Novel TBK1 truncating mutation in a familial amyotrophic lateral sclerosis patient of Chinese origin

Missense and frameshift mutations in TRAF family member-associated NF-kappa-B activator (TANK)-binding kinase 1 (TBK1) have been reported in European sporadic and familial amyotrophic lateral sclerosis (ALS) cohorts. To assess the role of TBK1 in ALS patient cohorts of wider ancestry, we have analyzed whole-exome sequence data from an Australian cohort of familial ALS (FALS) patients and controls. We identified a novel TBK1 deletion (c.1197delC) in a FALS patient of Chinese origin. This frameshift mutation (p.L399fs) likely results in a truncated protein that lacks functional domains required for adapter protein binding, as well as protein activation and structural integrity. No novel or reported TBK1 mutations were identified in FALS patients of European ancestry. This is the first report of a TBK1 mutation in an ALS patient of Asian origin and indicates that sequence variations in TBK1 are a rare cause of FALS in Australia. © 2015 Elsevier Inc.

When and how to treat pulmonary non-tuberculous mycobacterial diseases

Nontuberculous mycobacteria are ubiquitous environmental organisms that have been recognised as a cause of pulmonary infection for over 50 years. Traditionally patients have had underlying risk factors for development of disease; however the proportion of apparently immunocompetent patients involved appears to be rising. Not all patients culture-positive for mycobacteria will have progressive disease, making the diagnosis difficult, though criteria to aid in this process are available. The two main forms of disease are cavitary disease (usually involving the upper lobes) and fibronodular bronchiectasis (predominantly middle and lingular lobes). For patients with disease, combination antibiotic therapy for 12-24 months is generally required for successful treatment, and this may be accompanied by drug intolerances and side effects. Published success rates range from 30-82%. As the progression of disease is variable, for some patients, attention to pulmonary hygiene and underlying diseases without immediate antimycobacterial therapy may be more appropriate. Surgery can be a useful adjunct, though is associated with risks. Randomised controlled trials in well described patients would provide stronger evidence-based data to guide therapy of NTM lung diseases, and thus are much needed.

How environmental and organizational complexity affects opportunity recognition and exploitation in development projects

