15,397 research outputs found
Consent and the Construction of the Volunteer: Institutional Settings of Experimental Research on Human Beings in Britain during the Cold War
This study challenges the primacy of consent in the history of human experimentation and argues that privileging the cultural frameworks adds nuance to our understanding of the construction of the volunteer in the period 1945 to 1970. Historians and bio-ethicists have argued that medical ethics codes have marked out the parameters of using people as subjects in medical scientific research and that the consent of the subjects was fundamental to their status as volunteers. However, the temporality of the creation of medical ethics codes means that they need to be understood within their historical context. That medical ethics codes arose from a specific historical context rather than a concerted and conscious determination to safeguard the well-being of subjects needs to be acknowledged. The British context of human experimentation is under-researched and there has been even less focus on the cultural frameworks within which experiments took place. This study demonstrates, through a close analysis of the Medical Research Council's Common Cold Research Unit (CCRU) and the government's military research facility, the Chemical Defence Experimental Establishment, Porton Down (Porton), that the `volunteer' in human experiments was a subjective entity whose identity was specific to the institution which recruited and made use of the subject. By examining representations of volunteers in the British press, the rhetoric of the government's collectivist agenda becomes evident and this fed into the institutional construction of the volunteer at the CCRU. In contrast, discussions between Porton scientists, staff members, and government officials demonstrate that the use of military personnel in secret chemical warfare experiments was far more complex. Conflicting interests of the military, the government and the scientific imperative affected how the military volunteer was perceived
Before the Creation of Time in Platoâs Timaeus
I defend, against its more recent critics, a literal, factual, and consistent interpretation of Timaeusâ creation of the cosmos and time. My main purpose is to clarify the assumptions under which a literal interpretation of Timaeusâ cosmology becomes philosophically attractive. I propose five exegetical principles that guide my interpretation. Unlike previous literalists, I argue that assuming a âpre-cosmic timeâ is a mistake. Instead, I challenge the exegetical assumptions scholars impose on the text and argue that for Timaeus, a mere succession of events and the relations derived from it (before, after, simultaneous with) imply no time, given the narrow definition of the term used in the dialogue. For Timaeus, I explain, time is measurable, regular, and dependent on the motion of the celestial bodies. A mere succession of events like the one needed to understand the creation story and the pre-cosmos requires none of these elements. Readers of Plato erroneously assume that a succession of events implies time, but that is to impose a conception of time absent in the text. The chapter offers a detailed reconstruction of the pre-cosmic stage under a literalist interpretation and argues how it is compatible with the immutable relationship between the Demiurge and the cosmos.
This is an open access chapter distributed under the terms of the CC BY-NC 4.0 license. chapter
Strategies for Early Learners
Welcome to learning about how to effectively plan curriculum for young children. This textbook will address: âą Developing curriculum through the planning cycle âą Theories that inform what we know about how children learn and the best ways for teachers to support learning âą The three components of developmentally appropriate practice âą Importance and value of play and intentional teaching âą Different models of curriculum âą Process of lesson planning (documenting planned experiences for children) âą Physical, temporal, and social environments that set the stage for childrenâs learning âą Appropriate guidance techniques to support childrenâs behaviors as the self-regulation abilities mature. âą Planning for preschool-aged children in specific domains including o Physical development o Language and literacy o Math o Science o Creative (the visual and performing arts) o Diversity (social science and history) o Health and safety âą Making childrenâs learning visible through documentation and assessmenthttps://scholar.utc.edu/open-textbooks/1001/thumbnail.jp
Building body identities - exploring the world of female bodybuilders
This thesis explores how female bodybuilders seek to develop and maintain a viable sense of self despite being stigmatized by the gendered foundations of what Erving Goffman (1983) refers to as the 'interaction order'; the unavoidable presentational context in which identities are forged during the course of social life. Placed in the context of an overview of the historical treatment of women's bodies, and a concern with the development of bodybuilding as a specific form of body modification, the research draws upon a unique two year ethnographic study based in the South of England, complemented by interviews with twenty-six female bodybuilders, all of whom live in the U.K. By mapping these extraordinary women's lives, the research illuminates the pivotal spaces and essential lived experiences that make up the female bodybuilder. Whilst the women appear to be embarking on an 'empowering' radical body project for themselves, the consequences of their activity remains culturally ambivalent. This research exposes the 'Janus-faced' nature of female bodybuilding, exploring the ways in which the women negotiate, accommodate and resist pressures to engage in more orthodox and feminine activities and appearances
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Co-design As Healing: Exploring The Experiences Of Participants Facing Mental Health Problems
This thesis is an exploration of the healing role of co-design in mental health. Although co-design projects conducted within mental health settings are rising, existing literature tends to focus on the object of design and its outcomes while the experiences of participants per se remain largely unexplored. The guiding research question of this study is not how we design things that improve mental health, but how co-designing, as an act, might do so.
