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PubMed2004

Response of the osteocyte syncytium adjacent to and distant from linear microcracks during adaptation to cyclic fatigue loading.

Cyclic loading induces fatigue in bone and initiates a complex, functionally adaptive response. We investigated the effect of a single period of fatigue on the histologic structure and biomechanical properties of bone. The ulnae of 40 rats were subjected to cyclic fatigue (-6000 microepsilon) unilaterally until 40% loss of stiffness developed, followed by 14 days of adaptation. The contralateral ulna served as a treatment control (n = 20 rats), and a baseline loaded/non-loaded group (n = 20 rats/group) was included. Bones from 10 rats/group were examined histologically and the remaining bones (10 rats/group) were tested mechanically. The following measurements were collected: volumetric bone mineral density (vBMD); ultimate force (Fu); stiffness (S); energy-to-failure (U); cortical area (Ct.Ar); microcrack density (Cr.Dn); microcrack mean length (Cr.Le); microcrack surface density (Cr.S.Dn); osteocyte density (Ot.N/T.Ar and Ot.N/TV); bone volume fraction (B.Ar/T.Ar); resorption space density (Rs.N/Ct.Ar); and maximum and minimum area moments of inertia (IMAX and IMIN). Using confocal microscopy, the bones were examined for diffuse matrix injury, canalicular disruption, and osteocyte disruption. The adapted bones had increased B.Ar, IMAX, and IMIN in the mid-diaphysis. Fatigue loading decreased structural properties and induced linear microcracking. At 14 days, adaptation restored structural properties and microcracking was partially repaired. There was a significant nonlinear relationship between Ot.N/T.Ar and B.Ar/T.Ar during adaptation. Disruption of osteocytes was observed adjacent to microcracks immediately after fatigue loading, and this did not change after the period of adaptation. In fatigue-loaded bone distant from microcracks, diffuse matrix injury and canalicular disruption were often co-localized and were increased in the lateral (tension) cortex. These changes were partially reversed after adaptation. Loss of canalicular staining and the presence of blind-ends in regions with matrix injury were suggestive of rupture of dendritic cell processes. Taken together, these data support the general hypothesis that the osteocyte syncytium can respond to cyclic loading and influence targeted remodeling during functional adaptation. Changes in the appearance of the osteocyte syncytium were found in fatigue-loaded bone with and without linear microcracks. We hypothesize that the number of dendritic cell processes that experience load-related disruption may determine osteocyte metabolic responses to loading and influence targeted remodeling.

Adaptation, Physiological↗
PubMed2004

Indicial response functions of growth and remodeling of common bile duct postobstruction.

Biliary duct obstruction is an important clinical condition that stems from cholelithiasis, the neoplasm in the wall or, most commonly, gallbladder stones. The objective of this study is to understand the structural and mechanical remodeling of the common bile duct (CBD) postobstruction. Porcine CBD was ligated near the duodenum that increased the duct's pressure from 6.4 to 18.3 cmH(2)O in the first 12 h and to 30.7 cmH(2)O after 32 days. The remodeling process was studied after 3 h, 12 h, 2 days, 8 days, and 32 days (n = 5 in each group) after obstruction. One additional animal in each group was sham operated. At each scheduled time, the time course of change of morphometry (diameter, length, wall thickness, etc.) and mechanical properties (stress, strain, etc.) was documented. It was found that the diameter increased by about threefold and the wall thickness of the CBD doubled in the 32-day group compared with the sham group (P < 0.001). The stress and strain increased initially with increase in pressure but recovered to near the control values by day 32 due to the structural and mechanical adaptations. Hence, the net effect of the structural and mechanical remodeling is to restore the stress and strain to their homeostatic values. Furthermore, the strain recovers more rapidly and more completely than stress. Finally, the remodeling data were expressed mathematically in terms of indicial response functions (IRF), i.e., change of a particular feature of a CBD in response to a unit step change of the pressure. The IRF approach provides a quantitative description of the remodeling process in the CBD.

Algorithms↗
PubMed2002

Comparative analysis of locally adaptive image enhancement for 3D ultrasound images.

