Breast cancer prognostic classification in the molecular era: the role of histological grade.

Breast cancer is a heterogeneous disease with varied morphological appearances, molecular features, behavior, and response to therapy. Current routine clinical management of breast cancer relies on the availability of robust clinical and pathological prognostic and predictive factors to support clinical and patient decision making in which potentially suitable treatment options are increasingly available. One of the best-established prognostic factors in breast cancer is histological grade, which represents the morphological assessment of tumor biological characteristics and has been shown to be able to generate important information related to the clinical behavior of breast cancers. Genome-wide microarray-based expression profiling studies have unraveled several characteristics of breast cancer biology and have provided further evidence that the biological features captured by histological grade are important in determining tumor behavior. Also, expression profiling studies have generated clinically useful data that have significantly improved our understanding of the biology of breast cancer, and these studies are undergoing evaluation as improved prognostic and predictive tools in clinical practice. Clinical acceptance of these molecular assays will require them to be more than expensive surrogates of established traditional factors such as histological grade. It is essential that they provide additional prognostic or predictive information above and beyond that offered by current parameters. Here, we present an analysis of the validity of histological grade as a prognostic factor and a consensus view on the significance of histological grade and its role in breast cancer classification and staging systems in this era of emerging clinical use of molecular classifiers.

Bottled natural mineral water in catalonia: origin and geographical evolution of its consumption and production

During the second half of the nineteenth century a major mineral water bottling industry appeared in Catalonia which vigorously lasted until the first third of the 20th century. The fact that the industry appeared in Catalonia and in other parts of Europe and the United States almost at the same time and had not existed before can be explained by a series of factors which coincided in time. This situation encouraged producers to pack, transport and sell bottled water from their respective sources. Among these factors there is the rise of hygienism, very influential in Catalonia, the declining water quality due to industrialization, the increase in population density, the improvement in transport, the emergence of thermal tourism or the invention of better containers used to store water. This project aims to explain thoroughly all the mentioned factors, and to give some light to why, when and how the Catalan bottled water industry appeared.

Soins palliatifs et soins de support: à la frontière de la toute-puissance médicale [Palliative and supportive care: at the frontiers of medical omnipotence].

Cancer patients have physical, social, spiritual and emotional needs. They may suffer from severe physical symptoms, from social isolation, spiritual abandonment, and emotions such as sadness and anxiety, or feelings of deception, helplessness, anger and guilt. In some of them, the disease is rapidly progressing and ultimately they die. Their demanding care evokes intense feelings in health care providers, the more since these incurable patients represent a challenge, which could be condensed under the heading "the challenge of medical omnipotence". We suppose that the way health care providers cope with these circumstances has a profound influence on the way these patients are cared for. The attitudes towards the emerging heterogeneous movement of palliative and supportive care and towards its different models of implementation can be viewed from this point of view. We try to demonstrate these interrelations and to discuss the danger that may arise if they remain obscure and unreflected.

The EU ‘2020 Energy Initiative’: The post-Lisbon pattern of change in EU energy policy

El novembre de 2010, la Comissió Europea ha finalment donat a conèixer la seva "Energia 2020 Comunicació", un document estratègic en el marc més ampli del programa "Europa 2020". Una estratègia per al desenvolupament sostenible intel · ligent, i creixement inclusiu posa les bases d'un nou enfocament a la política d'energia a la UE. En el marc d'Europa 2020, la Iniciativa d'Energia recopila els resultats que ja s'han obtingut a través de la Estratègia de Lisboa 2000-2010, s'identifiquen les deficiències del passat i i introdueix nous objectius ambiciosos per a la UE en matèria de política energètica.

The Strategic value of European renewable energy promotion policy

Encara falta per fer possible una transformació estratègica d'Europa del sistema d'energia, però el que és de la mateixa importància com a objectius a llarg termini de la FER i Reduccions de GEH són vinculants i forts objectius d'eficiència energètica, no només per 2020, però també per al 2030, 2040 i 2050, com aquesta força ajudaria a fixar l'augment de les energies renovables en el total d'energia consum i per reduir el total Emissions de GEH d'Europa en general, i les del sector de l'energia en particular, encara sent un dels majors emissors de gasos d'efecte hivernacle de tots els sectors. La refosa Directiva, prevista per 2011/12 ha de ser un bones finestres d'oportunitat per finalment establir objectius vinculants d'eficiència energètica, l'únic pilar que encara falta en la força energia interdependents i estratègia sobre el clima de la UE, basat en la reducció de gasos d'efecte hivernacle i i l'eficiència energètica.

