Biochemical characterization of Aprataxin, the protein deficient in Ataxia with Oculomotor Apraxia type 1

Neurodegenerative disorders are heterogenous in nature and include a range of ataxias with oculomotor apraxia, which are characterised by a wide variety of neurological and ophthalmological features. This family includes recessive and dominant disorders. A subfamily of autosomal recessive cerebellar ataxias are characterised by defects in the cellular response to DNA damage. These include the well characterised disorders Ataxia-Telangiectasia (A-T) and Ataxia-Telangiectasia Like Disorder (A-TLD) as well as the recently identified diseases Spinocerebellar ataxia with axonal neuropathy Type 1 (SCAN1), Ataxia with Oculomotor Apraxia Type 2 (AOA2), as well as the subject of this thesis, Ataxia with Oculomotor Apraxia Type 1 (AOA1). AOA1 is caused by mutations in the APTX gene, which is located at chromosomal locus 9p13. This gene codes for the 342 amino acid protein Aprataxin. Mutations in APTX cause destabilization of Aprataxin, thus AOA1 is a result of Aprataxin deficiency. Aprataxin has three functional domains, an N-terminal Forkhead Associated (FHA) phosphoprotein interaction domain, a central Histidine Triad (HIT) nucleotide hydrolase domain and a C-terminal C2H2 zinc finger. Aprataxins FHA domain has homology to FHA domain of the DNA repair protein 5’ polynucleotide kinase 3’ phosphatase (PNKP). PNKP interacts with a range of DNA repair proteins via its FHA domain and plays a critical role in processing damaged DNA termini. The presence of this domain with a nucleotide hydrolase domain and a DNA binding motif implicated that Aprataxin may be involved in DNA repair and that AOA1 may be caused by a DNA repair deficit. This was substantiated by the interaction of Aprataxin with proteins involved in the repair of both single and double strand DNA breaks (XRay Cross-Complementing 1, XRCC4 and Poly-ADP Ribose Polymerase-1) and the hypersensitivity of AOA1 patient cell lines to single and double strand break inducing agents. At the commencement of this study little was known about the in vitro and in vivo properties of Aprataxin. Initially this study focused on generation of recombinant Aprataxin proteins to facilitate examination of the in vitro properties of Aprataxin. Using recombinant Aprataxin proteins I found that Aprataxin binds to double stranded DNA. Consistent with a role for Aprataxin as a DNA repair enzyme, this binding is not sequence specific. I also report that the HIT domain of Aprataxin hydrolyses adenosine derivatives and interestingly found that this activity is competitively inhibited by DNA. This provided initial evidence that DNA binds to the HIT domain of Aprataxin. The interaction of DNA with the nucleotide hydrolase domain of Aprataxin provided initial evidence that Aprataxin may be a DNA-processing factor. Following these studies, Aprataxin was found to hydrolyse 5’adenylated DNA, which can be generated by unscheduled ligation at DNA breaks with non-standard termini. I found that cell extracts from AOA1 patients do not have DNA-adenylate hydrolase activity indicating that Aprataxin is the only DNA-adenylate hydrolase in mammalian cells. I further characterised this activity by examining the contribution of the zinc finger and FHA domains to DNA-adenylate hydrolysis by the HIT domain. I found that deletion of the zinc finger ablated the activity of the HIT domain against adenylated DNA, indicating that the zinc finger may be required for the formation of a stable enzyme-substrate complex. Deletion of the FHA domain stimulated DNA-adenylate hydrolysis, which indicated that the activity of the HIT domain may be regulated by the FHA domain. Given that the FHA domain is involved in protein-protein interactions I propose that the activity of Aprataxins HIT domain may be regulated by proteins which interact with its FHA domain. We examined this possibility by measuring the DNA-adenylate hydrolase activity of extracts from cells deficient for the Aprataxin-interacting DNA repair proteins XRCC1 and PARP-1. XRCC1 deficiency did not affect Aprataxin activity but I found that Aprataxin is destabilized in the absence of PARP-1, resulting in a deficiency of DNA-adenylate hydrolase activity in PARP-1 knockout cells. This implies a critical role for PARP-1 in the stabilization of Aprataxin. Conversely I found that PARP-1 is destabilized in the absence of Aprataxin. PARP-1 is a central player in a number of DNA repair mechanisms and this implies that not only do AOA1 cells lack Aprataxin, they may also have defects in PARP-1 dependant cellular functions. Based on this I identified a defect in a PARP-1 dependant DNA repair mechanism in AOA1 cells. Additionally, I identified elevated levels of oxidized DNA in AOA1 cells, which is indicative of a defect in Base Excision Repair (BER). I attribute this to the reduced level of the BER protein Apurinic Endonuclease 1 (APE1) I identified in Aprataxin deficient cells. This study has identified and characterised multiple DNA repair defects in AOA1 cells, indicating that Aprataxin deficiency has far-reaching cellular consequences. Consistent with the literature, I show that Aprataxin is a nuclear protein with nucleoplasmic and nucleolar distribution. Previous studies have shown that Aprataxin interacts with the nucleolar rRNA processing factor nucleolin and that AOA1 cells appear to have a mild defect in rRNA synthesis. Given the nucleolar localization of Aprataxin I examined the protein-protein interactions of Aprataxin and found that Aprataxin interacts with a number of rRNA transcription and processing factors. Based on this and the nucleolar localization of Aprataxin I proposed that Aprataxin may have an alternative role in the nucleolus. I therefore examined the transcriptional activity of Aprataxin deficient cells using nucleotide analogue incorporation. I found that AOA1 cells do not display a defect in basal levels of RNA synthesis, however they display defective transcriptional responses to DNA damage. In summary, this thesis demonstrates that Aprataxin is a DNA repair enzyme responsible for the repair of adenylated DNA termini and that it is required for stabilization of at least two other DNA repair proteins. Thus not only do AOA1 cells have no Aprataxin protein or activity, they have additional deficiencies in PolyADP Ribose Polymerase-1 and Apurinic Endonuclease 1 dependant DNA repair mechanisms. I additionally demonstrate DNA-damage inducible transcriptional defects in AOA1 cells, indicating that Aprataxin deficiency confers a broad range of cellular defects and highlighting the complexity of the cellular response to DNA damage and the multiple defects which result from Aprataxin deficiency. My detailed characterization of the cellular consequences of Aprataxin deficiency provides an important contribution to our understanding of interlinking DNA repair processes.

