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This diploma thesis is dealing with the concepts behind the Stewart platform based flight simulation phenomena along with the method of inverse kinematics computation. Further, a washout algorithm to provide appropriate vestibular sensing to the pilot and ensuring that platform will not reach its limits is presented. Digital filters designed to be used in the implementation of the washout algorithm and their characteristics are also covered. The last part describes the architecture of the whole system and the implementation of individual parts.

Clinical research in cystic fibrosis (CF) requires study endpoints that are sensitive to airways disease, repeatable and non-invasive. Despite significant advances in the treatment of CF, lung function assessments continue to rely on the forced expiratory volume in 1 second (FEV1). Although simple to perform, it lacks sensitivity, is difficult for younger subjects, and changes over time. An alternative method of assessing lung physiology is to derive measures of ventilation heterogeneity from inert gas washout tests. In early lung disease, measures of gas mixing appear to be more sensitive than spirometry. In addition, since only tidal breathing is required, they are more physiological and are more straightforward for younger subjects. Widespread use has been impaired by the lack of a robust and cost effective gas analyser technology. The work presented in this thesis concerns the adaptation, validation and then use of a novel gas analyser (Innocor) in a clinical system for the performance of multiple breath washouts. Lung clearance index (LCI), a simple measure of ventilation heterogeneity, has been calculated from washouts in 52 adults with CF and 50 healthy controls. LCI was more sensitive to disease than FEV1 in CF, being elevated in 11 of the 12 CF patients with normal spirometry. In healthy subjects, LCI has been shown to be repeatable and reproducible, with a narrow range of normal that is stable over a wide age range. In a separate study of 19 patients, LCI has also been shown to improve with treatment of an exacerbation in CF. Correlation with changes in other biochemical (serum CRP, peripheral blood white cell count, sputum IL-8, sputum neutrophil) clinical (symptom score) or structural (computed tomography) markers was poor. Short term change in LCI has also been demonstrated in CF patients in response to chest physiotherapy, although there was considerable heterogeneity of response in terms of both LCI and volume of lung ventilated by tidal breathing (as measured by washout functional residual capacity). In addition to LCI, multiple breath phase III slope analysis has been performed on washouts of CF patients and healthy controls, and this has been compared to other measures of lung physiology. Proposed measures of convective and diffusive gas mixing have been shown to be unreliable in CF. These studies have also been the first to demonstrate multi-centre use of washout tests as endpoints. The technology described here offers the possibility of a simple and reliable system for performing multiple breath washouts, though at present it is not available commercially. The studies have added to the understanding of the utility and reliability of washout tests, as well as some of their limitations. It is hoped that in future LCI will be an important clinical endpoint in therapeutic intervention studies in CF, and that it will also offer new ways to follow changes in lung physiology in other diseases.

Good motion cueing in a flight simulator serves to enhance the overall simulation environment. However, poor motion cueing can greatly detract from the simulation and serve solely to distract the pilot. The latter was the case for Virginia Tech's three degree-of-freedom motion-base. The most common method of motion cueing is to use washout filters to produce the best motion cues within the physical limitations of the motion system. This algorithm is named the classical washout algorithm and its filters were studied first in this research, but initially yielded undesirable results. In efforts to greatly improve the acceleration response in the pitch axis, the concept of an acceleration feedback controller in conjunction with washout filters was investigated. In developing a mathematical model of the motion-base and its corresponding circuitry, corrections and modifications were made to the circuitry which served to improve the dynamic response of the motion-base and enhance motion sensations. Next, design and implementation of the acceleration feedback controller for the pitch axis was performed and tested using a pilot rating scale and time history responses. The parameters for the acceleration feedback algorithm and the classical washout algorithm were varied to find the most favorable algorithm and set of parameters. Results of this paper have demonstrated the successful implementation of acceleration feedback and that the motion system at Virginia Tech now serves to greatly enhance the simulation environment. / Master of Science

Nasal high flow (NHF) therapy is a recent form of non-invasive respiratory support for patients suffering from respiratory distress that supplies high flows of heated and humidified air, oxygen or a mix via a nasal cannula. A number of in vivo studies have proven its effectiveness at improving blood oxygenation; however, its mechanisms of action remain widely unproven. Two proposed mechanisms of action, the CO2 washout of anatomic dead space and the production of positive airway pressure, are investigated in this thesis for the use of the Fisher & Paykel Healthcare Ltd (FPH) Optiflow™ adult nasal cannula through a range of experiments. Five anatomically correct upper airway models produced from computed tomography (CT) scan data via 3D printing were employed during in vitro experiments and two live subjects participated in in vivo measurements. The human respiratory system was faithfully replicated for CO2 washout experiments with physiological CO2 diffusion into the lung replicated by a constant flow of CO2 into the lung pump. In vivo measurement of a natural breathing flow pattern was scaled to an average population tidal volume and respiratory rate for in vitro use. In vitro measurements of static pressure during natural breathing found similar flow resistances across the nasal passage for inspiratory and expiratory flow directions; however, across the entire upper airway greater resistance was seen for inspiration. Introduction of NHF therapy produced significant increases in all mean and peak airway pressures within the upper airway with a flow rate of 30 LPM fulfilling the inspiratory work requirements presented by the upper airway resistance. In vivo and in vitro hot wire anemometry measurements at the exterior nares indicated low velocity and turbulence intensity flows at peak inspiration and a high velocity jet with high turbulence during peak expiration. At natural breathing an in vitro anterior-posterior velopharynx traverse captured low turbulence intensities during peak inspiration and high turbulence intensities during peak expiration. Introduction of NHF therapy had little influence on the turbulence intensity profile of peak expiration yet did cause significant increases in the turbulence intensities during peak inspiration. Measurements of the CO2 concentration near the lung volume over many breath cycles were used to find time-averaged CO2 concentrations. For the standard airway model an average CO2 concentration of 4.88 ± 0.07 %V/V was determined during natural breathing. Implementation of increasing levels of NHF therapy generated significant washout of CO2 reducing this average concentration to a minimum of 3.81 ± 0.11 %V/V at a flow rate of 80 LPM. It was determined that airway geometry significantly affected the efficacy of the NHF therapy though CO2 washout was observed in all five airway models.

