Data feedback and behavioural change intervention to improve primary care prescribing safety (EFIPPS) : multicentre, three arm, cluster-randomised controlled trial

Funding and trial registration: Scottish Government Chief Scientist Office grant CZH/3/17. ClinicalTrials.gov registration NCT01602705.

A Study of the Behavioural and Affective Profile of Inpatient Adolescent Girls Presenting a Restrictive Anorexia Nervosa

Essai doctoral d'intégration présenté à la Faculté des Études Supérieures et Postdoctorales en vue de l'obtention du grade de Docteur en psychologie (D.Psy.), en psychologie clinique

Adapting Arthur: The transformations and adaptations of Wirnt von Graffenberg's Wigalois

The stories of King Arthur and his noble knights have fascinated audiences for many centuries and continue to being retold and fashioned to attract modern audiences. Amongst these stories is the tale of Wigalois, the son of the reputable Gawain. This dissertation traces the story of Wigalois across different languages, cultures, and media in order to show how this is a shared German-Yiddish narrative. Furthermore, this dissertations challenges traditional understanding of adaptation within a diachronic and teleological framework by uncovering dialogical and dynamic processes inherent in this narrative tradition. Using the theoretical framework of a combined Adaptation Studies and Medieval Literature Studies’ notions of unstable texts my argumentation focuses on eight specific examples: Wirnt von Grafenberg’s Wigalois (1st half 13th ct.), Italian murals from the fourteenth century, Wigoleis von dem Rade (1483/93), Viduvilt (Yiddish, 16th ct.), Johann Christoph Wagenseil’s Belehrung der Jüdisch-Teutschen Red- und Schreibart (Yiddish and German, 1715), Gabein (Yiddish, 1789), the illustrations by Ludwig Richter (before 1851), and Die phantastischen Abenteuer der Glücksritters Wigalois (Comic, German, 2011).

Pathogen-Specific Adaptations to Conserved Signaling Pathways in Cryptococcus neoformans

Cryptococcus neoformans is an opportunistic fungal pathogen that causes significant disease worldwide. Even though this fungus has not evolved specifically to cause human disease, it has a remarkable ability to adapt to many different environments within its infected host. C. neoformans adapts by utilizing conserved eukaryotic and fungal-specific signaling pathways to sense and respond to stresses within the host. Upon infection, two of the most significant environmental changes this organism experiences are elevated temperature and high pH.

Conserved Rho and Ras family GTPases are central regulators of thermotolerance in C. neoformans. Many GTPases require prenylation to associate with cellular membranes and function properly. Using molecular genetic techniques, microscopy, and infection models, I demonstrated that the prenyltransferase, geranylgeranyl transferase I (GGTase I) is required for thermotolerance and pathogenesis. Using fluorescence microscopy, I found that only a subset of conserved GGTase I substrates requires this enzyme for membrane localization. Therefore, the C. neoformans GGTase I may recognize its substrate in a slightly different manner than other eukaryotic organisms.

The alkaline response transcription factor, Rim101, is a central regulator of stress-response genes important for adapting to the host environment. In particular, Rim101 regulates cell surface alterations involved in immune avoidance. In other fungi, Rim101 is activated by alkaline pH through a conserved signaling pathway, but this pathway had yet been characterized in C. neoformans. Using molecular genetic techniques, I identified and analyzed the conserved members of the Rim pathway. I found that it was only partially conserved in C. neoformans, missing the components that sense pH and initiate pathway activation. Using a genetic screen, I identified a novel Rim pathway component named Rra1. Structural prediction and genetic epistasis experiments suggest that Rra1 may serve as the Rim pathway pH sensor in C. neoformans and other related basidiomycete fungi.

