The effect of mirabegron on patient-related outcomes in patients with overactive bladder: the results of post hoc correlation and responder analyses using pooled data from three randomized Phase III trials

Purpose To understand how improvements in the symptoms of overactive bladder (OAB) seen with the b3-adrenoceptor agonist mirabegron 50 mg, correlate with patient experience as measured by validated and standard patient-reported outcomes (PROs), and to identify whether there is overall directional consistency in the responsiveness of PROs to treatment effect. Methods In a post hoc analysis of pooled data from three randomized, double-blind, placebo-controlled, 12-week Phase III trials of mirabegron 50 mg once daily, responder rates for incontinence frequency (C50 % reduction in incontinence episodes/24 h from baseline to final visit), micturition frequency (B8 micturitions/24 h at final visit), and PROs [minimally important differences in patient perception of bladder condition (PPBC) and subsets of the overactive bladder questionnaire (OAB-q) measuring total health-related quality of life (HRQoL), and symptom bother] were evaluated individually and in combination. Results Mirabegron 50 mg demonstrated greater improvement from baseline to final visit than placebo for each of the responder analyses, whether for individual objective and subjective outcomes or combinations thereof. These improvements versus placebo were statistically significant for all double and triple responder analyses and for all single responder analyses except PPBC. PRO measurements showed directional consistency and significant correlations, and there were also significant correlations between objective and subjective measures of efficacy. Conclusions The improvements in objective measures seen with mirabegron 50 mg translate into a meaningful clinical benefit as evident by the directional consistency seen in HRQoL measures of benefit

Temperature Effects in the Composition of Metal Halide Perovskite thin Films

Metal halide perovskites have shown to be a structure with great promise as an efficient photovoltaic, but at the same time it is affected by instability problems that degrade their performance. Degradation mechanisms vary with temperature, moisture, oxidation, and energy conversion during light exposure. We study performance loss due to temperature by probing diffusion of elemental composition across the thickness of films produced by spin coating and for temperatures ranging from 20 to 200°C. X-ray reflectivity was used to identify the electron density, composition, and quality of the films, aided with X-ray fluorescence and X-ray photoelectron spectroscopy studies to obtain information about degradation of the organic phase of the films

Regulation of glycine metabolism by the glycine cleavage system and conjugation pathway in mouse models of Non-Ketotic Hyperglycinemia

Glycine abundance is modulated in a tissue-specific manner by use in biosynthetic reactions, catabolism by the glycine cleavage system (GCS) and excretion via glycine conjugation. Dysregulation of glycine metabolism is associated with multiple disorders including epilepsy, developmental delay and birth defects. Mutation of the GCS component glycine decarboxylase (GLDC) in Non-Ketotic Hyperglycinemia (NKH) causes accumulation of glycine in body fluids, but there is a gap in our knowledge regarding the effects on glycine metabolism in tissues. Here, we analysed mice carrying mutations in Gldc that result in severe or mild elevations of plasma glycine and model NKH. Liver of Gldc-deficient mice accumulated glycine and numerous glycine derivatives, including multiple acylglycines, indicating increased flux through reactions mediated by enzymes including glycine-N-acyltransferase and arginine:glycine amidinotransferase. Levels of dysregulated metabolites increased with age and were normalised by liver-specific rescue of Gldc expression. Brain tissue exhibited increased abundance of glycine, as well as derivatives including guanidinoacetate, which may itself be epileptogenic. Elevation of brain tissue glycine occurred even in the presence of only mildly elevated plasma glycine in mice carrying a missense allele of Gldc. Treatment with benzoate enhanced hepatic glycine conjugation thereby lowering plasma and tissue glycine. Moreover, administration of a glycine conjugation pathway intermediate, cinnamate, similarly achieved normalisation of liver glycine derivatives and circulating glycine. Although exogenous benzoate and cinnamate impact glycine levels via activity of glycine-N-acyltransferase, that is not expressed in brain, they are sufficient to lower levels of glycine and derivatives in brain tissue of treated Gldc-deficient mice

Bounded solutions of fermions in the background of mixed vector-scalar P\"{o}schl-Teller-like potentials

The problem of a fermion subject to a convenient mixing of vector and scalar potentials in a two-dimensional space-time is mapped into a Sturm-Liouville problem. For a specific case which gives rise to an exactly solvable effective modified P\"{o}schl-Teller potential in the Sturm-Liouville problem, bound-state solutions are found. The behaviour of the upper and lower components of the Dirac spinor is discussed in detail and some unusual results are revealed. The Dirac delta potential as a limit of the modified P% \"{o}schl-Teller potential is also discussed. The problem is also shown to be mapped into that of massless fermions subject to classical topological scalar and pseudoscalar potentials.Comment: 10 pages, 1 figur

