Annexations in Europe and the Persecution of Jews, 1939-1944

This contribution tries to explain why Jews were persecuted earlier or more fiercely in territories annexed by a state during World War II than in the mainland of that state. The case-studies covered are Nazi Germany, Romania, Hungary, Bulgaria, and the USSR. It is argued that internationally, similar policies of incorporation, especially the replacement of existing elites and the process of bringing in new settlers, worked against the Jews. Aside from focusing on governmental policies, the contribution also sketches the manner in which individual actions by state functionaries (who did not merely implement state policies) and by non-state actors had adverse effects on the Jewish population, impacting their survival chances. Finally, the article places the persecution of Jews in annexed areas in the context of the concerted violence conducted, at the same time, against other ethnically defined, religious, and social groups.

Fine-tuning of substrate architecture and surface chemistry promotes muscle tissue development

Tissue engineering has been increasingly brought to the scientific spotlight in response to the tremendous demand for regeneration, restoration or substitution of skeletal or cardiac muscle after traumatic injury, tumour ablation or myocardial infarction. In vitro generation of a highly organized and contractile muscle tissue, however, crucially depends on an appropriate design of the cell culture substrate. The present work evaluated the impact of substrate properties, in particular morphology, chemical surface composition and mechanical properties, on muscle cell fate. To this end, aligned and randomly oriented micron (3.3±0.8 μm) or nano (237±98 nm) scaled fibrous poly(ε-caprolactone) non-wovens were processed by electrospinning. A nanometer-thick oxygen functional hydrocarbon coating was deposited by a radio frequency plasma process. C2C12 muscle cells were grown on pure and as-functionalized substrates and analysed for viability, proliferation, spatial orientation, differentiation and contractility. Cell orientation has been shown to depend strongly on substrate architecture, being most pronounced on micron-scaled parallel-oriented fibres. Oxygen functional hydrocarbons, representing stable, non-immunogenic surface groups, were identified as strong triggers for myotube differentiation. Accordingly, the highest myotube density (28±15% of total substrate area), sarcomeric striation and contractility were found on plasma-coated substrates. The current study highlights the manifold material characteristics to be addressed during the substrate design process and provides insight into processes to improve bio-interfaces.

Sensitivity and specificity of fluorescence microlymphography for detecting lymphedema of the lower extremity

Fluorescence microlymphography (FML) is used to visualize the lymphatic capillaries. A maximum spread of the fluorescence dye of ≥ 12 mm has been suggested for the diagnosis of lymphedema. However, data on sensitivity and specificity are lacking. The aim of this study was to investigate the accuracy of FML for diagnosing lymphedema in patients with leg swelling. Patients with lower extremity swelling were clinically assessed and separated into lymphedema and non-lymphatic edema groups. FML was studied in all affected legs and the maximum spread of lymphatic capillaries was measured. Test accuracy and receiver operator characteristic (ROC) analysis was performed to assess possible threshold values that predict lymphedema. Between March 2008 and August 2011 a total of 171 patients (184 legs) with a median age of 43.5 (IQR 24, 54) years were assessed. Of those, 94 (51.1%) legs were diagnosed with lymphedema. The sensitivity, specificity, positive and negative likelihood ratio and positive and negative predictive value were 87%, 64%, 2.45, 0.20, 72% and 83% for the 12-mm cut-off level and 79%, 83%, 4.72, 0.26, 83% and 79% for the 14-mm cut-off level, respectively. The area under the ROC curve was 0.82 (95% CI: 0.76, 0.88). Sensitivity was higher in the secondary versus primary lymphedema (95.0% vs 74.3%, p = 0.045). No major adverse events were observed. In conclusion, FML is a simple and safe technique for detecting lymphedema in patients with leg swelling. A cut-off level of ≥ 14-mm maximum spread has a high sensitivity and high specificity of detecting lymphedema and should be chosen.

