Low thrust orbit determination program

Logical flow and guidelines are provided for the construction of a low thrust orbit determination computer program. The program, tentatively called FRACAS (filter response analysis for continuously accelerating spacecraft), is capable of generating a reference low thrust trajectory, performing a linear covariance analysis of guidance and navigation processes, and analyzing trajectory nonlinearities in Monte Carlo fashion. The choice of trajectory, guidance and navigation models has been made after extensive literature surveys and investigation of previous software. A key part of program design relied upon experience gained in developing and using Martin Marietta Aerospace programs: TOPSEP (Targeting/Optimization for Solar Electric Propulsion), GODSEP (Guidance and Orbit Determination for SEP) and SIMSEP (Simulation of SEP)

Anavip interaction with western pygmy rattlesnake venom: In vitro assessment of reactivity using SE-HPLC

Background: Every year there are a large number of venomous snake bites that occur around the world and especially in tropical areas. This is a problem that is faced worldwide with the World Health Organization classifying venomous snake bites as one of their highest priority neglected tropical diseases. One of the reasons for this classification is the short supply of antivenom compared to the number of snake envenomations that occurs each year. The standard of care for snake envenomation is administration of antivenom. Many antivenoms are polyvalent in that they are produced using venoms from multiple species of snakes. These polyvalent antivenoms can treat envenomation from the snake venoms that are used in the production, but also show cross-reactivity against snake venoms that share similar components. Determining the cross reactivities of antivenoms could help improve the quality of treatment, and provide a better understanding of venom-antivenom binding. Until recently there has only been one antivenom available for treatment of North American Crotaline envenomation. With the introduction of an F(ab')2 antivenom (Anavip) into the United States, we look at the cross-reactivity of the western pygmy rattlesnake, Sistrurus miliarius streckeri, against Anavip.Methods: SE-HPLC was used to assess cross-reactivity. SE-HPLC is a viable method to analyze antivenom-venom reactivity based on separation of higher molecular weight complexes that form vs unreacted components. Estimates of venom-antivenom reactivity was measured in reaction mixtures based on the increase in the elution profile area where higher molecular weight complexes are observed (region 1) and on the decrease in the elution profile area where reactants are observed (region 2). Reaction mixtures contained Anavip (1.0 mg/ml) and S. miliarius venom (0.125, 0.25, 0.5, or 1.0 mg/ml). Controls were Anavip and S. miliarius (1.0mg/ml). Mixtures were incubated at 37° C for 30 minutes, then stored at 4° C prior to SE-HPLC.Results: Cross-reactivity was seen between Anavip and S. miliarius venom based on changes in elution profile areas. A decrease in region 2 (reactants) and increase in region 1 (immune complexes) was observed at all venom-antivenom concentrations. The maximum venom-antivenom binding was calculated, based on changes in profile region areas, to be approximately 67% relative to the total area.Discussion/Conclusion: Apparent saturation of reactive antivenom was observed at all venom concentrations. Estimates of Anavip reactivity with S. miliarius venom are seen in the changes of the elution profile region areas, showing the formation of larger molecular weight complexes and decrease in reactants. This shows that Anavip could provide protective effects against S. miliarius envenomation. Further studies are needed to determine binding within a broader range of venom concentrations, as well as the composition of reactive and unreacted components. Results suggest that binding of Anavip to S.miliarius venom does occur, which is consistent with protective effects that are observed clinically

The Artificial Society Analytics Platform

Author's accepted manuscriptSocial simulation routinely involves the construction of artificial societies and agents within such societies. Currently there is insufficient discussion of best practices regarding the construction process. This chapter introduces the artificial society analytics platform (ASAP) as a way to spark discussion of best practices. ASAP is designed to be an extensible architecture capable of functioning as the core of many different types of inquiries into social dynamics. Here we describe ASAP, focusing on design decisions in several key areas, thereby exposing our assumptions and reasoning to critical scrutiny, hoping for discussion that can advance debate over best practices in artificial society construction. The five design decisions are related to agent characteristics, neighborhood interactions, evaluating agent credibility, agent marriage, and heritability of personality.acceptedVersio

Impact of varying degrees of renal dysfunction on transcatheter and surgical aortic valve replacement

BackgroundRenal impairment portends adverse outcomes in patients undergoing valvular heart surgery. The relationship between renal dysfunction in patients undergoing transcatheter aortic valve replacement (TAVR) is incompletely understood.MethodsA retrospective review of 1336 patients undergoing surgical aortic valve replacement (SAVR; 2002-2012) and 321 patients undergoing TAVR (2007-2012) was performed. Patients were divided into 3 glomerular filtration rate (GFR) groups: GFR greater than 60 mL/min, GFR 31 to 60 mL/min, and GFR 30 mL/min or less. Logistic and linear regression analysis was performed to estimate the TAVR effect on outcomes. Risk adjustments were made using the Society for Thoracic Surgeons (STS) predicted risk of mortality (PROM).ResultsTAVR patients were older (82 vs 65 years; P < .001), had a poorer ejection fraction (48% vs 53%; P < .001), were more likely female (45% vs 41%; P = .23), and had a higher STS PROM (11.9% vs 4.6%; P < .001). In-hospital mortality rates for TAVR and SAVR were 3.5% and 4.1%, respectively (P = .60), a result that marginally favors TAVR after risk adjustment (adjusted odds ratio = .52, P = .06). In SAVR patients, worsening preoperative renal failure was associated with increased in-hospital mortality (P = .004) and hospital (P < .001) and intensive care unit (ICU) (P < .001) lengths of stay. In contrast, worsening renal function did not influence in-hospital mortality (P = .78) and hospital (P < .23) and ICU (P = .88) lengths of stay in TAVR patients.ConclusionsWorsening renal function was associated with increased in-hospital mortality, hospital length of stay, and ICU length of stay in SAVR patients, but not in TAVR patients. This unexpected finding may have important clinical implications in patients with aortic stenosis and preoperative renal dysfunction

