Multi-step Richardson-Romberg Extrapolation: Remarks on Variance Control and complexity

We propose a multi-step Richardson-Romberg extrapolation method for the computation of expectations $E f(X_{_T})$ of a diffusion $(X_t)_{t\in [0,T]}$ when the weak time discretization error induced by the Euler scheme admits an expansion at an order $R\ge 2$. The complexity of the estimator grows as $R^2$ (instead of $2^R$) and its variance is asymptotically controlled by considering some consistent Brownian increments in the underlying Euler schemes. Some Monte carlo simulations carried with path-dependent options (lookback, barriers) which support the conjecture that their weak time discretization error also admits an expansion (in a different scale). Then an appropriate Richardson-Romberg extrapolation seems to outperform the Euler scheme with Brownian bridge.Comment: 28 pages, \`a para\^itre dans Monte Carlo Methods and Applications Journa

Long-Distance Wind-Dispersal of Spores in a Fungal Plant Pathogen: Estimation of Anisotropic Dispersal Kernels from an Extensive Field Experiment

Given its biological significance, determining the dispersal kernel (i.e., the distribution of dispersal distances) of spore-producing pathogens is essential. Here, we report two field experiments designed to measure disease gradients caused by sexually- and asexually-produced spores of the wind-dispersed banana plant fungus Mycosphaerella fijiensis. Gradients were measured during a single generation and over 272 traps installed up to 1000 m along eight directions radiating from a traceable source of inoculum composed of fungicide-resistant strains. We adjusted several kernels differing in the shape of their tail and tested for two types of anisotropy. Contrasting dispersal kernels were observed between the two types of spores. For sexual spores (ascospores), we characterized both a steep gradient in the first few metres in all directions and rare long-distance dispersal (LDD) events up to 1000 m from the source in two directions. A heavy-tailed kernel best fitted the disease gradient. Although ascospores distributed evenly in all directions, average dispersal distance was greater in two different directions without obvious correlation with wind patterns. For asexual spores (conidia), few dispersal events occurred outside of the source plot. A gradient up to 12.5 m from the source was observed in one direction only. Accordingly, a thin-tailed kernel best fitted the disease gradient, and anisotropy in both density and distance was correlated with averaged daily wind gust. We discuss the validity of our results as well as their implications in terms of disease diffusion and management strategy

Nota editorial: alejandro prospero reverend (el médico del libertador)

Si el nombre de Alejandro Próspero Révérend, no ha sido olvidado en la América Latina" como probablemente sí lo está en Francia, lugar de su nacimiento, es porque el azar de su destino lo condujo a jugar un papel histórico con ocasión de la muerte de Simón Bolívar, Libertador del Continente Suramericano. No hay libro de historia ni biografía, que no relate con gratitud los actos de consagración, de este médico francés y no alaben la filantropía y la abnegación - nosotros diremos más simplemente, la conciencia y la probidad profesionales-con las cuales él cumplió la triste tarea que le impusieron las circunstancias

Quantification of the performance of chaotic micromixers on the basis of finite time Lyapunov exponents

Chaotic micromixers such as the staggered herringbone mixer developed by Stroock et al. allow efficient mixing of fluids even at low Reynolds number by repeated stretching and folding of the fluid interfaces. The ability of the fluid to mix well depends on the rate at which "chaotic advection" occurs in the mixer. An optimization of mixer geometries is a non trivial task which is often performed by time consuming and expensive trial and error experiments. In this paper an algorithm is presented that applies the concept of finite-time Lyapunov exponents to obtain a quantitative measure of the chaotic advection of the flow and hence the performance of micromixers. By performing lattice Boltzmann simulations of the flow inside a mixer geometry, introducing massless and non-interacting tracer particles and following their trajectories the finite time Lyapunov exponents can be calculated. The applicability of the method is demonstrated by a comparison of the improved geometrical structure of the staggered herringbone mixer with available literature data.Comment: 9 pages, 8 figure

Finite one dimensional impenetrable Bose systems: Occupation numbers

Bosons in the form of ultra cold alkali atoms can be confined to a one dimensional (1d) domain by the use of harmonic traps. This motivates the study of the ground state occupations $\lambda_i$ of effective single particle states $\phi_i$, in the theoretical 1d impenetrable Bose gas. Both the system on a circle and the harmonically trapped system are considered. The $\lambda_i$ and $\phi_i$ are the eigenvalues and eigenfunctions respectively of the one body density matrix. We present a detailed numerical and analytic study of this problem. Our main results are the explicit scaled forms of the density matrices, from which it is deduced that for fixed $i$ the occupations $\lambda_i$ are asymptotically proportional to $\sqrt{N}$ in both the circular and harmonically trapped cases.Comment: 22 pages, 8 figures (.eps), uses REVTeX

Salvage for cervical recurrences of head and neck cancer with dissection and interstitial high dose rate brachytherapy

