Evidence from northwest European bogs shows 'Little Ice Age' climatic changes driven by variations in solar activity

Fluctuations in Holocene atmospheric radiocarbon concentrations have been shown to be due to variations in solar activity. Analyses of both Be-10 and C-14 nuclides confirm that production-rate changes during the Holocene were largely modulated by solar activity. Analyses of peat samples from two intact European ombrotrophic bogs show that climatic deteriorations during the 'Little Ice Age' are associated with transitions to increasing atmospheric C-14 content due to greater C-14 production. Both ombrotrophic mires, which are positioned c. 800 km apart, register reactions to globally recorded C-14 fluctuations between AD 1449 and 1464 and an almost identical reaction between AD 1601 and 1604.

Antimicrobial peptides in the venom of the European hornet, Vespa crabro, identified as mastoparan C and crabrolin

Amphibian skin secretions are rich sources of cationic amphipathic peptides which often possess potent and broad-spectrum antimicrobial activity. However, the venoms of other animals such as hymenopteran insects, also contain peptides with these characteristics and the literature is unclear as to their antimicrobial potential. Here we subjected the venom of the European hornet, Vespa crabro, to reverse phase HPLC fractionation followed by screening of aliquots of individual fractions in bacterial zonal inhibition assays. Two major peptides possessing activity in these assays were further purified by HPLC and subjected to MALDI-TOF MS analysis and MS/MS fragmentation using an ESI mass spectrometer. The peptides were identified as mastoparan C (LNLKALLAVAKKILamide) and crabrolin (FLPLILRKIVTALamide). Replicates of both peptides were synthesised by solid-phase methodology and mean inhibitory concentrations (MICs) established against Staphylococcus aureus and Escherichia coli. Mastoparan C was found to be a potent antimicrobial with MIC values of 2 µM and 4 µM against S. aureus and E. coli, respectively. Crabrolin was found to be less potent with MIC values of > 160 µM and 40 µM for S. aureus and E. coli. Hornet venom thus contains a potent antimicrobial peptide that has been unambiguously identified as mastoparan C, a peptide that is known to affect profound histamine release from mast cells and to generally activate membrane G protein-linked receptors. It is thus highly probable that its antimicrobial effects, like those previously documented, are a result of a generalized membrane interactive and disruptive function — perhaps reflective of the authentic role of amphibian skin antimicrobials.

Disparities in breast cancer mortality trends between 30 European countries: Retrospective trend analysis of WHO mortality database

Objective: To examine changes in temporal trends in breast cancer mortality in women living in 30 European countries.
Design: Retrospective trend analysis.
Data source: WHO mortality database on causes of deaths
Subjects reviewed: Female deaths from breast cancer from 1989 to 2006
Main outcome measures: Changes in breast cancer mortality for all women and by age group (<50, 50-69, and >= 70 years) calculated from linear regressions of log transformed, age adjusted death rates. Joinpoint analysis was used to identify the year when trends in all age mortality began to change.
Results: From 1989 to 2006, there was a median reduction in breast cancer mortality of 19%, ranging from a 45% reduction in Iceland to a 17% increase in Romania. Breast cancer mortality decreased by >= 20% in 15 countries, and the reduction tended to be greater in countries with higher mortality in 1987-9. England and Wales, Northern Ireland, and Scotland had the second, third, and fourth largest decreases of 35%, 29%, and 30%, respectively. In France, Finland, and Sweden, mortality decreased by 11%, 12%, and 16%, respectively. In central European countries mortality did not decline or even increased during the period. Downward mortality trends usually started between 1988 and 1996, and the persistent reduction from 1999 to 2006 indicates that these trends may continue. The median changes in the age groups were -37% (range -76% to -14%) in women aged <50, -21% (-40% to 14%) in 50-69 year olds, and -2% (-42% to 80%) in >= 70 year olds.
Conclusions: Changes in breast cancer mortality after 1988 varied widely between European countries, and the UK is among the countries with the largest reductions. Women aged <50 years showed the greatest reductions in mortality, also in countries where screening at that age is uncommon. The increasing mortality in some central European countries reflects avoidable mortality.

European development of clofarabine as treatment for older patients with acute myeloid leukemia considered unsuitable for intensive chemotherapy.

