Das Ende der bilateralen Handelsabkommen?: Was Mega-Abkommen wie das Freihandelsabkommen EU-USA (TTIP) für die Schweiz bedeuten

Zwei Jahrzehnte lang hat sich im internationalen Handelsrecht wenig bewegt. Durch die Paralyse der WTO genossen bilaterale Handelsabkommen viel Aufmerksamkeit und waren während 20 Jahren das primäre Instrument für die Weiterentwicklung und Vertiefung der Handelsbeziehungen. Vor gut einem Jahr hat sich die Dynamik geändert: Mit mehreren sogenannten Mega-Abkommen, plurilateralen Initiativen und dem ersten neuen Entscheid der WTO seit vielen Jahren, verlieren bilaterale Handelsabkommen an Attraktivität und Nutzen. Diese neue Dynamik bringt deutlich zum Vorschein, dass der handelspolitische Alleingang steigende Kosten mit sich bringt und die fortschreitende Globalisierung einen Imperativ zur Vernetzung und Kooperation schafft. Ob die Schweiz bereit ist, der neuen Herausforderung proaktiv zu begegnen, wird sich weisen.

Labour Migration, Trade and Investment: From Fragmentation to Coherence

Trade, investment and migration are strongly intertwined, being three key factors in international production. Yet, law and regulation of the three has remained highly fragmented. Trade is regulated by the WTO on the multilateral level, and through preferential trade agreements on the regional and bilateral levels – it is fragmented and complex in its own right. Investment, on the other hand, is mainly regulated through bilateral investment treaties with no strong links to the regulation of trade or migration. And, finally, migration is regulated by a web of different international, regional and bilateral agreements which focus on a variety of different aspects of migration ranging from humanitarian to economic. The problems of institutional fragmentation in international law are well known. There is no organizational forum for coherent strategy-making on the multilateral level covering all three areas. Normative regulations may thus contradict each other. Trade regulation may bring about liberalization of access for service providers, but eventually faces problems in recruiting the best people from abroad. Investors may withdraw investment without being held liable for disruptions to labour and to the livelihood and infrastructure of towns and communities affected by disinvestment. Finally, migration policies do not seem to have a significant impact as long as trade policies and investment policies are not working in a way that is conducive to reducing migration pressure, as trade and investment are simply more powerful on the regulatory level than migration. This chapter addresses the question as to how fragmentation of the three fields could be reme-died and greater coherence between these three areas of factor allocation in international economic relations and law could be achieved. It shows that migration regulation on the international level is lagging behind that on trade and investment. Stronger coordination and consideration of migration in trade and investment policy, and stronger international cooperation in migration, will provide the foundations for a coherent international architecture in the field.

The Dialectical Relationship of Preferential and Multilateral Trade Agreements

Preferentialism and multilateralism are not two independent and succinct avenues in the pur-suit of market access and regulatory policies. They historically build upon each other in a dialectical process, closely related and linked through regulatory bridges and references. They influence and direct each other in various ways. The paper mainly focuses on the evolution of international protection of intellectual property rights and of services. The multilateral regulation of the TRIPS and others derive from years of regulatory experience and high numbers of preferential agreements across the globe. The GATS and others, on the other hand, have entered the pluri- or multilateral stage early. Once regulation has reached the mul-tilateral stage, preferentialism focuses on WTO-plus and -extra commitments. Both areas, however, show close interaction. The principle of MFN ensures that multilateralism and preferentialism do not evolve independently from each other. It produces significant spill-over effects of preferential agreements. Such effects and the need to develop uniform and coherent regulatory standards have led in parallel to a number of preferential, plurilateral and multilateral regulatory initiatives. We submit that the process will eventually encourage the return to multilateralism and negotiations in international fora, in particular the WTO while traditional market access may stay with preferential relations among Nations. Such burden-sharing between different regulatory fora should be reflected in future WTO rules providing the overall backbone of the system.

