A dynamic route choice model for public transport networks with boarding queues

The concepts of optimal strategy and hyperpath were born within the framework of static frequency-based public transport assignment, where it is assumed that travel times and frequencies do not change over time and no overcrowding occurs. However, the formation of queues at public transport stops can prevent passengers from boarding the first vehicle approaching and can thus lead to additional delays in their trip. Assuming that passengers know from previous experience that for certain stops/lines they will have to wait for the arrival of the 2nd, 3rd, …, k-th vehicle, they may alter their route choices, thus resulting in a different assignment of flows across the network. The aim of this paper is to investigate route choice behaviour changes as a result of the formation and dispersion of queues at stops within the framework of optimal travel strategies. A new model is developed, based on modifications of existing algorithms

HCC development is associated to peripheral insulin resistance in a mouse model of NASH

NAFLD is the most common liver disease worldwide but it is the potential evolution to NASH and eventually to hepatocellular carcinoma (HCC), even in the absence of cirrhosis, that makes NAFLD of such clinical importance. Aim: we aimed to create a mouse model reproducing the pathological spectrum of NAFLD and to investigate the role of possible co-factors in promoting HCC. Methods: mice were treated with a choline-deficient L-amino-acid-defined-diet (CDAA) or its control (CSAA diet) and subjected to a low-dose i.p. injection of CCl 4 or vehicle. Insulin resistance was measured by the euglycemic-hyperinsulinemic clamp method. Steatosis, fibrosis and HCC were evaluated by histological and molecular analysis. Results: CDAA-treated mice showed peripheral insulin resistance at 1 month. At 1-3 months, extensive steatosis and fibrosis were observed in CDAA and CDAA+CCl4 groups. At 6 months, equal increase in steatosis and fibrosis was observed between the two groups, together with the appearance of tumor. At 9 months of treatment, the 100% of CDAA+ CCl4 treated mice revealed tumor versus 40% of CDAA mice. Insulin-like Growth Factor-2 (IGF-2) and Osteopontin (SPP-1) were increased in CDAA mice versus CSAA. Furthermore, Immunostaining for p-AKT, p-c-Myc and Glypican-3 revealed increased positivity in the tumors. Conclusions: the CDAA model promotes the development of HCC from NAFLD-NASH in the presence of insulin resistance but in the absence of cirrhosis. Since this condition is increasingly recognized in humans, our study provides a model that may help understanding mechanisms of carcinogenesis in NAFLD. © 2014 De Minicis et al

HDL cholesterol protects from liver injury in mice with intestinal specific LXRα activation

Background and aims: Liver X receptors (LXRs) exert anti-inflammatory effects even though their hepatic activation is associated with hypertriglyceridemia and hepatic steatosis. Selective induction of LXRs in the gut might provide protective signal(s) in the aberrant wound healing response that induces fibrosis during chronic liver injury, without hypertriglyceridemic and steatogenic effects. Methods: Mice with intestinal constitutive LXRα activation (iVP16-LXRα) were exposed to intraperitoneal injection of carbon tetrachloride (CCl4) for 8 weeks, and in vitro cell models were used to evaluate the beneficial effect of high-density lipoproteins (HDL). Results: After CCl4 treatment, the iVP16-LXRα phenotype showed reduced M1 macrophage infiltration, increased expression M2 macrophage markers, and lower expression of hepatic pro-inflammatory genes. This anti-inflammatory effect in the liver was also associated with decreased expression of hepatic oxidative stress genes and reduced expression of fibrosis markers. iVP16-LXRα exhibited increased reverse cholesterol transport in the gut by ABCA1 expression and consequent enhancement of the levels of circulating HDL and their receptor SRB1 in the liver. No hepatic steatosis development was observed in iVP16-LXRα. In vitro, HDL induced a shift from M1 to M2 phenotype of LPS-stimulated Kupffer cells, decreased TNFα-induced oxidative stress in hepatocytes and reduced NF-kB activity in both cells. SRB1 silencing reduced TNFα gene expression in LPS-stimulated KCs, and NOX-1 and IL-6 in HepG2. Conclusions: Intestinal activation of LXRα modulates hepatic response to injury by increasing circulating HDL levels and SRB1 expression in the liver, thus suggesting this circuit as potential actionable pathway for therapy

