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Melatonin is a human neurotransmitter and plant signalling metabolite that perceives and directs plant metabolism. The mechanisms of melatonin action in plants remain undefined. We hypothesized that roots have a melatonin-specific receptor and/or transporter that can respond to melatonin-mediating pharmaceuticals. To test this hypothesis Arabidopsis seedlings were grown with melatonin pharmaceutical receptor agonists: ramelteon and tasimelteon, and/or antagonists: luzindole and 4-P-PDOT. Ramelteon was found both to mimic and competitively inhibit melatonin metabolism in plants. Due to the higher selectivity of ramelteon for the MT1 receptor type in humans, a sequence homology search for MT1 in Arabidopsis identified the rhomboid-like protein 7 (RBL7). In physiological studies, Arabidopsis rbl7 mutants were less responsive to ramelteon and melatonin. Quantum dot visualizations of the effects of ramelteon on melatonin binding to root cell membranes revealed a potential mechanism. We propose that RBL7 is a melatonin-interacting protein that directs root architecture and growth in a mechanism that is responsive to environmental factors.

Object-oriented programming has come forth as an important programming paradigm in the 1980's. As more and more people practice object-oriented programming, the subject of how to design and develop a system towards an object-oriented implementation becomes important. There is, therefore, a general demand for a design method which is specially developed for object-oriented programming. The theme of this thesis is to develop such a design method. The thesis starts off with a comprehensive background on object-oriented programming and how it differs from traditional programming. It also gives a detailed analysis of why existing design methods are inadequate for object-oriented programming. The thesis then presents the design method which has been developed in this research. The different stages of the design method and the various tasks that have to be performed at each stage are discussed thoroughly. The design method also embeds a design description language which allows system designers to communicate with each other during the design phase and this is also talked about in the thesis. Inheritance is regarded as an important feature found in object-oriented programming. A design method without substantial support for inheritance is considered to be incomplete. Therefore, a mechanism which is called the inheritance factorisation process is developed to assist system designers to construct class hierarchies in object-oriented programming. The mechanism has a formal model which ensures its correctness. The details of the formal model and the issues concerning how to use the mechanism forms a crucial part of this thesis. To examine the performance of the inheritance factorisation process, a factorisation engine is implemented and experiments have been carried out. To illustrate how the design method is used in system designs, two case studies have been carried out and are presented in this thesis. The result of this thesis is a design method which guides system designers to organise the design activities towards an object-oriented implementation. It also forms the basis of future work which will lead to a computer-aided software engineering environment for object-oriented programming.

Object-oriented programming has come forth as an important programming paradigm in the 1980's. As more and more people practice object-oriented programming, the subject of how to design and develop a system towards an object-oriented implementation becomes important. There is, therefore, a general demand for a design method which is specially developed for object-oriented programming. The theme of this thesis is to develop such a design method. The thesis starts off with a comprehensive background on object-oriented programming and how it differs from traditional programming. It also gives a detailed analysis of why existing design methods are inadequate for object-oriented programming. The thesis then presents the design method which has been developed in this research. The different stages of the design method and the various tasks that have to be performed at each stage are discussed thoroughly. The design method also embeds a design description language which allows system designers to communicate with each other during the design phase and this is also talked about in the thesis. Inheritance is regarded as an important feature found in object-oriented programming. A design method without substantial support for inheritance is considered to be incomplete. Therefore, a mechanism which is called the inheritance factorisation process is developed to assist system designers to construct class hierarchies in object-oriented programming. The mechanism has a formal model which ensures its correctness. The details of the formal model and the issues concerning how to use the mechanism forms a crucial part of this thesis. To examine the performance of the inheritance factorisation process, a factorisation engine is implemented and experiments have been carried out. To illustrate how the design method is used in system designs, two case studies have been carried out and are presented in this thesis. The result of this thesis is a design method which guides system designers to organise the design activities towards an object-oriented implementation. It also forms the basis of future work which will lead to a computer-aided software engineering environment for object-oriented programming.

