Continuity of care in older adults with multiple chronic conditions

Thesis (Ph.D.)--University of Washington, 2016-08

Therapeutic Potential of RNAi Through Endocytotic Methods

The ability to manipulate gene expression promises to be an important tool for the management of infectious diseases and genetic disorders. However, a major limitation to effective delivery of therapeutic RNA to living cells is the cellular toxicity of conventional techniques. Team PANACEA’s research objective was to create new reagents based on a novel small-molecule delivery system that uses a modular recombinant protein vehicle consisting of a specific ligand coupled to a Hepatitis B Virus-derived RNA binding domain (HBV-RBD). Two such recombinant delivery proteins were developed: one composed of Interleukin-8, the other consisting of the Machupo Virus GP1 protein. The ability of these proteins to deliver RNA to cells were then tested. The non-toxic nature of this technology has the potential to overcome limitations of current methods and could provide a platform for the expansion of personalized medicine.

Extensão universitária e associativismo popular : um estudo a partir da educação ambiental crítica

Partimos do pressuposto que a universidade pública é um bem do povo e deve servir aos interesses da sociedade, sobretudo aos interesses daqueles cuja vida é ameaçada mediante as condições desiguais sob as quais a sociedade capitalista se funda. Entendemos que a extensão universitária é uma atividade da universidade e deve, como ensino e pesquisa, ser reconhecida como produtora de conhecimentos e não por trabalhos assistenciais, como se caracteriza, na realidade concreta, a extensão universitária analisada nesta dissertação. Com base nisso, o trabalho que se segue discorre sobre a relação de dependência das associações populares, ligadas ao movimento da economia popular solidária à extensão da Universidade Federal do Rio Grande – FURG, especificamente aquela realizada pelo Núcleo de Desenvolvimento Social e Econômico – NUDESE-FURG, da região de Rio GrandeRS. O objetivo do trabalho foi conhecer a relação entre o núcleo e as associações, problematizando-a com base em alguns princípios da Educação Ambiental Crítica (diálogo, totalidade, relação teoria/prática e participação social). O referencial que sustenta o trabalho articula autores da sociologia do trabalho, economia da educação, ecologia política, geografia crítica, todos, de alguma forma, ligados ao materialismo histórico como perspectiva de análise. O trabalho se caracteriza como um estudo de caso, onde os principais recursos perpassaram pela análise de documentos e, fundamentalmente, as entrevistas gravadas e transcritas na íntegra, pelas quais nosso estudo se baseia. A análise do material foi feita a partir dos pressupostos da análise crítica do discurso, a qual busca entrelaçar os pronunciamentos dos sujeitos com a totalidade social na qual o discurso está inscrito, possibilitando o alcance do significado concreto. O estudo demonstra que a extensão universitária desenvolvida pelo NUDESE-FURG tem características assistencialistas, cuja consequência prática é a realização de atividades para os trabalhadores associados (principalmente elaboração e gestão de projetos), impedindo que as associações desenvolvam suas ações sem depender do núcleo. Além disso, ao assumir recursos financeiros oriundos de projetos (via editais), as associações apenas transferem para o Estado a condição de dependência do intermediário, o que não extingue o problema, mas reafirma-o. Por isso, entendemos que a Educação Ambiental Crítica oferece, por meio dos princípios que utilizamos, um instrumento crítico importante ao estudo de processos e políticas que buscam a emancipação dos sujeitos. Isso porque, também, ao reconhecer a crise socioambiental que vivemos, fruto do modo de produção capitalista, dos conflitos existentes na sociedade (portanto dos diferentes interesses, concepções e valores em disputa), pela apropriação da riqueza produzida, podem-se possibilitar conhecimentos úteis dos trabalhadores das associações. Para que isso aconteça, defendemos o encontro da extensão universitária do NUDESE-FURG com a Educação Ambiental Crítica, caso a emancipação, de fato, esteja no horizonte das práticas deste núcleo, já que pelo estudo, nesta pesquisa, predomina dependência de tais grupos do NUDESE-FURG.

