Dual mechanism of brain injury and novel treatment strategy in maple syrup urine disease

Maple syrup urine disease (MSUD) is an inherited disorder of branched-chain amino acid metabolism presenting with lifethreatening cerebral oedema and dysmyelination in affected individuals. Treatment requires life-long dietary restriction and monitoring of branched-chain amino acids to avoid brain injury. Despite careful management, children commonly suffer metabolic decompensation in the context of catabolic stress associated with non-specific illness. The mechanisms underlying this decompensation and brain injury are poorly understood. Using recently developed mouse models of classic and intermediate maple syrup urine disease, we assessed biochemical, behavioural and neuropathological changes that occurred during encephalopathy in these mice. Here, we show that rapid brain leucine accumulation displaces other essential amino acids resulting in neurotransmitter depletion and disruption of normal brain growth and development. A novel approach of administering norleucine to heterozygous mothers of classic maple syrup urine disease pups reduced branched-chain amino acid accumulation in milk as well as blood and brain of these pups to enhance survival. Similarly, norleucine substantially delayed encephalopathy in intermediate maple syrup urine disease mice placed on a high protein diet that mimics the catabolic stress shown to cause encephalopathy in human maple syrup urine disease. Current findings suggest two converging mechanisms of brain injury in maple syrup urine disease including: (i) neurotransmitter deficiencies and growth restriction associated with branchedchain amino acid accumulation and (ii) energy deprivation through Krebs cycle disruption associated with branched-chain ketoacid accumulation. Both classic and intermediate models appear to be useful to study the mechanism of brain injury and potential treatment strategies for maple syrup urine disease. Norleucine should be further tested as a potential treatment to prevent encephalopathy in children with maple syrup urine disease during catabolic stress

OmniDepth: Dense Depth Estimation for Indoors Spherical Panoramas.

Recent work on depth estimation up to now has only focused on projective images ignoring 360o content which is now increasingly and more easily produced. We show that monocular depth estimation models trained on traditional images produce sub-optimal results on omnidirectional images, showcasing the need for training directly on 360o datasets, which however, are hard to acquire. In this work, we circumvent the challenges associated with acquiring high quality 360o datasets with ground truth depth annotations, by re-using recently released large scale 3D datasets and re-purposing them to 360o via rendering. This dataset, which is considerably larger than similar projective datasets, is publicly offered to the community to enable future research in this direction. We use this dataset to learn in an end-to-end fashion the task of depth estimation from 360o images. We show promising results in our synthesized data as well as in unseen realistic images

Hydraulics of skimming flows on stepped chutes: The effects of inflow conditions?

Modern stepped spillways are typically designed for large discharge capacities corresponding to a skimming flow regime for which flow resistance is predominantly form drag. The writer demonstrates that the inflow conditions have some effect on the skimming flow properties. Boundary layer calculations show that the flow properties at inception of free-surface aeration are substantially different with pressurized intake. The re-analysis of experimental results highlights that the equivalent Darcy friction factor is f similar to 0.2 in average on uncontrolled stepped Chute and f similar to 0.1 on stepped chute with pressurized intake. A simple design chart is presented to estimate the residual flow velocity, and the agreement of the calculations with experimental results is deemed satisfactory for preliminary design

A finite model of two-dimensional ideal hydrodynamics

A finite-dimensional su($N$) Lie algebra equation is discussed that in the infinite $N$ limit (giving the area preserving diffeomorphism group) tends to the two-dimensional, inviscid vorticity equation on the torus. The equation is numerically integrated, for various values of $N$, and the time evolution of an (interpolated) stream function is compared with that obtained from a simple mode truncation of the continuum equation. The time averaged vorticity moments and correlation functions are compared with canonical ensemble averages.Comment: (25 p., 7 figures, not included. MUTP/92/1

Adult women and ADHD: on the temporal dimensions of ADHD identities

This paper uses conceptual resources drawn psychosocial process thinking (Stenner, 2017, Brown and Reavey, 2015, Brown and Stenner, 2009) and from G.H. Mead in particular, to contribute to an emerging body of work on the experiences of adult women with ADHD (Singh, 2002, Waite and Ivey, 2009, Quinn and Madhoo, 2014, Horton-Salway and Davies, 2018). It has a particular focus on how ADHD features in the construction of women’s identities and life-stories and it draws upon findings from a qualitative investigation of adult women diagnosed or self-diagnosed with Attention Deficit Hyperactivity Disorder (ADHD). A theoretically informed ‘thematic decomposition’ of 16 depth interviews reveals how complex processes of identity transformation are mediated by the social category of ADHD. Through this process, pasts are reconstructed from the perspective of an ‘emergent’ identity that offers participants the potential for a more enabling and positive future