The multidimensional measurement of the positive symptoms of psychosis

The measures most frequently used to assess psychotic symptoms fail to reflect important dimensions. The Psychotic Symptom Rating Scale (PSYRATS) aims to capture the multidimensional nature of auditory hallucinations and delusions. Individuals (N = 276) who had recently relapsed with positive symptoms completed the auditory hallucinations and delusions PSYRATS scales. These scores were compared with the relevant items from the SAPS and PANSS, and with measures of current mood. Total scores and distribution of items of the PSYRATS scales are presented and correlated with other measures. Positive symptom items from the SAPS and PANSS reflected the more objective aspects of PSYRATS ratings of auditory hallucinations and delusions (frequency and conviction) but were relatively poor at measuring distress. A major strength of the PSYRATS scales is the specific measurement of the distress dimension of symptoms, which is a key target of psychological intervention. It is advised that the PSYRATS should not be used as a total score alone, whilst further research is needed to clarify the best use of potential subscales. Copyright (c) 2007 John Wiley & Sons, Ltd.

Investigating the mechanisms underlying neuronal death in ischemia using in vitro oxygen-glucose deprivation: potential involvement of protein SUMOylation

It is well established that brain ischemia can cause neuronal death via different signaling cascades. The relative importance and interrelationships between these pathways, however, remain poorly understood. Here is presented an overview of studies using oxygen-glucose deprivation of organotypic hippocampal slice cultures to investigate the molecular mechanisms involved in ischemia. The culturing techniques, setup of the oxygen-glucose deprivation model, and analytical tools are reviewed. The authors focus on SUMOylation, a posttranslational protein modification that has recently been implicated in ischemia from whole animal studies as an example of how these powerful tools can be applied and could be of interest to investigate the molecular pathways underlying ischemic cell death.

Enhanced sensitivity to rapamycin following long-term oestrogen deprivation in MCF-7, T-47-D and ZR-75-1 human breast cancer cells

Human breast cancer cells (MCF-7, T-47-D and ZR-75-1) can adapt to circumvent any reduced growth rate during long-term oestrogen deprivation, and this provides three model systems to investigate mechanisms of endocrine resistance in breast cancer. In this paper we report consistent differences in the effects of three growth inhibitors following long-term oestrogen deprivation in all three cell models. Long-term oestrogen deprivation of MCF-7, T-47-D and ZR-75-1 cells resulted in reduced growth inhibition by PD98059 (2–10 µg/ml), implying a loss of dependence on mitogen-activated protein kinase pathways for growth. The growth inhibitor LY294002 (2–10 µM) inhibited growth of both oestrogen-maintained and oestrogen-deprived cells with similar dose–responses, implying continued similar dependence on phosphoinositide 3-kinase (PI3K) pathways with no alteration after adaptation to oestrogen independent growth. However, by contrast, long-term oestrogen deprivation resulted in an increased sensitivity to growth inhibition by rapamycin, which was not reduced by readdition of oestradiol. The enhanced inhibition of long-term oestrogen-deprived MCF-7-ED, T-47-D-ED and ZR-75-1-ED cell growth by combining rapamycin with LY294002 at concentrations where each alone had little effect, offers preclinical support to the development of therapeutic combinations of rapamycin analogues with other PI3K inhibitors in endocrine-resistant breast cancer.

Crosstalk with insulin and dependence on PI3K/Akt/mTOR rather than MAPK pathways in upregulation of basal growth following long-term oestrogen deprivation in three human breast cancer cell lines

