Background: This study examined whether levels of parental reflective function (RF), parental expressed emotion (EE) and children’s attachment styles are significantly related in a sample of children with high levels of conduct disorder (CD) symptoms. Method: The sample (n = 143) consisted of children aged 5-7 years at risk of behaviour problems. Participants were recruited from a borough of London and a unitary authority in the south west of England. Data for the three main variables and confounders were collected using semi-structured interview, direct observation and questionnaires from both parents and children. The Parent Development Interview (PDI) was used to assess RF; the Five-Minute Speech Sample to assess EE and the Manchester Child Attachment Story Task (MCAST) to assess child attachment. Results: Global levels of maternal RF did not significantly differ between the securely and insecurely attached groups of children. Mothers of securely attached children, however, had higher RF ratings on the negative interactions and anger subscales of the PDI compared to mothers of insecurely attached children. No significant difference was found in parental EE between secure and insecurely attached children. High EE-warmth was associated with high global RF, but there was no significant relationship between EE-criticism and RF. Multiple logistic regression found no significant relationships between parental RF, parental EE and child attachment. Conclusions: These findings may suggest that attachment classification influences the levels of maternal RF in specific negative situations. Conversely it is possible that high maternal RF in such situations enables mothers to respond more sensitively to their child, leading to more secure attachment. The finding that maternal RF and EE were not associated with child attachment may suggest these variables are not strongly related, the sample is too small to detect any effect or that the specific sample lacks variability in scores. To the author’s knowledge this is the first study to test for these relationships with confounders included in the model, which may explain the null findings.

In recent years there has been an explosion in the rates of obesity, defined as a body mass index greater than 30kg/ m2, and associated cardiovascular disease. Alterations in peripheral glucocorticoid metabolism have been suggested to play a role in the development of obesity. Obesity occurs in both sexes, but the risk of associated metabolic disturbance and vascular dysfunction is greater in men. Although there is no accepted definition of obesity in rodents, the term is used to describe animals with a significant increase in fat pad mass often achieved by feeding a high fat diet. Although animal models of obesity have been useful in delineating potential mechanisms linking obesity with its metabolic and vascular sequelae, most studies have been in male animals and, thus, have not addressed sex differences. Additionally, emerging evidence shows that obesity during pregnancy is associated with increased cardio-metabolic and vascular disease in offspring, although the processes underlying such ‘programming’ effects are unclear. This thesis addresses the hypothesis that exposure to postnatal, or maternal obesity will alter both metabolism and vascular function in mice. Male and female mice maintained on a high fat and sugar diet from 5 weeks of age had increased adipose tissue deposition in adulthood. However there were striking sex differences in glucose homeostasis, mRNA levels and glucocorticoid metabolism, with males being more severely affected. Treatment of male mice with 17β-estradiol ameliorated a number of the effects of the high fat diet, including weight gain and altered glucose homeostasis; additionally estradiol altered glucocorticoid metabolism in the adipose so that it resembled that of females. Suprisingly, given the changes in metabolism, obesity in adult mice produced only small changes in vascular function and did not alter vascular remodelling following injury. The effects of maternal obesity were studied using male offspring aged 3 and 6 months. The offspring of obese mothers had similar body weight, adiposity, plasma lipid and plasma hormone concentrations to controls. In contrast, exposure to obesity in utero was associated with receptor specific changes in agonist-mediated contraction and decreased endothelium-dependent relaxation in male offspring. Despite these changes in vascular function, no alterations in blood pressure or vascular remodelling following injury were present. These results demonstrate that the more profound changes in glucose-insulin homeostasis associated with obesity in male humans can be recapitulated in rodent models and imply that estradiol plays a role in protecting the metabolism of female mice, potentially by alteration of glucocorticoid metabolism. Despite altered metabolism in postnatal obesity vascular function remained normal suggesting metabolic and vascular dysfunction are not intrinsically linked. Conversely, maternal obesity did not cause any overt changes in offspring metabolism but caused vascular dysfunction implying these parameters can be programmed independently.

