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Implementation science: Training community speech therapists to conduct evidence-based treatment for children with childhood apraxia of speech
No full textIntroductionChildhood apraxia of speech (CAS) is a pediatric motor speech disorder requiring specialized assessment and treatment. Identifying CAS in Cantonese speakers is challenging, and local speech therapists (STs) may struggle to implement research-based treatments despite their training, which is typically based on the English literature. This project aims to provide intensive training to local STs on research-based assessment and treatment, and to evaluate its effectiveness.MethodsSix clinicians (five practicing STs and one student ST) participated in pre-clinical and clinical training. Pre-clinical training included 8 hours of online tutorials and a one-day workshop, requiring completion of five modules with quizzes. The workshop involved practical exercises, submission of videos, and reflective essays. Clinical training focused on assessment and DTTC treatment for children with CAS, with outcome measures including quiz scores, pre-/post-workshop surveys, and treatment fidelity.ResultsThe project is ongoing. All participants have passed the pre-clinical training, and the ST student has completed the clinical training. The whole group of STs averaged 11.6 total attempts across the six quizzes. The ST student has finished treatment with one participant, with 90% fidelity. On the pre- and post-workshop surveys, the six participants’ average confidence ratings for implementing DTTC treatment were 2.5 and 3.0 (out of 4), respectively. Additionally, participants provided more detailed lists of important components of the treatment in the post-workshop survey compared to the pre-workshop one.DiscussionThis project offers an effective protocol for training local STs in CAS assessment and DTTC treatment. Preliminary fidelity measures indicate that the training has aided clinicians in applying research-based assessment and treatment. Future studies could explore using this protocol in other ST-related treatment programs.</p
Dynamic Temporal and Tactile Cueing in a Cantonese-English Bilingual Child
No full textThis study investigates the efficacy of Dynamic Temporal and Tactile Cueing (DTTC) for a Cantonese-English bilingual child with childhood apraxia of speech (CAS). Using an ABACA design, the child underwent 12 sessions in both languages. Outcomes will focus on segmental accuracy, prosodic accuracy, and speech intelligibility, with results to be presented in July 2025.</p
The corrosion behaviors of Inconel 718 fabricated by additive-subtractive hybrid manufacturing in marine environment
No full textDue to the different timing of the intervention in subtractive manufacturing (SM), additive-subtractive hybrid manufacturing (ASHM) primarily includes two subtractive methods: high-temperature milling (HTM) and room-temperature milling (RTM). In the present work, the passive film characteristics and corrosion behavior of Inconel 718 samples prepared by additive manufacturing (AM) and ASHM (including HTM and RTM) were investigated using microstructural, residual-stress, electrochemical, and X-ray photoelectron spectroscopy analyses. Due to the formation of nano-grained microstructure and residual compressive stress introduced by AM, the ASHM-fabricated samples did not undergo obvious stress corrosion cracking after polarization reaction. Furthermore, a significant increase in grain boundary density led to a higher proportion of oxides in the passive film of ASHM-fabricated samples than that of AM-fabricated one, thus improving the film's compactness and chemical stability. Compared to AM and HTM samples, RTM sample showed the highest grain boundary density, thickest passive film, minimal defects, and superior overall corrosion resistance. </p
DNA repair gene SNPs and radiosensitivity in lung cancer : from systematic review, meta-analysis to biology exploration
No full textpublished_or_final_versionClinical OncologyMasterMaster of Research in Medicin
The anti-fibrotic and pro-healing effects of topical lycium barbarum polysaccharide (LBP) treatment in an in vivo alkali-induced corneal epithelial-stromal injury model
No full textCorneal opacification ranks fourth in the aetiologies of blindness worldwide. In clinical
practice, topical pharmacological therapies for corneal opacity - namely mitomycin-C and
corticosteroids - could result in unwanted side effects involving increased intraocular pressure
and scleral necrosis. Lycium barbarum polysaccharide (LBP) taken from Goji
berry demonstrated anti-fibrotic properties in vitro. This suggested its capacity of addressing
corneal fibrosis. The present study implemented a mouse epithelial-stromal alkali injury model
to evaluate LBP's efficacy in reducing opacity and expediting epithelial healing.
