Finite element methods for the Stokes system based on a Zienkiewicz type N-simplex

Hermite interpolation is increasingly showing to be a powerful numerical solution tool, as applied to different kinds of second order boundary value problems. In this work we present two Hermite finite element methods to solve viscous incompressible flows problems, in both two- and three-dimension space. In the two-dimensional case we use the Zienkiewicz triangle to represent the velocity field, and in the three-dimensional case an extension of this element to tetrahedra, still called a Zienkiewicz element. Taking as a model the Stokes system, the pressure is approximated with continuous functions, either piecewise linear or piecewise quadratic, according to the version of the Zienkiewicz element in use, that is, with either incomplete or complete cubics. The methods employ both the standard Galerkin or the Petrov–Galerkin formulation first proposed in Hughes et al. (1986) [18], based on the addition of a balance of force term. A priori error analyses point to optimal convergence rates for the PG approach, and for the Galerkin formulation too, at least in some particular cases. From the point of view of both accuracy and the global number of degrees of freedom, the new methods are shown to have a favorable cost-benefit ratio, as compared to velocity Lagrange finite elements of the same order, especially if the Galerkin approach is employed.

The Emergence of the Post-Socialist Welfare State - The Case of the Baltic States : Estonia, Latvia and Lithuania

This dissertation takes a step towards providing a better understanding of post-socialist welfare state development from a theoretical as well as an empirical perspective. The overall analytical goal of this thesis has been to critically assess the development of social policies in Estonia, Latvia and Lithuania using them as illustrative examples of post-socialist welfare state development in the light of the theories, approaches and typologies that have been developed to study affluent capitalist democracies. The four studies included in this dissertation aspire to a common aim in a number of specific ways. The first study tries to place the ideal-typical welfare state models of the Baltic States within the well-known welfare state typologies. At the same time, it provides a rich overview of the main social security institutions in the three countries by comparing them with each other and with the previous structures of the Soviet period. It examines the social insurance institutions of the Baltic States (old-age pensions, unemployment insurance, short-term benefits, sickness, maternity and parental insurance and family benefits) with respect to conditions of eligibility, replacement rates, financing and contributions. The findings of this study indicate that the Latvian social security system can generally be labelled as a mix of the basic security and corporatist models. The Estonian social security system can generally also be characterised as a mix of the basic security and corporatist models, even if there are some weak elements of the targeted model in it. It appears that the institutional changes developing in the social security system of Lithuania have led to a combination of the basic security and targeted models of the welfare state. Nevertheless, as the example of the three Baltic States shows, there is diversity in how these countries solve problems within the field of social policy. In studying the social security schemes in detail, some common features were found that could be attributed to all three countries. Therefore, the critical analysis of the main social security institutions of the Baltic States in this study gave strong supporting evidence in favour of identifying the post-socialist regime type that is already gaining acceptance within comparative welfare state research. Study Two compares the system of social maintenance and insurance in the Soviet Union, which was in force in the three Baltic countries before their independence, with the currently existing social security systems. The aim of the essay is to highlight the forces that have influenced the transformation of the social policy from its former highly universal, albeit authoritarian, form, to the less universal, social insurance-based systems of present-day Estonia, Latvia and Lithuania. This study demonstrates that the welfare–economy nexus is not the only important factor in the development of social programs. The results of this analysis revealed that people's attitudes towards distributive justice and the developmental level of civil society also play an important part in shaping social policies. The shift to individualism in people’s mentality and the decline of the labour movement, or, to be more precise, the decline in trade union membership and influence, does nothing to promote the development of social rights in the Baltic countries and hinders the expansion of social policies. The legacy of the past has been another important factor in shaping social programs. It can be concluded that social policy should be studied as if embedded not only in the welfare-economy nexus, but also in the societal, historical and cultural nexus of a given society. Study Three discusses the views of the state elites on family policy within a wider theoretical setting covering family policy and social policy in a broader sense and attempts to expand this analytical framework to include other post-socialist countries. The aim of this essay is to explore the various views of the state elites in the Baltics concerning family policy and, in particular, family benefits as one of the possible explanations for the observed policy differences. The qualitative analyses indicate that the Baltic States differ significantly with regard to the motives behind their family policies. Lithuanian decision-makers seek to reduce poverty among families with children and enhance the parents’ responsibility for bringing up their children. Latvian policy-makers act so as to increase the birth rate and create equal opportunities for children from all families. Estonian policy-makers seek to create equal opportunities for all children and the desire to enhance gender equality is more visible in the case of Estonia in comparison with the other two countries. It is strongly arguable that there is a link between the underlying motives and the kinds of family benefits in a given country. This study, thus, indicates how intimately the attitudes of the state bureaucrats, policy-makers, political elite and researchers shape social policy. It confirms that family policy is a product of the prevailing ideology within a country, while the potential influence of globalisation and Europeanisation is detectable too. The final essay takes into account the opinions of welfare users and examines the performances of the institutionalised family benefits by relying on the recipients’ opinions regarding these benefits. The opinions of the populations as a whole regarding government efforts to help families are compared with those of the welfare users. Various family benefits are evaluated according to the recipients' satisfaction with those benefits as well as the contemporaneous levels of subjective satisfaction with the welfare programs related to the absolute level of expenditure on each program. The findings of this paper indicate that, in Latvia, people experience a lower level of success regarding state-run family insurance institutions, as compared to those in Lithuania and Estonia. This is deemed to be because the cash benefits for families and children in Latvia are, on average, seen as marginally influencing the overall financial situation of the families concerned. In Lithuania and Estonia, the overwhelming majority think that the family benefit systems improve the financial situation of families. It appears that recipients evaluated universal family benefits as less positive than targeted benefits. Some universal benefits negatively influenced the level of general satisfaction with the family benefits system provided in the countries being researched. This study puts forward a discussion about whether universalism is always more legitimate than targeting. In transitional economies, in which resources are highly constrained, some forms of universal benefits could turn out to be very expensive in relative terms, without being seen as useful or legitimate forms of help to families. In sum, by closely examining the different aspects of social policy, this dissertation goes beyond the over-generalisation of Eastern European welfare state development and, instead, takes a more detailed look at what is really going on in these countries through the examples of Lithuania, Latvia and Estonia. In addition, another important contribution made by this study is that it revives ‘western’ theoretical knowledge through ‘eastern’ empirical evidence and provides the opportunity to expand the theoretical framework for post-socialist societies.

