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Comparative study of antiviral IFITM proteins in reservoir bat species
No full textSpecies-specific innate immune responses are shaped by the virus-host arms race and contribute to the species barrier against zoonosis. Interferon-induced transmembrane proteins (IFITMs) are key players in the antiviral interferon response and act by inhibiting viral entry. The unique IFITM repertoires of different species may influence their resistance to viral infections. Bats are reservoir hosts for many zoonotic viruses and their enhanced antiviral immunity has been proposed to be important for this, but whether IFITMs play a role is unclear. In this thesis, the comparative analysis of mammalian IFITM families reveals frequent IFITM gene duplication events, highlighting the importance of IFITM diversity as a component of innate immunity. An important functional motif, the amphipathic helix, has reduced amphipathicity in bat IFITMs which is predicted to alter their antiviral activity. Characterisation of IFITMs in Chinese rufous horseshoe bat, a natural host of SARS-related coronaviruses, shows that alternatively spliced IFITM isoforms can exhibit distinct antiviral specificities against influenza A virus, Nipah virus and coronaviruses including MERS-CoV, SARS-CoV and SARS-CoV-2. Besides their antiviral function, IFITMs can modulate interferon production, suggesting that they have effects beyond restricting viral entry that may also influence viral immunopathogenesis. Further bioinformatic analysis in 206 mammals reveals that IFITM alternative splicing is an underappreciated evolutionary strategy to generate diversity and is more prevalent in bats relative to other mammals. Increased frequency of alternative splicing is also evident in immune-related genes in humans which is consistent with the selection pressures imposed by the virus-host arms race. These findings identify alternative splicing as a key source of functional innovation in immunity and a strategy that may be used by reservoir bat species to fine-tune their antiviral immune response by regulating the expression of functionally distinct IFITM isoforms. My comparative analysis showcases the power of this approach to uncover novel features of gene functions. Similar studies to understand the unique antiviral immune responses in bats can guide the development of therapeutic strategies to treat viral infections and immunopathologies
Exploring the relationship between child deprivation and access to schools in Tanzania
No full textEducational access remains highly unequal in low-income countries, where physical distance to schools reinforces poverty, gender inequality, and rural disadvantage. This study integrates high-resolution (100-metre) travel time modelling with nationally representative Demographic and Health Survey (DHS) data to examine how geographic barriers and household factors shape educational deprivation in Tanzania. Using least-cost path algorithms, travel time surfaces to the nearest primary and secondary schools were generated and linked to DHS data for over 24,000 children aged 7 to 19. Educational deprivation was defined as never having attended school, based on indicator HV121.
Logistic regression models showed that children living beyond recommended thresholds (45 minutes for primary, 60 minutes for secondary) had significantly higher odds of non-attendance, particularly in rural and low-income households. Maternal education was a strong protective factor across both age groups. Spatial analysis identified regional clusters of deprivation in southern and western Tanzania. Reintegration of excluded cross-border schools corrected anomalies near international boundaries and restored expected trends among wealthier groups.
The findings highlight the importance of addressing both spatial and socioeconomic inequalities in education policy. Limitations include the use of a binary attendance measure, lack of quality indicators, and omission of seasonal disruptions. Future work should incorporate dynamic environmental data and more detailed educational indicators to better support inclusive and equitable service delivery
Functional and exercise capacity, fatigue, and accelerometry in the early post-ICU recovery period
No full textResearch on post-critical illness outcomes has grown significantly, revealing that many survivors experience long-term physical, mental, and cognitive challenges, accompanied by persistent and burdensome symptoms, such as fatigue. Regaining functional capacity is a top priority for patients, yet the experience of fatigue and low energy, despite the availability of several measuring tools, is often overlooked in research. Several objective methods are used to assess functional and exercise capacity, with the cardiopulmonary exercise test (CPET) considered the gold standard, while accelerometry/actigraphy is emerging as a valuable tool for assessing physical activity and sleep in clinical research. This thesis explores the utility of cardiopulmonary exercise testing (CPET), accelerometry, and the assessment of fatigue and energy in post-critical illness patients. It aims to address the following primary research questions: (1) To what extent are CPET and accelerometry currently utilised in this population? and (2) What is the feasibility of conducting CPET, implementing long-term wrist-worn accelerometry, and assessing fatigue and energy levels using the Visual Analogue Scale for Fatigue in patients shortly after ICU discharge? The background and context were reviewed in Chapter 1.
Chapter 2 describes a systematic literature review of existing studies on CPET testing in post-critical illness survivors, focusing on exercise-related oxygen consumption rates and causes of exercise limitations. Eight studies involving 207 patients, were analysed. Study quality ranged from fair to good, with variations in reporting. CPET timing ranged from 2 to 160 weeks post-hospitalisation. The pooled mean submaximal VO2 at 1 month was 14 (95% CI: 13.2, 14.7) ml/kg/min, and VO2 at the anaerobic threshold was 10.3 (95% CI: 9.7, 10.8) ml/kg/min, representing 56% (95% CI: 51%, 62%) of the predicted value. General deconditioning was the primary cause of functional impairment. No significant adverse events occurred during CPET. These findings suggest the underutilisation of this method in critical illness research and highlight a lack of knowledge regarding functional capacity assessment through CPET during the ICU-to-hospital discharge period.
Chapter 3 describes a scoping literature review, to examine the utility of accelerometer sensors published during the last 5 years in survivors of critical illness in the context of the post-ICU period. Eleven non-interventional studies were included; all conducted at varying times post-ICU discharge. There was significant variation in participant numbers, demographics, clinical characteristics, device brands, and body position. Most studies focused on physical activity behaviour, with less than 7 days of continuous monitoring, and notable inconsistency in reported behavioural measures and acceleration data analysis. These findings highlight the scarcity of data on long-term accelerometry use and the absence of a standardised approach to analysing and reporting acceleration data, limiting comparability between studies.
Chapter 4 describes a prospective clinical service evaluation to inform future studies by assessing functional status with the Barthel Index (BI) and perceived fatigue levels using the Visual Analogue Scale-Fatigue (VAS-F) in patients receiving routine care and rehabilitation after ICU discharge. Over two months, 39 out of 45 screened post-ICU patients were included, mostly male (64%), with a median age of 54 years (IQR [37, 61]) and a median ICU stay of 2.6 days (IQR [1.6, 3.9]). At one week post-ICU, 56% were highly dependent in basic daily tasks, while 28% were independent. Clinically significant fatigue was observed in 60% of patients, with a mean score of 6.2 (95% CI: [5.1, 7.3]). These findings suggest that the VAS-F is suitable for use in the early post-ICU period, and that some patients may be capable of performing CPET during their index hospital stay.
Chapter 5 describes a prospective non-interventional clinical study to: 1) Explore the utility of long-term continuous accelerometry/actigraphy in post-critical care patients; 2) Assess the feasibility of cardiopulmonary exercise testing in the early post-critical illness period; 3) Measure basic daily activity levels at ICU discharge and pre-hospital discharge; 4) Assess perceived fatigue and energy levels at ICU discharge and pre-hospital discharge; 5) Explore associations between physical activity, sleep (from accelerometer data), and fatigue, energy, and functional capacity. Twenty participants were recruited from 55 eligible patients, with a median age of 49 years (IQR [33, 61]), a median APACHE II score of 19 (IQR [12, 20]), and a median post-ICU stay of 10 days (IQR [8, 18]). Eighty percent of participants had at least 7 days of valid accelerometer data, with a mean recording duration of 32 (±16) days. Only 4 participants completed CPET. At enrolment, 65% of participants exhibited varying degrees of functional dependency, which improved by hospital discharge, with a mean BI score increase of 3.75 points (95% CI: 2.4, 4.9, p = 0.0004). Clinically relevant fatigue was present in 60% of participants at enrolment, decreasing to 10% at discharge, while low energy was reported by 55%, decreasing to 40% by discharge. Functional status was positively correlated with daily step count (rho = 0.5, p = 0.03) and negatively correlated with sedentary time (r = -0.5, p = 0.01). Sleep efficiency also showed a positive correlation (rho = 0.62, p = 0.0009). Clinically significant fatigue was associated with time spent in the supine position (tau = 0.6, p = 0.04). These findings suggest long-term accelerometry is feasible and informative for assessing recovery, while CPET is challenging to complete within the proposed timeframe.
