Development of Imaging Mass Spectrometry Analysis of Lipids in Biological and Clinically Relevant Applications

La spectrométrie de masse mesure la masse des ions selon leur rapport masse sur charge. Cette technique est employée dans plusieurs domaines et peut analyser des mélanges complexes. L’imagerie par spectrométrie de masse (Imaging Mass Spectrometry en anglais, IMS), une branche de la spectrométrie de masse, permet l’analyse des ions sur une surface, tout en conservant l’organisation spatiale des ions détectés. Jusqu’à présent, les échantillons les plus étudiés en IMS sont des sections tissulaires végétales ou animales. Parmi les molécules couramment analysées par l’IMS, les lipides ont suscité beaucoup d'intérêt. Les lipides sont impliqués dans les maladies et le fonctionnement normal des cellules; ils forment la membrane cellulaire et ont plusieurs rôles, comme celui de réguler des événements cellulaires. Considérant l’implication des lipides dans la biologie et la capacité du MALDI IMS à les analyser, nous avons développé des stratégies analytiques pour la manipulation des échantillons et l’analyse de larges ensembles de données lipidiques. La dégradation des lipides est très importante dans l’industrie alimentaire. De la même façon, les lipides des sections tissulaires risquent de se dégrader. Leurs produits de dégradation peuvent donc introduire des artefacts dans l’analyse IMS ainsi que la perte d’espèces lipidiques pouvant nuire à la précision des mesures d’abondance. Puisque les lipides oxydés sont aussi des médiateurs importants dans le développement de plusieurs maladies, leur réelle préservation devient donc critique. Dans les études multi-institutionnelles où les échantillons sont souvent transportés d’un emplacement à l’autre, des protocoles adaptés et validés, et des mesures de dégradation sont nécessaires. Nos principaux résultats sont les suivants : un accroissement en fonction du temps des phospholipides oxydés et des lysophospholipides dans des conditions ambiantes, une diminution de la présence des lipides ayant des acides gras insaturés et un effet inhibitoire sur ses phénomènes de la conservation des sections au froid sous N2. A température et atmosphère ambiantes, les phospholipides sont oxydés sur une échelle de temps typique d’une préparation IMS normale (~30 minutes). Les phospholipides sont aussi décomposés en lysophospholipides sur une échelle de temps de plusieurs jours. La validation d’une méthode de manipulation d’échantillon est d’autant plus importante lorsqu’il s’agit d’analyser un plus grand nombre d’échantillons. L’athérosclérose est une maladie cardiovasculaire induite par l’accumulation de matériel cellulaire sur la paroi artérielle. Puisque l’athérosclérose est un phénomène en trois dimension (3D), l'IMS 3D en série devient donc utile, d'une part, car elle a la capacité à localiser les molécules sur la longueur totale d’une plaque athéromateuse et, d'autre part, car elle peut identifier des mécanismes moléculaires du développement ou de la rupture des plaques. l'IMS 3D en série fait face à certains défis spécifiques, dont beaucoup se rapportent simplement à la reconstruction en 3D et à l’interprétation de la reconstruction moléculaire en temps réel. En tenant compte de ces objectifs et en utilisant l’IMS des lipides pour l’étude des plaques d’athérosclérose d’une carotide humaine et d’un modèle murin d’athérosclérose, nous avons élaboré des méthodes «open-source» pour la reconstruction des données de l’IMS en 3D. Notre méthodologie fournit un moyen d’obtenir des visualisations de haute qualité et démontre une stratégie pour l’interprétation rapide des données de l’IMS 3D par la segmentation multivariée. L’analyse d’aortes d’un modèle murin a été le point de départ pour le développement des méthodes car ce sont des échantillons mieux contrôlés. En corrélant les données acquises en mode d’ionisation positive et négative, l’IMS en 3D a permis de démontrer une accumulation des phospholipides dans les sinus aortiques. De plus, l’IMS par AgLDI a mis en évidence une localisation différentielle des acides gras libres, du cholestérol, des esters du cholestérol et des triglycérides. La segmentation multivariée des signaux lipidiques suite à l’analyse par IMS d’une carotide humaine démontre une histologie moléculaire corrélée avec le degré de sténose de l’artère. Ces recherches aident à mieux comprendre la complexité biologique de l’athérosclérose et peuvent possiblement prédire le développement de certains cas cliniques. La métastase au foie du cancer colorectal (Colorectal cancer liver metastasis en anglais, CRCLM) est la maladie métastatique du cancer colorectal primaire, un des cancers le plus fréquent au monde. L’évaluation et le pronostic des tumeurs CRCLM sont effectués avec l’histopathologie avec une marge d’erreur. Nous avons utilisé l’IMS des lipides pour identifier les compartiments histologiques du CRCLM et extraire leurs signatures lipidiques. En exploitant ces signatures moléculaires, nous avons pu déterminer un score histopathologique quantitatif et objectif et qui corrèle avec le pronostic. De plus, par la dissection des signatures lipidiques, nous avons identifié des espèces lipidiques individuelles qui sont discriminants des différentes histologies du CRCLM et qui peuvent potentiellement être utilisées comme des biomarqueurs pour la détermination de la réponse à la thérapie. Plus spécifiquement, nous avons trouvé une série de plasmalogènes et sphingolipides qui permettent de distinguer deux différents types de nécrose (infarct-like necrosis et usual necrosis en anglais, ILN et UN, respectivement). L’ILN est associé avec la réponse aux traitements chimiothérapiques, alors que l’UN est associé au fonctionnement normal de la tumeur.

