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Introduction: This retrospective study on patients with biopsy-proven lupus nephritis (LN) aimed to assess the probability of sustained clinical remission (sCR) and to investigate sCR effects on disease flares and impaired kidney function (IKF). Methods: sCR was defined as clinical-Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) = 0 and estimated glomerular filtration rate (eGFR) >60 ml/min per 1.73 m2 lasting ≥1 year; IKF: eGFR <60 ml/min per 1.73 m2 for >3 months. We analyzed the probability of achieving and maintaining sCR, and the yearly risk of flare. Cox models were used to identify predictors of sCR and IKF with variables analyzed as time-dependent covariates when appropriate. Results: Of 303 patients followed-up with for 14.8 (interquartile range: 9.8–22) years, 257 (84.8%) achieved sCR. The probability of achieving sCR progressively increased over time reaching 90% at 15 years. Baseline age (hazard ratio [HR]: 1.017; 95% confidence interval [CI]: 0.005–1.029; P = 0.004), hydroxychloroquine intake (HR: 1.385; 95% CI: 1.051–1.825; P = 0.021), and absence of arterial hypertension (HR: 0.699; 95% CI: 0.532–0.921; P = 0.011) were independent predictors of sCR. Among patients who achieved sCR, 142 (55.3%) developed a lupus flare after a median time of 3.6 (2.3–5.9) years. In the remaining 115 patients, sCR persisted for 9.5 (5.8–14.5) years. The probability of sCR to persist at 15 years was 38%. SLE flare risk decreased to 10%, 5%, and 2% in patients with sCR lasting <5, 5 to 10, and >10 years, respectively. At the last observation, 57 patients (18.81%) had IKF. sCR achievement (HR: 0.18, P < 0.001) and its duration (HR: 0.83, P < 0.001) were protective against IKF. Conclusion: sCR is an achievable target in LN management and protects against IKF. The longer the sCR, the higher the chance of its persistence and the lower the risk of SLE flares.

Implementing a circular economy in cities has been proposed by policy makers as a potential solution for achieving sustainability in the construction sector. One strategy that has gained interest by both policy makers and companies is to develop “circular construction hubs”: locations that collect, store, and redistribute waste as secondary resources. However, there is limited literature taking a spatially explicit view, identifying the spatial parameters that could affect the locations of hubs both for now and in the future. This study therefore aims to categorize different types of circular hubs for the construction industry, collect spatial parameters required for finding suitable locations for each type of circular hub, and translate the spatial parameters into a list of data and spatial analysis methods that could be used to identify potential future locations. The study used the Netherlands as a case study, extracting spatial parameters from two sources: Dutch governmental policy documents on circular economy and spatial development and interviews with companies operating circular hubs. Four types of circular construction hubs were identified: urban mining hubs, industry hubs, local material banks, and craft centers. The spatial parameters were extracted for each type of hub from four perspectives: resources (such as material type, business model), accessibility (such as mode and scale of transportation), land use (such as plot size, land use), and socio-economic (such as labor availability). The parameters were then translated into a list of spatial data and analysis methods required to identify future locations of circular construction hubs., Environmental & Climate Design, Environmental Technology and Design

Transitioning towards a circular built environment and turning waste into resources have become one of the new sustainability paradigms today. However, a circular transition can be considered a ‘wicked problem’. The multiple dimensions and scales of the circular transition and its substantial spatial implications fit well into the planning approach of Geodesign. The Horizon 2020 funded project “Resource Management in the periurban Areas - Going beyond Urban Metabolism (REPAiR)” implemented an innovative Geodesign approach. Moreover, it explored its capability to support spatial decision-making processes for the circular economy transition of the built environment within urban planning practices. This article aims to understand to what extent a process of Geodesign, which is conducted with the support of a digital tool and a Living Lab approach, can support the creation of localised circular economy strategies and foster the circular economy transition in cities and territories. The analysis explores and compares the results of three European cases -Amsterdam, Hamburg and Naples. It considers the kind of data input required to run the process in every phase, the stakeholders involved and their typology, the specific urban or territorial, planning and governance scales of analysis, and the final output definition after the Geodesign process implementation. The approach outputs constitute a decision support system for easing negotiations between local actors regarding the circularity strategies to implement. The findings reveal an intertwinement between different forms of knowledge included in the process, ranging from sustainability to governance and design, and the actors engaged in planning a circularity transition spatially. However, even using similar starting data, the local information and the starting conditions strongly influence the process and the types of strategies elaborated in each case., Environmental Technology and Design, Real Estate Management

