A behavioural and electrophysiological study of factors involved in the relationship between stress and alcohol dependence

Alcohol dependence causes disruption to both work and family life and the associated costs are £150+ million in the UK alone. Stressful life events play a role in initiation of uncontrolled (dependent) drinking and can precipitate relapse to high ethanol consumption after treatment / abstinence. The primary neurological substrate for ethanol reward is the mesolimbic dopamine system of the medial forebrain bundle. Activation of the hypothalamopituitaryadrenal axis (the hormonal response to many stresssors) plays a role in the control of ethanol consumption and relapse, and modulation of neuronal activity by chronic calcium channel blockade decreases ethanol intake, tolerance and withdrawal. The stress system and calcium channel blockade both affect the dopaminergic reward pathways. Hypothesis: Stress and the stress hormone, corticosterone, play a crucial role in the modulation of ethanol consumption and the long term changes resulting from chronic ethanol intake. This hypothesis was tested by investigating the effects of:• social status and calcium channel blockade on chronic ethanol intake (free choice 5, 10, 20% ethanol and water) of group housed rats.• social stress from defeat by an aggressive resident on ethanol preference of low ethanol preference C57 mice.• 6 days abstinence from chronic ethanol intake (liquid diet) on NMDA-stimulated firing of dopaminergic, ventral tegmental area, cells and the role of corticosterone in modulation of this response to NMDA. The main findings from these studies indicate that, while the social stress of group housing under laboratory conditions may be insufficient to elevate ethanol intake, repeated defeat significantly increases ethanol intake. However, neither chronic ethanol consumption nor corticosterone seemd to have any effect on NMDA-stimulated dopamine cell firing. These results indicate a significant role for social stress in the modulation of ethanol intake but possibly not via the action of corticosterone on NMDA-stimulation of the mesolimbic dopamine system

Wet Paint: Visual Culture in a Changing Britain – A Round Table Debate

Political decisions and debates regarding the interregional and interna- tional partnerships that constitute Great Britain, including those over Scottish Independence, EVEL (English Votes for English Laws) and proposed legislation on an ‘in/out’ referendum on British membership of the European Union, have contributed to, and intensified, the examination of Britain’s institutions, as well as its national emblems and arche- types. In light of such a dynamic situation, Visual Culture in Britain has asked representatives of British universities, the museum sector and research centres to respond to the idea of a changing Britain through the prism of British art and visual culture, using cogent examples wherever possible, and to outline their observations, understandings and positions within this rapidly developing context

When rats rescue robots

Robots are increasingly being used to monitor and even participate in social interactions with animals in their own environments. Robotic animals enable social behaviors to be observed in natural environments, or specifically elicited under the control of an experimenter. It is an open question to what extent animals will form positive social connections with such robots. To test this, we familiarized rats to two rat-sized robots, one exhibiting “social” behaviors, including helping, while the other was also mobile but not helpful. When given an opportunity to release the robots from restrainers, as they do for conspecifics, we found that rats did release the robots, and moreover, were significantly more likely to release the helpful than the unhelpful robot. These findings indicate that robots can elicit helpful behavior from rats, and that rats will even discriminate between robots on the basis of their behaviors

Patterns of Selection in Anti-Malarial Immune Genes in Malaria Vectors: Evidence for Adaptive Evolution in LRIM1 in Anopheles arabiensis

Co-evolution between Plasmodium species and its vectors may result in adaptive changes in genes that are crucial components of the vector's defense against the pathogen. By analyzing which genes show evidence of positive selection in malaria vectors, but not in closely related non-vectors, we can identify genes that are crucial for the mosquito's resistance against Plasmodium.We investigated genetic variation of three anti-malarial genes; CEC1, GNBP-B1 and LRIM1, in both vector and non-vector species of the Anopheles gambiae complex. Whereas little protein differentiation was observed between species in CEC1 and GNBP-B1, McDonald-Kreitman and maximum likelihood tests of positive selection show that LRIM1 underwent adaptive evolution in a primary malaria vector; An. arabiensis. In particular, two adjacent codons show clear signs of adaptation by having accumulated three out of four replacement substitutions. Furthermore, our data indicate that this LRIM1 allele has introgressed from An. arabiensis into the other main malaria vector An. gambiae.Although no evidence exists to link the adaptation of LRIM1 to P. falciparum infection, an adaptive response of a known anti-malarial gene in a primary malaria vector is intriguing, and may suggest that this gene could play a role in Plasmodium resistance in An. arabiensis. If so, our data also predicts that LRIM1 alleles in An. gambiae vary in their level of resistance against P. falciparum

Extinction filters mediate the global effects of habitat fragmentation on animals

Habitat loss is the primary driver of biodiversity decline worldwide, but the effects of fragmentation (the spatial arrangement of remaining habitat) are debated. We tested the hypothesis that forest fragmentation sensitivity—affected by avoidance of habitat edges—should be driven by historical exposure to, and therefore species’ evolutionary responses to disturbance. Using a database containing 73 datasets collected worldwide (encompassing 4489 animal species), we found that the proportion of fragmentation-sensitive species was nearly three times as high in regions with low rates of historical disturbance compared with regions with high rates of disturbance (i.e., fires, glaciation, hurricanes, and deforestation). These disturbances coincide with a latitudinal gradient in which sensitivity increases sixfold at low versus high latitudes. We conclude that conservation efforts to limit edges created by fragmentation will be most important in the world’s tropical forests

Investigation of rheumatoid arthritis susceptibility loci in juvenile idiopathic arthritis confirms high degree of overlap

<p>Objectives: Rheumatoid arthritis (RA) shares some similar clinical and pathological features with juvenile idiopathic arthritis (JIA); indeed, the strategy of investigating whether RA susceptibility loci also confer susceptibility to JIA has already proved highly successful in identifying novel JIA loci. A plethora of newly validated RA loci has been reported in the past year. Therefore, the aim of this study was to investigate these single nucleotide polymorphisms (SNP) to determine if they were also associated with JIA.</p> <p>Methods: Thirty-four SNP that showed validated association with RA and had not been investigated previously in the UK JIA cohort were genotyped in JIA cases (n=1242), healthy controls (n=4281), and data were extracted for approximately 5380 UK Caucasian controls from the Wellcome Trust Case–Control Consortium 2. Genotype and allele frequencies were compared between cases with JIA and controls using PLINK. A replication cohort of 813 JIA cases and 3058 controls from the USA was available for validation of any significant findings.</p> <p>Results: Thirteen SNP showed significant association (p<0.05) with JIA and for all but one the direction of association was the same as in RA. Of the eight loci that were tested, three showed significant association in the US cohort.</p> <p>Conclusions: A novel JIA susceptibility locus was identified, CD247, which represents another JIA susceptibility gene whose protein product is important in T-cell activation and signalling. The authors have also confirmed association of the PTPN2 and IL2RA genes with JIA, both reaching genome-wide significance in the combined analysis.</p&gt

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

Background: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. Methods: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. Findings: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96–1·28). Interpretation: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. Funding: National Institute for Health Research Health Services and Delivery Research Programme

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

BACKGROUND: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. METHODS: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. FINDINGS: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96-1·28). INTERPRETATION: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. FUNDING: National Institute for Health Research Health Services and Delivery Research Programme