Is Trading Behavior Stable Across Contexts? Evidence from Style and Multi-Style Investors

In this paper we study priming of identity within the context of inherent vs. contextual financial decision making. We use a sample of individual trading accounts in equity-style funds taken from one fund family to test the hypothesis that trading styles are inherent vs. contextual. Our sample contains investors who invest either in a growth fund, a value fund, or both. We document behavioral differences between growth fund investors and value fund investors. We find that their trades depend on past returns in different ways: growth fund investors tend towards momentum trading and value fund investors tend towards contrarian trading. These differences may be due to inherent clientele characteristics, including beliefs about market prices, specific personality traits and cognitive strategies that cause them to self-select into one or the other style. We use a sample of investors that trade in both types of funds to test this proposition. Consistent with the contextual hypothesis, we find that investors who hold both types of funds trade growth fund shares differently than value fund shares.

Restoring function after neuromuscular trauma: novel paradigms for enhancing volitional control of neural activity in untethered environments and vHAB, a gamified therapy platform

Thesis (Ph.D.)--University of Washington, 2016-08

Mapping Learning and Game Mechanics for Serious Games Analysis in Engineering Education

In a world where students are increasing digitally tethered to powerful, ‘always on’ mobile devices, new models of engagement and approaches to teaching and learning are required from educators. Serious Games (SG) have proved to have instructional potential but there is still a lack of methodologies and tools not only for their design but also to support game analysis and assessment. This paper explores the use of SG to increase student engagement and retention. The development phase of the Circuit Warz game is presented to demonstrate how electronic engineering education can be radically reimagined to create immersive, highly engaging learning experiences that are problem-centered and pedagogically sound. The Learning Mechanics–Game Mechanics (LM-GM) framework for SG game analysis is introduced and its practical use in an educational game design scenario is shown as a case study.

Competency Based Assessment Using Virtual Reality (VERT): Is It a Realistic Possibility ?

