Nanostructured coatings for intraocular devices with drug delivery function

Despite numerous scientific research efforts, ocular drug delivery remains a challenge for scientists due to the problems related to the current methods that are 90% based on eye drops administration. This therapeutics has some limitations such as rapid drug loss, toxic effects on ocular surfaces and poor patient compliance with the drug regimen. Due to these limitations the current research is focused on the development of newer systems for delivery of the ophthalmic drugs. Nanotechnology-based drug delivery can improve viable solutions giving multiple functionalities to the devices that are inserted in the eye. For example, glaucoma is one of the most troubling chronic diseases, globally considered the second leading cause of blindness by the World Health Organization, whose treatment requires drug administration during years or even during all life. It is therefore imperative to develop alternative therapeutics to administer the drugs into the eye. We are developing a new strategy to deliver the drugs for the glaucoma treatment using biocompatible and nanostructured surfaces that can be used as a coating in an intraocular device. The design of these drug delivery biocompatible surfaces involves the control of its molecular structure and functionality. We have been using Scanning Tunneling Microscopy (STM) at the solid/liquid interface[1-3] to add the components of the monolayers, step-by-step, controlling their adsorption in real time. We used this method to built nanostructured coatings composed of glycosaminoglycans adsorbed on Highly Oriented Pyrolitc Graphite (HOPG). Molecular resolution images were obtained during the formation of the monolayer that revealed a well-packed and organized surface. Presently, we are using these monolayers to adsorb a drug for glaucoma treatment encapsulated in a nanocarrier. Drug release kinetic studies monitored by UV-spectroscopy are underway and preliminary results suggest that this monolayer is very stable and that it is possible to control the drug release as a function of time.info:eu-repo/semantics/publishedVersio

A Highly Sensitive Potentiometric Amphetamine Microsensor Based on All-Solid-State Membrane Using a New Ion-Par Complex, [3,3′-Co(1,2-closo-C2B9H11)2]− C9H13NH+

In the present work a highly sensitive ion-selective microelectrode for the detection of amphetamine is presented. For this purpose, a novel ion-par complex based on the metallocarborane, cobalt bis(dicarbollide) anion ([3,3′-Co(1,2-C2B9H11)2]−) coupled to amphetamonium cation has been prepared as the active site for amphetamine recognition. The prepared ion-par complex was incorporated to a PVC-type sensitive membrane. It was then drop-casted on the top of a gold microelectrode previously modified with a solid contact layer of polypyrrole. This novel amphetamine microsensor has provided excellent and quick response within the range 10−5 M to 10−3 M of amphetamine concentration, a limit of detection of 12 µM and a slope of 60.1 mV/decade. It was also found to be highly selective toward some potential interference compounds when compared to amphetamine.The authors acknowledge the financial support from the European Union’s Horizon 2020 research and innovation programme entitled MicroMole and HEARTEN grant agreement No. 653626 and No. 643694 respectivel

Water resources management in southern Europe : clues for a research and innovation based regional hypercluster

European countries are facing increasing pressures on their water resources despite stringent regulations and systematic efforts on environmental protection. In this context, research and innovation play a strategic role reinforcing the efficiency of water policies. The present study provides a multilevel assessment of research and innovation practices in the field of water resource management in southern European countries and regions (more specifically; Cyprus, Albania, Poitou-Charentes in France, Andalusia in Spain and the North of Portugal). The analysis was based on a strategic framework aimed at gaining an insight of the current constraints, as well as of the existing and future technological solutions for a better water resource management. The triple helix model proved to be a useful analytical framework for assessing the efforts of different groups towards a common goal. The analysis proved the existence of a significant evolution in the use of technological tools to assist decision-making processes in integrated river basin management in all regions. Nevertheless, the absence of formal channels for knowledge and data exchange between researchers and water resource managers complicates the formers involvement in the decision-making process regarding water allocation. Both researchers and consultants emphasize the low availability of data, together with the need to advance on water resource economics as relevant constraints in the field. The SWOT analysis showed similar concerns among the participating regions and provided a battery of effective projects that resulted in the preparation of a Joint Action Plan.The authors are grateful to all stakeholders that contributed, either by completing the online survey, either by personal interview, as well as to the external evaluators, who contributed to the methodological validation. The authors are also indebted to Alexandrina Rodrigues, Daniel Ribeiro and Teresa Tavares for the manuscript revision. The authors acknowledge NOVIWAM project partners for their valuable comments and contributions, as well as the funding provided by the European Union under the 7th Framework Programme for Research and Technological Development (Grant Agreement no 245460)

