Design and optimization of components and processes for plasma sources in advanced material treatments

The research activities described in the present thesis have been oriented to the design and development of components and technological processes aimed at optimizing the performance of plasma sources in advanced in material treatments. Consumables components for high definition plasma arc cutting (PAC) torches were studied and developed. Experimental activities have in particular focussed on the modifications of the emissive insert with respect to the standard electrode configuration, which comprises a press fit hafnium insert in a copper body holder, to improve its durability. Based on a deep analysis of both the scientific and patent literature, different solutions were proposed and tested. First, the behaviour of Hf cathodes when operating at high current levels (250A) in oxidizing atmosphere has been experimentally investigated optimizing, with respect to expected service life, the initial shape of the electrode emissive surface. Moreover, the microstructural modifications of the Hf insert in PAC electrodes were experimentally investigated during first cycles, in order to understand those phenomena occurring on and under the Hf emissive surface and involved in the electrode erosion process. Thereafter, the research activity focussed on producing, characterizing and testing prototypes of composite inserts, combining powders of a high thermal conductibility (Cu, Ag) and high thermionic emissivity (Hf, Zr) materials The complexity of the thermal plasma torch environment required and integrated approach also involving physical modelling. Accordingly, a detailed line-by-line method was developed to compute the net emission coefficient of Ar plasmas at temperatures ranging from 3000 K to 25000 K and pressure ranging from 50 kPa to 200 kPa, for optically thin and partially autoabsorbed plasmas. Finally, prototypal electrodes were studied and realized for a newly developed plasma source, based on the plasma needle concept and devoted to the generation of atmospheric pressure non-thermal plasmas for biomedical applications.

Structural verification of the ESEO spacecraft: from launch loads analysis to composite panels verification

The present thesis work was performed in the frame of ESEO (European Student Earth Orbiter) project. The activities that are described in this document were carried out in the Microsatellites and Space Micro systems Lab led by Professor Paolo Tortora and in ALMASpace company facilities. The thesis deals with ESEO structural analysis, at system and unit level, and verification: after determining the design limit loads to be applied to the spacecraft as an envelope of different launchers load profiles, a finite element structural analysis was performed on the model of the satellite in order to ensure the capability to withstand the loads encountered during the launch; all the analyses were performed according to ESA standards and using the software MSC NASTRAN SIMXPERT. Amplification factors were derived and used to determine loads to be considered at unit level. In particular structural analyses were carried out on the GPS unit, the payload developed for ESEO by students of University of Bologna and results were used in the preparation of GPS payload design definition file. As for the verification phase a study on the panels and inserts to be used in the spacecraft was performed: different designs were created exploiting methods to optimize weight and mechanical behavior. The configurations have been analyzed and results compared to select the final design.