The thesis presents two projects that were organized in collaboration with the mental health charity Islington Mind and the Psychosis Therapy Project (PTP) in London.
The project at Islington Mind used a structured design process inviting participants to design for wellbeing. A case study analysis provides insights on how participants were impacted, summarizing key challenges and opportunities.
The design at PTP worked towards creating a collective brief in an emergent fashion, finally culminating in a board game. The experiences of participants were explored through Interpretative Phenomenological Analysis (IPA), using semi-structured interview data. The analysis served to identify key themes characterising the experience of co-design such as contributing, connecting, thinking and intentioning. In addition, a mixed-methods analysis of questionnaires and interview data exploring participants' wellbeing, showed that all participants who engaged fairly consistently in the project improved after the project ended, although some participants' scores returned to baseline six months later.
Reflecting on both projects, an approach to facilitation within mental health is outlined, detailing how the dimensions of weaving and layered participation, nurturing mattering and facilitating attitudes interlace. This contribution raises awareness of tacit dimensions in the practice of facilitation, articulating the nuances of how to encourage and sustain meaningful and ethical engagement and offering insights into a range of tools. It highlights the importance of remaining reflexive in relation to attitudes and emotions and discusses practical methodological and ethical challenges and ways to resolve them which can be of benefit to researchers embarking on a similar journey.
The thesis also offers detailed insights on how methodologies from different fields were integrated into a whole, arguing for transparency and reflexivity about epistemological assumptions, and how underlying paradigms shift in an interdisciplinary context.
Based on the overall findings, the thesis makes a case for considering design as healing (or a designerly way of healing), highlighting implications at a systems, social and individual level. It makes an original contribution to our understanding of design, highlighting its healing character, and proposes a new way to support mental health. The participants in this study not only had increased their own wellbeing through co-designing, but were also empowered and contributed towards healing the world. Hence, the thesis argues for a unique, holistic perspective of design and mental health, recognizing the interconnectedness of the individual, social and systemic dimensions of the healing processes that are ignited
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Meaning-Making Practices of Emergent ArabicâEnglish Bilingual Kindergarten Children in Cairo
The number of British Schools in the Middle East and North Africa (MENA) region is growing. The National Curriculum of England is used by an increasing number of such schools. As well as exporting a culturally-specific curriculum, these schools usually adopt an ideology of monolingualism, thus potentially limiting communication for emergent bilinguals and failing to acknowledge the multiple ways of meaning-making.
Current studies of translanguaging are moving the focus to multimodal forms of communication as a resource for thinking and communicating (GarcĂa and Wei 2014, Wei 2018). Building on the work of Kress (1997, 2010) I explore pre-school emergent bilingualsâ wider signifying practices and create an analytical framework, which I call MMTL (multimodal translanguaging), used as a lens to illustrate meaning-making.
Valley Hill in Cairo, Egypt is a British school which encourages âEnglish-onlyâ as the medium of instruction in the kindergarten. Using a case study methodology, this research explores the meaning-making practices of eight emergent bilingual children aged 3â4 during child-initiated play, later reduced to four in the thesis to provide a detailed multimodal analysis. The principal aim is to explore their speech, gaze, gesture, and their engagement (layout/position) with artefacts during play.
The findings of this study suggest that although there is an âEnglish-onlyâ approach, these young emergent bilingual children are meaning-making in a variety of ways. Children are translanguaging but it is never in isolation from other modes of communication. Emergent bilinguals use a range of modes to mediate their understanding and communication with others. They use gesture, gaze, and artefacts alongside translingual practices to move meaning across to more accessible modes, enabling communication and understanding. The implications for schools should be to embrace such hybrid practices and for teachers to be more responsive to young childrenâs meaning-making to enable learning
Image classification over unknown and anomalous domains
A longstanding goal in computer vision research is to develop methods that are simultaneously applicable to a broad range of prediction problems. In contrast to this, models often perform best when they are specialized to some task or data type. This thesis investigates the challenges of learning models that generalize well over multiple unknown or anomalous modes and domains in data, and presents new solutions for learning robustly in this setting.