Cachexia affects up to two thirds of all cancer patients with progressive disease. It is a syndrome characterised by weight-loss, anorexia, fatigue, asthenia, peripheral oedema, and is responsible for around 20% of cancer deaths. Cachectic patients suffer loss of both muscle mass and adipose tissue (with comparative sparing of visceral protein) and the lean tissue loss appears resistant to nutritional support. Progress in the treatment of cancer cachexia has been hampered due to poor understanding of the molecular mechanisms of skeletal muscle wasting in humans (rather than preclinical models) combined with a lack of accurate phenotyping particularly with respect to loss of skeletal muscle mass and function. The aim of the present thesis was to improve the knowledge and tools available for early intervention studies. The thesis focused on skeletal muscle as a key compartment in cancer cachexia. The experimental model was patients with upper gastrointestinal (UGI) cancer undergoing potentially curative surgery due to the associated higher incidence of cachexia along with the ability to access tissue biopsies. The thesis broadly divides into two sections. Part I reports a series of cancer cachexia biomarker discovery studies based on direct biopsy and analysis of human skeletal muscle. Part II focused on assessment and phenotyping of skeletal muscle mass and function in cachectic UGI cancer patients. In addition, the feasibility of longitudinal clinical studies that utilise such methodology is reported. Intramuscular β-dystroglycan protein content (assessed using Western blot) was identified as a potential biomarker of cancer cachexia whereas changes in the structural elements of muscle (myosin heavy chain or dystrophin) appeared to be survival biomarkers. Using transcriptomics, an 82-gene signature was demonstrated to correlate with weight-loss. Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to examine the genes from this signature that were most upregulated. The exercise activated genes, CAMk2β and TIE1, correlated positively with weight-loss across different muscle groups (Rectus abdominis, Vastus lateralis, Diaphragma) indicating that cachexia was not simply due to inactivity and suggesting that these genes could be used as biomarkers of cachexia. None of the biomarkers discovered were consistent with pre-clinical models and therefore require further study before progressing to a validation programme. Electron microscopy of muscle biopsies demonstrated that the number and size of intramyocellular lipid droplets was increased in the presence of cancer and increases further with weightloss/ loss of adipose mass in other body compartments. The specific mechanisms and drivers of this phenomenon remain to be elucidated, but could relate to enhanced lipolysis or mitochondrial dysfunction in skeletal muscle as well as influencing muscle mechanical quality. Physiological assessment of patients with cancer cachexia established the negative impact that cachexia can have on muscle mass, function, muscle quality and quality of life, but demonstrated that the degree of impairment varies with sex and between muscle groups. Furthermore, the challenge of longitudinal studies in this patient group where frailty and clinical deterioration limit repeated assessments was highlighted. Such issues emphasise the need for a dual approach to the classification of cancer cachexia: if molecular markers prove difficult to discover or validate, then more specific and robust physiological indices of skeletal muscle mass and function may be the more important route to improve clinical trial design and cachexia classification.

