Ryanodine receptor phosphorylation in human heart failure

Heart failure is a complex disorder, characterized by activation of the sympathetic nervous system, leading to dysregulated Ca2+ homeostasis in cardiac myocytes and tissue remodeling. In a variety of diseases, cardiac malfunction is associated with aberrant fluxes of Ca2+ across both the surface membrane and the internal Ca2+ store, the sarcoplasmic reticulum (SR). One prominent hypothesis residues is that in heart failure, the activity of the ryanodine receptor (RyR2) Ca2+ release channel in the SR is increased due to excess phosphorylation and that this contributes to excess SR Ca2+ leak in diastole, reduced SR Ca2+ load and decreased contractility (Huke & Bers, 2008). There is controversy over which serine residues in RyR2 are hyperphosphorylated in animal models of heart failure and whether this is via the CaMKII or the PKA-linked signaling pathway. S2808, S2814 and S2030 in RyR2 have been variously claimed to be hyperphosphorylated. Our aim was to examine the degree of phosphorylation of these residues in RyR2 from failing human hearts. The use of human tissue was approved by the Human Research Ethics Committee, The Prince Charles Hospital, EC28114. Left ventricular tissue samples were obtained from an explanted heart of a patient with endstage heart failure (Emery Dreifuss Muscular Dystrophy with cardiomyopathy) and non-failing tissue was from a patient with cystic fibrosis undergoing heart-lung transplantation with no history of heart disease. SR vesicles were prepared as described by Laver et al. (1995) and examined with SDS-Page and Western Blot. Transferred proteins were probed with antibodies to detect total protein phosphorylation, phosphorylation of RyR2 serine residues S2808, S2814, S2030 and for the key proteins calsequestrin, triadin, junctin and FKBP12.6. To avoid membrane stripping artifact, each membrane was exposed to one phosphorylation-specific antibody and signal densities quantified using Bio-Rad Quantity One software. We found no distinguishable difference between failing and healthy hearts in the protein expression levels of RyR2, triadin, junctin or calsequestrin. We found an expected upregulation of total RyR2 phosphorylation in the failing heart sample, compared to a matched amount of RyR2 (quantified using densiometry) in healthy heart. Probing with antibodies detecting only the phosphorylated form of the specific RyR2 residues showed that the increase in total RyR2 phosphorylation in the failing heart was due to hyperphosphorylation of S2808 and S2814. We found that S2030 phosphorylation levels were unchanged in human heart failure. Interestingly, we found that S2030 has a basal level of phosphorylation in the healthy human heart, different from the absence of basal phosphorylation recently reported in rodent heart (Huke & Bers, 2008). Finally, preliminary results indicate that less FKBP 12.6 is associated with RyR2 in the failing heart, possibly as a consequence of PKA activation. In conclusion, residues S2808 and S2814 are hyperphosphorylated in human heart failure, presumably due to upregulation of the CaMKII and/or PKA signaling pathway as a result of chronic activation of the sympathetic nervous system. Such changes in RyR2 phosphorylation are believed to contribute to the leaky RyR2 phenotype associated with heart failure, which increases the incidence of arrhythmia and contributes to the severely impaired contractile performance of the failing heart. Huke S & Bers DM. (2008). Ryanodine receptor phosphorylation at serine 2030, 2808 and 2814 in rat cardiomyocytes. Biochemical and Biophysical Research Communications 376, 80-85. Laver DR, Roden LD, Ahern GP, Eager KR, Junankar PR & Dulhunty AF. (1995). Cytoplasmic Ca2+ inhibits the ryanodine receptor from cardiac muscle. Journal of Membrane Biology 147, 7-22. Proceedings

Creating global networks through an online engineering graduate program

Internationally the railway industry is facing a severe shortage of engineers with high level, relevant, profession and technical knowledge and abilities, in particular amongst engineers involved in the design, construction and maintenance of railway infrastructure. A unique graduate level program has been created to meet that global need via a fully online, distance education format. The development and operation of this Master of Engineering degree is proposed as a model of the process needed for the industry-relevance, flexible delivery, international networking, and professional development required for a successful graduate engineering program in the 21st century. In particular, the paper demonstrates how a mix of new and more familiar technologies are utilised through a variety of tasks to overcome the huge distances and multiple time zones that separate the participants across a growing number of countries, successfully achieving close and sustained interaction amongst the participants and railway experts.

