Search

Vijay Govindarajan and Anup Srivastava describe six factors that differentiate today’s corporate technology giants from those of the twentieth century, illustrating why professionals should appreciate these differences.

Vijay Govindarajan, Ashish Sood, Anup Srivastava, Luminita Enache, and Barry Mishra have found that companies must focus relentlessly on building long-term competencies, even if doing so reduces immediate profits. Nonetheless, it is vital to shift focus when your product or idea becomes unexpectedly successful, so that you can milk that opportunity’s profits before it vanishes in the face of competition and technological progress.

The cremaster arteriole laser‐induced injury model is a powerful technique with which to investigate the molecular mechanisms that drive thrombus formation. This model is capable of direct visualization and quantification of accumulation of thrombus constituents, including both platelets and fibrin. However, a large degree of variability in platelet accumulation and fibrin formation is observed between thrombi. Strategies to understand this variability will enhance performance and standardization of the model. We determined whether ablation injury size contributes to variation in platelet accumulation and fibrin formation and, if so, whether incorporating ablation injury size into measurements reduces variation.

Supplemental Digital Content is available in the text.

The structure and growth of a blood clot depend on the localization of tissue factor (TF), which can trigger clotting during the hemostatic process or promote thrombosis when exposed to blood under pathological conditions. We sought to understand how the growth, structure, and mechanical properties of clots under flow are shaped by the simultaneously varying TF surface density and its exposure area. We used an eight-channel microfluidic device equipped with a 20- or 100-μm-long collagen surface patterned with lipidated TF of surface densities ∼0.1 and ∼2 molecules/μm2. Human whole blood was perfused at venous shear, and clot growth was continually measured. Using our recently developed computational model of clot formation, we performed simulations to gain insights into the clot’s structure and its resistance to blood flow. An increase in TF exposure area resulted not only in accelerated bulk platelet, thrombin, and fibrin accumulation, but also in increased height of the platelet mass and increased clot resistance to flow. Moreover, increasing the TF surface density or exposure area enhanced platelet deposition by approximately twofold, and thrombin and fibrin generation by greater than threefold, thereby increasing both clot size and its viscous resistance. Finally, TF effects on blood flow occlusion were more pronounced for the longer thrombogenic surface than for the shorter one. Our results suggest that TF surface density and its exposure area can independently enhance both the clot’s occlusivity and its resistance to blood flow. These findings provide, to our knowledge, new insights into how TF affects thrombus growth in time and space under flow.

Introduction:BAV is the most common congenital heart defect affecting ~1.4% of the population. It also brings with it an increased risk of aortopathy, including coarctation, aneurysm, dissection, and accelerated calcification with either stenosis or aortic insufficiency. Quantifying BAV function, altered blood flow, and corresponding hemodynamic forces and their impact on accelerated BAV deterioration improves BAV diagnosis. Predicting how these parameters improve post-interventions may improve surgical predictability and long-term outcome.Methods:A patient-specific modeling protocol based on MRI-based patient data and strongly coupled fluid-structure interaction (FSI) technique was developed to evaluate BAV. Flow via left ventricle, BAV, ascending and descending aorta (Fig A-B) was simulated to obtain biomechanical insights near valve vicinity and study its effects downstream. Diseased anatomy was simulated, and biomechanics compared with virtual interventions that included 1) surgical aortic valve replacement (SAVR), 2) valve sparing root replacement (VSRR) with a sinus graft, and 3) VSRR without sinus graft (Fig C).Results:Our model predictions showed that viscous dissipation (or energy loss) was the greatest in the diseased BAV indicating a high energy loss that substantially reduced post-virtual interventions. Specifically, energy loss reduced by 2.55-, 1.65-, 2.52- folds for SAVR, VSRR-sinus, and VSRR+sinus respectively at peak-systole (Fig. E-H). Interestingly, while SAVR produced the largest orifice area (OA), OA of BAV marginally reduced post VSRR during peak-systole (Fig. I) Conclusions:These studies provide insights into BAV dynamics and may help determine the optimal interventions for a patient. These insights may help improve diagnosis and surgical predictability, optimize treatment, and help with clinical decision making for BAV patients at risk.

