Influenza is a leading cause of respiratory disease worldwide. During pandemic and seasonal influenza, secondary Streptococcus pneumoniae infection is a severe complication that contributes to morbidity and mortality. With the clinical significance of this co-infection, it is imperative to understand the disease mechanisms and how our immune system would be modulated in dealing with the dual infection. First, in vivo co-infection model was established. Mice were sequentially infected with influenza virus and then Streptococcus pneumoniae. Co-infected mice lost their body weight significantly and had 100% mortality, whereas mice infected with either influenza virus or pneumococcus alone lost their body weight transiently and all recovered from the infection. Then, lung inflammatory response during the co-infection was examined. Although it is a common phenomenon that co-infection enhances inflammation, the kinetic of, and the relative contribution of influenza virus or pneumococcus to the lung inflammation is not well defined. Therefore, this study characterized the general lung inflammatory environment after co-infection. It was found that influenza virus and pneumococcus differentially modulated inflammatory response in terms of kinetics, leukocyte infiltration and cytokine production. At the early time point after co-infection, pneumococcal infection contributed more than the influenza virus infection to enhance inflammatory cytokine and neutrophil infiltrating the lung. At the later time point after co-infection, both influenza virus and pneumococcus contributed to synergistically increase inflammatory cytokine and macrophage infiltrating the lung. Influenza virus infection induced IFN-γ that contributed to the elevated IFN-γ level in co-infected mice. Influenza virus and pneumococcus synergistically increased Th2 associated cytokine including IL-4, IL-5, and IL-10. These up-regulated immune responses might contribute to the severe lung pathology. Next, adaptive immunity to co-infection was examined. Literature studying co-infection often reports how prior influenza virus infection impairs the immune response against subsequent bacterial infection. However, whether and how secondary pneumococcal infection would affect the immunity to the initial influenza virus is unknown. Therefore this study investigated the modulation of immunity to influenza virus by secondary pneumococcal infection. It was found that co-infection significantly enhanced virus titer in lung and depleted the number of cell in spleen. Secondary pneumococcal infection after influenza decreased influenza virus specific IgG in the lung and peripheral blood. The reduced level of virus specific IgG was associated with the decrease in the number and the percentage of follicular B cell and CD4 T follicular helper cell through both pneumococcal capsular polysaccharide dependent and independent manner. Treating co-infected mice with immune serum containing influenza virus specific IgG successfully improved survival, which suggested the important protective function of virus specific IgG to the co-infection. Taken together, these data suggested that secondary pneumococcal infection impairs the antibody response to influenza virus, which might enhance mortality after co-infection. In conclusion, this study provides new insight to understand the pathogenesis of co-infection, reveals the general lung inflammatory environment, highlights the negative role of pneumococcus to impair virus control and explores novel treatment for the co-infection. / published_or_final_version / Paediatrics and Adolescent Medicine / Doctoral / Doctor of Philosophy

Schizophrenia and autism are psychiatric disorders with a presumed neurodevelopmental origin, characterised by clinical features and aetiologies that overlap at multiple levels. In addition to genetic susceptibility, epidemiological studies revealed an association between environmental factors and these disorders. Immune activation in response to infection at early gestation has been identified as one of the key risk factors. Little is known about the underlying mechanism during maternal immune activation (MIA), but extrinsic apoptotic dysregulation has been postulated to play a role in MIA infection. In particular, emerging studies suggest apoptosis without triggering whole cell demise, namely synaptic apoptosis, is a potential event that leads to the abnormal behaviours in the affected offspring. In this study, C57BL/6N mice model was employed to investigate the impacts of viral mimetic polyriboinosinic-polyribocytidylic acid (Poly I:C) exposure at gestation day 9 in the resultant male offspring in adulthood in vivo by different parameters, including magnetic resonance imaging (MRI), behavioural tasks that assess sensorimotor gating, exploratory and anxiety behaviours, and protein quantification in the apoptotic pathway. In parallel, the direct effect of Poly (I:C) treatment for 24 hours on extrinsic apoptotic proteins were determined in primary cortical neurons in vitro. It was hypothesised that MIA would result in brain volumetric changes subsequent to behavioural anomalies in the adult offspring with maternal exposure to Poly (I:C), for which abnormalities are normally pronounced by that time. In addition, the hypothesis that foetuses exposed to Poly (I:C) in early gestation stage would have increased expression level of apoptotic proteins of extrinsic types, namely Fas receptor, caspase-8 and the death effector caspase-3. This study found that, although male adult offspring with early maternal exposure to Poly (I:C) had an increase in raw whole brain volume, this was not significant when body weight was included as a covariable. However, prenatal exposure caused behavioural features similar to those reported in schizophrenia and autism such as prepulse inhibition deficits, increased anxiety-level and higher locomotor activity in response to amphetamine challenge. On the other hand, a marked augmentation in caspase-8 level without any significant changes in Fas or caspase-3 was observed in the adult hippocampus. No alterations in the expression of selected apoptotic proteins were found in the embryonic cortical cells. Overall the present studies suggested that acute exposure to infection during early fetal development causes a range of aberrations in brain anatomy, behaviour and biochemistry that are of relevance to the pathophysiology of schizophrenia and autism. The results suggest a potential involvement of synaptic apoptosis in cellular events underlying neurodevelopmental disorders. / published_or_final_version / Psychiatry / Master / Master of Philosophy

