Development of a polymer theranostic for prostate cancer

Theranostics offers an improved treatment strategy for prostate cancer by facilitating simultaneous targeting of tumour cells with subsequent drug delivery and imaging. In this report we describe the synthesis of hyperbranched polymers that are biocompatible, can specifically target and be internalised by prostate cancer cells (through targeting of prostate-specific membrane antigen – PSMA) and ultimately facilitate controlled delivery of a model drug. The theranostic also incorporates a far-red fluorescent dye that allows tracking of the polymer via optical imaging. Controlled synthesis of the polymer is achieved via reversible addition fragmentation chain transfer polymerisation of polyethylene glycol monomethyl methacrylate, with ethylene glycol dimethacrylate as the branching agent. Incorporation of 20 mol% of an hydrazide-methacrylate monomer allows post-ligation of a model drug, fluorene-2-carboxaldehyde, through a hydrolytically-degradable hydrazone linkage. The rate of degradation of this particular linker was enhanced at endosomal pH (pH = 5.5) where [similar]95% of the model drug was released in 4 hours compared to less than 5% released over the same period at physiological pH. The theranostic showed high uptake into prostate cancer cells expressing prostate-specific membrane antigen, while minimal uptake was observed in PC3 cells negative for PSMA, highlighting the enhanced efficacy of the targeting ligand.

The ADAMTS1 protease gene is required for mammary tumor growth and metastasis

A disintegrin and metalloprotease with thrombospondin motifs protein 1 (ADAMTS1) is a protease commonly up-regulated in metastatic carcinoma. Its overexpression in cancer cells promotes experimental metastasis, but whether ADAMTS1 is essential for metastatic progression is unknown. To address this question, we investigated mammary cancer progression and spontaneous metastasis in the MMTV-PyMT mouse mammary tumor model in Adamts1 knockout mice. Adamts1−/−/PyMT mice displayed significantly reduced mammary tumor and lung metastatic tumor burden and increased survival, compared with their wild-type and heterozygous littermates. Histological examination revealed an increased proportion of tumors with ductal carcinoma in situ and a lower proportion of high-grade invasive tumors in Adamts1−/−/PyMT mice, compared with Adamts1+/+/PyMT mice. Increased apoptosis with unaltered proliferation and vascular density in the Adamts1−/−/PyMT tumors suggested that reduced cell survival accounts for the lower tumor burden in ADAMTS1-deficient mice. Furthermore, Adamts1−/− tumor stroma had significantly lesser amounts of proteolytically cleaved versican and increased numbers of CD45+ leukocytes. Characterization of immune cell gene expression indicated that cytotoxic cell activation was increased in Adamts1−/− tumors, compared with Adamts1+/+ tumors. This finding is supported by significantly elevated IL-12+ cell numbers in Adamts1−/− tumors. Thus, in vivo ADAMTS1 may promote mammary tumor growth and progression to metastasis in the PyMT model and is a potential therapeutic target to prevent metastatic breast cancer.

Leaders in Local : Exploring Consumers‘ Purchase Intentions of Locally Produced Foods

* Local foods are growing in importance in the mind set of the consumer – “the new organic” (McKenzie-Minifie, 2007) * Consumers are becoming more active in choosing alternative channels to purchase locally grown/produced foods Growth of farmer’s markets, roadside stalls, community gardens and *CSA programs * Supermarkets and grocers continue to tailor their assortments to include, ethnic, organic, natural and local foods to meet changing consumer needs * Australian research is limited, although one early study has found ‘buying locally produced foods’ was considered an important attribute (Lea & Worsley, 2007) * International research has tended to focus on COO effects, rather than region or local effects. (Insch & Florek, 2009) *Emerging research is beginning to explore consumer interest in ‘local’ over simply ‘domestic’ – although not specifically in food. (Hustvedt, Carroll & Bernard, 2013) * One study has examined differences in attitudes, subjective norms and intentions toward the purchase of locally produced foods. (Campbell, 2013)

