Synthesis and immunological characterization of 104-mer and 102-mer peptides corresponding to the N- and C-terminal regions of the Plasmodium falciparum CS protein.

We investigated the immunogenicity and the conformational properties of the non-repetitive sequences of the Plasmodium falciparum circumsporozoite (CS) protein. Two polypeptides of 104 and 102 amino acids long, covering, respectively, the N- and C-terminal regions of the CS protein, were synthesized using solid phase Fmoc chemistry. The crude polypeptides were purified by a combination of size exclusion chromatography and RP-HPLC. Sera of mice immunized with the free polypeptides emulsified in incomplete Freund's adjuvant strongly reacted with the synthetic polypeptides as well as with native CS protein as judged by ELISA and IFAT assays. Most importantly, these antisera inhibited the sporozoite invasion of hepatoma cells. In addition, sera derived from donors living in a malaria endemic area recognized the CS 104- and 102-mers. Conformational studies of the CS polypeptides were also performed by circular dichroism spectroscopy showing the presence of a weakly ordered structure that can be increased by addition of trifluoroethanol. The obtained results indicate that the synthetic CS polypeptides and the natural CS protein share some common antigenic determinants and probably have similar conformation. The approach used in this study might be useful for the development of a synthetic malaria vaccine.

Cardiovascular disease and the changing face of global public health : a focus on low and middle income countries

Eighty percent of the global 17 million deaths due to cardiovascular disease (CVD) occur in low and middle income countries (LMICs). The burden of CVD and other noncommunicable diseases (NCDs) is expected to markedly increase because of the global aging of the population and increasing exposure to detrimental lifestyle-related risk in LMICs. Interventions to reduce four main risks related to modifiable behaviors (tobacco use, unhealthy diet, low physical activity and excess alcohol consumption) are key elements for effective primary prevention of the four main NCDs (CVD, cancer, diabetes and chronic pulmonary disease). These behaviors are best improved through structural interventions (e.g., clean air policy, taxes on cigarettes, new recipes for processed foods with reduced salt and fat, urban shaping to improve mobility, etc.). In addition, health systems in LMICs should be reoriented to deliver integrated cost-effective treatment to persons at high risk at the primary health care level. The full implementation of a small number of highly cost effective, affordable and scalable interventions ("best buys") is likely to be the necessary and sufficient ingredient for curbing NCDs in LMICs. NCDs are both a cause and a consequence of poverty. It is therefore important to frame NCD prevention and control within the broader context of social determinants and development agenda. The recent emphasis on NCDs at a number of health and economic forums (including the September 2011 High Level Meeting on NCDs at the United Nations) provides a new opportunity to move the NCD agenda forward in LMICs.

Conventional and novel cardiovascular risk factors in young Finns and their associations with structural and functional vascular changes of subclinical atherosclerosis. The Cardiovascular Risk in Young Finns Study

Background: Atherosclerosis begins in early life progressing from asymptomatic to symptomatic as we age. Although substantial progress has been made in identifying the determinants of atherosclerosis in middle to older age adults at increased cardiovascular risk, there is lack of data examining determinants and prediction of atherosclerosis in young adults. Aims: The current study was designed to investigate levels of cardiovascular risk factors in young adults, subclinical measures of atherosclerosis, and prediction of subclinical arterial changes with conventional risk factor measures and novel metabolic profiling of serum samples. Subjects and Methods: This thesis utilised data from the follow-ups performed in 2001 and 2007 in the Cardiovascular Risk in Young Finns study, a Finnish population-based prospective cohort study that examined 2,204 subjects who were aged 30-45 years in 2007. Subclinical atherosclerosis was studied using noninvasive ultrasound measurements of carotid intima-media thickness (IMT), carotid arterial distensibility (CDist) and brachial flow-mediated dilation (FMD). Measurements included conventional risk factors and metabolic profiling using highthroughput nuclear magnetic resonance (NMR) methods that provided data on 42 lipid markers and 16 circulating metabolites. Results: Trends in lipids were favourable between 2001 and 2007, whereas waist circumference, fasting glucose, and blood pressure levels increased. To study the stability of noninvasive ultrasound markers, 6-year tracking (the likelihood to maintain the original fractile over time) in 6 years was examined. IMT tracked more strongly than CDist and FMD. Cardiovascular risk scores (Framingham, SCORE, Finrisk, Reynolds and PROCAM) predicted subclinical atherosclerosis equally. Lipoprotein subclass testing did not improve the prediction of subclinical atherosclerosis over and above conventional risk factors. However, circulating metabolites improved risk stratification. Tyrosine and docosahexaenoic acid were found to be novel biomarkers of high IMT. Conclusions: Prediction of cardiovascular risk in young Finnish adults can be performed with any of the existing risk scores. The addition of metabonomics to risk stratification improves prediction of subclinical changes and enables more accurate targeting of prevention at an early stage.

