213-Bi-DOTATATE for Targeted Alpha Therapy in Neuroendocrine Tumours

Targeted alpha therapy (TAT) is promising for improvement of current peptide receptor radionuclide therapy for patient with metastatic neuroendocrine tumours. Due to the high LET of alpha particles, the possibility to cause double strand breaks in the DNA of a tumour cell is much higher than after therapy using beta particle emitters. At the same time, healthy tissues can be spared because of the short path length of alpha particles. _213_ Bismuth (_213_ Bi, an alpha emitter with a half-life of 46 min) was eluted from a _225_ Ac/_213_ Bi generator. _213_ Bi was attached to a peptide via a chelator, in our case a somatostatin analogue with the DOTA chelator, DOTA-Tyr3-octreotate (DOTATATE). In this thesis, _213_ Bi-DOTATATE was used for TAT to investigate whether it is superior compared to DOTATATE labelled with beta particle emitters, like _177_ Lu-DOTATATE for treatment of neuroendocrine tumours with somatostatin receptor expression. The stability of _213_ Bi-DOTATATE was investigated; the labelled peptide showed high stability up to 2 h after labelling. _213_ Bi-DOTATATE showed higher therapeutic efficacy in vitro compared to _177_ Lu-DOTATATE; a 5x more tumour cells killing potency was found. _213_ Bi-DOTATATE prolonged survival in xenografted mice with different tumour models with varying somatostatin receptor density and tumour size. Potential renal toxicity could be managed by renal protectant L-lysine application. Furthermore, biodistribution was imaged by a special SPECT camera dedicated to small animals imaging. Overall, _213_ Bi-DOTATATE showed to be promising for TAT for treatment of neuroendocrine tumours with somatostatin expression

Waiting for signalized crossing or walking to footbridge/underpass? Examining the effect of weather using stated choice experiment with panel mixed random regret minimization approach

It is a challenging task for pedestrians to cross a road with multiple traffic lanes and busy traffic. Many footbridges and underpasses have been built in the urban area of metropolitan cities such as Hong Kong to resolve the problem of vehicle-pedestrian conflict. To maximize the utilization and benefit of the installation of such crossing facilities, it is crucial to understand the choice behaviour of pedestrians. Although many studies have examined pedestrian walking behaviour and preference towards crossing facilities, the influence of ratio of perceived values between waiting and walking time on the choice of crossing is not explored. In addition, individual perception and choice may vary with the environmental conditions, which has not been fully accounted for in existing studies. Exposure to extremely hot weather, crowded walkways, and roadside traffic emissions are not favoured. In this study, a stated choice experiment is developed to examine the relationship between possible influencing factors and the crossing choices of pedestrians in Hong Kong. In addition, a regret-based panel mixed multinomial logit approach is adopted to model the choice, accounting for the effects of unobserved heterogeneity and panel data. The results indicate that the choice decision of pedestrians is more sensitive to an increase in waiting time at signalized crossings than to an increase in walking time to access footbridges and underpasses. These findings shed light on future urban and transport planning strategies to improve the walking environment and promote walkability

COVID-19, community response, public policy, and travel patterns: a tale of Hong Kong

The COVID-19 outbreak has necessitated a critical review of urban transportation and its role in society against the backdrop of an exogenous shock. This article extends the transportation literature regarding community responses to the COVID-19 pandemic and what lessons can be obtained from the case of Hong Kong in 2020. Individual behavior and collective responsibility are considered crucial to ensure both personal and community wellbeing in a pandemic context. Trends in government policies, the number of infectious cases, and community mobility are examined using multiple data sources. The mobility changes that occurred during the state of emergency are revealed by a time-series analysis of variables that measure both the epidemiological severity level and government stringency. The results demonstrate a high response capability of the local government, inhabitants, and communities. Communities in Hong Kong are found to have reacted faster than the implementation of health interventions, whereas the government policies effectively reduced the number of infection cases. The ways in which community action are vital to empower flexible and adaptive community responses are also explored. The results indicate that voluntary community involvement constitutes a necessary condition to help inform and reshape future transport policy and response strategies to mitigate the pandemic

Epigenetic Dysregulation in Laryngeal Squamous Cell Carcinoma

Laryngeal carcinoma is a common head and neck cancer with poor prognosis. Patients with laryngeal carcinoma usually present late leading to the reduced treatment efficacy and high rate of recurrence. Despite the advance in the use of molecular markers for monitoring human cancers in the past decades, there are still no reliable markers for use to screen laryngeal carcinoma and follow the patients after treatment. Epigenetics emerged as an important field in understanding the biology of the human malignancies. Epigenetic alterations refer to the dysregulation of gene, which do not involve the alterations of the DNA sequence. Major epigenetic changes including methylation imbalance, histone modification, and small RNA dysregulation could play a role in the development of human malignancies. Global epigenetic change is now regarded as a molecular signature of cancer. The characteristics and behavior of a cancer could be predicted based on the specific epigenetic pattern. We here provide a review on the understanding of epigenetic dysregulation in laryngeal carcinoma. Further knowledge on the initiation and progression of laryngeal carcinoma at epigenetic level could promote the translation of the knowledge to clinical use

