Controlling microencapsulation and release of micronized proteins using poly(ethylene glycol) and electrospraying

The fabrication of tailored microparticles for delivery of therapeutics is a challenge relying upon a complex interplay between processing parameters and materials properties. The emerging use of electrospraying allows better tailoring of particle morphologies and sizes than current techniques, critical to reproducible release profiles. While dry encapsulation of proteins is essential for the release of active therapeutics from microparticles, it is currently uncharacterized in electrospraying. To this end, poly(ethylene glycol) (PEG) was assessed as a micronizing and solubilizing agent for dry protein encapsulation and release from electrosprayed particles made from polycaprolactone (PCL). The physical effect of PEG in protein-loaded poly(lactic-co-glycolic acid) (PLGA) particles was also studied, for comparison. The addition of 5–15 wt% PEG 6 kDa or 35 kDa resulted in reduced PCL particle sizes and broadened distributions, which could be improved by tailoring the electrospraying processing parameters, namely by reducing polymer concentration and increasing flow rate. Upon micronization, protein particle size was reduced to the micrometer domain, resulting in homogenous encapsulation in electrosprayed PCL microparticles. Microparticle size distributions were shown to be the most determinant factor for protein release by diffusion and allowed specific control of release patterns.

Slaving and release in co-infection control

Background Animal and human infection with multiple parasite species is the norm rather than the exception, and empirical studies and animal models have provided evidence for a diverse range of interactions among parasites. We demonstrate how an optimal control strategy should be tailored to the pathogen community and tempered by species-level knowledge of drug sensitivity with use of a simple epidemiological model of gastro-intestinal nematodes. Methods We construct a fully mechanistic model of macroparasite co-infection and use it to explore a range of control scenarios involving chemotherapy as well as improvements to sanitation. Results Scenarios are presented whereby control not only releases a more resistant parasite from antagonistic interactions, but risks increasing co-infection rates, exacerbating the burden of disease. In contrast, synergisms between species result in their becoming epidemiologically slaved within hosts, presenting a novel opportunity for controlling drug resistant parasites by targeting co-circulating species. Conclusions Understanding the effects on control of multi-parasite species interactions, and vice versa, is of increasing urgency in the advent of integrated mass intervention programmes.

Kissing fish: Rex Hunt, popular culture, sustainability and fishing practices

Natural resource managers and scientists focus on the behaviour of individual recreational fishers to understand environmental problems associated with this leisure activity. They do this in an effort to identify ways to change attitudes in order to facilitate environmentally friendly choices. This applied use of ABC psychology (attitude, behaviour, choice) has not delivered the expected results. This article offers a different approach by investigating an emergent practice in diverse fishing communities, rather than looking to the responsibility of the individual recreational fisher. Using practice theory, I trace the change from take-all to catch-and-release fishing in Australia by analysing the texts of celebrity fisher Rex Hunt, who is an advocate for releasing fish. I combine this with oral history testimony from a sample of recreational fishers from the broader Australian community to show how change happened. The practice of catch-and-release fishing emerged through the combination of sociotechnical and historically specific elements present in popular culture, including the media. Paying attention to the way different elements catalyse provides a rich account of the changing modes of sustainability in recreational fishing communities.

Analysing commercial catch and effort data from a penaeid trawl fishery: A comparison of linear models, mixed models, and generalised estimating equations approaches

Statistical methods are often used to analyse commercial catch and effort data to provide standardised fishing effort and/or a relative index of fish abundance for input into stock assessment models. Achieving reliable results has proved difficult in Australia's Northern Prawn Fishery (NPF), due to a combination of such factors as the biological characteristics of the animals, some aspects of the fleet dynamics, and the changes in fishing technology. For this set of data, we compared four modelling approaches (linear models, mixed models, generalised estimating equations, and generalised linear models) with respect to the outcomes of the standardised fishing effort or the relative index of abundance. We also varied the number and form of vessel covariates in the models. Within a subset of data from this fishery, modelling correlation structures did not alter the conclusions from simpler statistical models. The random-effects models also yielded similar results. This is because the estimators are all consistent even if the correlation structure is mis-specified, and the data set is very large. However, the standard errors from different models differed, suggesting that different methods have different statistical efficiency. We suggest that there is value in modelling the variance function and the correlation structure, to make valid and efficient statistical inferences and gain insight into the data. We found that fishing power was separable from the indices of prawn abundance only when we offset the impact of vessel characteristics at assumed values from external sources. This may be due to the large degree of confounding within the data, and the extreme temporal changes in certain aspects of individual vessels, the fleet and the fleet dynamics.

