bluuebunny/crossref_metadata_2025 huggingface dataset:
Return current and proton emission from short pulse laser interactions with wire targets
Authors: Beg F. N. , Wei M. S. , Clark E. L. , Dangor A. E. , Evans R. G. , Gibbon P. , Gopal A. , Lancaster K. L. , Ledingham K. W. D. , McKenna P. , Norreys P. A. , Tatarakis M. , Zepf M. , Krushelnick K.
Published: April 2004

Results are presented from laser–plasma interaction experiments using the VULCAN laser at the Rutherford Appleton Laboratory. Wire targets were used to elucidate the role of the return currents generated by the relativistic electron beam leaving the target at laser intensities up to 5×1019 W cm−2. For some shots an additional wire or a foil was placed near the target wire. In other shots, a foil was used as the target with a wire behind. Three main observations were made: (i) Z-pinch behavior in the wires due to the return currents, (ii) optical transition radiation (OTR) at the second harmonic of the laser, and (iii) proton emission. The OTR and the proton emission were observed from both the primary wire target and the adjacent wire. The OTR emission is associated with electron bunches at twice the laser frequency due to ponderomotive J×B acceleration by the laser. The proton emission from the adjacent target was likely due to field emission of electrons by the large potential produced from charging of the primary wire target. The observations agree with simulations using the three-dimensional tree code PEPC and the two-and-one-half-dimensional particle-in-cell code OSIRIS.
Simulation of gate-controlled Coulomb blockades in carbon nanotubes
Authors: Feng Y. Q. , Zhang R. Q. , Lee S. T.
Published: April 2004

The electronic transport properties of several nanotubes that are sandwiched between two metallic electrodes and modulated by a gate electrode are studied by a semiclassical approach based on the charging energies and electronic structures determined using ab initio density functional theory. The calculated conductance as a function of the bias and gate voltages shows how the bias and gate voltages control the electronic contribution to the electrical transport in nanotubes. Coulomb blockades and conducting resonances are revealed, and the conductivity of the nanotubes can be judged accordingly. The adjustments of both bias and gate voltages at room temperature can result in various interesting I–V characteristics, including the variable threshold bias voltage and plateau regions of the current, thus providing insight into the design of molecular devices with a variety of logical functions.
Characterization of pedestal parameters and edge localized mode energy losses in the Joint European Torus and predictions for the International Thermonuclear Experimental Reactor
Authors: Loarte A. , Saibene G. , Sartori R. , Eich T. , Kallenbach A. , Suttrop W. , Kempenaars M. , Beurskens M. , de Baar M. , Lönnroth J. , Lomas P. J. , Matthews G. , Fundamenski W. , Parail V. , Becoulet M. , Monier-Garbet P. , de la Luna E. , Gonçalves B. , Silva C. , Corre Y. , Workprogramme Contributors to the EFDA-JET
Published: April 2004

This paper presents the experimental characterization of pedestal parameters, edge localized mode (ELM) energy, and particle losses from the main plasma and the corresponding ELM energy fluxes on plasma facing components for a series of dedicated experiments in the Joint European Torus (JET). From these experiments, it is demonstrated that the simple hypothesis relating the peeling-ballooning linear instability to ELM energy losses is not valid. Contrary to previous observations at lower triangularities, small energy losses at low collisionality have been obtained in regimes at high plasma triangularity and q95∼4.5, indicating that the edge plasma magnetohydrodynamic stability is linked with the transport mechanisms that lead to the loss of energy by conduction during type I ELMs. Measurements of the ELM energy fluxes on the divertor target show that their time scale is linked to the ion transport along the field and the formation of a high energy sheath, in agreement with kinetic modeling of ELMs. Higher density ELMs, of a convective nature, lead to overall much longer time scales for the ELM energy flux, with more than 80% of the ELM energy flux arriving after the surface divertor temperature has reached its maximum value. On the contrary, for low density ELMs, of a conductive nature, up to 40% of the energy flux arrives at the divertor target before the surface divertor temperature has reached its maximum value. These large and more conductive ELMs may lead to up to ∼50% of the ELM energy reaching the main wall plasma facing components instead of the divertor target. The extrapolation to the International Thermonuclear Experimental Reactor of the obtained results is described and the main uncertainties discussed.
Current drive by coaxial helicity injection in a spherical torus
Authors: Tang X. Z. , Boozer A. H.
Published: April 2004

Noninductive current drive by coaxial helicity injection can be understood through the poloidal flux evolution of the toroidally averaged magnetic field B̄0. In the open flux region of B̄0, electrostatic biasing provides an effective loop voltage that overcomes the resistive decay and supports the dynamo loop voltage in the closed flux region via the primary nonaxisymmetric open field line kinks. The current gradient in the closed flux region of B̄0 drives secondary nonaxisymmetric closed flux magnetohydrodynamical modes that facilitate further current relaxation toward the magnetic axis. The decreasing parallel current gradient and high-q magnetic surfaces as one approaches the magnetic axis implies that the eventual current relaxation consistent with magnetic confinement must benefit from a cascade of weaker and comparatively short wavelength modes localized to the high-q resonant home flux surfaces.
Organic thin-film transistors based on anthracene oligomers
Authors: Inoue Youji , Tokito Shizuo , Ito Kaname , Suzuki Toshiyasu
Published: April 2004