The immunogenicity of chemically derived zwitterionic polysaccharides

Bacterial capsular polysaccharides (PS) which naturally contain zwitterionic charge motifs (ZPS) possess specific immunostimulatory activity, leading to direct activation of antigen-presenting cells (APCs) through Toll-like receptor 2 (TLR2) and of T cells in co-culture systems. When administered intraperitoneally, ZPS and bacteria expressing them are involved in the induction or regulation of T-cell dependent inflammatory processes such as intra-abdominal abscess formation. Moreover it has been published that ZPSs are processed to low molecular weight carbohydrates and presented to T cells through a pathway similar to that used for protein antigens. These findings were in contrast with the paradigm according to which polysaccharides are T-independent antigens unable to be presented in association with MHC class II molecules and unable to induce a protective immune response. For this reason in glycoconjugate vaccines polysaccharides often need to be conjugated to a carrier protein to induce protection. The aim of our work was to generate vaccine candidates with antigen and adjuvant properties in one molecule by the chemical introduction of a positive charge into naturally anionic PS from group B streptococcus (GBS). The resulting zwitterionic PS (ZPS) has the ability to activate human and mouse APCs, and in mixed co-cultures of monocytes and T cells, ZPS induce MHC II-dependent T-cell proliferation and up-regulation of activation markers. TLR2 transfectants show reporter gene transcription upon incubation with ZPS and these stimulatory qualities can be blocked by anti-TLR2 mAbs or by the destruction of the zwitterionic motif. However, in vivo, ZPS used alone as vaccine antigen failed to induce protection against GBS challenge, a result which does not confirm the above mentioned postulate that ZPS are T-cell dependent Ags by virtue of their charge motif. Thus to make ZPS visible to the immune system we have conjugated ZPS with a carrier protein. ZPS-glycoconjugates induce higher T cell and Ab responses to carrier and PS, respectively, compared to control PS-glycoconjugates made with the native polysaccharide form. Moreover, protection of mothers or neonate offspring from lethal GBS challenge is better when mothers are immunized with ZPS-conjugates compared to immunization with PS-conjugates. In TLR2 knockout mice, ZPS-conjugates lose both their increased immunogenicity and protective effect after vaccination. When ZPS are co-administered as adjuvants with unconjugated tetanus toxoid (TT), they have the ability to increase the TT-specific antibody titer. In conclusion, glycoconjugates containing ZPS are potent vaccines. They target Ag to TLR2-expressing APCs and activate these APCs, leading to better T cell priming and ultimately to higher protective Ab titers. Thus, rational chemical design can generate potent novel PS-adjuvants with wide application, including glycoconjugates and co-administration with unrelated protein Ags.

