In radiation therapy, a treatment plan is designed to make the delivery of radiation to a target more accurate, effective, and less damaging to surrounding healthy tissues. In lung sites, the tumor is affected by the patient’s respiratory motion. Despite tumor motion, current practice still uses a static delivery plan. Unexpected changes due to coughs and sneezes are not taken into account and as a result, the tumor is not treated accurately and healthy tissues are damaged. In this thesis we detail a framework of using an accelerometer device to detect and forecast coughs. The accelerometer measurements are modeled as a ARMA process to make forecasts. We draw from studies in cough physiology and use amplitudes and durations of the forecasted breathing cycles as features to estimate parameters of Gaussian Mixture Models for cough and normal breathing classes. The system was tested on 10 volunteers, where each data set consisted of one 3-5 minute accelerometer measurements to train the system, and two 1-3 minute accelerometer measurements for testing.

This study examined the effects of temperature and chronic hypoxia (CH) on pH/CO2- sensitive fictive breathing, and central pH/CO2 chemosensitivity, in cane toads (Bufo marinus). Toads were exposed to CH (10% or 15% O2) or control conditions (21% O2) for 10 days at either room temperature (controls), 10°C or 30°C following which in vitro brainstem-spinal cord preparations were used to examine central pH/CO2-sensitive fictive breathing (i.e., motor output from respiratory nerves which is the neural correlate of breathing). A reduction in artificial cerebral spinal fluid (aCSF) pH increased fictive breathing frequency (fR) and total fictive ventilation (TFV). Cold temperature reduced and hot temperature increased fR and TFV under control conditions. CH attenuated fictive breathing independently of temperature. Additional experiments in which the aCSF temperature was varied indicate that the effects of temperature acclimation result from neural plastic changes within respiratory control centres in the brain.

ABSTRACT DESIGN OF A CONNECTED PIPE TEST FACILITY FOR RAMJET APPLICATIONS SARISIN, Mustafa Nevzat M.S., Department of Mechanical Engineering Supervisor: Asst. Prof. Dr. Abdullah ULAS Co-Supervisor: Prof. Dr. Kahraman ALBAYRAK April 2005, 164 pages Development of the combustor of a ramjet can be achieved by connected pipe testing. Connected pipe testing is selected for combustor testing because pressure, temperature, Mach number, air mass flow rate can be simulated by this type of testing. Real time trajectory conditions and transition from rocket motor (booster) to ramjet operation can also be tested. The biggest advantage of connected pipe testing is the low operation cost and simplicity. Air mass flow rate requirement is less than the others which requires less air storage space and some components like supersonic nozzle and ejector system is not necessary. In this thesis, design of a connected pipe test facility is implemented. Three main systems are analyzed / air storage system, air heater system and test stand. Design of air storage system includes the design of pressure vessel and pressure &amp / flow regulation system. Pressure and flow regulation system is needed to obtain the actual flow properties that the combustor is exposed to during missile flight. Alternatives for pressure and air mass flow rate regulation are considered in this study. Air storage system designed in this thesis is 27.8 m3 at 50 bar which allows a test duration of 200 seconds at an average mass flow rate of 3 kg/s. Air heater system is utilized to heat the air to simulate the aerodynamic heating of the inlet. Several different combustion chamber configurations with different flame holding mechanisms are studied. The most efficient configuration is selected for this study. Combustion analysis of the air heater is performed by FLUENT CFD Code. Combustion process and air heater designs are validated using experimental data. Designed air heater system is capable of supplying air at a temperature range of 400-1000 K and mass flow rate range of 1.5-8 kg/s at Mach numbers between 0.1-0.5 and pressure between 2-8 bar. Finally the design of the test stand and ramjet combustor analysis are completed. 3D CAD models of the test stand are generated. Ramjet combustor that will be tested in the test setup is modeled and combustion analysis is performed by FLUENT CFD Code. The ramjet engine cruise altitude is 16 km and cruise Mach number is 3.5. Key-words: Air Breathing Engines, Ramjet, Connected Pipe, Direct Connect, Vitiator.

Methadone is a long acting mu-opioid and is the most effective treatment for heroin addiction. However, opioids depress respiration and methadone maintenance treatment (MMT) patients have a higher mortality rate than the general population. Teichtahl et al conducted a pilot study and found 6 out of 10 MMT patients had central sleep apnea (CSA). But no definite conclusions were made regarding the prevalence and possible pathogenesis of CSA in the patients due to the small sample size and lack of blood toxicology data. The present project aims to confirm the preliminary results and further quantify the sleep disordered breathing (SDB) in stable MMT patients and to delineate the pathogenesis involved. (For complete abstract open document)

