27 results on '"Sale, C"'
Search Results
2. Bone mineral density in high-level endurance runners: Part B—genotype-dependent characteristics
- Author
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Herbert, AJ, Williams, AG, Lockey, SJ, Erskine, RM, Sale, C, Hennis, PJ, Day, SH, Stebbings, GK, Herbert, AJ, Williams, AG, Lockey, SJ, Erskine, RM, Sale, C, Hennis, PJ, Day, SH, and Stebbings, GK
- Abstract
Purpose Inter-individual variability in bone mineral density (BMD) exists within and between endurance runners and non-athletes, probably in part due to differing genetic profiles. Certainty is lacking, however, regarding which genetic variants may contribute to BMD in endurance runners and if specific genotypes are sensitive to environmental factors, such as mechanical loading via training. Method Ten single-nucleotide polymorphisms (SNPs) were identified from previous genome-wide and/or candidate gene association studies that have a functional effect on bone physiology. The aims of this study were to investigate (1) associations between genotype at those 10 SNPs and bone phenotypes in high-level endurance runners, and (2) interactions between genotype and athlete status on bone phenotypes. Results Female runners with P2RX7 rs3751143 AA genotype had 4% higher total-body BMD and 5% higher leg BMD than AC+CC genotypes. Male runners with WNT16 rs3801387 AA genotype had 14% lower lumbar spine BMD than AA genotype non-athletes, whilst AG+GG genotype runners also had 5% higher leg BMD than AG+GG genotype non-athletes. Conclusion We report novel associations between P2RX7 rs3751143 genotype and BMD in female runners, whilst differences in BMD between male runners and non-athletes with the same WNT16 rs3801387 genotype existed, highlighting a potential genetic interaction with factors common in endurance runners, such as high levels of mechanical loading. These findings contribute to our knowledge of the genetic associations with BMD and improve our understanding of why some runners have lower BMD than others.
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- 2022
3. Beta-alanine did not improve high-intensity performance throughout simulated road cycling
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Perim, P, Gobbi, N, Duarte, B, Oliveira, LFD, Costa, LAR, Sale, C, Gualano, B, Dolan, E, Saunders, B, Perim, P, Gobbi, N, Duarte, B, Oliveira, LFD, Costa, LAR, Sale, C, Gualano, B, Dolan, E, and Saunders, B
- Abstract
This study investigated the effect of beta-alanine supplementation on short-duration sprints and final 4-km simulated uphill cycling time-trial performance during a comprehensive and novel exercise protocol representative of the demands of road-race cycling, and determined if changes were related to increases in muscle carnosine content. Seventeen cyclists (age 38 ± 9 y, height 1.76 ± 0.07 m, body mass 71.4 ± 8.8 kg, V̇O2max 52.4 ± 8.3 ml·kg−1·min−1) participated in this placebo-controlled, double-blind study. Cyclists undertook a prolonged intermittent cycling protocol lasting 125 min, with a 10-s sprint every 20 min, finishing with a 4-km time-trial at 5% simulated incline. Participants completed two familiarization sessions, and two main sessions, one pre-supplementation and one post-supplementation following 28 days of 6.4 g·day−1 of beta-alanine (N=11) or placebo (N=6; maltodextrin). Muscle biopsies obtained pre- and post-supplementation were analysed for muscle carnosine content. There were no main effects on sprint performance throughout the intermittent cycling test (all P>0.05). There was no group (P=0.69), time (P=0.50) or group x time interaction (P=0.26) on time-to-complete the 4-km time-trial. Time-to-completion did not change from pre- to post-supplementation for BA (−19.2 ± 45.6 s, P=0.43) or PL (+2.8 ± 31.6 s, P=0.99). Beta-alanine supplementation increased muscle carnosine content from pre- to post-supplementation (+9.4 ± 4.0 mmol·kg−1dm; P<0.0001) but was not related to performance changes (r=0.320, P=0.37). Chronic beta-alanine supplementation increased muscle carnosine content but did not improve short-duration sprint performance throughout simulated road race cycling, nor 4-km uphill time-trial performance conducted at the end of this cycling test. Highlights Performance during prolonged cycling events often depends on the ability to maintain an increased power output during higher intensity periods. Thus, cyclists are likely heavily dependent o
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- 2022
4. Correction to: Bone mineral density in high-level endurance runners: part A—site-specific characteristics
- Author
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Herbert, AJ, Williams, AG, Lockey, SJ, Erskine, RM, Sale, C, Hennis, PJ, Day, SH, Stebbings, GK, Herbert, AJ, Williams, AG, Lockey, SJ, Erskine, RM, Sale, C, Hennis, PJ, Day, SH, and Stebbings, GK
- Abstract
The original version of this article unfortunately contained a mistake. Figure 1C was missing The corrected Fig. 1 should have appeared as shown in the following page. The original article has been corrected.
- Published
- 2022
5. Bone mineral density in high-level endurance runners: Part B—genotype-dependent characteristics
- Author
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Herbert, AJ, Williams, AG, Lockey, SJ, Erskine, RM, Sale, C, Hennis, PJ, Day, SH, Stebbings, GK, Herbert, AJ, Williams, AG, Lockey, SJ, Erskine, RM, Sale, C, Hennis, PJ, Day, SH, and Stebbings, GK
- Abstract
Purpose Inter-individual variability in bone mineral density (BMD) exists within and between endurance runners and non-athletes, probably in part due to differing genetic profiles. Certainty is lacking, however, regarding which genetic variants may contribute to BMD in endurance runners and if specific genotypes are sensitive to environmental factors, such as mechanical loading via training. Method Ten single-nucleotide polymorphisms (SNPs) were identified from previous genome-wide and/or candidate gene association studies that have a functional effect on bone physiology. The aims of this study were to investigate (1) associations between genotype at those 10 SNPs and bone phenotypes in high-level endurance runners, and (2) interactions between genotype and athlete status on bone phenotypes. Results Female runners with P2RX7 rs3751143 AA genotype had 4% higher total-body BMD and 5% higher leg BMD than AC+CC genotypes. Male runners with WNT16 rs3801387 AA genotype had 14% lower lumbar spine BMD than AA genotype non-athletes, whilst AG+GG genotype runners also had 5% higher leg BMD than AG+GG genotype non-athletes. Conclusion We report novel associations between P2RX7 rs3751143 genotype and BMD in female runners, whilst differences in BMD between male runners and non-athletes with the same WNT16 rs3801387 genotype existed, highlighting a potential genetic interaction with factors common in endurance runners, such as high levels of mechanical loading. These findings contribute to our knowledge of the genetic associations with BMD and improve our understanding of why some runners have lower BMD than others.
