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Phase changes on ultra-smooth surfaces
No full textThe evaporation phase change of droplets is a complex and varied phenomenon in both
nature and in real world scenarios. The phase change can take many forms based on the
liquids involved, the surfaces they interact with and the vapour phases into which they evaporate.
This places the interest in droplet evaporation in many varied areas from; inkjet printing
and microfluidics, to virology and biofouling. Understanding the dynamics that drive and
control the evaporation of droplets allows for increased understanding and control over their
behaviour. By understanding how complex fluids as well as simple pure liquids behave, allows
for more complex systems to interact with fluids without the fear of scaling and fouling.
In recent years, ’smooth’ and ’ultra-smooth’ surfaces have become popular in literature for their
ability to achieve ideal contact modes of evaporation and incredibly consistent and repeatable
liquid interactions. The use of grafted polymer surfaces such as Slippery Omniphobic Covalently
Attached Liquid like surfaces (SOCAL) and lubricated surfaces such as Slippery Liquid
Infused Porous Surfaces (SLIPS) has allowed for Constant Contact Angle (CCA) evaporation
modes to be achieved. Despite the proposal of ideal evaporation modes in the 70’s, it took
many more years for the surface manufacturing to be able to overcome the contact line pinning
to achieve these ideal evaporation modes. With the advent of this capability, surfaces capable
of droplet shedding and reduced scaling are now possible. Whilst these ’smooth’ surfaces
are being successfully created by more research groups worldwide now, their behaviour with
complex and non-pure liquids is still relatively unknown especially in predicting how they
will evaporate. As these smooth surfaces allowed for a leap in knowledge for pure liquid
and notably water phase change phenomena, it stands to be seen that they offer a unique
opportunity to advance our understanding on the phase changes of more complex fluids.
This thesis shows how to repeatably and reliably produce surfaces which can be classified
as ’smooth’ due to their low contact angle hysteresis values (CAH). It shows a method for
how to calculate these hysteresis values accurately with low errors on surfaces with <2◦ CAH.
These surfaces are then shown to achieve an ideal CCA evaporation mode on solid surfaces,
utilising the low hysteresis properties of these surfaces to overcome contact line pinning. The
work displayed in this thesis also details the manufacturing of biomimetic respiratory fluid
used to simulate the droplets that humans respire. It also details the interaction between
these biomimetic respiratory droplets and the low hysteresis SOCAL surfaces to observe the
complex evaporation dynamics, complex structures formed and how these surfaces could
potentially be utilised for antifouling and antiscaling.
This thesis also shows the ideal evaporation of NaCl salt droplets on SOCAL, detailing the
evaporation dynamics. It shows the mitigation of crystal nucleation in order to halt the evaporation
of the salt droplets, through the utilisation of the droplet’s water activity below 75%
relative humidity (Rh) for the first time. This thesis then details the development of the diffusion
limited evaporation equation, modified to improve accuracy and use with more complex fluids.
This theoretical development takes into account the partial vapour pressures surrounding the
evaporation sessile droplet in the form of a water activity factor. This is utilised alongside a
non-isothermal modelling of the diffuse evaporation to reduce the number of assumptions
used when modelling the evaporation of droplets on solid surfaces and improve the accuracy.
This thesis then works towards improving our understanding of why droplets will stop evaporating
under certain conditions. It also aims to better understand the mechanisms behind
mitigating the crystal nucleation by comparing the ’ultra-smooth’ SOCAL surfaces, with novel
made Table Top SLIPS surfaces for the evaporation of NaCl salt droplets.
The work then displays how the geometry of the wetting ridge formed by a droplet on a lubricated surface,
can then be utilised to analyse droplets that typical goniometry cannot
On the topology in end-to-end automatic speech recognition based on differentiable weighted finite-state transducer
Get PDFTraditionally, Automatic Speech Recognition (ASR) systems have been based on Hidden Markov Models (HMMs) combined with Gaussian Mixture Models (GMMs) and Deep Neural Networks (DNNs).
The topology, or structure, of the HMM defines how the states are connected, how transitions are made, and how speech feature vectors align with output symbols.
Since the 1980s, many discussions and experiments have refined HMM topologies, leading to the widespread adoption of the left-to-right Bakis topology. However, the topology of end-to-end ASR systems has not been studied as extensively.
