Spinal muscular atrophy: Factors that modulate motor neurone vulnerability.

Spinal muscular atrophy (SMA), a leading genetic cause of infant death, is a neurodegenerative disease characterised by the selective loss of particular groups of motor neurones in the anterior horn of the spinal cord with concomitant muscle weakness. To date, no effective treatment is available, however, there are ongoing clinical trials are in place which promise much for the future. However, there remains an ongoing problem in trying to link a single gene loss to motor neurone degeneration. Fortunately, given successful disease models that have been established and intensive studies on SMN functions in the past ten years, we are fast approaching the stage of identifying the underlying mechanisms of SMA pathogenesis Here we discuss potential disease modifying factors on motor neurone vulnerability, in the belief that these factors give insight into the pathological mechanisms of SMA and therefore possible therapeutic targets

Swarm-based adaptation: wayfinding support for lifelong learners

Please refer to the orinigal publication in: Tattersall, C. Van den Berg, B., Van Es, R., Janssen, J., Manderveld, J., Koper, R. (2004). Swarm-based adaptation: wayfinding support for lifelong learners. In P. de Bra & W. Nejdl, Adaptive Hypermedia and Adaptive Web-Based Systems (LNCS3137), (pp. 336-339). Heidelberg: Springer. http://www.springerlink.com/index/UW0DUG7KHTU0KBX9.This article introduces an approach to adaptive wayfinding support for lifelong learners based on self-organisation theory. It describes an architecture which supports the recording, processing and presentation of collective learner behaviour designed to create a feedback loop informing learners of successful paths towards the attainment of their learning objectives. The approach is presented as an alternative to methods of achieving adaptation in hypermedia-based learning environments which involve learner modelling

A semantical approach to equilibria and rationality

Game theoretic equilibria are mathematical expressions of rationality. Rational agents are used to model not only humans and their software representatives, but also organisms, populations, species and genes, interacting with each other and with the environment. Rational behaviors are achieved not only through conscious reasoning, but also through spontaneous stabilization at equilibrium points. Formal theories of rationality are usually guided by informal intuitions, which are acquired by observing some concrete economic, biological, or network processes. Treating such processes as instances of computation, we reconstruct and refine some basic notions of equilibrium and rationality from the some basic structures of computation. It is, of course, well known that equilibria arise as fixed points; the point is that semantics of computation of fixed points seems to be providing novel methods, algebraic and coalgebraic, for reasoning about them.Comment: 18 pages; Proceedings of CALCO 200

Local volume fraction distributions of axons, astrocytes, and myelin in deep subcortical white matter

This study aims to statistically describe histologically stained white matter brain sections to subsequently inform and validate diffusion MRI techniques. For the first time, we characterise volume fraction distributions of three of the main structures in deep subcortical white matter (axons, astrocytes, and myelinated axons) in a representative cohort of an ageing population for which well-characterized neuropathology data is available. We analysed a set of samples from 90 subjects of the Cognitive Function and Ageing Study (CFAS), stratified into three groups of 30 subjects each, in relation to the presence of age-associated deep subcortical lesions. This provides volume fraction distributions in different scenarios relevant to brain diffusion MRI in dementia. We also assess statistically significant differences found between these groups. In agreement with previous literature, our results indicate that white matter lesions are related with a decrease in the myelinated axons fraction and an increase in astrocytic fraction, while no statistically significant changes occur in axonal mean fraction. In addition, we introduced a framework to quantify volume fraction distributions from 2D immunohistochemistry images, which is validated against in silico simulations. Since a trade-off between precision and resolution emerged, we also performed an assessment of the optimal scale for computing such distributions

Optical band edge shift of anatase cobalt-doped titanium dioxide

We report on the optical properties of magnetic cobalt-doped anatase phase titanium dioxide Ti_{1-x}Co_{x}O_{2-d} films for low doping concentrations, 0 <= x <= 0.02, in the spectral range 0.2 to 5 eV. For well oxygenated films (d << 1) the optical conductivity is characterized by an absence of optical absorption below an onset of interband transitions at 3.6 eV and a blue shift of the optical band edge with increasing Co concentration. The absence of below band gap absorption is inconsistent with theoretical models which contain midgap magnetic impurity bands and suggests that strong on-site Coulomb interactions shift the O-band to Co-level optical transitions to energies above the gap.Comment: 5 pages, 4 figures, 1 table; Version 2 - major content revisio

