PRM102 Budget Impact Analysis of Delayed-Release Dimethylfumarate In The Treatment of Relapsing-Remitting Multiple Sclerosis In Italy

INTRODUCTION: Multiple Sclerosis (MS) is a condition with a significant economic and social burden that affects young adults, in their active working phase. The most recent evaluations show an annual average social cost of € 38-39 thousand per patient. Today the approval of the new oral therapies allows physicians to select further options that can meet patients’ clinical unmet needs. OBJECTIVES: To evaluate the economic impact of a recently approved therapy, delayed-release dimethyl-fumarate (DMF; also known as gastro-resistant DMF), on the overall management costs of relapsing-remitting multiple sclerosis (RRMS) in Italy. METHODS: A budget impact model, adopting the perspective of the Italian National Healthcare Service (NHS), was used to compare healthcare costs of two different treatment scenarios: a) base-case, where DMF is not available for RRMS patients (Scenario A), vs. b) alternative-case, where DMF is available for RRMS patients (Scenario B). Healthcare costs sustained by the Italian NHS to manage the RRMS population (drug treatment, administration, therapy and disease monitoring, relapse management, treatment-related adverse events) have been calculated over 3 years and compared for the two scenarios. Impact of relapses for the disease modifying therapies (DMTs) included in the analysis was estimated using an elaboration of the results from published mixed treatment comparison. RRMS population treated with DMTs was estimated using Italian prevalence and incidence data. According to these estimates, the number of treated patients amounted to 36,078 at Year 1, 38,832 at Year 2, and 40,673 at Year 3. RESULTS: According to the current price and to the assumptions reported in the methodology section, it was estimated that the introduction of DMF (Scenario B) determines a decrease of the budget impact, if compared with the base case (Scenario A) in the perspective of Italian NHS. Over three years, the budget impact would be € 1,376 mln in the Scenario A and € 1,354 mln in the Scenario B (-22.18 mln €; -1.61% relative budget variation). The main drivers for cost-saving were pharmacological treatment costs and reduced burden of relapses (corresponding to more than 1,800 avoided relapses). CONCLUSIONS: At the current cost conditions applied in Italy and according to the described assumptions, the use of DMF is economically sustainable for the Italian NHS. Plausibly, the introduction and usage of this new therapy in RRMS patients will ensure clinical benefits for patients without resulting in additional costs for the Italian NHS. [In Italian

Compton-thick AGN in the NuSTAR era II: A deep NuSTAR and XMM-Newton view of the candidate Compton thick AGN in NGC 1358

We present the combined NuSTATR and XMM-Newton 0.6-79 keV spectral analysis of a Seyfert 2 galaxy, NGC 1358, which we selected as a candidate Compton thick (CT-) active galactic nucleus (AGN) on the basis of previous Swift/BAT and Chandra studies. According to our analysis, NGC 1358 is confirmed to be a CT-AGN using physical motivated models, at >3 $\sigma$ confidence level. Our best-fit shows that the column density along the 'line-of-sight' of the obscuring material surrounding the accreting super-massive black hole is N$\rm _H$ = [1.96--2.80] $\times$ 10$^{24}$ cm$^{-2}$. The high-quality data from NuSTAR gives the best constraints on the spectral shape above $\sim$10 keV to date on NGC 1358. Moreover, by combining NuSTAR and XMM-Newton data, we find that the obscuring torus has a low covering factor ($f_c$ <0.17), and the obscuring material is distributed in clumps, rather than uniformly. We also derive an estimate of NGC 1358's Eddington ratio, finding it to be $\lambda_{\rm Edd}$ $\sim$$4.7_{-0.3}^{+0.3}$ $\times$ 10$^{-2}$, which is in acceptable agreement with previous measurements. Finally, we find no evidence of short-term variability, over a $\sim$100 ks time-span, in terms of both 'line-of-sight' column density and flux.Comment: 12 pages, 6 figure

Inferring Compton-thick AGN candidates at z>2 with Chandra using the >8 keV restframe spectral curvature