Organic thin-film transistors (OTFTs)—with an active layer based on the organic semiconducting anthracene oligomers, 2,2′-bianthracene (2A), 2,6-trianthracene (3A), and their dihexyl derivatives (DH-2A and DH-3A)—were fabricated. It was found that thin films of anthracene oligomers deposited by thermal evaporation had lamellar structures with a high degree of molecular ordering. Consequently, the OTFTs based on anthracene oligomers showed high field-effect mobilities. The mobility of the OTFTs was increased by the oligomerization and the substitution of alkyl groups. DH-2A on a SiO2/Si substrate showed the highest mobility of 0.13 cm2/V s. It was also found that the electrical characteristics of the OTFTs were improved by using a Ta2O5 gate insulator.
Correlations between liquid crystal director reorientation and optical response time of a homeotropic cell
Authors: Wang Haiying , Wu Thomas X. , Zhu Xinyu , Wu Shin-Tson
Published: April 2004

Correlations between the director reorientation time and its consequent optical response time (both decay and rise) of a homeotropic liquid crystal (LC) cell under crossed polarizers are derived theoretically based on small angle approximation. Results indicate that the optical response time is linearly proportional to the LC director reorientation time and is weakly dependent on the initial bias voltage. To validate the derived correlations, transient phase and transmittance responses at various bias voltages are analyzed numerically by solving the Erickson–Leslie equation. Pretilt angle is found to make an important contribution to the optical response time. Gray scale switching of the homeotropic cell is also investigated.
N doping using N2O and NO sources: From the viewpoint of ZnO
Authors: Matsui Hiroaki , Saeki Hiromasa , Kawai Tomoji , Tabata Hitoshi , Mizobuchi Bunsho
Published: April 2004

A study of N doping using N2O and NO sources on ZnO, which may prove important for the N doping of oxide materials, was performed by investigating the doping processes of N atoms by each source together with the various properties for the grown N doped ZnO films. N2O was employed as the radio-frequency (rf) plasma source to produce radical N2* species that could effectively incorporate N atoms above 1020 cm−3 into ZnO, which was similar to N doping using N2 as the source. In contrast, it was found that the ZnO films doped with a N concentration above 1020 cm−3 were easily obtained using a gas flow of NO. The N concentration could be controlled systematically by the simultaneous gas flow of NO and O2 sources. The basis of N doping using a NO source could be related to the free radical characteristic of NO molecular. This idea was proposed from the results that the N concentrations doped to ZnO using a gas flow of N2O and N2, which have the characteristics of neutral and nonreactive molecules in air, were in the ranges from 1018 to 1019 cm−3. Further, our investigations clarified that the structural, optical, and electrical properties for the N doped ZnO films were not quite dependent on the N2, N2O and NO sources used as N dopants. This work proposes that NO is a promising source as a N dopant that can be employed without using a rf plasma source in the application of physical vapor deposition techniques that are indispensable for producing radical N2* species through a rf plasma source to achieve the efficient incorporation of N atoms when N2 and N2O sources are used as N dopants.
Similarity solutions for magnetic bubble expansion
Authors: Finn John M. , Lapenta Giovanni , Li Hui
Published: April 2004

A model for an expanding magnetic bubble or plasmoid is introduced, corresponding to a large aspect ratio torus, having one-dimensional (cylindrical) symmetry but with three dimensional expansion, with the length of the cylinder expanding in time in the same manner as the radius. This model has a general class of similarity equations in ideal magnetohydrodynamics (MHD) for spherical expansion. There are two parameters c, d characterizing the similarity solutions, depending on boundary conditions and conservation relations. These solutions exhibit either tangential discontinuities or shocks at the boundary, depending on the values of the constants c and d. Some of the solutions have magnetic fluxes within the bubble increasing with time, but with smaller or zero magnetic fields outside the bubble, requiring a shock and a dynamo in the shock region. The results of simulations of one class of solutions with a Lagrangian MHD code show good agreement. Some of the properties of fully toroidal solutions of the similarity equations are derived. This model has applications to a magnetic bubble from an accretion disk around an active galactic nucleus (AGN), appropriate to the phase in which the bubble has expanded to a size much greater than the disk field length scales but much smaller than any exterior scales. At this stage the magnetic reconnection and flux conversion stage associated with setting up the expanding bubble is completed. The model may also apply to a plasmoid formed in the solar corona.
Participatory research in dryland cropping systems — monitoring and simulation of soil water and nitrogen in farmers' paddocks in Central Queensland
Authors: Foale M. A. , Probert M. E. , Carberry P. S. , Lack D. , Yeates S. , Brimblecombe D. , R.Shaw  , Crocker M.
Published: April 2004

