Simulated Thrombin Generation in the Presence of Surface-Bound Heparin and Circulating Tissue Factor

An expanded computational model of surface induced thrombin generation was developed that includes hemodynamic effects, 22 biochemical reactions and 44 distinct chemical species. Surface binding of factors V, VIII, IX, and X was included in order to more accurately simulate the formation of the surface complexes tenase and prothrombinase. In order to model these reactions, the non-activated, activated and inactivated forms were all considered. This model was used to investigate the impact of surface bound heparin on thrombin generation with and without the additive effects of thrombomodulin (TM). In total, 104 heparin/TM pairings were evaluated (52 under venous conditions, 52 under arterial conditions), the results demonstrating the synergistic ability of heparin and TM to reduce thrombin generation. Additionally, the role of circulating tissue factor (TF[subscript p]) was investigated and compared to that of surface-bound tissue factor (TF[subscript s]). The numerical results suggest that circulating TF has the power to amplify thrombin generation once the coagulation cascade is already initiated by surface-bound TF. TF[subscript p] concentrations as low as 0.01 nM were found to have a significant impact on total thrombin generation.National Institutes of Health (U.S.) (Grants HL106018 and HL56819

Overlimiting Current and Shock Electrodialysis in Porous Media

Most electrochemical processes, such as electrodialysis, are limited by diffusion, but in porous media, surface conduction and electro-osmotic flow also contribute to ionic fluxes. In this paper, we report experimental evidence for surface-driven over-limiting current (faster than diffusion) and deionization shocks (propagating salt removal) in a porous medium. The apparatus consists of a silica glass frit (1 mm thick with 500 nm mean pore size) in an aqueous electrolyte (CuSO$_4$ or AgNO$_3$) passing ionic current from a reservoir to a cation-selective membrane (Nafion). The current-voltage relation of the whole system is consistent with a proposed theory based on the electro-osmotic flow mechanism over a broad range of reservoir salt concentrations (0.1 mM - 1.0 M), after accounting for (Cu) electrode polarization and pH-regulated silica charge. Above the limiting current, deionized water ($\approx 10 \mu$ $M$) can be continuously extracted from the frit, which implies the existence of a stable shock propagating against the flow, bordering a depleted region that extends more than 0.5mm across the outlet. The results suggest the feasibility of "shock electrodialysis" as a new approach to water desalination and other electrochemical separations.Comment: 39 pages, 9 fig

Electrochemistry and Electrokinetics in Microchannels

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2012.Cataloged from PDF version of thesis.Includes bibliographical references (p. 119-123).The main body of this work considers the design and development of a microfluidic, continuous electrochemical sensor capable of measuring accurate potential differences. The key challenge in creating such a device is the implementation of a miniaturized reference electrode and salt bridge. The purpose of a salt bridge is to allow ionic conduction between the reference and working electrodes while maintaining a physical separation between the two systems. Macro reference electrode and salt bridge techniques are difficult to implement on a micro scale. Instead of attempting to conform one of these techniques to function in a micro system, new methods were developed that take advantage of the conditions in a continuous microfluidic device. In particular, laminar flow and slow relative diffusion times allow for a reference electrode that does not require a physical salt bridge. Ionic conduction is maintained between neighboring reference and analyte streams while slow mixing effectively separates the two systems. Several different device designs were investigated focusing on the prevention of reference electrode contamination. If the reference electrode is chemically contaminated it will no longer behave as expected and can not be used as a reference point. Contamination at the reference electrode was evaluated while varying flow rates and the geometry of the microfluidic device. Mathematical models were simulated in order to understand the mass transport in each device design. Based on these simulations, dimensionless groups were found that defined the dominant physics in each system. These dimensionless numbers were then validated experimentally and numerically over a range of device parameters. Subsequently, operation criteria were developed to ensure that the reference electrode remains stable and uncontaminated. By creating a stable reference electrode on chip, any homogeneous electrochemical system that was previously studied on the macro scale can now be studied continuously in a microfluidic device. A secondary portion of this work investigates the role of surface charge with respect to electrodynamics in a microchannel. As the surface area to volume ratio increases, the concentration of charge at a channel wall may begin to approach the electrolyte concentration in the bulk solution. This phenomenon is studied numerically, with and without convection, in particular as it relates to a possible mechanism for overlimiting current. Additionally, a potential de-ionization device is theorized based on this mechanism along with scaling arguments that can be used to aid device design.by EthelMae Victoria Dydek.Ph.D

