G C Nicholson

University of Queensland , Brisbane, Queensland, Australia

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Publications (122)443.62 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: We explored the effect of using male and female reference data in a male sample to categorise areal bone mineral density (BMD). Using male reference data, a large proportion of fractures arose from osteopenia, whereas using female reference data shifted the fracture burden into normal BMD. The purpose of this study was to describe fracture risk associated with osteopenia and osteoporosis in older men, defined by areal BMD and using cut-points derived from male and female reference data. As part of the Geelong Osteoporosis Study, we followed 619 men aged 60-93 years after BMD assessments (performed 2001-2006) until 2010, fracture, death or emigration. Post-baseline fractures were radiologically confirmed, and proportions of fractures in each BMD category were age-standardised to national profiles. Based on World Health Organization criteria, and using male reference data, 207 men had normal BMD at the femoral neck, 357 were osteopenic and 55 were osteoporotic. Using female reference data, corresponding numbers were 361, 227 and 31. During the study, 130 men died, 15 emigrated and 63 sustained at least one fracture. Using male reference data, most (86.5 %) of the fractures occurred in men without osteoporosis on BMD criteria (18.4 % normal BMD, 68.1 % osteopenia). The pattern differed when female reference data were used; while most fractures arose from men without osteoporosis (88.2 %), the burden shifted from those with osteopenia (34.8 %) to those with normal BMD (53.4 %). Decreasing BMD categories defined increasing risk of fracture. Although men with osteoporotic BMD were at greatest risk, they made a relatively small contribution to the total burden of fractures. Using male reference data, two-thirds of the fractures arose from men with osteopenia. However, using female reference data, approximately half of the fractures arose from those with normal BMD. Using female reference data to define osteoporosis in men does not appear to be the optimal approach.
    Osteoporosis International 11/2013; · 4.04 Impact Factor
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    ABSTRACT: Objective:Osteoarthritis (OA) most commonly affects the patellofemoral compartment of the knee, and is a major cause of pain and disability. Structural changes that evolve prior to the onset of symptoms can be visualised using magnetic resonance imaging (MRI). There is little known information about the role of adiposity on the early structural changes in the patella cartilage in younger, asymptomatic adult females.Methods:One hundred and sixty asymptomatic women (20-49 years) participating in the Geelong Osteoporosis Study underwent knee MRI (2006-8). Weight and body mass index (BMI) were measured 10 years prior (1994-7, baseline) and at the time of MRI (current), with change over the period calculated (current-baseline). Relationships between measures of adiposity and patella cartilage volume and defects were examined.Results:After adjustment for age and patella bone volume, there was a reduction of 13 ml (95% confidence interval (95% CI), -25.7, -0.55) in patella cartilage volume for every 1 unit increase in current BMI, and a reduction of 27 ml (95% CI -52.6, -1.5) per BMI unit increase over 10 years (P=0.04 for both). No significant association was observed between baseline BMI and patella cartilage volume (P=0.16). Increased baseline and current weight and BMI were associated with increased prevalence of patella cartilage defects (all P<0.001).Conclusions:Adiposity and weight gain during midlife are associated with detrimental structural change at the patella in young to middle-aged healthy non-osteoarthritic women. Maintaining a healthy weight and avoiding weight gain in younger asymptomatic women may be important in the prevention of patellofemoral OA.International Journal of Obesity advance online publication, 9 April 2013; doi:10.1038/ijo.2013.42.
