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

Occupational asthma: a review.

Occupational asthma is the most common form of occupational lung disease in the developed world at the present time. In this review, the epidemiology, pathogenesis/mechanisms, clinical presentations, management, and prevention of occupational asthma are discussed. The population attributable risk of asthma due to occupational exposures is considerable. Current understanding of the mechanisms by which many agents cause occupational asthma is limited, especially for low-molecular-weight sensitizers and irritants. The diagnosis of occupational asthma is generally established on the basis of a suggestive history of a temporal association between exposure and the onset of symptoms and objective evidence that these symptoms are related to airflow limitation. Early diagnosis, elimination of exposure to the responsible agent, and early use of inhaled steroids may play important roles in the prevention of long-term persistence of asthma. Persistent occupational asthma is often associated with substantial disability and consequent impacts on income and quality of life. Prevention of new cases is the best approach to reducing the burden of asthma attributable to occupational exposures. Future research needs are identified

A surface oxidised Fe-S catalyst for the liquid phase hydrogenation of CO₂

Rapidly increasing anthropogenic carbon dioxide (CO_{2}) emissions, coupled with irreversible climate change and depleting fossil fuel reserves, have significantly increased the drive for CO_{2} utilisation. Iron sulfide as a catalyst for the hydrogenation of CO_{2} has been discussed in the literature for decades, especially in an origin-of-life context, but little experimental evidence exists in the literature for its feasibility. Here we report the catalytic properties of pyrrhotite (Fe_{1−x}S) for the hydrogenation of CO_{2} into formate. Advanced material characterisation methods in combination with computational studies have allowed us to identify surface S–Fe–O moieties as active sites for the reaction

The role of surface oxidation and Fe-Ni synergy in Fe-Ni-S catalysts for CO2 hydrogenation.

Increasing carbon dioxide (CO2) emissions, resulting in climate change, have driven the motivation to achieve the effective and sustainable conversion of CO2 into useful chemicals and fuels. Taking inspiration from biological processes, synthetic iron-nickel-sulfides have been proposed as suitable catalysts for the hydrogenation of CO2. In order to experimentally validate this hypothesis, here we report violarite (Fe,Ni)3S4 as a cheap and economically viable catalyst for the hydrogenation of CO2 into formate under mild, alkaline conditions at 125 °C and 20 bar (CO2 : H2 = 1 : 1). Calcination of violarite at 200 °C resulted in excellent catalytic activity, far superior to that of Fe-only and Ni-only sulfides. We further report first principles simulations of the CO2 conversion on the partially oxidised (001) and (111) surfaces of stoichiometric violarite (FeNi2S4) and polydymite (Ni3S4) to rationalise the experimentally observed trends. We have obtained the thermodynamic and kinetic profiles for the reaction of carbon dioxide (CO2) and water (H2O) on the catalyst surfaces via substitution and dissociation mechanisms. We report that the partially oxidised (111) surface of FeNi2S4 is the best catalyst in the series and that the dissociation mechanism is the most favourable. Our study reveals that the partial oxidation of the FeNi2S4 surface, as well as the synergy of the Fe and Ni ions, are important in the catalytic activity of the material for the effective hydrogenation of CO2 to formate

Are there gender differences in the geography of alcohol-related mortality in Scotland? An ecological study

<b>Background</b> There is growing concern about alcohol-related harm, particularly within Scotland which has some of the highest rates of alcohol-related death in western Europe. There are large gender differences in alcohol-related mortality rates in Scotland and in other countries, but the reasons for these differences are not clearly understood. In this paper, we aimed to address calls in the literature for further research on gender differences in the causes, contexts and consequences of alcohol-related harm. Our primary research question was whether the kind of social environment which tends to produce higher or lower rates of alcohol-related mortality is the same for both men and women across Scotland. <b>Methods</b> Cross-sectional, ecological design. A comparison was made between spatial variation in men's and women's age-standardised alcohol-related mortality rates in Scotland using maps, Moran's Index, linear regression and spatial analyses of residuals. Directly standardised mortality rates were derived from individual level records of death registration, 2000–2005 (n = 8685). <b>Results</b> As expected, men's alcohol-related mortality rate substantially exceeded women's and there was substantial spatial variation in these rates for both men and women within Scotland. However, there was little spatial variation in the relationship between men's and women's alcohol-mortality rates (r2 = 0.73); areas with relatively high rates of alcohol-related mortality for men tended also to have relatively high rates for women. In a small number of areas (8 out of 144) the relationship between men's and women's alcohol-related mortality rates was significantly different. <b>Conclusion</b> In as far as geographic location captures exposure to social and economic environment, our results suggest that the relationship between social and economic environment and alcohol-related harm is very similar for men and women. The existence of a small number of areas in which men's and women's alcohol-related mortality had an different relationship suggests that some places may have unusual drinking cultures. These might prove useful for further investigations into the factors which influence drinking behaviour in men and women

Emergency ambulance service involvement with residential care homes in the support of older people with dementia : an observational study

