A quantification of the relationship between neuronal responses in the rat rostral ventromedial medulla and noxious stimulation-evoked withdrawal reflexes

The rostral ventromedial medulla (RVM) regulates a range of involuntary behaviours but is most often associated with nociception via the action of pronociceptive ON cells and antinociceptive OFF cells. The phasic responses of ON and OFF cells determine whether or not incoming noxious signals provoke a withdrawal reflex, and previous studies have suggested that reflex RVM activity patterns actively shape motor output. Here we challenged the model by using juvenile rats, which are known to exhibit markedly different reflex responses compared with adults. By recording single-cell activity in the RVM and the electromyography responses of hindlimb flexor muscles to noxious thermal stimulation we found that the juvenile reflex had a shorter onset latency, was larger in amplitude and exhibited a decreased rise time compared with the adult reflex. The responses of ON and OFF cells faithfully tracked the shorter onset latency of the reflex by also responding earlier and, thus, still preceded the reflex. However, neither the reflex amplitude nor the ongoing response profile was predicted by the firing rate of RVM cells in either age group. Instead we found a close correspondence between RVM activity and the reflex only during the initiation of the response. Furthermore, the short rise time of the juvenile reflex was reflected in higher rates of change of both ON and OFF cell firing. Our data suggest that the RVM is associated only with the initiation of reflexes and does not shape ongoing muscle activity, which is more likely to be subserved by downstream spinal processes

Improving urban management: a case study technique

With the support of OECD and UNESCO, a basic, local-level monitoring technique has been developed to aid self-learning and facilitate interna­tional exchange of urban management experience. In this article, the technique is outlined and some implications for Third World planners are discussed

Local Plan Implementation: some Case-Study Implications for Research, Training and Management

Following the 1977 OECD Athens Symposium on Urban Management, pump-priming finance was made available to Dr. John Taylor to head a small team of full and part-time researchers to examine the plan implementation process in two tightly defined case study areas in England. This project was both experimental and specula­tive, the basic aim being to indicate what the scope and limitations were of the case study approach and whether OECD could profitably further develop this work as a means of fulfilling the wider objectives of exchanging international expertise and promoting inter-disciplinary cooperation. This conference paper reports back on what has been discovered and indicates possible future research directions

The diversity of assembly histories leading to disc galaxy formation in a LambdaCDM model

[Abridged] Typical disc galaxies forming in a LambdaCDM cosmology encounter a violent environment, where they often experience mergers with massive satellites. The fact that disc galaxies are ubiquitous in the local Universe suggests that a quiescent history is not necessary for their formation. Modern cosmological simulations can now obtain relatively realistic populations of disc galaxies, but it still remains to be clarified how discs manage to survive massive mergers. Here we use a suite of high-resolution hydrodynamical simulations set in a LambdaCDM cosmology to elucidate the fate of discs encountering massive mergers. We extract a sample of approximately 100 disc galaxies and follow the changes in their post-merger morphologies, as tracked by their disc-to-total ratios (D/T). We also examine the relations between their present-day morphology, assembly history and gas fractions. We find that approximately half of present-day disc galaxies underwent at least one merger with a satellite of total mass exceeding the host system's stellar mass, a third had mergers with satellites of mass exceeding 3 times the host's stellar mass, and approximately one-sixth had mergers with satellites of mass exceeding 10 times of the host's stellar mass. These mergers lead to a sharp, but often temporary, decrease in the D/T of the hosts, implying that discs are usually disrupted but then quickly re-grow. To do so, high cold gas fractions are required post-merger, as well as a relatively quiescent recent history (over a few Gyrs before z=0). Our results show that discs can form via diverse merger pathways and that quiescent histories are not the dominant mode of disc formation

Psychosis and the level of mood incongruence in Bipolar Disorder are related to genetic liability for Schizophrenia

Abstract Importance Bipolar disorder (BD) overlaps schizophrenia in its clinical presentation and genetic liability. Alternative approaches to patient stratification beyond current diagnostic categories are needed to understand the underlying disease processes/mechanisms. Objectives To investigate the relationship between common-variant liability for schizophrenia, indexed by polygenic risk scores (PRS) and psychotic presentations of BD, using clinical descriptions which consider both occurrence and level of mood-incongruent psychotic features. Design Case-control design: using multinomial logistic regression, to estimate differential associations of PRS across categories of cases and controls. Settings & Participants 4399 BDcases, mean [sd] age-at-interview 46[12] years, of which 2966 were woman (67%) from the BD Research Network (BDRN) were included in the final analyses, with data for 4976 schizophrenia cases and 9012 controls from the Type-1 diabetes genetics consortium and Generation Scotland included for comparison. Exposure Standardised PRS, calculated using alleles with an association p-value threshold < 0.05 in the second Psychiatric Genomics Consortium genome-wide association study of schizophrenia, adjusted for the first 10 population principal components and genotyping-platform. Main outcome measure Multinomial logit models estimated PRS associations with BD stratified by (1) Research Diagnostic Criteria (RDC) BD subtypes (2) Lifetime occurrence of psychosis.(3) Lifetime mood-incongruent psychotic features and (4) ordinal logistic regression examined PRS associations across levels of mood-incongruence. Ratings were derived from the Schedule for Clinical Assessment in Neuropsychiatry interview (SCAN) and the Bipolar Affective Disorder Dimension Scale (BADDS). Results Across clinical phenotypes, there was an exposure-response gradient with the strongest PRS association for schizophrenia (RR=1.94, (95% C.I. 1.86, 2.01)), then schizoaffective BD (RR=1.37, (95% C.I. 1.22, 1.54)), BD I (RR= 1.30, (95% C.I. 1.24, 1.36)) and BD II (RR=1.04, (95% C.I. 0.97, 1.11)). Within BD cases, there was an effect gradient, indexed by the nature of psychosis, with prominent mood-incongruent psychotic features having the strongest association (RR=1.46, (95% C.I. 1.36, 1.57)), followed by mood-congruent psychosis (RR= 1.24, (95% C.I. 1.17, 1.33)) and lastly, BD cases with no history of psychosis (RR=1.09, (95% C.I. 1.04, 1.15)). Conclusion We show for the first time a polygenic-risk gradient, across schizophrenia and bipolar disorder, indexed by the occurrence and level of mood-incongruent psychotic symptoms