Mechanistic mathematical models: An underused platform for HPV research

Health economic modeling has become an invaluable methodology for the design and evaluation of clinical and public health interventions against the human papillomavirus (HPV) and associated diseases. At the same time, relatively little attention has been paid to a different yet complementary class of models, namely that of mechanistic mathematical models. The primary focus of mechanistic mathematical models is to better understand the intricate biologic mechanisms and dynamics of disease. Inspired by a long and successful history of mechanistic modeling in other biomedical fields, we highlight several areas of HPV research where mechanistic models have the potential to advance the field. We argue that by building quantitative bridges between biologic mechanism and population level data, mechanistic mathematical models provide a unique platform to enable collaborations between experimentalists who collect data at different physical scales of the HPV infection process. Through such collaborations, mechanistic mathematical models can accelerate and enhance the investigation of HPV and related diseases

Buckling Testing and Analysis of Honeycomb Sandwich Panel Arc Segments of a Full-Scale Fairing Barrel Part 4: Six-ply Out-of-Autoclave Facesheets

Four honeycomb sandwich panel types, representing 1/16th arc segments of a 10-m diameter barrel section of the Heavy Lift Launch Vehicle (HLLV), were manufactured and tested under the NASA Composites for Exploration program and the NASA Constellation Ares V program. Two configurations were chosen for the panels: 6-ply facesheets with 1.125 in. honeycomb core and 8-ply facesheets with 1.000 in. honeycomb core. Additionally, two separate carbon fiber/epoxy material systems were chosen for the facesheets: in-autoclave IM7/977-3 and out-of-autoclave T40-800b/5320-1. Smaller 3 ft. by 5 ft. panels were cut from the 1/16th barrel sections. These panels were tested under compressive loading at the NASA Langley Research Center (LaRC). Furthermore, linear eigenvalue and geometrically nonlinear finite element analyses were performed to predict the compressive response of each 3 ft. by 5 ft. panel. This manuscript summarizes the experimental and analytical modeling efforts pertaining to the panels composed of 6-ply, T40-800b/5320-1 facesheets (referred to as Panels D). To improve the robustness of the geometrically nonlinear finite element model, measured surface imperfections were included in the geometry of the model. Both the linear and nonlinear models yield good qualitative and quantitative predictions. Additionally, it was correctly predicted that the panel would fail in buckling prior to failing in strength. Furthermore, three-dimensional (3D) effects on the compressive response of the panel were studied

Accurate measurement of the time delay in the response of the LIGO gravitational wave detectors

We present a method to precisely calibrate the time delay in a long baseline gravitational-wave interferometer. An accurate time stamp is crucial for data analysis of gravitational wave detectors, especially when performing coincidence and correlation analyses between multiple detectors. Our method uses an intensity-modulated radiation pressure force to actuate on the mirrors. The time delay is measured by comparing the phase of the signal at the actuation point with the phase of the recorded signal within the calibrated data stream used for gravitational wave searches. Because the signal-injection path is independent of the interferometer's control system, which is used for the standard calibration, this method can be an independent verification of the timing error in the system. A measurement performed with the 4 km interferometer at the LIGO Hanford Observatory shows a 1 µs relative accuracy when averaging over 50 min. Our understanding of the systematic time delay in the detector response has reached the level of 10 µs

Adding a quadrivalent human papillomavirus vaccine to the UK cervical cancer screening programme: A cost-effectiveness analysis

<p>Abstract</p> <p>Background</p> <p>We assessed the cost-effectiveness of adding a quadrivalent (6/11/16/18) human papillomavirus (HPV) vaccine to the current screening programme in the UK compared to screening alone.</p> <p>Methods</p> <p>A Markov model of the natural history of HPV infection incorporating screening and vaccination was developed. A vaccine that prevents 98% of HPV 6, 11, 16 and 18-associated disease, with a lifetime duration and 85% coverage, in conjunction with current screening was considered.</p> <p>Results</p> <p>Vaccination with screening, compared to screening alone, was associated with an incremental cost-effectiveness ratio of £21,059 per quality adjusted life year (QALY) and £34,687 per life year saved (LYS). More than 400 cases of cervical cancer, 6700 cases of cervical intraepithelial neoplasia and 4750 cases of genital warts could be avoided per 100,000 vaccinated girls. Results were sensitive to assumptions about the need for a booster, the duration of vaccine efficacy and discount rate.</p> <p>Conclusion</p> <p>These analyses suggest that adding a quadrivalent HPV vaccine to current screening in the UK could be a cost-effective method for further reducing the burden of cervical cancer.</p

