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PubMedDate not supplied

Nonlinear systems theory in medical care management.

Health care is provided to biological, not mechanical systems. The focus of attention is a human being, not an automobile or clock. Biological systems are highly complex and their behavior can be nonlinear. By understanding this difference, we can begin to answer the question of how can we deliver efficient and effective clinical care, while controlling spiraling costs. This article describes the behavior of complex systems and explores what has been learned about managing such systems in non health care fields. The author translates that learning into the health care setting and proposes a new model for the health care environment, based on the principles of complex adaptive systems. The approach advocated is to design models that can learn and adapt, and then to implement them with skill. Such models should include the elements of roadmaps, decision aids, and continuous improvement.

Decision Making, Organizational↗

PubMedDate not supplied

Stability of heartbeat interval distributions in chronic high altitude hypoxia.

Recent studies of nonlinear dynamics of the long-term variability of heart rate have identified nontrivial long-range correlations and scale-invariant power-law characteristics (l/f noise) that were remarkably consistent between individuals and were unrelated to external or environmental stimuli (Meyer et al., 1998a). The present analysis of complex nonstationary heartbeat patterns is based on the sequential application of the wavelet transform for elimination of local polynomial nonstationary behavior and an analytic signal approach by use of the Hilbert transform (Cumulative Variation Amplitude Analysis). The effects of chronic high altitude hypoxia on the distributions and scaling functions of cardiac intervals over 24 hr epochs and 4 hr day/nighttime subepochs were determined from serial heartbeat interval time series of digitized 24 hr ambulatory ECGs recorded in 9 healthy subjects (mean age 34 yrs) at sea level and during a sojourn at high altitude (5,050 m) for 34 days (Ev-K2-CNR Pyramid Laboratory, Sagarmatha National Park, Nepal). The results suggest that there exists a hidden, potentially universal, common structure in the heterogeneous time series. A common scaling function with a stable Gamma distribution defines the probability density of the amplitudes of the fluctuations in the heartbeat interval time series of individual subjects. The appropriately rescaled distributions of normal subjects at sea level demonstrated stable Gamma scaling consistent with a single scaled plot (data collapse). Longitudinal assessment of the rescaled distributions of the 24 hr recordings of individual subjects showed that the stability of the distributions was unaffected by the subject's exposure to a hypobaric (hypoxic) environment. The rescaled distributions of 4 hr subepochs showed similar scaling behavior with a stable Gamma distribution indicating that the common structure was unequivocally applicable to both day and night phases and, furthermore, did not undergo systematic changes in response to high altitude. In contrast, a single function stable over a wide range of time scales was not observed in patients with congestive heart failure or patients after cardiac transplantation. The functional form of the scaling in normal subjects would seem to be attributable to the underlying nonlinear dynamics of cardiac control. The results suggest that the observed Gamma scaling of the distributions in healthy subjects constitutes an intrinsic dynamical property of normal heart function that would not undergo early readjustment or late acclimatization to extrinsic environmental physiological stress, e.g., chronic hypoxia.

Acclimatization↗

PubMed1999

Photopic and scotopic light detection in patients with seasonal affective disorder and control subjects.

BACKGROUND: Retinal sensitivity may play a role in the pathogenesis of seasonal affective disorder (SAD) and response to light therapy. METHODS: Using a dark adaptation procedure, SAD patients and normal control subjects were tested in the winter and summer, with patients retested after light treatment. The eyes were preadapted to bright light followed by 30 min in darkness, during which subjects detected a dim signal titrated around the detection threshold. Photopic (cone-mediated) and scotopic (rod-mediated) components of the data were identified by nonlinear exponential curve fits to successive threshold estimates. RESULTS: Patients (n = 24) showed significantly lower cone and rod thresholds in the summer than winter, while control subjects (n = 12) showed a similar trend. Relative to the control subjects, however, patients were supersensitive in winter (lower cone final threshold, faster rod recovery). Clinical responders to morning light showed a small summer-like increase in cone sensitivity, whereas nonresponders became subsensitive. In comparison to darker-eyed patients, blue-eyed patients showed a larger summertime increase in cone sensitivity and a similar trend after response to morning light. CONCLUSIONS: Heightened retinal sensitivity with increased light exposure, and supersensitivity of patients relative to control subjects in winter, may play roles in the pathogenesis of winter depression and the action of therapeutic light.