The effectiveness of using a simple ARIA based geographical classification to identify road crash patterns in rural and urban areas of Queensland

Research has noted a ‘pronounced pattern of increase with increasing remoteness' of death rates in road crashes. However, crash characteristics by remoteness are not commonly or consistently reported, with definitions of rural and urban often relying on proxy representations such as prevailing speed limit. The current paper seeks to evaluate the efficacy of the Accessibility / Remoteness Index of Australia (ARIA+) to identifying trends in road crashes. ARIA+ does not rely on road-specific measures and uses distances to populated centres to attribute a score to an area, which can in turn be grouped into 5 classifications of increasing remoteness. The current paper uses applications of these classifications at the broad level of Australian Bureau of Statistics' Statistical Local Areas, thus avoiding precise crash locating or dedicated mapping software. Analyses used Queensland road crash database details for all 31,346 crashes resulting in a fatality or hospitalisation occurring between 1st July, 2001 and 30th June 2006 inclusive. Results showed that this simplified application of ARIA+ aligned with previous definitions such as speed limit, while also providing further delineation. Differences in crash contributing factors were noted with increasing remoteness such as a greater representation of alcohol and ‘excessive speed for circumstances.' Other factors such as the predominance of younger drivers in crashes differed little by remoteness classification. The results are discussed in terms of the utility of remoteness as a graduated rather than binary (rural/urban) construct and the potential for combining ARIA crash data with census and hospital datasets.

