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Visualization and evaluation of clusters for exploratory analysis of gene expression data.

Clustering algorithms have been shown to be useful to explore large-scale gene expression profiles. Visualization and objective evaluation of clusters are two important considerations when users are selecting different clustering algorithms, but they are often overlooked. The developments of a framework and software tools that implement comprehensive data visualization and objective measures of cluster quality are crucial. In this paper, we describe a theoretical framework and formalizations for consistently developing clustering algorithms. A new clustering algorithm was developed within the proposed framework. We demonstrate that a theoretically sound principle can be uniformly applied to the developments of cluster-optimization function, comprehensive data-visualization strategy, and objective cluster-evaluation measures as well as actual implementation of the principle. Cluster consistency and quality measures of the algorithm are rigorously evaluated against those of popular clustering algorithms for gene expression data analysis (K-means and self-organizing maps), in four data sets, yielding promising results.

Algorithms↗

Dual-peak dose measurement for radiochromic films by a newly developed spectral microdensitometer.

Radiochromic film (RCF) dosimetry is usually based on densitometric methods which use an analyzing light source of a fixed or a broad spectrum of wavelengths. These methods have not exploited the sensitivity of the dose response of the RCF otherwise attainable by using a light source with wavelengths peaked at the two absorption peaks in the absorption spectrum of the RCF. A new algorithm of dual-peak dose measurement for the RCF has been proposed in this paper to make use of these dual absorption peaks to achieve the maximum attainable sensitivity. This technique relies on the measurement of the transmittance of the RCF at the wavelength of the major and minor absorption peaks, respectively. The dual-peak dose measurement is accomplished with the aid of a novel spectral microdensitometer developed in our Institute. The microdensitometer utilizes a monochromator to provide a light source of which the wavelength can be matched precisely to the wavelength of the absorption peaks of the RCF. The doses obtained at these wavelengths are fed into a weighted objective function and an optimum dose is searched by minimizing the objective function to give the best estimate of the dose deposited on the film. An initial test shows that there is a good agreement between the estimated and actual dose deposited; and the maximum discrepancy was found to be less than 1%.

Algorithms↗

A new single-fibre laser Doppler flowmeter based on digital signal processing.

A new laser Doppler flowmeter, based on a personal computer with a digital signal processor for detecting the blood perfusion in skeletal muscle, was designed and evaluated. An infrared laser diode (750 nm) fed a single optical fibre, 400 microns in diameter, which was introduced into the muscle. A PC equipped with a digital processing unit was used for emulation of the laser Doppler algorithm and for presentation of the measurement results. The Doppler signal power spectral density and corresponding flow values were visualized on the computer screen continuously in real-time, and could also be saved on the hard disk for off-line analyses. The graphic-user interface supported by Labwindows software made the system easy to use. It is possible to alter in the software the signal processing and the ways in which the signals and results are presented. The new system was evaluated by using a flow model as well as a mechanical model. The model studies showed linear relationships between particle velocity and flow in the range of 0-5 mm s-1. The system was also tested in measurements of the blood flow in the brachioradial muscle, and was found to have advantages over our previously used systems.

Algorithms↗

Application of the ART-2a algorithm to laser ablation aerosol mass spectrometry of particle standards.

Single-particle mass spectrometers are now commonly used to analyze atmospheric particles and generate tens of thousands of spectra from typical measurement campaigns. The ART-2a spectrum algorithm has been used to classify these spectra. In this work, we generate a range of particles that are models of those that are common in the atmosphere. A single-particle mass spectrometer is used to analyze these known particles, and the spectra are classified using ART-2a. The optimum vigilance parameter is approximately 0.5 while the optimum learning rate is approximately 0.05. The classifications elucidate limitations in generation of test particles, their analysis by single-particle techniques, and their classification by ART-2a.

Journal Article↗

Influence of angle between the nozzle and skin surface on the heat flux and overall heat extraction during cryogen spray cooling.

High speed video imaging and an inverse heat conduction problem algorithm were used to observe and measure the effect of the angle between the nozzle and surface of a skin phantom on: (a) surface temperature; (b) heat flux q; and (c) overall heat extraction Q during cryogen spray cooling (CSC). A skin phantom containing a fast-response temperature sensor was sprayed with 50 ms cryogen spurts from a commercial nozzle placed 30 mm from the surface. The nozzle was systematically positioned at angles ranging from 5 to 90 degrees (perpendicular) with respect to the phantom surface. It is shown that angles as low as 15 have an insignificant impact on the surface temperature, q and Q. Only exaggerated angles of 5 show up to 10% lower q and 30% lower Q with respect to the maximal values measured when nozzles are aimed perpendicularly. This study proves that the slight angle that many commercial nozzles have does not affect significantly the CSC efficiency.

