The 2014 Ebola virus (EBOV) outbreak in West Africa is the largest in recorded history and resulted in over 11,000 deaths. It is essential that strategies for treatment and containment be developed to avoid future epidemics of this magnitude. With the development of vaccines and antibody-based therapies using the envelope glycoprotein (GP) of the 1976 Mayinga strain, one important strategy is to anticipate how the evolution of EBOV might compromise these efforts. In this study we have initiated a watch list of potential antibody escape mutations of EBOV by modeling interactions between GP and the antibody KZ52. The watch list was generated using molecular modeling to estimate stability changes due to mutation. Every possible mutation of GP was considered and the list was generated from those that are predicted to disrupt GP-KZ52 binding but not to disrupt the ability of GP to fold and to form trimers. The resulting watch list contains 34 mutations (one of which has already been seen in humans) at six sites in the GP2 subunit. Should mutations from the watch list appear and spread during an epidemic, it warrants attention as these mutations may reflect an evolutionary response from the virus that could reduce the effectiveness of interventions such as vaccination. However, this watch list is incomplete and emphasizes the need for more experimental structures of EBOV interacting with antibodies in order to expand the watch list to other epitopes. We hope that this work provokes experimental research on evolutionary escape in both Ebola and other viral pathogens.
The purpose of this study was to investigate the utility of exploratory analytical techniques using publically available data in informing interventions in case of infectious diseases outbreaks. More exactly spatiotemporal and multivariate methods were used to characterize the dynamics of the Ebola Virus Disease (EVD) epidemic in West Africa, and propose plausible relationships with demographic/social risk factors. The analysis showed that there was significant spatial, temporal, and spatiotemporal dependence in the evolution of the disease. For the first part of the epidemic, the cases were highly clustered in a few administrative units, in the proximity of the point of origin of the outbreak, possibly offering the opportunity to stop the spread of the disease. Later in the epidemic, high clusters were observed, but only in Liberia and Sierra Leone. Although not definitely factors of risk, in the setting in which the epidemic arose, our analysis suggests infrastructure, access to and use of health services, and connectivity possibly accelerated and magnified the spread of EVD. Also, the spatial, temporal, and spatiotemporal patterns of epidemic can be clearly shown - with evident application in the early stages of management of epidemics. In particular, we found that the spatial-temporal analytic tool SaTScan may be used effectively during the evolution of an epidemic to identify areas for targeted intervention. In the case of EVD epidemic in West Africa, better data and integration local knowledge and customs may have been more useful to recognize the proper response.
We hypothesized that RFA-induced muscle damage in the left atrium can be visualized by implementing two different modalities of Hyperspectral Imaging (HSI) technology. HSI captures the entire spectrum for each pixel in an image. Post-acquisition analysis is used to reveal the main spectral components present in the sample to spatially separate regions in the image based on their spectra. Methods: Ablations were performed on a freshly excised porcine left atrial tissue. Images were acquired between 420-720 nm at a spatial resolution of 1392x1040 pixels, using a commercial HSI system (Nuance FX, PerkinElmer) fitted with a low magnification lens. UV LED (365nm) was used to illuminate samples for autofluorescence HSI datasets, while white light source was used for reflectance-based HSI experiments. Nonlinear unmixing was used to reveal the main spectral components and identify lesions sites. Results: Both HSI modalities greatly enhanced RF lesion visualization. The side by side comparison included: i) signal-to-noise ratio of the lesion component intensity profiles, ii) the optimum acquisition ranges and iii) the minimum number of wavelengths needed to differentiate between ablated and unablated tissue. Conclusion: The data provide technical basis for developing HSI catheter aiding real-time RFA lesion visualization during surgical ablation of AF.
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