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    Predictors of future stroke in adults 60-64 years living in the community

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    AIM: To investigate predictors of incident stroke in a large epidemiological sample of cognitively healthy individuals in their early 60’s. METHODS: Cardiovascular (systolic and diastolic blood pressure, hypertension status and medication, body mass index, lung forced vital capacity), lifestyle (alcohol intake, smoking, physical activity), mental health (anxiety and depression status, medication and symptomatology), cognition (executive function, processing speed, working memory, sensorimotor skills), and personality measures (behavioural inhibition and activation, positive and negative affect, neuroticism, psychoticism, extraversion) were investigated as predictors of incident stroke in 1774 participants from the Personality and Total Health Through Life Project over an 8-year follow-up. Logistic regression analyses controlled for age, gender, and education were conducted in the whole cohort as well as in case-control sub-analyses including precisely matched controls to identify factors associated with stroke incidence. RESULTS: The cohort selected had a mean age of 62.5 years (SD = 1.5) and was 48.6% female with an average of 14.1 years of education (SD = 2.6). When 28 individuals with incident stroke were compared to 1746 cognitively healthy individuals in multivariate logistic regression analyses the only significant predictors of stroke across the five domains considered (cardiovascular, lifestyle, mental health, cognition, personality) and after controlling for gender, age, and education were systolic blood pressure (per unit above 140 mmHg: OR = 1.04, 95%CI: 1.01-1.07, P = 0.002), smoking (trend OR = 2.28, 95%CI: 0.99-5.24, P = 0.052), and sensorimotor skills (purdue pegboard: OR = 0.80, 95%CI: 0.62-0.96, P = 0.037). Similarly, in matched-control analyses significant group differences were found for systolic blood pressure (P = 0.001), smoking (P = 0.036), and sensorimotor skills (P = 0.028). CONCLUSION: Identified predictors of incident stroke in community-living individuals included high systolic blood pressure and smoking - but also, sensorimotor performance, a measure which has not yet been reported in the literature.Supported by The Dementia Collaborative Research Centre; the Centre for Excellence in Ageing Research; National Health and Medical Research Council of Australia, Nos. 973302, 179805, 157125; Australian Research Council, No. 130101705; Cherbuin N is funded by Australian Research Council Future Fellowship, No. 120100227; Mortby M by an Alzheimer Australia Foundation Fellowship; Anstey KJ by National Health and Medical Research Council Fellowship, No.1002560; Carey L by Australian Research Council Future Fellowship, No. 0992299; the James S. McDonnell Foundation 21st Century Science Initiative in Cognitive Rehabilitation -Collaborative Award, No. 220020413; and the Victorian Government’s Operational Infrastructure Support Program

    High incidence of hospitalisation due to infectious gastroenteritis in older people associated with poor self-rated health

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    Objectives To estimate the incidence and risk factors for gastroenteritis-related hospitalisations in older adults. Design Longitudinal cohort study. Participants The 45 and Up Study is a large-scale Australian prospective study of adults aged ≥45 years (mean 62.7 years) at recruitment in 2006–2009. Self-reported demographic, health and dietary information at recruitment from 265 440 participants were linked to infectious gastroenteritis hospitalisation data. Outcome measures We estimated the incidence of hospitalisation for infectious gastroenteritis, and calculated HRs using Cox regression, adjusting for sociodemographic, health and behavioural variables, with age as the underlying time variable. Results There were 6077 incident infectious gastroenteritis admissions over 1 111 000 person-years. Incidence increased exponentially with increasing age; from 2.4 per 1000 (95% CI 2.2 to 2.5) in individuals aged 45–54 years to 9.5 per 1000 (95% CI 9.2 to 9.8) in those aged 65+ years. After adjustment, hospitalisation due to infectious gastroenteritis was significantly more common in those reporting use of proton pump inhibitors (HR 1.6, 95% CI 1.5 to 1.7), and those with poorer self-rated health (HR 4.2, 95% CI 3.6 to 4.9). Conclusions Infectious gastroenteritis results in hospitalisation of approximately 1% of people ≥65 years old each year. Early recognition and supportive treatment of diarrhoea in older patients with poorer self-rated health may prevent subsequent hospitalisation

