This study creates and analyzes a model of the Hypothalamus-Pituitary-Adrenal axis to better understand cortisol rhythmicity perpetuated by circadian inputs, system dynamics and feedback inherent within the system. Differential equations are created to model human physiology with cortisol and precursor hormone outputs fit to physiologic data. The model is created with an input of circadian cues from the hypothalamus which are designed to create a more realistic stimulation of the cortisol cascade over predecessors. The study also incorporates additional signaling pathways unique to this model. The project explores the properties of the model under mathematical analysis; then, the simulation of known medical pathologies is used to analyze the model's predictive ability. It is found that incorporating the additional signaling pathway of Arginine Vasopressin increases the model's predictive capability in certain pathological conditions over predecessor models. Additionally, the origination of ultradian rhythm is explored through simulation and two possible explanations are found. First, pulsatile release of Adrenocorticotropic Hormone combined with negative feedback into the system from glucocorticoid receptors elicits the observed ultradian oscillations in humans. Additionally, simulations of increased hypothalamic monitoring and control of cortisol concentrations create a natural oscillation within the desired period. Results from numerical perturbation simulations and dynamic sensitivity analysis are employed to offer justification for known pathological conditions developing from circadian dysregulation. / Master of Science / This study aims to better understand the body's natural cortisol rhythm by creating a mathematical model of the Hypothalamus-Pituitary-Adrenal axis. The model uses differential equations to simulate human physiology and includes circadian cues from the suprachiasmatic nucleus to create a more accurate representation of how cortisol is released in the body. The study also incorporates additional signaling pathways and interactions unique to this model. By analyzing the model and simulating known medical conditions, it was found found that incorporating these additional signaling pathways improved the model's predictive ability in certain situations. Then, numerical simulations were used to investigate how circadian dysregulation can lead to pathological conditions.The study also explored the origin of ultradian rhythm, or short-term fluctuations in cortisol levels, and found two possible explanations. One explanation is the pulsatile release of Adrenocorticotropic Hormone combined with negative feedback from glucocorticoid receptors. Another explanation is increased hypothalamic control of cortisol concentrations. Overall, this study provides insights into the complex dynamics of the Hypothalamus-Pituitary-Adrenal axis and the origination of pathology in the system.

This group of experiments focused on relationships between diet, somatotropic axis, and growth. Growth hormone (GH) and insulin-like growth factor I (IGF-I) are factors in the somatotropic axis, and important to development of growth cartilage in the young animal. The entire study was divided into four main experiments. Characteristics of growth in 113 Thoroughbred foals born over a five year period were described with a series of empirical and physiological equations. Glycemic and insulinemic responses to different feed compositions were evaluated with glycemic response tests. The 24 hr pattern of plasma glucose, insulin, GH, and IGF-I was described in yearlings fed two meals a day. Finally, an association between ADG and IGF-I was described in Thoroughbreds from birth to 16 mo of age. Feeding diets to the foal that influence the somatotropic axis during growth may affect development of growth cartilage in unexpected or detrimental ways. The pattern of weight in Thoroughbred foals from birth to 16 mo of age was most closely described by multiple regression with a combination of age, girth, body length, and physeal circumference (R2 = 0.99). Glycemic and insulinemic responses were significantly higher in yearlings fed a sugar and starch supplement when compared to those fed a fat and fiber supplement (P = 0.043 and 0.031; respectively). Glucose and insulin secretion was significantly affected by the feeding of two meals in a 24 hr period (P < 0.0001). Plasma IGF-I was positively correlated with ADG from birth to 16 mo of age in foals fed either a fat and fiber or sugar and starch supplement (r = 0.34, P < 0.0001). The results from the series of experiments described here suggest a possible role of dietary mangement in reducing the risk of skeletal disorders that involve the influence of IGF-I on chondrocyte maturation. / Ph. D.