    International journal of obesity (2005) 04/2013; · 5.22 Impact Factor
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    ABSTRACT: Abstract OBJECTIVES: There are few Australian data that examine the association between total knee joint replacement (TKR) utilisation and socioeconomic status (SES). This study examined TKR surgeries with a diagnosis of osteoarthritis (OA) performed for residents of Barwon Statistical Division (BSD) for 2006-2007. DESIGN: Cross-sectional. SETTING: BSD, South-eastern Victoria, Australia PARTICIPANTS: All patients who underwent a TKR for OA, 2006-2007, and whose residential postcode was identified as within the BSD of Australia, and for whom SES data were available, were eligible for inclusion. PRIMARY OUTCOME MEASURE: Primary TKR data ascertained from the Australian Orthopaedic Association National Joint Replacement Registry. Residential addresses were matched with the Australian Bureau of Statistics census data, and the Index of Relative Socioeconomic Disadvantage was used to determine SES, categorised into quintiles whereby quintile 1 indicated the most disadvantaged and quintile 5 the least disadvantaged. Age-specific and sex-specific rates of TKR utilisation per 1000 person-years were reported for 10-year age bands. RESULTS: Females accounted for 62.7% of the 691 primary TKR surgeries performed during 2006-2007. The greatest utilisation rates of TKR in males was 7.6 observed in those aged >79 years, and in 10.2 in females observed in those aged 70-79 years. An increase in TKR was observed for males in SES quintile four compared to quintile 1 in which the lowest utilisation which was observed (p=0.04). No differences were observed in females across SES quintiles. CONCLUSIONS: Further investigation is warranted on a larger scale to examine the role that SES may play in TKR utilisation, and to determine whether any social disparities in TKR utilisation reflect health system biases or geographic differences.
    BMJ Open 10/2012; 2(5). · 2.06 Impact Factor
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    ABSTRACT: Heel ultrasound is a more portable modality for assessing fracture risk than dual-energy X-ray absorptiometry and does not use ionising radiation. Fracture risk assessment requires appropriate reference data to enable comparisons. This study reports the first heel ultrasound reference ranges for the Australian population. INTRODUCTION: This study aimed to develop calcaneal (heel) ultrasound reference ranges for the Australian adult population using a population-based random sample. METHODS: Men and women aged ≥20 years were randomly selected from the Barwon Statistical Division in 2001-2006 and 1993-1997, respectively, using the electoral roll. Broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI) were measured at the heel using a Lunar Achilles Ultrasonometer. Gender-specific means and standard deviations for BUA, SOS and SI were calculated for the entire sample (men 20-93 years, n = 1,104; women 20-92 years, n = 914) and for participants aged 20-29 years (men, n = 157; women, n = 151). Associations between ultrasound measures and age were examined using linear regression. RESULTS: For men, mean ± standard deviation BUA, SOS and SI were 118.7 ± 15.8 dB/MHz, 1,577.0 ± 43.7 m/s and 100.5 ± 20.7, respectively; values for women were consistently lower (111.0 ± 16.4 dB/MHz, P < 0.001; 1,571.0 ± 39.0 m/s, P = 0.001; and 93.7 ± 20.3, P < 0.001, respectively). BUA was higher in young men compared with young women (124.5 ± 14.4 vs 121.0 ± 15.1 dB/MHz), but SOS (1,590.1 ± 43.1 vs 1,592.5 ± 35.0 m/s) and SI (108.0 ± 19.9 vs 106.3 ± 17.7) were not. The relationships between age and each ultrasound measure were linear and negative across the age range in men; associations were also negative in women but non-linear. CONCLUSION: These data provide reference standards to facilitate the assessment of fracture risk in an Australian population using heel ultrasound.
    Osteoporosis International 07/2012; · 4.04 Impact Factor
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    ABSTRACT: The association between osteoporosis and osteoarthritis (OA) is controversial. Although previous studies have shown total body, lower limb, spinal and knee BMD and knee cartilage volume to be positively associated, the relationship between other distant site-specific measures of BMD and other knee structures is unknown. The aim of this study was to determine the associations between BMD at eight skeletal sites, and knee structure in asymptomatic young to middle-aged females without any clinical signs of OA. One hundred and sixty healthy, asymptomatic females (29-50 yr) underwent magnetic resonance imaging of the knee. BMD was measured at the spine, hip, total body and forearm by dual energy X-ray absorptiometry, and at the calcaneus by quantitative ultrasound. BMD was tested for an association with cartilage volume, defects, and bone marrow lesions (BMLs). Medial cartilage volume was positively associated with BMD at the spine, total body, femoral neck, and Ward's triangle (all p<0.05), with non-significant associations in the same direction at the trochanter (p=0.07). Findings in the lateral compartment were similar. The presence of medial cartilage knee defects were also associated with BMD at the spine; defects in the lateral compartment were associated with BMD at the forearm (both p=0.05). BMD was not associated with the presence of BMLs. No associations were observed with calcaneus BMD. Site-specific BMD is associated with cartilage volume at the knee in asymptomatic young to middle-aged adults, with the direction and effects trending in the same direction. The magnitude of changes correlates with clinically relevant changes. QUS defined calcaneus BMD, showed no associations with knee structure. Although systemic factors may underlie the association between knee cartilage volume and axial/lower limb BMD, these data suggest that common local, possibly biomechanical factors may also play a role.
