The effects of manipulations of Cs duration on blocking.

Thesis (M.S.

Adherence to Nutrition and Physical Activity Cancer Prevention Guidelines and Development of Colorectal Adenoma.

Adherence to the American Cancer Society's (ACS) Nutrition and Physical Activity Cancer Prevention Guidelines is associated with reductions in overall cancer incidence and mortality, including site-specific cancers such as colorectal cancer. We examined the relationship between baseline adherence to the ACS guidelines and (1) baseline adenoma characteristics and (2) odds of recurrent colorectal adenomas over 3 years of follow-up. Cross-sectional and prospective analyses with a pooled sample of participants from the Wheat Bran Fiber (n = 503) and Ursodeoxycholic Acid (n = 854) trials were performed. A cumulative adherence score was constructed using baseline self-reported data regarding body size, diet, physical activity and alcohol consumption. Multivariable logistic regression demonstrated significantly reduced odds of having three or more adenomas at baseline for moderately adherent (odds ratio [OR] = 0.67, 95% confidence intervals [CI]: 0.46⁻0.99) and highly adherent (OR = 0.50, 95% CI: 0.31⁻0.81) participants compared to low adherers (p-trend = 0.005). Conversely, guideline adherence was not associated with development of recurrent colorectal adenoma (moderate adherence OR = 1.16, 95% CI: 0.85⁻1.59, high adherence OR = 1.23, 95% CI: 0.85⁻1.79)

Statistical Modeling of On-Site Wastewater Treatment System Life Cycle Performance and Risk

By 2050, it has been estimated that 70 percent of the world’s population will live in cities, concentrating waste as well as local environmental stresses. At the same time, decentralized approaches to sanitation are projected to grow due to the capital cost of sewers and centralized treatment facilities. Yet the common belief that technology will assure the performance of on-site systems over their life cycle may lead to significant underestimation of the actual risks to public and environmental health from owner-operated residential sanitation systems. Safe on-site storage, transformation and disposal of human waste require knowledge of how factors such as individual ownership, operations and management, and scale impact wastewater treatment reliability, risk and resilience under both normal and extreme conditions. This dissertation research is developed to fill a gap in performance-based knowledge of OWTS function, especially the likelihood of system failure over lifetime operation. As such, a data-based investigation of highly decentralized and privatized wastewater management represented by on-site wastewater treatment systems (OWTS) was conducted using data from OWTS located in Boulder County, Colorado. Data were acquired from County maintained repair permit application records, inspection documentation, and property attributes. Methods are developed to quantitatively diagnose components that determine OWTS life cycle performance such as reliability, risk, fragility, and resilience by applying commonly used statistical modeling approaches based on the Generalized Linear Model regression method. Statistical modeling is then applied to analyze two conditions not controlled by current OWTS design and siting regulations: owner behavior and weather-related hazards. Statistical model results confirm that owner-operations significantly affect life cycle OWTS functionality. Specifically, the results indicate the significant benefit of regulated inspections and maintenance as means to ensure that once installed, these systems continue to perform reliably and cost-effectively over their lifetime. Although a significant public information campaign (SepticSmart) has been maintained by the Boulder County Public Health Department, it is evident from the regression analysis that relying solely on public education about the importance of practices such as regular inspection and maintenance is insufficient to positively influence private owners’ decisions and prevent generation of externalities such as contaminant release from failed OWTS. A resilience framework is developed to demonstrate the degree to which decentralization influences systematic OWTS vulnerability to weather – both wetter-than-average conditions and extreme storm events, independent of individual OWTS operations. Widespread natural hazards such as flooding are found to affect the frequency and degree to which OWTS function is lost, and more importantly delay their recovery, attributable in part, to a demand surge for both materials and repair services when multiple systems fail simultaneously. Longer recoveries are likely to have environmental and public health consequences due to the prolonged release of contaminants as well as secondary costs related to homeowner losses resulting from a failed OWTS.Ultimately, the findings of this dissertation contribute to the decisions of planners, regulators and community stakeholders concerned with varying levels of wastewater treatment reliability, risk and resilience along the sanitation continuum from highly centralized and regulated collection and treatment infrastructure to relatively unregulated onsite systems operated by their owners. This research has demonstrated the importance of factors representing two heretofore unrecognized dimensions of OWTS life cycle performance – behavior of individual owners and enhanced vulnerability to natural hazards, and thus enables planners to decide if la

Regulation of chemokine receptor expression and function on CD4+T lymphocytes during central nervous system inflammation.