Clinical outcomes after zotarolimus and everolimus drug eluting stent implantation in coronary artery bifurcation lesions: insights from the RESOLUTE All Comers Trial

OBJECTIVE We investigated clinical outcomes after treatment of coronary bifurcation lesions with second generation drug eluting stents (DES). DESIGN Post hoc analysis of a randomised, multicentre, non-inferiority trial. SETTING Multicentre study. PATIENTS All comers study with minimal exclusion criteria. INTERVENTIONS Patients were treated with either zotarolimus or everolimus eluting stents. The patient population was divided according to treatment of bifurcation or non-bifurcation lesions and clinical outcomes were compared between groups. MAIN OUTCOMES MEASURES Clinical outcomes within 2-year follow-up. RESULTS A total of 2265 patients were included in the present analysis. Two-year follow-up data were available in 2223 patients: 1838 patients in the non-bifurcation group and 385 patients in the bifurcation group. At 2-year follow-up the bifurcation and the non-bifurcation lesion groups showed no significant differences in terms of cardiac death (2.3 vs 2.1, p=0.273), target lesion failure (9.7% vs 13.8%, p=0.255), major adverse cardiac events (11.5% vs 15.1%, p=0.305), target lesion revascularisation (4.7% vs 6.0%, p=0.569), and definite or probable stent thrombosis (1.6% vs 1.8%, p=0.419). CONCLUSIONS The use of second generation DES for the treatment of coronary bifurcation lesions was associated with similar long term mortality and clinical outcomes compared with non-bifurcation lesions.

Effect of pressure-controlled intermittent coronary sinus occlusion (PICSO) on myocardial ischaemia and reperfusion in a closed-chest porcine model

AIMS To investigate a pressure-controlled intermittent coronary sinus occlusion (PICSO) system in an ischaemia/reperfusion model. METHODS AND RESULTS We randomly assigned 18 pigs subjected to 60 minutes ischaemia by left anterior descending (LAD) coronary artery balloon occlusion to PICSO (n=12, groups A and B) or to controls (n=6, group C). PICSO started 10 minutes before (group A), or 10 minutes after (group B) reperfusion and was maintained for 180 minutes. A continuous drop of distal LAD pressure was observed in group C. At 180 minutes of reperfusion, LAD diastolic pressure was significantly lower in group C compared to groups A and B (p=0.02). LAD mean pressure was significantly less than the systemic arterial mean pressure in group C (p=0.02), and the diastolic flow slope was flat, compared to groups A and B (p=0.03). IgG and IgM antibody deposition was significantly higher in ischaemic compared to non-ischaemic tissue in group C (p<0.05). Significantly more haemorrhagic lesions were seen in the ischaemic myocardium of group C, compared to groups A and B (p=0.002). The necrotic area differed non-significantly among groups. CONCLUSIONS PICSO was safe and effective in improving coronary perfusion pressure and reducing antibody deposition consistent with reduced microvascular obstruction and ischaemia/reperfusion injury.

Avant-garde or supplement? Advisory bodies of transnational associations as alternatives to the League’s Minority Protection System, 1919-1939

This exegesis focuses on the work of minority committees of transnational associations in the interwar period. Most of their members considered the League system to be inefficient and supported the establishment of non-state alternatives, which included private investigations on the spot, publicity for specific problems of minorities, and attempts to reconcile representatives of ethnic minorities with those of the majority. Members of non-involved states were pre-destined especially to act as neutral moderators. Only those in close contact with League officials avoided being misused by political forces that did not seek reconciliation but border revision. They learnt that the League rules looked inadequate from the outside but turned out to be useful in coming to applicable solutions once they started their own alternative methods. Their publications and investigative journeys turned out to deepen the problems, whilst their reconciliation work became an appreciated supplement of the League system.

