Background: Rheumatoid arthritis (RA) is characterised by excessive production of tumour necrosis factor alpha (TNFα). This leads to rheumatoid cachexia, a condition characterised by increased resting energy expenditure (REE) and loss of fat-free mass (FFM) leading to functional disability, decreased strength and balance. The aims of this research work was to: a) to develop a new REE equation in order to continuously monitor abnormal changes in REE in the RA population, b) to investigate if smoking further enhances hypermetabolism and c) to examine if the new anti-TNFα medication reverses this metabolic abnormality. Methods: 68 patients with RA were assessed for demographic and anthropometrical characteristics, REE (indirect calorimetry), body composition (bioelectrical impedance), and disease activity [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), disease activity score 28 (DAS28) and health assessment questionnaire (HAQ)]. 20 of the total 68 patients, about to start anti-TNFα therapy, underwent the exact same aforementioned procedures but on three separate occasions (Baseline: two weeks prior to anti-TNFα treatment, Time-1 and Time-2: two weeks and three months, respectively, after the drug had been introduced. Results: Study 1: Based on FFM and CRP, a new equation was developed which had a prediction power of R2=0.76. The new equation revealed an almost identical mean with measured REE (1645.2±315.2 and 1645.5±363.1 kcal/day, p>0.05), and a correlation coefficient of r=0.87 (p=0.001). Study 2: Smokers with RA demonstrated significantly higher REE (1513.9±263.3 vs. 1718.1±209.2 kcal/day; p=0.000) and worse HAQ (1.0±0.8 vs. 1.7±0.8; p=0.01) compared to age and FFM matched RA non-smokers. The REE difference was significantly predicted by the interaction smoking/gender (p=0.04). Study 3: Significant increases were observed in REE (p=0.002), physical activity (p=0.001) and protein intake (p=0.001) between the three times of assessment. Moreover, disease activity significantly reduced [ESR (p=0.002), DAS28 (p=0.000), HAQ (p=0.000) and TNFα (p=0.024)] while FFM and total body fat did not change (both at p>0.05). Physical activity and protein intake were found to be significant within-subject factors for the observed REE elevation after 12-weeks on anti-TNFα treatment (p=0.001 and p=0.024, respectively). Conclusions: Findings from the first study revealed that the newly developed REE equation provides an accurate prediction of REE in RA patients. Moreover, the results from the second study showed that cigarette smoking further increases REE in patients with RA and has a negative impact on patients’ self-reported functional status. Finally, our data from the third study suggest that REE remains elevated not because of the maintenance of the RA-related hypermetabolism but due to the concomitant significant increases in physical activity and protein intake.

Made available in DSpace on 2014-12-17T14:13:19Z (GMT). No. of bitstreams: 1 FernandoPB.pdf: 4835339 bytes, checksum: 31251ef256da75068c94b80cfee05d1f (MD5) Previous issue date: 2007-12-03 / The relation between metabolic demand and maximal oxygen consumption during exercise have been investigated in different areas of knowledge. In the health field, the determination of maximal oxygen consumption (VO2max) is considered a method to classify the level of physical fitness or the risk of cardiocirculatory diseases. The accuracy to obtain data provides a better evaluation of functional responses and allows a reduction in the error margin at the moment of risk classification, as well as, at the moment of determination of aerobic exercise work load. In Brasil, the use of respirometry associated to ergometric test became an opition in the cardiorespiratory evaluation. This equipment allows predictions concerning the oxyredutase process, making it possible to identify physiological responses to physical effort as the respiratory threshold. This thesis focused in the development of mathematical models developed by multiple regression validated by the stepwise method, aiming to predict the VO2max based on respiratory responses to physical effort. The sample was composed of a ramdom sample of 181 healthy individuals, men and women, that were randomized to two groups: regression group and cross validation group (GV). The voluntiars were submitted to a incremental treadmill test; objetiving to determinate of the second respiratory threshold (LVII) and the Peak VO2max. Using the m?todo forward addition method 11 models of VO2max prediction in trendmill were developded. No significative differences were found between the VO2max meansured and the predicted by models when they were compared using ANOVA One-Way and the Post Hoc test of Turkey. We concluded that the developed mathematical models allow a prediction of the VO2max of healthy young individuals based on the LVII / A rela??o entre a demanda metab?lica e o consumo de oxig?nio durante a pr?tica de exerc?cios f?sicos ? alvo de investiga??o em distintas ?reas do conhecimento. No campo da sa?de, a determina??o do consumo m?ximo de oxig?nio (VO2m?x) ? considerada um m?todo para classificar o n?vel de aptid?o f?sica ou risco de doen?as cardiocirculat?rias. A obten??o de dados de forma