Dissertations / Theses on the topic 'Total body'

Cette thèse, réalisée en partenariat avec l'Institut Curie et Siemens Healthineers, explore l'utilisation de l'imagerie par tomographie par émission de positrons (TEP) pour le pronostic du cancer, en se concentrant sur les lymphomes non hodgkiniens, en particulier le lymphome folliculaire (FL) et le lymphome diffus à grandes cellules B (DLBCL). Partant de l'hypothèse que les biomarqueurs actuels calculés dans les images TEP sous-utilisent leur richesse en informations, ce travail se concentre sur la recherche de nouveaux biomarqueurs en imagerie TEP corps entier. Une première approche manuelle a permis de valider une caractéristique précédemment identifiée (fragmentation de la tumeur) et d'explorer l'importance pronostique de l'atteinte splénique dans les DLBCL, en constatant que le volume de l'atteinte splénique ne permet pas de stratifier davantage les patients présentant une telle atteinte. Pour dépasser les limites empiriques de la recherche manuelle, une méthode d'identification semi-automatique des caractéristiques a été mise au point. Elle consiste à extraire automatiquement des milliers de biomarqueurs candidats et à les tester à l'aide d'un pipeline de sélection conçu pour trouver des caractéristiques quantifiant de nouvelles informations pronostiques. Les biomarqueurs sélectionnés ont ensuite été analysés et recodés de manière plus simple et plus intuitive. Cette approche a permis d'identifier 22 nouveaux biomarqueurs basés sur l'image, qui reflètent des informations biologiques sur les tumeurs, mais aussi l'état de santé général du patient. Parmi eux, 10 caractéristiques se sont avérées pronostiques à la fois pour les patients atteints de FL que pour ceux souffrant de DLBCL. La thèse aborde également le défi que représente l'utilisation de ces caractéristiques dans la pratique clinique, en proposant le modèle ICARE (Individual Coefficient Approximation for Risk Estimation). Ce modèle d'apprentissage automatique, conçu pour réduire le surapprentissage et améliorer la généralisation, a démontré son efficacité dans le cadre du challenge HECKTOR 2022 visant à prédire le risque de rechute de patients atteints de cancer des voies aérodigestives supérieures à partir de leurs images TEP. Ce modèle s'est également avéré plus résistant au surapprentissage que d'autres méthodes d'apprentissage automatique lors d'une comparaison exhaustive sur un benchmark de 71 jeux de données médicales. Ces développements ont été implémentés dans une extension logicielle d'un prototype développé par Siemens Healthineers
This thesis in partnership with Institut Curie and Siemens Healthineers explores the use of Positron Emission Tomography (PET) for cancer prognosis, focusing on non-Hodgkin lymphomas, especially follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL). Assuming that current biomarkers computed in PET images overlook significant information, this work focuses on the search for new biomarkers in whole-body PET imaging. An initial manual approach validated a previously identified feature (tumor fragmentation) and explored the prognostic significance of splenic involvement in DLBCL, finding that the volume of splenic involvement does not further stratify patients with such an involvement. To overcome the empirical limitations of the manual search, a semi-automatic feature identification method was developed. It consisted in the automatic extraction of thousands of candidate biomarkers and there subsequent testing by a selection pipeline design to identify features quantifying new prognostic information. The selected biomarkers were then analysed and re-encoded in simpler and more intuitive ways. Using this approach, 22 new image-based biomarkers were identified, reflecting biological information about the tumours, but also the overall health status of the patient. Among them, 10 features were found prognostic of both FL and DLBCL patient outcome. The thesis also addresses the challenge of using these features in clinical practice, proposing the Individual Coefficient Approximation for Risk Estimation (ICARE) model. This machine learning model, designed to reduce overfitting and improve generalizability, demonstrated effectiveness in the HECKTOR 2022 challenge for predicting outcomes from head and neck cancer patients [18F]-PET/CT scans. This model was also found to overfit less than other machine learning methods on an exhaustive comparison using a benchmark of 71 medical datasets. All these developments were implemented in a software extension of a prototype developed by Siemens Healthineers

Understanding the relationship between diet, physical activity and health in humans requires accurate measurement of body composition and daily energy expenditure. Stable isotopes provide a means of measuring total body water and daily energy expenditure under free-living conditions. While the use of isotope ratio mass spectrometry (IRMS) for the analysis of 2H (Deuterium) and 18O (Oxygen-18) is well established in the field of human energy metabolism research, numerous questions remain regarding the factors which influence analytical and measurement error using this methodology. This thesis was comprised of four studies with the following emphases. The aim of Study 1 was to determine the analytical and measurement error of the IRMS with regard to sample handling under certain conditions. Study 2 involved the comparison of TEE (Total daily energy expenditure) using two commonly employed equations. Further, saliva and urine samples, collected at different times, were used to determine if clinically significant differences would occur. Study 3 was undertaken to determine the appropriate collection times for TBW estimates and derived body composition values. Finally, Study 4, a single case study to investigate if TEE measures are affected when the human condition changes due to altered exercise and water intake. The aim of Study 1 was to validate laboratory approaches to measure isotopic enrichment to ensure accurate (to international standards), precise (reproducibility of three replicate samples) and linear (isotope ratio was constant over the expected concentration range) results. This established the machine variability for the IRMS equipment in use at Queensland University for both TBW and TEE. Using either 0.4mL or 0.5mL sample volumes for both oxygen-18 and deuterium were statistically acceptable (p>0.05) and showed a within analytical variance of 5.8 Delta VSOW units for deuterium, 0.41 Delta VSOW units for oxygen-18. This variance was used as “within analytical noise” to determine sample deviations. It was also found that there was no influence of equilibration time on oxygen-18 or deuterium values when comparing the minimum (oxygen-18: 24hr; deuterium: 3 days) and maximum (oxygen-18: and deuterium: 14 days) equilibration times. With regard to preparation using the vacuum line, any order of preparation is suitable as the TEE values fall within 8% of each other regardless of preparation order. An 8% variation is acceptable for the TEE values due to biological and technical errors (Schoeller, 1988). However, for the automated line, deuterium must be assessed first followed by oxygen-18 as the automated machine line does not evacuate tubes but merely refills them with an injection of gas for a predetermined time. Any fractionation (which may occur for both isotopes), would cause a slight elevation in the values and hence a lower TEE. The purpose of the second and third study was to investigate the use of IRMS to measure the TEE and TBW of and to validate the current IRMS practices in use with regard to sample collection times of urine and saliva, the use of two TEE equations from different research centers and the body composition values derived from these TEE and TBW values. Following the collection of a fasting baseline urine and saliva sample, 10 people (8 women, 2 men) were dosed with a doubly labeled water does comprised of 1.25g 10% oxygen-18 and 0.1 g 100% deuterium/kg body weight. The samples were collected hourly for 12 hrs on the first day and then morning, midday, and evening samples were collected for the next 14 days. The samples were analyzed using an isotope ratio mass spectrometer. For the TBW, time to equilibration was determined using three commonly employed data analysis approaches. Isotopic equilibration was reached in 90% of the sample by hour 6, and in 100% of the sample by hour 7. With regard to the TBW estimations, the optimal time for urine collection was found to be between hours 4 and 10 as to where there was no significant difference between values. In contrast, statistically significant differences in TBW estimations were found between hours 1-3 and from 11-12 when compared with hours 4-10. Most of the individuals in this study were in equilibrium after 7 hours. The TEE equations of Prof Dale Scholler (Chicago, USA, IAEA) and Prof K.Westerterp were compared with that of Prof. Andrew Coward (Dunn Nutrition Centre). When comparing values derived from samples collected in the morning and evening there was no effect of time or equation on resulting TEE values. The fourth study was a pilot study (n=1) to test the variability in TEE as a result of manipulations in fluid consumption and level of physical activity; the magnitude of change which may be expected in a sedentary adult. Physical activity levels were manipulated by increasing the number of steps per day to mimic the increases that may result when a sedentary individual commences an activity program. The study was comprised of three sub-studies completed on the same individual over a period of 8 months. There were no significant changes in TBW across all studies, even though the elimination rates changed with the supplemented water intake and additional physical activity. The extra activity may not have sufficiently strenuous enough and the water intake high enough to cause a significant change in the TBW and hence the CO2 production and TEE values. The TEE values measured show good agreement based on the estimated values calculated on an RMR of 1455 kcal/day, a DIT of 10% of TEE and activity based on measured steps. The covariance values tracked when plotting the residuals were found to be representative of “well-behaved” data and are indicative of the analytical accuracy. The ratio and product plots were found to reflect the water turnover and CO2 production and thus could, with further investigation, be employed to identify the changes in physical activity.

The objective of this investigation was to identify the appropriate isotopic fractionation factor for total body water (TBW) from ²H₂O enrichment in respiratory water vapor (RW) compared to serum (S), then to use the RW technique to estimate absolute TBW volumes and TBW relative to fat-free body mass (FFB) in three age groups (prepubescent, PP, age = 5-10 y; young adult, YA, age = 22-39 y; older adult, OA age = 65-84 y) of healthy white males and females. The effects of analytical technique (infrared spectrophotometry, IR versus isotope-ratio mass spectrometry, IRMS) and ambient relative humidity on estimates of TBW were also investigated. The composition of the FFB was estimated using a multi-component statistical model (body density, TBW and bone mineral density), and the errors associated with the traditional two-component formula for percent fat from body density were calculated. Our results demonstrated a significant (p < 0.0001) ²H₂O fractionation effect of 0.971 ± 0.005 (mean ± SEM, n = 36) for TBW from RW compared to S. Analysis by IR and IRMS were highly correlated (R² =.999) but IR values were significantly (p < 0.001) higher than IRMS. Deuterium enrichment in RW samples collected at ambient RH (∼20%) was significantly higher (Δ = 20.2 ± 4.5 ppm, mean ± SEM, p < 0.0005) than in RW samples collected at 100% RH, roughly equivalent to a 1.2 L (3.2%) difference in TBW. Total body water relative to FFB mass (W/FFB) was lower (p < 0.01) in YA males (71.0 ± 1.0%) and females (70.2 ± 1.3%) than in PP (boys = 73.1 ± 1.6%; girls = 72.2 ± 1.4%, mean ± SD). In OA, W/FFB was higher (p < 0.05) than in YA (OAM = 72.6 ± 1.1%; OAF = 72.2 ± 1.4%). The density of the FFB was 1.0996 and 1.0839 g/ml in OAM and OAF, respectively. Percent fat from density plus TBW and BMD was lower than from density alone in all groups but YA males, where it was 2.4 percent fat higher. In PP, the Siri density formula resulted in an overestimate of 5.8 ± 2.6 percent fat (mean ± SD, range = 1.4 to 13.6%). In OA females, the density formula overestimated percent fat by 4.4 ± 2.8% (range = 0 to 10.4%). In conclusion, RW corrected for isotopic fractionation will provide acceptable estimates of TBW, although the effects of analytical technique and RH should be controlled. The existence of age-related differences in FFB composition causes errors when the two-component model is used to estimate percent fat in PP and OA females.

This thesis contains work carried out in two separate fields of medical physics. Firstly, an instrument is described which enable orthopaedic surgeons to measure the in vivo sarcomere length in muscle fibre. The technique relies on the diffraction of laser light as it passes through the periodic structure of striated muscle. The resulting instrument is a modification of one described by other workers. Various refinements to the instrument were carried out and tested during several tendon-transfer operations. A precision of 3% in the sarcomere length may be achieved which is adequate for the surgeons needs. Secondly, simulations and experiments were performed to investigate an arcing Total Body Irradiation technique to be used in radiotherapy. The technique was first proposed by workers at Christchurch Hospital and this work continues that study. Computer code was written to simulate the treatment using Monte Carlo methods for radiation transport. Various characteristics of the treatment were examined such as dose rates, dose uniformity and dose compensation. These properties must be known if the treatment is to be implemented in a clinical situation. An anthropomorphic model was used which demonstrates the dose uniformity achievable with this method.

Following a departmental expansion, an isocentric cobalt-60 external beam teletheraphy unit was modified to produce a large fixed field for total body irradiation. The sourcehead was separated from the gantry and installed at a distance of 251.2 cm from the floor. The collimator was removed and replaced with a custom built secondary collimator projecting a 277 x 132.6 cm 2 radiation field at floor level. The work presented in this thesis describes the measurements performed to bring the unit into clinical use for total body irradiation. A custom flattening filter was placed below the secondary collimator to flatten the beam to within +/-3% of the central axis dose as measured at 10 cm in water. Percent depth dose, tissue-phantom-ratios, surface dose and absolute output were measured in the radiation field. The effects of inhomogeneities were studied and the thickness of lead used for lung attenuators was determined. Verification of treatment planning and delivery was performed with an Alderson-Rando anthropomorphic phantom and showed dose uniformity within +/-10% of the prescribed dose when a lead attenuator was used over the lung.

The boundaries of human space exploration continue to expand with new technology and discoveries making it even more important to investigate the effects of space on biological systems. Although humans have explored space in small increments, reproductive studies must be conducted to determine if stable short- or long-term residences for humans can exist in space. This study explored the effects of whole-body proton radiation on uterine smooth muscle known as the myometrium. Two types of mice utilized in this study were C57BL/6 and B6.129S6Cybbtm1Din/J NOX2 knockout mice. C57BL/6 mice are standard laboratory mice that were used to represent the wildtype treatment group (N=18). The B6.129S6Cybbtm1Din/J NOX2 knockout mice have the NADPH Oxidase 2 gene shut off and represented the NOX2 Knockout treatment group (N=18). A third treatment group was made up of half of the C57BL/6 mice and were fed apocynin (N=18). Apocynin has been shown to inhibit NAPDH oxidase production in mice. NADPH Oxidase 2 is involved in the production of deleterious Reactive Oxygen Species (ROS); thus, apocynin should reduce the production of ROS in mice exposed to radiation. Different doses of radiation (0Gy, 0.5Gy, and 2.0Gy) were applied to the myometrium creating three different treatment subgroups within each mouse strain. The mice received 250 MeV protons at an approximate dose rate of 70cGy/ minute. Myometrium tissue was obtained one week following the radiation treatment. The uteri were removed, embedded, sectioned, and stained in hematoxylin and eosin solution. Thickness was determined by taking five measurements each of the outer longitudinal layer length, the inner circular layer length and the total length of both layers of the myometrium for three individual pieces of tissue for each animal. A one-way analysis of variance (ANOVA) was used to determine statistical differences between the groups and subgroups. Wildtype control mice exposed to 2.0Gy (N=5) of radiation had the thickest outer longitudinal layers compared to wildtype mice exposed to 0Gy (N=5) and 0.5Gy (N=6) (p=0.005, p=0). In the apocynin fed and Knockout treatment groups, the subgroups exposed to 0Gy had the thickest layers compared to their respective subgroups exposed to 0.5Gy and 2.0Gy. The apocynin fed mice exposed to 0Gy (N=6) outer longitudinal layer was statistically significantly thicker than the apocynin-fed mice exposed to 0.5Gy (p=0.004; N=6). The inner circular layer of the apocynin-fed mice exposed to 0.5Gy was statistically significantly thicker than the apocynin-fed mice exposed to 2.0Gy (p=0.001; N=6). Amongst the treatment groups, the wildtype control versus the apocynin fed mice exposed to 0Gy showed the apocynin-fed group to have the thicker outer longitudinal layer (p=0.003) and combined layers (p=0.001). Overall, the knockout group showed no statistical difference when compared to the wildtype control group. Further studies are necessary to reduce the possible confounding effect of the estrous cycle in the mice. The different phases of the mice estrus cycle may inadvertently affect the mouse uterine thickness due to the fluctuations in hormones. This study will add to the limited research regarding the female reproductive system in hopes of expanding the knowledge needed to actualize space colonization.

