Electrospraying of polymers with therapeutic molecules : state of the art

The encapsulation and release of bioactive molecules from polymeric vehicles represents the holy grail of drug and growth factor delivery therapies, whereby sustained and controlled release is crucial in eliciting a positive therapeutic effect. To this end, electrospraying is rapidly emerging as a popular technology for the production of polymeric particles containing bioactive molecules. Compared with traditional emulsion fabrication techniques, electrospraying has the potential to reduce denaturation of protein drugs and affords tighter regulation over particle size distribution and morphology. In this article, we review the importance of the electrospraying parameters that enable reproducible tailoring of the particles' physical and in vitro drug release characteristics, along with discussion of existing in vivo data. Controlled morphology and monodispersity of particles can be achieved with electrospraying, with high encapsulation efficiencies and without unfavorable denaturation of bioactive molecules throughout the process. Finally, the combination of electrospraying with electrospun scaffolds, with an emphasis on tissue regeneration is reviewed, depicting a technique in its relative infancy but holding great promise for the future of regenerative medicine.

Women IN Sport or Women OR Sport - The search for work/sport/life balance.

The current ‘holy grail’ for our health and well-being centres around the search for, and establishment of, a work/life balance. For many individuals, this appears to be an ever-elusive goal – forever slipping from our grasp as we juggle the day-to-day battle for our attention and time from an array of sources. When we add the word ‘Women’ to this mix, often the number of sources related to these demands multiplies in alignment with the number of roles we fill. To take this to even another level, consider the addition of the words ‘Sport’ or ‘Elite Athlete’ to ‘Women’ and ‘Work/Life Balance’, and the search for the ‘holy grail’ becomes more literal! Many sportswomen at the elite level face significant challenges in balancing working to support themselves and/or their families, studying to lay the foundations of a post-sport career, (often) spending the equivalent of full-time hours training towards their sporting goals, and additionally investing in the things that are important for them outside of these two areas – the ‘Life’ component. Getting the work/life balance ‘balanced’ has been suggested to be a key component of investing in our health and well-being. The same is applicable to sportswomen, with the added suggestion that if the balance between work/sport/life is achieved, this can positively impact upon sporting performance itself. These ideas and observations will be explored via experience within the Australian elite sporting environment from a psychologist’s perspective, with questions and invitations for further discussion.

Achieving enterprise integration through software customization : part I-evidence from the field

Achieving business and IT integration is strategic goal for many organisations – it has almost become the ‘Holy Grail’ of organisational success. In this environment Enterprise Resource Planning (ERP) packages have become the defacto option for addressing this issue. Integration has come to mean adopting ERP, through configuration and without customization, but this all or nothing approach has proved difficult for many organisations. In part 1 of a 2 part update we provide evidence from the field that suggests that whilst costly, if managed appropriately, customization can have value in aiding organisational integration efforts. In part 2, we discuss in more detail the benefits and pitfalls involved in enacting a non-standard based integration strategy.

Once more into the mire, dear friends : determining the existence of a duty of care in negligence

There were signs in the 1997 High Court decision in Hill v Van Erp that the different members of the bench were beginning to move in the same direction when it came to the tort equivalent of the search for the Holy Grail, a common approach to the determination of the existence of a duty of care in negligence. However, the court's subsequent decision in Perre v Apand signaled a slide back to uncertainty with the seven judges favouring five different approaches. This Note examines those five approaches in the search for guidance for those at the "coalface" - litigants, their legal advisers and trial judges.

