Through the glass ceiling: the EU as a developing security regime for Europe?

This article examines the way in which the EU has moved beyond its traditional, cold war role, and has extended its role in the sphere of security policies. Enlargement to the east and south is one of the most effective ways in which the EU can extend its influence, and through which it can help to create a zone of security, peace and prosperity in Europe. However, the focus of this article is not upon enlargement itself, but the growth of the EU’s role as a provider of security beyond its existing frontiers. The characteristics of international institutions are best understood through three levels of analysis: the international system, the individual states, and institutions themselves The fall of the iron curtain has created a changed international environment, and the opportunity for European international institutions to extend their membership, to alter and enhance their roles, and to influence the politics of their members. The EU has sought to project economic security through trade, and to exercise a political and diplomatic role beyond its borders. During the cold war, the allies on both sides of the Atlantic relied upon national defence and NATO to protect their territories. With the end of the cold war, both NATO and the EU were inevitably forced to re-examine their roles and raison d’être. Within the EC, the process of adaptation was different, as member states first wanted to consolidate their existing policy programme, including EMU

H-Diplo roundtable XXIII-32 on Nationalism and After: With a New Introduction from Michael Cox

E.H. Carr. Nationalism and After: With a New Introduction from Michael Cox. London: Palgrave Macmillan, 2021. ISBN: 978-1-349-96037-8 (softcover, $29.99)

Acute Exercise and Appetite-Regulating Hormones in Overweight and Obese Individuals: A Meta-Analysis

In lean individuals, acute aerobic exercise is reported to transiently suppress sensations of appetite, suppress blood concentrations of acylated ghrelin (AG), and increase glucagon-like peptide-1 (GLP-1) and peptide-YY (PYY). Findings in overweight/obese individuals have yet to be synthesised. In this systematic review and meta-analysis, we quantified the effects that acute exercise has on AG and total PYY and GLP-1 in overweight/obese individuals. The potential for body mass index (BMI) to act as a moderator for AG was also explored. Six published studies (73 participants, 78% male, mean BMI: 30.6 kg⋅m −2 ) met the inclusion criteria. Standardised mean differences (SMDs) and standard errors were extracted for AG and total PYY and GLP-1 concentrations in control and exercise trials and synthesised using a random effects meta-analysis model. BMI was the predictor in metaregression for AG. Exercise moderately suppressed AG area-under-the-curve concentrations (pooled SMD: −0.34, 95% CI: −0.53 to −0.15). The magnitude of this reduction was greater for higher mean BMIs (pooled metaregression slope: −0.04 SMD/kg⋅m −2 (95% CI: −0.07 to 0.00)). Trivial SMDs were obtained for total PYY (0.10, 95% CI: −0.13 to 0.31) and GLP-1 (−0.03, 95% CI: −0.18 to 0.13). This indicates that exercise in overweight/obese individuals moderately alters AG in a direction that could be associated with decreased hunger and energy intake. This trial is registered with PROSPERO: CRD42014006265

Predicting the Risk of Rheumatoid Arthritis and Its Age of Onset through Modelling Genetic Risk Variants with Smoking

The improved characterisation of risk factors for rheumatoid arthritis (RA) suggests they could be combined to identify individuals at increased disease risks in whom preventive strategies may be evaluated. We aimed to develop an RA prediction model capable of generating clinically relevant predictive data and to determine if it better predicted younger onset RA (YORA). Our novel modelling approach combined odds ratios for 15 four-digit/10 two-digit HLA-DRB1 alleles, 31 single nucleotide polymorphisms (SNPs) and ever-smoking status in males to determine risk using computer simulation and confidence interval based risk categorisation. Only males were evaluated in our models incorporating smoking as ever-smoking is a significant risk factor for RA in men but not women. We developed multiple models to evaluate each risk factor's impact on prediction. Each model's ability to discriminate anti-citrullinated protein antibody (ACPA)-positive RA from controls was evaluated in two cohorts: Wellcome Trust Case Control Consortium (WTCCC: 1,516 cases; 1,647 controls); UK RA Genetics Group Consortium (UKRAGG: 2,623 cases; 1,500 controls). HLA and smoking provided strongest prediction with good discrimination evidenced by an HLA-smoking model area under the curve (AUC) value of 0.813 in both WTCCC and UKRAGG. SNPs provided minimal prediction (AUC 0.660 WTCCC/0.617 UKRAGG). Whilst high individual risks were identified, with some cases having estimated lifetime risks of 86%, only a minority overall had substantially increased odds for RA. High risks from the HLA model were associated with YORA (P<0.0001); ever-smoking associated with older onset disease. This latter finding suggests smoking's impact on RA risk manifests later in life. Our modelling demonstrates that combining risk factors provides clinically informative RA prediction; additionally HLA and smoking status can be used to predict the risk of younger and older onset RA, respectively