Adolescent↗

PubMed2002

Resilience and sustainable development: building adaptive capacity in a world of transformations.

Emerging recognition of two fundamental errors underpinning past polices for natural resource issues heralds awareness of the need for a worldwide fundamental change in thinking and in practice of environmental management. The first error has been an implicit assumption that ecosystem responses to human use are linear, predictable and controllable. The second has been an assumption that human and natural systems can be treated independently. However, evidence that has been accumulating in diverse regions all over the world suggests that natural and social systems behave in nonlinear ways, exhibit marked thresholds in their dynamics, and that social-ecological systems act as strongly coupled, complex and evolving integrated systems. This article is a summary of a report prepared on behalf of the Environmental Advisory Council to the Swedish Government, as input to the process of the World Summit on Sustainable Development (WSSD) in Johannesburg, South Africa in 26 August 4 September 2002. We use the concept of resilience--the capacity to buffer change, learn and develop--as a framework for understanding how to sustain and enhance adaptive capacity in a complex world of rapid transformations. Two useful tools for resilience-building in social-ecological systems are structured scenarios and active adaptive management. These tools require and facilitate a social context with flexible and open institutions and multi-level governance systems that allow for learning and increase adaptive capacity without foreclosing future development options.

Agriculture↗

PubMed1983

A systems model for the pupil size effect. I. Transient data.

The human pupillary control system is a paradigm for linearized biological control systems. It also exhibits a series of interesting nonlinear behaviors, particularly asymmetry, "pupillary escape," and "pupillary capture." We present a nonlinear model in which a signal dependent upon pupil size is fed back internally to cause a change in system parameters related to gains and rates of light adaptation. The model was simulated on a digital computer, a variety of experimental data was well matched, and improvements over previous pupil models demonstrated. A candidate physiological mechanism for adaptive components of the model might have the form of an inverse "Henneman coded" neuronal pool.

Animals↗

PubMedDate not supplied

A controller for automatic regulation of induced paralysis during surgery.

This paper presents a strategy for automatic control of induced paralysis using vecuronium bromide during surgery. The controller is self-tuning and adapts to inter-patient and intra-patient response variations while optimizing the output variance and infusion rate. In particular, the controller is capable of accommodating the variations of pure time delays in patient response. The performance of the controller is evaluated using an experimentally derived pharmacokinetic and nonlinear pharmacodynamic model of patient response. The results indicate that the controller provides robust regulation of the paralysis level with no output offset.

Algorithms↗

PubMed2005

The numerical simulation of osteophyte formation on the edge of the vertebral body using quantitative bone remodeling theory.

OBJECTIVES: To extend the quantitative prediction of the external shape of bone structure to the simulation of osteophyte formation on the edge of vertebral body. METHODS: The high-order nonlinear equation of bone remodeling was used to control osteophyte formation process. The idea of topology optimization in engineering was imported to allow the outgrowth of osteophyte. Osteophyte on the edge of a vertebral body in its mid-sagittal plane was simulated numerically. RESULTS: Osteophyte formation is an adaptive bone remodeling process in response to the progressive changes of mechanical environment, which were mainly caused by intervertebral disc degeneration. CONCLUSION: The numerical simulation in this paper extended the structural simulation based on the quantitative bone remodeling theory to bone morphological abnormity in orthopaedics, which can help to better understand the relationship between bone morphological abnormity and the mechanical environment.

Bone Density↗

PubMed2001

Non-linear development of postural control and strategy use in young children: a longitudinal study.