Algorithms↗

Quantification of global and regional renal blood flow with electron beam computed tomography.

Alterations in renal blood flow distribution may occur in a variety of pathophysiologic situations; however, quantification of global and regional renal blood flows has been limited because of the lack of reliable, noninvasive techniques. To determine the feasibility of flow measurements with electron-beam computed tomography (EBCT), six anesthetized dogs were scanned by EBCT during basal conditions, after renal vasodilation, and at recovery. Flow (mL/min/cm3 tissue) was calculated from EBCT-derived time-density curves using three different algorithms and compared with simultaneously obtained electromagnetic flow (EMF) probe measurements after indexing to EBCT-derived renal volume. EBCT-determined flow correlated well with EMF measurements regardless of the algorithm used. An algorithm using the area under the time-density curve was concluded to be the most suitable for calculation of renal blood flow; it correlated with EMF as EBCT flow = 44.5 + 1.05 EMF (r = 0.885, SEE = 31.2 mL/min, P < .0001). Consistent overestimation of flow by EBCT resulted probably from retention of contrast media in the renal parenchyma. EMF showed an increase of 20 +/- 10% in renal blood flow after vasodilation. EBCT-derived global, cortical, and medullary flows increased by 33.8 +/- 10.3%, 24.8 +/- 17.8%, and 99.0 +/- 73.8%, respectively. In conclusion, EBCT was found feasible for credible quantitation of renal blood flow in the physiologic range studied.

Algorithms↗

Analysis of heartbeat dynamics by point process adaptive filtering.

Heartbeats are a point process yet, most of the current analysis methods do not model this important characteristic of these data. We describe human heartbeat time series as a history dependent inverse Gaussian model. We present a point process adaptive filter algorithm to estimate the model's time-varying parameters, and use it to compute new measures of heart rate variability. We apply our algorithm to analyze simulated heartbeat data and actual heartbeat data from a tilt table experiment and from healthy subjects and subjects with congestive heart failure during sleep. Our results suggest a new approach for characterizing heartbeat dynamics.

Algorithms↗

Soft learning vector quantization and clustering algorithms based on non-Euclidean norms: single-norm algorithms.

This paper presents the development of soft clustering and learning vector quantization (LVQ) algorithms that rely on a weighted norm to measure the distance between the feature vectors and their prototypes. The development of LVQ and clustering algorithms is based on the minimization of a reformulation function under the constraint that the generalized mean of the norm weights be constant. According to the proposed formulation, the norm weights can be computed from the data in an iterative fashion together with the prototypes. An error analysis provides some guidelines for selecting the parameter involved in the definition of the generalized mean in terms of the feature variances. The algorithms produced from this formulation are easy to implement and they are almost as fast as clustering algorithms relying on the Euclidean norm. An experimental evaluation on four data sets indicates that the proposed algorithms outperform consistently clustering algorithms relying on the Euclidean norm and they are strong competitors to non-Euclidean algorithms which are computationally more demanding.

Algorithms↗

Rate of nitric oxide production by lower alveolar airways of human lungs.

This report describes methods for measuring nitric oxide production by the lungs' lower alveolar airways (VNO), defined as those alveoli and bronchioles well perfused by the pulmonary circulation. Breath holding or vigorous rebreathing for 15-20 s minimizes removal of NO from the lower airways and results in a constant partial pressure of NO in the lower airways (PL). Then the amount of NO diffusing into the perfusing blood will be the pulmonary diffusing capacity for NO (DNO) multiplied by PL and by mass balance equals VNO, or VNO = DNO(PL). To measure PL, 10 normal subjects breath held for 20 s followed by exhalation at a constant flow rate of 0.83 +/- 0.14 (SD) l/s or rebreathed at 59 +/- 15 l/min for 20 s while NO was continuously measured at the mouth. DNO was estimated to equal five times the single-breath carbon monoxide diffusing capacity. By using breath holding, PL equaled 2.9 +/- 0.8 mmHg x 10(-6) and VNO equaled 0.39 +/- 0.12 microl/min. During rebreathing PL equaled 2.3 +/- 0.6 mmHg x 10(-6) and VNO equaled 0.29 +/- 0.11 microl/min. Measurements of NO at the mouth during rapid, constant exhalation after breath holding for 20 s or during rebreathing provide reproducible methods for measuring VNO in humans.

Adult↗

Accelerated learning by active example selection.