A maximum-likelihood method for estimating natural mortality and catchability coefficient from catch-and-effort data

A simple stochastic model of a fish population subject to natural and fishing mortalities is described. The fishing effort is assumed to vary over different periods but to be constant within each period. A maximum-likelihood approach is developed for estimating natural mortality (M) and the catchability coefficient (q) simultaneously from catch-and-effort data. If there is not enough contrast in the data to provide reliable estimates of both M and q, as is often the case in practice, the method can be used to obtain the best possible values of q for a range of possible values of M. These techniques are illustrated with tiger prawn (Penaeus semisulcatus) data from the Northern Prawn Fishery of Australia.

Facilities management action agenda : the Australian government and industry working together for improvement

This paper provides an overview of the Australian Government’s Facilities Management (FM) Action Agenda as announced in 2004 as a key policy plank designed to facilitate growth of the FM industry. The resulting consultation with industry leaders has seen the criterion and release in April 2005 of the FM Action Agenda’s strategic plan entitled ‘Managing the Built Environment’. This framework, representing a collaboration between the Australian Government, public and private sector stakeholders and Facility Management Association of Australia (FMA Australia) and other allied bodies, sets out to achieve the vision of a more “…productive and sustainable built environment…” through improved innovation, education and standards. The 36 month implementation phase is now underway and will take a multi-pronged approach to enhancing the recognition of the FM industry and removing impediments to its growth with a 20 point action plan across the following platforms: • Innovation – Improved appreciation of facility life cycles, and greater understanding of the key drivers of workplace productivity, and the improved application of information technology. • Education and Training – Improved access to dedicated FM education and training opportunities and creation clear career pathways into the profession. • Regulatory Reform – Explore opportunities to harmonise cross jurisdictional regulatory compliance requirements that have an efficiency impact on FM. • Sustainability – Improved utilization of existing knowledge and the development of tools and opportunities to improve the environmental performance of facilities. Additional information is available at www.fma.com.au

Legislative and security requirements of audit material for evidentiary purpose

This research used the Queensland Police Service, Australia, as a major case study. Information on principles, techniques and processes used, and the reason for the recording, storing and release of audit information for evidentiary purposes is reported. It is shown that Law Enforcement Agencies have a two-fold interest in, and legal obligation pertaining to, audit trails. The first interest relates to the situation where audit trails are actually used by criminals in the commission of crime and the second to where audit trails are generated by the information systems used by the police themselves in support of the recording and investigation of crime. Eleven court cases involving Queensland Police Service audit trails used in evidence in Queensland courts were selected for further analysis. It is shown that, of the cases studied, none of the evidence presented was rejected or seriously challenged from a technical perspective. These results were further analysed and related to normal requirements for trusted maintenance of audit trail information in sensitive environments with discussion on the ability and/or willingness of courts to fully challenge, assess or value audit evidence presented. Managerial and technical frameworks for firstly what is considered as an environment where a computer system may be considered to be operating “properly” and, secondly, what aspects of education, training, qualifications, expertise and the like may be considered as appropriate for persons responsible within that environment, are both proposed. Analysis was undertaken to determine if audit and control of information in a high security environment, such as law enforcement, could be judged as having improved, or not, in the transition from manual to electronic processes. Information collection, control of processing and audit in manual processes used by the Queensland Police Service, Australia, in the period 1940 to 1980 was assessed against current electronic systems essentially introduced to policing in the decades of the 1980s and 1990s. Results show that electronic systems do provide for faster communications with centrally controlled and updated information readily available for use by large numbers of users who are connected across significant geographical locations. However, it is clearly evident that the price paid for this is a lack of ability and/or reluctance to provide improved audit and control processes. To compare the information systems audit and control arrangements of the Queensland Police Service with other government departments or agencies, an Australia wide survey was conducted. Results of the survey were contrasted with the particular results of a survey, conducted by the Australian Commonwealth Privacy Commission four years previous, to this survey which showed that security in relation to the recording of activity against access to information held on Australian government computer systems has been poor and a cause for concern. However, within this four year period there is evidence to suggest that government organisations are increasingly more inclined to generate audit trails. An attack on the overall security of audit trails in computer operating systems was initiated to further investigate findings reported in relation to the government systems survey. The survey showed that information systems audit trails in Microsoft Corporation's “Windows” operating system environments are relied on quite heavily. An audit of the security for audit trails generated, stored and managed in the Microsoft “Windows 2000” operating system environment was undertaken and compared and contrasted with similar such audit trail schemes in the “UNIX” and “Linux” operating systems. Strength of passwords and exploitation of any security problems in access control were targeted using software tools that are freely available in the public domain. Results showed that such security for the “Windows 2000” system is seriously flawed and the integrity of audit trails stored within these environments cannot be relied upon. An attempt to produce a framework and set of guidelines for use by expert witnesses in the information technology (IT) profession is proposed. This is achieved by examining the current rules and guidelines related to the provision of expert evidence in a court environment, by analysing the rationale for the separation of distinct disciplines and corresponding bodies of knowledge used by the Medical Profession and Forensic Science and then by analysing the bodies of knowledge within the discipline of IT itself. It is demonstrated that the accepted processes and procedures relevant to expert witnessing in a court environment are transferable to the IT sector. However, unlike some discipline areas, this analysis has clearly identified two distinct aspects of the matter which appear particularly relevant to IT. These two areas are; expertise gained through the application of IT to information needs in a particular public or private enterprise; and expertise gained through accepted and verifiable education, training and experience in fundamental IT products and system.

