The M4 Core Project with HST - IV. Internal Kinematics from Accurate Radial Velocities of 2771 Cluster Members

We present a detailed study of the internal kinematics of the Galactic Globular Cluster M 4 (NGC 6121), by deriving the radial velocities from 7250 spectra for 2771 stars distributed from the upper part of the Red Giant Branch down to the Main Sequence. We describe new approaches to determine the wavelength solution from day-time calibrations and to determine the radial velocity drifts that can occur between calibration and science observations when observing with the GIRAFFE spectrograph at VLT. Two techniques to determine the radial velocity are compared, after a qualitative description of their advantages with respect to other commonly used algorithm, and a new approach to remove the sky contribution from the spectra obtained with fibre-fed spectrograph and further improve the radial velocity precision is presented. The average radial velocity of the cluster is $\langle v \rangle = 71.08 \pm 0.08$ km s$^{-1}$ with an average dispersion of $\mu_{v_c} = 3.97$ km s$^{-1}$. Using the same dataset and the same statistical approach of previous analyses, 20 additional binary candidates are found, for a total of 87 candidates. A new determination of the internal radial velocity dispersion as a function of cluster distance is presented, resulting in a dispersion of $4.5$ km s$^{-1}$ within 2$^{\prime}$ from the center of cluster and steadily decreasing outward. We statistically confirm the small amplitude of the cluster rotation, as suggested in the past by several authors. This new analysis represents a significant improvement with respect to previous results in literature and provides a fundamental observational input for the modeling of the cluster dynamics.Comment: 17 pages, 17 figures. Accepted for publication in MNRAS on September 15, 201

Sustainability ranking of desalination plants using Mamdani Fuzzy Logic Inference Systems

As water desalination continues to expand globally, desalination plants are continually under pressure to meet the requirements of sustainable development. However, the majority of desalination sustainability research has focused on new desalination projects, with limited research on sustainability performance of existing desalination plants. This is particularly important while considering countries with limited resources for freshwater such as the United Arab Emirates (UAE) as it is heavily reliant on existing desalination infrastructure. In this regard, the current research deals with the sustainability analysis of desalination processes using a generic sustainability ranking framework based on Mamdani Fuzzy Logic Inference Systems. The fuzzy-based models were validated using data from two typical desalination plants in the UAE. The promising results obtained from the fuzzy ranking framework suggest this more in-depth sustainability analysis should be beneficial due to its flexibility and adaptability in meeting the requirements of desalination sustainability

S-ICD is effective in preventing sudden death in Arrhythmogenic Cardiomyopathy athletes during exercise

Here we describe the cases of two elite athletes, with a diagnosis of Arrhythmogenic Cardiomyopathy (ACM), in which a Subcutaneous Implantable Cardioverter Defibrillator (S-ICD) has been implanted. Both patients experienced a ventricular tachycardia during exercise and received effective S-ICD shocks that interrupted arrhythmias. This report reveals for the first time that the S-ICD is effective in reverting arrhythmias in ACM patients, even during exercise. Moreover, these cases may confirm that competition/physical activity is associated with ICD shocks

Electron acceleration in a JET disruption simulation

Runaways are suprathermal electrons having sufficiently high energy to be continuously accelerated up to tens of MeV by a driving electric field [1]. Highly energetic runaway electron (RE) beams capable of damaging the tokamak first wall can be observed after a plasma disruption [2]. Therefore, it is of primary importance to fully understand their generation mechanisms in order to design mitigation systems able to guarantee safe tokamak operations. In a previous work, [3], a test particle tracker was introduced in the JOREK 3D non-linear MHD code and used for studying the electron confinement during a simulated JET-like disruption. It was found in [3] that relativistic electrons are not completely deconfined by the stochastic magnetic field taking place during the disruption thermal quench (TQ). This is due to the reformation of closed magnetic surfaces at the beginning of the current quench (CQ). This result was obtained neglecting the inductive electric field in order to avoid the unrealistic particle acceleration which otherwise would have happened due to the absence of collision effects. The present paper extends [3] analysing test electron dynamics in the same simulated JET-like disruption using the complete electric field. For doing so, a simplified collision model is introduced in the particle tracker guiding center equations. We show that electrons at thermal energies can become RE during or promptly after the TQ due to a combination of three phenomena: a first REs acceleration during the TQ due to the presence of a complex MHD-induced electric field, particle reconfinement caused by the fast reformation of closed magnetic surfaces after the TQ and a secondary acceleration induced by the CQ electric field

The Tunisian traditional rabbit breeding system versus the commercial system: an epidemiological perspective