Design and evaluation of web interface signs to improve web usability : a semiotic framework

Technological innovations, the development of the internet, and globalization have increased the number and complexity of web applications. As a result, keeping web user interfaces understandable and usable (in terms of ease-of-use, effectiveness, and satisfaction) is a challenge. As part of this, designing userintuitive interface signs (i.e., the small elements of web user interface, e.g., navigational link, command buttons, icons, small images, thumbnails, etc.) is an issue for designers. Interface signs are key elements of web user interfaces because ‘interface signs’ act as a communication artefact to convey web content and system functionality, and because users interact with systems by means of interface signs. In the light of the above, applying semiotic (i.e., the study of signs) concepts on web interface signs will contribute to discover new and important perspectives on web user interface design and evaluation. The thesis mainly focuses on web interface signs and uses the theory of semiotic as a background theory. The underlying aim of this thesis is to provide valuable insights to design and evaluate web user interfaces from a semiotic perspective in order to improve overall web usability. The fundamental research question is formulated as What do practitioners and researchers need to be aware of from a semiotic perspective when designing or evaluating web user interfaces to improve web usability? From a methodological perspective, the thesis follows a design science research (DSR) approach. A systematic literature review and six empirical studies are carried out in this thesis. The empirical studies are carried out with a total of 74 participants in Finland. The steps of a design science research process are followed while the studies were designed and conducted; that includes (a) problem identification and motivation, (b) definition of objectives of a solution, (c) design and development, (d) demonstration, (e) evaluation, and (f) communication. The data is collected using observations in a usability testing lab, by analytical (expert) inspection, with questionnaires, and in structured and semi-structured interviews. User behaviour analysis, qualitative analysis and statistics are used to analyze the study data. The results are summarized as follows and have lead to the following contributions. Firstly, the results present the current status of semiotic research in UI design and evaluation and highlight the importance of considering semiotic concepts in UI design and evaluation. Secondly, the thesis explores interface sign ontologies (i.e., sets of concepts and skills that a user should know to interpret the meaning of interface signs) by providing a set of ontologies used to interpret the meaning of interface signs, and by providing a set of features related to ontology mapping in interpreting the meaning of interface signs. Thirdly, the thesis explores the value of integrating semiotic concepts in usability testing. Fourthly, the thesis proposes a semiotic framework (Semiotic Interface sign Design and Evaluation – SIDE) for interface sign design and evaluation in order to make them intuitive for end users and to improve web usability. The SIDE framework includes a set of determinants and attributes of user-intuitive interface signs, and a set of semiotic heuristics to design and evaluate interface signs. Finally, the thesis assesses (a) the quality of the SIDE framework in terms of performance metrics (e.g., thoroughness, validity, effectiveness, reliability, etc.) and (b) the contributions of the SIDE framework from the evaluators’ perspective.