The education of the radiography profession is based within higher education establishments, yet a critical part of all radiography programmes is the clinical component where students learn the practical skills of the profession. Assessments therefore not only have to assess a student’s knowledge, but also their clinical competence and core skills in line with both Health and Care Professions Council and the Society and College of Radiographers requirements. This timely thesis examines the possibility of using the Virtual Environment for RadioTherapy (VERT) as an assessment tool to evaluate a student’s competence so giving the advantage of a standard assessment and relieving time pressures in the clinical department. A mixed methods approach was taken which can be described as a Quantitative Qualitative design with the emphasis being on the Quantitative element; a so called QUAN  qual design. The quantitative evaluation compared two simulations, one in the virtual reality environment and another in the department using a real treatment machine. Students were asked to perform two electron setups in each simulation; the order being randomly decided and so the study would be described as a randomised cross-over design. Following this, qualitative data was collected in student focus groups to explore student perspectives in more depth. Findings indicated that the performance between the two simulators was significantly different, p < 0∙001; the virtual simulation scoring significantly lower than the hospital based simulation overall and in virtually all parameters being assessed. Thematic analysis of the qualitative data supported this finding and identified 4 main themes; equipment use, a lack of reality, learning opportunities and assessment of competence. One other sub-theme identified for reality was that of the environment and senses.

Resilience and development: mobilizing for transformation

In 2014, the Third International Conference on the resilience of social-ecological systems chose the theme “resilience and development: mobilizing for transformation.” The conference aimed specifically at fostering an encounter between the experiences and thinking focused on the issue of resilience through a social and ecological system perspective, and the experiences focused on the issue of resilience through a development perspective. In this perspectives piece, we reflect on the outcomes of the meeting and document the differences and similarities between the two perspectives as discussed during the conference, and identify bridging questions designed to guide future interactions. After the conference, we read the documents (abstracts, PowerPoints) that were prepared and left in the conference database by the participants (about 600 contributions), and searched the web for associated items, such as videos, blogs, and tweets from the conference participants. All of these documents were assessed through one lens: what do they say about resilience and development? Once the perspectives were established, we examined different themes that were significantly addressed during the conference. Our analysis paves the way for new collective developments on a set of issues: (1) Who declares/assign/cares for the resilience of what, of whom? (2) What are the models of transformations and how do they combine the respective role of agency and structure? (3) What are the combinations of measurement and assessment processes? (4) At what scale should resilience be studied? Social transformations and scientific approaches are coconstructed. For the last decades, development has been conceived as a modernization process supported by scientific rationality and technical expertise. The definition of a new perspective on development goes with a negotiation on a new scientific approach. Resilience is presently at the center of this negotiation on a new science for development.

Mothers’ perception of recovery and satisfaction with patent medicine dealers’ treatment of childhood febrile conditions in rural communities

Background Infant mortality in rural areas of Nigeria can be minimized if childhood febrile conditions are treated by trained health personnel, deployed to primary healthcare centres (PHCs) rather than the observed preference of mothers for patent medicine dealers (PMDs). However, health service utilization/patronage is driven by consumer satisfaction and perception of services/product value. The objective of this study was to determine ‘mothers’ perception of recovery’ and ‘mothers’ satisfaction’ after PMD treatment of childhood febrile conditions, as likely drivers of mothers’ health-seeking behaviour, which must be targeted to reverse the trend. Methods Ugwuogo-Nike, in Enugu, Nigeria, has many PMDs/PHCs, and was selected based on high prevalence of childhood febrile conditions. In total, 385 consenting mothers (aged 15–45 years) were consecutively recruited at PMD shops, after purchasing drugs for childhood febrile conditions, in a cross-sectional observational study using a pre-tested instrument; 33 of them (aged 21–47 years) participated in focus group discussions (FGDs). Qualitative data were thematically analysed while a quantitative study was analysed with Z score and Chi square statistics, at p < 0.05. Results Most participants in FGDs perceived that their child had delayed recovery, but were satisfied with PMDs’ treatment of childhood febrile conditions, for reasons that included politeness, caring attitude, drug availability, easy accessibility, flexibility in pricing, shorter waiting time, their God-fearing nature, and disposition as good listeners. Mothers’ satisfaction with PMDs’ treatment is significantly (p < 0.05) associated with mothers’ perception of recovery of their child (χ2 = 192.94, df = 4; p < 0.0001; Cramer’s V = 0.7079). However, predicting mothers’ satisfaction with PMDs’ treatment from a knowledge of mothers’ perception of recovery shows a high accord (lambda[A from B] = 0.8727), unlike when predicting mothers’ perception of recovery based on knowledge of mothers’ satisfaction with PMDs’ treatment (lambda[A from B] = 0.4727). Conclusions Mothers’ satisfaction could be the key ‘driver’ of mothers’ health-seeking behaviour and is less likely to be influenced by mothers’ perception of recovery of their child. Therefore, mothers’ negative perception of their child’s recovery may not induce proportionate decline in mothers’ health-seeking behaviour (patronage of PMDs), which might be influenced mainly by mothers’ satisfaction with the positive attributes of PMDs’ personality/practice and sets an important agenda for PHC reforms.

