Psychopharmacological characterisation of the successive negative contrast effect in rats

Rationale Successive negative contrast (SNC) describes a change in the behaviour of an animal following a downshift in the quantitative or qualitative value of an expected reward. This behavioural response has been hypothesised to be linked to affective state, with negative states associated with larger and/or prolonged shifts in behaviour. Objective This study has investigated whether different psychopharmacological treatments have dissociable actions on the SNC effect in rats and related these findings to their actions on different neurotransmitter systems and affective state. Methods Animals were trained to perform a nose-poke response to obtain a high-value food reward (four pellets). SNC was quantified during devalue sessions in which the reward was reduced to one pellet. Using a within-subject study design, the effects of acute treatment with anxiolytic, anxiogenic, antidepressant and dopaminergic drugs were investigated during both baseline (four pellets) or devalue sessions (one pellet). Results The indirect dopamine agonist, amphetamine, attenuated the SNC effect whilst the D1/D2 antagonist, alpha-flupenthixol, potentiated it. The antidepressant citalopram, anxiolytic buspirone and anxiogenic FG7142 had no specific effects on SNC, although FG7142 induced general impairments at higher doses. The α2-adrenoceptor antagonist, yohimbine, increased premature responding but had no specific effect on SNC. Results for the anxiolytic diazepam were mixed with one group showing an attenuation of the SNC effect whilst the other showed no effect. Conclusions These data suggest that the SNC effect is mediated, at least in part, by dopamine signalling. The SNC effect may also be attenuated by benzodiazepine anxiolytics

Entanglement-free Heisenberg-limited phase estimation

Measurement underpins all quantitative science. A key example is the measurement of optical phase, used in length metrology and many other applications. Advances in precision measurement have consistently led to important scientific discoveries. At the fundamental level, measurement precision is limited by the number N of quantum resources (such as photons) that are used. Standard measurement schemes, using each resource independently, lead to a phase uncertainty that scales as 1/sqrt(N) - known as the standard quantum limit. However, it has long been conjectured that it should be possible to achieve a precision limited only by the Heisenberg uncertainty principle, dramatically improving the scaling to 1/N. It is commonly thought that achieving this improvement requires the use of exotic quantum entangled states, such as the NOON state. These states are extremely difficult to generate. Measurement schemes with counted photons or ions have been performed with N <= 6, but few have surpassed the standard quantum limit and none have shown Heisenberg-limited scaling. Here we demonstrate experimentally a Heisenberg-limited phase estimation procedure. We replace entangled input states with multiple applications of the phase shift on unentangled single-photon states. We generalize Kitaev's phase estimation algorithm using adaptive measurement theory to achieve a standard deviation scaling at the Heisenberg limit. For the largest number of resources used (N = 378), we estimate an unknown phase with a variance more than 10 dB below the standard quantum limit; achieving this variance would require more than 4,000 resources using standard interferometry. Our results represent a drastic reduction in the complexity of achieving quantum-enhanced measurement precision.Comment: Published in Nature. This is the final versio

Using Electronic Technology to Improve Clinical Care -- Results from a Before-after Cluster Trial to Evaluate Assessment and Classification of Sick Children According to Integrated Management of Childhood Illness (IMCI) Protocol in Tanzania.

Poor adherence to the Integrated Management of Childhood Illness (IMCI) protocol reduces the potential impact on under-five morbidity and mortality. Electronic technology could improve adherence; however there are few studies demonstrating the benefits of such technology in a resource-poor settings. This study estimates the impact of electronic technology on adherence to the IMCI protocols as compared to the current paper-based protocols in Tanzania. In four districts in Tanzania, 18 clinics were randomly selected for inclusion. At each site, observers documented critical parts of the clinical assessment of children aged 2 months to 5 years. The first set of observations occurred during examination of children using paper-based IMCI (pIMCI) and the next set of observations occurred during examination using the electronic IMCI (eIMCI). Children were re-examined by an IMCI expert and the diagnoses were compared. A total of 1221 children (671 paper, 550 electronic) were observed. For all ten critical IMCI items included in both systems, adherence to the protocol was greater for eIMCI than for pIMCI. The proportion assessed under pIMCI ranged from 61% to 98% compared to 92% to 100% under eIMCI (p < 0.05 for each of the ten assessment items). Use of electronic systems improved the completeness of assessment of children with acute illness in Tanzania. With the before-after nature of the design, potential for temporal confounding is the primary limitation. However, the data collection for both phases occurred over a short period (one month) and so temporal confounding was expected to be minimal. The results suggest that the use of electronic IMCI protocols can improve the completeness and consistency of clinical assessments and future studies will examine the long-term health and health systems impact of eIMCI

