Localization of NG2 immunoreactive neuroglia cells in the rat locus coeruleus and their plasticity in response to stress

The locus coeruleus (LC) nucleus modulates adaptive behavioural responses to stress and dysregulation of LC neuronal activity is implicated in stress-induced mental illnesses. The LC is composed primarily of noradrenergic neurons together with various glial populations. A neuroglia cell-type largely unexplored within the LC is the NG2 cell. NG2 cells serve primarily as oligodendrocyte precursor cells throughout the brain. However, some NG2 cells are in synaptic contact with neurons suggesting a role in information processing. The aim of this study was to neurochemically and anatomically characterise NG2 cells within the rat LC. Furthermore, since NG2 cells have been shown to proliferate in response to traumatic brain injury, we investigated whether such NG2 cells plasticity also occurs in response to emotive insults such as stress. Immunohistochemistry and confocal microscopy revealed that NG2 cells were enriched within the pontine region occupied by the LC. Close inspection revealed that a sub-population of NG2 cells were located within unique indentations of LC noradrenergic somata and were immunoreactive for the neuronal marker NeuN whilst NG2 cell processes formed close appositions with clusters immunoreactive for the inhibitory synaptic marker proteins gephyrin and the GABA-A receptor alpha3-subunit, on noradrenergic dendrites. In addition, LC NG2 cell processes were decorated with vesicular glutamate transporter 2 immunoreactive puncta. Finally, ten days of repeated restraint stress significantly increased the density of NG2 cells within the LC. The study demonstrates that NG2 IR cells are integral components of the LC cellular network and they exhibit plasticity as a result of emotive challenges

‘Standing by’: disability hate crime and the police in England

This article discusses the Don’t Stand By: Hate Crime Research Report (DSB) (Mencap, 2011), which documents failings in policing practices related to reporting and responding to disability hate crime. Such failings, we argue, constitute not so much direct discrimination but acts of ‘normalcy’. Normalcy is the process whereby taken for granted ideas about what is normal become naturalised; in this respect being non-disabled is seen as normal. Acts of normalcy, whilst less tangible, are by no means less violent or harmful than acts of ‘real discrimination’ or ‘real violence’ (Goodley and Rumswick-Cole, 2011). Systemic and cultural normalcy within the police is not new, as can be seen in the case of Stephen Lawrence

Service user suicides and coroner's inquests

This is an Accepted Manuscript of an article published by Taylor & Francis in Criminal Justice Matters on 22nd May 2013, available online: DOI:10.1080/09627251.2013.805375The expansion of victimology in the 1980s produced a more nuanced understanding of victims and victimisation. Yet responses of government, criminal justice agencies, media and general public to victims are predictably and predominantly focused on victims of ‘conventional crime’. We challenge this perspective, thus widening the victimological lens. We discuss the impact of self-inflicted deaths and subsequent coronial inquests on practitioners working on behalf of the state

Novel in-situ real-time line scan optical monitoring of wear and surface damage initiation in a laboratory twin disc test

A new optical monitoring system has been developed to photograph in-situ in real time the initiation of damage on the running surface of a rail steel twin-disc sample undergoing wear testing. The line-scan camera system has been demonstrated on the Sheffield University ROlling Sliding 2 (SUROS2) twin-disc machine. The results show the system can continuously track the development of wear flakes, with wear flake initiation and stabilisation of wear flake size observed without test interruption for the first time. Image analysis to quantify the total wear flake shadow pixel count showed a good correlation with the mass loss results, indicating the potential for the optical data to quantify rail steel wear without interruption to testing. Furthermore, in a water-lubricated test the new system enables observation of rolling contact fatigue (RCF) crack initiation through a water layer present on the specimens, without requiring test interruption. The improving knowledge of the wear and RCF performance of rail steels available from the new observation method can help improve understanding of steel performance and support to the selection of rail steel grades according to their performance

Nano and micro-indentation driven characterisation of asperity and bulk plasticity at the surface of modern premium rail steels