A cost-effectiveness analysis of a telephone-linked care intervention for individuals with Type 2 diabetes

AIM: To assess the cost-effectiveness of an automated telephone-linked care intervention, Australian TLC Diabetes, delivered over 6 months to patients with established Type 2 diabetes mellitus and high glycated haemoglobin level, compared to usual care. METHODS: A Markov model was designed to synthesize data from a randomized controlled trial of TLC Diabetes (n=120) and other published evidence. The 5-year model consisted of three health states related to glycaemic control: 'sub-optimal' HbA1c ≥58mmol/mol (7.5%); 'average' ≥48-57mmol/mol (6.5-7.4%) and 'optimal' <48mmol/mol (6.5%) and a fourth state 'all-cause death'. Key outcomes of the model include discounted health system costs and quality-adjusted life years (QALYS) using SF-6D utility weights. Univariate and probabilistic sensitivity analyses were undertaken. RESULTS: Annual medication costs for the intervention group were lower than usual care [Intervention: £1076 (95%CI: £947, £1206) versus usual care £1271 (95%CI: £1115, £1428) p=0.052]. The estimated mean cost for intervention group participants over five years, including the intervention cost, was £17,152 versus £17,835 for the usual care group. The corresponding mean QALYs were 3.381 (SD 0.40) for the intervention group and 3.377 (SD 0.41) for the usual care group. Results were sensitive to the model duration, utility values and medication costs. CONCLUSION: The Australian TLC Diabetes intervention was a low-cost investment for individuals with established diabetes and may result in medication cost-savings to the health system. Although QALYs were similar between groups, other benefits arising from the intervention should also be considered when determining the overall value of this strategy.

PSMA-targeting iron oxide magnetic nanoparticles enhance MRI of preclinical prostate cancer

Aim Evaluate potential of newly-developed, biocompatible iron oxide magnetic nanoparticles (MNPs) conjugated with J591, an antibody to an extracellular epitope of prostate specific membrane antigen (PSMA), to enhance MRI of prostate cancer (PCa). Materials & Methods Specific binding to PSMA by J591-MNP was investigated in vitro. MRI studies were performed on orthotopic tumor-bearing NOD.SCID mice 2h and 24hr after intravenous injection of J591-MNPs, or non-targeting MNPs. Results and Conclusions In vitro, MNPs did not affect PCa cell viability, and conjugation to J591 did not compromise antibody specificity and enhanced cellular iron uptake. In vivo, PSMA-targeting MNPs increased MR contrast of tumors, but not by non-targeting MNPs. This provides proof-of-concept that PSMA-targeting MNPs have potential to enhance MR detection/localization of PCa.,

Enhancing MRI of prostate cancer using PSMA-targeting iron oxide magnetic nanoparticles

Introduction Novel imaging techniques for prostate cancer (PCa) are required to improve staging and real-time assessment of therapeutic response. We performed preclinical evaluation of newly-developed, biocompatible magnetic nanoparticles (MNPs) conjugated with J591, an antibody specific for prostate specific membrane antigen (PSMA), to enhance magnetic resonance imaging (MRI) of PCa. PSMA is expressed on ∼90% of PCa, including those that are castrate-resistant, rendering it as a rational target for PCa imaging. Materials and Methods The specificity of J591 for PSMA was confirmed by flow cytometric analysis of several PCa cell lines of known PSMA status. MNPs were prepared, engineered to the appropriate size, labeled with DiR fluorophore, and their toxicity to a panel of PC cells was assessed by in vitro Alamar Blue assay. Immunohistochemistry, fluorescence microscopy and Prussian Blue staining (iron uptake) were used to evaluate PSMA specificity of J591-MNP conjugates. In vivo MRI studies (16.4T MRI system) were performed using live immunodeficient mice bearing orthotopic LNCaP xenografts and injected intravenously with J591-MNPs or MNPs alone. Results MNPs were non-toxic to PCa cells. J591-MNP conjugates showed no compromise in specificity of binding to PSMA+ cells and showed enhanced iron uptake compared with MNPs alone. In vivo, tumour targeting (significant MR image contrast) was evident in mice injected with J591-MNPs, but not MNPs alone. Resected tumours from targeted mice had an accumulation of MNPs, not seen in normal control prostate. Conclusions Application of PSMA-targeting MNPs into conventional MRI has potential to enhance PCa detection and localization in real-time, improving patient management.

