Impact of quality improvement tools on the performance of firms using different quality management systems

This study compares the impact of quality management tools on the performance of organisations utilising the ISO 9001:2000 standard as a basis for a quality-management system band those utilising the EFQM model for this purpose. A survey is conducted among 107 experienced and independent quality-management assessors. The study finds that organisations with qualitymanagement systems based on the ISO 9001:2000 standard tend to use general-purpose qualitative tools, and that these do have a relatively positive impact on their general performance. In contrast, organisations adopting the EFQM model tend to use more specialised quantitative tools, which produce significant improvements in specific aspects of their performance. The findings of the study will enable organisations to choose the most effective quality-improvement tools for their particular quality strategy

The Making of Experimental Economics: Witness Seminar on the Emergence of a Field

This book is the transcript of a witness seminar on the history of experimental economics, in which eleven high-profile experimental economists participated, including Nobel Laureates Vernon Smith, Reinhard Selten and Alvin Roth. The witness seminar was constructed along four different topics: skills, community, laboratory, and funding. The transcript is preceded by an introduction explaining the method of the witness seminar and its specific set-up and resuming its results. The participants' contribution and their lively discussion provide a wealth of insights into the emergence of experimental economics as a field of research.

Olmsted, De Bow, and the Weight of Evidence on the American Slave South

Scholarship on the American Slave South generally agrees that John Eliot Cairnes's The Slave Power provided a highly biased interpretation of the functioning and long-term viability of the southern slave economy. Published shortly after the outbreak of the Civil War, its partisanship is partly attributed to its clearly stated goal to shift British support from the secession states to the states of the Union. Thus, it is generally agreed, Cairnes sifted his sources to obtain the desired outcome. A more balanced use of the sources at his possession would have provided a very different outcome. This paper will challenge this general assessment of Cairnes's book by examining in some detail two of Cairnes's most important sources: Frederic Law Olmsted's travelogues on the American Slave South and James D. B. De Bow's compilation of statistical data and essays in his Industrial Resources, etc., of the Southern and Western States (1852-53). By contrasting De Bow's use of statistical evidence with Olmsted's travelogues, my final purpose is to question the weight of evidence on the American Slave South. Cairnes aimed, I will argue, much more to balance the evidence than is generally acknowledged, but it is misleading to think that balancing a wide range of evidence washes out bias if this evidence itself is politically skewed, as is the rule rather than the exception.

Impact of T cell receptor affinity on the molecular mechanisms modulating CD8 T cell signalling and function against NY-ESO-1 tumour antigen