Coating of surfaces of composite materials with enzymatically formed biosilica

Die Bildung kieselsäurehaltiger Spicula in marinen Schwämmen ist nur möglich durch die enzymatische Aktivität des Silicatein- in Verbindung mit der stöchiometrischen Selbstassemblierung des Enzyms mit anderen Schwammproteinen. Die vorliegende Arbeit basiert auf einem biomimetischen Ansatz mit dem Ziel, unterschiedliche Oberflächen für biotechnologische und biomedizinische Anwendungen mit Biosilica und Biotitania zu beschichten und zu funktionalisieren. Für biotechnologische Anwendungen ist dabei das Drucken von Cystein-getaggtem Silicatein auf Gold-Oberflächen von Bedeutung, denn es ermöglichte die Bildung definierter Biotitania-Strukturen (Anatas), welche als Photokatalysator den Abbau eines organischen Farbstoffs bewirkten. Des Weiteren zeigte sich die bio-inspirierte Modifikation von Tyrosin-Resten an rekombinantem Silicatein-(via Tyrosinase) als vielversprechendes Werkzeug zur Beschleunigung der Selbstassemblierung des Enzyms zu mesoskaligen Filamenten. Durch eine solche Modifikation konnte Silicatein auch auf der Oberfläche von anorganischen Partikeln immobilisiert werden, welches die Assemblierung von anorganisch-organischen Verbundwerkstoffen in wäßriger Umgebung förderte. Die resultierenden supramolekularen Strukturen könnten dabei in bio-inspirierten und biotechnologischen Anwendungen genutzt werden. Weiterhin wurde in der vorliegenden Arbeit die Sekundärstruktur von rekombinantem Silicatein- (Monomer und Oligomer) durch Raman Spektroskopie analysiert, nachdem das Protein gemäß einer neu etablierten Methode rückgefaltet worden war. Diese Spektraldaten zeigten insbesondere Änderungen der Proteinkonformation durch Solubilisierung und Oligomerisierung des Enzyms. Außerdem wurden die osteoinduzierenden und osteogenen Eigenschaften unterschiedlicher organischer Polymere, die herkömmlich als Knochenersatzmaterial genutzt werden, durch Oberflächenmodifikation mit Silicatein/Biosilica verbessert: Die bei der Kultivierung knochenbildender Zellen auf derart oberflächenbehandelten Materialien beobachtete verstärkte Biomineralisierung, Aktivierung der Alkalischen Phosphatase, und Ausbildung eines typischen zellulären Phänotyps verdeutlichen das Potential von Silicatein/Biosilica für der Herstellung neuartiger Implantat- und Knochenersatzmaterialien.

Sexual health of ethnic minority MSM in Britain (MESH project): design and methods

Background Men who have sex with men (MSM) remain the group most at risk of acquiring HIV infection in Britain. HIV prevalence appears to vary widely between MSM from different ethnic minority groups in this country for reasons that are not fully understood. The aim of the MESH project was to examine in detail the sexual health of ethnic minority MSM living in Britain. Methods/Design The main objectives of the MESH project were to explore among ethnic minority MSM living in Britain: (i) sexual risk behaviour and HIV prevalence; (ii) their experience of stigma and discrimination; (iii) disclosure of sexuality; (iv) use of, and satisfaction with sexual health services; (v) the extent to which sexual health services (for treatment and prevention) are aware of the needs of ethnic minority MSM. The research was conducted between 2006 and 2008 in four national samples: (i) ethnic minority MSM living in Britain; (ii) a comparison group of white British MSM living in Britain; (iii) NHS sexual health clinic staff in 15 British towns and cities with significant ethnic minority communities and; (iv) sexual health promotion/HIV prevention service providers. We also recruited men from two "key migrant" groups living in Britain: MSM born in Central or Eastern Europe and MSM born in Central or South America. Internet-based quantitative and qualitative research methods were used. Ethnic minority MSM were recruited through advertisements on websites, in community venues, via informal networks and in sexual health clinics. White and "key migrant" MSM were recruited mostly through Gaydar, one of the most popular dating sites used by gay men in Britain. MSM who agreed to take part completed a questionnaire online. Ethnic minority MSM who completed the online questionnaire were asked if they would be willing to take part in an online qualitative interview using email. Service providers were identified through the British Association of Sexual Health and HIV (BASHH) and the Terrence Higgins Trust (THT) CHAPS partnerships. Staff who agreed to take part were asked to complete a questionnaire online. The online survey was completed by 1241 ethnic minority MSM, 416 men born in South and Central America or Central and Eastern Europe, and 13,717 white British MSM; 67 ethnic minority MSM took part in the online qualitative interview. In addition 364 people working in sexual health clinics and 124 health promotion workers from around Britain completed an online questionnaire. Discussion The findings from this study will improve our understanding of the sexual health and needs of ethnic minority MSM in Britain.

