Pharmaceutical review - Queensland Health’s experience

In 1990 Charles Hepler and Linda Strand published a sentinel paper and coined the term ‘Pharmaceutical Care’. This was defined as ‘that component of pharmacy practice which entails the direct interaction of the pharmacist with the patient for the purpose of caring for that patient’s drug-related needs’.1 In 1996 the Regional Pharmaceutical Officers’ Statement of Principles and Standards of Good Practice for Hospital Pharmacy in the UK stated that ‘All patients will receive the medicines to meet their agreed therapeutic objectives throughout the course of their treatment. This requires that the care plan for each patient identifies the correct choice of medication and is supported by systems for the provision of medicines…’

Projecting the new world city: The city as spectacle in an urban light festival

As a precursor to the 2014 G20 Leaders’ Summit held in Brisbane, Australia, the Queensland Government sponsored a program of G20 Cultural Celebrations, designed to showcase the Summit’s host city. The cultural program’s signature event was the Colour Me Brisbane festival, a two-week ‘citywide interactive light and projection installations’ festival that was originally slated to run from 24 October to 9 November, but which was extended due to popular demand to conclude with the G20 Summit itself on 16 November. The Colour Me Brisbane festival comprised a series projection displays that promoted visions of the city’s past, present, and future at landmark sites and iconic buildings throughout the city’s central business district and thus transformed key buildings into forms of media architecture. In some instances the media architecture installations were interactive, allowing the public to control aspects of the projections through a computer interface situated in front of the building; however, the majority of the installations were not interactive in this sense. The festival was supported by a website that included information regarding the different visual and interactive displays and links to social media to support public discussion regarding the festival (Queensland Government 2014). Festival-goers were also encouraged to follow a walking-tour map of the projection sites that would take them on a 2.5 kilometre walk from Brisbane’s cultural precinct, through the city centre, concluding at parliament house. In this paper, we investigate the Colour Me Brisbane festival and the broader G20 Cultural Celebrations as a form of strategic placemaking—designed, on the one hand, to promote Brisbane as a safe, open, and accessible city in line with the City Council’s plan to position Brisbane as a ‘New World City’ (Brisbane City Council 2014). On the other hand, it was deployed to counteract growing local concerns and tensions over the disruptive and politicised nature of the G20 Summit by engaging the public with the city prior to the heightened security and mobility restrictions of the Summit weekend. Harnessing perspectives from media architecture (Brynskov et al. 2013), urban imaginaries (Cinar & Bender 2007), and social media analysis, we take a critical approach to analysing the government-sponsored projections, which literally projected the city onto itself, and public responses to them via the official, and heavily promoted, social media hashtags (#colourmebrisbane and #g20cultural). Our critical framework extends the concepts of urban phantasmagoria and urban imaginaries into the emerging field of media architecture to scrutinise its potential for increased political and civic engagement. Walter Benjamin’s concept of phantasmagoria (Cohen 1989; Duarte, Firmino, & Crestani 2014) provides an understanding of urban space as spectacular projection, implicated in commodity and techno-culture. The concept of urban imaginaries (Cinar & Bender 2007; Kelley 2013)—that is, the ways in which citizens’ experiences of urban environments are transformed into symbolic representations through the use of imagination—similarly provides a useful framing device in thinking about the Colour Me Brisbane projections and their relation to the construction of place. Employing these critical frames enables us to examine the ways in which the installations open up the potential for multiple urban imaginaries—in the sense that they encourage civic engagement via a tangible and imaginative experience of urban space—while, at the same time, supporting a particular vision and way of experiencing the city, promoting a commodified, sanctioned form of urban imaginary. This paper aims to dissect the urban imaginaries intrinsic to the Colour Me Brisbane projections and to examine how those imaginaries were strategically deployed as place-making schemes that choreograph reflections about and engagement with the city.

Vascular endothelial growth factor is an autocrine growth factor, signaling through neuropilin-1 in non-small cell lung cancer

