Development of reverse phase protein microarrays for clinical applications and patient-tailored therapy

While genomics provide important information about the somatic genetic changes, and RNA transcript profiling can reveal important expression changes that correlate with outcome and response to therapy, it is the proteins that do the work in the cell. At a functional level, derangements within the proteome, driven by post-translational and epigenetic modifications, such as phosphorylation, is the cause of a vast majority of human diseases. Cancer, for instance, is a manifestation of deranged cellular protein molecular networks and cell signaling pathways that are based on genetic changes at the DNA level. Importantly, the protein pathways contain the drug targets in signaling networks that govern overall cellular survival, proliferation, invasion and cell death. Consequently, the promise of proteomics resides in the ability to extend analysis beyond correlation to causality. A critical gap in the information knowledge base of molecular profiling is an understanding of the ongoing activity of protein signaling in human tissue: what is activated and “in use” within the human body at any given point in time. To address this gap, we have invented a new technology, called reverse phase protein microarrays, that can generate a functional read-out of cell signaling networks or pathways for an individual patient obtained directly from a biopsy specimen. This “wiring diagram” can serve as the basis for both, selection of a therapy and patient stratification.

Use of reverse phase protein microarrays and reference standard development for molecular network analysis of metastatic ovarian carcinoma

Cancer can be defined as a deregulation or hyperactivity in the ongoing network of intracellular and extracellular signaling events. Reverse phase protein microarray technology may offer a new opportunity to measure and profile these signaling pathways, providing data on post-translational phosphorylation events not obtainable by gene microarray analysis. Treatment of ovarian epithelial carcinoma almost always takes place in a metastatic setting since unfortunately the disease is often not detected until later stages. Thus, in addition to elucidation of the molecular network within a tumor specimen, critical questions are to what extent do signaling changes occur upon metastasis and are there common pathway elements that arise in the metastatic microenvironment. For individualized combinatorial therapy, ideal therapeutic selection based on proteomic mapping of phosphorylation end points may require evaluation of the patient's metastatic tissue. Extending these findings to the bedside will require the development of optimized protocols and reference standards. We have developed a reference standard based on a mixture of phosphorylated peptides to begin to address this challenge.

The Hofstedian approach : suggestions for a conceptual development of comparative journalism studies

In recent years there has been a burgeoning amount of research comparing journalistic practices in a wide range of countries around the world. Much of this literature has tended to focus on identifying what the similarities and differences between these different journalistic cultures are. Most importantly, research has focused on answering the question of whether, particularly in the age of globalisation, ‘a journalistic culture’ may exist. While there has been some evidence that there may indeed be a convergence of journalistic cultures, studies have at the same time found that important differences still persist. However, most of the literature has so far still tended to concentrate purely on the differences and similarities, without examining in detail why these exist. In this context, the author argues that employing a cross-cultural approach rooted in anthropology can at least partially trace the development of particularly the differences by linking them to the wider concept of cultural differences between countries. Specifically the paper here evaluates the usefulness of applying the value systems appraoch, as designed by Dutch anthropologist Geert Hofstede, to journalism research. By examining some of the few studies that have employed Hofstede’s approach, the paper argues that value systems can provide a classification on a conceptual level for investigating how journalism is practiced around the world. In the light of complaints in the Asia-Pacific region that the imported Western models of journalism are not in line with cultural values, this approach can also provide some basis from which to develop future approaches to journalism education.

Development and pilot study of the Primary Care Practice Improvement Tool (PC-PIT) : an innovative approach