The plastic deformation behaviour of rail steels due to cyclic rail-wheel contacts is important to understand due to its connection to wear and rolling contact fatigue (RCF) damage initiation in service. Simulation models such as the ‘Layer’ and ‘Brick’ model have previously been developed to estimate the accumulation of plastic damage in a rail steel; however, the data available to drive these models is currently sparse, with limited applicability to modern rail steel grades. This paper presents the research examining the shear stress-strain curve relationships of rail steels derived from plastic shear strain and shear yield stress data collected from twin-disc test samples. A combination of microhardness and nanohardness testing was used to derive the shear yield stress data, whereas the plastic shear strain was acquired from optical microscopy. Six different conditions were investigated for this research for the purpose of examining how shear stress-strain curve relationships compared between the standard R260 and the premium HP335 and R350HT rail steels and how this compares to wear damage data. The influence of the maximum Hertzian contact pressure on the shear stress-strain curve relationships of R260 between 600 and 1500 MPa contact pressure was also investigated. The wear rate results derived from the mass loss in interrupted twin-disc tests showed HP335 wearing the least, followed by R350HT and then R260 for 1500 MPa, dry contact conditions. However, the highest shear yield stress achieved was for R350HT, then HP335, and R260. The results show that the shear stress-strain curve relationships by themselves are insufficient to determine rail steel wear performance in a laboratory environment. The shear stress-strain curve relationships for R260 collected under different contact pressures showed the results are near independent of the contact pressure within the range explored

Decompressive craniectomy following traumatic brain injury: developing the evidence base.

In the context of traumatic brain injury (TBI), decompressive craniectomy (DC) is used as part of tiered therapeutic protocols for patients with intracranial hypertension (secondary or protocol-driven DC). In addition, the bone flap can be left out when evacuating a mass lesion, usually an acute subdural haematoma (ASDH), in the acute phase (primary DC). Even though, the principle of "opening the skull" in order to control brain oedema and raised intracranial pressure has been practised since the beginning of the 20th century, the last 20 years have been marked by efforts to develop the evidence base with the conduct of randomised trials. This article discusses the merits and challenges of this approach and provides an overview of randomised trials of DC following TBI. An update on the RESCUEicp study, a randomised trial of DC versus advanced medical management (including barbiturates) for severe and refractory post-traumatic intracranial hypertension is provided. In addition, the rationale for the RESCUE-ASDH study, the first randomised trial of primary DC versus craniotomy for adult head-injured patients with an ASDH, is presented.The RESCUEicp study is funded by the Efficacy and Mechanism Evaluation (EME) Programme, an MRC and National Institute for Health Research (NIHR) partnership (project number 09/800/16). The views expressed in this publication are those of the authors and not necessarily those of the MRC, NHS, NIHR or the Department of Health. The RESCUE-ASDH study is funded by the NIHR Health Technology Assessment programme (project number 12/35/57). The views and opinions expressed herein are those of the authors and do not necessarily reflect those of the Health Technology Assessment programme, NIHR, NHS or the Department of Health.This is the final version of the article. It first appeared from Taylor & Francis via https://doi.org/10.3109/02688697.2016.115965

GABA Receptors and the Pharmacology of Sleep

Current GABAergic sleep-promoting medications were developed pragmatically, without making use of the immense diversity of GABAA receptors. Pharmacogenetic experiments are leading to an understanding of the circuit mechanisms in the hypothalamus by which zolpidem and similar compounds induce sleep at α2βγ2-type GABAA receptors. Drugs acting at more selective receptor types, for example, at receptors containing the α2 and/or α3 subunits expressed in hypothalamic and brain stem areas, could in principle be useful as hypnotics/anxiolytics. A highly promising sleep-promoting drug, gaboxadol, which activates αβδ-type receptors failed in clinical trials. Thus, for the time being, drugs such as zolpidem, which work as positive allosteric modulators at GABAA receptors, continue to be some of the most effective compounds to treat primary insomnia

Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension.

