New standards in hypertension and cardiovascular risk management: focus on telmisartan

Blockade of the renin–angiotensin system is an important approach in managing high blood pressure, and has increasingly been shown to affect cardiovascular disease processes mediated by angiotensin II throughout the cardiovascular and renal continua. Telmisartan is an angiotensin II receptor blocker (ARB) displaying unique pharmacologic properties, including a longer half life than any other ARB, that result in large and sustained reductions of blood pressure. In patients with mild-to-moderate hypertension, telmisartan has proved superior to other antihypertensive agents (valsartan, losartan, ramipril, perindopril, and atenolol) in controlling blood pressure particularly towards the end of the dosing interval. There is also clinical evidence that telmisartan reduces left ventricular hypertrophy, reduces arterial stiffness and the recurrence of atrial fibrillation, and confers renoprotection. The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET®) study has demonstrated that telmisartan has similar cardiovascular protective effects to ramipril in a large, high-risk patient population but was better tolerated. The powerful and sustained blood pressure control apparent in clinical trials, together with cardiovascular protection and tolerability demonstrated in ONTARGET® means that telmisartan may be a preferred option for patients with hypertension

Systemic Mastocytosis - a Diagnostic Challenge

Mastocytosis refers to a group of disorders characterized by the infiltration of clonally derived mast cells to the skin or extracutaneous tissues resulting in a heterogeneous clinical picture. It is a rare hematologic disorder in all its forms. The exact incidence is unknown; it affects patients of any age and males and females equally. Its molecular pathogenesis is incompletely understood. The clinical features of mastocytosis result from both chronic and episodic mast cell mediator release, signs and symptoms arising from diffuse or focal tissue infiltration, and, occasionally, the presence of an associated non-mast cell clonal hematologic disease. The histopathologic analysis is essential for definitive diagnosis but there is no curative treatment. The authors report a clinical case of a 72-year-old woman with no history of allergies, with bicytopenia, weight loss, and diffuse axial osteolytic lesions. This is a rare clinical case of aggressive systemic mastocytosis for which palliative treatment can improve survival and quality of life. A brief review of the literature about this pathology is also included

Supervised Relevance-Redundancy assessments for feature selection in omics-based classification scenarios

Background and objective: Many classification tasks in translational bioinformatics and genomics are characterized by the high dimensionality of potential features and unbalanced sample distribution among classes. This can affect classifier robustness and increase the risk of overfitting, curse of dimensionality and generalization leaks; furthermore and most importantly, this can prevent obtaining adequate patient stratification required for precision medicine in facing complex diseases, like cancer. Setting up a feature selection strategy able to extract only proper predictive features by removing irrelevant, redundant, and noisy ones is crucial to achieving valuable results on the desired task. Methods: We propose a new feature selection approach, called ReRa, based on supervised Relevance-Redundancy assessments. ReRa consists of a customized step of relevance-based filtering, to identify a reduced subset of meaningful features, followed by a supervised similarity-based procedure to minimize redundancy. This latter step innovatively uses a combination of global and class-specific similarity assessments to remove redundant features while preserving those differentiated across classes, even when these classes are strongly unbalanced. Results: We compared ReRa with several existing feature selection methods to obtain feature spaces on which performing breast cancer patient subtyping using several classifiers: we considered two use cases based on gene or transcript isoform expression. In the vast majority of the assessed scenarios, when using ReRa-selected feature spaces, the performances were significantly increased compared to simple feature filtering, LASSO regularization, or even MRmr - another Relevance-Redundancy method. The two use cases represent an insightful example of translational application, taking advantage of ReRa capabilities to investigate and enhance a clinically-relevant patient stratification task, which could be easily applied also to other cancer types and diseases. Conclusions: ReRa approach has the potential to improve the performance of machine learning models used in an unbalanced classification scenario. Compared to another Relevance-Redundancy approach like MRmr, ReRa does not require tuning the number of preserved features, ensures efficiency and scalability over huge initial dimensionalities and allows re-evaluation of all previously selected features at each iteration of the redundancy assessment, to ultimately preserve only the most relevant and class-differentiated features

Primary gas thermometry by means of laser-absorption spectroscopy: Determination of the Boltzmann constant

We report on a new optical implementation of primary gas thermometry based on laser absorption spectrometry in the near infrared. The method consists in retrieving the Doppler broadening from highly accurate observations of the line shape of the R(12) $\nu_{1} + 2 \nu_{2}^{\phantom{1}0} + \nu_{3}$ transition in CO$_{2}$ gas at thermodynamic equilibrium. Doppler width measurements as a function of gas temperature, ranging between the triple point of water and the gallium melting point, allowed for a spectroscopic determination of the Boltzmann constant with a relative accuracy of $\sim1.6\times10^{-4}$.Comment: Submitted to Physical Review Letter

Frequency-noise measurements of optical frequency combs by multiple fringe-side discriminator

open5noThe frequency noise of an optical frequency comb is routinely measured through the hetherodyne beat of one comb tooth against a stable continuous-wave laser. After frequency-to-voltage conversion, the beatnote is sent to a spectrum analyzer to retrive the power spectral density of the frequency noise. Because narrow-linewidth continuous-wave lasers are available only at certain wavelengths, heterodyning the comb tooth can be challenging. We present a new technique for direct characterization of the frequency noise of an optical frequency comb, requiring no supplementary reference lasers and easily applicable in all spectral regions from the terahertz to the ultraviolet. The technique is based on the combination of a low finesse Fabry-Perot resonator and the so-called "fringe-side locking" method, usually adopted to characterize the spectral purity of single-frequency lasers, here generalized to optical frequency combs. The effectiveness of this technique is demonstrated with an Er-fiber comb source across the wavelength range from 1 to 2 μm.Coluccelli, Nicola; Cassinerio, Marco; Gambetta, Alessio; Laporta, Paolo; Galzerano, GianlucaColuccelli, Nicola; Cassinerio, Marco; Gambetta, Alessio; Laporta, Paolo; Galzerano, Gianluc

Intracavity intensity noise suppression in the inverse Compton scattering source BriXSinO exploiting carrier-envelope offset manipulation

We report on a technique that exploits the control of the carrier -envelope offset to suppress the frequency-to-intensity noise conversion in the locking of a mode-locking laser against a high-finesse optical enhancement resonator. A proper combination of the laser carrier-envelope offset and the resonator finesse allows the improvement of the signal-to-noise ratio of the optical intensity trapped into the optical resonator. In this paper, we show the application of this technique in the laser system of the inverse Compton scattering source BriXSinO, currently under development in Milan, Italy, demonstrating the possibility of achieving an intracavity intensity noise reduction of a factor of 20

La fine del mondo nel ›De rerum natura‹ di Lucrezio

Lucretius’ De rerum natura can be considered as the first Latin “apocalyptic” poem and, at the same time, the most important source on Epicurean cosmic eschatology. This book examines Lucretius’ treatment of the mortality of the world, in order to identify the poet’s sources and polemical targets and to illustrate his eschatological imagery and rhetoric strategies

Low frequency-to-intensity noise conversion in a pulsed laser cavity locking by exploiting carrier envelope offset

We report on the dependence of the frequency-to-intensity noise conversion in the locking of an ultrafast laser against a high-finesse optical enhancement resonator from the carrier envelope offset frequency. By a proper combination of the cavity finesse and laser carrier envelope offset frequency, it is possible to optimize the signal-to-noise ratio of the laser intensity trapped into the optical resonator. In this paper, we describe the effect of the laser-enhancement cavity coupling on the intracavity power relative noise, and we demonstrate both theoretically and experimentally its reduction