[EN] Rabbit breeding is practiced in many hot climate countries and contributes in terms of agricultural activities to rural development. In Tunisia two different rabbit breeding systems can be identified - the "traditional" (an integrated free range and underground system) and the "commercial" (employing sheds and wire net cages) practice. 24 Tunisian rabbitries (10 traditional and 14 commercial) were included in an epidemiological study aimed at comparing the prevalence of pathogenic bacteria responsible for upper respiratory and digestive diseases in the two breeding systems. A total of 128 adult rabbits (mean age of 9.4 months) were tested using deep nasal and rectal swabs. Symptoms of nasal discharge and/or diarrhea were recorded. 281 bacterial strains were isolated in total, 138 in commercial and 143 in traditional farms. The bacteria most frequently isolated (61.2%) were Gram-positive strains, which included Streptococcus sp. (22.8%), coagulase negative Staphylococcus sp. (17.8%) and coagulase-positive Staphylococcus (17.4%) strains. Among the Gram-negative isolated bacteria, Escherichia coli was the most frequent (12.5%), followed by Proteus sp. (5.7%). The two Salmonella strains isolated were Salmonella bongori (found in the commercial system), and Salmonella typhimurium definitive phage-type (DT) 104 (found in the traditional farming system). The absence of Pasteurella multocida in the list of isolated bacteria may be directly correlated to the method of conserving the samples (storage at freezing temperature). The coagulase-positive Staphylococcus strains were frequently isolated (73.5%) from healthy rabbits, but seldom from rabbits with rhinitis (18.4%) or diarrhea (8.2%). Staphylococcus aureus strains were recovered at a higher rate in commercial farms (21%) in comparison with traditional (11.9%) farms. However, this difference was not statistically significant. Four Staphylococcus aureus strains, all belonging to commercial farms, proved positive when tested for enterotoxin production. The antimicrobial susceptibility of isolated Staphylococcus aureus strains was also investigated. Most of the antibiotics tested were very effective: the highest level of susceptibility was observed with enrofloxacin (100%). The low performance of Tunisian traditional rabbit rearing has been linked to the high mortality rate, which may possibly be due to the increased presence of pathogens at the rabbit flock level. However, this was not confirmed by the results of our study due to the fact that the bacterial contamination seems to be comparable in both the traditional and the commercial breeding systems.Belli, P.; Fontana, E.; Sommariva, M.; Scarpelli, L.; Ricci, C.; Luzi, F.; Haddad, B. (2008). The Tunisian traditional rabbit breeding system versus the commercial system: an epidemiological perspective. World Rabbit Science. 16(4). doi:10.4995/wrs.2008.617SWORD16

Trans-arterial radioembolization in intermediate-advanced hepatocellular carcinoma: systematic review and meta-analyses.

Published onlineJournal ArticleThis is the final version of the article. Available from Impact Journals via the DOI in this record.Trans-arterial radioembolization (TARE) is a recognized, although not explicitly recommended, experimental therapy for unresectable hepatocellular carcinoma (HCC).A systematic literature review was performed to identify published studies on the use of TARE in intermediate and advanced stages HCC exploring the efficacy and safety of this innovative treatment.Twenty-one studies reporting data on overall survival (OS) and time to progression (TTP), were included in a meta-analysis. The pooled post-TARE OS was 63% (95% CI: 56-70%) and 27% (95% CI: 21-33%) at 1- and 3-years respectively in intermediate stage HCC, whereas OS was 37% (95% CI: 26-50%) and 13% (95% CI: 9-18%) at the same time intervals in patients with sufficient liver function (Child-Pugh A-B7) but with an advanced HCC because of the presence of portal vein thrombosis. When an intermediate and advanced case-mix was considered, OS was 58% (95% CI: 48-67%) and 17% (95% CI: 12-23%) at 1- and 3-years respectively. As for TTP, only four studies reported data: the observed progression probability was 56% (95% CI: 41-70%) and 73% (95% CI: 56-87%) at 1 and 2 years respectively. The safety analysis, focused on the risk of liver decompensation after TARE, revealed a great variability, from 0-1% to more than 36% events, influenced by the number of procedures, patient Child-Pugh stage and treatment duration.Evidence supporting the use of radioembolization in HCC is mainly based on retrospective and prospective cohort studies. Based on this evidence, until the results of the ongoing randomized trials become available, radioembolization appears to be a viable treatment option for intermediate-advanced stage HCC.The present study was funded by ASBM Srl through an unrestricted grant to CERGAS, Bocconi University, Via Roentgen 1, 20136 Milan, Italy

Fast Gibbs sampling for high-dimensional Bayesian inversion

Solving ill-posed inverse problems by Bayesian inference has recently attracted considerable attention. Compared to deterministic approaches, the probabilistic representation of the solution by the posterior distribution can be exploited to explore and quantify its uncertainties. In applications where the inverse solution is subject to further analysis procedures, this can be a significant advantage. Alongside theoretical progress, various new computational techniques allow to sample very high dimensional posterior distributions: In [Lucka2012], a Markov chain Monte Carlo (MCMC) posterior sampler was developed for linear inverse problems with $\ell_1$-type priors. In this article, we extend this single component Gibbs-type sampler to a wide range of priors used in Bayesian inversion, such as general $\ell_p^q$ priors with additional hard constraints. Besides a fast computation of the conditional, single component densities in an explicit, parameterized form, a fast, robust and exact sampling from these one-dimensional densities is key to obtain an efficient algorithm. We demonstrate that a generalization of slice sampling can utilize their specific structure for this task and illustrate the performance of the resulting slice-within-Gibbs samplers by different computed examples. These new samplers allow us to perform sample-based Bayesian inference in high-dimensional scenarios with certain priors for the first time, including the inversion of computed tomography (CT) data with the popular isotropic total variation (TV) prior.Comment: submitted to "Inverse Problems