- Published
- 2022
6. Bone mineral density in high-level endurance runners: part A—site-specific characteristics
- Author
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Herbert, AJ, Williams, AG, Lockey, SJ, Erskine, RM, Sale, C, Hennis, PJ, Day, SH, Stebbings, GK, Herbert, AJ, Williams, AG, Lockey, SJ, Erskine, RM, Sale, C, Hennis, PJ, Day, SH, and Stebbings, GK
- Abstract
Purpose Physical activity, particularly mechanical loading that results in high-peak force and is multi-directional in nature, increases bone mineral density (BMD). In athletes such as endurance runners, this association is more complex due to other factors such as low energy availability and menstrual dysfunction. Moreover, many studies of athletes have used small sample sizes and/or athletes of varying abilities, making it difficult to compare BMD phenotypes between studies. Method The primary aim of this study was to compare dual-energy X-ray absorptiometry (DXA) derived bone phenotypes of high-level endurance runners (58 women and 45 men) to non-athletes (60 women and 52 men). Our secondary aim was to examine the influence of menstrual irregularities and sporting activity completed during childhood on these bone phenotypes. Results Female runners had higher leg (4%) but not total body or lumbar spine BMD than female non-athletes. Male runners had lower lumbar spine (9%) but similar total and leg BMD compared to male non-athletes, suggesting that high levels of site-specific mechanical loading was advantageous for BMD in females only and a potential presence of reduced energy availability in males. Menstrual status in females and the number of sports completed in childhood in males and females had no influence on bone phenotypes within the runners. Conclusion Given the large variability in BMD in runners and non-athletes, other factors such as variation in genetic makeup alongside mechanical loading probably influence BMD across the adult lifespan.
- Published
- 2021
7. The effects of short-term low energy availability, achieved through diet or exercise, on cognitive function in oral contraceptive users and eumenorrheic women
- Author
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Martin, D, Papageorgiou, M, Colgan, H, Bandelow, S, Greeves, JP, Tang, JCY, Fraser, WD, Cooper, SB, Sale, C, Elliott-Sale, K, Martin, D, Papageorgiou, M, Colgan, H, Bandelow, S, Greeves, JP, Tang, JCY, Fraser, WD, Cooper, SB, Sale, C, and Elliott-Sale, K
- Abstract
To date, no research has explored the effects of low energy availability on cognitive performance using dietary and exercise regimens relevant to athletes. Twenty female participants (10 eumenorrheic, 10 oral contraceptive [OC] users) completed three 3-day conditions: 1) controlled-balanced energy availability without exercise (BAL; 45 kcal·kg lean body mass [LBM]1·day1); 2) diet-induced low energy availability without exercise (DIET; 15 kcal·kg LBM1·day 1); and 3) exercise-induced low energy availability (EX; 15 kcal·kg LBM1·day 1, including 30 kcal·kg LBM1·day 1 treadmill running at 70% maximal oxygen uptake). A cognitive test battery was completed before and after each 3-day condition. Mental rotation test accuracy improved in the BAL condition, but there was a decline in accuracy in the EX condition (BAL, +2.5%; EX, 1.4%; P = 0.042, d = 0.85). DIET (+1.3%) was not different to BAL or EX (P > 0.05). All other measures of cognitive performance were not affected by condition (P > 0.05) and OC use did not affect cognitive responses (P > 0.05). Accuracy in the mental rotation test was impaired when low energy availability was induced through increased exercise energy expenditure. All other aspects of cognition were unaffected by 3 days of low energy availability through diet or exercise. OC use did not mediate the effect of low energy availability on cognition. Novelty: Cognitive function was not affected by 3 days of diet-induced low energy availability. Only spatial awareness was impaired during 3 days of exercise-induced low energy availability. Reproductive hormones affected spatial awareness independent of energy availability.
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- 2021
8. The role of chronic muscle (in)activity on carnosine homeostasis: A study with spinal cord-injured athletes
- Author
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Nemezio, K, de Carvalho Yamaguchi, G, Boito Ramkrapes, AP, Schulz, ML, Baptista, IL, Riani, LA, Gonçalves, LDS, Sale, C, de Medeiros, MHG, Gualano, B, Artioli, GG, Nemezio, K, de Carvalho Yamaguchi, G, Boito Ramkrapes, AP, Schulz, ML, Baptista, IL, Riani, LA, Gonçalves, LDS, Sale, C, de Medeiros, MHG, Gualano, B, and Artioli, GG
- Abstract
To examine the role of chronic (in)activity on muscle carnosine (MCarn) and how chronic (in)activity affects MCarn responses to b-alanine supplementation in spinal cord-injured athletes, 16 male athletes with paraplegia were randomized (2:1 ratio) to receive b-alanine (n = 11) or placebo (PL, n = 5). They consumed 6.4 g/day of b-alanine or PL for 28 days. Muscle biopsies of the active deltoid and the inactive vastus lateralis (VL) were taken before and after supplementation. MCarn in the VL was also compared with the VL of a group of individuals without paraplegia (n = 15). MCarn was quantified in whole muscle and in pools of individual fibers by high-performance liquid chromatography. MCarn was higher in chronically inactive VL vs. well-trained deltoid (32.0 ± 12.0 vs. 20.5 ± 6.1 mmol/kg DM; P = 0.018). MCarn was higher in inactive vs. active VL (32.0 ± 12.0 vs. 21.2 ± 7.5 mmol/kg DM; P = 0.011). In type-I fibers, MCarn was significantly higher in the inactive VL than in the active deltoid (38.3 ± 4.7 vs. 27.3 ± 11.8 mmol/kg DM, P = 0.014). MCarn increased similarly between inactive VL and active deltoid in the b-alanine group (VL: 68.9 ± 55.1%, P = 0.0002; deltoid: 90.5 ± 51.4%, P < 0.0001), with no changes in the PL group. MCarn content was higher in the inactive VL than in the active deltoid and the active VL, but this is probably a consequence of fiber type shift (type I to type II) that occurs with chronic inactivity. Chronically inactive muscle showed an increase in MCarn after BA supplementation equally to the active muscle, suggesting that carnosine accretion following b-alanine supplementation is not influenced by muscle inactivity.
