932 resultados para delivery model


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ABSTRACT The higher education systems throughout the continent of Africa are undergoing unprecedented challenges and are considered in crisis. African countries, including Ghana, all have in common ties to their colonial legacy whereby they are confronted with weak policies put in place by their colonizers. Having gained their independence, Africans should now take responsibility for the task of reforming their higher education system. To date, nothing substantial has been accomplished, with serious implications for weakening and damaging the structures of the foundation of their educational systems. This qualitative, single case study utilized a postcolonial theory-critical pedagogy framework, providing guidance for coming to grips with the mindset posed by Ghana's colonial heritage in the postcolonial era, especially in terms of its damaging effects on Ghana's higher education system. The study explores alternative pathways for secondary school students to transition to tertiary education--a problematic transition that currently hinders open access to all and equality in educational opportunity, resulting in a tremendous pool of discontinued students. This transitional problem is directly related to Ghana's crisis in higher education with far reaching consequences. The alternative pathway considered in this study is an adaptation of the U.S. community college model or an integration of its applicable aspects into the current structures of the higher education system already in place. In-depth interviews were conducted with 5 Ghanaian professors teaching at community colleges in the United States, 5 Ghanaian professors teaching at universities in Ghana, and 2 educational consultants from the Ghanaian Ministry of Education. Based on their perspectives of the current state of Ghanaian higher education, analyzed in terms of pedagogy, structure/infrastructure, and curriculum, the participants provided their perceptions of salient aspects of the U.S. community college model that would be applicable to Ghana's situation, along with other recommendations. Access to all, including equality of educational opportunity, was considered essential, followed by adaptability, affordability, practicality, and quality of curriculum content and delivery. Canada's successful adaptation of the U.S. model was also discussed. Findings can help guide consideration of alternative pathways to higher education in Ghana and Africa as a whole.

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Terrigenous sediment supply, marine transport, and depositional processes along tectonically active margins are key to decoding turbidite successions as potential archives of climatic and seismic forcings. Sequence stratigraphic models predict coarse-grained sediment delivery to deep-marine sites mainly during sea-level fall and lowstand. Marine siliciclastic deposition during transgressions and highstands has been attributed to sustained connectivity between terrigenous sources and marine sinks facilitated by narrow shelves. To decipher the controls on Holocene highstand turbidite deposition, we analyzed 12 sediment cores from spatially discrete, coeval turbidite systems along the Chile margin (29° - 40°S) with changing climatic and geomorphic characteristics but uniform changes in sea level. Sediment cores from intraslope basins in north-central Chile (29° - 33°S) offshore a narrow to absent shelf record a shut-off of turbidite deposition during the Holocene due to postglacial aridification. In contrast, core sites in south-central Chile (36° - 40°S) offshore a wide shelf record frequent turbidite deposition during highstand conditions. Two core sites are linked to the Biobío river-canyon system and receive sediment directly from the river mouth. However, intraslope basins are not connected via canyons to fluvial systems but yield even higher turbidite frequencies. High sediment supply combined with a wide shelf and an undercurrent moving sediment toward the shelf edge appear to control Holocene turbidite sedimentation and distribution. Shelf undercurrents may play an important role in lateral sediment transport and supply to the deep sea and need to be accounted for in sediment-mass balances.

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Thesis (Ph.D.)--University of Washington, 2016-06

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This study demonstrates the effectiveness of a novel self-adjuvanting vaccine delivery system for multiple different synthetic peptide immunogens by use of lipid core peptide (LCP) technology. An LCP formulation incorporating two different protective epitopes of the surface antiphagocytic M protein of group A streptococci (GAS)-the causative agents of rheumatic fever and subsequent rheumatic heart disease-was tested in a murine parenteral immunization and GAS challenge model. Mice were immunized with the LCP-GAS formulation, which contains an M protein amino-terminal type-specific peptide sequence (8830) in combination with a conserved non-host-cross-reactive carboxy-terminal C-region peptide sequence (J8) of the M protein. Our data demonstrated immunogenicity of the LCP-8830-J8 formulation in B10.BR mice when coadministered in complete Freund's adjuvant and in the absence of a conventional adjuvant. In both cases, immunization led to induction of high-titer GAS peptide-specific serum immunoglobulin G antibody responses and induction of highly opsonic antibodies that did not cross-react with human heart tissue proteins. Moreover, mice were completely protected from GAS infection when immunized with LCP-8830-J8 in the presence or absence of a conventional adjuvant. Mice were not protected, however, following immunization with an LCP formulation containing a control peptide from a Schistosoma sp. These data support the potential of LCP technology in the development of novel self-adjuvanting multi-antigen component vaccines and point to the potential application of this system in the development of human vaccines against infectious diseases.