Book Review: Regulating Code : Good Governance and Better Regulation in the Information Age

Digital technologies have profoundly changed not only the ways we create, distribute, access, use and re-use information but also many of the governance structures we had in place. Overall, "older" institutions at all governance levels have grappled and often failed to master the multi-faceted and multi-directional issues of the Internet. Regulatory entrepreneurs have yet to discover and fully mobilize the potential of digital technologies as an influential factor impacting upon the regulability of the environment and as a potential regulatory tool in themselves. At the same time, we have seen a deterioration of some public spaces and lower prioritization of public objectives, when strong private commercial interests are at play, such as most tellingly in the field of copyright. Less tangibly, private ordering has taken hold and captured through contracts spaces, previously regulated by public law. Code embedded in technology often replaces law. Non-state action has in general proliferated and put serious pressure upon conventional state-centered, command-and-control models. Under the conditions of this "messy" governance, the provision of key public goods, such as freedom of information, has been made difficult or is indeed jeopardized.The grand question is how can we navigate this complex multi-actor, multi-issue space and secure the attainment of fundamental public interest objectives. This is also the question that Ian Brown and Chris Marsden seek to answer with their book, Regulating Code, as recently published under the "Information Revolution and Global Politics" series of MIT Press. This book review critically assesses the bold effort by Brown and Marsden.

The kynurenine pathway is involved in bacterial meningitis.

BackgroundBacterial meningitis (BM) is characterized by an intense host inflammatory reaction, which contributes to the development of brain damage and neuronal sequelae. Activation of the kynurenine (KYN) pathway (KP) has been reported in various neurological diseases as a consequence of inflammation. Previously, the KP was shown to be activated in animal models of BM, and the association of the SNP AADAT¿+¿401C/T (kynurenine aminotransferase II - KAT II) with the host immune response to BM has been described. The aim of this study was to investigate the involvement of the KP during BM in humans by assessing the concentrations of KYN metabolites in the cerebrospinal fluid (CSF) of BM patients and their relationship with the inflammatory response compared to aseptic meningitis (AM) and non-meningitis (NM) groups.MethodsThe concentrations of tryptophan (TRP), KYN, kynurenic acid (KYNA) and anthranilic acid (AA) were assessed by HPLC from CSF samples of patients hospitalized in the Giselda Trigueiro Hospital in Natal (Rio Grande do Norte, Brazil). The KYN/TRP ratio was used as an index of indoleamine 2,3-dioxygenase (IDO) activity, and cytokines were measured using a multiplex cytokine assay. The KYNA level was also analyzed in relation to AADAT¿+¿401C/T genotypes.ResultsIn CSF from patients with BM, elevated levels of KYN, KYNA, AA, IDO activity and cytokines were observed. The cytokines INF-¿ and IL-1Ra showed a positive correlation with IDO activity, and TNF-¿ and IL-10 were positively correlated with KYN and KYNA, respectively. Furthermore, the highest levels of KYNA were associated with the AADAT¿+¿401 C/T variant allele.ConclusionThis study suggests a downward modulatory effect of the KP on CSF inflammation during BM.

Sustainability principles put into practice: case studies of network analysis in Swiss climate change adaptation

Climate adaptation policies increasingly incorporate sustainability principles into their design and implementation. Since successful adaptation by means of adaptive capacity is recognized as being dependent upon progress toward sustainable development, policy design is increasingly characterized by the inclusion of state and non-state actors (horizontal actor integration), cross-sectoral collaboration, and inter-generational planning perspectives. Comparing four case studies in Swiss mountain regions, three located in the Upper Rhone region and one case from western Switzerland, we investigate how sustainability is put into practice. We argue that collaboration networks and sustainability perceptions matter when assessing the implementation of sustainability in local climate change adaptation. In other words, we suggest that adaptation is successful where sustainability perceptions translate into cross-sectoral integration and collaboration on the ground. Data about perceptions and network relations are assessed through surveys and treated via cluster and social network analysis.

Biochemical changes in barley plants after excessive supply of copper and manganese