End-to-end (E2E) ASR methods allow us to train a neural network (NN) model from scratch with transcribed data only, which simplifies the training pipeline compared to traditionally HMM-based method.
Connectionist Temporal Classification (CTC) is a popular E2E ASR method known for its one-state topology, where each state represents a specific output symbol.
Despite its popularity, the unique topology of CTC is often applied without much consideration.
This thesis investigates the role of topology in E2E ASR systems, especially in a framework based on Differentiable Weighted Finite-State Transducer (DWFST).
We start from an attempt of modifying the topology of CTC, which results in a new loss function, named MMI-CTC. Our findings show that MMI-CTC improves overall recognition accuracy, in terms of Word Error Rate (WER), and convergence speed, demonstrating the importance of topology in end-to-end ASR systems and its impact on the training process.
Building on the established importance of topology, we explore its role further in end-to-end ASR.
The common CTC implementation, based on the forward-backward algorithm, is inflexible and difficult to modify, as creating a new algorithm for each topology is time-consuming and error-prone.
To overcome this, we introduce an end-to-end ASR framework based on DWFST.
This framework replaces the forward-backward algorithm, providing a flexible and general platform for experimenting with various topologies.
With the DWFST-based framework, we first explore how topology affects recognition accuracy at different output frame rates.
We discover that various topologies perform differently depending on the output frame rate.
The topology influences the number of possible alignments between the input and target sequences.
By adjusting the topology, we can control these alignments and improve the model's overall accuracy.
Besides, we address how different topologies impact alignment quality, particularly the ``peaky'' issue associated with CTC. Our study shows that modifying the topology can significantly improve alignment quality without affecting WER performance. This improvement benefits various downstream tasks and highlights the advantages of our proposed topological changes.
We also examine if the topology impacts the decoding accuracy of the Viterbi decoder.
During training, all possible alignments are considered, but during decoding, the Viterbi decoder only looks for the most likely alignment.
We would like to see if there is a dominant path in the decoding space that explains why the Viterbi decoder works well.
Our research shows that there is no single dominant path, but the Viterbi decoder still performs accurately under certain conditions, which we discuss in this thesis in depth.
Additionally, we investigate whether the choice of topology affects the model's generalisability—its ability to perform well on different datasets even only trained on one dataset.
We believe that topology impacts how speech features align with output symbols, thus influencing the acoustic modelling power.
Our findings reveal that different topologies lead to varying levels of generalizability, mainly affecting the acoustic model, even though the internal language model (ILM) is relatively weak in our settings.
In terms of the ILM, we also explore its existence in CTC-based E2E ASR systems, a topic with mixed opinions among researchers.
We design a procedure to verify the existence of ILMs in these systems and find no evidence that a strong ILM exists in a pure CTC-based ASR system.
In summary, this thesis demonstrates that topology is a crucial factor in end-to-end ASR systems, and its impact on the training process, the convergence speed, the recognition accuracy, the generalisability, and the alignment quality should not be underestimated
Police encounters with people with mental illness: achieving epistemic and procedural justice
Get PDFPolice encounters with people with mental illness (PMI) continues to be a highly studied topic in the United States. A deinstitutionalization movement combined with poor funding for community resources and stricter commitment laws made these encounters much more prevalent. Concerns such as excessive force, over arrest, and roadblocks to treatment have largely been the focus of prior research. A noteworthy gap in literature is research from the perspective of PMI. PMI are a stigmatized and marginalized community, which has resulted in their voices being ignored. This study sought knowledge directly from PMI in order to fulfil this gap while comparing PMI perceptions with those of police. Two focus groups were conducted in Dane County, Wisconsin: one involving Dane County PMI who have experienced police encounters and one involving officers from a municipal police department in Dane County. Informed by epistemic and procedural justice theories, this investigation sought to determine the role of stigma, PMI agency, police’s ability to recognize and address PMI’s concerns, what changes are needed for improvement, and how PMI’s perceptions compare with police’s perceptions. Findings indicate these encounters are significant and potentially life-altering events involving both traumatizing and positive experiences. Officers who are patient, empathetic, and respectful are often associated with positive experiences while negative experiences involve stigma, criminalization, and power imbalances. Meanwhile, police are conflicted over whose responsibility mental health calls should be and how to define success with these calls. Furthermore, officers seem unable to adequately identify mental illness in the field and believe processing someone through the criminal justice system is easier than navigating the mental health system. Both groups agree better community resources and the involvement of non-police personnel, such as social workers, are needed. Better mental health training and education for police along with structured follow up care for PMI are also considered important for improvement. These findings suggest a larger investment into serving PMI in the community is needed, along with concerted efforts to combat mental health stigma
Design, synthesis and biological evaluation of novel intracellular modulators attenuating CCR5 signaling
No full textThe chemokinereceptor CCR5 is implicated in a variety of diseases, including HIV, cancerproliferation and metastasis, inflammatory diseases, and acutegraft-versus-host disease, posing significant challenges in medical researchand therapy. While CCR5 is a well-established target, particularly in thecontext of HIV, research has predominantly focused on its extracellular side.This thesis explores the intracellular allosteric binding site (IABS) of CCR5,a recently identified and promising druggable site for receptor inhibition.
