Historical review of clinical vaccine studies at Oswaldo Cruz Institute and Oswaldo Cruz Foundation - technological development issues

This paper presents, from the perspective of technological development and production, the results of an investigation examining 61 clinical studies with vaccines conducted in Brazil between 1938-2013, with the participation of the Oswaldo Cruz Institute (IOC) and the Oswaldo Cruz Foundation (Fiocruz). These studies have been identified and reviewed according to criteria, such as the kind of vaccine (viral, bacterial, parasitic), their rationale, design and methodological strategies. The results indicate that IOC and Fiocruz have accumulated along this time significant knowledge and experience for the performance of studies in all clinical phases and are prepared for the development of new vaccines products and processes. We recommend national policy strategies to overcome existing regulatory and financing constraints.

Immunoregulation in human malaria: the challenge of understanding asymptomatic infection

Asymptomatic Plasmodium infection carriers represent a major threat to malaria control worldwide as they are silent natural reservoirs and do not seek medical care. There are no standard criteria for asymptomaticPlasmodium infection; therefore, its diagnosis relies on the presence of the parasite during a specific period of symptomless infection. The antiparasitic immune response can result in reducedPlasmodium sp. load with control of disease manifestations, which leads to asymptomatic infection. Both the innate and adaptive immune responses seem to play major roles in asymptomatic Plasmodiuminfection; T regulatory cell activity (through the production of interleukin-10 and transforming growth factor-β) and B-cells (with a broad antibody response) both play prominent roles. Furthermore, molecules involved in the haem detoxification pathway (such as haptoglobin and haeme oxygenase-1) and iron metabolism (ferritin and activated c-Jun N-terminal kinase) have emerged in recent years as potential biomarkers and thus are helping to unravel the immune response underlying asymptomatic Plasmodium infection. The acquisition of large data sets and the use of robust statistical tools, including network analysis, associated with well-designed malaria studies will likely help elucidate the immune mechanisms responsible for asymptomatic infection.

Understanding the development of the ESDP: Perspectives and insights from historical institutionalism and theories of learning

How can we best understand the emergence of the European Security and Defence Policy (ESDP)? This paper applies the theories of historical institutionalism and experiential learning to offer a dynamic conceptualisation of moves towards an ESDP which highlights some of the causal factors that a more temporally-restricted analysis would miss. It firstly shows how the institutional and functional expansion of European Political Cooperation (EPC) over the course of the 1970s and 80s gave rise to a context in which the development of a security and defence dimension came to be viewed as more logical and even necessary. It then goes on to analyse some of the external factors (in the form of actors, events and institutions) that further pushed in this direction and proved to influence the policy’s subsequent evolution. The paper is therefore intended to act as a first-step to understanding the ESDP’s development from this perspective.

Disease in the dark: molecular characterization of Polychromophilus murinus in temperate zone bats revealed a worldwide distribution of this malaria-like disease.

For a better understanding of the complex coevolutionary processes between hosts and parasites, accurate identification of the actors involved in the interaction is of fundamental importance. Blood parasites of the Order Haemosporidia, responsible for malaria, have become the focus of a broad range of studies in evolutionary biology. Interestingly, molecular-based studies on avian malaria have revealed much higher species diversity than previously inferred with morphology. Meanwhile, studies on bat haemosporidian have been largely neglected. In Europe, only one genus (Polychromophilus) and two species have been morphologically described. To evaluate the presence of potential cryptic species and parasite prevalence, we undertook a molecular characterization of Polychromophilus in temperate zone bats. We used a nested-PCR approach on the cytochrome b mitochondrial gene to detect the presence of parasites in 237 bats belonging to four different species and in the dipteran bat fly Nycteribia kolenatii, previously described as being the vector of Polychromophilus. Polychromophilus murinus was found in the four bat species and in the insect vector with prevalence ranging from 4% for Myotis myotis to 51% for M. daubentoni. By sequencing 682 bp, we then investigated the phylogenetic relationships of Polychromophilus to other published malarial lineages. Seven haplotypes were found, all very closely related, suggesting the presence of a single species in our samples. These haplotypes formed a well-defined clade together with Haemosporidia of tropical bats, revealing a worldwide distribution of this parasite mostly neglected by malarial studies since the 1980s.

