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Biomedical subjects

T J Newman

Publications and source records attributed to T J Newman.

At least 19 recordsLinked to original sources

Many-body theory of chemotactic cell-cell interactions.

We consider an individual-based stochastic model of cell movement mediated by chemical signaling fields. This model is formulated using Langevin dynamics, which allows an analytic study using methods from statistical and many-body physics. In particular we construct a diagrammatic framework within which to study cell-cell interactions. In the mean-field limit, where statistical correlations between cells are neglected, we recover the deterministic Keller-Segel equations. Within exact perturbation theory in the chemotactic coupling epsilon , statistical correlations are non-negligible at large times and lead to a renormalization of the cell diffusion coefficient D(R)--an effect that is absent at mean-field level. An alternative closure scheme, based on the necklace approximation, probes the strong coupling behavior of the system and predicts that D(R) is renormalized to zero at a critical value of epsilon, indicating self-localization of the cell. Stochastic simulations of the model give very satisfactory agreement with the perturbative result. At higher values of the coupling simulations indicate that D(R) approximately epsilon(-2) , a result at odds with the necklace approximation. We briefly discuss an extension of our model, which incorporates the effects of short-range interactions such as cell-cell adhesion.

Algorithms↗

Stochastic models in population biology and their deterministic analogs.

We introduce a class of stochastic population models based on "patch dynamics." The size of the patch may be varied, and this allows one to quantify the departures of these stochastic models from various mean-field theories, which are generally valid as the patch size becomes very large. These models may be used to formulate a broad range of biological processes in both spatial and nonspatial contexts. Here, we concentrate on two-species competition. We present both a mathematical analysis of the patch model, in which we derive the precise form of the competition mean-field equations (and their first-order corrections in the nonspatial case), and simulation results. These mean-field equations differ, in some important ways, from those which are normally written down on phenomenological grounds. Our general conclusion is that mean-field theory is more robust for spatial models than for a single isolated patch. This is due to the dilution of stochastic effects in a spatial setting resulting from repeated rescue events mediated by interpatch diffusion. However, discrete effects due to modest patch sizes lead to striking deviations from mean-field theory even in a spatial setting.

Adaptation, Physiological↗

Accurate discretization of advection-diffusion equations.

We present an exact mathematical transformation which converts a wide class of advection-diffusion equations into a form allowing simple and direct spatial discretization in all dimensions, and thus the construction of accurate and more efficient numerical algorithms. These discretized forms can also be viewed as master equations which provide an alternative mesoscopic interpretation of advection-diffusion processes in terms of diffusion with spatially varying hopping rates.

Journal Article↗

Population dynamics with global regulation: the conserved Fisher equation.

We introduce and study a conserved version of the Fisher equation. Within a population biology context, this model describes spatially extended populations in which the total number of individuals is fixed due to either biotic or environmental factors. We find a rich spectrum of dynamical phases including a pseudotraveling wave and, in the presence of the Allee effect, a phase transition from a locally constrained high density state to a low density fragmented state.

Models, Biological↗

Extinction times and moment closure in the stochastic logistic process.

We investigate the statistics of extinction times for an isolated population, with an initially modest number M of individuals, whose dynamics are controlled by a stochastic logistic process (SLP). The coefficient of variation in the extinction time V is found to have a maximum value when the death and birth rates are close in value. For large habitat size K we find that Vmax is of order K1/4 / M1/2, which is much larger than unity so long as M is small compared to K1/2. We also present a study of the SLP using the moment closure approximation (MCA), and discuss the successes and failures of this method. Regarding the former, the MCA yields a steady-state distribution for the population when the death rate is low. Although not correct for the SLP model, the first three moments of this distribution coincide with those calculated exactly for an adjusted SLP in which extinction is forbidden. These exact calculations also pinpoint the breakdown of the MCA as the death rate is increased.

Animals↗

Population dynamics with a refuge: fractal basins and the suppression of chaos.

We consider the effect of coupling an otherwise chaotic population to a refuge. A rich set of dynamical phenomena is uncovered. We consider two forms of density dependence in the active population: logistic and exponential. In the former case, the basin of attraction for stable population growth becomes fractal, and the bifurcation diagrams for the active and refuge populations are chaotic over a wide range of parameter space. In the case of exponential density dependence, the dynamics are unconditionally stable (in that the population size is always positive and finite), and chaotic behavior is completely eradicated for modest amounts of dispersal. We argue that the use of exponential density dependence is more appropriate, theoretically as well as empirically, in a model of refuge dynamics.

Ecology↗

Critical dimensions of the diffusion equation.

We study the evolution of a random initial field under pure diffusion in various space dimensions. From numerical calculations we find that the persistence properties of the system show sharp transitions at critical dimensions d(1) approximately 26 and d(2) approximately 46. We also give refined measurements of the persistence exponents for low dimensions.

Journal Article↗

Binary data corruption due to a Brownian agent.