The present study was undertaken to identify changes in some important proteins involved in CO2 fixation (Rubisco, Rubisco activase (RA), Rubisco binding protein (RBP)), NH4+ assimilation (glutamine synthetase (GS) and glutamate synthase (GOGAT)), using immunoblotting, and in the antioxidative defense as a result of Cu or Mn excess in barley leaves (Hordeum vulgare L. cv. Obzor). Activities and isoenzyme patterns of superoxide dismutase (SOD), ascorbate peroxidase (APX), guaiacol peroxidase (GPX) and catalase (CAT), as well as the levels of ascorbate (ASC), non-protein sulfhydryl groups, hydrogen peroxide and oxidative damage to proteins were determined. Data were correlated to the accumulation of Cu or Mn in the leaves after 5 days supply of heavy metal (HM) excess in the nutrient solution. In the highest Cu excess (1500 μM), Rubisco LS and SS were reduced considerably whereas under the highest Mn concentrations (18,300 μM) only minor changes in Rubisco subunits were detected. The RBP was diminished under the highest concentrations of both Cu or Mn. The bands of RA changed differently comparing Cu and Mn toxicity. GS decreased and GOGAT was absent under the highest concentration of Cu. At Mn excess Fd-GOGAT diminished whereas GS was not apparently changed. The development of toxicity symptoms corresponded to an accumulation of Cu or Mn in the leaves and to a gradual increase in protein carbonylation, a lower SOD activity and elevated CAT and GPX activities. APX activity was diminished under Mn toxicity and was not changed under Cu excess. Generally, changes in the isoenzyme profiles were similar under both toxicities. An accumulation of H2O2 was observed only at Mn excess. Contrasting changes in the low-molecular antioxidants were detected when comparing both toxicities. Cu excess affected mainly the non-protein SH groups, while Mn influenced the ASC content. Oxidative stress under Cu or Mn toxicity was most probably the consequence of depletion in low-molecular antioxidants as a result of their involvement in detoxification processes and disbalance in antioxidative enzymes. The link between heavy metal accumulation in leaves, leading to different display of oxidative stress, and changes in individual chloroplast proteins is discussed in the article.

Europeanization and the inclusive strategies of executive actors

In Europeanized policy domains, executive actors are considered especially powerful because they are directly responsible for international negotiations. However, in order to avoid failing in the ratification process, they are also highly dependent on the support of domestic, non-state actors. We argue that in Europeanized decision-making processes, state actors are not passively lobbied, but actively seek collaboration with - and support from - domestic actors. We apply stochastic actor-based modelling for network dynamics to collaboration data on two successive bilateral agreements on the free movement of persons between Switzerland and the European Union (EU). Results confirm our hypotheses that state actors are not passively lobbied, but actively look for collaboration with other actors, and especially with potential veto players and euro-sceptical actors from both the conservative Right and the Left.

Climate change in mountain regions: how local communities adapt to extreme events

This paper examines how local communities adapt to climate change and how governance structures can foster or undermine adaptive capacity. Climate change policies, in general, and disaster risk management in mountain regions, in particular, are characterised by their multi-level and multi-sectoral nature during formulation and implementation. The involvement of numerous state and non-state actors at local to national levels produces a variety of networks of interaction and communication. The paper argues that the structure of these relational patterns is critical for understanding adaptive capacity. It thus proposes an expanded concept of adaptive capacity that incorporates (horizontal and vertical) actor integration and communication flow between these actors. The paper further advocates the use of formal social network analysis to assess these relational patterns. Preliminary results from research on adaptation to climate change in a Swiss mountain region vulnerable to floods and other natural hazards illustrate the conceptual and empirical significance of the main arguments.

On the modeling of drug induced respiratory depression in the non-steady-state

The ability of anesthetic agents to provide adequate analgesia and sedation is limited by the ventilatory depression associated with overdosing in spontaneously breathing patients. Therefore, quantitation of drug induced ventilatory depression is a pharmacokinetic-pharmacodynamic problem relevant to the practice of anesthesia. Although several studies describe the effect of respiratory depressant drugs on isolated endpoints, an integrated description of drug induced respiratory depression with parameters identifiable from clinically available data is not available. This study proposes a physiological model of CO2 disposition, ventilatory regulation, and the effects of anesthetic agents on the control of breathing. The predictive performance of the model is evaluated through simulations aimed at reproducing experimental observations of drug induced hypercarbia and hypoventilation associated with intravenous administration of a fast-onset, highly potent anesthetic mu agonist (including previously unpublished experimental data determined after administration of 1 mg alfentanil bolus). The proposed model structure has substantial descriptive capability and can provide clinically relevant predictions of respiratory inhibition in the non-steady-state to enhance safety of drug delivery in the anesthetic practice.