Dynamic Coculture of a Prevascularized Engineered Bone Construct

The generation of functional, vascularized tissues is a key challenge for the field of tissue engineering. Before clinical implantations of tissue engineered bone constructs can succeed, in vitro fabrication needs to address limitations in large-scale tissue development, including controlled osteogenesis and an inadequate vasculature network to prevent necrosis of large constructs. The tubular perfusion system (TPS) bioreactor is an effective culturing method to augment osteogenic differentiation and maintain viability of human mesenchymal stem cell (hMSC)-seeded scaffolds while they are developed in vitro. To further enhance this process, we developed a novel osteogenic growth factors delivery system for dynamically cultured hMSCs using microparticles encapsulated in three-dimensional alginate scaffolds. In light of this increased differentiation, we characterized the endogenous cytokine distribution throughout the TPS bioreactor. An advantageous effect in the ‘outlet’ portion of the uniaxial growth chamber was discovered due to the system’s downstream circulation and the unique modular aspect of the scaffolds. This unique trait allowed us to carefully tune the differentiation behavior of specific cell populations. We applied the knowledge gained from the growth profile of the TPS bioreactor to culture a high-volume bone composite in a 3D-printed femur mold. This resulted in a tissue engineered bone construct with a volume of 200cm3, a 20-fold increase over previously reported sizes. We demonstrated high viability of the cultured cells throughout the culture period as well as early signs of osteogenic differentiation. Taking one step closer toward a viable implant and minimize tissue necrosis after implantation, we designed a composite construct by coculturing endothelial cells (ECs) and differentiating hMSCs, encouraging prevascularization and anastomosis of the graft with the host vasculature. We discovered the necessity of cell to cell proximity between the two cell types as well as preference for the natural cell binding capabilities of hydrogels like collagen. Notably, the results suggested increased osteogenic and angiogenic potential of the encapsulated cells when dynamically cultured in the TPS bioreactor, suggesting a synergistic effect between coculture and applied shear stress. This work highlights the feasibility of fabricating a high-volume, prevascularized tissue engineered bone construct for the regeneration of a critical size defect.

Preventing encrypted traffic analysis

Many existing encrypted Internet protocols leak information through packet sizes and timing. Though seemingly innocuous, prior work has shown that such leakage can be used to recover part or all of the plaintext being encrypted. The prevalence of encrypted protocols as the underpinning of such critical services as e-commerce, remote login, and anonymity networks and the increasing feasibility of attacks on these services represent a considerable risk to communications security. Existing mechanisms for preventing traffic analysis focus on re-routing and padding. These prevention techniques have considerable resource and overhead requirements. Furthermore, padding is easily detectable and, in some cases, can introduce its own vulnerabilities. To address these shortcomings, we propose embedding real traffic in synthetically generated encrypted cover traffic. Novel to our approach is our use of realistic network protocol behavior models to generate cover traffic. The observable traffic we generate also has the benefit of being indistinguishable from other real encrypted traffic further thwarting an adversary's ability to target attacks. In this dissertation, we introduce the design of a proxy system called TrafficMimic that implements realistic cover traffic tunneling and can be used alone or integrated with the Tor anonymity system. We describe the cover traffic generation process including the subtleties of implementing a secure traffic generator. We show that TrafficMimic cover traffic can fool a complex protocol classification attack with 91% of the accuracy of real traffic. TrafficMimic cover traffic is also not detected by a binary classification attack specifically designed to detect TrafficMimic. We evaluate the performance of tunneling with independent cover traffic models and find that they are comparable, and, in some cases, more efficient than generic constant-rate defenses. We then use simulation and analytic modeling to understand the performance of cover traffic tunneling more deeply. We find that we can take measurements from real or simulated traffic with no tunneling and use them to estimate parameters for an accurate analytic model of the performance impact of cover traffic tunneling. Once validated, we use this model to better understand how delay, bandwidth, tunnel slowdown, and stability affect cover traffic tunneling. Finally, we take the insights from our simulation study and develop several biasing techniques that we can use to match the cover traffic to the real traffic while simultaneously bounding external information leakage. We study these bias methods using simulation and evaluate their security using a Bayesian inference attack. We find that we can safely improve performance with biasing while preventing both traffic analysis and defense detection attacks. We then apply these biasing methods to the real TrafficMimic implementation and evaluate it on the Internet. We find that biasing can provide 3-5x improvement in bandwidth for bulk transfers and 2.5-9.5x speedup for Web browsing over tunneling without biasing.

Using a voxel-based krogh cylinder array to simulate microvascular contrast enhancement

The goal of this study is to better simulate microscopic and voxel-based dynamic contrast enhancement in magnetic resonance imaging. Specifically, errors imposed by the traditional two-compartment model are reduced by introducing a novel Krogh cylinder network. The two-compartment model was developed for macroscopic pharmacokinetic analysis of dynamic contrast enhancement and generalizing it to voxel dimensions, due to the significant decrease in scale, imposes physiologically unrealistic assumptions. In the project, a system of microscopic exchange between plasma and extravascular-extracellular space is built while numerically simulating the local contrast agent flow between and inside image elements. To do this, tissue parameter maps were created, contrast agent was introduced to the tissue via a flow lattice, and various data sets were simulated. The effects of sources, tissue heterogeneity, and the contribution of individual tissue parameters to an image are modeled. Further, the study attempts to demonstrate the effects of a priori flow maps on image contrast, indicating that flow data is as important as permeability data when analyzing tumor contrast enhancement. In addition, the simulations indicate that it may be possible to obtain tumor-type diagnostic information by acquiring both flow and permeability data.

