VictorJuiz/thesis huggingface dataset:
Developing evidence-based strategic plans for malaria control and elimination in Indonesia

Controlling and eliminating malaria in Indonesia is a challenging endeavour. Evidence-based strategic plans should be critically formulated to overcome a complex mosaic of infection risk across the 5000-km-long archipelago of thousand islands and distinctive habitats. This project aimed to thoroughly explore the challenges and opportunities for controlling/eliminating malaria and present the application of malaria cartographic tools to allow malaria control agencies and their partners to comprehensively assess the prospects for reaching pre-elimination, monitor and evaluate the effectiveness of future strategies against the baseline generated.
First, the historical context of malaria in Indonesia and important methods of control and their impact in the context of the political systems that supported them was comprehensively described. A series of distribution maps of twenty Anopheles malaria vector mosquitoes in Indonesia were also produced, supported by comprehensive reviews of each species’ bionomics and susceptibility to insecticides.
Then, the application of malaria cartographic tools for malaria control/elimination in Indonesia was explored. The first high spatial resolution (1 x 1 km) baseline endemicity maps of Plasmodium falciparum and P. vivax malaria were generated, together with corresponding estimates of population at risk and clinical burdens of each species in 2010. Low malaria prevalences of these parasites were predicted in western areas, with high prevalences in eastern Indonesia. Over 132 million people in Indonesia lived at risk of P. falciparum transmission with 70% of them in areas of unstable transmission and 30% in stable transmission. There were an estimated 7.7 million P. falciparum clinical cases across the populations at risk. Meanwhile, nearly 130 million people lived at risk of P. vivax malaria with 79% living in unstable and 21% in stable transmission areas. This infection caused 1.5 million estimated clinical cases in 2010. Both estimates were 30-fold and 6-fold higher than routinely reported numbers, respectively.
Finally, this project revealed the substantial multi-faced problems that impede current efforts towards the pre-elimination agenda. High rates of undiagnosed clinical cases, insufficient competence of malaria microscopy, inadequate primaquine dosing against P. vivax malaria infections, insufficient evidence of vector control interventions, wide diversities of vector mosquitoes and their bionomics, mosquito resistance against insecticides and inadequate malaria surveillance systems are challenging the task of controlling and eliminating malaria. A diverse range of strategies enabling locally-specific approaches must be implemented for controlling and eliminating malaria in Indonesia. Strategic recommendations are listed and future research priorities are proposed for further study.

Keywords: Elimination
Indonesia
GIS
Malaria
Advisor: Hay, S
The ecology of vascular epiphytes in the Peruvian Andes

Little is known about the composition of tropical epiphytic communities and the influence of environmental variables on community composition. In this thesis I quantify the diversity and biomass of bromeliads, and other vascular epiphytes along an altitudinal transect on the eastern slope of the southeast Peruvian Andes and then look for species’ adaptations related to patterns of diversity and biomass. I compare patterns with those of woody species. Bromeliad species, like tree species, were found to form ecological zones related to climate. The lowest altitude ecological zone (below 1250 m) is the lowland rainforest (LRF), which has the warmest climate and highest evapotranspiration. In LRF vascular epiphytes are less prominent than other ecological zones, with the lowest bromeliad species richness and lowest vascular epiphyte biomass. However, low water-availability gives rise to most variable shoot morphology of bromeliads. The tropical montane forest (TMF), between 1250 m and 2250 m, is intermediate in climate between the LRF and the tropical montane cloud forest (TCF). The TMF has the highest α-diversity, but species richness is lower than the TCF. The shoot morphology of bromeliads is intermediate between TCF and LRF. The highest altitude ecological zone with forest is the TCF (above 2250 m). The TCF has the highest bromeliad species richness, and lowest diversity of shoot forms. The low diversity of shoot forms represents the need for a large phytotelm (water-impounding shoot) to intercept and store precipitation. The TCF has the highest vascular epiphyte biomass, although the biomass is variable as a consequence of the natural disturbance caused by landslides. Along the transect bromeliad species with CAM photosynthesis are only present in the LRF. Terrestrial bromeliad distribution records covering the Neotropics show CAM photosynthesis is more prevalent in drier environments showing that CAM photosynthesis is primarily an adaptation to drought. Epiphytic bromeliads, pre-adapted to a water-stressed environment show no differences in presence along rainfall gradients, but species with CAM photosynthesis occupy warmer environments.

