System-wide Approaches Research Articles

The zebrafish embryo model in environmental risk assessment—applications beyond acute toxicity testing

The use of fish embryos is not regulated by current legislations on animal welfare and is therefore considered as a refinement, if not replacement of animal experiments. Fish embryos represent an attractive model for environmental risk assessment of chemicals since they offer the possibility to perform small-scale, high-throughput analyses. Beyond their application for determining the acute toxicity, fish embryos are also excellent models for studies aimed at the understanding of toxic mechanisms and the indication of possible adverse and long-term effects. Therefore, we have reviewed the scientific literature in order to indicate alternative applications of the fish embryo model with focus on embryos of the zebrafish. The analysis of the mode of action is important for the risk assessment of environmental chemicals and can assist in indicating adverse and long-term effects. Toxicogenomics present a promising approach to unravel the potential mechanisms. Therefore, we present examples of the use of zebrafish embryos to study the effect of chemicals on gene and protein patterns, and the potential implications of differential expression for toxicity. The possible application of other methods, such as kinase arrays or metabolomic profiling, is also highlighted. Furthermore, we show examples of toxicokinetic studies (bioconcentration, ABC transporters) and discuss limitations that might be caused by the potential barrier function of the chorion. Finally, we demonstrate that biomarkers of endocrine disruption, immune modulation, genotoxicity or chronic toxicity could be used as indicators or predictors of sub-acute and long-term effects. The zebrafish embryo represents a model with an impressive range of possible applications in environmental sciences. Particularly, the adaptation of molecular, system-wide approaches from biomedical research is likely to extend its use in ecotoxicology. Challenges for future research are (1) the identification of further suitable molecular markers as indicators of the mode of action, (2) the establishment of strong links between (molecular) effects in short-term assays in embryos and long-term (toxic) effects on individuals, (3) the definition of limitations of the model and (4) the development of tests that can be used for regulatory purposes.

Interventions to Increase Influenza Vaccination Rates in Veterans With Spinal Cord Injuries and Disorders

Objective: To increase the percentage of veterans with spinal cord injuries and disorders (SCI&D) who receive annual influenza vaccinations.Design: A repeated measures quality improvement project using several integrated evidence-based interventions.Setting: 23 Veterans Affairs (VA) SCI Centers.Patients: Veterans with SCI&D average age = 57.3 years (range 21-102 y).Interventions: Patient reminder letters and education; provider reminders and posters; computerized clinical reminders for vaccination targeted to SCI&D; standing orders. Main outcome measures: Patient selfreported vaccination status.Results: Baseline vaccination rate was 33% in fiscal year (FY) 2001. The percentage of veterans with SCI&D who reported receiving vaccinations increased from 62.5% in year 1 (FY2002) to 67.4% in FY2003 (P =0.004); for individuals younger than 50 years of age, rates increased from 50% to 54%. Predictors of vaccination were age 65 years of age or older, VA health care visit in past year, nonsmoker, believing vaccination is important, having a health condition that may contribute to respiratory complications, and self-reported influenza in prior year.Conclusions: Vaccination rates were higher than baseline and higher than reported for other high-risk groups. Interventions that incorporate system-wide approaches plus patient and provider education and reminders were moderately effective in increasing vaccination rates. Targeting younger persons, smokers, and those who do not use VA care may further improve rates.

System-wide adoption of health promotion practices by schools: evaluation of a telephone and mail-based dissemination strategy in Australia

Schools can potentially benefit from system-wide approaches to the dissemination of health promotion practices. This intervention study undertaken in the Hunter Region of NSW, Australia, used a pre-post design to assess whether a phone and mail intervention dissemination strategy was associated with an increase in the proportion of 218 primary schools undertaking eight health promotion practices. Health promotion practices addressed the prevention of harm associated with five agreed health issues-smoking, nutrition, playground safety, asthma and infectious diseases. The study also assessed acceptability of the dissemination strategy to schools, cost and whether intervention schools' characteristics were associated with uptake of health promotion practices. Compared to baseline a significant improvement in prevalence was observed at both 1 and 2 year follow-up for seven of the eight health promotion practices addressed. The greatest improvement occurred in the first year of the project. There was a greater uptake of the practice of providing information regarding passive smoking in urban schools. The dissemination strategy was found to have a cost per adopted practice of 121 Australian dollars and to be acceptable to the large majority (>90%) of schools. The results suggest that the dissemination strategy may represent a relatively low cost method of enhancing health promotion practices in schools and of monitoring such practices. Further research addressing the methodological issues of this study is needed to confirm these findings.