National consumer credit laws, financial exclusion and interest rate caps : The case for diversity within a centralised framework

Australia is going through a major reform of consumer credit regulation, with the implementation of a proposal to transfer regulatory responsibility from the State and Territory Governments to the Commonwealth Government. While the broad policy approach is supported, the reform process has missed a significant opportunity to engage directly with issues of financial exclusion and with the potential role of regulation to reduce financial exclusion. The imposition of an interest rate cap can limit the impact of financial exclusion. However, the future of the existing interest rate caps is uncertain, given the diversity of approaches, and the heated debate that surrounds this issue. In the absence of support for regulatory initiatives to increase the availability of low cost, small loans, permitting regulatory diversity on this issue of interest rate caps, within an otherwise centralised regulatory framework., can minimise the impact of financial exclusion on consumers.

New routes for the field trip

As with the broader field of education research, most writing on the subject of school excursions and field trips has centred around progressive/humanist concerns for building pupil’s self-esteem and for the development of the ‘whole child’. Such research has also stressed the importance of a broad, grounded, and experiential curriculum - as exemplified by subjects containing these extra-school activities - as well as the possibility of strengthening the relationship between student and teacher. Arguing that this approach to the field trip is both exhausted of ideas and conceptually flawed, this paper proposes some alternate routes into the area for the prospective researcher. First, it is argued that by historicising the subject matter, it can be seen that school excursions are not simply the product of the contemporary humanist desire for diverse and fulfilling educational experiences, rather they can, in part, be traced to eighteenth century beliefs among the English gentry that travel formed a crucial component of a good education, to the advent of an affordable public rail system, and to school tours associated with the Temperance movement. Second, field trips can be understood from within the associated framework of concerns over the governance of tourism and the organisation of disciplinary apparatuses for the production of an educated and regulated citizenry. Far from being a simple learning experience, museums and art galleries form part of a complex of disciplinary and power relations designed to produce a populace with very specific capacities, aspirations and styles of public conduct. Finally, rather than allowing children ‘freedom’ from the constraints of the classroom, on the contrary, through the medium of the field-trip, children can become accustomed to having their activities governed in the broader domain of the generalised community . School excursions thereby constitute an effective tactic through which young people have their conduct managed, and their social and scholastic identities shaped and administered.

Real estate agency practice and profitability : an analysis of house sales and agency profitability in Sydney

Large cities provide a broad range of residential property types, as well as a range of socio-economic locations. This results in a significant variation in residential property prices across both the city itself and the individual suburbs. The only constant across such a diverse range of residential property is the need for the majority of residential property owners to employ the services of a real estate agent to sell their property or to purchase a residential property. This paper will analyse the Sydney residential property market over the period 1994 to 2002 to determine the change in real estate offices numbers over the period, the profitability of real estate agency offices based on the residential house price performance of houses and units in these specific locations and the extent of changing residential house prices on agency profitability. Suburbs have been selected to provide a full range of housing types, socio-economic areas, older established and developing residential suburbs and location from the