Municipal waste management systems for domestic use

© 2017 The Authors. Every year, the average citizen of a developed country produces about half a tonne of waste, thus waste management is an essential industry. Old waste management systems based on the collection of mixed/ sorted waste and transporting it a long way to disposal sites has a significant negative impact on the environment and humans. This paper will review the available waste management systems for house- holds. Biological methods (such as composting or anaerobic digestion) and physicochemical methods (such as burning or pyrolysis) of waste utilization will be considered from the householder’s point of view. The most important features of each system will be discussed and compared. Municipal waste management systems for domestic use could eliminate or significantly reduce the stage of waste collection and transportation. Additionally, they should not require special infrastructure and at the same time should allow garbage to be changed into safe products or energy sources with no harmful emissions. The aim of the work is to identify the best available waste disposal systems for domestic use.This reported work was conducted as part of the“Design Optimisation of the HERU Waste Treatment System”project that wasfunded by Manik Ventures Limited Project ID: 10300

Quality of dementia clinical guidelines and relevance to the care of older people with comorbidity: evidence from the literature

Gianfranco Damiani, Giulia Silvestrini, Lucrezia Trozzi, Donatella Maci, Lanfranco Iodice, Walter Ricciardi Department of Public Health, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli, Rome, Italy Purpose: The aim of this paper was to explore the applicability of dementia clinical guidelines (CGs) to older patients, to patients with one or several comorbidities, and to both targets in order to evaluate if an association between the applicability and quality of the CGs exists.Materials and methods: A systematic search strategy conducted on electronic databases identified CGs on diagnosis and treatment of dementia published from 2000 to 2013. In addition, websites of organizations devoted to the treatment and awareness of dementia were searched. The quality of evidence was assessed using the Appraisal of Guidelines Research and Evaluation (AGREE) instrument. Two investigators independently scored the relevance of the CGs by means of a specific tool. Descriptive and inferential analyses were performed (Mann–Whitney test, 0.05 α-level).Results: Twenty-two CGs met our inclusion criteria. On average, the quality of the CGs was higher than 70% in three of six domains measured by the AGREE tool. The domains with lower mean scores (less than 50%) were “Applicability” and “Editorial independence”. Considering applicability to older patients, 20 CGs (91%) addressed issues of treatment for older patients, five of them (23%) classified older patients by age, and 13 CGs (60%) addressed issues of comorbidity. Only seven (32%) discussed the quality of evidence for patients with multiple comorbid conditions. Thirteen CGs (60%) reported recommendations for patients with at least one comorbid condition, while seven of them (32%) reported on several comorbid conditions. No statistically significant association between CG quality and relevance to care of older people with or without comorbidity was found (P>0.05).Conclusion: This study showed that dementia CGs poorly address treatment for older patients with comorbidities, regardless of their quality. Therefore, they scarcely satisfy the need of modern clinical practice. Keywords: dementia, clinical guidelines, quality, older, comorbidit

A simulation environment for estimation of the performance of RSA cages.

Roentgen stereophotogrammetric analysis (RSA) is an important technique for in vivo evaluation of joint kinematics and surgical outcome. However, its accuracy is highly affected by the experimental set-up. In this paper we present a new software environment for assessing the impact of calibration cage design on the accuracy of the reconstruction of 3D points, which can be easily used for preliminary evaluations also by non-expert users. The paper presents methods of the simulator and preliminary results in a clinical standard and custom environment. The software was realized using MATLAB and developed for the PC/Windows operating system. It is freeware under request to authors