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- 2021
9. A collagen extraction and deuterium oxide stable isotope tracer method for the quantification of bone collagen synthesis rates in vivo
- Author
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Civil, R, Brook, MS, Elliott-Sale, KJ, Santos, L, Varley, I, Lensu, S, Kainulainen, H, Koch, LG, Britton, SL, Wilkinson, DJ, Smith, K, Sale, C, Atherton, PJ, Civil, R, Brook, MS, Elliott-Sale, KJ, Santos, L, Varley, I, Lensu, S, Kainulainen, H, Koch, LG, Britton, SL, Wilkinson, DJ, Smith, K, Sale, C, and Atherton, PJ
- Abstract
The development of safe and practical strategies to prevent weakening of bone tissue is vital, yet attempts to achieve this have been hindered by a lack of understanding of the short-term (days-weeks) physiology of bone collagen turnover. To address this, we have developed a method to quantify bone collagen synthesis in vivo, using deuterium oxide (D2O) tracer incorporation techniques combined with gas chromatography pyrolysis isotope-ratio mass spectrometry (GC-pyrolysis-IRMS). Forty-six male and female rats from a selectively bred model ingested D2O for 3 weeks. Femur diaphyses (FEM), tibia proximal (T-PRO), and distal (T-DIS) epiphyses-metaphyses and tibia mid-shaft diaphyses (T-MID) were obtained from all rats after necropsy. After demineralisation, collagen proteins were isolated and hydrolysed and collagen fractional synthetic rates (FSRs) determined by incorporation of deuterium into protein-bound alanine via GC-pyrolysis-IRMS. The collagen FSR for the FEM (0.131 ± 0.078%/day; 95% CI [0.106–0.156]) was greater than the FSR at T-MID (0.055 ± 0.049%/day; 95% CI [0.040–0.070]; p < 0.001). The T-PRO site had the highest FSR (0.203 ± 0.123%/day; 95% CI [0.166–0.241]) and T-DIS the lowest (0.027 ± 0.015%/day; 95% CI [0.022–0.031]). The three tibial sites exhibited different FSRs (p < 0.001). Herein, we have developed a sensitive method to quantify in vivo bone collagen synthesis and identified site-specific rates of synthesis, which could be applicable to studies of human bone collagen turnover.
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- 2021
10. Histidine dipeptides are key regulators of excitation-contraction coupling in cardiac muscle: evidence from a novel CARNS1 knockout rat model
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Gonçalves, LDS, Sales, LP, Saito, TR, Campos, JC, Fernandes, AL, Natali, J, Jensen, L, Arnold, A, Ramalho, L, Bechara, LRG, Esteca, MV, Correa, I, Sant'Anna, D, Ceroni, A, Michelini, LC, Gualano, B, Teodoro, W, Carvalho, VH, Vargas, BS, Medeiros, MHG, Baptista, IL, Irigoyen, MC, Sale, C, Ferreira, JCB, Artioli, GG, Gonçalves, LDS, Sales, LP, Saito, TR, Campos, JC, Fernandes, AL, Natali, J, Jensen, L, Arnold, A, Ramalho, L, Bechara, LRG, Esteca, MV, Correa, I, Sant'Anna, D, Ceroni, A, Michelini, LC, Gualano, B, Teodoro, W, Carvalho, VH, Vargas, BS, Medeiros, MHG, Baptista, IL, Irigoyen, MC, Sale, C, Ferreira, JCB, and Artioli, GG
- Abstract
Histidine-containing dipeptides (HCDs) are abundantly expressed in striated muscles. Although important properties have been ascribed to HCDs, including H+ buffering, regulation of Ca2+ transients and protection against oxidative stress, it remains unknown whether they play relevant functions in vivo. To investigate the in vivo roles of HCDs, we developed the first carnosine synthase knockout (CARNS1−/−) rat strain to investigate the impact of an absence of HCDs on skeletal and cardiac muscle function. Male wild-type (WT) and knockout rats (4 months-old) were used. Skeletal muscle function was assessed by an exercise tolerance test, contractile function in situ and muscle buffering capacity in vitro. Cardiac function was assessed in vivo by echocardiography and cardiac electrical activity by electrocardiography. Cardiomyocyte contractile function was assessed in isolated cardiomyocytes by measuring sarcomere contractility, along with the determination of Ca2+ transient. Markers of oxidative stress, mitochondrial function and expression of proteins were also evaluated in cardiac muscle. Animals were supplemented with carnosine (1.8% in drinking water for 12 weeks) in an attempt to rescue tissue HCDs levels and function. CARNS1−/− resulted in the complete absence of carnosine and anserine, but it did not affect exercise capacity, skeletal muscle force production, fatigability or buffering capacity in vitro, indicating that these are not essential for pH regulation and function in skeletal muscle. In cardiac muscle, however, CARNS1−/− resulted in a significant impairment of contractile function, which was confirmed both in vivo and ex vivo in isolated sarcomeres. Impaired systolic and diastolic dysfunction were accompanied by reduced intracellular Ca2+ peaks and slowed Ca2+ removal, but not by increased markers of oxidative stress or impaired mitochondrial respiration. No relevant increases in muscle carnosine content were observed after carnosine supplementation. Resu
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- 2021
11. Atrophy Resistant vs. Atrophy Susceptible Skeletal Muscles: “aRaS” as a Novel Experimental Paradigm to Study the Mechanisms of Human Disuse Atrophy
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Bass, JJ, Hardy, EJO, Inns, TB, Wilkinson, DJ, Piasecki, M, Morris, RH, Spicer, A, Sale, C, Smith, K, Atherton, PJ, Phillips, BE, Bass, JJ, Hardy, EJO, Inns, TB, Wilkinson, DJ, Piasecki, M, Morris, RH, Spicer, A, Sale, C, Smith, K, Atherton, PJ, and Phillips, BE
- Abstract
