Software for Designing Custom Orbital-Craniofacial Implant Plans

Purpose: Custom cranio-orbital implants have been shown to achieve better performance than their hand-shaped counterparts by restoring skull anatomy more accurately and by reducing surgery time. Designing a custom implant involves reconstructing a model of the patient's skull using their computed tomography (CT) scan. The healthy side of the skull model, contralateral to the damaged region, can then be used to design an implant plan. Designing implants for areas of thin bone, such as the orbits, is challenging due to poor CT resolution of bone structures. This makes preoperative design time-intensive since thin bone structures in CT data must be manually segmented. The objective of this thesis was to research methods to accurately and efficiently design cranio-orbital implant plans, with a focus on the orbits, and to develop software that integrates these methods. Methods: The software consists of modules that use image and surface restoration approaches to enhance both the quality of CT data and the reconstructed model. It enables users to input CT data, and use tools to output a skull model with restored anatomy. The skull model can then be used to design the implant plan. The software was designed using 3D Slicer, an open-source medical visualization platform. It was tested on CT data from thirteen patients. Results: The average time it took to create a skull model with restored anatomy using our software was 0.33 hours ± 0.04 STD. In comparison, the design time of the manual segmentation method took between 3 and 6 hours. To assess the structural accuracy of the reconstructed models, CT data from the thirteen patients was used to compare the models created using our software with those using the manual method. When registering the skull models together, the difference between each set of skulls was found to be 0.4 mm ± 0.16 STD. Conclusions: We have developed a software to design custom cranio-orbital implant plans, with a focus on thin bone structures. The method described decreases design time, and is of similar accuracy to the manual method.

Quality Physical Activity Participation for Military Veterans with a Physical Disability

Minimal research has explored what comprises a quality physical activity (PA) participation experience, particularly among military Veterans with a physical disability for whom evidence of the benefits of PA is growing. To address this research gap, this dissertation examines quality PA participation among military Veterans with a physical disability. Manuscript 1 explores the views of Veterans with a physical disability regarding what elements constitute a quality PA experience, and how these elements may be fostered. Eighteen Veterans with various physical disabilities and PA experiences participated in interviews. Four quality elements were identified via thematic analysis: group cohesion, challenge, having a role, and independence and choice. A further three factors (the physical and social environments, and program structure) were identified as precursors for a quality experience. Manuscript 2 explores how PA programs for Veterans with a physical disability are delivered, and how these delivery strategies link conceptually to quality participation. Interviews were conducted with program staff from three PA programs for Veterans, and program documentation collected, to develop an understanding of program delivery strategies. Four strategies with potential links to quality participation were identified through thematic analysis: foster social connections, challenge participants, tailor programs and outcomes to match participant needs, and include knowledgeable coaches and instructors. Manuscript 3 evaluates the participation of Veterans with functional impairments in PA events, and examines the relationships among quality precursors, quality elements, and participation outcomes. Results indicate that program participation did not promote long-term increases in PA indicators. However, an indicator of the quality element belongingness mediated the relationship at particular time-points between coach interpersonal skills and three participation outcomes: family integration, PA intentions, and PA planning. These findings suggest that a quality participation experience created by coaches may positively impact the transition to civilian life, and promote efforts to engage in ongoing PA. Overall, this dissertation contributes towards a greater depth in understanding of the experiences of Veterans with a physical disability in PA programs. The findings begin to provide a foundation for researchers and practitioners aiming to create, deliver, and promote quality PA interventions and programming for Veterans with a physical disability.

Regulation of electrical transmission by protein kinase C in Aplysia bag cell neurons