Centered at the Jožef Stefan Institute, Ljubljana, Slovenia, five top research & innovation partners across Europe are creating an innovation hub to study microbe-colloid–surface interactions using high-tech methodologies and equipment. The SURFBIO Innovation Hub aims to provide biotechnology researchers, academic institutions, industry and policy makers with training services and assessments to optimize novel materials for a variety of applications and will offer new, industry-oriented, research services opened to industry and institutions, covering all the needs in only one Hub, and collecting the activities together. This will lead to the founding of a SURFBIO professional society to act as a network center with the goal of fostering advanced microbial materials applications throughout Europe. Understanding the interactions of colloids (microorganisms, nanoparticles and biomolecules) with surfaces and between themselves is a key factor that can lead to improvements of advanced materials. As such the emerging field of Colloid Biology is positioned on the intersection between material science and molecular microbiology, dealing with artificial multispecies bio-aggregates, bio- films and bio-nano-constructs of bacteria and nanoparticles, to create novel advanced materials. The colloid-biological interactions can be studied and analyzed by applying different tools and techniques. Impacts of the networking activities will be: • high-impact research results on surface and colloid biology • improved knowledge transfer • increased patenting • increased peer-reviewed publications on the topic • expanded range of testable samples • contract research for industry • boosted interest on surface and colloid biology • standardization of methodologies • new possibilities in analytical testing So far, two public handbooks, two webinars and two MOOCs have been prepared and are available freely via the SURFBIO website (https://surfbio.eu/) providing information and training on the

Centered at the Jožef Stefan Institute, Ljubljana, Slovenia, five top research & innovation partners across Europe are creating an innovation hub to study microbe-colloid–surface interactions using high-tech methodologies and equipment. The SURFBIO Innovation Hub aims to provide biotechnology researchers, academic institutions, industry and policy makers with training services and assessments to optimize novel materials for a variety of applications and will offer new, industry-oriented, research services opened to industry and institutions, covering all the needs in only one Hub, and collecting the activities together. This will lead to the founding of a SURFBIO professional society to act as a network center with the goal of fostering advanced microbial materials applications throughout Europe. Understanding the interactions of colloids (microorganisms, nanoparticles and biomolecules) with surfaces and between themselves is a key factor that can lead to improvements of advanced materials. As such the emerging field of Colloid Biology is positioned on the intersection between material science and molecular microbiology, dealing with artificial multispecies bio-aggregates, bio- films and bio-nano-constructs of bacteria and nanoparticles, to create novel advanced materials. The colloid-biological interactions can be studied and analyzed by applying different tools and techniques. Impacts of the networking activities will be: • high-impact research results on surface and colloid biology • improved knowledge transfer • increased patenting • increased peer-reviewed publications on the topic • expanded range of testable samples • contract research for industry • boosted interest on surface and colloid biology • standardization of methodologies • new possibilities in analytical testing So far, two public handbooks, two webinars and two MOOCs have been prepared and are available freely via the SURFBIO website (https://surfbio.eu/) providing information and training on the

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.

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.

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., Environmental Technology and Design

