Influence of Material Parameter Variability on the Predicted Coronary Artery Biomechanical Environment via Uncertainty Quantification

Central to the clinical adoption of patient-specific modeling strategies is demonstrating that simulation results are reliable and safe. Simulation frameworks must be robust to uncertainty in model input(s), and levels of confidence should accompany results. In this study we applied a coupled uncertainty quantification-finite element (FE) framework to understand the impact of uncertainty in vascular material properties on variability in predicted stresses. Univariate probability distributions were fit to material parameters derived from layer-specific mechanical behavior testing of human coronary tissue. Parameters were assumed to be probabilistically independent, allowing for efficient parameter ensemble sampling. In an idealized coronary artery geometry, a forward FE model for each parameter ensemble was created to predict tissue stresses under physiologic loading. An emulator was constructed within the UncertainSCI software using polynomial chaos techniques, and statistics and sensitivities were directly computed. Results demonstrated that material parameter uncertainty propagates to variability in predicted stresses across the vessel wall, with the largest dispersions in stress within the adventitial layer. Variability in stress was most sensitive to uncertainties in the anisotropic component of the strain energy function. Unary and binary interactions within the adventitial layer were the main contributors to stress variance, and the leading factor in stress variability was uncertainty in the stress-like material parameter summarizing contribution of the embedded fibers to the overall artery stiffness. Results from a patient-specific coronary model confirmed many of these findings. Collectively, this highlights the impact of material property variation on predicted artery stresses and presents a pipeline to explore and characterize uncertainty in computational biomechanics.Comment: To appear: Biomechanics and Modeling in Mechanobiolog

The status of the world's land and marine mammals: diversity, threat, and knowledge

Knowledge of mammalian diversity is still surprisingly disparate, both regionally and taxonomically. Here, we present a comprehensive assessment of the conservation status and distribution of the world's mammals. Data, compiled by 1700+ experts, cover all 5487 species, including marine mammals. Global macroecological patterns are very different for land and marine species but suggest common mechanisms driving diversity and endemism across systems. Compared with land species, threat levels are higher among marine mammals, driven by different processes (accidental mortality and pollution, rather than habitat loss), and are spatially distinct (peaking in northern oceans, rather than in Southeast Asia). Marine mammals are also disproportionately poorly known. These data are made freely available to support further scientific developments and conservation action

Expert recommendations on the assessment of wall shear stress in human coronary arteries : existing methodologies, technical considerations, and clinical applications

The aim of this manuscript is to provide guidelines for appropriate use of CFD to obtain reproducible and reliable wall shear stress maps in native and instrumented human coronary arteries. The outcome of CFD heavily depends on the quality of the input data, which include vessel geometrical data, proper boundary conditions, and material models. Available methodologies to reconstruct coronary artery anatomy are discussed in ‘Imaging coronary arteries: a brief review’ section. Computational procedures implemented to simulate blood flow in native coronary arteries are presented in ‘Wall shear stress in native arteries’ section. The effect of including different geometrical scales due to the presence of stent struts in instrumented arteries is highlighted in ‘Wall shear stress in stents’ section. The clinical implications are discussed in ‘Clinical applications’ section, and concluding remarks are presented in ‘Concluding remarks’ section

Recent advances in nature conservation in the Lao PDR

The Lao People's Democratic Republic (PDR) has long been a white spot on maps depicting national parks and similar protected areas. This changed dramatically with the official declaration in October 1993 of 18 protected areas covering over 10 per cent of the country's land surface. Among the countries of South East Asia Lao PDR now ranks among those with the highest proportion of land under legal protection. The political climate seems favourable and additional areas may still be added. System planning and, increasingly now, the management of declared areas has been carried out by the Protected Areas and Wildlife Division of the Centre for Protected Areas and Watershed Management (PAWM), Forest Department, with funding by the Swedish International Development Agency (SIDA) and technical support from IUCN-The World Conservation Union. Some of the most vulnerable species, such as the Javan rhinoceros Rhinoceros sondaicus, may already be extirpated, but most species and ecosystems have good prospects of survival if management of the reserves and some wider conservation initiatives can be implemented.</jats:p