Electrical synapses are composed of gap junctions, made from paired hemi-channels that allow for the transfer of current from one neuron to another. Gap junctions mediate electrical transmission in neurons, where they synchronize spiking and promote rapid transmission, thereby influencing the coordination, pattern, and frequency of firing. In the marine snail, Aplysia calfornica, two clusters of neuroendocrine bag cell neurons use electrical synapses to synchronize a 30-min burst of action potentials, known as the afterdischarge, which releases egg-laying hormone and induces reproduction. In culture, paired bag cell neurons present a junctional conductance that is non-rectifying and largely voltage-independent. During the afterdischarge, PKC is activated, which is known to increase voltage-gated Ca2+ current; yet, little is understood as to how this pathway impacts electrical transmission. The transfer of presynaptic spike-like waveforms (generated in voltage-clamp) to the postsynaptic cell (measured in current-clamp) was monitored with or without PKC activation. It was found that pretreatment with the PKC activator, phorbol-12-myristate-13-acetate (PMA), enhanced junctional conductance between bag cell neurons. Furthermore, in control, presynaptic action potential waveforms mainly evoked postsynaptic electrotonic potentials at both -60 and -40 mV. However, with PKC activation the presynaptic stimulus consistently elicited postsynaptic action potentials from resting potentials of -40 mV, and would occasionally result in firing from repetitive input at -60 mV. Moreover, to assess whether this enhanced electrical transmission genuinely reflects a greater junctional conductance or a change in postsynaptic responsiveness, a fast-phase junctional-like current was applied to single bag cell neurons. Neurons in PMA always fired action potentials in response to current injection as opposed to control, which were less likely to spike. This outcome did not change when the junctional-like current was artificially enhanced in control conditions. Also, in response to fast- and slow-phase electrotonic potential (ETP) waveforms, Ca2+ current was markedly larger in single PMA-treated neurons. These findings suggest that PKC activation may contribute to afterdischarge fidelity by recruiting postsynaptic Ca2+ current to promote synchronous network firing. Finally, Aplysia gap junction genes (innexins) were transfected into mouse N2A cells and characterized. This revealed a biophysical and pharmacological profile similar to native gap junctions.

Cold acclimation of chill coma mechanisms in the locust CNS

Temperature has profound effects on the neural function and behaviour of insects. When exposed to low temperature, migratory locusts (Locusta migratoria) enter chill coma (neuromuscular paralysis) and can resume normal body functions after returning to normal temperature. Our laboratory has studied phenomena underlying environmental stress-induced comas in locusts and found that they are associated with a sudden loss of K+ homeostasis and also a temporary electrical silence in the central nervous system (CNS). However, the mechanisms underlying chill coma entry and recovery are not well understood, particularly the role of the CNS has not been determined. Here, I investigated neural function during chill coma in the locust by measuring electrical activity in the CNS. As pre-exposure to moderately low temperatures, either chronically (cold acclimation) or acutely (rapid cold hardening; RCH), has been found to improve the insect’s cold tolerance, I also determined cold acclimation and RCH protocols that will improve the locust's cold tolerance and whether these protocols affect neural shutdown during chill coma in the locust. With an implanted thermocouple in the thorax, I determined the temperature associated with a loss of responsiveness (CTmin) in intact male adult locusts. In parallel experiments, I recorded field potential (FP) in the metathoracic ganglion (MTG) in semi-intact preparations to determine the temperature that would induce neural shutdown. I found that acclimation at 10 ˚C and RCH at 4 ˚C reduced chill coma recovery time (CCRT) in intact animal preparations and RCH at 4 ˚C for 4 hours reduced the temperature at neural shutdown in semi-intact preparations. These results suggest that pre-exposure to cold can improve the locust's resistance to chill coma and support the notion that the CNS has a role in determining entry into and exit from chill coma in locusts.

Exploring the Experience of Teachers Working with Exceptional Learners

Regular classroom teachers, who often report that they lack adequate training and resources, increasingly find themselves supporting students with special education needs (Connelly & Graham, 2009). Teachers working in challenging environments can thrive in their role and continue to experience professional growth and passion about their work with students with exceptionalities (Perry, Brenner, Collie, & Hofer, 2015). Thriving is one framework of psychological wellness that can provide insight into the experiences of teachers working with exceptional learners (Spreitzer & Porath, 2014). Chronic stress from occupational demands such as heavy workload and insufficient resources can negatively affect the wellbeing of teachers and lead to poor mental health (Desrumaux et al., 2015). Burnout and compassion fatigue are two constructs of poor mental health that can inform our understanding of teachers’ social and emotional experiences. The purpose of this study was to explore the social and emotional experiences of teachers working with exceptional learners in regular classrooms. The objective of this study was to describe the elements within teachers’ professional roles that they report contribute to their social and emotional experiences understood through the lenses of thriving, burnout, and compassion fatigue. Interviews were conducted with five teachers: one full-time in-service teacher and four teachers who are pursuing graduate studies in education. The theme of thriving emerged as a significant component of the interview with all five participants. All five participants described experiences of vitality and learning as essential to their workplace satisfaction and overall thriving. Although the data from this study did not suggest that participants were experiencing burnout or compassion fatigue, elements of the two constructs did emerge as relevant to the social-emotional experiences of the teachers.

