Improving SPAWAR PEO C4I organizational alignment to better enable enterprise technical risk management

This thesis examined how the Navy's Program Executive Office Command, Control, Communications, Computers and Intelligence (PEO C4I) has performed enterprise risk management (ERM). Based on ERM literature, the study developed an analytical framework to assess PEO C4I's ERM practices against documented ERM best practices, including evaluating a new risk in terms of its impact on existing risks and ensuring risks are managed at the most detailed level possible. The thesis also utilized organizational alignment literature to include organizational alignment principles in the evaluation. Key principles include 1) every employee has the responsibility to manage risk and 2) multiple teams are able to manage a single risk. The resultant analytical framework was applied to PEO C4I and documented for application to other organizations. PEO C4I performed well in the areas of 1) evaluating risks in areas other than the originating program office and 2) providing the framework to elevate risks to leadership. PEO C4I could use improvement in cross-team risk coordination and development of enterprise models to provide context for enterprise risks. Recommended interventions focus on having more functional areas involved in risk mitigation and developing a common enterprise architecture to improve understanding of potential areas of risk.http://archive.org/details/improvingspawarp1094552965Civilian, Department of the NavyApproved for public release; distribution is unlimited

Chronic IL-1β-induced inflammation regulates epithelial-to-mesenchymal transition memory phenotypes via epigenetic modifications in non-small cell lung cancer.

Chronic inflammation facilitates tumor progression. We discovered that a subset of non-small cell lung cancer cells underwent a gradually progressing epithelial-to-mesenchymal (EMT) phenotype following a 21-day exposure to IL-1β, an abundant proinflammatory cytokine in the at-risk for lung cancer pulmonary and the lung tumor microenvironments. Pathway analysis of the gene expression profile and in vitro functional studies revealed that the EMT and EMT-associated phenotypes, including enhanced cell invasion, PD-L1 upregulation, and chemoresistance, were sustained in the absence of continuous IL-1β exposure. We referred to this phenomenon as EMT memory. Utilizing a doxycycline-controlled SLUG expression system, we found that high expression of the transcription factor SLUG was indispensable for the establishment of EMT memory. High SLUG expression in tumors of lung cancer patients was associated with poor survival. Chemical or genetic inhibition of SLUG upregulation prevented EMT following the acute IL-1β exposure but did not reverse EMT memory. Chromatin immunoprecipitation and methylation-specific PCR further revealed a SLUG-mediated temporal regulation of epigenetic modifications, including accumulation of H3K27, H3K9, and DNA methylation, in the CDH1 (E-cadherin) promoter following the chronic IL-1β exposure. Chemical inhibition of DNA methylation not only restored E-cadherin expression in EMT memory, but also primed cells for chemotherapy-induced apoptosis

Electronic Health Record Functionality Needed to Better Support Primary Care

Electronic health records (EHRs) must support primary care clinicians and patients, yet many clinicians remain dissatisfied with their system. This manuscript presents a consensus statement about gaps in current EHR functionality and needed enhancements to support primary care. The Institute of Medicine primary care attributes were used to define needs and Meaningful Use (MU) objectives to define EHR functionality. Current objectives remain disease- rather than whole-person focused, ignoring factors like personal risks, behaviors, family structure, and occupational and environmental influences. Primary care needs EHRs to move beyond documentation to interpreting and tracking information over time as well as patient partnering activities, support for team based care, population management tools that deliver care, and reduced documentation burden. While Stage 3 MU’s focus on outcomes is laudable, enhanced functionality is still needed including EHR modifications, expanded use of patient portals, seamless integration with external applications, and advancement of national infrastructure and policies

Author Correction: Chronic IL-1β-induced inflammation regulates epithelial-to-mesenchymal transition memory phenotypes via epigenetic modifications in non-small cell lung cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Improving SPAWAR PEO C4I organizational alignment to better enable enterprise technical risk management

This thesis examined how the Navy's Program Executive Office Command, Control, Communications, Computers and Intelligence (PEO C4I) has performed enterprise risk management (ERM). Based on ERM literature, the study developed an analytical framework to assess PEO C4I's ERM practices against documented ERM best practices, including evaluating a new risk in terms of its impact on existing risks and ensuring risks are managed at the most detailed level possible. The thesis also utilized organizational alignment literature to include organizational alignment principles in the evaluation. Key principles include 1) every employee has the responsibility to manage risk and 2) multiple teams are able to manage a single risk. The resultant analytical framework was applied to PEO C4I and documented for application to other organizations. PEO C4I performed well in the areas of 1) evaluating risks in areas other than the originating program office and 2) providing the framework to elevate risks to leadership. PEO C4I could use improvement in cross-team risk coordination and development of enterprise models to provide context for enterprise risks. Recommended interventions focus on having more functional areas involved in risk mitigation and developing a common enterprise architecture to improve understanding of potential areas of risk.http://archive.org/details/improvingspawarp1094552965Civilian, Department of the NavyApproved for public release; distribution is unlimited

Local Source Vp and Vs Tomography in the Mount St. Helens Region With the iMUSH Broadband Array

