The emerging role of extracellular vesicle-mediated drug resistance in cancers: Implications in advanced prostate cancer

Emerging evidence has shown that the extracellular vesicles (EVs) regulate various biological processes and can control cell proliferation and survival, as well as being involved in normal cell development and diseases such as cancers. In cancer treatment, development of acquired drug resistance phenotype is a serious issue. Recently it has been shown that the presence of multidrug resistance proteins such as Pgp-1 and enrichment of the lipid ceramide in EVs could have a role in mediating drug resistance. EVs could also mediate multidrug resistance through uptake of drugs in vesicles and thus limit the bioavailability of drugs to treat cancer cells. In this review, we discussed the emerging evidence of the role EVs play in mediating drug resistance in cancers and in particular the role of EVs mediating drug resistance in advanced prostate cancer. The role of EV-associated multidrug resistance proteins, miRNA, mRNA, and lipid as well as the potential interaction(s) among these factors was probed. Lastly, we provide an overview of the current available treatments for advanced prostate cancer, considering where EVs may mediate the development of resistance against these drugs.

Informed learning in the undergraduate classroom: The role of information experiences in shaping outcomes

This research aimed to inform the design of effective information literacy lessons in higher education. Phenomenography, a research approach designed to study human experience, was used to explore the experiences of a teacher and undergraduate students using information to learn about language and gender issues. The findings show that the way learners use information influences content-focused learning outcomes, and reveal an instructional pattern for enabling students to use information while becoming aware of the topic they are investigating. Based on the findings, a design model is offered in which learning outcomes are realized through targeted information literacy activities.

Role-based process view derivation and composition

The process view concept deploys a partial and temporal representation to adjust the visible view of a business process according to various perception constraints of users. Process view technology is of practical use for privacy protection and authorization control in process-oriented business management. Owing to complex organizational structure, it is challenging for large companies to accurately specify the diverse perception of different users over business processes. Aiming to tackle this issue, this article presents a role-based process view model to incorporate role dependencies into process view derivation. Compared to existing process view approaches, ours particularly supports runtime updates to the process view perceivable to a user with specific view merging operations, thereby enabling the dynamic tracing of process perception. A series of rules and theorems are established to guarantee the structural consistency and validity of process view transformation. A hypothetical case is conducted to illustrate the feasibility of our approach, and a prototype is developed for the proof-of-concept purpose.

The critical role of water in spider silk and its consequence for protein mechanics

Due to its remarkable mechanical and biological properties, there is considerable interest in understanding, and replicating, spider silk's stress-processing mechanisms and structure-function relationships. Here, we investigate the role of water in the nanoscale mechanics of the different regions in the spider silk fibre, and their relative contributions to stress processing. We propose that the inner core region, rich in spidroin II, retains water due to its inherent disorder, thereby providing a mechanism to dissipate energy as it breaks a sacrificial amide-water bond and gains order under strain, forming a stronger amide-amide bond. The spidroin I-rich outer core is more ordered under ambient conditions and is inherently stiffer and stronger, yet does not on its own provide high toughness. The markedly different interactions of the two proteins with water, and their distribution across the fibre, produce a stiffness differential and provide a balance between stiffness, strength and toughness under ambient conditions. Under wet conditions, this balance is destroyed as the stiff outer core material reverts to the behaviour of the inner core.

The Role of the Law in Communicating Patient Safety

This chapter considers the role of the law in communicating patient safety. Downie, Lahey, Ford, et al’s (2006) preventing, knowing and responding theoretical framework is adopted to classify the different elements of patient safety law. Rather than setting out all relevant patient safety laws in detail, this chapter highlights key legal strategies which are employed to: prevent the occurrence of patient safety incidents (preventing); support the discovery and open discussion of patient safety incidents when they do occur (knowing),; and guide responses after they occur (responding) (Downie, Lahey, Ford, et al 2006). The law is increasingly being invoked to facilitate open discussion of and communication surrounding patient safety. After highlighting some legal strategies used to communicate patient safety, two practice examples are presented. The practice examples highlight different aspects of patient safety law and are indicative of communication issues commonly faced in practice. The first practice example focuses on the role of the Ccoroner in communicating patient safety. This example highlights the investigative role of the law in relation to patient safety (knowing). It also showcases the preventing responding and preventing elements in respect of the significant number of communication errors that can occur in a multi-disciplinary, networked health system. The main focus of the second practice example is responding example illustrates how the law responds to health service providers’ and professionals’ miscommunication (and subsequent incidents) during treatment, however it also touches upon knowing and preventing.