    Bone 06/2011; 49(4):839-44. · 4.46 Impact Factor
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    ABSTRACT: Paget's disease of bone (PDB) is a common disorder characterized by focal abnormalities of bone remodeling. We previously identified variants at the CSF1, OPTN and TNFRSF11A loci as risk factors for PDB by genome-wide association study. Here we extended this study, identified three new loci and confirmed their association with PDB in 2,215 affected individuals (cases) and 4,370 controls from seven independent populations. The new associations were with rs5742915 within PML on 15q24 (odds ratio (OR) = 1.34, P = 1.6 × 10(-14)), rs10498635 within RIN3 on 14q32 (OR = 1.44, P = 2.55 × 10(-11)) and rs4294134 within NUP205 on 7q33 (OR = 1.45, P = 8.45 × 10(-10)). Our data also confirmed the association of TM7SF4 (rs2458413, OR = 1.40, P = 7.38 × 10(-17)) with PDB. These seven loci explained ∼13% of the familial risk of PDB. These studies provide new insights into the genetic architecture and pathophysiology of PDB.
    Nature Genetics 05/2011; · 35.21 Impact Factor
  • Article: Bone Genes
    Expert Opinion on Therapeutic Targets. 03/2011; 1(1).
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    ABSTRACT: Genomewide association studies (GWAS) are a powerful method for identifying genes of small to moderate effect involved in common heritable diseases. A phase 1 GWAS was performed in an Australian and UK cohort of postmenopausal female probands (age 50-85 years) with extreme truncate selection for FN BMD (1.5<|z-score|<4), with 317,000 SNPs genotyped using Illumina HumanHap300 chips. 130 SNPs, selected for further study based on the initial results, were genotyped in families selected from the FAMOS cohort (proband FN or LS BMD z-score <-1, n=429 families including 1286 individuals) using Sequenom MALDI-TOF technology. PLINK was used to test association in the GWA component, and QTDT to test total association controlling for linkage in the confirmation family study. For a range of different genetic models, the phase 1 component of 140 subjects has equivalent power to a cohort study of 850-920 unselected individuals. Overall genotyping success rate was 99.6% in phase 1 and 93.1% in phase 2. No gene achieved genomewide statistical significance in the phase 1 screen (as expected due to small sample size). However, 31 markers achieved p-values of 10-5 to 10-7. One SNP, rs10904952, was associated with FN BMD in both phase 1 (P=0.0021) and phase 2 (P=0.00072) studies. Combining these findings, the overall level of significance for this SNP is 4.86x10-6. This SNP lies in the gene encoding ST8 alpha-n-acetyl-neuraminide alpha-2,8-sialyltransferase 6 (ST8SIA6), a protein that interacts with fetuin-alpha, which controls apatite formation and bone and tissue mineralisation. Four other SNPs lying in ST8SIA6 were associated with FN BMD with p-values of 0.0078-0.00048 in the phase 1 study. This study suggests that polymorphisms of ST8SIA6 influence FN BMD in the general population. Whilst the finding did not achieve genomewide significance in the discovery cohort, association was confirmed in the replication cohort, despite modest study power. A much larger cohort of cases with extreme high and low BMD is being recruited for further studies. If confirmed, ST8SIA6 represents a novel gene associated with BMD. The mechanism underlying the association and its effect on fracture risk have yet to be determined.
