abstract: Physical activity is critical for optimal health and has emerged as a viable option to improve sleep. Moderate- and vigorous-intensity physical activity comparisons to improve sleep in non-exercising adults with sleep problems is limited. The purpose was to determine the effects of moderate- or vigorous-intensity exercise on sleep outcomes and peripheral skin temperature compared to a no-exercise control. The exercise intensity preference also was determined. Eleven women (46.9±7.0 years) not participating in regular exercise and self-reporting insomnia completed a graded maximal exercise test followed by a crossover trial of three randomly assigned conditions separated by a 1-week washout. Participants performed moderate-intensity [MIC, 30 minutes, 65-70% maximum heart rate (HRmax)] or high-intensity (HIT, 20 minutes, 1-minute bouts at 90-95% HRmax alternating with 1-minute active recovery) treadmill walking or a no-exercise control (NEC) on two consecutive weekdays 4-6 hours prior to typical bed time. A dual-function wrist-worn accelerometer/temperature monitor recorded movement and skin temperature from which sleep-onset latency (SOL), sleep maintenance, sleep efficiency, total sleep time (TST), and peripheral skin temperature changes were calculated. Participants self-reported sleep outcomes weekly, enjoyment of exercise the morning after HIT and MIC, and exercise intensity preference upon completing all conditions. Mixed models analysis of variance examined differences between and within conditions controlling for demographic characteristics and habitual physical activity. HIT resulted in up to a 90-minute TST increase on night four (448 minutes, 95% CI 422.4-474.2) compared to nights one-three. MIC nights three (43.5 minutes, 95% CI 30.4-56.6) and four (42.1 minutes 95% CI 29.0-55.2) showed nearly a 30-minute SOL worsening compared to nights one-two. No other actigraphy-measured sleep parameters differenced within or between conditions. Self-reported sleep outcomes, peripheral skin temperature change, and exercise enjoyment between conditions were similar (p>0.05). More participants preferred lower (n=3) to higher (n=1) intensity activities. Early evening high-intensity and moderate-intensity exercise had no effect on sleep outcomes compared to a control in non-exercising adults reporting sleep complaints. Sleep benefits from HIT may require exercise on successive days. Participants indicated partiality for lower intensity exercise. More information on timing and mode of physical activity to improve sleep in this population is warranted. / Dissertation/Thesis / Doctoral Dissertation Physical Activity, Nutrition and Wellness 2016

Although there is an abundance of research investigating the effects of exercise on cognitive function, few studies have investigated acute effects of exercise on performance of tasks involving executive function. Furthermore, the effects of different exercise intensities on multiple tests of executive function have received little attention. The purpose of this study was to examine the acute effects of 20-minutes of stationary cycling exercise at varying exercise intensities on executive function performance and to determine these acute effects immediately following exercise as well as after 10 and 30-minute delays following exercise. University students (N = 88) completed baseline measures of executive function (stop-signal task [SST] and Stroop task [ST]) and a graded cardiovascular exercise test on Visit 1. On Visit 2, participants were stratified by gender and fitness level and randomized to one of four conditions: high-intensity interval training (HIT), high, moderate or low-intensity steady-state exercise performed on a cycle ergometer. The ST and SST were performed immediately following exercise and again at 10- and 30-minutes post-exercise. Immediately following exercise, ST response times were significantly different (p < .05), demonstrating faster response times for the high and moderate intensity exercise (p < .05), while improvements in SST response inhibition were revealed for the HIT (p < .01) condition. At 10-minutes post-exercise, moderate and low-intensity conditions revealed improvements in ST response times (p <.05), with enhanced SST response inhibition evident in the HIT, moderate and low-intensity conditions (p < .05). At 30-minutes post-exercise, ST response times continued to show improvements from baseline for the moderate and low-intensity conditions (p < .05), while SST response inhibition trended back towards baseline levels (p > .05). The present outcomes demonstrate beneficial effects of exercise, regardless of intensity, for up to 38 minutes post-exercise. Future research should focus on mechanisms that would account for these effects and factors that support enhanced executive function performance with exercise training. / Thesis / Master of Science (MSc)

