A wave propagation model of blood flow in large vessels using an approximate velocity profile functionLumped-parameter models (zero-dimensional) and wave-propagation models (onedimensional) for pressure and flow in large vessels, as well as fully three-dimensional fluid-structure interaction models for pressure and velocity, can contribute valuably to answering physiological and patho-physiological questions that arise in the diagnostics and treatment of cardiovascular diseases. Lumped-parameter models are of importance mainly for the modelling of the complete cardiovascular system but provide little detail on local pressure and flow wave phenomena. Fully threedimensional fluid-structure interaction models consume a large amount of computer time and must be provided with suitable boundary conditions that are often not known. One-dimensional wave-propagation models in the frequency and time domain are well suited to obtaining clinically relevant information on local pressure and flow waves travelling through the arterial system. They can also be used to provide boundary conditions for fully three-dimensional models, provided that they are defined in, or transferred to, the time domain.Most of the one-dimensional wave propagation models in the time domain described in the literature assume velocity profiles and therefore frictional forces to be in phase with the flow, whereas from exact solutions in the frequency domain a phase difference between the flow and the wall shear stress is known to exist. In this study an approximate velocity profile function more suitable for one-dimensional wave propagation is introduced and evaluated. It will be shown that this profile function provides first-order approximations for the wall shear stress and the nonlinear term in the momentum equation, as a function of local flow and pressure gradient in the time domain. The convective term as well as the approximate friction term are compared to their counterparts obtained from Womersley profiles and show good agreement in the complete range of the Womersley parameter α. In the limiting cases, for Womersley parameters α → 0 and α → ∞, they completely coincide. It is shown that in one-dimensional wave propagation, the friction term based on the newly introduced approximate profile function is important when considering pressure and flow wave propagation in intermediate-sized vessels.

Polymers show great potential as a durable and high density alternative for data storage and for this purpose the natural polymer DNA has already attracted much interest from researchers. A DNA based storage system, which makes use of the four nucleotides to store binary codes, is more durable and can store information with a much higher density than conventional storage systems. Synthetic polymers have properties that make them even more suitable for data storage, at least in principle, if complete control over their composition, i.e. monomer sequence can be obtained. This review addresses the current status of data storage in DNA, proteins, and synthetic polymers, with the objective to overcome the problems of the current data storage technology. Written records are crucial for our understanding of past civilizations. They are so important, that we commonly define "history" as the study of the past as it is described in written documents, and refer to earlier events as "prehistory". The main reason why we know so much about certain past civilizations is that they used durable media to store their writings and art. Thus we learned about old civilizations in Mesopotamia through 5,300-year-old clay tablets from Uruk that have been preserved until today, we learned about the late Shang dynasty (c. 1200-1050 BC) from China through inscriptions on oracle bones, and about the Olmec civilization in Mexico through the Cascajal Block, a stone slab with 3,000-year-old writing made of serpentinite 1. Digital data has completely changed the way we write, use, and access information nowadays and we live in what is commonly referred to as the 'digital world.' It is expected that the need for digital information will continue to grow, reaching the level of 44 trillion gigabytes in 2020 2-5. However, current data storage suffers from digital obsolescence: although the bits and bytes of the digital world are eternal, at least in principle, the storage devices are not. They deteriorate over time, usually within a few decades. For instance, memory cards and chips are maintainable for circa 10 years, while standard hard drives are susceptible to magnetic fields, high temperatures, and mechanical failures 6-8. The decay of the storage media results in data loss, which is currently prevented by a constant shuffling of data between different devices and facilities. Due to the explosion of digital data, there is a constant need to migrate to new technologies that do not always support the old technologies 9. Hence much of the information that we have stored on floppy disks, tapes, CD-ROMS, spinning hard drives and flash memory will soon be lost forever. And the challenges do not stop here. Current storage technologies require significant space and enormous amounts of energy 10. The world data centers currently consume annually ca. 420