BACKGROUND AND PURPOSE: Currently, human papillomavirus (HPV) positivity represents a strong prognostic factor for both reduced risk of relapse and improved survival in patients with oropharyngeal squamous cell carcinoma (OPSCC). However, a subset of HPV-positive OPSCC patients still experience poor outcomes. Furthermore, HPV-negative OPSCC patients, who have an even higher risk of relapse, are still lacking suitable prognostic biomarkers for clinical outcome. Here, we evaluated the prognostic value of LINE-1 methylation level in OPSCC patients and further addressed the relationship between LINE-1 methylation status and p53 protein expression as well as genome-wide/gene-specific DNA methylation. RESULTS: In this study, DNA was extracted from 163 formalin-fixed paraffin-embedded tissue samples retrospectively collected from stage III-IVB OPSCC patients managed with curative intent with up-front treatment. Quantitative methylation-specific PCR revealed that LINE-1 hypomethylation was directly associated with poor prognosis (5-year overall survival-OS: 28.1% for LINE-1 methylation < 35% vs. 69.1% for ≥ 55%; p < 0.0001). When LINE-1 methylation was dichotomized as < 55% versus ≥ 55%, interaction with HPV16 emerged: compared with hypermethylated HPV16-positive patients, subjects with hypomethylated HPV16-negative OPSCC reported an adjusted higher risk of death (HR 4.83, 95% CI 2.24-10.38) and progression (HR 4.54, 95% CI 2.18-9.48). Tumor protein p53 (TP53) gene is often mutated and overexpressed in HPV-negative OPSCC. Since p53 has been reported to repress LINE-1 promoter, we then analyzed the association between p53 protein expression and LINE-1 methylation levels. Following p53 immunohistochemistry, results indicated that among HPV16-negative patients with p53 ≥ 50%, LINE-1 methylation levels declined and remained stable at approximately 43%; any HPV16-positive patient reported p53 ≥ 50%. Finally, DNA methylation analysis demonstrated that genome-wide average methylat

Any process of growth, decline and transformation can be understood from a spatial reading, unraveling the traces left on the ground and observing elements temporarily unable to adapt to the flow of time: wasteland. The concept of wasteland is an artificial ‘construction’ usually linked to the idea of (un)productivity. As society changes, the productive use of land changes through time. This chapter aims to reveal the cumulative alternation of western perception in land use value. The means to read this shift is the historical cartographic analysis on the Southside of Antwerp (Belgium). As constructions of reality, maps are loaded with intentions and interpretations of the culture in which they are produced. In particular, the historical mapping of wastelands generated by industrial and agricultural production focuses on understanding the evolution in interpreting fundamental issues such as time, processes and changes related to land ownership., Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care. Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public., Environmental Technology and Design

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., Environmental Technology and Design

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

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 value chains 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 the potential 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., Environmental Technology and Design, Climate Design and Sustainability

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 value chains 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 the potential 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., Environmental Technology and Design, Climate Design and Sustainability

Contains fulltext : 202828.pdf (publisher's version ) (Open Access)

The concept of circular economy (CE) is high on the agenda of many planning agencies in European countries. It has also become a prominent issue in European academic education institutions. It is expected that spatial planning and design can support and add the spatial quality dimension of such a transition towards CE. However, incorporating the concept of CE in an integrative manner in urban design and planning courses is challenging because of its metabolic and complex nature. This article presents the first results of integrating design-teaching activities at a faculty of architecture with an H2020-financed research project. The integration of research and design education provided the students with a situated and indeed transdisciplinary learning environment. Students understood that they needed to address challenges from a systemic perspective rather early in the design process, meaning to understand what the relations between different subsystems and their spatial structures are. Furthermore, the experiment provided evidence that the eco-innovative solutions developed by the students are seen as an effective option to achieve objectives for a transition towards CE by stakeholders., Environmental Technology and Design, Spatial Planning and Strategy

‘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, Environmental Technology and Design

Contains fulltext : 202828.pdf (publisher's version ) (Open Access)

Contains fulltext : 202828.pdf (publisher's version ) (Open Access)

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 <7 at 5 minutes (P < 0.002). In the NB Group none of the 6 newborns who had a pathological BGA had an adverse outcome. While, within the CB Group, all the 12 newborns who had an adverse outcome, were identify among the 28 neonates with a pathological BGA. Discussion: An appropriate midwifery care should allow to select the CB group within the low risk population, and to perform the BGA when recommended.

