Cannabinoids in the treatment of epilepsy: current status and future prospects

Cannabidiol (CBD) is one of the prominent phytocannabinoids found in Cannabis sativa, differentiating from Δ9-tetrahydrocannabinol (THC) for its non-intoxicating profile and its antianxiety/antipsychotic effects. CBD is a multi-target drug whose anti-convulsant properties are supposed to be independent of endocannabinoid receptor CB1 and might be related to several underlying mechanisms, such as antagonism on the orphan GPR55 receptor, regulation of adenosine tone, activation of 5HT1A receptors and modulation of calcium intracellular levels. CBD is a lipophilic compound with low oral bioavailability (6%) due to poor intestinal absorption and high first-pass metabolism. Its exposure parameters are greatly influenced by feeding status (ie, high fatcontaining meals). It is mainly metabolized by cytochrome P 450 (CYP) 3A4 and 2C19, which it strongly inhibits. A proprietary formulation of highly purified, plant-derived CBD has been recently licensed as an adjunctive treatment for Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS), while it is being currently investigated in tuberous sclerosis complex. The regulatory agencies’ approval was granted based on four pivotal double-blind, placebocontrolled, randomized clinical trials (RCTs) on overall 154 DS patients and 396 LGS ones, receiving CBD 10 or 20 mg/kg/day BID as active treatment. The primary endpoint (reduction in monthly seizure frequency) was met by both CBD doses. Most patients reported adverse events (AEs), generally from mild to moderate and transient, which mainly consisted of somnolence, sedation, decreased appetite, diarrhea and elevation in aminotransferase levels, the last being documented only in subjects on concomitant valproate therapy. The interaction between CBD and clobazam, likely due to CYP2C19 inhibition, might contribute to some AEs, especially somnolence, but also to CBD clinical effectiveness. Cannabidivarin (CBDV), the propyl analogue of CBD, showed anti-convulsant properties in pre-clinical studies, but a plant-derived, purified proprietary formulation of CBDV recently failed the Phase II RCT in patients with uncontrolled focal seizures

Information-flux approach to multiple-spin dynamics

We introduce and formalize the concept of information flux in a many-body register as the influence that the dynamics of a specific element receive from any other element of the register. By quantifying the information flux in a protocol, we can design the most appropriate initial state of the system and, noticeably, the distribution of coupling strengths among the parts of the register itself. The intuitive nature of this tool and its flexibility, which allow for easily manageable numerical approaches when analytic expressions are not straightforward, are greatly useful in interacting many-body systems such as quantum spin chains. We illustrate the use of this concept in quantum cloning and quantum state transfer and we also sketch its extension to non-unitary dynamics.Comment: 7 pages, 4 figures, RevTeX

Joint searches between gravitational-wave interferometers and high-energy neutrino telescopes: science reach and analysis strategies

Many of the astrophysical sources and violent phenomena observed in our Universe are potential emitters of gravitational waves (GWs) and high-energy neutrinos (HENs). A network of GW detectors such as LIGO and Virgo can determine the direction/time of GW bursts while the IceCube and ANTARES neutrino telescopes can also provide accurate directional information for HEN events. Requiring the consistency between both, totally independent, detection channels shall enable new searches for cosmic events arriving from potential common sources, of which many extra-galactic objects.Comment: 4 pages. To appear in the Proceedings of the 2d Heidelberg Workshop: "High-Energy Gamma-rays and Neutrinos from Extra-Galactic Sources", Heidelberg (Germany), January 13-16, 200

Parental evaluation of a telemonitoring service for children with Type 1 Diabetes

