112 resultados para Pharmaceuticals formulations
Resumo:
Recent research on multiple kernel learning has lead to a number of approaches for combining kernels in regularized risk minimization. The proposed approaches include different formulations of objectives and varying regularization strategies. In this paper we present a unifying general optimization criterion for multiple kernel learning and show how existing formulations are subsumed as special cases. We also derive the criterion's dual representation, which is suitable for general smooth optimization algorithms. Finally, we evaluate multiple kernel learning in this framework analytically using a Rademacher complexity bound on the generalization error and empirically in a set of experiments.
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Psychoanalysis and related psychodynamic psychotherapies have historically had a limited engagement with substance use and antisocial personality disorders. This in part reflects an early preoccupation with ‘transference neuroses’ and in part reflects later de-emphasis of diagnosis and focus on therapeutic process. Nonetheless, psychoanalytic perspectives can usefully inform thinking about approaches to treatment of such disorders and there are psychoanalytic constructs that have specific relevance to their treatment. This paper reviews some prominent strands of psychoanalytic thinking as they pertain to the treatment of substance abuse and antisocial personality disorders. It is argued that, while Freudian formulations lead to a primarily pessimistic view of the prospect of treatment of such disorders, both the British object relations and the North American self psychology traditions suggest potentially productive approaches. Finally the limited empirical evidence from brief psychodynamically informed treatments of substance use disorders is reviewed. It is concluded that such treatments are not demonstrably effective but that, since no form of psychotherapy has established high efficacy with substance use disorders, brief psychdynamic therapies are not necessarily of lesser value than other treatments and may have specific value for particular individuals and in particular treatment contexts.
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Computer resource allocation represents a significant challenge particularly for multiprocessor systems, which consist of shared computing resources to be allocated among co-runner processes and threads. While an efficient resource allocation would result in a highly efficient and stable overall multiprocessor system and individual thread performance, ineffective poor resource allocation causes significant performance bottlenecks even for the system with high computing resources. This thesis proposes a cache aware adaptive closed loop scheduling framework as an efficient resource allocation strategy for the highly dynamic resource management problem, which requires instant estimation of highly uncertain and unpredictable resource patterns. Many different approaches to this highly dynamic resource allocation problem have been developed but neither the dynamic nature nor the time-varying and uncertain characteristics of the resource allocation problem is well considered. These approaches facilitate either static and dynamic optimization methods or advanced scheduling algorithms such as the Proportional Fair (PFair) scheduling algorithm. Some of these approaches, which consider the dynamic nature of multiprocessor systems, apply only a basic closed loop system; hence, they fail to take the time-varying and uncertainty of the system into account. Therefore, further research into the multiprocessor resource allocation is required. Our closed loop cache aware adaptive scheduling framework takes the resource availability and the resource usage patterns into account by measuring time-varying factors such as cache miss counts, stalls and instruction counts. More specifically, the cache usage pattern of the thread is identified using QR recursive least square algorithm (RLS) and cache miss count time series statistics. For the identified cache resource dynamics, our closed loop cache aware adaptive scheduling framework enforces instruction fairness for the threads. Fairness in the context of our research project is defined as a resource allocation equity, which reduces corunner thread dependence in a shared resource environment. In this way, instruction count degradation due to shared cache resource conflicts is overcome. In this respect, our closed loop cache aware adaptive scheduling framework contributes to the research field in two major and three minor aspects. The two major contributions lead to the cache aware scheduling system. The first major contribution is the development of the execution fairness algorithm, which degrades the co-runner cache impact on the thread performance. The second contribution is the development of relevant mathematical models, such as thread execution pattern and cache access pattern models, which in fact formulate the execution fairness algorithm in terms of mathematical quantities. Following the development of the cache aware scheduling system, our adaptive self-tuning control framework is constructed to add an adaptive closed loop aspect to the cache aware scheduling system. This control framework in fact consists of two main components: the parameter estimator, and the controller design module. The first minor contribution is the development of the parameter estimators; the QR Recursive Least Square(RLS) algorithm is applied into our closed loop cache aware adaptive scheduling framework to estimate highly uncertain and time-varying cache resource patterns of threads. The second minor contribution is the designing of a controller design module; the algebraic controller design algorithm, Pole Placement, is utilized to design the relevant controller, which is able to provide desired timevarying control action. The adaptive self-tuning control framework and cache aware scheduling system in fact constitute our final framework, closed loop cache aware adaptive scheduling framework. The third minor contribution is to validate this cache aware adaptive closed loop scheduling framework efficiency in overwhelming the co-runner cache dependency. The timeseries statistical counters are developed for M-Sim Multi-Core Simulator; and the theoretical findings and mathematical formulations are applied as MATLAB m-file software codes. In this way, the overall framework is tested and experiment outcomes are analyzed. According to our experiment outcomes, it is concluded that our closed loop cache aware adaptive scheduling framework successfully drives co-runner cache dependent thread instruction count to co-runner independent instruction count with an error margin up to 25% in case cache is highly utilized. In addition, thread cache access pattern is also estimated with 75% accuracy.
