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

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

First proof-of-principle of inorganic lead halide perovskites deposition by magnetron-sputtering

The present work reports the application of RF-magnetron sputtering technique to realize CsPbBr 3 70 nm thick films on glass substrate by means of a one-step procedure. The obtained films show highly uniform surface morphology and homogeneous thickness as evidenced by AFM and SEM investigations. XRD measurements demonstrate the presence of two phases: a dominant orthorhombic CsPbBr 3 and a subordinate CsPb 2 Br 5 . Finally, XPS data reveals surface bromine depletion respect to the stoichiometrical CsPbBr 3 composition, nevertheless photoluminescence spectroscopy results confirm the formation of a highly luminescent film. These preliminary results demonstrate that our approach could be of great relevance for easy fabrication of large area perovskite thin films. Future developments, based on this approach, may include the realization of multijunction solar cells and multicolor light emitting devices

Comparison between Ischemic and Hemorrhagic Strokes in Functional Outcome at Discharge from an Intensive Rehabilitation Hospital

Comparison studies on recovery outcomes in ischemic (IS) and hemorrhagic strokes (HS) have yielded mixed results. In this retrospective observational study of consecutive IS and HS patients, we aimed at evaluating functional outcomes at discharge from an intensive rehabilitation hospital, comparing IS vs. HS, analyzing possible predictors. Modified Rankin Scale (mRS) at discharge was the main outcome. Out of the 229 patients included (mean age 72.9 ± 13.9 years, 48% males), 81 had HS (35%). Compared with IS (n = 148), HS patients were significantly younger (75 ± 12.5 vs. 68.8 ± 15.4 years, p = 0.002), required longer hospitalizations both in acute (23.9 ± 36.7 vs. 35.2 ± 29.9 days, p = 0.019) and rehabilitation hospitals (41.5 ± 31.8 vs. 77.2 ± 51.6 days, p = 0.001), and had more severe initial clinical deficit (mean number of neurological impairments: 2.0 ± 1.1 vs. 2.6 ± 1.4, p = 0.001) and mRS scores at admission (p = 0.046). At discharge, functional status change, expressed as mRS, was not significantly different between IS and HS (F = 0.01, p = 0.902), nor was the discharge destination (p = 0.428). Age and clinical severity were predictors of functional outcome in both stroke types. On admission in an intensive rehabilitation hospital, HS patients presented a worse functional and clinical status compared to IS. Despite this initial gap, the two stroke types showed an overlapped trajectory of functional recovery, with age and initial stroke severity as the main prognostic factors

Mutation profile of BBS genes in patients with Bardet-Biedl syndrome : An Italian study

Background: Bardet-Biedl syndrome (BBS) is a rare inherited multisystemic disorder with autosomal recessive or complex digenic triallelic inheritance. There is currently no treatment for BBS, but some morbidities can be managed. Accurate molecular diagnosis is often crucial for the definition of appropriate patient management and for the development of a potential personalized therapy. Methods: We developed a next-generation-sequencing (NGS) protocol for the screening of the 18 most frequently mutated genes to define the genotype and clarify the mutation spectrum of a cohort of 20 BBS Italian patients. Results: We defined the causative variants in 60% of patients; four of those are novel. 33% of patients also harboured variants in additional gene/s, suggesting possible oligogenic inheritance. To explore the function of different genes, we looked for correlations between genotype and phenotype in our cohort. Hypogonadism was more frequently detected in patients with variants in BBSome proteins, while renal abnormalities in patients with variations in BBSome chaperonin genes. Conclusions: NGS is a powerful tool that can help understanding BBS patients' phenotype through the identification of mutations that could explain differences in phenotype severity and could provide insights for the development of targeted therapy. Furthermore, our results support the existence of additional BBS loci yet to be identified

In vitro cell culture of amniotic fluid keratinocytes on amniotic membrane: the ideal tissue for repairing skin ulcers