acurada possibilita uma melhor avalia??o das respostas funcionais, o que permite reduzir a margem de erros tanto no momento da classifica??o dos riscos, como tamb?m no momento da determina??o das cargas de treinamento aer?bico. No Brasil a utiliza??o da ventilometria conjugado ao teste de ergom?trico passou a ser uma op??o na avalia??o cardiorrespirat?ria. O emprego deste equipamento possibilita inferir sobre o processo de oxidorredutase, permitindo identificar respostas fisiol?gicas ao esfor?o como o limiar ventilat?rio. A presente tese centrou-se no desenvolvimento de modelos matem?ticos desenvolvidos por meio de regress?o m?ltipla com valida??o pelo m?todo stepwise com o objetivo de predi??o do VO2m?x tomando como base, as respostas ventilat?rias ao esfor?o. Para tanto, o estudo contou com uma amostra aleat?ria de 181 indiv?duos saud?veis, de ambos os sexos, que foram randomizados em dois grupos: grupo de regress?o e o grupo de valida??o cruzada (GV). Os volunt?rios foram submetidos a teste cardiopulmonar em esteira rolante em protocolo incremental; onde se visou a determina??o do limiar ventilat?rio II (LVII) e o VO2m?x de pico. Atrav?s da aplica??o do m?todo adi??o forward foram desenvolvidos 11 modelos de predi??o do VO2m?x em esteira rolante. N?o foram encontradas diferen?as significativa entre o VO2m?x mensurado com os preditos pelos modelos quando comparados pelo teste t pareado. Os resultados possibilitam-nos concluir que os modelos matem?ticos desenvolvidos permitem estimar o VO2m?x de indiv?duos jovens e h?gidos, tendo como ponto de refer?ncia o LVII

L'objectif de cette thèse vise à améliorer la définition des vibrations (« mouvement sismique ») sur des sites « durs » (sédiments raides ou rochers) liés à des scénarios (séismes de magnitude entre 5 et 6.5, distances inférieures à 50 kilomètres) représentatifs du contexte métropolitain français. Afin de contraindre ces mouvements sismiques sur sites « durs », une base de données accélérométriques a été construite, à partir des enregistrements accélérométriques japonais K-NET et KiK-net qui ont l'avantage d'être publiques, nombreux et de grande qualité. Un modèle de prédiction des mouvements sismiques (spectre de réponse en accélération) a été conçu à partir de cette nouvelle base. La comparaison entre modèles théoriques et observations montre la dépendance des vibrations sur sites rocheux à la fois aux caractéristiques de vitesse du site (paramètre classique décrivant la vitesse des ondes S dans les 30 derniers mètres) et aux mécanismes d'atténuation hautes fréquences (un phénomène très peu étudié jusque-là). Ces résultats confirment une corrélation entre ces deux mécanismes (les sites rocheux les plus mous atténuent plus le mouvement sismique à hautes fréquences) et nous proposons un modèle de prédiction du mouvement sismique prenant en compte l'ensemble des propriétés du site (atténuation et vitesse). Les méthodes nouvelles de dimensionnement dynamiques non linéaires (à la fois géotechniques et structurelles) ne se satisfont pas des spectres de réponse mais requièrent des traces temporelles. Dans le but de générer de telles traces temporelles, la méthode stochastique non stationnaire développée antérieurement par Pousse et al. 2006 a été revisitée. Cette méthode semi-empirique nécessite de définir au préalable les distributions des indicateurs clés du mouvement sismique. Nous avons ainsi développé des modèles de prédiction empiriques pour la durée de phase forte, l'intensité d'Arias et la fréquence centrale, paramètre décrivant la variation du contenu fréquentiel au cours du temps. Les nouveaux développements de la méthode stochastique permettent de reproduire des traces temporelles sur une large bande de fréquences (0.1-50 Hz), de reproduire la non stationnarité en temps et en fréquence et la variabilité naturelle des vibrations sismiques. Cette méthode présente l'avantage d'être simple, rapide d'exécution et de considérer les bases théoriques de la sismologie (source de Brune, une enveloppe temporelle réaliste, non stationnarité et variabilité du mouvement sismique). Dans les études de génie parasismique, un nombre réduit de traces temporelles est sélectionné, et nous analysons dans une dernière partie l'impact de cette sélection sur la conservation de la variabilité naturelle des mouvements sismiques. / The aim of this thesis is to improve the definition of vibrations ("seismic motion") on "hard" sites (hard soils or rocks) related to scenarios (earthquakes of magnitude between 5 and 6.5, distances less than 50 km) representative of the French metropolitan context.In order to constrain the seismic motions on "hard" sites, an accelerometric database was built, from the K-NET and KiK-net Japanese recordings which have the benefit of being public, numerous and high quality. A ground motion prediction equation for the acceleration response spectra was developed from this new database. The comparison between theoretical models and observations shows the dependence of vibration on rock sites in both the velocity characteristics of the site (classical parameter describing the S-wave velocity in the last 30 meters) and the high frequency attenuation mechanisms (a phenomenon little studied up to now). These results