SGLT-2 Inhibitors: A Novel Mechanism in Targeting Glycemic Control in Type 2 Diabetes Mellitus

OBJECTIVE: To review the chemistry, pharmacology, pharmacodynamics, pharmacokinetics, clinical efficacy, tolerability, dosing, drug interactions, and administration of canagliflozin, dapagliflozin, and empagliflozin, and comparing the benefit and risk aspects of using these agents in the older adult diabetes patient population. DATA SOURCES, STUDY SELECTION, DATA EXTRACTION, AND DATA SYNTHESIS: A search of PubMed using the terms SGLT-2 inhibitors, canagliflozin, dapagliflozin, empagliflozin, efficacy, and tolerability was performed to find relevant primary literature on each of the sodium/glucose cotransporter 2 (SGLT-2) inhibitors currently approved for use in type 2 diabetes. Phase III trials for all agents were included. All English-language articles from 2010 to 2015 appearing in these searches were reviewed for relevance to this paper. In addition, related articles suggested in the PubMed search were also reviewed. The SGLT-2 inhibitors have shown a reduction in hemoglobin A1c values and fasting plasma glucose levels with a low incidence of hypoglycemia. The incidence of mycotic infections is increased in patients taking an SGLT-2 inhibitor. CONCLUSION: SGLT-2 inhibitors may be a viable treatment option for patients not controlled on other oral agents. The risk of hypoglycemia is small. However, the clinical efficacy and tolerability of these agents has not been fully elucidated in older and frail patients

Monte Carlo simulations of copolymers at homopolymer interfaces: Interfacial structure as a function of the copolymer density

By means of extensive Monte Carlo simulations of the bond fluctuation model, we study the effect of adding AB diblock copolymers on the properties of an interface between demixed homopolymer phases. The parameters are chosen such that the homopolymers are strongly segregated, and the whole range of copolymer concentrations in the two phase coexistence region is scanned. We compare the ``mushroom'' regime, in which copolymers are diluted and do not interact with each other, with the ``wet brush'' regime, where copolymers overlap and stretch, but are still swollen by the homopolymers. A ``dry brush'' regime is never entered for our choice of chain lengths. ``Intrinsic'' profiles are calculated using a block analysis method introduced by us in earlier work. We discuss density profiles, orientational profiles and contact number profiles. In general, the features of the profiles are similar at all copolymer concentrations, however, the profiles in the concentrated regime are much broader than in the dilute regime. The results compare well with self-consistent field calculations.Comment: to appear in J. Chem. Phy

Effect of long range forces on the interfacial profiles in thin binary polymer films

We study the effect of surface fields on the interfacial properties of a binary polymer melt confined between two parallel walls. Each wall attracts a different component of the blend by a non-retarded van der Waals potential. An interface which runs parallel to the surfaces is stabilized in the center of the film. Using extensive Monte Carlo simulations we study the interfacial properties as a function of the film thickness, the strength of the surface forces and the lateral size over which the profiles across the film are averaged. We find evidence for capillary wave broadening of the apparent interfacial profiles. However, the apparent interfacial width cannot be described quantitatively by a simple logarithmic dependence on the film thickness. The Monte Carlo simulations reveal that the surface fields give rise to an additional reduction of the intrinsic interfacial width and an increase of the effective interfacial tension upon decreasing the film thickness. These modifications of the intrinsic interfacial properties are confirmed by self-consistent field calculations. Taking account of the thickness dependence of the intrinsic interfacial properties and the capillary wave broadening, we can describe our simulation results quantitatively.Comment: to appear in J.Chem.Phy

Measurement uncertainty relations

Measurement uncertainty relations are quantitative bounds on the errors in an approximate joint measurement of two observables. They can be seen as a generalization of the error/disturbance tradeoff first discussed heuristically by Heisenberg. Here we prove such relations for the case of two canonically conjugate observables like position and momentum, and establish a close connection with the more familiar preparation uncertainty relations constraining the sharpness of the distributions of the two observables in the same state. Both sets of relations are generalized to means of order $\alpha$ rather than the usual quadratic means, and we show that the optimal constants are the same for preparation and for measurement uncertainty. The constants are determined numerically and compared with some bounds in the literature. In both cases the near-saturation of the inequalities entails that the state (resp. observable) is uniformly close to a minimizing one.Comment: This version 2 contains minor corrections and reformulation

Validation, persuasion and recycling: capitalizing on the social ecology of newspaper use.