Malaria vaccine candidate: design of a multivalent subunit α-helical coiled coil poly-epitope.

A new strategy for the rapid identification of new malaria antigens based on protein structural motifs was previously described. We identified and evaluated the malaria vaccine potential of fragments of several malaria antigens containing α-helical coiled coil protein motifs. By taking advantage of the relatively short size of these structural fragments, we constructed different poly-epitopes in which 3 or 4 of these segments were joined together via a non-immunogenic linker. Only peptides that are targets of human antibodies with anti-parasite in vitro biological activities were incorporated. One of the constructs, P181, was well recognized by sera and peripheral blood mononuclear cells (PBMC) of adults living in malaria-endemic areas. Affinity purified antigen-specific human antibodies and sera from P181-immunized mice recognised native proteins on malaria-infected erythrocytes in both immunofluorescence and western blot assays. In addition, specific antibodies inhibited parasite development in an antibody dependent cellular inhibition (ADCI) assay. Naturally induced antigen-specific human antibodies were at high titers and associated with clinical protection from malaria in longitudinal follow-up studies in Senegal.

Historical Development and Applications of the EPIC and APEX Models, June 2005

The development of the field-scale Erosion Productivity Impact Calculator (EPIC) model was initiated in 1981 to support assessments of soil erosion impacts on soil productivity for soil, climate, and cropping conditions representative of a broad spectrum of U.S. agricultural production regions. The first major application of EPIC was a national analysis performed in support of the 1985 Resources Conservation Act (RCA) assessment. The model has continuously evolved since that time and has been applied for a wide range of field, regional, and national studies both in the U.S. and in other countries. The range of EPIC applications has also expanded greatly over that time, including studies of (1) surface runoff and leaching estimates of nitrogen and phosphorus losses from fertilizer and manure applications, (2) leaching and runoff from simulated pesticide applications, (3) soil erosion losses from wind erosion, (4) climate change impacts on crop yield and erosion, and (5) soil carbon sequestration assessments. The EPIC acronym now stands for Erosion Policy Impact Climate, to reflect the greater diversity of problems to which the model is currently applied. The Agricultural Policy EXtender (APEX) model is essentially a multi-field version of EPIC that was developed in the late 1990s to address environmental problems associated with livestock and other agricultural production systems on a whole-farm or small watershed basis. The APEX model also continues to evolve and to be utilized for a wide variety of environmental assessments. The historical development for both models will be presented, as well as example applications on several different scales.

The implicit theory of historical change in the work of Alan S. Milward

Alan S. Milward was an economic historian who developed an implicit theory ofhistorical change. His interpretation which was neither liberal nor Marxist positedthat social, political, and economic change, for it to be sustainable, had to be agradual process rather than one resulting from a sudden, cataclysmicrevolutionary event occurring in one sector of the economy or society. Benignchange depended much less on natural resource endowment or technologicaldevelopments than on the ability of state institutions to respond to changingpolitical demands from within each society. State bureaucracies were fundamentalto formulating those political demands and advising politicians of ways to meetthem. Since each society was different there was no single model of developmentto be adopted or which could be imposed successfully by one nation-state onothers, either through force or through foreign aid programs. Nor coulddevelopment be promoted simply by copying the model of a more successfuleconomy. Each nation-state had to find its own response to the political demandsarising from within its society. Integration occurred when a number of nation states shared similar political objectives which they could not meet individuallybut could meet collectively. It was not simply the result of their increasinginterdependence. It was how and whether nation-states responded to thesedomestic demands which determined the nature of historical change.

Does direct democracy reduce the size of government? New evidence from historical data, 1890-2000

Using historical data for all Swiss cantons from 1890 to 2000, we estimate the causal effect of direct democracy on government spending. The main innovation in this paper is that we use fixed effects to control for unobserved heterogeneity and instrumental variables to address the potential endogeneity of institutions. We find that the budget referendum and lower costs to launch a voter initiative are effective tools in reducing canton level spending. However, we find no evidence that the budget referendum results in more decentralized government or a larger local government. Our instrumental variable estimates suggest that a mandatory budget referendum reduces the size of canton spending between 13 and 19 percent. A 1 percent lower signature requirement for the initiative reduces canton spending by up to 2 percent.