abstract / Business / Doctoral / Doctor of Philosophy

Background: Unhealthy lifestyle are important contributors to chronic illness in Hong Kong and worldwide. Lifestyle modification, particularly improving healthy diet and physical activity, can prevent the development of various chronic illnesses, improve disease conditions, reduce the risk of complications and enhance the quality of life. Many behavioural models have been applied to achieve lifestyle modification, but the major limitation was that they mainly treated human behaviours as individual behaviours that were subsequent to rational thinking. Nudge theory, an advanced behavioral concept, proposed to change individual’s motivation, incentives and decision making through non-direct suggestion and non-forced reinforcement. However, the application of Nudge theory has been challenged on the lack of evidence to prove its effectiveness, and its controversial framework for ethical analysis. Objectives: This review was to synthesize the empirical findings about the effectiveness of using nudge theory for lifestyle modification including healthy diet and physical activity. Methodology: Interventional and experimental studies that were conducted based on Nudge theory to change diet or physical activity was identified from the published literature. The studies were divided into two large groups according to outcome measured: healthy diet and physical activity, and they were systematically synthesized. The “nudges” used in these studies were categorized as six types of “nudges” summarized by “nudge unit” as “MINDSPACE” for further discussion. The type of “nudges” that were used in the studies and their effectiveness on changing diet and physical activity was abstracted. Results: Totally, nine articles that met the inclusion criteria were included. Five nudges were identified from the included studies, including Priming (P), Default (D), Salience & Affect (SA), Incentives (I) and Messenger & Norms (MN). It is found that the strategies and methods applied on the same nudge may have different effectiveness. Seven studies applied Priming (P) as nudge to motivate change in diet, which used two major strategies: “availability” and “accessibility”. The evidence was strong that altering the availability of food presence could be effective to change food selection. The results of studies using accessibility were heterogeneous and contradictive with each other. Another three studies used different nudges including Default, Salience & Affect and Incentive. The effectiveness of Default (D) as nudge seemed to be blurry, and the sustainability remained questionable. The ethical consideration is always the primary pillar for applying nudging theory. As long as the applications are stick to necessary ethical concerns, the nudging model can be beneficial through mild “manipulation” rather than harmful. Conclusion: It has potential opportunity to carry out “libertarian paternalism” in Hong Kong. However, it is still a long way to take application of nudging model into regulation, legislation and daily practice. The evidences for each type of nudge were not consistent and enough. Besides, the monitoring and evaluation are not available yet. Future research can be focused on transferring these applications into real practice with an effective monitoring and evaluation system. / published_or_final_version / Public Health / Master / Master of Public Health

Six experiments were conducted in order to examine the role of movement specific reinvestment in performance of a range of tasks of varying complexity under different performance contexts. The first experiment investigated the role of movement specific reinvestment in performance of a fundamental laparoscopic skill under time pressure. It was found that individuals with a lower propensity for movement specific reinvestment were able to meet task demands by performing faster under time pressure than individuals with a higher propensity for movement specific reinvestment. Although movement specific reinvestment is often treated as a uni-dimensional construct, it is comprised of two dimensions of conscious processing; movement self-consciousness and conscious motor processing. These dimensions appear to exert a differential influence on performance in different contexts. The second experiment therefore investigated the differential influence of the two dimensions of movement specific reinvestment on performance of a fundamental laparoscopic skill early and later in practice and on performance of a more complex, cross-handed laparoscopy task. Movement self-consciousness was found to play a more dominant role early and later in practice of a relatively simple, fundamental, laparoscopic skill than conscious motor processing, which played a more dominant role in performance of a more complex, cross-handed laparoscopic skill. The third and fourth experiments examined the differential influence of the two dimensions of movement specific reinvestment on a complex golf-putting skill early and later in practice (Experiment 3) and under low- and high-anxiety conditions (Experiment 4). Experiments 3 and 4 also examined the kinematic mechanisms underlying the influence of the two dimensions on putting performance. Findings from Experiment 3 revealed that movement self-consciousness and conscious motor processing positively influenced putting performance early in practice, when learners were consciously engaged in the control of movements. However, later in practice movement self-consciousness alone positively influenced putting performance. Analysis of kinematic measures suggested that reduced variability of both impact velocity and putter face angle at impact mediated the positive influence of both movement self-consciousness and conscious motor processing on putting performance. Findings from Experiment 4 revealed that movement self-consciousness positively influenced performance in the low-anxiety condition (and appeared to reduce variability of impact velocity), but not in the high-anxiety condition. It was argued that the attention demanding nature of anxiety (Eysenck & Calvo, 1992) potentially subdued the influence of movement self-consciousness under high-anxiety conditions. The fifth experiment confirmed this proposition as the positive influence of movement self-consciousness on quiet standing performance was no longer evident when an attention demanding dual-task was performed concurrently with a primary quiet standing task. The final experiment examined the unique influence of the two dimensions on laparoscopic performance during practice and under anxiety in a real-world anxiety provoking situation, the objective structured clinical examination (OSCE) (Muldoon, Biesty, & Smith, 2014; Nasir et al., in press). The findings of the six experiments are discussed within the framework of the Theory of Reinvestment (e.g., Masters, 1992; Masters & Maxwell, 2008). / published_or_final_version / Human Performance / Doctoral / Doctor of Philosophy