Objective: Disuse atrophy (DA) describes inactivity-induced skeletal muscle loss, through incompletely defined mechanisms. An intriguing observation is that individual muscles exhibit differing degrees of atrophy, despite exhibiting similar anatomical function/locations. We aimed to develop an innovative experimental paradigm to investigate Atrophy Resistant tibialis anterior (TA) and Atrophy Susceptible medial gastrocnemius (MG) muscles (aRaS) with a future view of uncovering central mechanisms. Method: Seven healthy young men (22 ± 1 year) underwent 15 days unilateral leg immobilisation (ULI). Participants had a single leg immobilised using a knee brace and air-boot to fix the leg (75° knee flexion) and ankle in place. Dual-energy X-ray absorptiometry (DXA), MRI and ultrasound scans of the lower leg were taken before and after the immobilisation period to determine changes in muscle mass. Techniques were developed for conchotome and microneedle TA/MG muscle biopsies following immobilisation (both limbs), and preliminary fibre typing analyses was conducted. Results: TA/MG muscles displayed comparable fibre type distribution of predominantly type I fibres (TA 67 ± 7%, MG 63 ± 5%). Following 15 days immobilisation, MG muscle volume (–2.8 ± 1.4%, p < 0.05) and muscle thickness decreased (−12.9 ± 1.6%, p < 0.01), with a positive correlation between changes in muscle volume and thickness (R2 = 0.31, p = 0.038). Importantly, both TA muscle volume and thickness remained unchanged. Conclusion: The use of this unique “aRaS” paradigm provides an effective and convenient means by which to study the mechanistic basis of divergent DA susceptibility in humans, which may facilitate new mechanistic insights, and by extension, mitigation of skeletal muscle atrophy during human DA.
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- 2021
12. Carnosine protects stimulus-secretion coupling through prevention of protein carbonyl adduction events in cells under metabolic stress
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Lavilla, CJ, Billacura, MP, Hanna, K, Boocock, DJ, Coveney, C, Miles, AK, Foulds, GA, Murphy, A, Tan, A, Jackisch, L, Sayers, SR, Caton, PW, Doig, CL, McTernan, PG, Colombo, SL, Sale, C, Turner, MD, Lavilla, CJ, Billacura, MP, Hanna, K, Boocock, DJ, Coveney, C, Miles, AK, Foulds, GA, Murphy, A, Tan, A, Jackisch, L, Sayers, SR, Caton, PW, Doig, CL, McTernan, PG, Colombo, SL, Sale, C, and Turner, MD
- Abstract
Type 2 diabetes is characterised by failure to control glucose homeostasis, with numerous diabetic complications attributable to the resulting exposure of cells and tissues to chronic elevated concentrations of glucose and fatty acids. This, in part, results from formation of advanced glycation and advanced lipidation end-products that are able to modify protein, lipid, or DNA structure, and disrupt normal cellular function. Herein we used mass spectrometry to identify proteins modified by two such adduction events in serum of individuals with obesity, type 2 diabetes, and gestational diabetes, along with similar analyses of human and mouse skeletal muscle cells and mouse pancreatic islets exposed to glucolipotoxic stress. We also report that carnosine, a histidine containing dipeptide, prevented 65–90% of 4-hydroxynonenal and 3-nitrotyrosine adduction events, and that this in turn preserved mitochondrial function and protected stimulus-secretion coupling in cells exposed to metabolic stress. Carnosine therefore offers significant therapeutic potential against metabolic diseases.
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- 2021
13. Effect of menstrual cycle phase, menstrual irregularities and hormonal contraceptive use on anterior knee laxity and non-contact anterior cruciate ligament injury occurrence in women: A protocol for a systematic review and meta-analysis
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Nédélec, E, Foli, E, Shultz, SJ, Swinton, PA, Dolan, E, Enright, K, Piasecki, J, Matthews, JJ, Sale, C, Elliott-Sale, KJ, Nédélec, E, Foli, E, Shultz, SJ, Swinton, PA, Dolan, E, Enright, K, Piasecki, J, Matthews, JJ, Sale, C, and Elliott-Sale, KJ
- Abstract
Exercising women report three to six times more ACL tears than men, which happen, in the majority of cases, with a non-contact mechanism. This sex disparity has, in part, been attributed to the differences in reproductive hormone profiles between men and women. Many studies have shown that anterior knee (AK) laxity and the rate of non-contact ACL injuries vary across the menstrual cycle, but these data are inconsistent. Similarly, several studies have investigated the potential protective effect of hormonal contraceptives on non-contact ACL injuries, but their conclusions are also variable. The purpose of this systematic review and meta-analysis is to, identify, evaluate and summarise the effects of endogenous and exogenous ovarian hormones on AK laxity (primary outcome) and the occurrence of non-contact ACL injuries (secondary outcome) in women. We will perform a systematic search for all observational studies conducted on this topic. Studies will be retrieved by searching electronic databases, clinical trial registers, author’s personal files and cross-referencing selected studies. Risk of bias will be assessed using the Newcastle Ottawa Quality Assessment Scale for Cohort and Case–Control Studies. Certainty in the cumulative evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. The meta-analyses will use a Bayesian approach to address specific research questions in a more intuitive and probabilistic manner. This review is registered on the international database of prospectively registered systematic reviews (PROSPERO; CRD42021252365).
