1,459 research outputs found

    A Small BVAR-DSGE Model for Forecasting the Australian Economy

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    This paper estimates a small structural model of the Australian economy, designed principally for forecasting the key macroeconomic variables of output growth, underlying inflation and the cash rate. In contrast to models with purely statistical foundations, which are often used for forecasting, the Bayesian Vector Autoregressive Dynamic Stochastic General Equilibrium (BVAR-DSGE) model uses the theoretical information of a DSGE model to offset in-sample over-fitting. We follow the method of Del Negro and Schorfheide (2004) and use a variant of the small open economy DSGE model of Lubik and Schorfheide (2007) to provide prior information for the VAR. The forecasting performance of the model is competitive with benchmark models such as a Minnesota VAR and an independently estimated DSGE model.BVAR-DSGE; forecasting

    Age-Related Changes in Proximal Humerus Bone Health in White Males

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    poster abstractThe proximal humerus is a common site for osteoporotic fracture during aging, accounting for up to 5% of fractures to the appendicular skeleton. While falls onto an outstretched hand are usually physically responsible for proximal humerus fractures, the ability of the underlying bone to resist applied loads must also play a role. Few studies have assessed proximal humerus bone health with aging. The aim of the current study was to explore age-related bone changes at the proximal humerus in men. A cross-sectional study design was used to assess peripheral quantitative computed tomography (pQCT)-derived bone properties of the proximal humerus in a cohort of 112 white males (age range = 30-85 yrs). A tomographic slice of the non-dominant upper extremity was acquired at 80% of humeral length proximal from its distal end—a location corresponding to the surgical neck of the humerus. Images were assessed for cortical (Ct.BMC) and trabecular (Tb.BMC) BMC, total (Tt.Ar), cortical (Ct.Ar) and medullary (Me.Ar) area, periosteal (Ps.Pm) and endosteal (Es.Pm) perimeter, cortical thickness (Ct.Th), and bone strength index for compression (BSIc). BSIc was calculated as the product of Tt.Ar and the square of total volumetric BMD. Data were plotted against age and linear regression lines assessed for their slope. Slopes were subsequently converted to percent change in the bone property per year. During aging, the proximal humerus expanded with Tt.Ar and Ps.Pm increasing at rates of 0.40%/yr and 0.19%/yr, respectively. However, Me.Ar (0.62%/yr) and Es.Pm (0.34%/yr) expanded at faster rates such that there was net loss of both Ct.BMC (-0.23%/yr) and Tb.BMC (-1.08%/yr). Also, the more rapid expansion of Me.Ar relative to Tt.Ar meant that Ct.Ar (-0.15%/yr) and Ct.Th (-0.34%/yr) both decreased with age. The net result of these mass and structural changes was progressive loss of bone strength with age, as indicated by a 0.44%/yr decline in BSIc. These data provide a picture of bone changes at the proximal humerus during aging. They suggest that between age 30 and 80 yrs, approximately 54% and 11% of Tb.BMC and Ct.BMC at the proximal humerus is lost, respectively. They also suggest that compressive strength of the proximal humerus declines by 22% between age 30 and 80 years. These declines in proximal humerus bone health have implications for fracture risk at this location during aging

    Exercise Completed When Young Provides Lifelong Benefit to Cortical Bone Structure and Estimated Strength

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    poster abstractExercise induces greatest bone gains during growth, yet reduced bone strength is an age-related phenomenon. This raises the question of whether exercise-induced bone changes when young persist into adulthood. The current studies used Major/Minor League Baseball (MLB/MiLB) players to explore whether exercise-induced gains in humeral bone structure and strength accrued when young persist lifelong. MLB/MiLB players are a unique model as the unilateral upper extremity loading associated with throwing enables the contralateral side to serve as an internal control site and former MLB/MiLB players were consistently exposed to extreme loading reducing secular variations in exercise levels between generations. Dominant-to-nondominant (D-to-ND) differences in humeral cross-sectional properties in MLB/MiLB players were normalized to matched controls to correct for side-to-side differences due to elevated habitual loading associated with arm dominance. Exercise when young induced significant skeletal benefits, with active MLB/MiLB players having nearly double the estimated ability to resist torsion (polar moment of inertia, IP) in the humerus of their dominant arm. The cortical bone mass and area benefits of exercise observed in active MLB/MiLB players were lost in former MLB players following 40-49 years of detraining as a result of elevated medullary expansion and endocortical trabecularization. However, 42% of the total bone area benefit persisted following 50+ years of detraining and contributed to the maintenance of 24% of the benefit on IP. In MLB players who continued to exercise during aging, medullary expansion and endocortical trabecularization were reduced and there was maintenance of the cortical bone mass and area benefits of exercise. These cumulative data indicate: 1) the extreme plasticity of the growing skeleton to exercise; 2) that exercise when young has lifelong benefits on cortical bone size and estimated strength, but not bone mass, and; 3) exercise continued during aging maintains the bone mass benefits of exercise