Competition often requires teams that reside at sea level to compete against opponents whose residence is at a moderate altitude. This may pose a potential competitive disadvantage considering that moderate altitude may cause decrements in VO2max, distance covered, and time to exhaustion in endurance athletes. The purpose of this study was to examine the effect of altitude on game performance measures. Six NCAA Division I female soccer players (20.33 ± 1.21 y; 168 ± 6.45 cm; 62.5 ± 6.03 kg) were retrospectively examined. Comparisons were made between two competitions that were played at sea level (SL) within two weeks of a game played at a moderate altitude (1840 m) on game characteristics including high intensity running (HIR) and total distance covered (TDC). Analysis was performed on these six players who met a threshold of playing sixty or more minutes in each competition. A 10-Hz global positioning system (GPS) was used to measure distance and velocity. The rate of TDC and HIR during the game (m?min-1) and percentage of time at HIR during competition were evaluated. The two games at SL were averaged to establish baseline performance and the mean results were compared with the single game played at altitude. Paired samples t-tests were performed to determine if any mean differences existed between performance at altitude and sea level. Significant differences (p < 0.05) were seen in minutes played between the games at SL (74.23 ± 2.93 min) versus altitude (83.24 ± 5.27 min). The relative distance rate during the game at altitude was lower at altitude (105.77 ± 10.19 m?min-1) than at SL (120.55 ± 8.26 m?min-1). HIR rate was greater at SL (27.65 ± 9.25 m?min-1) compared to altitude (25.07 ± 7.66 m?min-1). The percent of time spent at high intensity was not significantly different (p = 0.064), yet tended to be greater at sea level (10.4 ± 3.3%) than when they performed at altitude (9.1 ±2.2%). Soccer performance at a moderate altitude appears to reduce the rate at which players run throughout the competition, as well as their rate at a high intensity. Results suggest that teams that reside at SL may be at a competitive disadvantage when competing at altitude.

Yes / Purpose: Raised postprandial triglycerides (TAG) and related oxidative stresses are strongly associated with increased cardiovascular disease (CVD) risk. Acute exercise and strawberry ingestion independently ameliorate postprandial lipid excursions and oxidative stress. However, the combined effects of these lifestyle interventions is unknown. We investigated whether acute exercise and strawberry consumption improved postprandial responses to an oral fat tolerance test (OFTT) in overweight/obese males. Methods: Overweight/obese adult males underwent four separate OFTT (73g fat, 33g carbohydrate) with blood sampled at baseline and hourly for 4 h after OFTT. Two OFTT contained 25g freeze-dried strawberries and two contained strawberry flavouring (placebo). Participants performed 40 minutes of submaximal high intensity interval cycling exercise (HIIE) 16 h before one strawberry and one placebo OFTT, and rested before the remaining two OFTT. Serum TAG was analysed and TAG area under curve (AUC) and incremental AUC (iAUC) were calculated. Oxidative stress markers were measured at baseline and 4 h. Differences between conditions (strawberry/placebo and exercise/rest) were assessed using repeated measures ANOVA. Results: Ten males (Age, 31.5 IQR 17.8 years; BMI, 29.9 ±1.8 kg.m-2) completed the study. TAG AUC was 1.5 mmol.4h-1.L-1 lower for the exercise conditions compared to the rest conditions (95% confidence interval [CI]= -2.3 to 0.8, p= 0.001). TAG AUC was not different between the strawberry and placebo conditions (CI= -1.3 to 0.6, p= 0.475). TAG iAUC was 0.5 mmol.4h-1.L-1 greater for the strawberry compared to the placebo conditions (CI= 0.1 to 1.0, p= 0.021). There were no changes in markers of lipid related oxidative stress (P> 0.05). Conclusion: Acute submaximal HIIE appears effective in reducing postprandial lipaemia in overweight/obese adult males. However, strawberry ingestion did not improve postprandial TAG.