We introduce a model of binary data corruption induced by a Brownian agent (active random walker) on a d-dimensional lattice. A continuum formulation allows the exact calculation of several quantities related to the density of corrupted bits rho, for example, the mean of rho and the density-density correlation function. Excellent agreement is found with the results from numerical simulations. We also calculate the probability distribution of rho in d=1, which is found to be log normal, indicating that the system is governed by extreme fluctuations.

Journal Article↗

Binary data corruption due to a Brownian agent. II. Two dimensions, competing agents, and generalized couplings.

This work is a continuation of our previous investigation of binary data corruption due to a Brownian agent [Phys. Rev. E 59, 5172 (1999)]. We extend our study in three main directions which allow us to make closer contact with real bistable systems. These are (i) a detailed analysis of two dimensions, (ii) the case of competing agents, and (iii) the cases of asymmetric and quenched random couplings. Most of our results are obtained by extending our original phenomenological model, and are supported by extensive numerical simulations.

Journal Article↗

Sign-time distributions for interface growth.

We apply the recently introduced distribution of sign-times (DST) to nonequilibrium interface growth dynamics. We are able to treat within a unified picture the persistence properties of a large class of relaxational and noisy linear growth processes, and prove the existence of a nontrivial scaling relation. A critical dimension is found, relating to the persistence properties of these systems. We also illustrate, by means of numerical simulations, the different types of DST to be expected in both linear and nonlinear growth mechanisms.

Journal Article↗

Effects of captopril on survival in patients with heart failure.

Results from a large multicenter study and from the published literature suggest that captopril can improve survival in patients with advanced heart failure. The survival status of 105 patients with moderately severe heart failure who participated in a multicenter, double-blind comparison of captopril and placebo therapy was ascertained on an intention-to-treat basis. During the 90-day double-blind portion of this study, 21 percent (11 of 52 patients) of placebo-assigned patients died compared with four percent (two of 53 patients) of captopril-assigned patients (p less than 0.01). In addition, six previously published studies that provided comparative mortality data were identified. In one of these, the survival rate was reported to be improved in those who received captopril; in the other five studies, no conclusion could be drawn with respect to survival since death was an infrequent event within all treatment groups. Mechanisms by which captopril may improve survival include its favorable effects on hemodynamic parameters, its association with reduced ventricular ectopic activity, and its inhibitory effects on the renin-angiotensin and sympathetic nervous systems.

Captopril↗

Efficacy and safety of captopril in the treatment of severe childhood hypertension: report of the International Collaborative Study Group.

The safety and efficacy of captopril therapy in children with severe and refractory hypertension has been evaluated in a collaborative international study which enrolled a group of 73 patients, 15 years of age or younger. Most patients had hypertension associated with renal disease or vascular abnormalities. Captopril was administered for periods of less than 3 months to more than 1 year. A significant decrease in both systolic and diastolic blood pressures was produced by the administration of captopril, usually in conjunction with other antihypertensive agents (most commonly diuretics and/or beta-blockers). Systolic blood pressures were normalized in 62% and 53% and diastolic blood pressures in 56% and 45% of reported patients after the second and sixth months of captopril therapy, respectively. The response to captopril was sustained over a 12-month period. Adverse reactions were reported in 49% of the 73 patients; 48% of patients had experienced adverse reactions to other antihypertensive agents prior to entering the study. The reactions most frequently observed during captopril therapy were hypotension, vomiting, postural symptoms, anemia, rash, and anorexia. Leukopenia was reported in six patients, all of whom had renal impairment. Two of these patients had received concomitant therapy with immunosuppressants, and one had systemic lupus erythematosus. Captopril was discontinued in two of these six children. Statistically significant increases in mean serum urea nitrogen and potassium concentrations and decreases in mean serum CO2 levels were observed during the course of therapy. These effects could not be exclusively attributed to captopril administration as the study population received multidrug therapy and had significant intrinsic disease. Captopril was demonstrated to be an effective and safe drug for the treatment of children with severe hypertension.

Adolescent↗

Adrenal scan in 17-alpha-hydroxylase deficiency: false indication of adrenal adenoma.

A patient who was thought to have testicular feminization syndrome and primary aldosteronism had an adrenal scan that suggested an adrenal adenoma. After later diagnosis of 17-alpha-hydroxylase deficiency, she was treated with glucocorticoids rather than surgery. Her clinical course and a repeat adrenal scan confirmed she did not have a tumor.

Adenoma↗

Acetaminophen hepatotoxicity and malnutrition.

A patient with severe anorexia nervosa, who ingested 15 gm. of acetaminophen, was treated with oral N-acetylcysteine. Contrary to suggestions in the literature that malnutrition increases the susceptibility of patients to the hepatotoxic effects of acetaminophen this patient survived without evidence of liver damage. Changes in the metabolism of acetaminophen secondary to poor nutrition may explain the benign course in this and similar patients.

Acetaminophen↗