Supply chain network design for the diffusion of a new product

Supply Chain Network Design (SCND) deals with the determination of the physical configuration and infrastructures of the supply chain. Specifically, facility location is one of the most critical decisions: transportation, inventory and information sharing decisions can be readily re-optimized in response to changes in the context, while facility location is often fixed and difficult to change even in the medium term. On top of this, when designing a supply network to support a new product diffusion (NPD), the problem becomes both dynamic and stochastic. While literature concentrated on approaching SCND for NPD separately coping with dynamic and stochastic issues, we propose an integrated optimisation model, which allows warehouse positioning decisions in concert with the demand dynamics during the diffusion stage of an innovative product/service. A stochastic dynamic model, which integrates a Stochastic Bass Model (SBM) in order to better describe and capture demand dynamics, is presented. A myopic policy is elaborated in order to solve and validate on the data of a real case of SCND with 1,400 potential market points and 28 alternatives for logistics platforms

Simplifying the Virtual Safety Stock formula

The paper deepen the analysis into the Virtual Safety Stock theory, which is an approach intended to drastically reduce safety inventory levels exploiting the eventual time lag between the moment when a product is ordered and the time the product needs to be available, while preserving the same performance as a production system that operates with physical safety stock. The original virtual safety stock definition embeds two major problems: a double Gaussian integral in the formulation together with the heritage of the unrealistic assumptions already included in the earliest Hadley and Whitin’s safety stock conception. This paper describes an alternative approach in which the virtual safety stock is defined with a closed-form expression much easier to compute and use in operations management practice

Depannage and other maintenance strategies for transportation fleets

This paper addresses the problem of designing a depannage service network for freight transportation fleets in order to fill up an evident gap in Operations Management literature. As a matter of fact, breakdowns have a significant impact on service level and an efficient and effective assistance service is needed in order to guarantee competitive advantage. Aiming at laying the foundations for further research on modelling and solving the considered problem, a literature review is performed for identifying analogies with other problems, already approached in the past, and stating the problem. Finally, parameters, decision variables and objective function that should be considered for modelling and solving the problem are proposed, trying to stimulate the discussion on a new research theme and, more specifically, on the integration of decisions at strategic, tactical and operational level into a systemic model

An Operations management approach for radiology services

This paper focus on the application of Operations Management techniques in the context of radiological and diagnostic imaging services provision. More specifically, the outpatient appointment scheduling problem for MRI diagnostic imaging services in a radiology clinics is approached and solved taking into account set-up time minimization. This is pursued trough the design of an innovative system for the on-line assignment of appointments for specific diagnostic imaging scans. An appointment rule, a patient classification and an heuristic procedure for the booking process are defined in order to better manage uncertainty and improve system performance. The proposed approach was validated on the case of a diagnostic centre of Alliance Medical, a primary multinational company in the field of diagnostic imaging services

Improving management effectiveness and overall performance of software development projects through a system dynamics approach

While existing research has mainly focused on project management’s static view, our work investigates the impacts of projects’ structure and behavioural dynamics on their performance, with a specific focus on the influence of some peculiar development processes. A dynamic simulation model of a single phase project was built using the system dynamics methodology. The model integrates several previously developed and tested project structures and adds a separate structure for the negotiation process. Simulations describe the behaviours generated by the interaction of customized development processes in single-phase projects. Project performances are measured in terms of time, quality and cost. Our research aims to show that development processes, as well as shared resource levelling techniques, significantly impact the dynamic behaviour of projects through the feedback, delays and nonlinear relationships which are usually omitted in traditional project management practice, as well as in methods, tools and models, but are very important descriptors of project complexity. Expanding the models used to manage projects to include dynamic features requires a change of focus by researchers and practitioners. The system dynamics methodology provides some of the tools for developing and implementing such an expansion in project models

CA-IX-Expressing Small Extracellular Vesicles (sEVs) Are Released by Melanoma Cells under Hypoxia and in the Blood of Advanced Melanoma Patients

Cutaneous melanoma is a highly aggressive skin cancer, with poor prognosis. The tumor microenvironment is characterized by areas of hypoxia. Carbonic anhydrase IX (CA-IX) is a marker of tumor hypoxia and its expression is regulated by hypoxia-inducible factor-1 (HIF-1). CA-IX has been found to be highly expressed in invasive melanomas. In this study, we investigated the effects of hypoxia on the release of small extracellular vesicles (sEVs) in two melanoma in vitro models. We demonstrated that melanoma cells release sEVs under both normoxic and hypoxic conditions, but only hypoxia-induced sEVs express CA-IX mRNA and protein. Moreover, we optimized an ELISA assay to provide evidence for CA-IX protein expression on the membranes of the sEVs. These CA-IX-positive sEVs may be exploited as potential biomarkers for liquid biopsy

