Bronwyn A Kingwell

University of Melbourne, Melbourne, Victoria, Australia

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Publications (189)1125.9 Total impact

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    ABSTRACT: To examine whether the introduction of intermittent standing bouts during the workday using a height-adjustable workstation can improve subjective levels of fatigue, musculoskeletal discomfort and work productivity relative to seated work.
    Occupational and environmental medicine. 08/2014;
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    ABSTRACT: Recent advances in high-throughput lipid profiling by liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) have made it possible to quantify hundreds of individual molecular lipid species (e.g. fatty acyls, glycerolipids, glycerophospholipids, sphingolipids) in a single experimental run for hundreds of samples. This enables the lipidome of large cohorts of subjects to be profiled to identify lipid biomarkers significantly associated with disease risk, progression and treatment response. Clinically, these lipid biomarkers can be used to construct classification models for the purpose of disease screening or diagnosis. However, the inclusion of a large number of highly correlated biomarkers within a model may reduce classification performance, unnecessarily inflate associated costs of a diagnosis or a screen and reduce the feasibility of clinical translation. An unsupervised feature reduction approach can reduce feature redundancy in lipidomic biomarkers by limiting the number of highly correlated lipids while retaining informative features to achieve good classification performance for various clinical outcomes. Good predictive models based on a reduced number of biomarkers are also more cost effective and feasible from a clinical translation perspective.
    Bioinformatics 06/2014; · 5.32 Impact Factor
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    ABSTRACT: Since the discovery in the 1970s that plasma levels of high-density lipoprotein cholesterol (HDL-C) are inversely associated with cardiovascular outcome, it has been postulated that HDL is anti-atherogenic and that increasing HDL-C levels is a promising therapeutic strategy. However, the recent failure of three orally active, HDL-C-raising agents has introduced considerable controversy, prompting the question of whether increasing the cholesterol cargo of HDL in a non-selective manner is an effective pharmacological approach for the translation of its atheroprotective and vasculoprotective activities. The interrelationships between HDL-C concentration, HDL particle number and levels of diverse HDL particle subpopulations of defined composition are complex, as are their relationships with reverse cholesterol transport and other anti-atherogenic functions. Such complexity highlights the incompleteness of our understanding of the biology of HDL particles. This article examines the HDL hypothesis in molecular and mechanistic terms, focusing on features that have been addressed, those that remain to be tested, and potential new targets for future pharmacological interventions.
    Nature reviews. Drug discovery. 05/2014;
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    ABSTRACT: To compare the effect of 7 h of prolonged sitting on resting blood pressure with a similar duration of sitting combined with intermittent brief bouts of light-intensity or moderate-intensity physical activity.
    Nutrition, metabolism, and cardiovascular diseases: NMCD 05/2014; · 3.52 Impact Factor
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    ABSTRACT: To examine whether reductions in sitting time through alternating 30 minute bouts of sitting and standing can reduce postprandial glucose, insulin and triglyceride responses. Twenty-three overweight/obese sedentary office workers (17 males; 6 females; mean ± SD; age: 48.2 ± 7.9 yrs, BMI: 29.6 ± 4.0 kg/m) undertook two, short-term (5-day) experimental conditions in an equal, randomised (1:1) order. In a simulated office environment, participants performed typical occupational tasks for 8 hours/day while in a: 1) seated work posture (control condition); or, 2) interchanging between a seated and standing work posture every 30 minutes using an electric, height-adjustable workstation (intervention condition). Fasting and postprandial blood samples after a mixed test drink were collected hourly for 4 hours on Day 1 and 5 of each condition to assess serum insulin, plasma glucose and triglycerides. Dietary intake (KJ/d) and physical activity were standardised during each condition. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12611000632998). Following adjustment for time (Day 1 and Day5), incremental area under the analyte time curve (iAUC) differed significantly between conditions for plasma glucose (P=0.007) but not for serum insulin or plasma triglycerides. Adjusted mean glucose iAUC was lowered by 11.1% after the intervention condition (6.38mmol/L·h [CI: 5.04, 7.71] ) relative to the control condition (7.18mmol/L·h [CI: 5.85, 8.52] ). No temporal changes (Day 1 vs Day 5) between conditions were observed. Alternating standing and sitting in 30 minute bouts results in modest beneficial effects on postprandial glucose responses in overweight/obese office workers.