Leg Clubs® : a clinically and cost-effective approach to lower limb management

Leg ulcers affect 55000-90000 people, predominantly aged over 65, in the UK at any one time. Traditional care, delivered in people’s homes by district nurses or in GP clinics, is costly and often not effective, with slow healing rates and a high incidence of recurrence. A social model of leg ulcer clinics developed by the author has been shown to improve healing and reduce recurrence within a highly cost-effective framework that delivers genuine patient empowerment, public health education and social outreach. This paper outlines the rationale for the Leg Club, its clinical and social impact, and the infrastructure behind it. It also considers the challenges to establishing and running a Leg Club.

A kiss is just...

This paper proposes that a survey of representations of men not-kissing men in recent television drama series makes clear a particularly hysterical fascination. While the Australian program GP has managed to produce a banal representation of two men kissing, American equivalents have resorted to a series of strategies which make insistently clear that not only can men not kiss-but that the act of not-kissing must be repeatedly displayed. By refusing to have lovers kiss; by having lovers kiss but refusing to show the act; by having gay lovers, but having one played by a woman; by having men kiss but rendering the act ridiculous; in these ways, American television programs make clear the importance of this act by consistently pointing towards it and declaring its impossibility. This paper calls for the justice of equal access to public images of kissing.

Getting to know a stranger-rural nurses' experiences of mentoring : a grounded theory

Background: Mentoring is often proposed as a solution to the problem of successfully recruiting and retaining nursing staff. The aim of this constructivist grounded theory study was to explore Australian rural nurses' experiences of mentoring. Design: The research design used was reflexive in nature resulting in a substantive, constructivist grounded theory study. Participants: A national advertising campaign and snowball sampling were used to recruit nine participants from across Australia. Participants were rural nurses who had experience in mentoring others. Methods: Standard grounded theory methods of theoretical sampling, concurrent data collection and analysis using open, axial and theoretical coding and a story line technique to develop the core category and category saturation were used. To cultivate the reflexivity required of a constructivist study, we also incorporated reflective memoing, situational analysis mapping techniques and frame analysis. Data was generated through eleven interviews, email dialogue and shared situational mapping. Results: Cultivating and growing new or novice rural nurses using supportive relationships such as mentoring was found to be an existing, integral part of experienced rural nurses' practice, motivated by living and working in the same communities. Getting to know a stranger is the first part of the process of cultivating and growing another. New or novice rural nurses gain the attention of experienced rural nurses through showing potential or experiencing a critical incidence. Conclusions: The problem of retaining nurses is a global issue. Experienced nurses engaged in clinical practice have the potential to cultivate and grow new or novice nurses-many already do so. Recognising this role and providing opportunities for development will help grow a positive, supportive work environment that nurtures the experienced nurses of tomorrow.

Work integrated learning for life : encouraging agentic engagement

In a rapidly changing world where new work patterns impact on our health, relationships and social fabric, it is critical that we reconsider the role universities could or should play in helping students prepare for the complexities of the 21st century. Efforts to respond to economic imperatives such as the skills shortage have seen a rush to embed work integrated and career development learning in the curriculum as well as a strengthening of the discourse that the university’s role is primarily to produce industry ready or ‘oven ready and self basting’ graduates (Atkins, 1999). This narrow focus on ‘giving industry what industry wants’ (Patrick, Peach & Pocknee, 2009) ignores the importance of helping students develop the types of skills and dispositions they will need. To enable students to thrive not just survive socially and economically in a radically unknowable world, where knowledge becomes obsolete, we need to be ready to develop new futures (Barnett, 2004). This paper considers the concept of ‘work’, the role it plays in our lives, and our aspirations to build sustainable, socially connected communities. We revisit the assumptions underlying the employability argument (Atkins, 1999) in the light of changing notions of work (Hagel, Seely Brown & Davison, 2010), and the need for higher education to contribute to a better and more sustainable society (Pocock, 2003). Specifically we present initiatives developed from work integrated learning (WIL) programs in the United Kingdom and Australia, where WIL programs are framed within the broader context of real world and life-wide curriculum (Jackson, 2010), and where transferable skills and elements of work-related learning programs prepare students for less certain job futures. Such approaches encourage students to take an agentic role (Billett & Pavlova, 2005) in selecting their work possibilities to develop resilience and capabilities to deal with new and challenging situations, assisting students to become who they want to be not just what they want to be. The theoretical and operational implications and challenges of shaping real world and life-wide curriculum will be investigated in more depth in the next phase of this research.

Evolving noisy oscillatory dynamics in genetic regulatory networks

We introduce a genetic programming (GP) approach for evolving genetic networks that demonstrate desired dynamics when simulated as a discrete stochastic process. Our representation of genetic networks is based on a biochemical reaction model including key elements such as transcription, translation and post-translational modifications. The stochastic, reaction-based GP system is similar but not identical with algorithmic chemistries. We evolved genetic networks with noisy oscillatory dynamics. The results show the practicality of evolving particular dynamics in gene regulatory networks when modelled with intrinsic noise.

