bluuebunny/crossref_metadata_2025 huggingface dataset:
Formative evaluation to benchmark and improve climate-based decision support for graziers in Western Queensland
Authors: Keogh D. U. , Bell K. L. , Park J. N. , Cobon D. H.
Published: April 2004

Researchers developing climate-based forecasts, workshops, software tools and information to aid grazier decisions undertook an evaluation study to enhance planning and benchmark impact. One hundred graziers in Western Queensland were randomly selected from 7 shires and surveyed by mail and telephone (43 respondents) to explore levels of knowledge and use of climate information, practices and information needs. We found 36% of respondents apply the Southern Oscillation Index to property decisions but 92% were unaware El Niño Southern Oscillation's predictive signal in the region is greater for pasture growth than rainfall, suggesting they may not recognise the potential of pasture growth forecasts. Almost 75% of graziers consider they are conservative or risk averse in their attitude to managing their enterprise. Mail respondents (n = 20) if given a 68%, on average, probability of exceeding median rainfall forecast may change a decision; almost two-thirds vary stocking rate based on forage available, last year's pasture growth or the Southern Oscillation Index; the balance maintain a constant stocking rate strategy; 90% have access to a computer; 75% to the internet and 95% have a fax. This paper presents findings of the study and draws comparisons with a similar study of 174 irrigators in the Northern Murray–Darling Basin (Aust. J. Exp. Ag. 44, 247–257). New insights and information gained are helping the team better understand client needs and plan, design and extend tools and information tailored to grazier knowledge, practice, information needs and preferences. Results have also provided a benchmark against which to measure project impact and have influenced the team to make important changes to their project planning, activities and methods for transferring technology tailored to grazier preferences.
Surface soil water dynamics in pastures in northern New South Wales. 2. Surface runoff
Authors: Murphy S. R. , Lodge G. M. , Harden S.
Published: April 2004

Surface runoff can represent a significant part of the hydrological balance of grazed pastures on the north-west slopes of New South Wales, and is influenced by a range of rainfall characteristic, soil property, and pasture conditions. Runoff plots were established on grazed pastures at 3 sites as part of the Sustainable Grazing Systems National Experiment (SGS NE). Pastures were either native (redgrass, wallaby grass and wire grass) or sown species (phalaris, subterranean clover and lucerne) and a range of grazing management treatments were imposed to manipulate pasture herbage mass, litter mass and ground cover. Rainfall and runoff events were recorded using automatic data loggers between January 1998 and September 2001. Stored soil water in the surface layer (0–22.5 cm) was monitored continuously using electrical resistance sensors and automatic loggers. Pasture herbage mass, litter mass and ground cover were estimated regularly to provide information useful in interpreting runoff generation processes.Total runoff ranged from 6.6 mm at Manilla (0.3% of rainfall) to 185 mm at Nundle (5.7% of rainfall) for different grazing treatments, with the largest runoff event being recorded at Nundle (46.7 mm). Combined site linear regression analyses showed that soil depth, rainfall depth and rainfall duration explained up to 30.3% of the variation in runoff depth. For individual sites, these same variables were also important, accounting for 13.3–33.6% of the variation in runoff depth. Continuous monitoring of stored soil water in relation to these runoff events indicated that the majority of these events were generated by saturation excess, with major events in winter contributing substantially to regional flooding. Long-term simulation modelling (1957–2001) using the SGS Pasture Model indicated that most runoff events were generated in summer, which concurred with the number of flood events recorded at Gunnedah, NSW, downstream of the SGS sites. However, floods also occurred frequently in winter, but the simulations generated few runoff events at that time of the year. These results have important implications for sustainability of grazed pastures and long-term simulation modelling of the hydrological balance of such systems, since runoff generation processes are likely to vary both spatially and temporally for different rainfall events.
Morphological Decomposition and the Reverse Base Frequency Effect
Authors: Taft Marcus
Published: April 2004

If recognition of a polymorphemic word always takes place via its decomposition into stem and affix, then the higher the frequency of its stem (i.e., base frequency) the easier the lexical decision response should be when frequency of the word itself (i.e., surface frequency) is controlled. Past experiments have demonstrated such a base frequency effect, but not under all circumstances. Thus, a dual pathway notion has become dominant as an account of morphological processing whereby both decomposition and whole–word access is possible. Two experiments are reported here that demonstrate how an obligatory decomposition account can handle the absence of base frequency effects. In particular, it is shown that the later stage of recombining the stem and affix is harder for high base frequency words than for lower base frequency words when matched on surface frequency, and that this can counterbalance the advantage of easier access to the higher frequency stem. When the combination stage is crucial for discriminating the word items from the nonword items, a reverse base frequency effect emerges, revealing the disadvantage at this stage for high base frequency words. Such an effect is hard for the dual–pathway account to explain, but follows naturally from the idea of obligatory decomposition.
“The Labor-Less Labor Supply Model” in the Era Before Philip Wicksteed
Authors: Spencer David A.
Published: April 2004