It is well established that cytotoxic T lymphocytes play a pivotal role in the protection against intracellular pathogens and tumour cells. Such protective immune responses rely on the specific T cell receptor (TCR)-mediated recognition by CD8 T cells of small antigenic peptides presented in the context of class-I Major Histocompatibility Complex molecules (pMHCs) on the surface of infected or malignant cells. The strength (affinity/avidity) of this interaction is a major correlate of protection. Although tumour-reactive CD8 T cells can be observed in cancer patients, anti-tumour immune responses are often ineffective in controlling or eradicating the disease due to the relative low TCR affinity of these cells. To overcome this limitation, tumour-specific CD8 T cells can be genetically modified to express TCRs of improved binding strength against a defined tumour antigen before adoptive cell transfer into cancer patients. We previously generated a panel of TCRs specific for the cancer-testis antigen NY-ESO-l,57.165 with progressively increased affinities for the pMHC complex, thus providing us with a unique tool to investigate the causal link between the surface expression of such TCRs and T cell activation and function. We recently demonstrated that anti-tumour CD8 T cell reactivity could only be improved within physiological affinity limits, beyond which drastic functional declines were observed, suggesting the presence of multiple regulatory mechanisms limiting T cell activation and function in a TCR affinity-dependent manner. The overarching goal of this thesis was (i) to assess the precise impact of TCR affinity on T cell activation and signalling at the molecular level and (ii) to gain further insights on the mechanisms that regulate and delimitate maximal/optimized CD8 T cell activation and signalling. Specifically, by combining several technical approaches we characterized the activation status of proximal (i.e. CD3Ç, Lek, and ZAP-70) and distal (i.e. ERK1/2) signalling molecules along the TCR affinity gradient. Moreover, we assessed the extent of TCR downmodulation, a critical step for initial T cell activation. CD8 T cells engineered with the optimal TCR affinity variants showed increased activation levels of both proximal and distal signalling molecules when compared to the wild-type T cells. Our analyses also highlighted the "paradoxical" status of tumour-reactive CD8 T cells bearing very high TCR affinities, which retained strong proximal signalling capacity and TCR downmodulation, but were unable to propagate signalling distally (i.e. pERKl/2), resulting in impaired cell-mediated functions. Importantly, these very high affinity T cells displayed maximal levels of SHP-1 and SHP-2 phosphatases, two negative regulatory molecules, and this correlated with a partial pERKl/2 signalling recovery upon pharmacological SHP-l/SHP-2 inhibition. These findings revealed the putative presence of inhibitory regulators of the TCR signalling cascade acting very rapidly following tumour-specific stimulation. Moreover, the very high affinity T cells were only able to transiently express enhanced proximal signalling molecules, suggesting the presence of an additional level of regulation that operates through the activation of negative feedback loops over time, limiting the duration of the TCR-mediated signalling. Overall, the determination of TCR-pMHC binding parameters eliciting optimal CD8 T cell activation, signalling, and effector function while guaranteeing high antigen specificity, together with the identification of critical regulatory mechanisms acting proximally in the TCR signalling cascade, will directly contribute to optimize and support the development of future TCR-based adoptive T cell strategies for the treatment of malignant diseases. -- Les lymphocytes T CD8 cytotoxiques jouent un rôle prédominant dans la protection contre les pathogènes intracellulaires et les cellules tumorales. Ces réponses immunitaires dépendent de la spécificité avec laquelle les récepteurs T (TCR) des lymphocytes CD8 reconnaissent les peptides antigéniques présentés par les molécules du complexe Majeur de Histocompatibilité de classe I (pCMH) à la surface des cellules infectées ou malignes. La force (ou affinité/avidité) de l'interaction du TCR-pCMH est un corrélat majeur de protection. Les réponses immunitaires sont cependant souvent inefficaces et ne permettent pas de contrôler ou d'éliminer les cellules tumorales chez les patients atteint du cancer, et ce à cause de la relative faible reconnaissance des TCRs exprimés par les lymphocytes T CD8 envers les antigènes tumoraux. Afin de surmonter cette limitation, les cellules T anti-tumorales peuvent être génétiquement modifiées en les dotant de TCRs préalablement optimisés afin d'augmenter leur reconnaissance ou affinité contre les antigènes tumoraux, avant leur ré¬infusion dans le patient. Nous avons récemment généré des cellules T CD8 exprimant un panel de TCRs spécifiques pour l'antigène tumoral NY-ESO-l157.16J avec des affinités croissantes, permettant ainsi d'investiguer la causalité directe entre l'affinité du TCR-pCMH et la fonction des cellules T CD8. Nous avons démontré que la réactivité anti-tumorale pouvait être améliorée en augmentant l'affinité du TCR dans une intervalle physiologique, mais au delà duquel nous observons un important déclin fonctionnel. Ces résultats suggèrent la présence de mécanismes de régulation limitant l'activation des cellules T de manière dépendante de l'affinité du TCR. Le but de cette thèse a été (i) de définir l'impact précis de l'affinité du TCR sur l'activation et la signalisation des cellules T CD8 au niveau moléculaire et (ii) d'acquérir de nouvelles connaissances sur les mécanismes qui régulent et délimitent l'activation et la signalisation maximale des cellules T CD8 optimisées. Spécifiquement, en combinant plusieurs approches technologiques, nous avons caractérisé l'état d'activation de différentes protéines de la voie de signalisation proximale (CD3Ç, Lek et ZAP-70) et distale (ERK1/2) le long du gradient d'affinité du TCR, ainsi que l'internalisation du TCR, une étape clef dans l'activation initiale des cellules T. Les lymphocytes T CD8 exprimant des TCRs d'affinité optimale ont montré des niveaux d'activation augmentés des molécules proximales et distales par rapport aux cellules de type sauvage (wild-type). Nos analyses ont également mis en évidence un paradoxe chez les cellules T CD8 équipées avec des TCRs de très haute affinité. En effet, ces cellules anti-tumorales sont capables d'activer leurs circuits biochimiques au niveau proximal et d'internaliser efficacement leur TCR, mais ne parviennent pas à propager les signaux biochimiques dépendants du TCR jusqu'au niveau distal (via phospho-ERKl/2), avec pour conséquence une limitation de leur capacité fonctionnelle. Finalement, nous avons démontré que SHP-1 et SHP-2, deux phosphatases avec des propriétés régulatrices négatives, étaient majoritairement exprimées dans les cellules T CD8 de très hautes affinités. Une récupération partielle des niveaux d'activation de ERK1/2 a pu être observée après l'inhibition pharmacologique de ces phosphatases. Ces découvertes révèlent la présence de régulateurs moléculaires qui inhibent le complexe de signalisation du TCR très rapidement après la stimulation anti-tumorale. De plus, les cellules T de très hautes affinités ne sont capables d'activer les molécules de la cascade de signalisation proximale que de manière transitoire, suggérant ainsi un second niveau de régulation via l'activation de mécanismes de rétroaction prenant place progressivement au cours du temps et limitant la durée de la signalisation dépendante du TCR. En résumé, la détermination des paramètres impliqués dans l'interaction du TCR-pCMH permettant l'activation de voies de signalisation et des fonctions effectrices optimales ainsi que l'identification des mécanismes de régulation au niveau proximal de la cascade de signalisation du TCR contribuent directement à l'optimisation et au développement de stratégies anti-tumorales basées sur l'ingénierie des TCRs pour le traitement des maladies malignes.