Preventing vasospasm improves outcome after aneurysmal subarachnoid hemorrhage: rationale and design of CONSCIOUS-2 and CONSCIOUS-3 trials

Cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) is a frequent but unpredictable complication associated with poor outcome. Current vasospasm therapies are suboptimal; new therapies are needed. Clazosentan, an endothelin receptor antagonist, has shown promise in phase 2 studies, and two randomized, double-blind, placebo-controlled phase 3 trials (CONSCIOUS-2 and CONSCIOUS-3) are underway to further investigate its impact on vasospasm-related outcome after aSAH. Here, we describe the design of these studies, which was challenging with respect to defining endpoints and standardizing endpoint interpretation and patient care. Main inclusion criteria are: age 18-75 years; SAH due to ruptured saccular aneurysm secured by surgical clipping (CONSCIOUS-2) or endovascular coiling (CONSCIOUS-3); substantial subarachnoid clot; and World Federation of Neurosurgical Societies grades I-IV prior to aneurysm-securing procedure. In CONSCIOUS-2, patients are randomized 2:1 to clazosentan (5 mg/h) or placebo. In CONSCIOUS-3, patients are randomized 1:1:1 to clazosentan 5, 15 mg/h, or placebo. Treatment is initiated within 56 h of aSAH and continued until 14 days after aSAH. Primary endpoint is a composite of mortality and vasospasm-related morbidity within 6 weeks of aSAH (all-cause mortality, vasospasm-related new cerebral infarction, vasospasm-related delayed ischemic neurological deficit, neurological signs or symptoms in the presence of angiographic vasospasm leading to rescue therapy initiation). Main secondary endpoint is extended Glasgow Outcome Scale at week 12. A critical events committee assesses all data centrally to ensure consistency in interpretation, and patient management guidelines are used to standardize care. Results are expected at the end of 2010 and 2011 for CONSCIOUS-2 and CONSCIOUS-3, respectively.

Randomized clinical trial comparing percutaneous closure of patent foramen ovale (PFO) using the Amplatzer PFO Occluder with medical treatment in patients with cryptogenic embolism (PC-Trial): rationale and design

Background Several studies have shown an association of cryptogenic stroke and embolism with patent foramen ovale (PFO), but the question how to prevent further events in such patients is unresolved. Options include antithrombotic treatment with warfarin or antiplatelet agents or surgical or endovascular closure of the PFO. The PC-Trial was set up to compare endovascular closure and best medical treatment for prevention of recurrent events. Methods The PC-Trial is a randomized clinical trial comparing the efficacy of percutaneous closure of the PFO using the Amplatzer PFO occluder with best medical treatment in patients with cryptogenic embolism, i.e. mostly cryptogenic stroke. Warfarin for 6 months followed by antiplatelet agents is recommended as medical treatment. Randomization is stratified according to patients age (<45 versus ≥45 years), presence of atrial septal aneurysm (ASA yes or no) and number of embolic events before randomization (one versus more than one event). Primary endpoints are death, nonfatal stroke and peripheral embolism. Discussion patients were randomized in 29 centers of Europe, Canada, and Australia. Randomization started February 2000. Enrollment of 414 patients was completed in February 2009. All patients will be followed-up longitudinally. Follow-up is maintained until the last enrolled patient is beyond 2.5 years of follow-up (expected in 2011).

Hierarchical Approach for Survivable Network Design

A central design challenge facing network planners is how to select a cost-effective network configuration that can provide uninterrupted service despite edge failures. In this paper, we study the Survivable Network Design (SND) problem, a core model underlying the design of such resilient networks that incorporates complex cost and connectivity trade-offs. Given an undirected graph with specified edge costs and (integer) connectivity requirements between pairs of nodes, the SND problem seeks the minimum cost set of edges that interconnects each node pair with at least as many edge-disjoint paths as the connectivity requirement of the nodes. We develop a hierarchical approach for solving the problem that integrates ideas from decomposition, tabu search, randomization, and optimization. The approach decomposes the SND problem into two subproblems, Backbone design and Access design, and uses an iterative multi-stage method for solving the SND problem in a hierarchical fashion. Since both subproblems are NP-hard, we develop effective optimization-based tabu search strategies that balance intensification and diversification to identify near-optimal solutions. To initiate this method, we develop two heuristic procedures that can yield good starting points. We test the combined approach on large-scale SND instances, and empirically assess the quality of the solutions vis-à-vis optimal values or lower bounds. On average, our hierarchical solution approach generates solutions within 2.7% of optimality even for very large problems (that cannot be solved using exact methods), and our results demonstrate that the performance of the method is robust for a variety of problems with different size and connectivity characteristics.