Background: MCF-7, T-47-D, ZR-75-1 human breast cancer cell lines are dependent on oestrogen for growth but can adapt to grow during long-term oestrogen deprivation. This serves as a model for identification of therapeutic targets in endocrine-resistant breast cancer. Methods: An overlooked complication of this model is that it involves more than non-addition of oestrogen, and inadequate attention has been given to separating molecular events associated with each of the culture manipulations. Results: Insulin and oestradiol were shown to protect MCF-7 cells against upregulation of basal growth, demonstrating a crosstalk in the growth adaptation process. Increased phosphorylation of p44/42MAPK and c-Raf reflected removal of insulin from the medium and proliferation of all three cell lines was inhibited to a lesser extent by PD98059 and U0126 following long-term oestrogen/insulin withdrawal, demonstrating a reduced dependence on the MAPK pathway. By contrast, long-term oestrogen/insulin deprivation did not alter levels of phosphorylated Akt and did not alter the dose-response of growth inhibition with LY294002 in any of the three cell lines. The IGF1R inhibitor picropodophyllin inhibited growth of all MCF-7 cells but only in the long-term oestrogen/insulin-deprived cells was this paralleled by reduction in phosphorylated p70S6K, a downstream target of mTOR. Long-term oestrogen/insulin-deprived MCF-7 cells had higher levels of phosphorylated p70S6K and developed increased sensitivity to growth inhibition by rapamycin. Conclusions: The greater sensitivity to growth inhibition by rapamycin in all three cell lines following long-term oestrogen/insulin deprivation suggests rapamycin-based therapies might be more effective in breast cancers with acquired oestrogen resistance. Keywords Akt, breast cancer cells, endocrine resistance, insulin, MAPK, MCF-7 cells, mTOR, oestrogen, oestrogen-deprived, PI3K, picropodophyllin, rapamycin, T-47-D cells, ZR-75-1 cells

The shape of change: memetic analysis of poverty definitions from the 1970s to the 2000s

The authors illustrate how notions of poverty are constructed around specific ‘memes’, or replicating units of cultural information, around which concepts and ideas develop and change. Three ‘memes’ characterising definitions of poverty over the previous years were identified: ‘basic needs’, ‘multidimensional’ and ‘deprivation’. The analysis illustrated the semantic space in which each term was utilised and to the extent it changed and modified over time by different actors. The results revealed how ‘memes’ compete with one another across the discourse. Within this competition, older concepts are almost never fully abandoned, but rather repackaged and reutilised. Thus, new definitions of poverty are less innovative than portrayed in the wider literature.

Oxygen/Glucose deprivation induces a reduction in synaptic AMPA receptors on hippocampal CA3 neurons mediated by mGluR1 and adenosine A3 receptors

Hippocampal CA1 pyramidal neurons are highly sensitive to ischemic damage, whereas neighboring CA3 pyramidal neurons are less susceptible. It is proposed that switching of AMPA receptor (AMPAR) subunits on CA1 neurons during an in vitro model of ischemia, oxygen/glucose deprivation (OGD), leads to an enhanced permeability of AMPARs to Ca2+, resulting in delayed cell death. However, it is unclear whether the same mechanisms exist in CA3 neurons and whether this underlies the differential sensitivity to ischemia. Here, we investigated the consequences of OGD for AMPAR function in CA3 neurons using electrophysiological recordings in rat hippocampal slices. Following a 15 min OGD protocol, a substantial depression of AMPAR-mediated synaptic transmission was observed at CA3 associational/commissural and mossy fiber synapses but not CA1 Schaffer collateral synapses. The depression of synaptic transmission following OGD was prevented by metabotropic glutamate receptor 1 (mGluR1) or A3 receptor antagonists, indicating a role for both glutamate and adenosine release. Inhibition of PLC, PKC, or chelation of intracellular Ca2+ also prevented the depression of synaptic transmission. Inclusion of peptides to interrupt the interaction between GluA2 and PICK1 or dynamin and amphiphysin prevented the depression of transmission, suggesting a dynamin and PICK1-dependent internalization of AMPARs after OGD. We also show that a reduction in surface and total AMPAR protein levels after OGD was prevented by mGluR1 or A3 receptor antagonists, indicating that AMPARs are degraded following internalization. Thus, we describe a novel mechanism for the removal of AMPARs in CA3 pyramidal neurons following OGD that has the potential to reduce excitotoxicity and promote neuroprotection

Influence of colostrum deprivation and concurrent Cryptosporidium parvum infection on the colonization and persistence of Escherichia coli O157:H7 in young lambs