The development of a program to assist international nursing students to be prepared for clinical practice in the Australian health care context

Health education in Western Countries has grown considerably in the last decade and this has occurred for a number of reasons. Specifically Universities actively recruit International students as the health workforce becomes global; also it is much easier for students to move and study globally. Internationally there is a health workforce shortage and if students gain a degree in a reputable university their ability to work globally is improved significantly. However, when studying to practice in the health care field the student must undertake clinical practice in an acute or aged care setting. This can be a significant problem for students who are culturally and linguistically diverse in an English speaking country such as Australia. The issues that can arise stem from the language differences where communication, interpretation understanding and reading the cultural norms of the health care setting are major challenges for International students. To assist international students to be successful in their clinical education, an extra curriculum workshop program was developed to provide additional support. The program which runs twice each year includes on-campus interactive workshops that are complemented by targeted support provided for students and clinical staff who are supervising students’ practice experience in the workplace. As this is an English speaking country the workshop is based on practicing reading, writing, listening and speaking, as well as exploring basic health care concepts and cultural differences. This enables students to gain knowledge of and practice interpretation of cultural norms and expectations in a safe environment. This innovative series of interactive workshops in a highly student-centred learning environment combine education with role play and discussion with peers who are supported by culturally aware and competent Educators. Over the years it has been running, the program has been undertaken by an increasing number of students. In 2011, more than 100 students are expected to participate. Student evaluation of the program has confirmed that it has assisted the majority of them to be successful in their clinical studies. Effectiveness of the project is measured throughout the program and in follow up sessions. This ongoing information allows for continuous development of the program that serves to meet individual needs of the International student, the University and Service providers such as the hospitals. This feedback from students regarding their increased comprehension of the Australian colloquial Language, healthcare terminology, critical thinking and clinical skill development and a cultural awareness also enables them to maintain their feelings of self confidence and self esteem.

Motivations, expectations and experiences of Australian rural and regional planners

Despite playing an extremely important role in shaping communities, the role and contribution of planners is not widely understood or acknowledged. At the same time, there is a shortage of planners in Australia, especially in non-urban areas. Thus, though an online survey of 185 rural and regional planners, this research explores their motivations, expectations and experiences. Most enjoyed and felt confident in their role, explaining that they valued the relaxed family orientated rural lifestyle and the varied nature of the planning work. Although they sometimes felt isolated, the non-urban location provided quicker progression to senior roles, the ability to engage directly with the community and to see the consequences of their decisions. Only half felt their education had prepared them well for their role, citing gaps in terms of computerised modelling, team leadership and conflict resolution skills. Their feedback centred on providing a more practical course, focussing more on regional planning, and encouraging urban and rural experience placements. As the first study to quantifiably explore rural and regional Australian planners perceptions of their role and challenges, the findings illustrate current experiences, key planning challenges, perceived educational gaps and future priorities.

Converting theory to practice : university-school collaboration on devising strategies for mentoring pedagogical knowledge

There appears no shortage of theorists for preservice teacher education; however many ideas are abandoned without practical applications. Indeed, it can take years for theories to materialise into practice, if they materialise at all. The quality of preservice teacher education is central for enhancing an education system, and mentors’ roles can assist to shape preservice teachers’ development within the school context. Yet mentoring can be haphazard without being underpinned by a theoretical framework. A mentoring model (personal attributes, system requirements, pedagogical knowledge, modelling, and feedback) has emerged from research and the literature to guide mentors’ practices. This qualitative study investigates mentors’ pedagogical knowledge as one factor crucial to the mentoring process. More specifically, this study involves a questionnaire and audio-recorded focus group meetings with experienced mentors (n=14) who deliberated on devising practical applications for mentoring pedagogical knowledge. Findings revealed that these experienced mentors pinpointed practical applications around a mentor’s role for providing pedagogical knowledge to the mentee. These strategies were varied and demonstrated that any one mentoring practice may be approached from a number of different angles. Nevertheless, there were core mentoring practices in pedagogical knowledge such as showing the mentee how to plan for teaching, articulating classroom management approaches, and talking about how to connect learning to assessment. Mentors may require education on current mentoring practices with practical strategies that are linked to theoretical underpinnings.

