Some studies of expansion rings in rocket motors

This thesis document was issued under the authority of another institution, not NPS. At the time it was written, a copy was added to the NPS Library collection for reasons not now known. It has been included in the digital archive for its historical value to NPS. Not believed to be a CIVINS (Civilian Institutions) title.http://www.archive.org/details/somestudiesofexp00kleiU.S. Navy (U.S.N.) authors

Economic Evaluation of Fungal Meningitis Outbreak Response in New River Valley: Local Health Department Perspective

Background: The multi-state fungal meningitis outbreak started in September 2012 in Tennessee. The cause of the outbreak was injection of contaminated lots of methylprednisolone acetate used in epidural spinal injections. Roanoke and New River Valley were the epicenter of this outbreak in Virginia, with two clinical centers having administered the contaminated injections to their patients. New River Health District, in coordination with hospitals, and state and federal agencies, deployed its resources to control the local impact of the outbreak. Purpose: The objective of this study was to conduct an economic evaluation of the fungal meningitis outbreak response in New River Valley of Virginia, from the local public health department perspective. Methods: The health department conducted the outbreak investigation from October 2012 until March 2013 to ascertain that all possible cases were identified and treated. Data were collected on the costs associated with the local health department in the outbreak response, and the epidemiologic effectiveness estimated, using the metric of disability adjusted life years (DALYs). Results: The cost incurred by the local health department was estimated to be $30,493; the epidemiologic effectiveness was estimated to be 138 DALYs averted among the patients, for an incremental cost-effectiveness ratio of$221 per DALY averted. Implications: The incremental cost effectiveness ratio of the fungal meningitis outbreak response in New River Valley assists the local health department to analyze the costs and epidemiologic effectiveness of the outbreak response

Epidemiological Effectiveness and Cost of a Fungal Meningitis Outbreak Response in New River Valley, Virginia: Local Health Department and Clinical Perspectives.

OBJECTIVE: We evaluated the effectiveness and cost of a fungal meningitis outbreak response in the New River Valley of Virginia during 2012-2013 from the perspective of the local public health department and clinical facilities. The fungal meningitis outbreak affected 23 states in the United States with 751 cases and 64 deaths in 20 states; there were 56 cases and 5 deaths in Virginia. METHODS: We conducted a partial economic evaluation of the fungal meningitis outbreak response in New River Valley. We collected costs associated with the local health department and clinical facilities in the outbreak response and estimated the epidemiological effectiveness by using disability-adjusted life years (DALYs) averted. RESULTS: We estimated the epidemiological effectiveness of this outbreak response to be 153 DALYs averted among the patients, and the costs incurred by the local health department and clinical facilities to be $30,413 and$39,580, respectively. CONCLUSIONS: We estimated the incremental cost-effectiveness ratio of $198 per DALY averted and$258 per DALY averted from the local health department and clinical perspectives, respectively, thereby assisting in impact evaluation of the outbreak response by the local health department and clinical facilities. (Disaster Med Public Health Preparedness. 2018;12:38-46)

Clinical Response, Outbreak Investigation, and Epidemiology of the Fungal Meningitis Epidemic in the United States: Systematic Review.

We conducted a systematic review of the 2012-2013 multistate fungal meningitis epidemic in the United States from the perspectives of clinical response, outbreak investigation, and epidemiology. Articles focused on clinical response, outbreak investigation, and epidemiology were included, whereas articles focused on compounding pharmacies, legislation and litigation, diagnostics, microbiology, and pathogenesis were excluded. We reviewed 19 articles by use of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework. The source of the fungal meningitis outbreak was traced to the New England Compounding Center in Massachusetts, where injectable methylprednisolone acetate products were contaminated with the predominant pathogen, Exserohilum rostratum. As of October 23, 2013, the final case count stood at 751 patients and 64 deaths, and no additional cases are anticipated. The multisectoral public health response to the fungal meningitis epidemic from the hospitals, clinics, pharmacies, and the public health system at the local, state, and federal levels led to an efficient epidemiological investigation to trace the outbreak source and rapid implementation of multiple response plans. This systematic review reaffirms the effective execution of a multisectoral public health response and efficient delivery of the core functions of public health assessment, policy development, and service assurances to improve population health

Motion-corrected model-based reconstruction for 2D myocardial T1 mapping

PURPOSE: To allow for T1 mapping of the myocardium within 2.3 s for a 2D slice utilizing cardiac motion-corrected, model-based image reconstruction. METHODS: Golden radial data acquisition is continuously carried out for 2.3 s after an inversion pulse. In a first step, dynamic images are reconstructed which show both contrast changes due to T1 recovery and anatomical changes due to the heartbeat. An image registration algorithm with a signal model for T1 recovery is applied to estimate non-rigid cardiac motion. In a second step, estimated motion fields are applied during an iterative model-based T1 reconstruction. The approach was evaluated in numerical simulations, phantom experiments and in in-vivo scans in healthy volunteers. RESULTS: The accuracy of cardiac motion estimation was shown in numerical simulations with an average motion field error of 0.7 ± 0.6 mm for a motion amplitude of 5.1 mm. The accuracy of T1 estimation was demonstrated in phantom experiments, with no significant difference (p = 0.13) in T1 estimated by the proposed approach compared to an inversion-recovery reference method. In vivo, the proposed approach yielded 1.3 × 1.3 mm T1 maps with no significant difference (p = 0.77) in T1 and SDs in comparison to a cardiac-gated approach requiring 16 s scan time (i.e., seven times longer than the proposed approach). Cardiac motion correction improved the precision of T1 maps, shown by a 40% reduced SD. CONCLUSION: We have presented an approach that provides T1 maps of the myocardium in 2.3 s by utilizing both cardiac motion correction and model-based T1 reconstruction

Economic Evaluation of Fungal Meningitis Outbreak Response in New River Valley: Local Health Department Perspective.