Legal Aspects of Sino-­African Tied Aid: The Art of Playing with a Legal Grey Area

Sino-African trade has seen a fifty-fold increase in the years 1999 to 2008. In some African regions, particularly in sub-Saharan Africa, China has even replaced the US as the most important trading partner today. But China holds not a single FTA on the African continent, while other major trading partners of African economies rely on an extensive framework of different trade agreements. What is, thus, the legal basis of the recent increase of Sino-African trade? Interestingly, Sino-African trade has seen a particularly strong increase in countries that have entered into tied aid agreements with China. These agreements are commonly known under the term ‘Angola-Model’ and consist of a multifaceted network of barter-trading-systems, aspects of tied aid and concessions for oil and other commodities linked with a state loan. It is likely that these agreements have an impact on the trade-flows between African countries and China. This paper discusses the legal character of this new form of economic cooperation, or modern version of tied aid. Critical legal aspects related to this form of tied aid refer to violation of the principle of most-favoured nation (MFN), illegitimate export subsidies, market access, public procurement and transparency in the international trading system. However, despite the recent outcry of the foremost Western community against the strategy of the Chinese government on the African continent, the practice of the Angola-Model based tied aid is not entirely new, and neither is it against the law. The case of tied aid is situated in a legal grey area that should be examined thoroughly in order to strengthen the international trading system and to support developing countries in their attempt to gain from tied aid arrangements.

Der Dritte Weg zur Vierten Freiheit: Von bestehenden und künftigen Konflikten zwischen Handels- und Migrationsrecht

In Freihandelsabkommen wird der sogenannte Mode 4 der Dienstleistungserbringung – die Präsenz natürlicher Personen zur Dienstleistungserbringung im anderen Vertragsstaat – immer wichtiger. Einige dieser Abkommen, welche die Schweiz allein oder im Rahmen der EFTA mit Drittstaaten abgeschlossen hat, verschaffen Dienstleistungserbringern Rechte, die deutlich über die Rechte aus dem GATS und über das Schweizer Ausländergesetz hinausgehen. In ihnen liegt daher eine bisher wenig beachtete Quelle für Ansprüche auf Einreise und Aufenthalt. Richtigerweise müsste das Einreiseverfahren dem Rechtsanspruch von Mode 4 Dienstleistungserbringern gerecht werden, indem erleichterte Bedingungen zugestanden werden. Für manche Abkommen bedeutet das in erster Linie eine Ausnahme von der Kontingentierung. Diese Privilegierung einzulösen ist nach der Annahme der Masseneinwanderungsinitiative noch schwieriger geworden und könnte sich in Zukunft als Hindernis erweisen in der Verfolgung von Freihandelsinteressen der Schweiz.

Variationen der regionalen Personenfreizügigkeit: Die schrittweise Öffnung des Arbeitsmarktes

Während die Schweiz, Europa und die USA an ihren präferierten Bestimmungen zur Personenfreizügigkeit festhalten, entstehen im globalen Süden neue Formen der regulierten Arbeitsmarktöffnung. Dieser Beitrag illustriert das weite Spektrum der juristischen Möglichkeiten für eine regulierte, schrittweise Öffnung des Arbeitsmarkts, so wie sie heute zwischen Entwicklungsländern am Entstehen ist. Da zudem ein Zusammenhang zwischen Personenfreizügigkeit und nachhaltigem Wirtschaftswachstum besteht, insbesondere in Verbindung mit regionaler wirtschaftlicher Integration zwischen Entwicklungsländern, erhält der Diskurs über Variationen der regionalen Personenfreizügigkeit auch eine migrations- und aussenpolitische Dimension. Dies bedeutet, dass der Schweiz im Rahmen von Freihandelsabkommen eine Reihe von Möglichkeiten offen stehen, den Arbeitsmarkt schrittweise für internationale Talente zu öffnen, und sich ein Engagement für die wirtschaftliche Integration in südlichen Regionen auch für den Wirtschaftsstandort Schweiz lohnt.

Deficiency of ECHS1 causes mitochondrial encephalopathy with cardiac involvement.