    International journal of project management special issue on “project benefit management”

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    The project management literature and international standards have been preoccupied with delivering outputs (artifacts such as a bridge). Accordingly, project management methodologies and tools are focused on enhancing the efficiency of output delivery — on time, within budget and at specifications. While this approach is well-founded, a sole focus on efficient delivery of outputs does not support project effectiveness. Recently, a wider view of projects has emerged, which recognizes their role in the creation of strategic value (Shenhar and Dvir, 2007 and Zwikael and Smyrk, 2015). Such a view accepts that organizations invest in projects with the specific objective of realizing identified target benefits

    Improved representation of plant functional types and physiology in the Joint UK Land Environment Simulator (JULES v4.2) using plant trait information

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    Dynamic global vegetation models are used to predict the response of vegetation to climate change. They are essential for planning ecosystem management, understanding carbon cycle–climate feedbacks, and evaluating the potential impacts of climate change on global ecosystems. JULES (the Joint UK Land Environment Simulator) represents terrestrial processes in the UK Hadley Centre family of models and in the first generation UK Earth System Model. Previously, JULES represented five plant functional types (PFTs): broadleaf trees, needle-leaf trees, C3 and C4 grasses, and shrubs. This study addresses three developments in JULES. First, trees and shrubs were split into deciduous and evergreen PFTs to better represent the range of leaf life spans and metabolic capacities that exists in nature. Second, we distinguished between temperate and tropical broadleaf evergreen trees. These first two changes result in a new set of nine PFTs: tropical and temperate broadleaf evergreen trees, broadleaf deciduous trees, needle-leaf evergreen and deciduous trees, C3 and C4 grasses, and evergreen and deciduous shrubs. Third, using data from the TRY database, we updated the relationship between leaf nitrogen and the maximum rate of carboxylation of Rubisco (Vcmax/, and updated the leaf turnover and growth rates to include a trade-off between leaf life span and leaf mass per unit area. Overall, the simulation of gross and net primary productivity (GPP and NPP, respectively) is improved with the nine PFTs when compared to FLUXNET sites, a global GPP data set based on FLUXNET, and MODIS NPP. Compared to the standard five PFTs, the new nine PFTs simulate a higher GPP and NPP, with the exception of C3 grasses in cold environments and C4 grasses that were previously over-productive. On a biome scale, GPP is improved for all eight biomes evaluated and NPP is improved for most biomes – the exceptions being the tropical forests, savannahs, and extratropical mixed forests where simulated NPP is too high. With the new PFTs, the global present-day GPP and NPP are 128 and 62 PgC year1, respectively. We conclude that the inclusion of trait-based data and the evergreen/deciduous distinction has substantially improved productivity fluxes in JULES, in particular the representation of GPP. These developments increase the realism of JULES, enabling higher confidence in simulations of vegetation dynamics and carbon storage.We gratefully acknowledge all funding bodies. AH was funded by the NERC Joint Weather and Climate Research Programme and NERC grant NE/K016016/1. The study has been supported by the TRY initiative on plant traits ( O. K. Atkin acknowledges the support of the Australian Research Council (CE140100008). Met Office authors were supported by the Joint DECC/Defra Met Office Hadley Centre Climate Programme (GA01101). V. Onipchenko was supported by RSF (RNF) (project 14-50-00029). J. Peñuelas acknowledges support from the European Research Council Synergy grant ERCSyG- 2013-610028, IMBALANCE-P, and ÜN from the advanced grant ERC-AdG-322603, SIP-VOLC

    Inspiratory muscle training to enhance recovery from mechanical ventilation: a randomised trial

