Vagus nerve stimulation for intractable epilepsy: a review

Electrical stimulation of the vagus nerve in the neck by using a programmable stimulator similar to a cardiac pacemaker is being explored as a treatment for epilepsy. There is sound rationale based on studies of animal seizure models for pursuing this treatment modality, and early clinical trials provide support for efficacy in patients with intractable epilepsy at least equivalent to that of some of the new antiepileptic drugs. Safety and tolerability have been demonstrated in >800 patients worldwide since the first implant in 1988. Most of these had partial seizures for which resective epilepsy surgery was not feasible or had failed, but efficacy of vagal stimulation appears to be the same for both partial and generalized epilepsy. Specific selection criteria for this procedure have yet to be established, and further studies are warranted to determine whether vagal stimulation becomes an accepted procedure for epilepsy management.     

Pressure infiltration of boron nitride preforms with molten aluminum

The infiltration of compacted cubic BN (cBN) with molten aluminum has been investigated as a potential route for a cheap and easy method of manufacturing cBN/metal composites. CBN compacts have been infiltrated with molten Al at a temperature between 670 and 800 °C and pressure of 15 MPa in vacuum. At these temperatures no pronounced interactions between hexagonal and cubic BN with Al was observed, allowing the complete infiltration of cBN with 12 μm mean grain size. After infiltration at 800 °C, the temperature was increased without pressure to convert aluminum into borides and AlN. The hardness of the resulting materials depends on the content of hexagonal, cubic BN and the rate of conversion of Al into borides and AlN. The infiltration height of less than 1 mm obtained from infiltrating the 3 μm cBN powder green compacts gave a hardness of 22.0 ± 0.6 GPa after heat treatment.     

N-particle dynamics of the Euler equations for planar diffeomorphisms

The Euler equations associated with diffeomorphism groups have received much recent study because of their links with fluid dynamics, computer vision, and mechanics. In this article, we consider the dynamics of N point particles or “blobs” moving under the action of the Euler equations associated with the group of diffeomorphisms of the plane in a variety of different metrics. This dynamical system is already in widespread use in the field of image registration, where the point particles correspond to image landmarks, but its dynamical behavior has not previously been studied. The 2-body problem is always integrable, and we analyze its phase portrait under different metrics. In particular, we show that 2-body capturing orbits (in which the distances between the particles tend to 0 as t  → ∞) can occur when the kernel is sufficiently smooth and the relative initial velocity of the particles is sufficiently large. We compute the dynamics of these “dipoles” with respect to other test particles, and supplement the calculations with simulations for larger N that illustrate the different regimes.     

Periodic dynamics of coupled cell networks I: rigid patterns of synchrony and phase relations

It has recently been proved by Golubitsky and coworkers that in any network of coupled dynamical systems, the possible 'rigid' patterns of synchrony of hyperbolic equilibria are determined by purely combinatorial properties of the network, known as 'balanced equivalence relations'. A pattern is 'rigid' if it persists under small 'admissible' perturbations of the differential equation — ones that respect the network structure. We discuss a natural generalisation of these ideas to time-periodic states, and motivate two basic conjectures, the Rigid Synchrony Conjecture and the Rigid Phase Conjecture. These conjectures state that for rigid hyperbolic time-periodic patterns, cells with synchronous dynamics must have synchronous input cells, and cells with phase-related dynamics must have input cells that have the same phase relations. We provide evidence supporting the two conjectures, by proving them for a special class of periodic orbits, which we call 'tame', under strong assumptions on the network architecture and the symmetries of the periodic state. The discussion takes place in the formal setting of coupled cell networks. We prove that rigid patterns of synchrony are balanced, together with the analogous result for rigid patterns of phase relations. The assumption on the network architecture simplifies the geometry of admissible vector fields, while tameness rules out patterns with non-trivial local or multilocal symmetry. The main idea is to perturb an admissible vector field in a way that retains sufficient control over the associated perturbed periodic orbit. We present two techniques for constructing these perturbations, both using a general theorem on groupoid-symmetrisation of vector fields, which has independent interest. In particular we introduce a method of 'patching' that makes local changes to an admissible vector field. Having established these results for all-to-all coupled networks and tame periodic orbits we prove more general versions that require these assumptions only on a suitable quotient network. These conditions are weaker and encompass a larger class of networks and periodic orbits. We give an example to show that rigidity cannot be relaxed to hyperbolicity. We also prove, without any technical assumptions, that rigidly synchronous or phase-related cells must be input-isomorphic, a necessary precondition for the two conjectures to hold.     