To fully understand cosmic black hole growth we need to constrain the population of heavily obscured active galactic nuclei (AGN) at the peak of cosmic black hole growth ($z\sim$1-3). Sources with obscuring column densities higher than $\mathrm{10^{24}}$ atoms $\mathrm{cm^{-2}}$, called Compton-thick (CT) AGN, can be identified by excess X-ray emission at $\sim$20-30 keV, called the "Compton hump". We apply the recently developed Spectral Curvature (SC) method to high-redshift AGN (2<z<5) detected with Chandra. This method parametrizes the characteristic "Compton hump" feature cosmologically redshifted into the X-ray band at observed energies <10 keV. We find good agreement in CT AGN found using the SC method and bright sources fit using their full spectrum with X-ray spectroscopy. In the Chandra deep field south, we measure a CT fraction of $\mathrm{17^{+19}_{-11}\%}$ (3/17) for sources with observed luminosity $\mathrm{>5\times 10^{43}}$ erg $\mathrm{s^{-1}}$. In the Cosmological evolution survey (COSMOS), we find an observed CT fraction of $\mathrm{15^{+4}_{-3}\%}$ (40/272) or $\mathrm{32\pm11 \%}$ when corrected for the survey sensitivity. When comparing to low redshift AGN with similar X-ray luminosities, our results imply the CT AGN fraction is consistent with having no redshift evolution. Finally, we provide SC equations that can be used to find high-redshift CT AGN (z>1) for current (XMM-Newton) and future (eROSITA and ATHENA) X-ray missions.Comment: 10 pages, 8 figure

Petrogenesis of fertile mantle peridotites from the Monte del Estado massif (Southwest Puerto Rico): a preserved section of Proto-Caribbean lithospheric mantle?

The Monte del Estado massif is the largest and northernmost serpentinized peridotite belt in southwest Puerto Rico. It is mainly composed of spinel lherzolite and minor harzburgite with variable clinopyroxene modal abundances. Mineral and whole rock major and trace element compositions of peridotites coincide with those of fertile abyssal mantle rocks from mid ocean ridges. Peridotites lost 2-14 wt% of relative MgO and variable amounts of CaO by serpentinization and seafloor weathering. HREE contents in whole rock indicate that the Monte del Estado peridotites are residues after low to moderate degrees (2-15%) of fractional partial melting in the spinel stability field. However, very low LREE/HREE and MREE/HREE in clinopyroxene cannot be explained by melting models of a spinel lherzolite source and support that the Monte del Estado peridotites experienced initial low fractional melting degrees (~ 4%) in the garnet stability field. The relative enrichment of LREE in whole rock is not due to alteration processes but probably reflects the capture of percolating fluid/melt fractions or the crystallization of sub-percent amounts of hydrous minerals (e.g., amphibole, phlogopite) along grain boundaries or as microinclusions in minerals. We propose that the Monte del Estado peridotite belt represents a section of ancient Proto-Caribbean (Atlantic) lithospheric mantle originated by seafloor spreading between North and South America in the Late Jurassic- Early Cretaceous. This portion of oceanic lithospheric mantle was subsequently trapped in the forearc region of the Greater Antilles paleo-island arc generated by the northward subduction of the Caribbean plate beneath the Proto-Caribbean ocean. Finally, the Monte del Estado peridotites belt was emplaced in the Early Cretaceous probably as result of the change in subduction polarity of the Greater Antilles paleo-island arc without having been significantly modified by subduction processes

The prevalence and predictors of comorbid bipolar disorder and obsessive-compulsive disorder: A systematic review and meta-analysis

Abstract Background: Although some authors have recently investigated the co-occurrence of anxiety and bipolar disorders, the topic remains insufficiently studied. Defining the prevalence and predictors of BD-OCD comorbidity has important nosological, clinical and therapeutic implications. Methods: A systematic review and meta-analysis was conducted on the prevalence and predictors of comorbid BD-OCD. Relevant papers published through March 30th, 2015 were identified searching the electronic databases MEDLINE, Embase, PsycINFO and the Cochrane Library. Results: 46 articles met inclusion criteria. The pooled prevalence of OCD in BD was 17.0% (95% CI 12.7-22.4%), which was comparable to the results reported by the pooled prevalence of BD in OCD (18.35%, 95% CI 13.2-24.8%). With regard to OCD-BD predictors, a higher mean age predicted a lower prevalence of OCD in BD patients. Sub group meta-analyses reported higher OCD prevalence rates in BD children and adolescents (24.2%, compared to 13.5% in adults), in BD-I patients (24.6%, compared to 13.6% in mixed BD patients), and among population-based studies (22.2%, compared to 13.2% in hospital-based studies). Limitations: Most studies use retrospective assessment scales with low sensitivity in discriminating true ego-dystonic obsessions from depressive ruminations that may bias results towards an overestimation of obsessive symptom prevalence. Conclusions: This first systematic review and meta-analysis of the prevalence and predictors of comorbid BD-OCD confirms that BD-OCD comorbidity is a common condition in psychiatry with children and adolescents and BD-I patients as the most affected subgroups

