Chitosan as a wall material for a microencapsulated delivery system for Macrobrachium rosenbergii(de Man) larvae

Chitosan has beenwidely accepted as awall material for preparing microcapsules of various purposes in human medicine. The possibility of using chitosan as a wall material for microencapsulating nutrients and drugs for aquaculture purposes, speci¢cally to Macrobrachium rosenbergii larvae was evaluated in this study. Two types of chitosan-coated microcapsules were prepared using either acetone (MEC-A) or NaOH (MEC-N) as the cross-linking agents. They were compared with a microbound diet relative to total leaching of nutrients and free amino acids (FAA). Among the microcapsules, MEC-N showed the lowest level of total leaching of nutrients (23.3%) during 5 h of immersion in seawater and released 65% FAA after 60min. During laboratory trials,75% larvae had accepted the MEC-N capsule. The results of the study suggest that chitosan can be used as a wall material for preparing microcapsules to deliver drugs and nutrients to M. rosenbergii larvae.

Logistics Network Design with Differentiated Delivery Lead-Time: Benefits and Insights

Most logistics network design models assume exogenous customer demand that is independent of the service time or level. This paper examines the benefits of segmenting demand according to lead-time sensitivity of customers. To capture lead-time sensitivity in the network design model, we use a facility grouping method to ensure that the different demand classes are satisfied on time. In addition, we perform a series of computational experiments to develop a set of managerial insights for the network design decision making process.

Apatite-Polymer Composites for the Controlled Dual Delivery of BMP-2 and BMP-6 for Bone Tissue Engineering

The release of growth factors from tissue engineering scaffolds provides signals that influence the migration, differentiation, and proliferation of cells. The incorporation of a drug delivery platform that is capable of tunable release will give tissue engineers greater versatility in the direction of tissue regeneration. We have prepared a novel composite of two biomaterials with proven track records - apatite and poly(lactic-co-glycolic acid) (PLGA) – as a drug delivery platform with promising controlled release properties. These composites have been tested in the delivery of a model protein, bovine serum albumin (BSA), as well as therapeutic proteins, recombinant human bone morphogenetic protein-2 (rhBMP-2) and rhBMP-6. The controlled release strategy is based on the use of a polymer with acidic degradation products to control the dissolution of the basic apatitic component, resulting in protein release. Therefore, any parameter that affects either polymer degradation or apatite dissolution can be used to control protein release. We have modified the protein release profile systematically by varying the polymer molecular weight, polymer hydrophobicity, apatite loading, apatite particle size, and other material and processing parameters. Biologically active rhBMP-2 was released from these composite microparticles over 100 days, in contrast to conventional collagen sponge carriers, which were depleted in approximately 2 weeks. The released rhBMP-2 was able to induce elevated alkaline phosphatase and osteocalcin expression in pluripotent murine embryonic fibroblasts. To augment tissue engineering scaffolds with tunable and sustained protein release capabilities, these composite microparticles can be dispersed in the scaffolds in different combinations to obtain a superposition of the release profiles. We have loaded rhBMP-2 into composite microparticles with a fast release profile, and rhBMP-6 into slow-releasing composite microparticles. An equi-mixture of these two sets of composite particles was then injected into a collagen sponge, allowing for dual release of the proteins from the collagenous scaffold. The ability of these BMP-loaded scaffolds to induce osteoblastic differentiation in vitro and ectopic bone formation in a rat model is being investigated. We anticipate that these apatite-polymer composite microparticles can be extended to the delivery of other signalling molecules, and can be incorporated into other types of tissue engineering scaffolds.

Apatite-Polymer Composite Particles for Controlled Delivery of BMP-2: In Vitro Release and Cellular Response

Bone morphogenetic protein-2 (BMP-2) has the ability to induce osteoblast differentiation of undifferentiated cells, resulting in the healing of skeletal defects when delivered with a suitable carrier. We have applied a versatile delivery platform comprising a novel composite of two biomaterials with proven track records – apatite and poly(lactic-co-glycolic acid) (PLGA) – to the delivery of BMP-2. Sustained release of this growth factor was tuned with variables that affect polymer degradation and/or apatite dissolution, such as polymer molecular weight, polymer composition, apatite loading, and apatite particle size. The effect of released BMP-2 on C3H10T1/2 murine pluripotent mesenchymal cells was assessed by tracking the expression of osteoblastic makers, alkaline phosphatase (ALP) and osteocalcin. Release media collected over 100 days induced elevated ALP activity in C3H10T1/2 cells. The expression of osteocalcin was also upregulated significantly. These results demonstrated the potential of apatite-PLGA composite particles for releasing protein in bioactive form over extended periods of time.

