Synthesis, Interdiction, and Protection of Layered Networks

This research developed the foundation, theory, and framework for a set of analysis techniques to assist decision makers in analyzing questions regarding the synthesis, interdiction, and protection of infrastructure networks. This includes extension of traditional network interdiction to directly model nodal interdiction; new techniques to identify potential targets in social networks based on extensions of shortest path network interdiction; extension of traditional network interdiction to include layered network formulations; and develops models/techniques to design robust layered networks while considering trade-offs with cost. These approaches identify the maximum protection/disruption possible across layered networks with limited resources, find the most robust layered network design possible given the budget limitations while ensuring that the demands are met, include traditional social network analysis, and incorporate new techniques to model the interdiction of nodes and edges throughout the formulations. In addition, the importance and effects of multiple optimal solutions for these (and similar) models is investigated. All the models developed are demonstrated on notional examples and were tested on a range of sample problem sets

An Analysis of Multiple Layered Networks

Current infrastructure network models of single functionality do not typically account for the interdependent nature of infrastructure networks. Infrastructure networks are generally modeled individually, as an isolated network or with minimal recognition of interactions. This research develops a methodology to model the individual infrastructure network types while explicitly modeling their interconnected effects. The result is a formulation built with two sets of variables (the original set to model infrastructure characteristics and an additional set representing cuts of interdependent elements). This formulation is decomposed by variable type using Benders Partitioning and solved to optimality using a Benders Partitioning algorithm. Current infrastructure network models of single functionality do not typically account for the interdependent nature of infrastructure networks, Infrastructure networks are generally modeled individually, as an isolated network or with minimal recognition of interactions, This research develops a methodology to model the individual infrastructure network types while explicitly modeling their interconnected effects, The result is a formulation built with two sets of variables (the original set to model infrastructure characteristics and an additional set representing cuts of interdependent elements) This formulation is decomposed by variable type using Benders\u27 Partitioning and solved to optimality using a Benders\u27 Partitioning algorithm

Tracking ground state Ba+ ions in an expanding laser–plasma plume using time-resolved vacuum ultraviolet photoionization imaging

We report results from a study of the integrated column density and expansion dynamics of ground-state-selected Ba+ ions in a laser–plasma plume using a new experimental system—VPIF (vacuum-ultraviolet photoabsorption imaging facility). The ions are tracked by recording the attenuation of a pulsed and collimated vacuum ultraviolet beam, tuned to the 5p–6d inner-shell resonance of singly ionized barium, as the expanding plasma plume moves across it. The attenuated beam is allowed to fall on a CCD array where the spatial distribution of the absorption is recorded. Time-resolved ion velocity and integrated column density maps are readily extracted from the photoionization images

Infrared colours and inferred masses of metal-poor giant stars in the Keplerfield

Intrinsically luminous giant stars in the Milky Way are the only potential volume-complete tracers of the distant disk, bulge, and halo. The chemical abundances of metal-poor giants also reflect the compositions of the earliest star-forming regions, providing the initial conditions for the chemical evolution of the Galaxy. However, the intrinsic rarity of metal-poor giants combined with the difficulty of efficiently identifying them with broad-band optical photometry has made it difficult to exploit them for studies of the Milky Way. One long-standing problem is that photometric selections for giant and/or metal-poor stars frequently include a large fraction of metal-rich dwarf contaminants. We re-derive a giant star photometric selection using existing public g-band and narrow-band DDO51photometry obtained in the Keplerfield. Our selection is simple and yields a contamination rate of main-sequence stars of ≲1% and a completeness of about 80 % for giant stars with Teff ≲ 5250 K - subject to the selection function of the spectroscopic surveys used to estimate these rates, and the magnitude range considered (11 ≲ g ≲ 15). While the DDO51filter is known to be sensitive to stellar surface gravity, we further show that the mid-infrared colours of DDO51-selected giants are strongly correlated with spectroscopic metallicity. This extends the infrared metal-poor selection developed by Schlaufman & Casey, demonstrating that the principal contaminants in their selection can be efficiently removed by the photometric separation of dwarfs and giants. This implies that any similarly efficient dwarf/giant discriminant (e.g., Gaiaparallaxes) can be used in conjunction with WISEcolours to select samples of giant stars with high completeness and low contamination. We employ our photometric selection to identify three metal-poor giant candidates in the Keplerfield with global asteroseismic parameters and find that masses inferred for these three stars using standard asteroseismic scaling relations are systematically over-estimated by 20-175%. Taken at face value, this small sample size implies that standard asteroseismic scaling relations over-predict stellar masses for metal-poor giant stars