Axonal Preservation in Deep Subcortical White Matter Lesions in the Ageing Brain

Cerebral white matters lesions (WML) are seen in 94% of the population aged 64 and over and are associated with cognitive decline and depression. We used immunohistochemistry and stereological methods on post mortem brain samples derived from the Medical Research Council Cognitive Function and Ageing Study (MRC-CFAS) cohort to investigate the axonal density within deep subcortical lesions. There was no significant difference between the lesional and control white matter, therefore, we conclude that there is axonal preservation within these lesions that are characterized by demyelination

Competition of charge, orbital, and ferromagnetic correlations in layered manganites

The competition of charge, orbital, and ferromagnetic interactions in layered manganites is investigated by magneto-Raman scattering spectroscopy. We find that the colossal magnetoresistance effect in the layered compounds results from the interplay of the orbital and ferromagnetic double-exchange correlations. Inelastic scattering by charge-order fluctuations dominates the quasiparticle dynamics in the ferromagnetic-metal state. The scattering is suppressed at low frequencies, consistent with the opening of a charge-density wave pseudogap.Comment: 10 pages, 4 figure

Bulk experimental evidence of half-metallic ferromagnetism in doped manganites

We report precise measurements and quantitative data analysis on the low-temperature resistivity of several ferromagnetic manganite films. We clearly show that there exists a T^{4.5} term in low-temperature resistivity, and that this term is in quantitative agreement with the quantum theory of two-magnon scattering for half metallic ferromagnets. Our present results provide the first bulk experimental evidence of half-metallic ferromagnetism in doped manganites.Comment: 4 pages, 4 figure

Effectiveness and cost-effectiveness of daily all-over-body application of emollient during the first year of life for preventing atopic eczema in high-risk children (The BEEP trial): protocol for a randomised controlled trial.

BACKGROUND: Atopic eczema (AE) is a common skin problem that impairs quality of life and is associated with the development of other atopic diseases including asthma, food allergy and allergic rhinitis. AE treatment is a significant cost burden for health care providers. The purpose of the trial is to investigate whether daily application of emollients for the first year of life can prevent AE developing in high-risk infants (first-degree relative with asthma, AE or allergic rhinitis). METHODS: This is a protocol for a pragmatic, two-arm, randomised controlled, multicentre trial. Up to 1400 term infants at high risk of developing AE will be recruited through the community, primary and secondary care in England. Participating families will be randomised in a 1:1 ratio to receive general infant skin-care advice, or general skin-care advice plus emollients with advice to apply daily to the infant for the first year of life. Families will not be blinded to treatment allocation. The primary outcome will be a blinded assessment of AE at 24 months of age using the UK Working Party Diagnostic Criteria for Atopic Eczema. Secondary outcomes are other definitions of AE, time to AE onset, severity of AE (EASI and POEM), presence of other allergic diseases including food allergy, asthma and hay fever, allergic sensitisation, quality of life, cost-effectiveness and safety of the emollients. Subgroup analyses are planned for the primary outcome according to filaggrin genotype and the number of first-degree relatives with AE and other atopic diseases. Families will be followed up by online and postal questionnaire at 3, 6, 12 and 18 months with a face-to-face visit at 24 months. Long-term follow-up until 60 months will be via annual questionnaires. DISCUSSION: This trial will demonstrate whether skin-barrier enhancement through daily emollient for the first year of life can prevent AE from developing in high-risk infants. If effective, this simple and cheap intervention has the potential to result in significant cost savings for health care providers throughout the world by preventing AE and possibly other associated allergic diseases. TRIAL REGISTRATION: ISRCTN registry; ID: ISRCTN21528841 . Registered on 25 July 2014