In a recent article in this journal, Laurent Derobert (2001) examined the origins of the canonical model of labor supply. According to this model, workers will exchange “leisure” for work at a rate determined by the hourly wage. In this case, labor supply will be a simple function of the utility of leisure and the utility of income. Paradoxically, this permits the understanding of labor supply to proceed without consideration of labor itself. Derobert identifies Philip H. Wicksteed (1910) as the originator of this approach. Apparently he was the first economist to model labor supply in terms of a leisure-income trade-off. Thus it is claimed that Wicksteed bequeathed to the economics profession the paradox of the “labor-less labor supply model.”
The Proinsulin C‐peptide—A Multirole Model
Authors: Steiner Donald F.
Published: April 2004

The C‐peptide links the insulin A and B chains in proinsulin,
providing thereby a means to promote their efficient
folding and assembly in the endoplasmic reticulum during
insulin biosynthesis. It then facilitates the intracellular
transport, sorting, and proteolytic processing of proinsulin
into biologically active insulin in the maturing secretory
granules of the β cells. These manifold functions impose significant
constraints on the C‐peptide structure that are conserved
in evolution. After cleavage of proinsulin, the intact
C‐peptide is stored with insulin in the soluble phase of the
secretory granules and is subsequently released in equimolar
amounts with insulin, providing a useful independent
indicator of insulin secretion. This brief review highlights
many aspects of its roles in biosynthesis, as a prelude to
consideration of its possible additional role(s) as a physiologically
active peptide after its release with insulin into the
circulation in vivo.
Molecular and Cellular Effects of C‐peptide—New Perspectives on an Old Peptide
Authors: Wahren John , Shafqat Jawed , Johansson Jan , Chibalin Alexander , Ekberg Karin , Jörnvall Hans
Published: April 2004

New results present C‐peptide as a biologically active
peptide hormone in its own right. Although C‐peptide is
formed from proinsulin and cosecreted with insulin, it is a
separate entity with biochemical and physiological characteristics
that differ from those of insulin. There is direct
evidence of stereospecific binding of C‐peptide to a
cell surface receptor, which is different from those for insulin
and other related hormones. The C‐peptide binding
site is most likely a G–protein–coupled receptor. The association
constant for C‐peptide binding is approximately
3 × 109M-1. Saturation of the binding occurs already at a
concentration of about 1 nM, which explains why C‐peptide
effects are not observed in healthy subjects. Binding of C‐peptide
results in activation of Ca2+ and MAPK‐dependent
pathways and stimulation of Na+,K+‐ATPase and eNOS
activities. The latter 2 enzymes are both deficient in several
tissues in type 1 diabetes. There is some evidence that
C‐peptide, and insulin may interact synergistically on the
insulin signaling pathway. Clinical evidence suggests that
replacement of C‐peptide, together with regular insulin
therapy, may be beneficial in patients with type 1 diabetes
and serve to retard or prevent the development of long‐term
complications.
Educational Inequality and the Expansion of UK Higher Education
Authors: Blanden Jo , Machin Stephen
Published: April 2004

In this paper we explore changes over time in higher education (HE) participation and attainment between people from richer and poorer family backgrounds during a time period when the UK higher education system expanded at a rapid rate. We use longitudinal data from three time periods to study temporal shifts in HE participation and attainment across parental income groups for children going to university in the 1970s, 1980s and 1990s. The key finding is a highly policy relevant one, namely that HE expansion has not been equally distributed across people from richer and poorer backgrounds. Rather, it has disproportionately benefited children from relatively rich families. Despite the fact that many more children from higher income backgrounds participated in HE before the recent expansion of the system, the expansion acted to widen participation gaps between rich and poor children. This finding is robust to different measures of education participation and inequality. It also emerges from non‐parametric estimations and from a more detailed econometric model allowing for the sequential nature of education choices with potentially different income associations at different stages of the education sequence.
Unemployment Benefits, Contract Length and Nominal Wage Flexibility
Authors: Calmfors Lars , Johansson Åsa
Published: April 2004

In a bargaining model, we show that a decrease in the unemployment benefit level increases not only equilibrium employment, but also nominal wage flexibility, and thus reduces employment variations in the case of nominal shocks. Long‐term wage contracts lead to higher expected real wages and hence higher expected unemployment than short‐term contracts. Therefore, a decrease in the benefit level reduces the expected utility gross of contract costs of a union member more with long‐term than with short‐term contracts, thereby creating an incentive for shorter contracts. Incentives for employers are shown to change in the same direction.
Energy failure in astrocytes increases the vulnerability of neurons to spreading depression
Authors: Lian Xiao‐Yuan , Stringer Janet L.
Published: April 2004