OBJECTIVE Short-chain enoyl-CoA hydratase (ECHS1) is a multifunctional mitochondrial matrix enzyme that is involved in the oxidation of fatty acids and essential amino acids such as valine. Here, we describe the broad phenotypic spectrum and pathobiochemistry of individuals with autosomal-recessive ECHS1 deficiency. METHODS Using exome sequencing, we identified ten unrelated individuals carrying compound heterozygous or homozygous mutations in ECHS1. Functional investigations in patient-derived fibroblast cell lines included immunoblotting, enzyme activity measurement, and a palmitate loading assay. RESULTS Patients showed a heterogeneous phenotype with disease onset in the first year of life and course ranging from neonatal death to survival into adulthood. The most prominent clinical features were encephalopathy (10/10), deafness (9/9), epilepsy (6/9), optic atrophy (6/10), and cardiomyopathy (4/10). Serum lactate was elevated and brain magnetic resonance imaging showed white matter changes or a Leigh-like pattern resembling disorders of mitochondrial energy metabolism. Analysis of patients' fibroblast cell lines (6/10) provided further evidence for the pathogenicity of the respective mutations by showing reduced ECHS1 protein levels and reduced 2-enoyl-CoA hydratase activity. While serum acylcarnitine profiles were largely normal, in vitro palmitate loading of patient fibroblasts revealed increased butyrylcarnitine, unmasking the functional defect in mitochondrial β-oxidation of short-chain fatty acids. Urinary excretion of 2-methyl-2,3-dihydroxybutyrate - a potential derivative of acryloyl-CoA in the valine catabolic pathway - was significantly increased, indicating impaired valine oxidation. INTERPRETATION In conclusion, we define the phenotypic spectrum of a new syndrome caused by ECHS1 deficiency. We speculate that both the β-oxidation defect and the block in l-valine metabolism, with accumulation of toxic methacrylyl-CoA and acryloyl-CoA, contribute to the disorder that may be amenable to metabolic treatment approaches.

How many species of cichlid fishes are there in African lakes?

The endemic cichlid fishes of Lakes Malawi, Tanganyika and Victoria are textbook examples of explosive speciation and adaptive radiation, and their study promises to yield important insights into these processes. Accurate estimates of species richness of lineages in these lakes, and elsewhere, will be a necessary prerequisite for a thorough comparative analysis of the intrinsic and extrinsic factors influencing rates of diversification. This review presents recent findings on the discoveries of new species and species flocks and critically appraises the relevant evidence on species richness from recent studies of polymorphism and assortative mating, generally using behavioural and molecular methods. Within the haplochromines, the most species-rich lineage, there are few reported cases of postzygotic isolation, and these are generally among allopatric taxa that are likely to have diverged a relatively long time in the past. However, many taxa, including many which occur sympatrically and do not interbreed in nature, produce viable, fertile hybrids. Prezygotic barriers are more important, and persist in laboratory conditions in which environmental factors have been controlled, indicating the primary importance of direct mate preferences. Studies to date indicate that estimates of alpha (within-site) diversity appear to be robust. Although within-species colour polymorphisms are common, these have been taken into account in previous estimates of species richness. However, overall estimates of species richness in Lakes Malawi and Victoria are heavily dependent on the assignation of species status to allopatric populations differing in male colour. Appropriate methods for testing the specific status of allopatric cichlid taxa are reviewed and preliminary results presented.

Schnidejoch und Lötschenpass. Archäologische Forschungen in den Berner Alpen. Schnidejoch et Lötschenpass. Investigations archéologiques dans les Alpes bernoises.

Archäologie in den Hochalpen: Vom Rückgang der Gletscher sind auch archäologische Objekte betroffen. Über Jahrtausende hinweg haben sie im Eis überdauert, nun kommen sie zum Vorschein. Im Hitzesommer 2003 fand eine Wanderin am Schnidejoch ein fremdartiges Objekt aus Birkenrinde. Es erwies sich als Teil eines 4800 Jahre alten Bogenfutterals. In den Jahren 2004 bis 2011 unternahm der Archäologische Dienst des Kantons Bern über 30 Begehungen der Nordseite und – zusammen mit der Walliser Kantonsarchäologie – auch der Südseite des Schnidejochs. Zahlreiche weitere Funde aus Holz, Leder und Metall konnten geborgen und wissenschaftlich untersucht werden. Einzigartige Funde Zu den spektakulärsten Funden vom Schnidejoch zählt das Bogenfutteral aus Birkenrinde. Weiter stechen aus den rund 900 Funden ein Pfeilbogen, mehrere vollständige Pfeile und Fragmente einer Schale aus Ulmenholz hervor. Es handelt sich dabei um das älteste Holzgefäss der Schweiz. Weitere herausragende Funde sind ein bronzezeitliches Holzgefäss aus Birkenrinde, eine bronzezeitliche Gewandnadel sowie Bekleidung und Schuhe aus Leder. Archéologie dans les Alpes bernoises Le recul des glaciers a aussi un impact sur les découvertes archéologiques. Il fait réapparaître des objets préservés dans les glaces depuis des millénaires. Pendant l’été caniculaire de 2003, une randonneuse a découvert un objet singulier en écorce de bouleau, qui s’est avéré être un morceau de carquois vieux de 4800 ans. De 2004 à 2011, le Service archéologique du canton de Berne s’est rendu plus de trente fois sur le versant nord du Schnidejoch et, en collaboration avec le Service d’archéologie du canton du Valais, sur le versant sud de ce col. De nombreux autres objets en bois, cuir et métal ont pu être mis au jour et étudiés scientifiquement. Des découvertes uniques Le carquois en écorce de bouleau constitue l’une des découvertes les plus sensationnelles du Schnidejoch. Parmi les quelque 900 objets mis au jour figurent un arc, plusieurs flèches complètes et les fragments d’un bol en bois d’orme. Ce bol est le plus ancien récipient en bois de Suisse. D’autres trouvailles spectaculaires ont été faites, notamment un récipient en écorce de bouleau et une épingle à vêtements datant de l’Âge du Bronze ainsi que des vêtements et des chaussures en cuir.