The centralaim of this PhD project is to design and synthesize allosteric intracellularantagonists that can modulate CCR5 signaling and influence downstream eventsresulting from CCR5 activation. Preliminary screening identified a hitstructure with high potential, leading to several rounds of rational drugdesign and structure optimization of disubstituted [1,2,5]oxadiazolo-[3,4-b]pyrazines,aiming for low micromolar IC50s for CCR5. Selectivity against CCR2,the protein most closely related to CCR5, was also tested. Molecular dynamicssimulations and a competition assay with a Gαq11 mimetic confirmedthe intracellular binding mode of these compounds, and mass spectrometrystudies assessed their solubility in a physiological context.
Furtherstructure optimization emphasized the importance of specific regions of thedisubstituted [1,2,5]oxadiazolo-[3,4-b]pyrazines and their crucialhydrogen bonding interactions within the intracellular pocket. Subsequentbiological evaluations such as proliferation and wound healing assays wereconducted to assess the impact of these compounds on CCR5-induced chemotaxis inselected cell lines.
This thesis concludes by summarizing the keyfindings and discussing future prospects and challenges, highlighting thepotential scientific implications and proposing directions for furtherexploration of intracellular CCR5 modulators' therapeutic potential
Perinatal and offspring outcomes of maternal epilepsy
No full textBACKGROUND:
Epilepsy during pregnancy is associated with increased odds of miscarriage, stillbirth, preterm birth, maternal mortality, offspring congenital conditions, neonatal intensive care unit admission, neonatal or infant death, and offspring neurodevelopmental disorders. Findings vary between countries and study design, and although prenatal anti-seizure medication (ASM) exposure exacerbates adverse outcomes, there is evidence of increased risk without exposure. Furthermore, prenatal ASM prescribing is increasing, and there is limited population-based data specific to the United Kingdom (UK), emphasising the need to address the priorities outlined by the UK Epilepsy Priority Setting Partnership regarding epilepsy in pregnancy and prenatal exposure to ASM. This thesis aims to investigate the association between maternal epilepsy and 1) perinatal (maternal, foetal, and neonatal) outcomes, 2) offspring (neurodevelopmental, educational, and adulthood socioeconomic) outcomes, and 3) conduct an exploration of the role of prenatal ASM exposure.
METHODS:
Two systematic reviews and meta-analyses of observational studies were conducted concerning 1) perinatal outcomes in Chapter Two and 2) offspring outcomes of maternal epilepsy in Chapter Three. These reviews provided unadjusted pooled odds ratios (OR) with 95% confidence intervals (95CI) and highlighted knowledge gaps. A retrospective cohort study was then conducted to investigate the adulthood socioeconomic outcomes in children with and without a history of seizures. This study used regional Scottish data, and while the results are not provided in this abstract, the manuscript is provided in Chapter Four to show the academic and professional developmental throughout this PhD, including applying to regulatory and ethical bodies for data access, and conducting data manipulation and analysis within a Safe Haven setting using relevant statistical software packages. This study provided the technical experience required to conduct a population-based retrospective cohort study using linked routinely collected health data in Scotland (1992-2021) to determine the association between epilepsy in pregnancy and perinatal outcomes and the role of prenatal ASM exposure Chapter Five. The population was identified as all women with at least one pregnancy occurring 1992-2021 in Scotland (1992-2008). Epilepsy was identified using International Classification of Disease codes 9-10. ASM exposure was defined as medications dispensed within the prenatal period. Multi-level multiple binary logistic regressions were conducted to account for covariates and repeated measures; OR and adjusted OR (aOR) with 95CI are provided for perinatal (maternal, foetal, neonatal) outcomes in women with and without epilepsy and all pregnancies with and without prenatal ASM exposure.