Chapter 6 explored the agreement between behavioural measures produced by two accelerometer data analysis algorithms, the Activinsights GENEActiv R Markdown analysis tool (GENEA) and the Generalized Estimation of Activity and Posture (GGIR), on a single dataset. A total of 420 days of monitoring, each with over 20 hours of usable data per day, were analysed. For all physical activity and sleep behaviour measures assessed, Bland-Altman analysis revealed modest systematic bias with wide 95% limits of agreement, exceeding the proposed clinically meaningful difference in all cases except daily step count during hospitalisation. These findings suggested poor agreement in end-user output between the two raw acceleration data analysis approaches, questioning their validity in this population with low levels of physical activity.
In an individual case study series, chapter 7 explored whether clinical episodes of physical therapy undertaken during post-ICU hospital ward stay were adequately represented by relevant accelerometry-derived activity obtained using a freely available classification model. From the data collected in the previous study, 6 participants had a median of 3 days (range: 1-12) of valid accelerometer data on days with documented rehabilitation sessions in the medical records. A total of 25 days were analysed. In all cases, the activity suggested by the activity classification algorithm showed poor correspondence with the activity reported by the physiotherapist in the medical notes.
In Chapter 8, I discuss the thesis findings and how they contribute to the understanding of the challenges associated with performing CPET during hospitalisation and the feasibility of long-term accelerometry for continuous monitoring of physical activity and sleep behaviour. I highlight the need for further research to improve the accuracy and application of these tools in post-critical illness recovery.
COVID-19 Impact statement
Similar to the experience of many researchers in the clinical field, the COVID-19 pandemic and the resulting unprecedented measures affected the conduct and timeline of this PhD project. Key impacts included:
•Delays in participant recruitment and data collection: Due to restrictions imposed by both the ethics committee and research and development offices, reviews of all non-COVID-19-related research were postponed, creating a significant backlog of studies awaiting approval. Consequently, participant recruitment only commenced after pandemic-related constraints were lifted, which occurred markedly later than initially anticipated.
•Changes to study protocol: In the immediate post-pandemic period, recruitment proved challenging, likely due to the psychological aftermath of social distancing and isolation. As a result, several adaptations to the study protocol were required, which themselves took a prolonged time to be reviewed and approved by the responsible regulatory bodies.
Despite these challenges, the research proceeded with appropriate adjustments and continued to adhere to all ethical and safety standards. However, due to these unforeseen circumstances, only half of the targeted study sample was ultimately reached
Investigating cross-reactive antibodies to SARS-CoV-2 in pre-pandemic African samples
Get PDFThe SARS-CoV-2 pandemic had a profound global impact, yet Africa exhibited significantly lower
infection and mortality rates compared to other continents. This study explores the hypothesis
that pre-existing immunity may have contributed to this phenomenon. While factors like
demographics, lifestyle, and climate have been previously discussed, the potential role of crossreactive
immunity remains underexplored. We examined pre-pandemic sera collected in 2019 and
2003 from populations in Zimbabwe to assess levels of IgG and IgM antibodies that might crossreact
with SARS-CoV-2, particularly those targeting the spike protein. Using Rapid Detection
Tests (RDT) and ELISA assays, we investigated the prevalence and levels of these antibodies,
hypothesizing that prior exposure to other human coronaviruses or pathogens, may have provided
cross-protection against SARS-CoV-2. Our findings shed light on the immunological landscape in
Zimbabwe prior to the COVID-19 pandemic, contributing valuable insights into the possible
epidemiological factors that shaped Africa's response to the virus
Becoming ecophronetic: three projects in radical improvisation
Get PDFIn this practice-led research, I set out to model instances of sonic ecophronesis. This new category of sound-making, documented through this effort, embodies an approach to sound shaped not by aesthetic considerations in the first instance but by the desire to contribute creatively to emergent social and cultural needs. As a sonic artist and improviser, I thus conceive of sound-making through the values of Aristotelian phronesis—or practical wisdom, enabling the one who practises it to understand ‘the right way to do the right thing in a particular circumstance, with a particular person, at a particular time’ (Schwartz & Sharpe, 2010, p. 5-6)—and, further, through the ecological reorientation of phronesis toward the common good as
‘ecophronesis’ (Xiang, 2016).
