Top-down amplification of predicted visual input behind a frosted occluder

This thesis is comprised of five chapters. It includes two experimental chapters in which I detail both psychophysical and fMRI studies carried out at the University of Glasgow as part of this PhD project. These are followed by a literature review which outlines the implementation of ultra-high-resolution fMRI, both generally within the field and within a specific project proposal. Chapter 1 is a general introduction. I outline the broad organisation and basic functions of the visual system at the pre-cortical and cortical stages, in turn. I then discuss the concept of feedback within the visual system, outlining what feedback is, what it does and how it is implemented before outlining the rationale for the thesis. Chapter 2 is an experimental chapter detailing a series of psychophysical experiments. These experiments employ a partial occlusion paradigm to explore how top-down predicted information can influence the processing of degraded feedforward input. Throughout the experimental series, different aspects of this question are addressed in order to investigate whether the consistency of contextual information influences the detection and/or recognition of low-contrast visual scenes. Chapter 3 is another experimental chapter which details two 3T fMRI experiments. These projects also employed a partial occlusion paradigm to investigate contextual modulation on the processing of degraded feedforward input at the neuronal level in early visual cortex. Both univariate and multivariate analysis techniques were used to reveal the impact of consistency within top-down information. Chapter 4 contains a literature review which looks into ultra-high-resolution fMRI. Here, I detail the motivation behind the development of higher resolution imaging as well as potential confounds and limitations. I also outline adaptations required at higher resolution in terms of data acquisition and analysis as well as briefly exploring layer-specific findings within the visual cortex. Finally, I propose a 7T fMRI project that would continue to explore the influence of top-down predictions on the processing of degraded visual input by expanding the investigation to a laminar level. Chapter 5 is a general discussion which summarises the key points from each of the previous chapters and briefly discusses their conceptual relation to the current field and beyond

Occupational therapy-led pulmonary rehabilitation: A practice analysis

Statement of context: Pulmonary rehabilitation is accepted as an essential strategy for the management of respiratory disease. However, there is wide variation in models of service delivery, and evidence to understand which elements are most effective is less clear. This analysis outlines key elements of an occupational therapy-led pulmonary rehabilitation programme. Critical reflection on practice: It is proposed that the core focus on occupation and the unique skills and reasoning of occupational therapists contribute to positive outcomes for service users. Implications for practice: Occupational therapists are ideally placed to lead and develop pulmonary rehabilitation programmes. As there is genuine uncertainty about which elements are most effective, this analysis should encourage further evaluation and research

A long and winding road: The hard graft of scaling social change in complex systems

Advice abounds on how to implement large-scale social change, much of which emphasizes a simplistic linear process, led by a heroic central actor. Rigorous case studies have shown that social change is far more complex: it is a reciprocal, iterative, and adaptive process, with multiple stakeholders who work backstage in networked, committed teams. Despite this, the myth of the social entrepreneur as a transformative change maker capable of scaling innovations to a societal level, still holds sway over social innovation support programmes and business school curricula. Using illustrative examples of successful efforts of large-scale social change across three of the most pressing international social challenges: access to medicines, the integration of migrant populations, and reorganizing social care models, we illustrate how conceptualizing social change as driven by iconic individuals is often counter-productive in terms of achieving impact at a societal level. Based on these analyses, we present five insights which illustrate how the mythology of social entrepreneurship and simplistic scaling concepts are often contrary to the practices employed within successful efforts to bring about social impact. Three counteracting principles for those leading, evaluating and funding innovative change efforts within complex systems are discussed and contrasted with the pervasive mythology of social entrepreneurship and linear scaling processes

Service Group Management facilitated by DSL driven Policies in embedded Middleware

Middleware by its very nature is fundamental to the functioning of systems as it provides the communication between software components. It is very much an underlying technology and is rarely visible to end users. As systems develop, certain domain semantics, provided by the domain experts, need to be injected into the behaviour of the underlying middleware, but in a controlled manner. The methods used to achieve this are often static in nature, wholly dependent on how they are implemented, deployed and managed. An increasingly popular way to manage this behaviour injection is through the use of policies, a technique used to govern defined rules, triggered by associated events, resulting in specific actions when certain conditions are encountered. Strong efforts have been made throughout the evolution of software development methods and programming languages to solve the lack of dynamicity which can arise through poor practices. Successive language based attempts to attain a higher level of abstraction in the notations used and techniques deployed have resulted in the re-discovery of Domain Specific Languages (DSL). This paper looks at injecting the dynamicity required in the management of service groups through a policy based DSL