Reduction of leukocyte microvascular adherence and preservation of blood-brain barrier function by superoxide-lowering therapies in a piglet model of neonatal asphyxia

Background: Asphyxia is the most common cause of brain damage in newborns. Substantial evidence indicates that leukocyte recruitment in the cerebral vasculature during asphyxia contributes to this damage. We tested the hypothesis that superoxide radical (O2⋅_) promotes an acute post-asphyxial inflammatory response and blood-brain barrier (BBB) breakdown. We investigated the effects of removing O2⋅_ by superoxide dismutase (SOD) or C3, the cell-permeable SOD mimetic, in protecting against asphyxia-related leukocyte recruitment. We also tested the hypothesis that xanthine oxidase activity is one source of this radical.Methods: Anesthetized piglets were tracheostomized, ventilated, and equipped with closed cranial windows for the assessment of post-asphyxial rhodamine 6G-labeled leukocyte-endothelial adherence and microvascular permeability to sodium fluorescein in cortical venules. Asphyxia was induced by discontinuing ventilation. SOD and C3 were administered by cortical superfusion. The xanthine oxidase inhibitor oxypurinol was administered intravenously.Results: Leukocyte-venular adherence significantly increased during the initial 2 h of post-asphyxial reperfusion. BBB permeability was also elevated relative to non-asphyxial controls. Inhibition of O2⋅_ production by oxypurinol, or elimination of O2⋅_ by SOD or C3, significantly reduced rhodamine 6G-labeled leukocyte-endothelial adherence and improved BBB integrity, as measured by sodium fluorescein leak from cerebral microvessels.Conclusion: Using three different strategies to either prevent formation or enhance elimination of O2⋅_ during the post-asphyxial period, we saw both reduced leukocyte adherence and preserved BBB function with treatment. These findings suggest that agents which lower O2⋅_ in brain may be attractive new therapeutic interventions for the protection of the neonatal brain following asphyxia

Risk Factors for Major Early Adverse Events Related to Cardiac Catheterization in Children and Young Adults With Pulmonary Hypertension: An Analysis of Data From the IMPACT (Improving Adult and Congenital Treatment) Registry.

BACKGROUND: Cardiac catheterization is the gold standard for assessment and follow-up of patients with pulmonary hypertension (PH). To date, there are limited data about the factors that influence the risk of catastrophic adverse events after catheterization in this population. METHODS AND RESULTS: A retrospective multicenter cohort study was performed to measure risk of catastrophic adverse outcomes after catheterization in children and young adults with PH and identify risk factors for these outcomes. All catheterizations in children and young adults, aged 0 to 21 years, with PH at hospitals submitting data to the IMPACT (Improving Adult and Congenital Treatment) registry between January 1, 2011, and December 31, 2015, were studied. Using mixed-effects multivariable regression, we assessed the association between prespecified subject-, procedure-, and center-level covariates and the risk of death, cardiac arrest, or mechanical circulatory support during or after cardiac catheterization. A total of 8111 procedures performed in 7729 subjects at 77 centers were studied. The observed risk of the composite outcome was 1.4%, and the risk of death before discharge was 5.2%. Catheterization in prematurely born neonates and nonpremature infants was associated with increased risk of catastrophic adverse event, as was precatheterization treatment with inotropes and lower systemic arterial saturation. Secondary analyses demonstrated the following: (1) increasing volumes of catheterization in patients with PH were associated with reduced risk of composite outcome (odds ratio, 0.8 per 10 procedures; CONCLUSIONS: Young patients with PH are a high-risk population for diagnostic and interventional cardiac catheterization. Hospital experience with PH is associated with reduced risk, independent of total catheterization case volume

Improving Outcomes for Infants with Single Ventricle Physiology through Standardized Feeding during the Interstage