Journal ArticleTwo experiments used clinical validation to increase scrutiny of messages posted in public settings. The first experiment used a 2 (validation: no/yes) × 2 (persuasion: none/"it is important") factorial design to develop messages about newspaper recycling. The prompt (no validation/no persuasion) had little impact on newspaper recycling, but the other 3 signs all resulted in increased recycling while the signs were in place. After signs were removed, recycling remained significantly higher than baseline (marginally significant for validation/persuasion). At the end of the study, number of cognitions favoring recycling was significantly higher in the validation-only condition and was lower in the validation/persuasion condition. Experiment 2 tested whether signs would have more impact if they were sensitive to the social ecology of newspaper recycling; that is, readers' tendency to leave newspapers behind so others may read them. Messages based on a 2 (message: validation-only/validation plus persuasion) × 2 (ecology: no social ecology/social ecology) factorial design supported social ecology's importance. Furthermore, because of the increased sharing in the social ecology conditions, total numbers of newspapers used was significantly lower in those buildings. Validation only yielded sustained behavior change in both Experiments 1 and 2, supporting additional research on the question of whether validation can, by itself, lead to cognitive elaboration and self-persuasion. [ABSTRACT FROM AUTHOR

All-age hospitalization rates in coal seam gas areas in Queensland, Australia, 1995–2011

Background: Unconventional natural gas development (UNGD) is expanding globally, with Australia expanding development in the form of coal seam gas (CSG). Residents and other interest groups have voiced concerns about the potential environmental and health impacts related to CSG. This paper compares objective health outcomes from three study areas in Queensland, Australia to examine potential environmentally-related health impacts. Methods: Three study areas were selected in an ecologic study design: A CSG area, a coal mining area, and a rural/agricultural area. Admitted patient data, as well as population data and additional factors, were obtained for each calendar year from 1995 through 2011 to calculate all-age hospitalization rates and age-standardized rates in each of these areas. The three areas were compared using negative binomial regression analyses (unadjusted and adjusted models) to examine increases over time of hospitalization rates grouped by primary diagnosis (19 ICD chapters), with rate ratios serving to compare the within-area regression slopes between the areas. Results: The CSG area did not have significant increases in all-cause hospitalization rates over time for all-ages compared to the coal and rural study areas in adjusted models (RR: 1.02, 95 % CI: 1.00-1.04 as compared to the coal mining area; RR: 1.01, 95 % CI: 0.99-1.04 as compared to the rural area). While the CSG area did not show significant increases in specific hospitalization rates compared to both the coal mining and rural areas for any ICD chapters in the adjusted models, the CSG area showed increases in hospitalization rates compared only to the rural area for neoplasms (RR: 1.09, 95 % CI: 1.02-1.16) and blood/immune diseases (RR: 1.14, 95 % CI: 1.02-1.27). Conclusions: This exploratory study of all-age hospitalization rates for three study areas in Queensland suggests that certain hospital admissions rates increased more quickly in the CSG study area than in other study areas, particularly the rural area, after adjusting for key sociodemographic factors. These findings are an important first step in identifying potential health impacts of CSG in the Australian context and serve to generate hypotheses for future studies

Precursors of Cytochrome Oxidase in Cytochrome-Oxidase-Deficient Cells of Neurospora crassa

Three different cell types of Neurospora crassa deficient in cytochrome oxidase were studied: the nuclear mutant cni-1, the cytoplasmic mutant mi-1 and copper-depleted wild-type cells. * 1. The enzyme-deficient cells have retained a functioning mitochondrial protein synthesis. It accounted for 12–16% of the total protein synthesis of the cell. However, the analysis of mitochondrial translation products by gel electrophoresis revealed that different amounts of individual membrane proteins were synthesized. Especially mutant cni-1 produced large amounts of a small molecular weight translation product, which is barely detectable in wild-type. * 2. Mitochondrial preparations of cytochrome-oxidase-deficient cells were examined for precursors of cytochrome oxidase. The presence of polypeptide components of cytochrome oxidase in the mitochondria was established with specific antibodies. On the other hand, no significant amounts of heme a could be extracted. * 3. Radioactively labelled components of cytochrome oxidase were isolated by immunoprecipitation and analysed by gel electrophoresis. All three cell types contained the enzyme components 4–7, which are translated on cytoplasmic ribosomes. The mitochondrially synthesized components 1–3 were present in mi-1 mutant and in copper-depleted wild-type cells. In contrast, components 2 and 3 were not detectable in the nuclear mutant cni-1. Both relative and absolute amounts of these polypeptides in the enzyme-deficient cells were quite different from those in wild-type cells. * 4. The components of cytochrome oxidase found in the enzyme-deficient cells were tightly associated with the mitochondrial membranes. * 5. Processes, which affect and may control the production of enzyme precursors or their assembly to a functional cytochrome oxidase are discussed