To explore the relevance of Rim pathway signaling in the interaction of C neoformans with its host, I characterized the Rim101-regulated cell wall changes that prevent immune detection. Using HPLC, enzymatic degradation, and cell wall stains, I found that the rim101Δ mutation resulted in increased cell wall chitin exposure. In vitro co-culture assays demonstrated that increased chitin exposure is associated with enhanced activation of macrophages and dendritic cells. To further test this association, I demonstrated that other mutant strains with increased chitin exposure induce macrophage and dendritic cell responses similar to rim101Δ. We used primary macrophages from mutant mouse lines to demonstrate that members of both the Toll-like receptor and C-type lectin receptor families are involved in detecting strains with increased chitin exposure. Finally, in vivo immunological experiments demonstrated that the rim101Δ strain induced a global inflammatory immune response in infected mouse lungs, expanding upon our previous in vivo rim101Δ studies. These results demonstrate that cell wall organization largely determines how fungal cells are detected by the immune system.

Behavioural Genetics in the Postgenomics Era

There is growing evidence that the complexity of higher organisms does not correlate with the ‘complexity’ of the genome (the human genome contains fewer protein coding genes than corn, and many genes are preserved across species). Rather, complexity is associated with the complexity of the pathways and processes whereby the cell utilises the deoxyribonucleic acid molecule, and much else, in the process of phenotype formation. These pro- cesses include the activity of the epigenome, noncoding ribonucleic acids, alternative splicing and post-transla- tional modifications. Not accidentally, all of these pro- cesses appear to be of particular importance for the human brain, the most complex organ in nature. Because these processes can be highly environmentally reactive, they are a key to understanding behavioural plasticity and highlight the importance of the developmental process in explaining behavioural outcomes.

A Study of the Behavioural and Affective Profile of Inpatient Adolescent Girls Presenting a Restrictive Anorexia Nervosa

Essai doctoral d'intégration présenté à la Faculté des Études Supérieures et Postdoctorales en vue de l'obtention du grade de Docteur en psychologie (D.Psy.), en psychologie clinique

Intraspecific Behavioural Diversity in a Freshwater Zooplankton: A study of the fitness consequences of vertical migration behaviour for distinct morphs of Daphnia pulicaria

The literature on niche separation and coexistence between species is large, but there is widespread variation in behavioural strategy between individuals of the same species that has received much less attention. Understanding what maintains this diversity is important because intraspecific behavioural diversity can affect population dynamics and community interactions. Multiple behavioural strategies can arise either as phenotype-dependent ‘conditional strategies’, where phenotypic variation causes individuals to adopt different strategies for optimizing fitness, or as internally-independent ‘alternative strategies’, where multiple fitness peaks exist for individuals and strategic ‘choice’ remains plastic. Though intraspecific variation in stable phenotypes is known to maintain intraspecific behavioural diversity through conditional strategies, when internal conditions are highly plastic or reversible, it is not clear whether individual behaviours are maintained as conditional strategies, or as alternative strategies of equal fitness. In this study, I combine an observational and experimental approach to identify the likely mechanisms maintaining behavioural diversity between hemoglobin-rich and hemoglobin-poor morphs in a natural population of Daphnia pulicaria. In Round Lake, individuals with low hemoglobin migrate daily from the hypolimnion to the epilimnion, whereas individuals with high hemoglobin remain in the hypolimnion. Using high-resolution depth and time sampling, I discovered behavioural diversity both within and among hemoglobin phenotypes. I tested the role of hemoglobin phenotype in maintaining behavioural diversity using automated migration robots that move individuals across the natural environmental gradients in the lake. By measuring the fitness of each morph undergoing either a natural migration behaviour, or the migration of the opposite morph, I found that the fitness of hemoglobin rich and poor morphs in their natural behaviour does not differ, but that Hb-rich individuals can obtain equal fitness from either behaviour, while Hb-poor morphs suffer substantial drops in survivorship in the alternate migration behaviour. Thus, migration behaviour in this system exists as a conditional strategy for some individuals, and as alternative strategies of equal fitness for others. The results of this study suggest that individual limits in the expression of highly flexible internal conditions can reinforce intraspecific behavioural diversity. Few studies have measured the fitness consequences of switching migration strategies and this study provides a rare example in the field.