Libtissue - Implementing Innate Immunity

In a previous paper the authors argued the case for incorporating ideas from innate immunity into artificial immune systems (AISs) and presented an outline for a conceptualframework for such systems. A number of key general properties observed in the biological innate and adaptive immune systems were highlighted, and how such properties might be instantiated in artificial systems was discussed in detail. The next logical step is to take these ideas and build a software system with which AISs with these properties can be implemented and experimentally evaluated. This paper reports on the results of that step - the libtissue system.

Dynamically managing sensed context data

This thesis reports on an investigation of the feasibility and usefulness of incorporating dynamic management facilities for managing sensed context data in a distributed contextaware mobile application. The investigation focuses on reducing the work required to integrate new sensed context streams in an existing context aware architecture. Current architectures require integration work for new streams and new contexts that are encountered. This means of operation is acceptable for current fixed architectures. However, as systems become more mobile the number of discoverable streams increases. Without the ability to discover and use these new streams the functionality of any given device will be limited to the streams that it knows how to decode. The integration of new streams requires that the sensed context data be understood by the current application. If the new source provides data of a type that an application currently requires then the new source should be connected to the application without any prior knowledge of the new source. If the type is similar and can be converted then this stream too should be appropriated by the application. Such applications are based on portable devices (phones, PDAs) for semi-autonomous services that use data from sensors connected to the devices, plus data exchanged with other such devices and remote servers. Such applications must handle input from a variety of sensors, refining the data locally and managing its communication from the device in volatile and unpredictable network conditions. The choice to focus on locally connected sensory input allows for the introduction of privacy and access controls. This local control can determine how the information is communicated to others. This investigation focuses on the evaluation of three approaches to sensor data management. The first system is characterised by its static management based on the pre-pended metadata. This was the reference system. Developed for a mobile system, the data was processed based on the attached metadata. The code that performed the processing was static. The second system was developed to move away from the static processing and introduce a greater freedom of handling for the data stream, this resulted in a heavy weight approach. The approach focused on pushing the processing of the data into a number of networked nodes rather than the monolithic design of the previous system. By creating a separate communication channel for the metadata it is possible to be more flexible with the amount and type of data transmitted. The final system pulled the benefits of the other systems together. By providing a small management class that would load a separate handler based on the incoming data, Dynamism was maximised whilst maintaining ease of code understanding. The three systems were then compared to highlight their ability to dynamically manage new sensed context. The evaluation took two approaches, the first is a quantitative analysis of the code to understand the complexity of the relative three systems. This was done by evaluating what changes to the system were involved for the new context. The second approach takes a qualitative view of the work required by the software engineer to reconfigure the systems to provide support for a new data stream. The evaluation highlights the various scenarios in which the three systems are most suited. There is always a trade-o↵ in the development of a system. The three approaches highlight this fact. The creation of a statically bound system can be quick to develop but may need to be completely re-written if the requirements move too far. Alternatively a highly dynamic system may be able to cope with new requirements but the developer time to create such a system may be greater than the creation of several simpler systems.

NFL-lipid nanocapsules for brain neural stem cell targeting in vitro and in vivo

International audience

Study of salinity gradients in the Persian Gulf and an experimental model for electric energy extraction from them using nano-membranes