A neuroprotective role of astrocytes has been hypothesized, but the mechanism is debated and in vivo evidence is limited. To test this hypothesis, a sublethal stressor (spreading depression) and fluorocitrate (FC), a selective inhibitor of the astrocytic Krebs cycle, were used in urethane‐anaesthetized adult rats. Neuronal damage was assessed 24 h after treatment with silver stain and immunoreactivity for a 72‐kDa heat‐shock protein. ATP levels and mitochondrial aconitase activity, a marker indicating exposure to reactive oxygen species, were measured after 4 and 24 h. Spreading depression alone did not affect ATP levels, mitochondrial aconitase activity, or induce neuronal injury in the cortex. Local or intraventricular injection of FC significantly decreased ATP levels and mitochondrial aconitase activity, but did not produce neuronal damage. In animals receiving injections of FC and then spreading depression, there was evidence of significant neuronal stress and damage. Isocitrate, which bypasses the metabolic inhibition produced by FC, prevented all of the changes seen after the combination of FC and spreading depression. One‐hour pretreatment with dimethyl sulfoxide (a scavenger of hydroxyl radicals), deferoxamine (an iron chelator) or fructose‐1,6‐bisphosphate also blocked inactivation of mitochondrial aconitase, ATP depletion and the neuronal damage induced by FC and spreading depression. These experiments demonstrate that inhibition of the metabolism of astrocytes, with a decrease in ATP levels, will increase the susceptibility of neurons to the stress induced by spreading depression. The neuroprotective effects of dimethyl sulfoxide, deferoxamine and fructose‐1,6‐bisphosphate suggest that oxidative stress contributes to the neurotoxicity in this situation.
Stage‐specific and opposing roles of BDNF, NT‐3 and bFGF in differentiation of purified callosal projection neurons toward cellular repair of complex circuitry
Authors: Catapano Lisa A. , Arlotta Paola , Cage Tene A. , Macklis Jeffrey D.
Published: April 2004

Cellular repair of neuronal circuitry affected by neurodegenerative disease or injury may be approached in the adult neocortex via transplantation of neural precursors (“neural stem cells”) or via molecular manipulation and recruitment of new neurons from endogenous precursors in situ. A major challenge for potential future approaches to neuronal replacement will be to specifically direct and control progressive differentiation, axonal projection and connectivity of neural precursors along a specific neuronal lineage. This goal will require a progressively more detailed understanding of the molecular controls over morphologic differentiation of specific neuronal lineages, including neurite outgrowth and elongation, in order to accurately permit and direct proper neuronal integration and connectivity. Here, we investigate controls over the morphologic differentiation of a specific prototypical lineage of cortical neurons: callosal projection neurons (CPN). We highly enriched CPN to an essentially pure population, and cultured them at three distinct stages of development from embryonic and postnatal mouse cortex by retrograde fluorescence labelling, followed by fluorescence‐activated cell sorting. We find that specific peptide growth factors exert direct stage‐specific positive and negative effects over the morphologic differentiation and process outgrowth of CPN. These effects are distinct from the effects of these growth factors on CPN survival [Catapano et al. (2001)J. Neurosci., 21, 8863–8872]. These data may be critical for the future goal of directing lineage‐specific neuronal differentiation of transplanted or endogenous precursors/“stem cells” toward cellular repair of complex cortical circuitry.
Subunit‐specific P2X‐receptor expression defines chemosensory properties of trigeminal neurons
Authors: Spehr Jennifer , Spehr Marc , Hatt Hanns , Wetzel Christian H.
Published: April 2004

The facial innervation pattern of trigeminal nerve fibres comprises the innervation of the nasal epithelium, where free trigeminal nerve endings contribute to detection and discrimination of chemical stimuli including odourants. The signal transduction mechanisms in sensory nerve endings underlying perception of chemical stimuli remain widely uncovered. Here, we characterized trigeminal ATP‐activated P2X receptors in cultured rat trigeminal neurons and investigated their role in chemoperception. We identified a new subpopulation of neurons lacking typical nociceptive characteristics and expressing homomeric P2X2 receptors. Using a certain group of chemicals known as trigeminal stimuli we found no direct activation of trigeminal neurons, but a modulation of P2X2 receptor mediated currents. In contrast, P2X3 receptor mediated currents of nociceptive trigeminal neurons remained unaffected by the tested chemicals. Therefore, we assume a functional role for the newly identified subpopulation in chemodetection of certain trigeminal stimuli.
Nigral GABAergic inhibition upon mesencephalic dopaminergic cell groups in rats
Authors: Saitoh Kazuya , Isa Tadashi , Takakusaki Kaoru
Published: April 2004

Synaptic inhibition from the substantia nigra pars reticulata (SNr) to the mesencephalic dopaminergic neurons, which was mediated by gamma (γ)‐amino‐butyric acid (GABA), was investigated in a midbrain slice preparation of Wistar rats. Whole‐cell patch‐clamp recordings were used to record synaptic potentials/currents from the dopaminergic neurons (n = 93) located in the retrorubral field (n = 22), the substantia nigra pars compacta (n = 47) and the ventral tegmental area (n = 24). In the presence of ionotropic glutamate receptor antagonists electrical stimulation of the SNr induced inhibitory postsynaptic potentials (IPSPs) and/or currents (IPSCs) in 83 neurons. The IPSPs/IPSCs were comprised early and late components. The early IPSPs/IPSCs were mediated by chloride currents through GABAA receptors. The late IPSPs/IPSCs were mediated by potassium currents through GABAB receptors. Both GABAA‐ and GABAB‐IPSPs were amplified by repetitive stimuli with frequencies between 25 and 200 Hz. This frequency range covers the firing frequencies of SNr neurons in vivo. It was observed that an application of a GABAB receptor antagonist increased the amplitude of the GABAA‐IPSPs. The amplification was followed by a rebound depolarization that induced transient firing of dopaminergic neurons. These properties of the IPSPs were common in all of the three dopaminergic nuclei. These results suggest that postsynaptic GABAA‐ and GABAB‐inhibition contribute to transient and persistent alternations of the excitability of dopaminergic neurons, respectively. These postsynaptic mechanisms may be, in turn, regulated by presynaptic GABAB‐inhibition. Nigral GABAergic input may provide the temporospatial regulation of the background excitability of mesencephalic dopaminergic systems.
Functional maturation of isolated neural progenitor cells from the adult rat hippocampus
Authors: Hogg Ron C. , Chipperfield Hiram , Whyte Kathryn A. , Stafford Mark R. , Hansen Mitchell A. , Cool Simon M. , Nurcombe Victor , Adams David J.
Published: April 2004

