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Care of the self and patient participation in genetic discourse: a Foucauldian reading of the surgeon general's "my family health portrait" program.

Critics of genetic discourse are concerned that deterministic and discriminatory views of genetics are increasingly becoming adopted. These views argue that current genetic discourse becomes a source of power whereby powerful institutions harm people with so-called "bad" genes. This essay argues that current analyses of the power of genetics discourse are grounded in an improper reading that disempowers patients. Deploying Michel Foucault's concept "care of the self," this essay claims that genetics discourse is better understood as a way that patients take on power through rhetoric rather than a force that has power over patients. Through a close reading of the "My Family Health Portrait" program, this paper argues that patients experience a process of "subjection" wherein they become agents of and objects of genetics discourse both. This alternative mode of analyzing the power of genetics discourse has implications for our collective understanding of the operations of the care of the self and the uses of genetic information that we propose.

Awareness↗

Probability density methods for smooth function approximation and learning in populations of tuned spiking neurons.

This article proposes a new method for interpreting computations performed by populations of spiking neurons. Neural firing is modeled as a rate-modulated random process for which the behavior of a neuron in response to external input can be completely described by its tuning function. I show that under certain conditions, cells with any desired tuning functions can be approximated using only spike coincidence detectors and linear operations on the spike output of existing cells. I show examples of adaptive algorithms based on only spike data that cause the underlying cell-tuning curves to converge according to standard supervised and unsupervised learning algorithms. Unsupervised learning based on principal components analysis leads to independent cell spike trains. These results suggest a duality relationship between the random discrete behavior of spiking cells and the deterministic smooth behavior of their tuning functions. Classical neural network approximation methods and learning algorithms based on continuous variables can thus be implemented within networks of spiking neurons without the need to make numerical estimates of the intermediate cell firing rates.

Action Potentials↗

A stochastic model for predator-prey systems: basic properties, stability and computer simulation.

A simple stochastic description of a model of a predator-prey system is given. The evolution of the system is described by means of Itô's stochastic differential equations (SDEs), which are the natural stochastic generalization of the Lotka-Volterra deterministic differential equations. Since these SDEs do not satisfy the usual conditions for the existence and uniqueness of the solution, we state a theorem of existence; moreover we study the stability of the equilibrium point and perform a computer simulation to study the behaviour of the trajectories of solutions with given initial data and to estimate first and second moments.

Animals↗

Effects of aquifer heterogeneity and reaction mechanism uncertainty on a reactive barrier.

This paper addresses impacts of aquifer heterogeneity and reaction mechanism uncertainty on permeable reactive barrier (PRB) performance and describes modeling tools and preliminary guidelines for risk-based design of reactive barriers at heterogeneous sites. A braided stream aquifer was generated stochastically, using a fixed correlation structure and four levels of variability in the hydraulic conductivity field. A vertical, homogeneous barrier was placed in the aquifer. Based on a deterministic design, the size of the PRB for uniform conditions was considered conservative (factor of safety=3.3). Monte Carlo simulation was used to model cis 1,2-DCE reduction by iron metal with uncertainty in the reaction mechanism rate constants. These results were combined with flow and particle tracking results to predict the spatial distribution and flow-averaged concentrations of cis 1,2-DCE and vinyl chloride at the exit face of the PRB. Evaluated on a risk basis, the deterministic design method was found to be unconservative for more heterogeneous aquifers. Uncertainty in the reaction mechanism accentuated the negative effects of aquifer heterogeneity. Several compensating factors that may reduce the vulnerability of reactive barriers to aquifer heterogeneity are discussed.

Carcinogens↗

Female mate-choice behavior and sympatric speciation.

Many models have investigated how the process of speciation may occur in sympatry. In these models, individuals are either asexual or mate choice is determined by very simple rules. Females, for example, may be assumed either to compare their phenotype to that of a potential mate, preferring to mate with similar males (phenotype matching), or to possess preference genes that determine which male phenotype they prefer. These rules often do not reflect the mate-choice rules found in empirical studies. In this paper, we compare these two modes of female choice with various types of sexual imprinting. We examine the efficacy of different mate-choice behavior in causing divergence in male traits under simple deterministic one-locus population genetic models as well as under polygenic, individual-based simulations based on the models of Dieckmann and Doebeli (1999). We find that the inheritance mechanism of mate choice can have a large effect on the ease of sympatric speciation. When females imprint on their mothers, the result of the model is similar to phenotype matching, where speciation can occur fairly easily. When females imprint on their fathers or imprint obliquely, speciation becomes considerably less likely. Finally, when females rely on preference genes, male trait evolution occurs easily, but the correlation between trait and preference can be weak, and interpreting these results as speciation may be suspect.

