The challenge of determining the need for remediation following a wide-area biological release

Recovering from a biological attack is a complex process requiring the successful resolution of numerous challenges. The Interagency Biological Restoration Demonstration program is one of the first multiagency efforts to develop strategies and tools that could be effective following a wide-area release of B. anthracis spores. Nevertheless, several key policy issues and associated science and technology issues still need to be addressed. For example, more refined risk assessment and management approaches are needed to help evaluate "true" public health risk. Once the risk is understood, that information can be considered along with the types of characterization activities deemed necessary to determine whether the cost and time of decontamination are actually warranted. This commentary offers 5 recommendations associated with decision making regarding decontamination and clearance options that should accompany a comprehensive risk analysis leading to more effective risk management decisions. It summarizes some of the most important technological gaps that still need to be addressed to help decision makers in their objective of reducing health risks to an acceptable level. The risk management approach described should enable decision makers to improve credibility and gain public acceptance, especially when an adequate science and technology base is available to support the required decisions.     

The ArrayExpress gene expression database: a software engineering and implementation perspective

MOTIVATION: The lack of microarray data management systems and databases is still one of the major problems faced by many life sciences laboratories. While developing the public repository for microarray data ArrayExpress we had to find novel solutions to many non-trivial software engineering problems. Our experience will be both relevant and useful for most bioinformaticians involved in developing information systems for a wide range of high-throughput technologies. RESULTS: ArrayExpress has been online since February 2002, growing exponentially to well over 10,000 hybridizations (as of September 2004). It has been demonstrated that our chosen design and implementation works for databases aimed at storage, access and sharing of high-throughput data. AVAILABILITY: The ArrayExpress database is available at http://www.ebi.ac.uk/arrayexpress/. The software is open source. CONTACT: ugis@ebi.ac.uk.     

Harmonization: Developing Consistent Guidelines for Applying Mode of Action and Dosimetry Information to Cancer and Noncancer Risk Assessment

The 1983 book, Risk Assessment in the Federal Government: Managing the Process, recommended developing consistent inference guidelines for cancer risk assessment. Over the last 15 years, extensive guidance have been provided for hazard assessment for cancer and other endpoints. However, as noted in several recent reports, much less progress has occurred in developing consistent guidelines for quantitative dose response assessment methodologies. This paper proposes an approach for dose response assessment guided by consideration of mode of action (pharmacodynamics) and tissue dosimetry (pharmacokinetics). As articulated here, this systematic process involves eight steps in which available information is integrated, leading first to quantitative analyses of dose response behaviors in the test species followed by quantitative analyses of relevant human exposures. The process should be equally appropriate for both cancer and noncancer endpoints. The eight steps describe the necessary procedures for incorporating mechanistic data and provide multiple options based upon the mode of action by which the chemical causes the toxicity. Given the range of issues involved in developing such a procedure, we have simply sketched the process, focusing on major approaches for using toxicological data and on major options; many details remain to be filled in. However, consistent with the revised carcinogen risk assessment guidance (USEPA, 1996c), we propose a process that would ultimately utilize biologically based or chemical specific pharmacokinetic and pharmacodynamic models as the backbone of these analyses. In the nearer term, these approaches will be combined with analysis of data using more empirical models including options intended for use in the absence of detailed information. A major emphasis in developing any harmonized process is distinguishing policy decisions from those decisions that are affected by the quality and quantity of toxicological data. Identification of data limitations also identifies areas where further study should reduce uncertainty in the final risk evaluations. A flexible dose response assessment procedure is needed to insure that sound toxicological study results are appropriately used to influence risk management decision-making and to encourage the conduct of toxicological studies oriented toward application for dose response assessments.     