Pre-eclampsia is a pregnancy-related disorder characterised by high blood pressure, proteinuria and oedema. The aetiology of the disease is unclear but evidence suggests that endothelial dysfunction is central to the development of the maternal syndrome. Kinins are endogenous peptides released by the endothelium that contribute to the regulation of cardiovascular homeostasis by inducing vasodilation, fibrinolysis and angiogenesis. Given that pre-eclampsia is associated with reduced endotheliumdependent relaxation, coagulation abnormalities and an angiogenic imbalance, it was hypothesised that alterations of kinin receptor-mediated responses may be involved in the pathogenesis of the condition. To investigate whether changes in kinin receptor activity are involved in the impairment of endothelium-dependent relaxation observed in pre-eclampsia, the effects of specific B2 and B1 receptor agonists and antagonists on myometrial vascular tone were tested on arteries from healthy pregnancy and pre-eclampsia. The results demonstrated that in addition to classical bradykinin B2 receptor-mediated relaxation, a subset of healthy patients exhibited nitric oxide-dependent relaxation to the B1 receptor agonist Lys-des- Arg9-BK (LDABK) which could not be inhibited by either B1 or B2 receptor antagonists. Also, vessels that exhibited this novel response to LDABK were more sensitive to bradykinin. Furthermore, this study revealed that patients with pre-eclampsia had an attenuated response to both bradykinin and LDABK. Immunolocalisation and mRNA expression of the kinin receptors in the myometrium revealed no differences between healthy pregnancy and pre-eclampsia suggesting that disturbances of kinin receptor signalling rather than changes in receptor distribution or expression levels may be involved in the reduction of kinin-mediated responses in these patients. The role of kinins in mediating placental angiogenesis in healthy pregnancy and preeclampsia was determined using the endothelial tube formation assay in primary human umbilical vein endothelial cells (HUVECs) isolated from healthy women and women with pre-eclampsia. B2 and B1 receptor agonists induced endothelial tube formation via a VEGF-dependent, nitric oxide-independent mechanism in healthy HUVECs cultured in normoxic conditions. HUVECs isolated from women with pre-eclampsia cultured under normoxia and HUVECs from healthy pregnancies cultured under hypoxia exhibited greater levels of angiogenic branching compared with healthy normoxic cells, but were unresponsive to bradykinin and LDABK. Incubation of these cells with a VEGF receptor inhibitor reduced the elevated levels of tube formation indicating that this effect may be due to hypoxic upregulation of VEGF or an intrinsic difference in their angiogenic capacity. Further studies are required to determine the cause for the differences in angiogenic potential between healthy and pre-eclamptic cells and the impact this could have on placental vascular development and the pathogenesis of preeclampsia.

Effects of sulfadiazine, sulfathiazole, and sulfapyridine on the thyroid gland and blood pressure were investigated in the rat. Thiouracil, a known potent anti-thyroid substance, was employed as a standard with which the drugs were compared. Four groups of young male albino rats were injected with graded doses of thiouracil, sulfadiazine, sulfathiazole, and sulfapyridine, suspended in distilled water, over a '6-dsy period, respectively. A 0.027' solution of the drug was incorporated into the drinking water daily. A control group was injected with physiological saline and a 0.02" solution of the saline solution was incorporated into the drinking water. Thiouracil and the sulfenamiaes acted as anti-thyroid agents. Goiterous conditions developed, including thyroid hypertrophy, reduced food intake, as well as an increase in body weight concomitantly with reduced oxygen consumption and reduction in the level of iodinated compounds in the blood. A slight increase in the systolic blood pressure was also noted. Results were obtained by means of spectrophotometry, oxygen consumption rates, blood pressure determinations, and gross analyses of the thyroid glands.

International Telemetering Conference Proceedings / November 04-07, 1991 / Riviera Hotel and Convention Center, Las Vegas, Nevada / Based on the theory of orthogonality, two orthogonal multiplex systems called frequency division multiplexing(FDM) and time division multiplexing(TDM) have long been developed. Therefore, many people tend to think that these two systems represent the ONLY two multiplexing methods that satisfy the orthogonal condition. However, after years of research, we've discovered a new kind of orthogonal functions called Bridge functions. The Bridge functions have the every promise of being the basis for constructing an entirely new kind of telemetry system, which has been named as sequency division multiplexing(SDM). Since the Bridge functions are the mathematical basis of the new telemetry system, we will give a summary of the Bridge functions at first. We have successfully constructed an experimental prototype called BAM-FM system in our laboratory. The main ideas, block diagram, operational principles, and technical problems are discussed in this paper. All our work has proved that SDM has not only research interests, but also practical value.