Designing for engagement : building IT systems

Context The School of Information Technology at QUT has recently undertaken a major restructuring of their Bachelor of Information Technology (BIT) course. Some of the aims of this restructuring include a reduction in first year attrition and to provide an attractive degree course that meets both student and industry expectations. Emphasis has been placed on the first semester in the context of retaining students by introducing a set of four units that complement one another and provide introductory material on technology, programming and related skills, and generic skills that will aid the students throughout their undergraduate course and in their careers. This discussion relates to one of these four fist semester units, namely Building IT Systems. The aim of this unit is to create small Information Technology (IT) systems that use programming or scripting, databases as either standalone applications or web applications. In the prior history of teaching introductory computer programming at QUT, programming has been taught as a stand alone subject and integration of computer applications with other systems such as databases and networks was not undertaken until students had been given a thorough grounding in those topics as well. Feedback has indicated that students do not believe that working with a database requires programming skills. In fact, the teaching of the building blocks of computer applications have been compartmentalized and taught in isolation from each other. The teaching of introductory computer programming has been an industry requirement of IT degree courses as many jobs require at least some knowledge of the topic. Yet, computer programming is not a skill that all students have equal capabilities of learning (Bruce et al., 2004) and this is clearly shown by the volume of publications dedicated to this topic in the literature over a broad period of time (Eckerdal & Berglund, 2005; Mayer, 1981; Winslow, 1996). The teaching of this introductory material has been done pretty much the same way over the past thirty years. During this period of time that introductory computer programming courses have been taught at QUT, a number of different programming languages and programming paradigms have been used and different approaches to teaching and learning have been attempted in an effort to find the golden thread that would allow students to learn this complex topic. Unfortunately, computer programming is not a skill that can be learnt in one semester. Some basics can be learnt but it can take many years to master (Norvig, 2001). Faculty data typically has shown a bimodal distribution of results for students undertaking introductory programming courses with a high proportion of students receiving a high mark and a high proportion of students receiving a low or failing mark. This indicates that there are students who understand and excel with the introductory material while there is another group who struggle to understand the concepts and practices required to be able to translate a specification or problem statement into a computer program that achieves what is being requested. The consequence of a large group of students failing the introductory programming course has been a high level of attrition amongst first year students. This attrition level does not provide good continuity in student numbers in later years of the degree program and the current approach is not seen as sustainable.

An analysis and comparison of rural land sales

Rural land prices, in developed, free trade real estate markets, are influenced not only by prevailing economic conditions but also physical factors such as climate, topography and soil type. In broad acre farming and grazing operations, both commodity price and yields determine farm income. Yields, in turn, are a function of climate, topography and soil type. The strength of a rural land market is influenced by the overall rural economy in a Country, State or region. These differences in rural land markets can also vary within smaller regions. It has been held that rural land, in relative safe production areas, is less effected by adverse economic and climatic factors than land in more marginal agricultural areas. This paper will analyse rural land sales in both traditional cropping areas and marginal cropping areas for the period 1975 to 1996. The analysis will determine the overall trend in rural land prices over the period, compare the average annual return between marginal and established farming areas and determine which economic and production factors have influenced this change. The impact of this analysis will also be discussed in relation to rural land appraisal.

Trends in online journalism : a case study approach based on euaustralia online

This paper takes stock of current changes affecting journalism, and as a case study brings up to date the record of progress made with an online publishing enterprise, EUAustralia Online, first reported on in 2007. It perceives the development of news publishing on line as being in two sectors: media corporations moving to occupy the online publishing field, through complex business stratagems and product-making, and small publications enjoying low production costs and the ability to strike up relationships with numerous users, even on a mass scale. Recent developments in both major publishing and niche publishing are appraised in a literature review, considering both broad-scale industry trends; and pressure from fresh advances in information and communication technology to produce ever-more sophisticated media artefacts, like multi-platform news coverage. The paper also recounts the pattern of work on EUAustralia Online, showing how such publications, ubiquitous ‘blogs’ or newsletters, may be placed in a prospective online order, where large and small operations might co-exist.

Social networking : investigating the features of Facebook application

Research on social networking sites like Facebook is emerging but sparse. The exploratory study investigates the value users derive from self-described ‘cool’ Facebook applications, and explores the features that either encourage or discourage users to recommend application to their friends. Thus the concepts of value and cool are explored in a social networking setting. Our qualitative data shows that consumers derive a combination of functional value along with either social or emotional value from the applications. Female Facebook users indicated self-expression as important, while mates then to use Facebook application to socially compete. Three broad categories emerged for application features; symmetrical features can both encourage or discourage recommendation, asymmetrical features one encourage or discourage but not both, and polar features where different levels of the same feature encourage or discourage. Recommending or not recommending an application tends to be the result of a combination of features rather than one feature in isolation.