Animals↗

Heart rate variability in the human transplanted heart: nonlinear dynamics and QT vs RR-QT alterations during exercise suggest a return of neurocardiac regulation in long-term recovery.

RATIONALE: Functional reinnervation of the transplanted human heart by the autonomic nervous system has not been demonstrated. A lack of autonomic control of the transplanted allograft is reflected by an increased resting heart rate, a sluggish heart rate response to dynamical exercise and a reduced heart rate variability. Recent evidence suggests that a measure of deterministic chaos in the heartbeat interval series (point correlation dimension, PD2i) is superior to the conventional power spectrum or other stochastic measures in detecting changes in the mechanism underlying heartbeat generation. METHODS: The PD2i is based on the presumption that the variability is determined and patterned, whereas the stochastic measures all assume that the variability is around a stationary mean and is noise. The PD2i reconstructs the degrees of freedom (number of independent variables) in the system that generates the time series examined, and does this irrespective of whether the system is stochastic or deterministic and is stationary in time. RESULTS: PD2i was determined for heartbeat intervals (RR, ECG digitized at 1200 Hz; supine posture) of 23 heart transplant recipients (HTR: 9 adults, 14 children; 0.04-7.7 years after transplantation) and 21 healthy control subjects (CTL; 13 adults, 8 children). The PD2i (+/-SD) averaged 5.4 +/- 0.7 for the CTL adults and 5.4 +/- 0.6 for the CTL children. Mean PD2i was reduced after transplantation to 1.1 +/- 0.1 in 6 HTRs recorded within 1 year after surgery; in one HTR recorded 2 weeks after surgery the mean PD2i was 3.7. Between 1 to 2 years PD2i was found increased in 2 of 3 subjects and between 2 to 8 years it was increased in 13 of 13, but not to control levels. In normal hearts the QT subinterval of each heartbeat cycle is associated with inotropy and the RR-QT remainder with chronotropy (i.e., the dyastolic interval during which RR is primarily regulated). To examine more closely the residual and returning heartbeat dynamics of the HTR subjects, these subinterval series were examined during mild exercise (40 to 90 Watts) and its recovery. In recent HTRs, resting QT and RR-QT were moderately reduced and modulated by exercise and recovery, but with an approximate 100 beat latency. In long-term (7-8 years) HTR subjects there was a rapid and larger response to exercise/recovery, but compared to normal the range was smaller and the complexity of the subinterval trajectories in time was simpler. CONCLUSIONS: Recurrence of low-dimensional deterministic dynamics after transplantation suggests recovery of neurocardiac control attributable to 1) reorganization of the viable intrinsic cardiac nervous system, 2) reinnervation by the extrinsic autonomic nervous system, or 3) both.

Adult↗

Application of the queueing theory with Monte Carlo simulation to inhalation toxicology.

Various models have been developed in modelling of inhalation toxicology. The deterministic approach, which has been used to date in most of the models, needs to consider numerous factors, e.g. anatomical structure, breathing frequency, humidity, metabolism rate, partition coefficients, pulmonary ventilation, perfusion rates, unidirectional/cyclic air flow, non-steady-state, steady-state, etc. In the present study, a stochastic approach was used in the modelling of inhalation toxicology, because there is a phenomenological analogy between the queueing system and respiratory system dealing with inhaled toxicants. Using the queueing theory, the amounts of toxicants in the respiratory system, the time needed to remove the accumulated amounts of toxicants from the respiratory system, etc. can be estimated. The Monte Carlo simulation of queueing process was performed to analyse cigarette smoking, and shows the potential use of the queueing theory in inhalation toxicology.

Administration, Inhalation↗

Stochasticity, invasions, and branching random walks.