Introduction:The Fontan procedure is performed between 2-4 years of age and is a palliative technique for patients born with single ventricle defects. The Fontan physiology is the result of a total cavopulmonary connection between superior and inferior vena cava (SVC and IVC) and the hepatic veins to the pulmonary arteries (PA). Maldistribution of hepatic blood flow to the lungs can result in the formation of pulmonary arteriovenous malformations (PAVM) and resulting cyanosis. Hepatic blood flow distribution (HFD) to right and left lungs is highly dependent on the local flow dynamics. We sought to investigate the impact of SVC-to-IVC flow ratio and age on HFD.Methods:SVC and IVC flow data measured by cardiac MRI (CMR) from 81 Fontan patients were collected to establish the relationship between SVC: IVC flow ratio vs. age. 3D Patient-specific computational fluid dynamics (CFD) modeling was performed for 5 patients who underwent Fontan procedure with an extracardiac conduit to quantify the HFD to the right and left PAs. We evaluated the dependency of HFD on SVC: IVC flow ratio by quantifying HFD to different SVC: IVC flow ratios (2, 1.0, and 0.5) for a given Fontan anatomy.Results:SVC: IVC flow ratio inverted at ~10 years of age (n=81, Figure A) indicating a clear shift to lower body predominance in overall caval flow. CFD analysis (n=5) showed that the shift in SVC-IVC flow had a significant effect on the HFD (Fig. B-F). Change in HFD was more substantial as SVC: IVC flow ratio shifted from 2 to 1 [~5-10 years] with an average % change of 21±6 compared to the HFD change that occurred for a shift of 1 to 0.5 [9±11 for ~10-20 years] (Fig. B-F).Conclusion:Well-balanced distribution of HFD is essential to prevent PAVMs and to ensure long-term efficacy of a Fontan. This study highlights how SVC: IVC flow ratios change over time and can impact HFD to PAs. Interventions to address HFD maldistribution should not be considered in isolation and should incorporate predictions of SVC: IVC changes over time.

Introduction:Mitral valve (MV) leaflet morphology plays an important role insuring efficient, unidirectional blood flow from the left atrium (LA) to ventricle (LV). When treating severe mitral regurgitation (MR), surgical repair, valve replacement, or transcatheter edge-to-edge (E-2-E) repair all provide valid options depending on anatomy and clinical circumstances. These interventions alter the MV morphology, impacting LV filling dynamics. We used fluid-structure interactions (FSI) to evaluate LV filling dynamics after MV interventions, taking into consideration full left-heart (LH) dynamics.Methods:3-D MV model of a patient suffering from severe MR was reconstructed from echocardiographic data. A LH wall motion algorithm was developed and applied to CT-derived LA and LV walls to realistically represent LH dynamics. LH wall motion, MV dynamics and blood flow in LA and LV during MV function was simulated using a strongly coupled fluid structure interaction approach. Virtual interventions using a surgical 33mm bioprosthetic valve (BPV) and transcatheter E-2-E repair were performed and evaluated.Results:Our FSI model predicted a physiological vortex ring developing in the LV for the pre-op MV during early diastole. BPV produced complex asymmetrical vortices. Due to its double orifice, the E-2-E clip produced two separate vortex rings with the largest velocity magnitude. Of all the three treatments, BPV had the greatest leaflet deformation rate.Conclusion:This model provides realistic quantitative insights into post-op filling dynamics that can be used to personalize and optimize valve intervention. These methodologies may help clinicians to realistically predict and evaluate patient-specific LV filling dynamics to tailor MV interventions.

