Detecting the myth : an application of C. G. Jung's analytical psychology to film analysis

This thesis applies the analytical psychology of C. G. Jung to the study of films. The thesis is in three parts. Part One forms an introduction to the theory of analytical psychology and makes the initial links to film theory. Part Two involves the development of a model for systematically applying the theory and Part Three is a detailed analysis of one film. Part One: In Chapter One Jung's theories about conscious behaviour are explored, some initial points of contact are made with film analysis, and a variety of films are used to illustrate the relevance of the theory. Chapter Two finds areas of correspondance between Jung's theories of the unconscious and film theory. This is a bridging of what had previously been regarded as separate critical traditions. Chapter Three is a detailed analysis of Tightrope (Dir. R. Tuggle, Warner Brothers, 1984) which demonstrates the applicability of analytical psychology n the analysis of films. Part Two: Chapter Four presents more theory about the nature of archetypes, and from this a model is derived. This model enables the central tenets of analytical psychology to be used for the analysis of films. This is demonstrated in Chapter Five which is an analysis of the detective film Blade Runner (Dir. R. Scott, Columbia, 1982). Chapter Six explores the function of the symbol in film, especially how it relates to the development of the narrative and to the psychological growth of the film's central characters. Chapter Seven is the last of the theoretical chapters and indicates how the individuation process can be applied to films. The figures of the shadow and the femme fatale are regarded as having a particular generic and cultural importance. Part Three: The remaining chapters are a detailed examination of Trancers (Dir. C. Band, Lexyen Productions, 1984), in which the model established in Chapter Four is used to facilitate the analysis of the film. This reveals that beneath the visual and narrative surface of the film there exists a series of mythological and psychological structures. Ultimately the film is regarded as an expression of collective latent unconscious psychological needs

Improving Seaglider Efficiency: An Analysis of Wing Shapes, Hull Morphologies, and Propulsion Methods

Autonomous underwater gliders are a family of autonomous underwater vehicles used for long-term observation of oceanic environments. These gliders leverage changes in buoyancy and the resulting vertical motion, to generate forward locomotion via hydrodynamic surfaces. In order to function for extended periods, these systems operate in a low-speed, low-drag regime. This research examines factors impacting the operational efficiencies of gliders, including morphological changes, configuration changes, and propulsion. An interesting question arises when considering the operational efficiencies of conventionally propelled systems at the operating speeds typical of gliders. Can a conventional propulsion system match the efficiency of an underwater glider buoyancy engine? A first-principles, energy-based approach to glider operations was derived and verified using real world data. The energy usage for buoyancy driven propulsion was then compared to conventional propulsion types. The results from these calculations indicate that a conventionally propelled autonomous underwater vehicle can compete with and in some cases outperform a buoyancy driven system given the proper propulsive efficiency

Multiple roles for NaV1.9 in visceral afferent activation by noxious mechanical and inflammatory stimuli.

PhDChronic visceral pain affects millions of individuals worldwide, remains poorly understood, and current therapeutics are constrained by undesirable adverse events. Inflammation and distension of visceral organs are common causes of pain, suggesting drugs targeting these signalling pathways may be efficacious visceral treatments. The voltage-gated sodium channel subtype 1.9 (NaV1.9) has been strongly associated with the development of inflammatory pain by rodent studies and more recently, by the identification of channelopathies in man. The aim of these studies was to investigate the role of NaV1.9 in visceral afferent signalling in the gut. Data from this thesis demonstrates that NaV1.9 is expressed by approximately half of gut-projecting rodent dorsal root ganglia sensory neurons. Consistent with significant expression in visceral afferents, NaV1.9 is required for normal mechanosensation, and for the direct excitation and mechanical hypersensitisation of mouse colonic afferents by inflammatory mediators applied as an inflammatory soup (bradykinin, ATP, histamine, PGE2, and 5HT) or derived from man (as inflammatory bowel disease tissue supernatants). Additionally, the importance of P2Y receptor activation in both rodent and human gut to algogenic purinergic signalling was demonstrated. Collectively, these results demonstrate that NaV1.9, is required for persistence of responses to intense mechanical stimulation, contributes to inflammatory mechanical hypersensitivity, and is essential for activation by noxious inflammatory mediators, including those from diseased human bowel. These findings suggest that NaV1.9 represents a high-value target for development of visceral analgesics.Biotechnology and Biological Sciences Research Council Neusentis Pfizer, for fundi

Human visceral nociception: findings from translational studies in human tissue.