RESULTS:
The two systematic reviews found that maternal epilepsy is associated with increased odds of miscarriage OR 1.62 (95CI 1.15, 2.29), stillbirth 1.37 (1.29, 1.47), preterm birth 1.41 (1.32, 1.51), maternal death 5.00 (1.38, 18.04), offspring congenital conditions 1.88 (1.66, 2.12), neonatal intensive care unit admission 1.99 (1.58, 2.51), neonatal or infant death 1.87 (1.56, 2.24), autism 1.67 (1.54, 1.82), attention-deficit/hyperactivity disorder 1.59 (1.44, 1.76), intellectual disability 2.37 (2.13, 2.65), and having special educational needs 2.60 (1.07, 6.34). The odds of adverse perinatal and offspring outcomes were higher with greater use of ASM, yet analyses were not possible for individual ASMs or potential confounders. In national health data analyses, 931,072 pregnancies occurred 1992-2008 (women with epilepsy (WWE)= 2,014 and women without epilepsy (WWoE)= 929,058) and 629,200 occurred 2009-2021 (WWE=2,022, WWoE=627,178; all pregnancies exposed=4,406 and unexposed to prenatal ASM=624,794). Between 1992-2008, WWE had increased odds of preterm birth 1.48 [1.26, 1.74], induced labour 1.42 [1.28, 1.57], caesarean section 1.34 [1.19, 1.51], eclampsia 11.96 [6.32, 22.61], preeclampsia 1.55 [1.22, 1.98], PPH 1.29 [1.13, 1.47], maternal death 6.47 [2.40, 17.40], offspring neonatal intensive care unit admission 1.84 [1.59, 2.12], offspring congenital conditions 1.60 [1.33, 1.94], low birth weight 1.58 [1.35, 1.86], and Apgar <7 1.54 [1.24, 1.92]. When additionally adjusting for prenatal ASM and other covariates in pregnancies occurring 2009-2021, WWE had increased odds of induced labour aOR 1.17 [1.02, 1.34], and no differences were observed for other outcomes. In all pregnancies occurring 2009-2021, those exposed had increased odds of preterm birth aOR 1.47 [1.25, 1.74], induced labour 1.38 [1.25, 1.52], caesarean section 1.14 [1.01, 1.27], offspring congenital conditions 1.34 [1.04, 1.73], neonatal intensive care unit admission 1.54 [1.33, 1.78], neonatal death 2.53 [1.16, 5.53], and low birth weight 1.41 1.47 [1.23, 1.75].
CONCLUSION:
Systematic review and meta-analysis findings indicated that women with epilepsy had increased odds of adverse perinatal and offspring outcomes, and that odds of adverse outcomes are exacerbated by ASM burden. National data studies provide further evidence, suggesting that, although epilepsy is independently associated with increased odds of induced labour, prenatal ASM exposure independently contributes to increased odds of other adverse perinatal outcomes. Comprehensive care from an epilepsy specialist is required, considering both the condition and the potential role of ASMs. Furthermore, the results highlight the need to counsel WWoE who are taking ASMs during the prenatal period, as there is evidence that the risks of adverse outcomes are increased, regardless of epilepsy diagnosis
Exploring associations between maternal smartphone use and mother-infant synchrony from a dynamic systems perspective
Get PDFDyadic behavioural synchrony is one of a number of complex bidirectional processes that take place within interactions between a mother and her infant. In the first year of life, when an infant is still prelinguistic, processes such as dyadic synchrony are used to enable the dyad to communicate with each other through shared behaviour and affect, including mutual gaze and touch, facial affect, and vocal intonations. Dyadic synchrony has been observed to emerge in infants as young as 3 months old, typically developing further between 3–9 months old. Dyadic synchrony is a bidirectional process, requiring reciprocal communication from both partners. As such, breakdowns in synchrony, from either infant or mother, can have implications for the development of a positive relationship.
