Evolutionary game theory tries to explain the emergence of stable behaviors observed in human and animal societies. Prominent examples of such behaviors are cooperative and conformist behaviors. In the first part of the thesis, we develop a model of indirect reciprocity with institutional screening to study how institutions may promote cooperative behavior. We show that cooperation can emerge if screening institutions are sufficiently reliable at identifying cooperators. The second part presents a large-population learning model in which individuals update their beliefs through time. In the model, only one individual updates his beliefs each period. We show that a population, playing a game with two strategies, eventually learns to play a Nash equilibrium. We focus on coordination games and prove that a unique behavior arises both when players use myopic and perturbed best replies. The third part studies the payoff calculation in an evolutionary setting. By introducing mutual consent as a requirement for game play, we provide a more realistic alternative way to compute payoffs. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Manuscript. Paper 3: Manuscript.</p>

The 5-year survival rate for ovarian cancer is only 45% largely due to lack of effective screening methods. Current methods include palpation, transvaginal ultrasound, and the CA-125 blood test. Finding disease reliably and at an early stage increase survival to 92%. We have designed and built a 0.7 mm endoscope for the early detection of ovarian cancer. Inserted transvaginally through the working channel of a hysteroscope, the falloposcope creates a minimally invasive procedure for the screening of high risk women. To improve the ease-of-use and safety of falloposcope deployment, we are working to create an everting balloon. Currently, the falloposcope would require a skilled user to operate due to the challenging anatomy of the fallopian tubes - a small opening from the uterus (< 1 mm), tortuous path, and delicate lumenal features. A balloon delivery system would gently open the fallopian tube and guide the falloposcope down the center of lumen. We show balloon design and discuss integration with the falloposcope prototype. We test possible mechanical damage to the tissue due to scraping, puncture, or overstretching. Successful introduction of the everting balloon to simplify falloposcope delivery could expand screening beyond specialized centers to smaller clinical locations.

Rising rates of obesity among children have become one of the most pressing issues in modern public health. Childhood obesity threatens both the mental and physical well-being of children. Attempts to halt the rise in obesity take many forms, but one of them is the recent implementation of a programme of measurement of primary children at reception and in year 6, with results being fed back to parents. This National Child Measurement Programme (NCMP) is controversial and has been criticised in some quarters as unethical, in being a form of screening programme with no clear or effective interventions available for those detected as having a problem. Study aims and objectives The main aim of the study was to explore the relationship between weight status and children’s mental wellbeing, especially in the context of the NCMP. Within this overall aim, key specific objectives of the study were: i) to investigate the association between weight status of 10-11 year old school children and their mental well-being; ii) to assess the impact on the mental wellbeing of children, of participating in the NCMP; and iii) to collect information about parents’/guardians’ and children’s reaction to the NCMP, with particular interest in identifying whether parents/guardians and their children found the feedback useful in moving towards the adoption of a healthy lifestyle. Methods The study was undertaken in primary schools in the catchment area of Gateshead Primary Care Trust (PCT). The overall study used a mixed methods study design. The study involved administering a questionnaire prior to NCMP measurement to a total sample of 264 children, sampled using a proportionate stratified random sampling technique. One-to-one semi-structured interviews were also conducted post measurement with 21 children purposively sub-sampled from the larger group, and with 16 parents/guardians. Results Prior to measurement, most children misclassified their weight status. About 1 in 10 children who were of ideal weight perceived themselves as overweight. Over three quarters of overweight children perceived themselves to be of ideal weight. There was no significant relationship between any of the indicators of mental wellbeing and actual weight status of children. However, there was very strong evidence for a Preface xxv significant relationship between perceived weight status and mental wellbeing among children. Seven major themes emerged from the post measurement interview data, but perhaps the most intriguing was the cycle of emotional reaction of families to the NCMP and weight feedback. Discussion The reactions of parents/guardians whose children are indicated to have weight problems follow a sequence of behaviours ranging from shock, disgust with the programme, through denial and self-blame to acceptance, worry and help seeking. Reasons for these responses relate in many cases to the way the weight problem is portrayed to the parents. While health authorities are keen to portray this problem as a medical one, parents/guardians see it as social one. The roots of overeating and lack of exercise are seen as lying in the complex social and cultural milieu in which this sample of people live. Consequently, associating this problem in feedback letters with dangerous diseases like cancer, and advising parents to visit GPs to resolve child weight issues, seems inappropriate to the recipients and causes controversy and anger. Conclusion The NCMP’s routine feedback could potentially induce families into the state of readiness to change lifestyle behaviours; however, given the reactions described in this study, it seems critical to avoid placing blame on individuals but rather to acknowledge the influence of the environment surrounding families and to provide non-medical support aimed at bringing families on board to support interventions for combating child weight problems.

