Delineating the phenotypic spectrum of Bainbridge-Ropers syndrome: 12 new patients with de novo, heterozygous, loss-of-function mutations in ASXL3 and review of published literature

BACKGROUND: Bainbridge-Ropers syndrome (BRPS) is a recently described developmental disorder caused by de novo truncating mutations in the additional sex combs like 3 (ASXL3) gene. To date, there have been fewer than 10 reported patients. OBJECTIVES: Here, we delineate the BRPS phenotype further by describing a series of 12 previously unreported patients identified by the Deciphering Developmental Disorders study. METHODS: Trio-based exome sequencing was performed on all 12 patients included in this study, which found a de novo truncating mutation in ASXL3. Detailed phenotypic information and patient images were collected and summarised as part of this study. RESULTS: By obtaining genotype:phenotype data, we have been able to demonstrate a second mutation cluster region within ASXL3. This report expands the phenotype of older patients with BRPS; common emerging features include severe intellectual disability (12/12), poor/ absent speech (12/12), autistic traits (9/12), distinct face (arched eyebrows, prominent forehead, high-arched palate, hypertelorism and downslanting palpebral fissures), (9/12), hypotonia (12/12) and significant feeding difficulties (12) when young. DISCUSSION: Similarities in the patients reported previously in comparison with this cohort included their distinctive craniofacial features, feeding problems, absent/limited speech and intellectual disability. Shared behavioural phenotypes include autistic traits, hand-flapping, rocking, aggressive behaviour and sleep disturbance. CONCLUSIONS: This series expands the phenotypic spectrum of this severe disorder and highlights its surprisingly high frequency. With the advent of advanced genomic screening, we are likely to identify more variants in this gene presenting with a variable phenotype, which this study will explore

Oblique triangular antiferromagnetic phase in CsCu1−x_{1-x}Cox_xCl3_3

The spin-1/2 stacked triangular antiferromagnet CsCu$_{1-x}$Co$_x$Cl$_3$ with $0.015<x<0.032$ undergoes two phase transitions at zero field. The low-temperature phase is produced by the small amount of Co$^{2+}$ doping. In order to investigate the magnetic structures of the two ordered phases, the neutron elastic scattering experiments have been carried out for the sample with $x\approx 0.03$. It is found that the intermediate phase is identical to the ordered phase of CsCuCl$_3$, and that the low-temperature phase is an oblique triangular antiferromagnetic phase in which the spins form a triangular structure in a plane tilted from the basal plane. The tilting angle which is 42$^{\circ}$ at $T=1.6$ K decreases with increasing temperature, and becomes zero at $T_{\rm N2} =7.2$ K. An off-diagonal exchange term is proposed as the origin of the oblique phase.Comment: 6 pages, 7 figure

Allostatic self-efficacy: a metacognitive theory of dyshomeostasis-induced fatigue and depression

This paper outlines a hierarchical Bayesian framework for interoception, homeostatic/allostatic control, and meta-cognition that connects fatigue and depression to the experience of chronic dyshomeostasis. Specifically, viewing interoception as the inversion of a generative model of viscerosensory inputs allows for a formal definition of dyshomeostasis (as chronically enhanced surprise about bodily signals, or, equivalently, low evidence for the brain's model of bodily states) and allostasis (as a change in prior beliefs or predictions which define setpoints for homeostatic reflex arcs). Critically, we propose that the performance of interoceptive-allostatic circuitry is monitored by a metacognitive layer that updates beliefs about the brain's capacity to successfully regulate bodily states (allostatic self-efficacy). In this framework, fatigue and depression can be understood as sequential responses to the interoceptive experience of dyshomeostasis and the ensuing metacognitive diagnosis of low allostatic self-efficacy. While fatigue might represent an early response with adaptive value (cf. sickness behavior), the experience of chronic dyshomeostasis may trigger a generalized belief of low self-efficacy and lack of control (cf. learned helplessness), resulting in depression. This perspective implies alternative pathophysiological mechanisms that are reflected by differential abnormalities in the effective connectivity of circuits for interoception and allostasis. We discuss suitably extended models of effective connectivity that could distinguish these connectivity patterns in individual patients and may help inform differential diagnosis of fatigue and depression in the future

Relative drifts and biases between six ozone limb satellite measurements from the last decade

As part of European Space Agency’s (ESA) climate change initiative, high vertical resolution ozone profiles from three instruments all aboard ESA’s Envisat (GOMOS, MIPAS, SCIAMACHY) and ESA’s third party missions (OSIRIS, SMR, ACE-FTS) are to be combined in order to create an essential climate variable data record for the last decade. A prerequisite before combining data is the examination of differences and drifts between the data sets. In this paper, we present a detailed analysis of ozone profile differences based on pairwise collocated measurements, including the evolution of the differences with time. Such a diagnosis is helpful to identify strengths and weaknesses of each data set that may vary in time and introduce uncertainties in long-term trend estimates. The analysis reveals that the relative drift between the sensors is not statistically significant for most pairs of instruments. The relative drift values can be used to estimate the added uncertainty in physical trends. The added drift uncertainty is estimated at about 3% decade$^{-1}$ (1σ). Larger differences and variability in the differences are found in the lowermost stratosphere (below 20 km) and in the mesosphere