Salinity gradient power (SGP) is the energy that can be obtained from the mixing entropy of two solutions with a different salt concentration. River estuary, as a place for mixing salt water and fresh water, has a huge potential of this renewable energy. In this study, this potential in the estuaries of rivers leading to the Persian Gulf and the factors affecting it are analysis and assessment. Since most of the full water rivers are in the Asia, this continent with the potential power of 338GW is a second major source of energy from the salinity gradient power in the world (Wetsus institute, 2009). Persian Gulf, with the proper salinity gradient in its river estuaries, has Particular importance for extraction of this energy. Considering the total river flow into the Persian Gulf, which is approximately equal to 3486 m3/s, the amount of theoretical extractable power from salinity gradient in this region is 5.2GW. Iran, with its numerous rivers along the coast of the Persian Gulf, has a great share of this energy source. For example, with study calculations done on data from three hydrometery stations located on the Arvand River, Khorramshahr Station with releasing 1.91M/ energy which is obtained by combining 1.26m3 river water with 0.74 m3 sea water, is devoted to itself extracting the maximum amount of extractable energy. Considering the average of annual discharge of Arvand River in Khorramshahr hydrometery station, the amount of theoretical extractable power is 955 MW. Another part of parameters that are studied in this research, are the intrusion length of salt water and its flushing time in the estuary that have a significant influence on the salinity gradient power. According to the calculation done in conditions HWS and the average discharge of rivers, the maximum of salinity intrusion length in to the estuary of the river by 41km is related to Arvand River and the lowest with 8km is for Helle River. Also the highest rate of salt water flushing time in the estuary with 9.8 days is related to the Arvand River and the lowest with 3.3 days is for Helle River. Influence of these two parameters on reduces the amount of extractable energy from salinity gradient power as well as can be seen in the estuaries of the rivers studied. For example, at the estuary of the Arvand River in the interval 8.9 days, salinity gradient power decreases 9.2%. But another part of this research focuses on the design of a suitable system for extracting electrical energy from the salinity gradient. So far, five methods have been proposed to convert this energy to electricity that among them, reverse electro-dialysis (RED) method and pressure-retarded osmosis (PRO) method have special importance in practical terms. In theory both techniques generate the same amount of energy from given volumes of sea and river water with specified salinity; in practice the RED technique seems to be more attractive for power generation using sea water and river water. Because it is less necessity of salinity gradient to PRO method. In addition to this, in RED method, it does not need to use turbine to change energy and the electricity generation is started when two solutions are mixed. In this research, the power density and the efficiency of generated energy was assessment by designing a physical method. The physical designed model is an unicellular reverse electro-dialysis battery with nano heterogenic membrane has 20cmx20cm dimension, which produced power density 0.58 W/m2 by using river water (1 g NaCl/lit) and sea water (30 g NaCl/lit) in laboratorial condition. This value was obtained because of nano method used on the membrane of this system and suitable design of the cell which led to increase the yield of the system efficiency 11% more than non nano ones.

Der Beitrag der Erziehungsberatung zur Förderung der Gesundheit von Kindern und Jugendlichen

Die Expertise für den 13. Kinder- und Jugendbericht gibt einen Überblick über Versorgungsstrukturen und Inanspruchnahme bei psychischen Störungen von Kindern und Jugendlichen. Insbesondere werden auf der Basis einer aktuellen empirischen Untersuchung „gesundheitsbezogene Anlässe“ bei der Inanspruchnahme von Erziehungsberatung beschrieben. Ein eigenes Thema bildet die ICD-10-Kategorisierbarkeit von Problemen in der Erziehungsberatung. Dabei wird der diagnostische und therapeutische Ansatz der Erziehungsberatung in Abgrenzung zur Kinder- und Jugendpsychiatrie dargestellt. Auf der Grundlage der genannten Untersuchung werden schließlich die einzelfallbezogene und die einzelfallübergreifende Zusammenarbeit der Erziehungsberatung mit dem Gesundheitswesen beschrieben. Abschließend wird die Entwicklung der Erziehungsberatung in den letzten Jahren nach Inanspruchnahme, Personal und Kosten skizziert.

Niosomes as Nanoparticular Drug Carriers: Fundamentals and Recent Applications

Drug delivery systems are defined as formulations aiming for transportation of a drug to the desired area of action within the body. The basic component of drug delivery systems is an appropriate carrier that protects the drug from rapid degradation or clearance and thereby enhances drug concentration in target tissues. Based on their biodegradable, biocompatible, and nonimmunogenic structure, niosomes are promising drug carriers that are formed by self-association of nonionic surfactants and cholesterol in an aqueous phase. In recent years, numerous research articles have been published in scientific journals reporting the potential of niosomes to serve as a carrier for the delivery of different types of drugs. The present review describes preparation methods, characterization techniques, and recent studies on niosomal drug delivery systems and also gives up to date information regarding recent applications of niosomes in drug delivery.

Advanced parametrical modelling of 24 GHz radar sensor IC packaging components

This paper deals with the development of an advanced parametrical modelling concept for packaging components of a 24 GHz radar sensor IC used in automotive driver assistance systems. For fast and efficient design of packages for system-in-package modules (SiP), a simplified model for the description of parasitic electromagnetic effects within the package is desirable, as 3-D field computation becomes inefficient due to the high density of conductive elements of the various signal paths in the package. By using lumped element models for the characterization of the conductive components, a fast indication of the design's signal-quality can be gained, but so far does not offer enough flexibility to cover the whole range of geometric arrangements of signal paths in a contemporary package. This work pursues to meet the challenge of developing a flexible and fast package modelling concept by defining parametric lumped-element models for all basic signal path components, e.g. bond wires, vias, strip lines, bumps and balls. © Author(s) 2011. CC Attribution 3.0 License.