The development and status of Bt rice in China

Multiple lines of transgenic rice expressing insecticidal genes from the bacterium Bacillus thuringiensis (Bt) have been developed in China, posing the prospect of increases in production with decreased application of pesticides. We explore the issues facing adoption of Bt rice for commercial production in China. A body of safety assessment work on Bt rice has shown that Bt rice poses a negligible risk to the environment and that Bt rice products are as safe as non‐Bt control rice products as food. China has a relatively well‐developed regulatory system for risk assessment and management of genetically modified (GM) plants; however, decision‐making regarding approval of commercial production has become politicized, and two Bt rice lines that otherwise were ready have not been allowed to enter the Chinese agricultural system. We predict that Chinese farmers would value the prospect of increased yield with decreased use of pesticide and would readily adopt production of Bt rice. That Bt rice lines may not be commercialized in the near future we attribute to social pressures, largely due to the low level of understanding and acceptance of GM crops by Chinese consumers. Hence, enhancing communication of GM crop science‐related issues to the public is an important, unmet need. While the dynamics of each issue are particular to China, they typify those in many countries where adoption of GM crops has been not been rapid; hence, the assessment of these dynamics might inform resolution of these issues in other countries.     

The potential role of life cycle assessment in regulation of chemicals in the European union

Scope and Background  This paper presents the preliminary results from an ongoing feasibility study, investigating potential application of elements from the life cycle assessment (LCA) framework in European chemicals’ policy. Many policy areas affect manufacturing, marketing and use of chemicals. This article focuses on the general chemical legislation, especially issues related to regulatory risk assessment and subsequent decisions on risk reduction measures. Method  Current and upcoming chemical regulation has been reviewed and empirical knowledge has been gained from an ongoing case study and from dialogues with various stakeholders. Results and Discussion  LCAs are comparative and more holistic in view as compared to chemical risk assessments for regulatory purposes¹. LCAs may therefore potentially improve the basis for decisions between alternatives in cases where a risk assessment calls for risk reduction. In this process, LCA results might feed into a socio-economic analysis having similar objectives, but some methodological aspects related to system boundaries need to be sorted out. Life cycle impact assessment (LCIA) of toxic effects has traditionally been inspired by the more regulatory-orientated risk assessment approaches. However, the increasing need for regulatory priority setting and comparative/ cumulative assessments might in the future convey LCIA principles into the regulatory framework. The same underlying databases on inherent properties of chemicals are already applied in both types of assessment. Similarly, data on the use and exposure of chemicals are needed within both risk assessments and LCA, and the methodologies might therefore benefit from a joint ‘inventory’ database. Outlook  The final outcome of the feasibility study will be an implementation plan suggesting incorporation of core findings in future chemical regulation and related policy areas.     

Web portal to an image database for high-resolution three-dimensional reconstruction

The exponential increase of image data in high-resolution reconstructions by electron cryomicroscopy (cryoEM) has posed a need for efficient data management solutions in addition to powerful data processing procedures. Although relational databases and web portals are commonly used to manage sequences and structures in biological research, their application in cryoEM has been limited due to the complexity in accomplishing the dual tasks of interacting with proprietary software and simultaneously providing data access to users without database knowledge. Here, we report our results in developing web portal to SQL image databases used by the Image Management and Icosahedral Reconstruction System (IMIRS) to manage cryoEM images for subnanometer-resolution reconstructions. Fundamental issues related to the design and deployment of web portals to image databases are described. A web browser-based user interface was designed to accomplish data reporting and other database-related services, including user authentication, data entry, graph-based data mining, and various query and reporting tasks with interactive image manipulation capabilities. With an integrated web portal, IMIRS represents the first cryoEM application that incorporates both web-based data reporting tools and a complete set of data processing modules. Our examples should thus provide general guidelines applicable to other cryoEM technology development efforts.     

Developing Univariate Distributions from Data for Risk Analysis

The importance of fitting distributions to data for risk analysis continues to grow as regulatory agencies, like the Environmental Protection Agency (EPA), continue to shift from deterministic to probabilistic risk assessment techniques. The use of Monte Carlo simulation as a tool for propagating variability and uncertainty in risk requires specification of the risk model's inputs in the form of distributions or tables of data. Several software tools exist to support risk assessors in their efforts to develop distributions. However, users must keep in mind that these tools do not replace clear thought about judgments that must be made in characterizing the information from data. This overview introduces risk assessors to the statistical concepts and physical reasons that support important judgments about appropriate types of parametric distributions and goodness-of-fit. In the context of using data to improve risk assessment and ultimately risk management, this paper discusses issues related to the nature of the data (representativeness, quantity, and quality, correlation with space and time, and distinguishing between variability and uncertainty for a set of data), and matching data and distributions appropriately. All data analysis (whether “Frequentist” or “Bayesian” or oblivious to the distinction) requires the use of subjective judgment. The paper offers an iterative process for developing distributions using data to characterize variability and uncertainty for inputs to risk models that provides incentives for collecting better information when the value of information exceeds its cost. Risk analysts need to focus attention on characterizing the information appropriately for purposes of the risk assessment (and risk management questions at hand), not on characterization for its own sake.     

