Assay platform for clinically relevant metallo-beta-lactamases

Metallo-β-lactamases (MBLs) are a growing threat to the use of almost all clinically used β-lactam antibiotics. The identification of broad-spectrum MBL inhibitors is hampered by the lack of a suitable screening platform, consisting of appropriate substrates and a set of clinically relevant MBLs. We report procedures for the preparation of a set of clinically relevant metallo-β-lactamases (i.e., NDM-1 (New Delhi MBL), IMP-1 (Imipenemase), SPM-1 (São Paulo MBL), and VIM-2 (Verona integron-encoded MBL)) and the identification of suitable fluorogenic substrates (umbelliferone-derived cephalosporins). The fluorogenic substrates were compared to chromogenic substrates (CENTA, nitrocefin, and imipenem), showing improved sensitivity and kinetic parameters. The efficiency of the fluorogenic substrates was exemplified by inhibitor screening, identifying 4-chloroisoquinolinols as potential pan MBL inhibitors

Remote Data Retrieval for Bioinformatics Applications: An Agent Migration Approach

Some of the approaches have been developed to retrieve data automatically from one or multiple remote biological data sources. However, most of them require researchers to remain online and wait for returned results. The latter not only requires highly available network connection, but also may cause the network overload. Moreover, so far none of the existing approaches has been designed to address the following problems when retrieving the remote data in a mobile network environment: (1) the resources of mobile devices are limited; (2) network connection is relatively of low quality; and (3) mobile users are not always online. To address the aforementioned problems, we integrate an agent migration approach with a multi-agent system to overcome the high latency or limited bandwidth problem by moving their computations to the required resources or services. More importantly, the approach is fit for the mobile computing environments. Presented in this paper are also the system architecture, the migration strategy, as well as the security authentication of agent migration. As a demonstration, the remote data retrieval from GenBank was used to illustrate the feasibility of the proposed approach

Biomedical informatics and translational medicine

Biomedical informatics involves a core set of methodologies that can provide a foundation for crossing the "translational barriers" associated with translational medicine. To this end, the fundamental aspects of biomedical informatics (e.g., bioinformatics, imaging informatics, clinical informatics, and public health informatics) may be essential in helping improve the ability to bring basic research findings to the bedside, evaluate the efficacy of interventions across communities, and enable the assessment of the eventual impact of translational medicine innovations on health policies. Here, a brief description is provided for a selection of key biomedical informatics topics (Decision Support, Natural Language Processing, Standards, Information Retrieval, and Electronic Health Records) and their relevance to translational medicine. Based on contributions and advancements in each of these topic areas, the article proposes that biomedical informatics practitioners ("biomedical informaticians") can be essential members of translational medicine teams

Embodied uncertainty: living with complexity and natural hazards

In this paper, we examine the concept of embodied uncertainty by exploring multiple dimensions of uncertainty in the context of risks associated with extreme natural hazards. We highlight a need for greater recognition, particularly by disaster management and response agencies, of uncertainty as a subjective experience for those living at risk. Embodied uncertainty is distinguished from objective uncertainty by the nature of its internalisation at the individual level, where it is subjective, felt and directly experienced. This approach provides a conceptual pathway that sharpens knowledge of the processes that shape how individuals and communities interpret and contextualise risk. The ways in which individual characteristics, social identities and lived experiences shape interpretations of risk are explored by considering embodied uncertainty in four contexts: social identities and trauma, the co-production of knowledge, institutional structures and policy and long-term lived experiences. We conclude by outlining the opportunities that this approach presents, and provide recommendations for further research on how the concept of embodied uncertainty can aid decision-making and the management of risks in the context of extreme natural hazards

Decision-Making: Preventing Miscommunication and Creating Shared Meaning Between Stakeholders

The effective management and response to either volcanic eruptions or (often prolonged) periods of heightened unrest, is fundamentally dependent upon effective relationships and communication between science advisors, emergency managers and key decision makers. To optimise the effectiveness of the scientific contribution to effective prediction and management decision making, it is important for science advisors or scientific advisory bodies to be cognisant of the many different perspectives, needs and goals of the diverse organisations involved in the response. Challenges arise for scientists as they may need to be embedded members of the wider response multi-agency team, rather than independent contributors of essential information. Thus they must add to their competencies an understanding of the different roles, responsibilities, and needs of each member organisation, such that they can start to provide information implicitly rather than in response to explicit requests. To build this shared understanding, the team situational awareness (understanding of the situation in time and space), and the wider team mental model (a representation of the team functions and responsibilities), requires participating in a response environment together. Facilitating the availability of this capability has training and organizational development implications for scientific agencies and introduces a need for developing new inter-agency relationships and liaison mechanisms well before a volcanic crisis occurs. In this chapter, we review individual and team decision making, and the role of situational awareness and mental models in creating “shared meaning” between agencies. The aim is to improve communication and information sharing, as well as furthering the understanding of the impact that uncertainty has upon communication and ways to manage this. We then review personal and organisational factors that can impact response and conclude with a brief review of methods available to improve future response capability, and the importance of protocols and guidelines to assist this in a national or international context.</p