826 resultados para Transdermal Delivery
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A novelty approach to self-assembling stereocomplex micelles by enantiomeric PLA-PEG block copolymers as a drug delivery carrier was described. The particles were encapsulated by enantiomeric PLA-PEG stereocomplex to form nanoscale micelles different from the microspheres or the single micelles by PLLA or PDLA in the reported literatures. First, the block copolymers of enantiomeric poly(L-lactide)-poly(ethylene-glycol) (PLLA-PEG) and poly(D-lactide)-poly(ethylene-glycol) (PDLA-PEG) were synthesized by the ring-opening polymerization of L-lactide and D-lactide in the presence of monomethoxy PEG, respectively. Second, the stereocomplex block copolymer micelles were obtained by the self-assembly of the equimolar mixtures of enantiomeric PLA-PEG copolymers in water. These micelles possessed partially the crystallized hydrophobic cores with the critical micelle concentrations (cmc) in the range of 0.8-4.8 mg/l and the mean hydrodynamic diameters ranging from 40 to 120 nm. The micelle sizes and cmc values obviously depended on the hydrophobic block PLA content in the copolymer.Compared with the single PLLA-PEG or PDLA PEG micelles, the cmc values of the stereocomplex micelles became lower and the sizes of the stereocomplex micelles formed smaller. And lastly, the stereocomplex micelles encapsulated with rifampin were tested for the controlled release application.
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The influences of surfactants and medical drugs on the diameter size and uniformity of electrospun poly(L-lactic acid) (PLLA) fibers were examined by adding various surfactants (cationic, anionic, and nonionic) and typical drugs into the PLLA solution. Significant diameter reduction and uniformity improvement were observed. It was shown that the drugs were capsulated inside of the fibers and the drug release in the presence of proteinase K followed nearly zero-order kinetics due to the degradation of the PLLA fibers. Such ultrafine fiber mats containing drugs may find clinical applications in the future.
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This paper explores the organisational experiences of governmental policy change and implementation on the third sector. Using a four-year longitudinal study of 13 third sector organisations (TSOs) it provides evidence based on the experiences of, and effects on, third sector organisations involved in the UK’s Work Programme in Scotland. The paper explores third sector experiences of the Work Programme during the preparation and introductory phase, as well as the effects of subsequent Work Programme implementation. By gathering evidence contemporaneously and longitudinally a unique in-depth analysis is provided of the introduction and implementation of a major new policy. The resource cost and challenges to third sector ways of working for the organisations in the Work Programme supply chain, as well as those not in the supply chain, are considered. The paper considers some of the responses adopted by the third sector to manage the opportunities and challenges presented to them through the implementation of the Work Programme. The paper also reflects on the broader context of the employability services landscape and raises questions as to whether, as a result of the manner in which the Work Programme was contracted, there is evidence of a move towards service homogenisation, challenging perceived TSO characteristics of service innovation and personalisation.
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Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas
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Background: The loss of working-aged adults to HIV/AIDS has been shown to increase the costs of labor to the private sector in Africa. There is little corresponding evidence for the public sector. This study evaluated the impact of AIDS on the capacity of a government agency, the Zambia Wildlife Authority (ZAWA), to patrol Zambia’s national parks. Methods: Data were collected from ZAWA on workforce characteristics, recent mortality, costs, and the number of days spent on patrol between 2003 and 2005 by a sample of 76 current patrol officers (reference subjects) and 11 patrol officers who died of AIDS or suspected AIDS (index subjects). An estimate was made of the impact of AIDS on service delivery capacity and labor costs and the potential net benefits of providing treatment. Results: Reference subjects spent an average of 197.4 days on patrol per year. After adjusting for age, years of service, and worksite, index subjects spent 62.8 days on patrol in their last year of service (68% decrease, p<0.0001), 96.8 days on patrol in their second to last year of service (51% decrease, p<0.0001), and 123.7 days on patrol in their third to last year of service (37% decrease, p<0.0001). For each employee who died, ZAWA lost an additional 111 person-days for management, funeral attendance, vacancy, and recruitment and training of a replacement, resulting in a total productivity loss per death of 2.0 person-years. Each AIDS-related death also imposed budgetary costs for care, benefits, recruitment, and training equivalent to 3.3 years’ annual compensation. In 2005, AIDS reduced service delivery capacity by 6.2% and increased labor costs by 9.7%. If antiretroviral therapy could be provided for $500/patient/year, net savings to ZAWA would approach $285,000/year. Conclusion: AIDS is constraining ZAWA’s ability to protect Zambia’s wildlife and parks. Impacts on this government agency are substantially larger than have been observed in the private sector. Provision of ART would result in net budgetary savings to ZAWA and greatly increase its service delivery capacity.
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Internet streaming applications are adversely affected by network conditions such as high packet loss rates and long delays. This paper aims at mitigating such effects by leveraging the availability of client-side caching proxies. We present a novel caching architecture (and associated cache management algorithms) that turn edge caches into accelerators of streaming media delivery. A salient feature of our caching algorithms is that they allow partial caching of streaming media objects and joint delivery of content from caches and origin servers. The caching algorithms we propose are both network-aware and stream-aware; they take into account the popularity of streaming media objects, their bit-rate requirements, and the available bandwidth between clients and servers. Using realistic models of Internet bandwidth (derived from proxy cache logs and measured over real Internet paths), we have conducted extensive simulations to evaluate the performance of various cache management alternatives. Our experiments demonstrate that network-aware caching algorithms can significantly reduce service delay and improve overall stream quality. Also, our experiments show that partial caching is particularly effective when bandwidth variability is not very high.
