Background: Prenatal ethanol exposure (PNEE) causes irreversible intellectual and behavioral disabilities, clinically known as fetal alcohol spectrum disorder. Few neuropathologic studies of human brain exist. Hypotheses: First, markers of oxidative stress persist following PNEE. Second, PNEE is associated with inhibitory and excitatory neuron changes. Methods: Human brain autopsies (153) with known PNEE were reviewed; 18 cases (fetus to adult) and controls were selected. Oxidative stress and neuronal differentiation markers were used for immunohistochemistry. Results: There were no obvious differences between control and PNEE brains using oxidative stress markers. In human PNEE brains, glutamatergic neurons were reduced 15.96 % and 18.03% in dentate gyrus and temporal cortex, respectively. GABAergic neurons reactive for parvalbumin were reduced in all hippocampal regions (CA1= 57.86%, CA3= 65.15%, and DG= 53.39%) and temporal cortex (44.13%) in all age groups. Conclusion: GABAergic neuron reduction in human following PNEE could explain motor and behavior distractibility in FASD individuals.

Solar photovoltaic industry is a hot research field, massive attempts are going on all over the world to increase its productivity in different ways. One of the challenges for solar cells is the light spectrum mismatch losses, which referred to the part of solar spectrum that cannot be utilized to electricity by the conventional cells. Two ways have been suggested to overcome solar spectrum mismatch losses, the first is multi layered cells (tandem cells) with a different light behavior for each layer, and the second is spectrum conversion which is this researches subject. Spectral modification or conversion in solar cells industry has been studied and different lab scale models have been introduced. According to nanoscale journal, such technology may be the base of the next generation solar cells, mentioning specifically the use of luminescence down conversion and up conversion techniques to control the light spectrum on the solar cell, these endeavors targets to produce solar cells that is not subjugated to Shockley-Queisser maximum efficiency limit of 31%. This research aims to draw a map of various ideas introduced to incorporate similar technologies in solar cell products, beside further suggestion to enhance its technical behavior and to push the commercialization of the technology forward. This is expected to reveal clear image about technology’s future development map for the upcoming studies, and to create a motivation for further studies towards a commercial production scale. The proposed commercialized model will result in enhancing the maximum theoretical efficiency limit to 48% if all spectral mismatch loses have been eliminated. Quantum energy level diagrams have been illustrated to describe each model’s performance under a theoretical light spectrum.

published_or_final_version / Paediatrics and Adolescent Medicine / Master / Master of Medical Sciences

published_or_final_version / Public Health / Master / Master of Public Health

While a stable diagnosis of Autism Spectrum Disorders can be made as early as 2 years of age, the diagnosis of mild ASD cases are usually not made until primary school age or much later; and yet it is these milder cases that can benefit the most from early intervention. The present study aimed at pushing the identification of mild ASD children earlier to preschool age. A review of current screening tools revealed that they were not effective in identifying milder ASD variants. One reason perhaps is that the existing tools rely primarily on parental reports. Note that young children with mild ASD often function adequately interacting with an adult who knows them well; they typically face more difficulty in free play with other children. Parents as a result may not be in a good position to detect milder ASD. The present study therefore took a very different approach from existing screening tools by developing a more objective scale based on observation by of peer interaction in preschools. Considering peer interaction deficits are central for ASD, and deficits of these milder individuals might be more obvious in a setting that tax their social skills. A screening tool based on peer interaction observation in preschool, namely the Structured Classroom Observation Scale (SCOS), was thus developed. Drawing on existing screening tools and experts input, 84 items were compiled and pilot tested. An initial psychometric study of the scale was conducted using a community sample, with 304 preschoolers aged 3 and 4, from four English-language international schools in Hong Kong. The initial 84-item version was trimmed substantially to result in a user-friendly 13-item observation scale with good psychometric properties. The final SCOS includes 3 items depicting self-regulation challenges and 10 items describing difficulties in peer interaction. The initial psychometric study using a community sample indicated substantial interrater reliability (u= .76) and acceptable test-retest reliability (ICC = .72). The average agreement for individual items was less satisfactory (T = .40). Using Latent Class Analysis, the present scale delineated the children into 4 groups: Typical, Shy, Behavioral and High Risk of ASD. A subsequent validity study (n = 186) comparing the SCOS with ADOS scores showed that the class membership of the children based on SCOS predicted their ADOS results, after controlling for age and gender. Children from the High Risk group were found to have significantly higher Calibrated ADOS Severity scores than the other 3 groups; and their mean ADOS scores (i.e., 8.18) were above the cutoff for ASD on the ADOS. A 9-month follow found more reports of parental concerns in the High Risk group with ADOS scores above the cutoff. Discriminant validity of the SCOS was demonstrated between the scale and Head Start Competence Scale (parent version). In contrast to the usual portrayal of active but odd stereotypical children with Asperger Syndrome, the High Risk group identified by the SCOS consisted of children with infrequent interfering behaviors. They were relatively passive but not necessarily odd during social interactions, which might perhaps explain why early identification was difficult. The current scale also identified another two groups of children (Shy group and Behavioral group), which will require longitudinal follow up to ascertain educational or intervention implications. / published_or_final_version / Clinical Psychology / Doctoral / Doctor of Psychology

