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Nowadays, the circularity concept dominates the debate on resource management in cities and territories. The idea is often used as a vehicle towards a more sustainable socio-ecological transition, based on the circular economy (CE) framework. Unlike other sustainability frameworks, CE originates in ecological and environmental economics and industrial ecology. It focuses on developing an alternative economic and technological model for production and consumption, avoiding natural resource depletion and redesigning processes and cycles of materials (closed-loops). However, when CE is translated to cities and territories, its environmental, economic and design agency is often neglected. On the one hand, it demands to acknowledge the need for a relational understanding of space, place and actors involved and, on the other, to explore the spatial specificity of CE. Therefore, there is a need for a broader theoretical discourse on the CE’s territoriality as the predominant. Research on circular urban and territorial development demands more than merely upscaling industrial ecosystems diagrams and generating circular businesses. Consequently, what is the role of territory in the CE conceptualisation in the urbanism literature? How to interpret territories through the lens of circularity, which tools, methods are needed? Therefore, territory, its role and meaning in the CE contribution to urban regeneration is the key focus of this text.

The aim of this study is to provide updates on the characteristics of chronic HBsAg carriers in Italy before the advent of new drugs eliminating or functionally inactivating the genome HBV reservoirs. HBV endemicity has greatly decreased in Italy over the past decades. A not negligible number of chronic HBsAg carriers are still alive in the country. Chronic HBsAg carriers consecutively referring to 9units in Italy were prospectively enrolled for a 6-month period in 2019. Multiple logistic regression analysis was performed to identify independent predictors of treatment. A total of 894 cases was recruited (sex ratio 1.6; mean age 53.7 ± 13.5years). The proportion of subjects born abroad was 19.0%; only 1% of cases reported current heavy alcohol intake (> 4 units/day). Chronic HBV infection, chronic HBV hepatitis, and subjects with liver cirrhosis and/or HCC represented 24.8%, 55%, and 19.3% of cases, respectively. After exclusion of the 222 subjects with chronic HBV infection, the proportion of subjects under therapy was as high as 89.3%. A more severe liver disease (OR 2.52; 95% CI = 1.25–5.14) resulted an independent predictor of the likelihood of treatment; male sex was marginally associated (OR 1.67; 95% CI = 1.02–2.76) to the chance of treatment. People born abroad had same chance than Italians native to be treated (OR 2.12; 95% CI = 0.9–4.97). The high proportion of subjects under treatment and the absence of gender and ethnic barrier against treatment sound good news. These updated figures may represent reference data for evaluating the potential impact of forthcoming new therapy against HBV-related disease.

Background Patients with coronavirus disease 2019 (Covid-19) may experience venous thrombosis while data regarding arterial thrombosis are sparse. Methods Prospective multicenter study in 5 hospitals including 373 patients with Covid-19-related pneumonia. Demographic data, laboratory findings including coagulation tests and comorbidities were reported. During the follow-up any arterial or venous thrombotic events and death were registered. Results Among 373 patients, 75 (20%) had a thrombotic event and 75 (20%) died. Thrombotic events included 41 venous thromboembolism and 34 arterial thrombosis. Age, cardiovascular disease, intensive care unit treatment, white blood cells, D-dimer, albumin and troponin blood levels were associated with thrombotic events. In a multivariable regression logistic model, intensive care unit treatment (Odds Ratio [OR]: 6.0; 95% Confidence Interval [CI] 2.8–12.6; p p = 0.022); and albumin levels (OR: 0.49; 95% CI 0.28–0.87; p = 0.014) were associated with ischemic events. Age, sex, chronic obstructive pulmonary disease, diabetes, heart failure, coronary heart disease, intensive care unit treatment, in-hospital thrombotic events, D-dimer, C-reactive protein, troponin, and albumin levels were associated with mortality. A multivariable Cox regression analysis showed that in-hospital thrombotic events (hazard ratio [HR]: 2.72; 95% CI 1.59–4.65; p p = 0.001), and albumin (HR: 0.447; 95% CI 0.277–0.723; p = 0.001) predicted morality. Conclusions Covid-19 patients experience an equipollent rate of venous and arterial thrombotic events, that are associated with poor survival. Early identification and appropriate treatment of Covid-19 patients at risk of thrombosis may improve prognosis.

Introduction: The Guidelines recommend to perform the Blood Gas Analysis (BGA) only when there is a risk of hypoxia. The aim of this study is to investigate whether there would be missing cases of pathological neonates within a population who is defined to be low risk until birth, for whom routine BGA is not recommended. Materials and methods: A cross sectional study including 3038 low risk women, allocated into the Normal Birth Group (NB Group) when normal labour and birth occurred, or into the Complicated Birth Group (CB Group) when some complications or interventions happened. Groups were compared using T-test and Chi-square. A two sided 5% significance level was adopted. Results: A significant difference between groups was found in pathological BGA (P < 0.000) and Apgar score

Fundamental changes in the societal use of biophysical resources are required for a sustainable transformation. Current (urban) metabolism research traces flows of energy and materials and products to capture resource use along valuechains from resource extraction to production and consumption and the discharge of wastes and emissions. However, spatial relation, local carrying capacity and qualitative characteristics of the urban landscape are only featured in very few studies, even if they are becoming crucial elements towards future sustainable development. Simultaneously, spatial studies tend to neglect the dimension of processes of flows and the generated stocks that influence the construction and performance of space. Big data and GIS technologies have thepotential to leverage the integration between the two fields of knowledge. Therefore, the article explores the development of an innovative method - Activity-based Spatial Material Flow Analysis -that integrates qualitative and quantitative flow specifications in material content and geographical space, starting from the analysis of waste flows relative to the Amsterdam Metropolitan Area (NL). Lastly, the article reflects on the results of the application of the AS-MFA method, namely a series of flow maps. Each flow map is a significant data-based network representation of a part of the urban metabolism within the AMA in a specific period of time.