The increased work of breathing associated with intense cycling has been identified as a factor that may negatively affect cycling performance. The aerodynamic position, abnormal respiratory mechanics either at rest or during exercise, and the development of a tachypnoeic breathing pattern are factors known to increase the work of breathing. Breathing pattern retraining aims to decrease the work of breathing by delaying the onset of dynamic hyperinflation and the recruitment of accessory breathing muscles. To date no studies have investigated the performance, physiological and perceptual consequences of manipulating breathing pattern in trained cyclists. Purpose: The aim of the present study was to investigate the effect of breathing pattern retraining on 20-km time trial performance and respiratory and metabolic measures in competitive cyclists. Method: Twenty-four competitive male cyclists (age 37.7 ± 8.6 years, mean ± SD; peak 4.34 ± 0.47 L·min-1) were match paired on 20-km time trial performance and assigned at random to either an intervention group (breathing pattern retraining; N = 12) or control group (N = 12). 20-km time trial performance, pulmonary function and the physiological and perceptual response during a maximal incremental cycle step test were assessed pre- and post-intervention. The intervention group underwent four weeks of specific breathing pattern retraining using exercises designed to reduce dynamic hyperinflation and optimise respiratory mechanics. The control group attended the laboratory once a week during this period and performed a 10 minute sub-maximal ride wearing a biofeedback breathing harness. The control group was led to believe the purpose for their participation was to investigate the effect that maximal exercise had on breathing pattern, and to test the reliability of the breathing harness. There was no attempt to modify the breathing pattern of the control group. Data were analysed using an MS Excel spreadsheet designed for statistical analysis. The uncertainty in the effect was expressed as 90% confidence limits and a smallest worthwhile effect of 1.0% was assumed. Results: The intervention group showed substantial improvements in 20-km time trial performance (-1.5 ± 1.1%) and incremental power (3.2 ± 3%). Additionally, breathing frequency (-13.2 ± 8.9%; -9.5 ± 8.4%), tidal volume (10.6 ± 8.5%; 9.4 ± 7.6%), inspiratory time (10.1 ± 8%; 9.4 ± 7.7%), breathing RPE (-30 ± 33.9%; -24.7 ± 28.1%) and leg RPE (-27.9 ± 38.5%; -24.7 ± 28.2%) were all positively affected at lactate threshold and lactate turn point. No positive changes were observed in the control group for 20-km time trial performance (0.0 ± 1.0%), incremental power (-1.4 ± 3.5%), breathing frequency (-1.6 ± 8.0%; -2.0 ± 7.9%), tidal volume (0.9 ± 7.2%; 2.9 ± 9.4%), breathing RPE (16.1 ± 50.2%, 24.8 ± 43%) or leg RPE (13.4 ± 39.6%; 19.9 ± 43.2%) . Conclusion: These results provide evidence of the performance enhancing effect of four weeks of breathing pattern retraining in cyclists. Furthermore, they suggest breathing pattern can be retrained to exhibit a controlled pattern, without a tachypnoeic shift, during high intensity cycling. Additionally, these results indicate breathing pattern retraining attenuates the respiratory and peripheral perceived effort during incremental exercise. Key words: Breathing pattern disorders, retraining, blood stealing, cycling, performance, power output, respiratory mechanics, perceived exertion, 20km-TT

CPAP is the most common treatment for moderate to severe sleep apnea in adults. Despite its efficacy, patients’ safety, comfort and compliance are issues to be considered and improved in CPAP design. The issues include condensation, carbon dioxide in inhaled air, humidity and temperature of inhaled air. When a CPAP user breaths deeply, there will be some air not fully expelled and may be driven back into the heated air delivery tube (HADT). An interest has existed in what impacts this so called reverse flow may bring about to the CPAP use. The main objectives of this research are to quantify the reverse flow and its influence on carbon dioxide re-breathing, delivered humidity to the patient and condensation in the HADT. Within this thesis, two computer models of the CPAP system have been constructed on Simulink™ in the Matlab™ environment. One is about the CPAP fluid dynamic performance and carbon dioxide re-breathing and the other is on thermodynamic performance. The models can predict the dynamic behaviour of the CPAP machine. They are able to mimic the breath induced airflow fluctuation, and flow direction changes over wide real working ranges of ambient conditions, settings and coefficients. These models can be used for future analysis, development, improvement and design of the machine. The fluid dynamic and thermodynamic models were experimentally validated and they have proved to be valuable tool in the work. The main conclusions drawn from this study are: • Reverse flow increases when breaths load increases and pressure setting decreases. • Reverse flow does not definitely add exhaled air to the next inhalation unless the reverse flow is relatively too much. • Mask capacity does not influence the reverse flow. • The exhaled air re-breathed is mainly due to that stays in the mask, therefore larger mask capacity increases the exhaled air re-breath and the percentage of exhaled air in next inhalation drops when the breath load increases. • Deep breathing does not significantly change the total evaporation in chamber. • When deep breathing induced reverse flow occurs, condensation occurs or worsens in the HADT near the mask. This happens only when the humidity of the airflow from the CPAP is much lower than that of the exhaled air and the tube wall temperature is low enough for condensation to occur. • The deep breathing and reverse flow do not significantly influence the average inhaled air temperature. • The overall specific humidity in inhaled air is lower under deep breathing. • Mask capacity does not influence the thermal conditions in the HADT and the inhaled air specific humidity. Also the mask capacity does not significantly influences the inhaled air temperature.