Collaboration of researchers and service-providers with farmers in addressing crop and soil management, using on-farm experiments and cropping system simulation, was negotiated in 2 districts in Central Queensland, Australia. The 2 most influential variables affecting crop productivity in this region (soil water and mineral nitrogen contents) and the growth of sown crops, were monitored and simulated for 3 years beginning in December 1992. Periodic soil sampling of large experimental strips on 3 farms, from paddocks that differed in cropping history and soil properties, provided robust datasets of change, over time, of soil water and mineral nitrogen status. Farmers participated in twice-yearly discussions with researchers, informed by the accumulating data, which influenced thinking about soil behaviour and possible new management strategies. As the study period coincided with a prolonged drought, so that cropping opportunities were few, the objectives of the work were modified to concentrate almost exclusively on the soil variables.The contribution of the Agricultural Production Systems Simulator, which was used to simulate the measured changes in soil water and mineral nitrogen, was found by all participants to be useful. The APSIM output generally demonstrated close correspondence with field observations, which raised confidence in its applicability to local cropping systems. Exploration of hypothetical situations of interest to farmer participants, in the form of what-if scenarios, provided insights into the behaviour of the production system for a range of soil and seasonal conditions. The informed speculation of the simulator became a substitute for the farmers' own, more tentative, efforts.The regular participative review sessions proved to be highly effective in stimulating the learning of both farmers and researchers. The farmers were able to feel comfortable as owners of the collaborative experiments and custodians of the learning environment. Clear evidence for the ongoing learning of these farmers appeared in post-collaboration practices and experiences.
The economic value of pasture phases in the integrated management of annual ryegrass and wild radish in a Western Australian farming system
Authors: Monjardino M. , Pannell D. J. , Powles S. B.
Published: April 2004

Most cropping farms in Western Australia must deal with the management of herbicide-resistant populations of weeds such as annual ryegrass (Lolium rigidum Gaudin) and wild radish (Raphanus raphanistrum�L.). Farmers are approaching the problem of herbicide resistance by adopting integrated weed management systems, which allow weed control with a range of different techniques. One important question in the design of such systems is whether and when the benefits of including pasture in rotation with crops exceed the costs. In this paper, the multi-species resistance and integrated management model was used to investigate the value of including pasture phases in the crop rotation. The most promising of the systems examined appears to be so-called 'phase farming', involving occasional 3-year phases of pasture rather than shorter, more frequent and regular pasture phases. This approach was competitive with the best continuous cropping rotation in a number of scenarios, particularly where herbicide resistance was at high levels.
Evaluation of the Exposure—Response Relationship of Lung Cancer Mortality and Occupational Exposure to Hexavalent Chromium Based on Published Epidemiological Data
Authors: van Wijngaarden Edwin , Mundt Kenneth A. , Luippold Rose S.
Published: April 2004

Some have suggested a threshold mechanism for the carcinogenicity of exposure to hexavalent chromium, Cr(VI). We evaluated the nature of the exposure—response relationship between occupational exposure to Cr(VI) and respiratory cancer based on results of two recently published epidemiological cohort studies. The combined cohort comprised a total of 2,849 workers employed at two U.S. chromate production plants between 1940 and 1974. Standardized mortality ratios (SMRs) for lung cancer in relation to cumulative Cr(VI) exposure categories were reported using regional mortality rates. Linear additive and multiplicative relative risk regression models were fit to the SMRs of the individual and combined studies. Both models fit the data from the individual studies reasonably well; however, the fit was somewhat less adequate for the pooled data. Meta-analysis of the slope estimates obtained from the multiplicative relative risk model showed substantial heterogeneity between the two epidemiological studies. In conclusion, these data indicate that a linear dose response describes the relationship between Cr(VI) and lung cancer reasonably well, and therefore these analyses do not necessarily support the threshold hypothesis for the lung carcinogenicity of Cr(VI). However, these results must be interpreted with recognition of the limitations of the use of epidemiological data in the evaluation of nonlinear exposure—response patterns.
The C‐peptide Signaling
Authors: Grunberger George , Sima Anders A. F.
Published: April 2004

For years an assumption was made that C‐peptide, a
byproduct of insulin biosynthesis, possessed no appreciable
physiologic role. As other contributions in this volume
amply testify, the time has come to re‐evaluate that notion.
C‐peptide either directly through interaction with its specific
cell‐surface receptor or indirectly through an interaction
with a related membrane entity, exerts a unique effect
on several intracellular processes.We review here results of
studies attempting to elucidate such molecular effects of
C‐peptide in different cell systems and tissues. Lacking a
purified C‐peptide receptor, we also demonstrate C‐peptide
effects on distinct elements of the insulin signal transduction
pathways.
Effects of C‐peptide on Microvascular Blood Flow and Blood Hemorheology
Authors: Forst T. , Kunt T.
Published: April 2004

Beside functional and structural changes in vascular biology,
alterations in the rheologic properties of blood cells
mainly determines to an impaired microvascular blood
flow in patients suffering from diabetes mellitus. Recent
investigations provide increasing evidence that impaired
C‐peptide secretion in type 1 diabetic patients might contribute
to the development of microvascular complications.
C‐peptide has been shown to stimulate endothelial
NO secretion by activation of the Ca2+calmodolin regulated
enzyme eNOS. NO himself has the potency to increase
cGMP levels in smooth muscle cells and to activate
Na+K+ATPase activity and therefore evolves numerous effects
in microvascular regulation. In type 1 diabetic patients,
supplementation of C‐peptide was shown to improve endothelium
dependent vasodilatation in an NO‐dependent
pathway in different vascular compartments. In addition,
it could be shown that C‐peptide administration in type 1
diabetic patients, results in a redistribution of skin blood
flow by increasing nutritive capillary blood flow in favour
to subpapillary blood flow. Impaired Na+K+ATPase in another
feature of diabetes mellitus in many cell types and
is believed to be a pivotal regulator of various cell functions.
C‐peptide supplementation has been shown to restore
Na+K+ATPase activity in different cell types during
in vitro and in vivo investigations. In type 1 diabetic patients,
C‐peptide supplementation was shown to increase
erythrocyte Na+K+ATPase activity by about 100%. There
was found a linear relationship between plasma C‐peptide
levels and erythrocyte Na+K+ATPase activity. In small
capillaries, microvascular blood flow is increasingly determined
by the rheologic properties of erythrocytes. Using laser‐diffractoscopie a huge improvement in erythrocyte deformability
could be observed after C‐peptide administration
in erythrocytes of type 1 diabetic patients. Inhibition
of the Na+K+ATPase by Obain completely abolished the
effect of C‐peptide on erythrocyte deformability. In conclusion,
C‐peptide improves microvascular function and blood
flow in type 1 diabetic patients by interfering with vascular
and rheological components of microvascular blood flow.
Type 1 Diabetic Neuropathy and C‐peptide
Authors: Sima Anders A. F. , Zhang Weixian , Grunberger George
Published: April 2004