Clinical Utility of Random Anti–Tumor Necrosis Factor Drug–Level Testing and Measurement of Antidrug Antibodies on the Long-Term Treatment Response in Rheumatoid Arthritis

Objective: To investigate whether antidrug antibodies and/or drug non-trough levels predict the long-term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions.  Methods: A total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme-linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non-trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated.  Results: Among patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody–positive patients received lower median dosages of methotrexate compared with antidrug antibody–negative patients (15 mg/week versus 20 mg/week; P = 0.01) and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of ≥30 kg/m2 and poor adherence were associated with lower drug levels.  Conclusion: Pharmacologic testing in anti–tumor necrosis factor–treated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months

La Grande-Bretagne et la communauté économique européenne (1958-1963)

[eng] Abstract The difficulties, which Britain had to face when she wanted to join the EEC, have their roots in the shortcomings of her European policy since 1945 ; «atlanticist» and hostile to supra-national organisations, the British were not attracted by the plans for European integration, and they withdrew from the Messina conference (november 1955). The Free Trade area project was intended as an engine of war against the EEC, but it failed in that respect and EFTA rather became a burden to Britain. Negotiations for a rapprochement of CEE and EFTA were brought to a halt by General de Gaulle's first veto (november 1958), a forgotten, but significant episode. In 1959-60, H.M.G. and Whitehall made a thorough reassessment of british policy (specially through the «Lee committee»). This led to the application for entry into the EEC in July 1961, but its timing and form were rather clumsy. The decision belonged to de Gaulle, whom the British vainly tried to coax by offering some «nuclear bargain». They were in a weak position and not properly supported by the U.S.A. Actually, de Gaulle had decided to veto the british application, before the Kennedy-Macmillan encounter in Nassau. The author is critical of British diplomacy, its procrastination and its illusions. [fre] Résumé Les difficultés auxquelles s'est heurtée la Grande-Bretagne, quand elle a voulu entrer dans la CEE ont leurs origines dans les déficiences de sa politique européenne depuis 1945 ; «atlantique», hostile à la supra-nationalité, elle a été réticente devant les projets de construction européenne, elle s'est retirée de la conférence de Messine en 1955. Elle a lancé en vain le projet de zone de libre-échange comme machine de guerre contre la CEE, mais cette organisation a été en fait un fardeau pour elle. Les négociations pour rapprocher AELE et CEE se terminèrent par un premier veto du Général de Gaulle, en novembre 1958, qui est oublié, mais fut important. Le gouvernement de Londres procéda ensuite à un réexamen approfondi de sa position (notamment par le «Comité Lee»). Cette réflexion aboutit à la demande d'adhésion à la CEE en juillet 1961, mais celle-ci fut faite maladroitement et à un moment mal choisi. Tout dépendait du Général de Gaulle, mais les Britanniques ne réussirent pas à l'amadouer par l'offre d'un «marché nucléaire». Ils se trouvaient en position de faiblesse, mal soutenus en plus par les États-Unis. Avant même l'entrevue Kennedy- Macmillan à Nassau, de Gaulle avait décidé de mettre son «veto». L'auteur est sévère pour la diplomatie britannique, ses atermoiements, ses illusions.