Abstract Despite the clear benefits that resistance training might have in weight management the effects of resistance training on adiposity in sedentary individuals are unsubstantiated. As such, the aim of the study was to determine the effect of resistance training on anthropometric measures of total, central and abdominal adiposity. Twenty-five healthy, sedentary males not on an energy-restricted diet were assigned to a non-exercising control group (CON) (n = 12) or a resistance training group (RES) (n = 13) to determine the effect of 16 weeks of resistance training on anthropometric measures of total, centrally located and abdominal adiposity. Resistance training was prescribed three times weekly using eight exercises for three sets of 15 repetitions at 60% of one-repetition maximum. Resistance training decreased three of the six anthropometric measures of total adiposity and increased body mass and body mass index (BMI). Resistance training had no impact on the measures of centrally located and abdominal adiposity. Body mass and BMI should be used with caution in risk calculations and measures of total adiposity in individuals engaging in resistance training due to this mode of training increasing lean mass (and thus body mass and BMI). Resistance training reduced total adiposity but did not provide an effective stimulus to lower centrally located and abdominal adiposity.

Total body irradiation is the irradiation of the entire patient as a conditioning for bone marrow transplants. The conditioning process involves destroying the bone marrow allowing for repopulation of the donor bone marrow cells, suppression of the immune system to allow stop graft rejection, and to eliminate the cancer cell population within the patient. Studies have been done demonstrating the importance of TBI conditioning for BMT5. A range of TBI treatment techniques exist, this department uses a bi-lateral technique which requires bolus packed around the patient to simplify the geometry of the treatment. This investigation will focus on one technique which involves using a translating bed. This technique effectively scans a radiation beam over the patient as the bed moves through the beam. Other investigations on translating beds concentrated on varying the scan speed to achieve a dose uniformity to within ±5%. The recommendations quote a dose uniformity of +5% and -10% as acceptable⁹. The dose uniformity in these investigations was along the midline in the longitudinal direction only. This investigation varied field size to achieve dose uniformity to within ±2.5% along the midline of an anthropomorphic phantom. The goal was to determine if a dynamic multi-leaf collimator could be used to give a uniform in the transverse direction as well as the longitudinal direction. An advantage of utilizing the DMLC for this treatment is the ability to shield organs at risk, i.e. lungs and kidneys, without requiring resources to produce shielding blocks14. Gafchromic-EBT film18 was used as a dosimeter but gave unreliable results due to the lack of film scanning equipment with an appropriate sensitivity for reading the dose to the film. Scans were simulated using Xio treatment planning software. The results from the simulations gave a more reliable indication of the absorbed dose to the midline of the phantom. The disadvantage of this varying field size technique was the time and complexity involved in creating a treatment plan. Within the Xio software exists a limit on the number of beams allowed to be applied in a single plan. There is a maximum of 99 beams allowed which is not enough for complete coverage of a patient. A way around this is to increase the field sizes and decrease the scan speed. This option was not investigated. The advantage of this technique was the increased dose uniformity (±2.5%) in comparison to the varying scan speed techniques (±5%). This technique also allows the patient to be unencumbered during the treatment making the process more comfortable for them.

Introduction Cachexia is characterised by a marked weight loss and the presence of anorexia, anaemia, and asthenia. Although cachexia is often associated with the presence and growth of tumour and observed in solid tumours of the upper gastrointestinal tract, its presence is not unique to cancer and is often also present in most chronic, end-stage diseases processes. The loss of body fat, altered lipid metabolism, increase in the resting energy expenditure, and the increased loss of body protein the degree of which is associated with poor survival, are all hallmarks of this detrimental disease. The clinical aspects and consequences of cachexia can simply be summarised as morbidity, debilitating conditions, and mortality. The conditions such as loss of muscle mass, impaired muscle function, fatigue, reduced activity and functional capacity by themselves are enough to severely and significantly affect the patients’ QL. Although different interventional procedures and therapies are available for the treatment of cachexia and its symptoms, effective methods to evaluate their benefits and outcomes have not been tested or investigated. It was, therefore, the aim of this project to use body composition analysis as a clinical tool and evaluate the effectiveness and outcome of interventional and therapeutic procedures in three groups of patients with cancer. Methods Three patient groups were investigated: 1) patients with pancreatic cancer undergoing Whipple’s Procedure, 2) patients with pancreatic cancer undergoing cancer chemotherapy and receiving either EPA or placebo, and 3) patients with malignant mesothelioma undergoing cancer chemotherapy plus thalidomide or thalidomide alone. Body composition analysis techniques were used to assess the changes in TBN, TBF, TBK, and TBW. In addition, the body composition parameters together with clinical measures were also used to determine parameters influencing survival. The malignant mesothelioma patients were randomised into patients who received gemcitabine / cisplatin plus thalidomide and those who received thalidomide alone. The pancreatic cancer patients undergoing chemotherapy were randomised into the group who were receiving EPA and those who were receiving placebo. In addition, these patients were also investigated on the basis of their disease extent where they were separated into two groups of metastatic and locally advanced. Unpaired T-Test and ANOVA were used to determine differences between groups. Kaplan-Meier analysis and Cox’s Regression were used to assess survival in all three patient cohorts. The Whipple’s Procedure patients were separated into those who received a Clear Margin and those who received an Unclear Margin during their resection. Results 1) In the pancreatic cancer patients undergoing Whipple’s Procedure, compared to the base-line, there were highly significant changes in Weight (p=0.006), BMI (p=0.005), and FM (p=0.007) followed by significant changes in %BFat (p=0.016), TBK/Ht (p=0.021), LBM (By TBK) (p=0.023), LBM (Van Loan) (p=0.034), and LBM (Segal) (p=0.038) at the 14 week time-point. At the 26 weeks post-operative time point, the only significant changes were in the FM (p=0.012), %BFat (p=0.003), and BMI (p=0.027) parameters. There was also a deviation between the two groups in their TBN, LBM and TBW content observable in a long-term setting and fat content in the relatively shorter-term. Although the Unclear Margin group had lower body composition values, both groups seem to begin to gradually “equalise” around the 14 weeks post-operative time-point. The survival analysis results for the Whipple’s Procedure patients demonstrated that Margin Status (p=0.001), Fat Mass (p=0.003) and Age (p=0.081) were significant and could influence survival. 2) When the second cohort pancreatic cancer patients undergoing chemotherapy were analysed, they were initially separated according to the extent of their disease The results of the analyses of body composition changes between measurement time-points for the each group separately, suggested that the patients with locally advanced disease maintain their Weight, FM, and TBN but are more likely to have a lower TBW by the end of the four month of chemotherapy. However, the patients with metastatic pancreatic cancer maintain their TBW but are more likely to have a decreased fat compartment and a higher FFM. The QL analysis showed that the metastatic group are performing “worse” than the locally advanced group especially in term of their Dyspnoea, Nausea & Vomiting, and Sexuality. In addition, the Karnofsky score showed that the metastatic group are not performing as well as the locally advanced group. Furthermore, for the metastatic group there was an increase in the patients’ pain with a decline in mood and general performance as well as increase in gastrointestinal symptoms. Pain Card scores also showed a general increase for the metastatic group and a general decrease for the locally advanced group. When the pancreatic cancer patients undergoing chemotherapy were separated according to whether they received EPA or placebo, the results demonstrated that firstly, due to the fact that the patients were well randomised, the two groups commenced the trial with similar and statistically non-significantly different body composition parameters. Secondly, the two groups were also found to be statistically not different at their corresponding measurement time-points. And thirdly, the patients receiving placebo compared to those receiving EPA lost more Weight, and FM but less TBW throughout the trial. The TBK/Ht (p=0.044), TBK (p=0.042), and LBM (By TBK) (p=0.042), however, showed statistically significant differences where in all three parameters the EPA showed an increase compared to the base-line (pre-chemotherapy). Results of the survival analysis demonstrated that the use of EPA in this group of pancreatic cancer patients did not provide any benefit. In fact, as it was shown in the Kaplan-Meier plot, the group of patients receiving the EPA had a “worse” survival than the group receiving the placebo. The QL results showed that placebo group improved in their functional scales, but increased their Altered Bowel Habit scores with an increase in the perception of pain and decrease in relief from pain. The EPA group, however, showed a decrease in the Loss of Appetite, Dyspnoea, Pain, Pancreatic Pain, and Fatigue, and improvements in Role Functioning and Sexuality. 3) Results of the malignant mesothelioma patients demonstrated that both study arms show similar weight changes. In addition, body composition measurements indicated that the gemcitabine / cisplatin chemotherapy plus thalidomide group had a greater TBN loss and a greater TBW gain than the thalidomide-alone group. This loss of TBN and gain in TBW looked to be “concealed” in the weight. The results of the survival analysis carried out on the mesothelioma patient group suggested that haemoglobin levels (p=0.001), Age (p=0.007), and NI (p=0.008) are the parameters that can influence the survival of patients with malignant mesothelioma undergoing chemotherapy. Conclusions 1) The trend in body composition changes in the Whipple’s Procedure group showed that, although both groups may start with non-significantly different body composition, they tended to grow closer around the 14 week point indicating that the Clear Margin group may lose more than Unclear Margin group. The implications of these findings, therefore, were that once the most appropriate surgical procedure is performed, an adjuvant therapy regimen (such as chemotherapy) at around 14 weeks may have the most impact on the patient’s overall treatment outcome. 2) When the pancreatic cancer patients were separated by the extent of their disease, the results lead to the conclusion that the patients with locally advanced disease maintain their Weight, FM, and TBN but are more likely to have a lower TBW by the end of the four month of chemotherapy. However, the patients with metastatic pancreatic cancer maintain their TBW but are more likely to have a decreased fat compartment and a higher FFM. The QL analysis concluded that the results may point to a worsening and/or progressing disease which is consistent with classic metastatic disease aetiology. From the results of the pancreatic cancer patients undergoing cancer chemotherapy it was concluded that the use of EPA in this group of pancreatic cancer patients undergoing cancer chemotherapy with gemcitabine results in a non-significant reduction in weight loss, FM loss, and TBW gain with a statistically significant increase in FFM. The results of the survival analysis was, however, contradictory suggesting that patients receiving EPA may have a worse survival than the placebo group. The QL analysis here concluded that that EPA does improve the QL of this group of pancreatic cancer patients. 3) From the malignant mesothelioma group it was concluded that provided that the overall anti-cancer potential of gemcitabine / cisplatin plus thalidomide is comparable with that of thalidomide-alone, then by looking purely from the body composition angle one may be able to suggest the use of thalidomide alone in the treatment of malignant mesothelioma in this group of patients. From the results of the survival analysis, the fact that the Study Arm parameter did not reach statistical significance could indicate that survival in these patients is not affected by the presence or absence of chemotherapy with gemcitabine and cisplatin. The body composition techniques were used here as a tool to monitor changes in various body composition parameters to assess the outcomes, including survival, of the administration of different therapies and interventional procedures in these three groups of cancer patients. For these purposes, these techniques were demonstrated to be an effective and invaluable tool.