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This dissertation applied mass communication theory and the interdisciplinary theory of social network analysis to the networked political blogosphere and its relationship to mass media. Utilizing such mass communication theories as agenda setting, the two-step flow, and gatekeeping, this study examined eighteen political blogs across the political spectrum (left-leaning, right-leaning, and moderate blogs), two elite mass media outlets (the New York Times and the Washington Post), and two elite mass media blogs (political blogs from the New York Times and the Washington Post), using both hyperlink analysis as well as textual content analysis. Hyperlinking provided information on gatekeeping and the social network connections between blogs and mass media and among the different ideological political blog networks. Content analysis conducted at the issue and the issue attribute level provided a second layer of evidence to analyze how agendas are formed, framed, and transferred in the emerging new media environment. All the both levels of textual content analysis and hyperlink analysis, this dissertation found solid support for the operation of both mass media agenda setting and social network influence at both the issue and the attribute level. Though the agenda setting function of the press is still a tenable assumption, blogs from all ideological spectrums were able to set the mass media's agenda. The issue agendas of blogs of shared partisan perspective, particularly the agenda of the left-leaning blogosphere, provided strong evidence of homogenous issue adoption by blogs of the same partisan network neighborhood or social network. At the attribute level, strong correlations between the agendas of blogs and media, and among the agendas of blogs that share ideological perspectives, highlight the need for deeper analysis at causation to determine whether the media or blogs set each other's agenda. This dissertation contributes to mass communication studies and political communication through its identification of political social networks as a complementary and competitive agenda setting force in the context of the US political blogosphere. These findings call for a revision of the relationship between agenda setting and the twostep flow theory towards an acknowledgement of how they work in both complementary and competitive ways to redefine the role of the press and social influence in networked political environments. These findings also highlight the significance of social network analysis as a methodology to explain how agendas are formed and framed in the emerging new media environment.

The present investigation was designed to elucidate the potential influence of age on speech breathing. Toward this end, 30 men representing three widely different age groups (25, 50, and 75 years) were studied. These individuals were carefully selected to meet stringent criteria, the most important of which related to health and physical characteristics. Speech breathing was studied via anteroposterior diameter changes of the rib cage and abdomen. Recordings were made during extemporaneous speaking and reading and during the performance of various chest wall maneuvers used in the measurement of the speech breathing data. In addition to speech breathing, selected measures of general respiratory function were obtained. These included measures of subdivisions of the lung volume and measures of resting tidal breathing. Results indicated that these 30 subjects were representative of other subjects studied with respect to measures of general respiratory function. Subdivisions of the lung volume were found to differ with age in the manner predicted by previous investigations. Age-related differences were most marked for measures of vital capacity and residual volume. By contrast, there were no age-related differences for measures of resting tidal breathing. Several speech breathing measures were found to differ with age. Age-related differences were usually between the 25- and 75-year-old subject groups and less commonly between the 25- and 50-year-old subject groups. For extemporaneous speaking, differences were found for lung volume excursion, rib cage volume initiation (referenced to the rib cage volume associated with the relaxed configuration of the chest wall), number of syllables per breath group, and lung volume expended per syllable (in percent vital capacity). For reading, differences were found for lung volume expended per syllable (in percent vital capacity). Age-related similarities and differences in general respiratory function and speech breathing are discussed in relation to possible underlying mechanisms. In addition, implications are drawn regarding evaluation and management of individuals with speech breathing disorders.

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