The neurochemically diverse intermedius nucleus of the medulla as a source of excitatory and inhibitory synaptic input to the nucleus tractus solitarii

Sensory afferent signals from neck muscles have been postulated to influence central cardiorespiratory control as components of postural reflexes, but neuronal pathways for this action have not been identified. The intermedius nucleus of the medulla (InM) is a target of neck muscle spindle afferents and is ideally located to influence such reflexes but is poorly investigated. To aid identification of the nucleus, we initially produced three-dimensional reconstructions of the InM in both mouse and rat. Neurochemical analysis including transgenic reporter mice expressing green fluorescent protein in GABA-synthesizing neurons, immunohistochemistry, and in situ hybridization revealed that the InM is neurochemically diverse, containing GABAegric and glutamatergic neurons with some degree of colocalization with parvalbumin, neuronal nitric oxide synthase, and calretinin. Projections from the InM to the nucleus tractus solitarius (NTS) were studied electrophysiologically in rat brainstem slices. Electrical stimulation of the NTS resulted in antidromically activated action potentials within InM neurons. In addition, electrical stimulation of the InM resulted in EPSPs that were mediated by excitatory amino acids and IPSPs mediated solely by GABA(A) receptors or by GABA(A) and glycine receptors. Chemical stimulation of the InM resulted in (1) a depolarization of NTS neurons that were blocked by NBQX (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonoamide) or kynurenic acid and (2) a hyperpolarization of NTS neurons that were blocked by bicuculline. Thus, the InM contains neurochemically diverse neurons and sends both excitatory and inhibitory projections to the NTS. These data provide a novel pathway that may underlie possible reflex changes in autonomic variables after neck muscle spindle afferent activation.

Immunopharmacology - antibodies for specific modulation of proteins involved in neuronal function

The application of antibodies to living neurones has the potential to modulate function of specific proteins by virtue of their high specificity. This specificity has proven effective in determining the involvement of many proteins in neuronal function where specific agonists and antagonists do not exist, e.g. ion channel subunits. We discuss studies where antibodies modulate functions of voltage gated sodium, voltage gated potassium, voltage gated calcium hyperpolarisation activated cyclic nucleotide (HCN gated) and transient receptor potential (TRP) channels. Ligand gated channels studied in this way include nicotinic acetylcholine receptors, purinoceptors and GABA receptors. Antibodies have also helped reveal the involvement of different intracellular proteins in neuronal functions including G-proteins as well as other proteins involved in trafficking, phosphoinositide signalling and neurotransmitter release. Some suggestions for control experiments are made to help validate the method. We conclude that antibodies can be extremely valuable in determining the functions of specific proteins in living neurones in neuroscience research.

Localization and function of the Kv3.1b subunit in the rat medulla oblongata: focus on the nucleus tractus solitarii

The voltage-gated potassium channel subunit Kv3.1 confers fast firing characteristics to neurones. Kv3.1b subunit immunoreactivity (Kv3.1b-IR) was widespread throughout the medulla oblongata, with labelled neurones in the gracile, cuneate and spinal trigeminal nuclei. In the nucleus of the solitary tract (NTS), Kv3.1b-IR neurones were predominantly located close to the tractus solitarius (TS) and could be GABAergic or glutamatergic. Ultrastructurally, Kv3.1b-IR was detected in NTS terminals, some of which were vagal afferents. Whole-cell current-clamp recordings from neurones near the TS revealed electrophysiological characteristics consistent with the presence of Kv3.1b subunits: short duration action potentials (4.2 +/- 1.4 ms) and high firing frequencies (68.9 +/- 5.3 Hz), both sensitive to application of TEA (0.5 mm) and 4-aminopyridine (4-AP; 30 mum). Intracellular dialysis of an anti-Kv3.1b antibody mimicked and occluded the effects of TEA and 4-AP in NTS and dorsal column nuclei neurones, but not in dorsal vagal nucleus or cerebellar Purkinje cells (which express other Kv3 subunits, but not Kv3.1b). Voltage-clamp recordings from outside-out patches from NTS neurones revealed an outward K(+) current with the basic characteristics of that carried by Kv3 channels. In NTS neurones, electrical stimulation of the TS evoked EPSPs and IPSPs, and TEA and 4-AP increased the average amplitude and decreased the paired pulse ratio, consistent with a presynaptic site of action. Synaptic inputs evoked by stimulation of a region lacking Kv3.1b-IR neurones were not affected, correlating the presence of Kv3.1b in the TS with the pharmacological effects.