The concept of circular economy (CE) is high on the agenda of many planning agencies in European countries. It has also become a prominent issue in European academic education institutions. It is expected that spatial planning and design can support and add the spatial quality dimension of such a transition towards CE. However, incorporating the concept of CE in an integrative manner in urban design and planning courses is challenging because of its metabolic and complex nature. This article presents the first results of integrating design-teaching activities at a faculty of architecture with an H2020-financed research project. The integration of research and design education provided the students with a situated and indeed transdisciplinary learning environment. Students understood that they needed to address challenges from a systemic perspective rather early in the design process, meaning to understand what the relations between different subsystems and their spatial structures are. Furthermore, the experiment provided evidence that the eco-innovative solutions developed by the students are seen as an effective option to achieve objectives for a transition towards CE by stakeholders., Environmental Technology and Design, Spatial Planning and Strategy

‘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, Environmental Technology and Design

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

AIM: To check the safety and efficacy of boceprevir/ telaprevir with peginterferon/ribavirin for hepatitis C virus (HCV) genotype 1 in the real-world settings. METHODS: This study was a non-randomized, observational, prospective, multicenter. This study involved 47 centers in Italy. A database was prepared for the homogenous collection of the data, was used by all of the centers for data collection, and was updated continuously. All of the patients enrolled in this study were older than 18 years of age and were diagnosed with chronic infection due to HCV genotype 1. The HCV RNA testing was performed using COBAS-TaqMan2.0 (Roche, LLQ 25 IU/mL). RESULTS: All consecutively treated patients were included. Forty-seven centers enrolled 834 patients as follows: Male 64%; median age 57 (range 18-78), of whom 18.3% were over 65; mean body mass index 25.6 (range 16-39); genotype 1b (79.4%); diagnosis of cirrhosis (38.2%); and fibrosis F3/4 (71.2%). The following drugs were used: Telaprevir (66.2%) and PEG-IFN-alpha2a (67.6%). Patients were naïve (24.4%), relapsers (30.5%), partial responders (14.8%) and null responders (30.3%). Overall, adverse events (AEs) occurred in 617 patients (73.9%) during the treatment. Anemia was the most frequent AE (52.9% of cases), especially in cirrhotic. The therapy was stopped for 14.6% of the patients because of adverse events or virological failure (15%). Sustained virological response was achieved in 62.7% of the cases, but was 43.8% in cirrhotic patients over 65 years of age. CONCLUSION: In everyday practice, triple therapy is safe but has moderate efficacy, especially for patients over 65 years of age, with advanced fibrosis, nonresponders to peginterferon + ribavirin.

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: 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.

Contains fulltext : 193578.pdf (publisher's version ) (Open Access)

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, Version 2. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No 688920., Climate Design and Sustainability, Environmental Technology and Design

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., Environmental Technology and Design

Contains fulltext : 193578.pdf (publisher's version ) (Open Access)

Contains fulltext : 193578.pdf (publisher's version ) (Open Access)

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., Environmental Technology and Design

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, Version 2. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No 688920., Climate Design and Sustainability, Environmental Technology and Design

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 30-45Gy in 3 fractions, while IMRT was delivered to a total dose of 60Gy 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 30months (range, 6-55months), 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.

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 <5 cm and an interval from primary radiation ≥6 months, were the prevalent predictive factors considered for reRT. Sixty percent of reirradiated patients had already received a salvage therapy, either chemotherapy (40%) or reoperation (20%). The most common approach for reRT was fractionated stereotactic radiotherapy to a mean (photon) dose of 41.6 Gy. 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

The big data approach offers a powerful alternative to Evidence-based medicine. This approach could guide cancer management thanks to machine learning application to large-scale data. Aim of the Thyroid CoBRA (Consortium for Brachytherapy Data Analysis) project is to develop a standardized web data collection system, focused on thyroid cancer. The Metabolic Radiotherapy Working Group of Italian Association of Radiation Oncology (AIRO) endorsed the implementation of a consortium directed to thyroid cancer management and data collection. The agreement conditions, the ontology of the collected data and the related software services were defined by a multicentre ad hoc working-group (WG). Six Italian cancer centres were firstly started the project, defined and signed the Thyroid COBRA consortium agreement. Three data set tiers were identified: Registry, Procedures and Research. The COBRA-Storage System (C-SS) appeared to be not time-consuming and to be privacy respecting, as data can be extracted directly from the single centre's storage platforms through a secured connection that ensures reliable encryption of sensible data. Automatic data archiving could be directly performed from Image Hospital Storage System or the Radiotherapy Treatment Planning Systems. The C-SS architecture will allow “Cloud storage way” or “distributed learning” approaches for predictive model definition and further clinical decision support tools development. The development of the Thyroid COBRA data Storage System C-SS through a multicentre consortium approach appeared to be a feasible tool in the setup of complex and privacy saving data sharing system oriented to the management of thyroid cancer and in the near future every cancer type.