Although neural progenitor cells (NPCs) may provide a source of new neurons to alleviate neural trauma, little is known about their electrical properties as they differentiate. We have previously shown that single NPCs from the adult rat hippocampus can be cloned in the presence of heparan sulphate chains purified from the hippocampus, and that these cells can be pushed into a proliferative phenotype with the mitogen FGF2 [Chipperfield, H., Bedi, K.S., Cool, S.M. & Nurcombe, V. (2002) Int. J. Dev. Biol., 46, 661–670]. In this study, the active and passive electrical properties of both undifferentiated and differentiated adult hippocampal NPCs, from 0 to 12 days in vitro as single‐cell preparations, were investigated. Sparsely plated, undifferentiated NPCs had a resting membrane potential of ≈ −90 mV and were electrically inexcitable. In > 70%, ATP and benzoylbenzoyl‐ATP evoked an inward current and membrane depolarization, whereas acetylcholine, noradrenaline, glutamate and GABA had no detectable effect. In Fura‐2‐loaded undifferentiated NPCs, ATP and benzoylbenzoyl‐ATP evoked a transient increase in the intracellular free Ca2+ concentration, which was dependent on extracellular Ca2+ and was inhibited reversibly by pyridoxalphosphate‐6‐azophenyl‐2′‐4′‐disulphonic acid (PPADS), a P2 receptor antagonist. After differentiation, NPC‐derived neurons became electrically excitable, expressing voltage‐dependent TTX‐sensitive Na+ channels, low‐ and high‐voltage‐activated Ca2+ channels and delayed‐rectifier K+ channels. Differentiated cells also possessed functional glutamate, GABA, glycine and purinergic (P2X) receptors. Appearance of voltage‐dependent and ligand‐gated ion channels appears to be an important early step in the differentiation of NPCs.
‘Hearing’ syllables by ‘seeing’ visual stimuli
Authors: Jäncke Lutz , Shah Nadim Joni
Published: April 2004

Currently it is discussed whether the same cortical areas are activated during the imagination of as during the actual presentation of specific stimuli. Some argue that mostly the secondary but not the primary sensory areas are active during imagination. Using functional magnetic resonance imaging we explored whether auditory verbal imagery of syllables has sufficient power to evoke haemodynamic responses in the auditory cortex. To overcome the detrimental effects of scanner noise, one group of subjects was trained to vividly imagine hearing a syllable while a flashlight was presented. A control group did not receive this training. We found that only the trained group revealed haemodynamic responses in the auditory cortex during auditory imagination while the control group showed no activation within the auditory cortex. Peak activations during auditory verbal imagery are located bilaterally within the superior temporal gyrus region in the vicinity of the planum temporale. While these secondary auditory areas are active during auditory verbal imagery, there was no activation in Heschl's gyrus. We hypothesize that auditory verbal imagery is associated with haemodynamic responses in secondary auditory and not primary auditory areas.
Sex differences in adult suprachiasmatic nucleus neurons emerging late prenatally in rats
Authors: Abizaid Alfonso , Mezei Gabor , Sotonyi Peter , Horvath Tamas L.
Published: April 2004

The suprachiasmatic nucleus (SCN) is implicated in the control of circadian rhythms of gonadal function. Although several structures surrounding the SCN are sensitive to the effects of gonadal steroids, similar effects in the SCN remain unclear. For example, there are conflicting data on whether the SCN is sexually differentiated. This study attempted to determine sex differences in the number of SCN cells generated during late gestation, and if testosterone mediates these differences. Pregnant female rats were treated with 5‐bromo‐2′‐deoxyuridine (BrdU; 50 mg/kg) on gestational day 18 (E18), the day when aromatase activity peaks in the developing rat fetus. These animals were also given injections of oil or testosterone propionate (10 mg/0.1 mL peanut oil) from E15 until parturition. Litters were allowed to survive until adulthood and were killed on postnatal day 60 (PN60). Following fixation, brain sections containing the SCN from these rats were processed for BrdU immunocytochemistry. A second set of SCN sections was processed for immunocytochemistry detecting BrdU and some of the cell groups prevalent within the SCN. Data showed that female rats have a higher number of cells labeled with BrdU in the SCN, particularly in the medial and caudal SCN. This sex difference was abolished in animals treated with testosterone during late gestation. Double immunocytochemistry revealed that BrdU‐labeled cells were neurons expressing calbindin‐D28K, vasoactive intestinal peptide and, to a lesser degree, vasopressin. Our results unveiled a previously unknown effect of gonadal steroids on the developing SCN, which may contribute to the emergence of gender‐specific circadian rhythms.
Hydrogen peroxide in the Burkitt's lymphoma cell line Raji provides protection against arsenic trioxide‐induced apoptosis via the phosphoinositide‐3 kinase signalling pathway
Authors: Lu Di , Bai Xiao‐Chun , Gui Li , Su Yong‐Chun , Deng Fan , Liu Bin , Li Xiu‐Mei , Zeng Wei‐Sen , Cheng Bao‐Luan , Luo Shen‐Qiu
Published: April 2004