The studio sans frontières : the open-studio as an answer to the challenges of teaching contemporary art

Since at least the 1960s, art has assumed a breadth of form and medium as diverse as social reality itself. Where once it was marginal and transgressive for artists to work across a spectrum of media, today it is common practice. In this ‘post-medium’ age, fidelity to a specific branch of media is a matter of preference, rather than a code of practice policed by gallerists, curators and critics. Despite the openness of contemporary art practice, the teaching of art at most universities remains steadfastly discipline-based. Discipline-based art teaching, while offering the promise of focussed ‘mastery’ of a particular set of technical skills and theoretical concerns, does so at the expense of a deeper and more complex understanding of the possibilities of creative experimentation in the artist’s studio. By maintaining an hermetic approach to medium, it does not prepare students sufficiently for the reality of art making in the twenty-first century. In fact, by pretending that there is a select range of techniques fundamental to the artist’s trade, discipline-based teaching can often appear to be more engaged with the notion of skills preservation than purposeful art training. If art schools are to survive and prosper in an increasingly vocationally-oriented university environment, they need to fully synthesise the professional reality of contemporary art practice into their approach to teaching and learning. This paper discusses the way in which the ‘open’ studio approach to visual art study at QUT endeavours to incorporate the diversity and complexity of contemporary art while preserving the sense of collective purpose that discipline-based teaching fosters. By allowing students to independently develop their own art practices while also applying collaborative models of learning and assessment, the QUT studio program aims to equip students with a strong sense of self-reliance, a broad awareness and appreciation of contemporary art, and a deep understanding of studio-based experimentation unfettered by the boundaries of traditional media: all skills fundamental to the practice of contemporary art.

Mainstreaming sustainability into pre-service teacher edcuation in Australia

There is a growing interest in and support for education for sustainability in Australian schools. Australian Government schemes such as the Australian Sustainable Schools Initiative (AuSSI), along with strategies such as Educating for a Sustainable Future: A National Environmental Education Statement for Australian Schools(NEES(Australian Government and Curriculum Corporation (2005) and Living Sustainably: The Australian Government’s National Action Plan for Education for Sustainability (Australian Government 2009), recognise the need and offer support for education for sustainability in Australian schools. The number of schools that have engaged with AuSSI indicates that this interest also exists within Australian schools. Despite this, recent research indicates that pre-service teacher education institutions and programs are not doing all they can to prepare teachers for teaching education for sustainability or for working within sustainable schools. The education of school teachers plays a vital role in achieving changes in teaching and learning in schools. Indeed, the professional development of teachers in education for sustainability has been identified as ‘the priority of priorities’. Much has been written about the need to ‘reorient teacher education towards sustainability’. Teacher education is seen as a key strategy that is yet to be effectively utilised to embed education for sustainability in schools. Mainstreaming sustainability in Australian schools will not be achieved without the preparation of teachers for this task. The Mainstreaming Sustainability model piloted in this study seeks to engage a range of stakeholder organisations and key agents of change within a system to all work simultaneously to bring about a change, such as the mainstreaming of sustainability. The model is premised on the understanding that sustainability will be mainstreamed within teacher education if there is engagement with key agents of change across the wider teacher education system and if the key agents of change are ‘deeply’ involved in making the change. The model thus seeks to marry broad engagement across a system with the active participation of stakeholders within that system. Such a systemic approach is a way of bringing together diverse viewpoints to make sense of an issue and harness that shared interpretation to define boundaries, roles and relationships leading to a better defined problem that can be acted upon more effectively. Like action research, the systemic approach is also concerned with modelling change and seeking plausible solutions through collaboration between stakeholders. This is important in ensuring that outcomes are useful to the researchers/stakeholders and the system being researched as it creates partnerships and commitments to the outcomes by stakeholder participants. The study reported on here examines whether the ‘Mainstreaming Sustainability’ model might be effective as a means to mainstream sustainability in pre-service teacher education. This model, developed in an earlier study, was piloted in the Queensland teacher education system in order to examine its effectiveness in creating organisational and systemic change. The pilot project in Queensland achieved a number of outcomes. The project: • provided useful insights into the effectiveness of the Mainstreaming Sustainability model in bringing about change while also building research capacity within the system • developed capacities within the teacher education community: o developing competencies in education for sustainability o establishing more effective interactions between decision-makers and other stakeholders o establishing a community of inquiry • changed teaching and learning approaches used in participating teacher education institutions through: o curriculum and resource development o the adoption of education for sustainability teaching and learning processes o the development of institutional policies • improved networks within the teacher education system through: o identifying key agents of change within the system o developing new, and building on existing, partnerships between schools, teacher education institutions and government agencies • engaged relevant stakeholders such as government agencies and non-government organisations to understand and support the change Our findings indicate that the Mainstreaming Sustainability model is able to facilitate organisational and systemic change – over time – if: • the individuals involved have the conceptual and personal capacities needed to facilitate change, that is, to be a key agent of change • stakeholders are engaged as participants in the process of change, not simply as ‘interested parties’ • there is a good understanding of systemic change and the opportunities for leveraging change within systems. In particular, in seeking to mainstream sustainability in pre-service teacher education in Queensland it has become clear that one needs to build capacity for change within participants such as knowledge of education for sustainability, conceptual skills in systemic thinking, action research and organisational change, and leadership skills. It is also of vital importance that key agents of change – those individuals who are ‘hubs’ within a system and can leverage for change across a wide range of the system – are identified and engaged with as early as possible. Key agents of change can only be correctly identified, however, if the project leaders and known participants have clearly identified the boundary to their system as this enables the system, sub-system and environment of the system to be understood. Through mapping the system a range of key organisations and stakeholders will be identified, including government and nongovernment organisations, teacher education students, teacher education academics, and so on. On this basis, key agents of change within the system and sub-system can be identified and invited to assist in working for change. A final insight is that it is important to have time – and if necessary the funding to ‘buy time’ – in seeking to bring about system-wide change. Seeking to bring about system-wide change is an ambitious project, one that requires a great deal of effort and time. These insights provide some considerations for those seeking to utilise the Mainstreaming Sustainability model to bring about change within and across a pre-service teacher education system.

