How can health care organisations make and justify decisions about risk reduction? Lessons from a cross-industry review and a health care stakeholder consensus development process

Interventions to reduce risk often have an associated cost. In UK industries decisions about risk reduction are made and justified within a shared regulatory framework that requires that risk be reduced as low as reasonably practicable. In health care no such regulatory framework exists, and the practice of making decisions about risk reduction is varied and lacks transparency. Can health care organisations learn from relevant industry experiences about making and justifying risk reduction decisions? This paper presents lessons from a qualitative study undertaken with 21 participants from five industries about how such decisions are made and justified in UK industry. Recommendations were developed based on a consensus development exercise undertaken with 20 health care stakeholders. The paper argues that there is a need in health care to develop a regulatory framework and an agreed process for managing explicitly the trade-off between risk reduction and cost. The framework should include guidance about a health care specific notion of acceptable levels of risk, guidance about standardised risk reduction interventions, it should include regulatory incentives for health care organisations to reduce risk, and it should encourage the adoption of an approach for documenting explicitly an organisation’s risk position

Of disasters and dragon kings: a statistical analysis of nuclear power incidents and accidents

We perform a statistical study of risk in nuclear energy systems. This study provides and analyzes a data set that is twice the size of the previous best data set on nuclear incidents and accidents, comparing three measures of severity: the industry standard International Nuclear Event Scale, the Nuclear Accident Magnitude Scale of radiation release, and cost in U.S. dollars. The rate of nuclear accidents with cost above 20 MM 2013 USD, per reactor per year, has decreased from the 1970s until the present time. Along the way, the rate dropped significantly after Chernobyl (April 1986) and is expected to be roughly stable around a level of 0.003, suggesting an average of just over one event per year across the current global fleet. The distribution of costs appears to have changed following the Three Mile Island major accident (March 1979). The median cost became approximately 3.5 times smaller, but an extremely heavy tail emerged, being well described by a Pareto distribution with parameter α = 0.5–0.6. For instance, the cost of the two largest events, Chernobyl and Fukushima (March 2011), is equal to nearly five times the sum of the 173 other events. We also document a significant runaway disaster regime in both radiation release and cost data, which we associate with the “dragon-king” phenomenon. Since the major accident at Fukushima (March 2011) occurred recently, we are unable to quantify an impact of the industry response to this disaster. Excluding such improvements, in terms of costs, our range of models suggests that there is presently a 50% chance that (i) a Fukushima event (or larger) occurs every 60–150 years, and (ii) that a Three Mile Island event (or larger) occurs every 10–20 years. Further—even assuming that it is no longer possible to suffer an event more costly than Chernobyl or Fukushima—the expected annual cost and its standard error bracket the cost of a new plant. This highlights the importance of improvements not only immediately following Fukushima, but also deeper improvements to effectively exclude the possibility of “dragon-king” disasters. Finally, we find that the International Nuclear Event Scale (INES) is inconsistent in terms of both cost and radiation released. To be consistent with cost data, the Chernobyl and Fukushima disasters would need to have between an INES level of 10 and 11, rather than the maximum of 7

Could ethanol-induced alterations in the expression of glutamate transporters in testes contribute to the effect of paternal drinking on the risk of abnormalities in the offspring?

It has been known that a preconception paternal alcoholism impacts adversely on the offspring but the mechanism of the effect is uncertain. Several findings suggest that there are signalling systems in testis that are analogous to those known to be altered by alcoholism in brain. We propose that chronic alcohol affects these systems in a manner similar to that in brain. Specifically, we hypothesise that excessive alcohol may disturb glutamatergic-like signalling in testis by increasing expression of the glutamate transporter GLAST (EAAT1). We discuss ways how to test the hypothesis as well as potential significance of some of the tests as tools in the diagnostics of chronic alcoholism

Uncertainty handling in fault tree based risk assessment: State of the art and future perspectives