Escherichia coli O157: H7 and Cryptosporidium parvum infections of man have been associated with direct contact with small ruminants. Colostrum protects neonates against gastrointestinal pathogens, and orphan lambs, which are common on petting farms, may be deprived of this protection. In a recent study, it was demonstrated that high shedding of E coli O157 : H7 by an 8-week-old goat kid was associated with coincidental C. parvum infection. Furthermore, both pathogens were co-located in the distal gastrointestinal tract. It was hypothesized that colostrum deprivation and pre-infection with C. parvum predisposed young ruminants to colonization and increased shedding of E coli O157: H7. To test this, 21 lambs 5 weeks of age were divided into four groups as follows: (A) colostrum-deprived and inoculated with E coli O157: H7, (B) colostrum-deprived and inoculated with C. parvum and then E coli O157: H7, (C) conventionally reared and inoculated with E coli O157: H7, (D) conventionally reared and inoculated with C. parvum and then E coli O15 7: H7. C. parvum was detected between 8 and 12 days post-inoculation in most of the infected lambs. At 24 h post-inoculation with E coli O157: H7, all lambs were shedding between 5 x 10(4) and 5 x 10(7) c.f.u. E coli O157: H7 per gram of faeces. E coli O157: H7 was shed in higher numbers in the groups pre-inoculated with C. parvum, whether conventionally reared or colostrum-deprived. Interestingly, for the colostrum-deprived lambs on day 3, a significant difference in shedding of E coli O157: H7 was observed (P= 0-038), with the lambs inoculated with E coli alone yielding higher counts than those pre-inoculated with C. parvum. From day 15 onwards, shedding of E coli O157: H7 was highest from the colostrum-deprived C. parvum-infected lambs, then (in descending order of shedding) the colostrum-deprived lambs, the conventionally reared lambs infected with C. parvum, and the conventionally reared animals. In total, four animals were euthanized, two at 24 h and two at 96 h post inoculation with E coli 0 157: H7 (two conventionally reared and two colostrum-deprived). All animals euthanized were from groups pre-inoculated with C. parvum prior to challenge with E coli O157 : H7. On examination of tissues, in three of the four animals examined, multifocal attaching and effacing lesions were observed in the caecum, colon, rectum and at the recto-anal junction, and were confirmed by immunolhistochemistry to be associated with E coli O157: H7.

A Web Map Service implementation for the visualization of multidimensional gridded environmental data

We describe ncWMS, an implementation of the Open Geospatial Consortium’s Web Map Service (WMS) specification for multidimensional gridded environmental data. ncWMS can read data in a large number of common scientific data formats – notably the NetCDF format with the Climate and Forecast conventions – then efficiently generate map imagery in thousands of different coordinate reference systems. It is designed to require minimal configuration from the system administrator and, when used in conjunction with a suitable client tool, provides end users with an interactive means for visualizing data without the need to download large files or interpret complex metadata. It is also used as a “bridging” tool providing interoperability between the environmental science community and users of geographic information systems. ncWMS implements a number of extensions to the WMS standard in order to fulfil some common scientific requirements, including the ability to generate plots representing timeseries and vertical sections. We discuss these extensions and their impact upon present and future interoperability. We discuss the conceptual mapping between the WMS data model and the data models used by gridded data formats, highlighting areas in which the mapping is incomplete or ambiguous. We discuss the architecture of the system and particular technical innovations of note, including the algorithms used for fast data reading and image generation. ncWMS has been widely adopted within the environmental data community and we discuss some of the ways in which the software is integrated within data infrastructures and portals.

Asymptotic behavior at infinity of solutions of multidimensional second kind integral equations