The Voice of History and the Message of the National Curriculum: Recontextualising History to a Pedagogic Discourse for Upper Secondary VET

In the reform by the liberal-conservative government of Swedish upper secondary education in 2011, history was recognized as an important part of citizenship education and was introduced into the curriculum for vocational education and training (VET) tracks. Through the concepts of classification and framing, this article explores the process of constructing the history syllabus for VET. The data consist of archived material from the working group responsible for the history curriculum under the Swedish National Agency for Education. The analysis shows that there are competing discourses concerning the relative emphasis on competencies and skills and concerning the emphasis on contemporary and modern history. Although historians, history teachers and other agents are invited to respond to the content of the curriculum, the respondents have no influence on the knowledge structure of the curriculum, which is controlled by agents of the dominant educational ideology. From a critical perspective, this article suggests that the curriculum reflects the instrumental and neoconservative message of the reform through strong classification and framing and through the emphasis on general abilities and a contemporary history that has a more direct explanatory value to contemporary society.

Pervasive eHealth services a security and privacy risk awareness survey

The human factor is often recognised as a major aspect of cyber-security research. Risk and situational perception are identified as key factors in the decision making process, often playing a lead role in the adoption of security mechanisms. However, risk awareness and perception have been poorly investigated in the field of eHealth wearables. Whilst end-users often have limited understanding of privacy and security of wearables, assessing the perceived risks and consequences will help shape the usability of future security mechanisms. This paper present a survey of the the risks and situational awareness in eHealth services. An analysis of the lack of security and privacy measures in connected health devices is described with recommendations to circumvent critical situations.

Referenciação de crianças com problemas de comunicação e linguagem a partir dos cuidados de saúde primários

Os problemas de comunicação e linguagem (PCL) podem limitar a atividade e participação de um indivíduo ao longo da sua vida. Todavia, a intervenção precoce tem-se provado bastante eficaz nestes casos. Os médicos de família (MF) encontram-se numa posição privilegiada para deteção e referenciação destes problemas em idades precoces. Porém, há evidências de que a sua participação neste processo tem sido reduzida, nomeadamente no que respeita à referenciação para serviços de Intervenção Precoce. Assim, esta investigação pretende compreender qual o papel que os MF consideram ter relativamente a este processo e quais os fatores que podem influenciar a referenciação de crianças com suspeita de PCL. Este estudo teve como base um desenho de investigação descritivo, transversal e observacional. Recorreu-se a um método de amostragem por redes para a distribuição de um questionário On-line. O instrumento foi construído pela autora e é de caráter maioritariamente quantitativo, embora integre uma questão qualitativa de resposta semiaberta. Dos questionários enviados foram devolvidos 55. A resposta semiaberta foi preenchida por 16 dos 55 MF. Os resultados demonstram que a maioria dos MF valoriza bastante ou muito a sua participação na deteção de PCL e considera importante detetar precocemente estes problemas. Para além disso, valorizam bastante ou muito a colaboração em equipa e do terapeuta da fala. A grande parte sente-se influenciada pela preocupação dos pais, pela satisfação com os serviços e com os resultados da Escala de Avaliação de Desenvolvimento de Mary Sheridan Modificada para a referenciação de crianças com PCL. Para além disso, identificam barreiras relacionadas com recursos humanos, serviços, conhecimentos relacionados com o processo de referenciação, burocracia, lentidão do processo e com a atitude dos pais. Considera-se que este estudo pode constituir um ponto de partida para futuras investigações, para a adequação de estratégias institucionais e implementação de práticas que aproximem profissionais e serviços, de forma a melhorar o processo de referenciação de crianças com PCL a partir dos cuidados de saúde primários.

