AChR deficiency due to ε-subunit mutations: Two common mutations in the Netherlands

Congenital myasthenic syndromes are a clinically and genetically heterogeneous group of hereditary disorders affecting neuromuscular transmission. We have identified mutations within the acetylcholine receptor (AChR) ε-subunit gene underlying congenital myasthenic syndromes in nine patients (seven kinships) of Dutch origin. Previously reported mutations ε1369delG and εR311Q were found to be common; ε1369delG was present on at least one allele in seven of the nine patients, and εR311Q in six. Phenotypes ranged from relatively mild ptosis and external ophthalmoplegia to generalized myasthenia. The common occurrence of εR311Q and ε1369delG suggests a possible founder for each of these mutations originating in North Western Europe, possibly in Holland. Knowledge of the ethnic or geographic origin within Europe of AChR deficiency patients can help in targeting genetic screening and it may be possible to provide a rapid genetic diagnosis for patients of Dutch origin by screening first for εR311Q and ε1369delG

Colorectal liver metastases: Surgery versus thermal ablation (COLLISION) - a phase III single-blind prospective randomized controlled trial

Background: Radiofrequency ablation (RFA) and microwave ablation (MWA) are widely accepted techniques to eliminate small unresectable colorectal liver metastases (CRLM). Although previous studies labelled thermal ablation inferior to surgical resection, the apparent selection bias when comparing patients with unresectable disease to surgical candidates, the superior safety profile, and the competitive overall survival results for the more recent reports mandate the setup of a randomized controlled trial. The objective of the COLLISION trial is to prove non-inferiority of thermal ablation compared to hepatic resection in patients with at least one resectable and ablatable CRLM and no extrahepatic disease. Methods: In this two-arm, single-blind multi-center phase-III clinical trial, six hundred and eighteen patients with at least one CRLM (≤3cm) will be included to undergo either surgical resection or thermal ablation of appointed target lesion(s) (≤3cm). Primary endpoint is OS (overall survival, intention-to-treat analysis). Main secondary endpoints are overall disease-free survival (DFS), time to progression (TTP), time to local progression (TTLP), primary and assisted technique efficacy (PTE, ATE), procedural morbidity and mortality, length of hospital stay, assessment of pain and quality of life (QoL), cost-effectiveness ratio (ICER) and quality-adjusted life years (QALY). Discussion: If thermal ablation proves to be non-inferior in treating lesions ≤3cm, a switch in treatment-method may lead to a reduction of the post-procedural morbidity and mortality, length of hospital stay and incremental costs without compromising oncological outcome for patients with CRLM. Trial registration:NCT03088150 , January 11th 2017

Experimental realization of superconducting quantum interference devices with topological insulator junctions

We demonstrate topological insulator (Bi2Te3) dc SQUIDs, based on superconductingNb leads coupled to nano-fabricated Nb-Bi2Te3-Nb Josephson junctions. The high reproducibility and controllability of the fabrication process allow the creation of dc SQUIDs with parameters that are in agreement with design values. Clear critical current modulation of both the junctions and the SQUID with applied magnetic fields have been observed. We show that the SQUIDs have a periodicity in the voltage-flux characteristic of Φ0 of relevance to the ongoing pursuit of realizing interferometers for the detection of Majorana fermions in superconductor—topological insulator structures

Experimental realization of superconducting quantum interference devices with topological insulator junctions

We demonstrate topological insulator (Bi2Te3) dc SQUIDs, based on superconductingNb leads coupled to nano-fabricated Nb-Bi2Te3-Nb Josephson junctions. The high reproducibility and controllability of the fabrication process allow the creation of dc SQUIDs with parameters that are in agreement with design values. Clear critical current modulation of both the junctions and the SQUID with applied magnetic fields have been observed. We show that the SQUIDs have a periodicity in the voltage-flux characteristic of Φ0 of relevance to the ongoing pursuit of realizing interferometers for the detection of Majorana fermions in superconductor—topological insulator structures