PURPOSE:
Treatment options for older patients with acute myeloid leukemia (AML) who are not considered suitable for intensive chemotherapy are limited. We assessed the second-generation purine nucleoside analog, clofarabine, in two similar phase II studies in this group of patients.
PATIENTS AND METHODS:
Two consecutive studies, UWCM-001 and BIOV-121, recruited untreated older patients with AML to receive up to four or six 5-day courses of clofarabine. Patients in UWCM-001 were either older than 70 years or 60 to 69 years of age with poor performance status (WHO > 2) or with cardiac comorbidity. Patients in BIOV-121 were >or= 65 years of age and deemed unsuitable for intensive chemotherapy.
RESULTS:
A total of 106 patients were treated in the two monotherapy studies. Median age was 71 years (range, 60 to 84 years), 30% had adverse-risk cytogenetics, and 36% had a WHO performance score >or= 2. Forty-eight percent had a complete response (32% complete remission, 16% complete remission with incomplete peripheral blood count recovery), and 18% died within 30 days. Interestingly, response and overall survival were not inferior in the adverse cytogenetic risk group. The safety profile of clofarabine in these elderly patients with AML who were unsuitable for intensive chemotherapy was manageable and typical of a cytotoxic agent in patients with acute leukemia. Patients had similar prognostic characteristics to matched patients treated with low-dose cytarabine in the United Kingdom AML14 trial, but had significantly superior response and overall survival.
CONCLUSION:
Clofarabine is active and generally well tolerated in this patient group. It is worthy of further evaluation in comparative trials and might be of particular use in patients with adverse cytogenetics.

‘‘Capital of Culture - you must be having a laugh!” Challenging the official rhetoric of Liverpool as the 2008 European cultural capital’

Major cultural events are increasingly seen by local stakeholders as important opportunities to stimulate urban regeneration, city branding and economic development. The European Capital of Culture programme is a prominent example. Since 1985 over thirty cities have hosted the title and today it remains a highly sought-after prize. This paper analyses competing interpretations of the success of Liverpool's hosting of the European Capital of Culture in 2008. It unpacks contrasting views of Liverpool08, from the official triumphant message of urban regeneration and economic renaissance to more critical analyses that problematise important elements of the event and its social and spatial impacts. In so doing, it challenges the hyperbole of culture-led transformation to reveal different geographies of culture, different cultural experiences and different socio-economic realities; it also offers an additional cultural reading of Liverpool in 2008. Through the example of Liverpool this paper shows how local culture is politicised, manipulated and sanitised in order to stimulate urban regeneration and construct a spatial re-branding of the city.

De grands événements culturels sont de plus en plus perçus par les rentiers locaux comme des opportunités importantes pour stimuler la régénération urbaine, produire la devise des villes et le développement économique. L'initiative La Capitale Européenne de la Culture est un exemple proéminent. Depuis 1985, plus de trente villes ont accueilli le titre et maintenant il reste un prix largement recherché. Cet article analyse des interprétations en concurrence du succès de l'accueil de Liverpool de la Capitale Européenne de la Culture en 2008. Il déballe des vues contrastées de Liverpool08, du message officiel et triomphal de la régénération urbaine et de la renaissance économique à des analyses plus critiques qui problématisent des éléments importants de l'événement et ses impacts sociaux et spatiaux. De cette façon, il conteste l'hyperbole de la transformation menée par la culture pour révéler des géographies différentes de la culture, des expériences différentes de la culture et des réalités socioéconomiques différentes; il offre aussi une interprétation culturelle différente de Liverpool en 2008. Au travers de l'exemple de Liverpool cet article montre comment la culture locale est politisée, manipulée et aseptisée pour stimuler la régénération urbaine et construire un relookage spatial de la ville.

Cada vez más, los inversores locales vean a los eventos culturales como oportunidades importantes para estimular regeneración urbana, el desarollo económico y la branding a una ciudad. El Capital Europeo de Cultura es un ejemplo prominente. Desde 1985, más que treinta ciudades han presentado el título y hoy sigue siendo un premio deseable. Este papel se analiza interpretaciones competitivos del éxito del Capital Europea de Cultura 2008 en Liverpool. Se deshace las perspectivas opuestas del Liverpool08, del mensaje triunfante de regeneración urbana y renacimiento económico, a analices críticos que problematizan elementos importantes del evento y sus impactos sociales y espaciales. Al hacer esto, se cuestiona el hipérbole de la transformación cultural para revelar geografías diferentes de cultura, experiencias culturales diferentes y realidades diferentes socio-económicas; también ofrece un entendimiento cultural adicional de Liverpool en el 2008. Através el ejemplo de Liverpool, este papel demuestra como la cultura local está politizada, manipulada, y desinfectado para estimular regeneración urbana y construir una nueva branding de la ciudad.