Electronic Developments for the Hades RPC Wall: Overview and Progress

This contribution presents the current status and progress of the electronics developed for the Resistive Plate Chamber detector of HADES. This new detector for the time-of-flight detection system will contain more than 1000 RPC modules, covering a total active area of around 7 m2. The Front-End electronics consist of custom-made boards that exploit the benefit of the use of commercial components to achieve time resolutions below 100 ps. The Readout electronics, also custom-made, is a multipurpose board providing a 128- channel Time to Digital Converter (TDC) based on the HPTDC chip

Lepton Flavor Violation in the Two Higgs Doublet Model type III

We consider the Two Higgs Doublet Model (2HDM) of type III which leads to Flavour Changing Neutral Currents (FCNC) at tree level in the leptonic sector. In the framework of this model we can have, in principle, two situations: the case (a) when both doublets acquire a vacuum expectation value different from zero and the case (b) when only one of them is not zero. In addition, we show that we can make two types of rotations for the flavor mixing matrices which generates four types of lagrangians, with the rotation of type I we recover the case (b) from the case (a) in the limit $\tan \beta \to \infty$, and with the rotation of type II we obtain the case (b) from (a) in the limit $\tan \beta \to 0.$Moreover, two of the four possible lagrangians correspond to the models of types I and II plus Flavor Changing (FC) interactions. The analitical expressions of the partial lepton number violating widths $\Gamma (\mu \to eee)$ and $\Gamma (\mu \to e\gamma)$are derived for the cases (a) and (b) and both types of rotations.$$In all cases these widths go asymptotically to zero in the decoupling limit for all Higgses. We present from our analysis upper bounds for the flavour changing transition $\mu \to e,$ and we show that such bounds are sensitive to the VEV structure and the type of rotation utilized.Comment: 7 pages RevTeX4, 4 figures postscript, new section added and some new reference

Interlayer-confined Cu(II) complex as an efficient and long-lasting catalyst for oxidation of H2s on montmorillonite

Removal of highly toxic H2S for pollution control and operational safety is a pressing need. For this purpose, a montmorillonite intercalated with Cu(II)-phenanthroline complex [Cu[(Phen)(H2O)2]2+ (Mt-CuPhen) was prepared to capture gaseous H2S under mild conditions. This hybrid material was simple to obtain and demonstrated an outstanding ability to entrap H2S at room temperature, retaining high efficiency for a very long time (up to 36.8 g of S/100 g Mt-CuPhen after 3 months of exposure). Sorbent and H2S uptake were investigated by elemental analysis, X-ray powder diffraction measurements, diffuse reflectance (DR) UV\u2013Vis and infrared spectroscopy, thermal analysis and evolved gas mass spectrometry, scanning electron microscopy equipped with energy-dispersive X-ray spectrometer, and X-ray absorption spectroscopy. The H2S capture was studied over time and a mechanism of action was proposed. The entrapping involves a catalytic mechanism in which [Cu[(Phen)(H2O)2]2+ acts as catalyst for H2S oxidation to S0 by atmospheric oxygen. The low cost and the long-lasting performance for H2S removal render Mt-CuPhen an extremely appealing trap for H2S removal and a promising material for many technological applications

Prevalence of Lower Urinary Tract Symptoms in China, Taiwan, and South Korea: Results from a Cross-Sectional, Population-Based Study.

INTRODUCTION: Few population-based data are available evaluating the prevalence of lower urinary tract symptoms (LUTS) in Asia. The objective of our study was to determine LUTS prevalence in China, Taiwan, and South Korea using International Continence Society (ICS) 2002 criteria. METHODS: An Internet-based self-administered survey among individuals aged at least 40 years with the ability to use a computer and to read the local language. Survey questions included ICS symptom definitions and the international prostate symptom score (IPSS). Data analysis was based on descriptive statistics and post hoc significance testing. RESULTS: There were 8284 participants, of whom 51% were women and 34% were aged at least 60 years. LUTS prevalence was slightly higher in men than women (62.8% vs. 59.6%; p = 0.004), increasing significantly with age (p = 0.001). All three ICS symptom groups (voiding, storage, and post-micturition) were present in 35% of individuals with LUTS. Symptoms with the highest overall prevalence were nocturia, frequency, incomplete emptying, and terminal dribble. The most bothersome symptoms were terminal dribble, nocturia, and urgency. According to IPSS scores, 87% of participants had at least mild symptoms; 43% of those aged over 60 years had moderate/severe symptoms. The percentage of participants with any LUTS who had visited healthcare professionals because of urinary symptoms was 26%, rising to 45% amongst individuals with all three symptom groups (p = 0.001 vs. other ICS symptom groups). CONCLUSIONS: LUTS are highly prevalent in men and women aged at least 40 years who participated in this study in China, Taiwan, and South Korea and increases with increasing age. A minority of individuals with LUTS seek healthcare and our results suggest an increased patient awareness of LUTS is required. FUNDING: Astellas Pharma Singapore Pte. Ltd. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02618421