Long-term consequences of an intensive care unit stay in older critically ill patients: design of a longitudinal study

Background Modern methods in intensive care medicine often enable the survival of older critically ill patients. The short-term outcomes for patients treated in intensive care units (ICUs), such as survival to hospital discharge, are well documented. However, relatively little is known about subsequent long-term outcomes. Pain, anxiety and agitation are important stress factors for many critically ill patients. There are very few studies concerned with pain, anxiety and agitation and the consequences in older critically ill patients. The overall aim of this study is to identify how an ICU stay influences an older person's experiences later in life. More specific, this study has the following objectives: (1) to explore the relationship between pain, anxiety and agitation during ICU stays and experiences of the same symptoms in later life; and (2) to explore the associations between pain, anxiety and agitation experienced during ICU stays and their effect on subsequent health-related quality of life, use of the health care system (readmissions, doctor visits, rehabilitation, medication use), living situation, and survival after discharge and at 6 and 12 months of follow-up. Methods/Design A prospective, longitudinal study will be used for this study. A total of 150 older critically ill patients in the ICU will participate (ICU group). Pain, anxiety, agitation, morbidity, mortality, use of the health care system, and health-related quality of life will be measured at 3 intervals after a baseline assessment. Baseline measurements will be taken 48 hours after ICU admission and one week thereafter. Follow-up measurements will take place 6 months and 12 months after discharge from the ICU. To be able to interpret trends in scores on outcome variables in the ICU group, a comparison group of 150 participants, matched by age and gender, recruited from the Swiss population, will be interviewed at the same intervals as the ICU group. Discussion Little research has focused on long term consequences after ICU admission in older critically ill patients. The present study is specifically focussing on long term consequences of stress factors experienced during ICU admission.

Learning from failure--rationale and design for a study about discontinuation of randomized trials (DISCO study)

Background Randomized controlled trials (RCTs) may be discontinued because of apparent harm, benefit, or futility. Other RCTs are discontinued early because of insufficient recruitment. Trial discontinuation has ethical implications, because participants consent on the premise of contributing to new medical knowledge, Research Ethics Committees (RECs) spend considerable effort reviewing study protocols, and limited resources for conducting research are wasted. Currently, little is known regarding the frequency and characteristics of discontinued RCTs. Methods/Design Our aims are, first, to determine the prevalence of RCT discontinuation for specific reasons; second, to determine whether the risk of RCT discontinuation for specific reasons differs between investigator- and industry-initiated RCTs; third, to identify risk factors for RCT discontinuation due to insufficient recruitment; fourth, to determine at what stage RCTs are discontinued; and fifth, to examine the publication history of discontinued RCTs. We are currently assembling a multicenter cohort of RCTs based on protocols approved between 2000 and 2002/3 by 6 RECs in Switzerland, Germany, and Canada. We are extracting data on RCT characteristics and planned recruitment for all included protocols. Completion and publication status is determined using information from correspondence between investigators and RECs, publications identified through literature searches, or by contacting the investigators. We will use multivariable regression models to identify risk factors for trial discontinuation due to insufficient recruitment. We aim to include over 1000 RCTs of which an anticipated 150 will have been discontinued due to insufficient recruitment. Discussion Our study will provide insights into the prevalence and characteristics of RCTs that were discontinued. Effective recruitment strategies and the anticipation of problems are key issues in the planning and evaluation of trials by investigators, Clinical Trial Units, RECs and funding agencies. Identification and modification of barriers to successful study completion at an early stage could help to reduce the risk of trial discontinuation, save limited resources, and enable RCTs to better meet their ethical requirements.

