Why every national deep-geological-isolation program needs a long-term science & technology component

The objective of this paper is to set down the rationale for a separate Science & Technology (S&T) Program within every national deep-geological-isolation program. The fundamental rationale for such a Program is to provide a dedicated focus for longer-term science and technology activities that ultimately will benefit the whole repository mission. Such a Program, separately funded and with a dedicated staff (separate from the ''mainline'' activities to develop the repository, the surface facilities, and the transportation system), can devote itself exclusively to the development and management of a long-term science and technology program. Broad experience in governments worldwide has demonstrated that line offices are unlikely to be able to develop and sustain both the appropriate longer-term philosophy and the specialized skills associated with managing longer-term science and technology projects. Accomplishing both of these requires a separate dedicated program office with its own staff

NRC Seismic Design Margins Program Plan

Recent studies estimate that seismically induced core melt comes mainly from earthquakes in the peak ground acceleration range from 2 to 4 times the safe shutdown earthquake (SSE) acceleration used in plant design. However, from the licensing perspective of the US Nuclear Regulatory Commission, there is a continuing need for consideration of the inherent quantitative seismic margins because of, among other things, the changing perceptions of the seismic hazard. This paper discusses a Seismic Design Margins Program Plan, developed under the auspices of the US NRC, that provides the technical basis for assessing the significance of design margins in terms of overall plant safety. The Plan will also identify potential weaknesses that might have to be addressed, and will recommend technical methods for assessing margins at existing plants. For the purposes of this program, a general definition of seismic design margin is expressed in terms of how much larger that the design basis earthquake an earthquake must be to compromise plant safety. In this context, margin needs to be determined at the plant, system/function, structure, and component levels. 14 refs., 1 fig

Recommendations for probabilistic seismic hazard analysis: Guidance on uncertainty and use of experts

Probabilistic Seismic Hazard Analysis (PSHA) is a methodology that estimates the likelihood that various levels of earthquake-caused ground motion will be exceeded at a given location in a given future time period. Due to large uncertainties in all the geosciences data and in their modeling, multiple model interpretations are often possible. This leads to disagreement among experts, which in the past has led to disagreement on the selection of ground motion for design at a given site. In order to review the present state-of-the-art and improve on the overall stability of the PSHA process, the U.S. Nuclear Regulatory Commission (NRC), the U.S. Department of Energy (DOE), and the Electric Power Research Institute (EPRI) co-sponsored a project to provide methodological guidance on how to perform a PSHA. The project has been carried out by a seven-member Senior Seismic Hazard Analysis Committee (SSHAC) supported by a large number other experts. The SSHAC reviewed past studies, including the Lawrence Livermore National Laboratory and the EPRI landmark PSHA studies of the 1980`s and examined ways to improve on the present state-of-the-art. The Committee`s most important conclusion is that differences in PSHA results are due to procedural rather than technical differences. Thus, in addition to providing a detailed documentation on state-of-the-art elements of a PSHA, this report provides a series of procedural recommendations. The role of experts is analyzed in detail. Two entities are formally defined-the Technical Integrator (TI) and the Technical Facilitator Integrator (TFI)--to account for the various levels of complexity in the technical issues and different levels of efforts needed in a given study

HUMAN DISEASE FROM RADON EXPOSURES: THE IMPACT OF ENERGY CONSERVATION IN RESIDENTIAL BUILDINGS

The level of radon and its daughters inside conventional buildings is often higher than the ambient background level. Interest in conserving energy is motivating homeowners and builers to reduce ventilation and hence to increase the concentration of indoor generated air contaminants, including radon. It is unliekly that the current radiation levels in conventional homes and buildings from radon daughters could account for a significant portion of the lung cancer rate in non-smokers. However, it is likely that some increased lung cancer risk would result from increased radon exposures; hence, it is prudent not to allow radon concentrations to rise significantly. There are several ways to implement energy conservation measures without increasing risks

Adverse Drug Reactions Related Hospital Admissions in Persons Aged 60 Years and over, The Netherlands, 1981–2007: Less Rapid Increase, Different Drugs

Background: Epidemiologic information on time trends of Adverse Drug Reactions (ADR) and ADR-related hospitalizations is scarce. Over time, pharmacotherapy has become increasingly complex. Because of raised awareness of ADR, a decrease in ADR might be expected. The aim of this study was to determine trends in ADR-related hospitalizations in the older Dutch population. Methodology and Principal Findings: Secular trend analysis of ADR-related hospital admissions in patients ≥60 years between 1981 and 2007, using the National Hospital Discharge Registry of the Netherlands. Numbers, age-specific and age-adjusted incidence rates (per 10,000 persons) of ADR-related hospital admissions were used as outcome measures in each year of the study. Between 1981 and 2007, ADR-related hospital admissions in persons ≥60 years increased by 143%. The overall standardized incidence rate increased from 23.3 to 38.3 per 10,000 older persons. The increase was larger in males than in females. Since 1997, the increase in incidence rates of ADR-related hospitalizations flattened (percentage annual change 0.65%), compared to the period 1981-1996 (percentage annual change 2.56%). Conclusion/Significance: ADR-related hospital admissions in older persons have shown a rapidly increasing trend in the Netherlands over the last three decades with a temporization since 1997. Although an encouraging flattening in the increasing trend of ADR-related admissions was found around 1997, the incidence is still rising, which warrants sustained attention to this problem

