Development of an in vitro model for studying aneurysms

The aims of this project was to develop an arterial aneurysm using either enzymatic or laser degradation of the arterial wall without affecting the viability of the tissue and to cultivate the arteries under pulsatile flow conditions in a vascular bioreactor with a view to investigate the progress of the disease. Characteristics of aneurysms are the degradation of smooth muscle cells, collagen and elastin. Detached smooth muscle cells and degradation of the collagen matrix and elastin fibres were observed in arteries degraded with enzymes elastase and collagenase. Only remnants of the arterial wall were detected after cultivation. This might be a suitable model for late stage aneurysms. Arteries treated with the laser system showed no charring or heat damage of the not dissected area. Collagen matrix, smooth muscle cells and elastin fibres were intact. A clear defined cut was made in a depth of 200 μm and tissue was removed. Following cultivation of these arteries a dilation of the laser-eroded area was observed. This model can mimic atherosclerotic aneurysms, when plaques weaken the tunica media of the blood vessel wall and rupture. Limitations of this study were contamination of the bioreactor system and a low number of cultivations. The aim to generate a living arterial aneurysm in vitro was not achieved. Tissue viability decreased to the level of negative controls after cultivation.

Development of a new method for the characterisation of bioreactors concerning heat and mass transfer

Since the specific heat transfer coefficient (UA) and the volumetric mass transfer coefficient (kLa) play an important role for the design of biotechnological processes, different techniques were developed in the past for the determination of these parameters. However, these approaches often use imprecise dynamic methods for the description of stationary processes and are limited towards scale and geometry of the bioreactor. Therefore, the aim of this thesis was to develop a new method, which overcomes these restrictions. This new approach is based on a permanent production of heat and oxygen by the constant decomposition of hydrogen peroxide in continuous mode. Since the degradation of H2O2 at standard conditions only takes place by the support of a catalyst, different candidates were investigated for their potential (regarding safety issues and reaction kinetic). Manganese-(IV)-oxide was found to be suitable. To compensate the inactivation of MnO2, a continuous process with repeated feeds of fresh MnO2 was established. Subsequently, a scale-up was successfully carried out from 100 mL to a 5 litre glass bioreactor (UniVessel®)To show the applicability of this new method for the characterisation of bioreactors, it was compared with common approaches. With the newly established technique as well as with a conventional procedure, which is based on an electrical heat source, specific heat transfer coefficients were measured in the range of 17.1 – 24.8 W/K for power inputs of about 50 – 70 W/L. However, a first proof of concept regarding the mass transfer showed no constant kLa for different dilution rates up to 0.04 h-1.Based on this, consecutive studies concerning the mass transfer should be made with higher volume flows, due to more even inflow rates. In addition, further experiments are advisable, to analyse the heat transfer in single-use bioreactors and in larger common systems.

Sobre o bi-iodeto de cobre: ensaios de farmacodinamica

O Cul² prepara-se sob a forma de hidrosol cuja dosagem pode ser rigorosa. De suas propriedades quimicas já estudadas por TRAUBE é mais notavel a sensibilidade desse corpo ao oxijeno nacente. Basta em verdade 0,00001 de H²O² para que o Cul² se decomponha desprendendo-se I. Inversamente ele decompõe a agua oxijenada em solução neutra a 1 % (Perhydrol MERCK). O oxijeno do ar atmosferico só o decompõe muito lentamente. As soluções se conservam bem por 6 mezes em vidro escuro. Mesmo em 24 horas, uma corrente de ar não o altera. A ação hemolitica desse hidrosol depende principalmente da H²O distilada que entra em sua composição. Em uma solução isotonisada pelo NaCl, a ação hemolitica diminue proporcionalmente ao aumento de concentração de NaCl, ainda mesmo que se aumente a concentração em Cul². A concentração em Cul² só tem influencia manifesta sobre o fenomeno da precipitação da hemoglobina, sobre a qual ele aje como redutor. Tem ação fixadora sobre os leucocitos, e aglutinante sobre as hematias. Não destroe o fermento da fibrina nem a catalase do sangue. Precipita os albuminoides do soro, pelo menos in vitro. In vivo, esses fenomenos não são aparentes. Foi possivel a aplicação do Cul² por via venosa, sem que isso tivesse determinado acidentes nos animais experimentados (cão, cobaia, coelho, rato). Por via peritoneal não era suportado pelo coelho, nem pela cobaia, morrendo os animais dentro das primeiras 24 horas. Por via subcutanea não era tolerado facilmente por cobaias e ratos. Formava-se sempre escara no ponto da inoculação. O cão tolerava bem as inoculaçõis subcutaneas. Mostrou-se esse hidrosol ineficaz na esporotricose e tuberculose experimentais. Ao terminar, deixo aqui consignado ao distinto colega Dr. ANTONIO PINTO JNR. os meus agradecimentos pelo valioso concurso prestado em toda a parte experimental por ele acompanhada com a maior dedicação e boa vontade.

