efficiency and evolution of R&D Networks.

This work introduces a new model to investigate the efficiency and evolution of networks of firms exchanging knowledge in R&D partnerships. We first examine the efficiency of a given network structure from the point of view of maximizing total profits in the industry. We show that the efficient network structure depends on the marginal cost of collaboration. When the marginal cost is low, the complete graph is efficient. However, a high marginal cost implies that the efficient network is sparser and has a core-periphery structure. Next, we examine the evolution of the network structure when the decision on collaborating partners is decentralized. We show the existence of multiple equilibrium structures which are in general inefficient. This is due to (i) the path dependent character of the partner selection process, (ii) the presence of knowledge externalities and (iii) the presence of severance costs involved in link deletion. Finally, we study the properties of the emerging equilibrium networks and we show that they are coherent with the stylized facts on R&D networks.R&D networks;technology spillovers;network efficiency;network formation;

The Efficiency and Evolution of R&D Networks

This work introduces a new model to investigate the efficiency and evolution of networks of firms exchanging knowledge in R&D partnerships. We first examine the efficiency of a given network structure in terms of the maximization of total profits in the industry. We show that the efficient network structure depends on the marginal cost of collaboration. When the marginal cost is low, the complete graph is efficient. However, a high marginal cost implies that the efficient network is sparser and has a core-periphery structure. Next, we examine the evolution of the network struc- ture when the decision on collaborating partners is decentralized. We show the existence of mul- tiple equilibrium structures which are in general inefficient. This is due to (i) the path dependent character of the partner selection process, (ii) the presence of knowledge externalities and (iii) the presence of severance costs involved in link deletion. Finally, we study the properties of the emerg- ing equilibrium networks and we show that they are coherent with the stylized facts of R&D net- works.R&D networks, technology spillovers, network efficiency, network formation

Protection of Inter-ONU Connectivity in Advanced PON with Minimum Trenching Cost

High-capacity and low-cost Passive Optical Network (PON) is a competitive solution for demanding applications that require low latency and high availability (e.g., 5G fronthaul). Recent proposals show that strict latency requirements can be satisfied by directly connecting Optical Network Units (ONUs) through the Remote Node, in an architecture called Advanced PON. To ensure high reliability of inter-ONU connections against fiber cuts, in this paper we propose two protection schemes that implement path protection and link protection in the context of advanced PONs. Our numerical results show that path protection requires (4-13)% more trenching to place spatially disjoint backup fibers compared to link protection, but might still be practical because of lower equipment complexity

Pressure ulcers management: an economic evaluation

Introduction. Pressure ulcer management represents a growing problem for medical and social health care systems all over the world, particularly in European Union countries where the incidence of pressure ulcers in older persons (> 60 years of age) is predicted to rise. Objectives. The aim of this study was to provide evidence for the lower impact on economic resources of using advanced dressings for the treatment of pressure ulcers with respect to conventional simple dressings. Methods. Two different models of analysis, derived from Activity Based Costing and Health Technology Assessment, were used to measure, over a 30-day period, the direct costs incurred by pressure ulcer treatment for community-residing patients receiving integrated home care. Results. Although the mean cost per home care visit was higher in the advanced dressings patient group than in the simple dressings patient one (? 22.31 versus ? 16.03), analysis of the data revealed that the cost of using advanced dressings was lower due to fewer home care visits (22 versus 11). Conclusion. The results underline the fact that decision-makers need to improve their understanding of the advantages of taking a long-term view with regards to the purchase and use of materials. This could produce considerable savings of resources in addition to improving treatment efficacy for the benefit of patients and the health care system

The FXR agonist obeticholic acid inhibits the cancerogenic potential of human cholangiocarcinoma

Cholangiocarcinoma (CCA) is an aggressive cancer with high resistance to chemotherapeutics. CCA is enriched in cancer stem cells, which correlate with aggressiveness and prognosis. FXR, a member of the metabolic nuclear receptor family, is markedly down-regulated in human CCA. Our aim was to evaluate, in primary cultures of human intrahepatic CCA (iCCA), the effects of the FXR agonist obeticholic acid (OCA), a semisynthetic bile acid derivative, on their cancerogenic potential. Primary human iCCA cell cultures were prepared from surgical specimens of mucinous or mixed iCCA subtypes. Increasing concentrations (0–2.5 μM) of OCA were added to culture media and, after 3–10 days, effects on proliferation (MTS assay, cell population doubling time), apoptosis (annexin V-FITC/propidium iodide), cell migration and invasion (wound healing response and Matrigel invasion assay), and cancerogenic potential (spheroid formation, clonogenic assay, colony formation capacity) were evaluated. Results: FXR gene expression was downregulated (RT-qPCR) in iCCA cells vs normal human biliary tree stem cells (p < 0.05) and in mucinous iCCA vs mixed iCCA cells (p < 0.05) but was upregulated by addition of OCA. OCA significantly (p < 0.05) inhibited proliferation of both mucinous and mixed iCCA cells, starting at a concentration as low as 0.05 μM. Also, CDCA (but not UDCA) inhibited cell proliferation, although to a much lower extent than OCA, consistent with its different affinity for FXR. OCA significantly induced apoptosis of both iCCA subtypes and decreased their in vitro cancerogenic potential, as evaluated by impairment of colony and spheroid formation capacity and delayed wound healing and Matrigel invasion. In general, these effects were more evident in mixed than mucinous iCCA cells. When tested together with Gemcitabine and Cisplatin, OCA potentiated the anti-proliferative and pro-apoptotic effects of these chemotherapeutics, but mainly in mixed iCCA cells. OCA abolished the capacity of both mucinous and mixed iCCA cells to form colonies when administered together with Gemcitabine and Cisplatin. In subcutaneous xenografts of mixed iCCA cells, OCA alone or combined with Gemcitabine or Cisplatin markedly reduced the tumor size after 5 weeks of treatment by inducing necrosis of tumor mass and inhibiting cell proliferation. In conclusion, FXR is down-regulated in iCCA cells, and its activation by OCA results in anti-cancerogenic effects against mucinous and mixed iCCA cells, both in vitro and in vivo. The effects of OCA predominated in mixed iCCA cells, consistent with the lower aggressiveness and the higher FXR expression in this CCA subtype. These results, showing the FXR-mediated capacity of OCA to inhibit cholangiocarcinogenesis, represent the basis for testing OCA in clinical trials of CCA patients