PROLINE-BASED CHIRAL STATIONARY PHASES: INSIGHTS INTO THE MECHANISM OF CHIRAL SELECTIVITY

Proline (Pro) is a unique amino acid that has been examined previously as a potential chiral selector for high-performance liquid chromatography. In recent years, a new class of promising Pro based enantioselective stationary phases has been studied and the longer peptides were found to be competitive with commercial chiral stationary phases (CSPs). Here, we aim to perform a comprehensive examination of a t-butoxycarbonyl- (t-Boc-) terminated monoproline selector. This selector was grafted through an amide linkage to an aminopropyl siloxane-terminated Si (111) wafer and to a silicon atomic force microscopy tip. To ensure a flat, homogeneous overlayer of selectors suitable for force spectrometric measurements, the prepared surfaces were characterized using XPS, AFM and contact angle measurements. Chemical force spectrometry (CFS) has been used to examine the chiral discrimination in our monoproline CSP by measuring the interaction forces between two D- or L-monoproline monolayers in water and in the presence of a series of amino acids in solution to explore the degree to which binding of amino acids impacts self-selectivity. Chemical force titration (CFT) has been used to observe the influence of variations in pH on the binding interaction of proline modified chiral surfaces. Here we aim to explore the connection between side-chain hydrophobicity and differences in the nature of the binding between different ionic forms of amino acids and the t-Boc-Pro interface, and thereby to gain insight into the mechanism of chiral selectivity. The CFS results show several trends for different proline selector/amino acid combinations and indicate that the binding characteristics of amino acid to the proline surface is strongly dependent on the amino acid side chain where hydrophilic side chain amino acids exhibit a selectivity opposite to that seen for those with hydrophobic side chains. The CFT studies also provide valuable insights into interactions between the proline selector and the amino acids under a wide range of pH conditions, indicating that protonated amine groups of alanine and serine are closely involved in the binding mechanism to proline surfaces. On the other hand, the presence of the second carboxylic group in aspartic acid plays an important role while interacting with proline.

CLASHES IN CONFINEMENT: MEN’S GENDERED EXPERIENCES WITH CONFLICT IN CANADIAN PRISONS

This dissertation presents the results of in-depth qualitative interviews with twenty-three formerly imprisoned men regarding their lived experience with prison conflict and the pain of incarceration. The results suggest that prison is a gendered ‘total institution’ (Goffman 1961). The pains that men experience in prison are uniquely gendered in that the deprivations imposed by incarceration– deprivation of autonomy, liberty, goods and services, heterosexual sex, and security (Sykes 1958) – in the reverse, define idealized masculinity as it is currently socially constructed: self-reliance, independence, toughness or invulnerability, material and economic success, and heterosexual prowess. From these shared deprivations emerges a gendered code of conduct that perpetuates a hierarchy among incarcerated men by constructing violent masculinity as a subcultural norm. The results suggest that the gender code in prison represents a set of rules that create opportunities for men to police each other’s gender performance and make claims to masculine statuses. Because status is inextricably tied to survival in this context, many men feel pressured to perform violent masculinities in prison despite privately subscribing to a non-violent sense of self-concept. The results suggest that violence is an expressive and instrumental resource for men in prison. A gender theory of prison violence, methodological findings, theoretical implications, ethical considerations and the short and long term aftermath of violent prison conflict are discussed.

Successful Aging with Illness

In twenty years almost one in four Canadians will be over the age of 65. How successfully these people age will influence their quality of life and contribute to their physical health. Illness and disease are frequent components of aging; however, ‘successful aging’ research normally excludes people with illness. Older people living with illness, even life threatening illness, often self-report a good quality of life and continue to experience psychological well-being and a significant engagement in social life. This dissertation uses a three manuscript approach to examine successful aging among people with illness. The first manuscript employed a scoping review to examine the models used in recent successful aging research, compiling the most frequently used constructs which included: engagement, optimism and/or positive attitude, resilience, spirituality and/or religiosity, self-efficacy and/or self-esteem, and gerotranscendence. The second manuscript utilized data gathered via interviews (online or in person) with people over the age of 65 years living with illness. The majority of these participants reported success in aging; only resilience was predictive in the binomial regression analysis. The third manuscript examined the role of social determinants of health on successful aging. The analysis revealed that disengagement from community-activities showed a significant association with higher self-reported successful aging. The best fitting model for predicting rate of successful aging with illness was a linear combination of participants’ ageism score and community activity score, while controlling for gender and age. When considered together, the results from these three manuscripts suggest that successful aging can be experienced by older adults aging with illness. And that, among these older adults, resilience, community interaction and ageism may all play a part in determining the extent to which aging is experienced as successful. Recommendations include the suggestion that we embrace the idea that people with illness can self-define as successful agers. Further, since some of the associated constructs (e.g. resilience) can be fostered, successful aging could be bolstered by education or programs to build skills along with the usual treatment modalities for the illnesses that co-exist.

