Whole-body vibration (WBV) was recently introduced as a potential modality for strengthening bones, and this thesis was set out to investigate whether it plays a role in the prevention of postmenopausal bone loss. First, effects of WBV on bone mineral density (BMD) were systematically evaluated in previous randomized controlled trials (RCTs) in postmenopausal women. Second, a RCT of 202 postmenopausal women with primary osteopenia not on bone medications was conducted to investigate the effects of WBV at 0.3g and 90 Hz versus 0.3g and 30 Hz versus controls on various bone outcomes, as measured by dual-energy x-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT), and quantitative ultrasound (QUS). In the systematic evaluation of previous RCTs, statistically significant increase in areal BMD (aBMD) at the hip was found in postmenopausal women receiving WBV versus controls, but the effect was small and may have been due to study bias. Also, WBV was not found to influence aBMD at the lumbar spine or volumetric BMD (vBMD) at the distal tibia in the systematic evaluation. In the RCT conducted in this thesis, no statistically significant effects of WBV were found on aBMD at the femoral neck, total hip or lumbar spine, as measured by DXA, or on vBMD or bone structure parameters at the distal tibia or distal radius, as measured by HR-pQCT. Further in this RCT, a statistically significant decrease was observed in QUS attenuation at the calcaneus in women receiving 90 Hz or 30 Hz WBV compared to controls. This may have been due to heel bone or soft tissue damage, although the effect was small and may not be clinically important. In conclusion, this investigation of postmenopausal women did not find clinically relevant benefits of WBV on osteoporotic-prone skeletal sites, including the hip, spine, tibia or radius, while potentially harmful effects on heel bone and/or soft tissue was observed in response to WBV. Thus based on this thesis, WBV is currently not recommended for the prevention of bone loss in community-dwelling postmenopausal women with primary osteopenia.

Autism and associated gene mutations can be studied with genetic mouse models. Magnetic Resonance Imaging (MRI) of these animal models quantifies the impact of genetics on brain morphology. Using MRI, three genetic mouse models of autism were imaged: Neuroligin 3 R451C knock-in, Methyl-CpG binding protein-2 308-truncation and Integrin β-3 knock-out. Morphological differences were identified using a newly developed MRI mouse cerebellum atlas. The results show all three genes to alter cerebellar anatomy. Each studied gene affected a unique set of cerebellar structures. I hypothesize that the results and known behavioural phenotypes of the models are linked, with anatomy contributing to specific behaviours. In the future work section, a surface-based analysis method is presented to investigate the variance in cerebellum foliation across disease models and inbred strains. This work shows that autism risk-genes alter distinct regions of the cerebellum.

Autism and associated gene mutations can be studied with genetic mouse models. Magnetic Resonance Imaging (MRI) of these animal models quantifies the impact of genetics on brain morphology. Using MRI, three genetic mouse models of autism were imaged: Neuroligin 3 R451C knock-in, Methyl-CpG binding protein-2 308-truncation and Integrin β-3 knock-out. Morphological differences were identified using a newly developed MRI mouse cerebellum atlas. The results show all three genes to alter cerebellar anatomy. Each studied gene affected a unique set of cerebellar structures. I hypothesize that the results and known behavioural phenotypes of the models are linked, with anatomy contributing to specific behaviours. In the future work section, a surface-based analysis method is presented to investigate the variance in cerebellum foliation across disease models and inbred strains. This work shows that autism risk-genes alter distinct regions of the cerebellum.

This study examined right-ventricular-pulmonary arterial (RV-PA) coupling and pulmonary vascular mechanics during acute exercise in 12 middle-aged men with a long-standing history of endurance training. Subjects underwent simultaneous right-heart catheterization and echocardiography, with measures obtained at steady state heart rates of 100, 130 and 150 beats/min. Subjects were highly trained and displayed RV remodeling of endurance-trained athletes. During exercise at 100 beats/min, systolic, diastolic, and mean pulmonary artery pressure increased significantly from rest, as did pulmonary capillary wedge pressure. The slope of pooled mean pulmonary pressure indexed to cardiac output was 1.436 mmHg⋅min-1⋅L-1 with a distensibility index of 0.112 ± 0.048 mmHg-1. The pulmonary arterial elastance-RV end-systolic elastance ratio (Ea:Ees) decreased from rest to exercise at 130 beats/min (P < 0.01). These results suggest that Ea:Ees becomes favourable for RV function during exercise, indicative of a pulmonary vasculature that is highly distensible and well matched to RV output.