Essays on the Economics of Conflict and Migration

Les conflits civils sont des événements dramatiques qui poussent les individus hors de leurs pays d'origine. Mais si l'émigration était elle-même une force pacificatrice? Dans les deux premiers chapitres, je me suis intéressée à l'impact de l'émigration sur l'incidence des conflits civils dans les pays d'origine. Tout d'abord, je construis un modèle théorique d'équilibre général, dans lequel le niveau de conflit d'équilibre est déterminé par la ratio de combattants dans l'économie. Dans ce modèle, l'émigration décourage les conflits en réduisant les gains d'une rébellion, tout en augmentant le coût d'opportunité des combats. La principale prédiction du modèle est que le conflit diminue avec le niveau du salaire étranger net des coûts de migration. Dans le deuxième chapitre, je teste cette prédiction empiriquement. En utilisant une variable instrumentale, je démontre que l'émigration vers les pays développés diminue l'incidence de guerres civiles dans les pays d'origine. Ces résultats prouvent qu'en ouvrant leurs frontières, les pays d'accueil pourraient contribuer à sauver des vies, aussi bien celles des migrants que celles des habitants restés dans leur pays. De plus, les conflits civils tendent à détruire des sociétés en traumatisant les personnes touchées, augmentant ainsi le risque des conflits futurs. Afin de mieux comprendre ce cercle vicieux et de pouvoir y remédier, le troisième chapitre détermine si les enfants ayant vécu la guerre ont une tendance à être plus violent que des co-nationaux nés après la guerre. L'analyse se concentre sur les demandeurs d'asile en Suisse : Cette population est intéressante puisque l'allocation des demandeurs d'asile entre cantons est aléatoire, ce qui prévient le choix d'un canton avec un taux de criminalité plus élevé. Les résultats démontrent un effet de traumatisme causé par la guerre augmentant ainsi le risque de criminalité dans la vie adulte. Cependant, l'analyse de politiques publiques montre que la mise en place de politiques judicieuses permet d'éviter les conséquences de l'exposition à la guerre. En particulier, en offrant aux nouveaux arrivants l'accès au marché de travail ainsi que des perspectives à long-terme, la Suisse peut éliminer complètement l'effet du traumatisme sur la criminalité.