Such breakdowns have been suggested to occur when mothers habitually use their smartphones in the presence of their child. Studies have found that mothers with children aged 0–5 years old who frequently use their phones, may demonstrate less maternal sensitivity and are less likely to respond to their child’s bids for attention than mothers who use their phones less often. This phenomenon of unresponsiveness to proximal relationships has been termed ‘technoference’ a concept describing interruptions to everyday interactions due to the use of digital technology. Crucially, while some recent quantitative research has shown that caregiver smartphone use may have an impact on both infants’ cognitive and social-emotional development, very little evidence is currently available regarding the impacts of parental smartphone use on infants under 12 months old.
This thesis explores the impacts of maternal smartphone use on mother-infant dyadic synchrony when the infant is aged between 3–9 months old. Specifically, the objectives of this thesis are to i) synthesise known risk and protective factors that may influence dyadic synchrony in this age range; ii) evaluate the potential additional risk posed by maternal smartphone use on mother-infant interaction processes; and iii) explore the impact maternal smartphone use has on dyadic synchrony within the mother-infant dyad. To fulfil the thesis objectives, three studies were undertaken.
The first study was a systematic review synthesising risk and protective factors for dyadic synchrony in mother-infant dyads where the infant was aged between 3–9 months old. In total, 28 studies were included in the review. Systematic evaluation highlighted four main areas of influence on dyadic synchrony: i) infant demographics; ii) physiological factors; iii) maternal mental health; and iv) miscellaneous factors such as the immigrant experience, maternal playful singing, and the mother’s perception of being parented herself. Results suggest that social determinants of health, underpinned by biological factors, are likely to influence the development of dyadic behavioural synchrony in mothers and their infants aged 3–9 months old.
The second study explored associations between risk and protective factors for dyadic synchrony in mothers and their infants aged 3–9 months old, as well as the addition of maternal smartphone use as a potential additional risk factor. A cross-sectional survey design was employed, recruiting 450 mothers from across the UK. As dyadic synchrony is a complex behavioural process and difficult to capture through static self-report measures, an outcome variable of mother-infant responsiveness was used to proxy behavioural synchrony within the dyad. Data from this cross-sectional survey was used in two forms of analysis, as outlined below.
Analysis 1 employed hierarchical multiple linear regression to explore the interactions between predictor and outcome variables. The results of this analysis suggested that the likelihood of the mother using her smartphone in the presence of her infant was negatively associated with mother-infant responsiveness. This association, however, was observed only in specific parenting domains, specifically during daily hygiene practices such as getting the baby ready for the day, bathtime, or nappy changes. Due to the cross-sectional nature of the study, no directionality can be assumed, however a relationship between lower mother-infant responsiveness and likelihood of using a smartphone during sensitive parenting practices suggests that maternal support, including education focusing on navigating infant care and smartphone use is needed in the perinatal stage.
Analysis 2 used a person-centered cluster analysis to explore the psychological risk profiles of mother-infant dyads to further understand their support needs. The results of this analysis identified three clusters of mothers with unique psychological profiles.
Cluster 1 comprised mothers who self-reported high infant social emotional development concerns, high likelihood of maternal smartphone use, and low mother-infant responsiveness. Cluster 2 comprised mothers who self-reported high maternal depressive, anxiety, and stress symptoms, low social support, high likelihood of maternal smartphone use, and low mother-infant responsiveness. Importantly, no significant differences were found in the self-reports of mothers in Cluster 1 and 2 in their levels of perceived mother-infant responsiveness, nor in their likelihood of using their device in the presence of their infant. Cluster 3 represented almost 50% of the sample and displayed a low risk profile, with mothers self-reporting high levels of mother-infant responsiveness, low likelihood of smartphone use, high maternal wellbeing and social support, low depressive, anxiety, and stress symptoms, and low levels of perceived infant social emotional difficulties. Cluster 1 and 2 both reported significantly higher smartphone use and significantly lower mother-infant responsiveness than the low-risk Cluster 3. As the risk profiles of Clusters 1 and 2 were uniquely different, this suggests that both perceived infant social emotional developmental issues (as seen in Cluster 1) as well as poor maternal mental health (as seen in Cluster 2), are associated with a higher likelihood of smartphone use, as well as lower mother-infant responsiveness. These results, taken as a whole, suggest that mother-infant dyads whose risk profiles contain either maternal or infant mental health difficulties are at heightened risk for problematic smartphone use and support should be tailored to individual dyads’ mental health needs.