Structure and dynamics of supramolecular assemblies studied by advanced solid-state NMR spectroscopy

Ziel der vorliegenden Arbeit ist die Aufklärung von Struktur und Dynamik komplexer supramolekularer Systeme mittels Festkörper NMR Spektroskopie. Die Untersuchung von pi-pi Wechselwirkungen, welche einen entscheidenden Einfluss auf die strukturellen und dynamischen Eigenschaften supra- molekularer Systeme haben, hilft dabei, die Selbst- organisationsprozesse dieser komplexen Materialien besser zu verstehen. Mit dipolaren 1H-1H and 1H-13C Wiedereinkopplungs NMR Methoden unter schnellem MAS können sowohl 1H chemische Verschiebungen als auch dipolare 1H-1H und 1H-13C Kopplungen untersucht werden, ohne dass eine Isotopenmarkierung erforderlich ist. So erhält man detaillierte Informationen über die Struktur und die Beweglichkeit einzelner Molekül- segmente. In Verbindung mit sogenannten nucleus independent chemical shift (NICS) maps (berechnet mit ab-initio Methoden) lassen sich Abstände von Protonen relativ zu pi-Elektronensystemen bestimmen und so Strukturvorschläge ableiten. Mit Hilfe von homo- und heteronuklearen dipolaren Rotationsseitenbandenmustern könnenaußerdem Ordnungs- parameter für verschiedene Molekülsegmente bestimmt werden. Die auf diese Weise gewonnenen Informationen über die strukturellen und dynamischen Eigenschaften supramolekularer Systeme tragen dazu bei, strukturbestimmende Molekül- einheiten und Hauptordnungsphänomene zu identifizieren sowie lokale Wechselwirkungen zu quantifizieren, um so den Vorgang der Selbstorganisation besser zu verstehen.

Patient-Therapeut-Bindung bei Drogenabhängigen: Instrumentenvalidierung und Therapieevaluation

In der vorliegenden Arbeit wird zum einen ein Instrument zur Erfassung der Patient-Therapeut-Bindung validiert (Client Attachment to Therapist Scale, CATS; Mallinckrodt, Coble & Gantt, 1995), zum anderen werden Hypothesen zu den Zusammenhängen zwischen Selbstwirksamkeitserwartung, allgemeinem Bindungsstil, therapeutischer Beziehung (bzw. Therapiezufriedenheit), Patient-Therapeut-Bindung und Therapieerfolg bei Drogen-abhängigen in stationärer Postakutbehandlung überprüft. In die Instrumentenvalidierung (einwöchiger Retest) wurden 119 Patienten aus 2 Kliniken und 13 Experten einbezogen. Die Gütekriterien des Instrumentes fallen sehr zufriedenstellend aus. An der naturalistischen Therapieevaluationsstudie (Prä-, Prozess-, Post-Messung: T0, T1, T2) nahmen 365 Patienten und 27 Therapeuten aus 4 Kliniken teil. Insgesamt beendeten 44,1% der Patienten ihren stationären Aufenthalt planmäßig. Auf Patientenseite erweisen sich Alter und Hauptdiagnose, auf Therapeutenseite die praktizierte Therapierichtung als Therapieerfolgsprädiktoren. Selbstwirksamkeitserwartung, allgemeiner Bindungsstil, Patient-Therapeut-Bindung und Therapiezufriedenheit eignen sich nicht zur Prognose des Therapieerfolgs. Die zu T0 stark unterdurchschnittlich ausgeprägte Selbstwirksamkeits-erwartung steigert sich über den Interventionszeitraum, wobei sich ein Moderatoreffekt der Patient-Therapeut-Bindung beobachten lässt. Es liegt eine hohe Prävalenz unsicherer allgemeiner Bindungsstile vor, welche sich über den Therapiezeitraum nicht verändern. Die patientenseitige Zufriedenheit mit der Therapie steigt von T1 zu T2 an. Die Interrater-Konkordanz (Patient/Therapeut) zur Einschätzung der Patient-Therapeut-Bindung erhöht sich leicht von T1 zu T2. Im Gegensatz dazu wird die Therapiezufriedenheit von Patienten und Therapeuten zu beiden Messzeitpunkten sehr unterschiedlich beurteilt. Die guten Testgütekriterien der CATS sprechen für eine Überlegenheit dieses Instrumentes gegenüber der Skala zur Erfassung der Therapiezufriedenheit. Deshalb sollte die Patient-Therapeut-Bindung anhand dieses Instrumentes in weiteren Forschungsarbeiten an anderen Patientenkollektiven untersucht werden, um generalisierbare Aussagen zur Validität treffen zu können.