Inappropriate prescribing and adverse drug events in older people

Inappropriate prescribing (IP) in older patients is highly prevalent and is associated with an increased risk of adverse drug events (ADEs), morbidity, mortality and healthcare utilisation. Consequently, IP is a major safety concern and with changing population demographics, it is likely to become even more prevalent in the future. IP can be detected using explicit or implicit prescribing indicators. Theoretically, the routine clinical application of these IP criteria could represent an inexpensive and time efficient method to optimise prescribing practice. However, IP criteria must be sensitive, specific, have good inter-rater reliability and incorporate those medications most commonly associated with ADEs in older people. To be clinically relevant, use of prescribing appropriateness tools must translate into positive patient outcomes, such as reduced rates of ADEs. To accurately measure these outcomes, a reliable method of assessing the relationship between the administration of a drug and an adverse clinical event is required. The Naranjo criteria are the most widely used tool for assessing ADE causality, however, they are often difficult to interpret in the context of older patients. ADE causality criteria that allow for the multiple co-morbidities and prescribed medications in older people are required. Ultimately, the current high prevalence of IP and ADEs is unacceptable. IP screening criteria need to be tested as an intervention to assess their impact on the incidence of ADEs in vulnerable older patients. There is a role for IP screening tools in everyday clinical practice. These should enhance, not replace good clinical judgement, which in turn should be based on sound pharmacogeriatric training

Informatic Tools and Approaches in Postmarketing Pharmacovigilance Used by FDA

The safety profile of newly approved drugs and therapeutic biologics is less well developed by pre-marketing clinical testing than is the efficacy profile. The full safety profile of an approved product is established during years of clinical use. For nearly 40 years, the FDA has relied on the voluntary reporting of adverse events by healthcare practitioners and patients to help establish the safety of marketed products. Epidemiologic studies, including case series, secular trends, case-control and cohort studies, are used to supplement the investigation of a safety signal. Ideally, active surveillance systems would supplement the identification and exploration of safety signals. The FDA has implemented a number of initiatives to help identify safety problems with drugs and continues to evaluate their efforts

Predicting hospital stay, mortality and readmission in people admitted for hypoglycaemia: prognostic models derivation and validation

Aims/hypothesis: Hospital admissions for hypoglycaemia represent a significant burden on individuals with diabetes and have a substantial economic impact on healthcare systems. To date, no prognostic models have been developed to predict outcomes following admission for hypoglycaemia. We aimed to develop and validate prediction models to estimate risk of inpatient death, 24 h discharge and one month readmission in people admitted to hospital for hypoglycaemia. Methods: We used the Hospital Episode Statistics database, which includes data on all hospital admission to National Health Service hospital trusts in England, to extract admissions for hypoglycaemia between 2010 and 2014. We developed, internally and temporally validated, and compared two prognostic risk models for each outcome. The first model included age, sex, ethnicity, region, social deprivation and Charlson score (‘base’ model). In the second model, we added to the ‘base’ model the 20 most common medical conditions and applied a stepwise backward selection of variables (‘disease’ model). We used C-index and calibration plots to assess model performance and developed a calculator to estimate probabilities of outcomes according to individual characteristics. Results: In derivation samples, 296 out of 11,136 admissions resulted in inpatient death, 1789/33,825 in one month readmission and 8396/33,803 in 24 h discharge. Corresponding values for validation samples were: 296/10,976, 1207/22,112 and 5363/22,107. The two models had similar discrimination. In derivation samples, C-indices for the base and disease models, respectively, were: 0.77 (95% CI 0.75, 0.80) and 0.78 (0.75, 0.80) for death, 0.57 (0.56, 0.59) and 0.57 (0.56, 0.58) for one month readmission, and 0.68 (0.67, 0.69) and 0.69 (0.68, 0.69) for 24 h discharge. Corresponding values in validation samples were: 0.74 (0.71, 0.76) and 0.74 (0.72, 0.77), 0.55 (0.54, 0.57) and 0.55 (0.53, 0.56), and 0.66 (0.65, 0.67) and 0.67 (0.66, 0.68). In both derivation and validation samples, calibration plots showed good agreement for the three outcomes. We developed a calculator of probabilities for inpatient death and 24 h discharge given the low performance of one month readmission models. Conclusions/interpretation: This simple and pragmatic tool to predict in-hospital death and 24 h discharge has the potential to reduce mortality and improve discharge in people admitted for hypoglycaemia

Sodium fast reactor safety and licensing research plan. Volume II.

Expert panels comprised of subject matter experts identified at the U.S. National Laboratories (SNL, ANL, INL, ORNL, LBL, and BNL), universities (University of Wisconsin and Ohio State University), international agencies (IRSN, CEA, JAEA, KAERI, and JRC-IE) and private consultation companies (Radiation Effects Consulting) were assembled to perform a gap analysis for sodium fast reactor licensing. Expert-opinion elicitation was performed to qualitatively assess the current state of sodium fast reactor technologies. Five independent gap analyses were performed resulting in the following topical reports: (1) Accident Initiators and Sequences (i.e., Initiators/Sequences Technology Gap Analysis), (2) Sodium Technology Phenomena (i.e., Advanced Burner Reactor Sodium Technology Gap Analysis), (3) Fuels and Materials (i.e., Sodium Fast Reactor Fuels and Materials: Research Needs), (4) Source Term Characterization (i.e., Advanced Sodium Fast Reactor Accident Source Terms: Research Needs), and (5) Computer Codes and Models (i.e., Sodium Fast Reactor Gaps Analysis of Computer Codes and Models for Accident Analysis and Reactor Safety). Volume II of the Sodium Research Plan consolidates the five gap analysis reports produced by each expert panel, wherein the importance of the identified phenomena and necessities of further experimental research and code development were addressed. The findings from these five reports comprised the basis for the analysis in Sodium Fast Reactor Research Plan Volume I