International Telemetering Conference Proceedings / November 04-07, 1991 / Riviera Hotel and Convention Center, Las Vegas, Nevada / Based on the theory of orthogonality, two orthogonal multiplex systems called frequency division multiplexing (FDM) and time division multiplexing (TDM) have long been developed. Therefore, many people tend to think that these two systems represent the ONLY two multiplexing methods that satisfy the orthogonal condition. However, after years of research, we've discovered a new kind of orthogonal functions called Bridge functions. The Bridge functions have the every promise of being the basis for constructing an entirely new kind of telemetry system, which has been named as sequency division multiplexing (SDM). Since the Bridge functions are the mathematical basis of the new telemetry system, we will give a summary of the Bridge functions at first. We have successfully constructed an experimental prototype called BAM-FM system in our laboratory. The main ideas, block diagram, operational principles, and technical problems are discussed in this paper. All our work has proved that SDM has not only research interests, but also practical value.

As oil and gas supply decrease, it becomes more important to quantify the uncertainty associated with reservoir models and implementation of field development decisions. Various geostatistical methods have assisted in the development of field scale models of reservoir heterogeneity. Sequential simulation algorithms in geostatistic require an assessment of local uncertainty in an attribute value at a location followed by random sampling from the uncertainty distribution to retrieve the simulation value. Instead of random sampling of an outcome from the uncertainty distrubution, the retrieval of an optimal simulated value at each location by considering an economic loss function is demonstrated in this thesis. By applying a loss function that depicts the economic impact of an over or underestimation at a location and retrieving the optimal simulated value that minimizes the expected loss, a map of simulated values can be generated that accounts for the impact of permeability as it relates to economic loss. Both an asymmetric linear loss function and a parabolic loss function models are investigated. The end result of this procedure will be a reservoir realization that exhibits the correct spatial characteristics (i.e. variogram reproduction) while, at the same time, exhibiting the minimum expected loss in terms of the parameters used to construct the loss function. The process detailed in this thesis provides an effective alternative whereby realizations in the middle of the uncertainty distribution can be directly retrieved by application of suitable loss functions. An extension of this method is to alter the loss function (so as to emphasize either under or over estimation), other realizations at the extremes of the global uncertainty distribution can also be retrieved, thereby eliminating the necessity for the generation of a large suite of realizations to locate the global extremes of the uncertainty distribution. / text

The assessment of rehabilitation effectiveness in the post-stroke hemiparetic population has primarily focused on walking speed. Walking speed, however, may be improved through a number of mechanisms; increased speed can be achieved through a combination of increased propulsion (propelling the center of mass forward) and swing initiation (resulting in longer and faster steps) in either the paretic or nonparetic leg. Therefore the objective of this study was to use a detailed musculoskeletal model and forward dynamics simulations to identify the individual muscle contributions to forward propulsion and swing initiation following locomotor training in two post-stroke hemiparetic patients who had similar speed increases following training, one utilizing an “ankle strategy” (increases in ankle power generation to accelerate the trunk forward) and one a “hip strategy” (increases in hip flexor generation of the swing leg to accelerate the leg forward) to increase speed. Each subject participated in locomotor therapy training using a body weight supported treadmill modality. Strategy classification was based on inverse dynamics analysis pre- and post-training. The simulation analyses revealed that forward propulsion was achieved primarily through the uniarticular plantarflexors and the contralateral knee extensors in both subjects. The main difference between the two strategies occurred primarily in the hip muscle contributions to swing initiation. The “hip strategy” subject, in addition to using the hip flexors to accelerate the leg forward, had higher contributions from the contralateral non-sagittal plane hip muscles to generate energy to the leg to initiate swing. These results suggest that using either the “ankle strategy” or the “hip strategy” to increase speed post-training results in similar muscle function post-training walking with differences primarily occurring in the hip muscle contributions to swing initiation. Future studies analyzing both pre- and post-training may reveal changes in muscle function that correspond more with the strategy classifications. / text

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