Salvage therapy in head and neck cancer (HNC) is a controversy issue and the literature is scarce regarding the use of interstitial high-dose rate brachytherapy (I-HDR) in HNC. We evaluated the long-term results of a treatment policy combining salvage surgery and I-HDR for cervical recurrences of HNC. Charts of 21 patients treated from 1994 to 2004 were reviewed. The crude local control rate for all patients was 52.4%. The 5- and 8-years overall (OS) and local relapse-free survival (LRFS) rates were 50%, 42.9%, 42.5% and 28.6%, respectively. The only predictive factor associated to LFRS and OS was negative margin status (p = 0.0007 and p = 0.0002). We conclude that complete surgery is mandatory for long term control and the doses given by brachytherapy are not high enough to compensate for microscopic residual disease after surgery

Optimization of chaotic micromixers using finite time Lyapunov exponents

In microfluidics mixing of different fluids is a highly non-trivial task due to the absence of turbulence. The dominant process allowing mixing at low Reynolds number is therefore diffusion, thus rendering mixing in plain channels very inefficient. Recently, passive chaotic micromixers such as the staggered herringbone mixer were developed, allowing efficient mixing of fluids by repeated stretching and folding of the fluid interfaces. The optimization of the geometrical parameters of such mixer devices is often performed by time consuming and expensive trial and error experiments. We demonstrate that the application of the lattice Boltzmann method to fluid flow in highly complex mixer geometries together with standard techniques from statistical physics and dynamical systems theory can lead to a highly efficient way to optimize micromixer geometries. The strategy applies massively parallel fluid flow simulations inside a mixer, where massless and noninteracting tracer particles are introduced. By following their trajectories we can calculate finite time Lyapunov exponents in order to quantify the degree of chaotic advection inside the mixer. The current report provides a review of our results published in [1] together with additional details on the simulation methodology

Potentially inappropriate medication use among patients with Alzheimer disease in the REAL.FR cohort: be aware of atropinic and benzodiazepine drugs!

Abstract Objective Few studies have investigated potentially inappropriate medication (PIM) use in patients with Alzheimer's disease (AD). The aim of our study was to assess the prevalence of PIM in community-dwelling patients diagnosed with mild-to-moderate AD and identify the clinical factors associated with PIM prescriptions. Methods REAL.FR is a 4-year, prospective, multicenter French cohort of AD patients recruited in centers of expertise. We analyzed patient baseline data at entry into the study. PIMs were assessed using the Laroche list. A multivariate logistic regression was conducted to assess factors associated with PIMs. Results A total of 684 AD patients were enrolled in the study [mean age 77.9±6.8 years, 486 (71.0 %) females]. According to the Laroche list, 46.8 % [95 % confidence interval (CI) 43.0-50.5 %] of the patients had at least one PIM. "Cerebral vasodilators" were the most widely used class of PIM, accounting for 24.0 % (95 % CI 20.9-27.3 %) of all prescriptions, followed by atropinic drugs (17.0 %, 95 % CI 14.1-19.8 %) and long half-life benzodiazepines (8.5 %, 95 % CI 6.4-10.6 %). Atropinic drugs were associated with cholinesterase inhibitors in 16 % of patients. In the multivariate analysis, only two factors, namely, female gender [odds ratio (OR) 1.5, 95 % CI 1.1-2.2] and polypharmacy (≥5 drugs; OR3.6, 95 % CI 2.6-4.5) were associated with prescriptions for PIMs. Conclusions These results reveal that approximately one out of two community-dwelling patients with mild-to-moderate AD treated by AD specialists use PIMs. They also indicate that the characteristics of the disease and the pharmacodynamic/ pharmacokinetic profile of the drugs prescribed are not sufficiently taken into account by physicians when prescribing for AD patients

Pharmacogenomics of statin-related myopathy:Meta-analysis of rare variants from whole-exome sequencing

AIMS:Statin-related myopathy (SRM), which includes rhabdomyolysis, is an uncommon but important adverse drug reaction because the number of people prescribed statins world-wide is large. Previous association studies of common genetic variants have had limited success in identifying a genetic basis for this adverse drug reaction. We conducted a multi-site whole-exome sequencing study to investigate whether rare coding variants confer an increased risk of SRM. METHODS AND RESULTS:SRM 3-5 cases (N = 505) and statin treatment-tolerant controls (N = 2047) were recruited from multiple sites in North America and Europe. SRM 3-5 was defined as symptoms consistent with muscle injury and an elevated creatine phosphokinase level >4 times upper limit of normal without another likely cause of muscle injury. Whole-exome sequencing and variant calling was coordinated from two analysis centres, and results of single-variant and gene-based burden tests were meta-analysed. No genome-wide significant associations were identified. Given the large number of cases, we had 80% power to identify a variant with minor allele frequency of 0.01 that increases the risk of SRM 6-fold at genome-wide significance. CONCLUSIONS:In this large whole-exome sequencing study of severe statin-related muscle injury conducted to date, we did not find evidence that rare coding variants are responsible for this adverse drug reaction. Larger sample sizes would be required to identify rare variants with small effects, but it is unclear whether such findings would be clinically actionable