Patient safety and medication errors

The morbidity and mortality of drug-related problems has most recently been estimated to cost $177.4 billion annually within the United States alone. Empirical investigations have also suggested that almost one-fifth of all medical errors are drug-related within hospital settings, with over half of these being of a preventable nature. As such, minimizing medication errors has emerged as a priority area to ensure patient safety within healthcare systems worldwide, as several nations have implemented broad initiatives to improve the medication use system. Due to the numerous complexities involved, multifaceted and systemwide approaches to redesigning processes are most often advocated. Given the importance of appropriate medication use in achieving optimal patient outcomes, this paper addresses the various nomenclature and taxonomies of error within healthcare as well as the incidence, risk factors, causes, and prevention of medication errors.

Energy management for commercial servers

Servers: high-end, multiprocessor systems running commercial workloads, have typically included extensive cooling systems and resided in custom-built rooms for high-power delivery. Recently, as transistor density and demand for computing resources have rapidly increased, even these high-end systems face energy-use constraints. Commercial-server energy management now focuses on conserving power in the memory and microprocessor subsystems. Because their workloads are typically structured as multiple application programs, system-wide approaches are more applicable to multiprocessor environments in commercial servers than techniques that primarily apply to single-application environments, such as those based on compiler optimizations.

Understanding and preventing adverse drug events.

Adverse drug events affect approximately 10% of patients in hospitals and result in increased rates of morbidity and mortality. These adverse events extend hospital stays an estimated 1.7 to 2.2 days and increase costs by approximately $3,200 for patients who are affected. Nurses play a key role in reducing risks of adverse drug events. Through purposeful, planned actions, nurses can help to curtail unexpected costs and can further promote safe patient care. Specific problem areas of the drug delivery system resulting in high numbers of significant (lethal or severe) drug events can be targeted for precautionary actions. An interdisciplinary "safety net" can be developed and maintained to reduce these events. Guidelines are recommended for system-wide approaches to prevention and continuous quality improvement activities.

The human firm in the natural environment: a socio-economic analysis of its behavior

New realities are leading an increasing number of businesses to discard their old managerial perspectives and practices with regard to the natural environment. As desirable as the new approaches are, the environmental behavior (pollution, pollution prevention, etc.) of these firms cannot be explained by the neoclassical model. Thus, this paper develops a socio-economic model of the firm's environmental behavior that incorporates managerial, social, environmental, and ethical realities not found in the neoclassical model. In contrast to short-term oriented, opportunistic approaches, managements are increasingly setting high environmental goals, integrating environmental management with other aspects of management, developing environmentally oriented strategies that harmonize economic and environmental interests, and utilizing system-wide approaches along with socially responsible decision making. This cannot be explained by the neoclassical model in which the firm's environmental behavior is an outcome of economic incentives from (1) product and resource markets, and (2) regulators. The socio-economic model adds four important new elements: (1) the firm's internal organizational capability; (2) environmental opportunities; (3) society's environmental concerns, awareness, and demands; and (4) influences from extra-firm institutions. Therefore, the firm's environmental behavior is an outcome not only of economic incentives but of (1) the firm's capacity to take advantage of opportunities, and (2) the external social influences on it.

Neighborhood Influences on Travel Behavior and Availability Constraints

Traditionally, transportation demand studies have, for the most part, viewed modal choice in terms of an aggregate system-wide function. However, it seems reasonable to expect that the travel decision may be influenced by a composite of factors that include not only availability conditions, but determinants relating to neighborhood characteristics and peer-group pressures. In this paper, supply-side constraints on availability were used to segment the market and logit probabilistic choice models were fitted to each segment. It was found that inducements to individuals to alter their modal choice must consider not only cost factors and standard demographics, but also peer-group (class) constraints. System-wide approaches will fail to consider these important demand considerations.