Out with the old, in with the new: A reliable workflow in writing a report on diversity and inclusion

The Diversity Advisory Committee (DAC) will discuss the dynamics of the process of assessing the diversity health at the University of Maryland Libraries. From designing the survey instrument through analyzing the results to the final writing of the report of diversity and inclusion, the committee members will unveil their challenges and achievements in presenting unbiased conclusions from this assessment project. In completing this project, the committee consulted the university’s wisdom, including (1) the College of Information Studies for creating the survey; (2) the Office of Institutional Research, Planning and Assessment (IRPA), and Division of Information Technology (DIT) for analyzing the results; and (3) the Campus Assessment Working Group (CAWG) model for organizing the content of the final report.

Développement d’un questionnaire cognitif bref, le FaCE (The Fast Cognitive Evaluation), selon la modélisation Rasch adapté aux patients avec cancer

Les déficits cognitifs sont présents chez les patients atteints de cancer. Les tests cognitifs tels que le Montreal Cognitive Assessment se sont révélés peu spécifiques, incapables de détecter des déficits légers et ne sont pas linéaires. Pour suppléer à ces limitations nous avons développé un questionnaire cognitif simple, bref et adapté aux dimensions cognitives atteintes chez les patients avec un cancer, le FaCE « The Fast Cognitif Evaluation », en utilisant la modélisation Rasch (MR). La MR est une méthode mathématique probabiliste qui détermine les conditions pour qu’un outil soit considéré une échelle de mesure et elle est indépendante de l’échantillon. Si les résultats s’ajustent au modèle, l’échelle de mesure est linéaire avec des intervalles égaux. Les réponses sont basées sur la capacité des sujets et la difficulté des items. La carte des items permet de sélectionner les items les plus adaptés pour l’évaluation de chaque aspect cognitif et d’en réduire le nombre au minimum. L’analyse de l’unidimensionnalité évalue si l’outil mesure une autre dimension que celle attendue. Les résultats d’analyses, conduites sur 165 patients, montrent que le FaCE distingue avec une excellente fiabilité et des niveaux suffisamment différents les compétences des patients (person-reliability-index=0.86; person-separation-index=2.51). La taille de la population et le nombre d’items sont suffisants pour que les items aient une hiérarchisation fiable et précise (item-reliability=0.99; item-séparation-index=8.75). La carte des items montre une bonne dispersion de ceux-ci et une linéarité du score sans effet plafond. Enfin, l’unidimensionnalité est respectée et le temps d’accomplissement moyen est d’environ 6 minutes. Par définition la MR permet d’assurer la linéarité et la continuité de l’échelle de mesure. Nous avons réussi à développer un questionnaire bref, simple, rapide et adapté aux déficits cognitifs des patients avec un cancer. Le FaCE pourrait, aussi, servir de mesure de référence pour les futures recherches dans le domaine.