Design-driven digital futures: The role of design-led innovation in the creation of online connected communities for new mobility solutions

Online communities have fundamentally changed how humans connected and are now so common they are fundamental to the human experience. As the Internet developed for Web 1.0 to Web 2.0, the functionality of these communities has far exceeded initial expectations. These communities have shifted from simply places to share information to ways to access products and services that bridge the online and offline worlds. This shift has led to the disruption of many industries with the transportation industry being one such sector. Both private transport providers and public transport systems face competition from online communities who are able to link services providers and customers more effectively and innovatively. These types of communities fall under what has been popularised as collaborative consumption or the sharing economy. The aim of this study is to explore the role of Design-led Innovation in the creation of digital futures, specifically online connected communities for successful new mobility solutions. To explore this proposition multiple data collection methods are proposed;Content Analysis, ii) A Comparative Qualitative Study consisting of Qualitative Interviews and Focus Groups / Design Workshops and iii) An Action Research Cycle of Embedded Practice. The multidisciplinary nature of this study grounds this research in a novel position contributing to new knowledge in both the field of design, and also a deeper understanding of the larger fast-growing online community phenomena.

Does calcium deposition play a role in the stability of atheroma? Location may be the key

Background: Rupture of vulnerable atheromatous plaque in the carotid and coronary arteries often leads to stroke and heart attack respectively. The role of calcium deposition and its contribution to plaque stability is controversial. This study uses both an idealized and a patient-specific model to evaluate the effect of a calcium deposit on the stress distribution within an atheromatous plaque. Methods: Using a finite-element method, structural analysis was performed on an idealized plaque model and the location of a calcium deposit within it was varied. In addition to the idealized model, in vivo high-resolution MR imaging was performed on 3 patients with carotid atheroma and stress distributions were generated. The individual plaques were chosen as they had calcium at varying locations with respect to the lumen and the fibrous cap. Results: The predicted maximum stress was increased by 47.5% when the calcium deposit was located in the thin fibrous cap in the model when compared with that in a model without a deposit. The result of adding a calcium deposit either to the lipid core or remote from the lumen resulted in almost no increase in maximal stress. Conclusion: Calcification at the thin fibrous cap may result in high stress concentrations, ultimately increasing the risk of plaque rupture. Assessing the location of calcification may, in the future, aid in the risk stratification of patients with carotid stenosis.

The role of H4 flagella in Escherichia coli ST131 virulence

Escherichia coli sequence type 131 (ST131) is a globally dominant multidrug resistant clone associated with urinary tract and bloodstream infections. Most ST131 strains exhibit resistance to multiple antibiotics and cause infections associated with limited treatment options. The largest sub-clonal ST131 lineage is resistant to fluoroquinolones, contains the type 1 fimbriae fimH30 allele and expresses an H4 flagella antigen. Flagella are motility organelles that contribute to UPEC colonisation of the upper urinary tract. In this study, we examined the specific role of H4 flagella in ST131 motility and interaction with host epithelial and immune cells. We show that the majority of H4-positive ST131 strains are motile and are enriched for flagella expression during static pellicle growth. We also tested the role of H4 flagella in ST131 through the construction of specific mutants, over-expression strains and isogenic mutants that expressed alternative H1 and H7 flagellar subtypes. Overall, our results revealed that H4, H1 and H7 flagella possess conserved phenotypes with regards to motility, epithelial cell adhesion, invasion and uptake by macrophages. In contrast, H4 flagella trigger enhanced induction of the anti-inflammatory cytokine IL-10 compared to H1 and H7 flagella, a property that may contribute to ST131 fitness in the urinary tract.

The role of engagement on stakeholder's satisfaction with the destination marketing organisation's performance

In the tourism literature there has been a lack of research related to stakeholders' satisfaction with destination marketing organisations (DMO). This study addresses this research gap, in the context of the national tourism office of Oman, by investigating the relationship between stakeholder's perceptions of DMO performance and their overall satisfaction with the DMO. Conceptually the study found DMO engagement with stakeholders to partially mediate satisfaction, a finding of relevance to destination marketers in other parts of the world. From a practical perspective the research was supported by the Oman national tourism office, which has only been in operation for 10 years.

