Abstract: The method for assessing risk of an adverse clinical event includes detecting a physiologic signal in the subject and determining from the physiologic signal a sequence of intervals corresponding to time intervals between heart beats. The long-time structure of fluctuations in the intervals over a time period of more than fifteen minutes is analyzed to assess risk of an adverse clinical event. In a preferred embodiment, the physiologic signal is an electrocardiogram and the time period is at least fifteen minutes. A preferred method for analyzing the long-time structure variability in the intervals includes computing the power spectrum and fitting the power spectrum to a power law dependence on frequency over a selected frequency range such as 10.sup.-4 to 10.sup.-2 Hz. Characteristics of the long-time structure fluctuations in the intervals is used to assess risk of an adverse clinical event.

Abstract: A multi-segment ECG electrode includes a flexible basepad, a central segment defined on a surface of the basepad, and exterior segments defined on the surface of the basepad. The exterior segments may be sized, shaped and positioned relative to the central segment so that an average position of the exterior segments approximates a position of the central segment.

Abstract: The alternans pattern of cycle-to-cycle variability in physiologic waveforms is assessed by applying transducers to a subject, recording physiologic signals, and analyzing the alternans pattern of variation in waveform morphology.

Abstract: A method of reducing noise in a signal that represents a physiologic process includes obtaining multiple input signals, measuring a relationship between noise content of the input signals, and combining the input signals in consideration of the measured relationship to produce an output signal having low noise content. The multiple input signals may include, for example, two or more primary physiologic input signals or one or more primary physiologic input signals and two or more secondary input signals that represent noise. The method may further include dividing one or more ECG input signals and secondary input signals into set of segments, where each set of segments represents a beat of the ECG signal, measuring a relationship between noise content of corresponding points from successive sets of segments, and combining the input signals based on the measured relationship.

Abstract: Method and apparatus for improved electronic display and interpretation of physiologic waveforms. The apparatus generates a two-dimensional grid on the video screen simulating the appearance of electrocardiographic recording paper or other physiologic signal recording paper. At least one physiologic signal is superimposed upon the grid for a display of the combined signal and grid. In a preferred embodiment of the invention the grid includes lines some of which are separated by no more than 2.6 millimeters. In another embodiment of the invention the grid includes horizontal or vertical lines of at least two types.

Abstract: The temporal pattern of cycle-to-cycle variability in physiologic waveforms, such as alternans, is assessed by applying transducers to a subject, recording physiologic signals, and analyzing the cycle-to-cycle variation in waveform morphology. Preferred embodiments include the application of physiologic stress to the subject in order to adjust heart rate to the desired range, real-time analysis of waveform variability, reduction in the effect of intercycle variability on waveform variability, improved techniques for determining the statistical significance of the amplitude of a temporal pattern of variability, handling of abnormal beats such as atrial and ventricular premature beats, and assessment of the statistical significance of a measured level of a temporal pattern of variability.

Abstract: An array of electrodes is applied to an internal or external surface of a biological system such as a human being. The electrodes generate signals which are processed to compute a surface differential of the surface potential at a multiplicity of spatial locations within a given time epoch. The signal processing is repeated for multiple sequential time epochs and an image is constructed from the surface differential of the surface potential for each time epoch. Thereafter, the sequential images corresponding to sequential time epochs are displayed. The two-dimensional image changes as the distribution of bioelectric sources evolves so as to provide a motion picture of electrical activity.

Abstract: The statistical properties of a biological signal intermittently obscured by a relatively independent biological process are estimated by noting the time intervals during which the obscuring process is occurring. From the time intervals, a windowing function is constructed which makes a transition from one towards zero as the process obscures the signal and a transition towards one as the process terminates. Thereafter, a statistical characterization is performed in which the windowing function is used to weight the relative contributions of corresponding segments of the biological signal. In preferred embodiments, the statistical properties include the autocorrelation function and power spectrum of biological signals such as heart rate and blood pressure.

Abstract: A method and apparatus for estimating transfer functions among multiple physiologic or biologic signals in the presence of feedback. The invention comprises the injection of broad band purturbation into one or more of the subsystems under study, and measuring signals from the subsystems. These signals are transformed to generate a new set of n signals. Casual transfer functions between the signals and additive noise sources are used to represent the relationships between the n signals. Parametric system identification techniques are then used to characterize quantitatively at least two casual transfer functions and noise sources. This method and apparatus provides a powerful tool with which to characterize the interactions of subsystems in the presence of feedback.

Abstract: Malfunctions of the cardiovascular control system may be diagnosed by examination of a patient's heart rate fluctuation power spectra. Particularly indicative of cardiovascular stress are: a level below about 0.1 (beats/min.).sup.2 in the power spectrum of heart rate fluctuations at a frequency between about 0.04 and about 0.10 Hz; a marked increase to above about 10 (beats/min.).sup.2 in a peak in the heart rate fluctuation power spectrum between about 0.04 to 0.10 Hz; and a ratio of the area under a heart rate power spectrum peak at a frequency between about 0.04 and 0.10 Hz to the area under a peak in the respiratory heart rate fluctuation power spectrum centered at the mean respiratory rate about about 0.10 Hz as having an absolute value less than 2.0 for longer than or equal to about one hour or as having an absolute value greater than about 50.

