Lercanidipine: Short Plasma Half-life, Long Duration of Action and High Cholesterol tolerance. Updated molecular model to rationalize its pharmacokinetic properties

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Urodynamic effects of oxybutynin and tolterodine in conscious and anesthetized rats under different cystometrographic conditions

BACKGROUND: Antimuscarinic agents are the most popular treatment for overactive bladder and their efficacy in man is well documented, producing decreased urinary frequency and an increase in bladder capacity. During cystometry in rats, however, the main effect reported after acute treatment with antimuscarinics is a decrease in peak micturition pressure together with little or no effect on bladder capacity. In the present experiments we studied the effects, in rats, of the two most widely used antimuscarinic drugs, namely oxybutynin and tolterodine, utilising several different cystometrographic conditions. The aim was to determine the experimental conditions required to reproduce the clinical pharmacological effects of antimuscarinic agents, as seen in humans, in particular their ability to increase bladder capacity. RESULTS: Intravenous or oral administration of tolterodine or oxybutynin in conscious rats utilized 1 day after catheter implantation and with saline infusion at constant rate of 0.1 ml/min, gave a dose-dependent decrease of micturition pressure (MP) with no significant change in bladder volume capacity (BVC). When the saline infusion rate into the bladder was decreased to 0.025 ml/min, the effect of oral oxybutynin was similar to that obtained with the higher infusion rate. Also, experiments were performed in rats in which bladders were infused with suramin (3 and 10 μM) in order to block the non-adrenergic, non-cholinergic component of bladder contraction. Under these conditions, oral administration of oxybutynin significantly reduced MP (as observed previously), but again BVC was not significantly changed. In conscious rats with bladders infused with diluted acetic acid, both tolterodine and oxybutynin administered at the same doses as in animals infused with saline, reduced MP, although the reduction appeared less marked, with no effect on BVC. In conscious rats utilized 5 days after catheter implantation, a situation where inflammation due to surgery is reduced, the effect of tolterodine (i.v.) and oxybutynin (p.o.) on MP was smaller and similar, respectively, to that observed in rats utilized 1 day after catheter implantation, but the increase of BVC was not statistically significant. In anesthetized rats, i.v. administration of oxybutynin again induced a significant decrease in MP, although it was of questionable relevance. Both BVC and threshold pressure were not significantly reduced. The number and amplitude of high frequency oscillations in MP were unmodified by treatment. Finally, in conscious obstructed rats, intravenous oxybutynin did not modify frequency and amplitude of non-voiding contractions or bladder capacity and micturition volume. CONCLUSION: Despite the different experimental conditions used, the only effect on cystometrographic parameters of oxybutynin and tolterodine in anesthetized and conscious rats was a decrease in MP, whereas BVC was hardly and non-significantly affected. Therefore, it is difficult to reproduce in rats the cystometrographic increase in BVC as observed in humans after chronic administration of antimuscarinic agents, whereas the acute effects seem more similar

Observing the Evolution of the Universe

How did the universe evolve? The fine angular scale (l>1000) temperature and polarization anisotropies in the CMB are a Rosetta stone for understanding the evolution of the universe. Through detailed measurements one may address everything from the physics of the birth of the universe to the history of star formation and the process by which galaxies formed. One may in addition track the evolution of the dark energy and discover the net neutrino mass. We are at the dawn of a new era in which hundreds of square degrees of sky can be mapped with arcminute resolution and sensitivities measured in microKelvin. Acquiring these data requires the use of special purpose telescopes such as the Atacama Cosmology Telescope (ACT), located in Chile, and the South Pole Telescope (SPT). These new telescopes are outfitted with a new generation of custom mm-wave kilo-pixel arrays. Additional instruments are in the planning stages.Comment: Science White Paper submitted to the US Astro2010 Decadal Survey. Full list of 177 author available at http://cmbpol.uchicago.ed

