Thesis (M. Med. Sc.)--University of Queensland, 2001. / Includes bibliographical references.

Thesis (Ph. D.)--University of Texas at Austin, 2001. / Vita. Includes bibliographical references (leaves 197-202). Available also in a digital version from Dissertation Abstracts.

The main aim of this thesis was to improve our understanding of the development of early inhibitory emotions and emotion regulation from infancy, and the role of these emotions in early risk pathways. More specifically, this thesis investigated (1) the development of fearful temperament, its stability over the first 3 years of life, and its associations with later developing effortful control (EC) and guilt; (2) risk factors in infancy that predict later externalising psychopathology; and (3) the development of EC, and its associations with fear and guilt. Psychophysiological and observational measures were used, when available, to examine these emotional systems as well as their role in predicting later psychopathology. The thesis consists of 3 empirical chapters, investigating a sample of 70 typically developing children in a longitudinal, prospective manner. Behavioural fear was stable over time, but physiological fear peaked in year 2. Fearful infants continued to be fearful toddlers, and fear in infancy predicted fearfulness 2 years later. Fear and guilt were associated, and we showed for the first time that infant fear is a predictor of later developing guilt. EC increased from year 2 to year 3, showed inter-individual stability across time, and girls’ ability for EC surpassed the ability in boys. EC and guilt were not associated; however, EC and fear were associated in year 3, suggesting that early fear does not regulate later EC. This thesis identified two biomarkers in infancy for later psychopathology. A subgroup of toddlers with internalising problems displayed higher heart rate in infancy, whereas skin conductance arousal in infancy predicted aggressive behaviour in toddlers.

Despite current improvement in newborn care, infection is still a common cause of neonatal morbidity and mortality. Innate immunity is the first line of defence against pathogens particularly in newborn infants. Quantitative and functional deficit in non-cellular (complement system) and cellular (neutrophils) arms of innate immune system is believed to contribute to neonatal susceptibility to infection. Neutrophil granule subsets contain a variety of proteases, including elastase, cathepsins, MMP-9 and proteinase 3 along with different granule markers and receptors. This thesis demonstrated that normal term neonatal neutrophils express more proteinase 3 and CD177 on their surface while no differences were found in expression of markers CD35, CD66b and CD63 (representing the secretory, secondary and primary granule subsets, respectively). Cord neutrophils contain more PR3 than adult cells but the proportion of PR3 released by cord and adult neutrophils was similar. In contrast, neonatal neutrophils contained only half of the cathepsin G and elastase functional activity of adult neutrophils. Bronchoalveolar lavage fluid studied from preterm infants ventilated for respiratory distress demonstrated higher proteinase 3 concentrations in lavage samples from infants who went on to develop chronic lung disease than in infants with resolved respiratory distress syndrome. Concentration of proteinase 3 in lavage samples was significantly higher than MMP-9 and elastase levels, suggesting that it may have an important role in disease pathogenesis. Complement is an equally important component of the innate immune system that plays a central role in recruiting and activating neutrophils, as well as being directly bactericidal through the terminal lytic pathway. Analysis of neonatal complement system revealed that Complement function and terminal components levels particularly C9 are deficient (except C7) in healthy term newborn infants compared to normal adults. Bactericidal capacity of a selection of neonatal sera was tested along with adult sera against four serovars of Ureaplasma parvum, a potentially important perinatal pathogen. Results showed impaired bactericidal capacity of neonatal serum compared to adult serum especially against SV1. Ureaplasma SV3 was the most serum sensitive serovar whereas killing of the resistant serovars SV6 and 14 could not be induced by supplementation of the deficient components C6, C8 and C9.

No description available.