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- 2021
14. Bone mineral density in high-level endurance runners: part A—site-specific characteristics
- Author
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Herbert, AJ, Williams, AG, Lockey, SJ, Erskine, RM, Sale, C, Hennis, PJ, Day, SH, Stebbings, GK, Herbert, AJ, Williams, AG, Lockey, SJ, Erskine, RM, Sale, C, Hennis, PJ, Day, SH, and Stebbings, GK
- Abstract
Purpose Physical activity, particularly mechanical loading that results in high-peak force and is multi-directional in nature, increases bone mineral density (BMD). In athletes such as endurance runners, this association is more complex due to other factors such as low energy availability and menstrual dysfunction. Moreover, many studies of athletes have used small sample sizes and/or athletes of varying abilities, making it difficult to compare BMD phenotypes between studies. Method The primary aim of this study was to compare dual-energy X-ray absorptiometry (DXA) derived bone phenotypes of high-level endurance runners (58 women and 45 men) to non-athletes (60 women and 52 men). Our secondary aim was to examine the influence of menstrual irregularities and sporting activity completed during childhood on these bone phenotypes. Results Female runners had higher leg (4%) but not total body or lumbar spine BMD than female non-athletes. Male runners had lower lumbar spine (9%) but similar total and leg BMD compared to male non-athletes, suggesting that high levels of site-specific mechanical loading was advantageous for BMD in females only and a potential presence of reduced energy availability in males. Menstrual status in females and the number of sports completed in childhood in males and females had no influence on bone phenotypes within the runners. Conclusion Given the large variability in BMD in runners and non-athletes, other factors such as variation in genetic makeup alongside mechanical loading probably influence BMD across the adult lifespan.
- Published
- 2021
15. The interactions of physical activity, exercise and genetics and their associations with bone mineral density: implications for injury risk in elite athletes
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Herbert, AJ, Williams, AG, Hennis, PJ, Erskine, RM, Sale, C, Day, SH, Stebbings, GK, Herbert, AJ, Williams, AG, Hennis, PJ, Erskine, RM, Sale, C, Day, SH, and Stebbings, GK
- Abstract
Low bone mineral density (BMD) is established as a primary predictor of osteoporotic risk and can also have substantial implications for athlete health and injury risk in the elite sporting environment. BMD is a highly multi-factorial phenotype influenced by diet, hormonal characteristics and physical activity. The interrelationships between such factors, and a strong genetic component, suggested to be around 50–85% at various anatomical sites, determine skeletal health throughout life. Genome-wide association studies and case–control designs have revealed many loci associated with variation in BMD. However, a number of the candidate genes identified at these loci have no known associated biological function or have yet to be replicated in subsequent investigations. Furthermore, few investigations have considered gene–environment interactions—in particular, whether specific genes may be sensitive to mechanical loading from physical activity and the outcome of such an interaction for BMD and potential injury risk. Therefore, this review considers the importance of physical activity on BMD, genetic associations with BMD and how subsequent investigation requires consideration of the interaction between these determinants. Future research using well-defined independent cohorts such as elite athletes, who experience much greater mechanical stress than most, to study such phenotypes, can provide a greater understanding of these factors as well as the biological underpinnings of such a physiologically “extreme” population. Subsequently, modification of training, exercise or rehabilitation programmes based on genetic characteristics could have substantial implications in both the sporting and public health domains once the fundamental research has been conducted successfully.
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- 2018
16. The interactions of physical activity, exercise and genetics and their associations with bone mineral density: implications for injury risk in elite athletes
- Author
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Herbert, AJ, Williams, AG, Hennis, PJ, Erskine, RM, Sale, C, Day, SH, Stebbings, GK, Herbert, AJ, Williams, AG, Hennis, PJ, Erskine, RM, Sale, C, Day, SH, and Stebbings, GK
- Abstract
Low bone mineral density (BMD) is established as a primary predictor of osteoporotic risk and can also have substantial implications for athlete health and injury risk in the elite sporting environment. BMD is a highly multi-factorial phenotype influenced by diet, hormonal characteristics and physical activity. The interrelationships between such factors, and a strong genetic component, suggested to be around 50–85% at various anatomical sites, determine skeletal health throughout life. Genome-wide association studies and case–control designs have revealed many loci associated with variation in BMD. However, a number of the candidate genes identified at these loci have no known associated biological function or have yet to be replicated in subsequent investigations. Furthermore, few investigations have considered gene–environment interactions—in particular, whether specific genes may be sensitive to mechanical loading from physical activity and the outcome of such an interaction for BMD and potential injury risk. Therefore, this review considers the importance of physical activity on BMD, genetic associations with BMD and how subsequent investigation requires consideration of the interaction between these determinants. Future research using well-defined independent cohorts such as elite athletes, who experience much greater mechanical stress than most, to study such phenotypes, can provide a greater understanding of these factors as well as the biological underpinnings of such a physiologically “extreme” population. Subsequently, modification of training, exercise or rehabilitation programmes based on genetic characteristics could have substantial implications in both the sporting and public health domains once the fundamental research has been conducted successfully.
