The Low Countries in the early Middle Ages. Christianity is on the rise, partly due to the efforts of missionaries such as Willibrord and Boniface. Yet the process of Christianisation is laborious. ...This is well illustrated in Vita Radbodi, a tenth-century Latin biography of bishop Radboud of Utrecht (c. 850-917).In it, Radboud is depicted as a pious, serious and studious young man, who is called to the episcopate after many years of study. As bishop, he encounters problems with unbelieving Frisians and ferocious Normans. Thus, he is forced to move his seat from Utrecht to the safer Deventer.The text offers a positive portrait of Radboud as a holy role model figure. He acts energetically, performs miracles and, of course, also possesses prophetic gifts. For instance, he predicts his own end well in time. The text ends with a vision of the Mother of God and Radboud's death and burial.Some twenty years after the first edition by Peter Nissen and Vincent Hunink, the text is now being reissued on the occasion of Radboud University's centenary.
Platelet aggregation during aspirin treatment displays considerable inter-individual variability. A genetic etiology likely exists, but it remains unclear to what extent genetic polymorphisms ...determine platelet aggregation in aspirin-treated individuals.
To identify platelet-related single nucleotide polymorphisms (SNPs) influencing platelet aggregation during aspirin treatment. Furthermore, we explored to what extent changes in cyclooxygenase-1 activity and platelet activation may explain such influence.
We included 985 Danish patients with stable coronary artery disease treated with aspirin 75 mg/day mono antiplatelet therapy. Patients were genotyped for 16 common SNPs in platelet-related genes using standard PCR-based methods (TaqMan). Platelet aggregation was evaluated by whole blood platelet aggregometry employing Multiplate Analyzer (agonists: arachidonic acid and collagen) and VerifyNow Aspirin. Serum thromboxane B2 was measured to confirm aspirin adherence and was used as a marker of cyclooxygenase-1 activity. Soluble P-selectin was used as marker of platelet activation. Platelet aggregation, cyclooxygenase-1 activity, and platelet activation were compared across genotypes in adjusted analyses.
The A-allele of the rs12041331 SNP in the platelet endothelial aggregation receptor-1 (PEAR1) gene was associated with reduced platelet aggregation and increased platelet activation, but not with cyclooxygenase-1 activity. Platelet aggregation was unaffected by the other SNPs analyzed.
A common genetic variant in PEAR1 (rs12041331) reproducibly influenced platelet aggregation in aspirin-treated patients with coronary artery disease. The exact biological mechanism remains elusive, but the effect of this polymorphism may be related to changes in platelet activation. Furthermore, 14 SNPs previously suggested to influence aspirin efficacy were not associated with on-aspirin platelet aggregation.
ClinicalTrials.gov NCT01383304.
Objective
Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominantly inherited disorder with overlapping biochemistry profile with primary hyperparathyroidism (PHPT), making the correct ...diagnosis a challenge. The objective of the study was to evaluate the results of the clinical work‐up of a large group of hypercalcemic individuals.
Design
Cross‐sectional study.
Patients
Patients undergoing clinical work‐up of hypercalcemia.
Measurements
Molecular genetic analysis of the CASR gene and exon 2 of the AP2S1 gene. Plasma levels of ionized calcium and PTH as well as calcium creatinine clearance ratio (CCCR).
Results
A rare CASR variant was identified in 38 of 624 index patients (6.1%). A total of 18 CASR variants identified in this study were novel. No variants were identified in exon 2 of the AP2S1 gene. The majority of the variants (N = 16) were classified as likely pathogenic. The level of plasma calcium, plasma PTH and the CCCR was not affected by the type of variant (ie nonsense vs missense) (all P‐values >.05). The CCCR was found to be significantly lower for variants in the transmembrane domain compared with variants located in the extracellular domain (P < .05). Plasma levels of calcium and PTH were not associated with the location of the variant (P > .05).
Conclusions
We expanded the spectrum of CASR variants in hypercalcemia with 18 novel variants, and suggest that the location of the CASR variant may affect calcium excretion as determined by the CCCR.
Scalable quantum processors require tunable two-qubit gates that are fast, coherent and long-range. The Heisenberg exchange interaction offers fast and coherent couplings for spin qubits, but is ...intrinsically short-ranged. Here, we demonstrate that its range can be increased by employing a multielectron quantum dot as a mediator, while preserving speed and coherence of the resulting spin-spin coupling. We do this by placing a large quantum dot with 50-100 electrons between a pair of two-electron double quantum dots that can be operated and measured simultaneously. Two-spin correlations identify coherent spin-exchange processes across the multielectron quantum dot. We further show that different physical regimes of the mediated exchange interaction allow a reduced susceptibility to charge noise at sweet spots, as well as positive and negative coupling strengths up to several gigahertz. These properties make multielectron dots attractive as scalable, voltage-controlled coherent coupling elements.
Reduced effect of antiplatelet therapy has been reported in patients with ST-segment elevation myocardial infarction (STEMI). MicroRNAs (miRs) may influence platelet function and maturity, and ...subsequently the effect of antiplatelet therapy.
We aimed to explore the association between miR expression and platelet function and maturity in patients with acute STEMI and healthy individuals.
We performed an observational study of STEMI patients admitted directly to primary percutaneous coronary intervention. Patients were treated with antiplatelet therapy according to guidelines. Within 24 hours after admission, blood samples were obtained to measure: the expression of 10 candidate miRs, platelet function markers using advanced flow cytometry, platelet aggregation, serum thromboxane B
, and platelet maturity markers. Furthermore, blood samples from healthy individuals were obtained to determine the normal variation.
In total, 61 STEMI patients and 50 healthy individuals were included. STEMI patients had higher expression of miR-21-5p, miR-26b-5p, and miR-223-3p and lower expression of miR-150-5p, miR423-5p, and miR-1180-3p than healthy individuals. In STEMI patients, the expression of miR-26b-5p showed the most consistent association with platelet function (all
-values <0.05, Spearman's rho ranging from 0.27 to 0.41), while the expression of miR-150-5p and miR-223-3p showed negative associations with platelet function. No association between miR expression and platelet maturity markers was observed.
In patients with STEMI, the expression of six miRs was significantly different from healthy individuals. The expression of miR-26b-5p may affect platelet function in acute STEMI patients and potentially influence the effect of antiplatelet therapy.
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