Mechanical ventilation (MV) therapy has been utilised in the intensive care unit (ICU) for 50 years to treat patients with respiratory illness by supporting the work of breathing, providing oxygen and removing carbon dioxide. MV therapy is utilised by 30-50% of ICU patients, and is a major driver of increased length of stay, increased cost and increased mortality. For patients suffering from acute respiratory distress syndrome (ARDS), the optimal MV settings are highly debated. ARDS patients suffer from a lack of recruited alveoli, and the application of positive end expiratory pressure (PEEP) is often used to maintain recruitment to maximise gas exchange and minimise lung damage. However, determining what level of PEEP is best for the patient is difficult. In particular, it involves a complex trade off between patient safety and ventilation efficacy. Currently, no clinical protocols exist to determine a patient-specific “best” PEEP. Model-based approaches provide an alternative patient-specific method to help clinical diagnosis and therapy selection. In particular, model-based methods can utilise a mix of both engineering and medical principles to create patient-specific models. The models are used for optimising ventilation settings and providing greater physiological insight into lung status than is currently available. Two model-based approaches are presented here. First, a quasi-static, minimal model of lung mechanics is presented based solely on fundamental lung physiology and mechanics. Secondly, a model of dynamic functional residual capacity (dFRC) is developed and presented based on model-based status of lung stress and strain. These models are validated with retrospective clinical data to evaluate the potential of such model-based approaches. Finally, the models are further validated with real time clinical data over a broader spectrum of pressure-volume ranges than prior studies to evaluate the clinical viability of model-based approaches to optimise MV therapy. When validated with real-time clinical trials data, the outputs of the recruitment model provide a range of optimal patient-specific values of PEEP based on different clinically and physiologically derived criteria. The recruitment model is also shown to have the ability to track the disease state of ARDS over time. The dFRC model introduces the PEEP stress parameter, β, which represents a unique population constant. The dFRC model suggests that clinically reasonable estimates of dFRC can be achieved by using this novel value of β, rather than the current, potentially hazardous, methods of deflating the lung to atmospheric pressure. Finally, a third model, combining the principles of recruitment and gas exchange is introduced. The combined model has the ability to estimate cardiac output (CO) changes with respect to PEEP changes during MV therapy. In addition, the model relates the coupled areas of circulation and pulmonary management, as well as linking these MV decision support models to oxygenation based clinical endpoints. A proof of concept is shown for this model by combining two different retrospective datasets and highlighting its ability to capture clinically expected drops in CO as PEEP increases. The model allows valuable cardiovascular circulation data to be predicted and also provides an alternative method and clinical end point by which PEEP could be optimised. The model requires further clinical validation before clinical use, but shows significant promise. The models developed and tested in this research enable rapid parameter identification from minimal, readily available clinical data, and thus provide a novel way of guiding therapy. The models can potentially provide clinicians with information to select an optimal patient-specific level of PEEP using only standard ventilation data, such as pressure-volume curves. In addition, the development of a dFRC stress model provides a unique population constant, β. Overall, the modelling approaches developed and validated in this research provide several novel methods of guiding therapy setting mechanical ventilation parameters and tracking and assess a patient’s lung condition. This research thus creates and provides novel validated methods for improving MV therapy with minimal cost or added invasiveness.