Podiatry scope of practice: The role of gender in identification as a specialist

Background Ensuring efficient and effective delivery of health care to an aging population has been a major driver for a review of the health workforce in Australia. As part of this review a new National Registration and Accreditation Scheme (NRAS) has evolved with one goal being to improve workforce flexibility. With increased flexibility there have been discussions about the role specialist scopes of practice plays. This study explored the role of gender and other work related characteristics in relation to contemporary scope of podiatry practice and specialisation in Australia. Methods A cross sectional survey was administered through an on-line survey tool on behalf of the Australasian Podiatry Council. Descriptive data was collected over a three-week period. Queensland University of Technology Human Research Ethics approval was sought and confirmed exemption from review, exemption number 1400000791. Results Of the podiatrists participating in this survey (n=218), they were predominately female (66%), early career (34%, 0-9 years) and work in private practices (78%) in multi-podiatrists centres (41%). Relationship between clinical activities performed and “self-perception” of performing a “specialist role” was significant for practitioners who undertook treatment of specific patient groups. The largest area of interest was biomechanics (n=65), followed closely by diabetes (n=61), a third area identified was paediatrics (n=26). Self-perception of specialist status was compared with gender, years of experience, location, primary work environment and clinical practice. When practitioners are asked to categorise themselves to be either “generalist” or “specialist/ generalist with a special interest” podiatrist, male gender was identified as being the only factor which would predict perception of status; 64% males identified as specialist, as opposed to 49% of female survey respondents (Chi square, df = 1, P = 0.044). Self-perception of specialist status was not explained by years of experience, location, working in rural versus urban environment, state worked in, or part-time/full-time work status. Conclusions In conclusion; gender, work environment plus area of interest form a complex relationship, which appear to influence both perception and reality of service provision. Incorporation of specialisation activity (surgical podiatry along with endorsement for use of scheduled medicines) will have lasting impact on the scope of the podiatry profession in Australia. To meet community expectation and maintain high standards, the addition of new subspecialties may be indicated.

Sustainable me - a pharmacist’s role in reducing the carbon footprint of healthcare delivery

Introduction Climate change has been described as the most significant global health threat of the 21st century. Already, negative impacts on human health and wellbeing are being observed. These impacts present enormous challenges for the healthcare sector and the time has come for healthcare professionals to demonstrate leadership in addressing these challenges. Since any unsustainable organizational practices of healthcare organisations may ultimately have a negative impact on human health, there is an implicit moral obligation for these organisations and the people who work in them, to deliver healthcare more sustainably. If one considers that in 2010 pharmaceuticals comprised 22% of the carbon footprint of the NHS England (equating to 4.4 million tonnes of CO2 emissions) and 3% of England’s total carbon footprint (NHS Sustainable Development Unit, 2012), by reducing the carbon footprint of pharmaceuticals used in their healthcare organisations, pharmacists can have a significant impact on reducing the organisation’s total carbon footprint and ultimately on the public’s health. Aims The engagement of pharmacists with sustainability initiatives in the workplace has been largely unreported in international and national pharmacy journals. This paper aims to highlight the important role that pharmacists can play in helping to reduce the carbon footprint of healthcare delivery. Methods Literature was reviewed to identify areas where pharmacists could influence the more sustainable use of pharmaceuticals in their organisations. Discussion Much of the carbon footprint of pharmaceuticals is embedded carbon from their manufacture and delivery. Through efficient inventory management practices, pharmacists can reduce the number of orders and potentially reduce the number of deliveries required. Pharmacists can also help to reduce the amount of pharmaceutical waste generated. Of the waste that is generated, they can help improve the segregation of waste streams to increase the amount of non-contaminated packaging waste that is recycled and reduce the amount of pharmaceutical waste being incinerated or ending up in landfill. Reference NHS Sustainable Development Unit. (2012). Sustainability in the NHS Health Check 2012. NHS Sustainable Development Unit. Cambridge, UK: NHS Sustainable Devlopment Unit.

Neighborhood diversity, economic health and the role of the arts

Policymakers pursue a range of strategies aimed at diversifying neighborhoods despite research indicating the complicated and potentially damaging results of these efforts. One increasingly common approach is to incorporate the arts into planning efforts in the hope of enhancing diversity and catalyzing positive neighborhood change. Using data from the Cultural Data Project, we determine where newly established New York City art organizations locate in terms of neighborhood racial, income and industry diversity. We then analyze how diverse contexts interact with an arts presence to impact neighborhood economic health over time. We find that neighborhoods with high levels of racial diversity and low levels of income and industry diversity benefit most from an arts presence. However, the arts are attracted predominately to neighborhoods with moderate levels of racial diversity and high levels of income and industry diversity. This complicates the use of the arts as a tool in urban revitalization policy.

Is there a role for pharmacists in multidisciplinary health-care teams at community outreach events for the homeless?

