Risks and Benefits of Using a Commercially Available Ventricular Assist Device for Failing Fontan Cavopulmonary Support: A Modeling Investigation

Fontan patients often develop circulatory failure and are in desperate need of a therapeutic solution. A blood pump surgically placed in the cavopulmonary pathway can substitute the function of the absent sub-pulmonary ventricle by generating a mild pressure boost. However, there is currently no commercially available device designed for the cavopulmonary application; and the risks and benefits of implanting a ventricular assist device (VAD), originally designed for the left ventricular application, on the right circulation of failing Fontan patients is not yet clear. Moreover, further research is needed to compare the hemodynamics between the two clinically-considered surgical configurations for cavopulmonary assist, with Full and inferior vena cava (IVC) support corresponding to the entire venous return or only the inferior venous return, respectively, being routed through the VAD. In this study, we used a numerical model of the failing Fontan physiology to evaluate the Fontan hemodynamic response to a left VAD during the IVC and Full support scenarios. We observed that during Full support, the VAD improved the cardiac output while maintaining blood pressures within safe ranges, and lowered the IVC pressure to \u3c15 mmHg; however, we found a potential risk of lung damage at higher pump speeds due to the excessive pulmonary pressure elevation. IVC support, on the other hand, did not benefit the hemodynamics in the patient cases simulated, resulting in the superior vena cava pressure increasing to an unsafe level of \u3e20 mmHg. The findings in this study may be helpful to surgeons for recognizing the risks of a cavopulmonary VAD and developing coherent clinical strategies for the implementation of cavopulmonary support

Risks and Benefits of Using a Commercially Available Ventricular Assist Device for Failing Fontan Cavopulmonary Support: A Modeling Investigation

Fontan patients often develop circulatory failure and are in desperate need of a therapeutic solution. A blood pump surgically placed in the cavopulmonary pathway can substitute the function of the absent sub-pulmonary ventricle by generating a mild pressure boost. However, there is currently no commercially available device designed for the cavopulmonary application; and the risks and benefits of implanting a ventricular assist device (VAD) originally designed for the left ventricular application on the right circulation of failing Fontan patients is not yet clear. Moreover, further research is needed to compare the hemodynamics between the two clinically-considered surgical configurations (Full Support and IVC Support) for cavopulmonary assist, with Full and IVC Support corresponding to the entire venous return or only the inferior venous return, respectively, being routed through the VAD. In this study, we used a numerical model of the failing Fontan physiology to evaluate the Fontan hemodynamic response to a left VAD during the IVC and Full supports. We observed that during the Full support the VAD improved the cardiac output while maintaining blood pressures within safe ranges, and lowered the IVC pressure to <15mmHg; however, we found a potential risk of lung damage at higher pump speeds due to the excessive pulmonary pressure elevation. IVC support the other hand, did not benefit the hemodynamics of the example failing Fontan patients, resulting in the superior vena cava pressure increasing to an unsafe level of >20 mmHg. The findings in this study may be helpful to surgeons for recognizing the risks of a cavopulmonary VAD and developing coherent clinical strategies for the implementation of cavopulmonary support

Target Flow-Pressure Operating Range for Designing a Failing Fontan Cavopulmonary Support Device

Fontan operation as the current standard of care for the palliation of single ventricle defects results in significant late complications. Using a mechanical circulatory device for the right circulation to serve the function of the missing subpulmonary ventricle could potentially stabilize the failing Fontan circulation. This study aims to elucidate the hydraulic operating regions that should be targeted for designing cavopulmonary blood pumps. By integrating numerical analysis and available clinical information, the interaction of the cavopulmonary support via the IVC and full assist configurations with a wide range of simulated adult failing scenarios was investigated; with IVC and full assist corresponding to the inferior venous return or the entire venous return, respectively, being routed through the device. We identified the desired hydraulic operating regions for a cavopulmonary assist device by clustering all head pressures and corresponding pump flows that result in hemodynamic improvement for each simulated failing Fontan physiology. Results show that IVC support can produce beneficial hemodynamics in only a small fraction of failing Fontan scenarios. Cavopulmonary assist device could increase cardiac index by 35% and decrease the inferior vena cava pressure by 45% depending on the patient\u27s pre-support hemodynamic state and surgical configuration of the cavopulmonary assist device (IVC or full support). The desired flow-pressure operating regions we identified can serve as the performance criteria for designing cavopulmonary assist devices as well as evaluating off-label use of commercially available left-side blood pumps for failing Fontan cavopulmonary support

Establishing Physical Survivability of Large Networks using Properties of Two-Connected Graphs