Many anticarcinogenic drugs kill tumour cells by inducing apoptosis. We examined the effects of hydrogen peroxide (H2O2) on arsenic trioxide (As2O3)‐induced cell killing. Low concentrations of H2O2 (200 μmol/l) inhibited the ability of As2O3 to induce apoptosis in the Burkitt's lymphoma cell line Raji. H2O2 altered the form of cell death from apoptosis to pyknosis/necrosis and also lowered the degree of cell killing by As2O3. H2O2 was capable of preventing caspase‐3 activation induced by As2O3 in Raji cells. Incubation of cells with a phosphoinositide‐3 kinase (PI‐3K) inhibitor, wortmannin (100 nmol/l), blocked the effects of H2O2 on As2O3‐induced caspase‐3 activation. In addition, the PI‐3K inhibitor partially blocked the effects of H2O2 on up‐regulation of Bcl‐2 and Bcl‐XL protein expression, down‐regulation of Bax protein expression, and phosphorylation of Bcl‐2 and IκBα. This investigation demonstrated for the first time that low concentrations of H2O2 provide protection against the in vivo of As2O3‐induced apoptosis. PI‐3K plays a crucial role in enhancing cell survival during H2O2, inhibiting As2O3‐induced apoptosis in the Burkitt's lymphoma cells. As2O3‐induced cancer cell apoptosis may be enhanced by certain antioxidants in the treatment protocol.
Comparative analysis of clinical outcomes after allogeneic bone marrow transplantationversusperipheral blood stem cell transplantation from a related donor in Japanese patients
Authors: Tanimoto Tetsuya E. , Yamaguchi Takuhiro , Tanaka Yuji , Saito Akiko , Tajima Kinuko , Karasuno Takahiro , Kasai Masanobu , Kishi Kenji , Mori Takehiko , Maseki Nobuo , Morishima Satoko , Miyakoshi Shigesaburo , Kasai Masaharu , Ohno Yuju , Kim Sung‐Won , Numata Akihiko , Kami Masahiro , Takaue Yoichi , Mori Shin‐ichiro , Harada Mine
Published: April 2004

A reduced incidence of graftversushost disease (GvHD) has been documented among Japanese allogeneic bone marrow transplantation (BMT) patients, as the Japanese are genetically more homogeneous than western populations. To clarify whether this ethnic difference affects the results of allogeneic peripheral blood stem cell transplantation (PBSCT), we conducted a nationwide survey to compare clinical outcomes of allogeneic PBSCT (n = 214) and BMT (n = 295) from a human leucocyte antigen‐identical‐related donor in Japanese patients. The cumulative incidence of grades II–IV acute GvHD was 37·4% for PBSCT and 32·0% for BMT. The cumulative incidence of extensive chronic GvHD at 1 year was significantly higher after PBSCT than BMT (42% vs. 27%;P < 0·01). The organ involvement patterns of GvHD were different between the two groups. By multivariate analyses, the incidence of chronic GvHD was significantly increased in PBSCT, whereas the stem cell source did not affect the incidence of acute GvHD, transplant‐related mortality, relapse or survival. We concluded that Japanese PBSCT patients have an increased risk of chronic GvHD compared with BMT patients, but the incidence of acute GvHD was still lower than in western populations. Thus, the choice of haematopoietic stem cell source should be considered based on data for individual ethnic populations.
Cancer symptom transition periods of children and families
Authors: Woodgate Roberta Lynn , Degner Lesley Faith
Published: April 2004

Background.  Children with cancer are reported to experience many symptoms during the cancer trajectory. However, minimal qualitative research has been conducted that explores children's and families’ experiences of symptoms. An understanding of the symptom trajectory, grounded in children's and families’ experiences, is essential to providing comprehensive and sensitive care to children with cancer and their families.

Aim.  This paper reports a study designed to explore and describe the symptom course in childhood cancer as experienced by children and their families.

Design.  Guided by the philosophy of interpretive interactionism, a longitudinal qualitative study was undertaken. A purposive sample of 39 families of children with cancer who resided in Western Canada participated. The children ranged in age from 4·5 to 18 years and varied in their cancer diagnoses.

Methods.  Multiple data collection methods included formal and informal interviewing and participant observation. Data were analysed by the constant comparative method. Development of illness narratives added to an understanding of children's and families’ experiences.

Findings.  A substantive theory entitled ‘Children's and Families’ Lived Experience of Childhood Cancer Symptoms’ emerged from the findings. This depicts the experience of cancer in relation to children's changing symptom trajectory. A core category of the theory, ‘passage through the transition periods’, shows how changing symptom experiences affected children's and families’ ways of being in the world. These were reflected in six transition periods: (1) it is just the flu; (2) it is more than the flu; (3) it hits home; (4) it is nasty; (5) it is not so bad, it is pretty good; and (6) it is ‘dragsville’. The changing roles and responsibilities of family members, and how the family existed in the cancer world, varied depending on the transition period through which they were passing.

