NEXMIF encephalopathy: an X-linked disorder with male and female phenotypic patterns

Item does not contain fulltextPURPOSE: Pathogenic variants in the X-linked gene NEXMIF (previously KIAA2022) are associated with intellectual disability (ID), autism spectrum disorder, and epilepsy. We aimed to delineate the female and male phenotypic spectrum of NEXMIF encephalopathy. METHODS: Through an international collaboration, we analyzed the phenotypes and genotypes of 87 patients with NEXMIF encephalopathy. RESULTS: Sixty-three females and 24 males (46 new patients) with NEXMIF encephalopathy were studied, with 30 novel variants. Phenotypic features included developmental delay/ID in 86/87 (99%), seizures in 71/86 (83%) and multiple comorbidities. Generalized seizures predominated including myoclonic seizures and absence seizures (both 46/70, 66%), absence with eyelid myoclonia (17/70, 24%), and atonic seizures (30/70, 43%). Males had more severe developmental impairment; females had epilepsy more frequently, and varied from unaffected to severely affected. All NEXMIF pathogenic variants led to a premature stop codon or were deleterious structural variants. Most arose de novo, although X-linked segregation occurred for both sexes. Somatic mosaicism occurred in two males and a family with suspected parental mosaicism. CONCLUSION: NEXMIF encephalopathy is an X-linked, generalized developmental and epileptic encephalopathy characterized by myoclonic-atonic epilepsy overlapping with eyelid myoclonia with absence. Some patients have developmental encephalopathy without epilepsy. Males have more severe developmental impairment. NEXMIF encephalopathy arises due to loss-of-function variants

The origins of Odense – new aspects of early urbanisation in southern Scandinavia

The article presents an updated study of the centuries prior to Odense’s traditional ‘birth certificate’ of AD 988, resulting in a new model for the urbanisation of Odense. The conclusion reached is that there was activity of a permanent and possibly urban character in Odense from the end of the late eighth century until the late tenth century. The town’s development can be followed through three phases. Phases 1 and 2 cover the periods AD 700–900 and AD 900–100, respectively, while phase 3 covers the period AD 1000-1101. During phases 1 and 2, the proto-town develops through bottomup processes, such as network, crafts and possibly trade. After AD 1000, Odense develops into a town proper, under royal influence. The model from Odense provides the background for a fresh view of urbanisation in southern Scandinavia in general. A three-phase model is proposed. Phase 0 constitutes the emporia of the eighth–ninth century, which perhaps primarily is satellites in a trading network controlled from the south. Phase 1 takes the form of locally initiated and based incipient urbanisation extending from the end of the eighth century until the tenth century. Phase 2 comprises the royally established towns from around AD 1000 onwards

Gas gain stabilisation in the ATLAS TRT detector

International audienceThe ATLAS (one of two general purpose detectors at the LHC) Transition Radiation Tracker (TRT) is the outermost of the three tracking subsystems of the ATLAS Inner Detector. It is a large straw-based detector and contains about 350,000 electronics channels. The performance of the TRT as tracking and particularly particle identification detector strongly depends on stability of the operation parameters with most important parameter being the gas gain which must be kept constant across the detector volume. The gas gain in the straws can vary significantly with atmospheric pressure, temperature, and gas mixture composition changes. This paper presents a concept of the gas gain stabilisation in the TRT and describes in detail the Gas Gain Stabilisation System (GGSS) integrated into the Detector Control System (DCS). Operation stability of the GGSS during Run-1 is demonstrated

Alzheimer's disease risk polymorphisms regulate gene expression in the ZCWPW1 and the CELF1 loci

10.1371/journal.pone.0148717PLoS ONE112e014871

The ATLAS TRT barrel detector

The ATLAS TRT barrel is a tracking drift chamber using 52,544 individual tubular drift tubes. It is one part of the ATLAS Inner Detector, which consists of three sub-systems: the pixel detector spanning the radius range 4 to 20 cm, the semiconductor tracker (SCT) from 30 to 52 cm, and the transition radiation tracker (TRT) from 56 to 108 cm. The TRT barrel covers the central pseudo-rapidity region |h| < 1, while the TRT endcaps cover the forward and backward eta regions. These TRT systems provide a combination of continuous tracking with many measurements in individual drift tubes (or straws) and of electron identification based on transition radiation from fibers or foils interleaved between the straws themselves. This paper describes the recentlycompleted construction of the TRT Barrel detector, including the quality control procedures used in the fabrication of the detecto

The ATLAS Transition Radiation Tracker (TRT) proportional drift tube: design and performance

A straw proportional counter is the basic element of the ATLAS Transition Radiation Tracker (TRT). Its detailed properties as well as the main properties of a few TRT operating gas mixtures are described. Particular attention is paid to straw tube performance in high radiation conditions and to its operational stability