Multiple breath washout (MBW) of inert gas for assessment of airway disease in children is an emerging technique. In many studies Lung Clearance Index (LCI), derived from multiple breath washout of SF6, is more able to detect early or mild lung disease than standard lung function measurements. It is also able to detect very early lung disease in progressive conditions such as Cystic Fibrosis (CF). Where infants born with this condition were thought to have minimal lung disease activity, LCI is higher in these children than healthy controls. Lack of available commercial devices has hampered expansion of this technique to centres other than specialist research teams. Innocor (Innovision, Dk), a photoacoustic mass spectrometer capable of performing multiple breath washout, was adapted within this research group for use in adults. This thesis describes the setup, adaptation and validation of Innocor for use in children. In 4 studies, healthy controls, children with asthma and children with CF were recruited to perform MBW. In one study, 29 healthy controls and 31 children with asthma were recruited. Healthy controls performed 1 set of washouts, establishing a normative range. Children with asthma performed measurements before and after bronchodilator. Results showed increased LCI in children with asthma even though they were clinically stable as defined by symptoms. LCI stayed high even following bronchodilator suggesting evidence of residual airway disease in well controlled asthmatics despite adequate symptom control. To investigate short term variability of MBW measurements, two other studies recruited 18 children with CF in each. They performed measurements before and after standard physiotherapy manoeuvres and during sitting and lying posture. LCI did not change significantly after airway clearance physiotherapy, compared with children who did no intervention. Variability was high in both groups however suggesting CF lung disease is a complex interaction of changing ventilation in adjacent lung units. Lying posture induced greater changes in lung function in children with CF than controls. LCI appears to be more sensitive to this change than standard lung function measurements (spirometry). In another study 32 children with CF were recruited to perform serial lung function measurements over 18 months. These were data collected as part of the UK Cystic Fibrosis Gene Therapy Consortium (CFGTC) clinical studies in preparation for planned gene therapy trials. LCI appears comparable to FEV1 and may be able to detect another aspect of airway disease. All initial studies were performed in older children (>5yrs). The basic Innocor device is unsuitable for testing of younger patients with low breath volume and high respiratory rate. In-house adaptations following detailed lung model experimentation led to a faster analyser response, potentially capable of MBW in younger children. The second part of this thesis concerns lab experiments and an in-vivo comparison with the current gold-standard MBW device, a respiratory mass spectrometer. 16 healthy volunteers and 9 children with CF were recruited. Ages ranged from 0.4 yrs to 49 yrs. Innocor values for lung volume estimation compared favourably with the mass spectrometer. No evidence of bias caused by Innocor error was seen, however intra-test variability was rather high, reducing the precision of the results. These studies indicate Innocor is a robust, simple to use device with potential as a commercial lung function system. Modifications were made to make it suitable for use in all ages. Further development will need to focus on the patient interface and software, which is the domain of the manufacturers. The experiments contained in this thesis are therefore of interest to the wider respiratory research community as well as manufacturers of MBW devices.