    01/2011;
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    ABSTRACT: Emerging evidence indicates that early life exposures influence adult health outcomes and there is cause to hypothesise a role for physical activity (PA) in childhood as a protective factor in adult depression. This study aimed to investigate the association between self-reported levels of PA in childhood and self-reported depressive illness. Lifetime depression and levels of physical activity (low/high) in childhood (<15 yr) were ascertained by self-report in 2152 adults (20-97 yr) participating in an ongoing epidemiological study in south-eastern Australia. Data were collected between 2000 and 2006. In this sample, 141 women (18.9%) and 169 men (12.0%) reported ever having a depressive episode. Low PA in childhood was associated with an increased risk of reporting depression in adulthood (OR=1.70, 95%CI=1.32-2.17, p<0.001). Adjustment for age, gender and adult PA attenuated the relationship somewhat (OR=1.35, 95%CI=1.01-1.78, p=0.04), however further adjustment for SES or country of birth did not affect this relationship. In this community-based study, lower levels of self-reported PA in childhood were associated with a 35% increase in odds for self-reported depression in adulthood. These results are consistent with the hypothesis that lower levels of PA in childhood may be a risk factor for adult depression.
    Journal of science and medicine in sport / Sports Medicine Australia. 12/2010; 14(3):222-6.
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    ABSTRACT: There is an inverse association between socioeconomic status (SES) and most causes of morbidity. Hip fractures pose a significant public health burden on society. However, the association between quintiles of area-based SES and incident hip fractures has not been examined in Australia. Using a comprehensive register of hip fractures for the entire Barwon Statistical Division (BSD), we assessed the association between area-based SES and incident hip fractures over a two-year period in residents aged ≥ 50years. Incident hip fractures were identified using a computerized keyword search of all radiological reports from all the radiological centers serving the BSD. Pathological fractures were excluded. SES was determined by cross-referencing residential addresses with Australian Bureau of Statistics census data and categorized in quintiles based upon the BSD reference range. Homogeneity of population at risk in each SES quintile was tested using chi square comparison. Hip fractures in each quintile and within each age strata for the entire BSD region were defined as rates per 1000 person-years. During 2006-2007, there were 495 hip fractures (336 female). An inverse pattern of association was observed between SES and hip fracture incidence, with a peak in fracture numbers observed in the second quintile of SES, with differences between SES quintiles observed for both females (p = 0.005) and males (p = 0.007). The association between incident hip fractures and quintiles of area-based SES provides evidence that those of greater social disadvantage should be a specific target population for intervention to reduce the burden of hip fracture within Australia.
    Bone 10/2010; 48(3):607-10. · 4.46 Impact Factor
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    ABSTRACT: We aimed to report the prevalence, age-of-onset and comorbidity of mood and anxiety disorders in an age-stratified representative sample of Australian women aged 20 years and over. Mood and anxiety disorders were diagnosed utilising a clinical interview (SCID-I/NP). The lifetime and current prevalence of these disorders was determined from the study population (n = 1095) and standardized to 2006 census data for Australia. Approximately one in three women (34.8%) reported a lifetime history of any mood and/or anxiety disorder, with mood disorders (30.0%) being more prevalent than anxiety disorders (13.5%). Of these, major depression (23.4%), panic disorder (5.5%) and specific phobia (3.5%) were the most common. The lifetime prevalence of other disorders was low (< or =3%). A total of 14.4% of women were identified as having a current mood and/or anxiety disorder, with similar rates of mood (8.9%) and anxiety disorders (8.0%) observed. The median age-of-onset for mood disorders was 27.0 years and 18.5 years for anxiety disorders. This study reports the lifetime and current prevalence of mood and anxiety disorders in the Australian female population. The findings emphasize the extent of the burden of these disorders in the community.
    Australasian Psychiatry 06/2010; 18(3):250-5. · 0.60 Impact Factor
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    ABSTRACT: This study aimed to describe treatment initiation rates for men who had recently sustained a fracture. Most (75.9%) men potentially eligible for subsidised treatment at the time of fracture remained untreated even after a subsequent fracture. This study aimed to describe treatment initiation rates for men who had recently sustained a fracture. The study was conducted as part of the Geelong Osteoporosis Study in south-eastern Australia. Men in the study area who had sustained an incident fracture in the period July 2006 to December 2007 were identified from hospital radiology reports. A self-report questionnaire was sent to eligible participants approximately 12 months after fracture. Respondents were asked for details of medications prescribed for 'osteoporosis/fracture/low bone mass' before and after fracture, and where applicable, reasons for cessation of treatment. We analysed the results for 109 men aged 50 years and older who had sustained fracture in the study period. Most (75.9%) men potentially eligible for subsidised treatment at the time of fracture remained untreated. Of the 87 men who were untreated, nine had osteoporosis at the hip and/or spine and 29 (26.6%) reported having sustained a low trauma prior fracture. Our findings are consistent with previously published data showing low rates of treatment initiation in men eligible for osteoporosis treatment. There appear to be barriers involving participants' and medical practitioners' knowledge, beliefs and attitudes regarding osteoporosis and treatment, as well as in the doctor-patient partnership in osteoporosis management. Establishment of clinical pathways for fracture management beyond orthopaedic care may be one of a range of appropriate responses.