Throughout the thesis, I use a practice-as-research framework to afford a privileged view into the sonic ecophronetic nexus, paying particular attention to how processes of reflection and discernment drove my approach to creative practices during this research. Adopting these dimensions in working with sound enabled me to become a polymathic sound practitioner and improviser, navigating a range of disciplinary domains whilst aiming to make timely contributions to the communities to which I belong. In turn, as I analyse, this necessitated a critical view towards improvisation—the central practice with which I contended to meet specific goals in each project—contributing to its ‘radicalisation’, a process of reappraisal through which it became infused with new functions and fresh possibilities for its application in the world.
This timely project brings attention to the changing roles inhabited by sonic artists today, expanding conceptualisations of how artists can become vital contributors within a range of disciplines, such as decolonisation, knowledge production, politics and more
Modelling bovine tuberculosis infection in stem cell-derived macrophages
Get PDFBovine tuberculosis is a serious disease in cattle which has significant
economic repercussions and poses a risk to human health. The pathogen
responsible, Mycobacterium bovis, is inhaled into the lungs and engulfed by
alveolar macrophages (AMs). The early interactions between M. bovis and the
AMs are complex and are crucial in determining the outcome of infection. Whilst the AMs have numerous mechanisms to eliminate pathogens including
the production of antimicrobials and cytokines, M. bovis can subvert these
processes and create an environment within the AM where the bacteria can
thrive. It is important to investigate M. bovis- macrophage interactions as this
may lead to the identification of potential targets for intervention. In order to
study these interactions, a suitable cell culture model is required which
resembles the macrophages found within the calf lung as closely as possible.
Here, an efficient and reliable system has been developed to study M. bovis
infection using bovine embryonic stem cell-derived macrophages (ESCdMs).
Ex vivo AMs obtained from calf bronchoalveolar lavage (BAL) fluid were
analysed extensively so that the in vitro ESCdMs could be compared to them. Flow cytometric analysis demonstrated that BAL cells differentially expressed
the scavenger receptor, CD163, and high CD163 expression corresponded
with increased expression levels of other macrophage molecules compared to
the CD163- subset. The BAL cells were shown to have uniformly high
expression levels of CD172a, ADGRE1, CD206, and CD14, whilst there were
lower levels of CD80, MHC II, CD1b, CD40 and CX3CR1. Analysis of BAL
cells by single cell RNA sequencing (scRNASeq) showed that subsets of AMs
exist which express genes involved in the cell cycle, antigen presentation, the
inflammatory response, and host defence. The analysis of bovine BAL cells by
both flow cytometry and scRNASeq indicated that subsets of macrophages
exist within the lung which may have differences in ontogeny, microbial
exposure history, lung localisation, or function.
Bovine ESCs provide unlimited, experimentally tractable macrophages
when put through a three-phase differentiation protocol which involves
mesoderm induction, myeloid lineage commitment and macrophage
maturation. RT-qPCR analysis confirmed that pluripotency gene expression
decreased and macrophage gene expression increased during the
differentiation process, and RNASeq analysis demonstrated that ESCdMs and
BAL cells expressed many of the same macrophage genes. Flow cytometric
analysis indicated that bovine ESCdMs had high cell-surface levels of
molecules involved in pathogen recognition and antigen presentation including
CD206, CD163, CD14, MHC II, CD80, CD86, and CD1b. However, there was
very low expression of CD172a and ADGRE1, which were highly expressed
on the bovine BAL cells. The ESCdMs had functional similarities to BAL cells
as both cell types were capable of phagocytosing fluorescent particles and
both increased cytokine gene expression when exposed to lipopolysaccharide
(LPS).