Towards a model of the institutional logics of climate change

The proliferation of innovative schemes to address climate change at international, national and local levels signals a fundamental shift in the priority and role of the natural environment to society, organizations and individuals. This shift in shared priorities invites academics and practitioners to consider the role of institutions in shaping and constraining responses to climate change at multiple levels of organisations and society. Institutional theory provides an approach to conceptualising and addressing climate change challenges by focusing on the central logics that guide society, organizations and individuals and their material and symbolic relationship to the environment. For example, framing a response to climate change in the form of an emission trading scheme evidences a practice informed by a capitalist market logic (Friedland and Alford 1991). However, not all responses need necessarily align with a market logic. Indeed, Thornton (2004) identifies six broad societal sectors each with its own logic (markets, corporations, professions, states, families, religions). Hence, understanding the logics that underpin successful –and unsuccessful– climate change initiatives contributes to revealing how institutions shape and constrain practices, and provides valuable insights for policy makers and organizations. This paper develops models and propositions to consider the construction of, and challenges to, climate change initiatives based on institutional logics (Thornton and Ocasio 2008). We propose that the challenge of understanding and explaining how climate change initiatives are successfully adopted be examined in terms of their institutional logics, and how these logics evolve over time. To achieve this, a multi-level framework of analysis that encompasses society, organizations and individuals is necessary (Friedland and Alford 1991). However, to date most extant studies of institutional logics have tended to emphasize one level over the others (Thornton and Ocasio 2008: 104). In addition, existing studies related to climate change initiatives have largely been descriptive (e.g. Braun 2008) or prescriptive (e.g. Boiral 2006) in terms of the suitability of particular practices. This paper contributes to the literature on logics by examining multiple levels: the proliferation of the climate change agenda provides a site in which to study how institutional logics are played out across multiple, yet embedded levels within society through institutional forums in which change takes place. Secondly, the paper specifically examines how institutional logics provide society with organising principles –material practices and symbolic constructions– which enable and constrain their actions and help define their motives and identity. Based on this model, we develop a series of propositions of the conditions required for the successful introduction of climate change initiatives. The paper proceeds as follows. We present a review of literature related to institutional logics and develop a generic model of the process of the operation of institutional logics. We then consider how this is applied to key initiatives related to climate change. Finally, we develop a series of propositions which might guide insights into the successful implementation of climate change practices.