    Osteoporosis International 03/2010; 22(1):249-54. · 4.04 Impact Factor
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    ABSTRACT: A large population-based random sample of Australian white men was used to provide normative bone mineral density (BMD) data at multiple anatomical sites. The femoral neck BMD data are very similar to those obtained in USA non-Hispanic white males participating in the National Health and Nutrition Examination Survey III (NHANES III). The reference ranges will be suitable for similar populations. To provide normative BMD data for Australian men derived from a large population-based random sample. An age-stratified random sample of men was recruited from the Australian electoral rolls (n = 1,467 aged 20-97 years). BMD was quantified at multiple sites using Lunar densitometers. Age-related differences in BMD were best predicted by linear relationships at the spine and hip and by quadratic functions at the whole body and forearm. At the spine, a small age-related increase in mean BMD was observed. Although in the subset with no spinal abnormalities, there was a decrease of 0.003 g/cm(2) per year from age 20. At the hip sites, mean BMD decreased at 0.001-0.006 g/cm(2) per year from age 20. At the forearm and whole body, BMD peaked at 41-47 years. Apart from a small difference in men greater than or equal to 80 years, the Australian femoral neck BMD data are not different to those obtained in USA non-Hispanic white males participating in NHANES III and were generally similar to those of large studies from Canada (CaMos) and Spain. These data supply BMD reference ranges at multiple anatomical sites that will be applicable to white Australian men and similar populations such as USA non-Hispanic white men.
    Osteoporosis International 09/2009; 21(6):909-17. · 4.04 Impact Factor
  • Bone 01/2009; 44. · 4.46 Impact Factor
  • Bone 01/2009; 44. · 4.46 Impact Factor
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    ABSTRACT: The epidemiology and sequelae of morphometric vertebral fracture (MVF) are poorly documented. We found that MVFs of the lower thoracic and lumbar spine were associated with poor quality of life and impaired physical function in men. We recommend that morphometric X-ray absorptiometry be included in routine requests for bone densitometry. Vertebral fractures are sentinel events for osteoporosis. We aimed to compare quality of life and physical function in men with and without MVF. Using morphometric X-ray absorptiometry (T10-L4), MVFs were identified in a random sample of men aged 20-93 years. Moderate and severe wedge, biconcave or compression deformities (>25% reduction in any vertebral height) were classified as MVFs. Of 1,147 men, MVFs were identified in 64. No MVFs were detected for men in their twenties. Prevalence was 1.5% for 30-39 years, 1.4% 40-49 years, 3.2% 50-59 years, 4.7% 60-69 years, 10.0% 70-79 years and 14.6% 80+ years. Among 555 men aged 60+ years, those with MVFs were twice as likely to have quality of life scores in the lowest tertile (age-adjusted OR = 2.35, 95%CI 1.24-4.45). MVFs were associated with lower mean age-adjusted physical activity scores [11.3 (95%CI 9.0-13.8) vs 14.0 (13.2-14.9), P = 0.04] and longer mean age-adjusted 'Up-&-Go' times [9.5 (8.9, 10.1) vs 8.9 (8.8, 9.1) s, P = 0.06]. Despite most men being unaware of their condition, MVFs were associated with poor quality of life and impaired physical function. We recommend that morphometric X-ray absorptiometry be included in routine requests for bone densitometry because detection of MVFs has important implications for osteoporosis management in men.
