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

Unveiling the role of Carbonic Anhydrase XII in human melanoma and dendritic cells in a hypoxic microenvironment

The tumor microenvironment (TME) is characterized by low oxygen levels, a condition known as hypoxia which plays a critical role in cancer progression, immune evasion and resistance to therapy. Along with cancer cells, the TME is populated by stromal cells, which include infiltrating immune cells. The aim of the thesis was to study the relevance of Carbonic Anhydrase XII (CAXII) in the migration of Dendritic Cells (DCs) and the interplay between CAXII and Hedgehog (Hh) pathway in the migration of melanoma cells, through new small molecules, especially under hypoxia. At first, we decided to study the relationship between the Hh pathway and CAXII, underlining their involvement in melanoma cell migration under hypoxia. Indeed, such signaling is well-known for its role in various physiological processes but aberrantly re-activated in cancer cells and carbonic anhydrases (CAs), key enzymes in pH regulation, have been linked to cell migration. In this study, we targeted components of the Hh pathway using Glabrescione B and C22, as well as Cyclopamine and SAG, to assess their impact on CAXII expression, particularly under hypoxic conditions. Migration and invasion assays were conducted on two melanoma cell lines, SK-MEL-28 and A375, where Smoothened, a pivotal upstream regulator of the Hh pathway, and GLI1, its primary transcription factor, were chemically inhibited. The findings revealed a connection between CAXII and the Hh pathway, demonstrating that their inhibition significantly impaired melanoma migration and invasion, especially under hypoxia. Then, due to the relevance of DCs in the TME and DCs-based immunotherapy in melanoma, we focused our attention on DCs with the aim to study CAXII expression and role. For the first time, we observed an increased expression of CAXII in mature DCs (stimulated with lipopolysaccharide, LPS) either under normoxia or hypoxia. To understand the involvement of CAXII in DC migration we first inhibited CAs with the chemical compound acetazolamide (AAZ), observing a downregulation of CAXII expression. We performed a migration assay in the presence of AAZ, observing a reduction in DC migration. In addition, to define if CAXII itself was crucial in DC migration, we knocked down the protein with a siRNA approach under normoxia and hypoxia, either in the presence or not of LPS. Finally, we performed a migration assay, demonstrating that CAXII siRNA significantly reduced DC migration under all experimental conditions. Overall, these data suggest a similar role of CAXII in two different cellular models highlighting its involvement in cell migration, specifically related to Hh pathway in melanoma cells, especially under hypoxic conditions. These findings acquire a major impact on the development of new therapeutical strategies targeting CAXII in a hypoxic microenvironment, a typical feature of physiological and pathological conditions

Detection of early age-related macular degeneration using novel functional parameters of the focal cone electroretinogram

The focal cone electroretinogram is a sensitive marker for macular disease, but have we unlocked its full potential? Typically assessment of waveform parameters is subjective and focuses on a small number of locations (e.g. the a-wave). This study evaluated the discriminatory and diagnostic potential of 4 conventional and 15 novel, objectively determined, parameters in patients with early Age-related Macular Degeneration. Focal cone electroretinograms were recorded in 54 participants with early Age-related Macular Degeneration (72.9±8.2 years) and 54 healthy controls (69±7.7 years). Conventional a and b wave amplitudes and implicit times were measured and compared to novel parameters derived from both the 1st and 2nd derivatives and the frequency-domain power spectrum of the electroretinogram.Statistically significant differences between groups were shown for all conventional parameters, the majority of 1st and 2nd derivative parameters and the power spectrum at 25 and 30 Hz. Receiver operating characteristics showed that both conventional and 1st and 2nd derivative implicit times had provided the best diagnostic potential. A regression model showed a small improvement over any individual parameter investigated. The non-conventional parameters enhanced the objective evaluation of the focal electroretinogram, especially when the amplitude was low. Furthermore, the novel parameters described here allow the implicit time of the electroretinogram to be probed at points other than the peaks of the a and b waves. Consequently these novel analysis techniques could prove valuable in future electrophysiological investigation, detection and monitoring of Age-related Macular Degeneration

Visual responses in a transplanted eye: reality or chimera?

not needed for Letters to the Edito

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