New stakeholders, spaces and instruments of analysis in the context of energy relationships: Case studies from Kazakhstan and Turkmenistan

The disintegration of the USSR brought the emergence of a new geo-energy space in Central Asia. This space arose in the context of a global energy transition, which began in the late 1970s. Therefore, this new space in a changing energy world requires both new conceptual frameworks of analysis and the creation of new analytical tools. Taking into account this fact, our paper attempts to apply the theoretical framework of the Global Commodity Chain (GCC) to the case of natural resources in Central Asia. The aim of the paper is to check if there could be any Central Asia’s geo-energy space, assuming that this space would exist if natural resources were managed with regional criteria. The paper is divided into four sections. First an introduction that describes the new global energy context within natural resources of Central Asia would be integrated. Secondly, the paper justifies why the GCC methodology is suitable for the study of the value chains of energy products. Thirdly, we build up three cases studies (oil and uranium from Kazakhstan and gas from Turkmenistan) which reveal a high degree of uncertainty over the direction these chains will take. Finally, we present the conclusions of this study that state that the most plausible scenario would be the integration of energy resources of these countries in GCC where the core of the decision-making process will be far away from the region of Central Asia. Key words: Energy transition, geo-energy space, Global Commodity Chains, Central Asia

Hyperhidrosis: a new and often early symptom in Fabry disease. International experience and data from the Fabry Outcome Survey.

Hypohidrosis is a classic feature of Fabry disease; in contrast, hyperhidrosis has only been rarely described. The aim of the study is to characterise the baseline descriptive data on hyperhidrosis (frequency, age at onset, sex ratio and outcome with and without enzyme replacement therapy) in hemizygous male and heterozygous female patients with Fabry disease. We describe case histories of five patients with Fabry disease and hyperhidrosis seen at three different centres. We have also analysed a cohort of 21 paediatric patients in the UK and a large European cohort of patients enrolled in the Fabry Outcome Survey (FOS). Five patients (three female, two male) with hyperhidrosis were originally identified, although each had additional symptoms related to Fabry disease. The age at onset of hyperhidrosis was less than 18 years in four cases. In the cohort of 21 paediatric patients (12 female, nine male), one female had hyperhidrosis; the age at onset of this symptom was 11 years. In the FOS cohort, 66 of 714 patients with Fabry disease had hyperhidrosis (44 of 369 females, 11.9%; 22 of 345 males, 6.4%). The female predominance was observed in seven of nine countries from which data were analysed. Hyperhidrosis is an increasingly recognised feature of the Fabry disease phenotype. It is more prevalent in females than in males and often appears in childhood or adolescence. The efficacy of enzyme replacement therapy on this recently recognised symptom should be assessed.

China’s Strategy in North Africa: New economic challenges for the Mediterranean region

El WP té com a objectiu examinar per què els països del nord d'Àfrica estan augmentant les seves importacions de Xina i per què la Xina està augmentant les seves inversions estrangeres directes a la zona. la avantatges per als països del nord d'Àfrica es troben en els actuals acords de lliure comerç, el absència de barreres aranzelàries i la seva ubicació geogràfica summament beneficiosa com Hub de la Mediterrània. El paper de la Unió per la Mediterrània és clau per identificar aspectes de la política regional, tenint en compte la participació xinesa a la zona. com conseqüència, concloem que els actors polítics han de trobar un equilibri entre sostenible desenvolupament i els interessos econòmics de la regió.

The Distant neighbors — EU, Middle East, North Africa and the Euro-Mediterranean Partnership

The Barcelona Euro-Mediterranean Conference (1995) was intended to be a launching pad" for creating a new, innovative relationship between the EU-Fifteen and a selected set of non-member Middle Eastern and North African countries. The Barcelona Process was to become the European Union´s first attempt, of several, to create postmodern inclusive policy spheres as a way to deal with the post-enlargement problems of ´ins´ and outs´ in its immediate periphery. Nevertheless, in spite of geographical proximity, common problems and stated interest in creating amorphous EU borders in different sectors, the Euro-Mediterranean Partnership is today all but abandoned. This paper will examine some of the factors behind the current degeneration of the EU´s post-bipolar foreign policy strategy in the Mediterranean, by exploring the dialectic between the Union´s desire to expand its geopolitical, economic and cultural boundaries and the need to secure its territorial area (from migration, proliferation, social instability etc.). In the final part of the paper some suggestions for how to revive the relationship across the Mare Nostrum will be forwarded.