Doctor of Philosophy
Introduction Cachexia is characterised by a marked weight loss and the presence of anorexia, anaemia, and asthenia. Although cachexia is often associated with the presence and growth of tumour and observed in solid tumours of the upper gastrointestinal tract, its presence is not unique to cancer and is often also present in most chronic, end-stage diseases processes. The loss of body fat, altered lipid metabolism, increase in the resting energy expenditure, and the increased loss of body protein the degree of which is associated with poor survival, are all hallmarks of this detrimental disease. The clinical aspects and consequences of cachexia can simply be summarised as morbidity, debilitating conditions, and mortality. The conditions such as loss of muscle mass, impaired muscle function, fatigue, reduced activity and functional capacity by themselves are enough to severely and significantly affect the patients’ QL. Although different interventional procedures and therapies are available for the treatment of cachexia and its symptoms, effective methods to evaluate their benefits and outcomes have not been tested or investigated. It was, therefore, the aim of this project to use body composition analysis as a clinical tool and evaluate the effectiveness and outcome of interventional and therapeutic procedures in three groups of patients with cancer. Methods Three patient groups were investigated: 1) patients with pancreatic cancer undergoing Whipple’s Procedure, 2) patients with pancreatic cancer undergoing cancer chemotherapy and receiving either EPA or placebo, and 3) patients with malignant mesothelioma undergoing cancer chemotherapy plus thalidomide or thalidomide alone. Body composition analysis techniques were used to assess the changes in TBN, TBF, TBK, and TBW. In addition, the body composition parameters together with clinical measures were also used to determine parameters influencing survival. The malignant mesothelioma patients were randomised into patients who received gemcitabine / cisplatin plus thalidomide and those who received thalidomide alone. The pancreatic cancer patients undergoing chemotherapy were randomised into the group who were receiving EPA and those who were receiving placebo. In addition, these patients were also investigated on the basis of their disease extent where they were separated into two groups of metastatic and locally advanced. Unpaired T-Test and ANOVA were used to determine differences between groups. Kaplan-Meier analysis and Cox’s Regression were used to assess survival in all three patient cohorts. The Whipple’s Procedure patients were separated into those who received a Clear Margin and those who received an Unclear Margin during their resection. Results 1) In the pancreatic cancer patients undergoing Whipple’s Procedure, compared to the base-line, there were highly significant changes in Weight (p=0.006), BMI (p=0.005), and FM (p=0.007) followed by significant changes in %BFat (p=0.016), TBK/Ht (p=0.021), LBM (By TBK) (p=0.023), LBM (Van Loan) (p=0.034), and LBM (Segal) (p=0.038) at the 14 week time-point. At the 26 weeks post-operative time point, the only significant changes were in the FM (p=0.012), %BFat (p=0.003), and BMI (p=0.027) parameters. There was also a deviation between the two groups in their TBN, LBM and TBW content observable in a long-term setting and fat content in the relatively shorter-term. Although the Unclear Margin group had lower body composition values, both groups seem to begin to gradually “equalise” around the 14 weeks post-operative time-point. The survival analysis results for the Whipple’s Procedure patients demonstrated that Margin Status (p=0.001), Fat Mass (p=0.003) and Age (p=0.081) were significant and could influence survival. 2) When the second cohort pancreatic cancer patients undergoing chemotherapy were analysed, they were initially separated according to the extent of their disease The results of the analyses of body composition changes between measurement time-points for the each group separately, suggested that the patients with locally advanced disease maintain their Weight, FM, and TBN but are more likely to have a lower TBW by the end of the four month of chemotherapy. However, the patients with metastatic pancreatic cancer maintain their TBW but are more likely to have a decreased fat compartment and a higher FFM. The QL analysis showed that the metastatic group are performing “worse” than the locally advanced group especially in term of their Dyspnoea, Nausea & Vomiting, and Sexuality. In addition, the Karnofsky score showed that the metastatic group are not performing as well as the locally advanced group. Furthermore, for the metastatic group there was an increase in the patients’ pain with a decline in mood and general performance as well as increase in gastrointestinal symptoms. Pain Card scores also showed a general increase for the metastatic group and a general decrease for the locally advanced group. When the pancreatic cancer patients undergoing chemotherapy were separated according to whether they received EPA or placebo, the results demonstrated that firstly, due to the fact that the patients were well randomised, the two groups commenced the trial with similar and statistically non-significantly different body composition parameters. Secondly, the two groups were also found to be statistically not different at their corresponding measurement time-points. And thirdly, the patients receiving placebo compared to those receiving EPA lost more Weight, and FM but less TBW throughout the trial. The TBK/Ht (p=0.044), TBK (p=0.042), and LBM (By TBK) (p=0.042), however, showed statistically significant differences where in all three parameters the EPA showed an increase compared to the base-line (pre-chemotherapy). Results of the survival analysis demonstrated that the use of EPA in this group of pancreatic cancer patients did not provide any benefit. In fact, as it was shown in the Kaplan-Meier plot, the group of patients receiving the EPA had a “worse” survival than the group receiving the placebo. The QL results showed that placebo group improved in their functional scales, but increased their Altered Bowel Habit scores with an increase in the perception of pain and decrease in relief from pain. The EPA group, however, showed a decrease in the Loss of Appetite, Dyspnoea, Pain, Pancreatic Pain, and Fatigue, and improvements in Role Functioning and Sexuality. 3) Results of the malignant mesothelioma patients demonstrated that both study arms show similar weight changes. In addition, body composition measurements indicated that the gemcitabine / cisplatin chemotherapy plus thalidomide group had a greater TBN loss and a greater TBW gain than the thalidomide-alone group. This loss of TBN and gain in TBW looked to be “concealed” in the weight. The results of the survival analysis carried out on the mesothelioma patient group suggested that haemoglobin levels (p=0.001), Age (p=0.007), and NI (p=0.008) are the parameters that can influence the survival of patients with malignant mesothelioma undergoing chemotherapy. Conclusions 1) The trend in body composition changes in the Whipple’s Procedure group showed that, although both groups may start with non-significantly different body composition, they tended to grow closer around the 14 week point indicating that the Clear Margin group may lose more than Unclear Margin group. The implications of these findings, therefore, were that once the most appropriate surgical procedure is performed, an adjuvant therapy regimen (such as chemotherapy) at around 14 weeks may have the most impact on the patient’s overall treatment outcome. 2) When the pancreatic cancer patients were separated by the extent of their disease, the results lead to the conclusion that the patients with locally advanced disease maintain their Weight, FM, and TBN but are more likely to have a lower TBW by the end of the four month of chemotherapy. However, the patients with metastatic pancreatic cancer maintain their TBW but are more likely to have a decreased fat compartment and a higher FFM. The QL analysis concluded that the results may point to a worsening and/or progressing disease which is consistent with classic metastatic disease aetiology. From the results of the pancreatic cancer patients undergoing cancer chemotherapy it was concluded that the use of EPA in this group of pancreatic cancer patients undergoing cancer chemotherapy with gemcitabine results in a non-significant reduction in weight loss, FM loss, and TBW gain with a statistically significant increase in FFM. The results of the survival analysis was, however, contradictory suggesting that patients receiving EPA may have a worse survival than the placebo group. The QL analysis here concluded that that EPA does improve the QL of this group of pancreatic cancer patients. 3) From the malignant mesothelioma group it was concluded that provided that the overall anti-cancer potential of gemcitabine / cisplatin plus thalidomide is comparable with that of thalidomide-alone, then by looking purely from the body composition angle one may be able to suggest the use of thalidomide alone in the treatment of malignant mesothelioma in this group of patients. From the results of the survival analysis, the fact that the Study Arm parameter did not reach statistical significance could indicate that survival in these patients is not affected by the presence or absence of chemotherapy with gemcitabine and cisplatin. The body composition techniques were used here as a tool to monitor changes in various body composition parameters to assess the outcomes, including survival, of the administration of different therapies and interventional procedures in these three groups of cancer patients. For these purposes, these techniques were demonstrated to be an effective and invaluable tool.

Studi longitudinali di misura del potassio 40 sono rari. Effettuare tale misura è tuttavia importante nella valutazione dei cambiamenti della composizione corporea con l’età. Lo scopo del lavoro è stato quello di misurare longitudinalmente il potassio 40 e la massa cellulare metabolicamente attiva in maschi. E’ stata effettuate la misura del potassio 40, attraverso un contatore di potassio, ogni anno in 133 maschi di età compresa tra i 20 ed i 66 anni. La massa cellulare metabolicamente attiva (BCM) è stata calcolata con la seguente formula: 0.00833 × TBK (mmol). I risultati mostrano un significativo aumento di soggetti soprappeso ed obesi tra l’ingresso e l’uscita dallo studio. Non c’è stata alcun significativa diminuzione del potassio in questo campione di popolazione. Il picco massimo di BCM è stato riscontrato al di sotto dei 30 anni di età ed era significativo del BMI dopo i 30 anni di età. In conclusione i soggetti con una elevata BCM in età giovanile tendevano ad aumentare il BMI con il passare degli anni.
Background: Longitudinal studies of Total Body Potassium (TBK) are rare. Assessing TBK in order to evaluate Body Cell Mass (BMC) is important in the measure of Body Composition and aging. Objectives: The aim of this study was to assess TBK and BCM in healthy men longitudinally in order to evaluate the changes with age. Design: Longitudinal study Subjects: Body composition of 133 healthy Italian men, 20 to 66 years of age, was measured by whole-body counting of 40K. BCM (kg) was calculated as 0.00833 × TBK (mmol). Results: There was a significant increase in overweight and obese subjects between entry into and exit from the study. There was no significant decrease in TBK in this sample. The maximum BCM score from early age (30 years of age) was found to be a significant predictor of BMI after age 30. Conclusion: Subjects with high maximum BCM at early age tend to increase in BMI as they age.

Total body irradiation (TBI) is often used as part of the conditioning process prior to bone marrow transplants for diseases such as leukemia. By delivering radiation to the entire body, together with chemotherapy, tumour cells are killed and the patient is also immunosupressed. This reduces the risk of disease relapse and increases the chances of a successful implant respectively. TBI requires a large flat field of radiation to cover the entire body with a uniform dose. However, dose uniformity is a major challenge in TBI. (AAPM Report 17) The ICRU report 50 recommends that the dose range within the target volume remain in the range of -5% to +7%. Whilst it is generally accepted that this is not possible for TBI, it is normally clinically acceptable that ±10% of the prescribed dose to the whole body is sufficiently uniform, unless critical structures are being shielded. TBI involves complex dosimetry due to the large source to treatment axis distance (SAD), dose uniformity and flatness over the large field, bolus requirements, extra scatter from the bunker walls and floor and large field overshoot. There is also a lack of specialised treatment planning systems for TBI planning at extended SAD. TBI doses at Westmead Hospital are prescribed to midline. Corrections are made for variations in body contour and tissue density heterogeneity in the lungs using bolus material to increase dose uniformity along midline. Computed tomography (CT) data is imported into a treatment planning system. The CT gives information regarding tissue heterogeneity and patient contour. The treatment planning system uses this information to determine the dose distribution. Using the dose ratio between plans with and without heterogeneity correction the effective chest width can be calculated. The effective chest width is then used for calculating the treatment monitor units and bolus requirements. In this project the tissue heterogeneity corrections from two different treatment planning systems are compared for calculating the effective chest width. The treatment planning systems used were PinnacleTM, a 3D system that uses a convolution method to correct for tissue heterogeneity and calculate dose. The other system, RadplanTM, is a 2D algorithm that corrects for tissue heterogeneity using a modified Batho method and calculates dose using the Bentley - Milan Algorithm. Other possible differences between the treatment planning systems are also discussed. An anthropomorphic phantom was modified during this project. The chest slices were replaced with PerspexTM slices that had different sized cork and PerspexTM inserts to simulate different lung sizes. This allowed the effects of different lung size on the heterogeneity correction to be analysed. The phantom was CT scanned and the information used for the treatment plans. For each treatment planning system and each phantom plans were made with and without heterogeneity corrections. For each phantom the ratio between the plans from each system was used to calculate the effective chest width. The effective chest width was then used to calculate the number of monitor units to be delivered. The calculated dose per monitor unit at the extended TBI distance for the effective chest width from each planning system is then verified using thermoluminescent dosimeters (TLDs) in the unmodified phantom. The original phantom was used for the verification measurements as it had special slots for TLDs. The isodose distributions produced by each planning system are then verified using measurements from Kodak EDR2 radiographic film in the anthropomorphic phantom at isocentre. Further film measurements are made at the extended TBI treatment SAD. It was found that only the width of the lungs made any significant difference to the heterogeneity correction for each treatment planning system. The height and depth of the lungs will affect the dose at the calculation point from changes to the scattered radiation within the volume. However, since the dose from scattered radiation is only a fraction of that from the primary beam, the change in dose was not found to be significant. This is because the calculation point was positioned in the middle of the lungs, so the height and depth of the lungs didn't affect the dose at the calculation point. The dose per monitor unit calculated using the heterogeneity correction for each treatment planning system varied less than the accuracy of the TLD measurements. The isodose distributions measured by film showed reasonable agreement with those calculated by both treatment planning systems at isocentre and a more uniform distribution at the extended TBI treatment distance. The verification measurements showed that either treatment planning system could be used to calculate the heterogeneity correction and hence effective chest width for TBI treatment planning.

Opracowanie metody napromieniania TBI wspomagającej proces leczenia nowotworów układowych, zostało zainicjowane przez rosnące zainteresowanie procedurą TBI lekarzy hematologów z ośrodków zajmujących się transplantacją szpiku kostnego. W tym celu wykorzystano dwa modele megawoltowych akceleratorów liniowych: akcelerator PRIMUS firmy Siemens oraz akcelerator ELEKTA Synergy Platform firmy Elekta. Do terapii wybrane zostały w obu przypadkach wiązki fotonowe o napięciu przyspieszjącym 15 MV oraz wiązki elektronowe o wartości energii, w przedziale od 6 MeV do 15 MeV, dostosowywanej indywidualnie dla każdego pacjenta. Wykonano pomiary dozymetryczne określające geometrię oraz jakość stosowanej wiązki terapeutycznej osobno dla każdego aparatu terapeutycznego. Określono wartości spadku procentowych dawek zależnych od głębokości w napromienianym środowisku PDD {ang. Pcrcentage Dose Dcpth 1 - PDD), wydajność aparatu terapeutycznego oraz profil wiązki promieniowania. Zmierzone parametry pozwoliły na określenie rozkładu dawki dla poszczególnych punktów leżących wzdłuż osi ciała pacjenta, w osi prostopadłej do osi centralnej wiązki promieniowania. W celu zapewnienia powtarzalności ułożenia chorego w kolejnych frakcjach napromieniania powstał projekt ramy terapeutycznej oraz mobilnego stołu przeznaczonego dla opracowanej techniki napromieniania TBI, a następnie wykonano urządzenie według tego projektu w przygotowywaniu którego brałam czynny udział. Niedobory tkanki w płaszczyźnie prostopadłej do padania wiązki promieniowania lub zbyt niską jej gęstość uzupełnia się materiałami tkankopodobnymi. Zabezpieczają one pacjenta przed przekroczeniem dawki w linii środkowej jego ciała. W tym celu wyznaczony został współczynnik korekcji dawki w warstwie bolusa o znanej grubości. Jako dostępny i funkcjonalny materiał stanowiący bolus wybrano ziarna ryżu umieszczone w podwójnych bawełnianych woreczkach o wymiarach 10 cm x 15 cm. łatwych do zachowania higieny. Przyjęty wzorzec postępowania z pacjentem przygotowywanym do napromieniania jak i etapy jego realizacji stanowią: Etap I: - kwalifikacja do leczenia oraz symulacja wstępna, - wykonanie tomografii komputerowej TK (ang. CT - Computed Tomography). Etap II: - przygotowanie schematu napromieniania, - wykonanie pomiarów wydajności aparatu bezpośrednio przed napromienianiem pacjenta, - sprawdzenie poprawności planu napromieniania oraz wykonania osłon. Etap III: - realizacja napromieniania. Precyzyjny opis postępowania z pacjentem oraz przygotowania i realizacji TBI zawarto w V rozdziale tej pracy. W pracy poddano analizie wyniki pomiarów wartości dawek in vivo realizowanych przez zastosowanie detektorów typu MOSFET (ang. Metal-Oxide-Semiconductor-Field-Effect-Transistor) pod względem jednorodności rozkładu dawki w ciele pacjenta, ze szczególnym zwróceniem uwagi na rejon klatki piersiowej - aby chronić znajdujące się tam struktury krytyczne. Początkowo, do końca roku 2004 pomiary dawek in vivo wykonywano także przy użyciu komory jonizacyjnej typu Farmer 0.6 cm3 firmy PT W. Oceniano także dwie grupy pacjentów napromienionych dwoma różnymi sposobami. Zakres tolerancji dawki określono na podstawie danych literaturowych i wytycznych zawartych w Raporcie 50 i Raporcie 24 Międzynarodowej Komisji ds. Jednostek promieniowania i Pomiarów ICRU (ang. International Commission of Radiation Units and Measurements) [14,15] względem dawki przypisanej do zdefiniowanego punktu PC (Punkt Centrowania w ią zki). Według literatury zakres ten powinien znajdować się w przedziale ±10% dawki przypisanej do punktu centrowania wiązki PC, choć dopuszcza się przedział sięgający ±15 % dawki przypisanej do punktu PC. Od sierpnia 2000 roku do grudnia 2009 roku napromieniono grupę 158 pacjentów według schematu przyjętego do realizacji przy użyciu akceleratora PRIMUS firmy Siemens. Napromienianie było kompilacją pól bocznych (lateralnych) oraz pól naprzeciwległych.