Walking with God through Nature: An Examination of John Flavel’s Behavioural Instructions on Matters Related to Christian Piety

John Flavel was a Reformed Puritan of the seventeenth-century who wrote a series of devotional guides that offered instructions drawn from Christian mystical traditions on how to improve religious activities as a means of ecstatically encountering God. Evaluating the efficacy of these instructions from a scientifically-based behavioural perspective, this study has found that Flavel’s techniques were likely helpful to his readers in facilitating socially normative ecstatic experiences through ordinary Christian practice. Furthermore, discovering that Flavel promoted the use of these techniques for engaging with ecological materials in the wilderness and country-side, this essay proposes that Flavel introduced his readers to effectual manners that could help them ecstatically encounter God during the practice of meditational nature-based walks.

Digital anthropology and educational eGames: learning through behavioural patterns in digital, game-based contexts

The selected publications are focused on the relations between users, eGames and the educational context, and how they interact together, so that both learning and user performance are improved through feedback provision. A key part of this analysis is the identification of behavioural, anthropological patterns, so that users can be clustered based on their actions, and the steps taken in the system (e.g. social network, online community, or virtual campus). In doing so, we can analyse large data sets of information made by a broad user sample,which will provide more accurate statistical reports and readings. Furthermore, this research is focused on how users can be clustered based on individual and group behaviour, so that a personalized support through feedback is provided, and the personal learning process is improved as well as the group interaction. We take inputs from every person and from the group they belong to, cluster the contributions, find behavioural patterns and provide personalized feedback to the individual and the group, based on personal and group findings. And we do all this in the context of educational games integrated in learning communities and learning management systems. To carry out this research we design a set of research questions along the 10-year published work presented in this thesis. We ask if the users can be clustered together based on the inputs provided by them and their groups; if and how these data are useful to improve the learner performance and the group interaction; if and how feedback becomes a useful tool for such pedagogical goal; if and how eGames become a powerful context to deploy the pedagogical methodology and the various research methods and activities that make use of that feedback to encourage learning and interaction; if and how a game design and a learning design must be defined and implemented to achieve these objectives, and to facilitate the productive authoring and integration of eGames in pedagogical contexts and frameworks. We conclude that educational games are a resourceful tool to provide a user experience towards a better personalized learning performance and an enhance group interaction along the way. To do so, eGames, while integrated in an educational context, must follow a specific set of user and technical requirements, so that the playful context supports the pedagogical model underneath. We also conclude that, while playing, users can be clustered based on their personal behaviour and interaction with others, thanks to the pattern identification. Based on this information, a set of recommendations are provided Digital Anthropology and educational eGames 6 /216 to the user and the group in the form of personalized feedback, timely managed for an optimum impact on learning performance and group interaction level. In this research, Digital Anthropology is introduced as a concept at a late stage to provide a backbone across various academic fields including: Social Science, Cognitive Science, Behavioural Science, Educational games and, of course, Technology-enhance learning. Although just recently described as an evolution of traditional anthropology, this approach to digital behaviour and social structure facilitates the understanding amongst fields and a comprehensive view towards a combined approach. This research takes forward the already existing work and published research onusers and eGames for learning, and turns the focus onto the next step — the clustering of users based on their behaviour and offering proper, personalized feedback to the user based on that clustering, rather than just on isolated inputs from every user. Indeed, this pattern recognition in the described context of eGames in educational contexts, and towards the presented aim of personalized counselling to the user and the group through feedback, is something that has not been accomplished before.

Scale-dependent to scale-free: daily behavioural switching and optimized searching in a marine predator

Highlights • We study diel behavioural differences in activity patterns in bigeye tuna. • Daytime activity patterns showed scale free movements consistent with searching. • Night-time activity showed simpler movements indicative of rich patch exploitation. • The results confirm predictions of the Lévy foraging hypothesis.

Scale-dependent to scale-free: daily behavioural switching and optimized searching in a marine predator

Highlights • We study diel behavioural differences in activity patterns in bigeye tuna. • Daytime activity patterns showed scale free movements consistent with searching. • Night-time activity showed simpler movements indicative of rich patch exploitation. • The results confirm predictions of the Lévy foraging hypothesis.