Traditional Chinese Medicine (TCM) has become increasingly popular around the world, and has been accepted by people not only in China and Southeast Asia, but also in Western countries. Despite its historic role in the Chinese society, there has been limited research on exploring the nature of TCM practitioner-patient interactions in the Chinese context. As indicated by a major study regarding the Hong Kong context1, there is a need to investigate the role of TCM practitioner and promote interdisciplinary research to ensure safety and synergy of TCM and Western medicine in primary care. This study aims to address this gap by investigating the nature of TCM consultations and their communication patterns in Hong Kong. Based on 10 h of conversations (in Cantonese) between TCM practitioners and their patients in the diagnostic interviews, the study explored how the doctor-patient relationship was negotiated in the course of the consultation, while both the TCM practitioners and the patients were constantly trying to manage and maintain common ground. Particular attention had been paid to the identification of specific linguistic and discourse strategies that TCM practitioners had employed to establish doctor-patient rapport, so that a better understanding of patient-centred care in the TCM context could be obtained. The participants were recruited from a local university operated clinic which shared the characteristic of TCM practitioners in Hong Kong. A range of linguistic strategies that TCM practitioners used to deliver patient-centred care have been identified. These strategies are also helpful in shaping a joint decision-making process that will lead to better patient understanding and compliance with the doctors’ treatments. This study demonstrates empirically how TCM practitioners utilize a range of linguistic resources and communication strategies to shape the ongoing discourse so that their patients can have a better understanding of their illnesses. For an example, it is found that TCM practitioners and their patients were constantly trying to manage and maintain common ground by using a range of grammatical markers, including sentence-final particles (SFPs) and discourse markers (DMs), to negotiate the epistemic commitment so that the patient would have good compliance with the practitioner’s suggested treatment. It is also observed that various types of interrogatives have been used by the TCM practitioners to elicit information from the patients as well as to encourage them to talk and make a response. Furthermore, it is found that TCM practitioners would deliberately enquire about the patients’ everyday experiences because what they eat, do, and encounter all have an important impact on their body conditions. By exploring into the patients’ daily routines in the social talk, the practitioner can help maintain and promote the overall balance of the patient’s body, and help them monitor and enhance their health conditions by modifying their daily habits and behaviours. With the adoption of these linguistic and communication strategies, the TCM practitioners are shown to have placed the patients’ needs as their top priority. Previous studies in the field have already proved that co-construction of the treatment plan between the doctor and the patient is extremely important, and that a patient-centred approach can largely reduce adverse events leading to avoidable patient harm. The specific strategies identified in the current study can enhance the TCM practitioners’ communication with patients, creating an environment that will surely optimise safety for both patients and clinicians.

PurposeTo compare transarterial chemoembolization (TACE), transarterial radioembolization using Yttrium-90 (TARE), and transarterial ethanol ablation (TEA) for huge hepatocellular carcinoma (HCC) in treatment responses and long-term survival outcomes.Materials and MethodsIn this retrospective study approved by institutional committee, inclusion criteria were tumour ≥ 10 cm, newly diagnosed, treatment naïve, Child A, Performance Score 0 or 1, no venous invasion or extrahepatic disease on contrast-enhanced CT or MRI. There were 107 patients (Supportive Care [SC] 17, TACE 54, TARE 17, TEA 19). Survival outcomes of SC and TACE were compared (TACE selected as benchmark for transarterial treatments). Tumour response and overall survival (OS) of the three groups were compared.ResultsOS of TACE (vs. SC) was significantly longer (9.9 [5.9, 24.1] months versus 2.8 [1.5, 10.2], p = 0.001). Complete response of TEA was significantly better (TEA 10/19 [52.6%] versus TARE 2/17 [12.5%], p = 0.013, versus TACE 9/54 [16.7%], p = 0.002). OS of TEA (vs. TACE) was significantly longer (21.6 [12, 41] months versus 9.9 [5.9, 24.1], p = 0.014, hazard ratio 0.6 (0.3, 1). OS of TEA (vs. TARE) was longer (21.6 [12, 41] months versus 11.9 [7, 28.7], p = 0.082, hazard ratio 0.6 (0.3, 1.3) in favour of TEA).ConclusionIn patients with huge HCC, transarterial treatment as represented by TACE had a survival benefit over supportive care. In this retrospective analysis, TEA was associated with better tumour response and survival outcome as compared to TACE or TARE; therefore, transarterial treatment could be useful for prolonging patient survival, and TEA could be a preferred option.