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A model was developed in dogs to determine the impact of oral enrofloxacin administration on the indigenous coliform population in the gastrointestinal tract and subsequent disposition to colonization by a strain of multidrug-resistant Escherichia coli (MDREC). Dogs given a daily oral dose of 5 mg enrofloxacin kg(-1) for 21 consecutive days showed a significant decline in faecal coliforms to levels below detectable limits by 72 In of administration. Subsequently, faecal coliforms remained suppressed throughout the period of enrofloxacin dosing. Upon termination of antibiotic administration, the number of excreted faecal coliforms slowly returned over an 8-day period, to levels comparable to those seen prior to antibiotic treatment. Enrofloxacin-treated dogs were more effectively colonized by MDREC, evidenced by a significantly increased count of MDREC in the faeces (7.1 +/- 1.5 log(10) g(-1)) compared with non-antibiotic-treated dogs (5.2 +/- 1.2; P = 0.003). Furthermore, antibiotic treatment also sustained a significantly longer period of MDREC excretion in the faeces (26.8 +/- 10.5 days) compared with animals not treated with enrofloxacin (8.5 +/- 5.4 days; P = 0.0215). These results confirm the importance of sustained delivery of an antimicrobial agent to maintain and expand the colonization potential of drug-resistant bacteria in vivo, achieved in part by reducing the competing commensal coliforms in the gastrointestinal tract to below detectable levels in the faeces. Without in vivo antimicrobial selection pressure, commensal coliforms dominated the gastrointestinal tract at the expense of the MDREC population. Conceivably, the model developed could be used to test the efficacy of novel non-antibiotic strategies aimed at monitoring and controlling gastrointestinal colonization by multidrug-resistant members of the Enterobacteriaceae that cause nosocomial infections.

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This study investigates a stent-less local delivery system for anti-restenotic agents utilizing antibodies to cross-linked fibrin (XLF). Heparin and low molecular weight heparin (LMWH) were conjugated to an antibody to cross-linked fibrin D-dinner (1D2). Rabbit right carotid arteries were injured with a balloon catheter, then the animals were given a bolus injection of 40 mug/k,g 1D2-heparin (26-70 mug/kg heparin) or 1D2-LMWH (29-80 mug/kg LMWH) conjugates or controls of saline (0.5 ml/kg), heparin (150 U/kg), LMWH (2 mg), or 1D2 (40 mug/kg), with or without a heparin bolus and sacrificed after 2 weeks (8 groups, n = 6/group). The injured artery of rabbits given 1D2-heparin or 1D2-LMWH conjugates had reduced neointimal development, with decreased luminal narrowing and positive remodelling compared with animals given control drugs. Animals given 1D2-heparin conjugate (with a heparin bolus) had three to five times more endothelial cells than the rabbits given saline or unconjugated heparin, while rabbits given 1D2-LMWH conjugate had up to 59% fewer neointimal cells than those given unconjugated drugs. There was little difference in extracellular matrix organization or composition. Thus cross-linked fibrin-antibodies can site-deliver anti-restenotic agents to injured areas of the artery wall where they influence wall remodelling and endothelial and neointimal cell number, reducing neointimal formation without systemic complications. Local delivery of anti-restenotic agents should minimise systemic effects, bleeding complications and potentially the cost of treatment due to a single, lower dose. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

