Meta-analyses and adaptive group sequential designs in the clinical development process

Meta-analyses and adaptive group sequential designs in the clinical development proces

Nonparametric Estimation of ROC Curves Based on Bayesian Models When the True Disease State is Unknown

Nonparametric Estimation of ROC Curves Based on Bayesian Models When the True Disease State is Unknow

Adaptive and non-adaptive group sequential tests

Adaptive and non-adaptive group sequential test

Flat branches and pressure amorphization

After summarizing the phenomenology of pressure amorphization (PA), we present a theory of PA based on the notion that one or more branches of the phonon spectrum soften and flatten with increasing pressure. The theory expresses the anharmonic dynamics of the flat branches in terms of local modes, represented by lattice Wannier functions, which are in turn used to construct an effective Hamiltonian. When the low-pressure structure becomes metastable with respect to the high-pressure equilibrium phase and the relevant branches are sufficiently flat, transformation into an amorphous phase is shown to be kinetically favored because of the exponentially large number of both amorphous phases and reaction pathways. In effect, the critical-size nucleus for the first-order phase transition is found to be reduced to a single unit cell, or nearly so. Random nucleation into symmetrically equivalent local configurations characteristic of the high-pressure structure is then shown to overwhelm any possible domain growth, and an ``amorphous'' structure results.Comment: 8 pages with 3 postscript figures embedded; Proceedings of the 4th International Discussion Meeting on Relaxations in Complex Systems, Hersonissos, Heraklion, Crete, June 16-23, ed. K. L. Ngai, Special Issues of the Journal of Non-Crystalline Solids, 200

Further insights into aspects of the EU illicit drugs market: summaries and key findings

This publication presents key findings and summaries of selected reports from the study ‘Further insights into aspects of the EU illicit drugs market’ (Trautmann, Kilmer and Turnbull, forthcoming 2013), which provides an analysis of characteristics and operations of the EU’s illicit drugs market, as called for by the European Commission. This study is a follow-up of the earlier European Commission study, which presented an analysis of the developments of the global illicit drug markets, the drug problems and drug policy responses in the period 1998-2007 (Reuter and Trautmann 2009). The discussions of that study resulted in a number of further research questions. Some of the questions considered most important by the European Commission have been put together in a call for a further analysis of the EU illicit drugs market and responses to it, focusing on a number of aspects in the following four areas: A. An analysis of specific characteristics, mechanisms and factors that govern the EU illicit drugs market, including a conceptual framework for thinking about the structure of drug suppliers in the EU, an assessment whether there have been significant shifts in how drugs are supplied in the EU and an assessment of the extent to which drug suppliers are involved in different drugs and other criminal activities. B. A detailed analysis of the size and share of the EU illicit drug market, providing an estimate of the volume of the ‘EU market’ in illicit drugs (production and trafficking), providing an estimate of the profits generated by this market, analysing whether the EU drugs market is more supply or demand driven and exploring various aspects of drug use: user types, availability and consumption estimates. C. A detailed analysis of a number of potential policy impacts on the EU drug market(s) in recent years, assessing the impact of opioid substitution treatment (OST) on the European heroin market and the impact of policy changes on two EU drug markets. D. Scanning the future – trends in the market and policy responses, exploring expert views on future key trends of the illicit drug markets and policy responses in the EU

Cell-Type-Specific Cytokinin Distribution within the Arabidopsis Primary Root Apex

Cytokinins (CKs) play a crucial role in many physiological and developmental processes at the levels of individual plant components (cells, tissues, and organs) and by coordinating activities across these parts. High-resolution measurements of intracellular CKs in different plant tissues can therefore provide insights into their metabolism and mode of action. Here, we applied fluorescence-activated cell sorting of green fluorescent protein (GFP)-marked cell types, combined with solid-phase microextraction and an ultra-high-sensitivity mass spectrometry (MS) method for analysis of CK biosynthesis and homeostasis at cellular resolution. This method was validated by series of control experiments, establishing that protoplast isolation and cell sorting procedures did not greatly alter endogenous CK levels. The MS-based method facilitated the quantification of all the well known CK isoprenoid metabolites in four different transgenic Arabidopsis thaliana lines expressing GFP in specific cell populations within the primary root apex. Our results revealed the presence of a CK gradient within the Arabidopsis root tip, with a concentration maximum in the lateral root cap, columella, columella initials, and quiescent center cells. This distribution, when compared with previously published auxin gradients, implies that the well known antagonistic interactions between the two hormone groups are cell type specific