I can hear once more: The role of the Anaesthetic Nurse specialist in Cochlear implantation for people with long term deafness

This paper examines the role of the Anaesthetic Nuse Specialist(ANS) in the context of innovative cochlear implant surgery which restores hearing to those with long term deafness. The specific focus is patient centered care during the long surgery under local anaestha when the patient is awake.
It is crucial during this surgery that the patient remains still, relaxed and calm, the ANS has been particularly creative using communication cards and tablets to allow patients to write questions and the nurse to answer. The writers capture the unique moment when someone with long term hearing can hear, and the ensuing emotion from the patient and theatre team.

Protein deregulation associated with breast cancer metastasis

Breast cancer is one of the most prevalent malignancies worldwide. It consists of a group of tumor cells that have the ability to grow uncontrollably, overcome replicative senescence (tumor progression) and metastasize within the body. Metastases are processes that consist of an array of complex gene dysregulation events. Although these processes are still not fully understood, the dysregulation of a number of key proteins must take place if the tumor cells are to disseminate and metastasize. It is now widely accepted that future effective and innovative treatments of cancer metastasis will have to encompass all the major components of malignant transformation. For this reason, much research is now being carried out into the mechanisms that govern the malignant transformation processes. Recent research has identified key genes involved in the development of metastases, as well as their mechanisms of action. A detailed understanding of the encoded proteins and their interrelationship generates the possibility of developing novel therapeutic approaches. This review will focus on a select group of proteins, often deregulated in breast cancer metastasis, which have shown therapeutic promise, notably, EMT, E-cadherin, Osteopontin, PEA3, Transforming Growth Factor Beta (TGF-β) and Ran.

Cystic Fibrosis from Laboratory to Bedside: The Role of A20 in NF-κB-Mediated Inflammation

Cystic fibrosis (CF) is a lifelong, inflammatory multi-organ disease and the most common lethal, genetic condition in Caucasian populations, with a median survival rate of 41.5 years. Pulmonary disease, characterized by infective exacerbations, bronchiectasis and increasing airway insufficiency is the most serious manifestation of this disease process, currently responsible for over 80% of CF deaths. Chronic dysregulation of the innate immune and host inflammatory response has been proposed as a mechanism central to this genetic condition, primarily driven by the nuclear factor κB (NF-κB) pathway. Chronic activation of this transcription factor complex leads to the production of pro-inflammatory cytokines and mediators such as IL-6, IL-8 and TNF-α. A20 has been described as a central and inducible negative regulator of NF-κB. This intracellular molecule negatively regulates NF-κB-driven pro-inflammatory signalling upon toll-like receptor activation at the level of TRAF6 activation. Silencing of A20 increases cellular levels of p65 and induces a pro-inflammatory state. We have previously shown that A20 expression positively correlates with lung function (FEV1%) in CF. Despite improvement in survival rates in recent years, advancements in available therapies have been incremental. We demonstrate that the experimental use of naturally occurring plant diterpenes such as gibberellin on lipopolysaccharide-stimulated cell lines reduces IL-8 release in an A20-dependent manner. We discuss how the use of a novel bio-informatics gene expression connectivity-mapping technique to identify small molecule compounds that similarly mimic the action of A20 may lead to the development of new therapeutic approaches capable of reducing chronic airway inflammation in CF. 

Parainflammation, chronic inflammation, and age-related macular degeneration

Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune-privileged tissue as a result of its unique anatomic and physiologic properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate-immune system, particularly microglia and the complement system, undergoes low levels of activation (parainflammation). In many cases, this parainflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration, this parainflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal parainflammation include genetic predisposition, environmental risk factors, and old age. Dysregulated parainflammation (chronic inflammation) in age-related macular degeneration damages the blood retina barrier, resulting in the breach of retinal-immune privilege, leading to the development of retinal lesions. This review discusses the basic principles of retinal innate-immune responses to endogenous chronic insults in normal aging and in age-related macular degeneration and explores the difference between beneficial parainflammation and the detrimental chronic inflammation in the context of age-related macular degeneration.