The final study of this thesis utilised a modified experimental paradigm called the Still-Face Paradigm (SFP) to explore how maternal smartphone use may impact mother-infant dyadic synchrony in infants aged between 3–6 months old. Experimental conditions during the modified still face (SF) phases comprised of the mother using the smartphone for both i) audio call and ii) text conversation, while not interacting with her infant. Both mother and infant’s affective behaviours were coded in the initial free play (FP) phase as well as reunion (RU) phases following the period of smartphone use. A dynamic systems approach to measurement was employed to capture both mother and infant’s behaviour, as well as the behaviour of the dyad as a single system. Two outcome variables were reported comprising i) flexibility and ii) synchronous negative affect. The results of this study suggest that flexibility within
the dyad was significantly higher in RU phases compared to the FP phase, indicating that the mother and infant recognised the interruption caused by the smartphone use as a stressful event and therefore needed to employ a wider range of behavioural strategies to co-regulate their proceeding interaction. In terms of synchronous negative affect, a significant difference was observed between all three conditions, with both RU phases reporting higher synchronous negative affect than the FP phase, and further RU after texting reporting higher synchronous negative affect than RU after audio call. These results suggest that both mother and infant were significantly more likely to employ negative behavioural affective strategies simultaneously after an interruption of smartphone use, with even more instances of synchronous negative affect after the mother used the phone to text compared to taking an audio phone call. Such synchronous negative affect may be the result of the mother using co-regulation strategies to join the baby in their distress, validating their response to the stressful event. It may also signify that after texting, co-regulation becomes more difficult, with mothers potentially finding it harder to join the baby and becoming emotionally overstimulated themselves by the increase in negative affect within the dyad.
Across the thesis’ studies, social determinants of health, coupled with biological factors, were identified as risk factors for both development of dyadic synchrony as well as for heightened problematic smartphone use. Further, the modality of maternal smartphone use may have implications for the development of interactions within the dyad. The key findings in this study point to the need for increased education support, at a population level, and during the perinatal period to enhance mothers’ understanding of smartphone use as a potential risk to the developing relationship with their infant. Future research should be directed towards more naturalistic empirical studies, capturing how and why mothers use their phones in their daily life. Further, longitudinal studies should be employed to understand the long-term influences that maternal smartphone use may have on the development of relational processes between mother and infant. In addition to widened quantitative studies, qualitative research working in partnership with mothers should be carried out to understand the education and support needs of mothers with young infants in this age range
The evolutionary ecology of vector-parasite interactions
Get PDFEcological interactions between parasites and their within-host environment and within-vector environment (in the case of vector-borne diseases) shape the severity and transmission of infections. Therefore, applying evolutionary ecology frameworks to explain how and why parasites respond to environmental variation is becoming increasingly more common. A greater understanding of within-host and within-vector ecology can improve predictions of parasite evolution in response to disease control interventions and other environmental changes. Malaria is the deadliest vector-borne disease and is caused by parasites of the Plasmodium genus which are transmitted between vertebrate hosts via mosquitoes (often Anopheles spp.). However, despite its public health importance and decades of intensive research, fundamental aspects of malaria transmission remain poorly understood. In particular, the sources of variation in parasite life history traits that shape within-vector development and onward transmission to a new vertebrate host have received little attention.
By integrating evolutionary ecology, parasitology and vector biology, I investigate how environmentally determined variation in vector traits shapes parasite traits expressed within the vector, and the subsequent implications for between-host transmission and parasite evolutionary potential. It is becoming increasingly important to understand how parasites evolve to cope with the challenges and/or exploit the opportunities provided by their within-vector environment, because vector control tools are altering vector genotypes and phenotypes. Therefore, I firstly created a framework using evolutionary ecology to predict how parasites could evolve in response to vector control tool-imposed changes in their vectors, collating the consequences of these changes into overarching agents of selection acting on parasites (Chapter 2). Following this, I focussed on the following key aspects that arose, examining: (i) whether genetic variation within parasite populations influences the potential for selection to act on fitness-related traits (Chapter 3), (ii) the extent of plasticity for parasite traits that are altered in response to novel within-vector environments (Chapter 4), (iii) how changes to vector biology as a consequence of vector control directly and/or indirectly affect parasite fitness (Chapter 5), and (iv) if parasite transmission potential and fitness can be better estimated (Chapter 6).