Keywords: Peru
Bromeliaceae
Andes
vascular epiphytes
biomass
Advisor: Brown, N
Smith, J
Malhi, Y
A microscopic theory of the alpha-nucleus optical potential

A semiclassical theory of the optical potential based on Feynman's path integral formalism is proposed.
The new approach gives an expression for the time integral of the optical potential in terms of the ground state to ground state transition amplitude. The transition amplitude is first calculated by perturbation theory. Then the formalism is applied to the study of the imaginary part of the optical potential for a-elastic scattering on 160 and 40Ca. The projectile is treated as a point-like particle and the target is described by the shell model. The relative motion is calculated in a semiclassical approximation. The intermediate states of the target are lp-lh states and the centre-of-mass spurious excitations are explicitly calculated. The absorption of flux from the elastic channel due only to collective excitations is evaluated by taking as intermediate states only the giant quadrupole and monopole states. The relation to phenomenological potentials is clarified by comparing time integrals along classical trajectories.
In order to test the validity of perturbation theory the ground state to ground state transition amplitude is also calculated by solving a set of coupled channel equations. Time integrals of the imaginary part of the optical potential are compared with the results obtained by perturbation theory. Information about the real part of the potential is also extracted. Finally a comparison is made with other theories of the optical potential which use perturbation theory. Some final remairfcs and suggestions for future developments conclude this work.

Advisor: Brink, D
A study of the jiao, a Taoist ritual, in Kam Tin, in the Hong Kong New Territories

In this fieldwork study of the 1975 Kam Tin jiao, Chapter 1 discusses the setting, showing the social system of Kam Tin, analysed in terms of genealogical and community aspects. The discussion of the genealogical aspects shows that Kam Tin does not conform to the standard model of the "lineage". The occupational structure of one of the Kam Tin villages is discussed, as well as the population of the local area. Finally, a brief introduction to the jiao, in Kam Tin a decennial ritual, is provided, showing the genealogical and community based aspects of its organisation and performance.
Chapter 2 treats the history and mythology of the Kam Tin jiao, explaining the circumstances of the early Qing history which led to its foundation.
Chapter 3 examines the organisation of the jiao in terms of committee membership, funding, and the ritual timetable.
Chapter 4 discusses the background and organisation of the ritual practitioners. These are the Ritual Leaders (chosen through a block throwing competition in the temple associated with the jiao) and the Taoist priests.
Chapter 5 discusses the preparatory rituals of the jiao, including the two rites of Memorial presentation. The relationship between the preparatory rituals and the main rites of the jiao is delineated.
Chapter 6 discusses the arrangement of the ritual area before the jiao's major rites.
Chapter 7 continues with a chronological description and analysis of the main rites of the jiao.
Chapter 8 discusses the jiao rites taking place after the period of abstention from certain kinds of foods and sexual relations. This chapter discusses the rationale for the collection and return of divinities from specific sites during the course of the jiao.
Chapter 9 concludes the discussion by analysing the Kam Tin jiao both comparatively and on its own terms.
The jiao is shown to be a worship of deities and an act of salvation and/or placation for hungry ghosts, aimed at securing well-being and fortune for the community. On another level of analysis, however, the rites in Kam Tin are a re-ordering of an imperfect society.
Essays on the financial governance of firms

Four essays, or chapters, model the capital structure, governance, and investment decisions as part of a sequential game. Each chapter is separate in its context, assumptions, and conclusions. The titles of the chapters are below. Abstracts of each essay or chapter can be found at the beginning of each chapter. The titles of the chapters or essays are as follows: I. Managerial Ownership with Rent-Seeking Employees, II. Financing Professional Partnerships, III. Sunk Cost Efficiency with Identical Competitors, and IV. Business Stealing and Bankruptcy. With the exception of Chapter III, which is meant to complement Chapter IV, these essays argue that the structure of financial contracts can affect the real behavior of firms. The first chapter argues that financial governance policies affect the behavior of rank-and-file employees. In Chapter II, the governance and capital structure of professional service firms affects clients’ expectations of the firm’s quality. In Chapter IV, the enforcement of financial contracts by bankruptcy courts affects the number of firms that enter and exit the industry.

Keywords: firm entry
unions
CEO pay
firm exit
bankrupcy
professional partnerships
debt
capital structure
Advisor: Roberts, K
Investigating the role of the fat mass and obesity associated gene (Fto) in obesity