Chemokines are a family of cytokines that exhibit selective chemoattractant properties for target leukocytes, including CD4⁺ T lymphocytes, and play a significant role leukocyte migration. However, a target leukocyte can only respond to a chemokine if it expresses the cognate receptor(s). Recent studies have demonstrated alterations in both chemokine and chemokine receptor expression patterns in the CNS during experimental autoimmune encephalomyelitis (EAE), a model for Multiple Sclerosis. Accordingly, the aim of the research presented in this thesis was to investigate chemokine receptor regulation and function on CD4⁺ T lymphocytes during T cell-mediated central nervous system (CNS) inflammation in vivo. In the proteolipid protein (PLP)-induced model of EAE, two inflammatory (CXCR3 and CCR5) and one supposedly homeostatic (CXCR4) chemokine receptors were up regulated on CD4⁺ T cells during antigen-dependent clonal selection in the draining lymph nodes. As the CD4⁺ T cells migrated through the blood and into the CNS tissue, expression of these receptors remained elevated such that, at the peak of clinical disease, the majority of neuroantigen-specific CD4⁺ T cells in the CNS expressed elevated levels of CXCR4, CXCR3 and CCR5. Detailed characterisation of these receptors revealed that upregulation occurred in co-ordination with cellular division. Subsequent experiments were performed in order to determine the biological consequences of specific chemokine/receptor interactions during EAE. Amino terminal modifications of chemokines, which convert agonists to antagonists, have previously been shown to interfere with ligand/receptor interactions during inflammation. Therefore, a series of synthetic N-terminal chemokine mutants were initially tested in vitro for their ability to act as antagonists in preventing the migration of neuroantigen-activated lymphocytes to ligands of the receptors CXCR4, CXCR3 and CCR5. These analyses revealed that the synthetic mutants SDF-1 P2G, I-TAC 4-79 and RANTES 9-68 possessed potent antagonistic capacities. Following EAE induction, treatment every second day with the antagonists until day 15 resulted in a significant decrease in the severity of the neurological symptoms of EAE. Histological analyses demonstrated that the reduction in disease severity corresponded with a reduced number of inflammatory infiltrates in the spinal cords of antagonist-treated mice at peak clinical disease compared with control-treated mice. The ability to separate the disease process into two separate phases (sensitisation and effector) using adoptive transfer experiments provided a means to investigate the temporal and spatial control that specific chemokine/receptor interactions exerted during the pathogenesis of EAE. Accordingly, a series of ex vivo proliferation assays and adoptive transfer experiments were conducted. From these experiments, a potential role for the SDF-1/CXCR4 interaction was identified in the sensistisation phase of the disease. These results indicated that SDF-1/CXCL12 and CXCR4 interactions not only play a role in homeostasis, but may also provide costimulatory signals to antigen-stimulated CD4⁺ T cells. Converely, roles for I-TAC/CXCR3 and RANTES/CCR5 interactions, but not SDF-1/CXCR4 interactions were identified in the effector phase of EAE. Collectively, the results generated in the present thesis, together with those from other studies, enabled the construction of a model detailing the temporal and spatial parameters of chemokine/chemokine receptor regulation of CD4⁺ T cell activation and migration during a CD4⁺ T cell-mediated immune response in the CNS.Thesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science, 200