Opiate addiction is now a major public health problem. Pregnant women continue to use opiates during gestation; up to 5.4% of pregnant women report using illicit drugs during pregnancy. Previous studies have shown that perinatal insults and exposure to opiates such as morphine in utero can affect the development of the hypothalamic-pituitary-adrenal (HPA)-axis of the offspring and are associated with higher risk of developing neurobehavioral problems. Oxycodone, a semisynthetic putative kappa opioid receptor and partial mu opioid receptor agonist is now one of the most frequently abused pain killers during pregnancy, however limited data are available regarding whether and how perinatal oxycodone exposure (POE) alters the development and functions of the HPA-axis, the related stress axis and neurobehavioral outcomes of the offspring. Data from these experiments have provided novel evidence that POE indeed is associated with sex-specific changes in the HPA-axis in response to stress that persist beyond the neonatal period. 1) POE is associated with an increased adrenocorticotropic hormone (ACTH) response to corticotropin-releasing hormone (CRH), but not the corticosterone (CORT) response to CRH stimulation in late adolescent male offspring. 2) POE is associated with increased CORT, but not ACTH response to restraint stress test in adult female offspring. These changes in the HPA-axis response to stress may be partially explained by 1) an increase in the subpopulation of CRH neurons that also contain estrogen receptor-beta immunoreactivity following POE which then can exaggerate the stimulation of the HPA-axis, and 2) a decrease in mineralocorticoid receptor-mRNA expression in the hippocampus which may be associated with impaired negative feedback control of the HPA-axis by the limbic system. POE is also associated with cardiovascular changes in response to stress during a classical conditioning paradigm; adolescent male POE rats have a larger blood pressure increase than the control group. Although POE male rats can properly discriminate the stress versus non-stress cues in the conditioning paradigm, they do not retain this memory when retested during adulthood. When tested for learning and memory in a water maze, however, we did not find any differences between control rats and rats exposed to high dose oxycodone in utero. In addition, we demonstrated that exposure to the lower dose of oxycodone in utero is associated with hyperactivity in adult rats when tested in an open field. Our results make a significant contribution to the literature because they extend our knowledge about the effects of oxycodone on the developing brain and the resulting outcomes in animal models that are actually relevant to a current major public health problem in humans and will provide a platform for us to further study the underlying mechanisms and interventions that may mitigate these effects.

Two novel personal calibration procedures that do not require active user participation are presented. These procedures, in conjunction with a state-of-the-art remote eye-gaze tracking (REGT) technology, allow estimation of the angle between the optical and visual axes (angle kappa) automatically without explicit/active user involvement. The first algorithm for the binocular estimation of angle kappa (BEAK) is based on the assumption that at each time instant both eyes look at the same point on a surface with a known geometry (e.g., a computer monitor). The sensitivity of the BEAK procedure to the geometry of the observation surface and to the noise in the estimates of the optical axis is studied both analytically and in computer simulations. Experimental results with 4 adult subjects suggest that with the current REGT technology angle kappa can be estimated with an RMS error of 0.5°. The second personal calibration algorithm (‘calibrate and validate’, CaVa) adopts a probabilistic approach to the estimation of angle kappa in infants. Even though the presentation of visual stimuli at known positions is part of the procedure, the CaVa algorithm does not require/assume continuous fixation on the presented targets. If an infant attends to roughly half of the presented targets, angle kappa can be estimated accurately and with high confidence. In experiments with five babies, the average difference between repeated measurements of angle kappa was 0.04 ± 0.31°. The second part of the thesis describes two methods for automated measurement of eye misalignment in adults and infants. These methods are based on the user-calibration-free (UCF) technology presented in the first part of the thesis. The first method is based on the clinical Hirschberg test. It is shown that the UCF-REGT technology can improve significantly the accuracy of the Hirschberg test by enabling the estimation of subject-specific parameters (the Hirschberg ratio and angle kappa) in infants. The maximum error in the estimation of the horizontal and vertical components of eye misalignment in five orthotropic infants was shown to be less than 1°, which is significantly better than the accuracy of a standard clinical Hirschberg test. Finally, a novel Eye-Tracker Based Test (ETBT) for the estimation of the maximum (manifest + latent) angle of deviation is presented. ETBT is based on the UCF-REGT system. ETBT allows free head movements and does not require continuous fixation on specific targets. Experiments with 22 adult subjects demonstrated a good agreement of 0.7 ± 1.7° between ETBT and the gold-standard clinical procedure—the altenate prism and cover test. A pilot study with 5 orthotropic infants and one infant with strabismus demonstrated that the ETBT can be used in infants.