Dissolving microneedles for intradermal vaccination against shigellosis

Intradermal (ID) immunization is of increasing interest due to the easy accessibility and excellent immunogenic properties of the skin. Among ID immunization methods, dissolving microneedles (MNs) have appeared as an alternative to traditional hypodermic immunization, offering many advantages, such as being an easily administered method, with no need for health personnel, painless, and avoiding the use of needles and sharp wastage. In this study, an affordable and easy-to-produce MNs method was developed based on aqueous blends of 30% w/w poly (methyl vinyl ether-co-maleic anhydride). As an antigen model, a subunit vaccine candidate based on outer membrane vesicles from Shigella flexneri was used. Both unloaded and antigen-loaded MNs were synthetized and characterized. The MNs were successfully validated in an in vitro Parafilm M skin model and in a pig skin ex vivo model. Biodistribution studies were performed in BALB/c mice using 99mTcO4- radiolabeled samples. Results indicated that the vesicle vaccine was successfully released from the MNs and targeted gastrointestinal tract after 6 h post-administration. In vivo immunization and protection studies were performed in BALB/c mice. Mice were intradermally immunized through ear skin with one single dose of 200 g antigenic complex, eliciting the production of specific systemic IgG and mucosal IgA

The role of rapid diagnostics in managing Ebola epidemics

Ebola emerged in West Africa around December 2013 and swept through Guinea, Sierra Leone and Liberia, giving rise to 27,748 confirmed, probable and suspected cases reported by 29 July 2015. Case diagnoses during the epidemic have relied on polymerase chain reaction-based tests. Owing to limited laboratory capacity and local transport infrastructure, the delays from sample collection to test results being available have often been 2 days or more. Point-of-care rapid diagnostic tests offer the potential to substantially reduce these delays. We review Ebola rapid diagnostic tests approved by the World Health Organization and those currently in development. Such rapid diagnostic tests could allow early triaging of patients, thereby reducing the potential for nosocomial transmission. In addition, despite the lower test accuracy, rapid diagnostic test-based diagnosis may be beneficial in some contexts because of the reduced time spent by uninfected individuals in health-care settings where they may be at increased risk of infection; this also frees up hospital beds. We use mathematical modelling to explore the potential benefits of diagnostic testing strategies involving rapid diagnostic tests alone and in combination with polymerase chain reaction testing. Our analysis indicates that the use of rapid diagnostic tests with sensitivity and specificity comparable with those currently under development always enhances control, whether evaluated at a health-care-unit or population level. If such tests had been available throughout the recent epidemic, we estimate, for Sierra Leone, that their use in combination with confirmatory polymerase chain-reaction testing might have reduced the scale of the epidemic by over a third

Assessing functional reorganization in visual cortex with simulated retinal lesions

Macular degeneration (MD) causes central vision loss, removing input to corresponding representations in the primary visual cortex. There is disagreement concerning whether the cortical regions deprived of input can remain responsive, and the source of reported cortical responses is still debated. To simulate MD in controls, normally sighted participants viewed a bright central disk to adapt the retina, creating a transient 'retinal lesion' during a functional MRI experiment. Participants viewed blocks of faces, scrambled faces and uniform grey stimuli, either passively or whilst performing a one-back task. To assess the impact of the simulated lesion, participants repeated the paradigm using a more conventional mean luminance simulated scotoma without adaptation. Our results suggest our attempt to create a more realistic simulation of a lesion did not impact on responses in the representation of the simulated lesion. While most participants showed no evidence of stimulus-driven activation within the lesion representation, a few individuals (22%) exhibited responses similar to a participant with juvenile MD who completed the same paradigm (without adaptation). Reliability analysis showed that responses in the representation of the lesion were generally consistent irrespective of whether positive or negative. We provide some evidence that peripheral visual stimulation can also produce responses in central representations in controls while performing a task. This suggests that the 'signature of reorganization of visual processing', is not found solely in patients with retinal lesions, consistent with the idea that activity may be driven by unmasked top-down feedback

A simple approach to measure transmissibility and forecast incidence

Outbreaks of novel pathogens such as SARS, pandemic influenza and Ebola require substantial investments in reactive interventions, with consequent implementation plans sometimes revised on a weekly basis. Therefore, short-term forecasts of incidence are often of high priority. In light of the recent Ebola epidemic in West Africa, a forecasting exercise was convened by a network of infectious disease modellers. The challenge was to forecast unseen “future” simulated data for four different scenarios at five different time points. In a similar method to that used during the recent Ebola epidemic, we estimated current levels of transmissibility, over variable time-windows chosen in an ad hoc way. Current estimated transmissibility was then used to forecast near-future incidence. We performed well within the challenge and often produced accurate forecasts. A retrospective analysis showed that our subjective method for deciding on the window of time with which to estimate transmissibility often resulted in the optimal choice. However, when near-future trends deviated substantially from exponential patterns, the accuracy of our forecasts was reduced. This exercise highlights the urgent need for infectious disease modellers to develop more robust descriptions of processes – other than the widespread depletion of susceptible individuals – that produce non-exponential patterns of incidence