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.

An Empirical Analysis of Performance Impacts Resulting From Conversion to Franchise Operations

Franchising is an important form of organizational control. Possible benefits of franchising include its ability to reduce agency costs that increase with costly monitoring, and provide incentives for the use of local information by onsite managers. However, these benefits may come at a cost, as franchisees may reduce quality by choosing to free ride. While many studies have investigated the reasons for franchising, few studies have documented the impacts of franchising on unit level operating performance. Using time-series data from a number of lodging properties that were converted to franchisee control from company control, this study documents the performance impacts of franchising. The analysis reveals that conversion results in a modest decline in financial performance and an immediate sharp decline in quality.

The Use of Multi-Criteria Decision Analysis in Performing Alternatives Assessment and Comparative Risk Analysis: The Case Study of Codling Moth Pesticides

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

Merging Paradigms: A framework for meeting the goals of sustainable development and corporate sustainability for cruise industry firms

Thesis (Master's)--University of Washington, 2016-06

A Study of Environmental Disclosures in the European Oil and Gas Industry : With Reference to the Global Reporting Initiative

Background and Problem: Sustainability reporting is a growing trend in the society. One of the most exposed industries to environmental matters is the oil and gas industry, which commit to sustainability reporting in order to deal with the industry’s destructive operations. The Global Reporting Initiative (GRI) provides voluntary guidelines in sustainability reporting, which increase transparency for the company’s stakeholders. However, it is controversial that the oil and gas industry put a great effort into sustainability reporting even though the industry is environmentally destructive. This gap is interesting to investigate and will contribute to the academic discussion. Therefore, this thesis will focus on the sustainability reporting in the oil and gas industry and to what extent the industry actually discloses material environmental information about their operations. Purpose: The purpose of this thesis is to examine how the sustainability reporting has changed in the oil and gas industry in Europe. This is performed from a stakeholder perspective. Further, it aims to investigate how oil and gas companies have followed the GRI guidelines and how the reporting has changed over time. Method: A quantitative method is used in order to answer the research questions. The data sample is based on oil and gas companies reporting according to the GRI framework during year 2012 to year 2014. The empirical data is gathered from the studied companies’ environmental category in their sustainability reports. Further, a content analysis technique, with a coding scheme, was set up to interpret and analyse the information. To enable an easy overview of the findings, the relevant data is presented in tables and diagrams. Empirical Findings and Conclusion: The majority of the studied companies have increased their level of compliance in the environmental category. Although, the majority of the companies have increased their reporting, the compliance level differs between the companies. The most reported sectors are the; “Water”, “Biodiversity”, “Emissions”, “Effluents and Waste”, “Compliance”, and “Overall”. Further, the empirical findings show that there is an overall increase in the amount of disclosed information per indicator. The conclusion of this thesis is that the environmental disclosures have increased in the oil and gas industry from year 2012 to 2014.

Product quality and compliance in the pharmaceutical industry

This thesis aims to highlight the importance of a Product Quality & Compliance department in a Pharmaceutical Industry, on the good performance of company's activities and the achievement of their goals and mission. Despite the wide activities performed by this Department, the purpose of this work will be completed by describing only some of their reponsibilities. The tasks described are specifically the ones I have been performing throughout my professional experience at Bluepharma - Pharmaceutical Industry, SA, initiated in June 2012 in the Quality Assurance Department until today in the currently named Product Quality & Compliance department. This thesis is structured into 4 parts. The first chapter is an introduction to this thesis, and includes its context and objectives, followed by a brief overview of the state-of-the art in the pharmaceutical industry, including the market environment, the regulatory environment and quality requirements. A small presentation of the company and the department where were and still are developed my professional activity is also made in this chapter. In the following chapter are described the main tasks performed, the complementary activities and key skills acquired throughout this professional experience. A discussion and conclusion is presented at the end, including an analysis of the reported activities, main difficulties encountered its role and importance in the company performance as well as the skills acquired during this work experience.