We present new 3-D P wave and S wave velocity models of the upper 20 km of the Mount St. Helens (MSH) region. These were obtained using local-source arrival time tomography from earthquakes and explosions recorded at 70 broadband stations deployed as part of the imaging Magma Under St. Helens (iMUSH) project and augmented by several data sets. Principal features of our models include (1) low P wave and S wave velocities along the St. Helens seismic zone to depths of at least 20 km corresponding to high conductivity imaged by iMUSH magnetotelluric studies. This delineates a zone of weakness that magma can exploit at the location of MSH; (2) a 5- to 7-km diameter, 6-15 km deep, 3-6% negative P wave and S wave velocity anomaly beneath MSH, consistent with previous estimates of the source region for recent eruptions. We interpret this as a magma storage region containing up to 15-20 km(3) of partial melt, which is about 5 times more than the largest documented eruption at MSH; (3) a broad region of low P wave velocity below 10-km depth extending between Mount Adams and Mount Rainier along and to the east of the main Cascade arc, which is likely due to high-temperature arc crust and possible presence of fluids or melt; (4) several anomalies associated with surface-mapped features, including high-velocity igneous units such as the Spud Mountain and Spirit Lake plutons and low velocities in the Chehalis sedimentary basin and the Indian Heaven volcanic field. Our results place further constraints on the geometry of these features at depth. Plain Language Summary We deployed 70 seismometers around Mount St. Helens volcano from 2014 to 2016, which measured the surface ground motion from hundreds of small earthquakes, as well as from 23 explosions that were set off in 2014. We recorded the onset time of shaking from these sources and used a specialized computer code to model how quickly seismic waves travel through the subsurface. Seismic wave speed can be influenced by several factors, including rock type, presence of magma/fluids, temperature, pressure, and how fractured the rock is. Based on the seismic wave speeds in our model, we make several geological interpretations, including (1) increased fluids or fractures, or presence of sedimentary rocks corresponding to elevated earthquake activity to the NNW of Mount St. Helens; (2) a magma storage region beneath the volcano similar to results from previous studies. Our model places further constraints on the orientation and size of the region; (3) a large zone of high temperatures and possible fluids or magma related to regional volcanism between and to the east of Mount Adams and Mount Rainier; (4) more detailed size and depth constraints on geological features seen at the surface, including sedimentary basins and rock units related to previous regional volcanism. Key Points New high-resolution P wave and S wave velocity models are calculated for the Mount St. Helens region Velocity models place further constraints on size and location of magma storage regions, seismic zones, sedimentary basins, and plutons These shed light on the accretionary history of the Siletzia terrane, with a transitional upper crustal boundary near Mount St. HelensNational Science Foundation of Sri Lanka6 month embargo; first published online 19 February 2020This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Internally Guided Lower Limb Movement Recruits Compensatory Cerebellar Activity in People With Parkinson's Disease

Background: Externally guided (EG) and internally guided (IG) movements are postulated to recruit two parallel neural circuits, in which motor cortical neurons interact with either the cerebellum or striatum via distinct thalamic nuclei. Research suggests EG movements rely more heavily on the cerebello-thalamo-cortical circuit, whereas IG movements rely more on the striato-pallido-thalamo-cortical circuit (1). Because Parkinson's (PD) involves striatal dysfunction, individuals with PD have difficulty generating IG movements (2).Objectives: Determine whether individuals with PD would employ a compensatory mechanism favoring the cerebellum over the striatum during IG lower limb movements.Methods: 22 older adults with mild-moderate PD, who had abstained at least 12 h from anti-PD medications, and 19 age-matched controls performed EG and IG rhythmic foot-tapping during functional magnetic resonance imaging. Participants with PD tapped with their right (more affected) foot. External guidance was paced by a researcher tapping participants' ipsilateral 3rd metacarpal in a pattern with 0.5 to 1 s intervals, while internal guidance was based on pre-scan training in the same pattern. BOLD activation was compared between tasks (EG vs. IG) and groups (PD vs. control).Results: Both groups recruited the putamen and cerebellar regions. The PD group demonstrated less activation in the striatum and motor cortex than controls. A task (EG vs. IG) by group (PD vs. control) interaction was observed in the cerebellum with increased activation for the IG condition in the PD group.Conclusions: These findings support the hypothesized compensatory shift in which the dysfunctional striatum is assisted by the less affected cerebellum to accomplish IG lower limb movement in individuals with mild-moderate PD. These findings are of relevance for temporal gait dysfunction and freezing of gait problems frequently noted in many people with PD and may have implications for future therapeutic application

Chronic IL-1β-induced inflammation regulates epithelial-to-mesenchymal transition memory phenotypes via epigenetic modifications in non-small cell lung cancer.

Chronic inflammation facilitates tumor progression. We discovered that a subset of non-small cell lung cancer cells underwent a gradually progressing epithelial-to-mesenchymal (EMT) phenotype following a 21-day exposure to IL-1β, an abundant proinflammatory cytokine in the at-risk for lung cancer pulmonary and the lung tumor microenvironments. Pathway analysis of the gene expression profile and in vitro functional studies revealed that the EMT and EMT-associated phenotypes, including enhanced cell invasion, PD-L1 upregulation, and chemoresistance, were sustained in the absence of continuous IL-1β exposure. We referred to this phenomenon as EMT memory. Utilizing a doxycycline-controlled SLUG expression system, we found that high expression of the transcription factor SLUG was indispensable for the establishment of EMT memory. High SLUG expression in tumors of lung cancer patients was associated with poor survival. Chemical or genetic inhibition of SLUG upregulation prevented EMT following the acute IL-1β exposure but did not reverse EMT memory. Chromatin immunoprecipitation and methylation-specific PCR further revealed a SLUG-mediated temporal regulation of epigenetic modifications, including accumulation of H3K27, H3K9, and DNA methylation, in the CDH1 (E-cadherin) promoter following the chronic IL-1β exposure. Chemical inhibition of DNA methylation not only restored E-cadherin expression in EMT memory, but also primed cells for chemotherapy-induced apoptosis

Author Correction: Chronic IL-1β-induced inflammation regulates epithelial-to-mesenchymal transition memory phenotypes via epigenetic modifications in non-small cell lung cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper