Pathology as the Cornerstone of Human Tissue Banking: European Consensus Expert Group Report

Aside from ethical considerations, the primary requirement for usage of human tissues in basic or translational research is the thorough characterization of tissues. The second, but equally essential, requirement is that tissues be collected, processed, annotated, and preserved in optimal conditions. These requirements put the pathologist at the center of tissue banking activities and of research aimed at discovering new biomarkers. Pathologists not only provide information identifying the specimen but also make decisions on what materials should be biobanked, on the preservation conditions, and on the timeline of events that precede preservation and storage. This central position calls for increased recognition of the role of the pathologist by the biomolecular community and places new demands on the pathologist's workload and scope of scientific activities. These questions were addressed by an Expert Group Meeting of the European Biological and Biomolecular Research Infrastructure (BBMRI). While detailed recommendations are published elsewhere (Bevilacqua et al., Virchows Archivs, 2010, in press), this article outlines the strategic and technological issues identified by the Expert Group and identifies ways forward for better integration of pathology in the current thrust for development of biomarker-based "personalized medicine.

Linkages of dietary patterns, international trade and land use: the case of olive oil in the European Union

Within only two decades olive oil developed from a niche product which could hardly be found in food stores outside the producing regions towards an integrated component in the diets of industrial countries. This paper discusses the impacts of the promotion of the “healthy Mediterranean diet” on land use and agro-ecosystems in the producing countries. It examines the dynamics of olive oil production, trade and consumption in the EU15 in the period 1972 to 2003 and the links between dietary patterns, trade and land use. It analyses the underlying socio-economic driving forces behind the increasing spatial disconnect between production and consumption of olive oil in the EU15 and in particular in Spain, the world largest producer during the last three decades. In the observed period olive oil consumption increased 16 fold in the non-producing EU15 countries. In the geographically limited producing regions like Spain, the 5 fold increase in export production was associated with the rapid industrialization of olive production, the conversion of vast Mediterranean landscapes to olive monocultures and a range of environmental pressures. High amounts of subsidies of the European Common Agricultural Policy and feedback loops within production and consumption systems were driving the transformation of the olive oil system. Our analysis indicates the process of change was not immediately driven by increases in demand for olive oil in non-producing countries, but rather by the institutional setting of the European Union and by concerted political interventions.

Overuse and underuse of colonoscopy in a European primary care setting.

BACKGROUND: Efforts to decrease overuse of health care may result in underuse. Overuse and underuse of colonoscopy have never been simultaneously evaluated in the same patient population. METHODS: In this prospective observational study, the appropriateness and necessity of referral for colonoscopy were evaluated by using explicit criteria developed by a standardized expert panel method. Inappropriate referrals constituted overuse. Patients with necessary colonoscopy indications who were not referred constituted underuse. Consecutive ambulatory patients with lower gastrointestinal (GI) symptoms from 22 general practices in Switzerland, a country with ready access to colonoscopy, were enrolled during a 4-week period. Follow-up data were obtained at 3 months for patients who did not undergo a necessary colonoscopy. RESULTS: Eight thousand seven hundred sixty patient visits were screened for inclusion; 651 patients (7.4%) had lower GI symptoms (mean age 56.4 years, 68% women). Of these, 78 (12%) were referred for colonoscopy. Indications for colonoscopy in 11 patients (14% of colonoscopy referrals or 1.7% of all patients with lower GI symptoms) were judged inappropriate. Among 573 patients not referred for the procedure, underuse ranged between 11% and 28% of all patients with lower GI symptoms, depending on the criteria used. CONCLUSIONS: Applying criteria from an expert panel of nationally recognized experts indicates that underuse of referral for colonoscopy exceeds overuse in primary care in Switzerland. To improve quality of care, both overuse and underuse of important procedures must be addressed.

SYSGENET: a meeting report from a new European network for systems genetics.

The first scientific meeting of the newly established European SYSGENET network took place at the Helmholtz Centre for Infection Research (HZI) in Braunschweig, April 7-9, 2010. About 50 researchers working in the field of systems genetics using mouse genetic reference populations (GRP) participated in the meeting and exchanged their results, phenotyping approaches, and data analysis tools for studying systems genetics. In addition, the future of GRP resources and phenotyping in Europe was discussed.

Superinfection with drug-resistant HIV is rare and does not contribute substantially to therapy failure in a large European cohort.

BACKGROUND: Superinfection with drug resistant HIV strains could potentially contribute to compromised therapy in patients initially infected with drug-sensitive virus and receiving antiretroviral therapy. To investigate the importance of this potential route to drug resistance, we developed a bioinformatics pipeline to detect superinfection from routinely collected genotyping data, and assessed whether superinfection contributed to increased drug resistance in a large European cohort of viremic, drug treated patients. METHODS: We used sequence data from routine genotypic tests spanning the protease and partial reverse transcriptase regions in the Virolab and EuResist databases that collated data from five European countries. Superinfection was indicated when sequences of a patient failed to cluster together in phylogenetic trees constructed with selected sets of control sequences. A subset of the indicated cases was validated by re-sequencing pol and env regions from the original samples. RESULTS: 4425 patients had at least two sequences in the database, with a total of 13816 distinct sequence entries (of which 86% belonged to subtype B). We identified 107 patients with phylogenetic evidence for superinfection. In 14 of these cases, we analyzed newly amplified sequences from the original samples for validation purposes: only 2 cases were verified as superinfections in the repeated analyses, the other 12 cases turned out to involve sample or sequence misidentification. Resistance to drugs used at the time of strain replacement did not change in these two patients. A third case could not be validated by re-sequencing, but was supported as superinfection by an intermediate sequence with high degenerate base pair count within the time frame of strain switching. Drug resistance increased in this single patient. CONCLUSIONS: Routine genotyping data are informative for the detection of HIV superinfection; however, most cases of non-monophyletic clustering in patient phylogenies arise from sample or sequence mix-up rather than from superinfection, which emphasizes the importance of validation. Non-transient superinfection was rare in our mainly treatment experienced cohort, and we found a single case of possible transmitted drug resistance by this route. We therefore conclude that in our large cohort, superinfection with drug resistant HIV did not compromise the efficiency of antiretroviral treatment.

Implementation of IPM programs on European greenhouse tomato production areas: Tools and constraints

Whiteflies and whitefly-transmitted viruses are some of the major constraints on European tomato production. The main objectives of this study were to: identify where and why whiteflies are a major limitation on tomato crops; collect information about whiteflies and associated viruses; determine the available management tools; and identify key knowledge gaps and research priorities. This study was conducted within the framework of ENDURE (European Network for Durable Exploitation of Crop Protection Strategies). Two whitefly species are the main pests of tomato in Europe: Bemisia tabaci and Trialeurodes vaporariorum. Trialeurodes vaporariorum is widespread to all areas where greenhouse industry is present, and B. tabaci has invaded, since the early 1990’s, all the subtropical and tropical areas. Biotypes B and Q of B. tabaci are widespread and especially problematic. Other key tomato pests are Aculops lycopersici, Helicoverpa armigera, Frankliniella occidentalis, and leaf miners. Tomato crops are particularly susceptible to viruses causingTomato yellow leaf curl disease (TYLCD). High incidences of this disease are associated to high pressure of its vector, B. tabaci. The ranked importance of B. tabaci established in this study correlates with the levels of insecticide use, showing B. tabaci as one of the principal drivers behind chemical control. Confirmed cases of resistance to almost all insecticides have been reported. Integrated Pest Management based on biological control (IPM-BC) is applied in all the surveyed regions and identified as the strategy using fewer insecticides. Other IPM components include greenhouse netting and TYLCD-tolerant tomato cultivars. Sampling techniques differ between regions, where decisions are generally based upon whitefly densities and do not relate to control strategies or growing cycles. For population monitoring and control, whitefly species are always identified. In Europe IPM-BC is the recommended strategy for a sustainable tomato production. The IPM-BC approach is mainly based on inoculative releases of the parasitoids Eretmocerus mundus and Encarsia formosa and/or the polyphagous predators Macrolophus caliginosus and Nesidiocoris tenuis. However, some limitations for a wider implementation have been identified: lack of biological solutions for some pests, costs of beneficials, low farmer confidence, costs of technical advice, and low pest injury thresholds. Research priorities to promote and improve IPM-BC are proposed on the following domains: (i) emergence and invasion of new whitefly-transmitted viruses; (ii) relevance of B. tabaci biotypes regarding insecticide resistance; (iii) biochemistry and genetics of plant resistance; (iv) economic thresholds and sampling techniques of whiteflies for decision making; and (v) conservation and management of native whitefly natural enemies and improvement of biological control of other tomato pests.