Innate Lymphoid Cells are the Predominant Source of Interleukin-17A During the Early Pathogenesis of Acute Respiratory Distress Syndrome

Rationale: IL-17A is purported to help drive early pathogenesis in acute respiratory distress syndrome (ARDS) by enhancing neutrophil recruitment. Whilst IL-17A is the archetypal cytokine of T helper (Th)17 cells, it is produced by a number of lymphocytes, the source during ARDS being unknown.

Objectives: To identify the cellular source and the role of IL17A in the early phase of lung injury

Methods: Lung injury was induced in WT (C57BL/6) and IL-17 KO mice with aerosolised LPS (100 µg) or Pseudomonas aeruginosa infection. Detailed phenotyping of the cells expressing RORγt, the transcriptional regulator of IL-17 production, in the mouse lung at 24 hours was carried out by flow cytometry.

Measurement and Main Results: A 100-fold reduction in neutrophil infiltration was observed in the lungs of the IL-17A KO compared to wild type (WT) mice. The majority of RORγt+ cells in the mouse lung were the recently identified type 3 innate lymphoid cells (ILC3). Detailed characterisation revealed these pulmonary ILC3s (pILC3s) to be discrete from those described in the gut. The critical role of these cells was verified by inducing injury in Rag2 KO mice which lack T cells but retain ILCs. No amelioration of pathology was observed in the Rag2 KO mice.

Conclusions: IL-17 is rapidly produced during lung injury and significantly contributes to early immunopathogenesis. This is orchestrated largely by a distinct population of pILC3 cells. Modulation of pILC3s’ activity may potentiate early control of the inflammatory dysregulation seen in ARDS, opening up new therapeutic targets.

Emotions & social change in Ireland:Exploring habitus shift in liquid modernity

Drawing on insights from a range of disciplines, including philosophy, psychology, history, politics, but particularly sociology and sociological theory, this thesis explores the relationship between emotions and social change in late or 'liquid' modernity. It deploys the Republic of Ireland in the twentieth century as a case study. It argues that the Irish case in an ideal site for this research given the speed and scale of changes that have occurred there, particularly since the 1950's. The primary research question guiding the study is: What has been the effect of 'social change' in Ireland on the emotional lives of Irish people? The thesis is structured in three parts. Part one (chapters one to three) is primarily theoretical. It aims to develop a distinctive theoretical framework, process-relational realism, and argues that three concepts, properly treated, are central to answering the research question. These are emotion, power and (emotional) habitus. Part two is a bridging chapter, in which the empirical portion of the study, its design and method, are outlined. This study is based on a series of qualitative life-history interviews conducted using the Biographical Narrative Research Method. Part three is primarily empirical. The first chapter critically explores Bauman's concept of liquid modernity in relation to the Irish case and offers a short social history of the Irish twentieth century, which focuses on emotions and power. The second deploys two (ideal-type) interview cases to support the argument that Ireland experienced a habitus shift, from a relatively homogeneous to a heterogeneous habitus, and a corresponding shift from a relatively repressive emotional regime to a more expressive one, with significant effects on the emotional habitus. The final chapter takes a broader view of these changes, suggests that social change has been ambivalent, and outlines a new typology of emotional pathologies that the study suggests are characteristic of contemporary emotional life.

Emotional response to images of wind turbines: A psychophysiological study of their visual impact on the landscape

Social acceptance for wind turbines is variable, providing a challenge to the implementation of this energy source. Psychological research could contribute to the science of climate change. Here we focus on the emotional responses to the visual impact of wind turbines on the landscape, a factor which dominates attitudes towards this technology. Participants in the laboratory viewed images of turbines and other constructions (churches, pylons and power-plants) against rural scenes, and provided psychophysiological and self-report measures of their emotional reactions. We hypothesised that the emotional response to wind turbines would be more negative and intense than to control objects, and that this difference would be accentuated for turbine opponents. As predicted, the psychophysiological response to turbines was stronger than the response to churches, but did not differ from that of other industrial constructions. In contrast with predictions, turbines were rated as less aversive and more calming compared with other industrial constructions, and equivalent to churches. Supporters and non-supporters did not differ significantly from each other. We discuss how a methodology using photo manipulations and emotional self-assessments can help estimate the emotional reaction to the visual impact on the landscape at the planning stage for new wind turbine applications.