Background The VEGF pathway has become an important therapeutic target in lung cancer, where VEGF has long been established as a potent pro-angiogenic growth factor expressed by many types of tumors. While Bevacizumab (Avastin) has proven successful in increasing the objective tumor response rate and in prolonging progression and overall survival in patients with NSCLC, the survival benefit is however relatively short and the majority of patients eventually relapse. The current use of tyrosine kinase inhibitors alone and in combination with chemotherapy has been underwhelming, highlighting an urgent need for new targeted therapies. In this study, we examined the mechanisms of VEGF-mediated survival in NSCLC cells and the role of the Neuropilin receptors in this process. Methods NSCLC cells were screened for expression of VEGF and its receptors. The effects of recombinant VEGF and its blockade on lung tumor cell proliferation and cell cycle were examined. Phosphorylation of Akt and Erk1/2 proteins was examined by high content analysis and confocal microscopy. The effects of silencing VEGF on cell proliferation and survival signaling were also assessed. A Neuropilin-1 stable-transfected cell line was generated. Cell growth characteristics in addition to pAkt and pErk1/2 signaling were studied in response to VEGF and its blockade. Tumor growth studies were carried out in nude mice following subcutaneous injection of NP1 over-expressing cells. Results Inhibition of the VEGF pathway with anti-VEGF and anti-VEGFR-2 antibodies or siRNA to VEGF, NP1 and NP2 resulted in growth inhibition of NP1 positive tumor cell lines associated with down-regulation of PI3K and MAPK kinase signaling. Stable transfection of NP1 negative cells with NP1 induced proliferation in vitro, which was further enhanced by exogenous VEGF. In vivo, NP1 over-expressing cells significantly increased tumor growth in xenografts compared to controls. Conclusions Our data demonstrate that VEGF is an autocrine growth factor in NSCLC signaling, at least in part, through NP1. Targeting this VEGF receptor may offer potential as a novel therapeutic approach and also support the evaluation of the role of NP1 as a biomarker predicting sensitivity or resistance to VEGF and VEGFR-targeted therapies in the clinical arena.

Gamifying collective intelligence for the common good

The rise of the mobile internet enables the creation of applications that provide new and easier ways for people to organise themselves, raise issues, take action and interact with their city. At the same time, society faces new problems that can only be solved when citizens work together. Nevertheless, a lack of motivation or knowledge often prevents many citizens from regularly contributing to the common good. In this position paper, we present DoGood – a mobile app – as a socio-technological system that aims at supporting the collective intelligence of citizens in their pursuit of civic engagement and civic collaboratories. Our study asks to what extent gamification can motivate users to “do good” deeds. The DoGood app uses gamified elements to encourage citizens to submit and promote their civic activities as well as to join the activities of others. Gamification is sometimes criticised for simply adding a limited number of game elements, such as leaderboards, on top of an existing experience with the hope of increasing motivation. However, in the case of the DoGood app, the process of game design was an integral part of the development, and the gamified elements target the user’s intrinsic motivations instead of providing them with an external reward. In this paper, we present design elements of the app and discuss their potential to support collective intelligence for the common good.

Assessment of fundamental movement skills in childhood cancer patients

Background The improved treatment protocols and subsequent improved survival rates amongst childhood cancer patients has shifted the focus towards the long-term consequences arising from cancer treatment. Children who have completed cancer treatment are at a greater risk of delayed development, diminished functioning, disability, compromised fundamental movement skill (FMS) attainment and long term chronic health conditions. The aim of the study was to compare FMS of childhood cancer patients with an aged matched healthy reference group. Methods Pediatric cancer patients aged 5-8 years of age (n=26; median age 6.91 years), who completed cancer treatment (<5 years) at the Sydney Children’s Hospital were assessed performing 7 key FMS; sprint, side-gallop, vertical-jump, catch, over-arm throw, kick and leap. Results were compared to the reference group (n=430; 6.56 years). Results Childhood cancer patients scored significantly lower on 3 out of 7 FMS tests when compared to the reference group. These results equated to a significantly lower overall score for FMS. Conclusion This study highlighted the significant deficits in FMS within pediatric patients having completed cancer treatment. In order to reduce the occurrence of significant FMS deficits in this population, FMS interventions maybe warranted to assist in recovery from childhood cancer, prevent late effects and improve the quality of life in survivors of childhood cancer.

The High Court of Australia and the Marlboro Man: The Battle Over the Plain Packaging of Tobacco Products

In 2012, the High Court of Australia handed down a landmark decision on the plain packaging of tobacco products. This chapter considers the historic ruling in the case of JT International SA v Commonwealth; British American Tobacco Australasia Ltd v Commonwealth. This chapter explores several themes in the decision. First, it highlights the historical work by the High Court of Australia on the role of health regulation, the use of health warnings, and tobacco control. Second, the chapter considers the High Court of Australia's view that intellectual property law promotes the public interest.Third, it explores the High Court of Australia’s analysis of the constitutional law on acquisition of property on just terms. Finally, this chapter contends that the High Court of Australia's ruling on plain packaging of tobacco products will spark an 'Olive Revolution' — and will encourage superior courts and policy-makers to follow suit.