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The statutory demand procedure has been a part of our corporate law from its earliest modern formulations and it has been suggested, albeit anecdotally, that under the current regime, it gives rise to more litigation than any other part of the Corporations Act. Despite this there has been a lack of consideration of the underlying policy behind the procedure in both the case law and literature; both of which are largely centred on the technical aspects of the process. The purpose of this article is to examine briefly the process of the statutory demand in the context of the current insolvency law in Australia. This paper argues that robust analysis of the statutory demand regime is overdue. The paper first sets out to discover if there is a policy justification for the process and to articulate what that may be. Second, it will briefly examine the current legislation and argue that the structure actually encourages litigation which is arguably undesirable in the context of insolvency. In particular we will ask if the current rigid legal regime is appropriate for dealing efficiently with the highly charged atmosphere of contested insolvency. Third, it will examine suggested reforms in this area as to whether they might be a way forward.
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‘Wearable technology’, or the use of specialist technology in garments, is promoted by the electronics industry as the next frontier of fashion. However the story of wearable technology’s relationship with fashion begins neither with the development of miniaturised computers in the 1970s nor with sophisticated ‘smart textiles’ of the twenty-first century, despite what much of the rhetoric suggests. This study examines wearable technology against a longer history of fashion, highlighted by the influential techno-sartorial experiments of a group of early twentieth century avant-gardes including Italian Futurists Giacomo Balla and F.T. Marinetti, Russian Constructivists Varvara Stepanova and Liubov Popova, and Paris-based Cubist, Sonia Delaunay. Through the interdisciplinary framework of fashion studies, the thesis provides a fuller picture of wearable technology framed by the idea of utopia. Using comparative analysis, and applying the theoretical formulations of Fredric Jameson, Louis Marin and Michael Carter, the thesis traces the appearance of three techno-utopian themes from their origins in the machine age experiments of Balla, Marinetti, Stepanova, Popova and Delaunay to their twenty-first century reappearance in a dozen wearable technology projects. By exploring the central thesis that contemporary wearable technology resurrects the techno-utopian ideas and expressions of the early twentieth century, the study concludes that the abiding utopian impetus to embed technology in the aesthetics (prints, silhouettes, and fabrication) and functionality of fashion is to unify subject, society and environment under a totalising technological order.