Much previous work on training multilayer neural networks has attempted to speed up the backpropagation algorithm using more sophisticated weight modification rules, whereby all the given training examples are used in a random or predetermined sequence. In this paper we investigate an alternative approach in which the learning proceeds on an increasing number of selected training examples, starting with a small training set. We derive a measure of criticality of examples and present an incremental learning algorithm that uses this measure to select a critical subset of given examples for solving the particular task. Our experimental results suggest that the method can significantly improve training speed and generalization performance in many real applications of neural networks. This method can be used in conjunction with other variations of gradient descent algorithms.

Algorithms↗

Comparative analysis of arterial oxygen saturations during exercise by pulse oximetry, photometric measurements, and calculation procedures.

Pulse oximetry allows non-invasive monitoring of arterial oxygen saturation (SO2). To study the validity of pulse oximetry, comparative measurements were performed. During exhaustion limited exercise SO2-values measured by pulse oximetry (SO2puls), calculated SO2-values (algorithms of Kelman, Severinghaus, and Siggaard-Andersen--SO2calc), and as "golden standard" photometric measured SO2-values (SO2meas) were compared. Fourteen triathletes performed a stepwise cycling exercise test in the supine position. SO2calc was determined on the basis of capillary actual blood gas values. SO2puls was measured continuously with a finger probe attached to the second finger. The SO2puls- and SO2calc-values differed from the SO2meas-values (p less than 0.05); however, the differences were of no clinical relevance. Performing linear regression analysis, only SO2puls correlated significantly (r = 0.47, p less than 0.001) with SO2meas. Pulse oximetry is able to replace invasive measurements of arterial oxygen saturation in athletes. It is superior to SO2-calculations and permits reliable, valid and non-invasive continuous monitoring of SO2.

Adult↗

Quantum similarity superposition algorithm (QSSA): a consistent scheme for molecular alignment and molecular similarity based on quantum chemistry.

The use of the molecular quantum similarity overlap measure for molecular alignment is investigated. A new algorithm is presented, the quantum similarity superposition algorithm (QSSA), expressing the relative positions of two molecules in terms of mutual translation in three Cartesian directions and three Euler angles. The quantum similarity overlap is then used to optimize the mutual positions of the molecules. A comparison is made with TGSA, a topogeometrical approach, and the influence of differences on molecular clustering is discussed.

Aldosterone↗

A mover-stayer model for longitudinal marker data.

Studies of chronic disease often focus on estimating prevalence and incidence in which the presence of active disease is based on dichotomizing a continuous marker variable measured with error. Examples include hypertension, asthma, and depression, where active disease is defined by setting a threshold on a continuous measure of blood pressure, respiratory function, and mood, respectively. This paper proposes a model for inference about prevalence and incidence when active disease is determined by dichotomizing a continuous marker variable in a population-based study. In this formulation, it is postulated that there are three groups of people, those that are not susceptible to the disease, those who are always in the disease state, and those who have the potential to transition between the disease and the disease-free states over time. The model is used to estimate the prevalence and incidence of the disease in the population while accounting for measurement error in the marker. An EM algorithm is used for parameter estimation and the methodology is illustrated on Framingham heart study hypertension data. A simulation study is conducted in order to demonstrate the importance of accounting for measurement error in estimating prevalence and incidence for this example.

Adult↗

Corneal thickness in glaucoma screening, diagnosis, and management.

PURPOSE OF REVIEW: Variability in central corneal thickness (CCT) is a potent confounder of most tonometry techniques, especially Goldmann applanation tonometry. The Ocular Hypertension Treatment Study (OHTS) provided important information regarding predictive factors for the eventual development of glaucoma in patients at risk of the disease. Among the most striking of the OHTS' findings was that CCT was a powerful predictor of glaucoma risk. In this review, studies subsequent to the OHTS report will be reviewed and placed in the context of what is known about CCT and its relation with tonometry and glaucoma risk. RECENT FINDINGS: Several well-designed studies have since expanded on this hypothesis, confirming that CCT bears an inverse relation with the risk of developing glaucoma damage. Other investigators have confirmed the presence of racial differences in CCT and pilot studies suggest that CCT may vary systematically in different forms of glaucoma. SUMMARY: The absence of a widely-accepted algorithm for the correction of IOP measurements should not prevent the widespread adoption of pachymetry as part of the comprehensive eye exam, as knowledge of an individual's CCT provides valuable information about their glaucoma risk.

Algorithms↗

Response force titration for the assessment of the neuromuscular toxicity of 2,5-hexanedione in rats.