Body fluid identification is a crucial step in forensic investigation, and investigators have used various techniques. With the discovery of cell-specific mRNA and miRNA markers as well as their stability in certain conditions, co-analysis of DNA and RNA from the same sample is possible and can bring multiple benefits. The workflow can be streamlined and the frequent lack of forensic sample will no longer be an obstacle. The need for a robust co-extraction method of DNA and total RNA is clear and there are several kits on the market to serve this need. This work aimed to establish an overview of nucleic acid extraction and dual extraction processes for body fluid identification as well as the use of commercial co-extraction kits.

The purpose of the present study was to compare total knee arthroplasty (TKA) rehabilitation with and without whole-body vibration (WBV) to 1) understand if WBV is a useful treatment during TKA rehabilitation to increase quadriceps strength and function, and 2) to investigate the effect of WBV on quadriceps voluntary muscle activation. Subject and Methods. Individuals post TKA (WBV n=8, control n=8) received physical therapy with and without WBV for four weeks. Quadriceps strength and muscle activation, function, perceived pain, and knee range of motion were measured. Results. No adverse side effects were reported in either group. There was a significant increase in strength and function for both groups (P<0.01). There was no difference pre to posttest between groups for strength, muscle activation, or pain (Hotelling’s T2=0.42, P=.80) or for function (F=0.54, P=0.66). Discussion and Conclusion. In individuals with TKA, WBV showed equal strength and function improvement to physical therapy directed progressive resistive exercise. Influence of WBV on muscle activation remains unclear, as initial muscle activation was near established normal quadriceps levels and remained so post treatment.

Introduction: Total Body Irradiation (TBI) is a radiotherapy treatment prescribed for patients with different form of leukaemia. It is part of conditioning regimen for hematopoietic stem cell transplantation and different techniques can be adopted to deliver TBI treatment. The conventional method consists of two static either lateral (LAT) or anterior-posterior/posterior-anterior (AP/PA) opposed photon beams, delivered with a linear accelerator (LINAC) at an extended source-surface distance, so as to cover the entire patient’s body with the fields. Developments on linear accelerator and multi-leaf collimator allowed to introduce Volumetric Modulated Arc Therapy (VMAT) for TBI treatments. Different centres tried to implement this technique addressing various treatment aspects (CT simulation, planning, pre-treatment dosimetry, patient positioning and immobilization systems) and they verified its effectiveness and advantages. This thesis is a dosimetric feasibility study, which purpose is to implement VMAT-based TBI in Grande Ospedale Metropolitano (GOM) Niguarda, where TBI treatment with conventional method is currently performed. Material & Methods: Feasibility of CT-simulation with Canon Aquilion Exceed LB CT, contouring and planning with MIM® 7.1.4 (MIM Software Inc.) and Monaco® 5.51.10 (Elekta AB, Sweden) Treatment Planning System (TPS), delivery with an Elekta LINAC equipped with Agility® (Elekta AB, Sweden) Multi Leaf Collimator (MLC) were investigated following different approaches found in literature. Dosimetric verifications of calculated and delivered doses were performed with Thermo Luminescent Dosimeters for point measurements and with the Delta4 phantom+ (ScandiDos AB, Sweden) for 3D measurements. The human-like Alderson Rando phantom was used for the entire implementation, while two whole-body retrospective CT acquisitions of two patients undergoing conventional TBI were used for planning optimization. Treatment goals of VMAT-TBI plan were to cover almost 95% of PTV volume with 95% of prescription dose (12 Gy delivered in 6 fractions twice a day) and to reduce mean dose to lungs below 10 Gy. Results: CT-simulation, contouring, planning and delivery of VMAT-TBI treatment were successfully performed. CT-simulation consisted of two CT-acquisitions with different orientations, one head-first supine (HFS) and the other feet-first supine (FFS). On the two CT-scans the PTV (the whole body reduced by 3 mm from the skin) and the OARs (lungs and, eventually, kidneys) were contoured, and subsequently, the planning was carried out on them. The VMAT-TBI treatment plan consisted of six overlapping fields with six different isocentres and maximum size of 40x40 cm2. Three fields were planned on the HFS-CT, while the other three on the FFS-CT, resulting in two plans optimized thanks to Monaco “Bias Dose” tool. Dosimetry, carried out simulating the treatment on Alderson Rando with TLDs and then with Delta4, verified that calculated dose by Monaco was comparable with delivered and measured dose. Average mean and maximum percentage differences between calculated and measured doses obtained from point measurements with TLDs were 2.3% and 10.4%. Gamma passing rate (3%/3 mm, global, 10% cut) of single beams dose distributions acquired with Delta4 resulted always higher than 99%, while dose distributions in junction regions between adjacent fields resulted higher than 90%. VMAT-TBI simulated treatment plans of two patients fulfilled treatment goals of PTV coverage and OARs sparing: average PTV volume that receive almost 95% of prescription dose resulted 97.44%, while average mean dose to lungs was 9.89 Gy and mean dose to kidneys was 10.11 Gy. Conclusions: This study confirms the feasibility of VMAT-based TBI in GOM Niguarda Hospital. Next step of the treatment implementation is to investigate more clinical oriented aspects, such as immobilization systems for patient’s positioning and setup verifications.

Evidence-based Canadian physical activity guidelines established specifically for pregnant women have shown to improve maternal and fetal outcomes, including prevention of adversities such as excess gestational weight gain, preeclampsia, and gestational diabetes. Unfortunately, most pregnant women fail to meet recommended guidelines for physical activity, and in many circumstances, the prevailing motive is due to a fear of overexertion and overheating harming the fetus. These concerns stem from reports of teratogenesis related to hyperthermia in several animal studies resulting in congenital fetal malformations. Although, due to disparities in thermoregulation between humans and animals, the findings are not entirely applicable to pregnant women. During exercise, the heat produced requires a given source of heat loss (i.e., skin blood flow/sweating) to maintain thermal homeostasis and a stable core temperature, preventing a continual rise in core temperature (i.e., teratogenesis). This thesis aims to separate the influence of pregnancy and body weight on oxygen consumption, heat production, heart rate, and rating of perceived exertion at rest (Study 1) and then during exercise (Study 2). On the other side of the heat balance equation is heat loss mechanisms; currently, the limited existing literature suggests that dry and evaporative heat loss increases as pregnancy progresses. Unfortunately, these findings are also based almost exclusively on animal studies. There has not been an established understanding of physiological, perceptual/behavioural responses in heat loss in pregnant women from early to late pregnancy, and the final study in this thesis sought to map the current literature in the format of a scoping review (Study 3). The findings of this thesis provide evidence that physiological measurements of oxygen consumption, heat production and heart rate are not influenced by stage of pregnancy, the responses increases/decrease according to total body mass. Additionally, both dry and evaporative heat loss responses appear to increase from early to late pregnancy.

Efficiency represents the ratio of work done to energy expended. In human movement, it is desirable to maximise the work done or minimise the energy expenditure. Whilst research has examined the efficiency of human movement for the lower and upper body, there is a paucity of research which considers the efficiency of a total body movement. Rowing is a movement which encompasses all parts of the body to generate locomotion and is a useful modality to measure total body efficiency. It was the aim of this research to develop a total body model of efficiency and explore how skill level of participants and assumptions of the modelling process affected the efficiency estimates Three studies were used to develop and evaluate the efficiency model. Firstly, the efficiency of ten healthy males was established using rowing, cycling and arm cranking. The model included internal work from motion capture and efficiency estimates were comparable to published literature, indicating the suitability of the model to estimate efficiency. Secondly, the model was developed to include a multi-segmented trunk and twelve novice and twelve skilled participants were assessed for efficiency. Whilst the efficiency estimates were similar to published results, novice participants were assessed as more efficient. Issues such as the unique physiology of trained rowers and a lack of energy transfers in the model were considered contributing factors. Finally the model was redeveloped to account for energy transfers, where skilled participants had higher efficiency at large workloads. This work presents a novel model for estimating efficiency during a rowing motion. The specific inclusion of energy transfers expands previous knowledge of internal work and efficiency, demonstrating a need to include energy transfers in the assessment of efficiency of a total body action.

The LeanScreenTM app uses photographs and touchscreen technology of an iPad or iPhone to estimate body composition using the Department of Defense (DoD) prediction equations that use cirumference measurements of the neck, abdomen, waist, and hips. The purpose of this study was to determine the validity and reliability of the LeanScreenTM app in 148 weight-stable adults (82 men, 66 women) who were normal weight, overweight, or obese as defined by body mass index. The percent body fat (%BF) of each subject was estimated during one visit using dual-energy x-ray absorptiometery (DXA) as the criterion measure, and three field methods: the LeanScreenTM app, manually measured circumferences, and an OMRON bioelectical impedance (BIA) device. The %BF of each subject was determined once using DXA. Each of two administrators assessed the %BF of each subject twice using the LeanScreenTM app, manually measured circumferences, and the OMRON BIA device. When using the LeanScreenTM app, administrators assessed body composition using photographs they had taken and the photographs taken by the other administrator. Validity was established by comparing estimates of %BF from the LeanScreenTM app, manually measured circumferences, and the OMRON BIA device to %BF values obtained from DXA. Inter- and intrarater reliability was determined using mutliple measurements taken by each of two administrators. The three field methods were compared to DXA using mixed model ANOVA and Bland-Altman analyses. Analysis of the data revealed that the LeanScreenTM app, manually measured circumferences, and the OMRON BIA device significantly underestimated (p < 0.05) the %BF determined by DXA by an average of -3.26 ± 3.57 %BF, -4.82 ± 3.45 %BF, and -8.45 ± 3.48 %BF, respectively. Limits of agreement (LOA) for the LeanScreenTM app (6.99 %BF), manually measured circumferences (6.76 %BF), and the OMRON BIA device (6.82 %BF) were large. Slopes of the line-of-best-fit through the data in the Bland-Altman plots indicate that bias of %BF estimates using the LeanScreenTM app (slope = 0.06; p = 0.008) and the OMRON BIA device (slope = 0.15; p < 0.0001) increased as %BF increased. For each method of assessment, minimal variance could be attributed to different administrators peforming the assessment and each administrator performing multiple assessments. All inter- and intrarater reliability coefficients of the LeanScreenTM app, manually measured circumferences, and OMRON BIA estimates of %BF exceeded 0.99. The results of this study indicate that all three field methods of body composition assessments were highly reliable, however, these field measures are not recommended for use in the assessments of %BF due to a significant bias and large limits of agreements.

Survivors of bone marrow transplant (BMT) with total body irradiation (TBI) in childhood are known to suffer late-effects due to toxicities of malignancy and its treatments including chemotherapy, glucocorticoids and TBI. Well described late-effects include short stature, gonadal failure, growth hormone deficiency (GHD), fatigue and reduced quality oflife (QOL). Emerging late-effects include increased central adiposity, reduced lean mass, increased risk of metabolic syndrome and cardiovascular mortality. Many features are shared with the GHD phenotype but the effects of growth hormone (GH) treatment are unknown. Aims of the research were as follows: - To describe the BMT/TBI phenotype in more detail in reference to body composition, insulin resistance, cytokines and cardiovascular risk markers. To investigate the GH axis in further detail using overnight growth hormone profiles, IGF-l generation tests, and the response to GH treatment over the first year. To examine the HP A axis using overnight cortisol profiles. To investigate the effects of an exercise intervention on body composition, insulin resistance, and cardiovascular risk. Results confirmed increased adiposity and reduced lean mass in BMT/TBI survivors with and without GHD and ameliorated by GH treatment. Increased risk of diabetes, metabolic syndrome and dyslipidaemia were demonstrated. Data showed a high prevalence of GHD in BMT/TBI survivors after adjustment for adiposity and that this persisted into adulthood and evolved with time since BMT/TBI. GH treatment resulted in improved height velocity and body composition but not improved metabolic and cardiovascular risk factors. There were no differences in response to GH treatment between BMT/TBI survivors and controls. The HPA axis studies showed novel changes in BMT/TBI survivors with clear gender differences in free cortisol index levels, including raised overnight levels in male survivors and blunted morning levels in female survivors. The exercise intervention showed improvements in fitness and insulin resistance but not body composition or cardiovascular risk markers. Further studies are required to investigate the mechanism of the development of diabetes and the metabolic syndrome in this group and further secondary prevention strategies are required to improve long-term cardiovascular outcomes