Andreev reflection in Au/La_{2-x}Sr_{x}CuO_{4} point-contact junctions: separation between pseudogap and phase-coherence gap

We made point-contact measurements with Au tips on La_{2-x}Sr_{x}CuO_{4} samples with 0.08 < x < 0.20 to investigate the relationship between superconducting gap and pseudogap. We obtained junctions whose conductance curves presented typical Andreev reflection features at all temperatures from 4.2 K up to T_c^A close to the bulk T_c. Their fit with the BTK-Tanaka-Kashiwaya model gives good results if a (s+d)-wave gap symmetry is used. The doping dependence of the low temperature dominant isotropic gap component Delta_{s} follows very well the T_{c} vs. x curve. These results support the separation between the superconducting (Andreev) gap and the pseudogap measured by angle-resolved photoemission spectroscopy (ARPES) and tunneling.Comment: 4 pages, 5 eps figures, 1 table. SNS 2001 Conferenc

Towards a New System for the Assessment of the Quality in Care Pathways: An Overview of Systematic Reviews

Clinical or care pathways are developed by a multidisciplinary team of healthcare practitioners, based on clinical evidence, and standardized processes. The evaluation of their framework/content quality is unclear. The aim of this study was to describe which tools and domains are able to critically evaluate the quality of clinical/care pathways. An overview of systematic reviews was conducted, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses, using Medline, Embase, Science Citation Index, PsychInfo, CINAHL, and Cochrane Library, from 2015 to 2020, and with snowballing methods. The quality of the reviews was assessed with Assessment the Methodology of Systematic Review (AMSTAR-2) and categorized with The Leuven Clinical Pathway Compass for the definition of the five domains: processes, service, clinical, team, and financial. We found nine reviews. Three achieved a high level of quality with AMSTAR-2. The areas classified according to The Leuven Clinical Pathway Compass were: 9.7% team multidisciplinary involvement, 13.2% clinical (morbidity/mortality), 44.3% process (continuity-clinical integration, transitional), 5.6% financial (length of stay), and 27.0% service (patient-/family-centered care). Overall, none of the 300 instruments retrieved could be considered a gold standard mainly because they did not cover all the critical pathway domains outlined by Leuven and Health Technology Assessment. This overview shows important insights for the definition of a multiprinciple framework of core domains for assessing the quality of pathways. The core domains should consider general critical aspects common to all pathways, but it is necessary to define specific domains for specific diseases, fast pathways, and adapting the tool to the cultural and organizational characteristics of the health system of each country

Circulating levels of IL-1 family cytokines and receptors in Alzheimer's disease: new markers of disease progression?

BACKGROUND: Although the mechanisms underlying AD neurodegeneration are not fully understood, it is now recognised that inflammation could play a crucial role in the initiation and progression of AD neurodegeneration. A neuro-inflammatory network, based on the anomalous activation of microglial cells, includes the production of a number of inflammatory cytokines both locally and systemically. These may serve as diagnostic markers or therapeutic targets for AD neurodegeneration. METHODS: We have measured the levels of the inflammation-related cytokines and receptors of the IL-1 family in serum of subjects with AD, compared to mild cognitive impairment (MCI), subjective memory complaints (SMC), and normal healthy subjects (NHS). Using a custom-made multiplex ELISA array, we examined ten factors of the IL-1 family, the inflammation-related cytokines IL-1α, IL-1β, IL-18, and IL-33, the natural inhibitors IL-1Ra and IL-18BP, and the soluble receptors sIL-1R1, sIL-1R2, sIL-1R3, and sIL-1R4. RESULTS: The inflammatory cytokines IL-1α and IL-1β, their antagonist IL-1Ra, and their soluble receptor sIL-1R1 were increased in AD. The decoy IL-1 receptor sIL-1R2 was only increased in MCI. IL-33 and its soluble receptor sIL-1R4 were also significantly higher in AD. The soluble form of the accessory receptor for both IL-1 and IL-33 receptor complexes, sIL-1R3, was increased in SMC and even more in AD. Total IL-18 levels were unchanged, whereas the inhibitor IL-18BP was significantly reduced in MCI and SMC, and highly increased in AD. The levels of free IL-18 were significantly higher in MCI. CONCLUSIONS: AD is characterised by a significant alteration in the circulating levels of the cytokines and receptors of the IL-1 family. The elevation of sIL-1R4 in AD is in agreement with findings in other diseases and can be considered a marker of ongoing inflammation. Increased levels of IL-1Ra, sIL-1R1, sIL-1R4, and IL-18BP distinguished AD from MCI and SMC, and from other inflammatory diseases. Importantly, sIL-1R1, sIL-1R3, sIL-1R4, and IL-18BP negatively correlated with cognitive impairment. A significant elevation of circulating sIL-1R2 and free IL-18, not present in SMC, is characteristic of MCI and disappears in AD, making them additional interesting markers for evaluating progression from MCI to AD