1,721,521 research outputs found
Coxibs: a significant therapeutic opportunity.
No full textPain is the main reason why people decide to see a doctor; hence, the widespread use of anti-inflammatory drugs which were specifically developed to control pain and inflammation. One of the main causes of pain is represented by osteoarticular conditions, the most common one being arthrosis. Paracetamol is universally indicated as the therapy of first choice in degenerative pathologies of the joints, although it is often insufficient to control adequately the clinical picture and less efficacious than anti-inflammatory drugs. These latter, however, especially when taken chronically, exhibit an unfavourable safety profile. The most common side effect of anti-inflammatory drugs is gastric discomfort; coxibs - COX-2 selective inhibitors - were developed to solve this problem. The use of these drugs, relative to conventional NSAIDs, is associated to a significantly lesser gastroduodenal ulcer rate and to fewer clinically relevant complications, as well as to a smaller rate of treatment discontinuation due to gastrointestinal (GI) symptoms. From a clinical and practical standpoint, the use of coxibs is associated to a remarkably reduced risk of gastroduodenal lesions, similar as the one resulting from the combination of a conventional NSAID and a proton-pump inhibitor. By adding a proton-pump inhibitor to a coxib, such risk seems to become virtually non-existent, even in a high risk population and regardless of ASA administration. It is important to stress that the better tolerability of coxibs does not imply an inferior anti-inflammatory and pain-relieving efficacy, especially with regard to etoricoxib, whose efficacy is at least equivalent as other competing NSAIDs, even in quite severe and complex musculoskeletal pain models. This clear-cut advantage of coxibs at gastric level clashed against a documented increased cardiovascular (CV) risk, which led to the much-talked-about withdrawal of rofecoxib from the market. The most credited pathogenetic hypothesis to explain the association between chronic use of coxibs and CV risk seems to be related to a trombophilic effect due to an imbalance of prothrombotic and antithrombotic factors. Several observational and case-control studies, however, led to suspect that conventional NSAIDs share with coxibs an increased cardiovascular risk; such suspicion was experimentally confirmed by the MEDAL trial. In this trial, the cardiovascular risk of thrombosis among patients who were treated on a long-term basis with a coxib (etoricoxib) was shown to be similar as the risk observed in patients receiving a conventional NSAID (diclofenac). In conclusion, coxibs represent a valid therapeutic option in the treatment of patients with osteoarticular conditions. In terms of cardiovascular risk their efficacy is associated to a similar safety profile as conventional NSAIDs, whereas the gastrointestinal risk related to coxibs seems to be significantly lesser
Reynolds-number dependence of turbulent skin-friction drag reduction induced by spanwise forcing
Get PDFThis paper examines how increasing the value of the Reynolds number affects the ability of spanwise-forcing techniques to yield turbulent skin-friction drag reduction. The considered forcing is based on the streamwise-travelling waves of spanwise-wall velocity (Quadrio et al., J. Fluid Mech., vol. 627, 2009, pp. 161-178). The study builds upon an extensive drag-reduction database created via direct numerical simulation of a turbulent channel flow for two fivefold separated values of Re, namely Reτ=200 and Reτ=1000 The sheer size of the database, which for the first time systematically addresses the amplitude of the forcing, allows a comprehensive view of the drag-reducing characteristics of the travelling waves, and enables a detailed description of the changes occurring when increases. The effect of using a viscous scaling based on the friction velocity of either the non-controlled flow or the drag-reduced flow is described. In analogy with other wall-based drag-reduction techniques, like riblets for example, the performance of the travelling waves is well described by a vertical shift of the logarithmic portion of the mean streamwise velocity profile. Except when is very low, this shift remains constant with, at odds with the percentage reduction of the friction coefficient, which is known to present a mild, logarithmic decline. Our new data agree with the available literature, which is however mostly based on low-information and hence predicts a quick drop of maximum drag reduction with . The present study supports a more optimistic scenario, where for an airplane at flight Reynolds numbers a drag reduction of nearly 30 % would still be possible thanks to the travelling waves
Pharmacological management of osteoporosis in postmenopausal women: The current state of the art
No full textOsteoporosis is a common disease that increases fracture risk. Fragility fractures bring heavy consequences in terms of mortality and disability, with burdensome health and social costs. In subjects with clinical bone fragility, the first goal is to identify the secondary forms of osteoporosis, especially in young subjects, in males and in patients who recently experienced a fragility fracture. In addition, before considering any sort of treatment, it is fundamental to check for adequate calcium and vitamin D intake, since their deficiency is the most common reason for drug failure.In the last decade of the 20th century, several molecules have been developed and proved to be effective in achieving the true goal of any antiosteoporotic drug: fracture prevention.In this article, we considered the most commonly prescribed antiresorptive drugs (hormonal therapy, bisphosphonates, and denosumab), the anabolic agents (teriparatide), the dual-action drugs (romosozumab), and the drugs characterized by an unclear mechanism of action (strontium ranelate) to provide physicians with useful insights for their clinical practice. We discussed the main criteria for the appropriate choice selection and management of each treatment. Finally, we addressed the current controversies related to treatment discontinuation, sequential, and combination therapy
Friedmann–Robertson–Walker transformational technique in paraxial wave optics
No full textWe introduce in optics a transformational technique inspired by the Friedmann–Robertson–Walker (FRW) cosmology.