A long-term energy efficiency prediction model for the Brazilian automotive industry

According to law number 12.715/2012, Brazilian government instituted guidelines for a program named Inovar-Auto. In this context, energy efficiency is a survival requirement for Brazilian automotive industry from September 2016. As proposed by law, energy efficiency is not going to be calculated by models only. It is going to be calculated by the whole universe of new vehicles registered. In this scenario, the composition of vehicles sold in market will be a key factor on profits of each automaker. Energy efficiency and its consequences should be taken into consideration in all of its aspects. In this scenario, emerges the following question: which is the efficiency curve of one automaker for long term, allowing them to adequate to rules, keep balancing on investment in technologies, increasing energy efficiency without affecting competitiveness of product lineup? Among several variables to be considered, one can highlight the analysis of manufacturing costs, customer value perception and market share, which characterizes this problem as a multi-criteria decision-making. To tackle the energy efficiency problem required by legislation, this paper proposes a framework of multi-criteria decision-making. The proposed framework combines Delphi group and Analytic Hierarchy Process to identify suitable alternatives for automakers to incorporate in main Brazilian vehicle segments. A forecast model based on artificial neural networks was used to estimate vehicle sales demand to validate expected results. This approach is demonstrated with a real case study using public vehicles sales data of Brazilian automakers and public energy efficiency data.

Maurer, Markus: Skill Formation Regimes in South Asia, A Comparative Study on the Path-Dependent Development of Technical and Vocational Education and Training for the Garment Industry (Komparatistische Bibliothek; Bd. 21). Frankfurt am Main: Peter Lang 2011 [Rezension]

Rezension von: Maurer, Markus: Skill Formation Regimes in South Asia, A Comparative Study on the Path-Dependent Development of Technical and Vocational Education and Training for the Garment Industry (Komparatistische Bibliothek; Bd. 21), Frankfurt am Main: Peter Lang 2011 (449 S.; ISBN Skill Formation Regi)

Vision-based tracking for sports performance analysis

With the world of professional sports shifting towards employing better sport analytics, the demand for vision-based performance analysis is growing increasingly in recent years. In addition, the nature of many sports does not allow the use of any kind of sensors or other wearable markers attached to players for monitoring their performances during competitions. This provides a potential application of systematic observations such as tracking information of the players to help coaches to develop their visual skills and perceptual awareness needed to make decisions about team strategy or training plans. My PhD project is part of a bigger ongoing project between sport scientists and computer scientists involving also industry partners and sports organisations. The overall idea is to investigate the contribution technology can make to the analysis of sports performance on the example of team sports such as rugby, football or hockey. A particular focus is on vision-based tracking, so that information about the location and dynamics of the players can be gained without any additional sensors on the players. To start with, prior approaches on visual tracking are extensively reviewed and analysed. In this thesis, methods to deal with the difficulties in visual tracking to handle the target appearance changes caused by intrinsic (e.g. pose variation) and extrinsic factors, such as occlusion, are proposed. This analysis highlights the importance of the proposed visual tracking algorithms, which reflect these challenges and suggest robust and accurate frameworks to estimate the target state in a complex tracking scenario such as a sports scene, thereby facilitating the tracking process. Next, a framework for continuously tracking multiple targets is proposed. Compared to single target tracking, multi-target tracking such as tracking the players on a sports field, poses additional difficulties, namely data association, which needs to be addressed. Here, the aim is to locate all targets of interest, inferring their trajectories and deciding which observation corresponds to which target trajectory is. In this thesis, an efficient framework is proposed to handle this particular problem, especially in sport scenes, where the players of the same team tend to look similar and exhibit complex interactions and unpredictable movements resulting in matching ambiguity between the players. The presented approach is also evaluated on different sports datasets and shows promising results. Finally, information from the proposed tracking system is utilised as the basic input for further higher level performance analysis such as tactics and team formations, which can help coaches to design a better training plan. Due to the continuous nature of many team sports (e.g. soccer, hockey), it is not straightforward to infer the high-level team behaviours, such as players’ interaction. The proposed framework relies on two distinct levels of performance analysis: low-level performance analysis, such as identifying players positions on the play field, as well as a high-level analysis, where the aim is to estimate the density of player locations or detecting their possible interaction group. The related experiments show the proposed approach can effectively explore this high-level information, which has many potential applications.

Comparative performance analysis of drives for induction motors

The asynchronous polyphase induction motor has been the motor of choice in industrial settings for about the past half century because power electronics can be used to control its output behavior. Before that, the dc motor was widely used because of its easy speed and torque controllability. The two main reasons why this might be are its ruggedness and low cost. The induction motor is a rugged machine because it is brushless and has fewer internal parts that need maintenance or replacement. This makes it low cost in comparison to other motors, such as the dc motor. Because of these facts, the induction motor and drive system have been gaining market share in industry and even in alternative applications such as hybrid electric vehicles and electric vehicles. The subject of this thesis is to ascertain various control algorithms’ advantages and disadvantages and give recommendations for their use under certain conditions and in distinct applications. Four drives will be compared as fairly as possible by comparing their parameter sensitivities, dynamic responses, and steady-state errors. Different switching techniques are used to show that the motor drive is separate from the switching scheme; changing the switching scheme produces entirely different responses for each motor drive.