Diversification In Employment Structure And Status Of Rural Women Workers In Ernakulam District

The basic objective of the present study has been to observe the process and pattern of employment diversification among the rural women workers in Ernakulam district. The evidences are that the women workers in the rural areas of the state are being increasingly diversified into the tertiary sector. The clear cut evidence for the fact that in Kerala non-agricultural employment of rural women is increasing with more and more of them getting diversified into the tertiary sector. The women get more self esteem and recognition in terms of the work being done by them. In the urban areas of the state as a poverty eradicating measure the Kerala government has already introduced a new scheme under the banner of Kudumbasree. Another fact noticed in the study that the sectoral shift of women workers has posed a grave problem to the agricultural sector. The reluctance of workers to do manual jobs on land and the prevalence of high wages among the agricultural labours has left many a cultivable area fallow or has induced farmers to shift to less labour –intensive crops. The situation is expected to worsen in future as even the high wages fail to attract the young generation to this sector. To conclude the study has fulfilled all its objectives, viz; highlighting the rural employment structure in Kerala, examining the process, pattern, determinants and consequences of diversification among rural women workers in the sample villages. Being the first of its kind at the micro level in the state it contributes to the available literature in the area enriching the database that is crucially lacking for devising projects at the village and block-level. There exists ample scope for future research of similar nature in an urban background where the secondary data-sources are hinding towards a reversal of trends from non-agriculture to agriculture.

Technological change and the challenges for regional development: building social capital in less-favoured regions

The relevance of regional policy for less favoured regions (LFRs) reveals itself when policy-makers must reconcile competitiveness with social cohesion through the adaptation of competition or innovation policies. The vast literature in this area generally builds on an overarching concept of ‘social capital’ as the necessary relational infrastructure for collective action diversification and policy integration, in a context much influenced by a dynamic of industrial change and a necessary balance between the creation and diffusion of ‘knowledge’ through learning. This relational infrastructure or ‘social capital’ is centred on people’s willingness to cooperate and ‘envision’ futures as a result of “social organization, such as networks, norms and trust that facilitate action and cooperation for mutual benefit” (Putnam, 1993: 35). Advocates of this interpretation of ‘social capital’ have adopted the ‘new growth’ thinking behind ‘systems of innovation’ and ‘competence building’, arguing that networks have the potential to make both public administration and markets more effective as well as ‘learning’ trajectories more inclusive of the development of society as a whole. This essay aims to better understand the role of ‘social capital’ in the production and reproduction of uneven regional development patterns, and to critically assess the limits of a ‘systems concept’ and an institution-centred approach to comparative studies of regional innovation. These aims are discussed in light of the following two assertions: i) learning behaviour, from an economic point of view, has its determinants, and ii) the positive economic outcomes of ‘social capital’ cannot be taken as a given. It is suggested that an agent-centred approach to comparative research best addresses the ‘learning’ determinants and the consequences of social networks on regional development patterns. A brief discussion of the current debate on innovation surveys has been provided to illustrate this point.

Isolation from a sheep of an attaching and effacing Escherichia coli O115:H- with a novel combination of virulence factors

Attaching and effacing (AE) lesions were observed in the caecum, proximal colon and rectum of one of four lambs experimentally inoculated at 6 weeks. of age with Escherichia coli O157:H7. However, the attached bacteria did not immunostain with O157-specific antiserum. Subsequent bacteriological analysis of samples from this animal yielded two E. coli O115:H- strains, one from the colon (CO) and one from the rectum (RC), and those bacteria forming the AE lesions were shown to be of the O115 serogroup by immunostaining. The O115:H(-)isolates formed microcolonies and attaching and effacing lesions, as demonstrated by the fluorescence actin staining test, on HEp-2 tissue culture cells. Both isolates were confirmed by PCR to encode the epsilon (epsilon) subtype of intimin. Supernates of both O115:H- isolates induced cytopathic effects on Vero cell monolayers, and PCR analysis verified that both isolates encoded EAST1, CNF1 and CNF2 toxins but not Shiga-like toxins. Both isolates harboured similar sized plasmids but-PCR analysis indicated that only one of the O115:H- isolates (CO) possessed the plasmid-associated virulence determinants ehxA and etpD. Neither strain possessed the espP, katP or bfpA plasmid-associated virulence determinants. These E. coli O115:H- strains exhibited a novel combination of virulence determinants and are the first isolates found to possess both CNF1 and CNF2.