Targeted Stimuli-Responsive Dextran Conjugates for Doxorubicin Delivery to Hepatocytes

A targeted, stimuli-responsive, polymeric drug delivery vehicle is being developed in our lab to help alleviate severe side-effects caused by narrow therapeutic window drugs. Targeting specific cell types or organs via proteins, specifically, lectin-mediated targeting holds potential due to the high specificity and affinity of receptor-ligand interactions, rapid internalization, and relative ease of processing. Dextran, a commercially available, biodegradable polymer has been conjugated to doxorubicin and galactosamine to target hepatocytes in a three-step, one-pot synthesis. The loading of doxorubicin and galactose on the conjugates was determined by absorbance at 485 nm and elemental analysis, respectively. Conjugation efficiency based on the amount loaded of each reactant varies from 20% to 50% for doxorubicin and from 2% to 20% for galactosamine. Doxorubicin has also been attached to dextran through an acid-labile hydrazide bond. Doxorubicin acts by intercalating with DNA in the nuclei of cells. The fluorescence of doxorubicin is quenched when it binds to DNA. This allows a fluorescence-based cell-free assay to evaluate the efficacy of the polymer conjugates where we measure the fluorescence of doxorubicin and the conjugates in increasing concentrations of calf thymus DNA. Fluorescence quenching indicates that our conjugates can bind to DNA. The degree of binding increases with polymer molecular weight and substitution of doxorubicin. In cell culture experiments with hepatocytes, the relative uptake of polymer conjugates was evaluated using flow cytometry, and the killing efficiency was determined using the MTT cell proliferation assay. We have found that conjugate uptake is much lower than that of free doxorubicin. Lower uptake of conjugates may increase the maximum dose of drug tolerated by the body. Also, non-galactosylated conjugate uptake is lower than that of the galactosylated conjugate. Microscopy indicates that doxorubicin localizes almost exclusively at the nucleus, whereas the conjugates are present throughout the cell. Doxorubicin linked to dextran through a hydrazide bond was used to achieve improved killing efficiency. Following uptake, the doxorubicin dissociates from the polymer in an endosomal compartment and diffuses to the nucleus. The LC₅₀ of covalently linked doxorubicin is 7.4 μg/mL, whereas that of hydrazide linked doxorubicin is 4.4 μg/mL.

Caches and Content Delivery

Getting content from server to client can be more complicated than we have discussed so far. This lecture discusses how caching and content delivery networks help to make the Web work.

Small-area variation in health care affecting the choice of cesarean delivery: the case of a Colombian health insurer

In the midst of health care reform, Colombia has succeeded in increasing health insurance coverage and the quality of health care. In spite of this, efficiency continues to be a matter of concern, and small-area variations in health care are one of the plausible causes of such inefficiencies. In order to understand this issue, we use individual data of all births from a Contributory-Regimen insurer in Colombia. We perform two different specifications of a multilevel logistic regression model. Our results reveal that hospitals account for 20% of variation on the probability of performing cesarean sections. Geographic area only explains 1/3 of the variance attributable to the hospital. Furthermore, some variables from both demand and supply sides are found to be also relevant on the probability of undergoing cesarean sections. This paper contributes to previous research by using a hierarchical model and by defining hospitals as cluster. Moreover, we also include clinical and supply induced demand variables.

La orientación en la Universidad de Jaén. 'Guidance delivery at University of Jaén'.

Incluye un anexo con los cuestionarios usados en la investigación. Resumen basado en el de los autores. Resumen y título en castellano y en inglés

Testing Delivery Systems in Transnational virtual learning: the vocational management training for the european tourism industry (VocMat) case study

This article discusses the lessons learned from developing and delivering the Vocational Management Training for the European Tourism Industry (VocMat) online training programme, which was aimed at providing flexible, online distance learning for the European tourism industry. The programme was designed to address managers ‘need for flexible, senior management level training which they could access at a time and place which fitted in with their working and non-work commitments. The authors present two main approaches to using the Virtual Learning Environment, the feedback from the participants, and the implications of online Technology in extending tourism training opportunities

Literature review and analysis of itinerant teachers of the hearing impaired located in the midwest: Service delivery model in education

The role and responsibilities of an itinerant teacher of students who are deaf or hard of hearing were investigated to create a database of information about the effective traits of successful itinerant teachers.

