Intraocular implants for extended drug delivery: therapeutic applications.

An overview of ocular implants with therapeutic application potentials is provided. Various types of implants can be used as slow release devices delivering locally the needed drug for an extended period of time. Thus, multiple periocular or intraocular injections of the drug can be circumvented and secondary complications minimized. The various compositions of polymers fulfilling specific delivery goals are described. Several of these implants are undergoing clinical trials while a few are already commercialized. Despite the paramount progress in design, safety and efficacy, the place of these implants in our clinical therapeutic arsenal remains limited. Miniaturization of the implants allowing for their direct injection without the need for a complicated surgery is a necessary development avenue. Particulate systems which can be engineered to target specifically certain cells or tissues are another promising alternative. For ocular diseases affecting the choroid and outer retina, transscleral or intrasscleral implants are gaining momentum.

Improved flooding of broadcast messages using extended multipoint relaying

A common operation in wireless ad hoc networks is the flooding of broadcast messages to establish network topologies and routing tables. The flooding of broadcast messages is, however, a resource consuming process. It might require the retransmission of messages by most network nodes. It is, therefore, very important to optimize this operation. In this paper, we first analyze the multipoint relaying (MPR) flooding mechanism used by the Optimized Link State Routing (OLSR) protocol to distribute topology control (TC) messages among all the system nodes. We then propose a new flooding method, based on the fusion of two key concepts: distance-enabled multipoint relaying and connected dominating set (CDS) flooding. We present experimental simulationsthat show that our approach improves the performance of previous existing proposals.

New evidence of neuroprotection by lactate after transient focal cerebral ischaemia: extended benefit after intracerebroventricular injection and efficacy of intravenous administration.

BACKGROUND: Lactate protects mice against the ischaemic damage resulting from transient middle cerebral artery occlusion (MCAO) when administered intracerebroventricularly at reperfusion, yielding smaller lesion sizes and a better neurological outcome 48 h after ischaemia. We have now tested whether the beneficial effect of lactate is long-lasting and if lactate can be administered intravenously. METHODS: Male ICR-CD1 mice were subjected to 15-min suture MCAO under xylazine + ketamine anaesthesia. Na L-lactate (2 µl of 100 mmol/l) or vehicle was administered intracerebroventricularly at reperfusion. The neurological deficit was evaluated using a composite deficit score based on the neurological score, the rotarod test and the beam walking test. Mice were sacrificed at 14 days. In a second set of experiments, Na L-lactate (1 µmol/g body weight) was administered intravenously into the tail vein at reperfusion. The neurological deficit and the lesion volume were measured at 48 h. RESULTS: Intracerebroventricularly injected lactate induced sustained neuroprotection shown by smaller neurological deficits at 7 days (median = 0, min = 0, max = 3, n = 7 vs. median = 2, min = 1, max = 4.5, n = 5, p < 0.05) and 14 days after ischaemia (median = 0, min = 0, max = 3, n = 7 vs. median = 3, min = 0.5, max = 3, n = 7, p = 0.05). Reduced tissue damage was demonstrated by attenuated hemispheric atrophy at 14 days (1.3 ± 4.0 mm(3), n = 7 vs. 12.1 ± 3.8 mm(3), n = 5, p < 0.05) in lactate-treated animals. Systemic intravenous lactate administration was also neuroprotective and attenuated the deficit (median = 1, min = 0, max = 2.5, n = 12) compared to vehicle treatment (median = 1.5, min = 1, max = 8, n = 12, p < 0.05) as well as the lesion volume at 48 h (13.7 ± 12.2 mm(3), n = 12 vs. 29.6 ± 25.4 mm(3), n = 12, p < 0.05). CONCLUSIONS: The beneficial effect of lactate is long-lasting: lactate protects the mouse brain against ischaemic damage when supplied intracerebroventricularly during reperfusion with behavioural and histological benefits persisting 2 weeks after ischaemia. Importantly, lactate also protects after systemic intravenous administration, a more suitable route of administration in a clinical emergency setting. These findings provide further steps to bring this physiological, commonly available and inexpensive neuroprotectant closer to clinical translation for stroke.