Standardisation of reference intervals: an Australasian view

The development of regional databases and doctors’ desktop programs that accept pathology results from different laboratories should improve patient care by allowing easy assessment of cumulative data. This has the potential to be unnecessarily confusing unless laboratories contributing to the databases provide standardised results and common reference intervals, where this is valid. The analytical methods that produce significantly different results need to be reported in a manner that avoids inappropriate interpretation.

The process of setting reference intervals requires an organisational structure which enables appropriate intervals to be set taking all relevant factors into account, including the opinions of expert clinicians. There must also be criteria for analytical agreement between the laboratories involved based on comparison studies using patient samples.

A network of QA groups across Australasia, with leadership from the AACB and RCPA, should be formed to share the ongoing work of defining reference intervals (RIs) for common tests, and reviewing them as the testing environment changes with the introduction of new techniques and instruments.

     

Regional Eco-Security Assessment Based on the Perspective of Complex System Science: A Case Study of Chongming in China

The objective of this study is to evaluate eco-security of Chongming in China and identify eco-security grades of the relevant subareas. In addition, the study aims to put forward the framework for a regional eco-security assessment system that is suitable for the analysis and evaluation of a man–land complex ecosystem. From the perspective of complex system science, this study puts forward the ANP-PRS-SENCE framework for a regional eco-security assessment. Based on the framework, a compressive assessment index system and a spatial variation assessment index system for Chongming's eco-security were established. Additionally, the eco-security threshold of Chongming was determined through the approach of system dynamics simulation. The assessment results show that in recent years the comprehensive score of eco-security has been on a gradual rise. With respect to the second-grade indices, the ecological risk and ecological protection indices are still relatively low. Therefore, in order to reduce the ecological risk, ecological construction needs to be strengthened and management measures need to be improved. The spatial variation assessment of eco-security shows that although the eco-security levels of most subareas remain between 0.3 and 0.6, regional variations are still quite obvious.     

Links between ecology and ecophilosophy,ethics and the requirements of environmental management

Abstract This paper concerns the ways that our philosophical attitudes to the environment can influence the appropriateness of methodologies for solving environmental problems. Sometimes a public perception is expressed that science takes scant regard of the concerns of the people affected. Is it possible for scientists and managers to respond to such concerns and still fulfil the logical and methodological rigour that their discipline demands? I believe we have to address fundamental issues of definitions and meaning before useful debate can occur among parties interested in environmental decision-making. Delving into the ideas behind our everyday practices of environmental management should promote re-evaluation of our beliefs, attitudes and concerns about nature. I examine environmental science from both ethical and managerial perspectives. I explore how our assumptions and attitudes might influence ecology, in particular issues raised by environmental impacts and conservation. The major points argued here are:

• 1 Any legal requirements of environmental investigations must be met, but perhaps we should act more in line with the spirit of legislation.
• 2 The managerial imperatives of environmental investigations need to be examined closely because of widely perceived problems with the use of science in impact assessment. We must change either our methods of assessment or the regulations and administration of environmental impact assessment (EIA).
• 3 Science is not paramount in the processes of environmental decision-making. We need to be aware of how psychosocial factors affect the ultimately political decisions about environmental problems.
• 4 Philosophy and ethics offer a range of perspectives that may benefit ecology. Scientists need to be aware of these just as they should be of their own leanings about how we treat nature.
• 5 Scientists need to translate social concerns or demands about the environment into properly defined scientific questions, and then study them as a matter of urgency.
• 6 Ecology needs to guide ecophilosophers and environmental ethicists as to how nature works, why we expect variability in ecosystems, what is naturalness, and other issues where a scientific understanding of nature has progressed beyond the point where these observers of ecology have so far taken inspiration.