In 2007, a genome wide association study identified a SNP in intron 1 of FTO with increased BMI. Homozygous risk allele carriers are on average three kg heavier than those homozygous for the protective allele. Mouse models have been made, including a conditional knockout, which is lean when globally expressed, as well as a conditional overexpression allele, which has increased body weight when globally expressed. The results from these and other studies suggest that the FTO SNPs lead to weight gain by increasing FTO activity and/or expression.
Adult inactivation of Fto using the tamoxifen inducible Cre demonstrated that removal of Fto may be as deleterious as overexpression, with the adult knockout mice having increased fat mass and decreased lean mass. It also supported the role FTO plays in development as adult inactivation of Fto did not increase mortality rates as seen in the global Fto-/- pups. This study also revealed the importance of effective energy expenditure analysis in the mouse.
I have confirmed a link between Fto-/- and increased mortality, which may be caused by alterations to developmental processes. Fto-/- reduces cilia formation in MEFs and results in dysregulated cilia formation in specific tissues in Fto-/- embryos. Levels of FTO also appear to affect adipogenic differentiation, which could be due to altered WNT/β-CATENIN signalling.
Pharmacological inhibition of FTO was a success in vitro and a compound screen identified FG2216, which could be used in vivo to inhibit FTO. The in vivo effects of FG2216 at 60 mg/kg/2days did not affect body weight or composition in the mouse.
My research suggests that there is dysregulation of gut hormones and neuronal signalling pathways in the FTO overexpression mice, which could cause the hyperphagia and increased body weight. These studies add to our current knowledge of FTO function, and suggest a role for FTO in control of body composition, development, and satiety signalling.

Keywords: fat mass and obesity gene
Obesity
Metabolism
GWAS
FTO
Genetics
Genome Wide Association
Advisor: Cox, R
Mellor, J
Hemisphere asymmetries in schizophrenia

Previous research into everyday conception of personal relationships has been sparse and fragmented, and the various specialisms fail to deal with the broader issue of interpersonal understanding. Following review of the research and theoretical background, with particular reference to changing paradigms, a holistic approach is proposed for an exploration linking the content of explanation and reflection about relationships with the incidence of conceptualising. The methodology, employing content analysis, illustrative studies and a musical analogue, is outlined.
Initially focusing on verbalised conception in the form of accounts, a procedure of 'simulated correspondence with a confidant' was employed to facilitate unrestricted disclosures in general descriptions of relationships. Three coding schemes were devised for content analysis of accounts (and for independent use in subsequent research). These pertained to: (1) specific concepts and themes; (2) explanation of interpersonal effect and significance; and (3) inter-subjectivity in accounts. Overall indications from the content analyses are that accounts are characterised by superficiality of detail and insight, and concentrate more on basic viability, and on social and visible aspects of personal relationships than on intimate and psychological aspects. The limitations of content analysis, and the deficiencies disclosed, suggest attention should be given to omission in content as much as inclusion, and also to the prior issues of motivation and the extent of relationship 'mindfulness'. A musical analogy (with particular reference to representation, knowledge and appreciation) is employed to advance the exploration beyond the linguistic aspects of conception to a more general model of relationship awareness.
A second set of studies turn to (1) the frequency and occasioning of reflection on relationships; (2) reappraisal over time; (3) interest in relationships compared with other subjects of general interest; and (4) factors which disincline conscious relationship deliberation and analysis. There are indications throughout of a sex difference, with men as less reflective, less inclined to participate in providing accounts, and less interested in personal relationships. Disincentives are suggested, and a theory of 'relationship mindlessness' is discussed, connecting impoverishment of content and incidence with the late emergence of 'personal relationships' as a subject of formal scholarly enquiry in psychology.
It is proposed that such mindlessness, and associated disincentives, are implicated in relationship problems, and that extension of relationship education, knowledge and interest are indicated. The practicalities and possible form of learning about relationships and consciousness-raising were explored in a trial relationship understanding course. Counter-indications for such consciousness-raising were evaluated by analogy with music appreciation.

Advisor: Claridge, G
A comparative study of volunteering and giving

The main research question in this thesis explores why some people volunteer and give money compared to those that do not. The thesis builds on existing research that explains volunteering and giving, but is primarily concerned with showing how the social environment – or the context – in which people live can explain individual decisions to volunteer and give. This thesis answers three main research questions with this central theme in mind. First, how do the background characteristics of people explain whether they volunteer or give? Second, net of background characteristics of people, how does the social environment (context) that people live in explain volunteering and giving? Third, how do background characteristics of people and the social environment in which they live interact to explain volunteering and giving? Each of the four empirical chapters focuses on research questions that have received limited attention in the literature, while also utilizing relatively unique data, in relatively unique contexts.
The main results of this study are as follows. Comparatively, the shared profile of a volunteer and charitable giver is someone who is middle aged, more educated, married, richer, healthier, and a religious service attendee. Contextual country characteristics also displayed an independent effect of these individual-level characteristics: religious diversity and belonging to a religious minority group was associated with a greater likelihood of volunteering, but are not associated with giving. Income inequality is associated with a decreased likelihood of volunteering and giving for respondents in developed countries, whereas the opposite is true for respondents in developing countries, supporting Wilkinson’s relative income hypothesis. A curvilinear relationship exists between national devoutness and volunteering, whereas a strong positive correlation exists between national devoutness and giving. Females are more likely to volunteer and give in societies that exhibit more gender equality; and the lower educated are more likely to volunteer in more educated societies, but that they are not more likely to give in these societies. There is no support for the idea that income disparities in volunteering and giving are exacerbated in more socially unequal societies.
In England, there was no support for the idea that a stable residential area promotes volunteering and giving among adults, while neighbourhood deprivation and ethnic diversity were strong negative predictors of both behaviours. Among the youth demographic in England, religious diversity of schools is not associated with any form of civic engagement. Ethnic diversity is positively related to school extra curricular activities, but negatively with youth club participation. Youths attending private schools were more likely to take part in school-based extra-curriculars, but less likely to take part in out of school clubs and groups.