FAS-dependent cell death in α-synuclein transgenic oligodendrocyte models of multiple system atrophy

Multiple system atrophy is a parkinsonian neurodegenerative disorder. It is cytopathologically characterized by accumulation of the protein p25α in cell bodies of oligodendrocytes followed by accumulation of aggregated α-synuclein in so-called glial cytoplasmic inclusions. p25α is a stimulator of α-synuclein aggregation, and coexpression of α-synuclein and p25α in the oligodendroglial OLN-t40-AS cell line causes α-synuclein aggregate-dependent toxicity. In this study, we investigated whether the FAS system is involved in α-synuclein aggregate dependent degeneration in oligodendrocytes and may play a role in multiple system atrophy. Using rat oligodendroglial OLN-t40-AS cells we demonstrate that the cytotoxicity caused by coexpressing α-synuclein and p25α relies on stimulation of the death domain receptor FAS and caspase-8 activation. Using primary oligodendrocytes derived from PLP-α-synuclein transgenic mice we demonstrate that they exist in a sensitized state expressing pro-apoptotic FAS receptor, which makes them sensitive to FAS ligand-mediated apoptosis. Immunoblot analysis shows an increase in FAS in brain extracts from multiple system atrophy cases. Immunohistochemical analysis demonstrated enhanced FAS expression in multiple system atrophy brains notably in oligodendrocytes harboring the earliest stages of glial cytoplasmic inclusion formation. Oligodendroglial FAS expression is an early hallmark of oligodendroglial pathology in multiple system atrophy that mechanistically may be coupled to α-synuclein dependent degeneration and thus represent a potential target for protective intervention

Evaluated Community Fire Safety Interventions in the United States: A Review of Current Literature

The purpose of the study was to assess the state of fire prevention research, provide an updated synthesis of evaluated fire prevention programs, and discuss the role of fire fighters and data systems in prevention efforts. The review included all evaluations of U.S. based fire prevention interventions published between January 1998 and September 2004 and any earlier articles about U.S. fire prevention interventions not included in two prior review articles. We retrieved information from each identified study including evaluation findings, involvement of fire service personnel and use of existing data systems. We identified twelve articles: seven reported on smoke alarm interventions, three on multi-faceted programs, and two other programs. Five programs involved fire service personnel in the design, implementation, and/or evaluation, and three used existing data systems. Studies reviewed suggest that canvassing and smoke alarm installations are the most effective means of distributing alarms and increasing the functional status of distributed alarms. The functionality of smoke alarms, an issue noted in earlier reviews, remains a problem. Programs involving partnerships with fire departments have indicated success in preventing fires and deaths, improving smoke alarm ownership and functional status, and improving children’s fire safety knowledge. Using existing data systems to target and to evaluate interventions was effective. In the years since prior reviews, some improvements in the rigor of evaluation designs have been made, but there is still a need for high quality evaluations that will inform fire injury prevention efforts

G2019S mutation in the leucine-rich repeat kinase 2 gene is not associated with multiple system atrophy

Multiple system atrophy (MSA) is characterized clinically by Parkinsonism, cerebellar dysfunction, and autonomic impairment. Multiple mutations in the LRRK2 gene are associated with parkinsonian disorders, and the most common one, the G2019S mutation, has been found in ∼1% of sporadic cases of Parkinsonism. In a well-characterized cohort of 136 subjects with probable MSA and 110 neurologically evaluated control subjects, none carried the G2019S mutation. We conclude that the G2019S mutation in the LRRK2 gene is unlikely to be associated with MSA. © 2007 Movement Disorder SocietyPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56014/1/21343_ftp.pd

Combined epicardial and endocardial ablation for atrial fibrillation:Best practices and guide to hybrid convergent procedures

The absence of strategies to consistently and effectively address nonparoxysmal atrial fibrillation by nonpharmacological interventions has represented a long-standing treatment gap. A combined epicardial/endocardial ablation strategy, the hybrid Convergent procedure, was developed in response to this clinical need. A subxiphoid incision is used to access the pericardial space facilitating an epicardial ablation directed at isolation of the posterior wall of the left atrium. This is followed by an endocardial ablation to complete isolation of the pulmonary veins and for additional ablation as needed. Experience gained with the hybrid Convergent procedure during the last decade has led to the development and adoption of strategies to optimize the technique and mitigate risks. Additionally, a surgical and electrophysiology "team" approach including comprehensive training is believed critical to successfully develop the hybrid Convergent program. A recently completed randomized clinical trial indicated that this ablation strategy is superior to an endocardial-only approach for patients with persistent atrial fibrillation. In this review, we propose and describe best practice guidelines for hybrid Convergent ablation on the basis of a combination of published data, author consensus, and expert opinion. A summary of clinical outcomes, emerging evidence, and future perspectives is also given