Conclusions.  Transition periods not only reinforce the dynamic nature of the experience of childhood cancer but, more importantly, show how symptoms can greatly affect the quality of children's and families’ day‐to‐day living. Interpreting cancer in the context of the symptom trajectory provides nurses with a new perspective for understanding childhood cancer, and will assist in the development of symptom relief strategies that will help to contain symptoms and improve overall quality of life for children and families.
The ethics of non‐intervention in a study of patients awaiting coronary artery bypass surgery
Authors: Fitzsimons Donna , McAloon Toni
Published: April 2004

Background.  Nurses conducting clinical research frequently encounter ethically challenging situations that require careful analysis if the decisions taken are to be in the best interests of participants, researchers and society. There is a lack of literature which discusses the ethical aspects of the nurse's role in clinical research studies.

Aim.  The aim of this paper is to discuss the ethical conflicts and decisions taken during a combined qualitative and quantitative study of patients’ experiences whilst awaiting coronary bypass surgery.

Discussion.  Ethical conflict arose because, despite having gained ethics approval for a non‐interventional study, the researcher became concerned for the health of some research participants, whose condition was observed to have deteriorated. During the course of the study four of the 70 participants died. As a result, changes to the original research protocol were negotiated and subsequently the researcher intervened in cases where participants’ clinical condition had worsened.

Conclusion.  Nurses conducting clinical research studies can face serious ethical dilemmas, particularly if participants’ health is at risk. This paper demonstrates the potential for both role conflict and role convergence in nursing research. We contend that since the roles of researcher and clinician are not mutually exclusive, the interface between the two requires further discussion. The paper may to help inform other researchers who struggle with the issue of non‐intervention when presented with research participants in need of professional nursing care.
Changes of Atrial Natriuretic Peptide in Rat Supraoptic Neurones During Pregnancy
Authors: Jankowski M. , Marcinkiewicz M. , Bouanga J.‐C. , Gutkowska J.
Published: April 2004

To better understand the role of atrial natriuretic peptide (ANP) in the central regulation of hydro‐mineral homeostasis, we analysed its expression in rat hypothalamic neurones during gestation and postpartum. These physiological events are characterized by opposing body fluid regulations. Quantitative in situ hybridization analysis showed that starting from mid‐pregnancy, ANP mRNA declined in neurones of the preoptic area, periventricular area, lateral hypothalamus and endorhinal nucleus, and remained low at postpartum. By contrast, magnocellular cells in the supraoptic nucleus (SON) showed four‐ and 10‐fold more ANP mRNA in sections from preterm and postpartum rats, respectively, compared to nonpregnant controls (P < 0.001). Oxytocin mRNA paralleled ANP mRNA expression in the SON, whereas vasopressin mRNA rose in early pregnancy and declined thereafter. High hypothalamic ANP concentration at day 21 of gestation versus nonpregnant rats (3.1 ± 0.5 versus 1.8 ± 0.4 ng/mg protein, P < 0.05) suggested that ANP transcript accumulation in the SON is associated with increased utilization of the peptide. The elevation of hypothalamic ANP (two‐fold) and ANP receptors by treatment of ovariectomized rats with 17β‐oestradiol (25 µg/rat, 10 days) was abolished by coadministration of progesterone. Thus, we concluded that elevated oestradiol at term stimulates ANP synthesis and paracrine ANP activation in the hypothalamus. Overall, we provide experimental, anatomical and molecular evidence for ANP regulation in hypothalamic neurones at preterm and after 17β‐oestradiol stimulation. Our study supports the concept that ANP expressed in the SON acts as a peptidergic neurotransmitter involved in water and salt regulation during pregnancy and postpartum.
Does an ‘autoimmune’ profile affect the clinical profile of chronic hepatitis C? An Italian multicentre survey
Authors: Stroffolini T. , Colloredo G. , Gaeta G. B. , Sonzogni A. , Angeletti S. , Marignani M. , Pasquale G. , Venezia G. , Craxì A. , Almasio P.
Published: April 2004

Summary.  Nonorgan‐specific autoantibodies (NOSA) are common in patients with chronic hepatitis C virus infection. It is unclear whether serological markers of autoimmunity segregate in a cohort of cases with more severe liver damage. We assessed the relationship between NOSA and demographic, biochemical and histological features in 502 subjects with anti‐HCV positive, HCV‐RNA positive, HBsAg negative chronic hepatitis consecutively referred to four Italian liver units. Percutaneous liver biopsy was performed in all subjects. A single pathologist scored the biopsies using histology activity index classification. The overall prevalence of positivity for any NOSA was 36.9%. Antinuclear antibodies, anti‐smooth muscle antibodies, and anti‐liver/kidney microsomal antibodies were found in 15.7, 27.3 and 2.2% of cases. Multivariate analysis showed that γ‐globulin >2 g/dL was the only independent predictor of the likelihood of NOSA positivity (OR, 2.1; 95% CI, 1.3–3.4). No other clinical (age, gender, ALT, HCV genotype) or histological features (grading and staging score, bile ductular damage) were linked to NOSA. Antiviral therapy in 155 subjects with NOSA did not cause any adverse events related to autoimmunity during and after treatment. The presence of NOSA in patients with chronic HCV hepatitis is not related to specific demographic features and has no impact on the biochemical and histological profile of the liver disease at presentation and the response to antiviral treatment.
Cutis laxa‐like pseudoxanthoma elasticum with ossification
Authors: Bahadir Sevgi , Çobanoğlu Ümit , Şiviloḡlu Çiğdem , Kapicioḡlu Zerrin , Baykan Merih
Published: April 2004