This longitudinal analysis confirmed a non-monotonic pattern of postural control development in children from age 5 to 8 years suggested by previous cross-sectional studies. Postural control was considered in terms of control strategy and its variability operationalized by mean and standard deviation of center of pressure (COP) velocity; and of effectiveness and its variability operationalized by mean and standard deviation of COP anteroposterior (a-p) excursion. Periods of significant variability were used to indicate behavioral transitions. Seventeen healthy children (nine males, eight females) aged 5-6 years (61.5-75 months) were tested at 3- to 4-month intervals up to age 8 years (83-97 months) in eyes-open quiet stance on a force platform for 30 s in each of ten trials. Data were reorganized into six developmental categories based on adjacent test dates prior to (-1) and after (+1, +2, +3, +4) a subject's trial with the lowest COP velocity (0). Developmental category is proposed to represent level of sensorimotor integrative skill. Within-subject ANCOVAs revealed a significant effect (P<0.0001) for developmental category with covariance due to height, weight and actual age removed. Post hoc tests showed a significant effect (P<0.0001) on measures of strategy. However, differences in COP velocity (type of strategy used) and differences in its variability (denoting a transition between strategies) were not always coincident. Performance outcome (COP a-p excursion) changed near linearly across categories. It was concluded that a non-monotonic change in control strategy as indicated by COP velocity describes the development of quiet stance equilibrium. A transition occurs from a primarily open-loop to incorporation of open- and closed-loop components of control. Honing of strategy used precedes and follows transitions. Constriction of velocity and excursion may typify the early stages of bimodal strategy. Developmental categories describe affiliation with the strategy employed and may represent differentiable levels of sensorimotor integrative skill. They may be more useful in assessing progression of equilibrium control than consecutive age in years.

Adaptation, Physiological↗

PubMed1984

Mechanical loading histories and cortical bone remodeling.

A conceptual framework is presented for understanding and investigating structural adaptation of cortical bone. The magnitudes, orientations, and sense (tension or compression) of the physiologically incurred cyclic principal strains vary markedly throughout the skeleton. It is probable, therefore, that the strain/remodeling response of bone is site specific. Furthermore, there is some indication that immature bone is more responsive to alterations of cyclic strains than mature bone. Animal experimental studies and complementary stress and strain analyses suggest that the structural adaptation due to changes in cyclic strain fields may be a very nonlinear response. Bone loss in mature animals due to immobilization is sensitive to even small changes in the cyclic bone strains. Under normal conditions, however, there appears to be a broad range of physical activity in which bone is relatively unresponsive to changes in loading history. With severe repeated loading, bone hypertrophy can be pronounced. These observations open the possibility that bone atrophy and hypertrophy are controlled by different mechanisms. Therefore, two (or more) complementary control systems may be involved in the regulation of bone mass by bone cyclic strain histories. It is probable that bone mechanical microdamage is one control stimulus for affecting an increase in bone mass.

Adaptation, Physiological↗

PubMed2003

Learning the nonlinearity of neurons from natural visual stimuli.

Learning in neural networks is usually applied to parameters related to linear kernels and keeps the nonlinearity of the model fixed. Thus, for successful models, properties and parameters of the nonlinearity have to be specified using a priori knowledge, which often is missing. Here, we investigate adapting the nonlinearity simultaneously with the linear kernel. We use natural visual stimuli for training a simple model of the visual system. Many of the neurons converge to an energy detector matching existing models of complex cells. The overall distribution of the parameter describing the nonlinearity well matches recent physiological results. Controls with randomly shuffled natural stimuli and pink noise demonstrate that the match of simulation and experimental results depends on the higher-order statistical properties of natural stimuli.

Models, Neurological↗

PubMed2004

Steepest descent with momentum for quadratic functions is a version of the conjugate gradient method.

It is pointed out that the so called momentum method, much used in the neural network literature as an acceleration of the backpropagation method, is a stationary version of the conjugate gradient method. Connections with the continuous optimization method known as heavy ball with friction are also made. In both cases, adaptive (dynamic) choices of the so called learning rate and momentum parameters are obtained using a control Liapunov function analysis of the system.

Algorithms↗

PubMed2005

Generalization of motor learning based on multiple field exposures and local adaptation.

Previous studies have used transfer of learning over workspace locations as a means to determine whether subjects code information about dynamics in extrinsic or intrinsic coordinates. Transfer has been observed when the torque associated with joint displacement is similar between workspace locations-rather than when the mapping between hand displacement and force is preserved-which is consistent with muscle- or joint-based encoding. In the present study, we address the generality of an intrinsic coding of dynamics and examine how generalization occurs when the pattern of torques varies over the workspace. In two initial experiments, we examined transfer of learning when the direction of a force field was fixed relative to an external frame of reference. While there were no beneficial effects of transfer after training at a single location (experiments 1 and 2), excellent performance was observed at the center of the workspace after training at two lateral locations (experiment 2). Experiment 3 and associated simulations assessed the characteristics of this generalization. In these studies, we examined the patterns of transfer observed after adaptation to force fields that were composed of two subfields that acted in opposite directions. The experimental and simulated data are consistent with the idea that information about dynamics is encoded in intrinsic coordinates. The nervous system generalizes dynamics learning by interpolating between sets of control signals, each locally adapted to different patterns of torques.