    Medicine and science in sports and exercise 03/2014; · 4.48 Impact Factor
  • Julian W Sacre, Garry L R Jennings, Bronwyn A Kingwell
    Hypertension 02/2014; · 6.87 Impact Factor
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    ABSTRACT: -Currently the relationship between circulating lipids and abdominal aortic aneurysm (AAA) is unclear. We conducted a lipidomic analysis to identify serum lipids associated with AAA presence. Secondary analyses assessed the ability of models incorporating lipidomic features to improve stratification of patient groups with and without AAA beyond traditional risk factors. -Serum lipids were profiled via liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of serum from 161 AAA patients and 168 peripheral artery disease controls. Binary logistic regression was used to identify AAA associated lipids. Classification models were created based on a combination of 1) traditional risk factors only, or 2) lipidomic features and traditional risk factors. Model performance was assessed using receiver operator characteristic (ROC) curves. Three diacylglycerols and 7 triacylglycerols were associated with AAA. Combining lipidomic features with traditional risk factors significantly improved stratification of AAA and PAD groups compared to consideration of traditional risk factors alone (mean area under the ROC curve (95% CI): 0.760 (0.756-0.763) and 0.719 (0.716-0.723) respectively; p<0.05). -A group of linoleic acid containing triacylglycerols and diacylglycerols were significantly associated with AAA presence. Inclusion of lipidomic features in multivariate analyses significantly improved prediction of AAA presence compared to traditional risk factors alone.
    Circulation Cardiovascular Genetics 01/2014; · 6.73 Impact Factor
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    ABSTRACT: We recently reported that ramipril more than doubled walking times in peripheral artery disease patients with intermittent claudication. To conduct exploratory analyses of the effects of ramipril therapy on circulating biomarkers of angiogenesis/arteriogenesis, thrombosis, inflammation and leukocyte adhesion in patients with intermittent claudication. 165 patients with intermittent claudication (mean (SD), 65.3 (6.7) years), were administered ramipril 10mg/d (n=82) or matching placebo (n=83) for 24 weeks, in a randomized, double-blind study. Plasma biomarkers of angiogenesis/arteriogenesis (vascular endothelial growth factor, VEGF-A; fibroblast growth factor, FGF-2), thrombosis (D-dimer; von Willebrand Factor, vWF; thrombin-antithrombin III, TAT), inflammation (high sensitivity C-reactive protein, hsCRP; osteopontin, OPN), and leukocyte adhesion (soluble vascular cell adhesion molecule-1, sVCAM-1; soluble intracellular adhesion molecule-1, sICAM-1) were measured at baseline and 24 weeks. Relative to placebo, ramipril was associated with increases in VEGF-A by 38% (95% CI, 34 to 42%) and FGF-2 by 64% (44 to 85%; P<0.001 for both), and reductions in D-dimer by 24% (-30 to -18%), vWF by 22% (-35 to -9%), TAT by 16% (-19 to -13%), hsCRP by 13% (-14 to -9%), OPN by 12% (-14 to -10%), sVCAM-1 by 14% (-18 to -10%), and sICAM-1 by 15% (-17 to -13 %; all P<0.001). With the exception of vWF all the above changes correlated significantly with the change in maximum walking time (P= 0.02-0.001) in the group treated with ramipril. Ramipril is associated with an increase in biomarkers of angiogenesis/arteriogenesis and reduction in markers of thrombosis, inflammation and leukocyte adhesion. This study informs strategies to improve mobility in patients with intermittent claudication.
