Systematic review of SGLT2 receptor inhibitors in dual or triple therapy in type 2 diabetes

Background Despite the number of medications for type 2 diabetes, many people with the condition do not achieve good glycaemic control. Some existing glucose-lowering agents have adverse effects such as weight gain or hypoglycaemia. Type 2 diabetes tends to be a progressive disease, and most patients require treatment with combinations of glucose-lowering agents. The sodium glucose co-transporter 2 (SGLT2) receptor inhibitors are a new class of glucose-lowering agents. Objective To assess the clinical effectiveness and safety of the SGLT2 receptor inhibitors in dual or triple therapy in type 2 diabetes. Data sources MEDLINE, Embase, Cochrane Library (all sections); Science Citation Index; trial registries; conference abstracts; drug regulatory authorities; bibliographies of retrieved papers. Inclusion criteria Randomised controlled trials of SGLT2 receptor inhibitors compared with placebo or active comparator in type 2 diabetes in dual or combination therapy. Methods Systematic review. Quality assessment used the Cochrane risk of bias score. Results Seven trials, published in full, assessed dapagliflozin and one assessed canagliflozin. Trial quality appeared good. Dapagliflozin 10 mg reduced HbA1c by −0.54% (weighted mean differences (WMD), 95% CI −0.67 to −0.40) compared to placebo, but there was no difference compared to glipizide. Canagliflozin reduced HbA1c slightly more than sitagliptin (up to −0.21% vs sitagliptin). Both dapagliflozin and canagliflozin led to weight loss (dapagliflozin WMD −1.81 kg (95% CI −2.04 to −1.57), canagliflozin up to −2.3 kg compared to placebo). Limitations Long-term trial extensions suggested that effects were maintained over time. Data on canagliflozin are currently available from only one paper. Costs of the drugs are not known so cost-effectiveness cannot be assessed. More data on safety are needed, with the Food and Drug Administration having concerns about breast and bladder cancers. Conclusions Dapagliflozin appears effective in reducing HbA1c and weight in type 2 diabetes, although more safety data are needed

The self-organized critical forest-fire model on large scales

We discuss the scaling behavior of the self-organized critical forest-fire model on large length scales. As indicated in earlier publications, the forest-fire model does not show conventional critical scaling, but has two qualitatively different types of fires that superimpose to give the effective exponents typically measured in simulations. We show that this explains not only why the exponent characterizing the fire-size distribution changes with increasing correlation length, but allows also to predict its asymptotic value. We support our arguments by computer simulations of a coarse-grained model, by scaling arguments and by analyzing states that are created artificially by superimposing the two types of fires.Comment: 26 pages, 7 figure

Phase Transitions in a Forest-Fire Model

We investigate a forest-fire model with the density of empty sites as control parameter. The model exhibits three phases, separated by one first-order phase transition and one 'mixed' phase transition which shows critical behavior on only one side and hysteresis. The critical behavior is found to be that of the self-organized critical forest-fire model [B. Drossel and F. Schwabl, Phys. Rev. Lett. 69, 1629 (1992)], whereas in the adjacent phase one finds the spiral waves of the Bak et al. forest-fire model [P. Bak, K. Chen and C. Tang, Phys. Lett. A 147, 297 (1990)]. In the third phase one observes clustering of trees with the fire burning at the edges of the clusters. The relation between the density distribution in the spiral state and the percolation threshold is explained and the implications for stationary states with spiral waves in arbitrary excitable systems are discussed. Furthermore, we comment on the possibility of mapping self-organized critical systems onto 'ordinary' critical systems.Comment: 30 pages RevTeX, 9 PostScript figures (Figs. 1,2,4 are of reduced quality), to appear in Phys. Rev.

Universal Behavior of the Coefficients of the Continuous Equation in Competitive Growth Models

The competitive growth models involving only one kind of particles (CGM), are a mixture of two processes one with probability $p$ and the other with probability $1-p$. The $p-$dependance produce crossovers between two different regimes. We demonstrate that the coefficients of the continuous equation, describing their universality classes, are quadratic in $p$ (or $1-p$). We show that the origin of such dependance is the existence of two different average time rates. Thus, the quadratic $p-$dependance is an universal behavior of all the CGM. We derive analytically the continuous equations for two CGM, in 1+1 dimensions, from the microscopic rules using a regularization procedure. We propose generalized scalings that reproduce the scaling behavior in each regime. In order to verify the analytic results and the scalings, we perform numerical integrations of the derived analytical equations. The results are in excellent agreement with those of the microscopic CGM presented here and with the proposed scalings.Comment: 9 pages, 3 figure

Corrections to scaling in the forest-fire model

We present a systematic study of corrections to scaling in the self-organized critical forest-fire model. The analysis of the steady-state condition for the density of trees allows us to pinpoint the presence of these corrections, which take the form of subdominant exponents modifying the standard finite-size scaling form. Applying an extended version of the moment analysis technique, we find the scaling region of the model and compute the first non-trivial corrections to scaling.Comment: RevTeX, 7 pages, 7 eps figure

A large-scale correlated study of linear optical absorption and low-lying excited states of polyacenes: Pariser-Parr-Pople Hamiltonian

In this paper we present large-scale correlated calculations of linear optical absorption spectrum of oligo-acenes containing up to seven benzene rings. For the calculations we used the Pariser-Parr-Pople (P-P-P) Hamiltonian, along with the configuration interaction (CI) technique at various levels such as the full CI (FCI), the quadruple CI (QCI) and multi-reference singles-doubles CI (MRSDCI). The role of Coulomb parameters used in the P-P-P Hamiltonian was examined by considering standard Ohno parameters, as well as a screened set of parameters. A detailed analysis of the many-body character of the important excited states contributing to the linear absorption has also been performed. The results of our calculations have been compared extensively with the theoretical work of other authors, as well as with the experiments.Comment: 45 pages, 9 figure

Forest fires and other examples of self-organized criticality

We review the properties of the self-organized critical (SOC) forest-fire model. The paradigm of self-organized criticality refers to the tendency of certain large dissipative systems to drive themselves into a critical state independent of the initial conditions and without fine-tuning of the parameters. After an introduction, we define the rules of the model and discuss various large-scale structures which may appear in this system. The origin of the critical behavior is explained, critical exponents are introduced, and scaling relations between the exponents are derived. Results of computer simulations and analytical calculations are summarized. The existence of an upper critical dimension and the universality of the critical behavior under changes of lattice symmetry or the introduction of immunity are discussed. A survey of interesting modifications of the forest-fire model is given. Finally, several other important SOC models are briefly described.Comment: 37 pages RevTeX, 13 PostScript figures (Figs 1, 4, 13 are of reduced quality to keep download times small