Background Management of chronic hepatitis C (CHC) has significantly accelerated in the last few years. Currently, second generation direct acting antivirals (DAAs) promise clearance of infection in most of patients. Here we present the results of the first analysis carried out on data of Lazio clinical network for DAAs. Methods The study was designed as a multicenter cohort: a) to assess the evolution of treatment during the first 24 months of the activity of the Clinical Network; b) to report overall efficacy of treatments; c) to analyze potential factors associated with lack of virological response at 12 weeks after therapy (SVR12); d) to evaluate the variation of ALT at baseline and 12 weeks after therapy in those who achieved SVR12 in comparison to those who did not. Analyses of efficacy were carried out with multilevel mixed effect logistic regression model. ALT temporal variation was assessed by mixed effect model mixed models with random intercept at patient’s level and random slope at the level of the time; i.e. either before or after therapy. Results Between 30 December 2014 and 31 December 2016 5279 patients started a DAA treatment; of those, 5127 (in 14 clinical centers) had completed the 12-week follow-up. Overall proportion of SVR12 was 93.41% (N = 4780) with no heterogeneity between the 14 clinical centers. Interruption as the consequence of severe side effect was very low (only 23 patients). Unadjusted analysis indicates that proportion of SVR12 significantly changes according to patient’s baseline characteristics, however after adjusting for potential confounders only adherence to current guidelines, stage of liver diseases, gender, transplant and HIV status were independently associated with the response to therapy. Analysis of ALT temporal variation showed that ALT level normalized in most, but not, all patients who achieved SVR12. Conclusion Our study confirmed the extraordinary efficacy of DAAs outside clinical trials. The advantage of DAAs was particularly significant for those patients who were previously considered as difficult-to-treat and did not have treatment options before DAAs era. Intervention based on network of select centers and prioritization of patients according to diseases severity was successful. Further studies are needed to establish whether clearance of HCV after DAAs therapy can arrest or even revert liver fibrosis in non-cirrhotic patients and/or improve life quality and expectancy in those who achieve SVR12 with cirrhosis.

‘The land, so heavily charged with traces and with past readings, seems very similar to a palimpsest’ (Corboz 1985: 190). Any territory is the result of multiple and simultaneous processes; some are taking place spontaneously, others as the direct result of human interventions. (Secchi 1990; Secchi and Viganò 2009) For urbanists, a territory is a constructed physical and mental entity, where several socio-economic and cultural processes generated a juxtaposition of urban elements that at first sight seem to lack any coherence (De Meulder 2008). Nevertheless, a closer look allows an understanding into the ordering logics that determine through time the continuous production and reproduction of space (Harvey 2001). These logics are embodied in the territory itself, making it comparable to a ‘palimpsest’, in which the traces of recent and ancient modifications ‘lie’ (Corboz 1985: 190). As Vittoria Di Palma suggests, each action on the territory, either good or bad, leaves traces and ‘we cannot wish them away’ (Di Palma 2014: 01). Wasteland, in the form of abandoned built and un-built spaces, can also be seen as the remains of ancient transformation (Furlan 2017). An a posteriori mapping observation of these remains, as latent elements being temporarily unable to undergo transformation, allows us to understand what resists the flow of time, as well as what adapts or opposes itself to it (Viganò 2013). The presence of these traces can then be interpreted as signs of change. Consequently, mapping today’s wastelands is instrumental to unfolding historical landscape in transformation throughout a thick description in time and space. Considering the landscape as a dynamic entity whose spatial features are permanently emerging and constantly undergoing modification (De Meulder 2008:29), it is important to assume that the processes of transformation are grounded in a given space in ways that are both geographically and historically specific. Therefore, this chapter proposes to illustrate and test a thick mapping description through the case study of Charleroi’s post-industrial landscape. The region of Charleroi is situated in the centre of Belgium and was historically manipulated to accommodate first coal-mine, glass and steel industries and then the wasteland generated by the shrinking industry (Fig. 1). Investigating Charleroi’s wastelands and related landscape gives a unique opportunity to explore thick mapping as an approach to unfolding cultural context and meaning of historical landscape in transformation.

OBJECTIVES: This study aims to evaluate the reliability and clinical utility of NS3 sequencing in hepatitis C virus (HCV) 1-infected patients who were candidates to start a PI-containing regimen. METHODS: NS3 protease sequencing was performed by in-house-developed HCV-1 subtype-specific protocols. Phylogenetic analysis was used to test sequencing reliability and concordance with previous genotype/subtype assignment by commercial genotyping assays. RESULTS: Five hundred and sixty-seven HCV plasma samples with quantifiable HCV-RNA from 326 HCV-infected patients were collected between 2011 and 2014. Overall, the success rate of NS3 sequencing was 88.9%. The success rate between the two subtype protocols (HCV-1a/HCV-1b) was similarly high for samples with HCV-RNA >3 log IU/mL (>92% success rate), while it was slightly lower for HCV-1a samples with HCV-RNA ≤3 log IU/mL compared with HCV-1b samples. Phylogenetic analysis confirmed the genotype/subtype given by commercial genotyping assays in 92.9% (303/326) of cases analysed. In the remaining 23 cases (7.1%), 1 was HCV-1g (previously defined as subtype 1a), 1 was HCV-4d (previously defined as genotype 1b) and 1 was HCV-1b (previously defined as genotype 2a/2c). In the other cases, NS3 sequencing precisely resolved the either previous undetermined/discordant subtype 1 or double genotype/subtype assignment by commercial genotyping assays. Resistance-associated variants (RAVs) to PI were detected in 31.0% of samples. This prevalence changed according to PI experience (17.1% in PI-naive patients versus 79.2% in boceprevir/telaprevir/simeprevir-failing patients). Among 96 patients with available virological outcome following boceprevir/telaprevir treatment, a trend of association between baseline NS3 RAVs and virological failure was observed (particularly for HCV-1a-infected patients: 3/21 failing patients versus 0/22 achieving sustained virological response; P = 0.11). CONCLUSIONS: HCV-NS3 sequencing provides reliable results and at the same time gives two clinically relevant pieces of information: a correct subtype/genotype assignment and the detection of variants that may interfere with the efficacy of PI.