Cost evaluation of cardiovascular magnetic resonance versus coronary angiography for the diagnostic work-up of coronary artery disease: Application of the European Cardiovascular Magnetic Resonance registry data to the German, United Kingdom, Swiss, and United States health care systems.

ABSTRACT: BACKGROUND: Cardiovascular magnetic resonance (CMR) has favorable characteristics for diagnostic evaluation and risk stratification of patients with known or suspected CAD. CMR utilization in CAD detection is growing fast. However, data on its cost-effectiveness are scarce. The goal of this study is to compare the costs of two strategies for detection of significant coronary artery stenoses in patients with suspected coronary artery disease (CAD): 1) Performing CMR first to assess myocardial ischemia and/or infarct scar before referring positive patients (defined as presence of ischemia and/or infarct scar to coronary angiography (CXA) versus 2) a hypothetical CXA performed in all patients as a single test to detect CAD. METHODS: A subgroup of the European CMR pilot registry was used including 2,717 consecutive patients who underwent stress-CMR. From these patients, 21% were positive for CAD (ischemia and/or infarct scar), 73% negative, and 6% uncertain and underwent additional testing. The diagnostic costs were evaluated using invoicing costs of each test performed. Costs analysis was performed from a health care payer perspective in German, United Kingdom, Swiss, and United States health care settings. RESULTS: In the public sectors of the German, United Kingdom, and Swiss health care systems, cost savings from the CMR-driven strategy were 50%, 25% and 23%, respectively, versus outpatient CXA. If CXA was carried out as an inpatient procedure, cost savings were 46%, 50% and 48%, respectively. In the United States context, cost savings were 51% when compared with inpatient CXA, but higher for CMR by 8% versus outpatient CXA. CONCLUSION: This analysis suggests that from an economic perspective, the use of CMR should be encouraged as a management option for patients with suspected CAD.

Recerca versus docència en una experiència d'internalització dels estudis de Geografia a la Universitat de Girona: The faces of landscape, Catalonia and North Karelia = Research versus teaching in one experience of internationalization of the Geography degree studies in the University of Girona: The faces of landscape, Catalonia and North Karelia

Un dels reptes cabdals de la Universitat és enllaçar l’experiència de recerca amb la docència, així com promoure la internacionalització dels estudis, especialment a escala europea, tenint present que ambdues poden actuar com a catalitzadores de la millora de la qualitat docent. Una de les fórmules d’internacionalització és la realització d’assignatures compartides entre universitats de diferents països, fet que suposa l’oportunitat d’implementar noves metodologies docents. En aquesta comunicació es presenta una experiència en aquesta línia desenvolupada entre la Universitat de Girona i la Universitat de Joensuu (Finlàndia) en el marc dels estudis de Geografia amb la realització de l’assignatura 'The faces of landscape: Catalonia and North Karelia'. Aquesta es desenvolupa al llarg de dues setmanes intensives, una en cadascuna de les Universitats. L’objectiu és presentar i analitzar diferents significats del concepte paisatge aportant també metodologies d’estudi tant dels aspectes físics i ecològics com culturals que s’hi poden vincular i que són les que empren els grups de recerca dels professors responsables de l’assignatura. Aquesta part teòrica es completa amb una presentació de les característiques i dinàmiques pròpies dels paisatges finlandesos i catalans i una sortida de camp. Per a la part pràctica es constitueixen grups d’estudi multinacionals que treballen a escala local algun dels aspectes en els dos països, es comparen i es realitza una presentació i defensa davant del conjunt d’estudiants i professorat. La llengua vehicular de l’assignatura és l’anglès.

The value of selected in vitro and in silico methods to predict acute oral toxicity in a regulatory context: results from the European Project ACuteTox.

ACuteTox is a project within the 6th European Framework Programme which had as one of its goals to develop, optimise and prevalidate a non-animal testing strategy for predicting human acute oral toxicity. In its last 6 months, a challenging exercise was conducted to assess the predictive capacity of the developed testing strategies and final identification of the most promising ones. Thirty-two chemicals were tested blind in the battery of in vitro and in silico methods selected during the first phase of the project. This paper describes the classification approaches studied: single step procedures and two step tiered testing strategies. In summary, four in vitro testing strategies were proposed as best performing in terms of predictive capacity with respect to the European acute oral toxicity classification. In addition, a heuristic testing strategy is suggested that combines the prediction results gained from the neutral red uptake assay performed in 3T3 cells, with information on neurotoxicity alerts identified by the primary rat brain aggregates test method. Octanol-water partition coefficients and in silico prediction of intestinal absorption and blood-brain barrier passage are also considered. This approach allows to reduce the number of chemicals wrongly predicted as not classified (LD50>2000 mg/kg b.w.).