The IL10 gene encodes an important immunosuppressive cytokine
which can be upregulated by M. bovis to enhance infection. Therefore, bovine
ESC clones carrying a deletion in the IL10 gene were generated by
CRISPR/Cas9 gene editing. These mutant ESCs were then differentiated into
macrophages which were deficient in IL-10 to examine the impact of this
cytokine in M. bovis- infected macrophages. Flow cytometric analysis of M.
bovis-infected BAL cells, wild type ESCdMs, and IL10 knockout ESCdMs
demonstrated that CD80, CD206, and CD40 expression increased during
infection. However, differences between BAL cells and ESCdMs were also
observed, and possible roles for IL-10 were identified. The presence of
mycobacteria within the ESCdMs was visualised using rhodamine B-stained
M. bovis. This showed that by 1 hour post infection most ESCdMs were free
of M. bovis, but a small proportion of ESCdMs were more heavily infected and
appeared to be in the process of dying.
The work presented in this thesis demonstrated that bovine ESCdMs
can be generated and they are comparable to ex vivo macrophages. The use
of the ESCdMs as a tool to model M. bovis infection should provide further
insights into macrophage-mycobacteria interactions and identify targets for
intervention
Landscapes of anxiety between the cave and the oil palm trees: local legitimation in East Kalimantan
No full textThis thesis examines the intersection between international environmental governance initiatives for social forestry, smallholder palm oil cultivation, local struggles for land access, and the politics of indigeneity and citizenship in a changing Indonesian political economy. It uses a combination of discourse analysis and ethnography, guided by theoretical lenses of assemblage thinking and institutional bricolage, to interrogate two distinct types of land legitimation struggle practiced by members of Merabu village, located in the Berau District in East Kalimantan; one for social forestry and one for smallholder palm oil cultivation. It considers how land legitimation practices occur in contexts of the institutional pluralism and ambiguity in ways that aim to render some land claimants and their claims legitimate, allowable, and/or legal, and others not. Summary of findings suggest that practices of local land legitimation in Merabu involve productions of collective identity, social relations, and technologies of recognition in ways that render some actors, interests, and land claims legitimate and others subaltern, representing potential issues of injustice and alienation occurring through environmental governance practice. Villager strategies for repurposing assets and powers from one land rights context to another in attempts to render legally ambiguous claims legitimate reflect everyday struggles for citizenship in a democratizing Indonesia. This raises critical questions for how land rights, legality, and political subjectivity may be better understood within the contexts of environmental governance and Indonesian democracy in regards to the pursuit of justice.
Analysis is guided by three core research questions:
1)How are contemporary local land struggles contextualized within neo-colonial histories of racialized socio-spatial control and their contestation?
2)How do environmental governance projects shape some local subjectivities, interests, and land use practices as legitimate and others illegitimate?
3)In what ways are denials of legitimacy contested and resisted by local land claimants in the pursuit of their interests and political inclusion?
Following conceptual frameworks introduced in Chapter 2, and case study context in Chapter 3, I address these questions in my empirical chapters. To answer the first question, in Chapter 4, I conduct a deliberative discourse analysis on land policy texts and their political/historical contexts to trace how contestations over authoritative ways of conceptualizing land legitimacy shape productions of forest dwelling subjectivities as legitimate or illegitimate vis-à-vis land rights and political participation. Findings show that histories of contestation between multiple policy storylines of land legitimation affect systematic forms of alienation and subalternity for forest dwelling people, like the Lebbo. These alienations shape struggles for legitimation in contemporary contexts of environmental governance, wherein pluralist authoritative institutions and discourses of rights recognition interpellate forest-dwelling subjectivities in ambiguous and problematic ways.
