Lack of Association Between the Trp719Arg Polymorphism in Kinesin-Like Protein-6 and Coronary Artery Disease in 19 Case-Control Studies

Objectives: We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455), and clinical coronary artery disease (CAD).
Background: Recent prospective studies suggest that carriers of the 719Arg allele in KIF6 are at increased risk of clinical CAD compared with noncarriers.
Methods: The KIF6 Trp719Arg polymorphism (rs20455) was genotyped in 19 case-control studies of nonfatal CAD either as part of a genome-wide association study or in a formal attempt to replicate the initial positive reports.
Results: A total of 17,000 cases and 39,369 controls of European descent as well as a modest number of South Asians, African Americans, Hispanics, East Asians, and admixed cases and controls were successfully genotyped. None of the 19 studies demonstrated an increased risk of CAD in carriers of the 719Arg allele compared with noncarriers. Regression analyses and fixed-effects meta-analyses ruled out with high degree of confidence an increase of <2% in the risk of CAD among European 719Arg carriers. We also observed no increase in the risk of CAD among 719Arg carriers in the subset of Europeans with early-onset disease (younger than 50 years of age for men and younger than 60 years of age for women) compared with similarly aged controls as well as all non-European subgroups.
Conclusions: The KIF6 Trp719Arg polymorphism was not associated with the risk of clinical CAD in this large replication study.

Hypermobility and musculoskeletal pain in children:a systematic review

Objective: To examine the evidence of an association between hypermobility and musculoskeletal pain in children. Methods: A systematic review of the literature was performed using the databases PubMed, EMBASE, NHS Evidence, and Medline. Inclusion criteria were observational studies investigating hypermobility and musculoskeletal pain in children. Exclusion criteria were studies conducted on specialist groups (i.e. dancers) or hospital referrals. Pooled odds ratios (ORs) were calculated using random effects models and heterogeneity was tested using ?(2)-tests. Study quality was assessed using the Newcastle-Ottawa Scale for case-control studies. Results: Of the 80 studies identified, 15 met the inclusion criteria and were included in the review. Of these, 13 were included in the statistical analyses. Analysing the data showed that the heterogeneity was too high to allow for interpretation of the meta-analysis (I(2) = 72%). Heterogeneity was much lower when the studies were divided into European (I(2) = 8%) and Afro-Asian subgroups (I(2) = 65%). Sensitivity analysis based on data from studies reporting from European and Afro-Asian regions showed no association in the European studies [OR 1.00, 95% confidence interval (CI) 0.79-1.26] but a marked relationship between hypermobility and joint pain in the Afro-Asian group (OR 2.01, 95% CI 1.45-2.77). Meta-regression showed a highly significant difference between subgroups in both meta-analyses (p <0.001). Conclusion: There seems to be no association between hypermobility and joint pain in Europeans. There does seem to be an association in Afro-Asians; however, there was a high heterogeneity. It is unclear whether this is due to differences in ethnicity, nourishment, climate or study design.

Effect of interleukin-6 polymorphisms on human longevity:a systematic review and meta-analysis

Several studies have assessed changes in frequency of -174 interleukin (IL)-6 single nucleotide polymorphism (SNP) with age. If IL-6 tracks with disability and age-related diseases, then there should be reduction, in the oldest old, of the frequency of homozygous GG subjects, who produce higher IL-6 levels. However, discordant results have been obtained. To explore the relationship between this polymorphism and longevity, we analyzed individual data on long-living subjects and controls from eight case-control studies conducted in Europeans, using meta-analysis. There was no significant difference in the IL-6 genotype between the oldest old and controls (Odds Ratio [OR]=0.96; 95% C.I.: 0.77-1.20; p=0.71), but there was significant between-study heterogeneity (I2=55.5%). In a subgroup analyses when male centenarians from the three Italian studies were included, the frequency of the IL-6 -174 GG genotype was significantly lower than the other genotypes (OR=0.49; 95% C.I.: 0.31-0.80; p=0.004), with no evidence of heterogeneity (I2=0%). Our data supports a negative association between the GG genotype of IL-6 SNP and longevity in Italian centenarians, with males who carry the genotype being two times less likely to reach extreme old age compared with subjects carrying CC or CG genotypes. These findings were not replicated in other European groups suggesting a possible interaction between genetics, sex and environment in reaching longevity.