Buckling Testing and Analysis of Honeycomb Sandwich Panel Arc Segments of a Full-Scale Fairing Barrel

Four honeycomb sandwich panels, representing 1/16th arc segments of a 10 m diameter barrel section of the heavy lift launch vehicle, were manufactured under the NASA Composites for Exploration program and the NASA Constellation Ares V program. Two configurations were chosen for the panels: 6-ply facesheets with 1.125 in. honeycomb core and 8-ply facesheets with 1.000 in. honeycomb core. Additionally, two separate carbon fiber/epoxy material systems were chosen for the facesheets: inautoclave IM7/977-3 and out-of-autoclave T40-800B/5320-1. Smaller 3- by 5-ft panels were cut from the 1/16th barrel sections. These panels were tested under compressive loading at the NASA Langley Research Center. Furthermore, linear eigenvalue and geometrically nonlinear finite element analyses were performed to predict the compressive response of the 3- by 5-ft panels. This manuscript summarizes the experimental and analytical modeling efforts pertaining to the panel composed of 8-ply, T40-800B/5320-1 facesheets (referred to as Panel C). To improve the robustness of the geometrically nonlinear finite element model, measured surface imperfections were included in the geometry of the model. Both the linear and nonlinear, two-dimensional (2-D) and three-dimensional (3-D), models yield good qualitative and quantitative predictions. Additionally, it was predicted correctly that the panel would fail in buckling prior to failing in strength

A Numerical Study on the Effect of Facesheet-Core Disbonds on the Buckling Load of Curved Honeycomb Sandwich Panels

A numerical study on the effect of facesheet-core disbonds on the post-buckling response of curved honeycomb sandwich panels is presented herein. This work was conducted as part of the development of a damage tolerance approach for the next-generation Space Launch System heavy lift vehicle payload fairing. As such, the study utilized full-scale fairing barrel segments as the structure of interest. The panels were composed of carbon fiber reinforced polymer facesheets and aluminum honeycomb core. The panels were analyzed numerically using the finite element method. Facesheet and core nodes in a predetermined circular region were detached to simulate a disbond induced via low-speed impact between the outer mold line facesheet and honeycomb core. Surface-to-surface contact in the disbonded region was invoked to prevent interpenetration of the facesheet and core elements. The diameter of this disbonded region was varied and the effect of the size of the disbond on the post-buckling response was observed. A significant change in the slope of the edge load-deflection response was used to determine the onset of global buckling and corresponding buckling load

Impact of coverage-dependent marginal costs on optimal HPV vaccination strategies

AbstractThe effectiveness of vaccinating males against the human papillomavirus (HPV) remains a controversial subject. Many existing studies conclude that increasing female coverage is more effective than diverting resources into male vaccination. Recently, several empirical studies on HPV immunization have been published, providing evidence of the fact that marginal vaccination costs increase with coverage. In this study, we use a stochastic agent-based modeling framework to revisit the male vaccination debate in light of these new findings. Within this framework, we assess the impact of coverage-dependent marginal costs of vaccine distribution on optimal immunization strategies against HPV. Focusing on the two scenarios of ongoing and new vaccination programs, we analyze different resource allocation policies and their effects on overall disease burden. Our results suggest that if the costs associated with vaccinating males are relatively close to those associated with vaccinating females, then coverage-dependent, increasing marginal costs may favor vaccination strategies that entail immunization of both genders. In particular, this study emphasizes the necessity for further empirical research on the nature of coverage-dependent vaccination costs