     

The future of environmental DNA in ecology

The contributions of environmental DNA to ecology are reviewed, focusing on diet, trophic interactions, species distributions and biodiversity assessment. Environmental DNA has the potential to dramatically improve quantitative studies in these fields. Achieving this, however, will require large investments of time and money into developing the relevant databases, models, and software.     

Approaches to Quality Risk Management When Using Single-Use Systems in the Manufacture of Biologics

Biologics manufacturing technology has made great progress in the last decade. One of the most promising new technologies is the single-use system, which has improved the efficiency of biologics manufacturing processes. To ensure safety of biologics when employing such single-use systems in the manufacturing process, various issues need to be considered including possible extractables/leachables and particles arising from the components used in single-use systems. Japanese pharmaceutical manufacturers, together with single-use suppliers, members of the academia and regulatory authorities have discussed the risks of using single-use systems and established control strategies for the quality assurance of biologics. In this study, we describe approaches for quality risk management when employing single-use systems in the manufacturing of biologics. We consider the potential impact of impurities related to single-use components on drug safety and the potential impact of the single-use system on other critical quality attributes as well as the stable supply of biologics. We also suggest a risk-mitigating strategy combining multiple control methods which includes the selection of appropriate single-use components, their inspections upon receipt and before releasing for use and qualification of single-use systems. Communication between suppliers of single-use systems and the users, as well as change controls in the facilities both of suppliers and users, are also important in risk-mitigating strategies. Implementing these control strategies can mitigate the risks attributed to the use of single-use systems. This study will be useful in promoting the development of biologics as well as in ensuring their safety, quality and stable supply.KEY WORDS: biologics, manufacturing technology, quality risk management, regulatory science, single-use system     

Syncope: Assessment of risk and an approach to evaluation in the emergency department and urgent care clinic

Syncope is among the most frequent forms of transient loss of consciousness (TLOC), and is characterized by a relatively brief and self-limited loss of consciousness that by definition is triggered by transient cerebral hypoperfusion. Most often, syncope is caused by a temporary drop of systemic arterial pressure below that required to maintain cerebral function, but brief enough not to cause permanent structural brain injury. Currently, approximately one-third of syncope/collapse patients seen in the emergency department (ED) or urgent care clinic are admitted to hospital for evaluation. The primary objective of developing syncope/TLOC risk stratification schemes is to provide guidance regarding the immediate prognostic risk of syncope patients presenting to the ED or clinic; thereafter, based on that risk assessment physicians may be better equipped to determine which patients can be safely evaluated as outpatients, and which require hospital care. In general, the need for hospitalization is determined by several key issues: i) the patient''s immediate (usually considered 1 week to 1 month) mortality risk and risk for physical injury (e.g., falls risk), ii) the patient''s ability to care for him/herself, and iii) whether certain treatments inherently require in-hospital initiation (e.g., pacemaker implantation). However, at present no single risk assessment protocol appears to be satisfactory for universal application, and development of a consensus recommendation is an essential next step.     

美国、加拿大环境和健康风险管理方法

对目前美国和加拿大多个部门使用的风险评价与风险管理方法进行了全面回顾和综合分析,论述各种不同方法的特征,深入探讨各种管理方法的基础、利弊、使用经验,辨识环境、人类健康和职业健康风险综合方法中应该包含的要素,阐述风险管理目标的确定方法,以期为中国的环境风险管理提供经验。     

A dynamic assessment of water scarcity risk in the Lower Brahmaputra River Basin: An integrated approach