Debt sustainability in historical perspective: The role of fiscal repression

This article examines the debt history of two contenders for European hegemony: 16th-centurySpain and 18th-century Britain. We analyze their fiscal behavior using measures of overborrowingand fiscal policy functions. Our results suggest that stringency was not key for Britain ssuccess in avoiding default. Instead, fiscal repression allowed the United Kingdom to borrowat below-market rates, thereby outspending its continental rivals.

Did colonization matter for growth? An empirical exploration into the historical causes of Africa's underdevelopment

We investigate the impact of 20th--century European colonizationon growth in Africa. We find that in the 1960--88 period growth has beenfaster for dependencies than for colonies; for British and Frenchcolonies than for Portuguese, Belgian and Italian ones; and for countrieswith less economic penetration during the colonial period. On average,African growth accelerates after decolonization. Proxies for colonialheritage add explanatory power to growth regressions and make indicatorsfor human capital, political and ethnic instability lose significance.Colonial variables capture the same effects of a sub--Saharan dummy andreduce its significance when jointly included in a cross sectionalregression with 98 countries.

Historical contingency affects signaling strategies and competitive abilities in evolving populations of simulated robots.

One of the key innovations during the evolution of life on earth has been the emergence of efficient communication systems, yet little is known about the causes and consequences of the great diversity within and between species. By conducting experimental evolution in 20 independently evolving populations of cooperatively foraging simulated robots, we found that historical contingency in the occurrence order of novel phenotypic traits resulted in the emergence of two distinct communication strategies. The more complex foraging strategy was less efficient than the simpler strategy. However, when the 20 populations were placed in competition with each other, the populations with the more complex strategy outperformed the populations with the less complex strategy. These results demonstrate a tradeoff between communication efficiency and robustness and suggest that stochastic events have important effects on signal evolution and the outcome of competition between distinct populations.

First record of Coprophanaeus bellicosus (Olivier) (Coleoptera, Scarabaeidae) in a "Brejo de Altitude" forest in northeastern Brazil: a historical biogeographical approach

First record of Coprophanaeus bellicosus (Olivier) (Coleoptera, Scarabaeidae) in a "Brejo de Altitude" forest in northeastern Brazil: a historical biogeographical approach. This note presents the first record for a species of dung beetle of the genus Coprophanaeus, subgenus Megaphanaeus, in a "Brejo de Altitude" forest. Besides the new record, the paper discusses biogeographic aspects of the species and subgenus, as well as of the natural history of the "Brejos de Altitude", unique ecosystems in the northeast region of Brazil.

Stationarity analysis of historical flood series in France and Spain (14th-20th centuries)

Interdisciplinary frameworks for studying natural hazards and their temporal trends have an important potential in data generation for risk assessment, land use planning, and therefore the sustainable management of resources. This paper focuses on the adjustments required because of the wide variety of scientific fields involved in the reconstruction and characterisation of flood events for the past 1000 years. The aim of this paper is to describe various methodological aspects of the study of flood events in their historical dimension, including the critical evaluation of old documentary and instrumental sources, flood-event classification and hydraulic modelling, and homogeneity and quality control tests. Standardized criteria for flood classification have been defined and applied to the Isère and Drac floods in France, from 1600 to 1950, and to the Ter, the Llobregat and the Segre floods, in Spain, from 1300 to 1980. The analysis on the Drac and Isère data series from 1600 to the present day showed that extraordinary and catastrophic floods were not distributed uniformly in time. However, the largest floods (general catastrophic floods) were homogeneously distributed in time within the period 1600¿1900. No major flood occurred during the 20th century in these rivers. From 1300 to the present day, no homogeneous behaviour was observed for extraordinary floods in the Spanish rivers. The largest floods were uniformly distributed in time within the period 1300-1900, for the Segre and Ter rivers.