Introduction In the past years, we developed a telemonitoring service for young patients affected by Type 1 Diabetes. That service provides data to the clinical staff and offers an important tool to the parents, that are able to oversee in real time their children. The aim of this work was to analyze the parents' perceived usefulness of the service. Methods The service was tested by the parents of 31 children enrolled in a seven-day clinical trial during a summer camp. To study the parents' perception we proposed and analyzed two questionnaires. A baseline questionnaire focused on the daily management and implications of their children's diabetes, while a post-study one measured the perceived benefits of telemonitoring. Questionnaires also included free text comment spaces. Results Analysis of the baseline questionnaires underlined the parents' suffering and fatigue: 51% of total responses showed a negative tendency and the mean value of the perceived quality of life was 64.13 in a 0-100 scale. In the post-study questionnaires about half of the parents believed in a possible improvement adopting telemonitoring. Moreover, the foreseen improvement in quality of life was significant, increasing from 64.13 to 78.39 ( p-value\u2009=\u20090.0001). The analysis of free text comments highlighted an improvement in mood, and parents' commitment was also proved by their willingness to pay for the service (median\u2009=\u2009200\u2009euro/year). Discussion A high number of parents appreciated the telemonitoring service and were confident that it could improve communication with physicians as well as the family's own peace of mind

Therapeutic approach in glioblastoma multiforme with primitive neuroectodermal tumor components: case report and review of the literature

Glioblastoma multiforme (GBM) is the most common and aggressive malignant glioma that is treated with first-line therapy, using surgical resection followed by local radiotherapy and concomitant/adjuvant temozolomide (TMZ) treatment. GBM is characterised by a high local recurrence rate and a low response to therapy. Primitive neuroectodermal tumour (PNET) of the brain revealed a low local recurrence rate; however, it also exhibited a high risk of cerebrospinal fluid (CSF) dissemination. PNET is treated with surgery followed by craniospinal irradiation (CSI) and platinum-based chemotherapy in order to prevent CSF dissemination. GBM with PNET-like components (GBM/PNET) is an emerging variant of GBM, characterised by a PNET-like clinical behaviour with an increased risk of CSF dissemination; it also may benefit from platinum-based chemotherapy upfront or following failure of GBM therapy. The results presented regarding the management of GBM/PNET are based on case reports or case series, so a standard therapeutic approach for GBM/PNET is not defined, constituing a challenging diagnostic and therapeutic dilemma. In this report, a case of a recurrent GBM/PNET treated with surgical resection and radiochemotherapy as Stupp protocol, and successive platinum-based chemotherapy due to the development of leptomeningeal dissemintation and an extracranial metastasis, is discussed. A review of the main papers regarding this rare GBM variant and its therapeutic approach are also reported. In conclusion, GBM/PNET should be treated with a multimodal approach including surgery, chemoradiotherapy, and/or the early introduction of CSI and platinum-based chemotherapy upfront or at recurrence

Ionome variations in tomato Introgressed Lines (Solanum Pennellii x S. Lycopersicum cv. M82) following metal treatements shed new light on food health.

A tomato introgression line population that combines single chromosomal segments introgressed from the wild, green fruited species Solanum pennelli in the background of the domesticated tomato, S. lycopersicum cv. M82, was used in this study. Results shed light both on the metal accumulation of ILs tomato plants and on theirs ionome modifications

In the eye of the storm : the Italian economy and the eurozone crisis

The eurozone crisis had a more significant and longer-lasting impact on Italy than on virtually any other member state, with the effects still visible a decade after. The extent of the shock was surprising in view of progress Italy had apparently made in the 1990s in terms of enhancing its capacity to meet the demands of European Monetary Union. The explanation for this traumatic economic experience lies in Italy’s deep, long-term, structural tensions which were placed under severe pressure during the 1990s and which were cracked open by the 2011 sovereign debt crisis. These have had long-standing economic effects as well as political ramifications in terms of a significant change in the Italy–EU relationship

Ongoing spread of colistin-resistant Klebsiella pneumoniae in different wards of an acute general hospital, Italy, June to December 2011