Changing homelessness services: revanchism, 'professionalisation' and resistance

This paper argues that the increasing international salience of homelessness can be partially explained by reference to the revanchist thesis (involving processes of coerced exclusion and abjection), but the situation on the ground is more complex. It reports on interviews with 18 representatives of 11 homelessness service providers in one city in England. As Cloke et al. found, these providers tended to be either larger, more 'professional', 'insider' services or smaller, more 'amateur', 'outsider' services. However, this does not mean that the former were necessarily more revanchist and the latter less so. Rather, the actions of both types of organisation could, in some cases, be construed as both advancing and counteracting a revanchist project

The effect of sea temperature and food availability on the spawning success of Cape Anchovy engraulis capensis in the Southern Benguela

Data on the thermal structure, copepod biomass and production, and total number of eggs of the Cape anchovy Engraulis capensis were obtained from monthly surveys during the periods August 1993 – March1994 and September 1994 – March 1995 on the western Agulhas Bank and off the South-Western Cape, South Africa. Previous work suggested that anchovy spawn on the western Agulhas Bank in temperaturesbetween 16 and 19°C, where they feed predominantly on copepods. This study shows that the western Bank is a more suitable spawning area for anchovy, having greater thermal stability, a larger area of 16–19°Cwater and a more consistent food environment than off the South-Western Cape. Also, copepod production on the western Bank was highest in 16–19°C water. To identify factors controlling the area of this watermass, a cluster analysis was used on a suite of hydrographic variables. Three periods were identified: winter (August-September), spring (October-December) and summer (January-March), reflecting changes in theextent of the 16–19°C water and anchovy spawning, both of which peaked during spring. Spring was further characterized by infrequent surface upwelling. During summer, upwelling frequently reached the surface andthe upwelling front migrated offshore, constricting the area of 16–19°C water. It is hypothesized that spawning success in anchovy is dependent upon the extent of suitable spawning habitat, both spatially (16–19°Cwater) and temporally (spring). To put this concept into a predictive framework, the number of anchovy eggs was regressed against the area of 16–19°C water; a significant, positive relationship (p < 0.001, r2 = 0.56, n = 17) was found. An implication of the hypothesis is that the duration of spawning may be important to recruitment

Process modelling of protein crystallisation: A case study of lysozyme

With the rise in interest of protein crystallisation as a purification step in downstream processing, there is significant interest in the process modelling of these crystallisation steps. Herein, we demonstrate and compare the applicability of “traditional” nucleation and growth models, commonly used to model small molecule crystallisation, for the successful population balance modelling of lysozyme crystallisation at the 100 mL and 1 L scales. Results show that both empirical power-law and first-principles models for nucleation and growth provide good fits to experimental data. Results from parameter estimation highlight a high degree of model sensitivity to initial guesses and stress the importance of providing particle size estimates in order to extract sensible data from the models. Estimates obtained for the 100 mL scale provided suitable initial guesses for the 1 L scale, despite significant differences in the final values obtained at each scale. For future work, further investigation into model validation upon scale-up is recommended. The work performed demonstrates the effectiveness of population balance modelling in the prediction of protein crystallisation behaviour, regardless of the underlying physical phenomena