Philosophiae Doctor - PhD
Background: Obesity is increasing worldwide, and cultural perception of body image is considered an important contributor to the obesity epidemic among black Africans. Aim: To explore the association between body image perceptions and perceived obesity threat, change in adiposity, and total cardiovascular disease (CVD) mortality risk. Study Design: This is a mixed-methods study embedded in the PURE longitudinal cohort study involving adults aged 35-78 years in South Africa. Data Collection/Analysis: This included analysis of baseline cross-sectional data, the conduct of a qualitative study and a cross-sectional follow-up survey. Sex-specific logistic regression models of excessive adiposity were determined. Body image perception indexes were obtained based on 'Feel- Ideal' difference (FID) and 'Feel-Actual' discordance (FAD). Bivariate analyses and analysis of variance were used to determine the relationships between body image and adiposity, annual changes in weight and adiposity. The correlations between body image indexes (FID and FAD) and total 10- year CVD risk score were determined – controlling for possible confounders. Qualitative data was managed with ATLAS-ti software and analysed thematically. Results: The prevalence of excessive body fat at baseline and at 5-year follow-up based on body fat percent were 96.0% and 79.6% for women, and 44.3% and 62.2% for men respectively. The majority of the obese (85%) and overweight (79%) participants underestimated their weight, and weight discordance status was inversely associated with the willingness to lose weight. Mean total 10-year CVD risk score was 18.7%, and 61% of men and 26% of women with body mass index (BMI) ≥ 25 kg/m2 had CVD risk scores ≥ 20%. Bivariate analyses indicated that FID and FAD were significantly associated with annual changes in weight and adiposity. FAD index had a significant but weak correlation with total CVD risk score (r = 0.13, p-value = 0.001) when adjusted for covariates. Conclusion: Body image discordance was associated with an annual change in adiposity, total 10- year CVD risk scores, and there was poor obesity risk perception, and low motivation towards weight loss among predominantly obese black adults with negative body image. Interventions to reduce obesity need to address negative body image, poor obesity risk perception, self-efficacy and motivation towards weight loss.
National Research Foundation; Chromnic Disease Initiative for Africa (CDIA); National Institute of Health (NIH)

Hip osteoarthritis (OA) is a progressive joint disorder that causes pain and motor dysfunction, which imposes a substantial health burden on the individual and health care system. The clinical end-point for severe hip OA is a total hip replacement. However hip replacement is an invasive and costly medical procedure, so efforts to prolong time to joint replacement through interventions that reduce pain and maximise function are required. A necessary requirement for developing efficacious interventions to manage hip OA is a thorough understanding of the musculoskeletal alterations associated with the disease so that they can be more directly targeted. Research to date has predominantly focused on characterising these deficits in advanced stages of the disease. These prior studies suggest that muscle weakness, altered femoral geometry and increased BMI, total body fat and intramuscular fat content are features of advanced hip OA, which together have the potential to alter the mechanical and metabolic environment of the hip joint. A need therefore existed to better understand the musculoskeletal deficits associated with earlier stages of hip OA, and how they change over time. The general aim of this thesis was therefore to investigate muscle, bone and fat characteristics in individuals with mild-to-moderate hip OA and age-matched controls at baseline and at 12-months follow-up.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Allied Health
Griffith Health
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The project investigates the dietary factors that influence a person’s hydration status, primarily by measuring body water turnover. Body water turnover is commonly reported as a marker of hydration status for its measurement of total fluid gains and losses over a 24-hour period and can be particularly useful in predicting (and hence managing) fluid loss in individuals experiencing large losses. The study found that active individuals have faster water turnovers, explained by the larger water volumes they consume but also their overall fibre intake. This research has important implications for the impact of dehydration on physical and/or cognitive declines.

Context: One to three years after Roux-en-Y gastric bypass (RYGB) surgery, patients demonstrate progressive loss of bone mineral density (BMD) and accelerated bone turnover, especially at weight-bearing sites. Objective: The objective was to measure BMD and bone metabolism in relation to extent of weight lost long-term after RYGB. Design and Setting: This retrospective study was conducted ten years after RYGB in a university laboratory and bone metabolism unit. Patients: Fifty subjects (38 females, 12 males) aged 33-69y were recruited from a university bariatric surgery clinic an average of 10.17±3.45y after RYGB. Main Outcome Measure: The primary outcome measurement was the association of total body weight loss with BMD and serum markers of bone turnover. Results: Patients lost 46.0±20.0 kg ten years post-operatively (p<.01). Percentage total body weight loss (%TBWL) was negatively correlated with BMD (total body: r=-.40, lumbar 1-4: r=-.36, and total hip: r=-.51, all p's<.01) and were positively correlated with serum levels of osteocalcin (r=.40, p<.05). When patients were collapsed into tertiles of %TBWL, weight loss >30% was associated with poorest bone health as indicated by lowest BMD scores at all sites (p<.05) and highest levels of osteocalcin (p<.005). Conclusions: The magnitude of total body weight loss long-term after RYGB may provide insight to patient skeletal health ten years post-surgery. Patients who lost >30% total body weight had low BMD and high levels of bone remodeling at the ten-year mark. Healthcare professionals should be aware the risk of fracture or osteoporosis may be elevated among those who lose >30% total body weight ten years after RYGB.
Contexte: Les patients qui ont subi une chirurgie bariatrique de type Roux- en-Y démontrent, un à trois ans après la chirurgie, une perte progressive de leur densité minérale osseuse ainsi qu'un remodelage accéléré de leurs os, surtout dans les régions où le poids est supporté. Objectif: L'objectif fut de mesurer la densité minérale et le métabolisme des os, en relation avec la perte de poids à long terme après une chirurgie bariatrique de type Roux-en-Y.Désign: Cette étude rétrospective a été conçue dix ans après la chirurgie bariatrique de type Roux-en-Y, dans un environnent de laboratoire universitaire et une unité de métabolisme osseuse. Patients: Cinquante patients (38 femmes, 12 hommes), âgés de 33 à 69 ans, ont été recrutés par une clinique de chirurgie bariatrique universitaire environ 10.17±3.45 ans après avoir subi leur chirurgie bariatrique de type Roux-en-Y.Mesure principale: Le résultat des mesures d'intérêts primaires fut l'association entre la perte de poids totale et la perte de densité minérale osseuse ainsi que les marqueurs de sérum pour le remodelage osseux.Résultats: Les patients ont perdu en moyenne 46.0±20.0 kg au cours des dix années suivants la chirurgie (p<.01). Le pourcentage total de poids perdu (%TBWL) était négativement corrélé avec la densité osseuse (corps complet: r=-.40, lombaires 1-4: r=-.36, et hanches: r=-.51, tous p<.01) et positivement corrélé avec le niveau de sérum d'ostéocalcine (r=.40, p<.05). Quand les patients furent séparés en tiers de %TBWL, la perte de poids >30% était associée avec les pires indices de santé osseuse, dont les moins hauts rangs de densité minérale osseuse dans tous les sites et les niveaux les plus élevés d'ostéocalcine.Conclusions: L'ampleur de la perte de poids totale à long terme après une chirurgie bariatrique de type Roux-en-Y peut fournir des indices par rapport à la santé squelettique, dix ans après la chirurgie. Les patients qui ont perdu >30% de leur poids total initial avaient la plus basse densité minérale osseuse et le plus haut niveau de remodelage osseux, dix ans suivant la chirurgie. Les professionnels de la santé devraient être avertis des risques de fractures ou d'ostéoporose élevés, parmi les patients qui ont une perte de poids totale >30%, dix ans après une chirurgie bariatrique de type Roux-en-Y.

O presente estudo investigou o efeito de diferentes intensidades do treinamento de força (TF), aplicadas com volume total de treino (VTT) equalizado, nos ganhos de força dinâmica máxima (1RM) e massa muscular dos membros superiores e inferiores. Trinta voluntários do sexo masculino, com idade entre 18 e 30 anos, participaram de 12 semanas de TF com uma frequência semanal de duas sessões. Foi utilizado um protocolo de treinamento unilateral com um dos lados do corpo realizando o exercício com intensidade equivalente a 20% 1RM (G20) e o lado contralateral utilizando uma das três intensidades 40%, 60% ou 80% 1RM (G40, G60 e G80, respectivamente). O grupo G20 realizava três séries compostas de repetições até a falha concêntrica e o VTT era calculado e replicado para os demais grupos. A força dinâmica máxima e a área de secção transversa (AST) dos músculos flexores do cotovelo e do vasto lateral foram avaliadas nos momentos pré, 6 semanas e pós-treinamento. Os resultados demonstraram que os grupos G40, G60 e G80 apresentaram ganhos similares de AST (25%, 25,1% e 25%, flexores do cotovelo e 20,5%, 20,4% e 19,5% vasto lateral, respectivamente, p<0,05). Somente o grupo G80 demonstrou diferença significante com o grupo G20 na comparação do período pós-treinamento (25% e 14,4%, respectivamente para os flexores do cotovelo e 19,5% e 7,9%, respectivamente para vasto lateral, p<0,05). Para os ganhos de 1RM o grupo G80 demonstrou maiores aumentos após 12 semanas de TF para a flexão unilateral do cotovelo na posição em pé (54,2% p<0,05) e para o leg press 45º os grupos G60 e G80 demonstraram os maiores aumentos (55,4% e 45,7%, respectivamente, p<0,05). Assim, quando o VTT foi equalizado entre diferentes intensidades (40, 60 e 80% 1RM) os ganhos da AST tanto dos flexores do cotovelo quanto o vasto lateral foram semelhantes e a intensidade de 20% 1RM não causou aumento significante da AST. No que diz respeito a força muscular as intensidades mais elevadas (60% e 80% 1RM) foram superiores em promover ganhos de força do que as demais intensidades utilizadas. Esses dados sugerem que ao equalizar o VTT os ganhos de massa muscular são semelhantes para as intensidades de treinamento entre 40- 80% 1RM. Além disso, a intensidade de 20% 1RM, mesmo com o VTT equalizado com as intensidades maiores, não promove aumentos de massa muscular para ambos os segmentos corporais. Por outro lado, intensidades altas de treinamento produzem os maiores ganhos de força máxima em membros superiores e inferiores
The present study investigated the effect of different resistance training (RT) intensities, with equal total training volume (TTV), on maximal dynamic strength (1RM) and upper and lower limbs muscle cross sectional area (CSA). Thirty men engaged in a twice a week training period for 12 weeks. The study was carried out with a within subject design. Thus, one leg and one arm were set at 20% 1RM (G20) for all subjects and the contralateral side was randomly assigned to one of three possible groups (i.e. G40, G60 and G80, 40%, 60% and 80% 1RM, respectively). The leg and arm that were set at 20% 1RM always started the resistance training session and performed 3 sets to concentric muscle failure. TTV (sets x repetition x mass) was recorded and replicated to other groups. The maximal dynamic strength and elbow flexors and vastus lateralis CSA were assessed at pre, 6 weeks and post intervention. The main results showed similar increases in CSA for G40, G60 and G80 groups (25%, 25,1% and 25%, elbow flexors and 20,5%, 20,4% and 19,5% vastus lateralis, respectively, p<0,05). Only the G80 group showed significant difference from G20 group after 12 weeks of resistance training (25% and 14,4%, respectively for elbow flexors and 19,5% and 7,9%, respectively for vastus lateralis, p<0,05). Regarding 1RM the G80 group showed the greatest increase post 12 weeks of resistance training for elbow flexion (54.2% p<0,05) and for leg press 45º the groups G60 and G80 showed the greatest increases (55.4% e 45.7%, respectively, p<0,05). In summary, when different RT intensities (40, 60 and 80% 1RM) performed the same TTV gains of CSA for elbow flexors and vastus lateralis muscles are similar between them and intensities of 20% 1RM did not result a significant increase in CSA. For muscle strength the highest intensities (60% and 80% 1RM) seemed to be superior to promote strength gains than other intensities. These findings indicate that intensities between 40-80% 1RM with equal TTV can elicit significant increase in muscle hypertrophy in upper and lower limbs; however, high intensities are superior to augment strength adaptations in upper and lower limbs

Total body electrical conductivity (TOBEC) is a noninvasive method for the estimation of lean mass in live subjects. Lipid content can be calculated from the body mass measured and the lean mass estimated from TOBEC. I used live American Kestrels (Falco sparverius) to study the accuracy of this method. TOBEC measurements were compared to actual body content determined by Soxhlet fat extraction using petroleum ether as the solvent. TOBEC estimated 73.7% of the variation in lean mass in a sample of 21 kestrels. The use of restraining devices (Vetrap and cardboard cylinders) altered the TOBEC measurement but only by an average of 1.92% and 0.83%, respectively. TOBEC estimated 83.8% of the variation in lean mass for 21 kestrel carcasses warmed to 39.8oC. No significant difference was found between the slope or elevation of the calibration lines developed using live or dead kestrels. A significant difference was found between measurements taken at two different positions. Body temperature altered the TOBEC measurements by an average of 1.54% (SE = 0.55) for each 10C change over a temperature range of 7.00C (37.3-44.4). The calibration line developed for kestrels was used to estimate lean mass and compute fat mass of migrating kestrels, Sharp-shinned Hawks (Accipiter striatus) and Merlins (Fa/co co/umbarius). The average percent fat mass of kestrels trapped during migration at Cape May, New Jersey, was 6.01 % (SE = 1.92, n = 1 2) for males and 8.51 % (SE = 2.00, n = 13) for females. The difference in lean mass between male and female, and between early, mid-season, and late migrating Sharp-shinned Hawks differed significantly during migration. The fat mass of Sharp-shinned Hawks averaged 5.55% (SE = 0.94, n = 53) for males and 10.92% (SE = 0.80, n = 87) for females. Male Merlins had an average fat mass of 18.05% (SE = 3.35, n = 7) and females averaged 14.19% (SE = 3.15, n = 8).

Static stretching has often been found to decrease performance in power and speed activities, but dynamic warm-ups usually increase performance. We examined the effects of a mini-band warm-up, a medicine ball warm-up, and static stretching on 10m and 20m sprint times, as well as overhead medicine ball throw performance. A convenience sample of 24 Division I women?s soccer players participated, however 5 subjects dropped out due to sustaining injuries from a weekend soccer tournament. The subjects completed the three warm-ups and a control 5 minute jog condition on separate days and were tested on the 10m and 20m sprint times and overhead medicine ball throw. ANOVA?s and follow-up paired t-tests (p<0.05) were used to determine differences between the warm-ups. Significant differences were found between groups for the 10m sprint times but not for the 20m sprint times or the overhead medicine ball throw.