Keywords: pro-social behaviour
social context
quantitative methods
charitable giving
multilevel modelling
social capital
social cohesion
volunteering
Advisor: De Graaf, ND
Pathogenic mycobacteria achieve cellular persistence via lipid-mediated inhibition of the Niemann-Pick disease type C pathway

M.tuberculosis, the causative agent of human tuberculosis, is able to achieve long-term persistence within host organism macrophages. This persistence is achieved via the ability of the mycobacterium to prevent phagosomal-lysosomal fusion. The mechanisms by which fusion is inhibited remain incompletely understood. Here we provide evidence supporting a mechanistic link between infection with pathogenic mycobacteria and the cellular pathway defective in the rare lysosomal storage disorder Niemann-Pick disease type C (NPC). We observed that NPC phenotypes, including lipid storage and reduced lysosomal calcium release, can be induced in wild-type murine and human macrophages by infection with pathogenic mycobacteria. This phenotype induction did not occur following infection with the non-pathogenic M.smegmatis. Phenotype induction could be achieved in the absence of the mycobacteria using lipids from the mycobacterial cell walls. The importance of mycobacterial cell wall lipids to mycobacterial virulence has been well-documented. This lipid-mediated inhibition likely occurs through the NPC1 protein. Susceptibility to phenotype induction was inversely proportional to levels of functional NPC1, whilst a pre-existing dysfunction in the NPC pathway (either stemming from mutation or pharmacological inhibition) rendered cells less able to clear non-pathogenic mycobacteria. Finally, we demonstrate that therapies for NPC, particularly curcumin, are able to promote clearance of mycobacteria from infected macrophages. NPC therapies may hold promise for a new approach to the treatment of tuberculosis.

Keywords: NIEMANN-PICK DISEASE TYPE C
LYSOSOME
PHARMACOLOGY
TUBERCULOSIS
LYSOSOMAL STORAGE DISORDERS
Advisor: Platt, F
The functional consequences of autoimmune variants in the tyrosine kinase 2 gene region

The tyrosine kinase 2 (TYK2) gene was first implicated in autoimmune disease in 2009 when a nonsynonymous single nucleotide polymorphism (nsSNP) in TYK2 was reported to be associated with multiple sclerosis (MS). The immunological function of TYK2, as a kinase involved in signal transduction downstream of numerous different cytokine receptors, further strengthened the candidacy of the gene as an MS-relevant risk factor. More recently, this nsSNP has been associated with several other autoimmune conditions. In addition, another three different SNPs in the region have been found to be associated with a number of autoimmune diseases, sometimes in opposing directions. Considering the complex genetic association pattern that is emerging for the TYK2 region across autoimmune conditions, it was hypothesised that this complexity reflects shared but also distinct pathogenic mechanisms, with the consequences of disease-associated SNPs being unlikely to all be restricted to genotype-dependent effects influencing TYK2. Therefore, the main aim of the work presented in this thesis has been to address this hypothesis by investigating the functional consequences of the disease-associated SNPs in the TYK2 gene region.
Using an in vitro cell line system and primary human immune cells, obtained from a genotype-selectable donor cohort, protection at the MS-associated nsSNP was found to correlate with reduced TYK2-mediated signalling downstream of the type I interferon receptor. However, other cytokine signalling pathways were not affected, indicating a greater specificity to the function of TYK2 than has previously been appreciated. For the other SNPs in the region, substantial effects on TYK2 were not observed but immune cell subset-specific correlations with RNA-level expression of other genes in the region were identified. Thus, this is the first study to support the concept that a careful cross-comparative analysis of SNP association patterns in a single genomic region across multiple autoimmune diseases can have significant implications for enabling the delineation of pathways common or specific to different conditions, and this is of particular importance for drug repositioning strategies.

Keywords: genetics
Autoimmunity
Advisor: Fugger, L