Causal Inference When Counterfactuals Depend on the Proportion of All Subjects Exposed

The assumption that no subject's exposure affects another subject's outcome, known as the no-interference assumption, has long held a foundational position in the study of causal inference. However, this assumption may be violated in many settings, and in recent years has been relaxed considerably. Often this has been achieved with either the aid of a known underlying network, or the assumption that the population can be partitioned into separate groups, between which there is no interference, and within which each subject's outcome may be affected by all the other subjects in the group via the proportion exposed (the stratified interference assumption). In this paper, we instead consider a complete interference setting, in which each subject affects every other subject's outcome. In particular, we make the stratified interference assumption for a single group consisting of the entire sample. This can occur when the exposure is a shared resource whose efficacy is modified by the number of subjects among whom it is shared. We show that a targeted maximum likelihood estimator for the i.i.d.~setting can be used to estimate a class of causal parameters that includes direct effects and overall effects under certain interventions. This estimator remains doubly-robust, semiparametric efficient, and continues to allow for incorporation of machine learning under our model. We conduct a simulation study, and present results from a data application where we study the effect of a nurse-based triage system on the outcomes of patients receiving HIV care in Kenyan health clinics.Comment: 23 pages main article, 23 pages supplementary materials + references, 4 tables, 1 figur

Multi-dimensional parameter estimation of heavy-tailed moving averages

In this paper we present a parametric estimation method for certain multi-parameter heavy-tailed L\'evy-driven moving averages. The theory relies on recent multivariate central limit theorems obtained in [3] via Malliavin calculus on Poisson spaces. Our minimal contrast approach is related to the papers [14, 15], which propose to use the marginal empirical characteristic function to estimate the one-dimensional parameter of the kernel function and the stability index of the driving L\'evy motion. We extend their work to allow for a multi-parametric framework that in particular includes the important examples of the linear fractional stable motion, the stable Ornstein-Uhlenbeck process, certain CARMA(2, 1) models and Ornstein-Uhlenbeck processes with a periodic component among other models. We present both the consistency and the associated central limit theorem of the minimal contrast estimator. Furthermore, we demonstrate numerical analysis to uncover the finite sample performance of our method

Uniparental mitochondrial DNA inheritance is not affected in Ustilago maydis Δatg11 mutants blocked in mitophagy

Background: Maternal or uniparental inheritance (UPI) of mitochondria is generally observed in sexual eukaryotes, however, the underlying mechanisms are diverse and largely unknown. Recently, based on the use of mutants blocked in autophagy, it has been demonstrated that autophagy is required for strict maternal inheritance in the nematode Caenorhabditis elegans. Uniparental mitochondrial DNA (mtDNA) inheritance has been well documented for numerous fungal species, and in particular, has been shown to be genetically governed by the mating-type loci in the isogamous species Cryptococcus neoformans, Phycomyces blakesleeanus and Ustilago maydis. Previously, we have shown that the a2 mating-type locus gene lga2 is decisive for UPI during sexual development of U. maydis. In axenic culture, conditional overexpression of lga2 triggers efficient loss of mtDNA as well as mitophagy. To assess a functional relationship, we have investigated UPI in U. maydis Δatg11 mutants, which are blocked in mitophagy. Results: This study has revealed that Äatg11 mutants are not affected in pathogenic development and this has allowed us to analyse UPI under comparable developmental conditions between mating-compatible wild-type and mutant strain combinations. Explicitly, we have examined two independent strain combinations that gave rise to different efficiencies of UPI. We demonstrate that in both cases UPI is atg11-independent, providing evidence that mitophagy is not critical for UPI in U. maydis, even under conditions of strict UPI. Conclusions: Until now, analysis of a role of mitophagy in UPI has not been reported for microbial species. Our study suggests that selective autophagy does not contribute to UPI in U. maydis, but is rather a consequence of selective mtDNA elimination in response to mitochondrial damage. © 2015 Wagner-Vogel et al.; licensee BioMed Central

Spherical collapse of dark energy with an arbitrary sound speed

We consider a generic type of dark energy fluid, characterised by a constant equation of state parameter w and sound speed c_s, and investigate the impact of dark energy clustering on cosmic structure formation using the spherical collapse model. Along the way, we also discuss in detail the evolution of dark energy perturbations in the linear regime. We find that the introduction of a finite sound speed into the picture necessarily induces a scale-dependence in the dark energy clustering, which in turn affects the dynamics of the spherical collapse in a scale-dependent way. As with other, more conventional fluids, we can define a Jeans scale for the dark energy clustering, and hence a Jeans mass M_J for the dark matter which feels the effect of dark energy clustering via gravitational interactions. For bound objects (halos) with masses M >> M_J, the effect of dark energy clustering is maximal. For those with M << M_J, the dark energy component is effectively homogeneous, and its role in the formation of these structures is reduced to its effects on the Hubble expansion rate. To compute quantitatively the virial density and the linearly extrapolated threshold density, we use a quasi-linear approach which is expected to be valid up to around the Jeans mass. We find an interesting dependence of these quantities on the halo mass M, given some w and c_s. The dependence is the strongest for masses lying in the vicinity of M ~ M_J. Observing this M-dependence will be a tell-tale sign that dark energy is dynamic, and a great leap towards pinning down its clustering properties.Comment: 25 pages, 6 figures, matches version published in JCA

Modelling radiation-induced cell cycle delays

Ionizing radiation is known to delay the cell cycle progression. In particular after particle exposure significant delays have been observed and it has been shown that the extent of delay affects the expression of damage such as chromosome aberrations. Thus, to predict how cells respond to ionizing radiation and to derive reliable estimates of radiation risks, information about radiation-induced cell cycle perturbations is required. In the present study we describe and apply a method for retrieval of information about the time-course of all cell cycle phases from experimental data on the mitotic index only. We study the progression of mammalian cells through the cell cycle after exposure. The analysis reveals a prolonged block of damaged cells in the G2 phase. Furthermore, by performing an error analysis on simulated data valuable information for the design of experimental studies has been obtained. The analysis showed that the number of cells analyzed in an experimental sample should be at least 100 to obtain a relative error less than 20%.Comment: 19 pages, 11 figures, accepted for publication in Radiation and Environmental Biophysic

The etiology and prevention of feeding intolerance paralytic ileus – revisiting an old concept

Gastro-intestinal (G-I) motility is impaired ("paralytic ileus") after abdominal surgery. Premature feeding attempts delay recovery by inducing "feeding intolerance," especially abdominal distention that compromises respiration. Controlled studies (e.g., from Sloan-Kettering Memorial Hospital) have lead to recommendations that patients not be fed soon after major abdominal surgery to avoid this complication