Purpose: To assess the contribution of Italian radiation oncologists in the current management of recurrent high-grade gliomas (HGG), focusing on a reirradiation (reRT) approach. Methods: In 2015, the Reirradiation and the Central Nervous System Study Groups on behalf of the Italian Association of Radiation Oncology (AIRO) proposed a survey. All Italian radiation oncologists were individually invited to complete an online questionnaire regarding their clinical management of recurrent HGG, focusing on a reRT approach. Results: A total of 37 of 210 questionnaires were returned (18% of all centers): 16 (43%) from nonacademic hospitals, 14 (38%) from academic hospitals, 5 (13%) from private institutions, and 2 (6%) from hadron therapy centers. The majority of responding centers (59%) treated ≤5 cases per year. Performance status at the time of recurrence, along with a target diameter Conclusions: Although there were wide variations in the clinical practice of reRT across the 37 centers, the core activities were reasonably consistent. These findings provide a basis for encouraging a national collaborative study to develop, implement, and monitor the use of reRT in this challenging clinical setting.

Deliverable 3.3 of Work Package 3 concerns an integrated analysis of the two pilot case studies within the REPAiR project, Amsterdam and Naples, from the vantage point of waste production and processing, and the transition to circular societies. It comprises spatial, social and material flow analyses of the two pilot cases, whilst testing an innovative methodology that was introduced and explained in Deliverable 3.1 [D3.1, AKA the Handbook, Geldermans et al., 2017]. The report addresses additions and clarifications to the methodology presented in Deliverable 3.1. After an update on the basis of technical insights and the work developed in practice within the peri-urban living labs (PULL) workshops carried out so far, an improved classification of Wastescapes is presented. Furthermore, a complete process model to map Wastescapes is provided. A smaller scale of the 'sample' area has been introduced to allow a better interaction with the local stakeholders, deepening the context and cutting into the intermediate scale of the ‘focus-area’. Moreover, the notion of Enabling Contexts is applied to rationalise the links between spatial analysis and eco-innovation solutions (WP5). With regard to the Material Flow Analysis, new insights on data collection and processing are addressed, providing more grip on how to successfully conduct such an MFA. The lion’s share of the report is allocated to presenting the results. For both cases, a rudimentary spatial and socio-economic analysis on a national level precedes a detailed regional analysis: for the Netherlands, this concerns the Amsterdam Metropolitan Area, and for Italy the Campania Region and the Metropolitan region of Naples. Embedded in this spatial-social context, the material flow analysis follows six Activity-based Spatial MFA (as introduced in D3.1) steps to pinpoint and analyse waste related challenges and activities. The report finishes with a reflection on the methodology and results. This reflection focuses on four topics in particular: physico-geographical aspects and waste-sensitivity, Waste(scape) dynamics in space & time, modelling of material flows & data intensity, and the relevance of Enabling Contexts, whilst anticipating the follow up cases as well as a wider field of application.

The territory is the result of several and simultaneous process of transformations, that independently from intensity and quality leave behind some traces. An a posteriori observation of these remains as inert and latent spaces in the territory enables the comprehension of what resists to the flow of time, what adapts or opposes itself to it. Therefore, this paper is based on idea of study the transformation of the territory, by observing the present situation, in which past and future converge. Reading the metamorphosis of the Charleroi region, by starting from the observation of the signs left on the territory is not a linear process. In less than a century, indeed, Charleroi region has been strongly manipulated to host the mining, glass and steel industries. Only after the second world war the long decline of this territory begun. Several successive phases of transformation and the decline of the mining, glass and steel industries have radically changed Charleroi’s territory, leaving a legacy of different levels of abandoned spaces. However, sixty years of abandonment slowly and silently changed these spaces, allowing the infiltration of ruderal vegetation, new form of appropriation and consequently supposing the beginning of a new life cycle for the region. In order to address this issue, the paper is divided in two main parts. In the first part the article briefly reconstructs the transformations of the industrial productions of Charleroi starting from the traces left on the territory. Finally, the second part aims to observe these traces from an ecological perspective, highlighting a different value.

Background: La letteratura propone il travaglio prolungato come fattore di rischio per l’emorragia post partum (EPP), tuttavia questa non definisce la durata dei singoli stadi in relazione all’outcome indagato. Questa revisione della letteratura ha come obiettivo primario quello di valutare la presenza di una correlazione tra durata dei singoli stadi del travaglio e rischio di EPP. Obiettivo secondario è determinare i cut off relativi ad ogni stadio, oltre i quali aumenta il rischio di EPP. Metodi: gli articoli sono stati reperiti da Pubmed e CINAHL in febbraio 2016. Gli studi inclusi riportavano la definizione di EPP e della durata degli stadi. Risultati: dalla revisione della letteratura è emerso che c’è correlazione tra la durata dei singoli stadi e l’EPP ma non si identifica un cut off comune tra gli studi. Discussione: gli studi inclusi non permettono di stabilire un limite temporale comune per ogni stadio in quanto il campione di ogni studio ha caratteristiche differenti (parità, tipo di parto, età gestazionale, insorgenza del travaglio, utilizzo dell’epidurale); inoltre gli studi non descrivono le singole fasi di ogni stadio. Background: literature show s that prolonged labour is a risk factor for the postpartum haemorrhage (HPP); although studies don’t define the specific stage associated with HPP. This literature review was conducted to evaluate evidence for the influence of each stage on the risk of HPP; and eventually, to define temporary cut off beyond whom there is an increase of HPP. Methods: articles w here searched using P ubmed and CI NAHL in February 2016. Studies w ere included according to 2 criteria: definition of HPP and length of each stage. Results: our literature review found evidence of association betw een the length of each stage and HPP; however, the literature review is not able to define a shared cut for each stage. Discussion: included studies don’t allow to define a unique cut off due to the heterogeneity of sample (parity, delivery, gestational age, onset of labor, use of epidural analgesia); moreover, the studies don’t evaluate the single phases of each stage.