My empirical results reveal that there are strain-specific differences in within-vector parasite traits important for transmission (Chapter 3), suggesting that there is underlying genetic variation for natural selection to act upon. In addition, I show that both parasite (Chapter 4) and vector traits (Chapter 5) exhibit plastic strategies in response to variation in the availability of nutritional resources. My findings (Chapter 4) suggest that while parasites are constrained by limited access to nutritional resources, they will actively adjust their within-vector development to best exploit the resources available in ways that maximise transmission. I also demonstrate (Chapter 5) that the timing and propensity of vector biting is dependent on their nutritional state; while parasites produce fewer progeny in starved mosquitoes, these mosquitoes have a higher propensity to bite, and are also more likely to forage at a non-classical biting time when humans are unprotected by bed nets. Finally, I develop and test a non-destructive assay to track parasite development over time (Chapter 6) and demonstrate that while parasites expelled in mosquito saliva during sugar feeding are detectable, increasing the detection rate is required to maximise the utility of these assays for quantifying transmission dynamics.
Together, my results reveal that malaria parasites demonstrate considerable variation in within-vector traits and can plastically respond to changes in their environment in manners that appear adaptive. Thus, my findings suggest that parasites have the ability to evolve and plastically change fitness-determining traits, many of which are affected by vector control tool use. However, my work also demonstrates that within-vector environmental variation (such as resource availability) can influence the transmission potential of parasites and vectors in opposing ways and may have complex consequences for disease dynamics. Therefore, investigating how and why both vector and parasite phenotypes respond to environmental change is necessary for understanding for how natural selection will shape disease transmission and parasite evolution, especially in response to current and future control interventions
Engineering programmable trans-splicing riboregulators for complex cellular logic computation
No full textSynthetic genetic circuits program the cellular input-output relationships to execute customized functions. However, efforts to scale up these circuits have been hampered by the limited number of reliable regulatory mechanisms with high programmability, performance, predictability, and orthogonality. In this thesis, I engineered a class of Split-intron ENabled Trans-splicing Riboregulators (SENTRs) based on de-novo-designed external guide sequences (EGSs). SENTR libraries provide low leakage expression, wide dynamic range, and low crosstalk at multiple component levels. SENTRs can sense RNA targets, process signals by logic computation, and transduce them into various outputs, either mRNAs or ncRNAs. SENTR represents a powerful and versatile regulatory tool at the post-transcriptional level in Escherichia coli, with broad applications in biotechnology. I subsequently demonstrated that digital logic operation with up to six inputs could be implemented by using multiple orthogonal SENTRs to regulate a single gene simultaneously and coupling SENTRs with split intein-mediated protein trans-splicing. The integration of split introns and inteins is an efficient, genetically compact, and generally applicable strategy for building multi-input processing devices to significantly increase the information processing capacity of a single regulator gene
Trade-offs between desires and jobs: exploring academic freedom in the context of mainland China
No full textAcademic freedom (AF), as a right and responsibility, has been argued as
fundamental to modern universities and essential to scholarly activities. I start from
the position that the Chinese scenario of AF is not simply a Western replica, and it is
not necessary to be a Western replica. This empirical research aimed to explore and
understand the state of AF as experienced and perceived by academic staff in
mainland Chinese universities. The approach adopted was ‘basic qualitative
research’. Thirty-one participants were recruited through purposive sampling
methods. Semi-structured interviews and reflexive thematic analysis were
conducted.
The findings suggest that there was a general pattern of ‘trade-offs’ between
academics’ desire for AF and their job security and/or promotion. Under this pattern,
the predominance of a ‘Publish-or-Perish’ culture (PoP culture) was one major
source of constraints on AF, and the overall coping strategies indicated a sense of
‘playing with the rules’. Political and ideological power (P&I power) was the other
source of constraints, and the overall responses showed a sense of ‘playing it safe’.
Besides, differences in the practice of AF were found between disciplines, kinds of
universities, and individual academics’ backgrounds.