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    BACKGROUND In patients who have been mechanically ventilated, inspiratory muscles remain weak and fatigable following ventilatory weaning, which may contribute to dyspnoea and limited functional recovery. Inspiratory muscle training may improve inspiratory muscle strength and endurance following weaning, potentially improving dyspnoea and quality of life in this patient group. METHODS We conducted a randomised trial with assessor-blinding and intention-to-treat analysis. Following 48 hours of successful weaning, 70 participants (mechanically ventilated ≥7 days) were randomised to receive inspiratory muscle training once daily 5 days/week for 2 weeks in addition to usual care, or usual care (control). Primary endpoints were inspiratory muscle strength and fatigue resistance index (FRI) 2 weeks following enrolment. Secondary endpoints included dyspnoea, physical function and quality of life, post-intensive care length of stay and in-hospital mortality. RESULTS 34 participants were randomly allocated to the training group and 36 to control. The training group demonstrated greater improvements in inspiratory strength (training: 17%, control: 6%, mean difference: 11%, p=0.02). There were no statistically significant differences in FRI (0.03 vs 0.02, p=0.81), physical function (0.25 vs 0.25, p=0.97) or dyspnoea (-0.5 vs 0.2, p=0.22). Improvement in quality of life was greater in the training group (14% vs 2%, mean difference 12%, p=0.03). In-hospital mortality was higher in the training group (4 vs 0, 12% vs 0%, p=0.051). CONCLUSIONS Inspiratory muscle training following successful weaning increases inspiratory muscle strength and quality of life, but we cannot confidently rule out an associated increased risk of in-hospital mortality. TRIAL REGISTRATION NUMBER ACTRN12610001089022, results.We gratefully acknowledge the Canberra Hospital Private Practice Fund (2010) and the Canberra Hospital Auxiliary Research Fund for supporting this study. We also gratefully acknowledge the support of the University of Canberra Health Research Institute

    Quasi-phase matching via femtosecond laser-induced domain inversion in lithium niobate waveguides

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    We demonstrate an all-optical fabrication method of quasi-phase matching structures in lithium niobate (LiNbO₃) waveguides using a tightly focused femtosecond near-infrared laser beam (wavelength of 800 nm). In contrast to other all-optical schemes that utilize a periodic lowering of the nonlinear coefficient ⁽²⁾ by material modification, here the illumination of femtosecond pulses directly reverses the sign of ⁽²⁾ through the process of ferroelectric domain inversion. The resulting quasi-phase matching structures, therefore, lead to more efficient nonlinear interactions. As an experimental demonstration, we fabricate a structure with the period of 2.74 μm to frequency double 815 nm light. A maximum conversion efficiency of 17.45% is obtained for a 10 mm long waveguide.Australian Research Council (ARC); Qatar National Research Fund (NPRP 8-246-1-060)

    Characterisation of minimalist co-assembled fluorenylmethyloxycarbonyl self-assembling peptide systems for presentation of multiple bioactive peptides

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    UNLABELLED The nanofibrillar structures that underpin self-assembling peptide (SAP) hydrogels offer great potential for the development of finely tuned cellular microenvironments suitable for tissue engineering. However, biofunctionalisation without disruption of the assembly remains a key issue. SAPS present the peptide sequence within their structure, and studies to date have typically focused on including a single biological motif, resulting in chemically and biologically homogenous scaffolds. This limits the utility of these systems, as they cannot effectively mimic the complexity of the multicomponent extracellular matrix (ECM). In this work, we demonstrate the first successful co-assembly of two biologically active SAPs to form a coassembled scaffold of distinct two-component nanofibrils, and demonstrate that this approach is more bioactive than either of the individual systems alone. Here, we use two bioinspired SAPs from two key ECM proteins: Fmoc-FRGDF containing the RGD sequence from fibronectin and Fmoc-DIKVAV containing the IKVAV sequence from laminin. Our results demonstrate that these SAPs are able to co-assemble to form stable hybrid nanofibres containing dual epitopes. Comparison of the co-assembled SAP system to the individual SAP hydrogels and to a mixed system (composed of the two hydrogels mixed together post-assembly) demonstrates its superior stable, transparent, shear-thinning hydrogels at biological pH, ideal characteristics for tissue engineering applications. Importantly, we show that only the coassembled hydrogel is able to induce in vitro multinucleate myotube formation with C2C12 cells. This work illustrates the importance of tissue engineering scaffold functionalisation and the need to develop increasingly advanced multicomponent systems for effective ECM mimicry. STATEMENT OF SIGNIFICANCE Successful control of stem cell fate in tissue engineering applications requires the use of sophisticated scaffolds that deliver biological signals to guide growth and differentiation. The complexity of such processes necessitates the presentation of multiple signals in order to effectively mimic the native extracellular matrix (ECM). Here, we establish the use of two biofunctional, minimalist self-assembling peptides (SAPs) to construct the first co-assembled SAP scaffold. Our work characterises this construct, demonstrating that the physical, chemical, and biological properties of the peptides are maintained during the co-assembly process. Importantly, the coassembled system demonstrates superior biological performance relative to the individual SAPs, highlighting the importance of complex ECM mimicry. This work has important implications for future tissue engineering studies.Access to the facilities of the Centre for Advanced Microscopy (CAM) with funding through the Australian Microscopy and Microanalysis Research Facility (AMMRF) is gratefully acknowledged. SAXS experiments undertaken on the SAXS/WAXS beamline at the Australian Synchrotron, Victoria, Australia are also gratefully acknowledged. We would also like to thank F. Maclean and A. Panneerselvan for thorough proof reading of the manuscript. This research was supported by funding from the Australian Research Council (ARC, DP130103131). ALR was supported by an Australian Postgraduate Award; RJW was funded via an Alfred Deakin Research Fellowship; DRN was supported by a NHMRC Career Development Fellowship (APP1050684)