Therapeutic Implications of Tumor Microenvironment in Lung Cancer: Focus on Immune Checkpoint Blockade

In the last decade, the treatment of non-small cell lung cancer (NSCLC) has been revolutionized by the introduction of immune checkpoint inhibitors (ICI) directed against programmed death protein 1 (PD-1) and its ligand (PD-L1), or cytotoxic T lymphocyte antigen 4 (CTLA-4). In spite of these improvements, some patients do not achieve any benefit from ICI, and inevitably develop resistance to therapy over time. Tumor microenvironment (TME) might influence response to immunotherapy due to its prominent role in the multiple interactions between neoplastic cells and the immune system. Studies investigating lung cancer from the perspective of TME pointed out a complex scenario where tumor angiogenesis, soluble factors, immune suppressive/regulatory elements and cells composing TME itself participate to tumor growth. In this review, we point out the current state of knowledge involving the relationship between tumor cells and the components of TME in NSCLC as well as their interactions with immunotherapy providing an update on novel predictors of benefit from currently employed ICI or new therapeutic targets of investigational agents. In first place, increasing evidence suggests that TME might represent a promising biomarker of sensitivity to ICI, based on the presence of immune-modulating cells, such as Treg, myeloid derived suppressor cells, and tumor associated macrophages, which are known to induce an immunosuppressive environment, poorly responsive to ICI. Consequently, multiple clinical studies have been designed to influence TME towards a pro-immunogenic state and subsequently improve the activity of ICI. Currently, the mostly employed approach relies on the association of \u201cclassic\u201d ICI targeting PD-1/PD-L1 and novel agents directed on molecules, such as LAG-3 and TIM-3. To date, some trials have already shown promising results, while a multitude of prospective studies are ongoing, and their results might significantly influence the future approach to cancer immunotherapy

Effects of acetylsalicylic acid on adiposity in a mouse model of diet-induced obesity

Obesity is a growing public health problem and its prevalence has reached epidemic proportions in recent decades [1]. Several studies have demonstrated that obesity modifies the metabolic and endocrine functions of adipose tissue and is closely associated with chronic, low grade inflammation [2]. Because inflammation was proposed to be involved in the pathophysiology of obesity [1,2], we decided to evaluate the effects of the antinflammatory drug acetylsalicylic acid (ASA) in a mouse model of diet-induced obesity. We performed the experiments using C57BL/6J female mice fed for three months with Standard Diet (SD) or with High Fat Diet (HFD). At the end of three months, mice fed with HFD were separated in four groups and fed for other two months as follows: one group continued with HFD, one group returned to SD, one group continued with HFD with the addition of 30mg/kg of ASA and, finally, the last group returned to SD with the addition of 30mg/kg of ASA. ASA was administered in the drinking water. The metabolic and inflammatory status was evaluated by histological, molecular and biochemical analysis in all mice. As expected, HFD induced an increase in body weight and insulin resistance with a consequent reduction of glucose tolerance. Measurement of adipocyte size revealed that ASA significantly reduced HFD-induced adipocyte hypertrophy and it was able to revert insulin resistance with amelioration of glucose tolerance. Moreover, gene expression profiles of pro- and anti-inflammatory cytokines as well as the expression of macrophage and lymphocyte markers showed that HFD led to a significant increase in macrophages accumulation and an increase of inflammatory cytokines. However, we observed a significant trend for reduction of these molecules after treatment with ASA. The level of the anti-inflammatory molecules were also significantly increased after ASA administration. In conclusion, our results suggest that ASA can be proposed as pharmacologic option for reducing adipose tissue inflammation associated with obesity

Calcium as a key player in arrhythmogenic cardiomiopathy : adhesion disorder or intracellular alteration?

Arrhythmogenic cardiomyopathy (ACM) is an inherited heart disease characterized by sudden death in young people and featured by fibro-adipose myocardium replacement, malignant arrhythmias, and heart failure. To date, no etiological therapies are available. Mutations in desmosomal genes cause abnormal mechanical coupling, trigger pro-apoptotic signaling pathways, and induce fibro-adipose replacement. Here, we discuss the hypothesis that the ACM causative mechanism involves a defect in the expression and/or activity of the cardiac Ca2+ handling machinery, focusing on the available data supporting this hypothesis. The Ca2+ toolkit is heavily remodeled in cardiomyocytes derived from a mouse model of ACM defective of the desmosomal protein plakophilin-2. Furthermore, ACM-related mutations were found in genes encoding for proteins involved in excitation\u2012contraction coupling, e.g., type 2 ryanodine receptor and phospholamban. As a consequence, the sarcoplasmic reticulum becomes more eager to release Ca2+, thereby inducing delayed afterdepolarizations and impairing cardiac contractility. These data are supported by preliminary observations from patient induced pluripotent stem-cell-derived cardiomyocytes. Assessing the involvement of Ca2+ signaling in the pathogenesis of ACM could be beneficial in the treatment of this life-threatening disease