Background: The prevalence of hepatitis C virus infection increases with advancing age, but elderly hepatitis C virus patients remain an understudied population. Aim: To define the virological, epidemiological and clinical profiles of Italian outpatients aged 65 years and over infected by hepatitis C virus. Methods: We evaluated 1544 anti-hepatitis C virus positive patients aged >=65 years referred to 34 Italian outpatient specialty clinics over a two-year period. Results: The study population included 1134 (73%) early elderly (65-74 years) and 410 (27%) late elderly patients (>=75 years). Late elderly subjects were less likely to have their virus genotyped, their viral load assessed or a histological evaluation of liver disease. Overall, 30% of patients had advanced liver disease whose prevalence increased with increasing age. In both age groups, about 40% of patients had normal transaminase levels. Excluding patients with past infection, 51% had not received any antiviral treatment and only 25% were treated after the age of 65. Late elderly patients, women and patients with advanced liver diseases had been less frequently treated. The main reason for exclusion from treatment was age followed by the presence of comorbid conditions. Conclusions: Elderly hepatitis C virus patients referred to Italian specialty clinics have advanced and underestimated liver disease. Nevertheless, they are progressively understudied in parallel with increasing age. © 2012 Editrice Gastroenterologica Italiana S.r.l.

BACKGROUND: Grape juice consumption may prevent several chronic diseases owing to the presence of phenolic compounds, which have an important role in the reduction of oxidative stress. This study investigated the polyphenol content and antioxidant activities of grape juices from two cultivars: BRS-Cora and Isabella. Total polyphenol content (TPC), anthocyanins, antioxidant capacity (oxygenradical absorbance capacity, ferric reducing antioxidantpower and1,1-diphenyl-2-picrylhydrazyl), and phenolic profile (high-performance liquid chromatography with diode array and fluorescence detection ? HPLC-DAD-FLD) were determined. RESULTS: BRS-Cora grape juice showed higher concentrations of total polyphenols and anthocyanins, as well as higher antioxidant potential, than those of Isabella grape juice. A significant positive correlation was found in TPC or anthocyanin contents when correlated with the remaining antioxidant assays. In addition, HPLC-DAD-FLD showed a higher total phenolic content in BRS-Cora grape juice compared to Isabella. CONCLUSION: The present results showBRS-Cora as a promising cultivar for grape juice production with an improved functional potential. Keywords: Isabella grape; BRS-Cora grape; grape juice; polyphenols; antioxidant potential; bioactive compounds Made available in DSpace on 2022-02-01T12:00:27Z (GMT). No. of bitstreams: 1 Silva-et-al-2016-Journal-of-the-Science-of-Food-and-Agriculture.pdf: 241644 bytes, checksum: 671d4fa599b8ee16413741469d86ab73 (MD5) Previous issue date: 2016

After attending this presentation, attendees will understand some principles of investigation of a dismembered body concerning the cause of death and the identification of the tools used to separate arms and legs from the trunk. This presentation will impact the forensic community by suggesting a novel approach for the analysis of cutting crimes in general and dismembering in particular. Herein investigators present the case of a 40-year-old female killed by throat cutting and consequently dismembered. She was found cut into 30 pieces inside three plastic bags in a garage. Dismemberment is the act of cutting, tearing, pulling, wrenching, or otherwise removing the limbs from the trunk of a living or deceased object. It may be practiced upon human beings as a form of capital punishment, a result of a traumatic accident, or in connection with murder, suicide, or cannibalism. After killing the victim, the murderer uses a very sharp cutting weapon (a saw, knife, axe, etc.) to sever the limbs and cut the body into pieces. The operation is generally carried out immediately after the crime, although more rarely a long time may pass between the two events. There are two types of dismemberment that are commonly seen: localized, such as the removal of the head or hands in an attempt to hinder identification of the victim, or generalized at multiple sites (commonly bisection of limbs or disarticulation of the joints) to aid in the disposal of the body. In these cases a new pattern of investigation must support classical techniques to solve the following forensic issues: - The evaluation of the time since death and of the time since dismemberment. Indeed, exsanguinations and dismemberment of the body prevent an accurate evaluation of lividities and rigidity. - The identification of the tools used to cut the body. Careful, thorough investigation is a key point to ensure that potential physical evidence is not tainted or destroyed. In particular it is essential to identify any potential sharp cutting weapons at the crime scene. Moreover, when saws are used to cut the body, characteristic tool marks are left on the bone. The nature of the marks depends on the size, shape, width of the saw, and on the sawing action of the user. Environmental Scanning Electron Microscopy (ESEM) may help in identifying the specific saw that has been used in the act of dismemberment. ESEM can detect and measure different types of striations, paint traces (such as rust inhibitor paints) or metal residues remaining on the bone after the cutting. In the case presented, the determination of potassium levels in the vitreous humour and their time changes showed that the victim had been killed 20 – 25 hours before the death scene investigation. The absence of lividities combined to histological and immunohistochemical investigation of the skin let investigators classify the dismembering injuries as non-vital wounds and to estimate the time interval between the death and the dismembering. However, the most interesting finding was the identification of the tools used to cut the soft tissues and the bones of the victim. Morphological and morphometrical analysis of the skin lesions pointed out that the arms and the legs were cut with a sharp knife, whereas the head was removed from the trunk by a woodworker saw. ESEM analysis determined that the bone injuries were produced by a particular type of saw covered by rust-inhibitor paint.

Grapes are important sources of antioxidants compounds and one of the most used varieties to elaborate juices is 'Isabel', or 'Isabella', as it is called in North-America. This study aimed to evaluate the antioxidant activity of Isabella grape juices from the tropical semi-arid climate produced in Brazil on March and September, 2010. Total phenolics and anthocyanins were determined, as well as the antioxidant capacity by DPPH, FRAP and hydrophilic ORAC methods. Test T was used to compare statistical difference at 5% of significance level. As expected, the results showed that the season can play a significant role on phenolics content and antioxidant power. Polyphenols content in juices varied from 82.9 ± 0.92 to 102.2 ± 1.59 mg GAE 100 mL-1 and anthocyanins content ranged from 44.3 ± 2.01 to 129.5 ± 2.82 mg cyanidin-3-glucoside 100 mL-1. Regression analyses showed a high correlation of antioxidant capacity and anthocyanins content. Grapes from Sao Francisco River Valley demonstrated to be a good source of antioxidant for human diet. Made available in DSpace on 2016-02-23T06:39:10Z (GMT). No. of bitstreams: 1 CASARINJFoodSciEngv3n2p642013.pdf: 165761 bytes, checksum: 52872d85a681de344f7c6fb7ca245734 (MD5) Previous issue date: 2013-04-19