Background: The Weak Central Coherence (WCC) account of autism spectrum disorder (ASD) proposes a weakness of global integrative processing (i.e. central coherence) resulting in a strength in local, detailed, focused processing in individuals with ASD. However, because of the mixed findings regarding weaknesses in global integrative processing, recent literature had neglected this part of the WCC theory. Mixed findings about global integrative deficits in ASD came about because WCC was operationalized differently in different studies. This research’s primary aim was to delineate the nature of integrative processing that is impaired in ASD more precisely. Integrative processes were demarcated into first order and second order processes. Individuals with ASD were hypothesized to have problems in second order integrative processing only, which refers to the apprehension of inter-elemental relations that exist external to the individual elements. The hypothesis was investigated in both the visual-perceptual domain (Study One) and the verbal-conceptual domain (Study Two). In the visual-perceptual domain, first order and second order integrative processing refer to global processing and gestalt processing respectively. In the verbal-conceptual domain, they refer to the apprehension of taxonomic relations and thematic relations respectively. With better delineation of the construct of integrative processing in WCC, Study Three pursued the secondary aims of this research: to use the clarified constructs to study whether WCC exists as a central mechanism, and to test its predictive value on ASD symptomatology. Methods: Twenty high functioning adolescents with ASD (HFA, aged 12 to 15) and 20 matched typically developing (TD) counterparts (aged 12 to 15) participated in the three studies of this research. In Study One, participants were administered a first order task with hierarchical compound stimuli that aimed to tap their global processing, and a second order task that aimed to tap their apprehension of gestalt principles (gestalt processing). In Study Two, participants were administered a lexical decision priming task with half of the prime-target pairs denoting a taxonomic relation (first order task), and half of the prime-target pairs denoting a thematic relation (second order task). In Study Three, correlation analyses were done among the second order task measures of the two domains as well as HFA symptomatology indexed by the Autism Quotient (AQ). Results: For Study One, there was a trend showing that participants with HFA performed worse than TD peers in a subtask that tapped one gestalt principle (the principle of similarity). Contrary to prediction, in the global processing task, HFA individuals exhibited a reliable local bias. For Study Two, HFA participants were found to be primed to a significantly lesser extent by a thematic prime while exhibiting intact taxonomic priming. In Study Three, cross domain associations of second order processing measures were not significant, which was against the notion of a central mechanism of WCC. The priming extent by a thematic prime and a measure of gestalt processing were found to associate negatively with ASD symptoms in the TD group. Conclusions: All in all, the present research had partial success in clarifying the nature of WCC as a weakness in second order integrative processing. Theoretical and practical significance as well as future research directions were discussed. / published_or_final_version / Educational Psychology / Doctoral / Doctor of Psychology