A silent, non-moving glass lever combined with strain gauges and mounted in an operant chamber measured the vertical isometric force exerted by the forepaw of rats. Every weekday the rats were subjected to a force titration schedule consisting of a sequence of discrete trials signalled by a lever light. The required force, above which a water reinforcement is delivered, was regulated by a generalized bisection algorithm. A stable force level which the rat was able to attain at 50% of the trials was quickly reached in each session by this algorithm. This technique was used to measure the neuromuscular performance decrement due to repeated 2,5-hexanedione treatment (250 and 500 mg/kg/day per os). The results were compared with fore- and hindlimb grip strength measurements on the same animals. This experiment showed that the force titration technique is able to distinguish between motivational and true force decrements, a distinction which cannot be made by the grip strength technique.

Analysis of Variance↗

[Concept of the mean stopping power and the mean electron energy in electron dosimetry].

In consideration of the variations of the values E,Er,EH and Ew of the energy spectrum of electrons at the measuring point in case of a given energy on the surface Eo and in the depth t of a phantom with a low Z-number, the authors present the practical realisation of a conception allowing to determine by one single conversion curve Sw,1 (Er) the energy-dose of rapid electrons in water Dw, at least within the spectrum of Eo = 5 to 42 MeV and Er = 2.2 to 42 MeV, from the cavity ion dose Jc measured absolutely or by means of a calibrated electron chamber. Sw,1 (Er) is the relative unrestricted mass collision stopping power as a function of the mean rest energy Er at the measuring point. Er can be calculated in a simple manner from Eo and t and coincides almost perfectly with the most probable energy Ew of measured electron spectra. The authors present an algorithm for the calculation of the true mean electron energy E from Eo and t with a good coincidence with the values of measured electron spectra. It is shown that, contrary to the curve with one parameter Sw,1 (Er), a relation of Sw,1 to E leads to a series of curves with two parameters Sw,1 (Eo, t). The method using a relation of Sw,1 to Er which offers the advantage of a simple practical application and good precision is presented as "conception of the mean stopping power in electron dosimetry".

Electrons↗

An algorithmic approach to diagnosis of hypoglycemia.

An algorithm has been devised to facilitate the diagnostic approach to the causes of hypoglycemia. This systematic approach enables the physician to reach the final diagnosis in a logical way without subjecting the child to unnecessary and possibly hazardous investigations. The algorithm is based on the following measurements as required by each patient: concentrations of blood glucose, lactate, ketone bodies, and glucose-regulating hormones. These measurements are performed with the patient in the fasting state and after loading tests (glycerol and galactose) as needed. If indicated, an enzymatic test is performed to establish the final diagnosis. Eighteen children aged 1 month to 7 years who had persistent or recurrent hypoglycemia have been examined according to this algorithm. The correct diagnosis was arrived at in 17 patients. The diagnosis was not reached in one neonate who had glucose-6-phosphatase deficiency and initially did not have lactic acidosis; once lactic acidosis developed, his illness fitted perfectly into the algorithm.

Algorithms↗

A cardiac evoked response algorithm providing threshold tracking: a North American multicenter study. Clinical Investigators of the Microny-Regency Clinical Evaluation Study.

The purpose of this study was to evaluate a pacing system using the recognition of cardiac evoked response for the automatic adjustment of pacing output. Patients were prospectively followed after primary implantation of VVIR pacemakers using AutoCapture (St. Jude Medical CRMD). Sensing and pacing thresholds, polarization signal, evoked response, and AutoCapture performance were evaluated with serial visits and 24-hour Holter monitoring. Three hundred ninety-eight patients (mean age 71 +/- 15 years) were followed for an average duration of 1 year (3 days-1.75 years) with the algorithm functional in > 90% of patients. Backup pacing in the event of exit block was confirmed in all patients. Pacing thresholds remained stable at 0.89 +/- 0.34 V with a pulse width of 0.31 ms (with chronic output autoset at 0.3 V above the actual threshold). Evoked response exhibited a small but statistically significant increase with time (8.92 mV at implant, 9.60 mV at 12 months), however, this finding did not result in any change in AutoCapture function during our follow-up period. The polarization signal remained stable with minimal variation (1.12 mV at implant, 1.18 at 12 months). No clinical adverse events were observed using the AutoCapture algorithm. In this initial experience with the AutoCapture algorithm the evoked response and polarization measurements remained adequate, allowing the system to function in the majority of patients with safe, low output pacing. High energy backup pacing provided an added safety feature over fixed output devices in cases of unexpected threshold rises. Longer follow-up is required for continued long-term validation of the algorithm.

Aged↗