Combining meta- and mega-analytic approaches for multi-site diffusion imaging based genetic studies: From the enigma-DTI working group

Meta-analyses estimate a statistical effect size for a test or an analysis by combining results from multiple studies without necessarily having access to each individual study's raw data. Multi-site meta-analysis is crucial for imaging genetics, as single sites rarely have a sample size large enough to pick up effects of single genetic variants associated with brain measures. However, if raw data can be shared, combining data in a "mega-analysis" is thought to improve power and precision in estimating global effects. As part of an ENIGMA-DTI investigation, we use fractional anisotropy (FA) maps from 5 studies (total N=2, 203 subjects, aged 9-85) to estimate heritability. We combine the studies through meta-and mega-analyses as well as a mixture of the two - combining some cohorts with mega-analysis and meta-analyzing the results with those of the remaining sites. A combination of mega-and meta-approaches may boost power compared to meta-analysis alone.

Multi-site genetic analysis of diffusion images and voxelwise heritability analysis: A pilot project of the ENIGMA-DTI working group

The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium was set up to analyze brain measures and genotypes from multiple sites across the world to improve the power to detect genetic variants that influence the brain. Diffusion tensor imaging (DTI) yields quantitative measures sensitive to brain development and degeneration, and some common genetic variants may be associated with white matter integrity or connectivity. DTI measures, such as the fractional anisotropy (FA) of water diffusion, may be useful for identifying genetic variants that influence brain microstructure. However, genome-wide association studies (GWAS) require large populations to obtain sufficient power to detect and replicate significant effects, motivating a multi-site consortium effort. As part of an ENIGMA-DTI working group, we analyzed high-resolution FA images from multiple imaging sites across North America, Australia, and Europe, to address the challenge of harmonizing imaging data collected at multiple sites. Four hundred images of healthy adults aged 18-85 from four sites were used to create a template and corresponding skeletonized FA image as a common reference space. Using twin and pedigree samples of different ethnicities, we used our common template to evaluate the heritability of tract-derived FA measures. We show that our template is reliable for integrating multiple datasets by combining results through meta-analysis and unifying the data through exploratory mega-analyses. Our results may help prioritize regions of the FA map that are consistently influenced by additive genetic factors for future genetic discovery studies. Protocols and templates are publicly available at (http://enigma.loni.ucla.edu/ongoing/dti-working-group/).

Multi-site study of additive genetic effects on fractional anisotropy of cerebral white matter: Comparing meta and megaanalytical approaches for data pooling

Combining datasets across independent studies can boost statistical power by increasing the numbers of observations and can achieve more accurate estimates of effect sizes. This is especially important for genetic studies where a large number of observations are required to obtain sufficient power to detect and replicate genetic effects. There is a need to develop and evaluate methods for joint-analytical analyses of rich datasets collected in imaging genetics studies. The ENIGMA-DTI consortium is developing and evaluating approaches for obtaining pooled estimates of heritability through meta-and mega-genetic analytical approaches, to estimate the general additive genetic contributions to the intersubject variance in fractional anisotropy (FA) measured from diffusion tensor imaging (DTI). We used the ENIGMA-DTI data harmonization protocol for uniform processing of DTI data from multiple sites. We evaluated this protocol in five family-based cohorts providing data from a total of 2248 children and adults (ages: 9-85) collected with various imaging protocols. We used the imaging genetics analysis tool, SOLAR-Eclipse, to combine twin and family data from Dutch, Australian and Mexican-American cohorts into one large "mega-family". We showed that heritability estimates may vary from one cohort to another. We used two meta-analytical (the sample-size and standard-error weighted) approaches and a mega-genetic analysis to calculate heritability estimates across-population. We performed leave-one-out analysis of the joint estimates of heritability, removing a different cohort each time to understand the estimate variability. Overall, meta- and mega-genetic analyses of heritability produced robust estimates of heritability.