Valproic acid (VPA) is a broad-spectrum anticonvulsant and antiepileptic drug and widely used in many neurological conditions and psychiatric disorders as well as in cancer and HIV treatment. However, despite all its many benefits, VPA also has side effects. It is a strong fetal teratogen that can induce congenital malformation and neurodevelopmental problems. Case reports and population studies have revealed that prenatal exposure to VPA is associated with a higher risk of autism in postnatal life. Animal models also have confirmed that VPA can induce autistic-like features in rodents. Yet, there are some questions remaining unanswered by existing animal studies of prenatal VPA exposure. The embryotoxicity of a drug is not only determined by its own chemical, physiological or pharmacological properties, but also on the dose and the time in development that the exposure happens. The majority of studies investigating the behavioral, neuroanatomical and physiological impact of VPA in animals have examined early gestational exposure to relatively high doses that can cause significant malformation or loss of offspring. Thus, although there are behavioral alterations considered similar to autistic symptoms in humans, these are found in the offspring that have survived a very toxic insult, leading to problems of interpretation. Low dose exposure has not been widely studied, nor has the impact of VPA exposure late in gestation. Moreover, how the age and sex of offspring influences the phenotypic outcome has rarely been considered. Therefore, in the present series of studies, a battery of behavioral tests and in vivo magnetic resonance imaging (MRI) was used to investigate the postnatal consequences of prenatal exposure to lower doses of VPA in mice in early and late gestation. The effects of VPA were examined in female and male mice at juvenile and adult ages. The main findings were, that low doses of VPA in early or late gestation cause no physical malformation and no gross neurological functional impairments, but induce behavioral abnormalities and neuroanatomical differences related to autism. Generally, VPA-treated mice exhibited lower motor activities and higher anxiety levels in the open field test; dislike of novelty in the novel abject exploration test; higher startle response and sensorimotor gating differences; decreased responses to non-social and social odors in the olfactory test; and volumetric changes in brain structures similar to those found in autism. However, the timepoint of exposure, dose of VPA, sex and age of testing influenced the phenotypic outcome. Although largely neglected in previous studies, late gestation exposure to VPA elicited an autistic phenotype. Surprisingly, given the male bias in autism, female mice were often more ‘sensitive’ to VPA. Although the present studies had some limitations, these experiments confirmed that low dose VPA in pregnancy could trigger behavioral abnormalities and brain anatomical differences in mice that resembled a range of features of autism. Importantly, these behaviors were unconfounded by ‘gross’ neurological or physical abnormalities. Further studies to investigate the cellular mechanisms underlying the low dose VPA phenotype will therefore be helpful to shed light on possible causal pathways with specific relevance to autism. / published_or_final_version / Psychiatry / Doctoral / Doctor of Philosophy

Objective: To present a systematic review of existing literature that investigates biological plausibility of prenatal hazardous air pollutants’ (HAPs) exposure, in the etiology of autism spectrum disorder (ASD) and related outcomes. Method: Electronic databases Pubmed, Biomed Central and National Database for Autism Research, and grey literature pertaining to air pollution association with ASD and related outcomes were searched using specific keywords. The search included 190 HAPs as defined by The Clean Air Act Amendments of 1990 [U.S.Environmental Protection Agency (EPA) 1994] including air pollutants CO, SO2, NOx, O3 and Particulate Matter (PM). Studies selected for systematic review were assessed on quality and causality. Result: Total of 628 articles from electronic search and 16 articles from grey literature were retrieved. 12 studies that cleared the inclusion and exclusion criteria were systematically reviewed using the PRISMA checklist. Outcomes considered included ASD, Attention Deficit Hyperactivity Disorder, social behavior, social interaction, child behavior, communication, cognitive development, attention problems, mental and psychomotor development, and social competence. Studies were from two countries, United States of America and Spain. Study design was case control and cohort study. Follow up duration for cases ranged from in-utero to less than 9 years. Exposure was measured in ambient air using predictive models and cord blood. Although there were discrepancies in the studies, related to strength of association, analysis and covariates adjusted, the association between air pollution and ASD related outcomes could not be dismissed. Most studies lacked information on blinding when quality was assessed and lacked consistency when assessed on causality, while scored well on temporality and biological plausibility. Discussion: Evidence suggests HAPs are capable of transplacentally affecting cognitive function, especially traffic related pollutants. Study design, sample size, response rate, exposure misclassification, failing to adjusting covariates related to lifestyle, nutrition and other chemical exposures have influenced the estimates and the strength of association. Shortcomings of this review are the English language restriction and single reviewer on study selection process and assessments. Immuno-toxic, neuro-toxic and endocrine disrupting properties of these HAPs necessitates comprehensive prospective studies especially in Hong Kong with the rising prevalence of ASD and ever high reported air pollution indexes. Conclusion: Repeated studies were carried out on the same cohorts and studies were concentrated in U.S.A. On account of a lack of consistency, it is difficult to confirm whether air pollution is a plausible candidate for prenatal exposure in ASD. (Abstract of 391 words) / published_or_final_version / Public Health / Master / Master of Public Health