a dynamic model of firms strategic location choice

This paper analyzes the optimal location choice of a firm in a dynamic Cournot framework, in which firms' absorptive capacities may depend on their knowledge stock. The firm decides whether to locate irreversibly in a cluster or in isolation. In the cluster the firm benefits from inward spillovers from its competitors, but also generates outward spillovers. If the firm chooses to locate in isolation no knowledge flows occur. All firms' production costs are determined by their knowledge stocks, which evolve over time due to own R&D investments and potentially inward spillovers. It is shown that, if absorptive capacity is constant, the incentive to locate in the cluster decreases with respect to the firm's knowledge stock. Conversely, if absorptive capacity depends positively on knowledge stock, the firm's incentive to join the cluster is larger the more knowledge it has. It is also shown that qualitative properties of the equilibrium paths of R&D investments and knowledge stocks differ substantially depending on whether absorptive capacities are constant or knowledge dependent

Glucocorticoid receptor antagonism overcomes resistance to BRAF inhibition in BRAFV600E-mutated metastatic melanoma

Clinical applications of glucocorticoids (GC) in Oncology are dependent on their pro-apoptotic action to treat lymphoproliferative cancers, and to alleviate side effects induced by chemotherapy and/or radiotherapy. However, the mechanism(s) by which GC may also promote tumor progression remains unclear. GC receptor (GR) knockdown decreases the antioxidant protection of highly metastatic B16-F10 melanoma cells. We hypothesize that a GR antagonist (RU486, mifepristone) could increase the efficacy of BRAF-related therapy in BRAFV600E-mutated metastatic melanoma. In vivo formed spontaneous skin tumors were reinoculated into nude mice to expand the metastases of different human BRAFV600E melanoma cells. The GR content of melanoma cell lines was measured by [3H]-labeled ligand binding assay. Nuclear Nrf2 and its transcription activity was investigated by RT-PCR, western blotting, and by measuring Nrf2- and redox state-related enzyme activities and metabolites. GR knockdown was achieved using lentivirus, and GR overexpression by transfection with the NR3C1 plasmid. shRNA-induced selective Bcl-xL, Mcl-1, AKT1 or NF-κB/p65 depletion was used to test the efficacy of vemurafenib (VMF) and RU486 against BRAFV600E-mutated metastatic melanoma. During early progression of skin melanoma metastases, RU486 and VMF induced a drastic metastases regression. However, treatment at an advanced stage of growth demonstrated the development of resistance to RU486 and VMF. This resistance was mechanistically linked to overexpression of specific proteins of the Bcl-2 family (Bcl-xL and Mcl-1 in our experimental models). We found that melanoma resistance is decreased if AKT and NF-κB signaling pathways are blocked. Our results highlight mechanisms by which metastatic melanoma cells adapt to survive

Impacto de un programa de recuperación intensificada en cistectomía radical. Estudio comparativo de cohortes

Objetivo: Evaluar los resultados de la instauración de un programa de recuperación intensificada (ERAS) para cistectomía radical en abordaje abierto con respecto a la cohorte histórica de un mismo hospital. Material y métodos: Estudio de análisis retrospectivo de 138 pacientes sometidos a cistectomía radical con derivación ileal tipo Bricker o Studer de forma consecutiva (97 históricos vs. 41 ERAS). Se compararon tasa de complicaciones a 30 días, complicaciones estadio Clavien-Dindo > 2, mortalidad, estancia y tasa de readmisión en el hospital y en cuidados críticos, reintervención y necesidad de sondaje nasogástrico, trasfusión o nutrición parenteral. Resultados: No se hallaron diferencias estadísticamente significativas en cuanto a la tasa de complicaciones globales tras 30 días de alta (73,171 vs. 77.32%; OR 1,25, IC 95% 0,54-2,981; p = 0,601) ni en Clavien-Dindo > 2 (41,463 vs. 42.268%; OR 1.033, IC 95% 0,492-2,167; p = 0,93), así como en mortalidad, estancias o tasas de readmisión y reintervención. La necesidad de sondaje nasogástrico fue menor en el grupo ERAS (43,902 vs. 78,351%; OR 4,624, IC 95% 2,112-10,123; p < 0,0001), así como la necesidad de nutrición parenteral total (26,829 vs. 34,021%; OR 12,234, IC 95% 5,165-28,92; p < 0,0001) y el tiempo bajo intubación orotraqueal desde la inducción anestésica (mediana [RIC] = 325 (285-355) vs. 540 (360-600) min; p < 0,0001). Conclusión: Los programas de recuperación intensificada en cistectomía radical disminuyen el intervencionismo sobre el paciente sin aumentar la morbimortalidad