Grassland productivity limited by multiple nutrients

Terrestrial ecosystem productivity is widely accepted to be nutrient limited1. Although nitrogen (N) is deemed a key determinant of aboveground net primary production (ANPP)2,3, the prevalence of co-limitation by N and phosphorus (P) is increasingly recognized4,​5,​6,​7,​8. However, the extent to which terrestrial productivity is co-limited by nutrients other than N and P has remained unclear. Here, we report results from a standardized factorial nutrient addition experiment, in which we added N, P and potassium (K) combined with a selection of micronutrients (K+μ), alone or in concert, to 42 grassland sites spanning five continents, and monitored ANPP. Nutrient availability limited productivity at 31 of the 42 grassland sites. And pairwise combinations of N, P, and K+μ co-limited ANPP at 29 of the sites. Nitrogen limitation peaked in cool, high latitude sites. Our findings highlight the importance of less studied nutrients, such as K and micronutrients, for grassland productivity, and point to significant variations in the type and degree of nutrient limitation. We suggest that multiple-nutrient constraints must be considered when assessing the ecosystem-scale consequences of nutrient enrichment.

Plant species’ origin predicts dominance and response to nutrient enrichment and herbivores in global grasslands

Exotic species dominate many communities; however the functional significance of species’ biogeographic origin remains highly contentious. This debate is fuelled in part by the lack of globally replicated, systematic data assessing the relationship between species provenance, function and response to perturbations. We examined the abundance of native and exotic plant species at 64 grasslands in 13 countries, and at a subset of the sites we experimentally tested native and exotic species responses to two fundamental drivers of invasion, mineral nutrient supplies and vertebrate herbivory. Exotic species are six times more likely to dominate communities than native species. Furthermore, while experimental nutrient addition increases the cover and richness of exotic species, nutrients decrease native diversity and cover. Native and exotic species also differ in their response to vertebrate consumer exclusion. These results suggest that species origin has functional significance, and that eutrophication will lead to increased exotic dominance in grasslands.

Anatomical modelling of the pregnant radiotherapy patient

This study aimed to take existing anatomical models of pregnant women, currently used for radiation pro-tection and nuclear medicine dose calculations, and adapt them for use in the calculation of fetal dose from external beam radiotherapy (EBRT). The models investigated were ‘KATJA’, which was provided as an MCNPX geometry file, and ‘RPI-P6’, which was provided in a simple, voxelized bina-ry format. In-house code was developed, to convert both mod-els into an `egsphant’ format, suitable for use with DOSXYZnrc. The geometries and densities of the resulting phantoms were evaluated and found to accurately represent the source data. As an example of the use of the phantoms, the delivery of a cranial EBRT treatment was simulated using the BEAMnrc and DOSXYZnrc Monte Carlo codes and the likely out-of-field doses to the fetus in each model was calculated. The results of these calculations showed good agreement (with-in one standard deviation) between the doses calculated in KATJA and PRI-P6, despite substantial anatomical differ-ences between the two models. For a 36 Gy prescription dose to a 233.2 cm3 target in the right brain, the mean doses calcu-lated in a region of interest covering the entire uterus were 1.0 +/- 0.6 mSv for KATJA and 1.3 +/- 0.9 mSv for RPI-P6. This work is expected to lead to more comprehensive studies of EBRT treatment plan design and its effects on fetal dose in the future.

Interplay of MLC, gantry and respiratory motion during DCAT delivery

This study investigated the possible interplay effects arising from the treatment of moving targets using the dynamic conformal arc therapy (DCAT) technique. Dose from a modulated test beam was measured, with and without phantom motion and with and without a 30o arc rotation, using a diode array placed on a sinusoidally moving platform. Measurements were repeated at five different collimator angles (0, 22.5, 45, 67.5 and 90o), at two different dose rates (300 and 600 MU/min). Results showed that the effect of respiratory motion on the measured dose distribution increased slightly when the beams were delivered as arcs, rather than with a static gantry angle, and that this effect increased substantially as the collimator angle was increased from 0o (MLC motion perpendicular to respiratory motion) to 90o (MLC motion parallel to respiratory motion). The dose oscillations arising from interplay between phantom and MLC motion were found to increase in magnitude when the dose rate was increased. These results led to the development of simple recommendations for minimizing the negative effects of motion interplay on DCAT dose distributions

The presence of executive deficits in patients with Obstructive Sleep Apnoea

Obstructive sleep apnoea (OSA) is a chronic condition in which the upper airways collapse repeatedly during sleep, completely or partially obstructing breathing. This obstruction leads to chronic intermittent hypoxia and severe sleep fragmentation, disrupting the restorative functions of sleep. Beebe and Gozal (2002)a developed a theory which hypothesises that disruption of the restorative functions of sleep lead to a chronic low level brain damage most evident in executive functions (EF). Neuropsychological testing of EF, volumetric MRI, magnetic resonance spectroscopy, event related potentials and CSF biomarkers all provide support for this theory. Little research has been done to explore the nature of the subjective complaint and it’s impact on the activities of daily living.