- Published
- 2018
17. A Comparative Study of Hummingbirds and Chickens Provides Mechanistic Insight on the Histidine Containing Dipeptide Role in Skeletal Muscle Metabolism
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Dolan, E, Saunders, B, Dantas, W, Murai, I H, Roschel, H, Artioli, G, Harris, R, Bicudo, Jose E, Sale, C, Gualano, B, Dolan, E, Saunders, B, Dantas, W, Murai, I H, Roschel, H, Artioli, G, Harris, R, Bicudo, Jose E, Sale, C, and Gualano, B
- Abstract
Histidine containing dipeptides (HCDs) have numerous ergogenic and therapeutic properties, but their primary role in skeletal muscle remains unclear. Potential functions include pH regulation, protection against reactive oxygen/nitrogen species, or Ca2+regulation. In recognition of the challenge of isolating physiological processes in-vivo, we employed a comparative physiology approach to investigate the primary mechanism of HCD action in skeletal muscle. We selected two avian species (i.e., hummingbirds and chickens), who represented the extremes of the physiological processes in which HCDs are likely to function. Our findings indicate that HCDs are non-essential to the development of highly oxidative and contractile muscle, given their very low content in hummingbird skeletal tissue. In contrast, their abundance in the glycolytic chicken muscle, indicate that they are important in anaerobic bioenergetics as pH regulators. This evidence provides new insights on the HCD role in skeletal muscle, which could inform widespread interventions, from health to elite performance.
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- 2018
18. Associations of bone mineral density-related genes and marathon performance in elite European Caucasian marathon runners.
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Herbert, AJ, Williams, AG, Lockey, SJ, Erskine, RM, Hennis, PJ, Sale, C, Day, SH, Stebbings, GK, Herbert, AJ, Williams, AG, Lockey, SJ, Erskine, RM, Hennis, PJ, Sale, C, Day, SH, and Stebbings, GK
- Abstract
Bone mineral density (BMD) is a multi-factorial phenotype determined by factors such as physical activity, diet and a sizeable genetic component. Athletic populations tend to possess higher BMD than non-athletes due to a larger volume of exercise completed. Despite this, some endurance runners can possess low BMD and/or suffer stress fractures, which can have negative impacts on their health and performance. Therefore, we hypothesised that elite endurance runners would possess a genotype associated with enhanced BMD and a reduced risk of injury, resulting in less training interruption and greater potential success. The study compared the genotype and allele frequencies of 5 genetic variants associated with BMD (LRP5 rs3736228, TNFRSF11B rs4355801, VDR rs2228570, WNT16 rs3801387, AXIN1 rs9921222) in elite (men < 2 h 30 min, n = 110; women < 3 h 00 min, n = 98) and sub-elite (men 2 h 30 min – 2 h 45 min, n = 181; women 3 h 00 min – 3 h 15 min, n = 67) marathon runners with those of a non-athlete control population (n = 474). We also investigated whether marathon personal best time was associated with a more “advantageous” BMD genotype. Congruent with our hypothesis, the “risk” T allele for the AXIN1 rs9921222 polymorphism was 5% more frequent in the control group than in sub-elites (P = 0.030, χ2 = 4.69) but no further differences were observed for this variant (P ≥ 0.083, χ2 ≤ 4.98). WNT16 rs3801387 genotype frequency differed between athletes and controls (P = 0.002, χ2 = 12.02) and elites vs controls (P = 0.008, χ2 = 9.72), as did allele frequency. However, contrary to our hypothesis, it was the “risk” A allele that was ~5% more frequent in athletes than controls. Similarly, when combining data from all 5 variants, the athletes had a lower Total Genotype Score than controls (53.6 vs 65.7; P ≤ 0.001), again suggesting greater genetic susceptibility to bone injury in athletes. Personal best times were not associated with genotype in any comparison. These results sugg
- Published
- 2017
19. Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness
- Author
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Willems, SM, Wright, DJ, Day, FR, Trajanoska, K, Joshi, PK, Morris, JA, Matteini, AM, Garton, FC, Grarup, N, Oskolkov, N, Thalamuthu, A, Mangino, M, Liu, J, Demirkan, A, Lek, M, Xu, L, Wang, G, Oldmeadow, C, Gaulton, KJ, Lotta, LA, Miyamoto-Mikami, E, Rivas, MA, White, T, Loh, P-R, Aadahl, M, Amin, N, Attia, JR, Austin, K, Benyamin, B, Brage, S, Cheng, Y-C, Cieszczyk, P, Derave, W, Eriksson, K-F, Eynon, N, Linneberg, A, Lucia, A, Massidda, M, Mitchell, BD, Miyachi, M, Murakami, H, Padmanabhan, S, Pandey, A, Papadimitriou, L, Rajpal, DK, Sale, C, Schnurr, TM, Sessa, F, Shrine, N, Tobin, MD, Varley, I, Wain, LV, Wray, NR, Lindgren, CM, MacArthur, DG, Waterworth, DM, McCarthy, MI, Pedersen, O, Khaw, K-T, Kie, DP, Pitsiladis, Y, Fuku, N, Franks, PW, North, KN, van Duijn, CM, Mather, KA, Hansen, T, Hansson, O, Spector, T, Murabito, JM, Richards, JB, Rivadeneira, F, Langenberg, C, Perry, JRB, Wareham, NJ, Scott, RA, Willems, SM, Wright, DJ, Day, FR, Trajanoska, K, Joshi, PK, Morris, JA, Matteini, AM, Garton, FC, Grarup, N, Oskolkov, N, Thalamuthu, A, Mangino, M, Liu, J, Demirkan, A, Lek, M, Xu, L, Wang, G, Oldmeadow, C, Gaulton, KJ, Lotta, LA, Miyamoto-Mikami, E, Rivas, MA, White, T, Loh, P-R, Aadahl, M, Amin, N, Attia, JR, Austin, K, Benyamin, B, Brage, S, Cheng, Y-C, Cieszczyk, P, Derave, W, Eriksson, K-F, Eynon, N, Linneberg, A, Lucia, A, Massidda, M, Mitchell, BD, Miyachi, M, Murakami, H, Padmanabhan, S, Pandey, A, Papadimitriou, L, Rajpal, DK, Sale, C, Schnurr, TM, Sessa, F, Shrine, N, Tobin, MD, Varley, I, Wain, LV, Wray, NR, Lindgren, CM, MacArthur, DG, Waterworth, DM, McCarthy, MI, Pedersen, O, Khaw, K-T, Kie, DP, Pitsiladis, Y, Fuku, N, Franks, PW, North, KN, van Duijn, CM, Mather, KA, Hansen, T, Hansson, O, Spector, T, Murabito, JM, Richards, JB, Rivadeneira, F, Langenberg, C, Perry, JRB, Wareham, NJ, and Scott, RA
- Abstract
Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P<5 × 10-8) in combined analyses. A number of these loci contain genes implicated in structure and function of skeletal muscle fibres (ACTG1), neuronal maintenance and signal transduction (PEX14, TGFA, SYT1), or monogenic syndromes with involvement of psychomotor impairment (PEX14, LRPPRC and KANSL1). Mendelian randomization analyses are consistent with a causal effect of higher genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality.
