Methodological Frontiers in Environmental Epidemiology

Environmental epidemiology comprises the epidemiologic study of those environmental factors that are outside the immediate control of the individual. Exposures of interest to environmental epidemiologists include air pollution, water pollution, occupational exposure to physical and chemical agents, as well as psychosocial elements of environmental concern. The main methodologic problem in environmental epidemiology is exposure assessment, a problem that extends through all of epidemiologic research but looms as a towering obstacle in environmental epidemiology. One of the most promising developments in improving exposure assessment in environmental epidemiology is to find exposure biomarkers, which could serve as built-in dosimeters that reflect the biologic footprint left behind by environmental exposures. Beyond exposure assessment, epidemiologists studying environmental exposures face the difficulty of studying small effects that may be distorted by confounding that eludes easy control. This challenge may prompt reliance on new study designs, such as two-stage designs in which exposure and disease information are collected in the first stage, and covariate information is collected on a subset of subjects in state two. While the analytic methods already available for environmental epidemiology are powerful, analytic methods for ecologic studies need further development. This workshop outlines the range of methodologic issues that environmental epidemiologists must address so that their work meets the goals set by scientists and society at large

Causation in the Presence of Weak Associations

none1siDespite their observational nature, epidemiologic studies have been used to make inductive inferences about the causes of human diseases. In this context, I mainly consider the term “cause” in its cognitive (explanatory) meaning, that is, by detecting causal factors and identifying mechanisms of diseases...openBoffetta, P.Boffetta, P

Three dimensional hysdrodynamic lattice-gas simulations of binary immiscible and ternary amphiphilic flow through porous media

We report the results of a study of multiphase flow in porous media. A Darcy's law for steady multiphase flow was investigated for both binary and ternary amphiphilic flow. Linear flux-forcing relationships satisfying Onsager reciprocity were shown to be a good approximation of the simulation data. The dependence of the relative permeability coefficients on water saturation was investigated and showed good qualitative agreement with experimental data. Non-steady state invasion flows were investigated, with particular interest in the asymptotic residual oil saturation. The addition of surfactant to the invasive fluid was shown to significantly reduce the residual oil saturation.Comment: To appear in Phys. Rev.

Feminism, Abortion and Disability: irreconcilable differences?

There has been considerable discussion of the political allegiance between the feminist and disability movements, but the question of abortion remains a thorny one. Disability rights advocates have been keen to demonstrate that it is possible to believe in a woman's right to sovereignty over the body and, yet, be opposed to the selective abortion of an impaired foetus – describing the latter as a form of 'weak' eugenics. The aim of this paper is to show that whilst there may be some points of agreement between the feminist and disability movements on the question of abortion, there exist fundamental and irreconcilable differences

Measures of gravitational entropy I. Self-similar spacetimes

We examine the possibility that the gravitational contribution to the entropy of a system can be identified with some measure of the Weyl curvature. In this paper we consider homothetically self-similar spacetimes. These are believed to play an important role in describing the asymptotic properties of more general models. By exploiting their symmetry properties we are able to impose significant restrictions on measures of the Weyl curvature which could reflect the gravitational entropy of a system. In particular, we are able to show, by way of a more general relation, that the most widely used "dimensionless" scalar is \textit{not} a candidate for this measure along homothetic trajectories.Comment: revtex, minor clarifications, to appear in Physical Review

Phase separation in an homogeneous shear flow: Morphology, growth laws and dynamic scaling

We investigate numerically the influence of an homogeneous shear flow on the spinodal decomposition of a binary mixture by solving the Cahn-Hilliard equation in a two-dimensional geometry. Several aspects of this much studied problem are clarified. Our numerical data show unambiguously that, in the shear flow, the domains have on average an elliptic shape. The time evolution of the three parameters describing this ellipse are obtained for a wide range of shear rates. For the lowest shear rates investigated, we find the growth laws for the two principal axis $R_\perp (t) \sim constant$, $R_\parallel(t) \sim t$, while the mean orientation of the domains with respect to the flow is inversely proportional to the strain. This implies that when hydrodynamics is neglected a shear flow does not stop the domain growth process. We investigate also the possibility of dynamic scaling, and show that only a non trivial form of scaling holds, as predicted by a recent analytical approach to the case of a non-conserved order parameter. We show that a simple physical argument may account for these results.Comment: Version accepted for publication - Physical Review

The association between first and second wave COVID-19 mortality in Italy

Background: The relation between the magnitude of successive waves of the COVID-19 outbreak within the same communities could be useful in predicting the scope of new outbreaks. Methods: We investigated the extent to which COVID-19 mortality in Italy during the second wave was related to first wave mortality within the same provinces. We compared data on province-specific COVID-19 2020 mortality in two time periods, corresponding to the first wave (February 24\u2013June 30, 2020) and to the second wave (September 1\u2013December 31, 2020), using cubic spline regression. Results: For provinces with the lowest crude mortality rate in the first wave (February\u2013June), i.e. < 22 cases/100,000/month, mortality in the second wave (September\u2013December) was positively associated with mortality during the first wave. In provinces with mortality greater than 22/100,000/month during the first wave, higher mortality in the first wave was associated with a lower second wave mortality. Results were similar when the analysis was censored at October 2020, before the implementation of region-specific measures against the outbreak. Neither vaccination nor variant spread had any role during the study period. Conclusions: These findings indicate that provinces with the most severe initial COVID-19 outbreaks, as assessed through mortality data, faced milder second waves

Symmetrical arrangement of proteins under release-ready vesicles in presynaptic terminals

Controlled release of neurotransmitters stored in synaptic vesicles (SVs) is a fundamental process that is central to all information processing in the brain. This relies on tight coupling of the SV fusion to action potential-evoked presynaptic Ca2+ influx. This Ca2+-evoked release occurs from a readily releasable pool (RRP) of SVs docked to the plasma membrane (PM). The protein components involved in initial SV docking/tethering and the subsequent priming reactions which make the SV release ready are known. Yet, the supramolecular architecture and sequence of molecular events underlying SV release are unclear. Here, we use cryoelectron tomography analysis in cultured hippocampal neurons to delineate the arrangement of the exocytosis machinery under docked SVs. Under native conditions, we find that vesicles are initially "tethered" to the PM by a variable number of protein densities (∼10 to 20 nm long) with no discernible organization. In contrast, we observe exactly six protein masses, each likely consisting of a single SNAREpin with its bound Synaptotagmins and Complexin, arranged symmetrically connecting the "primed" vesicles to the PM. Our data indicate that the fusion machinery is likely organized into a highly cooperative framework during the priming process which enables rapid SV fusion and neurotransmitter release following Ca2+ influx