    GMP Synthase Is Required for Virulence Factor Production and Infection by Cryptococcus neoformans

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    Over the last four decades the HIV pandemic and advances in medical treatments that also cause immunosuppression have produced an ever-growing cohort of individuals susceptible to opportunistic pathogens. Of these, AIDS patients are particularly vulnerable to infection by the encapsulated yeast Cryptococcus neoformans Most commonly found in the environment in purine-rich bird guano, C. neoformans experiences a drastic change in nutrient availability during host infection, ultimately disseminating to colonize the purine-poor central nervous system. Investigating the consequences of this challenge, we have characterized C. neoformans GMP synthase, the second enzyme in the guanylate branch of de novo purine biosynthesis. We show that in the absence of GMP synthase, C. neoformans becomes a guanine auxotroph, the production of key virulence factors is compromised, and the ability to infect nematodes and mice is abolished. Activity assays performed using recombinant protein unveiled differences in substrate binding between the C. neoformans and human enzymes, with structural insights into these kinetic differences acquired via homology modeling. Collectively, these data highlight the potential of GMP synthase to be exploited in the development of new therapeutic agents for the treatment of disseminated, life-threatening fungal infections.This work was supported by National Health and Medical Research Council Grant APP1049716 (to J. A. F. and M. S. B.), a Queensland Medical Research Scholarship (to J. C.), National Health and Medical Research Council Principle Research Fellowships 1003325 and 1110971 (to B. K.), and National Health and Medical Research Council Principle Research Fellowship GNT1059354 (to M. A. C.)

    Open Access to Journal Content as a Case Study in Unlocking IP

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    Big words, small phrases: Mismatches between pause units and the polysynthetic word in Dalabon

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    This article uses instrumental data from natural speech to examine the phenomenon of pause placement within the verbal word in Dalabon, a polysynthetic Australian language of Arnhem Land. Though the phenomenon is incipient and in two sample texts occurs in only around 4% of verbs, there are clear possibilities for interrupting the grammatical word by pause after the pronominal prefix and some associated material at the left edge, though these within-word pauses are significantly shorter, on average, than those between words. Within-word pause placement is not random, but is restricted to certain affix boundaries; it requires that the paused-after material be at least dimoraic, and that the remaining material in the verbal word be at least disyllabic. Bininj Gun-wok, another polysynthetic language closely related to Dalabon, does not allow pauses to interrupt the verbal word, and the Dalabon development appears to be tied up with certain morphological innovations that have increased the proportion of closed syllables in the pronominal prefix zone of the verb. Though only incipient and not yet phonologized, pause placement in Dalabon verbs suggests a phonology-driven route by which polysynthetic languages may ultimately become less morphologically complex by fracturing into smaller units


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