Bayesian comparison of cost-effectiveness of different clinical approaches to diagnose coronary artery disease

The objective of this study was to compare the cost-effectiveness of four clinical policies (policies I to IV) in the diagnosis of the presence or absence of coronary artery disease. A model based on Bayes' theorem and published clinical data was constructed to make these comparisons. Effectiveness was denned as either the number of patients with coronary disease diagnosed or as the number of quality-adjusted life years extended by therapy after the diagnosis of coronary disease.The following conclusions arise strictly from analysis of the model and may not necessarily be applicable to all situations. 1) As prevalence of coronary disease in the population increased, it caused a linear increase in cost per patient tested, but a hyperbolic decrease in cost per effect, that is, increased cost-effectiveness. Thus, cost-effectiveness of all policies (I to IV) was poor in populations with a prevalence of disease below 10%, for example, asymptomatic people with no risk factors. 2) Analysis of the model also indicates that at prevalences less than 80%, exercise thallium scintigraphy alone as a first test (policy II) is a more cost-effective initial test than is exercise electrocardiography alone as a first test (policy I) or exercise electrocardiography first combined with thallium imaging as a second test (policy IV). 3) Exercise electrocardiography before thallium imaging (policy IV) is more cost-effective than exercise electrocardiography alone (policy I) at prevalences less than 80%. 4) Noninvasive exercise testing before angiography (policies I, II and IV) is more cost-effective than using coronary angiography as the first and only test (policy III) at prevalences less than 80%. 5) Above a threshold value of prevalence of 80% (for example patients with typical angina), proceeding to angiography as the first test (policy III) was more cost-effective than initial noninvasive exercise tests (policies I, II and IV).One advantage of this quantitative model is that it estimates a threshold value of prevalence (80%) at which the rank order of policies changes. The model also allows substitution of different values for any variable as a way of accounting for the uncertainty inherent in the data. In conclusion, it is essential to consider the prevalence of disease when selecting the most cost-effective clinical approach to making a diagnosis

Editor\u27s Special Section-Larry Schnoor: A Celebration of His Impact on Intercollegiate Forensics

This panel is honoring Professor Larry Schnoor for his lifelong contribu-tions to Intercollegiate Forensics. National Individual Events Tournaments have continued to flourish under his direction. In addition, his constant mentoring has guaranteed the life of this activity. Panelists will describe Professor Schnoor‘s impact on the AFA-NIET, NFA, IOC and both his mentoring of forensic coaches and programs. Professor Schnoor will help to clarify and add to this oral history

Life and Operating Range Extension of the BPT-4000 Qualification Model Hall Thruster

Following completion of the 5,600 hr qualification life test of the BPT-4000 4.5 kW Hall Thruster Propulsion System, NASA and Aerojet have undertaken efforts to extend the qualified operating range and lifetime of the thruster to support a wider range of NASA missions. The system was originally designed for orbit raising and stationkeeping applications on military and commercial geostationary satellites. As such, it was designed to operate over a range of power levels from 3 to 4.5 kW. Studies of robotic exploration applications have shown that the cost savings provided by utilizing commercial technology that can operate over a wider range of power levels provides significant mission benefits. The testing reported on here shows that the 4.5 kW thruster as designed has the capability to operate efficiently down to power levels as low as 1 kW. At the time of writing, the BPT-4000 qualification thruster and cathode have accumulated over 400 hr of operation between 1 to 2 kW with an additional 600 hr currently planned. The thruster has demonstrated no issues with longer duration operation at low power