C57Bl/6J wild-type mice (n=6) were used in the present study. 1.5 mm-diameter circular filter
paper soaked with 0.5M NaOH was placed onto the centre of right cornea under sedation for
45 seconds, followed by irrigation using filtered water. Mice received topical application of 2
or 20 mg/mL LBP while PBS was applied to control group. The topical treatments were applied
in 3 modalities: before alkali injury (pre-injury treatment), after alkali injury (post-injury
treatment), and both before and after alkali injury (pre-post-injury treatment). Pre-injury
treatment lasted for 7 consecutive days prior to injury. Post-injury treatment lasted for 7
consecutive days after injury. Pre-post-injury treatment included 7 days before and 7 days after
injury. On Day 0, 1, 2, 3, 7, 14, 21, and 28 post-injury, mice corneas were examined by slitlamp
microscopy. Modified Fantes score (0-4) was used to grade opacity, while estimated
epithelial defect was calculated from fluorescein staining. Corneal thickness was evaluated by
histology and expression of fibrotic markers such as fibronectin was examined by
immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). 0.5M NaOH was found to induce consistent corneal opacification with increased central
corneal thickness and deposition of fibronectin in stroma. Pre-post-injury treatment with 2 and
20 mg/mL LBP significantly reduced corneal opacification. The modified Fantes score on Day
28 was 2.00 and 1.67 respectively, compared to the score of 3.17 in the PBS control group (p
< 0.0245; p < 0.0051). 2 and 20 mg/mL LBP pre-post-injury treatment also accelerated reepithelialisation
on Day 1, with estimated epithelial defect area of 0.06 } 0.14 mm2 and 0.05 }
0.11 mm2 respectively, compared to 0.45 } 0.15 mm2 in the PBS control group (p < 0.05).
Histology results revealed that 20 mg/mL LBP pre-post-injury treatment reduced total corneal
thickness and ELISA results showed reduced corneal fibronectin expression on Day 28.
Immunohistochemistry staining was negative for collagen type III, alpha-smooth muscle actin
(α-SMA), and vimentin in all corneal samples.
Given its anti-fibrotic and pro-healing properties, LBP has the potential of becoming a topical
pharmacologic regimen for the treatment and prevention of corneal opacification in relation to
alkali injury. Further investigations such as underlying mechanism are required to facilitate
LBP’s translation into clinical practice.published_or_final_versionOphthalmologyMasterMaster of Research in Medicin
Compositional programming in action
No full textCompositionality is an important principle in software engineering, meaning that a complex system can be built by composing simpler parts. However, achieving compositionality in practice remains challenging, as exemplified by the expression problem -- a well-known dilemma that highlights the tension between modularity and extensibility. CP, a new statically typed programming language, naturally solves such challenges through language-level support for compositional programming.
This thesis mainly studies the practical aspects of CP. We start with a crash course in CP and showcase why compositional programming matters with two applications. First, regarding object-oriented programming, CP innovates with a trait-based model with merging that prevents implicit overriding in inheritance. By comparing with type-unsafe code in TypeScript, we show that CP achieves dynamic multiple inheritance and family polymorphism without sacrificing type safety. Second, regarding domain-specific languages, CP enables a novel embedding technique that combines the advantages of shallow and deep embeddings and surpasses other techniques like tagless-final embeddings by supporting modular dependencies.
Next, we detail the design and implementation of the CP compiler. With novel language features for compositionality, the efficient compilation of CP code is non-trivial, especially when separate compilation is desired. Our key innovation is to compile merges to type-indexed records, which outperforms prior theoretic work based on nested pairs. To maintain type safety in trait inheritance, CP's type system employs coercive subtyping, which incurs a performance penalty in compiled code. We mitigate the issue with several optimizations, including eliminating coercions for equivalent types. We evaluate the impact of these optimizations using benchmarks and show that the optimized compiler targeting JavaScript can be orders of magnitude faster than a naive compilation scheme, obtaining performance on par with class-based JavaScript programs.
Finally, we extend CP with union types, complementing ubiquitous intersection types, in order to provide a solid foundation for named and optional arguments. Our approach resolves a critical type-safety issue found in popular static type checkers for Python and Ruby, particularly in handling first-class named arguments in the presence of subtyping. A detailed comparative analysis of named and optional arguments in existing languages shows that CP's design achieves a good balance of simplicity and effectiveness.
Both the compilation scheme for CP and the encoding of named and optional arguments are formalized in Coq and proven to be type-safe.published_or_final_versionComputer ScienceDoctoralDoctor of Philosoph
Exploring statistical methods for estimating heritability, functional enrichment and polygenic risk score using GWAS summary data in complex traits
No full textGenome-Wide Association Studies (GWAS) have catalyzed a paradigm shift in our comprehension of the genetic foundations of numerous diseases, uncovering over 50,000 significant associations between genetic variants and common diseases or traits. These pivotal discoveries have not only shed light on previously unknown disease-causing genes and mechanisms, but have also accelerated advancements in personalized medicine, facilitating the identification of new drug targets, disease biomarkers for early detection and monitoring, and risk prediction, along with the development of therapies tailored to individual genotypes. This thesis accentuates the importance of post-GWAS analysis, particularly in the estimation of heritability, functional enrichment, and polygenic risk scores from GWAS summary data.