Modelling the distribution of bats in relation to landscape structure in a temperate mountain environment

1. Landscape modification is often considered the principal cause of population decline in many bat species. Thus, schemes for bat conservation rely heavily on knowledge about species-landscape relationships. So far, however, few studies have quantified the possible influence of landscape structure on large-scale spatial patterns in bat communities. 2. This study presents quantitative models that use landscape structure to predict (i) spatial patterns in overall community composition and (ii) individual species' distributions through canonical correspondence analysis and generalized linear models, respectively. A geographical information system (GIS) was then used to draw up maps of (i) overall community patterns and (ii) distribution of potential species' habitats. These models relied on field data from the Swiss Jura mountains. 3. Fight descriptors of landscape structure accounted for 30% of the variation in bat community composition. For some species, more than 60% of the variance in distribution could be explained by landscape structure. Elevation, forest or woodland cover, lakes and suburbs, were the most frequent predictors. 4. This study shows that community composition in bats is related to landscape structure through species-specific relationships to resources. Due to their nocturnal activities and the difficulties of remote identification, a comprehensive bat census is rarely possible, and we suggest that predictive modelling of the type described here provides an indispensable conservation tool.

Landscape genetics of the Alpine newt (Mesotriton alpestris) inferred from a strip-based approach

Habitat destruction and fragmentation are known to strongly affect dispersal by altering the quality of the environment between populations. As a consequence, lower landscape connectivity is expected to enhance extinction risks through a decrease in gene flow and the resulting negative effects of genetic drift, accumulation of deleterious mutations and inbreeding depression. Such phenomena are particularly harmful for amphibian species, characterized by disjunct breeding habitats. The dispersal behaviour of amphibians being poorly understood, it is crucial to develop new tools, allowing us to determine the influence of landscape connectivity on the persistence of populations. In this study, we developed a new landscape genetics approach that aims at identifying land-uses affecting genetic differentiation, without a priori assumptions about associated ecological costs. We surveyed genetic variation at seven microsatellite loci for 19 Alpine newt (Mesotriton alpestris) populations in western Switzerland. Using strips of varying widths that define a dispersal corridor between pairs of populations, we were able to identify land-uses that act as dispersal barriers (i.e. urban areas) and corridors (i.e. forests). Our results suggest that habitat destruction and landscape fragmentation might in the near future affect common species such as M. alpestris. In addition, by identifying relevant landscape variables influencing population structure without unrealistic assumptions about dispersal, our method offers a simple and flexible tool of investigation as an alternative to least-cost models and other approaches.

Cross-country polarisation in CO2 emissions per capita in the European Union: changes and explanatory factors

In this study, we analyse the degree of polarisation-a concept fundamentally different from that of inequality-in the international distribution of CO2 emissions per capita in the European Union. It is analytically relevant to examine the degree of instability inherent to a distribution and, in the analysed case, the likelihood that the distribution and its evolution will increase or decrease the chances of reaching an agreement. Two approaches were used to measure polarisation: the endogenous approach, in which countries are grouped according to their similarity in terms of emissions, and the exogenous approach, in which countries are grouped geographically. Our findings indicate a clear decrease in polarisation since the mid-1990s, which can essentially be explained by the fact that the different groups of countries have converged (i.e. antagonism among the CO2 emitters has decreased) as the contribution of energy intensity to between-group differences has decreased. This lower degree of polarisation in CO2 distribution suggests a situation more conducive to the possibility of reaching EU-wide agreements on the mitigation of CO2 emissions.

Explanatory factors of CO2 per capita emission inequality in the European Union

The design of European mitigation policies requires a detailed examination of the factors explaining the unequal emissions in the different countries. This research analyzes the evolution of inequality in CO2 per capita emissions in the European Union (EU-27) in the 1990-2006 period and its explanatory factors. For this purpose, we decompose the Theil index of inequality into the contributions of the different Kaya factors. The decomposition is also applied to the inequality between and within groups of countries (North Europe, South Europe, and East Europe). The analysis shows an important reduction in inequality, to a large extent due to the smaller differences between groups and because of the lower contribution of the energy intensity factor. The importance of the GDP per capita factor increases and becomes the main explanatory factor. However, within the different groups of countries the carbonization index appears to be the most relevant factor in explaining inequalities.