We link deterministic integrodifference equations to stochastic, individual-based simulations by means of branching random walks. Using standard methods, we determine speeds of invasion for both average densities and furthest-forward individuals. For density-independent branching random walks, demographic stochasticity can produce extinction. Demographic stochasticity does not, however, reduce the overall asymptotic speed of invasion or preclude continually accelerating invasions.

Probability↗

Complete calibration of a stereo photogrammetric system through control points of unknown coordinates.

This paper presents a new method for calibrating a video 3D stereo-photogrammetric system. The external parameters and the focal lengths of the cameras are determined from the epipolar constraint and the principal points are computed through the minimisation of a cost function carried out through an evolutionary optimisation. The method has been made more robust with a deterministic annealing procedure of the search region amplitude. Calibration is carried out by moving a rigid bar, carrying two markers on its extremities, inside the working volume. The distance between the two markers is the only measure required. Tests on real data are reported which show that the obtained accuracy is comparable to the one achieved calibrating with control points of known 3D coordinates.

Calibration↗

Correlation entropy of synaptic input-output dynamics.

The responses of synapses in the neocortex show highly stochastic and nonlinear behavior. The microscopic dynamics underlying this behavior, and its computational consequences during natural patterns of synaptic input, are not explained by conventional macroscopic models of deterministic ensemble mean dynamics. Here, we introduce the correlation entropy of the synaptic input-output map as a measure of synaptic reliability which explicitly includes the microscopic dynamics. Applying this to experimental data, we find that cortical synapses show a low-dimensional chaos driven by the natural input pattern.

Action Potentials↗

Direct solution of continuous densities given the Fourier magnitudes.

In order to apply direct methods routinely to macromolecular crystals it will be necessary to generate a non-atomic theory which is applicable to continuous densities. Reformulation of the 'phase problem' in terms of deconvoluting an autocorrelation function or Patterson synthesis reduces the problem from a theoretically intractable transcendental problem to a system of simultaneous quadratic equations. These quadratic equations may, in principle, always be solved by conjugate direction search techniques. The phase problem is shown to be a class P problem, admitting a deterministic solution in polynomial time. Two algorithms are presented with running times proportional to N2points and Npoints log Npoints per step. These algorithms are a pixel-by-pixel search and a conjugate gradients search. When the data are exact and complete the Fourier magnitudes are readily inverted by them to find the image. An example with real data, from a 15mer of DNA, is also shown.

DNA↗

Randomization in substance abuse clinical trials.

BACKGROUND: A well designed randomized clinical trial rates as the highest level of evidence for a particular intervention's efficacy. Randomization, a fundamental feature of clinical trials design, is a process invoking the use of probability to assign treatment interventions to patients. In general, randomization techniques pursue the goal of providing objectivity to the assignment of treatments, while at the same time balancing for treatment assignment totals and covariate distributions. Numerous randomization techniques, each with varying properties of randomness and balance, are suggested in the statistical literature. This paper reviews common randomization techniques often used in substance abuse research and an application from a National Institute on Drug Abuse (NIDA)-funded clinical trial in substance abuse is used to illustrate several choices an investigator faces when designing a clinical trial. RESULTS: Comparisons and contrasts of randomization schemes are provided with respect to deterministic and balancing properties. Specifically, Monte Carlo simulation is used to explore the balancing nature of randomization techniques for moderately sized clinical trials. Results demonstrate large treatment imbalance for complete randomization with less imbalance for the urn or adaptive scheme. The urn and adaptive randomization methods display smaller treatment imbalance as demonstrated by the low variability of treatment allocation imbalance. For all randomization schemes, covariate imbalance between treatment arms was small with little variation between adaptive schemes, stratified schemes and unstratified schemes given that sample sizes were moderate to large. CONCLUSION: We develop this paper with the goal of reminding substance abuse researchers of the broad array of randomization options available for clinical trial designs. There may be too quick a tendency for substance abuse researchers to implement the fashionable urn randomization schemes and other highly adaptive designs. In many instances, simple or blocked randomization with stratification on a major covariate or two will accomplish the same objectives as an urn or adaptive design, and it can do so with more simply implemented schedules and without the dangers of overmatching. Furthermore, the proper analysis, fully accounting for the stratified design, can be conducted.

Humans↗

A stochastic model of oscillatory blood testosterone levels.