GM1 gangliosidosis is an autosomal recessive lysosomal storage disease, caused by a deficiency in the enzyme β-galactosidase. The disease affects the CNS, liver, kidney, heart and skeletal system, leading to severe neurodegeneration and death. We propose to treat this disorder using ex vivo hematopoietic stem cell therapy. The effectiveness of this therapy requires the recruitment of transduced donor cells to the CNS. This is only found to occur after mice are conditioned with total body irradiation, due to the increase in CNS cytokine production and blood brain barrier permeability that occurs. As the use of total body irradiation in pediatric patients has been linked to future developmental problems, this myeloablation approach is often avoided in younger patients in favor of a conditioning regimen using the chemotherapy drugs, busulfan and cyclophosphamide. Whether donor cells can enter the CNS when a busulfan and cyclophosphamide conditioning regimen is used has not been determined. In this study we plan to quantify the cytokine and blood-brain barrier permeability increases necessary for donor cells to be recruited to the CNS after total body irradiation. We will then investigate whether busulfan and cyclophosphamide conditioning and/or the chronic neuroinflammation present in GM1 mice can produce similar conditions and facilitate the recruitment of donor hematopoietic stem cells to the CNS. Finally we will assess whether ex vivo hematopoietic stem cell gene therapy is still an effective therapy when busulfan and cyclophosphamide are used for myeloablative conditioning.

Als Resultat überhöhter Energieaufnahme und zu geringen Energieverbrauchs beobachten wir eine über das normale Maß hinausgehende Akkumulation von Fettgewebe, die sich als Adipositas manifestiert. Sie gilt als einer der Hauptrisikofaktoren für Krankheiten des metabolischen Syndroms. Im Rahmen von Prävention, Diagnose und Therapie der Adipositas, muss ihr wesentliches Charakteristikum; der individuelle Körperfettanteil; einer Messung zugänglich gemacht werden. Eine direkte Bestimmung der Körperzusammensetzung erlauben die Neutronenaktivierungsanalyse und die chemische Analyse. Beide Verfahren sind sehr genau, aber aufwendig und kostenintensiv und darüber hinaus die chemische Analyse nur am menschlichen Cadaver praktizierbar. Um dennoch die Körperzusammensetzung hinreichend genau bestimmen zu können, wurden zahlreiche indirekte Messverfahren entwickelt. Man kann sie in Labor- und Feldmethoden untergliedern. Die Labormethoden bestechen durch hohe Genauigkeit und Reproduzierbarkeit, sind aber zumeist aufwendig und teuer. Feldmethoden sind im Gegensatz dazu leicht anwendbar, transportabel und preiswert, weisen aber eine weniger hohe Genauigkeit und Reproduzierbarkeit auf.

In der vorgestellten Arbeit wird über eine jüngere Entwicklung, die das Prinzip der unterschiedlichen Leitfähigkeit für den elektrischen Strom durch die verschiedenen Gewebe des Körpers nutzt, berichtet. Der Prototyp eines Gerätes wurde innerhalb eines von der EU geförderten multizentrischen Projekts entwickelt und auf seine Einsatzfähigkeit und Qualität hin geprüft. Der Schwerpunkt der Arbeit liegt auf der Einschätzung der Körperzusammensetzung normal- und übergewichtiger Probanden mit der neu entwickelten Technik. Das vorliegende Studiendesign diente nicht nur der Beurteilung der neuen Technik die Körperzusammensetzung und Veränderungen dieser zu erfassen, sondern darüber hinaus, etablierte Methoden hinsichtlich ihrer Genauigkeit zu bewerten. Bezüglich ihrer Anwendbarkeit und Reproduzierbarkeit hat die neue Methode Hoffnung geweckt, sich als eine Feldmethode zu etablieren. Auf der anderen Seite zeigte sich in Abhängigkeit der Gesamtkörperfettmasse eine Überschätzung der Zielgröße im Vergleich zur Referenzmethode (dual energy x ray absorptiometry (DXA)). Die Abweichungen waren dabei gerade für das einzelne Individuum sehr groß. Technische Verbesserungen und die Entwicklung spezifischer Regressionsgleichungen könnten in Zukunft zu einer wesentlichen Verbesserung der neuen Methode beitragen.

Die Labormethode "Air Displacement Plethysmography" konnte durch die guten Übereinstimmungen der Ergebnisse mit denen der Referenzmethode DXA und die einfache Anwendung überzeugen. Sie stellt eine durchaus konkurrenzfähige Alternative zur Hydrodensitometrie dar, die noch heute als "goldener Standard" zur Erfassung der Körperzusammensetzung akzeptiert wird. Im Verlauf der durchgeführten Studie stellte sich heraus, dass die Hydrodensitometrie sehr hohe Anforderungen an den Probanden stellt. Das Untertauchen des gesamten Körpers unter Wasser in Kombination mit einer maximalen Ausatmung erwies sich als sehr problematisch. Die dabei auftretenden Fehler schlugen sich in der Berechnung der Gesamtkörperfettmasse des einzelnen Individuums wieder und führten zu zum Teil erheblichen Abweichungen der Ergebnisse von denen der Referenzmethode.

Die Feldmethoden bioelektrische Impedanzanalyse und Hautfaltendickenmessung erwiesen sich als kostengünstige und leicht anwendbare Methoden. Die Ergebnisse beider Methoden stimmten im Mittel gut mit den Ergebnissen der Referenzmethoden überein. Dennoch zeigte die BIA größere Abstriche in der Beurteilung der Gesamtkörperfettmasse des einzelnen Individuums und bei der Dokumentation von Veränderungen der Gesamtkörperfettmasse. Die Hautfaltendickenmessung stellt – wendet man sie korrekt an – eine Methode dar, die sowohl die Gesamtkörperfettmasse als auch Veränderungen dieser gut erfassen kann. In Abhängigkeit der geforderten Genauigkeit kann diese Methode für die Erfassung der Körperzusammensetzung empfohlen werden.

Demnach bleibt die Frage unbeantwortet, inwieweit die indirekten Methoden in der Lage sind, die "wahre" Körperzusammensetzung adäquat zu erfassen. Jede neu entwickelte Methode – die möglichst viele Vorteile in sich vereint – wird wieder vor dem Problem stehen: eine geeignete und dabei praktikable Referenzmethode zu finden, die die wahre Körperzusammensetzung zu bestimmen in der Lage ist. Daher sollte neben dem Streben nach der Entwicklung einer Methode, die genau und leicht anwendbar ist, das Hauptaugenmerk auf die Überarbeitung der zugrunde liegenden Modellvorstellungen und die Verbesserung von Regressionsgleichungen gelegt werden.
Western industrial countries are characterized by sedentary lifestyle and a high-fat and simple carbohydrate diet. Decrease physical activity and increase energy intake are leading to an epidemic increase of overweight and obesity. Obesity is defined as the presence of excess adipose tissue and has been associated with an increased risk for diseases of the metabolic syndrome. Thus, the importance of obtaining reliable and accurate body fat estimates is essential not only for the prevention, but also for the diagnosis and therapy of obesity. Direct chemical analysis is the most definitive method for determining human body composition. The few data obtained on the composition of adult bodies stemmed from cadaver analyses, dated back to 1945 and 1956. These results contributed greatly to the actual fundamental knowledge about human body composition. Obviously, the method is limited by the precondition of needing the human cadaver and the high complexity of the analyses. Because of this limitation, indirect methods have been developed during the last decades. To date more than ten methods to estimate body composition in vivo are available. The methods can be generally organized into two groups: laboratory and fields methods. Laboratory methods have high accuracy and reproducibility, but are complex and very expensive, whereas field methods are easy to use and economically priced, but less accurate. A new device that combines the positive features of both, laboratory and field methods is needed . An already existing method - Total Body Electrical Conductivity (TOBEC) - meets the requirements for such new device. The technique is based on the principle, that lean tissue is far more electrically conductive than fat, due to the higher content of electrolytes in the fat-free mass. The difference between impedance when a subject is inside and outside of the generated field is an index of the total electrical conductivity of the body, which, in turn is proportional to the lean body mass of the subject.

Within the European Project BodyLife (IST - 2000 - 25410) a new field method for estimation the human body composition was developed. To assess the suitability of the new technique the present study aimed to evaluate the reliability of nTOBEC and to validate it against established laboratory and field methods.

Within the project the development of the new method (nTOBEC) succeeded to combine the TOBEC-principle, and additionally, to be transportable and easy to use.

The high reliability coefficients found in this investigation indicate that nTOBEC is an extremely reliable instrument. By application the new technique we observed a significant overestimation of total body fat mass compared the reference method dual energy x ray absorptiometry (DXA) in both, males and females. However, nTOBEC could document changes in total body fat mass during a weight loss intervention trial.
Our data suggest nTOBEC deserves further investigation with the intention of establishing nTOBEC as a non-invasive method for accurately quantifying total body fat mass.
Aside from these results we observed accurate results for the easy to use laboratory method "air displacement plethysmography" compared to the results measured by DXA. Furthermore, the field methods - bioelectrical impedance analysis and skinfold thickness measurement – produced good results compared to the reference method.

This is work concerned with modification, assessment, optimisation, and calibration of a prompt-capture neutron activation analysis facility based on a ²⁵²Cf source for the measurement of total body nitrogen in vivo via the ¹⁴N(n,γ)¹⁵N reaction. To achieve these goals, the Swansea facility was studied by both theoretical simulation and experimental measurement. The geometry of the facility was entered into a radiation transport modelling MCNP code based on a Monte Carlo process. A number of configurations were tested to pursue fulfilment of the above goals. Regarding the neutron beam, the results of calculations performed with MCNP code together with experimental measurements of thermal flux indicated that the facility can deliver a suitable thermal flux throughout a phantom when irradiated using a 5 cm bismuth collimator (the 'short' collimator) and 50 μg ²⁵²Cf source. Use of a lower activity neutron source to that originally utilized with this facility (200 μg) permits a considerable cost saving. For the 'short' collimator, gamma-ray detector positions were investigated theoretically and were complemented by practical measurements; optimum positions at which the maximum values of signal-to-noise ratio in the nitrogen and hydrogen region of interest and the uniformity of irradiation and detection of nitrogen were determined. The MCNP simulations have shown that the contribution of the hydrogen counts (background) arising from the facility can be a considerable proportion (up to 19%) of the calibration phantom counts and can have a significant effect on the calculation of total body nitrogen. A correction for the hydrogen background contribution has been implemented. MCNP calculations were also used to assess the influence on calibration of overlying fat around a body phantom. The results indicate that errors of typically 35% for a 6 cm fat layer may arise if calibration is undertaken using a homogenous tissue equivalent solution phantom but where in practices the subject of the same external dimensions has a layer of fat.

Adolescência é o período de transição entre a infância e a vida adulta, caracterizado pelos impulsos do desenvolvimento físico, mental, emocional, sexual e social. Essa faixa etária, ao longo dos anos tem apresentado aumento da prevalência de sobrepeso e obesidade e danos e agravos à saúde provocados pelas comorbidades associadas. Os fatores que contribuem para esse processo são a alimentação e a inatividade física, portanto conhecer e saber escolher o melhor método para avaliar gasto energético basal e total, atividade física e a composição corporal dessa população ajuda os profissionais da saúde a trilharem soluções mais promissoras para o combate da obesidade e a formação de adultos mais saudáveis. O objetivo principal do presente estudo foi avaliar Gasto Energético e fatores diretamente relacionados como Consumo Alimentar e Padrão de Atividade Física em Adolescentes Obesos e Eutróficos. Foram estudados 86 adolescentes obesos e eutróficos de idade de 11 a 14 anos de ambos os sexos de escolas públicas e particulares de Ribeirão Preto. Foi avaliada a atividade física por meio do acelerômetro tri-axial, a composição corporal por absorcimetria de raio X de dupla energia, bioimpedância elétrica e óxido de deutério e gasto energético basal por calorimetria indireta e gasto energético total por água duplamente marcada. Os dados foram analisados pelo teste de normalidade Kolmogorov Smirnov, teste Anova com pós teste de Tukey e comparações por método Bland-Altman. O peso muscular pelo DXA de adolescentes obesos foi maior do que em adolescentes eutróficos. Houve diferença estatística entre obesos e eutróficos nas variáveis MMkg, MM%, MGkg e MG%. Analisando a composição corporal por BIA e OD podemos ver que a BIA superestima os resultados. Quanto ao gasto energético, não houve diferença estatística entre os grupo em relação ao GEB e GET, para o GET ser maior independe da atividade física em número de passos no dia, pois o GEB em X obesos (meninos e meninas) é maior quando comparado com eutróficos. O nível de atividade física dos adolescentes se mostrou semelhante entre os obesos e eutróficos, apesar dos obesos darem muito menos passos ao longo do dia. Em nosso estudo todas as variáveis foram diferentes entre os grupos. Foi constatado que os adolescentes obesos apresentam maior GEB por terem maior massa muscular, o que já eleva o GET, apesar de apresentarem AF menos intensa que os eutróficos, confirmando nossa hipótese inicial.
Adolescence is the transitional period between childhood and adulthood, characterized by the impulses of the physical, mental, emotional, sexual and social development. This age group, all over the years, has shown increasing prevalence of overweight and obesity, damage and health problems caused by associated comorbidities. Factors that contribute to this process are the diet and physical inactivity, so knowing how to choose the best method to assess basal and total energy expenditure, physical activity and body composition of this population helps health professionals to find the best solutions to deal with obesity and how to guide their patients on how to become healthier adults. The main objective of this study was to evaluate Energy Expenditure and directly related factors such as Food Consumption and Physical Activity in Adolescents Obese and Eutrophic. We studied 86 adolescents aged between 11 and 14 years of both genders, obese and non-obese, from public and private schools in Ribeirão Preto. Physical Activity was evaluate by tri-axial accelerometer, body composition by dual-energy X-ray absorptiometry, electric bioimpedance and deuterium oxide, and basal energy expenditure was evaluate by indirect calorimetry and total energy expenditure by doubly labeled water. Data was analysed by Kolmogorov Smirnov to check normality, Anova with post test Tukey and comparisons by Bland-Altman method. The muscle weight by DXA of obese adolescents was higher than in normal weight adolescents. There was statistical difference between obese and normal weight in MMkg variables, MM % BFkg and BF %. Analyzing body composition by BIA and OD we can see that the BIA overestimates the results. In relation to the energy expenditure, there was no statistical difference between the groups in relation to the REE and TEE to the TEE be most independent of physical activity in number of steps in the day, because the REE in obese (boys and girls) is higher as compared with eutrophic. XII The level of physical activity in adolescents was similar between the obese ones and normal weight ones, while obese ones had much less steps throughout the day. In our study all the variables were different between the grupos. We found that obese adolescents have higher REE because they have more muscle mass, which already raises the TEE, despite having less intense physical activity that eutrophic adolescents, confirming our initial hypothesis.

