The EU Global Strategy: going beyond effective multilateralism? EPC Discussion Paper, June 2016

The ongoing consultation process on the European Union Global Strategy (EUGS) presents an occasion for the European Union (EU) to redress the European Security Strategy’s (ESS) shortcomings and update its stance on multilateralism. As rule-based multilateralism remains deeply entrenched in the Union’s DNA, the EUGS is unlikely to represent ground-breaking innovations as to how the EU should act in international affairs. The key challenge in respect of the EU’s multilateralism is twofold. The first challenge lies in setting out clear priorities for the EU’s multilateral action to be pursued collectively by the member states; and the second in determining the form of multilateralism that would best suit the promotion of the priorities concerned. In this collection of six essays, policy analysts and academics are presented with the question: Over a five year horizon, what do you think should be the focus of the EU’s multilateral agenda? The answers dwell on the EU playing a proactive role in relation to emerging powers especially China, and Latin America as a whole; furthering the EU’s soft power through ‘science diplomacy’; and EU leadership in building a global energy and climate community, and counter terrorism measures

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p < 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p < 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p < 0.0001) or urgent (20.4% vs. 38.5%; p < 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p < 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

Burden of ventricular arrhythmias at 12-lead 24-hour ambulatory ECG monitoring in middle-aged endurance athletes versus sedentary controls

Background: Whether prolonged and intense exercise increases the incidence of ventricular arrhythmias in middle-aged athletes remains to be established. Design: Prospective, case-control. Methods: We studied 134 healthy competitive athletes >30 years old (median age 45 (39\u201351) years, 83% males) who had been engaged in 9 \ub1 2 h per week of endurance sports activity (running, cycling, triathlon) for 13 \ub1 4 consecutive years. One hundred and thirty-four age- and gender-matched individuals served as controls. Both groups underwent 12-lead 24-h ambulatory electrocardiogram monitoring, which included a training session in athletes. Ventricular arrhythmias were evaluated in terms of number, complexity (i.e. couplet, triplet or non-sustained ventricular tachycardia), exercise-inducibility and morphology. Results: Thirty-five (26%) athletes and 31 (23%) controls showed >10 isolated premature ventricular beats or 651 complex ventricular arrhythmia (p = 0.53). Athletes with ventricular arrhythmias were older (median 48 versus 43 years old, p = 0.03) but did not differ with regard to hours of training and years of activity compared with athletes without ventricular arrhythmias. Ten (7%) athletes and six (5%) controls showed >500 premature ventricular beats/24 h (p = 0.30): the most common ventricular arrhythmia morphologies were infundibular (six athletes and five controls) and fascicular (two athletes and one control). Conclusions: The prevalence of ventricular arrhythmias at 24-hour ambulatory electrocardiogram monitoring did not differ between middle-aged athletes and sedentary controls and was unrelated to the amount and duration of exercise. These findings do not support the hypothesis that endurance sports activity increases the burden of ventricular arrhythmias. Among individuals with frequent premature ventricular beats, the predominant ectopic QRS morphologies were consistent with the idiopathic and benign nature of the arrhythmia

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

Correction: Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

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