    Antigen-presenting genes and genomic copy number variations in the Tasmanian devil MHC

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    BACKGROUND The Tasmanian devil (Sarcophilus harrisii) is currently under threat of extinction due to an unusual fatal contagious cancer called Devil Facial Tumour Disease (DFTD). DFTD is caused by a clonal tumour cell line that is transmitted between unrelated individuals as an allograft without triggering immune rejection due to low levels of Major Histocompatibility Complex (MHC) diversity in Tasmanian devils. RESULTS Here we report the characterization of the genomic regions encompassing MHC Class I and Class II genes in the Tasmanian devil. Four genomic regions approximately 960 kb in length were assembled and annotated using BAC contigs and physically mapped to devil Chromosome 4q. 34 genes and pseudogenes were identified, including five Class I and four Class II loci. Interestingly, when two haplotypes from two individuals were compared, three genomic copy number variants with sizes ranging from 1.6 to 17 kb were observed within the classical Class I gene region. One deletion is particularly important as it turns a Class Ia gene into a pseudogene in one of the haplotypes. This deletion explains the previously observed variation in the Class I allelic number between individuals. The frequency of this deletion is highest in the northwestern devil population and lowest in southeastern areas. CONCLUSIONS The third sequenced marsupial MHC provides insights into the evolution of this dynamic genomic region among the diverse marsupial species. The two sequenced devil MHC haplotypes revealed three copy number variations that are likely to significantly affect immune response and suggest that future work should focus on the role of copy number variations in disease susceptibility in this species.This work was funded by an ARC Future Fellowship to KB (FT0992212), the Eric Guiler fund and the Tasmanian Department of Primary Industries, Parks, Water and the Environment. YC was supported by an Endeavour International Postgraduate Research Scholarship, KM by an Australian Postgraduate Award and an ARC Linkage Grant

    Physical activity when young provides lifelong benefits to cortical bone size and strength in men

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    The skeleton shows greatest plasticity to physical activity-related mechanical loads during youth but is more at risk for failure during aging. Do the skeletal benefits of physical activity during youth persist with aging? To address this question, we used a uniquely controlled cross-sectional study design in which we compared the throwing-to-nonthrowing arm differences in humeral diaphysis bone properties in professional baseball players at different stages of their careers (n = 103) with dominant-to-nondominant arm differences in controls (n = 94). Throwing-related physical activity introduced extreme loading to the humeral diaphysis and nearly doubled its strength. Once throwing activities ceased, the cortical bone mass, area, and thickness benefits of physical activity during youth were gradually lost because of greater medullary expansion and cortical trabecularization. However, half of the bone size (total cross-sectional area) and one-third of the bone strength (polar moment of inertia) benefits of throwing-related physical activity during youth were maintained lifelong. In players who continued throwing during aging, some cortical bone mass and more strength benefits of the physical activity during youth were maintained as a result of less medullary expansion and cortical trabecularization. These data indicate that the old adage of “use it or lose it” is not entirely applicable to the skeleton and that physical activity during youth should be encouraged for lifelong bone health, with the focus being optimization of bone size and strength rather than the current paradigm of increasing mass. The data also indicate that physical activity should be encouraged during aging to reduce skeletal structural decay

    Cortical and trabecular bone benefits of mechanical loading are maintained long term in mice independent of ovariectomy.