The osteoclasts, the bone cells responsible for bone degradation, have a crucial role in the age-related bone loss and post-menopause osteoporosis. Rac1 and Rac2, members of the Rho-family of small GTPases, are known for having a key role in osteoclast formation and activity, which could be translated to bone quality. In this study, we characterize the roles of Rac1 and Rac2 on bone quality using an aged and osteoporotic mouse model. Bones from wild type, Rac1KO and Rac2KO mice were harvested for mechanical tests, bone densitometry, micro-computed tomography and histomorphometric analyses to evaluate bone mineralization and architecture. We observed that the deletion of Rac1 or Rac2 in pre-osteoclasts minimized bone loss in both age-related and post-menopause osteoporosis. These results highlight the importance of the two small GTPases in bone remodeling and identify Rac1 and Rac2 as potential targets for the development of new therapies for the treatment of osteoporosis.

This study explored the current state of eHealth policy in Latin American and the Caribbean (LAC). It is based on a novel methodological approach to the conduct of systematic reviews of documents that are not always published in peer-reviewed journals. 33 countries were included in the study and 19 ICT and 7 eHealth policies were identified. A hybrid inductive and deductive content analysis approach was used to provide an in- depth analysis and comparison of existing national eHealth policies in LAC. The study found that there has been considerable progress in the establishment of ICT policies in the LAC region, but less so for eHealth policy specifically. The findings suggest that the establishment of a strategic framework that may guide and support decisions and choices in the development of national eHealth policies, could prove to be an essential tool in the successful implementation of eHealth in LAC.

Background: Androgen deprivation therapy (ADT) has known adverse effects (AEs). Intermittent (INT) ADT may reduce AEs, improve quality of life, and lower costs compared to continuous (CONT) treatment. Objective: To evaluate the cost-effectiveness of INT vs CONT ADT in men with advanced prostate cancer. Methods: A lifetime Markov individual simulation model was developed to evaluate the incremental cost per quality adjusted life month (QALM) of INT vs CONT ADT. Results: INT dominated CONT ADT (mean total costs $94,460 vs $109,431; mean total QALMs 47.0 vs 46.4). INT ADT resulted in less time on therapy (22.4 vs 56.8 months), fewer hip fractures (0.080 vs 0.093 per patient), and fewer total cases of sexual dysfunction (72.5% vs 87.0% of patients) and cardiovascular disease (38.7% vs 44.6% of patients). Conclusions: These results suggest INT ADT is cost-effective compared to CONT ADT however, differences were small. Additional research is required to confirm these findings.

The osteoclasts, the bone cells responsible for bone degradation, have a crucial role in the age-related bone loss and post-menopause osteoporosis. Rac1 and Rac2, members of the Rho-family of small GTPases, are known for having a key role in osteoclast formation and activity, which could be translated to bone quality. In this study, we characterize the roles of Rac1 and Rac2 on bone quality using an aged and osteoporotic mouse model. Bones from wild type, Rac1KO and Rac2KO mice were harvested for mechanical tests, bone densitometry, micro-computed tomography and histomorphometric analyses to evaluate bone mineralization and architecture. We observed that the deletion of Rac1 or Rac2 in pre-osteoclasts minimized bone loss in both age-related and post-menopause osteoporosis. These results highlight the importance of the two small GTPases in bone remodeling and identify Rac1 and Rac2 as potential targets for the development of new therapies for the treatment of osteoporosis.

This study explored the current state of eHealth policy in Latin American and the Caribbean (LAC). It is based on a novel methodological approach to the conduct of systematic reviews of documents that are not always published in peer-reviewed journals. 33 countries were included in the study and 19 ICT and 7 eHealth policies were identified. A hybrid inductive and deductive content analysis approach was used to provide an in- depth analysis and comparison of existing national eHealth policies in LAC. The study found that there has been considerable progress in the establishment of ICT policies in the LAC region, but less so for eHealth policy specifically. The findings suggest that the establishment of a strategic framework that may guide and support decisions and choices in the development of national eHealth policies, could prove to be an essential tool in the successful implementation of eHealth in LAC.

Background: Androgen deprivation therapy (ADT) has known adverse effects (AEs). Intermittent (INT) ADT may reduce AEs, improve quality of life, and lower costs compared to continuous (CONT) treatment. Objective: To evaluate the cost-effectiveness of INT vs CONT ADT in men with advanced prostate cancer. Methods: A lifetime Markov individual simulation model was developed to evaluate the incremental cost per quality adjusted life month (QALM) of INT vs CONT ADT. Results: INT dominated CONT ADT (mean total costs $94,460 vs $109,431; mean total QALMs 47.0 vs 46.4). INT ADT resulted in less time on therapy (22.4 vs 56.8 months), fewer hip fractures (0.080 vs 0.093 per patient), and fewer total cases of sexual dysfunction (72.5% vs 87.0% of patients) and cardiovascular disease (38.7% vs 44.6% of patients). Conclusions: These results suggest INT ADT is cost-effective compared to CONT ADT however, differences were small. Additional research is required to confirm these findings.