We consider second kind integral equations of the form x(s) - (abbreviated x - K x = y ), in which Ω is some unbounded subset of Rn. Let Xp denote the weighted space of functions x continuous on Ω and satisfying x (s) = O(|s|-p ),s → ∞We show that if the kernel k(s,t) decays like |s — t|-q as |s — t| → ∞ for some sufficiently large q (and some other mild conditions on k are satisfied), then K ∈ B(XP) (the set of bounded linear operators on Xp), for 0 ≤ p ≤ q. If also (I - K)-1 ∈ B(X0) then (I - K)-1 ∈ B(XP) for 0 < p < q, and (I- K)-1∈ B(Xq) if further conditions on k hold. Thus, if k(s, t) = O(|s — t|-q). |s — t| → ∞, and y(s)=O(|s|-p), s → ∞, the asymptotic behaviour of the solution x may be estimated as x (s) = O(|s|-r), |s| → ∞, r := min(p, q). The case when k(s,t) = к(s — t), so that the equation is of Wiener-Hopf type, receives especial attention. Conditions, in terms of the symbol of I — K, for I — K to be invertible or Fredholm on Xp are established for certain cases (Ω a half-space or cone). A boundary integral equation, which models three-dimensional acoustic propaga-tion above flat ground, absorbing apart from an infinite rigid strip, illustrates the practical application and sharpness of the above results. This integral equation mod-els, in particular, road traffic noise propagation along an infinite road surface sur-rounded by absorbing ground. We prove that the sound propagating along the rigid road surface eventually decays with distance at the same rate as sound propagating above the absorbing ground.

Near-optimal mean value estimates for multidimensional Weyl sums

We obtain sharp estimates for multidimensional generalisations of Vinogradov’s mean value theorem for arbitrary translation-dilation invariant systems, achieving constraints on the number of variables approaching those conjectured to be the best possible. Several applications of our bounds are discussed.

A multidimensional comparison of discourse organization in English and Chinese university students' argumentative writing

Three methodological limitations in English-Chinese contrastive rhetoric research have been identified in previous research, namely: the failure to control for the quality of L1 data; an inference approach to interpreting the relationship between L1 and L2 writing; and a focus on national cultural factors in interpreting rhetorical differences. Addressing these limitations, the current study examined the presence or absence and placement of thesis statement and topic sentences in four sets of argumentative texts produced by three groups of university students. We found that Chinese students tended to favour a direct/deductive approach in their English and Chinese writing, while native English writers typically adopted an indirect/inductive approach. This study argues for a dynamic and ecological interpretation of rhetorical practices in different languages and cultures.

The CURE scale: a multidimensional measure of service recovery strategy

Purpose – This paper aims to address the gaps in service recovery strategy assessment. An effective service recovery strategy that prevents customer defection after a service failure is a powerful managerial instrument. The literature to date does not present a comprehensive assessment of service recovery strategy. It also lacks a clear picture of the service recovery actions at managers’ disposal in case of failure and the effectiveness of individual strategies on customer outcomes. Design/methodology/approach – Based on service recovery theory, this paper proposes a formative index of service recovery strategy and empirically validates this measure using partial least-squares path modelling with survey data from 437 complainants in the telecommunications industry in Egypt. Findings – The CURE scale (CUstomer REcovery scale) presents evidence of reliability as well as convergent, discriminant and nomological validity. Findings also reveal that problem-solving, speed of response, effort, facilitation and apology are the actions that have an impact on the customer’s satisfaction with service recovery. Practical implications – This new formative index is of potential value in investigating links between strategy and customer evaluations of service by helping managers identify which actions contribute most to changes in the overall service recovery strategy as well as satisfaction with service recovery. Ultimately, the CURE scale facilitates the long-term planning of effective complaint management. Originality/value – This is the first study in the service marketing literature to propose a comprehensive assessment of service recovery strategy and clearly identify the service recovery actions that contribute most to changes in the overall service recovery strategy.

The multidimensional character of accounting numbers

This paper takes as its motivation debates surrounding the multiplicity of functions of accounting information. We are in particular interested in the existential function of accounting numbers and argue that numerical signs having discursive possibilities may acquire new meanings through reframing. Drawing on Goffman’s (1974) frame analysis and Vollmer’s (2007) work on three-dimensional character of numerical signs, we explore the ways in which numbers can go through instantaneous transformations and tell a new kind of story. In our analysis, we look at the main historical developments and current controversies surrounding accounting practice with a specific focus on scandals involving numerical signs as moments where our understandings and the discursive function of previously inoffensive signs shifts through a collective involvement. We map the purpose and usefulness of Vollmer’s three-dimensional framework in the analysis of selected financial accounting practices and scandals as examples of instances where numbers are reframed to suddenly perform a different existential function in context of their calculative and symptomatic dimensions.