We found that the extended covariant scaling transformation used in the FRW theory can be applied to
light wave phenomena under scalar paraxial approximation. Our method provides new ways to propagate light
beams as well as novel guidelines for advanced optical structure design, as discussed in some application examples.
In the first example we study Talbot imaging in different configurations comprising illumination with spherical
beams or with Gaussian beams and propagation in homogeneous or inhomogeneous gradient-index media. In the
second example we derive an exact analytical solution for the propagation of self-accelerating parabolic beams in
parabolic gradient-index media. Finally, in the third example we show how the new insightful transformational
method can be exploited to design lossless nonadiabatic waveguide tapers and adapters
Non-Hermitian transparency and one-way transport in low-dimensional lattices by an imaginary gauge field
Full text linkUnidirectional and robust transport is generally observed at the edge of two- or three-dimensional quantum
Hall and topological insulator systems. A hallmark of these systems is topological protection, i.e., the existence
of propagative edge states that cannot be scattered by imperfections or disorder in the system. A different and
less explored form of robust transport arises in non-Hermitian systems in the presence of an imaginary gauge
field. As compared to topologically protected transport in quantum Hall and topological insulator systems, robust
non-Hermitian transport can be observed in lower dimensional (i.e., one dimensional) systems. In this work
the transport properties of one-dimensional tight-binding lattices with an imaginary gauge field are theoretically
investigated, and the physical mechanism underlying robust one-way transport is highlighted. Back scattering
is here forbidden because reflected waves are evanescent rather than propagative. Remarkably, the spectral
transmission of the non-Hermitian lattice is shown to be mapped onto the one of the corresponding Hermitian
lattice, i.e., without the gauge field, but computed in the complex plane. In particular, at large values of the gauge
field the spectral transmittance becomes equal to 1, even in the presence of disorder or lattice imperfections. This
phenomenon can be referred to as one-way non-Hermitian transparency. Robust one-way transport can be also
realized in a more realistic setting, namely in heterostructure systems, in which a non-Hermitian disordered lattice
is embedded between two homogeneous Hermitian lattices. Such a double heterostructure realizes asymmetric
(nonreciprocal) wave transmission. A physical implementation of non-Hermitian transparency, based on light
transport in a chain of optical microring resonators, is suggested
Robust light transport in non-Hermitian photonic lattices
Full text linkCombating the effects of disorder on light transport in micro- and nano-integrated photonic devices
is of major importance from both fundamental and applied viewpoints. In ordinary waveguides,
imperfections and disorder cause unwanted back-reflections, which hinder large-scale optical
integration. Topological photonic structures, a new class of optical systems inspired by quantum
Hall effect and topological insulators, can realize robust transport via topologically-protected
unidirectional edge modes. Such waveguides are realized by the introduction of synthetic gauge
fields for photons in a two-dimensional structure, which break time reversal symmetry and enable
one-way guiding at the edge of the medium. Here we suggest a different route toward robust
transport of light in lower-dimensional (1D) photonic lattices, in which time reversal symmetry is
broken because of the non-Hermitian nature of transport. While a forward propagating mode in
the lattice is amplified, the corresponding backward propagating mode is damped, thus resulting
in an asymmetric transport insensitive to disorder or imperfections in the structure. Non-Hermitian
asymmetric transport can occur in tight-binding lattices with an imaginary gauge field via a non-
Hermitian delocalization transition, and in periodically-driven superlattices. The possibility to observe
non-Hermitian delocalization is suggested using an engineered coupled-resonator optical waveguide
(CROW) structure
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