Continuity of care for people with psychotic illness: its relationship to clinical and social functioning.

Background: The relationship between continuity of care and user characteristics or outcomes has rarely been explored. The ECHO study operationalized and tested a multi-axial definition of continuity of care, producing a seven-factor model used here. Aims: To assess the relationship between user characteristics and established components of continuity of care, and the impact of continuity on clinical and social functioning. Methods: The sample comprised 180 community mental health team users with psychotic disorders who were interviewed at three annual time-points, to assess their experiences of continuity of care and clinical and social functioning. Scores on seven continuity factors were tested for association with user-level variables. Results: Improvement in quality of life was associated with better Experience & Relationship continuity scores (better user-rated continuity and therapeutic relationship) and with lower Meeting Needs continuity factor scores. Higher Meeting Needs scores were associated with a decrease in symptoms. Conclusion: Continuity is a dynamic process, influenced significantly by care structures and organizational change.

Continuity of care for carers of people with severe mental illness: results of a longitudinal study

Introduction: Continuity of care has been demonstrated to be important for service users and carer groups have voiced major concerns over disruptions of care. We aimed to assess the experienced continuity of care in carers of patients with both psychotic and non-psychotic disorders and explore its association with carer characteristics and psychological well-being. Methods: Friends and relatives caring for two groups of service users in the care of community mental health teams (CMHTs), 69 with psychotic and 38 with non-psychotic disorders, were assessed annually at three and two time points, respectively. CONTINUES, a measure specifically designed to assess continuity of care for carers themselves, was utilized along with assessments of psychological well-being and caregiving. Results: One hundred and seven carers participated. They reported moderately low continuity of care. Only 22 had had a carer’s assessment and just under a third recorded psychological distress on the GHQ. For those caring for people with psychotic disorders, reported continuity was higher if the carer was male, employed, lived with the user and had had a carer’s assessment; for those caring for people with non-psychotic disorders, it was higher if the carer was from the service user’s immediate family, lived with them and had had a carer’s assessment. Conclusion: The vast majority of the carers had not had a carer’s assessment provided by the CMHT despite this being a clear national priority and being an intervention with obvious potential to increase carers’ reported low levels of continuity of care. Improving continuity of contact with carers may have an important part to play in the overall improvement of care in this patient group and deserves greater attention.

Conditionally unbiased estimation in phase II/III clinical trials with early stopping for futility

Seamless phase II/III clinical trials combine traditional phases II and III into a single trial that is conducted in two stages, with stage 1 used to answer phase II objectives such as treatment selection and stage 2 used for the confirmatory analysis, which is a phase III objective. Although seamless phase II/III clinical trials are efficient because the confirmatory analysis includes phase II data from stage 1, inference can pose statistical challenges. In this paper, we consider point estimation following seamless phase II/III clinical trials in which stage 1 is used to select the most effective experimental treatment and to decide if, compared with a control, the trial should stop at stage 1 for futility. If the trial is not stopped, then the phase III confirmatory part of the trial involves evaluation of the selected most effective experimental treatment and the control. We have developed two new estimators for the treatment difference between these two treatments with the aim of reducing bias conditional on the treatment selection made and on the fact that the trial continues to stage 2. We have demonstrated the properties of these estimators using simulations

