Novel form of rhizomelic skeletal dysplasia associated with a homozygous variant in GNPNAT1

Background Studies exploring molecular mechanisms underlying congenital skeletal disorders have revealed novel regulators of skeletal homeostasis and shown protein glycosylation to play an important role. Objective To identify the genetic cause of rhizomelic skeletal dysplasia in a consanguineous Pakistani family. Methods Clinical investigations were carried out for four affected individuals in the recruited family. Whole genome sequencing (WGS) was completed using DNA from two affected and two unaffected individuals from the family. Sequencing data were processed, filtered and analysed. In silico analyses were performed to predict the effects of the candidate variant on the protein structure and function. Small interfering RNAs (siRNAs) were used to study the effect of Gnpnat1 gene knockdown in primary rat chondrocytes. Results The patients presented with short stature due to extreme shortening of the proximal segments of the limbs. Radiographs of one individual showed hip dysplasia and severe platyspondyly. WGS data analyses identified a homozygous missense variant c.226G>A; p.(Glu76Lys) in GNPNAT1, segregating with the disease. Glucosamine 6-phosphate N-acetyltransferase, encoded by the highly conserved gene GNPNAT1, is one of the enzymes required for synthesis of uridine diphosphate N-acetylglucosamine, which participates in protein glycosylation. Knockdown of Gnpnat1 by siRNAs decreased cellular proliferation and expression of chondrocyte differentiation markers collagen type 2 and alkaline phosphatase, indicating that Gnpnat1 is important for growth plate chondrocyte proliferation and differentiation. Conclusions This study describes a novel severe skeletal dysplasia associated with a biallelic, variant in GNPNAT1. Our data suggest that GNPNAT1 is important for growth plate chondrogenesis.Peer reviewe

AORTA: Advanced Offloading for Real-time Applications

We are currently witnessing the second wave of cloud services that go beyond web storefronts and IT systems, aiming for digitalization of industrial systems. Automation and time-sensitive systems are now taking their first steps toward the cloud. The AORTA project aims to facilitate this transition by providing key technology components needed for real-time services running in the cloud. The ambition is to support a future robotics ecosystem that enables a new level of flexible productivity in industrial production. AORTA will develop technologies that allow offloading of real-time services/functions to the edge and cloud. We will build upon recent advances in 5G, cloud, and networking technologies. The AORTA framework will support a fluid compute model where functionality will be dynamically deployed locally, in the edge, or in the cloud and support integration and real-time performance irrespective of where it executes. Results of the project will be demonstrated in a real-world robotics manufacturing and construction scenarios operating via a 5G network with real-time edge and large-scale cloud service. The AORTA technologies will provide opportunities for automation enterprises and system integrators by adding real-time capabilities needed to evolve beyond the currently closed ecosystem. They will also add value to telecom providers and operators that may host these new automation services in addition to their current portfolio

Chlorinated and brominated polycyclic aromatic hydrocarbons in ambient air: seasonal variation, profiles, potential sources, and size distribution

Chlorinated and brominated polycyclic aromatic hydrocarbons (ClPAHs and BrPAHs, respectively) are a new derivative group of PAHs. These halogenated PAHs (Halo-PAHs) have been reported to be carcinogenic and are considered emerging persistent organic pollutants. Gaining a clear understanding of the distribution and behavior of these ubiquitous organic pollutants is essential for the control and mitigation of their emission into the environment. However, research into the characteristics of Halo-PAHs in the atmosphere has been somewhat limited. This review paper thus aims to provide an overview of the seasonal patterns, profiles, potential sources, and particle-size distributions of atmospheric ClPAHs and BrPAHs with 3-5 rings. Most previous studies have focused on particulate Halo-PAHs and reported that their levels are higher during the cold season than during the warm season, with this seasonal variation more apparent for ClPAHs than for BrPAHs. In terms of their phase distribution, ClPAHs and BrPAHs share a similar trend, with their gaseous concentrations highest in summer and lowest in winter and their particulate concentrations exhibiting the opposite trend. Halo-PAH profiles have been shown to differ between sampling locations, possibly reflecting differences in the potential sources present at these sites, e.g., coal burning, traffic emissions, and industrial activity. The majority of Halo-PAHs tend to accumulate as ultrafine particles with an aerodynamic diameter of less than 1.0 mu m. Overall, a detailed understanding of the characteristics of Halo-PAHs in the atmosphere has yet to be achieved; hence, further research on atmospheric Halo-PAHs is necessary