Hedgehog Pathway Inhibition by Novel Small Molecules Impairs Melanoma Cell Migration and Invasion under Hypoxia

Melanoma is the principal cause of death in skin cancer due to its ability to invade and cause metastasis. Hypoxia, which characterises the tumour microenvironment (TME), plays an important role in melanoma development, as cancer cells can adapt and acquire a more aggressive phenotype. Carbonic anhydrases (CA) activity, involved in pH regulation, is related to melanoma cell migration and invasion. Furthermore, the Hedgehog (Hh) pathway, already known for its role in physiological processes, is a pivotal character in cancer cell growth and can represent a promising pharmacological target. In this study, we targeted Hh pathway components with cyclopamine, glabrescione B and C22 in order to observe their effect on carbonic anhydrase XII (CAXII) expression especially under hypoxia. We then performed a migration and invasion assay on two melanoma cell lines (SK-MEL-28 and A375) where Smoothened, the upstream protein involved in Hh regulation, and GLI1, the main transcription factor that determines Hh pathway activation, were chemically inhibited. Data suggest the existence of a relationship between CAXII, hypoxia and the Hedgehog pathway demonstrating that the chemical inhibition of the Hh pathway and CAXII reduction resulted in melanoma migration and invasion impairment especially under hypoxia. As in recent years drug resistance to small molecules has arisen, the development of new chemical compounds is crucial. The multitarget Hh inhibitor C22 proved to be effective without signs of cytotoxicity and, for this reason, it can represent a promising compound for future studies, with the aim to reach a better melanoma disease management

Altered Antioxidant-Oxidant Status in the Aqueous Humor and Peripheral Blood of Patients with Retinitis Pigmentosa

Retinitis Pigmentosa is a common form of hereditary retinal degeneration constituting the largest Mendelian genetic cause of blindness in the developed world. It has been widely suggested that oxidative stress possibly contributes to its pathogenesis. We measured the levels of total antioxidant capacity, free nitrotyrosine, thiobarbituric acid reactive substances (TBARS) formation, extracellular superoxide dismutase (SOD3) activity, protein, metabolites of the nitric oxide/cyclic GMP pathway, heme oxygenase-I and inducible nitric oxide synthase expression in aqueous humor or/and peripheral blood from fifty-six patients with retinitis pigmentosa and sixty subjects without systemic or ocular oxidative stress-related disease. Multivariate analysis of covariance revealed that retinitis pigmentosa alters ocular antioxidant defence machinery and the redox status in blood. Patients with retinitis pigmentosa present low total antioxidant capacity including reduced SOD3 activity and protein concentration in aqueous humor. Patients also show reduced SOD3 activity, increased TBARS formation and upregulation of the nitric oxide/cyclic GMP pathway in peripheral blood. Together these findings confirmed the hypothesis that patients with retinitis pigmentosa present reduced ocular antioxidant status. Moreover, these patients show changes in some oxidative-nitrosative markers in the peripheral blood. Further studies are needed to clarify the relationship between these peripheral markers and retinitis pigmentosa

Polarized Raman mapping and phase-transition by CW excitation for fast purely optical characterization of VO2 thin films

Vanadium dioxide has attracted much interest due to the drastic change of the electrical and optical properties it exhibits during the transition from the semiconductor state to the metallic state, which takes place at a critical temperature of about 68 °C. Much study has been especially devoted to developing advanced fabrication methodologies to improve the performance of VO2 thin films for phase-change applications in optical devices. Films structural and morphological characterisation is normally performed with expensive and time consuming equipment, as x-ray diffractometers, electron microscopes and atomic force microscopes. Here we propose a purely optical approach which combines Polarized Raman Mapping and Phase-Transition by Continuous Wave Optical Excitation (PTCWE) to acquire through two simple measurements structural, morphological and thermal behaviour information on polycrystalline VO2 thin films. The combination of the two techniques allows to reconstruct a complete picture of the properties of the films in a fast and effective manner, and also to unveil an interesting stepped appearance of the hysteresis cycles probably induced by the progressive stabilization of rutile metallic domains embedded in the semiconducting monoclinic matrix