The most common microvascular diabetic complication,
diabetic peripheral polyneuropathy (DPN), affects
type 1 diabetic patients more often and more severely.
In recent decades, it has become increasingly clear that
perpetuating pathogenetic mechanisms, molecular, functional,
and structural changes and ultimately the clinical
expression of DPN differ between the two major types of
diabetes. Impaired insulin/C‐peptide action has emerged
as a crucial factor to account for the disproportionate
burden affecting type 1 patients. C‐peptide was long believed
to be biologically inactive. However, it has now
been shown to have a number of insulin‐like glucoseindependent
effects. Preclinical studies have demonstrated
dose‐dependent effects on Na+,K+‐ATPase activity, endothelial
nitric oxide synthase (eNOS), and endoneurial
blood flow. Furthermore, it has regulatory effects on neurotrophic
factors and molecules pivotal to the integrity of
the nodal and paranodal apparatus and modulatory effects
on apoptotic phenomena affecting the diabetic nervous system.
In animal studies, C‐peptide improves nerve conduction
abnormalities, prevents nodal degenerative changes,
characteristic of type 1 DPN, promotes nerve fiber regeneration,
and prevents apoptosis of central and peripheral nerve
cell constituents. Limited clinical trials have confirmed the
beneficial effects of C‐peptide on autonomic and somatic nerve function in patients with type 1 DPN. Therefore, evidence
accumulates that replacement of C‐peptide in type 1
diabetes prevents and even improves DPN. Large‐scale food
and drug administration (FDA)‐approved clinical trials are
necessary to make this natural substance available to the
globally increasing type 1 diabetic population.
What if there are no ‘best practices’?
Authors: Hanushek Eric A.
Published: April 2004

Developing persuasive and consistent models of educational performance has proved elusive. Existing modelling suggests no clear relationship between resources and student performance. This mirrors observed policy outcomes. A possible explanation is that the achievement process is a complicated interactive one such that simple linear additive formulations break down. This analysis presents a stylized model of achievement where unmeasured teacher quality interacts with both resources and specific educational programs. Standard econometric analyses then replicate the aggregate findings in the literature. A policy implication is that finding ‘best practices’ may fail without recognition of the fundamental interactions.
High School Graduation in Australia: Do Schools Matter?
Authors: Le Anh T. , Miller Paul W.
Published: April 2004

This study examines the determinants of high school graduation in Australia. It uses two main approaches to estimation. The first of these is a conventional probit model based on a range of family background and demographic variables. This approach is then extended through consideration of a random parameters probit model. The results show that schools matter to the chances of completing high school in Australia. However, the school effects seem to have more to do with the selection of more able students with superior socioeconomic backgrounds than with the independent creation of favourable school or classroom climates.
The Labour Market Impact of Adult Education and Training: A Cohort Analysis
Authors: Vignoles Anna , Galindo‐Rueda Fernando , Feinstein Leon
Published: April 2004

Education boosts individuals' productivity and wages. Yet many individuals leave school with minimal skills and qualifications. One way for these workers to catch up might be lifelong learning. We find that a particular form of lifelong learning, work related training, does have a positive impact on earnings. However, firms tend only to train those workers who will gain from training. Training does benefit those chosen to receive it but if all workers received training, the average impact on wages would be low. Hence, this form of lifelong learning is not necessarily an effective way of raising wages.
Merger Profitability and Trade Policy
Authors: Huck Steffen , Konrad Kai A.
Published: April 2004

We study the profitability incentives for merger and the endogenous industry structure in a strategic trade policy environment. Merger changes the strategic trade policy equlilibrium. We show that merger can be profitable and welfare enhancing, even though it would not be profitable in a laissez‐faire economy. A key element is a change in the governments’ incentives to give subsidies to their local firms. National merger induces more strategic trade policy, whereas international merger does not.
Ca2+ signalling and gap junction coupling within and between pigment epithelium and neural retina in the developing chick
Authors: Pearson Rachael A. , Catsicas Marina , Becker David L. , Bayley Philippa , Lüneborg Nanna L. , Mobbs Peter
Published: April 2004