    Circulation Research 01/2014; · 11.86 Impact Factor
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    ABSTRACT: Lipidomics has developed rapidly over the past decade to the point where clinical application may soon be possible. Developments including high throughput technologies enable the simultaneous quantification of several hundred lipid species, thereby providing a global assessment of lipid metabolism. Given the key role of lipids in the pathophysiology of diabetes and cardiovascular disease, lipidomics has the potential to: i)significantly improve prediction of future disease risk,ii)inform on mechanisms of disease pathogenesis,iii)identify patient groups responsive to particular therapies andiv)more closely monitor response to therapy. Lipidomic analyses of both whole plasma and lipoprotein subfractions are integral to the current initiative to understand the relationships between lipoprotein composition and function and how these are affected by disease and treatment. This approach will not only aid in appropriate targeting of existing lipid lowering therapies such as statins and fibrates, but will be important in unravelling the controversies surrounding HDL-based therapies which have failed in clinical trials to date. The ultimate utility of lipidomics to clinical practice will depend firstly on the ability of risk prediction models incorporating lipidomic parameters to significantly improve upon conventional clinical risk markers in predicting future disease risk. Secondly, for widespread application, lipidomic-based measurements must be practical and accessible through standard pathology laboratories. This review will cover developments in lipidomics including methodology, bioinformatics/statistics, insights into disease pathophysiology, the effect of therapeutic interventions, the role of large clinical outcome trials in validating lipidomic approaches to patient management and potential applications in clinical practice.
    Pharmacology [?] Therapeutics 01/2014; · 7.79 Impact Factor
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    ABSTRACT: Aim To compare the effect of 7 hours of prolonged sitting on resting blood pressure with a similar duration of sitting combined with intermittent brief bouts of light-intensity or moderate-intensity physical activity. Methods and Results Overweight/obese adults (n = 19; aged 45-65 years) were recruited for a randomized three-treatment crossover trial with a one-week washout between treatments: 1) uninterrupted sitting; 2) sitting with 2 minute bouts of light-intensity walking at 3.2km/hr every 20 minutes; and, 3) sitting with 2 minute bouts of moderate-intensity walking at between 5.8-6.4km/hr every 20 minutes. After an initial 2 hour period seated, participants consumed a test meal (75g carbohydrate, 50g fat) and completed each condition over the next 5 hours. Resting blood pressure was assessed oscillometrically every hour as a single measurement, 5 minutes prior to each activity bout. GEE models were adjusted for sex, age, BMI, fasting blood pressure and treatment order. After adjustment for potential confounding variables, breaking up prolonged sitting with light and moderate-intensity activity breaks was associated with lower systolic blood pressure [light:120 ± 1mmHg (estimated marginal mean ± SEM), P=0.002; moderate: 121 ± 1mmHg, P=0.02], compared to uninterrupted sitting (123 ± 1mmHg). Diastolic blood pressure was also significantly lower during both of the activity conditions (light: 76 ± 1mmHg, P=0.006; moderate: 77 ± 1mmHg, P=0.03) compared to uninterrupted sitting (79 ± 1mmHg). No significant between-condition differences were observed in mean arterial pressure or heart rate. Conclusion Regularly breaking up prolonged sitting may reduce systolic and diastolic blood pressure. Trial Registration Number ACTRN12609000656235 (http://www.anzctr.org.au), Trial Registration Date August 4th 2009
    Nutrition, Metabolism and Cardiovascular Diseases. 01/2014;
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    ABSTRACT: Brown adipose tissue (BAT) is a potential therapeutic target to reverse obesity. The purpose of this study was to determine whether primary precursor cells isolated from human adult subcutaneous white adipose tissue (WAT) can be induced to differentiate in-vitro into adipocytes that express key markers of brown or beige adipose, and whether the expression level of such markers differs between lean and obese young adult males. Adipogenic precursor cells were isolated from lean and obese individuals from subcutaneous abdominal WAT biopsies. Cells were grown to confluence, differentiated for 2.5 weeks then harvested for measurement of gene expression and UCP1 protein. There was no difference between groups with respect to differentiation into adipocytes, as indicated by oil red-O staining, rates of lipolysis, and expression of adipogenic genes (FABP4, PPARG). WAT genes (HOXC9, RB1) were expressed equally in the two groups. Post differentiation, the beige adipose specific genes CITED1 and CD137 were significantly increased in both groups, but classic BAT markers ZIC1 and LHX8 decreased significantly. Cell lines from both groups also equally increased post-differentiation expression of the thermogenic-responsive gene PPARGC1A (PGC-1α). UCP1 gene expression was undetectable prior to differentiation, however after differentiation both gene expression and protein content were increased in both groups and were significantly greater in cultures from lean compared with obese individuals (p<0.05). Human subcutaneous WAT cells can be induced to attain BAT characteristics, but this capacity is reduced in WAT cells from obese individuals.