    Osteoporosis International 10/2008; 20(5):787-92. · 4.04 Impact Factor
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    ABSTRACT: Mutations of SQSTM1 are an important cause of PDB, but other genes remain to be discovered. A major susceptibility locus for PDB was identified on chromosome 10p13 by a genome-wide linkage scan in families of British descent, which accounted for the vast majority of cases not caused by SQSTM1 mutations. Introduction: Paget's disease of bone (PDB) has a strong genetic component, and several susceptibility loci have been identified by genome-wide linkage scans. We previously identified three susceptibility loci for PDB using this approach on chromosomes 5q35, 2q36, and 10p13 in 62 families of mainly British descent, but subsequently, mutations in the SQSTM1 gene were found to be the cause of PDB in 23 families from this cohort. Here we reanalyzed the results of our genome-wide search in families from this cohort who did not have SQSTM1 mutations. Materials and Methods: The study population consisted of 210 individuals from 39 families of predominantly British descent with autosomal dominant inheritance of PDB in whom SQSTM1 mutations had been excluded by mutation screening. The average family size was 5.44 +/- 3.98 (SD) individuals (range, 2-24 individuals). Genotyping was performed using standard techniques with 382 microsatellite markers spaced at an average distance of 9.06 cM throughout the autosomes. Multipoint linkage analysis was performed using the GENEHUNTER program under models of homogeneity and heterogeneity. Results: Multipoint parametric linkage analysis under a model of homogeneity and nonparametric linkage analysis under a model of heterogeneity both showed strong evidence of linkage to a single locus on chromosome lOpl3 (LOD score, +4.08) close to the marker D10S1653 at 41.43cM. No evidence of linkage was detected at the chromosome 2q36 locus previously identified in this population, and linkage to other candidate loci previously implicated in the pathogenesis of PDB was excluded. Conclusions: We conclude that there is an important susceptibility gene for PDB on chromosome 10p13 in families of British descent and find no evidence to support the existence of a susceptibility locus on chromosome 2q36 or other previously identified candidate loci for PDB in this population. The gene that lies within the 10pl3 locus seems to account for the development of PDB in the vast majority of families of British descent who do not carry SQSTM1 mutations.
    Journal of Bone and Mineral Research 02/2008; 23(1):58-63. · 6.13 Impact Factor
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    ABSTRACT: Osteoporosis is a highly heritable disease, with estimates of genetic contribution to variance of BMD up to 80%. Genetic studies aiming to identify loci influencing BMD variation have had little success to date, largely due to inadequate power to detect the genes of small to moderate effect size likely to be involved. Adequately powered genome-wide association studies [GWAS] have successfully identified disease-associated genes in complex polygenic disorders. We performed a GWAS to search for BMD loci.
    01/2008;
  • Journal of Affective Disorders - J AFFECT DISORDERS. 01/2008; 107.
  • J A Pasco, M J Henry, G C Nicholson
    Diabetic Medicine 11/2007; 24(10):1173-4. · 3.24 Impact Factor

Publication Stats

3k Citations
443.62 Total Impact Points

Institutions

  • 2011–2013
    • University of Queensland 
      • Department of Medicine
      Brisbane, Queensland, Australia
  • 1997–2013
    • Deakin University
      • School of Medicine
      Geelong, Victoria, Australia
  • 1991–2013
    • University of Melbourne
      • Department of Medicine
      Melbourne, Victoria, Australia
    • The Queen Elizabeth Hospital
      Tarndarnya, South Australia, Australia
  • 2010
    • Monash University (Australia)
      • Department of Epidemiology and Preventive Medicine
      Melbourne, Victoria, Australia
  • 1992–2008
    • Geelong Hospital
      • Department of Medicine
      Geelong, Victoria, Australia
    • University of Western Australia
      Perth City, Western Australia, Australia
  • 1991–2003
    • Fremantle Hospital and Health Service
      Fremantle, Western Australia, Australia
  • 1985–2003
    • Sir Charles Gairdner Hospital
      Perth City, Western Australia, Australia
  • 2000–2001
    • University of Aberdeen
      Aberdeen, Scotland, United Kingdom
  • 1999
    • Saint Vincent Hospital
      • Department of Medicine
      Worcester, Massachusetts, United States
  • 1996
    • Victoria University Melbourne
      Melbourne, Victoria, Australia
  • 1986–1989
    • Repatriation General Hospital
      Tarndarnya, South Australia, Australia