d-Tubocurarine accentuates the burn-induced upregulation of nicotinic acetylcholine receptors at the muscle membrane

BACKGROUND: Increases in acetylcholine receptors (AChRs) at the muscle membrane, induced by burn injury, have been associated with a hyperkalemic response to succinylcholine and resistance to d-tubocurarine-like drugs. Muscle relaxants often are administered to burn-injured patients in the intensive care unit to facilitate mechanical ventilation. This study in rats tested whether continuous administration of d-tubocurarine in subparalytic doses exaggerates the upregulation of AChRs induced by burn trauma. Subparalytic doses were used to avoid the confounding effects of immobilization. METHODS: Three days after an approximate 50% body surface area burn or sham injury, the animals received an infusion of 3.03 +/- 0.05 micrograms/h of d-tubocurarine or equal volume of saline directly to the left gastrocnemius muscle via catheter connected to a subcutaneously implanted osmotic pump. After 7 days of d-tubocurarine or saline infusion, the AChRs were quantitated using 125I-alpha-bungarotoxin. The AChRs on the d-tubocurarine or saline-infused left gastrocnemius were compared to the contralateral gastrocnemius in the same group. The right or left gastrocnemius AChRs were compared to the ipsilateral muscles between groups. These intra- and intergroup comparisons allowed the delineation of the effects of catheter irritation, burns, or d-tubocurarine on AChRs. RESULTS: Daily examination of the withdrawal response to toe-pinch revealed no evidence of paralysis. Weight loss in the burn-injury animals receiving d-tubocurarine or saline was similar, confirming that the infusion of d-tubocurarine did not impair the mobility of the animals to move and feed. The plasma d-tubocurarine concentration after 7 days of infusion was 26.0 +/- 12 ng/ml (mean +/- SE). Regardless of burn or sham injury or of d-tubocurarine or saline infusion, the concentration of AChRs on the left was consistently greater than in the contralateral right gastrocnemius muscles within the same group, indicating that manipulation of the area alone can result in upregulation of AChRs. The AChRs in the right gastrocnemius of burn-injured animals were greater than those in the same muscle of sham-injured animals, regardless of saline (7.24 +/- 0.9 vs. 5.7 +/- 0.5 fmoles/mg protein, P = 0.06) or d-tubocurarine (7.3 +/- 0.4 vs. 5.7 +/- 0.5, P < 0.05) infusion to the burn-injury groups. AChRs in the left gastrocnemius of burn-injury animals receiving d-tubocurarine were significantly greater than those in burn- or sham-injury animals receiving saline (13.9 +/- 1.1 vs. 9.8 +/- 1.2 and 7.1 +/- 0.5 fmoles/mg protein, respectively, P < 0.05). CONCLUSIONS: Burn-induced upregulation of AChRs is accentuated by infusion of subparalytic doses of d-tubocurarine. Concomitant administration of d-tubocurarine to burn-injured patients may result in further exaggeration of the aberrant responses to neuromuscular relaxants.     

Diverse Fab specific for acetylcholine receptor epitopes from a myasthenia gravis thymus combinatorial library