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

BACKGROUND: Inclusion of new biomarkers to improve a personalized treatment approach for oropharyngeal squamous cell carcinoma (OPSCC) is urgently needed. Hypomethylation of the Long interspersed nucleotide element-1 (LINE-1) repetitive elements, a widely accepted surrogate of overall genomic DNA methylation content, was found to be associated with a poor prognosis in several cancers. At present, no studies have investigated the influence of LINE-1 methylation levels on OPSCC relapse. The main goal of this study was the evaluation of the prognostic value of LINE-1 methylation status in predicting early tumor relapse in locally advanced OPSCC. METHODS: We retrospectively reviewed a cohort of 77 patients with stage III-IVB OPSCC. Methylation of LINE-1 repetitive sequences was evaluated by real-time quantitative methylation-specific PCR in formalin-fixed paraffin-embedded tissues. The prognostic relevance of LINE-1 methylation was assessed by comparing patients who relapsed within 2 years from the end of treatment (cases) with those who did not (controls). Results were validated in an independent cohort of 33 patients with OPSCC. RESULTS: With respect to early OPSCC relapse, the mean LINE-1 methylation level was significantly lower in relapsed cases than in control group (p < 0.01). Interestingly, LINE-1 methylation was lower in relapsed cases than in controls in both HPV16-negative and HPV16-positive OPSCC patients, even if statistical significance was reached only for the former group (p = 0.01). LINE-1 methylation levels were also significantly reduced in relapsed cases with respect to the controls in OPSCC current smokers (p = 0.02). Consistently, in HPV16-negative current smokers, OPSCC relapse was significantly associated with decreased levels of LINE-1 methylation (p = 0.02). Using logistic regression model, we found that patients with hypomethylated LINE-1 were associated with a 3.5 higher risk of early relapse than hypermethylated ones (OR = 3.51; 95% CI 1.03

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

Objectives:The occurrence of decompensation marks a crucial turning point i. The course of cirrhosis. The purpose of this study was to asses. The risk of mortality according t. The clinical characteristics of first decompensation, considering als. The impact of acute-on-chronic liver failure (AoCLF).Methods:We conducted a prospective nationwide inception cohort study in Italy. Decompensation was defined b. The presence of ascites, either overt or detected by ultrasonography (UD), gastroesophageal variceal bleeding (GEVB), and hepatic encephalopathy (HE). AoCLF was defined according t. The Asian Pacific Association fo. The Study o. The Liver criteria. Multivariable Cox proportional hazards regression was used to analyz. The risk of failure (death or orthotopic liver transplantation (OLT)).Results:A total of 490 consecutive cirrhotic patients (314 males, mean age 60.9±12.6 years) fulfille. The study criteria. AoCLF was identified in 59 patients (12.0%). Amon. The remaining 431 patients, ascites were found in 330 patients (76.6%): in 257 (77.8%) as overt ascites and in 73 (22.2%) as UD ascites. GEVB was observed in 77 patients (17.9%) and HE in 30 patients (7.0%). After a median follow-up of 33 months, 24 patients underwent OLT and 125 died. The cumulative incidence of failure (death or OLT) after 1, 2, and 3 years was, respectively, 28, 53, and 62% in patients with AoCLF; 10, 18, and 25% in patients with UD ascites; 17, 31, and 41% in patients with overt ascites; and 8, 12, and 24% in patients with GEVB (P<0.0001).Conclusions:AoCLF is responsible for a relevant proportion of first decompensation in cirrhotic patients and is associated wit. The poorest outcome. Patients with UD ascites do not have a negligible mortality rate and require clinical monitoring similar to that of patients with overt ascites.

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.

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1554613%5DMICH-V-1554613, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1554613/MICH-V-1554613/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1554613%5DMICH-V-1554613, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1554613/MICH-V-1554613/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1554613%5DMICH-V-1554613, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1554613/MICH-V-1554613/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy