Economic sustainability under supply chain and eco-industrial park concurrent design

From a systemic point of view, the environmental efforts of single companies to achieve sustainable economic and environmental development are not enough because of the economic difficulty of reaching both zero-waste production state and high level of resource efficiency. This work focuses on payback period as a commitment keeping mechanism to ensure network stability at least until the recovery of the investment made for value creation from waste. A scenario analysis is proposed to investigate how the characteristics of each stakeholder within a network can affect the economic sustainability of the others

Economic sustainability under supply chain and eco-industrial park concurrent design

Abstract From a systemic point of view, the environmental efforts of single companies to achieve sustainable economic and environmental development are not enough because of the economic difficulty of reaching both zero-waste production state and high level of resource efficiency. This work focuses on payback period as a commitment keeping mechanism to ensure network stability at least until the recovery of the investment made for value creation from waste. A scenario analysis is proposed to investigate how the characteristics of each stakeholder within a network can affect the economic sustainability of the others

Change-point visualization and variation analysis in a simple production line: a process mining application in manufacturing

In production systems, digital twins must be always aligned with the real system to guarantee an effective decision making process in a continuously changing environment. To allow the alignment, digital models can be updated with process mining techniques through data collected by sensors. This paper addresses the issue of detecting changes in the production system by analyzing data collected from sensors. Using raw collected data, a procedure is proposed to compute and plot relevant system measures that could help change identification. Simulation is used to test the effectiveness of the procedure in a realistic medium size production line

A Discrete Event Simulation Based Approach for Digital Twin Implementation

Nowadays, manufacturing companies need to improve their production monitoring and prediction to be more flexible and re-configurable. To do so, the digitization of the manufacturing environment is a very critical issue. This paper proposes an approach to develop digital twins in this environment. Digital twins are virtual systems, real time connected with their physical counterpart, which replicate exactly their behaviour. Discrete event simulation models, connected in real-time with their real system counterparts, are developed in this work. Two industrial use cases are analysed, to show the benefits that this promising technology can bring to the manufacturing industry

Efficient Circulation of Railway Rolling Stock

Railway rolling stock (locomotives, carriages, and train units) is one of the most significant cost sources for operatorsof passenger trains, both public and private. Rolling stock costsare due to material acquisition, power supply, and material maintenance. The efficient circulation of rolling stock material is therefore one of the objectives pursued. In this paper we focus on the circulation of train units on a single line. In order to utilize the train units on this line in an efficient way, they are added to or removed from the trains in certain stations, according to the passengers

Functional reconstitution of HBV-specific CD8 T cells by in vitro polyphenol treatment in chronic hepatitis B.

Background & aims In chronic HBV infection, mitochondrial functions and proteostasis are dysregulated in exhausted HBV-specific CD8 T cells. To better characterise the potential involvement of deregulated protein degradation mechanisms in T cell exhaustion, we analysed lysosome-mediated autophagy in HBV-specific CD8 T cells. Bioactive compounds able to simultaneously target both mitochondrial functions and proteostasis were tested to identify optimal combination strategies to reconstitute efficient antiviral CD8 T cell responses in patients with chronic HBV infection. Methods Lysosome-mediated degradation pathways were analysed by flow cytometry in virus-specific CD8 T cells from patients with chronic HBV infection. Mitochondrial function, intracellular proteostasis, and cytokine production were evaluated in HBV-peptide-stimulated T cell cultures, in the presence or absence of the polyphenols resveratrol (RSV) and oleuropein (OLE) and their metabolites, either alone or in combination with other bioactive compounds. Results HBV-specific CD8 T cells from patients with CHB showed impaired autophagic flux. RSV and OLE elicited a significant improvement in mitochondrial, proteostasis and antiviral functions in CD8 T cells. Cytokine production was also enhanced by synthetic metabolites, which correspond to those generated by RSV and OLE metabolism in vivo, suggesting that these polyphenols may also display an effect after transformation in vivo. Moreover, polyphenolic compounds improved the T cell revitalising effect of mitochondria-targeted antioxidants and of programmed cell death protein 1/programmed cell death ligand 1 blockade. Conclusions Simultaneously targeting multiple altered intracellular pathways with the combination of mitochondria-targeted antioxidants and natural polyphenols may represent a promising immune reconstitution strategy for the treatment of chronic HBV infection. Lay summary In chronic hepatitis B, antiviral T lymphocytes are deeply impaired, with many altered intracellular functions. In vitro exposure to polyphenols, such as resveratrol and oleuropein, can correct some of the deregulated intracellular pathways and improve antiviral T cell function. This effect can be further strengthened by the association of polyphenols with antioxidant compounds in a significant proportion of patients. Thus, the combination of antioxidants and natural polyphenols represents a promising strategy for chronic hepatitis B therapy

Pre-treatment risk factors to predict early cisplatin-related nephrotoxicity in locally advanced head and neck cancer patients treated with chemoradiation: A single Institution experience

Objectives: Cisplatin is essential in the curative treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC) patients. The assessment of risk factors to predict an early cisplatin-induced nephrotoxicity could help in better managing one of the most relevant cisplatin-related dose-limiting factors. Material and methods: We retrospectively collected data of LA-HNSCC patients treated at our Institution from 2008 to 2019. Patients received cisplatin in a curative setting concurrently with radiation. Acute Kidney Injury (AKI) was assessed as a dichotomous variable (CreaIncr) based on pre-treatment values, and values recorded at days 6-20 post-first cycle of cisplatin. Univariable logistic regression models were performed to investigate associations between CreaIncr and clinical characteristics. A multivariable logistic model on a priori selected putative covariates was performed. Results: Of the 350 LA-HNSCC treated patients, 204 were analyzed. Ninety (44 %) suffered from any grade AKI (grade I 51.1 %): out of them, 84.4 % received high-dose cisplatin (100 mg/m2 q21). On the univariable logistic regression model, male sex, age, serum uric acid, creatinine, concomitant drugs, and cisplatin schedule were significantly associated with a higher rate of AKI. At multivariable model, age (p = 0.034), baseline creatinine (p = 0.027), concomitant drugs (p = 0.043), and cisplatin schedule (one-day bolus or fractionated high-dose vs. weekly; p = 0.001) maintained their significant association. Conclusions: Identifying pre-treatment risk factors in LA-HNSCC patients may improve decision-making in a setting where cisplatin has a curative significance. A strict monitoring of AKI could avoid cisplatin dose adjustments, interruptions, and treatment delays, thus limiting a negative impact on outcomes

HER2 status in recurrent/metastatic androgen receptor overexpressing salivary gland carcinoma patients

BackgroundOverexpression of human epidermal growth factor receptor type 2 (HER2) occurs in almost 25-30% of androgen receptor (AR)-positive salivary gland carcinomas (SGCs), notably salivary duct carcinoma (SDC) and adenocarcinoma not otherwise specified (NOS). In the last years, several studies have reported the clinical benefit of HER2 directed therapies in this setting. This work aims at describing the natural history of AR-positive recurrent/metastatic (R/M) SGC patients, based on HER2 amplification status.MethodsConsecutive R/M AR-positive SGC patients accessing our Institution from 2010 to 2021 were analyzed. Descriptive statistics and survival analyses were performed to present the clinical characteristics of the selected patients and the outcomes, based on HER2 status. A specific focus was dedicated to patients developing metastases to the central nervous system (CNS).ResultsSeventy-four R/M AR-positive SGC patients (72 men) were analyzed. Median follow-up was 36.18 months (95% CI 30.19-42.66). HER2 status was available in 62 cases (84%) and in 42% the protein was overexpressed (HER2+). Compared with patients with HER2- SGCs, in patients with HER2+ disease, HR for disease recurrence was 2.97 (95% CI 1.44-6.1, p=0.003), and HR for death from R/M disease was 3.22 (95% CI 1.39-7.49, p=0.007). Moreover, the HER2+ group showed a non-significant trend towards a higher prevalence of CNS metastases (40% vs. 24%, p=0.263). Patients developing CNS metastases had shorter survival than those who did not; at bivariate analysis (covariates: CNS disease and HER2 status), HER2 status demonstrated its independent prognostic significance.DiscussionIn our patient population, HER2 amplification was a negative prognostic factor, and it was associated with a non-statistically significant higher risk of developing CNS metastasis. Further studies are needed to explore the potential clinical benefit of tackling the two biological pathways (AR and HER2) in patients affected by this rare and aggressive malignancy