Michael R. Swift

Incidence of Cancer in 161 Families Affected by Ataxia–Telangiectasia

BACKGROUND Ataxia-telangiectasia is an autosomal recessive syndrome in which cancers develop in affected homozygotes at a rate approximately 100 times higher than in unaffected age-matched subjects. Retrospective studies have shown that persons heterozygous for the ataxia-telangiectasia gene, who make up about 1 percent of the general population, also have an excess risk of cancer, particularly breast cancer in women. Patients with ataxia-telangiectasia and cells derived from homozygotes and heterozygotes are unusually sensitive to ionizing radiation. METHODS Cancer incidence and mortality, mortality from ischemic heart disease, and mortality from all causes were compared prospectively for a mean of 6.4 years in 1599 adult blood relatives of patients with ataxia-telangiectasia and 821 of their spouses, who served as controls, in 161 families affected by ataxia-telangiectasia. In a case-control substudy, we compared documented occupational and fluoroscopic diagnostic exposures to radiation in the 19 female blood relatives in whom breast cancer was first diagnosed during the period of prospective observation with the exposures in 57 matched blood relatives who did not have breast cancer. RESULTS Cancer rates were significantly higher in the group of blood relatives than in their spouses, specifically in the subgroup of 294 blood relatives who were known to be heterozygous for the ataxia-telangiectasia gene. The estimated risk of cancer of all types among heterozygotes as compared with noncarriers was 3.8 in men and 3.5 in women, and that for breast cancer in women was 5.1. Among the blood relatives, women with breast cancer were more likely to have been exposed to selected sources of ionizing radiation than controls without cancer (odds ratio = 5.8, P = 0.005). Male and female blood relatives also had 3-fold and 2.6-fold excess mortality from all causes, respectively, from the ages of 20 through 59 years. CONCLUSIONS The ataxia-telangiectasia gene predisposes heterozygotes to cancer, particularly breast cancer in women. There is also excess mortality from all causes in adults under the age of 60. Diagnostic or occupational exposure to ionizing radiation probably increases the risk of breast cancer in women heterozygous for ataxia-telangiectasia.

Lattice Boltzmann simulation of nonideal fluids.

A lattice Boltzmann scheme able to model the hydrodynamics of phase separation and two-phase flow is described. Thermodynamic consistency is ensured by introducing a non-ideal pressure tensor directly into the collision operator. We also show how an external chemical potential can be used to supplement standard boundary conditions in order to investigate the effect of wetting on phase separation and fluid flow in confined geometries. The approach has the additional advantage of reducing many of the unphysical discretisation problems common to previous lattice Boltzmann methods.

Scaling forces to asteroid surfaces: The role of cohesion

The scaling of physical forces to the extremely low ambient gravitational acceleration regimes found on the surfaces of small asteroids is performed. Resulting from this, it is found that van der Waals cohesive forces between regolith grains on asteroid surfaces should be a dominant force and compete with particle weights and be greater, in general, than electrostatic and solar radiation pressure forces. Based on this scaling, we interpret previous experiments performed on cohesive powders in the terrestrial environment as being relevant for the understanding of processes on asteroid surfaces. The implications of these terrestrial experiments for interpreting observations of asteroid surfaces and macro-porosity are considered, and yield interpretations that differ from previously assumed processes for these environments. Based on this understanding, we propose a new model for the end state of small, rapidly rotating asteroids which allows them to be comprised of relatively fine regolith grains held together by van der Waals cohesive forces.