The prevalence of obesity continues to increase despite considerable research and innovation regarding treatment and management strategies. When completed as prescribed, exercise training is associated with numerous health benefits and predictable levels of weight loss. However, under free-living conditions the benefits of exercise are less consistent, suggesting that non-adherence and/or a compensatory response in non-exercise activity thermogenesis (NEAT) may be occurring. The accurate quantification of all components of total energy expenditure (TEE), including TEE itself, was imperative to elucidate the primary research question relating to the impact of exercise on TEE. In addition, the measurement of changes in body composition and the response to prescribed exercise were assessed in methodological and pilot investigations. Following this extensive background, the primary research question relating to the effect of exercise on levels of TEE and the associated implications of such a compensatory response could be more rigorously investigated. The first study investigated the variability in isotopic equilibrium time under field conditions, and the impact of this variability on estimates of total body water (TBW) and body composition when using the deuterium dilution technique. Following the collection of a fasting baseline urine sample, 10 women and 10 men were dosed with deuterium oxide (0.05g/kg body weight). Urine samples were collected every hour for 8 hours. The samples were analysed using isotope ratio mass spectrometry and time to equilibration was determined using three commonly employed data analysis approaches. Isotopic equilibrium was reached by 50, 80 and 100% of participants at 4, 6 and 8 h, respectively. The mean group equilibration times determined using the three different plateau determination methods were 4.8 ± 1.5, 3.8 ± 0.8, and 4.9 ±1.4 h, respectively. Isotopic enrichment, TBW, and percent body fat estimates differed between early sampling times (3-5 h), but not later sampling times (5-8 h). Therefore, sampling < 6 hours post dose compared to sampling ≥ 6 hours resulted in greater relative measurement error in TBW and body composition estimates. Although differences in equilibration time were apparent between the three plateau determination approaches, sampling at 6 hours or later may decrease the likelihood of error in body composition estimates resultant from incomplete isotopic equilibration in a small proportion of individuals. In the second study, the aim was to measure the self-paced walking (SPW) speed of adults ranging in body size from normal to obese. The utility of heart rate monitors to estimate the energy cost of walking was also investigated. Twenty-nine participants (12 normal-weight, 17 overweight or obese) completed two outdoor walking tests to determine their SPW speed. A walking treadmill test with stages below, at, and above the SPW speed was completed to compare the energy expenditure estimates of the Polar S610 and WM42 heart rate monitors with that from indirect calorimetry. The average SPW speed was 1.7 ± 0.1 m*sec-1, which was equivalent to an exercise intensity of 48.6 ± 9.4 %VO2max (61.0 ± 7.1 %HRmax). There was no difference in the energy expenditure estimation between indirect calorimetry (4.7 ± 0.7 kcal*kg*-1*h-1), the S610 (4.8 ± 1.3 kcal*kg*-1*h-1) and the WM42 (4.8 ± 1.6 kcal*kg*-1*h-1). It was concluded that the heart rate monitors provided reasonable energy expenditure estimates at the group level. However considerable error was evident at the individual level, explained in part by exercise heart rate and fitness level, suggesting that an individualised calibration should be performed where possible. An additional finding from this study was that 145 to 215 minutes of SPW per week, dependent upon the level of adiposity, is required to meet the current American College of Sports Medicine (ACSM) guidelines for health of 1000 kcal*wk-1. The purpose of the third study was to establish the level of adherence to a specific exercise prescription (1500 kcal*wk-1) by objectively quantifying unsupervised exercise energy expenditure (ExEE) in a group of obese women. The 16-wk lifestyle intervention consisted of weekly meetings with research staff, combined with promotion of increased ExEE (1500 kcal*wk-1) and a decreased dietary intake (-500 kcal*d-1). Twenty-nine obese females (Body Mass Index = 36.8 ± 5.0 kg*m2, Body Fat = 49.6 ± 3.7 %) from a hospital-based lifestyle intervention were included in the analysis. ExEE was estimated and monitored weekly using heart rate monitoring. Body composition was measured before and after the intervention by dual-energy x-ray absorptiometry (DXA). Results indicated free-living adherence to the exercise prescription was modest and variable, with 14% of participants achieving the 1500 kcal*wk-1. The average weekly ExEE (768 kcal*wk-1) represented 51.2% of the total amount prescribed. ExEE was correlated with changes in body weight (r = 0.65, p < 0.001) and fat mass (r = 0.65, p = 0.0002). Achievement of a 5% weight loss target was dependent on an ExEE level of 1000 kcal*wk-1 (p <0.001). Exercise 'adherers' (> 000 kcal*wk-1) lost more weight (-9.9 vs. -4.1 kg), more fat mass (-6.8 vs. -3.0 kg), and more waist circumference (-9.8 vs. -5.6 cm) when compared to 'non-adherers' (< 1000 kcal*wk-1). The results suggest that the extent of supervision and monitoring influenced exercise adherence rates. The variability in adherence highlights the importance of objective monitoring of ExEE. Identification of individuals not complying with program targets may enable intervention staff to provide additional support or make individualised adjustments to the exercise prescription. The fourth study investigated issues relating to the management and interpretation of accelerometry data when the device is to be used to monitor levels of daily physical activity. Given the high between-individual variability in accelerometry output for a given walking speed, the use of a more individualised approach to the data management has been suggested. In addition, accelerometry was used to compare daily physical activity patterns between a supervised and unsupervised exercise prescription of the same dose (1500 kcal*wk-1) in overweight and obese women. Total energy expenditure, activity energy expenditure, and vector magnitude increased significantly during the intervention. Time spent in very low intensity movement decreased from baseline to the intervention (p < 0.01) in both the supervised (-18.6 min*d-1) and unsupervised (-68.5 min*d-1) group, whereas time spent in high and vigorous intensity movement increased significantly from baseline to the intervention (p < 0.05 and p < 0.0001, respectively). The increase in vigorous movement was significantly greater in the supervised group when compared to the unsupervised group (+11.5 vs. +5.4 min*d-1, p < 0.05). Time spent above three different moderate-intensity walking thresholds increased from baseline to the intervention (p < 0.0001). The threshold determination approach significantly affected the resultant outcomes (p < 0.0001) such that the standard threshold was significantly different to both group-specific and individualised approaches. Significant differences were also noted in accelerometer output between treadmill and overground walking (p < 0.0001). A positive finding of this study was that two different interventions aimed at increasing physical activity levels in a group of sedentary and obese women were successful in gaining modest increases in overall daily movement. The change observed appears to be a replacement of sedentary movement with more vigorous physical activity. Collectively, the differences observed between threshold determination approaches, as well as between treadmill and overground walking, highlight the need for standardised approaches to accelerometry data management and analysis. In addition, the findings suggest that obese women may benefit from a certain degree of exercise supervision to ensure compliance, however, strategies to encourage these women to continue with the exercise on their own without supervision are essential to making a sustainable long-term change to their lifestyles. The final study aimed to assess whether obese women compensate for structured exercise by decreasing their NEAT and thereby impeding weight loss. Thirteen participants were prescribed 1500 kcal*wk-1 of exercise through a structured walking program (4 week supervised followed by 4 weeks unsupervised). The energy expenditure of the walks was quantified using individually-calibrated Polar F4 heart rate monitors. The DLW technique was used to measure TEE. Accelerometry measures were also collected throughout and represented an alternative method of quantifying changes in total daily movement patterns resultant from an increase in energy expenditure through exercise. Compliance with the exercise program was excellent, with the average compliance being 94% over the 8-week intervention. The adoption of moderate-intensity exercise in this group of obese women resulted in a 12% decrease in TEE (p = 0.01) and a 67% decrease in NEAT (p < 0.05). No significant change was observed in resting metabolic rate from baseline to the postintervention time-point. Compensation was significantly correlated with dietary report bias (r= -0.84, p = 0.001), body image (r = 0.75, p < 0.01), and bodily pain (r = -0.65, p < 0.05). A linear regression model including dietary reporting bias and the pain score explained 78% of the variation in ΔTEE. Compensators were therefore less likely to underreport their dietary intake, less likely to be self-aware of their obese state, and more likely to be experiencing pain in their daily life. Self-reported dietary intake decreased significantly during the intervention (p = 0.01) with specific decreases noted in fat and carbohydrate intake. The consequence of compensation was evidenced by a lack of significant change in body weight, body composition, or blood lipids (p > 0.05). However, positive outcomes of the study included improvement in the SF-36 scores of general health (p < 0.05) and maintenance of exercise program adherence into the unsupervised phase of the intervention. Qualitative data collected via interview indicated that 85% of participants experienced increased energy and positive feedback from peers during the intervention. This study confirms that exercise prescription needs to be prescribed with an individualised approach that takes into account level of adiposity. The goal of exercise prescription for the obese should therefore be to determine the intensity and modality of exercise that does not activate compensatory behaviours, as this may in turn negate the beneficial effects of the additional energy expenditure of exercise. This study confirms that during the initial phase of an exercise-based weight loss intervention, the majority of obese women compensated for some, if not all, the energy cost of the exercise sessions by reducing NEAT. Whether this compensatory behaviour continues beyond the first month of an exercise program, particularly after training adaptations in cardiorespiratory fitness are realised, cannot be discerned from the current study. However these results do provide a rationale for why the magnitude of weight loss achieved is often less than predicted during exercise interventions. Further research is required to examine the temporal pattern of compensation in NEAT, and the relationship between the time courses of NEAT compensation relative to physical fitness improvements. The results from this thesis support the use of activity monitors such as accelerometers during weight loss interventions to track NEAT and provide objective feedback regarding compensatory behaviours to clinicians and the obese individuals.

The prevalence of obesity continues to increase despite considerable research and innovation regarding treatment and management strategies. When completed as prescribed, exercise training is associated with numerous health benefits and predictable levels of weight loss. However, under free-living conditions the benefits of exercise are less consistent, suggesting that non-adherence and/or a compensatory response in non-exercise activity thermogenesis (NEAT) may be occurring. The accurate quantification of all components of total energy expenditure (TEE), including TEE itself, was imperative to elucidate the primary research question relating to the impact of exercise on TEE. In addition, the measurement of changes in body composition and the response to prescribed exercise were assessed in methodological and pilot investigations. Following this extensive background, the primary research question relating to the effect of exercise on levels of TEE and the associated implications of such a compensatory response could be more rigorously investigated. The first study investigated the variability in isotopic equilibrium time under field conditions, and the impact of this variability on estimates of total body water (TBW) and body composition when using the deuterium dilution technique. Following the collection of a fasting baseline urine sample, 10 women and 10 men were dosed with deuterium oxide (0.05g/kg body weight). Urine samples were collected every hour for 8 hours. The samples were analysed using isotope ratio mass spectrometry and time to equilibration was determined using three commonly employed data analysis approaches. Isotopic equilibrium was reached by 50, 80 and 100% of participants at 4, 6 and 8 h, respectively. The mean group equilibration times determined using the three different plateau determination methods were 4.8 ± 1.5, 3.8 ± 0.8, and 4.9 ±1.4 h, respectively. Isotopic enrichment, TBW, and percent body fat estimates differed between early sampling times (3-5 h), but not later sampling times (5-8 h). Therefore, sampling < 6 hours post dose compared to sampling ≥ 6 hours resulted in greater relative measurement error in TBW and body composition estimates. Although differences in equilibration time were apparent between the three plateau determination approaches, sampling at 6 hours or later may decrease the likelihood of error in body composition estimates resultant from incomplete isotopic equilibration in a small proportion of individuals. In the second study, the aim was to measure the self-paced walking (SPW) speed of adults ranging in body size from normal to obese. The utility of heart rate monitors to estimate the energy cost of walking was also investigated. Twenty-nine participants (12 normal-weight, 17 overweight or obese) completed two outdoor walking tests to determine their SPW speed. A walking treadmill test with stages below, at, and above the SPW speed was completed to compare the energy expenditure estimates of the Polar S610 and WM42 heart rate monitors with that from indirect calorimetry. The average SPW speed was 1.7 ± 0.1 m*sec-1, which was equivalent to an exercise intensity of 48.6 ± 9.4 %VO2max (61.0 ± 7.1 %HRmax). There was no difference in the energy expenditure estimation between indirect calorimetry (4.7 ± 0.7 kcal*kg*-1*h-1), the S610 (4.8 ± 1.3 kcal*kg*-1*h-1) and the WM42 (4.8 ± 1.6 kcal*kg*-1*h-1). It was concluded that the heart rate monitors provided reasonable energy expenditure estimates at the group level. However considerable error was evident at the individual level, explained in part by exercise heart rate and fitness level, suggesting that an individualised calibration should be performed where possible. An additional finding from this study was that 145 to 215 minutes of SPW per week, dependent upon the level of adiposity, is required to meet the current American College of Sports Medicine (ACSM) guidelines for health of 1000 kcal*wk-1. The purpose of the third study was to establish the level of adherence to a specific exercise prescription (1500 kcal*wk-1) by objectively quantifying unsupervised exercise energy expenditure (ExEE) in a group of obese women. The 16-wk lifestyle intervention consisted of weekly meetings with research staff, combined with promotion of increased ExEE (1500 kcal*wk-1) and a decreased dietary intake (-500 kcal*d-1). Twenty-nine obese females (Body Mass Index = 36.8 ± 5.0 kg*m2, Body Fat = 49.6 ± 3.7 %) from a hospital-based lifestyle intervention were included in the analysis. ExEE was estimated and monitored weekly using heart rate monitoring. Body composition was measured before and after the intervention by dual-energy x-ray absorptiometry (DXA). Results indicated free-living adherence to the exercise prescription was modest and variable, with 14% of participants achieving the 1500 kcal*wk-1. The average weekly ExEE (768 kcal*wk-1) represented 51.2% of the total amount prescribed. ExEE was correlated with changes in body weight (r = 0.65, p < 0.001) and fat mass (r = 0.65, p = 0.0002). Achievement of a 5% weight loss target was dependent on an ExEE level of 1000 kcal*wk-1 (p <0.001). Exercise 'adherers' (> 000 kcal*wk-1) lost more weight (-9.9 vs. -4.1 kg), more fat mass (-6.8 vs. -3.0 kg), and more waist circumference (-9.8 vs. -5.6 cm) when compared to 'non-adherers' (< 1000 kcal*wk-1). The results suggest that the extent of supervision and monitoring influenced exercise adherence rates. The variability in adherence highlights the importance of objective monitoring of ExEE. Identification of individuals not complying with program targets may enable intervention staff to provide additional support or make individualised adjustments to the exercise prescription. The fourth study investigated issues relating to the management and interpretation of accelerometry data when the device is to be used to monitor levels of daily physical activity. Given the high between-individual variability in accelerometry output for a given walking speed, the use of a more individualised approach to the data management has been suggested. In addition, accelerometry was used to compare daily physical activity patterns between a supervised and unsupervised exercise prescription of the same dose (1500 kcal*wk-1) in overweight and obese women. Total energy expenditure, activity energy expenditure, and vector magnitude increased significantly during the intervention. Time spent in very low intensity movement decreased from baseline to the intervention (p < 0.01) in both the supervised (-18.6 min*d-1) and unsupervised (-68.5 min*d-1) group, whereas time spent in high and vigorous intensity movement increased significantly from baseline to the intervention (p < 0.05 and p < 0.0001, respectively). The increase in vigorous movement was significantly greater in the supervised group when compared to the unsupervised group (+11.5 vs. +5.4 min*d-1, p < 0.05). Time spent above three different moderate-intensity walking thresholds increased from baseline to the intervention (p < 0.0001). The threshold determination approach significantly affected the resultant outcomes (p < 0.0001) such that the standard threshold was significantly different to both group-specific and individualised approaches. Significant differences were also noted in accelerometer output between treadmill and overground walking (p < 0.0001). A positive finding of this study was that two different interventions aimed at increasing physical activity levels in a group of sedentary and obese women were successful in gaining modest increases in overall daily movement. The change observed appears to be a replacement of sedentary movement with more vigorous physical activity. Collectively, the differences observed between threshold determination approaches, as well as between treadmill and overground walking, highlight the need for standardised approaches to accelerometry data management and analysis. In addition, the findings suggest that obese women may benefit from a certain degree of exercise supervision to ensure compliance, however, strategies to encourage these women to continue with the exercise on their own without supervision are essential to making a sustainable long-term change to their lifestyles. The final study aimed to assess whether obese women compensate for structured exercise by decreasing their NEAT and thereby impeding weight loss. Thirteen participants were prescribed 1500 kcal*wk-1 of exercise through a structured walking program (4 week supervised followed by 4 weeks unsupervised). The energy expenditure of the walks was quantified using individually-calibrated Polar F4 heart rate monitors. The DLW technique was used to measure TEE. Accelerometry measures were also collected throughout and represented an alternative method of quantifying changes in total daily movement patterns resultant from an increase in energy expenditure through exercise. Compliance with the exercise program was excellent, with the average compliance being 94% over the 8-week intervention. The adoption of moderate-intensity exercise in this group of obese women resulted in a 12% decrease in TEE (p = 0.01) and a 67% decrease in NEAT (p < 0.05). No significant change was observed in resting metabolic rate from baseline to the postintervention time-point. Compensation was significantly correlated with dietary report bias (r= -0.84, p = 0.001), body image (r = 0.75, p < 0.01), and bodily pain (r = -0.65, p < 0.05). A linear regression model including dietary reporting bias and the pain score explained 78% of the variation in ΔTEE. Compensators were therefore less likely to underreport their dietary intake, less likely to be self-aware of their obese state, and more likely to be experiencing pain in their daily life. Self-reported dietary intake decreased significantly during the intervention (p = 0.01) with specific decreases noted in fat and carbohydrate intake. The consequence of compensation was evidenced by a lack of significant change in body weight, body composition, or blood lipids (p > 0.05). However, positive outcomes of the study included improvement in the SF-36 scores of general health (p < 0.05) and maintenance of exercise program adherence into the unsupervised phase of the intervention. Qualitative data collected via interview indicated that 85% of participants experienced increased energy and positive feedback from peers during the intervention. This study confirms that exercise prescription needs to be prescribed with an individualised approach that takes into account level of adiposity. The goal of exercise prescription for the obese should therefore be to determine the intensity and modality of exercise that does not activate compensatory behaviours, as this may in turn negate the beneficial effects of the additional energy expenditure of exercise. This study confirms that during the initial phase of an exercise-based weight loss intervention, the majority of obese women compensated for some, if not all, the energy cost of the exercise sessions by reducing NEAT. Whether this compensatory behaviour continues beyond the first month of an exercise program, particularly after training adaptations in cardiorespiratory fitness are realised, cannot be discerned from the current study. However these results do provide a rationale for why the magnitude of weight loss achieved is often less than predicted during exercise interventions. Further research is required to examine the temporal pattern of compensation in NEAT, and the relationship between the time courses of NEAT compensation relative to physical fitness improvements. The results from this thesis support the use of activity monitors such as accelerometers during weight loss interventions to track NEAT and provide objective feedback regarding compensatory behaviours to clinicians and the obese individuals.