Implications of patterns of carbon pools and fluxes across a semiarid environmental gradient

Landscape scale environmental gradients present variable spatial patterns and ecological processes caused by climate, topography and soil characteristics and, as such, offer candidate sites to study environmental change. Data are presented on the spatial pattern of dominant species, biomass, and carbon pools and the temporal pattern of fluxes across a transitional zone shifting from Great Basin Desert scrub, up through pinyon-juniper woodlands and into ponderosa pine forest and the ecotones between each vegetation type. The mean annual temperature (MAT) difference across the gradient is approximately 3 degrees C from bottom to top (MAT 8.5-5.5) and annual precipitation averages from 320 to 530 mm/yr, respectively. The stems of the dominant woody vegetation approach a random spatial pattern across the entire gradient, while the canopy cover shows a clustered pattern. The size of the clusters increases with elevation according to available soil moisture which in turn affects available nutrient resources. The total density of woody species declines with increasing soil moisture along the gl-adient, but total biomass increases. Belowground carbon and nutrient pools change from a heterogenous to a homogenous distribution on either side of the woodlands. Although temperature controls the: seasonal patterns of carbon efflux from the soils, soil moisture appears to be the primary driving variable, but response differs underneath the different dominant species, Similarly, decomposition of dominant litter occurs faster-at the cooler and more moist sites, but differs within sites due to litter quality of the different species. The spatial pattern of these communities provides information on the direction of future changes, The ecological processes that we documented are not statistically different in the ecotones as compared to the: adjoining communities, but are different at sites above the woodland than those below the woodland. We speculate that an increase in MAT will have a major impact on C pools and C sequestering and release processes in these semiarid landscapes. However, the impact will be primarily related to moisture availability rather than direct effects of an increase in temperature. (C) 1998 Elsevier Science B.V.

PLGA-based microparticles for the sustained release of BMP-2

The development of growth factor delivery strategies to circumvent the burst release phenomenon prevalent in most current systems has driven research towards encapsulating molecules in resorbable polymer matrices. For these polymer release techniques to be efficacious in a clinical setting, several key points need to be addressed. This present study has investigated the encapsulation of the growth factor, BMP-2 within PLGA/PLGA-PEG-PLGA microparticles. Morphology, size distribution, encapsulation efficiency and release kinetics were investigated and we have demonstrated a sustained release of bioactive BMP-2. Furthermore, biocompatibility of the PLGA microparticles was established and released BMP-2 was shown to promote the differentiation of MC3T3-E1 cells towards the osteogenic lineage to a greater extent than osteogenic supplements (as early as day 10 in culture), as determined using alkaline phosphatase and alizarin red assays. This study showcases a potential BMP-2 delivery system which may now be translated into more complex delivery systems, such as 3D, mechanically robust scaffolds for bone tissue regeneration applications.

The effects of bioactive akermanite on physiochemical, drug-delivery and biological properties of poly (lactide-co-glycolide) beads