Rent: apartment blocks and their uses

In 1974, pursuing his interest in the infra-ordinary – ‘the banal, the quotidian, the obvious, the common, the ordinary, the back-ground noise, the habitual’ – Georges Perec wrote about an idea for a novel:
‘I imagine a Parisian apartment building whose façade has been removed … so that all the rooms in the front, from the ground floor up to the attics, are instantly and simultaneously visible’.
In Life A User’s Manual (1978) the consummation of this precis, patterns of existence are measured within architectural space with an archaeological sensibility that sifts through narrative and décor, structure and history, services and emotion, the personal and the system, ascribing commensurate value to each.
Apartment comes from the Italian appartare meaning ‘to separate’. The space of the boundary between activities is reduced to a series of intimately thin lines: the depth of a floor, a party wall, a window, the convex peep-hole in a door, or the façade that Perec seeks to render invisible. The apartness of the apartment is accelerated when aligned with short-term tenancies. Here Perec’s interweaving of personal histories over time using the structure of the block, gives way to convivialities of detachment: inhabitants are temporary, their personalities anonymous, their activities unknown or overlooked.
Borrowing methods from Perec, to move somewhere between conjecture, analysis and other documentation and tracing relationships between form, structure, materiality, technology, organisation, tenure and narrative use, this paper interrogates the late twentieth-century speculative apartment block in Britain and Ireland arguing that its speculative and commodified purpose allows a series of lives that are often less than ordinary to inhabit its spaces.
Henri Lefebvre described the emergence of an ‘abstract space’ under capitalism in terms which can be applied to the apartment building: the division of space into freely alienable privatised parcels which can be exchanged. Vertical distributions of class and other new, contiguous social and spatial relationships are couched within a paradox: the building which allows such proximities is also a conductor of division. Apartment comes from the Italian appartare meaning ‘to separate’. The space of the boundary between activities is reduced to a series of intimately thin lines: the depth of a floor, a party wall, a window, the convex peep-hole in a door, or the façade that Perec seeks to render invisible. The apartness of the apartment is accelerated when aligned with short-term tenancies. Here Perec’s interweaving of personal histories over time using the structure of the block, gives way to convivialities of detachment: inhabitants are temporary, their personalities anonymous, their activities unknown or overlooked.

Ischemic A/D transition of mitochondrial complex I and its role in ROS generation

Mitochondrial complex I (NADH:ubiquinone oxidoreductase) is a key enzyme in cellular energy metabolism and provides approximately 40% of the proton-motive force that is utilized during mitochondrial ATP production. The dysregulation of complex I function – either genetically, pharmacologically, or metabolically induced – has severe pathophysiological consequences that often involve an imbalance in the production of reactive oxygen species (ROS). Slow transition of the active (A) enzyme to the deactive, dormant (D) form takes place during ischemia in metabolically active organs such as the heart and brain. The reactivation of complex I occurs upon reoxygenation of ischemic tissue, a process that is usually accompanied by an increase in cellular ROS production. Complex I in the D-form serves as a protective mechanism preventing the oxidative burst upon reperfusion. Conversely, however, the D-form is more vulnerable to oxidative/nitrosative damage. Understanding the so-called active/deactive (A/D) transition may contribute to the development of new therapeutic interventions for conditions like stroke, cardiac infarction, and other ischemia-associated pathologies. In this review, we summarize current knowledge on the mechanism of A/D transition of mitochondrial complex I considering recently available structural data and site-specific labeling experiments. In addition, this review discusses in detail the impact of the A/D transition on ROS production by complex I and the S-nitrosation of a critical cysteine residue of subunit ND3 as a strategy to prevent oxidative damage and tissue damage during ischemia–reperfusion injury.