Studies on the development of spectrophotometric method for the determination of haloperidol in pharmaceutical preparations

A spectrophotometric method based on the formation of ion-pair complex between haloperidol and eriochrome black T (EBT) at pH 1.85 has been described. The formed complex was extracted quantitatively into chloroform and measured at 510 nm. Infra red (IR) studies were performed to confirm the formation of ion-pair complex. Beer's law was obeyed in the concentration range of 2.0-9.0 µg mL-1 with molar absorptivity of 2.67 × 10(4) L mol-1 cm-1. The detection limit was found to be 0.18 µg mL-1. Statistical comparison of the results of the proposed method with those of the reference method shows excellent agreement and indicates no significant difference in accuracy and precision.

Effect of temperature, leaf wetness, and rainfall on the production of Guignardia citricarpa ascospores and on back spot severity on sweet orange

The black spot of citrus (Citrus sp.) is caused by Guignardia citricarpa with ascospore production depending on temperature, leaf wetness, and rainfall. The number of ascospores produced was monitored using a spore trap and climatic factors were recorded using an automated meteorological station of 'Natal' and 'Valencia' sweet orange (Citrus sinensis) orchards in Mogi Guaçu in the state of São Paulo, Brazil, from November 2000 to March 2001. The fruits were bagged to prevent infection and the bags removed from different sets of fruit for one week during each of the 18 weeks of the season in both orchards. Ascospores were produced during the entire experimental period, from spring through summer, primarily after rain events. In both orchards, ascospore production reached a peak in January and February. Ascospore production was related to leaf wetness only in the Natal orange orchard but was not related to total rainfall or temperature in either orchard. Disease was most severe on fruit exposed the 7th, 8th, and 13th weeks after beginning the experiment in both cultivars as well as after the 16th week for 'Natal'. There was a strong relationship between disease severity and total rainfall for both orchards and a weak correlation between temperature and severity in the 'Natal' block only. There was no relationship between severity and leaf wetness or ascospore numbers.

On the potential utilisation of sawdust and wood chip screenings

This work is based on the utilisation of sawdust and wood chip screenings for different purposes. A substantial amount of these byproducts are readily available in the Finnish forest industry. A black liquor impregnation study showed that sawdust-like wood material behaves differently from normal chips. Furthermore, the fractionation and removal of the smallest size fractions did not have a significant effect on the impregnation of sawdust-like wood material. Sawdust kraft cooking equipped with an impregnation stage increases the cooking yield and decreases the lignin content of the produced pulp. Impregnation also increases viscosity of the pulp and decreases chlorine dioxide consumption in bleaching. In addition, impregnation increases certain pulp properties after refining. Hydrotropic extraction showed that more lignin can be extracted from hardwood than softwood. However, the particle size had a major influence on the lignin extraction. It was possible to extract more lignin from spruce sawdust than spruce chips. Wood chip screenings are usually combusted to generate energy. They can also be used in the production of kraft pulp, ethanol and chemicals. It is not economical to produce ethanol from wood chip screenings because of the expensive wood material. Instead, they should be used for production of steam and energy, kraft pulp and higher value added chemicals. Bleached sawdust kraft pulp can be used to replace softwood kraft pulp in mechanical pulp based papers because it can improve certain physical properties. It is economically more feasible to use bleached sawdust kraft pulp in stead of softwood kraft pulp, especially when the reinforcement power requirement is moderate.

Unca Don and Unca Scrooge’s Guide to History. Representations of the Past in the Disney Comics of Don Rosa