    PLoS ONE 01/2014; 9(3):e91997. · 3.53 Impact Factor
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    ABSTRACT: Expression of brown adipose tissue (BAT) associated proteins like uncoupling protein 1 (UCP1) in inguinal WAT (iWAT) has been suggested to alter iWAT metabolism. The aim of this study was to investigate the role of interleukin-6 (IL-6) in exercise training and cold exposure-induced iWAT UCP1 expression. The effect of daily intraperitoneal injections of IL-6 (3 ng/g) in C57BL/6 mice for 7 days on iWAT UCP1 expression was examined. In addition, the expression of UCP1 in iWAT was determined in response to 3 days of cold exposure (4°C) and 5 weeks of exercise training in wild type (WT) and whole body IL-6 knockout (KO) mice. Repeated injections of IL-6 in C57BL/6 mice increased UCP1 mRNA but not UCP1 protein content in iWAT. Cold exposure increased iWAT UCP1 mRNA content similarly in IL-6 KO and WT mice, while exercise training increased iWAT UCP1 mRNA in WT mice but not in IL-6 KO mice. Additionally, a cold exposure-induced increase in iWAT UCP1 protein content was blunted in IL-6 KO mice, while UCP1 protein content in iWAT was lower in both untrained and exercise trained IL-6 KO mice than in WT mice. In conclusion, repeated daily increases in plasma IL-6 can increase iWAT UCP1 mRNA content and IL-6 is required for an exercise training-induced increase in iWAT UCP1 mRNA content. In addition IL-6 is required for a full induction of UCP1 protein expression in response to cold exposure and influences the UCP1 protein content iWAT of both untrained and exercise trained animals.
    PLoS ONE 01/2014; 9(1):e84910. · 3.53 Impact Factor
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    ABSTRACT: Children of obese mothers have increased risk of metabolic syndrome as adults. Here we report the effects of a high-fat diet in the absence of maternal obesity at conception on skeletal muscle metabolic and transcriptional profiles of adult male offspring. Female Sprague Dawley rats were fed a diet rich in saturated fat and sucrose [high-fat diet (HFD): 23.5% total fat, 9.83% saturated fat, 20% sucrose wt:wt) or a normal control diet [(CD): 7% total fat, 0.5% saturated fat, 10% sucrose wt:wt) for the 3 wk prior to mating and throughout pregnancy and lactation. Maternal weights were not different at conception; however, HFD-fed dams were 22% heavier than controls during pregnancy. On a normal diet, the male offspring of HFD-fed dams were not heavier than controls but demonstrated features of insulin resistance, including elevated plasma insulin concentration [40.1 ± 2.5 (CD) vs 56.2 ± 6.1 (HFD) mU/L; P = 0.023]. Next generation mRNA sequencing was used to identify differentially expressed genes in the offspring soleus muscle, and gene set enrichment analysis (GSEA) was used to detect coordinated changes that are characteristic of a biological function. GSEA identified 15 upregulated pathways, including cytokine signaling (P < 0.005), starch and sucrose metabolism (P < 0.017), inflammatory response (P < 0.024), and cytokine-cytokine receptor interaction (P < 0.037). A further 8 pathways were downregulated, including oxidative phosphorylation (P < 0.004), mitochondrial matrix (P < 0.006), and electron transport/uncoupling (P < 0.022). Phosphorylation of the insulin signaling protein kinase B was reduced [2.86 ± 0.63 (CD) vs 1.02 ± 0.27 (HFD); P = 0.027] and mitochondrial complexes I, II, and V protein were downregulated by 50-68% (P < 0.005). On a normal diet, the male offspring of HFD-fed dams did not become obese adults but developed insulin resistance, with transcriptional evidence of muscle cytokine activation, inflammation, and mitochondrial dysfunction. These data indicate that maternal overnutrition, even in the absence of prepregnancy obesity, can promote metabolic dysregulation and predispose offspring to type 2 diabetes.