Development of the neural retina is controlled in part by the adjacent retinal pigment epithelium (RPE). To understand better the mechanisms involved, we investigated calcium signalling and gap junctional coupling within and between the RPE and the neural retina in embryonic day (E) 5 chick. We show that the RPE and the ventricular zone (VZ) of the neural retina display spontaneous Ca2+ transients. In the RPE, these often spread as waves between neighbouring cells. In the VZ, the frequency of both Ca2+ transients and waves was lower than in RPE, but increased two‐fold in its presence. Ca2+ signals occasionally crossed the boundary between the RPE and VZ in either direction. In both tissues, the frequency of propagating Ca2+ waves, but not of individual cell transients, was reduced by gap junction blockers. Use of the gap junction permeant tracer Neurobiotin showed that neural retina cells are coupled into clusters that span the thickness of the retina, and that RPE cells are both coupled together and to clusters of cells in the neural retina. Immunolabelling for Cx43 showed this gap junction protein is present at the junction between the RPE and VZ and thus could potentially mediate the coupling of the two tissues. Immunolabelling for β‐tubulin and vimentin showed that clusters of coupled cells in the neural retina comprised mainly progenitor cells. We conclude that gap junctions between progenitor cells, and between these cells and the RPE, may orchestrate retinal proliferation/differentiation, via the propagation of Ca2+ or other signalling molecules.
Induction of neurogenesis in the adult rat subventricular zone and neostriatum following dopamine D3 receptor stimulation
Authors: Van Kampen Jackalina M. , Hagg Theo , Robertson Harold A.
Published: April 2004

Discrete regions of the adult CNS, including the subventricular zone (SVZ), do retain the capacity for neurogenesis. These progenitor cells may represent a potential new source of cells for replacement therapies in neuroregenerative diseases. An understanding of the microenvironmental signals regulating neurogenesis in the adult brain would facilitate the development of such therapeutic approaches. A particularly strong expression of dopamine D3 receptor mRNA occurs in the proliferative SVZ during prenatal and early postnatal ontogeny. Although its expression diminishes following development, a restricted D3 receptor expression persists in this region through adulthood, coincident with continued proliferation in this region. Here, we demonstrate a two‐fold induction of cell proliferation (BrdU incorporation) in the SVZ and rostral migratory stream of the adult Sprague–Dawley rat brain following intrasubventricular administration of the dopamine D3 receptor agonist, 7‐hydroxy‐N,N‐di‐n‐propyl‐2‐aminotetralin (7‐OH‐DPAT) for 2 weeks. The number of BrdU‐positive cells was elevated ten‐fold from very low baseline levels in the neighbouring neostriatum, another region known to express D3 receptors. These striatal BrdU‐positive cells appeared within 3 days following intracerebral infusion of 7‐OH‐DPAT and were distributed homogeneously throughout the striatum following systemic administration. This suggests that these cells originate from resident progenitor cells rather than the SVZ. Dopamine D3 receptor activation may serve as a proneuronal differentiation signal as 60–70% of the new cells had neuronal markers following 7‐OH‐DPAT infusion. These results suggest that the dopamine D3 receptor may be a good drug target for cell replacement strategies, particularly because of the fact that its expression is almost exclusively limited to the nervous system.
Glycine cleavage system in neurogenic regions
Authors: Ichinohe Akiko , Kure Shigeo , Mikawa Sumiko , Ueki Takatoshi , Kojima Kanako , Fujiwara Kazuko , Iinuma Kazuie , Matsubara Yoichi , Sato Kohji
Published: April 2004

The glycine cleavage system (GCS) is the essential enzyme complex for degrading glycine and supplying 5,10‐methylenetetrahydrofolate for DNA synthesis. Inherited deficiency of this system causes nonketotic hyperglycinemia, characterized by severe neurological symptoms and frequent association of brain malformations. Although high levels of glycine have been considered to cause the above‐mentioned problems, the detailed pathogenesis of this disease is still unknown. Here we show that GCS is abundantly expressed in rat embryonic neural stem/progenitor cells in the neuroepithelium, and this expression is transmitted to the radial glia–astrocyte lineage, with prominence in postnatal neurogenic regions. These data indicate that GCS plays important roles in neurogenesis, and suggest that disturbance of neurogenesis induced by deficiency of GCS may be the main pathogenesis of nonketotic hyperglycinemia.
Habenula lesions cause impaired cognitive performance in rats: implications for schizophrenia
Authors: Lecourtier Lucas , Neijt Hans C. , Kelly Peter H.
Published: April 2004

Cognitive impairment is a prominent feature of schizophrenia. Currently there is no well‐accepted explanation of the aetiology of this disorder, but recent evidence indicates that dysfunction of the habenula may be involved. We therefore examined whether habenula lesions in Sprague–Dawley rats cause behavioural changes resembling those of schizophrenia. Rats received either habenula lesions, a sham operation or a small lesion of the overlying dorsal hippocampus as a check that effects observed were not due to incidental damage to this structure. As there are alterations of social behaviour, sensorimotor gating and cognition in schizophrenia, we examined comparable behaviours. Social interaction time was measured during a 5‐min encounter with a novel juvenile conspecific. Prepulse inhibition of an acoustic startle response, as an index of sensorimotor gating, was measured with prepulses of various amplitudes, and spatial cognitive performance was assessed in the Morris water maze task. Histological analysis showed that habenula lesions substantially damaged both medial and lateral habenula bilaterally while largely sparing neighbouring structures. Assay of choline acetyltransferase (ChAT) in the interpeduncular nucleus terminal region of the habenulo‐interpeduncular tract, showed marked reduction (by 80%) in habenula‐lesioned animals. Habenula‐lesioned rats, but not the control group with small dorsal hippocampus lesions, showed marked impairment of Morris maze performance compared to the sham‐operated control group. Social interaction time and prepulse inhibition were not significantly altered in either lesion group. The results are consistent with a role of the habenula in cognition, and with the view that pathology of the habenula may contribute to the cognitive impairments of schizophrenia.
Hippocampal gene expression profiling across eight mouse inbred strains: towards understanding the molecular basis for behaviour
Authors: Fernandes Cathy , Paya‐Cano Jose L. , Sluyter Frans , D'Souza Ursula , Plomin Robert , Schalkwyk Leonard C.
Published: April 2004