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Ocular neovascularisation is the leading cause of blindness in developed countries and the most potent angiogenic factor associated with neovascularisation is vascular endothelial growth factor (VEGF). We have previously described a sense oligonucleotide (ODN-1) that possesses anti-human and rat VEGF activity. This paper describes the synthesis of lipid-lysine dendrimers and their subsequent ability to delivery ODN-1 to its target and mediate a reduction in VEGF concentration both in vitro and in vivo. Positively charged dendrimers were used to deliver ODN-1 into the nucleus of cultured D407 cells. The effects on VEGF mRNA transcription and protein expression were analysed using RT-PCR and ELISA, respectively. The most effective dendrimers in vitro were further investigated in vivo using an animal model of choroidal neovascularisation (CNV). All dendrimer/ODN-1 complexes mediated in a significant reduction in VEGF expression during an initial 24 hr period (40-60%). Several complexes maintained this level of VEGF reduction during a subsequent, second 24 hr period, which indicated protection of ODN-1 from the effects of endogenous nucleases. In addition, the transfection efficiency of dendrimers that possessed 8 positive charges (chi = 81(.)51%) was significantly better (P = 0(.)0036) than those that possessed 4 positive charges (chi = 56(.)8%). RT-PCR revealed a correlation between levels of VEGF protein mRNA. These results indicated that the most effective structural combination was three branched chains of intermediate length with 8 positive charges such as that found for dendrimer 4. Dendrimer 4 and 7/ODN-1 complexes were subsequently chosen for in vivo analysis. Fluorescein angiography demonstrated that both dendrimers significantly (P < 0(.)0001) reduced the severity of laser mediated CNV for up to two months post-injection. This study demonstrated that lipophilic, charged dendrimer mediated delivery of ODN-1 resulted in the down-regulation of in vitro VEGF expression. In addition, in vivo delivery of ODN-1 by two of the dendrimers resulted in significant inhibition of CNV in an inducible rat model. Time course studies showed that the dendrimer/ODN-1 complexes remained active for up to two months indicating the dendrimer compounds provided protection against the effects of nucleases. (C) 2004 Elsevier Ltd. All rights reserved.

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This paper proposes a theoretical explanation of the variations of the sediment delivery ratio (SDR) versus catchment area relationships and the complex patterns in the behavior of sediment transfer processes at catchment scale. Taking into account the effects of erosion source types, deposition, and hydrological controls, we propose a simple conceptual model that consists of two linear stores arranged in series: a hillslope store that addresses transport to the nearest streams and a channel store that addresses sediment routing in the channel network. The model identifies four dimensionless scaling factors, which enable us to analyze a variety of effects on SDR estimation, including (1) interacting processes of erosion sources and deposition, (2) different temporal averaging windows, and (3) catchment runoff response. We show that the interactions between storm duration and hillslope/channel travel times are the major controls of peak-value-based sediment delivery and its spatial variations. The interplay between depositional timescales and the travel/residence times determines the spatial variations of total-volume-based SDR. In practical terms this parsimonious, minimal complexity model could provide a sound physical basis for diagnosing catchment to catchment variability of sediment transport if the proposed scaling factors can be quantified using climatic and catchment properties.

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A model drug release study on the ingress of water and Kokubo simulated body fluid (SBF) into poly(2-hydroxyethyl methacrylate) (THFMA) and its copolymers with tetrahydrofurfuryl methacrylate (THFMA) loaded with vitamin B-12 was undertaken over the temperature range 298-318 K. The polymers were studied as cylinders and were loaded with either 5 or 10 wt-% of the drug. The drug release from the polymers was found to follow a Fickian diffusion mechanism in the early stages of the drug release, with higher normalized release rates at higher temperatures and higher drug loadings. The normalized release rates were also found to be higher for the SBF solution than for water. The copolymer composition was found to have a significant effect on the rate of release of the drug, with the rate falling rapidly between HEMA mole fractions of 1.0 and 0.8, but for lower mole fractions of HEMA the normalized release rate decreased more slowly. This behaviour followed the trend found for the changes in the equilibrium penetrant contents for the copolymers.