Homelessness is a significant public health problem. It is well-documented that people experiencing homelessness exhibit more serious illnesses and have poorer health than the general population. The provision of services and interventions by health-care professionals, including pharmacists, may make a simple yet important contribution to improved health outcomes in those experiencing homelessness, but evidence of roles and interventions is limited and variable. In Australia, the Queensland University of Technology Health Clinic connects with the homeless community by taking part in community outreach events. This paper provides details of one such event, as well as the roles, interventions and experiences of pharmacists. Participation and inclusion of pharmacists in a multidisciplinary health-care team approach at homeless outreach events should be supported and encouraged.

The role of comfort in child restraint use practices

Suboptimal restraint use, particularly the incorrect use of restraints, is a significant and widespread problem among child vehicle occupants, and increases the risk of injury. Previous research has identified comfort as a potential factor influencing suboptimal restraint use. Both the real comfort experienced by the child and the parent’s perception of the child’s comfort are reported to influence the optimal use of restraints. Problems with real comfort may lead the child to misuse the restraint in their attempt to achieve better comfort whilst parent-perceived discomfort has been reported as a driver for premature graduation and inappropriate restraint choice. However, this work has largely been qualitative. There has been no research that objectively studies either the association between real and parent-perceived comfort, or any association between comfort and suboptimal restraint use. One barrier to such studies is the absence of validated tools for quantifying real comfort in children. We aimed to develop methods to examine both real and parent-perceived comfort and examine their effects on suboptimal restraint use. We conducted online parent surveys (n=470) to explore what drives parental perceptions of their child’s comfort in restraint systems (study 1) and used data from field observation studies (n=497) to examine parent-perceived comfort and its relationship with observed restraint use (study 2). We developed methods to measure comfort in children in a laboratory setting (n=14) using video analysis to estimate a Discomfort Avoidance Behaviour (DAB) score, pressure mapping and adapted survey tools to differentiate between comfortable and induced discomfort conditions (study 3). The DAB rate was then used to compare an integrated booster with an add-on booster (study 4) Preliminary analysis of our recent online survey of Australian parents (study 1) indicates that 23% of parents report comfort as a consideration when making a decision to change restraints. Logistic regression modelling of data collected during the field observation study (study 2) revealed that parent-perceived discomfort was not significantly associated with premature graduation. Contrary to expectation, children of parents who reported that their child was comfortable were almost twice as likely to have been incorrectly restrained (p<0.01, 95% CI 1.24 - 2.77).In the laboratory study (study 3) we found our adapted survey tools did not provide a reliable measurement of real comfort among children. However our DAB score was able to differentiate between comfortable and induced discomfort conditions and correlated well with pressure mapping. Preliminary results from the laboratory comparison study (study 4) indicate a positive correlation between DAB rate and use errors. In experiments conducted to date, we have seen a significantly higher DAB rate in the integrated booster compared to the add-on booster (p < 0.01). However, this needs to be confirmed in a naturalistic setting and in further experiments that take length of time under observation into account. Our results suggest that while some parents report concern about their child’s comfort, parent-reported comfort levels were not associated with restraint choice. If comfort is important for optimal restraint use, it is likely to be the real comfort of the child rather than that reported by the parent. The method we have developed for studying real comfort can be used in naturalistic studies involving child occupants to further understand this relationship. This work will be of interest to vehicle and child restraint manufacturers interested in improving restraint design for young occupants as well as researchers and other stakeholders interested in reducing the incidence of restraint misuse among children.

Rail fatigue and the role of impact forces

Fatigue of the steel in rails continues to be of major concern to heavy haul track owners despite careful selection and maintenance of rails. The persistence of fatigue is due in part to the erroneous assumption that the maximum loads on, and stresses in, the rails are predictable. Recent analysis of extensive wheel impact detector data from a number of heavy haul tracks has shown that the most damaging forces are in fact randomly distributed with time and location and can be much greater than generally expected. Large- scale Monte-Carlo simulations have been used to identify rail stresses caused by actual, measured distributions of wheel-rail forces on heavy haul tracks. The simulations show that fatigue failure of the rail foot can occur in situations which would be overlooked by traditional analyses. The most serious of these situations are those where track is accessed by multiple operators and in situations where there is a mix of heavy haul, general freight and/or passenger traffic. The least serious are those where the track is carrying single-operator-owned heavy haul unit trains. The paper shows how using the nominal maximum axle load of passing traffic, which is the key issue in traditional analyses, is insufficient and must be augmented with consideration of important operational factors. Ignoring such factors can be costly.