Poly(lactide-co-glycolide) (PLGA) beads have been widely studied as a potential drug/protein carrier. The main shortcomings of PLGA beads are that they lack bioactivity and controllable drug-delivery ability, and their acidic degradation by-products can lead to pH decrease in the vicinity of the implants. Akermanite (AK) (Ca(2) MgSi(2) O(7) ) is a novel bioactive ceramic which has shown excellent bioactivity and degradation in vivo. This study aimed to incorporate AK to PLGA beads to improve the physiochemical, drug-delivery, and biological properties of PLGA beads. The microstructure of beads was characterized by SEM. The effect of AK incorporating into PLGA beads on the mechanical strength, apatite-formation ability, the loading and release of BSA, and the proliferation, and differentiation of bone marrow stromal cells (BMSCs) was investigated. The results showed that the incorporation of AK into PLGA beads altered the anisotropic microporous structure into homogenous one and improved their compressive strength and apatite-formation ability in simulated body fluids (SBF). AK neutralized the acidic products from PLGA beads, leading to stable pH value of 7.4 in biological environment. AK led to a sustainable and controllable release of bovine serum albumin (BSA) in PLGA beads. The incorporation of AK into PLGA beads enhanced the proliferation and alkaline phosphatase activity of BMSCs. This study implies that the incorporation of AK into PLGA beads is a promising method to enhance their physiochemical and biological property. AK/PLGA composite beads are a potential bioactive drug-delivery system for bone tissue repair.

Investigation of electrophoretic loading and enhanced mechanical properties of hydrogels for delivery of therapeutic proteins

Hydrogels, which are three-dimensional crosslinked hydrophilic polymers, have been used and studied widely as vehicles for drug delivery due to their good biocompatibility. Traditional methods to load therapeutic proteins into hydrogels have some disadvantages. Biological activity of drugs or proteins can be compromised during polymerization process or the process of loading protein can be really timeconsuming. Therefore, different loading methods have been investigated. Based on the theory of electrophoresis, an electrochemical gradient can be used to transport proteins into hydrogels. Therefore, an electrophoretic method was used to load protein in this study. Chemically and radiation crosslinked polyacrylamide was used to set up the model to load protein electrophoretically into hydrogels. Different methods to prepare the polymers have been studied and have shown the effect of the crosslinker (bisacrylamide) concentration on the protein loading and release behaviour. The mechanism of protein release from the hydrogels was anomalous diffusion (i.e. the process was non-Fickian). The UV-Vis spectra of proteins before and after reduction show that the bioactivities of proteins after release from hydrogel were maintained. Due to the concern of cytotoxicity of residual monomer in polyacrylamide, poly(2-hydroxyethyl- methacrylate) (pHEMA) was used as the second tested material. In order to control the pore size, a polyethylene glycol (PEG) porogen was introduced to the pHEMA. The hydrogel disintegrated after immersion in water indicating that the swelling forces exceeded the strength of the material. In order to understand the cause of the disintegration, several different conditions of crosslinker concentration and preparation method were studied. However, the disintegration of the hydrogel still occurred after immersion in water principally due to osmotic forces. A hydrogel suitable for drug delivery needs to be biocompatible and also robust. Therefore, an approach to improving the mechanical properties of the porogen-containing pHEMA hydrogel by introduction of an inter-penetrating network (IPN) into the hydrogel system has been researched. A double network was formed by the introduction of further HEMA solution into the system by both electrophoresis and slow diffusion. Raman spectroscopy was used to observe the diffusion of HEMA into the hydrogel prior to further crosslinking by ã-irradiation. The protein loading and release behaviour from the hydrogel showing enhanced mechanical property was also studied. Biocompatibility is a very important factor for the biomedical application of hydrogels. Different hydrogels have been studied on both a three-dimensional HSE model and a HSE wound model for their biocompatibilities. They did not show any detrimental effect to the keratinocyte cells. From the results reported above, these hydrogels show good biocompatibility in both models. Due to the advantage of the hydrogels such as the ability to absorb and deliver protein or drugs, they have potential to be used as topical materials for wound healing or other biomedical applications.

Optimum demand side response of smart grid with renewable energy source and electrical vehicles

The paper presents a demand side response scheme,which assists electricity consumers to proactively control own demands in such a way to deliberately avert congestion periods on the electrical network. The scheme allows shifting loads from peak to low demand periods in an attempt to flattening the national electricity requirement. The scheme can be concurrently used to accommodate the utilization of renewable energy sources,that might be available at user’s premises. In addition the scheme allows a full-capacity utilization of the available electrical infrastructure by organizing a wide-use of electric vehicles. The scheme is applicable in the Eastern and Southern States of Australia managed by the Australian Energy Market Operator. The results indicate the potential of the scheme to achieve energy savings and release capacity to accommodate renewable energy and electrical vehicle technologies.