By adopting Isaiah Berlin’s (2002) theory of freedom, Steven Lukes’s (1974; 2005;
2021) theory of power, and Pierre Bourdieu’s (1990; 2010) theory of practice, I
highlight that 1) the meaning of AF in mainland China has some commonalities but
also differences from AF in Western societies, that 2) P&I power could exert its
influence on AF in the forms of observable/overt control, explicit/implicit control of
agendas, and ideological control, and that 3) academics with different ‘symbolic
capital’, ‘agency’, and ‘habitus’ practised their AF under the PoP culture differently.
Finally, this study indicates that AF in mainland China incorporates both politicised
and less/non-politicised meanings. Practical implications are generated for
policymaking, university management, and Chinese academia
Neglected tropical diseases from their origins to today: impacts of policy, funding and the COVID-19 pandemic
Get PDFNeglected Tropical Diseases (NTDs) are a group of 20 bacterial, viral, and parasitic diseases as defined by the World Health Organization that affect approximately a billion of the world’s poorest people, each year. Infection with one or more NTDs serves to keep people locked in poverty through the cost of treatment(s), from loss of productivity, and can result in lifelong symptoms, disfigurement, disability or death. These diseases are contracted from the bites of infected insects or animals, from contaminated water sources or foods and from poor hygiene and sanitation practices. The formation of the NTDs, as a group of infections, was a product of the Millennium Development Goals; the term coined in the early 2000s to delineate these diseases from the well-funded and well supported HIV/AIDs, malaria and tuberculosis for which there was significant advocacy. NTDs are neglected in terms of advocacy, funding (research, development and control) and global policy and media attention.
To better understand the current status of the NTDs, a number of mixed methods studies were undertaken within the body of work comprising this PhD, including: 1) an assessment of the current aetiology of NTDs, including symptoms, diagnostics, treatments and their global burden as defined by the Global Burden of Disease Study; 2) an evaluation on the effectiveness of community health education as a cost effective and long-lasting intervention geared towards behavioural changes as NTD control; 3) a review of the research and development funding of NTDs; 4) a scoping review of the impact that the global pandemic of COVID-19 has had on NTDs and lastly, 5) a case study to explore the impacts of COVID-19 on NTDs within Zambia, focussing on the opinions of local experts; policy makers, researchers, and international organizations working on NTDs in the country.
While the full implications of long-term effects of COVID-19 on the NTDs remains to be validated, the evidence presented in this thesis shows that control and treatment of NTDs was globally and universally affected by COVID-19, setting back years and in some cases, decades of progress towards control and elimination of these diseases. Interventions for disease control were delayed or cancelled and there is a resultant shortage of funds to complete NTD interventions as planned.
A significant and major hurdle to funding for NTDs is a lack of transparency in reporting of funding for NTDs from 2007 to 2023, from all agencies involved pre- and post- emergence of COVID-19. The NTDs routinely receive a fraction of the financial support required for their elimination as a public health problem and the funds vary annually making long term planning for control programs difficult. Without knowledge of the funds allocated and actual spend on NTD interventions and control programs, it is difficult to argue for increased budget allocation for the NTDs. Financing for NTDs needs to be adequate and consistent to reach and maintain the World Health Organization’s goals of eliminating NTDs by 2030.
Transparency on the side of donor governments providing foreign aid and recipient governments investing aid, to show how much funding is being provided and how those funds are allocated and utilized is essential. Increased transparency and long-term planning for NTDs would aid the global community to meet the targets in place for many of these conditions by 2030.
While advocacy is critical for resourcing for NTD research and development funding and for control activity the importance of community health education to NTDs, but specifically neglected zoonotic diseases (NZD) and their control program cannot be overstated. Giving communities educational programming adapted to their cultural practices, providing information about prevention, treatment, and hygiene can increase uptake of intervention programs and reduce the burden of NZDs and make interventions more cost effective. When introduced through schools using age-appropriate materials, there is greater potential for long term behavioural changes also reducing the burden of NZDs.
The case study in Zambia provides a unique look into the challenges of COVID-19 on the policy makers, researchers, governmental employees and international organizations working with NTDs before and after COVID-19. There are an infinite number of ways to divide funding to improve health, and there are no perfect answers on how to prioritize the elimination of NTDs
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