Sodium phosphate enemas and laxatives are widely used for the treatment of constipation, even if a number of cases of significant toxicity due to alterations of the fluid and electrolyte equilibria (hypernatremia, hyperphosphatemia, and hypocalcemia) have been reported. We present the case of an 83-year-old man who died of fecal and chemical peritonitis secondary to an iatrogenic colon perforation (produced performing a Fleet enema through the patient's iliac colostomy) with peritoneal absorption of sodium phosphate. Environmental scanning electron microscopy coupled with an X-ray fluorescence energy dispersive spectrometry discovered multiple bright crystals formed of calcium, phosphorus, and oxygen in the brain, heart, lung, and kidney sections of the victim. The absence of these kinds of precipitates in two control samples chronically treated with Fleet enemas led us to assume that the deceased had adsorbed a great quantity of phosphorus ions from the peritoneal cavity with subsequent systemic dissemination and precipitation of calcium phosphate bindings.

Background. Bone diseases such as osteoporosis lead to changes in the trabecular bone mass and architecture. Improved methods for the quantitative assessment of trabecular bone are needed to better understand the role of trabecular architecture in bone strength. MR microscopy (MRM),'with its ability to achieve resolutions below 50 micromol has proved to be particularlyuseful for the ex vivo evaluation of the complex archi- tecture oftrabecular bone. In this study, we describe the use of projection reconstruction (PR) with MRM for the quantitative evaluation of the three-dimensional structure of trabecular bone explants and for the predictionof their biomechanical properties. Material and methods. High-resolution 3D PR and trabecular bone explants were analysed to determine standard morphologic parameters such as trabecular bone volume fraction (BV/TVor Vv), trabecular thick- ness (Tb.Th) and trabecular separation (Tb.Sp). Segmentation of the high-resolution images into bone and bone marrow was obtained by using a Bayesian approach. The derived parameters were finallyincluded in non-linear mathematical models for the prediction of Young's modulus (YM). Results. The parameters derived from the PR spin-echo were found to be stronger predictor of YM (RZ = 0.86) than those derived from the conventional spinecho images (R2 = 0.75) used for comparison. Conclusions.This ex vivo approach should be readily adaptable to the studies in human subjects. Izhodišča. Kostne bolezni, kot je osteoporoza, vodijo v spremembe trabekularnemase in arhitekture kosti, Za boljše razumevanje trabekularne strukture in kostne moči potrebujemo izboljšane kvantitativne metode. MR mikroskopija (MRM) se je s svojo zmožnostjo doseči resolucijo pod 50 microm izkazala za zelo uporabno pri ex vivo oceni kompleksne arhitekture trabekularnih kosti. V pričujoči študiji opisujemo uporabo projekcijske rekonstrukcije (PR) z MRM pri kvantitativni oceni tridimenzionalne trabekularne strukture kostnih eksplantatov in pri napovedovanju njihovih biomehaničnih značilnosti. Material in metode. Analizirali smo 3D PR visoke ločljivosti in eksplantate trabekularnih kosti, da bi določili standardne morfološke parametre kot so volumska frakcija trabekularne kosti, debelina trabekul in trabekularna separacija. Razločevanje slik visoke ločljivosti na kost in na kostni mozeg smo opravili z uporabo "Bayesianskega" pristopa. Pridobljene parametre smo na koncu vključili v nelinearen matematični model zadoločitev Youngovega modula (YM). Rezultati. Ugotovili smo, da so parametri,ki smo jih dobili pri spinskem odboju PR močnejši napovedovalci Youngovega modula (R2 = 0.86) kot parametri pridobljeni z konvencionalnimi spinskimi odbojnimi slikami (R2= 0.75), ki smo jih uporabljali za primerjavo. Zaključki. Opisani ex vivo pristop bi lahko zlahka prilagodili in vivo študijam.

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-26T23:55:09Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:33:08Z : No. of bitstreams: 1 2-s2.0-0021994667.pdf: 191515 bytes, checksum: bd4afc4d6c9f451ebac1cc2286882de9 (MD5) Made available in DSpace on 2014-05-26T23:55:09Z (GMT). No. of bitstreams: 0 Previous issue date: 1985-01-01

Health-status of elderly patients with hepatocellular carcinoma (HCC) may limit surgical approach; other options are thus auspicable.The authors reviewed 98 selected patients, aged 65 to 90 years, with 149 HCC treated between 2002 and 2011. According to the extent of malignancy, health status and treatment, patients were divided into 3 groups. Sixty-one, submitted to major and minor curative resections, were in group A and B while group C included 37 patients, unsuitable for high-risk procedures and percutaneous ablation, submitted to intraoperative-radiofrequency ablation (IRFA) alone or combined with minor resections. Assessment of safety and therapeutic efficacy of this managment was evaluated.A postoperative mortality rate of 1,02% and an overall survival rate at 5 years of 62.3% were observed. Indeeed matched post-operative morbidity and mortality rates of A, B, C groups were 45%, 8%, 16.21% (p0.004) and 9 %, 0%, 0% (p= 0.112 ) respectively. 3 years overall-survival was not statistically different (p= 0.585). However 5 years survival rate and disease-free-survival rate were significantly higher in patients of group A and B (p= 0.003; p0.001).Treatment strategies to minimize treatment-related morbidity and mortality have resulted satisfactory for early and late outcomes of an heterogeneous group of elderly patients with HCC.

Pyoderma gangrenosum is a rare neutrophilic dermatosis, often associated with underlying systemic diseases. Treatment usually consists of topics and sometimes systemic immunosuppression. We present the case of a 32-year-old female patient undergoing radiation therapy for extensive recalcitrant pyoderma gangrenosum in which immunosuppressive measures were ineffective to control the disease. Treatment outcome was favourable with only mild side effects in the irradiated areas. Localized radiation therapy hence is a potential effective palliation for refractory cases of pyoderma gangrenosum, or patients unfit to undergo aggressive systemic immunosuppression.