Star-forming galaxies versus low- and high-excitation radio AGN in the VLA-COSMOS 3GHz Large Project

We study the composition of the faint radio population selected from the VLA-COSMOS 3GHz Large Project, a radio continuum survey performed at 10 cm wavelength. The survey covers the full 2 square degree COSMOS field with mean $rms\sim2.3$ $\mu$Jy/beam, cataloging 10,899 source components above $5\times rms$. By combining these radio data with UltraVISTA, optical, near-infrared, and Spitzer/IRAC mid-infrared data, as well as X-ray data from the Chandra Legacy, and Chandra COSMOS surveys, we gain insight into the emission mechanisms within our radio sources out to redshifts of $z\sim5$. From these emission characteristics we classify our souces as star forming galaxies or AGN. Using their multi-wavelength properties we further separate the AGN into sub-samples dominated by radiatively efficient and inefficient AGN, often referred to as high- and low-excitation emission line AGN. We compare our method with other results based on fitting of the sources' spectral energy distributions using both galaxy and AGN spectral models, and those based on the infrared-radio correlation. We study the fractional contributions of these sub-populations down to radio flux levels of $\sim$10 $\mu$Jy. We find that at 3 GHz flux densities above $\sim$400 $\mu$Jy quiescent, red galaxies, consistent with the low-excitation radio AGN class constitute the dominant fraction. Below densities of $\sim$200 $\mu$Jy star-forming galaxies begin to constitute the largest fraction, followed by the low-excitation, and X-ray- and IR-identified high-excitation radio AGN.Comment: 7 pages, 3 figures, The many facets of extragalactic radio surveys: towards new scientific challenges, Bologna 20-23 October 201

Enhancement of the luminescence properties of Eu (III) containing paramagnetic saponite clays

In this study, 1,10-phenanthroline molecules were introduced in the interlayer space of a paramagnetic synthetic saponite clay containing both Eu3+ and Gd3+ ions in structural positions. Two samples with different loading of phenanthroline dye were prepared. The resulting hybrid materials possessed improved optical emission properties due to an efficient antenna effect from the phenanthroline to the Eu3+ centers; this effect was demonstrated to be higher than the metal-to-metal Gd3+-Eu3+ energy transfer previously studied. Insights on the relaxometric properties in aqueous solution of the solids after incorporation of the antenna groups were also obtained through NMR relaxometric analyses

Oxygen doping-induced photogeneration loss in P3HT:PCBM solar cells

This work investigates the loss in performance induced by molecular oxygen in bulk heterojunction solar cells. We observe that upon exposure to molecular oxygen both formation of P3HT+:O2− complex and metal oxidation at the interface between the active layer and metallic contact occur. These two different effects were separately investigated using NOBF4 as an oxidant. Our procedure has allowed studying p-doping of the active layer independently from contact degradation. A loss in photocurrent is associated with formation of P3HT+:O2− complex, which reduces the concentration of neutral P3HT present in the film in accordance with absorption and external quantum efficiency spectra. This complex is regarded as a source of a pathway of reversible degradation. Capacitance–voltage measurements allow for an accurate extraction of p-doping levels of the active layer produced by the presence of charged O2− species. In addition, one of the irreversible degradation pathways is identified to be oxidation of the metallic contact to form CaO. This oxide forms a thin dipole layer producing a voltage drop across the active layer/Ca interface, which has a direct impact on the open circuit voltage and fill factor

Resolving the cosmic X-ray background with a next-generation high-energy X-ray observatory

The cosmic X-ray background (CXB), which peaks at an energy of ~30 keV, is produced primarily by emission from accreting supermassive black holes (SMBHs). The CXB therefore serves as a constraint on the integrated SMBH growth in the Universe and the accretion physics and obscuration in active galactic nuclei (AGNs). This paper gives an overview of recent progress in understanding the high-energy (>~10 keV) X-ray emission from AGNs and the synthesis of the CXB, with an emphasis on results from NASA's NuSTAR hard X-ray mission. We then discuss remaining challenges and open questions regarding the nature of AGN obscuration and AGN physics. Finally, we highlight the exciting opportunities for a next-generation, high-resolution hard X-ray mission to achieve the long-standing goal of resolving and characterizing the vast majority of the accreting SMBHs that produce the CXB.Comment: Science White paper submitted to Astro2020 Decadal Survey; 5 pages, 3 figures, plus references and cover pag