Development of multi-electrode array screening for anticonvulsants in acute rat brain slices

The acute hippocampal brain slice preparation is an important in vitro screening tool for potential anticonvulsants. Application of 4-aminopyridine (4-AP) or removal of external Mg2+ ions induces epileptiform bursting in slices which is analogous to electrical brain activity seen in status epilepticus states. We have developed these epileptiform models for use with multi-electrode arrays (MEAs), allowing recording across the hippocampal slice surface from 59 points. We present validation of this novel approach and analyses using two anticonvulsants, felbamate and phenobarbital, the effects of which have already been assessed in these models using conventional extracellular recordings. In addition to assessing drug effects on commonly described parameters (duration, amplitude and frequency), we describe novel methods using the MEA to assess burst propagation speeds and the underlying frequencies that contribute to the epileptiform activity seen. Contour plots are also used as a method of illustrating burst activity. Finally, we describe hitherto unreported properties of epileptiform bursting induced by 100M4-AP or removal of external Mg2+ ions. Specifically, we observed decreases over time in burst amplitude and increase over time in burst frequency in the absence of additional pharmacological interventions. These MEA methods enhance the depth, quality and range of data that can be derived from the hippocampal slice preparation compared to conventional extracellular recordings. It may also uncover additional modes of action that contribute to anti-epileptiform drug effects

Algorithm for generating defective graphene sheets

An algorithm is presented for the generation of molecular models of defective graphene fragments, containing a majority of 6-membered rings with a small number of 5- and 7-membered rings as defects. The structures are generated from an initial random array of points in 2D space, which are then subject to Delaunay triangulation. The dual of the triangulation forms a Voronoi tessellation of polygons with a range of ring sizes. An iterative cycle of refinement, involving deletion and addition of points followed by further triangulation, is performed until the user-defined criteria for the number of defects are met. The array of points and connectivities are then converted to a molecular structure and subject to geometry optimization using a standard molecular modeling package to generate final atomic coordinates. On the basis of molecular mechanics with minimization, this automated method can generate structures, which conform to user-supplied criteria and avoid the potential bias associated with the manual building of structures. One application of the algorithm is the generation of structures for the evaluation of the reactivity of different defect sites. Ab initio electronic structure calculations on a representative structure indicate preferential fluorination close to 5-ring defects.

Field trial using bone meal amendments to remediate mine waste derived soil contaminated with zinc, lead and cadmium

Bone meal amendments are being considered as a remediation method for metal-contaminated wastes. In various forms (biogenic, geogenic or synthetic), apatite, the principal mineral constituent of bone, has shown promise as an amendment to remediate metal-contaminated soils via the formation of insoluble phosphates of Pb and possibly other metals. The efficacy of commercially available bovine bone meal in this role was investigated in a field trial at Nenthead, Cumbria with a mine waste derived soil contaminated with Zn, Pb and Cd. Two 5 m(2) plots were set up: the first as a control and the second, a treatment plot where the soil was thoroughly mixed with bone meal to a depth of 50 cm at a soil to amendment ratio of 25:1 by weight. An array of soil solution samplers (Rhizon SMS (TM)) were installed in both plots and the soil pore water was collected and analysed for Ca, Cd, Zn and Pb regularly over a period of 2 a. Concurrently with the field trial, a laboratory trial with 800 mm high and 100 mm wide leaching Columns Was conducted using identical samplers and with soil from the held site. A substantial release of Zn, Pb, Cd and Ca was observed associated with the bone meal treatment. This release was transient in the case of the leaching columns, and showed seasonal variation in the case of the field trial. It is proposed that this effect resulted from metal complexation with organic acids released during breakdown of the bone meal organic fraction and was facilitated by the relatively high soil pH of 7.6-8.0. Even after this transient release effect had subsided or when incinerated bone meal was substituted in order to eliminate the organic fraction, no detectable decrease in dissolved metals was observed and no P was detected in solution, in contrast with an earlier small column laboratory study. It is concluded that due to the relative insolubility of apatite at above-neutral pH, the rate of supply of phosphate to soil solution was insufficient to result in significant precipitation of metal phosphates and that this may limit the effectiveness of the method to more acidic soils. (c) 2008 Elsevier Ltd. All rights reserved.