Establishing the physical survivability of large networks is not a trivial task. Some techniques for assessing physical survivability such as the cutset method can not deal with large size networks (S. Ramamurthy and B. Mukherjee), (W.N. Grover and J. Doucette, 2001). A fast technique for finding biconnected components of a graph and testing the network for node-/link-bridges, presented in (W.D. Grover, 2004), does not provide any further information, such as identifying the fundamental cycles within the network, which would significantly benefit the next phase of network design for protection using such techniques as shared backup path protection (SBPP), p-cycle, or ring protection (W.D. Grover, 2004). This paper presents an alternative technique, based on graph theory, for evaluating the physical survivability of networks. This technique can deal with network sizes of many thousand nodes, with computational times which are comparable with the biconnected components method, whilst providing more information about the susceptibility of a network to individual link and node failures in preparation for the next phase of network protection design

Survival of Hendra Virus in the Environment: Modelling the Effect of Temperature

Hendra virus (HeV), a highly pathogenic zoonotic paramyxovirus recently emerged from bats, is a major concern to the horse industry in Australia. Previous research has shown that higher temperatures led to lower virus survival rates in the laboratory. We develop a model of survival of HeV in the environment as influenced by temperature. We used 20 years of daily temperature at six locations spanning the geographic range of reported HeV incidents to simulate the temporal and spatial impacts of temperature on HeV survival. At any location, simulated virus survival was greater in winter than in summer, and in any month of the year, survival was higher in higher latitudes. At any location, year-to-year variation in virus survival 24 h post-excretion was substantial and was as large as the difference between locations. Survival was higher in microhabitats with lower than ambient temperature, and when environmental exposure was shorter. The within-year pattern of virus survival mirrored the cumulative within-year occurrence of reported HeV cases, although there were no overall differences in survival in HeV case years and non-case years. The model examines the effect of temperature in isolation; actual virus survivability will reflect the effect of additional environmental factor

Probing the inter-layer exciton physics in a MoS2_2/MoSe2_2/MoS2_2 van der Waals heterostructure

Stacking atomic monolayers of semiconducting transition metal dichalcogenides (TMDs) has emerged as an effective way to engineer their properties. In principle, the staggered band alignment of TMD heterostructures should result in the formation of inter-layer excitons with long lifetimes and robust valley polarization. However, these features have been observed simultaneously only in MoSe$_2$/WSe$_2$ heterostructures. Here we report on the observation of long lived inter-layer exciton emission in a MoS$_2$/MoSe$_2$/MoS$_2$ trilayer van der Waals heterostructure. The inter-layer nature of the observed transition is confirmed by photoluminescence spectroscopy, as well as by analyzing the temporal, excitation power and temperature dependence of the inter-layer emission peak. The observed complex photoluminescence dynamics suggests the presence of quasi-degenerate momentum-direct and momentum-indirect bandgaps. We show that circularly polarized optical pumping results in long lived valley polarization of inter-layer exciton. Intriguingly, the inter-layer exciton photoluminescence has helicity opposite to the excitation. Our results show that through a careful choice of the TMDs forming the van der Waals heterostructure it is possible to control the circular polarization of the inter-layer exciton emission.Comment: 19 pages, 3 figures. Just accepted for publication in Nano Letters (http://pubs.acs.org/doi/10.1021/acs.nanolett.7b03184

Survival of Hendra Virus in the Environment: Modelling the Effect of Temperature

Hendra virus (HeV), a highly pathogenic zoonotic paramyxovirus recently emerged from bats, is a major concern to the horse industry in Australia. Previous research has shown that higher temperatures led to lower virus survival rates in the laboratory. We develop a model of survival of HeV in the environment as influenced by temperature. We used 20 years of daily temperature at six locations spanning the geographic range of reported HeV incidents to simulate the temporal and spatial impacts of temperature on HeV survival. At any location, simulated virus survival was greater in winter than in summer, and in any month of the year, survival was higher in higher latitudes. At any location, year-to-year variation in virus survival 24 h post-excretion was substantial and was as large as the difference between locations. Survival was higher in microhabitats with lower than ambient temperature, and when environmental exposure was shorter. The within-year pattern of virus survival mirrored the cumulative within-year occurrence of reported HeV cases, although there were no overall differences in survival in HeV case years and non-case years. The model examines the effect of temperature in isolation; actual virus survivability will reflect the effect of additional environmental factor

The CAPM strikes back? An equilibrium model with disasters

Embedding disasters into a general equilibrium model with heterogeneous firms induces strong nonlinearity in the pricing kernel, helping explain the empirical failure of the (consumption) CAPM. Our single-factor model reproduces the failure of the CAPM in explaining the value premium in finite samples without disasters and its relative success in samples with disasters. Due to beta measurement errors, the estimated beta-return relation is flat, consistent with the beta “anomaly,” even though the true beta-return relation is strongly positive. Finally, the consumption CAPM fails in simulations, even though a nonlinear model with the true pricing kernel holds exactly by construction