Principal Topic: Project structures are often created by entrepreneurs and large corporate organizations to develop new products. Since new product development projects (NPDP) are more often situated within a larger organization, intrapreneurship or corporate entrepreneurship plays an important role in bringing these projects to fruition. Since NPDP often involves the development of a new product using immature technology, we describe development of an immature technology. The Joint Strike Fighter (JSF) F-35 aircraft is being developed by the U.S. Department of Defense and eight allied nations. In 2001 Lockheed Martin won a $19 billion contract to develop an affordable, stealthy and supersonic all-weather strike fighter designed to replace a wide range of aging fighter aircraft. In this research we define a complex project as one that demonstrates a number of sources of uncertainty to a degree, or level of severity, that makes it extremely difficult to predict project outcomes, to control or manage project (Remington & Zolin, Forthcoming). Project complexity has been conceptualized by Remington and Pollock (2007) in terms of four major sources of complexity; temporal, directional, structural and technological complexity (See Figure 1). Temporal complexity exists when projects experience significant environmental change outside the direct influence or control of the project. The Global Economic Crisis of 2008 - 2009 is a good example of the type of environmental change that can make a project complex as, for example in the JSF project, where project managers attempt to respond to changes in interest rates, international currency exchange rates and commodity prices etc. Directional complexity exists in a project where stakeholders' goals are unclear or undefined, where progress is hindered by unknown political agendas, or where stakeholders disagree or misunderstand project goals. In the JSF project all the services and all non countries have to agree to the specifications of the three variants of the aircraft; Conventional Take Off and Landing (CTOL), Short Take Off/Vertical Landing (STOVL) and the Carrier Variant (CV). Because the Navy requires a plane that can take off and land on an aircraft carrier, that required a special variant of the aircraft design, adding complexity to the project. Technical complexity occurs in a project using technology that is immature or where design characteristics are unknown or untried. Developing a plane that can take off on a very short runway and land vertically created may highly interdependent technological challenges to correctly locate, direct and balance the lift fans, modulate the airflow and provide equivalent amount of thrust from the downward vectored rear exhaust to lift the aircraft and at the same time control engine temperatures. These technological challenges make costing and scheduling equally challenging. Structural complexity in a project comes from the sheer numbers of elements such as the number of people, teams or organizations involved, ambiguity regarding the elements, and the massive degree of interconnectedness between them. While Lockheed Martin is the prime contractor, they are assisted in major aspects of the JSF development by Northrop Grumman, BAE Systems, Pratt & Whitney and GE/Rolls-Royce Fighter Engineer Team and innumerable subcontractors. In addition to identifying opportunities to achieve project goals, complex projects also need to identify and exploit opportunities to increase agility in response to changing stakeholder demands or to reduce project risks. Complexity Leadership Theory contends that in complex environments adaptive and enabling leadership are needed (Uhl-Bien, Marion and McKelvey, 2007). Adaptive leadership facilitates creativity, learning and adaptability, while enabling leadership handles the conflicts that inevitably arise between adaptive leadership and traditional administrative leadership (Uhl-Bien and Marion, 2007). Hence, adaptive leadership involves the recognition and opportunities to adapt, while and enabling leadership involves the exploitation of these opportunities. Our research questions revolve around the type or source of complexity and its relationship to opportunity recognition and exploitation. For example, is it only external environmental complexity that creates the need for the entrepreneurial behaviours, such as opportunity recognition and opportunity exploitation? Do the internal dimensions of project complexity, such as technological and structural complexity, also create the need for opportunity recognition and opportunity exploitation? The Kropp, Zolin and Lindsay model (2009) describes a relationship between entrepreneurial orientation (EO), opportunity recognition (OR), and opportunity exploitation (OX) in complex projects, with environmental and organizational contextual variables as moderators. We extend their model by defining the affects of external complexity and internal complexity on OR and OX. ---------- Methodology/Key Propositions: When the environment complex EO is more likely to result in OR because project members will be actively looking for solutions to problems created by environmental change. But in projects that are technologically or structurally complex project leaders and members may try to make the minimum changes possible to reduce the risk of creating new problems due to delays or schedule changes. In projects with environmental or technological complexity project leaders who encourage the innovativeness dimension of EO will increase OR in complex projects. But projects with technical or structural complexity innovativeness will not necessarily result in the recognition and exploitation of opportunities due to the over-riding importance of maintaining stability in the highly intricate and interconnected project structure. We propose that in projects with environmental complexity creating the need for change and innovation project leaders, who are willing to accept and manage risk, are more likely to identify opportunities to increase project effectiveness and efficiency. In contrast in projects with internal complexity a much higher willingness to accept risk will be necessary to trigger opportunity recognition. In structurally complex projects we predict it will be less likely to find a relationship between risk taking and OP. When the environment is complex, and a project has autonomy, they will be motivated to execute opportunities to improve the project's performance. In contrast, when the project has high internal complexity, they will be more cautious in execution. When a project experiences high competitive aggressiveness and their environment is complex, project leaders will be motivated to execute opportunities to improve the project's performance. In contrast, when the project has high internal complexity, they will be more cautious in execution. This paper reports the first stage of a three year study into the behaviours of managers, leaders and team members of complex projects. We conduct a qualitative study involving a Group Discussion with experienced project leaders. The objective is to determine how leaders of large and potentially complex projects perceive that external and internal complexity will influence the affects of EO on OR. ---------- Results and Implications: These results will help identify and distinguish the impact of external and internal complexity on entrepreneurial behaviours in NPDP. Project managers will be better able to quickly decide how and when to respond to changes in the environment and internal project events.

'My grandchild has a disability' : impact on grandparenting identity, roles and relationships

Being a grandparent is an important and valued role for many older adults, who often have strong views about the type of grandparent they will be and what they will teach their grandchild. When their grandchild has a disability, grandparents may have to significantly adjust their expectations and interactions. This research explores if and how having a grandchild with a disability influences grandparents’ sense of identity and enactment of the grandparent role. Using qualitative purposive sampling, semi-structured interviews were conducted with 22 grandparents of children with an intellectual and/or physical disability residing in Brisbane, Australia. A thematic analysis identified three key themes characterising grandparent’s views: formation of grandparenting identity, styles of grandparenting, and role enactment. The results highlight the critical role of grandparents when a child has a disability, illustrating that the grandparenting experience and role enactment may be universal with only the context and delivery varying.