Why do nurses migrate? – a review of recent literature

Aim  To identify the reasons why nurses continue migrating across international borders. Background  International nurse recruitment and migration have been increasing in the last decade and recent trends show an increase in the movement of nurses between developing and developed countries, resulting in a worldwide shortage of nurses. Methods  A manual and electronic database literature search was conducted from January 2004 to May 2010. Qualitative content analysis was completed for the final 17 articles that satisfied the inclusion criteria. Results  Motivators to nurse migration were linked to financial, professional, political, social and personal factors. Although economic factors were the most commonly reported, they were not the only reason for migration. This was especially evident among nurses migrating between developed countries. Conclusion  Nurses migrate for a wide variety of reasons as they respond to push and pull factors. Implications for nursing management  It is important for nurse managers in the source countries to advocate incentives to retain nurses. In the recipient countries the number of international nurses continues to increase implying the need for more innovative ways to mentor and orientate these nurses.

An analysis of NSW rural property market : 1990-2010

Rural property in Australia has seen significant market resurgence over the past 3 years, with improved seasonal conditions in a number of states, improved commodity prices and a greater interest and purchase of rural land by major international corporations and investment institutions. Much of this change in perspective in relation to rural property as an asset class can be linked to the food shortage of 2007 and the subsequent interest by many countries in respect to food security. This paper will address the total and capital return performance of a major agricultural area and compare these returns on the basis of both location of land and land use. The comparison will be used to determine if location or actual land use has a greater influence on rural property capital and income returns. This performance analysis is based on over 40,000 rural sales transactions. These transactions cover all market based rural property transactions in New South Wales, Australia for the period January 1990 to December 2010. Correlation analysis and investment performance analysis has also been carried out to determine the possible relationships between location and land use and subsequent changes in rural land capital values.

Where not to have a Heart Attack in Australia!: The Cardiac ARIA Index

Background/aims: Access to appropriate health care following an acute cardiac event is important for positive outcomes. The aim of the Cardiac ARIA index was to derive an objective, comparable, geographic measure reflecting access to cardiac services across Australia. Methods: Geographic Information Systems (GIS) were used to model a numeric-alpha index based on acute management from onset of symptoms to return to the community. Acute time frames have been calculated to include time for ambulance to arrive, assess and load patient, and travel to facility by road 40–80 kph. Results: The acute phase of the index was modelled into five categories: 1 [24/7 percutaneous cardiac intervention (PCI) ≤1 h]; 2 [24/7 PCI 1–3 h, and PCI less than an additional hour to nearest accident and emergency room (A&E)]: 3 [Nearest A&E ≤3 h (no 24/7 PCI within an extra hour)]: 4 [Nearest A&E 3–12 h (no 24/7 PCI within an extra hour)]: 5 [Nearest A&E 12–24 h (no 24/7 PCI within an extra hour)]. Discharge care was modelled into three categories based on time to a cardiac rehabilitation program, retail pharmacy, pathology services, hospital, GP or remote clinic: (A) all services ≤30 min; (B) >30 min and ≤60 min; (C) >60 min. Examples of the index indicate that the majority of population locations within capital cities were category 1A; Alice Springs and Byron Bay were 3A; and the Northern Territory town of Maningrida had minimal access to cardiac services with an index ranking of 5C. Conclusion: The Cardiac ARIA index provides an invaluable tool to inform appropriate strategies for the use of scarce cardiac resources.

Getting stuck in together : improving work integrated learning from an Australian institution and faculty perspective

According to a recent report Australian higher education is not in crisis. However, we could be doing it better. The report Mapping Australian Higher Education (Norton, 2012) highlights comparative weaknesses such as levels f student engagement; interactions between students and academic staff; and academic staff preferences for research over teaching. The report points out that despite these concerns most graduates continue to get good, well-paid jobs, student satisfaction is improving, and levels of public confidence in Australian higher education are high. It also stresses that ‘the promise of higher education is that it provides adaptable cognitive skills, not that it always provides the job specific skills graduates will need in their future employment’ (Norton, 2012, p.58). This is worth keeping in mind as we contribute to the significant growth in curriculum initiatives aimed at preparing graduates for the world of work. Work Integrated Learning (WIL) is not a new concept but there is increased pressure on higher education globally to address graduate employability skills. The sector is under pressure in an increasingly competitive environment to demonstrate the relevance of courses, accountability and effective use of public funds (Peach & Gamble, 2011). In the Australian context this also means responding to the skills shortage in areas such as engineering, health, construction and business (DEEWR, 2010). This paper provides a brief overview of collaborative efforts over several years to improve the activity of WIL at the Queensland University of Technology (QUT). These efforts have resulted in changes to curriculum, pedagogy, systems and processes, and the initiation of local, regional, national, and international networks. The willingness of students, staff, and industry partners to ‘get stuck in’ and try new approaches in these different contexts can be understood as a form of boundary spanning. That is, the development of the capability to mediate between different forms of expertise and the demands of different contexts in order to nurture student learning and improve the outcomes of higher education through WIL (Peach, Cates, Ilg, Jones, Lechleiter, 2011).