Many international river basins are likely to experience increasing water scarcity over the coming decades. This water scarcity is not rooted only in the limitation of resources, i.e. the shortage in the availability of freshwater relative to water demand, but also on social factors (e.g. flawed water planning and management approaches, institutional incapability to provide water services, unsustainable economic policies). Therefore, the assessment of water scarcity risks is not limited to the assessment of physical water supply and demand, but it requires also consideration of several socio-economic factors. In this study, we provide a comprehensive dynamic assessment of water scarcity risks for the Lower Brahmaputra river basin, a region where the hydrological impact of climate change is expected to be particularly strong and population pressure is high. The basin area of Brahmaputra River lies among four different countries: China, India, Bangladesh and Bhutan. For water scarcity assessment, we propose a novel integration of different approaches: (i) the assessment of water scarcity risk, considering complex social-ecological system; (ii) the analysis of dynamic behaviour of the system; (iii) exploration of participatory approach in which limited number of stakeholders identify the most relevant issues with reference to water scarcity risks and provide their preferences for the aggregation of risk assessment indicators. Results show that water scarcity risk is expected to slightly increase and to fluctuate remarkably as a function of the hazard signal. Social indicators show trends that can at least partially compensate the increasing trend of the drought index. The results of this study are intended to be used for contributing to planned adaptation of water resources systems, in Lower Brahmaputra River Basin.     

Application of life cycle assessment in the mining industry

Background, aim, and scope  

In spite of the increasing application of life cycle assessment (LCA) for engineering evaluation of systems and products, the application of LCA in the mining industry is limited. For example, a search in the Engineering Compendex database using the keywords “life cycle assessment” results in 2,257 results, but only 19 are related to the mining industry. Also, mining companies are increasingly adopting ISO 14001 certified environmental management systems (EMSs). A key requirement of ISO certified EMSs is continual improvement, which can be better managed with life cycle thinking. This paper presents a review of the current application of LCA in the mining industry. It discusses the current application, the issues, and challenges and makes relevant recommendations for new research to improve the current situation.     

生命周期评价方法在城市生活垃圾管理中的应用研究述评

结合城市生活垃圾管理系统特征,系统归纳基于生命周期评价(Life cycle assessment,LCA)方法的城市生活垃圾管理模型的发展现状,并对LCA方法在城市生活垃圾管理中的实践以及在我国开展城市生活垃圾管理LCA研究的应用前景进行评述。分析表明,LCA是城市生活垃圾管理领域的重要工具之一,基于LCA方法的城市生活垃圾管理模型在全生命周期环境影响评价与识别、处置工艺选择与改进、可持续生活垃圾管理决策支持等方面具有十分重要的应用价值。中国在本地化生活垃圾管理系统LCA模型开发、清单数据库和评价指标体系构建以及与其他研究方法集成等方面面临挑战。     

合成生物学伦理、法律与社会问题探讨

合成生物学是以基因组学、系统生物学知识和分子生物学技术为基础,综合了科学与工程的一门新兴交叉学科。它使生命科学和生物技术研发进入了以人工设计、合成自然界中原本不曾出现的人造生命体系,以及对这些人工体系进行体内、体外优化,或利用这些人造生命体系研究自然生命规律为目标的新时代。然而,合成生物学研究在迅速发展、表现出巨大潜力和应用前景的同时,也引发了社会各界对相关社会、伦理、安全,以及知识产权等问题的重视与讨论。就世界各国针对合成生命对传统意义上生命概念的挑战、合成生物学产品存在的潜在风险危害、合成生物学研究的风险评估与监管等问题进行回顾综述和相关探讨。     

Risk analysis: an overview

Risk analysis increasingly is considered as an integral part of the environmental management decision-making process. Risk, defined as the probability of occurrence of a particular adverse effect on human health or the environment, should not be confounded with hazard, defined as a source of potential injury independent of occurrence. Risk analysis has to be followed by risk management. Some opponents of risk analysis make the reproach that the science used in risk analysis is immature and consequently that the entire process in laden with hidden value judgments. Attempts to overcome these critics are increasingly based on the use of robust biologic data the final considered values system being efficacy-based, efficiency-based or equity-based. Globalization has brought with it new problems, and there is an urgent need to improve risk analysts; to increase its public acceptability and to establish consensus regarding solutions to global environmental problems. In this context biologic-based models and biomarkers hold, the greatest promise for improving risk assessment. These considerations are illustrated by a few examples, also pertaining to low-dose extrapolation and to the problem of thresholds for carcinogenesis. Future directions for development are evoked.