Recognising emotional expressions of complaining customers : A cross-cultural study

Purpose This study aims to test service providers’ ability to recognise non-verbal emotions in complaining customers of same and different cultures. Design/methodology/approach In a laboratory study, using a between-subjects experimental design (n = 153), we tested the accuracy of service providers’ perceptions of the emotional expressions of anger, fear, shame and happiness of customers from varying cultural backgrounds. After viewing video vignettes of customers complaining (with the audio removed), participants (in the role of service providers) assessed the emotional state of the customers portrayed in the video. Findings Service providers in culturally mismatched dyads were prone to misreading anger, happiness and shame expressed by dissatisfied customers. Happiness was misread in the displayed emotions of both dyads. Anger was recognisable in the Anglo customers but not Confucian Asian, while Anglo service providers misread both shame and happiness in Confucian Asian customers. Research limitations/implications The study was conducted in the laboratory and was based solely on participant’s perceptions of actors’ non-verbal facial expressions in a single encounter. Practical implications Given the level of ethnic differences in developed nations, a culturally sensitive workplace is needed to foster effective functioning of service employee teams. Ability to understand cultural display rules and to recognise and interpret emotions is an important skill for people working in direct contact with customers. Originality/value This research addresses the lack of empirical evidence for the recognition of customer emotions by service providers and the impact of cross-cultural differences.

The need for internal social marketing (ISM): extending the people focus to service employees

BreastScreen Queensland (BSQ) is a government-based health service that provides free breast cancer screening services to eligible women using digital mammography technology.' In 2007, BSQ launched its first social marketing campaign' aimed at achieving a 30 per cent increase in women's programme participation by addressing the barriers to regular screening and by dispelling myths about breast cancer (Tornabene 2010). 'The Facts' mass media social marketing campaign used a credible spokesperson, Australian journalist]ana Wendt, to deliver the call to action' Don't make excuses. Make an appointment'.

Can a text message a week improve breastfeeding?

Background Breastfeeding is recognised as the optimal method for feeding infants with health gains made by reducing infectious diseases in infancy; and chronic diseases, including obesity, in childhood, adolescence and adulthood. Despite this, exclusivity and duration in developed countries remains resistant to improvement. The objectives of this research were to test if an automated mobile phone text messaging intervention, delivering one text message a week, could increase “any” breastfeeding rates and improve breastfeeding self-efficacy and coping. Methods Women were eligible to participate if they were: over eighteen years; had an infant less than three months old; were currently breastfeeding; no diagnosed mental illness; and used a mobile phone . Women in the intervention group received MumBubConnect, a text messaging service with automated responses delivered once a week for 8 weeks. Women in the comparison group received their usual care and were sampled two years after the intervention group. Data collection included online surveys at two time points, week zero and week nine, to measure breastfeeding exclusivity and duration, coping, emotions, accountability and self-efficacy. A range of statistical analyses were used to test for differences between groups. Hierarchical regression was used to investigate change in breastfeeding outcome, between groups, adjusting for co-variates. Results The intervention group had 120 participants at commencement and 114 at completion, the comparison group had 114 participants at commencement and 86 at completion. MumBubConnect had a positive impact on the primary outcome of breastfeeding behaviors with women receiving the intervention more likely to continue exclusive breastfeeding; with a 6% decrease in exclusive breastfeeding in the intervention group, compared to a 14% decrease in the comparison group (p < 0.001). This remained significant after controlling for infant age, mother’s income, education and delivery type (p = 0.04). Women in the intervention group demonstrated active coping and were less likely to display emotions-focussed coping (p < .001). There was no discernible statistical effect on self-efficacy or accountability. Conclusions A fully automated text messaging services appears to improve exclusive breastfeeding duration. The service provides a well-accepted, personalised support service that empowers women to actively resolve breastfeeding issues. Trial registration Australian New Zealand Clinical Trials Registry: ACTRN12614001091695.