Optimal Scaffolding Methods for Students with Emotional and Behavioural Disorders

Optimal assistance of an adult, adapted to the current level of understanding of the student (scaffolding), can help students with emotional and behavioural problems (EBD) to demonstrate a similar level of understanding on scientific tasks, compared to students from regular education (Van Der Steen, Steenbeek, Wielinski & Van Geert, 2012). In the present study the optimal scaffolding techniques for EBD students were investigated, as well as how these differ from scaffolding techniques used for regular students. A researcher visited five EBD students and five regular students (aged three to six years old) three times in a 1,5 years period. Student and researcher worked together on scientific tasks about gravity and air pressure, while the researcher asked questions. An adaptive protocol was used, so that all children were asked the same basic questions about the mechanisms of the task. Beside this, the researcher was also allowed to ask follow-up questions and use scaffolding methods when these seemed necessary. We found a bigger amount of scaffolding in the group of EBD students compared to the regular students. The scaffolding techniques that were used also differed between the two groups. For EBD students, we saw more scaffolding strategies focused on keeping the student committed to the task, and less strategies aimed at the relationship between the child and the researcher. Furthermore, in the group of regular students we saw a decreasing trend in the amount of scaffolding over the course of three visits. This trend was not visible for the EBD students. These results highlight the importance for using different scaffolding strategies when working with EBD students compared to regular students. Future research can give a clearer image of the differences in scaffolding needs between these two groups.

A Cognitive Behavioural Therapy approach to Suicide Assessment and Intervention

An evaluation of training delivered to undergraduate nursing students on the therapeutic benefits and efficacy of the application of a basic CBT model and the use of simple CBT techniques for the assessment and intervention of service users with suicidal intent.

Characteristics of change triggered temper outbursts in children with PWS and ASD and how these may impact on the efficacy of behavioural intervention strategies.

Background
Temper outbursts are prevalent in individuals with PWS and are often triggered by unexpected changes to routines or plans. However, such outbursts are also common in individuals with several other neurodevelopmental disorders, including those with a diagnosis of autism spectrum disorder (ASD). We compared the profile of temper outbursts in children with PWS to that in children with ASD. We examined whether differences in the temper outburst profile predicted differences in the outcomes of two caregiver led intervention strategies aiming to reduce change triggered outbursts.
Methods and results
Thirteen 7-15 year olds with PWS – taking part in a larger study involving 60 children evidencing temper outbursts following changes – were individually matched for age to children with ASD (mean ages: 10.70; 10.76 yrs). Caregivers participated in a structured/semi-structured interview on children's outbursts; completed a web-based outburst diary over a 6 month baseline; and are currently using either a change signalling intervention to reliably warn children of forthcoming changes; or a planning ahead intervention to reduce children's exposure to unexpected changes.
As reported at interview, on average, children with PWS showed more frequent temper outbursts than those with ASD (closer to daily vs. weekly). For seven children with PWS and six with ASD, 60% or more of their temper outbursts were reported to be triggered by changes. Whilst outbursts had similar durations when triggered by changes or by other events in children with PWS; change triggered outbursts in children with ASD were generally shorter. The most commonly reported outburst components in children with PWS included indicators of heightened emotional arousal but this was not the case for children with ASD. Data on behavioural change associated with each of the intervention strategies will be discussed.
Conclusions
Change triggered temper outbursts can be a problem for children PWS and ASD, however subtle differences appear to exist in the profile of these outbursts. Some of these differences may be relevant for the expected efficacy of different behavioural intervention strategies that target outbursts.
Summary
Temper outbursts (tantrums) were compared in children with PWS or autism spectrum disorder before and during use of one of two helping strategies. Helping strategies were led by caregivers and aimed to reduce outbursts that follow changes to routines or plans by making such changes more predictable, or by reducing the quantity of changes. Characteristics of outbursts may be important to help us predict which helping strategies may be most effective.