Hospital to home outreach for malnourished elders (HHOME) : a feasibility pilot

Objectives: Malnutrition is common in older hospitalised patients, and barriers to adequate intake in hospital limit the effectiveness of hospital-based nutrition interventions. This pilot study was undertaken to determine whether nutrition-focussed care at discharge and in the early post-hospital period is feasible and acceptable to patients and carers, and improves nutritional status. Design: Prospective cohort study Setting: Internal medicine wards of a tertiary teaching hospital in Brisbane, Australia Participants: Patients aged 65 and older admitted for at least 3 days, identified as malnourished or at risk of malnutrition using Mini Nutritional Assessment (MNA). Interventions: An interdisciplinary discharge team (specialist discharge planning nurse and accredited practicing dietitian) provided nutrition-focussed education, advice, service coordination and follow-up (home visits and telephone) for 6 weeks following hospitalisation Measurements: Nutritional intake, weight, functional status and MNA were recorded 6 and 12 weeks after discharge. Service intensity and changes to care were noted, and hospital readmissions recorded. Service feedback from patients and carers was sought using a brief questionnaire. Results: 12 participants were enrolled during the 6 week pilot (mean age 82 years, 50% male). All received 1-2 home visits, and 3-8 telephone calls. Four participants had new community services arranged, 4 were commenced on oral nutritional supplements, and 7 were referred to community dietetics services for follow-up. Two participants had a decline in MNA score of more than 10% at 12 week follow-up, while the remainder improved by at least 10%. Individualised care including community service coordination was valued by participants. Conclusion: The proposed model of care for older adults was feasible, acceptable to patients and carers, and associated with improved nutritional status at 12 weeks for most participants. The pilot data will be useful for design of intervention trials.

Understanding neighbourhood liveability for older urban Australians

As with other major developed cities, the sub-tropical and fastest growing Australian capital city of Brisbane has adopted policies designed to increase residential densities and meet the liveability and sustainability goal of decreasing car dependence and greenhouse gas emissions. This goal hinges on a pedestrian friendly environment and walkable proximity to satisfy everyday needs. While older people are particularly attracted to sub-tropical urban environments, there has been little empirical evidence linking liveability satisfaction and perceived and actual use of older people’s urban neighbourhood. Using qualitative (diaries and in-depth interviews) and quantitative (Global Positioning Systems and Geographical Information Systems mapping) liveability research data this paper explores whether high density supports liveability and is sustainable for older people living in a sub-tropical urban environment. This paper links satisfaction and perceived use of the sub-tropical urban Brisbane environment with actual mapped characteristics and use. Linking the two methods (both quantitative and qualitative) is important in obtaining a greater understanding of human behaviour and the lived world of older urban Australians and in providing a wider picture of sub-tropical urban neighbourhoods for a significant population group within those neighbourhoods. What emerges from the research is an uneven standard of design, provision of amenities and maintenance of the public realm which negatively impacts on local neighbourhood participation by older urban Australians. By highlighting these issues this research furthers the understanding of design factors which make the sub-tropical urban neighbourhood more liveable and sustainable for older people and will inform actionable and implementable policies, programs and designs.

Students’ beliefs about willingness to access complementary and alternative therapies (CAT) training for future integration into psychology practice.

It is suggested that all psychologists gain basic training in the types of complementary and alternative therapies (CAT) their clients may be using. As psychology students are the next cohort of health professionals who will inform future initiatives in the field, it is important to first understand the factors which influence their decisions about CAT integration. Drawing on the Theory of Planned Behavior, we investigated the beliefs that differentiate between psychology students who are high or low on willingness to access training in CAT for future practice use. Psychology students (N = 106) completed a questionnaire assessing the likelihood of both positive and negative consequences of accessing training and utilizing CAT within a psychological practice, important others approval, and barriers preventing them from this integration behavior. Those students high compared to low on willingness more likely to endorse positive outcomes (e.g., offering a more holistic approach to therapy) of accessing CAT training for future practice use and to believe that important others (e.g., clients) would support this behavior. We identified important beliefs of student psychologists related to decisions about undertaking CAT training for future professional use and can inform educators and policy-makers about CAT training and integration in psychology practice.