Mouse inbred strains differ in many aspects of their phenotypes, and it is known that gene expression does so too. This gives us an opportunity to isolate the genetic aspect of variation in expression and compare it to other phenotypic variables. We have investigated these issues using an eight‐strain expression profile comparison with four replicates per strain on Affymetrix MGU74av2 GeneChips focusing on one well‐defined brain tissue (the hippocampus). We identified substantial strain‐specific variation in hippocampal gene expression, with more than two hundred genes showing strain differences by a very conservative criterion. Many such genetically driven differences in gene expression are likely to result in functional differences including differences in behaviour. A large panel of inbred strains could be used to identify genes functionally involved in particular phenotypes, similar to genetic correlation. The genetic correlation between expression profiles and function is potentially very powerful, especially given the current large‐scale generation of phenotypic data on multiple strains (the Mouse Phenome Project). As an example, the strongest genetic correlation between more than 200 probe sets showing significant differences among our eight inbred strains and a ranking of these strains by aggression phenotype was found forComt, a gene known to be involved in aggression.
Extracellular excitatory amino acids increase in the paraventricular nucleus of male rats during sexual activity: main role of N‐methyl‐d‐aspartic acid receptors in erectile function
Authors: Melis Maria Rosaria , Succu Salvatora , Mascia Maria Stefania , Cortis Luca , Argiolas Antonio
Published: April 2004

The concentrations of glutamic and aspartic acids were measured in the dialysate obtained with vertical microdialysis probes implanted into the paraventricular nucleus of the hypothalamus of sexually potent male rats during sexual activity. Animals showed noncontact erections when put in the presence of, and copulated with, a receptive (ovarietomized oestrogen‐ and progesterone‐primed) female rat. The concentrations of glutamic and aspartic acids in the paraventricular dialysate increased by 37 and 80%, respectively, above baseline values during exposure to the receptive female rat and by 55 and 127%, respectively, during copulation. No changes in the concentrations of glutamic and aspartic acids were detected in the paraventricular dialysate when sexually potent male rats were exposed to nonreceptive (ovariectomized not oestrogen‐ and progesterone‐primed) female rats or when impotent male rats were used. The injection into the paraventricular nucleus of the excitatory amino acid receptor antagonist dizocilpine (5 µg), a noncompetitive N‐methyl‐d‐aspartic acid receptor antagonist, reduced noncontact erections and significantly impaired copulatory activity. The α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid receptor antagonist 6‐cyano‐7‐nitro‐quinoxaline‐2,3‐dione (5 µg) was also able to impair copulatory activity, but to a much lower extent than dizocilpine. In contrast, (±)‐2‐amino‐4‐phosphono‐butanoic acid, a metabotropic receptor antagonist (5 µg), was found to be ineffective. These results confirm the involvement of the paraventricular nucleus in the control of erectile function and copulatory behaviour and show that excitatory amino acid concentration increases in the paraventricular nucleus when penile erection occurs in physiological contexts.
A sensitive model for prediction of relapse in adult acute myeloid leukaemia with t(8;21) using white blood cell count, CD56 and MDR1 gene expression at diagnosis
Authors: Schaich Markus , Koch Rainer , Soucek Silke , Repp Roland , Ehninger Gerhard , Illmer Thomas
Published: April 2004

Acute myeloid leukaemia (AML) carrying t(8;21) has an overall favourable prognosis. However, relapse occurs and the impact of multidrug resistance gene (MDR1) expression on recurring disease in this group of patients is not known. We determined quantifiable MDR1 expression in the bone marrow of 28 AML patients with t(8;21) by a validated real‐time polymerase chain reaction assay. Using MDR1 expression, white blood cell count and CD56 expression at diagnosis we observed complete concordance of predicted and observed relapses. A calculated logit out of these three variables was a strong independent prognostic factor for overall (P = 0·007) and disease‐free survival (P = 0·002).
Comfort on a ward for older people
Authors: Tutton Elizabeth , Seers Kate
Published: April 2004

Background.  Comfort is often considered to be a central part of nursing, although the value placed on it may have diminished over time. Many views of comfort are expressed in the literature but it still remains a diffuse concept that requires further clarification. Research evidence about older people and comfort is limited, and further work is needed to find out how staff and patients view comfort and how it is achieved in practice.

Aims.  This paper reports a study to investigate what comfort means both to older people in hospital and their health care workers.

Research methods.  Ethnography was the methodology chosen, and data were collected using in‐depth interviews with 19 older people and 27 staff members, and 130 hours of participant observation, complemented by additional weekly visits to the study ward.

Findings.  Three themes were identified: the nature of comfort/discomfort; key determinants of comfort/discomfort; and the underlying factors that influence the achievement of comfort/discomfort.