confirm a correlation between these two mechanisms (the high frequency seismic motion is more attenuated in the case of softer rock sites) and we propose a ground motion prediction equation taking into account all the properties of the site (attenuation and velocity).New methods of nonlinear dynamic analysis (both geotechnical and structural) are not satisfied with the response spectra but require time histories. To generate such time histories, the non-stationary stochastic method previously developed by Pousse et al. (2006) has been revisited. This semi-empirical method requires first to define the distributions of key indicators of seismic motion. We have developed empirical models for predicting the duration, the Arias intensity and the central frequency, parameter describing the frequency content variation over time. New developments of the stochastic method allow to reproduce time histories over a wide frequency band (0.1-50 Hz), to reproduce the non-stationarity in time and frequency and to reproduce the natural variability of seismic vibrations. This method has the advantage of being simple, fast and taking into account basic concepts of seismology (Brune's source, a realistic envelope function, non-stationarity and variability of seismic motion). In earthquake engineering studies, a small number of time histories is selected, and we analyze in the last part the impact of this selection on the conservation of the ground motion natural variability.

As flight flutter testing on an airplane progresses to high dynamic pressures and high Mach number region, it becomes very difficult for engineers to predict the level of the remaining stability in a flutter-prone mode and flutter-prone mechanism when response data is infested with uncertainty. Uncertainty and ensuing scatter in modal data trends always leads to diminished confidence amidst the possibility of sudden decrease in modal damping of a flutter-prone mode. Since the safety of the instrumented prototype and the crew cannot be compromised, a large number of test-points are planned, which eventually results in increased development time and associated costs. There has been a constant demand from the flight test community to improve understanding of the con-ventional methods and develop new methods that could enable ground-station engineers to make better decision with regard to flutter susceptibility of structural components on the airframe. An extensive literature survey has been done for many years to take due cognizance of the ground realities, historical developments, and the state of the art. Besides, discussion on the results of a survey carried on occurrences of flutter among general aviation airplanes has been provided at the very outset. Data for research comprises results of Computational Aero elasticity Analysis (CAA) and limited Flight Flutter Tests (FFTs) on two slightly different structural designs of the airframe of a supersonic fixed-wing airplane. Detail discussion has been provided with regard to the nature of the data, the certification requirements for an airplane to be flutter-free in the flight-envelope, and the adopted process of flight flutter testing. Four flutter-prone modes - with two modes forming a symmetric bending-pitching flutter mechanism and the other two forming an anti-symmetric bending-pitching mechanism have been identified based on the analysis of computational data. CAA and FFT raw data of these low frequency flutter modes have been provided followed by discussion on its quality and flutter susceptibility of the critical mechanisms. Certain flight-conditions, at constant altitude line and constant Mach number lines, have been chosen on the basis of availability of FFT data near the same flight conditions. Modal damping is often a highly non-linear function of airspeed and scatter in such trends of modal damping can be very misleading. Flutter margin (FM) parameter, a measure of the remaining stability in a binary flutter mechanism, exhibits smooth and gradual variation with dynamic pressure. First, this thesis brings out the established knowledge of the flutter margin method and marks the continuing knowledge-gaps, especially about the applicable form of the flutter margin prediction equation in transonic region. Further theoretical developments revealed that the coefficients of this equation are flight condition depended to a large extent and the equation should be only used in small ‘windows’ of the flight-envelope by making the real-time flutter susceptibility assessment ‘progressive’ in nature. Firstly, it is brought out that lift curve slope should not be treated as a constant while using the prediction equation at constant altitudes on an airplane capable of transonic flight. Secondly, it was realized that the effect of shift in aerodynamic canter must be considered as it causes a ‘transonic-hump’. Since the quadratic form of flutter margin prediction equation developed 47 years ago, does not provide a valid explanation in that region, a general equation has been derived. Furthermore, flight test data from only supersonic region must be used for making acceptable predictions in supersonic region. The ‘ameliorated’ flutter margin prediction equation too provides bad