Characterisation of attaching-effacing Escherichia coli isolated from animals at slaughter in England and Wales

Escherichia coli isolates were recovered from faecal samples taken from cattle, sheep and pigs at slaughter in England and Wales. Isolates (n = 1227) selected at random from this collection were each hybridised in colony dot-blot experiments with an eae gene probe that presumptively identified attaching-effacing E. coli (AEEC). Of the 99 (8.1%) eae positive isolates 72 were of ovine origin, 24 were of bovine origin and three of porcine origin. None were typed as O157:H7 whereas 78 were assigned to 23 serogroups and 21 were untypable. The most frequently isolated eae positive serogroups were O156 (10), O26 (8), O103 (8), O108 (7) O56 (6) and O168 (6) of which serogroups O103 and O156 only were recovered from all three animal species. In tissue culture adherence assays, 36 representatives of eae positive isolates of all serogroups and host of origin tested induced intimate attachment with varying degrees of actin accumulation and pedestal formation in the HEp-2 cells. The identity of the eae type for these 36 was determined by specific PCR and the most prevalent intimin types were caebeta (15), eaegamma (12) and eaeepsilon (4). Isolates were examined by PCR for the presence of other virulence determinants and five possessed stx1 but none possessed stx2. One O115 eaeepsilon isolate possessed cnf1 and 2, hlyA, etpD and katP genes which is a novel combination of virulence determinants.

Rural-urban disparities in child nutrition in Bangladesh and Nepal

Background The persistence of rural-urban disparities in child nutrition outcomes in developing countries alongside rapid urbanisation and increasing incidence of child malnutrition in urban areas raises an important health policy question - whether fundamentally different nutrition policies and interventions are required in rural and urban areas. Addressing this question requires an enhanced understanding of the main drivers of rural-urban disparities in child nutrition outcomes especially for the vulnerable segments of the population. This study applies recently developed statistical methods to quantify the contribution of different socio-economic determinants to rural-urban differences in child nutrition outcomes in two South Asian countries – Bangladesh and Nepal. Methods Using DHS data sets for Bangladesh and Nepal, we apply quantile regression-based counterfactual decomposition methods to quantify the contribution of (1) the differences in levels of socio-economic determinants (covariate effects) and (2) the differences in the strength of association between socio-economic determinants and child nutrition outcomes (co-efficient effects) to the observed rural-urban disparities in child HAZ scores. The methodology employed in the study allows the covariate and coefficient effects to vary across entire distribution of child nutrition outcomes. This is particularly useful in providing specific insights into factors influencing rural-urban disparities at the lower tails of child HAZ score distributions. It also helps assess the importance of individual determinants and how they vary across the distribution of HAZ scores. Results There are no fundamental differences in the characteristics that determine child nutrition outcomes in urban and rural areas. Differences in the levels of a limited number of socio-economic characteristics – maternal education, spouse’s education and the wealth index (incorporating household asset ownership and access to drinking water and sanitation) contribute a major share of rural-urban disparities in the lowest quantiles of child nutrition outcomes. Differences in the strength of association between socio-economic characteristics and child nutrition outcomes account for less than a quarter of rural-urban disparities at the lower end of the HAZ score distribution. Conclusions Public health interventions aimed at overcoming rural-urban disparities in child nutrition outcomes need to focus principally on bridging gaps in socio-economic endowments of rural and urban households and improving the quality of rural infrastructure. Improving child nutrition outcomes in developing countries does not call for fundamentally different approaches to public health interventions in rural and urban areas.