The effects of different forms of advice on the control of a simulated complex system

Three experiments examine the effect of different forms of computer-generated advice on concurrent and subsequent performance of individuals controlling a simulated intensive-care task. Experiment 1 investigates the effect of optional and compulsory advice and shows that both result in an improvement in subjects' performance while receiving the advice, and also in an improvement in subsequent unaided performance. However, although the advice compliance displayed by the optional advice group shows a strong correlation with subsequent unaided performance, compulsory advice has no extra benefit over the optional use of advice. Experiment 2 examines the effect of providing users with on-line explanations of the advice, as well as providing less specific advice. The results show that both groups perform at the same level on the task as the advice groups from Experiment 1, although subjects receiving explanations scored significantly higher on a written post-task questionnaire. Experiment 3 investigates in more detail the relationship between advice compliance and performance. The results reveal a complex relationship between natural ability on the task and the following of advice, in that people who use the advice more tend to perform either better or worse than the more moderate users. The theoretical and practical implications of these experiments are discussed.

Generic systolic array for genetic algorithms

The authors present a systolic design for a simple GA mechanism which provides high throughput and unidirectional pipelining by exploiting the inherent parallelism in the genetic operators. The design computes in O(N+G) time steps using O(N2) cells where N is the population size and G is the chromosome length. The area of the device is independent of the chromosome length and so can be easily scaled by replicating the arrays or by employing fine-grain migration. The array is generic in the sense that it does not rely on the fitness function and can be used as an accelerator for any GA application using uniform crossover between pairs of chromosomes. The design can also be used in hybrid systems as an add-on to complement existing designs and methods for fitness function acceleration and island-style population management

Interfacial structure of wild-type and mutant forms of puroindoline-b bound to DPPG monolayers

The interaction of wild-type puroindoline-b (Pin-b+) and two mutant forms having single residue substitutions (G46S or W44R) with L-alpha-dipalmitoylphosphatidyl-dl-glycerol (DPPG) as a Langmuir monolayer at the air/water interface was investigated by neutron reflectivity (NR) and Brewster angle microscopy (BAM). NR profiles were fitted using a three-layer model to enable differences in penetration of protein between the lipid headgroup and acyl regions to be determined. The data showed similar surface excesses for each of the three proteins at the interface; however, it was revealed that the depth of penetration of protein into the lipid region differed for each protein with Pin-b+ penetrating further into the acyl region of the lipid compared to the mutant forms of the protein that interacted with the headgroup region only. BAM images revealed that the domain structure of the DPPG monolayers was disrupted when Pin-b+ adsorption had reached equilibrium, suggesting protein penetration had led to compression of the lipid region. In contrast, the domain structure was unaffected by the W44R mutant, suggesting no change in compression of the lipid region and hence little or no penetration of protein into the lipid layer.

A retrospective audit of medicines use review forms

The medicines use review (MUR) service was introduced in England and Wales in 2005 to improve patients’ knowledge and use of medicines through a private, patient–pharmacist consultation. The pharmacist completes a standard form as a record of the MUR consultation and the patient receives a copy. The 2008 White Paper, Pharmacy in England[1] notes some MURs are of poor or questionable quality and there are anecdotal reports that pharmacists elect to conduct ‘easy’ MURs with patients on a single prescribed medicine only.[2] In 2009, the Royal Pharmaceutical Society of Great Britain (RPSGB) launched a multi-disciplinary audit template to review the effectiveness of MURs and improve their quality.[3] Prior to this, we conducted a retrospective MUR audit in a 1-month period in 2008. Our aims were to report on findings from this audit and the validity of using MUR forms as data for audit.

Children's caring roles and responsibilities within the family in Africa

In many Sub-Saharan African countries, the care of chronically ill, disabled or elderly relatives is usually regarded as the responsibility of family members, within a broader landscape of often overburdened healthcare systems, the expense of medical fees, very limited access to social protection and policies that emphasise home-based care. Recent studies have demonstrated that children and youth, particularly girls and young women, take on considerable caring roles for chronically ill and elderly relatives in Africa. This article reviews the available research on young people’s caring roles and responsibilities within families affected by chronic illness and disability in Sub-Saharan Africa. I discuss how children’s caring roles challenge global and local constructions of childhood and suggest ways of conceptualising the socio-spatial and embodied dimensions of children’s everyday care work within diverse household forms. I analyse evidence on outcomes of care and children’s resilience in managing their caring responsibilities and examine the complex array of processes that influence whether children take on caring roles within the family. I argue that relational, intergenerational and lifecourse approaches to researching children’s caring responsibilities within the family have considerable potential for future geographical research and could provide further insights into the ways that care is embedded in social relations, cultural norms and structural inequalities operating in different configurations in particular places.