Reduced lysosomal acid lipase activity: A new marker of liver disease severity across the clinical continuum of non-alcoholic fatty liver disease?

Lysosomal acid lipase (LAL) plays a key role in intracellular lipid metabolism. Reduced LAL activity promotes increased multi-organ lysosomal cholesterol ester storage, as observed in two recessive autosomal genetic diseases, Wolman disease and Cholesterol ester storage disease. Severe liver steatosis and accelerated liver fibrosis are common features in patients with genetic LAL deficiency. By contrast, few reliable data are available on the modulation of LAL activity in vivo and on the epigenetic and metabolic factors capable of regulating its activity in subjects without homozygous mutations of the Lipase A gene. In the last few years, a less severe and non-genetic reduction of LAL activity was reported in children and adults with non-alcoholic fatty liver disease (NAFLD), suggesting a possible role of LAL reduction in the pathogenesis and progression of the disease. Patients with NAFLD show a significant, progressive reduction of LAL activity from simple steatosis to non-alcoholic steatohepatitis and cryptogenic cirrhosis. Among cirrhosis of different etiologies, those with cryptogenic cirrhosis show the most significant reductions of LAL activity. These findings suggest that the modulation of LAL activity may become a possible new therapeutic target for patients with more advanced forms of NAFLD. Moreover, the measurement of LAL activity may represent a possible new marker of disease severity in this clinical setting

Surgical outcome after isolated on-pump and off-pump anterior descending coronary revascularisation.

PRINCIPLES: Anterior descending coronary revascularisation can be performed with or without cardiopulmonary bypass. We compared surgical outcomes and postoperative results of two groups of patients operated on for isolated anterior descending coronary revascularisation with the left internal mammary artery, in order to determine the ideal target patient of each technique. METHODS: From July 1997 to December 2012, 243 consecutive patients underwent off-pump (119) or on-pump (124) surgery for isolated revascularisation of the anterior descending coronary artery. We retrospectively collected, analysed and compared preoperative, intraoperative and postoperative variables. RESULTS: In the on-pump group, aortic cross-clamp and bypass times were 22 and 35 minutes, respectively. Mean surgical time was 126 minutes for the off-pump group and 160 minutes for the on-pump group. Off-pump patients were more often men (82% vs 66%, p = 0.006), older (median age 67 vs 64 years, p = 0.013), with renal failure (11% vs 2.4%, p = 0.009) and respiratory failure (20% vs 7.3%, p = 0.003), with peripheral vascular disease (17% vs 8%, p = 0.038) and affected by a higher degree of angina (p <0.001). Surgical time was shorter off-pump (p <0.001), but a greater number of urgent procedures were performed on-pump (11% vs 3.4%, p = 0.042). No difference in postoperative characteristics and complications except for the intensive care unit stay, which was shorter off-pump (median 1 vs 2 days, p = 0.046). Hospital mortality was 0.8% off-pump and 1.6% on-pump (p = 0.5). CONCLUSION: Both on-pump and off-pump surgery for isolated anterior descending coronary revascularization are safe with equal surgical risk. Off-pump procedures seem to be more appropriate in nonurgent patients with higher surgical risk profiles

The Fourth Positive System of Carbon Monoxide in the Hubble Space Telescope Spectra of Comets

The rich structure of the Fourth Positive System (A-X) of carbon monoxide accounts for many of the spectral features seen in long slit HST-STIS observations of comets 153P/Ikeya-Zhang, C/2001 Q4 (NEAT), and C/2000 WM1 (LINEAR), as well as in the HST-GHRS spectrum of comet C/1996 B2 Hyakutake. A detailed CO fluorescence model is developed to derive the CO abundances in these comets by simultaneously fitting all of the observed A-X bands. The model includes the latest values for the oscillator strengths and state parameters, and accounts for optical depth effects due to line overlap and self-absorption. The model fits yield radial profiles of CO column density that are consistent with a predominantly native source for all the comets observed by STIS. The derived CO abundances relative to water in these comets span a wide range, from 0.44% for C/2000 WM1 (LINEAR), 7.2% for 153P/Ikeya-Zhang, 8.8% for C/2001 Q4 (NEAT) to 20.9% for C/1996 B2 (Hyakutake). The subtraction of the CO spectral features using this model leads to the first identification of a molecular hydrogen line pumped by solar HI Lyman-beta longward of 1200A in the spectrum of comet 153P/Ikeya-Zhang. (Abridged)Comment: 12 pages, 11 figures, ApJ accepte

Managing chronic conditions: lessons learnt from a comparative analysis of seven years’ policies for chronic care patients in Italy

This policy paper aims to compare what policies are developed in Italy for the management of chronic patients in order to improve population health, quality of care and patient experience and reduce per-capita cost. The paper also aims to identify the key trends and evolutionary trajectories across the Country. Methodology: The analysis focuses on 10 Italian Regions and the time span of observation is 7 years (from 2014 to 2020). Data collection and analysis adopts mixed methods in order to have a more in-depth picture of the contextual factors, mechanisms and outcomes. It includes a desk research of the literature and documentary analysis; semi-structured interviews; a theory driven evaluation of 12 programmes identified at the regional level; and a Consensus Conference to discuss and validate the results with an Expert Panel Group. Conclusions: The paper firstly describes the main policies developed in Italy in the last seven years; secondly, it discusses six main trends and clusters them into three strategies: demand management strategies; strategies to improve the management of comorbid and frail patients; and strategies to improve the coordination between levels of care and the patient journey; thirdly, it discusses eight trends and evolutionary trajectories which are now emerging