    Journal of Nutrition 12/2013; 144(3):237. · 4.20 Impact Factor
  • Bronwyn A Kingwell, M John Chapman
    Circulation 09/2013; 128(10):1112-21. · 15.20 Impact Factor
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    ABSTRACT: It has been postulated that chronic exposure to high levels of advanced glycation end products (AGEs), in particular from dietary sources, can impair insulin secretion. In the present study, we investigated the cross-sectional relationship between AGEs and acute insulin secretion during an intravenous glucose tolerance test (IVGTT) and following a 75 g oral glucose tolerance test (OGTT) in healthy humans. We report the cross-sectional association between circulating AGE concentrations and insulin secretory function in healthy humans (17 F: 27 M, aged 30 ± 10 years) with a wide range of BMI (24.6-31.0 kg/m(2)). Higher circulating concentrations of AGEs were related to increased first phase insulin secretion during IVGTT (r = 0.43; p < 0.05) and lower 2-h glucose concentrations during OGTT (r = -0.31; p < 0.05). In addition, fasting (r = -0.36; p < 0.05) and 2-h glucose concentrations were negatively related to circulating levels of soluble receptor for AGE (RAGE) isoforms (r = -0.39; p < 0.01). In conclusion, in healthy humans, we show a cross-sectional association between advanced glycation end products and acute insulin secretion during glucose tolerance testing.
    Amino Acids 07/2013; · 3.91 Impact Factor
  • Andrew L Carey, Bronwyn A Kingwell
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    ABSTRACT: Harnessing the considerable capacity of brown adipose tissue (BAT) to consume energy was first proposed as a potential target to control obesity nearly 40 years ago. The plausibility of this approach was, however, questioned due to the prevailing view that BAT was either not present or not functional in adult humans. Recent definitive identification of functional BAT in adult humans as well as a number of important advances in the understanding of BAT biology have reignited interest in BAT as an anti-obesity target. Proof-of-concept evidence demonstrating drug-induced BAT activation provides an important foundation for development of targeted pharmacological approaches with clinical application. This review considers evidence from both human and relevant animal studies to determine whether harnessing BAT for the treatment of obesity via pharmacological intervention is a realistic goal.
    Pharmacology [?] Therapeutics 05/2013; · 7.79 Impact Factor
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    ABSTRACT: Rationale: High-density lipoprotein (HDL) cholesterol elevation via cholesteryl ester transfer protein (CETP) inhibition represents a novel therapy for atherosclerosis, which may also have relevance for type 2 diabetes. Objective: The current study assessed the effects of a CETP inhibitor (CETPi) on postprandial insulin, ex vivo insulin secretion and cholesterol efflux from pancreatic β-cells. Methods and Results: Healthy participants received a daily dose of CETPi (n=10) or placebo (n=15) for 14 days in a randomized, double-blind study. Insulin secretion and cholesterol efflux from MIN6N8 β-cells was determined following incubation with treated plasma. CETP inhibition increased plasma HDL cholesterol, apoAI and postprandial insulin. MIN6N8 β-cells incubated with plasma from CETPi-treated individuals (vs placebo) exhibited an increase in both glucose-stimulated insulin secretion (GSIS) and cholesterol efflux over the 14 day treatment period. Conclusions: CETP inhibition increased postprandial insulin and promoted ex vivo β-cell GSIS, potentially via enhanced β-cell cholesterol efflux.
    Circulation Research 05/2013; · 11.86 Impact Factor
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    ABSTRACT: Abstract Background: High levels of circulating advanced glycation end products (AGEs) can initiate chronic low-grade activation of the immune system (CLAIS) with each of these factors independently associated with cardiovascular (CV) morbidity and mortality. Therefore, our objective was to characterize the relationship between serum AGEs, CLAIS and other risk factors for CV disease in normotensive non-diabetic individuals. Methods: We measured body mass index (BMI), waist-to-hip ratio (WHR), blood pressure, lipid and glucose profile in 44 non-diabetic volunteers (17 female, 27 males). Carboxymethyl-lysine (CML) was measured by ELISA as a marker for circulating AGEs and NF-κB p65 activity as an inflammatory marker by DNA-binding in peripheral blood mononuclear cells lysates (PBMC). Results: Plasma CML concentrations were related to diastolic blood pressure (r=-0.51, p<0.01) independently of age, sex, BMI and WHR (p<0.05). Diastolic blood pressure was also related to NF-κB activity in PBMC (r=0.47, p<0.01) before and after adjustment for age, sex, BMI and WHR (p<0.05). Plasma CML concentrations were related to the pulse pressure before (r=0.42; p<0.05) and after adjustment for age, sex, BMI and waist (p<0.05). Neither CML nor NF-κB activity were related to systolic blood pressure (both p=ns). Plasma CML concentrations were not associated with plasma lipid or glucose concentrations (all p=ns). Conclusions: Plasma AGE levels and NF-κB activity in PBMC were independent determinants of diastolic and pulse pressure in healthy normotensive individuals. This association suggests a role for AGEs in the etiology of hypertension, possibly via the initiation of CLAIS and aortic stiffening.