Two novel personal calibration procedures that do not require active user participation are presented. These procedures, in conjunction with a state-of-the-art remote eye-gaze tracking (REGT) technology, allow estimation of the angle between the optical and visual axes (angle kappa) automatically without explicit/active user involvement. The first algorithm for the binocular estimation of angle kappa (BEAK) is based on the assumption that at each time instant both eyes look at the same point on a surface with a known geometry (e.g., a computer monitor). The sensitivity of the BEAK procedure to the geometry of the observation surface and to the noise in the estimates of the optical axis is studied both analytically and in computer simulations. Experimental results with 4 adult subjects suggest that with the current REGT technology angle kappa can be estimated with an RMS error of 0.5°. The second personal calibration algorithm (‘calibrate and validate’, CaVa) adopts a probabilistic approach to the estimation of angle kappa in infants. Even though the presentation of visual stimuli at known positions is part of the procedure, the CaVa algorithm does not require/assume continuous fixation on the presented targets. If an infant attends to roughly half of the presented targets, angle kappa can be estimated accurately and with high confidence. In experiments with five babies, the average difference between repeated measurements of angle kappa was 0.04 ± 0.31°. The second part of the thesis describes two methods for automated measurement of eye misalignment in adults and infants. These methods are based on the user-calibration-free (UCF) technology presented in the first part of the thesis. The first method is based on the clinical Hirschberg test. It is shown that the UCF-REGT technology can improve significantly the accuracy of the Hirschberg test by enabling the estimation of subject-specific parameters (the Hirschberg ratio and angle kappa) in infants. The maximum error in the estimation of the horizontal and vertical components of eye misalignment in five orthotropic infants was shown to be less than 1°, which is significantly better than the accuracy of a standard clinical Hirschberg test. Finally, a novel Eye-Tracker Based Test (ETBT) for the estimation of the maximum (manifest + latent) angle of deviation is presented. ETBT is based on the UCF-REGT system. ETBT allows free head movements and does not require continuous fixation on specific targets. Experiments with 22 adult subjects demonstrated a good agreement of 0.7 ± 1.7° between ETBT and the gold-standard clinical procedure—the altenate prism and cover test. A pilot study with 5 orthotropic infants and one infant with strabismus demonstrated that the ETBT can be used in infants.

Following social defeat, male hamsters exhibit behavioral changes characterized by a breakdown of normal territorial aggression and an increase in submissive/defensive behaviors in the presence of a non-aggressive intruder (NAI). We have termed this phenomenon conditioned defeat (CD). By contrast, only a small subset of defeated females exhibit submissive/defensive behavior in the presence of a NAI. We hypothesized that fluctuations in gonadal hormones might contribute to differences in the display of submissive behavior in intact female hamsters. Following social defeat, proestrous females (higher endogenous estradiol) were more likely to display conditioned defeat compared with diestrous 1 (lower endogenous estradiol) females. This finding suggests that there is an estrous cycle-dependent fluctuation in the display of CD in female hamsters and suggests that increased estradiol might contribute to increased submissive behavior. We then demonstrated that ovariectomized females given estradiol prior to CD testing exhibited significantly higher submissive behavior in the presence of a NAI suggesting that estradiol increases the expression of CD in female hamsters. We have also shown that castrated males that were singly housed for four weeks displayed significantly more submissive behavior than did their intact counterparts. Interestingly, castrated and intact males that were singly housed for 10 days prior to behavioral testing displayed similar behavior during CD testing. Together these data suggest that androgens and isolation modulate the display of CD in male hamsters. Finally, we examined brain activation following CD testing in defeated males and females (in diestrus 1 and proestrus). Defeated male and proestrous females exhibited increased Fos activation in the dorsal lateral septum and hypothalamic paraventricular nucleus relative to defeated diestrous 1 females. Diestrous 1 females exhibited increased Fos expression in the lateral bed nucleus of the stria terminalis compared with both defeated groups. Collectively, these data suggest that gonadal hormones and duration of individual housing modulate the display of CD in female and male hamsters and that those animals which display CD exhibit differences in patterns of neuronal activation than do those that do not display CD.