Brain-Computer Interfaces for augmented communication: Asynchronous and adaptive algorithms and evaluation with end users

This thesis aimed at addressing some of the issues that, at the state of the art, avoid the P300-based brain computer interface (BCI) systems to move from research laboratories to end users’ home. An innovative asynchronous classifier has been defined and validated. It relies on the introduction of a set of thresholds in the classifier, and such thresholds have been assessed considering the distributions of score values relating to target, non-target stimuli and epochs of voluntary no-control. With the asynchronous classifier, a P300-based BCI system can adapt its speed to the current state of the user and can automatically suspend the control when the user diverts his attention from the stimulation interface. Since EEG signals are non-stationary and show inherent variability, in order to make long-term use of BCI possible, it is important to track changes in ongoing EEG activity and to adapt BCI model parameters accordingly. To this aim, the asynchronous classifier has been subsequently improved by introducing a self-calibration algorithm for the continuous and unsupervised recalibration of the subjective control parameters. Finally an index for the online monitoring of the EEG quality has been defined and validated in order to detect potential problems and system failures. This thesis ends with the description of a translational work involving end users (people with amyotrophic lateral sclerosis-ALS). Focusing on the concepts of the user centered design approach, the phases relating to the design, the development and the validation of an innovative assistive device have been described. The proposed assistive technology (AT) has been specifically designed to meet the needs of people with ALS during the different phases of the disease (i.e. the degree of motor abilities impairment). Indeed, the AT can be accessed with several input devices either conventional (mouse, touchscreen) or alterative (switches, headtracker) up to a P300-based BCI.

Automatic induction of lexical features

This thesis concerns artificially intelligent natural language processing systems that are capable of learning the properties of lexical items (properties like verbal valency or inflectional class membership) autonomously while they are fulfilling their tasks for which they have been deployed in the first place. Many of these tasks require a deep analysis of language input, which can be characterized as a mapping of utterances in a given input C to a set S of linguistically motivated structures with the help of linguistic information encoded in a grammar G and a lexicon L: G + L + C → S (1) The idea that underlies intelligent lexical acquisition systems is to modify this schematic formula in such a way that the system is able to exploit the information encoded in S to create a new, improved version of the lexicon: G + L + S → L' (2) Moreover, the thesis claims that a system can only be considered intelligent if it does not just make maximum usage of the learning opportunities in C, but if it is also able to revise falsely acquired lexical knowledge. So, one of the central elements in this work is the formulation of a couple of criteria for intelligent lexical acquisition systems subsumed under one paradigm: the Learn-Alpha design rule. The thesis describes the design and quality of a prototype for such a system, whose acquisition components have been developed from scratch and built on top of one of the state-of-the-art Head-driven Phrase Structure Grammar (HPSG) processing systems. The quality of this prototype is investigated in a series of experiments, in which the system is fed with extracts of a large English corpus. While the idea of using machine-readable language input to automatically acquire lexical knowledge is not new, we are not aware of a system that fulfills Learn-Alpha and is able to deal with large corpora. To instance four major challenges of constructing such a system, it should be mentioned that a) the high number of possible structural descriptions caused by highly underspeci ed lexical entries demands for a parser with a very effective ambiguity management system, b) the automatic construction of concise lexical entries out of a bulk of observed lexical facts requires a special technique of data alignment, c) the reliability of these entries depends on the system's decision on whether it has seen 'enough' input and d) general properties of language might render some lexical features indeterminable if the system tries to acquire them with a too high precision. The cornerstone of this dissertation is the motivation and development of a general theory of automatic lexical acquisition that is applicable to every language and independent of any particular theory of grammar or lexicon. This work is divided into five chapters. The introductory chapter first contrasts three different and mutually incompatible approaches to (artificial) lexical acquisition: cue-based queries, head-lexicalized probabilistic context free grammars and learning by unification. Then the postulation of the Learn-Alpha design rule is presented. The second chapter outlines the theory that underlies Learn-Alpha and exposes all the related notions and concepts required for a proper understanding of artificial lexical acquisition. Chapter 3 develops the prototyped acquisition method, called ANALYZE-LEARN-REDUCE, a framework which implements Learn-Alpha. The fourth chapter presents the design and results of a bootstrapping experiment conducted on this prototype: lexeme detection, learning of verbal valency, categorization into nominal count/mass classes, selection of prepositions and sentential complements, among others. The thesis concludes with a review of the conclusions and motivation for further improvements as well as proposals for future research on the automatic induction of lexical features.