Accessing occupational exposure to fungi in a cork industry

Different forms of fungal diseases affecting the nose and paranasal sinuses are recognized, including invasive and non-invasive fungal rhinosinusitis. Penicillium glabrum complex is associated with respiratory diseases such as suberosis, a typical disease of cork industry workers. In addition, Chrysonilia sitophila has been described as causing occupational asthma, associated to prolonged exposure to high counts of spores. In this study we aimed to access fungal exposure in workers from one cork industry through the mycological analysis of their nasal exudate and the environmental fungal contamination of their surroundings as well.

The analysis and detection of new psychoactive substances in biological matrices

New psychoactive substances (NPSs) have appeared on the recreational drug market at an unprecedented rate in recent years. Many are not new drugs but failed products of the pharmaceutical industry. The speed and variety of drugs entering the market poses a new complex challenge for the forensic toxicology community. The detection of these substances in biological matrices can be difficult as the exact compounds of interest may not be known. Many NPS are sold under the same brand name and therefore users themselves may not know what substances they have ingested. The majority of analytical methods for the detection of NPSs tend to focus on a specific class of compounds rather than a wide variety. In response to this, a robust and sensitive method was developed for the analysis of various NPS by solid phase extraction (SPE) with gas chromatography mass spectrometry (GCMS). Sample preparation and derivatisation were optimised testing a range of SPE cartridges and derivatising agents, as well as derivatisation incubation time and temperature. The final gas chromatography mass spectrometry method was validated in accordance with SWGTOX 2013 guidelines over a wide concentration range for both blood and urine for 23 and 25 analytes respectively. This included the validation of 8 NBOMe compounds in blood and 10 NBOMe compounds in urine. This GC-MS method was then applied to 8 authentic samples with concentrations compared to those originally identified by NMS laboratories. The rapid influx of NPSs has resulted in the re-analysis of samples and thus, the stability of these substances is crucial information. The stability of mephedrone was investigated, examining the effect that storage temperatures and preservatives had on analyte stability daily for 1 week and then weekly for 10 weeks. Several laboratories identified NPSs use through the cross-reactivity of these substances with existing screening protocols such as ELISA. The application of Immunalysis ketamine, methamphetamine and amphetamine ELISA kits for the detection of NPS was evaluated. The aim of this work was to determine if any cross-reactivity from NPS substances was observed, and to determine whether these existing kits would identify NPS use within biological samples. The cross- reactivity of methoxetamine, 3-MeO-PCE and 3-MeO-PCP for different commercially point of care test (POCT) was also assessed for urine. One of the newest groups of compounds to appear on the NPS market is the NBOMe series. These drugs pose a serious threat to public health due to their high potency, with fatalities already reported in the literature. These compounds are falsely marketed as LSD which increases the chance of adverse effects due to the potency differences between these 2 substances. A liquid chromatography tandem mass spectrometry (LC-MS/MS) method was validated in accordance with SWGTOX 2013 guidelines for the detection for 25B, 25C and 25I-NBOMe in urine and hair. Long-Evans rats were administered 25B-, 25C- and 25I-NBOMe at doses ranging from 30-300 µg/kg over a period of 10 days. Tail flick tests were then carried out on the rats in order to determine whether any analgesic effects were observed as a result of dosing. Rats were also shaved prior to their first dose and reshaved after the 10-day period. Hair was separated by colour (black and white) and analysed using the validated LC-MS/MS method, assessing the impact hair colour has on the incorporation of these drugs. Urine was collected from the rats, analysed using the validated LC-MS/MS method and screened for potential metabolites using both LC-MS/MS and quadrupole time of flight (QToF) instrumentation.

Reframing Scottish Football: Strategy and the short-term nature of the football industry.