Background: Histotripsy is a non-thermal, non-invasive high-intensity focused ultrasound (HIFU) ablative technique that causes mechanical fragmentation of tissue, resulting in liquefied acellular debris with histologically clear demarcated boundaries between treated and non-treated tissues. The acellular debris may include tumor antigens with preserved immunogenicity and the potential to generate systemic immune response against tumor cells. Soft tissue sarcomas (STS) are a common form of cancer in dogs with biological behavior similar to STS in humans. Long-term tumor control requires complete removal with extensive surgical resection, which in many cases is not feasible. As a result, there is need for alternative therapies. Objectives: The primary objective of this study was to demonstrate safety and feasibility of histotripsy in a small animal model of spontaneous STS. The secondary objective was to characterize the impact of histotripsy on the immunologic response. Materials and methods: Pet dogs diagnosed with spontaneous STS were recruited. CT scan of the chest, abdomen, and the tumor was performed for staging and treatment planning. Pretreatment biopsies were obtained. Safety was monitored with physical examinations, owner reports, and CBC/serum biochemistry. Partial tumor ablation was performed using a 500 kHz prototype histotripsy system. A spherical treatment zone of up to 3 cm diameter in each tumor was treated with histotripsy according to the patient-specific treatment plan using 1-2 cycle pulses applied at a pulse repetition frequency (PRF) of 500 Hz. Anatomical ablation zones were evaluated with contrast CT at 1- and 4-days post-treatment, with tumor resection at 4-6 days post-treatment. Tumor microenvironment (TME) gene expression was evaluated with the Nanostring Canine IO panel, and the systemic immune response was evaluated using multiplex serum cytokine levels. Results: Ten dogs were recruited and treated. Tumor histologies included 3 grade III STS, 4 grade II STS, 2 grade I STS, and 1 malignant mesenchymoma. Six dogs were alive, three dogs were euthanized due to disease progression, and one dog was lost to follow up. Histotripsy-related complications were generally self-limiting, with only one patient having increased cutaneous injury score from 1 to 2 (scale 1-5) post-treatment, likely due to prefocal cavitation at the skin. No significant adverse events impacting patient outcome were noted in any of the patients. Visible histotripsy cavitation bubble clouds were seen on real-time ultrasound imaging in nine of ten treatments. Post-treatment histopathology indicated sharply defined regions of ablation that were clearly identifiable grossly and histologically in all samples. Treatment zones were characterized by loss of cell viability, hyalinization, and acute hemorrhage. Post-treatment contrast-enhanced CT images revealed clear, demarcated regions of histotripsy ablated tissue in seven of ten patients. Differential gene expression analysis identified 79 genes with at least 2-fold change following treatment. Genes associated with inflammation, immune cell migration, and immune cell interactions were the highest upregulated. Amongst the gene set analyses, the myeloid compartment gene sets obtained the highest significance score. There were no statistically significant differences between pre- and post-treatment cytokine concentrations for any of the analytes. Conclusions: Histotripsy can achieve safe and effective tumor ablation in dogs diagnosed with STS. Histotripsy induced pro-inflammatory changes within the tumor microenvironment. Histotripsy as an immunotherapeutic treatment option needs to be further investigated. Histotripsy has a potential to be a precise, non-invasive treatment for canine STS. / Master of Science / Histotripsy is a non-thermal high-intensity focused ultrasound (HIFU) ablative technique that uses controlled acoustic cavitation to cause mechanical fragmentation of tissue. To date, there are no reports investigating histotripsy for the treatment of soft tissue sarcoma (STS). This study aimed to investigate the in vivo feasibility of ablating STS with histotripsy and to characterize the impact of partial histotripsy ablation on the acute immunologic response in canine patients with spontaneous STS. CT of the chest, abdomen, and the tumor was performed for staging and treatment-planning. Pretreatment biopsies were obtained. Safety was monitored with physical examinations, through owner reports, and CBC/serum biochemistry. A custom 500 kHz histotripsy system was used to treat ten dogs with naturally occurring STS. Anatomical ablation zones were evaluated with contrast CT at 1- and 4-days post-treatment, with tumor resection at 4-days post-treatment. Safety was determined by monitoring vital signs during treatment and post-treatment physical examinations, routine lab work, and owners' reports. Ablation was characterized using radiologic and histopathologic analyses. Systemic immunological impact was evaluated by measuring changes in cytokine concentrations, and tumor microenvironment changes were evaluated by characterizing changes in infiltration with tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs) using multiplex immunohistochemistry and differential gene expression. Results showed histotripsy ablation can achieve safe and effective tumor ablation in all ten dogs. Immunological results showed histotripsy induced pro-inflammatory changes in the tumor microenvironment. Histotripsy as an immunotherapeutic treatment option needs to be further investigated. Overall, this study demonstrates histotripsy's potential as a precise, non-invasive treatment for STS.