Pseudoxanthoma elasticum (PXE) is a heritable disorder of elastic fibers characterized by yellowish, coalescing papules on the flexural area, which is loose and wrinkled. A 35‐year‐old woman presented cutis laxa‐like marked wrinkling and yellowish papules, and a skin biopsy revealed ossification and fragmentation of elastic fibers in the dermis. Ophthalmologic examination revealed a peau d’orange appearance of the retina. She was also found to have a mitral stenosis and hypertension. This is an unusual case of concurrent ossification and cutis laxa‐like PXE.
Annular lichen planus involving the esophagus: a rare diagnosis
Authors: Belloul Lamia , Akhdari Nadia , Hassar Imane , Lakhdar Hakima
Published: April 2004

A 49‐year‐old woman presented with a 2‐year history of a sore mouth, annular, atrophic patches, and chronic ulcerative vulvovaginitis. For 6 years, she had suffered from dysphagia to solids which was increasing in severity. There was no past history of heartburn or other symptoms of esophageal reflux.

Mucocutaneous examination showed white erosive patches on the buccal mucosa, cicatricial alopecia, dystrophic nails, and annular atrophic pigmented plaques localized on the trunk (Fig. 1). Genital examination showed atrophic and sclerotic vulvovaginal lesions with synechia. Cutaneous biopsy showed an atrophic epidermis, a dense lymphocytic infiltrate in the upper dermis with degeneration of the basal epithelium, and Civatte bodies. Serologic tests for hepatitis B and C were negative. A diagnosis of cutaneous annular lichen planus with nail, scalp, oral, and genital involvement was made.

Annular, atrophic, and pigmented plaques localized on the back

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Fiberoptic endoscopy, undertaken 6 years previously, revealed erosive and two ulcerative lesions in the esophagus, extending to 20 cm from the incisors. Biopsy from the affected upper esophagus revealed nonspecific inflammatory changes with lymphocytic infiltration. A barium swallow revealed a 5‐mm, regular and inflammatory stricture in the upper esophagus (Fig. 2). A diagnosis of stenosing lichen planus of the esophagus was made 6 years after the first symptoms of dysphagia. Treatment was started with oral prednisolone, 50 mg daily.

Barium swallow: regular and inflammatory stricture in the upper esophagus

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The role of psychological factors in alopecia areata and the impact of the disease on the quality of life
Authors: Güleç A. Tülin , Tanrıverdi Nilgün , Dürü Çağay , Saray Yasemin , Akçalı Cenk
Published: April 2004

Background  The role of psychological factors in the pathogenesis of alopecia areata (AA) has long been the subject of debate. Numerous studies have provided controversial results.

Aim  This case–control study was undertaken to determine the significance of stressful life events and other psychological factors in the etiopathogenesis of AA. The impact of the disease on the quality of life was also assessed.

Methods  Fifty‐two adult patients (18 females and 34 males) diagnosed with AA and 52 age‐ and sex‐matched individuals selected from hospital staff without any hair loss (control group) were evaluated using the major life events scale, Beck depression and Beck anxiety inventories, and the Short Form‐36 health survey (SF‐36). In addition, comparison was performed between two patient groups created according to whether or not they linked emotional trauma with their AA attack.

Results  There was no statistically significant difference between the patient and control groups with regard to the total scores of stressful major life events, depression, and anxiety. Of the eight subscales on SF‐36, vitality and mental health scores were higher in the control group, whereas social functioning scores were higher in the patients. The total number of stressful life events was higher in patients who attributed their disease to a stressful life event than in those who did not.

Conclusions  It appears unlikely that anxiety and depression play a major role in the etiopathogenesis of AA, but stressful life events may act as a trigger in the onset and/or exacerbation of the disease. Furthermore, AA seems to have a partly negative impact on the health‐related quality of life.
How is patient‐centred care understood by the clinical, managerial and lay stakeholders responsible for promoting this agenda?
Authors: Gillespie Rosemary , Florin Dominique , Gillam Steve
Published: April 2004

Aims and objectives This study explores how the term patient‐centred care is understood, particularly by those who are involved in translating the concept from a theoretical idea into a practical application. It examines the ways in which intermediate level stakeholders such as health service managers, educationalists, professional leaders and officers of patient bodies understand and promote patient‐centred care among health professionals actually delivering patient care.

Design Qualitative interview study.

Setting and participants Interviewees were drawn from groups and organizations from four categories: health agencies and regulatory bodies, Royal Colleges and other professional bodies, educational institutions, patient and user groups and consumer organizations.

Main variables studied The meanings and understandings of patient‐centred care, commitment to implementing patient‐centred care and barriers and opportunities to implementation.