BACKGROUND: The effect of decompressive craniectomy on clinical outcomes in patients with refractory traumatic intracranial hypertension remains unclear. METHODS: From 2004 through 2014, we randomly assigned 408 patients, 10 to 65 years of age, with traumatic brain injury and refractory elevated intracranial pressure (>25 mm Hg) to undergo decompressive craniectomy or receive ongoing medical care. The primary outcome was the rating on the Extended Glasgow Outcome Scale (GOS-E) (an 8-point scale, ranging from death to "upper good recovery" [no injury-related problems]) at 6 months. The primary-outcome measure was analyzed with an ordinal method based on the proportional-odds model. If the model was rejected, that would indicate a significant difference in the GOS-E distribution, and results would be reported descriptively. RESULTS: The GOS-E distribution differed between the two groups (P<0.001). The proportional-odds assumption was rejected, and therefore results are reported descriptively. At 6 months, the GOS-E distributions were as follows: death, 26.9% among 201 patients in the surgical group versus 48.9% among 188 patients in the medical group; vegetative state, 8.5% versus 2.1%; lower severe disability (dependent on others for care), 21.9% versus 14.4%; upper severe disability (independent at home), 15.4% versus 8.0%; moderate disability, 23.4% versus 19.7%; and good recovery, 4.0% versus 6.9%. At 12 months, the GOS-E distributions were as follows: death, 30.4% among 194 surgical patients versus 52.0% among 179 medical patients; vegetative state, 6.2% versus 1.7%; lower severe disability, 18.0% versus 14.0%; upper severe disability, 13.4% versus 3.9%; moderate disability, 22.2% versus 20.1%; and good recovery, 9.8% versus 8.4%. Surgical patients had fewer hours than medical patients with intracranial pressure above 25 mm Hg after randomization (median, 5.0 vs. 17.0 hours; P<0.001) but had a higher rate of adverse events (16.3% vs. 9.2%, P=0.03). CONCLUSIONS: At 6 months, decompressive craniectomy in patients with traumatic brain injury and refractory intracranial hypertension resulted in lower mortality and higher rates of vegetative state, lower severe disability, and upper severe disability than medical care. The rates of moderate disability and good recovery were similar in the two groups. (Funded by the Medical Research Council and others; RESCUEicp Current Controlled Trials number, ISRCTN66202560 .).Supported by the Medical Research Council (MRC) and managed by the National Institute for Health Research (NIHR) on behalf of the MRC–NIHR partnership (grant no. 09/800/16), and by the NIHR Cambridge Biomedical Research Centre, the Academy of Medical Sciences and Health Foundation (Senior Fellowship, to Dr. Hutchinson), and the Evelyn Trust. Dr. Hutchinson is supported by a Research Professorship from the NIHR, the NIHR Cambridge Biomedical Research Centre, a European Union Seventh Framework Program grant (CENTER-TBI; grant no. 602150), and the Royal College of Surgeons of England; Dr. Kolias, by a Royal College of Surgeons of England Research Fellowship and a Sackler Studentship; Dr. Pickard, by the NIHR Brain Injury Healthcare Technology Co-operative and a Senior Investigator award from the NIHR; and Dr. Menon, by a Senior Investigator award from the NIHR and a European Union Seventh Framework Program grant (CENTER-TBI; grant no. 602150). The University of Cambridge and Cambridge University Hospitals NHS Foundation Trust were the trial sponsors.This is the author accepted manuscript. The final version is available from the Massachusetts Medical Society via http://dx.doi.org/10.1056/NEJMoa160521

The Coroner’s inquest and visceral reactions: Considering the impact of self-inflicted deaths on the health and social care professional

This book chapter is not available through ChesterRep.This book chapter presents a discussion of the potential impact of participation in the Coroner’s Inquest for health and social care professionals

A companion to criminal justice, mental health and risk

This edited book is not available through ChesterRep.Within the domains of criminal justice and mental health care, critical debate concerning ‘care’ versus ‘control’ and ‘therapy’ versus ‘security’ is now commonplace. Indeed, the ‘hybridisation’ of these areas is now a familiar theme. This unique and topical text provides an array of expert analyses from key contributors in the field that explore the interface between criminal justice and mental health. Using concise yet robust definitions of key terms and concepts, it consolidates scholarly analysis of theory, policy and practice. Readers are provided with practical debates, in addition to the theoretical and ideological concerns surrounding the risk assessment, treatment, control and risk management in a cross-disciplinary context. Included in this book is recommended further reading and an index of legislation, making it an ideal resource for students at undergraduate and postgraduate level, together with researchers and practitioners in the field