Retro-Neoliberalism: Elite Counter-Protest in Latin America, 1940-1975

This research challenges the origin story of neoliberalism in Latin America. Drawing on archival data from the Mont Pèlerin Society and the personal archives of leading but neglected figures in the post-war push to rebuild economic liberalism, I present a historical geography of elite counter-protest that both predates and broadens the generally accepted “birth” of neoliberalism in 1970s Chile. Beginning in the 1940s, Latin American elites found common cause with key figures from economic liberalism’s most radical wing: the Austrian School. While existing literature links the onset of neoliberalism in Chile to the Austrian School, particularly with respect to the School’s influence on the early Mont Pèlerin Society, this dissertation is the first comprehensive inquiry to place the Austrian tradition in the ideational and organizational landscape of Latin America. Embracing a new mission that promised to save the soul of Western civilization, Latin America’s retro-neoliberal leaders collaborated with transnational actors to build a network of Austrian-inspired think-tanks and institutes of higher learning in the region. These organizations, in turn, served as recruiting mechanisms to found the Hispanic quarter of the Mont Pèlerin Society, which was dominated not (as might be assumed) by Chileans, but rather by retro-neoliberal elites from Mexico, Argentina, Guatemala, and Venezuela. By 1975, when scholars began analyzing how a run-of-the-mill economics department had been transformed into a bastion of free-market thinking in Chile, an entire neoliberal university was up and running in Guatemala, exposing all students, regardless of discipline, to the Austrian tradition – the crowning achievement of Latin America’s retro-neoliberal network. Investigating, and accounting for, the development and impact of this initiative sheds new light on the neoliberal landscape in Latin America, and raises important questions for the study of neoliberalism more broadly.

Efficient algorithms for beacon routing in polygons

In a paper by Biro et al. [7], a novel twist on guarding in art galleries is introduced. A beacon is a fixed point with an attraction pull that can move points within the polygon. Points move greedily to monotonically decrease their Euclidean distance to the beacon by moving straight towards the beacon or sliding on the edges of the polygon. The beacon attracts a point if the point eventually reaches the beacon. Unlike most variations of the art gallery problem, the beacon attraction has the intriguing property of being asymmetric, leading to separate definitions of attraction region and inverse attraction region. The attraction region of a beacon is the set of points that it attracts. For a given point in the polygon, the inverse attraction region is the set of beacon locations that can attract the point. We first study the characteristics of beacon attraction. We consider the quality of a "successful" beacon attraction and provide an upper bound of $\sqrt{2}$ on the ratio between the length of the beacon trajectory and the length of the geodesic distance in a simple polygon. In addition, we provide an example of a polygon with holes in which this ratio is unbounded. Next we consider the problem of computing the shortest beacon watchtower in a polygonal terrain and present an $O(n \log n)$ time algorithm to solve this problem. In doing this, we introduce $O(n \log n)$ time algorithms to compute the beacon kernel and the inverse beacon kernel in a monotone polygon. We also prove that $\Omega(n \log n)$ time is a lower bound for computing the beacon kernel of a monotone polygon. Finally, we study the inverse attraction region of a point in a simple polygon. We present algorithms to efficiently compute the inverse attraction region of a point for simple, monotone, and terrain polygons with respective time complexities $O(n^2)$, $O(n \log n)$ and $O(n)$. We show that the inverse attraction region of a point in a simple polygon has linear complexity and the problem of computing the inverse attraction region has a lower bound of $\Omega(n \log n)$ in monotone polygons and consequently in simple polygons.

