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Approved for public release; distribution is unlimited / The determination of a system's life distribution usually requires the synthesis of a mixture of system survival modes. In order to alleviate the normal non-trivial calculations, this paper presents the concept of a reliability shorthand. After describing the possible ways a system can survive a mission, the practitioner of this shorthand can use stock formulas to obtain a system's survival function. Then simple insertion of the failure rates of the system's components into the known equations results in the system's reliability. Simple examples show the convenience of this shorthand. The TI-59 is demonstrated to be a useful tool; adequate to implement the methodology. / http://archive.org/details/introductiontore00repi / Lieutenant Commander, United States Navy

Cancer and neurodegeneration are detrimental conditions associated with an inappropriate regulation of cell survival and cell death, causing compromised cells to evade death or excessive death of healthy neurons. The mammalian target of rapamycin complex 2 (mTORC2) has been implicated in the regulation of cell survival by phosphorylating the protein kinase Akt. This is dependent upon the scaffold protein Sin1, a core component of mTORC2. The requirement of Sin1 in cell survival, and in particular in neuronal survival, has not been established due to the early embryonic lethality of mice with a targeted deletion of the Sin1 gene. To circumvent this issue, a novel conditional mouse knockout model was established. The role of Sin1 in regulating cell survival was evaluated in fibroblasts and cortical neurons. The loss of Sin1 significantly affected the phosphorylation and activity of Akt in fibroblasts and caused a reduction in cell survival by potentially inducing premature senescence. In contrast, the loss of Sin1 caused an increase in caspase-independent cell death in cortical neurons. Gene-expression analysis of Sin1 knockout cortical neurons demonstrated an important down-regulation of transcription factors, cytoskeletal proteins and components of signalling pathways involved in neuronal survival, aiding to uncover the mechanism by which Sin1 promotes neuronal survival. Taken together, the results presented in this study show a key role of the scaffold protein Sin1 in regulating neuronal survival.

Every year in the United States, cancer accounts for one in four deaths. As the pool of those who have received diagnoses increases, more individuals can be encountered who have survived a terminal diagnosis or exceeded expected time limits for survival. Perhaps even more extraordinary, many of these consider it the "best thing" that ever happened to them. These are the modern eras' "mythical" heroes; they return bearing maps for our own eventual journeys. This study used a grounded theory research approach to illuminate the phenomenon of terminal diagnosis survivorship as evidenced in the psycho/social/spiritual learning process. The unit of analysis is the psychosocial and spiritual learning process as discovered and developed from three cases of individuals who described being positively transformed after receiving a terminal diagnosis. Three research questions were examined: (a) What are the components (e.g., coping strategies, problem solving techniques, emotion management) of the learning process employed by three cancer patients who have experienced a terminal diagnosis? (b) In what ways did the phenomenal meaning of their lives change as they coped with the trauma of a terminal diagnosis followed by remission persisting a significant time past doctors' predictions? (c) What changes did they make in their lives, viewed from a holistic perspective, including thought processes, healthcare, emotion, spirituality and changes in their social lives? A comparative analysis of tape recorded interviews yielded the data resulting in a six-phase model of terminal diagnosis survivorship delineating a psycho/social/spiritual transformational learning process. Death acceptance emerged as a central organizing construct facilitating transformational changes in those given a terminal diagnosis resulting in a constellation of attitudinal and behavioral change. This model challenges and extends theory in adult learning and post traumatic survival by challenging the heavily rational and cognitive based theories of these fields, emphasizing the importance of emotions, altered states, extrarational experiences and spirituality. This model also explicates the role of denial that can alternatively hamper, facilitate or place on hold movement toward death acceptance, the ultimate transformative agent. Additionally, this model elucidates the importance of holding environments on both sustaining and eliciting transformational and developmental change. / Ph. D.