Abstract: A system for determining the cluster size distribution of submicron-size particles in a solution by optical pulse particle size analysis is provided. The system comprises a laminar flow cell having a translucent chamber, means for passing a sheath liquid and a sample liquid through the chamber, a light source and means for focusing the beam of light onto the chamber of the flow cell, a collecting lens, means for limiting collected light to a low angle, a stop, an iris, a light sensor and a means for processing the light signals. The system employs a combination of improved features which allows ultra-sensitive measurement of the cluster size distribution of particles, and can reliably detect as few as three dimers for every 10,000 monomers of micron size particles.

Abstract: This invention provides a means for determining the concentration of any of a wide range of antibody or antigen molecules with a high degree of specificity, accuracy and sensitivity. Antigen or antibody concentration is determined by effecting an agglutination reaction in a liquid medium and determining the cluster size distribution of agglutinated particles by optical pulse particle size analysis. The measured cluster size distribution then is compared with a standard quantitative relationship between the cluster size distribution and concentration of the antigen or antibody being tested. By this means one may specifically ascertain the absolute concentration of the antigen or antibody in question in the sample being analyzed. In addition to detecting antigen or antibody molecules, the process of this invention can be used to determine the concentration of any substance capable of specifically promoting or inhibiting an agglutination reaction such as viruses, white blood cells or the like.

Abstract: Myocardial electrical stability is assessed based on the derivation of an alternating ECG morphology index from a series of heartbeats. The ECG electrical signal waveform is digitized at a plurlaity of sample points for each of the series of beats. Sample point matrices from the digitized ECG signals are constructed and the alternating energy at each of the sample points for the series of beats is computed. The alternating energy over the entire set of sample points is summed to generate the total alternating energy. This total alternating energy is normalized with respect to the energy of the average waveform, the normalized value being the alternating ECG morphology index. Animal studies indicate a high negative correlation between cardiac electrical stability and the alternating ECG morphology index.

Abstract: A rapid, noninvasive technique for quantifying the dynamic response of the autonomic nervous system (ANS) to perturbations it senses over a broad range of physiologically relevant frequencies. The technique involves two steps. First, a physiologic parameter sensed by the ANS is subjected to a broad-band perturbation as an input signal while a physiologic parameter modulated by the ANS is monitored as an output signal. Then, the transfer relation between input signal and output signal is determined. The computed transfer relation is then readily interpretable in terms of responsiveness of the various limbs of the ANS.

Abstract: Myocardial electrical stability is assessed by sampling an ECG waveform at corresponding fiducial locations for a plurality of beats and creating a scatter plot of the i.sup.th sample versus the (i- 1)th sample. A parameter .lambda. is determined which minimizes the sum of the total distances of the points of the scatter plot to an equation x(i)= 4.lambda.x(i- 1)[ 1-x(i- 1)]. The value of the parameter .lambda. is related to the electrical stability of the heart.

Abstract: A method and compositions are provided to effect optimization of methods for determining concentrations of antibodies or antigens. Particles coated with an antigen or an antibody are suspended in an aqueous medium where pH and ionic strength are controlled so that the coulomb effect and the van der Waals forces on and exerted by the particles are balanced.

Abstract: A colored, positive-acting, radiation-sensitive composition whose color is extinguished or greatly decreased in intensity upon irradiation comprising at least one acid-free resin, at least one acid-sensitive dyestuff and at least one positive-acting component which yields an acidic product upon irradiation; positive-acting elements comprising suitable support materials at least one surface of which has been coated with the above composition and lithographic printing plates comprising the above elements, wherein the support materials are lithographically suitable support materials, which have been imagewise exposed to radiation wherein there is a high contrast, before development, between the colored image areas and less intensely colored or colorless non-image areas, the image areas of said plates being additionally highly stable against aqueous alkaline developers after development to remove the exposed non-image areas of the composition and more highly colored than the non-image areas of the revealed substr

Abstract: Method and apparatus for determining the concentration of any of a wide range of antigen or antibody molecules with a high degree of specificity, accuracy and sensitivity. Antigen or antibody concentration is determined by effecting an agglutination reaction between carrier particles in a liquid medium, exposing the liquid medium to a beam of light, and measuring the ratio of the intensities of light scattered at two different angles as a function of antigen or antibody concentration. The unknown concentration of antibody or antigen is determined by comparison with similar measurements of the anisotropy ratio using known concentrations of the molecule being tested for. The agglutination reaction is performed using carrier particles coated with an agglutinant. The carrier particles should be fairly uniform in size and their diameter can be less than or comparable to the wavelength of light.

Abstract: A method and compositions are provided to effect optimization of methods for determining concentrations of antibodies or antigens. Particles coated with an antigen or an antibody are suspended in an aqueous medium where pH and ionic strength are controlled so that the coulomb effect and the van der Waals forces on and exerted by the particles are balanced.

Abstract: This inventin provides a means for determining the concentration of any of a wide range of antibody or antigen molecules with a high degree of specificity, accuracy and sensitivity. Antigen or antibody concentration is determined by effecting an agglutination reaction in a liquid medium and determining the mean diffusion constant of the agglutinated reaction product by quasi-elastic light scattering spectroscopy. The measured mean diffusion constant then is compared with a standard quantitative relationship between mean diffusion constant and concentration of the antigen or antibody being tested. By this means one may specifically ascertain the absolute concentration of the antigen or antibody in question in the sample being analyzed. In addition to detecting antigen or antibody molecules, the process of this invention can be used to determine the concentration of any substance capable of specifically promoting or inhibiting an agglutination reaction such as viruses, white blood cells or the like.