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    Skeletal loading enhances cortical and trabecular bone properties. How long these benefits last after loading cessation remains an unresolved, clinically relevant question. This study investigated long-term maintenance of loading-induced cortical and trabecular bone benefits in female C57BL/6 mice and the influence of a surgically induced menopause on the maintenance. Sixteen-week-old animals had their right tibia extrinsically loaded 3 days/week for 4 weeks using the mouse tibial axial compression loading model. Left tibias were not loaded and served as internal controls. Animals were subsequently detrained (restricted to cage activities) for 0, 4, 8, 26, or 52 weeks, with ovariectomy (OVX) or sham-OVX surgery being performed at 0 weeks detraining. Loading increased midshaft tibia cortical bone mass, size, and strength, and proximal tibia bone volume fraction. The cortical bone mass, area, and thickness benefits of loading were lost by 26 weeks of detraining because of heightened medullary expansion. However, loading-induced benefits on bone total area and strength were maintained at each detraining time point. Similarly, the benefits of loading on bone volume fraction persisted at all detraining time points. The long-term benefits of loading on both cortical and trabecular bone were not influenced by a surgically induced menopause because there were no interactions between loading and surgery. However, OVX had independent effects on cortical bone properties at early (4 and 8 weeks) detraining time points and trabecular bone properties at all detraining time points. These cumulative data indicate loading has long-term benefits on cortical bone size and strength (but not mass) and trabecular bone morphology, which are not influenced by a surgically induced menopause. This suggests skeletal loading associated with physical activity may provide long-term benefits by preparing the skeleton to offset both the cortical and trabecular bone changes associated with aging and menopause

    Antigen-presenting genes and genomic copy number variations in the Tasmanian devil MHC.

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    RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: The Tasmanian devil (Sarcophilus harrisii) is currently under threat of extinction due to an unusual fatal contagious cancer called Devil Facial Tumour Disease (DFTD). DFTD is caused by a clonal tumour cell line that is transmitted between unrelated individuals as an allograft without triggering immune rejection due to low levels of Major Histocompatibility Complex (MHC) diversity in Tasmanian devils. RESULTS: Here we report the characterization of the genomic regions encompassing MHC Class I and Class II genes in the Tasmanian devil. Four genomic regions approximately 960 kb in length were assembled and annotated using BAC contigs and physically mapped to devil Chromosome 4q. 34 genes and pseudogenes were identified, including five Class I and four Class II loci. Interestingly, when two haplotypes from two individuals were compared, three genomic copy number variants with sizes ranging from 1.6 to 17 kb were observed within the classical Class I gene region. One deletion is particularly important as it turns a Class Ia gene into a pseudogene in one of the haplotypes. This deletion explains the previously observed variation in the Class I allelic number between individuals. The frequency of this deletion is highest in the northwestern devil population and lowest in southeastern areas. CONCLUSIONS: The third sequenced marsupial MHC provides insights into the evolution of this dynamic genomic region among the diverse marsupial species. The two sequenced devil MHC haplotypes revealed three copy number variations that are likely to significantly affect immune response and suggest that future work should focus on the role of copy number variations in disease susceptibility in this species

    The effectiveness, safety and cost-effectiveness of cytisine versus varenicline for smoking cessation in an Australian population: a study protocol for a randomized controlled non-inferiority trial

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    Smoking cessation medications are effective but often underutilised because of costs and side effects. Cytisine is a plant-based smoking cessation medication with over 50 years of use in Central and Eastern Europe. While cytisine has been found to be well-tolerated and more effective than nicotine replacement therapy, direct comparison with varenicline have not been conducted. This study evaluates the effectiveness, safety and cost-effectiveness of cytisine compared with varenicline.Two arm, parallel group, randomised, non-inferiority trial, with allocation concealment and blinded outcome assessment.Australian population-based study.Adult daily smokers (N=1266) interested in quitting will be recruited through advertisements and Quitline telephone-based cessation support services.Eligible participants will be randomised (1:1 ratio) to receive either cytisine capsules (25-day supply) or varenicline tablets (12-week supply), prescribed in accordance with the manufacturer's recommended dosing regimen. The medication will be mailed to each participant's nominated residential address. All participants will also be offered standard Quitline behavioural support (up to six 10-12 minute sessions).Assessments will be undertaken by telephone at baseline, 4- and 7-months post-randomisation. Participants will also be contacted twice (two and four weeks post-randomisation) to ascertain adverse events, treatment adherence and smoking status. The primary outcome will be self-reported 6-month continuous abstinence from smoking, verified by carbon monoxide at 7-month follow-up. We will also evaluate the relative safety and cost-effectiveness of cytisine compared with varenicline. Secondary outcomes will include self-reported continuous and 7-day point prevalence abstinence and cigarette consumption at each follow-up interview.If cytisine is as effective as varenicline, its lower cost and natural plant-based composition may make it an acceptable and affordable smoking cessation medication that could save millions of lives worldwide
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