Operational research applied to regional healthcare system

In this thesis we focus on optimization and simulation techniques applied to solve strategic, tactical and operational problems rising in the healthcare sector. At first we present three applications to Emilia-Romagna Public Health System (SSR) developed in collaboration with Agenzia Sanitaria e Sociale dell'Emilia-Romagna (ASSR), a regional center for innovation and improvement in health. Agenzia launched a strategic campaign aimed at introducing Operations Research techniques as decision making tools to support technological and organizational innovations. The three applications focus on forecast and fund allocation of medical specialty positions, breast screening program extension and operating theater planning. The case studies exploit the potential of combinatorial optimization, discrete event simulation and system dynamics techniques to solve resource constrained problem arising within Emilia-Romagna territory. We then present an application in collaboration with Dipartimento di Epidemiologia del Lazio that focuses on population demand of service allocation to regional emergency departments. Finally, a simulation-optimization approach, developed in collaboration with INESC TECH center of Porto, to evaluate matching policies for the kidney exchange problem is discussed.

Einstellungen zur Demokratie in Kambodscha : Niveau und Determinanten der Demokratieunterstützung

Die vorliegende Arbeit beschäftigt sich mit der Frage, wie stark die Unterstützung eines demokratischen politischen Systems in der kambodschanischen Bevölkerung ist und welche Faktoren auf der Mikroebene die Demokratieunterstützung in Kambodscha beeinflussen. Hierfür werden das Unterstützungsmodell von Dieter Fuchs und die Modernisierungstheorie von Seymour Lipset für die Analyse von Einstellungen in einem autoritären politischen System modifiziert und entsprechend angepasste Hypothesen [zum Einfluss der Modernisierungsfaktoren auf die Demokratieunterstützung] formuliert. Nachdem die im Datensatz vorhandenen Einzelindikatoren zu Faktoren verdichtet und Probleme des Demokratieverständnisses und der Item-Nonresponse diskutiert wurden, werden Daten der zweiten Welle der Asian Barometer Survey 2008 analysiert. Die empirischen Ergebnisse zeigen zwar, dass eine substantielle Minderheit das autoritäre Regime des Landes und seine Entscheidungsträger kritisch betrachtet, die Bindung an liberal-demokratische Werte aber eher schwach ausgeprägt ist. Bi- und multivariate Analysen deuten auf einen Einfluss von Faktoren wie Bildung, Einkommen und Wohnort hin und bestätigen somit weitgehend die Modernisierungstheorie, allerdings mit einer bedeutsamen Abweichung: Größere Zufriedenheit mit der eigenen wirtschaftlichen Lage führt zwar zu einer stärkeren Bindung an demokratische Werte, gleichzeitig aber auch zu einer größeren Unterstützung des autoritären Regimes und seiner Entscheidungsträger.