"Mémoire présenté à la Faculté des études supérieures en vue de l'obtention du grade de maîtrise en droit (LL.M.) option Droit, biotechnologies et société" / Le diagnostic et le dépistage prénatals ont été créés pour tenter de diminuer, et parfois même enrayer, les inquiétudes qui habitent les parents, et tout particulièrement la femme, dans la période d'attente qu'est la grossesse. Par contre, la science évolue rapidement. Les nouvelles technologies dans le domaine prénatal s'accumulent sans que nous ayons le temps d'en fixer les limites. Il nous apparaît donc primordial de nous pencher sur la problématique de l'encadrement normatif du diagnostic et du dépistage prénatals, afin de comprendre les dilemmes auxquels sont confrontés les différents acteurs. Notre recherche se concentre sur le dépistage par analyse de sérum maternel, une technique de dépistage prénatal. Or, cette technique présente un faible degré de fiabilité. De nombreuses questions éthiques découlent donc de cette pratique. Dans le cadre de notre travail de recherche, nous analysons les enjeux éthiques qui entourent l'utilisation de ce dépistage, puisque les normes éthiques peuvent exercer une certaine influence sur la pratique médicale. De plus, suite à nos recherches, nous avons pu constater que la pratique du dépistage par analyse de sérum maternel est très différente d'un pays à l'autre, et même, d'une région à l'autre dans un même pays. Cette disparité ne s'observe pas uniquement dans la pratique, mais également au niveau des normes juridiques et professionnelles encadrant cette pratique. De plus, en ce qui a trait à l'application des instruments normatifs, selon le pays dans lequel on se trouve, les cours de justice ne traitent pas de la même façon les actions fondées sur une naissance préjudiciable ainsi que celles fondées sur une vie préjudiciable, qui sont directement reliées au diagnostic et au dépistage prénatals. Il est donc intéressant d'effectuer une comparaison entre la pratique et l'encadrement normatif (juridique, professionnel, jurisprudentiel et éthique) du dépistage par analyse de sérum maternel. Notre travail de recherche a donc pour but de proposer quelques recommandations au sujet de l'attitude à adopter au Québec en regard du dépistage par analyse de sérum maternel, et même du diagnostic prénatal dans son ensemble. / Prenatal diagnosis and screening methods were created in an attempt to decrease, and even to eliminate, the worries of parents, especially those of the mother, during the waiting period of pregnancy. However, science evolves rapidly. New technologies in the prenatal field accumulate without giving us the time to set their boundaries. It therefore seems primordial to consider the issues surrounding the legal framework of prenatal diagnosis and screening methods in order to understand the dilemmas which face the different actors in this field. Our research foc uses on maternaI serum screening, one of the prenatal screening techniques. Indeed, this screening method is not very reliable. Actually, many ethical questions stem from this practice. In our research project, we analyze the ethical issues that emerge from the use of this screening method, since ethical nonns may exert a certain influence on medical practice. Furthennore, according to our findings, we have been able to recognize that maternaI serum screening varies from one country to another, and even from one region to another within the same country. This disparity is not only observed in practice, but it is also seen at the level of legal and professional nonns providing the current framework for this method. In addition, with regards to the application of existing nonnative 1Ools, according to the country considered, the courts of justice do not treat in the same fashion wrongful birth c1aims and wrongfullife c1aims, both unfortunate events directly related to prenatal diagnosis and screening. Therefore, it is interesting to compare maternaI serum screening on the level of what occurs in actual practice versus what is provided by the legal, professional, jurisprudential and ethical nonns in the field. The goal of our research is to propose a few recommendations on the attitude that should be adopted in Quebec concerning maternaI serum screening, and even prenatal diagnosis in general.