The Multiple Breath Washout (MBW) test is increasingly being recognised as a sensitive method of detecting early small airways lung disease. Indices of MBW include lung clearance index (LCI), Scond and Sacin. Factors that affect MBW variability have not been fully established. This thesis presents five studies which examine MBW repeatability in children with and without cystic fibrosis (CF) or asthma. MBW was performed using 0.2% sulphur hexafluoride and the modified Innocor (Innovision). Testing was performed at the Clinical Research Facility of the Royal Hospital for Sick Children in Edinburgh. (1) MBW and spirometry were performed in children with and without CF (n=20 in each group), initially while sitting and then 30 minutes after assuming a supine posture. LCI was found to significantly rise on lying supine in healthy children (p < 0.01) and children with CF (p=0.03). (2) Thirty two children with CF performed MBW and spirometry on four study visits, results were correlated with findings from high resolution chest computed tomography scans taken on the first visit. LCI showed the strongest correlation with extent and severity of bronchiectasis (r=0.66, p < 0.01 and r=0.69, p < 0.01 respectively). Variability of LCI was similar to FEV1 over the 4 visits. (3) MBW and spirometry of 66 healthy children were compared to 63 children with stable asthma; lung function of asthmatic children was related to symptoms and medication use. LCI was higher in the asthmatic group (6.7 vs 6.3, p < 0.01); within the asthmatic group LCI was significantly higher if asthma was less well controlled (p=0.02). (4) Children with and without asthma (n=21 in each group) performed MBW and spirometry before and after exercise and again after salbutamol, symptom data was collected from asthmatic children. Baseline LCI was abnormal in the asthmatic group who had severe exercise induced bronchospasm during testing. (5) Asthmatic children admitted to hospital due to exacerbation performed MBW and spirometry. Mean (SD) LCI was abnormally high at 8.5 (1.7) in the nine patients recruited and returned to normal 6.7 (0.6) in three patients who attended follow up. I have presented evidence that LCI is repeatable and sensitive to early disease in CF and asthma. I have described for the first time the effects of exercise and exacerbation on MBW indices in asthmatic children. MBW is potentially a very useful tool in paediatrics; standardisation of testing and equipment may enable clinical use.

Hurricanes can cause considerable damage along the coastlines of the United States. There are very little data relating hurricanes and sea turtle nesting. Hurricane season (June- November) and sea turtle nesting season, for the study period, (March- September) overlap in Broward County, Florida. This paper examines the relationship between the Hurricane Impact Index (HII) and hatching success of loggerhead sea turtles (Caretta caretta) and HII and washout rate. For ten of the eleven storms studied, there was no significant relationship between HII and hatching success (percent). Tropical Storm Ophelia (2005) showed a significantly higher (p=0.0206) hatching success after the storm’s passing than before the storm’s passing. There was a significant relationship between washout rate and HII (p=0.026).

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22741号 / 医博第4659号 / 新制||医||1046(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 辻川 明孝, 教授 伊達 洋至, 教授 羽賀 博典 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Oryx Simulations produce simulators for mining and forestry machinery used for educational and promotional purposes. The simulators use motion platforms to reflect how the vehicle moves within the simulator. This platform tilts and accelerates the driver in order to enhance the experience. Previously a classical washout filter algorithm has been used to control the platform which leaves something to be desired regarding how well it reflects the vehicles movement, how easy it is to tune and how it handles the limits of the platform. This thesis aims to produce a model that accurately reflects angles, velocities and accelerations while in the mean time respecting the limits of the platform. In addition to this the developed model should be easy to modify and tune. This is achieved using so-called Model Predictive Control which achieves the wanted behaviour by predicting how the platform will move based on its current state while implementing the constraints of the platform directly into the model. Since all of the parameters in the model are actual physical quantities, this makes the model easier to tune. A key component in this solution is the so-called tilt coordination which consists of substituting a lateral/longitudinal acceleration with the acceleration of gravity by tilting the driver. Constructing and implementing this model in Matlab we verify it by using data extracted from the simulator environment. We see that the parameters consisting of angles, rotational velocities and linear accelerations are tracked very well while respecting the constraints for the platform, constraints that can be easily changed to fit the current simulator.We also see that the model successfully implements tilt coordination into the behaviour of the platform. This model performs extraordinarily well in theory, what remains is to implement this to the motion platform and fine-tune it. / Oryx Simulations tillverkar simulatorer i huvudsak för gruv- och skogsindustrinvilket används i utbildnings- och marknadsföringssyfte. Simulatorerna använder en röorelseplattform för att spegla hur fordonet i simulatormiljön rör sig. Denna plattform lutar och accelererar föraren för att förstarka upplevelsen. Tidigare har ett så kallat klassiskt washout-filter använts för att kontrollera plattformen som lämnar en del i övrigt att onska vad gäller hur väl fordonets rörelser speglas, hur lätt det ar att justera samt hur det hanterar plattformens begränsningar. Detta projekt ämnar producera en modell som väl speglar vinklar,hastigheter och accelerationer samtidigt som den respekterar plattformens gränser. I tillägg till detta bör modellen vara enkel att modifiera och justera. Detta uppnås genom så kallad Model Predictive Control som förutsager hur plattformen kommer röra sig utifrån dess aktuella tillstånd samtidigt som den respekterar de tvång som finns på plattformen direkt i modellen. Då alla parametrar i modellen är faktiska fysiska kvantiteter blir modellen märkbart lättare att justera. En viktig komponent i denna lösning är så kallad tilt coordination vilket består i att substituera lateral/longtudinell acceleration med en komposant av tyngdaccelerationen genom att luta föraren. Denna modell konstrueras och implementeras i Matlab och verifieras genom att använda extraherat data från den simulerade miljön. Vi kan se att parametrarna som består av vinklar, rotationella hastigheter och linjära accelerationer speglas väldigt väl, samtidigt som tvången på plattformen respekteras. Dessa tvång kan enkelt modieras for att passa den aktuella simulatorn. Vi ser även att modellen framgångsrikt implementerar tilt coordination i plattformens beteende. I teorin har denna modell väldigt bra prestanda; vad som kvarstår är att implementera den på en rörelseplattform och finjustera modellen.