Na +-coupled betaine symporters involved in osmotic stress response in prokaryotes and eukaryotes

The betaine/GABA transporter BGT1 is one of the most important osmolyte transporters in the kidney. BGT1 is a member of the neurotransmitter sodium symporter (NSS) family, facilitates Na+/Cl--coupled betaine uptake to cope with hyperosmotic stress. Betaine transport in kidney cells is upregulated under hypertonic conditions by a yet unknown mechanism when increasing amounts of intracellular BGT1 are inserted into the plasma membrane. Re-establishing isotonicity results in ensuing depletion of BGT1 from the membrane. BGT1 phosphorylation on serines and threonines might be a regulation mechanism. In the present study, four potential PKC phosphorylation sites were mutated to alanines and the responses to PKC activators, phorbol 12-myristate acetate (PMA) and dioctanoyl-sn-glycerol (DOG) were determined. GABA-sensitive currents were diminished after 30 min preincubation with these PKC activators. Staurosporine blocked the response to DOG. Three mutants evoked normal GABA-sensitive currents but currents in oocytes expressing the mutant T40A were greatly diminished. [3H]GABA uptake was also determined in HEK-293 cells expressing EGFP-tagged BGT1 with the same mutations. Three mutants showed normal upregulation of GABA uptake after hypertonic stress, and downregulation by PMA was normal compared to EGFP-BGT1. In contrast, GABA uptake by the T40A mutant showed no response to hypertonicity or PMA. Confocal microscopy of the EGFP-BGT1 mutants expressed in MDCK cells, grown on glass or filters, revealed that T40A was present in the cytoplasm after 24 h hypertonic stress while the other mutants and EGFP-BGT1 were predominantely present in the plasma membrane. All four mutants co-migrated with EGFP-BGT1 on Western blots suggesting they are full-length proteins. In conclusion, T235, S428, and S564 are not involved in downregulation of BGT1 due to phosphorylation by PKC. However, T40 near the N-terminus may be part of a hot spot important for normal trafficking or insertion of BGT1 into the plasma membrane. Additionally, a link between substrate transport regulation, insertion of BGT1 into the plasma membrane and N-glycosylation in the extracellular loop 2 (EL2) could be revealed. The functional importance of two predicted N-glycosylation sites, which are conserved in EL2 within the NSS family were investigated for trafficking, transport and regulated plasma membrane insertion by immunogold-labelling, electron microscopy, mutagenesis, two-electrode voltage clamp measurements in Xenopus laevis oocytes and uptake of radioactive-labelled substrate into MDCK cells. Trafficking and plasma membrane insertion of BGT1 was clearly promoted by proper N-glycosylation in both, oocytes and MDCK cells. De-glycosylation with PNGase F or tunicamycin led to a decrease in substrate affinity and transport rate. Mutagenesis studies revealed that in BGT1 N183 is the major N-glycosylation site responsible for full protein activity. Replacement of N183 with aspartate resulted in a mutant, which was not able to bind N-glycans suggesting that N171 is a non-glycosylated site in BGT1. N183D exhibited close to WT transport properties in oocytes. Surprisingly, in MDCK cells plasma membrane insertion of the N183D mutant was no longer regulated by osmotic stress indicating unambiguously that association with N-glycans at this position is linked to osmotic stress-induced transport regulation in BGT1. The molecular transport mechanism of BGT1 remains largely unknown in the absence of a crystal structure. Therefore investigating the structure-function relationship of BGT1 by a combination of structural biology (2D and 3D crystallization) and membrane protein biochemistry (cell culture, substrate transport by radioactive labeled GABA uptake into cells and proteoliposomes) was the aim of this work. While the functional assays are well established, structure determination of eukaryotic membrane transporters is still a challenge. Therefore, a suitable heterologous expression system could be defined, starting with cloning and overexpression of an optimized gene. The achieved expression levels in P. pastoris were high enough to proceed with isolation of BGT1. Furthermore, purification protocols could be established and resulted in pure protein, which could even be reconstituted in an active form. The quality and homogeneity of the protein allowed already 2D and 3D crystallization, in which initial crystals could be obtained. Interestingly, the striking structural similarity of BGT1 to the bacterial betaine transporter BetP, which became a paradigm for osmoregulated betaine transport, provided information on substrate coordination in BGT1. The structure of a BetP mutant that showed activity for GABA was solved to 3.2Å in complex with GABA in an inward facing open state. This structure shed some light into the molecular transport mechanisms in BGT1 and might help in future to design conformationally locked BGT1 to enforce the on-going structure determination.