A Comparative Study of Central and Eastern European Social Policy Concernig Mental Disability

The main goal of this project was to identity whether an imported system of social policy can be suitable for a host country, and if not why not. Romanian social policy concerning the mentally disabled represents a paradoxical situation in that while social policy is designed to ensure both an institutional structure and a juridical environment, in practice it is far from successful. The central question which Ms. Ciumageanu asked therefore was whether this failure was due to systemic factors, or whether the problem lay in reworking an imported social policy system to meet local needs. She took a comparative approach, also considering both the Scandinavian model of social policy, particularly the Danish model which has been adopted in Romania, and the Hungarian system, which has inherited a similar universal welfare system and perpetuated it to some extent. In order to verify her hypothesis, she also studied the transformation of the welfare system in Great Britain, which meant a shift from state responsibility towards community care. In all these she concentrated on two major aspects: the structural design within the different countries and, at a micro level, the societal response. Following her analyses of the various in the other countries concerned, Ms. Ciumageanu concluded that the major differences lie first in the difference between the stages of policy design. Here Denmark is the most advanced and Romania the most backwards. Denmark has a fairly elaborate infrastructure, Britain a system with may gaps to bridge, and Hungary and Romania are struggling with severe difficulties owing both to the inherited structure and the limits imposed by an inadequate GDP. While in Denmark and Britain, mental patients are integrated into an elaborate system of care, designed and administered by the state (in Denmark) or communities (in Britain), in Hungary and Romania, the state designs and fails to implement the policy and community support is minimal, partly due to the lack of a fully developed civil society. At the micro level the differences are similar. While in Denmark and Britain there is a consensus about the roles of the state and of civil societies (although at different levels in the two countries, with the state being more supportive in Denmark), in Romania and to a considerable extent in Hungary, civil society tends to expect too much from the state, which in its turn is withdrawing faster from its social roles than from its economic ones, generating a gap between the welfare state and the market economy and disadvantaging the expected transition from a welfare state to a welfare society and, implicitly, the societal response towards those mentally disabled persons in it. On an intermediate level, the factors influencing social policy as a whole were much the same for Hungary and Romania. Economic factors include the accumulated economic resources of both state and citizens, and the inherited pattern of redistribution, as well as the infrastructure; institutional resources include the role of the state and the efficiency of the state bureaucracy, the strength and efficiency of the state apparatus, political stability and the complexity of political democratisation, the introduction of market institutions, the strength of civil society and civic sector institutions. From the standpoint of the societal response, some factors were common to all countries, particularly the historical context, the collective and institutional memories and established patterns of behaviour. In the specific case of Romania, general structural and environmental factors - industrialisation and forced urbanisation - have had a definite influence on family structure, values and behavioural patterns. The analysis of Romanian social policy revealed several causes for failure to date. The first was the instability of the policy and the failure to consider the structural network involved in developing it, rather than just the results obtained. The second was the failure to take into account the relationship between the individual and the group in all its aspects, followed by the lack of active assistance for prevention, re-socialisation or professional integration of persons with mental disabilities. Finally, the state fails to recognise its inability to support an expensive psychiatric enterprise and does not provide any incentive to the private sector. This creates tremendous social costs for both the state and the individual. NGOs working in the field in Romania have been somewhat more successful but are still limited by their lack of funding and personnel and the idea of a combined system is as yet utopian in the circumstances in the country.