- Published
- 2017
20. Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness
- Author
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Willems, SM, Wright, DJ, Day, FR, Trajanoska, Katerina, Joshi, PK, Morris, JA, Matteini, A M, Garton, FC, Grarup, N, Oskolkov, N, Thalamuthu, A, Mangino, M, Liu, Jun, Demirkan, Ayse, Lek, M, Xu, LW, Wang, G, Oldmeadow, C, Gaulton, KJ, Lotta, LA, Miyamoto-Mikami, E, Rivas, MA, White, T, Loh, PR, Aadahl, M, Amin, Najaf, Attia, JR, Austin, K, Benyamin, B, Brage, S, Cheng, YC, Cieszczyk, P, Derave, W, Eriksson, KF, Eynon, N, Linneberg, A, Lucia, A, Massidda, M, Mitchell, BD, Miyachi, M, Murakami, H, Padmanabhan, S, Pandey, A, Papadimitriou, L, Rajpal, DK, Sale, C, Schnurr, TM, Sessa, F, Shrine, N, Tobin, MD, Varley, I, Wain, LV, Wray, NR, Lindgren, CM, MacArthur, DG, Waterworth, DM, McCarthy, MI, Pedersen, O, Khaw, KT, Kie, DP, Pitsiladis, Y, Fuku, N, Franks, PW, North, KN, Duijn, Cornelia, Mather, KA, Hansen, T, Hansson, O, Spector, T, Murabito, JM, Richards, JB, Rivadeneira, Fernando, Langenberg, C, Perry, JRB, Wareham, NJ, Scott, RA, Willems, SM, Wright, DJ, Day, FR, Trajanoska, Katerina, Joshi, PK, Morris, JA, Matteini, A M, Garton, FC, Grarup, N, Oskolkov, N, Thalamuthu, A, Mangino, M, Liu, Jun, Demirkan, Ayse, Lek, M, Xu, LW, Wang, G, Oldmeadow, C, Gaulton, KJ, Lotta, LA, Miyamoto-Mikami, E, Rivas, MA, White, T, Loh, PR, Aadahl, M, Amin, Najaf, Attia, JR, Austin, K, Benyamin, B, Brage, S, Cheng, YC, Cieszczyk, P, Derave, W, Eriksson, KF, Eynon, N, Linneberg, A, Lucia, A, Massidda, M, Mitchell, BD, Miyachi, M, Murakami, H, Padmanabhan, S, Pandey, A, Papadimitriou, L, Rajpal, DK, Sale, C, Schnurr, TM, Sessa, F, Shrine, N, Tobin, MD, Varley, I, Wain, LV, Wray, NR, Lindgren, CM, MacArthur, DG, Waterworth, DM, McCarthy, MI, Pedersen, O, Khaw, KT, Kie, DP, Pitsiladis, Y, Fuku, N, Franks, PW, North, KN, Duijn, Cornelia, Mather, KA, Hansen, T, Hansson, O, Spector, T, Murabito, JM, Richards, JB, Rivadeneira, Fernando, Langenberg, C, Perry, JRB, Wareham, NJ, and Scott, RA
- Published
- 2017
21. National survey on the practice of radiation therapists in Australia
- Author
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Sale, C., Halkett, Georgia, Cox, J., Sale, C., Halkett, Georgia, and Cox, J.
- Abstract
Introduction: Radiation therapy (RT), like many allied health professions, has lacked professional practice clarity, which until 2008 had not been comprehensively investigated. This manuscript describes the first phase of a three-phase project investigating the current and future practices of radiation therapists (RTs) in Australia. The aim of phase 1 was to define the practice of RTs in Australia. Methods: A quantitative approach was used to gain an understanding of RT practice. A national survey was distributed to RTs in Australia. Descriptive statistics and content analysis were used to analyse the data. RT practice was analysed in relation to core and non-core roles, where non-core roles were further divided into basic and advanced practices. Results: The data from the national survey were representative of the Australian RT population (n = 525). The current practice of RTs is presented in summary tables for each area of work (treatment, planning, simulation, mould room and general). Conclusion: This study provided clarification of RT practice and indicated there was a desire to relinquish administrative roles to focus on RT–specific practice. There was evidence that some advanced roles were currently practiced in Australia; however, there was no structure to support these roles and they were based only on local need. This study identified that the profession needs to consider how they will maintain core RT practice, while encouraging the development of new roles, and whether some roles need to be relinquished.
- Published
- 2016
22. National survey on the practice of radiation therapists in Australia
- Author
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Sale, C., Halkett, Georgia, Cox, J., Sale, C., Halkett, Georgia, and Cox, J.
- Abstract
Introduction: Radiation therapy (RT), like many allied health professions, has lacked professional practice clarity, which until 2008 had not been comprehensively investigated. This manuscript describes the first phase of a three-phase project investigating the current and future practices of radiation therapists (RTs) in Australia. The aim of phase 1 was to define the practice of RTs in Australia. Methods: A quantitative approach was used to gain an understanding of RT practice. A national survey was distributed to RTs in Australia. Descriptive statistics and content analysis were used to analyse the data. RT practice was analysed in relation to core and non-core roles, where non-core roles were further divided into basic and advanced practices. Results: The data from the national survey were representative of the Australian RT population (n = 525). The current practice of RTs is presented in summary tables for each area of work (treatment, planning, simulation, mould room and general). Conclusion: This study provided clarification of RT practice and indicated there was a desire to relinquish administrative roles to focus on RT–specific practice. There was evidence that some advanced roles were currently practiced in Australia; however, there was no structure to support these roles and they were based only on local need. This study identified that the profession needs to consider how they will maintain core RT practice, while encouraging the development of new roles, and whether some roles need to be relinquished.
