High politics in the Low Countries: COVID-19 and the politics of strained multi-level policy cooperation in Belgium and the Netherlands

COVID-19 presented Europe with an, in many respects, unprecedented challenge. While the virus proved itself to be transnational in nature, not taking heed of borders, government responses were largely national. Still, governments soon found themselves engaged in complex multi-level policy cooperation at the national, subnational, and supranational levels. This paper looks at the crisis response in the Low Countries (Belgium and the Netherlands) to understand the impact of this process on the political system. We argue that efficient multi-level policy cooperation in both countries has run up against the limits of existing institutions, leading to significant political grievances. In Belgium, slow negotiation between the central and regional governments has put the federal system in question. In the Netherlands, meanwhile, the absence of European institutions tasked with fiscal policy coordination has increased the salience of the EU fiscal sphere once again

Echocardiographic AV-interval optimization in patients with reduced left ventricular function

BACKGROUND: Ritter's method is a tool used to optimize AV delay in DDD pacemaker patients with normal left ventricular function only. The goal of our study was to evaluate Ritter's method in AV delay-interval optimization in patients with reduced left ventricular function. METHODS: Patients with implanted DDD pacemakers and AVB III° were assigned to one of two groups according to ejection fraction (EF): Group 1 (EF > 35%) and Group 2 (EF < 35%). AV delay optimization was performed by means of radionuclide ventriculography (RNV) and application of Ritter's method. RESULTS: For each of the patients examined, we succeeded in defining an optimal AV interval by means of both RNV and Ritter's method. The optimal AV delay determined by RNV correlated well with the delay found by Ritter's method, especially among those patients with reduced EF. The intra-class correlation coefficient was 0.8965 in Group 1 and 0.9228 in Group 2. The optimal AV interval in Group 1 was 190 ± 28.5 ms, and 180 ± 35 ms in Group 2. CONCLUSION: Ritter's method is also effective for optimization of AV intervals among patients with reduced left ventricular function (EF < 35%). The results obtained by RNV correlate well with those from Ritter's method. Individual programming of the AV interval is fundamentally essential in all cases

Hepatitis C Virus (HCV) Evades NKG2D-Dependent NK Cell Responses through NS5A-Mediated Imbalance of Inflammatory Cytokines

Understanding how hepatitis C virus (HCV) induces and circumvents the host's natural killer (NK) cell-mediated immunity is of critical importance in efforts to design effective therapeutics. We report here the decreased expression of the NKG2D activating receptor as a novel strategy adopted by HCV to evade NK-cell mediated responses. We show that chronic HCV infection is associated with expression of ligands for NKG2D, the MHC class I-related Chain (MIC) molecules, on hepatocytes. However, NKG2D expression is downmodulated on circulating NK cells, and consequently NK cell-mediated cytotoxic capacity and interferon-γ production are impaired. Using an endotoxin-free recombinant NS5A protein, we show that NS5A stimulation of monocytes through Toll-like Receptor 4 (TLR4) promotes p38- and PI3 kinase-dependent IL-10 production, while inhibiting IL-12 production. In turn, IL-10 triggers secretion of TGFβ which downmodulates NKG2D expression on NK cells, leading to their impaired effector functions. Moreover, culture supernatants of HCV JFH1 replicating Huh-7.5.1 cells reproduce the effect of recombinant NS5A on NKG2D downmodulation. Exogenous IL-15 can antagonize the TGFβ effect and restore normal NKG2D expression on NK cells. We conclude that NKG2D-dependent NK cell functions are modulated during chronic HCV infection, and demonstrate that this alteration can be prevented by exogenous IL-15, which could represent a meaningful adjuvant for therapeutic intervention

The immunopathology of ANCA-associated vasculitis.

The small-vessel vasculitides are a group of disorders characterised by variable patterns of small blood vessel inflammation producing a markedly heterogeneous clinical phenotype. While any vessel in any organ may be involved, distinct but often overlapping sets of clinical features have allowed the description of three subtypes associated with the presence of circulating anti-neutrophil cytoplasmic antibodies (ANCA), namely granulomatosis with polyangiitis (GPA, formerly known as Wegener's Granulomatosis), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (eGPA, formerly known as Churg-Strauss syndrome). Together, these conditions are called the ANCA-associated vasculitidies (AAV). Both formal nomenclature and classification criteria for the syndromes have changed repeatedly since their description over 100 years ago and may conceivably do so again following recent reports showing distinct genetic associations of patients with detectable ANCA of distinct specificities. ANCA are not only useful in classifying the syndromes but substantial evidence implicates them in driving disease pathogenesis although the mechanism by which they develop and tolerance is broken remains controversial. Advances in our understanding of the pathogenesis of the syndromes have been accompanied by some progress in treatment, although much remains to be done to improve the chronic morbidity associated with the immunosuppression required for disease control

Vasculitis: a CLEAR argument for targeting complement in ANCA vasculitis

Mechanistic studies have implicated the alternative complement pathway, specifically C5a receptor activation, in the pathogenesis of anti-neutrophil cytoplasmic antibody-associated vasculitis. Results from a phase 2 trial suggest that C5a receptor blockade could enable the reduced use or complete withdrawal of steroids from induction protocols

Ultrasound fetal measurements and pregnancy associated glycoprotein secretion in early pregnancy in cattle recipients carrying somatic clones

Somatic cloning in the bovine species leads to high levels of fetal losses which occur throughout pregnancy. These losses are most often associated with fetal overgrowth, a syndrome known as large offspring syndrome (LOS), and excessive maternal plasma pregnancy serum protein 60 (PSP60), a protein similar to a pregnancy-associated glycoprotein of 67 kDa (PAG 167) produced by the bovine placenta. Predicting the outcome of pregnancies initiated from cloned embryos has become an important issue both to prevent potential harm to the mother because of excessive fetal size at birth and also to get a better understanding of the relationships between growth, differentiation and placental functions in developing cloned fetuses. Here, we report on a systematic analysis of fetal and placental development in the first trimester of pregnancy performed by ultrasonographic imaging and by measurement of the maternal concentrations of pregnancy associated glycoproteins (PAGS), using four different radioimmunoassays (RIA) (two homologous RIA systems with PSP60 and PAG 167; two heterologous RIA systems with PAG 167 as standard and tracer, and antisera anti-caprine PAGs). We showed that crown-rump length (CRL) in clones appeared smaller than controls at 35, 50 and 62 days (P < 0.05). At 62 days of pregnancy, CRL in cloned fetuses that died before 90 days was smaller compared to the other cloned fetuses (P < 0.05) whereas the width of the fetal sack and the biparietal diameter (BPD) was larger in fetuses that developed LOS in late gestation (P < 0.05). Maternal PAGs concentrations were statistically different between controls and all clone recipients as early as Day 34, suggesting early abnormal placental glycoprotein synthesis for clone pregnancies regardless of pregnancy outcome. This work provides a practical, non-invasive tool to follow up clone pregnancies and suggests that primary growth retardation and abnormal placental function precedes excessive fetal and placental growth at later stages of pregnancy. (c) 2006 Elsevier Inc. All rights reserved