No description available.

Understanding the physiological and behavioural reasons that result in voluntary water intake and the volume subsequently consumed in both the work place and during and following an exercise setting can provide further information on water balance and the necessity and requirements of water intake. The first study (Chapter 3) aimed to assess hydration status in the adult population at the start and end of a working day and the amount of water from beverages that was consumed. Urine osmolality and urine specific gravity (USG) suggested a large proportion of subjects arrived (osmolality: 54%; USG: 53%) and left (osmolality: 35%; USG: 33%) work in a hypohydrated state, with variation between subjects in the same and different places of work. Reported water intake varied between groups with males consuming more than females. To further examine hydration status it was proposed to assess the use of capillary blood sampling as an alternative to more restrictive venous blood sampling (Chapter 4), however, despite tracking changes in blood parameters in a similar capacity, the inconsistencies of results suggested capillary blood sampling could not be used reliably. The remaining chapters in the thesis examined voluntary water intake. In Chapter 5 this was during and following exercise in the cold. Less water was consumed compared to exercise in a warm environment and there was an indication of a blunted thirst response in the cold. Following high intensity intermittent exercise, more water was voluntarily consumed during a one hour recovery period compared to when continuous exercise of the same average power output was performed (Chapter 6). Following exercise there was increased serum osmolality, serum sodium concentration, plasma vasopressin concentration and blood lactate concentration compared to baseline values. The relative contribution that decreasing blood lactate concentrations and water intake during the recovery period had on serum osmolality could not be determined, so the study in Chapter 7 was carried out. The time period during which voluntary water intake was allowed was manipulated during a recovery period following a period of high intensity intermittent exercise. Allowing water intake for the full hour, the final 30 minutes or not at all, resulted in similar decreases in serum osmolality throughout the duration of the recovery period. A combination of finishing the period of exercise allowing plasma volume restoration, reduction in blood lactate concentration, reduction in serum sodium concentration, a restoration of blood lactate concentration and water intake appeared to contribute to decreased serum osmolality. Sensations of thirst were the main stimulants of voluntary water intake (Chapters 3, 5, 6 and 7), however, following exercise, sensations of thirst resulted in water consumption despite the majority of subjects not losing enough water (>2% body mass loss) to require additional rehydration. In this thesis, it can be concluded that voluntary water intake differs between individuals, between work environments, during and following exercise in different environments and following different exercise intensities. Water intake is generally initiated by sensations of thirst arising from physiological and behavioural mechanisms even in the absence of significant hypohydration and will reduce once satiated.