Experiences of women in secure care who have been prescribed clozapine for borderline personality disorder

Background: Clozapine is an atypical antipsychotic medicine which can cause significant side-effects. It is often prescribed off-license in severe cases of borderline personality disorder contrary to national treatment guidelines. Little is known about the experiences of those who take clozapine for borderline personality disorder. We explored the lived-experience of women in secure inpatient care who were prescribed clozapine for borderline personality disorder. Findings: Adult females (N=20) participated in audio-taped semi-structured interviews. Transcripts were subject to thematic analysis. The central themes related to evaluation, wellbeing, understanding and self-management; for many, their subjective wellbeing on clozapine was preferred to prior levels of functioning and symptomatology, sometimes profoundly so. The negative and potentially adverse effects of clozapine were explained as regrettable but relatively unimportant. Conclusions: When psychological interventions are, at least initially, ineffective then clozapine treatment is likely to be evaluated positively by a group of women with borderline personality disorder in secure care despite the potential disadvantages.

Towards guidelines for curriculum design and development in English language teacher education in Cambodian higher education institutions

In the current Cambodian higher education sector, there is little regulation of standards in curriculum design of undergraduate degrees in English language teacher education. The researcher, in the course of his professional work in the Curriculum and Policy Office at the Department of Higher Education, has seen evidence that most universities tend to copy their curriculum from one source, the curriculum of the Institute of Foreign Languages, the Royal University of Phnom Penh. Their programs fail to impose any entry standards, accepting students who pass the high school exam without any entrance examination. It is possible for a student to enter university with satisfactory scores in all subjects but English. Therefore, not many graduates are able to fulfil the professional requirements of the roles they are supposed to take. Neau (2010) claims that many Cambodian EFL teachers do not reach a high performance standard due to their low English language proficiency and poor background in teacher education. The main purpose of this study is to establish key guidelines for developing curricula for English language teacher education for all the universities across the country. It examines the content of the Bachelor‘s degree of Education in Teaching English as a Foreign Language (B Ed in TEFL) and Bachelor‘s degree of Arts in Teaching English to Speakers of Other Languages (BA in TESOL) curricula adopted in Cambodian universities on the basis of criteria proposed in current curriculum research. It also investigates the perspectives of Cambodian EFL teachers on the areas of knowledge and skill they need in order to perform their English teaching duties in Cambodia today. The areas of knowledge and skill offered in the current curricula at Cambodian higher education institutions (HEIs), the framework of the knowledge base for EFL teacher education and general higher education, and the areas of knowledge and skill Cambodian EFL teachers perceive to be important, are compared so as to identify any gaps in the current English language teacher education curricula in the Cambodian HEIs. The existence of gaps show what domains of knowledge and skill need to be included in the English language teacher education curricula at Cambodian HEIs. These domains are those identified by previous curriculum researchers in both general and English language teacher education at tertiary level. Therefore, the present study provides useful insights into the importance of including appropriate content in English language teacher education curricula. Mixed methods are employed in this study. The course syllabi and the descriptions within the curricula in five Cambodian HEIs are analysed qualitatively based on the framework of knowledge and skills for EFL teachers, which is formed by looking at the knowledge base for second language teachers suggested by the methodologists and curriculum specialists whose work is elaborated on the review of literature. A quantitative method is applied to analyse the perspectives of 120 Cambodian EFL teachers on areas of knowledge and skills they should possess. The fieldwork was conducted between June and August, 2014. The analysis reveals that the following areas are included in the curricula at the five universities: communication skills, general knowledge, knowledge of teaching theories, teaching skills, pedagogical reasoning and decision making skills, subject matter knowledge, contextual knowledge, cognitive abilities, and knowledge of social issues. Additionally, research skills are included in three curricula while society and community involvement is in only one. Further, information and communication technology, which is outlined in the Education Strategies Plan (2006-2010), forms part of four curricula while leadership skills form part of two. This study demonstrates ultimately that most domains that are directly and indirectly related to language teaching competence are not sufficiently represented in the current curricula. On the basis of its findings, the study concludes with a set of guidelines that should inform the design and development of TESOL and TEFL curricula in Cambodia.