Adaptation, Physiological↗

PubMed1982

A heuristic mathematical model for the dynamics of sensory conflict and motion sickness.

The etiology of motion sickness is now usually explained in terms of a qualitatively formulated "sensory conflict" hypothesis. By consideration of the information processing task faced by the central nervous system in estimating body spatial orientation and in controlling active body movement using an "internal model" referenced control strategy, a mathematical model for sensory conflict generation is developed. The model incorporates and extends models proposed by von Holst, Held, and Reason, and is congruent with multisensory models for spatial orientation developed by Young and coworkers. The model postulates a major dynamic functional role for sensory conflict signals in movement control, as well as in sensory-motor adaptation. It accounts for the role of active movement in creating motion sickness symptoms in some experimental circumstances, and in alleviating them in others. The relationship between motion sickness produced by "sensory rearrangement" and that resulting from external motion disturbances is explicitly defined. A nonlinear conflict averaging model is proposed which describes dynamic aspects of experimentally observed subjective discomfort sensation, and suggests resulting behaviours. The model admits several possibilities for adaptive mechanisms which do not involve internal model updating. Further systematic efforts to experimentally refine and validate the model are indicated.

Conflict, Psychological↗

PubMed2004

Dynamical resetting of the human brain at epileptic seizures: application of nonlinear dynamics and global optimization techniques.

Epileptic seizures occur intermittently as a result of complex dynamical interactions among many regions of the brain. By applying signal processing techniques from the theory of nonlinear dynamics and global optimization to the analysis of long-term (3.6 to 12 days) continuous multichannel electroencephalographic recordings from four epileptic patients, we present evidence that epileptic seizures appear to serve as dynamical resetting mechanisms of the brain, that is the dynamically entrained brain areas before seizures disentrain faster and more frequently (p < 0.05) at epileptic seizures than any other periods. We expect these results to shed light into the mechanisms of epileptogenesis, seizure intervention and control, as well as into investigations of intermittent spatiotemporal state transitions in other complex biological and physical systems.

Adaptation, Physiological↗

PubMed1982

Adaptation in auditory-nerve fibers: a revised model.

Adaptation of firing rates in auditory-nerve fibers appears to reflect two distinct processes. Rapid adaptation occupies the first few milliseconds of response and is superimposed upon short-term adaptation which has a time constant of about 40 ms. The properties of the two processes are reviewed and compared, and a phenomenological model is developed that successfully accounts for them. The model consists of several stages which have been tentatively associated with underlying physiological processes. In the first stage stimulus intensity is transformed by a static nonlinearity, followed by a low-pass filter. The filtered output may correspond to the hair-cell receptor potential. It modulates the release of a substance that possibly represents synaptic transmitter. Adaptation is produced by the depletion of transmitter which is located in three stores in cascade. A global store with fixed concentration controls the steady-state response and replenishes a local store which is responsible for short-term adaptation. The local store replenishes a rapidly depleted immediate store. Flow between stores is proportional to concentration gradients with the following exceptions. The immediate store is subdivided into independent volumes or sites and there is no flow among sites or back to the local store. A given site becomes activated only when the receptor potential exceeds its particular activation value and the number of activated sites is proportional to the receptor potential. The flow of transmitter from the immediate store is assumed to be proportional to neural firing rate, with some minor modifications described in the text. The properties of the model are determined from the underlying equations and from a computer simulation. The model produces realistic response properties including PST histograms, onset and steady-state rate-intensity functions, incremental and decremental responses, response modulation for amplitude modulated stimuli, and period histograms for low-frequency tones.

Acclimatization↗

PubMed1999

Effect of aerobic training on orthostatic tolerance, circulatory response, and heart rate dynamics.