How do older adults respond to Active Australia physical activity questions? Lessons from cognitive interviews

The aim of this study was to examine older adults’ understanding and interpretation of a validated questionnaire for physical activity surveillance, the Active Australia Survey (AAS). To address this aim, cognitive interviewing techniques were used during face-to-face semi-structured interviews with 44 adults aged 65-89 years. Qualitative data analysis revealed that participants were confused with questionnaire phrasing, misunderstood the scope of activities to include in answers, and misunderstood the time frame of activities to report. They also struggled to accurately estimate the frequency and duration of their activities. Our findings suggest that AAS questions may be interpreted differently by older adults than intended by survey developers. Findings also suggest that older adults use a range of methods for calculating PA frequency and duration. The issues revealed in this study may be useful for adapting AAS for use in older community-dwelling adults.

Social turkey

Social Turkey is a short digital dance video developed over a series of weekly meetings with a group of sprightly and defiant sixty-plus year olds resident in Limerick. Very early in the process artist Ciara Finnegan and choreographer Jenny Roche found each individual expressing a wonderful enthusiasm for dance, an eagerness to perform and a healthy refusal to conform to stereotypes of aging. Finnegan was keen that this project should support an exchange of ideas rather than employ a top-down directorial structure. While Roche devised the fundamentals of the dance and Finnegan manned the camera, each participant contributed thereafter - improvising on a step sequence and collaborating on patterns that ultimately determined much of the look of the result. The work seeks to amplify the represented interests of a wider community while celebrating the vivacity of the particular group and the sheer fun of the collaboration.

Species differences in acrylonitrile metabolism and toxicity between experimental animals and humans based on observations in human accidental poisonings

The high acute toxicity of acrylonitrile may be a result of its intrinsic biological reactivity or of its metabolite cyanide. Intravenous N-acetylcysteine has been recommended for treatment of accidental intoxications in acrylonitrile workers, but such recommendations vary internationally. Acrylonitrile is metabolized in humans and experimental animals via two competing pathways; the glutathione-dependent pathway is considered to represent an avenue of detoxication whilst the oxidative pathway leads to a genotoxic epoxide, cyanoethylene oxide, and to elimination of cyanide. Cases of acute acrylonitrile overexposure or intoxication have occurred within persons having industrial contact with acrylonitrile; the route of exposure was by inhalation and/or by skin contact. The combined observations lead to the conclusion of a much higher impact of the oxidative metabolism of acrylonitrile in humans than in rodents. This is confirmed by differences in the clinical picture of acute life-threatening intoxications in both species, as well as by differential efficacies of antidotes. A combination of N-acetylcysteine with sodium thiosulfate seems an appropriate measure for antidote therapy of acute acrylonitrile intoxications. Clinical observations also highlight the practical importance of human individual susceptibility differences. Furthermore, differential adduct monitoring, assessing protein adducts with different rates of decay, enables the development of more elaborated biological monitoring strategies for the surveillance of workers with potential acrylonitrile contact.

Nutritional challenges for the family caregiver and person with dementia dyad

ABSTRACT Background: The majority of people with dementia live at home until quite late in the disease trajectory, supported by family caregivers who typically take increasing responsibility for providing nutrition. Caregiving is highly stressful and thus both dyad partners are at risk of nutritional issues. Objective: This study evaluated the nutritional status of both dyad members and the associations between these. Design Descriptive, correlational Setting Community Participants 26 dyads of persons with dementia and caregivers Measurements: The nutritional status of each dyad member was evaluated at home using a comprehensive battery of measures including the Mini-Nutritional Assessment, Corrected Arm Muscle Area and a 3-day food diary. Stage of dementia and functional eating capacity was measured for the person with dementia. Caregivers completed a brief burden scale. Results: Of those with dementia (n = 26), a large proportion had nutritional issues (one was malnourished and another 16 were at risk). Six of the caregivers were at risk of malnutrition. In addition, fifteen of the people with dementia did not meet their recommended daily energy requirements. A moderate and significant positive correlation between functional eating skills and nutritional status (MNA score) among participants with dementia was found (r =.523, n = 26, p.006). Conclusion: These findings suggest that a dyadic perspective of nutritional status provides important insights into risk in this vulnerable group. Specifically, monitoring of the functional eating independence skills of the person with dementia is critical, along with assisting caregivers to be aware of their own eating patterns and intake.