Robustness margins and high performance for an adaptive flight control system with application to hypersonic vehicles

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2007.Includes bibliographical references (leaves 59-61).The design tools developed for use with linear controllers such as gain and phase margins do not apply to nonlinear control architectures such as adaptive control. For decades, flight control engineers have used these tools extensively to measure the robustness of their linear control systems and make guarantees on the performance of the closed-loop system in the presence of uncertainties. Stringent demands on performance for safety-critical flight systems, as in the case of hypersonic vehicles, make advanced control methods such as adaptive control increasingly attractive. The major obstacle in the widespread application of adaptive control to such applications is the lack of guarantees on performance and robustness. This thesis presents robustness margins, adaptive control analogs to the linear control notions of gain and phase margins, which can be used to make those guarantees. This paves the way for a systematic Verification and Validation (V&V) approach for adaptive controllers. The operation of an adaptive controller can be broken down into two distinct phases: the adaptation mode, in which the adaptive parameters are varying, and the steady-state mode, in which the adaptive parameters have converged to their steady-state values.(cont.) During the steady-state mode, the nonlinear adaptive controller converges to a linear time-invariant (LTI) system, and many tools exist for the calculation of the requisite margins. However, during the adaptation mode, which is arguably a more crucial mode of operation for the aircraft, no such tools exist. This thesis provides the tools for the numerical calculation of robustness margins during the adaptation mode. Robustness with respect to a range of uncertainties including parametric uncertainties, disturbances, time-delays, unmodeled dynamics, and actuator saturation is derived. The robustness of the adaptive controller is then demonstrated on a fully nonlinear model of a high-performance hypersonic aircraft. The importance of theoretically justified adaptive controllers is illustrated using the historical example of the NASA X-15 research airplane. NASA's three X-15 aircraft together flew nearly 200 flights, acting as test beds for many bleeding-edge technologies, including the nonlinear adaptive controller implemented on the X-15-3. The application of this controller demonstrated the advantages of adaptive control including improved performance and a shorter design cycle.(cont.) However, when the X-15-3 crashed in 1967, one of the severe disadvantages of this early adaptive control was highlighted: the lack of guaranteed stability and performance. Using modern adaptive control theory and the tools developed in this thesis, the control design of the X-15 is revisited and it is demonstrated that had the X-15 controllers been implemented today, all of the 200 flights, without a single exception, would have been performed safely, without incident.by Zachary Thompson Dydek.S.M

Customer Satisfaction Analysis and Proposals for its Improvement

Moje bakalářská práce pojednává o problematice měření a analýzy spokojenosti zákazníků ve společnosti Spedice-Future s.r.o., která je zaměřena na logistickou a dopravní podporu dalším společnostem. Práce vychází z dostupných teoretických východisek týkajících se zákazníka, metod měření jeho spokojenosti a provedených analýz, které představují klíčovou část mé práce. V praktické části je společnost analyzována a na základě dotazníkového průzkumu jsou v práci vyhodnoceny a zpracovány výsledky spokojenosti zákazníka. V závěru jsou dané návrhy na zdokonalení celkové úrovně spokojenosti zákazníka.My thesis deals with the problems of measurement and analysis of customer satisfaction in the company-Future Forwarding Ltd., which is focused on logistical andtransportation support to other companies. The work is based on the available theoretical principles of customer satisfaction measurement methods and the analyzes carried out, which are a key part of my job. In the practical part of the company is first characterized and analyzed on the basis of a question naire are evaluated and processed the work of the results of customer satisfaction. The conclusion containssuggestions for improving the overall level of customer satisfaction.