A technique to train new oculomotor behavior in patients with central macular scotomas during reading related tasks using scanning laser ophthalmoscopy: immediate functional benefits and gains retention

BACKGROUND: Reading with a central scotoma involves the use of preferred retinal loci (PRLs) that enable both letter resolution and global viewing of word. Spontaneously developed PRLs however often privilege spatial resolution and, as a result, visual span is commonly limited by the position of the scotoma. In this study we designed and performed the pilot trial of a training procedure aimed at modifying oculomotor behavior in subjects with central field loss. We use an additional fixation point which, when combined with the initial PRL, allows the fulfillment of both letter resolution and global viewing of words. METHODS: The training procedure comprises ten training sessions conducted with the scanning laser ophthalmoscope (SLO). Subjects have to read single letters and isolated words varying in length, by combining the use of their initial PRL with the one of an examiner's selected trained retinal locus (TRL). We enrolled five subjects to test for the feasibility of the training technique. They showed stable maculopathy and persisting major reading difficulties despite previous orthoptic rehabilitation. We evaluated ETDRS visual acuity, threshold character size for single letters and isolated words, accuracy for paragraphed text reading and reading strategies before, immediately after SLO training, and three months later. RESULTS: Training the use of multiple PRLs in patients with central field loss is feasible and contributes to adapt oculomotor strategies during reading related tasks. Immediately after SLO training subjects used in combination with their initial PRL the examiner's selected TRL and other newly self-selected PRLs. Training gains were also reflected in ETDRS acuity, threshold character size for words of different lengths and in paragraphed text reading. Interestingly, subjects benefited variously from the training procedure and gains were retained differently as a function of word length. CONCLUSION: We designed a new procedure for training patients with central field loss using scanning laser ophthalmoscopy. Our initial results on the acquisition of newly self-selected PRLs and the development of new oculomotor behaviors suggest that the procedure aiming primarily at developing an examiner's selected TRL might have initiated a more global functional adaptation process

Enhanced text spacing improves reading performance in individuals with macular disease

The search by many investigators for a solution to the reading problems encountered by individuals with no central vision has been long and, to date, not very fruitful. Most textual manipulations, including font size, have led to only modest gains in reading speed. Previous work on spatial integrative properties of peripheral retina suggests that 'visual crowding' may be a major factor contributing to inefficient reading. Crowding refers to the fact that juxtaposed targets viewed eccentrically may be difficult to identify. The purpose of this study was to assess the combined effects of line spacing and word spacing on the ability of individuals with age-related macular degeneration (ARMD) to read short passages of text that were printed with either high (87.5%) or low contrast (17.5%) letters. Low contrast text was used to avoid potential ceiling effects and to mimic a possible reduction in letter contrast with light scatter from media opacities. For both low and high contrast text, the fastest reading speeds we measured were for passages of text with double line and double word spacing. In comparison with standard single spacing, double word/line spacing increased reading speed by approximately 26% with high contrast text (p < 0.001), and by 46% with low contrast text (p < 0.001). In addition, double line/word spacing more than halved the number of reading errors obtained with single spaced text. We compare our results with previous reading studies on ARMD patients, and conclude that crowding is detrimental to reading and that its effects can be reduced with enhanced text spacing. Spacing is particularly important when the contrast of the text is reduced, as may occur with intraocular light scatter or poor viewing conditions. We recommend that macular disease patients should employ double line spacing and double-character word spacing to maximize their reading efficiency. © 2013 Blackmore-Wright et al

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

Modelling of the effect of ELMs on fuel retention at the bulk W divertor of JET

Effect of ELMs on fuel retention at the bulk W target of JET ITER-Like Wall was studied with multi-scale calculations. Plasma input parameters were taken from ELMy H-mode plasma experiment. The energetic intra-ELM fuel particles get implanted and create near-surface defects up to depths of few tens of nm, which act as the main fuel trapping sites during ELMs. Clustering of implantation-induced vacancies were found to take place. The incoming flux of inter-ELM plasma particles increases the different filling levels of trapped fuel in defects. The temperature increase of the W target during the pulse increases the fuel detrapping rate. The inter-ELM fuel particle flux refills the partially emptied trapping sites and fills new sites. This leads to a competing effect on the retention and release rates of the implanted particles. At high temperatures the main retention appeared in larger vacancy clusters due to increased clustering rate