The Influence of Healed Intrablock Rockmass Structure on the Behaviour of Deep Excavations in Complex Rockmasses

Conventional rockmass characterization and analysis methods for geotechnical assessment in mining, civil tunnelling, and other excavations consider only the intact rock properties and the discrete fractures that are present and form blocks within rockmasses. Field logging and classification protocols are based on historically useful but highly simplified design techniques, including direct empirical design and empirical strength assessment for simplified ground reaction and support analysis. As modern underground excavations go deeper and enter into more high stress environments with complex excavation geometries and associated stress paths, healed structures within initially intact rock blocks such as sedimentary nodule boundaries and hydrothermal veins, veinlets and stockwork (termed intrablock structure) are having an increasing influence on rockmass behaviour and should be included in modern geotechnical design. Due to the reliance on geotechnical classification methods which predate computer aided analysis, these complexities are ignored in conventional design. Given the comparatively complex, sophisticated and powerful numerical simulation and analysis techniques now practically available to the geotechnical engineer, this research is driven by the need for enhanced characterization of intrablock structure for application to numerical methods. Intrablock structure governs stress-driven behaviour at depth, gravity driven disintegration for large shallow spans, and controls ultimate fragmentation. This research addresses the characterization of intrablock structure and the understanding of its behaviour at laboratory testing and excavation scales, and presents new methodologies and tools to incorporate intrablock structure into geotechnical design practice. A new field characterization tool, the Composite Geological Strength Index, is used for outcrop or excavation face evaluation and provides direct input to continuum numerical models with implicit rockmass structure. A brittle overbreak estimation tool for complex rockmasses is developed using field observations. New methods to evaluate geometrical and mechanical properties of intrablock structure are developed. Finally, laboratory direct shear testing protocols for interblock structure are critically evaluated and extended to intrablock structure for the purpose of determining input parameters for numerical models with explicit structure.

Keeping Variables within Bounds: Using Information between Observations

This research develops an econometric framework to analyze time series processes with bounds. The framework is general enough that it can incorporate several different kinds of bounding information that constrain continuous-time stochastic processes between discretely-sampled observations. It applies to situations in which the process is known to remain within an interval between observations, by way of either a known constraint or through the observation of extreme realizations of the process. The main statistical technique employs the theory of maximum likelihood estimation. This approach leads to the development of the asymptotic distribution theory for the estimation of the parameters in bounded diffusion models. The results of this analysis present several implications for empirical research. The advantages are realized in the form of efficiency gains, bias reduction and in the flexibility of model specification. A bias arises in the presence of bounding information that is ignored, while it is mitigated within this framework. An efficiency gain arises, in the sense that the statistical methods make use of conditioning information, as revealed by the bounds. Further, the specification of an econometric model can be uncoupled from the restriction to the bounds, leaving the researcher free to model the process near the bound in a way that avoids bias from misspecification. One byproduct of the improvements in model specification is that the more precise model estimation exposes other sources of misspecification. Some processes reveal themselves to be unlikely candidates for a given diffusion model, once the observations are analyzed in combination with the bounding information. A closer inspection of the theoretical foundation behind diffusion models leads to a more general specification of the model. This approach is used to produce a set of algorithms to make the model computationally feasible and more widely applicable. Finally, the modeling framework is applied to a series of interest rates, which, for several years, have been constrained by the lower bound of zero. The estimates from a series of diffusion models suggest a substantial difference in estimation results between models that ignore bounds and the framework that takes bounding information into consideration.

Sucrose Bingeing Reduces the Reward Value of Sucrose

Binge eating occurs primarily on highly palatable food (PF) suggesting that the reward value of food has an important role in this behaviour. Bingeing also leads to reward dysfunction in rats and humans. The rewarding effect of binge eating may involve opioid mechanisms as opioid antagonists reduce PF consumption in animals that binge eat and binge eating produces neuroadaptations of opioid receptors in rodents. We tested this hypothesis by using the conditioned place preference (CPP) paradigm. First we established a sucrose CPP in male and female Long-Evans rats (n=8 for each group) using 1%, 5%, 15%, or 30% sucrose solution. Next, rats underwent the sucrose bingeing model in which separate groups of rats (n=8 for each group) received 12hr and 24hr access to 10% sucrose solution and chow, 12hr access to 0.1% saccharin solution and chow, or 12hr access to chow only every day for 28 days. Immediately following these sessions, rats were conditioned and tested in the CPP paradigm using a 15% sucrose solution. Finally, we examined whether the sucrose bingeing model altered morphine reward in female rats. Rats (n=8 for each group) received 12hr and 24hr access to 10% sucrose solution and chow every day for 28 days. Immediately following this access period, rats were conditioned to morphine (6mL/kg) or saline solution in the CPP paradigm and tested for a CPP. In all experiments, rats drank more sucrose solution than water during conditioning sessions. Male rats did not develop a CPP to any concentration of sucrose solution and females developed a CPP to 15% sucrose solution only. Following the sucrose bingeing protocol, sucrose CPP was attenuated in male rats that binged on sucrose and in all female rats. Sucrose bingeing in females did not affect the development of a CPP to morphine. These results suggest that sucrose consumption and sucrose CPP are measures of different psychological components of reward. Furthermore, sucrose bingeing reduces the rewarding effect of sucrose, but not morphine, suggesting that opioid reward is still intact.