NOVIWAM : Five European countries together for improving water quality and water use efficiency

The European NOVIWAM (NOvel Integrated Water Management Systems for Southern European Regions, www.noviwam.eu) program aims to promote interregional co-operation in the field of water management tools and methods. One of its originality is to analyze in depth the relations between decision makers, stakeholders and researchers in order to disseminate know-how and technologies, and to tackle the compelling water management problems faced in the Euro-Mediterranean climate regions. In a first period, aiming at a good ecological and chemical state of waters and at a sustainable and efficient resource management, five European countries/regions (Albania, Cyprus, Poitou-Charentes in France, Northern Region in Portugal and Andalusia in Spain) are working together. The program will thus contribute to the objectives of the European Water Framework Directive. But additionally, the NOVIWAM program will establish a schedule for the implementation of a « Join action plan », trying to involve other countries into it, and generalize the conclusions of this three year work at a regional and international level.NOVIWAM (Grant Agreement nº 245460

knowledge spillovers congestion effects and long run location patterns

We introduce an evolutionary two-country model to characterize long run location patterns of the manufacturing activities of competing multinational enterprises. Firms located in country 1 can decide to offshore their manufacturing activities to country 2. The profitability of production in a country depends on several factors: unitary costs of production, the number of firms that are located in each country, within-country spillovers, and cross-border spillovers. Furthermore, profits in country 2 are influenced by congestion costs. Country 1 is assumed to be technologically advanced and has an advantage in terms of internal spillovers. In contrast, country 2 offers lower production unit cost which, however, may be offset by congestion costs. The firms' (re)location choices are based on a simple comparison of current production costs obtained in the two countries and the dynamics of switching is modeled by a simple replicator dynamics. The global analysis of the resulting one-dimensional dynamical system reveals that a large advantage in terms of unitary production costs encourages the firms to off-shore manufacturing activities to country 2. This off-shoring process stops when congestion costs offset this advantage of country 2, even though congestion costs do not cause all manufacturing activities to be re-shored to country 1. The re-shoring process can be accelerated by an increase of within-country spillovers in country 1, while cross-border spillovers tend to favor a geographic dispersion of manufacturing activities and make location patterns that lead to suboptimal long run outcomes less likely

Global delivery models: the role of talent, speed and time zones in the global outsourcing industry

Global delivery models (GDMs) are transforming the global IT and business process outsourcing industry. GDMs are a new form of client-specific investment promoting service integration with clients by combining client proximity with time-zone spread for 24/7 service operations. We investigate antecedents and contingencies of setting up GDM structures. Based on comprehensive data we show that providers are likely to establish GDM location configurations when clients value access to globally distributed talent and speed of service delivery, in particular when services are highly commoditized. Findings imply that coordination across time zones increasingly affects international operations in business-to-business and born-global industries

Home-owned versus foreign-owned firms in the UK automotive industry : exploring the microfoundations of ambidextrous production and supply chain positioning

The UK automotive industry is home to a large number of foreign firms, demonstrating the open nature of competition. However, the industry necessitates both exploitative and explorative capabilities. Contingency theory suggests that firms align their internal structure with contextual factors. As such, the aims of this study were to investigate whether it was possible to distinguish home-owned (UK) and foreign-owned firms based upon: a) the microfoundations of ambidextrous production, which are conceptualised as lean and agile routines; and b) the tier at which these firms operate in the automotive supply chain. Survey data were collected from 85 home-owned and 55 foreign-owned firms within the UK Midlands automotive industry. Logistic regression results revealed that home-owned firms were significantly more likely to be implementing explorative (agile) production methods, whereas foreign-owned firms were significantly more likely to be implementing exploitative (lean) production. Home-owned and foreign-owned firms were found to be significantly more likely to be operating upstream and downstream in the automotive supply chain respectively. Thus, the findings support a contingency theory explanation, suggesting that firms align their performance priorities with contextual factors, but we argue that home-owned and foreign-owned firms have evolved to compete based on their different innovative capabilities, which are located at different tiers of the automotive supply chain. On this basis, although neither home-owned nor foreign-owned firms were found to be endogenously ambidextrous, we argue that foreign-owned firms internationalise into the UK automotive sector to exploit the explorative capabilities acquired by home-owned firms operating upstream in automotive supply chains, thus enabling ambidextrous capabilities at an exogenous, industrial level