The muscle weakness in myasthenia gravis (MG) is caused by heterogeneous high-affinity IgG autoantibodies to the nicotinic acetylcholine receptor (AChR), a complex ion channel glycoprotein. These antibodies are clearly responsible for reducing AChR numbers at the neuromuscular junction in myasthenia; however, the origins, diversity, specificity and pathogenicity of individual antibodies have not yet been established. We have cloned and characterized four different AChR-specific Fab from an MG patient's thymus by screening an IgG1/kappa gene combinatorial lambda phage library with soluble human AChR labeled with [125I] alpha-bungarotoxin. Unlike most previously cloned human antibodies, all four Fab immunoprecipitated soluble human muscle AChR. Two Fab strongly inhibited binding of mAb to the main immunogenic region on the alpha subunits and one Fab bound to an epitope on the fetal-specific gamma subunit. In sensitivity and fine specificity, these Fab resembled the anti-AChR antibodies found in many MG patients, including the donor. The closest germline counterparts for their heavy chains were in VH families 1, 3 and 4; however, there were many differences consistent with an antigen-driven response of diverse B cell clones. The combinatorial approach holds promise for further analysis of human autoantibodies.     

Effect of nutrient seed coating on the emergence of wheat and oats

A series of experiments was conducted under controlled soil moisture and temperature conditions in a growth chamber to examine the effect of a range of nutrient seed coatings on the emergence to wheat (Triticum aestivum L. cv. Kite) and oats (Avena sativa L. cv. Blackbutt) sown in a coarse sandy loam soil. Final emergence of oats was not reduced by a coating containing 10 kg P ha^–1 (as monocalcium phosphate [MCP]) whereas the same coating reduced wheat emergence by 15%. The emergence of both wheat and oats was severely reduced by urea coatings (supplying 10 kg N ha^–1) to 33 and 13% respectively; this injury was lessened markedly by the inclusion of phenyl phosphorodiamidate (PPD) in the urea coatings at 1% (w/w) (emergence increased to 66 and 56% respectively).Low soil moisture (67% of field capacity [FC]) resulted in almost no emergence of wheat coated with urea (± bentonites of different pH). In soil at FC, the addition of bentonite of pH 5 (B5) to urea coatings permitted greater emergence (54%) than when bentonite of pH 9 (B9) was added (32%) which, in turn, permitted greater emergence than urea coating alone (10%). When PPD and bentonite (B5 or B9) were combined either singly or together with urea in seed coatings, PPD was more effective than either of the bentonites in reducing injury and masked the slight positive effect of B5.Coatings containing various combinations of N and P sources (at 3.6 and at 8 kg ha^–1 respectively) all reduced the emergence of wheat compared to raw seed (91% emergence). When applied alone, MCP was least damaging (74%); the combination of MCP with ammonium sulfate (AS) caused somewhat more injury (68%) whilst combination with calcium nitrate (CN) caused most injury (29%). In contrast, CN alone caused relatively little damage (73%) whilst AS alone was more damaging (50%). There was no significant regression found between percentage emergence and either the calculated partial salt index or the pH of the nutrient coatings. Further work is needed to examine the mechanisms of injury due to nutrient seed coatings so that safe but effective formulations can be developed.     

Study of the volume fraction,temperature, and pressure dependence of the resistivity in a ceramic-polymer composite using a general effective media theory equation

A quantitative general effective media (GEM) equation is used to describe quantitatively the resistivity of an Fe₃O₄-epoxy composite system over a large range of volume fractions in terms of the resistivities of each component and two percolation morphology parameters. One parameter is the critical (percolation) volume fraction, _c, and the other is an exponent,t. Preliminary models, also based on the GEM equation, are used to describe the positive temperature coefficient of resistivity (PTC) and the piezoresistivity (uniaxial pressure) of the composite when the composition is near the percolation threshold.     

The Inhibition of Geographical Information in Digital Humanities Scholarship

Information about place and location is an essential part ofresearch in the humanities. There are many ways that methodsand tools for structuring, visualizing and analysing space,spatial behaviour, and spatial relationships can benefit humanitiesresearch but the use of spatial information in digital scholarshipby humanists remains very limited. The developing role of thestudy of place and location through geographical informationsystems (GIS) and other digital tools is discussed briefly beforeexamining the factors that are inhibiting the use of spatialdata in our research. The influences of current research practiceand the attitudes of scholarly institutions in the humanitiesare examined. This article will explore some of the potentialresearch applications but, possibly more importantly; it willalso examine why that potential is being developed so slowlyand discuss a possible way forward for the community.