A Study of Different Modeling Choices For Simulating Platelets Within the Immersed Boundary Method

The Immersed Boundary (IB) method is a widely-used numerical methodology for the simulation of fluid-structure interaction problems. The IB method utilizes an Eulerian discretization for the fluid equations of motion while maintaining a Lagrangian representation of structural objects. Operators are defined for transmitting information (forces and velocities) between these two representations. Most IB simulations represent their structures with piecewise-linear approximations and utilize Hookean spring models to approximate structural forces. Our specific motivation is the modeling of platelets in hemodynamic flows. In this paper, we study two alternative representations - radial basis functions (RBFs) and Fourier-based (trigonometric polynomials and spherical harmonics) representations - for the modeling of platelets in two and three dimensions within the IB framework, and compare our results with the traditional piecewise-linear approximation methodology. For different representative shapes, we examine the geometric modeling errors (position and normal vectors), force computation errors, and computational cost and provide an engineering trade-off strategy for when and why one might select to employ these different representations.Comment: 33 pages, 17 figures, Accepted (in press) by APNU

Quantum Ontologies and Mind-Matter Synthesis

Aspects of a quantum mechanical theory of a world containing efficacious mental aspects that are closely tied to brains, but that are not identical to brains.Comment: 69 pages. Invited contribution to Xth Max Born Symposium: "Quantum Future". Published in "Quantum Future", eds. P. Blanchard and A. Jadczyk, Springer-Verlag, 1999, ISBN 3-540-65218-3. LBNL 4072

Sedimentation and Flow Through Porous Media: Simulating Dynamically Coupled Discrete and Continuum Phases

We describe a method to address efficiently problems of two-phase flow in the regime of low particle Reynolds number and negligible Brownian motion. One of the phases is an incompressible continuous fluid and the other a discrete particulate phase which we simulate by following the motion of single particles. Interactions between the phases are taken into account using locally defined drag forces. We apply our method to the problem of flow through random media at high porosity where we find good agreement to theoretical expectations for the functional dependence of the pressure drop on the solid volume fraction. We undertake further validations on systems undergoing gravity induced sedimentation.Comment: 22 pages REVTEX, figures separately in uudecoded, compressed postscript format - alternatively e-mail '[email protected]' for hardcopies

From mindless masses to small groups: Conceptualizing collective behavior in crowd modeling.

Computer simulations are increasingly used to monitor and predict behavior at large crowd events, such as mass gatherings, festivals and evacuations. We critically examine the crowd modeling literature and call for future simulations of crowd behavior to be based more closely on findings from current social psychological research. A systematic review was conducted on the crowd modeling literature (N = 140 articles) to identify the assumptions about crowd behavior that modelers use in their simulations. Articles were coded according to the way in which crowd structure was modeled. It was found that 2 broad types are used: mass approaches and small group approaches. However, neither the mass nor the small group approaches can accurately simulate the large collective behavior that has been found in extensive empirical research on crowd events. We argue that to model crowd behavior realistically, simulations must use methods which allow crowd members to identify with each other, as suggested by self-categorization theory

Effect of tube diameter and capillary number on platelet margination and near-wall dynamics

The effect of tube diameter $D$ and capillary number $Ca$ on platelet margination in blood flow at $\approx 37\%$ tube haematocrit is investigated. The system is modelled as three-dimensional suspension of deformable red blood cells and nearly rigid platelets using a combination of the lattice-Boltzmann, immersed boundary and finite element methods. Results show that margination is facilitated by a non-diffusive radial platelet transport. This effect is important near the edge of the cell-free layer, but it is only observed for $Ca > 0.2$, when red blood cells are tank-treading rather than tumbling. It is also shown that platelet trapping in the cell-free layer is reversible for $Ca \leq 0.2$. Only for the smallest investigated tube ($D = 10 \mu\text{m}$) margination is essentially independent of $Ca$. Once platelets have reached the cell-free layer, they tend to slide rather than tumble. The tumbling rate is essentially independent of $Ca$ but increases with $D$. Tumbling is suppressed by the strong confinement due to the relatively small cell-free layer thickness at $\approx 37\%$ tube haematocrit.Comment: 16 pages, 10 figure

Surrounded by sound: noise, rights and environments

Noise was probably the first environmental pollutant (apart from human waste) in the Ancient world. Yet today, by comparison with other environmental matters, noise and protection from its effects are often overlooked, except in specialist fields such as architecture or planning. One major reason for this may be that noise does not possess the same ability to spread that is characteristic of other forms of pollution. Noise is also an unusual form of environmental pollution in having a physical impact – it is ‘heard’ and can be ‘felt’ – but is predominantly interpreted subjectively. The impact and consequences of anthropogenic noise for humans and biodiversity in general, are currently under-investigated in criminology and are under-addressed in both public and private international environmental law. Here we question why noise has not (so far) been explored within green criminology and only tentatively explored within cultural criminology. The objectives are to provide an overview of noise as a topic, connecting media, culture, anti- and pro-social behaviour, and to unearth interconnections between the matter of noise and its implications for the environment