Method for the Destruction of Endotoxin in Synthetic Spider Silk Proteins

Although synthetic spider silk has impressive potential as a biomaterial, endotoxin contamination of the spider silk proteins is a concern, regardless of the production method. The purpose of this research was to establish a standardized method to either remove or destroy the endotoxins present in synthetic spider silk proteins, such that the endotoxin level was consistently equal to or less than 0.25 EU/mL, the FDA limit for similar implant materials. Although dry heat is generally the preferred method for endotoxin destruction, heating the silk proteins to the necessary temperatures led to compromised mechanical properties in the resultant materials. In light of this, other endotoxin destruction methods were investigated, including caustic rinses and autoclaving. It was found that autoclaving synthetic spider silk protein dopes three times in a row consistently decreased the endotoxin level 10–20 fold, achieving levels at or below the desired level of 0.25 EU/mL. Products made from triple autoclaved silk dopes maintained mechanical properties comparable to products from untreated dopes while still maintaining low endotoxin levels. Triple autoclaving is an effective and scalable method for preparing synthetic spider silk proteins with endotoxin levels sufficiently low for use as biomaterials without compromising the mechanical properties of the materials

A comparison of balloon injury models of endovascular lesions in rat arteries

BACKGROUND: Balloon injury (BI) of the rat carotid artery (CCA) is widely used to study intimal hyperplasia (IH) and decrease in lumen diameter (LD), but CCA's small diameter impedes the evaluation of endovascular therapies. Therefore, we validated BI in the aorta (AA) and iliac artery (CIA) to compare it with CCA. METHODS: Rats underwent BI or a sham procedure (control). Light microscopic evaluation was performed either directly or at 1, 2, 3, 4 and 16 weeks follow-up. The area of IH and the change in LD (LD at 16 weeks minus LD post BI) were compared. RESULTS: In the BI-groups the area of IH increased to 0.14 +/- 0.08 mm2 (CCA), 0.14 +/- 0.03 mm2 (CIA) and 0.12 +/- 0.04 mm2 (AA) at 16 weeks (NS). The LD decreased with 0.49 +/- 0.07 mm (CCA), compared to 0.22 +/- 0.07 mm (CIA) and 0.07 +/- 0.10 mm (AA) at 16 weeks (p < 0.05). The constrictive vascular remodelling (CVR = wall circumference loss combined with a decrease in LD) was -0.17 +/- 0.05 mm in CIA but absent in CCA and AA. No IH, no decrease in LD and no CVR was seen in the control groups. CONCLUSIONS: BI resulted in: (1.) a decrease in LD in CCA due to IH, (2.) a decrease in LD in CIA due to IH and CVR, (3.) no change in LD in AA, (4.) Comparable IH development in all arteries, (5.) CCA has no vasa vasorum compared to CIA and AA, (6.) The CIA model combines good access for 2 F endovascular catheters with a decrease in LD due to IH and CVR after BI

Combined TLR and CD40 Triggering Induces Potent CD8+ T Cell Expansion with Variable Dependence on Type I IFN

Toll-like receptors are important in the activation of innate immunity, and CD40 is a molecule critical for many T and B cell responses. Whereas agonists for either pathway have been used as vaccine adjuvants, we show that a combination of Toll-like receptor (TLR)7 and CD40 agonists synergize to stimulate CD8+ T cell responses 10–20-fold greater than the use of either agonist alone. Antigen-specific CD8+ T cells elicited from combination CD40/TLR7 treatment demonstrated both lytic activities and interferon (IFN)γ production and an enhanced secondary response to antigenic challenge. Agonists for TLRs 2/6, 3, 4, and 9 also synergized with CD40 stimulation, demonstrating that synergy with the CD40 pathway is a property of TLR-derived stimuli in general. The CD8+ T cell expansion induced by CD40/TLR7 triggering was independent of CD4+ T cells, IFNγ, and IL-12 but dependent on B7-mediated costimulation and surprisingly on type I IFN. These studies provide the rational basis for the use of TLR and CD40 agonists together as essential adjuvants to optimize vaccines designed to elicit protective or therapeutic immunity

Sacred Cows and Sympathetic Squirrels: The Importance of Biological Diversity to Human Health

Dobson and colleagues describe how some host species act to reduce the risk of transmission of virulent zoonotic pathogens to humans