In parts of Asia, about 10% of the population have chronic hepatitis B virus (HBV) infection, and cancer patients who are HBV carriers are frequently complicated by HBV reactivation while receiving cytotoxic chemotherapy. The condition may result in varying degrees of liver damage, causing disruption in chemotherapy and compromising the patients' prognosis. With the increasing use of chemotherapy paralleling the rise in breast cancer incidence, the occurrence of HBV reactivation is likely to further increase. Recent reports have suggested that the anti-viral agent, lamivudine, may reduce HBV reactivation and its associated morbidity. However, most studies are based on small series of lymphoma patients, while information on the other high risk population, namely breast cancer patients, has been lacking. In this study, we studied the role of lamivudine in preventing HBV reactivation and its associated morbidity in breast cancer patients with chronic HBV infection who were planned for chemotherapy. Two groups were studied. One group consisted of 31 patients who received 'prophylactic lamivudine' prior to and until 8 weeks after discontinuing chemotherapy. The other comprised of 61 historical controls who underwent chemotherapy without prophylactic lamivudine. The outcomes, in terms of the efficacy of lamivudine in reducing the incidence of HBV reactivation, and diminishing morbidity during chemotherapy were compared. The results revealed that in the prophylactic lamivudine group, despite a significantly higher proportion receiving anthracyclines, there was significantly fewer incidences of hepatitis (12.9 vs. 59.0%, p < 0.001), less HBV reactivation (6.5. vs. 31.1%, p=0.008), and less disruption of chemotherapy (16.1% vs. 45.9%, p=0.006). We conclude that prophylactic lamivudine significantly reduces the incidence of HBV reactivation and the overall morbidity of breast cancer patients undergoing chemotherapy.

Purpose We aimed to validate the Multinational Association for Supportive Care in Cancer (MASCC) risk index, and compare it with the Talcott model and artificial neural network (ANN) in predicting the outcome of febrile neutropenia in a Chinese population. Methods We prospectively enrolled adult cancer patients who developed febrile neutropenia after chemotherapy and risk classified them according to MASCC score and Talcott model. ANN models were constructed and temporally validated in prospectively collected cohorts. Results From October 2005 to February 2008, 227 consecutive patients were enrolled. Serious medical complications occurred in 22% of patients and 4% died. The positive predictive value of low risk prediction was 86% (95% CI = 81–90%) for MASCC score ≥ 21, 84% (79–89%) for Talcott model, and 85% (78–93%) for the best ANN model. The sensitivity, specificity, negative predictive value, and misclassification rate were 81%, 60%, 52%, and 24%, respectively, for MASCC score ≥ 21; and 50%, 72%, 33%, and 44%, respectively, for Talcott model; and 84%, 60%, 58%, and 22%, respectively, for ANN model. The area under the receiver-operating characteristic curve was 0.808 (95% CI = 0.717–0.899) for MASCC, 0.573 (0.455–0.691) for Talcott, and 0.737 (0.633–0.841) for ANN model. In the low risk group identified by MASCC score ≥ 21 (70% of all patients), 12.5% developed complications and 1.9% died, compared with 43.3%, and 9.0%, respectively, in the high risk group ( p  < 0.0001). Conclusions The MASCC risk index is prospectively validated in a Chinese population. It demonstrates a better overall performance than the Talcott model and is equivalent to ANN model.

This study aimed to evaluate and compare the biodistribution properties of three transarterial Lipiodol-based therapeutic regimens in human hepatocellular carcinoma (HCC). In this prospective study with 13 patients randomly allocated to one of three study groups, each of the patients received transcatheter intra-arterial administration into a solitary HCC with one of three different Lipiodol-based formulations: Lipiodol-ethanol mixture (LEM; Group A), Lipiodol alone (Group B), and Lipiodol and gelatin pledgets (Group C). With the use of radioactive iodine-131-labeled Lipiodol, each group was assessed for (1) pattern of Lipiodol accumulation in the lungs within the first 2 weeks as evaluated by single-photon emission computed tomography and (2) decomposition of Lipiodol formulation within the first 2 weeks as evaluated by radioactivity detected in peripheral blood and urine. The degree of Lipiodol retention in the tumor within the first 4 weeks was evaluated with CT. No statistically significant difference in Lipiodol accumulation in the lungs was detected among the three groups. However, the peak accumulation in the lungs was delayed 3 days for Group A compared to Groups B and C. The degree of Lipiodol retention within the tumor in Group A was significantly greater than that in Groups B and C on day 14 ( p  = 0.014) and day 28 ( p  = 0.013). This study showed that LEM is associated with a greater embolic effect in intrahepatic HCC at 4 weeks, and a comparable degree of lung shunting and decomposition rates, compared with ethanol-free Lipiodol formulations.