Fresnel polarisation of infra-red radiation by elemental bismuth

We revisit the classical problem of electromagnetic wave refraction from a lossless dielectric to a lossy conductor, where both media are considered to be non-magnetic, linear, isotropic and homogeneous. We derive the Fresnel coefficients of the system and the Poynting vectors at the interface, in order to compute the reflectance and transmittance of the system. We use a particular parametrisation of the referred Fresnel coefficients so as to make a connection with the ones obtained for refraction by an interface between two lossless media. This analysis allows the discussion of an actual application, namely the Fresnel polarisation of infra-red radiation by elemental bismuth, based on the concept of pseudo Brewster’s angle.We acknowledge helpful discussions with M. Vasilevskiy, P. Alpuim, J. Caridad and B. Figueiredo. The authors thank the European Structural and Investment Funds in the FEDER component, through the Operational Programme for Competitiveness and Internationalization (COMPETE 2020) [under the Project GNESIS -Graphenest's New Engineered System and its Implementation Solutions; Funding Reference: POCI-01-0247-FEDER-033566], European Regional Development Fund. This work was also supported by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding UID/FIS/04650/2019

Movement in low gravity environments (MoLo) programme The Molo-L.O.O.P. study protocol

The aim of this paper is to define an experimental protocol and methodology suitable to estimate in high-fidelity hypogravity conditions the lower limb internal joint reaction forces. State-of-the-art movement kinetics, kinematics, muscle activation and muscle-tendon unit behaviour during locomotor and plyometric movements will be collected and used as inputs (Objective 1), with musculoskeletal modelling and an optimisation framework used to estimate lower limb internal joint loading (Objective

Metal enrichment processes

There are many processes that can transport gas from the galaxies to their environment and enrich the environment in this way with metals. These metal enrichment processes have a large influence on the evolution of both the galaxies and their environment. Various processes can contribute to the gas transfer: ram-pressure stripping, galactic winds, AGN outflows, galaxy-galaxy interactions and others. We review their observational evidence, corresponding simulations, their efficiencies, and their time scales as far as they are known to date. It seems that all processes can contribute to the enrichment. There is not a single process that always dominates the enrichment, because the efficiencies of the processes vary strongly with galaxy and environmental properties.Comment: 18 pages, 8 figures, accepted for publication in Space Science Reviews, special issue "Clusters of galaxies: beyond the thermal view", Editor J.S. Kaastra, Chapter 17; work done by an international team at the International Space Science Institute (ISSI), Bern, organised by J.S. Kaastra, A.M. Bykov, S. Schindler & J.A.M. Bleeke

Phenomenology of the Lense-Thirring effect in the Solar System

Recent years have seen increasing efforts to directly measure some aspects of the general relativistic gravitomagnetic interaction in several astronomical scenarios in the solar system. After briefly overviewing the concept of gravitomagnetism from a theoretical point of view, we review the performed or proposed attempts to detect the Lense-Thirring effect affecting the orbital motions of natural and artificial bodies in the gravitational fields of the Sun, Earth, Mars and Jupiter. In particular, we will focus on the evaluation of the impact of several sources of systematic uncertainties of dynamical origin to realistically elucidate the present and future perspectives in directly measuring such an elusive relativistic effect.Comment: LaTex, 51 pages, 14 figures, 22 tables. Invited review, to appear in Astrophysics and Space Science (ApSS). Some uncited references in the text now correctly quoted. One reference added. A footnote adde

Gamma rays from colliding winds of massive stars

Colliding winds of massive binaries have long been considered as potential sites of non-thermal high-energy photon production. This is motivated by the detection of non-thermal spectra in the radio band, as well as by correlation studies of yet unidentified EGRET gamma-ray sources with source populations appearing in star formation regions. This work re-considers the basic radiative processes and its properties that lead to high energy photon production in long-period massive star systems. We show that Klein-Nishina effects as well as the anisotropic nature of the inverse Compton scattering, the dominating leptonic emission process, likely yield spectral and variability signatures in the gamma-ray domain at or above the sensitivity of current or upcoming gamma ray instruments like GLAST-LAT. In addition to all relevant radiative losses, we include propagation (such as convection in the stellar wind) as well as photon absorption effects, which a priori can not be neglected. The calculations are applied to WR140 and WR147, and predictions for their detectability in the gamma-ray regime are provided. Physically similar specimen of their kind like WR146, WR137, WR138, WR112 and WR125 may be regarded as candidate sources at GeV energies for near-future gamma-ray experiments. Finally, we discuss several aspects relevant for eventually identifying this source class as a gamma-ray emitting population. Thereby we utilize our findings on the expected radiative behavior of typical colliding wind binaries in the gamma-ray regime as well as its expected spatial distribution on the gamma-ray sky