The transborder economic region of Hong Kong - Shenzhen

纪念香港回归、地理学研究成果的“ 特辑”A few transborder regions have appeared in the 1970s as a consequence of international di-vision of labour in manufacturing arising from globalization of economic activities. The border-ing cities of Hong Kong and Shenzhen belong to different ideologies and systems of gover-nance, yet they have since the late 1970s gradually developed into a highly interrelated trans-border economic region. Such development has promoted economic growth of Shenzhen and deepened the structural transformation of Hong Kong into a higher status in international trade, shipping, and finance. The mutual causative transborder development in the past decade had largely been initiated and participated by private investors following the rule of the mar-ket. After 1997, with the return of Hong Kong to China,transborder cooperation is expected to receive more government attention and achieve promotion. Of course the continue existence of a demarcation is crucial to transborder cooperation and will benefit both places. The case of Hong Kong-Shenzhen is different from other transborder regions such as the Singapore Trian-gle. 本文以70年代末中國改革開放以來香港-深圳這兩個分屬不同社會制度的城市的發展和緊密結合而形成跨境城市經濟區為個案研究對象,總結兩者各自的城市發展歷史,分析兩地在過往10余年間的跨境發展特征及相互影響。一方面深圳借助于香港資本流入等因素發展成為現代化的大都市;另一方面香港跨境向深圳、珠江三角洲經濟腹地擴散,促進了其產業升級和國際貿易、金融和航運中心地位的鞏固。過往10多年香港-深圳跨境的區域發展是由市場規范的、自發和民間促成的。隨著“九七”香港回歸祖國,這一跨境城市經濟區的發展應由兩地政府積極、主動地參與和管理。同時,港深管理線的存在及其完整性對保持和促進這一跨境城市經濟區的發展是至關重要的。published_or_final_versio

Characterising QT interval prolongation in early clinical development: a case study with methadone

Recently, we have shown how pharmacokinetic-pharmacodynamic (PKPD) modelling can be used to assess the probability of QTc interval prolongation both in dogs and humans. A correlation between species has been identified for a drug-specific parameter, making it possible to prospectively evaluate non-clinical signals. Here, we illustrate how nonclinical data on methadone can be used to support the evaluation of prodromic drug effects in humans. ECG and drug concentration data from safety pharmacology study in dogs were analysed using nonlinear mixed effects modelling. The slope of the PKPD model describing the probability of QT interval prolongation was extrapolated from dogs to humans and subsequently combined with methadone pharmacokinetic data as input for clinical trial simulations. Concentration vs. time profiles were simulated for doses between 5 and 500 mg. Predicted peak concentrations in humans were then used as reference value to assess the probability of an increase in QTc interval of ≥ 5 and ≥10 ms. Point estimates for the slope in dogs suggested low probability of ≥10 ms prolongation in humans. However, an effect of approximately 5 ms increase is predicted when accounting for the 90% credible intervals the drug-specific parameter in dogs. In addition, our analysis show that understanding of interspecies differences in drug disposition is required to accurately predict the QT prolonging effects in humans. Extrapolation of the effects of parent compound may not be sufficient to describe the increase in QT interval observed after administration of methadone in humans. Assessment of the contribution of enantioselective metabolism and active metabolites is critical

Ambient-aware continuous care through semantic context dissemination

Background: The ultimate ambient-intelligent care room contains numerous sensors and devices to monitor the patient, sense and adjust the environment and support the staff. This sensor-based approach results in a large amount of data, which can be processed by current and future applications, e. g., task management and alerting systems. Today, nurses are responsible for coordinating all these applications and supplied information, which reduces the added value and slows down the adoption rate. The aim of the presented research is the design of a pervasive and scalable framework that is able to optimize continuous care processes by intelligently reasoning on the large amount of heterogeneous care data. Methods: The developed Ontology-based Care Platform (OCarePlatform) consists of modular components that perform a specific reasoning task. Consequently, they can easily be replicated and distributed. Complex reasoning is achieved by combining the results of different components. To ensure that the components only receive information, which is of interest to them at that time, they are able to dynamically generate and register filter rules with a Semantic Communication Bus (SCB). This SCB semantically filters all the heterogeneous care data according to the registered rules by using a continuous care ontology. The SCB can be distributed and a cache can be employed to ensure scalability. Results: A prototype implementation is presented consisting of a new-generation nurse call system supported by a localization and a home automation component. The amount of data that is filtered and the performance of the SCB are evaluated by testing the prototype in a living lab. The delay introduced by processing the filter rules is negligible when 10 or fewer rules are registered. Conclusions: The OCarePlatform allows disseminating relevant care data for the different applications and additionally supports composing complex applications from a set of smaller independent components. This way, the platform significantly reduces the amount of information that needs to be processed by the nurses. The delay resulting from processing the filter rules is linear in the amount of rules. Distributed deployment of the SCB and using a cache allows further improvement of these performance results

Statistical Techniques Complement UML When Developing Domain Models of Complex Dynamical Biosystems

Computational modelling and simulation is increasingly being used to complement traditional wet-lab techniques when investigating the mechanistic behaviours of complex biological systems. In order to ensure computational models are fit for purpose, it is essential that the abstracted view of biology captured in the computational model, is clearly and unambiguously defined within a conceptual model of the biological domain (a domain model), that acts to accurately represent the biological system and to document the functional requirements for the resultant computational model. We present a domain model of the IL-1 stimulated NF-κB signalling pathway, which unambiguously defines the spatial, temporal and stochastic requirements for our future computational model. Through the development of this model, we observe that, in isolation, UML is not sufficient for the purpose of creating a domain model, and that a number of descriptive and multivariate statistical techniques provide complementary perspectives, in particular when modelling the heterogeneity of dynamics at the single-cell level. We believe this approach of using UML to define the structure and interactions within a complex system, along with statistics to define the stochastic and dynamic nature of complex systems, is crucial for ensuring that conceptual models of complex dynamical biosystems, which are developed using UML, are fit for purpose, and unambiguously define the functional requirements for the resultant computational model