This thesis presents a proof of concept study for the better integration of the electrophysiological and modelling aspects of neuroscience. Members of these two sub-disciplines collaborate regularly, but due to differing resource requirements, and largely incompatible spheres of knowledge, cooperation is often impeded by miscommunication and delays. To reduce the model design time, and provide a platform for more efficient experimental analysis, a rapid iterative model design method is proposed. The main achievement of this work is the development of a rapid model evaluation method based on parameter estimation, utilising a combination of evolutionary algorithms (EAs) and graphics processing unit (GPU) hardware acceleration. This method is the primary force behind the better integration of modelling and laboratorybased electrophysiology, as it provides a generic model evaluation method that does not require prior knowledge of model structure, or expertise in modelling, mathematics, or computer science. If combined with a suitable intuitive and user targeted graphical user interface, the ideas presented in this thesis could be developed into a suite of tools that would enable new forms of experimentation to be performed. The latter part of this thesis investigates the use of excitability-based models as the basis of an iterative design method. They were found to be computationally and structurally simple, easily extensible, and able to reproduce a wide range of neural behaviours whilst still faithfully representing underlying cellular mechanisms. A case study was performed to assess the iterative design process, through the implementation of an excitability-based model. The model was extended iteratively, using the rapid model evaluation method, to represent a vasopressin releasing neuron. Not only was the model implemented successfully, but it was able to suggest the existence of other more subtle cell mechanisms, in addition to highlighting potential failings in previous implementations of the class of neuron.

This study examines the effects of unit-level culture on abusive supervision. Utilizing Baumeister and colleagues' (2000) self-regulatory resource depletion model as an explanatory framework, I argue that aggressive unit-level culture will increase the incidence of abusive supervision, whereas people- and team-oriented unit-level cultures will decrease the incidence of abusive supervision. In line with these arguments, I then examine the degree to which those effects are mediated by ego depletion. In sum, I argue that aggressive unit-level culture will increase, while people- and team-oriented cultures will reduce, the amount of supervisor ego depletion, which then increases the incidence of abusive supervision. Using Hobfoll et al.'s (1990) Social Support Resource Theory, I further argue that the relationship between unit-level culture and ego depletion is moderated by supervisor home social support. I tested my model using a sample of 340 nurses and 52 nursing directors working in a large hospital system in the Southwestern United States. I was unable to demonstrate support for my model as hypothesized. However, I am able to contribute to the literature concerning antecedents to abusive supervision by showing that alternative conceptualization of culture impact abusive supervision. Further, I show that aggressive norms mediate the relationship between aggressive culture and abusive supervision. I also contribute to the literature examining resource depletion in the workplace by demonstrating the buffering role of supervisor home social support on ego depletion. Implications and future directions are discussed.

To effect movement, the central nervous system must appropriately coordinate the activities of pools of motoneurons (MNs), the cells which control muscle fibers. Sources of neural drive are often distributed to many MNs of a pool, and thus can synchronize the activities of targeted MNs. In this thesis, synchronization among MNs is used to investigate the strength, temporal progression, and anatomical distribution of neural drive to the hypoglossal motor nucleus (HMN), which controls muscles of the tongue. The HMN is an ideal target for such an investigation because it processes a host of functionally diverse inputs, such as those related to breathing, speaking, and swallowing. Study 1 characterizes motor unit (MU) synchronization within and across bellies of the human genioglossus (GG) muscle when MUs are activated by cortical drive (during voluntary tongue protrusion) or by automatic, brainstem-mediated drive (during rest breathing). We show that voluntary tongue protrusion synchronizes MU spike timing and firing rates within but not across bellies of the GG, whereas during rest breathing, MU firing rates are moderately synchronized both within and across muscle bellies. Study 2 documents respiratory-related synchronization of MU activities in muscles of the tongue and respiratory pump using an anesthetized rat model. The results of this study indicate that upper airway and respiratory pump MN pools share a low frequency respiratory-related drive, but that higher frequency (>8 Hz) synchronization is strongest in MU pairs of the chest-wall. Finally, Study 3 examines the potential for GG multi-unit and single MU activities to be entrained by cortical input. We show that during voluntary tongue protrusion, cortical oscillations in the 15-40 Hz range weakly synchronize MU population activity, and that EEG oscillations in this range intermittently influence the spike timing of individual GG MUs. These studies are the first to characterize MU synchronization by different sources of neural input to the HMN and establish a broad foundation for further investigation of hypoglossal motor control.