Diabetes Mellitus in Ataxia-Telangiectasia, Fanconi Anemia, Xeroderma Pigmentosum, Common Variable Immune Deficiency, and Severe Combined Immune Deficiency Families

The hypothesis that heterozygous carriers of genes for certain autosomal recessive syndromes may be predisposed to diabetes was tested by comparing diabetes incidence from age 20 to 69 yr in blood relatives to that in spouse controls among 7999 adult family members of patients with one of five autosomal recessive syndromes: ataxia-telangiectasia (A-T), Fanconi anemia (FA), xeroderma pigmentosum (XP), common variable immune deficiency (CVID), and severe combined immune deficiency (SCID). FA and A-T families were studied because earlier findings in family members and the frequency of diabetes in homozygotes suggested that heterozygotes might also be predisposed to diabetes. The XP, CVID, and SCID families were included to see what analysis of family data would reveal when there was no prior evidence for a gene-diabetes association. The diabetes rate ratios of 2.6 and 4.2 among FA and SCID females, respectively, were significantly elevated. For female FA heterozygotes specifically, the estimated relative risk of 5.1 for developing diabetes was also significantly elevated. Among males, the most pronounced, although not statistically significant, findings were an elevated rate ratio of 2.2 for A-T males and a low-rate ratio of 0.5 for CVID males. The results suggest that heterozygotes for some of the diabetes-associated autosomal recessive syndromes may themselves be predisposed to diabetes.

Diabetes Mellitus and the Gene for Fanconi's Anemia

An increased prevalence of diabetes mellitus has been found in relatives of eight probands homozygous for the rare recessive syndrome Fanconis anemia. Since many of these relatives are expected to be heterozygous for the gene for Fanconis anemia, this gene may predispose to diabetes in single dose.

Glassy behavior in a ferromagnetic p -spin model

Recent work has suggested the existence of glassy behavior in a ferromagnetic model with a four-spin interaction. Motivated by these findings, we have studied the dynamics of this model using Monte Carlo simulations with particular attention being paid to two-time quantities. We find that the system shares many features in common with glass forming liquids. In particular, the model exhibits: (i) a very long-lived metastable state, (ii) autocorrelation functions that show stretched exponential relaxation, (iii) a non-equilibrium timescale that appears to diverge at a well defined temperature, and (iv) low temperature aging behaviour characteristic of glasses.

Scaling of the random-field Ising model at zero temperature

The exact determination of ground states of small systems is used in a scaling study of the random-field Ising model. While three variants of the model are found to be in the same universality class in 3 dimensions, the Gaussian and bimodal models behave distinctly in 4 dimensions with the latter apparently having a discontinuous jump in the magnetization. A finite-size scaling analysis is presented for this transition.

The water-enhanced Brazil nut effect

It is well known that a large dense intruder may rise to the surface of a vibrated granular bed, the Brazil nut effect. In this paper we describe a water-enhanced Brazil nut effect which occurs when the vibrated granular bed is fully immersed in a liquid. We use a bed of glass beads immersed in water and monitor the behaviour of a large steel intruder as the system is vibrated vertically. To aid our understanding, we have developed numerical simulations to model this system and provide detailed information on the fluid and grain motion. The mechanism responsible for the rapid rise of the intruder is shown to be fluid-enhanced ratcheting rather than simple differential drag.

Optimal paths and universality

Optimal paths in disordered systems are studied using two different models interpolating between weak and infinitely strong disorder. In one case, exact numerical methods are used to study the optimal path in a two-dimensional square lattice whereas a renormalization-group analysis is employed on hierarchical lattices in the other. The scaling behaviour is monitored as a function of parameters that tune the strength of the disorder. Two distinct scenarios are provided by the models: in the first, fractal behaviour occurs abruptly as soon as the disorder widens, while in the other it emerges as a limiting case of a self-affine regime.

Inelastic collapse of a randomly forced particle

We consider a randomly forced particle moving in a finite region, which rebounds inelastically with coefficient of restitution r on collision with the boundaries. We show that there is a transition at a critical value of r, r_c\equiv e^{-\pi/\sqrt{3}}, above which the dynamics is ergodic but beneath which the particle undergoes inelastic collapse, coming to rest after an infinite number of collisions in a finite time. The value of r_c is argued to be independent of the size of the region or the presence of a viscous damping term in the equation of motion.