Assisting dependent people at home through autonomous unmanned aerial vehicles

This work describes a proposal of autonomous unmanned aerial vehicles (AUAVs) for home assistance of dependent people. AUAVs will monitor and recognize human activities during flight to improve their quality of life. However, before bringing such AUAV assistance to real homes, several challenges must be faced to make them viable and practical. Some challenges are technical and some others are related to human factors. In particular, several technical aspects are described for AUAV assistance: (1) flight control, based on our active disturbance rejection control algorithm, (2) flight planning (navigation in obstacle environments), and, (3) processing signals, acquired both from flight-control and monitoring sensors. From the assisted person’s viewpoint, our research focuses on three cues: (1) the user’s perception about AUAV assistance, (2) the influence on human acceptance of AUAV appearance and behavior at home, and (3) the human-robot interaction between assistant AUAV and assisted person. Finally, virtual reality environments are proposed to carry out preliminary tests and user acceptance evaluations.This work has been partially supported by Spanish Ministerio de Ciencia, Innovación y Universidades, Agencia Estatal de Investigaci´on (AEI) / European Regional Development Fund (FEDER, UE) under DPI2016-80894-R grant, and by CIBERSAM of the Instituto de Salud Carlos III. Lidia M. Belmonte holds FPU014/05283 scholarship from Spanish Ministerio de Educaci´on y Formación Profesional

Unnecessary use of fluoroquinolone antibiotics in hospitalized patients

<p>Abstract</p> <p>Background</p> <p>Fluoroquinolones are among the most commonly prescribed antimicrobials and are an important risk factor for colonization and infection with fluoroquinolone-resistant gram-negative bacilli and for <it>Clostridium difficile </it>infection (CDI). In this study, our aim was to determine current patterns of inappropriate fluoroquinolone prescribing among hospitalized patients, and to test the hypothesis that longer than necessary treatment durations account for a significant proportion of unnecessary fluoroquinolone use.</p> <p>Methods</p> <p>We conducted a 6-week prospective, observational study to determine the frequency of, reasons for, and adverse effects associated with unnecessary fluoroquinolone use in a tertiary-care academic medical center. For randomly-selected adult inpatients receiving fluoroquinolones, therapy was determined to be necessary or unnecessary based on published guidelines or standard principles of infectious diseases. Adverse effects were determined based on chart review 6 weeks after completion of therapy.</p> <p>Results</p> <p>Of 1,773 days of fluoroquinolone therapy, 690 (39%) were deemed unnecessary. The most common reasons for unnecessary therapy included administration of antimicrobials for non-infectious or non-bacterial syndromes (292 days-of-therapy) and administration of antimicrobials for longer than necessary durations (234 days-of-therapy). The most common syndrome associated with unnecessary therapy was urinary tract infection or asymptomatic bacteriuria (30% of all unnecessary days-of-therapy). Twenty-seven percent (60/227) of regimens were associated with adverse effects possibly attributable to therapy, including gastrointestinal adverse effects (14% of regimens), colonization by resistant pathogens (8% of regimens), and CDI (4% of regimens).</p> <p>Conclusions</p> <p>In our institution, 39% of all days of fluoroquinolone therapy were unnecessary. Interventions that focus on improving adherence with current guidelines for duration of antimicrobial therapy and for management of urinary syndromes could significantly reduce overuse of fluoroquinolones.</p

Nonlinear Dynamics of Ion Concentration Polarization in Porous Media: The Leaky Membrane Model

The conductivity of highly charged membranes is nearly constant, due to counter-ions screening pore surfaces. Weakly charged porous media, or "leaky membranes", also contain a significant concentration of co-ions, whose depletion at high current leads to ion concentration polarization and conductivity shock waves. To describe these nonlinear phenomena the absence of electro-osmotic flow, a simple Leaky Membrane Model is formulated, based on macroscopic electroneutrality and Nernst-Planck ionic fluxes. The model is solved in cases of unsupported binary electrolytes: steady conduction from a reservoir to a cation-selective surface, transient response to a current step, steady conduction to a flow-through porous electrode, and steady conduction between cation-selective surfaces in cross flow. The last problem is motivated by separations in leaky membranes, such as shock electrodialysis. The article begins with a tribute to Neal Amundson, whose pioneering work on shock waves in chromatography involved similar mathematics