BACKGROUND: The multi-state fungal meningitis outbreak started in September 2012 in Tennessee. The cause of the outbreak was injection of contaminated lots of methylprednisolone acetate used in epidural spinal injections. Roanoke and New River Valley were the epicenter of this outbreak in Virginia, with two clinical centers having administered the contaminated injections to their patients. New River Health District, in coordination with hospitals, and state and federal agencies, deployed its resources to control the local impact of the outbreak. PURPOSE: The objective of this study was to conduct an economic evaluation of the fungal meningitis outbreak response in New River Valley of Virginia, from the local public health department perspective. METHODS: The health department conducted the outbreak investigation from October 2012 until March 2013 to ascertain that all possible cases were identified and treated. Data were collected on the costs associated with the local health department in the outbreak response, and the epidemiologic effectiveness estimated, using the metric of disability adjusted life years (DALYs). RESULTS: The cost incurred by the local health department was estimated to be $30,493; the epidemiologic effectiveness was estimated to be 138 DALYs averted among the patients, for an incremental cost-effectiveness ratio of$221 per DALY averted. IMPLICATIONS: The incremental cost effectiveness ratio of the fungal meningitis outbreak response in New River Valley assists the local health department to analyze the costs and epidemiologic effectiveness of the outbreak response

3D model-based super-resolution motion-corrected cardiac T1 mapping

OBJECTIVE: To provide 3D high-resolution cardiac T1 maps using model-based super-resolution reconstruction (SRR). APPROACH: Due to signal-to-noise ratio (SNR) limitations and the motion of the heart during imaging, often 2D T1 maps with only low through-plane resolution (i.e. slice thickness of 6 to 8 mm) can be obtained. Here, a model-based SRR approach is presented, which combines multiple stacks of 2D acquisitions with 6 to 8 mm slice thickness and generates 3D high-resolution T1 maps with a slice thickness of 1.5 to 2 mm. Every stack was acquired in a different breath hold (BH) and any misalignment between BH was corrected retrospectively. The novelty of the proposed approach is the BH correction and the application of model-based SRR on cardiac T1 Mapping. The proposed approach was evaluated in numerical simulations and phantom experiments and demonstrated in four healthy subjects. MAIN RESULTS: Alignment of BH states was essential for SRR even in healthy volunteers. In simulations, respiratory motion could be estimated with an RMS error of 0.18 ± 0.28 mm. SRR improved the visualization of small structures. High accuracy and precision (average standard deviation of 69.62 ms) of the T1 values was ensured by SRR while the detectability of small structures increased by 40%. SIGNIFICANCE: The proposed SRR approach provided T1 maps with high in-plane and high through-plane resolution (1.3×1.3×1.5 to 2 mm(3)). The approach led to improvements in the visualization of small structures and precise T1 values

iPSC-derived reactive astrocytes from patients with multiple-sclerosis protect cocultured neurons in inflammatory conditions

Multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system (CNS). The individual course is highly variable with complete remission in some patients and relentless courses in others. We generated induced pluripotent stem cells (iPSCs) to investigate possible mechanisms in benign MS (BMS), compared to progressive MS (PMS). We differentiated neurons and astrocytes that were then stressed with inflammatory cytokines typically associated with MS. TNFα/IL-17A treatment increased neurite damage in MS neurons irrespective of clinical phenotypes. In contrast, TNFα/IL-17A-reactive BMS astrocytes cultured with healthy control (HC) neurons exhibited significantly decreased axonal damage, compared to PMS astrocytes. Accordingly, single cell transcriptomic analysis of BMS-astrocyte co-cultured neurons demonstrated upregulated pathways of neuronal resilience, namely these astrocytes revealed differential growth factor expression. Moreover, supernatants from BMS astrocyte-neuron co-cultures rescued TNFα/IL-17-induced neurite damage. This process was associated with the unique expression of the growth factors, LIF and TGF-β1, as induced by TNFα/IL-17 and JAK-STAT activation. Our findings highlight a potential therapeutic role of modulating astrocyte phenotypes that generate a neuroprotective milieu preventing permanent neuronal damage

HIF prolyl hydroxylase 2/3 deletion disrupts astrocytic integrity and exacerbates neuroinflammation

Astrocytes constitute the parenchymal border of the blood-brain barrier (BBB), modulate the exchange of soluble and cellular elements, and are essential for neuronal metabolic support. Thus, astrocytes critically influence neuronal network integrity. In hypoxia, astrocytes upregulate a transcriptional program that has been shown to boost neuroprotection in several models of neurological diseases. We investigated transgenic mice with astrocyte-specific activation of the hypoxia-response program by deleting the oxygen sensors, HIF prolyl-hydroxylase domains 2 and 3 (Phd2/3). We induced astrocytic Phd2/3 deletion after onset of clinical signs in experimental autoimmune encephalomyelitis (EAE) that led to an exacerbation of the disease mediated by massive immune cell infiltration. We found that Phd2/3-ko astrocytes, though expressing a neuroprotective signature, exhibited a gradual loss of gap-junctional Connexin-43 (Cx43), which was induced by vascular endothelial growth factor-alpha (Vegf-a) expression. These results provide mechanistic insights into astrocyte biology, their critical role in hypoxic states, and in chronic inflammatory CNS diseases