Initial investigations focus on normalization for distributions that contain multiple sources (e.g. images in different styles like cartoons or photos). Experiments demonstrate the extent to which existing modules, batch normalization in particular, struggle with such heterogeneous data, and a new solution is proposed that can better handle data from multiple visual modes, using differing sample statistics for each.
While ideas to counter the overspecialization of models have been formulated in sub-disciplines of transfer learning, e.g. multi-domain and multi-task learning, these usually rely on the existence of meta information, such as task or domain labels. Relaxing this assumption gives rise to a new transfer learning setting, called latent domain learning in this thesis, in which training and inference are carried out over data from multiple visual domains, without domain-level annotations. Customized solutions are required for this, as the performance of standard models degrades: a new data augmentation technique that interpolates between latent domains in an unsupervised way is presented, alongside a dedicated module that sparsely accounts for hidden domains in data, without requiring domain labels to do so.
In addition, the thesis studies the problem of classifying previously unseen or anomalous modes in data, a fundamental problem in one-class learning, and anomaly detection in particular. While recent ideas have been focused on developing self-supervised solutions for the one-class setting, in this thesis new methods based on transfer learning are formulated. Extensive experimental evidence demonstrates that a transfer-based perspective benefits new problems that have recently been proposed in anomaly detection literature, in particular challenging semantic detection tasks
RNA pull-down-confocal nanoscanning (RP-CONA), a novel method for studying RNA/protein interactions in cell extracts that detected potential drugs for Parkinsonâs disease targeting RNA/HuR complexes
MicroRNAs (miRNAs, miRs) are a class of small non-coding RNAs that regulate gene expression through specific base-pair targeting. The functional mature miRNAs usually undergo a two-step cleavage from primary miRNAs (pri-miRs), then precursor miRNAs (pre-miRs). The biogenesis of miRNAs is tightly controlled by different RNA-binding proteins (RBPs). The dysregulation of miRNAs is closely related to a plethora of diseases. Targeting miRNA biogenesis is becoming a promising therapeutic strategy.
HuR and MSI2 are both RBPs. MiR-7 is post-transcriptionally inhibited by the HuR/MSI2 complex, through a direct interaction between HuR and the conserved terminal loop (CTL) of pri-miR-7-1. Small molecules dissociating pri-miR-7/HuR interaction may induce miR-7 production. Importantly, the miR-7 levels are negatively correlated with Parkinsonâs disease (PD).
PD is a common, incurable neurodegenerative disease causing serious motor deficits. A hallmark of PD is the presence of Lewy bodies in the human brain, which are inclusion bodies mainly composed of an aberrantly aggregated protein named α-synuclein (α-syn). Decreasing α-syn levels or preventing α-syn aggregation are under investigation as PD treatments. Notably, α-syn is negatively regulated by several miRNAs, including miR-7, miR-153, miR-133b and others. One hypothesis is that elevating these miRNA levels can inhibit α-syn expression and ameliorate PD pathologies.
In this project, we identified miR-7 as the most effective α-syn inhibitor, among the miRNAs that are downregulated in PD, and with α-syn targeting potentials. We also observed potential post-transcriptional inhibition on miR-153 biogenesis in neuroblastoma, which may help to uncover novel therapeutic targets towards PD.
To identify miR-7 inducers that benefit PD treatment by repressing α-syn expression, we developed a novel technique RNA Pull-down Confocal Nanoscaning (RP-CONA) to monitor the binding events between pri-miR-7 and HuR. By attaching FITC-pri-miR-7-1-CTL-biotin to streptavidin-coated agarose beads and incubating them in human cultured cell lysates containing overexpressed mCherry-HuR, the bound RNA and protein can be visualised as quantifiable fluorescent rings in corresponding channels in a confocal high-content image system. A pri-miR-7/HuR inhibitor can decrease the relative mCherry/FITC intensity ratio in RP-CONA. With this technique, we performed several small-scale screenings and identified that a bioflavonoid, quercetin can largely dissociate the pri-miR-7/HuR interaction. Further studies proved that quercetin was an effective miR-7 inducer as well as α-syn inhibitor in HeLa cells.