Background The potential link between educational level and chronic liver diseases (CLD) were explored using the mortality records of liver cirrhosis, which lack accuracy and are unable to identify the different etiological factors of liver cirrhosis. Information on the association of low educational level with the severity of CLD is lacking. Aim To evaluate the potential association linking education level to etiology and clinical stage of CLD cases. Methods Consecutive enrolment of 11,107 subjects with CLD aged≥18 years prospectively recruited in two national surveys in 2001 and 2014 at one of the participating Italian liver units throughout the country. Subjects were pooled in two groups: low education level (less than high school) and high education level (completed high school or beyond). The association of demographic, etiological, and clinical stage of subjects with educational level was assessed using logistic regression analysis. In the analysis low educational level was the outcome variable. Results A total of 11,107 subjects born in Italy (mean age 55.5 years, sex ratio 1.5) were evaluated. Multiple logistic regression analysis shows that chronic HCV infection (O.R.1,38:95%,C.I.1.23-1.55), risky alcohol intake (O.R.1.96;95%,C.I.1.73-2.21) and liver cirrhosis (O.R.1.65;95%,C.I.1.46-1.85) all resulted independently associated with less than a completed high school education. HBV infection resulted independently associated with high education level (O.R.0.74;95%,C.I.0.64-0.86), reflecting changes in HBV modes of transmission in recent decades. No association was found with CLD related to non-alcoholic fatty liver disease (O.R.1.03;95%, C.I.0.81-1.30). Conclusions These findings show an independent association linking education level with viruses and alcohol-related CLD. Low educational level is associated with the severity of CLD.

Background: The epidemiology of hepatocellular carcinoma (HCC) is characterized by a dynamical temporal trend of well-established and emerging risk factors. Methods: We evaluated the temporal trend of aetiological factors of HCC over the last two decades in Italy. HCC cases were recruited from two previously published national studies in 1996 and in 2008 and HCC cases were also enlisted from two national surveys in 2001 and in 2014 enrolling consecutive subjects with chronic liver disease (CLD) referring to more than 80 liver units scattered all over the country for a 6-monthperiod. Results: Out of the 9997 subjects with CLD recruited in 2001 and the 2408 recruited in 2014, 3.3% and 5.7% (P < 0.001), respectively, had HCC. The temporal trend of HBsAg −/HCV + HCC cases significantly linearly decreased from 71.1% in 1996 to 57.2% in 2014 (P < 0.001). Conversely, that of virus-negative cases significantly linearly increased from 12.1% to 28.3% (P < 0.001). The proportion of HBV-related HCC cases showed a steady low rate, reflecting the reduced endemicity of the infection in Italy. The proportion of HCC with compensated cirrhosis (i.e., Child–Pugh A) linearly increased over time from 55.6% in 1996 to 76.0% in 2014 (P < 0.001) reflecting the growing effectiveness of semi-annual ultrasound surveillance for early detection of HCC. Conclusion: In conclusion, with decreasing viral aetiology, an overall decrease in the incidence of HCC might be expected in the future. The proportion of metabolic diseases is conversely increasing being considered as an aetiology. The growing prevalence of metabolic disorders in the general population may further increase this trend in the years to come.

Undifferentiated Nasopharyngeal Carcinoma (UNPC) is associated with Epstein-Barr Virus (EBV) and characterized by an abundant immune infiltrate potentially influencing the prognosis. Thus, we retrospectively assessed the significance of immunosuppression in the UNPC microenvironment as prognostic biomarker of treatment failure in a non-endemic area, and monitored the variation of systemic EBV-specific immunity before and after chemoradiotherapy (CRT). DNA and RNA were extracted from diagnostic biopsies obtained by tumor and adjacent mucosa from 63 consecutive EBV+ UNPC patients who underwent radical CRT. Among these patients 11 relapsed within 2 years. The expression of the EBV-derived UNPC-specific BARF1 gene and several immune-related genes was monitored through quantitative RT-PCR and methylation-specific PCR analyses. Peripheral T cell responses against EBV and BARF1 were measured in 14 patients (7 relapses) through IFN-γ ELISPOT assay. We found significantly higher expression levels of BARF1, CD8, IFN-γ, IDO, PD-L1, and PD-1 in UNPC samples compared to healthy tissues. CD8 expression was significantly reduced in both tumor and healthy tissues in UNPC patients who relapsed within two years. We observed a hypomethylated FOXP3 intron 1 exclusively in relapsed UNPC patients. Finally, we noticed a significant decrease in EBV- and BARF1-specific T-cells after CRT only in relapsing patients. Our data suggest that a high level of immunosuppression (low CD8, hypomethylated FoxP3) in UNPC microenvironment may predict treatment failure and may allow an early identification of patients who could benefit from the addition of immune modulating strategies to improve first line CRT.

In Italy, HDV infection endemicity has greatly decreased overtime. Migratory flow may change this scenario as migrants often come from high HDV endemicity areas. Here, we studied characteristics of HDV infection in Italy, particularly addressed to the birth area of subjects. Chronic HBsAg carriers consecutively referring to 9 units in Italy prospectively enrolled for a six-month period in 2019 were tested for anti-HDV by ELISA. Multiple logistic regression analysis was performed to identify anti-HDV positivity independent predictors. A total of 894 HBsAg-positive subjects were enrolled. Of them, 786 (87.9%) were tested for anti-HDV. Anti-HDV overall prevalence was 9.9% (6.4% in Italian natives and 26.4% in non-natives; P&nbsp

Purpose Delayed cord clamping for at least 60 s is recommended to improve neonatal outcomes. The aim of this study is to evaluate whether there are differences in cord BGA between samples collected after double clamping the cord or without clamping the cord, when blood collection occurs within 60 s from birth in both groups. Methods A cross-sectional study was carried out, collecting data from 6884 high-risk women who were divided into two groups based on the method of cord sampling (clamped vs unclamped). Results There were significant decrease in pH and BE values into unclamped group compared with the clamped group. This difference remained significant when considering pathological blood gas analysis parameters, with a higher percentage of pathological pH or BE values in the unclamped group. Conclusion Samples from the unclamped cord alter the acid–base parameters compared to collection from the clamped cord; however, this difference does not appear to be of clinical relevance. Findings could be due to the large sample size, which allowed to achieve a high power and to investigate very small numerical changes between groups, leading to a statistically significant difference in pH and BE between samples even when we could not appreciate any clinical relevant difference of pH or BE between groups. When blood gas analysis is indicated, the priority should be given to the timing of blood collection to allow reliable results, to assess newborns status at birth and intervene when needed.