Playing with history: negotiating subjectivity in contemporary lens based work

Contemporary artists exploring Jewish identity in the UK are caught between two exclusions, broadly speaking: an art community that that sees itself as ‘post –identity’ and a ‘black’ art scene that revolves around the organizations that emerged out of the Identity debates of the 1980s and 1990s, namely Iniva, Third Text, Autograph. These organizations and those debates, don’t usually include Jewish identity within their remit as Jewish artists are considered to be well represented in the British art scene and, in any case, white. Out of these assumptions, questions arise in relation to the position of Jews in Britain and what is at stake for an artist in exploring Jewish Identity in their work. There is considerable scholarship, relatively speaking on art and Jewish Identity in the US (such as Lisa Bloom; Norman Kleeblatt; Catherine Sousslouf), which inform the debates on visual culture and Jews. In this chapter, I will be drawing out some of the distinctions between the US and the UK debates within my analysis, building on my own writing over the last ten years as well as the work of Juliet Steyn, Jon Stratton and Griselda Pollock. In short, this chapter aims to explore the problematic of what Jewish Identity can offer the viewer as art; what place such art inhabits within a wider artistic context and how, if at all, it is received. There is a predominance of lens based work that explores Identity arising out of the provenance of feminist practices and the politics of documentary that will be important in the framing of the work. I do not aim to consider what constitutes a Jewish artist, that has been done elsewhere and is an inadequate and somewhat spurious conversation . I will also not be focusing on artists whose intention is to celebrate an unproblematised Jewishness (however that is constituted in any given work). Recent artworks and scholarship has in any case rendered the trumpeting of attachment to any singular identity anachronistic at best. I will focus on artists working in the UK who incorporate questions of Jewishness into a larger visual enquiry that build on Judith Butler’s notion of identity as process or performative as well as the more recent debates and artwork that consider the intersectionality of identifications that co-constitute provisional identities (Jones, Modood, Sara Ahmed, Braidotti/Nikki S Lee, Glenn Ligon). The case studies to think through these questions of identity, will be artworks by Susan Hiller, Doug Fishbone and Suzanne Triester. In thinking through works by these artists, I will also serve to contextualise them, situating them briefly within the history of the landmark exhibition in the UK, Rubies and Rebels and the work of Ruth Novaczek, Lily Markewitz, Oreet Ashery and myself.

The induction of mental and contact contamination

Background: Extreme fear of contamination within Obsessive Compulsive Disorder is traditionally conceptualised as a physical phenomenon. More recent research has supported the notion of ‘mental’ contamination, in which people feel contaminated in the absence of physical contact. The current research sought to determine whether feelings of contact and mental contamination could be induced within a non-clinical sample, whether the impact of mental and contact contamination was comparable in terms of associated feelings and behaviour and whether related psychopathology related to the impact of the tasks. Methods: Undergraduate students (n=60) completed OCD relevant measures and were randomly assigned to either a contact contamination condition (CC: moving a bucket of fake vomit) or a mental contamination condition (MC: thinking about a bucket of vomit). Results: Both manipulations induced feelings of contamination. Participants in the contact condition had significantly greater urges to wash than those in the mental condition. Neutralising behaviour did not differ across conditions. Conclusions: Feelings of contamination can be induced in the absence of physical contact and for those in the MC group, some aspects of OCD-relevant psychopathology were related to the impact of the manipulation. These findings have implications for the understanding and treatment of contamination-related fears in OCD.

Diagnosing the influence of diabatic processes on the explosive deepening of extratropical cyclones

A novel version of the classical surface pressure tendency equation (PTE) is applied to ERA-Interim reanalysis data to quantitatively assess the contribution of diabatic processes to the deepening of extratropical cyclones relative to effects of temperature advection and vertical motions. The five cyclone cases selected, Lothar and Martin in December 1999, Kyrill in January 2007, Klaus in January 2009, and Xynthia in February 2010, all showed explosive deepening and brought considerable damage to parts of Europe. For Xynthia, Klaus and Lothar diabatic processes contribute more to the observed surface pressure fall than horizontal temperature advection during their respective explosive deepening phases, while Kyrill and Martin appear to be more baroclinically driven storms. The powerful new diagnostic tool presented here can easily be applied to large numbers of cyclones and will help to better understand the role of diabatic processes in future changes in extratropical storminess.