Results and conclusions Patient‐centred care covers a range of activities from patient involvement in individual care to public involvement in health policy decisions. Current Department of Health policy has made patient‐centred care a priority, but has not clarified exactly what it means. Thus, health professionals, educationalists, managers and patient representatives have all developed different meanings of patient‐centred care to reflect their own particular backgrounds and roles. The individual aspects of patient‐centred care have been neglected in policy terms and important research findings have not been incorporated into policies to change the attitudes and behaviours of health professionals. Developing a shared understanding of patient‐centred care which encompasses all its components is an important role for the new Commission for Patient and Public Involvement.
Consulted but not heard: a qualitative study of young people's views of their local health service
Authors: Curtis Katherine , Liabo Kristin , Roberts Helen , Barker Maggie
Published: April 2004

Objectives  The objective of this study was to identify what children and young people in a health district in a large urban area experience as positive – and not so positive – about their local health services, in the light of a growing expectation that users play a more central role in the design and delivery of services.

Design  A qualitative study incorporating a range of methods, including interviews, play techniques and a website.

Setting  Schools, nurseries, community groups, in‐ and outpatient settings in an inner London health authority.

Participants  Young people aged between 4 and 19 years, from community (n = 92) and clinical (n = 57) settings. This included ‘hard‐to‐reach’ children, including those leaving care, those in touch with the criminal justice system, asylum seekers, and those with learning disabilities.

Results  Alongside planning and environment issues, young people particularly emphasized the impact of communication and relationships with staff on their experience of health services.

Discussion and conclusions  Using a range of flexible and age‐appropriate techniques, young people, even those as young as 4 or 5, are able to comment helpfully on their experiences of service provision. What children had to say is revealing but not astonishing to those working in the National Health Service (NHS). Clinicians and managers, to whom our findings were fed back, made this clear. If we have known for so long that the issues raised here are problems, why are we so poor at acting on this knowledge? The authors suggest four explanations.
Ensuring Quality Information for Patients: development and preliminary validation of a new instrument to improve the quality of written health care information
Authors: Moult Beki , Franck Linda S , Brady Helen
Published: April 2004

Background  Despite the recent focus on improving the quality of patient information, there is no rigorous method of assessing quality of written patient information that is applicable to all information types and that prescribes the action that is required following evaluation.

Objective  The aims of this project were to develop a practical measure of the presentation quality for all types of written health care information and to provide preliminary validity and reliability of the measure in a paediatric setting.

Methods  The Ensuring Quality Information for Patients (EQIP) tool was developed through a process of item generation, testing for concurrent validity, inter‐rater reliability and utility. Patient information managers and health care professionals tested EQIP in three annual audits of health care leaflets produced by a children's hospital.

Results  The final tool comprised 20 items. Kendall's τ B rank correlation between EQIP and DISCERN was 0.56 (P = 0.001). There was strong agreement between intuitive rating and the EQIP score (Kendall's τ B = 0.78, P = 0.009). Internal consistency using Cronbach's α was 0.80. There was good agreement between pairs of raters (mean κ = 0.60; SD = 0.18) with no differences based on types of leaflets. Audits showed significant improvement in the number of leaflets achieving a higher quality EQIP rating over a 3‐year period.

Conclusions  EQIP demonstrated good preliminary validity, reliability and utility when used by patient information managers and healthcare professionals for a wide variety of written health care information. EQIP uniquely identifies actions to be taken as a result of the quality assessment. Use of EQIP improved the quality of written health care information in a children's hospital. Wider evaluation of EQIP with written information for other populations and settings is recommended.
Misfolding of the Prion Protein at the Plasma Membrane Induces Endocytosis, Intracellular Retention and Degradation
Authors: Kiachopoulos Sophia , Heske Johanna , Tatzelt Jörg , Winklhofer Konstanze F.
Published: April 2004

Suramin induces misfolding of the cellular prion protein (PrPC) and interferes with the propagation of infectious scrapie prions. A mechanistic analysis of this effect revealed that suramin‐induced misfolding occurs at the plasma membrane and is dependent on the proximal region of the C‐terminal domain (aa 90–158) of PrPC. The conformational transition induces rapid internalization, mediated by the unstructured N‐terminal domain, and subsequent intracellular degradation of PrPC. As a consequence, PrPΔN adopts a misfolded conformation at the plasma membrane; however, internalization is significantly delayed. We also found that misfolding and intracellular retention of PrPC can be induced by copper and that, moreover, copper interferes with the propagation of the pathogenic prion protein (PrPSc) in scrapie‐infected N2a cells. Our study revealed a quality control pathway for aberrant PrP conformers present at the plasma membrane and identified distinct PrP domains involved.
Rab GTPases and Myosin Motors in Organelle Motility
Authors: Seabra Miguel C. , Coudrier Evelyne
Published: April 2004

The actin cytoskeleton is essential to ensure the proper location of, and communication between, intracellular organelles. Some actin‐based myosin motors have been implicated in this process, particularly members of the class V myosins. We discuss here the emerging role of the Ras‐like GTPases of the Rab family as regulators of myosin function in organelle transport. Evidence from yeast secretory vesicles and mitochondria, and mammalian melanosomes and endosomes suggests that Rab GTPases are crucial components of the myosin organelle receptor machinery. Better understood is the case of the melanosome where Rab27a recruits a specific effector called melanophilin, which in turn binds myosin Va. The presence of a linker protein between a Rab and a myosin may represent a general mechanism. We argue that Rabs are ideally suited to perform this role as they are exquisite organelle markers. Furthermore, the molecular switch property of Rabs may enable them to regulate the timing of the myosin association with the target organelle.