In this article we compare methods for locally adaptive preprocessing of 3D ultrasound (US) images and their different capabilities of enhancing diagnostically important anatomical structures. We show that suitability and optimization of methods depend on the objective of the preprocessing task, e.g., slice representation or volume rendering. This article analyzes which features should be used to control the enhancement algorithm For slice representations optimization of local statistics is appropriate to maintain diagnostically important structures. Features with good region separation properties are preferable for volume rendering tasks. We demonstrate our results with US images from clinical examinations.

Algorithms↗
PubMed1997

Role of personality self-organization in development of mental order and disorder.

Normal and abnormal personality development can be quantified in terms of 15 specific steps in the self-organization of character as a complex adaptive system. Character is measured as three dimensions of Self-directedness, Cooperativeness, and Self-transcendence, each with five components corresponding to steps in personality development. Each of these steps is differentially influenced by heritable temperament dimensions, antecedent steps in character development, and life experiences. Predictions about the nonlinear dynamics of personality development, such as equifinality and multifinality, are confirmed in longitudinal data about individuals representative of the general population. The stepwise development of character determines large differences between individuals in their risk of psychopathology, as well as varying degrees of maturity and health.

Child↗
PubMed2005

Biomechanical impact of aluminum accumulation on the pre- and post-yield behavior of rat cortical bone.

In order to analyze the effects on whole-bone behavior of aluminum accumulation, 14 rats, aged 90 days, received i.p. doses of 27 mg/day of elemental Al, as Al(OH)3, during 26 weeks, while 14 rats remained as controls. Their femur diaphyses were studied tomographically by peripheral quantitative computed tomography (pQCT) and mechanically tested in bending. The load/deformation curves obtained allowed distinction between effects observed during the linearly elastic (Hookean) and nonlinear (non-Hookean, or plastic) behaviors of bones before and after the yield point, respectively. Treatment reduced the cortical bone mineralization (volumetric bone mineral density [BMD], -2%; P < 0.01), with a negative impact on the bending stiffness (Young's elastic modulus) and the yield stress of cortical bone (-18% and -13%; P < 0.05). Despite the absence of any cortical mass increase (cross-sectional area), improved spatial distribution of cortical tissue concerning anterior-posterior bending stress (cross-sectional moment of inertia, 10%; P < 0.05) occurred through a modulation of modeling drifts. Up to the yield point, neither the structural strength (load supported), the strain, nor the structural stiffness (load/deformation ratio) of the diaphyses were affected. This suggests an adaptive response of bone geometry to the impairment of bone material stiffness. However, Al intoxication significantly reduced the ultimate load and the post-yield fraction of that load (-6% and -27%; P < 0.05). This suggests that the proposed, adaptive response could have improved bone design so as to make it adequate for maintaining a normal pre-yield diaphyseal stiffness and strength according to the bone mechanostat theory, but not so as to provide complete protection of the diaphyseal post-yield (and ultimate) strength. Although a relative inhibition of bone formation could not be discarded, an Al-induced impairment of the bone ability to resist loads beyond the yield point could have caused the unusual disparity observed between effects on bone (elastic) stiffness and (ultimate) strength. In addition, to explain the unusual finding, these results suggest that little-studied microstructural factors (spatial arrangement of elements within the mineralized tissue) affecting the post-yield behavior of cortical bone, regardless of bone mineralization in these and other conditions, ought to be further investigated in specifically designed studies as a novel, promising resource in skeletal research.

Aluminum↗
PubMed2005

Dynamics of task sets: evidence from dense-array event-related potentials.

Prior research suggests that task sets facilitate coherent, goal-directed behavior by providing an internal, contextual frame that biases selection toward context-relevant stimulus attributes and responses. Questions about how task sets are engaged, maintained, and shifted have recently become a major focus of research on executive control processes. We employed dense-array (128-channel) event-related potential (ERP) methodology to examine the dynamics of brain systems engaged during the preparation and implementation of task switching. The EEG was recorded while participants performed letter and digit judgments to pseudorandomly-ordered, univalent (#3, A%) and bivalent (G5) stimulus trials, with the appropriate task cued by a colored rectangle presented 450 ms before target onset. Results revealed spatial and temporal variations in brain activity that could be related to preparatory processes common to both switch and repeat trials, switch-specific control processes engaged to reconfigure and maintain task set under conflict, and visual priming benefits of task repetition. Despite extensive practice and improvement, both behavioral and ERP results indicated that subjects maintained high levels of executive control processing with extended task engagement. The patterns of ERP activity obtained in the present study fit well with functional neuroanatomical models of self-regulation of action. The frontopolar and right-lateralized frontal switch effects obtained in the present study are consistent with the role of these regions in adapting to changing contextual contingencies. In contrast, the centroparietal P3b and N384 effects related to the contextual ambiguity of bivalent trials are consistent with the context monitoring and updating functions associated with the posterior cingulate learning circuit.