Home, meaning and identity: learning from the English model of shared ownership

This article explores the problematic nature of the label “home ownership” through a case study of the English model of shared ownership, one of the methods used by the UK government to make home ownership affordable. Adopting a legal and socio-legal analysis, the article considers whether shared ownership is capable of fulfilling the aspirations households have for home ownership. To do so, the article considers the financial and nonfinancial meanings attached to home ownership and suggests that the core expectation lies in ownership of the value. The article demonstrates that the rights and responsibilities of shared owners are different in many respects from those of traditional home owners, including their rights as regards ownership of the value. By examining home ownership through the lens of shared ownership the article draws out lessons of broader significance to housing studies. In particular, it is argued that shared ownership shows the limitations of two dichotomies commonly used in housing discourse: that between private and social housing; and the classification of tenure between owner-occupiers and renters. The article concludes that a much more nuanced way of referring to home ownership is required, and that there is a need for a change of expectations amongst consumers as to what sharing ownership means.

The responsibility to record civilian casualties

The responsibility to record civilian casualties in both armed conflict and civil disturbances must be an integral element of the responsibility to protect, particularly in the application of the just cause principles. The first part of this article examines the threshold issue of the possibility of large-scale civilian casualties which triggers the international community’s responsibility to react. The reports recommending the responsibility to protect emphasise the need to establish the actuality or risk of ‘large scale’ loss of life which is not possible in the current context without a civilian casualty recording structure. The second part of the article outlines the international legal obligation to record civilian casualties based on international humanitarian law and international human rights law. Thirdly, the responsibility to protect and the legal obligation to record casualties are brought together within the framework of Ban Ki-moon’s reports on implementation of the Responsibility to Protect. The fourth and final part of the article reviews the situations in Sri Lanka and Syria. Both states represent egregious examples of governments hiding the existence of casualties, resulting in paralysis within the international community. These situations establish, beyond doubt, that the national obligation to record civilian casualties must be part and parcel of the responsibility to protect.

The international law implications of the Turkish/Kurdish conflict

This article considers the threaties and customs governing armed conflict in the context of the long standing insurgency in southeast Turkey. The first part of the article analyzes the existing treaty and customary law concerning the threshold of an armed conflict and concludes that the insurgency in Southeast Turkey existing since 1984 rises to the level of an armed conflict based on criteria identified both in treaty and customary international law. The next consideration is the classification of this conflict and this part concludes that this situation is a non-international armed conflict due to lack of involvement of forces of another country. Finally, this article considers international humanitarian law applicable to this non-international armed conflict and reveals that as a result of the monumental International Committee of the Red Cross customary humanitarian law study, particularly with respect to the law of targeting, that the rules applicable to international and non-international armed conflict have never been closer.

The Kurdish conflict: international humanitarian law and post-conflict mechanisms

This book is highly topical considering the recent resurgence of violence by the PKK, the incursions into Northern Iraq by the Turkish army and security forces and Turkey’s EU accession negotiations. Turkey has become an increasingly important player in Middle Eastern geopolitics. More than two decades of serious conflict in Turkey are proving to be a barrier to improved relations between Turkey and the EU. This book is the first study to address fully the legal and political dimensions of the conflict, and their impact on mechanisms for conflict resolution in the region, offering a scholarly exploration of a debate that is often politically and emotionally highly charged. Kerim Yildiz and Susan Breau look at the practical application of the law of armed conflicts to the ongoing situation in Turkey and Northern Iraq. The application of the law in this region also means addressing larger questions in international law, global politics and conflict resolution. Examples include belligerency in international law, whether the ‘war on terror’ has resulted in changes to the law of armed conflict and terrorism and conflict resolution. The Kurdish Conflict explores the practical possibilities of conflict resolution in the region, examining the political dynamics of the region, and suggesting where lessons can be drawn from other peace processes, such as in Northern Ireland. This book will be of great value to policy-makers, regional experts, and others interested in international humanitarian law and conflict resolution.