Clinical and genetic delineation of autosomal recessive and dominant ACTL6B-related developmental brain disorders

Purpose: This study aims to comprehensively delineate the phenotypic spectrum of ACTL6B-related disorders, previously associated with both autosomal recessive and autosomal dominant neurodevelopmental disorders. Molecularly, the role of the nucleolar protein ACTL6B in contributing to the disease has remained unclear. Methods: We identified 105 affected individuals, including 39 previously reported cases, and systematically analyzed detailed clinical and genetic data for all individuals. Additionally, we conducted knockdown experiments in neuronal cells to investigate the role of ACTL6B in ribosome biogenesis. Results: Biallelic variants in ACTL6B are associated with severe-to-profound global developmental delay/intellectual disability, infantile intractable seizures, absent speech, autistic features, dystonia, and increased lethality. De novo monoallelic variants result in moderate-to-severe global developmental delay/intellectual disability, absent speech, and autistic features, whereas seizures and dystonia were less frequently observed. Dysmorphic facial features and brain abnormalities, including hypoplastic corpus callosum, and parenchymal volume loss/atrophy, are common findings in both groups. We reveal that in the nucleolus, ACTL6B plays a crucial role in ribosome biogenesis, particularly in pre-rRNA processing. Conclusion: This study provides a comprehensive characterization of the clinical spectrum of both autosomal recessive and dominant forms of ACTL6B-associated disorders. It offers a comparative analysis of their respective phenotypes provides a plausible molecular explanation and suggests their inclusion within the expanding category of “ribosomopathies.”<p/

Lawvere-Tierney sheafification in Homotopy Type Theory

International audienceSheafification is a popular tool in topos theory which allows to extend the internal logic of a topos with new principles. One of its most famous applications is the possibility to transform a topos into a boolean topos using the dense topology, which corresponds in essence to Gödel's double negation translation. The same construction has not been developed in Martin-Löf type theory because of a mismatch between topos theory and type theory. This mismatch has been fixed recently by considering homotopy type theory, an extension of Martin-Löf type theory with new principles inspired by category theory and homotopy theory, and which corresponds closely to higher toposes. In this paper, we give a computer-checked construction of Lawvere-Tierney sheafification in homotopy type theory

Telenephrology and on-site nephrology: Comparable adequate dialysis care to patients living in remote Pacific Islands

Introduction End-stage renal disease is a major public health concern in New Caledonia and in Wallis and Futuna (prevalence value: 2542 per million population in 2017). Spread over the territory, 594 dialysis patients are followed up by nephrologists and partially by telemedicine due to the distance. The aim of our this study was to evaluate the quality of care provided by telemedicine for chronic dialysis patients on Wallis Island, a dialysis unit remote from Noumea (2100 km). Methods We compared two populations of haemodialysis patients, one based in Poindimie in New Caledonia and followed by monthly physical consultation, the other based on Wallis Island and followed by monthly teleconsultation and quarterly on-site consultation. Results From January 2012–December 2017, dialysis adequacy and survival data were recorded for 84 patients: 44 in Poindimie, 40 on Wallis Island. Dialysis adequacy (i.e. clinical, biological parameters) as well as occurrence of vascular access complications were no different regardless of the means of follow-up. During the study, 23 deaths occurred (11 in Poindimie, 12 on Wallis Island; p = 0.464). We did not find any difference in survival at one and six years ( p = 0.46) between the two dialysis units. Evaluation for transplantation was lower for Wallisian patients ( p = 0.042), without impact on the number of patients being transplanted ( p = 0.678). Conclusion Telemedicine is a valuable opportunity for the follow-up of remote chronic haemodialysis patients, allowing them to be treated close to home while ensuring optimal quality of care </jats:sec

Low-field electromagnetic tracking using 3D magnetometer for assisted surgery

International audienceThis article describes an alternative to high-field electromagnetic tracking system, by using low consumption generator and high-performance magnetic sensors. Monotonically varying magnetic fields over three positions are created to produce magnetic field gradients, which encode each spatial point uniquely. Millimetric size sensors capable of measuring their local magnetic field with high resolution are used to sense the gradient field. Such sensors can be embedded in surgical tools, such as catheters or brain electrodes. With a low power consumption and low-field generator, the integrability of the electromagnetic system in a surgical theater is greatly enhanced. This system leads to unambiguous and orientation-independent spatial encoding with a mean absolute error of 3 mm at 42 cm from the field generator using the last generation 3-D axis magnetoresistive sensors. A calibration of the sensors was performed and leads to significant improvement in the localization over the Z -axis