This thesis commences with a succinct review of the standard GWAS procedure, along with a description of the background of SNP heritability estimation and polygenic risk scores (PGS) calculation in post-GWAS analysis. Following this, a brief literature review of existing methods with similar objectives is provided. Within the scope of this work, two innovative software tools are proposed. The first, dubbed as generalized-LD score regression (g-LDSC), partitions SNP heritability to estimate functional enrichments. This tool capitalizes on the correlation between -statistics and the squared LD matrix, distinguishing itself from s-LDSC by employing feasible generalized least squares (FGLS) estimation to account for potential correlated error structures. Our simulation studies under various scenarios illustrate that g- LDSC furnishes more precise estimates of functional enrichment than the prevailing method, irrespective of model misspecification. When applied to GWAS summary statistics of 15 traits from the UK Biobank, estimates of functional enrichment using g-LDSC were found to be more conservative and realistic than those derived from s-LDSC. Moreover, g-LDSC identified a greater number of significantly enriched functional annotations among 24 functional annotations for the 15 traits than s-LDSC (118 vs. 51). The second software tool, termed as best subset selection using GWAS summary statistics (BSsum), employs norm-based penalized regression methods to estimate PGS. Through simulation studies under diverse scenarios, we demonstrate that under high-sparsity, low-polygenicity scenarios, the norm holds an edge over the norm. These groundbreaking statistical tools hold the promise to further refine the extraction of valuable insights from GWAS data, thus driving genetic research to unprecedented heights.published_or_final_versionPsychiatryDoctoralDoctor of Philosoph
Navigating sustainability challenges : three essays on climate change, ESG rating, and geopolitical conflicts
No full textThe growing focus on sustainability challenges has elevated the need to coordinate solutions and adaptations to address them. A series of recent studies have explored the roles and responsibilities of organizations such as firms and related stakeholders in orchestrating efforts to address these challenges. To add to this stream of literature, I conduct three studies to explore how organizations navigate sustainability challenges.
The first essay explores how firms strategically outsource their carbon emissions to suppliers in response to physical climate change exposure. By analyzing a panel dataset comprising 3,763 U.S. firms between 2001 and 2021, we find that a firm’s physical climate change exposure is negatively related to its carbon emissions but positively related to its supplier’s carbon emissions, leading to an insignificant effect on the overall emissions. We use the most damaged hurricanes as quasi-exogenous climate shocks and focus on firms that are headquartered in the neighborhood of the disaster area to address alternative explanations. Further mechanism tests support our logic that physical climate change exposure heightens both managers’ and stakeholders’ climate change awareness, which induces firms to outsource carbon emissions to suppliers. We contribute to the research on climate change and pollution outsourcing.
The second essay investigates how ESG investors can take advantage of ESG rating ambiguity to rationalize controversial investment decisions so that these decisions can appear simultaneously congruent with incompatible institutional demands from the financial logic and the social logic inherent in ESG investing. We analyze a panel dataset comprising 7,248 firms across 67 countries between 2006 and 2021, focusing on green stocks and sin stocks that exemplify incompatible institutional demands. We find that ESG rating ambiguity increases ESG ownership in sin stocks, an effect strengthened by the maximum score of the multiple ratings, and decreases ESG ownership in green stocks, an effect strengthened by the minimum score of the multiple ratings. Our findings remain, using a difference-in-differences analysis based on a regulatory shock. These findings contribute to the literature on institutional theory and ESG ratings.
The third essay explores how firms increase social skill hiring in response to geopolitical conflicts. As geopolitical conflicts introduce substantial uncertainties into the global supply chains, firms often respond to such conflicts through relocation or reshoring strategies. Extending prior research, we propose an alternative strategy for firms to navigate geopolitical conflicts and stabilize their supplier partnership, i.e., social skill hiring, because employees with strong social skills are crucial in managing and maintaining partnerships amid geopolitical conflicts. Using the U.S.-China trade war as an exogenous shock, our difference-in-differences analysis reveals that U.S. firms exposed to the trade war increase their hiring of employees with social skills. Our mechanism tests show that social skill hiring is greater when firms have a higher number of Chinese suppliers or a more dispersed supply base. Further analysis shows that firms with more social skill hiring experience greater stability with Chinese suppliers in the post-trade-war period. These findings contribute to the research on trade war and social skill hiring.published_or_final_versionBusinessDoctoralDoctor of Philosoph
Lifestyle factors and novel biomarkers in cardiometabolic diseases
No full textCardiovascular diseases (CVDs) are the leading cause of death worldwide. Socioeconomic factors, obesity, unhealthy diet, smoking and genetic factors are known as CVD risk factors. Metabolic syndrome (MetS) has been found to significantly increase the risk of CVDs. According to recent guidelines, promoting lifestyle interventions and weight management is essential. The measurement of novel biomarkers including fibroblast growth factor 21 (FGF21), lipocalin-2 (LCN-2), cystatin C, beta-2 microglobulin (B2M) and neurofilament light chain (NfL) may also provide valuable support for assessing CVDs and MetS.