I answer the second question in Chapter 5, where I conduct ethnographic fieldwork in Berau over the course of 12 months in 2015-2016 to examine how the Berau Forest Carbon Project (BFCP), a subnational REDD+ demonstration project, worked to territorialize Merabu subjects and spaces within the REDD+ environmental governance assemblage at the project’s early stage. Findings suggest that essentializations of villager identities and interests draw on tropes of indigeneity while simultaneously denying formal indigenous rights or self-determination. Subject productions as such, combined with facilitation of capacities for legibility by State authorities, render villagers and their land claims to their ancestral forest legitimate insofar as they adhere to what Li calls the “non-market slot” (2014).
I answer the third question in Chapter 6, where I draw on key-informant interviews collected during fieldwork in 2022, at the end of the BFCP project cycle, to examine villagers’ efforts to legitimate land claims for smallholder palm oil cultivation, i.e. outside the “non-market slot”. Here, I observe villagers repurpose technologies of legitimation gained through their participation in the BFCP for deployment in other contested legitimation claims with district government authorities in order to render themselves and the claims legitimate in what would otherwise be considered a restricted form of land use, in what I characterize as acts of bricolage. Here, I draw on insights from previous chapters and critical scholarship on citizenship in post-colonial Indonesia to argue that such legitimation practices in legally ambiguous contexts represent vital struggles for everyday citizenship amidst the incomplete project of Indonesian democratization.
I my summation, I reflect on the fluid, reflexive relationship between indigeneity and citizenship in the Indonesian context in relation to the political ambitions of historically marginalized people in pursuit of autonomy, survival, and development
Thomas Jefferson’s special relationship: England and the Anglo-Virginian, 1743-1826
Get PDFThis thesis explores the special relationship of Thomas Jefferson with England through his life and public career. The first English authored biography of Thomas Jefferson observed that for the first thirty-three years of his life Thomas Jefferson was a British subject and ‘Britain has at least a share in him.’ It was more of an English than British share. This thesis measures that English aspect of Jefferson, how it mattered, how long it lasted, and how it eroded. It can be termed Anglicisation and de-Anglicisation. For all the Francophilia accusations levelled against Jefferson by Federalist opponents it was England and Britain that most defined Jefferson’s world, from his upbringing in colonial Virginia to his retirement years at Monticello. Jefferson was Janus-faced, and arguably sphinx-like, regarding England. He could look admiringly and emulate whilst critiquing and resenting its enduring influence on him politically, culturally, and personally. This thesis employs a chronological structure, synthesising multiple sources, studies, and types of history. The main argument can be summarised as ‘No Anglicisation, no Jefferson.’
This thesis challenges the narrative of ‘Jefferson the Anglophobe.’ It is used mostly as shorthand for Jefferson’s hostility to British Government policy but misleads in its scope and meaning as an irrational dislike of England and the English. The term is remarkably prevalent yet markedly unhelpful to understanding how important England was to Jefferson. References to Jefferson’s Anglophobia need greater caution or at least major caveating. This thesis makes the case for nuance and precision. Related to this and more minorly is the nature of Jefferson’s Francophilia and its overstatement in depth and duration. Jefferson admired and supported France in many ways, but it was conditional, contextual, and compatible with his Anglo-Virginian background and politics.
Thirdly, this thesis makes a significant contribution to our understanding of Jefferson and the history of the American Revolution and Early Republic. This is the argument that Anglicisation made not just the revolution but the early republic too, including Jefferson. Jefferson was the Anglo-Virginian republican cut from the cloth of English seventeenth century republicanism, combining radicalism and conservatism of a particular kind. This thesis contributes to Early Republic history through focus on Jefferson as the synecdochal American Founder and Anglo-Virginian, bridging the gap between pre-revolution Anglicisation and 1820s continuing Anglophilia histories.
Jefferson’s separation from England and Great Britain, his de-Anglicisation and identification as American, was multi-layered, ebbing and flowing, varying between the private and public spheres that Jefferson used to order his life. Any view of a fully de-Anglicised Jefferson by 1783, 1789 or 1826 is untenable, demanding a more nuanced understanding of his oft conflicted relationship with England, Englishness, and Britain. The relationship was not singular, Manichean or binary. It was complicated. It was certainly significant, enduring, and special
Lagrangian cobordisms and Chow groups: dimensionality and computations
No full textThis thesis studies Lagrangian cobordisms and tropical Chow groups from two
different perspectives.