YesRisk assessment methods have been widely used in various industries, and they play a significant role in improving the safety performance of systems. However, the outcomes of risk assessment approaches are subject to uncertainty and ambiguity due to the complexity and variability of system behaviour, scarcity of quantitative data about different system parameters, and human involvement in the analysis, operation, and decision-making processes. The implications for improving system safety are slowly being recognised; however, research on uncertainty handling during both qualitative and quantitative risk assessment procedures is a growing field. This paper presents a review of the state of the art in this field, focusing on uncertainty handling in fault tree analysis (FTA) based risk assessment. Theoretical contributions, aleatory uncertainty, epistemic uncertainty, and integration of both epistemic and aleatory uncertainty handling in the scientific and technical literature are carefully reviewed. The emphasis is on highlighting how assessors can handle uncertainty based on the available evidence as an input to FTA

Characterization of the human renal Na+-sulphate cotransporter gene ( NAS1) promoter

Sulphate (SO42-) plays an essential role during growth, development, and cellular metabolism. Recently, we have isolated the human renal Na+-SO42- cotransporter (hNaSi-1) that is implicated in the regulation of serum SO42- levels. To gain an insight into hNaSi-1 regulation, our aims were to clone and characterize functionally the hNaSi-1 gene (NAS1) promoter. We PCR-amplified 3742 bp of the NAS1 5'-flanking region, which is 64% AT-rich and contains numerous putative cis-acting elements. The NAS1 transcription start site was mapped to 25 bp upstream from the translation start site. NAS1 promoter truncations fused to luciferase gene constructs transfected into renal LLC-PK1, MDCK and OK cells allowed us to establish that the first 169 bp of the NAS1 promoter are sufficient for basal transcription. Furthermore, the NAS1 promoter conferred responsiveness to the polycyclic aromatic hydrocarbon 3-methylcholanthrene (3-MC), but not to thyroid hormone (T-3) or vitamin D [1,25-(OH)(2)D-3]. Site-directed mutagenesis of the NAS1 promoter identified a functional xenobiotic response element at -2,052, which conferred 3-MC responsiveness. The human NAS1 gene promoter is not responsive to Vitamin D or T-3, unlike the mouse Nas1 promoter with which it shares similar to40% sequence similarity, but is transactivated by 3-MC, suggesting that the control of renal SO42- reabsorption via the regulation of NAS1 transcription may be important for maintaining the sulphation potential for kidney polycyclic aromatic hydrocarbon metabolism

The mouse sulfate anion transporter gene Sat1 (Slc26a1): Cloning, tissue distribution, gene structure, functional characterization, and transcriptional regulation by thyroid hormone

Sulfate (SO42-) is required for bone/cartilage formation and cellular metabolism. sat-1 is a SO42- anion transporter expressed on basolateral membranes of renal proximal tubules, and is suggested to play an important role in maintaining SO42- homeostasis. As a first step towards studying its tissue-specific expression, hormonal regulation, and in preparation for the generation of knockout mice, we have cloned and characterized the mouse sat-1 cDNA (msat-1), gene (sat1; Slc26a1) and promoter region. msat-1 encodes a 704 amino acid protein (75.4 kDa) with 12 putative transmembrane domains that induce SO42- (also oxalate and chloride) transport in Xenopus oocytes. msat-1 mRNA was expressed in kidney, liver, cecum, calvaria, brain, heart, and skeletal muscle. Two distinct transcripts were expressed in kidney and liver due to alternative utilization of the first intron, corresponding to an internal portion of the 5'-untranslated region. The Sa1 gene (similar to6 kb) consists of 4 exons. Its promoter is similar to52% G+C rich and contains a number of well-characterized cis-acting elements, including sequences resembling hormone responsive elements T3REs and VDREs. We demonstrate that Sat1 promoter driven basal transcription in OK cells was stimulated by tri-iodothyronine. Site-directed mutagenesis identified an imperfect T3RE at -454-bp in the Sat1 promoter to be responsible for this activity. This study represents the first characterization of the structure and regulation of the Sat1 gene encoding a SO42-/chloride/oxalate anion transporter