Mixed Blessing? EP Oversight of the ESDP and the Constitutional Treaty

As commonly held, the European Security and Defence Policy (ESDP) suffers from a “double democratic deficit”: the EP has a marginal role in the ESDP-making process and the national parliaments remain unable to account for their own government. Therefore pressure coming from these two institutions had been exercised during the Convention on the Future of Europe to improve the democratic oversight on this rapidly evolving policy. This paper investigates the innovations included in the Constitutional Treaty, focusing specifically on the new role granted to the EP. It shows that even though this text does not substantially modify the inter-institutional balance of powers in the ESDP area, the EP may take advantage of some of its articles to become an actor in the ESDP-control process in the ‘living constitution.

Analysis of multi-scale systemic risk in Brazil's financial market

This work analyzes whether the relationship between risk and returns predicted by the Capital Asset Pricing Model (CAPM) is valid in the Brazilian stock market. The analysis is based on discrete wavelet decomposition on different time scales. This technique allows to analyze the relationship between different time horizons, since the short-term ones (2 to 4 days) up to the long-term ones (64 to 128 days). The results indicate that there is a negative or null relationship between systemic risk and returns for Brazil from 2004 to 2007. As the average excess return of a market portfolio in relation to a risk-free asset during that period was positive, it would be expected this relationship to be positive. That is, higher systematic risk should result in higher excess returns, which did not occur. Therefore, during that period, appropriate compensation for systemic risk was not observed in the Brazilian market. The scales that proved to be most significant to the risk-return relation were the first three, which corresponded to short-term time horizons. When treating differently, year-by-year, and consequently separating positive and negative premiums, some relevance is found, during some years, in the risk/return relation predicted by the CAPM. However, this pattern did not persist throughout the years. Therefore, there is not any evidence strong enough confirming that the asset pricing follows the model.

Range expansion of the greater white-toothed shrew Crocidura russula in Switzerland results in local extinction of the bicoloured white-toothed shrew C-leucodon

The distribution limits of Crocidura russula (Hermann, 1780) and C. leucodon (Hermann, 1780) were investigated during an interval of 25 years in the bottom of the Rhone valley above Lake Geneva, Switzerland (total data set: 105 spatio-temporal occurrences, 1137 shrews). In 1975, the contact zone between the two species was situated in the region of Martigny. In 1999/2000, new sampling revealed three results: (1) The contact zone showed an upward shift of about 25 km. (2) In the expanded range of C. russula, the resident species has totally disappeared (confirmed by owl pellets analysis). (3) This demonstrates a dominance of C, russula over C. leucodon. Three hypotheses which may explain the range expansion of C. russula were evaluated: (1) habitat modification favouring linear dispersal due to the construction of a highway; (2) temporal event favoured by climate fluctuations, or (3) ongoing postglacial colonisation of Europe. Hypothesis 1 was rejected, because the progression of the shrews anticipated the construction. Hypothesis 3 received only weak support because range limits of C. russula in the region of Nice have been stable for thousands of years. Therefore hypothesis 2, admitting that ongoing climate change has facilitated range expansion, is the most probable.

Assessing AIDS/HIV prevention: what do we know in Europe?

An EC concerted action on the assessment of AIDS/HIV prevention strategies was conducted between 1989 and 1992. The aim of this concerted action (CA) was to bring together researchers who are active in this assessment field, make an initial appraisal of the results of AIDS prevention efforts, in various population groups in Europe and develop an assessment methodology. Five areas of study were selected for the CA: the population as a whole ("general population"), men who have sexual relations with other men, intravenous drug users, migrant populations, monitoring of sexually transmitted diseases (STDs) to determine changes in behaviour. For each of these areas, a working group composed of the leading researchers in the field in Europe was constituted and commissioned by the project administration and coordination team to collate and analyse data on prevention efforts and their assessment in different countries of Europe. This review presents the main results from the groups responsible in each area in the concerted action. A number of general conclusions from the results of this concerted action are drawn.

The roots of success: industrial growth in Italy reconsidered, 1911- 1951

This article reconsiders the growth of Italian industry from the First World War to the eve of the economic miracle, with the aid of sector-specific new value-added series, at three different price-bases. The new estimates reduce growth during the First World War, making the Italian case comparable to the other belligerent countries, while improving the performance of the 1920s. The 1929 crisis looks more profound than before, while the recovery after 1933 is now stronger. During the 1920s and the 1930s, a significant shift from traditional to more advanced activities took place: when confronted with the rest of Europe, the interwar period was a relative success, which laid the ground for the following economic boom.