Elevated hematocrit enhances platelet accumulation following vascular injury

Red blood cells (RBCs) demonstrate procoagulant properties in vitro, and elevated hematocrit is associated with reduced bleeding and increased thrombosis risk in humans. These observations suggest RBCs contribute to thrombus formation. However, effects of RBCs on thrombosis are difficult to assess because humans and mice with elevated hematocrit typically have coexisting pathologies. Using an experimental model of elevated hematocrit in healthy mice, we measured effects of hematocrit in 2 in vivo clot formation models. We also assessed thrombin generation, platelet-thrombus interactions, and platelet accumulation in thrombi ex vivo, in vitro, and in silico. Compared with controls, mice with elevated hematocrit (RBCHIGH) formed thrombi at a faster rate and had a shortened vessel occlusion time. Thrombi in control and RBCHIGH mice did not differ in size or fibrin content, and there was no difference in levels of circulating thrombin-antithrombin complexes. In vitro, increasing the hematocrit increased thrombin generation in the absence of platelets; however, this effect was reduced in the presence of platelets. In silico, direct numerical simulations of whole blood predicted elevated hematocrit increases the frequency and duration of interactions between platelets and a thrombus.Whenhumanwhole blood was perfused over collagen at arterial shear rates, elevating the hematocrit increased the rate of platelet deposition and thrombus growth. These data suggest RBCs promote arterial thrombosis by enhancing platelet accumulation at the site of vessel injury. Maintaining a normal hematocrit may reduce arterial thrombosis risk in humans

Cesarean delivery on maternal request: Can the ethical problem be solved by the principlist approach?

In this article, we use the principlist approach to identify, analyse and attempt to solve the ethical problem raised by a pregnant woman's request for cesarean delivery in absence of medical indications

Regulation of early steps of GPVI signal transduction by phosphatases: a systems biology approach

We present a data-driven mathematical model of a key initiating step in platelet activation, a central process in the prevention of bleeding following Injury. In vascular disease, this process is activated inappropriately and causes thrombosis, heart attacks and stroke. The collagen receptor GPVI is the primary trigger for platelet activation at sites of injury. Understanding the complex molecular mechanisms initiated by this receptor is important for development of more effective antithrombotic medicines. In this work we developed a series of nonlinear ordinary differential equation models that are direct representations of biological hypotheses surrounding the initial steps in GPVI-stimulated signal transduction. At each stage model simulations were compared to our own quantitative, high-temporal experimental data that guides further experimental design, data collection and model refinement. Much is known about the linear forward reactions within platelet signalling pathways but knowledge of the roles of putative reverse reactions are poorly understood. An initial model, that includes a simple constitutively active phosphatase, was unable to explain experimental data. Model revisions, incorporating a complex pathway of interactions (and specifically the phosphatase TULA-2), provided a good description of the experimental data both based on observations of phosphorylation in samples from one donor and in those of a wider population. Our model was used to investigate the levels of proteins involved in regulating the pathway and the effect of low GPVI levels that have been associated with disease. Results indicate a clear separation in healthy and GPVI deficient states in respect of the signalling cascade dynamics associated with Syk tyrosine phosphorylation and activation. Our approach reveals the central importance of this negative feedback pathway that results in the temporal regulation of a specific class of protein tyrosine phosphatases in controlling the rate, and therefore extent, of GPVI-stimulated platelet activation

Design of a multicentered randomized controlled trial on the clinical and cost effectiveness of schema therapy for personality disorders

<p>Abstract</p> <p>Background</p> <p>Despite international guidelines describing psychotherapy as first choice for people with personality disorders (PDs), well-designed research on the effectiveness and cost-effectiveness of psychotherapy for PD is scarce. Schema therapy (ST) is a specific form of psychological treatment that proved to be effective for borderline PD. Randomized controlled studies on the effectiveness of ST for other PDs are lacking. Another not yet tested new specialized treatment is Clarification Oriented Psychotherapy (COP). The aim of this project is to perform an effectiveness study as well as an economic evaluation study (cost effectiveness as well as cost-utility) comparing ST versus COP versus treatment as usual (TAU). In this study, we focus on avoidant, dependent, obsessive-compulsive, paranoid, histrionic and narcissistic PD.</p> <p>Methods/Design</p> <p>In a multicentered randomized controlled trial, ST, and COP as an extra experimental condition, are compared to TAU. Minimal 300 patients are recruited in 12 mental health institutes throughout the Netherlands, and receive an extensive screening prior to enrolment in the study. When eligible, they are randomly assigned to one of the intervention groups. An economic evaluation and a qualitative research study on patient and therapist perspectives on ST are embedded in this trial. Outcome assessments (both for clinical effectiveness and economic evaluation) take place at 6,12,18,24 and 36 months after start of treatment. Primary outcome is recovery from PD; secondary measures include general psychopathological complaints, social functioning and quality of life. Data for the cost-effectiveness and cost-utility analyses are collected by using a retrospective cost interview. Information on patient and therapist perspectives is gathered using in-depth interviews and focus groups, and focuses on possible helpful and impeding aspects of ST.</p> <p>Discussion</p> <p>This trial is the first to compare ST and COP head-to-head with TAU for people with a cluster C, paranoid, histrionic and/or narcissistic PD. By combining clinical effectiveness data with an economic evaluation and with direct information from primary stakeholders, this trial offers a complete and thorough view on ST as a contribution to the improvement of treatment for this PD patient group.</p> <p>Trial registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=566">NTR566</a></p