Doctor of Philosphy (PhD) / This thesis describes the work carried out during four treks, each over 10-11 days, from 1400m to 5000m in the Nepal Himalaya and further work performed during several two-night sojourns at the Barcroft Laboratory at 3800m on White Mountain in California, USA. Nineteen volunteers were studied during the treks in Nepal and seven volunteers were studied at White Mountain. All subjects were normal, healthy individuals who had not travelled to altitudes higher than 1000m in the previous twelve months. The aims of this research were to examine the effects on sleep, and the ventilatory patterns during sleep, of incremental increases in altitude by employing portable polysomnography to measure and record physiological signals. A further aim of this research was to examine the relationship between the ventilatory responses to hypoxia and hypercapnia, measured at sea level, and the development of periodic breathing during sleep at high altitude. In the final part of this thesis the possibility of preventing and treating Acute Mountain Sickness with non-invasive positive pressure ventilation while sleeping at high altitude was tested. Chapter 1 describes the background information on sleep, and breathing during sleep, at high altitudes. Most of these studies were performed in hypobaric chambers to simulate various high altitudes. One study measured sleep at high altitude after trekking, but there are no studies which systematically measure sleep and breathing throughout the whole trek. Breathing during sleep at high altitude and the physiological elements of the control of breathing (under normal/sea level conditions and under the hypobaric, hypoxic conditions present at high altitude) are described in this Chapter. The occurrence of Acute Mountain Sickness (AMS) in subjects who travel form near sea level to altitudes above 3000m is common but its pathophysiology not well understood. The background research into AMS and its treatment and prevention are also covered in Chapter 1. Chapter 2 describes the equipment and methods used in this research, including the polysomnographic equipment used to record sleep and breathing at sea level and the high altitude locations, the portable blood gas analyser used in Nepal and the equipment and methodology used to measure each individual’s ventilatory response to hypoxia and hypercapnia at sea level before ascent to the high altitude locations. Chapter 3 reports the findings on the changes to sleep at high altitude, with particular focus on changes in the amounts of total sleep, the duration of each sleep stage and its percentage of total sleep, and the number and causes of arousals from sleep that occurred during sleep at increasing altitudes. The lightest stage of sleep, Stage 1 non-rapid eye movement (NREM) sleep, was increased, as expected with increases in altitude, while the deeper stages of sleep (Stages 3 and 4 NREM sleep, also called slow wave sleep), were decreased. The increase in Stage 1 NREM in this research is in agreement with all previous findings. However, slow wave sleep, although decreased, was present in most of our subjects at all altitudes in Nepal; this finding is in contrast to most previous work, which has found a very marked reduction, even absence, of slow wave sleep at high altitude. Surprisingly, unlike experimental animal studies of chronic hypoxia, REM sleep was well maintained at all altitudes. Stage 2 NREM and REM sleep, total sleep time, sleep efficiency and spontaneous arousals were maintained at near sea level values. The total arousal index was increased with increasing altitude and this was due to the increasing severity of periodic breathing as altitude increased. An interesting finding of this research was that fewer than half the periodic breathing apneas and hypopneas resulted in arousal from sleep. There was a minor degree of upper airway obstruction in some subjects at sea level but this was almost resolved by 3500m. Chapter 4 reports the findings on the effects on breathing during sleep of the progressive increase of altitude, in particular the occurrence of periodic breathing. This Chapter also reports the results of changes to arterial blood gases as subjects ascended to higher altitudes. As expected, arterial blood gases were markedly altered at even the lowest altitude in Nepal (1400m) and this change became more pronounced at each new, higher altitude. Most subjects developed periodic breathing at high altitude but there was a wide variability between subjects as well as variability in the degree of periodic breathing that individual subjects developed at different altitudes. Some subjects developed periodic breathing at even the lowest altitude and this increased with increasing altitude; other subjects developed periodic breathing at one or two altitudes, while four subjects did not develop periodic breathing at any altitude. Ventilatory responses to hypoxia and hypercapnia, measured at sea level before departure to high altitude, was not significantly related to the development of periodic breathing when the group was analysed as a whole. However, when the subjects were grouped according to the steepness of their ventilatory response slopes, there was a pattern of higher amounts of periodic breathing in subjects with steeper ventilatory responses. Chapter 5 reports the findings of an experimental study carried out in the University of California, San Diego, Barcroft Laboratory on White Mountain in California. Seven subjects drove from sea level to 3800m in one day and stayed at this altitude for two nights. On one of the nights the subjects slept using a non-invasive positive pressure device via a face mask and this was found to significantly improve the sleeping oxyhemoglobin saturation. The use of the device was also found to eliminate the symptoms of Acute Mountain Sickness, as measured by the Lake Louise scoring system. This finding appears to confirm the hypothesis that lower oxygen saturation, particularly during sleep, is strongly correlated to the development of Acute Mountain Sickness and may represent a new treatment and prevention strategy for this very common high altitude disorder.

Thesis (M.A.)--University of Toronto, 2005.

Diss. (sammanfattning) Uppsala : Univ., 2004. / Härtill 4 uppsatser.

Thesis(M.S.)--Auburn University, 2007. / Abstract. Vita. Includes bibliographic references (p.103-108).