Smokers who successfully quit smoking gain weight; although important factors have been identified the mechanisms remain unclear. We measured changes in body weight, fat distribution, and dietary intake of macronutrients during a 26 week smoking cessation trial with the use of nicotine and placebo patch in a Hispanic sample of smokers (88% Mexican-American). Participants were randomized to receive patch treatment for 10 weeks and then followed for 16 weeks. We found that nicotine treated quitters experienced significantly less weight gain than placebo treated quitters at 6 weeks; however by 26 weeks, there were no significant differences among treatment groups. We found that percent total body fat (%TBF) for nicotine treated female quitters changed significantly less than for placebo treated female quitters at 10 weeks (p<0.05); there were no treatment differences in change in %TBF for males at 10 weeks. Male and female quitters experienced significantly less change in %TBF at 26 weeks than continued smokers (adjusted for treatment). Dietary intake of total energy, percent of total energy consumed as fat, protein, and carbohydrate were not significantly different by treatment group from BL for males or females. Thus, although body weight increased significantly in quitters versus non-quitters; dietary intake of macronutrients did not change significantly from BL for quitters and non-quitters. This suggests that factors other than changes in energy intake are responsible for the weight gain observed in this sample of Hispanic ex-smokers.

Orientadores: Denise Vaz de Macedo, Armindo Antonio Alves
Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
Made available in DSpace on 2018-08-06T19:50:53Z (GMT). No. of bitstreams: 1 Gandra_PauloGuimaraes_M.pdf: 2519156 bytes, checksum: 95614e6d3c6f42975590f551e27382d2 (MD5) Previous issue date: 2006
Resumo: O objetivo central deste trabalho foi analisar a variação da capacidade antioxidante total, conferida por antioxidantes de baixo peso molecular (ABPM) em fluidos biológicos e tecidos, através do uso da voltametria de pulso diferencial (VPO). O capítulo 1 corresponde a um artigo de revisão sobre as possíveis fontes de geração de espécies reativas de oxigênio no músculo esquelético durante o exercício físico. O capítulo 2 é um artigo de divulgação, cujo objetivo é fornecer subsídios para a análise da capacidade antioxidante total de amostras biológicas conferida por ABPM para acompanhar a modulação do sistema de defesa antioxidante em função do treinamento físico. Para tanto, são discutidos o uso da voltametria cíclica e a possibilidade do uso de outras técnicas voltamétricas, como a VPO. O artigo contido no capítulo 3 apresenta dados da concentração de ABPM no plasma e na saliva de atletas submetidos a um período de treinamento físico. Observou-se, nesse estudo, uma diminuição da capacidade antioxidante total do plasma após 6 semanas de treinamento (879.28 :t 197.92 j..Imol Trolox equiv. L-1 na segunda semana versus 787.82 :t 154.71 j..Imol Trolox equiv. L-1 na sétima semana). Essa diminuição foi associada a um aumento no desempenho em testes físicos específicos e à manutenção das concentrações de marcadores de lesão muscular e de processo inflamatório, sugerindo que uma diminuição na capacidade antioxidante plasmática faz parte do estágio inicial de adaptação ao treino. As capacidades antioxidante da saliva e do plasma apresentaram correlação entre si (r=O.5871, pAbstract: The objective of this study was to analyze the changes in total antioxidant capacity conferred by low molecular weight antioxidants (LMWA) in biological fluids and tissues by the use of differential pulse voltammetry (DPV). Chapter 1 is a review article about the possible fonts of reactive oxygen species generation in skeletal muscle during exerci se. Chapter 2 is a divulgation article that deals with antioxidant defense systems, LMWA detection methods, cyclic voltametry and DPV. The paper in chapter 3 presents the results about LMWA concentration in plasma and saliva of athletes submitted to physical training. It was observed a decrease in plasma total antioxidant capacity after 6 weeks of training (879.28 :t 197.92 !-Imol Trolox equiv. L-1 in second week versus 787.82:t 154.71 !-Imol Trolox equiv. L-1 in seventh week) associated to an enhanced physical performance in specific tests and maintained indices of muscle damage and inflammation. The data suggests that a small decrease in the plasma antioxidant capacity is part of a normal answer in the initial stages of a physical training programo It was also shown in this study a significant correlation between plasma and saliva antioxidant capacity (r=0.5871, p<0.01) and a significant correlation between this samples antioxidant capacity and their respective urate concentrations. In chapter 4 the kinetics of liver and skeletal muscle hydrophilic and lipophilic LMWA and enzymatic antioxidants from rats submitted to exhaustive exerci se preceded by 24h of fasting, are shown. Liver and muscle hydrophilic extractions and liver lipophilic extraction presented two classes of LMWA while muscle lipophilic extraction presented only one class. It was observed a significant decrease in the antioxidant capacity conferred by hydrophilic and lipophilic LMWA and enzymatic antioxidants in ali analyzed moments (30 min, 1, 6 e 24 h). Only one class of muscle hydrophilic LMWA showed to be reestablished 24h after exerci se. Liver lipophilic first and second classes of LMWA were increased in 57% and 42% respectively after fasting. Enzymatic antioxidants activities were also reduced during the whole analyzed period, presenting a strong correlation with the antioxidant capacity conferred by LMWA. These is the first report of the use of differential pulse voltammetry for total antioxidant capacity determination conferred by LMWA of biological fluids as plasma and saliva and tissues like liver and skeletal muscle
Mestrado
Bioquimica
Mestre em Biologia Funcional e Molecular

Background: Impaired glucose tolerance and diabetes mellitus are increasingly recognised in survivors of bone marrow transplantation and total body irradiation (BMT/TBI). Aim: To investigate mechanisms leading to increased risk of diabetes in childhood survivors of acute lymphoblastic leukaemia (ALL) treated with BMT/TBI. Method: Childhood ALL survivors treated with BMTITBI (1 0-14.4Gy) (Group1, n=20,1 OM) were compared with a chemotherapy only Group 2 (n=28, 11 M), and an obese otherwise healthy Group 3 (n=22,7M). All were aged 16-26 and had assessments of metabolic profile (auxology, blood pressure, lipids, adipocytokines), insulin sensitivity (oral glucose tolerance tests), ~-cell function (arginine intravenous glucose tolerance tests), body composition [Dual energy X-Ray absorptiometry scan (DEXA) and magnetic resonant imaging(MRI)] and pancreatic volume (MRI). Results: Group1 had a higher prevalence of abnormal glucose tolerance and hypertriglyceridaemia than Groups 2 and 3; and reduced high density lipoprotein and abnormal insulin sensitivity compared with Group 2. In Group 1, metabolic abnormalities were not associated with body mass index, but with waist-to-hip ratio. Group 1 showed lower insulin secretion adjusted for insulin sensitivity than Groups 2 and 3. Size adjusted pancreatic volume was smaller in Group 1 than Groups 2 or 3. Group 1 had a higher prevalence of reduced fat-free mass than Groups 2 and 3, and lower mean lean mass index than Group 3. Group 1 showed lower total and truncal fat masses, but no difference in android-to-gynoid ratio than Group 3. Group 1 showed a higher visceral and intramuscular, but lower percentage and overall distribution of subcutaneous fat compared with Groups 2 and 3. Insulin sensitivity was lower for the same degree of central fat mass in Group 1. Adiponectin levels were lower in Group 1 than 2 and correlated negatively with time post BMT/TBI. Conclusions: Reduced ~-cell reserve with smaller pancreatic volume, reduced insulin sensitivity with higher visceral and intramuscular, and reduced subcutaneous fat distribution contribute to the increased risk of abnormal glucose tolerance in BMTITBI survivors.

Forty-five obese postmenopausal Caucasian women were treated with phentermine hydrochloride (Fastin®) and a 1200 kcal diet for weight reduction. Total and regional body composition changes were measured by dual-energy X-ray absorptiometry (DXA) and by anthropometry at 3-mo intervals over 9 mo. Plasma lipids, and serum insulin and leptin were measured. After 3 mo, Fastin® therapy produced a 6.8 kg weight loss (P < 0.01), and DXA-assessed fat and lean mass losses (P < 0.01) of 11.9 and 3.0%. respectively. DXA-estimated regional composition revealed respective fat mass losses of 14.1 and 11.9%. From abdomen and thighs, suggesting primarily subcutaneous and central fat depot losses. DXA reliability was assessed by same-day duplicate measurements (n = 10) calculated using old (version 8.1a) and new (version 8.21) analysis software. A 1.5% between-duplicate difference in lean mass was obtained with the old software; the new software yielded 1.1, 1.4 and 1.6% differences between duplicates for fat, lean and leg lean masses, respectively. CVs ranged from 1.7% for bone mineral content to 12.0% for arm fat mass for both versions. The new software produced higher values for all variables, except arm fat and lean masses than the old software. Except for a 1.9% trunk fat loss detected with the old software, magnitude of body composition changes over 3 mo in 21 weight-stable subjects was the same. The new software estimated total weight more accurately and with less variability than the old software. Fastin®-treated women lost (P < 0.01) 10% of their baseline body weight over 9 mo which correlated with a 20% reduction (P < 0.01) in serum leptin concentration. Plasma HDL-cholesterol concentration increased (P < 0.01) by 15% over 9 mo while total- and LDL-cholesterol and triglycerides decreased 14.2 (P < 0.01), 25.4 (P < 0.01) and 12.2% (P < 0.05), respectively. Serum insulin was unaffected by weight reduction. These data suggest that FastinRTM therapy was effective in reducing weight, and in producing a healthier body fat distribution and plasma lipid profile, thereby lowering cardiovascular disease risk in obese postmenopausal women. The DXA instrument (Holologic QDR-4500A. Hologic Inc. Waltham, MA) gave reproducible estimates of composition change in this population regardless of the software version used.