The relationship between lower intelligence, crime and custodial outcomes : a brief literary review of a vulnerable group

The relationship between intellectual functioning and criminal offending has received considerable focus within the literature. While there remains debate regarding the existence (and strength) of this relationship, there is a wider consensus that individuals with below average functioning (in particular cognitive impairments) are disproportionately represented within the prison population. This paper focuses on research that has implications for the effective management of lower functioning individuals within correctional environments as well as the successful rehabilitation and release of such individuals back into the community. This includes a review of the literature regarding the link between lower intelligence and offending and the identification of possible factors that either facilitate (or confound) this relationship. The main themes to emerge from this review are that individuals with lower intellectual functioning continue to be disproportionately represented in custodial settings and that there is a need to increase the provision of specialised programs to cater for their needs. Further research is also needed into a range of areas including: (1) the reason for this over-representation in custodial settings, (2) the existence and effectiveness of rehabilitation and release programs that cater for lower IQ offenders, (3) the effectiveness of custodial alternatives for this group (e.g. intensive corrections orders) and (4) what post-custodial release services are needed to reduce the risk of recidivism.

Exercise-induced alterations in neutrophil degranulation and respiratory burst activity : possible mechanisms of action

Neutrophils constitute 50-60% of all circulating leukocytes; they present the first line of microbicidal defense and are involved in inflammatory responses. To examine immunocompetence in athletes, numerous studies have investigated the effects of exercise on the number of circulating neutrophils and their response to stimulation by chemotactic stimuli and activating factors. Exercise causes a biphasic increase in the number of neutrophils in the blood, arising from increases in catecholamine and cortisol concentrations. Moderate intensity exercise may enhance neutrophil respiratory burst activity, possibly through increases in the concentrations of growth hormone and the inflammatory cytokine IL-6. In contrast, intense or long duration exercise may suppress neutrophil degranulation and the production of reactive oxidants via elevated circulating concentrations of epinephrine (adrenaline) and cortisol. There is evidence of neutrophil degranulation and activation of the respiratory burst following exercise-induced muscle damage. In principle, improved responsiveness of neutrophils to stimulation following exercise of moderate intensity could mean that individuals participating in moderate exercise may have improved resistance to infection. Conversely, competitive athletes undertaking regular intense exercise may be at greater risk of contracting illness. However, there are limited data to support this concept. To elucidate the cellular mechanisms involved in the neutrophil responses to exercise, researchers have examined changes in the expression of cell membrane receptors, the production and release of reactive oxidants and more recently, calcium signaling. The investigation of possible modifications of other signal transduction events following exercise has not been possible because of current methodological limitations. At present, variation in exercise-induced alterations in neutrophil function appears to be due to differences in exercise protocols, training status, sampling points and laboratory assay techniques.

Delivery of dimethyloxallyl glycine in mesoporous bioactive glass scaffolds to improve angiogenesis and osteogenesis of human bone marrow stromal cells

Development of hypoxia-mimicking bone tissue engineering scaffolds is of great importance in stimulating angiogenesis for bone regeneration. Dimethyloxallyl glycine (DMOG) is a cell-permeable, competitive inhibitor of hypoxia-inducible factor prolyl hydroxylase (HIF-PH), which can stabilize hypoxia-inducible factor 1α (HIF-1α) expression. The aim of this study was to develop hypoxia-mimicking scaffolds by delivering DMOG in mesoporous bioactive glass (MBG) scaffolds and to investigate whether the delivery of DMOG could induce a hypoxic microenvironment for human bone marrow stromal cells (hBMSC). MBG scaffolds with varied mesoporous structures (e.g. surface area and mesopore volume) were prepared by controlling the contents of mesopore-template agent. The composition, large-pore microstructure and mesoporous properties of MBG scaffolds were characterized. The effect of mesoporous properties on the loading and release of DMOG in MBG scaffolds was investigated. The effects of DMOG delivery on the cell morphology, cell viability, HIF-1α stabilization, vascular endothelial growth factor (VEGF) secretion and bone-related gene expression (alkaline phosphatase, ALP; osteocalcin, OCN; and osteopontin, OPN) of hBMSC in MBG scaffolds were systematically investigated. The results showed that the loading and release of DMOG in MBG scaffolds can be efficiently controlled by regulating their mesoporous properties via the addition of different contents of mesopore-template agent. DMOG delivery in MBG scaffolds had no cytotoxic effect on the viability of hBMSC. DMOG delivery significantly induced HIF-1α stabilization, VEGF secretion and bone-related gene expression of hBMSC in MBG scaffolds in which DMOG counteracted the effect of HIF-PH and stabilized HIF-1α expression under normoxic condition. Furthermore, it was found that MBG scaffolds with slow DMOG release significantly enhanced the expression of bone-related genes more than those with instant DMOG release. The results suggest that the controllable delivery of DMOG in MBG scaffolds can mimic a hypoxic microenvironment, which not only improves the angiogenic capacity of hBMSC, but also enhances their osteogenic differentiation.