Does chemometrics enhance the performance of electroanalysis?

This review explores the question whether chemometrics methods enhance the performance of electroanalytical methods. Electroanalysis has long benefited from the well-established techniques such as potentiometric titrations, polarography and voltammetry, and the more novel ones such as electronic tongues and noses, which have enlarged the scope of applications. The electroanalytical methods have been improved with the application of chemometrics for simultaneous quantitative prediction of analytes or qualitative resolution of complex overlapping responses. Typical methods include partial least squares (PLS), artificial neural networks (ANNs), and multiple curve resolution methods (MCR-ALS, N-PLS and PARAFAC). This review aims to provide the practising analyst with a broad guide to electroanalytical applications supported by chemometrics. In this context, after a general consideration of the use of a number of electroanalytical techniques with the aid of chemometrics methods, several overviews follow with each one focusing on an important field of application such as food, pharmaceuticals, pesticides and the environment. The growth of chemometrics in conjunction with electronic tongue and nose sensors is highlighted, and this is followed by an overview of the use of chemometrics for the resolution of complicated profiles for qualitative identification of analytes, especially with the use of the MCR-ALS methodology. Finally, the performance of electroanalytical methods is compared with that of some spectrophotometric procedures on the basis of figures-of-merit. This showed that electroanalytical methods can perform as well as the spectrophotometric ones. PLS-1 appears to be the method of practical choice if the %relative prediction error of not, vert, similar±10% is acceptable.

Measuring episodic memory: A novel approach with an indefinite number of alternative forms

Both clinical practice and clinical research settings can require successive administrations of a memory test, particularly when following the trajectory of suspected memory decline in older adults. However, relatively few verbal episodic memory tests have alternative forms. We set out to create a broad based memory test to allow for the use of an essentially unlimited number of alternative forms. Four tasks for inclusion in such a test were developed. These tasks varied the requirement for recall as opposed to recognition, the need to form an association between unrelated words, and the need to discriminate the most recent list from earlier lists, all of which proved useful. A total of 115 participants completed the battery of tests and were used to show that the test could differentiate between older and younger adults; a sub-sample of 73 participants completed alternative forms of the tests to determine test-retest reliability and the amount of learning to learn.

Magnitude and variability of loading on the osseointegrated implant of transfemoral amputees during walking

This study directly measured the load acting on the abutment of the osseointegrated implant system of transfemoral amputees during level walking, and studied the variability of the load within and among amputees. Twelve active transfemoral amputees (age: 54±12 years, mass:84.3±16.3 kg, height: 17.8±0.10 m) fitted with an osseointegrated implant for over 1 year participated in the study. The load applied on the abutment was measured during unimpeded, level walking in a straight line using a commercial six-channel transducer mounted between the abutment and the prosthetic knee. The pattern and the magnitude of the three-dimensional forces and moments were revealed. Results showed a low step-to-step variability of each subject, but a high subject-to-subject variability in local extrema of body-weight normalized forces and moments and impulse data. The high subject-to-subject variability suggests that the mechanical design of the implant system should be customized for each individual, or that a fit-all design should take into consideration the highest values of load within a broad range of amputees. It also suggests specific loading regime in rehabilitation training are necessary for a given subject. Thus the loading magnitude and variability demonstrated should be useful in designing an osseointegrated implant system better able to resist mechanical failure and in refining the rehabilitation protocol.