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This article explores an important temporal aspect of the design of strategic alliances by focusing on the issue of time bounds specification. Time bounds specification refers to a choice on behalf of prospective alliance partners at the time of alliance formation to either pre-specify the duration of an alliance to a specific time window, or to keep the alliance open-ended (Reuer & Ariňo, 2007). For instance, Das (2006) mentions the example of the alliance between Telemundo Network and Mexican Argos Comunicacion (MAC). Announced in October 2000, this alliance entailed a joint production of 1200 hours of comedy, news, drama, reality and novella programs (Das, 2006). Conditioned on the projected date of completing the 1200 hours of programs, Telemundo Network and MAC pre-specified the time bounds of the alliance ex ante. Such time-bound alliances are said to be particularly prevalent in project-based industries, like movie production, construction, telecommunications and pharmaceuticals (Schwab & Miner, 2008). In many other instances, however, firms may choose to keep their alliances open-ended, not specifying a specific time bound at the time of alliance formation. The choice between designing open-ended alliances that are “built to last”, versus time bound alliances that are “meant to end” is important. Seminal works like Axelrod (1984), Heide & Miner (1992), and Parkhe (1993) demonstrated that the choice to place temporal bounds on a collaborative venture has important implications. More specifically, collaborations that have explicit, short term time bounds (i.e. what is termed a shorter “shadow of the future”) are more likely to experience opportunism (Axelrod, 1984), are more likely to focus on the immediate present (Bakker, Boros, Kenis & Oerlemans, 2012), and are less likely to develop trust (Parkhe, 1993) than alliances for which time bounds are kept indeterminate. These factors, in turn, have been shown to have important implications for the performance of alliances (e.g. Kale, Singh & Perlmutter, 2000). Thus, there seems to be a strong incentive for organizations to form open-ended strategic alliances. And yet, Reuer & Ariňo (2007), one of few empirical studies that details the prevalence of time-bound and open-ended strategic alliances, found that about half (47%) of the alliances in their sample were time bound, the other half were open-ended. What conditions, then, determine this choice?
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Pulmonary drug delivery is the focus of much research and development because of its great potential to produce maximum therapeutic benefit. Among the available options the dry powder inhaler (DPI) is the preferred device for the treatment of an increasingly diverse number of diseases. However, as drug delivery from a DPI involves a complicated set of physical processes and the integration of drug formulations, device design and patient usage, the engineering development of this medical technology is proving to be a great challenge. Currently there is large range of devices that are either available on the market or under development, however, none exhibit superior clinical efficacy. A major concern is the inter- and intra-patient variability of the drug dosage delivered to the deep lungs. The extent of variability depends on the drug formulation, the device design and the patient’s inhalation profile. This article reviews recent advances in DPI technology and presents the key factors which motivate and constrain the successful engineering of a universal, patient-independent DPI that is capable of efficient, reliable and repeatable drug delivery. A strong emphasis is placed on the physical processes of drug powder aerosolisation, deagglomeration, and dispersion and on the engineering of formulations and inhalers that can optimise these processes.
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Recent experience of practice-led postgraduate supervision has prompted me to conclude that the practice-led research method, as it is currently construed, produces good outcomes, especially in permitting practitioners in the creative arts, design and media into the research framework, but at the same time it also generates certain recurring difficulties. What are these difficulties? Practice-led candidates tend to rely on a narrow range of formulations with the result that they assume: (i) the innovative nature of practice-led research; (ii) that its novelty is based in opposition to other research methods; (iii) that practice is intrinsically research, often leading to tautological formulations; (iv) the hyper-self-reflexive nature of practice-led research. This set of guidelines was composed in order to circumvent the shortcomings that result from these recurring formulations. My belief is that, if these shortcomings are avoided, there is nothing to prevent practice-led from further developing as a research inquiry and thus achieving rewarding and successful research outcomes. Originally composed for the purposes of postgraduate supervision, these six rules are presented here in the context of a wider analysis of the emergence of practice-led research and its current conditions of possibility as a research method.
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Summary: The concept of using plants to produce high-value pharmaceuticals such as vaccines is 20 years old this year and is only now on the brink of realisation as an established technology. The original reliance on transgenic plants has largely given way to transient expression; proofs of concept for human and animal vaccines and of efficacy for animal vaccines have been established; several plant-produced vaccines have been through Phase I clinical trials in humans and more are scheduled; regulatory requirements are more clear than ever, and more facilities exist for manufacture of clinic-grade materials. The original concept of cheap edible vaccines has given way to a realisation that formulated products are required, which may well be injectable. The technology has proven its worth as a means of cheap, easily scalable production of materials: it now needs to find its niche in competition with established technologies. The realised achievements in the field as well as promising new developments will be reviewed, such as rapid-response vaccines for emerging viruses with pandemic potential and bioterror agents. © 2010 The Author. Journal compilation © 2010 Blackwell Publishing Ltd.