Genetic studies of the Roma (Gypsies): a review

Background: Data provided by the social sciences as well as genetic research suggest that the 8-10 million Roma (Gypsies) who live in Europe today are best described as a conglomerate of genetically isolated founder populations. The relationship between the traditional social structure observed by the Roma, where the Group is the primary unit, and the boundaries, demographic history and biological relatedness of the diverse founder populations appears complex and has not been addressed by population genetic studies. Results: Recent medical genetic research has identified a number of novel, or previously known but rare conditions, caused by private founder mutations. A summary of the findings, provided in this review, should assist diagnosis and counselling in affected families, and promote future collaborative research. The available incomplete epidemiological data suggest a non-random distribution of disease-causing mutations among Romani groups.Conclusion: Although far from systematic, the published information indicates that medical genetics has an important role to play in improving the health of this underprivileged and forgotten people of Europe. Reported carrier rates for some Mendelian disorders are in the range of 5 -15%, sufficient to justify newborn screening and early treatment, or community-based education and carrier testing programs for disorders where no therapy is currently available. To be most productive, future studies of the epidemiology of single gene disorders should take social organisation and cultural anthropology into consideration, thus allowing the targeting of public health programs and contributing to the understanding of population structure and demographic history of the Roma.

Spheres of diversities: from concept to policy

This book is concerned with the diversity debate in the context of Europe.It is about diversity both as a concept and as a policy. Indeed, the epicentreof the analysis is the link between the spheres of diversity-concepts anddiversity-policies. The book explores how the concept of diversity orientatespolicies and management, and also how public/private managementfacilitates new policy orientations. As such, the book enhances conceptualthinking on diversity, but also facilitates policy thinking on the conceptinvolved in novel policy orientations towards diversity.

Genes mirror geography within Europe.

Understanding the genetic structure of human populations is of fundamental interest to medical, forensic and anthropological sciences. Advances in high-throughput genotyping technology have markedly improved our understanding of global patterns of human genetic variation and suggest the potential to use large samples to uncover variation among closely spaced populations. Here we characterize genetic variation in a sample of 3,000 European individuals genotyped at over half a million variable DNA sites in the human genome. Despite low average levels of genetic differentiation among Europeans, we find a close correspondence between genetic and geographic distances; indeed, a geographical map of Europe arises naturally as an efficient two-dimensional summary of genetic variation in Europeans. The results emphasize that when mapping the genetic basis of a disease phenotype, spurious associations can arise if genetic structure is not properly accounted for. In addition, the results are relevant to the prospects of genetic ancestry testing; an individual's DNA can be used to infer their geographic origin with surprising accuracy-often to within a few hundred kilometres.

Phylogeographical structure, postglacial recolonization and barriers to gene flow in the distinctive Valais chromosome race of the common shrew (Sorex araneus).

Using one male-inherited and eight biparentally inherited microsatellite markers, we investigate the population genetic structure of the Valais chromosome race of the common shrew (Sorex araneus) in the Central Alps of Europe. Unexpectedly, the Y-chromosome microsatellite suggests nearly complete absence of male gene flow among populations from the St-Bernard and Simplon regions (Switzerland). Autosomal markers also show significant genetic structuring among these two geographical areas. Isolation by distance is significant and possible barriers to gene flow exist in the study area. Two different approaches are used to better understand the geographical patterns and the causes of this structuring. Using a principal component analysis for which testing procedure exists, and partial Mantel tests, we show that the St-Bernard pass does not represent a significant barrier to gene flow although it culminates at 2469 m, close to the highest altitudinal record for this species. Similar results are found for the Simplon pass, indicating that both passes represented potential postglacial recolonization routes into Switzerland from Italian refugia after the last Pleistocene glaciations. In contrast with the weak effect of these mountain passes, the Rhône valley lowlands significantly reduce gene flow in this species. Natural obstacles (the large Rhône river) and unsuitable habitats (dry slopes) are both present in the valley. Moreover, anthropogenic changes to landscape structures are likely to have strongly reduced available habitats for this shrew in the lowlands, thereby promoting genetic differentiation of populations found on opposite sides of the Rhône valley.