The Tukey trend test: Multiplicity adjustment using multiple marginal models

In dose–response analysis, it is a challenge to choose appropriate linear or curvilinear shapes when considering multiple, differently scaled endpoints. It has been proposed to fit several marginal regression models that try sets of different transformations of the dose levels as explanatory variables for each endpoint. However, the multiple testing problem underlying this approach, involving correlated parameter estimates for the dose effect between and within endpoints, could only be adjusted heuristically. An asymptotic correction for multiple testing can be derived from the score functions of the marginal regression models. Based on a multivariate t-distribution, the correction provides a one-step adjustment of p-values that accounts for the correlation between estimates from different marginal models. The advantages of the proposed methodology are demonstrated through three example datasets, involving generalized linear models with differently scaled endpoints, differing covariates, and a mixed effect model and through simulation results. The methodology is implemented in an R package. © 2021 The Authors. Biometrics published by Wiley Periodicals LLC on behalf of International Biometric Society

The Resistive-Plate WELL with Argon mixtures - a robust gaseous radiation detector

A thin single-element THGEM-based, Resistive-Plate WELL (RPWELL) detector was operated with 150 GeV/c muon and pion beams in Ne/(5%CH$_4$), Ar/(5%CH$_4$) and Ar/(7%CO$_2$); signals were recorded with 1 cm$^2$ square pads and SRS/APV25 electronics. Detection efficiency values greater than 98% were reached in all the gas mixtures, at average pad multiplicity of 1.2. The use of the 10$^9${\Omega}cm resistive plate resulted in a completely discharge-free operation also in intense pion beams. The efficiency remained essentially constant at 98-99% up to fluxes of $\sim$10$^4$Hz/cm$^2$, dropping by a few % when approaching 10$^5$ Hz/cm$^2$. These results pave the way towards cost-effective, robust, efficient, large-scale detectors for a variety of applications in future particle, astro-particle and applied fields. A potential target application is digital hadron calorimetry.Comment: presented at the 2016 VIenna Conf. On instrumentation. Submitted to the Conference proceeding

The Interaction of Laser Energy with Ureter Tissues in a Long Term Investigation

This study investigates tissue responses after laser irradiation of the rabbit ureter, which serves as an experimental model for rectourogenital fistulae of children. Twenty-five rabbit ureters were irradiated intraluminally by a Nd:YAG laser 1320 nm (2 Watt, 20 seconds and 3 Watt, 8 seconds) via an applicator with radialsymmetrical light distribution. Immediately, 2 weeks, 4 weeks, 8 weeks, and 16 weeks after irradiation, the ureters were X-rayed with contrast solution and prepared for light and transmission electron microscopy. For the parameters employed, no apparent morphological differences could be observed. Immediately, the central laser zone showed a transmural therrnonecrosis prevailed by cellular destruction, condensed ground substance and occlusion of most vascular lumina. Peripheral laser zones displayed urothelial vacuolations. Between 2 and 16 weeks, urothelial regeneration and ingrowth of granulation tissue caused a luminal stenosis or occlusion followed by transformation into scar tissue. In some peripheral laser zones, a hydroureter with marked luminal dilatation developed. We conclude that the ureter is occluded if the expanding force of the growing scar tissue exceeds the hydrostatic pressure of the obstructed urine. A laser occlusion of rectourogenital fistulae will be easier to achieve since fistula occlusion does not entail an obstruction of the urine flow

Understanding Nonlinear Pulse Propagation in Liquid Strand-Based Photonic Bandgap Fibers

Ultrafast supercontinuum generation crucially depends on the dispersive properties of the underlying waveguide. This strong dependency allows for tailoring nonlinear frequency conversion and is particularly relevant in the context of waveguides that include geometry-induced resonances. Here, we experimentally uncovered the impact of the relative spectral distance between the pump and the bandgap edge on the supercontinuum generation and in particular on the dispersive wave formation on the example of a liquid strand-based photonic bandgap fiber. In contrast to its air-hole-based counterpart, a bandgap fiber shows a dispersion landscape that varies greatly with wavelength. Particularly due to the strong dispersion variation close to the bandgap edges, nanometer adjustments of the pump wavelength result in a dramatic change of the dispersive wave generation (wavelength and threshold). Phase-matching considerations confirm these observations, additionally revealing the relevance of third order dispersion for interband energy transfer. The present study provides additional insights into the nonlinear frequency conversion of resonance-enhanced waveguide systems which will be relevant for both understanding nonlinear processes as well as for tailoring the spectral output of nonlinear fiber sources

Numerical and Experimental Demonstration of Intermodal Dispersive Wave Generation

Abstract Evidence of intermodal dispersive wave generation mediated by intermodal cross‐phase modulation (iXPM) between different transverse modes during supercontinuum generation in silicon nitride waveguides is presented. The formation of a higher‐order soliton in one strong transverse mode leads to phase modulation of a second, weak transverse mode by iXPM. The phase modulation enables not only supercontinuum generation but also dispersive wave generation within the weak mode, that otherwise has insufficient power to facilitate dispersive wave formation. The nonlinear frequency conversion scheme presented here suggests phase‐matching conditions beyond what is currently known, which can be exploited for extending the spectral bandwidth within supercontinuum generation.Intermodal dispersive wave generation mediated by intermodal cross‐phase modulation between different transverse modes during supercontinuum generation in silicon nitride waveguides is demonstrated. The phase modulation enables dispersive wave generation within a weak mode, that otherwise has insufficient power to facilitate dispersive wave formation. This process suggests new phase‐matching conditions for frequency conversion beyond to what is currently known. imag

Evaluation of incidence rates in pre-clinical studies using a williams-type procedure

The analysis of dose-response relationships is a common problem in pre-clinical studies. For example, proportions such as mortality rates and histopathological findings are of particular interest in repeated toxicity studies. Commonly applied designs consist of an untreated control group and several, possibly unequally spaced, dosage groups. The Williams test can be formulated as a multiple contrast test and is a powerful option to evaluate such data. In this paper, we consider simultaneous inference for Williams-type multiple contrasts when the response variable is binomial and sample sizes are only moderate. Approximate simultaneous confidence limits can be constructed using the quantiles of a multivariate normal distribution taking the correlation into account. Alternatively, multiplicity-adjusted p-values can be calculated as well. A simulation study shows that a simple correction based on adding pseudo observations leads to acceptable performance for moderate sample sizes, such as 40 per group. In addition, the calculation of adjusted p-values and approximate power is presented. Finally, the proposed methods are applied to example data from two toxicological studiesthe methods are available in an R-package. © 2010 The Berkeley Electronic Press. All rights reserved