Earthquake Early Warning ShakeAlert System: Testing and Certification Platform

Earthquake early warning systems provide warnings to end users of incoming moderate to strong ground shaking from earthquakes. An earthquake early warning system, ShakeAlert, is providing alerts to beta end users in the western United States, specifically California, Oregon, and Washington. An essential aspect of the earthquake early warning system is the development of a framework to test modifications to code to ensure functionality and assess performance. In 2016, a Testing and Certification Platform (TCP) was included in the development of the Production Prototype version of ShakeAlert. The purpose of the TCP is to evaluate the robustness of candidate code that is proposed for deployment on ShakeAlert Production Prototype servers. TCP consists of two main components: a real‐time in situ test that replicates the real‐time production system and an offline playback system to replay test suites. The real‐time tests of system performance assess code optimization and stability. The offline tests comprise a stress test of candidate code to assess if the code is production ready. The test suite includes over 120 events including local, regional, and teleseismic historic earthquakes, recentering and calibration events, and other anomalous and potentially problematic signals. Two assessments of alert performance are conducted. First, point‐source assessments are undertaken to compare magnitude, epicentral location, and origin time with the Advanced National Seismic System Comprehensive Catalog, as well as to evaluate alert latency. Second, we describe assessment of the quality of ground‐motion predictions at end‐user sites by comparing predicted shaking intensities to ShakeMaps for historic events and implement a threshold‐based approach that assesses how often end users initiate the appropriate action, based on their ground‐shaking threshold. TCP has been developed to be a convenient streamlined procedure for objectively testing algorithms, and it has been designed with flexibility to accommodate significant changes in development of new or modified system code. It is expected that the TCP will continue to evolve along with the ShakeAlert system, and the framework we describe here provides one example of how earthquake early warning systems can be evaluated

Management of Swallowing Disorders: A Program for Professionals Working in Rural Areas

Research indicates that 74% of all nursing home patients experience eating difficulties sometime during their stay (Trupe, Siebens, & Siebens, 1984). Additionally, 59% of patients suffering from stroke experience some degree of dysphagia and aspiration difficulties (Echelard, Thoppil, & Melvin 1984). A significant number of the high risk dysphagia patients described above suffer from life threatening aspiration pneumonia. Consequently the management of swallowing disorders (Dysphagia) is of critical concern to hospital and nursing home personnel. Patients specficially at risk for dysphagia, according to recent studies, include those with head injury, stroke (CVA), and cerebral palsy. Also, patients experiencing cancer of the swallowing structures, diseases or disorders of the cranial nerves, and other neurological dysfuctions have been identified to be at increased risk. In rural areas, however, sophisticated diagnostic equipment that would facilitate dysphagia diagnosis is often unavailable. In addition, rural hospital and nursing home personnel (occupational therapists, physical therapists, speech pathologists and registered nurses) are often in a position to identify early signs of dysphagia but may not be trained in dysphagia identification or treatment. Consequently, it is imperative for these care providers to learn the screening skills necessary to identify dysphagia. When patients are identified as having, or being at an increased risk for, swallowing disorders are are treated accordingly, additional problems resulting from undiagnosed dysphagia may be prevented

Rapid Earthquake Characterization Using MEMS Accelerometers and Volunteer Hosts Following the M 7.2 Darfield, New Zealand, Earthquake

We test the feasibility of rapidly detecting and characterizing earthquakes with the Quake‐Catcher Network (QCN) that connects low‐cost microelectromechanical systems accelerometers to a network of volunteer‐owned, Internet‐connected computers. Following the 3 September 2010 M 7.2 Darfield, New Zealand, earthquake we installed over 180 QCN sensors in the Christchurch region to record the aftershock sequence. The sensors are monitored continuously by the host computer and send trigger reports to the central server. The central server correlates incoming triggers to detect when an earthquake has occurred. The location and magnitude are then rapidly estimated from a minimal set of received ground‐motion parameters. Full seismic time series are typically not retrieved for tens of minutes or even hours after an event. We benchmark the QCN real‐time detection performance against the GNS Science GeoNet earthquake catalog. Under normal network operations, QCN detects and characterizes earthquakes within 9.1 s of the earthquake rupture and determines the magnitude within 1 magnitude unit of that reported in the GNS catalog for 90% of the detections