This thesis analyses transformations in pediatrics during its history as an organized medical specialty. Pediatricians emerged in a period of high infant and child mortality and poor public health to fight disease and treat difficult feeding problems. After mortality rates began to decline they turned to prevention, supervising the normal growth and development of healthy children. However, as prevention absorbed an ever larger proportion of their time, they became bored and dissatisfied. During the 1970s, competing groups of child health care providers such as pediatric nurse practitioners and family practitioners exacerbated pediatricians' difficulties. Worried about their possible disappearance as primary care specialists, pediatricians sought a new mission in ministering to children's non-physical problems. The "new pediatrics" focuses on the behavioral and psychosocial problems of children and adolescents. This study contributes to understanding how professions respond to changes and threats in their environment.

The neonatal period represents a critical time period in the development of the immune system. Adaptive human immune responses are generally viewed as immature at birth. However little is known about innate immune capacity at birth. The TLR system plays an integral role as pattern recognition receptors in the innate immune response. It is also critical in initiating and regulating the adaptive immune response. Preterm birth is associated with increased risk of developing infections in early life and has been associated with increased risk of development of other chronic disorders in later life; however the underlying mechanisms are not at all well understood. Recently, late preterm neonates (34-36 weeks gestation vs full term, 37+ weeks) have been identified as having significantly greater risks of morbidity and mortality in the perinatal period than their full term counterparts. Hence, we focus on examination of TLR responses in late preterm and full term neonates to better understand immune potential and function in these populations. We examined cord blood cytokine and chemokine responses following stimulation with a broad range of TLR agonists. Our results show for the first time that late preterm neonates have reduced capacity to produce both pro- and anti-inflammatory cytokines following stimulation with a panel of TLR agonists. This reduced responsiveness was not due to a reduction in the number of responding cells, but instead appears to be mediated by a reduction in the intrinsic levels of expression of TLRs and associated adaptor proteins. Because little is known about how the innate immune system develops throughout life, we next compared TLR responses in full term neonates to 7 children, adolescents and adults. We found that neonates had selective impairments in TLR responses, most notably in anti-inflammatory cytokine production and anti-viral immune responses compared to the other age groups. Epigenetic modifications, such as the addition or removal of acetyl groups to histone proteins by histone acetyl transferase (HAT) and histone deactylase (HDAC) respectively, are able to modify the expression of genes. Hence, environmental stimuli have been shown to influence gene expression in part by modifying the level or activity of these epigenetic regulators. Currently there are no studies which have examined how epigenetic modifications may influence neonatal innate immune responses. Hence, we sought to determine how modulation of endogenous HDAC activity would affect neonatal innate immune responses. We found that inhibition of HDAC had both inhibitory and enhancing effects on cytokine expression depending on the TLR pathway activated, indicating that the endogenous HDAC expression does not have a global inhibitory impact on all TLR-dependent responses. In summary, this body of work demonstrates that neonatal innate immune responses vary depending on gestational age, indicating that the final few weeks of gestation are crucial for maturation of responses to both bacteria and viruses. Neonates respond differently to TLR stimuli than do older individuals, further highlighting a maturation process of the innate immune system which continues throughout life. Finally, we have shown that environmental exposures may have powerful effects on immune responses in early life.