In this dissertation, I use interview data to answer three questions concerning the deindustrialization of southwest and southside Virginia. First, how have Radford City, Montgomery County, Pulaski County, the City of Martinsville and Henry County been affected by plant closures and mass layoffs at the community level? Second, how have displaced workers and their households been affected by this loss of manufacturing jobs? And third, what survival strategies have displaced workers and their households employed as a result of being displaced? In carrying out this research, I engage with four theoretical discussions: (1) deindustrialization of the US South, (2) the impact of deindustrialization on local communities and economies, (3) the impacts of deindustrialization on workers, and (4) workers' strategies for coping with job loss. I argue that the strategies employed are influenced, shaped, and/ or constrained by regional resources, family structure, and previous experience(s) with job loss due to plant closures and layoffs. The findings from this research suggest that household survival strategies are based on four influential or motivating factors: (1) the presence of a spouse and/or children in the home, (2) having prior experience with being displaced, (3) use of personal networks, and (4) utilization of spouses' knowledge, skills, and abilities. At the community level, there are two major findings. First, there is a level of resilience in the worst affected communities that keeps them moving forward, if at a slower pace than desired. Second, deindustrialization does not affect all manufacturing communities the same way. Local economic profiles, local resources, and past ties to manufacturing matter both in the severity of impacts and the options for rebounding and/ or creating new economic identities. For these reasons and others, it is suggested that future research continue to focus on individual communities and localities which are working to identify good long term solutions to address changes due to large scale economic disruption. / Ph. D.

Indiana University-Purdue University Indianapolis (IUPUI) / The crossing of Kaplan-Meier survival curves presents a challenge when conducting survival analysis studies, making it unclear whether any of the study groups involved present any significant difference in survival. An approach involving the determination of maximum vertical distance between the curves is considered here as a method to assess whether a survival advantage exists between different groups of patients. The method is illustrated on a dataset containing survival times of patients treated with two cancer treatment regimes, one involving treatment by chemotherapy alone, and the other by treatment with both chemotherapy and radiotherapy.

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Survival data was obtained from a regional dialysis clinic. The data was divided into two groups, diabetic and non-diabetic. This data was compared to see if the survival rates of the two groups differed significantly. They were compared using the life-table, Kaplan-Meier and proportional hazards methods. Also a parametric comparison based on the Weibull distribution, was performed. The data of the diabetic patients was further split into adult-onset and juvenile-onset diabetes. These groups were compared using the three non-parametric methods and were found not to be significantly different. Thus the two types of diabetics could be treated as one group when comparing diabetics and non-diabetics. It was found that the non-diabetics had a significantly higher survival rate than the diabetics. The cofactors that were found to influence survival in an adverse way were the presence of diabetes and the age at initial dialysis. / Thesis / Master of Science (MSc)

published_or_final_version / Statistics / Master / Master of Philosophy

Community-onset (CO) methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is an evolving problem, and there is a great need for a reliable method to assess MRSA risk at hospital admission. A new MRSA prediction score classifies CO-pneumonia patients into low, medium, and high-risk groups based on objective criteria available at baseline. Our objective was to assess the effect of initial MRSA therapy on mortality in these three risk groups. We conducted a retrospective cohort study using data from the Veterans Health Administration. Patients were included if they were hospitalized with pneumonia and received antibiotics within the first 48 hours of admission. They were stratified into MRSA therapy and no MRSA therapy treatment arms based on antibiotics received in the first 48 hours. MRSA risk groups were analyzed separately. The primary outcome was 30-day patient mortality. Multivariable logistic regression was used to adjust for potential confounders. A total of 80,330 patients met inclusion criteria, of which 36% received MRSA therapy and 64% did not receive MRSA therapy. The majority of patients were classified as either low (51%) or medium (47%) risk, with only 2% classified as high-risk. In the high-risk group, unadjusted 30-day mortality was lower among patients who received initial MRSA therapy (40% versus 58%; p<0.0001). Likewise, multivariable logistic regression analysis also demonstrated that initial MRSA therapy was associated with a lower 30-day mortality in the high-risk group (adjusted odds ratio 0.57; 95% confidence interval 0.42-0.77). There was no benefit of initial MRSA therapy in the low or medium-risk groups. This study demonstrated improved survival with initial MRSA therapy in high-risk CO-pneumonia patients. The MRSA risk score should not replace clinical judgment, but it might be a useful tool to spare MRSA therapy for only those patients who are most likely to benefit. / text