Metal Skin and the cinema of noise

In traditional communication and information theory, noise is the demon Other, an unwelcome disruption in the passage of information. Noise is "anything that is added to the signal between its transmission and reception that is not intended by the source...anything that makes the intended signal harder to decode accurately". It is in Michel Serres' formulation, the "third man" in dialogue who is always assumed, and whom interlocutors continually struggle to exclude. Noise is simultaneously a condition and a by-product of the act of communication, it represents the ever present possibility of disruption, interruption, misunderstanding. In sonic or musical terms noise is cacophony, dissonance. For economists, noise is an arbitrary element, both a barrier to the pursuit of wealth and a basis for speculation. For Mick (Jeremy Sims) and his mate Kev (Ben Mendelsohn) in David Caesar's Idiot Box (1996), as for Hando (Russell Crowe) and his gang of skinheads in Geoffrey Wright's Romper Stomper (1992), or Dazey (Ben Mendelsohn) and Joe (Aden Young) in Wright's Metal Skin (1994) and all those like them starved of (useful) information and excluded from the circuit - the information poor - their only option, their only point of intervention in the loop, is to make noise, to disrupt, to discomfort, to become Serres' "third man", "the prosopopoeia of noise" (5).

SHM through flexible vibration sensing technologies and robust safety evaluation paradigm

This research has successfully developed a novel synthetic structural health monitoring system model that is cost-effective and flexible in sensing and data acquisition; and robust in the structural safety evaluation aspect for the purpose of long-term and frequent monitoring of large-scale civil infrastructure during their service lives. Not only did it establish a real-world structural monitoring test-bed right at the heart of QUT Gardens Point Campus but it can also facilitate reliable and prompt protection for any built infrastructure system as well as the user community involved.

The psychological and economic factors that influence energy consumption habits of low-income earners

Social marketers and governments have often targeted hard to reach or vulnerable groups (Gordon et al., 2006) such as young adults and low income earners. Past research has shown that low-income earners are often at risk of poor health outcomes and diminished lifestyle (Hampson et al., 2009; Scott et al., 2012). Young adults (aged 18 to 35) are in a transition phase of their life where lifestyle preferences are still being formed and are thus a useful target for long-term sustainable change. An area of focus for all levels of government is the use of energy with an aim to reduce consumption. There is little research to date that combines both of these groups and in particular in the context of household energy usage. Research into financially disadvantaged consumers is challenging the notion that that low income consumer purchasing and usage of products and services is based upon economic status (Sharma et al., 2012). Prior research shows higher income earners view items such as televisions and computers as necessities rather than non-essential (Karlsson et al., 2004). Consistent with this is growing evidence that low income earners purchase non-essential, energy intensive electronic appliances such as multiple big screen TV sets and additional refrigerators. With this in mind, there is a need for knowledge about how psychological and economic factors influence the energy consumption habits (e.g. appliances on standby power, leaving appliances turned on, running multiple devices at one time) of low income earners. Thus, our study sought to address the research question of: What are the factors that influence young adult low-income earners energy habits?

The role of other people and emotion for blood donation : an altruistic social service