A genome-wide association study of anorexia nervosa

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(^-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

Release of β-galactosidase from poloxamine/α-cyclodextrin hydrogels

All mammals lose their ability to produce lactase (β-galactosidase), the enzyme that cleaves lactose into galactose and glucose, after weaning. The prevalence of lactase deficiency (LD) spans from 2 to 15% among northern Europeans, to nearly 100% among Asians. Following lactose consumption, people with LD often experience gastrointestinal symptoms such as abdominal pain, bowel distension, cramps and flatulence, or even systemic problems such as headache, loss of concentration and muscle pain. These symptoms vary depending on the amount of lactose ingested, type of food and degree of intolerance. Although those affected can avoid the uptake of dairy products, in doing so, they lose a readily available source of calcium and protein. In this work, gels obtained by complexation of Tetronic 90R4 with α-cyclodextrin loaded with β-galactosidase are proposed as a way to administer the enzyme immediately before or with the lactose-containing meal. Both molecules are biocompatible, can form gels in situ, and show sustained erosion kinetics in aqueous media. The complex was characterized by FTIR that evidenced an inclusion complex between the polyethylene oxide block and α-cyclodextrin. The release profiles of β-galactosidase from two different matrices (gels and tablets) of the in situ hydrogels have been obtained. The influence of the percentage of Tetronic in media of different pH was evaluated. No differences were observed regarding the release rate from the gel matrices at pH 6 (t50 = 105 min). However, in the case of the tablets, the kinetics were faster and they released a greater amount of 90R4 (25%, t50 = 40–50 min). Also, the amount of enzyme released was higher for mixtures with 25% Tetronic. Using suitable mathematical models, the corresponding kinetic parameters have been calculated. In all cases, the release data fit quite well to the Peppas–Sahlin model equation, indicating that the release of β-galactosidase is governed by a combination of diffusion and erosion processes. It has been observed that the diffusion mechanism prevails over erosion during the first 50 minutes, followed by continued release of the enzyme due to the disintegration of the matrix.

The Long Aftermath: Cultural Legacies of Europe at War, 1936-2016

In its totality, the “Long Second World War”—extending from the beginning of the Spanish Civil War to the end of hostilities in 1945—has exerted enormous influence over European culture. Bringing together leading historians, sociologists, and literary and film scholars, this broadly interdisciplinary volume investigates Europeans’ individual and collective memories and the ways in which they have shaped the continent’s cultural heritage. Focusing on the major combatant nations—Spain, Britain, France, Italy, Germany, Poland, and Russia—it offers thoroughly contextualized explorations of novels, memoirs, films, and a host of other cultural forms to illuminate European public memory.

Institutional Frameworks and Structural Factors Relating to Educational Access Across Europe

In this article institutional and structural factors relating to access to education are assessed. First, the macro frameworks of institutional regulation that exert influence on the educational trajectories of young Europeans are demonstrated. Based on different aspects of these frameworks and drawing from extant research, the article presents a typology of education systems that provide varying levels of access to and accessibility of education in Finland, France, Germany, Italy, Poland, the Netherlands, Slovenia, and the United Kingdom. Second, using survey data (N = 6,366) it analyzes the impact of gender and parental education on young people’s educational aspirations and early labor-market entry across the countries.

Study of the water consuption of the international tourism sector in the costal zone of southwest Europe

Dissertação de Mestrado, Gestão da Água e da Costa, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2009

Exploring the micro-politics of place: lifestyle migrants, collective identities and modes of belonging

Taking up Hopkins and Dixon’s (2006) call to attend to the micro-politics of everyday constructions of space and place, which necessarily involves psychological concepts such as identity, belonging and attachment, this paper aims to show how a critical socio-cognitive approach to discourse analysis is an effective means of unpacking the ways in which versions of place are (re)produced and negotiated through discursive practices, and in particular the ways in which ‘legitimate’ collective identities are constructed in relation to place. I focus on the contemporary social phenomenon of lifestyle migration. Within Europe, this typically involves relatively affluent northern Europeans moving to destinations in southern Europe that are strongly linked to tourism. Although lifestyle migrants are generally viewed by their hosts as ‘desirable’ migrants due to their perceived economic and socio-cultural capital, their integration into destination communities is often minimal. The question arises as to how these migrants construct modes of belonging in relation to their adopted home-place and how they relate to the other social groups with whom they share it. Using texts from a variety of sources, including in-depth interviews with British migrants in Portugal, I explore not only how migrants position themselves (and others) discursively in relation to places, but also how they are already positioned by discursive practices in the public sphere. I also examine to what extent the construction of a ‘legitimate’ mode of belonging involves the construction of intergroup cooperation within that place.