Despite football being deeply entrenched in Scottish culture it is under-researched from a business perspective. This research develops a conceptual framework that views professional football clubs from a number of different perspectives. It draws on strategic management literature since this views the firm as the intersection between internal competence, customer perception and competition within an industry. A review of previous sports business research highlighted five main themes that were used to create a structure for the analysis: on-field performance, attendance, finance, the playing squad and the manager. These themes were used as frames to view the firms within the industry from a number of different perspectives. Each frame allows a different aspect of the firm to be considered singly in turn and then collectively to develop a deeper understanding of the existing frames in use within the industry. The research is based on a pragmatic philosophy that allows mixed methods to be combined to provide both an objective and subjective view of the industry. The subjective view was drawn from five interviews with senior figures within Scottish professional football. These participants were from a number of different roles and organisations within the industry to provide a balance of experiences. The views were triangulated with a descriptive analysis of secondary data from a number of industry sources to establish patterns within and between these frames. A peer group of six clubs was selected as they competed in the Scottish Premier League in each of the seasons within an eleven-year period (2000-2011). The peer group clubs selected were: Aberdeen, Dundee United, Heart of Midlothian (Hearts), Hibernian, Kilmarnock and Motherwell. By focussing on a small group of clubs with a similar on-field record a broad study across the five frames could be carried out in detail without the findings being influenced by the impact of relegation to a lower division or sustained participation in European football. Within each of the original five frames a number of sub-components were identified and linked to the framework; this expanded the content to reflect the findings of this project. There appeared to be little link between on-field performance and attendance although progress to the later stages of cup competitions allowed clubs to connect with fans who do not regularly attend. The relationship between a club’s income and wage bill should be expanded to include interest repayments since this expenditure can be used to highlight future financial problems caused by increased debt levels. Although all of the interview participants spoke with pride of the players that had progressed from the club’s youth academy to success at the highest level the peer group clubs only produced one player each season that played more than ten matches for the club. Almost half of the players signed from the youth academy left the club without playing for the 1st Team. The importance of the relationship between the manager and club chairman was highlighted, although the speed with which managers were appointed suggests that little consideration was given to this before offering a contract. Once appointed there appeared to be little clarity over the job description and areas of responsibility. Several of the interviewees brought experience from other businesses to football but admitted that short-term decision making and entrenched behaviour made change difficult. The conclusion of the research is that by taking a firm-wide view of the club, longer-term decisions can be taken within football. Player development and supporter relationships were both identified as long-term processes that are impacted by the current short-termism. With greater role clarity for managers and a mixture of short and long-term objectives those involved in the industry are more likely to have opportunities to learn from experience and performance, across the different frames, will improve as a result.

Use of business analysis in beef businesses to direct management practice change for climate adaptation outcomes

Beef businesses in northern Australia are facing increased pressure to be productive and profitable with challenges such as climate variability and poor financial performance over the past decade. Declining terms of trade, limited recent gains in on-farm productivity, low profit margins under current management systems and current climatic conditions will leave little capacity for businesses to absorb climate change-induced losses. In order to generate a whole-of-business focus towards management change, the Climate Clever Beef project in the Maranoa-Balonne region of Queensland trialled the use of business analysis with beef producers to improve financial literacy, provide a greater understanding of current business performance and initiate changes to current management practices. Demonstration properties were engaged and a systematic approach was used to assess current business performance, evaluate impacts of management changes on the business and to trial practices and promote successful outcomes to the wider industry. Focus was concentrated on improving financial literacy skills, understanding the business’ key performance indicators and modifying practices to improve both business productivity and profitability. To best achieve the desired outcomes, several extension models were employed: the ‘group facilitation/empowerment model’, the ‘individual consultant/mentor model’ and the ‘technology development model’. Providing producers with a whole-of-business approach and using business analysis in conjunction with on-farm trials and various extension methods proved to be a successful way to encourage producers in the region to adopt new practices into their business, in the areas of greatest impact. The areas targeted for development within businesses generally led to improvements in animal performance and grazing land management further improving the prospects for climate resilience.

A rewarding experience? Exploring how crowdfunding is affecting music industry business models.

This paper provides an exploratory study of how rewards-based crowdfunding affects business model development for music industry artists, labels and live sector companies. The empirical methodology incorporated a qualitative, semi-structured, three-stage interview design with fifty seven senior executives from industry crowdfunding platforms and three stakeholder groups. The results and analysis cover new research ground and provide conceptual models to develop theoretical foundations for further research in this field. The findings indicate that the financial model benefits of crowdfunding for independent artists are dependent on fan base demographic variables relating to age group and genre due to sustained apprehension from younger audiences. Furthermore, major labels are now considering a more user-centric financial model as an innovation strategy, and the impact of crowdfunding on their marketing model may already be initiating its development in terms of creativity, strength and artist relations.