Essays on labour market dualisation in Western Europe: active labour market policies, temporary work regulation and inequality

European labour markets are increasingly divided between insiders in full-time permanent employment and outsiders in precarious work or unemployment. Using quantitative as well as qualitative methods, this thesis investigates the determinants and consequences of labour market policies that target these outsiders in three separate papers. The first paper looks at Active Labour Market Policies (ALMPs) that target the unemployed. It shows that left and right-wing parties choose different types of ALMPs depending on the policy and the welfare regime in which the party is located. These findings reconcile the conflicting theoretical expectations from the Power Resource approach and the insider-outsider theory. The second paper considers the regulation and protection of the temporary work sector. It solves the puzzle of temporary re-regulation in France, which contrasts with most other European countries that have deregulated temporary work. Permanent workers are adversely affected by the expansion of temporary work in France because of general skills and low wage coordination. The interests of temporary and permanent workers for re-regulation therefore overlap in France and left governments have an incentive to re-regulate the sector. The third paper then investigates what determines inequality between median and bottom income workers. It shows that non-inclusive economic coordination increases inequality in the absence of compensating institutions such as minimum wage regulation. The deregulation of temporary work as well as spending on employment incentives and rehabilitation also has adverse effects on inequality. Thus, policies that target outsiders have important economic effects on the rest of the workforce. Three broader contributions can be identified. First, welfare state policies may not always be in the interests of labour, so left parties may not always promote them. Second, the interests of insiders and outsiders are not necessarily at odds. Third, economic coordination may not be conducive to egalitarianism where it is not inclusive.

Essays in taxation and savings

Esta tese é composta por três artigos. Dois deles investigam assuntos afeitos a tributação e o terceiro é um artigo sobre o tema “poupança”'. Embora os objetos de análise sejam distintos, os três possuem como característica comum a aplicação de técnicas de econometria de dados em painel a bases de dados inéditas. Em dois dos artigos, utiliza-se estimação por GMM em modelos dinâmicos. Por sua vez, o artigo remanescente é uma aplicação de modelos de variável dependente latente. Abaixo, apresenta-se um breve resumo de cada artigo, começando pelos dois artigos de tributação, que dividem uma seção comum sobre o ICMS (o imposto estadual sobre valor adicionado) e terminando com o artigo sobre poupança. O primeiro artigo analisa a importância da fiscalização como instrumento para deter a evasão de tributos e aumentar a receita tributária, no caso de um imposto sobre valor adicionado, no contexto de um país em desenvolvimento. O estudo é realizado com dados do estado de São Paulo. Para tratar questões relativas a endogeneidade e inércia na série de receita tributária, empregam-se técnicas de painel dinâmico. Utiliza-se como variáveis de controle o nível do PIB regional e duas proxies para esforço fiscal: a quantidade e o valor das multas tributárias. Os resultados apontam impacto significativo do esforço fiscal nas receitas tributárias. O artigo evidencia, indiretamente, a forma como a evasão fiscal é afetada pela penalidade aplicada aos casos de sonegação. Suas conclusões também são relevantes no contexto das discussões sobre o federalismo fiscal brasileiro, especialmente no caso de uma reforma tributária potencial. O segundo artigo examina uma das principais tarefas das administrações tributárias: a escolha periódica de contribuintes para auditoria. A melhora na eficiência dos mecanismos de seleção de empresas tem o potencial de impactar positivamente a probabilidade de detecção de fraudes fiscais, provendo melhor alocação dos escassos recursos fiscais. Neste artigo, tentamos desenvolver este mecanismo calculando a probabilidade de sonegação associada a cada contribuinte. Isto é feito, no universo restrito de empresas auditadas, por meio da combinação “ótima” de diversos indicadores fiscais existentes e de informações dos resultados dos procedimentos de auditoria, em modelos de variável dependente latente. Após calculados os coeficientes, a probabilidade de sonegação é calculada para todo o universo de contribuintes. O método foi empregado em um painel com micro-dados de empresas sujeitas ao recolhimento de ICMS no âmbito da Delegacia Tributária de Guarulhos, no estado de São Paulo. O terceiro artigo analisa as baixas taxas de poupança dos países latino-americanos nas últimas décadas. Utilizando técnicas de dados em painel, identificam-se os determinantes da taxa de poupança. Em seguida, faz-se uma análise contrafactual usando a China, que tem apresentado altas taxas de poupança no mesmo período, como parâmetro. Atenção especial é dispensada ao Brasil, que tem ficado muito atrás dos seus pares no grupo dos BRICs neste quesito. O artigo contribui para a literatura existente em vários sentidos: emprega duas amplas bases de dados para analisar a influência de uma grande variedade de determinantes da taxa de poupança, incluindo variáveis demográficas e de previdência social; confirma resultados previamente encontrados na literatura, com a robustez conferida por bases de dados mais ricas; para alguns países latino-americanos, revela que as suas taxas de poupança tenderiam a aumentar se eles tivessem um comportamento mais semelhante ao da China em outras áreas, mas o incremento não seria tão dramático.