Adolescent↗
PubMedDate not supplied

Culture in chaos: the need for leadership and followership in medicine.

The health care industry is changing at a dizzying pace and most of its players are struggling to maintain some form of the status quo. But resisting change will not prove fruitful--ultimately, it will rob physician executives of the opportunity to be architects in designing a new, more efficient health care system and their role in it. Because health care is a complex adaptive system (CAS)--change occurs rapidly and events are unpredictable--the old command and control style of leadership and a linear way of interpreting events is too rigid and, therefore, an ineffective model for guiding change. Complexity science offers insights about leading for change. In CASs, changes emerge in response to environmental demands for adaptability. Since the nature of these demands is unpredictable, the role of leadership is to manage the relationships and context out of which these changes emerge. A leadership style is called for that leads to purpose, makes positive changes by influencing context and relationships, and takes followers to a better place.

Adaptation, Psychological↗
PubMed2006

The benefits of standardized nursing languages in complex adaptive systems such as hospitals.

Paperwork is a major source of frustration for hospital nurses and takes valuable time away from patient care. Studies indicate that nurses spend an estimated 13% to 28% of total shift time documenting. The growth in documentation requirements for nurses can, in part, be attributed to an exponential rise in health system complexity. Authors explore the documentation of nursing care plans from a complex adaptive system perspective and then analyze the utility of adopting a standardized nursing language. An actual case history of a nursing unit's attempt to reduce complexity, improve completion time, and increase staff satisfaction in care planning by adopting a standardized nursing language is provided to emphasize a practical application.

Coronary Care Units↗
PubMed2002

Statistical procedures to test for linearity and estimate threshold doses for tumor induction with nonlinear dose-response relationships in bioassays for carcinogenicity.

Sublinear shapes of the dose-response curve in the low-dose range of toxicity testing are often postulated to be indicative of a no-effect threshold. We present statistical procedures to test sublinear dose responses in bioassays for carcinogenicity against the hypothesis of linearity and estimate a lower confidence limit for the dose at the postulated breakpoint. First, a control tumor incidence of 0 is assumed. Tumor incidence at dose 1 is allowed to range from 0 to 4 tumor-bearing animals (TBAs) in groups of 50 animals, dose 2 is assumed to result in a tumor incidence of 5-25 TBAs. The null hypothesis of a linear dose response is tested by (i) the likelihood ratio (LR) test and (ii) the minimum chi(2) (MC) method. Validation by simulation showed the MC method to be more conservative than the LR test. At the 5% level with MC, the following observed numbers of TBAs for the dose sequence 0-1-2 resulted in rejection of the hypothesis of linearity: 0-0-6, 0-1-10, 0-2-13, 0-3-16, 0-4-18. Second, the analysis was adapted to allow for a control tumor incidence of 0-4 TBAs/50 and a tumor incidence of 0-10 TBAs/50 at dose 1, and the minimum number of TBAs at dose 2 to reject linearity at the 5% level was calculated. Third, a program is made available to analyze data derived from protocols that include nonstandard dose span and group size. Internet access to the respective statistics software and source file is provided. Examples for nasal tumor induction by formaldehyde and for the induction of renal adenocarcinoma by ochratoxin A are shown. The proposed analysis may be useful to test sublinear sections of the dose response for the possibility of a threshold for carcinogens and to define dose levels that could be used as a starting point for setting exposure standards.

Adenocarcinoma↗
PubMed2004

Complex dynamics in simple systems with periodic parameter oscillations.