Using information graphics in health technology assessment: Toward a structured approach

Objectives: This study investigates the use of information graphics to display the outputs of health technology assessment (HTA) in the United Kingdom and proposes a more structured approach founded in an analysis of the decision-making requirements of the key stakeholders.Methods: A scoping review of HTA reports was conducted to investigate current practice in the use of information graphics in HTA literature. A classification framework using dimensions of report section, graphical type, and originating research center was devised and used for a full content analysis of the graphical figures in the fifty most recent reports produced for the UK National Health Service's HTA process.Results: Our survey shows that graphical tools are used extensively in HTA reports although less frequently than tables. Use of information graphics varies widely between different report sections and tends to follow conventional lines with little evidence of variance from established practice. The largest variance was found between the quantities of graphics used by different research centers responsible for authoring the reports.Conclusions: HTA makes extensive use of graphics; however, there is little evidence of a systematic or standardized approach, or of much innovation. Significant potential exists to explore the application of information graphics in this field, but there are many research challenges. A contextually based, structured approach to the design of effective information graphics in HTA is proposed as a basis both to investigate the application of existing graphical tools in HTA, and to explore the considerable scope for innovation.</jats:p

The rediscovery of the Cebu Flowerpecker <i>Dicaeum Quadricolor</i>, with notes on other forest birds on Cebu, Philippines

SummaryThe Cebu Flowerpecker Dicaeum quadricolor, considered extinct since 1906, was rediscovered in a very small (&lt;2 km2) patch of largely degraded forest near Tabunan, Cebu island, Philippines, in 1992. This patch also holds at least four of the five other bird forms endemic to Cebu that are known to be extant. There appears to be no other forest with any closed canopy elsewhere on the island, and the Tabunan site, although within the Central Cebu National Park, could disappear within five years (through clearance for firewood by local villagers) without immediate intervention.</jats:p

Combined Results from Solution Studies on Intact Influenza Virus M1 Protein and from a New Crystal Form of Its N-Terminal Domain Show That M1 Is an Elongated Monomer

AbstractThe amino-terminal domain of influenza A virus matrix protein (residues 1–164) was crystallized at pH 7 into a new crystal form in space group P1. This packing of the protein implies that M1(1–164) was monomeric in solution when it crystallized. Otherwise, the structure of the M1 fragment in the pH 7 crystals was the same as the monomers in crystals formed at pH 4 where crystal packing resulted in dimer formation [B. Sha and M. Luo, 1997, Nature Struct. Biol. 4, 239–244]. Analysis of intact M1 protein, the N-terminal domain, and the remaining C-terminal fragment (residues 165–252) in solution also showed that the N-terminal domain was monomeric with the same dimensions as determined from the crystal structure. Intact M1 protein was also monomeric but with an elongated shape due to the presence of the C-terminal part. Circular dichroism showed that the C-terminal part of M1 contained helical structure. A model for soluble M1 is presented, based on the assumption that the C-terminal domain is spherical, in which the N- and C-terminal domains are connected by a linker sequence which is available for proteolytic attack

Oligomerization and polymerization of the filovirus matrix protein VP40

AbstractThe matrix protein VP40 from Ebola virus plays an important role in the assembly process of virus particles by interacting with cellular factors, cellular membranes, and the ribonuclearprotein particle complex. Here we show that the N-terminal domain of VP40 folds into a mixture of two different oligomeric states in vitro, namely hexameric and octameric ringlike structures, as detected by gel filtration chromatography, chemical cross-linking, and electron microscopy. Octamer formation depends largely on the interaction with nucleic acids, which in turn confers in vitro SDS resistance. Refolding experiments with a nucleic acid free N-terminal domain preparation reveal a mostly dimeric form of VP40, which is transformed into an SDS resistant octamer upon incubation with E. coli nucleic acids. In addition, we demonstrate that the N-terminal domain of Marburg virus VP40 also folds into ringlike structures, similar to Ebola virus VP40. Interestingly, Marburg virus VP40 rings reveal a high tendency to polymerize into rods composed of stacked rings. These results may suggest distinct roles for different oligomeric forms of VP40 in the filovirus life cycle