Objective To assess the usability and validity of the Primary Care Practice Improvement Tool (PC-PIT), a practice performance improvement tool based on 13 key elements identified by a systematic review. It was co-created with a range of partners and designed specifically for primary health care. Design This pilot study examined the PC-PIT using a formative assessment framework and mixed-methods research design. Setting and participants Six high-functioning general practices in Queensland, Australia, between February and July 2013. A total of 28 staff participated — 10 general practitioners, six practice or community nurses, 12 administrators (four practice managers; one business manager and eight reception or general administrative staff). Main outcome measures Readability, content validity and staff perceptions of the PC-PIT. Results The PC-PIT offers an appropriate and acceptable approach to internal quality improvement in general practice. Quantitative assessment scores and qualitative data from all staff identified two areas in which the PC-PIT required modification: a reduction in the indicative reading age, and simplification of governance-related terms and concepts. Conclusion The PC-PIT provides an innovative approach to address the complexity of organisational improvement in general practice and primary health care. This initial validation will be used to develop a suite of supporting, high-quality and free-to-access resources to enhance the use of the PC-PIT in general practice. Based on these findings, a national trial is now underway.

Barriers to sustainable economic development : the Dallas–Fort Worth experience

This article examines the scope of existing economic development activity and the motivations and perceptions of practitioners to shed light on the barriers to sustainable practice. In contrast to related fields like urban planning, the economic development literature has minimally examined how practitioners think about sustainable development and the extent to which sustainable development principles are adopted in practice. This omission is significant because economic development policies can have a notable impact on the sustainable development goals of environmental protection and social equity alongside economic growth. To capture the extent to which economic developers engage in sustainable development and the barriers that practitioners face, we study fifteen cities in the Dallas–Fort Worth region. We find that six key barriers – a conventional economic development mindset, incentive-based practice, a lack of resources, ad hoc planning, inter-regional competition, and a lack of coordinated regional planning – impede sustainable economic development in the region.

Art spaces in community and economic development : connections to neighborhoods, artists, and the cultural economy

There is growing interest in the arts in community and economic development, yet little research examines the dynamics of community-based arts institutions to inform urban planning and policy. Drawing on interviews with participants and organizers of small and midsized art spaces, the study explores the factors that influence their involvement in neighborhood revitalization and outreach, support for artistic communities, and efforts to build bridges to commercial cultural sectors. Art spaces function as a conduit for building social networks that contribute to both community revitalization and artistic development. But issues pertaining to the location, organization, and management of art spaces may limit their community and economic development potential. The article concludes with proposals to craft stronger arts-based community and economic development programs.

Art spaces, public space, and the link to community development

Recent literature credits community art spaces with both enhancing social interaction and engagement and generating economic revitalization. This article argues that the ability of art spaces to realize these outcomes is linked to their role as public spaces and that their community development potential can be expanded with greater attention to this role. An analysis of the public space characteristics is useful because it encourages consideration of sometimes overlooked issues, particularly the effect of the physical environment on outcomes related to community development. I examine the relationship between public space and community development at various types of art spaces including artist cooperatives, ethnic-specific art spaces, and city-sponsored art centers in central city and suburban locations. This study shows that through their programming and other activities, art spaces serve various public space roles related to community development. However, the ability of many to perform as public spaces is hindered by facility design issues and poor physical connections in their surrounding area. This article concludes with proposals for enhancing the community development role of the art spaces through their function as public spaces.

Beyond Bilbao : rethinking flagship cultural development and planning in three California cities

Since the widely publicized revitalization success story of the Guggenheim Museum Bilbao, local governments have been scrambling to create their own flagship cultural projects. Because of the broad public sponsorship of such projects, urban planners need a full understanding of the associated potentials and problems. However, little research specifically examines the localized complexities of the flagship cultural strategy. Examining projects in Los Angeles, San Francisco, and San Jose, California, the article illustrates that much more than impressive architecture influences their catalytic ability. Flagship cultural projects are highly dependent on a variety of contextual factors and, therefore, should be positioned to build on existing arts and related commercial activity rather than gamble that they will generate new development from scratch.

Cultural development strategies and urban revitalization

Municipal governments around the globe increasingly turn to museums, performing arts centers, arts districts, and other cultural activities to promote and revitalize their cities. While a significant body of literature examines revitalization strategies that focus primarily around entertainment and commerce, the empirical body of research that specifically investigates the role of cultural strategies in urban redevelopment is still growing. This paper first discusses the development of municipal cultural strategies in the United States, and draws from the literature to outline the characteristics of three different models of such strategies. Second, the paper presents findings from a national survey distributed to municipal agencies involved in the promotion and development of cultural activities and facilities in large and medium‐sized US cities. The survey data indicate that although most agencies are guided by a varied set of goals, entrepreneurial objectives continue to guide the development and support of cultural activities in most cities.