We study systems with periodically oscillating parameters that can give way to complex periodic or nonperiodic orbits. Performing the long time limit, we can define ergodic averages such as Lyapunov exponents, where a negative maximal Lyapunov exponent corresponds to a stable periodic orbit. By this, extremely complicated periodic orbits composed of contracting and expanding phases appear in a natural way. Employing the technique of epsilon-uncertain points, we find that values of the control parameters supporting such periodic motion are densely embedded in a set of values for which the motion is chaotic. When a tiny amount of noise is coupled to the system, dynamics with positive and with negative nontrivial Lyapunov exponents are indistinguishable. We discuss two physical systems, an oscillatory flow inside a duct and a dripping faucet with variable water supply, where such a mechanism seems to be responsible for a complicated alternation of laminar and turbulent phases.

Adaptation, Physiological↗
PubMed1996

Logarithmic time course of sensory adaptation in electrosensory afferent nerve fibers in a weakly electric fish.

1. We recorded single unit activity from individual primary electrosensory afferent axons in the posterior branch of the anterior lateral line nerve of gymnotid weakly electric fish, Apteronotus leptorhynchus. We analyzed the responses of P-type (probability-coding) afferent fibers to externally applied amplitude step changes in the quasi-sinusoidal transdermal potential established by the fish's own electric organ discharge (EOD). 2. In response to AM step increases in transdermal potential, the firing rate of P-type afferents exhibited an abrupt increase followed by an initially rapid and subsequently more gradual decay back toward the baseline level. Afferent responses continued to adapt slowly throughout the duration of prolonged step stimuli lasting > 100 s. The time course of sensory adaptation was similar for all units tested. 3. We introduce a new functional form for describing the time course of sensory adaptation in which the change in firing rate delta r decays logarithmically with time: delta r(t) = A/[B In (t) + 1]. This logarithmic form accurately describes the adaptation time course of P-type afferents over five decades in time, from milliseconds to hundreds of seconds, with only two free parameters. Using a nonlinear least-squares fitting technique, we obtained a mean value of the parameter B, which characterizes the adaptation time course, of 0.149 +/- 0.028 (mean +/- SD, n = 49). 4. We compare logarithmic fits with traditional multiexponential and power law forms and demonstrate that the logarithmic form yields a better characterization of P-type afferent responses. This analysis helps explain the variability in previously reported adaptation time constants, which have ranged from 0.2 to 3.4 s, in gymnotid P-type afferents. 5. We tested the linearity of P-type afferent responses using positive and negative AM steps of varying amplitudes. Aside from nonlinearities associated with rectification (firing rates cannot be negative) and saturation (firing rates cannot exceed the EOD frequency), we found that P-type afferent responses scaled linearly with stimulus amplitude. 6. Based on the observed linearity, we predict the frequency domain response characteristics of P-type afferents and find that the predicted gain and phase are in good agreement with experimental measurements using sinusoidal AM stimuli over a range of AM frequencies from 1 to 100 Hz. Thus the logarithmic parameterization of the step appears to accurately capture the response dynamics of P-type afferents over a wide range of behaviorally relevant AM frequencies. 7. We conclude that the temporal filtering properties of pyramidal cells in the medullary electrosensory nucleus, the electrosensory lateral line lobe (ELL), need to be reevaluated in light of the logarithmic adaptation time course in the periphery, and we discuss implications for the role of P-type afferents in driving a feedback gain control mechanism that regulated ELL pyramidal cell responsiveness.

Action Potentials↗
PubMed1998

Response regulator output in bacterial chemotaxis.