Measuring sustained superior performance at the firm level

This paper proposes a two-dimensional Strategic Performance Measure (SPM) to evaluate the achievement of sustained superior performance. This proposal builds primarily on the fact that, under the strategic management perspective, a firm's prevalent objective is the pursuit of sustained superior performance. Three basic conceptual dimensions stem from this objective: relativity, sign dependence, and dynamism. These are the foundations of the SPM, which carries out a separate evaluation of the attained superior performance and of its sustainability over time. In contrast to existing measures of performance, the SPM provides: (i) a dynamic approach by considering the progress or regress in performance over time, and (ii) a cardinal measurement of performance differences and its changes over time. The paper also proposes an axiomatic framework that a measure of strategic performance should comply with to be theoretically and managerially sound. Finally, an empirical illustration of the Spanish banking sector during 1987-1999 is herein provided by discussing some relevant cases.

A note on Spatial Autocorrelation at a Local Level

In this paper we analyze the existence of spatial autocorrelation at a local level in Catalonia using variables such as urbanisation economies, population density, human capital and firm entries. From a static approach, our results show that spatial autocorrelation is weak and diminishes as the distance between municipalities increases. From a dynamic approach, however, spatial autocorrelation increased over the period we analysed. These results are important from a policy point of view, since it is essential to know how economic activities are spatially concentrated or disseminated. Key words: spatial autocorrelation, municipalities. JEL classification: R110, R120

Human capital as a factor of growth and employment at the regional level. The case of Spain

We use statistical techniques to quantify the effects of school attainment on individual wages, participation rates and employment probabilities in Spain, and to measure the contribution of education to labour productivity at the regional level. These estimates are then combined with data on private and public expenditure on education and with information on taxes and social benefits to construct measures of the private and social returns to schooling, to explore the effects of public policies on private incentives to invest in human capital, and to analyse the long-term effects of schooling on public finances. The results are used, together with estimates of the returns to alternative assets, to draw some tentative conclusions regarding the adequacy of the aggregate investment patterns observed in the regions of Spain, and to identify changes in the design of national and EU cohesion and growth policies that may help enhance their effectiveness.

Human capital in a global and knowledge-based economy. Part 2. Asssessment at the EU country level.

This report is an extension and partial update of de la Fuente and Ciccone (2002). It constructs estimates of the private and social rates of return on schooling for fourteen EU countries using microeconometric estimates of Mincerian wage equations, the results of cross-country growth regressions and OECD data on educational expenditures, tax rates and social benefits. The results are used to draw some tentative conclusions regarding the optimality of observed investment patterns and educational subsidy levels.

Likelihood-based approaches to modeling demand for medical care

We review recent likelihood-based approaches to modeling demand for medical care. A semi-nonparametric model along the lines of Cameron and Johansson's Poisson polynomial model, but using a negative binomial baseline model, is introduced. We apply these models, as well a semiparametric Poisson, hurdle semiparametric Poisson, and finite mixtures of negative binomial models to six measures of health care usage taken from the Medical Expenditure Panel survey. We conclude that most of the models lead to statistically similar results, both in terms of information criteria and conditional and unconditional prediction. This suggests that applied researchers may not need to be overly concerned with the choice of which of these models they use to analyze data on health care demand.

Industrial location at a local level: some comments about the territorial level of the analysis

This paper contributes to the existing literature on industrial location by discussing some issues regarding the territorial levels that have been used in location analysis. We analyse which could be the advantages and disadvantages of performing locational analysis at a different local levels. We use data for new manufacturing firms located at municipality, county and travel to work areas level. We show that location determinants vary according to the territorial level used in the analysis, so we conclude that the level at which we perform the investigation should be carefully selected. Keywords: industrial location, cities, agglomeration economies, count data models.

Learning the ropes and embracing the rules: CFSP institutions as arenas for learning and strategic socialisation

The aim of this article is to analyse those situations in which learning and socialisation take place within the context of the Common Foreign and Security Policy (CFSP), in particular, at the level of experts in the Council Working Groups. Learning can explain the institutional development of CFSP and changes in the foreign policies of the Member States. Some scope conditions for learning and channels of institutionalisation are identified. Socialisation, resulting from learning within a group, is perceived as a strategic action by reflective actors. National diplomats, once they arrive in Brussels, learn the new code of conduct of their Working Groups. They are embedded in two environments and faced with two logics: the European one in the Council and the national one in the Ministries of Foreign Affairs (MFA). The empirical evidence supports the argument that neither rational nor sociological approaches alone can account for these processes.