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We constructed a novel autonomously replicating gene expression shuttle vector, with the aim of developing a system for transiently expressing proteins at levels useful for commercial production of vaccines and other proteins in plants. The vector, pRIC, is based on the mild strain of the geminivirus Bean yellow dwarf virus (BeYDV-m) and is replicationally released into plant cells from a recombinant Agrobacterium tumefaciens Ti plasmid. pRIC differs from most other geminivirus-based vectors in that the BeYDV replication-associated elements were included in cis rather than from a co-transfected plasmid, while the BeYDV capsid protein (CP) and movement protein (MP) genes were replaced by an antigen encoding transgene expression cassette derived from the non-replicating A. tumefaciens vector, pTRAc. We tested vector efficacy in Nicotiana benthamiana by comparing transient cytoplasmic expression between pRIC and pTRAc constructs encoding either enhanced green fluorescent protein (EGFP) or the subunit vaccine antigens, human papillomavirus subtype 16 (HPV-16) major CP L1 and human immunodeficiency virus subtype C p24 antigen. The pRIC constructs were amplified in planta by up to two orders of magnitude by replication, while 50% more HPV-16 L1 and three- to seven-fold more EGFP and HIV-1 p24 were expressed from pRIC than from pTRAc. Vector replication was shown to be correlated with increased protein expression. We anticipate that this new high-yielding plant expression vector will contribute towards the development of a viable plant production platform for vaccine candidates and other pharmaceuticals. © 2009 Blackwell Publishing Ltd.
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This article critically analyses the role that criminological theory and specific policy formulations of culture play in the New Zealand state’s response to the over-representation of Māori in the criminal justice system. Part one provides an overview of the changing criminological explanations of, and responses to, Māori offending in New Zealand from the 1980s onwards and how these understandings extended colonialist approaches to Māori and crime into the neo-colonial context. In particular, we chart the shift in policy development from theorising Māori offending as attributable to loss of cultural identity to a focus on socio-economic and institutional antecedents and, finally, through the risk factors, assessment, and criminogenic needs approaches that have gained prominence in the current policy context. In part two, the focus moves to the strategies employed by members of the academy to elevate their own epistemological constructions of Māori social reality within the policy development process. In particular, the critique scrutinises recent attempts to portray Indigenous responses to social harm as “unscientific” and, in part, responsible for the continuing over-representation of Māori in New Zealand’s criminal justice system. The purpose of this analysis is to focus the critical, criminological gaze firmly on the activities of policy makers and administrative criminologists, to examine how their policies and approaches impact on Māori as an Indigenous people.
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Intellectual property is crucial to the promotion of innovation. It provides an incentive to innovate as well as security for investment in innovation. The industries of the 21st century-information technology, biotechnology, pharmaceuticals, communications, education and entertainment – are all knowledge-based. The WTO Agreement on Trade-Related Aspects of Intellectual Property Rights (the TRIPS Agreement), adopted in 1994 at the conclusion of the Uruguay Round of trade negotiations, requires all WTO member countries to provide for the protection and enforcement of intellectual property rights. Having forged a link for the first time between intellectual property rights and the international trading system, the adoption of TRIPS means that any country that aims to participate fully in the global economy needs to understand the role of intellectual property and align its intellectual property laws and practices with the international minimum standards prescribed by TRIPS. However, for developing and least-developed countries, the implementation of intellectual property systems and enforcement mechanisms raises questions and challenges. Does recognition and enforcement of intellectual property serve their development needs and objectives? Does TRIPS encourage or hinder the transfer of technologies to developing and least-developed countries, particularly those that meet urgent needs in areas such as public health, food security, water and energy? What is the effect of TRIPS on developing countries’ access to knowledge and information? Is there scope for flexibility in implementation of TRIPS in pursuit of development strategies?