Development of nanostructured hydrogel for spatial and temporal controlled release of active compounds

L’utilisation de nanovecteurs pour la livraison contrôlée de principes actifs est un concept commun de nous jours. Les systèmes de livraison actuels présentent encore cependant des limites au niveau du taux de relargage des principes actifs ainsi que de la stabilité des transporteurs. Les systèmes composés à la fois de nanovecteurs (liposomes, microgels et nanogels) et d’hydrogels peuvent cependant permettre de résoudre ces problèmes. Dans cette étude, nous avons développé un système de livraison contrôlé se basant sur l’incorporation d’un nanovecteur dans une matrice hydrogel dans le but de combler les lacunes des systèmes se basant sur un vecteur uniquement. Une telle combinaison pourrait permettre un contrôle accru du relargage par stabilisation réciproque. Plus spécifiquement, nous avons développé un hydrogel structuré intégrant des liposomes, microgels et nanogels séparément chargés en principes actifs modèles potentiellement relargués de manière contrôlé. Ce contrôle a été obtenu par la modification de différents paramètres tels que la température ainsi que la composition et la concentration en nanovecteurs. Nous avons comparé la capacité de chargement et la cinétique de relargage de la sulforhodamine B et de la rhodamine 6G en utilisant des liposomes de DOPC et DPPC à différents ratios, des nanogels de chitosan/acide hyaluronique et des microgels de N-isopropylacrylamide (NIPAM) à différents ratios d’acide méthacrylique, incorporés dans un hydrogel modèle d’acrylamide. Les liposomes présentaient des capacités de chargement modérés avec un relargage prolongé sur plus de dix jours alors que les nanogels présentaient des capacités de chargement plus élevées mais une cinétique de relargage plus rapide avec un épuisement de la cargaison en deux jours. Comparativement, les microgels relarguaient complétement leur contenu en un jour. Malgré une cinétique de relargage plus rapide, les microgels ont démontré la possibilité de contrôler finement le chargement en principe actif. Ce contrôle peut être atteint par la modification des propriétés structurelles ou en changeant le milieu d’incubation, comme l’a montré la corrélation avec les isothermes de Langmuir. Chaque système développé a démontré un potentiel contrôle du taux de relargage, ce qui en fait des candidats pour des investigations futures.

Serviço de Apoio à Inclusão em eLearning (SAIeL) : educação para todos : contributo para a inclusão de cidadãos com necessidades educativas especiais no ensino superior a distância em regime de elearning

A proposta de um Serviço de Apoio à Inclusão em eLearning (SAIeL) surge da necessidade de promover o eLearning como uma ferramenta importante para que os cidadãos com Necessidades Educativas Especiais possam aceder e ter sucesso no Ensino Superior. O trabalho desenvolveu-se em torno da seguinte pergunta de partida: Cumprindo o seu papel social de Educação para Todos, de que forma podem as instituições de ensino superior facilitar ativamente o acesso e o sucesso de cidadãos com Necessidades Educativas Especiais que desejem estudar em regime de eLearning? Constituindo o ensino a distância de nova geração, uma opção com características bastante vantajosas para os cidadãos com Necessidades Educativas Especiais, pretende-se também atrair mais cidadãos para esta modalidade de educação, através da oferta e divulgação de condições mais apelativas e que encorajem as pessoas com Necessidades Educativas Especiais a prosseguir os seus estudos ao nível superior, reduzindo as barreiras e promovendo os fatores de inclusão. Procurou-se delinear um projeto de serviço que possa responder às necessidades identificadas a partir de um conjunto de fatores: i) da investigação sobre a resposta a esta problemática por parte dum conjunto de universidades de Ensino a Distância, ii) das boas práticas já existentes em instituições de ensino superior portuguesas e iii) do estudo das perceções recolhidas junto dos vários intervenientes: estudantes, professores e cidadãos com NEE. Neste quadro, foram definidas 3 fases para a elaboração do trabalho: (1) auscultação dos intervenientes e levantamento de necessidades; (2) enquadramento do projeto de serviço na orgânica das instituições de ensino superior a distância e (3) organização e estruturação de um projeto de serviço através da elaboração de um Regimento, no qual são estipulados os seus objetivos, valências, competências e forma de avaliação, de maneira a dar resposta às necessidades identificadas previamente e a prevenir situações futuras.