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A mobile interactive online health system was used to conduct virtual ward rounds at a regional hospital which had no specialist paediatrician. The system was wireless, which allowed telepaediatric services to be delivered direct to the bedside. Between December 2004 and May 2005, 43 virtual ward rounds were coordinated between specialists based in Brisbane and local staff at the Gladstone Hospital. Eighty-six consultations were provided for 64 patients. The most common conditions included asthma (27%), chest infections (12%), gastroenteritis (10%) and urinary tract infections (10%). In the majority of cases, there were partial (67%) or complete changes (11%) in the clinical management of patients. Specialist services were offered by a team of 13 clinicians at the Royal Children's Hospital: 10 general paediatricians, two physiotherapists and one registered nurse. Feedback from all consultants involved in the service and local staff in Gladstone was extremely positive. In 43 videoconference calls there were three technical problems, probably due to an intermittent mains power supply at the regional hospital. There appears to be potential for other rural and regional hospitals to adopt this model of service delivery.

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Water-in-oil microemulsions (w/o ME) capable of undergoing a phase-transition to lamellar liquid crystals (LC) or bicontinuous ME upon aqueous dilution were formulated using Crodarnol EO, Crill 1 and Crillet 4, an alkanol or alkanediol as cosurfactant and water. The hypothesis that phase-transition of ME to LC may be induced by tears and serve to prolong precomeal retention was tested. The ocular irritation potential of components and formulations was assessed using a modified hen's egg chorioallantoic membrane test (HET-CAM) and the preocular retention of selected formulations was investigated in rabbit eye using gamma scintigraphy. Results showed that Crill 1, Crillet 4 and Crodamol EO were non-irritant. However, all other cosurfactants investigated were irritant and their irritation was dependent on their carbon chain length. A w/o ME formulated without cosurfactant showed a protective effect when a strong irritant (0.1 M NaOH) was used as the aqueous phase. Precorneal clearance studies revealed that the retention of colloidal and coarse dispersed systems was significantly greater than an aqueous solution with no significant difference between ME systems (containing 5% and 10% water) as well as o/w emulsion containing 85% water. Conversely, a LC system formulated without cosurfactant displayed a significantly greater retention compared to other formulations. (c) 2005 Elsevier B.V. All rights reserved.

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A comparison of a constant (continuous delivery of 4% FiO(2)) and a variable (initial 5% FiO(2) with adjustments to induce low amplitude EEG (LAEEG) and hypotension) hypoxic/ischemic insult was performed to determine which insult was more effective in producing a consistent degree of survivable neuropathological damage in a newborn piglet model of perinatal asphyxia. We also examined which physiological responses contributed to this outcome. Thirty-nine 1-day-old piglets were subjected to either a constant hypoxic/ischemic insult of 30- to 37-min duration or a variable hypoxic/ischemic insult of 30-min low peak amplitude EEG (LAEEG < 5 mu V) including 10 min of low mean arterial blood pressure (MABP < 70% of baseline). Control animals (n = 6) received 21% FiO(2) for the duration of the experiment. At 72 h, the piglets were euthanased, their brains removed and fixed in 4% paraformaldehyde and assessed for hypoxic/ischemic injury by histological analysis. Based on neuropathology scores, piglets were grouped as undamaged or damaged; piglets that did not survive to 72 h were grouped separately as dead. The variable insult resulted in a greater number of piglets with neuropathological damage (undamaged = 12.5%, damaged = 68.75%, dead = 18.75%) while the constant insult resulted in a large proportion of undamaged piglets (undamaged = 50%, damaged = 22.2%, dead = 27.8%). A hypoxic insult varied to maintain peak amplitude EEG < 5 mu V results in a greater number of survivors with a consistent degree of neuropathological damage than a constant hypoxic insult. Physiological variables MABP, LAEEG, pH and arterial base excess were found to be significantly associated with neuropathological outcome. (c) 2006 Elsevier B.V. All rights reserved.