To understand the mechanism of quercetin mediated α-syn inhibition, we tested the effects of quercetin treatment with miR-7-1 and HuR knockout HeLa cells. We found that HuR was essential in this pathway, while miR-7 hardly contributed to the α-syn inhibition. HuR can directly bind an AU-rich element (ARE) at the 3â untranslated region (3â-UTR) of α-syn mRNA and promote translation. We believe quercetin mainly disrupts the ARE/HuR interaction and disables the HuR-induced α-syn expression.
In conclusion, we developed and optimised RP-CONA, an on-bead, lysate-based technique detecting RNA/protein interactions, as well as identifying RNA/protein modulators. With RP-CONA, we found quercetin inducing miR-7 biogenesis, and inhibiting α-syn expression. With these beneficial effects, quercetin has great potential to be applied in the clinic of PD treatment. Finally, RP-CONA can be used in many other RNA/protein interactions studies
TOWARDS AN UNDERSTANDING OF EFFORTFUL FUNDRAISING EXPERIENCES: USING INTERPRETATIVE PHENOMENOLOGICAL ANALYSIS IN FUNDRAISING RESEARCH
Physical-activity oriented community fundraising has experienced an exponential growth in popularity over the past 15 years. The aim of this study was to explore the value of effortful fundraising experiences, from the point of view of participants, and explore the impact that these experiences have on peopleâs lives. This study used an IPA approach to interview 23 individuals, recognising the role of participants as proxy (nonprofessional) fundraisers for charitable organisations, and the unique organisation donor dynamic that this creates. It also bought together relevant psychological theory related to physical activity fundraising experiences (through a narrative literature review) and used primary interview data to substantiate these. Effortful fundraising experiences are examined in detail to understand their significance to participants, and how such experiences influence their connection with a charity or cause. This was done with an idiographic focus at first, before examining convergences and divergences across the sample. This study found that effortful fundraising experiences can have a profound positive impact upon community fundraisers in both the short and the long term. Additionally, it found that these experiences can be opportunities for charitable organisations to create lasting meaningful relationships with participants, and foster mutually beneficial lifetime relationships with them. Further research is needed to test specific psychological theory in this context, including self-esteem theory, self determination theory, and the martyrdom effect (among others)
Identification of Hindbrain Neural Substrates for Motor Initiation in the hatchling Xenopus laevis Tadpole
Animal survival profoundly depends on the ability to detect stimuli in the environment, process them and respond accordingly. In this respect, motor responses to a sensory stimulation evolved into a variety of coordinated movements, which involve the control of brain centres over spinal locomotor circuits. The hatchling Xenopus tadpole, even in its embryonic stage, is able to detect external sensory information and to swim away if the stimulus is considered noxious. To do so, the tadpole relies on well-known ascending sensory pathway, which carries the sensory information to the brain. When the stimulus is strong enough, descending interneurons are activated, leading to the excitation of spinal CPG neurons, which causes the undulatory movement of swimming. However, the activation of descending interneurons that marks the initiation of motor response appears after a long delay from the sensory stimulation. Furthermore, the long-latency response is variable in time, as observed in the slow-summating excitation measured in descending interneurons. These two features, i.e. long-latency and variability, cannot be explained by the firing time and pattern of the ascending sensory pathway of the Xenopus tadpole. Therefore, a novel neuronal population has been proposed to lie in the hindbrain of the tadpole, and being able to 'hold' the sensory information, thus accounting for the long and variable delay of swim initiation. In this work, the role of the hindbrain in the maintenance of the long and variable response to trunk skin stimulation is investigated in the Xenopustadpole at developmental stage 37/38. A multifaceted approach has been used to unravel the neuronal mechanisms underlying the delayed motor response, including behavioural experiments, electrophysiology analysis of fictive swimming, hindbrain extracellular recordings and imaging experiments. Two novel neuronal populations have been identified in the tadpole's hindbrain, which exhibit activation patterns compatible with the role of delaying the excitation of the spinal locomotor circuit. Future work on cellular properties and synaptic connections of these newly discovered populations might shed light on the mechanism of descending control active at embryonic stage. Identifying supraspinal neuronal populations in an embryonic organism could aid in understanding mechanisms of descending motor control in more complex vertebrates
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