Do Faster Rescues Save More Lives

The primary mission of search and rescue (SAR) is the saving of lives. To assess SAR operations from a planning perspective, one must draw a connection between operations and the number of lives saved. Our approach is to model the probability that an incident results in at least one fatality, given the response time between the time of incident occurrence and time of rescue. We show that incidents involving air crashes, capsizing, foundering, grounding and other/unknown types of incidents tended to have higher probabilities of fatalities as the response time became higher. However, other emergency types did not exhibit the same overall tendency as these did. These statistical results do not prove causality between faster response times and lower fatality incidence for the above-mentioned emergency types. They can be used, however, for estimating the average number of fatalities for a given distribution of response time, and ultimately the marginal savings in lives for a change in the mix of resources and locations.     

The Impact of Cytochrome P450 2E1-Dependent Metabolic Variance on a Risk-Relevant Pharmacokinetic Outcome in Humans

Risk assessments include assumptions about sensitive subpopulations, such as the fraction of the general population that is sensitive and the extent that biochemical or physiological attributes influence sensitivity. Uncertainty factors (UF) account for both pharmacokinetic (PK) and pharmacodynamic (PD) components, allowing the inclusion of risk-relevant information to replace default assumptions about PK and PD variance (uncertainty). Large numbers of human organ donor samples and recent advances in methods to extrapolate in vitro enzyme expression and activity data to the intact human enable the investigation of the impact of PK variability on human susceptibility. The hepatotoxicity of trichloroethylene (TCE) is mediated by acid metabolites formed by cytochrome P450 2E1 (CYP2E1) oxidation, and differences in the CYP2E1 expression are hypothesized to affect susceptibility to TCE's liver injury. This study was designed specifically to examine the contribution of statistically quantified variance in enzyme content and activity on the risk of hepatotoxic injury among adult humans. We combined data sets describing (1) the microsomal protein content of human liver, (2) the CYP2E1 content of human liver microsomal protein, and (3) the in vitro Vmax for TCE oxidation by humans. The 5th and 95th percentiles of the resulting distribution (TCE oxidized per minute per gram liver) differed by approximately sixfold. These values were converted to mg TCE oxidized/h/kg body mass and incorporated in a human PBPK model. Simulations of 8-hour inhalation exposure to 50 ppm and oral exposure to 5 micro g TCE/L in 2 L drinking water showed that the amount of TCE oxidized in the liver differs by 2% or less under extreme values of CYP2E1 expression and activity (here, selected as the 5th and 95th percentiles of the resulting distribution). This indicates that differences in enzyme expression and TCE oxidation among the central 90% of the adult human population account for approximately 2% of the difference in production of the risk-relevant PK outcome for TCE-mediated liver injury. Integration of in vitro metabolism information into physiological models may reduce the uncertainties associated with risk contributions of differences in enzyme expression and the UF that represent PK variability.     

The Logical Difference Between Prevention and Treatment

The authors have spent 2 1/2 years investigating the process of change in family systems presenting with addictive symptoms in one or more of their members. The context of this research has been the systemic family therapy of more than 36 families in a hospital based drug and alcohol service. Emergent from this research is evidence of potentially destructive effects upon families and addicts who present requesting help, by referring them to programmes which are educative or preventative in nature. The case will be put for a clear distinction to be made between the functions of ‘prevention’ and ‘treatment’ in multi-disciplinary teams in addiction services (and by implication other community health services); and for establishing a more rigorous intake system based upon such a distinction and designed to respond more appropriately to presenting requests by potential users of such a service.     

Toward a resilient complex adaptive system view of business models

This paper employs the theory of resilient complex adaptive systems (RCAS) to offer a versatile and universal foundation for the concept of a business model that facilitates connections between prior works while enabling future exploration with a common language. The proposed business model construct is developed by first exploring the field of systems to highlight how the concept of an RCAS can be employed to provide a more robust conceptualization of a business model than previous constructs. A thematic analysis of the literature is then conducted to translate the fundamental requirements of an RCAS into the business model context. This system view is inherently abstraction tolerant and provides a foundation for both academic research and practical applications. Specifically, it addresses two key gaps in the business model literature. First, the comprehensive nature of the system model naturally calls out important aspects of business models that have been largely ignored in the literature. Second, the construct provides a comprehensive means to connect the work of business model scholars and practitioners outlined in more than 150 studied articles, highlighting how each earlier research effort has employed a construct that is actually part of a grander whole.