Theoretical models of information storage in the brain have suggested that neurons may undergo an experience-dependent tuning or sharpening of their representations in order to maximize the amount of information that can be stored. Changes in the tuning profiles of neurons have been demonstrated to occur when animals must learn perceptual discriminations, however, whether similar changes occur in the absence of behavioral demands is unclear. To address these questions, the activity of simultaneously recorded medial temporal lobe (MTL) neurons was studied in relation to a passive visual recognition memory task. The structure of this task was such that it allowed for a comparison between novelty related responses as well as tuning properties of individual neurons. A total of 565 well isolated single neurons were recorded. The first contribution of this dissertation is the finding of a dissociation between different medial temporal lobe regions such that neurons in temporal area F (TF), but not perirhinal cortex (PRC) or the hippocampus, show an experience-dependent change in their stimulus selectivity. This finding indicates that tuning of stimulus representations may be an effective mechanism for maximizing information storage in some brain regions. The absence of stimulus tuning in higher level association regions (i.e. TF and PRC) suggests that tuning in these regions may be disadvantageous due to the need to construct unified representations across sensory modalities. A complimentary question to the question of network storage capacity is how networks avoid saturation in the connections between neurons. The second contribution of this dissertation is the finding that there exists a decrease in the magnitude of the short time scale correlations between pairs of neurons; suggesting that networks reduce the number of connections between neurons as a stimulus becomes familiar. Gamma oscillations have been proposed to be the mechanism by which groups of neurons coordinate their activity. However, network coordination has only been indirectly measured. The final contribution of this dissertation is the finding that the magnitude of gamma oscillations is strongly correlated with enhanced magnitude of correlations between neurons.

Background: The amount of time that it takes to get a breast cancer diagnosis is very important to patients. The Ontario diagnostic assessment unit (DAU) is designed to improve the quality and timeliness of care during a breast cancer diagnosis. This study described and examined the association between the length of the diagnostic interval and DAU use in Ontario, Canada. Methods: This was a retrospective cohort study among all breast cancer patients diagnosed between Jan 1st, 2011 and Dec 31st, 2011 in Ontario, Canada. DAU use and diagnostic intervals were described. The association between DAU use and the diagnostic interval was examined separately in a cohort of 2499 screen-detected patients and a cohort of 4381 symptomatic patients. Study data sources included administrative databases available at the Institute for Clinical Evaluative Sciences (ICES) and Cancer Care Ontario (CCO). The diagnostic interval was defined as the time from the index contact to the cancer diagnosis. DAU use was determined based on the payment record within the organized screening program as well as the hospital where patients were diagnosed. Multivariate median regressions were used to control for possible confounders. Results: On average, Ontario breast cancer patients waited 4.6 weeks to be diagnosed. Forty-eight percent were diagnosed in a DAU and 52% were diagnosed in the usual care route. In screen-detected patients, DAUs had a higher rate in meeting national timeliness targets compared to usual care (79.1% vs. 70.2%, p<0.001). DAU use was significantly associated with an 8.3-day decrease in the time to diagnosis (95% CI: 6.5-10.2) after controlling for potential confounders. In symptomatic patients, DAUs also had a higher rate in achieving the Canadian timeliness targets compare to usual care (71.7% vs. 58.1%, p<0.001). DAUs significantly reduced the time to diagnosis by 10 days (95% CI: 7.8-11.9) after controlling for possible confounders. Conclusions: We observed considerable variation in breast cancer diagnostic intervals and DAU use in Ontario. Use of Ontario DAUs was associated with improved diagnostic timeliness for breast cancer patients. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2013-11-18 13:19:03.231