Chemotaxis responses in Escherichia coli are mediated by the phosphorylated response-regulator protein P-CheY. Biochemical and genetic studies have established the mechanisms by which the various components of the chemotaxis system, the membrane receptors and Che proteins function to modulate levels of CheY phosphorylation. Detailed models have been formulated to explain chemotaxis sensing in quantitative terms; however, the models cannot be adequately tested without knowledge of the quantitative relationship between P-CheY and bacterial swimming behavior. A computerized image analysis system was developed to collect extensive statistics on freeswimming and individual tethered cells. P-CheY levels were systematically varied by controlled expression of CheY in an E.coli strain lacking the CheY phosphatase, CheZ, and the receptor demethylating enzyme CheB. Tumbling frequency was found to vary with P-CheY concentration in a weakly sigmoidal fashion (apparent Hill coefficient approximately 2.5). This indicates that the high sensitivity of the chemotaxis system is not derived from highly cooperative interactions between P-CheY and the flagellar motor, but rather depends on nonlinear effects within the chemotaxis signal transduction network. The complex relationship between single flagella rotation and free-swimming behavior was examined; our results indicate that there is an additional level of information processing associated with interactions between the individual flagella. An allosteric model of the motor switching process is proposed which gives a good fit to the observed switching induced by P-CheY. Thus the level of intracellular P-CheY can be estimated from behavior determinations: approximately 30% of the intracellular pool of CheY appears to be phosphorylated in fully adapted wild-type cells.

Bacterial Proteins↗
PubMed2006

Analysis and implementation of a neural extended Kalman filter for target tracking.

Having a better motion model in the state estimator is one way to improve target tracking performance. Since the motion model of the target is not known a priori, either robust modeling techniques or adaptive modeling techniques are required. The neural extended Kalman filter is a technique that learns unmodeled dynamics while performing state estimation in the feedback loop of a control system. This coupled system performs the standard estimation of the states of the plant while estimating a function to approximate the difference between the given state-coupling function model and the behavior of the true plant dynamics. At each sample step, this new model is added to the existing model to improve the state estimate. The neural extended Kalman filter has also been investigated as a target tracking estimation routine. Implementation issues for this adaptive modeling technique, including neural network training parameters, were investigated and an analysis was made of the quality of performance that the technique can have for tracking maneuvering targets.

Computer Simulation↗
PubMedDate not supplied

Mechanoelectrical and voltage-gated ion channels in mammalian vestibular hair cells.

Mammalian vestibular afferents respond robustly to head movements at low frequencies and provide input to reflexes that control eye, head and body position. Vestibular organs have distinctive regions and hair cells: Type II cells receive bouton afferent endings and type I cells receive large calyx afferent endings. In the rodent utricle, type II cells are broadly tuned to frequencies between 10 and 30 Hz. Other recent data suggest that otolith organs function in this frequency range, which is higher than previously imagined. Some of the tuning derives from adaptation of the transducer current, which is best fitted with a double exponential decay with time constants of approximately 4 and 40 ms. Further tuning is provided by basolateral conductances, principally outwardly rectifying, voltage-gated K+ conductances. The kinetics of the K+ currents tend to vary with location in the sensory epithelium and therefore may contribute to regional variation in afferent physiology. Type I hair cells have a large, negatively activating K+ conductance, g(K,L), that confers a very low input resistance and therefore attenuates the receptor potential. This may reduce nonlinearity in the receptor potential, a possibly useful feature for the motor reflexes served by the vestibular system. On the other hand, the small receptor potentials together with unusually negative resting potentials are hard to reconcile with calcium-mediated quantal transmission. This problem may be overcome by factors that inhibit g(K,L)'s activation at resting potential. Also, the calyx may support nonquantal transmission.

Animals↗
PubMed1998

Contributions of roll and pitch to sea sickness.

The purpose of this study was to test the traditional assumption that sea sickness is uniquely provoked by heave motion characteristics, with pitch and roll movements being ineffective. In an experiment with a ship motion simulator, subjects were exposed to pitch and roll motions in combination with rather weak heave motions that have no motion sickness-inducing potential. Very high levels of motion sickness were observed (with a motion sickness rating scale) in almost 50% of our subjects. In three control experiments, it was shown that these heave motions, when presented separately, indeed have no motion sickness-inducing potential and that pitch and roll motions presented alone or in combination with each other have only a very small motion sickness-inducing potential. These results indicate that pitch and roll when combined with small heave motions, which in themselves are not sickness provoking, produce more motion sickness than claimed by the classic models. This suggests that in models on motion sickness, pitch and roll should be combined in a nonlinear fashion with heave and that such models will remain rather crude if they do not include a description of the vestibular contribution to motion sickness.

Adaptation, Physiological↗
PubMed1985

Cat retinal ganglion cell receptive-field alterations after 6-hydroxydopamine induced dopaminergic amacrine cell lesions.