The sequence: Inside the race for the human genome

The human genome project was a grand scientific enterprise which attracted both hyperbole and ridicule alike. The project was lauded as “the moon shot of the life sciences”, the “holy grail of man”, “the code of codes”, and “the book of life”. Such rhetoric has also received scorn. President George Bush senior managed to deflate the pretensions of the project with the accidental slip that it was the “human gnome initiative”. In The Sequence, Kevin Davies seeks to go beyond such metaphors, and provide a candid and honest account of the race of the human genome project. The author is indebted to the authoritative book The Gene Wars, which considered the early struggles over the human genome project. Robert Cook-Deegan observes that there was initially much debate over whether there should be a Human Genome Project at all: The debate became one of “big” science versus “small” science. The reliance on systematic technology development and goal-directed gene-mapping efforts presaged a new style for biology, one that elicited excitement from those attracted to whiz-bang technologies but drew gasps of revulsion from those who aspired to cultivate biology on a more modest scale and with decentralized organisation. The battle was, among other things, over whose vision would control the budget and which scientific aesthetic would prevail.

Global trends in prescribing contact lenses for extended wear

Extended wear has long been the ‘holy grail’ of contact lenses by virtue of the increased convenience and freedom of lifestyle which they accord; however, this modality enjoyed only limited market success during the last quarter of the 20th century. The introduction of silicone hydrogel materials into the market at the beginning of this century heralded the promise of successful extended wear due to the superior oxygen performance of this lens type. To assess patterns of contact lens fitting, including extended wear, over the past decade, up to 1000 survey forms were sent to contact lens fitters in Australia, Canada, Japan, the Netherlands, Norway, the UK and the USA each year between 2000 and 2009. Practitioners were asked to record data relating to the first 10 contact lens fits or refits performed after receiving the survey form. Analysis of returned forms revealed that, averaged over this period, 9% of all soft lenses prescribed were for extended wear, with national figures ranging from 2% in Japan to 17% in Norway. The trend over the past decade has been for an increase from about 5% of all soft lens fits in 2000 to a peak of between 9 and 12% between 2002 and 2007, followed by a decline to around 7% in 2009. A person receiving extended wear lenses is likely to be an older female who is being refitted with silicone hydrogel lenses for full-time wear. Although extended wear has yet again failed to fulfil the promise of being the dominant contact lens wearing modality, it is still a viable option for many people.

Oxygen; my view

Oxygen has been the “holy grail” of contact lens wear for over 100 years, but it is just one piece of a complex jigsaw puzzle. Clearly, high oxygen transmissibility (Dk/t) silicone hydrogel lenses meet the oxygen needs of the cornea. The Dk/t of these lenses is over 75 Dk units, which is far above that of the “best” hydrogel lenses (30 Dk units). Clinical trials have failed to reveal any hypoxic problemswith silicone hydrogel lenses. Thus, conditions such as epithelial microcysts, limbal redness, hypoxic staining, stromal neovascularisation, oedema and endothelial polymegethism do not occur with these lenses. My view is that – looking at the “big picture” – we are far better off now that we have silicone hydrogel lenses.

Genome-wide association studies and musculoskeletal diseases

Bone and joint diseases are major causes of morbidity and mortality worldwide, and their prevalence is increasing as the average population age increases. Most common musculoskeletal diseases show significant heritability, and few have treatments that prevent disease or can induce true treatment-free, disease-free remission. Furthermore, despite valiant efforts of hypothesis-driven research, our understanding of the etiopathogenesis of these conditions is, with few exceptions, at best moderate. Therefore, there has been a long-standing interest in genetics research in musculoskeletal disease as a hypothesis-free method for investigating disease etiopathogenesis. Important contributions have been made through the identification of monogenic causes of disease, but the holy grail of human genetics research has been the identification of the genes responsible for common diseases. The development of genome-wide association (GWA) studies has revolutionized this field, and led to an explosion in the number of genes identified that are definitely involved in musculoskeletal disease pathogenesis. However, this approach will not identify all common disease genes, and although the current progress is exciting and proves the potential of this research discipline, other approaches will be required to identify many of the types of genetic variation likely to be involved.