Determination of vertebral range of motion using inertial measurement units in 27 Franches-Montagnes stallions and comparison between conditions and with a mixed population

REASONS FOR PERFORMING STUDY: The diagnosis of equine back disorders is challenging. Objectively determining movement of the vertebral column may therefore be of value in a clinical setting. OBJECTIVES: To establish whether surface-mounted inertial measurement units (IMUs) can be used to establish normal values for range of motion (ROM) of the vertebral column in a uniform population of horses trotting under different conditions. STUDY DESIGN: Vertebral ROM was established in Franches-Montagnes stallions and a general population of horses and the variability in measurements compared between the two groups. Repeatability and the influence of specific exercise condition (on ROM) were assessed. Finally, attempts were made to explain the findings of the study through the evaluation of factors that might influence ROM. METHODS: Dorsoventral (DV) and mediolateral (ML) vertebral ROM was measured at a trot under different exercise conditions in 27 Franches-Montagnes stallions and six general population horses using IMUs distributed over the vertebral column. RESULTS: Variability in the ROM measurements was significantly higher for general population horses than for Franches-Montagnes stallions (both DV and ML ROM). Repeatability was strong to very strong for DV measurements and moderate for ML measurements. Trotting under saddle significantly reduced the ROM, with sitting trot resulting in a significantly lower ROM than rising trot. Age is unlikely to explain the low variability in vertebral ROM recorded in the Franches-Montagnes horses, while this may be associated with conformational factors. CONCLUSIONS: It was possible to establish a normal vertebral ROM for a group of Franches-Montagnes stallions. While within-breed variation was low in this population, further studies are necessary to determine variation in vertebral ROM for other breeds and to assess their utility for diagnosis of equine back disorders.

Dystrophic cardiomyopathy: role of TRPV2 channels in stretch-induced cell damage

Aims Duchenne muscular dystrophy (DMD), a degenerative pathology of skeletal muscle, also induces cardiac failure and arrhythmias due to a mutation leading to the lack of the protein dystrophin. In cardiac cells, the subsarcolemmal localization of dystrophin is thought to protect the membrane from mechanical stress. The absence of dystrophin results in an elevated stress-induced Ca2+ influx due to the inadequate functioning of several proteins, such as stretch-activated channels (SACs). Our aim was to investigate whether transient receptor potential vanilloid channels type 2 (TRPV2) form subunits of the dysregulated SACs in cardiac dystrophy. Methods and results We defined the role of TRPV2 channels in the abnormal Ca2+ influx of cardiomyocytes isolated from dystrophic mdx mice, an established animal model for DMD. In dystrophic cells, western blotting showed that TRPV2 was two-fold overexpressed. While normally localized intracellularly, in myocytes from mdx mice TRPV2 channels were translocated to the sarcolemma and were prominent along the T-tubules, as indicated by immunocytochemistry. Membrane localization was confirmed by biotinylation assays. Furthermore, in mdx myocytes pharmacological modulators suggested an abnormal activity of TRPV2, which has a unique pharmacological profile among TRP channels. Confocal imaging showed that these compounds protected the cells from stress-induced abnormal Ca2+ signals. The involvement of TRPV2 in these signals was confirmed by specific pore-blocking antibodies and by small-interfering RNA ablation of TRPV2. Conclusion Together, these results establish the involvement of TRPV2 in a stretch-activated calcium influx pathway in dystrophic cardiomyopathy, contributing to the defective cellular Ca2+ handling in this disease.