Anti insulin-like growth factor I receptor immunoliposomes: a single formulation combining two anticancer treatments with enhanced therapeutic efficiency

Context: Through overexpression and aberrant activation in many human tumors, the IGF system plays a key role in tumor development and tumor cell proliferation. Different strategies targeting IGF-I receptor (IGFI-R) have been developed, and recent studies demonstrated that combined treatments with cytostatic drugs enhance the potency of anti-IGFI-R therapies. Objective: The objective of the study was to examine the IGFI-R expression status in neuroendocrine tumors of the gastroenteropancreatic system (GEP-NETs) in comparison with healthy tissues and use potential overexpression as a target for novel anti-IGFI-R immunoliposomes. Experimental Design: A human tumor tissue array and samples from different normal tissues were investigated by immunohistochemistry. An IGFI-R antagonistic antibody (1H7) was coupled to the surface of sterically stabilized liposomes loaded with doxorubicin. Cell lines from different tumor entities were investigated for liposomal association studies in vitro. For in vivo experiments, neuroendocrine tumor xenografts were used for evaluation of pharmacokinetic and therapeutic properties of the novel compound. Results: Immunohistochemistry revealed significant IGFI-R overexpression in all investigated GEP-NETs (n = 59; staining index, 229.1 +/- 3.1%) in comparison with normal tissues (115.7 +/- 3.7%). Furthermore, anti-IGFI-R immunoliposomes displayed specific tumor cell association (44.2 +/- 1.6% vs. IgG liposomes, 0.8 +/- 0.3%; P < 0.0001) and internalization in human neuroendocrine tumor cells in vitro and superior antitumor efficacy in vivo (life span 31.5 +/- 2.2 d vs. untreated control, 19 +/- 0.6, P = 0.008). Conclusion: IGFI-R overexpression seems to be a common characteristic of otherwise heterogenous NETs. Novel anti-IGFI-R immunoliposomes have been developed and successfully tested in a preclinical model for human GEP-NETs. Moreover in vitro experiments indicate that usage of this agent could also present a promising approach for other tumor entities.

Comparative Study of Informal Health Care Networks and Elderly Health Status in Argentina and Cuba

The objective of this study is to evaluate the impact of informal care support networks on the health status, life satisfaction, happiness and anxiety of elderly individuals in Argentina and Cuba. Recent economic changes, demographic changes, the structure of families and changes in women?s labor participation have affected the availability of informal care. Additionally, the growing number of elderly as a percentage of total population has significant implications for both formal and informal care in Argentina and Cuba. Methods: The SABE - Survey on Health, Well-Being, and Aging in Latin America and the Caribbean, 2000 was used as the data source. The survey has a sample of 10,656 individuals aged 60 years and older residing in private households occupied by permanent dwellers in 7 cities in the Latin American and Caribbean region. My study will focus on the Buenos Aires and Havana samples in which there were 1043 individuals and 1905 individuals respectively. General sampling design was used to establish comparability between countries. Individuals requiring assistance are surveyed on their source of help and the relative impact of informal versus paid help is measured for this group. Other measures of social support (number of living children, companionship and number of individuals living in the same dwelling) are used to measure networks for the full sample. Multivariate probit regression analyses were run separately for Cuba and for Argentina to evaluate the marginal impacts of the types of social support on health status, life satisfaction, happiness and anxiety. Results: For Argentina, almost all of the family help variables positively impact good health. Getting help from most other members of the family negatively impacts satisfaction with life. Happiness is affected differently by each of the family help variables but community support increases the likelihood of being happy. Although none of the family or community help variables show statistical significance, most negatively affect anxiety levels. In Cuba, all of the social support variables have a positive marginal impact on the health status of the elderly. In this case, some of the family and community help variables have a negative marginal impact on life satisfaction; however, it appears that having those closest to the elderly, children, spouse, or other family, positively impacts life satisfaction. Most of the support variables negatively impact happiness. Receiving help from a child, spouse or parent is associated with a marginal increase in anxiety, whereas receiving help from a grandchild, another family member or a friend actually reduces anxiety. Discussion: The study highlights the necessity for enhancing the coordination of various care networks in order to provide adequate care and reduce the burdens of old age on the individual, family and society and the need for consistent support for the caregivers. More qualitative work should be done to identify how support is given and what comprises the support. The constant change and advancement of the world, and the growth of the Latin American and Caribbean region, suggests that more updates studies need to be done.