Strategic investment appraisal; extended real options approach

Tutkielma keskittyy lisäämään investointiarviointiprosessien rationaalisuutta strategisten investointien arvioinnissa duopoli- / oligopolimarkkinoilla. Tutkielman päätavoitteena on selvittää kuinka peliteorialla laajennettu reaalioptioperusteinen investointien arviointimenetelmä, laajennettu reaalioptiokehikko, voisi mahdollisesti parantaa analyysien tarkkuutta. Tutkimus lähestyy ongelmaa investoinnin ajoituksen sekä todellisten investoinnin arvoattribuuttien riippuvuuksien kautta. Laajennettu reaalioptiokehikko on investointien analysointi- ja johtamistyökalu, joka tarjoaa osittain rajoitetun (sisältää tällä hetkellä ainoastaan parametrisen ja peliteoreettisen epävarmuuden) optimaalisen arvovälin investoinnin todellisesta arvosta. Kehikossa, ROA kartoittaa mahdolliset strategiset hyödyt tunnistamalla investointiinliittyvät eri optiot ja epävarmuudet, peliteoria korostaa ympäristön luomia paineita investointiin liittyvän epävarmuuden hallitsemisessa. Laajennettu reaalioptiokehikko tarjoaa rationaalisemman arvion strategisen investoinnin arvosta, koska se yhdistää johdonmukaisemmin option toteutuksen ja siten myös optioiden aika-arvon, yrityksen todellisiin rajoitettuihin (rajoituksena muiden markkinatoimijoiden toimet) polkuriippuvaisiin kyvykkyyksiin.

The Boundaries of the Firm from the Extended Transaction Cost Economics Point of View - Empirical Study

Tutkimuksen tavoitteena oli tutkia yrityksen rajoja laajennetun transaktiokustannusteorian näkökulmasta. Tutkimus oli empiirinen tutkimus, jossa tutkittiin viittä toimialaa. Tutkimuksen tavoitteena oli verrata paperiteollisuutta teräs-, kemian-, ICT- ja energiateollisuuteen. Aineisto empiiriseen osioon kerättiin puolistrukturoiduilla teemahaastatteluilla. Tutkimus osoitti, että laajennettu transaktiokustannusteoria soveltuu hyvinyrityksen rajojen määrittelyyn. Staattinen transaktiokustannusteorian selitysaste ei ole riittävä, joten dynaaminen laajennus on tarpeellinen. Tutkimuksessa ilmeni, että paperiteollisuudella verrattuna muihin toimialoihin on suurimmat haasteet tehokkaiden rajojen määrittämisessä.

Value added logistics in supply and demand chains. Smile. Part 1. eBusiness between global company and itslocal sme supplier network

VALOSADE (Value Added Logistics in Supply and Demand Chains) is the research project of Anita Lukka's VALORE (Value Added Logistics Research) research team inLappeenranta University of Technology. VALOSADE is included in ELO (Ebusiness logistics) technology program of Tekes (Finnish Technology Agency). SMILE (SME-sector, Internet applications and Logistical Efficiency) is one of four subprojects of VALOSADE. SMILE research focuses on case network that is composed of small and medium sized mechanical maintenance service providers and global wood processing customers. Basic principle of SMILE study is communication and ebusiness insupply and demand network. This first phase of research concentrates on creating backgrounds for SMILE study and for ebusiness solutions of maintenance case network. The focus is on general trends of ebusiness in supply chains and networksof different industries; total ebusiness system architecture of company networks; ebusiness strategy of company network; information value chain; different factors, which influence on ebusiness solution of company network; and the correlation between ebusiness and competitive advantage. Literature, interviews and benchmarking were used as research methods in this qualitative case study. Networks and end-to-end supply chains are the organizational structures, which can add value for end customer. Information is one of the key factors in these decentralized structures. Because of decentralization of business, information is produced and used in different companies and in different information systems. Information refinement services are needed to manage information flows in company networksbetween different systems. Furthermore, some new solutions like network information systems are utilised in optimising network performance and in standardizingnetwork common processes. Some cases have however indicated, that utilization of ebusiness in decentralized business model is not always a necessity, but value-add of ICT must be defined case-specifically. In the theory part of report, different ebusiness and architecture models are introduced. These models are compared to empirical case data in research results. The biggest difference between theory and empirical data is that models are mainly developed for large-scale companies - not for SMEs. This is due to that implemented network ebusiness solutions are mainly large company centered. Genuine SME network centred ebusiness models are quite rare, and the study in that area has been few in number. Business relationships between customer and their SME suppliers are nowadays concentrated more on collaborative tactical and strategic initiatives besides transaction based operational initiatives. However, ebusiness systems are further mainly based on exchange of operational transactional data. Collaborative ebusiness solutions are in planning or pilot phase in most case companies. Furthermore, many ebusiness solutions are nowadays between two participants, but network and end-to-end supply chain transparency and information systems are quite rare. Transaction volumes, data formats, the types of exchanged information, information criticality,type and duration of business relationship, internal information systems of partners, processes and operation models (e.g. different ordering models) differ among network companies, and furthermore companies are at different stages on networking and ebusiness readiness. Because of former factors, different customer-supplier combinations in network must utilise totally different ebusiness architectures, technologies, systems and standards.

Content value chains modelling using a copyright ontology

Existing digital rights management (DRM) systems, initiatives like Creative Commons or research works as some digital rights ontologies provide limited support for content value chains modelling and management. This is becoming a critical issue as content markets start to profit from the possibilities of digital networks and the World Wide Web. The objective is to support the whole copyrighted content value chain across enterprise or business niches boundaries. Our proposal provides a framework that accommodates copyright law and a rich creation model in order to cope with all the creation life cycle stages. The dynamic aspects of value chains are modelled using a hybrid approach that combines ontology-based and rule-based mechanisms. The ontology implementation is based on Web Ontology Language and Description Logic (OWL-DL) reasoners, are directly used for license checking. On the other hand, for more complex aspects of the dynamics of content value chains, rule languages are the choice.

Kineettinen tarkastelu keskisakeusalueella toimivalle happivaiheelle

Työn tavoitteena oli tarkastella keskisakeudessa toimivan happidelignifioinnin kinetiikkaa ja vertailla sitä olemassa olevien kineettisten tutkimuksien kanssa. Lisäksi tutkittiin kuinka happivaiheen suodos vaikuttaa delignifiointiasteeseen sekä selektiivisyyteen. Työn kirjallisuusosassa perehdyttiin happidelignifioinnin kineettisiin malleihin, jotka on kehitetty ennustamaan alkalin, paineen, lämpötilan ja ajan vaikutusta ligniinin poistumiselle sekä hiilihydraattiketjujen katkeilulle. Delignifioituminen on nopeaa ensimmäisen kymmenen minuutin aikana ja hidastuu jäännösdelignifiointivaiheessa. Laboratoriotutkimuksissa selvitettiin kuinka prosessimuuttujat vaikuttavat kappaluvun ja viskositeetin muutokseen. Tuloksia tarkasteltiin lineaarisella regressioanalyysillä, jonka avulla muuttujien vaikutukset saadaan selkeästi esille. Happivaiheen ensimmäisessä vaiheessa suurin vaikutus delignifiointiasteeseen sekä viskositeetin alenemiseen on alkaliannoksella. Pienillä hapen annostuksella saavutettiin hyvä selektiivisyys, suurillakin alkaliannoksilla. Lämpötilan vaikutus on lähes olematon, kun paine on pieni. Kun paine kasvaa, kasvaa myös lämpötilan vaikutus delignifiointiasteeseen. Hiilihydraattien depolymerisoituminen lisääntyy lämpötilan kasvaessa lähes lineaarisesti, riippumatta paineesta. Hyvä loppuselektiivisyys saavutetaan kun ensimmäisen vaiheen selektiivisyys on hyvä. Ensimmäisessä vaiheessa saavutettiin hyvä selektiivisyys, kun alkali ei pääse kulumaan loppuun eikä delignifioituminen jatku liian pitkälle. Toisessa vaiheessa selektiivisyys säilyy parhaiten, kun lisättävä alkaliannos on pieni. Lämpötila ja paine vaikuttavat alkaliannokseen verrattuna hyvin vähän loppuselektiivisyyteen.

Easy introduction of maleimides at different positions of oligonucleotide chains for conjugation purposes

[2,5-Dimethylfuran]-protected maleimides were placed at both internal positions and the 3'-end of oligonucleotides making use of solid-phase synthesis procedures. A new phosphoramidite derivative and a new solid support incorporating the protected maleimide moiety were prepared for this purpose. In all cases maleimide deprotection (retro-Diels-Alder reaction) followed by reaction with thiol-containing compounds afforded the target conjugate.

'And the best essay is...' : Extended contact and cross-group friendships at school

We conducted one experimental intervention based on extended contact principles aimed at fostering the formation of cross-group friendships within educational settings. Italian school children took part in a school competition for the best essay on personal experiences of cross-group friendships with immigrants, to be written in small groups. This manipulation was intended to favour the exchange of personal positive cross-group experiences, thus capitalizing on the benefits of extended contact. In the control condition, participants wrote an essay on friendship, without reference to cross-group relations. Results revealed that children who took part in the intervention reported a higher number of outgroup friends 3 months later. This indirect effect was sequentially mediated by pro-contact ingroup and outgroup norms and by outgroup contact behavioural intentions. This study provides experimental evidence that interventions based on extended contact can foster cross-group friendship formation. Theoretical and practical implications of the findings are discussed.

Extended Endoscopic Endonasal Approaches for Cerebral Aneurysms: Anatomical, Virtual Reality and Morphometric Study

Introduction. The purpose of the present contribution is to perform a detailed anatomic and virtual reality three-dimensional stereoscopic study in order to test the effectiveness of the extended endoscopic endonasal approaches for selected anterior and posterior circulation aneurysms. Methods. The study was divided in two main steps: (1) simulation step, using a dedicated Virtual Reality System (Dextroscope, Volume Interactions); (2) dissection step, in which the feasibility to reach specific vascular territory via the nose was verified in the anatomical laboratory. Results. Good visualization and proximal and distal vascular control of the main midline anterior and posterior circulation territory were achieved during the simulation step as well as in the dissection step (anterior communicating complex, internal carotid, ophthalmic, superior hypophyseal, posterior cerebral and posterior communicating, basilar, superior cerebellar, anterior inferior cerebellar, vertebral, and posterior inferior cerebellar arteries). Conclusion. The present contribution is intended as strictly anatomic study in which we highlighted some specific anterior and posterior circulation aneurysms that can be reached via the nose. For clinical applications of these approaches, some relevant complications, mainly related to the endonasal route, such as proximal and distal vascular control, major arterial bleeding, postoperative cerebrospinal fluid leak, and olfactory disturbances must be considered

Electron scattering in isotonic chains as a probe of the proton shell structure of unstable nuclei

Electron scattering on unstable nuclei is planned in future facilities of the GSI and RIKEN upgrades. Motivated by this fact, we study theoretical predictions for elastic electron scattering in the N=82, N=50, and N=14 isotonic chains from very proton-deficient to very proton-rich isotones. We compute the scattering observables by performing Dirac partial-wave calculations. The charge density of the nucleus is obtained with a covariant nuclear mean-field model that accounts for the low-energy electromagnetic structure of the nucleon. For the discussion of the dependence of scattering observables at low-momentum transfer on the gross properties of the charge density, we fit Helm model distributions to the self-consistent mean-field densities. We find that the changes shown by the electric charge form factor along each isotonic chain are strongly correlated with the underlying proton shell structure of the isotones. We conclude that elastic electron scattering experiments on isotones can provide valuable information about the filling order and occupation of the single-particle levels of protons.

Care delivery value chains for ophthalmic clinics in Switzerland

Perceived patient value is often not aligned with the emerging expenses for health care services. In other words, the costs are often supposed as rising faster than the actual value for the patients. This fact is causing major concerns to governments, health plans, and individuals. Attempts to solve the problem have habitually been on the operational effectiveness side: increasing patient volume, minimizing costs, rationing, or closing hospitals, usually resulting in a zero-sum game. Only few approaches come from the strategic positioning side and "competition" among hospitals is still perceived rather as a danger than as a chance to create a positive-sum game and stimulate patient value. In their 2006 book, "Redefining Health Care", the renowned Harvard strategy professor Michael E. Porter and hospital management expert Professor Elizabeth Olmsted Teisberg approach the challenge from the positive-sum perspective: they propose to form Integrated Practice Units (IPUs) and manage hospitals in a modern, patient value oriented way. They argue that creating value-based competition on results should have the same effect on the health care sector like transparency and competition turned other industries with out-dated management models (like recently the inert telecommunication industry) into highly competitive and customer value creating businesses. The objective of this paper is to elaborate Care Delivery Value Chains for Integrated Practice Units in ophthalmic clinics and gather a first feedback from Swiss hospital managers, ophthalmologists, and patients, if such an approach could be a realistic way to improve health care management. First, Porter's definition of competitiveness (distinction between operational effectiveness and strategic positioning) is explained. Then, the Care Delivery Value Chain is introduced as a key element for understanding value-based management, followed by three practice examples for ophthalmic clinics. Finally, recommendations are given how the Care Delivery Value Chain can be managed efficiently and how the obstacles of becoming a patient-oriented organization can be overcome. The conclusion is that increased transparency and value-based competition on results has the potential to change the mindset of hospital managers-which will align patient value with the emerging health care expenses. Early adapters of this management approach will gain a competitive advantage. [Author, p. 6]