With the increased requirement on the ultrafast measurement technology, how to resolve the spectral dynamics has the top priority on the research list, since spectrum is an essential carrier for most of the physical or chemical phenomena. According to the Nyquist-Shannon sampling theorem, if a function 𝑥(𝑡) contains no frequencies higher than 𝐵 Hz, it is completely determined by giving its ordinates at a series of points spaced 1/(2𝐵) seconds apart. Since most of the conventional optical spectrum analyzers (OSAs) are operated with the sampling rate (or frame rate) of 5 Hz, it results in the resolvable bandwidth of the spectrum dynamic is less than 2.5 Hz. With the development of the space-time duality, the analogy transforms the conventional spatial dimension into the time axis, and the well-known spatial models inspire us in performing their counterparts in the time domain. As one of the most powerful tools in achieving ultrafast time axis information, time-lens plays a more and more important role in the single-pixel imaging system. By fully analyzing the diploma of the previous optical spectrum resolving mechanisms, in this thesis, for the first time, we raised up the concept the parametric spectrotemporal analyzer (PASTA), which is based on the time-lens focusing mechanism. Here the spectrum resolving frame rate is increased to 100 MHz, then the observable spectrum dynamic bandwidth could be 50 MHz, which is sufficient for most of the ultrafast phenomena. In the PASTA system, the time-lenses are implemented with the fiber optical parametric amplifier (FOPA) based parametric mixer, which provides higher conversion efficiency and repetition rate. On the other hand, the dispersion based dispersive Fourier transformation (DFT) technology generates the swept-pump for the FOPA, as well as the temporal dispersion medium. This research in this thesis is a fundamental study on the newly PASTA system, from its origin and the theoretical background, to the implementation techniques and operation performances. From its implementation, its principles are strongly related with the combination of the dispersion and the Kerr nonlinear effects, especially the swept-pump FOPA in the time-lens part. The DFT technique, in generating the fast swept-source, has also find its applications in the ultrafast serial time-encoded amplified microscopy (STEAM) and swept-source optical coherence tomography (SS-OCT) systems. Finally, the single-lens PASTA prototype is capable of resolving 5-nm wavelength range with 0.03-nm resolution under 100-MHz frame rate. Moreover, besides the singlelens PASTA, the telescope/wide-angle configurations have also been investigated experimentally to achieve the spectrum zoom in/out ratio as high as 17 times, here we have obtained the sharpest resolution of 5 pm (<1 GHz) with the telescope configuration, and the widest observation range of 9 nm with the wide-angle configuration. My research efforts presented in this thesis mainly leverage the ultrafast characteristics of the time-lens system, from theory to implementation, and achieve the real-time optical spectrum analysis – the PASTA system. PASTA is not only essential in observing some non-repetitive ultrafast phenomena, but also provides a potential solution for the frequency to time transformation in some ultrafast bio-medical imaging systems. / published_or_final_version / Electrical and Electronic Engineering / Doctoral / Doctor of Philosophy

Background: Individuals with autism spectrum disorders (ASD) are characteristically deficient in social awareness and communication skills, while displaying repetitive behaviours. Because of this, integration of individuals with ASD into society is often difficult as people do not know how to respond to their atypical behaviour. Particularly in Asian cultures, this vulnerable group is often subjected to stigmatization. However, recent literature has highlighted some benefits of assistive animal intervention (AAI) for individuals with ASD, which may improve their ability for social interaction. This review examines the effects of AAI in terms of service dogs for individuals with ASD. Methods: Journal articles were identified through a systematic review on psycINFO, Pubmed, Scholars Portal and Web of Knowledge. Additional searches were conducted for inclusion of grey literature and doctoral theses in the review. Results: Of the 170 studies initially found, 7 were selected; 3 cohort studies, 3 case-control studies, and 1 cross-sectional study. Reported outcomes included increased social reciprocity, decreased behavioural problems and decreased stress in individuals with ASD. Despite these positive outcomes, they should be taken with caution, as the designs of the seven studies included in this review show methodological weaknesses, such as small sample sizes and possible information bias from data collection. Conclusions: Additional research focused on varying age groups with ASD, longitudinal studies and standardized outcome measures are required for further research. What this review suggests though is that there is a need to address social services gaps for various disability groups, not just for those with ASD. Some legislative measures are in place in Hong Kong to support the accessibility of assistance dogs in public; however, since there are so few in Hong Kong, their exposure is not enough to gain widespread acceptance. Expansion of assistance dog services to serve other disability groups may help to enhance their quality of life. / published_or_final_version / Public Health / Master / Master of Public Health