Disorganising principles: Corporeal fragmentation and the possibilities for repair

Dancers investigate ever-expanding relationships to embodiment through the variety of unique choreographic signatures that are continually erupting in professional practice. They live fragmented lineages that are interrupted and redirected as they traverse between various projects led by different choreographers or the same choreographer pursuing different creative goals. As contemporary dance continues to reconceive ways of moving, the dominant lineages of dance training are less useful as reference points through which dancers can recalibrate bodily activity and thus rebalance. In this chapter, I examine the impulse towards fragmentation in contemporary dance and explore how moments of agency for dancers might arise and be seized within the complexities of this environment. These issues are discussed in relation to my encounter with a bodywork therapy of Japanese origin, Amatsu, which I studied throughout 2012, and through the teaching principles of Gill Clarke as illuminated through the Minding Motion project, which explored Clarke’s pedagogy for Tanzplan, Germany 2010 (Diehl and Lampert, 2011). Moments from performance and bodywork practice are offered as examples throughout the chapter.

Genome-wide interaction analysis reveals replicated epistatic effects on brain structure

The discovery of several genes that affect the risk for Alzheimer's disease ignited a worldwide search for single-nucleotide polymorphisms (SNPs), common genetic variants that affect the brain. Genome-wide search of all possible SNP-SNP interactions is challenging and rarely attempted because of the complexity of conducting approximately 1011 pairwise statistical tests. However, recent advances in machine learning, for example, iterative sure independence screening, make it possible to analyze data sets with vastly more predictors than observations. Using an implementation of the sure independence screening algorithm (called EPISIS), we performed a genome-wide interaction analysis testing all possible SNP-SNP interactions affecting regional brain volumes measured on magnetic resonance imaging and mapped using tensor-based morphometry. We identified a significant SNP-SNP interaction between rs1345203 and rs1213205 that explains 1.9% of the variance in temporal lobe volume. We mapped the whole brain, voxelwise effects of the interaction in the Alzheimer's Disease Neuroimaging Initiative data set and separately in an independent replication data set of healthy twins (Queensland Twin Imaging). Each additional loading in the interaction effect was associated with approximately 5% greater brain regional brain volume (a protective effect) in both Alzheimer's Disease Neuroimaging Initiative and Queensland Twin Imaging samples.

Tracking Alzheimer's disease

Population-based brain mapping provides great insight into the trajectory of aging and dementia, as well as brain changes that normally occur over the human life span.We describe three novel brain mapping techniques, cortical thickness mapping, tensor-based morphometry (TBM), and hippocampal surface modeling, which offer enormous power for measuring disease progression in drug trials, and shed light on the neuroscience of brain degeneration in Alzheimer's disease (AD) and mild cognitive impairment (MCI).We report the first time-lapse maps of cortical atrophy spreading dynamically in the living brain, based on averaging data from populations of subjects with Alzheimer's disease and normal subjects imaged longitudinally with MRI. These dynamic sequences show a rapidly advancing wave of cortical atrophy sweeping from limbic and temporal cortices into higher-order association and ultimately primary sensorimotor areas, in a pattern that correlates with cognitive decline. A complementary technique, TBM, reveals the 3D profile of atrophic rates, at each point in the brain. A third technique, hippocampal surface modeling, plots the profile of shape alterations across the hippocampal surface. The three techniques provide moderate to highly automated analyses of images, have been validated on hundreds of scans, and are sensitive to clinically relevant changes in individual patients and groups undergoing different drug treatments. We compare time-lapse maps of AD, MCI, and other dementias, correlate these changes with cognition, and relate them to similar time-lapse maps of childhood development, schizophrenia, and HIV-associated brain degeneration. Strengths and weaknesses of these different imaging measures for basic neuroscience and drug trials are discussed.