This thesis studies the various forms and layers of representations of the past that can be found in the Disney comics of Don Rosa. To stay true to the legacy of renowned comic book artist Carl Barks, Rosa has stopped time in the duck universe to the 1950’s: the decade when Barks created his most noted stories. There is a special feel of historicalness in Rosa’s duck stories, as his characters recall events that occurred in both Rosa’s own stories as well as Barks’. Rosa has shed new light to the past of the characters by writing and illustrating the history of Scrooge McDuck, one of the most beloved Disney characters. Rosa is also adamant that the historical facts used in his stories are always correct and based on thorough research. The methodological tools used in the analysis of the comics come from the fields of comic book studies, film theory, and history culture. Film and comics are recognized by many scholars as very similar media, which share elements that make them comparable in many ways. This thesis utilizes studies on historical film, narrative and genre, which provide valuable insight and comparisons for analysis. The thesis consists of three main chapters, the first of which deconstructs the duck universe in the stories in order to understand how the historicalness in them is created,and which outside elements might affect them, including the genre of Disney comics, publishers, and the legacy of Barks. The next chapter focuses on The Life and Times of Scrooge McDuck series, i.e. the stories which are located in the past. Such stories feature similar representations of history as for example Westerns. They also compress and alter history to meet the restrictions of the medium of comics. The last part focuses on the adventure stories which draw inspiration from for example mythology, and take the characters to strange and mystical, but yet historical worlds. Such treasure-hunting stories show similarity to the action-adventure genre in film and for example their stereotypical representations of foreign cultures. Finally, the chapter addresses the problematic of historical fiction and its capability to write history.

Simulation of structural stress history based on dynamic analysis

Modern machine structures are often fabricated by welding. From a fatigue point of view, the structural details and especially, the welded details are the most prone to fatigue damage and failure. Design against fatigue requires information on the fatigue resistance of a structure’s critical details and the stress loads that act on each detail. Even though, dynamic simulation of flexible bodies is already current method for analyzing structures, obtaining the stress history of a structural detail during dynamic simulation is a challenging task; especially when the detail has a complex geometry. In particular, analyzing the stress history of every structural detail within a single finite element model can be overwhelming since the amount of nodal degrees of freedom needed in the model may require an impractical amount of computational effort. The purpose of computer simulation is to reduce amount of prototypes and speed up the product development process. Also, to take operator influence into account, real time models, i.e. simplified and computationally efficient models are required. This in turn, requires stress computation to be efficient if it will be performed during dynamic simulation. The research looks back at the theoretical background of multibody dynamic simulation and finite element method to find suitable parts to form a new approach for efficient stress calculation. This study proposes that, the problem of stress calculation during dynamic simulation can be greatly simplified by using a combination of floating frame of reference formulation with modal superposition and a sub-modeling approach. In practice, the proposed approach can be used to efficiently generate the relevant fatigue assessment stress history for a structural detail during or after dynamic simulation. In this work numerical examples are presented to demonstrate the proposed approach in practice. The results show that approach is applicable and can be used as proposed.

“THE PATIENT SURVIVED DESPITE THE TREATMENT”. A study of Finnish health policy and New Public Management. Case: The Government Resolution on the Health 2015 public health programme.

Internationally, Finland has been among the most respected countries during several decades in terms of public health. WHO has had the most significant influence on Finnish health policy and the relationship has traditionally been warm. However, the situation has slightly changed in the last 10-20 years. The objectives of Finnish national health policy have been to secure the best possible health for the population and to minimize disparities in health between different population groups. Nevertheless, although the state of public health and welfare has steadily improved, the socioeconomic disparities in health have increased. This qualitative case study will demonstrate why health is political and why health matters. It will also present some recommendations for research topics and administrative reforms. It will be argued that lack of political interest in health policy leads to absence of health policy visions and political commitment, which can be disastrous for public health. This study will investigate how Finnish health policy is defined and organised, and it will also shed light on Finnish health policy formation processes and actors. Health policy is understood as a broader societal construct covering the domains of different ministries, not just Ministry of Social Affairs and Health (MSAH). The influences of economic recession of the 1990s, state subsidy reform in 1993, globalisation and the European Union will be addressed, as well. There is not much earlier Finnish research done on health policy from political science viewpoint. Therefore, this study is interdisciplinary and combines political science with administrative science, contemporary history and health policy research with a hint of epidemiology. As a method, literature review, semi-structured interviews and policy analysi will be utilised. Institutionalism, policy transfer, and corporatism are understood as the theoretical framework. According to the study, there are two health policies in Finland: the official health policy and health policy generated by industry, media and various interest organisations. The complex relationships between the Government and municipalities, and on the other hand, the MSAH and National Institute for Health and Welfare (THL) seemed significant in terms of Finnish health policy coordination. The study also showed that the Investigated case, Health 2015, does not fulfil all necessary criteria for a successful public health programme. There were also several features both in Health 2015 and Finnish health policy, which can be interpreted in NPM framework and seen having NPM influences.