The neonatal period represents a critical time period in the development of the immune system. Adaptive human immune responses are generally viewed as immature at birth. However little is known about innate immune capacity at birth. The TLR system plays an integral role as pattern recognition receptors in the innate immune response. It is also critical in initiating and regulating the adaptive immune response. Preterm birth is associated with increased risk of developing infections in early life and has been associated with increased risk of development of other chronic disorders in later life; however the underlying mechanisms are not at all well understood. Recently, late preterm neonates (34-36 weeks gestation vs full term, 37+ weeks) have been identified as having significantly greater risks of morbidity and mortality in the perinatal period than their full term counterparts. Hence, we focus on examination of TLR responses in late preterm and full term neonates to better understand immune potential and function in these populations. We examined cord blood cytokine and chemokine responses following stimulation with a broad range of TLR agonists. Our results show for the first time that late preterm neonates have reduced capacity to produce both pro- and anti-inflammatory cytokines following stimulation with a panel of TLR agonists. This reduced responsiveness was not due to a reduction in the number of responding cells, but instead appears to be mediated by a reduction in the intrinsic levels of expression of TLRs and associated adaptor proteins. Because little is known about how the innate immune system develops throughout life, we next compared TLR responses in full term neonates to 7 children, adolescents and adults. We found that neonates had selective impairments in TLR responses, most notably in anti-inflammatory cytokine production and anti-viral immune responses compared to the other age groups. Epigenetic modifications, such as the addition or removal of acetyl groups to histone proteins by histone acetyl transferase (HAT) and histone deactylase (HDAC) respectively, are able to modify the expression of genes. Hence, environmental stimuli have been shown to influence gene expression in part by modifying the level or activity of these epigenetic regulators. Currently there are no studies which have examined how epigenetic modifications may influence neonatal innate immune responses. Hence, we sought to determine how modulation of endogenous HDAC activity would affect neonatal innate immune responses. We found that inhibition of HDAC had both inhibitory and enhancing effects on cytokine expression depending on the TLR pathway activated, indicating that the endogenous HDAC expression does not have a global inhibitory impact on all TLR-dependent responses. In summary, this body of work demonstrates that neonatal innate immune responses vary depending on gestational age, indicating that the final few weeks of gestation are crucial for maturation of responses to both bacteria and viruses. Neonates respond differently to TLR stimuli than do older individuals, further highlighting a maturation process of the innate immune system which continues throughout life. Finally, we have shown that environmental exposures may have powerful effects on immune responses in early life.

The aim of this study was to explore children's play, looking at developmental domains of play and gender differences in aggressive play. Chapter One reviewed existing literature on types and functions of play. Five developmental domains of play that incorporate types and functions were proposed, namely sensorimotor, cognitive, socio-communicative, imaginative/ creative and emotional. Chapter Two involved an observational study of children's play. An attempt was made to explore the existence and occurrence of the developmental domains that were proposed in Chapter One. Results suggested that the domains exist in this sample of children's play. Children statistically spent the most time in sensorimotor and imaginative/ creative play, compared to the other types of play. No statistical difference was found in gender with respects to time spent playing in the domains. Clinical implications are discussed. Future research is required to create more valid and reliable criteria for the domains and age-related norms. Chapter Three investigated gender differences in the duration of aggressive play. An observational study of children's play was carried out. The duration of time of aggessive play in each child's play was recorded and analysed. Results showed that boys displayed statistically more aggressive play than girls in this sample. Clinical implications are discussed. Chapter Four reviews the previous three chapters, looking at methodological limitations, observations of the research process and personal reflections.

Differential growth was demonstrated between facial features and within some facial features. In particular, the columella, nostrils and philtrum did not grow significantly after surgery, although this would be considered normal in the age group studied. Facial growth in children with UCL and UCLP was independent of the head and body growth. The presence of a cleft of the secondary palate accentuated the amount of soft tissue disruption by the cleft in the lip and nose, but not the pattern of disruption. Primary lip / nose repair had no detrimental effect on the early growth and development of the facial features. Likewise, palate repair had no discernible effect on facial soft tissue growth at age 2 years. Primary lip /nose repair had a beneficial effect on facial morphology in terms of reducing asymmetry and was most successful in the improving philtrum and nasal base symmetry, less successful in improving the nasal rim asymmetry. A possible early beneficial effect of cleft repair remote from the surgery site was noted in the reduction of upper face asymmetry in the first year of life. Residual asymmetry in the facial features did not change by age 2 years, despite increases in size with growth. Facial morphology outcomes for UCL and UCLP children in this study was generally similar at 2 years of age, despite marked differences in pre-operative facial form. However, nasal base asymmetry, upper face asymmetry and residual nostril shape deformity were significantly greater in UCLP children at 2 years of age, than in UCL children. These shape differences were not detectable by measurement of facial dimensions alone.