Weight Loss in the Chiropractic Profession

Background: Excess weight places a significant burden on health. Clinical practice guidelines advise healthcare professionals to provide weight management interventions to patients with overweight and obesity. Chiropractic practice may provide a unique opportunity to deliver weight management interventions to those with overweight and obesity. However, little has been done to address overweight and obesity within the chiropractic profession. Identifying the extent of this evidence-practice gap in chiropractic practice is the first step in addressing this issue. Objectives: This thesis was to assess the clinical practices of weight loss provided by chiropractors. The primary objectives were to 1) determine the prevalence of overweight and obesity in the adult patient population that sought chiropractic care, 2) describe the frequency and distribution of chiropractor directed weight management intervention, 3) identify associations between chiropractor directed weight management interventions and specific patient-level and chiropractor-level variables, and 4) examine the interaction between patient weight and comorbid conditions and whether chiropractors offered weight management interventions. Methods: Data from the Ontario Chiropractic Observational and Analysis Study was used (N = 42 chiropractors, N = 3523 patient encounters). Multilevel logistic regression was performed. Patient-level as well as chiropractor-level variables were investigated and associations with weight management provided by chiropractors were identified. Results: The majority of patients who sought chiropractic were overweight or obese (61.2%). Weight loss was provided to only 5.4% of patients. Chiropractors who graduated between 1995 and 2005 (OR: 0.02, 95% CI: 0.00 - 0.13) or prior to 1995 (OR: 0.08, 95% CI: 0.01 - 0.42) provided weight management significantly less than chiropractors who graduated between 2005 and 2014. No significant interaction was observed between patient adiposity and comorbid conditions with chiropractors directed weight loss. Conclusion: The majority of patients who seek chiropractic care are overweight and obese. Chiropractors are in a unique position to help improve patient health through offering weight management. However, this opportunity has not been fully realized by the chiropractic profession.

Salmonella Enterica serovar Typhimurium Infection in Mouse Pregnancy

Salmonella are Gram-negative, intracellular food-borne pathogens that cause pregnancy complications. In pregnant mice, Salmonella enterica serovar Typhimurium (S.Tm) infection results in placental bacterial replication, inflammation, necrosis, and fetal loss by unknown mechanisms. Necroptosis, or programmed necrosis mediated by RIPK3 (receptor-interacting protein kinase 3), an inflammatory cell death pathway, is implicated in the pathogenesis of S.Tm in non-pregnant mice. This goal of this thesis was to investigate the role of necroptosis in the pathogenesis of S.Tm infection during mouse pregnancy. I hypothesized that elimination of the key necroptotic cell death protein RIPK3 would decrease placental inflammation and trophoblast cell death, and increase conceptus survival compared to controls. Mice expressing a functional Slc11a1 (encodes the natural resistance-associated macrophage protein 1, NRAMP1) gene with or without RIPK3 function (Ripk3-/-Slc11a1+/+ compared to Slc11a1+/+) were infected with 103 S.Tm by tail vein injection on gestational day (GD) 12. Mice were euthanized on GD 14 (48h post-infection) or GD 15 (72h post-infection) and implantation sites (IS) and maternal serum were harvested for analyses. In nearly all challenged mice (except one outlier), S.Tm were detected in most IS within a litter but there was limited immune cell infiltration, placental damage or cell death in Slc11a1 competent mice regardless of Ripk3 gene deletion. Maternal serum cytokine analyses confirmed lack of maternal immune responses to S.Tm infection. IS amongst the litter of a single dam (Ripk3-/-Slc11a1+/+ at 72h postinfection) displayed heavy but not universal placental S.Tm infection of decidual tissues and spongiotrophoblast, associated with elevated maternal serum pro-inflammatory cytokines. S.Tm infection of the fetal yolk sac (YS) was observed in 54.5% of IS from this dam. YS infection was confirmed in archival samples in mice expressing Ripk3 with intact Slc11a1 and in mice lacking functional Slc11a1. In Slc11a1 incompetent mice, S.Tm were detected in placental labyrinthine trophoblast. Based on the available data, this thesis suggests that Ripk3 and necroptosis have no significant roles in either promotion or prevention of progressive Salmonella infection during mouse pregnancy. It also provides pilot data that NRAMP1 controls placental localization and lethality due to YS infection.