BACKGROUND: This study was performed to investigate the effects of aerobic training on orthostatic tolerance and to quantify the post-training changes in cardiovascular response and heart rate variability (HRV). METHODS: Tolerance and circulatory responses to two types of lower body negative pressure (LBNP) were examined and compared in a group of healthy male students before and after 6 mo of aerobic training, and the results were further compared with a group of athletes (runners). Changes in HRV associated with training were analyzed by conventional and time-varying autoregressive spectral analysis, as well as by approximate entropy measurement (ApEn)--a statistic quantifying heart rate "complexity" derived from non-linear dynamics. RESULTS: After aerobic training, there was an initial transient hypotension during the supine -50 mmHg LBNP testing and a significant decrease in tolerance to upright graded LBNP in most of the student-subjects. Moreover, after training, there was a significant decrease in ApEn value of the HRV time series during both supine control and LBNP testing, and the rate of cardiac vagal withdrawal and sympathetic activation during the onset of LBNP was faster than that before training. CONCLUSIONS: The present study has provided further evidence that certain types of aerobic training may affect orthostatic tolerance and may be associated with a loss of complexity of HRV during supine resting and orthostatic stress.

Adaptation, Physiological↗

PubMed2005

Machine learning approaches for phenotype-genotype mapping: predicting heterozygous mutations in the CYP21B gene from steroid profiles.

OBJECTIVE: Non-linear relations between multiple biochemical parameters are the basis for the diagnosis of many diseases. Traditional linear analytical methods are not reliable predictors. Novel nonlinear techniques are increasingly used to improve the diagnostic accuracy of automated data interpretation. This has been exemplified in particular for the classification and diagnostic prediction of cancers based on expression profiling data. Our objective was to predict the genotype from complex biochemical data by comparing the performance of experienced clinicians to traditional linear analysis, and to novel non-linear analytical methods. DESIGN AND METHODS: As a model, we used a well-defined set of interconnected data consisting of unstimulated serum levels of steroid intermediates assessed in 54 subjects heterozygous for a mutation of the 21-hydroxylase gene (CYP21B) and in 43 healthy controls. RESULTS: The genetic alteration was predicted from the pattern of steroid levels with an accuracy of 39% by clinicians and of 64% by linear analysis. In contrast, non-linear analysis, such as self-organizing artificial neural networks, support vector machines, and nearest neighbour classifiers, allowed for higher accuracy up to 83%. CONCLUSIONS: The successful application of these non-linear adaptive methods to capture specific biochemical problems may have generalized implications for biochemical testing in many areas. Nonlinear analytical techniques such as neural networks, support vector machines, and nearest neighbour classifiers may serve as an important adjunct to the decision process of a human investigator not 'trained' in a specific complex clinical or laboratory setting and may aid them to classify the problem more directly.

Adult↗

PubMed1995

Very fast simulated reannealing in radiation therapy treatment plan optimization.

PURPOSE: Very Fast Simulated Reannealing is a relatively new (1989) and sophisticated algorithm for simulated annealing applications. It offers the advantages of annealing methods while requiring shorter execution times. The purpose of this investigation was to adapt Very Fast Simulated Reannealing to conformal treatment planning optimization. METHODS AND MATERIALS: We used Very Fast Simulated Reannealing to optimize treatments for three clinical cases with two different cost functions. The first cost function was linear (minimum target dose) with nonlinear dose-volume normal tissue constraints. The second cost function (probability of uncomplicated local control) was a weighted product of normal tissue complication probabilities and the tumor control probability. RESULTS: For the cost functions used in this study, the Very Fast Simulated Reannealing algorithm achieved results within 5-10% of the final solution (100,000 iterations) after 1000 iterations and within 3-5% of the final solution after 5000-10000 iterations. These solutions were superior to those produced by a conventional treatment plan based on an analysis of the resulting dose-volume histograms. However, this technique is a stochastic method and results vary in a statistical manner. Successive solutions may differ by up to 10%. CONCLUSION: Very Fast Simulated Reannealing, with modifications, is suitable for radiation therapy treatment planning optimization. It produced results within 3-10% of the optimal solution, produced using another optimization algorithm (Mixed Integer Programming), in clinically useful execution times.

Algorithms↗