Adult Pleomorphic Rhabdomyosarcoma: A Multicentre Retrospective Study.

BACKGROUND Pleomorphic rhabdomyosarcoma (RMS) is a rare sub-type of RMS. Optimal treatment remains undefined. PATIENTS AND METHODS Between 1995 and 2014, 45 patients were diagnosed and treated in three tertiary sarcoma Centers (United Kingdom, Switzerland and Germany). Treatment characteristics and outcomes were analyzed. RESULTS The median age at diagnosis was 71.5 years (range=28.4-92.8 years). Median survival for those with localised (n=32, 71.1%) and metastatic disease (n=13, 28.9%) were 12.8 months (95% confidence interval=8.2-34.4) and 7.1 months (95% confidence interval=3.8-11.3) respectively. The relapse rate was 53.8% (four local and 10 distant relapses). In total, 14 (31.1%) patients received first line palliative chemotherapy including multi-agent paediatric chemotherapy schedules (n=3), ifosfamide-doxorubicin (n=4) and single-agent doxorubicin (n=7). Response to chemotherapy was poor (one partial remission with vincristine-actinomycin D-cyclophosphamide and six cases with stable disease). Median progression-free survival was 2.3 (range=1.2-7.3) months. CONCLUSION Pleomorphic RMS is an aggressive neoplasm mainly affecting older patients, associated with a high relapse rate, a poor and short-lived response to standard chemotherapy and an overall poor prognosis for both localised and metastatic disease.

Constraining age distributions of groundwater from public supply wells in diverse hydrogeological settings in Scania, Sweden

Twenty-five public supply wells throughout the hydrogeologically diverse region of Scania, southern Sweden are subjected to environmental tracer analysis (³H–³He,⁴He, CFCs, SF₆ and for one well only also ⁸⁵Kr and ³⁹Ar) to study well and aquifer vulnerability and evaluate possibilities of groundwater age distribution assessment. We find CFC and SF₆ concentrations well above solubility equilibrium with modern atmosphere, indicating local contamination, as well as indications of CFC degradation. The tracer-specific complications considerably constrain possibilities for sound quantitative regional ground- water age distribution assessment and demonstrate the importance of initial qualitative assessment of tracer-specific reliability, as well a need for additional, complementary tracers (e.g. ⁸⁵Kr,³⁹Ar and potentially also ¹⁴C). Lumped parameter modelling yields credible age distribution assessments for representative wells in four type aquifers. Pollution vulnerability of the aquifer types was based on the selected LPM models and qualitative age characterisation. Most vulnerable are unconfined dual porosity and fractured bedrock aquifers, due to a large component of very young groundwater. Unconfined sedimentary aquifers are vulnerable due to young groundwater and a small pre-modern component. Less vulnerable are semi-confined sedimentary or dual-porosity aquifers, due to older age of the modern component and a larger pre-modern component. Confined aquifers appear least vulnerable, due an entirely pre-modern groundwater age distribution (recharged before 1963). Tracer complications aside, environmental tracer analyses and lumped parameter modelling aid in vulnerability assessment and protection of regional groundwater resources.

Subunit composition of VRAC channels determines substrate specificity and cellular resistance to Pt-based anti-cancer drugs

Although platinum-based drugs are widely used chemotherapeutics for cancer treatment, the determinants of tumor cell responsiveness remain poorly understood. We show that the loss of subunits LRRC8A and LRRC8D of the heteromeric LRRC8 volume-regulated anion channels (VRACs) increased resistance to clinically relevant cisplatin/carboplatin concentrations. Under isotonic conditions, about 50% of cisplatin uptake depended on LRRC8A and LRRC8D, but neither on LRRC8C nor on LRRC8E. Cell swelling strongly enhanced LRRC8-dependent cisplatin uptake, bolstering the notion that cisplatin enters cells through VRAC. LRRC8A disruption also suppressed drug-induced apoptosis independently from drug uptake, possibly by impairing VRAC-dependent apoptotic cell volume decrease. Hence, by mediating cisplatin uptake and facilitating apoptosis, VRAC plays a dual role in the cellular drug response. Incorporation of the LRRC8D subunit into VRAC substantially increased its permeability for cisplatin and the cellular osmolyte taurine, indicating that LRRC8 proteins form the channel pore. Our work suggests that LRRC8D-containing VRACs are crucial for cell volume regulation by an important organic osmolyte and may influence cisplatin/carboplatin responsiveness of tumors.