Discussion.  In this hospital setting, the focus of nursing on relief of discomfort suggested a tendency to react to problems, rather than proactively to create an environment that facilitated comfort. Staff were aware of ideals of practice but found these difficult to achieve in reality. In this study comfort was not consistently provided, and some ways of working actively promoted discomfort. As comfort is central to nursing and nursing is central to the care of hospitalized older people, it is crucial that practitioners are enabled to fulfil their potential in this area.
Nurses’ Observation Scale for Inpatient Evaluation: reliability update
Authors: Lyall Dawn , Hawley Chris , Scott Kusam
Published: April 2004

Background.  The Nurses’ Observation Scale for Inpatient Evaluation is a 30‐item scale designed in 1965 for behavioural and observational rating of psychiatric inpatients.

Aim.  This paper reports a re‐evaluation of the Nurses’ Observation Scale for Inpatient Evaluation carried out to confirm that it remains reliable in a modern United Kingdom (UK) setting.

Method.  The scale is a joint‐rated one and we tested the degree of agreement between two individual raters and not, as in previous studies, between two pairs of raters. A total of 100 patients were each rated by two nurses, and a least‐squares simple regression model was used to describe the average level of agreement between the pairs of ratings.

Results.  The correlation in total scale scores was 0·76 (F = 136, P < 0·0001). The correlations for Negative and Positive Factors were 0·68 (P < 0·001) and 0·75 (P < 0·001), respectively.

Conclusion.  This study has shown that the Nurses’ Observation Scale for Inpatient Evaluation retains satisfactory inter‐rater reliability with current clinical populations, and we suggest that it remains a useful tool for everyday clinical practice and a basis for meaningful communication between staff about patient status.
Subtypes of α1‐ and α2‐Adrenoceptors Mediating Noradrenergic Modulation of Spontaneous Inhibitory Postsynaptic Currents in the Hypothalamic Paraventricular Nucleus
Authors: Chong W. , Li L. H. , Lee K. , Lee M. H. , Park J. B. , Ryu P. D.
Published: April 2004

Noradrenergic inputs to the hypothalamic paraventricular nucleus (PVN) play important roles in the regulation of neuroendocrine and autonomic functions. Previous reports show that noradrenaline increases the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in a subpopulation of type II neurones, acting via α1‐adrenoceptors (ARs), but reduces this frequency in most type I and another subpopulation of type II neurones, via α2‐ARs on presynaptic GABA neurones. Here, we identified the subtypes of α‐ARs mediating noradrenaline‐induced increases and decreases in the sIPSC frequency of PVN neurones, by using slice patch recordings from PVN neurones. In both type I and II neurones, the noradrenaline‐induced decrease in sIPSC frequency was completely blocked by BRL44408 (α2A‐AR antagonist) at 1–3 µM, which is approximately 1/100 of its equilibrium dissociation constant (pA2 = 8.0), but not by prazosin (20–100 µM, α2B/C‐AR antagonist; pA2 = 7.5). The effect of noradrenaline was mimicked by guanfacine (α2A‐AR agonist) with an EC50 of 0.1 µM. In type II neurones, the noradrenaline‐induced increase in sIPSC frequency was not blocked by any of the following antagonists: RS17053 (10 µM, α1A‐AR antagonist), BMY7378 (2 µM, α1D‐AR antagonist), prazosin (0.1 µM, α1‐AR antagonist; pA2 = 10.5), or chloroethylclonidine (10 µM, α1B/D‐AR antagonist). However, the effect of noradrenaline was blocked by higher concentrations of prazosin (1 µM) or RS17053 (100 µM), suggesting the involvement of α1L‐subtype, a low affinity form of α1A‐ARs. Collectively, our results indicate that the α2A‐, or α1L‐ARs on the GABA neurones mediate the noradrenaline‐induced decreases, or increases in the frequencies of the sIPSCs of PVN neurones, respectively.
Hepatitis A virus and injecting drug misuse in Aberdeen, Scotland: a case–control study
Authors: Roy K. , Howie H. , Sweeney C. , Parry J. , Molyneaux P. , Goldberg D. , Taylor A.
Published: April 2004

Summary.  To describe an epidemiological investigation of an outbreak of hepatitis A virus (HAV) infection among injecting drug users in Aberdeen, Scotland. A case–control study to determine whether transmission was facilitated by poor personal hygiene or through sharing injecting equipment. Cases were more likely to report not washing their hands after using the toilet [odds ratio (OR) = 12.9, 95% confidence interval (CI) = 1.58–105.89] or before preparing food (OR = 4.0, 95% CI = 1.01–15.8), and less likely to have washed their hands prior to preparing drugs (OR = 10.67, 95% CI = 2.14–53.07). Cases were also more likely to report recipient sharing of needles/syringes (OR = 8.27, 95% CI = 1.68–40.57), and to have had injecting contact with someone who was jaundiced (OR = 29.4, 95% CI = 3.18–271.44). The results indicate that the lack of hygiene within the context of individuals gathering to prepare and inject drugs provides ample opportunity for the transmission of HAV. Although the promotion of good hygiene and the avoidance of sharing injecting equipment are important measures in preventing HAV transmission, they are unlikely to effect major behavioural change. Such measures should, therefore, be reinforced by routinely offering HAV vaccine to injectors.
Epoetin alfa treatment for acute anaemia during interferon plus ribavirin combination therapy for chronic hepatitis C
Authors: Bräu N.
Published: April 2004