Type-2 diabetes is a nationally growing health concern. Previous literature has implicated that vitamin D deficiency and type-2 diabetes are interconnected. At this time there are no guidelines in place to guide the evaluation or treatment of vitamin D deficiency in type-2 diabetic patients. In order to create up to date guidelines for the treatment and evaluation of vitamin D deficiency in type-2 diabetic patients an integrative literature review was conducted using EMBASE, PubMed, and CINAHL. The literature review resulted in 44 articles that met the inclusion and exclusion criteria. The literature review resulted in the creation of five clinical recommendations. The most significant change to current clinical standards includes screening all type-2 diabetic patients for vitamin D deficiency. Vitamin D supplementation is not recommended for use in treating type-2 diabetes, diabetic complications, or preventing the progression from prediabetes to diabetes. However, type-2 diabetic patients with vitamin D deficiency should be treated with vitamin D supplementation to improve indirect health outcomes and prevent morbidity and mortality.

Telemedicine offers an alternative referral strategy for fetal cardiology but is currently only used for ‘high-risk’ pregnancies. A case-study of a cost-consequences analysis comparing telemedicine to direct referral to a perinatal cardiologist is initially presented, which highlights that for high risk women for whom telemedicine was considered no cardiac anomalies were missed using either referral method. In the light of a review of the literature on the economics of telemedicine, three of the key methodological issues (of selection bias, of patient costs and using quality-adjusted life years (QALYs)) are explored to demonstrate how the case study analysis could be improved. Pregnant women were selected for referral based on their characteristics and risk factors; thus the cost and effects for the two groups may have been biased. Various methods identified in the literature are applied to the case study to reduce selection bias, but the analysis presented is unable to determine which method is best, given a number of limitations including the small sample size. The analysis is extended to include estimated total patient costs. However, when patient costs are added to the total costs of pregnancy, they did not substantially increase the overall cost. The results presented provide a guideline for future researchers and pregnant women of the likely costs during pregnancy. Given that the majority of missed cardiac anomalies were amongst low risk women, a decision analytical model is developed looking at the lifetime costs and QALYs of introducing telemedicine screening for pregnant women whose unborn babies are at a low risk of congenital heart disease. The analysis shows that offering telemedicine to all low risk women is the dominant strategy. The thesis demonstrates, within the constraints of existing data, that it would be cost-effective to provide telemedicine as part of an antenatal screening programme for all low risk women, and this would help prevent future ‘missed anomalies’.