Mental illness is common, and usually starts early in life. However, the majority of those affected never seek mental health care. The overall aim of this thesis was to increase knowledge about help-seeking young adults with mental illness in order to improve diagnostic procedures in clinical psychiatry. A group of young adult psychiatric out-patients (n=217) were consecutively invited to participate in the study between October 2002 and September 2003. Altogether 200 (92%) agreed to participate. Among them, there were 161 (80%) women and 39 (20%) men. Participants’ mean age was 22.4±1.9 years. All participants were carefully and comprehensively assessed with respect to axes I, II, IV and V in the DSM-IV. Psychiatric disorders and personality disorders were assessed using the Structured Clinical Interview for DSM-IV for axis I disorders and the Structured Clinical Interview for DSM-IV for axis II disorders. Psychosocial and environmental problems (axis IV) were evaluated through structured interviewing by a social worker and by self-assessment with a questionnaire. Professional and patient ratings on the Global Assessment of Functioning scale were compared before and after treatment. Patients also reported on the Swedish universities Scales of Personality, the Child and Adolescent Psychiatric Screening Inventory-Retrospect and the Coddington’s life event scale. Taken together, the young adult, psychiatric outpatients were characterized by an early onset of their mental disorders, by co-morbidity, by being female and by having mood or anxiety disorders. There were no significant differences between self-referred and those referred by medical professionals according to either number of current or lifetime diagnoses. Childhood onset of depression was associated with more severe symptoms, more psychosocial risk factors, and more childhood developmental delays. Axis IV psychosocial stress categories were related to the presence of axis I disorders, personality disorders, co-morbidity, and impaired functioning. Agreement between patients’ and professionals’ ratings on the GAF scale was good before treatment and excellent after treatment. In summary, the findings suggest that direct self-referral to specialized psychiatric care does not seem to be associated with overutilization of such care. Childhood onset of depression is associated with a more complex illness. The revised axis IV according to DSM-IV seems to have concurrent validity, but is still hampered by limited reliability. And finally, the results support the usefulness of the self-report GAF instrument for measuring outcome in psychiatric care.

This thesis deals with construction, connection and control axis with linear motor. The beginning of thesis is focused on principle of functioning and characteristics of linear motors. The following part describes used components of axis, their mechanical configuration and electrical wiring. Further thesis deals with creating PLC program and user interface for control axis in TwinCAT system. In last part is dealing correct software settings of axis.

Volvo Group Trucks Operation är ett världsledande företag inom lastbilsindustrin. På Volvofabriken i Skövde tillverkas motorerna till bland annat lastbilar och bussar. Syftet med detta examensarbete var att undersöka möjligheten till kameraövervakning i processen för att förenkla avvikelsehanteringen samt att ta fram en teknisk lösning till detta. Det finns många fördelar med kameraövervakning i processerna, bland annat att kunna se vad som händer inne i maskinerna och genom detta ha möjlighet att analyserna cykeltider och få bättre kännedom om processen. För att få reda på i vilket utsträckning kameraövervakning i processerna är tillåtet hölls ett möte med en förhandlingsledare för fackförbundet If metall. Resultatet av mötet var positivt, det krävs en MBL-förhandling för att dokumentera syftet, som inte får vara att övervaka medarbetarna. Genom intervjuer kunde det fastställas vad medarbetare krävde av systemet och för att få en bild över vad det finns för kameralösningar på marknaden gjordes studiebesök och benchmarking. En lösning kunde sedan väljas ut och valet landade på mjukvara och hårdvara från kameraföretaget Axis. Slutsatserna av examensarbetet är att kameraövervakning i bearbetningsprocesser skulle bidra till fler utredda avvikelser i maskinparken, en stabilare process och ett säkrare logistikflöde världen över. / Volvo Group Trucks Operation is a world-leading company in the trucking industry. The engines for trucks and buses, among other things, are manufactured at the Volvo factory in Skövde. The purpose of this thesis was to investigate the possibility of implementing camera monitoringin the process to simplify deviation management and develop a technical solution for it. There are advantages to camera monitoring in the processes, such as being able to see what is happening inside the machines and, through this, being able to analyse cycle times and gain a better understanding of the process. To determine the extent to which camera monitoring in the processes is allowed, a meeting was held with a negotiation leader from the labor union If Metall. The result of the meeting was positive, and it was determined that an agreement under the Co-Determination Act (MBL) is required to document the purpose, which should not be to monitor the employees. Through interviews, the requirements of the employees for the system were established, and to gain an overview of the camera solutions available on the market, site visits and benchmarking were conducted. A solution was then chosen, and the selection landed on software and hardware from the camera company Axis. The conclusion of the thesis is that camera monitoring in the machining processes would contribute to a higher number of investigated deviations in the machine park, a more stable process, and a safer logistics flow worldwide.

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