Introduction. To evaluate the characteristics of alcohol-related chronic liver disease (CLD) in Italy and their potential changes over time. Patients and Methods. Subjects with CLD were enrolled in two national surveys performed in 2001 and in 2014 in Italy. The two surveys prospectively recruited patients aged ≥ 18 years referring to more than 80 Italian liver units scattered all over the country using similar clinical approach, analytical methods, and threshold of risky alcohol intake definition (≥ 3 units/day in men and ≥ 2 units/day in women). Results. Out of 12,256 enrolled subjects, 2,717 (22.2%) reported a risky alcohol intake. Of them, anti-HCV positive was observed in 48.3% of subjects. The overall sex ratio (M/F) was 3.1, decreasing from 3.8 in 2001 to 1.3 in 2014. Women were significantly older than men (58.9 versus 53.1 years; p<0.01) and an increasing ageing over time was observed in both sexes. The proportion of subjects with liver cirrhosis increased over time in both sexes, and decompensated stage (Child B or C) was detected in 55.9% of cases in 2001 and 46.0% in 2014. Conclusions. Risky alcohol intake plays a role in more than one-fifth of CLD in Italy, with a shift over time towards an older age and a more severe liver disease stage. These data put alcohol back in the spotlight with an important role in CLD in the years to come in Italy.

Background: The information on the geographical characteristics of chronic liver diseases (CLD) in Italy is out-dated. Aim: To provide up-dated information on the geographical pattern of patients with CLD born in Italy. Methods: Patients with CLD were enrolled in two national surveys performed in 2001 and 2014, which prospectively recruited subjects aged ≥18 years referring to Italian liver units located throughout the country that apply a similar clinical approach and analytical methods. Results: The total number of patients enrolled was 11,676. Alcohol-related CLD was more frequently observed in northern/central areas (25.0% vs. 20.7%, p < .001), while HBV-related (15.4% vs. 13.3%, p = .02) and HCV-related (71.2% vs. 67.1%, p < .001) CLD prevailed in southern areas/main islands (Sicily and Sardinia). These differences were stable over time. Liver cirrhosis without HCC was diagnosed more frequently in southern area/islands than in northern/central areas (23.7% vs. 18.8%, p < .01). Moreover, an increased proportion over time of patients with cirrhosis without HCC was observed both in northern/central areas (17.3% vs. 27.4%, p < .01) and in southern area/islands (22.6% vs. 27.9%, p < .01). Conclusions: These up-dated findings show different geographical patterns of CLD in Italy, reflecting different behavioural habits and socio-economic conditions across the country. They may be useful to apply more adequate preventive measures and to allocate economic resources.

Background and purpose We conducted a prospective phase II multicentric trial to determine if radical radiation therapy to all metastatic sites might improve the progression-free survival (PFS) in oligometastatic breast cancer patients. Secondary endpoints were local control (LC), overall survival (OS) and toxicity. Methods and materials Inclusion criteria were the following: oligometastatic breast cancer with ≤5 metastatic sites, FDG-PET/CT staging, no brain metastases, primary tumor controlled. Radiotherapy could be delivered using stereotactic body radiotherapy (SBRT) technique or fractionated intensity modulated radiotherapy (IMRT). SBRT consisted of 30–45 Gy in 3 fractions, while IMRT was delivered to a total dose of 60 Gy in 25 fractions. We hypothesized that radical radiation therapy could increase the PFS from 30% (according to the published literature) to 50% at two years. Results 54 Patients with 92 metastatic lesions were enrolled. Forty-four were treated with SBRT, and 10 with IMRT. Forty-eight (89%) patients received a form of systemic therapy concomitantly to radiation therapy. Sites of metastatic disease were the following: bones 60 lesions, lymph nodes 23 lesions, lung 4 lesions, liver 5 lesions. After a median follow-up of 30 months (range, 6–55 months), 1- and 2-year PFS was 75% and 53%, respectively. Two-year LC and OS were 97% and 95%, respectively. Radiation therapy was well tolerated, and no Grade ≥3 toxicity was documented. Grade 2 toxicity were pain and fatigue in 2 cases. Conclusions Patients with oligometastatic breast cancer treated with radical radiotherapy to all metastatic sites may achieve long-term progression-free survival, without significant treatment-related toxicity. While waiting for data from randomized trials, the use of radical radiation therapy to all metastatic sites in patients with oligometastatic breast cancer should be considered a valuable option, and its recommendation should be individualized.

Objective: To report the results of a national survey investigating the pattern of practiceof curative re-irradiation (ReRT) for recurrent squamous cell carcinoma of the head andneck. Methods: In March 2016, a 22-item, 4-section questionnaire was sent to all Italian Radiation Oncology centers. Sections were focused on assessing the expertise level of each center and collecting specific information on reRT prescription modalities in the adjuvant and definitive settings. Results: Overall, 77 centers completed the survey. The majority (50/77, 64.9%) of participating radiation oncologists were senior consultants (> 10 years of experience). Of the responding centers, 63 (81.8%) performed curative ReRT, while 14 (18.1%) did not, mainly (5/14, 35.7%) due to the avoidance of severe toxicity. The use of adjuvant ReRT was reported by less than half of the interviewed radiation oncologists (36/77, 46.7%). In case of unresectable local recurrence, definitive ReRT was claimed to be adopted in 55/77 (71.4%) for non-nasopharyngeal and 47/77 (61%) for nasopharyngeal cancer. The preferred treatment technique was Intensity Modulated Radiation Therapy (IMRT) followed by Stereotactic Body Radiation Therapy (SBRT). When IMRT was applied, the most common (19/55 responders, 34.5%) selection of treatment volume consisted of the Gross Tumor Volume (GTV) + 0.5 cm margin to account for microscopic disease. Conclusion: Despite the absence of definitive evidence-based recommendations, apossible consideration for ReRT in case of unresectable recurrent head and neckcancer was reported by over 80% of radiation oncologists taking part in the nationalsurvey