The needs of patients who are nursed on the ICU are becoming more widely recognised and services are beginning to reflect this. However there is little research into how patients who have suffered from a severe and progressive muscular paralysis called Guillain-Barré Syndrome (GBS) experience the disease and subsequent hospitalisation. The purpose of this study was to explore how these patients experience the different aspects of the illness, including an extended period of paralysis and treatment on an ICU. This is intended to expand upon the limited research in this area and identify how the findings can inform clinical practice and future studies. Method: A systematic literature search identified research in relation to the experiences of individuals who had GBS which was utilised to form the basis of the understanding for this study. Very little systematic research has looked at individuals‟ experiences of Guillain-Barré Syndrome whilst ill and their subsequent recovery. A mixed methods study was carried out with the aim of adding to this research. Interpretative Phenomenological Analysis was selected as the method of analysis for Study 1, which involved interviews with seven participants who had experienced GBS severe enough to need treatment on an ICU. This then enabled quantitative questionnaires to be disseminated which asked about individuals‟ levels of anxiety, depression and Post Traumatic Stress symptomatology both retrospectively and following recovery in Study 2. Results: Study1 found that participants experienced GBS as either a slow and frustrating, or as a rapid and scary onset. The main themes that were developed included: the paralysis being viewed as multiple losses, frustration, difficulties associated with communication loss, vulnerability and frightening hallucinations. Study 2 utilised non-parametric analyses of the data and found that participants experienced high levels of anxiety and depression at the onset of GBS and that some continued to experience anxiety, depression and post traumatic symptoms after recovery from GBS. Generally the profile suggests predominantly anxiety problems during the acute onset phase and then predominantly depression at the time of follow-up. Aspects of post traumatic stress were positively correlated with duration of mechanical ventilation which in turn was related to duration of paralysis. This challenged the hypothesis that GBS patients habituate to the experience of paralysis. Conclusion: For some individuals, GBS was experienced as a frightening event, but one that they could draw positive things from. However, for others, GBS was experienced as a traumatic event and some of these people continued to exhibit signs of psychological distress even after recovery. It remains important for staff to feel able to speak about distressing situations with their patients and to signpost them to other psychological services if appropriate.

Class of 2012 Abstract / Specific Aims: The objective of this study is to evaluate and compare clinical outcomes and economic impact involved with the use of beractant (B) compared to poractant (P) for the treatment of respiratory distress syndrome (RDS) in premature neonates admitted to a neonatal intensive care unit. Methods: Patients were included if they were less than 35 weeks gestational age at birth, survived at least 48 hours, and admitted to the neonatal intensive care unit and treated with P or B for RDS. The primary outcome of this study is the change in the fraction of inspired oxygen (FiO2) over the first 48 hours after surfactant administration. Secondary outcomes were the change in oxygen saturation, time spent on mechanical ventilation and continuous positive airway pressure (CPAP), complication occurrence and mortality of the neonates. Main Results: There were a total of 40 neonates whose charts were reviewed (n= 13 and n=27 in the P and B groups respectively). The mean gestational age of the neonates were 29.2+/-2.9 and 28.8+/-2.9 weeks in the P and B groups respectively. The FiO2 was found to not be lower between the P and B groups (35.5+/-22.2 and 42.4+/-24.2, respectively; p=0.379), as well as the O2 saturation (94.6+/-4.6 and 92.3+/-6.1; p=0.194). Significance was also not found for the other clinical or economic outcomes assessed in this study. Conclusions: There was not a significant difference between poractant and beractant in FiO2, O2 saturation, or in the other clinical outcomes evaluated in this study.

The purpose of this research was to compile data from both the consumer and business sectors of the economy in an attempt to determine whether unit price information given to the consumer by a mandatory unit price bill would be justified .

This dissertation examines recidivism for domestic violence offenders under both traditional probation and specialized probation conditions. This research compares recidivism at a traditional probation locality (Riverside Criminal Justice Services) and a specialized domestic violence unit (Chesterfield Community Corrections Services) in order to determine the nature of recidivism at both localities. In addition, the research aims to identify individual risk factors which are statistically associated with recidivism. The research is based on secondary data and draws on offender criminal records generated by the Virginia State Police, as well the extraction of information from probation files at both localities. The multivariate models indicate that a higher degree of recidivism occurs at the specialized domestic violence unit, and that the experimental locality, along with a younger age, are consistently statistically significant predictors for recidivism. Less consistent but still statistically significant risk factors included positive drug tests, higher supervision levels, and unsuccessful probation completion. The implications of these findings, as well as policy recommendations and directions for future research are fully discussed.