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To serve asynchronous requests using multicast, two categories of techniques, stream merging and periodic broadcasting have been proposed. For sequential streaming access where requests are uninterrupted from the beginning to the end of an object, these techniques are highly scalable: the required server bandwidth for stream merging grows logarithmically as request arrival rate, and the required server bandwidth for periodic broadcasting varies logarithmically as the inverse of start-up delay. However, sequential access is inappropriate to model partial requests and client interactivity observed in various streaming access workloads. This paper analytically and experimentally studies the scalability of multicast delivery under a non-sequential access model where requests start at random points in the object. We show that the required server bandwidth for any protocols providing immediate service grows at least as the square root of request arrival rate, and the required server bandwidth for any protocols providing delayed service grows linearly with the inverse of start-up delay. We also investigate the impact of limited client receiving bandwidth on scalability. We optimize practical protocols which provide immediate service to non-sequential requests. The protocols utilize limited client receiving bandwidth, and they are near-optimal in that the required server bandwidth is very close to its lower bound.
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Overlay networks have emerged as a powerful and highly flexible method for delivering content. We study how to optimize throughput of large, multipoint transfers across richly connected overlay networks, focusing on the question of what to put in each transmitted packet. We first make the case for transmitting encoded content in this scenario, arguing for the digital fountain approach which enables end-hosts to efficiently restitute the original content of size n from a subset of any n symbols from a large universe of encoded symbols. Such an approach affords reliability and a substantial degree of application-level flexibility, as it seamlessly tolerates packet loss, connection migration, and parallel transfers. However, since the sets of symbols acquired by peers are likely to overlap substantially, care must be taken to enable them to collaborate effectively. We provide a collection of useful algorithmic tools for efficient estimation, summarization, and approximate reconciliation of sets of symbols between pairs of collaborating peers, all of which keep messaging complexity and computation to a minimum. Through simulations and experiments on a prototype implementation, we demonstrate the performance benefits of our informed content delivery mechanisms and how they complement existing overlay network architectures.
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We consider the problem of delivering popular streaming media to a large number of asynchronous clients. We propose and evaluate a cache-and-relay end-system multicast approach, whereby a client joining a multicast session caches the stream, and if needed, relays that stream to neighboring clients which may join the multicast session at some later time. This cache-and-relay approach is fully distributed, scalable, and efficient in terms of network link cost. In this paper we analytically derive bounds on the network link cost of our cache-and-relay approach, and we evaluate its performance under assumptions of limited client bandwidth and limited client cache capacity. When client bandwidth is limited, we show that although finding an optimal solution is NP-hard, a simple greedy algorithm performs surprisingly well in that it incurs network link costs that are very close to a theoretical lower bound. When client cache capacity is limited, we show that our cache-and-relay approach can still significantly reduce network link cost. We have evaluated our cache-and-relay approach using simulations over large, synthetic random networks, power-law degree networks, and small-world networks, as well as over large real router-level Internet maps.
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The advent of virtualization and cloud computing technologies necessitates the development of effective mechanisms for the estimation and reservation of resources needed by content providers to deliver large numbers of video-on-demand (VOD) streams through the cloud. Unfortunately, capacity planning for the QoS-constrained delivery of a large number of VOD streams is inherently difficult as VBR encoding schemes exhibit significant bandwidth variability. In this paper, we present a novel resource management scheme to make such allocation decisions using a mixture of per-stream reservations and an aggregate reservation, shared across all streams to accommodate peak demands. The shared reservation provides capacity slack that enables statistical multiplexing of peak rates, while assuring analytically bounded frame-drop probabilities, which can be adjusted by trading off buffer space (and consequently delay) and bandwidth. Our two-tiered bandwidth allocation scheme enables the delivery of any set of streams with less bandwidth (or equivalently with higher link utilization) than state-of-the-art deterministic smoothing approaches. The algorithm underlying our proposed frame-work uses three per-stream parameters and is linear in the number of servers, making it particularly well suited for use in an on-line setting. We present results from extensive trace-driven simulations, which confirm the efficiency of our scheme especially for small buffer sizes and delay bounds, and which underscore the significant realizable bandwidth savings, typically yielding losses that are an order of magnitude or more below our analytically derived bounds.
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We propose a new technique for efficiently delivering popular content from information repositories with bounded file caches. Our strategy relies on the use of fast erasure codes (a.k.a. forward error correcting codes) to generate encodings of popular files, of which only a small sliding window is cached at any time instant, even to satisfy an unbounded number of asynchronous requests for the file. Our approach capitalizes on concurrency to maximize sharing of state across different request threads while minimizing cache memory utilization. Additional reduction in resource requirements arises from providing for a lightweight version of the network stack. In this paper, we describe the design and implementation of our Cyclone server as a Linux kernel subsystem.
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Science Foundation Ireland (CSET - Centre for Science, Engineering and Technology, Grant No. 07/CE/11147)