Whilst high levels of cardiorespiratory fitness and physical activity may protect against cardiometabolic risk factor clustering, evidence suggests these outcomes are below optimal in English youths. Adolescence is a key stage in health behaviours development, and thus represents an opportunity for interventions aiming to improve the cardiometabolic health, fitness and activity levels of this population. Recently, there has been growing interest in the efficacy of low-volume high-intensity interval training (HIT) as a time efficient way of improving health and fitness outcomes in adults. Contrastingly, the effects of low-volume HIT in adolescents remains relatively unknown. The first aim of this programme therefore was to develop a novel school-based low-volume HIT intervention. The second was to determine the effectiveness of this model for improving the cardiometabolic health, cardiorespiratory fitness and physical activity levels of adolescents. Study one examined adolescents’ views towards high-intensity exercise, and the proposed low-volume HIT intervention. This data was used to design the novel low-volume HIT model. In Study 2, participants’ heart rate and perceived exertion responses to three prototype prescriptions of low-volume HIT, based on boxing, dance and football were examined. Here, it was indicated that these activities were capable of eliciting a high-intensity training response (~90% of maximum heart rate). Study 3 incorporated the main intervention, which examined the effect of a 10-week multi-activity low-volume HIT intervention (named Project FFAB [Fun Fast Activity Blasts]) on various health and fitness outcomes in adolescents. Here, beneficial effects were detected in the intervention participants compared to the controls for triglycerides, waist circumference, lipid accumulation product and daily moderate-to-vigorous physical activity. Study 4 assessed the fidelity of the intervention, and found that this had been largely upheld. Collectively therefore, it appears that Project FFAB represents a viable strategy for improving aspects of cardiometabolic health and physical activity levels in adolescents.

The IL-6 system is key in the development of chronic low-grade inflammation. It is known to be upregulated in response to acute exercise and lowered at rest after exercise training. IL-6 has both anti- and pro-inflammatory properties and moderation of this cytokine could alleviate chronic low-grade inflammation which is associated with obesity and Type 2 diabetes mellitus (T2DM). This thesis investigated the interplay between inflammation, glycaemic control and high intensity intermittent training (HIIT) - an exercise regimen that has been shown to yield many health benefits. There was a greater increase in IL-6 after an acute bout of HIIT than continuous moderate intensity exercise, where external work was matched (Chapter 4). Although sIL-6R and the IL-6/sIL-6R complex were both significantly increased after acute exercise there were no differences between HIIT and moderate intensity exercise. In response to 2 weeks HIIT there was a significant reduction in IL-6 and increase in IL-6R in adipose tissue in overweight and obese males (Chapter 5). It was also determined that IL-6R present in adipose tissue is at least partly composed of the membrane-bound IL-6R isoform (Chapter 6). Reductions in circulating sIL-6R, the IL-6/sIL-6R complex, MCP-1 and adiponectin, as well as a decrease in waist circumference and increase in peak oxygen uptake during exercise were also induced after 2 weeks HIIT (Chapter 5). Young adults with T2DM (< 40 y) displayed elevated levels of inflammatory proteins in comparison to lean controls, however there were no significant differences in comparison to obese controls (Chapter 7). In conclusion, the findings of this thesis demonstrate that acute and repeated bouts of HIIT have positive effects on the inflammatory profile in the circulation and adipose tissue, particularly in relation to the IL-6 system. It should be determined if HIIT is an achievable mode of exercise for patient populations, including T2DM patients, in order to downregulate the inflammatory profile.

It is possible to reach the radiation-reaction–dominated regime in today’s high-intensity laser facilities, using the collision of a wakefield-accelerated GeV electron beam with a 30 fs laser pulse of intensity 10²² Wcm^-2. This would demonstrate that the yield of high energy gamma rays is increased by the stochastic nature of photon emission: a beam of 10⁹ electrons will emit 6300 photons with energy > 700 MeV, 60 times the number predicted classically. Detecting those photons, or a prominent low energy peak in the electron beam's post-collision energy spectrum, will provide strong evidence of quantum radiation reaction; we place constraints on the accuracy of timing necessary to achieve this. This experiment would provide benchmarking for the simulations that will be used to study the plasmas produced in the next generation of laser facilities. With focused intensities > 10²³ Wcm^-2, these will be powerful enough to generate high fluxes of gamma rays and electron-positron pairs from laser–laser and laser–solid interactions. It will become possible to test the physics of exotic astrophysical phenomena, such as pair cascades in pulsar magnetospheres, and explore fundamental aspects of quantum electrodynamics (QED). To that end we will discuss: classical theories of radiation reaction; QED processes in intense fields; and a Monte Carlo algorithm by which the latter may be included in particle-in-cell codes. The feedback between QED processes and classical plasma dynamics characterises a new regime we call QED-plasma physics.