The development of Monte Carlo techniques for the verification of radiotherapy treatments

Introduction: Recent advances in the planning and delivery of radiotherapy treatments have resulted in improvements in the accuracy and precision with which therapeutic radiation can be administered. As the complexity of the treatments increases it becomes more difficult to predict the dose distribution in the patient accurately. Monte Carlo (MC) methods have the potential to improve the accuracy of the dose calculations and are increasingly being recognised as the ‘gold standard’ for predicting dose deposition in the patient [1]. This project has three main aims: 1. To develop tools that enable the transfer of treatment plan information from the treatment planning system (TPS) to a MC dose calculation engine. 2. To develop tools for comparing the 3D dose distributions calculated by the TPS and the MC dose engine. 3. To investigate the radiobiological significance of any errors between the TPS patient dose distribution and the MC dose distribution in terms of Tumour Control Probability (TCP) and Normal Tissue Complication Probabilities (NTCP). The work presented here addresses the first two aims. Methods: (1a) Plan Importing: A database of commissioned accelerator models (Elekta Precise and Varian 2100CD) has been developed for treatment simulations in the MC system (EGSnrc/BEAMnrc). Beam descriptions can be exported from the TPS using the widespread DICOM framework, and the resultant files are parsed with the assistance of a software library (PixelMed Java DICOM Toolkit). The information in these files (such as the monitor units, the jaw positions and gantry orientation) is used to construct a plan-specific accelerator model which allows an accurate simulation of the patient treatment field. (1b) Dose Simulation: The calculation of a dose distribution requires patient CT images which are prepared for the MC simulation using a tool (CTCREATE) packaged with the system. Beam simulation results are converted to absolute dose per- MU using calibration factors recorded during the commissioning process and treatment simulation. These distributions are combined according to the MU meter settings stored in the exported plan to produce an accurate description of the prescribed dose to the patient. (2) Dose Comparison: TPS dose calculations can be obtained using either a DICOM export or by direct retrieval of binary dose files from the file system. Dose difference, gamma evaluation and normalised dose difference algorithms [2] were employed for the comparison of the TPS dose distribution and the MC dose distribution. These implementations are spatial resolution independent and able to interpolate for comparisons. Results and Discussion: The tools successfully produced Monte Carlo input files for a variety of plans exported from the Eclipse (Varian Medical Systems) and Pinnacle (Philips Medical Systems) planning systems: ranging in complexity from a single uniform square field to a five-field step and shoot IMRT treatment. The simulation of collimated beams has been verified geometrically, and validation of dose distributions in a simple body phantom (QUASAR) will follow. The developed dose comparison algorithms have also been tested with controlled dose distribution changes. Conclusion: The capability of the developed code to independently process treatment plans has been demonstrated. A number of limitations exist: only static fields are currently supported (dynamic wedges and dynamic IMRT will require further development), and the process has not been tested for planning systems other than Eclipse and Pinnacle. The tools will be used to independently assess the accuracy of the current treatment planning system dose calculation algorithms for complex treatment deliveries such as IMRT in treatment sites where patient inhomogeneities are expected to be significant. Acknowledgements: Computational resources and services used in this work were provided by the HPC and Research Support Group, Queensland University of Technology, Brisbane, Australia. Pinnacle dose parsing made possible with the help of Paul Reich, North Coast Cancer Institute, North Coast, New South Wales.

Effects of inhibitors of plasminogen activator, serine proteinases, and collagenase IV on the invasion of basement membranes by metastatic cells

Using both human and murine cell lines, we show that malignant cells are able to invade through basement membrane and also secrete elevated amounts of collagenase IV, an enzyme implicated in the degradation of basement membranes. Using serine proteinase inhibitors and antibodies to plasminogen activators as well as a newly described collagenase inhibitor we demonstrate that a protease cascade leads to the activation of an enzyme(s) that cleaves collagen IV. Inhibition at each step reduces the invasion of the tumor cells through reconstituted basement membrane in vitro. Treatment with a collagenase inhibitor reduced the incidence of lung lesions in mice given i.v. injections of malignant melanoma cells.