Peripheral sensitization of nociceptors during disease has long been recognized as a leading cause of inflammatory pain. However, a growing body of data generated over the last decade has led to the increased understanding that peripheral sensitization is also an important mechanism driving abdominal pain in highly prevalent functional bowel disorders, in particular, irritable bowel syndrome (IBS). As such, the development of drugs that target pain-sensing nerves innervating the bowel has the potential to be a successful analgesic strategy for the treatment of abdominal pain in both organic and functional gastrointestinal diseases. Despite the success of recent peripherally restricted approaches for the treatment of IBS, not all drugs that have shown efficacy in animal models of visceral pain have reduced pain end points in clinical trials of IBS patients, suggesting innate differences in the mechanisms of pain processing between rodents and humans and, in particular, how we model disease states. To address this gap in our understanding of peripheral nociception from the viscera and the body in general, several groups have developed experimental systems to study nociception in isolated human tissue and neurons, the findings of which we discuss in this review. Studies of human tissue identify a repertoire of human primary afferent subtypes comparable to rodent models including a nociceptor population, the targeting of which will shape future analgesic development efforts. Detailed mechanistic studies in human sensory neurons combined with unbiased RNA-sequencing approaches have revealed fundamental differences in not only receptor/channel expression but also peripheral pain pathways.Non

Acute inflammation sensitizes knee-innervating sensory neurons and decreases mouse digging behavior in a TRPV1-dependent manner.

Ongoing, spontaneous pain is characteristic of inflammatory joint pain and reduces an individual's quality of life. To understand the neural basis of inflammatory joint pain, we made a unilateral knee injection of complete Freund's adjuvant (CFA) in mice, which reduced their natural digging behavior. We hypothesized that sensitization of knee-innervating dorsal root ganglion (DRG) neurons underlies this altered behavior. To test this hypothesis, we performed electrophysiological recordings on retrograde labeled knee-innervating primary DRG neuron cultures and measured their responses to a number of electrical and chemical stimuli. We found that 24-h after CFA-induced knee inflammation, knee neurons show a decreased action potential generation threshold, as well as increased GABA and capsaicin sensitivity, but have unaltered acid sensitivity. The inflammation-induced sensitization of knee neurons persisted for 24-h in culture, but was not observed after 48-h in culture. Through immunohistochemistry, we showed that the increased knee neuron capsaicin sensitivity correlated with enhanced expression of the capsaicin receptor, transient receptor potential vanilloid 1 (TRPV1) in knee-innervating neurons of the CFA-injected side. We also observed an increase in the co-expression of TRPV1 with tropomyosin receptor kinase A (TrkA), which is the receptor for nerve growth factor (NGF), suggesting that NGF partially induces the increased TRPV1 expression. Lastly, we found that systemic administration of the TRPV1 antagonist, A-425619, reversed the decrease in digging behavior induced by CFA injection, further confirming the role of TRPV1, expressed by knee neurons, in acute inflammatory joint pain.S.C. was supported by a Gates Cambridge Trust scholarship and L.A.P. was supported by the University of Cambridge BBSRC Doctoral Training Programme (BB/M011194/1)

Gut Reaction: The Impact of a Film on Public Understanding of Gastrointestinal Conditions