Property and Emotions

Relatively little has been written on the connection between property and emotions from a legal perspective, despite the centrality of property in everyday life and the complex relationships that exist between owners and their property. Scholars working in other disciplines have analyzed these links, identifying ‘proprietary’ emotions and corresponding emotional traits. However, little has been mapped onto the field of law. This paper looks at key emotions surrounding property as identified in psychological and, to a lesser extent, sociological literature. After mapping these onto selected areas of property law, it posits the need for a deeper and more collective field of inquiry.

Lateral bias and temperament in the domestic cat (Felis silvestris)

Research points to a relationship between lateralization and emotional functioning in humans and many species of animal. The present study explored the association between paw preferences and emotional functioning, specifically temperament, in a species thus far overlooked in this area, the domestic cat. Thirty left-pawed, 30 right-pawed, and 30 ambilateral pet cats were recruited following an assessment of their paw preferences using a food-reaching challenge. The animals’ temperament was subsequently assessed using the Feline Temperament Profile (FTP). Cats’ owners also completed a purpose-designed cat temperament (CAT) scale. Analysis revealed a significant relationship between lateral bias and FTP and CAT scale scores. Ambilateral cats had lower positive (FTP+) scores, and were perceived as less affectionate, obedient, friendly, and more aggressive, than left or right-pawed animals. Left and right pawed cats differed significantly on 1 trait on the CAT scale, namely playfulness. The strength of the cats’ paw preferences was related to the animals’ FTP and CAT scores. Cats with a greater strength of paw preference had higher FTP + scores than those with a weaker strength of paw preference. Animals with stronger paw preferences were perceived as more confident, affectionate, active, and friendly than those with weaker paw preferences. Results suggest that motor laterality in the cat is strongly related to temperament and that the presence or absence of lateralization has greater implications for the expression of emotion in this species than the direction of the lateralized bias.

The Development of Regret and Relief About the Outcomes of Risky Decisions

Although a number of studies have examined the developmental emergence of counterfactual emotions of regret and relief, none of these have used tasks that resemble those used with adolescents and adults, which typically involve risky decision making. We examined the development of the counterfactual emotions of regret and relief in two experiments using a task in which children chose between one of two gambles that varied in risk. In regret trials they always received the best prize from that gamble but were then shown that they would have obtained a better prize had they chosen the alternative gamble, whereas in relief trials the other prize was worse. We compared two methods of measuring regret and relief based on children’s reported emotion on discovering the outcome of the alternative gamble, one in which children judged whether they now felt the same, happier, or sadder on seeing the other prize and one in which children made emotion ratings on a 7-point scale after the other prize was revealed. On both these methods, we found that 6- to 7-year-olds’ and 8- to 9-year-olds’ emotions varied appropriately depending on whether the alternative outcome was better or worse than the prize they had actually obtained, although the former method was more sensitive. Our findings indicate that by at least 6-7 years, children experience the same sorts of counterfactual emotions as adults in risky decision making tasks, and also suggest that such emotions are best measured by asking children to make comparative emotion judgments.

Persistent endothelial activation and inflammation after Plasmodium falciparum Infection in Malawian children

Endothelial dysregulation is central to the pathogenesis of acute Plasmodium falciparum infection. It has been assumed that this dysregulation resolves rapidly after treatment, but this return to normality has been neither demonstrated nor quantified. We therefore measured a panel of plasma endothelial markers acutely and in convalescence in Malawian children with uncomplicated or cerebral malaria. Evidence of persistent endothelial activation and inflammation, indicated by increased plasma levels of soluble intracellular adhesion molecule 1, angiopoetin 2, and C-reactive protein, were observed at 1 month follow-up visits. These vascular changes may represent a previously unrecognized contributor to ongoing malaria-associated morbidity and mortality.