Optic tract single-unit recordings were used to study ganglion cell response functions of the intact cat eye after 6-hydroxydopamine (6-OHDA) lesioning of the dopaminergic amacrine cell (AC) population of the inner retina. The impairment of the dopaminergic AC was verified by high pressure-liquid chromatography (HPLC) with electrochemical detection of endogenous dopamine content and by [3H]dopamine high-affinity uptake; the dopaminergic ACs of the treated eyes demonstrated reduced endogenous dopamine content and reduced [3H]dopamine uptake compared with that of their matched controls. Normal appearing [3H]GABA and [3H]-glycine uptake in the treated retinas suggests the absence of any nonspecific action of the 6-OHDA on the neural retina. The impairment of the dopaminergic AC population was found to alter a number of response properties in off-center ganglion cells, but this impairment had only a modest effect on the on-center cells. An abnormally high proportion of the off-center ganglion cells in the 6-OHDA treated eyes possessed nonlinear, Y-type receptive fields. These cells also possessed shift-responses of greater than normal amplitude, altered intensity-response functions, reduced maintained activities, and more transient center responses. Of the on-center type cells, only the Y-type on-center cells were affected by 6-OHDA, possessing higher than normal maintained activities and altered intensity-response functions. The on-center X-cells were unaffected by 6-OHDA treatment. The dopaminergic AC of the photopically adapted cat retina therefore modulates a number of ganglion cell response properties and within the limits of this study is most prominent in off-center ganglion cell circuitry. When functioning normally, the dopaminergic AC of the cat's retina appears to make the receptive field of the off-center cell more sustained and may make its spatial summation characteristics more linear while adjusting the intensitive properties of neurons in both the on- and off-center pathways.

Animals↗
PubMed1985

Comparative pharmacokinetics and pharmacodynamics of lorazepam, alprazolam and diazepam.

The contribution of differential absorption-distribution pharmacokinetics to drug activity can be partially determined by comparing simultaneous estimates of drug serum level with pharmacodynamic effects. In the present paper we have contrasted the effects of clinically equipotent doses of lorazepam, alprazolam, and diazepam on the performance of tracking and digit symbol substitution tasks. Eight young males were tested for 12 h after ingesting the drug. The three benzodiazepines and placebo were administered to each subject according to a balanced double-blind Latin square design. A model is presented that describes the relationship between drug concentration and the degree of impairment across time after the final peak effect. Exponential rate constants were determined for each drug using a Marquardt nonlinear fit of the pooled data. Basically, the constants relate offset serum drug values to the impairment curves at a time when serum-brain equilibrium is assumed to have occurred. The values indicate markedly rapid acute tolerance for alprazolam and diazepam but relatively little acute tolerance for lorazepam. Whether these constants reflect adaptation or differential association-dissociation receptor rate constants cannot be determined, but they do highlight the need to consider receptor kinetics as an important factor in benzodiazepine pharmacodynamics.

Adult↗
PubMed1992

Functional determinants of bone structure: beyond Wolff's law of bone transformation.

Frost has suggested that functional loading controls bone mass and form as a thermostat controls temperature--by homeostatic regulation (i.e., by negative feedback). Yet, the literature contains many results that appear incompatible with the "mechanostat" hypothesis. We propose that a different type of regulation--epigenetic--is important in many aspects of bone adaptation. Epigenetic regulation, as we describe it, involves positive feedback loops and promotes differentiation as it forces elements of a system to choose between two extreme levels called attractors. Our review of bone adaptation data suggests that lamellar bone formation is regulated homeostatically, whereas the formation of woven-fibered bone or fracture callus is regulated epigenetically, that is, woven bone formation is brought about by a positive feedback loop that stimulates osteoblasts to a state of greater individual activity. This positive feedback loop may involve transforming growth factor beta (TGF beta), for which autocrine induction has been demonstrated in vivo, as well as other factors, including insulin-like growth factor (IGF) and prostaglandin E2 (PGE2). The importance of this model is that it provides a mechanism for many unexplained nonlinear events that have been observed in bone adaptation experiments. Furthermore, it provides insights into the genesis of woven bone, which is a critical step in the process of bone healing and regeneration.

Animals↗