Training in Mental Health: Evaluation of the Telephone Conference Network

The Telephone Conference Network, sponsored by The Pennsylvania State University's Coordinating Council for Health Care, is designed as a cost-effective format for providing inservice training in geriatric mental health for individuals who serve the elderly. Institutions which subscribe to the Telephone Conference Network are equipped with a conference speaker and telephone hook-up providing a two-way line of communication, and may choose from a variety of inservice programs. Mailed evaluations were completed by participants (N=73) in the "Skills to Manage Moods" program, a series of four 1-hour sessions designed to teach participants the skills needed to help patients cope with depression and to deliver the program to others. The majority of respondents reported high levels of satisfaction with the Telephone Conference Network system and the specific program in which they participated. Although 85 percent reported that they would be able to use the skills learned in the program on the job, 50 percent reported that they would not be interested in teaching these skills to others. The convenience and efficiency of the Telephone Conference Network were the most frequently mentioned strengths of the system, while the physical facilities and the program delivery format adopted by the individual institutions were the most frequently mentioned weaknesses. These data suggested several recommendations for Network subscribers and for professionals offering telephone conference programs, including ensuring optimal class enrollment and adequate physical facilities, and participant involvement in program implementation.

Does Mental Illness Affect Consumer Direction of Community-Based Care? Lessons From the Arkansas Cash and Counseling Program

Purpose: Previous research from the Cash and Counseling Demonstration and Evaluation (CCDE) in Arkansas, New Jersey, and Florida suggests that giving consumers control over their personal care greatly increases their satisfaction and improves their outlook on life. Still, some argue that consumerdirected care may not be appropriate for consumers with intellectual disabilities or mental health diagnoses. This study examined how Cash and Counseling— a new option allowing consumers to manage an individualized budget equivalent to what agencies would have spent on their care—changes the way consumers with mental health diagnoses meet their personal care needs and how that affects their wellbeing. Design and Methods: Using the Arkansas CCDE baseline and the 9-month follow-up data for individuals in the treatment and control groups, we compared and contrasted the experience of elderly consumers with and without mental health diagnoses utilizing logit regression. Results: After examining several outcome measures, including satisfaction with care arrangements and the paid caregiver’s reliability and schedule, unmet needs, and satisfaction with the relationship with paid caregivers, this study found evidence that, from the perspective of consumers, the Cash and Counseling program works well for participants with mental health diagnoses. Implications: Considering the growing need for long-term-care services and the limited resources available, a consumer-directed option makes sense, and it can be a valuable alternative for persons with mental health needs.

Development of Socio-Economic Behaviour and Attitudes of Baltic Nationalities: Perspectives for Integration with Europe

This project is the third stage of a comparative research project, The New Baltic Barometer, which was carried out simultaneously with the "New Democracies Barometer" of the Paul Lazerfeld Society (Vienna) and The Russian Barometer. It studied the opinion and behaviour of the largest Baltic ethnic groups (Estonians, Latvians, Lithuanians). The main focus was on the attitudes of Baltic residents towards the changes in the economic and political system, attitudes towards political values, political trust, and attitudes to the Baltic countries joining the European Union. An analysis of macroeconomic indicators of the Baltic states made it possible to deduce the link between the country's economic development, and satisfaction with the political regime and attitudes towards democratic values. The study analysed the conditions for the democratisation of society, i.e. the development of culture and public opinion in the Baltic states. Attention was also paid to the development of a social network of individuals, showing the transition from informal networks to impersonal institutions. The group concluded that the participation of residents in formal organisations, NGOs in particular, considerably fosters political trust and also increases political efficacy. Participation in formal organisations also reduces the importance of esteem for an authoritarian leader.