Blood donation is a critical part of health services with a viable blood supply underpinning an effective health program in any country. Typically blood is provided by voluntary donations from citizens and is therefore reliant on the goodwill and altruistic commitment of donors. In Australia, like many other developed nations, there are many challenges in maintaining a sufficient and sustainable blood supply. The Australian Red Cross Blood Service Donor and Community research group aim is to understand the barriers, motivations and perceptions of donors. Blood donation is a ‘people-processing’ service (Lovelock 1983, Russell-Bennett et al 2013) with the marketing exchange relating to bodily fluid rather than money and is an altruistic social service that has no direct benefit for the customer donor rather the benefit is for other people and society (Kotler and Zaltman 1971). Emotion has been shown to be a motivator and a barrier in a variety of Blood Service studies, this is a key insight that is further explored in the current study. Other key social factors that impact blood donor behavior are classified as social because they involve perceptions of other people’s beliefs and responses (such as moral or subjective norms), peer pressure, other people’s expectations and other people as a form of support. Given that emotions are social phenomena (Parkinson 1996), this study focuses on the role of other people in the blood donation process and how other people relates to the emotional experience of blood donors. We argue in this paper that overcoming emotional barriers to blood donation by leveraging the role of other people will influence low donation rates in Australia. To date, there has been little evidence in service research that identifies. In this paper we explore how other people influence the emotional experience of donors and how, donor emotions create the need for other people as a coping resource.

The effect of knee flexion contracture following total knee arthroplasty on the energy cost of walking.

This study evaluated the energy cost of walking (Cw) with knee flexion contractures (FC) simulated with a knee brace, in total knee arthroplasty (TKA) recipients (n=16) and normal controls (n=15), and compared it to baseline (no brace). There was no significant difference in Cw between the groups at baseline but TKA recipients walked slower (P=0.048) and with greater knee flexion in this condition (P=0.003). Simulated FC significantly increased Cw in both groups (TKA P=0.020, control P=0.002) and this occurred when FC exceeded 20° in the TKA group and 15° in the controls. Reported perceived exertion was only significantly increased by FC in the control group (control P<0.001, TKA P=0.058). Simulated knee FCs less than 20° do not increase Cw or perceived exertion in TKA recipients.

Commercial friendships between gay salesmen and straight female customers

Perhaps it is now sacrosanct in marketing to contemplate that many service encounters, especially those in retail settings, are social encounters in which bonds between and among customers and employees are critical drivers of consumption (Beatty et al., 1996; Rosenbaum, 2006). Indeed, within retail settings, it is often possible for salespeople and customers to form so-called “commercial friendships” (Price and Arnould, 1999). These friendships result in both salespeople and their customers having social interactions that are close to those experienced in personal friendships (Swan et al., 2001), and which are extremely satisfying for all parties. Outside of marketing, the social science literature (Grigoriou, 2004; Rumens, 2008; Russell, DelPriore, Butterfield, and Hill, 2013) and popular press (de la Cruz and Dolby, 2007; Hopcke and Rafaty, 1999; Tilmann-Healy, 2001, Whitney, 1990) is replete with knowledge regarding the “absolutely fabulous” friendships (Hopcke and Rafaty, 1999) that often form between gay men and straight women. In fact, Western culture regularly highlights the compatibility of gay men and straight women in film, television, and writing, to the extent that they have now influenced popular thinking on the topic, so that gay men and straight females are viewed as sharing common plights and interests (Rumens, 2008). Yet, thus far, marketing researchers have looked askance at the effect of friendships between gay male employees and heterosexual female customers in consumption settings, such as retail stores and boutiques. Indeed, with the exception of Peretz’s (1995) participant observation regarding how young and outwardly gay salesmen use their ambiguous gender to sell women’s clothing, in a Paris-based luxury boutique, any theoretical explorations regarding retail-based commercial friendships between gay salesmen and female customers are non-existent—until now. This research addresses this apparent chasm in the literature by putting forth an original framework that shows how the emotional closeness between gay salesmen and female customers, due to the absence of sexual interest and inter-female competition, results in an intense emotional closeness, that facilitates pleasurable retail transactions, customer satisfaction, loyalty, and positive word-of-mouth. In doing so, this work extends the commercial friendship paradigm by considering retail-based, commercial friendships between an under-researched marketplace dyad; gay men and straight females. It is worth noting here that some straight women may find the idea of commercial friendships with gay salesmen as undesirable, due to the very notion of having relationships with retail organizations or employees (Noble and Phillips, 2004), or a personal disdain for homosexuality.