Comparison of post-treatment plasma EBV DNA with nasopharyngeal biopsy in patients after radical (chemo) radiotherapy for non-metatatic nasopharyngeal cancer

This journal suppl. entitled: Proceedings of the American Society for Radiation Oncology 56th Annual Meeting, ASTRO's 56th Annual Meeting ... 2014Oral Scientific SessionPURPOSE/OBJECTIVE(S): Random nasopharyngeal biopsy after completion of intensity-modulated radiation therapy (IMRT) for non-metastatic nasopharyngeal cancer (NPC) is routinely practiced in Hong Kong to confirm local remission. Plasma EBV DNA is proven an accurate marker for NPC. We carried out a prospective study comparing the correlation between post-IMRT nasopharyngeal biopsy and EBV DNA, to investigate if EBV DNA can substitute biopsy to confirm local remission. MATERIALS/METHODS: Patients with non-metastatic NPC treated with definitive (chemo) IMRT diagnosed between January 2011 and March 2013 were recruited. After baseline workup ...postprin

Student Evaluation of Lecturer Performance Among Private University Students

The evaluation of lecturer performance at the end of the semester is widely practicedby learning institutions and universities. The results of the evaluations are beneficial in understanding the areas of possible improvement for the lecturer. The purpose of this study is to identify the factors and predictors of lecturer performance among undergraduates in a private university in Malaysia using the existing questionnaire. A total of 223 respondents were recruited using multistage sampling.The results of this study showed that lecturer and tutor characteristics (r = 0.722, p < 0.01), subject characteristics (r = 0.699, p < 0.01), the studentship (r = 0.472, p < 0.01), and learning resources and facilities (r = 0.650, p < 0.01) were positively correlated with overall lecturer performance. Stepwise hierarchical regression was used to determine the predictors of overall lecturer performance among the students. The results of the final model showed that lecturer and tutor characteristics, subject characteristics, and learning resources and facilities explained 61.9% of the variance in overall lecturer performance among students (F = 118.732, p < 0.01). Knowing the predictors of overall lecturer performance would help the lecturer and university identify the specific areas for improving the performance of the lecturer. Key words: Lecturer and tutor characteristics; Subject characteristics; Learning resources and facilities; Overall performanc

Understanding and promoting oral health of Indonesian domestic helpers in Hong Kong

Includes bibliographical references (p. 44).published_or_final_versio

A Preliminary Psychometric Investigation of a Chinese Version of the Engaged Teachers Scale (C-ETS)

This study examines the psychometric properties of a Chinese version of the Engaged Teacher Scale (C-ETS). A translated questionnaire with 16 items was administered to a sample of 341 primary and secondary school teachers in Hong Kong. A series of confirmatory factor analyses were performed to assess the construct, convergent, and discriminant validity of the scale in alternative models. Results provide support for a second-order model with teacher engagement as an overarching construct with four hypothesized dimensions: emotional engagement, cognitive engagement, social engagement (students), and social engagement (colleagues). The C-ETS provides a useful measure for teacher engagement in Chinese societies. Contributions and limitations of the study are discussed

MicroRNA 744-3p promotes MMP-9-mediated metastasis by simultaneously suppressing PDCD4 and PTEN in laryngeal squamous cell carcinoma

MicroRNA controls cancer invasion by governing the expression of gene regulating migration and invasion. Here, we reported a novel regulatory pathway controlled by miR-744-3p, which enhanced expression of matrix metallopeptidase 9 (MMP-9) in laryngeal squamous cell carcinoma (LSCC). We profiled the differential micoRNA expression pattern in LSCC cell lines and normal epithelial cultures derived from the head and neck mucosa using microRNA microarray. MiR-7-1-3p, miR-196a/b and miR-744-3p were expressed differentially in the LSCC cell lines. Subsequent validation using real-time PCR revealed that high miR-744-3p level was positively correlated with regional lymph node metastasis of LSCC. Real-time cellular kinetic analysis showed that suppressing miR-744-3p could inhibit migration and invasion of LSCC cell lines and reduce the number of lung metastatic nodules in nude mice modules. In silico analysis revealed that miR-744-3p targeted 2 distinct signaling cascades which eventually upregulated MMP-9 expression in LSCC. First, miR-744-3p could suppress programmed cell death 4 (PDCD4), a direct suppressor of NF-κB (p65). PDCD4 could also prevent AKT activation and suppress MMP-9 expression. Further, suppressing miR-744-3p expression could restore phosphatase and tensin homolog (PTEN) expression. PTEN could inhibit AKT activation and inhibit MMP-9 expression in LSCC cells. The results revealed that suppressing miR-744-3p was effective to inhibit LSCC metastasis by inactivating AKT/mTOR and NF-κB (p65) signaling cascade. Targeting miR-744-3p could be a valuable therapeutic intervention to suppress the aggressiveness of LSCC.published_or_final_versio