Congenital heart disease is identified as the most common birth defect with single ventricle physiology carrying the highest mortality. Staged surgical palliation is required for treatment, with mortality historically as high as 22% in the four- to six-month period from the first- to second-stage surgical palliation, known as the interstage. A standardized postoperative feeding approach was implemented through an evidence-based protocol, parent engagement, and interprofessional team rounds. Five infants with single ventricle physiology preprotocol were compared with five infants who received the standardized feeding approach. Mann- Whitney tests were conducted to evaluate the hypotheses that infants in the intervention condition would consume more calories and have a positive change inweight-to-age -score (WAZ) and shorter length of stay (LOS) following the first and second surgeries compared to infants in the control condition. After the protocol, the change inWAZ during the interstage increased by virtually one standard deviation from 0.05 to 0.91.Median LOS dropped 32% after the first surgery and 43% after the second surgery. Since firstand second-stage palliative surgeries occur within the same year of life, this represents savings of $500,000 to$800,000 per year in a 10-infant model.The standardized feeding approach improved growth in single ventricle infants while concurrently lowering hospital costs

Reach and adoption of a Geriatric Emergency Department Accreditation program in the United States

STUDY OBJECTIVE: The objectives of this study were to describe the reach and adoption of Geriatric Emergency Department Accreditation (GEDA) program and care processes instituted at accredited geriatric emergency departments (EDs). METHODS: We analyzed a cross-section of a cohort of US EDs that received GEDA from May 2018 to March 2021. We obtained data from the American College of Emergency Physicians and publicly available sources. Data included GEDA level, geographic location, urban/rural designation, and care processes instituted. Frequencies and proportions and median and interquartile ranges were used to summarize categorical and continuous data, respectively. RESULTS: Over the study period, 225 US geriatric ED accreditations were issued and included in our analysis-14 Level 1, 21 Level 2, and 190 Level 3 geriatric EDs; 5 geriatric EDs reapplied and received higher-level accreditation after initial accreditation at a lower level. Only 9 geriatric EDs were in rural regions. There was significant heterogeneity in protocols enacted at geriatric EDs; minimizing urinary catheter use and fall prevention were the most common. CONCLUSION: There has been rapid growth in geriatric EDs, driven by Level 3 accreditation. Most geriatric EDs are in urban areas, indicating the potential need for expansion beyond these areas. Future research evaluating the impact of GEDA on health care utilization and patient-oriented outcomes is needed

Renal safety of zoledronic acid with thalidomide in patients with myeloma: a pharmacokinetic and safety sub-study

BACKGROUND: Cases of impaired renal function have been reported in patients who had been treated with both zoledronic acid and thalidomide for myeloma. Hence, we conducted a safety study of zoledronic acid and thalidomide in myeloma patients participating in a trial of maintenance therapy. METHODS: Twenty-four patients who were enrolled in a large randomized trial of thalidomide vs no thalidomide maintenance therapy for myeloma, in which all patients also received zoledronic acid, were recruited to a pharmacokinetic and renal safety sub-study, and followed for up to 16 months. RESULTS: No significant differences by Wilcoxon rank-sum statistic were found in zoledronic acid pharmacokinetics or renal safety for up to 16 months in patients randomized to thalidomide or not. CONCLUSION: In myeloma patients receiving maintenance therapy, the combination of zoledronic acid and thalidomide appears to confer no additional renal safety risks over zoledronic acid alone

Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell–mediated liver damage

Hepatitis B virus (HBV) causes chronic infection in more than 350 million people worldwide. It replicates in hepatocytes but is non-cytopathic; liver damage is thought to be immune mediated. Here, we investigated the role of innate immune responses in mediating liver damage in patients with chronic HBV infection. Longitudinal analysis revealed a temporal correlation between flares of liver inflammation and fluctuations in interleukin (IL)-8, interferon (IFN)-α, and natural killer (NK) cell expression of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) directly ex vivo. A cross-sectional study confirmed these findings in patients with HBV-related liver inflammation compared with healthy carriers. Activated, TRAIL-expressing NK cells were further enriched in the liver of patients with chronic HBV infection, while their hepatocytes expressed increased levels of a TRAIL death–inducing receptor. IFN-α concentrations found in patients were capable of activating NK cells to induce TRAIL-mediated hepatocyte apoptosis in vitro. The pathogenic potential of this pathway could be further enhanced by the ability of the IFN-α/IL-8 combination to dysregulate the balance of death-inducing and regulatory TRAIL receptors expressed on hepatocytes. We conclude that NK cells may contribute to liver inflammation by TRAIL-mediated death of hepatocytes and demonstrate that this non-antigen–specific mechanism can be switched on by cytokines produced during active HBV infection