Monument Preservation in Central Europe

Recent decades have seen both what has been referred to as an "inflation of historical monuments" and an acceleration of the process of "monumentification" affecting buildings of relatively recent date. In order to gain a better understanding of this, Kovacs looked at the experience in countries of Central Europe (Romania, Hungary, Slovenia, the Czech Lands, Slovakia), discovering a number of similarities as well as differences in detail. More important, however, was the discovery of the much wider importance of this phenomenon as a whole, which is particularly visible in this part of Europe, where "European" theory and practice of monument preservation are combined with progressivist demolitionism and traditional "natural" attitudes towards the built environment. Kovacs found that monument preservation has not only become a major occupation within building activity seen as a matter of anthropology, but also seems to be the determining feature of the contemporary cultural attitude. The scale of preservation activity has long since reached the level of urban design as an essential criterion for matters of future development, making it necessary to extend the conclusions of theoretical research down to broader generalities of the building domain. Kovacs then looked at the specific features of the countries concerned, including the survival of traditional building techniques in Romania, and the wide variety of preservationist policies in use.

Determination of caries risk at resin composite margins

PURPOSE: To design an artificial mouth in order to evaluate if a new diagnostic tool (Clinpro Cario Diagnosis) can be used for early detection of secondary caries at resin composite margins in vitro. METHODS: 32 intact human third molars received standardized Class-V resin composite restorations (Tetric Ceram bonded with Syntac SC). After storage for 4 weeks at 37 degrees C, teeth were subjected to 5,000 or 10,000 thermocycles (+/- 5 degrees C and +/- 55 degrees C) and polysiloxane impressions were taken. Streptococcus mutans 10449 (SM) was used in a nutrition medium to initiate a secondary caries process. Daily, the teeth were incubated for 2 x 2.5 hours in SM containing nutrition medium followed by 2 x 9.5 hours incubation in artificial saliva. Teeth were investigated after total incubation periods of 4, 6, and 8 weeks. After the different incubation protocols, the restoration margins were evaluated for infection and secondary caries processes in using Clinpro Cario Diagnosis which measures site-specifically the lactic acid production of SM in response to a sucrose challenge. The color signal was read 5 minutes after removal of the diagnostic impression. After thermocycling and biological load cycling, precision polysiloxane impressions were taken and replicas were investigated under a light microscope for gap widths at enamel and dentin margins. Demineralization was evaluated by fluorescence microscopy in using a special FITC filter. The demineralization depths at the cavity margin were calculated with Xpert for Windows using a pixel distance of 5 microm. RESULTS: After the different thermocycling protocols, no differences in gap widths and demineralization depths were found (P > 0.05). After SM incubation, gap widths and demineralization depths were significantly dependent on SM incubation time and previous number of thermocycles (P < 0.05). Lactic acid formations of SM were detectable by Clinpro Cario Diagnosis at dentin cavosurface margins formed after 6 weeks of incubation with SM (P < 0.05).