Since the tragedy of the drug Thalidomide® in the late 1950 to early 1960’s, chirality has been recognized as an important aspect that must be controlled in the drug development process in the pharmaceutical industry. Since then, there has been a considerable movement towards single enantiomer drugs. This demand has presented many challenges for the synthetic organic chemist. Chiral catalysts offer one solution to this problem, as they afford the unique ability to preferentially synthesize one enantiomer. Unfortunately, the design of new chiral catalysts is often empirical, with luck and trial and error necessary due to factors that govern enantioselectivity. Therefore, it would be highly beneficial to develop a method that is capable of screening multiple chiral catalysts early in the catalyst development cycle. Using a modified ion-trap mass spectrometer, the chiral environment of various chiral catalysts may be examined, free from solvent and ion-pairing affects. Thus, the catalyst’s inherent asymmetric environment (enantioselectivity) may be probed using simple chiral molecules, including alcohols, ethers, and epoxides of various steric demands. Using these probes, various C2-symmetric bis-oxazolines and di-imines catalysts were examined. Use of the binaphthyl-based diamine, BINAM, condensed with various 3,5-disubstituted benzaldehydes, provided selectivity close to the privileged catalyst, bis-oxazoline. In general, the chiral probes 1-phenyl-2-propanol, 1-mehtoxyethylbenzene, and styrene oxide offer the best look at the catalyst’s enantioselectivity potential. With the use of the ion-trap mass spectrometer as a mass filter, the purity of the catalyst is not paramount, thus, multiple catalysts may be screened simultaneously, with the constraint that the catalysts must be of different m/z. This thesis presents results found during the exploration of various C2 and C1-symmetric chiral catalysts, in the development of the new chiral screening method utilizing various chiral probes.

Despite strong evidence that screening for Colorectal cancer (CRC) can reduce cancer incidence and mortality, screening adherence remains low. Racial differences in CRC incidence and mortality are well documented in the literature. Racial differences in CRC screening use remain mixed with most studies using race as an independent variable and focusing on racial differences in CRC screening rates. Few studies have examined correlates of CRC screening use, stratifying by race. The purpose of this study was to determine if there are racial differences in correlates of CRC screening, using the Health Belief Model as the theoretical framework. Data analyzed in this study came from the 2003 Health Information National Trends Survey (HINTS) of the National Cancer Institute. White (n=1988) and non-white (562) respondents age ≥50 years, without a history of cancer were interviewed by phone. Multivariable logistic regression was used to identify correlates of FOBT and endoscopy adherence stratified by race and screening test. Independent variables included age, gender, education, income, insurance status, regular care visit frequency, perceived risk of CRC, family history of cancer, CRC knowledge, cancer worry, perceptions of screening benefits, and perceptions of expense as a barrier. Predictors of adherence to FOBT for whites included being older and having at least 1 regular car visit. Predictors of FOBT adherence for non-whites included having health insurance. Endoscopy adherence for whites was significantly associated with being older, being female, and agreeing with perceptions of benefits to CRC screening. Predictors of endoscopy adherence for non-whites included being older, and disagreeing with perceptions of benefits to CRC screening. Such differences, if confirmed in future studies, may inform race-specific interventions to increase CRC screening utilization.

Cervical cancer is the second most common type of cancer in women worldwide. Because cervical cancer is usually asymptomatic until the disease is in its advanced stages, cervical screening is of central importance towards combating cervical cancer. Alternative screening strategies are evaluated from an economic point of view through cost-effectiveness analysis. In the literature however, studies perform cost-effectiveness analysis on a limited number of de facto or predetermined screening policies. At present, no attempt has been made to construct efficient screening strategies through optimization, before cost-effectiveness analysis is applied. In this study simulation optimization is used to construct efficient screening strategies for cervical cancer by properly timing the screenings. The constructed strategies are highly cost-effective when a small number of lifetime screenings is available, and are more cost-effective than screening strategies used in practice or considered in the literature so far, indicating the value of optimal timing for other screened diseases as well.

Cheng and Wu (2001) introduced a method for response surface exploration using only one design by using a 3-level design to first screen a large number of factors and then project onto the significant factors to perform response surface exploration. Previous work generally involved selecting designs based on projection properties first and aliasing structure second. However, having good projection properties is of little concern if the correct factors cannot be identified. We apply Jones and Nachtsheim’s (2009) method for finding optimal designs with minimal aliasing to find 18, 27, and 30-run designs to use for single-step screening and optimization. Our designs have better factor screening capabilities than the designs of Cheng and Wu (2001) and Xu et al. (2004), while maintaining similar D-efficiencies and allowing all projections to fit a full second order model.