The Czech Republic in the European Union: A Problematic Member State?

A comparison between Poland, Hungary and the Czech Republic concerning regional cooperation, European Enlargement and further integration and relations with Germany might lead to the conclusion that the Czech Republic, once Member State of the European Union, might be more prone to cause tensions and problems than the other two countries

Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries.

With advances in the effectiveness of treatment and disease management, the contribution of chronic comorbid diseases (comorbidities) found within the Charlson comorbidity index to mortality is likely to have changed since development of the index in 1984. The authors reevaluated the Charlson index and reassigned weights to each condition by identifying and following patients to observe mortality within 1 year after hospital discharge. They applied the updated index and weights to hospital discharge data from 6 countries and tested for their ability to predict in-hospital mortality. Compared with the original Charlson weights, weights generated from the Calgary, Alberta, Canada, data (2004) were 0 for 5 comorbidities, decreased for 3 comorbidities, increased for 4 comorbidities, and did not change for 5 comorbidities. The C statistics for discriminating in-hospital mortality between the new score generated from the 12 comorbidities and the Charlson score were 0.825 (new) and 0.808 (old), respectively, in Australian data (2008), 0.828 and 0.825 in Canadian data (2008), 0.878 and 0.882 in French data (2004), 0.727 and 0.723 in Japanese data (2008), 0.831 and 0.836 in New Zealand data (2008), and 0.869 and 0.876 in Swiss data (2008). The updated index of 12 comorbidities showed good-to-excellent discrimination in predicting in-hospital mortality in data from 6 countries and may be more appropriate for use with more recent administrative data.

APRIL, a new ligand of the tumor necrosis factor family, stimulates tumor cell growth.

Members of the tumor necrosis factor (TNF) family induce pleiotropic biological responses, including cell growth, differentiation, and even death. Here we describe a novel member of the TNF family designated APRIL (for a proliferation-inducing ligand). Although transcripts of APRIL are of low abundance in normal tissues, high levels of mRNA are detected in transformed cell lines, and in human cancers of colon, thyroid, and lymphoid tissues in vivo. The addition of recombinant APRIL to various tumor cells stimulates their proliferation. Moreover, APRIL-transfected NIH-3T3 cells show an increased rate of tumor growth in nude mice compared with the parental cell line. These findings suggest that APRIL may be implicated in the regulation of tumor cell growth.

Peacetime Violence in El Salvador and Honduras: A tale of two countries

The end of the Cold War did not bring about an end to violence in Central America. Today, so-called non-political violence continues to worsen. Academics and public policymakers are frequently influenced by the assumption that there is a causal relationship between the political violence of the 1980s and the non-political violence of today. By looking at the cases of El Salvador and Honduras, this working paper seeks to systematize existing claims about the causal relationship between past and present violence into two approaches. Our research shows that high levels of prolonged political violence, along with an abundance of firearms, can lead to high levels of prolonged non-political violence but not in the ways most often cited in existing literature. We propose a new model to better understand the connection between past and present violence and recommend indicators that can be used to measure variations in violence over time in contexts of protracted non-political violence.