OBJECTIVE: The amniotic fluid contains a large population of stem keratinocytes demonstrating minimal immunological rejection. Recent evidence suggests that stem cells from the amniotic fluid can be employed in the field of tissue engineering. In this work we identified precursors of the epithelial cells and expanded them in vitro.MATERIALS AND METHODS: After collecting samples of amniotic fluid and separating the cells via centrifugation, we seeded a portion of these cells in selection media to analyze the proliferation of epithelial cells. The stem cells precursors of keratinocytes were identified through specific markers. The expression of these markers was evaluated by immunofluorescence and reverse transcription polymerase chain reaction (PCR).RESULTS: The stem cells demonstrated 90% confluence, after undergoing proliferation in the selection medium for 15 days. Most of these cells tested positive for the keratinocyte-specific markers, but negative for stem cell specific markers. Of note, the identity of the keratinocytes was well established even after several subcultures.CONCLUSIONS: These results suggested that it is feasible to isolate and expand differentiated cell populations in the amniotic fluid from precursor cells. Furthermore, amniotic membranes can be utilized as scaffolds to grow keratinocytes, which can be potentially exploited in areas of skin ulcer transplantation and tissue engineering interventions

Macular impairment in fabry disease: A morpho-functional assessment by swept-source OCT angiography and focal electroretinography

PURPOSE. Fabry disease (FD) is a multiorgan X-linked condition characterized by a deficiency of the lysosomal enzyme alpha-galactosidase A, resulting in a progressive intralysosomal deposit of globotriaosylceramide. The aim of this study was to evaluate the macular ultrastructure of the vascular network using optical coherence tomography angiography (OCTA) and to evaluate macular function using focal electroretinography (fERG) in Fabry patients (FPs). METHODS. A total of 20 FPs (38 eyes, mean age 57 \ub1 2.12 SD, range of 27\u201380 years) and 17 healthy controls (27 eyes, mean age 45 years \ub1 20.50 SD, range of 24\u201365 years) were enrolled in the study. Color fundus photography, swept-source optical coherence tomography (SS-OCT), OCTA and fERG were performed in all subjects. The OCTA foveal avascular zone (FAZ), vasculature structure, superficial and deep retinal plexus densities (images of 4.5 X 4.5 mm) and fERG amplitudes were measured. Group differences were statistically assessed by Student\u2019s t-test and ANOVA. RESULTS. In the FP group, the FAZ areas of the superficial and deep plexuses were enlarged (P = 0.036, t = 2.138; P < 0.001, t = 3.889, respectively), the vessel density was increased in the superficial plexus, and the fERG amplitude was reduced (P < 0.001, t = 10.647) compared with those in healthy controls. No significant correlations were found between the structural and functional data. CONCLUSIONS. OCTA vascular abnormalities and reduced fERG amplitudes indicate subclinical signs of microangiopathy with early retinal dysfunction in FPs. This study highlights the relevance of OCTA imaging analysis in the identification of abnormal macular vasculature as an ocular hallmark of FD

Linear, Non-Conjugated Cyclic and Conjugated Cyclic Paraphenylene under Pressure

The n-paraphenylene family comprises chains of phenylene units linked together by C-C bonds that are between single- and double-bonded, and where n corresponds to the number of phenylene units. In this work, we compare the response of the optical properties of different phenylene arrangements. We study linear chains (LPP), cyclic systems (CPPs), and non-conjugated cyclic systems with two hydrogenated phenylenes (H4[n]CPP). Particularly, the systems of interest in this work are [6]LPP, [12]- and [6]CPP and H4[6]CPP. This work combines Raman and infrared spectroscopies with absorption and fluorescence (one- and two-photon excitations) measured as a function of pressure up to maximum of about 25 GPa. Unprecedented crystallographic pressure-dependent results are shown on H4[n]CPP, revealing intramolecular ¿-¿ interactions upon compression. These intramolecular interactions justify the H4[n]CPP singular optical properties with increasing fluorescence lifetime as a function of pressure