A comprehensive understanding of thrombus formation as a physicochemical process that has evolved to protect the integrity of the human vasculature is critical to our ability to predict and control pathological states caused by a malfunctioning blood coagulation system. Despite numerous investigations, the spatial and temporal details of thrombus growth as a multicomponent process are not fully understood. Here, we used computational modeling to investigate the temporal changes in the spatial distributions of the key enzymatic (i.e., thrombin) and structural (i.e., platelets and fibrin) components within a growing thrombus. Moreover, we investigated the interplay between clot structure and its mechanical properties, such as hydraulic resistance to flow. Our model relied on the coupling of computational fluid dynamics and biochemical kinetics, and was validated using flow-chamber data from a previous experimental study. The model allowed us to identify the distinct patterns characterizing the spatial distributions of thrombin, platelets, and fibrin accumulating within a thrombus. Our modeling results suggested that under the simulated conditions, thrombin kinetics was determined predominantly by prothrombinase. Furthermore, our simulations showed that thrombus resistance imparted by fibrin was ∼30-fold higher than that imparted by platelets. Yet, thrombus-mediated bloodflow occlusion was driven primarily by the platelet deposition process, because the height of the platelet accumulation domain was approximately twice that of the fibrin accumulation domain. Fibrinogen supplementation in normal blood resulted in a nonlinear increase in thrombus resistance, and for a supplemented fibrinogen level of 48%, the thrombus resistance increased by ∼2.7-fold. Finally, our model predicted that restoring the normal levels of clotting factors II, IX, and X while simultaneously restoring fibrinogen (to 88% of its normal level) in diluted blood can restore fibrin generation to ∼78% of its normal level and hence improve clot formation under dilution.

This study presents a new approach to the formulation of functional nanofluids with high solid loading and low viscosity while retaining the surface activity of nanoparticles, in particular, their electrochemical response. The proposed methodology can be applied to a variety of functional nanomaterials and enables exploration of nanofluids as a medium for industrial applications beyond heat transfer fluids, taking advantage of both liquid behavior and functionality of dispersed nanoparticles. The highest particle concentration achievable with pristine 25 nm titania (TiO2) nanoparticles in aqueous electrolytes (pH 11) is 20 wt %, which is limited by particle aggregation and high viscosity. We have developed a scalable one-step surface modification procedure for functionalizing those TiO2nanoparticles with a monolayer coverage of propyl sulfonate groups, which provides steric and charge-based separation of particles in suspension. Stable nanofluids with TiO2loadings up to 50 wt % and low viscosity are successfully prepared from surface-modified TiO2nanoparticles in the same electrolytes. Viscosity and thermal conductivity of the resulting nanofluids are evaluated and compared to nanofluids prepared from pristine nanoparticles. Furthermore, it is demonstrated that the surface-modified titania nanoparticles retain more than 78% of their electrochemical response as compared to that of the pristine material. Potential applications of the proposed nanofluids include, but are not limited to, electrochemical energy storage and catalysis, including photo- and electrocatalysis.

The article provides information on Stasis Labs, launched by Dinesh Seemakurty and Michael Maylahn. Topics discussed include manufacturing of medical systems that could deliver vital signs of patients directly on clinicians' smartphones; maintaining quality and cost of products; and growth in emerging markets.

No relevant conflicts of interest to declare.

The growth of a blood clot is initiated by tissue factor (TF) exposure and is expected to depend on TF localization (i.e., its level and spatial distribution). We sought to understand how the structural and mechanical properties of clots under flow are shaped by simultaneously varying the surface density of TF and its area of exposure. We used a microfluidic device harboring thrombogenic surfaces that differed in length and TF surface density. We perfused human whole blood through this device and continually measured platelet deposition, thrombin formation, and fibrin accumulation by means of fluorescence microscopy. Using our recently developed, detailed mathematical model of spatial clot growth under flow, we performed computational simulations to gain insights into the connection between the structure of a clot and its mechanical properties, such as resistance to blood flow and flow axial velocity.

The article discusses the emergence of process innovation as a sound means to strategize enterprise management. Information technology is considered as the economy's most powerful tool for productivity growth. Leading IT departments have been adept at finding ways to automate information flows and streamline processes. At the back end of the innovation process, three fundamental challenges exist, and they are: forgetting, borrowing, and learning. To tackle these challenges means to create tension.