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Hydrogels are hydrophilic, three dimensional polymers that imbibe large quantities of water while remaining insoluble in aqueous solutions due to chemical or physical cross-linking. The polymers swell in water or biological fluids, immobilizing the bioactive agent, leading to drug release in a well-defined specific manner. Thus the hydrogels’ elastic properties, swellability and biocompatibility make them excellent formulations for drug delivery. Currently, many drug potencies and therapeutic effects are limited or otherwise reduced because of the partial degradation that occurs before the administered drug reaches the desired site of action. On the other hand, sustained release medications release drugs continually, rather than providing relief of symptoms and protection solely when necessary. In fact, it would be much better if drugs could be administered in a manner that precisely matches physiological needs at desired times and at the desired site (site specific targeting). There is therefore an unmet need to develop controlled drug delivery systems especially for delivery of peptide and protein bound drugs. The purpose of this project is to produce hydrogels for structural drug delivery and time-dependent sustained release of drugs (bioactive agents). We use an innovative polymerisation strategy based on native chemical ligation (NCL) to covalently cross-link polymers to form hydrogels. When mixed in aqueous solution, four armed (polyethylene glycol) amine (PEG-4A) end functionalised with thioester and four branched Nterminal cysteine peptide dendrimers spontaneously conjugated to produce biomimetic hydrogels. These hydrogels showed superior resistance to shear stress compared to an equivalent PEG macromonomer system and were shown to be proteolytically degradable with concomitant release of a model payload molecule. This is the first report of a peptide dendrimers/PEG macromonomer approach to hydrogel production and opens up the prospect of facile hydrogel synthesis together with tailored payload release.
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Background: In response to health workforce shortages policymakers have considered expanding the roles that a health professional may perform. A more traditional combination of health professional roles is that of a dispensing doctor (DD) who routinely prescribes and dispenses pharmaceuticals. A systematic review conducted on mainly overseas DDs’ practices found that DDs tended to prescribe more items per patients, less often generically, and showed poorer adherence to best practice. Convenience for patients was cited by both patients and DDs as the main reason for dispensing. In Australia, rural doctors are allowed to dispense Pharmaceutical Benefit Scheme (PBS) subsidised pharmaceutical benefits if there is no reasonable pharmacy coverage. Little was known about the practices of these Australian DDs. Objectives: To examine the PBS prescribing patterns of dispensing with matched non-dispensing doctors and identify factors that influence prescribing behaviour. Method: A sequential explanatory (QUAN-->qual) mixed methodology was utilised. Firstly, rurality-matched DDs’ and non-DDs’ PBS data for fiscal years 2005-7 were analysed against criteria distilled from a systematic review and stakeholder consultations. Secondly, structured interviews were conducted with a purposive sample of DDs to examine the quantitative findings. Key findings: DDs prescribed significantly fewer PBS prescriptions per patients but used Regulation 24 significantly more than non-DDs. Regulation 24 biased the prescribing data. DDs prescribed proportionally more penicillin type antibiotics, adrenergic inhalants and non-steroidal anti-inflammatories as compared to non-DDs. Reasons offered by DD-respondents highlighted that prescribing was influenced by an awareness of cost to the patients, peer pressure and confidential prescriber feedback provided on a regular basis. Implications: This innovative census study does not support international data that DDs are less judicious in their prescribing. There is some evidence that DDs might reduce health inequity between rural and urban Australian, and that the DD health model is valuable to patients in isolated communities.
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Paris 1947 is the site of one of twentieth century fashion’s fictive highpoints. The New Look combined drama and poetics through an abiding rhetoric of elegance. In doing so it employed traditional modes of femininity, casting the woman of fashion in the guise of an ambiguous ‘new’ figure: half fairytale princess, half evil witch. This fashionable ideal was widely disseminated through key photographic representations, Willy Maywald’s 1947 image of the Bar Suit being a case in point. It was precisely such mythic formulations of ‘woman’ which Simone de Beauvoir was to take to task just two years later with the publication of The Second Sex. Driven by frustration with the status quo of real women, de Beauvoir recognised the role of fictive representations, both textual and visual in defining women. This paper reads key sections of The Second Sex through a comparative analysis of two iconic images of French women from 1947; Cartier-Bresson’s classic portrait of de Beauvoir and Willy Mayhold’s spectacular evocation of Christian Dior’s New Look. Cued by a compelling range of similarities between these images this paper explores links between fashion, feminism and fiction in mid-century French culture.