Neuroprotection in cerebral ischemia with XG-102, a new peptide inhibitor of JNK

Abstract Stroke or cerebrovascular accident, whose great majority is of ischemic nature, is the third leading cause of mortality and long lasting disability in industrialised countries. Resulting from the loss of blood supply to the brain depriving cerebral tissues of oxygen and glucose, it induces irreversible neuronal damages. Despite the large amount of research carried out into the causes and pathogenic features of cerebral ischemia the progress toward effective treatments has been poor. Apart the clot-busting drug tissue-type plasminogen activator (tPA) as effective therapy for acute stroke (reperfusion by thrombolysis) but limited to a low percentage of patients, there are currently no other approved medical treatments. The need for new therapy strategies is therefore imperative. Neuronal death in cerebral ischemia is among others due to excitotoxic mechanisms very early after stroke onset. One of the main involved molecular pathways leading to excitotoxic cell death is the c-Jun NH2-terminal kinase (JNK) pathway. Several studies have already shown the efficacy of a neuroprotective agent of a new type, a dextrogyre peptide synthesized in the retro inverso form (XG102, formerly D-JNKI1), which is protease-resistant and cell-penetrating and that selectively and strongly blocks the access of JNK to many of its targets. A powerful protection was observed with this compound in several models of ischemia (Borsello et al. 2003;Hirt et al. 2004). This chimeric compound, made up of a 10 amino acid TAT transporter sequence followed by a 20 amino acids JNK binding domain (JBD) sequence from JNK inhibitor protein (JIP) molecule, induced both a major reduction in lesion size and improved functional outcome. Moreover it presents a wide therapeutic window. XG-102 has proved its powerful efficacy in an occlusion model of middle cerebral artery in mice with intracérebroventricular (i.c.v.) injection but in order to be able to consider the development of this drug for human ischemic stroke it was therefore necessary to determine the feasibility of its systemic administration. The studies being the subject of this thesis made it possible to show a successful neuroprotection with XG-102 administered systemically after transient mouse middle cerebral artery occlusion (MCAo). Moreover our data. provided information about the feasibility to combine XG-102 with tPA without detrimental action on cell survival. By combining the benefits from a reperfusion treatment with the effects of a neuroprotective compound, it would represent the advantage of bringing better chances to protect the cerebral tissue. Résumé L'attaque cérébrale ou accident vasculaire cérébral, dont la grande majorité est de nature ischémique, constitue la troisième cause de mortalité et d'infirmité dans les pays industrialisés. Résultant de la perte d'approvisionnement de sang au cerveau privant les tissus cérébraux d'oxygène et de glucose, elle induit des dommages neuronaux irréversibles. En dépit du nombre élevé de recherches effectuées pour caractériser les mécanismes pathogènes de l'ischémie. cérébrale, les progrès vers des traitements efficaces restent pauvres. Excepté l'activateur tissulaire du plasminogène (tPA) dont le rôle est de désagréger les caillots sanguins et employé comme thérapie efficace contre l'attaque cérébrale aiguë (reperfusion par thrombolyse) mais limité à un faible pourcentage de patients, il n'y a actuellement aucun autre traitement médical approuvé. Le besoin de nouvelles stratégies thérapeutiques est par conséquent impératif. La mort neuronale dans l'ischémie cérébrale est entre autres due à des mécanismes excitotoxiques survenant rapidement après le début de l'attaque cérébrale. Une des principales voies moléculaires impliquée conduisant à la mort excitotoxique des cellules est la voie de la c-Jun NH2terminal kinase (JNK). Plusieurs études ont déjà montré l'efficacité d'un agent neuroprotecteur d'un nouveau type, un peptide dextrogyre synthétisé sous la forme retro inverso (XG-102, précédemment D-JNKI1) résistant aux protéases, capable de pénétrer dans les cellules et de bloquer sélectivement et fortement l'accès de JNK à plusieurs de ses cibles. Une puissante protection a été observée avec ce composé dans plusieurs modèles d'ischémie (Borsello et al. 2003;Hirt et al. 2004). Ce composé chimérique, construit à partir d'une séquence TAT de 10 acides aminés suivie par une séquence de 20 acides aminés d'un domaine liant JNK (JBD) issu de la molécule JNK protéine inhibitrice. (JIP), induit à la fois une réduction importante de la taille de lésion et un comportement fonctionnel amélioré. De plus il présente une fenêtre thérapeutique étendue. XG-102 a prouvé sa puissante efficacité dans un modèle d'occlusion de l'artère cérébrale moyenne chez la souris avec injection intracerebroventriculaire (i.c.v.) mais afin de pouvoir envisager le développement de ce composé pour l'attaque cérébrale chez l'homme, il était donc nécessaire de déterminer la faisabilité de son administration systémique. Les études faisant l'objet de cette thèse ont permis de montrer une neuroprotection importante avec XG-102 administré de façon systémique après l'occlusion transitoire de l'artère cérébrale moyenne chez la souris (MCAo). De plus nos données ont fourni des informations quant à la faisabilité de combiner XG-102 et tPA, démontrant une protection efficace par XG-102 malgré l'action nuisible du tPA sur la survie des cellules. En combinant les bénéfices de la reperfusion avec les effets d'un composé neurooprotecteur, cela représenterait l'avantage d'apporter des meilleures chances de protéger le tissu cérébral.