BRAF inhibitor therapy for melanoma, thyroid and colorectal cancers : development of resistance and future prospects

BRAF is a major oncoprotein and oncogenic mutations in BRAF are found in a significant number of cancers, including melanoma, thyroid cancer, colorectal cancer and others. Consequently, BRAF inhibitors have been developed as treatment options for cancers with BRAF mutations which have shown some success in improving patient outcomes in clinical trials. Development of resistance to BRAF kinase inhibitors is common, however, and overcoming this resistance is an area of significant concern for clinicians, patients and researchers alike. In this review, we identify the mechanisms of BRAF kinase inhibitor resistance and discuss the implications for strategies to overcome this resistance in the context of new approaches such as multi-kinase targeted therapies and emerging RNA interference based technologies.

Development and evaluation of the Ontrack Diabetes Program : an automated, web-based type 2 diabetes self-management and dysphoria intervention

This research was conducted in the area of Clinical and Health Psychology. The study involved the development and evaluation of a novel, web-based program aimed to improve Type 2 diabetes self-management and mood. The program was developed as an original technological intervention aimed to improve access to support for rural and remote communities, and is currently being trialled across Australia with a larger sample size. The researcher aims to continue research into the field of clinical psychology, and in particular is interested in working on further interventions to support those with comorbid physical and mental health conditions.

Looking beyond image and tourism : the role of flagship cultural projects in local arts development

State and local governments frequently look to flagship cultural projects to improve the city image and catalyze tourism but, in the process, often overlook their potential to foster local arts development. To better understand this role, the article examines if and how cultural institutions in Los Angeles and San Francisco attract and support arts-related activity. The analysis reveals that cultural flagships have mixed success in generating arts-based development and that their ability may be improved through attention to the local context, facility and institutional characteristics, and the approach of the sponsoring agencies. Such knowledge is useful for planners to enhance their revitalization efforts, particularly as the economic development potential of arts organizations and artists has become more apparent.

Museums as urban catalysts : the role of urban design in flagship cultural development

A long-held urban redevelopment strategy has been the investment in flagship cultural projects—large-scale, iconic museums and arts centres that are intended to enhance the city image while catalyzing private sector investment and attracting tourists to the surrounding area. This paper concentrates on an aspect of the flagship cultural strategy that has received surprisingly little focused attention—the role that urban design and context play in realizing project outcomes. The analysis concentrates on two established flagship museums in Los Angeles and San Jose, California. The research demonstrates that certain urban design characteristics can negatively affect the ability of a project to attract visitors and generate commercial activity. However, at the same time, factors beyond the local context may be an overriding factor in project outcomes thus calling into question the concept of cultural catalyst.

Development of gas sensing technology for ground and airborne applications powered by solar energy : methodology and experimental results