The work and health process in the sugarcane agroindustry in Franca, Brazil

This study aimed to discuss the interrelation between social determinants and the health conditions of workers in the sugarcane agroindustry in the region of Franca, in the countryside of São Paulo State, Brazil, from 2005 to 2006, considering the present socio-economic, historical, political and cultural conditions.

Savings, investment and growth in the global age: analytical and policy issues

Includes bibliography

Brazilian Longitudinal Study of Adult Health (ELSA-Brasil): Objectives and Design

Although low- and middle-income countries still bear the burden of major infectious diseases, chronic noncommunicable diseases are becoming increasingly common due to rapid demographic, epidemiologic, and nutritional transitions. However, information is generally scant in these countries regarding chronic disease incidence, social determinants, and risk factors. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) aims to contribute relevant information with respect to the development and progression of clinical and subclinical chronic diseases, particularly cardiovascular diseases and diabetes. In this report, the authors delineate the study's objectives, principal methodological features, and timeline. At baseline, ELSA-Brasil enrolled 15,105 civil servants from 5 universities and 1 research institute. The baseline examination (2008-2010) included detailed interviews, clinical and anthropometric examinations, an oral glucose tolerance test, overnight urine collection, a 12-lead resting electrocardiogram, measurement of carotid intima-media thickness, echocardiography, measurement of pulse wave velocity, hepatic ultrasonography, retinal fundus photography, and an analysis of heart rate variability. Long-term biologic sample storage will allow investigation of biomarkers that may predict cardiovascular diseases and diabetes. Annual telephone surveillance, initiated in 2009, will continue for the duration of the study. A follow-up examination is scheduled for 2012-2013.

The drivers and implications of environmental innovations: European evidence at different levels of analysis

The present work is a collection of three essays devoted at understanding the determinants and implications of the adoption of environmental innovations EI by firms, by adopting different but strictly related schumpeterian perspectives. Each of the essays is an empirical analysis that investigates one original research question, formulated to properly fill the gaps that emerged in previous literature, as the broad introduction of this thesis outlines. The first Chapter is devoted at understanding the determinants of EI by focusing on the role that knowledge sources external to the boundaries of the firm, such as those coming from business suppliers or customers or even research organizations, play in spurring their adoption. The second Chapter answers the question on what induces climate change technologies, adopting regional and sectoral lens, and explores the relation among green knowledge generation, inducement in climate change and environmental performances. Chapter 3 analyzes the economic implications of the adoption of EI for firms, and proposes to disentangle EI by different typologies of innovations, such as externality reducing innovations and energy and resource efficient innovations. Each Chapter exploits different dataset and heterogeneous econometric models, that allow a better extension of the results and to overcome the limits that the choice of one dataset with respect to its alternatives engenders. The first and third Chapter are based on an empirical investigation on microdata, i.e. firm level data extracted from innovation surveys. The second Chapter is based on the analysis of patent data in green technologies that have been extracted by the PATSTAT and REGPAT database. A general conclusive Chapter will follow the three essays and will outline how each Chapter filled the research gaps that emerged, how its results can be interpreted, which policy implications can be derived and which are the possible future lines of research in the field.