And We’d Like to Thank…::Romania’s Integration into the European Union, 1989-2007

Conditionality is formally a key determinant of many non-member states’ relations with the EU. It is particularly so for states intent on membership. As the case of Romania shows, the EU’s use of conditionality is far from consistent. Relations can develop and accession take place without the requisite conditions being met. This follows from the use the EU makes of the flexibility evident in its evolving and generally vague definitions of the conditions that need to be met. Hence it was often extraneous factors over which Romania had either limited or no influence that were responsible for key developments in relations. These factors include the geopolitical and strategic interests of the EU and its member states, the actions of the Commission and the agenda-setting and constraining effects of rhetorical commitments and timetables, and the dynamics of the EU’s evolving approach to eastern enlargement.

Patterns of variation at a mitochondrial sequence-tagged-site locus provides new insights into the postglacial history of European Pinus sylvestris populations

Due to their maternal mode of inheritance, mitochondrial markers can be regarded as almost 'ideal' tools in evolutionary studies of conifer populations. In the present study, polymorphism was analysed at one mitochondrial intron (nad 1, exon B/C) in 23 native European Pinus sylvestris populations. In a preliminary screening for variation using a polymerase chain reaction-restriction fragment length polymorphism approach, two length variants were identified. By fully sequencing the 2.5 kb region, the observed length polymorphism was found to result from the insertion of a 31 bp sequence, with no other mutations observed within the intron. A set of primers was designed flanking the observed mutation, which identified a novel sequence-tagged-site mitochondrial marker for P. sylvestris. Analysis of 747 trees from the 23 populations using these primers revealed the occurrence of two distinct haplotypes in Europe. Within the Iberian Peninsula, the two haplotypes exhibited extensive population differentiation (Phi(ST) = 0.59; P less than or equal to 0.001) and a marked geographical structuring. In the populations of central and northern Europe, one haplotype largely predominated, with the second being found in only one individual of one population.

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.

Wealth concentration in the European periphery: Ireland, 1858–2001

Using annual will indexes, a series of wealth concentration is constructed for the north of Ireland on a decennial basis for the period 1858 to 2001. Wealth was highly concentrated at the beginning of the sample period, but inequality falls towards the end of the nineteenth century and continues to fall until the 1970s. However, there does not appear to be a Kuznets-type process at work. Instead, using data on socio-occupational status, it is suggested that the fall in wealth concentration appears to be associated with the demise of the titled classes. Interestingly, similar to the findings of other studies, wealth has become more concentrated since the 1970s.

An Ecological Correlation Study of Late Age-Related Macular Degeneration and the Complement Factor H Y402H Polymorphism

PURPOSE:
To investigate whether variation in the distribution of the risk allele frequency of the Y402H single-nucleotide polymorphism (SNP) across various ethnicities and geographic regions reflects differences in the prevalence of late age-related macular degeneration (AMD) in those ethnicities.

METHODS:
Published data were obtained via a systematic search. Study samples were grouped into clusters by ethnicity and geographic location and the Spearman correlation coefficient of the prevalence of late AMD and risk allele frequencies was calculated across clusters.

RESULTS:
Across all ethnicities, AMD prevalence was seen to increase with age. Populations of European descent had both higher risk allele frequencies and prevalence of late AMD than did Japanese, Chinese, and Hispanic descendants. Results for African descendants were anomalous: although allele frequency was similar to that in European populations, the age-specific prevalence of late AMD was considerably lower. The correlation coefficient for the association between allele frequency and AMD prevalence was 0.40 (95% confidence interval [CI] = -0.36 to 0.84, P = 0.28) in all populations combined and 0.71 (95% CI = 0.02-0.94, P = 0.04) when people of African descent were excluded.

CONCLUSIONS:
Evidence was found at the population level to support a positive association between the Y204H risk allele and the prevalence of AMD after exclusion of studies undertaken on persons of African ancestry. Data in African, Middle Eastern, and South American populations are needed to provide a better understanding of the association of late AMD genetic risk across ethnicities.

The genetics of coronary heart disease: The contribution of twin studies

Despite the decline in coronary heart disease in many European countries, the disease remains an enormous public health problem. Although we know a great deal about environmental risk factors for coronary heart disease, a heritable component was recognized a long time ago. The earliest and best known examples of how our genetic constitution may determine cardiovascular risk relate to lipoprotein(a), familial hypercholesterolaemia and apolipoprotein E. In the past 20 years a fair number of polymorphisms assessed singly have shown strong associations with the disease but most are subject to poor repeatability. Twins constitute a compelling natural experiment to establish the genetic contribution to coronary heart disease and its risk factors. GenomEUtwin, a recently funded Framework 5 Programme of the European Community, affords the opportunity of comparing the heritability of risk factors in different European Twin Registries. As an illustration we present the heritabilities of systolic and diastolic blood pressure, based on data from over 4000 twin pairs from six different European countries and Australia. Heritabilities for systolic blood pressure are between 52 and 66% and for diastolic blood pressure between 44 and 66%. There is no evidence of sex differences in heritability estimates and very little to no evidence for a significant contribution of shared family environment. A non-twin based prospective case/cohort study of coronary heart disease and stroke (MORGAM) will allow hypotheses relating to cardiovascular disease, generated in the twin cohorts, to be tested prospectively in adult populations. Twin studies have also contributed to our understanding of the life course hypothesis, and GenomEUtwin has the potential to add to this.

A fish bradykinin (Arg0; Trp5; Leu8-bradykinin) from the defensive skin secretion of the European edible frog; Pelophylax kl. esculentus: structural characterization; molecular cloning of skin kininogen cDNA and pharmacological effects on mammalian smooth muscle

Extensive studies on bradykinin-related peptides (BRPs) generated from plasma kininogens in representative species of various vertebrate taxa, have confirmed that many amphibian skin BRPs reflect those present in putative vertebrate predators. For example, the (Val1, Thr6)-bradykinin, present in the defensive skin secretions of many ranids and phyllomedusines, can be generated from plasma kininogens in colubrid snakes - common predators of these frogs. Here, we report the presence of (Arg0, Trp5, Leu8)-bradykinin in the skin secretion of the European edible frog, Pelophylax kl. esculentus, and have found it to be encoded in single copy by a kininogen with an open-reading frame of 68 amino acid residues. This peptide is the archetypal bony fish bradykinin that has been generated from plasma kininogens of the bowfin (Amia calva), the long-nosed gar (Lepisosteus oseus) and the rainbow trout (Onchorhynchus mykiss). More recently, this peptide has been shown to be encoded within cloned kininogens of the Atlantic cod (Gadus morhua) spotted wolf-fish (Anarichas minor), zebrafish (Danio rerio), pufferfish (Tetraodon nigroviridis) and Northern pike (Esox lucius). The latter species is regarded as a major predator of P. kl. esculentus. Synthetic (Arg0, Trp5, Leu8)-bradykinin was previously reported as having multiphasic effects on arterial blood pressure in conscious trout and here we have demonstrated that it can antagonize the relaxation in rat arterial smooth muscle induced by canonical mammalian bradykinin. The discovery of (Arg0, Trp5, Leu8)-bradykinin in the defensive skin secretion of this amphibian completes the spectrum of vertebrate taxon-specific BRPs identified from this source.