Monitoring gases for environmental, industrial and agricultural fields is a demanding task that requires long periods of observation, large quantity of sensors, data management, high temporal and spatial resolution, long term stability, recalibration procedures, computational resources, and energy availability. Wireless Sensor Networks (WSNs) and Unmanned Aerial Vehicles (UAVs) are currently representing the best alternative to monitor large, remote, and difficult access areas, as these technologies have the possibility of carrying specialised gas sensing systems, and offer the possibility of geo-located and time stamp samples. However, these technologies are not fully functional for scientific and commercial applications as their development and availability is limited by a number of factors: the cost of sensors required to cover large areas, their stability over long periods, their power consumption, and the weight of the system to be used on small UAVs. Energy availability is a serious challenge when WSN are deployed in remote areas with difficult access to the grid, while small UAVs are limited by the energy in their reservoir tank or batteries. Another important challenge is the management of data produced by the sensor nodes, requiring large amount of resources to be stored, analysed and displayed after long periods of operation. In response to these challenges, this research proposes the following solutions aiming to improve the availability and development of these technologies for gas sensing monitoring: first, the integration of WSNs and UAVs for environmental gas sensing in order to monitor large volumes at ground and aerial levels with a minimum of sensor nodes for an effective 3D monitoring; second, the use of solar energy as a main power source to allow continuous monitoring; and lastly, the creation of a data management platform to store, analyse and share the information with operators and external users. The principal outcomes of this research are the creation of a gas sensing system suitable for monitoring any kind of gas, which has been installed and tested on CH4 and CO2 in a sensor network (WSN) and on a UAV. The use of the same gas sensing system in a WSN and a UAV reduces significantly the complexity and cost of the application as it allows: a) the standardisation of the signal acquisition and data processing, thereby reducing the required computational resources; b) the standardisation of calibration and operational procedures, reducing systematic errors and complexity; c) the reduction of the weight and energy consumption, leading to an improved power management and weight balance in the case of UAVs; d) the simplification of the sensor node architecture, which is easily replicated in all the nodes. I evaluated two different sensor modules by laboratory, bench, and field tests: a non-dispersive infrared module (NDIR) and a metal-oxide resistive nano-sensor module (MOX nano-sensor). The tests revealed advantages and disadvantages of the two modules when used for static nodes at the ground level and mobile nodes on-board a UAV. Commercial NDIR modules for CO2 have been successfully tested and evaluated in the WSN and on board of the UAV. Their advantage is the precision and stability, but their application is limited to a few gases. The advantages of the MOX nano-sensors are the small size, low weight, low power consumption and their sensitivity to a broad range of gases. However, selectivity is still a concern that needs to be addressed with further studies. An electronic board to interface sensors in a large range of resistivity was successfully designed, created and adapted to operate on ground nodes and on-board UAV. The WSN and UAV created were powered with solar energy in order to facilitate outdoor deployment, data collection and continuous monitoring over large and remote volumes. The gas sensing, solar power, transmission and data management systems of the WSN and UAV were fully evaluated by laboratory, bench and field testing. The methodology created to design, developed, integrate and test these systems was extensively described and experimentally validated. The sampling and transmission capabilities of the WSN and UAV were successfully tested in an emulated mission involving the detection and measurement of CO2 concentrations in a field coming from a contaminant source; the data collected during the mission was transmitted in real time to a central node for data analysis and 3D mapping of the target gas. The major outcome of this research is the accomplishment of the first flight mission, never reported before in the literature, of a solar powered UAV equipped with a CO2 sensing system in conjunction with a network of ground sensor nodes for an effective 3D monitoring of the target gas. A data management platform was created using an external internet server, which manages, stores, and shares the data collected in two web pages, showing statistics and static graph images for internal and external users as requested. The system was bench tested with real data produced by the sensor nodes and the architecture of the platform was widely described and illustrated in order to provide guidance and support on how to replicate the system. In conclusion, the overall results of the project provide guidance on how to create a gas sensing system integrating WSNs and UAVs, how to power the system with solar energy and manage the data produced by the sensor nodes. This system can be used in a wide range of outdoor applications, especially in agriculture, bushfires, mining studies, zoology, and botanical studies opening the way to an ubiquitous low cost environmental monitoring, which may help to decrease our carbon footprint and to improve the health of the planet.

Training needs research applied to the development of a standardised incident investigator training framework

In response to the rail industry lacking a consistently accepted standard of minimal training to perform incident investigations, the Australasian rail industry requested the development of a unified approach to investigator training. This paper details how the findings from a training needs analysis were applied to inform the development of a standardised training package for rail incident investigators. Data from job descriptions, training documents and subject matter experts sourced from 17 Australasian organisations were analysed and refined to yield a draft set of 10 critical competencies. Finally the draft of critical competencies was reviewed by industry experts to verify the accuracy and completeness of the competency list and to consider the most appropriate level of qualification for training development. The competencies identified and the processes described to translate research into an applied training framework in this paper, can be generalised to assist practitioners and researchers in developing industry approved standardised training packages.