Corrugated wood composite panels for structural decking

High flexural strength and stiffness can be achieved by forming a thin panel into a wave shape perpendicular to the bending direction. The use of corrugated shapes to gain flexural strength and stiffness is common in metal and reinforced plastic products. However, there is no commercial production of corrugated wood composite panels. This research focuses on the application of corrugated shapes to wood strand composite panels. Beam theory, classical plate theory and finite element models were used to analyze the bending behavior of corrugated panels. The most promising shallow corrugated panel configuration was identified based on structural performance and compatibility with construction practices. The corrugation profile selected has a wavelength equal to 8”, a channel depth equal to ¾”, a sidewall angle equal to 45 degrees and a panel thickness equal to 3/8”. 16”x16” panels were produced using random mats and 3-layer aligned mats with surface flakes parallel to the channels. Strong axis and weak axis bending tests were conducted. The test results indicate that flake orientation has little effect on the strong axis bending stiffness. The 3/8” thick random mat corrugated panels exhibit bending stiffness (400,000 lbs-in2/ft) and bending strength (3,000 in-lbs/ft) higher than 23/32” or 3/4” thick APA Rated Sturd-I-Floor with a 24” o.c. span rating. Shear and bearing test results show that the corrugated panel can withstand more than 50 psf of uniform load at 48” joist spacings. Molding trials on 16”x16” panels provided data for full size panel production. Full size 4’x8’ shallow corrugated panels were produced with only minor changes to the current oriented strandboard manufacturing process. Panel testing was done to simulate floor loading during construction, without a top underlayment layer, and during occupancy, with an underlayment over the panel to form a composite deck. Flexural tests were performed in single-span and two-span bending with line loads applied at mid-span. The average strong axis bending stiffness and bending strength of the full size corrugated panels (without the underlayment) were over 400,000 lbs-in2/ft and 3,000 in-lbs/ft, respectively. The composite deck system, which consisted of an OSB sheathing (15/32” thick) nailed-glued (using 3d ringshank nails and AFG-01 subfloor adhesive) to the corrugated subfloor achieved about 60% of the full composite stiffness resulting in about 3 times the bending stiffness of the corrugated subfloor (1,250,000 lbs-in2/ft). Based on the LRFD design criteria, the corrugated composite floor system can carry 40 psf of unfactored uniform loads, limited by the L/480 deflection limit state, at 48” joist spacings. Four 10-ft long composite T-beam specimens were built and tested for the composite action and the load sharing between a 24” wide corrugated deck system and the supporting I-joist. The average bending stiffness of the composite T-beam was 1.6 times higher than the bending stiffness of the I-joist. A 8-ft x 12-ft mock up floor was built to evaluate construction procedures. The assembly of the composite floor system is relatively simple. The corrugated composite floor system might be able to offset the cheaper labor costs of the single-layer Sturd-IFloor through the material savings. However, no conclusive result can be drawn, in terms of the construction costs, at this point without an in depth cost analysis of the two systems. The shallow corrugated composite floor system might be a potential alternative to the Sturd-I-Floor in the near future because of the excellent flexural stiffness provided.

The blood-central nervous system barriers actively control immune cell entry into the central nervous system

Before entering the central nervous system (CNS) immune cells have to penetrate any one of its barriers, namely either the endothelial blood-brain barrier, the epithelial blood-cerebrospinal fluid barrier or the tanycytic barrier around the circumventricular organs, all of which maintain homeostasis within the CNS. The presence of these barriers in combination with the lack of lymphatic vessels and the absence of classical MHC-positive antigen presenting cells characterizes the CNS as an immunologically privileged site. In multiple sclerosis a large number of inflammatory cells gains access to the CNS parenchyma. Studies performed in experimental autoimmune encephalomyelitis (EAE), a rodent model for multiple sclerosis, have enabled us to understand some of the molecular mechanisms involved in immune cell entry into the CNS. In particular, the realization that /alpha4-integrins play a predominant role in leukocyte trafficking to the CNS has led to the development of a novel drug for the treatment of relapsing-remitting multiple sclerosis, which targets /alpha4-integrin mediated immune cell migration to the CNS. At the same time, the involvement of other adhesion and signalling molecules in this process remains to be investigated and novel molecules contributing to immune cell entry into the CNS are still being identified. The entire process of immune cell trafficking into the CNS is strictly controlled by the brain barriers not only under physiological conditions but also during neuroinflammation, when some barrier properties are lost. Thus, immune cell entry into the CNS critically depends on the unique characteristics of the brain barriers maintaining CNS homeostasis.

Strategic Emergency department design: An approach to capacity planning in healthcare provision in overcrowded emergency rooms

Healthcare professionals and the public have increasing concerns about the ability of emergency departments to meet current demands. Increased demand for emergency services, mainly caused by a growing number of minor and moderate injuries has reached crisis proportions, especially in the United Kingdom. Numerous efforts have been made to explore the complex causes because it is becoming more and more important to provide adequate healthcare within tight budgets. Optimisation of patient pathways in the emergency department is therefore an important factor. This paper explores the possibilities offered by dynamic simulation tools to improve patient pathways using the emergency department of a busy university teaching hospital in Switzerland as an example.