We describe polyclonal spread of colistin-resistant Klebsiella pneumoniae in an acute general hospital in Italy. Between June and December 2011, 58 colistin-resistant K. pneumoniae isolates were recovered from 28 patients admitted to different wards, but mainly in the intensive care units. All isolates were tested for drug susceptibility and the presence of beta-lactamase (bla) genes. Clonality was investigated by repetitive extragenic palindromic (rep)-PCR and multilocus sequence typing (MLST). Fifty-two isolates had minimum inhibitory concentrations (MICs) for colistin of 6-128 mg/L, carried bla(KPC3) and were attributed to sequence type ST258. The remaining six isolates were susceptible to carbapenems, exhibited MICs for colistin of 3-32 mg/L, and belonged to two different types, ST15 and ST273. Rep-PCR included all isolates in three clusters, one containing all ST258 KPC-3-producing isolates and two containing ST15 and ST273 isolates.Cross-transmission containment measures and intensification of staff and environmental hygiene could not stop the outbreak. Selective pressure and horizontal transmission probably contributed to emergence and spread of three different strains of colistin-resistant K. pneumoniae in the hospital. Strict implementation of the above measures and a wider awareness of the antimicrobial resistance threat are crucial to preserve the last therapeutic options of the multidrug-resistant Gram-negative infection

Towards the QFT on Curved Spacetime Limit of QGR. I: A General Scheme

In this article and a companion paper we address the question of how one might obtain the semiclassical limit of ordinary matter quantum fields (QFT) propagating on curved spacetimes (CST) from full fledged Quantum General Relativity (QGR), starting from first principles. We stress that we do not claim to have a satisfactory answer to this question, rather our intention is to ignite a discussion by displaying the problems that have to be solved when carrying out such a program. In the present paper we propose a scheme that one might follow in order to arrive at such a limit. We discuss the technical and conceptual problems that arise in doing so and how they can be solved in principle. As to be expected, completely new issues arise due to the fact that QGR is a background independent theory. For instance, fundamentally the notion of a photon involves not only the Maxwell quantum field but also the metric operator - in a sense, there is no photon vacuum state but a "photon vacuum operator"! While in this first paper we focus on conceptual and abstract aspects, for instance the definition of (fundamental) n-particle states (e.g. photons), in the second paper we perform detailed calculations including, among other things, coherent state expectation values and propagation on random lattices. These calculations serve as an illustration of how far one can get with present mathematical techniques. Although they result in detailed predictions for the size of first quantum corrections such as the gamma-ray burst effect, these predictions should not be taken too seriously because a) the calculations are carried out at the kinematical level only and b) while we can classify the amount of freedom in our constructions, the analysis of the physical significance of possible choices has just begun.Comment: LaTeX, 47 p., 3 figure

INFN Camera demonstrator for the Cherenkov Telescope Array

The Cherenkov Telescope Array is a world-wide project for a new generation of ground-based Cherenkov telescopes of the Imaging class with the aim of exploring the highest energy region of the electromagnetic spectrum. With two planned arrays, one for each hemisphere, it will guarantee a good sky coverage in the energy range from a few tens of GeV to hundreds of TeV, with improved angular resolution and a sensitivity in the TeV energy region better by one order of magnitude than the currently operating arrays. In order to cover this wide energy range, three different telescope types are envisaged, with different mirror sizes and focal plane features. In particular, for the highest energies a possible design is a dual-mirror Schwarzschild-Couder optical scheme, with a compact focal plane. A silicon photomultiplier (SiPM) based camera is being proposed as a solution to match the dimensions of the pixel (angular size of ~ 0.17 degrees). INFN is developing a camera demonstrator made by 9 Photo Sensor Modules (PSMs, 64 pixels each, with total coverage 1/4 of the focal plane) equipped with FBK (Fondazione Bruno Kessler, Italy) Near UltraViolet High Fill factor SiPMs and Front-End Electronics (FEE) based on a Target 7 ASIC, a 16 channels fast sampler (up to 2GS/s) with deep buffer, self-trigger and on-demand digitization capabilities specifically developed for this purpose. The pixel dimensions of $6\times6$ mm$^2$ lead to a very compact design with challenging problems of thermal dissipation. A modular structure, made by copper frames hosting one PSM and the corresponding FEE, has been conceived, with a water cooling system to keep the required working temperature. The actual design, the adopted technical solutions and the achieved results for this demonstrator are presented and discussed.Comment: In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions at arXiv:1508.0589