Four studies in this thesis used the data from the Shenzhen-Hong Kong United Network on Cardiovascular Disease (SHUN-CVD), which is a population-based study conducted in China. The first study explored the relationship between hypertension and a healthy lifestyle score, which was derived from 5 factors: smoking, alcohol consumption, physical activity, body mass index and diet. The risk of hypertension tended to decrease with an increase in the healthy lifestyle score. Abdominal obesity is a risk factor for diabetes. The second study found that waist circumference (WC) had a significant linear relationship with haemoglobin A1c and fasting plasma glucose in both men and women. The optimal cutoff values of WC indicating a haemoglobin A1c of 6.5% in men and women are 85 cm and 86 cm, respectively.
Serum levels of FGF21, LCN-2, cystatin C and B2M were measured in the SHUN-CVD. The third study revealed that serum FGF21 was associated with systolic and diastolic blood pressure. A robust association was observed between FGF21 and hypertension. Additionally, CVDs are prevalent in patients with chronic kidney disease. The fourth study investigated the relationship between renal biomarkers and stroke risk. There were nearly a quarter (24%) of participants had high stroke risk. Serum LCN-2, cystatin C and B2M, independent of age, were associated with stroke risk.
MetS has been associated with neurological disorders and NfL is a neuro-axonal biomarker. The fifth study further examined the relationship between serum Nfl and MetS in US adults by using data from the National Health and Nutrition Examination Survey. The level of serum Nfl was increased in participants with MetS. NfL was significantly associated with both the number of MetS components and MetS severity score.
This thesis has several clinical implications. Firstly, there is an inverse relationship between the healthy lifestyle score and hypertension risk, which reinforces the need to address lifestyle to lower the risk of hypertension. Secondly, addressing abdominal obesity issue is beneficial to individuals with diabetes. WC cutoff values of 85 cm for men and 86 cm for women are appropriate for recommendation to undergo diabetes screening. Thirdly, FGF21 is a potential biomarker for assessing hypertension. Fourthly, serum LCN-2, cystatin C and B2M may be novel biomarkers for clinicians to assess stroke risk. Fifthly, measuring NfL may help identify neuro-axonal damage in patients with MetS and highlight the need for risk factor modification.published_or_final_versionMedicineDoctoralDoctor of Philosoph
Human lipocalin-2 variants : therapeutic evaluations
No full textLipocalin-2 is a proinflammatory protein that undergoes post-translational modification by polyamination and has unique structure-function dynamics. The presence of different lipocalin-2 variants exhibits varied expression patterns. In the present study, the role of human lipocalin-2 variants, including polyaminated lipocalin-2 (hLcn2), non-polyaminated lipocalin-2 (C87A), and highly polyaminated lipocalin-2 (R81E) in regulating neutrophil function and the formation of neutrophil extracellular traps (NETs) was investigated. The expression of distinctive human lipocalin-2 variants was examined in mouse models with obesity and/or cardiovascular dysfunctions. The therapeutical potential of targeting the different human lipocalin-2 variants was also explored.
The results demonstrated that C87A levels were significantly elevated in cardiac and epididymal white adipose tissue following a high-fat diet. Neutralization with an anti-C87A antibody effectively reduced NETs formation and downregulated key inflammatory chemokines,
I including CXCL2, which are critical for recruiting neutrophils via the CXCR2 chemokine receptor. Enhanced signaling through CXCR2 was observed in the presence of elevated C87A, correlating with increased neutrophil infiltration and NETosis, suggesting a direct link between lipocalin-2 variants and the regulation of neutrophil activity in inflammatory conditions.
Furthermore, the pathogenic role of C87A in models of obesity-induced hypertension and heart failure with preserved ejection fraction was assessed. Our results showed that modulation of C87A not only decreased neutrophil infiltration and NETosis but also mitigated the associated cardiovascular complications. Additionally, macrophage polarization was found to be protective against C87A-induced inflammation, while astrocytes in the brain may contribute to obesityinduced hypertension through the paracrine release of inflammatory factors, including lipocalin-2.
These findings highlight the complex interplay between lipocalin-2 variants, neutrophils, and inflammation, suggesting that targeting lipocalin-2 variant C87A may represent a novel therapeutic strategy to mitigate chronic inflammatory conditions and their cardiometabolic complications. This research underscores the importance of understanding the mechanisms underlying NETs formation and the potential for lipocalin-2 variants as therapeutic targets in managing obesity-related obesity and cardiometabolic diseases.published_or_final_versionPharmacology and PharmacyDoctoralDoctor of Philosoph