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Purpose: Hereditary head and neck paraganglioma (HNPGL) syndromes are associated with mutations in the SDHD(PGL1), SDHC(PGL3), and SDHB(PGL4) genes encoding succinate dehydrogenase subunits. We recently described mutations in a previously uncharacterized human gene, now called SDHAF2, and showed that this was the long-sought "imprinted" PGL2 gene. Here, we present a new branch of the Dutch SDHAF2 (PLG2-SDH5) family.Experimental Design: The SDHAF2 family has been collected over a 30-year period. The family described here was linked to PGL2 and at-risk family members were invited to participate in this study. Patients were investigated and treated dependent on tumor size and localization. All family members have now been analyzed for the SDHAF2 mutation status.Results: Among the 57 family members, 23 were linkage positive including 7 risk-free carriers (maternal imprinting). Of the 16 at-risk individuals, 11 had a total of 24 tumors with primarily carotid (71%) and vagal locations (17%). Multifocality of tumors was prominent (91%). Malignancy was not detected. The average age at onset was 33 years, and many patients (42%) were asymptomatic prior to screening. SDHAF2 mutation analysis confirmed the findings of the previously performed linkage analysis without detection of discrepancies.Conclusions: We established the SDHAF2 mutation status of PGL2 family members. Phenotypic characterization of this family confirms the currently exclusive association of SDHAF2 mutations with HNPGL. This SDHAF2 family branch shows a young age at onset and very high levels of multifocality. A high percentage of patients were asymptomatic at time of detection.

In many Western countries, hospital emergency departments are overcrowded, leading to the desire to strengthen primary care, particularly after hours. To achieve this goal, an increasing number of Western nations are reorganizing their after-hours primary care systems into large-scale primary care physician (PCP) cooperatives. This article provides an overview of the organization, performance, and development of PCP cooperatives in the Netherlands. The Dutch after-hours primary care system might offer opportunities for other countries facing problems with after-hours care and inappropriate emergency department visits. During the past several years, the number of contacts with Dutch PCP cooperatives has increased to 245 contacts per 1000 citizens per year. Many contacts (45%) are nonurgent, and about half occur as part of a series of primary care contacts. Low accessibility and availability of daytime primary care are related to greater use of after-hours primary care. To prevent unnecessary attendance at the cooperatives, physicians advocate copayment, a stricter triage system, and a larger role for telephone doctors. More than half of the PCP cooperatives in the Netherlands have integrated with hospital emergency departments, forming "emergency care access points." This collaboration has decreased emergency department use by 13% to 22%, and treatment of self-referrals by PCP cooperatives in emergency care access points is safe and cost-effective. Direct access to diagnostic facilities may optimize efficiency even more. Other recent developments include access to electronic health records of daytime primary care practices, task substitution from physicians to nurses, and the launch of a 2-year training program for PCPs to become experts in emergency care.

Vascular tissue engineering represents a promising approach for the development of living small-diameter vascular grafts that can be used for replacement therapy. The culture of strong human tissue-engineered (TE) vascular grafts has required long culture times, up to several months, whether or not combined with gene therapy. This article describes the culture of strong, genetically unmodified, human TE vascular grafts in 4 weeks Small-diameter vascular grafts were engineered using a fast-degrading polyglycolic acid scaffold coated with poly-4-hydroxybutyrate combined with fibrin gel and seeded with myofibroblasts isolated from discarded saphenous veins from patients undergoing coronary bypass surgery. The TE grafts were subjected to dynamic strain conditions. After 28 d of in vitro culture, the grafts demonstrated burst pressures of 903 +/- 123 mmHg. Comparison with native vessels (intact human left internal mammary arteries (LIMAs) and saphenous veins) showed no significant differences in the amount of DNA, whereas the TE vessels contained approximately 50% of the native collagen content. In the physiological pressure range, up to 300 mmHg, the mechanical properties of the TE vessels were comparable to the LIMA. In this study, we showed that dynamic conditioning combined with fibrin gel cell seeding enhances the mechanical properties of small-diameter TE grafts. These grafts might provide a promising alternative to currently used vascular replacements.

Continuous flow ventricular assist devices (VADs) for mechanical circulatory support (MCS) are generally smaller and believed to be more reliable than pulsatile VADs. However, regarding continuous flow, there are concerns about the decreased pulsatility and ventricular unloading. Moreover, pulsatile VADs offer a wider range in control strategies. For this reason, we used a computer model to evaluate whether pulsatile operation of a continuous flow VAD would be more beneficial than the standard constant pump speed. The computer model describes the left and right ventricle with one-fiber heart contraction models, and the systemic, pulmonary, and coronary circulation with lumped parameter hemodynamical models, while the heart rate is regulated with a baroreflex model. With this computer model, both normal and heart failure hemodynamics were simulated. A HeartMate II left ventricular assist device model was connected to this model, and both constant speed and pulsatile support were simulated. Pulsatile support did not solve the decreased pulsatility issue, but it did improve perfusion (cardiac index and coronary flow) and unloading (stroke work and heart rate) compared with constant speed. Also, pulsatile support would be beneficial for developing control strategies, as it offers more options to adjust assist device settings to the patient's needs. Because the mathematical model used in this study can simulate different assist device settings, it can play a valuable role in developing mechanical circulatory support control strategies.