Additional revenue opportunities in pulp mills and their impacts on the kraft process

Although the concept of multi-products biorefinery provides an opportunity to meet the future demands for biofuels, biomaterials or chemicals, it is not assured that its implementation would improve the profitability of kraft pulp mills. The attractiveness will depend on several factors such as mill age and location, government incentives, economy of scale, end user requirements, and how much value can be added to the new products. In addition, the effective integration of alternative technologies is not straightforward and has to be carefully studied. In this work, detailed balances were performed to evaluate possible impacts that lignin removal, hemicelluloses recovery prior to pulping, torrefaction and pyrolysis of wood residues cause on the conventional mill operation. The development of mill balances was based on theoretical fundamentals, practical experience, literature review, personal communication with technology suppliers and analysis of mill process data. Hemicelluloses recovery through pre-hydrolysis of chips leads to impacts in several stages of the kraft process. Effects can be observed on the pulping process, wood consumption, black liquor properties and, inevitably, on the pulp quality. When lignin is removed from black liquor, it will affect mostly the chemical recovery operation and steam generation rate. Since mineral acid is used to precipitate the lignin, impacts on the mill chemical balance are also expected. A great advantage of processing the wood residues for additional income results from the fact that the pulping process, pulp quality and sales are not harmfully affected. For pulp mills interested in implementing the concept of multi-products biorefinery, this work has indicated possible impacts to be considered in a technical feasibility study.

Effect of a single tetanus-diphtheria vaccine dose on the immunity of elderly people in São Paulo, Brazil

Epidemiological data regarding tetanus and diphtheria immunity in elderly people in Brazil are scarce. During the First National Immunization Campaign for the Elderly in Brazil in April 1999, 98 individuals (median age: 84 years) received one tetanus-dyphtheria (Td) vaccine dose (Butantan Institute, lot number 9808079/G). Inclusion criteria were elderly individuals without a history of severe immunosuppressive disease, acute infectious disease or use of immunomodulators. Blood samples were collected immediately before the vaccine and 30 days later. Serum was separated and stored at -20ºC until analysis. Tetanus and diphtheria antibodies were measured by the double-antigen ELISA test. Tetanus and diphtheria antibody concentrations lower than 0.01 IU/mL were considered to indicate the absence of protection, between 0.01 and 0.09 IU/mL were considered to indicate basic immunity, and values of 0.1 IU/mL or higher were considered to indicate full protection. Before vaccination, 18% of the individuals were susceptible to diphtheria and 94% were susceptible to tetanus. After one Td dose, 78% became fully immune to diphtheria, 13% attained basic immunity, and 9% were still susceptible to the disease. In contrast, 79% remained susceptible to tetanus, 4% had basic immunity and 17% were fully immune. Although one Td dose increases immunity to diphtheria in many elderly people who live in Brazil, a complete vaccination series appears to be necessary for the prevention of tetanus.

Effects of isoflavone on the learning and memory of women in menopause: a double-blind placebo-controlled study

Hormone decline is common to all women during aging and, associated with other factors, leads to cognitive impairment. Its replacement enhances cognitive performance, but not all women present a clinical and family or personal history that justifies its use, mainly women with a history of cancer. The aim of this study was to determine whether a daily oral dose of 80 mg of isoflavone extract for 4 months can produce benefits in women with low hormone levels, contributing to improvement in cognitive aspects. The sample comprised 50- to 65-year-old women whose menstruation had ceased at least 1 year before and who had not undergone hormone replacement. The volunteers were allocated to two groups of 19 individuals each, i.e., isoflavone and placebo. There was a weak correlation between menopause duration and low performance in the capacity to manipulate information (central executive). We observed an increase in the capacity to integrate information in the group treated with isoflavone, but no improvement in the capacity to form new memories. We did not observe differences between groups in terms of signs and symptoms suggestive of depression according to the Geriatric Depression Scale. Our results point to a possible beneficial effect of isoflavone on some abilities of the central executive. These effects could also contribute to minimizing the impact of memory impairment. Further research based on controlled clinical trials is necessary to reach consistent conclusions.