    Clinical Chemistry and Laboratory Medicine 03/2013; · 3.01 Impact Factor
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    Clinical and Experimental Pharmacology and Physiology 03/2013; 40(3):169-76. · 2.41 Impact Factor
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    ABSTRACT: Excessive sitting has been associated with an elevated risk of vascular conditions, particularly venous thrombosis. Interrupting sitting time with intermittent physical activity can reduce venous stasis; however, impacts on other aspects of thrombogenesis are less understood. PURPOSE: To examine the effects of interrupting sitting time on blood coagulation and blood volume parameters in sedentary, middle-aged, overweight/obese adults (11 men/8 women; 53.8 ± 4.9yrs, BMI: 31.2 ± 4.1 kg.m). METHODS: The randomized three-period, three-treatment acute cross-over trial consisted of: uninterrupted sitting; sitting interrupted by 2 min bouts of either light- or moderate-intensity treadmill walking every 20min. In each trialcondition, blood samples were collected at baseline prior to the consumption of a standardized meal (-2hrs) and post-intervention (5hrs). RESULTS: Plasma fibrinogen increased from baseline with uninterrupted sitting (0.24g.l, [0.13-0.34], P<0.001). Light-intensity but not moderate-intensity activity breaks attenuated the increase by 0.17g.l ([0.01-0.32], P<0.05). There were no between-condition differences in prothrombin time, activated partial thromboplastin time, von Willebrand factor, D-dimer or platelet count. Uninterrupted sitting reduced plasma volume and increased hematocrit, hemoglobin and red-cell count; effects attenuated by both light- and moderate-intensity breaks (P<0.05). White-cell count increased with uninterrupted sitting and further increased with moderate-intensity breaks. Mean platelet volume increased with moderate, but not light-intensity breaks or uninterrupted sitting. CONCLUSIONS: Uninterrupted sitting increased fibrinogen and reduced plasma volume, with associated increases in hemoglobin and hematocrit. Activity breaks attenuated these responses, indicative of an ameliorating influence on the pro-coagulant effects of uninterrupted sitting.
    Medicine and science in sports and exercise 02/2013; · 4.48 Impact Factor

Publication Stats

5k Citations
1,125.90 Total Impact Points

Institutions

  • 2004–2014
    • University of Melbourne
      • Department of Physiology
      Melbourne, Victoria, Australia
  • 2003–2014
    • Baker IDI Heart and Diabetes Institute
      • Diabetic Complications Division
      Melbourne, Victoria, Australia
    • University of Grenoble
      Grenoble, Rhône-Alpes, France
    • RMIT University
      • School of Medical Sciences
      Melbourne, Victoria, Australia
  • 2008–2011
    • National Neuroscience Institute
      • Department of Neurology
      Tumasik, Singapore
    • Singapore General Hospital
      • Department of Neurology
      Tumasik, Singapore
  • 2009
    • National Heart Centre Singapore
      • Cardiology
      Tumasik, Singapore
  • 2004–2009
    • Heart Research Institute
      • Free Radical Group
      Newtown, New South Wales, Australia
  • 2007
    • Université René Descartes - Paris 5
      Lutetia Parisorum, Île-de-France, France
  • 1999–2007
    • Monash University (Australia)
      • Department of Physiology
      Melbourne, Victoria, Australia
  • 1996–2007
    • Alfred Hospital
      • Department of Nuclear Medicine
      Melbourne, Victoria, Australia
  • 1998–2006
    • Baker College, Australia
      Hornsby, New South Wales, Australia
  • 2005
    • University of Western Australia
      Perth City, Western Australia, Australia
  • 1999–2003
    • La Trobe University
      • School of Engineering and Mathematical Sciences
      Melbourne, Victoria, Australia