Summary.  Infection with the hepatitis C virus (HCV) remains chronic in 75% of infected individuals, in whom it can cause liver inflammation and progressive fibrosis leading to cirrhosis in 20% of patients. A sustained viral response (SVR) to HCV therapy, i.e. undetectable plasma HCV RNA 6 months after the end of treatment, leads to permanent eradication of the virus in 98.3% of patients. The current treatment of choice is combination therapy with pegylated interferon alfa (PEG‐IFN alfa), 2a or 2b, and ribavirin (RBV), which achieves an SVR in 54–56% of patients. In patients with HCV genotype 1, RBV doses of 1000–1200 mg/day are associated with a higher SVR than 800 mg/day (51 vs 40%). However, RBV also causes dose‐dependent reversible haemolytic anaemia that, in combination with the myelosuppressive effects of PEG‐IFN, results in a mean drop in haemoglobin (Hb) level of 3.7 g/dL within 4 weeks. Conventionally, this acute anaemia has been managed with RBV dose reductions. However, this may result in a decreased SVR rate. Alternatively, this anaemia can be managed with administration of epoetin alfa at 40 000 IU once weekly. In a randomized placebo‐controlled trial, treatment with epoetin alfa has been shown to raise Hb levels and maintain RBV doses. Furthermore, the increase in Hb level was associated with improved quality of life. Anaemia in patients treated with interferon plus RBV combination therapy can be managed effectively and safely with once weekly epoetin alfa without sacrificing optimal dosing of RBV.
Restoration of immunity and reactivation of hepatitis B virus after immunosuppressive therapy in a patient with severe aplastic anaemia
Authors: Dai M.‐S. , Kao W.‐Y. , Shyu R.‐Y. , Chao T.‐Y.
Published: April 2004

Summary.  We recently treated a patient with severe aplastic anaemia (SAA) who also had chronic hepatitis B virus (HBV) infection. The HBV serological status at the time of diagnosis of SAA was HBsAg(+) and HBeAg(+). Subsequent analysis of the precore region of HBV DNA showed wild‐type. He received anti‐thymocyte globulin (ATG) and cyclosporin A (CsA) therapy twice. After each course of ATG infusion and during CsA therapy he developed lymphopenia for 1 and 2.5 months, respectively. His serum alanine aminotransferase (ALT) became normalized during the period of lymphopenia, but the serum HBV viral load increased. When his peripheral lymphocytes count recovered, his ALT became elevated again. Lamivudine was effective to normalize his elevated ALT and suppress viral replication. The phenomenon observed in this case supports the prevailing notion that hepatitis B flare‐up in HBV carriers after chemotherapy is caused by an immune‐mediated mechanism. Meanwhile, this is the first documented case of SAA who developed HBV reactivation upon recovery of lymphopenia after immunosuppressive therapy. This also highlights the necessity of pre‐emptive therapy with lamivudine in SAA/HBsAg(+) patients to receive immunosuppressive therapy with ATG/CsA.
Open randomized study of pyrimethamine–sulphadoxine vs. pyrimethamine–sulphadoxine plus probenecid for the treatment of uncomplicated Plasmodium falciparum malaria in children
Authors: Sowunmi A. , Fehintola F. A. , Adedeji A. A. , Gbotosho G. O. , Falade C. O. , Tambo E. , Fateye B. A. , Happi T. C. , Oduola A. M. J.
Published: April 2004

Background  Increasing drug resistance in Plasmodium falciparum has necessitated renewed search for cheap, effective alternatives to commonly available antimalarials, chloroquine and pyrimethamine–sulphadoxine, for the treatment of malaria in Africa. Probenecid, an inhibitor of organic anion transporters and multiresistance‐associated proteins, can chemosensitize P. falciparum to pyrimethamine and sulphadoxine in vitro, but the clinical significance is unclear. We assessed the safety, treatment efficacy, and effects on gametocyte carriage of adding probenecid to pyrimethamine–sulphadoxine.

Methods  We evaluated 151 children aged 12 years or younger who had uncomplicated P. falciparum malaria. Patients were randomly assigned pyrimethamine–sulphadoxine (25 mg/kg of the sulphadoxine component) or pyrimethamine–sulphadoxine as above plus probenecid 20–25 mg/kg of bodyweight in two divided doses daily for 3 days. The primary endpoints were parasitological cure rates on days 14 and 28.

Results  Both regimens were well tolerated; no child was withdrawn because of drug intolerance. Fever (1.9 ± 1.1 vs. 2.4 ± 1.2 days, P = 0.02) and parasite clearance (2.3 ± 0.9 vs. 2.7 ± 1.1 days, P = 0.04) were significantly shorter, and the parasitological cure rate on day 14 (96.2%vs. 83.5%, P = 0.02) but not day 28 (79.4%vs. 72.6%, P = 0.4), was significantly higher in children treated with pyrimethamine–sulphadoxine–probenecid than in those treated with pyrimethamine–sulphadoxine. Gametocyte carriage was similar with both treatment regimens.

Conclusions  The combination of pyrimethamine–sulphadoxine, and probenecid, at a relatively moderate dose, improved treatment efficacy but had no effect on gametocyte carriage. The pyrimethamine–sulphadoxine–probenecid combination merits further evaluation as a potential treatment for use in Nigeria.