Legal europeanization as legal transformation : some insights from Swiss 'outer Europe'

The "Europeanization" of non-EU countries' laws is predominantly seen as an "export" of the EU acquis, especially in the case of so-called "quasi-member" states such as Switzerland. Based on an examination of the Swiss experience, this paper highlights the flaws of this conceptualization: the Europeanization of Swiss Law is a highly differentiated phenomenon, encompassing several forms of approximation to EU Law. All of these forms fall short of an "export" of norms, and result in the creation of something new: a "Europeanized law" that is similar to, but qualitatively different from, EU Law. Another drawback of the "export" metaphor is the emphasis it places on the isomorphism of positive legislation. Europeanization goes deeper than that. As shown in this paper, it is a process of transformation involving not only positive law, but also legal thinking. The Swiss case demonstrates how significant such deeper transformations can be: the Europeanization of positive law has induced an alteration of the traditional canon of legal interpretation. It also demonstrates how problematic such transformations can be: the above-mentioned alteration has not given rise to a new and universally accepted canon of interpretation. This reflects the tension between the need for clear "rules of reference" for EU legal materials - which are required in order to restore coherence and predictability to an extensively Europeanized legal system - and the reluctance to give a legal value to foreign legal materials - which is rooted in a traditional understanding of the concept of "law". Such tension, in turn, shows what deep and difficult transformations are required in order to establish a viable model of legal integration outside supranational structures.

TACI, an enigmatic BAFF/APRIL receptor, with new unappreciated biochemical and biological properties.

BAFF is a B cell survival factor that binds to three receptors BAFF-R, TACI and BCMA. BAFF-R is the receptor triggering naïve B cell survival and maturation while BCMA supports the survival of plasma cells in the bone marrow. Excessive BAFF production leads to autoimmunity, presumably as the consequence of inappropriate survival of self-reactive B cells. The function of TACI has been more elusive with TACI(-/-) mice revealing two sides of this receptor, a positive one driving T cell-independent immune responses and a negative one down-regulating B cell activation and expansion. Recent work has revealed that the regulation of TACI expression is intimately linked to the activation of innate receptors on B cells and that TACI signalling in response to multimeric BAFF and APRIL provides positive signals to plasmablasts. How TACI negatively regulates B cells remains elusive but may involve an indirect control of BAFF levels. The discovery of TACI mutations associated with common variable immunodeficiency (CVID) in humans not only reinforces its important role for humoral responses but also suggests a more complex role than first anticipated from knockout animals. TACI is emerging as an unusual TNF receptor-like molecule with a sophisticated mode of action.

Endocarditis prophylaxis revisited: experimental evidence of efficacy and new Swiss recommendations. Swiss Working Group for Endocarditis Prophylaxis.

Because of its severity, it is agreed that infectious endocarditis should be prevented whenever possible. Determining adequate prophylactic measures involves establishing (a) the patients at risk, (b) the procedures that might provoke bacteraemia, (c) the most effective prophylactic regimen, and (d) a balance between the risks of side effects from prophylaxis and of developing infectious endocarditis. Patients at risk and procedures inducing bacteraemia have been identified by clinical studies. On the other hand, the efficacy of prophylactic antibiotics has been based on animal studies. Randomised, placebo-controlled studies do not exist in humans because they would require large patient numbers and would raise ethical issues due to the severity of the disease. Case-control studies have indicated that infectious endocarditis prophylaxis is effective, but prevents only a limited number of cases. Animal experiments have revealed several key issues for human application. First, antibiotics do not prevent the early stages of valve colonisation, but rather kill the microorganisms after their attachment to the cardiac lesions. Second, the duration of antibiotic presence in the serum is critical. Under experimental conditions, the drugs must remain above their minimal inhibitory concentration for the organisms for > or = 10 h, to allow time for bacterial clearance from the valves. Third, antibiotic-induced killing is not the only mechanism allowing bacterial clearance. Other factors, such as platelet microbicidal proteins, may act in concert with the drugs to sterilise the lesions. Recommendations for prophylaxis have recently been revised in Europe and the USA. New information has improved the definition of groups at risk. Since most cases of infectious endocarditis are not preceded by medical procedures, primary prevention of infectious endocarditis should target infected foci responsible for spontaneous bacteraemia (e.g. poor dental hygiene). The purpose of this article is to update the existing recommendations in Switzerland, under the perspective of changing epidemiology, the availability of new drugs, and harmonisation with recommendations in other countries.