On one hand, we have a finite-dimensional setting where we are able to do explicit
computations and exhibit several isomorphisms. On the symplectic side, we
consider symplectic 4-manifolds called symplectic bielliptic surfaces and present
a detailed computation of a Lagrangian cobordism group generated by tropical
Lagrangians equipped with several decorations. Using this computation and Homological
Mirror Symmetry, we show that this Lagrangian cobordism group maps
isomorphically to the Grothendieck group of the Fukaya category of the bielliptic
surface. On the tropical side, we compute the tropical Chow group of a tropical
Klein bottle. We put both results together by showing that there is a geometric
isomorphism from the tropical Chow group of a Klein bottle to the Lagrangian
cobordism group of the associated symplectic bielliptic surface.
On the other hand, we have an infinite-dimensional setting where, despite
computations not being possible, we are able to prove structural results. We first
prove such infinite-dimensionality: the symplectic version is a minor extension of
results of Sheridan-Smith, whereas the tropical version is a novel result. We then
consider symplectic tori that arise as Lagrangian torus fibrations over polarised
tropical affine tori. We show that their Lagrangian cobordism group, despite
infinite-dimensional, admits a natural geometric filtration of finite length. We
develop a theory of Fourier transforms between Fukaya categories of dual symplectic
tori and use it to prove that our filtration is mirror to Bloch’s filtration
on the Chow group of points of the mirror abelian variety
Examining and extending Bayesian theories of autism
Get PDFRecent approaches to understanding autism view it through the lens of the Bayesian brain framework. Within this framework, it is hypothesized that beliefs about the world are represented probabilistically in the brain and are updated using Bayesian statistics. Perception is understood a process of inferring the most likely cause of sensory input by combining sensory information with prior beliefs about the environment. Bayesian theories of autism propose that its heterogeneous symptomatology arises from an imbalance in the weighting or ‘precision’ of priors and likelihoods, favouring the latter. While this is a promising approach, the relevant research is highly diverse, occasionally resulting in contradictory findings, with some studies finding no evidence of such imbalances in autism and others showing more nuanced and complex results.
The aim of this work is twofold. First, we conducted a comprehensive examination of previous research, starting by conducting a systematic review of Bayesian studies of autism and autistic traits. The results were mixed, with a slight majority of studies finding no difference in the integration of Bayesian priors and likelihoods. Methodologically, many studies had low statistical power and inconsistent approaches. In a subsequent paper, we clarified the meaning of ‘sensory precision’, a central term in Bayesian theories of autism. Using a simple Bayesian perception model, we examined the role of two possible interpretations in the inferential process and their relevance to autism theories. We reanalysed data from an old study under this new light.
The second part of this work expands upon the main Bayesian theories of autism to better approximate the behaviours of autistic individuals. Informed by the literature review, we designed an experiment to compare implicit and explicit learning across autistic traits, manipulating the presence and content of instructions across conditions. We found that the presence of instructions exerted a significant influence on participant priors until the end of the task, while the effect of their content had only a weak, temporary influence. Our results showed no relationship between autistic traits and response biases, but offered hints of a weak correlation between autistic traits and participant uncertainty about implicit environmental regularities. In another study, we applied the circular inference model, a model of belief overconfidence, to autistic traits. Our findings did not reveal any significant differences in circularity across the autism spectrum. To further explore this model in a more autism-relevant context, we designed a follow-up task that incorporated social elements. Surprisingly, the pilot results indicated that participants did not engage in Bayesian inference, instead they simply averaged the information obtained from different sources.
These results show that, while imbalance theories of autism are prominent within the field, their simplest form is weakly supported by experimental evidence. Both the literature review and our study on implicit and explicit learning highlighted the need for more nuanced approaches that focus on prior development. We discuss two such theories of volatility processing impairments in autism, which imply higher uncertainty in strong autistic traits, as hinted by our experimental findings. We also discuss methodological issues commonly present in the field and the need for thorough computational modelling
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