Changes of overweight and obesity in the adult Swiss population according to educational level, from 1992 to 2007.

In many high income developed countries, obesity is inversely associated with educational level. In some countries, a widening gap of obesity between educational groups has been reported. The aim of this study was to assess trends in body mass index (BMI) and in prevalence of overweight and obesity and their association with educational level in the adult Swiss population. Four cross-sectional National health interview surveys conducted in 1992/93 (n = 14,521), 1997 (n = 12,474), 2002 (n = 18,908) and 2007 (n = 17,879) using representative samples of the Swiss population (age range 18-102 years). BMI was derived from self-reported data. Overweight was defined as BMI > or = 25 and <30 kg/m(2), and obesity as BMI > or = 30 kg/m(2). Mean (+/- standard deviation) BMI increased from 24.7 +/- 3.6 in 1992/3 to 25.4 +/- 3.6 kg/m2 in 2007 in men and 22.8 +/- 3.8 to 23.7 +/- 4.3 kg/m(2) in women. Between 1992/3 and 2007, the prevalence of overweight + obesity increased from 40.4% to 49.5% in men and from 22.3% to 31.3% in women, while the prevalence of obesity increased from 6.3% to 9.4% in men and from 4.9% to 8.5% in women. The rate of increase in the prevalence of obesity was greater between 1992/3 and 2002 (men: +0.26%/year; women: +0.31%/year) than between 2002 and 2007 (men: +0.10%/year; women: +0.10%/year). A sizable fraction (approximately 25%) of the increasing mean BMI was due to increasing age of the participants over time. The increase was larger in low than high education strata of the population. BMI was strongly associated with low educational level among women and this gradient remained fairly constant over time. A weaker similar gradient by educational level was apparent in men, but it tended to increase over time. In Switzerland, overweight and obesity increased between 1992 and 2007 and was associated with low education status in both men and women. A trend towards a stabilization of mean BMI levels was noted in most age categories since 2002. The increase in the prevalence of obesity was larger in low education strata of the population. These findings suggest that obesity preventive measures should be targeted according to educational level in Switzerland.

Impact of genetic SLC28 transporter and ITPA variants on ribavirin 21 serum level, hemoglobin drop and therapeutic response in patients with HCV infection

Background: T reatment o f chronic hepatitis C i s evolving, a nd direct acting antivirals ( DAAs) are now a dded to p egylated interferon-α ( Peg- INF-α) and ribavirin (RBV) for the treatment o f hepatitis C v irus ( HCV) genotype 1 infection. DAAs c ause d ifferent side effects and can even worsen RBV induced hemolytic anemia. T herefore, identifying host genetic d eterminants of R BV bioavailability and therapeutic e fficacy will remain crucial for individualized treatment. Recent d ata showed associations between R BV induced h emolytic anemia and genetic polymorphisms o f concentrative nucleoside transporters s uch as C NT3 (SLC28A3) and i nosine t riphosphatase (ITPA). T o analyze t he association of genetic variants of SLC28 transporters and ITPA with RBV induced hemolytic anemia and treatment o utcome. Methods: I n our study, 173 patients f rom t he S wiss Hepatitis C C ohort Study and 2 2 patients from Swiss Association for the Study of the Liver study 24 (61% HCV g enotype 1, 3 9% genotypes 2 o r 3) were analyzed for SLC28A2 single nucleotide p olymorphism (SNP) rs11854484, SLC28A3 rs56350726 and SLC28A3 rs10868138 as well as ITPA SNPs rs1127354 and rs7270101. RBV serum levels during treatment were measured in 49 patients. Results: SLC28A2 r s11854484 genotype TT was associated with significantly higher dosage- and body weight-adjusted RBV levels as compared to genotypes TC and CC (p=0.04 and p=0.02 at weeks 4 and 8, respectively). ITPA SNPs rs1127354 and rs7270101 were associated with h emolytic a nemia both in genotype as w ell as i n allelic a nalyses. SLC28A3 rs56350726 genotype TT (vs. AT/AA, RR=2.1; 95% CI 1.1-4.1) as well as the T allele (vs. A; RR=1.8, 95% CI 1.1-3.2) were associated with increased SVR rates. The combined analysis of overall ITPA activity and SLC28 v ariants together revealed n o significant a dditive effects on either treatment-related anemia or SVR. Conclusions: T he newly identified association between RBV serum levels a nd SLC28A2 rs11854484 genotype as well as the replicated association of ITPA and SLC28A3 g enetic p olymorphisms w ith RBV induced hemolytic anemia and treatment r esponse underpin the need for further studies on host genetic d eterminants of R BV bioavailability and therapeutic e fficacy f or individualized treatment of chronic hepatitis C.