Ambiguity in practice? Carers' roles in personalised social care in England

Carers play an ambiguous role within the personalisation paradigm currently shaping adult social care practice in England. Although carers have rights to assessments and support in their own right, these rights sit uneasily alongside the practices of assessment, support planning and personal budget (PB) allocation for older and disabled people. This paper reports how 14 dyads of older and learning disabled people with cognitive and/or communication impairments and their carers viewed the roles - desired and actual - played by carers in PBs. Interviews with carers and with older and disabled people were conducted during 2012 as part of a wider study into carers' roles in assessment, support planning and managing PBs. The interviews complemented a survey of reported practice in two English regions - interviews with adult social care services senior managers and focus groups with front-line care managers. Talking Mats(c) were used to support interviews with some service users. Interviews were transcribed and data analysed using the Framework approach. The interviews indicated that carers played important roles in service users' assessments and support planning, but were less likely to report receiving assessments or support of their own. While carers had the potential to benefit from PBs and support arrangements for service users, this did not reflect practice that aimed to enhance choice and control for carers. The paper draws on Twigg's typology of service conceptualisations of family carers and concludes that, despite the important social rights won by carers in England, current practice continues to regard carers primarily as a resource or a co-worker, rather than a co-client

A cardinal role for cathepsin D in co-ordinating the host-mediated apoptosis of macrophages and killing of pneumococci

The bactericidal function of macrophages against pneumococci is enhanced by their apoptotic demise, which is controlled by the anti-apoptotic protein Mcl-1. Here, we show that lysosomal membrane permeabilization (LMP) and cytosolic translocation of activated cathepsin D occur prior to activation of a mitochondrial pathway of macrophage apoptosis. Pharmacological inhibition or knockout of cathepsin D during pneumococcal infection blocked macrophage apoptosis. As a result of cathepsin D activation, Mcl-1 interacted with its ubiquitin ligase Mule and expression declined. Inhibition of cathepsin D had no effect on early bacterial killing but inhibited the late phase of apoptosis-associated killing of pneumococci in vitro. Mice bearing a cathepsin D-/- hematopoietic system demonstrated reduced macrophage apoptosis in vivo, with decreased clearance of pneumococci and enhanced recruitment of neutrophils to control pulmonary infection. These findings establish an unexpected role for a cathepsin D-mediated lysosomal pathway of apoptosis in pulmonary host defense and underscore the importance of apoptosis-associated microbial killing to macrophage function

Gastroenterologist perceptions of faecal microbiota transplantation

© 2015 Baishideng Publishing Group Inc. All rights reserved. AIM: To explore gastroenterologist perceptions towards and experience with faecal microbiota transplantation (FMT). METHODS: A questionnaire survey consisting of 17 questions was created to assess gastroenterologists' attitude towards and experience with FMT. This was anonymously distributed in hard copy format amongst attendees at gastroenterology meetings in Australia between October 2013 and April 2014. Basic descriptive statistical analyses were performed. RESULTS: Fifty-two clinicians participated. Twenty one percent had previously referred patients for FMT, 8% more than once. Ninety percent would refer patients with Clostridium difficile infection (CDI) for FMT if easily available, 37% for ulcerative colitis, 13% for Crohn's disease and 6% for irritable bowel syndrome. Six percent would not refer any indication, including recurrent CDI. Eighty-six percent would enroll patients in FMT clinical trials. Thirty-seven percent considered the optimal mode of FMT administration transcolonoscopic, 17% nasoduodenal, 13% enema and 8% oral capsule. The greatest concerns regarding FMT were: 42% lack of evidence, 12% infection risk, 10% non infectious adverse effects/lack of safety data, 10% aesthetic, 10% lack of efficacy, 4% disease exacerbation, and 2% inappropriate use; 6% had no concerns. Seventy seven percent believed there is a lack of accessibility while 52% had an interest in learning how to provide FMT. Only 6% offered FMT at their institution. CONCLUSION: Despite general enthusiasm, most gastroenterologists have limited experience with, or access to, FMT. The greatest concerns were lack of supportive evidence and safety issues. However a significant proportion would refer indications other than CDI for FMT despite insufficient evidence. These data provide guidance on where education and training are required