predictions in transonic region. This has been attributed to the non-validity of quasi-steady approximation of aerodynamic loads and other additional non-linear effects. Although the equation with effect of changing lift curve slope provides inconsistent predictions inside and near the region of transonic-hump, the errors have been acceptable in most cases. No consistent congruency was discovered to some earlier reports that FM trend is mostly parabolic in subsonic region and linear in supersonic region. It was also found that the large scatter in modal frequencies of the constituent modes can lead to scatter in flutter margin values which can render flutter margin method as ineffective as the polynomial fitting of modal damping ratios. If the modal parameters at a repeated test-point exhibit Gaussian spread, the distribution in FM is non-Gaussian but close to gamma-type. Fifteen uncertainty factors that cause scatter in modal data during FFT and factor that cause modelling error in a computational model have been enumerated. Since scatter in modal data is ineluctable, it was realized that a new predictive tool is needed in which the probable uncertainty can be incorporated proactively. Given the recent shortcomings of NASA’s flutter meter, the neural network based approach was recognized as the most suitable one. MLP neural network have been used successfully in such scenarios for function approximation through input-output mapping provided the domains of the two are remain finite. A neural network requires ample data for good learning and some relevant testing data for the evaluation of its performance. It was established that additional data can be generated by perturbing modal mass matrix in the computational model within a symmetric bound. Since FFT is essentially an experimental process, it was realized that such bound should be obtained from experimental data only, as the full effects of uncertainty factors manifest only during flight tests. The ‘validation FFT program’, a flight test procedure for establishing such bound from repeated tests at five diverse test-points in safe region has been devised after careful evaluation of guide-lines and international practice. A simple statistical methodology has been devised to calculate the bound-of-uncertainty when modal parameters from repeated tests show Gaussian distribution. Since no repeated tests were conducted on the applicable airframe, a hypothetical example with compatible data was considered to explain the procedure. Some key assumptions have been made and discussion regarding their plausibility has been provided. Since no updated computational model was made available, the next best option of causing random variation in nominal values of CAA data was exercised to generate additional data for arriving at the final form of neural network architecture and making predictions of damping ratios and FM values. The problem of progressive flutter susceptibility assessment was formulated such that the CAA data from four previous test-points were considered as input vectors and CAA data from the next test-point was the corresponding output. General heuristics for an optimal learning performance has been developed. Although, obtaining an optimal set of network parameters has been relatively easy, there was no single set of network parameters that would lead to consistently good predictions. Therefore some fine-tuning, of network parameters about the optimal set was often needed to achieve good generalization. It was found that data from the four already flown test-points tend to dominate network prediction and the availability of flight-test data from these previous test-points within the bound about nominal is absolutely important for good predictions. The performance improves when all the five test-points are closer. If above requirements were met, the predictive performance of neural network has been much more consistent in flutter margin values than in modal damping ratios. A new algorithm for training MLP network, called Particle Swarm Optimization (PSO) has also been tested. It was found that the gradient descent based algorithm is much more suitable than PSO in terms of training time, predictive performance, and real-time applicability. In summary, the main intellectual contributions of this thesis are as follows: • Realization of that the fact that secondary causes lead incidences of flutter on airplanes than primary causes. • Completion of theoretical understanding of data-based flutter margin method and flutter margin prediction equation for all ranges of flight Mach number, including the transonic region. • Vindication of the fact that including lift-curve slope in the flutter margin pre-diction equation leads to improved predictions of flutter margins in subsonic and supersonic regions and progressive flutter susceptibility assessment is the best way of reaping benefits of data-based methods. • Explanation of a plausible recommended process for evaluation of uncertainty in modal damping and flutter margin parameter. • Realization of the fact that a MLP neural network, which treats a flutter mechanism as a stochastic non-linear system, is a indeed a promising approach for real-time flutter susceptibility assessment.