© 2014 Amador et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.BACKGROUND: Older people resident in care homes have a limited life expectancy and approximately two-thirds have limited mental capacity. Despite initiatives to reduce unplanned hospital admissions for this population, little is known about the involvement of emergency services in supporting residents in these settings.METHODS: This paper reports on a longitudinal study that tracked the involvement of emergency ambulance personnel in the support of older people with dementia, resident in care homes with no on-site nursing providing personal care only. 133 residents with dementia across 6 care homes in the East of England were tracked for a year. The paper examines the frequency and reasons for emergency ambulance call-outs, outcomes and factors associated with emergency ambulance service use. RESULTS: 56% of residents used ambulance services. Less than half (43%) of all call-outs resulted in an unscheduled admission to hospital. In addition to trauma following a following a fall in the home, results suggest that at least a reasonable proportion of ambulance contacts are for ambulatory care sensitive conditions. An emergency ambulance is not likely to be called for older rather than younger residents or for women more than men. Length of residence does not influence use of emergency ambulance services among older people with dementia. Contact with primary care services and admission route into the care home were both significantly associated with emergency ambulance service use. The odds of using emergency ambulance services for residents admitted from a relative's home were 90% lower than the odds of using emergency ambulance services for residents admitted from their own home. CONCLUSIONS: Emergency service involvement with this vulnerable population merits further examination. Future research on emergency ambulance service use by older people with dementia in care homes, should account for important contextual factors, namely, presence or absence of on-site nursing, GP involvement, and access to residents' family, alongside resident health characteristics.Peer reviewedFinal Published versio

Entanglement-enhanced probing of a delicate material system

Quantum metrology uses entanglement and other quantum effects to improve the sensitivity of demanding measurements. Probing of delicate systems demands high sensitivity from limited probe energy and has motivated the field's key benchmark-the standard quantum limit. Here we report the first entanglement-enhanced measurement of a delicate material system. We non-destructively probe an atomic spin ensemble by means of near-resonant Faraday rotation, a measurement that is limited by probe-induced scattering in quantum-memory and spin-squeezing applications. We use narrowband, atom-resonant NOON states to beat the standard quantum limit of sensitivity by more than five standard deviations, both on a per-photon and per-damage basis. This demonstrates quantum enhancement with fully realistic loss and noise, including variable-loss effects. The experiment opens the way to ultra-gentle probing of single atoms, single molecules, quantum gases and living cells.Comment: 7 pages, 8 figures; Nature Photonics, advance online publication, 16 December 201

Frequent and Persistent PLCG1 Mutations in Sezary Cells Directly Enhance PLC gamma 1 Activity and Stimulate NF kappa B, AP-1, and NFAT Signaling

Phospholipase C Gamma 1 (PLCG1) is frequently mutated in primary cutaneous T-cell lymphoma (CTCL). This study functionally interrogated nine PLCG1 mutations (p.R48W, p.S312L, p.D342N, p.S345F, p.S520F, p.R1158H, p.E1163K, p.D1165H, and the in-frame indel p.VYEEDM1161V) identified in Sézary Syndrome, the leukemic variant of CTCL. The mutations were demonstrated in diagnostic samples and persisted in multiple tumor compartments over time, except in patients who achieved a complete clinical remission. In basal conditions, the majority of the mutations confer PLCγ1 gain-of-function activity through increased inositol phosphate production and the downstream activation of NFκB, AP-1, and NFAT transcriptional activity. Phosphorylation of the p.Y783 residue is essential for the proximal activity of wild-type PLCγ1, but we provide evidence that activating mutations do not require p.Y783 phosphorylation to stimulate downstream NFκB, NFAT, and AP-1 transcriptional activity. Finally, the gain-of-function effects associated with the p.VYEEDM1161V indel suggest that the C2 domain may have a role in regulating PLCγ1 activity. These data provide compelling evidence to support the development of therapeutic strategies targeting mutant PLCγ1

Effect of Biodiversity Changes in Disease Risk: Exploring Disease Emergence in a Plant-Virus System

The effect of biodiversity on the ability of parasites to infect their host and cause disease (i.e. disease risk) is a major question in pathology, which is central to understand the emergence of infectious diseases, and to develop strategies for their management. Two hypotheses, which can be considered as extremes of a continuum, relate biodiversity to disease risk: One states that biodiversity is positively correlated with disease risk (Amplification Effect), and the second predicts a negative correlation between biodiversity and disease risk (Dilution Effect). Which of them applies better to different host-parasite systems is still a source of debate, due to limited experimental or empirical data. This is especially the case for viral diseases of plants. To address this subject, we have monitored for three years the prevalence of several viruses, and virus-associated symptoms, in populations of wild pepper (chiltepin) under different levels of human management. For each population, we also measured the habitat species diversity, host plant genetic diversity and host plant density. Results indicate that disease and infection risk increased with the level of human management, which was associated with decreased species diversity and host genetic diversity, and with increased host plant density. Importantly, species diversity of the habitat was the primary predictor of disease risk for wild chiltepin populations. This changed in managed populations where host genetic diversity was the primary predictor. Host density was generally a poorer predictor of disease and infection risk. These results support the dilution effect hypothesis, and underline the relevance of different ecological factors in determining disease/infection risk in host plant populations under different levels of anthropic influence. These results are relevant for managing plant diseases and for establishing conservation policies for endangered plant species