The 3-D structure of the Somma-Vesuvius volcanic complex (Italy) inferred from new and historic gravimetric data

Existing 3-D density models of the Somma-Vesuvius volcanic complex (SVVC), Italy, largely disagree. Despite the scientific and socioeconomic importance of Vesuvius, there is no reliable 3-D density model of the SVVC. A considerable uncertainty prevails concerning the presence (or absence) of a dense body underlying the Vesuvius crater (1944 eruption) that is implied from extensive seismic investigations. We have acquired relative gravity measurements at 297 stations, including measurements in difficult-to-access areas (e.g., the first-ever measurements in the crater). In agreement with seismic investigations, the simultaneous inversion of these and historic data resolves a high-density body that extends from the surface of the Vesuvius crater down to depths that exceed 2 km. A 1.5-km radius horseshoe-shaped dense feature (open in the southwestern sector) enforces the existing model of groundwater circulation within the SVVC. Based on its volcano-tectonic evolution, we interpret volcanic structures that have never been imaged before

Relationship between Bispectral Index, electroencephalographic state entropy and effect-site EC 50 for propofol at different clinical endpoints

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Relationship between Bispectral Index, electroencephalographic state entropy and effect-site EC 50 for propofol at different clinical endpoints

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Noncommutative Electrodynamics

In this paper we define a causal Lorentz covariant noncommutative (NC) classical Electrodynamics. We obtain an explicit realization of the NC theory by solving perturbatively the Seiberg-Witten map. The action is polynomial in the field strenght $F$, allowing to preserve both causality and Lorentz covariance. The general structure of the Lagrangian is studied, to all orders in the perturbative expansion in the NC parameter $\theta$. We show that monochromatic plane waves are solutions of the equations of motion to all orders. An iterative method has been developed to solve the equations of motion and has been applied to the study of the corrections to the superposition law and to the Coulomb law.Comment: 13 pages, 2 figures, one reference adde

The New Paradigms in Clinical Research: From Early Access Programs to the Novel Therapeutic Approaches for Unmet Medical Needs.

Despite several innovative medicines gaining worldwide approval in recent years, there are still therapeutic areas for which unsatisfied therapeutic needs persist. For example, high unmet clinical need was observed in patients diagnosed with type 2 diabetes mellitus and hemophilia, as well as in specific age groups, such as the pediatric population. Given the urgent need to improve the therapy of clinical conditions for which unmet clinical need is established, clinical testing, and approval of new medicines are increasingly being carried out through accelerated authorization procedures. Starting from 1992, the Food and Drug Administration and the European Medicines Agency have supported the so-called Early Access Programs (EAPs). Such procedures, which can be based on incomplete clinical data, allow an accelerated marketing authorization for innovative medicines. The growth in pharmaceutical research has also resulted in the development of novel therapeutic approaches, such as biotech drugs and advanced therapy medicinal products, including new monoclonal antibodies for the treatment of asthma, antisense oligonucleotides for the treatment of Duchenne muscular dystrophy and spinal muscular atrophy, and new anticancer drugs that act on genetic biomarkers rather than any specific type of cancer. Even though EAPs and novel therapeutic approaches have brought huge benefits for public health, their implementation is limited by several challenges, including the high risk of safety-related label changes for medicines authorized through the accelerated procedure, the high costs, and the reimbursement and access concerns. In this context, regulatory agencies should provide the best conditions for the implementation of the described new tools

Chemotherapeutic Drugs and Mitochondrial Dysfunction: Focus on Doxorubicin, Trastuzumab, and Sunitinib.

Many cancer therapies produce toxic side effects whose molecular mechanisms await full elucidation. The most feared and studied side effect of chemotherapeutic drugs is cardiotoxicity. Also, skeletal muscle physiology impairment has been recorded after many chemotherapeutical treatments. However, only doxorubicin has been extensively studied for its side effects on skeletal muscle. Chemotherapeutic-induced adverse side effects are, in many cases, mediated by mitochondrial damage. In particular, trastuzumab and sunitinib toxicity is mainly associated with mitochondria impairment and is mostly reversible. Vice versa, doxorubicin-induced toxicity not only includes mitochondria damage but can also lead to a more robust and extensive cell injury which is often irreversible and lethal. Drugs interfering with mitochondrial functionality determine the depletion of ATP reservoirs and lead to subsequent reversible contractile dysfunction. Mitochondrial damage includes the impairment of the respiratory chain and the loss of mitochondrial membrane potential with subsequent disruption of cellular energetic. In a context of increased stress, AMPK has a key role in maintaining energy homeostasis, and inhibition of the AMPK pathway is one of the proposed mechanisms possibly mediating mitochondrial toxicity due to chemotherapeutics. Therapies targeting and protecting cell metabolism and energy management might be useful tools in protecting muscular tissues against the toxicity induced by chemotherapeutic drugs

Cytokines and VEGF Induction in Orthodontic Movement in Animal Models

Orthodontics is a branch of dentistry that aims at the resolution of dental malocclusions. The specialist carries out the treatment using intraoral or extraoral orthodontic appliances that require forces of a given load level to obtain a tooth movement in a certain direction in dental arches. Orthodontic tooth movement is dependent on efficient remodeling of periodontal ligament and alveolar bone, correlated with several biological and mechanical responses of the tissues surrounding the teeth. A periodontal ligament placed under pressure will result in bone resorption whereas a periodontal ligament under tension results in bone formation. In the primary stage of the application of orthodontic forces, an acute inflammation occurs in periodontium. Several proinflammatory cytokines are produced by immune-competent cells migrating by means of dilated capillaries. In this paper we summarize, also through the utilization of animal models, the role of some of these molecules, namely, interleukin-1β and vascular endothelial growth factor, that are some proliferation markers of osteoclasts and osteoblasts, and the macrophage colony stimulating factor