Caratterizzazione della dinamica produttiva di pascoli naturali italiani

This work studies herbage production and its seasonal distribution in indigenous pastures, and analyses the relationship between the environmental factors (soil, clima, vegetation) and the productivity of these resources. The investigations have been carried on during the period 1983-90 by the joint activity of 10 different University Istitutions in 23 different environments distributed along the Italian peninsula and the main islands. For each environment, pasture production has been measured with the Corrall and Fenlon method, analysing the more important vegetational and ecological conditions; altogether the total yearly production and the seasonal pattern of herbage production have been detected on 104 pastures. The total herbage yield is not significantly influenced by the latitudinal gradient, and the overall regional (alps, central Appenine, south Apennine and islands) production is about 2.3 t ha-1 year-1 The wide range (0.5-6.3 t ha-1 year-1) of herbage production, on small or medium scale, seems to be due to evident changeof environmental or management factors. Five types of seasonal distribution of herbage growth are evidenced with multivariate analysis methods, based on the growing season and the amplitude of the growth. With mean temperature above 12°C and total rainfall below 800 mm, herbage distribution shows a standstill during summer period and an evident regrowth in autumn. On the contrary, for the 4 other distribution types, the winter standstill become important, and the types are distinct by summer growth amplitude and by the growing season lenght. With cluster analysis method, for each type of herbage distribution, have been pointed out under-types characterized by interannual herbage production variation. Among the environmental factors, vegetation characheristics, expressed as Pasture Value following Daget and Poissonet seems to be strictly correlated with total production. The comparative poor role played by the soil and climatic factor, may be due to the strong past and present antropic influence, related with management and utilization techniques. Il presente lavoro ha come scopo l'approfondimento delle conoscenze sulla produzione e sulla distribuzione stagionale della crescita dell'erba dei pascoli naturali, nonché l'analisi delle interazioni tra i fattori ambientali, pedo-climatici e vegetazionali, e la risposta produttiva di queste risorse. La ricerca è stata condotta nel periodo 1983-90 da 10 diverse Istituzioni Universitarie, in 23 ambienti differenti, distribuiti lungo tutta la penisola e le isole maggiori. Per ogni ambiente, con il metodo di rilievo di Corrall e Fenlon, è stata saggiata la risposta produttiva di pascoli rappresentativi delle principali situazioni vegetazionali e di giacitura; complessivamente sono state rilevate la produzione totale annua e la curva di produttività media pluriennale di 104 pascoli. Riguardo la produzione annua complessiva si è osservato che essa non presenta variazioni significative lungo il gradiente latitudinale, collocandosi tra le diverse regioni (alpina, centro appenninica, suq, appenninica e insulare) attorno a 2.3 t ha-1 anno-1. La fitomassa raccolta è soggetta invece a variazioni sensibili (0.5-6.3 t ha-1 anno-1) riconducibili a fattori ambientali e gestionali che si esprimono su piccola e media scala. Con metodi di analisi multivariata si sono individuate 5 tipologie distributive della crescita dell'erba, in rapporto alla stagione vegetativa e alle variazioni dell'intensità di crescita nel corso della stagione stessa. Con temperature medie e precipitazioni annue rispettivamente maggiori di 12°C e minori di 800 mm, risulta evidente la stasi vegetativa nel trimestre estivo e la ripresa vegetativa autunnale. Nel caso opposto la stasi è invernale e le 4 tipologie afferenti a questo modello, sono distinguibili dall'entità della crescita nei mesi estivi e dalla durata della stagione vegetativa. Per ogni tipologia produttiva, sono state evidenziate, tramite l'analisi cluster, sotto-tipologie distinte per la variabilità produttiva interannuale. Tra i fattori ambientali, la vegetazione, espressa attraverso l'indice del valore pastorale di Daget e Poissonet, presenta una buona capacità predittiva nei confronti del livello produttivo dei pascoli. Il contributo comparativamente modesto offerto dai fattori pedoclimatici sembra attribuibile alla forte influenza antropica, pregressa e attuale, attraverso le cure colturali e l'utilizzazione

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Measurement of the top quark mass using charged particles in pp collisions at root s=8 TeV

Peer reviewe

Measurement of t(t)over-bar normalised multi-differential cross sections in pp collisions at root s=13 TeV, and simultaneous determination of the strong coupling strength, top quark pole mass, and parton distribution functions

Peer reviewe

Search for supersymmetry in events with one lepton and multiple jets in proton-proton collisions at root s=13 TeV

Peer reviewe

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| < 0.03 at 95% confidence level. [Figure not available: see fulltext.

An embedding technique to determine ττ backgrounds in proton-proton collision data

An embedding technique is presented to estimate standard model tau tau backgrounds from data with minimal simulation input. In the data, the muons are removed from reconstructed mu mu events and replaced with simulated tau leptons with the same kinematic properties. In this way, a set of hybrid events is obtained that does not rely on simulation except for the decay of the tau leptons. The challenges in describing the underlying event or the production of associated jets in the simulation are avoided. The technique described in this paper was developed for CMS. Its validation and the inherent uncertainties are also discussed. The demonstration of the performance of the technique is based on a sample of proton-proton collisions collected by CMS in 2017 at root s = 13 TeV corresponding to an integrated luminosity of 41.5 fb(-1).Peer reviewe