The Court of Justice of the European Union as a fundamental rights tribunal: challenges for the effective delivery of fundamental rights in the area of freedom, security and justice. CEPS Paper in Liberty and Security in Europe No. 49, 29 August 2012

This paper reflects on the challenges facing the effective implementation of the new EU fundamental rights architecture that emerged from the Lisbon Treaty. Particular attention is paid to the role of the Court of Justice of the European Union (CJEU) and its ability to function as a ‘fundamental rights tribunal’. The paper first analyses the praxis of the European Court of Human Rights in Strasbourg and its long-standing experience in overseeing the practical implementation of the European Convention for the Protection of Human Rights and Fundamental Freedoms. Against this analysis, it then examines the readiness of the CJEU to live up to its consolidated and strengthened mandate on fundamental rights as one of the prime guarantors of the effective implementation of the EU Charter of Fundamental Rights. We specifically review the role of ‘third-party interventions’ by non-governmental organisations, international and regional human rights actors as well as ‘interim relief measures’ when ensuring effective judicial protection of vulnerable individuals in cases of alleged violations of fundamental human rights. To flesh out our arguments, we rely on examples within the scope of the relatively new and complex domain of EU legislation, the Area of Freedom, Security and Justice (AFSJ), and its immigration, external border and asylum policies. In view of the fundamental rights-sensitive nature of these domains, which often encounter shifts of accountability and responsibility in their practical application, and the Lisbon Treaty’s expansion of the jurisdiction of the CJEU to interpret and review EU AFSJ legislation, this area can be seen as an excellent test case for the analyses at hand. The final section puts forth a set of policy suggestions that can assist the CJEU in the process of adjusting itself to the new fundamental rights context in a post-Lisbon Treaty setting.

Fine sediment delivery and transfer in lowland catchments: modelling suspended sediment concentrations in response to hydrological forcing

Fine sediment delivery to and storage in stream channel reaches can disrupt aquatic habitats, impact river hydromorphology, and transfer adsorbed nutrients and pollutants from catchment slopes to the fluvial system. This paper presents a modelling toot for simulating the time-dependent response of the fine sediment system in catchments, using an integrated approach that incorporates both land phase and in-stream processes of sediment generation, storage and transfer. The performance of the model is demonstrated by applying it to simulate in-stream suspended sediment concentrations in two lowland catchments in southern England, the Enborne and the Lambourn, which exhibit contrasting hydrological and sediment responses due to differences in substrate permeability. The sediment model performs well in the Enborne catchment, where direct runoff events are frequent and peak suspended sediment concentrations can exceed 600 mg l(-1). The general trends in the in-stream concentrations in the Lambourn catchment are also reproduced by the model, although the observed concentrations are low (rarely exceeding 50 mg l(-1)) and the background variability in the concentrations is not fully characterized by the model. Direct runoff events are rare in this highly permeable catchment, resulting in a weak coupling between the sediment delivery system and the catchment hydrology. The generic performance of the model is also assessed using a generalized sensitivity analysis based on the parameter bounds identified in the catchment applications. Results indicate that the hydrological parameters contributing to the sediment response include those controlling (1) the partitioning of runoff between surface and soil zone flows and (2) the fractional loss of direct runoff volume prior to channel delivery. The principal sediment processes controlling model behaviour in the simulations are the transport capacity of direct runoff and the in-stream generation, storage and release of the fine sediment fraction. The in-stream processes appear to be important in maintaining the suspended sediment concentrations during low flows in the River Enborne and throughout much of the year in the River Lambourn. Copyright (c) 2007 John Wiley & Sons, Ltd.

Scope and Limitations of The Co-Drug Approach to Topical Drug Delivery

Many currently available drugs show unfavourable physicochemical properties for delivery into or across the skin and temporary chemical modulation of the penetrant is one option to achieve improved delivery properties. Pro-drugs are chemical derivatives of an active drug which is covalently bonded to an inactive pro-moiety in order to overcome pharmaceutical and pharmacokinetic barriers. A pro-drug relies upon conversion within the body to release the parent active drug (and pro-moiety) to elicit its pharmacological effect. The main drawback of this approach is that the pro-moiety is essentially an unwanted ballast which, when released, can lead to adverse effects. The term ‘co-drug’ refers to two or more therapeutic compounds active against the same disease bonded via a covalent chemical linkage and it is this approach which is reviewed for the first time in the current article. For topically applied co-drugs, each moiety is liberated in situ, either chemically or enzymatically, once the stratum corneum barrier has been overcome by the co-drug. Advantages include synergistic modulation of the disease process, enhancement of drug delivery and pharmacokinetic properties and the potential to enhance stability by masking of labile functional groups. The amount of published work on co-drugs is limited but the available data suggest the co-drug concept could provide a significant therapeutic improvement in dermatological diseases. However, the applicability of the co-drug approach is subject to strict limitations pertaining mainly to the availability of compatible moieties and physicochemical properties of the overall molecule.