A continuous-time, discrete-state stochastic model of testosterone secretion in men is considered. Blood levels of testosterone in men fluctuate periodically with a period of 2-3 h. The deterministic model, on which the stochastic model considered here is based, is well studied and has been shown to have a globally stable fixed point. Thus, no sustained oscillations are possible in the deterministic case. However, the stochastic model does observe periodic, pulsatile behavior. This demonstrates how oscillations can occur due to a switching behavior dependent on the random degradation of testosterone molecules in the system. The Gillespie algorithm is used to simulate the hormone secretion model. Important parameters of the model are discussed and results from the model are compared to experimental observations.

Biological Clocks↗

Quantitative analysis of electroencephalograms: is there chaos in the future?

The history of quantitative, computerized electroencephalogram (EEG) analysis is reviewed. It is shown that, until very recently, the basic approach to EEG analysis involved the assumption that the EEG is stochastic. Consequently, statistical pattern recognition techniques, segmentation procedures, syntactic methods, knowledge-based approaches, and even artificial neural network methods have been developed with different levels of success. A fundamentally different approach to computerized EEG analysis, however, is making its way into the laboratories. The basic idea, inspired by recent advances in the area of non-linear dynamics, and especially the theory of chaos, is to view an EEG as the output of a deterministic system of relatively simple complexity, but containing non-linearities. This suggests that studying the geometrical dynamics of EEGs, and the development of neurophysiologically realistic models of EEG generation may produce more successful automated EEG analysis techniques than the classical, stochastic methods. Evidence supporting the non-linear dynamics paradigm is reviewed, and possible research paths are indicated.

Algorithms↗

Stochastic and deterministic models for SIS epidemics among a population partitioned into households.

Models for the spread of an SIS epidemic among a population consisting of m households, each containing n individuals, are considered and their behaviour is analysed under the practically relevant situation when m is large and n small. A threshold parameter R* is determined. For the stochastic model it is shown that the epidemic has a non-zero probability of taking off if and only if R* > 1, and the extension to unequal household sizes is also considered. For the deterministic model, with households of size 2, it is shown that if R* < or = 1 then the epidemic dies out, whilst if R* > 1 the epidemic settles down to an endemic equilibrium. The usual basic reproductive ratio R0 does not provide a good indicator for the behaviour of these household epidemic models unless the household size n is large.

Endemic Diseases↗

Metapopulation theory for fragmented landscapes.

We review recent developments in spatially realistic metapopulation theory, which leads to quantitative models of the dynamics of species inhabiting highly fragmented landscapes. Our emphasis is in stochastic patch occupancy models, which describe the presence or absence of the focal species in habitat patches. We discuss a number of ecologically important quantities that can be derived from the full stochastic models and their deterministic approximations, with a particular aim of characterizing the respective roles of the structure of the landscape and the properties of the species. These quantities include the threshold condition for persistence, the contributions that individual habitat patches make to metapopulation dynamics and persistence, the time to metapopulation extinction, and the effective size of a metapopulation living in a heterogeneous patch network.

Animals↗

Texture decomposition by harmonics extraction from higher order statistics.

In this paper, a method of harmonics extraction from Higher Order Statistics (HOS) is developed for texture decomposition. We show that the diagonal slice of the fourth-order cumulants is proportional to the autocorrelation of a related noiseless sinusoidal signal with identical frequencies. We propose to use this fourth-order cumulants slice to estimate a power spectrum from which the harmonic frequencies can be easily extracted. Hence, a texture can be decomposed into deterministic components and indeterministic components as in a unified texture model through a Wold-like decomposition procedure. The simulation and experimental results demonstrated that this method is effective for texture decomposition and it performs better than traditional lower order statistics based decomposition methods.

Algorithms↗

Models of the inositol trisphosphate receptor.

The inositol (1,4,5)-trisphosphate receptor (IPR) plays a crucial role in calcium dynamics in a wide range of cell types, and is often a central feature in quantitative models of calcium oscillations and waves. We review deterministic and stochastic mathematical models of the IPR, from the earliest ones of the 1970s and 1980s, to the most recent. The effects of IPR stochasticity on Ca2+ dynamics are briefly discussed.

Allosteric Site↗