O expansionismo europeu : os Descobrimentos e a nova visão do mundo nos séculos XV e XVI : uma experiência de ensino

Relatório da Prática de Ensino Supervisionada, Ensino de História e Geografia no 3.º Ciclo do Ensino Básico e Ensino Secundário, Universidade de Lisboa, 2013

Portuguese living standards, 1720-1980, in European comparison: heights, income, and human capital

When and why did the Portuguese become the shortest Europeans? In order to find the answer to this question, we trace the trend in Portuguese living standards from the 1720s until recent times. We find that during the early nineteenth century average height in Portugal did not differ significantly from average height in most other European countries, but that when, around 1850, European anthropometric values began to climb sharply, Portugal's did not. In a panel analysis of 12 countries, we find that delay in human-capital formation was the chief factor hindering any improvement in the biological standard of living in Portugal.

Fostering e-participation sustainability through a BPM-driven semantic model

According to a recent Eurobarometer survey (2014), 68% of Europeans tend not to trust national governments. As the increasing alienation of citizens from politics endangers democracy and welfare, governments, practitioners and researchers look for innovative means to engage citizens in policy matters. One of the measures intended to overcome the so-called democratic deficit is the promotion of civic participation. Digital media proliferation offers a set of novel characteristics related to interactivity, ubiquitous connectivity, social networking and inclusiveness that enable new forms of societal-wide collaboration with a potential impact on leveraging participative democracy. Following this trend, e-Participation is an emerging research area that consists in the use of Information and Communication Technologies to mediate and transform the relations among citizens and governments towards increasing citizens’ participation in public decision-making. However, despite the widespread efforts to implement e-Participation through research programs, new technologies and projects, exhaustive studies on the achieved outcomes reveal that it has not yet been successfully incorporated in institutional politics. Given the problems underlying e-Participation implementation, the present research suggested that, rather than project-oriented efforts, the cornerstone for successfully implementing e-Participation in public institutions as a sustainable added-value activity is a systematic organisational planning, embodying the principles of open-governance and open-engagement. It further suggested that BPM, as a management discipline, can act as a catalyst to enable the desired transformations towards value creation throughout the policy-making cycle, including political, organisational and, ultimately, citizen value. Following these findings, the primary objective of this research was to provide an instrumental model to foster e-Participation sustainability across Government and Public Administration towards a participatory, inclusive, collaborative and deliberative democracy. The developed artefact, consisting in an e-Participation Organisational Semantic Model (ePOSM) underpinned by a BPM-steered approach, introduces this vision. This approach to e-Participation was modelled through a semi-formal lightweight ontology stack structured in four sub-ontologies, namely e-Participation Strategy, Organisational Units, Functions and Roles. The ePOSM facilitates e-Participation sustainability by: (1) Promoting a common and cross-functional understanding of the concepts underlying e-Participation implementation and of their articulation that bridges the gap between technical and non-technical users; (2) Providing an organisational model which allows a centralised and consistent roll-out of strategy-driven e-Participation initiatives, supported by operational units dedicated to the execution of transformation projects and participatory processes; (3) Providing a standardised organisational structure, goals, functions and roles related to e-Participation processes that enhances process-level interoperability among government agencies; (4) Providing a representation usable in software development for business processes’ automation, which allows advanced querying using a reasoner or inference engine to retrieve concrete and specific information about the e-Participation processes in place. An evaluation of the achieved outcomes, as well a comparative analysis with existent models, suggested that this innovative approach tackling the organisational planning dimension can constitute a stepping stone to harness e-Participation value.

Reforms of the pre-graduate curriculum for medical students: the Bologna process and beyond.

For several years, all five medical faculties of Switzerland have embarked on a reform of their training curricula for two reasons: first, according to a new federal act issued in 2006 by the administration of the confederation, faculties needed to meet international standards in terms of content and pedagogic approaches; second, all Swiss universities and thus all medical faculties had to adapt the structure of their curriculum to the frame and principles which govern the Bologna process. This process is the result of the Bologna Declaration of June 1999 which proposes and requires a series of reforms to make European Higher Education more compatible and comparable, more competitive and more attractive for Europeans students. The present paper reviews some of the results achieved in the field, focusing on several issues such as the shortage of physicians and primary care practitioners, the importance of public health, community medicine and medical humanities, and the implementation of new training approaches including e-learning and simulation. In the future, faculties should work on several specific challenges such as: students' mobility, the improvement of students' autonomy and critical thinking as well as their generic and specific skills and finally a reflection on how to improve the attractiveness of the academic career, for physicians of both sexes.

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.

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.