There is an increase in the prevalence of obesity among people with schizophrenia thought to be due in part to the weight enhancing side-effects of medications commonly used to treat the symptoms of schizophrenia. Despite the deleterious health effects associated with obesity and its impact on quality of life and medication compliance, little is known about body composition and energy expenditure in this clinical group. The primary purpose of this thesis was to enhance understanding of body composition and energy expenditure, particularly resting energy expenditure in men with schizophrenia who take atypical antipsychotic medications. Unique to this investigation is the evaluation of clinical tools used to predict body composition and energy expenditure against reference methodologies in men with schizophrenia. Further, given the known links between obesity and physical activity, an additional but less comprehensive component of the thesis was a consideration of total and activity energy expenditure in addition to the interaction between psychiatric symptoms, side-effects of antipsychotic medications and physical activity also occurred as part of this thesis. Collectively, the goals of this thesis were addressed through a series of studies – the first two studies were related to the measurement and characteristics of body composition in men with schizophrenia, while the third and fourth studies were related to the measurement and characteristics of resting energy expenditure in men with schizophrenia. The fifth and sixth studies the utilised doubly labelled water technique to quantify activity and total energy expenditure in a small group of men with schizophrenia and explored the use of accelerometry in this cohort. The final study briefly considered the impact of psychiatric symptoms and self-reported medication side-effects on objectively measured physical activity. In the first study, thirty-one male adults previously diagnosed with schizophrenia and sixteen healthy male controls were recruited. Estimates of body composition derived from an anthropometry-based equation and from bioelectric impedance analysis (BIA) using deuterium dilution as the reference methodology to determine total body water were compared. The study also determined the validity of equations commonly used to predict body composition from BIA in the men with schizophrenia. A further aim was to determine the superiority of either BIA or body mass index (BMI) as an indicator of obesity in this cohort. The inclusion of the control group, closely matched for age, body size and body composition demonstrated that there was no difference in the ability of body composition prediction methods to distinguish between fat and fat-free mass (FFM) in controls and men with schizophrenia when both groups had similar body composition. However this study indicated that an anthropometry-based equation previously used in people with schizophrenia was a poor predictor of body composition in this cohort, as evidenced by wide limits of agreement (25%) and systematic variation of the bias. In comparison, the best predictor of percentage body fat (%BF) in this group was gained when impedance values were used to predict percentage body fat via the equation published by Lukaski et al (1986). Although percentage body fat was underpredicted using the Lukaski et al. (1986) equation, the mean magnitude was relatively small (1.3%), with the limits of agreement approximately 13%. Linear regression analysis revealed that %BF predicted using the Lukaski et al. (1986) equation explained 25% more of the variance in percentage body fat than BMI. Further, this study also indicated that BIA was more sensitive than BMI in distinguishing between overweight and obesity in this cohort of men with schizophrenia. Because of the almost exclusive use of BMI as an indicator of obesity in people with schizophrenia, the level of excess body fat may be in excess of that previously indicated. The second study extended the examination of body composition in men with schizophrenia. In this study, the thirty-one participants with schizophrenia (age, 34.2 ± 5.7 years; BMI, 30.2 ± 5.7 kg/m2) were individually matched with sedentary controls by age, weight and BMI. Deuterium dilution was used to distinguish between FFM and fat mass. The previous study had indicated that while BIA was a suitable group measure for obesity, on an individual level the technique lacked the precision required for investigating body composition in men with schizophrenia. Waist circumference was used as an indicator of body fat distribution. The findings of this study indicated that in comparison with healthy sedentary controls of similar body size and age, men with schizophrenia had higher levels of body fat which was more centrally distributed. Percentage body fat was on average 4% higher and waist circumference, on average 5 cm greater in men with schizophrenia than the sedentary controls of the same age and BMI. Further, this study indicates that the use of BMI to predict body fat in men with schizophrenia will result in greater bias than when it is used to predict body fat in other sedentary men. Commonly used regression equations to predict energy requirements at rest are based on the relationships between weight and resting energy expenditure (REE) and in such equations, weight acts as a surrogate measure of FFM. The objectives of study three were to measure REE in a small group of men with schizophrenia who were taking the antipsychotic medication clozapine and to determine whether REE can be predicted with sufficient accuracy to substitute for the measurement of REE in the clinical and/or research settings. Body composition was determined using deuterium dilution and REE was measured using a Deltatrac Metabolic Cart via a ventilated hood. The male participants, (aged 28.0 ± 6.7 yrs, BMI 29.8 ± 6.8 kg/m2) were weight stable at the time of the study and had been taking clozapine for 20.5 ± 12.8 months, with doses of 450 ± 140 mg/day. Of the six prediction equations evaluated, the equation of Mifflin et al. (1990) with no systematic bias, the lowest bias and the lowest limits of agreement proved to be the most suitable equation to predict REE in this cohort. The overestimation of REE can be corrected for by deducting 160 kcal/day from the predicted REE value when using the Mifflin et al. (1990) equations. However, the magnitude of the error associated with the prediction of REE for an individual is 370 kcal/day. The findings of this study indicate that REE cannot be predicted with sufficient individual accuracy in men with schizophrenia, therefore it was necessary to measure rather than predict REE in subsequent studies. In the fourth study, indirect calorimetry (Deltatrac Metabolic Cart via ventilated hood) and deuterium dilution were used to accurately determine REE, respiratory quotient (RQ) and FFM in 31 men with schizophrenia and healthy sedentary controls individually matched for age and BMI. Data from this study indicated that gross REE was lower in men with schizophrenia than in healthy sedentary controls of a similar age and body size. However, there was no difference between the groups in REE when REE was adjusted for FFM using the mathematically correct method (analysis of covariance with FFM as the covariate). There was however a statistically and clinically significant difference in resting, fasted RQ between men with schizophrenia and controls, suggesting that RQ rather than REE may be an important correlate worthy of further investigation in men with schizophrenia who take antipsychotic medications. Studies five and six involved the application of the doubly labelled water (DLW) technique to accurately determine total energy expenditure (TEE) and activity energy expenditure (AEE) in a small group of men with schizophrenia who had been taking the atypical antipsychotic medication clozapine. The participants were those who took part in study three. The purpose of these studies was to assess the validity of a commercially available tri-axial accelerometer (RT3) for predicting free-living AEE and to investigate TEE and AEE in men with schizophrenia. There was poor agreement between AEE measured using DLW and AEE predicted using the RT3. However, using the RT3 to measure inactivity explained over two-thirds of the variance in AEE. This study found that the relationship between current AEE per kilogram of body weight and change from baseline weight in men taking clozapine was strong although not significant. The sedentary nature of the group of participants in this study was reflected in physical activity levels, (PAL, 1.39 ± 0.27), AEE (435 ±352 kcal/day) and TEE (2511 ± 606 kcal/day) that fell well short of values recommended by WHO (2000) for optimal health and to prevent weight gain. Given the increasing recognition of the importance of sedentary behaviour to weight gain in the general community, further examination of the unique contributing factors such as medication side effects and symptoms of mental illness to activity levels in this clinical group is warranted. The final study used accelerometry (RT3) to objectively measure activity in a group of 31 men with schizophrenia who had been taking atypical antipsychotic medications for more than four months. The purpose of this study was to explore the relationships between psychiatric symptomatology, side-effects of medication and physical activity. Accelerometry output was analysed to provide a measure of inactivity and moderate intensity activity (MIA). The well-validated and reliable standardised clinical interview, the Positive and Negative Syndrome Scale (PANSS) was used as a measure of psychiatric symptoms. Perceived side-effects of medication were assessed using the Liverpool University Neuroleptic Rating Side-Effects Scale (LUNSER). Surprisingly, there was no relationship reported between any measures of negative symptoms and physical inactivity. However, self-reported measures of medication side-effects relating to fatigue, sleepiness during the day and extrapyramidal symptoms explained 40% of the variance in inactivity. This study found significant relationships between some negative symptoms and moderate intensity activity. Despite the expectation that as symptoms of mental illness reduce, inactivity may diminish and moderate intensity activity will increase, it may not be surprising that in practice this is an overly simplistic view. It may be that measures of social functioning and possibly therefore cognition may be better predictors of physical activity than psychiatric symptomatology per se.