The Employment Precariousness Scale (EPRES): psychometric properties of a new tool for epidemiological studies among waged and salaried workers

Background: Despite the fact that labour market flexibility has resulted in an expansion of precarious employment in industrialized countries, to date there is limited empirical evidence about its health consequences. The Employment Precariousness Scale (EPRES) is a newly developed, theory-based, multidimensional questionnaire specifically devised for epidemiological studies among waged and salaried workers. Objective: To assess acceptability, reliability and construct validity of EPRES in a sample of waged and salaried workers in Spain. Methods: Cross-sectional study, using a sub-sample of 6.968 temporary and permanent workers from a population-based survey carried out in 2004-2005. The survey questionnaire was interviewer administered and included the six EPRES subscales, measures of the psychosocial work environment (COPSOQ ISTAS21), and perceived general and mental health (SF-36). Results: A high response rate to all EPRES items indicated good acceptability; Cronbach’s alpha coefficients, over 0.70 for all subscales and the global score, demonstrated good internal consistency reliability; exploratory factor analysis using principal axis analysis and varimax rotation confirmed the six-subscale structure and the theoretical allocation of all items. Patterns across known groups and correlation coefficients with psychosocial work environment measures and perceived health demonstrated the expected relations, providing evidence of construct validity. Conclusions: Our results provide evidence in support of the psychometric properties of EPRES, which appears to be a promising tool for the measurement of employment precariousness in public health research.

Introducing a new MRI classification of lumbar spinal stenosis based on cross-sectional morphology of the dural sac : 37

Introduction: Measures of the degree of lumbar spinal stenosis (LSS) such as antero-posterior diameter of the canal, and dural sac cross sectional area vary, and do not correlate with symptoms or results of surgery. We created a grading system, comprised of seven categories, based on the morphology of the dural sac and its contents as seen on T2 axial images. The categories take into account the ratio of rootlet/ CSF content. Grade A indicates no significant compression, grade D is equivalent to a total myelograhic block. We compared this classification with commonly used criteria of severity of stenosis. Methods: Fifty T2 axial MRI images taken at disc level from 27 symptomatic LSS patients undergoing decompressive surgery were classified twice by two radiologists and three spinal surgeons working at different institutions and countries. Dural sac cross-sectional surface area and AP diameter of the canal were measured both at disc and pedicle level from DICOM images using OsiriX software. Intraand inter-observer reliability were assessed using Cohen's, Fleiss' kappa statistics, and t test. Results: For the morphological grading the average intra-and inter observer kappas were 0.76 and 0.69+, respectively, for physicians working in the study originating country. Combining all observers the kappa values were 0.57 ± 0.19. and 0.44 ± 0.19, respectively. AP diameter and dural sac cross-sectional area measurements showed no statistically significant differences between observers. No correlation between morphological grading and AP diameter or dural sac crosssectional areawas observed in 13 (26%) and 8 cases (16%), respectively. Discussion: The proposed morphological grading relies on the identification of the dural sac and CSF better seen on full MRI series. This was not available to the external observers, which might explain the lower overall kappa values. Since no specific measurement tools are needed the grading suits everyday clinical practice and favours communication of degree of stenosis between practising physicians. The absence of a strict correlation with the dural sac surface suggests that measuring the surface alone might be insufficient in defining LSS as it is essentially a mismatch between the spinal canal and its contents. This grading is now adopted in our unit and further studies concentrating on relation between morphology, clinical symptoms and surgical results are underway.

Molecular taxonomy of the Formica rufa group (red wood ants) (Hymenoptera: Formicidae): a new cryptic species in the Swiss Alps?

Because of their beneficial impact on forest ecosystems, European red wood ants (Formica rufa group) are protected by law in many European countries and are considered to be among the most reliable bioindicators of forest stability. However, their taxonomy has been much debated and, unfortunately, it is too often neglected. This happens mainly because the morphology-based method for species delimitation requires lots of time and experience. We therefore employed 9 microsatellite loci and mitochondrial DNA (COI gene) to verify the power of genetic markers for red wood ant species delimitation and to investigate the cryptic diversity of these ants within the Eastern Swiss Alps. We analyzed 83 nests belonging to all red wood ant species that occur in the Swiss National Park area. Genetic data indicated that these species represent different genetic pools. Moreover, results showed that Formica aquilonia YARROW, 1955 and F. paralugubris SEIFERT, 1996 often hybridize within the Park, confirming that these two species are genetically very close and could have diverged only recently. Nevertheless, microsatellites also revealed that one entire population, located in the Minger Valley and morphologically identified as F. lugubris ZETTERSTEDT, 1838, is genetically different to all other analyzed F. lugubris populations found within the same area and to other red wood ant species. These findings, confirmed by mitochondrial DNA analyses, suggest the existence of a new cryptic species within the Eastern Swiss Alps. This putative cryptic species has been provisionally named F. lugubris-A2. These results have a great importance for future conservation plans, monitoring and evolutionary studies on these protected ants.