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Aim: The aim of this report was to assess the strength and influence of periodontitis as a possible risk factor for pre-term birth (PTB) in a cohort of 81 primiparous Croatian mothers aged 18-39 years. Methods: PTB cases (n=17; mean age 25 +/- 2.9 years; age range 20-33 years) were defined as spontaneous delivery after less than 37 completed weeks of gestation that were followed by spontaneous labour or spontaneous rupture of membranes. Controls (full-time births) were normal births at or after 37 weeks of gestation (n=64; mean age 25 +/- 2.9 years; age range 19-39 years). Information on known risk factors and obstetric factors included the current pregnancy history, maternal age at delivery, pre-natal care, nutritional status, tobacco use, alcohol use, genitourinary infections, vaginosis, gestational age, and birth weight. Full-mouth periodontal examination was performed on all mothers within 2 days of delivery. Results: PTB cases had significantly worse periodontal status than controls (p=0.008). Multivariate logistic regression model, after controlling for other risk factors, demonstrated that periodontal disease is a significant independent risk factor for PTB, with an adjusted odds ratio of 8.13 for the PTB group (95% confidence interval 2.73-45.9). Conclusion: Periodontal disease represents a strong, independent, and clinically significant risk factor for PTB in the studied cohort. There are strong indicators that periodontal therapy should form a part of preventive prenatal care in Croatia.

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Background: Biolistic injections provide a needle-free delivery of antigen-laden microparticles to the epithelium. The precision of the injection preferentially targets the Langerhans cell network, which, although ideal for vaccination, might not be suitable for the downregulation of immune responses in immunotherapy. Objective: We sought to determine the ability of biolistic injection of antigen into the epithelium of sensitized mice to inhibit IgE antibody and lung inflammatory responses produced by further exposure to antigen. Methods: Mice were sensitized by means of a needle injection of ovalbumin (OVA) in alum and given a series of biolistic injections of OVA or vehicle control, followed by a boost of OVA in alum. Serum IgE and IgG antibodies were measured before and after the boost. The mice were then challenged intranasally, and the infiltration of inflammatory cells was measured by means of bronchoalveolar lavage. Airway reactivity of the challenged mice was measured by examining responses to methacholine with forced oscillatory techniques. Results: Biolistic injection of OVA into the dorsal skin of sensitized mice markedly inhibited IgE and IgG1 antibody responses induced by boosting. IgG2a antibody responses were reduced rather than stimulated. The eosinophilic inflammation in the bronchoalveolar lavage fluid induced by intranasal challenge was also markedly inhibited. Lung hyperreactivity showed an initial increase and then a decrease of responsiveness to methacholine, with elastance returning to the level of unsensitized mice. Biolistic injection into the buccal epithelium was also inhibitory. Conclusions: Biolistic injection of allergen inhibited the boosting of IgE antibody and eosinophilic lung inflammatory responses without inducing TO immunity.

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This paper presents a scientific and technical description of the modelling framework and the main results of modelling the long-term average sediment delivery at hillslope to medium-scale catchments over the entire Murray Darling Basin (MDB). A theoretical development that relates long-term averaged sediment delivery to the statistics of rainfall and catchment parameters is presented. The derived flood frequency approach was adapted to investigate the problem of regionalization of the sediment delivery ratio (SDR) across the Basin. SDR, a measure of catchment response to the upland erosion rate, was modeled by two lumped linear stores arranged in series: hillslope transport to the nearest streams and flow routing in the channel network. The theory shows that the ratio of catchment sediment residence time (SRT) to average effective rainfall duration is the most important control in the sediment delivery processes. In this study, catchment SRTs were estimated using travel time for overland flow multiplied by an enlargement factor which is a function of particle size. Rainfall intensity and effective duration statistics were regionalized by using long-term measurements from 195 pluviograph sites within and around the Basin. Finally, the model was implemented across the MDB by using spatially distributed soil, vegetation, topographical and land use properties under Geographic Information System (GIs) environment. The results predict strong variations in SDR from close to 0 in floodplains to 70% in the eastern uplands of the Basin. (c) 2005 Elsevier Ltd. All rights reserved.