Star formation properties of sub-mJy radio sources

We investigate the star formation properties of ~800 sources detected in one of the deepest radio surveys at 1.4 GHz. Our sample spans a wide redshift range (~0.1 - 4) and about four orders of magnitude in star formation rate (SFR). It includes both star forming galaxies (SFGs) and active galactic nuclei (AGNs), further divided into radio-quiet and radio-loud objects. We compare the SFR derived from the far infrared luminosity, as traced by Herschel, with the SFR computed from their radio emission. We find that the radio power is a good SFR tracer not only for pure SFGs but also in the host galaxies of RQ AGNs, with no significant deviation with redshift or specific SFR. Moreover, we quantify the contribution of the starburst activity in the SFGs population and the occurrence of AGNs in sources with different level of star formation. Finally we discuss the possibility of using deep radio survey as a tool to study the cosmic star formation history.Comment: 18 pages, 14 figures, 1 table (available in its entirety as ancillary data

Apparent high metallicity in 3-4 keV galaxy clusters: the inverse iron-bias in action in the case of the merging cluster Abell 2028

Recent work based on a global measurement of the ICM properties find evidence for an increase of the iron abundance in galaxy clusters with temperature around 2-4 keV up to a value about 3 times larger than that typical of very hot clusters. We have started a study of the metal distribution in these objects from the sample of Baumgartner et al. (2005), aiming at resolving spatially the metal content of the ICM. We report here on a 42ks XMM observation of the first object of the sample, the cluster Abell 2028. The XMM observation reveals a complex structure of the cluster over scale of 300 kpc, showing an interaction between two sub-clusters in cometary-like configurations. At the leading edges of the two substructures cold fronts have been detected. The core of the main subcluster is likely hosting a cool corona. We show that a one-component fit for this region returns a biased high metallicity. This inverse iron bias is due to the behavior of the fitting code in shaping the Fe-L complex. In presence of a multi-temperature structure of the ICM, the best-fit metallicity is artificially higher when the projected spectrum is modeled with a single temperature component and it is not related to the presence of both Fe-L and Fe-K emission lines in the spectrum. After accounting for the bias, the overall abundance of the cluster is consistent with the one typical of hotter, more massive clusters. We caution the interpretation of high abundances inferred when fitting a single thermal component to spectra derived from relatively large apertures in 3-4 keV clusters, because the inverse iron bias can be present. Most of the inferences trying to relate high abundances in 3-4 keV clusters to fundamental physical processes will likely have to be revised.Comment: 13 pages, 8 figures.Accepted for publication in Astronomy and Astrophysycs. Minor changes to match published versio

The Swift X-ray Telescope Cluster Survey II. X-ray spectral analysis

(Abridged) We present a spectral analysis of a new, flux-limited sample of 72 X-ray selected clusters of galaxies identified with the X-ray Telescope (XRT) on board the Swift satellite down to a flux limit of ~10-14 erg/s/cm2 (SWXCS, Tundo et al. 2012). We carry out a detailed X-ray spectral analysis with the twofold aim of measuring redshifts and characterizing the properties of the Intra-Cluster Medium (ICM). Optical counterparts and spectroscopic or photometric redshifts are obtained with a cross-correlation with NED. Additional photometric redshifts are computed with a dedicated follow-up program with the TNG and a cross-correlation with the SDSS. We also detect the iron emission lines in 35% of the sample, and hence obtain a robust measure of the X-ray redshift zX. We use zX whenever the optical redshift is not available. Finally, for all the sources with measured redshift, background-subtracted spectra are fitted with a mekal model. We perform extensive spectral simulations to derive an empirical formula to account for fitting bias. The bias-corrected values are then used to investigate the scaling properties of the X-ray observables. Overall, we are able to characterize the ICM of 46 sources. The sample is mostly constituted by clusters with temperatures between 3 and 10 keV, plus 14 low-mass clusters and groups with temperatures below 3 keV. The redshift distribution peaks around z~0.25 and extends up to z~1, with 60% of the sample at 0.1<z<0.4. We derive the Luminosity-Temperature relation for these 46 sources, finding good agreement with previous studies. The quality of the SWXCS sample is comparable to other samples available in the literature and obtained with much larger X-ray telescopes. Our results have interesting implications for the design of future X-ray survey telescopes, characterised by good-quality PSF over the entire field of view and low background.Comment: 27 pages, 15 figures; minor typos corrected. To be published in A&A, Volume 567, July 2014. Websites of the SWXCS project: http://www.arcetri.astro.it/SWXCS/ and http://swxcs.ustc.edu.cn

Experimental evaluation and modeling of physical hardening in asphalt binders

The research described in this paper deals with the experimental evaluation and modeling of physical hardening in asphalt binders. The term physical hardening refers to a reversible phenomenon occurring at low temperatures that causes time-dependent changes in viscoelastic properties. The experimental approach, followed to quantitatively assess physical hardening, was based on flexural creep tests carried out by means of the Bending Beam Rheometer at various temperatures and conditioning times. The results obtained confirmed that hardening phenomena have a significant influence on the creep response of asphalt binders, to an extent that can be quantitatively assessed by referring to the appropriate rheological parameters and by applying the loading time–conditioning time superposition principle. The experimental data were fitted to a mechanical model proposed in the literature (composed of a single Kelvin–Voigt element) and thereafter to an improved model (with two Kelvin–Voigt elements in series). Both models were assessed in terms of their prediction accuracy. The improved model was found to better describe physical hardening effects in the case of both short-and long-term conditioning. Practical implications of the study were finally highlighted by referring to possible ranking criteria to be introduced in acceptance procedures for the comparative evaluation of asphalt binders