessons learned during its implementation are described. This approach is necessary to achieve broad interoperability among heterogeneous automated information systems.

Abstracting and Indexing↗

Computational expansion of genetic networks.

We present a new methodology for computational analysis of gene and protein networks. The aim is to generate new educated hypotheses on gene functions and on the logic of the biological network circuitry, based on gene expression profiles. The framework supports the incorporation of biologically motivated network constraints and rules to improve specificity. Since current data is insufficient for de-novo reconstruction, the method receives as input a known pathway core and suggests likely expansions to it. Network modeling is combinatorial, yet data can be probabilistic. At the heart of the approach are a fitness function which estimates the quality of suggested network expansions given the core and the data, and a specificity measure of the expansions. The approach has been implemented in an interactive software tool called GENESYS. We report encouraging results in preliminary analysis of yeast ergosterol pathway based on transcription profiles. In particular, the analysis suggests a novel ergosterol transcription factor.

Algorithms↗

Evaluation of three methodologies for assessing work activity during computer use.

The overall goal of this study was to evaluate three separate methodologies for gathering work activity information among computer users. These methodologies included worker self-report, work sampling, and activity monitoring. A repeated measures design was employed whereby data were collected simultaneously on each subject (n = 51) across three consecutive workdays. Exposure information gathered included keying time, mouse usage, and time spent performing various work tasks (i.e., writing, proofreading, handling documents). Subjects were recruited to represent a wide range of keyboard activity and mouse usage. The study found that worker self-reports overestimated actual keyboard usage by a factor of approximately 1.5 for workers using the keyboard an average of 4 hours per day to a factor of 4 for workers using the keyboard an average of 30 min per day. On average, there was an approximate twofold difference between worker self-reported keying time and that obtained via activity monitoring and work sampling. This trend was similar with regard to time spent using the computer mouse. Worker self-reported mouse usage was approximately twofold higher than that obtained via activity monitoring or work sampling. Self-reported exposure information not only resulted in different estimates, but showed greater variance compared with the other methodologies. The results of this study suggest that the use of worker self-reported exposure information on keying time and mouse usage may not represent an accurate account of time spent performing these tasks. In the context of epidemiological studies work sampling and/or activity monitoring would be more suitable methodologies for obtaining such information.

Adult↗

Computer-assisted densitometric image analysis in periodontal radiography. A methodological study.

A videobased computer assisted densitometric image analysis (CADIA) system to quantify alveolar bone density changes on standardized dental radiographs was tested. An algorithm was used for grey level correction of a subsequent image to the baseline image. Quantitative information regarding positive and/or negative grey level changes were obtained automatically. Comparison of the ability of CADIA to detect surgically induced bone loss with interpretation of digital subtraction images and conventional radiographic interpretation revealed that CADIA was the most sensitive of the 3 methods, followed by interpretation of digital subtraction images which was considerably more sensitive than conventional radiographic interpretation. CADIA was capable of assessing differences in alveolar bone changes due to periodontal surgery between sites exposed to ostectomy/osteoplasty and control sites and sites exposed to periodontal surgery without ostectomy/osteoplasty. Finally, CADIA was capable of assessing differences in remodeling activity over 4-6 weeks after periodontal surgery between 45 surgical sites and 45 control sites. The system offers an objective method to quantitatively follow alveolar bone density changes over time and appears to be the most sensitive of previously described radiographic interpretation techniques.

Absorptiometry, Photon↗

Fundamentals of the model behind the COSMOS methodology used for team assessment in simulator training.

Team working is the basic way of working in the control rooms of hazardous technologies and therefore its quality is a safety-relevant issue. In addition to the technological competence it is also crucial for the crews to have the necessary communicational skills. During simulator training these skills can only be improved if the simulator use is embedded in an appropriate setting. To support this skill acquisition a computer-supported methodology called COSMOS (COmputer Supported Method for Operators' Self-assessment) has been developed. With its help more effective communication and more complete shared mental models can be fostered. This paper is a report on the psychological fundamentals and the mathematical model of the COSMOS methodology.

Communication↗