Chronic gastrointestinal (GI) tract conditions, such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are common conditions associated with disordered bowel movements and significant pain. However, discussion of bowel habits is often regarded as taboo and public understanding of what exactly IBD, IBS and related conditions are, and how they impact the lives of those individuals with such conditions is poorly understood. To provide a platform for enhancing public engagement of chronic bowel conditions, a short film was made (Gut Reaction) examining the lives of four individuals with different bowel conditions and what scientists and clinicians are doing to help alleviate the pain experienced by such individuals. The study design involved screening the film at a science festival where a pre- and post-film survey was conducted alongside follow up semi-structured interviews with a small subset of those who had expressed willingness to engage in such an interview. Although films have been used for public engagement and health campaigns, there is a lack of a robust evaluation of such methods. As such, there is no knowledge of impacts and outcomes, jeopardising funding of such projects (Haenssgen, 2019). Overall, the pre- and post-film surveys demonstrated that the film had increased the attendees’ understanding of chronic bowel conditions, how they are treated, what research is on-going and the likelihood of discussing bowel conditions with friends and family. The follow-up interviews were analysed through the constant comparative coding process. The analysis revealed that participants have a strong belief that bowel conditions need to be part of normal conversations, and the understanding of such conditions, and the people who experience them, needs to be improved by society. Our participants hold that this is crucial for people who experience from such conditions, not least to be able to access help sooner and suffer less. Finally, our participants discussed two strategies to achieve this societal openness and tackle the sense of shame around these issues: one involving role models and the other the media. In summary, Gut Reaction appeared to have met its objectives of improving the viewers’ awareness and understanding of chronic bowel conditions, as well as removing some of the stigma and taboo that surround discussions about these conditions. Consequently, the implications of this study are that making short films around taboo topics are an appropriate method to improve awareness and societal understanding of such topics.</jats:p

Acid and inflammatory sensitisation of naked mole-rat colonic afferent nerves.

Acid sensing in the gastrointestinal tract is required for gut homeostasis and the detection of tissue acidosis caused by ischaemia, inflammation and infection. In the colorectum, activation of colonic afferents by low pH contributes to visceral hypersensitivity and abdominal pain in human disease including during inflammatory bowel disease. The naked mole-rat (Heterocephalus glaber) shows no pain-related behaviour to subcutaneous acid injection and cutaneous afferents are insensitive to acid, an adaptation thought to be a consequence of the subterranean, likely hypercapnic, environment in which it lives. As such we sought to investigate naked mole-rat interoception within the gastrointestinal tract and how this differed from the mouse (Mus Musculus). Here, we show the presence of calcitonin gene-related peptide expressing extrinsic nerve fibres innervating both mesenteric blood vessels and the myenteric plexi of the smooth muscle layers of the naked mole-rat colorectum. Using ex vivo colonic-nerve electrophysiological recordings, we show differential sensitivity of naked mole-rat, compared to mouse, colonic afferents to acid and the prototypic inflammatory mediator bradykinin, but not direct mechanical stimuli. In naked mole-rat, but not mouse, we observed mechanical hypersensitivity to acid, whilst both species sensitised to bradykinin. Collectively, these findings suggest that naked mole-rat colonic afferents are capable of detecting acidic stimuli; however, their intracellular coupling to downstream molecular effectors of neuronal excitability and mechanotransduction likely differs between species.The authors declare no competing financial interests. This work was supported by Rosetrees Postdoctoral Grant (A1296; JRFH and EStJS), BBSRC grant (BB/R006210/1; JRFH and EStJS), Versus Arthritis Pain Challenge Grant (RG21973; GC and EStJS), AstraZeneca PhD studentshipt (KHB), EMBO Long-Term Fellowship (ALTF1565-2015; ZH) and University of Cambridge Vice Chancellor’s Award (TST)

Who bears the cost of forest conservation?

Background While the importance of conserving ecosystems for sustainable development is widely recognized, it is increasingly evident that despite delivering global benefits, conservation often comes at local cost. Protected areas funded by multilateral lenders have explicit commitments to ensure that those negatively affected are adequately compensated. We make the first comparison of the magnitude and distribution of the local costs of a protected area with the magnitude and distribution of the compensation provided under the World Bank social safeguard policies (Performance Standard 5). Methods In the Ankeniheny-Zahamena Corridor (a new protected area and REDD+ pilot project in eastern Madagascar), we used choice experiments to estimate local opportunity costs (n = 453) which we annualized using a range of conservative assumptions concerning discount rates. Detailed surveys covering farm inputs and outputs as well as off-farm income (n = 102) allowed us to explore these opportunity costs as a proportion of local incomes. Intensive review of publically available documents provided estimates of the number of households that received safeguard compensation and the amount spent per household. We carried out a contingent valuation exercise with beneficiaries of this compensation two years after the micro-development projects were implemented (n = 62) to estimate their value as perceived by beneficiaries. Results Conservation restrictions result in very significant costs to forest communities. The median net present value of the opportunity cost across households in all sites was US$2,375. When annualized, these costs represent 27–84% of total annual income for median-income households; significantly higher proportionally for poorer households. Although some households have received compensation, we conservatively estimate that more than 50% of eligible households (3,020 households) have not. Given the magnitude of compensation (based both on amount spent and valuation by recipients two years after the compensation was distributed) relative to costs, we argue that no one was fully compensated. Achieving full compensation will require an order of magnitude more than was spent but we suggest that this should be affordable given the global value of forest conservation. Discussion By analyzing in unprecedented depth both the local costs of conservation, and the compensation distributed under donor policies, we demonstrate that despite well-intentioned policies, some of the poorest people on the planet are still bearing the cost of forest conservation. Unless significant extra funding is provided by the global beneficiaries of conservation, donors’ social safeguarding requirements will not be met, and forest conservation in developing countries will jeopardize, rather than contribute to, sustainable development goals

Single-cell RNAseq reveals seven classes of colonic sensory neuron.

OBJECTIVE: Integration of nutritional, microbial and inflammatory events along the gut-brain axis can alter bowel physiology and organism behaviour. Colonic sensory neurons activate reflex pathways and give rise to conscious sensation, but the diversity and division of function within these neurons is poorly understood. The identification of signalling pathways contributing to visceral sensation is constrained by a paucity of molecular markers. Here we address this by comprehensive transcriptomic profiling and unsupervised clustering of individual mouse colonic sensory neurons. DESIGN: Unbiased single-cell RNA-sequencing was performed on retrogradely traced mouse colonic sensory neurons isolated from both thoracolumbar (TL) and lumbosacral (LS) dorsal root ganglia associated with lumbar splanchnic and pelvic spinal pathways, respectively. Identified neuronal subtypes were validated by single-cell qRT-PCR, immunohistochemistry (IHC) and Ca2+-imaging. RESULTS: Transcriptomic profiling and unsupervised clustering of 314 colonic sensory neurons revealed seven neuronal subtypes. Of these, five neuronal subtypes accounted for 99% of TL neurons, with LS neurons almost exclusively populating the remaining two subtypes. We identify and classify neurons based on novel subtype-specific marker genes using single-cell qRT-PCR and IHC to validate subtypes derived from RNA-sequencing. Lastly, functional Ca2+-imaging was conducted on colonic sensory neurons to demonstrate subtype-selective differential agonist activation. CONCLUSIONS: We identify seven subtypes of colonic sensory neurons using unbiased single-cell RNA-sequencing and confirm translation of patterning to protein expression, describing sensory diversity encompassing all modalities of colonic neuronal sensitivity. These results provide a pathway to molecular interrogation of colonic sensory innervation in health and disease, together with identifying novel targets for drug development

Functional and Molecular Characterization of Mechanoinsensitive "Silent" Nociceptors.

Mechanical and thermal hyperalgesia (pain hypersensitivity) are cardinal signs of inflammation. Although the mechanism underlying thermal hyperalgesia is well understood, the cellular and molecular basis of mechanical hyperalgesia is poorly described. Here, we have identified a subset of peptidergic C-fiber nociceptors that are insensitive to noxious mechanical stimuli under normal conditions but become sensitized to such stimuli when exposed to the inflammatory mediator nerve growth factor (NGF). Strikingly, NGF did not affect mechanosensitivity of other nociceptors. We show that these mechanoinsensitive "silent" nociceptors are characterized by the expression of the nicotinic acetylcholine receptor subunit alpha-3 (CHRNA3) and that the mechanically gated ion channel PIEZO2 mediates NGF-induced mechanosensitivity in these neurons. Retrograde tracing revealed that CHRNA3+ nociceptors account for ∼50% of all peptidergic nociceptive afferents innervating visceral organs and deep somatic tissues. Hence, our data suggest that NGF-induced "un-silencing" of CHRNA3+ nociceptors significantly contributes to the development of mechanical hyperalgesia during inflammation