Background: There is increasing awareness of HBV reactivation in HCV-RNA-positive/HBV-coinfected patients with chronic liver disease (CLD) treated with oral direct-acting antivirals (DAAs). Aim: To provide figures on the prevalence of HBV markers in HCV-RNA-positive subjects in Italy, where these findings are lacking. Methods: All subjects aged ≥18 years with CLD consecutively referring to Italian liver units located throughout country were prospectively enrolled in two national surveys in 2001 and 2014. Results: The total number of HCV-RNA-positive cases was 6984; 356 (5.1%) subjects vaccinated against HBV were excluded. A total of 6628 cases were evaluated. The prevalence rates of HBsAg, isolated anti-HBc and anti-HBc/anti-HBs-positivity were 2.9%, 8.1% and 14.7%, respectively. Among the estimated one million HCV-RNA-positive subjects in Italy, a substantial number of subjects are at risk of HBV reactivation due to DAA therapy. The prevalence of liver cirrhosis was higher than that of CLD in HBsAg-positive subjects (4.4% vs. 2.6%, p < 0.01) but not in those positive for other HBV markers. Conclusions: These findings outline the burden of HBV markers among HCV-RNA-positive subjects in Italy, where in 2017 reimbursement for DAA therapy by the National Health System became universal for all patients with chronic HCV infection. HBV vaccination coverage should be greatly extended, since nearly two thirds of subjects in this study resulted negative for any HBV marker.

Background & Aims: Despite the excellent efficacy of direct-acting antivirals (DAA) reported in clinical trials, virological failures can occur, often associated with the development of resistance-associated substitutions (RASs). This study aimed to characterize the presence of clinically relevant RASs to all classes in real-life DAA failures. Methods: Of the 200 virological failures that were analyzed in 197 DAA-treated patients, 89 with pegylated-interferon+ribavirin (PegIFN+RBV) and 111 without (HCV-1a/1b/1g/2/3/4=58/83/1/6/24/25; 56.8% treatment experienced; 65.5% cirrhotic) were observed. Sanger sequencing of NS3/NS5A/NS5B was performed by home-made protocols, at failure (N= 200) and whenever possible at baseline (N= 70). Results: The majority of the virological failures were relapsers (57.0%), 22.5% breakthroughs, 20.5% non-responders. RAS prevalence varied according to IFN/RBV use, DAA class, failure type and HCV genotype/subtype. It was 73.0% in IFN group vs 49.5% in IFN free, with the highest prevalence of NS5A-RASs (96.1%), compared to NS3-RASs (75.9% with IFN, 70.5% without) and NS5B-RASs (66.6% with IFN, 20.4% without, in sofosbuvir failures). In the IFN-free group, RASs were higher in breakthrough/non-responders than in relapsers (90.5% vs 40.0%, P= 2 DAA classes showed multiclass resistance, including 11/11 NS3+NS5A failures. Furthermore, 20.0% of patients had baseline-RASs, which were always confirmed at failure. Conclusions: In our failure setting, RAS prevalence was remarkably high in all genes, with a partial exception for NS5B, whose limited resistance is still higher than previously reported. This multiclass resistance advocates for HCV resistance testing at failure, in all three genes for the best second-line therapeutic tailoring.

Background and Aim The universal hepatitis B vaccination for infants and 12-year-old adolescents (the latter limited to the first 12 years of application) was launched in Italy in 1991. Twenty-three years later we evaluated the impact of the vaccination campaign on the burden of HBsAg-positive chronic liver diseases (CLD). Material and Methods 513 HBsAg-positive chronic carriers referring to 16 Italian liver units were investigated and compared with HBsAg carriers enrolled in previous surveys. Results The proportion of inactive carriers decreased from 20.0% in 2001 to 3.3% in 2014, while that of cirrhotic patients increased from 22.6 to 33.2%. Regarding the age class 0–33 (fully covered by HBV vaccination in 2014), the rate of inactive carriers decreased from the 21.7% in 2001 to 5.9% in 2014, that of chronic hepatitis from 17.5 to 5.2% and that of cirrhosis cases from 26.4 to 4.1%. Instead, in the over-60 age group the rate of inactive carriers increased from 22.8 to 41.2% and that of chronic hepatitis from 16.8 to 46%; the rate of patients with cirrhosis ranged from 5 to 8% in different studies. Conclusion Twenty-three years after the introduction universal HBV vaccination in Italy, the clinical presentation of CLD had shown a shift towards older ages and more severe diseases. This article is protected by copyright. All rights reserved

Background: The endemicity of hepatitis delta virus infection in Italy has decreased in the last decades. Aim: To evaluate the current epidemiology of chronic delta infection in Italy and to compare the present findings with the corresponding figures from the previous studies. Methods: A cross-sectional study involving 16 referral centres scattered all over the country in 2014. Results: Out of the 513 hepatitis B surface antigen-positive subjects enrolled, 61 (11.9%) were anti-delta positive, with a sex ratio (M/F) of 2.05. The majority (80.3%) of them was 50 years or older, while the proportion of subjects younger than 30 years of age was as low as 3.3%. No difference was detected by geographical area of residence. The presence of liver cirrhosis was diagnosed in 52.4% of cases. In comparison to previous studies, a further shift towards the oldest age groups and an increasing proportion of subjects having liver cirrhosis among all anti-delta-positive subjects are observed. Conclusions: Currently, hepatitis delta infection mostly affects old people who have an advanced but indolent liver disease, reflecting a survival effect. The defective hepatitis delta virus is near to disappear in the country, where it has been discovered in the second half of 70s.