- Published
- 2016
23. Synchronous prostate and rectal adenocarcinomas irradiation utilising volumetric modulated arc therapy
- Author
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Ng, SP, Thu, T, Moloney, P, Sale, C, Mathlum, M, Ong, G, Lynch, R, Ng, SP, Thu, T, Moloney, P, Sale, C, Mathlum, M, Ong, G, and Lynch, R
- Abstract
Cases of synchronous prostate and colorectal adenocarcinomas have been sporadically reported. There are case reports on patients with synchronous prostate and rectal cancers treated with external beam radiotherapy alone or combined with high-dose rate brachytherapy boost to the prostate. Here, we illustrate a patient with synchronous prostate and rectal cancers treated using the volumetric arc therapy (VMAT) technique. The patient was treated with radical radiotherapy to 50.4 Gy in 28 fractions to the pelvis, incorporating the involved internal iliac node and the prostate. A boost of 24 Gy in 12 fractions was delivered to the prostate only, using VMAT. Treatment-related toxicities and follow-up prostate-specific antigen and carcinoembryonic antigen were collected for data analysis. At 12 months, the patient achieved complete response for both rectal and prostate cancers without significant treatment-related toxicities.
- Published
- 2015
24. Letter in response to 'The conceptual model of advanced practice does include research'
- Author
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Smith, T., Harris, J., Woznitza, N., Maresse, Sharon, Sale, C., Smith, T., Harris, J., Woznitza, N., Maresse, Sharon, and Sale, C.
- Abstract
This letter refutes the suggestion made the authors of other letters to the Editor that the proposed model of the characteristics of advanced practitioners excludes research International Journal of Experimental Pathology
- Published
- 2015
25. Conceptualisation of the characteristics of advanced practitioners in the medical radiation professions
- Author
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Smith, T., Harris, J., Woznitza, N., Maresse, Sharon, Sale, C., Smith, T., Harris, J., Woznitza, N., Maresse, Sharon, and Sale, C.
- Abstract
© 2015 Australian Institute of Radiography and New Zealand Institute of Medical Radiation Technology. Professions grapple with defining advanced practice and the characteristics of advanced practitioners. In nursing and allied health, advanced practice has been defined as 'a state of professional maturity in which the individual demonstrates a level of integrated knowledge, skill and competence that challenges the accepted boundaries of practice and pioneers new developments in health care'. Evolution of advanced practice in Australia has been slower than in the United Kingdom, mainly due to differences in demography, the health system and industrial relations. This article describes a conceptual model of advanced practitioner characteristics in the medical radiation professions, taking into account experiences in other countries and professions. Using the CanMEDS framework, the model includes foundation characteristics of communication, collaboration and professionalism, which are fundamental to advanced clinical practice. Gateway characteristics are: clinical expertise, with high level competency in a particular area of clinical practice; scholarship and teaching, including a masters qualification and knowledge dissemination through educating others; and evidence-based practice, with judgements made on the basis of research findings, including research by the advanced practitioner. The pinnacle of advanced practice is clinical leadership, where the practitioner has a central role in the health care team, with the capacity to influence decision making and advocate for others, including patients. The proposed conceptual model is robust yet adaptable in defining generic characteristics of advanced practitioners, no matter their clinical specialty. The advanced practice roles that evolve to meet future health service demand must focus on the needs of patients, local populations and communities.
- Published
- 2015
26. Australian radiation therapy - Part Two: Reflections of the past, the present, the future
- Author
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Merchant, Susan, Halkett, Georgia, Sale, C., Merchant, Susan, Halkett, Georgia, and Sale, C.
- Abstract
INTRODUCTION: Documentation on the history of Australian radiotherapy is limited. This study provides radiation therapists' (RTs) perspectives of the people, workplace, and work practices in Australian radiotherapy centres from 1960 onwards. It provides a follow-up to our previous study: Australian radiation therapy: An overview – Part one, which outlines the history and development of radiotherapy from conception until present day. METHODS: Four focus groups were conducted on separate occasions in 2010, one in South Australia and three in Victoria, Australia. Participants who worked in radiotherapy were purposively selected to ensure a range of experience, age, and years of work. RESULTS: From a RT perspective, radiotherapy has evolved from a physically demanding ‘hands-on’ work environment, often with unpleasant sights and smells of disease, to a more technology-driven workplace. CONCLUSION: Understanding these changes and their subsequent effects on the role of Australian RTs will assist future directions in advanced role development.
- Published
- 2014
27. Australian radiation therapy: an overview - Part one
- Author
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Merchant, Susan, Halkett, Georgia, Sale, C., Merchant, Susan, Halkett, Georgia, and Sale, C.
- Abstract
Over the last century radiation therapy has developed and improved in many facets of treatment delivery. Radiation therapy is now recognised as an important treatment modality for malignant disease. Continued research and development has gradually changed the general medical opinion of radiation therapy. It is now recommended that more than 50% of all cancer patients receive radiation therapy. Background: The development of radiation therapy personnel in Australia started with doctors’ assistants arising from a practical need in the application of treatment. This assistant role gradually extended to a more technical role and saw the birth of the radiation therapist [originally known as radiotherapy technician; therapy radiographer]. The historical progress of this profession in Australia is important to understand for further role development and enhancement of radiation therapists. It is also significant if the profession is to embrace the changes in medical approaches, particularly in oncology, where a bio-psychosocial model of health is rapidly becoming the preferred approach. Part one outlines the history and development of Australian radiation therapy from the discovery of radiation until today. Part two is a subsequent paper providing discussion of Australian radiation therapists’ perspectives on the radiation therapy workplace and work-practices from 1960 until today.
- Published
- 2011
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